JP5089888B2 - Fugu-derived collagen, derivatives thereof, production method thereof, and cosmetics containing the collagen and derivatives thereof - Google Patents

Description

  The present invention relates to collagen and / or collagen derivatives in which puffer venom is detoxified, a method for producing the same, and a cosmetic comprising the collagen and / or collagen derivative.

  Collagen is a major protein that forms the skin of animals such as cow skin, pig skin, and fish skin. Collagen is used in a large amount as a raw material for cosmetics because it has moisturizing properties and gives a smooth feel to the skin. Collagen is also used for pharmaceuticals and medical devices because it has excellent biocompatibility. Furthermore, collagen has attracted attention as a functional food material and has come to be used in various fields such as drinks and jelly-like foods. Collagen used in this way is mainly derived from cow skin and pork skin. In recent years, infectious diseases such as cattle mad cow disease and pig foot-and-mouth disease occur frequently, Sex has become a problem. Under these circumstances, collagen other than mammals has been actively developed for safety and new functions. Among them, fish skin-derived collagen and collagen derivatives are partly used, but have a drawback of low moisture retention. For example, conventional collagen obtained from marine products has low product purity and fishy odor, for example, collagen obtained from fish skin, so mechanical pre-processing steps, mixing steps, and water washing steps are necessary to solve it. Is disclosed (JP-A-5-202097) and organic solvent treatment and high-speed centrifugal separation process (JP-A 2000-256398), but the collagen obtained by this method has low moisture retention, The practicality was low.

On the other hand, the pufferfish-derived collagen has high moisture retention, but the pufferfish venom is also present in the fish skin, so it has a drawback that it cannot be used safely in cosmetics.
With regard to the method for producing pufferfish collagen, boiled puffer skin is boiled in an alcohol-containing aqueous solution to extract collagen, and the resulting collagen is stirred together with vegetable gelatin in water to administer a corrosion inhibitor, followed by boiling. A method for producing pufferfish collagen characterized by maintaining the state and boiled is disclosed. However, this method cannot detoxify the puffer venom, and the collagen molecule is denatured by heating, and should be called gelatin instead of collagen. (Japanese Patent Laid-Open No. 8-283665)

The pufferfish has been eaten for a long time, but there is a pufferfish poison called tetrodotoxin in the ovary, liver and some puffer skins of pufferfish. It is said that it must be. Among the pufferfishes, many of them belong to the genus Trafugu and Sabafugu, which include tiger pufferfish, crow puffer, mafugu, pufferfish, etc., and the Sabafugu genus includes white-spotted pufferfish, black-spotted pufferfish, and blackfish pufferfish. Since the fish skin of puffer fish is also eaten, there are many fish skins that do not contain puffer poison, but some puffers such as pufferfish contain puffer poison in the fish skin. In addition, the pufferfish belonging to the genus Torafugu are close to each other in genetic distance, and natural hybrid pufferfish are recognized, and there are many pufferfish × pufferfish × pufferfish × pufferfish. There are many pufferfish poisons in the fish skin of these hybrid pufferfish. If the pufferfish is before treatment, the puffer fisherman or puffer cook will determine the presence or absence of puffer poison. However, if only puffer fish skin is found, it may be misjudged. However, since there is a high risk of contamination of fish skin of hybrid pufferfish containing pufferfish poison, there has been a strong demand for the development of detoxified pufferfish-derived collagen that can be used safely.
Japanese Patent Laid-Open No. 5-202097 JP 2000-256398 A JP-A-8-283665

  An object of the present invention is to provide a puffer fish skin-derived collagen and / or a derivative thereof, in which a puffer venom is detoxified, and a method for producing the same, as well as a cosmetic composition containing the same.

  As a result of intensive studies to achieve the above object, the present inventors have found that detoxified collagen can be obtained by alkali treatment and hydrous ethanol treatment, and have completed the present invention.

That is, the present invention
(1) A collagen derived from puffer fish skin and / or a derivative thereof, wherein the pufferfish poison is detoxified.
(2) The collagen and / or derivative thereof according to (1), which is obtained by subjecting puffer fish skin to alkali treatment and hydrous ethanol treatment.
(3) The collagen and / or derivative thereof according to (2), wherein the alkali treatment is performed at 10 ° C. or lower using a hydroxide.
(4) The collagen and / or derivative thereof according to (1) to (3), wherein the pufferfish is one or more selected from pufferfish belonging to the pufferfish family, Tufffish, Sabafugu.
(5) The collagen and / or derivative thereof according to (1) to (4), wherein the derivative is an atheromatized and / or acylated derivative.
(6) The collagen and / or derivative thereof according to (1) to (5), wherein the acylated derivative is a succinyl derivative.
(7) A method for producing collagen derived from puffer fish skin and / or a derivative thereof, characterized in that pufferfish poison is detoxified.

(8) The method for producing collagen and / or a derivative thereof according to (7), which is obtained by subjecting puffer fish skin to alkali treatment and hydrous ethanol treatment.
(9) The method for producing collagen and / or a derivative thereof according to (8), wherein the alkali treatment is performed at 10 ° C. or lower using a hydroxide.
(10) The production of collagen and / or a derivative thereof according to (7) to (9), wherein the pufferfish is one or more selected from pufferfish belonging to the pufferfish genus Trafugu and Puffyfish Method.
(11) The method for producing collagen and / or a derivative thereof according to (7) to (10), wherein the derivative is an atelolated and / or acylated derivative.
(12) The method for producing collagen and / or a derivative thereof according to (7) to (11), wherein the acylated derivative is a succinylated derivative.
(13) A cosmetic comprising a collagen derived from a puffer fish skin and / or a derivative thereof, wherein the puffer poison is detoxified.
(14) The cosmetic according to (13), characterized in that collagen and / or a derivative thereof obtained by subjecting puffer fish skin to alkali treatment and hydrous ethanol treatment are blended.

(15) The cosmetic material according to (14), wherein the alkali treatment is performed at 10 ° C. or lower using a hydroxide.
(16) The cosmetic composition according to (13) to (15), wherein the pufferfish is one or more selected from pufferfish belonging to the pufferfish genus Trafugu and the pufferfish.
(17) The cosmetic according to (13) to (16), wherein the derivative is an atelolated and / or acylated derivative.
(18) The cosmetic according to (13) to (17), wherein the acylated derivative is a succinylated derivative.

  According to the present invention, it is possible to obtain a collagen derived from a puffer fish fish skin in which a puffer venom is detoxified, which can be effectively used in cosmetics and the like, and an excellent moisturizing property is obtained.

  The collagen of the present invention can be used in an aqueous solution of an inorganic acid such as dilute hydrochloric acid or dilute phosphoric acid, an organic acid aqueous solution such as dilute acetic acid, dilute lactic acid, dilute glycolic acid or dilute citric acid, or a solution thereof. It can be used even in a dried state. On the other hand, examples of the collagen derivative of the present invention include atelotates, acylated derivatives, alkylated derivatives and the like, and any derivative may be used as long as it is neutral and dissolves in water. Among acylated puffer fish skin-derived atelocollagen, acylated atelocollagen such as succinylated atelocollagen, phthalated atelocollagen, maleylated atelocollagen and their salts are neutral and soluble in water, so they must be dissolved in pure water. However, if necessary, it can be dissolved in a buffer solution such as a phosphate buffer solution. It can also be used in a dried state.

  Detoxification of puffer fish can be achieved by treating the fish skin with an alkali and further carrying out a hydrous ethanol treatment. Here, detoxification refers to food sanitation inspection guidelines of RIKEN (Ministry of Health, Labor and Welfare, 2005), Chapter 7.

  The raw puffer fish skin can be used in any pufferfish family, but it is preferable to use pufferfish and / or mackerel pufferfish. It is particularly preferable to use tiger puffer, crow puffer, and puffer puffer as the puffer puffer, and it is particularly preferable to use the puffer puffer. You can select any puffer fish and use the fish skin, but for production, the fish skin that is discharged in the cooking / processing process is quantitatively preferable. It consists of two or more puffer fish skins. Can also be used in the present invention.

  A method for separating and removing the pigment layer from the puffer fish skin may be processed by a general physical method and a chemical method. That is, a method of physically removing a layer having pigment cells with a sharp object such as a knife, a method of using a device such as a homogenizer or a mixer, a method of using water pressure, a method of treating with a dilute acid such as a dilute organic acid, Examples thereof include a method using an enzyme such as protease, and these may be used in combination. In addition, some puffer fish skins have thorns, and these are not edible as they are, so put a knife blade between the dermis and the epidermis, and peel off the epidermis along with the thorns. It is also possible to use the fish skin that has been performed. Subsequently, the alkali treatment is carried out. The alkali treatment may be carried out by immersing the skin in an aqueous solution of sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonia water, ethanolamine or the like. The alkali used is preferably a hydroxide, more preferably sodium hydroxide or potassium hydroxide. The concentration of the aqueous hydroxide solution is not particularly limited as long as the puffer venom is reduced and the yield can be secured, but it is preferable to use an aqueous hydroxide solution having a concentration of 0.05 mol / L to 2.0 mol / L, more preferably 0.2. It is a hydroxide aqueous solution having a concentration of mol / L to 1.0 mol / L. The temperature for carrying out the alkali treatment is preferably 10 ° C. or lower. Here, when processing temperature is high, collagen will melt | dissolve in an alkali and a yield will fall remarkably. Next, the hydroalcoholic treatment is performed. The hydroalcoholic treatment may be performed by immersing the puffer fish skin in a solution such as hydrous methanol, hydrous ethanol, hydrous isopropyl alcohol or the like. The alcohol to be used is preferably ethanol or denatured ethanol. The alcohol concentration of the hydrous alcohol is preferably 50 to 95% by weight, and it is preferably carried out at 10 ° C. or less in order to prevent collagen denaturation. The obtained pufferfish fish skin from which pufferfish poison has been detoxified can be further subjected to normal purification treatment to remove lipids and impure proteins. That is, it is possible to carry out a washing step using a salt solution such as sodium chloride, potassium chloride, sodium acetate, sodium citrate, sodium hydrogen phosphate or the like.

  In addition, in order to degrease the obtained puffer fish skin, organic solvents such as alcohols such as methanol, ethanol and isopropyl alcohol, ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether and tetrahydrofuran, ethyl acetate and the like Esters, organic halogen compounds such as methylene chloride, chloroform and carbon tetrachloride, hydrocarbons such as hexane and heptane, nitrogen-containing organic solvents such as acetonitrile and pyridine, glycerin, diglycerin, 1,3-butylene glycol, ethylene Glycols such as glycol and polyethylene glycol, aromatic organic compounds such as benzene, toluene, and xylene, and other organic solvents such as N, N-dimethylformamide, dimethylsulfoxide, and N, N-dimethylacetamide Or, after the organic solvent treatment with a mixed solution of these organic solvents with water, it can be implemented as needed a step of centrifugation.

  The obtained puffer fish skin is subjected to acid extraction using dilute organic acids such as acetic acid, citric acid and lactic acid, and dilute inorganic acids such as hydrochloric acid and phosphoric acid, whereby collagen is obtained. That is, dilute acetic acid solution with a concentration of 0.01-2 mol / L, dilute lactic acid solution with a concentration of 0.001-2 mol / L, dilute citric acid solution with a concentration of 0.001-2 mol / L, dilute hydrochloric acid solution with a concentration of 0.001-0.2 mol / L, Add pufferfish fish skin with pufferfish poison to acid solution such as dilute phosphoric acid solution with a concentration of 0.001-0.5 mol / L, and keep it at 10 ° C or lower, preferably 2-8 ° C, 1-240 hours, preferably 24- Collagen is extracted by stirring for 96 hours.

  When the insoluble matter remains in the extracted collagen solution, it is desirable to remove the insoluble matter by filtration or centrifugation. Since the obtained collagen is dissolved in the acid solution, it can be used as it is, but is preferably further purified. That is, collagen is precipitated by salting out by adding a salt to the collagen solution, organic solvent precipitation by adding an organic solvent, isoelectric point precipitation by adding a base, and separating the resulting precipitate. Is purified. The salt used in the salting-out method can be any salt that precipitates collagen, but sodium chloride, sodium sulfate, sodium citrate, phosphoric acid is considered from the viewpoint of economy and safety. Sodium or the like is desirable. The organic solvent used in the organic solvent precipitation method may be any organic solvent that can be mixed with water, but alcohols and ketones mixed with water are preferred. Furthermore, the base used in the isoelectric point precipitation method can be any base as long as it is water-soluble, but from the viewpoint of economy and safety, hydroxide such as sodium hydroxide, monoethanolamine, etc. Organic amine and ammonia are desirable. The obtained precipitate can be dissolved again in the acid solution described above or the acid buffer solution described above to obtain a product. However, in the salting-out method, the salt is used. In the point precipitation method, since salt remains in the precipitate, these impurities can be removed by dialysis, ultrafiltration, washing operation, or the like. It is also possible to obtain a collagen solution from which impurities have been removed as a dried product by a drying method such as a freeze drying method or a spray drying method.

  On the other hand, the collagen derivative of the present invention is obtained by the following method. In other words, detoxified puffer fish skin is extracted with dilute organic acids such as acetic acid, citric acid, and lactic acid, and dilute inorganic acids such as hydrochloric acid and phosphoric acid, and at the same time treated with acidic protease such as pepsin to obtain atelocollagen. It is done. That is, dilute acetic acid solution with a concentration of 0.01-2 mol / L, dilute lactic acid solution with a concentration of 0.001-2 mol / L, dilute citric acid solution with a concentration of 0.001-2 mol / L, dilute hydrochloric acid solution with a concentration of 0.001-0.2 mol / L, Add the pufferfish fish skin from which puffer toxin has been removed to an acid solution such as dilute phosphoric acid solution with a concentration of 0.001-0.5 mol / L, and then add an acidic protease, at 10 ° C or lower, preferably 2-8 ° C, 1-240 Atelocollagen is extracted by stirring for a period of time, preferably 24-96 hours.

  Any protease can be used as the protease for atelolysis as long as it catalyzes the hydrolysis of peptide bonds, preferably degradation by acidic protease, more preferably degradation by pepsin. The amount added may be 0.01% to 30% with respect to collagen, but is preferably 0.1% to 10%, and particularly preferably 1% to 5%.

The collagen derivative can be easily obtained by chemically modifying atelocollagen obtained from puffer fish skin by a conventional method by the above-described method. For example, denatured collagen and gelatin can be obtained by adding atelocollagen to an aqueous solvent and heating to 40 ° C to 100 ° C. On the other hand, the acylation reaction of atelocollagen is adjusted to pH 9-12 by adding alkali such as sodium hydroxide and sodium carbonate to the atelocollagen solution, and then acid anhydride such as succinic anhydride, phthalic anhydride, maleic anhydride, acetic anhydride, etc. In order to prevent the pH of the reaction system from lowering, the reaction is carried out while adding alkali to adjust the pH to 9-12. The reaction temperature is preferably 10 ° C. or lower, preferably 2-8 ° C. to prevent atherocollagen denaturation. The acylating agent may be any as long as it can carboxylate the ε-amino group of collagen, preferably an acid anhydride such as succinic anhydride, phthalic anhydride, maleic anhydride, and particularly preferably succinic anhydride. . The acylation rate (modification rate with respect to εNH ₂ ) of acylated atelocollagen can be adjusted by the addition amount. The acylation rate of preferable acylated atelocollagen is 60% to 100%, and the resulting solubility and compatibility are significantly improved, so that it can be suitably blended into cosmetics. The amount of the acylating agent added at this time can be 0.01 mmol / g to 50 mmol / g with respect to collagen, preferably 0.1 mmol / g to 20 mmol / g, particularly preferably 0.5 mmol / g to 5 mmol / g.

  After completion of the reaction, the obtained acylated atelocollagen can be purified by a conventional method. That is, the acylated atelocollagen is precipitated by adding a salt to the acylated atelocollagen solution for precipitation, an organic solvent precipitation method for adding an organic solvent, an isoelectric point precipitation method for adding an acid, and the like. By washing, acylated atelocollagen is obtained. The acylated atelocollagen is washed with an aqueous solution near the isoelectric point of the acylated atelocollagen.For example, in the case of succinylated atelocollagen having an isoelectric point near pH 4.5, acidic water having a pH of 4.0 to 5.0, a water-containing organic solvent, etc. It is possible to use. Acidic water can be prepared using any acid, but it is preferably prepared using dilute hydrochloric acid, dilute acetic acid, dilute citric acid, dilute lactic acid and the like. It can also be used as a buffer for these acids. The organic solvent used for the water-containing organic solvent can be any organic solvent that can be mixed with water, but alcohols and ketones are preferred.

  The puffer fish skin-derived collagen and / or its derivatives in which the puffer poison of the present invention has been detoxified can be used in various fields such as pharmaceuticals, medical devices, cosmetics, and foods. Cosmetics that contain collagen and / or derivatives thereof derived from pufferfish fish skin that has been detoxified with pufferfish poison include basic cosmetics such as skin lotion, milky lotion, beauty essence, and general cream, facial cleansers such as cleansing creams, packs, salmon Shaving cream, tanning cream, sunscreen cream, sunscreen lotion, tanning lotion, cosmetic soap, foundation, funny, powder, lipstick, lip balm, eyeliner, eye cream, eyeshadow, mascara, bath cosmetic, shampoo, rinse, It can be used for various cosmetics such as hair dyes and hair cosmetics. The blending amount is not particularly limited, but is preferably about 0.001 to 100% in the cosmetic composition, more preferably 0.01% to 45%, and still more preferably 0.1 to 25%. In the case of a bath preparation, the prescription may be considered so that it is poured into 200 to 300 L of bath water to obtain a similar concentration.

  The cosmetics of the present invention can be produced by arbitrarily selecting and using in combination the various components and additives that are usually used in cosmetics such as cosmetics as shown below. . For example, avocado oil, almond oil, fennel oil, sesame oil, olive oil, orange oil, orange rafa oil, sesame oil, cocoa butter, chamomile oil, carrot oil, cucumber oil, beef tallow fatty acid, safflower oil, shea fat , Soybean oil, camellia oil, corn oil, rapeseed oil, persic oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, cocoa butter, palm oil, palm kernel oil, owl, coconut oil, beef tallow, Fats and oils such as pork fat or hydrogenated products of these fats and oils (hardened oil etc.).

  Waxes such as beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax. Mineral oils such as liquid paraffin, petrolatum, paraffin, ozokelide, ceresin, microkristane wax, squalene, squalane and pristane. Natural fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, 12-hydroxystearic acid, undecylenic acid, tall oil, lanolin fatty acid. Synthetic fatty acids such as isononanoic acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid and isopentanoic acid.

  Natural alcohols such as ethanol, isopropanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterol. Synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, and 2-octyldodecanol. Ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol, polypropylene glycol, 1,3-butylene glycol , Polyhydric alcohols such as glycerin, pentaerythritol, sorbitol, mannitol.

Isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, diethyl phthalate, phthalate Esters such as dibutyl acid, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate.
Metal soap such as aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, zinc undecylenate.

  Gum arabic, benzoin rubber, danmar gum, guaiac gum, Irish moss, Karaya gum, tragacanth gum, carob gum, quinseed, agar, casein, lactose, fructose, sucrose and its esters, trehalose and its derivatives, dextrin, gelatin, pectin, starch, Carrageenan, succinyl chitosan, 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, sulfated chitin or Chitosan, phosphorylated chitin or chitosan, alginic acid and its salt, hyaluronic acid and its salt, chondroitin sulfate and its salt, heparin, ethylcellulose, methylcellulose, carboxy Polyalkylene such as methyl cellulose, carboxyethyl cellulose, sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate, polyethylene oxide and polypropylene oxide Oxides or their cross-linked polymers, carboxyvinyl polymers, gums such as polyethyleneimine, sugars and water-soluble polymer compounds.

  Anionic surfactant (alkyl carboxylate, alkyl sulfonate, alkyl sulfate ester salt, alkyl phosphate ester salt), cationic surfactant (alkylamine salt, alkyl quaternary ammonium salt), amphoteric surfactant: carboxylic acid Type amphoteric surfactant (amino type, betaine type), sulfate ester type amphoteric surfactant, sulfonic acid type amphoteric surfactant, phosphate ester type amphoteric surfactant, nonionic surfactant (ether type nonionic surfactant) Agent, ether ester type nonionic surfactant, ester type nonionic surfactant, block polymer type nonionic surfactant, nitrogen-containing type nonionic surfactant), other surfactants (natural surfactant, protein Hydrolyzed derivatives, polymer surfactants, surfactants containing titanium and silicon, fluorocarbon surfactants Surfactants such as.

  Retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A), thiamine hydrochloride, thiamine sulfate (vitamin B1), riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin ( Vitamin B12), folic acids, nicotinic acids, pantothenic acids, biotins, choline, inositols, ascorbic acid and its derivatives, ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), dihydrotachysterol, tocopherol and its Derivatives, ubiquinones, phytonadione (vitamin K1), menaquinone (vitamin K2), menadione (vitamin K3), menadiol (vitamin K4), other essential fatty acids (vitamin F), carni Down, ferulic acid, γ- oryzanol, orotic acid, vitamin P compounds (rutin, Elio citrine, hesperidin), vitamins such as vitamin U. Valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, histidine And amino acids such as sulfates, phosphates, nitrates, citrates, and amino acid derivatives such as pyrrolidone carboxylic acids.

  Microbial culture metabolites such as yeast metabolites, yeast extract, rice fermented extract, rice bran fermented extract, Euglena extract and trehalose or its derivatives. Α-hydroxy acids such as glycolic acid, citric acid, malic acid, tartaric acid and lactic acid. 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, red iron oxide, black iron oxide , Inorganic pigments such as Gunjo, chromium oxide, chromium hydroxide, carbon black, calamine.

  p-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, UV absorbers / blockers such as allantoin derivatives, nicotinic acid derivatives, vitamin B6 derivatives, benzophenones, oxybenzone, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, neoheliopan, urocanic acid derivatives, escalol, zinc oxide, talc, kaolin .

  Whitening agents such as arbutin, guaiazulene, shikonin, baicalin, baicalein and berberine. Ascorbic acid and derivatives thereof, hydroquinone and glycosides thereof, kojic acid and derivatives thereof, placenta extract, silk peptide, plant extract (mulberry, honeysuckle, wormwood, mugwort, honeysuckle, yellowfin, dokudami, matsuhod, pearl barley, oleander, hawthorn, Eucalyptus, Achillea millefolium, Altea, Keihi, Mankeishi, Hamameris, Yamagua, Prolonged grass, Kikyo, Toshishi, Seicho, Ishiboshi, Mao, Senkyu, Dokatsu, Psycho, Bowfish, Hamaboufu, Ogon, Peonies, Genus Shouko, Licorice, Pyrus Tyrosinase activity inhibitors such as aloe, shouma, safflower, and assen.

  Melanin pigment reducing / decomposing agents such as hydroquinone monobenzyl ether, phenylmercury hexachlorophene, mercuric oxide, mercuric chloride, hydrogen peroxide, zinc peroxide. Hydroquinone, Lactic acid bacteria extract, Placenta extract, Ganoderma extract, Vitamin A, Vitamin E, Allantoin, Spleen extract, Thymus extract, Yeast extract, Fermented milk extract, Plant extract (Aloe, Ogon, Horsetail, Gentian, Burdock, Shikon, Carrot, Activators / cell activators of turnover, such as hamamelis, hops, yokuinin, nettle, sea bream, cypress, red bellflower, achacha, hypericum, cucumber, ginger, rosemary, parsley, etc. Astringents such as succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc p-phenolsulfonate, potassium aluminum sulfate, resorcin, ferric chloride, and tannic acid (including catechin compounds).

  Active oxygen scavengers such as SOD, catalase, glutathione peroxidase. Ascorbic acid and its salt, stearic acid ester, tocopherol and its ester derivative, nordihydrogua ceretenoic acid, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), hydroxytyrosol, parahydroxyanisole, propyl gallate, sesamol , Antioxidants such as sesamorin and gossypol.

  Lipid peroxide production inhibitors such as β-carotene, plant extracts (sesame cultured cells, amacha, hypericum, hamamelis, clove, melissa, enamel, birch, sage, rosemary, nantenami, kina, ages, ginkgo, etc.). Ictamol, indomethacin, kaolin, salicylic acid, sodium salicylate, methyl salicylate, acetylsalicylic acid, diphenhydramine hydrochloride, d or dl-camphor, hydrocortisone, guaiazulene, camazulene, chlorpheniramine maleate, glycyrrhizic acid and its salt, glycyrrhetinic acid and its salt, Anti-inflammatory agents such as licorice extract ingredients, sicon extract, and ages extract.

  Acrinol, sulfur, benzalkonium chloride, benzethonium chloride, methylrosaniline chloride, cresol, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin or its hydrolyzate, alkyldiaminoethylglycine chloride solution, isopropylmethylphenol, triclosan, kudin Disinfectant / disinfectant.

  Moisturizing such as glycerin, propylene glycol, 1,3-butylene glycol, hyaluronic acid and its salt, polyethylene glycol, chondroitin sulfate and its salt, water-soluble chitin or chitosan derivative, pyrrolidone carboxylic acid and its salt, sodium lactate, mini sasanishiki extract Agent. For hair such as selenium disulfide, alkylisoquinolinium bromide, zinc pyrithione, biphenamine, thianthol, castari tincture, ginger tincture, red pepper tincture, quinine hydrochloride, strong aqueous ammonia, potassium bromate, sodium bromate, thioglycolic acid Agent. Antiandrogens such as follicular hormones (estrone, estradiol, ethinyl estradiol, etc.), isoflavones, oxendrone.

  Peripheral blood flow promoters such as vitamin E and its derivatives, assembly extract, garlic extract, carrot extract, aloe extract, gentian extract, toki extract, cephalanthin, carpronium chloride, minoxidil. Topical stimulants such as pepper tincture, nonyl acid vanillamide, cantalis tincture, ginger tincture, peppermint oil, l-menthol, camphor, benzyl nicotinate.

  Photoactive element 301, hinokitiol, pantothenic acid and its derivatives, allantoin, placental extract, biotin, pentadecanoic acid glycerides and the like. Antiseborrheic agents such as pyridoxine and its derivatives, sulfur and vitamin B6. Keratolytic agents such as resorcin, salicylic acid and lactic acid.

Hydrogen peroxide solution, sodium persulfate, ammonium persulfate, sodium perborate, urea peroxide, sodium percarbonate, sodium tripolyphosphate, sodium bromate, potassium bromate, sodium pyrophosphate, sodium orthophosphate Oxidants such as sodium silicate hydrogen peroxide adduct, sodium sulfate sodium chloride hydrogen peroxide adduct, β-tyrosinase enzyme solution, and mushroom extract.
Inorganic reducing agents such as strontium sulfate, sodium sulfide, barium sulfide, calcium sulfide, thioglycolic acid or its salts (calcium thioglycolate, sodium thioglycolate, lithium thioglycolate, magnesium thioglycolate, strontium thioglycolate, etc. ) And other hair removal agents. Hair swelling agents such as ethanolamine, urea, and guanidine.

  5-aminoorthocresol, 2-amino-4-nitrophenol, 2-amino-5-nitrophenol, 1-amino-4-methylaminoanthraquinone, 3,3'-iminodiphenol, 2,4-diaminophenoxyethanol hydrochloride 2,4-diaminophenol hydrochloride, toluene-2,5-diamine hydrochloride, nitroparaphenylenediamine hydrochloride, paraphenylenediamine hydrochloride, N-phenylparaphenylenediamine hydrochloride, metaphenylenediamine hydrochloride, orthoaminophenol, N-phenyl acetate Paraphenylenediamine, 1,4-diaminoanthraquinone, 2,6-diaminopyridine, 1,5-dihydroxynaphthalene, toluene-2,5-diamine, toluene-3,4-diamine, nitroparaphenylenediamine, paraaminophenol, para Nitroorthophenylenediamine, parafe Range amine, paramethylaminophenol, picramic acid, sodium picraminate, N, N′-bis (4-aminophenyl) -2,5-diamino-1,4-4-quinonediimine, 5- (2-hydroxyethylamino) ) -2-methylphenol, N-phenylparaphenylenediamine, metaaminophenol, metaphenylenediamine, 5-aminoorthocresol sulfate, 2-amino-5-nitrophenol sulfate, orthoaminophenol sulfate, orthochloroparaphenylenediamine sulfate 4,4'-diaminodiphenylamine sulfate, 2,4-diaminophenol sulfate, toluene-2,5-diamine sulfate, nitroparaphenylenediamine sulfate, paraaminophenol sulfate, paranitroorthophenylenediamine sulfate, paranitrometaphenylenediamine sulfate , Paraphenyle sulfate Diamine, paramethylaminophenol sulfate, metaaminophenol sulfate, metaphenylenediamine sulfate, catechol, diphenylamine, α-naphthol, hydroquinone, pyrogallol, phloroglucin, gallic acid, resorcin, tannic acid, 2-hydroxy-5-nitro- Dye agents such as sodium 2 ', 4'-diaminoazobenzozene-5'-sulfonate and hematein.

  Natural animal fragrances such as musk, civet, castorium, ambergris, anise 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, guayakwood essential oil, cumin essential oil, black letter Essential oil, cinnamon essential oil, cinnamon essential oil, geranium essential oil, copaiba balsam essential oil, coriandel essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, gingergrass essential oil, cedar essential oil, western mint essential oil, dairy perfume essential oil, tuberose essential oil, Clove essential oil, orange flower essential oil, winter green essential oil, trout balsam essential oil, buttery essential oil, rose essential oil, palmarosa essential oil, salmon essential oil, hiba essential oil, sandalwood essential oil, petit gren essential oil, bay essential oil, vetiva essential oil, bergamot essential oil, peruvian balsa Essential oils, bois de rose essential oil, Yoshikusunoki essential oil, mandarin essential oil, eucalyptus essential oil, lime essential oil, linaloe essential oil, lemongrass essential oil, lemon essential oil, rosemary essential oil, vegetable flavoring such as Japanese mint essential oils, perfumes and other synthetic fragrances.

  Red cabbage dye, red rice dye, red dye, anato dye, scum dye, turmeric dye, enju dye, krill dye, amber dye, caramel, gold, silver, gardenia dye, corn dye, onion dye, tamarind dye, spirulina dye, Pigments and colorants such as buckwheat whole pigment, cherry pigment, laver pigment, hibiscus pigment, grape juice pigment, marigold pigment, purple potato pigment, purple yam pigment, lac pigment and rutin.

In addition, almond (nong peach), eye (indigo leaf), blue quail (Keifu Fuji), Aotsuki rafuji (wooden moth), aonoo agave, fuchlin agave, acacia, red currant fruit, red grape, redwood (logwood), red bud (red bud), Akane (Azalea), Akajiojio Jiou (Gizo), Agi (Atsu), Akinire (Chizome), Akebiki (Kitsu), Asa (Asako Jin), Maruasaagao or Asagao (Toshigyu), Ashitaba (Tomorrow) Leaf), azuki bean (red bean), acerola, asenyaku (Asen Yaku), anise, abemaki fruit, avocado, flax, achacha (Amacha), achacharu, amadokoro (tamatake), amigasayuri (shellfish mother), Altea, Arnica, aloe (蘆薈), aloe vera, angelica, apricot honanzu (Anzujin), Ansokkou (benzoic incense), igakozolina (Gold head), Japanese knotweed (tiger cane), strawberry, Fig (no flower fruit) or its leaves, Ichibi (Winter coconut), Ichiyakuso, Ginkgo (Ginkgo leaves, Ginkgo), Japanese peas (Garden), Carob, rice seed or seed coat, Inondo seed, Ibukizasou, nettle, ylang-ylang, fennel Ayaka), Ukiyagara (Sanryo), Uguisukagura fruit, Himewikyo, Turmeric (Urban), Usubasaishin Keirinsaishin (spicy), Usbeniaoi, Usubenitachiaoi, Morayella (Summer hay), Udo or Shishido )茸), Ebisu rush (Keiko), Elderberry fruit , Elemi, Elingi (pre-lotus eringi), Enju (槐花, 槐花 米), Ogi Kibanaogi (yellow 耆), Oulen (yellow ream), Okarasuuri (Karonin), Otsu ヅ rafuji (prevention), Psyllium (car) Maeko (carrot), toucan beetle (lion), Ovana okera okera (white birch), Obayaya shabushi fruit, sea hawthorn hawthorn (Yamakoko), Ohisanoyuki, Sasanoyuki, barley (barley), oguruma (turnover), okrajin, okraine Tochiban carrot (carrot), Hypericum pertussus楡), Ominaeshi (losing sauce), Dutch strawberry, Dutch mustard (watercress), Dutch jellies, Netherlands Honey bees, olives, oregano, orange fruit or skin, coconut moth (ripening yellow), cacao seeds, oysters or their leaves (crabs), scabbard (fish), cassia, casino berries (fruits), gadgets (crabs) , Oak wrinkles, oak leaves, cascarilla, cynomolgus (Kinshato), valerian (valerian), birch or fern birch (white birch), pumpkin, kapok seeds, kahoku salamander (carp), gama (carp yellow), chamomile・ Roman chamomile, Camille deer (weed), Cam cam / duck duck, Calla cucumber (Royal moth), Crow bishak (Half summer), Oats, Garana seeds, Caraho (Park), Karaya, Karin (Kiso), Garcinia, Kawayanagi, Kawaratake, Kawara mugwort (Sardine Chin), Kansui (Sweet), Licorice (licorice), Kantara Asa, Candelilla, Kantou, Kanna, Raspberry, Kiwi Fruit, Kikaras Li (Korone), Kyokyo (Kikkyo, Kikyo Root), Chrysanthemum (Chrysanthemum flower), Kisage (Kashimi), Gishigishi (Shione), Pheasant (Kashimi), Kizuta, Kidachi Aloe, Kidachihakka, Kina, Kinanoki ), Yellowfin, yellowtail, cabbage, cabbage, unripe fruit, cucumber, Kiraja saponaria, quilla, kumquat fruit, betel, goldfish (Sentsukakusa), guava fruit, guayule, quellus infectria (garlic) , Wolfberry (bamboo shoots, coconut tree, cocoon leaf, earth bone bark), cedar kazura (Tenmon winter), camphor tree, gooseberry fruit, gardenia (mountain lion), kunugi (bamboo grass), kumazasa, pine moth (clasp grass), clara (bitter) ), Cranberry fruit, chestnut or its astringent skin, curculigo latifolia fruit, grapefruit, buckthorn, black sage Ji (Necessary), Kurobana toukikoshi, Clove (Cycho, Dingko), Keigai (Akatsuki, Ayuho), Keito (Couple flower, Chicken clover), Bay bay (Laurel tree), Kenashi Sartori Ibara (Tsumago, Mountain return), Gentiana, Gennoshouko (Old-weed grass), Kouji / Tachibana / Obenimikan / Ponkan / Santara (Tachibana bark), Koshinbara (monthly flower), Kousei mint, Kozo fruit, Kocha (tea), Kohone (river bone), Kohon (Tsubakimoto, Karasumoto) ), Koryang, Cilantro fruit, Koganebana (Yellow Gon), Cowberry (Etsutachibana), Coconut fruit, Goshuyu (Golden cucumber), Gosho strawberry (Golden bonsai), Pepper (Pepper), Copaiba balsam, Coffee beans, Kobushi magnolia ), Burdock (beef bowl, beef eggplant), coconut lees, sesame seeds (sesame seeds), sesame seeds (genus ginseng), trash (savory), sanekazura, binankazura, matsubusa, Wheat (wheat), rice / rice bran (red cocoon, white birch), rice oil, cola acuminata seeds, cola vera seeds, fenugreek fruit, colombo, condurango, kombu, konjak, comfrey (sardine grass), sisal, sisal asa Leaf, flower, fruit, and bark (cherry tree) , Cherries, pomegranates, sasa, sasanqua, sasmodaka, sweet potatoes, sugar cane, sugar beet, saffron jujube (acid sour), saffron (bansho, west safflower), pomelo fruit, savanna, salmon berry, salamander ) 、 Salvia (Sage) 、 Sagaki Kyo (Sankyo Vegetables) ), Sawagurumi (Sancho), Sanshinin carrot (37 ginseng), Sanshuyu (Yamamuro), Sansho (Yamamuro), Sandskon (Yamazune), Shea (Kalite), Cyano fruit, Shiitake mushroom (Shiitake), Sion ( Shiki), Dikitaris, Shikunshi (Amiko), Shiso, Aojiso, Chiri Menzo, Katamenjiso (Shiyo, Shiso), Rosewood, Linden, Syringae, Sylemeng (ream), Shimakaniku (Chrysanthemum flower), Shimeji (Himushiji, Shakashimeji) , Oshiroi shimeji, beech shimeji mushroom, shimotsukeso, potato, peonies (shakuyaku), shajin (shasan), janohi (barley winter), juzudama, palm fruit, ginger (ginger), ginger (root), Shozuk fruit, white-bellied seeds, white-faced butterfly seeds, white plant flowers, white minten (southern fruit), cinchonasacill La, cinnamon, watermelon (Sairan), honeysuckle (gold and silver flowers, Shinobu), sorrel (Acid), swimberry fruit, stevia, strawberry fruit, sugina (question), stevia, plum fruit, red pine cone, larch , Kizota, Prunus, Hawthorn, Dandelion, Horse Chestnut (Maronier), Pear fruit, Zodiac, Elder, Prunus, Milfoil, Rose Japanese butterfly, mistletoe, yellow mint, wild mint, horseradish, horseradish, stone radish, mallow, green sage, senega, seri, celery, nematode (river cucumber), sendan, senburi (medication), senna fruit or leaf , Ginseng (daikon), soka (grass), buckwheat seeds, potato monopods, daiou (dai yellow), radish, soybeans, daidai (orange peel, persimmon), takatodai (daikon), hawk abalone (dark spine), dark sweet cherry Fruits, hollyhock, red pepper (thyme, perilla), red willow, tamarind seeds, onion, red bean, cypress or its root bark, tanjin, dandelion or dandelion, dandelion, danmaru, cherry fruit , Chigaya or its root (Sone), Chikutsujinjin (Bamboo ginseng), Chicory, Ginseng (Gomi), Ginseng (Dahi), Ginseng (Ginseng), Ginseng (Ginseng), Ginseng (Ginseng), Choreimaitake (Tsubaki), camellia, Tsukuritake (mushroom), camellia, camellia, clover (lacquered rice cake) Grass), cypress (duck cocoon grass), vine azuki (red azuki bean), tsurudukudami (what's neck moth), tsuruna (apricot), tsuruminjin (four leaf ginseng), tsubebuki, deiko, teuchigurumi, dubery fruit, tengusa, tencha (boiled tea), tendai yak ( Glaze), Toga (Winter Lion), Pepper (Banban), Toki (Toyaki), Tokinsenka (Marigold), Corn or Corn Hair (Southern Shark), Toad Momochi (Sadako), Torindo (Ryobi) , Dokudami (10 medicines), Tokon (root), Toshishi-Mamedaoshi-Nenkakazura, Tochu (Tochu, Tochu), Tomato, Tragacanth, Triacanthus seeds, Tormentilla, Dronoki, Toro-aoi, Nigerian berry, Nagaimo yam (Medicine), nagii kada (butcher bloom), naginata koju, nazuna, rapeseed, jujube, jujube (large cicada), naniwa Rose (gold sakurako), Nameko, Naruko Yuri (yellow spirit), peanut (peanut), Nanten (southern shin), Nigaki (Nakiki), Nigorigi (Nagiki), Nikuzuku, Kay Nikkei (Kaishin), Keishi (Keishi) , Leek (lion), elderberry (bone graft) fruit / flower or stem / leaves, garlic (large coral), nurde (pentose), leek, white thistle (large coral), nobara (fruit), yarrow, nodake (maehu), Novara, Peach, Palm, Pineapple fruit, Hibiscus (Bussouge, Furinbussouge, Roselle), Hakamurabosi (Occultus), Hakusen (Shiroki), Hakuruberry fruit, Hakobe (Traditional), Hazel (Egg), Hasidorokoro (Roth root) , Basil, lotus (lotus, lotus meat, lotus), parsley (holland jellie), hadakamugi, batata, beech mushroom (bamboo bamboo), patchouli, mint (light load, light load leaf), pearl barley (yokuinin), hanasuge (knowledge) ), Banana, Hana-hakka, Vanilla Bins, Papaya, Pleurotus moth (Hagagusa), Hubgrass, Paprika, Amaranthus (Vulgaris), Hamasuge (Katsukiko), Amaranthus (Shitsuko), Hermanus (Maikai Flower), Hamaboufu (beach windbreak), hamamelis, rose (rose), agaric (agaric, white-faced agaric, Ukimorinokasa), parietaria, haruni (crustacean, cinnabar skin, coral leaf), breadfruit, lizard carrot (participant), pecan nut, ganbanana (Ishizuchi, Bujushahua), Hikikoshi (prolonged grass), Hishi (Rishimi), Pistachio, Beet, Peanut seed coat, Hitsuba (Ishizuchi), Hinata Taikozu (cow knee), Hinoki, Hiba, Castor, Sunflower, Peppers, Himegama (Kaori), Himematsutake (Kawariharatake, Hiromatsutake), pimenta fruit, peony, beakkyu, jade fruit, belode Oy, Hiroha Okinagus (bald eagle), loquat (bamboo shoots, cocoon leaves), betel nuts (large clothes, coconut leaves), bougainberea, scallops (southern rattan), baboons, dandelion (striated winter flowers, sectonic winter leaves), Fujibakama (Orchid) Fuji bean (boiled soybeans), grape fruit or pericarp / seed / leaves, beech, Fuyumushinatsutake (Cycium Cordyceps), Brazilian licorice, black currant fruit, blackberry, plum fruit, fluceraria, blueberry (Prunus japonica), prunes, blond Psyllium, bundo (mung bean), loofah, safflower (safflower), henenken, belladonna, berry fruit, pervianburg, boysenberry fruit, bowfish (windproof), spinach, physalis (Tororoot), honoki (Japanese rustic, park), Bokeh (Kiso), Hosobana Okera (Amber), Hosobabarengiku, Bodaiju (Aoki), Button (peony, peony skin) , Jojoba, white berry fruit, hon-shimeji mizzle, maize (maiko), maitake (maiko), maou (mao), macadamia nuts, macri (marine grass), mugwa (mulberry white skin, mulberry leaf), magnolia Sprengeri, Matatabi (wooden candy), Matsukasa, Matsuba, Matsuhodo (ド), Mayoram (Hanahakka), Malvano jardin (bitter), Mulberry fruit, Quince, Mango, Mangosteen, Manshugurumi, Mandarin fruit, Mannentake (Ganoderma), Citrus genus fruit (fruit berry), Mishima Saiko (Shibahu), Mizokakushi (half-sided lotus), Misohagi (Chinese cucumber), Mitsugashi, Mitsuba, Midorihakka, Mimosa, Ginger, Miracle fruit fruit, Myrrh, Milobaran, Mukge , Munoki, Mukuroji, Murasaki (purple root), Murasaki maize, Mejiki (beneficial herb), Meadowgi, Melaleuca Melissa, Melilot, Melon fruit, Moukomomogi, Mosouchiku, Mokko (wooden incense), Japanese maple leaf, Peach leaves (peach leaves) / fruits / seed (peach seeds), coconut palm, Morello cherry fruit, Morohaya (burlap), Yakawamurasakiimo , Yakuchi (Yoshichi), cornflower (cornflower), cornflower mint, yashabushi (arrow wheel), willow willow, starfish (octagonal gold plate), mistletoe (willow infestation), willow leaves, yabgarashi, yabukouji (purple gold beef), pokeweed (trade) Terrestrial), mountain alder (Yamamuro), yamamomo (Yamamushi), sagebrush, eucalyptus, yukinoshita (tiger ear grass), yucca flavifolia, yuzu fruit, lily, birch, European strawberry, mugwort (lime leaves), lime fruit, rye, Lacanca fruit, raspberry leaf / fruit, lavender, rambutan seed, ryokcha (green tea), apple fruit, gentian, Bass Suabisimus (Lyo), lettuce, red currant fruit, lemon fruit, lemongrass, forsythia, forsythia, wax palm, locon (Yoshi: Sone) Loganberry fruit, rosemary (mannenrou), rosehip ( Wild rose), longan seeds, horseradish, garlic (green soil), etc. and greens such as Chlorella vulgaris, Chlorella pyrenoidosa, Chlorella ellipsoidia, Aonori (Usubaaoori, Sugiaonori, Hiraaoori, Boaoonori, Hosoedaoriori) Kombu (Macombu, Resilibu, Hosome Kombu, Mitsuishi Kombu), Wakame, Hirome, Aowakame, Giant Kelp (Macrocystis pirifera, Macrocystis integrifolia, Neocities Ruetkeana), hijiki, hibamata Brown algae Seaweed and Chlamydomonas, Prunus serrata, Prunus serrata, Prunus cricket Hizaori, Aoumiduro, Tsurugidomiro, Hibimidoro, Anaaaosa, Amiaosa, Nagaaosa, Kawanori Fricciella, Giant puffer, Assamirishogusa, Kawashimachigusa, Marimo, Tamagobaronia, Tamavalonia, Magamata, Fusaiwata, Surichogita, Heraiwata, Kurokita, Hanemomo, Mill, Chromil, Sakibuchimiru, Nagamil, Kazumomi , Tsutsumimo, Duckweed, Hitomigusa, Hirohanohitogususa, Usuhitogusa, Motsukihitoe, Sayamidro, Kunshomo, Sumiremo, Hoshimidoro, Fuchinashimidoro, etc. , Piraela, Nagamisiomidro, Iso Grape, Isogawara, Gunsenkurogashira, Kashirazaki, Muchimo, Hihi Muchimo, Quercus cristatus, Amygusa, Sakibiro amiji, Sanadagusa, Fukurimamiji, Common gusset, Ezoyahaz, Yahazugusa, Uraboshiyahaz, Jigumigusa, Umichiwa, Kona Uchiwa, Akabumi Utsumuna, Hachimokumakuna, Sericho , Ishimozuku, Chromo, Nisemozuku, Mozuku, Ishige, Iromega, Ichimegasa, zelkova, Cyprinus, Urushigusa, Keurushigusa, Tobacco pricklyfish, Crested beetle, Habamodoki, Habanori, Habanori, Common bukuro , Squirrel, weeping manori, crayfish, fennel, vine, shark, squirrel, mi Sujikombu, Atsuba miso kumbu, Gatsugara kumbu, Kakijima kumbu, Oni kumbu, Gohei kumbu, Naga kumbu, Pea kumbu, Ojiji kumbu, Toro kumbu, Antokume, Kajime, Tsuruarame, Kurome, Kikushikikombu, Hoshikokumokui, Arashio Shiga Yabane Moku, Rappa Moku, Joromok, Hiemomoku, Tamana Moku, Iso Moku, Nagashima Moku, Akamoku, Shida Moku, Honda Walla, Nejimoku, Narasamo, Mametawara, Tatsukuri, Yatsumata Moku, Haemu Moku, Habokumoku Brown algae such as, yellow spider, blue spider Asakusa nori, Susabinori, Uppuinori, Onimanori, Tasa, Fuiritasa, Benitasa, Mirunobeni, Akebono mozuku, Hikonahada, Yogore Hanagari, Azonahadada, Umizomena, Tsukumonosahori , Tamitataki, Kaginori, Kaikekenori, Himetengusa, Hytengussa, Oobusa, Nambugusa, Kohira, Yohira, Kinukusa, Hibirodo, Himebiro, Isomumedoki, Michigaeso, Ryumonso, Nisekabokena , Shiogusagoromo, Etuki Iwakawa, Kainokawa Crabnote, coral spider, centipede, striped caddy, katanari, hiram cadet, cypress spider, cherry blossom, nikmu cadede, tanbanori, tsurutsuru, nurakusa, kuronurakusa, omkadenori, hirakintoki, matabo, chibo tsuki, swordfish , Nagaobane, Hanafnori, Ochonori, Mafonori, Karekigusa, Hosowanotosakamodoki, Hirohatosakamodoki, Yatsudegatatosakamodoki, Kurotosakamodoki, Nezanotosakamodoki, Kinohada, Ezotosaka , Usuginu, Nikohounoo, Venice Nago, Susukabebeni, Yamadagusa, Mirin, Hosobamilin, Kikutosaka, Ezonameshi Somokka, Yukari, Hosoyukari, Ibaranori, Saidaibara, Tachiibara, Kajiibaranori, Phalaenopsis, Isodantsu, Atsubanori, Ogonori, Tsurusiramo, Shiramo, Oogo-nori, Mizookonori, Birch, Azalea , Spinach, staghorn, Japanese cypress Hirohafushitsugi, Hirawatsunagisou, Usubawatsunagisou, Igis, Keigis, Rigigis, Haneigis, Amixa, Egonori, Futogigis, Saeda, Chirimomiji, Habutaenori, Konohanori, Suzushironori, Usbeni, Hasujiginu, Nagakonohanori, Sugiginu, Abassaginu, Kagiusbanori, Yasu Shimadajia, Daijimomodoki, Morayogusa, Fuyugusa, Makri, Hanayanagi, Yuna, Yanagiri, Motsureyuna, Veneer, Coriander, Prunus, Prunus, Prunus , Usbahiodo, isomegus, stinkweed, isobasho Red algae such as Fujimatsumo, Haezaki-no-kogirihiba, kawamozuku, aokawamozuku, himekamozuku, idekogome, okichimozuku, chinorimo, chisujinori, etc. Other algae such as yellow algae and chicken crown extract, cow / human placenta extract, pig / cow stomach, duodenum or intestinal extract or its degradation products, pig / cow spleen extract Or a degradation product thereof, an extract of brain tissue of pig or cow, a water-soluble collagen, a collagen derivative such as acylated collagen, a collagen hydrolyzate, elastin, an elastin hydrolyzate, a water-soluble elastin derivative, keratin and a degradation product thereof, or Their derivatives, silk proteins and their degradation products Or derivatives thereof, porcine / cow blood cell protein degradation product (globin peptide), porcine / cow hemoglobin degradation product (hemin, hematin, heme, protoheme, heme iron, etc.), milk, casein and its degradation products or derivatives thereof, Non-fat dry milk and its degradation products or derivatives thereof, lactoferrin or its degradation products, raw materials derived from animal materials such as egg components, fish degradation products, etc. are routinely performed according to the product type and form to be added Processing (for example, optional selection of grinding, milling, washing, hydrolysis, fermentation, purification, pressing, extraction, fractionation, filtration, drying, powdering, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization, etc. (Combined processing) may be performed and selected from various materials.

  The solvent used for the extraction may be selected in consideration of the processing performed later, but usually water, a water-soluble organic solvent (for example, ethanol, propylene glycol, 1,3-butylene glycol, etc.) It is desirable to use one or a mixture of two or more selected from among the above. However, when it is not preferable to contain an organic solvent depending on the application, only water may be used, or ethanol that can be easily removed after extraction may be used alone or in any mixture with water.

  Others, moisturizers, hormones, sequestering agents, pH adjusters, chelating agents, antiseptic and antibacterial agents, cooling agents, stabilizers, emulsifiers, animal and vegetable proteins and their degradation products, animals and plants Saccharides and their degradation products, animal and plant glycoproteins and their degradation products, blood flow promoters, anti-inflammatory agents, antiallergic agents, cell activators, keratolytic agents, wound treatment agents, foam enhancers, thickeners, oral cavity Additives, deodorizing / deodorizing agents, bittering agents, enzymes and the like can be raised, and in combination with these, various additive and synergistic effects can be expected.

Example 1
The puffer skin from which the attached meat was removed was cut into approximately 1 cm square. To 50 g of the obtained puffer fish skin, 1000 mL of a sodium hydroxide solution having a concentration of 0.3 mol / L was added and stirred overnight at 5 ° C. The fish skin was collected and sufficiently washed with cold water. The obtained fish skin and 500 mL of a cold sodium chloride solution having a concentration of 1 mol / L were added to a mixer and homogenized for 1 minute, and the precipitate was separated by a filtration method. This operation was repeated three more times. The resulting precipitate is washed with cold water, added to 1000 mL of water-containing ethanol (ethanol concentration 70% by weight) and stirred at 10 ° C. overnight, and the precipitate is collected by centrifugation (10000 G, 10 minutes), and again in the same manner. After the water-containing ethanol treatment was added, it was washed with water to obtain 32 g of fish skin purified precipitate. 30 g of the resulting mahugu fish skin purified precipitate was added to 600 mL of an aqueous citric acid solution having a concentration of 0.03 mol / L, followed by stirring and extraction at 5 ° C. for 24 hours. The resulting collagen solution was separated and removed by centrifugal separation to obtain a collagen solution. The obtained collagen solution was diluted with a 0.03 mol / L citric acid solution to obtain a 0.3% concentration collagen solution.

Comparative Example 1
The puffer skin from which the attached meat was removed was cut into approximately 1 cm square. To 50 g of the obtained puffer fish skin, 500 mL of a cold sodium chloride solution having a concentration of 1 mol / L was added to a mixer and homogenized for 1 minute, and the precipitate was separated by a filtration method. This operation was repeated three more times and then washed with cold water. 30 g of the resulting purified pufferfish skin precipitate was added to 600 mL of an aqueous citric acid solution having a concentration of 0.03 mol / L, followed by stirring and extraction at 5 ° C. for 24 hours. The resulting collagen solution was separated and removed by centrifugal separation to obtain a collagen solution. The obtained collagen solution was diluted with a 0.03 mol / L citric acid solution to obtain a 0.3% concentration collagen solution.

(Certification)
The collagen solutions obtained in Example 1 and Comparative Example 1 were freeze-dried, and the pufferfish toxin was quantified according to Chapter 7 Mouse Assay in Food Sanitation Inspection Guidelines RIKEN (Ministry of Health, Labor and Welfare, 2005). As a result, as shown in Table 1, the pufferfish fish skin-derived collagen prepared in Comparative Example 1 showed pufferfish poison, but the pufferfish fish skin-derived collagen prepared in Example 1 including an alkali treatment and a hydrous alcohol treatment operation was used. It has become clear that has been detoxified.

Example 2
The trough puffer skin from which the attached meat was removed was cut into approximately 1 cm square. To 50 g of the obtained puffer fish skin, 1000 mL of a sodium hydroxide solution having a concentration of 0.2 mol / L was added and stirred overnight at 5 ° C. The skin was collected and sufficiently washed with cold water. The obtained white skin and 500 mL of cold sodium chloride solution having a concentration of 1 mol / L were added to the mixer and homogenized for 1 minute, and the precipitate was separated by filtration. This operation was repeated three more times. The obtained precipitate is washed with cold water, added to 1000 mL of hydrous ethanol (ethanol concentration 70% by weight) and stirred overnight at 10 ° C., and the precipitate is collected by centrifugation (10000 G, 10 minutes), and again hydrous After adding ethanol treatment, it was washed with water to obtain 21 g of a puffer fish skin purified precipitate. 20 g of the obtained puffer fish skin purified precipitate was added to 800 mL of an aqueous citric acid solution having a concentration of 0.03 mol / L and stirred at 5 ° C. for 1 hour. Then, 0.23 g of pepsin was added and the mixture was further extracted by stirring for 24 hours. Thereafter, the pH was adjusted to 10 using a dilute aqueous sodium hydroxide solution, and the mixture was stirred at 5 ° C. for 24 hours to inactivate pepsin. To the obtained atelocollagen solution, 2.5 g of succinic anhydride was added and reacted at 5 ° C. while adjusting the pH to 9-12 using a sodium hydroxide solution. After completion of the reaction, the pH of the solution was adjusted to pH 4.5 using dilute hydrochloric acid, succinylated atelocollagen was precipitated, recovered by centrifugation (10000 G, 20 minutes), and then washed with 50% ethanol. It was dissolved in a 0.03 mol / L phosphate buffer solution (pH 6.0) to a concentration of 0.3% to obtain a puffer fish skin-derived succinylated atelocollagen solution.

Comparative Example 2
A succinylated atelocollagen solution was prepared in the same manner as in Example 2 using tilapia fish skin instead of trough.
Comparative Example 3
A salmon fish skin was used instead of trough and the same operation as in Example 2 was performed to prepare a succinylated atelocollagen solution.
The moisture retention of the obtained various fish skin-derived succinylated atelocollagens was compared.
Various fish skin-derived succinylated atelocollagen solutions were applied to the subject's forearm, and the water content after 2 hours was measured using an epidermis stratum corneum moisture measuring device (SKICON 200, manufactured by IBS Co., Ltd.). The results are shown in Table 2. In the treatment group to which succinylated atelocollagen derived from puffer fish skin was applied, the conductance value was clearly larger than that in the treatment group to which succinylated atelocollagen derived from other fish skin was applied, and a clear moisturizing effect was observed.

Example 3
The adhering meat was removed, and the skin of the crow fugu from which the epidermis and spines were removed by skinning was cut into approximately 1 cm square. To 50 g of the obtained puffer fish skin, 1000 mL of a potassium hydroxide solution having a concentration of 0.2 mol / L was added and stirred overnight at 5 ° C. The skin was collected and sufficiently washed with cold water, and then the obtained skin and 500 mL of a cold sodium chloride solution having a concentration of 1 mol / L were added to a mixer and homogenized for 1 minute, and the precipitate was separated by filtration. This operation was repeated three more times. The resulting precipitate is washed with cold water, added to 1000 mL of water-containing ethanol (ethanol concentration 70% by weight) and stirred at 10 ° C. overnight, and the precipitate is collected by centrifugation (10000 G, 10 minutes), and again in the same manner. After the water-containing ethanol treatment was added, the product was washed with water to obtain 31 g of a puffer fish skin purified precipitate. 30 g of the obtained puffer fish skin purified precipitate was added to 600 mL of an aqueous citric acid solution having a concentration of 0.03 mol / L, stirred at 5 ° C. for 1 hour, then added with 0.16 g of pepsin, and further extracted by stirring at 5 ° C. for 24 hours. Thereafter, the pH was adjusted to 10 using a dilute aqueous sodium hydroxide solution, and the mixture was stirred at 5 ° C. for 24 hours to inactivate pepsin. From the obtained solution, the insoluble matter was separated and removed by a centrifugal separation method to obtain an atelocollagen solution. The obtained atelocollagen solution was dropped into 20% hydrous isopropyl alcohol and precipitated. The obtained precipitate was sufficiently washed with the same 20% aqueous isopropyl alcohol, and then washed with a dilute aqueous sodium hydroxide solution (pH 8.0), and the precipitate was collected by centrifugation. After dispersing the obtained atelocollagen precipitate in water, add citric acid to a concentration of 0.03 mol / L and stir overnight at 5 ° C. to dissolve the atelocollagen to obtain a 0.3% concentration oat collagen derived atlas collagen solution It was.

Example 4
After removing the attached meat and performing skinning, the cuttlefish skin from which the epidermis was removed was cut into approximately 1 cm square. To 50 g of the obtained puffer fish skin, 1000 mL of a sodium hydroxide solution having a concentration of 0.25 mol / L was added and stirred overnight at 5 ° C. After recovering the skin and washing it thoroughly with cold water, add 500 mL of the obtained skin and 1 mL / L of cold sodium chloride solution to the mixer, homogenize for 1 minute, and centrifuge the precipitate (10000 G, 10 minutes) ). This operation was repeated three more times. The resulting precipitate is washed with cold water, added to 1000 mL of hydrous methanol (methanol concentration 85% by weight) and stirred overnight at 10 ° C., and the precipitate is collected by centrifugation (10000 G, 10 minutes), and again hydrous After the methanol treatment, washing with water was performed to obtain 30 g of a puffer fish skin purified precipitate. After adding 600 g of 0.03 mol / L citric acid aqueous solution to 30 g of puffer fish skin purified precipitate and stirring at 5 ° C. for 1 hour, 0.17 g of pepsin was added and the mixture was further extracted by stirring for 24 hours. Thereafter, the pH was adjusted to 10 using a dilute aqueous sodium hydroxide solution, and the mixture was stirred at 5 ° C. for 24 hours to inactivate pepsin. 30 mmol of maleic anhydride was added to the obtained atelocollagen solution and reacted at 5 ° C. while adjusting the pH to 9-12 using a dilute aqueous sodium hydroxide solution. After completion of the reaction, the pH of the solution was adjusted to pH 4.2 with dilute hydrochloric acid to precipitate maleated atelocollagen, recovered by centrifugation (10000 G, 20 minutes), and then washed with 50% ethanol. The recovered precipitate was dissolved in a 0.05 mol / L phosphate buffer solution (pH 6.0) so that the maleated atelocollagen concentration was 0.3% to obtain a maleated atelocollagen solution. The maleation rate (relative to εNH ₂ of collagen) by the TNBS method was 78%.

Example 5
<Manufacture of lotion>
According to the formulation shown in Table 3, (1) to (10) were stirred and dissolved to obtain a lotion. All of the obtained lotions were clear and stable without causing cloudiness for 3 months under the conditions of 40 ° C. and RH 75%.
For these lotions, a sensory test was conducted by 10 expert panelists. The evaluation was carried out in five grades for the following items.

(1) Moist skin 1. 1. It becomes bulky. Slightly soft 3. Normal 4. Slightly moist 5. Moist

(2) Skin smoothness 1. Rough Slightly rough 3. Normal 4. Slightly smooth Smooth

(3) Skin stickiness 1. Sticky Slightly sticky 3. Normal 4. Slightly refreshing 5. Table 4 shows the average score of 10 panelists.

  As is apparent from Table 4, the product of Example 5 containing succinylated atelocollagen derived from puffer fish skin was succinylated from salmon fish skin of Comparative Example 4 and succinylated atelocollagen derived from tilapia fish skin of Comparative Example 4. It showed better moisture retention and skin smoothness than those containing atelocollagen.

Example 6
<Manufacture of shampoo>
According to the formulation shown in Table 5, (1) to (4) and (6) to (8) were mixed and stirred at 70 ° C and cooled to 30 ° C, then (5) was added and mixed and stirred to prepare a shampoo agent. Obtained. When the resulting product was used to wash the hair, the hair feel was smooth and moisturized.

Example 7
<Manufacture of cream>
According to the prescription shown in Table 6, (8), (10), (11), and (12) were mixed and stirred at 80 ° C separately to (1) to (7) mixed and stirred at 80 ° C. Homogenized, cooled to 30 ° C. with stirring, further added (9), mixed and stirred to obtain a cream. The obtained product was not sticky during use and moistened the skin.

Example 8
<Manufacture of body gel>
According to the formulation shown in Table 7, (1) to (8) were mixed and stirred at 80 ° C. to obtain a body gel agent. The obtained product was not sticky during use and moistened the skin.

Example 9
<Manufacture of packs>
According to the formulation shown in Table 8, (1) to (2) were mixed and stirred at 80 ° C, and (3) to (13) were mixed and stirred at 80 ° C, and then mixed and stirred at 80 ° C. Then, (14) and (15) were further added and mixed and stirred to obtain a hair pack agent. When the hair treatment was performed using the obtained product, the hair was smooth and moisturized.

Example 10
<Manufacture of serum>
According to the formulation shown in Table 9, (1) to (3) were stirred and dissolved to obtain a cosmetic liquid. All of the obtained lotions were colorless and transparent, and were not sticky during use, and moisturized the skin.

The present invention relates to a collagen and / or collagen derivative derived from puffer fish fish skin in which puffer poison is detoxified, and can be used for cosmetics, pharmaceuticals, quasi-drugs, and the like.

Claims (1)

Obtained by subjecting fish skin of one or more puffer fish selected from the pufferfish genus Trafugu and Pufferfish to the alkali treatment and hydrous ethanol treatment at 10 ° C or lower using hydroxide. Furthermore, a moisturizing agent containing an atherosylated and succinylated derivative of collagen derived from puffer fish skin that has been detoxified.