Melanogenesis inhibitor and external preparation for skin containing same

Abstract

One embodiment of the present invention provides a melanogenesis inhibitor containing a compound represented by formula (I) or a salt thereof: [In formula (I), R represents an alkyl group having 1-4 carbon atoms].

Description

Melanin production inhibitor and topical skin preparation containing same

[0001] The present invention relates to a melanin production inhibitor and an external skin preparation containing the same.

[0002] When skin is exposed to ultraviolet rays from sunlight or UV lamps, it loses its luster, texture, and moisture. Damage to the dermis, in particular, by UV rays can cause wrinkles and sagging, a condition known as photoaging. Reactive oxygen species generated by UV exposure and various factors released from skin cells as a result of these effects enhance tyrosinase activity in melanocytes. Melanin, which is involved in skin tone, is produced by the oxidation of tyrosine by tyrosinase in melanocytes. When tyrosinase is activated by UV rays, excessive melanin is produced, which is then passed on to epidermal cells, leading to a change in skin tone and darkening.

[0003] Therefore, it is known that inhibiting melanin production is effective in achieving a whitening effect. Known active ingredients that inhibit melanin production include ascorbic acid, kojic acid, arbutin, ellagic acid, 4-alkylresorcinols or their derivatives, and various plant extracts. It is also known that the use of a compound consisting of an ester of menthol and a long-chain unsaturated fatty acid having 18 or more carbon atoms in combination with an inhibitor of a signal transmitter produced by keratinocytes, an antioxidant, an anti-inflammatory agent, a polymer compound, and a polyhydric alcohol exhibits a synergistic effect to inhibit melanin production (see, for example, Patent Document 1). Furthermore, it is also known that cedrol, a component of sandalwood oil, exhibits an inhibitory effect on melanin production (see, for example, Patent Document 2), and nerolidol, a component of cabreuva oil, exhibits an inhibitory effect on melanin production (see, for example, Patent Document 3).

[0004] On the other hand, vetiver extract is known to have a melanin production promoting effect (for example, Patent Document 4). As such, various components involved in melanin production are known, but in recent years, the harmful effects of ultraviolet rays have become widely recognized, and melanin production inhibitors have been attracting increasing attention.

[0005] JP 2007-161591, JP 10-36246, JP 6-72855, JP 2011-157317

[0006] An object of the present invention is to provide a melanin production inhibitor and an external skin preparation containing the same.

[0007] The present inventors have conducted extensive research to solve the above problems and have found that a compound having a specific structure or a salt thereof has a melanin production inhibitory effect, thereby completing the present invention. The present invention is, for example, as follows: [1] A melanin production inhibitor comprising a compound represented by formula (I) or a salt thereof: [In formula (I), R represents an alkyl group having 1 to 4 carbon atoms]. [2] The melanin production inhibitor according to [1], wherein R in formula (I) is a methyl group. [3] The melanin production inhibitor according to [1] or [2], further having any one or more of the following effects (a) to (d): (a) ability to dissolve oils (b) ability to dissolve oils and fats (c) chemical peeling ability (d) ability to remove acne bacteria. [4] A topical skin preparation comprising the melanin production inhibitor according to any of [1] to [3]. [5] The topical skin preparation according to [4], wherein the compound represented by formula (I) or its salt is contained in an amount of 0.001 to 50 wt % relative to the amount of the topical skin preparation. [6] The topical skin preparation according to [4] or [5], further comprising one or more additives selected from the group consisting of thickeners, pH adjusters, preservatives, and antioxidants. [7] The topical skin preparation according to [6], wherein the additives are each contained in an amount of 0.01 to 20% by weight relative to the amount of the topical skin preparation. [8] The topical skin preparation according to any one of [4] to [7], wherein the pH is 0.5 to 12. [9] The topical skin preparation according to any one of [4] to [8], which is a whitening cosmetic.

[10] The topical skin preparation according to [9], wherein the whitening cosmetic is selected from the group consisting of lotion, cream, emulsion, gel, serum, facial cleanser, soap, ointment, pack, and foundation.

[0008] According to the present invention, it is possible to provide a melanin production inhibitor and an external skin preparation containing the same.

[0009] 1 is a diagram showing the results of Example 1. 2 is a diagram showing the results of Example 2. 3 is a diagram showing the results of Example 3. 4 is a diagram showing the results of Example 4. 5 is a diagram showing the results of Example 5.

[0010]

[0023] According to one embodiment of the present invention, there is provided a melanin production inhibitor comprising a compound represented by the following formula (I) or a salt thereof: [In formula (I), R represents an alkyl group having 1 to 4 carbon atoms].

[0011] The alkyl group having 1 to 4 carbon atoms may be linear or branched, and examples thereof include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and t-butyl. R is preferably methyl, ethyl, or isopropyl, more preferably methyl or ethyl, and particularly preferably methyl. When R is methyl, the compound of formula (I) is 2-hydroxyisobutyric acid, which will hereinafter also be referred to as "methyl lactic acid." Salts of the compound of formula (I) are not limited, and pharmaceutically acceptable salts can be used. Examples of such salts include sodium salts, potassium salts, magnesium salts, and calcium salts. Of these, sodium salts and potassium salts are preferred.

[0012] The melanin production inhibitor according to the embodiment can effectively inhibit melanin production. Furthermore, topical skin preparations containing the melanin production inhibitor are stable, highly safe, and have excellent whitening effects. The reason for this effect is unclear, but is presumed to be as follows. Melanin is biosynthesized in melanosomes, which are membrane organelles within pigment cells. It is presumed that melanin production can be inhibited by controlling the expression and activity of tyrosinase, which is thought to be the rate-limiting enzyme in this biosynthesis, with the compound of formula (I). It is presumed that controlling the expression and activity of tyrosinase suppresses the reaction that converts tyrosine to dopaquinone and dopa, thereby inhibiting melanin production.

[0013] As shown in the examples below, the compound of formula (1) inhibits tyrosinase biosynthesis and tyrosinase protein expression, and further inhibits the expression of melanin synthesis-related factor mRNA. Thus, according to one embodiment, a tyrosinase biosynthesis inhibitor is provided, comprising the compound represented by formula (1) or a salt thereof. According to another embodiment, a tyrosinase protein expression inhibitor is provided, comprising the compound represented by formula (1) or a salt thereof. According to a further embodiment, a melanin synthesis-related factor mRNA expression inhibitor is provided, comprising the compound represented by formula (1) or a salt thereof.

[0014] The melanin production inhibitor according to the embodiment can be used in combination with other known melanin production inhibitors (e.g., pantetheine-s-sulfonic acid, isoferulic acid, ascorbic acid and derivatives thereof, hydroquinone and derivatives thereof, arbutin, kojic acid, linoleic acid (ester), ellagic acid, glycyrrhizic acid, lactic acid (ester) 4-alkylresorcinol, licorice extract, placenta extract, etc.). When multiple types of melanin production inhibitors are used in combination, they may be used simultaneously, sequentially, or separately. As described below, multiple types of melanin production inhibitors may be blended in a single topical skin preparation.

[0015] [2] External Skin Preparations According to another embodiment of the present invention, an external skin preparation is provided that contains the melanin production inhibitor described above. The compound represented by formula (I) or its salt is contained in an amount of, for example, 0.001 to 50 wt %, 0.001 to 5 wt %, or 0.01 to 0.1 wt % relative to the external skin preparation. By containing the compound of formula (I) or its salt in such an amount, a good melanin production inhibitory effect can be obtained. The content of the compound of formula (I) or its salt can be appropriately determined depending on the type and intended use of the external skin preparation.

[0016] By utilizing the melanin production inhibitory effect, the above-mentioned topical skin preparation can be used as a whitening cosmetic. Whitening cosmetic products are not particularly limited as long as they are applied to the skin, and examples include lotions, creams, emulsions, gels, beauty serums, facial cleansers, soaps, ointments, packs, foundations, etc. Such whitening cosmetic products can be produced according to commonly used formulation methods.

[0017] In addition to the melanin production inhibitor according to the embodiment, the topical skin preparation may contain additives commonly used in cosmetics, pharmaceuticals, etc. 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, moisturizers, water-soluble polymeric compounds, thickeners, film-forming agents, UV absorbers, UV screeners, preservatives, sequestering agents, lower alcohols, polyhydric alcohols, sugars, amino acid derivatives, organic amines, synthetic resin emulsions, pH adjusters, skin nutrients, vitamins, antioxidants, antioxidant aids, fragrances, and water. These additives can be selected as needed and appropriately incorporated. 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.

[0018] Furthermore, other medicinal and physiologically active ingredients, such as vitamins, skin activators, blood circulation promoters, resident flora control agents, active oxygen scavengers, anti-inflammatory agents, other whitening agents, and bactericides, can be appropriately blended as needed. The additives described above may be used alone or in combination. The amount of additive used is not particularly limited; for example, each additive may be added in an amount of 0.01 to 20 wt %, 0.01 to 5 wt %, or 0.01 to 1 wt % (per additive) relative to the topical skin preparation. Furthermore, the additives are preferably added in a total amount of 0.1 to 50 wt %, 0.1 to 20 wt %, or 0.1 to 5 wt % relative to the topical skin preparation. By including the additives in such amounts, the effects of the additives can be fully exerted without interfering with the effects of the compound of formula (I) or its salt, which is the active ingredient.

[0019] Specific examples of the additives are listed below. Examples of powder components include talc, kaolin, mica, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (calcined gypsum), calcium phosphate, hydroxyapatite, ceramic powder, metal soap (zinc myristate, calcium palmitate, aluminum stearate), polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, styrene-acrylic acid copolymer resin powder, organic powder such as cellulose powder, 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, and the like. inorganic green pigments such as talc; 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, and Red 405 Organic pigments such as Red No. 3, Red No. 104, Red No. 106, Red No. 227, Red No. 230, Red No. 401, Red No. 505, Orange No. 205, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203, Green No. 3, and Blue No. 1; organic pigments such as zirconium, barium, or aluminum lake; and natural pigments such as chlorophyll and β-carotene. However, the powder component is not limited to the above components as long as it is a powder that can be used in general cosmetics.

[0020] Examples of liquid oils and fats 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, germ oil, triglycerin, glycerin trioctanoate, and glycerin triisopalmitate.

[0021] Examples of solid fats and oils include cacao butter, coconut oil, horse fat, hardened coconut oil, palm oil, beef tallow, mutton tallow, hardened beef tallow, palm kernel oil, lard, beef bone fat, Japan wax kernel oil, hardened oil, beef trotter fat, Japan wax, and hardened castor oil.

[0022] Examples of waxes include beeswax, candelilla wax, cotton wax, rice bran wax, carnauba wax, bayberry wax, Ibota wax, spermaceti wax, lanolin, lanolin acetate, liquid lanolin, lanolin fatty acid isopropyl, 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.

[0023] Examples of hydrocarbon oils include liquid paraffin, squalene, paraffin, squalane, petrolatum, and microcrystalline wax.

[0024] Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, 12-hydroxystearic acid, undecylenic acid, tall acid, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

[0025] Examples of higher alcohols include straight-chain alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, and cetostearyl alcohol; and branched-chain alcohols such as monostearyl glycerin ether, 2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyldodecanol, isostearyl alcohol, and octyldodecanol.

[0026] 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-hydroxystearate, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid esters, neopentyl glycol dicaprate, diisostearyl malate, glycerin di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane triisostearate, pentanetrile tetra-2-ethylhexylate, Examples of suitable glyceryl tri-2-ethylhexanoate include thritol, glycerin tri-2-ethylhexanoate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glycerin trimyristate, tri-2-heptylundecanoic acid glyceride, castor oil fatty acid methyl ester, oleic acid oil, cetostearyl alcohol, 2-heptylundecyl palmitate, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, amyl acetate, and triethyl citrate.

[0027] Examples of silicones include chain 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.

[0028] Examples of anionic surfactants include fatty acid soaps such as soap bases, sodium laurate, and sodium palmitate; higher alkyl sulfates such as sodium lauryl sulfate and potassium lauryl sulfate; alkyl ether sulfates such as POE triethanolamine lauryl sulfate and sodium POE lauryl sulfate; 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 tauride, and sodium lauryl methyl tauride; phosphate salts such as sodium POE oleyl ether phosphate and POE stearyl ether phosphate; and sulfonates such as sodium di-2-ethylhexyl sulfosuccinate, sodium monolauroyl monoethanolamide polyoxyethylene sulfosuccinate, and sodium lauryl polypropylene glycol sulfosuccinate. alkylbenzenesulfonates such as linear sodium dodecylbenzenesulfonate, linear dodecylbenzenesulfonate triethanolamine, and linear dodecylbenzenesulfonic acid; N-acylglutamates such as monosodium N-lauroylglutamate, disodium N-stearoylglutamate, and monosodium N-myristoyl-L-glutamate; higher fatty acid ester sulfates such as hydrogenated coconut oil fatty acid glycerin sodium sulfate; sulfated oils such as turmeric oil; POE alkyl ether carboxylic acids, POE alkyl allyl ether carboxylates, α-olefin sulfonates, higher fatty acid ester sulfonates, secondary alcohol sulfates, higher fatty acid alkylolamide sulfates, sodium lauroylmonoethanolamide succinate, N-palmitoyl aspartic acid ditriethanolamine, and sodium caseinate.

[0029] 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; alkyl quaternary ammonium salts, alkyldimethylbenzylammonium salts, alkylisoquinolinium salts, dialkylmorphonium salts, POE alkylamines, alkylamine salts, polyamine fatty acid derivatives, amyl alcohol fatty acid derivatives, benzalkonium chloride, and benzethonium chloride.

[0030] 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, amido betaine, and sulfobetaine.

[0031] 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, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate; glycerin polyglycerin fatty acids such as glycerin monocottonseed oil fatty acid, glycerin monoerucate, glycerin sesquioleate, glycerin monostearate, α,α'-oleic acid pyroglutamate, and glycerin monostearate malate; propylene glycol fatty acid esters such as propylene glycol monostearate; hydrogenated castor oil derivatives; and glycerin alkyl ethers.

[0032] 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-sorbit monostearate; POE glycerin monostearate, POE-glycerin monoisostearate, and POE-glycerin monoisostearate; POE glycerin fatty acid esters such as POE monooleate, POE distearate, POE monodioleate, ethylene glycol cystearate, etc.; POE fatty acid esters such as POE lauryl ether, POE oleyl ether, POE stearyl ether, POE behenyl ether, POE 2-octyldodecyl ether, POE cholestanol ether, etc.; POE alkyl ethers such as POE octylphenyl ether, POE nonylphenyl ether, POE dinonylphenyl ether, etc. phenyl ethers; Pluronic types such as Pluronic; POE-POP alkyl ethers such as POE-POP cetyl ether, POE-POP 2-decyltetradecyl ether, POE-POP monobutyl ether, POE-POP hydrogenated lanolin, and POE-POP glycerin ether; tetraPOE-tetraPOP ethylenediamine condensates such as Tetronic; POE castor oil, POE hydrogenated castor oil, POE hydrogenated castor oil monoisostearate, POE hydrogenated castor oil triisostearate, and POE hydrogenated castor oil monopyroglutamic acid monoisostearate. Examples of suitable POE hydrogenated castor oil derivatives include stearic acid diesters and POE hydrogenated castor oil maleic acid; POE beeswax / lanolin derivatives such as POE sorbitol beeswax; alkanolamides such as coconut oil fatty acid diethanolamide, lauric acid monoethanolamide, and fatty acid isopropanolamide; POE propylene glycol fatty acid esters, POE alkylamines, POE fatty acid amides, sucrose fatty acid esters, POE nonylphenyl formaldehyde condensates, alkylethoxydimethylamine oxide, and trioleyl phosphate.

[0033] Examples of moisturizing agents 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 robur extract, yarrow extract, melilot extract, and the like.

[0034] Examples of natural water-soluble polymer compounds include plant-based polymer compounds such as gum arabic, tragacanth gum, galactan, carob gum, karaya gum, carrageenan, pectin, agar, quince seed (marmelo), algae colloid (cassow extract), starch (rice, corn, potato, wheat), and glycyrrhizic acid; microbial-based polymer compounds such as xanthan gum, dextran, succinoglucan, and pullulan; and animal-based polymer compounds such as collagen, casein, albumin, and gelatin.

[0035] 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 methyl cellulose, nitrocellulose, ethyl cellulose, methylhydroxypropyl cellulose, hydroxyethyl cellulose, sodium cellulose sulfate, hydroxypropyl cellulose, sodium carboxymethyl cellulose (CMC), crystalline cellulose, and cellulose powder; and alginic acid-based polymer compounds such as sodium alginate and propylene glycol alginate.

[0036] Examples of synthetic water-soluble polymer compounds include vinyl polymer compounds such as polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, and carboxyvinyl polymers (e.g., Carbopol (registered trademark) manufactured by Lubrizol Advanced Materials); polyoxyethylene polymer compounds such as polyethylene glycol 20,000, 4,000,000, and 600,000; polyoxyethylene-polyoxypropylene copolymer polymer compounds; acrylic polymer compounds such as sodium polyacrylate, polyethyl acrylate, and polyacrylamide; polyethyleneimine, and cationic polymers.

[0037] Examples of inorganic water-soluble polymer compounds include bentonite, silicate A1Mg (for example, "Beegum" manufactured by Build), laponite, hectorite, and silicic anhydride.

[0038] Examples of thickeners include gum arabic, carrageenan, karaya gum, tragacanth gum, carob gum, quince seeds, casein, dextrin, gelatin, sodium pectinate, sodium alginate, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium polyacrylate, carboxyvinyl polymer, dialkyldimethylammonium cellulose sulfate, xanthan gum, aluminum magnesium silicate, and bentonite.

[0039] Examples of the ultraviolet absorber include benzoic acid-based ultraviolet absorbers such as para-aminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglycerin 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 ethyl ester; anthranilic acid-based ultraviolet absorbers such as homomenthyl-N-acetylanthranilate; amyl salicylate, menthyl salicylate, and homomenthyl salicylate; salicylic acid-based ultraviolet absorbers such as octyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, and p-isopropanol phenyl salicylate; octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, methyl-2,4-diisopropyl cinnamate, propyl-p-methoxycinnamate, isopropyl-p-methoxycinnamate, isoamyl-p-methoxycinnamate, octyl-p-methoxycinnamate, Cinnamic acid-based ultraviolet absorbers such as cyclohexyl cinnamate (2-ethylhexyl-p-methoxycinnamate), 2-ethoxyethyl-p-methoxycinnamate, cyclohexyl-p-methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate, and glyceryl mono-2-ethylhexanoyl-di-para-methoxycinnamate; 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'- benzophenone-based ultraviolet 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'-phenyl-benzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, and 4-hydroxy-3-carboxybenzophenone;3-(4'-methylbenzylidene)-d,1-camphor, 3-benzylidene-d,1-camphor, urocanic acid, urocanic acid ethyl ester, 2-phenyl-5-methylbenzoxazole, 2,2'-hydroxy-5-methylphenylbenzotriazole, 2-(2'-hydroxy-5'-t-octylphenyl)benzotriazole, 2-(2'-hydroxy-5'-methylphenylbenzotriazole, dibenzalazine, dianisoylmethane, 4-methoxy-4'-t-butyldibenzoylmethane, 5-(3,3-dimethyl-2-norbornylidene)-3-pentan-2-one, and the like;

[0040] Examples of ultraviolet blocking agents include titanium oxide, talc, carmine, bentonite, kaolin, zinc oxide, etc. Examples of preservatives include methylparaben, ethylparaben, propylparaben, phenoxyethanol, sodium benzoate, etc.

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

[0042] Examples of the lower alcohol 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 glycol monomethyl ether. Dihydric 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; dihydric 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 diadipate, 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. glycerin monoalkyl ethers such as xyl alcohol, selachyl alcohol, and batyl alcohol; sugar alcohols such as sorbitol, maltitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, starch-decomposed sugars, maltose, xylitose, and starch-decomposed sugar-reduced alcohols; glysolid, 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 trioses such as D-glyceryl aldehyde and dihydroxyacetone; tetraoses such as D-erythrose, D-erythrulose, 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 pentoses such as D-glucose, D-talose, D-busicose, D-galactose, D-fructose, L-galactose and L- Examples include hexoses such as mannose and D-tagatose; heptoses such as aldoheptose and heprose; octooses such as octulose; deoxysugars such as 2-deoxy-D-ribose, 6-deoxy-L-galactose, and 6-deoxy-L-mannose; aminosugars 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, isolychnoses, α,α-trehalose, raffinose, lychnoses, umbilicin, stachyose, verbascoses, and the like.

[0046] Examples of polysaccharides include cellulose, quince seed, chondroitin sulfate, starch, galactan, dimethicone sulfate, glycogen, gum arabic, heparan sulfate, hyaluronic acid, tragacanth gum, chondroitin, xanthan gum, mucoitin sulfate, guar gum, dextran, and caronic 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 sarcosine (sodium lauroyl sarcosine), 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, polyethyl acrylate emulsion, acrylic resin liquid, polyacrylic alkyl ester emulsion, polyvinyl acetate resin emulsion, etc. Examples of pH adjusters include buffers such as malic acid-sodium malate, lactic acid-sodium lactate, and citric acid-sodium citrate.

[0051] Examples of vitamins include vitamin A oil, vitamin A such as retinol, vitamin B1 such as thiamine, vitamin B2 such as riboflavin, vitamin B6 such as pyridoxine hydrochloride, vitamin C 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 D2, and vitamin D such as cholecalciferol; vitamin E such as α-tocopherol, tocopherol acetate, and DL-α-tocopherol nicotinate, pantothenic acid and derivatives thereof, and biotin.

[0052] Examples of antioxidants include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, gallic acid esters, etc. Examples of antioxidant aids include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, cephalin, hexametaphosphate, phytic acid, ethylenediaminetetraacetic acid, etc.

[0053] The topical skin preparation according to the embodiment may be in any dosage form, and may be in a solution system, solubilized system, emulsion system, oil liquid system, gel system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, or the like, by compounding one or more of the above-mentioned additives with the above-mentioned melanin production inhibitor, and a dosage form appropriate for the desired product can be prepared in a conventional manner.

[0054] It is known that the whitening effect involves multiple steps, such as tyrosinase-related activities and transport to the epidermis, and the whitening effect can be strengthened by using a combination of various whitening compounds, including the representative compounds with whitening activity described in the background art.

[0055] The pH of the topical skin preparation according to the embodiment is preferably 0.5 to 12, more preferably 3 to 7, and particularly preferably 3.5 to 7. By adjusting the pH to within this range, the melanin production inhibitory effect of the compound of formula (I) or a salt thereof can be more effectively exerted. Furthermore, melanin production can be inhibited without killing resident bacteria in the skin, including melanoma cells.

[0056] The melanin production inhibitor according to the embodiment can also be used to prepare a fragrance composition by mixing one or more commonly used fragrance ingredients. Examples of "commonly used fragrance ingredients" include various synthetic fragrances, natural essential oils, synthetic essential oils, citrus oils, and animal-derived fragrances. For example, a wide variety of fragrance ingredients can be used, such as those described in "Perfume and Flavor Chemicals (Aroma Chemicals) 1, 2" (Steffen Arctender, 1969), "Synthetic Fragrances: Chemistry and Product Knowledge (Revised and Expanded Edition)" by Genichi Indo, published by The Chemical Daily on March 22, 2005, and "Collection of Well-Known and Commonly Used Techniques (Fragrances) Part I" (published by the Japan Patent Office on January 29, 1999). Representative examples of such fragrances include α-pinene, limonene, cis-3-hexenol, phenylethyl alcohol, styrallyl acetate, ammonium isovalerate, eugenol, rose oxide, linalool, benzaldehyde, muscone, Musk T (registered trademark, manufactured by Takasago International Corporation), Tesalon (registered trademark, manufactured by Takasago International Corporation), and fragrances having a cooling effect such as derivatives having a menthol or menthane skeleton. By using these fragrances in combination with the melanin production inhibitor according to the embodiment, it is possible to improve the fragrance quality and fragrance tone of the blended fragrance.

[0057] The melanin production inhibitor according to the embodiment not only has the melanin production inhibitory effect as described above, but may also have one or more of the following effects (a) to (d): (a) ability to dissolve oils (b) ability to dissolve oils and fats (c) chemical peeling ability (d) ability to remove acne bacteria

[0058] By combining the effects of (a) and / or (b), the melanin production inhibitor according to the embodiment has the effect of dissolving keratin plugs and excess sebum, can exert a melanin production inhibitory effect deep into the skin, and is also useful in improving rough skin and acne. By combining the effect of (c), the melanin production inhibitor according to the embodiment has the effect of removing unnecessary stratum corneum, can exert a melanin production inhibitory effect deep into the skin, and is also useful in improving skin blemishes, dullness, fine wrinkles, and acne. By combining the effect of (d), the melanin production inhibitor according to the embodiment has the effect of eliminating Propionibacterium acnes, which causes acne, and is also useful in improving acne. Here, "oil" refers to fatty acids that are liquid at room temperature, such as oleic acid, linoleic acid, and linolenic acid. The term "oil and fat components" refers to fatty acids, fatty acid esters or mixtures thereof that are solid at room temperature, and examples thereof include palmitic acid, lauric acid, myristic acid, stearic acid, palmitic acid glyceride, lauric acid glyceride, myristic acid glyceride, and stearic acid glyceride.

[0059] The melanin production inhibitor according to the embodiment preferably has two or more of the effects (a) to (d) above, from the viewpoint of improving acne and providing a melanin-inhibiting effect deep into the skin. Furthermore, it is more preferable that the melanin production inhibitor has three or more of the effects, from the viewpoint of improving rough skin and acne and providing a melanin-inhibiting effect deep into the skin. It is even more preferable that the melanin production inhibitor has all of the effects, from the viewpoint of improving blemishes, dullness, fine wrinkles, rough skin, and acne, and providing a melanin-inhibiting effect deep into the skin.

[0060] The present invention will be specifically described below using examples, but the present invention is not limited thereto in any way, 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 "% by weight" and composition ratios represent weight ratios. Unless otherwise specified, reagents used were manufactured by Fujifilm Wako Pure Chemical Industries. Methyl lactate was manufactured by Mitsubishi Gas Chemical.

[0061] Example 1: Evaluation of melanin production inhibitory activity Cell culture conditions Mouse-derived skin melanoma cells B16 melanoma (JCRB0202, purchased from JCRB Cell Bank) were used as melanin-producing cells. The cell culture medium was prepared by mixing 5 mL of 100x penicillin-streptomycin solution and 100 mL of heat-inactivated fetal bovine serum (West Bio) with 500 mL of E-MEM medium. For cell subculture, the cells were washed with phosphate buffer solution (GIBCO), detached from the vessel with 0.25% trypsin and EDTA (ethylenediaminetetraacetic acid), added to the culture medium, and then separated by centrifugation. The cell concentration was adjusted to 5-16x10 to ensure stable cell culture. ４ The concentration was adjusted to 100 cells / mL, and the culture medium was placed in a 10 cm Petri dish or a plastic culture flask (175 cm ２ ) and cultured at 37°C in the presence of 5% carbon dioxide.

[0062] The assay medium used was a mixture of 500 mL of D-MEM (phenol red-free, glutamic acid-free), 5 mL of x100 penicillin-streptomycin solution, 100 mL of heat-inactivated fetal bovine serum (West Bio), and 5 mL of GlutaMax x100 (GIBCO). Test sample The test sample (100 μM methyl lactate) was prepared by adding NaOH to methyl lactate to adjust the pH to 6.5, and added to the assay medium to a concentration of 100 μM methyl lactate.

[0063] Melanin production rate measurement conditions: Cells were detached from the culture obtained under the above-mentioned cell culture conditions, and the cell concentration was 40 × 10 ４ Cells and 1 mL of medium were planted in a 12-well container so that the cell density was 1 / mL. After culturing for one day, the medium was removed and replaced with the test sample. After culturing for one day, the cells were washed with assay medium, and 125 μL of 1 M NaOH was added to lyse the cells. 100 μL of the 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.

[0064] The results are shown in Figure 1. In Figure 1, "medium only" is a negative control, in which an assay medium without the addition of a test sample was used. "Kojic acid 1 mM" is a positive control, in which an assay medium with 1 mM kojic acid, which is known to have melanin production inhibitory effects, was used. The melanin production rate (%) shown in Figure 1 is a relative value (%) when the melanin concentration in the negative control is taken as 100%, and is the average value of the values ​​measured for each of the 12 samples. As can be seen from Figure 1, the addition of methyl lactic acid showed the same melanin production inhibitory effect as the addition of kojic acid.

[0065] Example 2: Cytotoxicity test Cell culture conditions Cell culture was carried out in the same manner as in Example 1. Test sample Test samples were prepared in the same manner as in Example 1.

[0066] Cytotoxicity Measurement Conditions Cells were detached from the culture obtained under the cell culture conditions shown in Example 1, and the cells were collected at a cell concentration of 5 × 10 ４ Cells and 0.1 mL of medium were planted in a 96-well container so that the cell density was 0.1 mL / mL. After culturing for one day, the medium was removed and replaced with the test sample. After culturing for another day, the wells were washed with assay medium, and 0.1 mL of a 1:9 mixture of Cell Counting Kit 8 and medium was added. After allowing the wells to stand for 30 minutes at 37°C in the presence of 5% carbon dioxide, the absorbance at 450 nm was measured using a plate reader, and the cell count was calculated.

[0067] The results are shown in Figure 2. The cell counts (%) are relative values ​​(%) when the cell count in the negative control (medium only) was set at 100%, and are the average values ​​measured for each of 16 samples. As can be seen from Figure 2, no cytotoxicity was observed when methyl lactic acid was added.

[0068] Example 3: Tyrosinase biosynthesis inhibitory effect test Cell culture conditions Normal human melanocytes (Kurabo Industries, Ltd.) were used as melanin-producing cells. Dermalife (Kurabo Industries, Ltd.) was used as the cell culture medium, and the cell concentration was 3 × 10 ４The cells were adjusted to 100 cells / mL and cultured in a 96-well plate at 37° C. in the presence of 5% carbon dioxide for 24 hours.

[0069] Test sample: Methyl lactic acid was adjusted to pH 6.5 by adding NaOH to the test sample, and methyl lactic acid was added to Dermalife to concentrations of 2.5, 5, 10, 20, and 40 mM. Dermalife without methyl lactic acid was used as a control.

[0070] Measurement conditions for tyrosinase biosynthesis inhibitory activity: The medium was removed from the culture obtained under the above-mentioned cell culture conditions and replaced with the test sample. After one day of culture, the medium was removed, and 0.5% Triton X-100-containing phosphate buffer was added to 50 μL / well, and the cells were lysed by agitation. 50 μL of the cell lysate and 50 μL of 2 mM DOPA-containing phosphate buffer were mixed and incubated at 37°C for 2 hours. The absorbance (measurement wavelength: 405 nm, reference wavelength: 650 nm) was measured, and the amount of DOPA-melanin was calculated from the calibration curve. The protein amount was quantified using a BCA protein assay kit (manufactured by Thermo), and the amount of DOPA-melanin per unit protein was calculated to confirm the tyrosinase biosynthesis inhibitory activity.

[0071] The results are shown in Figure 3. In Figure 3, "Control" is the negative control, which uses a medium to which no test sample has been added. DOPA-melanin (ng / µg protein) shown in Figure 3 is the amount of DOPA-melanin produced per unit protein; if tyrosinase biosynthesis is inhibited, the amount of DOPA-melanin is reduced. As can be seen from Figure 3, when methyllactic acid was added, a dose-dependent inhibitory effect on tyrosinase biosynthesis was observed.

[0072] Example 4: Tyrosinase protein expression inhibition test Cell culture conditions Normal human melanocytes (Kurabo Industries, Ltd.) were used as melanin-producing cells. Dermalife was used as the cell culture medium, and the cell concentration was 3 x 10 ５The volume was adjusted to 1.5 mL per cell and cultured in a 6-well plate at 37° C. in the presence of 5% carbon dioxide for 24 hours.

[0073] Test sample: The test sample was prepared by adding NaOH to methyl lactic acid to adjust the pH to 6.5, and the methyl lactic acid was added to Dermalife to a concentration of 20 mM. As a control, Dermalife without methyl lactic acid was used.

[0074] Measurement conditions for the inhibitory effect on tyrosinase protein expression The medium was replaced with the test sample (1.5 mL / well) and cultured for 48 hours. ＴＭ Proteins were extracted using Mammalian Protein Extraction Reagent (Thermo) and developed by SDS-PAGE. After transfer to a polyvinylidene fluoride (PVDF) membrane, the membrane was blocked with 5% skim milk. After reacting with an anti-tyrosinase antibody (Santa Cruz Biotechnology) for 1 hour, the membrane was further reacted with an HRP-labeled secondary antibody (abcam) for an additional 1 hour. Protein bands were detected using Ez West Blue W (ATTO). The signal intensity of the resulting bands was detected using the image processing software ImageJ, and the relative protein expression levels were calculated.

[0075] The results are shown in Figure 4. In Figure 4, "Control" is a negative control, which uses a medium to which no test sample has been added. Figure 4 also shows the relative expression level of tyrosinase protein; if the expression of tyrosinase protein is inhibited, the relative expression level of tyrosinase protein will be reduced. As can be seen from Figure 4, the addition of methyllactic acid showed an inhibitory effect on the expression of tyrosinase protein.

[0076] Example 5: Evaluation of suppression of mRNA expression of melanin synthesis-related factors Cell culture conditions Normal human melanocytes (Kurabo Industries, Ltd.) were used as melanin-producing cells. Dermalife was used as the cell culture medium, and the cell concentration was 3 × 10 ４The cells were adjusted to 100 cells / mL and cultured in a 96-well plate at 37° C. in the presence of 5% carbon dioxide for 24 hours.

[0077] Test sample: Methyl lactic acid was adjusted to pH 6.5 by adding NaOH to the test sample, and methyl lactic acid was added to Dermalife to a concentration of 10 or 20 mM. Dermalife without methyl lactic acid was used as a control.

[0078] Measurement conditions for the inhibitory effect on the mRNA expression of melanin synthesis-related factors: The medium was replaced with the test sample (100 μL / well) and cultured for 24 hours. After removing the medium, RNA was extracted using a Cells-to-Ct kit (manufactured by Thermo) and reverse-transcribed to synthesize cDNA. Real-time PCR was performed using the obtained cDNA to calculate the relative mRNA expression level.

[0079] The results are shown in Figure 5. In Figure 5, "Control" is a negative control, which is a medium containing no test sample. Figure 5 also shows the relative expression level of tylosinase mRNA, and the addition of methyllactic acid showed an inhibitory effect on the expression of tylosinase mRNA.

[0080] Formulation examples are shown below. The methyl lactic acid used in the following formulation examples is the same as that used in Example 1. Formulation Example 1: Whitening wipe-off lotion The ingredients shown in Table 2 below were dissolved with stirring at room temperature to prepare a whitening wipe-off lotion.

[0081] Formulation Example 2: Whitening lotion The ingredients shown in Table 3 below were dissolved with stirring at room temperature to prepare a whitening lotion.

[0082] Formulation Example 3: Whitening cream The ingredients shown in Table 4 below were dissolved with stirring at room temperature to prepare a whitening cream.

[0083] Formulation Example 4: Whitening emulsion The ingredients shown in Table 5 below were dissolved with stirring at room temperature to prepare a whitening emulsion.

[0084] Formulation Example 5: Whitening gel The ingredients shown in Table 6 below were dissolved with stirring at room temperature to prepare a whitening gel.

[0085] Formulation Example 6: Whitening serum The ingredients shown in Table 7 below were dissolved with stirring at room temperature to prepare a whitening serum.

[0086] Formulation Example 7: Whitening face wash The ingredients shown in Table 8 below were dissolved with stirring at room temperature to prepare a whitening face wash.

[0087] Formulation Example 8: Whitening soap The ingredients shown in Table 9 below were dissolved in a water bath at 80°C with stirring, and then cooled and solidified to prepare a whitening soap.

[0088] Example 6, Comparative Examples 1 to 3: Tests for Other Effects (Solubility in Oils and Fat) Oleic acid was added to a 50 wt % aqueous solution of an organic acid, and the mixture was stirred at room temperature (23°C) for 24 hours. If the saturated solubility of oleic acid at this time was 200 ppm or more, it was evaluated as A, and if it was less than 200 ppm, it was evaluated as B. (Solubility in Oils and Fat) Palmitic acid was added to a 50 wt % aqueous solution of an organic acid, and the mixture was stirred at room temperature (23°C) for 24 hours. If the saturated solubility of palmitic acid at this time was 20 ppm or more, it was evaluated as A, and if it was less than 20 ppm, it was evaluated as B.

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

[0090] The above test results show that methyl lactic acid has the ability to dissolve oils, dissolve fats and oils, perform chemical peeling, and remove acne bacteria, in addition to its melanin production inhibitory effect.

[0091] Although several embodiments of the present invention have been described, these embodiments are presented as examples and are not intended to limit the scope of the invention. These novel embodiments can be embodied in various other forms, and various omissions, substitutions, and modifications can be made without departing from the spirit of the invention. These embodiments and their modifications are included within the scope and spirit of the invention, and are also included in the scope of the invention and its equivalents as defined in the claims.

Claims

1. A melanin production inhibitor comprising a compound represented by formula (I) or a salt thereof: [In formula (I), R represents an alkyl group having 1 to 4 carbon atoms].

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

3. The melanin production inhibitor according to claim 1 or 2, further having any one or more of the following effects (a) to (d): (a) ability to dissolve oils; (b) ability to dissolve oils and fats; (c) chemical peeling ability; and (d) ability to remove acne bacteria.

4. A skin topical preparation comprising the melanin production inhibitor according to any one of claims 1 to 3.

5. The topical skin preparation according to claim 4, wherein the compound represented by formula (I) or its salt is contained in an amount of 0.001 to 50% by weight based on the weight of the topical skin preparation.

6. The topical skin preparation according to claim 4 or 5, further comprising one or more additives selected from the group consisting of thickeners, pH adjusters, preservatives and antioxidants.

7. The topical skin preparation according to claim 6, wherein the additives are each contained in an amount of 0.01 to 20% by weight based on the weight of the topical skin preparation.

8. The external skin preparation according to any one of claims 4 to 7, having a pH of 0.5 to 12.

9. The skin external preparation according to any one of claims 4 to 8, which is a whitening cosmetic preparation.

10. The external skin preparation according to claim 9, wherein the whitening cosmetic preparation is selected from the group consisting of lotion, cream, milky lotion, gel, serum, facial cleanser, soap, ointment, pack and foundation.

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