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HK1193744B - Beautiful-skin-promoting agent and use thereof - Google Patents

Beautiful-skin-promoting agent and use thereof Download PDF

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Publication number
HK1193744B
HK1193744B HK14106739.7A HK14106739A HK1193744B HK 1193744 B HK1193744 B HK 1193744B HK 14106739 A HK14106739 A HK 14106739A HK 1193744 B HK1193744 B HK 1193744B
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HK
Hong Kong
Prior art keywords
skin
acid
resveratrol
extract
camellia
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Application number
HK14106739.7A
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Chinese (zh)
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HK1193744A (en
Inventor
野崎勉
石原健夫
Original Assignee
碧艾奇恩股份有限公司
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Publication of HK1193744A publication Critical patent/HK1193744A/en
Publication of HK1193744B publication Critical patent/HK1193744B/en

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Abstract

The objective of the present invention is to provide a skin beauty enhancer that improves and/or promotes skin condition such as dryness, reduced elasticity, and roughness, an oral composition formed in combination with the skin beauty enhancer for promoting skin beauty, and a cosmetic method for improving skin condition and/or promoting skin beauty.Provided are a combination of collagen peptides and blood flow enhancers as active ingredients, an oral composition formed in combination with the aforementioned beauty enhancers, and a method for orally ingesting the aforementioned beauty enhancers or the aforementioned composition. The blood flow enhancers are particularly selected from the group consisting of camellia seed extract, lipoic acid, resveratrol, and plant extracts containing resveratrol.

Description

Skin-beautifying agent and use thereof
Technical Field
The present invention relates to a skin-beautifying agent, an oral composition containing the same, and a method for using the same. Among these, the skin-care agent is characterized by containing a collagen peptide and a blood flow improver as active ingredients, and is used for improving skin problems such as wrinkles, moisturization, firmness, and sagging of the skin and/or for forming a more beautiful skin.
Background
The skin is composed of epidermis, dermis, and subcutaneous tissue. The epidermis is composed of the stratum corneum, the stratum granulosum, the stratum spinosum, and the stratum basale, and contains a large number of cells such as keratinocytes and melanocytes, thereby preventing invasion of harmful substances or pathogens from the outside or inhibiting water evaporation. The dermis is different from the epidermis in that it has a small number of cells, is occupied by proteins such as collagen and elastin produced by fibroblasts, and extracellular components such as mucopolysaccharides such as hyaluronic acid and chondroitin sulfate, forms a matrix structure, and achieves the following effects: supporting cells and skin tissue, maintaining water in intercellular spaces, maintaining skin lubricity and softness, and protecting skin tissue from external factors derived from ultraviolet rays, dry environment, mechanical irritation or damage, microbial infection, and the like (non-patent document 1).
However, the extracellular matrix components are denatured and decomposed by aging or daily ultraviolet light, and the synthesis amount thereof is also decreased by the decay of fibroblasts. It is known that a decrease in the amount of the extracellular matrix decomposed and synthesized causes various skin problems such as dry skin, rough skin, decreased elasticity and softness, decreased firmness and luster, increased wrinkles, sagging, and dullness. Therefore, in order to improve the skin condition and/or maintain and enhance the beautified skin, it is desired to activate skin cells, supplement components that are decreased by aging or ultraviolet rays, and further enhance the skin cells. In particular, collagen constitutes about 70% of the dry weight of skin tissue, and is closely related to the viscoelasticity of skin. Furthermore, hyaluronic acid is a substance that has a significant influence on the moisture retention of skin tissue, and therefore, it is important to maintain and enhance collagen and hyaluronic acid in skin tissue.
In order to enhance components in skin tissues such as collagen and hyaluronic acid or to inhibit skin aging, various components have been studied, and gelatin and/or collagen degradation products (patent document 1), N-acetylglucosamine (patent document 2), sphingomyelin (patent document 3), genkwanin (patent document 4), raspberry (patent document 5), and the like have been proposed.
However, in order to exhibit the physiological action of the above-mentioned materials in vivo, it is necessary to ingest a large amount, and even after long-term ingestion, the effect of the material is not clear in terms of the individual, and a predetermined effect may not be obtained, and thus the material is rarely effective in terms of practical use. Therefore, there is a need to develop a material or composition effective for promoting the aforementioned beauty.
Here, the blood flow improver is an improver for improving the function of transporting blood to each tissue of a living body. Blood supplies oxygen, nutrients, water, hormones, and the like to peripheral tissues, transports immune cells, discharges metabolites, regulates body temperature, and the like, and plays a very important role in maintaining the functions of living tissues. It is known that the improvement of blood flow can alleviate symptoms such as arteriosclerosis, hypertension, immunity deterioration, alopecia, fatigue, edema, shoulder soreness, chilly sensation, numbness of hands and feet, dark circles around eyes, and dull skin.
Examples of the blood flow-improving substance include ginkgo leaf extract, safflower extract, placenta extract, capsicum extract, capsaicin, ginseng extract, swertia japonica extract, algin, vitamin E and its derivatives (e.g., vitamin E acetate), pantothenic acid and its salts (e.g., calcium salt and sodium salt), glycyrrhizic acid or glycyrrhetinic acid and their salts (e.g., sodium salt and potassium salt), tabasheer extract, arginine and its derivatives (e.g., arginine glutamic acid), nicotinic acid and its derivatives (e.g., methyl ester), rosemary extract, ginger extract, shogaol, gingerol, zingerone, isoflavone, and vitamin B3Curcuma rhizome extract, extract of grape seed, grape leaf, grape stem, rutin extract, and hairFermented rice germ extract, radix Angelicae sinensis extract, Bulbus Allii extract, and fructus Zanthoxyli extract. However, no report has been found on the effect of the combination of these blood flow improving substances and the skin aging inhibitory components on the skin tissue or skin condition.
Documents of the prior art
Patent document
Patent document 1: japanese laid-open patent publication No. 2004-123637
Patent document 2: japanese patent laid-open publication No. 2001-48789
Patent document 3: japanese patent laid-open publication No. 2005-281257
Patent document 4: japanese patent laid-open publication No. 2004-137217
Patent document 5: japanese patent laid-open publication No. 2003-137801
Non-patent document
Non-patent document 1: widely used in the science of skin Care, pp.6-14, (product) shang Hua House, published 1997, 2/25
Disclosure of Invention
Technical problem
In view of the current situation, the present inventors have developed a skin-beautifying agent for improving and/or promoting skin conditions such as dry skin, decreased skin elasticity, rough skin, and the like, and have provided an oral composition for promoting skin beautifying formed by blending the skin-beautifying agent, and a method for improving and/or promoting skin conditions.
Technical scheme
In order to solve the above problems, the present inventors have conducted extensive studies on the relevance between various materials and the skin care, and as a result, have found that a combination of a collagen peptide and a substance having a blood flow improving effect unexpectedly produces a remarkable effect, and that, particularly, in the substance having a blood flow improving effect, at least one selected from camellia seed extract, thioctic acids, resveratrol and a plant extract containing resveratrol is particularly effective when used together with a collagen peptide. Further, they have found that the compound can be effectively used in oral compositions such as foods, drinks, feeds, pharmaceuticals, and non-pharmaceutical products, and have completed the present invention.
That is, the present invention is characterized in that the skin-beautifying agent is formed by containing, as active ingredients, only a blood flow improver and a collagen peptide, the blood flow improver being one or more than two selected from the group consisting of camellia seed extract, resveratrol and a plant extract containing resveratrol. In the skin care agent, the collagen peptide is preferably one or more selected from the group consisting of collagen, gelatin, and a hydrolysate of collagen and gelatin, and the hydrolysate is preferably one having a molecular weight (average molecular weight, the same applies hereinafter) of about 200 to about 10000.
The camellia seed extract is an extract containing an aqueous component obtained by extracting defatted camellia seed meal with water and/or lower alcohol, preferably an extract containing saponins, and the saponins are particularly preferably one or more selected from camellia saponin (camellia saponin) A1, camellia saponin A2, camellia saponin B1, camellia saponin B2, camellia saponin C1 and camellia saponin C2.
The lipoic acid is preferably one or more compounds selected from the group consisting of lipoic acid (including racemates), reduced forms thereof, salts thereof, esters thereof, amides thereof, and cyclodextrin or lipid-coated forms thereof.
Further, the resveratrol is preferably one or more selected from the group consisting of a monomer of resveratrol, a polymer such as-viniferin, and isomers and/or glycosides thereof, and more preferably in the form of an extract of a plant of the family Vitaceae, Polygonaceae, or Leguminosae.
In another feature of the present invention, it is preferable that the substance orally ingested or administered as the aforementioned skin care promoter is an oral composition, and the oral composition is a food or drink. Also, a method for improving skin conditions such as dry skin, reduced elasticity, and rough skin and/or promoting skin beauty, particularly a cosmetic method, by orally ingesting the collagen peptide and the blood flow improver.
Advantageous effects
The skin care agent of the present invention is formed by containing a collagen peptide and a blood flow improver, has excellent stability in quality and the like, remarkably increases the proliferation thereof by acting on skin cells, promotes the production of skin components such as collagen hyaluronic acid, and recovers, maintains and strengthens components in skin tissues. The blood flow improving agent is used together with collagen peptide, especially at least one selected from Camellia seed extract, thioctic acid, and resveratrol. This can prevent and/or improve skin problems such as dryness, roughness, reduction in elasticity or flexibility, reduction in luster, increase in wrinkles, increase in sagging, and increase in dullness of the skin, and further promote skin beauty. The related effects were found to be evident by oral ingestion or administration of the above-mentioned muscle-beautifying promoter. Therefore, the skin care agent can be used effectively in the form of the preparation as it is or in the form of a mixture with various conventional products, particularly in the fields of foods, drinks, feeds, pharmaceuticals, non-pharmaceutical products, and the like. The present invention also provides a cosmetic method for improving skin conditions such as dry skin, reduced elasticity, and rough skin and/or promoting skin beauty by orally ingesting a collagen peptide and a blood flow improving agent.
Detailed Description
The present invention will be described in detail below. First, the skin care agent of the present invention is characterized by containing a collagen peptide and a blood flow improver as active ingredients.
The collagen peptide used in the muscle-building agent of the present invention is a peptide obtained by hydrolyzing collagen obtained by treating a skin, bone, cartilage or tendon of livestock such as cattle, pig, chicken, turkey or ostrich, and a skin, bone, cartilage or scale of fish such as anoectochilus formosanus, salmon, shark, cod, tilapia, nile river perch, carp, sebastic fish, tuna, catfish or eel by a conventional method, or gelatin obtained by thermally denaturing the collagen, with an acid, an alkali or an enzyme. The collagen peptide according to the present invention includes collagen peptides and collagen peptide-containing extracts, and any of the above can be used. The collagen peptide is easily available in the market.
In the present invention, a collagen peptide obtained by hydrolyzing collagen or gelatin and having a molecular weight of about 200 to about 10000, more preferably about 200 to about 5000, and still more preferably about 200 to about 1000 is preferably used.
Furthermore, the blood flow improver of the muscle-beautifying agent of the present invention can use camellia seed extract, thioctic acids, resveratrol, plant extract containing resveratrol, ginkgo leaf extract, safflower extract, placenta extract, capsicum extract, capsaicin, ginseng extract, swertia japonica extract, algin, vitamin E and its derivatives (vitamin E acetate, etc.), pantothenic acid and its salts (calcium salt, sodium salt, etc.), glycyrrhizic acid or glycyrrhetinic acid and their salts (sodium salt, potassium salt, etc.), tabasheer extract, arginine and its derivatives (arginine glutamic acid, etc.), nicotinic acid and its derivatives (methyl ester, etc.), rosemary extract, ginger extract, shogaol, gingerol, zingerone, isoflavone, vitamin B, etc3Turmeric extract, extract of grape seed, leaf, stem, etc., rutin extract, fermented rice germ extract, angelica extract, garlic extract, Japanese pepper extract, etc., and the examples are not limited thereto, and the extract can beOne or more substances having blood flow improving effect are used.
In this connection, the present inventors have conducted further detailed studies on a blood flow improver which can exert a more potent skin-beautifying effect by being used in combination with a collagen peptide, and as a result, have found that an extract of camellia seeds, a lipoic acid compound, and resveratrol or a plant extract containing resveratrol are extremely effective. That is, the preferred muscle-beautifying agent of the present invention is characterized by containing, as the active ingredient, a collagen peptide and one or more kinds selected from the group consisting of camellia seed extract, lipoic acid, resveratrol and a plant extract containing resveratrol.
The camellia seed extract related to the present invention is described in detail below. Camellia japonica refers to Camellia japonica (Camellia japonica) belonging to the Camellia genus (Camellia) of the family Theaceae, and examples thereof include: examples of the plants include but are not limited to, jalapia (c. japonica var. japonica), camellia japonica (c. japonica subsp. rusticana), malus pumila (c. japonica var. macrocarpa), camellia phoenix (c. japonica subsp. ho zenensis), camellia hongkongensis (c. hongkongensis), camellia yunnanensis (c. reticulata), camellia angericae (c. saluensis), camellia southwestern (c. thaliana), camellia sinensis (c. pitardii), and camellia yunnanensis (c. pitardii var. yunnanensis), camellia nitidissima (c. nitissima), camellia wildernifolia (congener with elaeis), camellia sinensis (congener with elaeis), camellia longissima (congener with elaeis), and the like. These camellia plants are preferably those naturally grown or cultivated in the places of the islands in Japan, the peninsula Korea, the peninsula Shandong, China, and the like.
In order to produce the camellia seed extract according to the present invention, it is preferable that the fruit and/or seed of camellia japonica is supplied to a squeezing process, a supercritical extraction process using a hydrophobic organic solvent such as hexane or heptane, or a liquefied gas such as liquefied carbon dioxide or liquefied propane, or the like, and then a defatted substance (hereinafter referred to as defatted meal) as a residue separated by extracting an oil fraction by a conventional method is used as a raw material. Here, the fruit and/or seed of camellia japonica may be either one of a premature fruit and a mature fruit, or seeds thereof may be used, but if a mature fruit or seed thereof is used, the amount of defatted material and/or active ingredient obtained is increased, so this is preferable. More preferably, seeds are used. Preferably, seeds obtained from ripe fruits are dried by sun exposure for about 1 to 2 weeks.
The active ingredient of the camellia seed extract according to the invention is preferably an aqueous ingredient. The aqueous component can be produced by any method using the above-described defatted meal as a raw material, but is preferably subjected to extraction treatment using water and/or a lower alcohol. Since the tendency of extraction of oily substances in the defatted cake increases if the carbon number of the lower alcohol is large, the lower alcohol preferably has a carbon number of at most 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, the water content can be increased in order to suppress extraction of oily components in the defatted cake. For example, the water content is about 20 to about 50 mass% for propanol and about 40 to about 70 mass% for butanol. The extraction solvent is preferably water, methanol and ethanol, or an aqueous alcohol thereof, more preferably water or aqueous methanol or aqueous ethanol having a water content of 50 mass% or more, and still more preferably water.
In the extraction of the defatted meal, about 1 to about 30 times by mass of the above-mentioned extraction solvent is added to 1 part by mass of the defatted meal, and the mixture is stirred and mixed as necessary under normal pressure or pressure of about 1 to about 5 atmospheres at normal temperature to about 120 ℃ for about 10 minutes to about 3 hours, then cooled at normal temperature, filtered, and the filtrate is concentrated and dried by an appropriate method such as reduced pressure drying, spray drying, freeze drying, or the like. The dried product may be appropriately pulverized. Thus, a yellowish to orange solid can be obtained as a water-soluble component contained in the camellia seed of the present invention. The extraction method can increase the amount of the water-soluble component obtained in the present invention by repeating the same extraction treatment on the extraction residue after the primary extraction treatment, or by performing the extraction treatment at about 100 to about 130 ℃ under a pressure of about 1 to about 3 atmospheres, and the extract can be further concentrated and purified by a known means such as solvent fractionation, column fractionation using an adsorbent packed with an ion exchange resin, silica gel, activated alumina, or the like, liquid chromatography separation, or the like. The water soluble component contains saponin, tannin, etc.
Examples of the saponin contained in the water-soluble component include: thesasaponin (S) (3 beta- [ 2-O-beta-D-galactopyranosyl-3-O- (2-O-beta-D-glucopyranosyl-alpha-L-arabinopyranosyl) -beta-D-glucopyranosyloxy ] olean-12-ene-16 alpha, 22 alpha, 28-triol 22- [ (Z) -2-methyl-2-butenoate ] (3 beta- [ 2-O-beta-D- ガラクトピラノシル -3-O- (2-O-beta-D- グルコピラノシル -alpha-L- アラビノピラノシル) -beta-D- グルコピラヌロノシルオキシ ] オレアナ -12- エン -16 alpha, 22 alpha, 28- トリオール 22- [ (Z) -2- メチル -2- ブテノアート ]) is used as Camelliasporin) A1 as 3 beta- [ 2-O-beta-D-galactopyranosyl-3-O- (2-O-beta-D-glucopyranosyl-alpha-L-arabinopyranosyl) -beta-D-glucuronic acid oxygroup ] olean-12-ene-16 alpha, 22 alpha, 28-triol 22- [ (E) -2-methyl-2-butenoate ] (3 beta- [ 2-O-beta-D- ガラクトピラノシル -3-O- (2-O-beta-D- グルコピラノシル -alpha-L- アラビノピラノシル) -beta-D- グルコピラヌロノシルオキシ) オレアナ -12- エン -16 alpha, 22 alpha, camellia saponin (Camellia alasonin) A2 of 28- トリオール 22- [ (E) -2- メチル -2- ブテノアート ]), 3 beta- [ 2-O-beta-D-galactopyranosyl-3-O- (2-O-beta-D-glucopyranosyl-alpha-L-arabinopyranosyl) -beta-D-glucopyranosyloxy ] -16 alpha, 28-dihydroxy-22 alpha- [ [ (Z) -2-methyl-2-butenoyl ] oxy ] olean-12-ene-23-aldehyde (3 beta- [ 2-O-beta-D- ガラクトピラノシル -3-O- (2-O-beta-D- グルコピラノシル -alpha-L- アラビノピラノシル) -beta-D- グルコピラヌロノシルオキシ) ) Camellia saponin (Camelliaison) B1 of-16 alpha, 28- ジヒドロキシ -22 alpha- [ [ (Z) -2- メチル -2- ブテノイル ] オキシ ] オレアナ -12- エン -23- アール as 3 beta- [ 2-O-beta-D-galactopyranosyl-3-O- (2-O-beta-D-glucopyranosyl-alpha-L-arabinopyranosyl) -beta-D-glucopyranosyloxy ] -16 alpha, 28-dihydroxy-22 alpha- [ [ (E) -2-methyl-2-butenoyl ] oxy ] olean-12-ene-23-aldehyde (3 beta- [ [ 2-O-beta-D- ガラクトピラノシル -3-O- (2-O-beta-D- グルコピラノシル -alpha-L- アラビノピラノシル) -beta-D- グルコピラヌロノシル) オキシ ] -16 alpha, 28- ジヒドロキシ -22 alpha- [ [ (E) -2- メチル -2- ブテノイル ] オキシ ] オレアナ -12- エン -23- アール ] camellia saponin (Camellia japonica aponin) B2, 3 beta- [ 2-O-beta-D-galactopyranosyl-3-O- (2-O-beta-D-glucopyranosyl-alpha-L-arabinopyranosyl) -beta-D-glucuronic acid oxy ] olean-12-ene-16 alpha, 22 alpha, 23, 28-tetrol 22- [ (Z) -2-methyl-2-butenoate ] (3 beta- [ 2-O-beta-D- ガラクトピラノシル -3-O- (2-O- beta-D- グルコピラノシル -alpha-L- アラビノピラノシル) -beta-D- グルコピラヌロノシルオキシ ] オレアナ -12- エン -16 alpha, 22 alpha, 23,28- テトラオール 22- [ (Z) -2- メチル -2- ブテノアート ] camellia saponin (Camelliasaponin) C1, and 3 beta- [ 2-O-beta-D-galactopyranosyl-3-O- (2-O-beta-D-glucopyranosyl-alpha-L-arabinopyranosyl) -beta-D-glucopyranosyloxy ] olean-12-ene-16 alpha, 22 alpha, 23, 28-tetrol 22- [ (E) -2-methyl-2-butenoate ] (3 beta- [ 2-O-beta-D- ガラクトピラノシ ] olean-12-ene-16 alpha, 22 alpha, 23, 28-tetraol ル -3-O- (2-O-beta-D- グルコピラノシル -alpha-L- アラビノピラノシル) -beta-D- グルコピラヌロノシルオキシ ] オレアナ -12- エン -16 alpha, 22 alpha, 23,28- テトラオール 22- [ (E) -2- メチル -2- ブテノアート ]) camellia saponin (Camellia alasonin) C2 and the like. These saponins are contained in camellia japonica in particular.
Furthermore, the thioctic acid compounds according to the present invention may be collected and produced by a known method, for example, from natural extracts of bovine or porcine liver or other organs or from chemically synthesized products using ethylene and adipic acid esters as starting materials, without any particular limitation as to the source or type thereof. Here, lipoic acid has asymmetric carbon atoms and thus mirror isomers (R-enantiomer and S-enantiomer) having different optical properties exist, but lipoic acid according to the present invention may be any one of the above individual enantiomers or a mixture of the above enantiomers in any ratio, and may also be a racemate (racemic mixture or racemic compound) (RS-lipoic acid). In the case of industrial production, it is easy to use a commercially available racemate which is inexpensive and readily available. When a racemic modification is used, the effect desired in the present invention tends to be more exhibited, and therefore, it is preferable to use a racemic modification.
The thioctic acid used in the muscle building agent of the present invention may be any of various derivatives other than the above-mentioned lipoic acid, and preferably one or more compounds selected from the group consisting of lipoic acid, reduced forms thereof, salts thereof, esters thereof, amides thereof, and cyclodextrin complexes thereof.
Specific examples of reduced forms of lipoic acid include: dihydrolipoic acid (ジヒドロチオクト acid), dihydrolipoic acid (ジヒドロリポ acid), 6, 8-dimercaptooctanoic acid, RS-dihydrolipoic acid, and the like.
Examples of salts include: potassium salts, sodium salts, calcium salts, and magnesium salts of R-lipoic acid, S-lipoic acid, RS-lipoic acid, R-dihydrolipoic acid, S-dihydrolipoic acid, and RS-dihydrolipoic acid.
Examples of esters include: examples of the organic solvent include partially esterified products or completely esterified products of R-lipoic acid, S-lipoic acid, RS-lipoic acid, R-dihydrolipoic acid, S-dihydrolipoic acid, RS-dihydrolipoic acid, and the like with polyhydric alcohols (monomers or polymers such as ethylene glycol, propylene glycol, butylene glycol, neopentyl glycol, glycerol, erythritol, and polyglycerol), monoesters of glycerin esters (monoglycerides, diglycerides, and triglycerides), and higher alcohols having 10 to 22 carbon atoms (n-decanol, lauryl alcohol, myristyl alcohol, cetyl alcohol, n-octadecanol, isostearyl alcohol, and behenyl alcohol).
Examples of amides include: amides of R-lipoic acid, S-lipoic acid, RS-lipoic acid, R-dihydrolipoic acid, S-dihydrolipoic acid, RS-dihydrolipoic acid, etc.
Examples of cyclodextrin inclusion compounds include: alpha-, beta-, gamma-or-cyclodextrin and the lipoic acid or the derivative thereof.
The present invention is not limited to the above examples.
In the present invention, the thioctic acid compound further includes: the form of the crystal, powder and/or particle, which is selected from the group consisting of one or more kinds of crystals, powders and/or particles of lipoic acid, reduced forms thereof, salts thereof, esters thereof, amides thereof and cyclodextrin complexes thereof, is more preferable from the viewpoint of practical use because the form suppresses thermal denaturation (decomposition, polymerization, discoloration, etc.), moisture absorption or oxidative denaturation of thioctic acids.
The lipids covering the crystal, powder and/or particle outer surfaces of the thioctic acid compounds may be those which are acceptable in the industrial field in which the present invention is used, and may be used alone or in combination with general edible oils and fats or industrial oils and fats, fatty acid glycerides, fatty acids, fatty acid esters, fatty acid amides, higher alcohols, waxes, sterols, glycolipids, phospholipids, and the like. Of the substances listed above, lipids having a melting point of about 30 ℃ or higher are preferable in consideration of handling properties of the coating and physical properties (stability, curability, fluidity, melting properties, solubility, etc.) of the coating. More preferred forms are lipids having a melting point of about 40 ℃ to about 70 ℃, and even more preferred forms are lipids having a melting point of about 40 ℃ to about 60 ℃. If the temperature is less than about 30 ℃, the coating material may not be able to maintain a solid state during its use, may form lumps, or may impair flowability. On the contrary, if it is higher than about 70 ℃, in the production of the inhibitor or composition according to the present invention, there is a risk that the thioctic acid compound itself may be deteriorated due to heat treatment or the influence of mechanical energy.
Specific examples of such lipids include: soybean oil, rapeseed oil, corn oil, melon seed oil, cotton seed oil, wheat germ oil, rice bran oil, sesame oil, olive oil, safflower oil, palm kernel oil, coconut oil, linseed oil, peanut oil, and other vegetable oils and fats, beef tallow, lard, fish oil, and other animal oils and fats, one or more processed oils and fats obtained by subjecting the above oils and fats to one or more treatments such as fractionation, transesterification, decolorization, deodorization, various hardened oils obtained by subjecting the above oils and fats to partial or complete hydrogenation treatment, and 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, arachic acid, behenic acid, and the like) or unsaturated fatty acids (palmitoleic acid, oleic acid, linoleic acid, α -linolenic acid, γ -linolenic acid, behen, Ricinoleic acid, arachidic acid, eicosapentaenoic acid (EPA), erucic acid, docosahexaenoic acid (DHA), and the like), salts of any of the above fatty acids (sodium salt, potassium salt, calcium salt, magnesium salt, and the like), esters with monohydric alcohols (methanol, ethanol, propanol, butanol, and the like), partially or completely esterified products with polyhydric alcohols (non-monomeric polymers such as ethylene glycol, propylene glycol, butylene glycol, neopentyl glycol, glycerol, erythritol, and polyglycerol), glycerides (monoglycerides, diglycerides, and triglycerides), higher alcohols having 10 to 22 carbon atoms (n-decanol, lauryl alcohol, myristyl alcohol, cetyl alcohol, n-octadecanol, isostearyl alcohol, behenyl alcohol, and the like), waxes (palm wax, rice wax (rice bran wax), candelilla wax, and the like), animal-derived waxes such as beeswax, spermaceti, shellac wax, petroleum-derived waxes such as paraffin wax and microcrystalline wax, mineral-derived waxes such as montan wax and ozokerite wax, synthetic waxes such as polyethylene wax and esters of the above fatty acids and the above higher alcohols), sterols (animal cholesterol, plant campesterol, stigmasterol, sitosterol, and the like, ergosterol derived from fungi, and derivatives thereof), glycolipids (monosaccharide diglyceride (モノグルコシルジグリセリド), monogalactosyl diglyceride, disaccharide monoglyceride (ジグルコシルモノグリセリド), digalactosylmonoglyceride (ジガラクトシルモノグリセリド), monosaccharide diglyceride, digalactosyldiglyceride, sucrose fatty acid esters, and the like). It should be noted that the present invention is not limited to the above examples.
In the present invention, any one or a mixture of two or more of the above-mentioned various lipids may be used, but the preferred types of lipids are the above-mentioned edible oils and fats or industrial oils and fats, fatty acid glycerides, fatty acid esters and waxes, more preferably edible oils and fats and fatty acid glycerides, and further more preferably in a form in which they are combined with one or two or more substances selected from fatty acids, higher alcohols, sterols, glycolipids and phospholipids from the viewpoints of adjustment of the melting point of the coating lipid, strengthening of the coating film, and the like.
The crystals, powders and/or particles of thioctic acids can be coated with lipids by a known method. Namely, the following method may be used: a method in which crystals, powders and/or particles of thioctic acid compounds and heated and melted lipids are uniformly mixed and cooled to solidify them and then pulverized using a ball mill, a brush mixer (powder mixer), a V-type mixer, a high-speed paddle mixer, a heating and melting mixer, an ultrasonic wave wet-charging mixer, a drum mixer, a pressure extruder, or the like; a method of coating the thioctic acid compounds in the above form by spraying or dropping the liquid lipids which have been heated as appropriate; the method of mixing the above-mentioned forms of the liponic acids with the particulate lipids under high-speed stirring, and contacting or colliding the two to uniformly adhere and coat the particulate lipids to the entire surface of the crystals, powder and/or particles of the liponic acids. In the present invention, the above method is preferably a method in which crystals, powders and/or particles of thioctic acid compounds and particulate lipids having a specific melting point or higher are mixed by high-speed stirring, and the two are brought into contact or collided with each other to uniformly coat the entire surface of the particulate lipids with the thioctic acid compounds in the above form.
In the coating treatment, it is difficult to control the ratio of the crystals, powders and/or particles of thioctic acid to the lipids to be uniform depending on factors such as the shape or size of the crystals, powders and particles of thioctic acid, the type and melting point of the lipid, and the thickness and properties of the coating film, but the lipid content is generally about 0.05 to about 10 parts by mass, preferably about 0.1 to about 5 parts by mass, per 1 part by mass of the crystals, powders and/or particles of thioctic acid. If the amount of the lipid is less than about 0.05 parts by mass, the coating state is insufficient and the desired effect is hardly exhibited; on the other hand, if it exceeds about 10 parts by mass, the lipoic acid content in the coating material is low, and when the coating material is used, the incorporation ratio is limited, and the practical value may be deteriorated.
Here, the lipid-based coating material of lipoic acid is preferably a material having a form in which the outer surface thereof is coated with a hydrophilic material, regardless of whether or not the coating material is applied to an aqueous composition such as a beverage. Here, the hydrophilic substance is a substance that further coats the outer surface of the lipid-derived coating and can form a coated film having affinity with the aqueous substance, and specific examples thereof include: polysaccharides (xanthan gum, guar gum, tamarind gum, semen plantaginis gum, etc.), starch and chemical starch, yeast cell wall component, glucose, mannan, shellac, sodium alginate, gelatin, carrageenan, amylopectin, carboxymethyl cellulose, soybean protein, whey protein, zein, etc. More preferably one or more selected from the group consisting of polysaccharides, starch, yeast cell wall components, shellac, gelatin, soy protein, zein and mannan; more preferably, one or more selected from the group consisting of yeast cell wall components, shellac and gelatin.
When the coating is carried out by the hydrophilic substance, the method according to the above-mentioned coating method of lipids can be employed. That is, the hydrophilic substance is suitably dissolved in water, ethanol, or another solvent to form a liquid, and the liquid is attached to the outer surface of liponic acids coated with lipids in advance, and then dried to form a coating film of the hydrophilic substance. The coating forms a double-coated structure having a hydrophilic substance as the outermost layer, and when the double-coated structure is used for foods, drinks, feeds, cosmetics, pharmaceuticals, and the like, the affinity with aqueous materials or components is improved, and these can be easily formulated with thioctic acids having low water solubility into a homogeneous composition.
Among the lipid-based coating materials derived from thioctic acids and the double coating materials obtained by further coating the coating materials with a hydrophilic material, a thioctic acid-containing coating material having excellent stability can be obtained by using the following materials in combination, and thus denaturation or deterioration of the thioctic acids due to heat and/or oxidation can be further suppressed, and thus, a thioctic acid-containing coating material having excellent stability is more preferred in the present invention, and the following materials are: one or more selected from the group consisting of Garcinia cambogia pericarp, Cimicifuga racemosa rhizome, Psidium guajava leaf and their extracts (extract obtained by extracting with water and/or hydrophilic organic solvent (lower monohydric alcohol such as ethanol, acetone, etc.), fraction, solvent fraction, or refined extract thereof), and carnitine, more preferably extract of Cimicifuga racemosa rhizome and carnitine, and most preferably carnitine.
The form in which the aforementioned combined raw materials are contained in the aforementioned coat containing thioctic acids may be any of the following forms, or a combination of these forms: (i) the coating material obtained by coating the crystals, powders and/or particles of the thioctic acid with the lipid is mixed with the raw materials used in combination, (ii) the lipid is coated on the mixture of the crystals, powders and/or particles of the thioctic acid and the raw materials used in combination, (iii) the lipid in which a part of the raw materials used in combination is not dispersed and is dissolved is coated on the crystals, powders and/or particles of the thioctic acid, and (iv) the coating material obtained by coating the crystals, powders and/or particles of the thioctic acid with the lipid is coated with the raw materials used in combination and a solution, dispersion or emulsion of the hydrophilic material, and is dried to coat the mixture. In the present invention, the forms (i) and (iv) achieve the effects of the present invention, are easy to manufacture, and have good workability in use of the coating, but the forms (i) and (iii) are apt to exhibit more potent desired effects.
In a related aspect, the ratio of the coating material in which the crystals, powder and/or particles of the thioctic acid compound are coated with the lipid or the lipid and hydrophilic substance to the raw materials for the combination is: the amount of the raw material used in combination is about 0.01 to about 10 parts by mass, more preferably about 0.1 to about 1 part by mass, based on 1 part by mass of the coating. When the amount is less than about 0.01 parts by mass, the improvement in the desired effect by mixing and using the raw materials cannot be recognized; when the amount of the lipoic acid is more than about 10 parts by mass, the content of the lipoic acid in the coating material, particularly in a composition using the coating material, is reduced, and the content of the lipoic acid in various products containing the lipoic acid composition is limited, and the effect expected by the lipoic acid itself cannot be expected in the product stage.
The source or type of resveratrol according to the present invention is not particularly limited, and may be one obtained by a known organic chemical method or one collected and produced using a microorganism, yeast or the like, but is preferably one obtained by extraction from a part of a fruit peel, stem, leaf, vine, sprout, seed, flower, fruit or the like of a plant of the family Vitaceae, Polygonaceae, Leguminosae or the like.
More preferred sources of resveratrol according to the invention are plants of the genus Vitis of the family Vitaceae, the variety of which is not particularly limited, but examples include: eimeran, Aligaster, Wallich, Vioni, Veneri Rieslin, Ottka, Cabernet, Pink, Cancel, Canine, Carlnicarb, Canine, Sinomelo, Lvweitelina, Yao slurry, Zhenna, Jiazhou, Gelunba, Sheno, Sagnan, Mullinguiser, Sasa, Chardonnay, Scheiner, Sambur, Samsung, Changeh, Changesi, Dana, Twinger, Danminna, Dokuito, Danfei, Monnier, Monisa, Prisat, Fuminte, blue Portugal, Muvesa, Markov, Musca, Miller-Turkey, Mile-Turkel, Naviger, Oimei, Marinolo, Martin Roman, Mare, Marvini, Mare Roman, Sagna, Susane, Su Poncide, Suela, Su Pont, Mile-Turkey, Sage, Mira, Mileri-Turkey, Mie, Sage, Mie, Mi, Neomusk, black pakchoi, white pakchoi, peoples, bud rose, melastoma dodecandrum, roman ruby, mefibuhu, three feet in the state of a nail, etc. They can be suitably extracted from various parts of the above-exemplified cultivars, more preferably from stems, vines, sprouts, or flowers, using grapes which naturally grow or grow in chile, japan, italy, france, or the like.
Resveratrol according to the invention may be produced by any method, but may be any of the following: that is, the stem, tendril, sprout, or flower of the grape as exemplified above, or a dried, cut, and pulverized material thereof is used, and the extract is immersed in a solvent for a predetermined time or brought into contact with an extraction solvent under heating and refluxing to obtain an extract solution, and an extract obtained by removing the solvent from the extract solution, a purified product obtained by subjecting the extract to purification treatment such as column chromatography or solvent fractionation using an adsorbent such as silica gel, magnesium silicate, ion exchange resin, activated alumina, cellulose, or activated carbon, and a powdered material obtained by freeze drying, spray drying, or the like are used. In the case of use in food applications, from the viewpoint of convenience and production cost, it is preferable to use a powder obtained by drying and appropriately pulverizing the plant parts, or an extract obtained by extracting fine pieces or powder of the dried product with water or a hydrophilic organic solvent. When the extract is used for pharmaceutical applications, the extract, or purified product with high purity is preferable.
Examples of the hydrophilic organic solvent include: lower monohydric alcohols such as methanol, ethanol, n-propanol and isopropanol, polyhydric alcohols such as propylene glycol, 1, 3-butylene glycol and glycerol, acetone, methyl ethyl ketone, diethyl ether, petroleum ether, ethyl acetate, and their aqueous substances or mixtures thereof. In order to efficiently obtain an extract for producing the desired effect of the present invention, ethanol, acetone, ethyl acetate, and aqueous solutions thereof are preferably used as an extraction solvent. The moisture content of the hydrous matter is, for example, about 1 to about 99% by mass, more preferably about 50% by mass or less in the case of ethanol; in the case of acetone, from about 1 to about 50 mass%, more preferably from about 10 to about 30 mass%; in the case of ethyl acetate, it is about 80 to about 99% by mass, more preferably about 85 to about 95% by mass. If it deviates from the above range, the desired effect of the present invention is reduced or the yield of the extract is reduced.
Resveratrol according to the present invention is directed to a stilbene compound such as trans-resveratrol (monomer of resveratrol), a polymer such as-grape-ine (dimer) and aged polyphenol (trimer), and isomers and/or glycosides thereof. Here, the extract obtained from the plant may contain the above stilbene compounds as the main active ingredients, and may contain quercetin, ellagitannin, ellagic acid, minerals (e.g., potassium, calcium, phosphorus, magnesium), and vitamins.
In the present invention, the blood flow improver used in combination with the collagen peptide is contained in an amount of about 0.01 to about 50% by mass, preferably about 0.1 to about 20% by mass, and more preferably about 0.5 to about 10% by mass of the whole of the skin beautifying agent. If the amount is less than about 0.01% by mass, the effect by the combination is small, whereas if the amount exceeds about 50% by mass, a more desirable effect cannot be expected. The blood flow improver may be any of the known substances or extracts described above, alone or in combination, but preferably includes one or more selected from camellia seed extract, lipoic acid, resveratrol and a plant extract containing resveratrol, and more preferably includes all of the substances described above. The ratio (on a mass basis) when two or more of camellia seed extract, thioctic acids, resveratrol, and resveratrol-containing plant extract are used together is approximately: the camellia seed extract/lipoic acid is 20/80-30/70, and more preferably 60/40-40/60; the camellia seed extract/resveratrol is 99/1-30/70, and more preferably 80/20-50/50; the content of the thioctic acids/resveratrol is 99/1-30/70, and more preferably 80/20-50/50; the blood flow improver is contained in an amount of about 1 mass% or more, more preferably about 10 mass% or more, based on the total amount of the muscle-building agent, with respect to the camellia seed extract/lipoic acid/resveratrol. In the case of a plant extract containing resveratrol, the content of resveratrol in the extract can be set in consideration of the content of resveratrol in the extract.
The muscle-beautifying agent can be used as it is, in the form of powder, solid, paste or liquid comprising only the above active ingredients, using a combination of a collagen peptide and a blood flow improver (particularly, one or more selected from camellia seed extract, lipoic acid, resveratrol and resveratrol-containing plant extract) as the active ingredient, and can be used in foods, beverages, pharmaceuticals, non-pharmaceuticals, feeds, and the like.
The skin care agent of the present invention can be used as an oral composition by incorporating the agent in a general method, suitably in combination with additives known for the above-mentioned uses in which the agent can be used. Here, the known additives may be those generally used for oral ingestion, and for example, additives such as excipients, binders, disintegrants, glidants, wetting agents, fluidizing agents, preservatives, surfactants, stabilizers, diluents, dissolving agents, tonicity agents, bactericides, preservatives, flavoring agents, deodorizing agents, coloring agents, and flavors can be used. Further, the present invention is not limited to the substances described in the above prior art documents, and may be used in combination with known components having a muscle-beautifying effect and/or a blood flow-improving effect or raw materials containing the components. The skin care agent of the present invention can be used as a part of a raw material for blending various products in the fields of foods, drinks, pharmaceuticals, non-pharmaceutical products, feeds, and other industries. Particularly preferably, as a product for beauty or the like.
When the muscle-building agent of the present invention is used in combination with known additives as an oral composition, the composition may be in the form of oral preparations such as powder, granule, tablet, capsule, and liquid. The content of the active ingredient in the oral composition is not always the same depending on the kind and content of the raw materials used in combination, but is generally about 0.1 to 100% by mass, and more preferably about 10 to 100% by mass. If the above content is less than about 0.1 mass%, the desired effect of the present invention will not be recognized. The skin care agent of the present invention is used by a method of oral ingestion or administration. In this case, the suitable intake amount or administration amount of the composition for oral administration of the present invention is based on: based on the above-mentioned active ingredient contained in the preparation, about 100mg to about 100000mg, preferably about 500mg to about 10000mg, and more preferably about 1000mg to about 5000mg per day is given to an adult (50 kg body weight).
The skin care agent of the present invention can be used as a part of a blending material of a known product such as a food, drink, pharmaceutical product, non-pharmaceutical product, feed, or the like. A practical product is described below, but the present invention is not limited in any way by this example.
Specific examples of the food and drink include: beverages such as vegetable juice, fruit juice beverage, refreshing beverage, and tea; cake premix products, snacks such as bread, cake, chocolate, candy, gummy candy, chewing gum, etc.; miso, soy sauce, mayonnaise, barbecue paste, sauce, etc.; instant noodles, udon noodles, buckwheat noodles, pasta, etc.; processed food of livestock meat and fish such as ham or sausage; powdered, solid or liquid dairy products such as milk, yogurt, cream, butter, spread, or cheese; various general processed foods such as seasoning food sprinkled on rice, hamburger, croquette, seafood, jam, jelly, pudding, salad dressing, vegetable cream, and macchia, and nutritional supplementary foods in the form of powder, granule, pill, tablet, soft capsule, hard capsule, paste, or liquid, specific health products, functional foods, health foods, and foods for treating high-density liquid diet or dysphagia.
In the production of these foods and beverages, the skin-beautifying agent of the present invention and known materials may be used, or a part of known materials may be replaced with the skin-beautifying agent of the present invention, and the products may be produced by a general method. For example, the muscle-building agent of the present invention may be mixed with an excipient such as blood sugar, glucose, dextrin, lactose, starch or processed products thereof, cellulose powder, and the like, vitamins, minerals, animal and vegetable or fish and shellfish fats and oils, proteins (including animal and vegetable or yeast-derived proteins, hydrolyzed products thereof, and the like), sugars, pigments, flavors, antioxidants, surfactants, other food additives, powders or extracts containing various nutritional functional components, and the like, and processed into a form such as powder, granule, paste, tablet, and the like, or processed into a form of a general processed food as exemplified above by a general method, or a form such as a capsule by coating the mixed powder or liquid with a coating agent such as gelatin, sodium alginate, sodium carboxymethylcellulose, or the like, or processed into a form of a beverage (drink), preferably, it is used as a nutritional supplement or a health food. Particularly, the preferred form is tablet, capsule or drink. The content or intake amount of the muscle-building agent of the present invention contained in these foods and drinks is substantially the same as in the case of the oral composition.
The pharmaceutical and non-pharmaceutical products using the muscle-building agent of the present invention may be prepared into tablets, capsules, granules, powders, liquids and the like by adding pharmaceutically acceptable known excipients or additives to the oral muscle-building agent and processing the mixture by a general method, within a range not departing from the technical idea of the present invention. Is suitable for preventing or treating dryness, elasticity reduction, pachylosis, etc. by oral administration. The content or intake amount of the muscle-beautifying agent of the present invention contained in these pharmaceutical and non-pharmaceutical products is in accordance with the case of the oral composition.
When the skin care agent of the present invention is applied to pet food or livestock feed, it may be incorporated into various known feeds or drinking water, or processed into a dosage form such as a tablet, a granule, a capsule or the like together with known materials or additives, as in the case of the above-mentioned foods and beverages. The content or intake amount of the skin-beautifying agent of the present invention contained in these feeds is approximately the same as that of the above-mentioned composition for oral administration.
Examples
The present invention will be described in detail with reference to examples, but the present invention is not limited to these examples. In each example,%, parts and proportions are on a mass basis unless otherwise specified.
Production example 1 (collagen peptide (1))
5L of water was added to 1kg of skin from which the body and bones of catfish were removed, and the mixture was heated to 85 ℃ under normal pressure and then stirred appropriately for 1 hour to extract gelatin. The gelatin solution was cooled to 50 ℃ and a proteolytic enzyme was added to carry out an enzymatic reaction for 2 hours. Then, the enzyme was inactivated, and the filtrate was separated after filtration. The filtrate was concentrated under reduced pressure, freeze-dried and pulverized to obtain 192g of collagen peptide (sample 1). The collagen peptide was analyzed by HPLC by a general method, and the average molecular weight was about 1000.
Production example 2 (collagen peptide (2))
After the scales of the tilapia are treated by 0.1N hydrochloric acid, the scales are washed by a large amount of water and dried by sunlight. 8L of water was added to 1kg of the dried scale, and the mixture was heated to 85 ℃ under normal pressure and then stirred appropriately for 1 hour to extract gelatin. The gelatin solution was cooled to 50 ℃ and a proteolytic enzyme was added to carry out an enzymatic reaction for 1 hour. Then, the enzyme was inactivated, and the filtrate was separated after filtration. The filtrate was concentrated under reduced pressure, freeze-dried and pulverized to obtain 711g of collagen peptide (sample 2). The collagen peptide was analyzed by HPLC by a general method, and the average molecular weight was about 5000.
Production example 3 (Camellia seed extract (1))
The dry seeds of Eisenia longissima produced in Isatis glauca are coarsely ground and cooked, and then squeezed to obtain squeezed dregs from which squeezed oil is separated. To 1kg of the defatted material was added 3L of water, and the mixture was heated to 85 ℃ under normal pressure, stirred appropriately for 1 hour, cooled to room temperature, filtered, and the filtrate was separated. After 1L of water was added again to the filtration residue, the mixture was heated, stirred, cooled in the same manner, and then filtered to collect a filtrate. Mixing the two filtrates, concentrating under reduced pressure, freeze drying, and pulverizing to obtain 170g of powdered Camellia seed extract (sample 3) composed of water soluble components. The extract was analyzed by HPLC using a general method, and contained 7.5% camellin B2, 5.8% camellin C2, and 2.4% kaempferol as a flavonoid.
Production example 4 (Camellia seed extract (2))
To 1kg of the defatted material obtained by the same treatment as in production example 3 was added 2L of hydrous ethanol (water content: 35%), and the mixture was refluxed at 80 ℃ for 1 hour, then cooled to room temperature, filtered, and the filtrate was separated. After 2L of hydrous ethanol (water content: 35%) was added again to the filtration residue, the mixture was heated and cooled in the same manner, and then filtered to collect a filtrate. The two filtrates were combined, concentrated under reduced pressure, freeze-dried and pulverized to obtain 12.1g of a water-soluble component-containing powder (sample 4). The HPLC analysis of this powder as in production example 3 gave the following results: contains 8.3% of camellin B2, 5.9% of camellin C2, and 2.6% of kaempferol as one of flavonoids.
Production example 5 (lipid coating of lipoic acid)
200g of hydrogenated rapeseed oil (manufactured by Kagaku Kogyo, Ltd.; Kagaku, ファインケミカル, Kagaku Co., Ltd.; melting point: 67 ℃ C., in the form of a sheet) was added to 330g of crystalline powder of lipoic acid (manufactured by Kagaku Kogyo, ドイツ & アルツケム, trade name: ALIPURE, racemic modification) and melted, and the mixture was thoroughly mixed and dispersed uniformly, followed by cooling and solidification at room temperature. Then, the solidified material was pulverized by a high-speed mixer and sieved through a 100-mesh sieve (taylor mesh, the same shall apply hereinafter) to obtain a lipoic acid lipid coating material (sample 5) having a particle diameter of 150 μm or less.
Production example 6 (Cyclodextrin clathrate of lipoic acid)
100g of lipoic acid (trade name: ALIPURE (registered trademark), racemic body, available from Layu, Germany, Inc. (ドイツ & アルツケム Co.) was dissolved in 500mL of 50% ethanol, and 800g of α -cyclodextrin (trade name: CAVAMAX (registered trademark), available from Wacker chemical Co., Germany, ドイツ & ワッカーヘミー Co., Ltd.) (R) W6) was added thereto, followed by stirring, concentration and spray drying to obtain a liponic acid cyclodextrin clathrate (sample 6).
Preparation example 7 (resveratrol extract)
A dried sunshine of the stem of grape (Cabernet Sauvignon) (500 g) was extracted by refluxing with 2L of a 70% ethanol solution, and then the filtrate was separated by filtration. The filtrate was separated by adding 1L of 70% ethanol again to the filtration residue, and performing reflux extraction. The two filtrates were combined, concentrated under reduced pressure, added with dextrin and spray-dried to obtain 24g of a resveratrol extract (sample 7). The results of HPLC analysis of the powder by the general method were: contains trans-resveratrol 6.2% and viniferin 6.0%.
EXAMPLE 1 (blood flow improving action)
40 subjects (24-65 years old, 20 males and 20 females) who had been approved to participate in the following experiments were grouped into 5 groups, and blood flow measurement experiments were performed according to the double blind test method. First, the subject was allowed to enter a constant temperature and humidity room in which the temperature was controlled to 24. + -. 2 ℃ and the humidity was controlled to 50. + -. 10%, and the room was allowed to stand quietly for 10 minutes. Then, the blood flow rate of the back of the hand before the test sample was taken was measured by using a laser doppler (PeriScan PIMII, manufactured by welengi corporation). Next, in a control group (placebo group), the subject was ingested with 100mL of water into a hard capsule filled with dextrin in a hard capsule (made of gelatin, the same applies hereinafter) colored so that the subject could not be discriminated according to the color, and in the other groups, the subject was ingested with 100mL of water into a hard capsule filled with each test sample in the same colored hard capsule, and the blood flow rate of the back of the hand was measured again in the same manner as described above after 30 minutes and 60 minutes. The camellia seed extract (sample 3 and sample 4), the commercially available lipoic acid, lipoic acid lipid coating (sample 5), resveratrol extract (sample 7), commercially available ginkgo leaf extract (manufactured by yuma biotechnology company (ビーエイチエヌ strain)) and ginseng extract (manufactured by pill-producing pharmaceutical company (pill-producing corporation)) were used as test samples.
The results are shown in Table 1. In the table, the numerical values are relative values when the values before taking the placebo and the test substance are taken as 100, and are expressed by mean values ± standard deviation (n ═ 5, ANOVA analysis). From the data in table 1, it could not be considered that the blood flow volume of the back of the hand and the scalp of the subject who ingested the placebo changed significantly, but when the samples 3 or 4 (camellia seed extract), lipoic acid or 5 (lipoic acid lipid-coated substance), and 7 (resveratrol extract) were ingested, the blood flow promoting effect was as similar to that when the ginkgo leaf extract or ginseng essence was ingested, and the blood flow volume value of the back of the hand was confirmed to be significantly increased at both times after 30 minutes and 60 minutes of ingestion.
[ TABLE 1 ]
TABLE 1 Effect on blood flow promotion (blood flow) of the dorsum manus
EXAMPLE 2 (skin fibroblast proliferation-promoting action)
Examine by the following methodThat is, adult dermal fibroblasts (produced by Bingpo textile Co., Ltd. (クラボウ) and NHDF (NB), hereinafter simply referred to as "cell") 2 × 10, which are obtained by seeding normal human adult dermal fibroblasts (produced by Bingpo textile Co., Ltd.)) with 10% bovine fetal serum (produced by first Chemicals Co., Ltd. (first Chemicals Co., Ltd.)) supplemented with D-MEM medium (produced by Higemma corporation, シグマ, low blood sugar) using a petri dish (. phi.10 cm)5And cultured for 4 days until becoming nearly confluent (about 80% density). Then, the medium was removed, the cells were washed twice with 5mL of PBS, and then with 5mL of 0.02% EDTA solution, 5mL of the cells were collected with 5mL of 0.25% trypsin solution (manufactured by NACALALI TESSQUE corporation, ナカライテスク (LTD)), and after centrifugation (4 ℃, 1000rpm, 5 minutes), the supernatant was removed, and the cells were washed 2 times with PBS. The cells were repeatedly cultured under the above conditions to perform subculture.
96-well cell culture plates (0.32 cm) were used2Asahi glass company, Asahi テクノグラス K.K., produced by Asahi glass company, produced by Kabushiki Kaisha (クラボウ K.) and seeded with 1 × 10mL of a Low Serum Growth Supplement (LSGS) added to 500mL of a skin fibroblast basal medium (106S))4The cells were subcultured for 24 hours per well. Next, the medium was removed, and the human skin fibroblast proliferation low-serum medium to which each sample was added so that the final concentration was 5, 10 or 20. mu.g/mL was further cultured for 48 hours, and then MTT solution (Thiazolum, manufactured by Higemma corporation, シグマ, reagent) was added and dissolved in PBS to a concentration of 5mg/mL) was added and cultured for 25. mu.L for 1 hour. After the medium was completely removed by decantation, 100 μ L of formazan solution (containing 25% (v/v)0.45M acetic acid buffer solution, 25% (v/v) N, N-dimethylformamide, 10% (w/v) sodium lauryl sulfate, pH 4.5) was added and stirred. After standing at room temperature for 1 night, absorbance at 590nm was measured to evaluate the degree of cell proliferation. In the above method, the D-MEM medium and the low serum medium for proliferating human dermal fibroblasts are supplemented with penicillin (final concentration)100IU/mL) and streptomycin (final concentration 0.1mg/mL) in a carbon dioxide incubator (37 deg.C, 5% CO)2In the enhanced gas phase). Here, the collagen peptide (sample 1, sample 2), camellia seed extract (sample 3, sample 4), commercially available lipoic acid, lipoic acid lipid coating (sample 5), cyclodextrin inclusion compound of lipoic acid (sample 6), resveratrol extract (sample 7), commercially available ginkgo leaf extract (manufactured by yoma biotechnology company (ビーエイチエヌ), japan kogaku corporation), carrot extract (manufactured by bocan corporation, and made by bocan corporation), and sample 1 or sample 2 were used together with each sample as test samples.
The results are shown in tables 2, 3 and 4. In the table, numerical values are expressed by relative values when the value of a control test (in the case where no sample is added) performed simultaneously is taken as 100. In Table 2, the final concentrations of sample 1 and sample 2 were 50 and 100. mu.g/mL, and the other samples were added to the medium so that the final concentrations were 5 and 10. mu.g/mL. In tables 3 and 4, sample 1 and sample 2 were 50. mu.g/mL, and the other samples were added to the medium at 5. mu.g/mL, respectively.
It is also considered from the data in table 2 that the effect of each sample on the proliferation of dermal fibroblasts is weak at each additive concentration.
From the data in table 3, when samples 3 to 7 and lipoic acid were used together in sample 1, the effect of synergistically proliferating fibroblast cells became apparent. The proliferation effect was enhanced by using sample 1, sample 3, sample 7 and lipoic acid together. However, the effect of increasing the proliferation of fibroblasts cannot be confirmed for ginkgo biloba extract and carrot extract.
From the data in table 4, the effect of increasing the proliferation of fibroblasts was also confirmed, but the proliferation effect tends to be lower than that in the case of the data in table 3.
The same experiment using a collagen peptide having an average molecular weight of about 300 in place of sample 1 or sample 2 resulted in: the fibroblast proliferation-promoting effect of the co-administered substances was equal to or higher than the tendency of the data in table 3 (data omitted).
[ TABLE 2 ]
TABLE 2 Effect of each sample on the proliferation of dermal fibroblasts
[ TABLE 3 ]
TABLE 3 Effect of combination with sample 1 on fibroblast proliferation
Sample 1 used in combination with the same Absorbance (590nm)
Control 100±3
Sample 3 127±8
Sample No. 4 125±9
Sample 5 120±3
Sample 6 121±4
Sample 7 122±7
Lipoic acid 122±2
Ginkgo leaf extract 105±1
Ginseng extract 106±3
Sample 3+ lipoic acid 146±8
Sample 3+ sample 7 143±8
Lipoic acid + sample 7 141±8
Sample 3+ lipoic acid + sample 7 161±8
[ TABLE 4 ]
TABLE 4 Effect of combination with sample 2 on fibroblast proliferation
Sample 2 used in combination with the same Absorbance (590nm)
Control 100±3
Sample 3 118±4
Sample No. 4 117±6
Sample 5 113±4
Sample 6 114±2
Sample 7 111±5
Lipoic acid 116±5
Ginkgo leaf extract 104±3
Ginseng extract 104±3
Sample 3+ lipoic acid 136±6
Sample 3+ sample 7 132±9
Lipoic acid + sample 7 128±5
Sample 3+ lipoic acid + sample 7 140±9
From the above, it is clear that the combination of the collagen peptide and the blood flow improver according to the present invention, particularly, the camellia extract, the lipoic acid and the resveratrol have a significant effect of promoting the proliferation of human skin fibroblasts.
Although the experimental data are omitted, in the present experimental example, it was confirmed that the ability to produce collagen and the ability to produce hyaluronic acid by human dermal fibroblasts were significantly improved when sample 1 or sample 2 was used in combination with the three blood flow-improving active ingredients as described above, as compared with the case where each of them was used alone.
EXAMPLE 3 (skin test on human)
60 adult women (35-55 years old, average age: 48.6 years old) who had been given consent to the experiments described below and had low skin elasticity and water content were divided into 1 group of 5 groups, and each sample was taken for 6 weeks. Before and after the sample was taken, the skin elasticity was measured with a skin viscoelasticity measuring apparatus (CK corporation, Courage + Khazaka, Germany, trade name: CUTOMER MPA580(R)), and the relative water value was measured with a water measuring apparatus (Corneometer (R) CM825) for the water at a predetermined portion of the face. The experiment was performed using the same ginkgo biloba leaf extract as described above, including sample 1, sample 3, sample 7, lipoic acid, and combinations thereof. The intake amount is: the sample 1 was 5g and the other samples were 200mg, and when combined with the sample 1, the sample 1 was 5g and used together with the other samples, 200 mg.
The results are shown in Table 5. The skin elasticity and water content before and after sample uptake were: in the case where each sample except for ginkgo leaf extract was ingested, some improvement was found after ingestion as compared with before ingestion, but there was no great difference from before ingestion. However, the combination with sample 1 clearly improved the skin elasticity and water content, and it was found that the combination of the collagen peptide and the blood flow improver according to the present invention, particularly, the combination with camellia extract, lipoic acid and resveratrol has a remarkable effect of promoting the skin beauty.
[ TABLE 5 ]
TABLE 5 Effect on human skin (mean. + -. standard error)
Test example 1 (Soft Capsule)
40 parts of beeswax and 50 parts of evening primrose oil (EFAMOL, UK エファモール) were added to 200 parts of any one of the above-mentioned 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: 10/1), sample 1 and sample 3, and sample 7 and lipoic acid (mixing ratio: 10/1/1/1), and the mixture was heated, mixed and homogenized, and then supplied to a capsule filling machine, and a gelatin-coated soft capsule preparation having an internal volume of 250mg per 1 capsule was tried by a general method. The capsule preparation can be used as an orally ingestible nutritional supplement food, a pharmaceutical, or an animal feed.
Test example 2 (hard capsule)
Any of sample 1 and sample 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) was supplied to a capsule filling machine, and a gelatin-coated hard capsule preparation having a volume of 200mg per 1 capsule was tried by a general method. The capsule preparation can be used as an orally ingestible nutritional supplement food, a pharmaceutical, or an animal feed.
Test example 3 (beverage)
To 100mL of a commercial nutritional drink were added: 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: 10/1) were each 1000mL, mixed thoroughly, and then tested as a beverage. Even if the food is stored in a refrigerator for 6 months, no abnormal or unnatural appearance or flavor is observed. The product can be used as a beverage or drink for improving skin conditions such as dryness, reduced elasticity, and rough skin, and/or for promoting skin beauty.
Industrial applicability
The skin-beautifying agent of the present invention, which contains as an active ingredient a collagen peptide together with one or more compositions selected from the above-mentioned three specific blood flow improvers, has an effect of improving skin dryness, decreased elasticity, rough skin and/or promoting skin beautifying by oral ingestion or administration thereof, and therefore can be effectively utilized in the fields of foods and beverages, pharmaceuticals, non-pharmaceuticals, feeds and the like.

Claims (12)

1. A skin-beautifying agent characterized by comprising, as active ingredients, only a collagen peptide and a blood flow-improving agent, wherein the blood flow-improving agent is one or more selected from the group consisting of resveratrol and a plant extract containing resveratrol, or the blood flow-improving agent is one or more selected from the group consisting of resveratrol and a plant extract containing resveratrol, and camellia seed extract and thioctic acid.
2. The muscle-beautifying agent according to claim 1, wherein the collagen peptide is a hydrolysate of collagen or gelatin and has an average molecular weight of 200 to 10000.
3. The skin care agent according to claim 1, wherein the camellia seed extract is an aqueous component obtained by subjecting defatted camellia seed meal to extraction treatment with water and/or a lower alcohol.
4. The muscle-beautifying promoter according to claim 1 or 3, wherein the camellia seed extract is an extract containing saponins selected from one or more of the group consisting of camellia saponin A1, camellia saponin A2, camellia saponin B1, camellia saponin B2, camellia saponin C1 and camellia saponin C2.
5. The muscle-building agent according to claim 1, wherein the lipoic acid is one or more selected from the group consisting of lipoic acid, dihydrolipoic acid, salts thereof, esters thereof, amides thereof, and cyclodextrin inclusion compounds or lipid coating compounds thereof.
6. The muscle-building agent according to claim 1, wherein the lipoic acid is one or more crystals, powders and/or particles of which the outer surface is coated with lipids, the crystals being selected from the group consisting of lipoic acid, dihydrolipoic acid, salts thereof, esters thereof, amides thereof, and cyclodextrin or lipid-coated compounds thereof.
7. The muscle beauty treatment agent according to claim 5 or 6, wherein the lipoic acid and/or the dihydrolipoic acid is racemic.
8. The muscle-beautifying agent according to claim 1, wherein the resveratrol is a composition containing one or more compounds selected from the group consisting of resveratrol, -viniferin, and isomers and/or glycosides thereof.
9. The muscle-beautifying agent according to claim 1, wherein the resveratrol-containing plant extract is obtained by using a stem, a vine, a sprout, or a flower of a plant belonging to the genus Vitis of the family Vitaceae as a raw material.
10. An oral composition comprising the skin care agent as claimed in any one of claims 1 to 9, wherein the blood flow improver is a camellia seed extract and resveratrol or a plant extract containing resveratrol.
11. The oral composition according to claim 10, wherein the oral composition is a food or drink.
12. A cosmetic method for improving and/or promoting the skin condition of dry skin, reduced skin elasticity, and rough skin, comprising orally administering the skin care agent according to any one of claims 1 to 9 or the composition for oral administration according to any one of claims 10 to 11, wherein the cosmetic method does not include a method for treating a skin disease.
HK14106739.7A 2011-04-28 2012-04-26 Beautiful-skin-promoting agent and use thereof HK1193744B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2011-114156 2011-04-28

Publications (2)

Publication Number Publication Date
HK1193744A HK1193744A (en) 2014-10-03
HK1193744B true HK1193744B (en) 2017-12-15

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