JP2000256131A - Tyrosinase production inhibitor and skin lotion containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a tyrosinase production inhibitor and a skin preparation for external use exhibiting extremely high bleaching effect. SOLUTION: This tyrosinase production inhibitor comprises an extract of wheat seed. An extract of wheat seed embryo bud part is preferable as the extract of wheat seed. This skin lotion comprises the tyrosinase production inhibitor. One or two or more kinds of medicinal agents selected from glabridin, glabrene, liquilitin, isoliquilitin and licorice extract containing these substances, coix seed extract, tea extract, scutellaria root extract, barley extract, fermentation metabolite, vitamin A and its derivative, vitamin C and its derivative, vitamin E and its derivative, ultraviolet light protecting agent, α-hydroxy acid and its salt and glycyrrhizic acid and glycyrrhetic acid and their derivatives may further be formulated in the skin lotion.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a tyrosinase production inhibitor and an external preparation for skin having a whitening effect containing the same.

[0002]

BACKGROUND OF THE INVENTION Melanin present in the skin is one of the factors that determine skin color and plays a role in protecting it from ultraviolet rays and is an important factor in cosmetics. The production of melanin is assumed to proceed by the action of tyrosinase, and may cause spots and freckles. Therefore, conventionally, attention has been paid to tyrosinase, an enzyme involved in melanin production, and the activity and action of tyrosinase are inhibited to reduce the amount of melanin produced in the skin, thereby causing darkening of the skin caused by sunburn and the like, and pigmentation. Vitamin C, glutathione, cysteine, and the like have been used as whitening agents to prevent phenomena such as spots, freckles, and the like caused by the above.

[0003] In addition, it is known that plant extracts such as sow scab extract have a whitening effect, but these are also studied from the viewpoint of inhibiting the activity of tyrosinase. On the other hand, there is little known about a whitening agent that suppresses the production of the enzyme tyrosinase itself to reduce the amount of melanin produced in the skin, and it has been reported that acetic acid, lactic acid and pyruvic acid have an effect of inhibiting tyrosinase production. Although there is a method (JP-A-1-305025), no plant extract having an effect was found. An object of the present invention is to provide a plant extract having an action of suppressing the production of tyrosinase itself.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies on various plant extracts as to whether or not they have an effect of suppressing tyrosinase production itself. As a result, it was found that the wheat seed extract has an effect of inhibiting tyrosinase production. And completed the present invention. That is, the present invention is a tyrosinase production inhibitor comprising a wheat seed extract. The wheat seed extract is preferably a wheat seed germ extract. The present invention is also an external preparation for skin, comprising the tyrosinase production inhibitor as an active ingredient.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Wheat seed extract, which is a tyrosinase production inhibitor of the present invention, comprises Triticum aestivum Linne (Gr.
amineae), Triticum sativum Lamarck or Triticum v
Extracted from ulgare Lamarck seeds using an extraction solvent. The whole wheat seed can be used for this extraction. More preferably, it is a germ part of a wheat seed.
The extraction method is not particularly limited, but the extraction is performed at low temperature or at room temperature to heating using various suitable solvents. It is preferable to extract the wheat seed or the germ after the pulverization. Further, a process such as pulverization and hydrolysis may be performed, and then an extraction process may be performed.

As the extraction solvent, for example, water or one or more of lower monohydric alcohols such as methyl alcohol and ethyl alcohol and liquid polyhydric alcohols such as glycerin, propylene glycol and 1,3-butylene glycol are used. be able to. The extract may be used as it is, or may be used after dilution or concentration. Also, the extract is filtered or adsorbed using ion exchange resin,
It may be purified by decolorization or deodorization. It can be used in the form of a solution, a paste, a gel, a powder, or the like. As an example of a preferable extraction method, a method of extracting with purified water at room temperature to low temperature for 1 to 5 days and then filtering is used.

[0007] The above-mentioned wheat seed extract has an action of suppressing tyrosinase production in melanocytes. Therefore, the presence of the wheat seed extract reduces the amount of melanin produced, and can prevent skin blackening caused by sunburn or the like, and phenomena such as spots and freckles caused by pigmentation. The wheat seed extract also contains glutathione. Glutathione also has the effect of reducing the melanin pigment and making the pigment thinner. From this point, the wheat seed extract can be expected to have a whitening effect.

An external preparation for skin is prepared by incorporating a tyrosinase production inhibitor comprising the wheat seed extract of the present invention as an active ingredient. This external preparation for skin is prepared by combining the extract obtained as described above as it is, or after purifying or diluting it as necessary, with a suitable cosmetic or pharmaceutical carrier. This external preparation for skin has a whitening effect. When the tyrosinase production inhibitor of the present invention is incorporated into an external preparation for skin, the form is not particularly limited, and for example, skin care cosmetics such as emulsions, creams, lotions, packs, cleansers, makeup cosmetics such as lipsticks and foundations. Cosmetics such as ingredients, ointments, dispersions, creams, pharmaceuticals such as external preparations, etc., and there is no particular limitation on the form thereof, solid form, paste form, mousse form,
Gel, powder, solution, solubilizing, emulsifying, powder dispersing and multi-layered can be used.

[0009] The amount of the wheat seed extract, which is a tyrosinase production inhibitor, incorporated into an external preparation for skin is preferably 0.00001 to 10% by weight (hereinafter simply referred to as "%") as a dry solid content, more preferably 0%. 0.0001 to 5%. Within this range, the wheat seed extract, which is an active ingredient, can be stably compounded, and a high whitening effect can be exhibited. When an extract is used, the concentration of the extract is not limited at all, as long as the content of dry solids as a solute is within the above range.

The whitening effect can be synergistically enhanced by further blending various medicinal agents with an external preparation for skin containing the wheat seed extract as the tyrosinase production inhibitor of the present invention. As the medicinal agent, glabridine, glabrene, liquiritin, isoliquiritin and liquorice extract containing these, liquorinin extract, tea extract, ogre extract, barley extract, fermentation metabolite, vitamin A
And derivatives thereof, vitamin C and derivatives thereof, vitamin E and derivatives thereof, ultraviolet ray protective agents, α-hydroxy acids and salts thereof and derivatives thereof, glycyrrhizic acid and derivatives thereof, and glycyrrhetinic acid and derivatives thereof. Two or more are used.

Examples of the above tea extract include extracts of green tea, black tea, oolong tea and the like. Examples of the fermentation metabolite include fermentation metabolites obtained from lactic acid bacteria, bifidobacteria, and the like. Examples of vitamin A and its derivatives include retinol and its derivatives (retinol palmitate, retinol acetate, etc.), retinal and its derivatives,
Carotenoids such as dehydroretinal and beta-carotene;

The above-mentioned vitamin C and its derivatives include L-ascorbic acid, L-ascorbyl palmitate, L-ascorbyl dipalmitate, L-ascorbyl isopalmitate, L-ascorbyl diisopalmitate, and tetraisopalmitate. L-ascorbyl, L-ascorbyl stearate, L-ascorbyl distearate, L-ascorbyl isostearate, L-ascorbyl diisostearate, L-ascorbyl myristate, L-ascorbyl dimyristate, L-ascorbyl isomyristate, diiso L-ascorbyl myristate, L-ascorbyl oleate, L-ascorbyl dioleate, L-ascorbyl 2-ethylhexanoate, sodium phosphate L-ascorbate,
Potassium L-ascorbate, magnesium L-ascorbate, calcium L-ascorbate, aluminum L-ascorbate, sodium L-ascorbate, sodium L-ascorbate Potassium, magnesium L-ascorbate sulfate, calcium L-ascorbate sulfate, L-
Aluminum ascorbate sulfate, sodium L-ascorbate, potassium L-ascorbate, L
-Magnesium ascorbate, calcium L-ascorbate, aluminum L-ascorbate and the like.

The above-mentioned vitamin E and its derivatives include tocopherol and its derivatives (dl-α (β, γ)-
Tocopherol, dl-α-tocopherol acetate, nicotinic acid-dl-α-tocopherol, linoleic acid-dl
-Α-tocopherol, dl-α-tocopherol succinate, etc.), ubiquinones and the like.

Examples of the above-mentioned ultraviolet ray protective agents include cinnamic acid-based ultraviolet absorbers such as 2-methoxyhexyl paramethoxycinnamate, 2-hydroxy-4-methoxybenzophenone, and 2-hydroxy-4-methoxybenzophenone-5.
Benzophenone ultraviolet absorbers such as sulfuric acid, 2-hydroxy-4-methoxybenzophenone-5-sodium sulfate, paraaminobenzoic acid, ethyl paraaminobenzoate,
Benzoic acid ultraviolet absorbers such as 2-ethylhexyl paradimethylaminobenzoate and amyl paraaminobenzoate,
Salicylic acid ultraviolet absorbers such as 2-ethylhexyl salicylate, homomenthyl salicylate, methyl salicylate, ethylene glycol salicylate, phenyl salicylate, amyl salicylate, and dibenzoylmethane ultraviolet absorbers such as 4-t-butyl-4'-methoxydibenzoylmethane Agents, urocanic acid-based ultraviolet absorbers such as ethyl urocanate, and ultraviolet scattering agents such as titanium oxide, zirconium oxide, and cerium oxide.

The above-mentioned α-hydroxy acids and salts thereof and derivatives thereof include lactic acid, sodium lactate, citric acid, sodium citrate, malic acid, sodium malate, tartaric acid, potassium sodium tartrate, glycolic acid and the like. . Glycyrrhizic acid and its derivatives,
Examples of glycyrrhetinic acid and its derivatives include glycyrrhizic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, β-glycyrrhetic acid, stearyl glycyrrhetinate, and disodium 3-succinyloxyglycyrrhetinate.

The content of the above-mentioned medicinal agent in the external preparation for skin of the present invention is preferably 0.0001 to 10%, more preferably 0.001 to 5%. When a plant extract or the like is used as it is as an extract, there is no problem as long as the dry solid content is within this range. Within this range, a skin external preparation having a more excellent tyrosinase production inhibitory effect, a high whitening effect, and a good feeling upon use can be obtained. In addition, these medicinal agents can be used alone or in combination of two or more.

The external preparation for skin of the present invention, which does not impair the effects of the present invention, contains components other than the above-mentioned components, and is usually used in the preparation of cosmetics, quasi-drugs, and external medicines. Ingredients: water (purified water, hot spring water, deep water, etc.),
Oils, surfactants, metal soaps, gelling agents, powders, alcohols, water-soluble polymers, film-forming agents, antibacterial agents, PH
Regulators, fresheners, blood circulation promoters, astringents, antiseborrheic agents, enzymes, whitening agents, active oxygen scavengers, anti-inflammatory agents, chelating agents,
One or more cell activators, moisturizers, extracts from animals and microorganisms, plant extracts, hormones, vitamins, resins, clathrates, fragrances, deodorants, salts, keratolytic agents, etc. can do.

The oil agent may be of any type, such as natural oil, synthetic oil, solid, semi-solid or liquid, as long as it is used in ordinary cosmetics. ,
Any oil agent such as hydrocarbons, waxes, fatty acids, higher alcohols, ester oils, silicone oils, and fluorine-based oils can be used. For example, hydrocarbons such as squalane, petrolatum, olive oil, castor oil, jojoba oil, mink oil, macadamian nut oil, apricot oil, persic oil, safflower oil, sunflower oil, avocado oil, medouhome oil, camellia oil, almond Oils, sesame oil, borage oil, cocoa butter, shea butter and other plant and animal-derived fats, beeswax, carnauba wax, candelilla wax,
By adding waxes such as gay wax, an emollient feeling is imparted and a skin external preparation having a good feel is obtained.
As the surfactant, any of anionic, cationic, nonionic and amphoteric surfactants can be used as long as they are used in ordinary cosmetics.

Examples of the metal soap include aluminum 12-hydroxystearate, zinc stearate, aluminum stearate, calcium stearate, magnesium stearate, zinc myristate, magnesium myristate, zinc cetyl phosphate, calcium cetyl phosphate, sodium zinc cetyl phosphate, Zinc laurate,
And zinc undecylenate.

As the gelling agent, N-lauroyl-L-
Amino acid derivatives such as glutamic acid and α, γ-di-n-butylamine; dextrin fatty acid esters such as dextrin palmitate, dextrin stearate, dextrin 2-ethylhexanoate palmitate, sucrose palmitate, and sucrose stearin Sucrose fatty acid esters such as acid esters; benzylidene derivatives of sorbitol such as monobenzylidene sorbitol and dibenzylidene sorbitol; and organically modified clay minerals such as dimethylbenzyl dodecyl ammonium montmorillonite clay and dimethyl dioctadecyl ammonium montmorillonite clay.

As the powder, if it is used in ordinary cosmetics, its shape (spherical shape, needle shape, plate shape, etc.), particle size (fog shape, fine particles, pigment grade, etc.), particle structure Regardless of whether it is porous or nonporous, any of organic powders and inorganic powders can be used. These powders may be compounded or surface-treated with an oil agent, silicone, or a fluorine compound. Examples of alcohols include lower alcohols such as ethanol and isopropanol, and polyhydric alcohols such as glycerin, diglycerin, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, and polyethylene glycol. Is mentioned.

As the water-soluble polymer, those used in ordinary cosmetics are used, for example, agar, alge colloid,
Guar gum, carrageenan, plant polymers such as locust bean gum, microbial polymers such as xanthan gum, dextran, pullulan, animal polymers such as casein, albumin, gelatin, starch, starch polymers such as carboxymethyl starch, Methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, cellulose-based cellulosic polymer, alginic acid-based polymer, polyvinyl methyl ether,
Vinyl polymers such as carboxyvinyl polymer and alkyl-modified carboxyvinyl polymer, polyoxyethylene polymers, polyoxyethylene polyoxypropylene copolymer polymers, acrylic polymers such as sodium polyacrylate and polyacrylamide, polyethylene There are inorganic water-soluble polymers such as imine, cationic polymer, bentonite, laponite, and hectorite. Further, a film forming agent such as polyvinyl alcohol and polyvinyl pyrrolidone is also included. By adding a water-soluble polymer,
It is possible to obtain a skin external preparation having a good feeling in use, in which moisture is prevented from evaporating from the skin due to the ability to form a film or moisture retention due to the ability to retain moisture.

Antibacterial agents include benzoic acid, sodium benzoate, carboxylic acid, sorbic acid, potassium sorbate, paraoxybenzoate, parachloromethcresol, hexachlorophene, benzalkonium chloride, chlorhexidine chloride, trichlorocarbanilide, Photosensitizer,
Bis (2-pyridylthio-1-oxide) zinc, phenoxyethanol, thianthol, isopropylmethylphenol and the like can be mentioned. Examples of the pH adjuster include potassium carbonate, sodium hydrogen carbonate, and ammonium hydrogen carbonate, and examples of the cooler include L-menthol and camphor.

Examples of the blood circulation promoting agent include nonylate valenylamide, capsaicin, zingerone, canthari tincture,
Ictamol, α-borneol, inositol hexanicotinate, cyclanderate, cinnarizine, tolazoline, acetylcholine, verapamil, γ-oryzanol and the like. Examples of the skin astringent include tannic acid and the like, examples of the antiseborrhea include thiantrol, and examples of the enzyme include lipase and papain. As a whitening agent,
Cysteine and its derivatives and salts thereof, hydroquinone and its derivatives, resorcin and its derivatives, glutathione and the like can be mentioned.

Examples of the active oxygen removing agent include superoxide dismutase, mannitol, hydroquinone,
Bilirubin, cholesterol, tryptophan, histidine, quercetin, quercitrin, catechin, catechin derivatives, rutin, rutin derivatives, taurine, thiotaurine, gallic acid, gallic acid derivatives, thiamines (thiamine hydrochloride, thiamine sulfate), riboflavins (riboflavin) , Riboflavin acetate, etc.), pyridoxines (pyridoxine hydrochloride, pyridoxine dioctanoate, etc.),
Vitamin B such as flavin adenine nucleotide, cyanocobalamin, folate, nicotinic acid (nicotinamide, benzyl nicotinate), choline; vitamin D such as ergocalciferol, cholecalciferol, dihydroxystanal; dibutylhydroxytoluene And butylhydroxyanisole.

Examples of anti-inflammatory agents include mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene, D-panthenol and their derivatives and salts thereof, ε-aminocaproic acid, diclofenac sodium, tranexamic acid and the like. Is mentioned. As chelating agents, gluconic acid, phytic acid and derivatives thereof and their salts, sodium polyphosphate, sodium metaphosphate, sodium hexametaphosphate, desferrioxamine, ethylenediaminetetraacetic acid and its salts, diethylenetriaminepentaacetic acid and its salts , O-phenanthroline, transferrin, ferritin, lactoferrin,
Caffeic acid, maltol, purpurogallin,
Pyrogallol and the like.

Examples of the cell activator include deoxyribonucleic acid and salts thereof, adenosine triphosphate, adenosine diphosphate,
Adenylic acid derivatives such as adenosine monophosphate and their salts, ribonucleic acids and their salts, cyclic AMP, cyclic GMP, flavin adenine nucleotide, guanine, adenine, cytosine, thymine, xanthine and their derivatives caffeine, Nucleic acid-related substances selected from theophylline and salts thereof, α- and γ-linolenic acid, eicosapentaenoic acid and derivatives thereof, estradiol, ethenylestradiol, succinic acid,
Examples thereof include organic acids such as salicylic acid and derivatives thereof, and salts thereof.

Examples of the humectant include mucopolysaccharides such as hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin and keratan sulfate or salts thereof, proteins such as collagen, elastin, fibronectin, keratin and derivatives thereof, and hydrolysates. Degradation products and their salts, glycine, alanine, valine, isoleucine,
Serine, threonine, aspartic acid, glutamic acid,
Asparagine, glutamine, lysine, hydroxylysine, arginine, cysteine, cystine, methionine,
Amino acid derivatives such as phenylalanine, tyrosine, proline, theanine, hydroxyproline, ortinine, citrulline, pyrrolidonecarboxylic acid or salts thereof, sorbitol, erythritol, maltose, maltitol, xylitol, xylose, trehalose, inositol, glucose, pentaerythritol, fructose, Examples include sucrose and its esters, dextrin and its derivatives, sugars such as honey, mucin, urea, phospholipids, glycolipids, ceramides and the like. By adding a humectant, a skin roughening effect and a moisturizing effect are imparted, and a skin external preparation having a good feeling in use can be obtained.

As the extract derived from animals or microorganisms, conventionally used extracts are used. Egg components such as calf blood extract, serum deproteinized extract, placenta extract, spleen extract, birds, etc., eggshell Membrane extract, cockscomb extract, shellfish extract, shellfish extract, royal jelly, silk protein and its degradation products or their derivatives, hemoglobin or its degradation products,
Lactoferrin or its degradation product, mollusc extract such as squid, fish meat extract, etc., mammals, birds, shellfish, insects,
Examples include extracts derived from animals such as fish, molluscs, and crustaceans, and extracts derived from microorganisms such as yeast extract and Reishi extract. By blending an animal or microorganism derived extract, moisturizing effect, cell activation effect, whitening effect, anti-inflammatory effect,
An effect of preventing skin aging, an effect of removing active oxygen, an effect of promoting blood circulation, and the like can be provided.

As the plant extract, a conventionally known plant extract is used, and there are no particular restrictions on the site of extraction of the plant, the extraction method, and the like. For example, the whole plant of the plant, or the roots, stems, stems, bark, and germs , Leaves, flowers, fruits, seeds, etc., which can be dried, shredded, squeezed, or subjected to appropriate treatment such as fermentation, using various suitable solvents at low temperatures or at room temperature to under heating. Can be extracted. Examples of the extraction solvent include water, lower monohydric alcohols such as methyl alcohol and ethyl alcohol, glycerin, propylene glycol,
1 such as liquid polyhydric alcohol such as 3-butylene glycol
Species or two or more can be used. Extraction can also be performed using a lipophilic solvent such as hexane, acetone, ethyl acetate, or ether, or other extraction using an oily component such as squalane. The obtained extract is used as it is, after filtration, or after adsorption, decolorization, deodorization and purification using an ion exchange resin. Pastes, gels, and powders can also be used.

Plants used for the above extraction include bukuro, carrot, panax ginseng, altea, arnica, aloe (curacao aloe, aloe vera), nettle, fennel, witch hazel (hamamelis), turmeric, yellowfin (oubak), hypericum, Rice (rice), Ibukitranoo, chamomile, Kawamuragi (Inchinko), Kiwi, Cucumber, Honeysuckle (Kinginka), Clara (Kudin), Gennoshoko, Grapes, Gardenia, Watercress (Netherlands), Comfrey (Hirakurisou), Sabonsou, Cactus , Hawthorn, georgia, perilla, peonies, birch, horsetail, bodaiju, salvia (sage), assembly, senkyu, mulberry (sohakuhiku), soybean, sashimi (thyme), touki, tokinsen , Houttuynia, jujube (gymnastics), elderberry, parsley, Butchers Broom,
Loofah, cattail (gourd), hop, marronnier, melissa, peach, saxifrage, raspberry, lavender, vetch, rose, neubara (agetsu), rosemary (mannenrou), lily, ashitaba, apricot (kyonin),
Oats, corn, mallow (Ocephaliaceae), purple (Sicon).

Further, pepper, ginger, lettuce, lemon, quince, orange, strawberry, safflower, beech,
Gentian, gentian (ryutan), mint, green mint (spearmint), mint (peppermint), mukuroji, eucalyptus, usbenioi, kumazasa, usubasaishin, keirinsaishin, odorikosou, burdock, garlic, hauchiwaame, carob, pineapple, porpoise Waremokou (Jiyu), Kobotuzuru, Shimotsuke, Avocado, Eucalyptus, Kaisou (Kombu, Macomb, Wakame, Hijiki, Hibamata, Umiuchiwa, Matsumo, Mozuku, Ishige, Habanori,
Brown algae such as kelp mushrooms, fukuronori, iwahige, kagomenori, swordfish, sujime, trolocomb, kajime, tsuruarame, chigaiso, shiroishige, lappamoku, hondawara, oobamoku, giant kelp, etc .;
Tsunomata, Tochiyaka, Suginori, Shikinori, Kainori, Usubanori, Ushikenori, Asakusanori, Fusanori, Kaginori, Hibiraudo, Catanori, Mukadenori, Matsunori, Tosakamatsu, Funori, Ibaranori, Ogonori,
Red algae such as sponge, darus, igis, egonori, konohanori and himegotake; chlorella, aonori, donariella, chlorococcus, anaoasa, kawanori, marimo, shiogusa, casa nori, phtojuzmo, tamazumo, honeyagusa, and aomyida, aomori aomori, etc. ).

Furthermore, grapefruit, prune, lime, genoshoko, shiitake mushroom, ononis, tormentilla, yuzu (pheasant), uren, hinoki, button (buttonpi), obajanohige (bakkumondou), sunflower, macadamia nut, almond, sesame, asparagus, Akane, red grape, red oak wrinkle, akebi, asa, morning glory, adzuki bean, asenyaku, amacha, amachaworu, knotweed, fig, ginkgo, ylang ylang, moray eel, ume, uwaurushi, unshiu mikan, elephantwort, ebisugusa, euphorbia, pea, pterodactyla Oguruma, Onigurumi, Ominaeshi,
Dutch strawberries, oysters, oysters, cashews, cashews, valerian, crows, karlin, guarana, kikyo, chrysanthemums, catalpa, crows, gimnema sylvesta, goldfish, guava, wolfberry, kudzu, camphor tree, chestnuts, cricket, keikei, keigo, keigogo , Pepper, coffee, sesame seeds, colombo, sasanqua, sansho, saffron, sakura.

Further, pomegranate, sands con, sampens,
Zion, Shobu, Watermelon, Stevia, Plum, Pear pear, Pear, Yarrow, Yarrow, Horseradish, Sekisho, Seri, Senega, Senna, Daio, Daidai, Tamarind, Taranoki, Dandelion, Chicory, Butterfly, Chocolate
Chorei, thrush, primrose, communis, luna,
Teuchigurumi, Tougan, Eucommia, Troloa mallow, Nazuna, Natsumikan, Nanten, Nigaki, Yarrow,
Pineapple, hibiscus, papaya, basil, lotus, spiderwort, hyopus goose, peanut, hikikoshi, hishi, pistachio, hiba, himematsutake, juniper, loquat, dandelion poppo, fushinoki, fujibakama, blueberry, boufu, bonsai, honoki, honoki
Ephedra, mango, mannentake, mishimasaiko, misohagi, honeysuckle, mimosa, melilot, melon, magnolia, momordica grosvenori, sprouts, yakuchi,
Yakumosou, cornflower, palm, yashazitsu, mistletoe, willowbird, pokeweed, bayberry, yuzuuriha, mugwort, rye, orchid, longan, apple, reishi,
Forsythia and the like (in the parentheses, other names of plants, names of crude drugs and the like are described). By blending the plant extract, a moisturizing effect, a cell activating effect, a whitening effect, an anti-inflammatory effect, a skin aging preventing effect, an active oxygen removing effect, a blood circulation promoting effect, and the like can be imparted.

As vitamins, vitamin Ks such as phytonadione, menaquinone, menadione and menadiol;
Vitamin Ps such as eriocitrin and hesperidin, biotin, carcinine, ferulic acid, and the like.

[0036]

EXAMPLES Next, the present invention will be described in more detail with reference to Reference Examples, Test Examples and Examples, but the present invention is not limited thereto.

Reference Example 1 Production of Wheat Seed Extract Seed 10 of wheat Triticum aestivum Linne (Gramineae)
100 g of ethanol having a concentration of 50% was added to the g, and the mixture was extracted for 3 days with occasional stirring at room temperature, followed by filtration to obtain a wheat seed extract. The dry solids content of this extract was 3%.

Reference Example 2 Production of Wheat Seed Extract Wheat Triticum aestivum Linne seeds crushed 1
100 ml of purified water was added to 0 g, extracted for 3 days with occasional stirring at room temperature, and filtered to obtain a wheat seed extract. The dry solids content of this extract was 5%.

Reference Example 3 Production of Wheat Seed Extract Pulverized seeds of wheat Triticum aestivum Linne 1
100 g of purified water was added to 0 g of the hydrolyzed and dried product, extracted for 3 days at room temperature with occasional stirring, and filtered to obtain a wheat seed extract. The dry solids content of this extract is 8%
Met.

Reference Example 4 Preparation of Wheat Seed Germ Extract Extract 10 g of wheat Triticum aestivum Linne germ was purified water 1
After adding 00 ml, the mixture was extracted for 3 days with occasional stirring at room temperature, and filtered to obtain a wheat seed germ extract. The dry solids content of this extract was 4%.

REFERENCE EXAMPLE 5 Production of Plant Extract To 10 g of each of Sophoraceae (JP) and Kujin (Clara) (JP), 100 ml of 70% (v / v) ethyl alcohol was added, and the mixture was stirred occasionally at room temperature. Extracted for 3 days and filtered to obtain each plant extract. The dry solids content of this extract was 1.8% for the extract of somaria and 2.8% for the extract of jinjin.

Test Example 1 Tyrosinase Production Inhibition Test 1 × 10 ⁵ B16 melanoma cells derived from mice were
The cells are seeded in a Petri dish containing an Eagle MEM medium containing v / v% fetal bovine serum, and allowed to stand at 37 ° C. in a carbon dioxide concentration of 5%. On the next day, a sample solution prepared so that the final concentration of each sample obtained in Reference Examples 1 to 5 is 0.5 μg / ml, is added and mixed. On the 5th day of the culture, the medium was replaced, and the sample solution was added again, followed by another 1-day culture. Extraction of RNA and examination of tyrosinase expression level were performed according to the RNA extraction method and Northern blotting method described in “Cell Engineering Experiment Protocol”, pp. 31-33 and 149-151 (published by Shujunsha). The densities were compared with a densitometer. By this method, the tyrosinase expression level (A) and the control tyrosinase expression level (B) for each sample concentration were calculated from the control tyrosinase expression level, and the tyrosinase production inhibition rate was calculated by the following equation. Table 1 shows the above results. Tyrosinase production inhibition rate = (1-A / B) × 100

[0043]

[Table 1]

As is evident from Table 1, the wheat seed extract and the wheat seed germ part extract exhibited a higher tyrosinase production inhibitory effect than other plant extracts.

Test Example 2 Test for Inhibition of Melanin Production by Cultured Cells 1 × 10 ⁵ mouse-derived B16 melanoma cells were
The cells are seeded in a Petri dish containing an Eagle MEM medium containing v / v% fetal bovine serum, and allowed to stand at 37 ° C. in a carbon dioxide concentration of 5%. On the next day, a sample solution prepared so that the final concentration of each sample obtained in Reference Examples 1 to 5 is 0.5 μg / ml, is added and mixed. On the fifth day of the culture, the medium is replaced, and the sample solution is added again. The next day, the medium is removed, the cells are detached with a solution containing trypsin and EDTA, and the cells are collected. Melanin was extracted from the collected cells by treatment with trichloroacetic acid, ethanol and ether, dissolved in a dilute alkaline solution, and the absorbance at 400 nm was measured. The amount of melanin was determined from the calibration curve of the melanin reagent. By this method, the amount of melanin (A) and the amount of melanin (B) of the control relative to each sample concentration were calculated from the amount of melanin of the control, and the melanin production inhibition rate was calculated by the following equation. Table 2 shows the above results. Melanin production inhibition rate = (1-A / B) × 100

[0046]

[Table 2]

As is evident from Table 2, the wheat seed extract and the wheat seed germ extract exhibited a higher inhibitory effect on melanin production than other plant extracts.

Example 1 Cream A cream was prepared according to the composition shown in Table 3 and the following method, and its skin effect was examined. Table 3 also shows the results.

[0049]

[Table 3]

(Preparation method) A: Components (1) to (6), (11) and (12) are mixed and heated to 70 ° C. B: Components (9) and (14) are mixed and heated to 70 ° C. C: After B was added to A and mixed, (7), (8), (10) and (13) were added, and the mixture was cooled to obtain a cream.

(Test Method) 27 per test cream
A panel consisting of 15 women aged 54 to 54
After washing the face for 12 weeks, an appropriate amount of the test cream was applied to the face. The beautiful skin effect of the application was evaluated according to the following criteria.

(Evaluation Criteria) <Evaluation> <Contents> Effective The dullness of the skin became inconspicuous. Slightly effective Skin dullness became less noticeable. Ineffective No change from before use.

From the results in Table 3, it can be seen that the composition of the present invention containing the wheat seed extract represented by the present invention products 1 to 6 and a medicinal agent can be applied to the skin to give a "dullness" to the skin. It has been clarified that the occurrence of blemishes can be prevented and improved, and a beautiful skin can be obtained.

Example 2 Lotion (Formulation) (%) (1) Glycerin 5.0 (2) 1,3-butylene glycol 6.5 (3) Polyoxyethylene (20EO) Sorbitan 1.2 Monolaurin Acid ester (4) Ethyl alcohol 8.0 (5) Wheat seed extract * 1 10.0 (6) Red gourd extract * 2 1.0 (7) L-ascorbic acid sodium sulfate * 3 0.5 (8 ) Lactic acid 0.05 (9) Sodium lactate 0.1 (10) 2-Hydroxy-4-methoxybenzophenone-5-sulfuric acid * 4 3.0 (11) Preservative proper amount (12) Fragrance proper amount (13) Purified water residue Amount * 1 Manufactured in Reference Example 3 * 2 Ichimaru Falcos * 3 Sigma * 4 Merck

(Production method) A: Components (3), (4), (10), (11) and (12) are mixed and dissolved. B: Components (1), (2), (5) to (9) and (13) are mixed and dissolved. C: A and B were mixed and made uniform to obtain a lotion.

Example 3 Emulsion (Formulation) (%) (1) Polyoxyethylene (10EO) Sorbitan 1.0 Monostearate (2) Polyoxyethylene (60EO) Sorbit 0.5 Tetraole Ethate (3) Glyceryl monostearate 1.0 (4) Stearic acid 0.5 (5) Behenyl alcohol 0.5 (6) Squalane 8.0 (7) Retinol palmitate * 1 0.002 (8) Stearyl glycyrrhetinate * 2 0.3 (9) Wheat seed germ extract * 3 5.0 (10) Licorice extract * 4 0.1 (11) Oolong tea extract * 5 0.1 (12) Preservative 0.1 ( 13) Carboxyvinyl polymer 0.1 (14) Sodium hydroxide 0.05 (15) Ethyl alcohol 5.0 (16) Remaining purified water (17) Appropriate perfume * 1 day Roche * 2 Maruzen Pharmaceuticals Co., Ltd. * 3 those prepared in Reference Example 4 * 4 Maruzen Pharmaceuticals Co., Ltd. * 5 Maruzen Pharmaceuticals Co., Ltd.

(Preparation method) A: Components (13) to (16) are mixed by heating and maintained at 70 ° C. B: Components (1) to (8) and (12) are mixed by heating and maintained at 70 ° C. C: Add A to B, mix and emulsify uniformly. D: After cooling C, (9) to (11) and (17) were added and mixed uniformly to obtain an emulsion.

Example 4 Ointment (Formulation) (%) (1) Stearic acid 18.0 (2) Cetanol 4.0 (3) Acetic acid-dl-α-tocopherol * 1 0.3 (4) Dipotassium glycyrrhizinate * 2 0.5 (5) Triethanolamine 2.0 (6) Glycerin 5.0 (7) Wheat seed extract * 3 1.0 (8) Fermented metabolite of lactic acid bacteria * 4 1.0 (9) Purified water residue Amount * 1 Eisai * 2 Maruzen Pharmaceutical * 3 Manufactured in Reference Example 1 * 4 Ichimaru Falcos

(Preparation method) A: A part of the components (4), (5), (6) and (9) is mixed by heating and kept at 75 ° C. B: Components (1) to (3) are mixed by heating and kept at 75 ° C. C: A is gradually added to B. D: C was dissolved in the rest of (9) while cooling C (7), (8)
Was added to obtain an ointment.

Example 5 Pack (Formulation) (%) (1) Polyvinyl alcohol 20.0 (2) Ethyl alcohol 20.0 (3) Glycerin 5.0 (4) Kaolin 6.0 (5) Wheat seed extract * 1 0.005 (6) Barley extract * 2 0.2 (7) Yoquinin extract * 3 0.2 (8) Malic acid 0.05 (9) Preservative 0.2 (10) Flavor 0.1 (11) Remaining purified water * 1 Produced in Reference Example 3 * 2 manufactured by Technoble * 3 manufactured by Maruzen Pharmaceutical

(Production method) A: Components (1), (3), (4), (8) and (11) are mixed,
Heat to 70 ° C. and stir. B: Components (2), (9) and (10) are mixed. C: The above B was added to the above A, mixed, and then cooled (5)
To (7) were uniformly dispersed to obtain a pack.

Example 6 Detergent (Formulation) (%) (1) Stearic acid 10.0 (2) Palmitic acid 8.0 (3) Myristic acid 12.0 (4) Lauric acid 4.0 (5) Oleyl Alcohol 1.5 (6) purified lanolin 1.0 (7) flavor 0.1 (8) preservative 0.2 (9) glycerin 18.0 (10) citric acid 0.05 (11) calcium hydroxide 6. 0 (12) Wheat seed germ extract * 1 1.0 (13) Green tea extract * 2 0.05 (14) Yokuinin extract * 3 0.05 (15) Remaining purified water * 1 In Reference Example 4 Manufactured * 2 Maruzen Pharmaceutical * 3 Maruzen Pharmaceutical

(Production method) A: Components (9), (10), (11) and (15) were mixed, and
Heat to 0 ° C. B: Components (1) to (6) and (8) are mixed and heated to 70 ° C. C: The above B was added to the above A, kept at 70 ° C. for a while, cooled to 50 ° C. after the reaction was completed, and the components (7) and (12) to
(14) was added, and the mixture was cooled to obtain a washing agent.

Example 7 Gel Ointment (Formulation) (%) (1) Carboxyvinyl Polymer 1.0 (2) Triethanolamine 1.0 (3) 1,3 Butylene Glycol 10.0 (4) Wheat Seed Extract * 1 0.01 (5) Ogon extract * 2 0.02 (6) Remaining purified water * 1 Produced in Reference Example 2 * 2 Ichimaru Falcos

(Preparation method) A: Components (1) and (3) to (6) are mixed and dissolved. B: The component (2) was added to A, mixed and homogenized to obtain a gel ointment.

Example 8 Cream (Formulation) (%) (1) Polyoxyethylene (40EO) monostearate 2.0 (2) Glycerin monostearate (self-emulsifying type) 5.0 (3) Stearin Acid 5.0 (4) behenyl alcohol 0.5 (5) squalane 15.0 (6) cetyl isooctanoate 5.0 (7) preservative 0.1 (8) dl-α-tocopherol * 1 0.5 (9 ) Stearyl glycyrrhetinate * 2 0.2 (10) 1,3-butylene glycol 5.0 (11) Wheat seed extract * 3 0.2 (12) Sodium lactate * 4 0.1 (13) Purified water (14) Appropriate amount of flavor * 1 Eisai * 2 Maruzen Pharmaceutical * 3 Manufactured in Reference Example 3 * 4 Wako Pure Chemical

(Production method) A: Components (1) to (9) are heated and dissolved at 70 ° C. B: Heat components (10), (12) and (13) to 70 ° C. C: Add A to B and mix. D: Components (11) and (14) were added to C, and the mixture was cooled to obtain a cream.

Example 9 Liquid Foundation (Formulation) (%) (1) Lanolin 7.0 (2) Liquid Paraffin 2.0 (3) Stearic Acid 2.0 (4) Cetanol 1.0 (5) 4-t -Butyl-4'-methoxydibenzoylmethane * 1 3.0 (6) 2-Ethylhexyl paramethoxycinnamate * 2 5.0 (7) Glycerin 5.0 (8) Triethanolamine 1.0 (9 5.) Carboxymethylcellulose 0.7 (10) Remaining purified water (11) Mica 15.0 (12) Talc 6.0 (13) Titanium oxide 2.0 (14) Zinc oxide 3.0 (15) Color pigment 0 (16) Wheat seed extract * 3 0.1 (17) Yokuinin extract * 4 0.05 (18) Black tea extract * 5 0.05 (19) Appropriate amount of fragrance * 1 Givaudan * 2 BASF * 3 Manufactured in Reference Example 3 * 4 Maruzen Pharmaceutical Co., Ltd. * 5 Ichimaru Falcos Co., Ltd.

(Preparation method) A: Components (1) to (6) are mixed and heated to 70 ° C. B: Components (11) to (15) are added to A and mixed uniformly. C: Components (7) to (10) are uniformly dissolved and kept at 70 ° C. D: Add C to B and emulsify uniformly. E: After cooling D, components (16) to (19) were added to obtain a liquid foundation.

The lotion of Example 2, the emulsion of Example 3, the ointment of Example 4, the pack of Example 5, the cleaning agent of Example 6, the gel ointment of Example 7, the cream of Example 8, and the Example The liquid foundation 9 can be applied to the skin to prevent the occurrence of "dullness" on the skin and to improve pigmentation such as spots and freckles, making the skin beautiful and transparent. Was something.

[0071]

Industrial Applicability The tyrosinase production inhibitor of the present invention has an excellent tyrosinase production inhibitory action and, moreover, a melanin production inhibitory action. And an external preparation for skin containing this tyrosinase production inhibitor has a tyrosinase production inhibitory action,
Since it has a melanin production inhibitory effect, it is highly effective in inhibiting skin pigmentation, and is effective for skin whitening such as blackening of skin due to sunburn, prevention and improvement of spots and freckles, and improvement of dull skin. It is extremely useful in beauty and medicine. In addition, when the tyrosinase production inhibitor consisting of the wheat seed extract is combined with a specific medicinal agent and formulated into an external preparation for skin, the above effects are synergistically exerted.

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[Procedure amendment]

[Submission date] November 17, 1999 (1999.11.
17)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0046

[Correction method] Change

[Correction contents]

[0046]

[ Table 2 ]

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0049

[Correction method] Change

[Correction contents]

[0049]

[ Table 3 ]

[Procedure amendment 3]

[Document name to be amended] Statement

[Correction target item name] 0053

[Correction method] Change

[Correction contents]

From the results shown in Table 3, the composition of the invention 1 according to the invention was obtained.
The composition of the present invention, which comprises a product and a wheat seed extract represented by the present invention products 2 to 4 and a medicinal agent, prevents and improves the occurrence of "dullness" and the like on the skin by applying them to the skin. It was clear that the skin could be beautiful.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 7/00 A61K 7/00 U 7/48 7/48 7/50 7/50 A61P 17/00 31 / 00 617 A61K 35/78 35/78 U W (72) Inventor Shizuka Uehara 48-18 Sakaemachi, Kita-ku, Tokyo F-term (reference) 4C083 AA031 AA032 AA072 AA111 AA112 AB032 AB212 AB242 AB432 AB442 AC022 AC072 AC082 AC102 AC122 AC242 AC301 AC302 AC342 AC352 AC402 AC422 AC442 AC482 AC542 AC782 AD092 AD112 AD272 AD512 AD531 AD532 AD621 AD641 AD642 AD661 AD662 BB46 CC02 CC04 CC05 CC07 CC12 CC23 DD22 DD23 DD31 DD41 EE16 4C088 AB38 AB04 AB60 AB CA05 CA06 MA07 MA17 MA22 MA28 MA63 NA14 ZA89 ZC20

Claims (4)

[Claims] 1. A tyrosinase production inhibitor comprising a wheat seed extract. 2. The tyrosinase production inhibitor according to claim 1, wherein the wheat seed extract is a wheat seed germ part extract. 3. An external preparation for skin, comprising the tyrosinase production inhibitor according to claim 1 as an active ingredient. 4. Gravlidine, glabrene, liquiritin, isoliquiritin and liquorice extract, yoquinin extract, tea extract, gongo extract, barley extract, fermentation metabolite, vitamin A and its derivatives, vitamins containing them Contains one or more selected from C and its derivatives, vitamin E and its derivatives, UV protective agents, α-hydroxy acids and their salts and their derivatives, glycyrrhizic acid and its derivatives, and glycyrrhetinic acid and its derivatives The external preparation for skin according to claim 3, wherein the preparation is used.