JP2019038754A - Skin external preparation - Google Patents

Abstract

To provide a novel whitening component, a skin external preparation containing the novel whitening component, a whitening skin external preparation, and a whitening agent.SOLUTION: In order to find a novel whitening component, as a result of a test for a number of plant extracts which have not been studied yet of their whitening effects, Rotsugenin acid contained in Morinda officinalis extracts of Rubiaceae plants have a high whitening effect. Accordingly, the present inventors provide a skin external preparation, a whitening skin external preparation, and a whitening agent containing the Rotsugenin acid.SELECTED DRAWING: None

Description

  The present invention relates to an external preparation for skin, an external preparation for skin lightening, and a skin lightening agent.

  In cosmetic terms, pigmentation of stains on the skin, buckwheat and the like is regarded as a problem, and it has been proposed to incorporate components such as arbutin, ascorbic acid derivatives, kojic acid and the like which suppress pigmentation into skin cosmetics. However, ultraviolet rays reaching the epidermis tend to increase year by year due to air pollution and ozone layer depletion, and there is a need for novel components effective for preventing and improving pigmentation corresponding thereto. (Patent documents 1 to 3)

  Therefore, although it has been reported that, for example, polyphenol derived from walnut has shown a whitening effect as a component to be changed to the conventional whitening component, an effect superior to that of the conventional whitening component could not be confirmed (Patent Document 4).

JP-A-9-20610 JP-A-4-182492 Japanese Patent Application Laid-Open No. 2-200622 Japanese Patent Application Publication No. 2008-81408

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

  As a result of conducting tests on a large number of plant extracts whose whitening effect has not yet been examined in order to find new whitening ingredients, a whitening effect was found in the rhubarb extract of rhubarbs, and further included Found a high whitening effect on rotogenic acid. Therefore, the present inventors provide an external preparation for skin containing rotogenic acid, an external preparation for whitening, and a whitening agent.

That is, the present invention includes the following items.
[Item 1] An external preparation for skin containing rottenic acid or a salt thereof.
[Item 2] A skin whitening preparation for external use, which contains rottenic acid or a salt thereof.
[Item 3] A skin-whitening agent containing rottenic acid or a salt thereof.
[Item 4] A skin external preparation containing a hage quitten extract which essentially comprises rotogenic acid or a salt thereof.
[Item 5] A skin lightening external preparation for skin whitening which comprises a hage quitten extract which essentially comprises rotogenic acid or a salt thereof.
[Item 6] A skin-whitening agent comprising a hage quitten extract which essentially comprises rotogenic acid or a salt thereof.

  According to the present invention, it is possible to provide a skin external preparation, a skin external preparation for whitening, and a whitening agent derived from plants that have a safe and excellent whitening effect.

LC / MS chart of rotsevenic acid It is a figure which shows the tyrosinase gene expression suppression effect | action of a rotugenic acid.

  In addition, the root of a plant of the family Rubiaceae (Rubiaceae): Hagekitene (scientific name: Morinda officinalis) is used as "Hagekitene" used in the present invention.

  It is preferable to use a root of a hazukiten for use in the present invention, but it is also possible to use one or more species selected from flowers, leaves, seeds and the like. Further, the extract can be obtained by adding a solvent to the pressing liquid and / or residue obtained after the pressing treatment, in addition to those obtained by direct extraction from these various extraction sites using a solvent. Those are also included in the scope of the definition of the extract in the present invention.

  As an extraction solvent for obtaining the hage quitene extract used in the present invention, an organic solvent such as methanol, ethanol or butylene glycol is preferable, but the solvent can be easily removed after extraction when the inclusion of the solvent is not preferable depending on the use. It is also possible to carry out extraction using a highly volatile solvent and dissolve it in water or butylene glycol after solvent removal. Also, appropriate extraction may be performed.

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

  After extraction with a solvent, it is also possible to appropriately carry out a purification operation, and the purification operation may be performed using an acid (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, organic acid, etc.) or an alkali (water Decomposition by addition of sodium oxide, calcium hydroxide, ammonia etc., fermentation or metabolic conversion by microorganisms, adsorption of components by ion exchange resin, activated carbon, diatomaceous earth etc., various separation modes (ion exchange, hydrophilic adsorption, hydrophobic adsorption) , Size exclusion, ligand exchange, affinity etc.), filtration using filter paper, membrane filter, ultrafiltration membrane etc., pressure or reduced pressure, heating or cooling, drying, pH Adjustment, deodorization, decolorization, long-term stationary storage, etc. can be illustrated, and it is possible to perform processing which selected these arbitrarily and combined.

The compound in the form of a rothgenic acid and / or a pharmaceutically acceptable salt represented by the following chemical structural formula (Chem. 1) used in the present invention can be obtained from plants, animals, cells, etc. by extraction, synthesis, etc. In the present invention, since the hagekiten extract in the present invention contains a lot of rothgenic acid, purification may be performed using a column etc. therefrom. For example, sodium, potassium, calcium, monovalent or divalent or higher inorganic salts such as magnesium and zinc, organic salts such as organic amines and basic amino acids, or salts formed by a combination thereof can be mentioned.

  In the preparation of the skin external preparation of the present invention, the skin external preparation for whitening, and the whitening agent, the form of the hagekitene extract used and the salt of rotsugenic acid or rotsugenic acid may be liquid, solid, powder, paste, etc. The shape may be any shape, and an optimum shape can be arbitrarily selected in practicing the present invention.

  There is no particular limitation as to the content of the hazekten extract in the various compositions of the present invention, as long as it can be confirmed to suppress the expression of tyrosinase, but generally 0.01 mg / g to 200 mg / g (denominator) Represents the weight of the preparation). Preferably it is in the range of 0.1 mg / g to 20 mg / g, and most preferably the hazekten extract is 200 μg / g to 10 mg / g. There are no particular limitations on the rotogenic acid and / or pharmaceutically acceptable salt as long as it can be confirmed to suppress tyrosinase expression, but it is preferably 0.00004 to 5% by weight. This is because the inhibitory effect of 0.00004% by weight (about 0.8 μM) was higher than that of Tyrosinase gene expression on B16 melanoma cells at 0.000005% by weight (about 0.1 μM) of rotogenic acid, and It is derived from the fact that the external use agent had a better feeling of use when 5% by weight was blended as compared to when 7% by weight of rotogenic acid was blended.

  The external preparation for skin according to the present invention, the external preparation for skin lightening, and the skin lightening agent are optional, and may be ampoule, capsule, powder, granule, pill, tablet, solid, liquid, gel, bubbles It may be in the form of emulsion, cream, cream, ointment, sheet, mousse, powder dispersion, multilayer, aerosol or the like.

  Specific external skin preparations and skin external preparations for whitening (including preparations for use for animals) include ampules, capsules, pills, tablets, powders, granules, solid, liquid, gel, bubbles, emulsions, sheets, 1) Pharmaceutical products in a suitable form for use such as mist, spray, 2) quasi-drugs, 3) skin cosmetics for topical use or whole body use (for example, lotion, milk, cream, ointment, lotion, Oil, basic cosmetics such as pack, solid soap, liquid soap, hand wash and skin cleanser such as hand wash, massage agent, cleansing agent, hair remover, hair remover, shaving agent, after shave lotion, pre-show Make-up cosmetics such as blotion, shaving cream, foundation, lipstick, blusher, eye shadow, eyeliner, mascara, perfumes, nail polish, beauty nail Namel, nail polish remover, patch, plaster, tape, sheet, patch, aerosol etc.) 4) Medicinal and / or cosmetic preparations to be applied to scalp and hair (eg, shampoo) , Rinse agent, hair treatment agent, pre-hair treatment agent, permanent solution, hair dye, hair setting agent, hair tonic agent, hair growth and nourishing agent, cataplasm, plaster, tape agent, sheet agent, aerosol agent etc.) 5) Bath additives used in bath water, 6) Oral compositions such as dentifrices and mouthwashes, 7) Others, anti-odor and deodorant, antiperspirants, hygiene products, sanitary cottons, wet tissues etc. Can be mentioned.

  A specific use of the whitening agent is mainly compounding to an external preparation, and it can be mixed into the forms mentioned above for the skin external preparation and the skin external preparation for whitening.

  The external skin preparation, skin external preparation for whitening, and whitening agent may be any component that is generally used for external preparations, as long as the effects of the present invention are not impaired. I will illustrate.

  (1) Various fats and oils: avocado oil, almond oil, bilberry oil, sesame oil, olive oil, sesame oil, cacao butter, chamomile oil, safflower oil, shea butter, soybean oil, camellia oil, corn oil, rapeseed oil, castor oil 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 and fats (hardened oil etc.), linseed oil etc. .

  (2) Waxes: beeswax, bees wax, lanolin, candelilla wax, montan wax, rice wax and the like.

  (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 et al.

  (7) Esters: Isocetyl myristate, isostearyl myristate, 2-ethylhexyl palmitate, isocetyl palmitate, isostearyl palmitate, 2-ethylhexyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, ricinole Octodecyl dodecyl, isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyl dodecyl myristate, hexyl decyl dimethyl octanoate, cetyl lactate, myristyl lactate, phthalate Acid diethyl, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, diolein Propylene glycol, and the like.

  (8) Gums, saccharides or water-soluble polymer compounds: xanthan gum, gum arabic, cabro 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 to C4) chitin or chitosan to which alkylene (C2 to C4) oxide such as ethylene oxide is added, low molecular chitin or chitosan, chitosan salt, sulfated Chitin or chitosan, phosphorylated chitin or chitosan, alginic acid or a salt thereof, hyaluronic acid or a salt thereof, chondroitin sulfate or a salt thereof, heparin, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose Sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate, polyalkylene oxides such as polyethylene oxide and polypropylene oxide, or cross-linked polymerization thereof , Carboxyvinyl polymers, polyethyleneimine etc.

  (9) Surfactants: anionic surfactants (alkyl carboxylates, alkyl sulfonates, alkyl sulfates, alkyl phosphates, sodium laurate, potassium laurate, sodium palmitate, potassium palmitate, coconut 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 surfactants (alkylamines) 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, phosphoric acid ester type amphoteric surfactant, 2-undecyl-N, N, N- (hydroxyethyl carboxymethyl) -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 non Surfactant, nitrogen-containing nonionic surfactant, glyceryl stearate, glyceryl stearate (SE), polyglyceryl distearate-3 methyl glucose, glyceryl citrate stearate, 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, fluorocarbon surfactants) and the like.

  (10) Various vitamins: vitamin A: retinol, retinal (vitamin A1), dehydroretinal (vitamin A 2), carotene, lycopene (provitamin A), vitamin B: thiamine hydrochloride, thiamine sulfate (vitamin B1) , Riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folates, 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), dihydrotachysterol, vitamin E group: vitamin E or derivatives thereof, 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 Lysine, arginine, ornithine, histidine etc. and their sulfates, phosphates, nitrates, citrates or amino acid derivatives such as pyrrolidone carboxylic acid etc.

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

  (13) Plant extracts: Ashitara, Aserola, Asenyak, Anise, Brassica, Avocado, Ama, Amacha, Amacha, Amacho, Amaranth, Amaranth (Himyu, Hagegai, Himogai Tow, Sennin Kok, Sugimo Rei, Toshio Goigaito, Aogai touri, Amarisu Amararan, Us-Hipochondoriax), Aristromelia (Auris thaliana), Altea, Alnica, Alpinia, Aquila, Aloe, Aloe, Aloe Vera, Ansococco, Strawberry, Fig, Ginkgo, Rice, Persimmon, Nettle, Oolong Tea, Fleur-de-Sac, Gras, Turmeric, Usvenia oi , Udo or Shishiodo, Una degato, Ume, Satsuma mandarin orange, Umboku, Estragon, Eleuro sorghum, Oulen, Plantain, or Ginseng, barley, okra, carrots or spinach carrots, spinach, spinach, spinach, spinach, spinach, spinach, spinach, spinach, olive, oregano, orange, silkworm, cacao, oyster, carnation, birch, Birch, gerbera, pumpkin, chamomile, camomile, camphor, color, galana, calahoeo, kawara yomogi, licorice, licorice, raspberry (Ezo strawberry, Dutch strawberry, Shrimp strawberry, Nawashiro strawberry, Momiji strawberry, European raspberry), Kiwi, Kikyo, Kikusui ), Yellowtail, kumquat, guava, kudzu, kumazasa, Clara, cranberry, chestnut, grapefruit, pomegranate , Clove, Gunbainazuna (Sekimei, Sekimeishi), Geckeage, Kenashi sarutiribara, Gentiana, Gennoshoko, Kosuihaika, Kocha, Koganebana, Kogoushi, Goshoyu, Goshoyu, Pepper, Cosmos, Coffee, Burdock, Sesame, Matsubusa, Wheat, Rice, Rice porridge , Konjak, Comfrey, Somei Yoshino, Takamazakura, Cherry, Pomegranate, Sasa, Sasanuka, Sweet potato, Sugar cane, Sugar cane, Sugar radish, Sabon, Sabong, Sabino, Salvia, Sangyu, Sangsho, Shiioki, Shiitake, Shikamame, Jikitalis, Shiso, Aojiji, Chirimenjiso, Catamenso, Janohite, Juzudama, Ginger, Shoub, White clover, White azuki bean, White clover, Watermelon, Watermelon, Steal A, Strawberry, Smomo, Larch, Lentinus edulis, Gill, Cinnamomella, C. japonicus, C. p. , Thyme, Sperm, Persimmon, Onion, Dahlia, Tanjin, Dandelion, Cherry, Tulip, Persimmon, Thistle, Persimmon, Persimmon, Persimmon, Tuscusa, Tuscusa, Tuscusa, Tenthusa, Tencha, Teni-yuyak, Tougan, Pepper, Toi-Kan, Toi-Kansenka, Toi-saika Tounabena, corn, chrysanthemum, dokdami, tomato, toukyuri, torumenthira, nagaimo, yamanoimo, naguiikada, jujube Zuk, elderberry, garlic, neurala, yarrow, nobara, nomomo, pineapple, hibiscus (bush serge, リ ン リ ン ブ ッ ブ ッ バ ジ ル, rosell), basil, lotus, parsley, snail, moth, beech, peppermint, bald eagle, banana, hummingbird, banana hana, hamanas, hamamelis , Rose, Hevea, Pistachio, Beet, Hinoki, Castor, Sunflower, Belowed Dawley, Beech, Poial tea, Pooula tea, Fuyu Kazura, Hydrangea, Pheasant dandelion, Grape, Beech, Nervosa, Blackberry, Plum, Blueberry, Prune, Safflower, Benkeisou , Borax, borax, borax, buffalo, spinach, bromeliad, batterfish, button, button peony, hop, jojoba, maow, maca, macadamian , Matatabi, pine casa, pine, mulberry, quince, malene, mandarin, manganine, mananchi, miracle fruit, mukunoki, mukuroji, murasaki, murasaki xib, melissa, melon, mochinoki, mokko, momo, hemoya, cornflower, yacon, yashabushi, yatsude, Willow, bayberry, eucalyptus, yukinoshita, lily, lilies, mugwort, lime, rye, raccoon, raspberry, latania, raccoon, shallots, lavender, longan, rhubarb, rhubarb, ryokucha, apple, gentian, rubas, suabisimus, luri thomasami, Lettuce, red currant, red pitaya, lemon, lemongrass, forsythia, Chinese forsythia, Chinese forsythia, lotus root, locust bean, wax 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 pyrynoidosa, Chlorella ellipsoidea, Aoroni (usbaa nori, Susiaonori, Hirao Aonori, Bowa Aonori, Hosoe aonaori), Anaaosa (Aosa), seaweed [brown algae: Seaweed (Macomb, lychee ibu, Hosome kombu, mitsuishi kombu), Wakame, Hirome, Aowakame, Giant Kelp (Macrocystis piriella, Macrocystis integrafolia, Neocity's Leuteciana), Hijiki, Hibamata, Umimata, Usiu Miuchi, Kireba Nouumi Uchiwa, Akaba Miu Uchiwa, Kono Miuchi Uchiwa, Okinauchi Uchiwa, Usuyuki Uchiwa, Ecchi Umi Uchiwa], seaweed [red algae: Hijirimen, magusa (tengusa), hirakusa, onyxa, ovaxa, Taobakusa, Yatabegusa, Yuikiri, Shimatengusa, meristotheca papulosa, Togekirinsai, Amakusa giraffe rhinoceros, Eucheuma, juniper giraffe rhinoceros, Chondrus, Oobatsunomata, Irish moss (Yahazutsunomata), Ezotsunomata, Togetsunomata, Hirakotoji, Kotojitsunomata, Ibotsunomata, Marubatsunomata, Hirakotoji, Suginori, Shikin'nori, Kainori Seaweed extract obtained from, for example, Yaleus banoli, Cagios vanoli, Susius Banoli, Heius Banoli, Akamoginori, Susabinori], or the extract obtained by culturing the above seaweed cells.

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

  (16) Microbial culture metabolite: Yeast metabolite, yeast extract, bacterial metabolite, bacterial extract, mold or actinomycete metabolite, mold or actinomycete extract, natto fungus metabolite, natto extract, rice fermentation Extract, fermented rice bran extract, Euglena extract or its degradation product or water-soluble derivative thereof, trehalose or derivative thereof, lactic acid fermented product of raw milk or skimmed milk powder, fermented product of leguminous plant lactic acid bacteria, coconut plant Lactic acid bacteria fermented products etc.

  (17) Inorganic pigments: anhydrous silica, magnesium silicate, talc, kaolin, bentonite, mica, mica titanium, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, calcium carbonate, magnesium carbonate, yellow iron oxide , Bengara, black iron oxide, gun jow, chromium oxide, chromium hydroxide, carbon black, calamine etc.

  (18) UV absorber / blocker: benzophenone derivative (2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, Dihydroxydimethoxybenzophenone, sodium dihydroxydimethoxybenzophenone-sodium sulfonate, 2,4-dihydroxybenzophenone, tetrahydroxybenzophenone etc., paraaminobenzoic acid derivatives (paraaminobenzoic acid, ethyl paraaminobenzoate, glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate) Octyl paradimethylaminobenzoate, etc., methoxycinnamic acid derivatives (ethyl paramethoxycinnamate, isopropyl paramethoxycinnamate, paramethoxycinnamic acid oc Chill, 2-ethoxyethyl paramethoxycinnamic acid, sodium paramethoxycinnamic acid, potassium paramethoxycinnamic acid, glyceryl mono-2-ethylhexanoate such as diparamethoxycinnamic acid, salicylic acid derivatives (octyl salicylate, phenyl salicylate, homomentyl salicylate, dipropylene glycol salicylate) Ethylene glycol salicylate, myristyl salicylate, methyl salicylate etc., anthranilic acid derivatives (methyl anthranilate etc.), urocanic acid derivatives (eg urocanic acid, ethyl urocanic acid 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 B 6 derivative, umbelliferone, esculin, benzyl cinnamate, cinoxalate, oxybenzone, oxybenzone, dioxybenzone, octazobenzone, slysobenzone, benzoresorcinol, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, neoheliopan, eska Roll, zinc oxide, talc, kaolin etc.

  (19) Whitening agents: para-aminobenzoic acid derivatives, salicylic acid derivatives, anthranilic acid derivatives, 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 derivatives, nicotinic acid derivatives, vitamin C or derivatives thereof (vitamin C phosphate ester 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, rucinol, hydroquinone etc.

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

  (21) Antioxidants: hydroxytyrosol, parahydroxyanisole, propyl gallate, sesamol, sesamoline, gossypol, propolis and the like.

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

  (23) Fragrance: musk, civette, kastriol, angris essential oil, angelica essential oil, ylang ylang essential oil, iris essential oil, fennel essential oil, orange essential oil, cananga essential oil, caraway essential oil, cardamom essential oil, guaiac wood essential oil, cumin essential oil, black essential oil , Cinnamon essential oil, cinnamone essential oil, geranium essential oil, copaiba balsam essential oil, coriander essential oil, sicilian essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, ginger grass essential oil, cedar essential oil, spearmint essential oil, peppermint essential oil, large apricot essential oil, tuberose Essential oil, double-sided essential oil, orange flower essential oil, winter green essential oil, true essential oil, butternut essential oil, rose essential oil, rose essential oil, palma rose essential oil, persimmon essential oil, hiba essential oil, birch essential oil, petigren essential oil, bay essential oil, vetiba essential oil, bergamot essential oil, Peruvian balsam Essential oil, boad rose essential oil, luscious essential oil, mandarin essential oil, eucalyptus essential oil, lime essential oil, lime essential oil, lavender essential oil, linaroe essential oil, lemongrass essential oil, lemon essential oil, rosemary essential oil, Japanese peppermint essential oil etc.

  (24) Dyes and colorants: red cabbage pigment, red rice pigment, red bean pigment, anatase pigment, red pigment, turmeric pigment, enj pigment, krill pigment, green pigment, caramel, gold, silver, gardenia pigment, corn pigment, onion Dyes, tamarind dyes, spirulina dyes, buckwheat whole grass dyes, cherry dyes, nori dyes, hibiscus dyes, grape juice dyes, marigold dyes, purple imo dyes, purple yam dyes, lac dyes, rutin etc.

  Also, according to the external preparation for skin using a rouge ketene extract, a salt of rotogenic acid or a salt of rotogenic acid (sodium rotogenate, calcium rotogenate, magnesium rotogenate, etc.) together with the above-mentioned components, and a skin external preparation containing other components Expression of tyrosinase gene in pigment cells by treatment of compositions containing whitening skin and skin cells and extracts containing rougegenate or salts of rothgenic acid or rotogeneric acid (sodium rotgegenate, calcium rosgegenate, calcium rotgegenate, etc.) How to suppress, thereby suppressing melanin. As the use of the rothgenic acid or its salt according to the present invention, it is also possible to provide as a skin care method for skin lightening and beauty, and a method for treating skin cells.

  Although the preparation examples in the hage kitene extract used by this invention are explained in full detail below, the hage kitene extract of this invention is not limited to the following preparation examples.

Production Example 1 Hage Kitten Extract 3 kg of a 30% aqueous solution of ethanol was added to 100 g of dried Hage Kitten root, soaked for one week, and filtered to obtain 2.4 kg of Hage Kitten extract.
Preparation Example 2 Hage Kitten Extract 3 kg of a 50% aqueous methanol solution was added to 100 g of dried Hage Kitten root, soaked for one week, and filtered to obtain 2.4 kg of Hage Kitten extract.
Production Example 3 Hage Kitten Extract 3 kg of a 70% aqueous solution of ethanol was added to 100 g of dried Hage Kitten root, soaked for one week, and filtered to obtain 2.4 kg of Hage Kitten extract.

(Test 1) Tyrosinase expression suppression (Hage kitene extract)
After culturing the B16 melanoma cells (RIKEN BRC) in a 60 mm dish in D-MEM (Wako) for 24 hours, the samples (the hagekitene extract obtained in Production Examples 1 to 3 are brought to a final concentration of 1%) And control (comparative control) add DMSO to a final concentration of 1% and culture for 1 hour, then add α-MSH (SIGMA-ALDRICH) to a final concentration of 50 ng / mL did. The cells were extracted using RNeasy Mini Kit (QIAGEN) 24 hours after addition of α-MSH, and cDNA was synthesized using PrimeScript RT reagent Kit (Takara Bio Inc.) using the obtained RNA as a template. Using this cDNA, the expression level of Tyrosinase gene was measured by quantitative PCR.
For quantitative PCR, SYBR Premix Ex Taq (Takara Bio Inc.) and Thermal Cycler Dice Real Time System (Takara Bio Inc.) were used. As an internal standard, the expression amount of RPS18 gene which is a housekeeping gene was quantified, the relative expression amount with respect to RPS18 was computed, and it was set as Tyrosinase gene expression amount. As a primer for PCR, Tyrosinase from Takara Bio Inc., RPS18 was used.

(Test results)
It was found that the hage ketene extraction obtained by Preparation Example 3 showed the highest Tyrosinase expression inhibitory effect.

(Test 2) Search for Active Ingredients in Hage Kitten Extract The components specifically contained in the Hage Kitten extract of Preparation Example 3 were searched using HPLC, LC-MS, NMR, etc. using known analysis methods, It has been found that rothgenic acid and ursolic acid are abundantly contained in the hagekitene extract of Preparation Example 3.

  The production examples of rotugenic acid used in the present invention will be described in detail below, but the rotogenic acid of the present invention is not limited to the following production examples, and uses chemical synthesis and enzyme reaction in addition to extraction and purification from animals and plants and cells. Also included are those obtained for the compounds obtained by any means of production.

Production Example 4 Production of Rotogenic Acid According to the previous report (chem. Pharm. Bull. 43 (9) 1462-1465 (1995)), 4 kg of roots of Hage Kitten are extracted three times with 10 L of methanol, and then 1.3 kg. After concentration to dryness, the mixture was partitioned with ethyl acetate-water, and the ethyl acetate layer was concentrated to obtain 75 g of a solid. Furthermore, 75 g of 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 solid content. Thereafter, column purification was performed with a mixture of chloroform and methanol to obtain 110 mg of rotsevenic acid.

(Test 3) LCMS Analysis of Rotsogenic Acid 0.89 mg of rotsogenic 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 (manufactured by Waters)
Mass spectrometer: Xevo G2-S-QTof (manufactured by Waters)
Photodiode array: (210 to 500 nm)
Column: ACQUITY UPLC BEH C18 (50 x 2.1 mm ID, 2.1 μm)
Flow rate: 0.8 mL / min
Column temperature: 55 ° C
Solvent: A solution: 0.1% formic acid aqueous solution, B solution: 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 liquid /% B liquid = 0/100 → 7 min;% A liquid /% B liquid = 0/100

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

(Test 4) NMR Analysis of Rotogenic Acid 13.0 mg of rotegenic acid obtained in Production Example 4 was dissolved in C ₅ D ₅ N (600 μL), and ¹³ C-NMR measurement was performed. Furthermore, the above-mentioned 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 values of the chemical shifts shown in Table 1 and are * consistent with the values described in the previous report (Phytochemistry 28 (5) 1479-1482 (1989)). Identified.
¹³ C NMR physical properties of rotsevenic acid

(Test 5) Preparation of Salt of Rotsogenic Acid The rotsogenic acid obtained according to the above-mentioned Preparation Example was adjusted to the sodium salt and calcium salt of rotsgenic acid by a conventional method.

(Test 6) Tyrosinase expression suppression (rotsugenic acid, ursolic acid)
After culturing B16 melanoma cells (RIKEN BRC) in a 60 mm dish in D-MEM (Wako) for 24 hours, the final concentration of each of the samples (rotsugenic acid obtained in Production Example 4 and ursolic acid (INDOFINE Chemical) at a final concentration of 0.8) A control (comparative control) is DMSO added to a final concentration of 1% so as to be μM, and culture is performed for 1 hour, and then a final concentration of 50 ng / mL of α-MSH (SIGMA-ALDRICH) It added so that it might become. The cells were extracted using RNeasy Mini Kit (QIAGEN) 24 hours after addition of α-MSH, and cDNA was synthesized using PrimeScript RT reagent Kit (Takara Bio Inc.) using the obtained RNA as a template. Using this cDNA, the expression level of Tyrosinase gene was measured by quantitative PCR.
For quantitative PCR, SYBR Premix Ex Taq (Takara Bio Inc.) and Thermal Cycler Dice Real Time System (Takara Bio Inc.) were used. As an internal standard, the expression amount of RPS18 gene which is a housekeeping gene was quantified, the relative expression amount with respect to RPS18 was computed, and it was set as Tyrosinase gene expression amount. As a primer for PCR, Tyrosinase from Takara Bio Inc., RPS18 was used. Furthermore, in order to confirm the concentration dependency of rotsugenic acid, the same procedure was carried out at final concentrations of 0.1 μM, 4 μM and 10 μM.

(Test results)
The results are as shown in FIG. Under the condition that the expression of Tyrosinase gene was enhanced by the addition of α-MSH, ursolic acid was not found to suppress the gene expression. On the other hand, rotugenic acid was found to have a large inhibitory effect on tyrosinase gene expression at a concentration of 0.8 μM. Even under the condition of 0.1 μM of rotogenic acid, although the suppression effect was slightly lower than that of the case of the concentration of 0.8 μM. The sodium salt and calcium salt of rotogenic acid obtained in Test 5 were also added at a final concentration of 0.8 μM, and when Test 6 was performed, similar effects were obtained.

(Example of prescription)
Examples of formulations using rothgenic acid or salts thereof are described below, but are not limited to the formulations of the present 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. Bee wax 1.5
6. Skrawan 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. Methyl paraben amount 15. Propyl paraben Dosage 16. Phenoxyethanol 0.20
17. Make the total amount of purified water 100

(Prescription example 2) W / O lotion weight%
1. Rotogenic acid or its salt 0.001
2. L-arginine 0.20
3.1 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. Penta 12-hydroxystearic acid decaglyceryl 2.0
9. Methyl paraben appropriate amount 10. Make the total amount of purified water 100

(Prescription example 3) Weight% of lotion
1. Rotogenic acid or its salt 0.001
2. Citric acid 0.02
3. Citric acid Na 0.18
4. Pentylene glycol 3.0
5. Diethoxyethyl succinate 15.0
6. Make the total amount of purified water 100

(Formulation example 4) Beauty solution 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. Deka Macadamia Nut Fatty Acid Polyglyceryl-10 0.20
7. Sodium Hyaluronate 0.50
8. Polyglyceryl monooleate 1.50
9.1 1,3-Butylene glycol 3.00
10. Maltose (75% aqueous solution) 1.00
11. Glycerin 4.00
12. Carboxy vinyl polymer 11.25
13. Edetate tetrasodium 0.10
14. Xanthan gum (2% aqueous solution) 3.75
15. Methyl paraben amount 16. Phenoxyethanol 0.20
17. Make the total amount of purified water 100

(Formulation example 5) Emulsion% by weight
1. Rotogenic acid or its salt 0.001
2. Hydroxypropyl starch phosphate 2.0
3. Setostearyl rucoal 2.0
4. Sorbitan stearate 2.0
5. PPG-15 Stearyl 4.0
6. Trioctanoin 5.0
7. Tricapryl glycerin 5.0
8. Dimethicone 1.0
9. Glycerin 4.0
10. Phenoxyethanol 0.20
11. Methyl paraben amount 12. Make the total amount of purified water 100

(Prescription example 6) Whitening cream weight%
1. Rotogenic acid or its salt 0.001
2. Condensed ricinoleate hexaglyceryl 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 ethylhexanoate 7.0
8. Methyl phenyl polysiloxane 5.0
9. Glycerin 8.0
10. Methyl paraben appropriate amount 11. Vegetable Ceramide (Yuzu) 0.5
12. Make the total amount of purified water 100

(Prescription example 7) Massage cream weight%
1. Rotogenic acid or its salt 0.001
2. Sodium hydroxide 1.0
3. Carbomer 20.0
4. Mannan 8.0
5. Castor oil 3.0
6. Diphenyl methicone 0.05
7. Cetearyl alcohol 1.5
8. Phenyl trimethicone 4.5
9. Ceramide 0.3
10. BG 5.0
11. Glycosyl Trehalose 8.0
12. Glycerin 3.0
13. Methyl paraben 0.20
14. Make the total amount of purified water 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. Methyl paraben 0.20
7. Ethanol 10.0
8. Make the total amount of purified water 100

(Formulation example 9) After shave 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. Methyl paraben amount 12. Make the total amount of purified water 100

(Formulation example 10) Liquid foundation weight%
1. Rotogenic acid or its salt 0.001
2. Polyglyceryl pentaisostearate-1.5
3. Triethylhexyl citrate 6.0
4. Monosodium glutamate 0.50
5. Skrawan 3.0
6. Glycerin 5.0
7. Methyl polysiloxane 0.50
8. Decamethylcyclopentasiloxane 10.0
9. Pigment 15.0
10. Methyl paraben appropriate amount 11. Make the total amount of purified water 100

(Formulation example 11) Lipstick weight%
1. Rotogenic acid or its salt 0.001
2. Hydrogenated olive stearyl esters 3.0
3. Isotrinodecyl isononanoate 5.0
4. Olefin oligomer 14.0
5. Polyglyceryl triisostearate-2 14.7
6. Hydrogenated polyisobutene 18.0
7. Tocopherol 0.10
8. Polyethylene 5.0
9. Candelilla Law 6.5
10. Hydrogenated rosin acid pentaerythritol 12.0
11. Hydroxyapatite 1.0
12. Microcrystalline wax 3.0
13. Silylated silica 0.50
14. Red 202, polyglyceryl triisostearate-0.75
15. Titanium oxide, Al hydroxide
Polyglyceryl triisostearate-0.90
16. Iron oxide, polyglyceryl triisostearate-2 1.20
17. Blue 1, polyglyceryl triisostearate-0.15
18. Titanium oxide, mica 5.0
19. Propyl paraben 0.10
20. Isododecane 9.0

(Formulation example 12) Eye shadow 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 sesquioelate 2.0
6. Talc 3.0
7. Liquid paraffin 8.0
8. Pigment 5.0
9. Flavoring amount 10. Antiseptic suitable amount

(Formulation example 13) Weight% of cleansing oil
1. Rotogenic acid or its salt 0.001
2. Diethoxyethyl succinate 3.0
3. Pentylene glycol 3.0
4. Sodium citrate appropriate amount 5. Polyglyceryl triisostearate-2 3.0
6. PEG-10 Glyceryl Diisostearate 5.0
7. Triisostearic acid PEG-30 15.0
8. Purified water 1.5
9. The total amount of neopentyl glycol diisononanoate is 100

(Formulation example 14) Shampoo weight%
1. Rotogenic acid or its salt 0.001
2. Guar hydroxypropyl trimonium chloride 0.10
3. Hydrolyzed collagen 0.20
4. PCA 2.0
5. Cocoyl glutamate K 2.0
6. Cocamide DEA 3.0
7. Lauramidopropyl betaine, water, sodium chloride 4.0
8. Lauryl sulfate TEA 22.0
9. Flavoring 0.10
10. Methyl paraben appropriate amount 11. Make the total amount of purified water 100

(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. Diastearate 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. Flavoring agent 0.1
13. Methyl paraben amount 14. Make the total amount of purified water 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. Ethylhexyl hydroxystearate 5.0
5. Polyglyceryl isostearate-1 .50
6. Glyceryl stearate 2.0
7. (Polyglyceryl isostearate-2
/ Dimeric linoleic acid) copolymer 4.50
8. Hydroxide K 0.08
9. Dimethicone 2.0
10. Carbomer 0.30
11. Make the total amount of purified water 100

(Prescription example 17) Acidic hair dye weight%
1. Rotogenic acid or its salt 0.001
2. Dye 0.50
3. Glycolic acid 5.0
4. Bisethoxy diglycol succinate 5.0
5. Hydroxyethylcellulose 2.0
6. Ethanol 15.0
7. Make the total amount of purified water 100

(Formulation example 18) Hair rinse weight%
1. Rotogenic acid or its salt 0.001
2. Copper Chlorophyll Na 0.10
3. Hydrolyzed collagen 0.50
4. Stealtrimonium chloride 8.0
5. Brown algae extract 0.20
6. Dextrin palmitate 0.20
7. Dipenta Eristyl 1.0
8. Tanakla Clay 1.0
9. Mineral oil 3.0
10. Setanol 5.0
11. Ores-8 2.0
12. Citric acid 0.10
13. Flavoring 0.10
14. Methyl paraben amount 15. Propyl paraben Dosage 16. Dimethicone 0.50
17. Butylene glycol 6.0
18. Make the total amount of purified water 100

(Prescription example 19) Hair treatment weight%
1. Rotogenic acid or its salt 0.001
2. Shirakaraba extract 0.50
3. Sage extract 0.50
4. Stealtrimonium chloride 1.50
5. Distealdimonium chloride 1.50
6. Hydrolyzed collagen 2.0
7. Hydroxyethyl cellulose 0.10
8. Steareth-15 1.0
9. Behenyl alcohol 2.0
10. Setanol 3.0
11. Sri Chill 1.0
12. Methyl paraben amount 13. Propyl paraben Dosage 14. Dipropylene glycol 5.0
15. Make the total amount of purified water 100

(Formulation 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. Make the total amount of purified water 100

(Formulation example 21) Shaving cream% by weight
1. Rotogenic acid or its salt 0.001
2. TEA 3.0
3. Trioctaine 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. Flavoring 0.10
10. Methyl paraben appropriate amount 11. Butylene glycol 8.0
12. Make the total amount of purified water 100

(Formulation example 22) sunscreen cream 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. Skrawan 8.0
8. Dimethicone 0.5
9. (Dimethicone / vinyl dimethicone) crosspolymer 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. Methyl paraben 0.2
18. Propyl paraben 0.05
19. Glycerin 2.0
20. Butylene glycol 5.0
21. Make the total amount of purified water 100

(Formulation example 23) Body shampoo weight%
1. Rotogenic acid or its salt 0.001
2. Skrawan 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. Lauramide propyl betaine 25.0
9. EDTA-2Na 0.1
10. Fragrance 0.2
11. Methyl paraben 0.3
12. Propylene glycol 11.0
13. Make the total amount of purified water 100

(Formulation example 24) Hand soap weight%
1. Rotogenic acid or its salt 0.001
2. Kari Stone Ken 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. Methyl paraben 0.1
9. Glycerin 8.0
10. Make the total amount of purified water 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. Lauramide propyl betaine 6.0
7. Capryloyl glutamate Na 10.0
8. Cocamide DEA 1.0
9. Flavoring agent 0.1
10. Methyl paraben appropriate amount 11. Make the total amount of purified water 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. Lauramide propyl betaine 15.0
10. Stearic acid 7.0
11. Palmitic acid 9.0
12. Myristic acid 14.0
13. Methyl paraben amount 14. Make the total amount of purified water 100

(Prescription example 27) Bath salt 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. Dry sodium sulfate to 100 in total

(Formulation 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. Skrawan 5.0
6. Dimethicone 0.20
7. Phenyl trimethicone 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. Methyl paraben amount 14. Propyl paraben Dosage 15. Butylene glycol 8.0
16. Make the total amount of purified water 100

(Formulation 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 ester 0.30
5. Precipitable silica 15.0
6. Sodium chloride 5.0
7. Sodium hydroxide 0.25
8. Sodium lauryl sulfate 1.50
9. Carboxymethylcellulose sodium 0.80
10. Carrageenan 0.60
11. Thickening silica 4.0
12. Citric acid 0.10
13. Saccharin sodium 0.18
14. Flavoring 1.30
15.70% sorbit solution 45.0
16. Propylene glycol 3.0
17. Make the total amount of purified water 100

(Formulation example 30) Cosmetic liquid for eyelashes weight%
1. Rotogenic acid or its salt 0.001
2. Glucosyl hesperidin 0.10
3. Hydroxyethyl cellulose 0.50
4. Carboxy vinyl polymer 1.0
5. Edetate trisodium 0.02
6. Triethanolamine 0.20
7. Methyl paraben 0.20
8. Ethanol 5.0
9.1 1,3-Butylene glycol 5.0
10. Make the total amount of purified water 100

(Formulation example 31) Eyebrows, hair growth gel for eyelashes weight%
1. Rotogenic acid or its salt 0.001
2. EO modified silicone 1.0
3. Amphoteric polymer 1.0
4. Carboxy vinyl polymer 0.5
5. Monoisostearate decaglycerin 4.0
6. POE (30) Isocetyl ether 0.5
7. Methyl paraben 0.1
8. Sodium bisulfite 0.05
9. Edetate disodium 0.05
10. Fragrance 0.5
11. 12. Triethanolamine. Ethanol 10.0
13. Make the total amount of purified water 100

(Formulation 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. Perfume 0.20
6. LPG dosage

(Test 7) Feeling test on use Rotogenic acid, Na lauryl sulfate, and purified water were dispersed at a weight ratio of 30: 3: 67, and wet ground by a high-pressure homogenizer. Grinding conditions are: treatment pressure: 200 MPa, number of times of treatment: 80 times, and the obtained suspension is made into whitening cream of 3 kinds of prescription a to c shown in Table 2 below based on prescription example 6 The panelists evaluated the feeling of use. The evaluation items of the feeling of use are the spread at the time of application and the smoothness after application.

(Test results)
As shown in Table 3 below, the average score is 3 or more at 1% and 5% mass concentration of rotogenic acid, but the average score is 2 or less at 7%, and the mass concentration of rotegenic acid in the external preparation is 5 If it is% or less, it is predicted that an external preparation with a good feeling of use can be obtained.
(Scoring criteria)
5: very good feeling of use 4: good feeling of use 3: normal feeling of use 2: not good feeling of good use 1: not good feeling of use

(Test 8) Use effect test Based on Formulation Example 6 of the present invention, four types of whitening creams of Formulations A to D shown in Table 4 below were produced. The prepared skin-whitening cream was applied twice daily to the face of 20 male and 20 male and 20 female men and women, and used for 1 month. The subjects were divided into 5 subjects each and their spots and pigmentation were evaluated in comparison with those before use.

(Test results)
As a result, as shown in Table 5 below, it was recognized that the formulation containing rotsogenic acid was higher than the control product, and in particular, the formulation B containing 0.1% was higher than the other formulations.
Effective: The stains and pigmentation were improved more than before use.
Slightly effective: The stains and pigmentation are slightly improved compared to before use.
Disabled: No change before use.

Claims (6)

  A skin external preparation containing rotsgenic acid or a salt thereof.   A skin whitening preparation for external use, which comprises rotogenic acid or a salt thereof.   A whitening agent containing rotsgenic acid or a salt thereof.   An external preparation for skin containing a hagekitene extract essentially comprising rothgenic acid or a salt thereof.   An external preparation for whitening skin comprising a hagekitene extract essentially comprising rothgenic acid or a salt thereof.   A whitening agent comprising a hagekitene extract which essentially comprises rothgenic acid or a salt thereof.