CN107050438A - Beautiful-skin-promoagent agent and use thereof - Google Patents

Abstract

The problem of the present invention is that providing a kind of skin condition to the drying, elastic reduction, pachylosis of skin etc. is improved and/or promoted the U.S. flesh accelerator of U.S. flesh, coordinates the U.S. flesh accelerator and formed and the beauty method for promoting the composition for oral administration of U.S. flesh and for improving skin condition and/or promoting U.S. flesh.There is provided as active ingredient containing collagen peptide and improving blood flow agent and U.S. flesh accelerator with thing, the method for coordinating composition for oral administration, the above-mentioned U.S. flesh accelerator of orally ingestible or above-mentioned composition formed by above-mentioned U.S. flesh accelerator, improving blood flow agent is particularly the one or more selected from the group being made up of camellia seed extract, lipoic acid class, resveratrol class and plant extracts containing resveratrol class.

Description

Beautiful-skin-promoagent agent and use thereof

Present patent application is that (international application no is PCT/JP2012/ to Application No. 201280020408.4 061191), the applying date is on April 26th, 2012, the application for a patent for invention of entitled " Beautiful-skin-promoagent agent and use thereof " Divisional application.

Technical field

The present invention relates to a kind of U.S. flesh accelerator, coordinate composition for oral administration and its utilization formed by the U.S. flesh accelerator Method.Wherein, U.S. flesh accelerator is characterised by that contain collagen peptide and improving blood flow agent forms as active ingredient, uses Improved and/or for forming more beautiful skin in the wrinkle of skin, the skin problem for moistening, compacting, relaxing etc..

Background technology

Skin is made up of epidermis, corium, hypodermis.Epidermis is made up of cuticula, stratum granulosum, spinous layer and basalis, greatly The cell containing keratinocyte, melanocyte etc. is measured, playing 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 or bullet produced by fiber sprout cell Property albumen etc. the extracellular components such as the mucopolysaccharide of protein, hyaluronic acid or chondroitin sulfate etc. occupied by, form matrix Structure and realize following effect：Support cell and skin histology, the moisture kept in space between cells, the lubricity for keeping skin and Flexibility, from from ultraviolet, dry environment, mechanical irritation or damage, microorganism infection etc. external factor protect skin Organize (non-patent literature 1).

But, increase or daily ultraviolet of the above-mentioned extracellular matrix components by the age are influenceed and are denatured, decomposed, and And decaying according to fiber sprout cell, its synthetic quantity also reduces.It is well known that the decomposition of above-mentioned extracellular matrix and synthetic quantity drop It is low, dry skin, pachylosis, elasticity or flexibility reduction can be caused, compact sense or gloss reduce, it is increase wrinkle, relaxation, dark The various skin problems of light grade.Therefore, skin is beautified in order to improve skin state and/or maintain to promote, it is desirable to make skin cell Activation, supplement further enhance it because of the composition of age increase or ultraviolet reduction.Particularly, collagen accounts for skin About the 70% of the dry weight of skin tissue, the viscoplasticity with skin is closely related.Also, hyaluronic acid is the guarantor to skin histology The wet material for having a significant impact, thus maintain, the collagen in enhancing skin histology and hyaluronic acid are vital.

In order to strengthen using collagen or hyaluronic acid as the composition in the skin histology of representative, or suppression skin is old Change, various composition is have studied so far, analyte (patent document 1), the N- acetyl Portugal of gelatin and/or collagen is currently suggested Osamine (patent document 2), sphingomyelin (patent document 3), Genkwanin (patent document 4), raspberry (patent document 5) etc..

But, physiological action that above material has to be presented in vivo, it is necessary to absorb in large quantities, even and if It is also and indefinite according to personal effect by taken long-term, and the situation of desired effects also can not be obtained, the energy from practicality The situation that validity is enough presented is less.Accordingly, it would be desirable to which developing a kind of can effectively facilitate the material or composition of above-mentioned U.S. flesh.

Here, improving blood flow agent refers to the improvement improved to the function that blood is transported in each tissue of organism Agent.Blood is carried out to distal tissues supply oxygen, nutritional ingredient, moisture, hormone etc., is carried immunocyte, discharge metabolin, is adjusted Body temperature etc. is saved, very important role is assume responsibility in the function of bio-tissue is maintained.It is well known that by improving blood flow, Artery sclerosis symptom, hypertension symptom, immunity degradation, alopecia symptom, fatigue, edema, shoulder acid, chilly, trick can be relaxed The symptom of numb, livid ring around eye or skin dimness etc..

As the material of blood flow is improved, proposition has such as ginkgo biloba p.e, safflower extract, intacellin, capsicum Extract, capsaicine, panax ginseng extractum, Japanese Herba Swertiae bimaculatae extract, pheophytin, vitamin e and its derivative (vitamin E acetate Deng), pantothenic acid and its salt (calcium salt, sodium salt etc.), glycyrrhizic acid or enoxolone and their salt (sodium salt, sylvite etc.), variegated leaf campanilla Extract, arginine and its derivative (arginine glutamic acid etc.), nicotinic acid and its derivative (methyl esters etc.), rosemary is set to extract Thing, Ginger P.E, salad oil, gingerol, zingerone, isoflavones, vitamin B₃, Turmeric P.E, the seed of grape, leaf, stem Deng extract, Extraction of rutin thing, fermentation rice germ extract, angelica extract, garlic extract, Chinese pepper extract etc.. But, research is not found suppresses the combination of composition to skin histology on these improving blood flow materials and above-mentioned skin ageing Or the report of influence caused by skin state.

Prior art literature

Patent document

Patent document 1：Japanese Unexamined Patent Publication 2004-123637 publications

Patent document 2：Japanese Unexamined Patent Publication 2001-48789 publications

Patent document 3：Japanese Unexamined Patent Publication 2005-281257 publications

Patent document 4：Japanese Unexamined Patent Publication 2004-137217 publications

Patent document 5：Japanese Unexamined Patent Publication 2003-137801 publications

Non-patent literature

Non-patent literature 1：Fu Bu roads are wide,《The science of skin nursing》, page 6~page 14, (strain) skirt China room, 1997 Issue within 25 days 2 months

The content of the invention

Technical problem

In view of related present situation, the present inventors are using the description below as problem, i.e. the U.S. flesh accelerator of exploitation to scaly dry skin, The skin state of elastic reduction, pachylosis etc. is improved and/or promoted U.S. flesh to be formed there is provided the U.S. flesh accelerator is coordinated The composition for oral administration for being used to promote U.S. flesh and for improving skin state and/or promoting the method for U.S. flesh.

Technical scheme

In order to solve above-mentioned problem, the present inventors are carried out repeatedly with keen determination to the relevance of various materials and U.S. flesh The result of discussion finds that the combination of collagen peptide and the material acted on improving blood flow unexpectedly produces remarkable result, especially It from camellia seed extract, lipoic acid class, resveratrol class and contains white black false hellebore in the material acted on improving blood flow At least one selected in the plant extracts of alcohols is used together especially effective with collagen peptide.Also, it is also found that it was possible to In the Orally administered composition that it is effectively used in diet product, feed, pharmaceuticals, non-pharmaceutical products etc., so as to complete the present invention.

That is, it is a feature of the present invention that containing improving blood flow agent and collagen peptide as active ingredient and forming U.S. flesh Accelerator.In the U.S. flesh accelerator, collagen peptide is preferably adding water by collagen, gelatin and collagen and gelatin The one or more selected in the group of analyte composition, above-mentioned hydrolyzable thing is preferably its molecular weight (mean molecule Amount, same as below) it is about 200~about 10000.Also, improving blood flow agent is particularly preferably from camellia seed extract, lipoic acid Selected in the group of class, resveratrol class and plant extracts composition containing resveratrol class it is at least one or two with On.

Above-mentioned camellia seed extract is containing the degreasing dregs of rice progress extraction process institute for passing through water and/or lower alcohol to camellia seed The extract of obtained water composition, is preferably the extract containing saponins, the saponins is especially preferably from Tsubaki-saponin (Camelliasaponin) A1, Tsubaki-saponin A2, Tsubaki-saponin B1, Camelliasaponin B2, Tsubaki-saponin C1 and Tsubaki-saponin The one or more selected in C2.

Also, lipoic acid class is preferably by lipoic acid (including racemic modification), its reduced form, their salt, their ester The one kind or two selected in the group of compound, their acid amides and their cyclodextrin inclusion compound or lipid coating composition Plant the compound of the above.

Further, resveratrol class be preferably from the polymer of the monomer by resveratrol or ε-grape element etc. and it Isomers and/or glucoside composition group in the one or more selected, its more preferred form is Vitaceae The extract of plant, polygonaceae plant or legume.

Other of the present invention are characterised by that the material preferably as the above-mentioned U.S. flesh accelerator of orally ingestible or administration is oral With composition, and the composition for oral administration is diet product.Other are further characterized in that, orally ingestible collagen peptide and improving blood flow Agent and improved and/or promoted the side of U.S. flesh for the skin state to the drying of skin, elastic reduction, pachylosis etc. 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 formed, and the stability of quality etc. is excellent It is different, act on Skin Cell to significantly improve its propagation, promote the generation of the skin components of collagen hyaluronic acid etc., it is extensive Composition in multiple, maintenance, enhancing skin histology.By by improving blood flow agent especially from camellia seed extract, lipoic acid class, white lamb's-quarters Select at least one to be used together with collagen peptide in reed alcohols, make its effect enhancing.Thus, following effect is produced, i.e. right The drying of skin, coarse, elastic or flexibility reduction, the reduction of gloss, the increasing of wrinkle, the increasing of relaxation, dim increasing Plus the skin problem waited is prevented and/or improved, and further promote U.S. flesh.Promoted by the above-mentioned U.S. flesh of orally ingestible or administration Enter agent and significantly find related effect.Therefore, above-mentioned U.S. flesh accelerator is particularly in diet product, feed, pharmaceuticals, non-medicine In the field of articles for use etc., directly it can be carried out with the form of above-mentioned preparation or with the form for being combined into conventional various products effectively Utilize.Also, the present invention provides a kind of orally ingestible collagen peptide and improving blood flow agent and for the drying to skin, bullet The skin state of property reduction, pachylosis etc. is improved and/or promoted the beauty method of U.S. flesh.

Embodiment

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

The collagen peptide used in the U.S. flesh accelerator of the present invention is, by the domestic animals of ox, pig, chicken, turkey, ostrich etc. Skin, bone, cartilage or tendon etc. and red coat, salmon, shark, cod, Tilapia mossambica, Nile perch, carp, flat Rockfish fishes, tuna, Skin, bone, cartilage or squama of the fish of catfish, eel etc. etc. are as raw material, glue obtained to being handled by common method The gelatin that former albumen or make is obtained after the collagen thermal denaturation, the peptide of hydrolyzable and gained is carried out by acid, alkali or enzyme. This, described collagen peptide includes collagen peptide and the extract containing collagen peptide in the present invention, and can be any Use above-mentioned substance.It is relatively simple using commercially available product to collagen peptide.

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

Also, according to the improving blood flow agent of the U.S. flesh accelerator of the present invention, extract, the lipoic acid of camellia seed can be used Class, resveratrol class, the plant extracts containing resveratrol class, ginkgo biloba p.e, safflower extract, intacellin, Pepper extract, capsaicine, panax ginseng extractum, Japanese Herba Swertiae bimaculatae extract, pheophytin, vitamin e and its derivative (acetic vitamin E etc.), pantothenic acid and its salt (calcium salt, sodium salt etc.), glycyrrhizic acid or enoxolone and their salt (sodium salt, sylvite etc.), variegated leaf campanilla Extract, arginine and its derivative (arginine glutamic acid etc.), nicotinic acid and its derivative (methyl esters etc.), rosemary is set to extract Thing, Ginger P.E, salad oil, gingerol, zingerone, isoflavones, vitamin B₃, Turmeric P.E, the seed of grape, leaf, stem Deng extract, Extraction of rutin thing, fermentation rice germ extract, angelica extract, garlic extract, Chinese pepper extract etc., And above-mentioned example is not limited to, one or more kinds of materials acted on improving blood flow can be used.

In connection with this, the inventors of the present invention with collagen peptide and use to by that can play more potent Result that the improving blood flow agent of U.S. flesh facilitation effect is further studied in detail finds, the extract of camellia seed, lipoic acid class, And resveratrol class or plant extracts containing resveratrol class it is extremely effective.That is, currently preferred U.S. flesh accelerator The characteristics of be, collagen peptide is contained as active ingredient and from by camellia seed extract, lipoic acid class, resveratrol class And containing resveratrol class plant extracts composition group in select one or more and formed.

The camellia seed extract for being related to the present invention is carried out described in detail below.Camellia, which refers to, belongs to Theaceae (Theaceae) The camellia (camellia japonica) of the camellia system of Camellia (Camellia), can enumerate as example：Shallow lake overgrown with wild plants Chinese toon (C.japonica var.japonica), snow mountain tea (C.japonica subsp.rusticana), Chinese pear-leaved crabapple Chinese toon (C.japonica var.macrocarpa), phoenix camellia (C.japonica subsp.hozanensis), Hong Kong camellia (C.hongkongenesis), Camellia reticulata (C.reticulata), Nujiang camellia (C.saluenensis), southwestern camellia class (C.pitardii var.pitardii) and Camellia reticulata class (C.pitardii var.yunnanica), Camellia nitidissima (C.nitidissima), wild camellia (of the same race with shallow lake overgrown with wild plants Chinese toon), camellia (of the same race with shallow lake overgrown with wild plants Chinese toon), the long island mountain tea in room are (same with Chinese pear-leaved crabapple Chinese toon Kind) etc..These camellias suitably using Japanese Science Society, the Korea peninsula, Shandong Province of China peninsula etc. place naturally growth or cultivation and Into camellia.

In order to manufacture the camellia seed extract according to the present invention, it is preferable that by the fruit of above-mentioned camellia and/or seed supply The liquefaction of the hydrophobic organic solvent or liquefied carbon dioxide of hexane or heptane etc., liquefied propane etc. is handled and used to squeezing In supercritical extract processing of gas etc., then the degreasing thing as residue that oil content is separated will be extracted by common method (the hereinafter referred to as degreasing dregs of rice) are used as raw material.Here, during the fruit and/or seed of camellia can be precocious fruit and ripening fruits Any one, can also use their seed, but if using ripening fruits or its seed, then degreasing 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 into The material that the seed obtained in ripe fruit is dried at 1~2 week or so, by sunshine etc..

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

When extracting the degreasing dregs of rice, the said extracted solvent of about 1~about 30 times of quality is added for the degreasing dregs of rice of 1 mass parts, At ambient pressure or under the pressurization of about 1~about 5 atmospheric pressure, at a temperature of normal temperature~about 120 DEG C, about 10 minutes~about 3 hours, As needed stirring and after being mixed, cooled and filtered under normal temperature, by being dried under reduced pressure, being spray-dried, freeze-dried etc. Appropriate method is concentrated and dried to filtrate.Appropriate pulverization process can also be carried out to the dried object.It can so obtain The faint yellow solid to crocus of the water soluble ingredient contained in camellia seeds as the present invention.Said extracted method passes through Extraction residue after extraction process is repeated identical extraction process, or in the pressurization of about 1~about 3 atmospheric pressure Under, and extraction process is carried out at about 100~about 130 DEG C, the amount to obtain of the water soluble ingredient of the present invention can be increased, also, Said extracted thing is further carried out solvent point carry, the absorption by being filled with ion exchange resin, silica gel, activated alumina etc. The classification of the tubing string of agent, concentration essence can be carried out to active component by the well-known means that liquid chromatography is separated etc. System.The water soluble ingredient contains saponin(e, tannic acid etc..

As the saponin(e contained in above-mentioned water soluble ingredient, can enumerate as：As 3 β-[2-O- β-D- galactopyranosyls glycosyl- 3-O- (2-O- β-D- glucopyranosyl-α-L- arabopyranoses base)-beta d glucopyranosiduronic acid epoxide] olive- 12- alkene -16 α, 22 α, 28- triols 22- [(Z) -2- methyl-2-butenes 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 ー Le 22- [(Z) -2- メ チ Le -2- Block テ ノ ア ー ト]) Tsubaki-saponin (Camelliasaponin) A1, as 3 β-[2-O- β - D- galactopyranosyl glycosyls -3-O- (2-O- β-D- glucopyranosyl-α-L- arabopyranoses base)-β-D- glucopyra alditols Acyloxy] olive -12- alkene -16 α, 22 α, 28- triols 22- [(E) -2- methyl-2-butenes 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 ー Le 22- [(E) -2- メ チ Le -2- Block テ ノ ア ー ト]) Tsubaki-saponin (Camelliasaponin) A2, conduct 3 β-[2-O- β-D- galactopyranosyl glycosyls -3-O- (2-O- β-D- glucopyranosyl-α-L- arabopyranoses base)-β-D- pyrroles Glucopyranoside aldehydic acid epoxide]-16 α, the α of 28- dihydroxies-22-[[(Z)-2- methyl-2-butenes 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 ー Le) Tsubaki-saponin (Camelliasaponin) B1, be used as 3 β-[2-O- β-D- galactopyranosyl glycosyl -3-O- (2- O- β-D- glucopyranosyl-α-L- arabopyranoses base)-beta d glucopyranosiduronic acid epoxide] -16 α, 28- dihydroxies -22 α-[[(E) -2- methyl-2-butenes 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 ー Le) and Tsubaki-saponin (Camelliasaponin) B2, as 3 β-[2-O- β-D- galactopyranosyl glycosyls -3-O- (2-O- β-D- glucopyranosyls-α - L- arabopyranoses base)-beta d glucopyranosiduronic acid epoxide] olive -12- alkene -16 α, 22 α, 23,28- tetrols 22- [(Z) -2- methyl-2-butenes 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] -16 テ ト ラ オ ー Le 22- [(Z) -2- メ チ Le -2- Block of α, 22 α, 23,28- of オ レ ア Na -12- エ Application テ ノ ア ー ト]) Tsubaki-saponin (Camelliasaponin) C1 and be used as 3 β-[2-O- β-D- galactopyranosyl glycosyls -3- O- (2-O- β-D- glucopyranosyl-α-L- arabopyranoses base)-beta d glucopyranosiduronic acid epoxide] olive -12- Alkene -16 α, 22 α, 23,28- tetrols 22- [(E) -2- methyl-2-butenes 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] -16 テ ト ラ オ ー Le of α, 22 α, 23,28- of オ レ ア Na -12- エ Application 22- [(E) -2- メ チ Le -2- Block テ ノ ア ー ト]) Tsubaki-saponin (Camelliasaponin) C2 etc..In camellia Distinguishingly contain these saponinses.

Also, it is originated according to the lipoic acid class of the present invention and species is not particularly limited, can be to ox or pig The natural extract of the internal organs such as liver, or to such as ethene and adipate ester for the synthetic of initiation material, with public affairs The material that the method known is taken, manufactured.Here, lipoic acid is due to asymmetric carbon atom, therefore there is optical property Different mirror image isomers (R- enantiomers and S- enantiomers), but can be that any of the above is a kind of according to the lipoic acid of the present invention Single enantiomer or above-mentioned enantiomer can also be racemic modification (racemic mixture with the mixture of arbitrary proportion Or racemic compound) (RS- lipoic acids).When implementing in the industrial production, using it is cheap and be readily obtained it is commercially available Racemic modification is relatively simple.Due to when using racemic modification when, make the tendency that the effect desired by the present invention preferably embodies compared with Greatly, therefore racemic modification is preferably used.

The lipoic acid class used in the U.S. flesh accelerator of the present invention can suitably utilize each in addition to above-mentioned lipoic acid Kind of derivative, be preferably by lipoic acid, its reduced form, their salt, their carboxylate, their acid amides and they The material of one or more is selected in the group of cyclodextrin inclusion compound composition.

As the specific example of the reduced form of lipoic acid, can enumerate as：Dihydrolipoic acid (ジ ヒ De ロ チ オ Network ト acid), Dihydrolipoic acid (ジ ヒ De ロ リ Port acid), 6,8- dimercapto octanoic acids, RS- dihydrolipoic acids etc..

As salt can enumerate as：LA, S- lipoic acids, RS- lipoic acids, R- dihydrolipoic acids, S- dihydrolipoic acids, Sylvite, sodium salt, calcium salt, magnesium salts of RS- dihydrolipoic acids etc. etc..

As ester can enumerate as：Make LA, S- lipoic acids, RS- lipoic acids, R- dihydrolipoic acids, S- dihydro sulphur pungent Acid, RS- dihydrolipoic acids etc. and polyalcohol (ethylene glycol, propane diols, butanediol, neopentyl glycol, glycerine, erythrol, polyglycereol Deng monomer or polymer) formed partial esterification product complete esterification products or with glyceride type (monoglyceride, glycerine Diester, triglycerides) or with carbon number for 10~22 higher alcohols (Decanol, laruyl alcohol, myristyl alcohol, cetanol, N-octadecane alcohol, isooctadecane alcohol, behenyl alcohols etc.) monoesters etc. that is formed.

As acid amides can enumerate as：Make LA, S- lipoic acids, RS- lipoic acids, R- dihydrolipoic acids, S- dihydro sulphur The acid amides of octanoic acid, RS- dihydrolipoic acids etc..

As cyclodextrin inclusion compound can enumerate as：α-, β-, γ-or δ-cyclodextrin and above-mentioned lipoic acid or its derivative The inclusion compound that thing is formed.

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

In the present invention, also included as lipoic acid class：From by above-mentioned lipoic acid, its reduced form, their salt, they Carboxylate, their acid amides and they cyclodextrin inclusion compound composition group in select one or more crystallizations, The outer surface of powder and/or particle by lipid coat formed by material, due to the form to the thermal metamorphism of lipoic acid class (point Solution, polymerization, discoloration etc.), moisture absorption or oxidative deformation suppressed, therefore more preferred form from practicality.

The lipid of crystallization, powder and/or the particle external surface of above-mentioned lipoic acid class is coated, can utilize the present invention Industrial field in allow the material that uses, 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 Deng being utilized alone or in combination.In material listed above, if it is considered that the operability of cladding and the physical property of coating are (stable Property, curability, 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 the situation of solid-state being unable to maintain that when it is used, block is formed or damages flowing Property situation occur., whereas if greater than about 70 DEG C, when manufacturing the inhibitor or composition according to the present invention, at heating The influence of reason or mechanical energy, has the danger that lipoic acid class itself degenerates.

As the specific example of such lipid, can enumerate as：Soybean oil, rapeseed oil, corn oil, Semen Benincasae oil, cottonseed Oil, wheat-germ oil, rice bran oil, sesame oil, olive oil, safflower oil, palm oil, palm kernel oil, coconut oil, linseed oil, peanut The animal system grease of department of botany's grease, butter, lard, the fish oil of oil etc. etc., above grease is applied with point carry, it is ester exchange, de- The processing grease of one or more of the processing of color, deodorization etc., each of partially or completely hydrotreating is carried out to above grease Plant saturated fatty acid (acetic acid, butyric acid, caproic acid, octanoic acid, capric acid, laurate, nutmeg that fixed oil, carbon number are 2~22 Acid, pentadecanoic acid, palmitic acid, stearic acid, 12- hydroxy stearic acids, isostearic acid, arachidic acid, behenic acid etc.) or unsaturated fat Sour (palmitoleic acid, oleic acid, linoleic acid, alpha-linolenic acid gamma-Linolenic acid, castor oil acid, arachic acid, eicosapentaenoic acid (EPA), erucic acid, docosahexaenoic acid (DHA) etc.), salt (sodium salt, sylvite, calcium salt, the magnesium salts of any of the above aliphatic acid Deng), with monohydric alcohol (methanol, ethanol, propyl alcohol, butanol etc.) formation esters, with polyalcohol (ethylene glycol, propane diols, butanediol, The polymer of the non-monomer of neopentyl glycol, glycerine, erythrol, polyglycereol etc.) formed partial esterification product or completely esterification Product or glyceride type (monoglyceride, diglyceride, triglycerides) or with carbon number for 10~22 higher alcohols (just Decyl alcohol, laruyl alcohol, myristyl alcohol, cetanol, n-octadecane alcohol, isooctadecane alcohol, behenyl alcohols etc.), wax class (Zong Beam-at-the-eaves waxes, rice wax The wax from plant of (rice bran wax), candelila wax etc., beeswax, spermaceti, shellac wax etc. derive from the wax of animal, paraffin, micro- Brilliant wax etc. derives from the wax of oil, 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., ergosterol, their derivative from mushroom), sugared lipid (monosaccharide groups diglyceride (モ ノ グ Le U シ Le ジ グ リ セ リ De), monogalactosyl diglyceride, disaccharide base monoglyceride (ジ グ Le U シ Le モ ノ グ リ セ リ De), Double galactolipin monoglycerides (ジ ガ ラ Network ト シ Le モ ノ グ リ セ リ De), monosaccharide groups diglyceride, digalactosyl diglyceride, Sucrose fatty ester etc.).It should be noted that the present invention is not the invention limited by above-mentioned example.

Any one or two or more mixtures 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, also, fusing point adjustment from cladding lipid, coating film From the viewpoint of reinforcing etc., be more preferably them with from fatty acid, higher alcohols, steroid, sugared lipid or Phospholipids The form that the one or more kinds of materials selected in class are combined.

Using known method the outer surface of crystallization, powder and/or the particle of lipoic acid class can be made to be coated by lipid. I.e., it is possible to be following methods：Using ball mill, scouring type mixer (bulk material mixer), V-Mixer, high-speed mixer, High speed paddle mixer, heating melting mixing machine, ultrasonic wave overly moist liquid adding type mixer, barrel mixer, pressurization extruder Deng making crystallization, powder and/or the particle of lipoic acid class uniformly mix, cool down with the lipid of heating melting and make after it solidifies The method crushed；To carry out the liquefied lipid after suitable heating spraying or drippage and to the lipoic acid of above-mentioned form The method that class is coated；The lipoic acid class of above-mentioned form is carried out into high-speed stirred with the lipid of particle shape mixes it, leads to Crossing makes both contact or collide so that the lipid of particle shape is uniformly attached to crystallization, powder and/or the particle of lipoic acid class Integral surface and the method coated.In the present invention, in the above method be preferably, by the crystallization of lipoic acid class, powder and/ Or particle carries out high-speed stirred with particle shape lipid more than above-mentioned specific fusing point and mixes it, by making both contact or touch Hit so that the lipid of particle shape is evenly coated at the method on the integral surface of the lipoic acid class of above-mentioned form.

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

Here, the coating of the lipid by above-mentioned lipoic acid class, with being applied to beverage etc. with the presence or absence of by it Situation in water system composition is unrelated, still more preferably to make its outer surface coat formed form by close substances in aquatic system Material.Here, described close substances in aquatic system refers to, the further outer surface of coating of the cladding from lipid, can be formed and Aqueous substance has the material for being wrapped by film of compatibility, can enumerate as a specific example as：Polysaccharide (xanthans, cluster bean Glue, tamarind gum, plantasan etc.), starch and chemical starch, yeast cell wall component, glucose, mannosan, shellac, sea Mosanom, gelatin, carragheen, amylopectin, carboxymethyl cellulose, soybean protein, lactalbumin, zein etc..It is more excellent Elect as from polysaccharide, starch, yeast cell wall component, shellac, gelatin, soybean protein, zein and mannosan composition Group in select one or more kinds of；The group more preferably constituted from yeast cell wall component, shellac and gelatin Middle selection is one or more kinds of.

, can be using the method for coating according to above-mentioned lipid when being coated by related close substances in aquatic system Method.That is, above-mentioned close substances in aquatic system is suitably dissolved in water, ethanol, other solvents and form liquid material, be attached to it pre- First coated by lipid lipoic acid class outer surface, dry after can form the coating film of close substances in aquatic system.Related cladding Thing formation is being used in diet product, feed, cosmetics, doctor using close substances in aquatic system as outermost dual cladding structure In the case of medicine etc., the compatibility with aqueous raw material or composition is improved, can be easily low by them and water-soluble Lipoic acid class is formulated as homogeneous composition.

The lipid from lipoic acid class as described above coating and make the coating further by hydrophilic system In the dual cladding thing of material cladding, by the way that it coexists in them and with following substances, it can further suppress sulphur The heat of sad class and/or denaturation or the variation of oxidation, obtain the coating of the lipoic acid class of excellent in stability, therefore in this hair The lipoic acid class of more preferred relevant form in bright, above-mentioned substance is：From HCA pericarp, red rattletop rhizome, Guava Leaf and Their extract (passes through water and/or extract, its point of hydrophilic organic solvent (low-grade monobasic alcohol such as ethanol, acetone etc.) Level thing or solvent fraction leach-s/tive or refined thing etc.), select one or more kinds of in the group of carnitine composition, it is more preferably red The extract and carnitine of rattletop rhizome, most preferably carnitine.

The coating of foregoing lipoic acid class is set to contain above-mentioned and be in following form with the form of raw material The combination of any one or these forms, i.e.,：(i) make lipid be coated on the crystallization of lipoic acid class, powder and/ Or mixed in the coating on particle it is above-mentioned and with raw material, (ii) by the crystallization of lipoic acid class, powder and/or particle with it is above-mentioned And carried out coating lipid, (iii) bag on the crystallization of lipoic acid class, powder and/or particle on mixed material with raw material Be covered with state and do not disperseed with a part for raw material and make its dissolve lipid, (iv) the crystallization of lipoic acid class, powder and/ Or attachment is coated on the coating of lipid on particle and with lysate, dispersion liquid or the emulsification of raw material and above-mentioned close substances in aquatic system Liquid and drying and coated.In the present invention, (i) and (iv) form reach the effect of the present invention, manufacture simplicity, coating Use good operability, still (i) and (iii) form be easy to embody more potent desired effect.

In related form, coated on the crystallization of lipoic acid class, powder and/or particle lipid or lipid and The coating of close substances in aquatic system with it is above-mentioned and with the mixed proportion of raw material be：Relative to the mass parts of coating 1, it is above-mentioned and 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, Can not approve can obtain the raising of desired effect by mixing and with raw material；In the case of more than about 10 mass parts, In above-mentioned coating, reduced especially with the lipoic acid content in its composition, and then cooperation can be limited and contain lipoic acid Lipoic acid content in the various products of based composition, the desired effect of lipoic acid itself can not be expected in the product stage Really.

Can be known organic chemistry according to the source of the resveratrol class of the present invention or species and unspecific material Method or be the material taken, manufactured using microorganism or yeast etc., it is preferred that for from Vitaceae, polygonaceae or beans The material that the position of pericarp, stem, leaf, climing, sprouting, seed, flower, the fruit of the plant of section etc. 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 can for example enumerate 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, pellet soul, Ta Mingna, cut piece more, it is the red, Mo Niyepinuo of red phenanthrene, general Sa, Furmint, blue brier grape tooth people, Moschus, Ma Er Visas, 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 grape, peace rue queen consort, Vidal Blanc, Ju Feng, Momotaro grape, Su Weiweng In vain (セ イ ヴ ァ Le Block ラ Application), Di Lawa, Niagara, new Moschus, Hei Bake, Bai Bake, Pi Aonai, bud rose, Rattan is harvested, Rome ruby, Jia Fei roads, the chi of Jia state three etc..They can be suitably utilized in Chile, Japan, Italy, France etc. The grape that ground grows or cultivated naturally, can be extracted from each position of the kind of above-mentioned example, more preferably from stem, climing, sprouting Or spend middle extraction.

It can be manufactured according to the resveratrol class of the present invention by any means, but can be any one in following substances Kind：That is, be dried, chop up using the stem of grape of above-mentioned example, climing, sprouting or flower itself or by them, pulverization process Material, and Extraction solvent during it is impregnated into the scheduled time in a solvent or makes it and is heated to reflux contacts and extracted Liquid, will from the extract solution remove solvent extract, to the extract carry out using silica gel, magnesium silicate, ion exchange resin, The refined thing for the refinement treatment that the column chromatography or solvent of the adsorbent of activated alumina, cellulose, activated carbon etc. point are carried etc. and By these materials by method powdereds such as freeze-dried, spray drying.In the case of being used in food applications, from convenience From the viewpoint of manufacturing cost, be preferably, the position of above-mentioned plant is dried and suitably crushing after powder, by water Or hydrophilic organic solvent in small, broken bits of the dried object or powder are extracted after extract.Also, it is being used in doctor In the case of pharmaceutical product use, the preferably refined thing of said extracted liquid, extract or high-purity.

As hydrophilic organic solvent can enumerate as：The low-grade monobasic alcohol class of methanol, ethanol, normal propyl alcohol, isopropanol etc., third The polyalcohols of glycol, 1,3-BDO, glycerine etc., acetone, methyl ethyl ketone, ether, petroleum ether, ethyl acetate and it Hydrate or mixture.The extract for producing the effect desired by the present invention is being efficiently obtained, is being preferably by second Alcohol, acetone, ethyl acetate and their hydrate are used as extraction solvent.To the moisture of hydrate, for example, in ethanol In the case of, it is about 1~about 99 mass %, even more preferably about below 50 mass %；It is about 1~about 50 in the case of acetone Quality %, even more preferably about 10~about 30 mass %；It is about 80~about 99 mass %, more preferably in the case of ethyl acetate It is about 85~about 95 mass %.If departing from above range, the effect desired by the present invention can be reduced or the production of extract is reduced Amount.

According to the resveratrol class of the present invention using following compound as object, i.e. the trans-resveratrol (list of resveratrol Body) or ε-grape element (dimer), the polymer and their isomers and/or glucoside of going back age polyphenol (tripolymer) etc. Deng stilbene compound.Here, from the situation of the extract obtained by above-mentioned plant be using above-mentioned stilbene compound as main Active component, have comprising Quercetin, Ellagitannins, ellagic acid, mineral substance (such as potassium, calcium, phosphorus, magnesium), vitamin class situation.

In the U.S. flesh accelerator of the present invention, with collagen peptide and the content of improving blood flow agent be U.S. flesh promotion Agent all about 0.01~about 50 mass %, preferably from about 0.1~about 20 mass %, more preferably about 0.5~about 10 matter Measure %.If below about 0.01 mass %, and the effect caused by is small, conversely, the use more than about 50 mass % can not yet Expect preferably desired effect.It should be noted that improving blood flow agent can use above-mentioned public affairs alone or in combination and arbitrarily The material or extract known, it is preferred that from camellia seed extract, lipoic acid class, resveratrol class and to contain resveratrol The one or more selected in the plant extracts of class, more preferably comprising all above-mentioned substances.By camellia Among seed extract, lipoic acid class, resveratrol class and plant extracts containing resveratrol class it is two or more together Ratio (quality criteria) in the case of use is substantially：Camellia seed extract/lipoic acid class is 20/80~30/70, more excellent Elect 60/40~40/60 as；Camellia seed extract/resveratrol class is 99/1~30/70, more preferably 80/20~50/50； Lipoic acid class/resveratrol class is 99/1~30/70, more preferably 80/20~50/50；Also, to camellia seed extract/ Lipoic acid class/resveratrol class, the ratio of respective improving blood flow agent is more than the about 1 mass % of the total amount of U.S. flesh accelerator, more Plus be preferably to contain more than about 10 mass %.It should be noted that in the case of the plant extracts containing resveratrol class, It is contemplated that the content of resveratrol class in the extract and set.

Above-mentioned U.S. flesh accelerator with collagen peptide and improving blood flow agent (particularly from camellia seed extract, lipoic acid class, The one or more selected in resveratrol class and the plant extracts for containing resveratrol class) and use thing conduct Active ingredient, can directly be used, i.e. form the powdered, solid-like being only made up of above-mentioned active ingredient, pasty state or liquid Form, in the purposes for being used in diet product, pharmaceuticals, non-pharmaceutical products, feed etc..

The U.S. flesh accelerator of the present invention, can also suitably and use can utilize known in its such use add Thing, makes it contain and be utilized as composition for oral administration by conventional method.Here, known additive can be in order to Orally ingestible and usually used material, for example, excipient, bonding agent, disintegrant, mixed lubrication prescription, wetting agent, fluidisation can be used Agent, preservative agent, surfactant, stabilizer, diluent, lytic agent, tonicity agent, bactericide, preservative, flavouring, flavoring agent, The additive of colouring agent, spices etc..Further, the material described in above-mentioned prior art literature is not limited to, also may be used To be used in combination with the principal component or the raw material containing the composition that are acted on U.S. flesh and/or improving blood flow is acted on.U.S. of the present invention Flesh accelerator is also used as the cooperation original of diet product, pharmaceuticals, non-pharmaceutical products, feed, the various products of other industrial fields A part for material and used.It is particularly preferred that being used as the product for beauty etc..

In the case of using U.S. flesh accelerator and the known additive of the present invention and with and as composition for oral administration 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 the content to the above-mentioned active ingredient in related composition for oral administration provides consistent, But substantially 0.1~100 mass % or so, more preferably about 10~about 100 mass % or so.If above-mentioned content is below about 0.1 mass %, will be unable to accreditation desired effect of the 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 composition for oral administration of the invention in this case or administration amount is：With Based on the above-mentioned active ingredient contained in the agent, the daily about 100mg~about 100000mg of adult (body weight 50kg) is preferably About 500mg~about 10000mg, more preferably about 1000mg~about 5000mg.

The present invention U.S. flesh accelerator can as diet product, pharmaceuticals, non-pharmaceutical products, feed etc. known production A part for the cooperation raw material of product and utilized.Practical product is described below, but the present invention is not by this Any limitation of example.

As the specific example of diet product, can enumerate as：The beverage class of vegetable juice, fruit drink, cold drink, tea etc.； The snack categories of cake ready mix product, bread, cake, chocolate, candy, chewing gum, chewing gum etc.；Miso, soy sauce, sauce, egg The flavoring of yellow bean sauce, barbecue or flour juice etc.；The noodles of instant noodles, Noodle, buckwheat, pasta etc.；Ham or sausage etc. Poultry meat the flesh of fish processed food；The powdered of milk, Yoghourt, cream, butter, taste product or cheese etc., solid-like or liquid Dairy products；Seasoned food, hamburger, Deep-fried meatballs, the seafood delights being sprinkling upon on rice are cooked, jam, jelly, pudding, salad dressing, plant Property the various general processed foods that drench etc. of cream, Mai Qi, in addition also powdered, graininess, pill shape, tablet shape, soft Capsule shape, ebonite cryptomere, pasty state or liquid dietary supplement, specific health treatment, functional food, healthy food, Treatment food of high density liquid food or aphetite disorder food etc..

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

To the pharmaceuticals and non-pharmaceutical products of the U.S. flesh accelerator using the present invention, the technology of the present invention thought can not violated In the range of the known excipient or additive that pharmaceutically allow are added in above-mentioned oral U.S. flesh accelerator, pass through general side Method is processed and the preparation of piece agent, capsule, granule, pulvis, liquor etc..By oral suitable for prevention or treatment Dry, elastic reduction, pachylosis etc..It should be noted that the U.S. of the invention contained in these pharmaceuticals and non-pharmaceutical products Situation of the content or intake of flesh accelerator according to above-mentioned composition for oral administration.

Also, when making the U.S. flesh accelerator of the present invention suitable for 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 for the U.S. flesh accelerator of the invention contained in these feeds Or intake is roughly the same with the situation of above-mentioned composition for oral administration.

Embodiment

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

Production Example 1 (collagen peptide (1))

Added in the skin 1kg of the body of catfish and bone is eliminated under 5L water, normal pressure, be heated to after 85 DEG C appropriate stirring 1 Individual hour and extract gelatin.Gelatin solution is cooled to 50 DEG C, protein decomposition enzyme is added, 2 hour enzyme reactions are carried out.So Afterwards, inactivate enzyme, separating filtrate after filtering.The lower concentration filtrate of decompression, carries out freeze-dried and crushes, obtain 192g collagens Peptide (sample 1).HPLC analyses are carried out to the collagen peptide by conventional method, mean molecule quantity is about 1000.

Production Example 2 (collagen peptide (2))

It is net with massive laundering after being handled by 0.1N hydrochloric acid the squama of Tilapia mossambica, dry its sunshine.In drying Squama 1kg in add 8L water, under normal pressure, be heated to after 85 DEG C suitably stir 1 hour and extract gelatin.Gelatin solution is cooled down To 50 DEG C, protein decomposition enzyme is added, 1 hour enzyme reaction is carried out.Then, inactivate enzyme, separating filtrate after filtering.Under decompression Filtrate is concentrated, carries out freeze-dried and crushes, 711g collagen peptides (sample 2) are obtained.By conventional method to the collagen egg White peptide carries out HPLC analyses, and mean molecule quantity is about 5000.

Production Example 3 (camellia seed extract (1))

The dry seed that the shallow lake overgrown with wild plants Chinese toon on her Dou great islands will be originated in is carried out after coarse crushing boiling, and progress, which is squeezed, has been separated squeezing The squeezing dregs of rice of oil.Added in degreasing thing 1kg under 3L water, normal pressure, be heated to after 85 DEG C suitably stir after 1 hour, cooled down To room temperature, separating filtrate after filtering.Add after 1L water and carry out after identical heating, stirring, cooling again in the filtering residue, Filtered and take filtrate.Will two kinds of filtrates merge after be concentrated under reduced pressure, freeze-dried and crushing, obtain by water solubility into Powdered camellia seed extract (sample 3) 170g being grouped.HPLC analyses are carried out to the extract by conventional method, should Extract contains 7.5% Camelliasaponin B2,5.8% Tsubaki-saponin C2, a kind of 2.4% Kaempferol as flavonoids.

Production Example 4 (camellia seed extract (2))

2L hydrous ethanols (moisture content 35%) are added in progress and degreasing thing 1kg obtained from the same treatment of Production Example 3, It is heated to reflux at 80 DEG C after 1 hour, is cooled to separating filtrate after room temperature, filtering.2L is added again in the filtering residue Hydrous ethanol (moisture content 35%) is carried out after identical heating, cooling afterwards, is filtered and takes filtrate.Two kinds of filtrates are merged Concentrated under reduced pressure afterwards, after freeze-dried and crushing, obtain powder (sample 4) 12.1g of containing water-soluble composition.To the powder End carries out the result after being analyzed with the identical HPLC of Production Example 3：Containing 8.3% Camelliasaponin B2,5.9% Tsubaki-saponin C2, A kind of 2.6% Kaempferol as flavonoids.

Production Example 5 (the lipid coating of lipoic acid)

In lipoic acid (German Lai Yu companies (the De イ Star ア ルツケム societies) production, commodity of 330g crystalline powder Name：ALIPURE (registration mark), racemic modification) in add heating melting 200g hydrogenated rapeseed oils (river grind fine chemistry strain Formula commercial firm (grinding Off ァ イ Application ケ ミ カ Le (strain) in river) produces, fusing point：67 DEG C, sheet), it is sufficiently mixed and makes after it is uniformly dispersed, Solidification is allowed to cool at room temperature.Then, the solidfied material is crushed by homogenizer, passes through 100 mesh (taylor criteria net It is eye, same as below) sieved after to obtain particle diameter be less than 150 μm of lipoic acid lipid coating (sample 5).

Production Example 6 (cyclodextrin inclusion compound of lipoic acid)

Make lipoic acid (German Lai Yu companies (the De イ Star ア ルツケム societies) production, commodity of 100g crystalline powder Name：ALIPURE (registration mark), racemic modification) dissolved in 50% ethanol 500mL, add 800g alpha-cyclodextrin (Germany Wacker Chemical Co., Ltd (De イ Star ワ ッ カ ー ヘ ミ ー societies) produces, trade name：CAVAMAX (registration mark), (R) W6), suitably After stirring, make its concentration, spray drying, obtain lipoic acid cyclodextrin inclusion compound (sample 6).

Production Example 7 (resveratrol extract)

The sunshine dried object 500g of the stem of grape (Cabernet Sauvignon) is carried out after refluxing extraction by 2L 70% ethanol solution, Filtered and separating filtrate.70% ethanol for adding 1L again in the filtering residue carries out refluxing extraction, is filtered And separating filtrate.Concentrated under reduced pressure after two kinds of filtrates are merged, be spray-dried, obtained after adding dextrin wherein 24g resveratrol extracts (sample 7).It is by the result that the powder is carried out after HPLC analyses by conventional method：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) of participation experiment as described below will be obtained agreeing to It is grouped according to 5 one group, measuring of blood flow experiment is carried out according to double blind check method.First, subject is made to enter control temperature Spend for 24 ± 2 DEG C, the constant temperature and humidity room that humidity is 50 ± 10%, peace and quiet wait 10 minutes.Afterwards, using Laser doppler seanning (lark prestige company (Perimed societies) is produced, PeriScan PIMII) determines the CBF of the back of the hand before absorbing experiment sample. Then, allowed in control group (placebo) testee with 100mL water absorb together be colored as subject can not root The hard shell capsules of dextrin are filled with the hard shell capsules (gelatin system, same as below) differentiated according to color, allowed in other groups by reality The person of testing absorbs the hard shell capsules that each experiment sample is filled with the hard shell capsules of above-mentioned same colored with 100mL water together, at 30 points Zhong Hou, carry out measure same as described above after 60 minutes to the CBF of the back of the hand again.It should be noted that by above-mentioned camellia seed Extract (sample 3, sample 4), commercially available lipoic acid, lipoic acid lipid coating (sample 5), resveratrol extract (sample 7), (ball is apt to for commercially available ginkgo biloba p.e (You Ma biotech companies (PVC ー エ イ チ エ ヌ (strain)) production) and panax ginseng extractum Pharmaceutical Co., Ltd's (Wan Shan System medicines (strain)) production) as experiment sample.

The 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 are analyzed) by average value ± standard deviation.From the data of table 1, it is impossible to recognize For the back of the hand and the CBF significant changes of scalp of the subject that intake of placebo, but it intake of sample 3 or sample 4 The situation of (camellia seed extract), lipoic acid or sample 5 (lipoic acid lipid coating) and sample 7 (resveratrol extract) Under, blood flow facilitation and ginkgo biloba p.e is intake of or the situation of panax ginseng extractum reaches same degree, after intake 30 minutes And two times after 60 minutes, confirm that the value of the CBF of the back of the hand is significantly increased.

【Table 1】

Table 1 promotes the blood flow of the back of the hand the influence of (CBF)

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

The influence of the propagation to skin fiber sprout cell is investigated by the following method.That is, using Petri dishIn 10% fetal bovine serum of addition D-MEM culture mediums (SIGMA company (シ グ マ societies) produces, hypoglycemia) The adult skin fiber sprout cell of sowing normal person in (Daiichi Pure Chemicals Co., Ltd.'s (the first chemicals (strain)) production) (Kurashiki Boseki K.K. (Network ラ ボ ウ (strain)) produces, NHDF (NB).Hereinafter referred merely to as cell.)2×10⁵It is individual, cultivate 4 days To becoming closely to converge (about 80% density).Then, culture medium is removed, then is passed through by 5mL PBS cell twice After 0.02% EDTA solution 5mL cleaning cells, with 0.25% trypsin solution (NACALAI TESQUE Co., Ltd. (Na カ ラ イ テ ス Network (strain)) is produced) 5mL recovery cells, centrifuge (4 DEG C, 1000rpm, 5 minutes) and remove supernatant afterwards, lead to Cell is obtained after crossing PBS 2 times.The cell is cultivated repeatedly under these conditions and carries out squamous subculture.

Use 96 porocyte culture plates (0.32cm², Asahi Glass Co., Ltd (rising sun テ Network ノ グ ラ ス (strain)) production), With low blood serum medium, (Kurashiki Boseki K.K. (Network ラ ボ ウ (strain)) produces application on human skin fiber sprout cell propagation, in 500mL Skin fiber sprout cell basal medium (106S) in the addition of 10mL low serum propagation additive (LSGS) culture medium) Middle sowing 1 × 10⁴The above-mentioned squamous subculture cell in individual/hole, cultivates 24 hours.Then, culture medium is removed, is made most with the addition of The above-mentioned application on human skin fiber sprout cell propagation of the μ g/mL of final concentration of 5,10 or 20 each sample is further continued for training with low blood serum medium 48 hours are supported, afterwards, adding MTT solution (makes Thiazolyl blue (SIGMA company (シ グ マ societies) produces, reagent) be dissolved in PBS It is 5mg/mL to concentration) 25 μ L, 1 hour of culture.After by being decanted and removing culture medium completely, 100 μ L formazan solution are added (include 25% (v/v) 0.45M hac buffers, 25% (v/v) N,N-dimethylformamide, 10% (w/v) dodecyl sulphur Sour sodium.PH value is 4.5) to be stirred.Place at room temperature after 1 night, determine the absorbance in 590nm, evaluate the propagation journey of cell Degree.It should be noted that in the above-mentioned methods, D-MEM culture mediums and application on human skin fiber sprout cell propagation use low blood serum medium It is as the culture medium that with the addition of penicillin (ultimate density 100IU/mL) and streptomysin (ultimate density 0.1mg/mL), cell training Support in CO2gas incubator (37 DEG C, 5%CO₂Reinforcing gas phase under) in carry out.Here, above-mentioned collagen peptide (is tried Material 1, sample 2), camellia seed extract (sample 3, sample 4), commercially available lipoic acid, lipoic acid lipid coating (sample 5), sulphur The cyclodextrin inclusion compound (sample 6) of octanoic acid, resveratrol extract (sample 7), commercially available ginkgo biloba p.e (the biological skill of excellent horse Art company (ビ ー エ イ チ エ ヌ (strain)) production), carrot extract (Maruzen Pharmaceuticals Co., Ltd.'s (Wan Shan System medicines (strain)) it is raw Production) and sample 1 or sample 2 be used together with each sample as experiment sample.

The result is as shown in table 2, table 3, table 4.In the table, numerical value by with simultaneously implement check experiment (without In the case of sample) value represented as relative value when 100.In table 2, the ultimate density of sample 1 and sample 2 for 50 and 100 μ g/mL, also, by the addition of other samples in the medium, it is 5 and 10 μ g/mL to make ultimate density.In table 3 and table 4, with Sample 1 and sample 2 are 50 μ g/mL, and other samples are respectively added to 5 μ g/mL in the medium.

It is also considered as simultaneously in each addition concentration from the data of table 2, each sample makes the effect that skin fiber sprout cell breeds It is weak.

Also, from the data of table 3, in the case of sample 3~7 and lipoic acid are used together in sample 1, synergistically make fibre The effect of dimension sprout cell propagation becomes obvious.By being further used together sample 1 and sample 3, sample 7 and lipoic acid, the increasing Growing effect is strengthened.But, to ginkgo biloba p.e and carrot 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 the cultivation effect has the tendency of low.

It should be noted that being carried out instead of sample 1 or sample 2 using the collagen peptide that mean molecule quantity is about 300 Same experimental result is：It is with the tendency of the data of table 3 etc. that fiber sprout cell according to thing is used together, which breeds facilitation effect, It is same or higher (omitted data).

【Table 2】

Influence of each sample of table 2 to the propagation of skin fiber sprout cell

【Table 3】

Influence of the combination of table 3 and sample 1 to the propagation of fiber sprout cell

With sample 1 and sample	Absorbance (590nm)
		Control	100±3
Sample 3	127±8
		Sample 4	125±9
Sample 5	120±3
		Sample 6	121±4
Sample 7	122±7
		Lipoic acid	122±2
Ginkgo biloba p.e	105±1
		Panax ginseng extractum	106±3
Sample 3+ lipoic acids	146±8
		Sample 3+ samples 7	143±8
Lipoic acid+sample 7	141±8
		Sample 3+ lipoic acids+sample 7	161±8

【Table 4】

Influence of the combination of table 4 and sample 2 to the propagation of fiber sprout cell

With sample 2 and sample	Absorbance (590nm)
		Control	100±3
Sample 3	118±4
		Sample 4	117±6
Sample 5	113±4
		Sample 6	114±2
Sample 7	111±5
		Lipoic acid	116±5
Ginkgo biloba p.e	104±3
		Panax ginseng extractum	104±3
Sample 3+ lipoic acids	136±6
		Sample 3+ samples 7	132±9
Lipoic acid+sample 7	128±5
		Sample 3+ lipoic acids+sample 7	140±9

By above content, it specify that the combination according to collagen peptide of the invention and improving blood flow agent, particularly lead to Crossing Camellia extract, lipoic acid class, resveratrol has the effect of the significant propagation for promoting application on human skin fiber sprout cell.

Herein, although eliminate experimental data, but in this experimental example, by sample 1 or sample 2 and above-mentioned three kinds of blood Flow improvement result composition and situation compared with the situation for individually using it, it is thus identified that it is thin by application on human skin fibrous bud The ability of the generation collagen of born of the same parents and the ability of generation hyaluronic acid are significantly improved.

Experimental example 3 (is tested) to the U.S. flesh of people

It will obtain agreeing to participate in experiment as described below and skin elasticity and the low volunteer adult female 60 of amount of moisture (35 years old~55 years old, average age：48.6 years old), separated by 51 group, each group is absorbed each sample respectively, continued 6 weeks. Absorb sample front and rear with skin determination of viscoelasticity device (Germany, CK companies (Courage+Khazaka societies), trade name： CUTOMETER MPA580 (R)) skin elasticity is measured, also, the moisture of the predetermined position of face is filled with determination of moisture Put (Corneometer (R) CM825) and determine moisture relative value.It should be noted that this experiment is with above-mentioned sample 1, sample 3, examination Material 7, lipoic acid and combinations thereof, ginkgo biloba p.e same as described above and carry out.Intake is：Sample 1 is 5g, except this Sample in addition is 200mg, and in the case where being combined with sample 1, sample 1 is 5g, made together with sample 200mg in addition With.

The result is as shown in table 5.Skin elasticity and amount of moisture before and after sample intake are：It intake of except ginkgo leaf is extracted In the case of each sample beyond thing, compared with before intake, discovery has some improvement results after intake, but with absorbing preceding phase Than without big difference.But, in the case where being respectively combined with sample 1, skin elasticity and amount of moisture are substantially improved, clearly According to the combination of the collagen peptide of the present invention and improving blood flow agent, especially by with Camellia extract, lipoic acid class, white Veratryl alcohol is used together promotes U.S. flesh effect with significant.

【Table 5】

Influence (mean+/-standard error) of the table 5 to the skin of people

Study example 1 (soft capsule)

In above-mentioned sample 1 and the (mixing ratio of sample 3：10/1), sample 1 and the (mixing ratio of sample 7：10/1), sample 1 and sulphur Sad (mixing ratio：10/1), sample 1 and sample 3 and sample 7 and lipoic acid (mixing ratio：10/1/1/1) in any one 200 Add 50 parts of 40 parts of beeswax and evening primrose oil (EFAMOL companies of Britain (Britain エ Off ァ モ ー Le society)), heating mixing in part 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.The capsule preparations can be utilized as the dietary supplement of orally available intake, pharmaceuticals or animal feed.

Study example 2 (hard shell capsules)

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

Study example 3 (beverage)

It is separately added into the commercially available nourishing beverages of 100mL：Sample 1 and the (mixing ratio of sample 3：10/1), sample 1 and sample 7 (mixing ratios：10/1), sample 1 and lipoic acid (mixing ratio：10/1) each 1000mL, is sufficiently mixed and studies beverage.Even if by its Being preserved in refrigerator will not also find that outward appearance and local flavor are abnormal and unnatural for 6 months.This product can be as improving dry, bullet Property reduction, pachylosis etc. skin condition and/or promote the beverage or potus of U.S. flesh and be utilized.

Industrial applicability

Containing by collagen peptide and selected from above-mentioned specific three kinds of improving blood flow agent one or more kinds of groups Into of the invention U.S. flesh accelerator of the thing as active ingredient is used together, due to by the way that its orally ingestible or administration are had Improve drying, elasticity reduction, pachylosis and/or the effect for promoting U.S. flesh of skin, therefore, it is possible to diet product, pharmaceuticals, The field of non-pharmaceutical products, feed etc. is effectively utilized.

Claims (8)

1. a kind of U.S. flesh accelerator, it is characterised in that only contain collagen peptide and improving blood flow agent as active ingredient,

The improving blood flow agent is the one or two selected from the group being made up of camellia seed extract and lipoic acid class, institute It is the one or two selected from lipoic acid, its cyclodextrin inclusion compound to state lipoic acid class, and the lipoic acid is racemic modification.

2. U.S. flesh accelerator according to claim 1, it is characterised in that the lipoic acid class include from the lipoic acid, The outer surface of the one or two kinds of crystallizations, powder and/or the particle that are selected in the cyclodextrin inclusion compound is by lipid cladding The material of formation.

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

4. U.S. flesh accelerator according to claim 1, it is characterised in that the camellia seed extract be by water and/or Lower alcohol carries out the water composition obtained by extraction process to the degreasing dregs of rice of camellia seed.

5. the U.S. flesh accelerator according to claim 1 or 4, it is characterised in that the camellia seed extract is to contain saponin(e The extract of class, the saponins is containing by Tsubaki-saponin A1, Tsubaki-saponin A2, Tsubaki-saponin B1, Camelliasaponin B2, camellia The one or more kinds of saponinses selected in the group of saponin(e C1 and Tsubaki-saponin C2 compositions.

6. a kind of composition for oral administration of the U.S. flesh accelerator containing described in Claims 1 to 5 any one.

7. composition for oral administration according to claim 6, it is characterised in that the composition for oral administration is diet product.

8. a kind of beauty method, for the drying to skin, elasticity reduction, pachylosis skin condition improved and/or Promote U.S. flesh, it is characterised in that the U.S. flesh accelerator described in orally ingestible Claims 1 to 5 any one.