JP2000159656A - Agent for promoting synthesis of collagen - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare an agent for promoting the synthesis of collagen, having collagen synthesis-accelerating effect excellent in stability and capable of providing cosmetics excellent in wrinkle-improving effect by including a specific ascorbic acid (derivative), a nonionic surfactant and neutral fat. SOLUTION: This agent for promoting the synthesis of collagen is prepared by including (A) 1-70 wt.% L-ascorbic acid or its derivative (e.g. L-ascorbyl-2- phosphate) each in a state of ultra fine particles having <=3 μm (preferably <=1 μm, more preferably <=0.5 μm) average particle diameter preferably subjected to physical crushing, (B) a nonionic surfactant (e.g. polyglycerin-condensed ricinolein) preferably having <=4 HLB in a 1-100 wt.% bases on the quantity of the ingredient C and (C) a neutral fat (e.g. a triglyceride of a fatty acid having a medium-sized chain) preferably having <=45 deg.C melting point (more preferably having a melting point lower than room temperature) in a W/O form where the ingredient A is dispersed in the ingredients B and C.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to at least one member selected from the group consisting of L-ascorbic acid and derivatives thereof.
Collagen synthesis promoter containing a seed (hereinafter referred to as L-ascorbic acid) as a physiologically active ingredient and skin cosmetics (including quasi-drugs and medicinal cosmetics containing the same; hereinafter the same). Things.

[0002]

2. Description of the Related Art L-ascorbic acids have been used for a wide range of applications as nutrients for pharmaceuticals, cosmetics and foods or as antioxidants due to their unique physiological actions. In particular, whitening for the purpose of preventing and treating skin spots and freckles, etc., utilizing the melanin production inhibitory effect of epidermal melanocytes, the inflammation inhibitory effect by ultraviolet rays, and the collagen production promotion effect of dermal fibroblasts possessed by L-ascorbic acids. It is widely used in cosmetics and anti-aging cosmetics for the purpose of preventing wrinkles and moisturizing the skin. However, L-ascorbic acids, as typified by L-ascorbic acid, have the disadvantage of being unstable to oxidation, heat and light.

[0003] As a method of stabilizing L-ascorbic acid,
Esterification with fatty acids (JP-B-55-45546, etc.), phosphate esterification and complexation (Japanese Patent Laid-Open No. 7-53581)
), Or a method in which an amino acid or an organic acid is used in combination as a stabilizer (for example, Japanese Patent Publication No. 57-480).
50) have been proposed. However, the above L-
The storage stability of ascorbic acid and its derivatives is still insufficient or cannot withstand heat sterilization, so that when applied to the skin, sufficient effects cannot be obtained and the effect of promoting collagen synthesis is not sufficiently recognized. There were many things. Further, these derivatives have a problem that the pharmacological effect of L-ascorbic acid is reduced and side effects occur.

When an amino acid or an organic acid is used in combination as a stabilizer, ammonia and the like are generated depending on the oxidation state of L-ascorbic acid itself and pH conditions, and there is a problem that the smell has an undesirable effect on use. .

In addition, a method of mixing L-ascorbic acid and a simple salt thereof with a mixture of an oil and fat having a melting point of 50 to 80 ° C. and an emulsifier (Japanese Patent Publication No. 57-48050),
-Water-in-oil (W / O) emulsified fat / oil composition in which an aqueous solution of ascorbic acid and salts thereof is emulsified in fat / oil to which lipophilic sorbitan fatty acid ester, sucrose fatty acid ester, polyglycerin condensed ricinoleate, etc. are added. (Japanese Patent Publication No. 63-96727, JP-A-6-34)
3400).

[0006] However, in the former, the crystal surface of L-ascorbic acids is coated with a high melting point solid fat to obtain W / O.
A method for forming a dispersed solid / solid interface, wherein L-
Although the stability of ascorbic acids is excellent, the L-ascorbic acid crystals used are coarse crystals of several tens of μm or more, and have a granular form of about 0.2 to 2 mm covered with a high melting point solid fat. The range of application is limited, and application to liquid products in particular becomes extremely difficult.

In the latter, the internal aqueous phase is 0.2 to 5 μm.
m / W emulsified composition is obtained, and the range of application is widened, but the physical strength of the emulsified interface is weak because L-ascorbic acid is in an aqueous solution state, and decomposition occurs after a heating step such as sterilization. It has a disadvantage that the emulsified state is liable to undergo phase inversion destruction when exposed to physical stress such as stirring or pumping because of a W / O emulsified liquid / liquid interface.

[0008]

SUMMARY OF THE INVENTION The object of the present invention is to provide an L-
An object of the present invention is to provide a collagen synthesis promoter having a collagen synthesis promotion effect with extremely excellent stability by keeping ascorbic acid and its derivatives stable for a long period of time.

[0009]

Means for Solving the Problems The present inventors have made intensive studies in order to solve the above-mentioned problems, and as a result, have found that the synthesis of collagen containing L-ascorbic acids, nonionic surfactants and neutral lipids is promoted. It has been found that the agent has a collagen synthesis promoting effect with extremely excellent stability and that the skin cosmetic composition containing the collagen synthesis promoter of the present invention has an excellent wrinkle improving effect, and has completed the present invention. . That is, the present invention provides a method of dispersing L-ascorbic acids, which are ultrafine particles having an average particle size of 3 μm or less by physical crushing, into a nonionic surfactant having an HLB of 4 or less and a neutral lipid having a melting point of 45 ° C. or less in a neutral lipid. The present invention relates to a collagen synthesis promoter and a skin cosmetic containing the same. still,
The present inventors have confirmed the sustained release of L-ascorbic acids in the composition by the action of epidermal water by making the composition in which L-ascorbic acids are dispersed in the W / O.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The L-ascorbic acid and its derivatives in the present invention are not particularly limited as long as they have an effect of promoting collagen synthesis. It is preferable that the particles have properties that are insoluble in neutral lipids and can be converted into ultrafine particles having an average particle size of 3 μm or less by laser diffraction particle size distribution measurement by physical crushing. Specific examples of L-ascorbic acids are shown below, but are not limited thereto. L
Specific examples of -ascorbic acids include L-ascorbic acid, L-ascorbic acid-2-phosphate, L-ascorbic acid-3-phosphate, L-ascorbic acid diphosphate, L-ascorbic acid triphosphate, L-ascorbic acid-2-sulfate, L-ascorbic acid-3-sulfate, L-ascorbic-
2 sulfonates and their sodium, potassium, magnesium, calcium, aluminum, barium, ammonium, ethanolamine, diethanolamine, triethanolamine salts,
2-O-α-D-glucopyranosyl-L-ascorbic acid, 5-O-α-D-glucopyranosyl-L-ascorbic acid, such as monoisopropanolamine salt, diisopropanolamine salt, triisopropanolamine salt, and tricyclohexylammonium salt , 6-O-α-D-glucopyranosyl-L-ascorbic acid, 2-O-β-D
-Galactopyranosyl-L-ascorbic acid, 2,3-
L-ascorbic acid sugar derivatives such as di-O- (β-D-glucopyranosyl) -L-ascorbic acid, ascorbic acid phosphoramide derivatives, ascorbic acid-hydroxycarboxylic acid conjugates, and ascorbic acid-arbutin conjugates. Regarding the physical crushing method, use of a wet crusher such as a co-ball mill, a dry crusher such as a jet mill, or freeze crushing using liquid nitrogen, etc. is mentioned, but the average particle size is 3 μm or less by laser diffraction type particle size distribution measurement. Any material may be used as long as it is capable of forming ultrafine particles of preferably 1 μm or less, more preferably 0.5 μm or less. When the average particle size is larger than 3 μm, the dispersion stability in neutral lipids is reduced, and fine particles of L-ascorbic acids precipitate and separate.

The content of the L-ascorbic acids of the present invention is not particularly limited, but is preferably 1 to 70% by weight, more preferably 15 to 50% by weight in the composition. When the amount of L-ascorbic acids is less than 1% by weight, the amount of L-ascorbic acids, which is the main agent, becomes very small, so that it cannot be used as a collagen synthesis promoter.
On the other hand, when the amount of L-ascorbic acids is more than 70% by weight, the structural viscosity becomes extremely high and the fluidity is lost, so that the subsequent processing characteristics and application range are remarkably narrowed.

The nonionic surfactant used in the present invention is not particularly limited, but is preferably a glycerin fatty acid ester, a propylene glycol fatty acid ester, a sorbitan fatty acid ester, a glycerin alkyl ether, or a polyoxygen, which can be used as an external preparation for skin. Ethylene (hereinafter abbreviated as POE-) fatty acid ester, POE-glycerin fatty acid ester, POE-sorbitan fatty acid ester, POE-sorbit fatty acid ester, POE-
Alkyl ether, POE-glycerin alkyl ether, POE-alkylphenyl ether, POE-polyoxypropylene glycol, POE-polyoxypropylene alkyl ether, POE-castor oil, POE-
Hardened castor oil, polyethylene glycol fatty acid esters, and the like are preferable, and nonionic surfactants having an HLB of 4 or less are more preferable. Specific examples of the nonionic surfactant are shown below, but are not limited thereto. Specific examples of the nonionic surfactant include glycerin monofatty acid ester, glycerin difatty acid ester, organic acid monoglyceride, polyglycerin fatty acid ester, and polyglycerin condensed ricinoleate, preferably glycerin monostearate, glycerin monooleate, and glycerin monomillimilate. State, glycerin monocaprylate, glycerin distearate, glycerindiolate, glyceride citrate, glyceride malate, glyceride acetate, glyceride succinate, glyceride lactate, glyceride diacetyltartrate, glyceride acetylamino acid, glyceride pyroglutamate, average polymerization degree 2 And polyglycerol having 6 to 22 carbon atoms and an average degree of polymerization of 2 to 10
Glycerin fatty acid esters such as one or a mixture of two or more selected from polyglycerin and polyricinoleic acid esters having a degree of condensation of 2 to 4, and propylene glycol fatty acid esters such as propylene glycol monostearate and propylene glycol monooleate And sorbitan fatty acid esters such as sorbitan distearate, sorbitan tristearate, sorbitan sesquiolate, sorbitandiolate, and sorbitan triolate; and glycerin alkyl ethers such as monoisostearyl glyceryl ether and monomyristyl glyceryl ether. The nonionic surfactant is blended in an amount of 1 to 100% by weight based on the neutral lipid. However, if the addition amount is less than 1% by weight, it is impossible to sufficiently disperse the L-ascorbic acid fine particle crystals. If the amount is more than 10% by weight, when the composition is newly dispersed in an aqueous system, the contained L-ascorbic acid fine particles are liable to be eluted due to emulsification phase inversion, which hinders the formation of a stable W / O / W emulsion system. Come.

The neutral lipid used in the present invention is not particularly limited, but synthetic oils such as fatty acid esters, polyhydric alcohol fatty acid esters, medium-chain fatty acid triglycerides and hydrogenated products thereof, soybean oil, rice oil, rapeseed oil , Cottonseed oil,
Sesame oil, safflower oil, castor oil, olive oil, cacao oil, camellia oil, sunflower oil, palm oil, flax oil, perilla oil, shea oil, monkey oil, coconut oil, wood wax, jojoba oil, grape seed oil, avocado oil, Any of vegetable oils such as meadow home, mink oil, egg yolk oil, animal oils such as beef tallow, milk fat and lard can be used. In addition, hydrocarbons such as squalane, squalene, liquid paraffin, inparaffin, and silicone oil, and mineral oils may be included in the neutral lipid used in the present invention. Furthermore, phospholipids originally contained in these,
Although sterols, waxes, oil-soluble vitamins, and the like may coexist, oil components that can be used in a heating region having a melting point of 45 ° C. or lower are preferable, and more preferably have a melting point of room temperature or lower. If a neutral lipid having a melting point higher than 45 ° C. is used, a plurality of heating steps are required at the time of preparing a collagen synthesis promoter and adding it to cosmetics, etc., so that a strong heat history is given to L-ascorbic acids, The range will be narrowed.

The skin cosmetic of the present invention contains, in addition to the collagen synthesis promoter prepared as described above, surfactants, oils and fats, polyhydric alcohols, lower alcohols, thickeners and ultraviolet absorbers generally used in cosmetics. -Scattering agents, preservatives, antioxidants, chelating agents, pH adjusters, fragrances, pigments, water, etc. can be appropriately blended. Specific examples of these additional components are as follows. Examples of the surfactant include POE-branched alkyl ethers such as polyoxyethylene (hereinafter abbreviated as POE-) octyldodecyl alcohol, POE-2-decyltetradecyl alcohol, POE-oleyl alcohol ether, and POE such as POE-cetyl alcohol ether. Sorbitan esters such as alkyl ethers, sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, POE-sorbitan monooleate, POE-sorbitan monoisostearate, PE such as POE-sorbitan monolaurate;
Glycerin fatty acid esters such as OE-sorbitan ester, glycerin monooleate, glycerin monostearate, glycerin monomyristate, POE such as POE-glycerin monooleate, POE-glycerin monostearate, and POE such as POE-glycerin monomyristate
E-glycerin fatty acid ester, POE-dihydrocholesterol ester, POE-hardened castor oil, POE-
POE such as hardened castor oil isostearate; fatty acid ester of hardened castor oil; POE-alkyl aryl ether such as POE-octyl phenyl ether; glycerin alkyl ether such as monoisostearyl glyceryl ether and monomyristyl glyceryl ether; POE-monostearyl glyceryl Ethers, POE-glycerin alkyl ethers such as POE-monomilliglyceryl stil ether, diglyceryl monostearate, decaglyceryl decastearate, decaglyceryl decaisostearate, and polyglycerin fatty acid esters such as diglyceryl diisostearate. Nonionic surfactants, myristic acid, stearic acid, palmitic acid, behenic acid,
Potassium, sodium, diethanolamine, triethanolamine, salts of amino acids and the like of higher fatty acids such as isostearic acid and oleic acid, the above-mentioned alkali salts of ether carboxylic acids, salts of N-acyl amino acids, N-acyl sarconates, higher alkyl sulfonic acids Anionic surfactants such as salts; cationic surfactants such as alkylamine salts, polyamines, amino alcohol fatty acid organic silicone resins, and alkyl quaternary ammonium salts; and amphoteric surfactants such as lecithin and betaine derivatives.

The fats and oils include castor oil, olive oil,
Vegetable oils such as cacao oil, camellia oil, coconut oil, wood wax, jojoba oil, grape seed oil, avocado oil, animal oils such as mink oil, egg yolk oil, beeswax, whale wax, lanolin, carnauba wax, candelilla wax, etc. Waxes, liquid paraffin, squalene, microcrystalline wax, ceresin wax, paraffin wax, hydrocarbons such as petrolatum, lauric acid, myristic acid, stearic acid,
Oleic acid, isostearic acid, natural and synthetic fatty acids such as behenic acid, cetanol, stearyl alcohol,
Natural and higher alcohols such as hexyldecanol, octyldecanol, and lauryl alcohol; and esters such as isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, octyldodecyl oleate, and cholesterol oleate. Examples of polyhydric alcohols include polyglycerin such as ethylene glycol, polyethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, dipropylene glycol, glycerin, diglycerin, triglycerin, and tetraglycerin, glucose, and maltose. , Maltose, sucrose, fructose, xylitol, sorbitol, maltotriose, threitol, erythritol and the like. Examples of the thickener include sodium alginate, xanthan gum, aluminum silicate, quince seed extract, tragacanth gum, starch, collagen, natural polymer substances such as sodium hyaluronate, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, soluble starch, and cationized cellulose. Semi-synthetic polymer substances such as carboxyvinyl polymer and polyvinyl alcohol.

Examples of the ultraviolet absorber include paraaminobenzoic acid, isopropyl paramethoxycinnamate, butylmethoxybenzoylmethane, glyceryl-mono-2-ethylhexanoyl-di-paramethoxybenzophenone, digalloyltrioleate and 2-2 '. -Dihydroxy-4-methoxybenzophenone, ethyl-4-bishydroxypropylaminobenzoate, 2-ethylhexyl-2-cyano-3,3'-diphenylacrylate, ethylhexyl paramethoxycinnamate, 2-ethylhexyl salicylate, glyceryl paraaminobenzoate , Homomethyl salicylate, methyl orthoaminobenzoate, 2-hydroxy-4-methoxybenzophenone, amyl-para-
Dimethylaminobenzoate, 2-phenylbenzimidazole-5-sulfonic acid, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and the like. Preservatives include benzoate, salicylate, sorbate, dehydroacetate, p-hydroxybenzoate, 2,4,4
4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorocarbanilide, benzalkonium chloride, hinokitiol, resorcinol, ethanol and the like. Antioxidants include tocopherol, ascorbic acid, butylhydroxyanisole, dibutylhydroxytoluene, nordihydroguaiaretinic acid, propyl gallate and the like. As a chelating agent, sodium edetate, sodium citrate and the like. Some of these additional components have a function of further improving the effectiveness of the skin cosmetic of the present invention by increasing the stability or transdermal absorption of the essential components of the present invention.

Other substances that enhance the wrinkle-suppressing effect of the skin cosmetics of the present invention include other known collagen synthesis-promoting effects, collagenase activity-inhibiting effects, collagen cross-linking / insolubilization-suppressing effects, insoluble collagen degradation-promoting effects, hyaluronic acid, and the like. Mucopolysaccharide synthesis promoting action, hyaluronidase activity inhibitory action, hyaluronic acid and other mucopolysaccharide fragmentation inhibitory action,
Elastin synthesis promoting action, elastase activity inhibiting action,
And a substance having a Maillard reaction inhibitory action, a collagen metabolism activator, an L-ascorbic acid uptake promoter, a dermal fibroblast activator / proliferation promoter, and the like, directly or indirectly, such as collagen, hyaluronic acid, It is also possible to combine substances having an action of accelerating the renewal or turnover of elastin. That is, estradiol, testosterone, transforming growth factor (TGF) -β, vitamin A, which have a collagen synthesis promoting action,
Betulinic acid, Asian acid, Asiaticoside, α-hydroxy acid and its salt, Benzoamide compound, Sericin decomposition product, Egg shell membrane decomposition product, Placenta extract, Whey fraction, Reishi extract, Rice protein decomposition product , Rice bran hydrolyzate, tochu leaf extract, and other known substances having a collagen synthesis promoting action, rosmarinic acid having a collagen cross-linking inhibitory action, Labiatae extract, juniper extract, vitamin B ₆ and its derivatives, and Other known substances having a collagen cross-linking / insolubilization inhibitory action, silk hydrolyzates and their ester derivatives having an insoluble collagen decomposition accelerating action, and other known collagen degrading accelerating action, collagenase inhibitory activity Various plant extracts such as collagenase inhibitors, animal cartilage extracts, Artemisia plant extracts having And other known substances having an inhibitory effect on collagenase activity, isoflavonoid compounds called phytoestrogens, such as genistein, daidzein, and miloestol, which have a mucopolysaccharide synthesis promoting action such as hyaluronic acid, lavender extract, yeast extract, insulin-like Growth factor-1, epidermal growth factor, interleukin-1, phorbol ester, and other known substances having a mucopolysaccharide synthesis promoting action such as hyaluronic acid, chondroitin sulfate and its salts having a hyaluronidase activity inhibitory action, and cardanol derivatives , And other known substances having an inhibitory action on hyaluronidase activity, vitamin E, glutathione, glutathione peroxidase, superoxide dismutase having an inhibitory action on fragmentation or degradation of mucopolysaccharides such as hyaluronic acid , Quercetin derivative, uric acid, transferrin, ceruloplasmin, astaxanthin, caffeine, gokahi, dokudami, clove, etc., and crude drug extracts such as hyaluronic acid and other substances having mucopolysaccharide fragmentation inhibitory or decomposition inhibitory activity, elastin Erythorbic acid and its derivatives having a synthesis promoting action, green tea extract, and other substances having a known elastin synthesis promoting action; adenyl derivatives such as adenosine triphosphate and adenosine monophosphate having a dermal fibroblast activating action; Salts thereof, α-hydroxy acids such as glycolic acid, lactic acid, and salicylic acid and derivatives thereof, nucleic acid-related substances such as ribonucleic acid, epidermal growth factor, fibroblast growth factor, and other known dermal fibroblast activation It is possible to combine substances with action Thus, a synergistic effect of suppressing wrinkle formation and reducing wrinkles can be provided. Further, the dosage form of the skin cosmetic of the present invention is also arbitrary, and may be any of a soluble type, an emulsifying type, a powdered dispersing type, etc., and is used for basic cosmetics such as lotions, emulsions, creams, packs, etc., as well as foundations. It can be used widely for makeup cosmetics, eyeliners, bath cosmetics, etc.

Hereinafter, the collagen synthesis promoter and skin cosmetic of the present invention will be described with reference to Examples and Test Examples, but the present invention is not limited thereto.

[0019]

EXAMPLES Example 1 Constituent fatty acids having 8 and 10 carbon atoms (C ₈ : C ₁₀ = 3:
1) 50 parts by weight of medium-chain fatty acid triglyceride (melting point −11 ° C., manufactured by Taiyo Chemical Co., Ltd.), 10 parts by weight of polyglycerin condensed ricinoleate (Sunsoft 818)
H; HLB1, manufactured by Taiyo Kagaku Co., Ltd.), and 40 parts by weight of L-ascorbic acid crystals (average particle size of about 100 μm)
m, manufactured by Nippon Roche Co., Ltd.) to prepare an oily suspension, which is then subjected to Koball Mill (manufactured by Shinko Pantech Co., Ltd.)
To obtain a collagen synthesis accelerator as a W / O dispersion composition in which the average particle size of L-ascorbic acid was 0.4 μm by laser diffraction particle size distribution measurement.

Example 2 Rapeseed white squeezed oil 70 parts by weight (melting point 12 ° C.), polyglycerin condensed ricinoleate 5 parts by weight (Sunsoft 81)
8H; HLB1, manufactured by Taiyo Chemical Co., Ltd.) and 5 parts by weight of polyglycerin stearate (Sun Fat PS)
-68; HLB3.5, manufactured by Taiyo Chemical Co., Ltd.), and added with 20 parts by weight of magnesium L-ascorbic acid monophosphate crystal (average particle size: about 100 μm, manufactured by Takeda Pharmaceutical Co., Ltd.). And subjected to a Koball Mill (manufactured by Shinko Pantech Co., Ltd.), and the average particle diameter of the magnesium L-ascorbic acid monophosphate crystal was determined to be 0.35 μm by a laser diffraction type particle size distribution measurement. A collagen synthesis promoter was obtained.

Example 3 Constituent fatty acids having 8 and 10 carbon atoms (C ₈ : C ₁₀ = 3:
1) 50 parts by weight of a medium-chain fatty acid triglyceride (melting point −11 ° C., manufactured by Taiyo Kagaku Co., Ltd.), 5 parts by weight of polyglycerin condensed ricinoleate (Sunsoft 818S)
X; HLB 0.5, manufactured by Taiyo Kagaku Co., Ltd.), 5 parts by weight of citric acid monoglyceride (Sunsoft 623M; HLB)
4, manufactured by Taiyo Kagaku Co., Ltd.) to prepare an oily suspension to which 40 parts by weight of L-ascorbic acid crystals (average particle size: about 100 μm, manufactured by Nippon Roche Co., Ltd.) was added. (Manufactured by Tech Co., Ltd.) to obtain a collagen synthesis accelerator as a W / O dispersion composition having an average particle size of L-ascorbic acid of 0.4 μm as measured by laser diffraction particle size distribution measurement.

Test Example 1 Stability test of L-ascorbic acid Constituent fatty acids having 8 and 10 carbon atoms (C ₈ : C ₁₀ = 3:
1) 50 parts by weight of medium-chain fatty acid triglyceride (melting point −11 ° C., manufactured by Taiyo Chemical Co., Ltd.), 10 parts by weight of polyglycerin condensed ricinoleate (Sunsoft 818)
H; HLB1, manufactured by Taiyo Chemical Co., Ltd.)
While adding 40 parts by weight (pH 2.0) of an aqueous solution of L-ascorbic acid, high-speed stirring was performed with a homomixer (manufactured by Tokushu Kika Kogyo Co., Ltd.), and the average particle size of the internal aqueous phase was determined to be 0 by laser diffraction type particle size distribution measurement. A W / O emulsion having a thickness of 0.4 μm was prepared. Using this as a control, the oxidative stability of L-ascorbic acid in the collagen synthesis promoter, which is the W / O dispersion composition of Example 1, was compared.

200 g of each of the two was sealed in a pressure bottle and sterilized by heating at 121 ° C. for 30 minutes.
g, 200 ml of a 2% aqueous solution of metaphosphoric acid and 200 ml of n-hexane were added, and the mixture was shaken and extracted at room temperature.
The obtained aqueous layer was collected and filtered through a 0.45 μm membrane filter to obtain a test solution, and H was provided with an amide-bonded reversed-phase column (Amid 80, manufactured by Tosoh Corporation).
The amount of L-ascorbic acid was measured by PLC. The elution solvent used was an acetonitrile / 2.5 mM potassium phosphate solution (50/50), and the detection was measured by the absorbance at 254 nm. Then, both are stored at 50 ° C. for 3 months,
The same measurement as described above was performed every month, and the emulsified state was observed.

In the presence of water, L-ascorbic acid easily loses a hydrogen atom from the enol groups at the 2- and 3-positions to give a keto-isomer, dehydroascorbic acid, and when oxidation proceeds further, 2,3-diketogulonic acid To decompose into oxalic acid. Only L-ascorbic acid in these compounds is 25%
Because it has the property of exhibiting specific absorption at a wavelength of 4 nm,
Using this as an index, the residual ratio of L-ascorbic acid was determined, and the stability as L-ascorbic acid was compared.

As a result, as shown in Table 1, in the collagen synthesis promoter of Example 1, the attenuation of L-ascorbic acid hardly occurred, and excellent stability was exhibited.

[0026]

[Table 1]

Test Example 2 Stability test of L-ascorbic acid (at the time of W / O / W emulsification) Constituent fatty acids having 8 and 10 carbon atoms (C ₈ : C ₁₀ = 3:
1) 50 parts by weight of medium-chain fatty acid triglyceride (melting point −11 ° C., manufactured by Taiyo Chemical Co., Ltd.), 10 parts by weight of polyglycerin condensed ricinoleate (Sunsoft 818)
H; HLB1, manufactured by Taiyo Chemical Co., Ltd.)
While adding 40 parts by weight (pH 2.0) of an L-ascorbic acid aqueous solution, high-speed stirring was performed with a homomixer (manufactured by Tokushu Kika Kogyo Co., Ltd.), and the average particle size of the internal aqueous phase was determined to be 0 by laser diffraction type particle size distribution measurement. A W / O emulsion having a thickness of 0.4 μm was prepared. This was added to 1000 parts by weight of water in which 5 parts by weight of sucrose fatty acid ester (Ryoto Sugar Ester S-1670, manufactured by Mitsubishi Chemical Corporation) was dissolved and stirred to prepare a W / O / W emulsion.

Similarly, the W / O dispersion composition of Example 3 was added to 1000 parts by weight of water in which 5 parts by weight of sucrose fatty acid ester (Ryoto Sugar Ester S-1670, manufactured by Mitsubishi Chemical Corporation) was dissolved. Stir to prepare a W / O / W emulsion, seal 200 g of each with a pressure bottle,
The solution was sterilized by heating at 21 ° C. for 15 minutes. After cooling, 50 g of the solution was collected, 200 ml of a 2% aqueous solution of metaphosphoric acid and 200 ml of n-hexane were added, and the mixture was shaken and extracted at room temperature. Was collected and filtered through a 0.45 μm membrane filter to obtain a test solution, and an HPL equipped with an amide-bonded reverse-phase column (Amide 80, manufactured by Tosoh Corporation) was used.
C was used to measure the amount of L-ascorbic acid. The elution solvent was acetonitrile / 2.5 mM potassium phosphate solution (50 mM).
/ 50), and the detection was measured by the absorbance at 254 nm. Thereafter, both were stored at 40 ° C. for 3 weeks, and the same measurement was carried out every week, and the emulsified state was observed.

As a result, as shown in Table 2, W of Example 3
The collagen synthesis promoter, which is a / O dispersion composition, is a W / O
Even under unstable emulsifying conditions of the / W type, L-ascorbic acid hardly attenuated, showing excellent stabilization.

[0030]

[Table 2]

Test Example 3 Stability test of L-ascorbic acid (addition to lotion) 3 parts by weight of the collagen synthesis promoter of Example 3 was added to 100 parts by weight of a commercially available lotion, and mixed by stirring.
g of L-ascorbic acid-containing lotion was prepared. As a control, 1.2 parts by weight of L-ascorbic acid was applied to the same lotion 1
A lotion added and dissolved in 00 parts by weight was prepared, and the residual ratio of L-ascorbic acid in both was compared.

When the residual ratio of L-ascorbic acid was analyzed according to the measuring method of Test Example 2, the residual ratio was 28.7% for the control product, whereas the collagen synthesis promoter of Example 3 was used. The residual ratio in the one added was 94.5%,
The effect of the present invention in water-based cosmetics was sufficiently confirmed.

Test Example 4 Collagen synthesis promoting ability test of cultured fibroblasts (SB Russel (Biochem)
Istry, 10, 988, 1971) and B.I. Pet
erkofsky (J. Cell. Physiol.,
97, 221, 1978) et al.) Hexane was added to 1 g of the collagen synthesis promoter of Example 1, and the precipitate obtained by centrifugation was further washed repeatedly with hexane. Vacuum drying was performed in a refrigerator in a dark place to completely remove hexane. After dissolving the obtained dried product in 200 ml of water, the solution was sterilized by filtration to obtain Sample A of the present test. The same operation was performed on the collagen synthesis promoter of Example 1 that had been stored at 40 ° C. for 6 months to obtain a sample B. Next, the subcultured WI
An aqueous solution of the above sample was added to -38 cells (human fetal lung normal diploid cells) under a low serum culture condition of MEM medium (containing 0.5% fetal bovine serum), and then added to 5% CO ₂ + 95% Air. At 37 ° C. for 4 days, and 50 μl of ³ H-proline (200 μCi / ml) was added to 5 ml of the medium to give 5% C
The cells were cultured at 37 ° C. for 6 hours in O ₂ + 95% Air. In addition, the sample-free group was used as a control. Thereafter, the culture supernatant was removed, and collagenase type I (Worthi) was added to the cell fraction.
5 units / ml (manufactured by ngton) at 37 ° C. for 18 hours, deproteinized with a trichloroacetic acid solution, and the soluble fraction was mixed with Hionic flow to measure the radiation dose. In the evaluation of the ability to promote collagen synthesis, neutral lipids and nonionic surfactants were removed with a solvent, and the solvent was removed by drying under reduced pressure at low temperature, considering that the sample was directly added to cultured cells. However, this does not limit the collagen synthesis promoter of the present invention.

The amount of the sample to be added to the medium is described below. Addition amount (V / V culture solution%) Sample A: 0.5% Sample B: 0.5%

The results are shown in Table 3. The collagen synthesis promoting activity was not lost under the conditions of abuse at 40 ° C. for 6 months after the preparation of the collagen synthesis promoter. This result is apparently due to the fact that the storage stability of L-ascorbic acids contained in the collagen synthesis promoter of the present invention is extremely good over a long period of time.

[0036]

[Table 3]

Test Example 5 Patch Test A closed patch test was performed on the upper arm flexion side of a subject consisting of a total of 30 males and 14 females aged 21 to 55 years. The collagen synthesis promoters of Examples 1 to 3 were used as samples.

Criteria for judgment-: no reaction, ±: slight erythema, +: clear erythema, ++: erythema and swelling, papule

As a result, for each sample, all subjects
-(No reaction at all), very unlikely to cause irritative or allergic reactions, clearly indicating that the collagen synthesis promoter of the present invention is highly safe and can be incorporated into skin cosmetics. It became.

Test Example 6 Panel test 1 30-45 years old with wrinkle worries (average age 40.2
Of 50), the half of which is 25, the latex of Example 6 which is the skin cosmetic of the present invention described later, and the other half is the collagen synthesis promoter of Example 5 from Example 5. Table 4 shows the sensory evaluation as a result of applying a cream (control skin cosmetic) twice a day (morning and evening) to the face for three consecutive months without using the same.

[0041]

[Table 4]

As is clear from Table 4, the skin cosmetic of the present invention of Example 6 showed high effectiveness in wrinkles, textures and moist feelings. It is clear that this effect is due to the collagen synthesis promoter of the present invention contained in the skin cosmetic of the present invention.

Test Example 7 Panel Test 2 A panel test was conducted on 50 long-term preserved skin cosmetics of the present invention for 50 women aged 28 to 45 who had wrinkles. Twenty-five of the 50 females applied the skin cosmetic of the present invention described later to the other half, and the other half applied the control skin cosmetic to the face twice a day (morning and evening) for three consecutive months.
The cream of Example 5 was prepared in the skin cosmetic of the present invention,
The control skin cosmetics contained the same concentration of L-ascorbic acid as the cream of Example 5 except that the collagen synthesis promoter of Example 1 was used instead of Example 5 and the formulation using a 40% aqueous solution of L-ascorbic acid was used instead. Prepare a cream to be
After the preparation of each cosmetic, those stored at 40 ° C. for 6 months were used. Table 5 shows the results of the sensory evaluation.

[0044]

[Table 5]

As is evident from Table 5, it was confirmed that the skin cosmetic of the present invention to which the collagen synthesis promoter of the present invention was added prevented skin wrinkles and gave a fine and moist skin. It is clear that this effect is due to the collagen synthesis promoter of the present invention contained in the skin cosmetic of the present invention. Even after the preparation of the skin cosmetic, the storage stability of L-ascorbic acids encapsulated for a long period of time is improved. It was confirmed to be extremely good.

Example 4 <Lotion> Glycerin 5 parts Propylene glycol 4 parts Oleyl alcohol 0.1 parts Polyoxyethylene sorbitan monolaurate 1.5 parts Polyoxyethylene lauryl ether 0.5 parts Ethanol 10 parts Collagen synthesis promoter 10 parts Perfume, dye, preservative, UV absorber qs Purified water 68.9 parts

Example 5 <Cream> Stearyl alcohol 7 parts Stearic acid 2 parts Reduced lanolin 5 parts Squalane 6 parts Octidedecanol 3 parts Polyoxyethylene cetyl ether 2 parts Lipophilic glyceryl monostearate 5 parts Propylene glycol 5 parts Collagen synthesis promoter of Example 1 10 parts Perfume, preservative, antioxidant Appropriate amount Purified water 55 parts

Example 6 <Emulsion> Stearic acid 0.2 parts Cetanol 1.5 parts Vaseline 3 parts Lanolin alcohol 2 parts Liquid paraffin 10 parts Polyoxyethylene monooleate 2 parts Glycerin 3 parts Propylene glycol 5 parts Triethanolamine 1 part Collagen synthesis promoter of Example 2 15 parts Perfume, preservative, antioxidant qs Purified water 57.3 parts

Example 7 <pack> 15 parts of polyvinyl alcohol 5 parts of sodium carboxymethylcellulose 5 parts of propylene glycol 3 parts of ethanol 5 parts of the collagen synthesis promoter of Example 3 5 parts Perfume, preservative, oxidizing agent Appropriate amount of purified water 62 parts

[0050]

Industrial Applicability The collagen synthesis promoter of the present invention has various L-ascorbic acids which are unstable as they are, which are extremely stabilized. Even when dispersed in an aqueous cosmetic such as a lotion, L- encapsulated by emulsification phase inversion
Stable W / O / W without elution of ascorbic acids
It is characterized by constituting an emulsification system. In addition, when applied to the skin, it exerts a stable collagen synthesis promoting effect, and has high safety, so that clinical application is expected. Furthermore, in the skin cosmetics characterized by containing these collagen synthesis promoters, L-ascorbic acids stabilized by the collagen synthesis promoters maintain the collagen synthesis promotion effect derived from their physiological functions for a long time. It is to let. Therefore, the present invention makes it possible to easily supply an extremely stable collagen synthesis promoter, which has not been heretofore known, and has a great industrial significance.

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (reference) A61P 17/00 A61K 31/00 617 43/00 643D A61K 31/375 31/375 F term (reference) 4C083 AC012 AC022 AC022 AC072 AC092 AC102 AC122 AC182 AC352 AC402 AC422 AC442 AC542 AC902 AD112 AD272 AD512 AD641 AD642 BB04 BB11 CC04 CC05 CC07 DD31 EE01 EE12 EE50 4C086 AA01 AA02 BA18 MA17 MA22 MA28 MA63 NA14 ZA89 ZB21

Claims (5)

[Claims] 1. A collagen synthesis promoter comprising at least one selected from the group consisting of L-ascorbic acid and its derivatives, a nonionic surfactant and a neutral lipid. 2. The collagen synthesis promoter according to claim 1, wherein at least one selected from the group consisting of L-ascorbic acid and a derivative thereof is a solid having an average particle size of 3 μm or less. 3. The collagen synthesis promoter according to claim 1, wherein the nonionic surfactant is HLB4 or less. 4. The collagen synthesis promoter according to claim 1, wherein the neutral lipid has a melting point of 45 ° C. or lower. 5. A skin cosmetic comprising the collagen synthesis promoter according to any one of claims 1 to 4.