JP6389308B1 - Topical skin preparation - Google Patents

Abstract

An object of the present invention is to find a novel whitening component and to provide a skin external preparation, a whitening skin external preparation and a whitening agent containing the novel whitening component. [MEANS FOR SOLVING PROBLEMS] As a result of conducting tests on a large number of plant extracts that have not yet been examined for whitening effects in order to find a new whitening component, a high whitening effect on rotogenic acid contained in the extract of the peony of Rubiaceae plants. I found. Therefore, the present inventors provide a skin external preparation, a whitening skin external preparation and a whitening agent containing rotgenic acid. [Selection figure] None

Description

  The present invention relates to a skin external preparation, a whitening skin external preparation, and a whitening agent.

  For cosmetic purposes, pigmentation such as stains and buckwheat on the skin is regarded as a problem, and it has been proposed to add ingredients such as arbutin, ascorbic acid derivatives, and kojic acid that suppress pigmentation to skin cosmetics. However, ultraviolet rays reaching the epidermis due to air pollution and ozone layer destruction are increasing year by year, and new components effective for preventing and improving the corresponding pigmentation are required. (Patent Documents 1 to 3)

  Therefore, although it has been reported that a whitening effect such as polyphenol derived from walnuts has been reported as a component that replaces the conventional whitening component, an effect superior to that of the conventional whitening component has not been confirmed (Patent Document 4).

JP 9-20610 A JP-A-4-182492 JP-A-2-200262 JP2008-81408

  An object of the present invention is to find a novel whitening component and provide a skin external preparation, a whitening skin external preparation and a whitening agent containing the novel whitening component.

  In order to find a new whitening component, a number of plant extracts that have not yet been examined for whitening have been tested. As a result, a whitening effect has been found in the extract of Rubiaceae, and it is also included in the vulture extract. Rotogenic acid found high whitening effect. Therefore, the present inventors provide a skin external preparation, a whitening skin external preparation and a whitening agent containing rotgenic acid.

That is, the present invention includes the following items.
[Item 1] A skin external preparation containing rotgenic acid or a salt thereof.
[Item 2] An external preparation for skin whitening containing rotgenic acid or a salt thereof.
[Item 3] A whitening agent containing rotgenic acid or a salt thereof.
[Item 4] A skin external preparation containing a bald gluten extract that essentially contains rotgenic acid or a salt thereof.
[Item 5] A skin whitening external preparation for skin whitening, which contains a bald gluten extract that essentially contains rotgenic acid or a salt thereof.
[Item 6] A whitening agent comprising a bald gluten extract that essentially contains rotgenic acid or a salt thereof.

  ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to provide the skin external preparation which has the plant-derived safe and outstanding whitening effect, the skin external preparation for whitening, and the whitening agent.

Rotogenic acid LC / MS chart It is a figure which shows the tyrosinase gene expression inhibitory effect of rotgenic acid.

  As used herein, the term “vulture” refers to the root of Rubiaceae plant: vulture (Scientific name: Morinda officinalis).

  The vulture extract used in the present invention preferably uses vulture roots, but in addition, one or more selected from flowers, leaves, seeds and the like can be used. Moreover, an extract is obtained by adding a solvent to the pressing liquid and / or residue obtained after performing a pressing process other than what is obtained by extracting directly from these various extraction parts using a solvent. Are also included within the scope of the definition of extract in the present invention.

  As an extraction solvent for obtaining the balsene extract used in the present invention, an organic solvent such as methanol, ethanol, butylene glycol or the like is preferable. However, when it is not preferable to use a solvent depending on the application, the solvent can be easily removed after extraction. Alternatively, a method of performing extraction using a highly volatile solvent and dissolving in water or butylene glycol after the solvent is removed is also possible. Moreover, you may perform extraction extraction suitably.

  Regarding the extraction method, the temperature of the solvent, the weight ratio of the solvent to the raw material, or the extraction time can be arbitrarily set for various raw materials and the solvent used. The temperature of the solvent can be arbitrarily set in the range of −4 ° C. to 100 ° C., but is preferably around 10 to 40 ° C. from the viewpoint of the stability of the components contained in the raw material. Also, the weight ratio of the solvent to the raw material can be arbitrarily set within a range of, for example, raw material: solvent of 4: 1 to 1: 100, and a weight ratio of 1: 1 to 1:20 is particularly preferable.

  The vulture extract used in the present invention can be further subjected to a refining operation after solvent extraction. The refining operation includes acid (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, organic acid, etc.) or alkali (water). Decomposition by adding sodium oxide, calcium hydroxide, ammonia, etc., fermentation or metabolic conversion by microorganisms, component adsorption by ion exchange resin, activated carbon, diatomaceous earth, etc., various separation modes (ion exchange, hydrophilic adsorption, hydrophobic adsorption) Fractionation using chromatography with size exclusion, ligand exchange, affinity, etc.), filtration using filter paper, membrane filter, ultrafiltration membrane, etc., pressurization or decompression, heating or cooling, drying, pH Examples include adjustment, deodorization, decolorization, and long-term stationary storage, and it is possible to arbitrarily select and combine them.

The compound in the form of rotgenic acid and / or pharmaceutically acceptable salt represented by the following chemical structural formula (formula 1) used in the present invention can be obtained by extraction, synthesis, etc. from plants, animals, fungi and the like. In addition, since the bald gluten extract in the present invention contains a large amount of rotgenic acid, purification using a column or the like may be used. Examples thereof include monovalent or divalent or higher inorganic salts such as sodium, potassium, calcium, magnesium and zinc, organic salts such as organic amines and basic amino acids, or salts formed by combinations thereof.

  In producing the skin external preparation, whitening skin external preparation, whitening agent of the present invention, the form of the baldgeten extract, rotgenic acid or rotgenic acid salt used is liquid, solid, powder, paste, etc. Any shape may be used, and an optimum shape for carrying out the present invention can be arbitrarily selected.

  The content of the vulture extract in the various compositions of the present invention is not particularly limited as long as it can be confirmed that the expression of tyrosinase can be suppressed, but generally 0.01 mg / g to 200 mg / g (denominator). Indicates the weight of the preparation). Preferably it is in the range of 0.1 mg / g to 20 mg / g, most preferably the bald gluten extract is 200 μg / g to 10 mg / g. Rotogenic acid and / or a pharmaceutically acceptable salt is not particularly limited as long as it can be confirmed that the expression of tyrosinase can be suppressed, but it is preferably 0.00004 to 5% by weight. This is because the inhibitory effect in the case of 0.00004% by weight (about 0.8 μM) was higher than the inhibitory effect of Tyrosinase gene expression on B16 melanoma cells at 0.000005% by weight (about 0.1 μM) of rotgenic acid, and This is because the use feeling of the external preparation was better when 5% by weight of rotogenic acid was added than when 7% by weight of rotogenic acid was added.

  The dosage form of the external preparation for skin, the external preparation for whitening, and the whitening agent according to the present invention is arbitrary, and ampoules, capsules, powders, granules, pills, tablets, solids, liquids, gels, bubbles , Emulsion, cream, ointment, sheet, mousse, powder dispersion, multilayer, aerosol, and the like.

  Specific skin external preparations and whitening skin external preparations (including preparations used for animals) include ampoules, capsules, pills, tablets, powders, granules, solids, liquids, gels, bubbles, emulsions, sheets, Appropriate forms for using mist, sprays, etc. 1) Pharmaceuticals, 2) Quasi-drugs, 3) Topical or systemic skin cosmetics (for example, lotions, emulsions, creams, ointments, lotions, Basic cosmetics such as oils, packs, facial soaps and skin cleansing agents such as solid soap, liquid soap, hand wash, massage agents, cleansing agents, hair removal agents, hair removal agents, shaving treatments, aftershave lotions, pre-shows Makeup cosmetics such as lotion, shaving cream, foundation, lipstick, blusher, eye shadow, eyeliner, mascara, perfume, beauty nail, beauty nail (Namel, nail enamel remover, poultice, plaster, tape, sheet, patch, aerosol, etc.), 4) medicinal and / or cosmetic preparations applied to scalp and hair (eg shampoo) , Rinse agents, hair treatment agents, pre-hair treatment agents, permanent liquids, hair dyes, hair styling agents, hair styling agents, hair growth / hair restoration agents, poultices, plaster agents, tape agents, sheet agents, aerosol agents, etc.), 5) Bathing agent used in bath water, 6) Oral compositions such as dentifrices, mouthwashes, etc. 7) Other odor control agents and deodorants, antiperspirants, hygiene products, sanitary cotton, wet tissue, etc. Is mentioned.

  As a specific use of the whitening agent, it is mainly blended into an external preparation, and can be blended into the forms mentioned in the above-mentioned skin external preparation and skin whitening external preparation.

  If it is in the range which does not impair the effect of this invention, if it is in the range which does not impair the effect of this invention, it can mix | blend with the said skin external preparation, whitening skin external preparation, and a whitening agent, and can mix | blend the component which can be mix | blended below. Illustrate.

  (1) Various oils and fats: avocado oil, almond oil, fennel oil, egoma oil, olive oil, sesame oil, cacao oil, chamomile oil, safflower oil, shea fat, soybean oil, camellia oil, corn oil, rapeseed oil, castor Oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, palm oil, palm kernel oil, coconut oil, beef tallow, squalene, squalane, pristane or hydrogenated products of these oils (hardened oil, etc.), linseed oil, etc. .

  (2) Wax: beeswax, whale wax, lanolin, candelilla wax, montan wax, rice wax, etc.

  (3) Mineral oil: Liquid paraffin, petrolatum, paraffin, etc.

  (4) Fatty acids: lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, sodium oleate, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxystearic acid, undecylenic acid, Lanolin fatty acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid and the like.

  (5) Alcohols: ethanol, isopropanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterol, phenoxyethanol and the like.

  (6) Polyhydric alcohols: ethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, polyethylene glycol, propylene glycol, polypropylene glycol, 1,3-butylene glycol, glycerin, arabitol, xylitol, ribitol, sorbitol, mannitol, Maltitol etc.

  (7) Esters: isocetyl myristate, isostearyl myristate, 2-ethylhexyl palmitate, isocetyl palmitate, isostearyl palmitate, 2-ethylhexyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, ricinol Octyldodecyl acid, isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, phthalate Diethyl acid, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, diolein Propylene glycol, and the like.

  (8) Gums, sugars or water-soluble polymer compounds: xanthan gum, gum arabic, cablo gum, guar gum, karaya gum, quinseed, agar, casein, lactose, fructose, sucrose or esters thereof, trehalose or derivatives thereof, dextrin, gelatin , Pectin, starch, carrageenan, carboxymethyl chitin or chitosan, hydroxyalkyl (C2-C4) chitin or chitosan with addition of alkylene (C2-C4) oxide such as ethylene oxide, low molecular chitin or chitosan, chitosan salt, sulfate Chitin or chitosan, phosphorylated chitin or chitosan, alginic acid or salt thereof, hyaluronic acid or salt thereof, chondroitin sulfate or salt thereof, heparin, ethylcellulose, methylcellulose, carboxymethylcellulose, carboxyethylcellulose Sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate, polyalkylene oxide such as polyethylene oxide and polypropylene oxide, or cross-linking polymerization thereof Products, carboxyvinyl polymer, polyethyleneimine, etc.

  (9) Surfactant: Anionic surfactant (alkyl carboxylate, alkyl sulfonate, alkyl sulfate ester salt, alkyl phosphate ester salt, sodium laurate, potassium laurate, sodium palmitate, potassium palmitate, palm Oil fatty acid methyl taurine salt, N-caproyl methyl taurine salt, N-lauroyl methyl taurine salt, N-myristoyl methyl taurine salt, N-palmitoyl methyl taurine salt, N-stearoyl methyl taurine salt, N-oleoyl methyl taurine salt, N-cocoyl glutamate, N-lauroyl glutamate, N-myristoyl glutamate, N-palmitoyl glutamate, N-stearoyl glutamate, N-oleoyl glutamate, etc.), cationic surfactant (alkylamine) , Alkyl quaternary ammonium salt, stearyl trimethyl ammonium chloride, lauryl trimethyl ammonium chloride, alkyl trimethyl ammonium salt, distearyl dimethyl ammonium chloride), amphoteric surfactant (carboxylic acid type amphoteric surfactant (amino type, betaine type), sulfuric acid Ester type amphoteric surfactant, sulfonic acid type amphoteric surfactant, phosphate ester type amphoteric surfactant, 2-undecyl-N, N, N- (hydroxyethylcarboxymethyl) -2-imidazoline sodium, 2-cocoyl- 2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), nonionic surfactant (ether type nonionic surfactant, ether ester type nonionic surfactant, ester type nonionic surfactant, Block polymer type Surfactant, nitrogen-containing nonionic surfactant, glyceryl stearate, glyceryl stearate (SE), polyglyceryl-3 stearate distearate, glyceryl stearate citrate, polyglyceryl laurate-10, PEG-15 stearate Glyceryl, PEG-5 glyceryl stearate and di (citric acid / stearic acid) polyglyceryl-3, PEG-20 glyceryl triisostearate), other surfactants (natural surfactants, derivatives of protein hydrolysates, polymers Surfactants, surfactants containing titanium and silicon, and fluorocarbon surfactants).

  (10) Various vitamins: vitamin A group: retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), vitamin B group: thiamine hydrochloride, thiamine sulfate (vitamin B1) , Riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acid, nicotinic acids, pantothenic acids, biotins, choline, inositols, vitamin C group: vitamin C acid or derivatives thereof, vitamin D group : Ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), dihydrotaxosterol, vitamin E group: vitamin E or its derivatives, ubiquinones, vitamin K group: phytonadione (vitamin K1), menaquinone (vitamin K2), Me Nadione (vitamin K3), menadiol (vitamin K4), other essential fatty acids (vitamin F), carnitine, ferulic acid, γ-oryzanol, orotic acid, vitamin Ps (rutin, eriocitrin, hesperidin), vitamin U and the like.

  (11) Various amino acids: valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxy Amino acid derivatives such as lysine, arginine, ornithine, histidine, sulfates, phosphates, nitrates, citrates, or pyrrolidone carboxylic acids.

  (12) α-hydroxy acids: glycolic acid, citric acid, malic acid, tartaric acid, lactic acid, sodium lactate, etc.

  (13) Plant extracts: Ashitaba, Asunaro, Acerola, Asenyaku, Anise, Brassica, Avocado, Ama, Amacha, Achacharu, Amadokoro, Amaranth Us Hippochondriax), Aristolomeria (Yurizuisen), Altea, Arnica, Alpinia, Kumamadai, Aloe, Aloe Vera, Ansokkou, Strawberry, Fig, Ginkgo, Rice, Ibukikakuso, Nettle, Oolong Tea, Physalis, Uguiscagrau, Ikon , Udo or Shishido, Unyadegato, Ume, Unshumikan, Unboku, Estragon, Ezoukogi, Auren, Psyllium, Great Hawthorn or Prunus, barley, okra, ginseng or ginseng, Hypericum perforatum, scabbard hypericum, hypericum perforatum, periwinkle, onyokoro, tokoro, nagokoro, dutch mustard, olive, oregano, orange, cacao, cacao, oyster, carnation, oyster Weeping birch, gerbera, pumpkin, chamomile, roman chamomile, cam cam, color, guarana, carahoo, kawara mugwort, licorice, raspberry (Ezo strawberry, Dutch strawberry, shrimp strawberry, peach white strawberry, maple strawberry, European raspberry), kiwi, oleander, chrysanthemum ), Kidachi Aloe, Kumquat, Guava, Kudzu, Kumazasa, Clara, Cranberry, Chestnut, Grapefruit, Hikioko , Clove, Gumbai Tuna (Sekimei, Sekimeishi), Bay bay, Kenashi Sartorii rose, Gentiana, Gennoshouko, Kouseihakka, Koucha, Koganebana, Coco, Goshuyu, Goshostrawberry, Pepper, Cosmos, Coffee, Burdock, Sesame, Rice, Rice, Rice , Konjac, Comfrey, Yoshino cherry, Takane cherry, Kasumi cherry, Cherry, Pomegranate, Sasa, Sasanka, Sweet potato, Sugar cane, Sugar beet, Saffron, Pomegranate, Soap Aojiso, Chilemiso, Katamenjio, Janohige, Juzudama, Ginger, Ginger, White Clover, White Clover, White Vanilla, Watermelon, Honeysuckle, Ste A, Strawberry, Plum, Larch, Pepper, Prunus, Hawthorn, Dandelion, Horse Chestnut, Pear, Elderberry, Zeniai, Celery, Celery, Senkyu, Sendai, Senburi, Broad bean, Daio, Daikon, Daikon, Soybean, Daidai , Thyme, Periwinkle, Tachidokoro, Onion, Dahlia, Tanjin, Dandelion, Cherry, Tulip, Datura, Thrips, Camellia, Clover, Clover, Clover, Tengusa, Tencha, Ladybird, Togan, Toki, Tokachi, Tokajin, Tokajin Tounabena, corn, ginseng, dokudami, tomato, turkey, tormentilla, yam, yam, nagikada, jujube, d Zuku, elderberry, garlic, Neubara, Yarrow, Novara, Peach, Pineapple, Hibiscus (Bussouge, Furinbussouge, Roselle), Basil, Lotus, Parsley, Hadakagi, Batata, Hachiku, Hakka, Hathaha, Pai, Bananaha , Rose, anemone, pistachio, beet, cypress, castor, sunflower, belude oil, broad-leafed primrose, loquat, puer tea, sweet pepper, dandelion, dandelion, grape, beech, sycamore, blackberry, plum, blueberry, prunes, safflower , Spinach, spinach, hornbill, bowfish, spinach, physalis, physalis, bodaige, buttons, buttonpi, hop, jojoba, maoh, maca, macadamia natsu , Matatabi, Matsukasa, Pine, Mulberry, Quince, Malene, Mango, Mandarin, Mannentake, Miracle Fruit, Munchkin, Muguroji, Purple, Purple, Melissa, Melon, Mochinoki, Mokko, Peach, Moroheiya, Yaguru, Yasha, Yashabu Willow, bayberry, eucalyptus, saxifrage, yuzu, lily, yorogusa, mugwort, lime, rye, lacanca, raspberry, latania, rakkyo, shallot, lavender, longan, agave, ryokcha, apple, gentian, lubas, suabisimus Lettuce, red currant, red pitaya, lemon, lemongrass, forsythia, forsythia, forsythia, wintersweet, waxy palm, locon, loganberry , Rosemary, rose hips, wasabi, Watafujiutsugi, plant extract obtained from burnet, or the like, or extract obtained by culturing the cells of the plant,.

  (14) Seaweed extract: Seaweed [Green algae: Chlorella vulgaris, Chlorella pyrenoidosa, Chlorella ellipsoidia, Aonori (Usba aonori, Sugiaonori, Hiraaoori, Boaonori, Hosoeda Aonori), Anaaaosa (Aosa) algae] Kombu (Macombu, Risilibu, Hosocome, Mitsuishi Kombu), Wakame, Hirome, Aowakame, Giant Kelp (Macrocystis pilifera, Macrocystis integrifolia, Neocities Ruetkeana), Hijiki, Hibamata, Umiuchiwa, Kibago Noumiuchiwa, Akabaumiuchiwa, Konaumiuchiwa, Okinawauchiwa, Usukiuchiwa, Etukiumiuchiwa], seaweed [Red algae: Hijirimen, Maca (Tengusa), Hiraksa, Onyxa, Oaxa, Taobaxa, Yatabegusa, Yuukiri, Shimatengusa, Tosakanori, Togekirinsai, Amakusakirinsai, Giraffe , Seaweed extract obtained from culturing the cells of the seaweed or the like.

  (15) Animal extract: chicken crown extract, cow or pig, human placenta extract, cow or pig stomach, duodenum, intestine, spleen extract or its degradation product, cow or pig brain tissue extract, cow・ Collagen hydrolyzate (acid, alkali, enzyme, etc.) of pig or fish, collagen derivatives such as water-soluble collagen or acylated collagen, elastin or elastin hydrolyzate (acid, alkali, enzyme, etc.) or water of bovine or pig Sex elastin derivative, keratin and its degradation product or their derivatives, silk protein and its degradation product or their derivatives, pig or cow blood cell protein degradation product (globin peptide), cow or pig hemoglobin degradation product (hemin, hematin, Heme, protoheme, heme iron, etc.), milk, casein and its degradation products or their derivatives, skim milk powder and their degradation products or their derivatives, lactoferrin Alternatively, an animal extract obtained from a degradation product thereof, a chicken egg component, a fish meat degradation product, a nucleic acid-related substance (ribonucleic acid, deoxyribonucleic acid) or the like, or an extract obtained by culturing cells of the animal.

  (16) Microbial culture metabolites: yeast metabolites, yeast extract, bacterial metabolites, bacterial extract, mold or actinomycete metabolites, mold or actinomyces extract, natto metabolites, natto extract, rice fermentation Extract, rice bran (red rice bran, white rice bran) fermented extract, Euglena extract or decomposition product thereof or water-soluble derivative thereof, trehalose or derivative thereof, lactic acid fermentation product of raw milk or skim milk powder, lactic acid bacteria fermentation product of legumes, coconut palm plant Lactic acid bacteria fermented products.

  (17) Inorganic pigments: anhydrous silicic acid, magnesium silicate, talc, kaolin, bentonite, mica, titanium mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, calcium carbonate, magnesium carbonate, yellow iron oxide , Bengala, black iron oxide, Gunjo, chromium oxide, chromium hydroxide, carbon black, calamine, etc.

  (18) UV absorption / blocking agent: benzophenone derivative (2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid sodium, Dihydroxydimethoxybenzophenone, dihydroxydimethoxybenzophenone-sodium sulfonate, 2,4-dihydroxybenzophenone, tetrahydroxybenzophenone, etc.), paraaminobenzoic acid derivatives (paraaminobenzoic acid, ethyl paraaminobenzoate, glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate) Octyl paradimethylaminobenzoate), methoxycinnamate derivatives (ethyl paramethoxycinnamate, isopropyl paramethoxycinnamate, octyl paramethoxycinnamate) Til, 2-methoxyethyl paramethoxycinnamate, sodium paramethoxycinnamate, potassium paramethoxycinnamate, diparamethoxycinnamate mono-2-ethylhexanoate glyceryl, etc.), salicylic acid derivatives (octyl salicylate, phenyl salicylate, homomentyl salicylate, dipropylene glycol salicylate) , Ethylene glycol salicylate, myristyl salicylate, methyl salicylate, etc.), anthranilic acid derivatives (such as methyl anthranilate), urocanic acid derivatives (urocanic acid, ethyl urocanate etc.), coumarin derivatives, amino acid compounds, benzotriazole derivatives, tetrazole derivatives, Imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, furan derivatives, pyrone derivatives, nucleic acid derivatives, allantoin Conductor, nicotinic acid derivative, vitamin B6 derivative, umbelliferone, esculin, benzyl cinnamate, synoxate, oxybenzone, dioxybenzone, octabenzone, soribenzone, benzoresorcinol, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, neoheliopan, esca Rolls, zinc oxide, talc, kaolin, etc.

  (19) Whitening agent: paraaminobenzoic acid derivative, salicylic acid derivative, anthranilic acid derivative, coumarin derivative, amino acid compound, benzotriazole derivative, tetrazole derivative, imidazoline derivative, pyrimidine derivative, dioxane derivative, camphor derivative, furan derivative, pyrone derivative , Nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives, vitamin C or derivatives thereof (vitamin C phosphate magnesium salt, vitamin C glucoside, etc.), vitamin E or derivatives thereof, kojic acid or derivatives thereof, oxybenzone, benzophenone, arbutin, guaiazulene , Shikonin, baicalin, baicalein, berberine, placenta extract, ellagic acid, lucinol, hydroquinone, etc.

  (20) Astringents: succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc paraphenol sulfonate, potassium aluminum sulfate, resorcin, ferric chloride, tannic acid (including catechin compounds) and the like.

  (21) Antioxidants: hydroxytyrosol, parahydroxyanisole, propyl gallate, sesamol, sesamorin, gossypol, propolis, etc.

  (22) Anti-inflammatory agents: indomethacin, salicylic acid, sodium salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d-camphor, dl-camphor, hydrocortisone, guaiazulene, camazulene, chlorpheniramine maleate, glycyrrhizic acid or licorice extract.

  (23) Perfume: Musk, Civet, Castorium, Ambergris, Anise Essential Oil, Angelica Essential Oil, Ylang Ylang Essential Oil, Iris Essential Oil, Fennel Essential Oil, Orange Essential Oil, Kananga Essential Oil, Caraway Essential Oil, Cardamom Essential Oil, Guayak Wood Essential Oil, Cumin Essential Oil, Black Letter Essential Oil , Cinnamon essential oil, cinnamon essential oil, geranium essential oil, copaiba balsam essential oil, coriander essential oil, perilla essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, gingergrass essential oil, cedar essential oil, spearmint essential oil, western peppermint essential oil, dairy perfume essential oil, tuberose Essential oil, clove essential oil, orange flower essential oil, winter green essential oil, troubalsum essential oil, buttery essential oil, rose essential oil, palmarosa essential oil, cocoon essential oil, hiba essential oil, sandalwood essential oil, petit gren essential oil, bay essential oil, vetiva essential oil, bergamot essential oil, peruvian balsam Essential oil, boad rose essential oil, melamine essential oil, mandarin essential oil, eucalyptus essential oil, lime essential oil, lavender essential oil, linaloe essential oil, lemongrass essential oil, lemon essential oil, rosemary essential oil, Japanese mint essential oil, etc.

  (24) Dye and Colorant: Red Cabbage Dye, Red Rice Dye, Akane Dye, Anato Dye, Ikumi Dye, Turmeric Dye, Enju Dye, Krill Dye, Caramel Dye, Caramel, Gold, Silver, Gardenia Dye, Corn Dye, Onion Pigment, tamarind dye, spirulina dye, buckwheat whole plant dye, cherry dye, laver dye, hibiscus dye, grape juice dye, marigold dye, purple potato dye, purple yam dye, lac dye, rutin etc.

  In addition, dermatological extract, rotgenic acid or rotgenic acid salt (sodium rotogenate, calcium rotgenate, magnesium rotgenate, etc.) used in combination with the above ingredients, and a skin external preparation formulated with ingredients other than the above ingredients Expression of tyrosinase gene in pigment cells by whitening skin and skin cells, or by treatment with a composition containing bald gluten extract, rotgenic acid or rotgenic acid salt (sodium rotogenate, calcium rotogenate, magnesium rotogenate, etc.) To suppress melanin. As described above, the use of rotgenic acid or a salt thereof of the present invention can be provided as a skin care method for whitening or beauty, and a skin cell treatment method.

  Although the example of manufacture in the baked-kite extract used by this invention is explained in full detail below, the baked-kite extract of this invention is not limited to the following manufactured examples.

(Production Example 1) Bald potato extract A 3% 30% ethanol aqueous solution was added to 100 g of dried dolphins root, immersed for one week, and filtered to obtain 2.4 kg of baked kite extract.
(Production Example 2) Bald potato extract A 3% 50% aqueous methanol solution was added to 100 g of dried dolphins roots, soaked for one week and filtered to obtain 2.4 kg of baked kite extract.
(Production Example 3) Bald potato extract A 3% 70% aqueous ethanol solution was added to 100 g of dried dolphins roots, soaked for one week and filtered to obtain 2.4 kg of baked kite extract.

(Test 1) Suppression of Tyrosinase expression (bald potato extract)
After culturing B16 melanoma cells (RIKEN BRC) in a 60 mm dish with D-MEM (Wako) for 24 hours, the sample (the bald echten extract obtained in Production Examples 1 to 3 was adjusted to a final concentration of 1%. Control (comparative control) was added DMSO to a final concentration of 1%) and incubated for 1 hour, then α-MSH (SIGMA-ALDRICH) was added to a final concentration of 50 ng / mL. did. 24 hours after the addition of α-MSH, extraction was performed from cells using RNeasy Mini Kit (QIAGEN), and cDNA was synthesized using PrimeRNA RT reagent Kit (Takara Bio) using the obtained RNA as a template. Using this cDNA, the expression level of the Tyrosinase gene was measured by quantitative PCR.
In addition, SYBR Premix Ex Taq (Takara Bio Inc.) and Thermal Cycler Dice Real Time System (Takara Bio Inc.) were used for the quantitative PCR method. As an internal standard, the expression level of the RPS18 gene, which is a housekeeping gene, was quantified, and the relative expression level relative to RPS18 was calculated and used as the Tyrosinase gene expression level. Tyrosinase and RPS18 from Takara Bio Inc. were used as PCR primers.

(Test results)
It was found that the vulture extract obtained in Production Example 3 showed the highest Tyrosinase expression inhibitory effect.

(Test 2) Searching for active ingredients in baleen kite extract As a result of searching for components specifically contained in the baked kite extract of Production Example 3 using known analytical methods such as HPLC, LC-MS, NMR, It was found that rotogenic acid and ursolic acid were contained in a large amount in the vulture extract of Production Example 3.

  Examples of the production of rotgenic acid used in the present invention are described in detail below, but the rotogenic acid of the present invention is not limited to the following production examples, and in addition to extraction and purification from animals, plants and fungi, chemical synthesis and enzymatic reaction are used. Also included are those obtained for compounds obtained by any means of production.

(Production Example 4) Production of rotgenic acid According to a previous report (chem. Pharm. Bull. 43 (9) 1462-1465 (1995)), extraction was carried out 3 times with 10 L of methanol for 4 kg of vulture root, and then 1.3 kg After concentration, the mixture was partitioned with ethyl acetate-water, and the ethyl acetate layer was concentrated to obtain a solid content of 75 g. Further, 75 g of a solid content was dissolved in a mixed solution of ethyl acetate and hexane (ethyl acetate: hexane = 4: 1), and column purification was performed to obtain 7.5 g of a solid content. Thereafter, column purification was performed with chloroform / methanol mixture to obtain 110 mg of rotgenic acid.

(Test 3) LCMS analysis of rotgenic acid 0.89 mg of rotogenic acid obtained in Production Example 4 was dissolved in 1 ml of methanol, and LC / MS analysis was performed under the following conditions.
Analytical instrument: ACQUITY UPLC Class H (Waters)
Mass spectrometer: Xevo G2-S-QTof (Waters)
Photodiode array: (210-500nm)
Column: ACQUITY UPLC BEH C18 (50 × 2.1 mm ID, 2.1 μm)
Flow rate: 0.8 mL / min
Column temperature: 55 ° C
Solvent: Liquid A: 0.1% formic acid aqueous solution, liquid B: 0.1% formic acid acetonitrile solution gradient;
0 min;% A solution /% B solution = 95/5 → 6 min;% A solution /% B solution = 0/100
6 min;% A solution /% B solution = 0/100 → 7 min;% A solution /% B solution = 0/100

(Test results)
As shown in FIG. 2, the results were positive and m / z: 977.7, and negative and m / z: 487.2. Since the molecular weight of rotogenic acid was 488.7 (C ₃₀ H ₄₈ O ₅ ), the mass detected positive was [2M + H] ⁺ and the mass detected negative was [M−H] ⁻ .

(Test 4) NMR analysis of rotgenic acid 13.0 mg of rotogenic acid obtained in Production Example 4 was dissolved in C ₅ D ₅ N (600 μL), and ¹³ C-NMR measurement was performed. Further, the above rotogenic acid solution was diluted 6 times with C ₅ D ₅ N, and ¹ H-NMR measurement was also performed.

(Test results)
The results show the chemical shift values shown in Table 1, and are consistent with the values described in the previous report (Phytochemistry 28 (5) 1479-1482 (1989)). From the results of Test 3, the compound is rotgenic acid. Was identified.
¹³ CNMR properties of rotgenic acid

(Test 5) Preparation of salt of rotgenic acid Sodium rotogenate and calcium salt of rotgenic acid were prepared by a conventional method from the rotogenic acid obtained in the above production example.

(Test 6) Suppression of Tyrosinase expression (rotogenic acid, ursolic acid)
B16 melanoma cells (RIKEN BRC) were cultured in a 60 mm dish in D-MEM (Wako) for 24 hours, and then the samples (rotogenic acid and ursolic acid (INDOFINE Chemical) obtained in Production Example 4) were each at a final concentration of 0.8. Control (comparative control) was added with DMSO to a final concentration of 1%) and incubated for 1 hour, and then α-MSH (SIGMA-ALDRICH) was added at a final concentration of 50 ng / mL. It added so that it might become. 24 hours after the addition of α-MSH, extraction was performed from cells using RNeasy Mini Kit (QIAGEN), and cDNA was synthesized using PrimeRNA RT reagent Kit (Takara Bio) using the obtained RNA as a template. Using this cDNA, the expression level of the Tyrosinase gene was measured by quantitative PCR.
In addition, SYBR Premix Ex Taq (Takara Bio Inc.) and Thermal Cycler Dice Real Time System (Takara Bio Inc.) were used for the quantitative PCR method. As an internal standard, the expression level of the RPS18 gene, which is a housekeeping gene, was quantified, and the relative expression level relative to RPS18 was calculated and used as the Tyrosinase gene expression level. Tyrosinase and RPS18 from Takara Bio Inc. were used as PCR primers. Further, in order to confirm the concentration dependency of rotgenic acid, the same procedure was performed for final concentrations of 0.1 μM, 4 μM, and 10 μM.

(Test results)
The result is as shown in FIG. Under the condition that the expression of Tyrosinase gene was enhanced by the addition of α-MSH, ursolic acid did not show the gene expression-inhibiting effect. On the other hand, rotogenic acid was found to have a large inhibitory effect on Tyrosinase gene expression at a concentration of 0.8 μM. In addition, even when the condition of rotogenic acid was 0.1 μM, the inhibitory effect was slightly lower than that at a concentration of 0.8 μM. Also, the sodium salt and calcium salt of rotgenic acid obtained in Test 5 were added at a final concentration of 0.8 μM, and when Test 6 was performed, similar effects were obtained.

(Prescription example)
Although the formulation example using rotgenic acid or its salt is described below, it is not limited to the mixing | blending of this invention.

(Formulation example 1) Cream weight%
1. Rotogenic acid or its salt 0.001
2.4-tert-butyl-4'-methoxybenzoylmethane 0.30
3. Ascorbyl tetra-2-hexyldecanoate 1.0
4). Concentrated glycerin 3.0
5. Beeswax 1.5
6). Scrawan 8.0
7). Methylpolysiloxane 0.30
8). Decamethylcyclopentasiloxane 4.0
9. Cetyl palmitate 5.0
10. Trioctanoin 6.0
11. Behenyl alcohol 1.0
12 Stearic acid 2.5
13. Xanthan gum (2% aqueous solution) 10.0
14 Methylparaben adequate amount15. Propylparaben adequate amount 16. Phenoxyethanol 0.20
17. Purify water to 100

(Formulation Example 2) W / O Lotion Weight%
1. Rotogenic acid or its salt 0.001
2. L-Arginine 0.20
3. 1,3-butylene glycol 10.0
4). Meadow Home Oil 0.50
5. Jojoba oil 0.50
6). Carbomer 10.0
7). Tri 2-ethylhexanoic acid 19.0
8). Decaglyceryl penta 12-hydroxystearate 2.0
9. Methyl paraben Appropriate amount10. Purify water to 100

(Formulation example 3) Lotion weight%
1. Rotogenic acid or its salt 0.001
2. Citric acid 0.02
3. Na citrate 0.18
4). Pentylene glycol 3.0
5. Diethoxyethyl succinate 15.0
6). Purify water to 100

(Formulation example 4) Beauty liquid weight%
1. Rotogenic acid or its salt 0.001
2. Dl-α-tocopherol acetate 0.10
3. Panthenol 0.10
4). L-Arginine 0.30
5. Water-soluble collagen 0.10
6). Decamacademia nut fatty acid polyglyceryl-10 0.20
7). Sodium hyaluronate solution 0.50
8). Polyglyceryl monooleate 1.50
9.1,3-Butylene glycol 3.00
10. Maltose (75% aqueous solution) 1.00
11. Glycerin 4.00
12 Carboxyvinyl polymer 11.25
13. Edetate tetrasodium 0.10
14 Xanthan gum (2% aqueous solution) 3.75
15. Methylparaben adequate amount 16. Phenoxyethanol 0.20
17. Purify water to 100

(Formulation Example 5) Milk weight%
1. Rotogenic acid or its salt 0.001
2. Hydroxypropyl starch phosphate 2.0
3. Cetostearyl rucol 2.0
4). Sorbitan stearate 2.0
5. PPG-15 stearyl 4.0
6). Trioctanoin 5.0
7). Tricaprylglycerin 5.0
8). Dimethicone 1.0
9. Glycerin 4.0
10. Phenoxyethanol 0.20
11. Methylparaben adequate amount 12. Purify water to 100

(Formulation example 6) Whitening cream weight%
1. Rotogenic acid or its salt 0.001
2. Hexaglyceryl condensed ricinoleate 1.5
3. Purified hydrogenated soybean phospholipid 0.30
4.1.3-Butylene glycol 7.0
5. Sodium alginate 20.0
6). Diglyceryl monoisostearate 1.5
7.2 Cetyl 2-ethylhexanoate 7.0
8). Methylphenylpolysiloxane 5.0
9. Glycerin 8.0
10. Methylparaben appropriate amount11. Vegetable ceramide (Yuzu) 0.5
12 Purify water to 100

(Formulation example 7) Massage cream Weight%
1. Rotogenic acid or its salt 0.001
2. Hydroxide Na 1.0
3. Carbomer 20.0
4). Mannan 8.0
5. Castor oil 3.0
6). Diphenylmethicone 0.05
7). Cetearyl alcohol 1.5
8). Phenyltrimethicone 4.5
9. Ceramide 0.3
10. BG 5.0
11. Glycosyl trehalose 8.0
12 Glycerin 3.0
13. Methylparaben 0.20
14 Purify water to 100

(Formulation Example 8) Peel-off pack Weight%
1. Rotogenic acid or its salt 0.001
2. Polyvinyl alcohol 15.0
3. Hydroxypropyl cellulose 1.0
4.1.3-Butylene glycol 5.0
5. Chitosan PCA 20.0
6). Methylparaben 0.20
7). Ethanol 10.0
8). Purify water to 100

(Formulation example 9) After shave lotion% by weight
1. Rotogenic acid or its salt 0.001
2.1-Menthol 0.20
3. Triethylhexyl citrate 1.0
4). Sorbitol 5.0
5. Triethanolamine 0.10
6). Glycerin fatty acid ester mixture 0.50
7). Hydroxypropyl methylcellulose 2.0
8). Glycerin 3.0
9. Carbomer 0.50
10. Castor oil 1.0
11. Methylparaben adequate amount 12. Purify water to 100

(Prescription Example 10) Liquid Foundation Weight%
1. Rotogenic acid or its salt 0.001
2. Polyglyceryl pentaisostearate-10 1.5
3. Triethylhexyl citrate 6.0
4). Sodium glutamate 0.50
5. Scrawan 3.0
6). Glycerin 5.0
7). Methyl polysiloxane 0.50
8). Decamethylcyclopentasiloxane 10.0
9. Pigment 15.0
10. Methylparaben appropriate amount11. Purify water to 100

(Formulation Example 11) Lipstick Weight%
1. Rotogenic acid or its salt 0.001
2. Hydrogenated Olive Stearyl Esters 3.0
3. Isotridecyl isononanoate 5.0
4). Olefin oligomer 14.0
5. Polyglyceryl-2 triisostearate 14.7
6). Hydrogenated polyisobutene 18.0
7). Tocopherol 0.10
8). Polyethylene 5.0
9. Candelilla Row 6.5
10. Hydrogenated pentaerythritol rosinate 12.0
11. Hydroxyapatite 1.0
12 Microcrystalline wax 3.0
13. Silylated silica 0.50
14 Red 202, polyglyceryl triisostearate-2 0.75
15. Titanium oxide, Al hydroxide
Polyglyceryl-2 triisostearate 0.90
16. Iron oxide, polyglyceryl-2 triisostearate-2.20
17. Blue 1, polyglyceryl-2 triisostearate 0.15
18. Titanium oxide, mica 5.0
19. Propylparaben 0.10
20. Isododecane 9.0

(Prescription Example 12) Eyeshadow Weight%
1. Rotogenic acid or its salt 0.001
2. Firing mica 10.0
3. Pearl pigment 50.0
4). Lanolin 2.0
5. Sorbitan Sesquio Elate 2.0
6). Talc 3.0
7). Liquid paraffin 8.0
8). Pigment 5.0
9. Perfume appropriate amount10. Preservative appropriate amount

(Formulation Example 13) Cleansing oil wt%
1. Rotogenic acid or its salt 0.001
2. Diethoxyethyl succinate 3.0
3. Pentylene glycol 3.0
4). 4. Sodium citrate appropriate amount Polyglyceryl triisostearate-2 3.0
6). PEG-10 glyceryl diisostearate 5.0
7). PEG-30 triisostearate 15.0
8). Purified water 1.5
9. Total amount of neopentyl glycol diisononanoate to 100

(Formulation Example 14) Shampoo Weight%
1. Rotogenic acid or its salt 0.001
2. Guar hydroxypropyltrimonium chloride 0.10
3. Hydrolyzed collagen 0.20
4). PCA 2.0
5. Cocoyl glutamic acid K 2.0
6). Cocamide DEA 3.0
7). Lauramidopropylbetaine, water, Na chloride 4.0
8). Lauryl sulfate TEA 22.0
9. Fragrance 0.10
10. Methylparaben appropriate amount11. Purify water to 100

(Formulation Example 15) Conditioning shampoo Weight%
1. Rotogenic acid or its salt 0.001
2. Citric acid 0.10
3. Polyquaternium-10 0.15
4). Horse oil 1.0
5. PCA-Na 1.0
6). PEG-40 hydrogenated castor oil 2.50
7). Distearic acid PEG-150 1.0
8). Cocamide DEA 4.0
9. Cocamidopropyl betaine 8.0
10. Lauryl sulfate TEA 9.0
11. Laureth sulfate Na 27.0
12 Fragrance 0.1
13. Methylparaben adequate amount14. Purify water to 100

(Formulation Example 16) Hair wax Weight%
1. Rotogenic acid or its salt 0.001
2. Dibutylethylhexanoyl 3.0
3. Pentylene glycol 3.0
4). Ethyl hexyl hydroxystearate 5.0
5. Polyglyceryl isostearate-10 1.50
6). Glyceryl stearate 2.0
7). (Polyglyceryl-2 isostearate
/ Dimerlinoleic acid) copolymer 4.50
8). Hydroxide K 0.08
9. Dimethicone 2.0
10. Carbomer 0.30
11. Purify water to 100

(Formulation Example 17) Acid hair dye Weight%
1. Rotogenic acid or its salt 0.001
2. Dye 0.50
3. Glycolic acid 5.0
4). Bisethoxydiglycol succinate 5.0
5. Hydroxyethyl cellulose 2.0
6). Ethanol 15.0
7). Purify water to 100

(Formulation example 18) Hair rinse weight%
1. Rotogenic acid or its salt 0.001
2. Copper chlorofin Na 0.10
3. Hydrolyzed collagen 0.50
4). Steartrimonium chloride 8.0
5. Brown algae extract 0.20
6). Dextrin palmitate 0.20
7). Dipentaerystil 1.0
8). Tanakura clay 1.0
9. Mineral oil 3.0
10. Cetanol 5.0
11. Ores-8 2.0
12 Citric acid 0.10
13. Fragrance 0.10
14 Methylparaben adequate amount15. Propylparaben adequate amount 16. Dimethicone 0.50
17. Butylene glycol 6.0
18. Purify water to 100

(Prescription Example 19) Hair Treatment Weight%
1. Rotogenic acid or its salt 0.001
2. Birch extract 0.50
3. Sage extract 0.50
4). Steartrimonium chloride 1.50
5. Disteardimonium chloride 1.50
6). Hydrolyzed collagen 2.0
7). Hydroxyethyl cellulose 0.10
8). Steerless-15 1.0
9. Behenyl alcohol 2.0
10. Cetanol 3.0
11. Suritil 1.0
12 Methylparaben appropriate amount13. Propylparaben adequate amount14. Dipropylene glycol 5.0
15. Purify water to 100

(Prescription Example 20) Hair Tonic Weight%
1. Rotogenic acid or its salt 0.001
2.1-Menthol 0.05
3. PEG phytosterol 1.0
4). dl-α-tocopherol 0.10
5. Hinokitiol 0.05
6). Ethanol 30.0
7). Purify water to 100

(Prescription Example 21) Shaving cream% by weight
1. Rotogenic acid or its salt 0.001
2. TEA 3.0
3. Trioctane 2.0
4). Mineral oil 4.0
5. Xanthan gum 0.20
6). Dimethicone 0.50
7). Polysorbate 80 2.0
8). Stearic acid 18.0
9. Fragrance 0.10
10. Methylparaben appropriate amount11. Butylene glycol 8.0
12 Purify water to 100

(Formulation Example 22) Sunscreen cream% by weight
1. Rotogenic acid or its salt 0.001
2. Arbutin 3.0
3. Neopentyl glycol dicaprate 2.0
4). Phytosteryl hydroxystearate 4.0
5. Xanthan gum 0.15
6). Hyaluronic acid Na 1.25
7). Scrawan 8.0
8). Dimethicone 0.5
9. (Dimethicone / vinyl dimethicone) Cross polymer 1.5
10. Cyclopentasiloxane 5.0
11. Stearic acid 0.25
12 PEG-20 glyceryl stearate 1.0
13. Sorbitan stearate 1.0
14 Glycerin stearate 1.0
15. Cetearyl alcohol 1.0
16. Etidronic acid 5.0
17. Methylparaben 0.2
18. Propylparaben 0.05
19. Glycerin 2.0
20. Butylene glycol 5.0
21. Purify water to 100

(Formulation example 23) Body shampoo% by weight
1. Rotogenic acid or its salt 0.001
2. Scrawan 0.50
3. Glycol distearate 2.0
4). Hydroxide K 4.70
5. Stearic acid 3.0
6). Myristic acid 4.0
7). Lauric acid 9.0
8). Lauramidopropyl betaine 25.0
9. EDTA-2Na 0.1
10. Fragrance 0.2
11. Methylparaben 0.3
12 Propylene glycol 11.0
13. Purify water to 100

(Formulation example 24) Hand soap Weight%
1. Rotogenic acid or its salt 0.001
2. Potash stone base 10.0
3. Distearic acid PEG-150 2.0
4). Cocamide DEA 3.0
5. Lauryl sulfate TEA 40.0
6). EDTA-2Na 0.1
7). Citric acid 0.5
8). Methylparaben 0.1
9. Glycerin 8.0
10. Purify water to 100

(Formulation Example 25) Liquid soap weight%
1. Rotogenic acid or its salt 0.001
2. Dioleic acid PEG-120 methyl glucose 1.5
3. Polyoctanium-6 1.0
4). Olivem 300 2.0
5. Olivem 400 8.75
6). Lauramidopropyl betaine 6.0
7). Capryloyl glutamate Na 10.0
8). Cocamide DEA 1.0
9. Fragrance 0.1
10. Methylparaben appropriate amount11. Purify water to 100

(Formulation Example 26) Face Wash Weight%
1. Rotogenic acid or its salt 0.001
2. Tocopherol 0.10
3. Glycosyl trehalose 7.0
4). PEG-75 3.0
5. Glycol distearate 2.0
6). Distearic acid PEG-150 6.0
7). Lauramide DEA 4.0
8). Hydroxide K 6.30
9. Lauramidopropyl betaine 15.0
10. Stearic acid 7.0
11. Palmitic acid 9.0
12 Myristic acid 14.0
13. Methylparaben adequate amount14. Purify water to 100

(Formulation example 27) Bath agent weight%
1. Rotogenic acid or its salt 0.001
2. Sodium bicarbonate 39.0
3. Fragrance 1.0
4). Dextrin-coated titanium oxide 9.0
5. 100% dry sodium sulfate

(Prescription Example 28) Acne Cream Weight%
1. Rotogenic acid or its salt 0.001
2. Placenta extract 1.0
3. Hydrolyzed yeast, 10.0
4). Arginine 0.80
5. Scrawan 5.0
6). Dimethicone 0.20
7). Phenyltrimethicone 1.0
8). Glyceryl stearate 0.50
9. Stearic acid 1.0
10. Polysorbate 60 1.5
11. PEG-30 3.0
12 Carbomer 25.0
13. Methylparaben adequate amount14. Propylparaben adequate amount15. Butylene glycol 8.0
16. Purify water to 100

(Prescription Example 29) Toothpaste Weight%
1. Rotogenic acid or its salt 0.001
2. Tranexamic acid 0.05
3. Sodium monofluorophosphate 0.73
4). Ascorbic acid-2-phosphate magnesium 0.30
5. Precipitated silica 15.0
6). Sodium chloride 5.0
7). Sodium hydroxide 0.25
8). Sodium lauryl sulfate 1.50
9. Sodium carboxymethylcellulose 0.80
10. Carrageenan 0.60
11. Thickening silica 4.0
12 Citric acid 0.10
13. Saccharin sodium 0.18
14 Fragrance 1.30
15.70% sorbite solution 45.0
16. Propylene glycol 3.0
17. Purify water to 100

(Formulation Example 30) Eyelash serum for weight%
1. Rotogenic acid or its salt 0.001
2. Glucosyl hesperidin 0.10
3. Hydroxyethyl cellulose 0.50
4). Carboxyvinyl polymer 1.0
5. Edetate trisodium 0.02
6). Triethanolamine 0.20
7). Methylparaben 0.20
8). Ethanol 5.0
9.1,3-Butylene glycol 5.0
10. Purify water to 100

(Prescription Example 31) Eyebrow, Eyelash Hair Growth Gel Weight%
1. Rotogenic acid or its salt 0.001
2. EO-modified silicone 1.0
3. Amphoteric polymer 1.0
4). Carboxyvinyl polymer 0.5
5. Decaglycerin monoisostearate 4.0
6). POE (30) isocetyl ether 0.5
7). Methylparaben 0.1
8). Sodium bisulfite 0.05
9. Edetate disodium 0.05
10. Fragrance 0.5
11. Triethanolamine appropriate amount 12. Ethanol 10.0
13. Purify water to 100

(Prescription Example 32) Antiperspirant Spray Weight%
1. Rotogenic acid or its salt 0.001
2. Anhydrous ethyl alcohol 46.50
3. 1,3-butylene glycol 1.30
4). Isopropyl myristate 1.0
5. Fragrance 0.20
6). LPG appropriate amount

(Test 7) Usability test Rotogenic acid, sodium lauryl sulfate, and purified water were dispersed at a weight ratio of 30: 3: 67 and wet-pulverized with a high-pressure homogenizer. Grinding conditions were performed at a processing pressure of 200 MPa and a processing frequency of 80 times. Based on Formulation Example 6, the resulting suspension was used to prepare whitening creams of formulas a to c3 shown in Table 2 below. The panel was evaluated for use feeling. The evaluation items for the feeling of use are the spread at the time of application and the smoothness after the application.

(Test results)
As a result, as shown in Table 3 below, the average score is 3 or more when the mass concentration of rotgenic acid is 1% or 5%, but the average score is 2 or less when 7%, and the mass concentration of rotgenic acid in the external preparation is 5 % Or less, it is predicted that an external preparation with good usability will be obtained.
(Score basis)
5: Very good usability 4: Good usability 3: Normal usability 2: Very good usability 1: No good usability

(Test 8) Use Effect Test Based on Formulation Example 6 of the present invention, whitening creams of Formulas A to D4 shown in Table 4 below were prepared. For 20 adult men and women, the prepared whitening cream was applied to the face twice a day, and a one month use test was conducted. In addition, the test subject was divided into five persons, and the spots and pigmentation were evaluated as compared with before use.

(Test results)
As a result, as shown in Table 5 below, it was confirmed that the formulation containing rotgenic acid was higher than the control product, and in particular, the formulation B containing 0.1% was higher than the other formulations.
Effective: Blemish and pigmentation improved compared to before use.
Slightly effective: Blemishes and pigmentation were slightly improved than before use.
Invalid: No change before use.

Claims (2)

A skin whitening external preparation containing rotgenic acid or a salt thereof as an active ingredient for whitening in an amount of 0.00004 to 5% by weight. A whitening agent containing 0.00004 to 5% by weight of rotgenic acid or a salt thereof as an active ingredient for whitening .