JP5979155B2 - Cosmetics containing cysteine derivatives and alcohol - Google Patents

Description

  The present invention relates to a cosmetic containing (A) a specific cysteine derivative or a salt thereof, and (B) a specific alcohol. Furthermore, the present invention relates to (C) a cosmetic containing a specific amino acid in addition to the above (A) and (B).

  Conventionally, whitening cosmetics containing various whitening agents have been proposed in order to prevent skin darkening, spots and freckles and to keep the original white skin. Patent Document 1 describes that a cysteine derivative obtained by esterifying L-2-methylthiazolidine-2,4-dicarboxylic acid or a salt thereof is useful as a whitening agent. Furthermore, Patent Document 2 describes that 2-methylthiazolidine-2,4-dicarboxylic acid or a derivative thereof has a whitening action. However, these derivatives have not been put into practical use because they are easily decomposed and are not sufficiently stable.

  In order to solve this problem, development of new cysteine derivatives having further improved stability is in progress. However, the derivative has a problem in solubility, and further improvement in the poor usability and transdermal absorbability due to the solubility has been demanded.

JP 2009-227660 A JP 2010-12239 A

  The subject of this invention is improving the solubility of a cysteine derivative and providing the cosmetics excellent in a usability | use_condition and transdermal absorbability.

  As a result of intensive research, it is possible to solve the problem of solubility by using a cysteine derivative and a specific alcohol, and optionally a specific amino acid in combination, and to provide a cosmetic with excellent usability and transdermal absorbability. The present inventors have found that this can be done and have completed the present invention.

［式中、
Ｘ及びＹは、それぞれ独立して、ＯＲ^１、ＮＨＲ^２（式中、Ｒ^１及びＲ^２は、それぞれ独立して、水素原子またはＣ_１−２２アルキル基を示す。）であり；
Ｚは、水素原子またはＣ_１−２２アルキル基を示し；
Ｗは、Ｃ_１−２２アルキル基、Ｃ_１−２２アルコキシ基またはＣ_１−２２アルキルアミノ基を示す。］
および
（Ｂ）アルコール
を含有する化粧料。
２． （Ａ）システイン誘導体またはその塩が、Ｎ−アセチル−２−メチルチアゾリジン−２，４−ジカルボン酸、Ｎ−アセチル−２−メチルチアゾリジン−２，４−ジカルボン酸−２−エチルエステル、およびそれらの塩から選択される１種以上である上記１記載の化粧料。
３． （Ｂ）アルコールが、Ｃ_１−６一価アルコール、多価アルコール、Ｃ_８−２２一価アルコール、および芳香族アルコールから選択される１種以上である上記１または２に記載の化粧料。
４． （Ｂ）アルコールが、エタノール、プロパノール、イソプロパノール、ブタノール、グリセリン、ジグリセリン、エチレングリコール、１，３−ブチレングリコール、プロピレングリコール、ジプロピレングリコール、イソプレングリコール、１，２−ペンタンジオール、１，３−ペンタンジオール、１，３−プロパンジオール、３−メチル−１，３−ブタンジオール、エチルヘキシルグリセリン、ポリエチレングリコール、セチルアルコール、ラウリルアルコール、イソステアリルアルコール、ステアリルアルコール、オレイルアルコール、ミリスチルアルコール、オクチルドデカノール、ベヘニルアルコール、ラノリンアルコール、セトステアリルアルコール、デシルテトラデカノール、ヘキシルデカノール、フェノキシエタノールおよびベンジルアルコールから選択される１種以上である上記１〜３のいずれか一項に記載の化粧料。
５． （Ｂ）アルコールがエタノール、イソプロパノール、１，３−ブチレングリコール、プロピレングリコール、ジプロピレングリコール、１，２−ペンタンジオール、エチルヘキシルグリセリン、ポリエチレングリコール、３−メチル−１，３−ブタンジオール、フェノキシエタノール、およびベンジルアルコールから選択される１種以上である上記１〜４のいずれか一項に記載の化粧料。
６． さらに（Ｃ）アミノ酸を含有する上記１〜５のいずれか一項に記載の化粧料。
７． （Ｃ）アミノ酸が、アルギニン、リジン、ヒスチジン、オルニチン、グルタミン酸、アスパラギン酸、ピロリドンカルボン酸、グルタミン、アスパラギン、グリシン、アラニン、バリン、ロイシン、イソロイシン、セリン、スレオニン、プロリン、ヒドロキシプロリン、トリプトファン、フェニルアラニン、チロシンおよびメチオニンから選択される１種以上である上記６に記載の化粧料。
７−２ （Ｃ）アミノ酸が、アルギニン、グリシン、ピロリドンカルボン酸、プロリン、アラニン、ヒスチジン、リジン、セリン、イソロイシン、ロイシン、バリン、フェニルアラニン、トリプトファン、メチオニン、スレオニンから選択される１種以上である上記６に記載の化粧料。
８． （Ｃ）アミノ酸が、アルギニン、リジン、ヒスチジンおよびオルニチンから選択される１種以上である上記６に記載の化粧料。
９． （Ａ）システイン誘導体またはその塩がＮ−アセチル−２−メチルチアゾリジン−２，４−ジカルボン酸−２−エチルエステルまたはその塩であり、（Ｂ）アルコールが１，３−ブチレングリコールであり、（Ｃ）アミノ酸がアルギニンである上記６に記載の化粧料。
１０． （Ａ）システイン誘導体またはその塩と（Ｂ）アルコールの配合比が、（Ａ）／（Ｂ）＝１／３００００〜２０／１（ｇ／ｇ）である上記１〜９のいずれか一項に記載の化粧料。
１１． （Ａ）システイン誘導体またはその塩と（Ｃ）アミノ酸の配合比が、（Ａ）／（Ｃ）＝１／３００００〜２０／１（ｇ／ｇ）である上記６〜１０のいずれか一項に記載の化粧料。
１２． （Ｂ）アルコールと（Ｃ）アミノ酸の配合比が、（Ｂ）／（Ｃ）＝１／４０〜３００００／１（ｇ／ｇ）である上記６〜１１のいずれか一項に記載の化粧料。
１３． 美白化粧料である上記１〜１２のいずれか一項に記載の化粧料。That is, the present invention is as follows.
1. (A) A cysteine derivative represented by the general formula (I) or a salt thereof:

[Where:
X and Y are each independently OR ¹ , NHR ² (wherein R ¹ and R ² each independently represents a hydrogen atom or a C _1-22 alkyl group);
Z represents a hydrogen atom or a C _1-22 alkyl group;
W represents a C _1-22 alkyl group, a C _1-22 alkoxy group or a C _1-22 alkylamino group. ]
And (B) a cosmetic containing alcohol.
2. (A) a cysteine derivative or a salt thereof is N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid, N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid-2-ethyl ester, and their 2. The cosmetic according to 1 above, which is at least one selected from salts.
3. (B) The cosmetic according to 1 or 2, wherein the alcohol is one or more selected from C _1-6 monohydric alcohol, polyhydric alcohol, C _8-22 monohydric alcohol, and aromatic alcohol.
4). (B) The alcohol is ethanol, propanol, isopropanol, butanol, glycerin, diglycerin, ethylene glycol, 1,3-butylene glycol, propylene glycol, dipropylene glycol, isoprene glycol, 1,2-pentanediol, 1,3- Pentanediol, 1,3-propanediol, 3-methyl-1,3-butanediol, ethylhexylglycerin, polyethylene glycol, cetyl alcohol, lauryl alcohol, isostearyl alcohol, stearyl alcohol, oleyl alcohol, myristyl alcohol, octyldodecanol, Behenyl alcohol, lanolin alcohol, cetostearyl alcohol, decyltetradecanol, hexyldecanol, phenoxyethanol and The cosmetic according to any one of the above 1 to 3 is at least one selected from benzyl alcohol.
5. (B) the alcohol is ethanol, isopropanol, 1,3-butylene glycol, propylene glycol, dipropylene glycol, 1,2-pentanediol, ethylhexylglycerin, polyethylene glycol, 3-methyl-1,3-butanediol, phenoxyethanol, and Cosmetics as described in any one of said 1-4 which are 1 or more types selected from benzyl alcohol.
6). Furthermore, (C) Cosmetics as described in any one of said 1-5 containing an amino acid.
7). (C) the amino acid is arginine, lysine, histidine, ornithine, glutamic acid, aspartic acid, pyrrolidonecarboxylic acid, glutamine, asparagine, glycine, alanine, valine, leucine, isoleucine, serine, threonine, proline, hydroxyproline, tryptophan, phenylalanine, 7. The cosmetic according to 6 above, which is one or more selected from tyrosine and methionine.
7-2 (C) The amino acid is one or more selected from arginine, glycine, pyrrolidone carboxylic acid, proline, alanine, histidine, lysine, serine, isoleucine, leucine, valine, phenylalanine, tryptophan, methionine, threonine 6. Cosmetics according to 6.
8). (C) The cosmetic according to 6 above, wherein the amino acid is at least one selected from arginine, lysine, histidine and ornithine.
9. (A) The cysteine derivative or a salt thereof is N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid-2-ethyl ester or a salt thereof, (B) the alcohol is 1,3-butylene glycol, C) The cosmetic according to 6 above, wherein the amino acid is arginine.
10. (A) The compounding ratio of a cysteine derivative or a salt thereof and (B) alcohol is (A) / (B) = 1 / 30000-20 / 1 (g / g) Cosmetics described.
11 (A) The compounding ratio of the cysteine derivative or a salt thereof and the (C) amino acid is (A) / (C) = 1 / 30000-20 / 1 (g / g) Cosmetics described.
12 (B) Cosmetics as described in any one of said 6-11 whose compounding ratio of alcohol and (C) amino acid is (B) / (C) = 1 / 40-30000 / 1 (g / g). .
13. The cosmetic according to any one of 1 to 12 above, which is a whitening cosmetic.

  According to the present invention, it is possible to provide a cosmetic material that has a good feeling of use and is excellent in transdermal absorbability.

  The present invention is a cosmetic containing (A) a specific cysteine derivative or a salt thereof and (B) a specific alcohol.

[(A) Cysteine derivative]
The cysteine derivative of the present invention is a cysteine derivative represented by the general formula (I) or a salt thereof.

［式中、
Ｘ及びＹは、それぞれ独立して、ＯＲ^１、ＮＨＲ^２（式中、Ｒ^１及びＲ^２は、それぞれ独立して、水素原子またはＣ_１−２２アルキル基を示す。）、であり；
Ｚは、水素原子またはＣ_１−２２アルキル基を示し；
Ｗは、Ｃ_１−２２アルキル基、Ｃ_１−２２アルコキシ基またはＣ_１−２２アルキルアミノ基を示す。］

[Where:
X and Y are each independently OR ¹ , NHR ² (wherein R ¹ and R ² each independently represents a hydrogen atom or a C _1-22 alkyl group);
Z represents a hydrogen atom or a C _1-22 alkyl group;
W represents a C _1-22 alkyl group, a C _1-22 alkoxy group or a C _1-22 alkylamino group. ]

The terms used in this specification are defined below.
The “C _1-22 alkyl group” means a linear or branched hydrocarbon group having 1 to 22 carbon atoms, such as a methyl group, an ethyl group, an isopropyl group, a propyl group, a butyl group, Isobutyl group, sec-butyl group, tert-butyl group, pentyl group, sec-pentyl group, tert-pentyl group, isopentyl group, hexyl group, heptyl group, octyl group, 2-ethylhexyl group, tert-octyl group, nonyl group , Isononyl group, decyl group, isodecyl group, undecyl group, dodecyl group, tridecyl group, isotridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, isohexadecyl group, heptadecyl group, octadecyl group, isooctadecyl group, behenyl group, etc. Can be mentioned.
_{Examples of the} “C _1-16 alkyl group” include methyl group, ethyl group, isopropyl group, propyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, sec-pentyl group, tert-pentyl group. Group, isopentyl group, hexyl group, heptyl group, octyl group, 2-ethylhexyl group, tert-octyl group, nonyl group, isononyl group, decyl group, isodecyl group, undecyl group, dodecyl group, tridecyl group, isotridecyl group, tetradecyl group , Pentadecyl group, hexadecyl group, isohexadecyl group and the like.
_{Examples of the} “C _1-6 alkyl group” include methyl group, ethyl group, isopropyl group, propyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, sec-pentyl group, tert-pentyl group. Group, isopentyl group, hexyl group and the like.

The “C _1-22 alkoxy group” means a hydroxyl group substituted with the above “C _1-22 alkyl group”. For example, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, tert-butoxy group, pentyloxy group, hexyloxy group, heptyloxy group, octyloxy group, nonyloxy group, decyloxy group, undecyloxy group, dodecyloxy group, tridecyloxy group, tetradecyloxy group, pentadecyloxy group Hexadecyloxy group, heptadecyloxy group, octadecyloxy group, nonadecyloxy group, eicosyloxy group, heneicosyloxy group, docosyloxy group and the like.
_{Examples of the} “C _1-6 alkoxy group” include methoxy group, ethoxy group, propoxy group, isopropyloxy group, butoxy group, isobutoxy group, tert-butoxy group, pentyloxy group, hexyloxy group and the like.

The “C _1-22 alkylamino group” means an amino group substituted with the above “C _1-22 alkyl group”, and examples thereof include a methylamino group, an ethylamino group, a propylamino group, an isopropylamino group, and butyl. Amino group, isobutylamino group, tert-butylamino group, pentylamino group, hexylamino group, heptylamino group, octylamino group, nonylamino group, decylamino group, undecylamino group, dodecylamino group, tridecylamino group, tetra Examples include decylamino group, pentadecylamino group, hexadecylamino group, heptadecylamino group, octadecylamino group, nonadecylamino group, eicosylamino group, heneicosylamino group, docosylamino group and the like.
_{Examples of the} “C _1-6 alkylamino group” include methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, isobutylamino group, tert-butylamino group, pentylamino group, and hexylamino group. Can be mentioned.

  “Halogen atom” includes chlorine atom, bromine atom, fluorine atom and iodine atom.

  Each substituent in the general formula (I) will be described below.

X and Y are each independently OR ¹ and NHR ² (wherein R ¹ and R ² each independently represents a hydrogen atom or a C _1-22 alkyl group).

The “C _1-22 alkyl group” represented by R ¹ or R ² is preferably a C _1-6 alkyl group, more preferably a methyl group, an ethyl group or an isopropyl group, still more preferably an ethyl group. is there.

X is preferably OR ¹ (wherein R ¹ is as defined above); more preferably OR ¹ ′ (wherein R ¹ ′ is a hydrogen atom or a C _1-6 alkyl group (preferably Represents a methyl group, an ethyl group, or an isopropyl group); and more preferably a hydroxyl group, a methoxy group, an ethoxy group, or an isopropoxy group, and even more preferably a hydroxyl group or a methoxy group.

Y is preferably OR ¹ (wherein R ¹ is as defined above), more preferably OR ¹ ′ (wherein R ¹ ′ is as defined above), More preferred is a hydroxyl group, a methoxy group, an ethoxy group or an isopropoxy group, and even more preferred is a hydroxyl group or a methoxy group.

Z represents a hydrogen atom or a C _1-22 alkyl group.
The “C _1-22 alkyl group” represented by Z is preferably a C _1-6 alkyl group, and more preferably a methyl group. Z is preferably a hydrogen atom or a C _1-6 alkyl group, more preferably a hydrogen atom or a methyl group.

W represents a C _1-22 alkyl group, a C _1-22 alkoxy group or a C _1-22 alkylamino group.
The “C _1-22 alkyl group” represented by W is preferably a C _1-16 alkyl group, more preferably a methyl group, a nonyl group, or a pentadecyl group, and still more preferably a methyl group.
The “C _1-22 alkoxy group” represented by W is preferably a C _1-6 alkoxy group, more preferably a tert-butoxy group.
The “C _1-22 alkylamino group” represented by W is preferably a C _1-6 alkylamino group.

W is preferably a C _1-22 alkyl group or a C _1-22 alkoxy group, more preferably a C _1-16 alkyl group or a C _1-6 alkoxy group, still more preferably a methyl group, a nonyl group, A pentadecyl group and a tert-butoxy group are preferable, and a methyl group and a tert-butoxy group are particularly preferable.

  Specific examples of the cysteine derivative represented by the general formula (I) include N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid and N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid. Acid 2-ethyl ester is preferable, and N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid-2-ethyl ester is more preferable.

Examples of the salt of the cysteine derivative of the present invention include a salt with an inorganic base and a salt with an organic base.
Examples of the salt with an inorganic base include sodium salt, potassium salt, calcium salt, magnesium salt, zinc salt, silver salt, ammonium salt and the like.
As a salt with an organic base, for example, methylamine, diethylamine, trimethylamine, triethylamine, ethanolamine, diethanolamine, triethanolamine, ethylenediamine, tris (hydroxymethyl) methylamine, dicyclohexylamine, N, N′-dibenzylethylenediamine, guanidine , Pyridine, picoline, choline, cinchonine, meglumine, amino acids (arginine, lysine, etc.) and the like.
According to a method known per se, each salt can be obtained by reacting the cysteine derivative of the present invention with an inorganic base or an organic base.

  As described above, the cysteine derivative of the present invention can take various salt forms, but the effect of the present invention is significant when the salt form is not taken.

  Since the cysteine derivative of the present invention has an inhibitory effect on black melanin production, it can be used as a whitening agent, or a preventive or therapeutic agent for stains. These uses utilize the property that the cysteine derivative of the present invention exhibits a stable dosage form, but is decomposed into cysteine relatively quickly by an enzyme such as acylase at the site of action after percutaneous absorption. Is.

  The lower limit when the cysteine derivative of the present invention or a salt thereof is blended in a cosmetic is not particularly limited as long as the effect is exhibited, but 0.0001% by weight is preferably the lower limit. From the viewpoint that an effective effect can be exhibited, 0.001% by weight is more preferable, 0.01% by weight is more preferable, 0.1% by weight is more preferable, 0.5% by weight is more preferable, and 1% by weight. Is more preferable, and 2% by weight is more preferable. When a salt of a cysteine derivative is used, the weight of the cysteine derivative portion (free body) is within the above range.

  The upper limit when the cysteine derivative of the present invention or a salt thereof is blended into a cosmetic is not particularly limited as long as the effect is exhibited, but is preferably 20% by weight. 18% by weight is more preferred, 16% by weight is still more preferred, 12% by weight is even more preferred, 10% by weight is particularly preferred, and 5% by weight is particularly preferred. When a salt of a cysteine derivative is used, the weight of the cysteine derivative portion (free body) is within the above range.

  The method for producing the cysteine derivative represented by the general formula (I) (hereinafter sometimes abbreviated as cysteine derivative (I)) is not particularly limited, and is produced by combining known methods. be able to. Specifically, it can be synthesized by the following method, but is not limited thereto.

  Compound (IV), which is a precursor of cysteine derivative (I), can be synthesized by the following step 1, and then cysteine derivative (I) can be synthesized by step 2. Compound (IV) may or may not be purified as necessary.

Step 1
Cysteine or a compound represented by general formula (II) obtained by esterification or amidation of cysteine in advance (hereinafter abbreviated as compound (II) and the same applies to compounds represented by other formulas). ) To form a ring by reacting with compound (III) to obtain compound (IV)

(In the formula, each symbol is as defined above.)
Compound (IV) can be obtained by reacting compound (II) with compound (III) in water or an alcohol such as methanol or ethanol for 5 to 24 hours. Of compound (II), cysteine ethyl ester can be obtained, for example, by reacting cysteine in ethyl alcohol in the presence of hydrochloric acid or thionyl chloride at room temperature for about 5 to 24 hours. Among the compounds (II), cysteine amide is a protected cysteine and an amine in the presence of a dehydrating condensing agent such as EDCI.HCl (1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride), methylene chloride, The compound obtained by reacting in a solvent such as N, N-dimethylformamide (DMF) at room temperature for 5 to 24 hours can be obtained by deprotection.

Step 2

(In the formula, A represents a halogen atom, and other symbols are as defined above.)
Cysteine derivative (I) can be synthesized by reacting compound (IV) with compound (V) or compound (V ′) in the presence or absence of a solvent and in the presence or absence of a base. Examples of the solvent include THF (tetrahydrofuran), ethyl acetate, isopropyl acetate, acetonitrile, acetone, ethanol, methanol, dichloromethane, water, or a mixture thereof, preferably THF, ethyl acetate, isopropyl acetate, acetonitrile, acetone, Dichloromethane, water, or a mixture thereof. Examples of the base include organic bases such as triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine, and inorganic bases such as lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium acetate, and potassium acetate. Preferably triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine, potassium carbonate, sodium carbonate.
The amount of compound (V) or compound (V ′) to be used is 1.0 to 5.0 mol, preferably 1.2 to 3.0 mol, per 1 mol of compound (IV). When using a base, the usage-amount of a base is 1.0-5.0 mol with respect to 1 mol of compound (IV), Preferably it is 1.2-4.0 mol. The reaction temperature is −10 to 100 ° C., preferably 0 to 90 ° C. The reaction time is 1 hour to 48 hours, preferably 3 hours to 20 hours.
Further, this may be converted to other cysteine derivatives (I) by esterification, amidation, hydrolysis or acid anhydride.

[(B) alcohol]
C _1-6 monohydric alcohol such as ethanol, propanol, isopropanol, butanol as the alcohol which is the component (B) present invention; glycerin, diglycerin, ethylene glycol, 1,3-butylene glycol, propylene glycol, dipropylene glycol Polyhydric alcohols such as isoprene glycol, 1,2-pentanediol, 1,3-pentanediol, 1,3-propanediol, 3-methyl-1,3-butanediol, ethylhexylglycerin, polyethylene glycol; cetyl alcohol; Lauryl alcohol, isostearyl alcohol, stearyl alcohol, oleyl alcohol, myristyl alcohol, octyldodecanol, behenyl alcohol, lanolin alcohol, cetostearyl alcohol, de C _8-22 monohydric alcohols such as siltetradecanol and hexyldecanol; aromatic alcohols such as phenoxyethanol and benzyl alcohol. Preferably, it is at least one selected from C _1-6 monohydric alcohol, polyhydric alcohol, and aromatic alcohol, more preferably ethanol, propanol, isopropanol, butanol, glycerin, diglycerin, ethylene glycol, 1 , 3-butylene glycol, propylene glycol, dipropylene glycol, isoprene glycol, 1,2-pentanediol, 1,3-pentanediol, 1,3-propanediol, 3-methyl-1,3-butanediol, ethylhexylglycerin , Polyethylene glycol, phenoxyethanol and benzyl alcohol, more preferably ethanol, isopropanol, 1,3-butylene glycol, propylene glycol, dipropylene glycol. One or more selected from coal, 1,2-pentanediol, ethylhexylglycerin, polyethylene glycol, 3-methyl-1,3-butanediol, phenoxyethanol, and benzyl alcohol, particularly preferably 1,3-butylene glycol and propylene One or more selected from glycols.

  The lower limit when the component (B) is blended into the cosmetic is not particularly limited as long as the effect is exhibited, but 0.0001% by weight is preferably the lower limit. From the viewpoint that an effective effect can be exhibited, 0.001% by weight is more preferable, 0.01% by weight is further preferable, 0.1% by weight is still more preferable, 0.5% by weight is even more preferable, and 1% by weight. % Is particularly preferred.

  The upper limit when the component (B) is blended into the cosmetic is not particularly limited as long as the effect is exhibited, but it is preferable to set the upper limit to 20% by weight. 18% by weight is more preferred, 16% by weight is still more preferred, 14% by weight is even more preferred, 12% by weight is even more preferred, and 10% by weight is particularly preferred.

The blending ratio of (A) cysteine derivative or salt thereof and (B) alcohol is not particularly limited as long as the effect is exhibited, but (A) / (B) = 1/30000 to 20/1 (g / g), preferably 1/10000 to 5/1 (g / g), more preferably 1/10000 to 1/1 (g / g), and even more preferably 1/1000 to 1. / 10 (g / g). When a salt of a cysteine derivative is used, the above ratio is calculated based on the weight of the cysteine derivative portion (free body).

[(C) amino acid]
The cosmetic of the present invention preferably further contains an amino acid that is component (C). As the component (C), arginine, lysine, histidine, ornithine, glutamic acid, aspartic acid, pyrrolidonecarboxylic acid, glutamine, asparagine, glycine, alanine, valine, leucine, isoleucine, serine, threonine, proline, hydroxyproline, tryptophan, phenylalanine , Tyrosine and methionine. Preferably, arginine, lysine, histidine, ornithine, glutamine, asparagine, glycine, alanine, valine, leucine, isoleucine, serine, threonine, proline, hydroxyproline, tryptophan, phenylalanine, tyrosine, methionine, more preferably arginine, Lysine, histidine, ornithine. Although it may be an optically active substance (L form or D form) or a racemic form (DL form), the L form is preferred. These may use 1 type and may mix and use 2 or more types.

  The acidic amino acid may be used as a free acidic amino acid or as a salt. The salt is not particularly limited as long as it is a salt that can be usually used in cosmetics, but metal salts such as sodium salt, potassium salt, calcium salt, magnesium salt, zinc salt, silver salt; ammonium salt, ethanolamine salt, etc. Amine salts; basic amino acid salts such as lysine and arginine; and alkali metal salts are preferred.

  The basic amino acid may be used as a free basic amino acid or as a salt. The salt is not particularly limited as long as it is a salt that can be usually used in cosmetics. However, inorganic acid salts such as hydrochloride and sulfate; organic acid salts such as acetate and citrate; glutamic acid and aspartic acid and the like Examples thereof include acidic amino acid salts, and hydrochloride is preferable.

  The lower limit when the component (C) is blended into the cosmetic is not particularly limited as long as the effect is exhibited, but 0.0001% by weight is preferably the lower limit. From the viewpoint that an effective effect can be exhibited, 0.001% by weight is more preferable, 0.01% by weight is further preferable, 0.1% by weight is still more preferable, 0.5% by weight is even more preferable, and 1% by weight. % Is particularly preferred.

  The upper limit when the component (C) is blended into the cosmetic is not particularly limited as long as the effect is exhibited, but 20% by weight is preferably set as the upper limit. 18% by weight is more preferred, 16% by weight is still more preferred, 14% by weight is even more preferred, 12% by weight is even more preferred, and 10% by weight is particularly preferred.

  The compounding ratio of (A) cysteine derivative or salt thereof and (C) amino acid is not particularly limited as long as the effect is exhibited, but (A) / (C) = 1/30000 to 20/1 (g / g), preferably 1/10000 to 5/1 (g / g), more preferably 1/10000 to 1/1 (g / g), and even more preferably 1/1000 to 1. / 10 (g / g). When a salt of a cysteine derivative is used, the above ratio is calculated based on the weight of the cysteine derivative portion (free body).

  The blending ratio of (B) alcohol and (C) amino acid is not particularly limited as long as the effect is exhibited, but is (B) / (C) = 1/40 to 30000/1 (g / g). , Preferably 1/20 to 10000/1 (g / g), more preferably 1/10 to 1000/1 (g / g), and even more preferably 1/1 to 10/1 (g). / G).

  In addition to the above (A) and (B) and (C), the cosmetic of the present invention usually contains various components that can be used in cosmetics (including pharmaceutical external preparations and quasi drugs). You may mix | blend in the range which does not inhibit the effect of invention. For example, oily components, surfactants, amino acid derivatives, water-soluble polymers, bactericides and antibacterial agents, anti-inflammatory agents, analgesics, antifungal agents, keratin softening release agents, skin coloring agents, hormone agents, UV absorbers , Hair restorer, whitening agent, antiperspirant and astringent active ingredient, sweat deodorant, vitamin agent, vasodilator, crude drug, pH adjuster, viscosity adjuster, pearlizing agent, natural fragrance, synthetic fragrance, pigment, oxidation Examples include inhibitors, preservatives, emulsifiers, fats and waxes, silicone compounds, perfume oils and the like.

  The cosmetic of the present invention can be obtained by appropriately mixing and stirring the constituent components. It can also be suitably heated to 40 ° C to 90 ° C.

  In the present invention, cosmetics are a concept including quasi-drugs. There is no restriction | limiting in particular in the form, It can take arbitrary forms, such as liquid form, paste form, gel form, solid form, and powder form. Specifically, lotion, lotion, cream, milk, serum, shampoo, hair rinse, hair conditioner, hair mousse, hair gel, hair wax, enamel, foundation, eyeliner, eyebrow pencil, mascara, eye shadow, teak, lipstick , Funny, powder, pack, pack mask, perfume, cologne, facial cleansing foam, cleansing foam, cleansing oil, cleansing gel, cleansing milk, toothpaste, soap, aerosol, bath preparation, hair nourishing agent, sunscreen.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

[Synthesis of Component A]
[Synthesis Example 1] N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid-2-ethyl ester (may be abbreviated as N-Ac-CP2Et in this specification)

L-cysteine hydrochloride monohydrate (100 g, 569 mmol) was dissolved in water (200 ml), and then a 6N aqueous sodium hydroxide solution was added to adjust the pH to 5.03. The reaction mixture was heated to 40 ° C., pyruvic acid ethyl ester (76 ml, 684 mmol) was added slowly, stirred at 40 ° C. for 3.5 hours, and 2-methylthiazolidine-2,4-dicarboxylic acid-2-ethyl ester. An ester was obtained (when the area ratio of the product in the reaction solution on the HPLC chart was confirmed, the ratio of trans isomer: cis isomer was about 55:45). After completion of the reaction, the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. Triethylamine (159 ml, 1141 mmol) was added to the obtained ethyl acetate solution under argon, acetyl chloride (61 ml, 858 mmol) was slowly added dropwise, and the reaction mixture was heated to reflux for 4 hours, and N-acetyl-2-methylthiazolidine was added. -2,4-Dicarboxylic acid-2-ethyl ester was obtained (when the area ratio of the product in the reaction solution on the HPLC chart was confirmed, the ratio of trans isomer: cis isomer was about 95: 5). After completion of the reaction, water (300 ml) was added and the pH was adjusted to 1.0 with HCl. After separating the aqueous layer, the organic layer was washed with water (300 ml), washed with saturated brine, and dried over anhydrous magnesium sulfate. About 500 g of the obtained ethyl acetate solution was concentrated, recrystallized by adding heptane, washed with heptane / ethyl acetate = 2/1, dried at 50 ° C. under reduced pressure, and N-acetyl-2-methylthiazolidine- Crystals of the trans form of 2,4-dicarboxylic acid-2-ethyl ester (the area ratio in the HPLC chart was confirmed, the ratio of the trans form was about 99%) were obtained (81 g, yield 55%). .
¹ H-NMR (CDCl ₃ ): δ; 1.27 (3H, t, J = 7.12 Hz), 1.94 (3H, s), 2.18 (3H, s), 3.40 (1H, d, J = 11.6 Hz), 3.56 (1H, dd, J = 5.5, 11.0 Hz), 4.20 (2H, t, J = 7.08 Hz), 5.00 (1H, d , J = 5.9 Hz), 9.10 (1H, brs).

[Synthesis Example 2]
N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid (N-acetyl-cysteinylpyruvic acid; hereinafter sometimes abbreviated as N-Ac-CP)

N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid-2-ethyl ester obtained by the same operation as in Synthesis Example 1 was dissolved in a mixed solvent of methanol (120 ml) and water (120 ml), and 2N NaOH. (182.4 ml) was added. The reaction was heated with stirring at 100 ° C. for 4 hours and at 80 ° C. overnight under an argon atmosphere. After allowing the reaction solution to cool to room temperature, AMBERLITEIR 120B H AG (about 250 g) was added to adjust the pH of the solution to 1-2. AMBERLITE was removed by filtration, the filtrate was concentrated under reduced pressure, ethyl acetate (200 ml) was added, and after stirring for 1 hour, white crystals were collected by filtration to give N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid. Obtained (15.99 g, 75%).
¹ H-NMR (DMSO-d ₆ ): δ; 1.73 (3H, s), 2.01 (3H, s), 3.36 (2H, d, J = 3.6 Hz), 5.26 ( 1H, t, J = 3.6 Hz).
MS spectrum m / z; [M + H] ⁺ = 234.0, [M−H] ⁻ = 232.0.

[Solubility Evaluation 1]

  1 g or 0.5 g of various alcohols shown in Table 1 were added to 0.1 g of the cysteine derivative crystals of Synthesis Example 1 or Synthesis Example 2 and stirred at 24 ° C. When the remaining crystal could be visually confirmed, 1 g of alcohol was further added and stirred at 24 ° C. This operation was repeated, and the concentration Y (wt%) at which the crystals were dissolved was determined. The solubility was evaluated according to the following criteria using this concentration Y.

A: Y ≧ 9.1
○: 9.1> Y ≧ 2.4
Δ: 2.4> Y ≧ 2.0
X: 2.0> Y

  From Table 1, when (B) specific alcohol was used together with (A) specific cysteine derivative of this invention, it turned out that the solubility to water improves remarkably. Thereby, the bad feeling of use resulting from solubility is also significantly improved.

(B) As specific alcohol, the effect was confirmed in _C1-6 monohydric alcohol, polyhydric alcohol, and aromatic alcohol.

  In particular, selected from ethanol, propylene glycol, dipropylene glycol, polyethylene glycol, phenoxyethanol, 3-methyl-1,3-butanediol, benzyl alcohol, 1,2-pentanediol, 1,3-butylene glycol, and ethylhexyl glycerin. It was found that more cysteine derivatives can be added to the cosmetic when one or more of the above are used.

[Solubility Evaluation 2]
In the proportions indicated in Table 2-5, Examples, and the compositions of Comparative Examples were prepared and the concentration of the composition at that time and C _1. The solution state was confirmed at the time of preparation, and the composition in which precipitation occurred was not evaluated. The solubility was evaluated according to the following criteria in comparison with the saturated concentration in water (C ₀ ).

_{◎: C 1 / C 0>} 2.0
_{○: 2.0 ≧ C 1 / C} 0> 1.5
Δ: 1.5 ≧ C ₁ / C ₀ > 1.0
×: 1.0 ≧ C ₁ / C ₀

[Percutaneous absorption evaluation]
Compositions of Examples and Comparative Examples were prepared at the ratios shown in Tables 2 to 5, and added at the top of a cup of a three-dimensional skin model placed in a 12-well plate at 200 μl / cup, and at the bottom at 1 ml / well of PBS ( phosphate-buffered saline) was added, and the mixture was allowed to stand at 37 ° C. for 5 hours. After standing, the lower solution was collected, and the cysteine derivative concentration (T ₁ ) was measured using HPLC. The transdermal absorbability was evaluated according to the following criteria in comparison with the obtained cysteine derivative concentration (T ₀ ) by adding an aqueous solution (Comparative Example 3 or 5) to the upper part of the skin model cup and conducting the same experiment.
In addition, the EPI-200X three-dimensional skin model made by Kurabo Industries was used for this percutaneous absorbability evaluation. As HPLC analysis conditions, in Examples 16 to 20, the column: Waters XTerra MS C18 5 μm 4.6 × 50 mm Column, eluent: 1% formic acid, 20% methanol, flow rate: 1.0 ml / min, The analysis was performed at a column temperature of 40 ° C., an injection amount: 20 μl, and a measurement wavelength of 210 nm. In Examples 21 to 29, the column: YMC-PackODS-A 150 YMC-Pack ODS-A 150 * 6.0 mmI. D. S-5 μm 12 nm (AA12S05-1506WT), eluent 50 mM NaH 2 PO 4 (pH = 2): MeOH = 60: 40, flow rate: 1.0 ml / min, column temperature: 40 ° C., injection volume: 10 μl, measurement wavelength 210 nm analyzed.

_{◎: T 1 / T 0>} 2.0
○: 2.0 ≧ T ₁ / T ₀ > 1.5
Δ: 1.5 ≧ T ₁ / T ₀ > 1.0
×: 1.0 ≧ T ₁ / T ₀

  From Table 2, it was found that the solubility was further improved when the component (C) was further added to the composition containing the components (A) and (B) (Examples 16 and 17 and 18) (Comparison between Example 19 and Example 20).

  From Table 3, the cosmetics containing the (A) component, the (B) component, and the (C) component have good solubility (thus, the poor feeling of use due to the solubility is remarkably improved). It can also be seen that a composition having good transdermal absorbability can be obtained.

Similar results were obtained when the cysteine derivative of Synthesis Example 2 was used instead of the cysteine derivative of Synthesis Example 1.

  From Table 5, it was found that when component (B) was added to component (A), transdermal absorbability was improved, and when component (C) was further added, it was further improved. In addition, it turns out that the improvement of transdermal absorbability tends to become more remarkable than the improvement of solubility.

  The cosmetics of this invention are illustrated below. Both are cosmetics with excellent usability and transdermal absorbability.

* 1: Any of the mixtures 1 to 5 in Table 14 can be used * 2: Any of the extracts 1 to 59 in Table 15 can be used

  In the above formulation examples, BG is 1,3 butylene glycol, PG is propylene glycol, DPG is dipropylene glycol, PEG is polyethylene glycol, PPG is polypropylene glycol, PVP is polyvinylpyrrolidone, and VA is vinyl acetate. Represents.

  The cosmetic of the present invention has been found to be excellent in use feeling and transdermal absorbability. As a result, it has become possible to provide cosmetics that are more effective than conventional whitening cosmetics.

Claims (13)

(A) A cysteine derivative represented by the general formula (I) or a salt thereof:

[Where:
X and Y are each independently OR ¹ , NHR ² (wherein R ¹ and R ² each independently represents a hydrogen atom or a C _1-22 alkyl group);
Z represents a hydrogen atom or a C _1-22 alkyl group;
W represents a C _1-22 alkyl group, a C _1-22 alkoxy group or a C _1-22 alkylamino group. ]
And (B) a cosmetic containing alcohol.   (A) a cysteine derivative or a salt thereof is N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid, N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid-2-ethyl ester, and their The cosmetic according to claim 1, wherein the cosmetic is at least one selected from salts. The cosmetic according to claim 1 or 2, wherein the alcohol (B) is at least one selected from C _1-6 monohydric alcohol, polyhydric alcohol, C _8-22 monohydric alcohol, and aromatic alcohol.   (B) The alcohol is ethanol, propanol, isopropanol, butanol, glycerin, diglycerin, ethylene glycol, 1,3-butylene glycol, propylene glycol, dipropylene glycol, isoprene glycol, 1,2-pentanediol, 1,3- Pentanediol, 1,3-propanediol, 3-methyl-1,3-butanediol, ethylhexylglycerin, polyethylene glycol, cetyl alcohol, lauryl alcohol, isostearyl alcohol, stearyl alcohol, oleyl alcohol, myristyl alcohol, octyldodecanol, Behenyl alcohol, lanolin alcohol, cetostearyl alcohol, decyltetradecanol, hexyldecanol, phenoxyethanol and The cosmetic according to any one of claims 1 to 3 is at least one selected from benzyl alcohol.   (B) the alcohol is ethanol, isopropanol, 1,3-butylene glycol, propylene glycol, dipropylene glycol, 1,2-pentanediol, ethylhexylglycerin, polyethylene glycol, 3-methyl-1,3-butanediol, phenoxyethanol, and The cosmetic according to any one of claims 1 to 4, wherein the cosmetic is one or more selected from benzyl alcohol.   The cosmetic according to any one of claims 1 to 5, further comprising (C) an amino acid.   (C) the amino acid is arginine, lysine, histidine, ornithine, glutamic acid, aspartic acid, pyrrolidone carboxylic acid, glutamine, asparagine, glycine, alanine, valine, leucine, isoleucine, serine, threonine, proline, hydroxyproline, tryptophan, phenylalanine, The cosmetic according to claim 6, wherein the cosmetic is at least one selected from tyrosine and methionine.   (C) The cosmetic according to claim 6, wherein the amino acid is at least one selected from arginine, lysine, histidine and ornithine.   (A) The cysteine derivative or a salt thereof is N-acetyl-2-methylthiazolidine-2,4-dicarboxylic acid-2-ethyl ester or a salt thereof, (B) the alcohol is 1,3-butylene glycol, C) The cosmetic according to claim 6, wherein the amino acid is arginine.   The blending ratio of (A) cysteine derivative or a salt thereof and (B) alcohol is (A) / (B) = 1 / 30000-20 / 1 (g / g). Cosmetics described in 1.   The compounding ratio of (A) cysteine derivative or a salt thereof and (C) amino acid is (A) / (C) = 1 / 30000-20 / 1 (g / g). Cosmetics described in 1.   The makeup ratio according to any one of claims 6 to 11, wherein the blending ratio of (B) alcohol and (C) amino acid is (B) / (C) = 1/40 to 30000/1 (g / g). Fee.   It is a whitening cosmetic, The cosmetic as described in any one of Claims 1-12.