JPWO2009116450A1 - Elastase activity inhibitor - Google Patents

Abstract

An object of the present invention is to provide an inhibitor of elastase activity that is effective in preventing or improving skin appearance problems such as wrinkles, and is safe to use on the skin. The problem is solved by providing an elastase activity inhibitor containing two or more compounds.

Description

  The present invention relates to an elastase activity inhibitor, and more particularly, to an elastase activity inhibitor containing vitamin P as an active ingredient.

  Due to external stimuli such as ultraviolet rays, peroxides, humidity and temperature, mental stress, aging, etc., the skin has reduced water retention function, body temperature maintenance function, immune function and other basic functions, wrinkles and wrinkles (below) In this specification, wrinkles and wrinkles are collectively referred to as “wrinkles”), various cosmetic problems such as formation of dullness, reduced flexibility or elasticity occur.

  Among them, wrinkles are a typical change that affects the aesthetic appearance of the skin, and since they occur with aging, they are one of the major skin problems for older people and women. Although various studies have been conducted to prevent aging due to the aging society, there are few effective methods for improving wrinkles.

  It is said that wrinkle formation is caused by a decrease in the elasticity of the skin, and one of the main causes is a decrease in extracellular matrix components such as collagen and glycosaminoglycan and a change in structure, particularly a decrease in elastin and a change in its structure. ing.

  It is believed that elastin loss and structural changes that occur during the formation of wrinkles are caused by elastase produced and secreted by dermal fibroblasts. Inhibiting the activity of this elastase, suppressing the reduction of elastin and structural modification, maintaining the elasticity and tension of the skin, from the viewpoint of preventing or improving the formation of wrinkles, An elastase activity inhibitor and a cosmetic composition containing the same have been proposed (see, for example, JP-A-2006-219447). However, existing elastase activity inhibitors may not be able to obtain a sufficient anti-wrinkle effect, but may be problematic in terms of irritation.

  On the other hand, in addition to the formation of wrinkles, fat accumulation in the skin progresses excessively with aging due to westernization of the diet, satiety, overeating, lack of exercise, stress, etc., and the aesthetic appearance of the skin It is a factor that damages.

  The prevention and improvement of aesthetic appearance problems due to skin wrinkles and fat accumulation accompanying such aging not only inhibits elastase activity, but also inhibits fat accumulation, inflammation, Furthermore, it is very useful to promote blood circulation in the vicinity of the skin and to activate metabolism (see, for example, JP-A-08-291038 and JP-A-2005-336116). That is, by promoting blood circulation in and around the skin, metabolism of the body is promoted, which is very beneficial for the entire body. For cosmetic purposes, it is possible to improve the color of the skin and prevent dullness of the skin, as well as to improve the metabolism in the skin, the excess subcutaneous fat is decomposed, and the skin tissue has sufficient nutrition and moisture. By being supplied, it becomes possible to maintain a moist and youthful skin, which can prevent skin aging, and its utility is immeasurable.

  In addition, even if only specific factors that impair the aesthetic appearance of the skin are suppressed or improved, a truly satisfactory anti-aging effect on the skin cannot be obtained. Development of safe ingredients that can comprehensively solve the problems of aesthetic appearance of the skin, such as accumulation of skin, is desired.

  On the other hand, hesperidin, rutin and its enzymatic degradation products isoquercitrin, hesperetin, quercetin and the like are known as vitamin P, that is, a vitamin-like substance that suppresses increase in capillary permeability (for example, “ Iwanami Biology Dictionary 4th edition ", Iwanami Shoten Co., Ltd., page 1156 (1996)), however, there is no description that these components affect elastase activity. In addition, these components have low solubility in water and may cause problems when blended into an external preparation for skin. As a means for solving this problem, the water solubility is remarkably high. Improved hesperidin, naringin, rutin and glycosylated products of enzyme degradation products thereof, and compositions containing the same have been proposed (for example, JP-A-08-291038, JP-A-2005-336116, (See Kaihei 04-13691, JP-A-03-7593, JP-A-03-58790, and JP-A-56-156299), but these sugar transfer products have an effect on elastase activity. There is no mention about the effect.

  An object of the present invention is to provide an elastase activity inhibitor that is effective in preventing or improving the appearance problems of skin such as wrinkles and is safe even when used on the skin.

  In view of the above problems, the present inventors have examined components having an elastase activity inhibitory action, and as a result, have found that vitamin P has an excellent action. Furthermore, vitamin P has a slimming action, a blood circulation promoting action and the like, and when used in the form of an external preparation for skin, it has an excellent action for preventing or improving the problem of aesthetic appearance of the skin such as wrinkles on the face and hands. I found out. In addition, vitamin P has a lipase activity inhibiting action, an active oxygen removing action, an anti-inflammatory action, a radical removing action, an in vivo lipid peroxide reducing action and / or an in vivo ascorbic acid reduction inhibiting action, and skin aging. The present invention has been completed by finding the knowledge that it has a physiological activity involved in the inhibition of the above.

  That is, this invention solves the said subject by providing the elastase activity inhibitor containing vitamin P as an active ingredient.

  Vitamin P is a highly safe substance. In addition, one or more of these vitamin Ps are used as active ingredients, and the total amount is 0.001% by mass or more (hereinafter, mass% is expressed as “%” unless otherwise specified). Elastase activity inhibitor prevents skin aging and restores youthful skin condition by suppressing the generation of wrinkles by elastase activity inhibitory action and fat degradation promoting action to restore and maintain skin tension and elasticity. Excellent effect of maintaining Furthermore, an elastase activity inhibitor containing one or more vitamin P is a slimming action, blood circulation promoting action, lipase activity inhibiting action, radical removing action, anti-inflammatory action, whitening action, in vivo lipid peroxide Reduces skin as well as the blood circulation and metabolism in the vicinity and prevents skin dullness, and reduces skin flexibility and elasticity by reducing action and reducing ascorbic acid in vivo. Excellent improvement effect of defects. Among them, glyceryl naringin and glycated hesperidin are excellent in inhibiting elastase activity, and are light in color with no irritation or odor. Therefore, there are fewer restrictions when blended into a topical skin preparation than yellow glycated luciferin. .

  Vitamin P used in the present invention is a vitamin-like substance having an action of suppressing an increase in capillary permeability (hereinafter sometimes referred to as “vitamin P-like substance”), and has an elastase activity inhibitory activity. If it is a substance which has this, there will be no restriction | limiting in particular. Specifically, naringin, hesperidin, rutin, esculin, and their enzymatic degradation products, purnin, β-glucosyl hesperetin, isoquercitrin, naringenin, hesperetin, quercetin, esculetin (hereinafter, purnin, β-glucosyl hesperetin, isoform) Quercitrin, naringenin, hesperetin, quercetin, and esculetin may be collectively referred to as “enzymatic degradation vitamin P”), and these α-glycosyl glycosides. The α-glycosyl glycoside means that one or more molecules of glucose are α-linked, and the binding site may be a part of the aglycon of these substances, and the sugar bound to the aglycon. It may be a part or both. Specifically, glycosylated naringin, transglycosylated hesperidin, transglycosyl rutin, transglycosyl esculin, transglycosylated prnin, transglycosylated β-glucosyl hesperetin, transglycosyl isoquercitrin, transglycosylnaringenin, transglycosyl hesperetin, transglycosylated quercetin, Examples thereof include transglycosyl esculetin (hereinafter, this α-glycosyl glycoside may be collectively referred to as “glycosyl transfer vitamin P”).

  Examples of the glycosylated vitamin P include, for example, α-monoglucosylnarindin, α-diglucosylnarindin, α-triglucosylnarindin, α-tetraglucosylnarindin, α-pentaglucosylnarindin, α-monoglucosylnarindin, α-monoglucosylpurinin, α-di Glucosylpurnin, α-triglucosylpurnin, α-tetraglucosylpurnin, α-pentaglucosylpurnin, α-monoglucosylnaringenin, α-diglucosylnaringenin, α-triglucosylnaringenin, α-tetraglucosylnaringenin, α -Pentaglucosylnaringenin, α-monoglucosyl hesperidin, α-diglucosyl hesperidin, α-triglucosyl hesperidin, α-tetraglucosyl hesperidin, α-pentaglucosyl hesperidin, α-monoglucosyl β-g Cosyl hesperetin, α-diglucosyl β-glucosyl hesperetin, α-triglucosyl β-glucosyl hesperetin, α-tetraglucosyl β-glucosyl hesperetin, α-pentaglucosyl β-glucosyl hesperetin, α-monoglucosyl hesperetin, α-diglucosyl hesperetin , Α-triglucosyl hesperetin, α-tetraglucosyl hesperetin, α-pentaglucosyl hesperetin, α-monoglucosyl rutin, α-diglucosyl rutin, α-triglucosyl rutin, α-tetraglucosyl rutin, α-pentaglucosyl rutin, α -Monoglucosyl isoquercitrin, α-diglucosyl isoquercitrin, α-triglucosyl isoquercitrin, α-tetraglucosyl isoquercitrin, α-pentaglucosyl isoquercitrin α-monoglucosyl quercetin, α-diglucosyl quercetin, α-triglucosyl quercetin, α-tetraglucosyl quercetin, α-pentaglucosyl quercetin, α-monoglucosyl esculin, α-diglucosyl esculin, α-triglucosyl esculin , Α-tetraglucosyl esculin, α-pentaglucosyl esculin, α-monoglucosyl esculetin, α-diglucosyl esculetin, α-triglucosyl esculetin, α-tetraglucosyl esculetin and α-pentaglucosyl esculetin Can be mentioned.

  These glycosylated vitamin P can be prepared by an enzymatic method. Moreover, a fermentation method and a synthesis method can also be utilized as needed. In the case of producing glycosyl transfer vitamin P, an enzyme method using glycosyltransferase is advantageous if economic efficiency is a problem. For example, JP 04-13691 A, JP 03-7593 A, Α-glucosyl such as partially hydrolyzed starch and maltooligosaccharide disclosed in Kaihei 03-58790, JP-A-56-156299, JP-A-2007-284393, JP-A-2007-39349, etc. According to the method of allowing glycosyltransferases such as α-glucosidase, cyclomaltodextrin / glucanotransferase and α-amylase to act on naringin, hesperidin, rutin, esculin and enzymatically degraded vitamin P in the presence of a sugar compound Glucose transfer vitamin P is obtained in high yield. The reaction product thus obtained usually contains a series of glycosylated vitamin Ps whose main components are distributed in the range of 1 to 5 in the degree of glucose polymerization at the transfer part. It is also advantageous to prepare α-monoglucosylvitamin P by allowing glucoamylase to act on this series of glycosylated vitamin P. In the present invention, the glycosylated vitamin P is not necessarily highly purified as long as its physiological function can be exerted, and is an enzyme reaction solution itself as long as its effect and safety are not affected. Alternatively, it may be in the form of an unseparated composition with other substances peculiar to the preparation method including vitamin P, and may be partially purified or highly purified. In particular, when glycosylated vitamin P and unreacted naringin, hesperidin, rutin, esculin, and enzyme-decomposed vitamin P coexist, these vitamin P together exert physiological activities such as elastase activity inhibitory action. And in the presence of glycosylated vitamin P, the solubility of other vitamin P in water is also improved, which is effective in enhancing the physiological action of the elastase activity inhibitor of the present invention.

  In addition, purnin, β-glucosyl hesperetin and isoquercitrin can cause rhamnosidase to act on naringin, hesperidin or rutin as disclosed in, for example, JP 2007-284393 A and JP 2007-39349 A. Can be prepared. Furthermore, aglycones such as naringenin, hesperetin, quercetin, and esculetin can be prepared by allowing rhamnosidase and β-glucosidase to act on naringin, hesperidin, rutin, and esculin. Moreover, it is also optional to prepare these enzyme-decomposed vitamin P using a fermentation method, a chemical decomposition method, or a synthesis method as necessary.

  The elastase activity inhibitor of the present invention may use vitamin P alone, but if two or more of them are used in combination, the physiological action of vitamin P, including elastase activity inhibitory action, is synergistically enhanced. can do. From the viewpoint of the elastase activity inhibitory action and the high solubility in water, glycosylated vitamin P is desirable, and glycosylated naringin and glycosylated hesperidin are particularly desirable. Among transglycosylated naringins, α-monoglucosylnarindine is particularly desirable, and among transglycosylated hesperidins, α-monoglucosylhesperidin is particularly desirable.

  The blending amount of vitamin P in the elastase activity inhibitor of the present invention is appropriately selected depending on the specific form of the inhibitor and the balance with other blending components, as long as the desired effect of the present invention can be obtained. There is no particular limitation. The elastase activity inhibitor of the present invention is usually provided in the form of an external preparation for skin and includes the form of oral intake. In addition to the elastase activity inhibitory action, all vitamin P used in the present invention is slimming action, blood circulation promoting action, lipase activity inhibiting action, radical removing action, anti-inflammatory action, whitening action, in vivo lipid peroxide reducing action Since it exhibits an action to reduce ascorbic acid in vivo, an action to remove active oxygen, etc., in the external preparation for skin of this invention, one or more kinds of vitamin P having the action as exemplified above are effective as a whole. As long as the amount is included.

  Usually, when the elastase activity inhibitor of the present invention is in the form of an external preparation for skin, the blending ratio of vitamin P is generally 0.001 to 10 in total with respect to the total mass of the elastase activity inhibitor. 0.0%, preferably 0.01 to 10.0%, particularly preferably 0.05 to 5.0%. If the blending amount is less than 0.001% with respect to the total mass of the elastase activity inhibitor, the elastase activity inhibitory action and other physiological functions of the active ingredient may not be sufficiently exhibited, which may be undesirable. On the other hand, if it exceeds 10.0%, the tendency to disturb the physical properties of the preparation becomes remarkable, which may not be preferable.

  It is possible to mix | blend a well-known component with the elastase activity inhibitor of this invention according to the specific form. That is, in the case of the external preparation for skin, one or more components that can be used for the external preparation for skin can be usually blended within a range that does not impair the intended effect of the present invention. For example, oil components, surfactants, preservatives (antibacterial agents), fragrances, whitening agents, moisturizers, thickeners, antioxidants, chelating agents, UV absorbers / scattering agents, vitamins, amino acids, anti-inflammatory agents , Blood circulation promoter, seaweed extract, astringent, anti-wrinkle agent, cell activator, anti-aging agent, hair growth / hair growth agent, transdermal absorption promoter, water, alcohols, water-soluble polymer, pH adjuster , Foaming agents, powders, pharmaceuticals, quasi-drugs, cosmetics, food additives, active ingredients for pharmaceuticals, quasi-drugs, etc. May be manufactured.

  Specifically, as oil components, macadamia nut oil, castor oil, olive oil, cacao oil, coconut oil, palm oil, tree wax, jojoba oil, grape seed oil, avocado oil and other vegetable oils, mink oil, egg yolk oil, etc. Animal fats, waxes such as beeswax, whale wax, lanolin, carnauba wax, candelilla wax, hydrocarbons such as liquid paraffin, squalane, microcrystalline wax, ceresin wax, paraffin wax, petrolatum, capric acid, myristic acid Natural and synthetic fatty acids such as palmitic acid, stearic acid, behenic acid, lanolin fatty acid, linoleic acid, linolenic acid, lauric acid, myristic acid, oleic acid, isostearic acid, cetanol, stearyl alcohol, hexyl decanol, octyldodecanol, lauryl Alcoa And natural and synthetic higher alcohols such as capryl alcohol, myristyl alcohol, cetyl alcohol, cholesterol, phytosterol, and esters such as isopropyl myristate, isopropyl palmitate, octyldodecyl myristate, octyldodecyl oleate, cholesterol oleate, etc. be able to.

  Surfactants include sorbitan monolaurate, sorbitan monopalmitate, sorbitan sesquioleate, sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyoxethylene sorbitan monostearate, polyethylene glycol monooleate, polyethylene glycol alkylate, Nonionic surfactants such as polyoxyethylene alkyl ether, polyglycol diether, lauroyl diethanol amide, fatty acid isopropanol amide, maltitol hydroxy fatty acid ether, alkylated polysaccharide, alkyl glucoside, sugar ester, lipophilic glycerin monostearate Self-emulsifying glycerin monostearate, polyglycerin monostearate, polyglycerin alkylate, so Vitan monooleate, polyethylene glycol monostearate, polyoxyethylene sorbitan monooleate, polyoxyethylene cetyl ether, polyoxyethylenated sterol, polyoxyethylenated lanolin, polyoxyethylenated beeswax, polyoxyethylene hydrogenated castor oil, etc. Nonionic surfactant, sodium stearate, potassium palmitate, cetyl sulfate, sodium lauryl phosphate, triethanolamine palmitate, sodium polyoxyethylene lauryl phosphate, sodium N-acyl glutamate, sodium palmitate, sodium laurate, Sodium laurate, potassium lauryl sulfate, alkyl sulfate triethanolamine ether, funnel oil, linear dodecyl benzene sulfate, polio Anionic surfactants such as siethylene hydrogenated castor oil maleic acid, acylmethyltaurine, cationic surfactants such as stearyldimethylbenzylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide, alkyl hydrochloride Examples include amphoteric surfactants such as aminoethylglycine solution and lecithin.

  Preservatives (antibacterial agents) include benzoic acid and its salts, salicylic acid and its salts, sorbic acid and its salts, dehydroacetic acid and its salts, paraoxybenzoic acid alkyl esters and other paraoxybenzoic acid esters, 2, 4, 4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorocarbanilide, hexachlorophene, benzalkonium chloride, phenoxyethanol, hinokitiol, resorcinol, ethanol, 1,3-butylene glycol, photosensitizer 201 Etc. can be illustrated.

  As fragrances, benzaldehyde, benzyl benzoate, phenylacetic acid, sandalol, eugenol, rillial, rilal, linalool, 2-methyl-3- (4-methylphenyl) -propanal, musk ketone, cinnamic aldehyde, belt fix, methyl ionone, Geranylformate, iso-E super, γ-undecalactone, hexyl salicylate, cis-3-hexenyl salicylate, methyl dihydrojasmonate, tetrahydrofurfuryl 3-mercaptopropionate, covanol, vanillin, vanillar, geranium oil, peni Examples include royal oil, birch oil, and alumois oil.

  Examples of whitening agents include L-ascorbic acid and derivatives thereof and salts thereof, alkoxysalicylic acids and salts thereof, hydroquinone derivatives such as hydroquinone and glycosides thereof, tranexamic acid and derivatives thereof and salts thereof, derivatives of resorcin, Examples include kojic acid and derivatives thereof and salts thereof, ellagic acid and linoleic acid and salts thereof, chamomile extract, tetrahydrocurcuminoid, and cyanobacteria extract.

  As the humectant, polyhydric alcohols such as erythritol, xylitol, sorbitol, maltitol, glycerin, propylene glycol, 1,3-butylene glycol, polyglycerin, polyethylene glycol, dipropylene glycol, 1,2-pentanediol, isoprene glycol, etc. , Glucose, maltose, trehalose, carbohydrate derivatives of trehalose, dextrin, cyclodextrin, cyclo {→ 6) -α-D-glucopyranosyl- (1 → 3) -α disclosed in WO 02/10361 -D-glucopyranosyl- (1 → 6) -α-D-glucopyranosyl- (1 → 3) -α-D-glucopyranosyl- (1 →} cyclic tetrasaccharide (cyclonigerosylnigerose: Cyclonigerosylniig) erose), cyclo {→ 6) -α-D-glucopyranosyl- (1 → 4) -α-D-glucopyranosyl- (1 → 6) -α-D-glucopyranosyl- ( 1 → 4) -α-D-glucopyranosyl- (1 →} cyclic tetrasaccharide (cyclomaltosylmaltose) and other sugars, amino acids, NMF components such as sodium lactate and sodium pyrrolidonecarboxylate (natural moisturizing) Ingredients), glycogen, locust bean gum, xyloglucan, quince seed, carrageenan, pectin, mannan, curdlan, succinoglucan, galactan, dermatan sulfate, keratan sulfate, chondroitin, chondroitin sulfate, mucoitin sulfate, keratosulfate, chitin, hepa Mucopolysaccharides such as sulfuric acid and hyaluronic acid, hydrolysates of these mucopolysaccharides, water-soluble polymer substances such as proteins and peptides such as silk and collagen, and hydrolysates thereof, salts thereof, dimethylpolysiloxane, Examples include silicones such as methylphenylsiloxane, culture supernatants such as lactic acid bacteria and bifidobacteria, among others, trehalose, trehalose carbohydrate derivatives, cyclic tetrasaccharides, hyaluronic acid and chondroitin, which have a strong moisturizing effect. It is desirable to use one or two or more selected from sulfuric acid, its salts and hydrolysates.

  Thickeners include sodium alginate, xanthan gum, aluminum silicate, quince seed extract, gum arabic, hydroxyethyl guar gum, carboxymethyl guar gum, guar gum, dextran, tragacanth gum, starch, pullulan, chitin, chitosan, agar, cellulose, etc. Natural synthetic materials such as hydroxypropylcellulose, methylhydroxypropylcellulose, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, soluble starch, cationized cellulose, carboxymethylchitin, semi-synthetic polymer materials, carboxyvinyl polymer, polyvinyl alcohol, polyvinylpyrrolidone Examples thereof include synthetic polymer substances such as vinyl alcohol / vinyl acetate copolymer.

  Examples of the antioxidant include dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, L-ascorbic acid, vitamin E, catechins, flavonoids and derivatives thereof.

  Examples of chelating agents include disodium edetate, ethylenediaminetetraacetate, pyrophosphate, hexametaphosphate, citric acid, tartaric acid, gluconic acid, and the like.

  Examples of the pH adjuster include sodium hydroxide, potassium hydroxide, triethanolamine, nitrilotriethanol, citric acid, sodium citrate, boric acid, borax, and potassium hydrogen phosphate.

  Examples of ultraviolet absorbers / scatterers include paraaminobenzoic acid ultraviolet absorbers, anthranilic acid ultraviolet absorbers, salicylic acid ultraviolet absorbers, cinnamic acid ultraviolet absorbers, benzophenone ultraviolet absorbers, sugar ultraviolet absorbers, 3 -(4'-methylbenzylidene) -d-camphor, 3-benzylidene-d, 1-camphor, urocanic acid, urocanic acid ethyl ester, 2-phenyl-5-methylbenzoxazole, 2,2'-hydroxy-5 -Methylphenylbenzotriazole, 2- (2'-hydroxy-5'-t-octylphenyl) benzotriazole, 2- (2'-hydroxy-5'-methylphenylbenzotriazole), dibenzalazine, dianisoylmethane, 4-methoxy -4'-t-butyldibenzoylmethane, 5- (3,3-dimethyl-2 Norbornylidene) -3-pentan-2-one, 2-hydroxy-4-methoxybenzophenone, octyl dimethyl p-aminobenzoate, ethylhexyl p-methoxycinnamate Saina formate, can be exemplified titanium oxide, kaolin, talc and the like.

As vitamins, vitamin A and its derivatives, vitamin B ₁ and its derivatives, vitamin B ₂ and its derivatives, vitamin B ₆ hydrochloride, vitamin B ₆ tripalmitate, vitamin B ₆ dioctanoate, vitamin B ₁₂ , vitamin B ₁₅ And vitamin B such as derivatives thereof, L-ascorbic acid and derivatives thereof, α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E acetates such as vitamin E acetate, vitamin D, vitamin H, pantothenic acid, panthetin, Examples include flavonoids other than vitamin F, vitamin K, and vitamin P and derivatives thereof, vitamin U, ferulic acid, γ-oryzanol, α-lipoic acid, orotic acid, coenzyme Q10, and derivatives thereof. It may be a salt of Among them, L-ascorbic acid and its derivatives are desirable because they have a strong effect of enhancing the physiological action of vitamin P and the action of enhancing collagen production, which is strongly involved in the suppression of the generation of skin wrinkles. In this respect, a glycoside of L-ascorbic acid is desirable, and L-ascorbic acid-2-glucoside is particularly desirable. The amount of ascorbic acid compounded in the elastase activity inhibitor of the present invention is not particularly limited as long as it is an amount capable of enhancing the physiological activity of vitamin P, and is usually 0.01 to 100% with respect to glycosylated vitamin P, Desirably, 0.05 to 20%, particularly desirably 0.1 to 10%, may be blended.

  Amino acids include glycine, alanine, valine, leucine, isoleucine, serine, threonine, phenylalanine, tyrosine, asparagine, glutamine, taurine, tryptophan, cystine, cysteine, methionine, proline, hydroxyproline, aspartic acid, glutamic acid, arginine, histidine. , Lysine, carnitine, citrulline and derivatives thereof, and salts thereof may be used.

  Anti-inflammatory agents include allantoin or its derivatives, allantoin acetyl-dl-methionine, allantoin chlorohydroxyaluminum, allantoin dihydroxyaluminum, allantoin polygalacturonic acid, glycyrrhetinic acid or its derivatives glycyrrhetic acid, glycyrrhizic acid, glycyrrhetic acid allantoin, Glycyrrhetinic acid glycerin, glycyrrhetinic acid stearyl, stearic acid glycyrrhizintinyl, 3-succinyloxyglycyrrhetinic acid disodium salt, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc. Pantothenyl ethyl ether, pantothenic acid calcium , Pantothenic acid sodium, acetyl pantothenyl ethyl ether, benzoic acid pantothenyl ethyl ether ester, pantothenic acid derivatives such as panthetin, vitamin E, d-δ-tocopherol, dl-α-tocopherol, dl-α-tocopherol acetate, Vitamin E derivatives such as linoleic acid dl-α-tocopherol, nicotinic acid dl-α-tocopherol, succinic acid dl-α-tocopherol, L-ascorbic acid glycosides such as L-ascorbic acid, L-ascorbic acid-2-glucoside, Tetrahexyldecanoic acid ascorbic acid, ascorbic acid-tocopherol phosphate diester in which L-ascorbic acid and tocopherol are bonded via a phosphate group, L-ascorbic acid sulfate, ascorbyl dipalmitate, palmi L-ascorbic acid derivatives such as ascorbyl acid, stearyl ascorbate, L-ascorbyl phosphate, ethyl L-ascorbate, acylated derivatives of L-ascorbic acid derivatives and / or their alkali metals or alkaline earths Metal salts, pyridoxine hydrochloride, menthol, biotin, camphor, turpentine oil, zinc oxide, azulene, guaiazulene and derivatives thereof, mefenamic acid and derivatives thereof, phenylbutazone and derivatives thereof, indomethacin and derivatives thereof, ibuprofen and derivatives thereof, ketoprofen And derivatives thereof, ε-aminocaproic acid, diclofenac sodium, diphenhydramine, tranexamic acid and derivatives thereof, dexamethasone, cortisone and esters thereof, hydrocortisone and esters thereof, Adrenal cortex hormones such as rednisone and prednisolone, antihistamines, Acacia catechu, Achacha, Altea, Arnica, Aloe, Ibutrano, Nettle, Ages, Echinacea, Prunus, Turmeric, Ogon, Oubak, Barley, Hypericum, Ogiri, Mogura , Licorice, cucumber, goldfish, gardenia, kumazasa, watercress, gentiana, ganoderma burdock, burdock, comfrey, khakahi, salvia, salamander, cyantro, licorice, peonies, birch, birch, sage, hypericum, quail Achillea millefolium, Atlantic mint, Senkyu, Assembly, Sakuhaku, Taiso, Thyme, Chinese parsley, Capsicum, Toki, Toki Sengka, Tonin, Dokudami, Tormentilla, Tadeai, Cha, Toki, Tokinsenka, Elderberry, Carrot, Parsley, Hakka, Sandalwood, Loquat, Butcher Bloom, Grape, Broccoli, Safflower, Butterfly, Bodhi, Button, Marronie, Mullock, Peach, Ingredients such as plants or extracts derived from plants such as cornflower, eucalyptus, mugwort, bayberry, lavender, roman chamomile and rosemary can be exemplified.

  As seaweed extracts, there are extracts from brown algae, red algae, green algae, cyanobacteria, etc., specifically, kombu, macombu, wakame, hijiki, cypress, coral, palmaria, tsunomata, nori, aosa, anaaaosa, ascophyllum, Examples include extracts from Hibamata, Mozuku, Okinawa Mozuku, Himantaria and the like. This includes extracts from water plants such as sea cucumbers.

  In addition to the above, plant and animal ingredients such as propolis, herbs, and royal jelly, ingredients such as extracts derived from them, minerals such as deep sea water, bitter and bitter ingredients, antibiotics, calcium hydrogen phosphate , Organic modified montmorillonite, silicic acid, anhydrous silicic acid, magnesium silicate, mica, bentonite, titanium coated mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, calcium carbonate, magnesium carbonate, iron oxide, ultramarine, bitumen, Inorganic powders such as chromium oxide, calamine, zeolite and carbon black, polyamide, polyester, polyethylene, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluorine resin, silicon resin, acrylic acid resin, melamine resin, epoxy resin , Carbonate resin, divinylbenzene / styrene copolymer, copolymer composed of two or more monomers of the above compounds, organic powder such as cellulose, safflower dye, gardenia dye, sicon dye, cochineal dye, Natural colorants such as anthraquinone, anthocyanin, chalcone, and carotenoid dyes, photosensitive elements 101, 201, 301, 401, red 201, 202 Organic pigment powders such as Red 204, Red 205, Red 220, Red 226, Red 228, Red 405, Orange 203, Orange 204, Yellow 204, Yellow 401 and Blue 404, Red No. 3, Red No. 104, Red No. 106, Red No. 227, Red No. 230, Red No. 401, Red No. 505, Orange 20 No. 4, yellow No. 4, yellow No. 5, yellow No. 202, yellow No. 203, green No. 3 and blue No. 1, organic pigment powder such as zirconium, barium or aluminum lake, the above organic powder, Examples thereof include colorants such as natural colorants and organic synthetic dyes, and powders loaded with functional components such as sugar-transferred glycyrrhizin and glycyrrhizin.

  Among the above-mentioned components that can be blended, cyanobacteria extract, cyclonigerosyl nigerose, L-ascorbic acid-2-glucoside, and photosensitizer 101 have the effect of enhancing the physiological activity of the elastase activity inhibitor of the present invention. It is particularly desirable because it is strong. The amount of these components to be incorporated into the elastase activity inhibitor of the present invention is not particularly limited as long as these components are capable of physiological function of vitamin P. Usually, indigo extract (when containing 1.5% solid content derived from indigo plant), cyclonigerosyl nigerose and L-ascorbic acid-2-glucoside are added to the total mass of the elastase activity inhibitor of the present invention. On the other hand, 0.001 to 10% may be blended, 0.05 to 5% is desirable, and 0.1 to 5% is particularly desirable. Photosensitizer 101 may be added in an amount of 0.000001 to 2%, preferably 0.00001 to 0.1%, and preferably 0.0005 to 0.005% based on the total mass of the elastase activity inhibitor of the present invention. 5% is particularly desirable.

  There are no particular limitations on the dosage form when the elastase activity inhibitor of the present invention is used in the form of an external preparation for skin, for example, aqueous solution system, solubilization system, emulsion system, powder dispersion system, solid stick system, water-oil two layers The present invention can be applied in various dosage forms such as a system, a water-oil-powder three-layer system, and the like. Further, the specific form is not particularly limited, and the specific form is not restricted by the distinction in the Pharmaceutical Affairs Law such as cosmetics, pharmaceuticals, and quasi drugs. The external preparation for skin refers to cosmetics, pharmaceuticals, quasi-drugs, and those applied to the skin, the outer skin such as the lips and the scalp, and the oral cavity, specifically, ointments, creams, emulsions, lotions, essences, Jelly, gel, pack, shampoo, rinse, hair treatment, mask, mascara, eyeliner, hair restorer, lipstick (lipstick), lip gloss, foundation, blusher, eye shadow, powder, nail polish, soap, body soap, bath preparation Examples thereof include powder toothpaste, moisturizing toothpaste, toothpaste, water toothpaste, medicated toothpaste, mouth refreshing agent, mouth refreshing film, mouthwash, mouthwash and the like. Also, whitening, beautiful skin, slimming, blood circulation promotion, anti-inflammatory, maintaining gum tension and elasticity, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression, body fat reducing agent, fatigue recovery, stress reduction, sleep quality Also included are compositions for oral consumption such as gums, candy, supplements, and drinks used for the purpose of improving the quality of food.

  The elastase activity inhibitor of the present invention includes anti-wrinkle skin external preparations, slimming promotion skin external preparations, blood circulation promoting skin external preparations, lipase activity inhibiting skin external preparations, anti-inflammatory skin external preparations, radical removal agents Skin preparations for external use, skin preparations for whitening, skin preparations for reducing lipid peroxides in vivo, skin preparations for reducing ascorbic acid in vivo, skin preparations for preventing aging, skin preparations for preventing dull skin and lips It can also be used as a skin preparation for skin, a skin external preparation for hair, an anti-inflammatory skin external preparation, a makeup cosmetic, a skin external preparation for massage, and the like.

  Even when the elastase activity inhibitor of the present invention is used as a composition for oral intake, the same effects as those when used as an external preparation for skin can be obtained. There is no particular limitation on the dosage form in that case, and it may be in the form of solid, powder, granule, tablet, liquid, syrup, paste, milky lotion, capsule, etc. or mixed with normal food and drink. Is also optional. In the case of an elastase activity inhibitor for oral intake, the blending ratio of one or more vitamin P is generally 0% in total with respect to the total mass of the elastase activity inhibitor. .1% or more, preferably 0.5% or more, particularly preferably 1% or more. If the blending amount is less than 0.1% with respect to the total mass of the elastase activity inhibitor, the elastase activity inhibitory action and other physiological functions of the active ingredient may not be sufficiently exerted, which may be undesirable. The upper limit of the blending ratio is not particularly limited as long as it does not affect the physical properties of the target composition for oral consumption. Vitamin P is blended for the purpose of strengthening in the hope of various physiological activities as described above. If it exists, it can also be implemented advantageously to use vitamin P as it is. When the elastase activity inhibitor of the present invention is orally ingested, the daily intake is not particularly limited as long as the elastase activity inhibitory action is exerted. Usually, vitamin P is added in a total amount of 0.05 to 50 g. Preferably, it is 0.1 to 10 g, particularly preferably 0.25 to 5 g. If the dose is less than 0.05 g per day, the desired effect may not be obtained, and if the dose exceeds 50 g, the effect corresponding to the intake may not be obtained.

  Hereinafter, the present invention will be described more specifically by experiments.

<Experiment 1: Effect of vitamin P on elastase activity>
An experiment for examining the effect of vitamin P on the elastase activity was performed as follows. That is, as glycosylated vitamin P, as shown in Table 1, glycosylated naringin, glycosylated hesperidin, and glycosylated rutin (all prepared by Hayashibara Biochemical Laboratories, Inc., purity of 95% or more as α-monoglucosyl vitamin P) )It was used. In addition, naringin, purnin, hesperidin, β-monoglucosyl hesperetin, rutin and isoquercitrin shown in Table 1 have extremely low solubility in water. Therefore, in order to increase the solubility, glycosylated vitamin P is added, Naringin or purnin and glycosylated naringin, hesperidin or β-monoglucosyl hesperetin and glycosylated hesperidin, or vitamin P containing rutin or isoquercitrin and glycosylated rutin were prepared and used (any Is also prepared by Hayashibara Biochemical Laboratories Co., Ltd., purity of 95% or more as vitamin P). Furthermore, vitamin P (both prepared by Hayashibara Biochemical Laboratories Co., Ltd., purity of 95% or more as vitamin P) prepared by blending glycosylated naringin and glycosylated hesperidin or glycosylated rutin was used. As the preparation containing two types of vitamin P, a preparation prepared by mixing approximately equimolar amounts of each was used. Each of these powder preparations containing one or two vitamin Ps in an approximately equimolar proportion was diluted with purified water to a vitamin P content of 6.75 nM. Three-fold serial dilution was performed to prepare a test sample having a molar concentration shown in Table 1 (as a solid, vitamin P concentration was about 0.01 to about 5 mg / ml). To 50 μl of any of these test samples, 20 μM synthetic substrate N-Methoxysuccinyl-L-Alanyl-L-Prolyl-L-Valine-4-Methyl-Cumary-7-Amide (Peptide Institute, Inc.) 25 μl of 0.2 M Tris-HCl buffer solution (pH 8.5, containing 1% bovine serum albumin (BSA) and 1 M NaCl) containing 0.048 units / ml of elastase derived from human neutrophils. 25 μl of 2M Tris-HCl buffer was added and stirred, and reacted at 37 ° C. for 60 minutes. Then, the fluorescence intensity is measured with a fluorescence microplate reader (BIO-TEK INSTRUMENT, trade name “Fluoroscan II”), which measures the amount of 4-nitroaniline, which is a degradation product of the enzymatic reaction by elastase. (Ex 355 nm, Em 460 nm) was measured. Table 1 also shows the results of calculating the inhibition rate (%) of elastase activity according to the following formula based on this measured value. Note that compositions containing almost equimolar amounts of naringenin or purnin and glycosylated naringin, hesperetin or β-monoglucosyl hesperetin and glycosylated hesperidin, and quercetin or isoquercitrin and glycosylated rutin are disclosed in JP-A-2007-284393, respectively. No. 2007-39349, Japanese Patent No. 3155466, and the like.
<Calculation method of elastase activity inhibition rate>
Elastase activity inhibition rate (%) = 100 − [{(B−A) ÷ C} × 100]
A: Fluorescence intensity when no elastase is added B: Fluorescence intensity when elastase and test sample are added C: Fluorescence intensity when only elastase is added <Vitamin P concentration that inhibits elastase activity by 50%>
Among the concentrations of vitamin P used in the measurement, a linear expression showing the relationship between the concentration and the inhibition rate between two points across the concentration that inhibits elastase activity by 50% is obtained, and the concentration of vitamin P that inhibits 50% is obtained by calculation. It was.

  As apparent from Table 1, inhibition of elastase activity dependent on vitamin P concentration was observed when any vitamin P was added and the enzyme reaction was carried out. In addition, when adding naringin or purnin and glycosylated naringin, adding only glycosylated naringin, adding hesperidin or β-monoglucosyl hesperetin and glycosylated hesperidin, and adding only glycosylated hesperidin, or When the concentration at which elastase activity is suppressed by 50% is compared between the addition of rutin or isoquercitrin and glycosyl transfer rutin and the addition of glycosyl transfer rutin alone, the equimolarity of vitamin P in each case is In spite of the addition, a strong inhibition of elastase activity was observed when only the glycosylated product was added even if the concentration was low. In addition, when transglycosylated naringin and transglycosyl hesperidin or transglycosyl rutin were added in an approximately equimolar mixture, strong inhibition of elastase activity was observed at a lower concentration than when each was used alone. It was. Furthermore, among the sugar-transferred vitamin Ps tested, the strongest elastase activity inhibitory action was observed when a test sample in which sugar-transferred naringin or sugar-transferred hesperidin or these two types of vitamin P were mixed was added. Since elastase degrades elastin and reduces the amount of elastin in the dermis, causing wrinkles (for example, see JP-A-2006-219447), this result shows that vitamin P forms wrinkles. It is useful as an active ingredient of an elastase activity inhibitor for suppressing the above. In addition, transglycosylated vitamin P has superior anti-wrinkle action than non-glycosylated vitamin P. Among them, glycosylated naringin and transglycosylated hesperidin have particularly strong anti-wrinkle action. Tells.

<Experiment 2: Effect of Glucose Transfer Vitamin P on Wrinkle Formation>
In Experiment 1, since a strong elastase activity inhibitory action was found on glycosylated vitamin P, a test was conducted to examine the effect of glycosylated vitamin P on the formation of wrinkles involving elastase activity as follows. That is, as in the formulation shown in Table 2, glycosylated vitamin P blended cream (test samples 1 to 3) blended with glycosylated naringin, glycosylated hesperidin or glycosylated rutin, glycosylated naringin, and glycosylated hesperidin or sugar Glucose transfer vitamin P-containing cream containing transfer rutin (test samples 4 to 5) and cream not containing sugar transfer vitamin P (control) were prepared. Note that the amount of vitamin P blended is such that the total is approximately equimolar in each test sample, and in the test sample blended with two types of vitamin P, two types of vitamin P are approximately equimolar. It was. Ninety volunteer women (35 to 55 years old) were randomly divided into 6 groups of 15 subjects as subjects, and each of the 15 subjects in each of the 5 groups was given one of the test samples and the remaining 15 in 1 group. The control cream was applied evenly to the face twice a day for 90 days every day. Before application, on the 45th and 90th day of application, place a circular cup on the site specified from the position of the corner of the eye and the ear, apply medical silicon, and prepare a skin replica with a diameter of 20 mm. did. Wrinkle reduction rate (%) calculated according to the following formula was measured by using an optical profilometer to measure the degree of unevenness of the replica of the test sample or control of each subject before application, 45 days after application, and 90 days after application. It shows together in Table 2. The subjects were instructed not to expose their face excessively to direct sunlight from 4 days before the start of the test to the end of the test.
<Calculation method of wrinkle reduction rate>
Wrinkle reduction rate (%) = {(A−B) ÷ A} × 100
A: Measurement value of optical profile meter of replica before application B: Measurement value of optical profile meter of replica on day 45 or 90 of application

  As is apparent from Table 2, the wrinkle reduction rate of the control application group increased only slightly on the 45th and 90th day of application, whereas the test sample application group applied in all cases. The reduction rate of wrinkles increased significantly compared to before, and became more remarkable on the 90th day after application. When compared between the groups to which the test sample was applied, the wrinkle reduction rate of the group to which test sample 4 or 5 (contained equimolar amounts of glycosylated naringin and glycosylated hesperidin or glycosylated rutin) was the highest. In addition, no subject complained of problems such as skin discomfort, redness, and irritation during and after the test period. This result shows that the skin external preparation containing sugar transfer vitamin P is safe and has an effect of suppressing the formation of wrinkles on the skin and an effect of improving wrinkles. In addition, the effect indicates that when glycosylated vitamin P is used alone, glycosylated naringin is the strongest, and is further enhanced by blending two or more glycosylated vitamin P.

<Experiment 3: Effect of Glucose Transfer Vitamin P Concentration on Wrinkle Formation>
In Experiment 2, since glycosylated vitamin P was found to suppress wrinkle formation and improve wrinkles, a test for examining the effect of the concentration of glycosylated vitamin P on wrinkles was conducted as follows. That is, as a glycosylated vitamin P, a glycosylated vitamin P combination cream (test samples 1 to 8) and a cream not containing a glycosylated naringin (control) were prepared using the glycosylated naringin as shown in Table 3. . 135 volunteer women (35 to 55 years old) were randomly divided into 9 groups of 15 subjects as subjects, and any of the test samples or controls were assigned to 15 subjects in each group as in Experiment 2. 2 times in the morning and evening, each day for 90 days. Before application, on the 45th and 90th day of application, place a circular cup on the site specified from the position of the corner of the eye and the ear, apply medical silicon, and prepare a skin replica with a diameter of 20 mm. did. Wrinkle reduction ratio (%) of the test sample or control of each subject was measured with an optical profilometer in the same manner as in Experiment 2 to measure the degree of wrinkle unevenness of the replica on the 45th day and 90th day of application before application. Is calculated and shown in Table 3. The subjects were instructed not to expose their face excessively to direct sunlight from 4 days before the start of the test to the end of the test.

  As is apparent from Table 3, when applying a cream containing 0.0001% of glycosylated naringin with respect to the total mass of the cream, no difference was observed in the wrinkle reduction rate compared to the case of applying the control. . On the other hand, when a cream containing 0.001% or more of glycosylated naringin with respect to the total mass of the cream is applied, the wrinkle reduction rate is dependent on the concentration as compared with the case of applying the control. It increased significantly, and the effect became remarkable when 0.1% or more was blended. When the blending amount exceeded 5%, no great difference was observed in the wrinkle reduction rate. In addition, when 15% glycerinated naringin was blended, the cream coloration (yellow) with glycerinated naringin became prominent. In addition, no subject complained of problems such as skin discomfort, redness, and irritation during and after the test period. This result shows that the composition for external use containing vitamin P in an amount of 0.001% or more, preferably 0.1% or more, particularly preferably 0.1 to 10% based on the total mass is safe and effective. It shows that wrinkles can be reduced or prevented.

<Experiment 4: Effect of Glucose Transfer Vitamin P on Slimming Effect>
The test which investigates the influence which the glycosylated vitamin P which is an active ingredient of the elastase activity inhibitor of this invention has on slimming was conducted as follows. That is, using the glycosylated vitamin P used in Experiment 1, based on the formulation shown in Table 4, A and B components were individually mixed and dissolved by a conventional method, and the mixed B component was mixed and A Test gels (Test Samples 1 to 3 and Control) were prepared by adding to the ingredients and stirring. In addition, the compounding quantity of vitamin P was mix | blended so that it might become about equimolar with each test sample. Eighty volunteer women (25 to 55 years old) were randomly divided into four groups of 20 as test subjects, and 20 subjects in each of the 3 groups were given one of the test samples, and the remaining 20 people in 1 group. The control gel was applied to the abdomen and thigh of the subject twice a day for 3 weeks. Table 4 also shows the number of subjects who answered “effective” by confirming whether or not the tightening effect (slimming effect) of the abdomen and thigh applied with the gel was recognized.

  As is clear from Table 4, the number of subjects who answered that there was a tightening effect on the abdomen and thigh by applying the test sample was when the gel (control) containing no sugar transfer vitamin P was used. When 3 gels were used, a gel containing sugar transfer vitamin P was used, resulting in 11 to 17 people. In addition, among the three types of test samples, there were many subjects who answered that the gel containing sugar-transferred naringin (test sample 1) or sugar-transferred hesperidin (test sample 2) was effective. In addition, no problems were observed with respect to the feeling of use when the test samples 1 to 3 were used, and the discomfort, redness, and irritation of the skin during and after the test period. This result shows that the composition containing the glycosylated vitamin P has an excellent slimming effect locally, and in terms of the effect, the glycosylated naringin and the glycosylated hesperidin are strong. Moreover, the composition which mix | blended these sugar-transfer vitamin P has told that it is excellent also in safety | security.

<Experiment 5: Effect of glycosylated vitamin P on blood circulation>
A test for examining the effect of the elastase activity inhibitor of the present invention on blood circulation was performed as follows. That is, using the glycosylated vitamin P used in Experiment 1, based on the formulation shown in Table 5, the A component is mixed by a conventional method, heated to 80 ° C. to be uniform, and the B component is mixed therewith Then, 80 ° C. was added and emulsified, and cooled to room temperature with stirring to prepare an O / W emulsified moisturizing cream (test samples 1 to 3 and a control). In addition, the compounding quantity of vitamin P was mix | blended so that it might become equimolar with each test sample. 80 volunteers (40 men and women aged 20 to 40 years old) were randomly divided into 4 groups of 20 (10 men and women each) as subjects, and 20 subjects in each group of 3 groups by simple blind method. For each of the test samples 1 to 3, and for the remaining 20 subjects in each group, a control cream was applied to the back of the right hand of the subject twice a day for about 0.2 g for 4 weeks. The cream was not applied to the back of the left hand. Before the start of application of the cream and after continuous use of any cream for 4 weeks, the subject was allowed to rest for 20 minutes in a constant temperature and humidity room (room temperature 25 ± 1 ° C., relative humidity 55 ± 2%). Thereafter, thermal images of the left and right hand back sides were taken with a thermography measuring instrument (trade name “Thermo Tracer TH 5104”, sold by NEC Sanei Co., Ltd.).

  After the above measurement, the average skin surface temperatures of the backs of the left and right hands were calculated from the obtained thermal images. The difference between the average skin surface temperature of the back of the left and right hands is obtained for each subject, and the average skin temperature difference between the back of the left and right hands is obtained before and after using the cream for each subject before and after applying the cream for 4 weeks. It was. The skin surface temperature difference before use was determined by subtracting the average skin surface temperature (° C.) of the back of the left hand from the average skin surface temperature of the back of the subject's right hand before applying the cream. In addition, after use, the average skin surface temperature (° C.) of the back of the subject's right hand after application of any one of the test samples 1 to 3 or the control cream for 4 weeks is the average of the back of the left hand without application of the cream. The skin surface temperature (° C.) is obtained by subtraction, and the average value of each test sample or control application group is calculated and shown in Table 5.

  As is apparent from Table 5, in any group, no difference was observed in the skin surface temperature difference between the left and right hand backs (skin surface temperature difference before use) before applying the cream. In addition, in the group where the control was applied for 4 weeks, there was almost no difference from the case where the cream was not applied, whereas the cream (test samples 1 to 3) containing sugar transfer vitamin P was applied for 4 weeks. The average skin surface temperature of the back of the right hand to which the cream was applied increased by an average of 1.2 ° C. or more compared to the back of the left hand to which the cream was not applied. Furthermore, among the test samples, the average skin surface temperature difference between the backs of the left and right hands was particularly prominent in the cream formulated with glycosylated naringin (test sample 1) or glycosylated hesperidin (test sample 2). In addition, no subject complained of problems such as skin discomfort, redness, and irritation during and after the test period. This result shows that glycosylated vitamin P has an excellent blood circulation promoting action, and from the viewpoint of the strength of action, metastased naringin and glycosylated hesperidin are excellent. In addition, the topical skin preparation containing these sugar transfer vitamin Ps is excellent in safety.

<Experiment 6: Effect of glycosylated vitamin P on lipase activity>
An experiment to examine the effect of glycosylated vitamin P on lipase activity was performed as follows. That is, the test sample was prepared by diluting the glycosylated vitamin P used in Experiment 1 so as to have the concentrations shown in Table 6. Mcllvaine buffer (pH 7.4, 9.15% 0.1 M citric acid and 90 M 0.2M Na ₂ HPO ₄ containing 25 μl of any of these test samples and 0.1 M 4-methylbelliferylate as a substrate. (Contained at a rate of 85%) was mixed with 50 μl, and 25 μl of 1 unit / ml lipase-containing Mclvaine buffer was added and stirred, followed by reaction at 37 ° C. for 20 minutes. Thereafter, fluorescence intensity (Ex 355 nm, Em 460 nm) was measured with a fluorescent microplate reader: Fluoroscan II (BIO-TEK INSTRUMENT) as an indicator of the amount of 4-methylbelliferon produced as a degradation product of the enzymatic reaction of lipase. Based on this measured value, the results of determining the inhibition rate (%) of lipase activity according to the following formula are shown together in Table 6. Furthermore, the concentration of glycosylated vitamin P necessary for suppressing the used lipase activity by 50% is calculated and shown in Table 6 together.
<Inhibition rate of lipase activity (%)>
Inhibition rate (%) = 100 − [{(A−B) ÷ (C−B)} × 100]
A: Fluorescence intensity when the test sample is added B: Fluorescence intensity of only the Mclvaine buffer C: Fluorescence intensity when the test sample is not added

  As is apparent from Table 6, glycosylated vitamin P showed a concentration-dependent lipase activity inhibitory action. Moreover, when the concentration which suppresses the used lipase activity by 50% is compared between the glycosylated vitamin P used in the test, it was found that glycosylated naringin has the strongest lipase activity inhibiting action. Since lipase is considered to be the cause of acne generation (see, for example, JP-A-2004-43373), this result shows that glycosylated vitamin P has an excellent anti-acne action, and especially glycosylated naringin is particularly strong , Tells that it has anti-acne action.

<Experiment 7: Effect of glycosylated vitamin P on 1-diphenyl-2-picryl hydrazyl radical>
An experiment for examining the effect of glycosylated vitamin P on the 1-diphenyl-2-picryl hydrazyl (hereinafter abbreviated as “DPPH”) radical was performed as follows. That is, the glycosylated vitamin P powder used in Experiment 1 was dissolved in 5 mM acetate buffer (pH 5.5) and serially diluted 3-fold with the same buffer to prepare test samples having the concentrations shown in Table 7. . 50 μl of any of these test samples was mixed with 100 μl of 1 mM DPPH ethanol solution, stirred, reacted at room temperature for 20 minutes, and absorbance at 515 nm using a microplate reader (BIO-TEK INSTRUMENT, model number “EL-340”). Was measured. Based on this measured value, the DPPH radical removal rate (%) is calculated from the following formula and shown in Table 7. The concentration at which 50% of the used DPPH radical is removed is calculated and shown in Table 7.
<Calculation method of DPPH radical removal rate (%)>
DPPH radical removal rate (%) = 100 − [{(A−B) ÷ (C−B)} × 100]
A: Fluorescence intensity when test sample is added B: Fluorescence intensity of acetate buffer only C: Fluorescence intensity when test sample is not added

  As is clear from Table 7, the sugar-transfer vitamin P exhibited a concentration-dependent DPPH radical scavenging activity. In addition, when the concentration of glycosylated vitamin P necessary to remove 50% of DPPH radicals was compared, 3.52 mg / ml and 1.03 mg / ml were respectively obtained for glycosylated naringin, glycosylated hesperidin, and glycosylated rutin. Calculated to be 0.44 mg / ml, and it was found that sugar-transferred rutin removes DPPH radicals most strongly. This result shows that the glycosylated vitamin P has an effect of removing radicals and is therefore excellent in preventing or suppressing skin aging. It also shows that transglycosyl hesperidin and transglycosyl rutin are superior in terms of the strength of radical removal effect.

<Experiment 8: Effect of Glucose Transfer Vitamin P on Nitric Oxide Production>
An experiment for examining the effect of glycosylated vitamin P on the production of nitric oxide (hereinafter abbreviated as “NO”), which is known to induce inflammation, was performed as follows. That is, a mouse macrophage cell line (RAW264.7 cell) was suspended in Dulbecco's MEM medium (D-MEM), seeded in a 96-well microplate, and LPS was added to the medium to 8 μg / ml. The final cell volume was 5 × 10 ⁴ cells / 200 μl / well. Glucose transfer vitamin P powder used in Experiment 1 was diluted with Dulbecco's phosphate buffer (D-PBS) and seeded with RAW264.7 cells. The test sample prepared as described above was added and cultured for 48 hours. The amount of NO in the culture supernatant was measured (Griess method). Based on this measured value, the NO production inhibition rate (%) was determined by the following calculation method and shown in Table 8. Moreover, the concentration of glycosylated vitamin P that suppresses NO production by 50% is calculated and shown together in Table 8. As a positive control, dipotassium glycyrrhizinate, which is known to have an anti-inflammatory effect, was similarly diluted and used.
<Calculation method of NO production inhibition rate (%)>
NO production inhibition rate (%) = 100 − [{(A−B) ÷ B} × 100]
A: NO amount when test sample is added B: NO amount when only D-PBS is added

  As is apparent from Table 8, the sugar transfer vitamin P and dipotassium glycyrrhizinate showed concentration-dependent NO production inhibitory activity. In addition, when the concentration required to suppress NO production by 50% in the experimental system was compared, dipotassium glycyrrhizinate (positive control), glycosylated naringin, glycosylated hesperidin and glycosylated rutin were each 0.47 mg / Calculated as ml, 0.56 mg / ml, 1.23 mg / ml and 1.76 mg / ml. This result indicates that glycosylated vitamin P is excellent in anti-inflammatory effect because it is excellent in the action of suppressing NO production. In terms of the NO production inhibitory action, the anti-inflammatory effect is the best among the glycosylated vitamin Ps. Glycosylated naringin is the best, and it has almost the same anti-inflammatory effect as dipotassium glycyrrhizinate used as a positive control. It tells you what you are doing.

<Experiment 9: Effect of Glucose Transfer Vitamin P on Blotches and Freckles>
It is known that transglycosyl hesperidin has a whitening effect. Moreover, since the anti-inflammatory action was found in the glycosylated naringin in the same manner as the glycosylated hesperidin in the experiment 8, a test for confirming that the glycosylated naringin also had a whitening effect was performed as follows. That is, a sugar-transfer vitamin P combination cream (test samples 1 to 3) and a cream not containing sugar transfer vitamin P (control) were prepared according to the formulation shown in Table 9. 60 volunteer women (29 to 58 years old) were randomly divided into 4 groups of 15 subjects, and 15 subjects in each of the 3 groups were given one of the test samples and the remaining 15 in 1 group. The control cream was evenly applied to the face twice daily for 180 days each day. Before the application, on the 90th day of application and on the 180th day of application, a questionnaire was conducted, and the results are also shown in Table 9. In addition, the state of the stain / freckle is visually and photographally evaluated in four stages, markedly improved (◎), improved (◯), unchanged (Δ), and increased (×) compared to before application. The evaluation with the largest number of people in each group was taken as the evaluation of the effect of the test sample or control on the stain / freckle. As a result, in any group, 11 or more out of 15 persons had the same evaluation. The subjects were instructed not to expose their face excessively to direct sunlight from 4 days before the start of the test to the end of the test.

  As is clear from Table 9, in the control application group, no change was observed in the spots and freckles compared to before application. On the other hand, when a test sample containing glycosylated vitamin P was applied, in all cases, from the 90th day of application, improvement in spots and freckles was observed compared to before application, and glycosylated naringin In the cream containing (Test sample 1) and sugar-transferred hesperidin (Test sample 2), the effect was remarkable on the 180th day after application. In addition, no subject complained of problems such as skin discomfort, redness, and irritation during and after the test period. This result shows that the external preparation for skin containing sugar transfer vitamin P is safe and has an excellent whitening effect on the skin. Moreover, the improvement effect tells that transglycerin naringin and transglycosyl hesperidin are strong.

<Experiment 10: Effect of glycosylated vitamin P on lipid peroxide and in vivo ascorbic acid>
In Experiment 4, 6 or 7, it was confirmed that glycosylated vitamin P had an effect on lipid metabolism and radicals in the living body. Experiments were conducted as follows to examine the effects of glycosylated vitamin P on lipid peroxide and in vivo ascorbic acid involved in the elimination of lipid peroxide. That is, 60 volunteers (29 to 58 years old, cholesterol level 200 to 280 mg / dl) determined to have a relatively high blood cholesterol level in the health check were randomly divided into 4 groups of 15 subjects each as subjects. The 15 subjects in each of the 3 groups were orally ingested once a day for 25 weeks, with 0.5 g of the sugar-transfer vitamin P powder used in Experiment 1 as a test sample. The remaining 15 people in 1 group did not take sugar transfer vitamin P as a control. There were no dietary restrictions during the study period. Blood was collected at 12 weeks and 25 weeks after ingestion, and the amount of lipid peroxide in the serum was measured using a commercially available lipid peroxide measurement kit (available from Cayman CHEMIKAL). The measurement of blood ascorbic acid level was requested from a clinical testing company. Based on the measurement results, for each group, the average amount of lipid peroxide and ascorbic acid in serum was calculated, and the lipid peroxide reduction rate (%) and ascorbic acid reduction inhibition rate (% ) Is shown in Table 10.
<Calculation method of lipid peroxide inhibition rate (%)>
Lipid peroxide reduction rate (%) = 100 − {(A ÷ B) × 100}
A: Amount of lipid peroxide in the blood when the test sample is ingested B: Amount of lipid peroxide in the blood when the sample is not ingested <Calculation method for the inhibition rate (%) of ascorbic acid reduction>
Ascorbic acid reduction inhibition rate (%) = {(A ÷ B) × 100} −100
A: Blood ascorbic acid level when the test sample is ingested B: Blood ascorbic acid amount when the test sample is not ingested

  As is apparent from Table 10, when glucose-transferred vitamin P was ingested, the lipid peroxide reduction rate in blood increased with time compared to the case of no intake. Moreover, the ascorbic acid reduction inhibitory rate in blood also increased over time compared with the case of no intake. In addition, no subjects complained of problems such as discomfort, redness, irritation, diarrhea, fever, nausea / vomiting during and after the study. In terms of the strength of these effects, glycosylated naringin and glycosylated hesperidin are particularly excellent. This result indicates that by taking sugar-transferred vitamin P orally, not only the lipid peroxide in the body can be effectively reduced, but also the reduction of in vivo ascorbic acid accompanying stress and the like can be suppressed. .

<Experiment 11: Effect of Concomitant Use of Sugar Transfer Vitamin P and Other Components on Wrinkle Formation>
In Experiment 2, since the strong wrinkle improving effect was observed in the glycosylated vitamin P, a test for examining the effect of the combined use of the glycosylated vitamin P and other components on wrinkles was conducted as follows. That is, the cream which mix | blended the sugar transfer naringin as vitamin P like the mixing | blending prescription shown in Table 11 (test sample 1). Indigo water extract with transglycosylated naringin (trade name “Indigo Luros” sold by Hayashibara Biochemical Laboratories, Inc., a water extract of indigo grass containing 30% 1,3-butylene glycol, solid content derived from indigo grass) ), Cyclonigerosyl nigerose (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.), L-ascorbic acid-2-glucoside (sold by Hayashibara Biochemical Laboratories Co., Ltd., trade name “AA2G”) or photosensitivity Cream containing any of Moto 101 No. 101 (available from Hayashibara Biochemical Laboratories Co., Ltd.) (test sample 2, test sample 4, test sample 6, test sample 8 respectively) Cream blended with any one of extract, cyclonigerosyl nigerose, L-ascorbic acid-2-glucoside or photosensitizer 101 (test sample 3, test sample 5, test sample 7, test Fee 9), and, glycosyltransferases naringin also indigo grass extract, cycloalkyl Escape sill nigero scan, do not contain any of the L- ascorbic acid 2-glucoside or photosensitizer No. 101 cream (control) was prepared. 100 volunteer women (34 to 58 years old) were randomly divided into 10 groups of 10 as subjects, and 10 subjects in each of 9 groups were assigned one of the test samples to the remaining 10 groups. The control cream was applied evenly to the face twice a day for 90 days every day. Before application, on the 45th and 90th day of application, place a circular cup on the site specified from the position of the corner of the eye and the ear, apply medical silicon, and prepare a skin replica with a diameter of 20 mm. did. Wrinkle reduction rate calculated by the same calculation method as in Experiment 2 by measuring the degree of unevenness of the replica of the test sample or control of each subject before application, 45 days of application and 90 days of application with an optical profilometer ( %) Is also shown in Table 11. The subjects were instructed not to expose their face excessively to direct sunlight from 4 days before the start of the test to the end of the test.

  As is apparent from Table 11, the wrinkle reduction rate of the control application group was only slightly increased on the 45th and 90th day of application, whereas the test sample (test sample) containing only glycosylated naringin was used. 1) Test sample (test sample 2, test sample 4, test sample blended with either cyanobacteria extract, cyclonigerosyl nigerose, L-ascorbic acid-2-glucoside or photosensitizer 101 together with transglycated naringin In each of the test sample 6 and the test sample 8) application group, the wrinkle reduction rate was significantly increased as compared with that before application, and became more prominent on the 90th day after application. Moreover, the test sample (Test sample 3, Test sample 5, which does not contain transglycerin naringin, and mix | blends any of cyanobacteria water extract, cyclonigerosyl nigerose, L-ascorbic acid-2-glucoside, or photosensitizer 101) In each of the test sample 7 and the test sample 9) application group, the wrinkle reduction rate was significantly higher than that before the application except for the test sample (test sample 5) application group containing cyclonigerosyl nigerose. It rose and became more prominent on the 90th day after application. When compared between the groups in which significant wrinkle improvement was observed as compared with the control, Ginseng water extract, cyclonigerosyl nigerose, L-ascorbic acid-2-glucoside, or photosensitizer 101 was used together with transglycerin naringin. The effect is remarkably recognized in the test sample (test sample 2, test sample 4, test sample 6 and test sample 8) applied with any of these, and among them, indigo water extract or L- The increase in the wrinkle reduction rate of the test sample (test sample 2 and test sample 6) coated with ascorbic acid-2-glucoside was particularly remarkable. In addition, no subject complained of problems such as skin discomfort, redness, and irritation during and after the test period. This result shows that the wrinkle reduction effect by glycosylated vitamin P is enhanced by the combined use of cyanobacteria extract, cyclonigerosyl nigerose, L-ascorbic acid-2-glucoside or photosensitizer 101, and the enhancement effect is It shows that it is particularly effective when used in combination with a cyanobacteria extract and / or L-ascorbic acid-2-glucoside.

  The results of Experiments 1 to 11 show that vitamin P has a slimming effect, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, and in vivo ascorbine in addition to the elastase activity inhibitory action. Since it has various actions such as acid reduction suppression, an elastase activity inhibitor containing one or more vitamin P as an active ingredient has an anti-wrinkle effect and does not dull the skin color of the face, etc. In addition to improving the above, it is possible to suppress the occurrence of spots and freckles associated with sunburn, etc., indicating that it is effective in preventing skin aging. Moreover, from the point of an effect, the thing which mix | blended the sugar transfer vitamin P as an active ingredient is told that it is desirable. Moreover, in the test with volunteers as subjects, in either case, there was no subject complaining of problems such as uncomfortable feeling, redness, irritation, etc. during the test period and after completion of the test. An elastase activity inhibitor for ingestion shows excellent safety.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated further in detail, the technical scope of this invention should not be construed restrictively by these Examples at all.

<Elastase activity inhibitor>
Based on the following formulation, a liquid elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Glycerin 5
1,3-butylene glycol 6.5
Polyoxyethylene (20E.O.) sorbitan monolaurate 1.2
Ethyl alcohol 8
Carbohydrates containing carbohydrate derivatives of α, α-trehalose (sales by Hayashibara Biochemicals, Inc., trade name “Tornale”,
About 60 glycosyl trehalose based on α-maltosyl α, α-trehalose in terms of anhydride
% And about 40% hydrogenated water tank) 5
Aika grass water extract (sales of Hayashibara Biochemicals, Inc., trade name “Ai Roulos”, Aika grass water extract containing 30% 1,3-butylene glycol) 1
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
(Purity of glucosylnarindin 65%) 1
Citric acid 0.1
Sodium citrate 0.3
P-methoxycinnamic acid-2-ethylhexyl 0.1
Hyaluronic acid (average molecular weight about 10,000) 0.1
Photosensitive Element 201 0.002
Perfume Appropriate amount of purified water Remaining amount

  This product has excellent anti-wrinkle effect, slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammation, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression and / or anti-aging makeup It is also useful as a skin external preparation in the form of water.

<Elastase activity inhibitor>
Of the prescription in Example 1, 1% sugar-transferred naringin, 1% sugar-transferred hesperidin (sales by Hayashibara Biochemicals Co., Ltd., trade name “alpha glucosyl hesperidin”), sugar transfer rutin (Hayashibara Biochemical Laboratories) Example 1 except that sales and trade name "alpha glucosyl rutin") 1% or sugar transfer esculin (manufactured by Hayashibara Biochemical Laboratories, Inc., containing about 60% glycosyl esculin in terms of anhydride) 1% A liquid elastase activity inhibitor was prepared with the same formulation.

  This product has excellent anti-wrinkle effect, slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammation, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression and / or anti-aging makeup It is also useful as a skin external preparation in the form of water.

<Elastase activity inhibitor>
Based on the following formulation, an emulsion of an elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Polyoxyethylene (20E.O.) polyoxypropylene (2E.O.) cetyl alcohol 1
Silicon KF96 (20cs) (Shin-Etsu Chemical Co., Ltd. sales) 2
Liquid paraffin (medium viscosity) 3
1,3-butylene glycol 5
4-n-butylresorcinol 0.3
Glycerin 2
Ethyl alcohol 15
Carboxyvinyl polymer 0.3
Hydroxypropyl cellulose 0.1
2-Aminomethylpropanol 0.1
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
(Purity of glucosylnardin) 96%) 0.5
L-ascorbic acid-2-glucoside (Hayashibara Biochemical Laboratories, Inc., trade name "AA2G") 1
Photosensitive Element 101 0.005
Preservative Appropriate amount pH adjuster Appropriate amount of purified water is added to make the total amount 100%.

  This product has an excellent anti-wrinkle effect, and is an emulsion for slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammation, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression and / or anti-aging. It is also useful as a skin external preparation. In addition, this product is excellent in skin permeability and spreadability.

<Elastase activity inhibitor>
Of the prescription in Example 3, 0.5% sugar-transferred naringin, 0.5% sugar-transferred hesperidin (trade name “alpha glucosyl hesperidin” sold by Hayashibara Biochemical Laboratories Co., Ltd.), sugar transfer rutin (Hayashibara Co., Ltd.) Biochemical Laboratories, trade name "alpha glucosyl rutin") 0.5% or sugar transfer esculin (manufactured by Hayashibara Biochemical Laboratories, Inc., containing about 60% glycosyl esculin in terms of anhydride) Except having changed, the emulsion elastase activity inhibitor was prepared by the same formulation as Example 3.

  In addition to anti-wrinkle effect, this product is an emulsion for slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression and / or anti-aging It is also useful as a skin external preparation. In addition, this product is excellent in skin permeability and spreadability.

<Elastase activity inhibitor>
Based on the following formulation, an emulsion of an elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Ethyl alcohol 15
Polyoxyethylene (20E.O.) polyoxypropylene (2E.O.) cetyl alcohol 1
Silicon KF96 (20cs) (Shin-Etsu Chemical Co., Ltd. sales) 2
Liquid paraffin (medium viscosity) 3
1,3-butylene glycol 5
L-ascorbic acid-2-glucoside 2
Glycerin 2
Carbohydrates containing carbohydrate derivatives of α, α-trehalose (sales by Hayashibara Biochemicals, Inc., trade name “Tornale”) 1
Carboxyvinyl polymer 0.3
Hydroxypropyl cellulose 0.1
2-Aminomethylpropanol 0.1
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
1.5% purity of glucosylnarindin) 1.5
Glucose transfer esculin (manufactured by Hayashibara Biochemical Research Institute,
Glycosyl esculin purity 60%) 0.5
Sodium hyaluronate 0.02
Photosensitive Element 101 0.005
Preservative Add an appropriate amount of purified water to make the total amount 100%.

  This product has an excellent anti-wrinkle effect, and is an emulsion for slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammation, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression and / or anti-aging. It is also useful as a skin external preparation. In addition, this product is excellent in skin permeability and spreadability.

<Elastase activity inhibitor>
Of the formulation of Example 5, 2% sugar-transferred naringin, 2% sugar-transferred hesperidin (trade name “alpha glucosyl hesperidin” sold by Hayashibara Biochemical Laboratories, Inc.) or sugar transfer rutin (Hayashibara Biochemical Laboratories, Inc.) Emulsion elastase activity inhibitor was prepared in the same formulation as in Example 5 except that the product was changed to 2% (trade name, “alpha glucosyl rutin”).

  This product has an excellent anti-wrinkle effect, and is an emulsion for slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammation, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression and / or anti-aging. It is also useful as a skin external preparation. In addition, this product is excellent in skin permeability and spreadability.

<Elastase activity inhibitor>
Based on the following formulation, a liquid elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Photosensitive Element 301 0.005
Glycerin 2
Water-containing crystal α, α-trehalose 0.03
Glucose transfer hesperidin (Hayashibara Biochemical Laboratories, Inc.,
Product name "Alpha Glucosyl Hesperidin") 0.001
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
(Purity of glucosylnarindin 65%) 0.001
Glucose transfer rutin (Hayashibara Biochemical Research Institute sales,
Product name "alpha glucosyl rutin") 0.001
Indigo grass water extract (Hayashibara Biochemical Research Institute sales,
Product name “Ai Luros”, water extract of indigo grass containing 30% 1,3-butyrene recall) 0.5
Seaweed extract 0.1
Button extract 0.1
Assembly extract 0.1
Ethanol 43
Add purified water to bring the total volume to 100%.
This product has an excellent hair growth effect, promotes hair growth, increases hair density, and gives tension to the hair. In addition, this product has anti-scaling and anti-aging effects on the scalp, and has strong antibacterial properties, so it can be used as a hair tonic form of a topical skin preparation that suppresses dandruff, itching and hair loss and keeps the scalp clean. Useful. In addition, when this product is used on a scalp in which the hair root is implanted, it promotes the proliferation of dermal papilla cells, promotes blood circulation of the scalp, and has an excellent effect in improving the rate of growth of the implanted hair root on the scalp.

<Elastase activity inhibitor>
Based on the following formulation, a creamy elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Polyglyceryl myristate-10 3
Glycosylnarindin (produced by Hayashibara Biochemical Laboratories Co., Ltd.) 0.05
Glucose transfer rutin (Hayashibara Biochemical Research Institute sales,
Product name "alpha glucosyl rutin") 0.05
Glucose transfer hesperidin (Hayashibara Biochemical Laboratories, Inc.,
Product name "Alpha Glucosyl Hesperidin") 0.01
Lanolin 0.5
Octyldodecanol 2
Cetyl octanoate 3
Squalane 5
Dimethicone 0.3
Behenyl alcohol 3
Cetyl alcohol 2
Batyl alcohol 1
Cetyl palmitate 1.5
Glyceryl stearate 2.3
Hydrogenated lecithin 0.1
Butylene glycol 5
Pentylene glycol 3.5
Ceramide 0.5
Stearic acid 0.5
Glycerin 5
Carbohydrates containing carbohydrate derivatives of α, α-trehalose (sales by Hayashibara Biochemicals, Inc., trade name “Tornale”) 2
α, α-trehalose (Hayashibara Biochemical Laboratories Co., Ltd., for cosmetics) 0.05
L-ascorbic acid-2-glucoside 2
Indigo grass water extract (Hayashibara Biochemical Research Institute sales,
Product name “Ai Luros”, water extract of indigo grass containing 30% 1,3-butylene recall) 1
Pullulan 0.1
Grapefruit peel oil 0.001
Lavender oil 0.001
Pomegranate extract 0.001
Oat extract 0.001
Edelweiss extract 0.001
Hydrolyzed collagen 0.001
Photosensitive element 201 0.001
Sodium hyaluronate 0.001
Hydrolyzed hyaluronic acid (average molecular weight about 10,000) 0.002
Arbutin 0.005
Tocopherol 0.005
Ubiquinone 0.001
Xanthan gum 0.001
Carbomer 0.001
Potassium hydroxide An appropriate amount of purified water is added to make the total amount 100%.

  This product has excellent anti-wrinkle effect, slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression and / or anti-aging cream It is also useful as a skin external preparation. In addition, this product is excellent in skin permeability and spreadability.

<Elastase activity inhibitor>
Based on the following formulation, a soft solid elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Purified water 1.5
Glycerin 0.2
Pullulan 0.5
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
0.1% purity of glucosylnarindin) 0.1
Glucose-transferred hesperidin (sales by Hayashibara Biochemical Co., Ltd., trade name, “alpha-glucosyl hesperidin”) 0.1
Macadamia nut oil fatty acid cholesteryl 3
POE (25) POP (20) 2-tetradecyl ether 1
Squalane 10
Carnavalou 2
Candelilla Row 8
Ceresin 14
Isostearic acid diglyceride 33
Cyclonigerosyl nigerose (produced by Hayashibara Biochemical Laboratories Co., Ltd.) 2
Castor oil 17.2
Titanium dioxide 4.5
Red No. 201 1
Red No. 202 2

  This product has excellent anti-wrinkle effect, slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression and / or aging prevention lipstick It is also useful as a skin external preparation. Moreover, this product is excellent in permeability and spreadability in the lips.

<Elastase activity inhibitor>
Based on the following formulation, a soft solid elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Purified water 1.5
Edetate trisodium 0.01
Glycerin 0.2
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
0.1% purity of glucosylnarindin) 0.1
Glucose transfer rutin (Hayashibara Biochemical Research Institute sales,
Product name "alpha glucosyl rutin") 0.7
Macadamia nut oil fatty acid cholesteryl 3
Dimethicone polyol 0.5
Methylphenylpolysiloxane 10
Microcrystalline wax 1
Ceresin 14
Glyceryl triisooctanoate 35
Hydrogenated polybutene 10
Octyl methoxycinnamate 5
Dibutylhydroxytoluene 0.1
Tocopherol acetate 0.1
Trioctyl trioctanoate proper amount Photosensitive element 101 0.005
Bengala 2
Titanium dioxide 4

  This product has excellent anti-wrinkle effect, slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression and / or aging prevention lipstick It is also useful as a skin external preparation. Moreover, this product is excellent in permeability and spreadability in the lips.

<Elastase activity inhibitor>
Based on the following formulation, a liquid elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Piroctone Olamine 0.5
β-glycyrrhetinic acid 0.02
Edetate disodium 0.3
Photosensitive Element 201 0.002
Citric acid 0.3
N-coconut oil fatty acid acyl-DL-alanine triethanolamine solution 20
N-coconut oil fatty acid acyl-DL-glutamic acid triethanolamine solution 2
Palm oil fatty acid amidopropyl betaine solution 15
Lauryldimethylaminoacetic acid betaine 3
Ethanolamide with coconut oil fatty acid 2
Poly (dimethylmethylenepiperidinium chloride) solution 0.2
Indigo grass water extract (Hayashibara Biochemical Research Institute sales,
Product name “Ai Luros”, water extract of indigo grass containing 30% 1,3-butyrene recall) 0.1
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
(Purity of glucosylnardin) 65%) 0.5
Glucose transfer hesperidin (Hayashibara Biochemical Laboratories, Inc.,
Product name "Alpha Glucosyl Hesperidin") 0.5
Carbohydrates containing carbohydrate derivatives of α, α-trehalose (sales by Hayashibara Biochemicals, Inc., trade name “Tornale”) 1
Assembly extract 0.02
Phenoxyethanol 0.5
Pullulan 0.001
Fragrance 0.2
Photosensitive Element 101 0.005
Add purified water to bring the total volume to 100%.
This product has anti-scaling and anti-aging effects on the scalp and has strong antibacterial properties. is there.

<Elastase activity inhibitor>
Based on the following formulation, a liquid elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Piroctone Olamine 0.2
Edetate disodium 0.3
Stearyl glycyrrhetinate 0.05
Photosensitive Element 201 0.002
Photosensitive element 301 0.001
Citric acid 0.3
Assembly extract 0.02
1,3-butylene glycol 3
Stearic acid dimethylaminopropylamide 1
O- [2-hydroxy-3- (trimethylammonio) chloride
Propyl] hydroxyethyl cellulose 0.5
Hardened oil 4
Concentrated glycerin 3
Vaseline 5
Jojoba oil 0.1
Isopropyl palmitate 1.5
Aminoethylaminopropylsiloxane / dimethylsiloxane copolymer emulsion 1
Isopropyl palmitate 1
Hydroxyethyl cellulose 0.5
Pullulan 0.01
Sodium hyaluronate (average molecular weight about 900,000) 0.01
Hyaluronic acid (average molecular weight about 10,000) 0.02
Polyoxyethylene lauryl ether 0.01
Indigo grass water extract (Hayashibara Biochemical Research Institute sales,
Product name “Ai Luros”, water extract of indigo grass containing 30% 1,3-butyrene recall) 0.5
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
(Purity of glucosylnardin) 65%) 0.5
Glucose transfer hesperidin (Hayashibara Biochemical Laboratories, Inc.,
Product name "Alpha Glucosyl Hesperidi 0.5
Carbohydrates containing saccharide derivatives of α, α-trehalose (sales by Hayashibara Biochemicals, Inc., trade name “Tornale”) 1.5
Fragrance 0.2
Photosensitive Element 101 0.005
Add purified water to bring the total volume to 100%.
This product has anti-aging and anti-aging effects on the scalp, has blood circulation promoting action, and has strong antibacterial properties, so it has excellent hair-growth effect, suppresses hair loss, and keeps the scalp clean. It is useful as an external preparation.

<Elastase activity inhibitor>
Based on the following formulation, a solid elastase activity inhibitor was prepared by a conventional method. Specifically, 96.5 parts by mass of neat soap obtained by subjecting beef tallow and coconut oil in a mass ratio of 4: 1 to normal saponification / salting out method to 1 part by mass of extract of green grass water extract, α, α-trehalose Carbohydrate containing saccharide derivatives (sales by Hayashibara Biochemical Research, Inc., trade name “Tornale”) 1.5 parts by mass, L-ascorbic acid 2-glucoside (sales by Hayashibara Biochemistry Labs, trade name “AA2G”) ), 0.5 parts by weight of sucrose, sugar-transferred naringin (produced by Hayashibara Biochemical Laboratories, Inc., α-glycosylnarindine purity 65%), 0.5 parts by weight, sugar-transferred isoquercitrin (manufactured by Hayashibara Biochemical Laboratories, Inc.) , Α-isoquercitrin purity 65%) 0.5 parts by weight, 1 part by weight of maltitol, 0.0001 part by weight of Photosensitive Element 301 and an appropriate amount of fragrance are added and mixed uniformly, then poured into a frame and cooled.・ Solidification It was to prepare a solid of elastase activity inhibitor. This product uses elastase activity inhibition, slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammation, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction by glycosylated naringin and glycosylated isoquercitrin It has excellent effects such as suppression, and it is useful as a soap external preparation in the form of soap with excellent feeling after use without causing skin irritation. In addition, this product is excellent in anti-aging effect.

<Elastase activity inhibitor>
Based on the following formulation, a pasty elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Dicalcium phosphate 45
Pullulan 2.9
Sodium lauryl sulfate 1.5
Glycerin 20
Polyoxyethylene sorbitan laurate 0.5
Sorbitol 10
Maltitol 6
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
(Purity of glucosylnardin) 65%) 0.5
Indigo grass water extract (Hayashibara Biochemical Research Institute sales,
No 1,3-butylene glycol) 1
Tetrahydrocurcumin 0.5
Preservative Add an appropriate amount of purified water to make the total amount 100%.

  This product is useful as an external preparation for toothpaste in the form of a toothpaste that promotes gingival blood circulation, maintains gum elasticity and elasticity, has an excellent anti-inflammatory effect, and maintains and enhances oral health.

<Elastase activity inhibitor>
Of the formulation of Example 14, 2% sugar-transferred naringin, 2% sugar-transferred hesperidin (trade name “alpha glucosyl hesperidin” sold by Hayashibara Biochemical Laboratories, Inc.) or sugar transfer rutin (Hayashibara Biochemical Laboratories, Inc.) A pasty elastase activity inhibitor was prepared in the same formulation as in Example 14 except that the product was changed to 2% (trade name, “alpha glucosyl rutin”).

  This product is useful as an external preparation for toothpaste in the form of a toothpaste that promotes gingival blood circulation, maintains gum elasticity and elasticity, has an excellent anti-inflammatory effect, and maintains and enhances oral health.

<Elastase activity inhibitor>
Based on the following formulation, a pasty elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
β-Glycyrrhizic acid 0.05
Cetylpyridium chloride 0.05
Calcium hydrogen phosphate 29
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
0.1% purity of glucosylnarindin) 0.1
Glucose transfer hesperidin (Hayashibara Biochemical Laboratories, Inc.,
Product name "Alpha Glucosyl Hesperidin") 0.9
Concentrated glycerin 20
Carbohydrates containing carbohydrate derivatives of α, α-trehalose (sales by Hayashibara Biochemicals, Inc., trade name “Tornale”) 9
L-ascorbic acid-2-glucoside 1
Silicic anhydride 5
Titanium oxide 2
Sodium lauryl sulfate 1.2
Sodium carboxymethylcellulose 1.2
Polyoxyethylene hydrogenated castor oil 1
Ethanol 0.5
Propolis extract (sales from Hayashibara Biochemical Research Co., Ltd.) 0.5
Magnesium phosphate 0.3
Lauroyl sarcosine sodium 0.2
Maltitol 0.1
Paraoxybenzoic acid ester 0.1
Fragrance Appropriate amount of purified water is added to make the total amount 100%.

  This product contains glycated naringin, so it promotes gingival blood circulation, maintains the gums and elasticity of the gums, has an anti-inflammatory effect, and is useful as a toothpaste-type skin external preparation that maintains and enhances oral health. It is.

<Elastase activity inhibitor>
Based on the following formulation, a gel elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
β-Glycyrrhizic acid 0.05
Cetylpyridium chloride 0.05
Sorbitol solution 30
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
0.1% purity of glucosylnarindin) 0.1
Glucose transfer rutin (Hayashibara Biochemical Research Institute sales,
Product name "αG Rutin") 0.9
Glucose transfer isoquercitrin (manufactured by Hayashibara Biochemical Research Institute, Inc., purity of glucosylisoquercitrin 65%) 0.2
Aizusa water extract (manufactured by Hayashibara Biochemical Research Institute, Inc.
No 1,3-butylene glycol) 20
Concentrated glycerin 10
Carbohydrates containing carbohydrate derivatives of α, α-trehalose (sales by Hayashibara Biochemicals, Inc., trade name “Tornale”) 8
Hydrous silica 9
Silicic anhydride 7
Cyclonigerosyl nigerose (produced by Hayashibara Biochemical Laboratories Co., Ltd.) 2
Xylitol 3
Sodium carboxymethylcellulose 1.2
Polyoxyethylene hydrogenated castor oil 0.5
Ethanol 0.5
Propolis extract (sales of Hayashibara Biochemical Research Co., Ltd.,
Product name “Hayashibara Propolis”) 0.5
Maltitol 0.1
Paraoxybenzoic acid ester 0.1
Fragrance Appropriate amount of purified water is added to make the total amount 100%.

  This product is useful as a toothpaste-type skin external preparation that promotes gingival blood circulation, maintains the gums and elasticity of the gums, has an excellent anti-inflammatory effect, and maintains and enhances oral health.

<Elastase activity inhibitor>
Based on the following formulation, a liquid elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Ethanol 15
Syrup containing carbohydrate derivatives of α, α-trehalose (sales company Hayashibara Corporation, trade name “Hellodex”) 8
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
0.1% purity of glucosylnarindin) 0.1
Glucose transfer hesperidin (Hayashibara Biochemical Laboratories, Inc.,
Product name "Alpha Glucosyl Hesperidin") 0.5
Standard mixture of equimolar mixture of sugar-transferred rutin and isoquercitrin used in Experiment 1 0.5
L-ascorbic acid-2-glucoside 1
Polyoxyethylene hydrogenated castor oil 2
Saccharin sodium 0.02
Sodium benzoate 0.05
Sodium dihydrogen phosphate 0.1
Coloring amount appropriate amount perfume amount appropriate amount water 72.7

  This product is suitable for the improvement of dry mouth due to Sjogren's syndrome, etc., as well as the prevention and treatment of oral inflammation and taste disorders, as well as maintaining the gums and elasticity of the gums. It is useful as a skin external preparation.

<Elastase activity inhibitor>
Based on the following formulation, a pasty elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Sodium acetate 1
Sodium lactate 4
Glycerin 10
Peppermint oil 0.5
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
(Purity of glucosylnardin) 65%) 3
L-ascorbic acid-2-glucoside 2
Vaseline 48
Tree wax 10
Lanolin 10
Sesame oil 10.5
Cyclonigerosyl nigerose (manufactured by Hayashibara Biochemical Research Institute) 1

  This product is excellent in suppressing the generation of wrinkles on the skin, slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction inhibition and / or It is also useful as a skin external preparation in the form of an ointment for preventing aging. In addition, this product has excellent skin permeability and spreadability, and can be used for the purpose of maintaining and improving skin health.

<Elastase activity inhibitor>
Based on the following formulation, a pasty elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Indigo grass water extract (Hayashibara Biochemical Research Institute sales,
No 1,3-butylene glycol) 35
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
0.2% purity of α-glucosylnarindin) 0.2
Photosensitive element 201 (0.1% ethanol solution) 3
Polyethylene glycol 1500 62

  This product is excellent in suppressing the generation of wrinkles on the skin, slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction inhibition and / or It is useful as a skin external preparation in the form of an ointment for preventing aging. In addition, this product has excellent skin permeability and spreadability, and can be used for the purpose of maintaining and improving the health of the skin, as well as for the purpose of dry skin disease, anti-itching, anti-inflammatory, and pressure ulcer (tackiness) improvement. it can.

<Elastase activity inhibitor>
Based on the following formulation, a jelly-like elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Glycerin 15
Ethanol 12
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
7) Purity of glucosylnarindin 65%
Cyclonigerosyl nigerose (Manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) 0.5
Peppermint oil 0.5
Bitter aqueous solution (hardness 54,000 mg / ml) 1.5
Gelling base (Hibiswako 104) 0.65
Polyoxyethylene (20) sorbitan monooriate 0.5
Photosensitive Element 201 0.005
2,2 ′, 2 ″ -nitrilotriethanol 1

  This product has excellent skin wrinkle-suppressing effect, slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction inhibition and / or anti-aging It is also useful as a skin external preparation in the form of a jelly ointment. In addition, this product has excellent skin permeability and spreadability, and can be used for the purpose of maintaining and improving skin health.

<Elastase activity inhibitor>
Based on the following formulation, a powdery elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Hydrous crystal α, α-trehalose (Hayashibara Biochemical Laboratories sales, cosmetics) 70.5
Sodium bicarbonate 12.5
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
7.5% purity of glucosylnarindin) 7.5
Powder containing α, α-trehalose and bitter juice prepared by the method described in Example 9 of WO2003 / 016325 in a mass ratio of 144: 202 5.5
Cyclonigerosyl nigerose (produced by Hayashibara Biochemical Laboratories Co., Ltd.) 2
Photosensitive element 201 0.0015

  This product is excellent in suppressing and improving skin wrinkles, and slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction inhibition and Since it also has effects such as prevention of aging, it is useful as a skin external preparation in the form of a bath preparation that improves skin metabolism and has an excellent anti-aging effect.

<Elastase activity inhibitor>
Based on the following formulation, a film-form elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Pullulan (For Hayashibara Corporation sales, food additive) 22
Carrageenan 1
Xanthan gum 0.15
Locust bean gum 0.15
Maltitol 0.8
Deionized water 69.25
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
1.5% purity of glucosylnarindin) 1.5
Glucose transfer hesperidin (Hayashibara Biochemical Laboratories, Inc.,
Product name "Alpha Glucosyl Hesperidin") 1.5
Emulsified mint oil 2.6
Propolis extract 0.5
Sucralose 0.3
Citric acid 0.25

  Since this product contains glycerinated naringin and glycated hesperidin, it has excellent skin wrinkle-suppressing effects, retains the elasticity and elasticity of the skin and gums, improves skin metabolism, slimming, promotes blood circulation, Excellent lipase activity inhibition, radical removal, anti-inflammatory, whitening, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression, anti-aging, fatigue recovery, stress reduction, sleep quality improvement, etc. It is useful as an oral ingestion in the form of a cool mouth film.

<Elastase activity inhibitor>
Based on the following formulation, an elastase activity inhibitor in the form of chewing gum was prepared by a conventional method.
(Prescription) (%)
Gum base 30
Sucrose 39.7
Hydrous crystals α, α-trehalose (Hayashibara Corporation sales,
Product name “Treha”) 30
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
(Purity of glucosylnardin) 65%) 0.5
Glucose transfer hesperidin (Hayashibara Biochemical Laboratories, Inc.,
Product name "Alpha Glucosyl Hesperidin") 2.5
Fragrance Appropriate amount of pigment Appropriate amount is 100%.

  Since this product contains glycerinated naringin and glycated hesperidin, it has excellent skin wrinkle-suppressing effects, retains the elasticity and elasticity of the skin and gums, improves skin metabolism, slimming, promotes blood circulation, It is useful as a composition for oral intake in the form of a chewing gum excellent in effects such as lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression, and anti-aging. In addition, this product can be marketed with these effects. In addition, this product has no side effects even when taken for a long time and can be used with confidence.

<Elastase activity inhibitor>
Based on the following formulation, a solid elastase activity inhibitor was prepared by a conventional method.
(Prescription) (%)
Ginkgo biloba extract powder 30
Barley young leaves 20
Lactosucrose-containing sugar powder (Hayashibara Shoji Sales,
Product name “milk oligo LS-90P”) 13.5
Reduced maltose (sales of Hayashibara Corporation,
Product name "Powder Mabit" 13.5
Glycosylnarindin (manufactured by Hayashibara Biochemical Research Institute,
(Purity of glucosylnardin 65%) 1.25
Glucose transfer hesperidin (Hayashibara Biochemical Laboratories, Inc.,
Product name "Alpha Glucosyl Hesperidin") 15
Glucose transfer ascorbic acid (Hayashibara Corporation sales,
Product name "ASCO Fresh") 2
Bittern extract 3.5
L-citrulline 1
Fragrance Appropriate amount of pigment Appropriate amount is 100%.

  Since this product contains glycerinated naringin and glycated hesperidin, it has excellent skin wrinkle-suppressing effects, retains the elasticity and elasticity of the skin and gums, improves skin metabolism, slimming, promotes blood circulation, It is useful as a composition for oral ingestion in the form of a powder excellent in effects such as lipase activity inhibition, radical removal, anti-inflammation, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction suppression and anti-aging. In addition, this product can be marketed with these effects. In addition, this product has no side effects even when taken for a long time and can be used with confidence.

<Elastase activity inhibitor>
The following ingredients were blended to obtain an elastase activity inhibitor in the form of an oral liquid food.
(Prescription) (%)
Lactosucrose 5
Glycosylnarizine (manufactured by Hayashibara Biochemical Research Institute,
(Purity of glucosylnarindin 65%) 5
Glucose transfer hesperidin (Hayashibara Biochemical Laboratories, Inc.,
Product name “Hayashibara Hesperidin S”) 5
Nonfat dry milk 37
Whole milk powder 12
Malt tetraose high content water tank 40
Indigestible dextrin (Matsuya Chemical Co., Ltd. sales,
Product name "Fiber Sol 2") 0.5
α, α-trehalose 3
Glucose transfer ascorbic acid (Hayashibara Corporation sales,
Product name "ASCO Fresh") 1
L-citrulline 1
Vitamin A Appropriate vitamin D Appropriate amount Thiamine hydrochloride Appropriate amount Riboflavin Appropriate amount Pyridoxine hydrochloride Appropriate amount Cyanocobalamin Appropriate amount Choline hydrogen tartrate Appropriate amount Nicotinamide Amide Appropriate amount Tocopherol acetate Appropriate amount Iron sulfate Appropriate amount Calcium hydrogen phosphate Appropriate amount Dissolve this product in an appropriate amount of water Ingestion can provide nutrition for patients who cannot take a normal meal, and this product contains glycated naringin and glycated hesperidin. Maintain gum and elasticity of gums, improve skin metabolism, slimming, blood circulation promotion, lipase activity inhibition, radical removal, anti-inflammatory, whitening, in vivo lipid peroxide reduction, in vivo ascorbic acid reduction inhibition, anti It is useful as a composition for oral intake that is excellent in effects such as aging. In addition, this product can be marketed with these effects. In addition, this product has no side effects even when taken for a long time and can be used with confidence.

  As described above, the elastase activity inhibitor of the present invention containing one or more vitamin P as an active ingredient is not only an elastase activity inhibitory action, but also a slimming action, a blood circulation promoting action, a lipase activity inhibiting activity, a radical It has various physiological activities such as removal action, anti-inflammatory action, whitening action, etc., and when used on the skin, it can suppress the generation of wrinkles and recover / maintain the tension and elasticity of the skin. In addition, the elastase activity inhibitor of the present invention suppresses inflammation in the skin at the site of use and its vicinity, improves blood circulation, prevents skin dullness, and also exhibits an effect on the decomposition of excess fat. It has an excellent effect of preventing aging and maintaining a youthful skin condition. Furthermore, the elastase activity inhibitor of the present invention has various physiological functions such as a slimming action, a blood circulation promoting action, a lipase activity inhibiting action, a radical scavenging action, an anti-inflammatory action, a living in vivo lipid peroxide reducing action, an in vivo ascorbic acid reduction inhibiting action. It has an action and can be used for the oxidation prevention of the sebum component of the skin, the oxidation disorder of the skin, the protection of the skin, the acne treatment, the periodontal disease treatment and the like. In addition, the elastase activity inhibitor of the present invention containing one or more of vitamin P as an active ingredient has no side effects, is safe and excellent in feeling of use, and should be used comfortably for a long time. Can do. The present invention is an invention that exhibits such remarkable effects, and is a truly significant invention that contributes greatly to the world.

Claims (6)

  An elastase activity inhibitor containing vitamin P as an active ingredient.   Vitamin P is naringin, hesperidin, rutin, esculin, or enzymatic degradation of these enzyme degradation products, such as purnin, naringenin, β-glucosyl hesperetin, hesperetin, isoquercitrin, quercetin, esculetin, or vitamin P or vitamin P The elastase activity inhibitor according to claim 1, wherein the elastase activity inhibitor is one or more selected from sugar transfer products.   Along with vitamin P, it contains any one or more selected from cyanobacteria extract, cyclonigerosyl nigerose, L-ascorbic acid-2-glucoside, and photosensitizer 101. The elastase activity inhibitor according to Item.   Further, surfactants, preservatives (antibacterial agents), moisturizers, thickeners, water-soluble polymers, antioxidants, chelating agents, dyes, fragrances, pH adjusters, vitamins other than vitamin P 1 The elastase activity inhibitor according to any one of claims 1 to 3, comprising a seed or two or more kinds.   The anti-wrinkle agent, anti-kojiwa agent, slimming promoter, blood circulation promoter, lipase activity inhibitor, anti-inflammatory agent, radical scavenger of the elastase activity inhibitor according to any one of claims 1 to 4. , Whitening agent, in vivo lipid peroxide reducing agent, in vivo ascorbic acid reduction inhibitor, anti-aging agent, and body fat reducing agent. An external preparation for skin or a composition for oral consumption, which is based on the action and effect of the elastase activity inhibitor according to any one of claims 1 to 5.