JP2019059792A - Skin external preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin external preparation having excellent viscosity stability and whitening effect by using caprylic hydroxamic acid. SOLUTION: Caprylic hydroxamic acid provides an external preparation for skin having excellent viscosity stability and whitening effect. [Selection diagram] None

Description

  The present invention relates to a skin external preparation containing capryl hydroxamic acid, a thickener and an organic acid.

Water-soluble polymers with thickening effects such as hyaluronic acid, carboxyvinyl polymer, hydroxypropyl methylcellulose and collagen are general-purpose materials for external skin preparations, and their excellent thickening and cushioning properties are extremely useful It is also used for the purpose of emulsion stabilization and viscosity stabilization of skin external preparations.
However, there is a problem that the viscosity is significantly reduced by blending the organic acid in order to adjust the weakly acidic skin external preparation which is preferred in recent skin external preparations.
Therefore, when a large amount of water-soluble polymer is blended for the purpose of stabilizing the viscosity, there is a problem that the feeling of use is deteriorated due to the twisting and sagging.
In addition, since these water-soluble polymers are easily hydrolyzed by light, there is a problem that when using them, it is necessary to provide a container with a light shielding property and use. For such measures, it is necessary to contain a coloring agent, an ultraviolet light absorber, etc. in the container, and the freedom of container preparation is lost, so development of a preparation having excellent light stability has been desired. .
On the other hand, capryl hydroxamic acid has a preservative effect (Reference 1), has a 5α reductase inhibitory activity (Reference 2), inhibits ADAM activity to improve wrinkles (Reference 3), and further with citric acid Similarly, it is known that it has a chelating effect of divalent and trivalent iron (References 4 and 5).
However, it has not been known that a combination of capryl hydroxamic acid and a thickener can provide a skin external preparation excellent in light stability.

WO2009-70736 JP, 2011-6462, A Republished 2009-123215 Japanese Patent Application Laid-Open No. 07-238037 Oil Chemistry, Vol. 32, No. 11, p 695-699, 1983

An object of the present invention is to provide a skin external preparation having high viscosity stability and further having a whitening effect.
Moreover, since the influence by light irradiation is suppressed, the skin external preparation of this invention may be able to be filled in the highly transparent container which is easy to perform quality control.

  The present inventors have prepared capryl into hyaluronic acid, derivatives thereof, salts thereof, carboxyvinyl polymers, derivatives thereof or salts thereof, water-soluble polymers such as hydroxypropyl methylcellulose and collagen, and organic acids or salts thereof. By blending a hydroxamic acid, it has been found that viscosity change can be suppressed, and a predetermined feeling of use can be maintained, and further, it has been found that it has a whitening effect, leading to the present invention.

Section. The skin external preparation containing 1 (A) capryl hydroxamic acid or its salt, (B) water-soluble polymer, and (C) organic acid or its salt.
Section. 2 (B) The water-soluble polymer is one or more selected from hyaluronic acid, a derivative thereof, a salt thereof, a carboxyvinyl polymer, a derivative thereof or a salt thereof, hydroxypropyl methylcellulose, collagen Skin external preparation as described.
Section. The skin external preparation according to Item 1 or 2, wherein the 3 (C) organic acid is one or more selected from succinic acid, citric acid, lactic acid, and salts thereof.
Section. The skin external preparation according to any one of Items 1 to 3, further comprising alkanediol.

  The external preparation for skin of the present invention has good viscosity stability and has a whitening effect.

  As the capryl hydroxamic acid or a salt thereof in the present invention, a commercially available product may be used as it is. Examples of commercially available products that can be used include, for example, trade names Spectrastat, SpectrastatE, Spectrastat G & G 2 (INOLEX) and the like.

In the present invention, the content of capryl hydroxamic acid 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. 0.01% by weight or more is even more preferable.
Moreover, 5 weight% or less is preferable, as for content of the capryl hydroxamic acid or its salt in this invention, 1 weight% or less is more preferable, 0.5 weight% or less is more preferable, 0.05 weight% or less is further more preferable. preferable. If it is the said range, it can mix | blend stably in a composition.

  Examples of water-soluble polymers in the present invention include hyaluronic acid, derivatives thereof, salts thereof, carboxyvinyl polymers, derivatives thereof or salts thereof, hydroxypropyl methylcellulose, collagen and the like, which are commercially available. You may use as it is. As commercial products which can be used, for example, hyaluronic acid, derivatives thereof or salts thereof, trade names: bio sodium hyaluronate HA9 N, bio sodium hyaluronate HA 12 N, bio sodium hyaluronate HA 20 N, bio hyaluronic acid SZE, acetylation Sodium hyaluronate (Shiseido), trade name: Hyaluronic sun HA-AM, Hyaluronic sun HA-QSE, Hyaluronic sun HA-QA, Hyaluronic sun HA-LQ, Hyaluronic sun HA-LQH, Hyaluronic sun solution HA-LQ1, Hyaluronic sun solution HA-LQH1, Hyaluronic sun solution HA -LQH1P, hyaloligo, hyalover, hyalover MPF, hyaloripia, hyalozinuk (Kewpie), trade name: Hyaluronic acid FCH-SU (Kibun Food Chemifa), quotient Name: Hyaluronic acid FCH-60, Hyaluronic acid FCH-120, Hyaluronic acid FCH-121C (Kikkoman Biochemifa), etc. can be exemplified, and as a carboxyvinyl polymer, its derivative, or a salt thereof, trade name: Carbobo Paul 934, Carbopol 940, Carbopol 1342 (BF Goodrich), trade name: Carbopol Ultrez 10, ETD 2050, Carbopol 980, Carbopol 981 (Japan Lubrizol), trade name: AQUPEC HV-505E (Sumitomo Seika) ), Trade name: Hibis Wako 104, Hi Bis Wako 105, Sinthalen K, Sinthalen L, (Wako Pure Chemical Industries, Ltd.), Junron (Nippon Pure Chemical Industries, Ltd.) etc., and as hydroxypropyl cellulose, trade name: HPC -L, HP C-H (Nippon Soda), trade name: Metrose 60SH4000, Metrose 65SH4000, HPC-LEP, HPC-LEG (Shin-Etsu Chemical Co., Ltd.), Sangerose 60L (Daido Chemical Industry Co., Ltd.), etc. can be exemplified. Brand name: Collagen tripeptide F (Gelice), Brand name: Promoice W-4000 (Naruwa Kasei), Brand name: Nippe Peptide FCP (Nippi), Brand name: Iquos HDL-500 C, Marin Gen SP-03 ( Nitta Gelatin), trade name: Sea Gem Multi-Collagen (Katakura Chiccalin), etc.

  The molecular weight of the hyaluronic acid, its derivative, or a salt thereof used in the present invention varies depending on the number and type of repeating units, and is not limited, but may be several hundred to several millions in weight average molecular weight . The weight-average molecular weight is preferably 100,000 to 5,000,000, more preferably 500,000 to 4,000,000, in terms of sufficiently exerting the effects of hyaluronic acid, a derivative thereof, or a salt thereof It is further preferable that it is -2.5 million.

The content of the water-soluble polymer in the present invention is preferably 0.00001% by weight or more, more preferably 0.0001% by weight or more, still more preferably 0.001% by weight or more, with respect to the total amount of the composition. More than .01 wt% is even more preferred.
Moreover, 5 weight% or less is preferable, as for content of the water-soluble polymer in this invention, 1 weight% or less is more preferable, and 0.5 weight% or less is still more preferable. If it is the said range, it can mix | blend stably in a composition.

In the present invention, the content of the water-soluble polymer to capryl hydroxamic acid is preferably 0.00001 parts by weight or more, more preferably 0.0001 parts by weight or more, and 0.001 parts by weight with respect to 1 part by weight of capryl hydroxamic acid. The above is more preferable, and 0.01 parts by weight or more is even more preferable. If it is the said range, the skin-whitening effect of a capryl hydroxamic acid or its salt can fully be exhibited.
In the present invention, the content of the thickener for capryl hydroxamic acid is preferably 10 parts by weight or less, more preferably 2 parts by weight or less, and further preferably 0.5 parts by weight or less per 1 part by weight of capryl hydroxamic acid. More preferable. If it is the said range, it can mix | blend stably in a composition.

  One or more kinds selected from organic acids and salts thereof in the present invention are succinic acid, sodium succinate, potassium succinate, triethanolamine succinate, citric acid, sodium citrate, potassium citrate, triethanolamine citrate, Examples thereof include lactic acid, sodium lactate, potassium lactate and triethanolamine lactate, and commercially available products may be used as they are.

The content of the organic acid or a salt thereof in the present invention is preferably 0.00005% by weight or more, more preferably 0.0001% by weight or more, and still more preferably 0.005% by weight or more, with respect to the total amount of the composition. 0.01 weight% or more is still more preferable. If it is the said range, the skin-whitening effect of a capryl hydroxamic acid or its salt can fully be exhibited.
Moreover, 5 weight% or less is preferable, as for content of the organic acid or its salt in this invention, 1 weight% or less is more preferable, and 0.5 weight% or less is still more preferable. If it is the said range, it can mix | blend stably in a composition.

In the present invention, the content of the organic acid or a salt thereof to capryl hydroxamic acid is preferably 0.00001 parts by weight or more, more preferably 0.0001 parts by weight or more, and 0.001 parts by weight with respect to 1 part by weight of capryl hydroxamic acid. More than part is more preferable, and 0.01 weight% or more is still more preferable. If it is the said range, the skin-whitening effect of a capryl hydroxamic acid or its salt can fully be exhibited.
The content of the organic acid or its salt relative to capryl hydroxamic acid in the present invention is preferably 40 parts by weight or less, more preferably 10 parts by weight or less, and further preferably 1 part by weight or less per 1 part by weight of capryl hydroxamic acid. Preferably, 0.5 parts by weight or less is even more preferable. If it is the said range, it can mix | blend stably in a composition.

  As the alkanediol in the present invention, pentanediol, hexanediol, octanediol and the like can be mentioned, and commercially available products may be used as they are. For example, as pentanediol, trade names HYDROLITE-5 (Simize), HYALU-CAGE SYSTEM (IRA srl), etc. can be exemplified, and as hexanediol, for example, trade name: KMO-6 (Osaka Organic Chemical Industry) HYDROLITE-60 (photosensitive company) and the like can be exemplified, and as octanediol, for example, trade name: HYDROLITE-8, audio eight (photosensitive company) and the like can be exemplified.

The content of the alkanediol in the present invention is preferably 0.00001% by weight or more, more preferably 0.0001% by weight or more, still more preferably 0.001% by weight or more, based on the total amount of the composition. % By weight is even more preferred.
Moreover, 5 weight% or less is preferable, as for content of alkanediol in this invention, 1 weight% or less is more preferable, and 0.5 weight% or less is still more preferable. If it is the said range, it can mix | blend stably in a composition.

In the present invention, the content of alkanediol relative to capryl hydroxamic acid is preferably 0.00001 parts by weight or more, more preferably 0.0001 parts by weight or more, and 0.0005 parts by weight or more per 1 part by weight of capryl hydroxamic acid. More preferably, 0.001 parts by weight or more is even more preferable.
Further, the content of alkanediol to capryl hydroxamic acid in the present invention is preferably 5 parts by weight or less, more preferably 1 part by weight or less, and still more preferably 0.5 part by weight or less based on 1 part by weight of capryl hydroxamic acid. preferable. If it is the said range, it can mix | blend stably in a composition.

Base or Carrier In the present invention, the composition for external use can contain other known bases or carriers used for cosmetics and quasi-drugs as long as the effects of the present invention are not impaired. The base or the carrier can be used alone or in combination of two or more.

  As a base or a carrier, such as paraffin, liquid paraffin, squalane, white wax, gelled hydrocarbon (such as plastibase), ozokerite, ceresin, vaseline, hard fat, microcrystalline wax, α-olefin oligomer, light liquid paraffin, etc. Hydrocarbons; Fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, isostearic acid; glyceryl tri-2-ethylhexanoate (trioctanoin), tri (caprylic acid / capric acid) glyceryl Tri-fatty acid glycerides; higher alcohols such as cetanol, stearyl alcohol, behenyl alcohol; methyl polysiloxane, highly polymerized methyl polysiloxane, dimethylsiloxane methyl (polyoxyethylene) siloxane methyl Polyoxypropylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxyethylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxypropylene) siloxane copolymer, polyoxyethylene / methylpolysiloxane copolymer, poly ( Oxyethylene / oxypropylene) / methylpolysiloxane copolymer, dimethylsiloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl acrylate copolymer methylpolysiloxane ester, cross-linked methyl Polysiloxane, Cross-linked methyl phenyl polysiloxane, Cross-linked polyether modified silicone, Cross-linked alkyl polyether modified silicone, Cross-linked alkyl modified silicone, decamethyl cyclopenta Silicones such as siloxane, ethyltrisiloxane, methyltrimethicone, methylsiloxane network polymer, polyoxyethylene / methylpolysiloxane copolymer, methylhydrogenpolysiloxane, triethoxysilylethyl polydimethylsiloxyethylhexyl dimethicone, dimethylpolysiloxane Oils: glycol acetates such as ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol diacetate, hexylene glycol diacetate, and 2-methyl-2-propene-1,1-diol diacetate Tart; triethylene glycol divalerate, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, 2,2,4-trimethyl-1,3-pentanediol diiso Glycol esters such as thiolates; ethylene glycol diacrylates, diethylene glycol diacrylates, propylene glycol monoacrylates, 2,2-dimethyl-trimethylene glycol diacrylates, and 1,3-butylene glycol diacrylates Glycol acrylate; glycol dinitrate such as ethylene glycol dinitrate, diethylene glycol dinitrate, triethylene glycol dinitrate, and propylene glycol dinitrate; 2,2 '-[1,4-phenylenedioxy] diethanol; ethyl cellulose, hydroxy Cellulose derivatives such as propyl cellulose and hydroxypropyl methyl cellulose; polyvinyl pyrrolidone; carrageenan; polyvinyl butyra Polyethylene glycol; dioxane; butylene glycol adipate polyester; isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, esters such as tetraerythanoate tetra-ethylhexanoate; dextrin , 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 monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol Monobutyl ether, propylene glycol Examples thereof include glycol ethers such as Cole monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether and dipropylene glycol monopropyl ether; and aqueous bases such as water.

  Among them, hydrocarbons (in particular, α-olefin oligomers, squalane, light liquid paraffin, liquid paraffin), trifatty acid glycerides (in particular, glyceryl tri-2-ethylhexanoate, tri (caprylic acid / capric acid) glyceryl), higher alcohols (Especially cetanol, stearyl alcohol, behenyl alcohol) silicone oil (especially methylpolysiloxane, alkyl acrylate copolymer methylpolysiloxane ester, cross-linked methylpolysiloxane, decamethylcyclopentasiloxane, ethyltrisiloxane, methyltrimethicone Methyl siloxane network polymer, polyoxyethylene methylpolysiloxane copolymer, methyl hydrogen polysiloxane, triethoxysilylethyl polydimethylsiloxyethylhexyl dimer Cones, dimethylpolysiloxanes, esters (in particular, isononyl isononate, tetra-ethylhexanoate pentaerythritol), polysaccharides (in particular, dextrin, maltodextrin), glycol ethers (in particular, diethylene glycol monoethyl ether), water Is preferred.

  Additives In the present invention, the composition for external use is a known additive to be added to cosmetics and quasi-drugs as long as the effects of the present invention are not impaired, such as thickeners, surfactants, preservatives, A pH adjuster, a chelating agent, a stabilizer, an irritation reducing agent, an antiseptic, a coloring agent, a dispersing agent, a fragrance, a pearl luster imparting agent and the like can be added. The additives may be used alone or in combination of two or more.

  As a thickener, oil-soluble polymers, such as dextrin fatty acid ester, can be mentioned, for example.

  Examples of surfactants include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, diglycerol sorbitan tetra-2-ethylhexylate Sorbitan fatty acid esters; Glyceryl fatty acid such as glyceryl monostearate and glycerin monostearate; Polyglyceryl monostearate, polyglyceryl monoisostearate and polyglyceryl fatty acid such as polyglyceryl diisostearate; Propylene glycol monostearate Propylene glycol fatty acid esters such as: polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor Cured castor oil derivatives such as silicone oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), polyoxyethylene hydrogenated castor oil 80, etc .; monolauric acid polyoxyethylene (20) sorbitan (polysorbate 20) Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene monostearate (20) sorbitan (polysorbate 60), monooleate polyoxyethylene (20) sorbitan (polysorbate 80), isostearate polyoxyethylene (20) sorbitan Polyoxyethylene mono-cocoyl fatty acid glyceryl; glycerin alkyl ether; alkyl glucoside; polyoxyalkylene alkyl ether such as polyoxyethylene cetyl ether; stearylamine, oleyl Amines such as min; polyoxyethylene / methylpolysiloxane copolymers, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, silicone surfactants such as PEG-9 polydimethylsiloxyethyl dimethicone, etc. .

  Among them, glycerin fatty acids (especially glyceryl monostearate), polyglycerin fatty acids (especially polyglyceryl monostearate), hydrogenated castor oil derivatives (especially polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxy Ethylene hydrogenated castor oil 60 (HCO-60)), polyoxyethylene sorbitan fatty acid esters (in particular, polyoxyethylene (20) sorbitan isostearate, sorbitan monostearate (20) sorbitan (polysorbate 60)), polyoxy acid Alkylene alkyl ether (especially polyoxyethylene cetyl ether), silicone surfactant (especially polyoxyethylene / methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, PE -9 polydimethylsiloxyethyl dimethicone) is preferred.

  Preservatives and preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, parahydroxybenzoic acid Benzyl, methyl parahydroxybenzoate, phenoxyethanol and the like can be mentioned. Among them, methyl parahydroxybenzoate, propyl parahydroxybenzoate and phenoxyethanol are preferable.

pH
The pH of the composition for external use of the present invention is preferably 2.5 or more, more preferably 3 or more, and still more preferably 4 or more. Further, 9 or less is preferable, 8.5 or less is more preferable, and 8 or less is even more preferable. If it is the said range, a stable formulation can be created.

Formulation form The external use composition of the present invention is a pharmaceutical or physiological agent which is usually used for external use composition such as pharmaceuticals, quasi-drugs or cosmetics, for example, capryl hydroxamic acid and its salts, water-soluble polymer and organic acid. For pharmaceuticals, quasi-drugs, or cosmetics, mixed with an additive or vehicle generally used in an externally applied composition such as pharmaceuticals, quasi-pharmaceuticals, or cosmetics if necessary. The composition can be used as a composition for external use.

The form of the composition for external use for pharmaceuticals is not particularly limited, and examples thereof include solutions, suspensions, emulsions, creams, ointments, gels, liniments, lotions, and aerosols. These preparations can be produced according to the method described in the 16th revised Japanese Pharmacopoeia General Rules, and the like.
Also when it is set as the quasi-drug external product or the external composition for cosmetics, it can be made the same form as said pharmaceutical. Moreover, the sheet agent etc. which made the chemical | medical solution impregnate a stick agent and a nonwoven fabric other than that are mentioned.

  Specifically for use as a composition for external use for quasi-drugs or cosmetics, for example, lotions, emulsions, gels, creams, cosmetics, sunscreen cosmetics, packs, masks, hand creams, lips Foundation cosmetics such as creams, body lotions and body creams; makeup cosmetics such as foundations, lipsticks, teak colors and eye colors; and facial cleansers, makeup removers, body shampoos, shampoos, rinses and treatments Such cosmetics for washing etc. are mentioned. In addition, there is also a multifunctional preparation in which at least two or more of the preparation functions of the basic cosmetic, the makeup cosmetic, the cleansing cosmetic and the like are combined into one preparation.

Other Active Ingredients The composition for external use of the present invention can contain other active ingredients as long as the effects of the present invention are not impaired.
Specific examples of the other active ingredients include, for example, moisturizing ingredients, antibacterial or bactericidal ingredients, vitamins, peptides or derivatives thereof, amino acids or derivatives thereof, cell activating ingredients, antiaging ingredients, circulation promoting ingredients, keratin softening ingredients, And astringent components, ultraviolet light protective components and the like.

As the moisturizing ingredient, for example, polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, dipropylene glycol, sorbitol, xylitol, erythritol and diglycerin; such as glucose, maltose and trehalose Saccharides; heparin analogues, sodium chondroitin sulfate, collagen, elastin, keratin, chitin, and high molecular compounds such as chitosan;
Amino acids such as glycine and aspartic acid; natural moisturizing factors such as sodium lactate, urea and sodium pyrrolidone carboxylate; lipids such as ceramide, cholesterol and phospholipids; and chamomile extract, hamamelis extract, tea extract and shiso extract Plant extracts and the like.

As the antibacterial or bactericidal component, for example, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, sulfur, resorcinol, ethanol, benzethonium chloride, adapalene, benzoyl peroxide, clindamycin, cresol, gluconic acid and derivatives thereof,
Popidone iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101, photosensitizer 201, glycerin fatty acid ester, alkyldiaminoglycine hydrochloride, chlorhexidine gluconate, zinc paraphenol sulfonate, azelaic acid, etc. Can be mentioned.

  As vitamins, for example, vitamin B2s such as riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate sodium ester, and riboflavin tetranicotinate; nicotinic acid Nicotinic acid amide, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, and nicotinic acids such as 1- (4-methylphenyl) ethyl nicotinate; methyl hesperidin, ergocalciferol, cholecalciferol etc. Vitamin Ds; Vitamin Ks such as phylloquinone and farnoquinone; dibenzoyl thiamine, dibenzoyl thiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate Acid salt, thiamine lauryl hydrochloride, thiamine nitrate, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, Vitamin B1s such as thiamine triphosphate and thiamine triphosphate monophosphate; vitamin B12s such as cyanocobalamin, hydroxocobalamin, and deoxyadenosyl cobalamin; folic acid, pteroyl glutamic acid etc; pantothenic acid, pantothenic acid Acid calcium, pantothenyl alcohol (panthenol), D-panthesain, D-panthetin, coenzyme A, and pantothenic acid such as pantothenylethyl ether; biotin such as biotin or biotin And vitamin-like agents such as carnitine, ferulic acid, α-lipoic acid, orotic acid, γ-oryzanol, and the like.

  Examples of peptides or derivatives thereof include keratinolytic peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin degrading peptides, collagenolytic peptides, hydrolyzed collagen, hydroxypropyl ammonium chloride hydrolyzed collagen, elastin Degraded peptide, Conchiolin degrading peptide, Hydrolyzed conchiolin, Silk protein degradable peptide, Hydrolyzed silk, Lauroyl hydrolyzed silk sodium, Soy protein degradable peptide, Hydrolyzed soy protein, Wheat protein, Wheat protein degradable peptide, Hydrolyzed wheat protein, Casein Degraded peptides, as well as acylated peptides (palmitoyl oligopeptide, palmitoyl pentapeptide, palmitoyl tetrapeptide, etc.) and the like can be mentioned.

  Examples of amino acids or derivatives thereof include betaine (trimethylglycine), proline, hydroxyproline, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine Leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine and the like.

  Examples of cell activation components include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid; vitamins such as thiamine, riboflavin and pantothenic acids; α-hydroxy acids such as glycolic acid and lactic acid; tannins and flavonoids Saponin, allantoin, and photosensitive element No. 301.

  Examples of the antiaging component include pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, and mevalonolactone.

  Examples of the blood circulation promoting active ingredient include plants (for example, Panax ginseng, Ashitaba, Arnica, Ginkgo biloba, Ginkgo biloba, Ginkgo biloba, Ginkgo biloba, Ginkgo biloba, Lobster chamomile, Carrot, Gentiana, Burdock, Rice, Hawthorn, Shiitake, Hawthorn, Hyacinopsis, Senkyu, assembly, thyme, chopsticks, chimbi, toenoki, toenou, spruce, carrot, garlic, butcherbroom, grape, button, marronie, melissa, yuzu, yokinin, rosemary, rosehip, chimpo, touki, spruce, peach, anise , Walnut, and corn); and glucosyl hesperidin and the like.

  Examples of the emollient component include urea, salicylic acid, glycolic acid, fruit acid, phytic acid, and sulfur.

  Examples of the astringent component include zinc paraphenol sulfonate, zinc oxide, menthol, and ethanol.

  Examples of UV protective components include inorganic compounds such as zinc silicate, cerium silicate, titanium silicate, zinc oxide, zirconium oxide, cerium oxide, titanium oxide, iron oxide, and such inorganic compounds as hydrated silica, anhydrous silica Coated with inorganic powder such as acid, aluminum hydroxide, mica and talc, compounded with resin powder such as polyamide, polyethylene, polyester, polystyrene and nylon, and treated with silicone oil and fatty acid aluminum salt etc And the like.

  The other active ingredients can be used singly or in combination of two or more.

  In the present invention, the whitening effect refers to improvement, suppression, reduction, prevention, prevention, or delay of skin pigmentation caused by melanin pigments and the like which are particularly related to skin dullness, melasma and the like. . The above-mentioned whitening agent has a whitening action to keep the skin white.

  In the present invention, the melanin production inhibitor refers to one that inhibits, suppresses, prevents, prevents or reduces melanin production.

Method of Use The composition for external use of the present invention varies depending on the condition, age, sex and the like of the skin to be used, and may be, for example, the following method. That is, an appropriate amount (for example, about 0.05 to 5 g) may be applied to the skin several times a day (for example, about 1 to 5 times, preferably 1 to 3 times). In addition, external use of capryl hydroxamic acid so that the daily usage amount is, for example, about 0.0005 to 0.05 g, preferably about 0.001 to 0.02 g, more preferably about 0.002 to 0.01 g The composition may be applied.
The application period is not particularly limited, and may be, for example, about 2 weeks to 6 months, preferably about 1 to 6 months.
The composition for external use of the present invention can be suitably used for people with various skin diseases and skin troubles in expectation of the physiological activity of capryl hydroxamic acid. In particular, a person having wrinkles and snails, a person whose skin texture is disordered, and a person having sensitive skin are suitable targets. In addition, for the prevention of skin problems due to non-photoaging in particular, persons with normal skin are also suitable for use. Furthermore, it can be suitably used as a sunscreen cosmetic for protecting the skin from ultraviolet light, preventing sunburn, and the like.

  Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited to these examples.

Test Example 1 Viscosity Stability Test Each test solution was prepared according to Tables 1-1 to 2-3. Each 10 mL of the test solution is filled in a glass screw vial (volume 10 mL), and a light stability test device (“Light-Tron LT-120 D3CJ”, manufactured by Nagano Science Co., Ltd.) is used, and D65 fluorescent lamp is used as a light source After light irradiation was performed at 5000 lx for about 120 hours (total 600,000 lx hr) under 25 ° C. conditions, the viscosity at 25 ° C. was measured under the following measurement conditions.
The measurement is based on the test method of "(2) cone-plate rotation viscometer (corn plate viscometer)" described in the 16th revision Japanese Pharmacopoeia General Test Method Viscosity Measurement Method 2 Method Rotational Viscometer Method Then, RE 85 (Touki Sangyo Co., Ltd.) was used.
Measurement conditions: Temperature 25 ° C, rotation speed 20rpm, rotor 1 ° 34 'x 24
Measurement value The viscosity of the average value of what measured the viscosity for every one minute to 3 minutes was made into the measurement value.
The viscosity of each of the unirradiated sample and the irradiated sample was measured, and the viscosity of the unirradiated sample was 100, and the viscosity after irradiation was expressed as a relative viscosity as a viscosity retention rate, and the amount of change was compared.
Viscosity retention (%) = (viscosity of irradiated sample) / (viscosity of unirradiated sample) x 100
Basically, as shown in FIG. 1, put a sample in the gap of angle α between cone 1 and flat disk 2 and rotate cone 1 or flat disk 2 at constant angular velocity ω or torque T The torque or angular velocity received by the flat disk 2 or the cone 1 when the steady state is reached is measured, and the viscosity η of the sample is calculated by the following equation.
η = 100 × (3α / 2πR3) · (T / ω)
η: Viscosity of the sample (mPa · s) (Pa · s = 10 ³ mPa · s)
α: angle (rad) between flat disk 2 and cone 1
π: Circle ratio R: Radius of cone (cm)
T: Torque acting on flat disk 2 or one conical surface (10 ^-7 N · m)
ω: Angular velocity (rad / s)
Figure 1

表１−２ 単位：ｗ／ｗ％

表１−３ 単位：ｗ／ｗ％

Table 1-1 Unit: w / w%

Table 1-2 Unit: w / w%

Table 1-3 Unit: w / w%

In citric acid and succinate buffer solutions, the viscosity of sodium hyaluronate and hydroxypropyl methylcellulose decreased, but the viscosity decrease was suppressed by blending capryl hydroxamic acid. However, viscosity decrease of sodium hyaluronate and hydroxypropyl methylcellulose did not occur in the phosphate buffer, and therefore, there was no change even when compounding with capryl hydroxamic acid.
The stability was further improved by adding 1,2-octanediol.

表２−２ 単位：ｗ／ｗ％

クエン酸、コハク酸、乳酸の濃度を低くした時でも、ヒアルロン酸ナトリウム、ヒドロキシプロピルメチルセルロース、カルボキシビニルポリマーと配合すると粘度低下が起きたが、カプリルヒドロキシサム酸を配合する事により粘度安定性が良くなった。 Table 2-1 Unit: w / w%

Table 2-2 Unit: w / w%

Even when the concentration of citric acid, succinic acid and lactic acid was lowered, the viscosity decreased when it was blended with sodium hyaluronate, hydroxypropyl methylcellulose and carboxyvinyl polymer, but the viscosity stability is good by blending with capryl hydroxylamic acid became.

Test Example 2 Melanin production suppression evaluation A melanin production suppression test was performed using mouse-derived melanoma cells.
Specifically, mouse-derived melanoma cells are seeded in a 6-well plate at a density of 1.5 × 10 ⁴ cells / well using DMEM medium containing 10% FBS, 37 ° C., 5% carbon dioxide and 95% The cells were cultured for 1 day in an air environment. Then, while performing medium exchange, add 15 μL each of capryl hydroxamic acid prepared with ethanol to each concentration or ethanol as a control, and further adjust citric acid, collagen, and sodium hyaluronate to 60 μl each adjusted to each concentration with distilled water. Each ochL was added. After culturing for 3 days under the same conditions, the supernatant was removed and washed once with PBS (-). Thereafter, 400 μL of 5N NaOH was added, and cells were lysed by heating at 60 ° C. for 2 hours, and the amount of melanin production was determined by measuring the absorbance at 475 nm. This was made into a measured value (test sample measured value, control measured value), and it calculated | required by following Formula (Formula 1) as a melanin production rate with respect to a control value.
In addition, 25 μL of the cell lysate was collected in a 96-well plate, and the amount of protein was measured using a BCA protein assay kit to determine the cell viability. This was used as a measurement value (test sample measurement value, control measurement value), and it calculated | required by following Formula (Formula 2) as a cell survival rate with respect to a control value.
Furthermore, the melanin production rate per unit protein was determined by Formula 3 by dividing the melanin production rate determined by Formula 1 by the corresponding cell viability.
Formula 1: melanin production rate = [(absorbance of test substance at 475 nm) / (absorbance of control at 475 nm)] × 100 (%)
Formula 2: Cell viability = [(the amount of protein of the test substance) / (the amount of protein of the control)] x 100 (%)
Formula 3: melanin production rate per unit protein (%) = (melanin production rate determined by formula 1) / (cell viability of the corresponding test example)

表３−２ 単位蛋白あたりのメラニン産生率

各成分、２成分での組み合わせではメラニン産生は抑制されなかったが、３成分を含むことで、メラニン産生が抑制された。 Table 3-1 Melanin production rate per unit protein

Table 3-2. Melanin production rate per unit protein

Although the combination of each component and two components did not suppress melanin production, the inclusion of three components suppressed melanin production.

An example of prescription is shown below. The preparation method conforms to a conventional method.
Prescription example 1 (skin lotion)
Glycerin 3
Ethanol 3
Capryl hydroxy samo acid 0.1
Sodium hyaluronate 0.1
Succinic acid 0.3
Sodium succinate 0.5
Total purified water 100% by weight remaining

Prescription example 2 (gel)
Glycerin 5
1,3-butylene glycol 5
Carboxy vinyl polymer 0.3
Arginine 0.3
Polyoxyethylene Cured Castor Oil 0.5
Capryl hydroxylamic acid 0.05
Lactic acid (70% solution) 0.5
Total purified water 100% by weight remaining

Prescription example 3 (skin lotion)
Capryl hydroxylamic acid 0.05
Tranexamic acid 2
Salicylic acid 0.1
Sodium hyaluronate 0.2
Concentrated glycerin 2
1,3-butylene glycol 10
Polyoxypropylene methyl glucoside 0.2
Acetylated sodium hyaluronate 0.01
Hydroxyethyl cellulose 0.05
Sodium citrate 0.1
Flavoring agent Appropriate amount of purified water Total 100% by weight

Prescription example 4 (skin lotion)
Ascorbic acid glucoside 2
Salicylic acid 0.05
Concentrated glycerin 3
Propylene glycol 5
Sorbitol 1
Polyoxypropylene methyl glucoside 0.5
Polyoxyethylene Cured Castor Oil 0.1
Carboxy vinyl polymer 0.05
2-Methacryloyloxyethyl phosphoryl choline / butyl methacrylate copolymer
0.5
Xanthan gum 0.05
Vinylpyrrolidone-styrene copolymer emulsion 0.3
Hydrolyzed hyaluronic acid 0.1
Phosphoric acid L-ascorbyl magnesium 0.01
Capryl hydroxy samo acid 0.1
Chelating agent (sodium edetate) suitable amount citric acid 0.05
Flavoring agent Appropriate amount of purified water Total 100% by weight

Prescription example 5 (milky lotion)
Dipotassium glycyrrhizinate 0.1
Arbutin 0.1
Dipropylene glycol 5
1,3-butylene glycol 8
Concentrated glycerin 3
Glycerin monostearate 1
Carboxy vinyl polymer 0.2
Xanthan gum 0.05
Meadow foam oil 5
Glyceryl tri 2-ethylhexanoate 5
Methylpolysiloxane 1
Triethanolamine 0.1
Tocopherol 0.1
Acetylated sodium hyaluronate 0.05
Capryl hydroxylamic acid 0.05
Succinic acid 0.1
Chelating agent (sodium edetate) Appropriate amount of flavoring agent Suitable amount of purified water Total 100% by weight

Prescription example 6 (cream)
Tranexamic acid 1
Arbutin 3
Sodium hyaluronate 0.15
Dipropylene glycol 8
Diglycerin 5
Concentrated glycerin 3
Hydroxyethylurea 3
Polyoxyethylene sorbitan isostearate 0.5
Glycerin monostearate 0.4
Setostearyl Glucoside ・ Setostearyl Alcohol 1.5
Acrylic acid / methacrylic acid alkyl copolymer 0.5
Meadowfoam oil 0.5
Squalane 3
Tri (Caprylic / Capric) Glyceryl 1.5
Methylpolysiloxane 1
Behenyl alcohol 0.2
Stearyl alcohol 0.3
Xanthan gum 0.2
Sodium hydroxide 0.2
Capryl hydroxylamic acid 0.05
Sodium lactate 0.1
Chelating agent (sodium edetate) Appropriate amount of flavoring agent Suitable amount of purified water Total 100% by weight

  The composition for external use of the present invention contains capryl hydroxylamic acid, a water-soluble polymer, and an organic acid or a salt thereof, and is excellent in viscosity stability and whitening effect, and thus has high commercial value.

Claims (1)

  The invention described in the specification.