JP4170198B2 - Cosmetic composition - Google Patents

Description

  The present invention relates to a novel cosmetic composition.

  In the development and production of cosmetics, the effects attached to the cosmetics include (1) whitening effect to prevent or improve skin darkening caused by spots, freckles and ultraviolet rays, (2) rough skin, dry skin, Moisturizing effect to prevent or improve acne, pimples, anti-inflammatory effect and skin modulation prevention or improvement effect represented by antibacterial effect, (3) wrinkles, dullness, skin softness or elasticity decrease, skin sagging, skin The above three items of the anti-skin aging effect for preventing or improving the decrease in immune function and the like are general. The cosmetics manufacturing industry usually develops and manufactures cosmetics with one or more of the above three items. As a result of technological progress in the cosmetics manufacturing industry to date, the above (2) can be achieved relatively easily. For this reason, the item (2) above is usually attached to current cosmetics, and consumers tend to recognize that they are usually attached to cosmetics. is there. Therefore, people who use cosmetics on a daily basis tend to place particular importance on (1) and (3), and cosmetic manufacturers have cosmetics with high effects on (1) or (3). There is a strong demand from consumers for the development and manufacture of

As a method for attaching the whitening effect of (1), the most common method is to add a whitening agent. Examples of whitening agents include (a) a substance that suppresses the activity of tyrosinase involved in the production of melanin pigment, (b) a substance that suppresses the activity of cells that produce melanin pigment, and (c) melanin excretion based on turnover promotion. To promote cell division, examples include substances that activate cell division of basal cells, and examples include active ingredients such as ascorbic acid or derivatives thereof, arbutin, plant extracts, microbial cell extracts, and fermentation products. (Non-Patent Document 1). In recent years, the process of proliferation or activation of pigment cells themselves and the process of expression and activation of tyrosinase itself has been actively studied, and various factors have been discovered and substances that affect these factors have been developed. (Non-patent document 2, Patent document 1, Patent document 2). In this way, various whitening agents have been developed so far, but for the purpose of developing cosmetics with higher whitening effect, more effective whitening agents have been eagerly desired. Development is continuing.
FRAGRANCE JOURNAL Special issue, No.14, 1995, 118-126 FRAGRANCE JOURNAL Special issue, No.18, 2003, 9-15, 22-29, 42-49, 50-55 JP 2003-183175 A JP 2003-194809 A

(3) As a method of attaching the effect of preventing skin aging, dry protection by applying a moisturizing agent, UV protection by applying an UV absorber or UV scattering agent, blood circulation promotion, application of an astringent, etc. have been used for a long time. In addition, in recent years, protection against oxidation caused by ultraviolet rays and atmospheric substances, and methods for preventing or improving the deterioration and loss of skin dermal tissue (promoting the production of extracellular matrix and suppressing the production of MMP (matrix metalloproteinase) For example, inhibition of its activity). Particularly in the cosmetics manufacturing industry, importance has been placed on oxidative protection and the prevention or improvement of alteration and loss of skin dermal tissue, which suppresses or eliminates the production of active oxygen and lipid peroxides that cause oxidation, such as thiotaurine. Anti-oxidants (Non-patent Documents 3, 4 and 5) and skin dermis tissue alteration and loss such as cucumber extract, cucumber extract, cedar extract, perilla extract, seaweed extract Purposes include collagen production promoters (Non-patent Documents 5 and 6) such as cuspid extract, L-ascorbic acid derivative, L-hydroxyproline, and camellia extract; MMP activity inhibitors (Non-patent Documents 7 and 8) and the like have been newly developed, and their application to cosmetics has been proposed. As described above, various antioxidants, MMP activity inhibitors, or skin dermal tissue production promoters such as collagen and elastin have been developed so far. For this purpose, various highly effective components are eagerly awaited, and new development has been continued even now.
FRAGRANCE JOURNAL, vol.26, No.12, 1998, 9-14 FRAGRANCE JOURNAL, vol.26, No.12, 1998, 33-38 FRAGRANCE JOURNAL, vol.28, No.12, 2000, 38-42 FRAGRANCE JOURNAL, vol.28, No.12, 2000, 22-27 FRAGRANCE JOURNAL, vol.30, No.6, 2002, 38-42 FRAGRANCE JOURNAL, vol.30, No.6, 2002, 119-123

  Therefore, the problem to be solved is the development of a novel active ingredient having a high whitening effect or skin aging prevention effect and its application to a cosmetic composition.

The present inventor has excellent melanin production inhibitory action, antioxidant action, collagen production promoting action, MMP (collagenase or elastase) production inhibitory action, skin elasticity improving effect, and anti-inflammatory action, which are excellent in squaric acid derivatives or salts thereof. And by using the squaric acid derivative or salt thereof, it was found that a cosmetic composition capable of exhibiting an excellent whitening effect and an anti-skin aging effect could be constructed, and the present invention was completed. It was. In addition, about the squaric acid derivative or its salt used by this invention, the squaric acid dibutyl ester has been used as a hair loss therapeutic agent conventionally (nonpatent literature 9). In addition, squaric acid derivatives have been tested as VLA-4 integrin antagonists (Non-patent Document 10). Furthermore, application to herbicidal and plant growth regulators (Patent Document 3) and nematicides (Patent Document 4) is disclosed. However, a technique in which the squaric acid derivative of the present invention or a salt thereof is applied to a cosmetic composition has not yet been disclosed and is a novel use.
West Japan Dermatology, vol.56, No.1, 1994, 105-108 Bioorganic & Medicinal Chemistry Letters, vol.12, No.7, 2002, 1051-1054 Japanese Patent Laid-Open No. 51-130530 Japanese Patent Publication No. WO00 / 24250

  That is, the present invention provides a cosmetic composition containing at least one selected from squaric acid derivatives or salts thereof (excluding squaric acid dibutyl ester).

  The product of the present invention has a remarkable melanin production inhibitory action, antioxidant action, collagen production promoting action, MMP (collagenase or elastase) production inhibitory action, and skin elasticity improvement effect possessed by a squaric acid derivative or a salt thereof. It constitutes a cosmetic composition having a whitening effect and an anti-skin aging effect. By applying the cosmetic composition of the present invention to the skin, skin darkening such as spots, buckwheat, sunburn, etc. is prevented or improved, and wrinkles and dullness, skin sagging, skin flexibility and elasticity are prevented from being reduced or reduced. It is possible to improve. Further, since the squaric acid derivative or a salt thereof in the present invention has an excellent anti-inflammatory action, it can be applied to cosmetics intended to improve rough skin, prevent atopy, or improve allergic dermatitis as an anti-inflammatory agent. Formulation is also included in the scope of inclusion of the present invention. Furthermore, since the squaric acid derivative or a salt thereof in the present invention has an excellent antioxidant action, it is also included in the scope of the present invention to be incorporated into cosmetics applied to hair or nails as an antioxidant.

  The squaric acid derivative used in the present invention is a compound represented by the following structural formula.

：（一般式１）

−Ｏ−Ｒ^３：（一般式２）

−Ｓ−Ｒ^３：（一般式３）

−ＰＯ_３−Ｒ^４：（一般式４）

−ＳＯ_３−Ｒ^４：（一般式５）

：（一般式６）

：（一般式７）

−ＣＯ−Ｒ^５：（一般式８）

−Ｏ−Ｒ^６：（一般式９）

［一般式１中のＲ^１及びＲ^２は互いに独立して、ヒドロキシル基、ハロゲン、低級アルコキシ基、ハロゲン化低級アルコキシ基、低級アルケニルオキシ基、ハロゲン化低級アルケニルオキシ基、カルボキシル基、低級アルコキシカルボニル基、置換されている低級アルコキシカルボニル基、メルカプト基、低級アルキルチオ基、脂肪族炭化水素基、置換されている脂肪族炭化水素基、芳香族炭化水素基またはヘテロ環式基（芳香族炭化水素基及びヘテロ環式基は、ハロゲン、ヒドロキシル基、カルボキシル基、アミノ基、低級アルキル基、低級アルケニル基、ハロゲン化低級アルキル基、ハロゲン化低級アルケニル基、低級アルコキシ基、低級アルケニルオキシ基、ハロゲン化低級アルコキシ基、ハロゲン化低級アルケニルオキシ基、メルカプト基及び低級アルキルチオ基からなる群から選択された１〜５の置換基を有していてもよい）で置換されている脂肪族炭化水素基、芳香族炭化水素基またはヘテロ環式基（芳香族炭化水素基及びヘテロ環式基は、ハロゲン、ヒドロキシル基、カルボキシル基、アミノ基、低級アルキル基、低級アルケニル基、ハロゲン化低級アルキル基、ハロゲン化低級アルケニル基、低級アルコキシ基、低級アルケニルオキシ基、ハロゲン化低級アルコキシ基、ハロゲン化低級アルケニルオキシ基、メルカプト基及び低級アルキルチオ基からなる群から選択された１〜５の置換基を有していてもよい）、あるいは一般式２または一般式３で示される基（一般式２及び３中のＲ^３は置換されていてもよい脂肪族炭化水素基、アミノ基、脂環式炭化水素基、芳香族炭化水素基、ヘテロ環式基、糖残基、リン酸基または一般式４で示される置換されたリン酸基（一般式４中のＲ^４はＣ１〜Ｃ６のアルキル基またはアミノアルキル基）、硫酸基または一般式５で示される置換された硫酸基（一般式５中のＲ^４はＣ１〜Ｃ６のアルキル基またはアミノアルキル基）、一般式６で示されるトコフェロール付加物、一般式７で示されるトコトリエノール付加物、または一般式８で示される基（一般式８中のＲ^５は、置換されていてもよい脂肪族炭化水素基もしくは芳香族炭化水素基、または一般式９で示される基（一般式９中のＲ^６は水素原子または置換されていてもよい脂肪族炭化水素基）））を示す。但し、Ｒ ^１ 及びＲ ^２ が共にヒドロキシル基とはならない。］

: (General formula 1)

^-O-R 3 :( Formula 2)

^-S-R 3 :( Formula 3)

-PO ₃ -R ⁴ :( general formula 4)

-SO ₃ -R ⁴ :( Formula 5)

: (General formula 6)

: (General formula 7)

^-CO-R 5 :( Formula 8)

^-O-R 6 :( Formula 9)

[R ¹ and R ^{2 in} General Formula 1 are independently of each other a hydroxyl group, a halogen, a lower alkoxy group, a halogenated lower alkoxy group, a lower alkenyloxy group, a halogenated lower alkenyloxy group, a carboxyl group, or a lower alkoxycarbonyl. Group, substituted lower alkoxycarbonyl group, mercapto group, lower alkylthio group, aliphatic hydrocarbon group, substituted aliphatic hydrocarbon group, aromatic hydrocarbon group or heterocyclic group (aromatic hydrocarbon group) And a heterocyclic group includes halogen, hydroxyl group, carboxyl group, amino group, lower alkyl group, lower alkenyl group, halogenated lower alkyl group, halogenated lower alkenyl group, lower alkoxy group, lower alkenyloxy group, halogenated lower group Alkoxy group, halogenated lower alkenyloxy group, mel An aliphatic hydrocarbon group, an aromatic hydrocarbon group, or a heterocyclic group (aromatic group) substituted with 1 to 5 substituents selected from the group consisting of a putto group and a lower alkylthio group Group hydrocarbon group and heterocyclic group are halogen, hydroxyl group, carboxyl group, amino group, lower alkyl group, lower alkenyl group, halogenated lower alkyl group, halogenated lower alkenyl group, lower alkoxy group, lower alkenyloxy group 1 to 5 substituents selected from the group consisting of a halogenated lower alkoxy group, a halogenated lower alkenyloxy group, a mercapto group and a lower alkylthio group), or a general formula 2 or a general formula 3 a group represented by (formula 2 and 3 in R ³ is optionally substituted aliphatic hydrocarbon group, an amino group, an alicyclic hydrocarbon group, Aromatic hydrocarbon group, heterocyclic group, sugar residues, phosphate groups or the general formula R ⁴ in a substituted phosphoric acid group (formula 4 shown by 4 is an alkyl group or an aminoalkyl group C1~C6 ), substituted sulfate group represented by the sulfate group or the general formula 5 (R ⁴ of the general formula 5 in C1~C6 alkyl or aminoalkyl group), tocopherol adducts represented by general formula 6, formula 7 Or a group represented by general formula 8 (R ^{5 in} general formula 8 is an optionally substituted aliphatic hydrocarbon group or aromatic hydrocarbon group, or represented by general formula 9) Group (R ^{6 in} general formula 9 is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group)). However, R ¹ and R ² are not both hydroxyl groups. ]

“Lower” in the structural formula represents a group having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms, particularly preferably 1 to 4 carbon atoms. The “aliphatic aliphatic hydrocarbon group” in R ¹ , R ² , R ³ , R ⁵ and R ⁶ in the above structural formula is a linear or branched fatty acid of an alkyl group, an alkenyl group and an alkynyl group. Represents a hydrocarbon group.

  The alkyl group of the aliphatic hydrocarbon group is a linear or branched alkyl group having 1 to 30 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl, t -Butyl, pentyl, isopentyl, neopentyl, t-pentyl, 1-ethylpropyl, hexyl, isohexyl, heptyl, octyl, nonyl, decyl, tetrahydrogeranyl, undecyl, dodecyl (lauryl), tridecyl, tetradecyl (myristyl), pentadecyl, hexadecyl (Palmityl, triisopalmityl), heptadecyl, octadecyl (stearyl), nonadecyl, icosanyl (eicosanyl), heicosanyl, docosanyl, tricosanyl, tetracosanyl, pentacosanyl, hexacosanyl, heptacosanyl, octacosanyl, no Examples include nacosanil and triacontanil.

  The alkenyl group of the aliphatic hydrocarbon group is a linear or branched alkenyl group having 2 to 28 carbon atoms having at least one double bond, such as vinyl, allyl, propenyl, isopropenyl, methylpropenyl. , Butenyl, methylbutenyl, ethylbutenyl, pentenyl, methylpentenyl, ethylpentenyl, hexenyl, methylhexenyl, heptenyl, heptadienyl, octenyl, octadienyl, nonenyl, nonadienyl, decenyl, decadienyl, undecenyl, decenyl, decenyl, decenyl , Pentadecenyl, pentadecadienyl, hexadecenyl (palmitoleil), hexadecadienyl, heptadecenyl, heptadecadienyl, octadecenyl (oleyl) , Octadecadienyl, nonadecenyl, nonadecadienyl, icocenyl (eicosenyl), henycocenyl, dococenyl, docosadienyl, tricocenyl, tricosadienyl, tetracosenyl, tetracosadienyl, pentacocenyl, pentacosadienyl, hexacocenyl, hexacocacenyl, Examples include sadienyl, octacosenyl, octacosadienyl, and tetramethylhexadecenyl.

  The alkynyl group of the aliphatic hydrocarbon group is a linear or branched alkynyl group having 2 to 28 carbon atoms having at least one triple bond, such as ethynyl, propynyl, methylpropynyl, butynyl, methylbutynyl, pentynyl. , Methylpentynyl, hexynyl, heptynyl, octynyl, decynyl, tridecynyl, tetradecynyl, pentadecynyl, hexadecynyl, heptadecynyl, octadecynyl, nonadecynyl, eicosinyl, heneicosinyl, docosinyl, tricosinyl, tetracosinyl, pentacosinyl, hexacosinyl, hexacosinyl, hexacosinyl, hexacosinyl, hexacosinyl, hexacosinyl, hexacosinyl

The substituents of “substituted aliphatic hydrocarbon” in R ¹ and R ² in the above structural formula are each independently halogen, hydroxyl group, lower alkoxy group, halogenated lower alkoxy group, lower alkenyloxy group, Halogenated lower alkenyloxy group, carboxy group, phenyloxy group, lower alkoxycarbonyl group, halogenated lower alkoxycarbonyl group, lower alkenyloxycarbonyl group, halogenated lower alkenyloxycarbonyl group, lower alkynyloxycarbonyl group, phenyloxycarbonyl group , Lower alkanoyloxy group, carbamoyl group, cyano group, sulfonyl group, sulfonic acid group, phosphoric acid group, silyl group, mercapto group, lower alkylthio group, amino group, mono-lower alkylamino group, di-lower alkylamino group, aromatic Carbonization Prime group and heterocyclic group (aromatic hydrocarbon group and heterocyclic group are halogen, hydroxyl group, carboxyl group, amino group, lower alkyl group, lower alkenyl group, halogenated lower alkyl group, halogenated lower alkenyl group , A lower alkoxy group, a lower alkenyloxy group, a halogenated lower alkoxy group, a halogenated lower alkenyloxy group, a mercapto group, and a lower alkylthio group. The number of these substituents is not particularly limited, but is preferably 1 to 5, particularly preferably 1 to 3. The substituents may be the same or different from each other, and the position of the substituent on the molecule is not particularly limited.

  “Halogen” in the above structural formula includes fluorine, chlorine, bromine and iodine.

The substituents of “optionally substituted aliphatic hydrocarbon” in R ³ , R ⁵ and R ⁶ in the structural formula are each independently halogen, hydroxyl group, lower alkoxy group, halogenated lower alkoxy group, Lower alkenyloxy group, halogenated lower alkenyloxy group, carboxy group, phenyloxy group, lower alkoxycarbonyl group, halogenated lower alkoxycarbonyl group, lower alkenyloxycarbonyl group, halogenated lower alkenyloxycarbonyl group, lower alkynyloxycarbonyl group , Phenyloxycarbonyl group, lower alkanoyloxy group, carbamoyl group, cyano group, sulfonyl group, sulfonic acid group, phosphoric acid group, silyl group, mercapto group, lower alkylthio group, amino group, mono-lower alkylamino group, di-lower alkyl amino Group, aromatic hydrocarbon group and heterocyclic group (aromatic hydrocarbon group and heterocyclic group are halogen, hydroxyl group, carboxyl group, amino group, lower alkyl group, lower alkenyl group, halogenated lower alkyl group, 1 to 5 substituents selected from the group consisting of a halogenated lower alkenyl group, a lower alkoxy group, a lower alkenyloxy group, a halogenated lower alkoxy group, a halogenated lower alkenyloxy group, a mercapto group, and a lower alkylthio group And the number of these substituents is not particularly limited, but is preferably 1 to 5, particularly preferably 1 to 3. The substituents may be the same or different from each other, and the position of the substituent on the molecule is not particularly limited.

When the substituent of “optionally substituted aliphatic hydrocarbon” in R ³ , R ⁵ and R ⁶ in the structural formula is at least one amino group, the amino group is bonded with an amide bond. Such amino acid adducts are also encompassed within the scope of the substituents. Examples of amino acids to be added include valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, aspartic acid, glutamic acid, hydroxylysine, Arginine, ornithine, histidine, carnitine and the like can be mentioned, which may be added to a part of the amino group which is a substituent or all amino groups.

The substituents of the “substituted lower alkoxycarbonyl group” in R ¹ and R ² in the above structural formula are each independently halogen, hydroxyl group, lower alkoxy group, halogenated lower alkoxy group, lower alkenyloxy group, Halogenated lower alkenyloxy group, carboalkyl group, lower alkoxycarbonyl group, mercapto group, lower alkylthio group, aromatic hydrocarbon group and heterocyclic group (aromatic hydrocarbon group and heterocyclic group are halogen, hydroxyl group, Carboxyl group, amino group, lower alkyl group, lower alkenyl group, halogenated lower alkyl group, halogenated lower alkenyl group, lower alkoxy group, lower alkenyloxy group, halogenated lower alkoxy group, halogenated lower alkenyloxy group, mercapto group And a lower alkylthio group At least one selected from the group (which may have 1 to 5 substituents selected from the group), and the number of these substituents is not particularly limited, but is preferably 1 to 5, particularly preferably Is 1 to 3. The substituents may be the same or different from each other, and the position of the substituent on the molecule is not particularly limited.

  The lower alkoxy group in the structural formula is not particularly limited as long as it belongs to the definition of “lower”. For example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, neobutoxy, t-butoxy, pentoxy, isopentoxy, etc. Is mentioned.

  The “halogenated” in the structural formula indicates a compound substituted with at least one or more of the “halogen”.

  The “lower alkenyloxy group” in the structural formula is not particularly limited within the range belonging to the definition of “lower”, and examples thereof include vinyloxy, allyloxy, propenyloxy, methylpropenyloxy, butenyloxy, ethylbutenyloxy and the like. It is done.

  The “lower alkylthio group” in the structural formula is not particularly limited within the range belonging to the definition of “lower”, and examples thereof include methylthio, ethylthio, propylthio, isopropylthio, n-butylthio and t-butylthio.

  The “lower alkoxycarbonyl group” in the structural formula is not particularly limited within the range belonging to the definition of “lower”, but for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, and t -Butoxycarbonyl and the like.

The “lower alkyl group” in R ¹ , R ² , R ³ , R ⁵ and R ⁶ in the structural formula is not particularly limited within the range belonging to the definition of “lower”, but for example, methyl, ethyl, propyl, Examples include isopropyl, n-butyl, isobutyl, s-butyl, and t-butyl.

The “lower alkenyl group” in R ¹ , R ² , R ³ , R ⁵ and R ⁶ in the structural formula is not particularly limited within the range belonging to the definition of “lower”, but for example, vinyl, allyl, isopropenyl , Propenyl, methylpropenyl, butenyl, ethylbutenyl, methylbutenyl and the like.

The “lower alkenyloxycarbonyl group” in R ¹ , R ² , R ³ , R ⁵ and R ⁶ in the structural formula is not particularly limited within the range belonging to the definition of “lower”, for example, vinyloxycarbonyl, Examples include allyloxycarbonyl, isopropenyloxycarbonyl, propenyloxycarbonyl, butenyloxycarbonyl and the like.

The “lower alkynyloxycarbonyl group” in R ¹ , R ² , R ³ , R ⁵ and R ⁶ in the structural formula is not particularly limited within the range belonging to the definition of “lower”, but for example, ethynyloxycarbonyl, Examples include propynyloxycarbonyl, butynyloxycarbonyl, and 2-penten-4-ynyloxycarbonyl.

The “lower alkanoyloxy group” in R ¹ , R ² , R ³ , R ⁵ and R ⁶ in the structural formula is not particularly limited within the range belonging to the definition of “lower”, but for example, acetyloxy, ethylcarbonyl Oxy, propylcarbonyloxy, isopropylcarbonyloxy, n-butylcarbonyloxy, isobutylcarbonyloxy, t-butylcarbonyloxy, n-pentylcarbonyloxy, isopentylcarbonyloxy, neopentylcarbonyloxy, t-pentylcarbonyloxy, and hexyl And carbonyloxy.

Examples of the “carbamoyl group” for R ¹ , R ² , R ³ , R ⁵ and R ⁶ in the above structural formula include, in addition to unsubstituted carbamoyl, N-mono-lower alkylcarbamoyl, N, N-di-lower. Alkylcarbamoyl, N-hydroxycarbamoyl, N-lower alkoxycarbamoyl, N-hydroxy-N-lower alkylcarbamoyl, N-lower alkoxy-N-lower alkylcarbamoyl, N-phenylcarbamoyl, N-phenyl-N-lower alkylcarbamoyl, And substituted carbamoyl such as N-substituted phenylcarbamoyl.

Examples of the “sulfonyl group” in R ¹ , R ² , R ³ , R ⁵ and R ⁶ in the above structural formula include, in addition to unsubstituted sulfonyl, alkylsulfonyl such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, etc. Examples include substituted sulfonyls such as phenylsulfonyl and hydroxyethylsulfonyl.

Examples of the “silyl group” in R ¹ , R ² , R ³ , R ⁵ and R ⁶ in the above structural formula include, in addition to unsubstituted silyl, lower alkylsilyl such as methylsilyl, dimethylsilyl, trimethylsilyl, or halogen. Substituted silyls such as modified lower alkylsilyls.

Examples of the "mono-lower alkylamino group" in ^{R 1, R 2, R 3} , R 5 and R ⁶ in the structural formula above is not particularly limited in the range belonging to the definition of "lower", for example methylamino, ethyl Amino, propylamino, isopropylamino, butylamino, pentylamino and the like can be mentioned.

The “phosphate group” in R ³ , R ⁵ and R ⁶ in the structural formula is an unsubstituted phosphate group or pyrophosphate group, and further a substituent in “optionally substituted aliphatic hydrocarbon”. And a substituted phosphoric acid group or a substituted pyrophosphoric acid group substituted with the same substituent.

  The “aromatic hydrocarbon group” in the structural formula is not particularly limited, and examples thereof include phenyl, benzyl, indenyl, naphthyl, anthryl, phenanthryl, acenaphthylenyl, fluorenyl and the like.

  The “heterocyclic group” in the structural formula is not particularly limited as long as it is a monocyclic or polycyclic heterocyclic group, and is selected from a nitrogen atom, an oxygen atom, a sulfur atom, and a selenium atom. Examples thereof include 5- to 10-membered monocyclic or polycyclic heterocyclic groups having a hetero atom as a ring-constituting atom, and a complex including a transition element such as a copper atom, an iron atom, or a zinc atom. Included. Specifically, monocyclic heterocyclic groups include isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, 1,2,3-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl, thiazolyl, 1,2,3-thiadiazolyl, 1 , 2,4-thiadiazolyl, 1,3,4-thiadiazolyl, thienyl, tetrazolyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, pyranyl, pyrazinyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrrolyl , Furazanyl, and furyl. Specifically, examples of the polycyclic heterocyclic group include acridinyl, 5-azabenzo [a] anthracenyl, isoindolyl, isoquinolyl, isochromanyl, isobenzofuranyl, imidazo [2,1-b] thiazolyl, 4H-imidazo [4 , 5-d] thiazolyl, imidazo [1,2-b] [1,2,4] triazinyl, imidazo [1,2-a] pyridyl, imidazo [1,5-a] pyridyl, imidazo [1,2- b) pyridazinyl, imidazol [1,2-a] pyrimidinyl, imidazolidinyl, imidazolinyl, 1H-indazolyl, indolidinyl, indolyl, 4H [1,3] -oxathiolo [5,4-b] pyrrolyl, 1H-2-oxapyrenyl, carbazolyl , Α-Carborinyl, β-Carborinyl, γ-Carborinyl, Quinazolinyl, Quinoxalinyl, Quinolyl, Chromanyl, 4H-1,3-Dioxolo [4,5-b] imidazolyl, Cyclopenta [b] pyranyl, 2 , 3-dithia-1,5-diazaindanyl, 4H-1,3-dithiaphthalenyl, 1,4-dithiaphthalenyl, cinnonyl, thianthenyl, thieno [2,3-b] furanyl, 2,7,9 -Triazaphenanthrenyl, 1,2,4-triazolo [4,3-a] pyridazinyl, 1,2,4-triazolo [4,3-a] pyridyl, 2,4,6-trithia-3a, 7a-diazaindanyl-naphthyridinyl, piperazinyl, piperidyl, pyrazolidinyl, 7H-pyrazino [2,3-c] carbazolyl, pyrazino [2,3-d] pyridazinyl, 1H-pyrazolo [4,3-d] oxazolyl, pyrazolo [1, 5-a] pyridyl, pyrido [1 ', 2': 1,2] imidazo [4,5-b] quinoxalinyl, 5H-pyrido [2,3-d] -o-oxazinyl, 4H-pyrido [2,3 -c] carbazolyl, pyrrolidinyl, pyrrolinyl, 1H-pyrrolo [1,2-b] [2] benzoazepinyl, pyrrolo [1,2-b] pyridazinyl, phenazinyl, phenatridinyl, Enatrolinyl, phenoxazinyl, phenoxathinyl, phenothiazinyl, phthalazinyl, buteridinyl, brinyl, 2H-furo [3,2-b] pyranyl, furo [3,4-c] cincinolinyl, 1,2-benzisoxazolyl, Benzo [h] isoquinolyl, 1,2-benzisothiazolyl, benzimidazolyl, benzoxazolyl, 4H-3,1-benzoxazinyl, 3-benzoxepinyl, benzothiazolyl, benzo [b] thienyl, 1H- Benzotriazolyl, benzo [b] furanyl, morpholinyl, 2-methylene-2,3-dihydro-1H-indole, 2-methylene-2,3-dihydrobenzothiazole, 2-methylene-2,3-dihydrobenzoselena Sol, 5-methylene-4,5-dihydro- [1,2,4] -thiadiazole, 2-methylene-2,3-dihydrothiazole, 4-methylene-4H-chromene, 4-methylene-4H-thiopyran, 2 -Methylene- 1,2-dihydroquinoline and the like can be mentioned.

The “phosphate group” in R ³ , R ⁵ and R ⁶ in the structural formula is the same substituent as the substituent in “Substituted aliphatic hydrocarbon” in addition to phosphoric acid or pyrophosphoric acid. Examples thereof include substituted phosphoric acid or substituted pyrophosphoric acid.

As the “sulfonic acid group” in R ³ , R ⁵ and R ⁶ in the structural formula, in addition to the sulfonic acid, a substituent similar to the substituent in the “substituted aliphatic hydrocarbon” is further substituted. And substituted sulfonic acid.

The “sugar residue” for R ³ in the structural formula can be selected from monosaccharides, disaccharides, oligosaccharides, and the like, and is not particularly limited. Examples include rhamnoside, deoxymannosyl glucoside, deoxygalactosyl glucoside.

The “alicyclic hydrocarbon group” for R ³ in the structural formula is a saturated or unsaturated monocyclic or polycyclic alicyclic hydrocarbon group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclo Cycloalkyl groups such as heptyl, cyclooctyl, bicycloheptyl, bicyclooctyl, bicyclononyl, bicyclodecyl, adamantine, 2-cyclopentyl-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3- Cycloalkenyl groups such as cyclohexen-1-yl and cycloalkadienyls such as 2,4-cyclopentadien-1-yl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl And a substituted alicyclic hydrocarbon group substituted with the same substituent as the substituent in the “substituted aliphatic hydrocarbon”. It is.

The “alkyl group” for R ⁴ in the structural formula is not particularly limited as long as it is in the range of 1 to 6 carbon atoms. For example, methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, pentyl, isobutyl Hexyl and the like.

The “aminoalkyl group” for R ⁴ in the structural formula is not particularly limited as long as it has 1 to 6 carbon atoms. For example, aminomethyl, aminoethyl, aminopropyl, aminoisopropyl, aminobutyl, aminopentyl, Examples include aminoisobutyl and aminohexyl.

The amino group of "aminoalkyl group" for R ⁴ in the structural formula, amino acid addition product obtained by the amino group and the amide bond are also encased within the squaric acid derivatives used in the present invention. Examples of amino acids to be added include valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, aspartic acid, glutamic acid, hydroxylysine, Arginine, ornithine, histidine, carnitine, etc. are mentioned, It may be added to a part of amino group which an aminoalkyl group has, or may be added to all amino groups.

  The “tocopherol adduct” represented by the general formula 6 is a residue when the 6-position of the tocopherol is bonded to the oxygen atom represented by the general formula 2 or the sulfur atom represented by the general formula 3. As the tocopherol, any of isomers of α-form, β-form, γ-form and delta-form can be used.

  The “tocotrienol adduct” represented by the general formula 7 is a residue when the 6-position of the tocotrienol is bonded to the oxygen atom represented by the general formula 2 or the sulfur atom represented by the general formula 3. As the tocotrienol, any of the isomers α, β, γ, and δ can be used.

  The salt of the squaric acid derivative used in the present invention is preferably a pharmacologically acceptable salt, a salt with an inorganic base, a salt with an organic base, a salt with an inorganic acid, a salt with an organic acid, and a base And salts with acidic or acidic amino acids. Specific examples of the salt with an inorganic base include sodium salt, potassium salt, calcium salt, magnesium salt, barium salt, lithium salt, and aluminum salt. Examples of the salt with an organic base include ammonium salt, trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, diethanolamine salt, triethanolamine salt, dichloroamineamine salt, and dibenzylethylenediamine salt. Examples of the salt with inorganic acid include hydrochloride, hydrofluoride, hydrobromide, nitrate, sulfate, phosphate, perchlorate, hydroiodide, and the like. As salts with organic acids, formate, acetate, trifluoroacetate, fumarate, oxalate, tartrate, maleate, citrate, succinate, malate, mandelate, Examples include ascorbate, lactate, gluconate, metasulfonate, toluenephosphonate, and benzenesulfonate. Examples of salts with basic or acidic amino acids include arginine, lysine, ornithine, aspartic acid, glutamic acid and the like.

  As the squaric acid derivative or salt thereof used in the present invention, pharmacologically acceptable hydrates and hydrated salts can also be used. Specific examples include monohydrate, dihydrate, trihydrate and hexahydrate, and these hydrates or hydrate salts can be prepared according to a conventional method.

  The squaric acid derivative or salt thereof used in the present invention is preferably one or more selected from the compound group represented by the general formula 1 and general formula 2, and particularly preferably the general formula 1 and general salt. A squaric acid glycoside represented by a sugar residue in Formula 2, an alkali metal salt or an alkaline earth metal salt of squalyl phosphate represented by a phosphate group in General Formula 1 and General Formula 2, and General Formula 1, General The phosphoric acid squaryl ester represented by the formula 2 and the general formula 4, the alkali metal salt or the alkaline earth metal salt of the squaryl sulfate represented by the sulfate group in the general formula 1 and the general formula 2, the general formula 1 and the general formula 2 And the sulfuric acid squarylate ester represented by the general formula 5, the tocopherol-added squaric acid represented by the general formula 1, the general formula 2 and the general formula 6, the general formula 1, the general formula And squaric acid esters represented by the general formula 8 can be mentioned.

  As a method for synthesizing a squaric acid derivative or a salt thereof used in the present invention, it is produced and prepared by a known method. Specifically, JP-A No. 51-130530, J. Am. Chem. Soc., 96 (1974), J. Am. Chem. Soc., 88, 1533 (1966), J. Am. Chem. Soc. ., 96,3006 (1974), J. Am.Chem.Soc., 81,2678 (1959), J. Am.Chem.Soc., 119,12125-12130 (1997), Angew.Chem., 78,927 ( 1966), Angew.Chem., 75,982 (1963), Angew.Chem., 81,917 (1969), Angew.Chem., 84,480 (1972), Angew.Chem., 84,5481 (1972), Angew.Chem., 87,491 (1975), Angew.Chem., 86,574 (1974), Beri.Dtsch.Chem.Ges., 103,3553 (1970), Beri.Dtsch.Chem.Ges., 104,873 (1971), Science, 179,1324 (1973), Gazz.chim.ital., 102,818 (1972), Ann.Chem., 686,55 (1965), Ann.Chem., 742,116 (1970), Tetrahedron Letters., 38,40,7091-7094 ( 1997), J. Org. Chem., 25, 1008 (1963), J. Org. Chem., 32, 3703 (1967), J. Org. Chem., 60, 1470-1472 (1995), Chemistyr Letters, 927 (1972), Bull. Soc. Chim. France., 1974, 529, Biosci., 46, 498-501 (1991), Synth. Commun., 27.2177-2180 (1997), Synthesis, 961-993 (1980), etc. The method described is mentioned. In particular, in the case where the derivative is an ester former (including phosphate ester and sulfate ester), it is produced and prepared by a simple method such as a compound having a simple carbonyl group in organic synthesis and a dehydration reaction by adding a catalyst and heating. can do. Further, squaric acid, which is widely used as a raw material for producing derivatives, is also produced and prepared by a known method, and specifically, the method described in Journal of Synthetic Organic Chemistry, Vol. 53, No. 4 (1995), (1 ) [2 + 2] cycloaddition reaction, (2) synthesis method using moniliformin as raw material, (3) synthesis method using butadiene derivative as raw material, (4) synthesis method by electrochemical reduction of carbon monoxide, ( 5) Synthesis method using triketene as a raw material.

  The dosage form of the cosmetic composition in the present invention is arbitrary, ampoules, capsules, powders, granules, pills, tablets, solids, liquids, gels, bubbles, emulsions, creams, Ointments, sheets, mousses, powder dispersions, multilayers, aerosols and other dosage forms can be constructed. Specifically, skin lotion, essence, whitening lotion, milk, whitening milk, cream, whitening cream, ointment, whitening ointment, lotion, whitening lotion, oil, pack and other basic cosmetics, soap, cleansing cream, cleansing Skin cleanser such as lotion, cleansing milk, face wash, shampoo, rinse, hair care cosmetics such as hair treatment, hair cream, hair spray, hair tonic, hair gel, hair lotion, hair oil, hair essence, hair water, hair wax Hair conditioner such as hair foam, hair growth / hair nourishing agent, one-component hair dye or two-component hair dye, hair color etc., permanent wave agent or hair straightener, permanent agent or wave retaining agent Hair cosmetics such as foundation, white powder, funny, lipstick, blusher, eye shadow, eyeliner , Makeup cosmetics such as mascara, eyebrows and eyelashes, cosmetics for finishing such as nail care, perfumes, bath preparations, other toothpastes, mouth fresheners, mouthwashes, gums, candy, tablets, etc. Examples include compositions, liquid odor / deodorant, hygiene products, sanitary cotton, and wet tissue.

  The amount of the squaric acid derivative or salt thereof to be added to the cosmetic composition in the present invention is slightly different depending on the type of cosmetic composition, the quality, and the degree of expected action, and is not particularly limited. Among them, it is generally used in a concentration range of 0.0001% by mass or more, preferably 0.01 to 50.0% by mass, particularly preferably 0.1 to 20% by mass.

  The cosmetic composition of the present invention includes, in addition to the essential component squaric acid derivative or a salt thereof, further pigmentation inhibitors exemplified below, tyrosinase activity inhibitors, melanocyte melanin production inhibitors, melanin production promoters, moisturizing agents. Agents, cell activators / metabolic activators, antioxidants, active oxygen scavengers / radical formation inhibitors, fat metabolism promoters, UV protection agents / UV absorption promoters, astringents, anti-inflammatory agents / interleukin production suppression Agent / anti-inflammatory agent, antiseborrheic agent, antibacterial agent / antiviral agent, blood flow promoter / vascular stimulant, antiandrogen agent, structural proteolytic enzyme (elastase, collagenase, keratin protease, serine protease, integrin degrading enzyme, involucrin Degrading enzyme, filaggrin degrading enzyme, laminin degrading enzyme, fibronectin degrading enzyme, proteoglycan Enzymes, etc.) Activity inhibitors, structural protein synthesis promoters, mucopolysaccharide (hyaluronic acid, chondroitin sulfate, etc.) degrading enzyme inhibitors, mucopolysaccharide synthesis promoters, intercellular adipogenesis promoters / intercellular lipid state improvers, Keratolytic agent / stratum corneum peeling promoter, plasminogen activator antagonist inhibitor, Maillard reaction inhibitor, testosterone 5α reductase activity inhibitor / hair papilla activator / hair growth promoter, hair matrix growth inhibitor / development Active ingredients such as hair suppressants, hair swelling agents / hair protectants, odorant elimination agents, and other plant-based materials, animal-based materials, and microbial-based materials that are preferred for use in forming cosmetic composition forms Excellent cosmetics with more functionality by selecting and using ingredients, extracts, metabolites, and other components derived from raw materials, other natural products, etc., or various compounds as additives. A composition can be provided. The content in the preparation is not particularly specified, but a concentration range of 0.0001 to 50% by weight is generally used.

(1) Pigmentation inhibitor Specifically, p-aminobenzoic acid derivatives, salicylic acid derivatives, benzenesulfonamide derivatives, imidazole derivatives, naphthalene derivatives, hydroxyanthranilic acid or salts thereof and derivatives thereof, anthranilic acid derivatives, coumarins Derivatives, amino acid derivatives (2-amino-3- [1-carboxyl-2- (1H-imidazol-4-yl) ethyl] aminobutanoic acid, 2-amino-3- [1-carboxyl-2- (1H- Imidazol-4-yl) ethyl] aminobutanoic acid hydrochloride, 2-amino-3- [1-carboxyl-2- (1H-imidazol-4-yl) ethyl] aminobutanoic acid sodium salt, 2-amino- 3- [1-carboxyl-2- (1H-imidazol-4-yl) ethyl] aminobutanoic acid potassium salt, etc.), benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, geo Xanthane derivatives, camphor derivatives, furan derivatives, pyrone derivatives, nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, ascorbic acid or salts thereof and derivatives thereof (phosphate-L-ascorbic acid magnesium, ascorbyl palmitate, ascorbyl dipalmitate, Ascorbic acid hydroxyproline phosphate, 5-o-α-D-glucopyranosyl-L-ascorbic acid, L-ascorbic acid phosphate sodium salt, L-ascorbic acid phosphate potassium salt, L-ascorbic acid phosphate Magnesium salt, L-ascorbic acid phosphate calcium salt, L-ascorbic acid phosphate aluminum salt, L-ascorbic acid sulfate sodium salt, L-ascorbic acid sulfate potassium salt, L-ascorbic acid sulfate mag Cium salt, L-ascorbic acid sulfate calcium salt, L-ascorbic acid sulfate aluminum salt, L-ascorbic acid sodium salt, L-ascorbic acid potassium salt, L-ascorbic acid magnesium salt, L-ascorbic acid calcium salt, L -Aluminum ascorbate, 6-o-α-D-galactopyranosyl-L-ascorbic acid, 2-o-β-D-galactopyranosyl-L-ascorbic acid, magnesium L-ascorbate phosphate Salt, L-ascorbic acid phosphate sodium salt, L-ascorbic acid sulfate sodium salt, 6-o-acyl ascorbic acid phosphate sodium salt, 6-o-acyl ascorbic acid phosphate ammonium salt, 6-o -Acyl ascorbic acid phosphate isopropanolamine salt, 3-o-isopropyl-L-ascorbic acid, 6-o-alkyl Ascorbic acid phosphate potassium salt, 6-o-alkyl ascorbic acid phosphate calcium salt, 6-o-alkyl ascorbic acid phosphate barium salt, 6-o-alkyl ascorbic acid phosphate ammonium salt, 6-o -Alkylascorbic acid phosphate monoethanolamine salt, 6-o-alkylascorbic acid phosphate diethanolamine salt, 6-o-alkylascorbic acid phosphate triethanolamine salt, 6-o-alkylascorbic acid phosphate ester Monoisopropanolamine salt, 6-o-alkylascorbic acid phosphate diisopropanolamine salt, 6-o-alkylascorbic acid phosphate triisopropanolamine salt, 3-o-glycosyl-L-ascorbic acid, 6-o- β-D-galactopyranosyl-L-ascorbic acid, as Rubinic acid phosphate cholesterol ester, palmitic acid-L-ascorbyl, isopalmitic acid-L-ascorbyl, dipalmitic acid-L-ascorbyl, diisopalmitic acid-L-ascorbyl, stearic acid-L-ascorbyl, isostearic acid-L -Ascorbyl, distearic acid-L-ascorbyl, diisostearic acid-L-ascorbyl, myristic acid-L-ascorbyl, isomyristic acid-L-ascorbyl, dimyristic acid-L-ascorbyl, diisomyristic acid-L-ascorbyl, 2 -Ethylhexanoic acid-L-ascorbyl, di-2-ethylhexanoic acid-L-ascorbyl, oleic acid-L-ascorbic acid, 2-o-α-D-glucosyl-L-ascorbic acid, 2-o-α- D-maltosyl-L-ascorbic acid, 2-o-α-D-maltotriosyl-L-ascorbic acid, 3-o-α-D-glucosyl-L-ascorbic acid, 2-o-α-D-maltosyl - L-ascorbic acid, 2-o-α-D-maltotriosyl-L-ascorbic acid, L-ascorbic acid tetraisopalmitate, L-ascorbic acid tetralaurate, L-2-ascorbic acid tetra-2-ethyl Hexanoic acid ester, L-ascorbic acid tetraoleic acid ester, 5,6-isopropylidene-L-ascorbic acid, L-ascorbic acid retinol ester, L-ascorbic acid-DL-tocopherol phosphate ester, L-3-o- Ethyl ascorbic acid, L-ascorbic acid tristearate, L-ascorbic acid tripalmitate, L-ascorbic acid trioleate, L-ascorbic acid triphosphate, 2-o-ascorbyl cinnamate, 2-o-ascorbyl ferrate , 2-o-ascorbyl caffeate, 2-o-ascorbyl synapate, 2-o- [6-palmitoyl ascorbyl] -4'-ace Xifellate, DL-α-tocopherol-2-L-ascorbic acid diester, ascorbic acid inositol-conjugated derivative, ascorbic acid phosphoramide derivative, ascorbic acid arbutin conjugate, ascorbyl phosphoryl cholesterol, chromanyl ascorbic acid derivative, ascorbic acid sialic Acid derivatives, etc.), tocopherols or salts thereof and derivatives thereof (α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, ε-tocopherol, α-tocopheryl retinoate, aminomethylated tocopherol, hydroxymethylated tocopherol, Tocopheryl phosphate, tocopherol acetate, tocopherol nicotinate, tocopherol succinate, tocopherol linoleate, tocopherol orotate, DL-α-tocopheryl glucoside, DL-α-tocopheryl maltoside, DL-β-tocopheryl glucoside, DL-β-tocopheryl maltoside, DL-γ-tocopheryl glucoside, DL-γ-tocopheryl maltoside DL-δ-tocopheryl glucoside, DL-δ-tocopheryl maltoside, D-α-tocopheryl glucoside, D-α-tocopheryl maltoside, D-β-tocopheryl glucoside, D-β-tocopheryl maltoside Sid, D-γ-tocopheryl glucoside, D-γ-tocopheryl maltoside, D-δ-tocopheryl glucoside, D-δ-tocopheryl maltoside, L-α-tocopheryl glucoside, L-α-tocopheryl Maltoside, L-β-tocopheryl glucoside, L-β-tocopheryl maltoside, L-γ-tocopheryl glucoside, L-γ-tocopheryl maltoside, L-δ-tocopheryl glucoside, L-δ-toco Ferryl maltoside, 1- Rufoethylamino) -3- (α-tocopheryl-6-iroxy) propan-2-ol, 1- (carboxypropylamino) -3- (α-tocopheryl-6-iroxy) propan-2-ol Hydrochloride, S- [3- (α-tocopheryl-6-yloxy) -2-hydroxypropyl] cysteine, S- [3- (α-tocopheryl-6-iroxy) -2-hydroxypropyl]- γ-glutamylcystenylglycine, N- [3- (α-tocopheryl-6-iroxy) -2-hydroxypropyl] aspartic acid, N- [3- (α-tocopheryl-6-iroxy) -2 -Hydroxypropyl] glutamic acid, etc.), tocotrienol or a salt thereof and derivatives thereof (α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, tocotrienol acetate, tocotrienol nicotinate, tocotrienol Russuccinate, tocotrienol linoleate, tocotrienol orotate, etc.), kojic acid or derivatives thereof (2-methoxymethyl-hydroxy-4H-pyran-4-one, 2-ethoxymethyl-5-hydroxy-4H-pyran-4-one, 2-Benzolyloxymethyl-5-hydroxy-4H-pyran-4-one, 2-cinnamoyloxymethyl-5-hydroxy-4H-pyran-4-one, 2-phenoxymethyl-5-hydroxy-4H-pyran -4-one, kojic acid glycoside, geranylgeranylacetone, kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, kojic acid monostearate, kojic acid monocinnamate, kojic acid monobenzoate, kojic acid dibutyrate , Kojic acid dipalmitate, kojic acid distearate, kojic acid dioleate, etc.), oxybenzone, benzophenone, gua Iazulene, shikonin, baicalin or salts thereof and derivatives thereof, baicalein or salts thereof and derivatives thereof, berberine or salts thereof and derivatives thereof, chrysin or salts thereof and derivatives thereof, apigenin or salts thereof and derivatives thereof, luteolin Or salts thereof and derivatives thereof, acacetin or salts thereof and derivatives thereof, diosmethine or salts thereof and derivatives thereof, kaempferol or salts thereof and derivatives thereof, triphorin or salts thereof and derivatives thereof, astragalin or salts thereof And derivatives thereof, quercetin or salts thereof and derivatives thereof, quercitrin or salts thereof and derivatives thereof, isoquercitrin or salts thereof and derivatives thereof, rutin or salts thereof and derivatives thereof. Body, morin or a salt thereof and derivatives thereof, myricetin or a salt thereof and derivatives thereof, myricitrin or a salt thereof and derivatives thereof, datiscetin or a salt thereof and derivatives thereof, quercetagetin or a salt thereof and derivatives thereof, isorhamnetin or Salts thereof and derivatives thereof, pinocembrin or salts thereof and derivatives thereof, naringenin or salts thereof and derivatives thereof, hesperetin or salts thereof and derivatives thereof, eriodictyol or salts thereof and derivatives thereof, pinobankin or salts thereof and Derivatives thereof, aromadendrin or a salt thereof and derivatives thereof, engelitin or a salt thereof and derivatives thereof, taxofolin or a salt thereof and derivatives thereof, astilbine or a salt thereof and the same Derivatives, amperopsin or salts thereof and derivatives thereof, spiraeoside, kaempferol-7-neohesperidoside, glutathione or salts thereof and derivatives thereof, isoflavone glycosides (6-o-apiosylpuerarin-4'-o -Glucosides, 6-o-glucosyl puerarin, 3'-hydroxy puerarin-4'-o-glucoside, 6-o-apiosyl-3'-hydroxy puerarin), γ-pyrone glycosides (maltol-3-o-) (6'-o-apiosyl) -glucoside, maltol-3-o- (6'-o-apiosyl) -glucoside, etc.), isononyl ferrate, ellagic acid or salts thereof and derivatives thereof (5,4-dimethyl) Ellagic acid, 3,3'-dimethylellagic acid, 3,3 ', 4-trimethylellagic acid, 3,3', 4,4'-tetramethyl-5-methoxyellagic acid, 3-ethyl-4-methyl- 5-hydroxy ellagic acid, amritoside, etc.), lucinol, ON Saponin, Bacmond saponin, ruscogenin, sericoside, asiaticoside, hederin, senegin, benzoic acid anilides (4-hydroxy-N- (2-hydroxyphenyl) benzoic acid amide, 4-hydroxy-N- (3-hydroxyphenyl) ) Benzamide, 4-hydroxy-N- (4-hydroxyphenyl) benzamide, 3,5-di-t-butyl-4-hydroxy-N- (4-hydroxyphenyl) benzamide, 3,5-di-t-butyl -4-hydroxy-N- (3-hydroxyphenyl) benzamide, 3,5-di-t-butyl-4-hydroxy-N- (2-hydroxyphenyl) benzamide, etc.), diphenylpyralin, cyproheptadine, triprolidine, dimethindene , Ozagrel, istipendil, iproheptin, homochlorcyclidine, alimemazine, bucillamine, oxytosamide, vidarabine, xanthotoxin Sole, phenylmercury hexachlorophene, mercuric oxide, mercuric chloride, hydrogen peroxide, zinc peroxide, placenta (bovine origin, pig origin, horse origin, sheep origin, etc.) extract, almond extract Ammarok Extract, Oyster Extract, Ovana Okella Extract, Ochera Extract, Konfuyo Extract, Uncaria Extract, Gaijicha Extract, Gypsophila Extract, Licorice Extract, Gardenia Extract, Kranigean Extract, Clara Extract, Koganebana (Ogon) ) Extract, wheat (wheat) extract, rice (rice) extract, Koreaia extract, Sidwaya extract, sun cucumber extract, sanvitro extract, sun pens extract, silane (bikkyu) extract, senkyu (river cucumber) extract, senna extract, sempukuka extract , Senkutsusai extract, Su Rigatin extract, Nodake (mae-hu) extract, pearl barley (yokuinin) extract, hamago extract, honey beetle extract, hamamelis extract, palm extract, parietalia extract, safflower (safflower) extract, mugwa (mulberry bark) ) Extract, malvanojadin (bitter gins) extract, purple squirrel extract, white squirrels extract, mugwort mugwort extract, yashajitsu extract, hongkong extract, bituminous (ground) extract, quail lily extract, scallop extract, scorpion extract and the like.

(2) Tyrosinase activity inhibitors Specifically, ascorbic acid or a salt thereof and derivatives thereof (phosphate-L-magnesium ascorbate, ascorbyl palmitate, ascorbyl dipalmitate, hydroxyprophosphate phosphate ascorbate, 5- o-α-D-Glucopyranosyl-L-ascorbic acid, L-ascorbic acid phosphate sodium salt, L-ascorbic acid phosphate potassium salt, L-ascorbic acid phosphate magnesium salt, L-ascorbic acid phosphate Calcium salt, L-ascorbic acid phosphate aluminum salt, L-ascorbic acid sulfate sodium salt, L-ascorbic acid sulfate potassium salt, L-ascorbic acid sulfate magnesium salt, L-ascorbic acid sulfate calcium salt, L -Ascorbic acid sulfate Stell aluminum salt, L-ascorbic acid sodium salt, L-ascorbic acid potassium salt, L-ascorbic acid magnesium salt, L-ascorbic acid calcium salt, L-ascorbic acid aluminum salt, 6-o-α-D-galactopyrano Sil-L-ascorbic acid, 2-o-β-D-galactopyranosyl-L-ascorbic acid, L-ascorbic acid phosphate magnesium salt, L-ascorbic acid phosphate sodium salt, L-ascorbic acid sulfate Ester sodium salt, 6-o-acyl ascorbic acid phosphate sodium salt, 6-o-acyl ascorbic acid phosphate ammonium salt, 6-o-acyl ascorbic acid phosphate isopropanolamine salt, 3-o-isopropyl- L-ascorbic acid, 6-o-alkylascorbic acid potassium ester potassium salt, 6-o-alkylascorbic acid phosphate Steal calcium salt, 6-o-alkyl ascorbic acid phosphate barium salt, 6-o-alkyl ascorbic acid phosphate ammonium salt, 6-o-alkyl ascorbic acid phosphate monoethanolamine salt, 6-o-alkyl Ascorbic acid phosphate diethanolamine salt, 6-o-alkylascorbic acid phosphate triethanolamine salt, 6-o-alkylascorbic acid phosphate monoisopropanolamine salt, 6-o-alkylascorbic acid phosphate diisopropanol Amine salt, 6-o-alkylascorbic acid phosphate triisopropanolamine salt, 3-o-glycosyl-L-ascorbic acid, 6-o-β-D-galactopyranosyl-L-ascorbic acid, phosphorus ascorbate Acid cholesterol ester, palmitic acid-L-ascorbyl, isopa Mycinic acid-L-ascorbyl, dipalmitic acid-L-ascorbyl, diisopalmitic acid-L-ascorbyl, stearic acid-L-ascorbyl, isostearic acid-L-ascorbyl, distearic acid-L-ascorbyl, diisostearic acid-L- Ascorbyl, myristic acid-L-ascorbyl, isomyristic acid-L-ascorbyl, dimyristic acid-L-ascorbyl, diisomyristic acid-L-ascorbyl, 2-ethylhexanoic acid-L-ascorbyl, di-2-ethylhexane Acid-L-ascorbyl, oleic acid-L-ascorbic acid, 2-o-α-D-glucosyl-L-ascorbic acid, 2-o-α-D-maltosyl-L-ascorbic acid, 2-o-α- D-maltotriosyl-L-ascorbic acid, 3-o-α-D-glucosyl-L-ascorbic acid, 2-o-α-D-maltosyl-L-ascorbic acid, 2-o-α-D-malto Triosyl-L-ascorbic acid, L-ascorbic acid Trisopalmitic acid ester, L-ascorbic acid tetralauric acid ester, L-ascorbic acid tetra-2-ethylhexanoic acid ester, L-ascorbic acid tetraoleic acid ester, 5,6-isopropylidene-L-ascorbic acid, L- Ascorbic acid retinol ester, L-ascorbic acid-DL-tocopherol phosphate ester, L-3-o-ethylascorbic acid, L-ascorbic acid tristearate, L-ascorbic acid tripalmitate, L-ascorbic acid trioleate, L-ascorbyl triphosphate, 2-o-ascorbyl cinnamate, 2-o-ascorbyl ferrate, 2-o-ascorbyl caffeate, 2-o-ascorbyl cinnamate, 2-o- [6-palmitoyl ascorbyl] -4'-acetoxyferrate, DL-α-tocopherol-2-L-ascorbic acid phosphoric acid diester, Scorbic acid inositol-linked derivatives, ascorbic acid phosphoramide derivatives, ascorbic acid arbutin conjugates, ascorbyl phosphoryl cholesterol, chromanyl ascorbic acid derivatives, ascorbic acid sialic acid derivatives, etc.), hydroquinone or its salts and their derivatives (hydroquinone α-D-glucose) , Hydroquinone β-D-glucose, hydroquinone α-L-glucose, hydroquinone β-L-glucose, hydroquinone α-D-galactose, hydroquinone β-D-galactose, hydroquinone α-L-galactose, hydroquinone β-L-galactose, etc. Hexoses, hydroquinone α-D-ribose, hydroquinone β-D-ribose, hydroquinone α-L-ribose, hydroquinone β-L-ribose, hydroquinone α-D-arabinose, hydroquinone β-D -Five carbon sugar glycosides such as arabinose, hydroquinone α-L-arabinose, hydroquinone β-L-arabinose, hydroquinone α-D-glucosamine, hydroquinone β-D-glucosamine, hydroquinone α-L-glucosamine, hydroquinone β-L -Amino sugar glycosides such as glucosamine, hydroquinone α-D-galactosamine, hydroquinone β-D-galactosamine, hydroquinone α-L-galactosamine, hydroquinone β-L-galactosamine, hydroquinone α-D-glucuronic acid, hydroquinone β-D -Glucuronic acid, hydroquinone α-L-glucuronic acid, hydroquinone β-L-glucuronic acid, hydroquinone α-D-galacturonic acid, hydroquinone β-D-galacturonic acid, hydroquinone α-L-galacturonic acid, hydroquinone β-L-galacturon Hydroquinone glycosides such as uronic acid glycosides such as acids Body, hydroquinone benzyl ether, 4-β-D-glucopyranosyloxy-1- (4-hydroxyphenoxy) butane, 5-β-D-glucopyranosyloxy-1- (4-hydroxyphenoxy) pentane, 6-β-D-glucopyranosyloxy-1- (4-hydroxyphenoxy) hexane, 2-β-D-glucopyranosyloxy-1- (4-hydroxyphenoxy) propane, 2-β-D- Hydroquinone hydroxyalkyl ether glycosides such as glucopyranosyloxy-1- (4-hydroxyphenoxy) butane and 2-β-D-glucopyranosyloxy-1- (4-hydroxyphenoxy) propan-3-ol ), Kojic acid or a salt thereof and derivatives thereof (2-methoxymethyl-hydroxy-4H-pyran-4-one, 2-ethoxymethyl-5-hydroxy-4H-pyran-4-one, 2-benzoluyloxy Methyl-5-hydroxy-4H-pyran-4-one, 2-cinna Iroxymethyl-5-hydroxy-4H-pyran-4-one, 2-phenoxymethyl-5-hydroxy-4H-pyran-4-one, kojic acid glycoside, geranylgeranylacetone, kojic acid monobutyrate, kojic acid monocaprate , Kojic acid monopalmitate, kojic acid monostearate, kojic acid monocinnamate, kojic acid monobenzoate, kojic acid dibutyrate, kojic acid dipalmitate, kojic acid distearate, kojic acid dioleate, etc.), tocopherol or salts thereof and derivatives thereof (Α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, ε-tocopherol, α-tocopheryl retinoate, aminomethylated tocopherol, hydroxymethylated tocopherol, tocopheryl phosphate, tocopherol acetate, tocopherol Errol nicotinate, tocopherol succinate, tocopherol linoleate, tocopherol orotate, DL-α-tocopheryl glucoside, DL-α-tocopheryl maltoside, DL-β-tocopheryl glucoside, DL-β-tocopheryl maltoside DL-γ-tocopheryl glucoside, DL-γ-tocopheryl maltoside, DL-δ-tocopheryl glucoside, DL-δ-tocopheryl maltoside, D-α-tocopheryl glucoside, D-α-tocopheryl maltoside Sid, D-β-tocopheryl glucoside, D-β-tocopheryl maltoside, D-γ-tocopheryl glucoside, D-γ-tocopheryl maltoside, D-δ-tocopheryl glucoside, D-δ-tocopheryl Maltoside, L-α-tocopheryl glucoside, L-α-tocopheryl maltoside, L-β-tocopheryl glucoside, L-β-tocopheryl maltoside, L-γ-tocov Lyl glucoside, L-γ-tocopheryl maltoside, L-δ-tocopheryl glucoside, L-δ-tocopheryl maltoside, L- (sulfoethylamino) -3- (α-tocopheryl-6-iroxy) Propan-2-ol, 1- (carboxypropylamino) -3- (α-tocopheryl-6-iroxy) propan-2-ol hydrochloride, S- [3- (α-tocopheryl-6-iroxy ) -2-Hydroxypropyl] cysteine, S- [3- (α-tocopheryl-6-yloxy) -2-hydroxypropyl] -γ-glutamylcystenylglycine, N- [3- (α-tocopheryl) -6-Iroxy) -2-hydroxypropyl] aspartic acid, N- [3- (α-tocopheryl-6-iroxy) -2-hydroxypropyl] glutamic acid, etc.), tocotrienol or a salt thereof and derivatives thereof (α -Tocotrienol, β-Tocotrienol, γ-Toco Lienol, δ-tocotrienol, tocotrienol acetate, tocotrienol nicotinate, tocotrienol succinate, tocotrienol linoleate, tocotrienol orotate), N-acetyltyrosine or a salt thereof and derivatives thereof, glutathione or a salt thereof and derivatives thereof, ellagic acid Or a salt thereof and a derivative thereof (3,4-dimethylellagic acid, 3,3′-dimethylellagic acid, 3,3 ′, 4-trimethylellagic acid, 3,3 ′, 4,4′-tetramethyl-5 -Methoxyellagic acid, 3-ethyl-4-methyl-5-hydroxyellagic acid, amritoside, etc.), isonitrine A, isonitrine B, isonitrine C, isonitrine D, isonitrinic acid E, isonitrinic acid F, dermadein, tricobylidein, etc. Isonitrile antibiotics, orselinic acid derivatives (orceric acid, Ruthenic acid ethyl ester orcinol, p-geranylorceric acid, p-geranylorceric acid ethyl ester geranylorcinol, p-farnesylorselinic acid, p-farnesylorselinic acid ethylester farnesylorcinol, p-dodecanylol Serine acid, p-dodecanylorceric acid ethyl ester dodecanylorcinol, p-tetradecanylorceric acid, p-tetradecanylorceric acid ethylester tetradecanylorcinol, p-hexadecanylorceric acid P-hexadecanylorceric acid ethyl ester hexadecanylorcinol, p-undecanylorceric acid, p-undecanylorceric acid ethylester undecanylorcinol, p-tridecanylorceric acid, p-Tridecanylorceric acid ethyl ester undecanyl Orcinol, p-pentadecanylorceric acid, p-pentadecanylorceric acid ethyl ester pentadecanylorcinol, ethylhexylorceric acid, p-ethylhexylorceric acid ethylester ethylhexylorcinol, p-cyclohexylmethylorserine Acid, p-cyclohexylmethylorceric acid ethyl ester cyclohexylmethylorcinol, p-hydroxyethylhexylorceric acid methyl ester, p-hydroxyethylhexylorceric acid hydroxyethylhexylorcinol, etc.), umbelic acid, brefeldin, oxydesvera Trol, resorcinol derivative (4-cyclohexylresorcinol), 3-hydroxyketone compound (1,5-bis (p-hydroxyphenyl) -2-hydroxypentan-4-one, 1,5-bis (o, p-di) Droxyphenyl) -2-hydroxypentan-4-one, 1,5-bis (p-hydroxyphenyl-m-methoxyphenyl) -2-hydroxypentan-4-one, etc.), 1,3-diketone compounds (1 , 5-bis (p-hydroxyphenyl) -2,4-pentanedione, 1,5-bis (o, p-dihydroxyphenyl) -2,4-pentanedione, 1,5-bis (p-hydroxyphenyl- m-methoxyphenyl) -2,4-pentanedione), bishydroxybenzyl amides, γ-aminobutyric acid or its derivatives (N-methyl-γ-aminobutyric acid, N-dimethyl-γ-aminobutyric acid, γ-amino) Butyric acid oleyl ester, etc.), hydrogen peroxide, zinc peroxide, placenta extract, lucinol, silk extract, acacia extract, acerola extract, ichibi (winter position) extract, weeping birch extract, quellus extract, chestnut extract, kameba hikokoshi extract , Kuroba Nahi-Kokoshi extract, Toki-shiki (life-extending grass) extract, Seri extract, buckwheat extract, Davilia extract, Nazuna extract, Fujiba kama (Orchid grass) extract, chamomile extract, mulberry extract, gardenia extract, Japanese cypress extract, burnet extract, clara extract, mugwort extract, honeysuckle extract , Yellowfin extract, dokudami extract, pine-hodo extract, barley extract, scotch extract, hop extract, hawthorn extract, eucalyptus extract, yarrow extract, altea extract, cinnamon extract, mandarin extract, hamamelis extract, yamagwa extract, bellflower extract, toshishi extract, continued Suicho extract, sprayed extract, maize extract, senkyu extract, dokkatsu extract, psycho extract, boufu extract, kingfish extract, oxon extract, peony skin extract Peony extract, Geranium thunbergii extract, kudzu root extract, licorice extract, gallnut extract, aloe extract, Cimicifuga extract, safflower extract, green tea extract, black tea extract, include Uncaria gambir Roxburgh extract, and the like.

(3) Melanocyte melanin production inhibitor
Specifically, lobeline or lobeline derivatives, liquiritin derivatives (eg, liquiritin-α-glucoside, liquiritin-α-maltoside, etc.), phenylchroman derivatives, chromone derivatives (2-butylchromone, 2-pentylchromone, 2-heptylchromone, 2 -Nonylchromone, 2-hexadecylchromone, 2- (1-ethylpentyl) chromone, 2-butyl-7-methoxychromone, 2-pentyl-7-methoxychromone, 2-heptyl-7-methoxychromone, 2-nonyl- 7-methoxychromone, 2-pentadecyl-7-methoxychromone, 2- (1-ethylpentyl) -7-methoxychromone, 7-hydroxy-2-methylchromone, 7-hydroxy-2-butylchromone, 7-hydroxy- 2-pentylchromone, 7-hydroxy-2-heptylchromone, 7-hydroxy-2-nonylchromone, 7-hydroxy-2-pentadecylchromone, 7-hydro Cis-2- (1-ethylpentyl) chromone), azelaic acid derivatives (azelaic acid monoalkyl ester, azelaic acid dialkyl ester, etc.), phosphatidylglucosamine, lysophosphatidylglucosamine, phenylhydroquinone, 3-β-D-glucopyrano Silmanur, 3-β-D-maltopyranosylmanur, substituted amino acid derivatives (DL-N-formyl-3- (1-naphthyl) alanine, DL-N-acetyl-3- (1-naphthyl) alanine, DL -N-propionyl-3- (1-naphthyl) alanine, DL-N-butyryl-3- (1-naphthyl) alanine, DL-N-isobutyryl-3- (1-naphthyl) alanine, DL-N-valeryl- 3- (1-naphthyl) alanine, DL-N-isovaleryl-3- (1-naphthyl) alanine, DL-N- (2-methylvaleryl) -3- (1-naphthyl) alanine, DL-N- (3- Methyl valeryl) -3- (1-naphthyl) alanine, DL-N- (4-methyl) Ruvalyl) -3- (1-naphthyl) alanine, DL-N-t-butylacetyl-3- (1-naphthyl) alanine, DL-N-pivaloyl-3- (1-naphthyl) alanine, DL-N-caproyl -3- (1-naphthyl) alanine, DL-N- (2-ethylhexanoyl) -3- (1-naphthyl) alanine, DL-N- (2-methylhexanoyl) -3- (1-naphthyl) Alanine, DL-N-Heptanoyl-3- (1-naphthyl) alanine, DL-N-octanoyl-3- (1-naphthyl) alanine, DL-N- (2-propylpentanoyl) -3- (1-naphthyl) ) Alanine, DL-N-nonanoyl-3- (1-naphthyl) alanine, DL-N-decanoyl-3- (1-naphthyl) alanine, DL-N-undecanoyl-3- (1-naphthyl) alanine, DL- N-dodecanoyl-3- (1-naphthyl) alanine, DL-N-tridecanoyl-3- (1-naphthyl) alanine, DL-N-tetradecanoyl-3- (1-naphthyl) alanine, DL-N-pentadecanoy -3- (1-naphthyl) alanine, DL-N-hexadecanoyl-3- (1-naphthyl) alanine, DL-N-heptadecanoyl-3- (1-naphthyl) alanine, DL-N-octadecanoyl- 3- (1-naphthyl) alanine, DL-N-nonadecanoyl-DL-3- (1-naphthyl) alanine, DL-N-icosanoyl-3- (1-naphthyl) alanine, DL-N-acroyl-3- ( 1-naphthyl) alanine, DL-N-crotoniloyl-3- (1-naphthyl) alanine, DL-N-methacryloyl-3- (1-naphthyl) alanine, DL-N-vinylacetyl-3- (1-naphthyl) Alanine, DL-N-cyclopropanoyl-3- (1-naphthyl) alanine, DL-N- (2-pentenoyl) -3- (1-naphthyl) alanine, DL-N- (4-pentenoyl) -3- (1-naphthyl) alanine, DL-N- (2-hexenoyl) -3- (1-naphthyl) alanine, DL-N- (3-hexenoyl) -3- (1-naphthyl) alanine, DL-N- ( 2-methyl-3-pente Yl) -3- (1-naphthyl) alanine, DL-N-cyclohexenoyl-3- (1-naphthyl) alanine, DL-N- (10-undecenoyl) -3- (1-naphthyl) alanine, DL-N-linoleyl-3- (1-naphthyl) alanine, DL-N-hydroxyacetyl-3- (1-naphthyl) alanine, DL-N- (6-hydroxycaproyl) -3- (1-naphthyl) Alanine, DL-N- (8-hydroxyoctanoyl) -3- (1-naphthyl) alanine, DL-N- (9-hydroxynonanoyl) -3- (1-naphthyl) alanine, DL-N- (10 -Hydroxydecanoyl) -3- (1-naphthyl) alanine, DL-N- (11-hydroxyundecanoyl) -3- (1-naphthyl) alanine, DL-N- (12-hydroxydecanoyl) -3 -(1-naphthyl) alanine, DL-N-benzoyl-3- (1-naphthyl) alanine, DL-N- (2-hydroxybenzoyl) -3- (1-naphthyl) alanine, DL-N- (3- Hydroxybenzoyl -3- (1-naphthyl) alanine, DL-N- (4-hydroxybenzoyl) -3- (1-naphthyl) alanine, DL-N- (o-toluyl) -3- (1-naphthyl) alanine, DL -N- (m-toluyl) -3- (1-naphthyl) alanine, DL-N- (p-toluyl) -3- (1-naphthyl) alanine, DL-N- (1-naphthoyl) -3- ( 1-naphthyl) alanine, DL-N- (2-naphthoyl) -3- (1-naphthyl) alanine, DL-N- (2-carboxybenzoyl) -3- (1-naphthyl) alanine, DL-N- ( 3-carboxybenzoyl) -3- (1-naphthyl) alanine, DL-N- (4-carboxybenzoyl) -3- (1-naphthyl) alanine, DL-N- (2-picoryl) -3- (1- Naphthyl) alanine, DL-N- (3-picolyloyl) -3- (1-naphthyl) alanine, DL-N- (4-picolyloyl) -3- (1-naphthyl) alanine, DL-N-phenylacetyl-3 -(1-Naphthyl) alanine, DL-N- (2-Phenylpropanoyl -3- (1-naphthyl) alanine, DL-N- (3-phenylbutyryl) -3- (1-naphthyl) alanine, DL-N- (4-methylvaleryl) -3- (1-naphthyl) alanine, DL-N-valeryl-3- (1-naphthyl) alanine, DL-N- (4-methylvaleryl) -3- (1-naphthyl) alaninamide, DL-N- (4-methylvaleryl) -3- (1- Naphthyl) alanine methyl ester, DL-N- (4-methylvaleryl) -3- (1-naphthyl) alanine ethyl ester, DL-N- (4-methylvaleryl) -3- (1-naphthyl) alanine propyl ester, DL- N- (4-methylvaleryl) -3- (1-naphthyl) alanine-N-butyl ester, DL-N- (4-methylvaleryl) -3- (1-naphthyl) alanine pentyl ester, DL-N- (4- Methylvaleryl) -3- (1-naphthyl) alanine isopropyl ester, DL-N- (4-methylvaleryl) -3- (1-naphthyl) alanine isobutyl ester, DL-N- (4-methylvaleryl) -3- (1-naphthyl) alanine-t-butyl ester, etc.), benzolactam derivatives, indolactam derivatives, cedrol, guaiool, 1- (4-hydroxyphenithio) -2- Propanol, β-lactoglobulin, 2-methoxy-5-methylphenol, 5-ethyl-2-methoxyphenol, 5-N-propyl-2-methoxyphenol, 5-N-butyl-2-methoxyphenol, 5-N -Hexyl-2-methoxyphenol, 5-N-heptyl-2-methoxyphenol, 5-N-decyl-2-methoxyphenol, 5- (1,1-dimethylpropyl) -2-methoxyphenol, 5- (1 , 1-dimethylbutyl) -2-methoxyphenol, 5- (1,1-dimethylethyl) -2-methoxyphenol, 2-methoxy-5- (1-methylpentyl) phenol, 2-methoxy-5- (1 -Methylhexyl) phenol, 2-methoxy-5- (3-methylhexyl) ) Phenol, 2-methoxy-5- (6-methylheptyl) phenol, 5- (1,3-dimethylheptyl) -2-methoxyphenol, malvelin, ferguinol, sugiol, cryptojaponol, 1,5-bis [p -Hydroxyphenyl] -1,4-pentadien-3-one, 1,5-bis [o-hydroxyphenyl] -1,4-pentadien-3-one, 1,5-bis [2,4-dihydroxyphenyl] ] -1,4-pentadien-3-one, 1,5-bis [3-methoxy-4-hydroxyphenyl] -1,4-pentadien-3-one, haginin, agrimophor, agrimol, hydrangenol or its Derivatives, alkylresorcinol or its derivatives (such as 4-N-butylresorcinol), aristolone, caramenene (such as caramenene, 7-hydroxycaramenene, 5-hydroxycaramenene, 7-methoxycaramenene), trans-umbe Acid, N-α-benzoyl-L-arginine, N-α-benzoyl-L-arginine ethyl ester or N-α-benzoyl-L-arginine ethyl ester, 5-methyl-2 (3H) -furanone, 2-butene -4-Orido, 2-hydroxymethylfuran, 2,5-dimethyl-4-hydroxy-3 (2H) -furanone, 2-formylfuran, 3-formylfuran, methyl α-furyl ketone, furfuryl acetate, 2-hydroxy -3-methyl-2-cyclopenten-1-one, 2-hydroxy-3,5-dimethyl-2-cyclopenten-1-one, 2,5-dimethyl-4-hydroxy-3 (2H) -thiophenone, 2- Hydroxy-3-ethyl-2-cyclopenten-1-one, tetronic acid, pentanedione, iminodibenzyls (2,2'-iminodibenzyl, imipramine, imipramine hydrochloride, desipramine, desipramine hydrochloride, chlorimipramine, trimipramine, etc. ), Dibenzocyclohe Tadienes (amitriptyline, amitriptyline hydrochloride, nortriptyline, noxiptylline, etc.), tetrahydrocopalol glycosides (ketotifen fumarate, labda-8 (17), 13-dien-15-ol, tetrahydromanol, tetrahydrocoparol, tetrahydro Copalol glucoside, tetrahydrocoparol galactoside, tetrahydrocoparol maltoside, tetrahydrocoparol cellobioside, tetrahydrocoparol maltotrioside, etc.), spiro ether compound, piokerin, phenothiazine compound, promethazine, alimemazine, alimemazine tartrate, triflupromazine , Levomepromazine, chlorpromazine, cyclandrate, 4-carboxymethyloxybenzoic acid, 4-carboxymethyloxy-2-hydroxybenzoic acid, 3- (3- Ruboxypropyl-1-oxy) -2-hydroxybenzoic acid, 4- (3-carboxypropyl-1-oxy) benzoic acid, 4- (3-carboxypropyl-1-oxy) -2-hydroxybenzoic acid, 4 -(3-carboxypropyl-1-oxy) -2-methoxybenzoic acid, 5- (3-carboxypropyl-1-oxy) -2-hydroxybenzoic acid, 4- (5-carboxypentyl-1-oxy)- 2-hydroxybenzoic acid, 6- (3-carboxypropyl-1-oxy) -2-hydroxybenzoic acid, 4- (10-carboxydecane-1-oxy) -2-hydroxybenzoic acid, 4- (10-carbamoyl) Decan-1-oxy) -2-hydroxybenzoic acid, 4- (4-hydroxybutyl-1-oxy) benzoic acid, 4- (4-hydroxybutyl-1-oxy) -2-hydroxybenzoic acid, 4- ( 4-acetoxybutyl-1-oxy) benzoic acid, 4- (4-acetoxybutyl-1-oxy) -2-hydroxybenzoic acid, 4- (3-etho Cycarbonylpropyl-1-oxy) -2-hydroxybenzoic acid, 3- (2,3-dihydroxypropyl-1-oxy) -2-hydroxybenzoic acid, 4- (4-methoxybutyl-1-oxy) -2 -Hydroxybenzoic acid, 4- (2,3-dihydroxypropyl-1-oxy) -2-hydroxybenzoic acid, 4-carboxymethyloxy-2-hydroxybenzoic acid, 3- (3-carboxypropyl-1-oxy) 2-hydroxybenzoic acid, 4- (3-carboxypropyl-1-oxy) -2-hydroxybenzoic acid, 5- (3-carboxypropyl-1-oxy) -2-hydroxybenzoic acid, 6- (3- Carboxypropyl-1-oxy) -2-hydroxybenzoic acid, 4- (5-carboxypentyl-1-oxy) -2-hydroxybenzoic acid, 4- (4-hydroxybutyl-1-oxy) -2-hydroxybenzoic acid Acid, 4- (10-carboxydecane-1-oxy) -2-hydroxybenzoic acid, hydroxytrimethyl Cyclohexanes (2-hydroxy-4- (2,2,6-trimethyl-1-yl-cyclohexane) butane, 4- (2,2,6-trimethyl-1-yl-cyclohexane) -1-butene, 4- (2,2,6-trimethyl-1-yl-cyclohexane) -2-butene, 4- (2,2,6-trimethyl-1-yl-cyclohexane) butane, 3-methyl-3-hydroxy-5- ( 2,2,6-trimethyl-1-yl-cyclohexane) pentane, 3-methyl-1-hydroxy-5- (2,2,6-trimethyl-1-yl-cyclohexane) pentane, 3-methyl-5- ( 2,2,6-trimethyl-1-yl-cyclohexane) pentane, 3-methyl-1-hydroxy-5- (2,2,6-trimethyl-1-yl-cyclohexane) -3-pentene, 3-methyl- 3-Hydroxy-5- (2,2,6-trimethyl-1-yl-cyclohexane) -1-pentene, 3-methyl-1-hydroxy-5- (2,2,6-trimethyl-1-yl-cyclohexane ) -2-Pentene, 2-Hydroxy-4 -(2,2,6-trimethyl-1-yl-cyclohexane) butane and other monosaccharides, disaccharides or trisaccharide glycosides), escinol, parahydroxycinnamic acid-4- (2,2,6-trimethyl) -Yl-cyclohexane) -2-butyl ester monosaccharide, disaccharide or trisaccharide glycoside, ondisaponin, bacmond saponin, ruscogenin, sericoside, asiaticoside, hederin, senegin, 4- (2,2,6 -Torime
Tyl-1-yl-cyclohexane) -2-keto-butane, 4- (2,2,6-trimethyl-1-yl-6-cyclohexene) -2-keto-butane, 4- (2,2,6- Trimethyl-1-yl-cyclohexane) -2-keto-3-butene, 4- (2,2,6-trimethyl-1-yl-6-cyclohexene) -2-keto-3-butene (β-ionone), Lp-hydroxyphenylglycine, Dp-hydroxyphenylglycine, N-benzyloxycarbonyl-Lp-hydroxyphenylglycine, N-benzyloxycarbonyl-Dp-hydroxyphenylglycine, N-benzoyl-Lp-hydroxyphenylglycine, N-benzoyl- Dp-hydroxyphenylglycine, N- (p-methoxybenzoyl) -Lp-hydroxyphenylglycine, N- (p-methoxybenzoyl) -Dp-hydroxyphenylglycine, N- (p-hydroxybenzoyl) -Lp-hydroxyphenylglycine , N- (p-hydroxybe Nzoyl) -Dp-hydroxyphenylglycine, N-acetyl-Lp-hydroxyphenylglycine, N-acetyl-Dp-hydroxyphenylglycine, N-acetyl-Lp-hydroxyphenylglycine ethyl ester, N-acetyl-Dp-hydroxyphenylglycine Ethyl ester, N-acetyl-Lp-hydroxyphenylglycinamide, N-acetyl-Dp-hydroxyphenylglycinamide, Lp-methoxyphenylglycine, Dp-methoxyphenylglycine, Lp-methoxyphenylglycine hydrochloride, Dp-methoxyphenylglycine Hydrochloride, 4-hydroxy-3-methoxy-L-phenylglycine, 4-hydroxy-3-methoxy-D-phenylglycine, Lp-hydroxyphenylglycine ethylamide, Dp-hydroxyphenylglycine ethylamide, N-tert-butoxy Carbonyl-Lp-hydroxyphenylglycine, N -tert-butoxycarbonyl-Dp-hydroxyphenylglycine, N-tert-butoxycarbonyl-Lp-methoxyphenylglycine, N-tert-butoxycarbonyl-Dp-methoxyphenylglycine, N-9-fluorenylmethyloxycarbonyl-Lp -Methoxyphenylglycine, N-9-fluorenylmethyloxycarbonyl-Dp-methoxyphenylglycine, N-9-fluorenylmethyloxycarbonyl-Lp-methoxyphenylglycine benzyl ester hydrochloride, N-9-fluorenyl Methyloxycarbonyl-Dp-methoxyphenylglycine benzyl ester hydrochloride, Lp-hydroxyphenylglycinamide, Dp-hydroxyphenylglycine amide, Lp-hydroxyphenylglycine allyl ester p-toluenesulfonate, Dp-hydroxyphenylglycine allyl ester p -Toluenesulfonate, Lp- Droxyphenylglycine benzyl ester p-toluenesulfonate, Dp-hydroxyphenylglycine benzyl ester p-toluenesulfonate, Lp-hydroxyphenylglycine ethyl ester, Dp-hydroxyphenylglycine ethyl ester, Lp-hydroxyphenylglycine ethyl ester Hydrochloride, Dp-hydroxyphenyl glycine ethyl ester hydrochloride, Lp-hydroxyphenyl glycine methyl ester, Dp-hydroxyphenyl glycine methyl ester, etc., 1,3-diallylindane-2-carboxylic acids, stachybosines, pheophorbide derivatives, eleucerin, Isoeleucerin or 4-β-hydroxyisoereucerine, eleucerinol, spiroketal derivatives (2- (2,4-hexadinylidene) -1,6-dioxaspiro [4.5] dec-3-ene, 2- (2-hexynyl ) -1,6-dioxaspiro [4.4] non-3-ene, 2-((4-methylphenyl) methylidene) -6,6-dioxaspiro [4.4] non-3-ene, 2- (2-hexenylidene) -6,6-Dioxaspiro [4.5] dec-3-ene, 2- (2-hexenylidene) -1,6-dioxaspiro [4.4] non-3-ene, 2-hexyl-1,6-dioxaspiro [4.4] nonane 2- (2-hexenyl) -1,6-dioxaspiro [4.4] nonane, 2- (2-hexynyl) -1,6-dioxaspiro [4.4] nonane, 2-pentyl-1,6-dioxaspiro [4.4] nonane 1,6-dioxaspiro [4.4] nonane, 1,6-dioxaspiro [4.5] decane, 1,7-dioxaspiro [5.5] undecane, 2,3-benzo-4,4-dimethyl-1,6-dioxaspiro [4.4 Nonane, 3,4-benzo-2-pentyl-1,6-dioxaspiro [4.4] nonane, 3,4-benzo-2-hexyl-1,6-dioxaspiro [4.4] nonane, 3,4-benzo-2 -Octyl-1 , 6-Dioxaspiro [4.4] nonane, 2-hexyl-9,9-dimethyl-1,6-dioxaspiro [4.4] nonane, 2- (2,4-hexadiynylidene) -1,6-dioxaspiro [4.4] nona -3-ene, etc.), malvalic acid, phosphonic acid derivatives or salts thereof, aspergillomalasmin, aminophosphonic acid derivatives or salts thereof, diphenhydramine or salts thereof, pregnenolone or derivatives thereof, lutein, farnesyl isopropanol derivatives, hexahydrofarnesyl acetone 4-benzoylamino-2-hydroxybenzoic acid, 5-benzoylamino-2-hydroxybenzoic acid, 4-benzoylaminobenzoic acid, 4- (1-naphthoylamino) -2-hydroxybenzoic acid, 5- (1 -Naphthoylamino) -2-hydroxybenzoic acid, 4- (2-naphthoylamino) -2-hydroxybenzoic acid, 5- (2-naphthoylamino) -2-hydroxybenzoic acid Acid, 4- (1-naphthoylamino) benzoic acid, 4- (2-naphthoylamino) benzoic acid, 4-phenylaminocarbonylbenzoic acid, 4-phenylaminocarbonyl-2-hydroxybenzoic acid, 5-phenylamino Carbonyl-2-hydroxybenzoic acid, 4- (1-naphthylaminocarbonyl) benzoic acid, 4- (1-naphthylaminocarbonyl) -2-hydroxybenzoic acid, 5- (1-naphthylaminocarbonyl) -2-hydroxybenzoic acid Acid, 4- (2-naphthylaminocarbonyl) benzoic acid, 4- (2-naphthylaminocarbonyl) -2-hydroxybenzoic acid, 5- (2-naphthylaminocarbonyl) -2-hydroxybenzoic acid, hexahydrofarnesyl isopropanol Derivatives, borneol-p-hydroxycinnamate glucoside, borneol-p-hydroxycinnamate maltoside, borneol-p-hydroxy Cinnamic acid ester maltotrioside, cinnamic acid-4- (2,2,6-trimethyl-yl-cyclohexane) -2-butyl ester derivative, 2,4-dihydroxybenzophenone, 1- (2,4-dihydroxyphenyl) -Ethanone (2 ', 4'-dihydroxyacetophenone), 1- (2,4-dihydroxyphenyl) -1-propanone (2', 4'-dihydroxypropiophenone), 1- (2,4-dihydroxyphenyl) -1-butanone, 1- (2,4-dihydroxyphenyl) -1-pentanone, 1- (2,4-dihydroxyphenyl) -1-hexanone, 1- (2,4-dihydroxyphenyl) -1-heptanone, 1- (2,4-dihydroxyphenyl) -1-octanone, 1- (2,4-dihydroxyphenyl) -1-nonanone, 1- (2,4-dihydroxyphenyl) -1-decanone, 1- (2, 4-dihydroxyphenyl) -1-undecanone, 1- (2,4-dihydroxyphenyl) -1-dodecanone, 1- (2,4- Dihydroxyphenyl) -1-tetradecanone, 1- (2,4-dihydroxyphenyl) -1-hexadecanone, 1- (2,4-dihydroxyphenyl) -1-octadecanone, 1- (2-hydroxy-4-methoxyphenyl) -Ethanone (2'-hydroxy-4'-methoxyacetophenone), 1- (2-hydroxy-4-methoxyphenyl) -1-propanone (2'-hydroxy-4'-methoxypropiophenone), 1- (2 -Hydroxy-4-methoxyphenyl) -1-butanone, 1- (2-hydroxy-4-methoxyphenyl) -1-pentanone, 1- (2-hydroxy-4-methoxyphenyl) -1-hexanone, 1- ( 2-hydroxy-4-methoxyphenyl) -1-heptanone, 1- (2-hydroxy-4-methoxyphenyl) -1-octanone, 1- (2-hydroxy-4-methoxyphenyl) -1-nonanone, 1- (2-hydroxy-4-methoxyphenyl) -1-decanone, 1- (2-hydroxy-4-methoxy) Ciphenyl) -1-undecanone, 1- (2-hydroxy-4-methoxyphenyl) -1-dodecanone, 1- (2-hydroxy-4-methoxyphenyl) -1-tetradecanone, 1- (2-hydroxy-4- Methoxyphenyl) -1-hexadecanone, 1- (2-hydroxy-4-methoxyphenyl) -1-octadecanone, 1- (4-hydroxy-2-methoxyphenyl) -ethanone (4'-hydroxy-2'-methoxyacetophenone) ), 1- (4-hydroxy-2-methoxyphenyl) -1-propanone (4'-hydroxy-2'-methoxypropiophenone), 1- (2,4-dimethoxyphenyl) -ethanone (2 ', 4 '-Dimethoxyacetophenone), 1- (2,4-dimethoxyphenyl) -1-propanone (2', 4'-dimethoxypropiophenone), lactone derivative (1,6-dioxaspiro [4.4] nonane-2,7- Dione, 1,6-dioxaspiro [4.5] decane-2,7-dione, 4-tridecanolide 4-dodecanolide, 4-undecanolide, 4-decanolide, 4-nonanolide, 4-octanolide, 4-heptanolide, 5-dodecanolide, 5-undecanolide, 5-decanolide, 5-nonanolide, 5-octanolide, 2-undecen-4- Orido, 2-Decene-4-Olide, 2-Nonene-4-Olide, 2-Heptene-4-Olide, 2-Undecen-5-Olide, 2-Decene-5-Olide, 2-Nonene-5-Olide, 2-octene-5-olide, 4-methyl-4-dodecanolide, 4-methyl-4-undecanolide, 4-methyl-4-decanolide, 4-methyl-4-nonanolide, 4-methyl-4-heptanolide, 5- Methyl-5-dodecanolide, 5-methyl-5-undecanolide, 5-methyl-5-decanolide, 5-methyl-5-nonanolide, 5-methyl-5-octanolide, 2-methoxycarbonyl-4-dodecanolide, 2-methoxy Carbonyl-4-undecanolide, 2-methoxycarbonyl-4-decanolide, 2-methoxycar Nyl-4-nonanolide, 2-methoxycarbonyl-4-heptanolide, 2-methoxycarbonyl-5-undecanolide, 2-methoxycarbonyl-5-decanolide, 2-methoxycarbonyl-5-nonanolide, 2-methoxycarbonyl-5-octanolide 2-allyl-4-undecanolide, 2-allyl-5-decanolide, 2-allyl-4-nonanolide, 2-pentyl-4-undecanolide, 2-pentyl-4-nonanolide, 2-methyl-4-undecanolide, 2 -Methyl-4-nonanolide, 2- (4-hydroxybutyl) -4-undecanolide, 2- (4-hydroxybutyl) -4-nonanolide, 2- (4-hydroxybutyl) -5-decanolide, 5-propyloxy -4-pentanolide, 5-allyloxy-4-pentanolide, 5- (2-hydroxyethoxy) -4-pentanolide, 8-hydroxy-4-octanolide, 6-propyloxy-5-hexanolide, 6-allyloxy-5-hexanolide , 6- (2- Hydroxyethoxy) -5-hexanolide, 9-hydroxy-5-nonanolide, etc.), ethinomycin, iriflorental, iriparidal, 2'-8-C-glucosyl-7-methylaloesol coumaroyl ester, 2'-8- C-Glucosyl-7-methyl aloesol cinnamoyl ester, chloropyramine, anise extract, aloe extract, itadori (tiger cane root) extract, seaweed extract, shrimp rush extract, ketsumeishi (Kameko) extract, sea urchin extract , Paramecium (calocon) extract, Onamomi (Tempura) extract, Oni Yagara (Tempa) extract, Oyster extract, Ginseng extract, Oyaku extract, Pumpkin extract, Gama (Yellow yellow) extract, Kansui extract, Kimizuki (Senkuru) Grass) extract, black moji extract, black spruce extract, sisal Sisal extract, Saximas button extract, Chinese button extract, Chinese ginseng extract, Oshima cherry extract, Oya cherry extract, Bean cherry extract, Takane cherry extract, Kohigan extract, Sato cherry extract, Zion extract, Shiro extract, Shirobana Iris extract, ginseng extract, potato beetle extract, diamondfish extract, primrose extract, toshishi extract, bean extract, Japanese pear extract, sagebrush extract, yarrow extract, dill extract, honey beetle extract, Clams extract, Hitotsuba (stone persimmon) extract, Himegama (cranberry) extract, peony extract, floral blanka extract, hamula extract, sagebrush extract, hill O extract, sandalwood extract, red mushroom extract (reishi mushroom extract), swordfish (beneficial herb) extract, river willow extract, red willow extract, cat willow extract, catfish willow extract, quince willow extract, cory willow extract, unryu willow extract, yama willow extract, weeping willow Willow extract, Chinese cabbage extract, Fox willow extract, Doronoki extract, Japanese yam extract, Agave mid-autumn, Aono Agave extract, Fu
Crested Agave Extract, Mitsumata Extract, Aonori Extract, Usubaaonori Extract, Susioonori Extract, Hiraaonori Extract, Bowuaonori Extract, Hosoeda Aonori Extract, Kombu Extract, Macombu Extract, Resilibum Extract, Hosome Kombu Extract, Mitsuishi Kombu Extract, Wakame Extract Aowakame extract, hijiki extract, hibamata extract, sea urchin extract, sea bass extract, sea bream water extract, red sea urchin extract, sea urchin extract, sea urchin extract, sea bass extract, sea urchin extract, seaweed extract Extract, giraffe rhinoceros extract, juniper ginseng rhinoceros extract, tsunomata extract, ibottsu nomata extract, malvatsu nomata extract, Lakotoji extract, Sugi nori extract, Shikinori extract, Kainori extract, Yakuzusa extract, Urabo shiyahaz extract, Umiuchiwa extract, Ishimozuku extract, Misjikonbu extract, Atsuba misji extract, Isomok extract, Nagashima mok extract, Shimomoku extract, Nemosa extract , Tatsumoku Extract, Yatsutama Tamoku Extract, Umitorano Extract, Oba Moku Extract, Fusis Mimoku Extract, Haha Moku Extract, Yoremok Extract, Sawtooth Moku Extract, Psyllium Moku Extract, Mukadenori Extract, Nuraxa Extract, Cronouraxa Extract, Oomkadenori Extract, Oomkadenori Extract Steller's root extract, Sponge extract, Fushitsunagi extract, Himefushitsunagi extract, Hirohafushitsugi extract, Black Zoekisu, Kobusozoekisu, Hanesozoekisu, Sozonohanaekisu, brush Saki sawtooth Hiba extract, Thira extract, duck over Tede bruises franc extract, Hamaikaekisu, port Leo Verde extract, Nabo Negro extract, Schisandra chinensis extract, Matsubusa extract, Binankazura extract, and the like.

(4) Melanin production promoter Specifically, salicylic acid or a salt thereof and derivatives thereof (salicylic acid glucoside, salicylic acid fatty acid ester, salicylic acid alcohol ether, salicylic acid amides, etc.), salicyl alcohol or a salt thereof and derivatives thereof, apigenin, Mentoflavone, Salamander extract, Udo extract, Shishido extract, Gash extract, Oak extract, Beetle extract, Cuckoo thistle extract, Gypsophila extract, Gymnema sylvestre extract, Carooo extract, Ginkgo biloba extract, Konronka extract, Sabon Ryokan extract, jasmine (pine licorice) extract, hollyhock extract, scallop extract, Arabidopsis thaliana extract, lily of the valley extract, Souuzu extract, deiko extract, eucommia (tonchu) extract, nagi Kada (Butcher Bloom) Extract, Teppouri Extract, Tokiwa Mansaku Extract, Nankin Gouze Extract, Elderflower Extract, Nadesico Extract, Michiyanagi Extract, Sardine Willow Extract, Morohaya Extract Zakifujime extract, Ryokakou extract, Ajigusa extract, Shellfish extract (cockle extract, green mussel extract, oyster extract, European oyster extract, scallop extract, clam extract, clam extract, snail extract, red mussel extract, red mussel extract, abalone extract, Sazae extract, bi-extract, etc.).

(5) Humectant Specifically, ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol , Polypropylene glycol, 1,3-butylene glycol, pentyl glycol, glycerin, erythritol, pentaerythritol, dipentaerythritol, threitol, arabitol, xylitol, ribitol, galactitol, sorbitol, mannitol, lactitol, maltitol, sicilitol, laminitol, Multivalent alcohols such as varienamin, validamin, and validatol Rubber, arabic gum, benzoin rubber, danmar gum, guaiac gum, Irish moss, Karaya gum, tragacanth gum, carob gum, quinseed, agar or its derivatives, casein, glucose, galactose, mannose, xylose, fructose, maltose, isomaltose, cellobiose , Gentiobiose, trehalose, cordobiose, laminaribiose, nigerose, cellobiose, sambubiose, neohesperidose, apiose, hammamellose, streptose, hydroxystreptose, dihydrostreptose, 2-methylerythrose or its derivatives, 2-methylerythronolactone , Mycarose, cladinose, accessone, alkanose, olivomai course, chromose, ebami course, vinero , Sugars such as nogarose, billenose, nobiose, moenuronic acid, galosamine, cybirosamine, N-acylcansamine, vancosamine, evanitrose, rubranitrose, tetronitrose, pyralose, α-octose, trioxacalcinose, aldgarose, blastmycin , Trehalose or its derivative, D-mannosamine and its derivative, isomaltoligosaccharide (panose), primeverose or its derivative, dextrin, gelatin, pectin, starch, carrageenan, carboxymethylchitin or chitosan, alkylene such as ethylene oxide (C2 to C4) ) Hydroxyalkyl (C2-C4) chitin or chitosan with added oxide, low molecular chitin or chitosan, chitosan salt, sulfated chitin or chitosan, phosphorus Chitin or chitosan, alginic acid or salt thereof, hyaluronic acid or salt thereof, chondroitin sulfate or salt thereof, 1,3-β-glucan, 1,4-β-glucan, 1,6-β-glucan, heparin, ethylcellulose, Methylcellulose, carboxymethylcellulose, carboxyethylcellulose, sodium carboxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, nitrocellulose, crystalline cellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylmethylether, polyvinylpyrrolidone, polyvinylmethacrylate, polyacrylate, polyethylene oxide And polyalkylene oxides such as polypropylene oxide or cross-linked polymers thereof, carboxyvinyl polymer, polyethyleneimine Water-soluble polymers such as dermatan sulfate and keratan sulfate, glycerin fatty acid pyrrolidone carboxylic acid esters, glycerin fatty acid acetyl amino acid esters, pyrrolidone carboxylic acid or salts thereof, polyaspartic acid or salts thereof, polyglutamic acid or salts thereof, polylysine Or a salt thereof, sodium lactate, hydantoin and derivatives thereof, Np-vinylbenzyl-D-cellobionamide, Np-vinylbenzyl-D-lactone amide, Np-vinylbenzyl-D-maltonamide, Np-vinylbenzyl-D- Gluconamide, glucosyloxyethyl methacrylate, galactosyloxypropyl acrylate, mannosyloxyethyl methacrylate, glutamyl lysine, glutaurine, 1,2,4-butanetriol, caran-3,4-diol, azoxaponin (3-o- [β- D-Glucopyranosyl- -D-glucuronopyranosyl] -sophoradiol, 3-o- [β-D-glucopyranosyl-3-D-glucuronopyranosyl] -soyasapogenol B, 3-o- [β-D-glucopyranosyl -β-D-glucuronopyranosyl] -azuxapogenol, 3-o- [β-D-glucopyranosyl] -28-o- [β-D-glucopyranosyl-β-D-glucopyranosyl] -dipsogenic acid, 3-o- [α-L-rhamnopyranosyl-β-D-glucopyranosyl-β-D-glucuronopyranosyl] -soyasapogenol B, 3-o- [β-D-glucopyranosyl-β-D-glu Chronopyranosyl] -29-o- [β-D-glucopyranosyl-β-D-glucopyranosyl] -azuxapogenol, etc.), Aoki (Aoki) extract, Aogiri extract, Kenashiaogiri extract (Akatsuki) extract, Red pepper Hemp) extract, red clover extract, Aki larch extract, Aguahe (Omiten palm) extract, Malva morning glory , Morning glory extract, athira (shokuyo kanna) extract, oilseed rape extract, amachazuru extract, amana (kojien) extract, ayuyu extract, hagatetou extract, higeigatou extract, garlic extract, cedar molygate extract, Hosoaogei Tou, Aogae Tou Extract, Haribiyu Extract, Aozulan Extract, Amaranthus Hypochondriax Extract, Aristolomeria (Urizuisen) Extract, Arcana (Arkana) Extract, Algarrobo (Cabbe) Extract, Aloe Vera Extract, Igusa (Light Heart Grass) Extract , Yew (first place) extract, strawberry extract, carob bean extract, Inazuna (teilexi) extract, rice extract, dog mint extract, iwa tobacco (Iwatsuki) extract, iwa hiba extract, iwa pine (roll mushroom) extract, wheat (chibu sanoki) extract, Chrysanthemum (Float) Extract, Usbenitachai Extract, Usvenia Oyster Extract, Unyadegato (Unkalia) Extract, Enokitake (Spider) Extract, Elingi Extract, Pre-Rotus Elingi Extract, Ogata Hawken Extract, Oguruma (Civil Scent) Extract, Steller's beetle (cereals) extract, oka extract, okazeli (serpentine) extract, okra extract, onidokoroko extract, tokoro extract, nagadokoroko (hikai) extract, onionis extract, yuuko extract, oyster extract, ginkgo biloba extract, gaku hydrangea Extract, Cascara Sagrada Extract, Gypsophila Extract, Panax Ginseng Extract, Kaniwa Extract, Carnation Extract, Gerbera Extract, Camcam (Duck) Extract, Color Extract, Oat Extract, Karin (Kiso) Extract, Kawara Psycho (White grass) extract, kawajisha extract, kawaranadeshiko (stone-bamboo) extract, ezokawara nadeshiko (buckwheat, buckwheat) extract, kantarasaasa extract, kikutanigiku extract, quinoa (quinoa) extract, cabbage extract, kiwi extract, cucumber extract, gyoryu (Nishikawa willow) , Taiyanagi) extract, Kiranso (golden grass weed) extract, guayule extract, Kusugikakazura (Tenmon winter) extract, Kudzu (Kazunori) extract, xanthus carp (yellow flower bud) extract, Kupuas extract, Gunba Nazuna (Sekimei, Sekimeishi) extract, Kemponashi (Kigushi) extract, gekkavidin (Beautiful Moon) extract, Koen (Hou Hou) extract, coconut extract, cosmos extract, coconut krill extract, rice oil extract, konjac extract, saffron (bancho flower, west red flower) extract, sapodilla extract, sangre Degrad (croton) extract, sa Cytin carrot (37 ginseng) extract, shea (carite) extract, cyanoki extract, shiitake extract (shiitake) extract, shimeji mushroom extract, hinoki shimeji mushroom extract, shaka shimeji mushroom extract, hatake shimeji mushroom extract, oscillating shimeji mushroom extract, beech shimeji mushroom extract, honji mushi extract, shirotamogitake extract, shimokure ( Pepper extract, Saishin extract, Cactus extract, Janohige (Bakumon winter) extract, Shukukonkamiso extract, Zozan hydrangea (Tsukuyama) extract, White crocodile extract, White-leafed azuki (chicken bone grass) extract, Ginkgo biloba (Ruika, Ruika flower) , Shencho Flower Extract, Watermelon Extract, Suzu-Psycho Extract, Suveruhiu (Horse Soap, Horse Toothpaste) Extract, Sekkok Extract, Sakura Sekkok Extract, Koki Sekkok Extract, Obanase Sekkok Extract, Okinawa Sekkok Extract, Hong Sea cucumber extract, ostrich coconut extract, deer wolfberry extract, kibanano pekkok extract, cedron extract, mallow extract, celery extract, senshinren extract (Hikai) extract, dahlia (tenjiku button) extract, tarwi extract, senkinshi extract, Japanese jujube extract, chankapiedora extract ) Extract, Tounabena (river cut) extract, corn extract, corn hair (southern cocoon) extract, Toxa (wood band) extract, ash (crust) extract, Turkish Kyary extract, jujube extract, vertical sword (tofu) extract, jujube (large) jujube) Kiss, Nabena (continuous) extract, Nameko extract, Namban karamashi (Hemp) extract, Niois violet extract, Nikuzuku extract, Nemunoki extract, Nebu extract, Nebi extract, Nemurinoki extract, Digokubana extract (Negai) extract, Nogateto extract, Hylandus extract, Houtiwa extract, Hachima bean extract, papaya extract, pahalobobo extract, balata gum extract, agaric extract, agaric bamboo extract, white mushroom extract, white-spotted mushroom extract, haran extract, pariurus (Prunus japonicus) extract, balsamina (Turureishi, bitter gourd) extract, Harlin Dou extract Hand Daikai extract, Higuruma dahlia extract, Beet extract, Hiba extract, Sunflower extract, Pepper extract, Himezu (Tempo) extract, Japanese apricot (Kawariharatake, (Romatsutake) extract, Fuyushinatsukusatake (Cycium Cordyceps) extract, Brazilian licorice extract, hazelnut extract, loofah extract, blossom extract (sparkling) extract, broom extract, elder extract, nendo, extract Horse-scented extract (Akansen, Acute pupa, Periosteus) extract, Futamata-kobe extract, Hosoba-kirinso (Keiten 37) extract, Jojoba extract, Borage extract, Bordeaux extract, Hononiku (meat jujube, Daiki) extract , Honsekoku (iron skin stone, sparrow mountain stone cocoon) extract, maca extract, macadamia nut extract, margaret (mokushungiku) extract, tamano sen haren extract, kyukonkinrenka extract, matatabi (wood tengu) extract, matsukasa extract, matsuhodo (茯苓) Extract, Matico (Cordonshi -Jo) extract, quince extract, malein (broad-mulled squid) extract, manzanya (Andesca mitselle) extract, psyllium extract, Japanese morning glory (Dragongrass) extract, green mint extract, wheat straw extract, munya extract, murasakikibu extract, purple pearl ) Extract, Murasaki Kinufu (Kunming chicken blood wisteria) extract, Moje (Pepper) extract, Ichigo extract, cornflower extract, Yacon extract, palm extract, Yabu tobacco (Tsuruga mushroom, Tenmeisei) extract, Maroni extract, Mokka extract, Lily extract , Ligan (Raimaru) extract, lime extract, rye extract, rakkyo extract, shallot (pepperum) extract, apple extract, gentian extract, litchi (piper, toothpick) extract, forsythia extract, yakuinin extract, mini sasanishiki extract Chlorella vulgaris extract, Chlorella pyrenoid extract, Chlorella ellipsoidia extract, Macrocystis pirifera extract, Yuikiri extract, Tosaka nori extract, Onyxa extract, Amakusa nori extract, Aomidro extract, Kawanori extract, Marimo extract, Motsuki hitoe extract, Ezoyahaz extract, Habanori extract, Atlantic havanori extract, Cotton bud extract, Sea bream extract, Trolo kombu extract, Antokume extract, Tsuruarame extract, Kuroshiome extract, Nekoa kombu extract, Ainu wakame extract, Chigaiso extract, Ezoi shige extract, Yabanemoku extract , Uganomok extract, Joromoku extract, Hiemoku extract, Tamanashimoku extract, Honda Walla extract, Sugimoku extract, Ushike Re-extract, Saubinori extract, Akebono mozuku extract, Cyprinus extract, Fusanori extract, Hoso-banamino-hana extract, Hanafno-ori extract, Itofonori extract, Kaginori extract, Mirin extract, Hoso-bamirin extract, Kikutosaka extract, Ezonameshi extract, Ibaranori extract, Key Ibaranori Extract, Saidaibara Extract, Tahibara Extract, Ogonori Extract, Crane Silamo Extract, Bee Crested Salamander Extract, Otsunori Extract, Red-backed Ginseng Extract, Natto Fungus Metabolites, Natto Extract Extract, Loofah Water, Birch (White Birch) or Akamatsu Sap etc. are mentioned.

(6) Cell activator / metabolic activator Specifically, vitamin A group: retinol or a salt thereof and derivatives thereof (retinyl unsaturation such as retinyl linoleate, retinyl linolenate, retinyl oleate, retinyl arachidonate, etc.) Fatty acid esters, etc.), retinal or salts thereof and derivatives thereof, dehydroretinal or salts thereof and derivatives thereof, retinoic acid or salts thereof and derivatives thereof, retinoic acid analogs (4-[[[8- (3,5 -Dimethylphenyl) -2-naphthalenyl] carbonyl] amino] benzoic acid, 4-[[[8- (3-methylphenyl) -2-naphthalenyl) carbonyl] amino] benzoic acid, 4-[[[8- (4 -Methylphenyl) -2-naphthalenyl] carbonyl] amino] benzoic acid, 4-[[[8- (2-methylphenyl) -2-naphthalenyl] carbonyl] amino] Benzoic acid, 4-[[[8- (3,4-dimethylphenyl) -2-naphthalenyl] carbonyl] amino] benzoic acid, 4-[[[8- (2,4-dimethylphenyl) -2-naphthalenyl ] Carbonyl] amino] benzoic acid, 4-[[[8- (2-isopropylphenyl) -2-naphthalenyl] carbonyl] amino] benzoic acid, 4-[[[8- (2-ethylphenyl) -2-naphthalenyl ] Carbonyl] amino] benzoic acid, 4-[[[8- (2-fluorophenyl) -2-naphthalenyl] carbonyl] amino] benzoic acid, 4-[[[8- (2-methoxyphenyl) -2-naphthalenyl ] Carbonyl] amino] benzoic acid, 4-[[(8-benzyl-2-naphthalenyl) carbonyl] amino] benzoic acid, 4-[(E) -2- (8-phenyl-2-naphthalenyl) propenyl] benzoic acid ), Retinoic acid derivatives (4-hydroxyphenylretinamide), retinoid analogs (4-[[(5,6-dihydro-5,5-dimethyl-8-ethyl-2-naphthalenyl) amino] carbonyl] benzoic acid, 4-[[((5,6-dihydro-5,5,8- Trimethyl-2-naphthalenyl) amino] carbonyl] benzoic acid, 4-[[(5,6-dihydro-5,5-dimethyl-8-phenyl-2-naphthalenyl) amino] carbonyl] benzoic acid, 4-[[( 5,6-dihydro-5,5-dimethyl-8-ethyl-2-naphthalenyl) carbonyl] amino] benzoic acid, 4-[[((5,6-dihydro-5,5,8-trimethyl-2-naphthalenyl) -Carbonyl] amino] benzoic acid, 4- (E)-[2- (5,6-dihydro-5,5-dimethyl-8-phenyl-2-naphthalenyl) -1-propenyl] benzoic acid, 4-[[ (5,6-dihydro-5,5-dimethyl-8-phenyl-2-naphthalenyl) oxy] carbonyl] benzoic acid, 4-[[((5,6-dihydro-5,5-dimethyl-8-phenyl-2) -(Naphthalenyl) carbonyl] amino] repose Acid, 4-[[(5,6-dihydro-5,5-dimethyl-8-phenyl-2- (naphthalenyl) carbonyl] oxy] benzoic acid, 4-[[5,6-dihydro-5,5-dimethyl -8- (2-Fluorophenyl) -naphthalenyl] carbonyl] amino] benzoic acid, 4-[[(5,6-dihydro-5,5,6-trimethyl] -8-phenyl-2- (naphthalenyl) carbonyl] Amino] benzoic acid, 4-[[((5,6-dihydro-5,5,7-trimethyl-8-phenyl-2-naphthalenyl) carbonyl) benzoic acid, 4-[[(E)-(5,6- Dihydro-5,5-dimethyl-8-phenyl) -2-naphthalenyl] vinyl] benzoic acid, 4-[[[((5,6-dihydro-5,5-dimethyl-8-phenyl) -2-naphthalenyl] carbonyl ] Sulfamil] benzoic acid, 4-[[[(5,6-dihydro-5,5-dimethyl-8-phenyl-2-naphthalenyl] sulfamyl] carbonyl] benzoic acid, 4-[[(5,6-dihydro- 5,5-Dimethyl-8-fe Nyl) -2-naphthalenyl] ethyl] benzoic acid, 4-[[[((5,6-dihydro-5,5-dimethyl-8-phenyl) -2-naphthalenyl] thiocarbonyl] amino] benzoic acid, 4- [ [[(5,6-dihydro-5,5-dimethyl-8-phenyl) -2-naphthalenyl] carbonyl] methyl] benzoic acid, 4-[[[((5,6-dihydro-5,5-dimethyl-8 -Phenyl) -2-naphthalenyl] methyl] oxy] benzoic acid, 4-[[[((5,6-dihydro-5,5-dimethyl-8-phenyl) -2-naphthenyl] oxy] methyl] benzoic acid, 4 -[[[((5,6-dihydro-5,5-dimethyl-8- (2,4-dimethylphenyl)]-2-naphthalenyl] carbonyl] amino] benzoic acid, 4-[[[((5,6- Dihydro-5,5-dimethyl-8- (4-methylphenyl)]-2-naphthalenyl] carbonyl] amino] benzoic acid, 4-[[(5,6-dihydro-5,5-dimethyl-8-phenyl) -2-Naphthalenyl] ethyl] repose Acid 4-[[[(5,6-dihydro-5,5-dimethyl-8-phenyl) -2-naphthalenyl] sulfamyl] methyl] benzoic acid, 4-[[(5,6-dihydro-5,5 -Dimethyl-8-phenyl) -2-naphthalenyl] methyl] amino] benzoic acid, 4-[[[((5,6-dihydro-5,5-dimethyl-8-phenyl) -2-naphthalenyl] amino] thiocarbonyl ] Benzoic acid, 4-[[[((5,6-dihydro-5,5-dimethyl-8-phenyl) -2-naphthalenyl] methyl] sulfamyl] benzoic acid, 4-[[[((5,6-dihydro- 5,5-dimethyl-8-phenyl-2-naphthalenyl] amino] methyl] benzoic acid, 4-[[[[(5,6-dihydro-5,5-dimethyl-8-phenyl) -2-naphthalenyl] carbonyl] Amino] -2-hydroxybenzoic acid, 4-[[[((5,6-dihydro-5,5-dimethyl-8-phenyl) -2-naphthalenyl] carbonyl] amino] -2-nitrobenzoic acid, 4- [ [[(5,6-dihydro- 5,5-dimethyl-8-phenyl) -2-naphthalenyl] carbonyl] amino] -2-fluorobenzoic acid, 4-[[[((5,6-dihydro-5,5-dimethyl-8-phenyl-2-) Naphthalenyl] carbonyl] amino] -2-methoxybenzoic acid, 4-[[[((5,6-dihydro-5,5-dimethyl-8- (2-naphthalene)]-2-naphthalenyl] carbonyl] amino] benzoic acid 4-[[(5,6-dihydro-8-phenyl-2-naphthalenyl) carbonyl] aminobenzoic acid, 4-[[(5,6-dihydro-5,5-dimethyl-8-phenyl-2-naphthalenyl ) Carbonyl] amino] -3-fluorobenzoic acid, 4-[[((5,6-dihydro-5,5-dimethyl-8-phenyl-2-naphthalenyl) carbonyl] amino] -3-methylbenzoic acid, 4- [[(5,8,10,10a-Tetrahydro-10,10-dimethyl-9-phenyl-2-anthracenyl) carbonyl] amino] benzoic acid, 4-[[(1,1-dimethyl-3-phenyl-1H1 -In -5-yl) amino] carbonyl] benzoic acid, 4-[(1,1-dimethyl-3-phenyl-1H-inden-5-yl-oxymethyl) benzoic acid, 4- [2- (1,1 -Dimethyl-3-phenyl-1H-inden-5-yl) vinyl] benzoic acid, 4-[(1,1-dimethyl-3-phenyl-1H-indene-5-carbonyl) amino] benzoic acid), carotene or Salts thereof and derivatives thereof (α-carotene, β-carotene, γ-carotene, lycopene, cryptoxanthine, lutein, zeaxanthin, isozeaxanthin, rhodoxanthine, capsanthin, crocetin and other carotenoids), lycopene or a salt thereof and derivatives thereof, vitamin B Group: Thiamine or salts thereof and derivatives thereof (thiamine hydrochloride, thiamine disulfide, bisbenchamine, bisbutiamine, thiamine monophosphate disulfide, benf Thiamine, chicotiamine, octothiamine, dicetiamine, fursultiamine, prosultiamine, astaxanthinthiamine phosphate diester, etc.), thiamine sulfate, riboflavin or its salts and derivatives thereof (flavin adenine dinucleotide, flavin mononucleotide, riboflavin phosphate) Diester, 1-β-D-ribofuranosyl nicotinamide pyrophosphate diester, 1-β-D-ribofuranosyl nicotinic acid, etc.), pyridoxine or a salt thereof and derivatives thereof (pyridoxine 3,4-dipalmitate, 3 , 4-dicaprylic acid pyridoxine, pyridoxine sulfate diester, etc.), pyridoxal or a salt thereof and derivatives thereof, pyridoxamine or a salt thereof and derivatives thereof, cyanocobalamin or a salt thereof and derivatives thereof, cobalamins (me Lucobalamin, adenosylcobalamin, hydroxocobalamin, aquacobalamin, etc.), folic acid or a salt thereof and derivatives thereof, nicotinic acid or a salt thereof and derivatives thereof, pantothenic acid or a salt thereof and derivatives thereof, biotin or a salt thereof and their Derivatives, choline or salts thereof and derivatives thereof, inositol or salts thereof and derivatives thereof, vitamin C group: ascorbic acid or salts thereof and derivatives thereof, vitamin D group: ergocalciferol or salts thereof and derivatives thereof, Calciferol and its salts and their derivatives (1α-hydroxy-22-[(1-hydroxy-1-methyl) -2-cyclopenten-4-yl-oxy] -23,24,25,26,27-pentanol Cholecalciferol, [1R, 4R] -1α-hydroxy-22-[(1-hydroxy-1-methyl -2-Cyclopenten-4-yl-oxy] -23,24,25,26,27-pentanorolecalciferol, [1R, 4S] -1α-hydroxy-22-[(1-hydroxy-1-methyl) -2-Cyclopenten-4-yl-oxy] -23,24,25,26,27-pentanorolecalciferol, [1S, 4R] -1α-hydroxy-22-[(1-hydroxy-1-methyl) -2-Cyclopenten-4-yl-oxy] -23,24,25,26,27-pentanorolecalciferol, [1S, 4S] -1α-hydroxy-22-[(1-hydroxy-1-methyl) -2-cyclopenten-4-yl-oxy] -23,24,25,26,27-pentanorolecalciferol, etc.), dihydrotaxosterol or a salt thereof and derivatives thereof, vitamin E group: tocopherol or a salt thereof, and Derivatives thereof, tocotrienol or a salt thereof and derivatives thereof, ubiquinone or a salt thereof and derivatives thereof, vitamin K group: phyto Dione or a salt thereof and derivatives thereof, menaquinone or a salt thereof and derivatives thereof, menadione or a salt thereof and derivatives thereof, menadiol or a salt thereof and derivatives thereof, vitamin F group: linoleic acid or a salt thereof and derivatives thereof, Linolenic acid or a salt thereof and derivatives thereof, arachidonic acid or a salt thereof and derivatives thereof, carnitine or a salt thereof and derivatives thereof, ferulic acid or a salt thereof and derivatives thereof, γ-oryzanol or a salt thereof and derivatives thereof Orotic acid or a salt thereof and derivatives thereof, vitamin P group: rutin or a salt thereof and derivatives thereof, eriocitrin or a salt thereof and derivatives thereof, hesperidin or a salt thereof and derivatives thereof, vitamin L group: anthranilic acid or Its salty And derivatives thereof, adenylthiomethylpentose or a salt thereof and derivatives thereof, vitamin U group: methylmethionine sulfonium chloride or a derivative thereof, valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, Asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, histidine or a derivative thereof (N-octyloxycarbonyl-β-alanyl-L-histidine, N- Dodecyloxycarbonyl-β-alanyl-L-histidine, N- (12-amino-1-oxododecyl) -L-histidine, N-2-ethylhexyloxycarbonyl-β-alanyl-L-histidine hydrochloride, N-he Sadecyloxycarbonyl-β-alanyl-L-histidine, N-octylaminocarbonyl-β-alanyl-L-histidine, N-dodecylaminocarbonyl-β-alanyl-L-histidine, N-dodecylsulfonyl-β-alanyl- L-histidine, N-dodecylamino-oxalyl-β-alanyl-L-histidine, etc.) and their amino acids such as sulfates, phosphates, nitrates, citrates, and amino acid derivatives such as pyrrolidone carboxylic acid Α-hydroxy acids such as glycolic acid, citric acid, malic acid, tartaric acid, lactic acid, succinic acid, 2-hydroxycarboxylic acids (methyl lactic acid, 2-hydroxybutanoic acid, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, 2-hydroxyheptanoic acid, 2-hydroxyoctanoic acid, 2-hydroxynonanoic acid, 2-hydroxydecanoic acid, 2-hydroxyundecanoic acid, α-hydro Xylauric acid, α-hydroxymyristic acid, α-hydroxypalmitic acid, α-hydroxystearic acid, α-hydroxyarachidonic acid, cerebronic acid, α-hydroxynervonic acid, mandelic acid, benzylic acid, phenyllactic acid, atrolactic acid, 2- (4′-hydroxyphenyl) -2-hydroxyethanoic acid, 2- (4′-chlorophenyl) -2-hydroxyethanoic acid, 2- (3′-hydroxy-4′-methoxyphenyl) -2-hydroxyethanoic acid, 2- (4'-hydroxy-3'-methoxyphenyl) -2-hydroxyethanoic acid, 3- (2'-hydroxyphenyl) -2-hydroxypropanoic acid, 3- (4'-hydroxyphenyl) -2-hydroxy Propanoic acid, 2- (3 ', 4'-dihydroxyphenyl) -2-hydroxyethanoic acid, glyceric acid, erythronic acid, ribbon acid, arabinonic acid, xylonic acid, lyxonic acid, aronic acid, altronic acid, g Luconic acid, mannonic acid, gulonic acid, idonic acid, galactonic acid, talonic acid, glucoheptonic acid, galactoheptonic acid, tartronic acid, mucinic acid, etc.), polyhydroxycarboxylic acid or hydroxypolycarboxylic acids (gluconolactone, galactonolactone, Glucuronolactone, galacturonolactone, gulonolactone, ribonolactone, sugar acid lactone, pantoyl lactone, glucoheptonolactone, mannonolactone, galactoheptonolactone, etc.), 2-keto acids (glyoxylic acid, methyl 2-ketoethanoate) Benzoylformic acid, methyl benzoylformate, ethyl benzoylformate, phenylpyruvic acid, methyl phenylpyruvate, ethyl phenylpyruvate, 2-ketobutanoic acid, 2-ketopentanoic acid, 2-ketohexanoic acid, 2-ketoheptanoic acid, 2-ketooctaoctane Acid, 2-ketododecanoic acid, methyl 2-ketooctanoate, etc.), quinic acid, isocitric acid, tropic acid, tretocanic acid, 3-chlorolactic acid, cerebronic acid, citramalic acid, agaricinic acid, alolithic acid, pantoic acid, lactobionic acid, Hexulosonic acid, photosensitizer 301, hinokitiol, pantothenic acid or derivative thereof, allantoin, pentadecanoic acid glyceride, linolenic acid or derivative thereof, eicosapentaenoic acid or derivative thereof, docosahexaenoic acid or derivative thereof, estradiol, etenyl estradiol, antiallol or Its glycoside, Liononiresinol or its glycoside, Rhodendendrol or its glycoside, Platyphyronol or its glycoside, Lactone compound (D-glucurono-6,3-lactone, α-D-glucoheptonic -γ-lactone, δ-gluc Lonolactone, α, β-glucooctonic-γ-lactone, L-glonic-γ-lactone, γ-D-galactonolactone, D-saccharide-1,4-lactone, D-saccharide-3,6-lactone, D-ribonic-γ-lactone, α-butyrolactone, γ-butyrolactone, α-octanoic lactone, γ-octanoic lactone, nonanoic lactone, γ-valerolactone, D-manninoic-δ-lactone, D-xyleuric -δ-lactone, D-arabinoic-δ-lactone, stearoyl-δ-gluconolactone, DL-pantolactone, palmitoyl-DL-pantolactone, etc.), 3-hydroxy-3,4-dicarboxy-1,4- Butanolide or its derivative, 6-benzylaminopurine or its derivative, 1,4-diazadicyclooctane, 2,5-dimethylfuran, 2-methylfuran, 2,5-diphenylfuran, 1,3-diphenylisobenzo Orchid, rutin, tektrigenin 7-xylosyl glucoside, captopril, alacepril, lisinopril, enalapril, delapril, benazepril, cilazapril, imidapril, quinapril, trandelapril, perindopril, temocapril, losartan, endothelin, galactomannin trimethyl polymer Glycine, proteoglycan, lactic acid bacteria extract, lactic acid bacteria culture extract, lactic acid bacteria fermented milk extract, bifidobacteria extract, bifidobacteria culture broth extract, bifidobacteria fermented milk extract, placenta extract, ganoderma extract, spleen extract, thymus extract, yeast extract, yeast Culture fluid extract, yeast fermentation extract, filamentous fungus extract, filamentous fungus culture fluid extract, basidiomycete extract, basidiomycete culture fluid extract, bacterial cell disruption extract, bacterial culture fluid extract, culture Human dermal cell disruption extract, red ginger extract, fennel extract, barley extract, barley extract, oakuri higotai (Yeoju leakage, indigo piercing) extract, corn fly Extract, Hypericum perforatum extract, Dutch jellied extract, Dutch honey beet extract, Silkworm extract, Roman chamomile extract, Garcinia extract, Kawarani carrot (blue agate) extract, Kakiran extract, Quillaja extract, Kinlan extract, Ginkgo biloba extract, Calendula extract, Sakaneran (Ezosacaneran) ) Extract, Sababagin orchid extract, Sawagurumi (Yamatomo) extract, Shimotsuke extract, Shajin extract, Sumomo extract, Japanese walnut extract, Japanese horsetail extract, pineapple extract, Chinese squirrel extract , Beech extract, physalis (Torone) extract, maitake (maiko) extract, misohagi (senju-na) extract, mukuge (kiso) extract, mukuroji (longevity skin) extract, bean sprout, eucalyptus extract, yukinoshita (tiger ear grass) ) Extract, Suabisimus extract, Lettuce extract, Aloe extract, Ogon extract, Tonka bean extract, Gentianana extract, Burdock extract, Shikon extract, Carrot extract, Hamamelis extract, Hop extract, Yokuinin extract, Odrichos extract, Assembly Extract, Toki Extract, Toki-Senka Extract, Achacha Extract, Hypericum Extract, Cucumber Extract, Papaver Extract, Rosemary Extract, Parsley Extract, Sanadagusa Extract, Fukurin Amiji Extract, Gobble Comb Extract, Oyster Comb Extract, Onikobue Examples include kiss, gohei comb extract, nagacombu extract, pea comb extract, large dwarf extract, rattle extract, flatfish extract, benimozuku extract, hosobenimozuku extract, kagekinori extract, ezotosaka extract, silamo extract, birch extract and the like.

(7) Antioxidants Specifically, ascorbic acid or a salt thereof and derivatives thereof (phosphoric acid-magnesium ascorbate, ascorbyl palmitate, ascorbyl dipalmitate, ascorbyl hydroxyprophosphate, 5- o-α-D-Glucopyranosyl-L-ascorbic acid, L-ascorbic acid phosphate sodium salt, L-ascorbic acid phosphate potassium salt, L-ascorbic acid phosphate magnesium salt, L-ascorbic acid phosphate Calcium salt, L-ascorbic acid phosphate aluminum salt, L-ascorbic acid sulfate sodium salt, L-ascorbic acid sulfate potassium salt, L-ascorbic acid sulfate magnesium salt, L-ascorbic acid sulfate calcium salt, L -Ascorbic acid sulfate aluminum Nium salt, L-ascorbic acid sodium salt, L-ascorbic acid potassium salt, L-ascorbic acid magnesium salt, L-ascorbic acid calcium salt, L-ascorbic acid aluminum salt, 6-o-α-D-galactopyranosyl -L-ascorbic acid, 2-o-β-D-galactopyranosyl-L-ascorbic acid, L-ascorbic acid phosphate magnesium salt, L-ascorbic acid phosphate sodium salt, L-ascorbic acid sulfate Sodium salt, 6-o-acyl ascorbic acid phosphate sodium salt, 6-o-acyl ascorbic acid phosphate ammonium salt, 6-o-acyl ascorbic acid phosphate isopropanolamine salt, 3-o-isopropyl-L -Ascorbic acid, 6-o-alkylascorbic acid potassium phosphate, 6-o-alkylascorbic acid phosphate calcium Um salt, 6-o-alkyl ascorbic acid phosphate barium salt, 6-o-alkyl ascorbic acid phosphate ammonium salt, 6-o-alkyl ascorbic acid phosphate monoethanolamine salt, 6-o-alkyl ascorbine Acid phosphate ester diethanolamine salt, 6-o-alkylascorbic acid phosphate triethanolamine salt, 6-o-alkylascorbic acid phosphate monoisopropanolamine salt, 6-o-alkylascorbic acid phosphate diisopropanolamine Salt, 6-o-alkylascorbic acid phosphate triisopropanolamine salt, 3-o-glycosyl-L-ascorbic acid, 6-o-β-D-galactopyranosyl-L-ascorbic acid, ascorbic acid phosphate Cholesterol ester, L-ascorbyl palmitate, L-isopalmitate Scorbyl, L-ascorbyl dipalmitate, L-ascorbyl diisopalmitate, L-ascorbyl stearate, L-ascorbyl isostearate, L-ascorbyl distearate, L-ascorbyl diisostearate, L-ascorbyl myristate, isomyristate L-ascorbyl, dimyristic acid L-ascorbyl, diisomyristic acid L-ascorbyl, 2-ethylhexanoic acid L-ascorbyl, di-2-ethylhexanoic acid L-ascorbyl, oleic acid L-ascorbic acid, 2-o-α -D-glucosyl-L-ascorbic acid, 2-o-α-D-maltosyl-L-ascorbic acid, 2-o-α-D-maltotriosyl-L-ascorbic acid, 3-o-α-D- Glucosyl-L-ascorbic acid, 2-o-α-D-maltosyl-L-ascorbic acid, 2-o-α-D-maltotriosyl-L-ascorbic acid, L-ascorbic acid tetraisopalmitin Ester, L-Ascorbic acid tetralauric acid ester, L-Ascorbic acid tetra-2-ethylhexanoic acid ester, L-Ascorbic acid tetraoleic acid ester, 5,6-isopropylidene-L-ascorbic acid, Lu, L-ascorbine Acid retinol ester, L-ascorbic acid-DL-tocopherol phosphate ester, L-3-o-ethylascorbic acid, L-ascorbic acid tristearate, L-ascorbic acid tripalmitate, L-ascorbic acid trioleate, L -Ascorbyl triphosphate, 2-o-ascorbyl cinnamate, 2-o-ascorbyl ferrate, 2-o-ascorbyl caffeate, 2-o-ascorbyl synapate, 2-o- [6-palmitoyl ascorbyl]- 4'-acetoxyferrate, DL-α-tocopherol-2-L-ascorbic acid diester, ascorbic acid Cytol-binding derivatives, ascorbic acid phosphoramide derivatives, ascorbic acid arbutin conjugates, ascorbyl phosphoryl cholesterol, chromanyl ascorbic acid derivatives, ascorbic acid sialic acid derivatives, etc.), stearates, tocopherols or salts thereof and derivatives thereof (α-tocopherol, β -Tocopherol, γ-tocopherol, δ-tocopherol, ε-tocopherol, α-tocopheryl retinoate, aminomethylated tocopherol, hydroxymethylated tocopherol, tocopheryl phosphate, tocopherol acetate, tocopherol nicotinate, tocopherol succinate, tocopherol Linoleate, tocopherol orotate, DL-α-tocopheryl glucoside, DL-α-tocopheryl maltoside, DL-β-tokov Lyl glucoside, DL-β-tocopheryl maltoside, DL-γ-tocopheryl glucoside, DL-γ-tocopheryl maltoside, DL-δ-tocopheryl glucoside, DL-δ-tocopheryl maltoside, D-α- Tocopheryl glucoside, D-α-tocopheryl maltoside, D-β-tocopheryl glucoside, D-β-tocopheryl maltoside, D-γ-tocopheryl glucoside, D-γ-tocopheryl maltoside, D-δ -Tocopheryl glucoside, D-δ-tocopheryl maltoside, L-α-tocopheryl glucoside, L-α-tocopheryl maltoside, L-β-tocopheryl glucoside, L-β-tocopheryl maltoside, L- γ-tocopheryl glucoside, L-γ-tocopheryl maltoside, L-δ-tocopheryl glucoside, L-δ-tocopheryl maltoside, 1- (sulfoethylamino) -3- (α-tocopheryl-6 -Iroxy) propan-2-ol 1- (carboxypropylamino) -3- (α-tocopheryl-6-iroxy) propan-2-ol hydrochloride, S- [3- (α-tocopheryl-6-iroxy) -2-hydroxypropyl ] Cysteine, S- [3- (α-Tocopheryl-6-iroxy) -2-hydroxypropyl] -γ-glutamylcystenylglycine, N- [3- (α-tocopheryl-6-iroxy)- 2-hydroxypropyl] aspartic acid, N- [3- (α-tocopheryl-6-yloxy) -2-hydroxypropyl] glutamic acid, etc.), tocotrienol or a salt thereof and derivatives thereof (α-tocotrienol, β-tocotrienol) , Γ-tocotrienol, δ-tocotrienol, tocotrienol acetate, tocotrienol nicotinate, tocotrienol succinate, tocotrienol linoleate, tocotrienol orote Dihydropyridine derivatives (methyl-3-phenyl-2-propenyl 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) pyridine-3,5-dicarboxylate and its salts), Benzochroman derivatives, nordihydrogua ceretenoic acid, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), hydroxytyrosol, parahydroxyanisole, propyl gallate, sesamol, sesamolin, gossypol, maritimaine, sulfretin, xanthene-2, 7-diols, caffeoylquinic acids, propolis, carotenoids (α-carotene, β-carotene, γ-carotene, lycopene, lutein, violaxanthin, spiroloxanthine, spheroidene, astaxanthin, etc.), phlorotannins, akebi (wood) Tsu) extract, amacha (sweet tea) extract, oolong Extract, Dutch beetle extract, kanran extract, kumquat extract, gobishi extract, geno shochu (old lady's grass) extract, sesame extract, sesame cultured cell extract, sesame extract, rice bran extract, pomegranate extract, salamander extract, pear Extract, Daio extract, Tomato extract, Nanten extract, Noisami extract, Neubara extract, paprika extract, pistachio extract, loquat extract, betel wax extract Buffalo extract, Bokeh extract, Hosobaoguruma extract, Mao (mao) extract, Mimosa extract, Mebogi extract, Himekuma willow extract, Yanagita extract, Watafujitsugi (Mitsumonflower) extract, Chlamydomonas extract, Red-bellied extract, Kona michuiwa extract, Akaba Miuchiwa Kiss, St. John's wort extract, witch hazel extract, clove extract, Melissa extract, EMME picolinimidate extract, white birch extract, salvia extract, rosemary extract, nandina fruit extract, ginkgo extract, green tea extract, clove extract, and the like.

(8) Reactive oxygen scavenger / radical scavenger Specifically, superoxide dismutase, catalase, glutathione peroxidase, bilirubin, quercetin, quercitrin, catechin, catechin derivatives, rutin or derivatives thereof, gallic acid or salts thereof, and their Derivatives, curcumin or salts thereof and derivatives thereof, transferrin, ceruloplasmin, coenzyme Qn (n = 7 to 10), uric acid, bilirubin, metallothionein, stilbengaloyl glycoside (3,5,4′-trihydroxystilbene 4 '-o-β-D- (6 "galloyl) glucopyranoside, 3,5,4'-trihydroxystilbene 4'-o-β-D- (2" galloyl) glucopyranoside, etc.), chlorogenic acid phospholipid ester, chlorogen Acid sphingosine ester and derivatives thereof, chlorogenic acid glycolipid ester, Acid sugar ester, chlorogenic acid sterol ester, thiazole derivative or salt thereof (2- (3,4-diethoxyphenyl) -4- (3-carboxy-4-hydroxyphenyl) thiazole, 2- (3,4-di) Ethoxyphenyl) -4- [3-carboxy-4-hydroxy-5- (2-methyl-2-propenyl) phenyl] thiazole and 2- (3,4-diethoxyphenyl) -4- (3-carboxy-4 -Hydroxy-5-methylphenyl) thiazole, 2- (3,4-diethoxyphenyl) -4- (3-carboxy-5-methoxyphenyl) thiazole,), hydroxymatylesinol, allohydroxymatylesinol, hydantoin Derivatives, Akaminoki (logwood) extract, Akamegasiwa (Akabudi) extract, Akamino Akane extract, Akane akane extract, Akane (Root) extract, Hydrangea (hydrangea) extract, Abemaki extract, Fig , Ginkgo biloba extract, Asparagus extract, Plum (Plum) extract, Vulgaris extract, Prunus quercivorus extract, Estragon extract, Enju (Scarlet flower, Satsuma rice) extract, Kashiwa (Salmon tree, coconut leaf) extract , Genus extract, birch extract, birch extract, cucumber extract Extract, Sasa (Amber) Extract, Perilla Extract, Ajizo Extract, Chimmen Diso Extract, Catamen Diso Extract, Peonies (Gakuen) Extract, Quercus Extract, Japanese Quail Extract, Crape Myrtle Extract, Zicopi Extract, Shirakashi Extract, White Clover (Clover) Extract, Horseradish D , Black tea extract, green tea extract, camellia tea extract, tencha (tea) extract, tender eel extract, naniwai rose (gold cherry) extract, peanut (peanut) extract, kei extract, nikkei extract, ceylon nicky extract, yabuni kei (cinnamon) extract, keishi ( (Keishi branch) extract, Nozenkazura (Ryokan flower) extract, lotus (lotus) extract, Chinese cabbage extract, hadakamugi extract, Hanasuge (my mother) extract, Hermanus (maikai flower) extract, rose (rose) extract, barbasco extract, spinach extract, Beech extract, American beech extract, Inu beech extract, European beech extract, Convolvulus extract, Hosobana okera (蒼朮) extract, Button (peony) extract, Mayoram (Annelida) extract, Melon extract, Oenothera extract, Snowy willow extract, Orchid extract, Lacanca extract, Louis Suekisu, Naminohanaekisu, Yukari extract, bombardier Yukari extract, Azusaekisu, basil extract, woodworking (climate) extract, Hime Fuuro extract, lemon grass extract, and the like.

(9) Fat metabolism promoter Specifically, phthalazine derivatives (4-ethyl-1- (β-hydroxyethylamino) phthalazine, 4-N-propyl-1- (β-hydroxyethylamino) phthalazine, 4-N -Butyl-1- (β-hydroxyethylamino) phthalazine, 4-N-butyl-1- (β-hydroxypropylamino) phthalazine, etc.), xanthine derivatives (caffeine, theophylline, theobromine, xanthine, aminophylline, choline theophylline, Diprofylline, proxyphylline and oxtriphyrin, etc.), Aotsuki-rafuji (wooden cocoon) extract, thistle extract, ale thistle extract, mallow thistle extract, scrub thistle extract, noel thistle extract, abalone thistle extract, cacao extract, elcampuri extract, giant crab raft (Prevention) Extract, Gajutsu (Amber) Extract, Carax Salmon Man Extract Pepper extract ) Extract, cinnamon extract, primrose extract, red ginseng extract, ginseng extract (dragon gall) extract, naginata kouju extract, banana extract, puerh tea (pure tea) extract, plum extract, boufu (windproof) extract and the like.

(10) UV protective agent / UV absorption accelerator Specifically, benzophenone derivatives (2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 2-hydroxy-4-methoxybenzophenone) -5-sulfonate sodium, dihydroxydimethoxybenzophenone, dihydroxydimethoxybenzophenone-sodium sulfonate, 2,4-dihydroxybenzophenone, tetrahydroxybenzophenone, etc.), 1,2-dihydroxy-4- (2-hydroxyethyl) benzene derivatives (1 -(2- (4- (3,4-dihydroxycinnamoyl) -3-rhamnosyl) glucosyl) ethyl-3-hydroxy-4-methoxybenzene, 1- (2- (6- (3,4-dihydroxycinnamoyl) ) -3-Rhamnosyl) glucosyl) ethyl-3-hydroxy-4-methoxybenzene, 1- (2- (2-acetyl-4- (3,4-dihy)) Loxicinnamoyl) -3-rhamnosyl) glucosyl) ethyl-3,4-dihydroxybenzene, 1- (2- (2-acetyl-6- (3,4-dihydroxycinnamoyl) -3-rhamnosyl) glucosyl) ethyl- 3,4-dihydroxybenzene, 1- (2- (4- (3,4-dihydroxycinnamoyl) -3-rhamnosyl) glucosyl) ethyl-3,4-dihydroxybenzene, 1- (2- (6- (4 -Hydroxy-3-methoxycinnamoyl) -3-rhamnosyl) glucosyl) ethyl-3,4-dihydroxybenzene, 1- (2- (4- (3,4-dihydroxycinnamoyl) -3-rhamnosyl) glucosyl)- 1-methoxyethyl-3,4-dihydroxybenzene, 1- (2- (4- (3,4-dihydroxycinnamoyl) -3-rhamnosyl) glucosyl) -1-hydroxyethyl-3,4-dihydroxybenzene, 1 -(2- (6- (3,4-dihydroxycinnamoyl) -3-xylosyl) glucosyl) Ru-3,4-dihydroxybenzene, 1- (2- (3-allosyl-6- (3-hydroxy-4-methoxycinnamoyl)) glucosyl) ethyl-3,4-dihydroxybenzene, 1- (2- ( 3-glucosyl-6- (3-hydroxy-4-methoxycinnamoyl)) glucosyl) ethyl-3-hydroxy-4-methoxybenzene, 1- (2- (3-arosyl-6- (3-hydroxy-4-) Methoxycinnamoyl) glucosyl) ethyl-3-hydroxy-4-methoxybenzene, 1- (2- (4- (3,4-dihydroxycinnamoyl) glucosyl) ethyl) -3,4-dihydroxybenzene, 1- (2 -(3- (3,4-dihydroxycinnamoyl) glucosyl) ethyl) -3,4-dihydroxybenzene, 1- (2- (2- (3,4-dihydroxycinnamoyl) glucosyl) ethyl) -3,4 -Dihydroxybenzene, 1- (2- (6- (3,4-dihydroxycinnamoyl) glucosyl) ethyl) -3,4-dihydride Roxybenzene, etc.), paraaminobenzoic acid derivatives (paraaminobenzoic acid, ethyl paraaminobenzoate, glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate, octyl paradimethylaminobenzoate, etc.), methoxycinnamate derivatives (ethyl paramethoxycinnamate, Isopropyl paramethoxycinnamate, octyl paramethoxycinnamate, 2-ethoxyethyl paramethoxycinnamate, sodium paramethoxycinnamate, potassium paramethoxycinnamate, di-2-methoxycinnamate mono-2-ethylhexanoate glyceryl, etc.), anthranilic acid derivatives (such as methyl anthranilate) ), Urocanic acid derivatives (urocanic acid, ethyl urocanate, etc.), coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyriline Gin derivatives, dioxane derivatives, camphor derivatives, furan derivatives, pyrone derivatives, nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, pyridoxine derivatives, pyridoxal derivatives, pyridoxamine derivatives, amethoflavone, neosacranin, 6-dehydrocaine, triazine derivatives (4,4 '4 "-(1,3,5-triazine-2,4,6-triyltriimino) trisbenzoic acid tris-2-ethylhexyl etc.), phosphatidyl chromanol derivatives (1,2-dilaurolylglycero-3- Phospho-2'-hydroxymethyl-2 ', 5', 7 ', 8'-tetramethyl-6'-hydroxychroman, 1,2-dimyristoylglycero-3-phospho-2'-hydroxymethyl-2', 5 ', 7', 8'-tetramethyl-6'-hydroxychroman, 1,2-dipalmitoylglycero-3-phospho-2'-hydroxymethyl-2 ', 5', 7 ', 8'-tetramethyl -6'-hydroxychroman, 1,2 -Distearoyl glycero-3-phospho-2'-hydroxymethyl-2 ', 5', 7 ', 8'-tetramethyl-6'-hydroxychroman, 1,2-dialachidonyl glycero-3-phospho-2 '-Hydroxymethyl-2', 5 ', 7', 8'-tetramethyl-6'-hydroxychroman, 1-myristoyl-2-palmitoylglycero-3-phospho-2'-hydroxymethyl-2 ', 5' , 7 ', 8'-Tetramethyl-6'-hydroxychroman, 1-myristoyl-2-stearoylglycero-3-phospho-2'-hydroxymethyl-2', 5 ', 7', 8'-tetramethyl- 6'-hydroxychroman, 1-palmitoyl-2-myristoylglycero-3-phospho-2'-hydroxymethyl-2 ', 5', 7 ', 8'-tetramethyl-6'-hydroxychroman, 1-palmitoyl- 2-stearoylglycero-3-phospho-2'-hydroxymethyl-2 ', 5', 7 ', 8'-tetramethyl-6'-hydroxychroman, 1-stearoyl-2-myristoylglycero-3-phospho-2 '-Hydroxyme Til-2 ', 5', 7 ', 8'-tetramethyl-6'-hydroxychroman, 1-stearoyl-2-palmitoylglycero-3-phospho-2'-hydroxymethyl-2', 5 ', 7' , 8'-tetramethyl-6'-hydroxychroman, etc.), L-carnosine zinc complex, umbelliferone, esculin, benzyl cinnamate, cinoxalate, oxybenzone, dioxybenzone, octabenzone, thrisobenzone, benzoresorcinol, arbutin, guaiazulene, Shikonin, baicalin, baicalein, berberine, neoheliopan, chlorophylls, xanthophylls, escalol, zinc oxide, talc, kaolin, anthracnose (benzoic acid) extract, hub extract, giant clover extract, cassava extract, kawatake extract, islet jellyfish extract , Hassai extract, Spirulina extract AIA Casio extract, funori Nou storm extract, Hime Gelidium extract, high Gelidium extract, Oobusaekisu, Chinorimoekisu, and the like.

(11) Astringents Specifically, succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc p-phenolsulfonate, potassium aluminum sulfate, resorcin, ferric chloride, tannins (tannic acid, Hamelian tannins, acer tannins, tetragalloyl glucose, pentagalloyl glucose, hexagalloyl glucose, heptagalloyl glucose, octagalloyl glucose, nonagaroyl glucose, decagalloyl glucose, undecagalloyl glucose, dodecagaro Gallotannins such as ilglucose, telimaglandin I, telimaglandin II, casarictin, peduncraggin, geraniin, isotarkebin, granatin A, granatin B, ketulinic acid, keblagic acid, casuarine, nuphalin, procyanidin -2, ellagitannins such as thiacinensin A, thiacinensin B, etc.), red grape extract, azuki bean (red bean) extract, altea extract, nettle extract, cascarilla extract, kapok extract, guarana extract, ezo strawberry extract, Dutch strawberry extract, shrimp Gara Strawberry Extract, Nawashiro Strawberry Extract, Momiji Strawberry Extract, European Raspberry Extract, Kidachi Aloe Extract, Hawthorn Extract, Kousuihakka Extract, Cowberry (Koshitachi) Extract, Cola Vera Extract, Sugarcane Extract, Sinah Honoki Extract, Honeysuckle (Gin Silver Flower, Shinobifu) Extract , Horsetail extract, Japanese larch extract, elder extract, dandelion extract, centalium extract, white dandelion extract, mouko dandelion extract, vine azuki bean extract , Tsurutsuchiakebi extract, Teuchigurumi extract, Tormentilla extract, Novara extract, Buttercup extract, Hagoromogusa extract, Castor extract, Grape extract, Prunes extract, Veronica extract, Bisnaga extract, Bilberry extract, Manshugurumi extract, Mitsuga wrinkle extract, Myrrh extract, Melissa Examples include extract, witch hazel extract, bay willow extract, latania (chlamelia) extract, lemon extract, chickpea extract and the like.

(12) Anti-inflammatory agent / interleukin production inhibitor / histamine release inhibitor Specifically, quinolinone derivatives, dibenzooxepin derivatives, thiotroposin, phthalimide derivatives, flurbiprofen, felbinac, bufexamac, suprofen, 1,4 -Diphenylpropylpiperazine derivatives, carxin compounds, chromanol glycosides (2- (α-D-glucopyranosyl) methyl-2,5,7,8-tetramethylchroman-6-ol), ictamol, indomethacin, kaolin, diphenhydramine hydrochloride , D-camphor, DL-camphor, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, hydrocortisone, guaiazulene, camazulene, chlorpheniramine maleate, diphenhydramine hydrochloride, clemastine fumarate, cyproheptadine hydrochloride, Acid promethazine, piperazine derivatives, α-D-phenylglycoside derivatives, glycyrrhizic acid or salts thereof and derivatives thereof (α-glycyrrhizic acid, β-glycyrrhizic acid, α-glycyrrhizic acid methyl ester, β-glycyrrhizic acid methyl ester, α- Trisodium glycyrrhizinate, monopotassium α-glycyrrhizinate, dipotassium α-glycyrrhizinate, monoammonium α-glycyrrhizinate, trisodium β-glycyrrhizinate, monopotassium β-glycyrrhizinate, dipotassium β-glycyrrhizinate, β-glycyrrhizic acid mono Ammonium), glycyrrhetinic acid or its salts and derivatives thereof (α-glycyrrhetinic acid, β-glycyrrhetinic acid, stearyl of α-glycyrrhetinic acid, stearyl of β-glycyrrhetinic acid, pyridoxine of α-glycyrrhetic acid , Β-glycyrrhetinic acid pyridoxine, α-glycyrrhetinic acid glycerin, β-glycyrrhetinic acid glycerin, 3-succinyloxyglycyrrhetinic acid disodium, etc.), mefenamic acid, phenylbutazone, ibuprofen, ketoprofen, allantoin, calcium pantothenate, pantothenylethyl Panthenol such as ether or salts thereof and derivatives thereof, ε-aminocaproic acid, diclofenac sodium, tranexamic acid or derivatives thereof (trans-4-benzyloxycarbonylaminomethylcyclohexanecarboxylic acid, trans-4-p-nitrobenzyloxycarbonyl Aminomethylcyclohexanecarboxylic acid, trans-4-p-chlorobenzyloxycarbonylaminomethylcyclohexanecarboxylic acid, trans-4-p-bromobenzyloxycarbo Ruaminomethylcyclohexanecarboxylic acid, trans-4-m-chlorobenzyloxycarbonylaminomethylcyclohexanecarboxylic acid, trans-4-p-methoxybenzyloxycarbonylaminomethylcyclohexanecarboxylic acid, trans-4-p-methylbenzyloxycarbonylamino Methylcyclohexanecarboxylic acid, sodium trans-4-benzyloxycarbonylaminomethylcyclohexanecarboxylate, ammonium trans-4-p-nitrobenzyloxycarbonylaminomethylcyclohexanecarboxylate, trans-4-p-chlorobenzyloxycarbonylaminomethylcyclohexanecarboxylic acid Potassium acid, potassium trans-4-p-bromobenzyloxycarbonylaminomethylcyclohexanecarboxylate, trans-4-m-chlorobenzyloxycarbo Calcium ruaminomethylcyclohexanecarboxylate, trans-4-p-methoxybenzyloxycarbonylaminomethylcyclohexanecarboxylate magnesium, trans-4-p-methylbenzyloxycarbonylaminomethylcyclohexanecarboxylate monoethanolamine, trans-4-t- Butyloxycarbonylaminomethylcyclohexanecarboxylic acid, trans-4- (2-phenylisopropyloxycarbonylaminomethyl) cyclohexanecarboxylic acid, trans-4- (p-biphenylisopropyloxycarbonylaminomethyl) cyclohexanecarboxylic acid, trans-4- ( 3,5-dimethoxyphenylisopropyloxycarbonylaminomethyl) cyclohexanecarboxylic acid, trans-4- (p-methylphenylisopropyloxycarbonylaminomethyl) Chlohexanecarboxylic acid, sodium trans-4-t-butyloxycarbonylaminomethylcyclohexanecarboxylate, potassium trans-4- (2-phenylisopropyloxycarbonylaminomethyl) cyclohexanecarboxylate, trans-4- (p-biphenylisopropyloxy) Carbonylaminomethyl) calcium cyclohexanecarboxylate, trans-4- (3,5-dimethoxyphenylisopropyloxycarbonylaminomethyl) magnesium cyclohexanecarboxylate, trans-4- (p-methylphenylisopropyloxycarbonylaminomethyl) cyclohexanecarboxylic acid monoethano -Luamine, trans-4- (9-fluorenylmethyloxycarbonylaminomethyl) cyclohexanecarboxylic acid, trans-4-methylsulfonylethyloxycarbonyl Ruaminomethylcyclohexanecarboxylic acid, trans-4- (9-fluorenylmethyloxycarbonylaminomethyl) sodium cyclohexanecarboxylate, potassium trans-4-methylsulfonylethyloxycarbonylaminomethylcyclohexanecarboxylate, trans-4- (pyridine -4'-methyloxycarbonylaminomethyl) cyclohexanecarboxylic acid, trans-4- (2,2,2-trichloroethyloxycarbonylaminomethyl) cyclohexanecarboxylic acid, trans-4- (2-trimethylsilylethoxycarbonylaminomethyl) cyclohexane Potassium carboxylate, trans-4- (pyridine-4′-methyloxycarbonylaminomethyl) cyclohexanecarboxylate sodium, trans-4- (2,2,2-trichloroethyloxycarbonylaminomethyl) cyclohexane Potassium carboxylate, trans-4- (2-trimethylsilylethoxycarbonylaminomethyl) cyclohexanecarboxylate, etc.), sulfatide, astaxanthin fatty acid diester (astaxanthin dilaurate ester, astaxanthin dimyristate ester, astaxanthin dipentadecanoate ester, astaxanthin diester Palmitic acid ester, astaxanthin dipalmitooleic acid ester, astaxanthin diheptadecanoic acid ester, astaxanthin dielaidic acid ester, astaxanthin diricinoleic acid ester, astaxanthin petrothelinic acid ester, astaxanthin vacsenate ester, astaxanthin eleostearic acid ester, astaxanthin Punicic acid ester, Astaxa Nanthric acid ester, astaxanthin parinalic acid ester, astaxanthin gadoric acid ester, astaxanthin 5-eicosenoic acid ester, astaxanthin 5-docosenoic acid ester, astaxanthin cetolic acid ester, astaxanthin erucic acid ester, astaxanthin 5,13-docosadienoic acid ester, Astaxanthin ceracholic acid ester, astaxanthin decenoic acid ester, astaxanthin stering acid ester, astaxanthin dodecenoic acid ester, astaxanthin dioleic acid ester, astaxanthin distearic acid ester, astaxanthin dieicosapentaenoic acid ester, astaxanthin didocosahexaenoic acid ester, astaxanthin dilinoleic acid ester, Astaxanthin Giri Rexic acid ester, astaxanthin diarachidonic acid ester, etc.), astaxanthin diglycerophosphoric acid ester (astaxanthin diglycerophosphoric acid ester, astaxanthin lyserophosphoric acid palmitic acid, astaxanthing lyserophosphatidylcholine palmitic acid, astaxanthing lyserophosphatidylcholine DHA, astaxanthing lysero Phosphatidylinositol palmitic acid, astaxanthing lyserophosphatidylinositol DHA, astaxanthing lyserophosphatidylinositol linoleic acid, astaxanthing lyserophosphatidylcholine linoleic acid, steviol glycosides, benzimidazole derivatives (1- (2-ethoxy) Ethyl) -2- [1- (2- (4- (1- (4,4-dimethyl-2-oxazolin-2-yl)- 1-methylethyl) phenyl) ethyl) piperidin-4-yl] -1H-benzimidazole, 2- [4- (2- (4- (1- (2-ethoxyethyl) benzimidazol-2-yl) piperidine- 1-yl) ethyl) phenyl] -2-methylpropanoic acid, ethyl 2- [4- (2- (4- (1- (2-ethoxyethyl) benzimidazol-2-yl) piperidin-1-yl) ethyl ) Phenyl] -2-methylpropanate, 1- (2-ethoxyethyl) -2- [1- (2- (4- (1,1-dimethyl-2-hydroxyethyl) phenyl) ethyl) piperidine-4- Yl] -1H-benzimidazole, 1- (2-hydroxyethyl) -2- [1- (2- (4- (1- (4,4-dimethyl-oxazolin-2-yl) -1-methylethyl) Phenyl) ethyl) piperidin-4-yl] -1H-benzimidazole, 2- [4- (2- (4- (1- (2-hydroxyethyl) benzimidazol-2-yl) piperidin-1-yl) ethyl ) Fe Ru] -2-methylpropanoic acid), alanine derivatives or salts thereof (N- {3-isopentyl-4-methyl-2- [4- (3-trifluoromethylbenzamido) benzoylimino] -3H-thiazoline-5 -Carbonyl} -L-alanine, N- {3-isopentyl-4-methyl-2- [4- (3-trifluoromethylbenzamido) benzoylimino] -3H-thiazoline-5-carbonyl} -2-methylalanine, N- {3-isopentyl-4-methyl-2- [4- (3-trifluoromethylbenzamido) benzoylimino] -3H-thiazoline-5-carbonyl} -N-methyl-L-alanine etc.), thiazoline derivatives or Its salt (3-isopentyl-4-methyl-2- [4- (3-trifluoromethylbenzamido) benzoylimino] -3H-thiazoline-5-carboxylic acid, 4-isobutyl-3-methyl-2- [4- (3-Trifluoromethylbenzamido) benzoylimino] -3H-thiazoline-5-ca Rubonic acid, etc.), chlorpheniramine maleate, diphenhydramine hydrochloride, diphenylpyraline hydrochloride, carbinoxamine maleate, hydrocortisone butyrate, sulfated acid mucopolysaccharide or salt thereof, sulfated dextran or salt thereof, fluoromethylhistidine or hydrochloride salt thereof, Histidine methyl ester or its hydrochloride salt, licorice extract, chicory extract, age extract, propolis, eye (Aiba) extract, asenyaku (Asenyaku) extract, avocado extract, amadokororo (tamatake) extract, amiga lily extract, baimo (shellfish mother) Extract, igakozorina (ground bile head) extract, ibukitoranoo extract, turmeric (depressed gold) extract, echina (hosobamurasakibarengiku extract), oren (yellow chain) extract, oguruma (turned over) extract, hypericum (young brother cut grass) extract, sea urchin extract , Oren Extract, cassia extract, chamomile extract (weed) extract, kawamidori extract, cormorant mugwort (bamboo chin moth) extract, watercress extract, kenashi sartorii rose (earthen soil, mountain return) extract, gentian extract, koki-sekoku extract, kakuhon (bamboo shoot, carp bonito) extract, Koryo Kyo (Kora Kaki) Extract, Gosho Strawberry (Cover Bonsai) Extract, Psychiaran Extract, Cherries Extract, Salvia (Sage) Extract, Diquitaris Extract, Linden Extract, Salamander Extract, Indian Bodge Extract, Shukushamitsu (Sanjin, Shredded Sand) ) Extract, juzudama extract, shirominanten (southern berry extract), Kizota extract, psyllium extract, Achillea millefolium (milfoil) extract, Hirosanega extract, Takasago Gurihigotai (southeast indigo sashimi) extract, Takarabi (spine) Extract, Tachikaku Sou (Marika) Extract, Tamazaki Rakuji Extract, Tonin Extract, Chigaya Extract, Toga (Winter Eggplant) Extract, Dokudami (10 Medicines) Extract, Parsley (Netherlands Jelly) Extract, Hanabishi (Satsurishi, Shishitsuri) Extract, Hamasuge (Incense) (Bushi) extract, Hishi (Hishimi) extract, Bellows oyster extract, Japanese pod extract (southern rattan) extract, Bundou (mung bean) extract, Sandalwood extract, Butcher bloom extract, Pansy extract, Hosoba arabiku extract, Mizurutennansho ( (Tennan star) extract, pheasant (fruit) extract, miracle fruit extract, mulberry extract, peach (peach) extract, cornflower extract, yachi willow extract, mistletoe (willow parasite) extract, yabukouji (purple gold beef) extract, sagebrush extract, mugwort ) Extract, Rosemary (Mannenrou) Kisses, Scots wings extract, Jujusmo extract, Tamajusmo extract, Mizojusmo extract, Urushigusa extract, Pepper gulsa extract, Sardine extract, Akamok extract, Togemoku extract, Akaba extract, Maruba akaba extract, Harigane extract, Dulse extract, Una extract , Belladonna extract, cypress extract, haruni (skin peel, white skin, coconut leaf) extract, Aozulan extract, sakaneran extract, Sasabaginran extract, Chinese cabbage extract (including varieties and origin species) extract, valerian extract, primrose extract, Examples include senkyu extract, kyounin extract, honeysuckle extract, touki extract, fennel extract, and peppermint extract.

(13) Antiseborrheic agent Specifically, chroman derivatives, pyridoxine or salts thereof and derivatives thereof, pyridoxal or salts thereof and derivatives thereof, pyridoxamine or salts thereof and derivatives thereof, sulfur, Asa (aspen) extract , Nettle extract (continuous), Dutch mustard (watercress) extract, valerian extract (valerian root) extract, clematis extract, bear sebassikis, scallop extract, rosewood extract, horse chestnut extract, soybean (soybean) extract, Tokinsenka (marigold) Examples include extract, Chinese yam extract, yam extract, nosen-halen extract, Japanese cypress poppy (sect winter flower, winter winter leaf) extract, japonica extract, giant kelp extract, hijirimen extract, proboscis extract, hyus banori extract and the like.

(14) Antibacterial agents Specifically, acrinol, sulfur, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin or its hydrolyzate, alkyldiaminoethylglycine chloride solution, triclosan, sodium hypochlorite, chloramine T , Salicy powder, iodine compound, iodoform, 1-alkylcarbapenem compound, N-substituted azepane derivative or salt thereof, sorbic acid or salt thereof, propionic acid or salt thereof, salicylic acid or salt thereof, dehydroacetic acid, parahydroxybenzoic acid ester 2-keto-3-deoxyoctanoic acid fatty acid ester, inositol deoxy derivatives (such as quercitol), inositol unsaturated derivatives (such as chonditol), inositol dimethyl ether, methyl inositol, inositol Ether, inosamine, deoxyinosadiamine, shikimic acid, quinic acid, undecylenic acid, thiamine lauryl sulfate, thiamine lauryl nitrate, phenol, cresol, p-chlorophenol, p-chloro-m-xylenol, p-chloro-m-cresol , Thymol, phenethyl alcohol, o-phenylphenol, irgasan CH3565, halocarban, hexachlorophene, chlorohexidine, ethanol, methanol, isopropyl alcohol, benzyl alcohol, ethylene glycol, propylene glycol, 2-phenoxyethanol, 1,2-pentanediol, zinc Pyridione, chlorobutanol, isopropylmethylphenol, elemol, tiveverol, patchouli alcohol, nonionic surfactant (polyoxyethylene lauryl ether, poly Xylethylene nonylphenyl ether, polyoxyethylene octylphenyl ether, etc.), amphoteric surfactants, anionic surfactants (sodium lauryl sulfate, lauroyl sarcosine potassium, etc.), cationic surfactants (cetyltrimethylammonium bromide, benzalkonium chloride) Benzethonium chloride, methyl rosaniline chloride), formaldehyde, hexamine, brilliant green, malachite green, crystal violet, germal, photosensitizer 101, photosensitizer 201, photosensitizer 401, N-long chain acyl basic amino acid derivatives and acids thereof Addition salt, zinc oxide, hinokitiol, propolis, cucumber extract, agi (Ayu) extract, asunaro extract, alpinia extract, katsudai (suzukuku) extract, Inubilu (Honagainbuyu) extract, Aogateto extract, Haribiyu extract, Ayuyu extract, Hagatou extract, Hosonagabiyu extract, Enmeiso extract, Warbler extract, Usbasaicin extract, Hanasaishin extract, Halibut extract, Ominaeshi (defeated sauce) extract Choi extract, Kahoku salamander extract, chamomile extract, linden extract, red linden extract, yellowfin extract, caraway extract, betel extract, kumazasa extract, cranberry extract, grapefruit extract, celosia (chicken crown flower, (Chicken cot) extract, bay bay laurel extract, cinnabar rose (moon flower) extract, copaiba balsam extract, yamazakura extract, edhigashira extract, miyazakura extract, yoshino cherry extract, casamikura extract, kanzakura extract, Sugar beet extract, white pepper extract, scabbard extract, birch extract, cinnamon extract, sorrel extract Sowka (grass) extract, onion extract, chicory extract, Korean senile (蕪 夷) extract, tsuruna (apricot) extract, tokon (root) extract, leek (coconut) extract, leek extract, peach extract, patchouli extract, Astragalus extract, cypress extract, pimenta extract, Ayuyu extract, Amaranthus extract, Blackberry extract, Hop extract, Makuri (sea herb) extract, Magnolia sprenger extract, Mizokakushi ( (Harenen) extract, bee extract, purple (purple) extract, Moso Chrysanthemum extract, pokeweed (commercial land) extract, yucca extract, crocodile extract, lavender extract, forsythia extract, scallop extract, Obatonmata extract, Tochaka (Yakuzunamata) extract, red-bellied extract, anaaosa extract, human rush extract, Hironohito rush extract, Usuhito rush extract, irolo extract, shige extract, arame extract, tamaitake extract, tambanori extract, katanori extract, cherry blossom extract, fujimatsumo extract, kawamozuku extract, aokawa mozuku extract, hime wa mozuku extract, yakuchi (gachi) extract, etc. Is mentioned.

(15) Blood flow promoter / vascular stimulator Specifically, tocopherol or a salt thereof and a derivative thereof, tocotrienol or a salt thereof and a derivative thereof, cephalanthin, carpronium chloride, an eugenol derivative (acetyleugenol, methyleugenol, methylisoeugenol) , Ethyl eugenol, ethyl isoeugenol, eugenol salicylate, etc.), minoxidil, pepper tincture, nonyl acid vanillamide, cantalis tincture, ginger tincture, mint oil, L-menthol, camphor, benzyl nicotinate, cinnarizine, trazoline, acetylcholine, verapamil , Ikutamol, α-borneol, cyclandrate, nonylic acid valenylamide, capsaicin, gingerone, assembly extract, garlic extract, carrot extract , Aloe extract, Gentian extract, Toki extract, Ashitaba (Tomorrow) extract, Arnica extract, Ukiyagara (Sanryo) extract, Himewiku extract, Citrus unshiu (Chest) extract, Toucan beetle (coconut) extract, Oyster extract, Persimmon extract, Kina extract, Goldfish hen extract, Anemone beetle extract, Kubinjinsou extract, Kouhone (river bone) extract, Burdock (beef bowl, beef coconut) extract, Sagaki (Yamabachi) extract, Sinalengyo extract, Ginger extract, Shobu (bamboo root, radish) extract, hawthorn extract, sea bream (Otaku) extract, Daidai (orange peel) extract, tanjin (dansang) extract, thyme extract, chiketsu carrot (bamboo ginseng) extract, tsurudokudami (what neck crab) extract , Carrot (Yoteba ginseng) extract, Capsicum (bansho) extract, Toki (toll) , Scotchworm extract (Sadako), Natsumikan extract, elderberry (bone graft) extract, hazelnut (coconut) extract, Hashiridokoro (roth root) extract, mint (light load, thin load leaf) extract, Hamabou Fu (beach wind) extract, Higotai extract , Fujimodoki (Chojizakura, Camellia) extract, Black currant extract, Bodaiju (Aoki tree) extract, Merirot extract, Yuzu extract, Loquat extract, Japanese jelly extract, Hibiscus extract, Rosehip extract and the like.

(16) Antiandrogens Specifically, follicular hormones (estrone, estradiol, ethinyl estradiol, etc.), isoflavones, oxendron, 4 ', 5,7-trihydroxy-8-prenylflavanone, 4', 5,7-tri Examples include hydroxy-8-prenylflavone, 3,3 ′, 4 ′, 5,7-pentahydroxy-8-prenylflavone, nicorandil, cyclosporic acid, and the like.

(17) Inhibitors of structural proteolytic enzymes (elastase, collagenase, keratin protease, serine protease, integrin degrading enzyme, involucrin degrading enzyme, filaggrin degrading enzyme, laminin degrading enzyme, fibronectin degrading enzyme, proteoglycan degrading enzyme, etc.) / Structural proteolytic enzyme expression inhibitor Specifically, adenine derivatives (butanetriol-9-adenine and its phosphate adduct, propanediol-9-adenine and its phosphate adduct, pentanetriol-9-adenine and its Phosphoric acid adducts, carbostyril derivatives or salts thereof, dicarboxylic acids (glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, 1,9-nonamethylenedicarboxylic acid, 1,10-decamethylene Dicarboxylic ), Rosmarinic acid, ursolic acid, oleanolic acid, hydroxamic acid derivative, esculetin derivative, anthocyanidins, nordihydroguaiaretech acid, 20-carboxy-16-hydroxy-21-nor-5 α-7,9 (11)- Lanostadien-3,24-dione, ubiquinone, plastaquinone, yuglone, shikonin, quinizarin, alizarin, abietin, levopimar, betulin, α-amylin, catechin compounds (catechin, epigallocatechin, epigallocatechin gallate, epicatechin, epicatechin gallate, Catechin rhamnopyranoside catechin, etc.), diisopropyl fluorophosphate, (2R, 6R) -2,6-dihydroxy-4- (tert-butyldimethylsilyloxy)-(3Z) -heptene-1,7-dicarboxylic acid Dimethyl, N, N'-bis [(1S, 2R) -2-hydroxyindan-1-yl]-(2R, 6R) -2,6-dibenzylo Ci-4-hydroxyheptanedicarboxylic acid-1,7-diamide, (2R, 6R) -2,6-dihydroxy-4- (tert-butyldimethylsilyloxy) heptane-1,7-dicarboxylate, (2R, 6R) -2,6-Dibenzyloxy-4- (tert-butyldimethylsilyloxy) heptane-1,7-dicarboxylate, (2R, 6R) -2,6-dibenzyloxy-4- (tert- Butyldimethylsilyloxy) heptane-1,7-dicarboxylic acid, N, N'-bis [(1S, 2R) -2-hydroxyindan-1-yl]-(2R, 6R) -2,6-dibenzyloxy -4- (tert-butyldimethylsilyl) oxyheptane-1,7-dicarboxylic acid diamide, N, N'-bis [(1S, 2R) -2-hydroxyindan-1-yl]-(2R, 6R)- 2,6-dibenzyloxy-4-hydroxyheptane-1,7-dicarboxylic acid diamide, N, N'-bis [(1S, 2R) -2-hydroxyindan-1-yl]-(2R, 6R)- 2,4,6-trihydroxyheptane-1,7-dicarboxylic acid diamide, N, N'-bi [(1S, 2R) -2-hydroxyindan-1-yl]-(2S, 6S) -2,6-dibenzyloxy-4-hydroxyheptane-1,7-dicarboxylic acid diamide, (2S, 6S)- 2,6-dihydroxy-4- (tert-butyldimethylsilyloxy)-(3Z) -heptene-1,7-dicarboxylate, (2S, 6S) -2,6-dihydroxy-4- (tert-butyldimethyl) Silyloxy) heptane-1,7-dicarboxylate, (2S, 6S) -2,6-dibenzyloxy-4- (tert-butyldimethylsilyloxy) heptane-1,7-dicarboxylate, (2S, 6S) -2,6-Dibenzyloxy-4- (tert-butyldimethylsilyloxy) heptane-1,7-dicarboxylic acid, N, N'-bis [(1S, 2R) -2-hydroxyindan-1- Yl]-(2S, 6S) -2,6-dibenzyloxy-4- (tert-butyldimethylsilyl) oxyheptane-1,7-dicarboxylic acid diamide, N, N'-bis [(1S, 2R)- 2-Hydroxyindan-1-yl]-(2R, 6R) -2,6-dibenzyloxy 4-hydroxyheptane-1,7-dicarboxylic acid diamide, 3-[[4- (4-fluorophenoxy) -benzenesulfonyl]-(1-hydroxycarbamoylcyclopentyl) -amino] -propionic acid, 4- [4- (4-Fluorophenoxy) -benzenesulfonylamino] -tetrahydropyran-4-carboxylic acid hydroxyamide, 4- [4- (4-chlorophenoxy) -benzenesulfonylmethyl] -tetrahydropyran-4-carboxylic acid hydroxyamide, 3 -[[4- (4-Fluorophenoxy) -benzenesulfonyl]-(1-hydroxycarbamoylcyclobutyl) -amino] -propionic acid, 4- (4'-chlorobiphenyl-4-yl) -2- [2- (1,3-dioxo-1,3-dihydroisoindol-2-yl) -ethyl] -4-oxobutyric acid, {1- [4- (4-fluorobenzyloxy) -benzenesulfonyl] -2-hydroxycarbamoyl Pipette Gin-3-yl) -carbamic acid isopropyl ester, 2- [4- (4-fluorophenoxy) -benzenesulfonylamino] -N-hydroxy-2-methylfuropionamide, 3- [4- (4-fluorophenoxy) ) -Benzenesulfonyl] -2, N-dihydroxyfuropionamide, 3- (4-phenoxybenzenesulfonyl) -7-oxabicyclo [2.2.1] heptane-2-carboxylic acid hydroxyamide, (4-benzylbenzyl)- [2- (2,2-dimethyl-1-methylcarbamoylpropylcarbamoyl) -4- (4′-fluorobiphenyl-4-yl) -butyl] -phosphinic acid, 2-amino-3- [4- (4- Fluorophenoxy) -benzenesulfonyl] -N-hydroxypropionamide, and N-hydroxy-2- (4-phenylpiperidine-1-sulfonyl) -acetamide, Iris japonicum extract, Nepenthes (summer hay) extract, o Bananas beetle (Banaba) extract, Barley hawthorn extract, Hawthorn (Yamako) extract, Calahoo (Koh-Pak) extract, Guava extract, Garbage (Gomicho) extract, Shazenso extract, Atlantic rose extract, Hypericum perforatum extract, Octopus (breeding) extract , Hina Taiko Kozuchi (cow knee) extract, Honoki (Japanese Koshoku, Park) extract, American grape extract, European grape extract, Yama grape extract, Mandarin extract, Misaki psycho (Shibahu) extract, Ogon extract, Hypericum extract, Clara extract, Mulberry extract , Cinnamon extract, gentian pepper extract, comfrey extract, salvia extract, elderberry extract, sea bream extract, button pi extract, Aozulan extract, sakaneran extract, sasabagin orchid extract, varieties and origin species No) extract, Aono agave extract, sisal hemp extract, Adenophortriphylla extract, and the like.

(18) Structural protein synthesis promoter Specifically, ethanolamine derivatives, pentoxyphyllin, serine derivatives, geraniol, crocetin, methyl 4- (2-ethylhexyloxy) -2-hydroxybenzoate, 2-hydroxy-4- (3,5,5-trimethylhexyloxy) methyl benzoate, methyl 4-cyclohexylmethoxy-2-hydroxybenzoate, methyl 4- (2-cyclohexylethoxy) -2-hydroxybenzoate, 4- (3,7- Methyl dimethyl-6-octenyloxy) -2-hydroxybenzoate, ethyl 3- (2-ethylhexyloxy) -5-hydroxybenzoate, methyl 5- (2-ethylhexyloxy) -2-hydroxybenzoate, 2- Hydroxy-5- (3,5,5-trimethylhexyloxy) methyl benzoate, methyl 5- (2-cyclohexylethoxy) -2-hydroxybenzoate, 4-N-hexyloxy-2-hydroxy Methyl benzoate, methyl 2-hydroxy-4-N-octyloxybenzoate, methyl 4-N-decyloxy-2-hydroxybenzoate, methyl 5-N-hexyloxy-2-hydroxybenzoate, 4- (2- Ethylhexyloxy) -2-hydroxybenzoic acid, 2-hydroxy-4- (2,5,5-trimethylhexyloxy) benzoic acid, 4-cyclohexylmethoxy-2-hydroxybenzoic acid, 4- (2-cyclohexylethoxy)- 2-hydroxybenzoic acid, 4- (3,7-dimethyl-6-octenyloxy) -2-hydroxybenzoic acid, 3- (2-ethylhexyloxy) -5-hydroxybenzoic acid, 5- (2-ethylhexyloxy) ) -2-Hydroxybenzoic acid, 5- (2-ethylhexyloxy) -2-hydroxybenzoic acid, 2-hydroxy-5- (3,5,5-trimethylhexyloxy) benzoic acid, 5- (2-cyclohexylethoxy) ) -2-Hydroxybenzoic acid, 4-N-hexyl Oxy-2-hydroxybenzoic acid, 5-N-hexyloxy-2-hydroxybenzoic acid, 2-hydroxy-4-N-octyloxybenzoic acid, 4-N-decyloxy-2-hydroxybenzoic acid, N- (2 -Hydroxyethyl) -4- (2-ethylhexyloxy) -2-hydroxybenzamide, N-ethyl-4- (2-ethylhexyloxy) -2-hydroxybenzamide, 2-acetoxy-4-cyclohexylmethoxybenzoic acid, 4- (2-Ethylhexyloxy) -2-hydroxybenzoic acid sodium salt, 4-{(2E) -3,7-dimethyl-2,6-octadienyloxy} -2-hydroxybenzoic acid methyl ester, 4-{(2E) -3,7-dimethyl-2,6-octadienyloxy} -2-hydroxybenzoate, 5-{(2E) -3,7 dimethyl-2,6-octadienyloxy} -2-hydroxybenzoate Ethyl, 3-{(2E) -3,7-dimethyl-2,6-octadienyloxy} -2-hydroxybenzoate, 3- (2E) -3,7-dimethyl-2,6-octadienyloxy} -5-hydroxybenzoate, 4-{(2E) -3,7-dimethyl-2,6-octadienyloxy}- Ethyl 3-methoxybenzoate, 4-{(2E, 6E) -3,7,11-trimethyl-2,6,10-dodecatrienyloxy} -2-hydroxymethyl benzoate, 4-{(2E)- 3,7-dimethyl-2,6-octadienyloxy} -2-hydroxybenzoic acid (2E) -3,7-dimethyl-2,6-octadienyl, 4-{(2E) -3,7-dimethyl- 2,6-octadienyloxy} -2-hydroxybenzoic acid, 5-{(2E) -3,7-dimethyl-2,6-octadienyloxy} -2-hydroxybenzoic acid, 3-{(2E ) -3,7-dimethyl-2,6-octadienyloxy} -2-hydroxybenzoic acid, 3-{(2E) -3,7-dimethyl-2,6-octadienyloxy} -5-hydroxy Benzoic acid, 2-hydroxy-4-{(2E, 6E) -3,7,11-trimethyl-2,6,10-dodecatrienyloxy} benzoic acid, 4-{(2E) -3,7-dimethyl - 2,6-octadienyloxy} -3-methoxybenzoic acid, 2-acetoxy-4-{(2E) -3,7-dimethyl-2,6-octadienyloxy} benzoic acid, N- (2- Hydroxyethyl) -4-{(2E) -3,7-dimethyl-2,6-octadienyloxy} -2-hydroxybenzamide, 4-{(2E) -3,7-dimethyl-2,6-octa Dienylamino} -2-hydroxybenzoic acid, dimethyl-2,6-octadienyloxy} benzoic acid, N- (2-hydroxyethyl) -4-{(2E) -3,7-dimethyl-2,6 -Octadienyloxy} -2-hydroxybenzamide, 4-{(2E) -3,7-dimethyl-2,6-octadienylamino} -2-hydroxybenzoic acid, 3-dodecyloxybenzoic acid, 3- (12-hydroxydodecyloxy) benzoic acid, 4-dodecyloxybenzoic acid, 4- (12-hydroxydodecyloxy) benzoic acid, 3- (12-hydroxyoctadecyloxy) benzoic acid, 4- (12-hydroxyocta Siloxy) benzoic acid, 3- (11-hydroxyundecyloxy) benzoic acid, 4- (11-hydroxyundecyloxy) benzoic acid, 3-[(2E) -3,7-dimethyl-2,6-octadi Enyloxy) benzoic acid, 4-[(2E) -3,7-dimethyl-2,6-octadienyloxy] benzoic acid, 3-[(2E, 6E) -3,7,11-trimethyl-2, 6,10-dodecatrienyloxy) benzoic acid, 4-[(2E, 6E) -3,7,11-trimethyl-2,6,10-dodecatrienyloxy] benzoic acid, 4- [3,7- Dimethyl-9- (2,6,6-trimethyl-1-cyclohexen-1-yl) -2,4,6,8-nonatetraenyloxy] benzoic acid, 4- [3,4-dihydro-2,5 , 7,8-Tetramethyl-2- (4,8,12-trimethyltridecyl) -2H-1-benzopyran-6-oxy] benzoic acid, 4-[(2E, 6E) -3,7,11- Trimethyl-2,6,10-dodecatrienyloxy] benzamide, 4-[(2E) -3,7-dimethyl-2,6-octadienyloxy] benzamide, 4- (2-methyl 2-butenyloxy) benzamide, 4- (2-ethylhexyloxy) benzamide, 4-dodecyloxybenzamide, 4- (12-hydroxydodecyloxy) benzamide, 4- (12-hydroxyoctadecyloxy) benzamide, 4- (11 -Hydroxyundecyloxy) benzamide, 4- (10-hydroxydecyloxy) benzamide, 4-isostearyloxybenzamide, N- (2-hydroxyethyl) -4-[(2E, 6E) -3,7,11- Trimethyl-2,6,10-dodecatrienyloxy] benzamide, N, N-dimethyl-4-[(2E, 6E) -3,7,11-trimethyl-2,6,10-dodecatrienyloxy] benzamide N, N-di [(2E) -3,7-dimethyl-2,6-octadienyl] -4-aminobenzamide, 4- [N'-methoxycarbonyl-N-[(2E) -3,7-dimethyl -2,6-octadienylamino] benzamide, 4- [N-acetyl-N-[(2E) -3,7-dimethyl -2,6-octadienyl]] aminobenzamide, N- (2-hydroxyethyl) -4-[(2E, 6E) -3,7,11-trimethyl-2,6,10-dodecatrienyloxy] -2 -Hydroxybenzamide, N, N-diethyl-4-[(2E, 6E) -3,7,11-trimethyl-2,6,10-dodecatrienyloxy] -2-hydroxybenzamide, pea extract, Tosakamodoki extract , Ikanoashi Extract, Hosobonori Extract, Novonori Extract, Igis Extract, Keigi Extract, Harigigi Extract, Hanagigi Extract, Usuba Watanagi Extract, Moroitogusa Extract, Fumoitusa Extract, Hanayagi Extract, Willow Tree Extract, Moyuyurena Extract Examples include Kori extract, Prunus extract, Sasabayana Ginori extract, horseradish extract, merbou extract and the like.

(19) Mucopolysaccharide (hyaluronic acid, chondroitin sulfate, etc.) degrading enzyme inhibitors Specifically, anacardic acid or its derivatives (6-pentadecatrienylsalicylic acid methyl ether, 6-pentadecatrienylsalicylic acid ethyl ether, 6 -Pentadecatrienyl salicylic acid propyl ether, 6-pentadecatrienyl salicylic acid butyl ether, 6-pentadecatrienyl salicyl alcohol methyl ether, 6-pentadecatrienyl salicyl alcohol ethyl ether, 6-pentadecatrienyl salicyl alcohol propyl ether 6-pentadecatrienyl salicyl alcohol butyl ether, 6-pentadecatrienyl salicylaldehyde methyl ether, 6-pentadecatrienyl salicylaldehyde ethyl ether, 6-pentadecatrienyl salicyl aldehyde Dopropyl ether, 6-pentadecatrienyl salicylaldehyde butyl ether, 2-methyl ether-6-pentadecatrienyl cinnamic acid, 2-ethyl ether-6-pentadecatrienyl cinnamic acid, 2-propyl ether-6 -Pentadecatrienyl cinnamate, 2-butyl ether-6-pentadecatrienyl cinnamate, 2-methyl ether-6-pentadecatrienyl cinnamate alcohol, 2-ethyl ether-6-pentadecatrienyl cinnamate Skin alcohol, 2-propyl ether-6-pentadecatrienyl cinnamon alcohol, 2-butyl ether-6-pentadecatrienyl] cinnamon alcohol), polyisoprenylated benzophenone derivatives (garcinol, isogarcinol, xantho) Thymol, isoxanthothymol, gucciferon, etc.), Ikarisou extract, Yachima Taikiso (Yinyokukaku) extract, Narukoyuri extract, Kajikarumabanarukoyuri (Yellow spirit) extract, Oregano extract, Oshida extract, Onji extract, Spruce extract, Crow peony (Half summer) extract, Pheasant (fruit) extract, Japanese wolfberry (Bone skin) extract, Goshuyu extract, Senega extract, Sendan extract, Tamarind extract, Tarragon extract, Korean radish (Dahi) extract, Bee extract, Daisies extract, Milobaran extract, Himekuma willow extract , Mockin extract, Laurel extract, Yabusotatsu extract, Anaaasa extract, Macrocystis integolifolia extract, Neocitus Ruetkeana extract, Hiluxa extract, Oatweed extract, Caterpillar extract, Yatabegusa extract, Spotted rush extract, Ezo Nomata extract, Togetsumata extract, Fusaiwata extract, Hanemo extract, Mill extract, Cromil extract, Sakibuchimil extract, Nagar extract, Hiramil extract, Matsumo extract, Okinawa mozuku extract, Mozuku extract, Fukuronori extract, Kajime extract, Fukurofunori extract, Makuhori extract, grape leaf extract , Salamander extract, lotus extract and the like.

(20) Mucopolysaccharide synthesis promoter Specifically, stilbene derivatives or salts thereof, morgin or salts thereof and derivatives thereof, N-acetylglucosamine, flax extract, cinnamon extract, mulberry extract, scotch extract, breadfruit Extracts Examples of the extract include black beetle extract, nezushinosakamodoki extract, yusora extract, etsukinotosakamodoki extract, nankaitosakamodoki extract, himetosakamodoki extract, and the like.

(21) Intercellular adipogenesis promoter / intercellular lipid state improving agent Specifically, phospholipids (phosphatidylethanol, phosphatidylcholine, phosphatidyltriethanolamine, phosphatidylserine, phosphatidic acid, phosphatidylglycerol, phosphatidylinositol, diacylphosphatidylcholine, Diacylphosphatidylethanolamine, diacylphosphatidylinositol, diacylphosphatidylserine, 1-cysteinylphosphatidic acid, 2-cysteinylphosphatidic acid, 1-glutathionylphosphatidic acid, 2-glutathionylphosphatidic acid, 1-azelaoylphosphatidic acid 2-Azela oil phosphatidic acid, 1-hydroxyacyl phosphatidic acid, 2-hydroxyacyl phosphatidic acid, ceramide, glucosi Ceramide, galactosylceramide, cerebroside, phosphatidylglucosylacylglycerol, N-oleoylsphingosine, N- (12-hydroxyoctadecanoyl) sphingosine, N- (16-hydroxyhexadecanoyl) sphingosine, N-salicyloylphytosphingosine, Sphingomyelin, soybean lecithin, egg yolk lecithin, etc.), sterins (cholesterol, dihydrocholesterol, cholesteryl stearate, cholesteryl hydroxystearate, macadamia nut oil fatty acid cholesteryl, β-sitosterol, stigmasterol, campesterol, ergosterol, 5-dihydro Ergosterol, phytosterol, 25-hydroxycholesterol, 26-hydroxycholesterol, 19-hydroxycholesterol 22-ketocholesteroloxime, 6-ketocholesterol and 7-ketocholesterol or their derivatives), N-acetylneuraminic acid (sialic acid), N-glucosolneuraminic acid, gangliosides (galaose, ganglytriaose, Ganglitetraose, globotetraose, neolactotetraose, neolactohexaose, neolactooctaose, etc.), oligosulfated hyaluronic acid, hydroxytamoxifen compounds, glyceroglycolipids, pentoxyferrin, 3-deazaadenosine, Carboxamide derivatives, inositol polyamines, sialic acid, triterpenic acid derivatives, lactose, lactosamine derivatives, sulfated chitin derivatives, albumin, ginseng extract, tochiban ginseng extract, sea cucumber extract, red lily extract Hakata lily extract, poppy extract, and the like.

(22) Keratolytic agent / stratum corneum exfoliation accelerator Specifically, tropolone and its derivatives, resorcin, lactic acid, urea, salicylic acid, guanidine, ethanolamine, kikarasuuri (Gurone) extract, fenugreek extract, wisteria bean (shado) Extract, lentil extract, chickpea extract, mungbean extract and the like.

(23) Plasminogen activator antagonist inhibitor Specific examples include rabbit daisy extract, canamgra extract, caladium extract, raspberry extract and the like.

(24) Maillard reaction inhibitors Specifically, aminoguanidine, flavanones (naringin, naringenin, naringin, naringenin, liquiritin, liquiritigenin, digallic acid, luteoic acid, ellagic acid, chlorogenic acid, glucogallin, tetralin, hamamelitannin Tannic acid, tannic acid, tannic acid, geraniin, gallic acid, galloyl gallic acid, ellagitannin, hexagalloyl glucose, heptagalloyl glucose, tetragalloyl glucose, trigalloyl glucose, pentagalloyl glucose, digalloyl quinic acid, trigalloyl kinin Acid), 2-hydroxyphenylalkylamine derivatives or salts thereof, phenylpropenoic acid derivatives (3- [2,3-bis (methoxymethoxy) phenyl] propenoic acid, 7- (4-hydroxy-3-methoxyphenyl) hepta- 2,4,6- Trienoic acid, 3- (3,5-dimethoxy-4-hydroxyphenyl) propenohydrazide, N'-isopropylidene-3- (2-methoxyphenyl) propenohydrazide, etc.), citric acid or a salt thereof, ginger (Ishizuchi) Root) extract, sandalwood extract, red-crowned wrinkle extract, persimmon (including salmon) extract, mulberry extract, Hypericum perforatum extract, camellia extract, garega extract, yaba santa extract, rosehip extract, asunaro extract, itadori extract, icha yak extract, kei Kanka extract, Birch extract, Hawthorn extract, Achillea millefolium extract, Cod extract, Dokudami extract, Tormentilla extract, Bakumondo extract, Hiba extract, Grape extract, Michiyanagi extract, Mukuroji extract, Karin extract, Mokka extract, Roman kami Reekisu, and the like.

(25) Testosterone 5α reductase activity inhibitor / hair papilla activator / hair growth promoter Specifically, γ-amino-β-hydroxybutyric acid esters (γ-amino-β-hydroxybutyric acid methyl ester, γ-amino) -β-hydroxybutyric acid ethyl ester, γ-amino-β-hydroxybutyric acid propyl ester, γ-amino-β-hydroxybutyric acid butyl ester, γ-amino-β-hydroxybutyric acid ethylhexyl ester, γ-amino-β-hydroxybutyric acid hexa Decyl ester, γ-amino-β-hydroxybutyric acid lauryl ester, γ-amino-β-hydroxybutyric acid stearyl ester, γ-amino-β-hydroxybutyric acid oleyl ester, γ-amino-β-hydroxybutyric acid benzyl ester, γ-amino -β-hydroxybutyric acid phenyl ester, γ-amino-β-hydroxybutyric acid ethyl glycol ester, γ-amino-β-hydroxy Acid sorbitol ester, γ-amino-β-hydroxybutyric acid polyoxyethylene glycol ester, γ-amino-β-hydroxybutyric acid glycerin ester, etc.), amine oxides (oleyl dimethylamine oxide, stearyl dimethylamine oxide, palmityl dimethylamine oxide) , Myristyl dimethylamine oxide, lauryl dimethylamine oxide, dimethyl lauryl ethoxyamine oxide, dihydroxyethyl lauryl amine oxide, coconut oil alkyl dimethylamine oxide, etc.), alkyl betaines (coconut oil fatty acid amidopropyl betaine, coconut oil alkyl betaine, lauryl dimethyl) Aminoacetic acid betaine, lauric acid amidopropyl betaine, lauryl hydroxysulfobetaine, 2-alkyl-N-carboxymethyl-N-hydroxy Ethyl imidazolinium betaine), pyrimidine N-oxide derivatives (2-amino-4-methyl-6-piperidinopyrimidine-3-oxide, 2-amino-4-methyl-6- (1-pyrrolidinyl) pyrimidine- 3-oxide, 2-amino-4-methyl-6-morpholinopyrimidine-3-oxide, 2-amino-4-methyl-6- [1- (4-methylpiperazinyl)] pyrimidine-3-oxide, 2-amino-4- (1-hexahydroazepinyl) -6-methylpyrimidine-1-oxide, 2-amino-4-dimethylamino-6-methylpyrimidine-1-oxide, 2-amino-4-allylamino -6-methylpyrimidine-1-oxide, 2-amino-4-benzylamino-6-methylpyrimidine-1-oxide, 2-amino-4,5-methyl-6-piperidinopyrimidine-3-oxide, 2 -Amino-4-ethyl-6-morpholinopyrimidine-3-oxide, 2-amino-4-methyl-5-nitro-6-piperidinopyrimidine-3-io Sid, 2,5-diamino-4-methyl-6-piperidinopyrimidine-3-oxide, 2-amino-4-methyl-5,6-bis (1-pyrodinyl) pyrimidine-3-oxide, 2-amino -4-methyl-5-piperidino-6- (1-pyrrolidinyl) pyrimidine-3-oxide, 2-methyl-4-amino-6-piperidinopyrimidine-3-oxide, 2-methyl-4-amino-5 -Bromo-6- (1-pyrosinyl) pyrimidine-3-oxide, 2-methyl-4-amino-5-nitro-6-piperidinopyrimidine-3-oxide, 2-methyl-4,5-diamino-6 -Piperidinopyrimidine-3-oxide, 2-methyl-4-amino-5,6-bis (1-pyrrolidinyl) pyrimidine-3-oxide, 2-amino-4-methyl-6-piperidinopyrimidine-3 -Oxide monohydrochloride, 2-acetylamino-4-methyl-6-piperidinopyrimidine-3-oxide, 2,4-diamino-6-phenoxypyrimidine-3-oxide, 2,4-diamino-6- ( 2,4-dichlorophenoxy ) Pyrimidine-3-oxide, 2,4-diamino-6- (2,4,6-trichlorophenoxy) pyrimidine-3-oxide, 2,4-diamino-5-nitroso-6- (2,4-dichlorophenoxy) ) Pyrimidine-3-oxide, 2,4-diamino-5-nitro-6- (2,4,6-trichlorophenoxy) pyrimidine-3-oxide, 2,4-diamino-5-nitro-6- (2, 4-dichlorophenoxy) pyrimidine-3-oxide, 2,4,5-triamino-6- (2,4-dichlorophenoxy) pyrimidine-3-oxide, 2,4-diamino-5-bromo-6- (2, 4-dichlorophenoxy) pyrimidine-3-oxide, etc.), p-menthane-3,8-diol, monoglyceryl-D-glucoside monotridecanoate, 1-oN-pentadecylglycero-D-glucoside, mono Glycerol sulfate such as pentadecanoic acid glyceride sulfate, monopentadecyl glyceryl ether sulfate, 1-o-hexade -2-o-methylglycerol, 1-o-octadecyl-2-o-methylglycerol, 1-o-oleyl-2-o-methylglycerol, acetylcarnitine or a salt thereof, geranylgeranylacetone, Hydroxamic acid derivatives or salts thereof, gingerone glycosides, benzeneoxyacetic acid derivatives ([5- [2- [1-phenyl-1- (3-pyridyl) methylideneaminooxy] ethyl] -7,8-dihydronaphthalene- 1-yloxy] acetic acid, etc.), isorhamnetin-3-robinobioside, xanthone derivatives, proanthocyanidins (grape seed extract proanthocyanidins, apple-derived proanthocyanidins, pine-derived proanthocyanidins, purified procyanidin oligomers, procyanidin B-1, procyanidin B- 2, procyanidin B-3, procyanidin C-1, etc.), arakashi extract, angelica extract, anse ( Jin) extract, Hong apricot extract, Ichiyakusou (one herb) extract, Enishida extract, psyllium (car forerunner, car forerunner) extract, Psyllium extract , Chrysanthemum extract, striped chrysanthemum extract, ginseng extract, cuttlefish extract, kukui nut extract, camphor tree extract, kubeba extract, buckthorn extract, snapper extract, snapdragon extract, snapdragon extract, kipi extract, citrus extract, cilantro extract, kobushi extract, Magnolia extract, honeysuckle extract, binankazura extract, pine bush extract, colombo extract, condurango extract, sasanqua extract, sweet potato extract, honeybee jujube ( (Jinjin) Extract, Sandskon (Yamadame) Extract, Potato Extract, Shishigashira Extract, Sanshishi Extract, Coriander Extract, Stevia Extract, Takatodai Extract, Tarayou (Ooba Fuyu Ao, Ichiha Tea, Bitter Tea, Tofu Tea) Extract, Taran Extract, Nigaki (Nagi) Extract, Nurde (Pyto) Extract, Hakama Labosi (Bone Disintegrating) Extract, Hamakokuren Extract, Smoke Squirrel Extract, Sphagoptera Extract, Hakakugusa (Sugar) Extract, Hyacinth Carrot Extract, Mangosteen Extract, Myouga Extract, Melaleuca Extract, Yachabushi (Yagar) Extract, Himeya Shabushi Extract, Ooyabaya Shabushi Extract, Yakuso Extract, Yamahanoki (Yamatake) Extract, Longan (Dragon Eye Meat) Extract, Locon (Yoshi, Sone) Extract , Logwood extract, lantana extract, etc. .

(26) Hair matrix growth inhibitor / hair growth inhibitor Specifically, phthalazinones, benzoxazinones, phosphonic acid derivatives, cyproterone, 5α-androstene-3α, 17β-diol, medroxyprogesterone, norethisterone, Examples include Mestanolone, Ichihatsu (primary) extract, Kashiwa extract, Kantou extract, Sanjiko extract, Shiramo extract, Sowjutsu extract, Hitobushi licorice extract, Fritillary extract, Iris japonica extract, Iris extract and Yoremok extract.

(27) Hair swelling / protecting agent Specific examples include ethanolamine, urea, guanidine, silicones, blueberry extract, mango extract, and the like.

(28) Odorous substance scavengers Specific examples include Inondo extract, Elemi extract, Danmar extract, vanilla bins extract, pine extract and the like.

  Specific examples of ingredients derived from plant-based materials used as additives include Aokazura (Seifu-to) extract, Aotenma extract, Akasuguri extract, Aquine (crust) extract, Aguay guassu extract, Abiul extract, Abiurana Extract, yellow sapote extract, ylang ylang extract, phalaenopsis extract, uba tea extract, suzuran extract, unboku extract, elderberry extract, sasayukiyuki extract, sasanoyuki extract, tossed cactus extract, ohia catechu extract, onoelan extract, cynomolgus (Kinshato) extract, karaya extract, garyu extract, kawaratake extract, candelilla extract, canna extract, beetle mint extract, kimenakaku extract, cabbage extract, kiraja saponaria extract, ginsekai extract, kimbusenki , Guapeba vermela extract, kugenumaran extract, cousberry extract, cutiti river extract, curkurigo rachifolia extract, black moth (rescue) extract, cucumber extract, sapotea mariyo extract, salmon berry extract, salamander (sand indigo) (Sashimi) extract, Cactus cactus extract, Cinnamon extract, Shunran extract, Shozuk extract, Shirobanatsuta extract, Cinacna sylbra extract, Swimberry extract, Star apple extract, Sulgaran (Oran) extract, Red pine extract, Cypress extract , Pearl moth extract, mistletoe extract, sennin cactus extract, senboku extract, elephant weevil extract, cinnamon waxy extract, some mono-potato extract, dark sweet Jelly extract, peony extract, choconostay extract, Korean mugwort extract, horsetail extract, cicada extract, cicada extract, dubery extract, cicada extract, tragacanth extract, triacanthus extract, nigeria Berry extract, Rapeseed extract, Plover-dough extract, Pau-dose extract, Hakukayumatou extract, Hakuru-berry extract, Batata extract, Hamakakiran extract, Balata extract, Harcan orchid extract, Pecan nut extract, Hinori duck extract, Himemuyoran extract , Brazilian carrot extract, Branjen extract, Frucereria extract, Blond psyllium extract, Hetsukaran extract, Henken extract, Berry extract, Persea extract, Pervianburg extract, Perez A Grandifolia extract, Boysenberry extract, Hosairan extract, Pouteria sapota extract, Pouteria rukuma extract, Hosobabarengiku extract, Whataberry berry extract, Mazaran bauba extract, Masala nuba de ceara extract, Masheira de Boyi extract , Matta Oryo Extract, Mulberry Extract, Green Zapote Extract, Murasaki Corn Extract, Megacansa Opuntica Extract, Mokukirin Extract, Momijidaio Extract, Morello Cherry Extract, Yakawa Murasaki Imo Extract, Cornflower Extract, Rurita Thistle Xinjiang indigo head extract, plant extract such as red currant extract, red pitaya extract, lemongrass extract, wax palm extract, logan berry extract, etc. It is done.

  Specific examples of the ingredients derived from plant-based materials used as additives include Dunaliella genus Dunaliella extract, Chlorococcus chlorococcus extract, Anemone genus Anemone extract, Volbox genus genus extract, Volbox genus Volbox extract, Palmera extract, Jupiter extract, Aomydra spp. Extract, Papilio spp. Extract, cassava extract, cicada extract, colecaete extract, cicada extract, duckweed extract, crayfish Green extract such as Loa extract, Kunshomo extract, Sumiremo violet extract, Hosimidro extract, Fuchinashimidro extract Iso Grape Extract, Isogawara Isogawara Extract, Kurogashira Gunsen Kurogashira Extract, Kashirazaki Kashirazaki Extract, Muchimo Muchimo Extract, Muchimo Hiramchimo Extract, Muchimo Keribergusa Extract, Amygusa Sakibiro Amiji Extract, Common Sasa Common Gusa Extract, Jigamigusa Genus Jigmyusa extract, Nami-makura genus Hirami-makura extract, Someraceae genus Someraceae extract, Navaimo genus Navarimo extract, Chasomen moth Chasomen extract, Nagamatsu sp. Nagamatsu sp. Rabbit extract, Raspberry spp., Rabbit spp. Weeping Manori Extract, Weeping Crab Extract, Fritillaria Fistula Extract, Cultivation Crane Extract, Frog Brown algae extract such as genus Chlome extract, Chrysanthemum genus Chrysanthemum extract, Nerecomb genus Nerecomb extract, Spirella spp. Extract, Amanori Tasa Extract, Amanori Firitasa Extract, Amanori Benitasa Extract, Rhodocorton Mirnoveni Extract, Kona Hada Hyakona Hada Extract, Kona Hada Yokore Kona Hada Extract, Kona Hada Ao Naha Hada Extract, Rhizobium Genus Thrips Gassilori extract, pine genus pine extract, Nisefusanori genus Fusanoori extract, Sodegarami genus Sodegarami extract, Hirohata Tadaki genus Hirohata Mitaki extract, Amanita Nambugusa extract, Tengususa spp. Pseudomonas spp. Crabnote extract, Coral spider coral extract, Centipede spruce cadaver extract, Centipede spruce extract, Centacum spp. Denori genus centipede extract, centipede genus vine extract, centipede genus fudarak extract, genus genus marbahudarak extract, cypress genus cypress extract, arabe genus madder extract, quince genus chabo kintoki extract, kinto genus kintoki extract Pine extract, Kintoki-Hitomatsu extract, Kintoki-Bushiki-toki-toki extract, Kintoki-tsunomu-kade extract, Kintoki-toga-kinki-toki extract, Kintoki-suji-kadeki extract, Kakera-to-spotted oakkin-toki extract, Nagaobane-genus Nagaobane extract, Kalekigusa-kalekigusa extract, Kinuhada Genus Kinu Hada extract, Tsukasanoori Enashikarimenia extract, Tsukasanoori Otsukasanori extract, Tsukasanoori Hanagatakarimenia extract, Ho Genus honoo extract, genus genus genus genus extract, genus genus genus Usugineu extract, genus genus genus genus urchinum extract, venus nago genus venus nago extract, skunk genus suskake beni extract, okaramusa genus genus extract, isomocca genus isomokka extract, pheasant genus pheasant extract Isodantsu Isodantsu Extract, Atsubanori Atsubanori Extract, Ogonori Mizookonori Extract, Ogonori Beniogonori Extract, Ogonori Fucreshinori Extract, Ogonori Murasaki-bibanori Extract, Ogonori Shinkabanori Extract, Ogonori Tokagenori Extract, Ogonori genus Katagogonori extract, Ogonori genus Ryukyu Ogonori extract, Ogonori genus Ogonori extract, Ogonori genus Ituginu extract, Ogonori genus Yumi Ganoderma extract, Ogonori genus Kubileogonori extract, Ronus spruce genus extract, Ronus spp. Scorpion genus extract, Rhizoma genus extract, Sedum genus extract, Scots squirrel extract, Scutella genus extract, Scutella genus extract, Scutella genus extract, Scutella genus extract, Fukutsunagi extract Hanaedae extract, Hirata goat Hirata goat extract, Dulse scorpion extract, Dulse anadalus extract, Webagus webag Extract , Konohanori extract, Suzushironori extract, Usbeni spp.usbeni extract, Hasujiginu spp. Hyus vanori genus Suusus banori extract, Hyus banori genus Hyus banori extract, Usubanorimodoki genus Usubanorimodoki extract, Ayanishiki genus Ayanishiki extract, Goatium Aeginu Extract, Dadia Enasidadia Extract, Shimadadia Isohagi Extract, Shimadadia Shimadadia Extract, Dajimodaki Dajimomodoki Extract, Makuri Makuri Extract, Hanegusa Hanagusa Extract, Hanegusa Kehanegusa Extract, Kozanemo Kozaemone Kozaemone Cozanemo sp. Red algae such as Isobasho genus Isobasho extract, Ideukogome genus Yukogome extract, Ochimodoku genus Okichimozuku extract, Chisujinori genus Chisujinori extract Extracts, Shajikumo Extract, Shirahamamo Extract, Hoshitsurimo Hoshitsurimo Extract, Rikunotumnusu Extract, Flasmocha spp. It is done.

  Specific examples of ingredients derived from animal materials used as active ingredients or additives include chicken crown extract, cow, pig or human placenta extract, pig or cow stomach, duodenum, intestine, spleen extract or degradation products thereof. , Bovine or porcine brain tissue extract, water-soluble collagen, collagen derivatives such as acylated collagen, collagen hydrolysate, elastin, elastin hydrolysate, water-soluble elastin derivative, keratin and its degradation product or derivatives thereof, silk Proteins and degradation products thereof or derivatives thereof, porcine or bovine blood cell protein degradation products (globin peptides), cattle or pig hemoglobin degradation products (hemin, hematin, heme, protoheme, heme iron, etc.), milk, casein and degradation thereof Products or derivatives thereof, skim milk powder and decomposition products thereof or derivatives thereof, lactoferrin or decomposition products thereof, chicken egg formation , Fish hydrolyzate, nucleic acid-related substance (ribonucleic acid, deoxyribonucleic acid), and the like.

  Specific examples of components derived from microbial materials used as active ingredients or additives include yeast metabolites, yeast extract extracts, bacterial metabolites, bacterial extract extracts, metabolites such as molds or mushrooms, actinomycetes metabolites , Extracts such as mold or mushroom, actinomycetes extract, natto metabolite, natto extract, fermented rice extract, fermented rice bran (red rice bran, birch) fermented extract, euglena extract or its degradation products or their water-soluble derivatives, raw milk Or the lactic acid fermented product of skim milk powder, a trehalose, its derivative (s), etc. are mentioned.

  In addition, as a plant, animal, or microbial material, any site, cell, tissue, organ, metabolite, etc. derived from a transgenic body or a cell fusion can be used. Furthermore, it is obtained by culturing cells of any site, cell, tissue, organ, etc., for example, cultured cells derived from each tissue (cultures derived from animals such as fibroblasts, Langerhans cells, macrophages, epidermal cells, hepatocytes, etc.) Cell etc.), undifferentiated cell group, cell group in the middle of differentiation, and their metabolites can also be used.

  Specific examples of components of natural raw materials used as active ingredients or additives include seawater such as deep seawater, for example, sea salt, seawater dried product, Dead Sea, Atlantic Ocean or Pacific Ocean. Sodium, magnesium chloride, potassium chloride, etc.), sea mud or mud (fungo), for example, sea mud or mud in various places such as Italian fungo, German fungo, Eifelfango, Freiburg fungo (containing components: silicon dioxide, titanium dioxide, Aluminum oxide, iron oxide, manganese oxide, sodium oxide, potassium oxide, magnesium oxide, calcium oxide, strontium oxide, sodium, potassium, magnesium, calcium, chromium, iron, copper, nickel, zinc, lead, manganese, arsenic, water) , Saintoku stone, natural smectite, bentonite, hectorite, etc. It is.

  Extracts derived from plant-based raw materials, animal-based raw materials, microbial-based raw materials, and other natural product raw materials used as active ingredients or additives are processed in a conventional manner according to the product type and form to be added (for example, pulverized) , Milling, washing, extraction, degradation, fermentation or metabolic conversion by microorganisms, fractionation, purification, pressing, filtration, drying, powdering, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization, etc. It is only necessary to select and use any of various materials.

  The solvent used for extraction may be selected in consideration of the intended purpose and type of the product to be provided or the processing to be performed later. Usually, water, methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol, isopropanol are used. Lower alcohol such as butanol or hydrous lower alcohol, propylene glycol, 1,3-butylene glycol, 1,2-butylene glycol, 1,4-butylene glycol, 1,5-pentanediol, 1,2-pentanediol, 1, Polyhydric alcohols such as 3-pentanediol, 1,4-pentanediol, 1,3,5-pentanetriol, glycerin, polyethylene glycol (molecular weight 100 to 100,000) or water-containing polyhydric alcohols, acetone, ethyl acetate, diethyl ether , Dimethyl ether, ethyl methyl ether, dioxane, acetonitrile, Various organic solvents such as silene, benzene, chloroform, carbon tetrachloride, phenol, toluene, etc., acids (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, etc.) and alkalis (sodium hydroxide, water, etc.) prepared as appropriate. It is desirable to use one or a mixture of two or more selected from potassium oxide, calcium hydroxide, ammonia and the like. However, when it is not preferable to contain a solvent depending on the application, it is sufficient to use only water or ethanol that can be easily removed after extraction, and it can be used alone or in any mixture with water. What was extracted may be sufficient.

  Regarding the extraction method, the temperature of the solvent, the weight ratio of the solvent to the raw material, or the extraction time can be arbitrarily set for various raw materials and the solvent used. Although it can set arbitrarily as the temperature of a solvent in the range of -4 degreeC to 100 degreeC, 10-40 degreeC vicinity is preferable from the point of stability of the component contained in a raw material. Further, the weight ratio of the solvent to the raw material can be arbitrarily set within the range of, for example, the raw material: solvent is 4: 1 to 1: 100, and the weight ratio of 1: 1 to 1:10 is particularly preferable.

  Decomposition mainly includes acid decomposition, alkali decomposition, enzyme decomposition, and high-temperature and high-pressure decomposition. In the decomposition with an acid, for example, it is preferable to use an inorganic acid or an organic acid such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, formic acid, oxalic acid, hydrogen bromide, perchloric acid, and periodic acid. In the decomposition by alkali, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, barium hydroxide, sodium carbonate, ammonium carbonate, calcium carbonate, magnesium hydroxide, sodium silicate, etc. are preferably used. In the decomposition with acid or alkali, the concentration, reaction time, reaction temperature, and the like can be arbitrarily set for the target raw material. In the enzymatic degradation, it is preferable to use an enzyme having a function of degrading proteins, polysaccharides, lipids or complexes thereof having an important function particularly with respect to cell structure, tissue structure, etc., for example, aminopeptidase, dipeptidase, dipeptide Peptidyl peptidase, tripeptidyl peptidase, carboxypeptidase, serine protease, trypsin, chymotrypsin, cysteine protease, thiol protease, papain, aspartate endopeptidase, metalloendopeptidase, promeline, thermolysin, pronase, pepsin, rennin, Proteolytic enzymes (proteases) such as pancreatin, chymopapain, ficin, collagenase, elastase, amylase, takaamylase, cellulase, hemicellular Polysaccharide-degrading enzymes such as zectin, pectinase, polygalacturonase, dextranase, and plalanase, hen egg white lysozyme, human lysozyme, papaya lysozyme, cabra lysozyme, barley lysozyme, zymolyce, lysozyme chloride, glucanase, gluco Examples include cell wall lytic enzymes such as uronidase, chitinase, and kilosanase. In the case of using an enzyme, the concentration, reaction time, reaction temperature, pH of the solution, and the like can be arbitrarily set, but it is particularly preferable to set the optimum value for the enzyme used.

Fermentation or metabolic conversion by microorganisms can be performed by inoculating and growing at least one kind of microorganism on a raw material used as a substrate. Inoculation of microorganisms to the substrate can be done by adding microorganisms directly into the substrate, or by adsorbing them on a carrier such as alginic acid, polyvinyl, gelatin, etc., for example, in the form of fine beads composed of microorganisms and carrier. Further, it can be used by being fixed to the tube wall of the bioreactor. Fermentation or metabolic conversion by microorganisms is not particularly defined as a microorganism to be used, but can generally be defined as microorganisms other than pathogenic microorganisms that exhibit significant toxicity to living bodies. Examples of microorganisms to be used include microorganisms classified into yeasts: Aciculoconidium, Actonia, Aessosporon, Ambrosiozyma, Amphierna, Anthomyces, Apiotrichum, Arthroascus, Arxula, Ascotrichosporon, Ashbia, Ashbya Genus, Asporomyces, Atelosaccharomyces, Azymocandida, Azymohansenula, Azymomyces, Azymoprocandida, Babjevia, Ballistosporomyces, Basidiotrichosporon, Bensingtonia, Blastobotrysbota, Blastodlastrzo Brettanomyces (Brettanomyces bruxellensis, Brettanomyces anomalus, etc.), Bullera, Bulleromyces, Candida (Candida albicans, Candida amylolenta, Candida anomala, Candida boidinii, Candida entomaea, Candida etchellsment, Candida etchellsii, Candida etchellsment Candida intermedia, Candida krusei, Candida lactosa, Candida lipolytica, Candida mogii, Candida parapsilosis, Candida sake, Candida tropicalis, Candida versatilis, Candida vulgaris, etc., Castellania, Chlamydozyma, Chromotorula, Citeromyces, Cladosporium, Clavispora, Crebrothecium, delbaryo, genus halotolerans, Debaryomyces hansenii, etc.), Debaryozyma, Dekkera, Dekkeromyces, Dematium, Dipodascus, Eeniella, Enantiothamnus, Endoblastoderma, Endoblastomyces, Endomyces, Endomycopsis, Endyllium, Etelexium, Entelex Genus, Eutorula, Eutorulopsis, Fabospora, Fellomyces, Fermentotrichon, Filobasidium, Galactomyces, Geotrichoides, Geotrichum, Guilliermondella, Hanseniaspora, Hansenulaan, Hansenulaan, Hansenulaan, Hansenula Hansenula wickerhamii), Hypomyces, Issatchenkia, Kloeckera (Kloeckera brevis, Klo) eckera fluorescens, Kloeckera japonica, etc.), Kloeckeraspora, Kluyveromyces (Kluyveromyces bulgaricus, Kluyveromyces marxianus, Kluyveromyces thermotolerans, Genus Kockovaella, Kurtzmanomyces, Leucosporidium, Leucosporidium, Leucosporidium Monospora, Monosporella, Mrakia, Myceloblastanon, Mycocandida, Mycoderma, Mycotorula, Mycokluyveria, Mycotoruloides, Myxozyma, Nadsonia, Nectaromyces, Nematospora, Otosporomyces, Ogataea, Ogataea , Oosporidium genus, Pachysolen genus, Parasaccharomyces genus, Paratorulopsis genus, Parendomyces genus, Petasosospora genus, Pichia genus (genus Pichia amylophila, Pichia farinosa, Pichia guilliermondii, Pichia membranifaciens, Pichia mogirum, genus Proticcpo Proteomyces, Pseudohansenula, Pseudomonilia, Pseudomycoderma, Pseudosaccharomyces , Pseudozyma spp, Rhodomyces genus, Rhodosporidium genus, Rhodotorula genus, Saccharomyces genus (Saccharomyces aceti, Saccharomyces cerasi, Saccharomyces cerevisiae, Saccharomyces exiguus, Saccharomyces unisporus, Saccharomyces fibuligera etc.), Saccharomycodes genus, Saccharomycopsis spp, Saturnispora genus, Schizoblastosporion spp, Schizosaccharomyces spp , Schwanniomyces genus, Selenotila genus, Selenozyma genus, Smithiozyma genus, Sporidiobolus sp Genus, Vanrija, Waltomyces, Willia, Willopsis, Wingea, Xanthophyllomyces, Yamadazyma, Zendera, Zygofabospora, Zygopichia, Zygohansenula, Zygorenospora, Zygosaccharomyces, Zygosaccharomyces, etc. . Microorganisms classified as bacteria include Acetobacter genus (Acetobacter aceti, etc.), Achromobacter genus, Acidianus genus, Acidobacterium genus, Acidithiobacillus genus, Acrocarpospora genus, Actinoalloteichus genus, Actinocorallia genus, Actinokineospora genus, Actinomadspura genus, Actinomadspura Actinosynnema genus, Aerococcus genus, Aeromicrobium genus, Agrobacterium genus, Agromyces genus, Ahrensia genus, Alcaligenes genus, Alicyclobacillus genus, Alloiococcus spp. , Aureobacterium genus, Azotobacter genus, Bacillus genus (Bacillus brevis, Bacillus subtilis etc.), Bacteroides genus, Beneckea genus, Bifidobacterium genus (Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis etc.), Brachybacterium genus, Brevicillus, Brevundimonas, Burkholderia, Carnobacterium, Catellat genus ospora, Cellulomonas, Chainia, Chromobacterium, Chryseobacterium, Citrobacter, Clavibacter, Corynebacterium, Couchioplanes, Cryptosporangium, Curtobacterium, Dactylosporangium, Deinococcus, Delftia, Dermatia, Dermatia , Elytrosporangium, Enterobacter, Erwinia, Escherichia, Eubacterium, Excellospora, Exiguobacterium, Faenia, Flammeovirga, Flavobacterium, Flexibacter, Geodermatophilus, Globicatella, Gluconacetobaceto, Gluconacetobacter Genus, Gordonia, Halobacterium, Halococcus, Herbidospora, Hydrogenophilus, Hyphomicrobium, Hyphomonas, Intrasporangium, Janibacter, Jonesia, Kibdelosporangium, Kineopocusato, Kitasposatos, Kitasposatos, Kitasposatos Klebsiella, Kocuria, Kurthia, Lactobacillus (Lactobacillus rimae, Lactobacillus dive rgens, Lactobacillus carnis, Lactobacillus piscicola, Lactobacillus acidophilus, Lactobacillus amylophilus, Lactobacillus animalis, Lactobacillus brevis, Lactobacillus casei, Lactobacillus curvatus, Lactobacillus bulgaricus, Lactobacillus delbrueckii, Lactobacillus fermentum, Lactobacillus fructivorans, Lactobacillus fructosus, Lactobacillus helveticus, Lactobacillus hilgardii, Lactobacillus homohiochii, Lactobacillus kefiri, Lactobacillus malefermentans, Lactobacillus murinus, Lactobacillus paracasei, Lactobacillus paracasei subsp. tolerans, Lactobacillus parakefiri, Lactobacillus pentosus, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus sakei, Lactobacillus confusus, Lactobacillus viridescens, Lactobacillus johnsonii, Lactobacillus viscosus, Lactobacillus bunchneri , Lactobacillus fermentatae, Lactobacillus acidophil-aerogenes, Lactobacillus leichmannii, Lactobacillus gasseri, Lactobacillus bifidus, Lactobaci llus jugurt, Lactobacillus caucasicus, Lactobacillus arabinosus, Lactobacillus kunkeei, Lactobacillus nagelii, Lactobacillus fornicalis, Lactobacillus pentoaceticus, Lactobacillus xylosus, Lactobacillus minutus, etc.), Leuconostoc genus (Leuconostoc lactis, Leuconostoc dextranicum, Leuconostoc mesenteroides, Leuconostoc oenos, Leuconostoc paramesenteroides, Leuconostoc cremoris, Leuconostoc citrovorum etc.), Listonella genus, Lucibacterium genus, Luteococcus genus, Magnetospirillum genus, Marinilabilia genus, Marinospirillum spp. Genus, Nocardioides, Nonmuraea, Nonomuria, Oceanospirillum, Ochrobactrum, Oerskovia, Oligella, Paenibacillus, Pediococcus ui, etc.), Pedobacter, Peptococcus, Peptostreptococcus, Pilimelia, Pimelobacter, Planobispora, Planococcus, Planomonospora, Prevotella, Propionibacterium, Proteus, Protomonas, Pseudomonas, Genus, Rathayibacter, Rhizobium, Rhizomonas, Rhodobacter, Rhodococcus, Rhodopseudomonas, Rhodospirillum, Rothia, Rubrobacter, Ruegeria, Saccharomonospora, Siracrothinas, Sporolactobacillus spp., Stenotrophomonas spp., Streptoalloteichus spp., Streptococcus spp. (Streptococcus durans, Streptococcus faecalis, Streptococcus faecium, Streptococcus bovis, Streptococcus equinus, Streptococcus mutans, Streptococcus salivarius, Streptococcus thermophilus, Streptococcus agalactiae, Streptococcus mitis, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus lactis , Streptococcus dysgalactiae, Streptococcus sanguis, Streptococcus acidominimus, Streptococcus avium, Streptococcus uberis, Streptococcus cremoris, Streptococcus diacetilactis, etc. Genus, Thiobacillus genus, Thiomonas genus, Thiosphaera genus, Weissella genus, Xanthobacter genus, Xanthomonas genus, Zymomonas genus and the like. Microorganisms classified as ascomycetes, basidiomycetes or incomplete fungi other than yeast include Allomyces, Amoebidium, Amorphotheca, Arthroderma, Ascoidea, Ascobolus, Ascodesmis, Aspergillus, Aureobasidium, Botryosphaeria , Botryotinia, Brachybasidium, Byssochlamys, Capnodium, Ceratocystis, Ceratomyces, Chaetomium, Chrysella, Chrysocelia, Chytridium, Claviceps, Cochliobolus, Coemansia, Genus Genus, Cyttaria, Dasyspora, Derchslera, Dirchmyces, Dichomyces, Dothidea, Endogone, Entomophthora, Emericella, Eupenicillium, Eurotium, Exobasidium, Gibberella, Glomus, Graphiola, Gymnoascus, Harpella Helicomyces, Hellvella, Hemicarpenteles, Hyphochytrium, Hypocrea, Laboulbenia, Labyrinthula, Leptosphaeria, Leptosphaerulina, Lophodermium, Melanotaenium , Microascus, Microstroma, Medeolaria, Melampsora, Melampsporella, Morchella, Monascus, Monilinia, Monoblephalis, Mycospharella, Nannizzia, Nectria, Neolecta, Neurospora, Nodulosphaeria, Olizadium, Genus, Penicillium, Perenospora, Pestalotiopsis, Phomopsis, Phragmi
diella genus, Pneumocystis genus, Preussia genus, Pleospora genus, Puccinia genus, Pythium genus, Ravenelia genus, Rickia genus, Rhinocladiella genus, Rhizidiomyces genus, Rhizoctonia spp. Sordaria genus, Sporidiobolus genus, Stibella genus, Stigmatomyces genus, Sydowiella genus, Talaromayces genus, Taphrina genus, Thraustochytrium genus, Tolyposporium genus, Trichoglossum genus, Trichoma genus, Ustilago genus, Verticillium genus, Xylaria genus and the like.

  In fermentation or metabolic conversion by microorganisms, in addition to various raw materials such as plant-based materials, animal-based materials, and other natural product-based materials, the growth and metabolism of microorganisms are regulated or activated, and special biosynthesis or degradation pathways are induced. In order to achieve this, various compounds can be added to the raw material. For example, as a carbon source, a sugar or ethane such as glucose, fructose, galactose, sucrose, maltose, mannose, lactose, glycerol, starch, etc. , Hydrocarbons such as methane, propane, butane, formic acid, acetic acid, propionic acid, lauric acid, palmitic acid, fatty acids such as oleic acid, linoleic acid, linolenic acid, etc., nitrogen sources such as ammonium sulfate, ammonium hydrochloride, ammonium phosphate, etc. Ammonium salt, urea, uric acid, amino acids, etc. Vitamins and compounds that contain potassium, calcium, magnesium, sodium, sulfur, phosphorus, chlorine, etc., as well as iron, copper, zinc, cobalt, nickel, boron, manganese, molybdenum, tin, selenium, silicon It is possible to further add compounds contained in the composition such as arsenic, vanadium, chromium and fluorine. In addition, the optimum temperature, oxygen supply amount, pH, pressure, etc. that affect the growth and metabolic activity of various microorganisms can be arbitrarily set according to the characteristics inherent to various microorganisms. Can be arbitrarily set in the range of 10 to 50 ° C., and the pH can be arbitrarily set in the range of 1 to 14.

  In fractionation or purification, generally known techniques can be used as appropriate. In addition to solvent extraction, for example, liquid chromatography (ion exchange chromatography, ion exclusion chromatography, affinity chromatography, gel filtration chromatography, size exclusion chromatography, etc.). Chromatography, hydrophilic adsorption chromatography, hydrophobic adsorption chromatography, ligand exchange chromatography, etc.), dialysis with semipermeable membrane, crystallization and recrystallization of components, filter paper, membrane filter, ultra filter, Examples thereof include filtration using activated carbon, a filter aid, and the like, centrifugal separation, and fractional precipitation, which is an application thereof, and density gradient separation methods such as a red zone centrifugal separation method and a density gradient sedimentation equilibrium method.

In the present invention, as other compounds used as additives, specifically, silicic anhydride, magnesium silicate, talc, kaolin, bentonite, hectorite, natural or synthetic smectite, stevensite, mica, mica titanium, bismuth oxychloride , Zirconium oxide, Magnesium oxide, Zinc oxide, Titanium oxide, Calcium carbonate, Magnesium carbonate, Yellow iron oxide, Bengala, Black iron oxide, Gunjo, Chromium oxide, Chromium hydroxide, Carbon black, Calamine and other inorganic pigments, Peroxide Hydrogen water, sodium persulfate, ammonium persulfate, sodium perborate, urea peroxide, sodium percarbonate, sodium peroxide tripolyphosphate, sodium bromate, potassium bromate, sodium pyrophosphate, sodium orthophosphate, silica Acid Inorganic reducing agents such as lithium hydrogen peroxide adduct, sodium sulfate hydrogen peroxide adduct, sodium chloride hydrogen peroxide adduct, β-tyrosinase enzyme solution, mushroom extract, strontium sulfate, sodium sulfide, barium sulfide, calcium sulfide , Redox agents such as thioglycolic acid or its salts (calcium thioglycolate, sodium thioglycolate, lithium thioglycolate, magnesium thioglycolate, strontium thioglycolate), 5-aminoorthocresol, 2-amino-4 -Nitrophenol, 2-amino-5-nitrophenol, 1-amino-4-methylaminoanthraquinone, 3,3'-iminodiphenol, 2,4-diaminophenoxyethanol hydrochloride, 2,4-diaminophenol hydrochloride, toluene hydrochloride -2,5-diamine, nitroparaphenylenediamine hydrochloride , Paraphenylenediamine hydrochloride, N-phenylparaphenylenediamine hydrochloride, metaphenylenediamine hydrochloride, orthoaminophenol, N-phenylparaphenylenediamine acetate, 1,4-diaminoanthraquinone, 2,6-diaminopyridine, 1,5-dihydroxy Naphthalene, toluene-2,5-diamine, toluene-3,4-diamine, nitroparaphenylenediamine, paraaminophenol, paranitroorthophenylenediamine, paraphenylenediamine, paramethylaminophenol, picramic acid, sodium picrate, N, N'-bis (4-aminophenyl) -2,5-diamino-1,4-quinonediimine, 5- (2-hydroxyethylamino) -2-methylphenol, N-phenylparaphenylenediamine, metaaminophenol, meta Phenylenediamine, 5-aminoorcresol sulfate , 2-amino-5-nitrophenol sulfate, orthoaminophenol sulfate, orthochloroparaphenylenediamine sulfate, 4,4'-diaminodiphenylamine sulfate, 2,4-diaminophenol sulfate, toluene-2,5-diamine sulfate, sulfuric acid Nitroparaphenylenediamine, paraaminophenol sulfate, paranitroorthophenylenediamine sulfate, paranitrometaphenylenediamine sulfate, paraphenylenediamine sulfate, paramethylaminophenol sulfate, metaaminophenol sulfate, metaphenylenediamine, catechol, diphenylamine, α- Natural dyes such as naphthol, hydroquinone, phloroglucin, sodium 2-hydroxy-5-nitro-2 ', 4'-diaminoazobenzene-5'-sulfonate, hematein, musk, civet, castrium, ambergris Physical Flavor, Anise Essential Oil, Angelica Essential Oil, Ylang Ylang Essential Oil, Iris Essential Oil, Fennel Essential Oil, Orange Essential Oil, Kananga Essential Oil, Caraway Essential Oil, Cardamom Essential Oil, Guayak Wood Essential Oil, Cumin Essential Oil, Black Letter Essential Oil, Cinnamon Essential Oil, Cinnamon Essential Oil, Geranium Essential Oil, Copaiba balsam essential oil, coriandel essential oil, perilla essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, gingergrass essential oil, cedar essential oil, spearmint essential oil, western peppermint essential oil, dairy perfume essential oil, tuberose essential oil, clove essential oil, orange flower essential oil, winter green Essential Oil, Truval Sam Essential Oil, Baturi Essential Oil, Rose Essential Oil, Palmarosa Essential Oil, Persimmon Essential Oil, Hiba Essential Oil, Sandalwood Essential Oil, Petit Glen Essential Oil, Bay Essential Oil, Vetiva Essential Oil, Bergamot Essential Oil, Peruvian Balsam Essential Oil, Boadrose Essential Oil, Haruka Essential Oil, Mandarin Essential , Eucalyptus essential oil, Lime essential oil, Lavender essential oil, Linaroe essential oil, Lemongrass essential oil, Lemon essential oil, Rosemary essential oil, Japanese mint mint essential oil and other plant flavors, other synthetic flavors, 5-amino-o-cresol, o -Aminophenol, m-aminophenol, p-aminophenol, 2,6-diaminopyridine, 5- (2-hydroxylethylamino) -2-methylphenol, N, N-bis (β-hydroxyl) -p-phenylene Diamine / sulfate, N, N-bis (2-hydroxyethyl) -p-phenylenediamine, p-nitro-o-phenylenediamine, p-phenylenediamine, m-phenylenediamine, N-phenyl-p-phenylenediamine, 2-hydroxy-5-nitro-2 ', 4'-diaminoazobenzene / sodium sulfate, toluene-2,5-diamine, 2- (2'-hydroxyethylamino) -5-aminotoluene, N, N-bis ( β-hydroxyl) -p-fu Nylenediamine, N, N-bis (2-hydroxyethyl) -p-phenylenediamine sulfate, 5-amino-o-cresol sulfate, p-aminophenol sulfate, o-chloro-p-phenylenediamine Sulfate, 2- (2'-hydroxyethylamino) -5-aminotoluene, sulfate, 4,4'-diaminodiphenylamine, sulfate, p-methylaminophenol, sulfate, p-phenylenediamine, sulfate, m-phenylenediamine sulfate, toluene-2,5-diamine sulfate, 2,4-diaminophenoxyethanol hydrochloride, toluene-2,5-diamine hydrochloride, m-phenylenediamine hydrochloride, 2, 4-diaminophenol hydrochloride, 3,3'-iminodiphenol, p-phenylenediamine hydrochloride, N-phenyl-p-phenylenediamine hydrochloride, N-phenyl-p-phenylenediamine acetate 1 , 5-dihydroxynaphthalene, Ruen-3,4-diamine, p-methylaminophenol, N, N'-bis (4-aminophenyl) -2,5-diamino-1,4-quinonediimine, o-aminophenol sulfate, 2,4 -Diaminophenol sulfate, m-aminophenol sulfate, 2-amino-4-nitrophenol, 2-amino-5-nitrophenol, 1-amino-4-methylaminoanthraquinone, nitro-p-phenylenediamine Hydrochloride, 1,4-diaminoanthraquinone, nitro-p-phenylenediamine, picramic acid, sodium picramate, 2-amino-5-nitrophenol / sulfate, resorcinol, nitro-p-phenylenediamine / sulfate, p- Nitro-o-phenylenediamine sulfate, p-nitro-m-phenylenediamine sulfate, red No. 2, red No. 3, red No. 102, red No. 104 (1), red No. 105 (1), Red No. 106, Red No. 201, Color 227, Red 230 (1), Red 230 (2), Red 231, Red 232, Red 401, Red 502, Red 503, Red 504, Red 506, Yellow 4 No. 5, Yellow No. 5, Yellow No. 202 (1), Yellow No. 202 (2), Yellow No. 203, Yellow No. 402, Yellow No. 403 (1), Yellow No. 406, Yellow No. 407, Orange No. 205, Orange No. 207, Orange No. 402, Green No. 3, Green No. 204, Green No. 205, Green No. 401, Green No. 402, Brown No. 201, Purple No. 401, Blue No. 1, Blue No. 2, Blue No. 202, Blue 203 No., Blue No. 205, Black No. 401, Red Cabbage Dye, Red Rice Dye, Akane Dye, Anato Dye, Ikumi Dye, Turmeric Dye, Enju Dye, Krill Dye, Amber Dye, Caramel, Gold, Silver, Gardenia Dye, Corn Dye , Onion pigment, onion Dyes, spirulina dyes, buckwheat whole plant dyes, cherry dyes, laver dyes, hibiscus dyes, grape juice dyes, marigold dyes, purple potato dyes, purple yam dyes, lacquer dyes, rutin dyes and coloring agents, avocado oil, Almond oil, fennel oil, sesame oil, olive oil, orange oil, orange raffer oil, sesame oil, cacao butter, chamomile oil, carrot oil, cucumber oil, beef tallow fatty acid, cucumber nut oil, safflower oil, shea fat, liquid shea fat, large Bean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, palm oil, palm kernel oil, owl, coconut oil, beef tallow, lard Oils such as hydrogenated products (hardened oil, etc.), beeswax, carnauba wax, whale wax, lanolin, liquid lano Phosphorus, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax, rice wax, waxes such as squalene, squalane, pristane, mineral oils such as liquid paraffin, petrolatum, paraffin, ozokelide, ceresin, microcristane wax, lauric acid, myristin Acids, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, natural fatty acids such as 12-hydroxystearic acid, undecylenic acid, tall oil, lanolin fatty acid, isononanoic acid, capron Acids, fatty acids such as 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid, isopentanoic acid and the like, synthetic fatty acids, ethanol, isopyropanol, lauryl alcohol, cetanol, Natural alcohols such as teal alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterol, phenoxyethanol, alcohols such as synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, 2-octyldodecanol, isopropyl myristate, isopropyl palmitate, Butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyl decyl dimethyloctanoate, diisobutyl adipate, 2-hexyldecyl adipate, diheptyl undecyl adipate, monoisostearate Acid N-alkyl glycol, isocetyl isostearate, trimethylolpropane triisostearate, diethylhexyl Ethylene glycol sanate, neopentyl glycol diethylhexanoate, cetyl 2-ethylhexanoate, trimethylolpropane triethylhexanoate, pentaerythritol tetraethylhexanoate, cetyl octanoate, octyldodecyl gum, cetyl lactate, myristyl lactate, diethyl phthalate, Esters such as dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate , Metal soaps such as zinc laurate and zinc undecylenate, anionic surfactants (alkyl carboxylates, alkyls Honates, alkyl sulfates, alkyl phosphates), alkyl sulfates (sodium lauryl sulfate, potassium lauryl sulfate, triethanolamine lauryl sulfate, ammonium lauryl sulfate, sodium cetyl sulfate, sodium stearyl sulfate, etc.), secondary Alcohol sulfate ester salt, alkyl ether sulfate ester salt (for example, polyoxyethylene lauryl sulfate triethanolamine, polyoxyethylene lauryl sodium sulfate, etc.), alkyl and alkyl allyl ether sulfate ester salt (N-acylmethylalanine salt, N-acyl) Glutamate, N-acylmethyl taurate, N-acyl isethionate, N-acyl glycine, alkyl phosphate, alkyl ether carboxylate, alkyl sulfonate, alkyl Killsulfosuccinate, sodium polyoxyethylene lauryl ether sulfate, polyoxyethylene lauryl ether sulfate triethanolamine, polyoxyethylene lauryl ether ammonium sulfate, polyoxyethylene alkyl ether sodium sulfate, polyoxyethylene alkyl ether sulfate triethanolamine, polyoxy Ethylene alkyl ether sulfate diethanolamine, polyoxyethylene alkyl ether ammonium sulfate, etc.), higher fatty acid alkylolamide sulfate ester salt, higher fatty acid ester sulfate ester salt (hardened coconut oil fatty acid sodium glyceryl sulfate, etc.), polyoxyethylene alkyl ether carboxylic acid, poly Oxyethylene alkyl allyl ether carboxylates, sulfated oils such as sulfated castor oil, Dialkyl or alkenyl phosphate salts, polyoxyethylene mono or dialkyl or and alkenyl
Acid ester salt (sodium monolauryl phosphate, sodium isostearyl phosphate, arginine 2-hexyldecyl phosphate, potassium 2-heptylundecyl phosphate, polyoxyethylene (4-10) sodium lauryl ether phosphate, sodium monocetyl phosphate Arginine monomyristyl phosphate, sodium monooleyl phosphate, polyoxyethylene (2-10) potassium lauryl ether, sodium dioctyl phosphate, etc.), polyoxyethylene alkyl ether phosphate ester salt (polyoxyethylene lauryl ether) Phosphoric acid, polyoxyethylene oleyl ether phosphoric acid, polyoxyethylene cetyl ether phosphoric acid, polyoxyethylene stearyl ether phosphoric acid, polyoxyethylene alkyl ether phosphoric acid, poly Xyethylene alkylphenyl ether phosphate, etc.), sulfonates of higher fatty acid amides or sulfonates of higher fatty acid esters (α-olefin sulfonate, N-myristoyl-N-methyltaurine sodium, coconut oil fatty acid methyltaurine sodium, Sodium lauroylmethyl taurate, etc.), alkylbenzene sulfonate (dodecylbenzenesulfonic acid, monoethanolamine dodecylbenzenesulfonate, diethanolamine dodecylbenzenesulfonate, triethanolamine dodecylbenzenesulfonate, sodium dodecylbenzenesulfonate, etc.), sulfosuccinate (Sodium diethylhexyl sulfosuccinate, sodium sulfosuccinate, disodium lauryl sulfosuccinate, polyoxyethylene sulfosuccinate Disodium acid, disodium lauryl polyoxyethylene sulfosuccinate, disodium polyoxyethylene lauroyl ethanolamide ester sulfosuccinate, disodium undecylenoylamide ethylsulfosuccinate, monolauroyl monoethanolamide sodium polyoxyethylene sulfosuccinate, lauryl polypropylene glycol Sodium sulfosuccinate, etc.), N-acyl sarcosine salts (such as sodium lauroyl sarcosine, palmitoyl sarcosine sodium), condensates of higher fatty acids and amino acids (N-acyl glutamate, sodium N-stearoyl glutamate, potassium N-palmitoyl glutamate, N- Lauroyl-L-glutamate sodium, N-stearoyl-L-glutamate disodium, -Sodium myristoyl-L-glutamate, sodium myristoyl methyl taurate, sodium palmitoyl methyl taurine, sodium stearoyl methyl taurine, N-palmitoyl-β-alanine arginine, N-palmitoyl aspartate ditriethanolamine, etc.), oleate, suaraic acid Anionic surfactants such as fatty acid soaps such as salts, laurates and palmitates (examples of anionic surfactants include alkali metal salts such as sodium salts and potassium salts, monoethanolamine salts and diethanolamine salts) , Quaternary ammonium salts (alkyltrimethylammonium chloride, cetyl chloride, etc.), organic ammonium salts such as triethanolamine salt, L-lysine salt, L-arginine salt and the like, and ammonium salts. Ammonium, cetyl ammonium bromide, lauryl ammonium chloride, lauryl ammonium bromide, stearyl ammonium chloride, stearyl ammonium bromide, cetyl dimethyl ammonium chloride, cetyl dimethyl ammonium bromide, lauryl dimethyl ammonium chloride, stearyl dimethyl ammonium chloride, lauryl trimethyl ammonium chloride , Lauryl trimethyl ammonium bromide, stearyl dimethyl cetyl ditallow dimethyl ammonium chloride, dicetyl ammonium chloride, dicetyl ammonium bromide, dilauryl ammonium chloride, dilauryl ammonium bromide, distearyl ammonium chloride, distearyl ammonium bromide, chloride Dicetylmethylammonium, dicetylmethylammonium bromide, dilaurylmethylan chloride Nium, dilaurylmethylammonium bromide, distearylmethylammonium chloride, distearylmethylammonium bromide, cetyltrimethylammonium chloride, cetyltrimethylammonium bromide, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, lauryltrimethylammonium bromide, Dialkyldimethylammonium chloride, dicetyldimethylammonium chloride, distearyldimethylammonium chloride, dicocoyldimethylammonium chloride, myristyldimethylbenzylammonium chloride, stearyldimethylbenzylammonium chloride, ethyl lanolin sulfate fatty acid aminopropylethyldimethylammonium chloride, cetyltrimethylammonium chloride, Stearyltrimethylammonium chloride, Behenyltrimethylammonium chloride, behenyldimethylhydroxyethylammonium chloride, stearyldimethylbenzylammonium chloride, distearyldimethylammonium chloride, distearoylethylhydroxyethylmonium metasulfate, dicocoylethylhydroxyethylmonium metasulfate, dipalmitoylethylhydroxyethylmonium metasulfate , And cetyltriethylammonium methylsulfate, alkyltrimethylammonium chloride, alkyldimethylbenzylammonium chloride, dialkyldimethylammonium chloride, alkyltrimethylammonium bromide, alkylpentaethoxyammonium chloride, ditallowdimethylammonium chloride, ditallowdimethylammonium methylsulfate , Ammonium ditallow dipropyl phosphate, ditallow dimethyl ammonium nitrate, di (coconut alkyl) dimethyl ammonium chloride, di (coconut alkyl) dimethyl ammonium bromide, coconut ammonium chloride, stearamide propyl chloride PG-dimonium phosphate, steer Luamidopropylethyldimonium esosulphate, stearamidepropyldimethyl (myristyl acetate) ammonium chloride, stearamidepropyldimethylcetearylammonium tosylate, stearamidepropyldimethylammonium chloride, stearamidepropyldimethylammonium lactate, ethyl sulfate Lanolin fatty acid aminopropylethyldimethylammonium, cationized cellulose, acyl diethylaminoethyl acetate , Acyldimethylaminopropylamide, polyoxyethylene fatty acid amide, myristyldimethylamine oxide, N-lauryldimethylaminoacetic acid betaine, N-myristyldimethylaminoacetic acid betaine, N-stearyldimethylaminoacetic acid betaine, etc.), bis fatty acid ester salt ( Hydroxypropyl-bis-lauric acid amidopropyl-N, N-dimethylammonium chloride, hydroxypropyl-bis-myristic acid amidopropyl-N, N-dimethylammonium chloride, hydroxypropyl-bis-palmitic acid amidopropyl-N, N- Dimethylammonium chloride, hydroxypropyl-bis-stearic acid amidopropyl-N, N-dimethylammonium chloride, hydroxypropyl-bis-behenic acid Midopropyl-N, N-dimethylammonium chloride, hydroxypropyl-bis-oleic acid amidopropyl-N, N-dimethylammonium chloride, hydroxypropyl-bis-isostearic acid amidopropyl-N, N-dimethylammonium chloride, hydroxypropyl-bis -Palm fatty acid amidopropyl-N, N-dimethylammonium chloride, hydroxypropyl-bis-palm fatty acid amidopropyl-N, N-dimethylammonium chloride, hydroxypropyl-bis-tallow fatty acid amidopropyl-N, N-dimethylammonium chloride, Hydroxypropyl-bis-lauric acid amidoethyl-N, N-diethylammonium chloride, hydroxypropyl-bis-myristic acid amidoethyl-N N-diethylammonium chloride, hydroxypropyl-bis-palmitic acid amidoethyl-N, N-diethylammonium chloride, hydroxypropyl-bis-stearic acid amidoethyl-N, N-diethylammonium chloride, hydroxypropyl-bis-behenic acid amidoethyl- N, N-diethylammonium chloride, hydroxypropyl-bis-oleic acid amidoethyl ammonium chloride, hydroxypropyl-bis-isostearic acid amidoethyl-N, N-diethylammonium chloride, hydroxypropyl-bis-coconut fatty acid amidoethyl-N, N- Diethylammonium chloride, hydroxypropyl-bis-palm fatty acid amidoethyl-N, N-diethylammonium chloride, hydro Cypropyl-bis-tallow fatty acid amidoethyl-N, N-diethylammonium chloride, hydroxypropyl-bis-lauric acid amidopropyl-N, N-diethylammonium chloride, hydroxypropyl-bis-myristic amidopropyl-N, N-diethylammonium Chloride, hydroxypropyl-bis-palmitate amidopropyl-N, N-diethylammonium chloride, hydroxypropyl-bis-amidopropyl stearate-N, N-diethylammonium chloride, hydroxypropyl-bis-behenate amidopropyl-N, N-diethylammonium chloride, hydroxypropyl-bis-oleic acid amidopropyl-N, N-diethylammonium chloride, hydroxypropyl-bis- Sostearic acid amidopropyl-N, N-diethylammonium chloride, hydroxypropyl-bis-coconut fatty acid amidopropyl-N, N-diethylammonium chloride, hydroxypropyl-bis-palm fatty acid amidopropyl-N, N-diethylammonium chloride, Hydroxypropyl-bis-tallow fatty acid amidopropyl-N, N-diethylammonium chloride, etc.), stearamidepropyl PG-dimonium chloride phosphate, behenamidopropyl PG dimonium chloride, stearamidepropylethyldimonium ethosulphate, stear Luamidopropyldimethyl (myristyl acetate) ammonium chloride, stearamidepropyldimethylcetearylammonium tosylate, stearamidepropyldi Cationic surfactants such as methylammonium chloride and stearamidepropyldimethylammonium lactate, glycerin fatty acid esters (glyceryl monoundecylenate, glyceryl diundecylenate, glyceryl monomyristate, glyceryl dimyristate, glyceryl monopalmitate, diester Glyceryl palmitate, glyceryl monostearate, glyceryl distearate, glyceryl monooleate, mono-cotton oil fatty acid glycerin, glyceryl monoerucate, glyceryl sesquioleate, glyceryl monostearate, α, α'-glycolic acid pyroglutamate, monostearate Acid glycerin malic acid, etc.), polyglycerin fatty acid ester (diglyceryl monomyristic acid, diglyceryl dimyristic acid, trimyristic acid) Glyceryl, diglyceryl monopalmitate, diglyceryl dipalmitate, diglyceryl tripalmitate, diglyceryl monostearate, diglyceryl distearate, diglyceryl tristearate, diglyceryl monooleate, diglyceryl dioleate, triolein Diglyceryl acid, tetraglyceryl monopalmitate, tetraglyceryl dipalmitate, tetraglyceryl tripalmitate, tetraglyceryl tetrapalmitate, tetraglyceryl pentapalmitate, tetraglyceryl monostearate, tetraglyceryl distearate, tetraglyceryl tristearate , Tetraglyceryl tetrastearate, tetraglyceryl pentastearate, tetraglyceryl monooleate, tetraoleic acid tetra Riseriru trioleate tetraglyceryl, tetraoleate tetraglyceryl, penta oleate tetraglyceryl monopalmitate hexaglyceryl dipalmitate hexaglyceryl, hexaglyceryl tripalmitate, Tetoraparumichin acid Hekisaguri
Seryl, hexaglyceryl pentapalmitate, hexaglyceryl monostearate, hexaglyceryl distearate, hexaglyceryl tristearate, hexaglyceryl tetrastearate, hexaglyceryl pentastearate, hexaglyceryl monooleate, hexaglyceryl dioleate, triolein Hexaglyceryl acid, hexaglyceryl tetraoleate, hexaglyceryl pentaoleate, decaglyceryl monopalmitate, decaglyceryl dipalmitate, decaglyceryl tripalmitate, decaglyceryl tetrapalmitate, decaglyceryl pentapalmitate, decaglyceryl hexapalmitate Glyceryl, decaglyceryl heptapalmitate, decaglyceryl octapalmitate, decagli nonapalmitate Ril, decaglyceryl decapalmitate, decaglyceryl monostearate, decaglyceryl distearate, decaglyceryl tristearate, decaglyceryl tetrastearate, decaglyceryl pentastearate, decaglyceryl hexastearate, decaglyceryl heptearate, octa Decaglyceryl stearate, decaglyceryl nonastearate, decaglyceryl decastearate, decaglyceryl monooleate, decaglyceryl dioleate, decaglyceryl trioleate, decaglyceryl tetraoleate, decaglyceryl pentaoleate, decaglyceryl hexaoleate Glyceryl, decaglyceryl heptaoleate, decaglyceryl octaoleate, decaglyceryl nonaoleate, decagreate decag Seryl, monohydroxystearic acid decaglyceryl, dihydroxystearic acid decaglyceryl, trihydroxystearic acid decaglyceryl, tetrahydroxystearic acid decaglyceryl, pentahydroxystearic acid decaglyceryl, hexahydroxystearic acid decaglyceryl, heptahydroxystearic acid decaglyceryl, Decaglyceryl octahydroxystearate, decaglyceryl nonahydroxystearate, decaglyceryl decahydroxystearate, hexaglyceryl polyricinoleate, decaglyceryl polyricinoleate, polyoxyethylene glyceryl monostearate, polyoxyethylene glyceryl distearate, monoolein Acid polyoxyethylene glycerin, monomyristic acid polyoxyethylene Lenglycerin, etc.), polyoxyethylene glycerin fatty acid ester (polyoxyethylene glycerin monostearate, polyoxyethylene glycerin monoisostearate, polyoxyethylene glycerin triisostearate, etc.), sorbitan fatty acid ester (sorbitan monolaurate, monoolein) Sorbitan acid, sorbitan sesquioleate, sorbitan trioleate, sorbitan monopalmitate, sorbitan monostearate, sorbitan distearate, sorbitan dioleate, sorbitan monopalmitate, sorbitan tristearate, sorbitan trioleate, penta-2- Diglycerol sorbitan ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate, polyoxy monooleate Tylene sorbitan, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan pentaoleate, etc., propylene glycol fatty acid ester ( Propylene glycol monooctanoate, propylene glycol monodecanoate, propylene glycol monostearate, etc.), sucrose fatty acid ester (monolauric acid sucrose ester, dilauric acid sucrose ester, monopalmitic acid sucrose ester, dipalmitic acid sucrose ester, Monostearic acid sucrose ester, distearic acid sucrose ester, etc.), dextrin fatty acid ester (such as dextrin palmitate), Zushi oil fatty acid alkanolamide, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil monoisostearate, polyoxyethylene hydrogenated castor oil triisostearate, polyoxyethylene hydrogenated castor oil monopyroglutamic acid Monoisostearic acid diester, polyoxyethylene hydrogenated castor oil maleic acid, polyoxyethylene alkyl ether (alkyl polyglucoside, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene oleyl ether, polyoxy Ethylene lauryl ether, polyoxyethylene-2-octyldecyl ether, polyoxyethylene cholestanol ether, etc.), polyoxye Tylene alkyl phenyl ether (polyoxyethylene nonyl phenyl ether, polyoxyethylene octyl phenyl ether, etc.), polyoxyethylene fatty acid ester (polyethylene glycol monooleate, polyethylene glycol monostearate, polyethylene glycol monolaurate, etc.), lanolin derivatives (poly Oxyethylene lanolin, polyoxyethylene lanolin alcohol, polyoxyethylene sorbitol lanolin, etc.), POE / POP-alkyl ether (POE / POP-cetyl ether, POE / POP-2-decyltetradecyl ether, POE / POP-monobutyl ether), POE / POP-hydrogenated lanolin, POE / POP-glycerin ether, Tetronic, etc.), alkanolamide (coconut oil fat) Nonionic surfactants such as diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, etc., betaine-type amphoteric surfactants (2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethyl) Betaine aminoacetate, undecylcarboxymethoxyethylcarboxymethylimidazolinium betaine sodium, undecylhydroxyethylimidazolinium betaine sodium, undecyl-N-hydroxyethyl-N-carboxymethylimidazolinium betaine, alkyldiaminoethylglycine hydrochloride solution, Stearyl dihydroxyethyl betaine, stearyl dimethylaminoacetic acid betaine, stearyl dimethyl betaine sodium solution, coconut oil alkyl-N-carboxyl Ethyl-N-hydroxyethylimidazolinium betaine sodium, coconut oil alkylbetaine, coconut oil alkyldimethylaminoacetic acid betaine, coconut oil fatty acid amidopropyl betaine, coconut oil fatty acid-N-carboxymethoxyethyl-N-carboxyethylimidazolinium betaine Sodium, N-lauroyl-N'-carboxymethyl-N'-hydroxyethylethylenediamine sodium, N-cocoyl-N'-carboxymethyl-N'-hydroxyethylethylenediamine sodium, lauryldimethylaminoacetic acid hydroxysulfobetaine, coconut oil alkyldimethyl Aminoacetate hydroxysulfobetaine, laurylaminopropionate triethanolamine, β-laurylaminopropionate sodium, laurate amidepropi Dimethylaminoacetic acid betaine, lauric acid amidopropyl dimethylaminoacetic acid hydroxysulfobetaine, coconut oil fatty acid amidopropyl dimethylaminoacetic acid hydroxysulfobetaine, palm oil fatty acid amidopropyldimethylaminoacetic acid hydroxysulfobetaine, coconut oil fatty acid amidopropyl dimethylaminoacetic acid betaine, Palm oil fatty acid amidopropyldimethylaminoacetic acid betaine, lauryl N-carboxymethoxyethyl-N-carboxymethylimidazolinium disodium dodecanoyl sarcosine, lauryl diaminoethylglycine sodium, lauric acid amidopropyl betaine solution, lauryl sulfobetaine, lauryl hydroxysulfo Betaine, 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazoli Umbetaine, Cocodimethylcarboxymethylbetaine, Lauryldimethylcarboxymethylbetaine, Lauryldimethylalphacarboxyethylbetaine, Cetyldimethylcarboxymethylbetaine, Cetyldimethylbetaine, Laurylbis- (2-hydroxyethyl) carboxymethylbetaine, Stearylbis- (2-hydroxy Propyl) carboxymethylbetaine, oleyldimethylgamma-carboxypropylbetaine, laurylbis- (2-hydroxypropyl) alpha-carboxyethylbetaine, cocodimethylsulfopropylbetaine, stearyldimethylsulfopropylbetaine, lauryldimethylsulfoethylbetaine, laurylbis- (2 -Hydroxyethyl) sulfopropyl betaine, Levon 2000 (Sanyo) Kasei), Anon BDF (manufactured by Nippon Oil & Fats), Lonzain-CS (manufactured by Lonza), Miratine CBS (manufactured by Milanol), Anon BL (manufactured by Nippon Oil & Fats), Lonzain 12CS (manufactured by Lonza) Imidazolinium-type amphoteric surfactant (bis (stearyl-N-hydroxyethylimidazoline) chloroacetic acid complex, N-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, N-alkyl-N-carboxymethyl- N-hydroxyethylethylenediamine lauryl sulfate and salts thereof, coconut oil alkyl-N-carboxyethoxyethyl-N-carboxyethyl imidazolinium disodium hydroxide, coconut oil alkyl-N-carboxymethoxyethyl-N-carboxyethyl imidazole Ni disodium hydroxy Palm oil alkyl-N-carboxymethoxyethyl-N-carboxyethylimidazolinium disodium lauryl sulfate, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl- 2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, ovazoline 662 (manufactured by Toho Chemical Co., Ltd.), swanol AM-101 (manufactured by Nikko Chemicals Co., Ltd.), anon GLM (manufactured by NOF Corporation), aminopropion, etc. Acid type amphoteric surfactant (alkylaminopropionic acid such as sodium dodecylaminopropionate, alkylaminodipropionic acid, etc.), sodium dodecylaminopropanesulfonate, N-higher alkylaspartic acid or its salt, coamidopropyl chlorinated polyethylene Recall dimonium phosphate, cocamidopropyl hydroxysultain, sodium lauroyl sarcosinate, alkylamine oxide (decylamine oxide, cocoamine oxide, myristoylamine oxide, palmitoylamine oxide, alkyldimethylamine oxide, alkylamidopropylamine oxide, etc.) Monosaccharide polyhydric alcohols such as amphoteric surfactants, natural surfactants (lecithin, sodium caseinate, sphingolipids, saponins, mannosyl polyhydric alcohol fatty acid esters, glucosyl polyhydric alcohol fatty acid esters, galactosyl polyhydric alcohol fatty acid esters, etc.) Fatty acid esters or disaccharide polyhydric alcohol fatty acid esters, oligosaccharide polyhydric alcohol fatty acid esters, etc.) and amino acid surfactants (capric chloride) , Lauric acid chloride, myristic acid chloride, palmitic acid chloride, stearic acid chloride, oleic acid chloride, behenic acid chloride, coconut oil fatty acid chloride and other fatty acid chlorides and glycine, sarcosine, β-alanine, N-methyl-β-alanine, Reaction products with amino acids such as taurine and N-methyltaurine), silicone surfactants (silicon KF-6011 (manufactured by Shin-Etsu Chemical Co., Ltd.), KF-6012 (manufactured by Shin-Etsu Chemical Co., Ltd.), KF-6013 ( Shin-Etsu Chemical), KF-6015 (Shin-Etsu Chemical), KF-6016 (Shin-Etsu Chemical), KF-6017 (Shin-Etsu Chemical), X-22-4991 (Shin-Etsu Chemical) Manufactured), NUC silicon L7002 (manufactured by Nihon Unicar), SH-3772C (Toray Dow) Corning Silicone), SH-3775C (Toray Dow Corning Silicone) and other polyoxyalkylene-modified organopolysiloxanes, ABIL EM-90 (Gold Schmidt), ABIL B9806 (Gold Schmidt) ,
Recon KF-6026 (manufactured by Shin-Etsu Chemical Co., Ltd.) and other long-chain alkyl-containing polyoxyalkylene-modified organopolysiloxanes), polyether-modified silicones (polyoxyethylene / methylpolysiloxane copolymers, poly (oxyethylene / oxypropylene) ) Methylpolysiloxane copolymer, etc.), oxazoline-modified organopolysiloxane, alkyl-modified organopolysiloxane, styryl ketone silicone derivatives, dimethylpolysiloxane, methylphenylpolysiloxane, epoxy-modified silicone, fluorine-modified silicone, alcohol-modified silicone, alkyl-modified Silicone, alkoxy-modified silicone, amino-modified silicone, ammonium-modified polymer silicone, organopolysiloxane, methylphenylpolysiloxane, polysilos Sun, poly (N-acylalkylenimine) -modified silicone, dimethylpolysiloxane, methylphenylpolysiloxane, nitrogen-containing acrylic-silicone graft copolymer, decamethylcyclopentasiloxane, fluorine-substituted alkyl-modified silicone, organopolysiloxane Silylalkyl-modified silicone, tricyclic diterpenecarboxylic acid-modified silicone, trifluoroalkyl-modified silicone, divinylpolydimethylsiloxane, dihydrogenopolydimethylsiloxane, dihydrogenopolydimethylsiloxane divinylpolydimethylsiloxane polymer, trimethylsiloxysilicic acid, poly Oxypropylene-methylpolysiloxane copolymer, ethylpolysiloxane, ethylmethylpolysiloxane, ethylphenylpolysiloxane, octame Lucyclotetrasiloxane, diorganopolysiloxane, octamethylcyclotetrasiloxane, tetramethyltetraphenyltetracyclosiloxane, polyether-modified polysiloxane, amino-modified polysiloxane, epoxy-modified polysiloxane, fluorine-modified polysiloxane, alcohol-modified Polysiloxane, alkyl-modified polysiloxane, dodecamethylcyclohexasiloxane, laurylmethicone copolyol, aminoethylaminopropylsiloxane / dimethylsiloxane copolymer, silicone compounds such as eugenol-modified silicone, selenium disulfide, alkylisoquinolinium bromide Examples thereof include hair treatment agents such as liquid, zinc pyrithione, biphenamine, thianthol, quinine hydrochloride, and strong aqueous ammonia.

  In addition, hormones, sequestering agents, pH adjusters, chelating agents, antiseptic / antibacterial agents, refreshing agents, stabilizers, emulsifiers, animal / plant proteins and their degradation products, animal / plant polysaccharides and their Degradation products, animal / plant glycoproteins and their degradation products, anti-inflammatory agents, antiallergic agents, wound treatment agents, foaming agents, thickeners, enzymes, purified water (electronic water, small clusters, etc.), deodorant / A deodorant etc. can be used in combination.

  Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Production of diisopropyl squaric acid 4 g (35.1 mmol) of squaric acid (purity 99.9% or more), 20 mL of anhydrous benzene, and 20 mL of anhydrous 2-propanol were added to a reaction vessel (Dean-Stark apparatus), and the mixture was heated to reflux for 1 hour. Thereafter, 10 mL of the solvent was removed from the reaction vessel, and 5 mL of anhydrous benzene and 5 mL of anhydrous 2-propanol were further added. After repeating this operation three times, the reaction solution was cooled to room temperature, 30 mL of ether was added, and the ether layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 5.4 g of diisopropyl squaric acid as the title compound.

Production of Squaric acid-2-phosphate magnesium salt 5.71 g (50 mmol) of squaric acid and 7.91 g (100 mmol) of pyridine were dissolved in 60 mL of pure water. This solution was brought to 15 ° C. or lower, and an aqueous solution obtained by dissolving 20.73 g (150 mmol) of potassium carbonate in 15 mL of pure water and 11.50 g (75 mmol) of phosphorus oxychloride were alternately added dropwise over 1 hour with stirring. After the reaction completion liquid was heated to 90 ° C. and heated for 10 minutes, the reaction liquid was returned to room temperature, and an aqueous solution obtained by dissolving 7.60 g (55 mmol) of potassium carbonate in 10 mL of pure water and 3.83 g (25 mmol) of phosphorus oxychloride were added thereto. The solution was added dropwise alternately over 30 minutes with stirring. This solution was heated at 90 ° C. for 5 minutes as described above. The solution was cooled to room temperature, then Amberlite IRA-68 ^- to remove chlorine (Cl type) squarate unreacted treated with resin, pyridine and by-products. The solution obtained by passing through the resin was concentrated to a volume of 100 mL, neutralized with 3.19 g (55 mmol) of magnesium hydroxide, and the aqueous solution was further concentrated to 30 mL and added with 50 mL of methanol. The milky white crystals were collected by filtration. The milky white crystals thus obtained were recrystallized with 35 mL of water-methanol (1: 2) to obtain 6.06 g of squaric acid-2-phosphate magnesium salt as the title compound.

Production of squaric acid-2-glucopyranoside 5.71 g (50 mmol) of squaric acid and 4.62 g (55 mmol) of sodium bicarbonate were dissolved in 50 mL of DMSO and stirred at room temperature for 10 minutes. Thereto was added 13.4 g (55 mmol) of glucoside bromide, heated to 40 ° C., and stirred for 30 hours. After cooling to room temperature, 50 mL of pure water was added to adjust the pH to 5.5. Next, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dehydrated with sodium sulfate, and concentrated under reduced pressure to obtain white crystals. Next, the obtained white crystals were dissolved in ethyl acetate and purified using silica gel column chromatography (elution solvent was benzene-ethyl acetate 2: 1 mixture) to give 11.2 g of squaric acid-2-glucopyranoside as the title compound. Obtained.

Production of squaaryl dipalmitate 5.71 g (50 mmol) of squaric acid and 9.24 g (110 mmol) of sodium bicarbonate were dissolved in 80 mL of DMSO and stirred at room temperature for 15 minutes. Thereto was added 30.2 g of palmitic bromide (110 mmol), and the mixture was heated to 50 ° C. and stirred for 48 hours. After cooling to room temperature, 50 mL of pure water was added to adjust the pH to 5.0. Next, extraction was performed with ethyl acetate, and the organic layer was washed with saturated brine, dehydrated with sodium sulfate, and concentrated under reduced pressure to obtain an oily substance. Next, the obtained oily substance was dissolved in ethyl acetate and purified using silica gel column chromatography (elution solvent was benzene-ethyl acetate 3: 1 mixture) to obtain 26.9 g of squalyl dipalmitate as the title compound. .

Production of dibenzylsquaric acid After adding 1N-NaOH aqueous solution to 500 mL of 11.4 g (100 mmol) aqueous solution of squaric acid (purity 99.9% or more) until pH 7-8, 34.0 g (200 mmol) of silver nitrate was added at room temperature did. The produced brown silver salt was collected by filtration, washed with water, acetone and ether and dried under reduced pressure. To 200 mL of the obtained washed silver salt ether solution, 48 mL (417 mmol) of benzyl chloride is added and heated to reflux for 2 hours to form a precipitate, and the formed precipitate is filtered off to obtain a filtrate. Obtained. The obtained filtrate was concentrated under reduced pressure to produce white crystals, and recrystallized from n-hexane to obtain 13.5 g of dibenzyl squaric acid as the title compound.

Production of Squalylaminopropyl Phosphate 34.1 mL (360 mmol) of phosphorus oxychloride was dissolved in 400 mL of dichloromethane, and the resulting solution was cooled to 0 to 5 ° C. to obtain a reaction solution. Next, after 28 mL (360 mmol) of 3-amino-1-propanol and 102 mL (730 mmol) of triethylamine were diluted to 200 mL with dichloromethane, the whole amount of the diluted solution was added dropwise to the reaction solution over 2 hours. After the dropwise addition, the produced trimethylammonium chloride was filtered off to obtain a filtrate. The obtained filtrate was washed with 100 mL of purified water, dried over anhydrous sodium sulfate, and the filtrate obtained by filtration was concentrated to dryness under reduced pressure to give 2-chlorotetrahydro-1,3,2-oxaaza A phospholine oxide was obtained. Next, 5.24 g (46 mmol) of squaric acid (purity 99.9% or more) was dissolved in 200 mL of chloroform, and then 12.9 mL (96 mmol) of trimethylamine was added dropwise in an ice bath at 5 ° C. Next, 8.6 g (55 mmol) of 2-chlorotetrahydro-1,3,2-oxaazaphosphorine oxide was dissolved in 20 mL of chloroform, and this solution was added dropwise to the solution containing squaric acid. After the dropwise addition, the mixture was stirred at room temperature for 24 hours. Next, the organic layer in the mixed solution was washed with a phosphoric acid aqueous solution, and then anhydrous sodium sulfate and activated carbon were added and dried. The filtrate obtained by filtering the mixture was concentrated under reduced pressure, then added to 30 mL of purified water, and stirred at 50 ° C. for 3 hours. 150 mL of isopropanol was added to the filtrate after stirring, and the mixture was concentrated to dryness under reduced pressure to obtain 3.14 g of squalylaminopropyl phosphate as the title compound.

Production of squaric acid-2-α-tocopherol 5.71 g (50 mmol) of squaric acid and 4.62 g (55 mmol) of sodium bicarbonate were dissolved in 50 mL of DMSO and stirred at room temperature for 10 minutes. Thereto was added 27.9 g (55 mmol) of α-tocopherol bromide, warmed to 40 ° C., and stirred for 24 hours. After cooling to room temperature, 50 mL of pure water was added to adjust the pH to 5.0. Next, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain an oily substance. Next, the obtained oily substance was dissolved in ethyl acetate and purified using silica gel column chromatography (elution solvent was benzene-ethyl acetate 3: 1 mixture) to give the title compound, squaric acid-2-α-tocopherol. 20.7 g was obtained.

Production of squaric acid-2-calcium sulfate 5.71 g (50 mmol) of squaric acid and 7.91 g (100 mmol) of pyridine were dissolved in 60 mL of pure water. Next, this solution was adjusted to 15 ° C. or lower, and an aqueous solution in which 20.73 g (150 mmol) of potassium carbonate was dissolved in 100 mL of pure water and 11.90 g (100 mmol) of thionyl chloride were alternately added dropwise over 1 hour with stirring. And reacted. Next, the solution after completion of the reaction was heated at 90 ° C. for 10 minutes. After cooling this solution to room temperature, an aqueous solution prepared by dissolving 7.60 g (55 mmol) of potassium carbonate in 50 mL of pure water and 5.95 g (50 mmol) of thionyl chloride were alternately added dropwise to this solution over 30 minutes while stirring. The solution was then heated at 90 ° C. for 5 minutes and then cooled to room temperature. Next, unreacted compounds and by-products in the solution were removed from this solution using Amberlite IRA-68 (Cl type) resin. Next, the solution was concentrated until the total amount reached 100 mL, neutralized by adding 4.07 g (55 mmol) of calcium hydroxide, and further concentrated until the total amount of the solution reached 30 mL. Next, 30 mL of methanol was added to this solution, and milky white crystals formed were collected by filtration. The obtained milky white crystals were recrystallized with 25 mL of a water-methanol 1: 2 mixture to give the title compound, squaric acid-2- 7.28 g of calcium sulfate was obtained.

Production of 2-aminoethyl squaryl sulfate: 5.71 g (50 mmol) of squaric acid and 4.62 g (55 mmol) of sodium bicarbonate were dissolved in 50 mL of DMSO and stirred at room temperature for 15 minutes. Next, 6.88 g (55 mmol) of taurine bromide was added, and the mixture was heated to 50 ° C. and stirred for 24 hours. After cooling to room temperature, 50 mL of pure water was added to adjust the pH to 5.5. Next, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain milky white crystals. Next, the resulting milky white crystals were dissolved in ethyl acetate and purified using silica gel column chromatography (elution solvent was benzene-ethyl acetate 2: 1 mixed solution) to give 9.01 g of 2-aminoethyl squaryl sulfate as the title compound. Got.

Production of 2-ethyl squaric acid 5.71 g (50 mmol) of squaric acid and 4.62 g (55 mmol) of sodium bicarbonate were dissolved in 50 mL of DMSO and stirred at room temperature for 10 minutes. Next, 5.99 g (55 mmol) of ethyl bromide was added, and the mixture was heated to 50 ° C. and stirred for 20 hours. After cooling to room temperature, 50 mL of pure water was added to adjust the pH to 5.5. Next, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain milky white crystals. Next, the milky white crystals obtained were dissolved in ethyl acetate and purified using silica gel column chromatography (eluent: benzene-ethyl acetate 2: 1 mixture) to give the title compound, 2-ethyl squarate. 4.62 g was obtained.

Production of 2-propyl squaric acid 5.71 g (50 mmol) of squaric acid and 4.62 g (55 mmol) of sodium hydrogen carbonate were dissolved in 50 mL of DMSO and stirred at room temperature for 10 minutes. Next, 6.76 g (55 mmol) of propyl bromide was added, and the mixture was heated to 50 ° C. and stirred for 20 hours. After cooling to room temperature, 50 mL of pure water was added to adjust the pH to 5.5. Next, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain milky white crystals. Next, the milky white crystals obtained are dissolved in ethyl acetate and purified using silica gel column chromatography (elution solvent is benzene-ethyl acetate 2: 1 mixture) to give the title compound 2-propyl squarate. 5.93 g was obtained.

Melanin production inhibition test 1
As samples to be used in this test, diisopropyl squaric acid of Example 1 (hereinafter referred to as diisopropyl squaric acid), squaric acid-2-magnesium phosphate of Example 2 (hereinafter, squaric acid-2-phosphoric acid). Magnesium), squaric acid-2-glucopyranoside of Example 3 (hereinafter referred to as squaric acid-2-glucopyranoside), squaaryl dipalmitate of Example 4 (hereinafter referred to as squalyl dipalmitate), Example 5 Dibenzyl squaric acid (hereinafter referred to as dibenzyl squaric acid), squalylaminopropyl phosphate of Example 6 (hereinafter referred to as squalylaminopropyl phosphate), squaric acid-2- of Example 7 α-tocopherol (hereinafter referred to as squaric acid-2-α-tocopherol) and 10% DMSO aqueous solution of ascorbic acid as positive control . The concentration of each sample with respect to B16 melanoma cells as test cells was adjusted to 2.6 mM. B16 melanoma cells 5 × 10 ⁴ cells 5.0% fetal calf serum (hereinafter FBS) 37 ° C. at MEM containing liquid medium (60 mm dish) were cultured for 24 hours before, the medium was removed. Next, theophylline-containing 5% FBS-containing MEM liquid medium and a sample having the above concentration were added to the pre-cultured B16 melanoma cells and cultured at 37 ° C. for 120 hours. Then, after removing the medium and recovering the cells using Tripsin / EDTA solution, adding ether-ethanol mixture (1: 3), centrifuging at 2000 rpm, and removing the solvent, The contained non-melanin material was removed. Next, the cells were heated at 90 ° C. in 1N NaOH solution containing 10% DMSO to extract melanin in the cells. The absorbance at 420 nm of the obtained melanin extract was measured, and the obtained numerical value was defined in this test as the amount of melanin produced. The results are shown in FIG.

Results of melanin production inhibition test 1 As a result of examining the melanin production inhibitory action of each test sample on B16 melanoma cells, as shown in FIG. 1, as compared with negative control and positive control ascorbic acid, Examples 1 to All the samples consisting of each squaric acid derivative described in 7 showed significantly low melanin production. Therefore, it was found that the product of the present invention has an excellent melanin production inhibitory action.

Melanin production inhibition test 2
Samples to be used in this test include diisopropyl squaric acid, squaric acid-2-magnesium phosphate, squaric acid-2-glucopyranoside, dipalmitic acid squaryl, dibenzyl squaric acid, squalylaminopropyl phosphate, squaric acid -2-α-tocopherol and 88 mM each of 10 mM DMSO aqueous solution of ascorbic acid as a positive control and 10% DMSO aqueous solution as a negative control were used. The outline of this study is the effect of the test substance on the series of processes in which melanin is synthesized and melanocytes are expressed by adding L-DOPA, a substrate for melanin synthesis, in cells that have induced the pathway of melanin biosynthesis. Is to investigate. In this test, a change in the number of melanocytes expressed was used as an index for suppressing or promoting melanin production. C57BL mice (8-week-old male) were irradiated with ultraviolet rays (FL20-SE lamp manufactured by Toshiba Corporation) 15.2 mL / cm ² once a day, and this was continued for 5 days. Next, one week after the last irradiation day, the pinna of the mouse was collected and the cartilage was removed, and then the skin of the outer ear was immersed in a 2N-NaBr solution at 37 ° C. for 2 hours. Next, 1.0 mL of each sample was added to 2 mL of 0.14% L-DOPA solution (0.1 M phosphate buffer, pH 7.2) to prepare a mixed solution. Next, only the epidermis was separated from the immersed outer ear skin, and the obtained epidermis was immersed in the mixed solution at 37 ° C. for 3 hours. Next, the immersed epidermis was stained with melanocytes, and the number of melanocytes within an area of 0.09 mm ² of the epidermis after staining was measured with a microscope at a total of five locations, and the average value was obtained. The results are shown in FIG.

Results of melanin production inhibition test 2 As a result of testing the influence of each test sample on the number of melanocytes expressed, as shown in FIG. A sample composed of an acid derivative significantly reduced the number of melanocyte expression. Therefore, the product of the present invention has an excellent melanocyte expression inhibitory action. In this test, since the change in the number of melanocytes expressed was used as an index of the change in melanin production, it was found that the product of the present invention has an excellent melanin production inhibitory action.

Whitening effect test in humans In this test, a cream containing squaric acid derivatives (squaric acid-2-magnesium phosphate, squalyl dipalmitate, squalylaminopropyl phosphate, and squaric acid-2-α-tocopherol) (in the table) The description is an example), and a cream not containing the above components as a comparison target (the description in the table is a comparative example) was manufactured and used in this test. The test method is applied daily to women aged 20 to 35 years, who are monitors, and the sensory effect on the effect of improving spots and freckles, dullness, and skin black areas such as sunburn after 3 months We decided to investigate the existence of sex. Each manufactured cream was set to 10 people as one group, and one type of cream was continuously applied to one group. The survey results of responses from monitors at the time of 3 months passed are shown in the notation method described below. The results are shown in Table 1.
[Result of answer]
+++: Remarkable effectiveness was felt for the target effect.
++: Effectiveness was felt for the target effect.
+: Some effectiveness was felt for the target effect.
−: Effectiveness was not felt for the target effect.

Results of whitening effect test in humans As a result of testing the whitening effect of each cream on humans, as shown in Table 1, the creams containing each squaric acid derivative were effective in improving spots and freckles compared with the comparison target, and improved dullness. Regarding the effect and the improvement effect of the skin black part such as sunburn, all of them had a remarkable effect of improvement effect. Therefore, it was found that the product of the present invention has an excellent whitening effect on humans.

Antioxidation test using active oxygen scavenging ability as an index In this test, the reaction between reactive oxygen species generated by xanthine-xanthine oxidase oxidation reaction and nitroblue tetrazolium (hereinafter referred to as NBT) was used as an index for the active oxygen scavenging ability. . Samples to be used in this test include diisopropyl squaric acid, squaric acid-2-magnesium phosphate, squaric acid-2-glucopyranoside, squalyl dipalmitate, dibenzyl squaric acid, squalylaminopropyl phosphate and squaric acid. A 0.9% 10% DMSO aqueous solution of -2-α-tocopherol and purified water were used as a negative control. To 2.6 mL of a substrate solution prepared by dissolving xanthine and EDTA to 3.0 mM in 0.05 M sodium carbonate-hydrochloric acid buffer (pH 10.2), 0.1 mL of a 0.75 mM NBT aqueous solution, 0.15% BSA (bovine serum albumin) aqueous solution 0.1 mL and 0.1 mL of the sample were mixed and allowed to stand at 25 ° C. for 10 minutes. Next, 0.1 mL of 20 units / mL milk-derived xanthine oxidase (Roche) aqueous solution was added and reacted at 25 ° C. for 20 minutes, and then 0.1 mL of 6.0 mM cupric chloride aqueous solution was added to stop the reaction. And OD560nm of the obtained reaction liquid was measured. Moreover, the group which inhibited reaction by adding cupric chloride aqueous solution simultaneously with each sample was set as the blank, and the OD560nm was measured. And the NBT reduction suppression rate of each sample was computed from the value of each OD560nm from the following formula 1. The results are shown in FIG.

Results of antioxidation test using active oxygen scavenging ability as an index As a result of examining the NBT reduction inhibition rate of each test sample, as shown in FIG. 3, the samples made of the squaric acid derivatives of Examples 1 to 7 are remarkably high. NBT reduction inhibition rate was shown. Therefore, it was found that the product of the present invention has an excellent active oxygen scavenging action and an excellent antioxidant action based on the active oxygen scavenging ability. The test results suggested that the product of the present invention has an effect of preventing or improving skin aging caused by oxidation involving active oxygen species.

Antioxidation test using lipid peroxidation inhibition ability as an index In this test, peroxidation of linolenic acid induced by ultraviolet rays was used as an index. Samples to be used in this test include diisopropyl squaric acid, squaric acid-2-magnesium phosphate, squaric acid-2-glucopyranoside, dipalmitic acid squaryl, dibenzyl squaric acid, squalylaminopropyl phosphate, squaric acid -2-α-tocopherol and ascorbic acid having an antioxidative effect of 150 mM each in 0.8% aqueous sodium lauryl sulfate solution as a positive control and a 0.8% aqueous sodium lauryl sulfate solution as a negative control were used. Linolenic acid was added to a 0.8 w / v% sodium lauryl sulfate aqueous solution so as to be 0.1% and dissolved. 4.9 mL of this solution was collected in a 9 mL screw bottle, 0.1 mL of a sample was added thereto, and ultraviolet rays (3 FL20-SE lamps and 3 FL20-SB lamps, manufactured by Toshiba Corporation) were irradiated for 1 hour. Next, 1 mL of this solution was added to a centrifuge tube containing 0.02 mL of 4.5% butylhydroxytoluene (BHT), 1.0 mL of 0.67% thiobarbituric acid / 15% acetic acid aqueous solution was further added, and the mixture was heated at 95 ° C. for 1 hour. . After heating, the mixture was cooled to room temperature, 4 mL of 15% methanol-containing n-butanol solution was added, and the mixture was vigorously stirred and then centrifuged at 3000 rpm. Next, an n-butanol layer was collected from the centrifuged solution, and the absorbance at 532 nm of the obtained n-butanol layer was measured. Next, the difference between the absorbance obtained above and the absorbance obtained by performing the same operation in the non-irradiated state using the same sample was calculated, and the obtained value was defined as the amount of lipid peroxidation. And the lipid peroxidation suppression rate of each sample when the lipid peroxidation amount at the time of using a negative control was set to 100 was computed. The results are shown in FIG.

Results of Antioxidation Test Using Lipid Peroxidation Inhibitory Capacity as an Indication Result As a result of examining the lipid peroxidation inhibition rate of each test sample, as shown in FIG. Samples consisting of ~ 7 squaric acid derivatives showed significantly higher lipid peroxidation inhibition rates. Therefore, it was found that the product of the present invention has an excellent lipid peroxidation inhibiting action and an antioxidant action based on lipid peroxidation inhibiting ability as compared with conventional antioxidants. The test results suggested that the product of the present invention has an effect of preventing or improving skin aging caused by the production of lipid peroxide by ultraviolet rays.

Collagen production promotion test Samples to be used in this test include diisopropyl squaric acid, succinic acid-2-magnesium phosphate, squaric acid-2-glucopyranoside, squalyl dipalmitate, dibenzyl squaric acid, squalyl amino phosphate Propyl, squaric acid-2-α-tocopherol, and 0.1 mM each of 10% DMSO aqueous solution of ascorbic acid, which has been confirmed to have collagen production ability, were used as a positive control. Normal human dermal fibroblasts (NR1RGB), so that 3 × 10 ⁵ cells / dish, were seeded in 5.0% fetal bovine serum-containing 5% EagleMEM liquid medium (35mm dish), 37 ℃, of 5% CO ₂ Cultured for 24 hours under conditions. After that, the medium was removed, and then the medium for each sample with 10% sample added to the total volume of the same medium was added to each dish, and cultured for 144 hours at 37 ° C. and 5% CO ₂ . The amount of collagen contained in the culture solution obtained after the culture was measured. At this time, the same operation was performed using a medium supplemented with 10% purified water as a negative control. The amount of collagen in the culture solution was measured using a collagen measurement kit manufactured by BIOCOLOR. After culturing for 144 hours, 200 μL of each culture solution was collected on a 96 wells microplate, 200 μL of a staining reagent was added to each culture solution, and the mixture was gently stirred for 30 minutes to stain collagen. Next, each culture solution was centrifuged at 12000 rpm for 10 min to collect the stained collagen. Next, 200 μL of an alkaline solution (attached to the collagen measurement kit) was added to the collected collagen to extract the pigment staining the collagen. Then, the absorbance at 570 nm of each extract obtained was measured. And the collagen production rate of each sample was calculated from the absorbance of each sample addition group obtained when the amount of collagen in the negative control was set to 100. The results are shown in FIG.

Results of Collagen Production Promotion Test As a result of testing the collagen production promotion effect of each test sample, as shown in FIG. Compared with, the collagen production rate was remarkably high. Therefore, it was found that the product of the present invention has an excellent collagen production promoting action. From the above test results, it was suggested that the product of the present invention has an effect of preventing or improving skin aging caused by collagen loss or reduced collagen production ability.

Collagenase production inhibition test Samples to be tested in this test include diisopropyl squaric acid, squaric acid-2-magnesium phosphate, squaric acid-2-glucopyranoside, dipalmitic acid squalyl, dibenzyl squaric acid, squalyl amino phosphate Propyl and squaric acid-2-α-tocopherol each in 0.88M 10% DMSO aqueous solution and 10% DMSO aqueous solution as a negative control were used. UV light (3 FL20S / BLB lamps and 3 FL20S / E lamps) with a total volume of 4 J / cm ² (36 to 216 mJ / cm ² per dose) 3 times a week on the back of hairless mice (6-week-old females) Irradiated by Toshiba). 100 μL of each sample was applied to each hairless mouse 1 hour before UV irradiation. Five hairless mice were used for one sample, and this was made into one group. A group of non-irradiated ultraviolet rays was also provided. Next, the dorsal skin of each group of hairless mice was collected, punched to a diameter of 1 cm, and then chopped. 1.0 mL of physiological saline was added to the cut skin and homogenized, and centrifuged at 15000 rpm for 15 min to obtain a supernatant. A 1.0 mM collagen aqueous solution (synthetic substrate PZ-peptide 0.5 mg / mL) as a substrate was added to 500 μL of the supernatant and allowed to react at 37 ° C. for 30 minutes. Next, 1.0 mL of 25 mM citric acid solution was added to stop the reaction, 5.0 mL of ethyl acetate was added and stirred, and the ethyl acetate layer was extracted. Next, after centrifugation at 3000 rpm for 5 minutes, the amount of protein contained in the solution is measured using a protein assay system (manufactured by BioRad), the absorbance at a wavelength of 320 nm is measured, and the collagenase specific activity is determined from the obtained absorbance. I asked. Then, the collagenase specific activity in the supernatant in the system to which the sample was added, when the collagenase specific activity in the back skin of hairless mice not irradiated with ultraviolet rays was 1, was calculated. The results are shown in FIG.

Results of Collagenase Production Inhibition Test As a result of examining the collagenase production inhibitory effect of each test sample, as shown in FIG. The sample composed of squalinic acid derivatives significantly suppressed the increase in the specific activity of collagenase. Therefore, it was found that the product of the present invention has an excellent collagenase production inhibitory action. The test results suggested that the product of the present invention has an effect of preventing or improving skin aging caused by activation of MMP production.

Elastase Production Inhibition Test Samples to be tested in this test include diisopropyl squaric acid, squaric acid-2-magnesium phosphate, squaric acid-2-glucopyranoside, dipalmitic acid squalyl, dibenzyl squaric acid, squalyl amino phosphate Propyl and squaric acid-2-α-tocopherol each in 0.88 M 10% DMSO aqueous solution and 10% DMSO aqueous solution as a negative control were used. UV light (3 FL20S / BLB lamps and 3 FL20S / E lamps) with a total volume of 4 J / cm ² (36 to 216 mJ / cm ² per dose) 3 times a week on the back of hairless mice (6-week-old females) Irradiated by Toshiba). 100 μL of each sample was applied to each hairless mouse 1 hour before UV irradiation. Five hairless mice were used for one sample, and this was made into one group. A group of non-irradiated ultraviolet rays was also provided. Next, the dorsal skin of each group of hairless mice was collected, punched to a diameter of 1 cm, and then chopped. 1.0 mL of physiological saline was added to the cut skin and homogenized, and centrifuged at 15000 rpm for 15 min to obtain a supernatant. To 500 μL of this supernatant, 100 μL of 1.0 mM elastin aqueous solution (N-succinyl-Ala-Ala-Ala-p-nitroanilide) as a substrate was added and reacted at 37 ° C. for 30 minutes. The amount of protein contained in the solution was measured using a protein assay system (manufactured by BioRad), the absorbance at a wavelength of 405 nm was measured, and the elastase specific activity was determined from the obtained absorbance. Then, the elastase specific activity in the supernatant in the system to which the sample was added, when the elastase specific activity in the back skin of hairless mice not irradiated with ultraviolet rays was 1, was calculated. The results are shown in FIG.

Results of Elastase Production Inhibition Test As a result of examining the elastase production inhibitory action of each test sample, as shown in FIG. 7, in the negative control, the specific activity of elastase was increased by ultraviolet irradiation. The increase in the specific activity of the sample elastase consisting of squalic acid derivatives was suppressed. Therefore, it was found that the product of the present invention has an excellent elastase production inhibitory action. The test results suggested that the product of the present invention has an effect of preventing or improving skin aging caused by activation of MMP production.

Skin elasticity improvement test As one of the skin aging, there is a decrease in skin elasticity. In this test, the effect of preventing or improving the reduction of skin firmness of the product of the present invention was examined using the skin elasticity as an index. The skin elasticity indicates the elasticity of the skin, and the firmer skin has a higher elasticity value. A lotion prepared by removing squaric acid and organic acid from the composition described in Table 2 was used as a test sample, and the lotion described in Table 2 was used as a negative control. Each subject (subjects A, B, C, D, E, F, and G) ages 30-40 years old has a lotion containing squaric acid and organic acid listed in Table 2 on the left eyelid, and a negative subject on the right eyelid. An appropriate amount of each lotion was applied twice a day and continued for one month. And the elasticity of the buttocks of the right eye and the left eye of each subject after one month was measured. The elasticity was measured using a skin viscoelasticity measuring instrument (CUTOMETER SEM474 COURAGE + KHAZAKA Electronic GmbH) at the start of the test and after one month of the test. The measurement of elasticity using a skin viscoelasticity measuring instrument as measurement conditions was set to measurement in an environment always at 25 ° C. and humidity of 50%. The results of this test are shown in FIG.

Results of skin elasticity improvement test As a result of testing the skin elasticity improvement effect of the lotion containing the squaric acid derivative as the test sample and the lotion as the negative control, as shown in FIG. 8, all subjects compared with the negative control. Thus, by applying a lotion containing a squaric acid derivative, a remarkable improvement in skin elasticity was observed. Therefore, it was found that the product of the present invention has an effect of improving the skin elasticity and suppressing or improving the reduction of skin firmness.

Anti-inflammatory test with inhibitory effect on complement activity This test is an element that induces inflammation and induces inflammatory cells, and an element that induces degranulation from mast cells and causes type I allergic symptoms The inhibitory effect on complement production was used as an index of anti-inflammatory effect. Samples to be used in this test include squaric acid-2-α-tocopherol, squaric acid-2-calcium sulfate of Example 8 (hereinafter referred to as squaric acid-2-calcium sulfate), and 2-amino of Example 9. 10% DMSO aqueous solution of 1.0 mg / mL each of dipotassium glycyrrhizinate that has been confirmed to have anti-inflammatory action as a positive control, and as a negative control A 10% DMSO aqueous solution was used. The reagents used in this test were prepared by the method described below.
(A) Gelatin-Veronal Buffer Sodium Chloride 1.7 g, Barbital 0.115 g, Barbital Sodium 0.075 g, Calcium Chloride 0.015 g, Magnesium Chloride 0.010 g, Gelatin 0.2 g, Purified Water 100 mL are mixed and adjusted to pH 7.5, The total volume was adjusted to 200 mL with purified water.
(B) Sensitized sheep erythrocyte suspension
Shake the vial containing 8.5% sensitized sheep erythrocytes (Denka Seiken Co., Ltd.), add 2 volumes of gelatin-veronal buffer, mix, and centrifuge at 2000 rpm for 10 minutes to remove the supernatant. did. Gelatin-veronal buffer was then added again to resuspend the sensitized sheep erythrocytes. Use gelatin-veronal buffer to adjust the concentration of sensitized sheep erythrocytes so that when sensitized sheep erythrocytes are hemolyzed by adding 2.2 mL of 0.1% sodium carbonate to 200 mL of this resuspended solution, the absorbance at 540 nm is 0.455. Adjusted.
(C) 0.5 mL of purified water was added to complement solution dried serum powder (manufactured by DENKA SEIKEN for complement control 0.5 mL), and allowed to stand at low temperature for 20 minutes.
After adjusting the above (a) to (c), 2 mL of gelatin-veronal buffer and 200 μL of sample were added to the centrifuge tube and stirred. Next, 10 μL of complement solution was added thereto and stirred. Next, 200 μL of the sensitized sheep erythrocyte suspension was added and stirred, and then heated at 37 ° C. for 60 minutes. Next, after leaving still in ice water for 10 minutes, it centrifuged at 2000 rpm for 10 minutes, and the supernatant liquid was fractionated. The absorbance of the obtained supernatant at a wavelength of 540 nm was measured. In this test, for each sample, a system in which no complement solution was added in the course of the test was set as a blank. And the complement activity suppression rate of each sample was computed from the value of the light absorbency of each obtained sample and blank from the following formula 2. The results are shown in FIG.

Results of anti-inflammatory test using complement activity inhibitory action as an index. Results of test of complement activity inhibitory action of each test sample, as shown in FIG. Samples consisting of 7-9 squaric acid derivatives showed a high inhibition rate of complement activity. Therefore, it was found that the product of the present invention has superior complement activity inhibitory action and anti-inflammatory action based on complement activity inhibitory action as compared with conventional anti-inflammatory agents. From the test results, it was suggested that the product of the present invention has an effect of improving rough skin, preventing or improving atopy, and preventing or improving allergic dermatitis.

Anti-inflammatory test using hyaluronidase activity inhibitory action as an index This test is an index of anti-inflammatory action that inhibits the activity of hyaluronidase, an element that is activated during inflammation, destroys surrounding tissues, and easily invades cells that control inflammation. It was. Samples to be used in this test include squaric acid-2-α-tocopherol, squaric acid-2-calcium sulfate, 2-aminoethyl squaryl sulfate, and glycyrrhizic acid that has been confirmed to have anti-inflammatory activity as a positive control. A 10% DMSO aqueous solution of 1.0 mg / mL each of dipotassium and a 10% DMSO aqueous solution were used as a negative control. The reagents used in this test were prepared by the method described below.
(A) Hyaluronidase solution
8.0 mg of hyaluronidase (Type4.-S Sigma) was prepared by dissolving in 2 mL of 0.1 M acetic acid-sodium acetate buffer (pH 4.0).
(B) Enzyme activation solution
2.0 mg of Compound 48/80 (manufactured by Sigma) and 15.0 mg of calcium chloride dihydrate were prepared by dissolving in 4 mL of 0.1 M acetic acid-sodium acetate buffer (pH 4.0).
(C) Hyaluronic acid solution
8.0 mg of hyaluronic acid (manufactured by Sigma) was prepared by dissolving in 10 mL of 0.1 M acetic acid-sodium acetate buffer (pH 4.0).
(D) p-dimethylaminobenzaldehyde solution
5.0 g of p-dimethylaminobenzaldehyde was prepared by dissolving in 44 mL of glacial acetic acid and 6 mL of 10N hydrochloric acid.
(E) Potassium borate solution
2.24 g of potassium hydroxide was dissolved in 100 mL of 0.8 M boric acid aqueous solution to prepare.
After adjusting the above (a) to (e), 0.05 mL of the hyaluronidase solution was added to 0.1 mL of the sample, and allowed to stand at 37 ° C. for 20 minutes. Next, 0.1 mL of the enzyme activation solution was added and allowed to stand at 37 ° C. for 20 minutes. Next, 0.25 mL of hyaluronic acid solution was added and reacted at 37 ° C. for 40 minutes. Next, 0.1 mL of 0.4N sodium hydroxide aqueous solution was added to stop the reaction, and then 0.1 mL of potassium borate solution was added and heated in boiling water for 3 minutes. After cooling to room temperature, 3.0 mL of p-dimethylaminobenzaldehyde solution was added, and allowed to stand at 37 ° C. for 20 minutes, and then the absorbance at a wavelength of 585 nm was measured. In this test, for each sample, a system in which no hyaluronidase solution was added in the course of the test was set as a blank. Then, the hyaluronidase activity inhibition rate of each sample was calculated from the obtained absorbance value of each sample and the blank from the following Equation 3. The results are shown in FIG.

Results of anti-inflammatory test using hyaluronidase activity inhibitory action as an index As a result of testing the hyaluronidase activity inhibitory action of each test sample, as shown in FIG. The sample consisting of 9 squaric acid derivatives showed the same high inhibition rate of hyaluronidase activity. Therefore, it was found that the product of the present invention has a superior hyaluronidase activity inhibitory action comparable to conventional anti-inflammatory agents and an anti-inflammatory action based on the hyaluronidase activity inhibitory action. From the test results, it was suggested that the product of the present invention has an effect of improving rough skin, preventing or improving atopy, and preventing or improving allergic dermatitis.

Anti-inflammatory test using carrageenin footpad edema inhibitory action as an index This test was used as an index of carrageenin footpad edema inhibitory action in mice, which has been confirmed to have a significant correlation with anti-inflammatory action in humans. Samples to be tested in this test include squaric acid-2-α-tocopherol, squaric acid-2-calcium sulfate, 2-aminoethyl squaryl sulfate, and glycyrrhizic acid that has been confirmed to have anti-inflammatory activity as a positive control. Dipotassium 10.0 mg / mL each in 10% DMSO aqueous solution and 10% DMSO aqueous solution as a negative control were used. The thickness of the right hind footpad of female ICR mice (6 weeks old, 8 per group) was measured in advance with a dial thickness gauge. Next, 25 mL of the sample was carefully applied to the right hind limb with a finger. 1 hour after application, 25 μL of physiological saline containing 2.0% λ-carrageenan was subcutaneously injected subcutaneously into the right hind footpad. After subcutaneous injection, the thickness of the footpad was measured with a dial thickness gauge for a total of 4 hours every hour. did. The difference from the thickness of the footpad before subcutaneous injection of λ-carrageenan was calculated. And the carrageenin footpad edema suppression rate of each sample was computed from the following formula 4. The results are shown in FIG.
(Equation 4)
Carrageenan footpad edema inhibition rate (%) = (difference in footpad thickness in each sample or positive control / difference in footpad thickness in negative control) × 100

Results of anti-inflammatory test using carrageenin footpad edema inhibitory action as an index As a result of testing the carrageenin footpad edema inhibitory action of each test sample, as shown in FIG. Samples made of the squaric acid derivatives of Examples 7 to 9 showed a high carrageenan footpad edema inhibition rate. Therefore, it was found that the product of the present invention has superior carrageenin footpad edema inhibitory action and anti-inflammatory action based on carrageenin footpad edema inhibitory action as compared with conventional anti-inflammatory agents. From the test results, it was suggested that the product of the present invention has an effect of improving rough skin, preventing or improving atopy, and preventing or improving allergic dermatitis.

(Production Examples) Production of various cosmetic compositions Various cosmetic compositions according to the present invention were produced. Although the formulation example is shown below, this invention is not necessarily limited to these.

(Formulation Example 1) Milk Mass%
Squaric acid-2-magnesium phosphate 4.0
Squalane 5.0
Olive oil 5.0
Jojoba oil 5.0
Cetyl alcohol 1.5
Glycerol monostearate 2.0
Polyoxyethylene (20) cetyl ether 3.0
Polyoxyethylene (20) soorbitan monooleate 2.0
1,3-butylene glycol 1.0
Glycerin 2.0
P-Hydroxybenzoate ester
Residue with 100 purified water

(Formulation Example 2) Milk Mass%
Squaric acid-2-glucopyranoside 5.0
Sodium citrate 2.0
Hydrogenated soybean phospholipid 2.5
Glycerin 5.0
1,3-butylene glycol 5.0
Jojoba oil 5.0
Tri-2-ethylhexanoic acid 5.0
Glycerin 15.0
Carrageenan 0.1
Ethanol 5.0
Dipropylene glycol 5.0
Spherical silica 1.0
Perfume
Residue with 100 purified water

(Formulation example 3) Milk mass%
Dibenzyl squaric acid 5.0
1,3-butylene glycol 5.0
Glycerin 4.0
Polyethylene glycol 1600 0.5
Ethanol 5.0
Decamethylcyclopentasiloxane 5.0
Squalane 5.0
Olive oil 10.0
Jojoba oil 1.0
Diglyceryl dioleate 1.0
Sorbitan monostearate0.5
Cetyl alcohol 0.5
Stearyl alcohol 0.5
Nylon powder 0.5
Methyl paraoxybenzoate 0.1
Residue with 100 purified water

(Prescription Example 4) Lotion Mass%
Squalylaminopropyl phosphate 3.0
Sodium glutamate 1.0
1,3-butylene glycol 6.0
Glycerin 5.0
Polyethylene glycol 400 3.0
Olive oil 0.5
Polyoxyethylene (20) sorbitan monostearate 1.5
Polyoxyethylene (5) oleyl alcohol ether 0.3
Ethanol 10.0
Perfume Appropriate amount Dye Appropriate amount Phenoxyethanol 0.1
Citric acid 1.0
Sodium citrate 1.2
Residue with 100 purified water

(Formulation Example 5) Lotion Toner Mass%
Squaric acid-2-α-tocopherol 3.0
Potassium citrate 1.0
1,3-butylene glycol 6.0
Glycerin 4.0
Polyethylene glycol 2000 3.0
Olive oil 0.5
Sucrose monooleate 1.5
Polyoxyethylene (80) hydrogenated castor oil 0.3
Polyoxyethylene (20) sorbitan monococonut oil fatty acid ester 0.1
Ethanol 10.0
Perfume
Residue with 100 purified water

(Formulation Example 6) Lotion Mass%
Squaric acid-2-calcium phosphate 4.5
Glycerin 3.0
1,3-butylene glycol 5.0
Ethanol 15.0
Iron oxide 0.2
Zinc oxide 0.5
Kaolin 2.0
Trehalose 2.0
Dextrin 0.5
Photosensitive element 201 Appropriate amount Photosensitive element 401 Appropriate amount Fragrance Appropriate amount
Residue with 100 purified water

(Prescription Example 7) Lotion Mass%
Squaric acid-2-α-tocololienol 3.5
Sodium citrate 1.0
Dipropylene glycol 5.0
Raffinose 1.0
Ethanol 5.0
Phenoxyethanol 0.2
Pectin 0.01
Xanthan gum 0.05
Acetylglucosamine 0.05
Diisopropylamine dichloroacetic acid 0.2
γ-amino-β-hydroxybutyric acid 0.2
Sodium hyaluronate 0.001
Allantoin 0.2
N-menthyl glyceryl ether 0.2
Dipotassium glycyrrhizinate 0.2
Decarboxycarnosine hydrochloride 0.05
Perfume
Residue with 100 purified water

(Prescription Example 8) Cream mass%
Squaric acid-2-rhamnoside 5.0
Stearic acid 2.0
Glycerol monostearate2.0
Cetanol 3.0
Cholesterol 0.5
Vaseline 2.0
Squalane 10.0
Liquid paraffin 10.0
Dimethylpolysiloxane 1.0
Sodium glutamate 2.0
Glycerin 5.0
Dipropylene glycol 3.0
Nicotinamide 1.0
Methyl paraoxybenzoate 0.1
Butyl paraoxybenzoate 0.1
Perfume
Residue with 100 purified water

(Formulation example 9) Cream mass%
Squaric acid-2-magnesium sulfate 5.0
Calcium pyruvate 1.5
Dipropylene glycol 3.0
Sorbitol 2.0
Polyoxyalkylene modified silicone 1.0
Cross-linked methylphenyl polysiloxane 1.0
Octamethylcyclotetrasiloxane 5.0
Isotridecyl isononanoate 2.0
Isostearyl palmitate 2.0
Octyl methoxycinnamate 5.0
Methyl paraoxybenzoate 0.1
Polyoxyethylene sorbitan monostearate2.0
Trimethylsiloxysilicate 0.5
Ethanol 1.0
Perfume
Residue with 100 purified water

(Formulation Example 10) Face wash mass%
Butyl methyl squarate 4.5
Sodium aspartate 1.0
Methoxycinnamic acid 1.0
Myristic acid 25.0
Stearic acid 5.0
Tallow fatty acid 5.0
Propylene glycol 10.0
Potassium hydroxide 6.0
Palm oil fatty acid diethanolamide 6.0
Glycerol 1.0
1,3-butylene glycol 1.0
Dipotassium glycyrrhetinate 1.0
Preservative 0.1
Perfume
Residue with 100 purified water

(Prescription Example 11) Body soap mass%
Squaryldiaminobutane phosphate 4.5
Sodium citrate 2.0
N-acetylglutamic acid 1.0
Potassium laurate 15.0
Potassium myristate 5.0
Propylene glycol 5.0
Sorbitol 3.0
Polyethylene powder 0.5
Hydroxypropyl chitosan solution 0.5
Preservative appropriate amount
pH adjuster appropriate amount perfume appropriate amount
Residue with 100 purified water

(Prescription Example 12) Face wash mass%
Diisoproyl squarate 3.0
Glyoxylic acid 0.5
Glyceryl monopalmitate 3.0
Polyoxyethylene behenyl ether 2.0
Octyldodecyl laurate 5.0
Lauryl hydroxysulfobetaine 1.0
Polyoxyalkylene-modified organopolysiloxane 4.0
Glycerin 8.0
Trehalose 2.0
2-phenoxyethanol 0.5
Perfume
Residue with 100 purified water

(Formulation example 13) Powder foundation Mass%
Squaric acid-2-magnesium phosphate powder 4.0
Silicone-treated mica 25.0
Sericite 17.0
Hydrophobic treated silica 20.0
Titanium oxide 20.0
Spherical alumina powder 4.0
Dimethylpolysiloxane 4.0
Methylphenylpolysiloxane 1.0
Vaseline 3.0
Octyl methoxycinnamate 3.0
Sorbitan diisostearate 1.0
Antioxidant appropriate amount perfume appropriate amount paraoxybenzoic acid appropriate amount
Talc remaining

(Formulation Example 14) Soft gel foundation
Squaric acid diisopropyl phosphate 4.0
Sodium glycolate 1.0
Glyceryl monostearate0.5
Polyethylene glycol monostearate0.5
Cetanol 0.5
Squalane 1.0
Glyceryl trioctanoate 1.5
Dipentaerythritol fatty acid ester 0.2
Methyl polysiloxane 0.2
1,3-butylene glycol 10.0
Titanium oxide 5.0
Bengala 0.05
Yellow iron oxide 0.75
Black iron oxide 0.05
Talc 2.0
Sodium polyoxyethylene alkyl ether phosphate 0.1
Polyoxyethylene sorbitan monooleate 0.2
Sorbitan sesquioleate 0.2
Carboxyvinyl polymer 0.4
Calcium chloride 0.02
Perfume Appropriate amount Preservative Appropriate amount
Residue with 100 purified water

(Formulation Example 15) Emulsified liquid foundation Mass%
Squaryl 2-palmitate 3.2
Sodium glutamate 1.5
Octamethylcyclotetrasiloxane 20.0
Polyoxyethylene (6) oleyl ether 4.0
Polyoxyethylene hydrogenated castor oil 3.0
Aluminum monostearate 0.01
Liquid paraffin 12.0
Dimethylpolysiloxane 5.0
12-hydroxystearic acid 1.0
Nylon powder 4.5
Black iron oxide 1.5
Yellow iron oxide 3.0
Titanium oxide 5.0
Red iron oxide 2.0
Butyl paraoxybenzoate 0.2
Sorbitol 7.0
Residue with 100 purified water

(Prescription Example 16) Lipstick mass%
Ditetrahexyl squaric acid 2.5
Paraffin wax 5.0
Ceresin 5.0
Candelilla wax 2.0
Microcrystalline wax 1.0
Polyethylene wax 1.0
Ethylene propylene copolymer 1.0
Hydrogenated polyisobutene 10.0
Diisostearyl malate 15.0
Isotridecyl isononanoate 12.0
Neopentyl glycol dicaprate8.0
Octyldodecanol 3.0
Squalane 5.0
Phytosteryl oleate 3.0
Methylphenylpolysiloxane 3.0
DL-α-Tocopherol 0.1
Red No. 201 0.4
Red No. 202 0.2
Yellow No.4 0.5
Mica titanium 7.0
Glyceryl trioctanoate

(Prescription Example 17) Lipstick mass%
Squaric acid-2-α-tocopherol 3.0
Gallic acid 1.0
Titanium dioxide 4.5
Red No. 201 2.5
Ceresin 4.0
Candelilla wax 8.0
Carnauba wax 2.0
Castor oil 30.0
Isostearic acid diglyceride 40.0
Polyoxyethylene hydrogenated castor oil (20EO) 1.0
Methyl ethyl polysiloxane 5.0
Glycerin 2.0
Perfume Appropriate amount Antioxidant Appropriate amount
Residue with 100 purified water

(Formulation Example 18) Hair Shampoo Mass%
Dioctyldodecyl squarate 3.0
Potassium citrate 1.5
N-lauroylmethyl taurine sodium 7.0
Lauroyl sarcosine sodium 6.0
Lauryldimethylbetaine 2.5
Palm oil fatty acid diethanolamide 4.0
Propylene glycol 5.0
2-phenoxyethanol 1.0
Hydroxyethyl cellulose 0.5
Residue with 100 purified water

(Prescription Example 19) Hair Shampoo Mass%
Squaric acid-2-deoxymannosyl glucoside 3.0
Sodium citrate 1.5
Aspartic acid 1.0
Primary amine acrylic polymer 1.0
Sodium polyoxyethylene alkyl ether sulfate 18.0
Alkylamidopropylbetaine 3.0
Lauryldimethylamine oxide 1.0
Polyoxyethylene hydrogenated castor oil 5.0
Fatty acid diethanolamide 6.0
Glycerin fatty acid ester 2.0
Cetostearyl alcohol 1.0
Cationized cellulose 0.4
0.4M phosphate buffer 5.0
Ethanol 2.0
Sodium edetate 0.1
Sodium benzoate 0.8
Dye Appropriate amount of fragrance Appropriate amount Methyl parahydroxybenzoate 0.1
Residue with 100 purified water

(Prescription Example 20) Hair rinse Mass%
Squaric acid-1,2-dihydroxyhexyl 4.0
Sodium pyrrolidonecarboxylate 1.0
Polyoxyethylene / methylpolysiloxane copolymer 2.0
Stearyltrimethylammonium chloride 1.0
Cetostearyl alcohol 3.0
Polyoxyethylene hydrogenated castor oil 1.0
Cationized cellulose 1.0
Isostearyl myristate 1.0
Propylene glycol 5.0
Hydroxybenzophenone 0.1
Perfume
Residue with 100 purified water

(Prescription Example 21) Hair rinse Mass%
Diethyl squarate 5.0
Sodium citrate 2.5
Hexadecanol 2.0
Octyldodecanol 2.0
Jojoba oil 0.5
Glyceryl monostearate ester 1.0
Cetyl 2-ethylhexanoate 1.5
1,3-butylene glycol 7.0
Methyl paraoxybenzoate 0.1
Perfume
Residue with 100 purified water

(Prescription Example 22) Hair Treatment Mass%
Di-o-aminophenyl squaric acid 3.0
Behenic acid 5.0
Stearic acid 3.0
Cetyltrimethylammonium chloride 8.5
Diallyl chloride (12-18) dimethylammonium 0.5
Cationized keratin hydrolyzate 0.2
Ceramide 3 0.1
Amino-modified silicone emulsion 0.2
Dipentaerythritol fatty acid ester 0.3
Hydroxymethoxybenzophenone sulfonic acid 0.3
Diethylene glycol monoethyl ether 1.0
Benzyloxyethanol 0.5
Hydroxyethyl cellulose 0.4
Sodium citrate 2.0
Perfume
Residue with 100 purified water

(Prescription Example 23) Hair Treatment Mass%
Squalyl distearate 3.0
Sodium glycolate 1.5
Dimethylpolysiloxane 3.0
Amino-modified silicone 0.6
Polyoxyethylene methylpolysiloxane copolymer 0.5
Ethanol 10.0
Propylene glycol 6.0
Xanthan gum 0.2
Polyoxyethylene methyl polysiloxane copolymer 2.0
Sulfated cellulose 2.0
Antiseptic agent
Residue with 100 purified water

(Prescription Example 24) Hair set agent% by mass
Myristic acid-2-squaryl ester 2.5
Tartaric acid 1.0
Liquid paraffin 15.0
Polyoxypropylene diglyceryl ether 3.0
Polyoxyethylene polyoxypropylene glycol 2.0
Setanol 0.5
Sorbitan monostearate0.5
Polyoxyethylene sorbitan monostearate1.0
Glycerin 5.0
Methylpolysiloxane 2.0
Polyvinylpyrrolidone 1.0
Paraoxybenzoic acid 0.2
Perfume
Residue with 100 purified water

(Prescription Example 25) Hair set agent% by mass
Squaric acid-1,2-dipropyl ether 2.0
Sodium pyruvate 0.8
Liquid paraffin 8.0
Glyceryl tri-2-ethylhexanoate4.0
Polyoxyethylene cetyl ether 2.0
Glycerol monostearate2.0
Distearyldimethylammonium chloride 0.8
Stearyltrimethylammonium chloride 0.4
Myristyl myristate 2.0
Cetanol 2.0
Maltitol 2.0
Glycerin 10.0
Methyl paraoxybenzoate 0.2
Propyl paraoxybenzoate 0.2
Perfume
Residue with 100 purified water

(Prescription Example 26) Hair dye mass%
(First agent)
1-Butyl-2-hydroxypropyl squaric acid 2.0
Sodium citrate 0.8
Ammonia aqueous solution 5.0
Paraaminophenol 0.3
2,6-diaminopyridine 0.1
Hydroxyethyl cellulose 2.5
Oleyl alcohol 5.0
Propylene glycol 2.0
Pantothenyl ethyl ether 0.2
Astaxanthin laurate 0.3
Sodium sulfite 1.0
Edetate tetrasodium 0.2
Monoethanolamine Appropriate amount of purified water Remaining amount (second agent)
Hydrogen peroxide (35%) 15.0
Squaric acid-2-rutinoside 3.0
N-Vinylpyrrolidone-N, N-dimethylaminoethyl
Methacrylate copolymer 2.5
Propylene glycol 10.0
Stearyltrimethylammonium chloride 0.5
Lactic acid 0.2
Appropriate amount of dye
Residue with 100 purified water

(Prescription Example 27) Permanent wave agent mass%
(First agent)
Dibenzylsquaryl 3.5
Glycolic acid 0.5
Ammonium thioglycolate 6.0
Organopolysiloxane 2.0
Carnitine 0.3
Cysteine derivatives 0.4
28% ammonia water 1.5
Monoethanolamine 2.5
EDTA 0.2
POE oleyl ether 0.3
Purified water remaining amount (second agent)
Di- (dichlorophenyl) squaric acid 3.0
Sodium bromate 7.0
Liquid paraffin 0.2
POE nonylphenyl ether 0.5
Lauryldimethylaminoacetic acid betaine 2.0
Purified water remaining

(Formulation example 28) Hair nourishing and hair restorer
Squaric acid-2-α-tocopherol 5.0
Sodium glutamate 2.0
Ethanol 60.0
DL-α-tocopherol acetate 0.5
Pepper tincture 0.5
Aloe extract 3.0
Resorcin 0.5
Dipotassium glycyrrhizinate 0.5
Carboxymethylchitin 0.5
Decamethylcyclopentasiloxane 0.1
Arginine 0.25
Glutamine 0.25
Antibacterial agent appropriate amount perfume appropriate amount
Residue with 100 purified water

(Formulation Example 29) Bath agent mass%
Squaric acid-2-magnesium phosphate powder 5.0
Sodium bicarbonate 60.0
Borax 5.0
Sodium hyaluronate 1.0
Hydroxypropyl methylcellulose 1.0
Karin extract 5.0
Antibacterial agent appropriate amount perfume appropriate amount
Anhydrous sodium sulfate

(Formulation example 30) Beauty nail material mass%
Squaric acid-2-tetradecyl 2.5
Sodium citrate 1.0
Fluorine-modified polysiloxane 12.0
Versatic acid glycidyl ester modified alkyd resin 6.0
Silicone-based graft copolymer 2.0
Isopropyl alcohol 3.0
n-Butanol 1.0
Ethyl acetate 20.0
Toluene 10.0
N-Butyl acetate remaining

(Prescription Example 31) Beauty nail material mass%
Squaric acid-1,2-isopropyl 2.5
Calcium succinate 1.0
Isobutyl methacrylate copolymer 18.0
Acrylamide resin 8.0
Acetyltributyl citrate 1.5
Sucrose acetate isobutyrate 4.5
Ethyl acetate 6.0
Butyl acetate 14.5
Isopropyl alcohol 2.0
Toluene remaining

(Prescription Example 32) Coating preparation A formulation solution in which gauze or liniment cloth is mixed with squalylaminopropyl phosphate, squaric acid-2-α-tocopherol, and a moisturizer, anti-inflammatory agent, cell activator, antioxidant, etc. And attach to the wound. Further, an application method in which these are directly applied locally and covered with gauze or the like may be adopted.

It is a figure which shows the effect | action with respect to the melanin production amount of a squaric-acid derivative. It is a figure which shows the effect | action with respect to the melanocyte expression number of a squaric acid derivative. It is a figure which shows the NBT reduction | decrease rate of a squaric acid derivative. It is a figure which shows the lipid peroxidation suppression rate of a squaric acid derivative. It is a figure which shows the effect | action with respect to the collagen production rate of a squaric acid derivative. It is a figure which shows the effect | action with respect to collagenase production of a squaric acid derivative. It is a figure which shows the effect | action with respect to elastase production of a squaric acid derivative. It is a figure which shows the effect with respect to skin elasticity of the cosmetics composition containing a squaric acid derivative. It is a figure which shows the complement activity suppression rate of a squaric acid derivative. It is a figure which shows the hyaluronidase activity inhibition rate of a squaric acid derivative. It is a figure which shows the carrageenan footpad edema suppression rate of a squaric acid derivative.

Claims (2)

A cosmetic composition comprising at least one selected from a squaric acid derivative represented by the general formula 1 or a salt thereof (excluding squaric acid dibutyl ester).

: (General formula 1)

^-O-R 3 :( Formula 2)

^-S-R 3 :( Formula 3)

-PO ₃ -R ⁴ :( general formula 4)

-SO ₃ -R ⁴ :( Formula 5)

: (General formula 6)

: (General formula 7)

^-CO-R 5 :( Formula 8)

^-O-R 6 :( Formula 9)

[R ¹ and R ^{2 in} General Formula 1 are independently of each other a hydroxyl group, a halogen, a lower alkoxy group, a halogenated lower alkoxy group, a lower alkenyloxy group, a halogenated lower alkenyloxy group, a carboxyl group, or a lower alkoxycarbonyl. Group, substituted lower alkoxycarbonyl group, mercapto group, lower alkylthio group, aliphatic hydrocarbon group, substituted aliphatic hydrocarbon, aromatic hydrocarbon group or heterocyclic group (aromatic hydrocarbon group and The heterocyclic group is halogen, hydroxyl group, carboxyl group, amino group, lower alkyl group, lower alkenyl group, halogenated lower alkyl group, halogenated lower alkenyl group, lower alkoxy group, lower alkenyloxy group, halogenated lower alkoxy. Group, halogenated lower alkenyloxy group, merca An aliphatic hydrocarbon group, an aromatic hydrocarbon group or a heterocyclic group (which may have a substituent of 1 to 5 selected from the group consisting of Group hydrocarbon group and heterocyclic group are halogen, hydroxyl group, carboxyl group, amino group, lower alkyl group, lower alkenyl group, halogenated lower alkyl group, halogenated lower alkenyl group, lower alkoxy group, lower alkenyloxy group 1 to 5 substituents selected from the group consisting of a halogenated lower alkoxy group, a halogenated lower alkenyloxy group, a mercapto group and a lower alkylthio group), or a general formula 2 or a general formula 3 a group represented by (formula 2 and 3 in R ³ is optionally substituted aliphatic hydrocarbon group, an amino group, an alicyclic hydrocarbon group, Fang Family hydrocarbon group, heterocyclic group, sugar residues, phosphate groups or the general formula substituted phosphate group represented by 4 (R ⁴ in the formula 4 is an alkyl group or an aminoalkyl group of C1 -C6) A sulfate group or a substituted sulfate group represented by the general formula 5 (R ⁴ in the general formula 5 is a C1-C6 alkyl group or aminoalkyl group), a tocopherol adduct represented by the general formula 6, and a general formula 7 A tocotrienol adduct or a group represented by the general formula 8 (R ⁵ in the general formula 8 is an aliphatic hydrocarbon group or an aromatic hydrocarbon group which may be substituted, or a group represented by the general formula 9: (R ^{6 in} general formula 9 is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group))). However, R ¹ and R ² are not both hydroxyl groups. ] The cosmetic composition according to claim 1, wherein the cosmetic composition is a whitening cosmetic composition.

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