JP7037780B2 - Whitening agent - Google Patents

Description

The present invention relates to a tyrosinase activity inhibitor characterized by containing indole as an active ingredient and a whitening agent containing the same.

Ultraviolet light produces black melanin in the melanocytes in the basal layer of the epidermis.
Normally, it is sufficient that this black melanin is properly excreted by skin turnover, but the imbalance is lost and black melamine is accumulated in the epidermis, which is a spot spot.

Since this black melanin is produced by tyrosinase, a substance that inhibits tyrosinase activity has been conventionally used as a whitening agent.

Tyrosinase (EC114.18.1) is a biological enzyme that oxidizes L-tyrosine to L-dopa and also oxidizes L-dopa to dopaquinone. Since dopaquinone is a causative substance of melanin that induces spots and freckles, it is considered that it is possible to prevent the formation of spots and freckles by inhibiting tyrosinase.

As a substance that inhibits such tyrosinase activity, a substance containing ascorbic acid and its derivative, a hydroquinone derivative, pyrones such as kojic acid, a placenta extract such as placenta extract, and the like has been proposed, and these substances are melanin. Although it is disclosed as a substance having a whitening effect such as suppression of production and a light-colored bleaching effect of produced melanin, there is no substance using indole.

Indole has an LD50 value of 1000 mg / kg bw when orally administered to rats (JECFA WHO FOOD ADDITIVES SERIES 54 (2006)), and an LD50 value of 790 mg / kg bw when administered transdermally to rabbits (JECFA WHO FOOD ADDITIVES SERIES 54 (2006)). RTECS (2003), original literature American Industrial Hygiene Association Journal. Vol23, page95 (1962)), and in a study in which male rats were fed a diet for 21 days, the high dose group was 375 mg / kg / day (90-day correction). : 87.5 mg / kg / day) It has been reported that there is no significant difference between the treated group and the control group except for the decrease in food intake and weight gain up to the equivalent dose (JECFA WHO FOOD ADDITIVES SERIES). 54 (2006)), and in a study in which a dose equivalent to 100 mg / kgbw / day was fed to rats for 560 days, reversible and mild anemia was observed, but no adverse effects including histopathological examination were reported. (JECFA WHO FOOD ADDITIVES SERIES 54 (2006)).

Furthermore, indole is known to be produced by Escherichia coli in the human intestine, but indole-producing bacteria such as Proteus glugaris, Providencia SPP, and Morganella spp exist in addition to Escherichia coli. It is said that the indole produced by the intestinal flora of Escherichia coli may suppress the pathogenicity of pathogenic bacteria such as Salmonella ( https://www.mishima-kaiun.or.jp/assist/report_pdfnaname/ ). 2012n / n_h24_03pdf )

Therefore, even when indole is used as a whitening agent, food, health food, etc., it has a large safety margin, and thus the present invention has industrial applicability.

Indole is solid at room temperature and has a fecal odor, but at low concentrations it has a jasmine or orange-like scent, so it is used as a raw material for perfumes and fragrances. It is known that indole is used as one of the common fragrances in a cosmetic perfume kit in order to obtain a cosmetic having a desired fragrance tone (Patent Document 1). Further, an antioxidant containing an indole derivative, for example, indole-3-carboxylic acid (Patent Document 2) is known.

Japanese Unexamined Patent Publication No. 2011-12016 Japanese Unexamined Patent Publication No. 2014-198790

As a result of diligent research on an excellent whitening agent, the present inventors have found that indole has a strong whitening effect, and have completed the present invention.

That is, the present invention is a tyrosinase activity inhibitor characterized by containing indole as an active ingredient.

Furthermore, the present invention is a whitening agent comprising the tyrosinase activity inhibitor .

Furthermore, the present invention is any of gel, milky lotion, oil, serum, sheet mask, face pack, body soap, body milk, lotion, cleansing agent, cream, foundation, white powder and sunscreen cosmetics. It is a feature.

Furthermore, the present invention is a food product comprising the tyrosinase activity inhibitor .
Furthermore, the present invention is characterized by being a whitening food or a whitening health food.

Indole, which is a whitening component of the present invention, has a strong inhibitory effect on tyrosinase activity and is therefore excellent as a whitening agent.
Indole is a compound having a wide safety margin for the human body, and since it inhibits tyrosinase activity in a concentration-dependent manner, it has an advantage that it is easy to adjust the blending amount to obtain the effect.
That is, a desired whitening effect can be obtained by increasing the blending amount when a strong whitening effect is required and decreasing the blending amount when a mild whitening effect is required.
Further, since indole has a jasmine or orange-like scent at a dilute concentration, the whitening agent of the present invention also has an advantage that a preferable scent can be obtained without special scenting.

The whitening agent of the present invention may contain indole as an active ingredient, and may be either indole alone or composed of indole and various carriers.

In the present invention, the indole as an active ingredient varies depending on the method of using the whitening agent, the age, body weight, nutritional status of the user, etc., but is generally 1 mg to 20 mg, preferably 5 mg to 10 mg per 1 kg of body weight. It is compounded.

In the present invention, the indole as an active ingredient may be a chemically synthesized product or may be derived from a natural product. The indole by chemical synthesis may be produced by a known method, for example, an indole produced by a gas phase reaction of aniline and ethylene glycol in the presence of a catalyst, benzene and 2-aminoethanol. Examples thereof include those produced by undergoing a gas phase reaction in the presence of a catalyst.

In addition, as natural products, microorganisms, for example, indole produced by culturing a microorganism belonging to the genus Enterobactor and having an ability to produce indole from tryptophan in a medium containing tryptophan, or Moso bamboo, Matake, and light bamboo, etc. Examples thereof include an extract obtained by steam distillation of bamboos, or an extract obtained by extracting this with an organic solvent such as ethyl acetate or hexane. Further, it may be an indole derived from fossil fuels such as petroleum and coal.

The whitening agent of the present invention can be used in various cosmetics such as pharmaceuticals, basic cosmetics and make-up cosmetics, foods, health foods and the like. For example, the pharmaceutical product may be an oral preparation, a coating agent, or a liquid preparation, and the cosmetic product can be used for any of basic cosmetics and make-up cosmetics, and can be used as cosmetics for both men and women. .. Further, it may be a cosmeceutical product or a general cosmetic product.

When the whitening agent of the present invention is used as a drug, indole is generally 0.01% or more in the drug, although it varies depending on the type of drug, age, body weight, nutritional status, administration method, administration route, etc. of the drug. It is blended so as to be 0.8%, preferably 0.05% to 0.3%.

When the whitening agent of the present invention is used as a pharmaceutical product, it may be used as it is or mixed with a pharmacologically acceptable carrier by a commonly known method of a pharmaceutical product, an administration method, or a pharmaceutical preparation. For example, it can be a solid preparation such as a tablet, a powder, a granule, a capsule, a suppository, or an ointment, or a preparation such as an injection, an emulsion, a suspension, a syrup, an elixir, or a lotion. Pharmacologically acceptable carriers include, for example, excipients, lubricants, binders and disintegrants in solid formulations, or solvents, lysis aids, suspending agents, isotonic agents and buffers in liquid formulations. Examples thereof include pharmaceutical aids such as agents and pain-relieving agents. Further, if necessary, an appropriate amount of additives such as ordinary preservatives, antioxidants, colorants, sweeteners, adsorbents, and wetting agents can be used.

When the whitening agent of the present invention is used as cosmetics, it varies depending on the type of cosmetics, the age, weight, nutritional status, frequency of use, etc. of the user who uses the cosmetics, but indole is generally 0.01 in the cosmetics. It is blended so as to be% to 0.8%, preferably 0.05% to 0.5%.

Basic cosmetics include general lotion, soft lotion, astringent lotion, whitening lotion, vegetable lotion, acne lotion, alkaline lotion, wipe-off lotion, pre-skin lotion, lotion, after-shave lotion, carmine lotion. Toners, emulsions, cleansing lotions, cleansing gels, cleansing milks, cleansing creams, cleansing oils and other cleansing agents, cold creams, nourishing creams, vanishing creams, night creams, eye creams, hand creams, lip creams, body creams, etc. Creams such as, facial masks, etc.
Further, as basic cosmetics, various gels, various milky lotions, various oils, various beauty essences, sheet masks, face packs, body soaps, body milks and the like can be mentioned.

Examples of make-up cosmetics include cake type, powder type, mineral foundation, cream type, liquid type and other foundations, eyebrow powder, eyebrow mascara and other eyebrows, white powder, and sunscreen cosmetics.

These cosmetics may have a plurality of functions in one agent, and may contain a makeup base, a foundation, etc., such as BB cream, CC cream, and all-in-one cosmetics. good.

These cosmetics can be produced by a known production method using a known carrier, and the carriers include powder components, fats and oils, waxes, hydrocarbon oils, higher fatty acids, higher alcohols, and synthetic ester oils. , Silicone oil, surfactant, moisturizer, water-soluble polymer, thickener, film agent, ultraviolet absorber, metal ion blocker, lower alcohol, polyhydric alcohol, sugar, amino acid, organic amine, polymer emulsion, pH adjusters, skin nutrients, vitamins, antioxidants, antioxidant aids and the like can be used, and these can be blended with one or more.

Examples of the powder component include an inorganic powder component and an organic powder component. Examples of the inorganic powder component include talc, kaolin, mica, silk mica (serisite), white mica, gold mica, synthetic mica, red mica, black mica, permiculite, magnesium carbonate, calcium carbonate, aluminum silicate, and silicic acid. Barium, calcium silicate, magnesium silicate, strontium silicate, metal tungstate, magnesium, silica, zeolite, barium sulfate, calcined calcium sulfate (baked sekko), calcium phosphate, fluoroapatite, hydroxyapatite, ceramic powder, metal soap ( For example, zinc myristate, calcium palmitate, aluminum stearate), boron nitride, etc.

Examples of the organic powder include polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, styrene and acrylic acid copolymer resin powder, benzoguanamine resin powder, polytetrafluorated ethylene powder, and cellulose. Examples include powder.

These powders may be pigments, for example, inorganic white pigments such as titanium dioxide and zinc oxide, inorganic red pigments such as iron oxide (bengala) and iron titanate, and inorganic brown pigments such as γ-iron oxide. Pigments, inorganic black pigments such as black iron oxide and low-order titanium oxide, inorganic purple pigments such as mango violet and cobalt violet, inorganic green pigments such as chromium oxide, chromium hydroxide and cobalt titanate, ultramarine and professional Examples thereof include inorganic blue pigments such as cyan blue, titanium oxide coated mica, titanium oxide coated bismuth chloride, titanium oxide coated talc, colored titanium oxide coated mica, bismuth oxychloride, and pearl pigments such as fish scale foil.

In addition, as pigments, metal powder pigments such as aluminum powder and copper powder,
Red 3, Red 104, Red 106, Red 201, Red 202, Red 204, Red 205, Red 220, Red 226, Red 227, Red 228, Red 230, Red 401 No., Red No. 405, Red No. 505, Orange No. 203, Orange No. 204, Orange No. 205, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203, Yellow No. 205, Yellow No. 401, Blue No. 1, Examples include organic pigments such as Blue No. 404 and Green No. 3, and natural pigments such as chlorophyll and β-carotene.

Examples of fats and oils include avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, southern ka oil, castor oil, and flaxseed oil. Liquid oils such as safflower oil, cottonseed oil, eno oil, soybean oil, peanut oil, teaseed oil, kaya oil, rice bran oil, cinnamon oil, Japanese millet oil, jojoba oil, germ oil, and triglycerin. Also, for example, coconut oil, palm oil, horse fat, hardened palm oil, palm oil, beef fat, sheep fat, hardened beef fat, palm kernel oil, pork fat, beef bone fat, mokurou kernel oil, hardened oil, beef leg fat, etc. Examples include solid oils and fats such as hydrogenated coconut oil.

Examples of waxes include beeswax, candelilla wax, mokurou, cotton wax, carnauba wax, bayberry wax, sardine wax, whale wax, montan wax, lanolin, lanolin, capoc wax, lanolin acetate, liquid lanolin, sugar cane, lanolin fatty acid isopropyl, and hexyl laurate. Examples thereof include reduced lanolin, jojobaro, hard lanolin, celac wax, polyoxyethylene (hereinafter referred to as POE) lanolin alcohol ether, POE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol, and POE hydrogenated lanolin alcohol ether.

Examples of the hydrocarbon oil include liquid paraffin, zokerite, squalane, pristane, paraffin, selecin, squalene, petrolatum, and microcrystalline wax.

Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, undecylenic acid, tortic acid, isostearic acid, linoleic acid, linoleic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid ( DHA) and the like.

Higher alcohols include, for example, linear alcohols (eg, lauryl alcohols, cetyl alcohols, stearyl alcohols, behenyl alcohols, myristyl alcohols, oleyl alcohols, cetostearyl alcohols, etc.); branched chain alcohols (eg, monostearyl glycerin ethers (batyl alcohols). ), 2-Deciltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyldodecanol, isostearyl alcohol, octyldodecanol, etc.).

Synthetic ester oils include isopropyl myristate, cetyl octanate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate. , Lanorin acetate, Isocetyl stearate, Isocetyl isostearate, Cholesteryl 12-hydroxystearate, Ethylene glycol di2-ethylhexanate, Dipentaerythritol fatty acid ester, N-alkylglycol monoisostearate, Neopentyl glycol dicaprate, Apple acid Diisostearyl, glycerin di2-heptylundecanoate, trimethylolpropane tri2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythritol tetra2-ethylhexanoate, glycerin tri2-ethylhexanoate, glycerin trioctanoate, Glycerin triisopalmitate, trimethylolpropane triisostearate, cetyl 2-ethylhexanate, 2-ethylhexyl palmitate, glycerin trimyristate, glyceride tri2-heptylundecanoic acid, methyl ester of castor oil fatty acid, oleyl oleate, aceto Glyceride, 2-heptylundecyl palmitate, diisobutyl adipate, 2-octyldodecyl ester of N-lauroyl-L-glutamate, di2-heptylundesyl adipate, ethyllaurate, di2-ethylhexyl sebacate, 2 myristic acid -Hexyldecyl, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, triethyl citrate and the like can be mentioned.

Silicone oils include, for example, chain polysiloxanes (eg, dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane, etc.); cyclic polysiloxanes (eg, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexane). (Sasiloxane, etc.)) Silicone resin, silicone rubber, and various modified polysiloxanes (amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, fluorine-modified polysiloxane, etc.) that form a three-dimensional network structure are listed. Be done.

Examples of the surfactant include anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants.

Examples of the anionic surfactant include fatty acid salts such as sodium laurate and sodium palmitate, higher alkyl sulfate ester salts such as sodium lauryl sulfate and potassium lauryl sulfate, and alkyl such as POE lauryl sulfate triethanolamine and POE sodium lauryl sulfate. N-acylsarcosic acid such as ether sulfate ester salt and sodium lauroyl sarcosinate, higher fatty acid amide sulfonates such as N-myristoyl-N-methyltaurine sodium, coconut oil fatty acid methyltaurid sodium, laurylmethyltaurid sodium, POE oleyl Phosphoric acid ester salts such as sodium ether phosphate and POE stearyl ether phosphate, sulfosuccinates such as sodium di2-ethylhexyl sulfosuccinate, monolauroyl monoethanolamide polyoxyethylene sodium sulfosuccinate, and sodium lauryl polypropylene glycol sulfosuccinate. Be done.

Furthermore, alkylbenzene sulfonates such as sodium nearadodecylbenzenesulfonate, triethanolamine lineardodecylbenzenesulfonic acid, lineardodecylbenzenesulfonic acid, higher fatty acid ester sulfates such as hardened coconut oil fatty acid glycerin sulfate, and N-lauroyl. N-acylglutamates such as monosodium glutamate, disodium N-stearoylglutamate, monosodium N-myristyl-L-monosodium glutamate, sulfated oils such as funnel oil, POE alkyl ether carboxylic acid, POE alkyl allyl ether carboxylic acid, etc. Acid, α-olefin sulfonate, higher fatty acid ester sulfonate, secondary alcohol sulfate ester salt, higher fatty acid alkylrolamide sulfate ester salt, sodium lauroyl monoethanolamide succinate, N-palmitoyle aspartate ditriethanolamine, Examples include sodium caseinate.

Examples of the cationic surfactant include an alkyltrimethylammonium salt such as stearyltrimethylammonium chloride and lauryltrimethylammonium chloride, an alkylpyridinium salt such as cetylpyridinium chloride, a distearyldimethylammonium dialkyldimethylammonium salt, and poly (N, N) chloride. '-Dimethyl-3,5-methylenepiperidinium), alkyl quaternary ammonium salt, alkyldimethylbenzylammonium salt, alkylisoquinolinium salt, dialkylmoriphonium salt, POE alkylamine, alkylamine salt, polyamine fatty acid derivative , Ammonium alcohol fatty acid derivative, benzalconium chloride, benzethonium chloride and the like.

Examples of amphoteric surfactants include 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium and 2-cocoyl-2-imidazolinium hydroxyside-1-carboxyethyroxy 2. Imidazoline amphoteric surfactants such as sodium salt, 2-heptadecyl-N-carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkylbetaine, amide betaine, sulfobetaine and other betaine surfactants. And so on.

Examples of the nonionic surfactant include sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, and penta2-ethylhexylate. Solbitan fatty acid esters such as diglycerol sorbitan and tetra2-ethylhexyl acid diglycerol sorbitan, monocotton oil fatty acid glycerin, monoerucate glycerin, sesquioleate glycerin, monostearate glycerin, α, α'-pyroglutamate oleate glycerin, mono Glycerin polyglycerin fatty acids such as glycerin stearate, propylene glycol fatty acid esters such as propylene glycol monostearate, hardened castor oil derivative, glycerin alkyl ether, POE sorbitan monooleate, POE sorbitan monostearate, POE sorbitan mono POE sorbitan fatty acid esters such as oleate and POE sorbitan tetraoleate, POE sorbit fatty acid esters such as POE sorbit monolaurate, POE sorbit monooleate, POE sorbit pentaoleate, POE sorbit monostearate, POE glycerin monosteer POE glycerin fatty acid esters such as rate, POE glycerin monoisostearate, POE glycerin triisostearate, POE glycerin fatty acid esters such as POE distearate, POE monodiolate, ethylene glycol distearate, POE lauryl ether, POE oleyl POE alkyl ethers such as ether, POE stearyl ether, POE behenyl ether, POE2-octyldodecyl ether, POE cholestanol ether, pluronic types such as pluronic, POE / POP-cetyl ether, POE / POP-2-decyltetradecyl POE / POP (polyoxypropylene) alkyl ethers such as ether, POE / POP-monobutyl ether, POE / POP-hydrogenated lanolin, POE / POP-glycerin ether, tetra POE / tetra POP-ethylenediamine condensate such as Tetronic Kind, POE Glyceride Oil, POE Hardened Glyceride Oil, POE Hardened Glyceride Oil Monoisostearate, POE Hardened Glyceride Oil Triisostearate Rate, POE hardened bean oil monopyroglutamic acid monoisostearic acid diester, POE hardened bean oil hardened bean oil derivative such as maleic acid, POE-mitsuro lanolin derivative such as POE sorbit honey, coconut oil fatty acid diethanolamide, lauric acid Examples thereof include alkanolamides such as monoethanolamide and fatty acid isopropanolamide, POE-propylene glycol fatty acid ester, POE alkylamine, POE fatty acid amide, sucrose fatty acid ester, alkylethoxydimethylamine oxide, and trioleyl phosphate.

Moisturizing agents include, for example, polyethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, xylitol, sorbitol, martitol, chondroitin sulfate, hyaluronic acid, mucoitin sulfate, caronic acid, atelocollagen, cholesteryl-12-hydroxystearate. , Sodium lactate, bile acid salt, dl-pyrrolidone carboxylate, short chain soluble collagen, diglycerin (EO) PO adduct, Izayoi rose extract, sardine extract, melilot extract and the like.

Natural water-soluble polymers include, for example, ala-avia gum, tragacanto gum, galactan, guar gum, carob gum, karaya gum, carrageenan, pectin, canten, quince seed (malmero), algae colloid (cassow extract), rice starch, corn starch, potato starch, etc. Examples thereof include plant-based polymers such as wheat starch, microbial-based polymers such as glycyrrhizic acid, xanthan gum, dextran, succinoglucan, and burran, and animal-based polymers such as collagen, casein, albumin, and gelatin.

Examples of the semi-synthetic water-soluble polymer include starch-based polymers such as carboxymethyl starch and methyl hydroxypropyl starch, methyl cellulose, ethyl cellulose, methyl hydroxypropyl cellulose, hydroxyethyl cellulose, sodium cellulose sulfate, hydroxypropyl cellulose, and carboxymethyl cellulose. Examples thereof include cellulosic polymers such as sodium carboxymethyl cellulose, and alginic acid polymers such as sodium ruginate and propylene glycol alginate.

Examples of the water-soluble synthetic polymer include vinyl polymers such as polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, and carboxyvinyl polymers, PEG20,000, PEG40,000, PEG60,000, and POE / POP copolymers. Examples thereof include polyoxyethylene polymers, acrylic polymers such as sodium polyacrylate and polyacrylamide, polyethyleneimine, and cationic polymers.

Examples of the thickener include Arabic gum, carrageenan, karaya gum, tragacanto gum, carob gum, quince seed (malmero), casein, dextrin, gelatin, sodium pectinate, sodium araginate, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, and the like. Hydroxyethyl cellulose, hydroxypropyl cellulose, PVA, PVM, PVP, sodium polyacrylate, carboxyvinyl polymer, locust bean gum, guar gum, tamarint gum, dialkyldimethylammonium sulfate cellulose, xanthan gum, aluminum magnesium silicate, bentonite, hectrite, silicic acid. Examples thereof include A1Mg (bea gum), laponite, and anhydrous silicic acid.

Examples of the ultraviolet absorber include para-aminobenzoic acid (PABA), PABA monoglycerin ester, N, N-dipropoxy PABA ethyl ester, N, N-diethoxy PABA ethyl ester, N, N-dimethyl PABA ethyl ester, N, N. -A benzoic acid-based ultraviolet absorber such as dimethyl PABA butyl ester and N, N-dimethyl PABA ethyl ester can be mentioned. In addition, anthranylic acid-based ultraviolet absorbers such as homomentyl-N-acetylanthranilate, salicylic acid-based ultraviolet absorbers such as amylsalicylate, mentylsalicylate, homomentylsalicylate, octylsalicylate, phenylsalicylate, benzylsalicylate, and p-isopropanolphenylsalicylate. , Octyl cinnamate, ethyl-4-isopropyl cinnamate, methyl-2,5-diisopropyl cinnamate, ethyl-2,4-diisopropyl cinnamate, methyl-2,4-diisopropyl cinnamate, propyl-p-methoxy cinnamate , Isoamyl-p-methoxysinamate, isoamyl-p-methoxysinamate, octyl-p-methoxysinamate (2-ethylhexyl-p-methoxysinamate), 2-ethoxyethyl-p-methoxysinamate, cyclohexyl-p -Methoxycinnamate, ethyl-α-cyano-β-phenylcinnamate, 2-ethylhexyl-α-cyano-β-phenylcinnamate, glycerylmono-2-ethylhexanoyl-diparamethoxycinnamate, trimethoxycinnamate Examples thereof include lauric acid-based ultraviolet absorbers such as methylbis (trimethylsiloxy) silylisopentyl and the like. 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-based UV absorbers such as benzophenone-2-carboxylate, 2-hydroxy-4-n-octoxybenzophenone, 4-hydroxy-3-carboxybenzophenone, 3- (4'-methylbenziliden) -d, l-camper , 3-Bendylidene-d, l-Camfer, 2-Phenyl-5-Methylbenzophenone, 2,2'-Hydroxy-5-Methylphenylbenzotriazole, 2- (2'-Hydroxy-5'-t-octyl) Phenyl) benzotriazole, 2- (2'-hydroxy-5'-methylphenylbenzotriazole, dibenzalazine, dianisoilmethane, 4-methoxy-4'-t-butyldibenzoylmethane, 5- (3,3-dimethyl-) 2-Norborniliden) -3-pentan-2-one and the like.

Examples of the metal ion sequestering agent include 1-hydroxyethane-1,1-diphosphonic acid, 1-hydroxyethane-1,1-diphosphonic acid tetrasodium salt, disodium edetate, trisodium edetate, and tetrasodium edetate. , Sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, phosphoric acid, citric acid, ascorbic acid, succinic acid, edetic acid, ethylenediamine hydroxyethyl triacetate trisodium and the like.

Examples of the lower alcohol include ethanol, propanol, isopropanol, isobutyl alcohol, t-butyl alcohol and the like.

Examples of the polyhydric alcohol include ethylene glycol, propylene glycol, trimethylene glycol, 1,2-butylene glycol, 1,3-BG, tetramethylene glycol, 2,3-butylene glycol, pentamethylene glycol, and 2 -Butene-1,4-diol, hexylene glycol, octylene glycol and other dihydric alcohols, glycerin, trimethylolpropane and other trihydric alcohols, pentaerythritol and other tetrahydric alcohols, xylitol and other pentahydric alcohols, sorbitol and mannitol. Examples thereof include hexahydric alcohols such as, diethylene glycol, dipropylene glycol, triethylene glycol, polypropylene glycol, tetraethylene glycol, diglycerin, PEG, triglycerin, tetraglycerin, polyglycerin and other polyhydric alcohol polymers.

In addition, EG monomethyl ether, EG monoethyl ether, EG monobutyl ether, EG monophenyl ether, EG monohexyl ether, EG mono2-methylhexyl ether, EG isoamyl ether, EGbenzyl ether, EGisopropyl ether, EGdimethyl ether, EGdiethyl Ether, EG dibutyl ether, 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, PG monomethyl ether , PG monoethyl ether, PG monobutyl ether, PG isopropyl ether, dipropylene glycol methyl ether, dipropylene glycol ethyl ether, dipropylene glycol butyl ether and other dihydric alcohol alkyl ethers.

Furthermore, EG monomethyl ether acetate, EG monoethyl ether acetate, EG monobutyl ether acetate, EG monophenyl ether acetate, EG diazibate, EG disuccinate, diethylene glycol monoethyl ether estate, diethylene glycol monobutyl ether acetate, PG monomethyl ether acetate, PG mono Divalent alcohol ether esters such as ethyl ether acetate, PG monopropyl ether acetate, PG monophenyl ether acetate, glycerin monoalkyl ethers such as xyl alcohol, seraquil alcohol, bacillus alcohol, sorbitol, martitol, maltotriose, mannitol , Sugar alcohols such as sucrose, erythritol, glucose, fructose, starch-degrading sugar, maltose, xylitos, starch-degrading sugar-reduced alcohol, glycolid, 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-pentane erythritol ether, polyglycerin and the like can be mentioned.

Examples of the monosaccharide include tricarboses such as D-glycerylaldehyde and dihydroxyacetone, tetracarboses such as D-erythrose, D-elittlerose, D-treose, and erythritol, L-arabinose, D-xylulose, and L-lyxylose. , D-arabinose, D-ribose, D-libulose, D-xylulose, L-xylulose and other deoxysaccharides, D-glucose, D-talose, D-busicose, D-galactose, D-fructose, L-galactose, Six-carbon sugars such as L-mannose and D-tagatose, aldoheptose, heplulose, etc.; Deoxy-L-mannose, etc .; deoxy sugar, D-glucosamine, D-galactosemin, sialic acid, aminouronic acid, amino sugars such as muramic acid, D-glucuronic acid, D-mannuronic acid, L-gluronic acid, D-galacturone Examples thereof include uronic acid such as acid and L-isulonic acid.

Examples of oligosaccharides include sucrose, gunthianose, umbelliferose, lactose, planteose, isolikunoses, α, α-trehalose, raffinose, lycnoses, umbilicin, stachyose velvas and the like.

Examples of polysaccharides include cellulose, quince seed, chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, Arabic gum, heparan sulfate, hyaluronic acid, tragant gum, keratan sulfate, chondroitin, xanthan gum, mucoitin sulfate, guagam, dextran, and kerato sulfate. , Locust bin gum, succinoglucan, caronic acid, etc.

Examples of amino acids include neutral amino acids such as threonine and cysteine, and basic amino acids such as hydroxylysine. Examples of the amino acid derivative include acyl sarcosine sodium (lauroyl sarcosine sodium), acyl glutamate, acyl β-alanine sodium, glutathione, and pyrrolidone carboxylic acid.

Examples of the organic amine include monoethanolamine, diethanolamine, triethanolamine, morpholine, triisopropanolamine, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-methyl-1-propanol and the like. Can be given.

Examples of the polymer emulsion include an acrylic resin emulsion, an ethylpolyacrylic acid emulsion, an acrylic resin liquid, a polyacrylic alkyl ester emulsion, a polyvinyl acetate resin emulsion, and a natural rubber latex.

Examples of the pH adjusting agent include buffers such as lactic acid-sodium lactate and citric acid-sodium citrate.
Examples of vitamins include vitamins A, B ₁ , B ₂ , B ₆ , C, E and their derivatives, pantothenic acid and its derivatives, biotin and the like.

Examples of the antioxidant include tocopherols, dibutylhydroxytoluene, butylhydroxyanisole, gallic acid esters and the like.

Examples of the antioxidant aid include phosphoric acid, citric acid, ascorbic acid, maleic acid, malonic acid, succinic acid, fumaric acid, kephalin, hexametaphosphate, phytic acid, ethylenediamine tetraacetic acid and the like.

Examples of other compoundable components include preservatives such as ethylparaben and butylparaben, and anti-inflammatory agents such as glycyrrhizinic acid derivative, glycyrrhetinic acid derivative, salicylic acid derivative, hinokithiol, zinc oxide, and allantin.

Further, a whitening agent other than the whitening ingredient of the present invention may be blended, and such whitening agents include, for example, vitamin C, magnesium ascorbic acid phosphate, ascorbic acid glucoside, arbutin, kodiic acid, aubaku, auren, and cicon. , Shakyaku, Senburi, Birch, Sage, Biwa, Carrot, Aloe, Zeniaoi, Iris, Grape, Yokuinin, Hechima, Yuri, Saffron, Senkyu, Shokyu, Otogirisou, Ononis, Carrot, Togarashi, Chimpi, Touki, Seaweed, etc. Various extracts from, for example, royal jelly, photosensitizers, activators such as cholesterol derivatives, nonyl acid valenylamide, nicotinic acid benzyl ester, nicotinic acid β-butoxyethyl ester, capsaicin, zingeron, cantalist tincture, ictamol, tannic acid, Blood circulation promoters such as α-borneol, tocopherol nicotinate, inositol hexanicotinate, cyclanderate, cinnaridine, trazoline, acetylcholine, verapamil, cepharanthin, γ-orizanol, antilipidides such as sulfur and thiantoll, tranexamic acid, thiotaurine. , Anti-inflammatory agents such as hypotaurine.

Cosmetics using the whitening agent of the present invention can be produced according to a conventional method by blending the above-mentioned ingredients.

Further, the present invention is a whitening food and a whitening health food containing indole as an active ingredient.
The whitening food or health food for whitening of the present invention contains indole in addition to the edible component in the food or health food.

In the whitening food or health food for whitening of the present invention, the indole varies depending on the type of food or health food, the age, weight, nutritional status of the eater, etc., but is generally 0.01% to 0.8 in the food. % May be blended, preferably 0.05% to 0.5% blended.

In the present invention, the edible component in foods or health foods includes ordinary foods such as processed foods such as confectionery, prepared foods and frozen foods, oral foods such as mouth refreshers and gums, and various vitamin preparations. Supplements etc.

By dissolving and adding indole in hot water or hot alcohol during or after the production of these edible components, the whitening food or health food for whitening of the present invention can be obtained.

Further, it can be used as one of the raw materials for producing the edible portion, and can be produced as a food or a health food by a known production method together with other edible components.
Since the indole used in the present invention is extremely small and has a scent such as orange, it is convenient because the addition of a fragrance can be omitted as a whitening food or a health food for whitening.

Further, in the supplement, a dosage form such as powder, tablet, granule, fine granule, microcapsule, capsule, etc. can be adopted. It can be added to the process or formulation.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention can be carried out in various other forms without departing from its spirit or main characteristics. Therefore, the above-described embodiment is merely an example in all respects, and the scope of the present invention is shown in the claims and is not bound by the text of the specification. Further, all modifications and modifications that fall within the scope of the claims are within the scope of the present invention.

Experimental Example 1
<Tyrosinase activity inhibitory action>
The inhibitory effect of indole on tyrosinase activity was investigated.
Enzyme solution (derived from mushroom) suspended in a substrate (100 μl) containing 0.1 mol of L-dopa in an indole solution (20 μl) dissolved in a phosphate buffer solution (pH 6.8) containing 20% DMSO at different concentrations. Tyrosinase 30U (20 μl manufactured by Sigma) was mixed well and subjected to an enzymatic reaction in a constant temperature bath at 37 ° C. for 15 minutes. Then, a 0.1 N HCl aqueous solution (20 μl) was added as a reaction stop solution (S). At the same time, one using a phosphate buffer instead of the substrate and the sample (SB1) and one using a phosphate buffer instead of the sample (B1) were prepared.

After the enzymatic reaction, the absorbance at 475 nm was measured using a phosphate buffer (pH 6.8) as a measurement blank, and the tyrosinase activity inhibition rate (%) was calculated according to the following formula.

Inhibition rate (%) = B1- (S-SB1) / B1 × 100

The results are shown in Table 1, and indole inhibited the activity of tyrosinase in a concentration-dependent manner.

Example 1
<Manufacturing of vanishing cream>
Indole 0.2
Stearic acid 5.0
Stearyl alcohol 4.0
Butyl stearate alcohol ester 8.0
Glycerin monostearic acid ester 2.0
Propylene glycol 10.0
Glycerin 4.0
Potassium hydroxide 0.2
Preservatives / Antioxidants Appropriate amount Fragrance Appropriate amount Purified water residue The above composition indicates that it is by weight.

Propylene glycol, potassium hydroxide and indole are added to purified water to dissolve them, and the mixture is heated and kept at 70 ° C. (aqueous phase). Other components are mixed and melted by heating and kept at 70 ° C (oil phase). The oil phase is gradually added to the aqueous phase, and after all the addition is completed, the temperature is maintained for a while to cause a reaction. Then, it was uniformly emulsified with a homomixer and cooled to 30 ° C. with good stirring to produce a whitening vanishing cream.

Example 2
<Manufacturing of cold cream>
Indole 0.2
Solid paraffin 5.0
Beeswax 10.0
Vaseline 15.0
Liquid paraffin 41.0
Glycerin monostearic acid ester
Polyoxyethylene 2.0
Sorbitan monolauric acid ester 2.0
Butylated hydroxytoluene 0.4
Soap powder 0.1
Purified water Residual fragrance Appropriate amount Preservative Appropriate amount

Soap powder, seaweed extract and indole are added to purified water, dissolved by heating and kept at 70 ° C. (aqueous phase). Ingredients other than the above are mixed, heated and melted, and kept at 70 ° C. (oil phase). Gradually add the oil phase to the aqueous phase while stirring, and after the addition is complete, keep the temperature for a while to cause a reaction. Then, it was uniformly emulsified with a homomixer and cooled to 30 ° C. with good stirring to produce a whitening cold cream.

Example 3
<Manufacturing of emulsion>
Indole 0.2
Microcrystalline wax 1.0
Beeswax 2.0
Lanolin 20.0
Liquid paraffin 10.0
Squalene 5.0
Sorbitan sesquioleic acid ester 4.0
Polyoxyethylene (20 mol)
Sorbitan monooleic acid ester 1.0
Propylene glycol 7.0
Purified water Residual fragrance Appropriate amount Preservative / Antioxidant Appropriate amount

Polyethylene glycol, triethanolamine and indole are added to purified water, dissolved by heating and kept at 70 ° C. (aqueous phase). Other components are mixed and melted by heating and kept at 70 ° C (oil phase). A whitening emulsion was produced by adding an oil phase to an aqueous phase, pre-emulsifying it, emulsifying it uniformly with a homomixer, and then cooling it to 30 ° C. with good stirring after emulsification.

Example 4
<Manufacturing of lotion>
(Alcohol phase)
95% Ethyl Alcohol 10.0
Polyoxyethylene hydrogenated castor oil 2.0
Propylene glycol 0.1
Oleyl alcohol 0.1
Lecithin 2.5

(Water phase)
Indole 0.2
Glycerin 5.0
Purified water residual UV absorber Appropriate amount

A whitening lotion was produced by mixing and dissolving each component of the alcohol phase and the aqueous phase, and then solubilizing the aqueous phase and the alcohol phase, respectively.

Example 5
<Manufacturing of peel-off type pack>
(Alcohol phase)
95% ethanol 10.0
Polyoxyethylene (15 mol)
Oleyl alcohol ether 2.0
Preservatives Appropriate amount Fragrances Appropriate amount

(Water phase)
Indole 0.2
Polyvinyl alcohol 12.0
Glycerin 3.0
Polyethylene glycol 1500 1.0
Purified water residue

The components of the aqueous phase are mixed and dissolved in purified water at 80 ° C. to prepare an aqueous phase liquid, and the mixture is cooled to 50 ° C. Each component of the alcohol phase is mixed and dissolved in polyvinyl alcohol at room temperature to prepare an aqueous phase solution. An alcohol phase solution was added to the aqueous phase solution, mixed until uniform, and allowed to cool to produce a whitening peel-off type pack.

Example 6
<Manufacturing of whitening skin lotion>
(A) Ingredients Ethanol 10.0
Monolauric acid
Polyoxyethylene (20 mol) sorbitan 5.0
Dibutylhydroxytoluene 0.01
Fragrance 0.05

(B) Indole 0.2
Glycerin 5.0
Xanthan gum 0.1
Hydroxyethyl cellulose 0.1
Purified water residue

After the above component (A) was mixed and uniformly dissolved, the component (B) was further added, stirred and dispersed, and then filled in a container to produce a whitening skin lotion.

Example 7
<Manufacturing sunscreen cream>
(A) Ingredients Oil-based glyceryl monostearate 0.1
Polyoxyethylene cetyl ether 0.1
Polyoxyethylene sorbitol tetraoleate 0.05
Behenyl alcohol 5.0
Triethylhexanoin 7.0
Ethylhexyl methoxycinnamate 6.0
Oxybenzone 2.0

(B) Ingredients Xanthan gum 0.3
Lysine sodium dilauroyl glutamate 0.1
1, 3 Butylene glycol 0.1
Indole 0.2
Purified water residue

After stirring and mixing the component (A) and the component (B) to 80 ° C., the component (A) is added to the component (B) while stirring at 80 ° C. with a homomixer (5000 rpm). Continue stirring for 5 minutes at 80 ° C. Then, the sunscreen cream was produced by cooling the room with stirring.

Example 8
<Manufacturing of cleansing gel>
(A) Indole 0.2
Sodium dilauroyl glutamate 0.3
Glycerin 20.0
Sorbitol 3.5
Purified water residue

(B) Ingredients Liquid paraffin 47.0
Isononyl isononanoate 15.0
Methylpolysiloxane 5.0
Decamethylcyclopentasiloxane 5.0
Polyoxyethylene triisostearate glyceryl 2.0

The component (A) is stirred at 40 ° C. for 5 minutes (800 rpm) and then at room temperature for 15 minutes (800 rpm). The component (B) is added with stirring (800 rpm) at about 1 g / min for the first 10 minutes, and then added with stirring (800 rpm) at about 3 g / min. The defoaming treatment was performed three times to produce a cleansing gel.

Example 9
<Manufacturing of cleansing milk>
(A) Indole 0.2
Glycerin 7.5
Glycerin fatty acid ester 0.5
Purified water residue

(B) Ingredient Polyglyceryl diisostearate 7.0
Polyglyceryl distearate 3.0
Tri (caprylic acid / capric acid) glyceryl 55.5

(C) Ingredients Xanthan gum 0.05
Purified water 4.95

The component (A) is heated and dissolved at 80 ° C., and the component (B) is heated and dissolved at 80 ° C., mixed with a homomixer (6000 rpm) and stirred. Then, it was cooled (about 35 ° C.), and then the component (C) was added while stirring with a paddle to produce cleansing milk.

Example 10
<Manufacturing of beauty essence>
(A) Ingredient 1,3 Butylene glycol 5.0
Glycerin 5.0
Xanthan gum 0.5
Hydroxyethyl cellulose 0.5
Sodium hyaluronate 0.2

(B) Ingredients Preservatives Appropriate amount Chelating agent 0.1
Purified water residue

(C) Indole 0.2
Sodium citrate Appropriate amount Citric acid Appropriate amount

The other components are stirred and dispersed in the components (A) 1,3 butylene glycol and glycerin. (B) A chelating agent and a preservative are stirred and dissolved in a heated (70 ° C.) purified water of the component, and then cooled to about 40 ° C. Then, the component (A) is mixed with the component (B) and stirred. After confirming the stirring and dissolution of (A) and (B), the pH was adjusted with the component (C) to produce a beauty essence.

Example 11
<Manufacturing of beauty supplements>
(Product raw material)
Indole 0.2
Beeswax 5.0
Glycerin fatty acid ester 2.0
γ-Tocopherol 3.0
Olive oil residue

Each raw material was mixed and wrapped in a gelatin film to produce a soft capsule beauty supplement.

Claims (1)

A tyrosinase activity inhibitor characterized by containing indole as an active ingredient.