TWI436774B - Skin enhancers and their use - Google Patents

Description

Skin Enhancer and its utilization

The present invention relates to a skin-beautifying agent, an oral composition, and a method for using the same, which is used for improving skin wrinkles, moisturizing, firming, sagging and other skin problems and/or making the skin more The skin-enhancing agent is characterized in that it contains a collagen peptide and a blood flow improving agent as an active ingredient, and the oral composition is formulated with the skin-stimulating agent.

The skin is composed of epidermis, dermis, and subcutaneous tissue. The epidermis is composed of a stratum corneum, a granular layer, a spinous layer and a basal layer, and contains a large number of cells such as keratinocytes and melanocytes, and has a function of preventing harmful substances or pathogens from invading from the outside, and inhibiting evaporation of water. . Unlike the epidermis, the dermis has fewer cells and is mainly composed of extracellular components. The extracellular components are proteins and mucopolysaccharides produced by fibroblasts. The proteins are collagen and elastin. The polysaccharides are hyaluronic acid and chondroitin sulfate, and the dermis forms a matrix structure to produce the following functions: support cells and skin tissues; maintain moisture in the intercellular space; maintain lubricity and softness of the skin; protect skin tissue It is protected from external factors such as ultraviolet rays, dry environment, mechanical irritation and damage, and microbial infection (Non-Patent Document 1).

However, the aforementioned extracellular matrix component may be affected by an increase in age, or may be affected by ultraviolet rays in daily life, but denatured, decomposed, and The amount of extracellular matrix component synthesized is also reduced by aging of fibroblasts. It is known that the skin is caused by various decomposition and synthesis of the aforementioned extracellular matrix, which causes various skin problems such as: dryness; rough skin; reduced elasticity and softness; reduced firmness and gloss; wrinkles, sagging, dullness Increase and so on. Therefore, it is generally considered that in order to improve the skin condition and/or maintain/improve the skin, it is preferred to adopt a method of activating cells of the skin, supplementing and further enhancing the component which is reduced by age or ultraviolet rays. In particular, collagen accounts for about 70% of the dry weight of skin tissue, and is closely related to the viscoelasticity of the skin. In addition, hyaluronic acid is a substance that greatly affects the moisturization of skin tissue, so it is important to maintain/enhance collagen and hyaluronic acid in skin tissue.

In order to enhance the ingredients in skin tissue including collagen and hyaluronic acid, or to inhibit skin aging, various ingredients have been studied, and gelatin and/or collagen decomposition products have been proposed so far (Patent Document 1), N-B. Glucosamine (Patent Document 2), sphingomyelin (Patent Document 3), Genkwanin (Patent Document 4), and Golden Raspberry (Rubus ellipticus) (Patent Document 5).

However, in order to make the physiological effects of these materials appear in the living body, it is sometimes necessary to ingest a large amount, or even if it is taken for a long period of time, an unclear effect may be obtained depending on the individual's condition, or only a certain degree of effect may be obtained. The amount of material capable of exhibiting a practical effect is very small. Therefore, it is required to develop a material or composition having the practical effect of promoting the skin as described above.

On the other hand, the so-called blood flow improver means improving the delivery of blood to The function of the living organizations. The blood system supplies oxygen, nutrients, water, hormones, etc. to the peripheral tissues, and transports immune cells, discharges waste, and regulates body temperature, and plays an important role in maintaining the function of living tissues. It is known that by improving blood flow, it is possible to alleviate the following symptoms: arteriosclerosis, hypertension, decreased immunity, hair loss, fatigue, edema, stiff shoulders, cold hands and feet, paralysis of hands and feet, dark circles, dull skin, etc. .

Substances that improve blood flow have been proposed, for example: Ginkgo biloba extract, safflower extract, placenta extract, capsicum extract, capsaicin, ginseng extract, Swertia japonica extract, fucoidan , vitamin E and its derivatives (tocopherol acetate, etc.), pantothenic acid and its salts (calcium salts, sodium salts, etc.), glycyrrhizic acid (Glycyrrhizin) and glycyrrhetinic acid (Glycyrrhetinic acid) and these salts (sodium salts) , potassium salt, etc.), taheebo extract, arginine and its derivatives (arginine glutamate, etc.), nicotinic acid and its derivatives (methyl ester, etc.), Rosemary extract, ginger extract, gingerol (Shogaol), ginger oil (Gingerol), zingerone, isoflavones, vitamin B ₃ , turmeric extract, grape seeds, leaves, stems, etc. , rutin, rice germ fermentation extract, angelica extract, garlic extract, pepper extract, and the like. However, there is currently no report on the study of the effects of the combination of such blood flow improving substances and the aforementioned skin aging inhibiting ingredients on skin tissue and skin condition.

[Previous Technical Literature] (Patent Literature)

Patent Document 1: Japanese Patent Laid-Open Publication No. 2004-123637

Patent Document 2: Japanese Laid-Open Patent Publication No. 2001-48789

Patent Document 3: Japanese Laid-Open Patent Publication No. 2005-281257

Patent Document 4: Japanese Laid-Open Patent Publication No. 2004-137217

Patent Document 5: Japanese Laid-Open Patent Publication No. 2003-137801

(Non-patent literature)

Non-Patent Document 1: Service Department Dao Hong, "Science of Skin Care", page 6 ~ page 14, (share) Shanghuafang, issued on February 25, 1997

In view of the status quo as described above, the inventors of the present invention have problems in developing a skin-stimulating agent and providing an oral composition and method for improving skin condition such as dry skin, reduced elasticity, and rough skin. And/or promoting the skin, the oral composition is used to promote the skin and the skin is formulated with the skin lightening agent, which is used to improve the skin condition and/or promote the skin.

In order to solve the aforementioned problems, the inventors of the present invention have repeatedly studied the correlation between various materials and skins, and found that the combination of a collagen peptide and a substance having a blood flow improving effect can be unexpectedly produced. Significant effect; in substances with blood flow improving effect, especially extraction from camellia seed extract, thioctic acid, resveratrol and plants containing resveratrol Among the objects At least one of them is more effective in combination with a collagen peptide. In addition, the present invention has been found to be able to effectively utilize the oral composition such as foods, foods, pharmaceuticals, and pharmaceutical products in combination with a combination of a collagen peptide and a substance having a blood flow improving effect.

In other words, the present invention is characterized by a skin-beautifying agent comprising a collagen peptide and a blood flow improving agent as an active ingredient. In the skin-stimulating agent, the collagen peptide is preferably one or more selected from the group consisting of collagen, gelatin, and the like, and the hydrolyzate has a molecular weight (average molecular weight, The following are all about 200 to about 10,000. In addition, the blood flow improving agent is preferably one or more selected from the group consisting of camellia seed extract, lipoic acid, resveratrol, and plant extracts containing resveratrol. .

The camellia seed extract comprises an aqueous component obtained by extracting defatted mash of camellia seed with water and/or a lower alcohol, and the camellia seed extract preferably contains saponin, the soap The genus is preferably one or more selected from the group consisting of Camellia saponin A1, Camellia saponin A2, Camellia saponin B1, Camellia saponin B2, Camellia saponin C1, and Camellia saponin C2. .

Further, the lipoic acid is preferably selected from the group consisting of lipoic acid (including a racemate), a reduced form thereof, salts thereof, such esters, such guanamines, and such cyclodextrin inclusion complexes or lipids. One or two or more selected from the group consisting of the covering materials.

Further, the resveratrol preferably comprises a monomer derived from resveratrol, or a polymer such as ε-glucovin (Viniferin), and the isomers and/or glycosides thereof. One or more selected from the group consisting of, preferably, an extract of a plant of the family Vitis, Polygonaceae or Leguminosae.

Another feature of the present invention is an oral composition which is orally administered with the above-mentioned skin-stimulating agent or the above-mentioned skin-stimulating agent, which is preferably a food or drink. Furthermore, another feature of the present invention is a method, particularly a cosmetic method, for improving skin condition such as dry skin, reduced elasticity, rough skin, and/or promoting skin rejuvenation by oral ingestion of collagen peptide With blood flow improvers.

The skin-stimulating agent of the present invention comprises a collagen peptide and a blood flow improving agent, and has excellent stability such as quality, and has an effect on skin cells, thereby significantly increasing cell proliferation and promoting skin component formation such as collagen and hyaluronic acid. , reply / maintain / enhance the ingredients in the skin tissue. Among the blood flow improving agents, at least one selected from the group consisting of camellia seed extract, lipoic acid, and resveratrol, in combination with the collagen peptide, can further enhance the action. Thereby, it produces an effect of preventing and/or improving skin problems and promoting the skin, which is: dry skin; rough; reduced elasticity and softness; reduced firmness and gloss; wrinkles, sagging, increased dullness, and the like. Such an effect is remarkably exhibited by ingesting the above-mentioned skin-stimulating agent or by orally administering the above-mentioned skin-stimulating agent. Therefore, the skin-stimulating agent can be effectively used in the form of the above-mentioned preparations, or in the form of various preparations in various conventional products, particularly in the fields of foods and drinks, feeds, pharmaceuticals, and pharmaceutical products. use. Further, in the present invention, a cosmetic method for improving skin dryness, reducing elasticity, rough skin, and the like is provided. Skin condition, and / or promote skin, this method is oral intake of collagen peptide and blood flow improver.

[Preferred form of implementing the invention]

The invention is described in detail below. First, the skin-stimulating agent of the present invention is characterized in that it contains a collagen peptide and a blood flow improving agent as an active ingredient.

The collagen peptide used in the skin-stimulating agent of the present invention is a peptide obtained by hydrolyzing collagen or gelatin with an acid, a base or an enzyme, and the gelatin is formed by thermally denaturation of the collagen. The following materials are processed by conventional methods: skin, bone, cartilage, tendon, etc. of cattle, pigs, chickens, turkeys, ostriches, etc.; golden thread, squid, shark, squid, squid, Skin, bone, cartilage or scales of fish such as Nile perch, squid, Sebastes, squid, squid, and squid. Here, in the present invention, the collagen peptide includes a collagen peptide and an extract containing the collagen peptide, and can be used arbitrarily. It is relatively simple to use a commercially available product for the collagen peptide.

In the present invention, it is preferred to use a collagen peptide which hydrolyzes collagen or gelatin, and has a molecular weight of from about 200 to about 10,000, preferably from about 200 to about 5,000, more preferably from about 200 to about 1,000.

Further, as the blood flow improving agent in the skin-stimulating agent of the present invention, for example, an extract of camellia seed, a lipoic acid, a resveratrol, a plant extract containing resveratrol, and a ginkgo biloba extract can be used. , safflower extract, placenta extract, capsicum extract, capsaicin, ginseng extract, drug extract, fucoidan, vitamin E and its derivatives (tocopherol acetate, etc.), pantothenic acid and its salts ( Calcium salt, sodium salt, etc.), glycyrrhizic acid and glycyrrhetinic acid and such salts (sodium salt, potassium salt, etc.), wind chimes bark extract, arginine and its derivatives (arginine glutamate, etc.) ), nicotinic acid and its derivatives (methyl esters, etc.), rosemary extract, ginger extract, gingerol, ginger oil, zingerone, isoflavones, vitamin B ₃ , turmeric extract, grape seeds, leaves Extracts such as stems, stems, etc., rutin, rice germ fermentation extract, angelica extract, garlic extract, pepper extract, etc., are not limited to these examples, and one or two kinds of substances having blood flow improving effects can be used. the above.

In connection with this blood flow improving agent, the present inventors have studied the blood flow improving agent in more detail, and as a result, found that extracts of camellia seed, lipoic acid, and resveratrol or plant extracts containing the resveratrol It is extremely effective, and the blood flow improving agent can exert a more powerful skin-promoting effect by using it in combination with the collagen peptide. In other words, a suitable skin-enhancing agent of the present invention is characterized by comprising the aforementioned collagen peptide and a blood flow improving effect from Camellia seed extract, lipoic acid, resveratrol and resveratrol-containing One or two or more selected from the group consisting of plant extracts are used as active ingredients.

The camellia seed extract of the present invention is described in detail below. The camellia of the present invention refers to Camellia japonica belonging to the Camellia family of Theaceae, and examples thereof include Japanese camellia (C. japonica var. japonica) and snow mountain tea (C. Japonica subsp. Rusticana), C. japonica var. macrocarpa, C. japonica var. hozanensis, C. hongkongensis, C. reticulata, C. saluenensis, southwest The original variant of red camellia (C. pitardii var. pitardii) and narrow-leaved species (C. pitardii var. yunnanica), golden flower tea (C. nisidissima), mountain camellia (the same species as Japanese camellia), and camellia (with Japanese camellia The same species), Yakushima Camellia (the same species as Red Camellia). Such camellia can be used as a wild or cultivated camellia in the Japanese Islands, the Korean Peninsula, and the Shandong Peninsula of China.

In order to produce the camellia seed extract of the present invention, it is preferable to use a degreased product (hereinafter sometimes referred to as defatted mash) as a raw material for supplying the fruit and/or seed of the camellia to a pressing treatment, a supercritical extraction treatment, or the like. The residue is separated by extracting the oil by a conventional method using a hydrophobic organic solvent such as hexane or heptane or a liquefied gas such as liquefied carbon dioxide or liquefied propane. Here, the fruit and/or seed of the camellia may be any of the premature fruit and the mature fruit, and the seed may be used. If the mature fruit or its seed is used, the yield of the degreased substance and/or the active ingredient may be higher. More, and more suitable to use. It is preferred to use seeds. A preferred embodiment is obtained by drying seeds obtained from mature fruits by sunlight or the like for about 1 to 2 weeks.

The active ingredient of the camellia seed extract of the present invention is preferably an aqueous component. The aqueous component can be produced by any method using the above-mentioned defatted mash as a raw material, and it is preferable to carry out extraction treatment using water and/or a lower alcohol. Lower alcohols, because if the carbon number increases, the oily substances in the skim milk are extracted Since the tendency is increased, the carbon number is preferably about 5, and examples thereof include methanol, ethanol, n-propanol, isopropanol, n-butanol, and isobutanol. When a lower alcohol having a large carbon number is used, in order to suppress the extraction of the oil component in the defatted mash, it is preferred to increase the water content. For example, when propanol is used, the water content is set to be about 20 to about 50% by mass, and when butanol is used, the water content is set to be about 40 to about 70% by mass. The extraction solvent is preferably water, methanol and ethanol, and such aqueous alcohols, preferably water or aqueous methanol or aqueous ethanol having a water content of 50% by mass or more, more preferably water.

When the defatted mash is extracted, about 1 to about 30 times the mass of the above extraction solvent is added to 1 part by mass of the defatted mash, and under normal pressure or under a pressure of about 1 to about 5 atm, at a normal temperature to about At 120 ° C, if necessary, the mixture is stirred for about 10 minutes to about 3 hours, and then cooled to room temperature. After filtration, the filtrate is concentrated and dried by a suitable means such as drying under reduced pressure, spray drying or freeze drying. This dried product can be appropriately pulverized. After this, a pale yellow-yellow red solid which is a water-soluble component contained in the camellia seed of the present invention can be obtained. The extraction method can also increase the present invention by performing the same extraction treatment on the extraction residue that has been subjected to the extraction treatment, or performing extraction treatment at about 100 to about 130 ° C under a pressure of about 1 to about 3 atm. The yield of the water-soluble component, and the above-mentioned extract can be further supplied to a conventional means for concentrating and refining the active ingredient, which is a solvent separation; by filling with an ion exchange resin, silicone rubber, activated alumina The column of the adsorbent is separated to separate; the liquid chromatography is used for fractionation and the like. This water-soluble component contains: saponin, tannin, and the like.

The saponin contained in the aforementioned water-soluble component can be exemplified by, for example, 3?-[2-O-?-D-galippyranosyl-3-O-(2-O-?-D-glucopyranose? --α-L-arabinoglucopyranosyl)-β-D-glucosyluronic acid oxylate] lysine 12-ene-16α,22α,28-triol 22-[(Z)- 2-methyl-2-butenoate](3β-[2-O-β-D-galactopyranosyl-3-O-(2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl)-β- D-glucopyranuronosyloxy]olean-12-ene-16α,22α,28-triol 22-[(Z)-2-methyl-2-butenoate]), also known as Camellia saponin A1, 3β-[2-O-β-D - galactosylpyranosyl-3-O-(2-O-β-D-glucopyranosyl-α-L-arabinoglucopyranosyl)-β-D-glucopyranoside ]] 炖果-12-ene-16α,22α,28-triol 22-[(E)-2-methyl-2-butenoate] also known as Camellia Saponin A2, 3β-[2-O -β-D-galactosylpyranosyl-3-O-(2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl)-β-D-glucopyranose Aldouryloxy]-16α,28-dihydroxy-22α-[[(Z)-2-methyl-2-butenyl]oxy] catechin 12-ene-23-aldehyde Camellia saponin B1, 3β-[2-O-β-D-galipurose-3-O-(2-O-β-D-glucopyranosyl-α-L-arabinopyranose )-β-D-glucosyluronic acidoxy]-16α,28-dihydroxy-22α-[[(E)-2-methyl-2-butenyl]oxy] -12-ene-23-aldehyde is also the Camellia saponin B2, 3β-[2-O-β-D-galippyranosyl-3-O-(2-O-β-D-glucopyranose --α-L-arabinoglucopyranosyl)-β-D-gluconofuranosyloxy] kiwi fruit-12-ene-16α,22α,23,28-tetraol 22-[(Z )-2-methyl-2-butenoate], ie, Camellia saponin C1, and 3β-[2-O-β-D-galippyranosyl-3-O-(2-O-β) -D-glucopyranosyl-α-L-arabinoglucopyranosyl)-β-D-glucopyranaloxylate] lysine-12-ene -16α, 22α, 23, 28-tetraol 22-[(E)-2-methyl-2-butenoate], that is, camellia saponin C2 or the like. These saponins are specifically contained in camellia.

Further, the source and type of the lipoic acid of the present invention are not particularly limited as long as it is a natural extract of an organ such as a liver of a cow or a pig, or a chemical composition using, for example, ethylene and an adipate as a starting material. The lipoic acid which can be taken and manufactured by a conventional method can be used. Further, since the lipoic acid has an asymmetric carbon, there are mirror image isomers having different optical properties ((R)-mirrogram isomer and (S)-mirror isomer), but the lipoic acid of the present invention Any of these, or a mixture of any of these, and may also be a racemate (racemic mixture or racemic compound) ((R), (S)-lipoic acid). In terms of the implementation of industrial production grades, it is relatively simple to utilize commercially available racemates that are inexpensive and easily available. When the racemate is used, the tendency of exhibiting the desired effect of the present invention is more strongly exhibited, so that it is preferably used.

The lipoic acid used in the skin-stimulating agent of the present invention can suitably utilize various derivatives in addition to the lipoic acid, and the lipoic acid is preferably derived from lipoic acid, a reduced form thereof, or the like, and the like. One or two or more selected from the group consisting of esters, such guanamines, and the cyclodextrin inclusion complexes.

Specific examples of the reducing body of lipoic acid include dihydrolipoic acid, dihydrolipoic acid, 6,8-dimercaptooctanoic acid, (R), (S)-dihydrolipoic acid, and the like.

Such salts may, for example, be (R)-lipoic acid, (S)-lipoic acid, (R), (S)-lipoic acid, (R)-dihydrolipoic acid, (S)-dihydrolipoic acid. And (R), (S)-dihydrolipoic acid or the like, a potassium salt, a sodium salt, a calcium salt, a magnesium salt or the like.

Such esters may, for example, be (R)-lipoic acid, (S)-lipoic acid, (R), (S)-lipoic acid, (R)-dihydrolipoic acid, (S)-dihydrolipoic acid, (R), (S)-dihydrolipoic acid and the like: with a polyol (ethylene glycol, propylene glycol, butanediol, neopentyl glycol, glycerin, erythritol, polyglycerol, etc. or Part of the ester or complete ester formed by the polymer), or glyceride (monoglyceride, diglyceride, triglyceride); and higher alcohols with a carbon number of 10 to 22 (sterol, lauryl alcohol, nutmeg) Monoesters formed by alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, etc.).

Such guanamines can be exemplified by: (R)-lipoic acid, (S)-lipoic acid, (R), (S)-lipoic acid, (R)-dihydrolipoic acid, (S)-dihydrogen sulfide. Guanidine, octanoic acid, (R), (S)-dihydrolipoic acid, and the like.

Such cyclodextrin inclusion complexes can be exemplified by inclusion of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin or δ-cyclodextrin with the aforementioned lipoic acid or a derivative thereof. Things.

Furthermore, the invention is not limited by the examples.

In the present invention, the lipoic acid also includes a lipid-based coating from the aforementioned lipoic acid, a reduced form thereof, the salts, the esters, the guanamines, and the cyclodextrin. One or two or more kinds of crystals, powders, and/or lipoic acid formed on the outer surface of the group formed by the composition, in which the thermal deterioration (decomposition, polymerization) of the lipoic acid can be suppressed. , discoloration, etc.), moisture absorption or oxidative degeneration, so it is more suitable for practical use.

The lipids covering the surface of the lipoic acid, the powder, and/or the surface of the particles may be any lipids that can be tolerated in the industrial field used in the present invention, and the following lipids may be used alone or in combination: general Edible oils and fats, industrial fats and oils, glycerin fatty acid esters, fatty acids, fatty acid esters, fatty acid guanamines, higher alcohols, waxes, sterols, glycolipids, phospholipids, and the like. In the above, in consideration of the workability of the coating and the physical properties (stability, curability, fluidity, meltability, solubility, and the like) of the covering, it is preferred that the melting point be a lipid of about 30 ° C or higher. A preferred form is a lipid having a melting point of from about 40 ° C to about 70 ° C, and more preferably a lipid having a melting point of from about 40 ° C to about 60 ° C. When the melting point is lower than about 30 ° C, the coated article may not be maintained in a solid state when the coated article is used, and may form agglomerates or may impair fluidity. On the contrary, if the melting point is higher than about 70 ° C, there is a problem that the limonic acid itself is deteriorated by the heat treatment and mechanical energy which are carried out when the accelerator and the composition of the present invention are produced.

Specific examples of such lipids include soybean oil, rapeseed oil, corn oil, sunflower oil, cottonseed oil, wheat germ oil, rice oil, sesame oil, olive oil, safflower oil, palm oil, palm kernel oil, Plant oils such as coconut oil, linseed oil, and peanut oil; animal fats such as tallow, lard, and fish oil; and processed fats and oils obtained by performing one or more of separation, transesterification, decolorization, and deodorization; These hardened oils obtained by partial hydrogenation or complete hydrogenation; saturated fatty acids having a carbon number of 2 to 22 (acetic acid, butyric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, pentadecanoic acid) , palmitic acid, stearic acid, 12-hydroxystearic acid, isostearic acid, arachidic acid, behenic acid, etc.) or unsaturated fatty acids (palmitic acid, oleic acid, oleic acid, linoleic acid, alpha - linolenic acid, gamma-linolenic acid, ricinoleic acid, arachidonic acid, eicosapentaenoic acid (EPA), erucic acid, docosahexaenoic acid (DHA) Etc.); salts of such fatty acids (sodium, potassium, calcium, magnesium, etc.), esters and monohydric alcohols (methanol, ethanol, propanol, butanol, etc.) Partial or complete esters (monoglycerides, diglycerides) formed by monomers or polymers such as ethylene glycol, propylene glycol, butanediol, neopentyl glycol, glycerol, erythritol, etc. Ester, triglyceride); higher alcohols with a carbon number of 10 to 22 (sterol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, etc.); waxes ( Wax derived from plants such as carnauba wax, rice bran wax, Candelilla wax; wax derived from animals such as beeswax, cetyl wax and shellac wax; wax derived from petroleum such as paraffin wax and microcrystalline wax a wax derived from minerals such as montan wax or ceresin; a synthetic wax such as a polyethylene wax, an ester of the aforementioned fatty acid ester and the above higher alcohol; and a sterol (animal cholesterol; vegetable vegetable oil) Sterol, sterol, sitosterol, etc.; ergosterol derived from fungi; such derivatives); phospholipids (source of autologous plant lecithin, phospholipid choline) Phospholipids, ethanolamine, phospholipids, phospholipids, phosphatidic acid, sphingomyelin, etc.; sugar lipids (monoglucose diglyceride, monogalactose diglyceride, diglucosamine monoglyceride, two Galactose monoglyceride, diglucoside diglyceride, digalactose diglyceride, sucrose fatty acid ester, etc.). Furthermore, the invention is not limited by the examples.

In the present invention, any one or a mixture of two or more of the above various types of lipids can be used, and preferred types of the lipids are the above-mentioned edible fats and oils, industrial fats and oils, glycerin fatty acid esters, fatty acid esters, and The waxes are more preferably edible oils and fats and glycerin fatty acid esters, and from the viewpoints of adjusting the melting point of the coated lipids and strengthening the coating film, it is more suitable from the viewpoints of fatty acids and higher alcohols. Sterols, glycolipids or phospholipids One or a combination of two or more selected from the classes.

When the surface of the lipoic acid crystal, the powder, and/or the particle is coated with a lipid, a conventional method can be used. In other words, it can be a method using a ball mill, a flash blender (a powder mixer), a V-type mixer, a high-speed mixer, a high-speed paddle mixer, a heating and melting mixer, and ultrasonic humidification plus a liquid type mixer, a tumbler mixer, a pressurizing extruder, etc., which uniformly mixes the crystals, powders and/or particles of the lipoic acid with the heat-melted lipids, cools them to be solidified, and pulverizes them. a method of coating a lipid which is liquefied by heating, by spraying or dripping on a lipoic acid of the above-mentioned form; and mixing the lipoic acid of the above form with a particulate lipid by high-speed stirring, and mixing the two A method in which a particulate lipid is uniformly adhered to a crystal of a lipoic acid, a powder, and/or a particle to be coated by contact or impact. In the present invention, it is preferred that the crystals, powders and/or particles of the lipoic acid and the particulate lipids having a specific melting point or higher are mixed at a high speed and the two are in contact with each other. Or a method of causing a particulate lipid to be uniformly coated on the entire surface of the above-described form of lipoic acid.

When the coating treatment is carried out, the ratio of the crystals of the lipoic acid, the powder and/or the particles to the lipids, the crystals of the lipoic acid, the shape and size of the powder and the particles, the type and melting point of the lipids, and the coating film. The main factors such as thickness and trait are difficult to be consistently defined. Generally, it is about 0.05 to about 10 parts by mass, and about 0.1 to about 5, with respect to 1 part by mass of the crystals, powders, and/or particles of the lipoic acid. The quality is preferred. If the lipids are less than about 0.05 parts by mass, the coating state is insufficient and it is difficult to develop When the effect is more than about 10 parts by mass, the amount of lipoic acid in the coating material is small. When the coating material is used, the blending ratio or the like may be limited, and the practical value may be impaired.

Further, in the case where the coating material in which the lipoic acid is coated with a lipid is applied to the water-based composition such as a beverage, it is more preferable to further coat the coating with a hydrophilic substance. A coating made of an outer surface. Here, the hydrophilic substance refers to a substance having the ability to form a coating film which is further coated with an outer surface of a coating material coated with a lipid and has affinity with an aqueous substance. Specific examples of the hydrophilic substance include, for example, polysaccharides (three sensilla, guar gum, tamarind gum, psyllium seed gum, etc.), starch and chemical starch, yeast cell wall components, and grapes. Glycan, mannan, shellac, sodium alginate, gelatin, carrageenan, pullulan, carboxymethylcellulose, soy protein, whey protein, zein, and the like. It is preferably one or more selected from the group consisting of polysaccharides, starch, yeast cell wall components, shellac, gelatin, soy protein, zein, and mannan, and more preferably from yeast. One or two or more selected from the group consisting of cell wall components, shellac and gelatin.

When coating with such a hydrophilic substance, a method according to the above-described method of coating a lipid may be employed. In other words, the hydrophilic substance can be dissolved in water, ethanol, or another solvent to form a liquid, and then adhered to the surface of the lipoic acid which has been coated with the lipid in advance and dried to form a hydrophilic substance. A coating of a substance. Such a covering material is formed into a double-coated structure in which a hydrophilic structure is formed When the coated material is used as a food and beverage, a feed, a cosmetic, a pharmaceutical, or the like, the affinity with an aqueous raw material and a component is improved, and it is easy to prepare such a low-water-soluble lipoic acid. A homogeneous composition formed.

In the double coating in which the coating material is coated with a lipoic acid by a lipid and the coating material is further coated with a hydrophilic material as described above, the following components are coated with the following components. The substance is used for coexistence, that is, it is possible to further suppress the heat and/or oxidative denaturation or deterioration of the lipoic acid, and to obtain a sulfur-containing octanoic acid-based coating having excellent stability, and therefore it is more preferable in the present invention. Lipoic acid, which is derived from the extract of garcinia cambogia, the roots of Astilbe thunbergii, the leaves of guava, and the like (from water and/or hydrophilic organic solvents ( One or two or more selected from the group consisting of an extract of a lower-grade monohydric alcohol such as ethanol, acetone, or the like, an extract thereof, a solvent isolate, or a purified product, or a carnitine, and a red Cohos root extract and carnitine are preferred, and carnitine is the best.

The aspect in which the combined raw materials are contained in the above-mentioned sulfur-containing octanoic acid-based coating can be any of the following aspects, or a combination of the same: (i) coating the lipids with the lipoic acid (a) coating the lipid with a crystal, a powder, and/or a particle of a lipoic acid, and mixing the raw material with the concomitant raw material; (iii) a mixture of crystals, powders, and/or particles; a lipid obtained by dispersing or dissolving a part of the above-mentioned combined raw material, coated with a crystal, powder and/or particles of a lipoic acid; (iv) dispersing a solution containing the raw material and the hydrophilic substance Liquid or emulsion, attached The lipid is coated with a coating of a crystal of a lipoic acid, a powder, and/or a particle, and dried to be coated. In the present invention, the aspects (i) and (iv) can easily produce the desired effects of the present invention, and can be easily manufactured, and the handling property of the coated article is also good, but the states (i) and (iii) It is easier to strongly express the desired effect.

In such a form, a mixture of a lipid, a lipid, and a hydrophilic substance coated with a crystal of a lipoic acid, a powder, and/or a particle, and a mixture of the above-mentioned combined raw materials, with respect to the coating 1 The mass of the above-mentioned combined raw materials is preferably from about 0.01 to about 10 parts by mass, preferably from about 0.1 to about 1 part by mass. When it is less than about 0.01 part by mass, it is not confirmed that the desired effect is improved by mixing the raw materials, and if it is more than 10 parts by mass, the content of lipoic acid in the coating is lowered, and further, the coating is used. The content of lipoic acid in the composition is reduced so as to limit the amount of lipoic acid in the various formulations containing the lipoic acid-containing composition, and the desired effect of the lipoic acid itself cannot be expected in the stage of the product.

The source and type of the resveratrol of the present invention are not particularly limited, and can be taken/manufactured using a conventional organic chemical method or a microorganism or a yeast, and it is preferably from a grape family, a family of plants, or a legume family. Plant extracts, stems, leaves, vines, sprouts, seeds, flowers, fruits and other parts are extracted.

The plant which is preferably a source of the resveratrol of the present invention is a plant of the genus Vitis, and the variety thereof is not particularly limited, and examples thereof include: Airen, Aligot, and Valdiguie. , Viognier, Welschriesling, Ortega, Cabernet Sauvignon, Cabernet Franc), Gamay, Carignan, Garganega, Carmenere, Xinomavro, Gruner Veltliner, Gewu Gewurztraminer, Kerner, Koshu, Colombard, Cinsaut, Sagrantino, Sangiovese, Saint Laurent (St. Laurent), Chasselas, Chardonnay, Chenin Blanc, Scheurebe, Semillon, Sauvignon Blanc, Tannat ), Zweigelt, Tempranillo, Traminer, Dolcetto, Dornfelder, Pinot meunier, Pusa Poulsard), Furmint, Portugieser, Muscat, Malvasia, Malbec, Muscadelle, Muller -Thurgau), Mourvedre, Melon, Morio-Muskat, Muscadine, Vitis amurensis, Aki Queen, Vidal Blanc, Kyoho, Seto Giants, Seyval Blanc, Delaware, Niagara, New Mies Neo Muscat, Baco Noir, Baco Blanc, Pione, Muscat Bailey, Fujisawa, Roman Ruby, Kaifei Road, Jiazhou Sanjiu, etc. These may be extracted from the wild parts of Japan, Chile, Italy, France, etc., and should be extracted from the various parts of the above-exemplified varieties. The parts are stems, vines, sprouts or flowers. good.

The resveratrol of the present invention can be produced by any method, and can be as follows; using the stem, vine, sprout or flower itself of the grape exemplified above, or using the dried, finely cut, After the pulverization treatment, the extract is immersed in a solvent for a certain period of time or in contact with an extraction solvent heated under reflux to obtain an extract, and then the solvent is removed from the extract to obtain an extract; Performing a purified product obtained by column chromatography or solvent separation using an adsorbent such as tannin extract, magnesium niobate, ion exchange resin, activated alumina, cellulose, or activated carbon; and by freeze drying, spray drying And other methods to make these powders obtained by powdering. When it is used in foods, from the viewpoint of convenience and production cost, it is preferred to use a water or a hydrophilic organic solvent to dry the portion of the plant and then pulverize it to obtain a powder, a fine slice of the dried product, or The powder is extracted to prepare an extract. Further, when it is used in pharmaceutical applications, it is preferably the above-mentioned extract, extract or purified product of high purity.

The hydrophilic organic solvent may, for example, be a lower monohydric alcohol such as methanol, ethanol, propanol or isopropanol; a polyhydric alcohol such as propylene glycol, 1,3-butanediol or glycerin; acetone; methyl ethyl ketone; ether; petroleum ether. Ethyl acetate; and such hydrates and mixtures. In order to efficiently obtain an extract for producing the desired effect of the present invention, ethanol, acetone, ethyl acetate and the like are preferably used as the solvent for extraction. The moisture content of the hydrate is, for example, about 1 to about 99 mass% when ethanol is used, preferably about 50 mass% or less, and when acetone is used, it is about 1 to about 50 mass%, and about 10 to about 30% by mass is preferred, when ethyl acetate is used, it is about From 80 to about 99% by mass, preferably from about 85 to about 95% by mass. If it exceeds these ranges, the desired effect of the present invention may be reduced, or the yield of the extract may be lowered.

The resveratrol of the present invention is trans-resveratrol (a monomer of resveratrol), or ε-glucoside (dimer), or Miyabenol C (trimer). A polymer such as a stilbene compound such as an isomer and/or a glycoside thereof is targeted. Further, when the extract obtained from the above plant is used, the active ingredient mainly composed of the above stilbene-based compound may include: quercetin, ellagitannin, ellagic acid ), minerals (such as: potassium, calcium, phosphorus, magnesium), vitamins.

In the skin-stimulating agent of the present invention, the blood flow improving agent used in combination with the collagen peptide is about 0.01 to about 50% by mass, preferably about 0.1 to about 20% by mass, more preferably about 0.1 to about 20% by mass. It is preferably from about 0.5 to about 10% by mass. If it is less than about 0.01% by mass, the effect obtained by the combination may be small, and conversely, even if it is used in excess of about 50% by mass, the desired effect cannot be expected to be more excellent. Further, the blood flow improving agent can be arbitrarily used by using one of the aforementioned conventional substances or extracts, or arbitrarily using a plurality of the above-mentioned conventional substances or extracts, preferably from camellia seed extract, lipoic acid, and resveratrol. And one or two or more selected from the group consisting of plant extracts containing resveratrol, and it is more preferable to contain all of them. When two or more kinds of camellia seed extract, lipoic acid, resveratrol, and plant extract containing resveratrol are used in combination, the ratio (mass basis) is roughly: Camellia seed extract/lipoic acid Class is 20/80~60/40, with 30/70~40/60 Preferably, the camellia seed extract/resveratrol is 99/1~30/70, preferably 80/20~50/50, and the lipoic acid/resveratrol is 99/1~30/70. Preferably, the Camellia Seed Extract/Lipoic Acid/Resveratrol contains the following ratio: the ratio of each blood flow improving agent is about 1 of the total skin promoting agent. The mass% or more is preferably about 10% by mass or more. Further, when a plant extract containing resveratrol is used, it may be set in consideration of the content of resveratrol in the extract.

The skin-beautifying agent contains a combination of a collagen peptide and a blood flow improving agent as an active ingredient, and can be used as it is, that is, it is formed into a powder form only composed of the aforementioned active ingredients. The solid shape, the syrup, or the liquid form is used in foods, medicines, pharmaceutical products, and feeds, and the blood flow improving agent is especially derived from camellia seed extract, lipoic acid, and white. One or two or more selected from the group consisting of resveratrol and a plant extract containing resveratrol.

In addition, the skin-stimulating agent of the present invention can be suitably used in combination with a conventional additive which can be used in the above-mentioned use in which the skin-stimulating agent can be used, and can be used as an oral composition. . Here, the conventional additive may be an additive which is generally used for oral ingestion, for example, an excipient, a binder, a disintegrant, a lubricant, a wetting agent, a fluidizing agent, a preservative, and an interfacial activity. Additives such as agents, stabilizers, diluents, solubilizers, tonicity adjusters, bactericides, preservatives, flavoring agents, flavoring agents, colorants, perfumes, and the like. Further, it is not limited to the components described in the above-mentioned prior documents, and a conventional component having a skin-beautifying action and/or a blood flow improving effect and a material containing the component can be used in combination. Skin promotion of the present invention The agent can also be used as part of the blending materials of various products such as foods and drinks, pharmaceuticals, pharmaceutical products, feeds, and other industrial fields. In particular, it is preferable to manufacture a product for beauty or the like.

When the skin-stimulating agent of the present invention is used in combination with a conventional additive to prepare an oral composition, an orally-administered preparation can be prepared in the form of a powder, a granule, a tablet, a capsule, or a liquid. And other forms.

The content of the above-mentioned active ingredient in such a composition for oral use is difficult to be uniformly defined depending on the type and content of the raw materials to be used, and is approximately 0.1 to 100% by mass, preferably about 10 to about 100. quality%. If the content is less than about 0.1% by mass, the desired effect of the present invention cannot be confirmed. The skin-stimulating agent of the present invention is utilized by a method of oral ingestion or oral administration. In this case, the preferred intake or administration amount of the oral composition of the present invention is based on the base of the active ingredient contained in the skin-stimulating agent, and is a human adult (body weight: 50 kg) per Approximately 100 mg to about 100,000 mg on the 1st, preferably from about 500 mg to about 10,000 mg, more preferably from about 1,000 mg to about 5,000 mg.

The skin-stimulating agent of the present invention can be utilized as part of a raw material for a conventional product such as a food or beverage, a pharmaceutical product, a pharmaceutical product, or a feed. Examples of practical articles are described below, but the invention is not limited by the examples.

Specific examples of the food and drink include, for example, various general processed foods such as vegetable juice, fruit juice drink, refreshing drink, and tea; cake premix powder, bread, cake, biscuit, chocolate, candy, gummy candy, chewing gum, etc. Dim Sum; miso, soy sauce, sauce, mayonnaise, barbecue sauce and cold noodles Seasonings such as sauce; instant noodles such as instant noodles, udon noodles, soba noodles, and pasta; processed meat products such as ham and sausage; powdered milk such as milk, yogurt, whipped cream, cream, bread sauce and cheese, Solid or liquid dairy products; fragrant pine, burger, cola cake, side dish, jam, soup, jelly, pudding, salad dressing, vegetal cream, margarine, etc., in addition to powdered, granules The following foods in the form of pills, pills, lozenges, soft capsules, hard capsules, pastes or liquids: nutritional supplements; foods for specific health care; functional foods; health foods; thick liquid foods and swallows Food for treatment of foods for obstacles, etc.

In the production of such foods and drinks, one of the conventional materials may be replaced by the conventional method using the skin-stimulating agent of the present invention and a known material, or by replacing the part of the conventional material with the skin-stimulating agent of the present invention. It is preferably used as a nutritional supplement food or a health food in the following manner. For example, the skin lightening agent of the present invention is mixed with edible materials such as powders or extracts as needed, and processed into powders, granules, pills. a shape of a tablet or the like; or a form of a general processed food processed by the conventional method into the above-described example; or coated with a mixed powder or liquid with a coating agent such as gelatin, sodium alginate or carboxymethylcellulose Formed into a capsule; or processed into a form of a beverage (drinks) containing: dextrose, glucose, dextrin, lactose, starch or a processed product thereof, excipients such as cellulose powder, vitamins, ore Oils and fats of substances, animals, plants and fish and shellfish (including proteins derived from automatic plant and yeast, hydrolysates thereof, etc.), saccharides, pigments, perfumes, antioxidants, surfactants, other edible additives, various nutrient functional ingredients . In particular, it is preferably in the form of a tablet, a capsule, and a drink. Furthermore, these diets The content and intake amount of the skin-stimulating agent of the present invention contained in the product are substantially the same as those of the above-mentioned oral composition.

By using the pharmaceutical preparation of the skin-stimulating agent of the present invention and the external product of the medical department, it is possible to appropriately add a pharmaceutically acceptable excipient and addition to the above-mentioned skin-stimulating agent without departing from the gist of the present invention. The preparation is processed into a tablet, a capsule, a granule, a powder, a liquid, and the like by a conventional method. This medicine and the external products of the Ministry of Medicine are administered orally, and are suitable for prevention or treatment of dryness, reduced elasticity, and rough skin. In addition, the content and the intake amount of the skin-stimulating agent of the present invention contained in the pharmaceutical products and the external products of the medical department are based on the above-mentioned oral composition.

Further, when the skin-stimulating agent of the present invention is applied to a pet food or a feed for livestock, it can be formulated in various kinds of feeds and drinking waters, or with conventional materials, as in the case of the above-described foods and drinks. The additives are processed together into a preparation form such as a tablet form, a granule form, or a capsule form. The content and intake amount of the skin-stimulating agent of the present invention in these feeds are substantially the same as those of the above-mentioned oral composition.

[Examples]

Next, the present invention will be described in detail by way of examples, but the present invention is not limited by the examples. In each of the examples, %, parts, and ratios represent the quality basis unless otherwise specified.

[Production Example 1] (Collagen peptide (1))

5 L of water was added to 1 kg of the skin remaining after removing the body and bone of the squid, and then heated to 85 ° C under normal pressure and stirred for 1 hour, and gelatin was extracted. After cooling the gelatin solution to 50 ° C, add proteolytic enzymes. The enzyme was allowed to react for 2 hours. Then, the enzyme was deactivated and filtered to separate the filtrate. The filtrate was concentrated under reduced pressure, and freeze-dried and pulverized to obtain 192 g of collagen peptide (Sample 1). After the collagen peptide was subjected to HPLC (high performance liquid chromatography) analysis by a conventional method, the average molecular weight was about 1,000.

[Production Example 2] (collagen peptide (2))

The scales of the koi fish were treated with 0.1 N hydrochloric acid, washed with a large amount of water, and dried by sunlight. After adding 8 L of water to dry scales of 1 kg, it was heated to 85 ° C under normal pressure and stirred for 1 hour, and gelatin was extracted. After the gelatin solution was cooled to 50 ° C, a proteolytic enzyme was added to carry out an enzyme reaction for 1 hour. Then, the enzyme was deactivated and filtered to separate the filtrate. The filtrate was concentrated under reduced pressure, and freeze-dried and pulverized to obtain 711 g of collagen peptide (Sample 2). After HPLC analysis of this collagen peptide by a conventional method, the average molecular weight was about 5,000.

[Production Example 3] (Camellia Seed Extract (1))

The dried seeds of Japanese camellia produced by Izu Oshima are roughly pulverized and cooked, and then pressed, and the pressed oil is separated to obtain a press mash (degreased product). After adding 3 L of water to the press crucible 1 kg, it was heated to 85 ° C under normal pressure and stirred for 1 hour, then cooled to room temperature, and filtered to separate the filtrate. 1 L of water was added to the filtration residue again, and the mixture was heated, stirred, and cooled in the same manner, filtered, and the filtrate was collected. The two filtrates are mixed, concentrated under reduced pressure, and freeze-dried and pulverized to obtain a water-soluble component. Powdered Camellia Seed Extract (Sample 3) 170 g. The extract was subjected to HPLC analysis by a conventional method, and the result contained 7.5% of saponin B2, 5.8% of saponin C2, and 2.4% of flavonol (Kaempferol).

[Production Example 4] (Camellia Seed Extract (2))

2 L of aqueous ethanol (water content: 35%) was added to the degreased product obtained in the same manner as in Production Example 3, and the mixture was heated under reflux at 80 ° C for 1 hour, cooled to room temperature, and filtered to separate the filtrate. Further, 2 L of aqueous ethanol (water content: 35%) was added to the filtration residue, and heating was carried out in the same manner. After cooling, the filtrate was filtered and collected. The two filtrates were mixed, concentrated under reduced pressure, and freeze-dried and pulverized to obtain 12.1 g of a powder (sample 4) containing a water-soluble component. This powder was subjected to HPLC analysis in the same manner as in Production Example 3, and as a result, 8.3% of Camellia Saponin B2, 5.9% of Camellia C2, and 2.9% of flavonol, which is also a flavonol.

[Production Example 5] (Lipid coating of lipoic acid)

200 g of rapeseed hardened oil (melting point: 67 ° C, flake), which was heated and melted, was added to a crystalline powder of lipoic acid (trade name: ALIPURE (registered trademark), manufactured by Alz Chem, Germany) 330 g of the racemate, thoroughly mixed to make it uniformly dispersed, and then solidified by cooling at room temperature. Then, the solidified product was pulverized in a high-speed mixer, and sieved using a 100 mesh (Tyler mesh, the same hereinafter) to obtain a lipoic acid lipid coating having a particle diameter of 150 μm or less ( Sample 5).

[Production Example 6] (cyclodextrin inclusion compound of lipoic acid)

Lipoic acid of crystalline powder (made by AlzChem, Germany, trade name: 100 g of ALIPURE (registered trademark), racemate) was dissolved in 500 mL of 50% ethanol, and then added with α-cyclodextrin (manufactured by Wacker Chemie, Germany, trade name: CAVAMAX (registered trademark) (R) W6), and appropriately After stirring, it was concentrated and spray-dried to obtain a lipoic acid cyclodextrin inclusion compound (Sample 6).

[Production Example 7] (Resveratrol Extract)

500 g of the dried sunlight of the stem of the grape (Cabernet) was reflux-extracted in 2 L of a 70% ethanol solution, and the filtrate was separated by filtration. Further, 1 L of 70% ethanol was added to the filtered residue, and after reflux extraction, the filtrate was separated by filtration. The two filtrates were mixed, concentrated under reduced pressure, and cyclodextrin was added thereto, followed by spray drying to obtain 24 g of resveratrol extract powder (Sample 7). The powder was subjected to HPLC analysis by a conventional method, and the result contained trans-resveratrol 6.2% and ε-glucoside 6.0%.

[Test Example 1] (blood flow improvement effect)

A total of 40 subjects (24-65 years old, 20 males, 20 females) who had agreed to participate in the tests described below were grouped into 5 groups, and blood flow measurement tests were performed by a double-blind test. First, subjects were allowed to enter a constant temperature and humidity room controlled at a temperature of 24 ± 2 ° C and a humidity of 50 ± 10%, and they were allowed to wait for 10 minutes. Then, using a laser Doppler blood flow meter (Peried, PeriScan PIM II), the blood flow of the back of the hand before the test sample was taken was measured. Then, the control group (placebo group) was ingested with a hard capsule filled with cyclodextrin and 100 mL of water which was colored so that the subject could not be distinguished by color, and the other group was infused with the same color as described above. The hard capsules and water of each test sample were 100 mL, and the blood flow of the back of the hand was measured again in the same manner as described above after 30 minutes and 60 minutes. Furthermore, the test sample is set to: Camellia seed extract (Sample 3, Sample 4), commercially available lipoic acid, lipoic acid lipid coating (Sample 5), resveratrol extract (Sample 7), commercially available Ginkgo biloba extract (BHN) )), and ginseng extract (Maruzen Pharmaceutical Co., Ltd.).

The results are shown in Table 1. In Table 1, the numerical value is a relative value (n = 5, ANOVA analysis) when the value before the placebo and the test substance is taken as 100, and is expressed by the mean value ± standard deviation. From the data in Table 1, it was not possible to confirm that the blood flow of the back of the hand and the scalp of the subjects taking placebo had a significant change, but when ingesting samples 3 and 4 (camera seed extract), lipoic acid and sample 5 (lipoic acid) In the case of the lipid coating) and the sample 7 (resveratrol extract), it was confirmed that the blood flow promoting action was the same as that of the conventional Ginkgo biloba extract and the ginseng extract, and after 30 minutes of ingestion and 60 At two points after the minute, the blood flow value of the back of the hand increased significantly.

[Test Example 2] (Promoting effect of skin fibroblast proliferation)

The effects on the proliferation of dermal fibroblasts were investigated by the following methods. In other words, use a petri dish ( 10 cm), D-MEM medium (Dulbecco's Modified Eagle's Medium, Dulbecco's Modified Eagle's Medium) supplemented with 10% fetal bovine serum (manufactured by Daiichi Co., Ltd.) (Sigma-made, low glucose) In the normal human adult skin fibroblasts (KURABO (NH), NHDF (NB), hereinafter referred to as cells only) 2 × 10 ⁵ , and cultured for 4 days until it becomes subconfluent (density of about 80) %)until. Then, the medium was removed, and the cells were washed twice with 5 mL of PBS (phosphate buffered saline), and then washed with 5 mL of 0.02% EDTA (Ethylenediaminetetraacetic acid) solution. Thereafter, the cells were recovered using 5 mL of a 0.25% trypsin solution (manufactured by NACALAI TESQUE), and after centrifugation (4 ° C, 1,000 rpm, 5 minutes), the supernatant was removed and washed twice with PBS. And get the cells. This cell was repeatedly cultured under the aforementioned conditions, and subculture was carried out.

Using a 96-well cell culture plate (0.32 cm ² , manufactured by AGC TECHNO GLASS), a low serum medium for human skin fibroblast proliferation (KURABO (manufactured by KURABO), in skin fibroblast basal medium (106S) 500 mL Among the mediums supplemented with 10 mL of low serum proliferation additive (LSGS), the above-mentioned subcultured cells were seeded at 1 × 10 ⁴ cells/well and cultured for 24 hours. Then, the medium was removed, and culture was continued for 48 hours in the low serum medium for human skin fibroblast proliferation in which the respective samples were added so that the final concentration became 5, 10 or 20 μg/mL. Then, 25 μL of a MTT solution (PBS containing thiazolyl blue tetrazolium bromide (a reagent manufactured by Sigma)) at a concentration of 5 mg/mL was added, and culture was carried out for 1 hour. After removing the medium completely by decantation, add a (formazan) solution (containing 25% (v/v) 0.45 M acetate buffer (pH 4.5), 25% (v/v) N, N-dimethylformamide, 10% (w/v) positive ten Sodium dialkyl sulfate, pH 4.5) 100 μL and stirred. After allowing to stand at room temperature for 1 night, the absorbance at 590 nm was measured, and the degree of proliferation of the cells was evaluated. Further, in the above method, the D-MEM medium and the human serum fibroblast proliferation low serum medium are set to add penicillin (final concentration 100 IU/mL) and streptomycin (final concentration 0.1 mg/mL). The cell culture was carried out in a CO ₂ incubator (37 ° C, 5% CO ₂ enhanced gas phase). Furthermore, the test samples were set to: the aforementioned collagen peptide (Sample 1, Sample 2), Camellia seed extract (Sample 3, Sample 4), commercially available lipoic acid, lipoic acid lipid coating (Sample 5) , lipoic acid cyclodextrin inclusion compound (Sample 6), resveratrol extract (Sample 7), commercially available Ginkgo biloba extract (BHN (manufactured by BHN), ginseng extract (Maruzen Pharmaceutical Co., Ltd.) ), and sample 1 or sample 2 is used in combination with each sample.

The results are shown in Table 2, Table 3 and Table 4. In Tables 2, 3, and 4, the numerical values are expressed as relative values when the value of the comparative test (when no sample is added) is set to 100. In Table 2, in the medium, Sample 1 was added to make the final concentration 50 μg/mL, Sample 2 was added to make the final concentration 100 μg/mL, and other samples were added to make the final concentration 5 and 10 μg/ mL. In Tables 3 and 4, samples 1 and 2 were set to 50 μg/mL, and other samples were set to 5 μg/mL each. In the medium.

From the data of Table 2, although it was weak, it was confirmed that each sample promoted the proliferation of skin fibroblasts in each added concentration.

Further, from the data of Table 3, when the samples 3 to 7 and the lipoic acid were used in combination with the sample 1, it was apparent that the action of the fibroblasts was multiplied. Further, by using Sample 3, Sample 7, and Lipoic Acid in combination with Sample 1, the proliferation effect can be enhanced. However, in the group of Ginkgo biloba extract and ginseng extract, the effect of enhancing the proliferation of fibroblasts could not be confirmed.

From the data in Table 4, it was confirmed that the effect of enhancing the proliferation of fibroblasts was confirmed, but it was confirmed that the proliferative effect was lower than the data (value) of Table 3.

Further, the sample peptide 1 and the sample 2 were replaced with a collagen peptide having an average molecular weight of about 300, and the test was carried out in the same manner. As a result, the fibroblast proliferation-promoting effect obtained by the combined use was compared with the tendency of the data of Table 3. Equivalent or higher (data omitted).

As apparent from the above, the present invention significantly promotes the proliferation of human skin fibroblasts by combining a collagen peptide with a blood flow improving agent, particularly in combination with camellia seed extract, lipoic acid, and resveratrol. effect.

Furthermore, although the test data is omitted, it can be confirmed in the test example that when Sample 1 or Sample 2 is used in combination with the above three blood flow improving ingredients, human skin fibrils are used as compared with the case where they are used alone. The ability of cells to produce collagen and hyaluronic acid is significantly improved.

[Test Example 3] (Human skin test)

60 adult females (35-55 years old, mean age: 48.6 years) who have agreed to participate in the tests described below with low skin elasticity and low moisture content Grouped, 5 in each group, please take each sample for 6 weeks. Before and after ingesting the sample, the skin elasticity was measured using a skin viscoelasticity measuring device (Courage+Khazaka, Germany, product name: CUTOMETER MPA580(R)), and a moisture measuring device (Corneometer (R) CM825) was used for a certain part of the face. The relative value of moisture was measured. Further, the test was carried out by the above-mentioned sample 1, sample 3, sample 7, lipoic acid, a combination thereof, and the same ginkgo biloba extract as described above. The intake was set to 5 g for sample 1 and 200 mg for the other samples. When using the combination with sample 1, the sample was set to 5 g for sample 1 and 200 mg for other samples. .

The results are shown in Table 5. Regarding the skin elasticity and moisture content before and after ingestion of the sample, when each sample other than the Ginkgo biloba extract was ingested, a slight improvement effect was observed after the ingestion, but there was not much difference before the ingestion. However, when other samples were separately combined with the sample 1, the skin elasticity and the moisture content were significantly improved, and it is apparent that the present invention combines the collagen peptide with the blood flow improving agent, particularly the collagen peptide and the camellia seed. The extract, the lipoic acid, and the resveratrol are used in combination, and have a significant effect of promoting the skin-beautifying effect.

[Trial Example 1] (soft capsule)

Samples 1 and 3 (mixing ratio: 10/1), sample 1 and sample 7 (mixing ratio: 10/1), sample 1 and lipoic acid (mixing ratio: 10/1), sample 1 and sample 3, respectively. And 200 parts of any one of the combination of the sample 7 and the lipoic acid (mixing ratio: 10/1/1/1), 40 parts of beeswax and 50 parts of evening primrose oil (manufactured by Efamol Co., Ltd.) were added and heated and mixed to homogenize. After the solution, it was supplied to a capsule filling machine, and a gelatin-coated soft capsule preparation of 250 mg per content was tried by a conventional method. This capsule preparation can be utilized as a nutritional supplement food, a pharmaceutical product, or an animal feed which can be orally ingested.

[Trial Example 2] (hard capsule)

Samples 1 and 3 (mixing ratio: 10/1), sample 1 and sample 4, and sample 6 (mixing ratio: 10/3/1), sample 1 and sample 4, and sample 7 (mixing ratio: 10/) 1/1), sample 1 and sample 4, and sample 5 and sample 7 (mixing ratio: 10/2/1/1) are supplied to a capsule filling machine and tested by a conventional method. A 200 mg gelatin coated hard capsule preparation. This capsule preparation can be utilized as a nutritional supplement food, a pharmaceutical product, or an animal feed which can be orally ingested.

[Trial Example 3] (beverage)

In 100 mL of commercially available nutritional drinks, sample 1 and sample 3 (mixing ratio: 10/1), sample 1 and sample 7 (mixing ratio: 10/1), sample 1 and lipoic acid (mixing ratio: 10) were added. /1) A combination of 1,000 mg each, and mixed thoroughly, and tried to make a drink. Even if the beverage was stored in the refrigerator for 6 months, it was impossible to confirm that the appearance and flavor were abnormal and uncomfortable. The beverage can be utilized as a beverage or a drink for improving the skin condition such as dryness, reduced elasticity, rough skin, and/or promoting skin.

[Industrial availability]

The skin-stimulating agent of the present invention contains, as an active ingredient, a combination of one or more selected from the group consisting of a collagen peptide and a specific one of the three kinds of blood flow improving agents, and the beauty of the present invention is ingested by oral administration. The skin promoter or the skin-stimulating agent of the present invention can be administered orally, and has the effects of improving dryness of the skin, reducing elasticity, rough skin, and/or promoting skin-beautifying, so that it can be used in foods, medicines, and medicines. Effective use in the fields of feed and feed.

Claims (8)

A skin-beautifying agent characterized by comprising only a collagen peptide and a blood flow improving agent as an active ingredient; wherein the blood flow improving agent is a group consisting of camellia seed extract and lipoic acid One or two selected ones; the aforementioned lipoic acid is coated with lipoic acid (racemate), a cyclodextrin inclusion compound of the lipoic acid, and outer surfaces of the crystals, powders or particles. The lipids are edible fats having a melting point of about 40 ° C to 70 ° C. The skin-enhancing agent according to claim 1, wherein the blood flow improving agent is further used in combination with a resveratrol and/or a plant extract containing the resveratrol; and the resveratrol contains t a composition of resveratrol and/or ε-glucosamine; a plant extract containing the aforementioned resveratrol, which is obtained by using a stem, a vine or a sprout of a plant belonging to the genus Vitis. The skin-stimulating agent according to claim 1 or 2, wherein the collagen peptide is a hydrolyzate of collagen or a hydrolyzate of gelatin, and has an average molecular weight of 200 to 10,000. The skin-stimulating agent according to claim 1, wherein the camellia seed extract is an aqueous component obtained by extracting defatted mash of camellia seed with water and/or a lower alcohol. The skin-stimulating agent according to claim 1 or 4, wherein the camellia seed extract contains saponin, and the saponin comprises sorbitan A1 and camellia saponin A2 represented by the following chemical names. Selected from the group consisting of Camellia Saponin B1, Camellia Saponin B2, Camellia Saponin C1 and Camellia Saponin C2 One or more of them; wherein the aforementioned Camellia saponin A1 is 3β-[2-O-β-D-galippyranosyl-3-O-(2-O-β-D-graspomycin) Cyclosyl-α-L-arabinoglucopyranosyl)-β-D-glucopyranaloxyl] lysine 12-ene-16α, 22α, 28-triol 22-[(Z )-2-methyl-2-butenoate]; the aforementioned Camellia saponin A2 is 3β-[2-O-β-D-galippyranosyl-3-O-(2-O-β- D-glucopyranosyl-α-L-arabinoglucopyranosyl)-β-D-glucosyluronic acid oxylate] lysine 12-ene-16α,22α,28-triol 22 -[(E)-2-methyl-2-butenoate]; the aforementioned Camellia saponin B1 is 3β-[2-O-β-D-galippyranosyl-3-O-(2- O-β-D-glucopyranosyl-α-L-arabinoglucopyranosyl)-β-D-glucosyluronic acidoxy]-16α,28-dihydroxy-22α-[[( Z)-2-methyl-2-butenyl]oxy] catechin 12-ene-23-aldehyde; the aforementioned Camellia saponin B2 is 3β-[2-O-β-D-galiper Cyclosyl-3-0-(2-O-β-D-glucopyranosyl-α-L-arabinoglucopyranosyl)-β-D-glucopyranosideoxy]-16α , 28-dihydroxy-22α-[[(E)-2-methyl-2-butenyl]oxy] ligated fruit-12-ene-23-aldehyde; the aforementioned Camellia saponin C1 is 3β-[ 2-O-β-D- galactosylpyranosyl-3-O-(2-O-β-D-glucopyranosyl-α-L-arabinoglucopyranosyl)-β-D-glucopyranoside Qiguoguo-12-ene-16α,22α,23,28-tetraol 22-[(Z)-2-methyl-2-butenoate]; the aforementioned camellia saponin C2 is 3β-[2- O-β-D-galactosylpyranosyl-3-O-(2-O-β-D-glucopyranosyl-α-L-arabinoglucopyranosyl)-β-D-glucopyran Uronic acid acylate] lysine 12-ene-16α, 22α, 23, 28-tetraol 22-[(E)-2-methyl-2-butenoate]. A composition for oral administration, which comprises the skin-stimulating agent according to any one of claims 1 to 5, wherein the blood flow improving agent is two or more; however, the blood flow improving agent does not comprise a combination of lipoic acid And resveratrol or a combination of lipoic acid and a plant extract containing the aforementioned resveratrol. The oral composition according to claim 6, wherein the oral composition is a food or drink. A cosmetic method for improving skin condition such as dry skin, reduced elasticity, rough skin, and/or promoting skin beauty, the cosmetic method characterized by: oral ingestion as described in any one of claims 1 to 5 The blood flow improving agent in the skin-stimulating agent is two or more skin-stimulating agents; or the oral composition as described in claim 6.