JP6174854B2 - Bluefin tuna skin-derived atelocollagen and / or derivative thereof and method for producing the same, and cosmetics containing the atelocollagen and / or derivative thereof - Google Patents

Description

  The present invention relates to atelocollagen and / or atelocollagen derivative having a reduced pigment content derived from bluefin tuna skin, a method for producing the same, and a cosmetic comprising the atelocollagen and / or atelocollagen derivative.

  Collagen is a major protein that forms the skin of animals such as cow skin, pig skin, and fish skin. Collagen has been widely used as a raw material for cosmetics because it has high moisturizing properties and imparts a smooth feel to the skin. Moreover, since they have excellent biocompatibility, they are also used for pharmaceuticals and medical devices. Furthermore, in recent years, it has come to be used as a health food material for the purpose of beauty. Collagen has a telopeptide, and most of the immunoreactivity exists in this telopeptide portion. Therefore, atelocollagen in which the telopeptide portion is usually removed and the antigenicity is significantly reduced is used. Collagen that has been used in this way has mainly been made from cow skin and pig skin, but in recent years, infectious diseases such as mad cow disease and foot-and-mouth disease have occurred, and safety has been a problem. Under these circumstances, collagen other than mammals has been actively developed for new functions as well as safety. Among them, fish skin-derived atelocollagen and atelocollagen derivatives are also partly used, but they are reddish purple or grayish red, and when used at a high concentration, cosmetics will have a fish skin-derived color, There was a drawback that the usable field was narrow.

  In conventional collagen obtained from marine products, for example, collagen obtained from fish skin has low product purity and has a fishy smell, so that it is subjected to mechanical pre-processing, mixing, and washing steps to solve it A method (JP-A-5-202097) and a method through an organic solvent treatment and a high-speed centrifugation process (JP-A-2000-256398) have been disclosed. It cannot be removed. This is because, firstly, it is difficult to remove the epidermis where the pigment is present from the raw fish skin, and secondly, the pigment is dissolved in the collagen solution during the enzyme treatment during the production of atelocollagen and derivatives. It is done. In addition, it is extremely difficult to remove the dye from the atelocollagen and derivatives with the dye remaining prepared by a conventional method, and even if a method using activated carbon or ion exchange resin generally used for decolorization is carried out The pigment cannot be removed.

In addition, there is a method in which the raw material skin is bleached in advance using hydrogen peroxide or the like, but the solubility of collagen becomes extremely poor, and collagen may not be recovered at all depending on the bleaching conditions. Therefore, in order to effectively use collagen derived from marine products, development of collagen with reduced pigment and a method for producing the same is strongly desired.
Similarly, atelocollagen and derivatives derived from bluefin tuna skin, the pigment present in the skin is eluted in the product during collagen production, and only a colored collagen solution is obtained, and no collagen solution with reduced pigment is obtained. . However, since atelocollagen and atelocollagen derivatives derived from bluefin tuna skin show excellent feel and moisture retention when formulated as cosmetics, development of collagen with reduced pigments and a method for producing the same is strongly desired.
Japanese Patent Laid-Open No. 5-202097 JP 2000-256398 A

  The subject of this invention is providing the cosmetics which mix | blend the bluefin tuna origin atelocollagen and / or atelocollagen derivative with which the pigment was reduced.

  As a result of intensive studies to achieve the above object, the present inventors have used fish skin without freezing, and studied removal of the epidermis and alkali treatment, resulting in a bluefin tuna with greatly reduced pigment. It has been found that atelocollagen and / or atelocollagen derivative can be obtained. Moreover, it discovered that the cosmetics which mix | blended this atelocollagen and / or atelocollagen derivative had high moisture retention and a touch, and came to complete this invention.

That is, the present invention provides (1) atelocollagen derived from bluefin tuna skin and / or a derivative thereof, wherein the pigment content is reduced,
(2) Atelocollagen and / or a derivative thereof according to (1) obtained by removing the pigment by combining the baking soda treatment and the alkali treatment using the bluefin tuna skin without freezing,
(3) The atelocollagen derivative according to (1) to (2), wherein the atelocollagen derivative is an acylated derivative,
(4) The atelocollagen derivative of (1) to (3), wherein the acylated derivative is a succinyl derivative,
(5) A method for producing bluefin tuna skin-derived atelocollagen and / or a derivative thereof, wherein the pigment content is reduced,
(6) Atelocollagen and / or a derivative thereof obtained by removing the pigment by combining bluefin tuna skin without freezing and combining sodium bicarbonate treatment and alkali treatment,
(7) The method for producing an atelocollagen derivative according to (5) to (6), wherein the atelocollagen derivative is an acylated derivative,
(8) The method for producing atelocollagen and / or a derivative thereof according to (5) to (7), wherein the acylated derivative is a succinylated derivative,
(9) Cosmetics characterized by blending bluefin tuna skin-derived atelocollagen and / or derivatives thereof with reduced pigment content,
(10) Cosmetics according to (9), characterized in that bluefin tuna skin is used without freezing, and atelocollagen and / or derivatives thereof obtained by removing pigments by combining sodium bicarbonate treatment and alkali treatment are blended ,
(11) The cosmetic material according to (9) to (10), wherein the atelocollagen derivative is an acylated derivative,
(12) The cosmetic according to (9) to (11), wherein the acylated derivative is a succinylated derivative.

  According to the present invention, collagen derived from bluefin tuna skin with reduced pigments can be obtained, which can be effectively used in cosmetics, and excellent skin smoothness and moisture retention can be obtained.

  The atelocollagen 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 atelocollagen derivative of the present invention include acylated derivatives and alkylated derivatives. Any derivative may be used as long as it is neutral and dissolves in water. Among acylated fish skin-derived atelocollagens, acylated atelocollagens such as succinylated atelocollagen, phthalated atelocollagen, and maleylated atelocollagen and their salts are neutral and soluble in water, so they can be dissolved in pure water. Although it is possible, 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.

  The method of reducing the pigment can be achieved by using the raw skin as a raw material without freezing it, removing the epidermis with a baking soda treatment, and further carrying out an alkali treatment.

  That is, since the skin is usually frozen after catching, the freezing period is long, but it is good to eliminate or extremely shorten it. Next, the skin is swollen by immersing in sodium bicarbonate, and then the skin is physically removed. The baking soda concentration is 0.01% to 50%, preferably 0.1 to 10%. For physical removal, an appropriate tool such as a knife or a knife is used. 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 dye is reduced and the yield can be secured, but it is preferable to use an aqueous hydroxide solution having a concentration of 0.01 mol / L to 0.4 mol / L, more preferably 0.05 mol. This is an aqueous hydroxide solution having a concentration of / L to 0.2 mol / L. The temperature during 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. The obtained bluefin tuna skin with a reduced amount of pigment 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 bluefin tuna 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 glycol , Glycols such as polyethylene glycol, aromatic organic compounds such as benzene, toluene, xylene, and other organic solvents such as N, N-dimethylformamide, dimethyl sulfoxide, N, N-dimethylacetamide Either liquid or, after the organic solvent treatment with a mixed solution of these organic solvents with water, can be implemented as needed a step of centrifugation.

The obtained bluefin tuna skin is acid-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, is treated with acidic protease such as pepsin to obtain atelocollagen. That is, dilute acetic acid solution with a concentration of 0.01 mol / L to 2 mol / L, dilute lactic acid solution with a concentration of 0.001 mol / L to 2 mol / L, dilute citric acid solution with a concentration of 0.001 mol / L to 2 mol / L, 0.001
Add the bluefin tuna skin from which pigments and impurities have been removed to acid solutions such as dilute hydrochloric acid solution with a concentration of mol / L to 0.2 mol / L and dilute phosphoric acid solution with a concentration of 0.001 mol / L to 0.5 mol / L, and then add acidic protease. In addition, atelocollagen is extracted by stirring at 10 ° C. or lower, preferably 2 to 8 ° C., for 1 to 240 hours, preferably 24 to 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%.

  When the insoluble matter remains in the extracted atelocollagen solution, it is desirable to remove the insoluble matter by filtration or centrifugation. Since the obtained atelocollagen is dissolved in an acid solution, it can be used as it is, but is preferably further purified. That is, atelocollagen is precipitated by precipitating atelocollagen by salting-out method in which salt is added to atelocollagen solution for precipitation, organic solvent precipitation method in which organic solvent is added, or isoelectric point precipitation method in which base is added, and the generated precipitate is separated. Is purified. As a separation method, if a centrifugal separation method is employed, it is effective for removing odors. The salt used for the salting-out method can be any salt that precipitates atelocollagen, 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 an atelocollagen 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 atelocollagen derivative of the present invention can be easily obtained by chemically modifying atelocollagen obtained from bluefin tuna skin by a conventional method by the method described above. 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 to 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 bluefin tuna skin-derived atelocollagen or a derivative thereof according to the present invention can be used in various fields such as pharmaceuticals, medical devices, cosmetics, and foods. Cosmetics containing blue-tuna skin-derived atelocollagen or its derivatives with reduced pigments include skin lotions, milky lotions, cosmetics, basic cosmetics such as general creams, facial cleansers such as cleansing creams, packs, shaving creams, sunburns Cream, sunscreen cream, sunscreen lotion, sunscreen lotion, cosmetic soap, foundation, funny, powder, lipstick, lip balm, eyeliner, eye cream, eye shadow, mascara, bath cosmetic, shampoo, rinse, hair dye, hair It can be used for various cosmetics such as cosmetics. The blending amount is not particularly limited, but can be used in the cosmetic composition at about 0.001 to 100%, preferably 0.01% to 45%, 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 luffy oil, sesame oil, cocoa butter, chamomile oil, carrot oil, cucumber oil, beef fat fatty acid, cucumber nut oil, 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, peony (stone root), mallow, white-spotted moth, senega, seri, celery, senkyu (river cucumber), sendan, senburi (medicated), 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.

EXAMPLES Hereinafter, although an Example demonstrates this invention, this invention is not limited by this Example.

Example 1
The adhering meat was removed from the non-frozen fish skin, and the skin was further immersed in a baking soda solution overnight, and the bluefin tuna skin removed with a knife was cut into approximately 1 cm square. To 50 g of the obtained bluefin tuna skin, 1 L of a sodium hydroxide solution having a concentration of 0.1 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 was washed with cold water, then added to 1000 mL of ethanol and stirred overnight at 10 ° C., and the precipitate was collected by centrifugation (10000 G, 10 minutes). After ethanol treatment again, it was washed with water. Thus, 31 g of bluefin tuna skin purified precipitate was obtained. 30 g of the resulting purified bluefin tuna skin 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 0.17 g of pepsin, and 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. The obtained atelocollagen solution was added dropwise to 20% hydrous isopropyl alcohol to cause precipitation. 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 atelocollagen, and add 0.3% concentration of bluefin tuna skin-derived atelocollagen solution. Obtained.

Comparative Example 1
The bluefin tuna skin used in Example 1 was frozen for 1 month, and the same operation was performed without performing the pigment removal step by baking soda / alkali treatment to prepare a bluefin tuna skin-derived atelocollagen solution with a concentration of 0.3%. The degree of coloration of the obtained atelocollagen solution was determined by measuring the absorbance at a wavelength of 550 nm using a spectrophotometer. Table 1 shows the results.

As is clear from Table 1, the color of the atelocollagen of Example 1 was lower than that of Comparative Example 1.

Example 2
The adhering meat was removed from the non-frozen fish skin, and the skin was further immersed in a baking soda solution overnight, and the bluefin tuna skin removed with a knife was cut into approximately 1 cm square. To 50 g of the obtained bluefin tuna skin, 1 L of a sodium hydroxide solution having a concentration of 0.1 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 was washed with cold water, then added to 1000 mL of ethanol and stirred overnight at 10 ° C., and the precipitate was collected by centrifugation (10000 G, 10 minutes). After ethanol treatment again, it was washed with water. 20 g of purified bluefin tuna skin precipitate was obtained. 20 g of the resulting purified bluefin tuna skin 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 with dilute hydrochloric acid to precipitate succinylated atelocollagen, recovered by centrifugation (10000 G, 20 minutes), and then washed with 50% ethanol. A succinylated atelocollagen solution was obtained by dissolving in a 0.03 mol / L phosphate buffer solution (pH 6.0) to a concentration of 0.3%.

Comparative Example 2
The bluefin tuna skin used in Example 2 was frozen for one month, and the same operation was performed without performing pigment removal by baking soda / alkali treatment to prepare a succinylated atelocollagen solution.

Comparative Example 3
Using the bluefin tuna skin used in Example 2, the same operation was performed without carrying out the baking soda treatment to prepare a succinylated atelocollagen solution.

Comparative Example 4
Using the bluefin tuna skin used in Example 2, an alkali treatment was not performed, and the same operation was performed to prepare a succinylated atelocollagen solution.
The degree of coloration of the obtained collagen was determined by measuring the absorbance at a wavelength of 550 nm using a spectrophotometer. Table 2 shows the results.

  As is clear from Table 2, the succinylated atelocollagen in which all the pigment removal steps of the present invention were carried out had a markedly reduced degree of coloring compared to the comparative example.

Example 3
Meat adhering to the fish skin that had not been frozen was removed, the resulting skin was immersed in a sodium bicarbonate solution, and the bluefin tuna skin from which the pigment layer had been removed with a knife was washed with water and cut into approximately 1 cm squares. To 50 g of the obtained bluefin tuna skin, 1 L of a sodium hydroxide solution having a concentration of 0.05 mol / L was added and stirred overnight at 5 ° C. After collecting the skin and washing it thoroughly with cold water, add 50 g of the obtained white bluefin tuna skin and 500 mL of cold sodium chloride solution at a concentration of 1 mol / L to the mixer, homogenize for 1 minute, and centrifuge the precipitate ( 10000G, 10 minutes). This operation was repeated three more times. The obtained precipitate was washed with cold water, then added to 1000 mL of ethanol and stirred overnight at 10 ° C., and the precipitate was collected by centrifugation (10000 G, 10 minutes). After ethanol treatment again, it was washed with water. Thus, 30 g of bluefin tuna skin purified precipitate was obtained. After adding 600 g of 0.03 mol / L aqueous citric acid solution with 30 g of purified bluefin tuna skin precipitate and stirring at 5 ° C. for 1 hour, 0.17 g of pepsin was added and the mixture was further extracted with 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 by TNBS method (relative to εNH ₂ of collagen) was 77%.

Example 4
<Manufacture of lotion>
According to the formulation shown in Table 3, (1) to (10) were stirred and dissolved to obtain the skin lotion of Example 4. All of the obtained lotions were clear and stable without causing cloudiness for 3 months under the conditions of 40 ° C. and RH 75%. A lotion was prepared in the same manner as in the above-mentioned product except that the bluefin tuna skin-derived succinylated atelocollagen was not added.
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 clear from Table 4, the product of Example 4 containing succinylated atelocollagen showed better moisture retention and skin smoothness than Comparative Example 5 without succinylated atelocollagen.

Example 5
<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. A lotion was prepared in the same manner as in the above-mentioned product except that no bluefin tuna skin-derived atelocollagen was added.
The obtained product was used to wash the hair, and a sensory test was conducted by 55 women. Evaluation was carried out in three grades for the following items.

(1) Hair feel I'm stiff 2. Normal 3. Smooth

(2) Moisturizing hair 1. Moisture decreases No change3. Table 6 shows the average scores of 55 subjects who feel moist.

As is apparent from Table 6, the product of Example 5 containing succinylated atelocollagen showed better hair feel and moisture than Comparative Example 6 without succinylated atelocollagen.

Example 6
<Manufacture of cream>
According to the formulation shown in Table 7, (8), (10), and (11) were mixed and stirred at 80 ° C separately to those prepared by mixing and stirring (1) to (7) at 80 ° C, and then homogenized and stirred. While cooling to 30 ° C., (9) was further added and mixed and stirred to obtain a cream. A lotion was prepared in the same manner as in the above-mentioned product except that the bluefin tuna skin-derived succinylated atelocollagen was not added.
The obtained product was applied to the skin and subjected to a sensory test by 45 women. 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. The average score of 45 moist subjects is shown in Table 8.

As apparent from Table 8, the product of Example 6 containing succinylated atelocollagen moisturized the skin of Comparative Example 7 without succinylated atelocollagen.

Example 7
<Manufacture of hair packs>
According to the formulation shown in Table 9, (1) to (2) were mixed and stirred at 80 ° C., and (3), (4), (5), (7), (8), (10), ( 11) was mixed and stirred at 80 ° C. and stirred. While cooling and mixing, (6), (9), (12) and (13) were further added and mixed and stirred to obtain a hair pack agent. A hair pack was prepared in the same manner as the above-described product except that no tuna skin-derived atelocollagen was added, and this was designated as Comparative Example 8.
The obtained product was applied to the hair and a sensory test was conducted by 50 women. Evaluation was carried out in three grades for the following items.

(1) Hair feel I'm stiff 2. Normal 3. Smooth

(2) Moisturizing hair 1. Moisture decreases No change3. Table 10 shows the average score of 50 subjects who feel moist.

As is apparent from Table 10, the product of Example 7 formulated with atelocollagen showed a hair feel and moisture superior to that of Comparative Example 8 containing no atelocollagen.

Example 8
<Manufacture of milky lotion>
According to the formulation shown in Table 11, (6) was added to (11) and mixed and stirred at 70 ° C., then (1) to (5) were separately heated and dissolved, and (7), (8), (10) were In addition, the mixture adjusted to 70 ° C. was added and stirred, and (9) was added while cooling and mixing, and the mixture was stirred to obtain an emulsion. Further, a milky lotion was prepared in the same manner as in the above-described product except that no bluefin tuna skin-derived atelocollagen was added.
The obtained product was applied to the skin and subjected to a sensory test by 50 women. 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. Table 9 shows the average score of 50 moist subjects.

As is apparent from Table 12, the product of Example 8 containing atelocollagen moistened the skin more than that of Comparative Example 9 containing no atelocollagen.

The present invention relates to bluefin tuna skin-derived atelocollagen and / or atelocollagen derivative with a reduced pigment content, and can be used for cosmetics, pharmaceuticals, quasi-drugs, and the like.

Claims (6)

It is derived from baking soda dipping treatment and hydroxides alkali-treated white tuna skin, and wherein the pigment content is reduced relative to a control from untreated bluefin tuna Skin, atelopeptide collagen and / or An acylated derivative or alkyl derivative thereof . Atelocollagen and / or the acyl derivatives or alkyl derivative according to claim 1 Symbol placement, wherein the acylating derivative is succinyl derivative. A cosmetic comprising atelocollagen according to claim 1 or 2 and / or an acylated derivative or alkyl derivative thereof. After immersing the bluefin tuna skin in baking soda to swell the epidermis, physically removing the epidermis, followed by alkali treatment of the bluefin tuna skin with hydroxide, derived from untreated bluefin tuna skin A method for producing bluefin tuna skin-derived atelocollagen and / or acylated derivatives or alkyl derivatives thereof , wherein the pigment content is reduced relative to a control . The method for producing atelocollagen and / or acylated derivative or alkyl derivative thereof according to claim 4, wherein the acylated derivative is a succinylated derivative. 6. Obtaining atelocollagen derived from bluefin tuna skin and / or acylated derivative or alkyl derivative thereof by the method according to claim 4 or 5, and blending the atelocollagen and / or acylated derivative or alkyl derivative thereof to obtain a cosmetic The manufacturing method of cosmetics including this.