JP2009196895A - Tyrosinase inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new tyrosinase inhibition activator, and to provide a skin-lightening composition containing the inhibitor. <P>SOLUTION: Provided are the tyrosinase inhibitor containing echinacoside represented by chemical formula (1) (wherein, R<SB>1</SB>is H; R<SB>2</SB>is α-L-rhamnopyranose; R<SB>3</SB>is trans-caffeoyl; R<SB>4</SB>is β-D-glucopyranose; R<SB>5</SB>is OH) as an active ingredient, and the bleaching composition containing the inhibitor. The echinacoside can be obtained by extracting a Cistanche family plant. The skin-lightening composition can widely be used as a medicine, an external preparation for skin, a food, a drink, or a feed for mammals. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a tyrosinase inhibitor using a novel component, and a whitening composition using the same. The present invention is widely used for medicines for mammals including humans, external preparations for skin, foods and the like.

  Conventionally, it has been known that fresh stalks of herbs belonging to the family Cistanche are effective in treating infertility, impotence, constipation, and the like (see Patent Document 1). In addition, preparations obtained from fresh perennial herb stems provide blood and kidney nutrition. These parasites and perennial herbs are widely cultivated in the northwestern region of China and are known in some regions as “desert ginseng”. The most cultivated species of Cistanche are all parasitic plants [Cistanche tubulosa].

  Japanese scientists have systematically studied the chemical composition and pharmacological activity of Cistanche, and found that phenylethanoid glycosides are the main active ingredients of these perennial herbs (eg Non-patent documents 1 to 3). Such active ingredients are effective antioxidants, metabolism promoters, memory promoters, libido promoters and the like. The medical properties of various phenylethanoid glycoside compounds have been studied by many researchers.

  On the other hand, factors such as slimming, skin beautification, and whitening are known in beauty, and pigmentation after inflammation such as spots, freckles, darkness, senile plaques, wounds and burns is regarded as a cosmetic problem. There is a growing awareness of whitening, especially among women. In the pigmentation, stimuli such as ultraviolet rays and inflammation activate melanoma cells in the dermal tissue, and tyrosinase, an enzyme contained in melanoma cells, oxidizes and polymerizes tyrosine, a biological component, to produce melanin, a dark brown pigment. The mechanism to do this has been clarified. Therefore, beauty foods and drinks and cosmetics containing various animal and plant extracts have been proposed for the purpose of obtaining a whitening effect by inhibiting the activity of tyrosinase.

JP 2004-250449 A Sato T., et al. Yakugaku Zasshi, 1985, 105 (12): 1131 Jimenez C., et al. Nat Prod Rep, 1994, 11 (6): 591 Cometa F., et al. Fitoterapia, 1993, 64 (3): 195

  Under such a background, the present inventors have found that echinacoside, which is one of the main components contained in the plant of the genus Oleaceae, has tyrosinase inhibitory activity, and completed the present invention. That is, an object of the present invention is to provide a novel tyrosinase inhibitor and a whitening composition containing them.

In order to solve the above problems, the present invention has the following characteristics.
1. A tyrosinase inhibitor comprising echinacoside as an active ingredient.
2. The echinacoside is extracted from a plant of the genus Oleaceae. A tyrosinase inhibitor according to claim 1.

3. Above 1. Or 2. A whitening composition comprising the tyrosinase inhibitor described in 1.
4). 3. above. A pharmaceutical product for mammals including humans, comprising as an active ingredient the composition for whitening described in 1.
5. 3. above. An external skin preparation for mammals including humans, comprising the whitening composition described in 1 above as an active ingredient.
6). 3. above. Food / beverage products which use the whitening composition as described in 1 for an active ingredient.
7). 3. above. A mammal animal feed comprising the whitening composition as described in 1 above as an active ingredient.

Hereinafter, the present invention will be described in detail.
The present invention is a tyrosinase inhibitor characterized by containing echinacoside.

Here, the “echinacoside” is one type of phenylethanoid glycoside, and the “phenylethanoid glycoside” refers to a compound represented by the following chemical formula (1).
Here, Echinacoside is
R ₁ = H
R ₂ = α-L-Rhamnopyranose
R ₃ = trans-Caffeoyl
R ₄ = β-D-Glucopyranose
R ₅ = OH
Refers to the ingredients.

The method for obtaining echinacoside is not particularly limited, and it may be obtained by synthesis or may be obtained by extraction from a plant.
Moreover, when extracting from a plant, the plant used as a raw material is not specifically limited, For example, the ground medicine which is a crude drug, the rhododendron plant chorogi, the pepper family pepper genus, the olive fruit, the herbaceous plant herbaceous plant etc. are mentioned. These may be used alone or in combination of two or more. Of these, it is most preferable to use plants of the family Amaranthaceae. This is because it has a higher concentration of echinacoside and thus has higher tyrosinase inhibitory activity.
Here, the plant of the Amaranthaceae used as a raw material is not specifically limited, For example, all parasitic plants [Cistanche tubulosa: kankanikusuyo], hononiku (Cistanche salsa: nikujuyou), nanbangicellu (Aeginetia indica), oyster (Boschniakia rossica) However, it is not limited to these. These may be used alone or in combination of two or more. Of these, the whole parasitic plant [Cistanche tubulosa: kankanikujuyou] is particularly preferable.

  Here, the part of the plant of the Amaranthaceae extracted is not particularly limited, and may be any of leaves, roots, stems and the like as long as a desired effect is obtained. Preferably, it is extracted from the stems of the genus Oleaceae, in particular fresh stems.

  The method for obtaining echinacoside from the starting plant of the genus Oleaceae is not particularly limited, and examples thereof include solvent extraction and supercritical extraction.

Moreover, when extracting by a solvent extraction method, the solvent to be used is not specifically limited, However, It is preferable to use a polar solvent. Moreover, although the said polar solvent is not specifically limited, For example, water, methanol, ethanol, isopropanol, acetone, 1, 3- butylene glycol, ethylene glycol, propylene glycol, glycerol, acetic acid, ethyl acetate, ether etc. are mentioned. These may be used alone or in combination of two or more.
This is because it is possible to easily obtain an extract containing echinacoside, which is preferably subjected to further treatments such as dilution, concentration, drying and purification.
Examples of the purification method include activated carbon treatment, resin adsorption treatment, ion exchange resin, liquid-liquid countercurrent distribution, and the like.

One embodiment of a specific method for producing the extract is described in detail below. In addition, the manufacturing method of an extract is not limited to the following.
The manufacturing method of the said extract consists of two steps, extraction and refinement | purification. In the first stage, the stems of the genus Oleaceae (for example, the whole parasitic plant [Cistanche tubulosa]), more preferably the fresh stems of the plant, are cut into flakes, or fine particles or powder Grind into a shape. Next, the flakes, fine particles or powder thus obtained are immersed in a solvent such as water, a lower aliphatic alcohol such as ethanol or methanol, or a mixture thereof. At this time, the extraction is performed at room temperature. Next, the mixed solution is filtered, and the filtrate is concentrated under reduced pressure or in vacuo to obtain an extract. Next, as a second step, the extract is heated in water and then transferred to an adsorption column packed with macroporous adsorption resin to purify the extract. At this time, the column is eluted using water, methanol, ethanol, a mixed solution of water and methanol, or a mixed solution of water and ethanol as an elution solvent. The elution may be carried out by using an elution solvent as described above in a solution having a constant concentration or by adding a concentration gradient to the solution. The eluate is collected and concentrated, and then dried by a known drying method. When the eluate has dried, the extract is obtained. The extract thus obtained contains echinacoside.
A high concentration of echinacoside can be obtained by concentrating and purifying the extract as necessary.
As this echinacoside, a commercially available product can be used. For example, a product manufactured by Kyohada Industrial Co., Ltd. can be used.

  The tyrosinase inhibitor of the present invention may contain other phenylethanoid glycosides in addition to echinacoside. The phenylethanoid glycoside included at this time is not particularly limited, and examples thereof include acteoside, 2'-acetylacetoside; campneoside I; campneoside II; Cistantubuloside A, B1, B2, C1, C2; crenatoside; decaffeoylacteoside; isoacteoside; rhodioloside; syringalide A; 3'-α-L-rhamnopyranoside, tubuloside and the like can be mentioned. In this case, the above components may be included alone or in the form of a mixture of two or more.

  The tyrosinase inhibitor of this invention can be used as a raw material of various food-drinks. Examples of food and drink include edible oil (salad oil), confectionery (gum, candy, caramel, chocolate, cookie, snack, jelly, gummy, tablet confection etc.), noodles (soba, udon, ramen etc.), dairy products ( Milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated drinks, sports drinks, etc.) and health foods (tablets , Capsules, etc.) and nutritional supplements (nutrient drinks, etc.). The cosmetic composition of the present invention may be appropriately blended with these foods and drinks.

These foods and drinks can be blended with various ingredients depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid. Acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, Food materials such as carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances and preservatives can be used. In addition, this tyrosinase inhibitor with health maintenance functions includes other antioxidants and health food ingredients such as antioxidants, reduced ascorbic acid (vitamin C), vitamin E, and reduced glutatin. , Tocotrienol, vitamin A derivative, lycopene, β-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sezamin, lignans, catechin, isoflavone, chalcone, tannins, flavonoids , Coumarin, isocoumarins, blueberry extract, arbutin, tannin, anthocyanin, apple polyphenol, grape seed extract, ellagic acid, kojic acid, surge extract health food material, V. (vitamin) A, V.B1, V.B2 , V.B6, V.B12, VC, VD, VE, VP, choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharide, dietary fiber, squalene, soy lecithin, taurine, donariella, protein, octacosanol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, zinc, chromium, selenium , Potassium, heme iron, oyster meat extract, chitosan, chitin oligosaccharide, collagen, chondroitin, turmeric, licorice, kokushi, keihi, hawthorn, ginger, ganoderma, swordfish extract, suppon, licorice, kukoshi, keihi, hawthorn, ginger, Ganoderma, plantain, chamomile, chamomile, dandelion, hibiscus, honey, boren, royal jelly, lime, lavender, rosehip, rosemary, sage, bifidobacteria, faecalis, lacris, wheat germ oil, sesame oil Perilla oil, soybean oil, medium chain fatty acid, agaricus, ginkgo biloba extract, turmeric, chondroitin, brown rice germ extract, litchi, onion, DHA, EPA, DPA, green tea, cordyceps, garlic, bee, papaya, puer, propolis, Meguri Tree, Yabushake, Royal Jelly, Saw Palmetto, Hyaluronic Acid, Collagen, Gabba, Harp Seal Oil, Shark Cartilage, Glucosamine, Lecithin, Phosphatidylserine, Seven Carrots, Mulberry Leaf, Soybean Extract, Echinacea, Ezoukogi, Barley Extract , Olive leaf, olive fruit, Gymnema, Banaba, Salacia, Garcinia, Chitosan, St. John's wort, jujube, carrot, passion flower, broccoli, placenta, pearl barley, grape seeds, peanut seed coat, bilberry, black cohosh, Maria Thistle, laurel, sage, rosemary, black vinegar, bitter gourd, maca, safflower, flax, oolong tea, flower spine, caffeine, capsaicin, xylooligosaccharide, glucosamine, buckwheat, citrus, dietary fiber, protein, prunes, spirulina, Barley young leaves, nucleic acids, yeast, shiitake mushrooms, plum meat, amino acids, deep sea potato extract, noni, oyster meat, suppon, champignon, plantain, acerola, pineapple, banana, peach, apricot, melon, strawberry, raspberry, orange, fucoidan, Meshimakobu, Cranberry, Chondroitin Sulfate, Zinc, Iron, Ceramide, Silk Peptide, Glycine, Niacin, Chest Tree, Ceramide, L-Cysteine, L-Carnitine, Red Wine Leaf, Millet, Horsetail, Biotin, Centella Asiatica, Hascup, Pycnogeno , Buffalo, rhubarb, clove, rosemary, catechin, puer, citric acid, brewer's yeast, merirot, black zinger, ginger, gadget, nattokinase, benichouji, tocotrienol, lactoferrin, cinnamon, persimmon buckwheat, cocoa, yuzu seed extract, Perilla seed extract, lychee seed extract, evening primrose extract, black rice extract, α-lipoic acid, gabba, fresh coffee bean extract, burdock extract, kiwi seed extract, Unshu mandarin orange extract, red ginger extract, astaxanthin) .

  As a specific production method, the tyrosinase inhibitor of the present invention is spray-dried or freeze-dried together with powdered dextrin in the case of an extract, and this is easily converted into a powder, granule, tablet or solution. Food) and the like. If necessary, it can also be mixed with a binder such as gum arabic to form a powder or granules, and added to a solid food. In the case of an extract, it can also be added to a beverage as it is or after being dispersed and dissolved in water, ethanol, glycerin or a mixture thereof.

  The tyrosinase inhibitor of the present invention may be used as a raw material for drugs (including drugs and quasi drugs). It can be produced by appropriately blending the tyrosinase inhibitor of the present invention with a raw material for a pharmaceutical preparation. In addition, the said chemical | medical agent may be used for a human and may be used for mammals other than a human. Examples of the pharmaceutical raw material that can be blended in the tyrosinase inhibitor of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cocoa butter, hydrogenated vegetable oil, kaolin, talc, etc. ), Binder (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrant (sodium alginate, agar, sodium bicarbonate) , Calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose, gum arabic powder, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cocoa butter, hydrogenated oil, etc.), absorption enhancers (quaternary) Ammonium base, sodium lauryl sulfate Etc.), adsorbents (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, and the like) and the like.

  The administration method of the tyrosinase inhibitor according to the present invention can be generally administered orally in the form of tablets, pills, soft / hard capsules, fine granules, powders, granules and the like. The water-soluble preparation can be administered orally as a liquid. Furthermore, parenteral administration may be used. When administered as a parenteral agent, the tyrosinase inhibitor of the present invention is dispersed in a suitable solubilizing agent such as ethanol or water, and then in a dosage form such as a poultice, lotion, ointment, tincture or cream. Can be applied. In addition, the water-soluble preparation of the present tyrosinase inhibitor can be used as it is or in the form of a poultice, lotion, ointment, tincture, cream, etc. with a dispersant, suspension, stabilizer, etc. added. Can be applied.

  The dose may vary depending on the administration method, medical condition, age of the patient, etc., but for adults, it can be generally administered in an amount of about 5 to 200 mg as an active ingredient per day and usually about 0.5 to 100 mg for children.

The compounding ratio when using the tyrosinase inhibitor of the present invention as a drug can be appropriately changed depending on the dosage form, but is usually about 0.01 to 10 wt% when administered orally or by mucosal absorption, In the case of parenteral administration, it should be about 0.01 to 20 wt%. In addition, since the dose varies depending on various conditions, a dose smaller than the above dose may be sufficient, or it may be necessary to administer beyond the range. In addition to the tyrosinase inhibitor, the pharmaceutical composition may include other known compounds that are commonly used in the pharmaceutical field, and compounds that are necessary for molding into a form suitable for oral administration. Examples of such compounds include lactose, starch, hydroxypropyl cellulose, kaolin, talc, calcium carbonate and the like.

Further, the tyrosinase inhibitor of the present invention can be contained in mammalian animal feed. The animal feed can be contained in the same manner as the food and drink. The animal feed is not particularly limited. For example, it is used for domestic animals such as cattle and pigs, companion animals such as dogs, cats and hamsters (animals kept as pets). can do.
For example, flour, meat, etc. can be used as companion animal feed. At this time, examples of the flour include wheat flour, rice flour, rye flour, corn flour, millet flour, bubble flour, corn flour, and soybean flour, and these flours may be used in combination of two or more. By using flour, nutrients such as carbohydrates can be supplied to companion animals. Among the above flours, it is most preferable to use flour, and as flour, strong flour, medium flour, thin flour can be used alone or in combination, and even when such flour and other flour are used in combination Good. Furthermore, in order to adjust the elasticity of the animal feed after the heat treatment, wheat flour, wheat gluten, soybean protein and the like may be combined. In addition, the network structure derived from gluten contained in wheat flour can constitute a puffed tissue structure when heat-treated, which contributes to improving the texture.

  The meat used in the present invention is not particularly limited, and chicken, pork, beef, mutton, goat meat, salmon meat, turkey meat, horse meat, etc. can be used, but chicken is preferably used in terms of flavor. The The above meat is obtained by slaughtering and demolishing livestock in the usual way. In addition, since the deterioration of the quality of a product with intermediate moisture or low moisture is mainly caused by fat oxidation, the meat to be used is preferably red meat from which the fat content is low or fat is removed. In addition, the coexistence of meat can improve the palatability of companion animals as well as strengthening high-quality animal proteins.

Even when the tyrosinase inhibitor of the present invention is used as an external preparation for skin (including cosmetics, pharmaceuticals and quasi drugs), a tyrosinase inhibitory action can be expected. In addition, the said skin external preparation may be used for a human and may be used for mammals other than a human.
Examples of the external preparation for skin to which the tyrosinase inhibitor of the present invention can be formulated include, for example, emulsion, soap, face wash, bath preparation, cream, emulsion, lotion, eau de cologne, shave cream, shave lotion, makeup Oil, sunscreen / sunscreen lotion, funny powder, foundation, perfume, pack, nail cream, enamel, enamel remover, eyebrow, blusher, eye cream, eye shadow, mascara, eyeliner, lipstick, lip balm, shampoo, rinse, Examples include hair dyes, dispersions, and cleaning materials.
Examples of the form of a pharmaceutical or quasi-drug that can contain the tyrosinase inhibitor of the present invention include ointments, creams, and liquids for external use.

In addition to the tyrosinase inhibitor according to the present invention, the external preparation for skin of the above-described form includes ingredients, oils, higher alcohols, and the like, which are blended in external preparations for skin such as cosmetics and quasi-drugs, as long as the tyrosinase inhibitory action is not impaired Fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyhydric alcohols / sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, preservatives, and the like can be blended.
Examples are listed below, but the present invention is not limited to these examples.

(1) Examples of oil components Ester-based oil phase components: glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearic acid Isocetyl, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine Diisopropyl acid, isoaralkyl neopentanoate, glyceryl tri (capryl / caprate), trimethylolpropane tri-2-ethylhexanoate, trimethylol triisostearate Propane, pentaerythritol tetra-2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isolaurate Stearyl, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl linoleate, octyldodecyl isoleate, isopropyl isostearate Cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethyleneglycol dioctanoate , Ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di (capryl / capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, triisopalmitine Glyceryl acid, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyl decyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleic acid Ester, polyglycerol isostearate, dipropyl carbonate, charcoal Dialkyl (C12-18), triisocetyl citrate, triisoaralkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyl decyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, Trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, olein Cholesteryl acid, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, 12-stearoyl hydroxystearate Cetyl, 12-stearoyl-hydroxystearic acid stearyl 12-stearoyl-hydroxystearic acid isostearate, and the like.
Hydrocarbon oil phase components: squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum and the like.
Animal and vegetable oils and their hydrogenated oils, and naturally occurring waxes: beef tallow, hydrogenated beef tallow, lard, hydrogenated tallow, horse oil, hydrogenated horse oil, mink oil, orange luffy oil, fish oil, hydrogenated fish oil, egg yolk oil and other animal oils and Its hardened oil, avocado oil, almond oil, olive oil, cacao butter, kiwi seed oil, apricot oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil , Perilla oil, tea seed oil, camellia oil, corn oil, rapeseed oil, hydrogenated rapeseed oil, palm kernel oil, hydrogenated palm kernel oil, palm oil, hydrogenated palm oil, peanut oil, hydrogenated peanut oil, castor oil, hydrogenated castor oil , Vegetable oils such as sunflower oil, grape seed oil, jojoba oil, hardened jojoba oil, macadamia nut oil, medhome oil, cottonseed oil, hardened cottonseed oil, coconut oil, hardened coconut oil and its hardened , Beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax and montan wax.
Silicone oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethyl Siloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic Examples include silicone, trimethylsiloxysilicic acid, and silicone RTV rubber.
Fluorine oil phase components: perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl / polyoxyalkylene co-modified organopolysiloxane, and the like.

(2) Examples of higher alcohols Lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, octyldodecanol and the like can be mentioned.

(3) Examples of fatty acids Caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid , Erucic acid, 2-ethylhexanoic acid and the like.

(4) Examples of UV absorbers Paraaminobenzoic acid, amyl paraaminobenzoate, ethyldihydroxypropyl paraaminobenzoate, glyceryl paraaminobenzoate, ethyl paraaminobenzoate, octyl paraaminobenzoate, octyldimethyl paraaminobenzoate, ethylene glycol salicylate, salicylic acid Octyl, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl paramethoxycinnamate, 2-ethylhexyl paramethoxycinnamate, mono-2-diparamethoxycinnamate Glyceryl ethylhexanoate, isopropyl paramethoxycinnamate, diethanolamine salt of paramethoxyhydrocinnamic acid, diisopropyl diisopropylcinnamic acid Stealth mixture, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, Butylmethoxydibenzoylmethane, 2,4,6-trianilino-p- (carbo-2-ethylhexyl-1-oxy) -1,3,5-triazine, 2- (2-hydroxy-5-methylphenyl) benzotriazole , Methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3, 3-diphenyl acrylate, phenylbenzimidazole sulfate, 3- (4-methylbenzylidene) can Examples include full, isopropyldibenzoylmethane, 4- (3,4-dimethoxyphenylmethylene) -2, 5-dioxo-1-imidazolidinepropionate 2-ethylhexyl, and the like, polymer derivatives, silane derivatives, and the like.

(5) Examples of powders and pigments Red 104, Red 201, Yellow 4, Blue 1, Black 401 and other dyes, Yellow 4 AL lake, Yellow 203 BA lake and other lake dyes, nylon powder , Silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polyethylene powder, yellow iron oxide, red iron oxide, black Colored pigments such as iron oxide, chromium oxide, carbon black, ultramarine and bitumen, white pigments such as zinc oxide, titanium oxide and cerium oxide, extender pigments such as talc, mica, sericite, kaolin and barium sulfate plate, titanium mica Pearl pigments such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, metal salts such as magnesium silicate, Inorganic powders such as Rica and alumina, metal soaps such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, zinc undecylenate, bentonite, smectite, boron nitride, etc. It is done. There are no particular restrictions on the shape of these powders (spherical, rod-like, needle-like, plate-like, irregular shape, flake-like, spindle-like, etc.) and particle diameter. These powders are conventionally known surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine treatment, The surface treatment may or may not be performed in advance by polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment or the like.

(6) Examples of surfactants Anionic surfactants: fatty acid soap, α-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate , Alkylamide sulfate, alkyl phosphate, POE alkyl phosphate, alkylamide phosphate, alkyloylalkyl taurine salt, N-acyl amino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, alkyl sulfoacetic acid Sodium, acylated hydrolyzed collagen peptide salt, perfluoroalkyl phosphate, etc. are mentioned.
Cationic surfactant: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride , Behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide, lanolin derivative quaternary ammonium salts, and the like.
Amphoteric surfactants: carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amidoamine type and the like.
Nonionic surfactant: Propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbit fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE cured castor Oil, POE castor oil, POE / POP copolymer, POE / POP alkyl ether, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, and the like.
Natural surfactant: lecithin, saponin, sugar surfactant and the like.

(7) Examples of polyhydric alcohols and sugars Ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1, 3 -Butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan and the like. These chemically modified compounds can also be used.

(8) Examples of polymers Acrylic ester / methacrylic acid ester copolymer (plus size, manufactured by Kyoyo Chemical), vinyl acetate / crotonic acid copolymer (resin 28-1310, manufactured by NSC), vinyl acetate / croton Acid / vinyl neodecanate copolymer (28-2930, manufactured by NSC), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP), T-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (rubymer) , BASF), vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer (Rubicol VAP, BASF), vinyl acetate / crotonic acid copolymer (Rubiset CA, BASF), vinyl acetate / croton Acid / vinyl pyrrolidone copolymer (Rubiset CAP, manufactured by BASF), vinyl pyrrolidone / acrylate copolymer (Rubiflex, BA SF), acrylate / acrylamide copolymer (Ultrahold, BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer (Advantage, ISP), carboxy vinyl polymer (Carbopol, BF Goodrich), anionic polymer compounds such as acrylic acid / alkyl methacrylate copolymers (Pemulene, BF Goodrich) and acetic acid amphoteric compounds of dialkylaminoethyl methacrylate polymers (Yukaformer, Mitsubishi Chemical) Amphoteric polymer compounds such as octyl acrylate acrylate / hydroxypropyl acrylate / butyl aminoethyl methacrylate copolymer (AMPHOMER, NSC), quaternized vinylpyrrolidone / dimethylaminoethyl methacrylate (GAFQUAT, ISP) , Methyl vinyl imidazolium chloride Cationic polymer compounds such as vinyl / vinylpyrrolidone copolymer (rubicoat, manufactured by BASF), polyvinylpyrrolidone (rubiscol K, manufactured by BASF), vinylpyrrolidone / vinyl acetate copolymer (rubiscol VA, manufactured by BASF) ), Nonionic polymer compounds such as vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer 937, manufactured by ISP), vinylcaprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer VC713, manufactured by ISP), etc. There is. Cellulose or derivatives thereof, keratin and collagen or derivatives thereof, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabino Naturally derived polymer compounds such as galactan, gum karaya, gum tragacanth, alginic acid, albumin, casein, curdlan, gellan gum and dextran can also be suitably used.

(9) Examples of physiologically active ingredients Examples of physiologically active ingredients include substances that impart some physiological activity to the skin when applied to the skin. For example, whitening ingredients, immunostimulants, anti-aging agents, UV protection agents, slimming agents, tanning agents, antioxidants, hair growth agents, hair restorers, moisturizers, blood circulation promoters, antibacterial agents, bactericides, desiccants, A cooling sensation agent, a warming sensation agent, vitamins, an amino acid, a wound healing promoter, an irritation relaxation agent, an analgesic agent, a cell activator, an enzyme component, etc. are mentioned. Examples of these suitable ingredients include, for example, ashitaba extract, avocado extract, amateur extract, altea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract, ages Extract, Echinacea leaf extract, Ogon extract, Oat extract, Oen extract, Barley extract, Hypericum extract, Oyster extract, Dutch mustard extract, Orange extract, Seawater dried product, Seaweed extract, Hydrolyzed elastin, Hydrolyzed wheat powder, Hydrolyzed silk , Chamomile extract, Carrot extract, Kawara mugwort extract, Licorice extract, Calcade extract, Oyster extract, Kina extract, Cucumber extract, Guanosine, Gardenia extract, Kumazasa extract, Clarae Kiss, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentian extract, tea extract, yeast extract, burdock extract, fermented rice bran extract, rice germ oil, comfrey extract, collagen, bilberry extract, saicin extract, psycho extract Extract Kizuta extract, hawthorn extract, elderberry extract, yarrow extract, mint extract, sage extract, mallow extract, senki Sue extract, assembly extract, soybean extract, tiso extract, thyme extract, tea extract, clove extract, chigaya extract, chimpi extract, touki extract, toshinsen extract, tonin extract, spruce extract, dokudami extract, tomato extract, natto extract, carrot extract, garlic extract, Novara extract, hibiscus extract, bacmond extract, parsley extract, honey, hamamelis extract, parietalia extract, toad extract, bisabolol, loquat extract, dandelion extract, burdock extract, bukuro extract, butcher bloom extract, grape extract, propolis, loofah extract, Safflower extract, peppermint extract, bodaige extract, button extract, hop extract, pine extract, marronnier extract, mizubasho Kiss, Mukuroji extract, Melissa extract, Peach extract, Cornflower extract, Eucalyptus extract, Yukinoshita extract, Yokuinin extract, Artemisia extract, Lavender extract, Apple extract, Lettuce extract, Lemon extract, Lotus root extract, Rose extract, Rosemary extract, Roman chamomile extract And royal jelly extract.
Biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membranes, amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidonecarboxylate , Moisturizing ingredients such as betaine, whey, trimethylglycine, oily ingredients such as sphingolipid, ceramide, phytosphingosine, cholesterol, cholesterol derivatives, phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, Immunostimulants such as hydrocortisone, vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester Vitamins, active ingredients such as allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, antioxidants such as tocopherol, carotenoid, flavonoid, tannin, lignan, saponin, α-hydroxy acid, β-hydroxy acid, etc. Cell activators, blood circulation promoters such as γ-oryzanol and vitamin E derivatives, wound healing agents such as retinol and retinol derivatives, arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione, etc. Whitening agent, cephalanthin, licorice extract, red pepper tincture, hinokitiol, garlic iodide extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivative, calcium pantothenate, D-pan Tothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethinyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonyl acid vanillylamide, nonanoic acid vanillylamide, pyroctone Olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcin, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormone, cantalis tincture, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, monostearic acid Examples include hair growth agents such as polyoxyethylene sorbitan, mint oil, and Sasanishiki extract.

(10) Examples of antioxidants Sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolyl biguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxy Examples include plant extracts having an antioxidant effect such as toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoid, flavonoid, tannin, lignan, saponin, apple extract and clove extract.

(11) Examples of solvents Purified water, ethanol, lower alcohol, ethers, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile linear silicone, next-generation chlorofluorocarbon and the like.

Examples of the present invention will be described, but the present invention is not limited to these examples.
As an example sample, pure echinacoside (manufactured by Kyokusei Kogyo Kogyo Co., Ltd.) was used.
50 μL of a sample solution prepared in 10% DMSO and 45 μL of 0.1 M phosphate buffer (pH 7.0) were mixed so that the samples had final reaction concentrations of 30, 100, 300, and 1000 μg / mL, respectively. Thereafter, 5 μL of 1100 U / mL tyrosinase (derived from mushrooms, Sigma) was added, and preincubation was performed at 37 ° C. for 10 minutes. 0.15% here
After adding L-DOPA (50 μL), the mixture was further incubated at 37 ° C. for 5 minutes, and the absorbance at 490 nm was measured with a microplate reader. In addition, in order to investigate the influence of the sample, a test was performed blind (Blank) in which only the solvent was added instead of 0.15% L-DOPA, and a control (Control) in which only the solvent of the sample was added instead of the sample solution. The same operation was performed. The absorbance difference of the echinacoside-added sample with respect to the absorbance difference in the case of the sample not added with echinacoside of this example (control) was defined as the tyrosinase activity rate. The result is shown in FIG.
According to FIG. 1, echinacoside (1000 μg / mL) showed a significant tyrosinase inhibitory action, so that echinacoside has a whitening function, so that echinacoside can be used as a whitening composition.

  Examples of blending the tyrosinase inhibitor of the present invention are given below, but the following blending examples do not limit the present invention.

Formulation Example 1: Chewing gum
53.0wt% sugar
Gum base 20.0
Glucose 10.0
Minamata 16.0
Fragrance 0.5
Tyrosinase inhibitor 0.5
100.0wt%

Formulation Example 2: Gummy
Reduced water tank 40.0wt%
Granulated sugar 20.0
Glucose 20.0
Gelatin 4.7
Water 9.68
Kiwi juice 4.0
Kiwi flavor 0.6
Dye 0.02
Tyrosinase inhibitor 1.0
100.0wt%

Formulation Example 3: Candy
50.0 wt% sugar
Minamata 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
Tyrosinase inhibitor 0.4
100.0wt%

Formulation Example 4: Yogurt (hard / soft)
Milk 41.5wt%
Nonfat dry milk 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Tyrosinase inhibitor 0.4
Perfume
Water residue
100.0wt%

Formulation Example 5: Soft capsule
Kiwi seed oil 87.0wt%
Emulsifier 12.0
Tyrosinase inhibitor 1.0
100.0wt%

Formulation Example 6: Coffee beverage (liquid)
Roasted coffee beans 6.0wt%
Sugar 6.0
Baking soda 0.2
Emulsifier 0.15
Tyrosinase inhibitor 1.0
Water residue
100.0wt%

Formulation Example 7: Coffee drink (powder)
Instant coffee 90.0wt%
Skim milk 7.0
Tyrosinase inhibitor 3.0
100.0wt%

Formulation Example 8: Soft drink
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Tyrosinase inhibitor 0.05
Perfume
Purified water residue
100.0wt%

Formulation Example 9: Tablet
Lactose 54.0wt%
Crystalline cellulose 30.0
Starch degradation product 10.0
Glycerin fatty acid ester 5.0
Tyrosinase inhibitor 1.0
100.0wt%

Formulation Example 10: Tablet
76.4 wt% sugar
Glucose 19.0
Sucrose fatty acid ester 0.2
Tyrosinase inhibitor 0.5
Purified water 3.9
100.0wt%

Formulation Example 11: Cosmetic cream
Squalane 20.0wt%
Beeswax 5.0
Refined jojoba oil 5.0
Glycerin 5.0
Glycerol monostearate 2.0
Polyoxyethylene (20) sorbitan-
Monostearate 2.0
Tyrosinase inhibitor 2.0
Preservative appropriate amount
Perfume
Purified water residue
100.0wt%

Formulation Example 12: lotion
Ethanol 5.0wt%
Glycerin 2.0
1,3-butylene glycol 2.0
Polyethylene oleyl ether 0.5
Sodium citrate 0.1
Citric acid 0.1
Tyrosinase inhibitor 0.1
Purified water residue
100.0wt%

Formulation Example 13: Body gel
Macadamia nut oil 2.0wt%
Octyldodecyl myristate 10.0
Methylphenylpolysiloxane 5.0
Behenyl alcohol 3.0
Stearic acid 3.0
Batyl alcohol 1.0
Glyceryl monostearate 1.0
Tetraoleic acid polyoxyethylene sorbit 2.0
Hydrogenated soybean phospholipid 1.0
Ceramide 0.1
Retinol palmitate 0.1
Preservative appropriate amount
Centella extract 1.0
Tyrosinase inhibitor 1.0
1,3-butylene glycol 5.0
Purified water residue
100.0wt%

Formulation Example 14: Emulsion
Squalane 4.0wt%
Vaseline 2.5
Cetanol 2.0
Glycerin 2.0
Lipophilic glyceryl monostearate 1.0
Stearic acid 1.0
L-Arginine 1.0
Tyrosinase inhibitor 0.5
Potassium hydroxide 0.1
Perfume
Purified water residue
100.0wt%

Formulation Example 15: Bath agent (liquid)
Propylene glycol 50.0wt%
Ethanol 20.0
Sodium sulfate 5.0
Tyrosinase inhibitor 0.5
Lanolin 0.5
Avocado oil 0.5
Dye 1.5
Fragrance 22.0
100.0wt%

Formulation Example 16: Ointment
White beeswax 5.0wt%
Purified lanolin 5.0
Tyrosinase inhibitor 1.0
Fragrance 0.1
Vaseline residue
100 wt%

Formulation Example 17: Cat food
Corn 34.0wt%
Flour 35.0
Meat meal 15.0
Beef tallow 8.9
Salt 1.0
Skipjack extract 4.0
Tyrosinase inhibitor 1.0
Taurine 0.1
Vitamins 0.5
Minerals 0.5
100.0wt%

Formulation Example 18: Dog food
Corn 30.0wt%
Meat (chicken) 15.0
Defatted soybean 10.0
Flour 25.0
Mosses 5.0
Tyrosinase inhibitor 5.0
Animal fats and oils 8.9
Oligosaccharide 0.1
Vitamin 0.5
Mineral 0.5
100.0wt%

  As described above, since the echinacoside has a tyrosinase inhibitory action, it can be used as a whitening agent.

It is a graph which shows the measurement result of the tyrosinase inhibitory effect of a present Example.

Claims (7)

A tyrosinase inhibitor comprising echinacoside as an active ingredient. 2. The tyrosinase inhibitor according to claim 1, wherein the echinacoside is extracted from a plant of the genus Oleaceae. A whitening composition comprising the tyrosinase inhibitor according to claim 1 or 2. A pharmaceutical product for mammals including humans, comprising the whitening composition according to claim 3 as an active ingredient. An external skin preparation for mammals including humans, comprising the whitening composition according to claim 3 as an active ingredient. A food or drink comprising the whitening composition according to claim 3 as an active ingredient. A mammal animal feed comprising the whitening composition according to claim 3 as an active ingredient.