JP2012207015A - Elastase activity inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new elastase activity inhibitor.SOLUTION: The elastase activity inhibitor contains pyrroloquinoline quinone or a physiologically acceptable salt thereof as an active ingredient.

Description

  The present invention relates to an elastase activity inhibitor used as a cosmetic composition, a food composition, and the like, and an agent for improving skin firmness or preventing or improving skin wrinkles or talmi.

In the living body, elastin is widely distributed in organs that require stretchability, such as ligaments, blood vessel walls, lungs, skin dermis, and joints. Elastin plays a role of imparting elasticity to the tissues of these organs, and plays a major role in maintaining elasticity or elasticity in the skin.
It is known that the amount of elastin gradually decreases due to aging, ultraviolet rays, active oxygen, stress and the like. In the skin, it has been shown that the loss of elastin gradually loses the elasticity of the skin, causing wrinkles or sagging, which is a major contributor to aging.
Among elastases that degrade and reduce elastin, elastases involved in the degradation of elastin present in the dermal matrix of the skin are known as elastase derived from neutrophils and elastase derived from fibroblasts. It is known that elastase derived from fibroblasts degrades elastin constituting elastic fibers involved in maintaining skin elasticity. Therefore, it is predicted that a high anti-wrinkle effect can be obtained by inhibiting the activity.

  The main object of the present invention is to provide a novel elastase activity inhibitor.

The present inventor has conducted research to solve the above-mentioned problems, and found that pyrroloquinoline quinone (hereinafter sometimes abbreviated as “PQQ”) inhibits the activity of elastase that degrades elastin.
The present invention has been completed based on the above findings, and provides the following elastase activity inhibitors.

Item 1. An elastase activity inhibitor comprising pyrroloquinoline quinone or a physiologically acceptable salt thereof as an active ingredient.
Item 2. Item 2. The elastase activity inhibitor according to Item 1, wherein the elastase is fibroblast-derived elastase.
Item 3. Item 3. The elastase activity inhibitor according to Item 1 or 2, comprising 0.00001 to 10% by weight of pyrroloquinoline quinone or a physiologically acceptable salt thereof.
Item 4. Item 4. The elastase activity inhibitor according to any one of Items 1 to 3, which is a cosmetic composition.
Item 5. An agent for improving skin firmness or preventing or improving skin wrinkles or tarmi, comprising pyrroloquinoline quinone or a physiologically acceptable salt thereof as an active ingredient.
Item 6. Item 6. The agent for improving skin firmness or preventing or improving skin wrinkles or talmi according to Item 5, comprising 0.00001 to 10% by weight of pyrroloquinoline quinone or a physiologically acceptable salt thereof.
Item 7. Item 7. The agent for improving skin firmness according to Item 5 or 6, or preventing or improving skin wrinkles or tarmi, which is a cosmetic composition.

  The elastase activity inhibitor of the present invention, when used as a cosmetic composition or a food composition, effectively improves the elasticity of the skin, gives the skin firmness or gloss, / Or dullness can be prevented or ameliorated. Therefore, the elastase activity inhibitor of the present invention can be used for imparting firmness or gloss to the skin, or for preventing or improving skin talmi or dullness.

It is a figure which shows that PQQ suppresses the activity of the elastase derived from a human skin fibroblast. It is a figure which shows that PQQ suppresses the activity of the elastase derived from a human skin fibroblast, or the synthesis | combination of the elastase derived from a human skin fibroblast.

Hereinafter, the present invention will be described in detail.
The elastase activity inhibitor of the present invention contains PQQ or a physiologically acceptable salt thereof (hereinafter sometimes abbreviated as “salt”) as an active ingredient.
As for elastase, neutrophil-derived elastase and fibroblast-derived elastase are typically known that decompose microorganisms or foreign substances in the living body to protect the living body. The elastase activity inhibitor of the present invention inhibits the activity of elastase derived from any cell, but particularly effectively inhibits the activity of elastase derived from fibroblasts, particularly elastase derived from skin fibroblasts. That is, the elastase activity inhibitor of the present invention effectively inhibits skin elastase.

PQQ or its salt PQQ is a redox coenzyme essential for the energy acquisition system of organisms. Since PQQ exists in various organisms such as animals, plants, and bacteria, it can be extracted from various organisms. Moreover, PQQ can purchase a commercial item.
Examples of the salt of PQQ include, but are not limited to, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt. Among the salts, sodium salt, potassium salt, calcium salt, and magnesium salt are preferable.

Cosmetic composition
<Form of cosmetic composition>
The elastase activity inhibitor of the present invention can be made into a cosmetic composition by mixing PQQ or a salt thereof with a known base or carrier acceptable as a cosmetic ingredient.
The form of the cosmetic composition is not particularly limited. For example, sheets such as liquids, suspensions, emulsions, creams, ointments, gels, liniments, lotions, aerosols, powders, poultices, non-woven fabrics, etc. Examples thereof include a sheet agent impregnated with a chemical solution and a stick agent such as a lipstick. Of these, liquids, suspensions, emulsions, creams, ointments, gels, and lotions are preferred, and liquids, emulsions, creams, gels, and lotions are more preferred in terms of good usability.
Further, the specific use of the cosmetic composition is not particularly limited. For example, foundations such as lotion, milky lotion, cream, cosmetic liquid, sunscreen cosmetics, packs, hand creams, body lotions, and body creams. Cosmetics; cleansing cosmetics such as facial cleansers, makeup removers, body shampoos, shampoos and rinses; makeup cosmetics such as foundations, makeup bases, lip balms, lipsticks and teak colors; and bathing agents Can be mentioned.

<PQQ content>
The content of PQQ in the cosmetic composition is preferably 0.00001% by weight or more, more preferably 0.0001% by weight or more, and still more preferably 0.001% by weight or more based on the total amount of the composition. Moreover, 10 weight% or less is preferable, 1 weight% or less is more preferable, and 0.3 weight% or less is still more preferable. If it is the said range, sufficient elastase activity inhibitory effect will be acquired with the normal usage-amount of cosmetics.
In addition, the content of PQQ in the cosmetic composition is preferably 0.00001 to 10% by weight, more preferably 0.0001 to 1% by weight, and more preferably 0.001 to 0% with respect to the total amount of the composition. Even more preferred is 3 wt%.

<Base / Carrier>
Examples of the base or carrier include, but are not limited to, paraffin, liquid paraffin, squalane, white wax, gelled hydrocarbon (such as plastic base), ozokerite, ceresin, petrolatum, hard fat, microcrystalline wax, α-olefin. Oligomers and hydrocarbons such as light liquid paraffin; fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and isostearic acid; glyceryl tri-2-ethylhexanoate (trioctanoin), and tri Tri-fatty acid glycerides such as (caprylic acid / capric acid) glyceryl; higher alcohols such as cetanol, stearyl alcohol, and behenyl alcohol; methyl polysiloxane, highly polymerized methyl polysiloxane, dimethyl siloxane Methyl (polyoxyethylene) siloxane / methyl (polyoxypropylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxyethylene) siloxane copolymer, dimethylsiloxane / methyl (polyoxypropylene) siloxane copolymer, polyoxyethylene・ Methyl polysiloxane copolymer, poly (oxyethylene / oxypropylene) / methyl polysiloxane copolymer, dimethyl siloxane / methyl cetyloxy siloxane copolymer, dimethyl siloxane / methyl stearoxy siloxane copolymer, alkyl acrylate copolymer Polymer methylpolysiloxane ester, crosslinked methylpolysiloxane, crosslinked methylphenylpolysiloxane, crosslinked polyether-modified silicone, crosslinked alkylpolyether-modified silicone, crosslinked Type alkyl-modified silicone, decamethylcyclopentasiloxane, ethyltrisiloxane, methyltrimethicone, methylsiloxane network polymer, polyoxyethylene / methylpolysiloxane copolymer, methylhydrogenpolysiloxane, triethoxysilylethylpolydimethylsiloxyethylhexyl Silicone oils such as dimethicone and dimethylpolysiloxane; ethylene glycol monoacetate, ethylene glycol diacetate, triethylene glycol diacetate, hexylene glycol diacetate, and 2-methyl-2-propene-1,1 A glycol acetate such as diol diacetate; triethylene glycol divalerate, 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, and Glycol esters such as 1,2,4-trimethyl-1,3-pentanediol diisobutyrate; ethylene glycol diacrylate, diethylene glycol diacrylate, propylene glycol monoacrylate, 2,2-dimethyl-trimethylene glycol diacrylate And glycol acrylates such as 1,3-butylene glycol diacrylate; glycol dinitrates such as ethylene glycol dinitrate, diethylene glycol dinitrate, triethylene glycol dinitrate, and propylene glycol dinitrate; 2,2 ′ -[1,4-phenylenedioxy] diethanol; cellulose derivatives such as ethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose Polyvinyl pyrrolidone; carrageenan; polyvinyl butyrate; polyethylene glycol; dioxane; butylene glycol adipate polyester; isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and pentaerythrisol tetra-2-ethylhexanoate Esters such as elite; polysaccharides such as dextrin and maltodextrin; lower alcohols such as ethanol and isopropanol; ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol Monoethyl ether, diethylene glycol monopropy And glycol ethers such as diether glycol, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; and aqueous bases such as water.

Among them, hydrocarbons (particularly α-olefin oligomers, squalane, light liquid paraffin, and liquid paraffin), trifatty acid glycerides (particularly glyceryl tri-2-ethylhexanoate, and tri (caprylic / capric acid) glyceryl), higher grades Alcohol (especially cetanol, stearyl alcohol, and behenyl alcohol), silicone oil (especially methylpolysiloxane, alkyl acrylate copolymer methylpolysiloxane ester, cross-linked methylpolysiloxane, decamethylcyclopentasiloxane, ethyltrisiloxane, methyl Trimethicone, methylsiloxane network polymer, polyoxyethylene / methylpolysiloxane copolymer, methylhydrogenpolysiloxane, triethoxysilylethylpolydimethylsiloxyethylhexyl dimethyl ester And dimethylpolysiloxane), esters (especially isononyl isononanoate, and pentaerythritol tetra-2-ethylhexanoate), polysaccharides (especially dextrin and maltodextrin), glycol ethers (especially diethylene glycol monoethyl ether) ), As well as water.
A base or a carrier can be used alone or in combination of two or more.

<Additives>
In addition, the cosmetic composition is a known additive added to the cosmetic within a range not impairing the effects of the present invention, for example, a surfactant, a thickener, a preservative, a pH adjuster, a chelating agent, Stabilizers, irritation reducers, preservatives, colorants, dispersants, fragrances, pearlescent agents, and the like can be added. An additive can be used individually by 1 type or in combination of 2 or more types.

  Examples of the surfactant include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexylate, and diglycerol sorbitan tetra-2-ethylhexylate. Sorbitan fatty acid esters such as: glyceryl monostearate and glyceryl fatty acids such as glyceryl monostearate malate; polyglyceryl fatty acids such as polyglyceryl monostearate, polyglyceryl monoisostearate, and polyglyceryl diisostearate; monostearin Propylene glycol fatty acid esters such as propylene glycol acid; polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene Hydrogenated castor oil derivatives such as hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), and polyoxyethylene hydrogenated castor oil 80; polyoxyethylene (20) sorbitan monolaurate Polyoxys such as (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), and polyoxyethylene (20) sorbitan isostearate Ethylene sorbitan fatty acid esters; polyoxyethylene mono coconut oil fatty acid glyceryl; glycerin alkyl ether; alkyl glucoside; polyoxyalkylene alkyl ether such as polyoxyethylene cetyl ether; Amines such as lylamine and oleylamine; silicone surfactants such as polyoxyethylene-methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG-9 polydimethylsiloxyethyl dimethicone Can be mentioned.

  Among them, glycerin fatty acids (particularly glyceryl monostearate), polyglycerin fatty acids (particularly polyglyceryl monostearate), hardened castor oil derivatives (particularly polyoxyethylene hardened castor oil 50 (HCO-50), polyoxyethylene) Hydrogenated castor oil 60 (HCO-60)), polyoxyethylene sorbitan fatty acid esters (particularly polyoxyethylene (20) sorbitan isostearate and polyoxyethylene (20) sorbitan monostearate (polysorbate 60)), polyoxy Alkylene alkyl ethers (especially polyoxyethylene cetyl ether) and silicone surfactants (especially polyoxyethylene methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, and PEG) -9 polydimethylsiloxyethyl dimethicone) is preferred.

Examples of the thickener include guar gum, locust bean gum, carrageenan, xanthan gum, dextran, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium alginate, propylene glycol alginate, polyvinyl Alcohol, polyvinyl pyrrolidone, polyvinyl methyl ether, carboxy vinyl polymer, alkyl methacrylate copolymer, sodium polyacrylate, polyethylene glycol, bentonite, dextrin fatty acid ester, pectin, (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer The Chill distearyl ammonium hectorite, (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer, polyethylene glycol distearate, triisostearate, ethylene glycol, and triisostearate, polyoxyethylene (20) and the like methyl glucoside.
Among them, xanthan gum, alkyl methacrylate methacrylate copolymer, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyethylene glycol, carboxyvinyl polymer, (hydroxyethyl acrylate / acryloyldimethyltaurine Na) copolymer, dimethyl distearyl ammonium hectorite , (Acryloyldimethyltaurate ammonium / vinylpyrrolidone) copolymer, polyethylene glycol distearate, ethylene glycol triisostearate, and polyoxyethylene (20) methylglucoside triisostearate.

  Examples of preservatives or preservatives include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, butyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, Examples include benzyl paraoxybenzoate, methyl paraoxybenzoate, and phenoxyethanol. Of these, methyl paraoxybenzoate, propyl paraoxybenzoate, and phenoxyethanol are preferred.

  Examples of pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, phosphoric acid, polyphosphoric acid, boric acid, etc.), organic acids (lactic acid, acetic acid, citric acid, sodium citrate, tartaric acid, malic acid, succinic acid, succinic acid, etc. Acid sodium, oxalic acid, gluconic acid, fumaric acid, propionic acid, acetic acid, aspartic acid, epsilon-aminocaproic acid, glutamic acid, and aminoethylsulfonic acid), gluconolactone, ammonium acetate, inorganic base (sodium bicarbonate, carbonic acid) Sodium, potassium hydroxide, sodium hydroxide, calcium hydroxide, and magnesium hydroxide), and organic bases (such as monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, and lysine). Among these, succinic acid, sodium succinate, citric acid, sodium citrate, triethanolamine, potassium hydroxide, and sodium hydroxide are preferable.

Examples of the chelating agent include ethylenediaminetetraacetic acid (edetic acid), ethylenediaminetetraacetic acid salt (sodium salt (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium salt, etc.), phytic acid, gluconic acid, polyphosphorus An acid, metaphosphoric acid, etc. are mentioned. Of these, sodium edetate is preferable.
Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene, and butylhydroxyanisole.
Examples of the irritation reducing agent include licorice extract, sodium alginate, and 2-methacryloyloxyethyl phosphorylcholine.

Examples of the colorant include inorganic pigments and natural pigments.
Examples of the pearl luster imparting agent include ethylene glycol distearate, ethylene glycol monostearate, and triethylene glycol distearate. Of these, ethylene glycol distearate is preferable.

<Other active ingredients>
In the cosmetic composition, as long as the effect of the present invention is not hindered, for example, antioxidant component, anti-aging component, anti-inflammatory component, whitening component, keratin soft component, cell activation component, vitamins, blood circulation promoting component, Add other active ingredients that can be added to cosmetics such as moisturizing ingredients, ingredients that prevent and / or repair DNA damage, UV absorbing ingredients, UV scattering ingredients, cleaning ingredients, antibacterial ingredients, and astringent ingredients Can do. Other active ingredients can be used singly or in combination of two or more.

  Examples of the antioxidant component include components derived from plants (eg, grape, ginseng, or comfrey); proanthocyanidins, tocopherols and derivatives thereof, ascorbic acid and derivatives thereof, hesperidin, glucosyl hesperidin, ergothioneine, hydrogen sulfite Examples include sodium, erythorbic acid and salts thereof, flavonoids, glutathione, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase, thioredoxin, taurine, thiotaurine, and hypotaurine. Among them, grape seed extract, grape leaf extract, ginseng extract, comfrey leaf extract, proanthocyanidins, tocopherol and its derivatives (particularly δ-tocopherol and α-tocopherol), ascorbic acid and its derivatives (particularly ascorbic acid, ascorbine) Sodium acid phosphate, magnesium ascorbate, and ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), hesperidin, glucosyl hesperidin, and ergothioneine are preferred.

  Antiaging components include, for example, hydrolyzed soy protein, retinoid (retinol and its derivatives, retinoic acid, retinal, etc.), pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivative, silicon, silicic acid, N-methyl -L-serine, mevalonolactone and the like. Of these, artemia extract, hydrolyzed soy protein, retinol, retinol acetate, and retinol palmitate are preferred.

  Anti-inflammatory components include, for example, components derived from plants (eg, Comfrey); allantoin, calamine, glycyrrhizic acid or derivatives thereof, glycyrrhetinic acid or derivatives thereof, zinc oxide, guaiazulene, pyridoxine hydrochloride, menthol, camphor, turpentine oil , Indomethacin, and salicylic acid or derivatives thereof. Of these, Comfrey leaf extract, allantoin, dipotassium glycyrrhizinate, and stearyl glycyrrhetinate are preferable.

  Examples of the whitening component include arbutin, hydroquinone, kojic acid, ellagic acid, phytic acid, lucinol, chamomile ET, ascorbic acid or a derivative thereof, vitamin E or a derivative thereof, pantothenic acid or a derivative thereof, tranexamic acid, and a whitening action. Examples thereof include plant components (for example, plant extracts or essential oils). Among these, arbutin, hydroquinone, kojic acid, ascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, ascorbyl tetraisopalmitate (tetracordylhexyldecanoate) and tranexamic acid are preferable.

  Examples of the keratin soft component include lanolin, urea, phytic acid, lactic acid, lactate, glycolic acid, salicylic acid, malic acid, and citric acid. Of these, lactic acid, sodium lactate, glycolic acid, salicylic acid, and phytic acid are preferred.

  Examples of the cell activation component include components derived from plants (for example, bilberry); amino acids such as γ-aminobutyric acid and ε-aminoproic acid; retinol and derivatives thereof, thiamine, riboflavin, pyridoxine hydrochloride, and pantothenic acids Such as vitamins such as glycolic acid and lactic acid; tannins; flavonoids; saponins; allantoins; Among them, bilberry leaf extract, retinol, retinol acetate, and retinol palmitate are preferable.

  Vitamins include, for example, retinol derivatives such as retinol, retinol acetate and retinol palmitate, retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinol retinoic acid, d-δ-tocopheryl retinoate, α-tocotic acid. Vitamin A such as ferryl retinoate and β-tocopheryl retinoate; provitamin A such as β-carotene, α-carotene, γ-carotene, δ-carotene, lycopene, zeaxanthin, cryptoxanthine, and echinone; δ Vitamin Es such as tocopherol, α-tocopherol, β-tocopherol, dl-α-tocopherol succinate, dl-α-tocopherol calcium succinate, δ-tocopherol and tocopherol nicotinate; riboflavin, flavinmo Vitamin B2s such as nucleotides, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, sodium riboflavin 5′-phosphate, and riboflavin tetranicotinate; methyl nicotinate, nicotinic acid, nicotinamide, and the like Nicotinic acids: ascorbyl stearate, L-ascorbyl dipalmitate, ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate), ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, ascorbic acid phosphate Vitamin Cs such as ester magnesium and ascorbic acid glucoside; methyl hesperidin, ergocalciferol, and cholecalc Vitamin D such as cipherol; vitamin K such as phylloquinone and farnoquinone; dibenzoyl thiamine, dibenzoyl thiamine hydrochloride, thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, thiamine nitrate, thiamine Monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, and thiamine triphosphate monophosphate Vitamin B1 such as salt; Vitamin B6 such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, 5'-pyridoxal phosphate, and pyridoxamine hydrochloride, cyanocobalamin, hydroxocoba Vitamin B12 such as min and deoxyadenosylcobalamin; folic acid such as folic acid and pteroylglutamic acid; pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-pantethein, D-panthetin, coenzyme A And pantothenic acids such as pantothenyl ethyl ether; biotins such as biotin and biocytin; and vitamin-like agents such as carnitine, ferulic acid, α-lipoic acid, orotic acid, and γ-oryzanol.

  Among them, vitamin A such as retinol, retinol acetate, and retinol palmitate; ascorbic acid, sodium ascorbate phosphate, magnesium ascorbate phosphate, and ascorbyl tetraisopalmitate (ascorbyl tetra-2-hexyldecanoate) Vitamin Cs; vitamin Es such as δ-tocopherol and nicotinic acid tocopherol; and nicotinic acids such as nicotinamide are preferred.

  Examples of the blood circulation promoting component include plants (e.g., ginseng, ashitaba, arnica, ginkgo, fennel, enmelio, Dutch oak, chamomile, roman chamomile, carrot, gentian, burdock, rice, hawthorn, shiitake, hawthorn, papaver, Senkyu, assembly, thyme, clove, chimpi, spruce, spruce, spruce, carrot, garlic, butcher bloom, grapes, buttons, maronier, melissa, yuzu, yokuinin, rosemary, rosehip, chimpi, spruce, spruce, peach, apricot , Walnuts, or corn); tocopherol nicotinate; glucosyl hesperidin; and hesperidin. Among these, ginseng extract, tocopherol nicotinate, glucosyl hesperidin, and hesperidin are preferable.

  Examples of moisturizing components include components derived from plants (for example, Tigaya); amino acids and derivatives thereof such as alanine, serine, leucine, isoleucine, threonine, glycine, proline, hydroxyproline, glucosamine, and theanine; collagen, gelatin And proteins such as elastin, or hydrolysates thereof; polyhydric alcohols such as glycerin, 1,3-butylene glycol, propylene glycol, polyethylene glycol, dipropylene glycol, and diglycerine; sugars such as sorbitol Phospholipids such as alcohol; lecithin and hydrogenated lecithin; mucopolysaccharides such as hyaluronic acid, sodium hyaluronate, acetyl hyaluronic acid, sodium acetyl hyaluronate, heparin, and chondroitin NMF-derived components such as lactic acid, sodium pyrrolidonecarboxylate, and urea; polyglutamic acid; a polymer having a phospholipid polar group such as MPC polymer (for example, LIPIDURE (registered trademark)); polyoxypropylene methyl glucoside; trimethyl Examples thereof include glycine (betaine); hydroxyethylurea; acrylic acid / acrylamide / dimethyldiallylammonium chloride copolymer; and sorbitol. Among them, chigaya root extract, hydrolyzed collagen, hydrolyzed elastin, MPC polymer glycerin, 1,3-butylene glycol, polyethylene glycol, dipropylene glycol, diglycerin, polyoxypropylene methyl glucoside, trimethyl glycine (betaine), hydroxyethyl urea Acrylic acid / acrylamide / dimethyldiallylammonium chloride copolymer, hydrogenated lecithin, hyaluronic acid, sodium hyaluronate, acetyl hyaluronic acid, sodium acetyl hyaluronate, and sorbitol are preferred.

  Examples of components having an action of preventing and / or repairing DNA damage include, for example, components derived from animals (eg, Artemia); components derived from plants (eg, cat's claw); and DNA, DNA salts, RNA, and Examples include nucleic acid components such as RNA salts. Among these, artemia extract and DNA-Na are preferable.

  Examples of the ultraviolet absorbing component include 2-methoxyhexyl paramethoxycinnamate, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, 2,4,6-tris [4- (2-ethylhexyl). Oxycarbonyl) anilino] -1,3,5-triazine, 2-ethylhexyl dimethoxybenzylideneoxoimidazolidinepropionate, and 2,4-bis-[{4- (2-ethylhexyloxy) -2-hydroxy} -phenyl] And -6- (4-methoxyphenyl) -1,3,5-triazine. Among them, 2-methoxyhexyl paramethoxycinnamate, 2- [4- (diethylamino) -2-hydroxybenzoyl] benzoic acid hexyl ester, and 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] -1,3,5-triazine is preferred.

  Examples of the ultraviolet scattering component include inorganic compounds such as zinc oxide, titanium oxide, iron oxide, cerium oxide, zirconium oxide, titanium silicate, zinc silicate, anhydrous silicic acid, cerium silicate, and hydrous silicic acid. . Also, those inorganic compounds coated with an inorganic powder such as hydrous silicate, aluminum hydroxide, mica, or talc, and those inorganic compounds as resin powders such as polyamide, polyethylene, polyester, polystyrene, or nylon Examples include composites, and those obtained by treating those inorganic compounds with silicon oil or fatty acid aluminum salts. Of these, inorganic compounds such as zinc oxide, titanium oxide, and iron oxide, and inorganic powders such as aluminum hydroxide, hydrous silicic acid, mica, or talc, or those coated with silicon oil are preferable.

  Examples of the cleaning component include polyoxyalkylene alkyl (or alkenyl) ether sulfate, alkyl (or alkenyl) sulfate, higher fatty acid salt, ether carboxylate, amide ether carboxylate, alkyl phosphate ester salt, N- Anionic surfactants such as acyl amino acid salts, polyoxyalkylene fatty acid amide ether sulfates, acylated isethionates, and acylated taurates; amine oxides, glycerin fatty acid esters, sorbitan fatty acid esters, alkyl saccharides, polyoxyalkylene alkyl ethers, Nonionic surfactants such as fatty acid alkanolamides and polyoxyalkylene hydrogenated castor oil; mono- or di-long chains optionally having alkylene oxide attached thereto and having straight-chain or branched long-chain alkyl groups Alkyl cationic surfactants such as quaternary ammonium salts; carboxymethyl betaine, sulfobetaine, imidazolinium betaine, and amphoteric surfactants such as amide betaine.

  Among these, anionic surfactants, nonionic surfactants, and amphoteric surfactants are preferable. Anionic surfactants include higher fatty acid salts (particularly salts of higher fatty acids such as palmitic acid, lauric acid, myristic acid and stearic acid), and N-acyl amino acid salts (particularly sodium N-lauroyl aspartate, hydroxylated). Potassium / N-coconut oil fatty acid potassium acylglutamate, coconut oil fatty acid acylglycine sodium, and myristoyl glutamic acid) are preferred. Of the nonionic surfactants, fatty acid alkanolamides (especially coconut oil fatty acid diethanolamide and coconut oil fatty acid monoethanolamide) and amine oxides (especially coconut oil alkyl dimethylamine oxide and lauryl dimethylamine oxide) are preferred. Amphoteric surfactants include imidazolinium betaines (particularly 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolium betaine and N-coconut oil fatty acid acyl-N-carboxymethoxyethyl-N-carboxymethylethylenediamine). Sodium) is preferred.

  Antibacterial components include, for example, chlorhexidine, salicylic acid, benzalkonium chloride, acrinol, ethanol, benzethonium chloride, cresol, gluconic acid and its derivatives, popidone iodine, potassium iodide, iodine, isopropylmethylphenol, triclocarban, triclosan, photosensitizer No. 101, Photosensitizer 201, Paraben, phenoxyethanol, 1,2-pentanediol, and alkyldiaminoglycine hydrochloride. Among them, benzalkonium chloride, benzethonium chloride, gluconic acid and its derivatives, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101, photosensitizer 201, paraben, phenoxyethanol, 1,2-pentanediol, and alkyldiamino hydrochloride Glycine is preferred, with benzalkonium chloride, gluconic acid and its derivatives, benzethonium chloride, and isopropylmethylphenol being more preferred.

  Examples of astringent components include metal salts such as alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, zinc sulfate, and potassium aluminum sulfate; and organic acids such as tannic acid, citric acid, lactic acid, and succinic acid be able to. Among these, alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, potassium aluminum sulfate, and tannic acid are preferable.

  The cosmetic composition of the present invention can be prepared by mixing and stirring each component according to a conventional method.

Food Composition The elastase activity inhibitor of the present invention can be a food composition.
This food composition can be suitably used as a health food or a dietary supplement (including balanced nutritional foods and supplements). Moreover, it is suitable for health functional foods (including foods for specified health use (including disease risk reduction labeling, standard-standard type), foods for condition specific health use, or foods with functional nutrition).
The dosage form is not particularly limited, but the tablet, pill, granule, powder, powder, capsule, with PQQ or a salt thereof as it is or with an excipient or additive usually used in foods. It can also be formulated into a dosage form such as an agent (including a soft capsule), a wettable powder, an emulsion, a liquid, an extract, or an elixir by a known method. Among these, preparations such as tablets, pills, powders, granules, capsules, and drops are preferable because they are easy to take and carry. Excipients or additives include fats and oils, stabilizers, emulsifiers, dispersants, suspending agents, fragrances, thickeners, sweeteners, colorants, fragrances, preservatives, antioxidants, and organic acids. Can be mentioned.

  Examples of oils and fats include natural vegetable oils such as peanut oil, cocoa butter, rice germ oil, perilla oil, and linseed oil, and hardened oils thereof, and glycerides of fatty acids (including medium chain fatty acids) (glycerides, diglycerides, triglycerides, etc.) , And beeswax. Of these, beeswax is preferred.

Examples of the emulsifier, dispersant, suspending agent, or stabilizer include polyhydric alcohols such as polyethylene glycol, propylene glycol, glycerin, and sorbitol; glycerin fatty acid esters; and sodium carboxymethyl cellulose. Among these, glycerin, glycerin fatty acid ester, and sodium carboxymethyl cellulose are preferable.
Examples of the thickener include locust bean gum, guar gum, xanthan gum, tamarind gum, pectin, and carrageenan. Of these, xanthan gum is preferable.
Examples of the sweetener include sucrose, fructose, maltose, erythritol, trehalose, maltitol, licorice extract, stevia processed sweetener, aspartame, acesulfame potassium, sorbitol, and xylitol.

Examples of the preservative include benzoic acid or a salt thereof, sorbic acid or a salt thereof, butyl paraoxybenzoate, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, and ethyl paraoxybenzoate.
Examples of the antioxidant include ascorbic acid, sodium ascorbate, ascorbic acid stearate, sodium ascorbate stearate, ascorbyl palmitate, bisulfite, sodium hyposulfite, sulfur dioxide, disodium EDTA calcium, erythorbine Examples include acids, sodium erythorbate, and tocopherols. Among these, ascorbic acid, ascorbyl palmitate, and tocopherol are preferable.

Examples of the organic acid include citric acid, succinic acid, tartaric acid, aspartic acid, lactic acid, malic acid, malonic acid, fumaric acid, and maleic acid.
An excipient | filler and a food additive can be used individually by 1 type or in combination of 2 or more types.

<Other active ingredients>
In addition to PQQ or a salt thereof, an active ingredient can be added to the preparation.
Examples of other active ingredients include vitamins such as vitamin A, vitamin B, vitamin C, vitamin E, vitamin D, and vitamin K; threonine, methionine, phenylalanine, tryptophan, lysine, glycine, Amino acids such as alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, and histidine; taurine, collagen, glucosamine, acetylglucosamine, hyaluronic acid, Isoflavones, polyphenols (eg, polyphenols derived from plants such as chestnut astringent or grape seeds), biotin, whey peptides, soybean peptides, royal jelly, γ-oryza , Orotic acid, rutin, hesperidin, carnitine, carnitine chloride, collagen peptide, elastin peptide, ceramide, lycopene, astaxanthin, lactic acid bacteria extract (eg LFK), glutathione, rutin, plant (eg cats claw, grape, ginger , Lotus, grape, melon, haematococcus algae, lychee seed, rose petal, or amler extract), ubiquinone derivative (eg, coenzyme Q10), spider web end, budreja axialis leaf extract, grape seed Examples include extract, grape leaf extract, ginseng extract, comfrey leaf extract, proanthocyanidins, hesperidin, glucosyl hesperidin, and ergothioneine.

Here, examples of vitamin A include retinal, retinol, retinoic acid, carotene, dehydroretinal, and lycopene.
Vitamin Bs include bis-thiamine, thiamine disulfide, thiamine dicetyl sulfate, benfotiamine, prosultiamine, fursultiamine, bisbenchamine, chicotiamine, octothiamine, alliamine, thiamine propyl disulfide, thiamine tetrahydrofurfuryl disulfide , Dicetiamine, bisibhiamine, thiamine monophosphate disulfide, thiamine pyrophosphate, chicotiamine, thiamine ethyl disulfide, thiamine propyl disulfide, riboflavin, flavin adenine dinucleotide, pyridoxine, pyridoxal, hydroxocobalamin, cyanocobalamin, methylcobalamin, deoxyadenocobalamin, folic acid , Tetrahydrofolic acid, dihydrofolic acid, nicotinic acid, nicotinic acid , Nicotinyl Nick alcohol, pantothenic acid, panthenol, exemplified biotin, choline, and inositol, and the like.
Examples of vitamin C include ascorbic acid, sodium ascorbate, ascorbic acid stearate, sodium ascorbate stearate, ascorbyl palmitate, and erythorbic acid.
Examples of vitamin Ds include ergocalciferol, cholecalciferol, hydroxycholecalciferol, dihydroxycholecalciferol, and dihydrotaxosterol. Examples of vitamin E include tocopherol and its derivatives.
Other active ingredients can be used singly or in combination of two or more.

When the food composition is formulated as described above, the content of PQQ or a salt thereof is preferably 0.00001% by weight or more, and 0.0001% by weight or more based on the whole food composition. Is more preferable, and 0.001% by weight or more is even more preferable. Moreover, 10 weight% or less is preferable, 1 weight% or less is more preferable, and 0.3 weight% or less is still more preferable. If it is the said range, PQQ or its salt which only has sufficient elastase activity inhibitory effect will be contained in the food composition of the quantity which can be taken in reasonably.
In addition, when the food composition is formulated as described above, the content of PQQ or a salt thereof is, for example, preferably 0.00001 to 10% by weight with respect to the whole food composition. 0.0001 to 1% by weight is more preferable, and 0.001 to 0.3% by weight is even more preferable.

General food composition This food composition can also be prepared by adding PQQ or a salt thereof to a general food. Examples of foods include milk, milk drinks, lactic acid bacteria drinks, soft drinks with fruit juice, carbonated drinks, vegetable juice drinks, tea drinks, fruit juice drinks, ion drinks, sports drinks, functional drinks, vitamin supplement drinks, nutrition supplement balance drinks , Beverages such as jelly beverages, alcoholic beverages, and soups; puddings such as custard pudding, milk pudding, and pudding with fruit juice, jellys, dressings, and gel-like confectionery such as creams, chewing gum, and balloons Gum-like gums (plate gum, sugar-coated grain gum, etc.), chocolates, soft candy (including caramel, nougat, gummy candy, marshmallow, etc.), caramels such as toffee, biscuits (hard biscuits, soft Biscuits, soft cookies, crackers, and semi-biscuit biscuits) and cakes Confectionery and the like; ice cream, ice milk, lacto, sherbet, and frozen desserts such as frozen desserts; bread; noodles; and such as pet food, and the like.

When the food composition is obtained by adding an active ingredient to a general food, the content of PQQ or a salt thereof is preferably 0.00001% by weight or more with respect to the whole food composition, 0.0001% by weight % Or more is more preferable, and 0.001% by weight or more is even more preferable. Moreover, 10 weight% or less is preferable, 1 weight% or less is more preferable, and 0.3 weight% or less is still more preferable. If it is the said range, PQQ or its salt which only has sufficient elastase activity inhibitory effect will be contained in the food composition of the quantity which can be taken in reasonably.
In addition, when the food composition is obtained by adding an active ingredient to a general food, the content of PQQ or a salt thereof is preferably 0.00001 to 10% by weight with respect to the whole food composition, for example. 0.0001 to 1% by weight is more preferable, and 0.001 to 0.3% by weight is even more preferable.
In the case of a general food composition, other active ingredients can be blended in addition to PQQ. As other active ingredients, for example, those exemplified as other active ingredients that can be added to formulated food compositions such as health foods or nutritional supplements can be used.

  The form of the food composition is a beverage (especially a lactic acid bacteria beverage) in terms of ease of ingestion and ease of swallowing even for consumers who are difficult or difficult to swallow (swallow) tablets, granules, capsules, etc. , Fruit juice-containing soft drinks, and functional drinks), jelly, and gel-like confectionery are preferred, and lactic acid bacteria drinks and functional drinks are more preferred.

How to Use The cosmetic composition may be applied in the usual manner of use and the number of uses.
The food composition may be taken so that the daily intake of PQQ or a salt thereof is, for example, 0.0001 mg or more, preferably 0.01 mg or more, more preferably 0.1 mg or more. Moreover, what is necessary is just to ingest so that the daily intake of PQQ or its salt may be 100 mg or less, Preferably it is 30 mg or less, More preferably, it is 10 mg or less. If it is the said intake, sufficient elastase activity inhibitory effect is acquired, and there is no possibility that the effect by excessive intake may arise.
Moreover, if a food composition is ingested so that the daily intake of PQQ or its salt may be 0.0001-100 mg, for example, Preferably it is 0.01-30 mg, More preferably, it is 0.1-10 mg. Good.
Although the use object of the agent of the present invention is not particularly limited, for cosmetic compositions, humans who are found to have reduced skin tension or elasticity, wrinkles, tarmi, gloss reduction, or skin texture reduction, and elderly people The person etc. become suitable subjects.
As for the food composition, patients having corneal disorders such as corneal ulcers, rheumatism, arthritis such as osteoarthritis, and arthritis such as osteoarthritis, or inflammatory diseases are also suitable for the food composition. It becomes a target.
Moreover, in any case of the cosmetic composition and the food composition, healthy people can also be targeted, thereby reducing skin tension or elasticity due to aging, ultraviolet rays, sunburn, excessive washing, etc. It is possible to prevent wrinkles, tarmi, gloss, or skin texture, or to prevent progression.

In addition, since PQQ or a salt thereof inhibits elastase activity, particularly skin elastase activity, the present invention includes the improvement of skin firmness or the prevention or improvement of skin wrinkles or tarmi containing PQQ or a salt thereof as an active ingredient. Includes agents.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these Examples.

Human fibroblast-derived elastase activity inhibition test (1)
Normal human adult-derived skin fibroblasts (NHDF; manufactured by Kurabo Industries), Dulbecco's minimal medium (DMEM) containing 10% fetal bovine serum, 2 × 10 2 in a 96-well microplate for cell culture (Corning) ^The cells were seeded at a density of ⁴ cells / well and cultured in a 37 ° C., 5% CO ₂ incubator for 24 hours. After removing the culture supernatant, 50 μl of 0.5% Triton X-100 aqueous solution was added, and the mixture was allowed to stand at room temperature for 30 minutes and used as a crude enzyme solution.
In this crude enzyme solution (50 μl), 0.1 M Tris-HCl buffer (pH 8.0) 50 μl (Comparative Example 2; control) and 400 μg / ml PQQ-2Na-containing 0.1 M Tris-HCl buffer (pH 8.0) were used. 50 μl (Example 1) and 50 μl of 0.1 M Tris-HCl buffer (pH 8.0) containing 0.4 μg / ml EDTA · 2Na (Wako Pure Chemical Industries) (Comparative Example 1; positive control) were added.
Further, 100 μl of the above-described Tris-HCl buffer solution containing 5 mM elastase synthesis substrate succinyl-alanyl-alanyl-alanyl-p-nitroanilide (manufactured by Peptide Institute) containing 1.5 mM PMSF was added to each well. Was 200 μl in total, and allowed to stand at 37 ° C. for 2 hours in the dark.
Absorbance at 405 nm by p-nitroaniline produced by hydrolysis with fibroblast-derived elastase was measured using an absorptiometer. The elastase inhibition rate was calculated from the following equation, where C ′ was the absorbance value in the case of only the above-described Tris-HCl buffer solution without addition of the sample, and S ′ was the absorbance value at the time of sample addition.

Fibroblast-derived elastase inhibition rate (%) = (1− (S ′ / C ′)) × 100

The results are shown in FIG. 1 and Table 1 below. From FIG. 1 and Table 1, it can be seen that PQQ or a salt thereof effectively suppresses or inhibits elastase activity.

Human fibroblast-derived elastase activity inhibition test (2)
Normal human adult skin-derived fibroblasts; a (NHDF Kurabo), fetal bovine serum using Dulbecco minimal medium (DMEM) containing 10%, 2 × 10 ⁴ to 96-well microplate for cell culture (Corning) 100 μL of a test substance (PQQ) seeded at a density of cells / well and adjusted in concentration with DMEM medium (FBS (−)) was added to the well, followed by culturing in a 37 ° C., 5% CO ₂ incubator for 48 hours. In addition, a control was also provided in which 100 μL of DMEM medium (FBS (−)) without PQQ was added to the wells and cultured in a 37 ° C., 5% CO ₂ incubator for 48 hours. After removing the culture supernatant, add 100 μl of 0.5% Triton X-100 aqueous solution to each well, maintain at 32 ° C by heating, shake for 2 hours, freeze and thaw at -20 ° C to disrupt the cell membrane What was made to use was used as a crude enzyme liquid.
To 50 μl of this crude enzyme solution, 100 μl of 0.1 M Tris-HCl buffer solution (pH 8.0) containing 5 mM elastase synthesis substrate succinyl-alanyl-alanyl-alanyl-p-nitroanilide (Peptide Institute) was added to each well. Then, after making the inside of the well 150 μl in total, it was allowed to stand at 37 ° C. for 3.5 hours in the dark.
The final concentration of PQQ in the enzyme reaction solution is 1 × 10 ⁻² w / v%, 1 × 10 ⁻³ w / v%, 1 × 10 ⁻⁴ w / v%, 1 × 10 ⁻⁵ w / v, respectively. v% and 1 × 10 ⁻⁶ w / v%.
Absorbance at 405 nm by p-nitroaniline produced by hydrolysis with fibroblast-derived elastase was measured using an absorptiometer.

  FIG. 2 shows the remaining elastase activity and the cell viability relative to the control when PQQ was added. As is clear from FIG. 2, PQQ suppressed the elastase activity remaining rate in a dose-dependent manner. Moreover, since the cell viability is not reduced by PQQ, it can be seen that the decrease in elastase activity is not due to the decrease in the number of viable cells. In this study, since the enzyme enzyme solution was prepared using normal human adult-derived skin fibroblasts cultured in the presence of PQQ, PQQ has an elastase activity suppression or inhibitory action, or an elastase synthesis inhibitory action. It has been shown.

  Since PQQ or a salt thereof inhibits elastase activity, when used as a cosmetic composition or food composition, it gives firmness or luster to the skin, and prevents and improves skin tarmi, wrinkles, or dullness. Can be suitably used.

Claims (7)

  An elastase activity inhibitor comprising pyrroloquinoline quinone or a physiologically acceptable salt thereof as an active ingredient.   The elastase activity inhibitor according to claim 1, wherein the elastase is a fibroblast-derived elastase.   The elastase activity inhibitor according to claim 1 or 2, comprising 0.00001 to 10% by weight of pyrroloquinoline quinone or a physiologically acceptable salt thereof.   The elastase activity inhibitor according to any one of claims 1 to 3, which is a cosmetic composition.   An agent for improving skin firmness or preventing or improving skin wrinkles or tarmi, comprising pyrroloquinoline quinone or a physiologically acceptable salt thereof as an active ingredient.   The agent for improving skin firmness or preventing or improving skin wrinkles or talmi according to claim 5, comprising 0.00001 to 10% by weight of pyrroloquinoline quinone or a physiologically acceptable salt thereof.   The agent for preventing or improving skin firmness or skin wrinkles or tarmi according to claim 5, which is a cosmetic composition.