JP2007284430A - Glutathione production promoting agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To find a glutathione production promoting component and provide a skin care preparation compounded with the component. <P>SOLUTION: γ-Tocopherol and δ-tocopherol have glutathione production promoting action and the action is remarkable compared with α-tocopherol having highest physiological activity. Accordingly, a useful skin care preparation imparted with excellent effects of glutathione such as antioxidation effect and cell activation effect can be produced by compounding the glutathione production promoting agent. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a glutathione production promoter and an external preparation for skin containing these.

Glutathione (L-γ-glutamyl L-cysteinylglycine) is a tripeptide that exists in mammals, and is reduced by an intramolecular SH group, acts as a coenzyme, production of mercapturic acid, and other detoxification mechanisms. Protective action of SH enzymes or other cellular components (Non-patent document 1: Progress in research on glutathione, Osamu Hayashi et al., 7-37,1969), promotion of excretion of harmful substances, enhancement of cholinesterase activity Anti-allergic action, enzyme activation action, etc. are known. However, it is important to promote production of glutathione in cells because it has a characteristic sulfur odor, precipitation occurs in the preparation, and many cells cannot incorporate glutathione. For example, a chromanone derivative (Patent Document 1: Japanese Patent Application Laid-Open No. 2003-321463) is known.
On the other hand, tocopherol is contained in biological membranes and oils and fats, and exhibits an antioxidant effect by eliminating and inactivating radicals and active oxygen. Further, the physiological activity ratio of α-, β-, γ-, and δ-tocopherol is 100: 40: 10: 1 (Non-patent Document 2: Japanese Food Standard Ingredients Table, Chapter 1-2-
2, (6) Vitamin, (3) Vitamin E) and α body are the highest and δ body is the lowest. Conversely, it is known that the antioxidant activity of fats and oils is highest in δ form and lowest in α form (Non-Patent Document 3: J. Act. Oxyg. Free Rad. 3: 531-541, 1992). Furthermore, α-tocopherol promotes glutathione production (Non-patent Document 4: Free Radical Res)
earch, 36: 705-709, 2002), but no γ or δ-tocopherol has been reported.

An object of the present invention is to find a component that promotes the production of glutathione. Another object of the present invention is to provide a skin external preparation containing a glutathione production promoting component.

As a result of intensive studies to solve the above problems, the present inventors have found that each of γ-tocopherol and δ-tocopherol has a glutathione production promoting action, and this action is higher than α-tocopherol having the highest physiological activity. And the present invention was completed.

That is, this invention is a glutathione production promoter or skin external preparation shown to the following (1)-(3).
(1) A glutathione production promoter containing γ-tocopherol and / or δ-tocopherol.
(2) A skin external preparation containing the glutathione production promoter according to (1).
(3) Further, it contains one or more selected from the group consisting of an anti-aging component and a moisturizing component, a whitening component, an anti-inflammatory component, an antibacterial component, a cell activation component, an astringent component, and an antioxidant component (
The external preparation for skin according to 1) or (2).
The present invention also includes a method for promoting glutathione production.
(4) A method for promoting glutathione production with γ-tocopherol and / or δ-tocopherol.
In the present specification, “%” means “% by weight” unless otherwise specified.

In the present invention, it has been found that each of γ-tocopherol and δ-tocopherol has a glutathione production promoting action, and that this action is more remarkable than α-tocopherol having the highest physiological activity.
Further, by incorporating these glutathione production promoters, it is possible to provide a useful skin external preparation to which the excellent effects of glutathione such as antioxidant and cell activation are added.

BEST MODE FOR CARRYING OUT THE INVENTION

The γ-tocopherol and δ-tocopherol used in the present invention can be obtained by conventional methods, and commercially available products can also be used.
The amount of γ-tocopherol and δ-tocopherol used in the present invention to the external preparation for skin is
It is not particularly limited as long as the effects of the present invention are achieved, and can be appropriately selected and used in consideration of the feeling of use and effects on the skin, but is usually 0.01 to 10% by weight, preferably with respect to the entire external preparation for skin. Is 0.1
˜8 wt%, particularly preferably 1 to 6 wt%. In addition, γ-tocopherol, δ-
Tocopherols may be used alone or in combination.

In the external preparation for skin of the present invention, for the purpose of enhancing or supplementing the effect of the present invention, an anti-aging component,
In addition, a whitening component, an anti-inflammatory component, an antibacterial component, a cell activation component, an astringent component, and an antioxidant component are added in combination of one or two or more in order to add other useful effects to the moisturizing component and the external preparation for skin. be able to. Each of these components is not particularly limited as long as it is conventionally used as a component of a skin external preparation in the pharmaceutical, quasi-drug, or cosmetic field, and is used in the future. Can be used. Particularly preferred combinations of these components include each combination of a glutathione production promoter and a moisturizing component, each combination of a glutathione production promoter and a whitening component, each of a glutathione production promoter, a moisturizing component and an antioxidant component. Combination, each combination of glutathione production promoter and anti-aging component, each combination of glutathione production promoter, anti-aging component and antioxidant component,
Examples include a combination of a glutathionic acid production promoter, a cell activation component, and an anti-aging component. Each of these components is not particularly limited as long as it is conventionally used as a component of a skin external preparation in the pharmaceutical, quasi-drug, or cosmetic field, and is used in the future. Can be used.

Antiaging components include retinoids (retinol, retinoic acid, retinal, etc.), pangamic acid, kinetin, ursolic acid, turmeric extract, sphingosine derivatives, silicon, silicic acid, N-methyl-L-serine, mevalonolactone, and the like. Preferred are retinoid (retinol, retinoic acid, retinal, etc.) and kinetin.

When using the anti-aging component, it is not particularly limited as long as the effects of the present invention are achieved, and can be appropriately selected and used in consideration of the feeling of use and effects on the skin. Usually, it is 0.0003-10 weight%, More preferably, it is 0.01-5 weight%.

As moisturizing ingredients, amino acids such as alanine, serine, leucine, isoleucine, threonine, glycine, proline, hydroxyproline, glucosamine, theanine and derivatives thereof; peptides such as gelatin; glycerin, diglycerin, 1,3-butylene glycol, propylene Polyhydric alcohols such as glycol and polyethylene glycol; ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether , Propylene glycol monopropyl ether, dipro Glycol ethers such as pyrene glycol monoethyl ether and dipropylene glycol monopropyl ether; sugar alcohols such as sorbitol; phospholipids such as lecithin (including soybean phospholipid) and hydrogenated lecithin; mucopolysaccharides such as heparin and chondroitin; lactic acid and pyrrolidone In addition to NMF-derived components such as sodium carboxylate and urea, polyglutamic acid and the like can be mentioned. Preferred are alanine, serine, glycine, proline, hydroxyproline, glucosamine, theanine, glycerin, diglycerin, 1,3-butylene glycol, hydrogenated lecithin, heparin, chondroitin,
Lactic acid, sodium pyrrolidonecarboxylate, and polyglutamic acid.

When a moisturizing component is used, it is not particularly limited as long as the effects of the present invention are achieved, and can be appropriately selected and used in consideration of the feeling of use and effects on the skin. ~ 3
0% by weight, preferably 0.5 to 10% by weight, more preferably 0.5 to 5% by weight.

As whitening ingredients, vitamins such as arbutin, hydroquinone; ellagic acid; phytic acid; lucinol; chamomile ET; vitamin A or its derivative, vitamin C or its derivative (magnesium phosphate ascorbate), pantothenic acid or its derivative, etc. Is mentioned. Among these, preferred are hydroquinone, pantothenic acid or derivatives thereof,
Examples include ellagic acid, phytic acid, vitamin A or a derivative thereof, vitamin C or a derivative thereof, and hydroquinone, vitamin C or a derivative thereof (magnesium phosphate ascorbate) can be particularly preferable. These whitening components may be used alone or in combination of two or more.

A plant component having a whitening effect may be used as a whitening component.
Iris (Iris), Almond, Aloe, Ginkgo, Oolong Tea, Ages, Ogon, Oulen, Hypericum, Adriaticus, Seaweed, Cuckoo, Gardenia, Kujin, Chlorella, Gobaishi, Wheat, Rice, Rice Haiga, Oryzanol, Rice Plant, Saisin, Salamander, Perilla, Peonies, Senkyu, Sakuhakuhi, Soybean, Natto, Tea, Toki, Toki-Senka, Garlic, Hamamelis, Safflower, Buttonpi, Yokuinin, Toki, Amethyst, Asenyaku, Acebi-warabi, Inaki, Enoki, Oyster (Diospyros kaki)
Ingredients derived from plants such as black bean, gentian, genzin, salsa, sweet bean, shokuma, jujuu, sage, zenko, radish, azalea, horsetail, tocin, oyster, parsley, holly, hops, buffalo, clove, licorice. Preferably, Iris (Iris), Aloe, Ginkgo, Oolong tea, Ages, Ogon, Oulen, Hypericum, Olysam, Seaweed, Cuckoo, Gardenia, Kujin, Gobaishi, Wheat, Rice, Rice bran, Saishin, Salamander, Perilla, Peonies, Senkyu , Sakuhakuhi, Tea, Toki, Tokinsenka, Hamelis, Safflower, Buttonpi, Yokuinin, Amethyst, Asenyaku, Enoki, Oyster, Diospyros kaki, Cattle, Black bean, Gentian,
Salsa, string beans, jujuu, sage, zenko, radish, azalea, tsukushihagi,
It is a plant-derived component of Toshin, Nigaki, Parsley, Holly, Hops, Clove, Licorice and Toki, and more preferably Iris (Iris), Aloe, Ginkgo, Ages, Ogon, Ouren, Hypericum, Gardenia, Kujin, Rice, Rice bran , Saishin, Peonies, Senkyu, Sakuhakuhi, Tea, Toki, Toshinka, Hamamelis, Safflower,
It is a plant-derived component of button pi, amethyst, asenyaku, enoki, oyster (Diospyros kaki), sage, radish, azalea, parsley, hops, licorice and yakuinin.
When these plant components are used in the external preparation for skin of the present invention, the form of the plant component is not particularly limited, but can usually be used in the form of a plant extract (plant extract), an essential oil or the like. In addition, the inside of () described in the said plant component is the kind of plant, an alias, or a crude drug name.

When using the above-mentioned whitening component, the ratio to be blended with the external preparation for skin of the present invention is preferably 0.0003.
-10% by weight, more preferably 0.01-5% by weight.
When using a plant component having a whitening effect as a whitening component, one or two are used depending on the purpose.
Species or more can be used in any combination. When the plant component is used as a whitening component, the blending ratio in the external preparation for skin of the present invention is usually 0, in terms of an extract such as extract or essential oil.
It is 00001 to 20% by weight, preferably 0.0001 to 15% by weight, more preferably 0.001 to 10% by weight.

Anti-inflammatory components include allantoin, calamine, glycyrrhizic acid or derivatives thereof, glycyrrhetinic acid or derivatives thereof, zinc oxide, guaiazulene, tocopherol acetate, pyridoxine hydrochloride, menthol, camphor, turpentine oil, indomethacin, salicylic acid or derivatives thereof. . Preferably allantoin, glycyrrhizic acid or a derivative thereof,
Glycyrrhetinic acid or its derivatives, guaiazulene and menthol.

When using the anti-inflammatory component, the proportion to be blended with the external preparation for skin of the present invention is preferably 0.00.
It is 03-10 weight%, More preferably, it is 0.01-5 weight%.

Antibacterial components include 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 Photosensitive element 201, parabens (such as methylparaben, propylparaben, and butylparaben), phenoxyethanol, 1,2-pentanediol, and alkyldiaminoglycine hydrochloride. Preferably, benzalkonium chloride, benzethonium chloride, gluconic acid and derivatives thereof, isopropylmethylphenol, triclocarban, triclosan, photosensitizer 101, photosensitizer 201, paraben (methylparaben, propylparaben, butylparaben), phenoxyethanol, 1 , 2-pentanediol,
Examples thereof include alkyldiaminoglycine hydrochloride. More preferred are benzalkonium chloride, gluconic acid and its derivatives, benzethonium chloride, and isopropylmethylphenol.

When the antibacterial component is used, the proportion to be blended with the external preparation for skin of the present invention is preferably 0.0003.
-10% by weight, more preferably 0.01-5% by weight.

Cell activation components include amino acids such as γ-aminobutyric acid and ε-aminocaproic acid: vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride and pantothenic acids: α-hydroxy acids such as glycolic acid and lactic acid: tannin, Examples include flavonoids, saponins, allantoin, and photosensitizer 301. Preferred are amino acids such as γ-aminobutyric acid and ε-aminocaproic acid: vitamins such as retinol, thiamine, riboflavin, pyridoxine hydrochloride and pantothenic acids.

When using the above-mentioned cell activation component, the ratio to be blended with the external preparation for skin of the present invention is preferably
It is 0.0003-10 weight%, More preferably, it is 0.01-5 weight%.

Convergent ingredients include alum, chlorohydroxyaluminum, aluminum chloride,
Examples include metal salts such as allantoin aluminum salt, zinc sulfate, and aluminum potassium sulfate; organic acids such as tannic acid, citric acid, lactic acid, and succinic acid. Alum, chlorohydroxyaluminum, aluminum chloride, allantoin aluminum salt, aluminum potassium sulfate, and tannic acid are preferable.

When the astringent component is used, the proportion to be blended in the external preparation for skin of the present invention is usually 0.0003 to 10% by weight, preferably 0.01 to 5% by weight, more preferably 0.01 to 5% by weight.

Antioxidant components include ascorbic acid and its derivatives (magnesium ascorbyl phosphate, ascorbyl tetraisopalmitate), butylhydroxyanisole, dibutylhydroxytoluene, sodium bisulfite, erythorbic acid and its salts, flavonoids, catalase, superoxide dismutase Thioredoxin, taurine, thiotaurine, hypotaurine, thioredoxin, flavonoids, astaxanthin and the like. Preferred are ascorbic acid and its derivatives, thiotaurine, hypotaurine, thioredoxin, flavonoids, and astaxanthin.

When the antioxidant component is used, the proportion to be blended with the external preparation for skin of the present invention is usually 0.00001 to 10% by weight, preferably 0.0001 to 5% by weight, more preferably 0.001 to 2% by weight.

In addition to the above components, the external preparation for skin of the present invention further comprises a surfactant, a gelling agent, fats and oils,
Chelating agents, sugars, and UV protection agents can also be added.

Examples of the surfactant include polyoxyethylene (hereinafter also referred to as POE) -octyldodecyl alcohol and POE-2-decyltetradecyl alcohol; POE-branched alkyl ether; POE-oleyl ether and POE-cetyl ether POE-alkyl ethers; sorbitan esters such as sorbitan monooleate, sorbitan monoisostearate and sorbitan monolaurate; POE-sorbitan monooleate, POE-sorbitan monoisostearate, and POE-sorbitan monolaurate, POE- POE-sorbitan esters such as sorbitan tetraoleate; glycerol fatty acid esters such as glycerol monooleate, glycerol monostearate (glycerol monostearate), and glycerol monomyristate; POE-glycerol monooleate POE-glycerin monostearate and POE-glycerin fatty acid esters such as POE-glycerin monomyristate; POE-cured castor oil such as POE-dihydrocholesterol ester, POE-cured castor oil, and POE-cured castor oil isostearate Fatty acid esters; POE-alkyl aryl ethers such as POE-octylphenyl ether; glycerin alkyl ethers such as monoisostearyl glyceryl ether and monomyristyl glyceryl ether; POE-glycerins such as POE-monostearyl glyceryl ether and POE-monomyristyl glyceryl ether Alkyl ethers;
Polyglycerin fatty acid esters such as diglyceryl monostearate, decaglyceryl decastate, decaglyceryl decaisostearate, and diglyceryl diisostearate; various nonionic surfactants such as sorbitan sesquioleate: or lecithin, hydrogen Examples include naturally occurring surfactants such as added lecithin, saponin, surfactin sodium, cholesterol, bile acids, and amino acid surfactants. These surfactants may be used alone or in any combination of two or more.

When a surfactant is used, the blending ratio in the external preparation for skin of the present invention is not particularly limited as long as it does not affect the skin and mucous membranes and does not interfere with the effects of the present invention. It can be appropriately selected and used in such a range that it is contained in the agent at a ratio of 0.01 to 30% by weight. From the viewpoint of the stability of the active ingredient in the external preparation for skin of the present invention and the feeling of use on the skin, the range is preferably 0.1 to 20% by weight, more preferably 0.1 to 10% by weight.

Examples of the gelling agent include carboxyvinyl polymer, polyoxyethylene / polyoxypropylene block copolymer, polyvinyl alcohol, sodium polyacrylate, sodium alginate, acrylic acid / alkyl methacrylate copolymer, and the like. These gelling agents may be used alone or in any combination of two or more.

When a gelling agent is used, the blending ratio in the external preparation for skin of the present invention is not particularly limited as long as it does not affect the skin and mucous membranes and does not interfere with the effects of the present invention. Although it can be appropriately selected and used within the range of 0.01 to 20% by weight in the external preparation, from the viewpoint of the stability of the active ingredient in the external preparation of the present invention and the feeling of skin use, etc. , Preferably 0.1 to 10% by weight, more preferably 0.5 to 5% by weight.

The fats and oils are not particularly limited as long as they are used as components of external preparations in the field of pharmaceuticals, quasi drugs and cosmetics. For example, synthetic fats and oils such as medium chain fatty acid triglycerides; soybean oil, rice oil, rapeseed oil, cottonseed oil, sesame oil, safflower oil, castor oil, olive oil, macadamia nut oil, cacao oil, coconut oil, sunflower oil, palm oil, flax oil, perilla Oil, shea oil,
Vegetable oils such as monkey oil, palm oil, tree wax, jojoba oil, grape seed oil, and avocado oil;
Animal fats such as mink oil, egg yolk oil, beef tallow, milk fat, and pork tallow; beeswax, whale wax, lanolin,
Waxes such as carnauba wax and candelilla wax; hydrocarbons such as liquid paraffin, squalene, squalane, microcrystalline wax, ceresin wax, paraffin wax, petrolatum; lauric acid, myristic acid, stearic acid, oleic acid, isostearic acid, behenine Natural and synthetic fatty acids such as acids; natural and synthetic higher alcohols such as cetanol, stearyl alcohol, hexyl decanol, octyl decanol, lauryl alcohol, behenyl alcohol; isopropyl myristate, isopropyl palmitate, octyldodecyl oleate, octyldodecyl oleate, tri Esters and ethers such as glyceryl 2-ethylhexanoate, octyl isononanoate, and cholesterol oleate; methylphenylpolysiloxane Silicone oils such as emissions and the like. These fats and oils
You may use individually by 1 type or may be used in combination of 2 or more types arbitrarily.

When these oils and fats are used, the blending ratio in the external preparation for skin of the present invention is not particularly limited as long as it does not affect the skin and mucous membranes and does not interfere with the effects of the present invention. Although it can be appropriately selected and used within the range of 0.01 to 70% by weight contained in the external preparation for skin, it is possible to use the active ingredient in the external preparation for skin according to the present invention in terms of stability and feeling of use on the skin. Therefore, the range of 0.1 to 60% by weight, more preferably 0.1 to 50% by weight can be mentioned.

The chelating agent is not particularly limited as long as it is used as a component of an external preparation in the pharmaceutical, quasi-drug or cosmetic field. Examples thereof include ethylenediaminetetraacetic acid, ascorbic acid, citric acid, phytic acid, polyphosphoric acid, metaphosphoric acid, succinic acid, and salts thereof. Among these, ethylenediaminetetraacetic acid, citric acid or a salt thereof is preferable, and ethylenediaminetetraacetic acid or a salt thereof is particularly preferable.
The salt of ethylenediaminetetraacetic acid is not particularly limited as long as it is pharmaceutically, pharmacologically or physiologically acceptable. For example, ethylenediaminetetraacetic acid sodium, ethylenediaminetetraacetic acid trisodium (edetate trisodium), Mention may be made of alkali metal salts such as disodium ethylenediaminetetraacetate and tetrasodium ethylenediaminetetraacetate.
Ethylenediaminetetraacetic acid or a salt thereof can also be used in the form of a hydrate. Specific examples of the hydrate form include disodium ethylenediaminetetraacetate (hereinafter also referred to as sodium edetate).
These chelating agents may be used alone or in any combination of two or more.

When these chelating agents are used, the blending ratio in the external preparation for skin of the present invention is not particularly limited as long as it does not affect the skin and mucous membranes and does not interfere with the effects of the present invention. Although it can be appropriately selected and used within the range of 0.0005 to 0.5% by weight contained in the external preparation for skin, it is possible to use the active ingredient in the external preparation for skin according to the present invention in terms of stability and feeling of use on the skin. Therefore, the range of 0.001 to 0.2% by weight, more preferably 0.01 to 0.1% by weight can be mentioned.

The saccharide is not particularly limited as long as it is used as a component of an external preparation in the pharmaceutical, quasi-drug or cosmetic field. For example, monosaccharides (for example, glucose, galactose, mannose, ribose, arabinose, xylose, deoxyribose, fructose, ribulose, lyxose, etc.), disaccharides (for example, sucrose, trehalose, lactose, maltose, cellobiose, etc.), oligosaccharides ( For example, lactulose, raffinose, pullulan, etc.), cellulose or derivatives thereof (for example, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose,
Nitrocellulose, cationized cellulose, etc.), high molecular sugars [for example, chondroitin sulfate, dermatan, heparan, heparin, keratan or salts thereof (for example, chondroitin sulfate sodium, dermatan sulfate, heparan sulfate, keratan sulfate, etc.) And the like, and sugar alcohols (eg, mannitol, xylitol, erythritol, pentaerythritol, maltitol, sorbitol, polydextrose, etc.), xylose, inositol, dextrin and derivatives thereof (
Dextrin palmitate, etc.), honey, brown sugar extract and the like. These saccharides may be used alone or in any combination of two or more.

The UV protection agent is not particularly limited as long as it is used as a component of an external preparation in the pharmaceutical, quasi-drug or cosmetic field. For example, inorganic such as zinc oxide, titanium oxide (crystal system: anatase, rutile or brookite), kaolin, calcium carbonate, iron oxide, cerium oxide, zirconium oxide, titanium silicate, zinc silicate, anhydrous silicic acid and cerium silicate Compounds, those inorganic compounds coated with inorganic powders such as mica and talc, compounded with resin powders such as polyamide, polyethylene, polyester, polystyrene, nylon, and silicon oil and fatty acid aluminum salts Treated, methyl diisopropylcinnamate, sinoxate, glyceryl mono-2-ethylhexanoate diparamethoxycinnamate, isopropyl dimethoxycinnamate diisopropylcinnamate ester, 2-ethylhexyl paramethoxycinnamate, Cinnamic acid such as benzyl cinnamate Ultraviolet absorbers; benzophenone ultraviolet absorbers such as oxybenzone, hydroxymethoxybenzophenone sulfonic acid, sodium hydroxymethoxybenzophenone sulfonate, dihydroxydimethoxybenzophenone, dihydroxydimethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, tetrahydroxybenzophenone; paraaminobenzoic acid, paraaminobenzoic acid Benzoate-based ultraviolet rays such as ethyl acetate, glyceryl paraaminobenzoate, amyl paradimethylaminobenzoate, 2-ethylhexyl paradimethylaminobenzoate, ethyl 4- [N, N-di (2-hydroxypropyl) amino] benzoate Absorbent: ethylene glycol salicylate, octyl salicylate, dipropylene glycol salicylate, salicylic acid Salicylic acid UV absorbers such as phenyl, homomenthyl salicylate, methyl salicylate, guaiazulene, dimethoxybenzylidenedioxoimidazolidinepropionate 2-ethylhexyl, 2,4,6-tris [4- (2-ethylhexyloxycarbonyl) anilino] 1, 3,5-triazine, parahydroxyanisole, 2- (2
-Hydroxy-5-methylphenyl) benzotriazole, 4-tert-butyl-4'-methoxydibenzoylmethane and the like. These UV protection agents may be used alone or in any combination of two or more.

The external preparation for skin of the present invention includes pharmaceuticals, quasi-drugs or cosmetics as necessary within a quantitative and qualitative range that does not impair quality such as appearance stability and viscosity and does not impair the effects of the present invention. Various components that are generally used as components of external preparations in the field, such as irritation reducers, thickeners, preservatives, colorants, dispersants, pH adjusters, and fragrances can be blended. These components may be used alone or in combination of two or more.

The external preparation for skin of the present invention is a γ-tocopherol or δ-tocopherol-containing glutathione production promoter, and if necessary, the above-mentioned optional components are blended and mixed, and if necessary, other solvents and usually used Prepared in various desired forms such as paste, mousse, gel, liquid, emulsion, cream, sheet (base material support), aerosol, spray etc. can do. These can be produced by conventional methods in the art.

The external preparation for skin of the present invention usually only has to have a liquidity of pH 1 to 8, but the stability of the preparation,
From the viewpoint of low irritation to skin and mucous membranes and good skin feeling, preferably pH 2
It is desirable to be in an acidic region of ˜7, more preferably pH 2-6.

Skin external preparation of the present invention, for example, foundation, lipstick, mascara, eye shadow,
Makeup cosmetics such as eyeliner, eyebrow, and beauty nails; milky lotion, cream, lotion,
Basic cosmetics such as oils and packs; cleansing agents such as facial cleansers, cleansing and body cleansing agents; odor control agents, athlete's foot treatment agents, antifungal agents, bactericidal disinfectants, wound healing agents, cleaning agents, cleaning agents, anti-inflammatory analgesics Various external compositions belonging to the fields of cosmetics, external medicines or external quasi-drugs, such as acne treatment agents, atopy treatment agents, hemorrhoid agents, whitening agents, and UV protection agents.
Above all, it can be used for anti-oxidation, cell activation, anti-aging (anti-wrinkle, anti-sag, etc., especially photo-aging by ultraviolet rays (anti-wrinkle, anti-sag, anti-stain etc.)), metabolism improvement, etc. Since it is expected, preferably, basic cosmetics such as emulsions, creams, lotions, oils and packs; anti-odor agents and UV protection agents are included. In addition, since free radicals such as active oxygen are considered to be involved in skin diseases, it is preferable as an external medicine to be used as an antipruritic agent, bactericidal disinfectant, wound healing agent, anti-inflammatory analgesic agent, acne treatment agent, atopy treatment agent. And immunosuppressive inhibitors due to ultraviolet rays, and skin edema inhibitors.

Further, since the present invention can promote glutathione production by containing γ-tocopherol and δ-tocopherol, “γ-tocopherol and / or δ-
It can also be referred to as a skin external preparation for promoting production of glutathione containing tocopherol.

The present invention also includes a method for promoting glutathione production using γ-tocopherol or δ-tocopherol. In the method of the present invention, promotion of glutathione production can be achieved by applying γ-tocopherol or δ-tocopherol to the skin.
In the method of the present invention, γ-tocopherol, δ-tocopherol and the content thereof are the same as those used in the above-mentioned external preparation for skin. Furthermore, the product obtained by this method can be used in known or commonly used dosages and dosages by dividing it once to several times per day according to the application.

Hereinafter, the present invention will be described in more detail based on examples and test examples, but the present invention is not limited to these examples. In the following formulations,% means weight (W / W)% unless otherwise specified.

Test Example 1 Glutathione production promotion evaluation test
Normal human epidermal keratinocytes (NHEK • F) were seeded in a 6-well plate at 9.0 × 10 ⁴ cells / well and cultured for 3 days in 3 ml of EpiLife • HKGS medium (Kurashikibo Co., Ltd.). The sample concentration was changed to 3 ml of a medium supplemented with 15 μl of a 0.02% ethanol solution of each tocopherol or 15 μl of ethanol so that the sample concentrations described in 1) were obtained. After further culturing for 24 hours, the supernatant was removed and washed with a phosphate buffer, and the number of viable cells was measured by the WST-1 method. Then, 10 mM hydrochloric acid was added to freeze and thaw, and the cell membrane was disrupted. . 5% sulfosalicylic acid was added to the treatment solution, and the amount of glutathione produced in the supernatant was quantified from the absorbance at 405 nm by an enzyme recycling measurement method (Total Glutathione Quantification Kit; DOJINDO MOLECULAR TECHNOLOGIES, INC.). From these results, the glutathione amount of Control Example 1 was set to 100, the cell survival number was 1, and the relative value = glutathione amount ratio / cell survival rate was calculated.
The results are shown in Table 1.

The amount of glutathione in Examples 1 and 2 was 1.7 times (p value 0.01%) and 1.4 times (p value 0.2%), respectively, as compared to Control Example 1. It was. On the other hand, the amount of glutathione in Control Example 2 (α-tocopherol) was 1.1 times that of Control Example 1 and a slight increase was observed. The amount of glutathione in Examples 1 and 2 compared to Control Example 2 was 1.3. Double (p value 2%) and 1.5 times (p value 3%) were both statistically significantly increased.
Therefore, it was revealed that Examples 1 and 2 have a remarkable effect of promoting glutathione production.
It is known that α has the highest physiological activity of tocopherol, but the effect of promoting the production of glutathione in cells was the highest in δ, followed by the surprising result that γ was high.

The formulation examples are given below. In addition, the compounding quantity in the following Examples represents weight% about all the things which have no description of a unit especially.

Example 3 (Gel)
δ-tocopherol 0.05
Magnesium ascorbate phosphate 3.0
Allantoin 0.1
1,3-butylene glycol 5.0
POE-hardened castor oil 60 2.0
Macadamia nut oil 1.5
Glyceryl tri-2-ethylhexanoate 1.5
Glycerol monostearate 0.5
Methylphenyl polysiloxane 0.5
Carboxyvinyl polymer 0.4
Dextrin palmitate 0.3
Hydroxypropyl methylcellulose 0.2
Potassium hydroxide 0.1
Hydrogenated soybean phospholipid 0.05
Sodium edetate 0.02
Sodium polyacrylate 0.01
Purified water
100%

Example 4 (skin lotion)
γ-tocopherol 0.1
Ethanol 10.0
1,3-butylene glycol 2.0
Glycerin 1.0
Lactic acid 1.0
POE-hardened castor oil 60 1.0
Sodium alginate 0.1
Purified water
100%

Example 5 (pack)
δ-tocopherol 1.0
Polyvinyl alcohol 10.0
Ethanol 8.0
Glycerin 3.0
Polyethylene glycol 0.4
Fragrance 0.2
Methylparaben 0.1
Purified water
100%

Example 5 (milky lotion)
δ-tocopherol 0.1
1,3-butylene glycol 3.0
POE (2) oleyl ether 2.8
Sorbitan sesquioleate 2.2
Squalane 2.0
Octyl isononanoate 1.0
Phenoxyethanol 0.2
Butylparaben 0.1
Methylparaben 0.1
Carboxyvinyl polymer 0.1
Potassium hydroxide 0.1
Edetate trisodium 0.1
Purified water
100%

Example 5 (bathing agent)
γ-Tocopherol 2.0
POE (30) sorbitan tetraoleate 14.0
Olive oil 10.0
Jojoba oil 10.0
Squalane 8.0
POE (2) oleyl ether 3.0
Sorbitan sesquioleate 3.0
Butylparaben 0.2
Liquid paraffin
100%

Example 6 (cream)
δ-tocopherol 4.0
γ-tocopherol 1.0
Pyridoxine hydrochloride 0.1
Retinol 0.01
White petrolatum 25.0
Stearyl alcohol 10.0
Propylene glycol 5.0
Behenyl alcohol 5.0
POE-hardened castor oil 60 4.0
Glycerol monostearate 1.0
Methylparaben 0.1
Propylparaben 0.1
Dibutylhydroxytoluene 0.01
Purified water
100%

Example 6 (sunscreen)
δ-Tocopherol 2.0
Glyceryl tri-2-ethylhexanoate 10.0
Liquid paraffin 8.0
Glycerin 5.0
Olive oil 5.0
2-Ethylhexyl paramethoxycinnamate 5.0
Oxybenzone 4.0
Triethanolamine 0.5
Acrylic acid / alkyl methacrylate copolymer 0.4
Carboxyvinyl polymer 0.2
Phenoxyethanol 0.2
Purified water
100%

Claims (2)

A glutathione production promoter containing γ-tocopherol or δ-tocopherol. A skin external preparation containing the glutathione production promoter according to claim 1.