JPH10167924A - Melanogenesis promoting agent containing chitosan derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject promoting agent effective for promoting the melanogenesis, having high safety and enabling the prevention of gray hair, etc., by using a specific chitosan derivative as a component. SOLUTION: This promoting agent contains a chitosan derivative produced by the reaction of (A) chitosan with (B) a suctar having reducing terminal (e.g. aldose). The agent is preferably produced by forming an amide bond between the 2amino group of a glucosamine constituting the component A and the sugar having isolated carboxyl terminal and/or a sugar having isolated carboxyl terminal in the molecule obtained by the ring-opening of the component B with sodium cyanohydroborate, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel melanin production promoter containing a chitosan derivative obtained by reacting chitosan with a saccharide having a reducing terminal, and an application thereof.

[0002] The field of application can be used in all kinds of external preparations (including preparations for animals). Specifically, capsules, powders, granules, solids, liquids,
Gel or foamy 1) pharmaceuticals, 2) quasi-drugs, 3)
Topical or systemic skin cosmetics, 4) Medicinal and / or cosmetic preparations applied to the scalp / hair (eg, shampoos, rinses, treatments, permanent solutions, hair dyes, hair dressings, hair tonics) , Hair growth and hair restoration, etc.), 5) bath agents used in bath water, 6) other deodorants and deodorants, sanitary articles, sanitary cotton, wet tissues, etc.

[0003]

2. Description of the Related Art Factors that determine human skin color include the amount of melanin in the epidermis, blood flow in capillaries, pigments derived from food (carotene), and the thickness of the stratum corneum. One of the important factors is melanin pigment.

[0004] This melanin pigment is produced by melanosomes, which are organelles in pigment cells (melanocytes) present in the basal layer of the epidermis, the hair root, and the outer root sheath. In the process of melanin production, tyrosinase is activated by tyrosine in pigment cells (melanocytes) to oxidize tyrosine,
It is converted to dopa and dopaquinone, further autoxidized, polymerized via dopachrome and 5,6-dihydroxyindole, and finally turned into a melanin pigment. The melanin produced is secreted by the dendrites of pigment cells (melanocytes) into basal cells, which divide and rise as spinous cells, reach the stratum corneum, and then fall off as the stratum corneum detaches. Go.

Accordingly, melanin is found in vertebrate skin, hair,
Exists as the main pigment (color) of fur and feathers, and the deposition of melanin pigment is the main mechanism of normal color development of skin and hair, and protects the living body from ultraviolet damage caused by sunlight and other light sources. It is.

However, when human skin is exposed to ultraviolet rays for a long period of time, erythema, edema, hives, spots (spots), sparrow eggs (sobacas) and aging of the skin (skin atrophy, wrinkles, dry skin symptoms) It is well known that short-term and long-term adverse effects on health, such as the risk of skin pigmentation, senile pigmentation, melasma, and skin cancer, are also known. In addition, Caucasians and the like are susceptible to sun-induced skin cancer and have a high risk of melanoma (skin cancer). Even if a person is colored, long-term exposure to sunlight increases the risk of skin cancer and accelerated skin aging.

[0007] In recent years, some young people have a tendency to prefer a tanned skin color. As a method, natural light in a limited range (a suntan area) or a specially designed ultraviolet light source is used. Ingenuity has been made.

[0008] In the case of Japanese hair, black or brown hair is considered to be preferable, but white hair often appears as a result of aging. This is because melanin is remarkably reduced due to a decrease in the number and activity of melanocytes present in the hair bulb and the like, and this cannot be said to be cosmetically and psychologically favorable.

[0009]

If melanin synthesis could be increased and promoted in some way, the skin could be darkened without the danger of excessive UV irradiation. In addition, it is possible to prevent graying of hair.

Therefore, the present inventors have studied various natural extracts for those which have an action of promoting melanin production and are safe, and have been studying new substances and their actions. .

[0011]

Means for Solving the Problems In other words, the present inventors searched for a substance meeting the above circumstances, and reacted with a saccharide having a reducing terminal using chitosan or a low molecular weight chitosan. The obtained chitosan derivative was confirmed to have an effect of promoting melanin production, and was found to be applicable to skin cosmetics and hair cosmetics, and was found to be safe and extremely effective, and completed the present invention. did. Hereinafter, the process leading to the present invention will be described.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION The chitosan of the present invention, the saccharide having a reducing end, the production method, and the like are described below, but are not limited thereto.

The chitosan of the present invention is usually obtained by deacetylating chitin obtained from crustacean or shrimp shells by alkali treatment, enzymatic treatment, etc., and the degree of deacetylation is not particularly limited. Those having a degree of 50% or more are preferred.

The low molecular weight chitosan can be obtained, for example, by treating chitosan with concentrated hydrochloric acid or chlorine gas, sodium perborate or hydrogen peroxide, or by treating chitin with an acid or alkali and deacetylating the glycoside at the same time. It may be obtained by a method of decomposing or a method of hydrolyzing with an enzyme such as chitinase.

Examples of the saccharide having a reducing end include aldoses and ketoses such as glucose, galactose,
Monosaccharides include mannose, arabinose, xylose, erythrose and glyceraldehyde, heptulose, hexulose, pentulose, and amino sugars such as glucosamine, N-acetylglucosamine and galactosamine, deoxy sugars and branched sugars. In addition, natural sugars such as disaccharides to polysaccharides containing these monosaccharides as components, such as maltose, isomaltose, maltotriose, lactose or various oligosaccharides, pullulan, inulin, amylose, amylopectin, dextran, dextrin, and starch. And their decomposed products, isomerized products,
Derivatives (such as induction of COOH grouping) are mentioned, and one or more of these saccharides can be used in the reaction.

The chitosan derivative of the present invention refers to a saccharide having an amino group at the 2-position of glucoseamine, which is a constituent sugar of chitosan, and a reducing terminal, sodium cyanoborohydride (NaCNBH ₃ ) or an amine borane-based reducing agent such as Ammonia borane (NH ₃ BH ₃ ), monomethylamine borane “CH
₃ (NH ₂ BH ₃ ) ”or the like to form an amide bond between a saccharide having a carboxyl group terminal opened and / or a saccharide having a carboxyl group terminal released in a molecule. Things.

For the formation of this amide bond, the carboxyl group is reacted with SOCl ₂ at the terminal of the free carboxyl group of these saccharides, esterified with p-nitrophenol, or acid chlorided with phosphorus pentoxide or the like. It can be activated and reacted with the amino group at the 2-position of glucoseamine, which is a constituent sugar of chitosan, to obtain a chitosan derivative. Further, if necessary, a coupling agent may be used. Alternatively, a reducing agent may be used in combination with a system containing chitosan and a saccharide having a reducing terminal to release a carboxyl group and simultaneously form an amide bond.

As a method for activating a free carboxyl group of a saccharide having a reducing end, for example, D-galactopyranosyl-gluconic acid of a disaccharide can be used to activate the carboxyl group in the form of p-nitrophenyl ester. After activation and separation of the activating compound, it is reacted with the free amino groups of chitosan. This reaction is carried out in a solvent such as dimethylformamide (DMF), tetrahydrofuran (THF) or dimethylsulfoxide (DMSO) at room temperature or under cooling, and the reaction time is completed in several hours to several days.

Next, as the coupling agent, reactivity,
In consideration of selectivity, carbodiimide-based coupling agents such as N, N-dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (ECC), and the like can be used. ,
One or more of these coupling agents can be used in the reaction.

As the reducing agent, sodium cyanoborohydride (NaCNBH ₃ ) or an amine borane-based reducing agent such as ammonia borane (NH
₃ BH ₃ ), monomethylamine borane “CH ₃ NH ₂ BH ₃ ”, dimethylamine borane “(CH ₃ ) ₂ NHBH ₃ )”, trimethylamine borane “(CH ₃ ) ₃ NBH ₃ )”, pyridine borane (C ₅ H ₅ NBH ₃ )
And the like. One or two of these reducing agents can be used.
More than one species can be used in the reaction.

Further, hydroxyl groups and amino groups still released from the chitosan compound having a sugar side chain introduced thereinto were subjected to, for example, oxyethylene, oxypropylene addition, carboxymethylation, phosphorylation, sulphation, dihydropropylation and the like. Derivatives may be used.

The chitosan derivative obtained as described above is further purified by washing with a solvent and forming a precipitate, or by gel filtration, ion exchange column chromatography, activated carbon exchange column chromatography, cellulose dialysis membrane and the like. Can also.

The rate of derivatization of the saccharide having a reducing terminal with respect to chitosan of the present invention can be appropriately selected according to the purpose and application, but generally, it is preferably 10 to 100%.

The chitosan derivative of the present invention may be optionally adjusted by drying, concentration or dilution depending on the form and form of the melanin production promoter to be applied, and also the skin cosmetics and hair cosmetics.

The chitosan derivative of the present invention can be used as it is as a novel melanin-promoting agent as it is, and can be further incorporated into skin cosmetics and hair cosmetics, but the amount thereof is not particularly limited. It will vary slightly depending on the type or quality of the various applications and the degree of action expected.
Usually, 0.01 (w / v%) or more, preferably 0.05
(W / v%) is better. In addition, the compounding amount is 0.01 (w / v%)
If less, the effect cannot be expected sufficiently.

In addition, the melanin production promoter containing the chitosan derivative of the present invention, and further the skin cosmetics and the hair cosmetics, in addition to the above-mentioned essential components, if necessary, within a range not impairing the effects of the present invention. It can be manufactured by arbitrarily selecting and using components and additives used in pharmaceuticals, quasi-drugs, cosmetics, foods and beverages, and the like.

(1) Various fats and oils Avocado oil, almond oil, fennel oil, perilla oil,
Olive oil, orange oil, orange luffer oil, sesame oil,
Cocoa butter, chamomile oil, carrot oil, cucumber oil, tallow, tallow fatty acid, kukuinut oil, safflower oil, shea butter, 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, mocro, coconut oil, tallow, lard, or hydrogenated products of these oils (hardened oil, etc.).

(2) Waxes Beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax,
Montan wax, shellac wax, etc.

(3) Mineral oil Liquid paraffin, vaseline, paraffin, ozokeride, ceresin, microcrystalline wax, squalene, squalane, pristane, and the like.

(4) Fatty acids 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, isononanoic acid, caproic acid , 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2
-Synthetic fatty acids such as ethylhexanoic acid and isopentanoic acid.

(5) alcohols ethanol, isopropanol, lauryl alcohol,
Natural alcohols such as cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, and phytosterol; and synthetic alcohols such as 2-hexyldecanol, isostearyl alcohol, and 2-octyldodecanol.

(6) Polyhydric alcohols 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, glycerin, pentaerythritol, sorbitol, mannitol and the like.

(7) Esters Isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyl dodecyl myristate, hexyl decyl dimethyloctanoate, cetyl lactate, Myristyl lactate, diethyl phthalate, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, and the like.

(8) Metal soaps Aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, zinc undecylenate and the like.

(9) Gum, saccharides and water-soluble polymer compounds Arabic gum, benzoin gum, dammar gum, guaiac oil, 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, carboxymethyl chitin or hydroxyalkyl (C ₂ -C ₄ ) oxide to which alkylene (C ₂ -C ₄ ) oxide such as ethylene oxide is added _{2 to} C ₄ ) chitin or chitosan, low molecular weight 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, ethyl cellulose , Methylcellulose, carboxymethylcellulose, carboxyethylcellulose, sodium carboxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, nitrocellulose, crystalline cellulose, Vinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylic acid salts, polyalkylene oxide or crosslinked polymer thereof such as polyethylene oxide or polypropylene oxide, carboxyvinyl polymers, such as polyethyleneimine.

(10) Surfactant Anionic surfactant (alkyl carboxylate, alkyl sulfonate, alkyl sulfate, alkyl phosphate), cationic surfactant (alkyl amine 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 type amphoteric surfactant, nonionic surfactant (ether type nonionic) Surfactants, ether ester type nonionic surfactants, ester type nonionic surfactants, block polymer type nonionic surfactants, nitrogen-containing nonionic surfactants), other surfactants (natural surfactants) , Derivatives of protein hydrolysates,
Polymer surfactant, surfactant containing titanium and silicon,
Fluorocarbon surfactants).

(11) Various vitamins Vitamin A group: retinol, retinal (vitamin
A₁), Dehydroretinal (vitamin A_Two), Carochi
N, lycopene (provitamin A), vitamin B group: thia
Min hydrochloride, thiamine sulfate (vitamin B₁), Lvov
Rabin (vitamin B_Two ), Pyridoxine (vitamin
B₆), Cyanocobalamin (vitamin B₁₂), Folic acid,
Nicotinic acids, pantothenic acids, biotins, choline,
Inositols, vitamin C group: ascorbic acid and its
Derivatives, vitamin D group: Ergocalciferol (bi
Tamin D_Two), Cholecalciferol (vitamin D_Three),
Dihydrotaxerol, Vitamin E group: Tocophero
And its derivatives, ubiquinones, vitamin K group:
Tonadione (vitamin K₁), Menaquinone (vitamin
K_Two), Menadione (vitamin K_Three), Menadiol (bi
Tamin K_Four), Other essential fatty acids (vitamin F), mosquitoes
Lunitine, ferulic acid, γ-oryzanol, orot
Acids, vitamin Ps (rutin, eriocitrin, hesperi
Gin), vitamin U, etc.

(12) Various amino acids Valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid , Hydroxylysine, arginine, ornithine, histidine, and the like, and their sulfates, phosphates, nitrates, citrates, and amino acid derivatives such as pyrrolidone carboxylic acid.

(13) Various additives derived from plant or animal raw materials These are processed in a usual manner according to the type and form of the product to be added (for example, grinding, milling, washing, hydrolysis, Fermentation, purification, squeezing, extraction, fractionation, filtration, drying, pulverization, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization, etc. You can choose to serve.

The solvent used for the extraction may be selected in consideration of the purpose and type of the product to be provided, or the processing to be performed later. However, usually, water and a water-soluble organic solvent (for example, ethanol) are used. ,Propylene glycol,
1, selected from 1,3-butylene glycol)
It is desirable to use a species or a mixture of two or more species. However, when the content of the organic solvent is not preferable depending on the application, only water may be used, or ethanol which is easily removed after the extraction may be used, and may be used alone or in an arbitrary mixed solution with water. Exploited extract may be used.

It should be noted that additives derived from plant or animal raw materials are
When applied to systemic or topical external preparations and cosmetics, including protection of skin and hair, moisturizing, improvement of feel and texture,
Gives flexibility, relieves irritation, relieves stress due to aroma, activates cells (prevents cell aging), suppresses inflammation, improves skin and hair quality, prevents and improves rough skin, hair growth, hair growth, hair loss prevention, gloss Application, cleaning effect, alleviation of fatigue, promotion of blood flow,
In addition to cosmetic effects such as a warm bath effect, effects such as flavoring, deodorizing, thickening, preserving, and buffering can be expected.

As a specific plant (crude) used as a raw material,
For example, almond (Hen peach), eye (Aiba), blue oak
(Seifu Fuji), Aotsuji Lafzi (Kibo), Acacia, Akasuri Fruit, Red Grape, Red Megawiwa (Red Bud), Akane
(Kanekane Akane), Ayajiou Jiou (Jihuang), Agi (Awei),
Akinire (Royu skin), Akebi (Kidori), Asa (John Asako), Maruba Asagao or Asagao (Toshiko), Ashitaba (Asuka),
Azuki (red azuki), acerola, ase yak (Asenyaku), anise, Abemaki fruit, avocado, ama, amacha (sweet tea),
Amachaworu, Amadokoro (Tamatake), Amigasa lily (Shellfish), Altea, Arnica, Aloe (Length), Aloe vera, Angelica, Anzu Honganzu (Anjin), Ansokkou (Azuka), Ikakozolina (Biliary head), Itadori
(Tiger cane root), strawberry, fig (fructose) or its leaves, strawberry (winter aoiko), ichiyakuso, ginkgo (ginko leaf, ginkgo),
Itohimehagi (Enshi), carob, rice seed or seed coat,
Inondo seeds, Ibuki-kusou-so, nettle, ylang-ylang, fennel (Fenka), ukiyagara (sanryou), gull-kasukagra fruit, Hime-uikyo, turmeric (Utsukin), Usubasaishin-keirinsaishin (spicy), Usveniaoi,
Pterodactyla mushroom, Nepenthes (summer hay), Udo or Shishudo (Qang, Independent, Tang Independent), Plum (Ume) or its pulp, Vladigashi, Uwaurushi, Unshuri mandarin (Chen skin), Estragon, Ezocogi (Ezo fivega), Enoki ,
Ebisugusa (Keiko), Elderberry fruit, Elemi, Enju (Gossip, Gossip rice), Ogi-kibana-ohgi (Koki),
Ouren (yellow), giant crow squirrel (karonin), giant skull (self-defense), psyllium (vegetative child, vegetative grass), toucan hazel (Haruko), obanokera okera (white jitsu), obayashishabushi fruit, o hawthorn hawthorn ), Barley (barley), oguruma (turning over), okra fruit, panax ginseng and tochibanningi (carrot), hypericum persicae, gogomebato perforated flowers, perforated periwinkle (brother cut grass), odorikosou (interrupted), onamimimi (small earlings) (Tianhe), Onyuri Sasayuri Hakatayuri (Yuri), Ononis, Halibut (Hihayu), Ominaeshi (Loose), Dutch strawberry, Dutch mustard (Cresson), Dutch jelly, Dutch honey, olive, oregano, orange fruit or Pericarp, lycaenium (ripe yellow), cacao seeds, oysters or their leaves (persimmon), Fujikagi), Cassia, paper mulberry fruit (Kozomi), Zedoary (莪朮), oak
(Kazuki, Kazaha), Cascarilla, Kanixa (Kinosato), Kanokosou (Kisakune), Birch or Weeping birch (White birch), Pumpkin, Kapokinoki seeds, Kahoku Sansho (shopper), Gama (Kaba yellow), Chamomile roma Chamomile, kamiyatsude (weeds), crow squirrel (flower meadow), crow squirrel (midsummer), oak wheat, guarana seeds, karaya, karin (gourd), kawayanagi, kawataketake, kawarayomogi (inchinko), kansui
(Sweet), liquorice (licorice), candelilla, cantou, canna, raspberry, kiwi fruit, kikarasuri (urorone), kikyo (bellflower, bellflower root), chrysanthemum (chrysanthemum flower), catalpa (azumi),
Rumex (Yotei), Pheasant (Kikomi), Kizuta, Kidachi Aloe, Kidachiha, Kinoki, Yellowfin (Huangbashi), Gymnema sylvestre, Cabbage, Cabbage immature, Cucumber,
Kiraja saponaria, Kiraya, kumquat fruit, betel, kinmizukiki (sensuru-kusa), guava fruit, guayule,
Quercus Infectoria (Gallery), Kukui Nuts, Kukui (Gugi, Gyugia, Gyugoli, Leaf Skin), Kusagi Kazura (Tenmen Fuyu), Kuzu (Kakuzu), Kusunoki, Gooseberry Fruit, Gardenia, Kunugi Saw), Kumazasa, Kumatsuzura (horse whipweed), Clara (Bittersweet), Cranberry fruit,
Chestnut or its astringent skin, Curculigo latifolia fruit, grapefruit fruit, buckthorn, Black stalk
(Rescue), cloves (cloves, cloves), kayga (crop, crocodile spikes), celosia (cow flowers, rooster), bay laurel (laurel), gentiana, gennoshoko (old crocodile), koushinbara (moon season flowers) , Kosui mint (Melissa), Kozo fruit, Kocha (tea), Kouhone (Raw bone), Kouhon (Straw and Kara straw), Koulyan, Koendro fruit, Koganebana (Yellow Gon), Cowberry (Koshibachi), Coconut fruit, Goshyu
(Goshuyu), goshoichigo (covered bonko), pepper (pepper), copaiba balsam, coffee beans, kobushi tamshiba magnolia (spicy), burdock (burdock, burdock), kobotdur, sesame (sesame), sesame crab (gensin) ), Wheat (wheat), rice, rice bran (red bran, white bran), rice oil, cola acuminata seed, cola vera seed, fenugreek fruit, colombo, conzulango, kelp, konjac, comfrey (finnari grass), saxima Button ヅ (weird sen), cherry leaves, flowers, fruits, bark
(Cherry bark), cherry, pomegranate, sasa, lily
Sazanka, Sajiomodaka (Sawahka), Sweet potato, Sugarcane, Sugar beet, Sanebu jujube (Acid jujube), Saffron (Bamboo safflower, West safflower), Pomelo fruit, Sabonsou, Salmonberry fruit, Sarashinashoma (Masame), Salvia (Sage), Sawagikyo (Yamakona), Hawthorn (Yamazako), Panax ginseng (Seven carrots), Sanshuyu (Yasugoyu), Sansho (Sansho), Sandscon (Yamazone), Shea (Kareite), Cyanoki fruit, Shiitake ( Shiitake mushrooms), Shion (Shien), Dikitaris, Shikunshi (Kimiko), Shiso, Aodiso, Chirimenjiso, Catamendiso (Shiso leaves, Shiso), Rosewood, Shinano,
Chinese Forsythia (Forsythia), Zinnia (Chrysanthemum), Spiraea, Potato, Peony (Shakuyaku), Shajin (Shasan), Janohige (Bakumonyu), Juzudama, Palm Fruit,
Ginger (ginger), ginger (iris, iris root), shizuku fruit, birch oak seeds, white walnut butterflies, white blossoms, white blossoms, white blossoms, white blossoms, white cinnamon syllabus, cinnamon, watermelon, watermelon (Gold and silver flowers, Shinobi winter), sorrel (acid model), swimberry fruit, strawberry fruit, horsetail (Thorn), stevia, plum fruit, pine cone, cone larch,
Vines, walnuts, hawthorn,
Dandelion, horse chestnut (malonie), pear fruit, prunus japonicus, prunus japonicus, prunus edulis, prunus edulis, millefoil, balsam pears, pygmy root, pygmye pylon, ), Mallow, hirohasenega, senega, senega, seri, celery, senkyu
(River Kyu), Sendan, Senburi (Drug), Senna fruit or leaves, Senninsou (Large Tate), Soka (Grass), Buckwheat seeds,
Somenimo, Daio (daioh), Radish, Soybean, Daidai
(Orange, kikomi), takatodai (daigeki), takarababi (guin), dark sweet cherry fruit, hollyhock, hollyhock thyme (thyme, momoka), hollyhock (tachibana skin), hollyhock willow, tamarind seeds, onion, tamshiba ),
Tara tree or its root bark, tanjin (dansin), dandelion (gakko) or white dandelion and moko dandelion, dammar, cherry fruit, tigaya or its root (chinese), chikutsujin carrot (bamboo ginseng), chicory, ginseng (gomiko) , Korean ginseng (Rhuanghuang), Korean ginseng (Wuyi), Korean ginseng (Ginseng), Korean ginseng (Aiba leaf), Chinese ginseng (Irei), Japanese radish, Camellia,
Butterflies, clovers (lacquer primroses), twigs (ducklings), vines (red azuki), vines (red bean), vines, vines (vegetables), vines (four-leaf ginseng), vines, deco, teuchigurumi, duberry fruit, tengusa, tendaiyaku
(Crowd medicine), Pepper (winter melon), Pepper (bansho), Touki
(Return), calendula (marigold), corn or corn hair (southern hair), horned rattle (female Sadako), linden (dragonfly), dokudami (jujutsu), konkon (gem), tochibanjin (bamboo ginseng) ), Eucommia (Tonaka, Tonaka leaf), Tomato, Traganth, Triacanthus seed, Tormentilla, Dronoki, Troroaoi, Niseria berry fruit, Nagaimo yam (Yakuyaku), Nagiikada (Butcher bloom), Naginata kouji, Nazuna, Rapeseed, Natsumikan , Jujube (large jujube), naniwaiba (gold cherry), narco lily (yellow), peanut (peanut), nanten (minamiminami), nigaki (maki), sagebrush (bite), nikuzuku, nikkei (cinnamon), leek ( Nirako), elderberry (bone-bonded tree)
Fruit, flower or foliage, garlic (garlic), nurde (five times), leeks, thistle (daiji), wild rose (fruit), sawwood, nodake (maego), nobara, peach, palm, pineapple fruit, hibiscus (Bussouge) , Furinbussouge, roselle), hakata lily (lily), hakamauraboshi (bone crushing supplement), haxen (ringworm skin), huckleberry fruit,
Chickweed (Horiko), Hazel (Haruko), Hashidokoro (Roth Root), Basil, Lotus (Russian meat, Renko), Parsley (Netherland jelly), Hadamugi, Batata, Hachiku Madake (bamboo boiling), Patchouli, Mint ( Light-loading leaves), Adlay (Yokuinin), Hanasuge (Chimbo), Banana, Hanamint, Vanillabins, Papaya, Dipterocarpus (mouse koji), Hub grass, Paprika, Hamago and Mitsuba Hamago (Thorn troglodytes), Hamasuge (Katsukishi) , Hamabishi (Shikoriko), Hamanas (Maikai flower),
Hamabofu (beach storm), Hamamelis, Rose (rose), Parietaria, Harunire (Yellow, Yuhakuh, Yuba), Breadfruit,
Hiogi (sun dried), lizard carrot (party), pecan nuts, gangamana (stone and vines), cypress (extended life grass), cypress (hishomi), pistachio, beet, hitotsuba (stone reed), hinotakokochi ( Beef knee), hinoki, hiba, castor, sunflower, bell pepper, hemima, incense, himematsutake, pimenta fruit, juniper, hiyu fruit, belowo oyster, hirohaokinagusa (bakuohoku), loquat (loquat, loquat leaf),
Betel nut (large clothing skin, betel nut), sugar beetle (southern rattan), butterflies, coltsfoot (winter flowers, winter leaves), fujibakama (orchid grass), wisteria bean (tomato), grape fruit or pericarp / leaf, beech, fumulus mushroom (Cordyceps), Brazilian liquorice, black currant fruit, blackberry, plum fruit, flucellaria, blueberry (Acacia catechu), prunes, blond psyllium, bundou (mung bean), luffa, safflower (safflower), belladonna, berry fruit, boysen Berry fruit, boufu (windbreak), spinach, physalis (Torone), honoki (kopoku, sumkopaku), bokeh
(Gourd melon), Hosobananaokera (blue ajutsu), Hosobabarengiku, Bodaiju (bodaiju), button (peony, peony bark), hop, jojoba, whiteberry fruit, honshimeji, meizurutennanshaw (Tennan star), ephedra (mao), macadamia nut , Makuri (sea grass), Magwa (mulberry bark, mulberry leaf), mushroom
(Bamboo-boiled), matabi (mokuten tate), matsukasa, matsuba, matsuhodo
(Bukuryo), mayola (Hanaminka), malvanozadine (bitter), mulberry fruit, quince, malonie, mango, mangosteen, manshugulumi, mandarin fruit, mannentake (reishi), citrus fruit (kikomi), and mishimasaiko (saiko) ), Mizokokushi (half lotus), misohagi (senkakuna), mitsugashiwa, honeywort, honeysuckle maggot (vines), midorihakka, mimosa, mioga, miracle fruit fruit, myrrh, mirobaran, mukuge, mukunoki, mukuroji , Murasaki (purple root), Murasaki corn, Japanese swordfish (Essentiale grass), Mebogi, Melaleuca, Melissa, Meliloth, Melon fruit, Japanese mugwort, Moso bamboo, Mokkou (wood incense), Japanese maple, Peach leaf
(Peach leaves), fruits, seeds (peach kernels), bean sprouts, morello cherry fruits, moroheiya (burlap), yakawamurasakiimo, yakuchi
(Masutoshi), cornflower (cornflower), cornflower mint, yashabushi (arrow wheel), yachiyanagi, yatsude (octagonal lantern), mistletoe (yanagi parasite), willow leaf, yabugarashi, yabukouji (purple gold cow), yamagobo (land) ), Mountain alder (Yamaharu), bayberry (Yumebai), yamamogi, eucalyptus, yukinoshita (tiger ear grass), yucca flebifolia, yuzu fruit, lily, yorigusa, mugwort (autumn leaf), lime fruit, rye, lacanca fruit, raspberry Leaf / fruit, lavender, longan (longan meat), ryocha (green tea), apple fruit, gentian, lubas suavisimus (sweeten), lettuce, red currant fruit, lemon fruit, lemongrass, forsythia, astragalus, wax palm , Loganberry fruit, Logwood, Rosemary (Mannenrow), Rosehip (Nobara), Wakame, Wa Bi, and the like burnet (Chinire).

Examples of the seaweeds include seaweeds [green algae: Chlorella vulgaris, Chlorella pyrenoidosa, Chlorella ellipsoidia, Usbaaonori, Suziahonori, Hiraaonori, Bouuaonori, Hosoedaoonori], and seaweeds [Brown algae: Macombum, Lyconib, Hosoibu] Honey kelp, wakame, hirome, blue seaweed, macrocystis pilifera, macrocystis integrifolia, neocitys luetokeana, hijiki, hibamata], seaweed [red algae: red alga: jijirimen, maxa (tengusa), hirakusa, onyxa, obaxa, kataobaxa ,
Yatabegusa, Yuikiri, Shimatengusa, Tosakanori, Togekirinsai, Akumasakirinsai, Kirinsai, Byaksinkirinsai, Tsunomata, Obatsunomata, Tochaka (Yahatsunomatata), Ezotunomata, Togetsunomata, Hirakotonogi, Kotoji, Kotoji , Heius Banori] and the like.

Other algae, for example, green algae (Chlamydomonas: Chlamydomonas, Akayukimo, Dunaliella: Dunaliella, Chlorococcus: Chlorococcus, Kwanomimo: Kwanomimo, Volvox: Ohigewari, Volvox, Palmera, Yotsumemo, Spirogyra: Hizaori, Spirogyra, Tulsimidro, Hibimidro: Hibimidoro, Aosa: Anaoasa, Amiosa, Nagaosa, Kawanori: Kawanori,
Genus Fricciella, genus genus: medusa, asamidori ogusa, kawashiogusa, marimo, valonia: tamagobaronia, tamabaronia, magnum: tamatamamo, iwata: husaiwata, suricogita, heraiwirata, crocodile, crocus Sakibutimimil, Nagamil, Hiramil, and Casanori:
Casa nori, Juzumo
Species of the genus Mizudzumo, Genus genus, Colecaetus, Genus genus genus, Species of the genus Rosa: Rosa spp. Genus (Suizenjinori: Suizeninori, Aokko, Nostoc: Kawatake, Ishikurage, Hassai, Yuremo, Racenmo (Spirulina): Spirulina,
Genus trichodesmium (Aiakashio)), brown algae (Piraella spp .: Pyraella spp., Shiomidoro spp .: Nagamioshidoro, Isogrape spp .: Isogrape, Isogawara spp .: Isogawara, Krogashira spp .: Gunsenkurogashira, Kasilaki spp .: Kashirazaki, Muchimo spp .: Muchimo, Hiramchimo, Kebelligsa, Amidixa: Amidixa, Sakibiroamiji,
Sanadagusa: Sanadagusa, Fukurinamiji, Commongusa: Commongusa, Yahuzugusa: Ezoyahazu, Yahuzugusa, Uraboshiyahazu, Jingamigusa: Jigamigusa, Umiuchiwa: Genus Umiuchiwa, Konamiumichusawa, Akabaumikawasuna Genus Nabarimo, Chasoumen spp. , Mozuku: Mozuku, Ishige: Ishige, Irolo, Icmegasa: Ichimegasa, Carapacea: Callidia, Umibos: Umibos, Urushigusa: Urushi Sa, Keurushigusa, Tabakogusa, Konbumodoki genera: Konbumodoki, Habamodoki genera:
Genus Habanomoki, Genus Habanori: Havanori, Genus Habanori: Habanori, Common Bukuro: Common Bukuro, Ezobukuro: Ezobukuro, Fukuronori: Fukuronori, Watamo, Chishimafukuronori Genus: Genus Genus, Kagomenorimura, Genus Kamuramemura ： Genus Shark, Genus Genus: Genus Genus, Genus Genus: Genus Genus, Genus Genus: Genus Lily, Genus Genus: Genus Genus, Genus Genus:
Turmo, Anatome: Aname, Siberium: Sujime, Misujikombu: Misjikombu, Atsubamisujikombu, Kombu: Gatsugarakomubu, Oysterfish, Onicombu, Goheikombu, Nagakombu, Pea, Ootomikombu, Torokomokuto: Torokontokuto , Genus genus: swordfish, swordfish, black squid, genus scorpionum: squirrel, squirrel genus: squirrelcomb, kuroshiome: kuroshiome, scorpion genus: feline sacion, alame genus: alame, Ainuokame: Ainuwakame, squid, squid Ezoishige, Yabamoku: Yabamoku, Rappermoku: Rappermoku, Jiromoku: Uganomok,
Joromok, Hyemok, Hondawara: Tamanashimoku,
Isomok, Nagashimamoku, Akamoku, Shidamoku, Hondawara, Nejimoku, Narasamo, Mametara, Tatsukuri, Yasumatamoku, Umitranoo, Oobamoku, Fushizushimoku, Hahakimoku, Togemoku, Jolemoku, Sawtooth moku,
Obanokogirimoku, Sugimoku: Sugimoku, Ukimo: Oukimo, Buruquimo: Burukimo, Kayamonoli: Kayamonori, etc., Red algae (Ushikenori: Ushikenori, Funorinoushike, Amanori: Asakusanori,
Susabinori, Uppluinori, Onimanori, Tasa, Filitasa, Benitasa, Rhodocorton spp. Pine genus:
Pine L., Fusanori: Fusanori, Nisefusanori: Nisefusanori, Sodegarami: Sodegarami, rattle:
Rattle rattle, rattle rattle, broad-spotted genus: broad-spotted scorpion, scorpion genus: small-spotted squirrel, genus Kagikenori: Kaginori, Kakenenori, Tengusa genus: Himetengusa, Hytengusa, Oobusa, Nambugusa, Kohido, Kohira, Kojira, Ohihime, Kohido, Kouhira, Ohihime ： Genus genus: genus genus: genus genus: genus ryegrass, genus ryumunsou, genus rhyme, genus rhinoceros, genus nisekarekigusa genus: genus foxes, genus okitsubara: genus syllabus, genus akaba: genus akaba, malvagana, sagogana : Genus Shiogosagoromo, Genus Iwanoka: Genus Etsukiiwanokawa, Genus Kinokawa: Genus Kinokawa, Genus Kaninote: Genus Kaninote, Coral: Coral genus, Mucadenori: Mucadenori, Suzukade, Catanori, Hiramukade, Kyounohimo, Sakuranori, Nikumukade, Tambanori, Crane, Isonohana: Nuraksa, Cronulaxa, Omodenori, Hirakintoki: Hirakintoki
Genus: scorpionfish, genus: serrata,
Kintoki, Matsunori, Komenori, Tosukamatsu, Atsumatsu, Kakurite spp. Genus: genus genus: genus genus: quinuhada; Species of Susqueke Beni: Species of Suska Kebeni, Species of Okamuragusa: Yamadagusa, genus of Mirin: Mirin,
Hosobamilin, Tosakanori: Kikutosaka, Ezonameshi: Ezonameshi, Isomokka: Isomokka, Yukari: Yukari, Hosoyukari, Ibaranori: Ibaranori,
Rhinoceros rose, Tachiibara, Kagibaranori, Kijinoo genus: Chidinooo, Isodanthus: Isodanthu, Atsubanori genus: Atsubanori, Ogonori: Ogonori, Tsurushiramo, Silamo, Ogonori, Mizokonori, Kabanori,
Genus genus: beetle scrophulari, fushikrenori genus: fushikrenori, namitake mushroom: namiitake mushroom, sponge genus: sponge beetle, okinori genus: okitsunori, saimi genus: itanigusa, simi, harugane,
Lotus spp .: Lotus spp.
Hosoibonori, Nobonori, Scrophulariaceae: Kurohaginnansou, Akabaginansou: Akabaginnansou, Hishibukuro: Hishibukuro, Madaragusa: Togemadara, Ekimadara, Taoyanagisou: Hanagusa ： Hanaedae, Hirata goats ：
Hirata goat, genus Darus: dars, masagoshibari, anadarus, eubagusa genus: eubagusa, Benifukuronori genus: Benifukukuronori, fushitsunagi: fushitsunagi, himefushinushigi, hirohafushinagi, kawanatsugisugisai, genus tsutsugigigi , Honey Negis, Amixa, Egonori: Egonori, Futigis, Saeda: Saeda,
Chrysanthemum spp .: Chrysanthemum spp. Genus: Aristolochia, Ayanishi, Genus: Ayanishi,
Genus Ayaginu: Genus Ayaginu, Genus Dadia: Enashidazia, Genus Shimadada: Isohagi, Shimadadia, Genus Dazimodoki: Dazimomodoki, Itogusa: Moletogusa, Futigusa, Macri Genus: Makri, Sanaginori: Hanayanagi, Yuna, Yanaginori, Motsunagi
Sasabayanaginori, genus Sozo: Closozo, Kobusoso, Hanesozo, Sozonohana, Hanegusa: Hanegusa, Kehanegusa, Kozanemo genus: Kozanemo, Isomurasaki, Hosokozanemo, Himegoke genus: Himegoke, Kurohimegoshi, Hioudoogushigu , Genus genus: genus cypress, genus genus: genus isola, genus genus: genus genus: genus genus, genus syllabus: genus sylvestris, genus sculpture: genus sculpture: genus genus, genus genus, and : Chinolimo, Chisinori: Chisinori, etc., and axle algae (Shajikumo, Shiratamamo, Hossiturimo: Hossiturimo, Lichnotatum, Fussurimo) Rascomo genus: Himejimo, Chabo hiramo, Tripera, etc.), Yellow algae (Hikarimo genus: Hikarimo etc.) and the like.

[0045] Materials derived from animal raw materials include a cockscomb extract, a cow / human placenta extract, a pig / cattle stomach, a duodenum or an intestinal extract or a decomposition product thereof, and a pig / cattle spleen extract. Products or their degradation products, extracts of swine or bovine brain tissue, water-soluble collagen, collagen derivatives such as acylated collagen, collagen hydrolysates, elastin, elastin hydrolysates, water-soluble elastin derivatives, keratin and its decomposition products Or a derivative thereof, a silk protein and its degradation product or a derivative thereof, a pig / bovine blood cell protein degradation product (globin peptide), a pig / bovine hemoglobin degradation product (hemin, hematin, heme, protohem, heme iron, etc.), milk , Casein and its decomposition products or their derivatives, skim milk powder and its decomposition products or their derivatives, lactoferrin or its decomposition products, chicken egg ingredients Such as fish meat decomposition products.

(14) Microbial culture metabolite Yeast metabolite, yeast extract, rice ferment extract, rice bran extract, euglena extract, lactic acid fermentation product of skim milk powder, trehalose or a derivative thereof.

(15) α-hydroxy acid Glycolic acid, citric acid, malic acid, tartaric acid, lactic acid and the like.

(16) Inorganic pigments Silicic anhydride, magnesium silicate, talc, kaolin,
Bentonite, mica, titanium mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide,
Titanium oxide, calcium carbonate, magnesium carbonate, yellow iron oxide, red iron oxide, black iron oxide, gunjou, chromium oxide,
Chromium hydroxide, carbon black, calamine, etc.

(17) UV absorber / blocker p-aminobenzoic acid derivative, salicylic acid derivative, anthranilic acid derivative, coumarin derivative, amino acid compound,
Benzotriazole derivatives, tetrazole derivatives, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives, camphor derivatives, furan derivatives, pyrone derivatives,
Nucleic acid derivatives, allantoin derivatives, nicotinic acid derivatives,
Vitamin B ₆ derivatives, benzophenones, oxybenzone, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine, neoheliopan, urocanic acid derivatives, escalol, zinc oxide, talc, kaolin and the like.

(18) Oxidizing agent Hydrogen peroxide solution, sodium persulfate, ammonium persulfate, sodium perborate, urea peroxide, sodium percarbonate, sodium tripolyphosphate, sodium bromate, potassium bromate, pyrroline peroxide Sodium acid, sodium orthophosphate, sodium silicate hydrogen peroxide adduct, sodium sulfate sodium chloride hydrogen peroxide adduct, β-tyrosinase enzyme solution, mushroom extract and the like.

(19) Dye agent 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, meta-hydrochloride Phenylenediamine, orthoaminophenol, N-phenylparaphenylenediamine acetate, 1,4-diaminoanthraquinone, 2,6-diaminopyridine, 1,5-dihydroxynaphthalene, toluene-2,5-diamine, toluene-3,4-diamine, Nitroparaphenylenediamine, paraaminophenol, paranitroorthophenylenediamine, paraphenylenediamine, paramethylaminophenol, picramic acid, sodium piclamate,
N, 'N-bis (4-aminophenyl) -2,5-diamino-1, -4-quinonediimine, 5- (2-hydroxyethylamino) -1-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 sulfate
5-diamine, nitroparaphenylenediamine sulfate, paraaminophenol sulfate, paranitroorthophenylenediamine sulfate, paranitrometaphenylenediamine sulfate, paraphenylenediamine sulfate, paramethylaminophenol sulfate, metaaminophenol sulfate, metaphenylenediamine sulfate, catechol , Diphenylamine, α
-Naphthol, hydroquinone, pyrogallol, phloroglucin, gallic acid, resorcin, tannic acid, sodium 2-hydroxy-5-nitro-2 ', 4'-diaminoazobenzozen-5'-sulfonate, hematein and the like.

(20) Acceleration of turnover / cell activation Hydroquinone, lactic acid bacteria extract, placenta extract, reishi extract, vitamin A, vitamin E, allantoin, spleen extract, thymus extract, yeast extract, fermented milk extract, plant extract ( Aloe, ogon, horsetail, gentian, burdock,
Sicon, carrot, hamamelis, hop, yokunin,
Odikoso, Assemble, Touki, Toukensenka, Amacha, Hypericum, Cucumber, Periwinkle,
Rosemary, parsley, etc.)

(21) Astringent succinic acid, allantoin, zinc chloride, zinc sulfate, zinc oxide, calamine, zinc p-phenolsulfonate, potassium aluminum sulfate, resorcinol, ferric chloride, tannic acid (including catechin compound) Such.

(22) Active oxygen scavenger SOD, catalase, glutathione peroxidase and the like.

(23) Antioxidants ascorbic acid and its salts, stearic acid esters, tocopherol and its ester derivatives, nordihydroguaseletenic acid, butylhydroxytoluene (BHT),
Butylhydroxyanisole (BHA), hydroxytyrosol, parahydroxyanisole, propyl gallate, sesamol, sesamolin, gossypol and the like.

(24) Lipid peroxide production inhibitor β-carotene, plant extract (cultured sesame cells, amateur,
Hypericum, Hamamelis, Clove, Melissa, Emmeiso, Birch, Sage, Rosemary, Minami Minami,
Kina, age, ginkgo, green tea, etc.)

(25) Anti-inflammatory agent Ictamole, 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 salts, glycyrrhetinic acid and its salts and the like.

(26) Disinfectant / Disinfectant Acrinol, sulfur, benzalkonium chloride, benzethonium chloride, methylrosaniline chloride, cresol, calcium gluconate, chlorhexidine gluconate, sulfamine, mercurochrome, lactoferrin or a hydrolyzate thereof.

(27) Moisturizer Glycerin, propylene glycol, 1,3-butylene glycol, hyaluronic acid and its salts, polyethylene glycol, chondroitin sulfate and its salts, water-soluble chitin or chitosan derivatives, sodium lactate and the like.

(28) Agent for hair Selenium disulfide, alkylisoquinolinium bromide solution, zinc pyrithione, biphenamine, thianthol, castal tincture, show tincture, capsicum tincture, quinine hydrochloride, strong aqueous ammonia, potassium bromate, bromate Sodium, thioglycolic acid, etc.

(29) Flavors Natural animal flavors 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, perilla essential oil, cedarwood essential oil, citronella essential oil, jasmine essential oil, ginger grass essential oil, cedar essential oil, spearmint essential oil, western Mentha essential oil, Great Fengxiang essential oil, Tuberose essential oil, T-shaped essential oil, Orange flower essential oil, Winter green essential oil, Truval sam essential oil, Batturi essential oil, Rose essential oil, Palmarosa essential oil, Cypress essential oil, Hiba essential oil,
Sandalwood essential oil, Petitgren essential oil, Bay essential oil, Vetiva essential oil, Bergamot essential oil, Peruvian balsam essential oil, Boad rose essential oil, Camphor essential oil, Mandarin essential oil, Eucalyptus essential oil, Lime essential oil, Lavender essential oil, Linaloe essential oil, Lemongrass essential oil, Lemon essential oil, Rosemary Vegetable flavors such as essential oils and Japanese peppermint essential oils, and other synthetic flavors.

(30) Dyes / colorants Red cabbage dye, red rice dye, madder dye, anato dye, squid dye, turmeric dye, ende dye, krill dye, persimmon dye, caramel, gold, silver, gardenia dye, corn dye , Onion pigment, tamarind pigment, spirulina pigment, buckwheat whole plant pigment, cherry pigment, laver pigment, hibiscus pigment, grape juice pigment, marigold pigment, purple potato pigment, purple yam pigment, lac pigment, rutin, etc.

In addition, humectants, hormones, sequestering agents, pH adjusters, chelating agents, preservatives / anti-binders, fresheners, stabilizers, emulsifiers, animal and plant proteins and their decomposition products, animal and plant Vegetable polysaccharides and their degradation products, animal and vegetable glycoproteins and their degradation products, blood flow enhancers, anti-inflammatory and anti-allergic agents, cell activators, keratolytic agents, wound healing agents, foam enhancers, thickeners Agents, oral agents, deodorants / deodorants, bitters, seasonings, enzymes, and the like can be used, and when used in combination therewith, various additive and synergistic effects can be expected.

The melanin production promoter containing the chitosan derivative of the present invention, and further the skin cosmetic and the hair cosmetic may be in any dosage form, such as capsule, powder, granule, solid, liquid, Gels, foams, emulsions, creams, ointments, sheets and other pharmaceuticals, quasi-drugs, skin
It can be blended and used in cosmetics for hair and bath agents.

Specifically, for example, basic preparations such as external preparations, lotions, emulsions, creams, ointments, lotions, oils, and packs, facial cleansers and skin cleansers, shampoos, rinses, hair treatments, and hairdressings , Perm agents, hair tonics, hair dyes, hair growth and hair restoration, etc., makeup cosmetics such as foundation, lipstick, blusher, eyeshadow, eyeliner, mascara, perfumes, bath agents, and other toothpastes , Mouth freshener ・
Gargle, deodorant / deodorant, sanitary cotton, wet tissue,
Alternatively, the present invention can be applied to various products such as an agent for preventing bleaching of hair, fur, wool and other types of animal hair.

The method for adding the melanin production promoter of the present invention to the skin cosmetics and the hair cosmetics may be added in advance or during the production.
What is necessary is just to select suitably in consideration of workability.

[0067]

EXAMPLES The present invention will now be described with reference to production examples, test examples, and prescription examples, but the present invention is not limited to these examples.

(Production Example 1) 5.0 g of D-galactopyranosyl-gluconic acid was dissolved in 30 ml of TEMED buffer (50 mM tetramethylenediamine, PH4.7), and 5.0 g of carbodiimide hydrochloride (EDC) was added thereto. Stir for a minute. Next, 10 g of a chitosan (manufactured by Yaizu Suisan Kagaku Kogyo KK, 33% deacetylation degree) was dissolved in 10 g of TEMED buffer solution 12 in this EDC solution.
Add 0 ml and stir for 3 days. During this time, 3.3 g of EDC is added in several portions. Thereafter, low molecular components were removed by dialysis, washed and dried to obtain about 12.5 g of a chitosan derivative of the present invention (chitosan-lactose derivative: about 31.5% of lactose induction, confirmed by ¹³ C-NMR).

(Production Example 2) 150 ml of water was added to 10 g of chitosan (manufactured by Yaizu Suisan Chemical Co., Ltd., degree of deacetylation: 85%), stirred and dispersed, and the pH was adjusted to 11 with an aqueous sodium hydroxide solution.
After adjusting to, the mixture is heated to 70 ° C. Next, 5.25 ml of hydrogen peroxide (about 35% concentration) was added and reacted for 3 hours. After the reaction was completed, the reaction solution was removed, washed with water and dried to obtain low molecular weight chitosan (deacetylation degree 89%). About 8.0 g was obtained. Next, 1.0 g of this low-molecular-weight chitosan is placed in a 300 ml flask, and 50 ml of a mixed solution of methanol / 1% acetic acid aqueous solution = 1/1 is added and dissolved. 5.0 g of maltose is added and dissolved, and then cyanoborohydride is further added. 2.5 g of sodium was added and reacted for 5 hours. After completion of the reaction, the mixture was washed with 300 ml of a mixed solution of acetone / water = 5/1 and 300 ml of ether and dried, and the chitosan derivative of the present invention (chitosan-maltose derivative: maltose induction ratio about 42.5%) was reduced to about 1.7%.
g obtained.

(Test 1) Test for promoting tyrosinase activity "Test method" 1.0 ml of tyrosine solution (L-tyrosine: 0.3 mg / ml), 1.0 ml of McClubine buffer (pH 6.5) and sample (chitosan derivative: Production Example) 1) Mix 0.9 ml of the solution, leave it in a thermostat at 37 ° C. for about 10 minutes, add 0.1 ml of tyrosinase solution (mushroom-derived, 2500 units / ml), and measure the absorbance at 475 nm. After measurement (A), the reaction solution is left in a thermostat at 37 ° C. for 10 minutes, and then the absorbance at 475 nm is measured similarly (A ′). At the same time, as a blank, a solvent (purified water) was added instead of the sample, and the absorbance was measured (a) and (a ') by the same operation, and the tyrosinase II activity promotion rate was determined by Equation 2, and the results were shown in FIG. 1 is shown. The same concentrations of kojic acid and arbutin were used as controls.

[0071]

(Equation 2)

[0072]

FIG.

[Test Results] As shown in FIG. 1, it was confirmed that the chitosan derivative of the present invention had a tyrosinase activity promoting action. Similarly, the chitosan derivative of the present invention (Preparation Example 2) was confirmed to have almost the same terosinase activity promoting action as in Preparation Example 1.

(Test 2) Melanin production promoting action test The present inventor decided to test and evaluate the melanin production promoting action based on B16 melanoma cells.

[Test Method] B16 melanoma cells pre-cultured for 24 hours are transferred to a fresh medium, and a sample is added to the medium at 2% and cultured for 2 days. Next, the cultured cells are treated with trypsin and dissolved by heating with 1N-NaOH, 10% DMSO solution.
Measure the absorbance at nm. In addition, instead of the sample, distilled water was used as a blank, and cells to which the sample was added at the same time were subjected to the MTT reduction method (Tim Mosmann; Journal of Immunology).
The activity was measured by logical methods p55-63 (1983)), and the MTT reduction activity of the sample-loaded cells was calculated using the MTT reduction activity of blank cells as one unit. The amount of melanin in the sample was calculated as absorbance / MTT reducing activity (1 unit), and the promoting effect on the amount of melanin produced by blank cells was determined. The results are shown in FIG.

[0076]

FIG. 2

[Test Results] As shown in FIG. 2, it was confirmed that the chitosan derivative of the present invention had a melanin production promoting action. Similarly, with the chitosan derivative of the present invention (Production Example 2), almost the same melanin generation promoting action as that of Production Example 1 was confirmed.

(Test 3) Safety Test (1) Primary Irritation Test for Skin Purified water of the chitosan derivative of the present invention obtained in Production Examples 1 and 2 so that the dry solid concentration becomes about 0.5 ^W / _V %. And applied to the skin of Japanese white rabbits (female, 3 per group, weighing about 2.3 kg) whose back was shaved. Judgment is 24,4 after application
Erythema and edema were performed at 8,72 hours by primary irritation scoring. The result was negative in all animals without any erythema and edema.

(Test 4) Safety test (2) Acute toxicity test Similarly, the chitosan derivative of the present invention obtained in Production Examples 1 and 2 was purified water so that the dry solid content concentration was about 10 ^W / _V %. Orally administered to ddy mice (male and female, 5 mice / group, 5 weeks old) in a dose of 2,000 mg / kg prepared for 4 hours before the test. Observed. As a result, no abnormalities were observed in all the mice for 14 days, and no abnormalities were observed in the dissection results. Therefore, LD ₅₀
It was determined to be 2,000 mg / kg or more.

(Prescription examples) Production of melanin production promoter, skin cosmetic and hair cosmetic In accordance with the above evaluation results, the following formulation examples are shown. It may be manufactured, and only the compounding amount is shown. Further, the present invention is not limited to these.

(Formulation Example 1) Emulsion weight% 1. Isopropyl myristate 2.0 2. Stearic acid 2.0 3. Oleyl oleate 6.0 4. Vaseline 2.0 5. Stearyl alcohol 1.0 6. Glycerin monostearate 2.0 7. Production Example 1-3 % Chitosan derivative aqueous solution 3.0 8.1,3-butylene glycol 10.0 9. Triethanolamine 1.0 10. Carboxyvinyl polymer 0.1 11. Preservative qs 12. flavor qs 13. Purified water 100

(Formulation Example 2) Lotion% by weight 1.1,3-butylene glycol 15.0 Polyethylene glycol 400 10.0 3. Ethanol 10.0 4. Polyoxyethylene (60) hydrogenated castor oil 2.0 5. 3% aqueous solution of chitosan derivative of Preparation Example 2.0 6. Appropriate amount of pH adjuster 7. Appropriate amount of flavoring agent 8. Purified water 100

(Formulation Example 3) Peel-off pack weight% 1. Glycerin 5.0 2. Propylene glycol 4.0 3. Polyvinyl alcohol 15.0 4. Ethanol 8.0 5. Polyoxyethylene glycol 1.0 6. 2% chitosan derivative aqueous solution of Production Example 1 3.0 7 Appropriate amount of fragrance 8.Purified water 100 residue

(Formulation Example 4) Cold cream weight% 1. Salicone beeswax 11.0 2. Liquid paraffin 22.0 3. Lanolin 10.0 4. Almond oil 15.0 5. Borax 0.5 6. 2% chitosan derivative aqueous solution of Production Example 2 2.0 7. Appropriate amount of fragrance 8. Residue to 100 purified water

(Formulation Example 5) Shampoo wt% 1. Triethanolamine lauryl sulfate 5.0 2. Sodium polyoxyethylene lauryl ether sulfate 12.0 3.1,3-butylene glycol 4.0 4. Diethanolamide laurate 2.0 5. Disodium edetate 0.1 6. 3% chitosan derivative 30% ethanol aqueous solution of Production Example 1 4.0 7. Appropriate amount of perfume

(Formulation Example 6) Body soap weight% 1. Potassium laurate 15.0 2. Potassium myristate 5.0 3. Propylene glycol 5.0 4. 2% aqueous solution of chitosan derivative of Production Example 4.0 4. Appropriate amount of pH adjuster 6. Perfume Appropriate amount 7.Residual water to be 100

(Formulation Example 7) Rinse weight% 1. Stearyltrimethylammonium chloride 2.0 2. Cetostearyl alcohol 2.0 3. Polyoxyethylene lanolin ether 3.0 4. Propylene glycol 5.0 5. 2% chitosan derivative aqueous solution of Production Example 1 2.0 6 .2% chitosan derivative aqueous solution of Production Example 2.0

(Formulation Example 8) Hair liquid weight% 1. Ethanol 29.0 2. Polyoxypropylene butyl ether phosphoric acid 10.0 3. Polyoxypropylene monobutyl ether 5.0 4. Triethanolamine 1.0 5. 2% aqueous solution of chitosan derivative of Production Example 1 1.0 6. 2% chitosan derivative 50% ethanol aqueous solution of Production Example 2 2.0 7. Perfume appropriate amount

(Formulation Example 9) Hair tonic weight% 1. Ethanol 40.0 2. Ethyl oleate 2.0 3. Polyoxyethylene (40) hydrogenated castor oil 2.0 4. 3% aqueous solution of chitosan derivative of Production Example 2.0 5. Perfume appropriate amount 6. Residue with 100 purified water

(Formulation Example 10) Granule bath agent weight% 1. Sodium bicarbonate 60.0 2. Anhydrous sodium sulfate 30.0 3. Borax 7.0 4. Chitosan derivative powder of Production Example 1 3.0

(Formulation Example 11) Coating protective agent A gauze or liniment cloth is impregnated with a formulation solution prepared by mixing an appropriate amount of the 3% chitosan derivative aqueous solution of Production Example 1, antibiotics, anti-inflammatory, etc., and attached to the wound. Alternatively, a 3% aqueous solution of chitosan derivative may be directly applied locally and covered with gauze or the like.

(Test 5) Use Effect Test The effect when the skin cosmetic of the present invention was actually used was examined. Use test is 20 ~ without skin disease
Apply the appropriate amount of the emulsion of Formulation Example 1 to the face and upper arm for 6 months, twice daily, before bathing and after getting up in the morning, with 10 male and female 50-year-olds as panelists. Was carried out by evaluating the color tone every two months. or,
Similarly, for 10 males aged 40 to 60 who do not have a head disease and have rather conspicuous gray hair, after washing their hair every day, apply an appropriate amount of the hair tonic of Formulation Example 9 to a certain part of the hair in 6 months. Subsequently, a use test was performed by evaluating the color tone every two months. As a control, an emulsion prepared by removing the chitosan derivative of the present invention from a hair tonic and using the same method was used. The evaluation method was visually performed according to the following criteria. The results are as shown in Tables 1 and 2, and the numerical values in the table represent the number of persons.

"Evaluation of Color Tone" Effective: The color tone of the coated part was higher in darkness than the surrounding area. Slightly effective: the color tone of the applied portion was slightly increased in darkness compared to the surroundings. Invalid: No change.

[0094]

[Table 1]

[0095]

[Table 2]

[Test Results] As shown in Tables 1 and 2, it was confirmed that the skin cosmetics and the hair cosmetics of the present invention blackened the color tone of the skin or hair.

[0097]

Industrial Applicability The chitosan derivative obtained by reacting the chitosan of the present invention with a saccharide having a reducing terminal has an effect of promoting melanin production and is safe for humans and animals. . Therefore, it can be applied to melanin production promoters, and further to skin cosmetics and hair cosmetics, and can darken skin or hair (hair, fur, feathers, etc.) without danger of ultraviolet irradiation. it can. Further, it has an effect of preventing graying of hair and can be applied to external preparations for skin in the field of pharmaceuticals / quasi-drugs or cosmetics (including various preparations used for humans and other animals). In addition, the present invention can be applied to various products such as an anti-bleaching agent for hair, fur, wool and other kinds of animal body hair.

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[Procedure amendment]

[Submission date] January 27, 1997

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Brief description of drawings

[Correction method] Added

[Correction contents]

[Brief description of the drawings]

FIG. 1 is a diagram showing the tyrosinase activity promoting action.

FIG. 2 is a diagram showing a melanin production promoting action.
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[Procedure amendment]

[Submission date] December 19, 1997

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0023

[Correction method] Change

[Correction contents]

The substitution rate of the amino group of the chitosan derivative of the present invention is used in the range of 0.1 to 100%. In order to obtain a higher antibacterial activity, the substitution rate of 0.5 to 50% is preferably used. Used.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 7/08 A61K 7/08 7/48 7/48 7/50 7/50 31/73 ADA 31/73 ADA

Claims (3)

[Claims] (1) A melanin production promoter comprising a chitosan derivative obtained by reacting chitosan with a saccharide having a reducing end. 2. A skin cosmetic comprising the melanin production promoter according to claim 1. 3. A hair cosmetic comprising the melanogenesis promoter according to claim 1.