JPH10158305A - Antimicrobial and antiseptic agent containing chitosan derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an antimicrobial and antiseptic agent that contains a chitosan derivative prepared by reaction of a chitosan with a saccharide bearing a reducing terminal group and shows the action to inhibit the proliferation of bacteria such as Escherichia coil of Staphylococcus aureus with an increased safety. SOLUTION: Chitin obtained from crabs or the like is treated with alkali and with an enzyme to effect deacetylation to prepare a chitosan of a deacetylation degree of >=50%. This chitosan is allowed to react with a saccharide bearing reducing terminal groups such as glucose in the presence of a coupling agent, for example, N,N-dicyclohexylcarbodiimide to prepare the objective chitosan derivative. This derivative as an antimicrobial and antiseptic agent is formulated to produce a skin preparation for external use, a bathing medicine, beverages and food products, and a fiber treatment agent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

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

[0002] The field of application is generally applicable to various internal and external preparations (including preparations used for animals), and specifically, ampules, capsules, pills, tablets, and powders. 1) Pharmaceuticals, 2) Quasi-drugs, 3) Foods, 4) Topical or systemic skin cosmetics, 5) Scalp / hair Pharmaceutical and / or cosmetic preparations (eg, shampoos, rinses, treatments, permanent solutions, hair dyes,
Hairdressing agents, hair tonics, hair growth / hair restoration, etc.), 6) bath agents used in bath water, 7) other deodorants / deodorants, sanitary goods, sanitary cotton, wet tissues, etc.

[0003] Further, as foods and drinks, oral compositions (gum, candy, etc.), processed seafood products such as kamaboko and chikuwa, livestock products such as sausage and ham, Western confectionery, Japanese confectionery, raw noodles, Chinese noodles, and yudenmen Noodles such as buckwheat, sauce, soy sauce, sauce, sugar, honey, powdered candy, mizuame, spices such as curry powder, mustard powder, pepper powder, jam, marmalade, chocolate spread, pickles, soy sauce, Processed vegetables and fruits such as sprinkles and canned and bottled vegetables and fruits, dairy products such as cheese, butter, yogurt, miso soup, soup, fruit juice, vegetable juice, whey drinks, soft drinks, alcoholic beverages, etc. Use in general foods and drinks such as health foods.

Examples of the fiber treatment agent include general clothing (pajamas, shirts, pants, socks, bras, panties, tights, slips, blouses, pants, skirts, etc.), diapers, diaper covers, sanitary pants, In addition, sheets (duvet cover, cushion cover, pillow cover, cushion cover, etc.), blankets, mattresses, carpets, carpets, towels, towels, handkerchiefs, gloves, cloth bags, furoshiki, obi (ropes), sanitary cotton, filters It can be used for textile products such as non-woven fabrics such as and wet tissue.
Other applications include plastics, paints,
It can be applied to various products such as adhesives, plumbing and air-conditioning ducts in various factories, tiles in toilets and baths, refrigerators, and holding fruits and vegetables.

[0005]

2. Description of the Related Art So far, sorbic acid, dehydroacetic acid and its salts, and paraoxybenzoic acid derivatives have been widely used as antibacterial and preservatives for foods, pharmaceuticals, cosmetics, etc. due to spoilage and contamination. There are restrictions in terms of sex, and the amount added and target foods are restricted (for example, the upper limit of incorporation of sorbic acid and its salts in food is 0.3%, and dehydroacetic acid and its salts are used in cheese, butter and margarine). Only, and the upper limit of the mixing of methyl sodium paraoxybenzoate in cosmetics was 1.0%).

In addition, in order to suppress the growth of microorganisms that cause decay and contamination, the invasion of microorganisms is suppressed by physical or chemical methods such as distribution of bactericidal substances and mucus on the skin and mucous membranes of living bodies. Furthermore, against invading microorganisms, resistance to innate and non-specific infections, such as inhibition of adhesion by immunoglobulins, phagocytosis by phagocytic cells, and lysis by lysozyme, and immune response to specific pathogens, etc. Is expressed.

[0007] However, if the infectivity of bacteria exceeds the resistance in the living body, infectious symptoms appear in the living body, for example, infectious dermatitis such as pyoderma due to Staphylococcus aureus, food poisoning, sepsis, etc. Bacillus subtilis, conjunctivitis, iritis, Escherichia coli, urinary tract infection, diarrhea, etc.In addition, candidiasis causes vesicles and pustules on the skin, especially the vulva, rarely causes sepsis, meningitis, Trichophyton is a type of dermatophyte and is acne caused by tinea (e.g., phagocytaceae), acne bacteria (Phyrophylactylacterium acnes), and dandruff (Phytophthora porphyra).
There is a risk of causing various symptoms, such as dandruff or Kayumi associated with dandruff.

[0008] Particularly during puberty, acne and dandruff often occur, and acne is called acne vulgaris. Clinically, it is a chronic inflammation that occurs in the pores mainly in the pilosebaceous gland system. Sexual change is defined as dandruff in the scalp,
It is said that keratins of the epidermal layer, secretions of sweat glands and the like are entangled and are caused by enhancement of secretions such as sebaceous glands.

[0009] In view of the cause of acne and dandruff in relation to the ability to secrete sebum, triglyceride in sebum produces lipase due to the invasion of Propionibacterium acnes or Pityrosporum obale into the hair follicle. This increases the production of glycerol and free fatty acids, and the excess free fatty acids generated at this time causes the comedone-forming action and the inflammation-inducing action to be particularly strong.

[0010] Originally, both Propionibacterium acnes and Pityrosporum ovale are lipid-dependent,
In addition, since it is lipophilic, the amount of sebum increases and accumulates in the hair follicle tube, so that Propionibacterium
Acnes and Pityrosporum ovale were also found to grow gradually.In addition, neutrophil chemotaxis and complement activating factors by Propionibacterium acnes and Pityrosporum ovale, as well as the production of the bacteria, were also investigated. The destruction of hair follicle epithelium and the induction of inflammation by biological organisms such as protease, lipase, and hyaluronidase have been proposed as new hypotheses.

Therefore, it is important for the treatment of acne to inhibit the growth of acne bacteria (propionibacterium acnes) at the focus, and to control dandruff or Kayumi associated with dandruff, dandruff at the focus ( It is necessary to prevent the growth of Pitirosporum obale).

Various drugs have been used for preventing and treating infectious diseases inside and outside the body. Antibiotics and synthetic antibacterials and preservatives, which occupy most of them, are certainly effective. There are regulations in terms of safety, and strict attention must be paid to their use, and more effective substances with less side effects have been demanded.

[0013]

Therefore, the present inventors have developed a compound which has a broad antibacterial and antiseptic effect against infectious diseases and diseases caused by bacteria and is safe to use in various fields. Various natural extracts have been studied and new substances and their effects have been studied.

[0014]

Means for Solving the Problems In view of the above circumstances, the present inventors have developed various types of chitosan derivatives obtained by reacting chitosan or a low molecular weight chitosan with a saccharide having a reducing terminal. Bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Klebsiella pneumoniae, black mold, yeast,
Novel antibacterial and antiseptic agents, which are confirmed to have strong antibacterial and antiseptic effects against Trichophyton, acne and dandruff, and are safe for humans and animals, as well as external skin preparations and bath agents It has been found that application to foods, drinks, and fiber treatment agents is extremely effective, and the present invention has been completed. Hereinafter, the process leading to the present invention will be described.

[0015]

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 saccharides 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. Also, disaccharide-polysaccharide saccharides containing these monosaccharides as components, such as maltose, isomaltose, maltotriose, lactose or various oligosaccharides, pullulan, inulin, amylose, amylopectin, dextran, dextrin, starch and other natural polysaccharides 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, 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 the amide bond, the free carboxyl group of these saccharides is reacted with SOCl ₂ , esterified with p-nitrophenol, or acid chlorided with phosphorus pentoxide to form the carboxyl group. 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 terminal, a disaccharide D-galactopyranosyl-gluconic acid is exemplified. 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, it is possible to use a carbodiimide-based coupling agent, for example, N, N-dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (ECC), or the like. 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 may be 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 derivatization rate of the saccharide having a reducing terminal to the 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 can be prepared by arbitrarily drying, concentrating or diluting it according to the type and form of the antibacterial and preservative to be applied, and also the external and external preparations for skin and bath, food and drink, and fiber treatment agent. Good.

The chitosan derivative of the present invention can be used as it is as a novel antibacterial and preservative, and can also be added to skin external preparations, bath preparations, foods and drinks, and fiber treatment agents. However, it differs slightly depending on the type or quality of various uses and the expected degree of action. Usually, it is not less than 0.01 (w / v%), preferably not more than 0.1 (w / v%).
2 (w / v%) or more is good. In addition, the compounding amount is 0.01 (w / v
%), The effect cannot be expected sufficiently.

The antibacterial and preservatives containing the chitosan derivative of the present invention, the skin external preparation and bath preparation, foods and drinks, and the fiber treatment agent may impair the effects of the present invention, if necessary, in addition to the above essential components. Pharmaceuticals, quasi-drugs,
It can be produced by arbitrarily selecting and using components and additives used in preparations such as cosmetics and foods and beverages.

(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, isopiranol, 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, but usually, water or a water-soluble organic solvent (eg, ethanol) ,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.

In addition, 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.

In the case of edible products, health and cosmetic effects such as nutritional supplementation, recovery from fatigue, tonicity, cell activation (prevention of cell aging) and the like, improvement of taste, provision of color tone, aroma and gloss, stabilization, It can be used for thickening and preservation. Furthermore, in addition to this, various cosmetic and pharmaceutical effects of each known raw material are expected, and by combining them, the intended effect is enhanced or multi-functional. It is also possible to make a product that expects an effect.

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, Usubaaonori, Sujiaonori, Hiraaonori, Bouuaonori, Hosoedaaonori], and seaweeds [Brown algae: Macombum, Lyconib, Hosoamebu, Hoshiezobu, Hosoedahon, Hosoeda oni 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.

Also, other algae, for example, green algae (Chlamydomonas: Chlamydomonas, Akayukimo, Dunaliella: Dunaliella, Chlorococcus: Chlorococcus, Kwanomimo: Kwanomimo, Volvox: Ohigemawari, 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.

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 metabolites Yeast metabolites, yeast extract, rice ferment extract, rice bran ferment extract, euglena extract, lactic acid fermentation of skim milk powder, trehalose or derivatives 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 absorbing / blocking agent 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) Whitening agent 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, oxybenzone, benzophenone, arbutin, guaiazulene, shikonin, baicalin, baicalein, berberine and the like.

(19) Tyrosinase activity inhibitor Ascorbic acid and its derivatives, hydroquinone and its glycosides, kojic acid and its derivatives, placental extract, silk peptide, plant extract (mulberry, corn, waremokou, clara, mugwort, honeysuckle, Yellowfin, Dokudami, Matsuhodo, Admiral, Odorikosou, Hop, Hawthorn, Eucalyptus, Yarrow, Althea, Calypt, Mankeishi, Hamamelis, Yamaguwa, Enmeisou, Kikyo, Toshishi, Tsutsukoko, Shako, Mao, Sengoku, Dokkatsu, Psycho, (Boufu, Hamabofu, Ogon, Peony, Peony, Gennoshoko, Kakkon, Licorice, Gobiko, Aloe, Ginger, Safflower, Green Tea, Tea, Asenyaku etc.)

(20) Melanin dye reduction / decomposition Hydroquinone monobenzyl ether, phenylmercury hexachlorophene, mercuric oxide, mercurous chloride, aqueous hydrogen peroxide, zinc peroxide and the like.

(21) 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.)

(22) 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.

(23) Active oxygen scavengers SOD, catalase, glutathione peroxidase and the like.

(24) 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.

(25) 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.)

(26) 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.

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

(28) Humectants 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.

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

(30) 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.

(31) 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.

(32) Flavor 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, Guaiac wood 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.

(33) Dyes and 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.

(34) Sweeteners Sugar, sweet tea, fructose, arabinose, galactose, xylose, mannose, maltose, honey, glucose, miraculin, monelin, licorice extract and the like.

(33) Nutrition enhancer Shell calcined calcium, cyanocolabamine, yeast, wheat germ, egg yolk powder, hemicellulose, heme iron and the like.

(34) Dairy products Milk, cheese, fresh cream, butter, margarine, milk powder, whey, condensed milk and the like.

In addition, humectants, hormones, sequestering agents, pH adjusters, chelating agents, preservatives and anti-binders, fresheners, stabilizers, emulsifiers, animal and vegetable proteins and their decomposed products, animal and vegetable 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 Agent, oral agent, deodorant / deodorant, bittering agent, seasoning, enzyme, anti-recontamination agent such as carboxymethyl cellulose, rinse improver such as soap, anti-caking agent,
Examples include a fluorescent whitening agent, a softener, a bleaching agent, a sizing agent, a stain removal aid and the like, and when used in combination therewith, various additive and synergistic effects can be expected.

The antimicrobial / preservative containing the chitosan derivative of the present invention, the external preparation for skin and bath, the food and drink, and the fiber treatment agent can be in any form, such as ampule, capsule,
Drugs such as pills, tablets, powders, granules, solids, liquids, gels, foams, emulsions, creams, ointments, sheets, etc., quasi-drugs, cosmetics for skin and hair And it can be used by blending in bath agents, foods and drinks, and textiles.

Specifically, for example, pharmaceutical preparations for internal / external use, basic cosmetics such as lotions, emulsions, creams, ointments, lotions, oils, packs, facial cleansers and skin cleansers, shampoos, rinses, and hair treatments , Hair cosmetics such as hair styling agents, perm agents, hair tonics, hair dyes, hair growth and hair restoration, foundations, makeup cosmetics such as lipstick, blusher, eyeshadow, eyeliner, mascara, perfumes, bath agents, etc. , Toothpaste, mouth freshener
Gargle, deodorant / deodorant, sanitary cotton, wet tissue,
It can be applied to various products such as plastics, paints, adhesives, plumbing and air-conditioning ducts in various factories, tiles for toilets and baths, refrigerators, fruits and vegetables.

Examples of foods and drinks include oral compositions (gum, candy, etc.), processed seafood products such as kamaboko and chikuwa, livestock products such as sausage and ham, western confectionery, Japanese confectionery, raw noodles, Chinese noodles, boiled Noodles such as noodles, buckwheat, sauces, soy sauce, sauce, sugar, honey, powdered candy, water syrup, etc., spices such as curry powder, mustard powder, pepper powder, jam, marmalade, chocolate spread, pickles, soy sauce , Sprinkled and processed vegetables and fruits such as canned and bottled vegetables and fruits, dairy products such as cheese, butter, yogurt, fruit juices, vegetable juices, whey drinks, soft drinks, alcoholic beverages, etc.
Use in general foods and drinks such as health foods is raised.

Examples of fiber products treated with a fiber treatment agent include natural fibers such as cotton and hemp, regenerated cellulose fibers such as rayon and polynosic, and fiber products made of blended fibers thereof, for example, yarns and knits. , Non-woven fabrics, non-woven webs, etc., as well as various synthetic fibers (eg, polyester-based, polyamide-based, vinyl-based, benzoate-based synthetic fibers, etc.), animal fibers (eg, wool, silk, etc.),
Alternatively, blended articles, cross-woven or cross-knitted articles, non-woven webs and the like using these fiber products in combination can be raised.

The specific field of application of the fiber treatment agent of the present invention is as a softening agent, a bleaching agent, a sizing agent, a stain removal aid, etc., in the form of general textile products such as clothing (pajamas, Shirts, pants, socks, brassiere, panties, tights, slips, blouses, pants, skirts, etc.), diapers, diaper covers, sanitary pants, and other sheets (duvet covers, cushion covers, pillowcases)
Cushion covers, etc.), blankets, mattresses, carpets, carpets, towels, towels, handkerchiefs, gloves and other nonwoven fabrics such as sanitary cotton, filters and wet tissues, and washing with commonly used detergents It can be used for textile products after it has been made.

The method of adding the antibacterial and preservative of the present invention to the skin external preparation and bath preparation, food and drink, and fiber treatment agent may be added in advance or during the production. It may be appropriately selected in consideration of workability.

[0080]

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. 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 Kagaku Kogyo KK, 85% deacetylation degree), stirred, dispersed, and adjusted to pH 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) Growth Inhibition Test against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Klebsiella pneumoniae [Test bacterial species] Escherichia coli Escherichia coli: (ATCC873
9) 2. 2. Staphylococcus aureus Staphylococcus aureus: (ATCC6538) 3. Staphylococcus aureus Staphylococcus aureus: (ATCC6538P) 4. Shoot Pseudomonas aeruginosa Pseudomonas aeruginosa: (ATCC9027) Bacillus subtilis Bacillus subtilis: (ATCC93
72) 6. Klebsiella pneumoniae Klebsiella pneumoniae: (ATCC4352) [Media used] Brain Heart Infusion Broth (BH)
I) "Eiken" [Preparation of sample bacterial solution] Culture the bacteria used for the test in the above medium
(37 ° C., 18 hours), and diluted with the same medium so that the number of bacteria was 1.0 × 10 ⁵ . [Preparation of sample] Chitosan derivative of the present invention (Production Example 1)
3181 g was dissolved in purified water, made up to 50 ml, and filtered through a 0.45 μm membrane filter to obtain a sample solution. In addition, it carried out similarly about methyl parahydroxybenzoate. [Test Method] Purified water was used as a diluent in advance, and a multiple dilution series of the sample solution was prepared (0.5 ml). 0.4 ml of the above medium and 0.1 ml of the test bacterial solution were added thereto, and the mixture was cultured at 37 ° C for 18 hours.
The MIC (minimum inhibitory concentration) was determined. The results are shown in Table 1.

[0084]

[Table 1]

[Test Results] The chitosan derivative of the present invention has an MIC (minimum inhibitory concentration) of 0.16 w / v% against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis and Klebsiella pneumoniae.
Hereinafter, the growth inhibitory effect could be confirmed even with a small amount against Klebsiella pneumoniae. In addition, even when compared with methyl parahydroxybenzoate used as a control, the same or higher growth inhibitory effect was confirmed. Similarly, the chitosan derivative of the present invention (Production Example 2) was confirmed to have a growth inhibitory effect against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, and Klebsiella pneumoniae, which was almost equivalent to that of Production Example 1. .

(Test 2) Growth Inhibition Test against Black Mold, Candida, Yeast, and Trichophyton [Test Bacteria Species] Aspergillus niger black mold: (AT
CC9642) 2. Candida albicans Candida albicans: (A
TCC10231) 3. 3. Saccharomyces cersvisiae yeast: (IFO0216) Trichophyton rubrum Trichophyton rubrum [Media used] Potato dextrose medium [Preparation of sample bacterial solution] Culture the bacteria used for the test in the above media
(37 ° C., 7 days), and diluted with the same medium so that the number of bacteria was 1.0 × 10 ⁴ . [Preparation of sample] Chitosan derivative of the present invention (Production Example 1)
1564 g was dissolved in purified water, made up to 15 ml, and filtered through a 0.45 μm membrane filter to obtain a sample solution. In addition, it carried out similarly about methyl parahydroxybenzoate. [Test method] Purified water was used as a diluent in advance, a multiple dilution series of the sample solution was prepared (0.5 ml), 0.4 ml of the above medium and 0.1 ml of the test bacterial solution were added, and the mixture was cultured at 37 ° C for 5 days.
The MIC (minimum inhibitory concentration) was determined. The results are shown in Table 2.

[0087]

[Table 2]

[Test Results] The chitosan derivative of the present invention has an MIC (minimum inhibitory concentration) of 0.03 w / v% or less against Candida, yeast and ringworm, and a small amount against black mold. Showed the growth inhibitory effect.
In addition, even when compared with methyl parahydroxybenzoate used as a control, the same growth inhibitory effect was confirmed. Similarly, the chitosan derivative of the present invention (Production Example 2) is also produced against Production of Black Mold, Candida, Yeast, and Trichophyton.
A growth inhibitory effect almost equivalent to that of was confirmed.

(Test 3) Growth inhibition test against Pitirosporum ovale [Test strain] * Pityrosporum ovale (Pityrosporum ovale)
Dandruff fungus [Media used] Potato-glucose medium (Nissui Pharmaceutical) containing 5% ( ^V / _V ) polyoxyethylene glycerol monooleate [Preparation of specimen] Chitosan derivative of the present invention (Production Example 1) .
1 g was dissolved in purified water to make 10 ml, which was filtered through a 0.45 μm membrane filter to obtain a sample solution. In addition, it carried out similarly about methyl parahydroxybenzoate. [Test Method] Samples were dissolved in a medium, and 2 ml of each dilution step was prepared, and the minimum growth inhibitory concentration was measured by the dilution method. In addition, 1.6 × 10 ³ Pityrosporum ovale were inoculated, cultured at 37 ° C. for 48 hours, and MIC (minimum inhibitory concentration).
Was determined. In addition, zinc pyrithione,
The same applies to Octopirox. Table 3 shows the results
It was shown to.

[0090]

[Table 3]

[Test Results] The chitosan derivative of the present invention has an MIC (minimum inhibitory concentration) against dandruff of 0.0
The growth inhibitory effect could be confirmed with a very small amount of 078 w / v% or less. In addition, even when compared with zinc pyrithione and octopirox used as controls, the same or higher growth inhibitory effect was confirmed. Similarly, the chitosan derivative of the present invention (Production Example 2) also showed
A growth inhibitory effect almost equivalent to that of Production Example 1 was confirmed.

(Test 4) Growth Inhibition Test against Propionibacterium acnes [Test Bacteria] * Propionibacteriu
m acnes) Acne [Use medium] 0.3% yeast extract, 0.5% Nutrient Broth,
0.2% Tween 80 [Preparation of Sample] Chitosan derivative of the present invention (Production Example 1)
1 g was dissolved in purified water to make 10 ml, which was filtered through a 0.45 μm membrane filter to obtain a sample solution. In addition, it carried out similarly about methyl parahydroxybenzoate. [Test Method] Samples were dissolved in a medium, and 2 ml of each dilution step was prepared, and the minimum growth inhibitory concentration was measured by the dilution method. 2.0 × 10 ⁷ Propionibacterium acnes were inoculated, anaerobically cultured at 37 ° C. for 7 days, and then MIC (minimum inhibitory concentration) was determined. As a comparative sample, the same procedure was performed for oak extract. The results are shown in Table 4.

[0093]

[Table 4]

[Test Results] The chitosan derivative of the present invention has an MIC (minimum inhibitory concentration) against acne of 0.1%.
The growth inhibitory effect could be confirmed with a very small amount of 0031 w / v%. It should be noted that a very strong growth inhibitory effect was confirmed even when compared with the oat extract used as a control.
Similarly, the growth inhibition effect of the chitosan derivative of the present invention (Production Example 2) was almost the same as that of Production Example 1 against acne bacteria.

(Test 5) Safety test (1) Skin primary irritation test The chitosan derivative of the present invention obtained in Production Examples 1 and 2 was purified water so that the dry solid content was 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 6) Safety test (2) Acute toxicity test Similarly, the chitosan derivative of the present invention obtained in Production Examples 1 and 2 was purified from purified water so that the dry solid 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 antibacterial / preservative, skin external preparation and bath preparation, food and drink, fiber treatment agent The following prescription examples are shown below according to the above evaluation results. And only the compounding amount is shown. Further, the present invention is not limited to these.

(Formulation Example 1) Emulsion Weight% 1. Squalane 6.0 2. Olive oil 6.0 3. Jojoba oil 6.0 4. Cetyl alcohol 1.5 5. Glycerin monostearate 2.0 6. Polyoxyethylene (20) cetyl ether 3.0 7. Poly Oxyethylene (20) soorbitan monooleate 2.0 8.1,3-butylene glycol 1.0 9. Glycerin 2.0 10. 3% aqueous solution of chitosan derivative of Preparation Example 2.0 11. Perfume appropriate amount 12. Purified water 100

(Formulation Example 2) Lotion% by weight 1. Sorbit 2.0 2.1.3-butylene glycol 2.0 3. Polyethylene glycol 1000 1.0 4. Polyoxyethylene oleyl ether (25E.O.) 2.0 5. Ethanol 10.0 6. Production example 2% 5% chitosan derivative aqueous solution 2.0 7. Appropriate amount of pH adjuster 8. Appropriate amount of fragrance 9. Residue to 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% aqueous solution of chitosan derivative of Production Example 1 3.0 7 Appropriate amount of fragrance 8.Purified water 100 residue

(Formulation Example 4) Cold cream weight% 1. Beetle wax 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 fragrance 8. Residue to purified water 100

(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 5. 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% aqueous solution of chitosan derivative of Production Example 2.0 2.0 7. Appropriate amount of pH adjuster 8. Appropriate amount of fragrance 9. Residue to 100 purified water

(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% chitosan derivative aqueous solution of Production Example 1 1.0 6. 2% chitosan derivative 50% ethanol aqueous solution of Production Example 2 2.0 7. Appropriate amount of fragrance 8. Residue to 100 purified water

(Formulation Example 9) Hair tonic% by 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 5% chitosan derivative aqueous solution of Production Example 1, antibiotics, anti-inflammatory, etc., and attached to the wound. Alternatively, a 5% aqueous solution of chitosan derivative may be directly applied locally and covered with gauze or the like.

(Prescription Example 12) Juice drink weight% 1. Glucose liquid sugar 35.0 2. Grapefruit juice 62.7 3. Flavor 2.0 4. Chitosan derivative powder of Production Example 1 0.3 5. Acidulant appropriate amount

(Formulation Example 13) Mentsuyu liquid% by weight 1. Soy sauce 78.0 2. Black vinegar 3.0 3. Glucose 15.0 4. Sodium glutamate 3.0 5. 2% chitosan derivative aqueous solution of Production Example 2 1.0

(Formulation Example 14) Udon or buckwheat wt% 1. Flour or buckwheat flour 97.0 2. Salt 1.0 3. 1% chitosan derivative aqueous solution of Production Example 1 2.0

(Formulation Example 15) Bread wt% 1. Wheat flour 90.5 2. Salt 0.5 3. Glucose 8.6 4. Chitosan derivative powder of Production Example 1 0.2 5. Chitosan derivative powder of Production Example 2 0.2

(Formulation Example 16) Cookie weight% 1. Milk 62.0 2. Whole egg 18.0 3. Sugar 12.5 4. Constarch 6.0 5. Salt 0.5 6. Chitosan derivative powder of Production Example 1 1.0 7. Appropriate amount of flavor

(Formulation Example 17) Gum weight% 1. Menthol micron 33.0 2. Grapefruit flavor 66.0 3. Chitosan derivative powder of Production Example 2 1.0

(Formulation Example 18) Kamaboko weight% 1. Surimi 85.0 2. Starch 9.0 3. Mirin 3.5 4. Sodium glutamate 1.7 5. Salt 0.5 6. Chitosan derivative powder of Production Example 1 0.3

(Test 7) Use effect test The effect when the skin external preparation of the present invention was actually used was examined. As a test, a panel of 20 adult males and females aged 5 to 50 years suffering from acne dermatosis was used as a panel, twice daily in the morning and evening, and after washing the face, an appropriate amount of the emulsion of Formulation Example 1 was applied to the face for 3 months. It was done by doing. In addition, the scalp and hairline also suffer from dandruff skin disease.
A 20-year-old male and female 40-year-old was also subjected to a usage test by applying an appropriate amount of the hair tonic of Formulation Example 9 to the scalp for 3 months after daily hair washing. In contrast,
Emulsions and hair tonics from which the chitosan derivative of the present invention had been removed and formulated in the same manner were used. or,
The evaluation was performed according to the following criteria. The results are as shown in Tables 5 and 6, and the numerical values in the table represent the number of persons. No one complained of abnormalities on the skin or scalp during the use period.

Ineffective: no change from before use. "Effect of improving acne" Effective: Acne was improved. Somewhat effective: acne has been slightly improved. Ineffective: No change from before use.

"Effect of dandruff improvement" Efficacy: Dandruff was improved. Slightly effective: Slightly improved dandruff. Ineffective: No change from before use.

[0119]

[Table 5]

[0120]

[Table 6]

[Test Results] As shown in Tables 5 and 6, the external preparation for skin of the present invention was confirmed to have a good effect on the improvement of skin diseases such as acne and dandruff.

(Test 8) Use Effect Test The effect of the food of the present invention actually used was examined. In the use test, the kamaboko of Prescription Example 18 was left at room temperature to observe changes. A control prepared by removing the chitosan derivative of the present invention from the kamaboko in the same manner was used as a control.

[Test Results] After 10 days, the food of the present invention
No change was observed, but the non-added one was discolored and decomposed, resulting in a spoiled state.

(Test 9) Use effect test The effect when the fiber treating agent of the present invention was actually used was examined. The use test is Shake F, which is adopted when certifying the SEK mark of antibacterial and deodorized textile products
The examination was performed according to the lask method (processing technology VOL. 31, NO. 7, P477-480). The test method was as follows. To a cloth (2.0 g), 3.0 ml of a 0.1% chitosan derivative aqueous solution of the present invention (Preparation Example 1) was added, and the cloth was air-dried.
Based on the k method, the sterilization rates of Staphylococcus aureus (Staphylococcus aureus: ATCC6538P) and Klebsiella pneumoniae (Klebsiella pneumoniae) were determined. The results are shown in Table 7.

[0125]

[Table 7]

[Test Results] The fiber product of the present invention was confirmed to have a very effective sterilizing effect on Staphylococcus aureus and Klebsiella pneumoniae used as general indicators.

[0127]

The chitosan derivative obtained by reacting the chitosan of the present invention with a saccharide having a reducing end can be used for various bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Klebsiella pneumoniae, Against black mold, yeast, ringworm, acne, dandruff) and is safe for humans and animals. Therefore, when used as an antibacterial and preservative, it is possible to prevent spoilage and contamination of various forms of preparations and products. In addition, it has the effect of suppressing dandruff and Kayumi, and can be applied to skin external preparations and bath preparations in the field of pharmaceuticals, quasi-drugs or cosmetics (including various preparations used for humans and other animals). For general foods and drinks, and as a fiber treatment agent, it can be used for general textile products in the form of softeners, bleaching agents, gluing agents, stain removal aids, and other plastics, adhesives, It can be applied to various products such as plumbing and air-conditioning ducts of various factories, tiles for toilets and baths, refrigerators, and holding fruits and vegetables.

────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] December 19, 1997

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0026

[Correction method] Change

[Correction contents]

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

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 7/00 A61K 7/00 W 7/06 7/06 7/075 7/075 7/08 7/08 7/48 7 / 48 7/50 7/50 D06M 15/03 D06M 15/03 (72) Inventor Yoshiharu Matahira 1510-2 Higashicho, Shimada-shi, Shizuoka

Claims (4)

[Claims] (1) An antibacterial / preservative comprising a chitosan derivative obtained by reacting chitosan with a saccharide having a reducing end. 2. An external preparation for skin and a bath preparation, comprising the antibacterial and preservative according to claim 1. (3) A food or drink comprising the antibacterial / preservative according to (1). 4. A fiber treating agent comprising the antibacterial and preservative according to claim 1.