Collagen production promoters and topical skin preparations containing them

Abstract

The present invention provides a collagen production promoter and a topical skin preparation containing the same. [Solution] According to one embodiment, a collagen production promoter comprising a compound represented by formula (I) or a salt thereof is provided: TIFF2026087505000015.tif31163 [In formula (I), R represents an alkyl group having 1 to 4 carbon atoms.]

Description

Technical Field

[0001] The present invention relates to a collagen production promoter and a topical skin preparation containing the same.

Background Art

[0002] When the skin is exposed to ultraviolet rays contained in sunlight, ultraviolet lamps, etc., the collagen in the skin is decomposed, resulting in loss of firmness and elasticity, leading to skin aging such as wrinkles and sagging. Collagen involved in the firmness and elasticity of the skin is produced by fibroblasts present in the dermis. It is considered that when degrading enzymes are produced by ultraviolet rays, the collagen in the dermis, which is the base supporting the skin, is decomposed, and the structure collapses, resulting in loss of firmness and elasticity and the occurrence of wrinkles and sagging.

[0003] It is known that promoting the production of collagen is effective in improving wrinkles and sagging. Known active ingredients for promoting the production of collagen include glycolic acid, magnesium ascorbyl phosphate, or their derivatives or various plant extracts.

[0004] Patent Document 1 discloses a topical skin preparation effective for preventing and improving skin aging symptoms, which contains one or more selected from the group consisting of α-hydroxy acids, their salts and derivatives, and a protein obtained by extraction from eggshell membrane. Patent Document 2 discloses a topical skin preparation effective for preventing skin aging, which contains one or more selected from the group consisting of α-hydroxy acids, their salts and derivatives, and / or a protein extracted from eggshell membrane, and sphingolipids and / or sphingoglycolipids. Patent Document 3 discloses a skin cosmetic and a topical skin preparation effective for preventing skin aging, which contain α-hydroxyacetic acid as a dermal fibroblast proliferator.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

[0006] In recent years, the harmful effects of ultraviolet radiation have become widely recognized, and there is a need for novel collagen production promoters that can safely suppress skin aging caused by ultraviolet radiation and other factors. Therefore, the present invention aims to provide a collagen production promoter and a topical skin preparation containing the same. [Means for solving the problem]

[0007] The inventors of the present invention have diligently studied to solve the above problems and have found that a compound having a predetermined structure or a salt thereof has a collagen production promoting effect, thereby completing the present invention. The present invention includes the following embodiments. [1] Collagen production promoters containing compounds represented by formula (I) or salts thereof: [ka] [In formula (I), R represents an alkyl group having 1 to 4 carbon atoms.] [2] The collagen production promoter according to [1], wherein R in formula (I) is a methyl group. [3] A collagen production promoter described in [1] or [2] that further has one or more of the following effects (a) to (g): (a) Dissolving ability for oils (b) Solubility for oils and fats (c) Chemical peeling ability (d) Ability to remove acne bacteria (e) Melanin production inhibitory ability (f) Increased mRNA expression of Type I collagen (g) Antioxidant effect. [4] A collagen production promoter according to any one of [1] to [3], comprising 20 mM or more of the compound represented by formula (I) or a salt thereof. [5] A topical skin preparation containing a collagen production promoter as described in any of [1] to [4]. [6] The topical skin preparation according to [5], wherein the compound represented by formula (I) or a salt thereof is contained in an amount of 0.001 to 50% by weight relative to the topical skin preparation. [7] The topical skin preparation according to [5] or [6], further comprising one or more additives selected from the group consisting of thickeners, pH adjusters, preservatives, and antioxidants. [8] The topical skin preparation according to [7], wherein each of the additives is contained in an amount of 0.01 to 20% by weight relative to the topical skin preparation. [9] A topical skin preparation according to any of [5] to [8], wherein the pH is 0.5 to 12.

[10] A topical skin preparation according to any of [5] to [9], which is an anti-wrinkle or anti-sagging cosmetic.

[11] The anti-wrinkle or anti-sagging cosmetic is selected from the group consisting of lotions, creams, emulsions, gels, serums, facial cleansers, soaps, ointments, packs, and foundations, and is a topical skin preparation as described in

[10] . [Effects of the Invention]

[0008] According to the present invention, a collagen production promoter and a topical skin preparation containing the same can be provided. [Brief explanation of the drawing]

[0009] [Figure 1] This figure shows the results of the cytotoxicity test in Example 1. [Figure 2] This figure shows the results of the collagen production promoting effect test in Example 2. [Figure 3] This figure shows the measurement results of Type I collagen gene expression in Example 2-2. [Figure 4] This figure shows the measurement results of the antioxidant activity (NAD+ / NADH value) in Example 2-3-1. [Figure 5]It is a diagram showing the measurement results of the antioxidant action (intracellular ROS value) of Example 2-3-2. [Figure 6] It is a diagram showing the results of the measurement of the melanin production rate of Example 4.

Mode for Carrying Out the Invention

[0010] Hereinafter, embodiments of the present invention will be described in detail. [1] Collagen production promoter According to one embodiment of the present invention, there is provided a collagen production promoter containing a compound represented by the following formula (I) or a salt thereof:

Chemical formula

[0011] The alkyl group having 1 to 4 carbon atoms may be linear or branched, and examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a t-butyl group, etc. R is preferably a methyl group, an ethyl group, or an isopropyl group, more preferably a methyl group or an ethyl group, and particularly preferably a methyl group. The compound of formula (I) when R is a methyl group is 2-hydroxyisobutyric acid, and hereinafter, this will be referred to as "methyl lactic acid". As the salt of the compound of formula (I), without being limited thereto, pharmaceutically acceptable salts can be used. Examples of such salts include sodium salts, potassium salts, magnesium salts, calcium salts, etc. Among them, sodium salts or potassium salts are preferred.

[0012] The collagen production promoter contains a compound represented by formula (I) or a salt thereof in an amount of 2.5 mM (mmol / l) or more, 5 mM or more, 10 mM or more, 20 mM or more, or 40 mM or more. Preferably, the collagen production promoter contains a compound represented by formula (I) or a salt thereof in an amount of 20 mM or more or 40 mM or more. For example, the collagen production promoter contains a compound represented by formula (I) or a salt thereof in an amount of 20 mM to 1000 mM, 20 mM to 800 mM, 20 mM to 600 mM, 20 mM to 400 mM, or 20 mM to 200 mM.

[0013] The collagen production promoter according to the embodiment can effectively promote collagen production. Furthermore, the topical skin preparation containing the collagen production promoter is stable, highly safe, and exhibits excellent anti-wrinkle or anti-sagging effects and / or whitening effects.

[0014] [2] Topical skin preparations According to another embodiment of the present invention, a topical skin preparation comprising the above-mentioned collagen production promoter is provided. The compound represented by formula (I) or its salt is included in the topical skin preparation in amounts such as 0.001 to 50% by weight, 0.001 to 5% by weight, 0.001 to 1% by weight, 0.001 to 0.1% by weight, or 0.01 to 0.1% by weight. By including the compound of formula (I) or its salt in such amounts, a good collagen production promoting effect can be obtained. The content of the compound of formula (I) or its salt can be appropriately set depending on the type and use of the topical skin preparation.

[0015] By utilizing its collagen production-promoting effect, the above-mentioned topical skin preparation can be used as an anti-wrinkle or anti-sagging cosmetic and / or a whitening cosmetic. The anti-wrinkle or anti-sagging cosmetic and / or whitening cosmetic is not particularly limited as long as it is applied to the skin, but examples include lotions, creams, emulsions, gels, serums, facial cleansers, soaps, ointments, masks, foundations, etc. Such anti-wrinkle or anti-sagging cosmetic and / or whitening cosmetic can be manufactured according to commonly used formulation methods.

[0016] The topical skin preparation may contain additives commonly used in cosmetics and pharmaceuticals, in addition to the collagen production promoter according to the embodiment. Examples of such additives include powder components, liquid oils and fats, solid oils and fats, waxes, hydrocarbon oils, higher fatty acids, higher alcohols, synthetic ester oils, silicones, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, humectants, water-soluble polymer compounds, thickeners, film-forming agents, UV absorbers, UV blockers, preservatives, metal ion chelating agents, lower alcohols, polyhydric alcohols, sugars, amino acid derivatives, organic amines, synthetic resin emulsions, pH adjusters, skin nutrients, vitamins, antioxidants, antioxidant aids, fragrances, water, etc., and these can be selected and blended as needed. In particular, the topical skin preparation according to the embodiment preferably contains one or more additives selected from the group consisting of thickeners, pH adjusters, preservatives, and antioxidants. Furthermore, other medicinal or physiologically active ingredients such as vitamins, skin activators, blood circulation promoters, resident bacteria control agents, free radical scavengers, anti-inflammatory agents, other whitening agents, and bactericides may be added as needed.

[0017] The above additives may be used individually or in combination. The amount of additives used is not particularly limited, but for example, they may be added to the topical skin preparation in amounts of 0.01 to 20% by weight, 0.01 to 10% by weight, 0.01 to 5% by weight, or 0.01 to 1% by weight, respectively (per additive). Furthermore, it is preferable that the total amount of additives added to the topical skin preparation be 0.1 to 50% by weight, 0.1 to 20% by weight, 0.1 to 10% by weight, or 0.1 to 5% by weight. By including the additives in such amounts, the effects of the additives are achieved without interfering with the effects of the active ingredient, the compound of formula (I) or its salt.

[0018] The following are specific examples of additives. Powder components include, for example, talc, kaolin, mica, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, tungstate metal salts, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (calcined gypsum), calcium phosphate, hydroxyapatite, ceramic powder, metal soaps (zinc myristate, calcium palmitate, aluminum stearate), polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, styrene-acrylic acid copolymer resin powder, cellulose powder, and other organic powders; inorganic white pigments such as titanium dioxide and zinc oxide; inorganic red pigments such as iron oxide (red iron oxide) and iron titanate; inorganic purple pigments such as carbon black, mango violet, and cobalt violet; cobalt titanate Inorganic green pigments such as t; inorganic blue pigments such as ultramarine and Prussian blue; pearl pigments such as titanium dioxide-coated mica, titanium dioxide-coated bismuth oxychloride, titanium dioxide-coated talc, colored titanium dioxide-coated mica, bismuth oxychloride, and fish scale foil; metal powder pigments such as aluminum powder and copper powder; Red No. 201, Red No. 202, Red No. 204, Red No. 205, Red No. 220, Red No. 226, Red No. 228, Red No. 405 Examples include organic pigments such as orange 203, orange 204, yellow 205, yellow 401, and blue 404; organic pigments such as zirconium, barium, or aluminum lake, such as red 3, red 104, red 106, red 227, red 230, red 401, red 505, orange 205, yellow 4, yellow 5, yellow 202, yellow 203, green 3, and blue 1; and natural pigments such as chlorophyll and β-carotene. However, these powder components may be any powder that can be used in general cosmetics and are not limited to the above components.

[0019] Examples of liquid oils include avocado oil, camellia oil, evening primrose oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, wheat germ oil, castor oil, linseed oil, safflower oil, cottonseed oil, soybean oil, peanut oil, tea seed oil, rice bran oil, jojoba oil, wheat germ oil, triglycerin, glyceryl trioctanoate, and glyceryl triisopalmitate.

[0020] Examples of solid fats and oils include cocoa butter, coconut oil, horse fat, hydrogenated coconut oil, palm oil, beef tallow, sheep fat, hydrogenated beef tallow, palm kernel oil, lard, beef bone fat, Japanese wax kernel oil, hydrogenated oil, beef tallow, Japanese wax, and hydrogenated castor oil.

[0021] Examples of waxes include beeswax, candelilla wax, cotton wax, rice bran wax, carnauba wax, bayberry wax, privet wax, whale wax, lanolin, lanolin acetate, liquid lanolin, isopropyl lanolin fatty acid, hexyl laurate, reduced lanolin, jojoba wax, hard lanolin, POE (polyoxyethylene) lanolin alcohol ether, POE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol, and POE hydrogenated lanolin alcohol ether.

[0022] Examples of hydrocarbon oils include liquid paraffin, squalene, paraffin, squalane, petrolatum, and microcrystalline wax.

[0023] Examples of high-grade fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, 12-hydroxystearic acid, undecylenic acid, tallic acid, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

[0024] Examples of higher alcohols include linear alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, and cetostearyl alcohol; and branched alcohols such as monostearyl glycerol ether, 2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyldodecanol, isostearyl alcohol, and octyldodecanol.

[0025] Examples of synthetic ester oils include isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearylate, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, neopentyl glycol dicaprate, diisostearyl malate, glyceryl di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane triisostearate, and pentane tetra-2-ethylhexylate. Examples include slitol, glyceryl tri-2-ethylhexylate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glyceryl trimiristicate, glyceride tri-2-heptylundecanoate, castor oil fatty acid methyl ester, oleic acid oil, cetostearyl alcohol, 2-heptylundecyl palmitate, diisobutyl adipate, 2-octyldodecyl N-lauroyl-L-glutamate, di-2-heptylundecyl adipate, ethyl laurate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebatate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate, etc.

[0026] Examples of silicones include linear polysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane, and methylhydrogenpolysiloxane; alicyclic polysiloxanes such as decamethylpolysiloxane, dodecamethylpolysiloxane, and tetramethyltetrahydrogenpolysiloxane; and silicone resins and silicone rubbers that form a three-dimensional network structure.

[0027] Examples of anionic surfactants include: soap base, fatty acid soaps such as sodium laurate and sodium palmitate; higher alkyl sulfate esters such as sodium lauryl sulfate and potassium lauryl sulfate; alkyl ether sulfate esters such as POE lauryl sulfate triethanolamine and POE lauryl sulfate sodium; N-acyl sarcosinates such as sodium lauroyl sarcosinate; higher fatty acid amide sulfonates such as sodium N-myristoyl-N-methyl taurate, sodium coconut oil fatty acid methyl taulide, and sodium lauryl methyl taulide; phosphate esters such as sodium POE oleyl ether phosphate and POE stearyl ether phosphate; and sodium di-2-ethylhexyl sulfosuccinate, monolauroyl monoethanolamide polyoxyethylene sulfosuccinate sodium, and sodium lauryl polypropylene glycol sulfosuccinate sodium. Examples include sulfosuccinates; alkylbenzene sulfonates such as linear dodecylbenzenesulfonate sodium, linear dodecylbenzenesulfonate triethanolamine, and linear dodecylbenzenesulfonate; N-acyl glutamates such as N-lauroyl glutamate monosodium, N-stearoyl glutamate disodium, and N-myristoyl-L-glutamate monosodium; higher fatty acid ester sulfates such as hydrogenated coconut oil fatty acid glycerin sulfate sodium; sulfurized oils such as belladonna oil; POE alkyl ether carboxylic acids, POE alkyl allyl ether carboxylic acid salts, α-olefin sulfonates, higher fatty acid ester sulfonates, secondary alcohol sulfates, higher fatty acid alkylolamide sulfates, lauroyl monoethanolamide succinate sodium, N-palmitoyl aspartate ditriethanolamine, and sodium caseinate.

[0028] Examples of cationic surfactants include alkyltrimethylammonium salts such as stearyltrimethylammonium chloride and lauryltrimethylammonium chloride; alkylpyridinium salts such as distearyldimethylammonium chloride dialkyldimethylammonium salt, poly(N,N'-dimethyl-3,5-methylenepiperidinium) chloride and cetylpyridinium chloride; alkylquaternary ammonium salts, alkyldimethylbenzylammonium salts, alkylisoquinolinium salts, dialkylmolyphonium salts, POE alkylamines, alkylamine salts, polyamine fatty acid derivatives, amyl alcohol fatty acid derivatives, benzalkonium chloride, and benzethonium chloride.

[0029] Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants such as 2-undecyl-N,N,N-(hydroxyethylcarboxymethyl)-2-imidazoline sodium and 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt; and betaine-based surfactants such as 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkyl betaine, amide betaine, and sulfobetaine.

[0030] Examples of lipophilic nonionic surfactants include sorbitan fatty acid esters such as sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, sorbitan penta-2-ethylhexylate diglycerol sorbitan, and sorbitan tetra-2-ethylhexylate diglycerol sorbitan; glycerin polyglycerin fatty acids such as monocottonseed oil fatty acid glycerin, monoerucate glycerin, sesquioleate glycerin, monostearate glycerin, α,α'-oleate pyroglutamate glycerin, and monostearate glycerin malic acid; propylene glycol fatty acid esters such as propylene glycol monostearate; hydrogenated castor oil derivatives; and glycerin alkyl ethers.

[0031] Examples of hydrophilic nonionic surfactants include POE sorbitan fatty acid esters such as POE sorbitan monooleate, POE-sorbitan monostearate, POE-sorbitan monooleate, and POE-sorbitan tetraoleate; POE sorbitan fatty acid esters such as POE-sorbitan monolaurate, POE-sorbitan monooleate, POE-sorbitan pentaoleate, and POE-sorbitan monostearate; and POE-glycerin monostearate, POE-glycerin monoisostearate, and POE-glycerin. POE glycerin fatty acid esters such as lyisostearate; POE fatty acid esters such as POE monooleate, POE distearate, POE monodioleate, and ethylene glycol cystearate; POE alkyl ethers such as POE lauryl ether, POE oleyl ether, POE stearyl ether, POE behenyl ether, POE 2-octyldodecyl ether, and POE cholestanol ether; POE alkyl ethers such as POE octylphenyl ether, POE nonylphenyl ether, and POE dinonylphenyl ether. Nyl ethers; Pluraronic types such as Bluronic; POE-POP alkyl ethers such as POE-POP cetyl ether, POE-POP 2-decyltetradecyl ether, POE-POP monobutyl ether, POE-POP hydrogenated lanolin, POE-POP glycerin ether; Tetra-POE-tetraPOP ethylenediamine condensates such as Tetronic; POE castor oil, POE hydrogenated castor oil, POE hydrogenated castor oil monoisostearate, POE hydrogenated castor oil triisostearate, POE hydrogenated castor oil monopyroglutamic acid monoiso Examples include POE castor oil derivatives such as stearic acid diester and POE hydrogenated castor oil maleic acid; POE beeswax / lanolin derivatives such as POE sorbitan beeswax; alkanolamides such as coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, and fatty acid isopropanolamide; and POE propylene glycol fatty acid ester, POE alkylamine, POE fatty acid amide, sucrose fatty acid ester, POE nonylphenylformaldehyde condensate, alkylethoxydimethylamine oxide, and trioleyl phosphate.

[0032] Examples of humectants include polyethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, xylitol, sorbitol, maltitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, cholesteryl-12-hydroxystearate, ceramide, glucosylceramide, sodium lactate, bile salts, dl-pyrrolidone carboxylate, short-chain soluble collagen, diglycerin (EO)PO adduct, Rosa rugosa extract, Achillea millefolium extract, and Melilotus extract.

[0033] Examples of naturally occurring water-soluble polymer compounds include plant-derived polymers such as gum arabic, tragacanth gum, galactan, carob gum, karaya gum, carrageenan, pectin, agar, quince seed, algae colloid (cassia extract), starch (rice, corn, potato, wheat), and glycyrrhizic acid; microbial polymers such as xanthan gum, dextran, succinoglucan, and pullulan; and animal-derived polymers such as collagen, casein, albumin, and gelatin.

[0034] Examples of semi-synthetic water-soluble polymer compounds include starch-based polymer compounds such as carboxymethyl starch and methylhydroxypropyl starch; cellulose-based polymer compounds such as methylcellulose, nitrocellulose, ethylcellulose, methylhydroxypropylcellulose, hydroxyethylcellulose, sodium cellulose sulfate, hydroxypropylcellulose, sodium carboxymethylcellulose (CMC), crystalline cellulose, and cellulose powder; and alginate-based polymer compounds such as sodium alginate and propylene glycol alginate.

[0035] Examples of synthetic water-soluble polymer compounds include vinyl polymers such as polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, and carboxyvinyl polymer (e.g., "Carbopol®" manufactured by Lubrizol Advanced Materials); polyoxyethylene polymers such as polyethylene glycol 20,000, 4,000,000, and 600,000; polyoxyethylene polyoxypropylene copolymer polymers; acrylic polymers such as sodium polyacrylate, polyethyl acrylate, and polyacrylamide; polyethyleneimine, cationic polymers, and the like.

[0036] Examples of inorganic water-soluble polymer compounds include bentonite, magnesium aluminum silicate (e.g., "Beegum" manufactured by Build), laponite, hectorite, and anhydrous silicic acid.

[0037] Examples of thickening agents include gum arabic, carrageenan, karaya gum, tragacanth gum, carob gum, quince seed, casein, dextrin, gelatin, sodium pectinate, sodium araginate, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium polyacrylate, carboxyvinyl polymer, dialkyldimethylammonium sulfate cellulose, xanthan gum, aluminum magnesium silicate, and bentonite.

[0038] Examples of UV absorbers include benzoic acid-based UV absorbers such as para-aminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglycerol ester, N,N-dipropoxy PABA ethyl ester, N,N-diethoxy PABA ethyl ester, N,N-dimethyl PABA ethyl ester, N,N-dimethyl PABA butyl ester, and N,N-dimethyl PABA butyl ester; anthranilic acid-based UV absorbers such as homomenthyl-N-acetylanthranilate; amyl salicylate, menthyl salicylate, and homomenthyl salicylate. Salicylic acid-based UV absorbers such as octyl salicylate, phenyl salicylate, benzyl salicylate, and p-isopropanolphenyl salicylate; octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, methyl-2,4-diisopropyl cinnamate, propyl-p-methoxy cinnamate, isopropyl-p-methoxy cinnamate, isoamyl-p-methoxy cinnamate, octyl-p-methoxy Cinnamic acid-based UV absorbers such as cycinnamate (2-ethylhexyl-p-methoxycinnamate), 2-ethoxyethyl-p-methoxycinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate, glyceryl mono-2-ethylhexanoyl-diparamethoxycinnamate; 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'- Benzophenone-based UV absorbers such as dimethoxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenylbenzophenone, 2-ethylhexyl-4'-phenylbenzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, and 4-hydroxy-3-carboxybenzophenone;Examples include 3-(4'-methylbenzylidene)-d,1-camphor, 3-benzylidene-d,1-camphor, urocanic acid, ethyl urocanic acid, 2-phenyl-5-methylbenzoxazole, 2,2'-hydroxy-5-methylphenylbenzotriazole, 2-(2'-hydroxy-5'-t-octylphenyl)benzotriazole, 2-(2'-hydroxy-5'-methylphenylbenzotriazole), dibenzarazine, dianisioylmethane, 4-methoxy-4'-t-butyldibenzoylmethane, and 5-(3,3-dimethyl-2-norbornylidene)-3-pentan-2-one.

[0039] Examples of UV-blocking agents include titanium dioxide, talc, carmine, bentonite, kaolin, and zinc oxide.

[0040] Examples of preservatives include methylparaben, ethylparaben, propylparaben, phenoxyethanol, and sodium benzoate.

[0041] Examples of metal ion chelating agents include 1-hydroxyethane-1,1-diphosphonic acid, tetrasodium 1-hydroxyethane-1,1-diphosphonic acid, disodium edetate, trisodium edetate, tetrasodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, and edetate.

[0042] Examples of lower alcohols include methanol, ethanol, propanol, isopropanol, isobutyl alcohol, and t-butyl alcohol.

[0043] Examples of polyhydric alcohols include dihydric alcohols such as ethylene glycol, propylene glycol, trimethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, tetramethylene glycol, 2,3-butylene glycol, pentamethylene glycol, 2-butene-1,4-diol, hexylene glycol, and octylene glycol; trihydric alcohols such as glycerin, trimethylolpropane, and 1,2,6-hexanetriol; tetrahydric alcohols such as pentaerythritol; pentahydric alcohols such as xylitol; hexahydric alcohols such as sorbitol and mannitol; polyhydric alcohol polymers such as diethylene glycol, dipropylene glycol, triethylene glycol, polypropylene glycol, tetraethylene glycol, diglycerin, polyethylene glycol, triglycerin, tetraglycerin, and polyglycerin; ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, and ethylene Divalent alcohol alkyl ethers such as glycol mono-2-methylhexyl ether, ethylene glycol isoamyl ether, ethylene glycol benzyl ether, ethylene glycol isopropyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, and ethylene glycol dibutyl ether; divalent alcohol alkyl diethers such as diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol butyl ether, diethylene glycol methyl ethyl ether, triethylene glycol monomethyl ether, triethylene glycol monoethyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, propylene glycol isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, and dipropylene glycol butyl ether;Dihydric alcohol ether esters such as ethylene glycol monomethyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, ethylene glycol monophenyl ether acetate, ethylene glycol diazibate, ethylene glycol disuccinate, diethylene glycol monoethyl ether acetate, diethylene glycol monobutyl ether acetate, propylene glycol monomethyl ether acetate, propylene glycol monoethyl ether acetate, propylene glycol monopropyl ether acetate, and propylene glycol monophenyl ether acetate. Examples include: glycerin monoalkyl ethers such as xyl alcohol, cerakyl alcohol, and batyl alcohol; sugar alcohols such as sorbitol, maltitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, starch-derived sugars, maltose, xylitol, and starch-derived sugar-reduced alcohols; and glycerol, tetrahydrofurfuryl alcohol, POE tetrahydrofurfuryl alcohol, POP butyl ether, POP-POE butyl ether, tripolyoxypropylene glycerin ether, POP glycerin ether, POP glycerin ether phosphate, and POP-POE pentaneerythritol ether.

[0044] Examples of monosaccharides include trisaccharides such as D-glyceryl aldehyde and dihydroxyacetone; tetrasaccharides such as D-erythritol, D-erythritol, D-threose, and erythritol; pentoses such as L-arabinose, D-xylose, L-lyxose, D-arabinose, D-ribose, D-ribulose, D-xylulose, and L-xylulose; and D-glucose, D-talose, D-busicose, D-galactose, D-fructose, L-galactose, and L- Examples include hexoses such as mannose and D-tagatose; heptasaccharides such as aldoheptose and hepulose; octoses such as octulose; deoxy sugars such as 2-deoxy-D-ribose, 6-deoxy-L-galactose, and 6-deoxy-L-mannose; amino sugars such as D-glucosamine, D-galactosamine, sialic acid, aminouronic acid, and muramic acid; and uronic acids such as D-glucuronic acid, D-mannuronic acid, L-guluronic acid, D-galacturonic acid, and L-iduronic acid.

[0045] Examples of oligosaccharides include sucrose, gunthianose, umbelliferose, lactose, planteose, isolichnoses, α,α-trehalose, raffinose, licnoses, unbilicin, stachyose, and vervasocose.

[0046] Examples of polysaccharides include cellulose, quince seed, chondroitin sulfate, starch, galactan, dermyl sulfate, glycogen, gum arabic, heparan sulfate, hyaluronic acid, tragacanth gum, chondroitin, xanthan gum, mucoitin sulfate, guar gum, dextran, and carotenoid acid.

[0047] Examples of amino acids include neutral amino acids such as glycine, alanine, valine, leucine, isoleucine, serine, threonine, tryptophan, cystine, cysteine, methionine, proline, and hydroxyproline; acidic amino acids such as aspartic acid, glutamic acid, asparagine, and glutamine; and basic amino acids such as arginine, histidine, lysine, and hydroxylysine.

[0048] Examples of amino acid derivatives include sodium acyl sarcosinate (sodium lauroyl sarcosinate), acyl glutamate, sodium acyl β-alanine, glutathione, and pyrrolidone carboxylic acid.

[0049] Examples of organic amines include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, and 2-amino-2-methyl-1-propanol.

[0050] Examples of synthetic resin emulsions include acrylic resin emulsion, ethyl polyacrylate emulsion, acrylic resin liquid, polyacrylic alkyl ester emulsion, and polyvinyl acetate resin emulsion.

[0051] Examples of pH adjusters include buffering agents such as malic acid-sodium malate, lactate-sodium lactate, and citrate-sodium citrate.

[0052] Examples of vitamins include vitamin A oil, vitamin A derivatives such as retinol, vitamin B1 derivatives such as thiamine, vitamin B2 derivatives such as riboflavin, vitamin B6 derivatives such as pyridoxine hydrochloride, vitamin C derivatives such as L-ascorbic acid, L-ascorbic acid phosphate, L-ascorbic acid monopalmitate, L-ascorbic acid dipalmitate, and L-ascorbic acid-2-glucoside, pantothenic acids such as calcium pantothenate, vitamin D derivatives such as vitamin D2 and cholecalciferol; vitamin E derivatives such as α-tocopherol, tocopherol acetate, and DL-α-tocopherol nicotinate, pantothenic acid and its derivatives, and biotin.

[0053] Examples of antioxidants include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, and gallic acid esters. Examples of antioxidant auxiliary agents include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, kephalin, hexametaphosphorate, phytic acid, and ethylenediaminetetraacetic acid.

[0054] The dosage form of the topical skin preparation according to the embodiment is arbitrary, and a dosage form suitable for the target product can be obtained by conventional methods by combining one or more of the above-mentioned additives with the collagen production promoter, such as a solution system, solubilization system, emulsification system, oil-liquid system, gel system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, etc.

[0055] Furthermore, it is known that multiple steps, including tyrosinase-related processes and transport to the epidermis, are involved in the skin whitening effect, and the whitening effect can be strengthened by using a combination of various skin whitening compounds.

[0056] The topical skin preparation according to this embodiment preferably has a pH of 0.5 to 12, more preferably 1 to 10, 2 to 8, or 3 to 7, and particularly preferably 3.5 to 7. By setting the pH within this range, the collagen production promoting effect of the compound of formula (I) or its salt is more effectively exerted.

[0057] The collagen production promoter described above can also be used as a fragrance composition by mixing one or more commonly used fragrance components. "Commonly used fragrance components" here include various synthetic fragrances, natural essential oils, synthetic essential oils, citrus oils, and animal-derived fragrances. For example, a wide range of fragrance components can be used, as described in "Perfume and Flavor Chemicals (Aroma Chemicals) 1,2" (Steffen Arctender (1969)), "Synthetic Fragrances: Chemistry and Product Knowledge <Revised and Expanded Edition>" by Motoichi Indo, Chemical Daily Co., Ltd., March 22, 2005, revised and expanded edition), and "Collection of Well-Known and Conventional Technologies (Fragrances) Part I" (January 29, 1999, published by the Japan Patent Office). Representative examples of these include, for instance, α-pinene, limonene, cis-3-hexenol, phenylethyl alcohol, styraryl acetate, ammonium isovalerate, eugenol, rose oxide, linalool, benzaldehyde, muscone, Musk T (registered trademark, manufactured by Takasago International Corporation), Tesalon (registered trademark, Takasago International Corporation), and fragrances having a cooling effect such as menthol and derivatives having a menthane skeleton. By using these fragrances in combination with the collagen production promoter according to the embodiment, the fragrance quality and aroma profile of the blended fragrance can be improved.

[0058] The above-mentioned collagen production promoter may have not only a collagen production promoting effect, but also one or more of the following effects (a) to (g). (a) Dissolving ability for oils (b) Solubility for oils and fats (c) Chemical peeling ability (d) Ability to remove acne bacteria (e) Melanin production inhibitory ability (f) Increased mRNA expression of Type I collagen (g) Antioxidant effect

[0059] Furthermore, the fact that the compound represented by formula (I) or its salt contained in the above-mentioned collagen production promoter has the effects (a) to (e) is described in the examples described later and in the prior patent application (Japanese Patent Application No. 2024-175023) filed by the present applicant, and the contents of the said prior patent application are incorporated herein by reference.

[0060] By possessing the efficacy of (e) and the efficacy of (a) and / or (b), the above collagen production promoter has the effect of dissolving keratin plugs and excess sebum in addition to promoting collagen production, and can bring about a melanin production inhibitory effect deep within the skin, making it useful in improving rough skin and acne. By possessing the effects of (e) and (c), the above collagen production promoter has the effect of removing unnecessary keratin layers in addition to promoting collagen production, and can bring about a melanin production inhibitory effect deep within the skin, and is also useful in improving skin blemishes, dullness, fine wrinkles, and acne. Furthermore, by possessing the efficacy of (d), the above-mentioned collagen production promoter has the effect of eliminating acne-causing bacteria in addition to promoting collagen production, and is also useful in improving acne.

[0061] Here, the oils in (a) above refer to fatty acids that are liquid at room temperature, such as oleic acid, linoleic acid, and linolenic acid. The fats and oils in (b) above refer to fatty acids, fatty acid esters, or mixtures thereof that are solid at room temperature, such as palmitic acid, lauric acid, myristic acid, stearic acid, palmitic acid glyceride, lauric acid glyceride, myristic acid glyceride, and stearate glyceride.

[0062] The collagen production promoter described above is preferable if it possesses two or more of the effects described in (a) to (e) above, from the viewpoint of improving acne and promoting collagen production to the deeper layers of the skin. Furthermore, it is more preferable if it possesses three or more of the effects described in (a) to (e) above, from the viewpoint of improving rough skin and acne and promoting collagen production to the deeper layers of the skin. Furthermore, it is even more preferable if it possesses all of the effects, from the viewpoint of improving skin blemishes, dullness, fine lines, rough skin, and acne and promoting collagen production to the deeper layers of the skin. Furthermore, if the collagen production promoter described above also possesses one or more of the effects (f) and (g), it will help maintain skin elasticity and firmness, reduce reactive oxygen species that cause aging such as blemishes and wrinkles, and ultimately reduce skin aging. [Examples]

[0063] The present invention will be specifically described below with reference to examples, but the present invention is not limited in any way by these examples, and various changes and modifications may be made without departing from the scope of the present invention. In the formulations described below, unless otherwise specified, "%" means "weight percent," and composition ratios are expressed as weight ratios. Unless otherwise specified, the reagents used were those manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Methyl lactic acid was manufactured by Mitsubishi Gas Chemical Company, Inc.

[0064] <Example 1: Cytotoxicity Test> ·Cell culture conditions Normal human fibroblasts (NHDFs: manufactured by Kurabo Industries Ltd.) were used as collagen-producing cells, and Dulbecco's Modified Eagle Medium (DMEM: manufactured by Sigma-Aldrich) containing 5% FBS (Fetal bovine serum; FBS) was used as the cell culture medium, with 2.0 × 10⁶ cells placed in a 96-well plate. 4 Cells were seeded at a cell density of cells / well / 100μL and cultured for 24 hours at 37°C in the presence of 5% by volume carbon dioxide.

[0065] • Test sample For five test samples, methyllactic acid was adjusted to pH=6.5 by adding NaOH, and this adjusted methyllactic acid was added to 0.5% FBS-containing DMEM at concentrations of 2.5 mM, 5 mM, 10 mM, 20 mM, and 40 mM, respectively (mM represents mmol / l). As a control (Comparative Example 1), 0.5% FBS-containing DMEM without added methyllactic acid was used.

[0066] ·Cytotoxicity measurement conditions The culture medium was removed from the culture obtained under the cell culture conditions described above, and each test sample was added (100 μL / well) and cultured for 24 hours. After removing each test sample, 0.033% Neutral Red (NR)-containing DMEM was added (100 μL / well), and the culture was then incubated for 3 hours. To the cells after medium removal, a 30% MeOH solution containing 1 M (mol / l) HCl was added (100 μL / well), and the absorbance (measurement wavelength: 540 nm, reference wavelength: 650 nm) was measured.

[0067] The results are shown in Figure 1. In the figure, the cell viability (%) is the relative value (%) when the absorbance of the control medium only (methyllactic acid 0 mM) is set as 100% cell viability, since the absorbance is proportional to the number of viable cells in one sample (well). It is the average value of the values ​​measured for four samples for each of the five test samples. As shown in Figure 1, no cytotoxicity was observed when methyllactic acid was added (horizontal axis represents data for 2.5 mM, 5 mM, 10 mM, 20 mM, and 40 mM). Note that cytotoxicity is considered not to have occurred if the cell viability is 90% or higher, and cytotoxicity is considered to have occurred if the cell viability is less than 90%.

[0068] <Example 2: Collagen production promotion test> ·Cell culture conditions Cell cultures were prepared using the same method as in Example 1 above.

[0069] • Test sample For the ten test samples, methyl lactic acid or glycolic acid was adjusted to pH=6.5 by adding NaOH, and the adjusted methyl lactic acid or glycolic acid was added to 0.5% FBS-containing DMEM at concentrations of 2.5 mM, 5 mM, 10 mM, 20 mM, and 40 mM, respectively. As a control (Comparative Example 2), 0.5% FBS-containing DMEM without the addition of methyl lactic acid or glycolic acid was used.

[0070] • Measurement conditions for collagen production promotion effect The culture medium was removed from the culture obtained under the cell culture conditions described above, and each test sample was added (100 μL / well) and cultured for 24 hours. The culture medium was collected, and the amount of type I collagen in the culture supernatant was measured by ELISA (Enzyme-Linked Immuno Sorbent Assay) (measurement wavelength: 450 nm). After lysing the cells with 0.5% TritonX-100-containing phosphate-buffered saline (PBS(-)), the protein mass was quantified using the BCA protein assay kit (Thermo Fisher Scientific), and the amount of type I collagen per unit protein was calculated.

[0071] The results are shown in Figure 2. In Figure 2, "Control" (Comparative Example 2) is the negative control, and the culture medium used was one without the test sample added. Also, the Type I collagen (ng / μg protein) shown in Figure 2 is the amount of Type I collagen produced per unit protein, and the amount of Type I collagen increases if collagen production is promoted. The values ​​on the vertical axis of Figure 2 (Type I collagen and Protein) are the average values ​​of five samples measured for each of the 10 test samples. In Figure 2, "HBA-Na" is the test sample to which adjusted methyllactic acid was added, and "Sodium glycolate" is the test sample to which adjusted glycolic acid was added (the values ​​on the horizontal axis represent the respective concentrations).

[0072] As shown in Figure 2, when glycolic acid was added (labeled "Sodium Glycolate" in the figure), the collagen production-promoting effect increased with increasing glycolic acid concentration, but cytotoxicity was observed at glycolic acid concentrations of 20 mM or higher, resulting in a decrease in protein mass (value labeled "protein" in the figure). On the other hand, when methyllactic acid was added (labeled "HBA-Na" in the figure), the collagen production-promoting effect increased with increasing methyllactic acid concentration, but no decrease in protein mass due to cytotoxicity was observed even at methyllactic acid concentrations of 20 mM or higher.

[0073] <Example 2-2: Expression test of Type I collagen gene in dermal matrix components> ·Cell culture conditions Cell cultures were prepared using the same method as in Example 1 above.

[0074] • Test sample As test samples, methyllactic acid was adjusted to pH=6.5 by adding NaOH, and this adjusted methyllactic acid was added to 0.5% FBS-containing DMEM to concentrations of 10 mM, 20 mM, and 40 mM. As a control (Comparative Example 2-2), 0.5% FBS-containing DMEM without added methyllactic acid was used.

[0075] • Measurement conditions for Type I collagen gene expression The culture medium was replaced with the test sample (100 μL / well), and the cells were incubated for 24 hours. After removing the medium, RNA was extracted using Cells-to-Ctkit (Themo), and cDNA was synthesized by reverse transcription. Real-time PCR was performed using the obtained cDNA, and the relative mRNA expression level was calculated.

[0076] The results are shown in Figure 3. In Figure 3, "Control" is the negative control, and the culture medium used did not contain the test sample. Figure 3 shows the relative expression levels of Type I collagen mRNA. When methyllactic acid was added, a dose-dependent increase in Type I collagen mRNA expression was observed.

[0077] The mechanism of the collagen production-promoting effect in Example 2 was shown to be that methyllactic acid increased the expression of Type I collagen genes, thereby promoting collagen production in fibroblasts.

[0078] <Example 2-3: Antioxidant activity test> <Example 2-3-1: Effect of methyllactic acid on NAD+ / NADH levels in senescence-induced fibroblasts> ·Cell culture conditions Cell cultures were prepared using the same method as in Example 1 above.

[0079] • Test sample As test samples, methyllactic acid was adjusted to pH=6.5 by adding NaOH, and this adjusted methyllactic acid was added to 0.5% FBS-containing DMEM at concentrations of 10 mM, 20 mM, and 40 mM. As controls (Comparative Examples 2-3), 0.5% FBS-containing DMEM without added methyllactic acid was used.

[0080] • Induction of senescent cells and application of test samples The culture medium was replaced with 0.5% FBS-containing DMEM containing 200 μM hydrogen peroxide (100 μL / well), and the cells were treated for 1 hour to induce senescence. After washing the medium, it was replaced with the test sample (100 μL / well), and the cells were cultured for 24 hours before the test sample was applied. The above senescence induction treatment, washing, and test sample application were repeated a total of three times. After treatment, the cells were cultured for an additional 72 hours.

[0081] • Measurement conditions for antioxidant activity (NAD+ / NADH values) Cells were harvested, seeded in a 6-well plate, and NAD+ / NADH levels were measured. The NAD / NADH Assay Kit-WST (Dojin Chemical Research Institute) was used to measure NAD+ / NADH levels.

[0082] The results are shown in Figure 4. In Figure 4, "Control" represents the untreated control sample, "Normal" represents the results for the group that did not undergo aging induction, and "Senescence" represents the results for the group that underwent aging induction. Figure 4 shows the NAD+ / NADH values. In the Control group, a decrease in NAD+ / NADH was observed in the senescence group, which was repeatedly treated with hydrogen peroxide, compared to the Normal group, which was not repeatedly treated with hydrogen peroxide. Furthermore, it was found that the decrease in NAD+ / NADH values ​​was suppressed when methyl lactate was added. NAD+ contributes to the activation of sirtuin genes, and it is known that suppressing the decrease in NAD+ / NADH values ​​leads to the expression of antioxidant enzymes.

[0083] The antioxidant effect of methyllactic acid suggests that it activates fibroblasts and promotes collagen production.

[0084] <Example 2-3-2: Effect of methyllactic acid on intracellular ROS (reactive oxygen species) that increase due to aging induction> The cell culture conditions, test samples, senescent cell induction, and application of test samples were carried out using the same procedures as those used in the above-mentioned study on the effect of methyllactic acid on NAD+ / NADH levels.

[0085] • Measurement conditions for intracellular ROS Cells were harvested, seeded in a 96-well plate, and intracellular ROS levels were measured. DCFDA (2',7'-dichlorofluorescein diacetate) was used to detect intracellular ROS levels, and the intracellular ROS level per unit of cellular protein was calculated.

[0086] The results are shown in Figure 5. In Figure 5, "Control" represents the untreated control sample, "Normal" represents the results for the group that did not undergo aging induction, and "Senescence" represents the results for the group that underwent aging induction. Figure 5 shows intracellular ROS levels. In the control group, an increase in intracellular ROS levels was observed in the senescence group, which was repeatedly treated with hydrogen peroxide, compared to the normal group, which was not repeatedly treated with hydrogen peroxide. Furthermore, it was observed that the increase in intracellular ROS levels was suppressed when methyl lactate was added. It is known that suppressing the increase in intracellular ROS can inhibit oxidative stress on cells and prevent collagen breakdown due to oxidation.

[0087] The antioxidant properties of methyllactic acid suggest that it protects fibroblasts from reactive oxygen species and promotes collagen production.

[0088] <Example 3, Comparative Examples 3-5: Tests concerning efficacy a-d> (Soluble capacity for oils) Oleic acid was added to a 50% by weight aqueous solution of the organic acid listed in Table 1 and stirred at room temperature (23°C) for 24 hours. If the saturation solubility of oleic acid was 200 ppm or higher, it was evaluated as A; if it was less than 200 ppm, it was evaluated as B. (Soluble capacity for oils and fats) Palmitic acid was added to a 50% by weight aqueous solution of an organic acid and stirred at room temperature (23°C) for 24 hours. If the saturation solubility of palmitic acid was 20 ppm or higher, it was evaluated as A; if it was less than 20 ppm, it was evaluated as B.

[0089] (Chemical peeling ability) A 7% by weight aqueous solution of organic acid was applied to pig skin for 24 hours. If the thickness of the stratum corneum decreased by 10% or more, it was evaluated as A; if it decreased by less than 10%, it was evaluated as B. (Acne bacteria removal ability) 5 mL of a test solution prepared with the bacterial strain Cutibacterium acnes NBRC 107605 at a concentration of 10⁸ CFU / mL was mixed with 0.05 mL of a 7 wt% aqueous solution of organic acid. After 60 seconds, if the number of viable bacteria was less than 1%, it was evaluated as A; if it was 1% or more, it was evaluated as B.

[0090] [Table 1]

[0091] The above test results show that methyl lactic acid possesses not only the melanin production inhibitory effect described later, but also the ability to dissolve oils, oils, chemical peels, and remove acne bacteria.

[0092] <Example 4: Evaluation of melanin production inhibitory activity related to efficacy e> ·Cell culture conditions Mouse-derived cutaneous melanoma cells, B16 melanoma (JCRB0202, purchased from JCRB Cell Bank), were used as melanin-producing cells. The cell culture medium consisted of 500 mL of E-MEM medium mixed with 5 mL of 100 × penicillin streptomycin solution and 100 mL of inactivated fetal bovine serum (West Bio). For cell subculturing, cells were washed with phosphate buffer solution (GIBCO), detached from the container with 0.25% trypsin and EDTA (ethylenediaminetetraacetic acid), added to the culture medium, and then separated by centrifugation. The cell concentration was adjusted to 5-16 × 10⁶ to ensure stable cell culture. 4 Adjust to a cell / mL ratio and use a 10cm petri dish or plastic culture flask (175cm). 2 The cells were cultured at 37°C in the presence of 5% by volume of carbon dioxide.

[0093] For the assay medium, we used a mixture of 500 mL of D-MEM (phenol red-free, glutamic acid-free), 5 mL of ×100 penicillin streptomycin solution, 100 mL of inanimate fetal bovine serum (West Bio), and 5 mL of GlutaMax ×100 (GIBCO).

[0094] • Test sample For the test sample (methyllactic acid 100 μM), methyllactic acid was prepared by adding NaOH to adjust the pH to 6.5, and this was added to the assay medium to a concentration of 100 μM. [Table 2]

[0095] • Melanin production rate measurement conditions Cells were detached from the culture obtained under the cell culture conditions described above, and the cell concentration was 40 × 10 4 Cells and 1 mL of culture medium were each inoculated into 12-well containers to achieve a cell / mL ratio. After 1 day of incubation, the culture medium was removed and replaced with the test sample. After 1 day of incubation, the cells were washed with assay medium and lysed with 125 μL of 1 M NaOH. 100 μL of this lysed cell solution was placed in a 96-well container. The absorbance at 450 nm was measured using a plate reader, and the melanin concentration was calculated.

[0096] The results are shown in Figure 6. In Figure 6, "Culture medium only" is the negative control, and uses assay medium without the test sample added. "Kojic acid 1 mM" is the positive control, and uses assay medium with 1 mM kojic acid added, which is known to have a melanin production inhibitory effect. The melanin production rate (%) shown in Figure 6 is a relative value (%) with the melanin concentration of the negative control set to 100%, and is the average value of the measurements taken for 12 samples. As can be seen from Figure 6, the addition of methyllactic acid showed a melanin production inhibitory effect equivalent to that of kojic acid.

[0097] The following are examples of topical skin preparations. The methyllactic acid used in the following examples is the same as that used in Examples 1-4. Note that each of the following examples (1-8) can also be used for skin whitening. <Example of prescription 1> Anti-wrinkle or anti-sagging cleansing lotion The ingredients shown in Table 3 below were dissolved at room temperature while stirring to prepare an anti-wrinkle or anti-sagging wipe-off lotion. [Table 3]

[0098] <Example of prescription 2> Anti-wrinkle or anti-sagging lotion The ingredients shown in Table 4 below were dissolved at room temperature while stirring to prepare an anti-wrinkle or anti-sagging lotion. [Table 4]

[0099] <Example prescription 3> Anti-wrinkle or anti-sagging cream The ingredients shown in Table 5 below were dissolved at room temperature while stirring to prepare an anti-wrinkle or anti-sagging cream. [Table 5]

[0100] <Example of prescription 4> Anti-wrinkle or anti-sagging lotion The ingredients shown in Table 6 below were dissolved at room temperature while stirring to prepare an anti-wrinkle or anti-sagging lotion. [Table 6]

[0101] <Prescription Example 5> Anti-wrinkle or anti-sagging gel The ingredients shown in Table 7 below were dissolved at room temperature while stirring to prepare an anti-wrinkle or anti-sagging gel. [Table 7]

[0102] <Example of prescription 6> Anti-wrinkle or anti-sagging serum The ingredients shown in Table 8 below were dissolved at room temperature while stirring to prepare an anti-wrinkle or anti-sagging serum. [Table 8]

[0103] <Example Prescription 7> Anti-wrinkle or anti-sagging facial cleanser The ingredients shown in Table 9 below were dissolved at room temperature while stirring to prepare an anti-wrinkle or anti-sagging facial cleanser. [Table 9]

[0104] <Prescription Example 8> Anti-wrinkle or anti-sagging soap The ingredients shown in Table 10 below were dissolved in an 80°C water bath while stirring, and then cooled and solidified to prepare an anti-wrinkle or anti-sagging soap. [Table 10]

[0105] While several embodiments of the present invention have been described, these embodiments are presented as examples only and are not intended to limit the scope of the invention. These novel embodiments can be carried out in a variety of other forms, and various omissions, substitutions, and modifications can be made without departing from the spirit of the invention. These embodiments and their variations are included in the scope and spirit of the invention, as well as in the claims of the invention and its equivalents.

Claims

1. Collagen production promoters containing a compound represented by formula (I) or a salt thereof: 【Chemistry 1】 [In formula (I), R represents an alkyl group having 1 to 4 carbon atoms.]

2. The collagen production promoter according to claim 1, wherein R in formula (I) is a methyl group.

3. Furthermore, the collagen production promoter according to claim 1 has one or more of the following effects (a) to (g): (a) Solubility for oils (b) Solubility for oils and fats (c) Chemical peeling ability (d) Ability to remove acne bacteria (e) Melanin production inhibitory ability (f) Increased mRNA expression of Type I collagen (g) Antioxidant effect.

4. The collagen production promoter according to claim 1, comprising 20 mM or more of the compound represented by formula (I) or a salt thereof.

5. A topical skin preparation comprising a collagen production promoter according to any one of claims 1 to 4.

6. The topical skin preparation according to claim 5, wherein the compound represented by formula (I) or a salt thereof is contained in an amount of 0.001 to 50% by weight relative to the topical skin preparation.

7. The topical skin preparation according to claim 5, further comprising one or more additives selected from the group consisting of thickeners, pH adjusters, preservatives, and antioxidants.

8. The topical skin preparation according to claim 7, wherein each of the additives is contained in an amount of 0.01 to 20% by weight relative to the topical skin preparation.

9. The topical skin preparation according to claim 5, wherein the pH is 0.5 to 12.

10. The topical skin preparation according to claim 5, which is an anti-wrinkle or anti-sagging cosmetic.

11. The anti-wrinkle or anti-sagging cosmetic is selected from the group consisting of lotions, creams, emulsions, gels, serums, facial cleansers, soaps, ointments, masks, and foundations, as described in claim 10.

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