JP5835894B2 - Tyrosinase activity inhibitor, melanin production inhibitor and whitening agent, and cosmetics, food and beverage compositions and pharmaceutical compositions containing them - Google Patents

Description

The present invention relates to a tyrosinase activity inhibitor, a melanin production inhibitor, and a whitening agent, and more specifically, it is excellent in preventing and treating skin spots, buckwheat and sunburn pigmentation caused by ultraviolet rays and the like, and is more stable than conventional ones. The present invention relates to a tyrosinase activity inhibitor, a melanin production inhibitor and a whitening agent. Moreover, it is related with the cosmetics, food-drinks composition, and pharmaceutical composition containing a tyrosinase activity inhibitor, a melanin production inhibitor, and a whitening agent.

Since skin is the outermost layer of the body, it is easily affected by environmental factors in daily life. Ultraviolet rays and the active oxygen and lipid peroxides that are generated by it cause inflammation and other tissues such as skin. Cause a lot of damage. Furthermore, pigment cells in the skin are activated by ultraviolet rays and inflammation caused by the ultraviolet rays, and the production of melanin in the cells is remarkably increased, and eventually causes skin pigmentation after spots, buckwheat and sunburn. This phenomenon is necessary for the living body to protect the skin and cells from ultraviolet rays and the like, but in recent years, it has been required to suppress melanin synthesis from a cosmetic viewpoint.

In general, melanin is formed in pigment cells by the action of tyrosinase, a melanin synthase, which changes from tyrosine to dopa, from dopa to dopaquinone, and then through an intermediate such as 5,6-dihydroxyindophenol. Has been. Therefore, in order to prevent and treat skin spots, buckwheat and sunburn pigmentation, it is conceivable to suppress melanin synthesis and to inhibit the activity of tyrosinase, which is a melanin synthase.

So far, substances capable of inhibiting the activity of tyrosinase have been proposed or used. Typical examples thereof include ascorbic acids, hydrogen peroxide, hydroquinone, catechol, sulfurs, kojic acid, arbutin, glutathione and the like (for example, see Patent Document 1 or 2). In addition, there are those composed of o-coumaric acid-β-D-glucoside (for example, see Patent Document 3) and those containing a calcined chestnut skin extract (for example, see Patent Document 4). .

On the other hand, arginyl fructosyl glucose has a vasodilatory effect, and it is known that arginyl fructosyl glucose can be produced by subjecting arginine and maltose to a Maillard reaction in the presence of an acid (see, for example, Patent Document 5). ing. In addition, maltulosyl arginine, which can be produced by Maillard reaction of arginine and maltose in the presence of acid, has anti-inflammatory action, TNF-α production inhibitory action, cyclooxygenase-2 activity inhibitory action, anti-aging action, type I collagen production It has been known to have a promoting action, a type IV collagen production promoting action, a transglutaminase-1 production promoting action, a hyaluronic acid production promoting action and a nitric oxide production promoting action (see, for example, Patent Document 6).

JP-A-10-182404 Japanese Patent Laid-Open No. 10-279460 Japanese Patent No. 2986262 JP 2007-126406 A JP-A-9-316091 JP 2010-90076 A

As in the background art described above, according to the conventional tyrosinase activity inhibitor, melanin production in cells is suppressed, and skin pigmentation including spots and the like can be alleviated. However, conventional tyrosinase activity inhibitors, such as ascorbic acid, have poor heat resistance and are likely to change over time, and a large amount of tyrosinase activity inhibitor may be required to obtain a sufficient effect. On the other hand, it has been known that arginyl fructosyl glucoses have a vasodilatory action as in Patent Document 5 and that maltulosylarginine has various actions as in Patent Document 6, It has not been known that tosylglucose has a tyrosinase activity inhibitory action, a melanin production inhibitory action and a whitening action.

The object of the present invention is to prevent and treat skin stains, buckwheat and sunburn pigmentation caused by aging and ultraviolet rays in daily life, and is a more stable tyrosinase activity inhibitor than conventional melanin It is in providing a production inhibitor and a whitening agent. In addition, it is a secondary object to provide a cosmetic, a food / beverage composition, and a pharmaceutical composition that are excellent in the effect of preventing and treating skin spots, buckwheat, and pigmentation after sunburn.

As a result of intensive studies in view of the above circumstances, the present inventors have found that arginyl fructosyl glucose has a tyrosinase activity inhibitory action, a melanin production inhibitory action, and a whitening action.

The present invention is a tyrosinase activity inhibitor containing arginyl fructosyl glucose as an active ingredient. It is a melanin production inhibitor containing arginyl fructosyl glucose as an active ingredient. A whitening agent containing arginyl fructosyl glucose as an active ingredient .

According to the present invention, tyrosinase activity inhibitor, melanin, which is excellent in the effect of preventing and treating skin spots, buckwheat and sunburn pigmentation caused by aging and ultraviolet rays in daily life, is more stable than conventional ones, A production inhibitor and a whitening agent can be provided. Moreover, the cosmetics, the food-drinks composition, and the pharmaceutical composition which are excellent in the effect which prevents and treats the skin spot, buckwheat, and the pigmentation after sunburn by containing these can be provided.

Hereinafter, the present invention will be described in detail.

Arginyl fructosyl glucose used in the present invention is a compound represented by the following general formula.

In the tyrosinase activity inhibitor, melanin production inhibitor and whitening agent of the present invention, the arginyl fructosyl glucose is used alone, and is usually used in cosmetics, food and beverage compositions or pharmaceutical compositions depending on the purpose. Ingredients that are permitted to be used or components that are allowed to be used can be appropriately blended within a range that does not impair the effects of the present invention. Examples of such components include various other whitening agents, antioxidants, cell activators, humectants, UV inhibitors, and the like, which can be used alone or in combination of two or more. The amount of arginyl fructosyl glucose in the tyrosinase activity inhibitor, melanin production inhibitor or whitening agent of the present invention, or in a cosmetic, food / beverage composition or pharmaceutical composition containing these is the tyrosinase activity inhibitor, melanin production 0.005% by mass (hereinafter abbreviated as wt%) or more in terms of dry solid content, based on the total amount of the inhibitor or whitening agent, or the cosmetic, food / beverage composition or pharmaceutical composition containing these. 10 wt% or less is preferable in view of the effect and cost. In particular, 0.005 wt% or more and 5 wt% or less is preferable when blended and applied to a product.

As a manufacturing method of arginyl fructosyl glucose used for this invention, it can manufacture by heating in presence of maltose and an acid using arginine, for example. Specifically, arginine and maltose are dissolved in an acid as a solvent and heated at 70 ° C. for 30 minutes. The reaction between arginine and maltose is from 1 to 1000 parts by weight, preferably from 50 to 300 parts by weight, based on 100 parts by weight of arginine. The solvent for the above reaction is preferably an organic acid, and examples thereof include acetic acid and butyric acid. Acetic acid is particularly preferable. In addition, when both substances are made to react in aqueous solution, efficiency will fall, Therefore It is preferable to use the acid which shows liquid state in anhydrous states, such as glacial acetic acid, as a solvent. As the temperature condition of the above reaction, it can be carried out at any temperature from room temperature to the boiling point, but a temperature condition of 60 to 80 ° C. is preferable from the viewpoint of reaction rate and efficiency. The reaction time varies depending on the temperature and the type of acid as a solvent, but is usually about 5 to 300 minutes, preferably 10 to 60 minutes. After the reaction, the insoluble substance is removed by filtration or centrifugation after cooling, and an acid as a reaction solvent is distilled off from the obtained filtrate or supernatant to obtain a mixture containing arginyl fructosyl glucose. it can.

When used in tyrosinase activity inhibitors, melanin production inhibitors or whitening agents, or in cosmetics, food and beverage compositions or pharmaceutical compositions containing these, it can be used as a mixture containing arginyl fructosyl glucose. If necessary, arginyl fructosyl glucose is purified from a mixture containing arginyl fructosyl glucose by a conventional method and used.

The purification method is not particularly limited, and can be performed by a conventional method. For example, the mixture obtained by distilling off the solvent is dissolved in 2 to 5 times the amount of water, and subjected to column chromatography using a cation exchange resin or the like to give about 2 to 6 times the volume of the cation exchange resin. After washing with water, arginyl fructosyl glucose can be obtained by eluting arginyl fructosyl glucose with 0.5 to 2% ammonia water of about 4 to 6 times the volume of the resin. Arginyl fructosyl glucose can be obtained by purifying the obtained arginyl fructosyl glucose fraction using any organic compound purification method such as size exclusion chromatography and reverse phase chromatography.

In the present invention, when a tyrosinase activity inhibitor, melanin production inhibitor or whitening agent containing arginyl fructosyl glucose as an active ingredient is added to a cosmetic, a food or beverage composition or a pharmaceutical composition, the tyrosinase activity inhibitor As other ingredients to be blended together with the melanin production inhibitor or the whitening agent, all of those that can be normally used in cosmetics, food and beverage compositions or pharmaceutical compositions can be used. It can be selected as appropriate.

In addition to tyrosinase activity inhibitors, melanin production inhibitors or whitening agents containing arginyl fructosyl glucose alone or a mixture containing arginyl fructosyl glucose as an active ingredient, the cosmetics of the present invention include, for example, generally cosmetics. Including excipients and flavors used, fats and oils, surfactants, moisturizers, whitening agents other than the whitening agent of the present invention, pH adjusters, binders, polyhydric alcohols, essential oils and perfumes , Thickeners, antiseptics, antioxidants other than the antioxidants of the present invention, UV absorbers, pigments, plant pulverized products and herbal medicines, inorganic salts and acids, various cosmetic ingredients such as detergents and emulsifiers Can be appropriately blended.

The fats and oils are generally used in cosmetics, for example, soybean oil, almond oil, paraffin, cetanol, avocado oil, olive oil, jojoba oil, coconut oil, palm oil, nuka oil, jojoba oil, egg yolk oil, castor oil. Vegetable oils such as squalane, avocado oil, lanolin, liquid paraffin, white petrolatum; animal fats such as beef tallow, pork fat, horse fat, turtle oil, mink oil, perserine oil, squalane; methylpolysiloxane, behenyl alcohol, tricaprin Examples thereof include synthetic fats and oils such as glyceryl acid, glyceryl trioctanoate, and liquid paraffin.

Examples of the surfactant include anionic surfactants such as sodium lauryl sulfate, triethanolamine lauryl sulfate, and diethanolamide lauric acid; cationic properties such as stearyltrimethylammonium chloride, cetyltrimethylammonium chloride, and benzalkonium chloride. Surfactant: Nonionic surfactants such as glyceryl monostearate, sorbitan monostearate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene hydrogenated castor oil, sucrose ester, fatty acid amide, etc. .

Examples of the humectant include synthetic humectants such as glycerin, propylene glycol, 1,3-butylene glycol, polyoxyglycerin (26E.O), pyrrolidone carboxylate soda, pantethein-S sulfonate; hyaluronic acid, elastin, Examples include natural humectants such as keratin, dermatan sulfate, collagen, placenta extract, royal jelly, microbial fermentation solution such as chitin, chitosan, pectin, and other plant and animal extracts.

Examples of the whitening agent other than the whitening agent of the present invention include placenta extract and other plant and animal extracts in addition to ascorbic acid, arbutin and derivatives thereof.

Examples of the pH adjuster include organic acids such as citric acid, lactic acid, salicylic acid, tartaric acid, malic acid, citric acid, benzoic acid, sodium citrate, fumaric acid, sodium monohydrogen phosphate, potassium dihydrogen phosphate, Examples include inorganic acids and salts thereof.

The binders are generally used in cosmetics, for example, sodium carboxymethylcellulose, methylcellulose, sodium salt, casein, pectin, starch, sodium alginate, polyvinyl alcohol, polyvinylpyrrolidone, locust bean gum, carrageenan, agar And carbopol.

Examples of the polyhydric alcohols include glycerin, propylene glycol, sorbitol, polyethylene glycol, and 1,3-butylene glycol.

The essential oils and perfumes include lavender oil, jasmine oil, rose oil, lemon oil, orange oil, peppermint oil, thyme oil, ginger oil, fennel oil, cedar oil, hiba oil, cypress oil, rose oil, eucalyptus oil, Examples include natural and synthetic fragrances such as camphor, peppermint oil, spearmint oil, geraniol, mandarin oil, spruce, citronellol.

Examples of the thickener include carboxymethylcellulose, carboxymethylcellulose Na, hydroxymethylcellulose, hydroxyethylcellulose, carboxyvinyl polymer, polyvinyl alcohol, sodium alginate, carrageenan, xanthan gum, bentonite and the like.

Examples of the preservative include paraoxybenzoic acid esters such as methyl paraben, ethyl paraben, propyl paraben, and butyl paraben, phenoxyethanol, ethanol, and dehydroacetic acid.

Examples of the antioxidant include alcorbic acid, EDTA4Na, EDTA2Na, and butyloxytoluene.

The ultraviolet absorber is not particularly limited as long as it has a property of selectively absorbing ultraviolet rays. For example, oxybenzone, oxybenzone sulfonic acid, tetrahydroxybenzophenone, sodium dihydroxydimethoxybenzophenone sulfonate, Examples include dihydroxydimethoxybenzophenone, dihydroxybenzophenone, sinoxate, methyl diisopropylcinnamate, octyl methoxycinnamate, glyceryl paraaminobenzoate, octyl paraaminobenzoate, and the like.

Examples of the pigment include bengara, yellow iron oxide, black iron oxide, titanium oxide, nylon powder, zinc oxide, sericite, mica, and talc.

Examples of plant pulverized products and herbal medicines include lemon peel, seaweed, cypress, hiba, fukkas, rice bran, shrimp, ginger, licorice, chimpi, spruce, yuzu, tokyo, carrot, mint, keihi, buckwheat, mugwort, Examples thereof include pulverized products such as dokudami, momonoha, chamomile, aloe, jasmine, rosehip, lavender, guava, ougon, wolfberry, litchi, elderberry, ashitaba, okogi, burdock, black sesame and black rice, and extracts thereof.

Examples of inorganic salts and acids include sodium chloride, sodium bicarbonate, sodium carbonate, boric acid, borax, sodium sulfate, sodium sulfide, potassium sulfide, sodium nitrate, calcium nitrate, ammonium sulfate, sodium thiosulfate, calcium hydrogen phosphate, chloride Examples include potassium, ammonium chloride, sodium phosphate, sodium hyposulfite, calcium thiosulfate, sulfur, sodium sesquicarbonate, magnesium sulfate, anhydrous silicic acid, metasilicic acid, and boric acid.

Examples of the detergent include fatty acid soaps, carboxylic acid type surfactants, alkyl sulfate ester type surfactants, sulfosuccinate type surfactants, taurates, acyl sarcosine, acyl-β-alanine acyls, etc. Amino acid type surfactants, anionic surfactants such as phosphate ester type surfactants, imidazoline type, alkylbetaine type, alkylamide betaine type, alkylsulfobetaine type amphoteric surfactants and alkyl saccharides, EO addition type Surfactant etc. are mentioned.

As the emulsifier, a substance known as a cosmetic raw material can be used. Particularly preferred are sucrose fatty acid esters such as sucrose laurate, sucrose myristate, sucrose palmitate, sucrose stearate, sucrose oleate, sucrose erucate, tetraglycerin mono Stearic acid ester, tetraglycerin monooleic acid ester, tetraglycerin tristearic acid ester, hexaglycerin monolauric acid ester, hexaglycerin monomyristic acid ester, hexaglycerin monostearic acid ester, hexaglycerin tristearic acid ester, decaglycerin monolauric acid ester , Decaglycerin monomyristic acid ester, decaglycerin monostearic acid ester, decaglycerin distearic acid ester, decaglycerin Tristearic acid ester, decaglycerin pentastearic acid ester, decaglycerin monoisostearic acid ester, decaglycerin diisostearic acid ester, decaglycerin pentaisostearic acid ester, decaglycerin monooleic acid ester, decaglycerin trioleic acid ester, decaglycerin pentaolein Polyglycerin fatty acid esters such as acid esters, sorbitan branched fatty acid esters such as sorbitan monoisostearate, sorbitan sesquiisostearate, sorbitan triisosteteate, soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, hydrogenated egg yolk lecithin, and these Of lysolecithin and / or hydrogenated lysolecithin, hydroxy Lecithins such as phased hydroxy lecithins, monoisostearate, glyceryl sesquiisostearate, glyceryl can be exemplified such as glycerin branched fatty acid esters such diisostearate glyceryl.

Furthermore, the cosmetic of the present invention includes, in addition to the above-mentioned ones, as necessary other components such as lactose, milk, condensed milk, titanium, talc and other inorganic pigments, isopropylmethylphenol, chlorohexidine hydrochloride, glucone Bactericides such as chlorohexidine acid, vitamins such as vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin P, CoQ10, CoQ9, CoQ8, fluidizing agents such as silicic acid anhydride and synthetic aluminum silicate, and pharmaceutical compositions, Quasi-drugs and cosmetic tar pigments can be appropriately blended together with tyrosinase activity inhibitor, melanin production inhibitor or whitening agent containing arginyl fructosyl glucose alone or a mixture containing arginyl fructosyl glucose as an active ingredient.

The form of the cosmetic of the present invention is not particularly limited, but for example, basic cosmetics such as creams, emulsions, lotions, essences, facial cleansers, cleansing agents, packs, makeup such as lipsticks, foundations, and eye colors. They can be used as cosmetics, body soaps, soaps, shampoos, rinses, toiletries such as conditioners, and hair cosmetics such as hair setting agents.

It does not specifically limit as a form of the food-drinks composition of this invention, For example, a gel, powder, a liquid, a granule, cream form, a paste form, solid etc. can be mentioned. Further, the type of the food and beverage composition of the present invention is not particularly limited, and examples thereof include confectionery (chewing gum, candy, gummi, tablet, chocolate, jelly, etc.), ice confectionery (ice candy, ice cream, sorbet, etc.), and frozen confectionery. (Jelly, pudding, water yokan, etc.), starch-based foods such as noodles, powdered foods and drinks, beverages (soups, coffee, teas, juices, carbonated beverages, cocoa, alcoholic beverages, jelly drinks, etc.), bakery foods (Cookies, biscuits, breads, pies, cakes, etc.), fats and oils (margarine, shortening, fat spreads, etc.), dairy products (milk, yogurt, whey drinks, lactic acid bacteria beverages, butter, cream, cheese, etc.) Can do.

Each of the food and beverage composition of the present invention can be produced by a conventional method, and if necessary, the following components are appropriately selected within a range not impairing the object of the present invention, and arginyl fructosyl glucose alone or arginyl It can be blended with a tyrosinase activity inhibitor, a melanin production inhibitor or a whitening agent containing a fructosylglucose-containing mixture as an active ingredient. For example, sugar sweeteners (monosaccharides such as fructose, glucose, tagatose and arabinose, oligosaccharides such as lactose, oligosaccharides, maltose and trehalose, powdered starch syrup, dextrin, sugar alcohol etc.), high sweetness sweeteners (sucralose, Acesulfame K, stevia, etc.), polysaccharides such as starch, fats and oils, dairy products, stabilizers, emulsifiers, fragrances (vanillin, linalool, natural fragrances, etc.), pigments, colorants, acidulants, flavor ingredients (eggs, coffee, Tea, cocoa, fruit pulp, yogurt, alcoholic beverages, etc.), flavoring (raspberry flavor, apple flavor, coffee flavor, etc.), anti-wetting agent, electrolyte, antioxidant, preservative, wetting agent, protein, amino acid, peptide , Dietary fiber, organic acids (citric acid, malic acid, fumaric acid, malonic acid, succinic acid, tartaric acid, lactic acid, etc.), vitamins (L-Asco Binic acid, dl-α-tocopherol, vitamin B1, vitamin B2, niacin, pantothenic acid, vitamin B6, vitamin B12, folic acid, biotin, inositol, etc., mineral (zinc, iron, calcium, magnesium, chromium, selenium, potassium, Sodium, etc.), glucosamine, yeast, eggshell membrane, lycopene, astaxanthin, other carotenoids, silk, chondroitin, ceramide, placenta extract, shark fin extract, deep-sea cocoon extract, squalene, γ-aminobutyric acid, casein decapeptide, raw chestnut skin extract , Chestnut leaf extract, chestnut potato extract, chestnut pulp extract, chestnut bark extract, cabbage ferment extract, rose petal extract, grape leaf extract, grape seed extract, apple polyphenol, chamomile extract, Lychee seed extract, Gotsukola extract Moon peach leaf extract, lotus germ extract, star fruit leaf extract, mulberry leaf extract, guava tea extract, red wine, green tea, black tea, oolong tea, coffee, cocoa, chocolate, black sesame, beans, soy milk, nuts, mushrooms, Green-yellow vegetables, egg-derived raw materials such as iodine eggs, catechins, other polyphenols, raspberry ketone, low molecular weight alginic acid, psyllium seed coat, ginkgo biloba extract, pine bark extract, nattokinase, plant sterol, diacylglycerol, chitosan, Examples include hyaluronic acid, methylsulfonylmethane, kojic acid, ellagic acid, arbutin, lucinol, magnolignan, magnesium phosphate L-ascorbate, CoQ10, and α-lipoic acid.

The dosage form of the pharmaceutical composition of the present invention is not particularly limited, and it may be an oral administration formulation or a parenteral administration formulation. Specifically, aerosols, liquids, extracts, elixirs, capsules (hard capsules, soft capsules, microcapsules), granules, pills, ophthalmic ointments, transdermal preparations, suspensions, emulsions, seats Preparation (vaginal preparation), powder, spirits, tablets (plain tablet, coated tablet, special tablet), syrup, soaking agent, decoction, injection (water-soluble injection, water-insoluble injection), patch, tincture Agents, eye drops, lozenges, ointments, poultices, fragrances, liniments, limonades, flow extracts, lotions and the like. These preparations can be produced by a conventional method in the pharmaceutical technical field, for example, by the method described in the Japanese Pharmacopoeia. These preparations can be safely administered to mammals including humans.

The pharmacologically acceptable carrier is not particularly limited, and various carrier substances known as pharmaceutical materials can be used. The carrier substance is not particularly limited, and examples of solid carriers include excipients, lubricants, binders, and disintegrants. In addition to the carrier substance, formulation additives such as preservatives, colorants, natural pigments, sweeteners and the like can be used as necessary. These substances include lactose, hydroxypropylmethylcellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, ethylcellulose, corn starch, crystalline cellulose, carmellose calcium, anhydrous silicic acid, synthetic aluminum silicate, magnesium stearate, talc, etc. Although it can illustrate concretely, it is not restricted to these.

The carrier substance in the liquid preparation is not particularly limited, and examples thereof include a solvent, a solubilizing agent, a suspending agent, a tonicity agent, a buffering agent, and the like. Furthermore, formulation additives such as preservatives, colorants, water-insoluble lake pigments, sweeteners and the like can be used as necessary. These substances include isotonic agents such as mannitol, sodium chloride, glucose, sorbitol, glycerol, xylitol, fructose, maltose, mannose, stabilizers such as sodium sulfite, preservatives such as benzyl alcohol and methyl parahydroxybenzoate. In addition to the above, a solubilizer, a soothing agent, a pH adjuster and the like can be specifically exemplified, but are not limited thereto.

Hereinafter, the present invention will be specifically described by illustrating examples and comparative examples. In addition, this invention is not limited at all by these Examples.

・ Sample preparation (production of arginyl fructosyl glucose)
A mixture of 2 g of arginine, 5 g of maltose and 50 ml of glacial acetic acid was heated and stirred at 80 ° C. for 30 minutes. The obtained solution was filtered, and the filtrate was concentrated and dried to obtain 4.7 g of a mixture. This is redissolved in 50 ml of water, applied to a column filled with a cation exchange resin, and eluted with 1% aqueous ammonia. The eluate was concentrated and freeze-dried to obtain 2.4 g of arginyl fructosyl glucose fraction. The obtained arginyl fructosyl glucose fraction (2.4 g) was purified with a silica gel column and Biogel P-2 to obtain 0.26 g of arginyl fructosyl glucose.

-Measurement of tyrosinase activity inhibitory activity The arginyl fructosyl glucose obtained in the above production was measured for its tyrosinase activity inhibitory activity using L-tyrosine as a substrate. As an experimental operation method, 0.2 ml of arginyl fructosyl glucose prepared to have an addition concentration shown in Table 1 in 0.2 ml of 2 mM L-tyrosine solution, 0.02 ml of tyrosinase solution (200 μg / ml), and 0. 0.2 ml of 1M phosphate buffer (pH 7.0) was added, mixed well, reacted at 37 ° C. for 15 minutes, and the absorbance at 475 nm was measured. The same procedure was applied to the case of no addition of arginyl fructosyl glucose, the absorbance at 475 nm was measured, and the tyrosinase inhibition rate of arginyl fructosyl glucose was calculated. Table 1 shows the measurement results of the tyrosinase activity inhibitory action of arginyl fructosyl glucose.

As is clear from the results shown in Table 1, arginyl fructosyl glucose exhibited a tyrosinase activity inhibitory effect in a concentration-dependent manner.

Below, the Example of the cosmetics and pharmaceutical composition of this invention is shown. The composition is expressed in wt%.

(Example 4) Toner lotion wt%
Arginyl fructosyl glucose 0.1
N-acetylglucosamine 0.05
Ethanol 7.5
Placenta extract 0.05
D-pantothenyl alcohol 0.1
Dipotassium glycyrrhizinate 0.1
Phenoxyethanol 0.3
Polyoxyethylene sorbitan monolaurate (20E.O.) 0.3
Polyoxyethylene hydrogenated castor oil 0.05
Edetate disodium 0.05
Concentrated glycerin 3.5
1,3-butylene glycol 2.5
Polyglycerin 0.5
Xanthan gum 0.5
Sorbit liquid 5.0
Carboxyvinyl polymer 0.1
Purified water to100

(Example 5) Latex wt%
Arginyl fructosyl glucose 0.1
D-pantothenyl alcohol 0.1
Dipotassium glycyrrhizinate 0.1
Liquid paraffin 10.0
Concentrated glycerin 5.0
Dipropylene glycol 10.0
Sorbit liquid 5.0
White beeswax 0.5
Liquid paraffin 1.5
Lipophilic glyceryl monostearate 0.1
Stearic acid 0.3
Methyl polysiloxane 1.0
Vaseline 1.0
Cholesterol 0.02
Bentonite 0.1
N-stearoyl-L-glutamate sodium 0.3
Xanthan gum 0.2
Behenyl alcohol 0.3
Phenoxyethanol 0.2
Sodium hyaluronate (2) 0.05
Water-soluble collagen (F) 0.1
Vaginal ovary extract 0.1
Paraoxybenzoic acid ester 0.1
N-acetylglucosamine 0.05
Purified water to100

(Example 6) Cream wt%
Arginyl fructosyl glucose 0.1
D-pantothenyl alcohol 1.0
Dipotassium glycyrrhizinate 0.5
Liquid paraffin 4.0
White beeswax 0.5
Cholesterol 1.0
Methylcyclopolysiloxane 2.0
Dipropylene glycol 7.0
Lipophilic glyceryl monostearate 0.3
Sodium cetyl sulfate 1.0
Polyethylene glycol monostearate 1.0
Sodium hyaluronate (2) 0.5
Water-soluble collagen (F) 0.1
Phenoxyethanol 0.5
Edetate disodium 0.05
N-acetylglucosamine 0.05
Purified water to100

(Example 7) Pack wt%
Arginyl fructosyl glucose 0.5
Talc 25.0
Propylene glycol 6.0
KCl 0.1
Perfume proper amount kaolin to100

(Example 8) Latex wt%
Arginyl fructosyl glucose 0.2
Stearic acid 2.0
Cetanol 2.0
Vaseline 2.0
Lanolin alcohol 1.5
Liquid paraffin 9.0
Squalane 3.5
Sorbitol 10.0
Triethanolamine 1.0
Propylene glycol 5.0
Preservative appropriate amount perfume appropriate amount purified water to100

(Example 9) Nutritional cream wt%
Arginyl fructosyl glucose 1.0
Stearic acid 2.0
Stearyl alcohol 8.0
Reduced lanolin 2.0
Squalane 8.0
Octyldodecanol 6.0
Preservative Appropriate amount Fragrance Appropriate amount Propylene glycol 5.0
Glycerin 3.0
Lactic acid 0.3
Sodium citrate 0.5
Purified water to100

(Example 10) Slimming Massage Gel wt%
Arginyl fructosyl glucose 2.0
Glycerin 60.0
PEG200 14.0
Polyvinyl alcohol 0.2
Purified water to100

(Example 11) Slimming massage soap wt%
Arginyl fructosyl glucose 5.0
Lauric acid 10.0
Potassium hydroxide 2.8
Coconut oil fatty acid potassium 30.0
Edetate disodium 0.15
Methylcellulose 0.5
Aminopropyl betaine laurate solution 2.0
Glycerin 8.0
Perfume proper amount purified water to100

(Example 12) Massage gel wt%
Arginyl fructosyl glucose 0.5
Caffeine 0.1
Carboxyvinyl polymer 0.5
Polyvinyl alcohol 3.0
Glycerin 35.0
Polyethylene glycol 400 45.0
Ethanol appropriate amount Preservative appropriate amount purified water to100

Each cosmetic of Examples 4 to 12 was in accordance with a normal cosmetic production method. Arginyl fructosyl glucose used was a purified sample produced by the same production method as that used in Examples 1-3. All cosmetics improved stains, freckles, and pigmentation after sunburn by continuous use.

(Example 13) Granules wt%
Arginyl fructosyl glucose 10.0
Starch 30.0
Lactose 49.0
Crystalline cellulose to100
The above-mentioned respective parts by weight were uniformly mixed and prepared by a conventional method to prepare granules.

(Example 14) Tablet wt%
Arginyl fructosyl glucose 1.0
Crystalline cellulose 1.5
Vitamin C 20.0
Fragrance 1.0
Guam gum 0.1
DK ESTER 1.5
Powdered sugar to100

(Example 15) Soft capsule wt%
Arginyl fructosyl glucose 3.0
Vitamin E 20.0
Wheat germ oil 15.0
Glycerin fatty acid ester 5.0
Beeswax 2.0
Perilla oil to100
The above components were mixed and filled in a ceratin film made of gelatin and glycerin to obtain a soft capsule according to a conventional method.

(Example 16) Hard capsule wt%
Arginyl fructosyl glucose 15.0
Sodium ascorbate 18.0
Dextrin 24.0
Glycerin fatty acid 0.5
Powdered sugar to100
The above components were mixed and filled into a capsule container made of gelatin to obtain a hard capsule according to a conventional method.

All pharmaceutical compositions improved stains, freckles, and pigmentation after sunburn.

Claims (3)

A tyrosinase activity inhibitor characterized by containing arginyl fructosyl glucose as an active ingredient (excluding those used as a form of a food or beverage composition). A melanin production inhibitor characterized by containing arginyl fructosyl glucose as an active ingredient (except for those used as a form of a food or beverage composition). A whitening agent for preventing or treating pigmentation characterized by containing arginyl fructosyl glucose as an active ingredient (except for those used as a form of a food or beverage composition) .