JP2000086442A - Skin whitening preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare the subject preparation capable of stably retaining L- ascorbic acids for a long period, having skin whitening effect excellent in stability and useful for skin cosmetics such as skin lotion, milky lotion or the like by including L-ascorbic acid, a nonionic surfactant or the like. SOLUTION: This skin whitening preparation for external use is prepared by including (A) L-ascorbic acid and/or its derivative (pref. solid having <=1 μm average particle diameter) (e.g. L-ascorbic acid crystals or the like) pref. in a content of 15-50 wt.% based on the weight of the above preparation), (B) a nonionic surfactant (pref. showing <=HLB4)(e.g. polyglycerin-condensed ricinoleate) pref. in a content of 1-100 wt.% based on the weight of the component C and (C) a neutral lipid pref. having <=45 deg.C melting point (e.g. a medium chain fatty acid triglyceride or the like). The preparation is useful for cream, pack, foundation or the like.

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.
Skin whitening agent for external use containing a seed (hereinafter referred to as L-ascorbic acid) as a physiologically active ingredient, and a skin cosmetic containing the same (including quasi-drugs and medicinal cosmetics; the same applies hereinafter). It is about.

[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, L-ascorbic acid and its derivatives prepared as described above have insufficient storage stability or cannot withstand heat sterilization, and therefore cannot exert a sufficient effect when applied to skin, and have a whitening effect. In many cases, the effect and the effect of preventing inflammation due to ultraviolet rays were not sufficiently recognized. 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 skin whitening external preparation having extremely excellent stability and a whitening effect by keeping ascorbic acid and its derivatives stable for a long period of time.

[0009]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that whitening skin containing L-ascorbic acids, a nonionic surfactant and a neutral lipid. The present inventors have found that an external preparation has an extremely stable whitening effect, and have completed the present invention.

That is, according to the present invention, ultrafine L-ascorbic acids having an average particle size of 1 μm or less by physical crushing are prepared from a nonionic surfactant having an HLB of 4 or less and a melting point of 45 ° C.
The present invention relates to a skin cosmetic comprising a whitening skin external preparation and W / O dispersed in a neutral lipid. In addition, the present inventors converted the L-ascorbic acids into the W
By making the composition dispersed in / O, it has been confirmed that a sustained release effect of L-ascorbic acids due to the sensitivity between the composition and the skin surface moisture.

BEST MODE FOR CARRYING OUT THE INVENTION

[0011] The L-ascorbic acid and its derivatives in the present invention are not particularly limited as long as they have a whitening effect, but are preferably known whitening agents conventionally used. It is preferable that the material is insoluble and can be converted into ultrafine particles having an average particle size of 1 μm or less by laser diffraction type particle size distribution measurement by physical crushing. Specific examples of L-ascorbic acids are shown below, but are not limited thereto. Specific examples of L-ascorbic acids include L-ascorbic acid, L-ascorbic acid monophosphate, L-ascorbic acid diphosphate, L-ascorbic acid triphosphate, L-ascorbic acid-2-sulfate, and L-ascorbic acid-2-sulfate. Ascorbic acid-2-sulfonic acid esters and their sodium salts,
Potassium salt, magnesium salt, calcium salt, aluminum salt, barium salt, ammonium salt, ethanolamine salt, diethanolamine salt, triethanolamine salt, monoisopropanolamine salt, diisopropanolamine salt, triisopropanolamine salt, tricyclohexylammonium salt, etc. , 2-O-α-D-glucopyranosyl-L-ascorbic acid, 5-O-α-D-glucopyranosyl-L-ascorbic acid, 6-O-α-D
-Glucopyranosyl-L-ascorbic acid, 2-O-β
-D-galactopyranosyl-L-ascorbic acid, 2,
L-ascorbic acid sugar derivatives such as 3-di-O- (β-D-glucopyranosyl) -L-ascorbic acid, ascorbic acid phosphoramide derivatives, ascorbic acid-hydroxycarboxylic acid conjugates, ascorbic acid-arbutin conjugates, and the like. Can be Regarding the physical crushing method, use of a wet crusher such as a Koball mill or a Dyno-mill or a dry crusher such as a jet mill, or freeze crushing using liquid nitrogen, etc. Any material may be used as long as it has a performance capable of forming ultrafine particles having a particle size of 1 μm or less. If the average particle size is larger than 1 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 ingredient, becomes very small, so that it cannot be used as an external preparation for whitening skin. 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-alkyl ether, POE-glycerin alkyl ether, POE-alkylphenyl ether, POE-polyoxypropylene glycol, polyethylene glycol fatty acid Ester and the like are preferable, and a nonionic surfactant having an HLB of 4 or less is 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,
Glycerin monostearate, glycerin monooleate, glycerin monomyristate, glycerin monocaprylate, glycerin distearate, glycerindiolate, glyceride citrate, glyceride malate, glyceride acetate, glyceride succinate, glyceride lactate, diacetyltartaric acid Glyceride, acetylamino acid glyceride, pyroglutamic acid glyceride, polyglycerin having an average degree of polymerization of 2 to 10, fatty acid ester having 6 to 22 carbon atoms, and ester of polyglycinol having an average degree of polymerization of 2 to 10 and polyricinoleic acid having a degree of condensation of 2 to 4 Glycerin fatty acid esters such as one or a mixture of two or more selected from propylene glycol fatty acid esters such as propylene glycol monostearate and propylene glycol monooleate. Sorbitan 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. . Nonionic surfactant is 1 to 100% by weight based on neutral lipid
When the amount is less than 1% by weight, it is impossible to sufficiently disperse the L-ascorbic acid fine particle crystals. When the amount is more than 100% by weight, the composition is redispersed in an aqueous system. L-ascorbic acid particles contained therein are easily eluted due to emulsification phase inversion, and stable W /
This will hinder the construction of the O / W emulsification system.

The neutral lipid used in the present invention is not particularly limited, but synthetic fats and oils such as medium chain fatty acid triglyceride, soybean oil, rice oil, rapeseed oil, cottonseed oil, sesame oil, safflower oil, castor oil, olive oil, cacao oil Vegetable oils such as 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, mink oil, egg yolk oil, tallow oil And animal fats and oils such as milk fat and lard. In addition, hydrocarbons such as liquid paraffin, squalane, and squalene, and silicone oil may be included in the neutral lipid used in the present invention. Furthermore, although the phospholipids, sterols, waxes, oil-soluble vitamins, and the like originally contained therein may be coexistent, oil components that can be used in a heating region having a melting point of 45 ° C. or less are preferable, More preferably, the melting point is below room temperature. When a neutral lipid having a melting point higher than 45 ° C. is used, a plurality of heating steps are required at the time of preparation of an external preparation for whitening and addition to cosmetics, etc., so that a strong heat history is given to L-ascorbic acids, The range will be narrowed.

The skin cosmetics of the present invention include, in addition to the skin whitening preparations prepared as described above, surfactants, oils and fats, polyhydric alcohols, lower alcohols, thickeners, ultraviolet absorbers, which are generally used in cosmetics. Agents / scatterers, preservatives, antioxidants, chelating agents, pH adjusters, fragrances, dyes, water, etc. can be appropriately compounded. 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 ether, sorbitan monooleate, sorbitan monoisostearate and sorbitan monolaurate; POE such as POE-sorbitan monooleate, POE-sorbitan monoisostearate and POE-sorbitan monolaurate.
E-sorbitan ester, glycerin monooleate,
Glycerin fatty acid esters such as glycerin monostearate and glycerin monomyristate, POEs such as POE-glycerin monooleate, POE-glycerin monostearate and POE-glycerin monomyristate.
POE-hardened castor oil fatty acid esters such as glycerin fatty acid ester, POE-dihydrocholesterol ester, POE-hardened castor oil, POE-hardened castor oil isostearate, POE-alkyl aryl ether such as POE-octylphenyl ether, monoisostearyl Glycerin alkyl ethers such as glyceryl ether and monomyristyl glyceryl ether, POE-glycerin alkyl ethers such as POE-monostearyl glyceryl ether, POE-monomyristyl glyceryl ether, diglyceryl monostearate, decaglyceryl decasterate, decaglyceryl decaisoate Nonionic surfactants such as stearates, polyglycerin fatty acid esters such as diglyceryl diisostearate, myristic acid, stearin , Palmitic acid, behenic acid, isostearic acid, potassium higher fatty acids such as oleic acid,
Salts of sodium, diethanolamine, triethanolamine, amino acids, etc., the above alkali salts of ether carboxylic acids, salts of N-acyl amino acids, anionic surfactants such as N-acyl sarconates, higher alkyl sulfonates, and alkylamine salts And cationic surfactants such as 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. Further, placenta extract, cysteine, glucosamine, glutathione, hydroquinone, arbutin, kojic acid, glabridine, azelaic acid, other known whitening agents such as α-hydroxy acids and derivatives thereof, may also be combined with tyrosinase activity inhibitor and the like. It is possible to provide a whitening synergistic effect. 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 skin whitening agent and the skin cosmetic composition of the present invention will be described with reference to Examples and Test Examples, but the present invention is not limited thereto.

[0019]

Example 1 <External preparation for whitening skin> Constituent fatty acid has 8 or 10 carbon atoms.
50 parts by weight of a medium-chain fatty acid triglyceride (C ₈ : C ₁₀ = 3: 1) (melting point −11 ° C., manufactured by Taiyo Chemical Co., Ltd.);
10 parts by weight of polyglycerin condensed ricinoleate (Sunsoft 818H; HLB1, manufactured by Taiyo Chemical Co., Ltd.) were mixed, and 40 parts by weight of L-ascorbic acid crystals (average particle diameter: about 100 μm, manufactured by Nippon Roche Co., Ltd.) were added. An oily suspension was prepared, applied to a Koball Mill (manufactured by Shinko Pantec Co., Ltd.), and the average particle diameter of L-ascorbic acid was 0.4 μm by laser diffraction type particle size distribution measurement.
A W / O dispersion composition as described above was obtained.

Example 2 <External preparation for skin whitening> 70 parts by weight of rapeseed white oil (melting point: 12
C), 5 parts by weight of polyglycerin condensed ricinoleate (Sunsoft 818H; HLB1, manufactured by Taiyo Chemical Co., Ltd.) and 5 parts by weight of polyglycerin stearate (San Fat PS-68; HLB3.5, manufactured by Taiyo Chemical Co., Ltd.) ) Were mixed and 20 parts by weight of magnesium L-ascorbic acid monophosphate crystal (average particle size of about 100 μm)
m, manufactured by Takeda Pharmaceutical Co., Ltd.), applied to a Koball Mill (manufactured by Shinko Pantech Co., Ltd.), and subjected to laser diffraction type particle size distribution measurement to obtain L-ascorbic acid monophosphate magnesium salt crystal. Was obtained as a W / O dispersion composition having an average particle diameter of 0.35 μm.

Example 3 <External preparation for whitening skin> Constituent fatty acid has 8 or 10 carbon atoms.
50 parts by weight of a medium-chain fatty acid triglyceride (C ₈ : C ₁₀ = 3: 1) (melting point −11 ° C., manufactured by Taiyo Chemical Co., Ltd.);
5 parts by weight of polyglycerin condensed ricinoleate (Sunsoft 818SX; HLB0.5, manufactured by Taiyo Kagaku Co., Ltd.) and 5 parts by weight of citrate monoglyceride (Sunsoft 623M; HLB4, manufactured by Taiyo Kagaku Co., Ltd.) were mixed. An oily suspension containing 40 parts by weight of ascorbic acid crystals (average particle diameter of about 100 μm, manufactured by Nippon Roche Co., Ltd.) was prepared, and the suspension was applied to a Dyno-mill (manufactured by Shinmaruenterprisesu Co., Ltd.), and subjected to laser diffraction particle size analysis. According to distribution measurement, the average particle size of L-ascorbic acid was 0.4 μm.
Thus, an external preparation for skin whitening was obtained, which was a W / O dispersion composition of m.

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 oxidation state of L-ascorbic acid in the skin whitening external preparation, 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 reverse-phase column (Amide 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, L-ascorbic acid was hardly attenuated in the skin whitening preparation of Example 1, showing excellent stabilization.

[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 reversed-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 skin whitening agent for skin whitening which is a / O dispersion composition is W / O / W
Under the unstable emulsifying conditions of the mold, L-ascorbic acid hardly attenuated, indicating excellent stabilization.

[0030]

[Table 2]

Test Example 3 Stability test of L-ascorbic acid (addition to lotion) 3 parts by weight of the skin whitening agent for external use of Example 3 was added to a commercially available lotion 1
The mixture was added to 00 parts by weight and stirred and mixed to prepare a 1200 mg / g L-ascorbic acid-enriched lotion. As a control, 1.2 parts by weight of L-ascorbic acid was added to a similar lotion 100
A lotion added and dissolved in 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 in accordance with the measuring method of Test Example 2, the residual ratio of the control product was 28.7%, whereas the skin external preparation for whitening of Example 3 was found. Was 94.5%, and the effect of the present invention in aqueous cosmetics could be sufficiently confirmed.

Test Example 4 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 whitening skin external preparations 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 irritation and allergic reactions, high safety of the external preparation for whitening skin of the present invention, which can be incorporated into skin cosmetics. It became clear.

Test Example 5 Test for therapeutic effect on melasma For 40 women aged 19 to 43 who are suffering from melasma, half of the 20 skin creams of the present invention described in Example 5
And the other half of the cream (control skin cosmetic), excluding the whitening skin external preparation of Example 1 from Example 5, was applied twice daily (morning and evening) to the face for three consecutive months. After application, the lightening effect after use was determined.

Criteria for judgment Effective: Pigmentation was considerably reduced, somewhat effective: Pigmentation was slightly reduced, invalid:
There was no change in pigmentation.

The results are shown in Table 3. The skin cosmetic of the present invention of Example 5 showed a significant lightening effect. It is clear that this effect is due to the skin whitening agent of the present invention contained in the skin cosmetic of the present invention.

[0039]

[Table 3]

Test Example 6 Sunlight exposure test A sunshine exposure test was performed on 40 women aged 19 to 34 years. After exposing the inner skin of the upper arm of 40 women for 4 hours (2 hours a day for 2 days) in summer sunlight, the skin cosmetic of the present invention is applied to the inner skin of the left upper arm, and to the inner skin of the upper right arm. Applied the control skin cosmetics twice a day (morning and evening) for 4 consecutive weeks. The emulsion of Example 6 was prepared in the skin cosmetic of the present invention, and the skin whitening skin preparation of Example 2 was replaced with the skin cosmetic of Example 2 from Example 6 in the control skin cosmetic, and 20% magnesium L-ascorbate monophosphate was used instead. An emulsion containing the same concentration of magnesium L-ascorbate monophosphate as that of the emulsion of Example 6 was prepared by a formulation using an aqueous solution, and after each cosmetic was prepared, it was stored at 40 ° C. for 6 months. used. In addition, the evaluation compared the skin cosmetic application part skin of the present invention with the control skin cosmetic application part skin, and determined whether the skin cosmetic preparation of the present invention was superior to the control skin cosmetic based on the following criteria. .

Evaluation Criteria Effective: The skin cosmetic of the present invention had a stronger effect of preventing blackening as compared with the control skin cosmetic, and had the same skin color before the start of the test in the area where the skin cosmetic of the present invention was applied. Or a whitening effect was observed. Slightly effective: The skin cosmetic of the present invention was confirmed to have a more effective darkening prevention effect than the control skin cosmetic. Ineffective: In the skin cosmetic application part of the present invention, the same color black skin as the control skin cosmetic application part was confirmed. In addition, in this test, the skin of the control skin cosmetic applied part turned black in all subjects.

[0042]

[Table 4]

As apparent from Table 4, the effect of the skin cosmetic of the present invention to which the skin whitening agent of the present invention was added was more effective in preventing the deposition of an excess of melanin pigment after exposure to sunlight.
Prevention of darkening was recognized. It is clear that this effect is due to the skin whitening skin preparation of the present invention contained in the skin cosmetic of the present invention, and the storage stability of L-ascorbic acids encapsulated for a long time after preparation of the skin cosmetic. Was confirmed to be extremely good.

Example 4 <Lotion> Glycerin 5% Propylene glycol 4% Oleyl alcohol 0.1% Polyoxyethylene sorbitan monolaurate 1.5% Polyoxyethylene lauryl ether 0.5% Ethanol 10% Skin whitening topical preparation 10% Perfume, dye, preservative, UV absorber Appropriate amount Purified water 68.9%

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

Example 6 <Emulsion> Stearic acid 0.2% Cetanol 1.5% Vaseline 3% Lanolin alcohol 2% Liquid paraffin 10% Polyoxyethylene monooleate 2% Glycerin 3% Propylene glycol 5% Triethanolamine 1% Skin whitening external preparation of Example 2 15% Perfume, preservative, antioxidant Appropriate amount Purified water 57.3%

Example 7 <Pack> Polyvinyl Alcohol 15% Sodium Carboxymethyl Cellulose 5% Propylene Glycol 3% Ethanol 10% 5% Whitening Skin External Preparation of Example 3 Perfume, Preservative, Oxidant Appropriate Quantity Purified Water 62%

[0048]

The external preparation for whitening of the present invention has various L-ascorbic acids which are unstable as they are, and is extremely stabilized. Even when dispersed in an aqueous cosmetic such as a lotion, The present invention is characterized by constituting a stable W / O / W emulsification system without L-ascorbic acid contained therein being eluted by the emulsification phase inversion. In addition, when applied to the skin, it exerts a stable whitening effect and has high safety, so its clinical application is expected. Furthermore, a skin cosmetic containing these skin whitening external preparations is characterized in that L-stabilized by the whitening external preparation is stabilized.
Ascorbic acids maintain a whitening effect derived from their physiological functions for a long period of time. Therefore, the present invention makes it possible to simply supply an extremely stable skin whitening agent for skin whitening which has never existed before, and is of great industrial significance.

Claims (5)

[Claims] 1. A skin whitening external preparation comprising at least one selected from the group consisting of L-ascorbic acid and derivatives thereof, a nonionic surfactant and a neutral lipid. 2. The skin whitening preparation 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 1 μm or less. 3. The skin whitening external preparation according to claim 1, wherein the nonionic surfactant has an HLB of 4 or less. 4. The external preparation for whitening skin according to claim 1, wherein the melting point of the neutral lipid is 45 ° C. or lower. 5. A skin cosmetic comprising the external preparation for whitening skin according to any one of claims 1 to 4.