JP5960505B2 - Composition for external use - Google Patents

Description

  The present invention relates to an external composition used as a cosmetic or quasi drug.

Pyrroloquinoline quinone (hereinafter sometimes abbreviated as “PQQ”) is widely present in the living world such as plants, animals, and microorganisms, and functions as a redox coenzyme essential for energy acquisition.
PQQ is known to have many physiological activities and is expected to be used as an active ingredient in pharmaceuticals, quasi drugs, cosmetics, or supplements. As such physiological activities, active oxygen and radical removal action, cell growth promotion action, ultraviolet absorption action, nerve growth factor production promotion action, brain function improvement action, hair growth action, facial color improvement action, melanin production suppression and whitening action, Mitochondrial activation and anti-fatigue effects are known.
Attempts have also been made to improve the stability of PQQ in formulations. For example, in Patent Document 1, oxazopyrroloquinoline, a salt thereof, or an ester thereof, which is a compound similar to PQQ, has physiological activities such as an active oxygen scavenging action, a melanin synthesis inhibitory action, and a lipid peroxide production inhibitory action. At the same time, it teaches excellent stability in the preparation.

  It is also known that components derived from legumes have various physiological activities. For example, Patent Document 2 discloses that an extract of a plant belonging to the genus Psophocarpus has a collagen production promoting action and a hyaluronic acid production promoting action. Patent Document 3 discloses that a soybean powder hydrolyzate has an effect of improving skin elasticity.

JP 2002-138011 A JP 2010-24222 JP 2004-75572 A

  An object of the present invention is to provide a useful external composition containing PQQ or a pharmaceutically acceptable salt thereof (hereinafter sometimes abbreviated as “salt”).

  The present inventor has repeatedly studied to solve the above problems, and a composition using a peptide and PQQ or a salt thereof in combination, when applied to the skin, reduces (i) the opening (area) of the pores. Make the pores less noticeable by reducing the depth and area of the surrounding depression (constriction of the pores), (ii) improve rough skin, (iii) reduce wrinkles and wrinkles, (iv) The present inventors have found that the skin texture is well-organized to improve the barrier function, (v) improve the moisture content of the skin, and (vi) improve the skin smear to give it a gloss.

This invention is completed based on the said knowledge, and provides the following external compositions.
Item 1. An external composition comprising pyrroloquinoline quinone or a pharmaceutically acceptable salt thereof and a peptide as active ingredients.
Item 2. Item 2. The composition for external use according to Item 1, wherein the peptide is a legume protein hydrolyzate.
Item 3. Item 3. The composition for external use according to Item 2, wherein the legume plant protein hydrolyzate is a soybean genus plant protein hydrolysate.
Item 4. Item 4. The composition for external use according to Item 3, wherein the soybean genus plant protein hydrolyzate is a hydrolyzate of soybean genus plant protein by protease.
Item 5. Item 5. The composition for external use according to Item 4, wherein the protease is thermolysin.
Item 6. Furthermore, the external composition in any one of claim | item 1 -5 containing a water-soluble polymer thickener.
Item 7. Item 7. The external composition according to any one of Items 1 to 6, comprising 0.00001 to 1% by weight of pyrroloquinoline quinone or a pharmaceutically acceptable salt thereof based on the total amount of the composition.
Item 8. The composition for external use in any one of claim | item 1 -7 containing 0.0001-5 weight% of peptides with respect to the whole quantity of a composition.
Item 9. The external composition in any one of claim | item 1 -8 containing 0.001-1000 weight part of peptides with respect to 1 weight part of pyrroloquinoline quinone or its pharmaceutically acceptable salt.
Item 10. The composition for external use according to any one of Items 1 to 9, wherein the peptide has a molecular weight of 300 to 10,000.
Item 11. Item 11. The external composition according to any one of Items 1 to 10, which is a mixed composition at the time of use, comprising a composition comprising pyrroloquinoline quinone or a pharmaceutically acceptable salt thereof and a composition comprising a peptide. .
Item 12. The external composition in any one of claim | item 6-11 which contains 0.001-5 weight% of water-soluble polymer thickeners with respect to the whole quantity of a composition.
Item 13. Water-soluble polymer thickener is cellulose thickener, thickening polysaccharide; dextran, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, alkyl methacrylate methacrylate copolymer, dextrin fatty acid ester, pectin Any one of Items 6 to 12, which is at least one selected from the group consisting of: (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer, dimethyldistearylammonium hectorite, and (acryloyldimethyltauronium ammonium / vinylpyrrolidone) copolymer The composition for external use described in 1.
Item 14. Item 14. A pore shrinkage agent comprising the composition for external use according to any one of Items 1 to 13.
Item 15. Item 14. A rough skin improving agent comprising the composition for external use according to any one of Items 1 to 13.
Item 16. Item 14. A skin texture improving agent comprising the composition for external use according to any one of Items 1 to 13.

The composition for external use of the present invention containing PQQ or a salt thereof and a peptide makes pores inconspicuous by reducing the opening (area) of the pores and reducing the depth and area of the surrounding depressions. That is, the composition for external use of the present invention has pore shrinkage action. As a result, the number of visible pores can be reduced and, as a result, the skin aesthetics are significantly improved.
Moreover, the composition for external use of this invention can improve rough skin. More specifically, rough skin occurs when the stratum corneum layer of the epidermis is thickened. However, the composition for external use of the present invention reduces keratin exfoliation by suppressing the thickening of the epidermis. A decrease in exfoliation indicates that rough skin is improved.
Moreover, the composition for external use of this invention improves a wrinkle.
Moreover, the composition for external use of this invention can prepare the skin texture (a state in which keratinocytes are lined up and there are intercellular lipids and natural moisturizing substances between cells) and improve the barrier function. In sensitive skin, the amount of intercellular lipid between the stratum corneum is less than that of healthy skin, and the skin texture is disturbed, the barrier function is lowered, the stimulation threshold is lowered, and the skin is easy to feel irritation It has become. Therefore, the composition for external use of this invention can be used conveniently for the skin quality improvement of sensitive skin.
Moreover, the composition for external use of this invention increases the moisture content of skin, ie, has a moisturizing effect.
Moreover, the composition for external use of the present invention improves skin darkening and gives gloss.
These effects become more remarkable by including a thickener.

The change of the evaluation value of the improvement score (a magnitude | size and a dent) of a pore by use of the composition of Example 1 for 4 weeks is shown. Fig. 3 shows the change in the number of pores by using the composition of Example 1 for 4 weeks. The change of the evaluation value of a wrinkle by the 4-week use of the composition of Example 1 is shown. The change of the evaluation value of a texture by using the composition of Example 1 for 4 weeks is shown. The evaluation value of the change of the amount of keratin moisture by use of the composition of Example 1 for 4 weeks is shown. The measurement image of the number of the pores before using the formulation of Example 1 and 8 weeks after use is shown. The measurement image of the texture (number of irregularities of pores) before using the preparation of Example 1 and after 8 weeks of use is shown. The change rate of the number of pores by use of the formulation of Example 1 and Comparative Examples 1 to 3 is shown. The change rate of a pore area by use of the formulation of Example 1 and Comparative Examples 1-3 is shown. The change of the score value used as the parameter | index of the improvement effect of the conspicuousness of the pore evaluated with the microscope (opening and a magnitude | size of a pore) by use of the formulation of Example 1 and Comparative Examples 1-3 is shown. The improvement rate of the conspicuousness of pores (opening / size of pores) evaluated with a microscope by using the preparations of Example 1 and Comparative Examples 1 to 3 is shown. The change of the score value used as the parameter | index of the improvement effect of the rough skin evaluated with the microscope by use of the formulation of Example 1 and Comparative Examples 1-3 is shown. The improvement rate of the rough skin evaluated with the microscope by use of the formulation of Example 1 and Comparative Examples 1-3 is shown. The change of the score value of the delamination which becomes a parameter | index of the rough skin improvement effect measured by the tape stripping method by use of the formulation of Example 1 and Comparative Examples 1-3 is shown. The improvement rate of the rough skin measured by the tape stripping method by use of the formulation of Example 1 and Comparative Examples 1-3 is shown.

Hereinafter, the present invention will be described in detail.
The composition for external use of the present invention is a composition comprising PQQ or a salt thereof and a peptide as active ingredients.

Since PQQ or its salt PQQ exists in various organisms such as animals, plants, and bacteria, it can be extracted from various organisms. Moreover, PQQ can purchase a commercial item.
Examples of the pharmaceutically acceptable salt of PQQ include alkali metal salts such as sodium salt, potassium salt, and lithium salt; and alkaline earth metal salts such as calcium salt and magnesium salt. Among the salts, sodium salt, potassium salt, calcium salt, and magnesium salt are preferable.

The content of PQQ or a salt thereof is preferably 0.00001% by weight or more, more preferably 0.0001% by weight or more, and still more preferably 0.001% by weight or more based on the total amount of the composition. If it is the said range, the effect of this invention mentioned above is fully acquired with the normal usage-amount of cosmetics or a quasi-drug.
In addition, the content of PQQ or a salt thereof is preferably 1% by weight or less, more preferably 0.3% by weight or less, and still more preferably 0.1% by weight or less with respect to the total amount of the composition. If it is the said range, the solubility in a formulation is favorable.

As the peptide peptide, a known peptide derived from a natural or synthetic source incorporated in cosmetics or quasi drugs can be used without limitation. Examples of such peptides include leguminous protein hydrolysates; silk protein hydrolysates; pearl protein hydrolysates; collagen hydrolysates (water-soluble collagen), low molecular collagen, collagen peptides, hydrolyzed collagen, atelocollagen, and Collagen derivatives such as succinyl atelocollagen; polypeptides such as (arginine / lysine) polypeptide; oligopeptide-6, decapeptide-2, tetrapeptide-21, tripeptide-3, diaminohydroxybutyric acid, palmitoyl dipeptide-5 diaminobuty Oligopeptides such as loyl hydroxythreonine, palmitoyl tripeptide-5, hexapeptide-2, hexapeptide-3, hexapeptide-9, heptapeptide-8, and hexanoyl dipeptide-3 norleucine acetate Tides; and dipeptides such as dipeptide-4, diacetic acid dipeptide diaminobutyroylbenzylamide, and palmitoyl dipeptide-5. Of these, leguminous plant protein hydrolysates are preferred.
A peptide can be used individually by 1 type or in combination of 2 or more types.

  The peak average molecular weight of the peptide is preferably 300 or more, more preferably 400 or more, and even more preferably 500 or more. Further, the weight average molecular weight of the legume hydrolyzate is preferably 10,000 or less, more preferably 5000 or less, and even more preferably 3000 or less. If it is the said range, the permeability | transmittance thru | or absorption from skin is good.

  In the present invention, the peak average molecular weight of a peptide is a value measured by a gel permeation chromatography (GPC) method, specifically, a value measured by the method described in Examples.

The content of the peptide is preferably 0.0001% by weight or more, more preferably 0.005% by weight or more, and still more preferably 0.001% by weight or more based on the total amount of the composition. If it is the said range, the effect of this invention will be fully acquired.
The peptide content is preferably 5% by weight or less, more preferably 1% by weight or less, and still more preferably 0.5% by weight or less, based on the composition. If it is the said range, it can suppress that a formulation emits the smell of a peptide, and precipitation of the peptide in a formulation.

The following legume protein hydrolyzate, described legume protein hydrolyzate.
Leguminous plant protein hydrolysates include, for example, whole leguminous plants (Leguminosase), protein hydrolysates such as roots, rhizomes, leaves, seeds, and stems, and broken or crushed materials thereof. It is. Among these, a hydrolyzate of seed protein is preferable. The protein may be a whole protein or a part of the protein.
Decomposition may be performed with an acid, an alkali, or an enzyme. Among them, an enzyme hydrolyzate is preferable and a protease hydrolyzate is more preferable in that the above-described effects of the present invention become remarkable and the treatment can be performed safely.

  Examples of the protease include serine protease, thermolysin, papain, bromelain, trypsin, chymotrypsin, pancreatin, and subtilin. Only one type of protease may be used, or two or more types may be used in combination. Among these, thermolysin is preferable in that the effect of the present invention described above is remarkably exhibited.

  Thermolysin (EC3.4.24.4) is a thermostable protease produced by the thermostable bacterium Bacillus thermoproteolytics and is commercially available from Daiwa Kasei Co., Ltd. Thermolysin is generally known to cleave peptide bonds on the amino group side of hydrophobic amino acid residues having large side chains (for example, isoleucine, leucine, valine, phenylalanine, methionine, and alanine). .

Leguminous plants include, for example, lentil plants (Lathyrus) such as L. japonicus and L. odoratus; pea plants (Pisum) such as P. sativum; Such as crow pea, V. angustifolia, broad bean (Vicia faba), sparrow pea (V. hirsuta), casmagusa (V. tetrasperma), vicia cracca, vicia dasycarpa, and vicia unijuga Broad bean plants (Vicia); Soybean plants such as soybean (Glycine max subsp. Soja); and Komatsunagi plants such as Komatsuagi.
Among them, spinach (Lathyrus), pea plant (Pisum), soybean genus plant, and Komatsuna genus plant are preferred, and among them, pea (L. japonicus), pea (P. sativum), soybean (Glycine max subsp. Max ), Peas (Glycine max subsp. Soja), and Komatsu eel (Indigofera pseudotinctoria) are more preferred, and peas, peas, soybeans, and peas are even more preferred.

Hereinafter, the soybean peptide will be described in detail. In the present invention, the soy peptide is a peptide of the genus Soybean. Of these, soybean peptide is preferable.
As for the site, it is preferable to use seeds of soybean genus plants. Seeds include whole seeds, moulted soybean seeds, defatted soybean seeds, snow flower vegetables (Okara) obtained from the whole seeds, and the like.

  The reaction conditions for degrading soy protein with a protease may be the optimum conditions for the protease. The optimum conditions for the protease can be appropriately selected by those skilled in the art based on common general technical knowledge. For example, when using a commercially available protease, the conditions described in the instruction manual may be adopted. As a specific example, soy protein or a soy protein concentration in a solvent such as water is generally 0.1 to 30% (w / v), preferably 1 to 10% (w / v). A raw material containing soy protein is suspended, and the suspension is generally 0.001 to 3% (w / v), preferably 0.01 to 0.125% (w / v). An embodiment in which a protease is added to perform a hydrolysis reaction is mentioned. The reaction time is generally 30 to 80 ° C, preferably 40 to 70 ° C, more preferably 50 to 60 ° C. The reaction time is generally 2 to 30 hours, preferably 3 to 24 hours, more preferably 10 to 20 hours, and still more preferably 12 to 18 hours. The pH of the reaction solution is preferably around the optimum pH of the protease to be used. For example, the pH when thermolysin is used is preferably 7 to 8.5.

Soy peptide is commercially available from, for example, Nisshin Oilio, ADM Far East, Showa Sangyo, and Fuji Oil.
The molecular weight of the soybean peptide is as described above for the peptide.

Peptide content ratio relative to PQQ or a salt thereof The peptide content ratio relative to PQQ or a salt thereof is preferably 0.001 part by weight or more with respect to 1 part by weight of PQQ or a salt thereof. More preferably, the content is 0.01 parts by weight or more, and still more preferably 0.1 parts by weight or more.
The content ratio of the peptide to PQQ or a salt thereof is preferably 1000 parts by weight or less, more preferably 300 parts by weight or less, with respect to 1 part by weight of PQQ or a salt thereof. It is even more preferable that the amount is not more than parts by weight.
If it is the said range, the effect of this invention will be fully acquired.

Thickener The composition of the present invention preferably contains a thickener. Thereby, the feeling of use becomes good, and the above-described effects of the present invention can be obtained more remarkably.
As a thickener, a well-known thing used as a thickener of cosmetics or a quasi-drug can be used without a restriction | limiting. Such known thickeners include, for example, cellulosic thickeners such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and carboxyethylcellulose; guar gum, locust bean Thickening polysaccharides such as gum, carrageenan and xanthan gum; dextran, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, alkyl methacrylate methacrylate copolymer, dextrin fatty acid ester, pectin, (hydroxyethyl acrylate / Acryloyldimethyltaurine Na) copolymer, dimethyl distearyl ammonium Ctrite, (acryloyldimethyltauronium ammonium / vinylpyrrolidone) copolymer, polyethylene glycol distearate, ethylene glycol triisostearate, polyoxyethylene (20) methylglucoside, polyisoethylene stearate, polyethylene glycol, bentonite, alginic acid, sodium alginate, propylene glycol alginate , Macrogol, sodium chondroitin sulfate, hyaluronic acid and salts thereof, and water-soluble polymers such as hyaluronic acid derivatives and salts thereof.
Among them, cellulose-based thickeners such as methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, and carboxyethylcellulose; guar gum, locust bean gum, Thickening polysaccharides such as carrageenan and xanthan gum; dextran, polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, alkyl methacrylate copolymer, dextrin fatty acid ester, pectin, (hydroxyethyl acrylate / acryloyl acrylate) Dimethyl taurine Na) copolymer, dimethyl distearyl ammonium hect And (acryloyldimethyltauronium ammonium / vinyl pyrrolidone) copolymer, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, xanthan gum, alkyl methacrylate copolymer More preferred are (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer and (acryloyldimethyltaurine ammonium / vinylpyrrolidone) copolymer.
A thickener can be used individually by 1 type or in combination of 2 or more types.

The content of the thickener is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, and still more preferably 0.05% by weight or more with respect to the total amount of the composition. If it is the said range, a favorable usability | use_condition can be obtained and the effect of this invention can fully be enhanced.
Further, the content of the thickener is preferably 5% by weight or less, more preferably 3% by weight or less, and still more preferably 2% by weight or less based on the total amount of the composition. If it is the said range, a thickener can be dissolved in a formulation.

Base or carrier Examples of the base or carrier include paraffin, liquid paraffin, squalane, white wax, gelled hydrocarbon (such as plastibase), ozokerite, ceresin, petrolatum, hard fat, microcrystalline wax, α-olefin oligomer, And hydrocarbons such as light liquid paraffin; fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and isostearic acid; glyceryl tri-2-ethylhexanoate (trioctanoin), and tri (capryl) Acid / capric acid) tri-fatty acid glycerides such as glyceryl; higher alcohols such as cetanol, stearyl alcohol, and behenyl alcohol; methyl polysiloxane, highly polymerized methyl polysiloxane, dimethyl siloxane methyl Oxyethylene) siloxane-methyl (polyoxypropylene) siloxane copolymer, dimethylsiloxane-methyl (polyoxyethylene) siloxane copolymer, dimethylsiloxane-methyl (polyoxypropylene) siloxane copolymer, polyoxyethylene-methylpoly Siloxane copolymer, poly (oxyethylene / oxypropylene) / methylpolysiloxane copolymer, dimethylsiloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, methyl acrylate copolymer Polysiloxane ester, crosslinked methylpolysiloxane, crosslinked methylphenylpolysiloxane, crosslinked polyether-modified silicone, crosslinked alkylpolyether-modified silicone, crosslinked alkyl-modified Silicone, decamethylcyclopentasiloxane, ethyltrisiloxane, methyltrimethicone, methylsiloxane network polymer, polyoxyethylene / methylpolysiloxane copolymer, methylhydrogenpolysiloxane, triethoxysilylethylpolydimethylsiloxyethylhexyl dimethicone, And silicone oils such as dimethylpolysiloxane; ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol diacetate, hexylene glycol diacetate, and 2-methyl-2-propene-1,1-diol Glycol acetates such as diacetate; triethylene glycol divalerate, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, and 2,2,4- Glycol esters such as limethyl-1,3-pentanediol diisobutyrate; ethylene glycol diacrylate, diethylene glycol diacrylate, propylene glycol monoacrylate, 2,2-dimethyl-trimethylene glycol diacrylate, and 1, Glycol acrylates such as 3-butylene glycol diacrylate; glycol dinitrates such as ethylene glycol dinitrate, diethylene glycol dinitrate, triethylene glycol dinitrate, and propylene glycol dinitrate; 2,2 '-[1,4 -Phenylenedioxy] diethanol; cellulose derivatives such as ethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose; polyvinyl Lorridone; carrageenan; polyvinyl butyrate; polyethylene glycol; dioxane; butylene glycol adipate polyester; isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and pentaerythritol tetra-2-ethylhexanoate Esters such as: dextrin and polysaccharides such as maltodextrin; lower alcohols such as ethanol and isopropanol; ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol mono Ethyl ether, diethylene glycol monopropyl ether, di Examples include glycol ethers such as ethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; and aqueous bases such as water.

Among them, hydrocarbons (particularly α-olefin oligomers, squalane, light liquid paraffin, and liquid paraffin), trifatty acid glycerides (particularly glyceryl tri-2-ethylhexanoate, and tri (caprylic / capric acid) glyceryl), higher grades Alcohol (especially cetanol, stearyl alcohol, and behenyl alcohol), silicone oil (especially methylpolysiloxane, alkyl acrylate copolymer methylpolysiloxane ester, cross-linked methylpolysiloxane, decamethylcyclopentasiloxane, ethyltrisiloxane, methyl Trimethicone, methylsiloxane network polymer, polyoxyethylene / methylpolysiloxane copolymer, methylhydrogenpolysiloxane, triethoxysilylethylpolydimethylsiloxyethylhexyl dimethyl ester And dimethylpolysiloxane), esters (especially isononyl isononanoate, and pentaerythritol tetra-2-ethylhexanoate), polysaccharides (especially dextrin and maltodextrin), glycol ethers (especially diethylene glycol monoethyl ether) ), As well as water.
A base or a support | carrier can be used individually by 1 type or in combination of 2 or more types.

Additives In the composition of the present invention, known additives that are added to cosmetics or quasi-drugs, for example, surfactants, preservatives, pH adjustments, as long as the effects of the present invention are not impaired. An agent, a chelating agent, a stabilizer, an irritation reducing agent, an antiseptic, a coloring agent, a dispersing agent, a fragrance, a pearly luster imparting agent, and the like can be added. An additive can be used individually by 1 type or in combination of 2 or more types.

  Examples of the surfactant include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate. Sorbitan fatty acid esters such as: glyceryl monostearate and glyceryl fatty acids such as glyceryl monostearate malate; polyglyceryl fatty acids such as polyglyceryl monostearate, polyglyceryl monoisostearate, and polyglyceryl diisostearate; monostearin Propylene glycol fatty acid esters such as propylene glycol acid; polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene Hydrogenated castor oil derivatives such as hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), and polyoxyethylene hydrogenated castor oil 80; polyoxyethylene (20) sorbitan monolaurate ( Polyoxyethylene, such as polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), and polyoxyethylene (20) sorbitan isostearate Sorbitan fatty acid esters; polyoxyethylene monococonut oil fatty acid glyceryl; glycerin alkyl ether; alkyl glucoside; polyoxyalkylene alkyl ether such as polyoxyethylene cetyl ether; Amines such as ruamine and oleylamine; and silicone-based surfactants such as polyoxyethylene-methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone. Can be mentioned.

  Among them, glycerin fatty acids (particularly glyceryl monostearate), polyglycerin fatty acids (particularly polyglyceryl monostearate), hardened castor oil derivatives (particularly polyoxyethylene hardened castor oil 50 (HCO-50)), and polyoxy Ethylene hydrogenated castor oil 60 (HCO-60)), polyoxyethylene sorbitan fatty acid esters (particularly polyoxyethylene (20) sorbitan isostearate and polyoxyethylene (20) sorbitan monostearate (polysorbate 60)), poly Oxyalkylene alkyl ethers (especially polyoxyethylene cetyl ether) and silicone surfactants (especially polyoxyethylene methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and P EG-9 polydimethylsiloxyethyl dimethicone) is preferred.

  Examples of preservatives or preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, Examples include benzyl paraoxybenzoate, methyl paraoxybenzoate, and phenoxyethanol. Of these, methyl paraoxybenzoate, propyl paraoxybenzoate, and phenoxyethanol are preferred.

  Examples of pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid, etc.), organic acids (lactic acid, acetic acid, citric acid, sodium citrate, tartaric acid, malic acid, succinic acid, succinic acid, etc. Acid sodium, oxalic acid, gluconic acid, fumaric acid, propionic acid, acetic acid, aspartic acid, epsilon-aminocaproic acid, glutamic acid, and aminoethylsulfonic acid), gluconolactone, ammonium acetate, inorganic base (sodium bicarbonate, carbonic acid) Sodium, potassium hydroxide, sodium hydroxide, calcium hydroxide, and magnesium hydroxide), and organic bases (such as monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, and lysine). Among these, succinic acid, sodium succinate, citric acid, sodium citrate, triethanolamine, potassium hydroxide, and sodium hydroxide are preferable.

Examples of the chelating agent include ethylenediaminetetraacetic acid (edetic acid), ethylenediaminetetraacetic acid salt (sodium salt (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium salt, etc.), phytic acid, gluconic acid, polyphosphorus An acid, metaphosphoric acid, etc. are mentioned. Of these, sodium edetate is preferable.
Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene, and butylhydroxyanisole.
Examples of the irritation reducing agent include licorice extract, sodium alginate, and 2-methacryloyloxyethyl phosphorylcholine.

Examples of the colorant include inorganic pigments and natural pigments.
Examples of the pearl luster imparting agent include ethylene glycol distearate, ethylene glycol monostearate, and triethylene glycol distearate. Of these, ethylene glycol distearate is preferable.

Other active ingredients The composition of the present invention includes, for example, an antioxidant component, an anti-aging component, an anti-inflammatory component, a whitening component, a keratin softening component, a cell activation component, and vitamins, as long as the effects of the present invention are not hindered. Other activities that can be added to cosmetics, such as blood circulation promoting ingredients, moisturizing ingredients, ingredients that prevent and / or repair DNA damage, UV absorbing ingredients, UV scattering ingredients, cleaning ingredients, antibacterial ingredients, and astringent ingredients Ingredients can be blended. Other active ingredients can be used singly or in combination of two or more.

  Examples of the antioxidant component include components derived from plants (eg, grape, ginseng, and comfrey); proanthocyanidins, tocopherol and derivatives thereof, ascorbic acid and derivatives thereof, hesperidin, glucosyl hesperidin, ergothioneine, hydrogen sulfite Examples include sodium, erythorbic acid and salts thereof, flavonoids, glutathione, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase, thioredoxin, taurine, thiotaurine, and hypotaurine. Among them, grape seed extract, grape leaf extract, ginseng extract, comfrey leaf extract, proanthocyanidins, tocopherol and its derivatives (particularly δ-tocopherol and α-tocopherol), ascorbic acid and its derivatives (particularly ascorbic acid, ascorbine) Sodium acid phosphate, magnesium ascorbate, and ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), hesperidin, glucosyl hesperidin, and ergothioneine are preferred.

  Antiaging components include, for example, hydrolyzed soy protein, retinoid (retinol and its derivatives, retinoic acid, retinal, etc.), pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivative, silicon, silicic acid, N-methyl -L-serine, mevalonolactone and the like. Of these, artemia extract, hydrolyzed soy protein, retinol, retinol acetate, and retinol palmitate are preferred.

  Anti-inflammatory components include, for example, components derived from plants (eg, Comfrey); allantoin, calamine, glycyrrhizic acid or derivatives thereof, glycyrrhetinic acid or derivatives thereof, zinc oxide, guaiazulene, pyridoxine hydrochloride, menthol, camphor, turpentine oil , Indomethacin, and salicylic acid or its derivatives. Of these, Comfrey leaf extract, allantoin, dipotassium glycyrrhizinate, and stearyl glycyrrhetinate are preferable.

  Examples of the whitening component include arbutin, hydroquinone, kojic acid, ellagic acid, phytic acid, lucinol, chamomile ET, ascorbic acid or a derivative thereof, vitamin E or a derivative thereof, pantothenic acid or a derivative thereof, tranexamic acid, and a whitening action. The plant component (for example, plant extract and essential oil) to have is mentioned. Among these, arbutin, hydroquinone, kojic acid, ascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, ascorbyl tetraisopalmitate (tetracordylhexyldecanoate) and tranexamic acid are preferable.

  Examples of the keratin soft component include lanolin, urea, phytic acid, lactic acid, lactate, glycolic acid, salicylic acid, malic acid, and citric acid. Of these, lactic acid, sodium lactate, glycolic acid, salicylic acid, and phytic acid are preferred.

  Examples of the cell activation component include components derived from plants (for example, bilberry); amino acids such as γ-aminobutyric acid and ε-aminoproic acid; retinol and derivatives thereof, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids Vitamins such as; α-hydroxy acids such as glycolic acid and lactic acid; tannins, flavonoids, saponins, allantoin, and photosensitizer 301. Among them, bilberry leaf extract, retinol, retinol acetate, and retinol palmitate are preferable.

  Vitamins include, for example, retinol, retinol derivatives (eg, retinol acetate, retinol palmitate), retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, d-δ-tocopheryl retinoate, α-tocotic acid Vitamin A such as ferryl retinoate and β-tocopheryl retinoate; provitamin A such as β-carotene, α-carotene, γ-carotene, δ-carotene, lycopene, zeaxanthin, cryptoxanthine, and echinone; δ Vitamin E's such as tocopherol, α-tocopherol, β-tocopherol, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, δ-tocopherol and tocopherol nicotinate; riboflavin, flavin mono Vitamin B2 such as creatide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, sodium riboflavin 5'-phosphate, and riboflavin tetranicotinate; methyl nicotinate, nicotinic acid, nicotinic acid amide, etc. Nicotinic acids; ascorbyl stearate, L-ascorbyl dipalmitate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, ascorbic acid phosphate Vitamin Cs such as ester magnesium and ascorbic acid glucoside; methyl hesperidin, ergocalciferol, and cholecalci Vitamin D such as ferrol; Vitamin K such as phylloquinone and farnoquinone; dibenzoyl thiamine, dibenzoyl thiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine Monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, and thiamine triphosphate monophosphate Vitamin B1 such as salts; Vitamin B6 such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'-pyridoxal phosphate, and pyridoxamine hydrochloride, cyanocobalamin, hydroxocobala And vitamin B12 such as deoxyadenosylcobalamin; folic acid such as folic acid and pteroylglutamic acid; pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantethein, D-panthetin, coenzyme A, And pantothenic acids such as pantothenyl ethyl ether; biotins such as biotin and biocytin; and vitamin-like agents such as carnitine, ferulic acid, α-lipoic acid, orotic acid, and γ-oryzanol.

  Among them, vitamin A such as retinol, retinol acetate, and retinol palmitate; ascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, and ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate) Vitamin Cs; vitamin Es such as δ-tocopherol and nicotinic acid tocopherol; and nicotinic acids such as nicotinamide are preferred.

  Examples of the blood circulation promoting component include plants (e.g., ginseng, ashitaba, arnica, ginkgo, fennel, enmelio, Dutch oak, chamomile, roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake, hawthorn, papaver, Senkyu, assembly, thyme, clove, chimpi, spruce, spruce, spruce, carrot, garlic, butcher bloom, grapes, buttons, maronier, melissa, yuzu, yokuinin, rosemary, rosehip, chimpi, spruce, spruce, peach, apricot , Walnuts, or corn); tocopherol nicotinate, glucosyl hesperidin, and hesperidin. Among these, ginseng extract, tocopherol nicotinate, glucosyl hesperidin, and hesperidin are preferable.

  Examples of the moisturizing component include components derived from plants (eg, Tigaya); amino acids such as alanine, serine, leucine, isoleucine, threonine, glycine, proline, hydroxyproline, glucosamine, and theanine and derivatives thereof; collagen, gelatin And proteins such as elastin, or hydrolysates thereof; polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, dipropylene glycol, and diglycerine; sugars such as sorbitol Phospholipids such as alcohol; lecithin, and hydrogenated lecithin; mucos such as hyaluronic acid, sodium hyaluronate, acetyl hyaluronic acid, sodium acetyl hyaluronate, heparin, and chondroitin NMF-derived components such as sugar; lactic acid, sodium pyrrolidone carboxylate, and urea; polyglutamic acid; a polymer having a phospholipid polar group such as MPC polymer (for example, LIPIDURE (registered trademark)); polyoxypropylene methyl glucoside; Examples thereof include trimethylglycine (betaine); hydroxyethylurea; acrylic acid / acrylamide / dimethyldiallylammonium chloride copolymer; and sorbitol. Among them, chigaya root extract, hydrolyzed collagen, hydrolyzed elastin, MPC polymer glycerin, 1,3-butylene glycol, polyethylene glycol, dipropylene glycol, diglycerin, polyoxypropylene methyl glucoside, trimethyl glycine (betaine), hydroxyethyl urea Acrylic acid / acrylamide / dimethyldiallylammonium chloride copolymer, hydrogenated lecithin, hyaluronic acid, sodium hyaluronate, acetyl hyaluronic acid, sodium acetyl hyaluronate, and sorbitol are preferred.

  Examples of components having an action of preventing and / or repairing DNA damage include, for example, components derived from animals (eg, Artemia); components derived from plants (eg, cat's claw); and DNA, DNA salts, RNA, and Examples include nucleic acid components such as RNA salts. Among these, artemia extract and DNA-Na are preferable.

  Examples of the ultraviolet absorbing component include 2-methoxyhexyl paramethoxycinnamate, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 2,4,6-tris [4- (2-ethylhexyl). Oxycarbonyl) anilino] -1,3,5-triazine, 2-ethylhexyl dimethoxybenzylideneoxoimidazolidinepropionate, and 2,4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] And -6- (4-methoxyphenyl) -1,3,5-triazine. Among them, 2-methoxyhexyl paramethoxycinnamate, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, and 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine is preferred.

  Examples of the ultraviolet scattering component include inorganic compounds such as zinc oxide, titanium oxide, iron oxide, cerium oxide, zirconium oxide, titanium silicate, zinc silicate, anhydrous silicic acid, cerium silicate, and hydrous silicic acid. Inorganic compounds coated with inorganic powders such as hydrous silicic acid, aluminum hydroxide, mica, talc, etc., and those inorganic compounds combined with resin powders such as polyamide, polyethylene, polyester, polystyrene, or nylon In addition, these inorganic compounds may be treated or coated with silicone oil or fatty acid aluminum salt. Among these, inorganic compounds such as zinc oxide, titanium oxide and iron oxide, inorganic powders such as aluminum hydroxide, hydrous silicic acid, mica or talc, or those treated or coated with silicone oil are preferable. .

  Examples of the cleaning component include polyoxyalkylene alkyl (or alkenyl) ether sulfate, alkyl (or alkenyl) sulfate, higher fatty acid salt, ether carboxylate, amide ether carboxylate, alkyl phosphate ester salt, N- Anionic surfactants such as acyl amino acid salts, polyoxyalkylene fatty acid amide ether sulfates, acylated isethionates, and acylated taurates; amine oxides, glycerin fatty acid esters, sorbitan fatty acid esters, alkyl saccharides, polyoxyalkylene alkyl ethers, Nonionic surfactants such as fatty acid alkanolamides and polyoxyalkylene hydrogenated castor oil; mono- or di-long-chain alkyls having linear or branched long-chain alkyl groups to which alkylene oxides may be added Cationic surfactants such as Le quaternary ammonium salts; as well as carboxymethyl betaine, sulfobetaine, imidazolinium betaine, and amphoteric surfactants such as amide betaine.

  Among these, anionic surfactants, nonionic surfactants, and amphoteric surfactants are preferable. Anionic surfactants include higher fatty acid salts (particularly salts of higher fatty acids such as palmitic acid, lauric acid, myristic acid and stearic acid), and N-acyl amino acid salts (particularly sodium N-lauroyl aspartate, hydroxylated). Potassium / N-coconut oil fatty acid potassium acylglutamate, coconut oil fatty acid acylglycine sodium, and myristoyl glutamic acid) are preferred. Among the nonionic surfactants, fatty acid alkanolamides (particularly, coconut oil fatty acid diethanolamide and coconut oil fatty acid monoethanolamide) and amine oxides (particularly, coconut oil alkyldimethylamine oxide and lauryldimethylamine oxide) are preferred. Amphoteric surfactants include imidazolinium betaines (particularly 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolium betaine and N-coconut oil fatty acid acyl-N-carboxymethoxyethyl-N-carboxymethylethylenediamine). Sodium) is preferred.

  Antibacterial components include, for example, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cresol, gluconic acid and its derivatives, popidone iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer No. 101, Photosensitizer 201, Paraben, phenoxyethanol, 1,2-pentanediol, and alkyldiaminoglycine hydrochloride. Among them, benzalkonium chloride, benzethonium chloride, gluconic acid and its derivatives, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101, photosensitizer 201, paraben, phenoxyethanol, 1,2-pentanediol, and alkyldiamino hydrochloride Glycine is preferred, and benzalkonium chloride, gluconic acid and its derivatives, benzethonium chloride, and isopropylmethylphenol are more preferred.

  Examples of astringent components include metal salts such as alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, zinc sulfate, and potassium aluminum sulfate; and organic acids such as tannic acid, citric acid, lactic acid, and succinic acid be able to. Among these, alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, potassium aluminum sulfate, and tannic acid are preferable.

The composition of this invention can be prepared by mixing and stirring each component according to a conventional method.
pH
4-8 are preferable and, as for pH of the composition of this invention, 5-7 are more preferable. If it is the said range, it will become a stable formulation by which isolation | separation of the composition and decomposition | disassembly of the component were suppressed.

Formulation Form The form of the composition of the present invention is not particularly limited, and can take a form known as a cosmetic or quasi-drug form. As such known forms, for example, liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, aerosols, powders, poultices, nonwoven fabrics and the like are impregnated with chemicals. And a stick agent such as a lipstick. Of these, liquids, suspensions, emulsions, creams, ointments, gels, and lotions are preferred, and liquids, emulsions, creams, gels, and lotions are more preferred in terms of good usability.
Further, the specific use of the cosmetic composition is not particularly limited. For example, foundations such as lotion, milky lotion, cream, cosmetic liquid, sunscreen cosmetics, packs, hand creams, body lotions, and body creams. Cosmetics; cleansing cosmetics such as facial cleansers, makeup removers, body shampoos, shampoos and rinses; makeup cosmetics such as foundations, makeup bases, lip balms, lipsticks and teak colors; and bathing agents Can be mentioned.

In-use mixed composition The composition of the present invention is a mixed-in-use or in-use prepared type comprising a first composition containing PQQ or a salt thereof and a second composition containing a peptide. It can be set as a composition for external use. The present inventor has found that PQQ or a salt thereof is easily degraded or denatured in the presence of a peptide, and includes a first composition containing PQQ or a salt thereof and a second composition containing a peptide. By mixing at the time of use, it is avoided that the physiological activity of PQQ or a salt thereof is reduced or lost during storage or distribution.

Container The composition of the present invention can be used by being contained in a container having a shape and material appropriately selected according to the purpose and application of use. Examples of the container shape include a bottle type, a tube type, a jar type, a spoid type, a dispenser type, a stick type, a pouch bag, and a cheer pack. Examples of the material include polyethylene terephthalate, polypropylene, polyethylene (such as HDPE, LDPE, and LLDPE), ABS resin, ethylene vinyl alcohol resin, polystyrene, glass, and metal (such as aluminum). In addition, these materials are subjected to various coating treatments in consideration of strength, flexibility, weather resistance, component stability, etc., and these materials are combined or laminated, for example, by mixing them. It can be used as a container material. Moreover, those skilled in the art can select the diameter of the nozzle of the container and the elution part of the preparation and the material in order to limit the discharge amount from the container and reduce the adhesion to the container.

  Moreover, when setting it as a mixing type composition at the time of use, the container which accommodates a 1st agent and the container which accommodates a 2nd agent can make discharge parts, such as a nozzle, common. Moreover, the discharge part of each container may become one from the middle, a 1st agent and a 2nd agent may be mixed there, and a mixture may be finally discharged from one container opening. Moreover, the discharge part and container port of the container which accommodates the 1st agent, and the discharge part and container port of the container which accommodates the 2nd agent are separate, and a user mixes both agents after taking on a hand or skin. It may be a thing.

Method of Use The method of using the composition of the present invention varies depending on the skin condition, age, sex, etc. of the subject of use, but may be the following method, for example. That is, an appropriate amount (for example, 0.05 to 5 g) may be applied to the skin several times a day (for example, 1 to 5 times, preferably 1 to 3 times). Further, the daily use amount of PQQ or a salt thereof is, for example, 0.0005 to 0.05 g, preferably 0.001 to 0.02 g, more preferably 0.002 to 0.01 g, or What is necessary is just to apply | coat a composition so that the daily usage-amount will be 0.01-1g, for example, Preferably it is 0.02-0.4g, More preferably, it is 0.04-0.2g.
The application period may be, for example, 2 weeks to 6 months, preferably 1 to 6 months.

  In the case of a mixed composition at the time of use, the mixture of the first agent and the second agent may be discharged from the container mouth, and the mixture may be spread on the skin, or the first agent and the second agent. May be spread out while being mixed on the hand or on the skin to which the composition of the present invention is applied after each is discharged from a separate container mouth. Alternatively, after applying one agent to the skin and allowing it to blend, the other agent may be applied to the skin and blended.

The usage ratio of the first agent containing PQQ or a salt thereof and the second agent containing a peptide is such that the amount of peptide used is 0.001 part by weight or more, particularly 0. It is preferable that the amount be 01 parts by weight or more, and particularly 0.1 parts by weight or more.
Moreover, the usage ratio of the 1st agent containing PQQ or its salt and the 2nd agent containing a peptide is the usage-amount of a peptide with respect to 1 weight part of PQQ or its salt. It is preferable that the amount be 100 parts by weight or less.
If it is the said range, the effect of this invention will be fully acquired.

  The composition for external use of the present invention can be suitably used for people having various skin diseases and skin troubles in anticipation of the physiological activity of PQQ or a salt thereof and a peptide. Particularly suitable are persons who have large pores or deep pores, who are conspicuous, those who have wrinkles, those whose skin texture is disturbed, and those who have sensitive skin. Moreover, the person who has normal skin also becomes a suitable use object for prevention of a skin trouble.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these Examples.

(1) Preparation of composition
Reference example (preparation of soybean protein hydrolyzate)
50 g of powdered separated soybean protein (product name “PR-800”, manufactured by Daiwa Kasei Co., Ltd.) was dispersed in 2 L of distilled water and adjusted to pH 8.0 with 0.1 N NaOH. 500 mg of thermolysin (derived from Bacillus thermoproteolyticus, product name “Samorose PC10F”, manufactured by Daiwa Kasei Co., Ltd.) was added, and degradation was performed at 60 ° C. for 15 hours. After the reaction, the thermolysin was inactivated by boiling at 100 ° C. for 10 minutes. After allowing to cool, 25 g of filter aid (Radiolite 500, Showa Chemical Industry Co., Ltd.) was added and stirred, followed by filtration. The obtained filtrate was concentrated under reduced pressure to 500 mL and then freeze-dried to finally obtain 26 g of thermolysin hydrolyzate.

Measurement of peak average molecular weight of soybean protein hydrolyzate The peak average molecular weight of the hydrolyzate thus obtained was measured by the GPC method.
Soybean peptide was dissolved in 25 mM Tris-HCl buffer (containing 150 mM NaCl, pH 7.5) to prepare a 1 mg / mL test solution. HPLC column Superdex peptide HR (10 mm ID × 30 cm, manufactured by Amersham Biosciences) was equilibrated with the same buffer, and 100 μL of the test solution was injected into this column. The flow rate of the column was 0.5 mL / min, the column temperature was room temperature, the peptide was detected at 214 nm, and the molecular weight distribution and peak average molecular weight were estimated from the elution time. In addition, as peptide preparations with known molecular weights, Cytochrome C (Sigma, molecular weight 12327), Aprotinin (Sigma, molecular weight 6518), Hexaglycine (Sigma, molecular weight 360), Triglycine (Sigma, molecular weight 189) Glycine (manufactured by Sigma, molecular weight 75) was used.
Peptides were detected at 214 nm, and molecular weight distribution and peak average molecular weight were estimated from the elution time. As a result, the peak average molecular weight of the thermolysin hydrolyzate of soybean protein obtained in this example was 711.
In the present specification, “peak average molecular weight” is an average molecular weight measured by the GPC method under the above conditions, and means a molecular weight corresponding to the elution time of the peak top (the strongest peak) of the chromatogram.

Using the soybean protein hydrolyzate prepared as described above, an external composition having the following composition was prepared.
Example 1 (milky lotion)
First soy protein hydrolyzate 0.2
Sorbitan monostearate0.6
Polyoxyethylene sorbitan isostearate (20.EO.) 0.8
Carboxyvinyl polymer 0.2
1,3-butylene glycol 3
Dipropylene glycol 3
Sodium edetate 0.05
Behenyl alcohol 0.3
Stearyl alcohol 0.4
Tri (Capryl / Capric Acid) Glyceryl 4
Alpha olefin oligomer 8
Tri (capryl / caprin / myristin / stearic acid) glyceride 0.5
pH adjuster appropriate amount preservative appropriate amount purified water remaining second agent PQQ2Na 0.02
Acrylic acid / alkyl methacrylate copolymer 0.4
Polyglyceryl monostearate0.2
Liquid paraffin 5
Sodium edetate 0.05
pH adjuster Appropriate amount of preservative Appropriate amount of purified water Remaining amount The first agent and the second agent were prepared and stored in glass containers, respectively.

Example 2 (Gel lotion)
First soy protein hydrolyzate 0.3
Polyoxyethylene sorbitan isostearate (20. EO.) 0.6
Carboxyvinyl polymer 0.15
Hydroxyethyl cellulose 0.1
Dipropylene glycol 3
Glycerin 5
Sodium edetate 0.05
Tri (capryl / capric) glyceryl 3
pH adjuster Appropriate amount Preservative Appropriate amount of purified water Remaining second agent PQQ2Na 0.3
Carboxyvinyl polymer 0.2
Dipropylene glycol 5
Sodium edetate 0.05
pH adjuster Appropriate amount Preservative Appropriate amount of purified water Remaining 1st agent and 2nd agent are prepared respectively, 2 agent mixed type pump container (material of container body, pump head part, dispenser part; polypropylene, 0.3 push per push) Housed in.

Example 3 (Gel serum)
First soy protein hydrolyzate 0.05
Sorbitan monoisostearate0.4
Polyoxyethylene sorbitan isostearate (20. EO.) 0.4
Carboxyvinyl polymer 0.3
Xanthan gum 0.05
Dipropylene glycol 3
Glycerin 5
Sodium edetate 0.05
Sodium hyaluronate 0.1
Behenyl alcohol 0.2
Stearyl alcohol 0.3
Tri (capryl / capric) glyceryl 3
pH adjuster appropriate amount preservative appropriate amount purified water remaining second agent PQQ2Na 0.1
Acrylic acid / alkyl methacrylate copolymer 0.35
1,3-butylene glycol 5
Sodium edetate 0.05
pH adjuster Appropriate amount Preservative Appropriate amount of purified water Remaining 1st agent and 2nd agent are prepared, respectively. Container body material: Polyethylene terephthalate, Dispenser part material: Polypropylene, 1 push 0.3mL dispenser container Each housed.

Example 4 (milk emulsion x gel serum)
First soy protein hydrolyzate 0.1
Sorbitan monostearate 0.6
Polyoxyethylene sorbitan isostearate (20.EO.) 0.8
Carboxyvinyl polymer 0.2
1,3-butylene glycol 3
Dipropylene glycol 3
Soy hydrolyzate 0.01
Sodium edetate 0.05
Behenyl alcohol 0.3
Stearyl alcohol 0.4
Tri (Capryl / Capric Acid) Glyceryl 4
Alpha olefin oligomer 8
Tri (capryl / caprin / myristin / stearic acid) glyceride 0.5
pH adjuster appropriate amount preservative appropriate amount purified water remaining second agent PQQ2Na 0.01
Acrylic acid / alkyl methacrylate copolymer 0.4
Polyglyceryl monostearate0.2
Liquid paraffin 5
Sodium edetate 0.05
pH adjuster Appropriate amount Preservative Appropriate amount of purified water Remaining 1st agent and 2nd agent are prepared respectively, 2 agent mixed type pump container (material of container body, pump head part, dispenser part; polypropylene, 0.4 push per push) Housed in.

Example 5 (cream)
First soy protein hydrolyzate 0.05
Sorbitan monostearate1.2
Polyoxyethylene sorbitan isostearate (20. EO.) 1.2
Carboxyvinyl polymer 0.2
Pullulan 0.2
Hydrolyzed collagen 0.05
Hydroxyethyl cellulose 0.05
1,3-butylene glycol 10
Glycerin 10
Sodium edetate 0.05
Behenyl alcohol 2
Tri (Capryl / Capric Acid) Glyceryl 8
Jojoba oil 5
Tri (capryl / caprin / myristin / stearic acid) glyceride 3
pH adjuster Appropriate amount Preservative Appropriate amount of purified water Remaining second agent PQQ2Na 0.3
Acrylic acid / alkyl methacrylate copolymer 0.1
Xanthan gum 0.05
Polyglyceryl monostearate 1.5
Glycerol monostearate2.1
1,3-butylene glycol 3
Glycerin 5
Dipropylene glycol 2
Sodium edetate 0.05
Behenyl alcohol 1.5
Cetanol 1.5
Squalane 5
Glyceryl tri-2-ethylhexanoate 5
Shea fat 2
pH adjuster Appropriate amount Preservative Appropriate amount of purified water Remaining 1st agent and 2nd agent are prepared respectively, 2 agent mixed type pump container (material of container body: polyethylene terephthalate, material of pump head / pump part: polypropylene, 1 Push 0.5 mL).

Example 6 (cream)
First soy protein hydrolyzate 0.3
Glycerol monostearate1.6
Polyglyceryl monostearate2.0
Xanthan gum 0.1
1,3-butylene glycol 5
Glycerin 5
Dipropylene glycol 2
Sodium edetate 0.05
Behenyl alcohol 2
Squalane 5
Glyceryl tri-2-ethylhexanoate 5
Tri (capryl / caprin / myristin / stearic acid) glyceride 3
pH adjuster Appropriate amount Preservative Appropriate amount of purified water Remaining second agent PQQ2K 0.01
Acrylic acid / alkyl methacrylate copolymer 0.2
Xanthan gum 0.1
Sorbitan monostearate1.2
Polyoxyethylene sorbitan isostearate (20. EO.) 1.2
1,3-butylene glycol 3
Glycerin 5
Dipropylene glycol 2
Sodium edetate 0.05
Behenyl alcohol 2
Tri (Capryl / Capric Acid) Glyceryl 8
Jojoba oil 5
pH adjuster Appropriate amount Preservative Appropriate amount of purified water Remaining 1st agent and 2nd agent are prepared respectively, 2 agent mixed type pump container (material of container body: polyethylene terephthalate, material of pump head / pump part: polypropylene, 1 Push 0.5 mL).

(2) Test 1
(2-1) Test method 28 male and female panels aged 30 to 44 years took appropriate amounts of both agents of Example 1 on an equal volume of palm twice a day for 56 days, mixed with palms, and then applied to the entire face. . Skin image analysis (VISIA), stratum corneum moisture content measurement, and questionnaire survey were performed at the start of application (0 w), 28 days after the start of application (4 w), and 56 days after the start of application (8 w). Measurements and questionnaire surveys were conducted after the face was stabilized for about 10 minutes.

Details of the measurement method are as follows.
(i) Skin image analysis imaging site: 1) Right side 2) Left side Device used: VISIA Evolution / Integral analysis: Analysis was performed with analysis software of VISIA internal organs.
1) Evaluation of pore improvement
2) Evaluation of wrinkle improvement
3) Evaluation of texture improvement For pores, the size (area), color value (depth of pores) and number of pores, for wrinkles the length / width and color value of wrinkles, and for texture on the skin surface The area connecting the points where the skin grooves meet was evaluated by the numerical value processed by the internal organ software. The numerical values before and after the application are compared, and the effect is stronger as the degree of decrease in the numerical value after the application than before the application is larger.

(ii) Keratin Moisture Moisture Measurement Measurement site: right cheek Measuring instrument: CORNEOMETER AM825, SKICON-200EX / Integral

(iii) Questionnaire survey A questionnaire was carried out on 28 panels to which the composition for external use was applied at the start of the test (before application), 4 weeks later, and 8 weeks later, and comments regarding skin quality improvement were confirmed. The questionnaire items are “dullness”, “glossy”, “texture (irregularities of pores)”, “fine lines in the corners of the eyes”, “depth of wrinkle lines”, “moisture”, and “total skin condition”. Item. Each item is evaluated on a 10-point scale. A score of 0 indicates the worst state, and a score of 10 indicates the best state. If the skin condition in each item is neither good nor bad, the score is 5.

(2-2) Results FIGS. 1 to 5 show changes in the respective evaluation values due to the use of the composition of Example 1 for 4 weeks.
FIG. 1 shows changes in evaluation values of improvement scores (size and dents) of pores, and FIG. 2 shows changes in the number of pores per area specified in the range. FIG. 3 shows the change in the evaluation value of wrinkles, FIG. 4 shows the change in the evaluation value of texture (change in the area connecting the points where the skin grooves meet on the skin surface), and FIG. The change value of the evaluation value of quantity is shown.
FIG. 6 shows measurement images of the number of pores before using the preparation of Example 1 and after 8 weeks of use. FIG. 7 shows measurement images of texture (number of irregularities in pores) before using the preparation of Example 1 and after 8 weeks of use.

(i) Skin image analysis The improvement status of pores, wrinkles, and texture is superior to the situation before application by applying the composition for external use of the present invention. Improved. That is, with respect to the pores, it was shown that the size and the dent of the pore portion were reduced, and the high effect of the external composition of the present invention was confirmed.

(ii) Measurement of stratum corneum moisture The amount of stratum corneum was significantly increased by applying the composition for external use of the present invention.

(iii) The results of the questionnaire survey are shown in Table 1 and Table 2 below. As for the questionnaire results, for each item, the results of the monitor whose score before application is less than or equal to a score of 5 “state is neither good nor bad” were tabulated. In addition, “improvement” in the table indicates the number of monitors (monitors in which the effect was felt by application) whose post-administration score (improvement effect) is higher than that before administration (0w), and “no improvement” The number of monitors with the same pre-dose score and post-dose score is shown. In this test, there was no monitor in which the composition of Example 1 was applied, resulting in a score lower than the pre-application score (state deteriorated).

(3) Test 2
(3-1) Test method In the preparation of Example 1 above, an external composition in which PQQ2Na was replaced with water (Comparative Example 1), an external composition in which soybean protein hydrolyzate was replaced with water (Comparative Example 2), and A composition for external use (Comparative Example 3) in which PQQ2Na and soybean protein hydrolyzate were replaced with water was prepared.
Twenty-four male and female panels 25 to 50 years old, twice a day for 28 days, take an appropriate amount of the first agent and the second agent of Example 1 in the palm of their hands and mix them with their palms. It was applied to the entire right half (n = 24). The 24 persons were divided into 3 groups, and the preparations of Comparative Example 1, Comparative Example 2, and Comparative Example 3 were applied to the left half of the face of 8 persons in each group (n = 8). In Comparative Examples 1 to 3, the first agent and the second agent were applied in an appropriate amount so as to have an equal volume on the palm and mixed with the palm.
Skin image analysis 1 (Robo Skin Analyzer), skin image analysis 2 (microscope), and stratum corneum tape stripping were performed at the start of application (0 w) and 28 days after the start of application (4 w). The measurement was performed after the face was washed and the state was stabilized for about 10 minutes. Table 3 below shows the presence or absence of PQQ2Na and soybean protein hydrolyzate in the composition of each example used in the test.

Details of the measurement method are as follows.
(i) Skin image analysis 1
Imaging site: 1) Right side 2) Left side Device used: Robo Skin Analyzer CS50 / Neek Analysis: Analysis was performed using the analysis software of the internal organs of the device.
With respect to the pores, the size (area) and number of pores were evaluated by numerical values processed with the internal organ software. The effect of the present invention was confirmed by comparing numerical values before the start of the test (0 w) and 4 weeks after the application (4 w).

(ii) Skin image analysis 2
Imaging part: 1) Right cheek (center and bottom) 2) Left cheek (center and bottom)
Equipment used: Microscope / Keyence Analysis method: The skin was photographed with a microscope before and 4 weeks after the start of the test. The photographed images are visually evaluated based on the following evaluation criteria. (A) Pore conspicuousness (openness / size of pores) before test start (0w) and 4 weeks later (4w), and (b) skin The state (rough skin) was calculated.
(a) Pore conspicuous evaluation score Grade 5: Pore is inconspicuous Grade 4: Pore is almost inconspicuous Grade 3: Pore is slightly conspicuous Grade 2: Pore is conspicuous Grade 1: Extremely conspicuous pore is conspicuous
(b) Evaluation score of skin condition (rough skin) Score 5: Skin groove is clearly visible or clean mesh score 4: Skin groove is recognized or slightly meshed Score 3: Skin groove is recognized However, it is shallow or strong in one direction. Score 2: Skin groove is slightly blurred or strong in one direction. Score 1: Skin groove is unclear.

(iii) Exfoliation site of stratum corneum tape : 1) Right cheek (center and bottom) 2) Left cheek (center and bottom)
Analysis method: The stratum corneum collected with cellophane tape from the cheek was transferred to a slide glass, and stained with gentian violet-brilliant green to stain the stratum corneum. It observed with the optical microscope and evaluated visually based on the following evaluation criteria, and calculated (c) delamination (skin roughness) degree before test start (0w) and after 4 weeks (4w).
(c) Evaluation score of exfoliation of stratum corneum 1: High Evaluation 2: Slightly high Evaluation 3: Medium Evaluation 4: Slightly low Evaluation 5: Low A high score value of exfoliation of stratum corneum indicates a good skin environment, A low score value indicates that the skin environment (skin roughness) is poor. For this reason, when it goes from a low value to a high value (score difference is positive), it indicates that the rough skin has been improved, and when it is from a high value to a low value (score difference is negative), it indicates that the rough skin has deteriorated.

(3-2) Results FIGS. 8 to 15 and Tables 4 to 9 show changes in the respective evaluation values due to the use of the compositions of Example 1 and Comparative Examples 1 to 3 for 4 weeks.
FIG. 8 and Table 4 show the rate of change in the number of pores per area specified in the range after application for 4 weeks (4 W) relative to before application (0 W).
FIG. 9 and Table 5 show the change rate of the pore area per area designated in the range after application for 4 weeks (4 W) with respect to before application (0 W).
FIG. 10 and Table 6 show score values that serve as an index of the effect of improving the conspicuousness of pores (openness / size of pores) evaluated with a microscope. FIG. 11 and Table 7 show the improvement rate after 4 weeks of application (4 W) with respect to the noticeability of pores (openness / size of pores) evaluated with a microscope, compared to before application (0 W).
FIG. 12 and Table 8 show score values that are indicators of the effect of improving rough skin evaluated with a microscope. FIG. 13 shows the improvement rate after 4 weeks of application (4 W) versus before application (0 W) of rough skin evaluated with a microscope.
FIG. 14 and Table 9 show the score values of delamination as an index of the effect of improving skin roughness, measured by a tape stripping method. FIG. 15 shows the improvement rate after 4 weeks of application (4 W) versus before application (0 W) of rough skin as measured by the tape stripping method.

(i) Skin image analysis 1
As apparent from FIGS. 8 to 9 and Tables 4 to 5, by applying the composition for external use of the present invention, the condition of the pores after administration was significantly improved.

That is, Example 1 combining PQQ2Na and soy protein hydrolyzate reduced the number of pores to 95% compared to the initial value, and a synergistic effect was observed in the decrease in the number of pores. The number of pores as a result of the decrease in Example 1 was about 50 per half face.
Moreover, Example 1 which combined PQQ2Na and soybean protein hydrolyzate reduced the pore area, and the synergistic effect was recognized by the reduction | decrease of a pore area.
These results indicate that the size and the dent of the pore portion are reduced, and a high effect of pore reduction by the external composition of the present invention was confirmed.

(ii) Skin image analysis 2
<Improves conspicuous pores (opening / size of pores)>
As is apparent from FIGS. 10 to 11 and Tables 6 to 7, the conspicuousness of pores (openness / size of pores) was significantly improved by applying the composition for external use of the present invention.

The composition for external use of Example 1 combining PQQ2Na and soybean protein hydrolyzate greatly increased the score value and the improvement rate, and a synergistic effect was observed in improving the conspicuousness of pores.
That is, in the composition for external use of the present invention, the conspicuous score value after 4 weeks of application of Example 1 showed a score of 3.8, which was a score comparable to “almost no pores were conspicuous: score 4”.
The increase in the score value of the conspicuous pores and the improvement rate indicates that the size of the pores and the dents were reduced, and the high effect of pore reduction by the external composition of the present invention was confirmed.

<Improves rough skin>
As apparent from FIGS. 12 to 13 and Table 8, rough skin was significantly improved by applying the composition for external use of the present invention. That is, the external composition of the present invention significantly improved the clarity of the skin groove after 4 weeks of application.
That is, Example 1 combining PQQ2Na and soy protein hydrolyzate greatly increased the score value and the improvement rate, and a synergistic effect was observed in improving rough skin. That is, the score value before administration of Example 1 was 1.5 (rough skin state), while the score value after administration was 2.9. It can be seen that rough skin has improved.

(iii) Keratin tape stripping The stratum corneum peeling test is one of the indices for evaluating rough skin.
As apparent from FIGS. 14 to 15 and Table 9, as a result of the multi-layer peeling test, the exfoliation of the stratum corneum was significantly reduced by applying the composition for external use of the present invention. It was shown that rough skin improved.
Score difference indicator
-2: worsening, -1: no change, 0: no change, 1: slight improvement, 2: improvement

  That is, Example 1 combining PQQ2Na and soy protein hydrolyzate greatly increased the score value and the improvement rate (score difference was 0.71), and a synergistic effect was observed in improving rough skin. The score difference of Example 1 of 0.71 is close to the score difference of 1 “slightly improved skin roughness”, and the improvement effect is clearly higher than those of Comparative Examples 1 to 3.

  The composition for external use of the present invention effectively improves rough skin, improves wrinkles, smoothes the skin, improves skin smear, gives gloss, has excellent moisture retention, makes pores smaller or conspicuous Therefore, it is useful as a cosmetic or quasi-drug.

Claims (22)

A composition for external use comprising pyrroloquinoline quinone or a pharmaceutically acceptable salt thereof, and a soybean protein protein hydrolyzate as active ingredients. Further, the external composition of claim 1 containing a water-soluble polymeric thickening agent. The external composition of Claim 1 or 2 which contains 0.00001-1 weight% of pyrroloquinoline quinone or its pharmaceutically acceptable salt with respect to the whole quantity of a composition. Soybean genus vegetable protein hydrolyzate, based on the total amount of the composition, the composition for external use according to any one of claims 1 to 3 containing 0.0001 wt%. The composition for external use according to any one of claims 1 to 4 , comprising 0.001 to 1000 parts by weight of a soybean plant protein hydrolyzate with respect to 1 part by weight of pyrroloquinoline quinone or a pharmaceutically acceptable salt thereof. . Any one of Claims 1-5 which is a composition at the time of use provided with the composition containing the pyrroloquinoline quinone or its pharmaceutically acceptable salt, and the composition containing a soybean genus plant protein hydrolyzate. A composition for external use according to the above. A pore shrinkage agent comprising the composition for external use according to any one of claims 1 to 6 . The rough skin improving agent which consists of an external composition in any one of Claims 1-6 . A skin texture improving agent comprising the composition for external use according to any one of claims 1 to 6 . The wrinkle improving agent which consists of a composition for external use in any one of Claims 1-6. The improvement agent of the barrier function of the skin which consists of an external composition in any one of Claims 1-6. A skin moisture content improver comprising the composition for external use according to any one of claims 1 to 6. An agent for improving skin skin, comprising the composition for external use according to any one of claims 1 to 6. A skin gloss improving agent comprising the composition for external use according to any one of claims 1 to 6. (A) preparing a soybean plant protein hydrolyzate, and
(B) A step of preparing a composition for external use using pyrroloquinoline quinone or a pharmaceutically acceptable salt thereof, and a soybean plant protein hydrolyzate prepared in step (A).
The manufacturing method of the composition for external use containing this. The production method according to claim 15, wherein the soybean plant protein hydrolyzate is a hydrolyzate of soybean plant protein with a protease. The production method according to claim 16, wherein the protease is thermolysin. The manufacturing method according to any one of claims 15 to 17, wherein in the step (B), a composition for external use is further prepared using a water-soluble polymer thickener. The composition for external use is prepared such that in step (B), pyrroloquinoline quinone or a pharmaceutically acceptable salt thereof is contained in an amount of 0.00001 to 1% by weight based on the total amount of the composition. The manufacturing method in any one. The composition for external use according to any one of claims 15 to 19, wherein in the step (B), the composition for external use is prepared so as to contain 0.0001 to 5 wt% of the soybean protein hydrolyzate with respect to the total amount of the composition. Production method. In step (B), a composition for external use is prepared such that the hydrolyzate of soybean plant protein is 0.001 to 1000 parts by weight with respect to 1 part by weight of pyrroloquinoline quinone or a pharmaceutically acceptable salt thereof. The manufacturing method according to any one of claims 15 to 20. (B) The composition for external use prepared in the step comprises a composition containing pyrroloquinoline quinone or a pharmaceutically acceptable salt thereof, and a composition containing a soybean genus plant protein hydrolyzate. It is a formula composition, The manufacturing method in any one of Claims 15-21.