WO2012147842A1 - Beautiful-skin-promoting agent and use thereof - Google Patents

Abstract

The present invention addresses the problem of providing a beautiful-skin-promoting agent for improving skin conditions such as dry skin, loss of elasticity, and chapped skin and/or for promoting beautiful skin; an oral composition for promoting beautiful skin containing the beautiful skin-promoting agent; and a beautifying method for improving skin condition and/or promoting beautiful skin. Provided is a beautiful skin-promoting agent that contains as an active ingredient one or a combination of two or more types selected from the group consisting of collagen peptides and blood flow-improving agents; especially camellia seed extract, thioctic acids, resveratrols, and plant extracts containing resveratrols, as well as an oral composition containing the beautiful-skin-promoting agent, and a method for oral intake of the beautiful-skin-promoting agent or the composition.

Description

Beautiful skin promoter and its use

The present invention comprises a collagen peptide and a blood flow improving agent as active ingredients, for improving skin troubles such as skin wrinkles, moisture, firmness, sagging and / or more beautiful skin The present invention relates to a beautifying skin-promoting agent, an oral composition containing the beautifying skin-promoting agent, and methods for using these.

The skin is composed of epidermis, dermis and subcutaneous tissue. The epidermis is composed of the stratum corneum, granule layer, spiny layer and basal layer, and contains many cells such as keratinocytes and melanocytes, and plays a role in preventing invasion of harmful substances and pathogens from the outside, and suppressing the transpiration of moisture. Yes. In the dermis, unlike the epidermis, there are few cells, and it is occupied by extracellular components such as proteins produced by fibroblasts such as collagen and elastin, and mucopolysaccharides such as hyaluronic acid and chondroitin sulfate. , Support of cells and skin tissues, water retention in cell gaps, maintenance of skin lubricity and flexibility, role of protecting skin tissues from external factors such as ultraviolet rays, dry environment, mechanical irritation and damage, microbial infection, etc. (Non-Patent Document 1).

However, the extracellular matrix components are denatured and decomposed under the influence of aging and daily ultraviolet rays, and the amount of synthesis is also reduced by the deterioration of fibroblasts. Degradation of the extracellular matrix and a decrease in the amount of synthesis may cause various skin troubles such as dryness, rough skin, reduced elasticity and flexibility, decreased firmness and gloss, wrinkles, sagging and dullness. Are known. Therefore, in order to improve the skin condition and / or maintain / promote beautiful skin, it is desirable to activate skin cells to supplement and further enhance components that have decreased due to aging or ultraviolet rays. In particular, collagen accounts for about 70% of the dry weight of the skin tissue and is deeply involved in the viscoelasticity of the skin. Moreover, since hyaluronic acid is a substance that has a great influence on the moisture retention of skin tissue, it is important to maintain and enhance collagen and hyaluronic acid in the skin tissue.

Various components have been studied in order to enhance components in skin tissues such as collagen and hyaluronic acid, and to suppress skin aging. Gelatin and / or collagen degradation products (Patent Document 1) ), N-acetylglucosamine (patent document 2), sphingomyelin (patent document 3), genkwanin (patent document 4), oni strawberry (patent document 5) and the like have been proposed.

However, in order to express the physiological action of these materials in vivo, it is necessary to ingest a large amount, and even if ingested over a long period of time, the effect is not clear depending on the individual, or only a certain effect In some cases, it was not possible to obtain it, and there were few things that could be practically effective. Therefore, there has been a demand for the development of effective materials and compositions that promote the above-mentioned beautiful skin.

By the way, the blood flow improving agent improves the function of transporting blood to each tissue of a living body. Blood plays a very important role in maintaining the functions of living tissues by supplying oxygen, nutrients, water, hormones, and the like to peripheral tissues, transporting immune cells, discharging waste products, and regulating body temperature. Improve blood flow to relieve symptoms such as arteriosclerosis, hypertension, decreased immunity, alopecia, fatigue, swelling, stiff shoulders, coldness, numbness in the limbs, dark circles under the eyes and skin dullness Are known.

Examples of substances that improve blood flow include ginkgo biloba extract, safflower extract, placenta extract, capsicum extract, capsaicin, carrot extract, assembly extract, fucoidan, vitamin E and its derivatives (such as tocopherol acetate), pantothenic acid and Its salts (calcium salt, sodium salt, etc.), glycyrrhizic acid and glycyrrhetinic acid and their salts (sodium salt, potassium salt, etc.), tahibo extract, arginine and its derivatives (arginine glutamate, etc.), nicotinic acid and its derivatives (methyl) Esters, etc.), rosemary extract, ginger extract, gingerol, gingerol, gingeron, isoflavone, vitamin B ₃ , turmeric extract, grape seed, leaf, stem, etc. extract, rutin, rice germ ferment extract, toki extract , Garlic extract, Down show extract, and the like have been proposed. However, there are no reports on the effects of the combination of these blood flow improving substances and the skin aging inhibitory components on the skin tissue and skin condition.

Japanese Patent Laid-Open No. 2004-123637 JP 2001-48789 A JP 2005-281257 A JP 2004-137217 A JP 2003-137801 A

In view of the present situation, the present inventors have developed a skin enhancement agent that improves skin conditions such as skin dryness, reduced elasticity, and rough skin, and / or promotes beautiful skin, and is formulated with the skin enhancement agent. An object of the present invention is to provide an oral composition for promoting skin and a method for improving skin condition and / or promoting beautiful skin.

In order to solve the above problems, the present inventors have conducted extensive studies on the relationship between various kinds of materials and beautiful skin, and as a result, the combination of a collagen peptide and one having an effect of improving blood flow is surprisingly remarkable. Collagen peptide comprising at least one selected from plant extracts containing camellia seed extract, thioctic acids, resveratrols and resveratrols It was found that it is extremely effective to use in combination. Furthermore, the present inventors have found that this can be effectively used for oral compositions such as foods and drinks, feeds, pharmaceuticals, and quasi drugs, and have completed the present invention.

That is, the feature of the present invention resides in a skin beautification promoter comprising a collagen peptide and a blood flow improving agent as active ingredients. In this skin beautification promoter, the collagen peptide is preferably one or more selected from the group consisting of collagen, gelatin, and hydrolysates thereof, and the hydrolyzate has a molecular weight (average molecular weight, below). The same) is preferably from about 200 to about 10,000. The blood flow improving agent may be one or more selected from the group consisting of camellia seed extract, thioctic acid, resveratrol and plant extract containing resveratrol, among others. desirable.

The camellia seed extract contains an aqueous component obtained by extracting defatted camellia seeds with water and / or lower alcohol, and preferably contains saponins, and the saponins are particularly Camellia saponins ( More preferably, it is one or more selected from Camellia saponin) A1, Camellia saponin A2, Camellia saponin B1, Camellia saponin B2, Camellia saponin C1, and Camellia saponin C2.

The thioctic acids are selected from the group consisting of thioctic acid (including racemate), its reduced form, their salts, their esters, their amides, and their cyclodextrin inclusions or lipid coatings. It is desirable to be a seed or two or more.

Furthermore, resveratrol is a resveratrol monomer, or a polymer such as ε-viniferin and one or more selected from the group consisting of isomers and / or glycosides thereof. It is desirable to include the extract, and the embodiment is more preferably an extract of a plant belonging to the vine family, the laceaceae or the legume family.

Another feature of the present invention is an oral composition for orally ingesting or administering the skin beautifying agent, and the oral composition is preferably a food or drink. Still another feature resides in a method for ingesting a collagen peptide and a blood flow improving agent orally, improving skin conditions such as dry skin, reduced elasticity, rough skin, and / or promoting beautiful skin, especially a cosmetic method.

The skin-beautifying agent of the present invention contains a collagen peptide and a blood flow improving agent, is excellent in stability such as quality, acts on skin cells to remarkably increase its proliferation, and skin components such as collagen and hyaluronic acid It promotes the production of and restores, maintains, and enhances components in skin tissue. Among the blood flow improving agents, this action is enhanced by using at least one selected from camellia seed extract, thioctic acids, and resveratrol with a collagen peptide. This prevents and / or ameliorates skin problems such as skin dryness, roughness, loss of elasticity and flexibility, reduction in elasticity and gloss, wrinkles, sagging and dullness, and also promotes beautiful skin. Play. Such an effect is remarkably exhibited by ingesting or administering the skin beautifying agent orally. For this reason, the said skin beautification agent can be effectively used with the form of the said agent, or the form mix | blended with the conventional various products especially in field | areas, such as food-drinks, feed, a pharmaceutical, and a quasi-drug. In addition, the present invention provides a cosmetic method for orally ingesting a collagen peptide and a blood flow improving agent to improve skin conditions such as dry skin, reduced elasticity, and rough skin and / or promote beautiful skin.

The present invention will be described in detail below. First, the skin beautification promoter of the present invention is characterized by containing a collagen peptide and a blood flow improving agent as active ingredients.

Collagen peptides used in the skin beautification promoter of the present invention include cattle, pigs, chickens, turkeys, ostriches and other animal skins, bones, cartilage, tendons, etc., lobsters, salmon, sharks, cod, tilapia, Nile perch, carp, rockfish, It is a peptide obtained by hydrolyzing collagen, obtained by treatment of fish skin such as tuna, catfish, eel, etc., bone, cartilage, scales, etc. by conventional methods, or gelatin obtained by heat denaturation of the collagen with acid, alkali or enzyme. is there. Here, the collagen peptide in the present invention includes a collagen peptide and an extract containing the same, and these can be arbitrarily used. It is easy to use a commercially available collagen peptide.
In the present invention, it is desirable to use a collagen peptide obtained by hydrolyzing collagen or gelatin, and has a molecular weight of about 200 to about 10,000, more preferably about 200 to about 5,000, still more preferably about 200 to It is about 1,000.

Further, the blood flow improving agent related to the skin beautifying agent of the present invention includes, for example, camellia seed extract, thioctic acid, resveratrol, plant extract containing resveratrol, ginkgo biloba extract, safflower extract Products, placenta extract, capsicum extract, capsaicin, carrot extract, assembly extract, fucoidan, vitamin E and its derivatives (such as tocopherol acetate), pantothenic acid and its salts (calcium salt, sodium salt, etc.), glycyrrhizic acid and glycyrrhetic acid Salts thereof (sodium salt, potassium salt, etc.), tahibo extract, arginine and derivatives thereof (arginine glutamate, etc.), nicotinic acid and derivatives thereof (methyl ester, etc.), rosemary extract, ginger extract, gingerol, gingerol, Zingeron, isoflavone, bitami B _3, turmeric extract, extract of such seeds, leaves and stems of grape, rutin, rice germ fermented extract, Japanese angelica root extract, garlic extract, may be used, pepper extract, and the like, are not limited to these examples One or two or more of those having an effect of improving blood flow can be used.

In this connection, the present inventors have examined in further detail a blood flow improving agent that can exhibit a more powerful skin-promoting effect when used in combination with a collagen peptide. As a result, an extract of camellia seeds, It has been found that thioctic acids and resveratrols or plant extracts containing them are extremely effective. That is, the desirable skin beautification promoter of the present invention is selected from the group consisting of the aforementioned collagen peptide and a plant extract containing camellia seed extract having a blood flow improving effect, thioctic acids, resveratrols and resveratrols. It contains one or two or more selected as active ingredients.

The camellia seed extract according to the present invention will be described in detail below. The camellia refers to camellia japonica belonging to the camellia section of the genus Theaceae, Camellia, and examples thereof include C. japonica var. Japonica, (C. japonica var. Macrocarpa), C. japonica subsp. Hozanensis, C. hongkongenesis, C. reticulata, C. isluen pi. pterardii var. pitardii) and Yunnan species (C. pita) dii Var.Yunnanica), KimuHanacha (C.Nitidissima), Yamatsubaki (Camellia japonica and the like), sasanqua (Camellia japonica and the like), may be mentioned Yakushimatsubaki (apples Camellia same kind), and the like. What is necessary is just to utilize suitably these camellia which are growing naturally in the Japanese archipelago, the Korean peninsula, the Shandong peninsula of China, etc.

In order to produce the camellia seed extract according to the present invention, the aforementioned camellia fruits and / or seeds are squeezed, a hydrophobic organic solvent such as hexane or heptane, or a liquefied gas such as liquefied carbon dioxide or liquefied propane is used. It is desirable to use a defatted material (hereinafter sometimes referred to as defatted soot), which is a residue obtained by extracting and separating oil by a conventional method, for example, a supercritical extraction treatment. Here, the camellia fruits and / or seeds may be either early-ripening fruits or mature fruits, and these seeds may be used, but when mature fruits or seeds thereof are used, the yield of defatted products and / or active ingredients is high. It is desirable. More preferably seeds are used. In a preferred embodiment, seeds obtained from mature fruits are dried for about 1 to 2 weeks in the sun.

The active component of the camellia seed extract according to the present invention is desirably an aqueous component. The aqueous component can be produced by any method using the defatted soy sauce as a raw material, but it is preferable to perform extraction using water and / or a lower alcohol. The lower alcohol has a tendency to extract oily substances in the defatted soot as the carbon number increases. Therefore, those having a carbon number of up to about 5 are desirable. Methanol, ethanol, normal propanol, isopropanol, normal butanol, Examples include butanol. When using a lower alcohol having a large carbon number, it is preferable to increase the water content in order to suppress the extraction of oily components in the defatted soot. For example, the water content in the case of propanol is about 20 to about 50% by mass, and the water content in the case of butanol is about 40 to about 70% by mass. Desirable extraction solvents are water, methanol and ethanol, and water-containing alcohols thereof, more preferably water or water-containing methanol or water-containing ethanol having a water content of 50% by mass or more, and more preferably water.

In order to extract the defatted soot, the extraction solvent is added about 1 to about 30 times by mass with respect to 1 part by weight of the defatted soot, and at about normal pressure or about 1 to about 5 atm. After stirring and mixing for 10 minutes to about 3 hours as necessary, the mixture is cooled to room temperature and filtered, and the filtrate is concentrated and dried by an appropriate means such as drying under reduced pressure, spray drying or freeze drying. This dried product may be appropriately pulverized. In this way, a light yellow to yellow-red solid that is a water-soluble component contained in camellia seeds according to the present invention can be obtained. In the extraction method, the extraction residue once extracted is similarly subjected to repeated extraction treatment, or is performed at about 100 to about 130 ° C. under a pressure of about 1 to about 3 atmospheres, thereby yielding the yield of the water-soluble component according to the present invention. In addition, the extract can be further subjected to known means such as solvent fractionation, fractionation with a column packed with an adsorbent such as ion exchange resin, silica gel, activated alumina, and fractionation by liquid chromatography. It can also be used to concentrate and purify the active ingredient. This water-soluble component includes saponin, tannin and the like.

As the saponin contained in the water-soluble component, 3β- [2-O-β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) ) -Β-D-glucopyranuronosyloxy] oleana-12-ene-16α, 22α, 28-triol 22-[(Z) -2-methyl-2-butenoate] Camellia saponin A1, 3β- [2-O-β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) -β-D-glucopyranurono Camellia saponin A2, 3 which is (siloxy) oleana-12-ene-16α, 22α, 28-triol 22-[(E) -2-methyl-2-butenoate] β- [2-O-β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) -β-D-glucopyranurono Syloxy) -16α, 28-dihydroxy-22α-[[(Z) -2-methyl-2-butenoyl] oxy] oleana-12-en-23-al, Camellia saponin B1, 3β-[[[ 2-O-β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) -β-D-glucopyranuronosyl) oxy ] -16α, 28-dihydroxy-22α-[[((E) -2-methyl-2-butenoyl] oxy] oleana-12-en-23-al, Camellia saponin B2, 3β -[2-O-β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) -β-D-glucopyranuronosyl Oxy] oleana-12-ene-16α, 22α, 23,28-tetraol 22-[(Z) -2-methyl-2-butenoate] Camellia saponin C1, and 3β- [2-O -Β-D-galactopyranosyl-3-O- (2-O-β-D-glucopyranosyl-α-L-arabinopyranosyl) -β-D-glucopyranuronosyloxy] oleana-12 Examples include Camellia saponin C2, which is -ene-16α, 22α, 23,28-tetraol 22-[(E) -2-methyl-2-butenoate]. These saponins are specifically contained in camellia.

The origin and type of thioctic acids according to the present invention are not particularly limited, and natural product extracts of organs such as livers of cattle and pigs, for example, chemicals starting from ethylene and adipic acid esters are used. It may be collected and produced by a known method such as a synthetic product. Since thioctic acid has an asymmetric carbon, there are enantiomers ((R) -enantiomer and (S) -enantiomer) having different optical properties. However, thioctic acid according to the present invention can be any one of these. It may be a mixture in an arbitrary ratio, or may be a racemate (racemic mixture or racemate) ((R), (S) -thioctic acid). In the implementation at the industrial production level, it is convenient to use a commercially available racemate that is inexpensive and easily available. Use of a racemate is desirable because it tends to exert the desired effect of the present invention more strongly.

The thioctic acids used in the skin beautifying agent of the present invention can appropriately utilize various derivatives in addition to the above thioctic acid, such as thioctic acid, its reduced form, their salts, their esters, their amides, and It is desirable that they be one or more selected from the group consisting of those cyclodextrin inclusions.
Specific examples of the reduced form of thioctic acid include dihydrothioctic acid, dihydrolipoic acid, 6,8-dimercapto-octanoic acid, (R), (S) -dihydrothioctic acid and the like.
Salts include (R) -thioctic acid, (S) -thioctic acid, (R), (S) -thioctic acid, (R) -dihydrothioctic acid, (S) -dihydrothioctic acid, (R), ( Examples thereof include potassium salts such as S) -dihydrothioctic acid, sodium salts, calcium salts, and magnesium salts.
Esters include (R) -thioctic acid, (S) -thioctic acid, (R), (S) -thioctic acid, (R) -dihydrothioctic acid, (S) -dihydrothioctic acid, (R), ( S) -dihydrothioctic acid and the like and partial alcohols or complete esters or glycerides (monoglycerides, monomers such as ethylene glycol, propylene glycol, butanediol, neopentyl glycol, glycerol, erythritol, polyglycerol, etc.) And monoesters with higher alcohols having 10 to 22 carbon atoms (decanol, lauryl alcohol, myristyl alcohol, cetanol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, etc.). .
Amides include (R) -thioctic acid, (S) -thioctic acid, (R), (S) -thioctic acid, (R) -dihydrothioctic acid, (S) -dihydrothioctic acid, (R), ( Examples include amides such as S) -dihydrothioctic acid.
Examples of the inclusion product of cyclodextrin include an inclusion product of α-, β-, γ-, or δ-cyclodextrin and the thioctic acid or its derivative.
In addition, this invention is not limited by these illustrations.

In the present invention, as the thioctic acids, one or more crystals selected from the group consisting of the above thioctic acid, its reduced form, their salts, their esters, their amides, and their cyclodextrin inclusion products. In addition, powders and / or particles whose outer surface is coated with lipids are included, and this embodiment is practical for suppressing thermal alteration (decomposition, polymerization, discoloration, etc.), moisture absorption or oxidative modification of thioctic acids. In particular, it is more desirable.

The lipids that coat the outer surface of the thioctic acid crystals, powder, and / or particles may be acceptable as long as they are acceptable in the industrial field in which the present invention is used, such as general edible oils or industrial fats and oils, Fatty acid glycerides, fatty acids, fatty acid esters, fatty acid amides, higher alcohols, waxes, sterols, glycolipids, phospholipids and the like can be used alone or in combination. Of these, lipids having a melting point of about 30 ° C. or higher are preferable in consideration of coating workability and physical properties of the coating (stability, solidification, fluidity, meltability, solubility, etc.). More preferred forms are lipids having a melting point of about 40 ° C. to about 70 ° C., and still more preferred forms are lipids having a melting point of about 40 ° C. to about 60 ° C. When the melting point is less than about 30 ° C., the coating may not be able to maintain a solid state during use, and may form a lump or impair flowability. On the other hand, when the temperature exceeds about 70 ° C., the thioctic acids themselves may be deteriorated due to the influence of heat treatment or mechanical energy in producing the inhibitor or composition according to the present invention.

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, coconut oil, linseed oil , Vegetable oils such as peanut oil, animal fats such as beef tallow, lard, fish oil, processed oils and fats that have been subjected to one or more of such treatments as fractionation, transesterification, decolorization, deodorization, etc., partially or completely Various hydrogenated hydrogenated oils, saturated fatty acids having 2 to 22 carbon atoms (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 (palmitoleic acid, oleic acid, elaidic acid, linoleic acid, α-linole Acid, γ-linolenic acid, ricinoleic acid, arachidonic acid, icosapentaenoic acid (EPA), erucic acid, docosahexaenoic acid (DHA), etc., salts of these arbitrary fatty acids (sodium salt, potassium salt, calcium salt, magnesium salt, etc.) ) Part with esters with monohydric alcohols (methanol, ethanol, propanol, butanol, etc.), polyhydric alcohols (monomers or polymers such as ethylene glycol, propylene glycol, butanediol, neopentyl glycol, glycerin, erythritol, etc.) Complete esters or glycerides (monoglyceride, diglyceride, triglyceride), higher alcohols having 10 to 22 carbon atoms (decanol, lauryl alcohol, myristyl alcohol, cetanol, stearyl alcohol) Isostearyl alcohol, behenyl alcohol, etc.), waxes (carnauba wax, rice wax (rice bran wax), plant-derived waxes such as candelilla wax, beeswax, whale wax, shellac wax and other animal-derived waxes, paraffin wax, microcrystalline wax, etc. Oil-derived wax, wax derived from minerals such as montan wax, ozokerite, polyethylene wax, synthetic waxes such as esters of the above fatty acids and higher alcohols, sterols (animal cholesterol, plant campesterol, stigma) Sterol, sitosterol, etc., fungus-derived ergosterol, derivatives thereof, phospholipids (animal and plant-derived lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylino) Thor, phosphatidylserine, phosphatidic acid, sphingomyelin, etc.), glycolipids (monoglucosyl diglyceride, monogalactosyl diglyceride, diglucosyl monoglyceride, digalactosyl monoglyceride, monoglucosyl diglyceride, digalactosyl diglyceride, sucrose fatty acid ester, etc.) Can do. In addition, this invention is not limited at all by these illustrations.

In the present invention, any one or a mixture of two or more of the above-mentioned various lipids can be used. Preferred types of lipids include the above-mentioned edible oils or industrial fats, fatty acid glycerides, fatty acid esters and Waxes, more preferably edible fats and oils and fatty acid glycerides, and these and one or more selected from fatty acids, higher alcohols, sterols, glycolipids or phospholipids The combination is a more desirable embodiment from the viewpoint of adjusting the melting point of the coated lipid, reinforcing the coating film, and the like.

In order to coat the outer surface of the thioctic acid crystals, powder and / or particles with lipids, a known method can be used. That is, ball mill, flash blender (powder granule mixer), V-type mixer, high-speed mixer, high-speed paddle mixer, heat-melt mixer, ultrasonic super-humidified liquid-type mixer, tumbler mixer, pressure extruder, etc. The thioctic acid crystals, powder and / or particles and the heated and melted lipids are uniformly mixed, cooled and solidified, and then pulverized. A method of coating by spraying or dripping the lipids which have been formed, and stirring and mixing the thioctic acids of the above-mentioned form and particulate lipids at high speed, and bringing them into contact or colliding with each other, thereby producing crystals, powders and / or thioctic acids. Alternatively, a method in which particulate lipids are uniformly attached to the entire surface of the particle and coated is possible. In the present invention, among these, thioctic acid crystals, powders and / or particles and particulate lipids having a specific melting point or higher are mixed with high-speed stirring, and both are brought into contact with or collided with each other to obtain the thioctic acid of the above form. A method of uniformly coating particulate lipids on the entire surface of acids is desirable.

In the above-described coating treatment, the ratio of thioctic acid crystals, powders and / or particles to lipids, thioctic acid crystals, powder and particle shapes and sizes, lipid types and melting points, coating film thickness and Although it is difficult to define uniformly depending on factors such as properties, about 0.05 to about 10 parts by mass, preferably about 0.1 parts by weight of lipids are generally added to 1 part by mass of crystals, powders and / or particles of thioctic acids. About 5 parts by mass. If the lipid is less than about 0.05 parts by mass, the coating state is not sufficient and the desired effect is hardly exhibited. Conversely, if it exceeds about 10 parts by mass, the thioctic acid content in the coating is low, In the scene where it is used, the blending rate and the like are limited, and the practical value may be impaired.

The above-described coating of thioctic acids with lipids is more preferably an embodiment in which the outer surface is further coated with a hydrophilic substance regardless of whether or not this is applied to an aqueous composition such as a beverage. More desirable. Here, the hydrophilic substance means a substance that further coats the outer surface of the coating with lipids and has a coating film-forming ability having an affinity with an aqueous substance. Specific examples include polysaccharides (xanthan gum, guar gum, Tamarind seed gum, psyllium seed gum), starch and modified starch, yeast cell wall components, glucan, mannan, shellac, sodium alginate, gelatin, carrageenan, pullulan, carboxymethylcellulose, soy protein, whey protein, zein, etc. Can do. More preferably, it is one or more selected from the group consisting of polysaccharides, starch, yeast cell wall components, shellac, gelatin, soybean protein, zein and mannan, and more preferably from yeast cell wall components, shellac and gelatin. 1 type or 2 types or more chosen from the group which consists of.

In order to coat with such a hydrophilic substance, a method according to the above-described lipid coating method may be employed. That is, the hydrophilic substance is appropriately dissolved in water, ethanol, or other solvent to form a liquid, and this is attached to the outer surface of thioctic acid previously coated with lipids and dried to coat the hydrophilic substance. A film can be formed. Such a coating becomes a double-coated structure having a hydrophilic substance as the outermost layer, and when this is used for foods, drinks, feeds, cosmetics, pharmaceuticals, etc., the affinity with aqueous raw materials and ingredients increases, It becomes easy to prepare a homogeneous composition with thioctic acids having low solubility.

In the above-described coating of thioctic acids with lipids and the double coating in which the coating is further coated with a hydrophilic substance, these include Garcinia camphor peel, red pepper rhizome, guava leaf and extracts thereof (water And / or one or two selected from the group consisting of an extract with a hydrophilic organic solvent (e.g., a lower monohydric alcohol such as ethanol, acetone, its fraction, a solvent fraction or a purified product), and carnitine. As described above, thioctic acids having excellent stability that can further suppress thermal and / or oxidative denaturation and deterioration of thioctic acids by coexisting coexistence with red pepper rhizome extract and carnitine, most preferably carnitine. Such an embodiment of thioctic acid is more desirable in the present invention because a containing coating is obtained.

In the embodiment in which these combination raw materials are contained in the above-mentioned thioctic acid-containing coating, (i) the combination raw materials are mixed in a coating in which lipids are coated on thioctic acid crystals, powder and / or particles, (ii) (Iii) Disperse a part of the combination raw material in the thioctic acid crystals, powder and / or particles, and coat the lipid with a mixture of the thioctic acid crystals, powder and / or particles and the combination raw material. (Iv) a solution, dispersion or emulsion containing the thioctic acid crystals, powders and / or particles coated with lipids, and the combined raw material and the hydrophilic substance. It is possible to apply and dry and coat, and a combination of these embodiments may be used. In the present invention, the aspects (i) and (iv) exhibit the desired effects of the present invention, the production is simple, and the handling workability of the coating is good, but the aspects (i) and (iii) are desirable. It is easy to express the effect of.

In such an embodiment, the mixing ratio of the coating material obtained by coating the crystals, powders and / or particles of thioctic acid with lipids or lipids and a hydrophilic substance, and the combination raw material, is used in combination with 1 part by mass of the coating material. The raw material is about 0.01 to about 10 parts by weight, more preferably about 0.1 to about 1 part by weight. When the amount is less than about 0.01 parts by mass, the desired effect cannot be improved by mixing the combined raw materials. When the amount exceeds about 10 parts by mass, the thiocte in the coating and further in the composition using the same. The acid content is lowered, and as a result, the thioctic acid content in various products containing the thioctic acid-containing composition is limited, and the desired effect of thioctic acid itself cannot be expected in the product stage.

The origin and type of resveratrol according to the present invention is not particularly limited, and may be a well-known organic chemical method, or one collected / manufactured using a microorganism, yeast, etc. It is desirable that it is obtained by extraction from parts such as pericarp, stem, leaf, vine, shoot, seed, flower, fruit, etc.

More desirable plants as the origin of resveratrols according to the present invention are grapevine genus plants, and the varieties thereof are not particularly limited. For example, Eileen, Arrigote, Valdigier, Viognier, Versch Riesling, Ortega, Cabernet Sauvignon, Cabernet Franc, Turtle, Carignan, Garganega, Carmener, Kusinomavroro, Grüner Feltrina, Gewurztraminer, Kerner, Koshu, Colombar, Sanso, Sagrantino, Sangiovese, Saint-Laurent, Chasselas, Chardonnay, Chenin Blanc, Schoillebe, Semillon, Sauvignon Blanc, Tana, Zweigert, Tempranillo, Traminer, Dolchette, Dornfelder, Pinot Meunier, Pull , Full mint, portugueseer, muscat, malvazia, malbec, muska del, muller thurgau, mur vedor, mullon, morio muscat, muscadine, strawberry amur grapes, aki queen, vidal blanc, kyoho, seto giants, saval Brand, Delaware, Niagara, Neo Muscat, Baco Noir, Baco Blanc, Pione, Muscat Bailey, Minori Fuji, Ruby Roman, Kai Road, Koshu Sansha etc. What is necessary is just to utilize what is naturally grown or cultivated in Japan, Chile, Italy, France, etc., and extracts from each part of the cultivar illustrated above, more preferably stem, vine, shoot or flower. Is good.

The resveratrols according to the present invention can be produced by an arbitrary method, but the above-exemplified grape stems, vines, shoots or flowers themselves, or those obtained by drying, chopping and pulverizing them. These are immersed in a solvent for a certain period of time, or are brought into contact with an extraction solvent that is heated to reflux to obtain an extract, an extract obtained by removing the solvent from the extract, silica gel, magnesium silicate in the extract , Ion-exchange resin, activated alumina, cellulose, purified products that have been subjected to purification treatment such as column chromatography using an adsorbent such as activated carbon and solvent fractionation, and those that have been pulverized by methods such as freeze-drying and spray-drying But you can. When used for food applications, it is convenient and manufacturing cost to use a powder obtained by drying the plant part and pulverizing it appropriately, or using an extract obtained by extracting fine fragments or powder of the dried product with water or a hydrophilic organic solvent. From the point of view is desirable. Moreover, when using for a pharmaceutical use, the said extract, an extract, or a highly purified product is desirable.

As hydrophilic organic solvents, lower monohydric alcohols such as methanol, ethanol, propanol and isopropanol, polyhydric alcohols such as propylene glycol, 1,3-butanediol and glycerin, acetone, methyl ethyl ketone, ether, petroleum ether, ethyl acetate and These hydrates and mixtures can be exemplified. In order to efficiently obtain an extract for producing the desired effect of the present invention, it is preferable to use ethanol, acetone, ethyl acetate and a hydrated product thereof as an extraction solvent. The water content of the hydrated product is, for example, about 1 to about 99% by mass in the case of ethanol, more preferably about 50% by mass or less, and about 1 to about 50% by mass in the case of acetone, more preferably about 10%. In the case of ethyl acetate, about 80 to about 99% by weight, more preferably about 85 to about 95% by weight. Outside these ranges, the desired effect of the present invention is reduced or the yield of the extract is reduced.

Resveratrols according to the present invention include t-resveratrol (resveratrol monomer), polymers such as ε-viniferin (dimer), Miyabenol C (trimer), and These isomers and / or stilbene compounds such as glycosides are targeted. The extract obtained from the plant may contain quercetin, ellagitannin, ellagic acid, minerals (for example, potassium, calcium, phosphorus, magnesium) and vitamins as the main active ingredients. .

In the skin beautification promoter of the present invention, the content of 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 of the total of the agent. More desirably, the amount is about 0.5 to about 10% by mass. When the amount is less than about 0.01% by mass, the effect of the combined use is small. On the other hand, when the amount exceeds about 50% by mass, a further desired effect cannot be expected. In addition, the blood flow improving agent can be arbitrarily used alone or in combination with the above-mentioned known substances and extracts, but desirable ones include camellia seed extract, thioctic acids, resveratrols and resveratrols. It is 1 type, or 2 or more types selected from the plant extract to do, and what is still more desirable is what contains all these. Camellia seed extract, thioctic acid, resveratrol, and the ratio (mass basis) when using two or more kinds of plant extracts containing resveratrol in general are camellia seed extract / thioctic acid 20/80 to 30/70, more preferably 60/40 to 40/60, and camellia seed extract / resveratrol is 99/1 to 30/70, more preferably 80/20 to 50/50 The thioctic acid / resveratrol is 99/1 to 30/70, more preferably 80/20 to 50/50, and the camellia seed extract / thioctic acid / resveratrol is used for each blood. It is desirable that the ratio of the flow improver is about 1% by mass or more, more preferably about 10% by mass or more, based on the whole skin beautifying agent. In the case of a plant extract containing resveratrol, the content may be set in consideration of the content of resveratrol in the extract.

The aforementioned skin beautification promoter is one or two selected from the group consisting of collagen peptides and blood flow improving agents, especially camellia seed extract, thioctic acids, resveratrols and plant extracts containing resveratrols The combined use with the above as an active ingredient, as it is, that is, in the form of powder, solid, paste or liquid consisting only of the active ingredient, this is food and drink, pharmaceuticals, quasi drugs, It can be used for applications such as feed.

The skin-beautifying agent of the present invention can also be used as an oral composition by appropriately combining known additives for the above-mentioned uses for which it can be used and containing them in a conventional manner. Here, known additives may be those usually used for ingestion, for example, excipients, binders, disintegrants, lubricants, wetting agents, fluidizing agents, preservatives, surfactants. Additives such as stabilizers, diluents, solubilizers, tonicity agents, bactericides, preservatives, flavoring agents, flavoring agents, coloring agents, and fragrances can be used. Furthermore, it is not limited to the thing as described in the said prior art document, You may use together the known component which has the beautiful skin effect and / or blood flow improvement effect, and its containing material. The skin beautifying agent of the present invention can also be used as a part of a blended raw material of various products in food and drink, pharmaceuticals, quasi drugs, feeds, and other industrial fields. In particular, it is preferably a product for beauty and the like.

When the skin beautifying agent of the present invention is used in combination with known additives to form an oral composition, it can be made into oral preparations such as powders, granules, tablets, capsules, and liquids. It is.
The content of the active ingredient in such an oral composition is difficult to define uniformly depending on the type and content of the raw materials used together, but is generally about 0.1 to 100% by mass, more preferably about 10 to about 100% by mass. %. When the content is less than about 0.1% by mass, the desired effect of the present invention is not recognized. The skin beautification promoter of the present invention is used in a method of taking or administering it orally. In this case, the preferred intake or dosage of the oral composition of the present invention is about 100 mg to about 100,000 mg per day for a human adult (body weight 50 kg) based on the active ingredient contained in the agent. It is desirably about 500 mg to about 10,000 mg, more desirably about 1,000 mg to about 5,000 mg.

The skin-beautifying agent of the present invention can be used as a part of a blended raw material of known products such as foods and drinks, pharmaceuticals, quasi drugs, and feeds. Examples of practical products are described below, but the present invention is not limited to these exemplifications.

Specific examples of foods and beverages include beverages such as vegetable juice, fruit juice drinks, soft drinks and teas; cake premix products, breads, cakes, cookies, chocolates, candy, gummies, gums and other sweets; miso, soy sauce, sauces , Mayonnaise, grilled meat sauce, noodle soup, etc .; noodles such as instant noodles, udon, soba noodles, spaghetti, etc .; processed meat and fish products such as ham and sausage; Dairy products in the form of solid, liquid or liquid; sprinkles, hamburger, croquettes, boiled potatoes, jam, soup, jelly, pudding, dressing, vegetable cream, margarine, etc. Pharmaceutical, tablet, soft capsule, hard capsule, paste or liquid food supplement, food for specified health use, machine Sex food, mention may be made of health food products, the concentrated liquid diet and dysphagia for food diet and the like.

In order to produce these foods and beverages, the skin beautification promoter of the present invention and known raw materials may be used, or a part of the known raw materials may be replaced with the skin beautification promoter of the present invention and manufactured by conventional methods. For example, the skin-beautifying agent of the present invention may be added to excipients such as glucose, glucose, dextrin, lactose, starch or processed products thereof, cellulose powder, vitamins, minerals, fats and oils of animals, plants, and seafood as needed. White (including proteins derived from animals and plants and yeasts, hydrolysates thereof), carbohydrates, pigments, fragrances, antioxidants, surfactants, other edible additives, powders and extracts containing various nutritional functional ingredients, etc. Mixed with edible ingredients and processed into powders, granules, pellets, tablets, etc., processed into the form of general processed foods of the above examples by conventional methods, mixed powders and liquids with gelatin, sodium alginate, It is suitable to use as a dietary supplement or health food by coating with a coating agent such as carboxymethylcellulose and forming into a capsule or processing into a beverage (drink) form. That. In particular, tablets, capsules and drinks are desirable. In addition, the content and intake of the skin beautifying agent of the present invention contained in these foods and drinks are almost the same as in the case of the aforementioned oral composition.

The pharmaceuticals and quasi-drugs using the skin beautification agent of the present invention appropriately add known excipients and additives that are pharmaceutically acceptable within the scope of the present invention to the oral skin beautification promoter. These can be processed into conventional preparations such as tablets, capsules, granules, powders, and liquids. This is orally administered and applied for the prevention or treatment of dryness, loss of elasticity, rough skin and the like. In addition, the content and intake of the skin beautifying agent of the present invention contained in these pharmaceuticals and quasi drugs are based on the above-mentioned oral composition.

In addition, in order to apply the skin beautifying agent of the present invention to pet food and livestock feed, as in the case of the foods and drinks, it is blended into various known feeds and drinking water, or tablets together with known raw materials and additives. Can be processed into a pharmaceutical form such as a powder, a granule, and a capsule. The content and intake of the skin beautifying agent of the present invention in these feeds are almost the same as in the case of the aforementioned oral composition.

Next, the present invention will be described in detail with reference to examples, but the present invention is not limited thereto. In each example,%, part and ratio are based on mass unless otherwise indicated.

Production Example 1 (Collagen peptide (1))
5 kg of water was added to 1 kg of the skin from which the catfish and bones had been removed, and the mixture was heated to 85 ° C. under normal pressure and stirred for 1 hour to extract gelatin. The gelatin solution was cooled to 50 ° C., proteolytic enzyme was added, and the enzyme reaction was carried out for 2 hours. Thereafter, the enzyme was inactivated and filtered to separate the filtrate. The filtrate was concentrated under reduced pressure, freeze-dried and pulverized to obtain 192 g of collagen peptide (sample 1). When this collagen peptide was subjected to HPLC analysis by a conventional method, the average molecular weight was about 1,000.

Production Example 2 (Collagen peptide (2))
Tilapia scales were treated with 0.1N hydrochloric acid, washed with a large amount of water, and dried in the sun. 8 L of water was added to 1 kg of dried scales, heated to 85 ° C. under normal pressure, and stirred appropriately for 1 hour to extract gelatin. The gelatin solution was cooled to 50 ° C., proteolytic enzyme was added, and the enzyme reaction was carried out for 1 hour. Thereafter, the enzyme was inactivated and filtered to separate the filtrate. The filtrate was concentrated under reduced pressure, freeze-dried and pulverized to obtain 711 g of collagen peptide (sample 2). When this collagen peptide was subjected to HPLC analysis by a conventional method, the average molecular weight was about 5,000.

Production Example 3 (Camellia seed extract (1))
The dried seeds of Izu Oshima Yabutsubaki were coarsely pulverized and steamed, and then pressed to obtain a pressed rice cake in which the compressed oil was separated. 3 kg of water was added to 1 kg of the defatted material, heated to 85 ° C. under normal pressure and stirred appropriately for 1 hour, cooled to room temperature, and filtered to separate the filtrate. 1 L of water was again added to the filtration residue, and after heating, stirring and cooling in the same manner, the filtrate was collected by filtration. Both filtrates were combined, concentrated under reduced pressure, lyophilized and pulverized to obtain 170 g of powdery camellia seed extract (sample 3) comprising a water-soluble component. As a result of HPLC analysis of this extract by a conventional method, it contained 7.5% Camellia saponin B2, 5.8% Camellia saponin C2, and 2.4% Kaempferol, a kind of flavonol. .

Production Example 4 (camellia seed extract (2))
2 kg of water-containing ethanol (water content 35%) was added to 1 kg of the defatted product obtained in the same manner as in Production Example 3, and the mixture was heated to reflux at 80 ° C. for 1 hour, cooled to room temperature, and filtered to separate the filtrate. To this filtration residue, 2 L of water-containing ethanol (water content 35%) was added again and heated in the same manner. After cooling, the filtrate was collected by filtration. Both filtrates were combined, concentrated under reduced pressure, freeze-dried and pulverized to obtain 12.1 g of a powder (sample 4) containing a water-soluble component. The powder was analyzed by HPLC in the same manner as in Production Example 3. As a result, it contained 8.3% Camellia saponin B2, 5.9% Camellia saponin C2, and 2.6% Kaempferol, which is a flavonol.

Production Example 5 (lipid coating of thioctic acid)
200 g of thioctic acid in crystalline powder (manufactured by Altzchem, Germany, trade name: ALIPURE (registered trademark), racemic), rapeseed hydrogenated oil (manufactured by Kawaken Fine Chemical Co., Ltd., melting point: 67 ° C., flakes) Was mixed well and dispersed uniformly, and then cooled and solidified at room temperature. Next, the solidified product was pulverized with a high-speed mixer, and sieved with 100 mesh (Tyler mesh; the same applies hereinafter) to obtain a thioctic acid lipid coating (sample 5) having a particle size of 150 μm or less.

Production Example 6 (cyclodextrin inclusion product of thioctic acid)
100 g of crystalline thioctic acid (manufactured by Altzchem, Germany, trade name: Alipre (registered trademark), racemate) was dissolved in 500 mL of 50% ethanol, and α-cyclodextrin (manufactured by Wacker Chemie, Germany, trade name: CAVAMAX ( (Registered Trademark) (R) W6) 800 g was added and stirred appropriately, followed by concentration and spray-drying to obtain a cyclodextrin thioctoate inclusion product (sample 6).

Production Example 7 (resveratrol extract)
500 g of sun-dried dried stalks of grapes (Cabernet Sauvignon) were refluxed with 2 L of 70% ethanol solution and filtered to separate the filtrate. To the filtrate residue, 1 L of 70% ethanol was added again and subjected to reflux extraction, followed by filtration to separate the filtrate. Both filtrates were combined and concentrated under reduced pressure, and dextrin was added thereto and spray-dried to obtain 24 g of resveratrol extracted powder (sample 7). As a result of HPLC analysis of the powder by a conventional method, it contained 6.2% of transresveratrol and 6.0% of ε-viniferin.

Test example 1 (blood flow improving effect)
40 subjects (24-65 years old, 20 men, 20 women) who agreed to participate in the study described below were divided into 5 groups per group and blood flow was measured by the double blind method. A test was conducted. First, the subject entered a room of constant temperature and humidity controlled at a temperature of 24 ± 2 ° C. and a humidity of 50 ± 10%, and was allowed to stand quietly for 10 minutes. Thereafter, the blood flow in the back of the hand before taking the test sample was measured using a laser Doppler (Periscan PIMII, manufactured by Perimed). Next, in the control group (placebo group), hard capsules (made of gelatin; the same applies hereinafter) filled with dextrin so that the subject cannot distinguish by color, and in the other groups, hard capsules colored as described above. Each sample filled with each test sample was ingested with 100 mL of water, and after 30 minutes and 60 minutes, the blood flow of the back of the hand was measured again in the same manner as described above. The test sample was the above camellia seed extract (sample 3, sample 4), commercially available thioctic acid, thioctic acid lipid coating (sample 5), resveratrol extract (sample 7), commercially available ginkgo biloba extract. Product (manufactured by BN Co., Ltd.) and carrot extract (manufactured by Maruzen Pharmaceutical Co., Ltd.).

The results are shown in Table 1. In the same table, the numerical values are expressed as average values ± standard deviation (n = 5, ANOVA analysis) as relative values when the value before taking the placebo and the test substance is 100. From the data in Table 1, there was no significant change in blood flow in the back and scalp of the subjects who took placebo, but samples 3 and 4 (camellia seed extract), thioctic acid and sample 5 (thioctic acid) Ingestion of lipid coating) and sample 7 (resveratrol extract) 30 minutes and 60 minutes after ingestion, similar to the intake of ginkgo biloba extract and carrot extract with known blood flow promoting effects It was confirmed that the blood flow value on the back of the hand increased significantly at both later times.

Test Example 2 (Skin fibroblast proliferation promoting action)
The effect on the proliferation of dermal fibroblasts was examined by the following method. That is, normal human adult dermal fibroblasts (manufactured by Kurabo Industries Co., Ltd., NHDF (NB), hereinafter simply referred to as cells) were used with 10% fetal bovine serum (Daiichi Chemical Co., Ltd.) using Petri dishes (φ10 cm). 2 × 10 ⁵ cells were seeded on D-MEM medium (manufactured) supplemented (Sigma, low glucose) and cultured for 4 days until it became sub-confluent (approximately 80% density). Next, the medium is removed, and the cells are washed twice with 5 mL of PBS and further with 5 mL of 0.02% EDTA solution, and then the cells are recovered using 5 mL of 0.25% trypsin solution (manufactured by Nacalai Tesque). After centrifugation (4 ° C., 1,000 rpm, 5 minutes), the supernatant was removed, and the cells were washed twice with PBS to obtain cells. These cells were repeatedly cultured under the above conditions and subcultured.

Using a 96-well cell culture plate (0.32 cm ² , manufactured by Asahi Techno Glass Co., Ltd.), the subcultured cells were treated with a low serum medium for human skin fibroblast proliferation (Kurabo Co., Ltd., skin fibroblasts). 1 × 10 ⁴ cells / well were seeded in 500 mL of basal medium (106S) supplemented with 10 mL of low serum growth additive (LSGS) and cultured for 24 hours. Subsequently, the medium was removed, and the culture was further continued for 48 hours in the low serum medium for human skin fibroblast proliferation to which each sample was added so that the final concentration was 5, 10 or 20 μg / mL. Thereafter, 25 μL of MTT solution (PBS in which thiazolyl blue tetrazolium bromide (manufactured by Sigma, reagent) was dissolved) at a concentration of 5 mg / mL was added and cultured for 1 hour. After completely removing the medium by decantation, formazan solution (25% (v / v) 0.45 M acetate buffer (pH 4.5), 25% (v / v) N, N-dimethylformamide, 10% ( w / v) Contains sodium n-dodecyl sulfate, pH 4.5) was added and stirred. After standing overnight at room temperature, the absorbance at 590 nm was measured to evaluate the degree of cell proliferation. In the above method, the D-MEM medium and the low serum medium for human dermal fibroblast proliferation were supplemented with penicillin (final concentration 100 IU / mL) and streptomycin (final concentration 0.1 mg / mL). All were carried out in a CO ₂ incubator (37 ° C., 5% CO ₂ intensified gas phase). The test samples were the collagen peptide (sample 1, sample 2), camellia seed extract (sample 3, sample 4), commercially available thioctic acid, thioctic acid lipid coating (sample 5), and cyclodextrin thioctoate. Inclusion (sample 6), resveratrol extract (sample 7), commercially available ginkgo biloba leaf extract (manufactured by BN Co., Ltd.), carrot extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) and sample 1 or sample 2 and each sample And combined use.

The results are shown in Table 2, Table 3 and Table 4. In the table, the numerical values are shown as relative values when the value of the control test (when no sample is added) carried out at the same time is taken as 100. In Table 2, samples 1 and 2 were added to the medium so that final concentrations were 50 and 100 μg / mL, and other samples were final concentrations of 5 and 10 μg / mL. In Tables 3 and 4, Sample 1 and Sample 2 were 50 μg / mL, and the other samples were added to the medium by 5 μg / mL.
From the data in Table 2, it was recognized that each sample had a weak effect of growing dermal fibroblasts at each addition concentration.
Further, from the data in Table 3, when Samples 3 to 7 and thioctic acid were used in combination with Sample 1, the effect of synergistically growing fibroblasts was clarified. Furthermore, the proliferation effect was enhanced by using Sample 1, Sample 3, Sample 7, and thioctic acid in combination. However, the effect of increasing fibroblast proliferation could not be confirmed with ginkgo biloba extract and carrot extract.
The effect of increasing fibroblast proliferation was also confirmed from the data in Table 4. However, the proliferation effect tended to be lower than in the case of the data in Table 3.
In addition, as a result of the same test using a collagen peptide having an average molecular weight of about 300 instead of Sample 1 and Sample 2, the effect of promoting the proliferation of fibroblasts by the combination was equal to or more than the tendency of the data in Table 3. (Data omitted).

From the above, it has been clarified that the combination of the collagen peptide according to the present invention and the blood flow improving agent, in particular, camellia extract, thioctic acid, and resveratrol have the effect of significantly promoting the proliferation of human skin fibroblasts. It was.
Although test data is omitted, in this test example, when sample 1 or sample 2 and the three kinds of blood flow improving components are used in combination, human skin is compared to when each is used alone. It was confirmed that the collagen production ability and hyaluronic acid production ability by fibroblasts were remarkably enhanced.

Test Example 3 (Beautiful skin test in humans)
60 volunteer females (35 to 55 years old, average age: 48.6 years old) with reduced skin elasticity and water content who had consented to participate in the study described below, They were divided into names, and each group received each sample and continued for 6 weeks. Before and after ingesting the sample, the skin elasticity is measured using a skin viscoelasticity measuring apparatus (Germany, Courtage + Khazaka, product name: CUTOMETER MPA580 (R)), and moisture of a certain part of the face is measured. The relative moisture value was measured using an apparatus (Corneometer (R) CM825). In addition, this test was done with the said sample 1, sample 3, sample 7, thioctic acid, these combinations, and the ginkgo biloba extract similar to the above. The amount of intake was 5 g for sample 1 and 200 mg for the other samples, and in the case of combination with sample 1, 5 g for sample 1 and 200 mg for the other samples.

The results are shown in Table 5. The skin elasticity and water content before and after ingestion of the sample showed some improvement in the ingestion of each sample other than Ginkgo biloba extract compared to before ingestion. There was no big difference. However, when the samples 1 are combined with each other, the skin elasticity and water content are clearly improved, and the combination of the collagen peptide according to the present invention and the blood flow improving agent, particularly camellia extract, thioctic acids, resveratrol. It has been clarified that when used in combination with a kind, it has an effect of remarkably accelerating skin beautification.

Prototype example 1 (soft capsule)
Sample 1 and Sample 3 (mixing ratio: 10/1), Sample 1 and Sample 7 (mixing ratio: 10/1), Sample 1 and thioctic acid (mixing ratio: 10/1), Sample 1 and Sample 3 and One of Sample 7 and thioctic acid (mixing ratio: 10/1/1/1): 200 parts, Beeswax: 40 parts and evening primrose oil (Efamol, UK): 50 parts are added and mixed by heating. After homogenization, the mixture was applied to a capsule filling machine, and a gelatin-coated soft capsule preparation having an inner volume of 250 mg per one grain was prepared by a conventional method. This capsule preparation can be used as an orally ingestible dietary supplement, pharmaceutical product or animal feed.

Prototype 2 (hard capsule)
Sample 1 and Sample 3 (mixing ratio: 10/1), Sample 1 and Sample 4 and Sample 6 (mixing ratio: 10/3/1), Sample 1, 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) were supplied to a capsule filling machine, and gelatin with an internal volume of 200 mg per grain was prepared by a conventional method. A coated hard capsule formulation was prototyped. This capsule preparation can be used as an orally ingestible dietary supplement, pharmaceutical product or animal feed.

Prototype Example 3 (Beverage)
Sample 1 and sample 3 (mixing ratio: 10/1), sample 1 and sample 7 (mixing ratio: 10/1), sample 1 and thioctic acid (mixing ratio: 10/1) each in 100 mL of commercially available energy drink , 000 mg was added and mixed thoroughly to make a beverage. Even when this was stored in a refrigerator for 6 months, no abnormalities or discomfort was observed in the appearance and flavor. This product can be used as a beverage or drink for improving skin conditions such as dryness, reduced elasticity, and rough skin and / or promoting beautiful skin.

The skin-beautifying agent comprising a combination of the collagen peptide of the present invention and one or more selected from the three specific blood flow-improving agents as an active ingredient is taken or administered orally. By doing so, it has the effect of promoting dryness of skin, reduction of elasticity, improvement of rough skin and / or beautiful skin, and therefore it can be effectively used in the fields of foods and drinks, pharmaceuticals, quasi drugs, feeds and the like.

Claims (13)

1. A skin beautifying agent characterized by containing a collagen peptide and a blood flow improving agent as active ingredients.
2. The skin-beautifying agent according to claim 1, wherein the collagen peptide is a hydrolyzate of collagen or gelatin and has an average molecular weight of about 200 to about 10,000.
3. The blood flow improving agent is one or more selected from the group consisting of camellia seed extract, thioctic acids, resveratrols, and plant extracts containing the resveratrols. The beautiful skin promoter.
4. 4. The skin beautification promoter according to claim 3, wherein the camellia seed extract is an aqueous component obtained by extracting defatted camellia seeds with water and / or a lower alcohol.
5. The camellia seed extract contains saponins, and the saponins include Camellia saponin A1, Camellia saponin A2, Camellia saponin B1, Camellia saponin (Camelia saponin (p. The skin beautification promoter according to claim 3 or 4, comprising one or more selected from the group consisting of (Cameliasaponin) C1 and Camellia saponin (Cameliasaponin) C2.
6. The thioctic acid is one or more selected from the group consisting of thioctic acid, dihydrothioctic acid, their salts, their esters, their amides, and their cyclodextrin inclusions. The skin beautification promoter described in 1.
7. The thioctic acids are one or more crystals, powders and / or selected from the group consisting of thioctic acid, dihydrothioctic acid, salts thereof, esters thereof, amides thereof, and cyclodextrin inclusion products thereof. Or the skin beautification promoter of Claim 3 or 6 which coats the outer surface of particle | grains with lipids.
8. The beautifying agent according to claim 6 or 7, wherein the thioctic acid and / or the dihydrothioctic acid is a racemate.
9. The resveratrol is a composition comprising one or more selected from the group consisting of resveratrol, ε-viniferin, and isomers and / or glycosides thereof. The beautiful skin promoter.
10. The skin beautification promoter according to claim 3, wherein the plant extract containing the resveratrol is obtained from a stem, vine, shoot or flower of a plant belonging to the genus Grapeaceae.
11. An oral composition containing the skin beautification promoter according to any one of claims 1 to 10.
12. The oral composition according to claim 11, wherein the oral composition is a food or drink.
13. A beauty for improving skin conditions such as dry skin, reduced elasticity, rough skin, etc. and / or promoting beautiful skin, characterized by orally ingesting the beautiful skin promoter according to any one of claims 1 to 10. Method.