Melanin production inhibitors and topical skin preparations containing the same

Abstract

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

Description

Technology Field

[0001] The present invention relates to a melanin production inhibitor and a topical skin preparation containing the same. Background Technology

[0002] When skin is exposed to ultraviolet (UV) rays, such as those found in sunlight or UV lamps, it loses its radiance, texture, and moisture. In particular, if the dermis is damaged by UV rays, it causes wrinkles and sagging, which is the cause of what is known as photoaging. Reactive oxygen species generated by UV exposure, as well as various factors released from skin cells due to this influence, enhance the activity of tyrosinase in melanocytes. Melanin, which is involved in skin tone, is produced in melanocytes when tyrosine is oxidized by tyrosinase. It is believed that when tyrosinase is activated by UV rays, melanin is produced in excess, and as this excess melanin is transferred to epidermal cells, the skin tone changes and darkens.

[0003] Therefore, it is known that inhibiting the production of melanin is effective for obtaining a whitening effect, and known active ingredients that inhibit the production of melanin include ascorbic acid, kojic acid, arbutin, ellagic acid, 4-alkylesorcinol or derivatives thereof, or various plant extracts. In addition, it is known that a compound consisting of menthol and an ester of a long-chain unsaturated fatty acid having 18 or more carbon atoms is combined with an information-transmitting agent inhibitor, antioxidant, anti-inflammatory agent, polymeric compound, and polyhydric alcohol produced from keratinocytes to exhibit a high melanin production inhibiting effect due to a synergistic effect (e.g., Patent Document 1). Furthermore, it is known that cedrol, a component of sandalwood oil, exhibits a melanin production inhibiting effect (e.g., Patent Document 2), and nerolidol, a component of Cabruba oil, exhibits a melanin production inhibiting effect (e.g., Patent Document 3).

[0004] Meanwhile, vetiver extract is known to have a melanin-promoting effect (e.g., Patent Document 4).

[0005] As such, various components involved in melanin production are known, but in recent years, as the harmful effects of ultraviolet rays have become widely recognized, attention on melanin production inhibitors has been increasing. Prior art literature

[0006] Japanese Patent Publication No. 2007-161591, Japanese Patent Publication No. Hei 10-36246, Japanese Patent Publication No. Hei 6-72855, Japanese Patent Publication No. 2011-157317 The problem to be solved

[0007] The present invention aims to provide a melanin production inhibitor and a topical skin preparation containing the same. means of solving the problem

[0008] The inventors carefully examined the above problem and discovered that a compound having a predetermined structure or a salt thereof has a melanin production inhibitory effect, thereby completing the present invention. The present invention is, for example, as follows.

[0009] [1] Melanin production inhibitors comprising a compound represented by formula (I) or its salt:

[0010]

[0011] [In formula (I), R represents an alkyl group having 1 to 4 carbon atoms].

[0012] [2] A melanin-producing inhibitor described in [1], wherein R in formula (I) is a methyl group.

[0013] [3] A melanin-producing inhibitor described in [1] or [2] having one or more of the following effects (a) to (d):

[0014] (a) Solubility for oil

[0015] (b) Solubility for oils

[0016] (c) Chemical peeling ability

[0017] (d) Acne removal ability.

[0018] [4] A topical skin preparation containing a melanin production inhibitor described in any one of [1]~[3].

[0019] [5] The compound represented by the above formula (I) or its salt is included in an amount of 0.001 to 50 weight percent with respect to the above topical skin preparation, as described in [4].

[0020] [6] A topical skin preparation described in [4] or [5], further comprising one or more additives selected from the group consisting of thickeners, pH adjusters, preservatives and antioxidants.

[0021] [7] The above additives are included in an amount of 0.01 to 20 weight percent each with respect to the above topical skin preparation, as described in [6].

[0022] [8] A topical skin preparation with a pH of 0.5 to 12, as described in any one of [4] to [7].

[0023] [9] A skin external application described in any one of [4] to [8], which is a whitening cosmetic.

[0024]

[10] The above whitening cosmetic is a skin external preparation described in [9], selected from the group consisting of lotion, cream, emulsion, gel, beauty solution, facial wash, soap, ointment, pack and foundation. Effects of the invention

[0025] According to the present invention, a melanin production inhibitor and a topical skin preparation containing the same can be provided. Brief explanation of the drawing

[0026] Figure 1 is a diagram showing the results of Example 1. Figure 2 is a diagram showing the results of Example 2. Figure 3 is a diagram showing the results of Example 3. Figure 4 is a diagram showing the results of Example 4. Figure 5 is a diagram showing the results of Example 5. Specific details for implementing the invention

[0027] Hereinafter, embodiments of the present invention will be described in detail.

[0028] [1] Melanin production inhibitor

[0029] According to one embodiment of the present invention, a melanin production inhibitor comprising a compound represented by the following formula (I) or a salt thereof is provided:

[0030]

[0031] [In formula (I), R represents an alkyl group having 1 to 4 carbon atoms].

[0032] The alkyl group having 1 to 4 carbon atoms may be in a straight chain or a branched chain, and examples include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, t-butyl, etc. R is preferably methyl, ethyl, or isopropyl, more preferably methyl or ethyl, and particularly preferably methyl. The compound of formula (I) when R is methyl is 2-hydroxyisobutyric acid, and hereinafter this is also referred to as "methyl lactic acid".

[0033] As a salt of the compound of Formula (I), any pharmaceutically acceptable salt may be used, not limited to the above. Examples of such salts include sodium salts, potassium salts, magnesium salts, calcium salts, etc. Among these, sodium salts and potassium salts are preferred.

[0034] The melanin production inhibitor according to the embodiment can effectively inhibit melanin production. In addition, a topical skin preparation containing the said melanin production inhibitor is stable, highly safe, and has an excellent whitening effect. Although the reason for obtaining such effects is not certain, it is presumed as follows.

[0035] Melanin is biosynthesized in melanosomes, which are membrane organelles within pigment cells. It is hypothesized that melanin production can be inhibited by controlling the expression or activity of tyrosinase, which is thought to be the rate-limiting enzyme of this biosynthesis, with the compound of formula (I). It is hypothesized that by controlling the expression or activity of tyrosinase, the reaction converting tyrosine into dopaquinone and dopa is inhibited, and as a result, melanin production is inhibited.

[0036] As shown in the embodiments described below, the compound of formula (1) has an inhibitory effect on tyrosinase biosynthesis and an inhibitory effect on tyrosinase protein expression, and furthermore, has an inhibitory effect on the expression of melanin synthesis-related factor mRNA. Accordingly, according to one embodiment, a tyrosinase biosynthesis inhibitor comprising a compound represented by formula (1) or a salt thereof is provided. In addition, according to another embodiment, a tyrosinase protein expression inhibitor comprising a compound represented by formula (1) or a salt thereof is provided. According to an additional embodiment, a melanin synthesis-related factor mRNA expression inhibitor comprising a compound represented by formula (1) or a salt thereof is provided.

[0037] The melanin inhibitor according to the embodiment may be used in combination with other known melanin inhibitors (e.g., panthene-s-sulfonic acid, isoperulic 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 using a combination of multiple types of melanin inhibitors, they may be used simultaneously, sequentially, or separately. As described below, multiple types of melanin inhibitors may be combined in a single topical skin preparation.

[0038] [2] Topical application for the skin

[0039] According to another embodiment of the present invention, a topical skin preparation comprising the aforementioned melanin production inhibitor is provided.

[0040] The compound represented by the aforementioned formula (I) or its salt is included in the topical skin preparation in amounts of, for example, 0.001 to 50% by weight, 0.001 to 5% 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 melanin production inhibitory effect can be obtained. The content of the compound of formula (I) or its salt can be appropriately set according to the type or use of the topical skin preparation.

[0041] By utilizing the melanin production inhibitory effect, the aforementioned topical skin preparation can be used as a whitening cosmetic. As a whitening cosmetic, it is not particularly limited as long as it is applied to the skin, but examples include lotions, creams, emulsions, gels, beauty solutions, facial cleansers, soaps, ointments, packs, foundations, etc. Such whitening cosmetic can be manufactured according to commonly used formulation methods.

[0042] In addition to the melanin production inhibitor according to the embodiment, the topical skin preparation may include additives commonly used in cosmetics or pharmaceuticals. Examples of such additives include powder components, liquid oils, solid oils, waxes, hydrocarbon oils, higher fatty acids, higher alcohols, synthetic ester oils, silicones, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, moisturizers, 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 agents, fragrances, water, etc., and may be selected from among these and appropriately combined as needed. Among these, the topical skin preparation according to the embodiment preferably includes one or more additives selected from the group consisting of thickeners, pH adjusters, preservatives, and antioxidants.

[0043] Furthermore, other active ingredients and physiologically active ingredients, such as vitamins, skin revitalizers, blood circulation promoters, commensal bacteria control agents, free radical scavengers, anti-inflammatory agents, other whitening agents, and disinfectants, can be appropriately combined as needed.

[0044] The additives described above may be used as a single type or in combination. The amount of additives used is not particularly limited, but for example, they are added in an amount of 0.01 to 20% by weight, 0.01 to 5% by weight, or 0.01 to 1% by weight, respectively (per additive) with respect to the topical skin preparation. Additionally, it is preferable that the additives be added in a total amount of 0.1 to 50% by weight, 0.1 to 20% by weight, or 0.1 to 5% by weight with respect to the topical skin preparation. By including the additives in such amounts, the effect of the additive is fully exerted without interfering with the effect of the active ingredient, the compound of formula (I) or its salt.

[0045] Specific examples of additives are listed below.

[0046] As powder components, for example, talc, kaolin, mica, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, metal tungstate salts, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (plastered gypsum), calcium phosphate, hydroxyapatite, ceramic powder, metal soaps (zinc myristate, calcium palmitate, aluminum stearate), polyamide resin powder (nylon powder), polyethylene powder, methyl polymethacrylate powder, polystyrene powder, copolymer resin powder of styrene and acrylic acid, organic powders such as cellulose powder, inorganic white pigments such as titanium dioxide and zinc oxide; inorganic red pigments such as iron oxide (bengala) and iron titanate; inorganic purple pigments such as carbon black, manganese violet, and cobalt violet; and inorganic green pigments such as cobalt titanate; Inorganic blue pigments such as ultramarine and indigo; pearl pigments such as titanium-coated mica, titanium-coated bismuth oxychloride, titanium-coated talc, colored titanium-coated mica, bismuth oxychloride, and ichthyophrenia; metal powder pigments such as aluminum powder and copper powder; organic pigments such as Red 201, Red 202, Red 204, Red 205, Red 220, Red 226, Red 228, Red 405, Orange 203, Orange 204, Yellow 205, Yellow 401, and Blue 404; Examples include organic pigments such as zirconium, barium, or aluminum lakes, 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; and natural pigments such as chlorophyll and β-carotene. However, this powder ingredient may be any powder applicable to general cosmetics and is not limited to the above ingredients.

[0047] 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, flaxseed oil, safflower oil, cottonseed oil, soybean oil, peanut oil, tea seed oil, rice bran oil, jojoba oil, germ oil, triglycerin, trioctanogenic glycerin, triisopalmitic acid glycerin, etc.

[0048] Examples of solid fats include, for instance, cocoa fat, coconut oil, horse fat, hydrogenated coconut oil, palm oil, beef tallow, lamb fat, hydrogenated beef tallow, palm kernel oil, pork fat, bovine bone fat, beeswax kernel oil, hydrogenated oil, bovine gall fat, beeswax, hydrogenated castor oil, etc.

[0049] Examples of lead compounds include, for instance, beeswax, candelilla wax, cotton wax, rice bran wax, carnauba wax, bayberry wax, white wax, whale 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, POE hydrogenated lanolin alcohol ether, etc.

[0050] Examples of hydrocarbon oils include liquid paraffin, squalene, paraffin, squalane, petroleum jelly, and microcrystalline wax.

[0051] Examples of high-grade fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, 12-hydroxystearic acid, undecylenic acid, tol acid, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), etc.

[0052] Higher alcohols include, for example, straight-chain alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, behenyl alcohol, myristyl alcohol, oleyl alcohol, and cetostearyl alcohol; branched-chain alcohols such as monostearyl glycerin ether, 2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyldodecanol, isostearyl alcohol, and octyldodecanol.

[0053] As synthetic ester oils, for example, 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, 12-hydroxystearate cholesteryl, di-2-ethylhexylate ethylene glycol, dipentaerythritol fatty acid ester, neopentyl glycol dicaprate, diisostearyl malate, di-2-heptylundecanate glycerin, tri-2-ethylhexylate trimethylolpropane, triisostearyate trimethylolpropane, tetra-2-ethylhexylate Pentaerythritol, tri-2-ethylhexyl glycerin, triisostearis trimethylolpropane, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, trimiristic acid glycerin, tri-2-heptylundecanate glyceride, castor oil fatty acid methyl ester, oleic acid oil, cetostearyl alcohol, 2-heptylundecyl palmitate, diisobutyl adipic acid, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipic acid, ethyl laurate, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, 2-hexyldecyl adipic acid, diisopropyl sebate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate, etc. Can be lifted.

[0054] Examples of silicones include chain polysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane, and methylhydrogenpolysiloxane; alicyclic polysiloxanes such as decamethylpolysiloxane, dodecamethylpolysiloxane, and tetramethyltetrahydrogenpolysiloxane; silicone resins and silicone rubbers forming a three-dimensional network structure.

[0055] As anionic surfactants, for example, fatty acid soaps such as soap base, sodium laurate, sodium palmitate, etc.; higher alkyl sulfate ester salts such as sodium lauryl sulfate, potassium lauryl sulfate, etc.; alkyl ether sulfate ester salts such as POE lauryl sulfate triethanolamine, POE sodium lauryl sulfate, etc.; N-acyl sarcosic acid such as lauroyl sarcosine sodium; higher fatty acid amide sulfonates such as N-myristoyl-N-methyltaurine sodium, palm oil fatty acid methyltaurate sodium, lauryl methyltaurate sodium; phosphate ester salts such as POE oleyl ether phosphate sodium, POE stearyl ether phosphate, etc.; Sulfosuccinates such as di-2-ethylhexylsulfosuccinate sodium, monolauroyl monoethanolamide polyoxyethylene sulfosuccinate sodium, lauryl polypropylene glycol sulfosuccinate sodium; alkylbenzenesulfonates such as linear dodecylbenzenesulfonate sodium, linear dodecylbenzenesulfonic acid triethanolamine, linear dodecylbenzenesulfonic acid, etc.; N-acylglutamates such as N-lauroylglutamic acid monosodium, N-stearoylglutamic acid disodium, N-myristoyl-L-glutamic acid monosodium; higher fatty acid ester sulfate esters such as hydrogenated palm oil fatty acid glycerin sodium sulfate; sulfated oils such as lot oil; Examples include POE alkyl ether carboxylic acid, POE alkylallyl ether carboxylate, α-olefin sulfonate, higher fatty acid ester sulfonate, secondary alcohol sulfate ester, higher fatty acid alkylolamide sulfate ester, lauroyl monoethanolamide succinate sodium, N-palmitoyl aspartate ditriethanolamine, sodium caseinate, etc.

[0056] Examples of cationic surfactants include alkyl trimethylammonium salts such as stearyl trimethylammonium chloride and lauryl trimethylammonium chloride; alkylpyridinium salts such as distearyl dimethylammonium chloride, poly(N,N'-dimethyl-3,5-methylenepiperidinium chloride) and cetylpyridinium chloride; alkyl quaternary ammonium salts, alkyl dimethylbenzylammonium salts, alkyl isoquinolinium salts, dialkylmofolinium salts, POE alkylamines, alkylamine salts, polyamine fatty acid derivatives, amyl alcohol fatty acid derivatives, benzalkonium chloride, benzethonium chloride, etc.

[0057] Examples of amphoteric surfactants include imidazoline-based amphoteric surfactants such as 2-undecyl-N,N,N-(hydroxyethylcarboxymethyl)-2-imidazolin sodium, 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxydisodium salt; and betaine-based surfactants such as 2-heptadecyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryl dimethylaminoacetic acid betaine, alkyl betaine, amide betaine, and sulfobetaine.

[0058] Examples of lipophilic nonionic surfactants include sovitanic fatty acid esters such as sovitanic monooleate, sovitanic monoisostearate, sovitanic monolaurate, sovitanic monopalmitate, sovitanic monostearate, sovitanic sesquioleate, sovitanic trioleate, penta-2-ethylhexyl acid diglycerol sovitanic acid, tetra-2-ethylhexyl acid diglycerol sovitanic acid; glycerin polyglycerin fatty acids such as monocottonseed oil fatty acid glycerin, monoerucic acid glycerin, sesquioleic acid glycerin, monostearic acid glycerin, α,α'-oleic acid pyroglutamic acid glycerin, monostearic acid glycerin malate, propylene glycol fatty acid esters such as monostearic acid propylene glycol, hydrogenated castor oil derivatives, glycerin alkyl ethers, etc.

[0059] As hydrophilic nonionic surfactants, for example, POE sorbitan fatty acid esters such as POE sorbitan monooleate, POE sorbitan monostearate, POE sorbitan monooleate, POE sorbitan tetraoleate; POE sorbitan fatty acid esters such as POE sorbitan monolaurate, POE sorbitan monooleate, POE sorbitan pentaoleate, POE sorbitan monostearate; POE glycerin fatty acid esters such as POE glycerin monostearate, POE glycerin monoisostearate, POE glycerin triisostearate; POE fatty acid esters such as POE monooleate, POE distearate, POE monodioleate, and ethylene glycol distearate; POE alkyl ethers such as POE lauryl ether, POE oleyl ether, POE stearyl ether, POE behenyl ether, POE 2-octyldodecyl ether, POE cholestanol ether, etc.; POE alkylphenyl ethers such as POE octylphenyl ether, POE nonylphenyl ether, POE dinonylphenyl ether, etc.; Pluronic-type compounds 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, POE·POP glycerin ether, etc.; TetraPOE·TetraPOP ethylenediamine condensates such as Tetronic; POE castor oil derivatives such as POE castor oil, POE hydrogenated castor oil, POE hydrogenated castor oil monoisostearate, POE hydrogenated castor oil triisostearate, POE hydrogenated castor oil monopyroglutamic acid monoisostearic acid diester, POE hydrogenated castor oil maleic acid, etc.; POE wax and lanolin derivatives such as POE sobit beeswax, etc.; alkanolamides such as palm oil fatty acid diethanolamide, lauric acid monoethanolamide, fatty acid isopropanolamide, etc.;Examples include POE propylene glycol fatty acid esters, POE alkylamines, POE fatty acid amides, sucrose fatty acid esters, POE nonylphenyl formaldehyde condensates, alkylethoxydimethylamine oxides, trioleyl phosphoric acid, etc.;

[0060] Examples of moisturizers 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 salt, dl-pyrrolidone carboxylate, short-chain soluble collagen, diglycerin (EO) PO adduct, Roxburg rose extract, yarrow extract, merillote extract, etc.

[0061] 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 (brown algae 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.

[0062] 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 ester.

[0063] Examples of water-soluble polymer compounds for synthesis include vinyl-based polymer compounds such as polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, and carboxyvinyl polymer (e.g., "Carbopol" (registered trademark) from Lubrizol Advanced Materials); polyoxyethylene-based polymer compounds such as polyethylene glycol 20,000, 4,000,000, and 600,000; polyoxyethylene-polyoxypropylene copolymer-based polymer compounds; acrylic-based polymer compounds such as sodium polyacrylate, polyethyl acrylate, and polyacrylamide; polyethyleneimine, cationic polymers, etc.

[0064] Examples of water-soluble polymer compounds of inorganic materials include bentonite, AlMg silica (e.g., Bild’s “Bigum”), raponite, hectorite, anhydrous silica, etc.

[0065] Examples of thickeners include gum arabic, carrageenan, karaya gum, tragacanth gum, carob gum, quince seed, casein, dextrin, gelatin, sodium pectinate, sodium arginate, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium polyacrylate, carboxyvinyl polymer, cellulose dialkyldimethylammonium sulfate, xanthan gum, magnesium aluminum silicate, bentonite, etc.

[0066] As ultraviolet absorbers, for example, 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, N,N-dimethyl PABA octyl ester; anthranilic acid-based ultraviolet absorbers such as homomentyl-N-acetylanthranilate; salicylic acid-based ultraviolet absorbers such as amyl salicylate, menthyl salicylate, homomentyl salicylate, octyl salicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenyl salicylate; Cinnamate-based UV absorbers such as 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 (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-ethylhexane oil-diparamethoxycinnamate; Benzophenone-based ultraviolet absorbers such as 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-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, 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'-methylphenyl)benzotriazole, dibenzalazine, dianisoylmethane, 4-methoxy-4'-t-butyldibenzoylmethane, 5-(3,3-dimethyl-2-norvonylidene)-3-pentan-2-one, etc.;

[0067] Examples of sunscreens include titanium oxide, talc, carmine, bentonite, kaolin, zinc oxide, etc.

[0068] Examples of preservatives include methylparaben, ethylparaben, propylparaben, phenoxyethanol, sodium benzoate, etc.

[0069] Examples of metal ion chelating agents include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate, trisodium edetate, tetrasodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid, etc.

[0070] Examples of lower alcohols include methanol, ethanol, propanol, isopropanol, isobutyl alcohol, t-butyl alcohol, etc.

[0071] As polyhydric alcohols, for example, 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, octylene glycol, etc.; trihydric alcohols such as glycerin, trimethylolpropane, 1,2,6-hexanetriol, etc.; tetrahydric alcohols such as pentaerythritol, etc.; pentahydric alcohols such as xylitol, etc.; hexahydric alcohols such as sorbitol, mannitol, etc.; Polyhydric alcohol polymers such as diethylene glycol, dipropylene glycol, triethylene glycol, polypropylene glycol, tetraethylene glycol, diglycerin, polyethylene glycol, triglycerin, tetraglycerin, polyglycerin, etc., divalent alcohol alkyl ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene 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, ethylene glycol dibutyl ether, etc.; Divalent alcohol alkyl ethers 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;Divalent 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 diadifate, 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, propylene glycol monophenyl ether acetate, etc.; glycerin monoalkyl ethers such as kimyl alcohol, celakyl alcohol, batyl alcohol, etc.; Sugar alcohols such as sorbitol, maltitol, maltotriose, mannitol, sucrose, erythritol, glucose, fructose, starch hydrolysate, maltose, xylitose, and starch hydrolysate reducing alcohols; examples include glycolide, tetrahydrofurfuryl alcohol, POE tetrahydrofurfuryl alcohol, POP butyl ether, POP·POE butyl ether, tripolyoxypropylene glycerin ether, POP glycerin ether, POP glycerin ether phosphoric acid, POP·POE pentaerythritol ether, etc.;

[0072] As monosaccharides, for example, 3-carbon sugars such as D-glycerylaldehyde and dihydroxyacetone; 4-carbon sugars such as D-erythose, D-erythrulose, D-threose, and erythritol; 5-carbon sugars such as L-arabinose, D-xylose, L-rixose, D-arabinose, D-ribose, D-ribulose, D-xylulose, and L-xylulose; 6-carbon sugars such as D-glucose, D-talose, D-psicose, D-galactose, D-fructose, L-galactose, L-mannose, and D-tagatose; 7-carbon sugars such as aldoheptose and heptulose; 8-carbon sugars such as octulose; deoxysugars such as 2-deoxy-D-ribose, 6-deoxy-L-galactose, and 6-deoxy-L-mannose; Examples include 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-glucuronic acid, D-galacturonic acid, and L-iduronic acid.

[0073] Examples of oligosaccharides include sucrose, gentianose, umbelliferose, lactose, plantose, isorichnoses, α,α-trehalose, raffinose, lychnoses, umbilisin, stachyose, verbascose, etc.

[0074] Examples of polysaccharides include, for instance, cellulose, quince seed, chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, gum arabic, heparan sulfate, hyaluronic acid, tragacanth gum, chondroitin, xanthan gum, mucoitin sulfate, guar gum, dextran, caronic acid, etc.

[0075] 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.

[0076] Examples of amino acid derivatives include acyl sarcosine sodium (lauroyl sarcosine sodium), acyl glutamate, acyl β-alanine sodium, glutathione, pyrrolidone carboxylic acid, etc.

[0077] Examples of organic amines include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-methyl-1-propanol, etc.

[0078] Examples of synthetic resin emulsions include acrylic resin emulsions, ethyl polyacrylate emulsions, acrylic resin liquids, polyacrylic alkyl ester emulsions, vinyl polyacetic acid emulsions, etc.

[0079] Examples of pH adjusting agents include buffers such as malate-sodium malate, lactic acid-sodium lactate, and citric acid-sodium citrate.

[0080] Examples of vitamins include, for instance, vitamin A such as vitamin A oil and 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 ester, L-ascorbic acid monopalmitic acid ester, L-ascorbic acid dipalmitic acid ester, L-ascorbic acid-2-glucoside; pantothenic acid such as calcium pantothenate; vitamin D such as vitamin D2 and cholecalciferol; vitamin E such as α-tocopherol, tocopherol acetate, and DL-α-tocopherol nicotinate; pantothenic acid and its derivatives; biotin, etc.

[0081] Examples of antioxidants include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, gallic acid esters, etc. Examples of antioxidant auxiliary agents include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, kephalin, hexametaphosphate, phytic acid, ethylenediamine tetraacetic acid, etc.

[0082] The formulation of the topical skin preparation according to the embodiment is optional, and one or more of the aforementioned additives can be combined with the aforementioned melanin production inhibitor, such as a solution system, solubilization system, emulsion system, oil system, gel system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, etc., to adopt a formulation according to the intended product by conventional methods.

[0083] Meanwhile, it is known that multiple steps, such as tyrosinase-related processes and transport to the epidermis, are involved in the whitening effect, and the whitening effect can be strengthened by using a combination of various whitening compounds, including the representative whitening compound described in the background art.

[0084] The external skin preparation according to the embodiment preferably has a pH of 0.5 to 12, more preferably 3 to 7, and particularly preferably 3.5 to 7. By setting the pH to such a range, the melanin production inhibitory effect of the compound of formula (I) or its salt is exhibited more effectively. In addition, melanin production can be inhibited without killing commensal bacteria in the skin, including melanoma cells.

[0085] The melanin production inhibitor according to the embodiment may be formed into a fragrance composition by mixing one or more commonly used fragrance ingredients.

[0086] The "commonly used fragrance ingredients" mentioned here include various synthetic fragrances, natural essential oils, synthetic essential oils, citrus oils, animal-derived fragrances, etc. For example, a wide range of fragrance ingredients listed in "Perfume and Flavor Chemicals (Aroma Chemicals) 1, 2" (Steffen Arctender (1969)), "Synthetic Fragrance Chemistry and Product Knowledge <Expanded and Revised Edition>" by Motoichi Indo, published by Kagaku Kogyo Ippo, March 22, 2005, expanded and revised edition), and "Collection of Well-Known and Commonly Used Techniques (Fragrances) Part I" (published by the Japan Patent Office on January 29, 1999, Heisei 11) may be used. Representative examples among these include, for instance, α-pinene, limonene, cis-3-hexenol, phenylethyl alcohol, styralyl acetate, ammonium isovalerate, eugenol, rose oxide, linalool, benzaldehyde, muscone, Musk T (registered trademark, manufactured by Takasago Fragrance Industry Co., Ltd.), Thesalon (registered trademark, Takasago Fragrance Industry Co., Ltd.), and fragrances having a cooling effect, such as derivatives having a menthol or menthane backbone. By using these fragrances in combination with a melanin production inhibitor according to the embodiment, it is possible to improve the fragrance quality or scent profile of the prepared fragrance.

[0087] The melanin production inhibitor according to the embodiment may have not only the melanin production inhibitory effect as described above, but also additionally one or more of the following effects (a) to (d).

[0088] (a) Solubility for oil

[0089] (b) Solubility for oils

[0090] (c) Chemical peeling ability

[0091] (d) Acne removal ability

[0092] By combining the efficacy of (a) and / or (b), the melanin production inhibitor according to the embodiment has the effect of dissolving blackheads or excess sebum, and can bring about an effect of inhibiting melanin production to the deep layers of the skin, and is also useful in terms of improving skin roughness or acne.

[0093] By combining the efficacy of (c), the melanin production inhibitor according to the embodiment has the effect of removing unnecessary layers, and can bring about an effect of inhibiting melanin production to the deep layers of the skin, and is also useful in improving skin blemishes, dullness, fine lines, and acne.

[0094] By combining the efficacy of (d), the melanin production inhibitor according to the embodiment has the effect of eliminating acne bacteria, which are the causative agents of acne, and is also useful in terms of improving acne.

[0095] Here, oil refers to fatty acids that are liquid at room temperature, such as oleic acid, linoleic acid, linolenic acid, etc. Oil refers 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, stearic acid glyceride, etc.

[0096] A melanin production inhibitor according to an embodiment is preferably equipped with at least two of the above-mentioned effects (a) to (d) in order to improve acne and achieve a melanin-inhibiting effect deep within the skin. Furthermore, it is more preferable to equip it with at least three of the above-mentioned effects in order to improve skin roughness or acne and achieve a melanin-inhibiting effect deep within the skin, and it is even more preferable to equip it with all of the above effects in order to improve skin blemishes, dullness, fine lines, skin roughness, and acne, and achieve a melanin-inhibiting effect deep within the skin.

[0097] Examples

[0098] The present invention will be specifically described below with reference to examples, but the present invention is not limited thereto in any way, and various changes or modifications may be made without departing from the scope of the present invention. Meanwhile, regarding the units of the formulations described below, unless otherwise specified, "%" means "weight%", and the composition ratio indicates the weight ratio. Unless otherwise specified, the reagents used were those manufactured by Fujifilm Wako Junyaku. Methyl lactic acid was manufactured by Mitsubishi Gas Chemical.

[0099] <Example 1: Evaluation of Melanin Production Inhibitory Activity>

[0100] · Cell culture conditions

[0101] Mouse-derived skin melanoma cells B16 melanoma (JCRB0202, purchased from JCRB Cell Bank) were used as melanocytes. For the cell culture medium, 5 mL of 100 × penicillin streptomycin solution and 100 mL of non-inactivated fetal bovine serum (West Bio) were mixed into 500 mL of E-MEM medium. For subculture, cells were washed with phosphate buffer (GIBCO), detached from the container using 0.25% trypsin and EDTA (ethylenediaminetetraacetic acid), and isolated by centrifugation after adding medium. To ensure stable cell culture, the cell concentration was set to 5–16 × 10⁶. 4 Adjust to cells / mL, and use a 10cm petri dish or plastic culture flask (175cm 2 In ), it was cultured at 37°C in the presence of 5% carbon dioxide.

[0102] As the assay medium, a mixture of 5 mL of ×100 penicillin streptomycin solution, 100 mL of non-activated fetal bovine serum (West Bio) and 5 mL of GlutaMax ×100 (GIBCO) was used in 500 mL of D-MEM (phenol red-free, glutamic acid-free).

[0103] · Test Sample

[0104] As a test sample (methyl lactic acid 100 μM), methyl lactic acid was adjusted to pH=6.5 by adding NaOH, and methyl lactic acid was added to the assay medium to a concentration of 100 μM.

[0105]

[0106] · Conditions for measuring melanin production rate

[0107] Cells were detached from the culture obtained under the aforementioned cell culture conditions, and the cell concentration was 40×10 4 Cells and 1 mL of medium were seeded into each well of a 12-well container to achieve a cell / mL ratio. After 1 day of incubation, the medium was removed and replaced with test samples. After 1 day of incubation, the cells were washed with assay medium and 125 μL of 1 M NaOH was added to lyse the cells. 100 μL of this lysed cell solution was placed into a 96-well container. The absorbance at 450 nm was measured using a plate reader to calculate the melanin concentration.

[0108] The results are shown in Fig. 1. In Fig. 1, "medium only" is a negative control, and an assay medium without the test sample was used. "1 mM kojic acid" is a positive control, and an assay medium with 1 mM kojic acid, which is known to have an inhibitory effect on melanin production, was used.

[0109] The melanin production rate (%) shown in Figure 1 is a relative value (%) when the melanin concentration of the negative control is set to 100%, and is the average value of the values ​​measured for each of the 12 samples.

[0110] As can be seen from Figure 1, when methyl lactic acid was added, it exhibited a melanin production inhibitory effect equivalent to that of when kojic acid was added.

[0111] <Example 2: Cytotoxicity Test>

[0112] · Cell culture conditions

[0113] Cell culture was carried out in the same manner as in Example 1 described above.

[0114] · Test Sample

[0115] The test sample was prepared in the same manner as Example 1 described above.

[0116] · Cytotoxicity measurement conditions

[0117] Cells were detached from a culture obtained under the cell culture conditions shown in Example 1, and the cell concentration was 5×10 4 Cells and 0.1 mL of medium were seeded into each 96-well plate to achieve a cell / mL ratio. After 1 day of incubation, the medium was removed and replaced with test samples. After an additional 1 day of incubation, the plates were washed with assay medium, and 0.1 mL of a solution containing Cell Counting Kit 8 and medium mixed in a 1:9 ratio was added to each well. After standing at 37°C for 30 minutes in the presence of 5% carbon dioxide, the absorbance at 450 nm was measured using a plate reader to calculate the cell count.

[0118] The results are shown in Figure 2. The cell count (%) is the relative value (%) when the cell count of the negative control (medium only) is set to 100%, and is the average value of the values ​​measured for each of the 16 samples.

[0119] As can be seen from Figure 2, no cytotoxicity was confirmed when methyl lactic acid was added.

[0120] <Example 3: Tyrosinase Biosynthesis Inhibitory Activity Test>

[0121] · Cell culture conditions

[0122] Normal human melanocytes (Gurabose) were used as melanocytes. Dermalife (Gurabose) was used as the cell culture medium, and the cell concentration was 3×10⁻⁶ 4 The cell / mL concentration was adjusted, and the cells were cultured in a 96-well plate at 37°C for 24 hours in the presence of 5% carbon dioxide.

[0123] · Test Sample

[0124] As a test sample, methyl lactic acid was adjusted to pH=6.5 by adding NaOH, and methyl lactic acid was added to Dermalife at concentrations of 2.5, 5, 10, 20, and 40 mM. As a control, Dermalife without added methyl lactic acid was used.

[0125] · Measurement conditions for tyrosinase biosynthesis inhibitory activity

[0126] The medium was removed from the culture obtained under the aforementioned cell culture conditions and replaced with the test sample. After 1 day of culture, the medium was removed, and phosphate buffer containing 0.5% Triton X-100 was added to a volume of 50 μL / well, and the cells were lysed by agitation. 50 μL of the cell lysate was mixed with 50 μL of phosphate buffer containing 2 mM DOPA, and the mixture was incubated at 37°C for 2 hours. Absorbance (measurement wavelength: 405 nm, reference wavelength: 650 nm) was measured, and the amount of DOPA-melanin was calculated from the calibration curve. Protein content was quantified using a BCA protein assay kit (Thermoje), and the amount of DOPA-melanin per unit protein was calculated to confirm the inhibitory effect on tyrosinase biosynthesis.

[0127] The results are shown in Fig. 3. In Fig. 3, "Control" is a negative control, and a medium was used without adding the test sample.

[0128] DOPA-melanin (ng / μg protein) shown in Figure 3 is the amount of DOPA-melanin produced per unit protein, and if the biosynthesis of tyrosinase is inhibited, the amount of DOPA-melanin is reduced.

[0129] As can be seen from Figure 3, when methyl lactic acid was added, it exhibited a quantity-dependent inhibitory effect on tyrosinase biosynthesis.

[0130] <Example 4: Tyrosinase Protein Expression Inhibition Test>

[0131] · Cell culture conditions

[0132] Normal human melanocytes (Grabose) were used as melanocytes. Dermalife was used as the cell culture medium, and the cell concentration was 3×10⁻⁶ 5 The cell volume was adjusted to 1.5 mL / cell and cultured in a 6-well plate at 37°C for 24 hours in the presence of 5% carbon dioxide.

[0133] · Test Sample

[0134] As a test sample, methyl lactic acid was adjusted to pH=6.5 by adding NaOH, and methyl lactic acid was added to Dermalife to a concentration of 20 mM. As a control, Dermalife without added methyl lactic acid was used.

[0135] · Measurement conditions for tyrosinase protein expression inhibitory action

[0136] The medium was replaced with the test sample (1.5 mL / well) and incubated for 48 hours. After removing the medium, M-PER TMProteins were extracted using Mammalian Protein Extraction Reagent (Thermo) and separated by SDS-PAGE. After transferring to a polyfluoride vinylidene membrane (PVDF), the membrane was blocked with 5% skim milk. After reacting with an anti-tyrosinase antibody (Santa Cruz Biotechnology) for 1 hour, the membrane was reacted for an additional 1 hour with an HRP-labeled secondary antibody (abcam). Protein bands were detected using Ez West Blue W (ATTO). The signal intensity of the obtained bands was analyzed using the image processing software ImageJ, and the relative protein expression levels were calculated.

[0137] The results are shown in Fig. 4. In Fig. 4, "Control" is a negative control, and a medium was used without adding the test sample.

[0138] Figure 4 shows the relative expression level of tyrosinase protein, and if the expression of tyrosinase protein is inhibited, the relative expression level of tyrosinase protein is reduced.

[0139] As can be seen from Figure 4, when methyl lactic acid was added, it exhibited an inhibitory effect on the expression of tyrosinase protein.

[0140] <Example 5: Evaluation of Inhibition of mRNA Expression of Melanin Synthesis-Related Factors>

[0141] · Cell culture conditions

[0142] Normal human melanocytes (Grabose) were used as melanocytes. Dermalife was used as the cell culture medium, and the cell concentration was 3×10⁻⁶ 4 The cell / mL concentration was adjusted, and the cells were cultured in a 96-well plate at 37°C for 24 hours in the presence of 5% carbon dioxide.

[0143] · Test Sample

[0144] As a test sample, methyl lactic acid was adjusted to pH=6.5 by adding NaOH, and methyl lactic acid was added to Dermalife to a concentration of 10 and 20 mM. As a control, Dermalife without added methyl lactic acid was used.

[0145] · Measurement conditions for the inhibitory effect of mRNA expression of melanin synthesis-related factors

[0146] The medium was replaced with the test sample (100 μL / well) and cultured for 24 hours. After removing the medium, RNA was extracted using the Cells-to-Ct kit (Thermoze), and cDNA was synthesized by performing reverse transcription. Real-time PCR was performed using the obtained cDNA to calculate the relative expression level of mRNA.

[0147] The results are shown in Fig. 5. In Fig. 5, "Control" is a negative control, and a medium was used without adding the test sample.

[0148] Figure 5 shows the relative expression levels of Tylosinaze mRNA, and when methyl lactic acid was added, it showed an inhibitory effect on the expression of Tylosinaze mRNA.

[0149] Examples of formulations are shown below. The methyl lactic acid used in the following examples of formulations is the same as that used in Example 1.

[0150] <Prescription Example 1> Whitening wipe-off lotion

[0151] A whitening wipe-off lotion was prepared by dissolving the ingredients shown in Table 2 below while stirring at room temperature.

[0152]

[0153] <Prescription Example 2> Whitening lotion

[0154] A whitening lotion was prepared by dissolving the ingredients shown in Table 3 below while stirring at room temperature.

[0155]

[0156] <Prescription Example 3> Whitening Cream

[0157] A whitening cream was prepared by dissolving the ingredients shown in Table 4 below while stirring at room temperature.

[0158]

[0159] <Prescription Example 4> Whitening Emulsion

[0160] A whitening emulsion was prepared by dissolving the ingredients shown in Table 5 below while stirring at room temperature.

[0161]

[0162] <Prescription Example 5> Whitening Gel

[0163] A whitening gel was prepared by dissolving the ingredients shown in Table 6 below while stirring at room temperature.

[0164]

[0165] <Prescription Example 6> Whitening Beauty Solution

[0166] A whitening cosmetic solution was prepared by dissolving the ingredients shown in Table 7 below while stirring at room temperature.

[0167]

[0168] <Prescription Example 7> Whitening facial cleanser

[0169] A whitening facial cleanser was prepared by dissolving the ingredients shown in Table 8 below while stirring at room temperature.

[0170]

[0171] <Prescription Example 8> Whitening Soap

[0172] The ingredients shown in Table 9 below were dissolved in an 80°C bath while stirring, then cooled and solidified to prepare a whitening soap.

[0173]

[0174] <Example 6, Comparative Examples 1–3: Tests regarding other efficacy>

[0175] (Solubility for oil)

[0176] Oleic acid was added to a 50% by weight aqueous solution of organic acid and stirred at room temperature (23℃) for 24 hours. If the saturated solubility of oleic acid at that time was 200 ppm or more, it was evaluated as A, and if it was less than 200 ppm, it was evaluated as B.

[0177] (Solubility of oils)

[0178] Palmitic acid was added to a 50% by weight aqueous solution of organic acid and stirred at room temperature (23℃) for 24 hours. If the saturated solubility of palmitic acid at that time was 20 ppm or more, it was evaluated as A, and if it was less than 20 ppm, it was evaluated as B.

[0179] (Chemical peeling ability)

[0180] A 7% by weight aqueous solution of organic acid was applied to pig skin for 24 hours, and if the thickness of each layer decreased by 10% or more, it was evaluated as A, and if it decreased by less than 10%, it was evaluated as B.

[0181] (Acne removal ability)

[0182] 0.05 mL of a 7 wt% aqueous solution of organic acid was added dropwise to 5 mL of a test solution prepared with the strain Cutibacterium acnes NBRC 107605 at a concentration of 108 CFU / mL. The result was evaluated as A if the number of viable cells after 60 seconds was less than 1%, and B if it was 1% or more.

[0183]

[0184] From the above test results, it can be seen that methyl lactic acid possesses, in addition to the effect of inhibiting melanin production, solubility for oil, solubility for grease, chemical peeling ability, and acne removal ability.

[0185] Although some 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 may be implemented in various other forms, and various omissions, substitutions, and modifications may be made without departing from the essence of the invention. These embodiments and their variations are included within the scope and essence of the invention and are also included within the scope equivalent to the invention described in the claims.

Claims

Claim 1 Melanin production inhibitors 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]. Claim 2 A melanin production inhibitor according to claim 1, wherein R in formula (I) is a methyl group. Claim 3 A melanin production inhibitor according to claim 1 or 2, additionally having one or more of the following effects: (a) solubility for oil (b) solubility for grease (c) chemical peeling ability (d) acne removal ability. Claim 4 A topical skin preparation comprising a melanin production inhibitor described in any one of paragraphs 1 to 3. Claim 5 In claim 4, the compound represented by formula (I) or its salt is included in an amount of 0.001 to 50 weight percent with respect to the topical skin preparation. Claim 6 A 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. Claim 7 In claim 6, the above additive is included in an amount of 0.01 to 20 weight percent each with respect to the above topical skin preparation. Claim 8 A topical skin preparation having a pH of 0.5 to 12 in any one of paragraphs 4 to 7. Claim 9 In any one of paragraphs 4 through 8, a skin external preparation that is a whitening cosmetic. Claim 10 In claim 9, the whitening cosmetic is a skin external preparation selected from the group consisting of lotion, cream, emulsion, gel, beauty solution, facial cleanser, soap, ointment, pack, and foundation.

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