JP2003137801A - Collagen production promoter, collagenase inhibitor, fibroblast cell-propagating agent, skin cosmetic material and food or beverage for cosmetic use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a collagen production promoter having a function for activating the production of the collagen by fibroblast cells, a collagenase inhibitor for inhibiting the collagenase activity associated with the reduction and degeneration of the collagen, a fibroblast cell-propagating agent having activity for propagating the fibroblast cells, a skin cosmetic material having excellent aging prevention and improvement activities, and a food or beverage having a beautifying function obtained by blending such active ingredients. SOLUTION: The collagen production promoter, the collagenase inhibitor and the fibroblast cell-propagating agent containing the collagen production- promoting substance, the collagenase inhibitory substance and the fibroblast cell-propagating substance extracted from Poa eminers Presl., as active ingredients, and the skin cosmetic material and the food or beverage obtained by blending these agents are provided.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a collagen production promoter having an action of activating collagen production by fibroblasts, a collagenase inhibitor which inhibits collagenase activity involved in the reduction / denaturation of collagen, and fibroblasts. The present invention relates to a fibroblast proliferation-promoting agent having the action of proliferating erythrocyte, a skin cosmetic having the action of preventing and improving skin aging, and a cosmetic food and drink having a beauty action, which are prepared by blending these active ingredients.

[0002]

2. Description of the Related Art The epidermis and dermis of skin are composed of epidermal cells, fibroblasts and extracellular matrix such as collagen that is outside these cells and supports the skin structure. Among them, in young skin, water retention, flexibility, and
The elasticity is secured, and the skin is kept firm and shiny in appearance and is kept fresh.

However, when there is an influence of some external factors such as irradiation with ultraviolet rays, remarkable drying of air, excessive skin washing, etc., and aging progresses, collagen, which is a main component of the extracellular matrix, is degraded. The production amount decreases and the elasticity decreases due to crosslinking. As a result, the skin loses its moisturizing function and elasticity, the keratin begins to peel abnormally, and the skin loses its tension and luster, becomes rough, and wrinkles and other aging symptoms.

[0004] Such changes with aging of the skin, that is,
It has been known that wrinkles, dullness, loss of texture, decrease in elasticity, etc. are involved in reduction and denaturation of dermal matrix components such as collagen.

Recently, it has been pointed out that the matrix protease is particularly involved as a factor inducing this change. Among matrix-type proteases, collagenase, that is, MMP-1 (matrix metalloprotease) is known as an enzyme that decomposes type I and III collagens, which are the main constituents of the dermal matrix of the skin, but its expression is exposed to ultraviolet light. Due to
It is considered to be one of the causes of the reduction / denaturation of collagen due to ultraviolet rays, and may be a major factor in the formation of wrinkles on the skin.

Therefore, it is excellent in safety and productivity and can be provided at a low price, and is excellent in preventing aging of the skin.
Although it has been strongly desired to provide a collagenase inhibitor, a collagen production promoting agent, and a fibroblast proliferation-promoting agent having an improving effect, the present situation is that none of them is sufficiently satisfactory.

Under the circumstances, the present invention aims to solve various problems in the prior art and achieve the following objects. The first object of the present invention is to promote collagen production in dermal fibroblasts to prevent skin aging and / or
Another object of the present invention is to provide a collagen production promoter containing, as an active ingredient, a collagen production promoter which can be improved. A second object of the present invention is a collagenase inhibitor containing as an active ingredient a collagenase activity inhibitor capable of suppressing the decrease / denaturation of collagen through inhibiting the collagenase activity and preventing and / or improving skin aging. To provide. A third object of the present invention is to proliferate fibroblasts containing as an active ingredient a fibroblast proliferative substance that can activate and / or improve skin aging by activating fibroblasts through a fibroblast proliferative action. To provide an agent. Further, a fourth object of the present invention is to provide a skin cosmetic having an excellent collagen production promoting action, a collagenase inhibiting action, and a fibroblast proliferation action, which is useful for preventing and / or improving skin aging. Especially. Further, a fifth object of the present invention is to provide a cosmetic food and drink useful in food and drink, which can exert an excellent collagen production promoting action, a collagenase inhibitory action, and a fibroblast proliferation action by eating and drinking, and which is useful for preventing and / or improving skin aging. To provide goods.

[0008]

Means for Solving the Problems As a result of intensive studies to achieve the above-mentioned object, the inventors of the present invention have found that the extract of rosaceae Oni strawberry, especially the leaves, stems, flowers, bark, roots of Oni strawberry. , Seed coat, fruit, fruit kernel, or a mixed portion thereof,
An extract extracted with water or a hydrophilic organic solvent or a mixed solvent thereof, activates collagen production by fibroblasts, inhibits collagenase activity involved in collagen degeneration / denaturation, and fibroblasts It was found that the skin cosmetics and cosmetic foods and drinks containing the extract as an active ingredient have high safety and can prevent and / or improve skin aging, Invented.

Therefore, in order to solve the above-mentioned problems, the present invention provides the following collagen production promoter, collagenase inhibitor, fibroblast proliferation agent, skin cosmetics and cosmetic food and drink.

[0010] The invention of claim 1 is a collagen production promoting agent comprising a collagen production promoting substance extracted from Oni strawberry of the Rosaceae family as an active ingredient.
In the invention of claim 2, the leaves, stems, flowers, bark, roots, seed coats, fruits, fruit kernels, or a mixed portion thereof of Oni strawberry,
The collagen production promoter according to claim 1, which comprises, as an active ingredient, a collagen production promoter obtained by extraction with water, a hydrophilic organic solvent, or a mixed solvent thereof. A third aspect of the present invention is a collagenase inhibitor, which comprises a collagenase activity inhibitor extracted from Oni strawberry of the Rosaceae family as an active ingredient. In the invention of claim 4, the leaves, stems, flowers, bark, roots, seed coats, fruits, fruit kernels, or a mixed portion thereof are extracted with water or a hydrophilic organic solvent or a mixed solvent thereof. The collagenase inhibitor according to claim 3, comprising the obtained collagenase activity inhibitor as an active ingredient. A fifth aspect of the present invention is a fibroblast proliferation agent, which comprises a fibroblast proliferation substance extracted from Oni strawberry of the Rosaceae family as an active ingredient. In the invention of claim 6, the leaf part, stem part, flower part, bark, root part, seed coat, fruit, fruit kernel or a mixed portion thereof is extracted with water or a hydrophilic organic solvent or a mixed solvent thereof. The fibroblast proliferation agent according to claim 5, which comprises the obtained fibroblast proliferation agent as an active ingredient. A seventh aspect of the present invention is a skin cosmetic comprising the active ingredient according to any one of the first to sixth aspects. The invention of claim 8 further comprises one or more whitening agents selected from the group consisting of ascorbic acid and its derivatives, placenta extract, kojic acid, rucinol, arbutin, ellagic acid and chamomile extract. The skin cosmetic composition according to item 7. The invention of claim 9 is any one of claims 1 to 6.
It is a food and drink product for beauty treatment, characterized in that it contains the active ingredient according to item.

[0011] In addition, although the fruits of the rosaceae Oni strawberry are edible, the extract of Oni strawberry has excellent collagen production promoting action, collagenase inhibitory action, and fibroblast proliferation action, and prevents skin aging and It is not known at all to be useful for improvement, and / or these are new findings of the present inventors.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in more detail below. The collagen production-promoting agent, collagenase inhibitor, and fibroblast proliferation-promoting agent of the present invention contain the collagen production-promoting substance, collagenase activity-inhibiting substance, and fibroblast proliferation-promoting substance extracted from Oni strawberry as active ingredients.

Here, oni strawberry (scientific name: Rubus)
Ellipticus (Chinese name: truncated lance) belongs to the family Rosaceae, and fresh fruits are fragrant and edible.
Oni strawberry is native or cultivated in the Southeast Asia and Southeastern China from the Himalayas, and can be easily obtained from these areas.

The constituent parts of the Oni strawberry used as the extraction raw material are not particularly limited, and for example, leaves, stems, flowers, bark, roots, seed coats, fruits, fruit kernels or mixed portions thereof are used as the extraction raw materials. Although it can be used, it is preferable to use the root part as an extraction raw material among these.

The root of the strawberry, which is the raw material for extraction, is
It is suitable to dry and crush immediately after collection. Drying may be performed in the sun or using a commonly used dryer. Oni strawberry may be used as an extraction raw material after pretreatment such as degreasing with a non-polar solvent such as hexane or benzene. By performing a pretreatment such as defatting, the extraction treatment of Oni strawberry with the extraction solvent can be efficiently performed.

As the extraction solvent, it is preferable to use water, a hydrophilic organic solvent or a mixed solvent thereof. Specific examples of suitable extraction solvents include water, lower aliphatic alcohols, hydrous lower aliphatic alcohols, and the like, and these can be used alone or as a mixture of two or more thereof. Specific examples of suitable lower aliphatic alcohols include methanol, ethanol, propanol, 1,3-butylene glycol, glycerin, propylene glycol and the like.

Water that can be used as the extraction solvent includes pure water,
In addition to tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, those that have been subjected to various treatments are included. Examples of the treatment applied to water include purification, heating, sterilization, sterilization,
It includes filtration, ion exchange, adjustment of osmotic pressure, buffering, etc. Therefore, the water that can be used as the extraction solvent in the present invention also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline and the like.

When a mixed solvent of two or more hydrophilic organic solvents is used as the extraction solvent, the mixing ratio can be adjusted appropriately. For example, when a mixed liquid of water and lower aliphatic alcohol is used, the mixing ratio of water and lower aliphatic alcohol can be 7: 3 to 2: 8 (mass ratio).

The extraction treatment is not particularly limited as long as the soluble component contained in the strawberry can be eluted in the extraction solvent, and can be performed according to a conventional method. At the time of the extraction treatment, it is not necessary to employ a special extraction method, and any device can be used at room temperature or under reflux heating.

For example, the extraction raw material is put into a treatment tank filled with the extraction solvent, and the soluble components are eluted with stirring occasionally. At this time, the extraction conditions may be appropriately adjusted depending on the extraction raw material and the like, but the extraction solvent amount is usually 5 to 15 times the extraction raw material amount (mass ratio), the extraction time is usually 1 to 3 hours, The extraction temperature is usually room temperature to about 95 ° C.

After the soluble component is eluted by the extraction treatment, the extract residue is removed by filtration to obtain an extract. The obtained extract is a diluted or concentrated solution of the extract, a dried product of the extract, or a crude product or a purified product thereof, diluted according to a conventional method,
You may perform processes, such as concentration, drying, and refinement | purification.

The obtained extract can be used as it is as a collagen production promoter, a collagenase inhibitor, and a fibroblast proliferation agent, but a concentrated solution or a dried product thereof is easier to use. When obtaining a dried product of the extract, a carrier such as dextrin or cyclodextrin may be added to improve hygroscopicity.

Since the extract of Oni strawberry has a peculiar odor and taste, it can be purified for the purpose of decolorization, deodorization, etc. within a range that does not impair its physiological activity. Since it is not used in large quantities when added to skin cosmetics and beauty foods and drinks, there is no practical problem even if it remains unpurified. The purification can be carried out by, for example, activated carbon treatment, adsorption resin treatment, ion exchange resin treatment or the like.

The Oni strawberry extract thus obtained has a collagen production promoting action, a collagenase inhibiting action and a fibroblast proliferation action. Although the Oni strawberry extract can be used as it is as a collagen production promoter, a collagenase inhibitor, and a fibroblast proliferation agent, it can be provided in the form of a pharmaceutical preparation according to a conventional method. In the case of formulation, a pharmaceutically acceptable carrier such as dextrin or cyclodextrin, or any other auxiliaries can be added to facilitate storage and handling. The extract from Oni strawberry can be made into any dosage form such as powder, granules and tablets by formulation.

<Skin cosmetics> The collagen production-promoting agent, collagenase inhibitor and fibroblast growth-promoting agent of the present invention can prevent and / or improve aging of the skin and provide a feeling of use when applied to the skin. Since it is excellent in safety, it is suitable for incorporation into skin cosmetics. The skin cosmetic may contain one kind of collagen production promoter, collagenase inhibitor and fibroblast proliferation agent, or two or more kinds in combination.
In this case, the amount of the collagen production-promoting agent, collagenase inhibitor and fibroblast proliferation-acting agent of the present invention can be appropriately adjusted depending on the type of skin cosmetics, physiological activity of the extract, etc. The rate is about 0.01 to 1 with respect to the total skin cosmetics, converted to the standard Oni strawberry extract.
It is 0 mass%.

The skin cosmetic of the present invention preferably further contains a whitening agent in an amount of 0.01 to 10% by mass, particularly 0.1 to 5% by mass, based on the entire skin cosmetic.

Examples of the whitening agent include ascorbic acid or its derivative, sulfur, placenta hydrolyzate, ellagic acid or its derivative, kojic acid or its derivative, glucosamine or its derivative, arbutin or its derivative, hydroxycinnamic acid or Derivatives thereof, glutathione, arnica extract, sardine extract, sow extract, psycho extract, sardine extract, Ganoderma lucidum mycelium culture or extract thereof, linden extract, peach leaf extract, ages extract, kujin extract, soybean extract, touki extract,
Yokuinin extract, oyster leaf extract, rhubarb extract, button pipi extract, hamamelis extract, horse chestnut extract, Hypericum perforatum extract, oil-soluble licorice extract (liquorice hydrophobic flavone, glabridin, grabrene, lycochalcone A) and the like, and one of these may be used alone. Or two or more kinds can be used in combination. Among these, in the skin cosmetic of the present invention, from the viewpoint of improving the whitening effect, ascorbic acid or a derivative thereof, placenta extract, chamomile extract, arbutin, ellagic acid,
It is preferable to use one kind or two or more kinds selected from rucinol and kojic acid.

In the skin cosmetic of the present invention, the collagen production promoter, the collagenase inhibitor, the fibroblast proliferation agent, and the whitening agent which can be used as constituents are not particularly limited, but they are astringent agents. , Sterilization
Antibacterial agents, UV absorbers, humectants, cell activators, anti-inflammatory / anti-allergic agents, antioxidants / active oxygen scavengers, oils and fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants , Fragrance, etc. are used. These constituents may act synergistically when used in combination with the above-mentioned Oni strawberry extract to bring about an excellent use effect more than normally expected.

Examples of the astringents include citric acid or salts thereof, tartaric acid or salts thereof, lactic acid or salts thereof,
Aluminum chloride, aluminum sulfate / potassium sulfate, allantoin chlorohydroxyaluminum, allantoin dihydroxyaluminum, zinc paraphenol sulfonate, zinc sulphate, juniper extract, age extract, hamamelis extract, gem ginger extract, chacatechins,
Odorikosu extract, Hypericum extract, Rheum palmatum extract, Cornflower extract, Ivy extract, Cucumber extract, Horse chestnut extract, Salvia extract, Melissa extract, etc. are mentioned, and one of these may be used alone or 2
A combination of two or more species can be used.

Examples of the bactericidal / antibacterial agents include benzoic acid, sodium benzoate, paraoxybenzoic acid ester, distearylmethylammonium chloride, benzethonium chloride, chlorhexidine hydrochloride, photosensitizer 101, photosensitizer 201, salicylic acid, salicylic acid. Sodium, sorbic acid, halocarban, resorcin, parachlorophenol, phenoxyethanol, bisabolol, hinokitiol, menthol, chitosan, degradation products of chitosan, diyu extract, kujin extract, nematophor extract, loquat extract, yucca extract, aloe extract, cinnamon extract, gauze extract, etc. These may be used alone or in combination of two or more.

Examples of the ultraviolet absorber include β-
Isopropylfuranone derivative, urocanic acid, ethyl urocanate, oxybenzone, oxybenzone sulfonic acid, tetrahydroxybenzophenone, dihydroxydimethoxybenzophenone, dihydroxybenzophenone, synoxate, methyl diisopropylcinnamate, octyl methoxycinnamate, glyceryl paraaminobenzoate, paradimethylaminobenzoic acid Amyl, octyl paradimethyl benzoate, paraaminobenzoic acid, ethyl paraaminobenzoate, titanium oxide, β-carotene, γ-oryzanol, rice bran extract, aloe extract, birch extract, birch extract, chamomile extract, henna extract, butterfly ginger extract, ginkgo biloba. Leaf extract, chamomile extract, hawthorn extract, oil-soluble licorice extract, etc. These 1 type can be used individually or in combination of 2 or more types.

Examples of the moisturizers include serine, glycine, threonine, alanine, collagen, hydrolyzed collagen, hydronectin, fibronectin, keratin, elastin, royal jelly, chondroitin sulfate heparin, glycerophospholipid, glyceroglycolipid, sphingophospholipid. , Glycosphingolipids, linoleic acid or its esters, eicosapentaenoic acid or its esters, pectin, bifidobacteria fermented product, lactic acid fermentation product, yeast extract, litchi mycelium culture or its extract, wheat germ oil, avocado Oil, rice germ oil, jojoba oil, soybean phospholipids, γ-oryzanol, velvet aoi extract, Yokuinin extract, dio extract, tannin extract, tannin extract, kidachi aloe extract, burdock extract, mannen wax extract, arnica Kiss, wheat bran and the like, may be used these alone or in combination of two or more.

Examples of the cell activating agent include riboflavin or its derivative, pyridoxine or its derivative,
Nicotinic acid or a derivative thereof, pantothenic acid or a derivative thereof, α-tocopherol or a derivative thereof, arnica extract, carrot extract, rapeseed ginseng extract, loofah extract (saponin), shikon extract, oak extract, button pie extract, peony extract, mukurodi extract, safflower Extracts, ashitaba extract, loquat leaf extract, Hiki-Oshi extract, Yukinoshita extract, yellow-eye extract, salvia extract, garlic extract, mannen wax extract and the like can be used, and one of these can be used alone or in combination of two or more. .

Examples of the anti-inflammatory / anti-allergic agents include azulene, allantoin, aminocaproic acid, indomethacin, lysozyme chloride, epsilon aminocaproic acid, oxybenzone, glycyrrhizic acid or its derivative, glycyrrhetinic acid or its derivative, and photosensitizer 301.
No., Photosensitizer No. 401, diphenhydramine hydrochloride, tranexamic acid or its derivative, adenosine phosphate, estradiol, estrone, ethinyl estradiol, cortisone, hydrocortisone, prednisone, progesterone, corticosterone, arnica extract, inchinko extract, sanshishi extract, deer yak. Examples of the extract include licorice extract, citrus extract, mugwort extract, oleander extract, gentian extract, psychological extract, senkyu extract, yarrow extract, laurel extract, and perilla extract, and one of these may be used alone or 2
A combination of two or more species can be used.

Examples of the antioxidant / active oxygen scavenger include dibutylhydroxytoluene, butylhydroxyanisole, propyl gallate, baicalin, baicalein, superoxide dismutase, catalase, rosemary extract, melissa extract, sardine extract, Age extract, loquat leaf extract, hop extract,
Hamamelis extract, peony extract, sage extract,
Cina extract, chamomile extract, eucalyptus extract, perilla extract, ginkgo biloba extract, thyme extract, cardamom extract, caraway extract, nutmeg extract, mace extract, laurel extract, clove extract, turmeric extract, willow tree extract, etc.
The seeds may be used alone or in combination of two or more.

Examples of the oils and fats include soybean oil, linseed oil, sesame oil, bran oil, cottonseed oil, rapeseed oil, safflower oil, corn oil, olive oil, camellia oil, almond oil, castor oil, peanut oil, cocoa oil. , Palm kernel oil,
Beef tallow, mink oil, jojoba oil, evening primrose oil, horse oil, etc. are mentioned, and these 1 type can be used individually or in combination of 2 or more types.

Examples of the waxes include carnauba wax, candelilla wax, beeswax, honey bees wax, spermaceti wax, cerax, lanolins, and the like, and one kind of them may be used alone or in combination of two or more kinds. Can be used.

Examples of the hydrocarbons include liquid paraffin, petrolatum, micro-thristalin wax,
Ceresin, squalane, polyethylene powder and the like can be mentioned, and one of these can be used alone or in combination of two or more.

Examples of the fatty acids include stearic acid, linoleic acid, lauric acid, myristic acid, palmitic acid, hevenic acid, lanolinic acid, oleic acid, undecylenic acid and isostearic acid. They can be used alone or in combination of two or more.

Examples of the alcohols include lauryl alcohol, cetyl alcohol, stearyl alcohol, lanolin alcohol, hydrogenated lanolin alcohol,
Oleyl alcohol, hexadecyl alcohol, 2-octyldodecanol, glycerin, sorbitol, propylene glycol, 1,3-butylene glycol, ethylene glycol or a polymer thereof, glucose, sucrose, cholesterol, phytosterol, cetostearyl alcohol and the like, These 1 type can be used individually or in combination of 2 or more types.

Examples of the esters include decyl oleate, butyl stearate, myristyl myristate, hexyl laurate, isopropyl palmitate, isopropyl myristate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, and propylene glycol dioleate. , Diethyl phthalate, glyceryl monostearate, glyceryl trimyristate, cetyl lactate and the like, and one of these may be used alone or two or more thereof may be used in combination.

As the above-mentioned surfactant, nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants and the like can be used, among which no skin disease occurs, or Surfactants listed on the basis of minor cosmetic ingredients are preferred. For example, soybean lecithin, egg yolk lecithin, saponin, oligoglycoside, phospholipid biosurfactant, acyl peptide biosurfactant, polyoxyethylene polyoxypropylene glycol, polyoxyethylene polyoxypropylene cetyl ether, polyoxyethylene polyoxypropylene. Butyl ether, polyoxyethylene coconut oil fatty acid monoethanolamide, polyoxyethylene lauryl ether, polyoxyethylene lauryl ether sulfate triethanolamine, sodium polyoxyethylene lauryl ether sulfate, polyoxyethylene lauryl ether phosphate, polyoxyethylene lauryl ether phosphorus Sodium acid, polyoxyethylene lanolin, polyoxyethylene lanolin alcohol, polyoxypropionate Down-butyl ether, polyvinyl alcohol, polyvinyl pyrrolidone, sodium polyphosphate, sorbitan monooleate, polyethylene glycol monooleate,
Polyoxyethylene sorbitan monooleate, ethylene glycol monostearate, sorbitan monostearate, propylene glycol monostearate, polyethylene glycol monostearate, polyoxyethylene glyceryl monostearate, polyoxyethylene sorbitan monostearate, monopalmitic acid Surfactants such as sorbitan, polyoxyethylene sorbitan monopalmitate, sorbitan monolaurate, polyethylene glycol monolaurate, polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitol monolaurate, and coconut oil fatty acid diethanolamide can be mentioned. The seeds may be used alone or in combination of two or more.

Examples of the fragrance include menthol,
Carvone, eugenol, anethole, peppermint oil, spearmint oil, peppermint oil, eucalyptus oil, anise oil and the like can be mentioned, and one of these can be used alone or in combination of two or more.

The skin cosmetic of the present invention has an excellent effect of preventing and / or improving skin aging. For example, ointment, cream, emulsion, lotion, lotion, pack, lipstick, lip balm. It can be widely used for bath salts and the like.

<Beauty Foods and Beverages> It has been confirmed that the active ingredients of the collagen production-promoting agent, collagenase inhibitor and fibroblast growth-promoting agent of the present invention are not those that are digested in the digestive tract. , Can be added to any food or drink or dietary supplement. In this case, in particular, the collagen production-promoting agent, the collagenase inhibitor and the fibroblast proliferation-promoting agent of the present invention can prevent and / or improve skin aging through their respective actions, and are therefore incorporated into cosmetic foods and drinks. It is suitable for Here, in the present invention, “food and drink for beauty use” means food and drink for the purpose of preventing and improving aging of beautiful skin or skin.

The cosmetic food and drink of the present invention may be the food and drink containing the collagen production promoter, collagenase inhibitor and fibroblast proliferation-promoting agent of the present invention in any food and drink that does not interfere with its activity. Alternatively, it may be a granular or tablet nutritional supplement containing the collagen production promoter, the collagenase inhibitor and the fibroblast proliferation agent of the present invention as the main components.

When a cosmetic food or drink is produced by adding the collagen production promoter, the collagenase inhibitor and the fibroblast growth-promoting agent of the present invention, sugars such as dextrin and starch; gelatin, soybean protein, Protein such as corn protein; amino acids such as alanine, glutamine, isoleucine; polysaccharides such as cellulose and gum arabic; soybean oil, medium chain fatty acid triglyceride, and other optional additives such as fats and oils Can be formulated into

The amount of the collagen production promoter, collagenase inhibitor and fibroblast growth-promoting agent blended in the cosmetic food and drink of the present invention is such that the daily intake of adult honey strawberries is taken into consideration in consideration of the general intake of the food and drink to be added. It is preferable to adjust the intake of the product to about 1 to 1000 mg per day.

The beauty food and drink is not particularly limited, but specific examples thereof include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks (including concentrated liquids and adjustment powders of these drinks. ); Ice cream, ice sorbet, shaved ice, and other frozen desserts; buckwheat noodles such as noodles such as buckwheat noodles, udon, harusame, gyoza skin, Shumai skin, Chinese noodles, instant noodles; candy, candy, gum, chocolate, snacks, biscuits, jellies, Confectioneries such as jams, creams, baked goods; processed fish and livestock products such as kamaboko, ham, sausages; dairy products such as processed milk and fermented milk; salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing, etc. Oils and fats and oil processed foods; seasonings such as sauces and sauces; various forms of health such as tablets and granules And nutritional supplements such; Other soup,
It can be added to stews, salads, side dishes, pickles and the like.

The collagen production-promoting agent, collagenase inhibitor, fibroblast-proliferating agent, skin cosmetics and cosmetic food and drink of the present invention are preferably applied to humans. It can also be applied to animals other than humans as long as the action and effect are exhibited.

[0051]

EXAMPLES The present invention will be described more specifically below by showing production examples, examples and comparative examples, but the present invention is not limited to these examples.

[Manufacturing Example 1] 300 g of coarsely crushed root of Oni strawberry were mixed with 2000 mL of four kinds of extraction solvents shown in Table 1.
The mixture was placed in a flask and maintained at 70 ° C for 3 hours with gentle stirring, then filtered, and the filtrate was concentrated under reduced pressure at 40 ° C and further dried in a reduced pressure dryer to obtain a root extract of strawberry. It was
The yield of the extract was as shown in Table 1. When the extraction solvent is a mixture, the mixing ratios shown below are based on mass.

[0053]

[Table 1]

[Production Example 2] 300 g of the same coarsely pulverized Oni strawberry root used in Production Example 1 was added to 2000 mL of the three kinds of extraction solvents shown in Table 2, and stirred at 80 ° C.
After being kept for 3 hours, the mixture was filtered to obtain about 1500 mL of the extract having the solid content concentration shown in Table 2. When the extraction solvent is a mixture, the mixing ratios shown below are based on mass.

[0055]

[Table 2]

Example 1 Collagen production promoting action
Test Sample No. obtained in Production Examples 1 and 2. The extracts 1 to 7 were tested for their collagen production promoting action. Specifically, the test was conducted as follows.

First, 96 wells of human fibroblasts were used.
Seeding in a plate, 37 ° C., 5% CO ₂ -95% ai
90 μL of supernatant after culturing for several days in each sample-added medium (sample concentration: 25 ppm or 12.5 ppm) under r
To ELISA plate, 4 ℃, over
After adsorbing to the plate at night, discard the solution,
Washing was performed with a phosphate physiological buffer solution (PBS-T) containing 0.05% Tween-20. After that, a blocking operation was performed with a physiological phosphate buffer containing 1% bovine serum albumin. Discard the solution and remove 0.05% Tween
Washing was performed with a physiological phosphate buffer solution (PBS-T) containing -20, and an anti-human collagen type I antibody (rabbit Ig
G; manufactured by Chemicon) was reacted. Discard the solution, 0.0
Phosphate physiological buffer (PB containing 5% Tween-20)
S-T), wash and HRP-labeled anti-rabbit IgG
After reacting with the antibody, the same washing operation was performed to carry out the color reaction. The collagen production promoting rate was calculated by performing the above-mentioned ELISA using a standard product, preparing a calibration curve, and setting the collagen production amount when the sample was not added as 100%. Table 3 shows the collagen production promotion rate (%) of each sample. When the sample is the extract according to Production Example 2, the “sample concentration” is the concentration in terms of solid content.

[0058]

[Table 3] From the results shown in Table 3, it was confirmed that the extract from the root of the strawberry has a function of promoting collagen production of fibroblasts. Further, the strength of the collagen production promoting action of the Oni strawberry root extract changes depending on the concentration of the Oni strawberry root extract, and the strength of the collagen production promoting action is adjusted by adjusting the concentration of the Oni strawberry root extract. It was confirmed that it was possible.

Example 2 Test of Collagenase Inhibitory Action
Test Sample Nos. Obtained in Production Examples 1 and 2 1-7 extracts were tested for collagenase inhibitory effect. Specifically, the test was conducted as follows.

First, each sample solution (solvent: 20 mmol /
50 μL of 0.1 mol / L Tris-HCl buffer (pH 7.1) containing L calcium chloride, 50 μL of collagenase solution and 400 μL of substrate solution were mixed and incubated at 37 ° C. for 30 minutes. Then 25mmo
The reaction was stopped with 1 mL of a 1 / L citric acid solution, and the mixture was extracted with 5 mL of ethyl acetate. The wavelength of the obtained extract is 32
The absorbance at 0 nm (control solution: ethyl acetate) was measured. The same enzyme reaction and absorbance measurement as above were performed by adding the same amount of the buffer solution as the sample solution instead of the sample solution. Furthermore, in each case, the same operation and measurement were performed by adding the buffer solution instead of the collagenase solution. The collagenase solution is Collagenase Type from Sigma.
e IV (5 mg) was dissolved in the buffer (1 mL) and diluted 50 times before use. As a substrate solution, BACHEM Fenichemikali was added to the buffer solution.
En AG Pz-peptide concentration is 0.5 mol / L
It was used by dissolving so that

From the measurement results, the collagenase inhibition rate was calculated by the following formula. <Equation 1> Collagenase inhibition rate (%) = [1− (AB) / (C−
D)] × 100 where A: Absorbance when sample solution is added, enzyme is added B: Absorbance when sample solution is added, and enzyme is not added C: Absorbance when sample is not added, enzyme is not added D: Sample is not added, enzyme is not added Absorbance at time

The above-mentioned inhibition rate was measured by gradually decreasing the sample concentration, and the concentration of the sample solution that inhibits the activity of collagenase by 50% was determined by the interpolation method. The results are shown in Table 4.
If the 50% inhibitory concentration of collagenase is 400 ppm or less, it can be judged that the collagenase inhibitory activity is sufficient.

[0063]

[Table 4] From the results shown in Table 4, it was confirmed that the extract from the root of Oni strawberry had a collagenase inhibitory action. Further, the strength of the collagenase inhibitory action of such Oni strawberry root extract changes depending on the concentration of Oni strawberry root extract, it is possible to adjust the strength of collagenase inhibitory action by adjusting the concentration of Oni strawberry root extract. confirmed.

Example 3 Test for Proliferative Action of Fibroblasts Sample No. 1 obtained in Production Examples 1 and 2 The fibroblast proliferation effect of the extracts 1 to 7 was measured by the MTT method (J. Immu).
nol. Tested according to Method 93, 157, 1986). Specifically, the test was conducted as follows.

First, a 10% FBS-containing medium (α-MEM medium: GIBCO) placed in a 25 cm ² culture flask.
1 × 10 ⁶ human normal neonatal dermal fibroblasts (NB1RGB) were seeded on a BLR product, pH 7.2), and 37
Cultivation was carried out at 5 ° C. under 5% CO ₂ -95% air for 4 days.
The cells were then trypsinized and centrifuged to collect cells. The cells obtained as a precipitate were added to a medium containing 5% FBS (α
-MEM medium: GIBCO BLR product, pH 7.
Suspend in 2), 7 per 96 well plate
× 10 ³ pieces were dispensed. After culturing for 24 hours, 100 μL of 5% FBS-containing medium in which the sample was dissolved was added per well, and the cells were cultured at 37 ° C. under 5% CO ₂ -95% air for 3 days. After culturing, 100 μL of the medium was removed per well, and the MTT reagent (3- (4,5-dimethyl-2
-Thiazolyl) -2,5-diphenyl-
2H tetrazolium bromide, 5mg
/ ML PBS (-) solution) 20 μL, and add
Incubated for an hour (reactive oxygen from mitochondria in the grown cells reacts with the MTT reagent, and the color of the reagent that was yellow changes to blue-yellow with an absorption peak at 570 nm). Thereafter, 100% by mass of sodium dodecyl sulfate-0.01 mol / L sulfuric acid solution was added to each hole.
Each μL was dispensed and incubated for 18 hours. After the incubation was completed, the absorbance at 570 nm was measured using a microplate reader. Separately, a blank was taken with only the sample, and the same operation was performed to measure the absorbance. In addition, each measured absorbance was 65 measured at the same time.
The 0 nm absorbance was subtracted to correct for the effect of turbidity due to grown cells. From each corrected absorbance, the cell growth promoting rate was calculated by the following formula.

<Equation 2> Cell growth promoting rate (%) = [(AC)-(BD)] /
(BD) × 100 where A: absorbance when sample is added B: absorbance when sample is not added C: absorbance when sample is added, cells are not added D: absorbance when sample is not added, cells are not added

Next, the sample concentration is 400 ppm and 200 p.
The fibroblast proliferation effect was tested by measuring the cell proliferation promoting rate with pm and 100 ppm gradually reduced. The results are shown in Table 5.

[0068]

[Table 5] From the results in Table 5, it was confirmed that the extract from the root of the strawberry had a fibroblast proliferation effect. Further, the strength of the fibroblast proliferation action of such Oni strawberry root extract changes depending on the concentration of the Oni strawberry root extract, and the strength of the fibroblast proliferation action is adjusted by adjusting the concentration of the Oni strawberry root extract. Was confirmed to be adjustable.

[Example 4] Wrinkle improving action (aging of skin )
(Prevention / improvement effect) test Sample No. 1 of Production Example 1 A milky lotion (hereinafter, referred to as "the milky lotion of the present invention") having the following composition containing the 50% ethanol extract of Oni strawberry root of No. 2 was prepared by a conventional method. Oni strawberry root extract (Sample No. 2 of Production Example 1) 0.1 g Cetyl alcohol 0.5 g Beeswax 2.0 g Polyoxyethylene sorbitan oleate (10 EO) 1.0 g Glyceryl monostearate 1.0 g Hyaluronic acid 0 1 g Propylene glycol 5.0 g Ethanol 3.0 g Methyl paraoxybenzoate 0.3 g Perfume 0.03 g Purified water balance (total volume is 100 mL)

The following evaluation test was carried out using the emulsion of the present invention and a comparative emulsion having the same composition as the emulsion of the present invention except that it did not contain the extract of Oni strawberry root. <Evaluation test> From a large number of women aged 22 to 51,
The cuticles disappear, wide areas of keratin are turned over, or skin grooves
Twenty people who were judged to have rough skin, such as unclear cuticles and partial keratinization, were selected as test subjects. To each test subject, the emulsion of the present invention was applied to the right half of the face, and the comparative emulsion was applied to the left half once each morning and evening for 30 days, and the following judgment 1 and judgment 2 were performed.

[Judgment 1: Wrinkle improving effect] After completion of the coating test,
Sylflo (FLEXDEVELOPMENTS
A replica of the face is taken using the replica method by LTD., A photograph of each replica is taken, the image is captured by a scanner, and image processing software (Adobe Photos) is used.
hop ^(R) 5.0) to prepare a histogram of each replica. Observe the condition of wrinkles on the skin,
The evaluation criteria shown in Table 6 were used. The judgment results are shown in Table 7.

[0072]

[Table 6]

[0073]

[Table 7] From the results shown in Table 7, the wrinkles were remarkably improved in the area coated with the emulsion of the present invention as compared with the area coated with the comparative emulsion.

[Judgment 2-Sensory Evaluation] Regarding the feeling of use and the effect on the skin, all subjects were asked about the superiority or inferiority of the emulsion of the present invention and the comparative emulsion. Table 8 shows the results of collecting the answers.

[0075]

[Table 8] From the results of Table 8, it was confirmed by sensory evaluation that the same effects as those of the above-mentioned determination 1 and excellent usability were obtained.

Therefore, from the results of Judgment 1 and 2, the skin cosmetic containing the extract of Oni strawberry root prevents skin aging.
It was confirmed that it has an improving effect (a rough skin improving effect), and is excellent in the feeling of use and safety when applied to the skin.

Example 5 Emulsion An emulsion having the following composition was produced by a conventional method. Jojoba oil 4 g Olive oil 2 g Squalane 2 g Cetanol 2 g Glyceryl monostearate 2 g Polyoxyethylene cetyl ether (20 EO) 2.5 g Polyoxyethylene sorbitan oleate (20 EO) 2 g 1,3-butylene glycol 3 g Paraoxybenzoic acid Methyl 0.15g Magnesium ascorbate phosphate 0.1g Yellow mucous extract 0.1g Ginkgo biloba extract 0.1g Conchiolin 0.1g Oat extract 0.1g Chamomile extract 0.1g Dipotassium glycyrrhizinate 0.1g Perfume 0.05g Oni strawberry root Extract (Sample No. 3 of Production Example 1) 0.1 g Onion strawberry root extract (Sample No. 5 of Production Example 2) 1 g Purified water balance (total amount is 100 g)

[Example 6] Lotion A lotion having the following composition was produced by a conventional method. Glycerin 3 g 1,3-butylene glycol 3 g Polyoxyethylene sorbitan oleate (20 EO) 0.5 g Methyl paraoxybenzoate 0.15 g Citric acid 0.1 g Sodium citrate 0.1 g Oil-soluble licorice extract 0.1 g Seaweed extract 0.1 g Xylobiose mixture 0.5 g Kujin extract 0.1 g Perfume 0.05 g Oni strawberry root extract (Sample No. 1 of Production Example 1) 0.2 g Oni strawberry root extract (Sample No. 5 of Production Example 2) 2 g Purified water balance (total amount is 100 g)

Example 7 Cream A cream having the following composition was produced by a conventional method. Liquid paraffin 5 g Salix beeswax 4 g Cetanol 3 g Squalane 10 g Lanolin 2 g Stearic acid 1 g Polyoxyethylene sorbitan oleate (20 EO) 1.5 g Glyceryl monostearate 3 g 1,3-Butylene glycol 6 g Methyl paraoxybenzoate 1.5 g Retinoic acid 0.1 g Yeast extract 0.1 g Perilla extract 0.1 g Cinnabar extract 0.1 g Chinese cabbage extract 0.1 g Perfume 0.1 g Oni strawberry root extract (Sample No. 3 in Production Example 1) 0.1 g Oni strawberry root Extract (Sample No. 5 of Production Example 2) 1 g Purified water Remainder (total amount is 100 g)

Example 8 Pack A pack having the following composition was produced by a conventional method. Polyvinyl alcohol 15 g Polyethylene glycol 3 g Propylene glycol 7 g Ethanol 10 g Ethyl paraoxybenzoate 0.05 g Tocopherol acetate 0.1 g Sage extract 0.1 g Touki extract 0.1 g Carrot extract 0.1 g Perfume 0.05 g Onion strawberry root extract ( Sample No. 5 of Production Example 2) 5 g purified water balance (total amount is 100 g)

Example 9 Tablet Dietary Supplement The following mixture was tabletted to give a tablet dietary supplement. Oni strawberry root extract (Sample No. 2 of Production Example 1) 50 parts by mass Powdered sugar (sucrose) 188 parts by mass Glycerin fatty acid ester 12 parts by mass

Example 10 Granular Dietary Supplement The following mixture was formed into granules to give a granular dietary supplement. Oni strawberry root extract (Sample No. 1 of Production Example 1) 34 parts by mass Beet oligosaccharide 1000 parts by mass Vitamin C 167 parts by mass Stevia extract 10 parts by mass

The skin cosmetics and cosmetic foods and drinks of Examples 5 to 10 can exhibit excellent collagen production promoting action, collagenase inhibiting action, and fibroblast proliferation action, and prevent skin aging and / or It was useful for improvement.

[0084]

As described above, according to the present invention,
It is possible to provide a collagen production-promoting agent containing, as an active ingredient, a collagen production-promoting substance capable of promoting the production of collagen in dermal fibroblasts and preventing and / or improving skin aging. Further, according to the present invention, there is provided a collagenase inhibitor containing, as an active ingredient, collagenase activity inhibition capable of suppressing collagen depletion / denaturation by inhibiting collagenase activity and preventing and / or improving skin aging. be able to. Further, according to the present invention, a fibroblast proliferation agent containing a fibroblast proliferation substance as an active ingredient, which activates fibroblasts through a fibroblast proliferation action, and can prevent and / or improve skin aging. Can be provided. Further, according to the present invention, it is possible to provide a skin cosmetic having an excellent collagen production promoting action, a collagenase inhibiting action, and a fibroblast proliferation action, which is useful for preventing and / or improving skin aging. . Further, according to the present invention, there is provided a cosmetic food and drink product which can exert excellent collagen production promoting action, collagenase inhibitory action, and fibroblast proliferation action by eating and drinking, and which is useful for preventing and / or improving skin aging. can do.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 7/00 A61K 7/00 K 7/48 7/48 A61P 17/16 A61P 17/16 43/00 111 43/00 111 (72) Inventor Naoko Kishida 1089-8 Aikata, Shinichi-machi, Ashina-gun, Hiroshima Prefecture Maruzen Pharmaceutical Co., Ltd. Research Institute (72) Yoshihito Kawashima 1089-8, Aimachi-machi, Ashina-gun, Hiroshima Prefecture Maruzen Pharmaceutical Co., Ltd. company Research Institute in the F-term (reference) 4B018 MD52 ME14 MF01 MF06 4C083 AA032 AA071 AA082 AA111 AA112 AA122 AC022 AC072 AC102 AC122 AC182 AC242 AC302 AC311 AC422 AC442 AC482 AC841 AD042 AD112 AD332 AD411 AD412 AD512 AD532 AD622 AD641 AD642 AD662 CC02 CC04 CC05 CC07 DD31 EE12 4C088 AB51 AC03 AC04 AC05 AC06 AC11 BA08 BA09 CA04 CA05 MA02 MA03 MA07 MA08 MA17 MA28 MA63 NA14 ZA89 ZC20

Claims (9)

[Claims] 1. A collagen production-promoting agent, which comprises a collagen production-promoting substance extracted from Oni strawberry of the Rosaceae family as an active ingredient. 2. The leaves, stems, flowers, bark of strawberry,
The collagen production promotion according to claim 1, which comprises as an active ingredient a collagen production promoting substance obtained by extracting the root, seed coat, fruit, fruit nucleus or a mixed site thereof with water or a hydrophilic organic solvent or a mixed solvent thereof. Agent. 3. A collagenase inhibitor, which comprises as an active ingredient a collagenase activity inhibitor which is extracted from Oni strawberry of the Rosaceae family. 4. A leaf part, a stem part, a flower part, a bark of a strawberry,
The collagenase inhibitor according to claim 3, which comprises as an active ingredient a collagenase activity inhibitor obtained by extracting the root part, seed coat, fruit, fruit nucleus or a mixed site thereof with water, a hydrophilic organic solvent or a mixed solvent thereof. . 5. A fibroblast proliferation agent, which comprises a fibroblast proliferation agent extracted from Oni strawberry of the Rosaceae family as an active ingredient. 6. A leaf portion, a stem portion, a flower portion, a bark of a strawberry,
The fiber according to claim 5, which comprises as an active ingredient a fibroblast-proliferating substance obtained by extracting the root part, seed coat, fruit, fruit nucleus or a mixed site thereof with water, a hydrophilic organic solvent or a mixed solvent thereof. A blast-proliferating agent. 7. A skin cosmetic containing the active ingredient according to any one of claims 1 to 6. 8. Ascorbic acid and its derivatives,
The skin cosmetic according to claim 7, wherein one or more skin lightening agents selected from the group consisting of placenta extract, kojic acid, rucinol, arbutin, ellagic acid and chamomile extract are blended. 9. A food and drink for beauty use, which comprises the active ingredient according to any one of claims 1 to 6.