CN103501800B

CN103501800B - Beautiful-skin-promoting agent and use thereof

Info

Publication number: CN103501800B
Application number: CN201280020408.4A
Authority: CN
Inventors: 野崎勉; 石原健夫
Original assignee: Bi En Ltd Co
Current assignee: Biaiqien Co., Ltd.
Priority date: 2011-04-28
Filing date: 2012-04-26
Publication date: 2017-01-18
Anticipated expiration: 2032-04-26
Also published as: CN103501800A; JP2012236826A; TWI436774B; JP6205616B2; KR101840508B1; TW201300136A; KR20140027947A; CN107050438A; WO2012147842A1

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-promoagent agent and use thereof

Technical field

The present invention relates to a kind of U.S. flesh accelerator, the composition for oral administration coordinating this U.S. flesh accelerator and being formed and its utilization Method.Wherein, U.S. flesh accelerator is characterised by being formed as effective ingredient containing collagen peptide and improving blood flow agent, uses In the wrinkle to skin, the skin problem that moistens, compact, relaxing etc. improved and/or is used for forming more beautiful skin.

Background technology

Skin is made up of epidermis, corium, subcutaneous tissue.Epidermis is made up of horny layer, granular layer, spinous layer and basal layer, greatly The cell containing keratinocyte, melanocyte etc. for the amount, plays and prevents from extraneous harmful substance or pathogen invasion or press down The effect of moisture evaporation processed.Different from epidermis in the dermis, cell is few, the collagen protein being produced by fiber sprout cell or bullet Property the extracellular components such as the protein of albumen etc., mucopolysaccharide of hyaluronic acid or chondroitin sulfate etc. occupied by, form substrate Structure and realize following acting on: support cell and skin histology, the moisture keeping in intercellular substance, keep skin lubricity and Flexibility, from from ultraviolet, dry environment, mechanical irritation or damage, microorganism infection etc. extrinsic factor protect skin Tissue (non-patent literature 1).

But, above-mentioned extracellular matrix components are affected and degeneration, decomposition by the increase at age or daily ultraviolet, and And decaying according to fiber sprout cell, its synthetic quantity also reduces.It is known that the decomposition of above-mentioned extracellular matrix and synthetic quantity fall Low, xerosis cutiss, pachylosiies, elasticity or flexibility reduction, compact sense or gloss reduction can be caused, increase wrinkle, relax, secretly The various skin problems of light grade.Therefore, in order to improve skin state and/or maintain enhancement beautification skin it is desirable to make skin cell Activation, the supplementary composition because of age increase or ultraviolet minimizing, and so that it is further enhanced.Particularly, collagen protein accounts for skin About the 70% of the dry weight of skin tissue, closely related with the viscoelasticity of skin.And, hyaluronic acid is the guarantor to skin histology The wet material having significant impact, therefore maintain, strengthen skin histology in collagen protein and hyaluronic acid it is critical that.

In order to strengthen the composition in the skin histology with collagen protein or hyaluronic acid as representative, or suppression skin is old Change, have studied various composition so far, be currently suggested analyte (patent documentation 1), the n- acetyl Portugal of gelatin and/or collagen protein Osamine (patent documentation 2), sphingomyelin (patent documentation 3), genkwanin (patent documentation 4), Fructus Rubi (patent documentation 5) etc..

But, the physiological action that above material has to be assumed in vivo, need to absorb in large quantities, even and if Through taken long-term, also and indefinite according to personal effect, and also cannot obtain the situation of desired effectss, energy from practicality The situation enough assuming effectiveness is less.Accordingly, it would be desirable to a kind of material that can effectively facilitate above-mentioned U.S. flesh of exploitation or compositionss.

Here, improving blood flow agent refers to the improvement that the function that blood is transported in each tissue of organism is improved Agent.Blood carries out supplying oxygen supply, nutritional labeling, moisture, hormone etc., carrying immunocyte, discharge metabolite, tune to distal tissues Section body temperature etc., assume responsibility for very important role in the function of bio-tissue maintains.It is known that by improving blood flow, Arteriosclerosis symptom, hypertension symptom, immunity degradation, alopecia symptom, fatigue, edema, shoulder acid, fear of cold, trick can be relaxed The symptom of numbness, black eye or skin dimness etc..

As the material improving blood flow, propose there is such as Ginkgo Biloba Extract, Flos Carthami extract, intacellin, Fructus Capsici Extract, capsaicin, panax ginseng extractum, Japanese Herba Swertiae bimaculatae extract, pheophytin, vitamin e and its derivant (acetic vitamin e Deng), pantothenic acid and its salt (calcium salt, sodium salt etc.), glycyrrhizic acid or enoxolone and their salt (sodium salt, potassium salt etc.), variegated leaf campanilla Tree extract, arginine and its derivant (arginine glutamic acid etc.), nicotinic acid and its derivant (methyl ester etc.), Herba Rosmarini Officinalis extract Thing, Rhizoma Zingiberis Recens extract, shogaol, gingerol, (4-hydroxy-3-methoxyphenyl)ethyl methyl ketone, isoflavone, vitamin b₃, Rhizoma Curcumae Longae extract, the seed of Fructus Vitis viniferae, leaf, stem Deng extract, Extraction of rutin thing, fermentation rice germ extract, Radix Angelicae Sinensis extract, Bulbus Allii extract, Pericarpium Zanthoxyli extract etc.. But, it is not found to study and suppress the combination of composition to skin histology with regard to these improving blood flow materials and above-mentioned skin ageing Or the report of impact that skin state causes.

Prior art literature

Patent documentation

Patent documentation 1: Japanese Unexamined Patent Publication 2004-123637 publication

Patent documentation 2: Japanese Unexamined Patent Publication 2001-48789 publication

Patent documentation 3: Japanese Unexamined Patent Publication 2005-281257 publication

Patent documentation 4: Japanese Unexamined Patent Publication 2004-137217 publication

Patent documentation 5: Japanese Unexamined Patent Publication 2003-137801 publication

Non-patent literature

Non-patent literature 1: Fu Bu road is wide, " science of skin nursing ", page 6～page 14, (strain) skirt China room, 1997 years Distribution in 2 months 25 days

Content of the invention

Technical problem

In view of related present situation, the present inventors are with the description below as problem, i.e. the U.S. flesh accelerator of exploitation to scaly dry skin, The skin state of elastic reduction, pachylosiies etc. is improved and/or is promoted U.S. flesh, provides this U.S. flesh accelerator of cooperation to be formed The composition for oral administration for promoting U.S. flesh and for improving skin state and/or the method promoting U.S. flesh.

Technical scheme

In order to solve above-mentioned problem, the present inventors are carried out repeatedly with keen determination to the relatedness of various materials and U.S. flesh Discussing it was found that collagen peptide and there is the combination of material of improving blood flow effect unexpectedly produce remarkable result, especially Its in the material with improving blood flow effect, from Flos Camelliae Japonicae seed extract, thioctic acid class, resveratrol class and contain white hellebore At least one selecting in the plant extract of alcohols and collagen peptide are used together especially effective.And, it is also found that it was possible to By its effectively utilizes in the Orally administered composition of diet product, feedstuff, pharmaceuticals, non-pharmaceutical products etc., thus completing the present invention.

That is, it is a feature of the present invention that containing only improving blood flow agent and collagen peptide as effective ingredient and forming U.S. Flesh accelerator, this improving blood flow agent is from by Flos Camelliae Japonicae seed extract, resveratrol class and the plant containing described resveratrol class Thing extract constitute group in select one or more.In this U.S. flesh accelerator, collagen peptide be preferably by Collagen protein, gelatin and collagen protein and gelatin hydrolyzable thing composition group in select one or more, on Stating hydrolyzable thing and being preferably its molecular weight (mean molecule quantity, identical below) is about 200～about 10000.

Above-mentioned Flos Camelliae Japonicae seed extract is to carry out extraction process institute containing by water and/or lower alcohol to the defat dregs of rice of Camellia The extract of the water composition obtaining, the preferably extract containing saponinss, this saponins is especially preferably from Tsubaki-saponin (camelliasaponin) a1, Tsubaki-saponin a2, Tsubaki-saponin b1, Tsubaki-saponin b2, Tsubaki-saponin c1 and Tsubaki-saponin In c2 select one or more.

And, thioctic acid class is preferably by thioctic acid (comprising racemic modification), its reduced form, their salt, their ester The one kind or two selecting in the group of compound, their amide and their cyclodextrin clathrate or lipid coating composition Plant above compound.

Further, resveratrol class be preferably from the polymer of the monomer by resveratrol or ε-grape element etc. and it Isomer and/or glucoside composition group in select one or more, more preferably its form be Vitaceae Plant, polygonaceae plant or fabaceous extract.

Other of the present invention are characterised by, the material preferably as orally ingestible or administration above-mentioned U.S. flesh accelerator is oral With compositionss, and this composition for oral administration is diet product.Other are further characterized in that, orally ingestible collagen peptide and improving blood flow Agent and for being improved to the skin state of the drying of skin, elastic reduction, pachylosiies etc. and/or being promoted the side of U.S. flesh Method, especially beauty method.

Beneficial effect

The U.S. flesh accelerator of the present invention is contained collagen peptide and improving blood flow agent and is formed, and the stability of quality etc. is excellent Different, acting on Skin Cell thus significantly improving its propagation, promoting the generation of the skin components of collagen protein hyaluronic acid etc., extensive Composition that is multiple, maintaining, strengthen in skin histology.By by improving blood flow agent especially from Flos Camelliae Japonicae seed extract, thioctic acid class, white Herba chenopodii Reed alcohol apoplexy due to endogenous wind selects at least one and collagen peptide to be used together so as to act on enhancing.Thus, produce following effect, i.e. right The drying of skin, the reduction of coarse, elastic or flexibility, the reduction of gloss, the increase of wrinkle, lax increase, dim increasing Plus the skin problem waiting is prevented and/or improves, and promote U.S. flesh further.Promoted by orally ingestible or administration above-mentioned U.S. flesh Enter agent and significantly find the effect of correlation.Therefore, above-mentioned U.S. flesh accelerator is particularly in diet product, feedstuff, pharmaceuticals, non-medicine In the field of articles for use etc., can directly be carried out for the form of conventional various products effectively with the form of above-mentioned preparation or coordinate Using.And, the present invention provides a kind of orally ingestible collagen peptide and improving blood flow agent and is used for the drying to skin, bullet The skin state of property reduction, pachylosiies etc. is improved and/or is promoted the beauty method of U.S. flesh.

Specific embodiment

The present invention is described in detail below.First, the U.S. flesh accelerator of the present invention is it is characterized in that contain collagen egg White peptide and improving blood flow agent are formed as effective ingredient.

Used in the U.S. flesh accelerator of the present invention, collagen peptide is, by the domestic animal of cattle, pig, chicken, turkey, Ostrichess etc. Skin, bone, cartilage or tendon etc. and Herba Antenoronis filiformiss, salmon, shark, morrhua, tilapia, Nile perch, Cyprinus carpio, butterfish, tuna, The skin of the Fish of Silurus asotus fish, Anguillar japonica etc., bone, cartilage or squama etc. as raw material, to glue obtained from being processed by common method Former albumen or the gelatin obtaining after making this collagen protein thermal denaturation, carry out the peptide of hydrolyzable and gained by acid, alkali or enzyme.? This, in the present invention, described collagen peptide comprises collagen peptide and the extract containing collagen peptide, and can be any Using above-mentioned substance.Utilize commercially available product relatively simple collagen peptide.

In the present invention, it is preferred to use that the collagen peptide after hydrolyzable, its molecule be carried out to collagen protein or gelatin Amount is about 200～about 10000, more preferably about 200～about 5000, more preferably about 200～about 1000.

And, the improving blood flow agent of the U.S. flesh accelerator according to the present invention, can use extract, the thioctic acid of Camellia Class, resveratrol class, the plant extract containing resveratrol class, Ginkgo Biloba Extract, Flos Carthami extract, intacellin, Fructus Capsici extract, capsaicin, panax ginseng extractum, Japanese Herba Swertiae bimaculatae extract, pheophytin, vitamin e and its derivant (acetic vitamin E etc.), pantothenic acid and its salt (calcium salt, sodium salt etc.), glycyrrhizic acid or enoxolone and their salt (sodium salt, potassium salt etc.), variegated leaf campanilla Tree extract, arginine and its derivant (arginine glutamic acid etc.), nicotinic acid and its derivant (methyl ester etc.), Herba Rosmarini Officinalis extract Thing, Rhizoma Zingiberis Recens extract, shogaol, gingerol, (4-hydroxy-3-methoxyphenyl)ethyl methyl ketone, isoflavone, vitamin b₃, Rhizoma Curcumae Longae extract, the seed of Fructus Vitis viniferae, leaf, stem Deng extract, Extraction of rutin thing, fermentation rice germ extract, Radix Angelicae Sinensis extract, Bulbus Allii extract, Pericarpium Zanthoxyli extract etc., And it is not limited to above-mentioned example, can have, using one or more, the material that improving blood flow acts on.

In connection with this, the inventors of the present invention to by with collagen peptide and with and can play more potent That the improving blood flow agent of U.S. flesh facilitation effect carries out further in detail research it was found that the extract of Camellia, thioctic acid class, And resveratrol class or the plant extract containing resveratrol class extremely effective.That is, currently preferred U.S. flesh accelerator Feature be, contain collagen peptide as effective ingredient and from by Flos Camelliae Japonicae seed extract, thioctic acid class, resveratrol class And containing resveratrol class plant extract composition group in select one or more and formed.

The Flos Camelliae Japonicae seed extract being related to the present invention is carried out described in detail below.Flos Camelliae Japonicae refers to belong to Theaceae (theaceae) The Flos Camelliae Japonicae (camellia japonica) of the Flos Camelliae Japonicae system of Camellia (camellia), can enumerate: shallow lake overgrown with wild plants Chinese toon as an example (c.japonica var.japonica), snow mountain tea (c.japonica subsp.rusticana), Fructus Mali Asiaticae Chinese toon (c.japonica var.macrocarpa), phoenix Flos Camelliae Japonicae (c.japonica subsp.hozanensis), Hong Kong Flos Camelliae Japonicae (c.hongkongenesis), Camellia reticulata (c.reticulata), Nujiang Flos Camelliae Japonicae (c.saluenensis), southwestern Flos Camelliae Japonicae class (c.pitardii var.pitardii) and Camellia reticulata class (c.pitardii var.yunnanica), Camellia nitidissima Chi (c.nitidissima), wild Flos Camelliae Japonicae (of the same race with shallow lake overgrown with wild plants Chinese toon), Flos Camelliae Japonicae (of the same race with shallow lake overgrown with wild plants Chinese toon), room long island mountain tea are (same with Fructus Mali Asiaticae Chinese toon Kind) etc..These Flos Camelliae Japonicaes are suitable to be utilized in the local growth naturally such as Japanese Science Society, the Korea peninsula, Shandong Province of China peninsula or cultivation The Flos Camelliae Japonicae becoming.

In order to manufacture Flos Camelliae Japonicae seed extract according to the present invention it is preferable that by the fruit of above-mentioned Flos Camelliae Japonicae and/or seed supply Process to squeezing and employ the hydrophobic organic solvent of hexane or heptane etc. or the liquefaction of liquefied carbon dioxide, liquefied propane etc. In supercritical extraction process of gas etc., then carry out the detached defat thing as residue using oil content is extracted by common method (the hereinafter referred to as defat dregs of rice) are as raw material.Here, the fruit of Flos Camelliae Japonicae and/or seed can be in precocious fruit and mature fruit Any one, it is possible to use their seed, but if using mature fruit or its seed, then defat thing or/and effectively The amount to obtain of composition can become many, therefore preferably this scheme.More preferably use seed.It is preferred that, using to from one-tenth The seed obtaining in ripe fruit was in 1～2 week about, the material that is dried by sunshine etc..

The active component of the Flos Camelliae Japonicae seed extract according to the present invention is preferably water composition.This water composition can be with above-mentioned The defat dregs of rice are manufactured by any means as raw material, but carry out extraction process preferably with water and/or lower alcohol.As The carbon number of fruit lower alcohol becomes big, then lead to the tendency that the oily matter in the defat dregs of rice is extracted can increase, therefore lower alcohol It is preferably carbon number most 5 about, methanol, ethanol, normal propyl alcohol, isopropanol, n-butyl alcohol, isobutanol etc. can be enumerated.Make In the case of the big lower alcohol of carbon number, in order to suppress to extract the oil components in the defat dregs of rice, moisture content can be improved.Example As making moisture content for propanol is about 20～about 50 mass %, and making moisture content for butanol is about 40～about 70 mass %.Preferably Extraction solvent be water, methanol and ethanol and its aqueous alcohol, more preferably water or moisture content are containing of more than 50 mass % Water methanol or aquiferous ethanol, more preferably water.

When extracting the defat dregs of rice, for the said extracted solvent of the defat dregs of rice about 1～about 30 times of quality of addition of 1 mass parts, At ambient pressure or under the pressurization of about 1～about 5 atmospheric pressure, at a temperature of room temperature～about 120 DEG C, about 10 minutes～about 3 hours, After stirring as needed and being mixed, cooled and filtered under room temperature, by drying under reduced pressure, spray drying, freeze-dried etc. Suitable method carries out concentrate drying to filtrate.Suitable pulverization process can also be carried out to this dried object.So can obtain Faint yellow to saffron solid as the water soluble ingredient containing in the camellia seeds of the present invention.Said extracted method is passed through Identical extraction process, or the pressurization in about 1～about 3 atmospheric pressure are repeated to the extraction residue after an extraction process Under, and carry out extraction process at about 100～about 130 DEG C, the amount to obtain of the water soluble ingredient of the present invention can be increased, and, Said extracted thing is carried out further solvent divide carry, the absorption by being filled with ion exchange resin, silica gel, activated alumina etc. The classification of the tubing string of agent, by liquid chromatography separate etc. well-known means and active component can be carried out concentrate essence System.This water soluble ingredient contains saponin, tannic acid etc..

As the saponin containing in above-mentioned water soluble ingredient, can enumerate such as: as 3 β-[2-o- β-d- galactopyranosyl glycosyl- 3-o- (2-o- β-d- glucopyranosyl-α-l- arabopyranose base)-β-d- glucopyranosiduronic acid epoxide] olive- 12- alkene -16 α, 22 α, 28- triol 22- [(z) -2- methyl-2-butene acid esters] (3 β-[2-o- β-d- ガラ Network トピラノシ Le -3-o- (2-o- β-d- グ Le U ピラノシ Le-α-l- アラ PVC ノピラノシ Le)-β - D- グ Le U ピラヌロノシ Le オキシ] オレア Na -12- エ Application -16 α, 22 α, 28- トリオ Le 22- [(z) -2- メチ Le -2- Block テノアト]) Tsubaki-saponin (camelliasaponin) a1, as 3 β-[2-o- β - D- galactopyranosyl glycosyl -3-o- (2-o- β-d- glucopyranosyl-α-l- arabopyranose base)-β-d- glucopyra alditol Acyloxy] olive -12- alkene -16 α, 22 α, 28- triol 22- [(e) -2- methyl-2-butene acid esters] (3 β-[2-o- β - D- ガラ Network トピラノシ Le -3-o- (2-o- β-d- グ Le U ピラノシ Le-α-l- アラ PVC ノピラノシ Le)-β-d- グ Le U ピラヌロノシ Le オキシ) オレア Na -12- エ Application -16 α, 22 α, 28- トリオ Le 22- [(e) -2- メチ Le -2- Block テノアト]) Tsubaki-saponin (camelliasaponin) a2, conduct 3 β-[2-o- β-d- galactopyranosyl glycosyl -3-o- (2-o- β-d- glucopyranosyl-α-l- arabopyranose base)-β-d- pyrrole Glucopyranoside aldehydic acid epoxide] -16 α, 28- dihydroxy -22 α-[[(z) -2- methyl-2-butene acyl group] epoxide] olive -12- alkene - 23- aldehyde (3 β-[2-o- β-d- ガラ Network トピラノシ Le -3-o- (2-o- β-d- グ Le U ピラノシ Le-α-l- アラ PVC ノピラノシ Le)-β-d- グ Le U ピラヌロノシ Le オキシ) -16 α, 28- ジヒ De ロキシ -22 α-[[(z) -2- メチ Le -2- Block テノイ Le] オキシ] オレア Na -12- エ Application - 23- ア Le) Tsubaki-saponin (camelliasaponin) b1, as 3 β-[2-o- β-d- galactopyranosyl glycosyl -3-o- (2- O- β-d- glucopyranosyl-α-l- arabopyranose base)-β-d- glucopyranosiduronic acid epoxide] -16 α, 28- dihydroxy -22 α-[[(e) -2- methyl-2-butene acyl group] epoxide] olive -12- alkene -23- aldehyde (3 β-[[2-o- β-d- ガラ Network トピラノシ Le -3-o- (2-o- β-d- グ Le U ピラノシ Le-α-l- アラ PVC ノピラノシ Le)-β - D- グ Le U ピラヌロノシ Le) オキシ] -16 α, 28- ジヒ De ロキシ -22 α-[[(e) -2- メチ Le -2- Block テノイ Le] オキシ] オレア Na -12- エ Application -23- ア Le) and Tsubaki-saponin (camelliasaponin) b2, as 3 β-[2-o- β-d- galactopyranosyl glycosyl -3-o- (2-o- β-d- glucopyranosyl-α - L- arabopyranose base)-β-d- glucopyranosiduronic acid epoxide] olive -12- alkene -16 α, 22 α, 23,28- tetrol 22- [(z) -2- methyl-2-butene acid esters] (3 β-[2-o- β-d- ガラ Network トピラノシ Le -3-o- (2-o- β - D- グ Le U ピラノシ Le-α-l- アラ PVC ノピラノシ Le)-β-d- グ Le U ピラヌロノシ Le オキシ] オレア Na -12- エ Application -16 α, 22 α, 23,28- テトラオ Le 22- [(z) -2- メチ Le -2- Block テノアト]) Tsubaki-saponin (camelliasaponin) c1 and as 3 β-[2-o- β-d- galactopyranosyl glycosyl -3- O- (2-o- β-d- glucopyranosyl-α-l- arabopyranose base)-β-d- glucopyranosiduronic acid epoxide] olive -12- Alkene -16 α, 22 α, 23,28- tetrol 22- [(e) -2- methyl-2-butene acid esters] (3 β-[2-o- β-d- ガラ Network トピラノシ Le -3-o- (2-o- β-d- グ Le U ピラノシ Le-α-l- アラ PVC ノピラノシ Le)-β - D- グ Le U ピラヌロノシ Le オキシ] オレア Na -12- エ Application -16 α, 22 α, 23,28- テトラオ Le 22- [(e) -2- メチ Le -2- Block テノアト]) Tsubaki-saponin (camelliasaponin) c2 etc..In Flos Camelliae Japonicae Distinguishingly contain these saponinss.

And, according to the thioctic acid class of the present invention, it is originated and species is not particularly limited, can be to cattle or pig The natural extract of the internal organs such as liver, or to synthetic that such as ethylene and adipate ester are initiation material etc., with public affairs The method known carries out the material taken, manufacture.Here, thioctic acid is due to having asymmetric carbon atom, therefore there is optical property Different mirror image isomers (r- enantiomer and s- enantiomer), but can be that any of the above is a kind of according to the thioctic acid of the present invention Single enantiomer or above-mentioned enantiomer are with the mixture of arbitrary proportion, and, can also be racemic modification (racemic mixture Or racemic compound) (rs- thioctic acid).In the industrial production implement when, using cheap and be readily obtained commercially available Racemic modification is relatively simple.Due to when using racemic modification, make the effect preferably embodiment desired by the present invention tendency relatively Greatly, therefore preferably use racemic modification.

Used in the U.S. flesh accelerator of the present invention, thioctic acid class can be suitably using each in addition to above-mentioned thioctic acid Kind of derivant, preferably by thioctic acid, its reduced form, their salt, their carboxylate, their amide and they One or more material is selected in the group of cyclodextrin clathrate composition.

As the specific example of the reduced form of thioctic acid, can enumerate such as: dihydrolipoic acid (ジヒ De ロチオ Network ト acid), Dihydrolipoic acid (acid of ジヒ De ロリ Port), 6,8- dimercapto octanoic acid, rs- dihydrolipoic acid etc..

Can enumerate such as salt: r- thioctic acid, s- thioctic acid, rs- thioctic acid, r- dihydrolipoic acid, s- dihydrolipoic acid, The potassium salt of rs- dihydrolipoic acid etc., sodium salt, calcium salt, magnesium salt etc..

Can enumerate such as ester: make r- thioctic acid, s- thioctic acid, rs- thioctic acid, r- dihydrolipoic acid, s- dihydro sulfur pungent Acid, rs- dihydrolipoic acid etc. and polyhydric alcohol (ethylene glycol, propylene glycol, butanediol, neopentyl glycol, glycerol, erythrol, polyglycereol Deng monomer or polymer) the partial esterification product that formed or complete esterification products or with glyceride type (monoglyceride, glycerol Diester, triglyceride) or be 10～22 with carbon number higher alcohols (Decanol, lauryl alcohol, myristyl alcohol, spermol, N-octadecane alcohol, isooctadecane alcohol, mountain alcohol etc.) monoesters that formed etc..

Can enumerate such as amide: make r- thioctic acid, s- thioctic acid, rs- thioctic acid, r- dihydrolipoic acid, s- dihydro sulfur The amide of octanoic acid, rs- dihydrolipoic acid etc..

Can enumerate such as cyclodextrin clathrate: α-, β-, γ-or δ-cyclodextrin and above-mentioned thioctic acid or it is derivative The clathrate that thing is formed.

It should be noted that the present invention is not limited to above example.

In the present invention, also comprise as thioctic acid class: from by above-mentioned thioctic acid, its reduced form, their salt, they Carboxylate, their amide and their cyclodextrin clathrate composition group in select one or more crystallization, The material that the outer surface of powder and/or particle is coated and formed by lipid, because this form (is divided to the thermal metamorphism of thioctic acid class Solution, polymerization, variable color etc.), moisture absorption or oxidative deformation suppressed, this form more preferred therefore from practicality.

Coat the lipid of the crystallization, powder and/or particle external surface of above-mentioned thioctic acid class, can be to utilize the present invention Industrial field in allow the material using additionally it is possible to general edible oil lipid or iundustrial oil lipid, fatty acid glycerine Esters, fatty acid, fatty acid ester, fatty acid acyl amine, higher alcohols, wax class, steroid, sugared lipid, phospholipid Etc. being utilized alone or in combination.In material listed above, if it is considered that the physical property of the operability of cladding and coating is (stable Property, curable, mobility, meltbility, dissolubility etc.), preferably fusing point is more than about 30 DEG C of lipid.More preferred form It is the lipid that fusing point is about 40 DEG C～about 70 DEG C, further preferred form is the lipid that fusing point is about 40 DEG C～about 60 DEG C Class.If below about 30 DEG C, having coating and be unable to maintain that the situation of solid-state when it uses, form block or damage flowing Property situation occur.Whereas if greater than about 70 DEG C, when manufacturing inhibitor or the compositionss according to the present invention, at heating Reason or the impact of mechanical energy, have the danger that thioctic acid class itself degenerates.

As the specific example of such lipid, can enumerate such as: soybean oil, Oleum Brassicae campestriss, Semen Maydis oil, Semen Benincasae oil, Semen Gossypii Oil, Semen Tritici aestivi germ oil, Testa oryzae oil, Oleum sesami, olive oil, safflower oil, Petiolus Trachycarpi oil, palm kernel oil, Oleum Cocois, Semen Lini oil, Semen arachidis hypogaeae The animal system oils and fatss of department of botany's oils and fatss of oil etc., Adeps Bovis seu Bubali, Adeps Sus domestica, fish oil etc., above oils and fatss are applied with point carry, ester exchange, de- One or more of the process of color, deodorization etc. processing oils and fatss, each of partially or completely hydrotreating has been carried out to above oils and fatss Kind fixed oil, carbon number are 2～22 satisfied fatty acid (acetic acid, butyric acid, caproic acid, octanoic acid, capric acid, lauric acid, Semen Myristicae Acid, pentadecanoic acid, Palmic acid, stearic acid, 12- hydroxy stearic acid, isostearic acid, arachidic acid, behenic acid etc.) or unsaturated fatty acidss Sour (palmitoleic acid, Oleic acid, linoleic acid, alpha-linolenic acid gamma-Linolenic acid, castor oil acid, arachic acid, eicosapentaenoic acid (epa), erucic acid, docosahexenoic acid (dha) etc.), salt (sodium salt, potassium salt, calcium salt, the magnesium salt of any of the above fatty acid Deng) and the esters that formed of monohydric alcohol (methanol, ethanol, propanol, butanol etc.) and polyhydric alcohol (ethylene glycol, propylene glycol, butanediol, The polymer of the non-monomer of neopentyl glycol, glycerol, erythrol, polyglycereol etc.) the partial esterification product that formed or be esterified completely Product or glyceride type (monoglyceride, diglyceride, triglyceride) or be 10～22 with carbon number higher alcohols (just Decanol, lauryl alcohol, myristyl alcohol, spermol, n-octadecane alcohol, isooctadecane alcohol, mountain alcohol etc.), wax class (brown wax, rice wax The wax from plant of (rice bran wax), candelilla wax etc., Cera Flava, spermaceti, shellac wax etc. derive from the wax of animal, paraffin, micro- Brilliant wax etc. derive from oil wax, the wax from mineral of lignite wax, ceresine etc., Tissuemat E, above-mentioned fatty acid and on State the synthetic wax of the ester etc. of higher alcohols formation), steroid (cholesterol of animality, vegetal campesterol, stigmasterol, Sitosterol etc., from ergosterol, their derivant of mushroom), sugared lipid (monosaccharide groups diglyceride (モノグ Le U シ Le ジグリセリ De), monogalactosyl diglyceride, disaccharidase base monoglyceride (ジグ Le U シ Le モノグリセリ De), Double galactose monoglycerides (ジガラ Network トシ Le モノグリセリ De), monosaccharide groups diglyceride, digalactosyl diglyceride, Sucrose fatty acid ester etc.).It should be noted that the present invention is not the invention being limited by above-mentioned example.

Any one or two or more mixture of above-mentioned various lipids can be used in the present invention, it is preferable that The species of lipid is above-mentioned edible oil lipid or iundustrial oil lipid, fatty acid glycerine esters, fatty acid ester and wax Class, more preferably edible oil lipid and fatty acid glycerine lipid, and, the fusing point adjustment from cladding lipid, coating film From the viewpoint of strengthening etc., it is more preferably them and from fatty acid, higher alcohols, steroid, sugared lipid or phospholipid The form that one or more materials that apoplexy due to endogenous wind is selected are combined.

Can be coated by lipid using the outer surface that known method makes crystallization, powder and/or the particle of thioctic acid class. I.e., it is possible to be following methods: using ball mill, scouring type blender (bulk material mixer), V-shaped mixer, high-speed mixer, High speed paddle mixer, heating melting mixing machine, ultrasound wave overly moist liquid adding type mixer, barrel mixer, pressurization extruding machine Deng, so that crystallization, powder and/or the particle of thioctic acid class is uniformly mixed, cool down with the lipid of heating melting and after so that it is solidified The method pulverized；The liquefied lipid spraying after suitable heating will be carried out or dripped and the thioctic acid to above-mentioned form The method that class is coated；The thioctic acid class of above-mentioned form and emboliform lipid are carried out high-speed stirred makes it mix, and leads to Cross and so that both is contacted or collide so that emboliform lipid is uniformly attached to crystallization, powder and/or the particle of thioctic acid class Integral surface and the method that coated.In the present invention, in said method be preferably, by the crystallization of thioctic acid class, powder and/ Or particle carries out high-speed stirred with particle shape lipid more than above-mentioned specific fusing point and so that it is mixed, by making both contact or touching Hit so that emboliform lipid is evenly coated at the method on the integral surface of thioctic acid class of above-mentioned form.

When carrying out above-mentioned cladding and processing, the shape of crystallization, powder and particle according to thioctic acid class or size, lipid Species and fusing point, the thickness of coating film and character etc. factor it is difficult to by the crystallization of thioctic acid class, powder and/or particle with The ratio regulation of lipid is consistent, but generally, for the crystallization of the thioctic acid class of 1 mass parts, powder and/or particle, lipid Class is about 0.05 mass parts～about 10 mass parts, preferably from about 0.1 mass parts～about 5 mass parts.If lipid is less than about 0.05 mass parts, coated state is insufficient and be difficult to embody desired effect；Whereas if exceeding about 10 mass parts, cladding Thioctic acid content in thing is few, is limited by fit rate etc. and occur and damage practical value in the case of using coating Situation.

Here, the coating of the lipid by above-mentioned thioctic acid class, it is applied to beverage etc. with whether there is Situation in water system compositionss is unrelated, still more preferably for making its outer surface by the formed form of close substances in aquatic system cladding Material.Here, described close substances in aquatic system refers to, further cladding from lipid coating outer surface, can be formed and Aqueous substance has the material being wrapped by film of affinity, can enumerate such as a specific example: polysaccharide (xanthan gum, Guar beanss Glue, tamarind gum, plantasan etc.), starch and chemical starch, yeast cell wall component, glucose, mannan, Lac, sea Sodium alginate, gelatin, carrageenan, amylopectin, carboxymethyl cellulose, soybean protein, lactalbumin, zein etc..More excellent Elect as from polysaccharide, starch, yeast cell wall component, Lac, gelatin, soybean protein, zein and mannan composition Group in select one or more；More preferably from the group of yeast cell wall component, Lac and gelatin composition Middle select one or more.

When being coated by related close substances in aquatic system, can be using the method for coating according to above-mentioned lipid Method.That is, above-mentioned parent's substances in aquatic system is made suitably to be dissolved in water, ethanol, form fraction in other solvents so as to be attached to pre- The coating film of close substances in aquatic system can be formed after the first outer surface of thioctic acid class being coated by lipid, drying.Related cladding Thing is formed with close substances in aquatic system for outermost dual cladding structure, is being used in diet product, feedstuff, cosmetics, doctor In the case of medicine etc., improve and the raw material of aqueouss or the affinity of composition, can be easily low with water-soluble by them Thioctic acid class is formulated as homogeneous composition.

In the coating of the lipid from thioctic acid class as above and make this coating further by hydrophilic system In the dual cladding thing of material cladding, so that it is coexisted by them and with following substances, can further suppress sulfur The degeneration of the heat of sad class and/or oxidation or variation, obtain the coating of the lipoic acid class of excellent in stability, therefore at this The thioctic acid class of more preferred relevant form in bright, above-mentioned substance is: from Fructus Resina garciniae peel, red Rhizoma Cimicifugae rhizome, Folium Psidii Guajavae and Their extract is (by the extract of water and/or hydrophilic organic solvent (low-grade monobasic alcohol such as ethanol, acetone etc.), its point Level thing or solvent fraction leach-s/tive or refined thing etc.), carnitine composition group in select one or more, more preferably red The extract of Rhizoma Cimicifugae rhizome and carnitine, most preferably carnitine.

Making the coating of aforesaid lipoic acid class, to contain above-mentioned and with raw material form can be in following form The combination of any one or these forms it may be assumed that (i) make lipid be coated on the crystallization of thioctic acid class, powder and/ Or mix in the coating on particle above-mentioned and with raw material, (ii) by the crystallization of thioctic acid class, powder and/or particle with above-mentioned And carry out on mixed material cladding lipid with raw material, (iii) wraps on the crystallization of thioctic acid class, powder and/or particle Be covered with state and with a part for raw material do not disperseed and made lipid, (iv) that it dissolves the crystallization of thioctic acid class, powder and/ Or lysate, dispersion liquid or the emulsifying of raw material and above-mentioned parent's substances in aquatic system are adhered to and use on the coating of cladding lipid on particle Liquid is simultaneously dried and is coated.In the present invention, the form of (i) and (iv) reaches the effect of the present invention, manufactures easy, coating Use good operability, but the form of (i) and (iii) is easy to embody more potent desired effect.

In related form, the crystallization of thioctic acid class, powder and/or particle have coated lipid or lipid and The coating of close substances in aquatic system with above-mentioned and with the mixed proportion of raw material is: with respect to this coating 1 mass parts, above-mentioned Raw material is about 0.01～about 10 mass parts, even more preferably about 0.1～about 1 mass parts.In the case of less than about 0.01 mass parts, The raising that can obtain desired effect by mixing and with raw material cannot be approved；In the case of exceeding about 10 mass parts, In above-mentioned coating, reduce especially with the thioctic acid content in its compositionss, and then cooperation can be limited and contain thioctic acid Thioctic acid content in the various products of based composition, can cannot expect the desired effect of thioctic acid itself in this product stage Really.

The source of the resveratrol class according to the present invention or species unspecific material, can be known organic chemistrys Method or be the material taken, manufacture using microorganism or yeast etc., but be preferably from Vitaceae, Polygonaceae or bean The material that the position of the peel of the plant of section etc., stem, leaf, climing, sprouting, seed, flower, fruit etc. is extracted and obtained.

As the source of the resveratrol class according to the present invention, more preferred plant is the plant of Vitaceae Vitis, The kind that its kind is not particularly limited to, but for example can enumerate such as: A Yilun, Aligote, Wa get Qi, Viognier, Weir are different Riesling, Ao Tejia, Cabernet Sauvignon, Cabernet franc, Jiamei, beauty's wine, karr Ka Naika, Jiamei's Na, western sieve Norma, green Wei Teli Receive, Traminer, treasure take, Jia state, song rumba, refreshing rope, holy Glan Dinon, Sangiovese, YveSsaintLaurent, Sha Sila, Chardonnay, Bai Shi South, Shi Aibo, Semillon, Sauvignon Blanc, Dynaudio, Ci Weige, red soul, Ta Mingna, cut piece more, red luxuriant and rich with fragrance red, Mo Niyepinuo, general Sa, Fu Er people spy, blue brier grape tooth people, Moschus, Ma Er Visa, Ma Erbaike, mousse card moral, Miller-Tours height, curtain Wei get Er, U.S. Gansu Province, Mario mousse Ka Te, Maas card fourth, admire fondly Fructus Vitis viniferae, peace rue queen consort, Vidal Blanc, Ju Feng, Momotaro Fructus Vitis viniferae, Su Weiweng In vain (セイヴァ Le Block ラ Application), Di Lawa, Niagara, new Moschus, Hei Bake, Bai Bake, Pi Aonai, bud Flos Rosae Rugosae, Rattan is harvested, Rome ruby, Jia Fei road, Jia state three chi etc..They can suitably utilize Chilean, Japanese, Italian, French etc. The Fructus Vitis viniferae that ground naturally grows or cultivates, can extract from each position of the kind of above-mentioned example, more preferably from stem, climing, sprouting Or spend middle extraction.

Resveratrol class according to the present invention can be manufactured by any means, but can be any one in following substances Kind: i.e., using the stem of the Fructus Vitis viniferae of above-mentioned example, climing, sprouting or flower itself or they are dried, chop up, pulverization process Material, and the Extraction solvent in it being impregnated in a solvent the scheduled time or making it and be heated to reflux contacts and extracted Liquid, by remove from this extracting solution solvent extract, this extract carried out using silica gel, magnesium silicate, ion exchange resin, The column chromatography of the adsorbent of activated alumina, cellulose, activated carbon etc. or solvent divide the refined thing of refinement treatment carrying etc. and By these by the material of the method powdered such as freeze-dried, spray drying.In the case of being used in food applications, from convenience From the viewpoint of Manufacturing cost, preferably, the position of above-mentioned plant is dried and suitably pulverize after powder, pass through water Or hydrophilic organic solvent in small, broken bits of this dried object or powder are extracted after extract.And, it is being used in doctor In the case of pharmaceutical product use, preferably said extracted liquid, extract or highly purified refined thing.

Can enumerate such as hydrophilic organic solvent: the low-grade monobasic alcohol class of methanol, ethanol, normal propyl alcohol, isopropanol etc., third The polyalcohols of glycol, 1,3 butylene glycol, glycerol etc., acetone, methyl ethyl ketone, ether, petroleum ether, ethyl acetate and it Aqueous or mixture.It is being efficiently obtained by the extract for producing the effect desired by the present invention, preferably by second Alcohol, acetone, ethyl acetate and their aqueous are as extraction solvent.Moisture to aqueous, for example, in ethanol In the case of, it is about 1～about 99 mass %, below even more preferably about 50 mass %；In the case of acetone, it is about 1～about 50 Quality %, even more preferably about 10～about 30 mass %；In the case of ethyl acetate, it is about 80～about 99 mass %, more preferably It is about 85～about 95 mass %.If disengaging above range, the effect desired by the present invention or the product reducing extract can be reduced Amount.

Resveratrol class according to the present invention is with following compound as object, i.e. the trans-resveratrol (list of resveratrol Body) or ε-grape element (dimer), the polymer going back age polyphenol (trimer) etc. and their isomer and/or glucoside Deng stilbene compound.Here, from the situation of the extract being obtained by above-mentioned plant be using above-mentioned stilbene compound as main Active component, has and comprises Quercetin, elladitannin, ellagic acid, mineral substance (such as potassium, calcium, phosphorus, magnesium), the situation of vitamin class.

In the U.S. flesh accelerator of the present invention, the content with the improving blood flow agent of collagen peptide is that this U.S. flesh promotes About 0.01～about 50 all mass % of agent, preferably from about 0.1～about 20 mass %, more preferably about 0.5～about 10 matter Amount %.If below about 0.01 mass % and little with the effect that causes, conversely, exceed about 50 mass % using also cannot Expect preferably desired effect.It should be noted that improving blood flow agent can be alone or in combination and arbitrarily using above-mentioned public affairs The material known or extract, but it is preferably from Flos Camelliae Japonicae seed extract, thioctic acid class, resveratrol class and contain resveratrol Select in the plant extract of class one or more, more preferably comprise all above-mentioned substances.By Flos Camelliae Japonicae Among seed extract, thioctic acid class, resveratrol class and the plant extract containing resveratrol class two or more together Ratio (quality criteria) in the case of use is substantially: Flos Camelliae Japonicae seed extract/thioctic acid class is 20/80～30/70, more excellent Elect 60/40～40/60 as；Flos Camelliae Japonicae seed extract/resveratrol class is 99/1～30/70, more preferably 80/20～50/50； Thioctic acid class/resveratrol class is 99/1～30/70, more preferably 80/20～50/50；And, to Flos Camelliae Japonicae seed extract/ Thioctic acid class/resveratrol class, the ratio of respective improving blood flow agent is more than about 1 mass % of the total amount of U.S. flesh accelerator, more Plus be preferably containing more than about 10 mass %.It should be noted that in the case of the plant extract containing resveratrol class, Can consider that the content of the resveratrol class in this extract is set.

Above-mentioned U.S. flesh accelerator with collagen peptide and improving blood flow agent (particularly from Flos Camelliae Japonicae seed extract, thioctic acid class, Select in resveratrol class and the plant extract containing resveratrol class one or more) and use thing conduct Effective ingredient, can directly use, i.e. form the powder being only made up of, solid, shaped, pasty state or liquid above-mentioned effective ingredient Form, be used in the purposes of diet product, pharmaceuticals, non-pharmaceutical products, feedstuff etc..

The U.S. flesh accelerator of the present invention, can also suitably and use can be using known interpolation in its such use Thing, makes it contain by conventional method and is utilized as composition for oral administration.Here, known additive can be in order to Orally ingestible and the material that is usually used, for instance, it is possible to using excipient, bonding agent, disintegrating agent, mixed lubrication prescription, wetting agent, fluidisation Agent, preservative agent, surfactant, stabilizer, diluent, lytic agent, tonicity agent, antibacterial, preservative, correctivess, flavoring agent, The substance of coloring agent, spice etc..Further, it is not limited to the material described in above-mentioned prior art literature, also may be used To be used in combination with the known composition with U.S. flesh effect and/or improving blood flow effect or the raw material containing this composition.U.S. of the present invention Flesh accelerator be also used as diet product, pharmaceuticals, non-pharmaceutical products, feedstuff, the various products of other industrial fields cooperation former Material a part and used.It is particularly preferred that as the product for beauty treatment etc..

Using the U.S. flesh accelerator of the present invention and known additive and with and as composition for oral administration in the case of Form, can be the preparations for oral administration of the type for powder agent, granule, tablet, capsule, liquor etc..According to and use raw material Species or content etc. factor it is difficult to specify consistent to the content of the above-mentioned effective ingredient in related composition for oral administration, But substantially 0.1～100 mass % about, more preferably about 10～about 100 mass % about.If above-mentioned content is below about 0.1 mass %, will be unable to approve the desired effect of the present invention.The U.S. flesh accelerator of the present invention passes through orally ingestible or administration Method is utilized.The benchmark of the suitable intake of the composition for oral administration of the present invention in this case or administration amount is: with Based on the above-mentioned effective ingredient containing in this agent, the daily about 100mg～about 100000mg of adult's (body weight 50kg), preferably About 500mg～about 10000mg, more preferably about 1000mg～about 5000mg.

The U.S. flesh accelerator of the present invention can be as the known product of diet product, pharmaceuticals, non-pharmaceutical products, feedstuff etc. The cooperation part of raw material for product and utilized.Hereinafter practical product is described, but the present invention is not subject to this Any restriction of example.

As the specific example of diet product, can enumerate such as: the beverage class of vegetable juice, fruit drink, refreshment drink, tea etc.； The snack categories of cake ready mix product, bread, cake, chocolate, confection, chewing gum, chewing gum etc.；Miso, soy sauce, sauce, egg The flavouring agent of salted and fermented soya paste, barbecue or flour juice etc.；The noodles of instant noodles, Japanese noodle, Semen Fagopyri Esculenti, Italian noodle etc.；Petaso or sausage etc. Poultry meat the flesh of fish processed food；The powder of milk, Yoghourt, butter, butter, taste product or cheese etc., solid, shaped or liquid Milk product；The seasoned food that is sprinkling upon on rice, hamburger, Deep-fried meatballs, seafood are cooked, fruit jam, fruit jelly, pudding, salad dressing, plant Property the various general processed food that drenches etc. of butter, Mai Qi, in addition also powder, graininess, pill shape, tablet shape, soft Capsule shape, ebonite cryptomere, pasty state or liquid dietary supplement, specific health product, functional food, health food, Treatment food of high density liquid food or dysphagia food etc..

When manufacturing these diet products, it is possible to use the U.S. flesh accelerator of the present invention and known raw material, or by this A part for the raw material known to U.S. flesh accelerator displacement of invention, manufactures according to conventional method.For example, as needed By the U.S. flesh accelerator of the present invention and blood glucose, glucose, dextrin, Lactose, starch or its machining object, cellulose powder etc. figuration Agent, vitamin class, the oils and fatss of mineral substance, animals and plants or fish and shellfish, albumen (include protein from animals and plants or yeast, Its hydrolyzable thing etc.), saccharic, pigment, spice, antioxidant, surfactant, other food additives, contain various battalion The edible material of the powder of foster functional component or extracting species etc. is mixed together and is processed as powder, granule, pasty state, tablet etc. Shape, or it is processed as the form of the general processed food of above-mentioned example by conventional method, or pass through gelatin, sodium alginate, carboxylic The covering of sodium carboxymethylcellulose pyce etc. is coated and is formed capsule or be processed as beverage (drink to the powder of mixing or fraction Category) form, utilized preferably as dietary supplement or health food.Be particularly preferably tablet, capsule, The form of potus.It should be noted that the content of U.S. flesh accelerator of the present invention containing in these diet products or intake with The situation of above-mentioned composition for oral administration is roughly the same.

Pharmaceuticals to the U.S. flesh accelerator using the present invention and non-pharmaceutical products, can not violate the technology of the present invention thought In the range of by the known excipient pharmaceutically allowing or additive be added to above-mentioned oral U.S. flesh accelerator in, by typically square Method is processed and the preparation of piece agent, capsule, granule, powder, liquor etc..It is applied to prevention by being administered orally or treat Dry, elastic reduction, pachylosiies etc..It should be noted that the U.S. of the present invention containing in these pharmaceuticals and non-pharmaceutical products The content of flesh accelerator or intake are according to the situation of above-mentioned composition for oral administration.

And, when making the U.S. flesh accelerator of the present invention be applied to pet food or livestock feed, with above-mentioned diet The situation of product is identical, may be fitted in known all feeds or drinking water, or adds together with known raw material, additive Work is the dosage form of tablet shape, graininess, capsule shape etc..The content of the U.S. flesh accelerator of the present invention containing in these feedstuffs Or intake is roughly the same with the situation of above-mentioned composition for oral administration.

Embodiment

Then, the present invention is described in detail to enumerate embodiment, but the present invention is not appointed by these embodiments What limits.In each example, %, part and ratio are removed non-specifically and are marked, and are quality criteria.

Production Example 1 (collagen peptide (1))

In the skin 1kg of the body eliminating Silurus asotus fish and bone add 5l water, under normal pressure, be heated to 85 DEG C after agitation as appropriate 1 Individual hour and extract gelatin.Gelatin solution is cooled to 50 DEG C, adds proteolytic enzyme, carry out 2 hour enzyme reactions.So Afterwards, enzyme is made to inactivate, separating filtrate after filtration.Decompression is lower to concentrate filtrate, carries out freeze-dried and pulverizes, obtains 192g collagen protein Peptide (test portion 1).Hplc analysis is carried out to this collagen peptide by conventional method, mean molecule quantity is about 1000.

Production Example 2 (collagen peptide (2))

After the squama of tilapia being processed by the hydrochloric acid of 0.1n, with massive laundering only so as to sunshine is dried.It is being dried Squama 1kg in add 8l water, under normal pressure, be heated to 85 DEG C after 1 hour of agitation as appropriate and extract gelatin.Gelatin solution is cooled down To 50 DEG C, add proteolytic enzyme, carry out 1 hour enzyme reaction.Then, enzyme is made to inactivate, separating filtrate after filtration.Under decompression Concentrate filtrate, carry out freeze-dried and pulverize, obtain 711g collagen peptide (test portion 2).By conventional method to this collagen egg White peptide carries out hplc analysis, and mean molecule quantity is about 5000.

Production Example 3 (Flos Camelliae Japonicae seed extract (1))

The dry seed originating in the shallow lake overgrown with wild plants Chinese toon on her Dou great island is carried out after coarse pulverization steaming and decocting, carries out squeezing and obtain having separated squeezing The squeezing dregs of rice of oil.Add 3l water in this defat thing 1kg, under normal pressure, be heated to 85 DEG C after after 1 hour of agitation as appropriate, cooling To room temperature, separating filtrate after filtration.Carry out after adding 1l water again in this filtration residue identical heating, stirring, cooling after, Filtered and taken filtrate.Carry out concentrating under reduced pressure, freeze-dried and pulverizing after two kinds of filtrates are merged, obtain being become by water solublity Flos Camelliae Japonicae seed extract (test portion 3) 170g of the powder being grouped into.Hplc analysis is carried out to this extract by conventional method, should Extract contains 7.5% Tsubaki-saponin b2,5.8% Tsubaki-saponin c2, a kind of 2.4% kaempferol as flavonoid.

Production Example 4 (Flos Camelliae Japonicae seed extract (2))

Carry out and defat thing 1kg obtained from Production Example 3 same treatment in add 2l aquiferous ethanol (moisture content 35%), After being heated to reflux 1 hour at 80 DEG C, it is cooled to room temperature, separating filtrate after filtration.2l is added again in this filtration residue Carry out after aquiferous ethanol (moisture content 35%) identical heating, cooling after, filtered and taken filtrate.Two kinds of filtrates are merged Concentrated under reduced pressure afterwards, freeze-dried and pulverize after, obtain powder (test portion 4) 12.1g of containing water-soluble composition.To this powder End carry out with Production Example 3 identical hplc analyze after result be: containing 8.3% Tsubaki-saponin b2,5.9% Tsubaki-saponin c2, A kind of 2.6% kaempferol as flavonoid.

Production Example 5 (the lipid coating of thioctic acid)

Thioctic acid (German Lai Yu company (De イ Star アルツケム society) production, commodity in the crystalline powder of 330g Name: alipure (registered trade mark), racemic modification) (fine chemistry strain is ground in river to the middle 200g hydrogenated rapeseed oil adding heating to melt Formula commercial firm (Off ァイ Application ケミカ Le (strain) is ground in river) produces, fusing point: 67 DEG C, lamellar), be sufficiently mixed and after so that it is uniformly dispersed, It is allowed to cool solidification under room temperature.Then, by homogenizer, this solidfied material is pulverized, by 100 mesh (taylor criteria net Eye, identical below) sieved after obtain the lipoic acid lipid coating (test portion 5) that particle diameter is less than 150 μm.

Production Example 6 (cyclodextrin clathrate of thioctic acid)

Make thioctic acid (German Lai Yu company (De イ Star アルツケム society) production, the commodity of the crystalline powder of 100g Name: alipure (registered trade mark), racemic modification) dissolve in 50% ethanol 500ml, add the alpha-cyclodextrin (Germany of 800g Wacker Chemical Co., Ltd (De イ Star ワッカヘミ society) produces, trade name: cavamax (registered trade mark), (r) w6), suitably So as to concentrating, being spray-dried after stirring, obtain thioctic acid cyclodextrin clathrate (test portion 6).

Production Example 7 (resveratrol extract)

The sunshine dried object 500g of the stem of Fructus Vitis viniferae (Cabernet Sauvignon) is carried out after reflux, extract, by 70% ethanol solution of 2l, Filtered and separating filtrate.The ethanol adding the 70% of 1l in this filtration residue again carries out reflux, extract, is filtered And separating filtrate.Concentrated under reduced pressure after two kinds of filtrates are merged, be spray-dried after adding dextrin wherein, obtain 24g resveratrol extract (test portion 7).By conventional method, the result that this powder is carried out after hplc analysis is: contain 6.2% Trans-resveratrol, 6.0% ε-grape element.

Experimental example 1 (improving blood flow effect)

The subject 40 (24～65 years old, male 20, women 20) that will obtain agreeing to participate in described below experiment It is grouped according to 5 one group, carried out measuring of blood flow experiment according to double blind check method.First, so that subject is entered and control temperature Spend for 24 ± 2 DEG C, the constant temperature and humidity room for 50 ± 10% for the humidity, quiet wait 10 minutes.Afterwards, using Laser doppler seanning (lark prestige company (perimed society) produces, periscan pimii) measures the blood flow of the back of the hand before picked-up experiment test portion. Then, allow in matched group (placebo group) testee with 100ml water absorb together be colored as subject cannot root It is filled with the hard capsule of dextrin in the hard capsule (gelatin system, identical below) being differentiated according to color, allow by reality in other groups The person of testing absorbs the hard capsule being filled with each test test portion in the hard capsule of above-mentioned same colored together with 100ml water, at 30 points Zhong Hou, after 60 minutes, again mensure same as described above is carried out to the blood flow of the back of the hand.It should be noted that by above-mentioned Camellia Extract (test portion 3, test portion 4), commercially available thioctic acid, lipoic acid lipid coating (test portion 5), resveratrol extract (test portion 7), (ball is apt to for commercially available Ginkgo Biloba Extract (You Ma biotech company (PVC エイチエヌ (strain)) production) and panax ginseng extractum Pharmaceutical Co., Ltd (ball is apt to (strain)) produces) as test test portion.

This result is as shown in table 1.In the table, numerical value be using absorb placebo and by the value before Test Materials as Relative value when 100, is indicated (n=5, anova analyze) by meansigma methodss ± standard deviation.From the data of table 1 it is impossible to recognize For intake of the back of the hand of subject and the blood flow significant changes of scalp of placebo, but intake of test portion 3 or test portion 4 (Flos Camelliae Japonicae seed extract), thioctic acid or the situation of test portion 5 (lipoic acid lipid coating) and test portion 7 (resveratrol extract) Under, blood flow facilitation reaches same degree with the situation that intake of Ginkgo Biloba Extract or panax ginseng extractum, after picked-up 30 minutes And two times after 60 minutes, all confirm that the value of the blood flow of the back of the hand significantly increases.

[table 1]

Table 1 promotes the impact of (blood flow) to the blood flow of the back of the hand

Experimental example 2 (skin fiber sprout cell Effect of promoting growth)

Investigate the impact of the propagation to skin fiber sprout cell by the following method.That is, using Petri dish (φ 10cm), in 10% fetal bovine serum (first adding d-mem culture medium (SIGMA company (シグマ society) produces, hypoglycemia) Chemical drugss Co., Ltd. (the first chemicals (strain)) produces) the middle adult skin fiber sprout cell (Cangfu sowing normal person Weaving Co., Ltd. (Network ラボウ (strain)) produces, nhdf (nb).Hereinafter referred merely to as cell.)2×10⁵Individual, culture extremely becomes for 4 days Become closely to converge (about 80% density).Then, remove culture medium, cell is cleaned twice by the pbs of 5ml, then pass through 0.02% Trypsin solution (nacalai tesque Co., Ltd. (Na カライ after edta solution 5ml cleaning cell, with 0.25% テス Network (strain)) produce) 5ml recovery cell, and centrifugation (4 DEG C, 1000rpm, 5 minutes) remove supernatant afterwards, cleaned by pbs Cell is obtained after 2 times.Repeatedly cultivate this cell under these conditions and carry out successive transfer culture.

Using 96 porocyte culture plates (0.32cm², Asahi Glass Co., Ltd's (rising sun テ Network ノグラス (strain)) production), With low blood serum medium, (Kurashiki Boseki K.K.'s (Network ラボウ (strain)) produces application on human skin fibrous bud cell proliferation, in 500ml Skin fiber sprout cell basal medium (106s) in the addition of the low serum of 10ml and breed the culture medium of additive (lsgs)) Middle sowing 1 × 10⁴The above-mentioned successive transfer culture cell in individual/hole, cultivates 24 hours.Then, remove culture medium, make with the addition of The low blood serum medium of above-mentioned application on human skin fibrous bud cell proliferation of each test portion of final concentration of 5,10 or 20 μ g/ml is further continued for training Support 48 hours, afterwards, add mtt solution (to make Thiazolyl blue (SIGMA company (シグマ society) produces, reagent) be dissolved in pbs It is 5mg/ml to concentration) 25 μ l 1 hour of culture.After culture medium being completely removed by decantation, add 100 μ l first solution (comprise 25% (v/v) 0.45m hac buffer, 25% (v/v) n, n- dimethylformamide, 10% (w/v) dodecyl sulfur Sour sodium.Ph value is 4.5) it is stirred.After placing for 1 night under room temperature, measure the absorbance in 590nm, evaluate the propagation journey of cell Degree.It should be noted that in the above-mentioned methods, d-mem culture medium and the application on human skin low blood serum medium of fibrous bud cell proliferation It is as the culture medium that with the addition of penicillin (ultimate density 100iu/ml) and streptomycin (ultimate density 0.1mg/ml), cell is trained Support all CO2 gas incubator (37 DEG C, 5%co₂Strengthening gas phase under) in carry out.Here, above-mentioned collagen peptide (is tried Material 1, test portion 2), Flos Camelliae Japonicae seed extract (test portion 3, test portion 4), commercially available thioctic acid, lipoic acid lipid coating (test portion 5), sulfur The cyclodextrin clathrate (test portion 6) of octanoic acid, resveratrol extract (test portion 7), commercially available Ginkgo Biloba Extract (excellent horse biology skill Art company (PVC エイチエヌ (strain)) produce), Radix Dauci Sativae extract (Maruzen Pharmaceuticals Co., Ltd. (ball be apt to (strain)) give birth to Produce) and test portion 1 or test portion 2 and each test portion be used together as test test portion.

This result is as shown in table 2, table 3, table 4.In this table, numerical value pass through with implement simultaneously controlled trial (without In the case of test portion) value represent as relative value when 100.In table 2, the ultimate density of test portion 1 and test portion 2 be 50 and 100 μ g/ml, and, other test portions are added in the medium, make ultimate density be 5 and 10 μ g/ml.In table 3 and table 4, with Test portion 1 and test portion 2 are 50 μ g/ml, other test portions are respectively added in the medium 5 μ g/ml.

It is also considered as each interpolation concentration from the data of table 2, each test portion makes the effect that skin fiber sprout cell breeds simultaneously Weak.

And, the data from table 3, in the case of being used together test portion 3～7 and thioctic acid, synergistically makes fibre in test portion 1 The effect of dimension sprout cell propagation becomes obvious.By being used together test portion 1 and test portion 3, test portion 7 and thioctic acid, this increasing further Grow effect to be strengthened.But, to Ginkgo Biloba Extract and Radix Dauci Sativae extract it is impossible to confirm to improve the propagation of fiber sprout cell Effect.

From the data of table 4, also confirm to improve the effect of the propagation of fiber sprout cell, but it is believed that with the data of table 3 Situation is compared, and this cultivation effect has the tendency of low.

It should be noted that the collagen peptide replacing test portion 1 or test portion 2 and the use of mean molecule quantity being about 300 is carried out Same experimental result is: the fibrous bud cell proliferation facilitation effect according to being used together thing is with the tendency of the data of table 3 etc. With or higher (omitted data).

[table 2]

The impact of the propagation to skin fiber sprout cell for each test portion of table 2

[table 3]

The impact of table 3 and the propagation combining to fiber sprout cell of test portion 1

Test portion with test portion 1	Absorbance (590nm)
		Comparison	100±3
Test portion 3	127±8
		Test portion 4	125±9
Test portion 5	120±3
		Test portion 6	121±4
Test portion 7	122±7
		Thioctic acid	122±2
Ginkgo Biloba Extract	105±1
		Panax ginseng extractum	106±3
Test portion 3+ thioctic acid	146±8
		Test portion 3+ test portion 7	143±8
Thioctic acid+test portion 7	141±8
		Test portion 3+ thioctic acid+test portion 7	161±8

[table 4]

The impact of table 4 and the propagation combining to fiber sprout cell of test portion 2

Test portion with test portion 2	Absorbance (590nm)
		Comparison	100±3
Test portion 3	118±4
		Test portion 4	117±6
Test portion 5	113±4
		Test portion 6	114±2
Test portion 7	111±5
		Thioctic acid	116±5
Ginkgo Biloba Extract	104±3
		Panax ginseng extractum	104±3
Test portion 3+ thioctic acid	136±6
		Test portion 3+ test portion 7	132±9
Thioctic acid+test portion 7	128±5
		Test portion 3+ thioctic acid+test portion 7	140±9

By above content, specify that the combination of collagen peptide according to the present invention and improving blood flow agent, particularly logical Cross Camellia extract, thioctic acid class, resveratrol have the effect of the significant propagation promoting application on human skin fiber sprout cell.

Here although eliminating experimental data, but in this experimental example, by the blood of test portion 1 or test portion 2 and above-mentioned three kinds Stream improvement result composition situation compared with the situation that it is individually used it is thus identified that by application on human skin fibrous bud thin The ability of the ability of generation collagen protein of born of the same parents and generation hyaluronic acid significantly improves.

Experimental example 3 (the U.S. flesh experiment to people)

To obtain agreeing to participate in described below experiment and skin elasticity and the low volunteer adult female 60 of water quantities (35 years old～55 years old, the mean age: 48.6 years old), by 51 group separately, makes each group absorb each test portion respectively, is continued 6 weeks.? Picked-up test portion before and after with skin determination of viscoelasticity device (Germany, ck company (courage+khazaka society), trade name: Cutometer mpa580 (r)) skin elasticity is measured, and, the moisture determination of water of the predetermined position of face is filled Put (corneometer (r) cm825) and measure moisture relative value.It should be noted that this experiment is with above-mentioned test portion 1, test portion 3, examination Material 7, thioctic acid and combinations thereof, Ginkgo Biloba Extract same as described above and carry out.Intake is: test portion 1 is 5g, removes this Test portion in addition is 200mg, and in the case of combining with test portion 1, test portion 1 is 5g, is made together with test portion 200mg in addition With.

This result is as shown in table 5.Skin elasticity before and after test portion picked-up and water quantities are: extract except Folium Ginkgo intake of In the case of each test portion beyond thing, with picked-up before compared with, find have some improvement result after picked-up, but with picked-up before phase Than no big difference.But, in the case of being respectively combined with test portion 1, skin elasticity and water quantities are substantially improved, clearly The combination of the collagen peptide according to the present invention and improving blood flow agent, especially by with Camellia extract, thioctic acid class, white Veratryl alcohol is used together has significant promotion U.S. flesh effect.

[table 5]

The impact (mean+/-standard error) of the skin to people for the table 5

Study example 1 (soft capsule)

In above-mentioned test portion 1 and test portion 3 (mixing ratio: 10/1), test portion 1 and test portion 7 (mixing ratio: 10/1), test portion 1 and sulfur Octanoic acid (mixing ratio: 10/1), test portion 1 and test portion 3 and test portion 7 and thioctic acid (mixing ratio: any one in 10/1/1/1) 200 Add 40 parts of Cera Flava and 50 parts of Radix Oenotherae erythrosepalae oil (efamol company of Britain (エファモル society of Britain)) in part, heating mixing and After homogenizing, it is supplied in capsule filling machine, the gelatin covered by soft gum that every 1 intragranular capacity is 250mg is studied by conventional method Capsule preparation.This capsule preparations can be utilized as the dietary supplement of orally available picked-up, pharmaceuticals or animal feed.

Study example 2 (hard capsule)

By test portion 1 and test portion 3 (mixing ratio: 10/1), test portion 1 and test portion 4 and test portion 6 (mixing ratio: 10/3/1), test portion 1 And test portion 4 and test portion 7 (mixing ratio: 10/1/1), test portion 1 and test portion 4 and test portion 5 and test portion 7 (mixing ratio: in 10/2/1/1) Any one is supplied in capsule filling machine, studies, by conventional method, the gelatin that every 1 intragranular capacity is 200mg and coats hard capsule Preparation.This capsule preparations can be utilized as the dietary supplement of orally available picked-up, pharmaceuticals or animal feed.

Study example 3 (beverage)

The commercially available nourishing beverage of 100ml is separately added into: test portion 1 and test portion 3 (mixing ratio: 10/1), test portion 1 and test portion 7 (mixing ratio: 10/1), test portion 1 and thioctic acid (mixing ratio: 10/1) each 1000ml, be sufficiently mixed and study beverage.Even if by its Refrigerator preserves and also will not find within 6 months that outward appearance and local flavor are abnormal and unnatural.This product can be used as improving dry, bullet Property the skin condition of reduction, pachylosiies etc. and/or promote the beverage of U.S. flesh or potus and be utilized.

Industrial applicability

Contain collagen peptide and one or more groups selected from above-mentioned specific three kinds of improving blood flow agent Become to be used together thing as the U.S. flesh accelerator of the present invention of effective ingredient, due to by having its orally ingestible or administration Improve the drying of skin, elasticity reduces, pachylosiies and/or the effect promoting U.S. flesh, therefore, it is possible to diet product, pharmaceuticals, The field of non-pharmaceutical products, feedstuff etc. carries out effectively utilizes.

Claims

1. a kind of U.S. flesh accelerator it is characterised in that contain only collagen peptide and improving blood flow agent as effective ingredient, its In, described improving blood flow agent is from the group being made up of resveratrol class and the plant extract containing described resveratrol class Select one or more, or, described improving blood flow agent be from by resveratrol class and contain described resveratrol class The group that constitutes of plant extract in select one or more and constitute from Flos Camelliae Japonicae seed extract and thioctic acid class Group in select one or more.

2. U.S. according to claim 1 flesh accelerator is it is characterised in that described collagen peptide is collagen protein or gelatin Hydrolyzable thing and mean molecule quantity be 200～10000.

3. U.S.'s flesh accelerator according to claim 1 it is characterised in that described Flos Camelliae Japonicae seed extract be by water and/or Lower alcohol carries out the water composition obtained by extraction process to the defat dregs of rice of Camellia.

4. the U.S. flesh accelerator according to claim 1 or 3 is it is characterised in that described Flos Camelliae Japonicae seed extract is containing saponin The extract of class, described saponinss are containing by Tsubaki-saponin a1, Tsubaki-saponin a2, Tsubaki-saponin b1, Tsubaki-saponin b2, Flos Camelliae Japonicae One or more the saponinss selecting in the group of saponin c1 and Tsubaki-saponin c2 composition.

5. U.S. according to claim 1 flesh accelerator is it is characterised in that described thioctic acid class is from by thioctic acid, dihydro Thioctic acid, their salt, their carboxylate, their amide and their cyclodextrin clathrate or lipid coating group Become group in select one or more.

6. U.S. according to claim 1 flesh accelerator is it is characterised in that described thioctic acid class is from by thioctic acid, dihydro Thioctic acid, their salt, their carboxylate, their amide and their cyclodextrin clathrate or lipid coating group The outer surface of one or more the crystallization, powder and/or particle that select in the group becoming is coated and formed by lipid Material.

7. the U.S. flesh accelerator according to claim 5 or 6 is it is characterised in that described thioctic acid and/or described dihydro sulfur are pungent Acid is racemic modification.

8. U.S. according to claim 1 flesh accelerator is it is characterised in that described resveratrol class is containing from by white hellebore One or more the combination selected in the group of alcohol, ε-grape element and their isomer and/or glucoside composition Thing.

9. U.S.'s flesh accelerator according to claim 1 is it is characterised in that contain the plant extract of described resveratrol class Be the stem of plant by belonging to Vitaceae Vitis, climing, sprouting or flower be material obtained from raw material.

10. a kind of composition for oral administration of the U.S. flesh accelerator described in any one containing claim 1～9, wherein, described Improving blood flow agent is Flos Camelliae Japonicae seed extract and resveratrol class or the plant extract containing resveratrol class.

11. composition for oral administration according to claim 10 are it is characterised in that described composition for oral administration is diet Product.

A kind of 12. beauty methods, for reducing to the drying of skin, elasticity, the skin condition of pachylosiies improved and/or Promote U.S. flesh it is characterised in that the U.S. flesh accelerator described in orally ingestible claim 1～9 any one or claim Composition for oral administration described in 10～11 any one, wherein, described beauty method does not include the Therapeutic Method of dermatosis.