CN108697143A

CN108697143A - Including 3-O- galloyls -3,3 ', the Hydra composition of 5,5 ', 7- penta hydroxy group flavane

Info

Publication number: CN108697143A
Application number: CN201780013667.7A
Authority: CN
Inventors: 洪勇德; 崔敏植; 曹始永; 金正基
Original assignee: Amorepacific Corp
Current assignee: Amorepacific Corp
Priority date: 2016-07-20
Filing date: 2017-07-07
Publication date: 2018-10-23
Anticipated expiration: 2037-07-07
Also published as: WO2018016783A1; HK1254516A1; CN108697143B; JP2019520786A; JP7030692B2; KR20180010084A; KR102635190B1

Abstract

This specification relates in one aspect to include Hydra composition of the post-fermented tea ketone fraction as active ingredient, is on the other hand related to comprising from galloyl -3 3-O- that post-fermented tea ketone fraction detaches, 3 ', 5,5 ', 7- penta hydroxy group flavane (3-O-galloyl-3,3',5,5', 7-pentahydroxyflavan), the Hydra composition of its isomers, its acceptable salt, its prodrug, its hydrate or its solvate as active ingredient, this specification can be applied to and the relevant various fields such as skin moisture-keeping.

Description

Including 3-O- galloyls -3,3 ', the Hydra composition of 5,5 ', 7- penta hydroxy group flavane

Technical field

This specification is related to a kind of including 3-O- galloyls -3,3 ', 5,5 ', 7- penta hydroxy group flavane (3-O-galloyl-3,3', 5,5', 7-pentahydroxyflavan) Hydra composition.

Background technology

The skin of the mankind plays the barrier function from outer protection individual.Barrier function is for from external various thorns Swash the defence of (chemical substance, Air Pollutants, the environment of drying, ultraviolet light etc.) and prevents internal water excessive by skin The defencive function of diffusion, this defencive function is only in the case where the cuticula being made of keratinocyte is normally formed It could maintain its function.It is present in outermost cuticula (Stratum corneum, horney layer) in epidermis by cutin It forms the horn cell that cell forms, and terminated by differentiation and the lipid layer for surrounding the horn cell and constitutes (Mar celo C.L.et al,J.Invest.Dermatol.,80,pp37-44,1983).Keratinocyte generates day in cornification processes Right moisturizing factor (Natural moisturizing factor;) and intercellular lipid (ceramide, cholesterol, fat NMF Acid), to form cuticula, make cuticula that there is robustness and flexibility, to play as skin barrier (skin Barrier function).

This cuticula may pass through the atmosphere pollution of excessive living habits sexual factor or the drying such as wash one's face, have a bath Its function is easy loss due to disease in the environmental factors such as matter and allergic skin or such as geroderma, actually arrives The modern various factors due to further increasing complains dry skin symptom and the thus example of caused various interference recently In the presence of the trend gradually increased.

In order to maintain moisture of skin appropriate, various are externally supplied moisture or moisture is prevented to be lost in from internal Research, although actually exploitation have the various moisturizer (moisturizer) with water retention property, with to chemical substance The concern of harmfulness improves, and the moisturizing ingredient exploitation necessity from natural materials gradually increases, but this from natural materials Moisturizing ingredient research and development also deficiency be truth.

Invention content

The present invention is related to the moisturizing materials from natural materials on the one hand, is fractionated as a result, comprising post-fermented tea with providing For the purpose of the Hydra composition of object.

The present invention is on the other hand to provide comprising the 3-O- galloyls -3,3 ' detached from post-fermented tea fraction, 5,5 ', 7- Penta hydroxy group flavane (3-O-galloyl-3,3',5,5', 7-pentahydroxyf lavan) and Hydra group as active ingredient For the purpose of conjunction object.

In order to solve the above problems, the present invention provides skin moisture-keeping composition on the one hand, containing galloyl -3 3-O-, 3 ', 5,5 ', 7- penta hydroxy group flavane (3-O-galloyl-3,3',5,5', 7-pentahydroxyflava n), its isomers, its Acceptable salt, its prodrug, its hydrate, its solvate, comprising its post-fermented tea ketone fraction as active ingredient.

The present invention provides skin moisturization process on the other hand, wherein including:By 3-O- galloyls -3,3 ', 5,5 ', 7- five Hydroxyl flavane (3-O-galloyl-3,3',5,5', 7-pentahydroxyflavan), its isomers, its acceptable salt, its Prodrug, its hydrate, its solvate or comprising its post-fermented tea ketone fraction as active ingredient to individual carry out to Medicine.

The present invention provides the 3-O- galloyls -3,3 ' of the manufacture for skin moisture-keeping composition, 5,5 ', 7- on the other hand Penta hydroxy group flavane (3-O-galloyl-3,3',5,5', 7-pentahydroxyflavan), its isomers, its acceptable salt, The purposes of its prodrug, its hydrate, its solvate or the post-fermented tea ketone fraction comprising it.

The present invention on the other hand, as the active ingredient for skin moisture-keeping, provides galloyl -3 3-O-, and 3 ', 5,5 ', 7- Penta hydroxy group flavane (3-O-galloyl-3,3',5,5', 7-pentahydroxyflavan), its isomers, its acceptable salt, Its prodrug, its hydrate, its solvate or the post-fermented tea ketone fraction comprising it.

In addition, the present invention on the other hand, provides galloyl -3 3-O- as the active ingredient for skin moisture-keeping, 3 ', 5,5 ', 7- penta hydroxy group flavane (3-O-galloyl-3,3',5,5', 7-pentahydroxyflavan), its isomers, it can connect The non-therapeutic cosmetic of the salt, its prodrug, its hydrate, its solvate or the post-fermented tea ketone fraction comprising it received On the way.

The present invention provides the composition comprising post-fermented tea ketone fraction and the combination comprising specific compound on the one hand Object, so as to be widely used in moisturizing related field.

Description of the drawings

Fig. 1 be with high performance liquid chromatography to post-fermented tea extract analyzed as a result, indicating to be fractionated by acetone Situation and the case where be fractionated without acetone.

Fig. 2 indicates to utilize high capacity highly effective adverse current chromatogram (high-performance countercurrent Chromatography, HPCCC) chloroform of caffeine will be eliminated:Methanol 10:1 (v/v) fraction is divided into 10 sub- fractions.

Fig. 3 indicates the fraction 1 to 5 in the above-mentioned 10 sub- fractions using HPCCC fractionation.

Fig. 4 indicates the fraction 6 to 10 in the above-mentioned 10 sub- fractions using HPCCC fractionation.

Fig. 5 indicates trans- -3-O- galloyls -3,3 ', nuclear magnetic resonance (NMR) chart of 5,5 ', 7- penta hydroxy group flavane.

Specific implementation mode

In the following, being described in detail to this specification.

In this specification, " post-fermented tea " include using the other microorganisms or substance for being not present in enzyme in tealeaves into The tea of row fermentation.

In this specification, " ketone fraction " includes object obtained by being fractionated to predetermined substance or extract using ketone solvent Remaining substance after matter or fractionation, also comprising substance obtained by extracting these again with specific solvent.The type of above-mentioned ketone can To be any type, but preferably acetone, arbitrary side that fractional method and extracting method can be known to the skilled person Method.

In this specification, " isomers " includes not only especially optical isomer (optical isomers) (for example, base Pure mirror image isomer (essentially pure enantiomers), substantially pure partial stereoisomer in sheet (essentially pure diastereomers) or their mixture), also include rotamer (conformation Isomers) (that is, isomers that more than one chemical bond only has its angle different), position isomer (position Isomers) (especially tautomer (tautomers)) or geometric isomer (geometric isomers) are (for example, suitable Formula-transisomer).

In this specification, " substantially pure (essentially pure) " refers to for example about mirror image isomer or part In the case that isomers carries out use, the particular compound that can be used as mirror image isomer or partial allosteric body and enumerate exists about 90% or more, preferably from about 95% or more, even more preferably about 97% or more or about 98% or more, more preferably about 99% with On, still more preferably it is about 99.5% or more (w/w).

In this specification, " acceptable " refers to when being utilized with usual or medicine and pharmacology usage amount (dosage), by avoiding Comparable toxic effect can be used in animal, and the supervision that can obtain government or its approval in the mankind more specifically can be used The approval of mechanism has got the Green Light, or is identified as Codex Alimentarius (Food code), healthy function Codex Alimentarius or one As pharmacopeia in enumerate or be recorded in situation in other general literatures.

In this specification, " acceptable salt " refers to usual or pharmaceutically acceptable and has certain compound (parent Compound the salt according to an aspect of the present invention of preferred pharmacological activity).Above-mentioned salt can include (1) by such as hydrochloric acid, hydrogen The inorganic acids such as bromic acid, sulfuric acid, nitric acid, phosphoric acid are formed;Or by such as acetic acid, propionic acid, caproic acid, pentamethylene propionic acid, glycolic, acetone Acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3- (4- hydroxy benzenes first Acyl group) benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2- ethionic acids, 2- isethionic acids, benzene sulfonic acid, 4- chlorine Benzene sulfonic acid, 2- naphthalene sulfonic acids, 4- toluenesulfonic acids, camphorsulfonic acid, 4- Jia Jishuanhuans [2,2,2]Oct-2-ene -1- carboxylic acids, glucoheptose Acid, 3- phenylpropionic acids, trimethylace tonitric, butylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, water The acid-addition salts (acid addition salt) that the organic acids such as poplar acid, stearic acid, muconic acid are formed;Or (2) are present in mother The salt that acid proton in body compound is formed when substituted.

In this specification, " prodrug (prodrug) " is to instigate certain substance that chemical change occurs and adjust physical property, change The drug for learning property can pass through chemistry, physiology or enzyme in vivo although itself will not show physiological activity after administration Effect and become original drug to play drug effect.

In this specification, " hydrate (hydrate) " refers to the compound for being combined with water, is comprising between water and compound There is no the extensive concept of the interior packet compound of chemical binding force.

In this specification, " solvate " refer to solute molecule or ion and the molecule or ion of solvent between generate High-orderCompound.

An aspect of of the present present invention provides a kind of Hydra composition, and it includes the 3-O- galloyls-indicated by following chemical formula 1 3,3 ', 5,5 ', 7- penta hydroxy group flavane (3-O-galloyl-3,3',5,5', 7-pentahydroxyfla van), its isomers, Its acceptable salt, its pharmaceutically acceptable salt, its prodrug, its hydrate, its solvate or the post-fermented tea comprising it Ketone fraction is as active ingredient.Above-mentioned moisturizing includes skin moisture-keeping.

[Chemical formula 1]

According to a concrete example, above-mentioned post-fermented tea ketone fraction can be the water-insoluble extract for post-fermented tea Ketone fraction.

According to another concrete example, above-mentioned galloyl -3 3-O-, 3 ', 5,5 ', 7- penta hydroxy groups flavane can be by following chemical formula 2 Trans- -3-O- the galloyls -3,3 ' indicated, 5,5 ', 7- penta hydroxy group flavane (Trans-3-O-galloyl-3,3',5,5',7- pentahydroxyflavan)." flavane (flavan) " in this specification indicates above-mentioned 3-O- galloyls -3,3 ', 5,5 ', 7- five Hydroxyl flavane or trans- -3-O- galloyls -3,3 ', 5,5 ', 7- penta hydroxy group flavane.

[Chemical formula 2]

According to another concrete example, above-mentioned ketone fraction can be the alcohol extracting thing of ketone fraction.

According to another concrete example, above-mentioned ketone can include acetone, carvol (carvon), pulegone (pulegone), Isolongitolanone (isolongifolanone), 2-HEPTANONE, 2 pentanone, 3- cyclohexanone, 3- heptanone, 4- heptanone, methyln-hexyl ketone, 3- are pungent Ketone, methyl n-heptyl ketone, 3- nonanones, methyln nonyl ketone, methyl n-undecyl ketone, methyl isopropyl Ketone, ethyl isoamyl ketone, butylideneacetone, Methyl heptenone, dimethyl-octa ketenes, geranyl acetone, farnesyl acetone, 2,3- pentanediones, 2,3- cyclohexanediones, 3,4- Acetyl butyryl, 2,3- heptadione, amyl cyclopentanone, amyl cyclopentenone, 2- cyclopenta rings pentanone, hexyl cyclopentanone, 2- n-heptyls Cyclopentanone, cis-jasmone, dihydro jasmone, methyl cyclopentenyl ketone2- tert-butyl cyclohexanones, Para-tertiary butyl cyclohexanone, 2- sec-butyl cyclohexanones, apione, cryptone, orivone, 1- (3,5,6- trimethyls -3- Cyclohexene -1- bases) ethyl ketone, nerone, 4- cyclohexyl -4-methyl-2 pentanone, oxydone, epoxy IsophoroneMethyl naphthyl ketone, Alpha-Methyl anisal acetone, Anisylacetone, to methoxybenzene Benzylacetone, BENZYLIDENE ACETONE, acetanisole, melilotal, propiophenone, acetophenone, α-imperial court's ketone (Dynascone), iritone (lritone), ionone (ionone), pseudoionone (Pseudoionone), irone, Methyl iritone, 2,4- di-t-butyls cyclohexanone, allyl ionone, 2- acetyl group -3,3- dimethyl norbornane, Verbena officinalis Ketenes, fenchone (fenchon), cyclopentadecanone, ring hexadecene ketone etc. can include that all can usually make as in the field The mixture of the ketone of solvent and they can be preferably acetone.

According to another concrete example, above-mentioned alcohol can be the independent alcohol or mixture that can usually use in this field, can be with Preferably ethyl alcohol.

According to another concrete example, galloyl -3 3-O- in above-mentioned composition, 3 ', 5,5 ', 7- penta hydroxy groups flavane or trans- -3- O- galloyls -3,3 ', 5,5 ', 7- penta hydroxy groups flavane, its isomers, its acceptable salt, its pharmaceutically acceptable salt, before it Medicine, its hydrate or its solvate on the basis of above-mentioned composition total weight can be 0.000001 weight % or more, 0.000005 weight % or more, 0.00001 weight % or more, 0.00005 weight % or more, 0.0001 weight % or more, 0.0002 weight % or more, 0.0005 weight % or more, 0.001 weight % or more, 0.005 weight % or more, 0.01 weight % Above, 0.05 weight % or more, 0.1 weight % or more, 0.3 weight % or more, 0.5 weight % or more, 1 weight % or more, 1.5 Weight % or more, 1.8 weight % or more, 2 weight % or more, 2.2 weight % or more, 2.5 weight % or more, 2.8 weight % with Upper, 3 weight % or more, 3.2 weight % or more, 3.5 weight % or more, 3.8 weight % or more, 4 weight % or more, 4.2 weights Measure % or more, 4.5 weight % or more or 4.8 weight % or more or 5 weight % or less, 4.8 weight % or less, 4.5 weights Measure % or less, 4.2 weight % or less, 3.8 weight % or less, 3.5 weight % or less, 3.2 weight % or less, 3 weight % or less, 2.8 weight % or less, 2.5 weight % or less, 2.2 weight % or less, 2 weight % or less, 1.8 weight % or less, 1.5 weight % Below, 1.2 weight % or less, 1 weight % or less, 0.5 weight % or less, 0.3 weight % or less, 0.1 weight % or less, 0.05 Weight % or less, 0.01 weight % or less, 0.005 weight % or less, 0.001 weight % or less, 0.0005 weight % or less, 0.0002 weight % or less, 0.0001 weight % or less, 0.00005 weight % or less, 0.00001 weight % or less or 0.000005 weight % or less.Can be preferably 0.000001 to 5 weight %.

According to another concrete example, in above-mentioned composition, the content of post-fermented tea ketone fraction is relative to above-mentioned composition Total weight can be 0.01 weight % or more, 0.1 weight % or more, 1 weight % or more, 5 weight % or more, 10 weight % with Upper, 15 weight % or more, 20 weight % or more, 25 weight % or more, 30 weight % or more, 35 weight % or more, 40 weight % Above, 45 weight % or more, 50 weight % or more, 55 weight % or more, 60 weight % or more, 65 weight % or more, 70 weights % or more, 75 weight % or more, 80 weight % or more, 85 weight % or more, 90 weight % or more or 95 weight % or more are measured, Or 100 below weight %, 95 weight % or less, 90 weight % or less, 85 weight % or less, 80 weight % or less, 75 weights Measure % or less, 70 weight % or less, 65 weight % or less, 60 weight % or less, 55 weight % or less, 50 weight % or less, 45 Weight % or less, 40 weight % or less, 35 weight % or less, 30 weight % or less, 25 weight % or less, 20 weight % or less, 15 weight % or less, 10 weight % or less, 5 weight % or less, 1 weight % or less, 0.1 weight % or less or 0.05 weight % Below.Can be preferably 0.01 weight % to 100 weight %.

According to another concrete example, in above-mentioned fraction, galloyl -3 3-O-, 3 ', 5,5 ', 7- penta hydroxy groups flavane or trans- - 3-O- galloyls -3,3 ', 5,5 ', 7- penta hydroxy groups flavane, its isomers, its acceptable salt, its pharmaceutically acceptable salt, before it Medicine, its hydrate or its solvate can be 0.0001 weight % or more, 0.0002 weight on the basis of fraction total weight Measure % or more, 0.0005 weight % or more, 0.001 weight % or more, 0.005 weight % or more, 0.01 weight % or more, 0.05 Weight % or more, 0.1 weight % or more, 0.5 weight % or more, 1 weight % or more, 1.5 weight % or more, 2 weight % or more, 2.5 weight % or more, 3 weight % or more, 3.5 weight % or more, 4 weight % or more or 4.5 weight % or more or 5 weights Measure % or less, 4.5 weight % or less, 4 weight % or less, 3.5 weight % or less, 3 weight % or less, 2.5 weight % or less, 2 Weight % or less, 1.5 weight % or less, 1 weight % or less, 0.5 weight % or less, 0.1 weight % or less, 0.05 weight % with Under, 0.01 weight % or less, 0.005 weight % or less, 0.001 weight % or less, 0.0005 weight % or less or 0.0002 weight Measure % or less.0.0001 weight % can be preferably comprised to 5 weight %.

According to another concrete example, above-mentioned galloyl-3 3-O-, 3 ', 5,5 ', 7- penta hydroxy groups flavane or trans- galloyl-3-3-O-, 3 ', 5,5 ', 7- penta hydroxy group flavane, its isomers, its acceptable salt, its pharmaceutically acceptable salt, its prodrug, its hydration The dosage of object or its solvate can be 0.0001g/kg/ days or more, 0.001g/kg/ days or more, 0.01g/kg/ days with Upper, 0.1g/kg/ days or more, 1g/kg/ days or more, 2g/kg/ days or more, 3g/kg/ days or more, 4g/kg/ days or more, 5g/kg/ Its above, 6g/kg/ days or more, 7g/kg/ days or more, 8g/kg/ days or more, 9g/kg/ days or more, 10g/kg/ days or more, 11g/ Kg/ days or more, 12g/kg/ days or more, 13g/kg/ days or more or 14g/kg/ days or more or 15g/kg/ days or less, 14g/ Kg/ days or less, 13g/kg/ days or less, 12g/kg/ days or less, 11g/kg/ days or less, 10g/kg/ days or less, 9g/kg/ days with Under, 8g/kg/ days or less, 7g/kg/ days or less, 6g/kg/ days or less, 5g/kg/ days or less, 4g/kg/ days or less, 3g/kg/ days Below, 2g/kg/ days or less, 1g/kg/ days or less, 0.1g/kg/ days or less, 0.01g/kg/ days or less, 0.001g/kg/ days with Under or 0.0005g/kg/ days or less days.It can be preferably 0.0001g/kg/ days to 15mg/kg/ days.

According to another concrete example, above-mentioned moisturizing can be to supply and prevent any one in moisture loss based on moisturizing Kind or more.

An embodiment according to the present invention, using above-mentioned galloyl -3 3-O-, 3 ', 5,5 ', 7- penta hydroxy group flavane implements moisturizing Experiment as a result, when by galloyl -3 3-O- of the present invention, 3 ', 5, when 5 ', 7- penta hydroxy group flavane is coated on skin, can define true Recognize moisture of skin amount to dramatically increase (with reference to table 1), it can thus be appreciated that above-mentioned substance plays excellent moisturizing power.

Above-mentioned composition according to an aspect of the present invention can be pharmaceutical composition.Aforementioned pharmaceutical compositions can pass through Oral, non-oral, rectum, local, transdermal, intravenous, intramuscular, intraperitoneal, subcutaneous etc. are administered.For oral medication Dosage form can be tablet, pill, soft and hard rubber wafer, granule, powder, fine granule, liquor, opacifiers or micropill preparation, But not limited to this.Dosage form for non-oral administration can be solution, suspending agent, emulsion agent, gel, injection, point Drops, suppository, patch, ointment or spray, but not limited to this.Above-mentioned dosage form can be according to the common side in the field Method is easily manufactured, can also include surfactant, excipient, hydrating agents, emulsification promoter, suspending agent, for adjust ooze Salt or buffer, colorant, spice, stabilizer, preservative, preservative agent or the other common auxiliary agents pressed thoroughly.

The dosage of above-mentioned composition according to an aspect of the present invention or dosage according to age of the object being administered, Gender, weight, pathological state and its seriousness, administration route or the judgement of prescriber and it is different.It is suitable based on this factor The determination of dosage is in the level of those skilled in the art, one day administration dosage of active ingredient, such as can be 0.001 μ g/ Kg/ days to 5000mg/kg/ days, can be 0.0001mg/kg/ days to 15mg/kg/ days, but be not limited to more specifically This.

According to another concrete example, above-mentioned composition can be food compositions or health food composition.

The dosage form of above-mentioned food compositions or health food composition is not particularly limited, for example, can be made tablet, The dosage forms such as the liquors such as granula, pill, powder agent, capsule, potus, caramel, gel, stick, tea bag.Those skilled in the art can be with According to dosage form or use purpose, without difficulty in the food compositions or health food composition of each dosage form in addition to effective Usually used ingredient is suitably selected and is coordinated in the field other than ingredient, the case where being applied simultaneously with other raw materials Under, it may occur however that synergy.

Above-mentioned composition can by simply absorbing, drinking, drug administration by injection, spray delivery or squeeze administration etc. various methods It is administered.

In food compositions or health food composition according to an aspect of the present invention, the dosage of above-mentioned active ingredient It determines in the level of those skilled in the art, dosage, which is administered, for example in one day to be 0.0001mg/kg/ days to 15mg/kg/ It, but not limited to this, can be different according to various factors such as the age of object to be administered, health status, complication.

Food compositions according to an aspect of the present invention or health food composition, such as can be chewing gum, caramel The various foodstuffs such as product, confectionery, ice cream class, Biscuits can also be the beverages systems such as cold drink, mineral water, alcoholic beverage Product include the healthy food class of vitamin or minerals etc..

In addition to the foregoing, according to an aspect of the present invention food compositions or health food composition can include each The fragrance such as kind of nutritional agents, vitamin, minerals (electrolyte), synthetic perfume and natural perfume material, colorant and thickener (cheese, Chocolate etc.), pectic acid and its salt, alginic acid and its salt, organic acid, protective colloid tackifier, pH adjusting agent, stabilizer, Preservative, glycerine, alcohol, the carbonating agent etc. for soda.In addition to this, Combined food according to an aspect of the present invention Object can also include for manufacturing fruit juice, fruit drink and the pulp of vegetable beverage.This ingredient can be alone or in combination It uses.Although the ratio of this additive is not critically important, under normal circumstances, according to the present invention the one of every 100 parts by weight The composition of aspect includes in the range of 0 to about 50 parts by weight.

According to another concrete example, above-mentioned composition can be Dermatologic preparation composition.Dermatologic preparation composition can be with For the composition in cosmetics, oral agents, detergent, medicine and pharmacy etc., but not limited to this.Above-mentioned skin preparations for extenal use Dosage form is not particularly limited, such as smoothing toner, firming lotion, alimentary water, nourishing cream, massage cream, essence, eye cream, eye can be made The cosmetics such as portion's essence, make-up remover, makeup removing foam, makeup remover, facial mask, powder, body lotion, skin cream, soothing oil and U.S. flesh essence.

In addition, the Dermatologic preparation composition of this specification can also include selected from functional salt for special purpose (salt) and one or more of the pH adjusting agent for adjusting pH.At this moment, above-mentioned salt can be selected from for ion shielding, protect Inorganic salts, organic salt and/or the organic-inorganic salt of wet, ultraviolet light blocking etc..Concrete example, above-mentioned salt can be selected from sodium chloride (NaCl), sodium phosphate (Na₃PO₄) and calcium chloride (CaCl₂) etc..Above-mentioned pH adjusting agent is selected from sour (aicd) or alkali (base), such as Hydrochloric acid, sulfuric acid, tartaric acid, citric acid, phosphoric acid, acetic acid, lactic acid, sodium lactate, sodium hydroxide, potassium hydroxide, alkyl can be selected from Amine, alkanolamine and ammonium hydroxide etc..

The Dermatologic preparation composition of this specification can be cosmetics, pharmaceutically or medical exterior-applied article composition.It is above-mentioned Cosmetics, pharmaceutically or medical exterior-applied article composition can also contain preservative, stabilizer, hydrating agents or emulsification promoter, use In substance useful on the auxiliary agents such as the salt and/or buffer for adjusting osmotic pressure and other treatments.Breast can be made in above-mentioned composition The dosage forms such as liquid, frost, ointment or gel.The above-mentioned preferred cutaneous penetration of Dermatologic preparation composition.

It is above-mentioned pharmaceutically or the dosage of the active ingredient of medical exterior-applied article composition is according to year of the object for receiving treatment Age, gender, weight, specified disease to be treated or pathological state, the severity of disease or pathological state, administration route and prescription The judgement of doctor and it is different.Dosage based on this factor is determined within the level of those skilled in the art.Usually In the case of, the dosage of above-mentioned active ingredient can be in 0.0001mg/kg/ days to 15mg/kg/ days ranges, but are not limited to This.

In the one side of this specification, composition is not particularly limited in terms of dosage form, can be cosmetic composition. Above-mentioned cosmetic composition is used as such as skin and/or hair hair composition, such as can be smoothing toner, firming lotion, nourishing Water, nourishing cream, massage cream, eye cream, eye essence, essence, make-up remover, makeup removing breast, makeup removing foam, makeup remover, facial mask, powder, body Body breast, skin cream, U.S. flesh essence, shower cream, hair dye, shampoo, hair conditioner, hair styling agent, preparation for baldness, ointment, gel, The dosage forms such as frost, patch, spray and adhering skin type, but not limited to this.

In addition, those skilled in the art can be according to the type of other external preparations or using purpose, without difficulty to each Other ingredients in a dosage form other than above-mentioned required ingredient properly select and coordinate.

Can be cosmetic composition according to the above-mentioned composition of this specification, above-mentioned cosmetic composition can be to be suitble to Locally applicable whole dosage forms provide.For example, lotion obtained from water phase can be scattered in solution, by oil phase, divide water phase Dissipate lotion, suspension, solid, gel, powder, paste, micropin, foam (foam) or aerosol composition obtained from oil phase Dosage form.The composition of this dosage form can be manufactured according to the conventional method in the field.

It, can be with other than the compound of this specification or fraction according in the cosmetic composition of this specification Including the ingredient that functional additive and general cosmetic composition are included.As above-mentioned functional additive, can wrap Containing the ingredient in water soluble vitamin, fat soluble vitamin, pdef polypeptide, polymerization polysaccharide, sphingolipid and marine algae extract.According to For the cosmetic composition of this specification in the range of not influencing its main effect, can preferably comprise can be to main effect band Carry out other ingredients of synergy.In addition, according to the cosmetic composition of this specification can also include moisturizer, emollient, Surfactant, ultra-violet absorber, preservative, fungicide, antioxidant, pH adjusting agent, organic and inorganic pigment, fragrance, Cooling agent or antiperspirant.The use level of mentioned component is not in the range of influencing the purpose and effect of this specification, this field skill Art personnel can be readily selected, and use level can be 0.001 to 10 weight % on the basis of composition total weight, specifically Can be 0.01 to 3 weight %.

The composition and effect of this specification are more specifically illustrated in the following, enumerating embodiment, experimental example and dosage form example. But these examples only with help understand this specification illustration purpose and be provided, the scope of this specification and Range is not limited to following examples.

<Embodiment 1>The manufacture of post-fermented tea sample

Water is added in the green tea made of green tea (Camellia sinensis var.Yabukita) leaf and by moisture Content is adjusted to 40 weight %.It is inoculated with 5 × 10 herein⁶The bacillus subtilis (Bacillus subtillis) of cfu/g, 50 DEG C fermentation 3 days after, fermented at 80 DEG C 4 days.It is 4 weights to be dried the tea of fermentation to moisture with 70 DEG C to 80 DEG C of hot winds After measuring % to 6 weight %, cured at 10 DEG C 100 days.

The tea sample of above-mentioned curing is crushed 15 seconds, is sieved with the stainless steel of mesh size 1mm.Then, by powder Broken 50mg is added in the microcentrifugal tube (Eppendorf tube) of 1.5ml, adds the deionized water of 1ml, in 60 DEG C of perseverances After being stirred 30 minutes with constant speed in warm water tank, centrifugation in 15 minutes has been carried out with 13000rpm at 25 DEG C.From drying Fermentation green-tea extract in only detached part not soluble in water.

<Embodiment 2>Fraction acquisition is detached with compound

The above-mentioned post-fermented tea sample of 150g is fractionated with acetone and is eliminated as much as catechin-derived object and coffee Cause obtains the soluble matter of flavonoids concentration.For the above-mentioned acetone soluble matter of 40g, using silica gel column chromatography, by chloroform:Methanol Mixture as solvent, with 10:1,5:1,1:The sequence of 1 (v/v), which is dissolved out, has obtained each fraction.

Herein, with high performance liquid chromatography (high performance liquid chromatography, HPLC, Waters Alliance 2695system, Waters, USA) to the chloroform of 12g:Methanol 10:1 (v/v) fraction is analyzed As a result, in the case where not being fractionated as described above with acetone, it is still caffeine and exists as main compound, as above Confirm that caffeine has removed (Fig. 1) after the fractionation using acetone.

Utilize high capacity highly effective adverse current chromatogram (high-performance countercurrent Chromatography, HPCCC, Dynamic Extractions Ltd, UK) it is fractionated the chloroform for eliminating caffeine of 8.9g: Methanol 10:1 (v/v) fraction.At this moment the solvent used is n-hexane-TBME (methyl tertiary butyl ether(MTBE))-BuOH-MeCN- water (0.25:3:1:1:5, v/v), flow velocity 25ml/min.Using above-mentioned condition, totally 10 sub- fractions (Fig. 2) are separated, HPLC is used It is analyzed, it is thus identified that the compound contained by each fraction is largely flavonoids (flavonoid) system (Fig. 3, Fig. 4).

Trans- -3-O- galloyls -3,3 ', 5,5 ', 7- penta hydroxy group flavane (Trans-3-O- are isolated by above-mentioned fraction galloyl-3,3',5,5',7-pentahydroxyflavan,C₂₂H₁₈O₁₀, molecular weight 442.0900), the compound of separation Structure is as follows.

[Chemical formula 2]

¹In the case of H nuclear magnetic resonance (nuclear magnetic resonance, NMR), as solvent (solvent) methanol-d3 (methanol-d3) has been used, equipment has used Bruker Advance DPX-500, and (BRUKER is public Department, USA), trans- galloyl-3-3-O-, 3 ', 5, the NMR data of 5 ', 7- penta hydroxy group flavane is as follows, specific chart such as Fig. 5.

¹H NMRδ(500Hz)7.01(s,2H),6.89(s,1H),6.76(s,2H),6.04(s,1H),5.96(s,1H), 5.36(m,1H),5.13(m,1H),2.83(m,1H),2.73(m,1H)

<Experimental example 1>Skin moisturization is evaluated

In order to understand above-mentioned trans- galloyl-3-3-O-, 3 ', 5, the skin moisturization of 5 ', 7- penta hydroxy group flavane will be above-mentioned Trans- -3-O- galloyls -3,3 ', 5,5 ', 7- penta hydroxy group flavane are coated on 20~30 years old of 14 (man 7, woman 7) health 3 positions of the lower facies medialis brachii 3X3 ㎝ squares of adult men and women.

Specifically, as substances, by above-mentioned trans- galloyl-3-3-O-, 3 ', 5,5 ', 7- penta hydroxy groups flavane with 0.2% concentration is diluted and uses, and as positive controls, has used glycerine 5%.At the initial stage of substances, under State method skin moisture tester (Corneometer CM825 (Courage+Khazaka electronic GmbH, moral State)) determine 2 days after, the moisture of skin amount after 7 days, after 11 days.

The measuring principle of skin moisture tester is, for the amount of existing moisture in the epidermis of skin, to utilize electrical side Method measures the ion degree of moisture, the amount of moisture is quantized and calculated, to measure moisturizing power.First, wanting to survey The detector (probe) of skin moisture tester is placed on fixed skin part.Pass through sensing when squeezing skin with detector Device and the conductivity of skin are quantized and are shown on picture, 3 times are repeatedly measured at each position and find out average value.It is tied Fruit is shown in following table 1.

[Table 1]

It can confirm from above-mentioned table, when by trans- galloyl-3-3-O-, 3 ', 5,5 ', 7- penta hydroxy group flavane is coated on skin When, moisture of skin amount shows statistically significantly increased trend (paired-samples T-test (paired T-test), p<0.01), exist Coating also maintains moisture of skin amount after 11 days.Therefore, it is known that according to this specification include trans- galloyl-3-3-O-, 3 ', 5, The composition of 5 ', 7- penta hydroxy group flavane effectively preserves the moisture of skin after coating and skin moisture-keeping power is excellent.

<Dosage form example 1>Soft capsule

To post-fermented tea acetone fraction 150mg, lactose 440mg, the cornstarch according to this specification embodiment 2 430mg and magnesium stearate 2mg are mixed and have been manufactured soft capsule filling liquid.In addition, above-mentioned steps are different from, with gelatin 66 The ratio of 10 parts by weight of parts by weight, 24 parts by weight of glycerine and Sorbitol solution manufactures soft balsam capsule skin, fills above-mentioned filling liquid, to Soft capsule is manufactured.

In addition, to trans- galloyl-3-3-O- according to this specification embodiment, 3 ', 5,5 ', 7- penta hydroxy group flavane 3mg, breast Sugared 440mg, cornstarch 450mg and magnesium stearate 2mg are mixed and are manufactured soft capsule filling liquid.Moreover, with above-mentioned side Legal system makes soft capsule skin, fills above-mentioned filling liquid, to manufacture soft capsule.

<Dosage form example 2>Tablet

To post-fermented tea acetone fraction 150mg, vitamin e1 5mg, the vitamin C according to this specification embodiment 2 15mg, galactooligosaccharicomposition 250mg, lactose 60mg and maltose 140mg are mixed, and are granulated using fluid bed dryer Afterwards, it is added to sugar ester (sugar ester) 8mg.The composition is subjected to film-making with usual way and has manufactured tablet.

In addition, to trans- galloyl-3-3-O- of embodiment, 3 ', 5,5 ', 7- penta hydroxy group flavane 3mg, vitamin E 15mg, Vitamin C 15mg, galactooligosaccharicomposition 259mg, lactose 60mg and maltose 140mg are mixed, using fluid bed dryer into After row granulating, it is added to sugar ester (sugar ester) 8mg.The composition is subjected to film-making with conventional method and has manufactured piece Agent.

<Dosage form example 3>Potus

To post-fermented tea acetone fraction 80mg, vitamin E 9mg, the vitamin C according to this specification embodiment 2 After 9mg, glucose 10g, citric acid 0.6g and liquid oligosaccharides 25g are mixed, the pure water that 400ml is added is filled. After being filled into bottle, sterilizes 4~5 seconds at 30 DEG C and manufactured potus.

In addition, to trans- galloyl-3-3-O- of embodiment, 3 ', 5,5 ', 7- penta hydroxy group flavane 0.1mg, vitamin E 9mg, After vitamin C 9mg, glucose 10g, citric acid 0.6g and liquid oligosaccharides 25g are mixed, the pure water of 400ml is added, with The mode of every bottle of 200ml is filled.It sterilizes 4~5 seconds at 30 DEG C after being filled into bottle and has manufactured potus.

<Dosage form example 4>Granule

To post-fermented tea acetone fraction 150mg, vitamin E 9mg, the vitamin C according to this specification embodiment 2 9mg, anhydrous crystal glucose 250mg and starch 550mg are mixed, after being shaped to particle using fluid bed granulate machine, filling Granule has been manufactured in bag.

In addition, to trans- galloyl-3-3-O- of embodiment, 3 ', 5,5 ', 7- penta hydroxy group flavane 3mg, vitamin E 9mg, dimension Raw element C 9mg, anhydrous crystal glucose 250mg and starch 550mg are mixed, and particle is shaped to using fluid bed granulate machine Afterwards, it is filled into bag and has manufactured granule.

<Dosage form example 5>Injection

Composition recorded in following table 2 has manufactured injection with conventional method.

[Table 2]

Gradation composition	Content
		According to the post-fermented tea acetone fraction of embodiment 2	100mg
Injection sterile purified water	In right amount
		PH adjusting agent	In right amount

In addition, trans- galloyl-3-3-O- of the embodiment using 3mg, 3 ', 5,5 ', 7- penta hydroxy group flavane replace it is above-mentioned after Fermented tea acetone fraction and manufactured injection.

<Dosage form example 6>Healthy food

According to the composition described in following Table 3, healthy food has been manufactured with conventional method.

[Table 3]

In addition, trans- galloyl-3-3-O- of the embodiment using 3mg, 3 ', 5,5 ', 7- penta hydroxy group flavane replace it is above-mentioned after Fermented tea acetone fraction, to manufacture healthy food.

About the ratio of components of said vitamin and inanimate matter mixture, to be relatively suitble to the ingredient of healthy food as an example And composition is mixed, but its match ratio can be implemented with random variation, be mixed according to conventional healthy food manufacturing method above-mentioned After ingredient, it is used for according to the conventional method in health food composition manufacture.

<Dosage form example 7>Healthy beverage

[Table 4]

Ingredient	Content
		According to the post-fermented tea acetone fraction of embodiment 2	50mg
Citric acid	1000mg
		Oligosaccharide	100g
Plum fruit concentrate	2g
		Taurine	1g
Pure water	Surplus
		Total volume	900ml

As shown in Table 4 above, the pure water for adding surplus makes total volume become 900ml, according to conventional healthy beverage After manufacturing method mixes above-mentioned ingredient, after 85 DEG C of agitating and heatings about 1 hour, manufactured solution is filtered, is taken to the 2 of sterilizing It rises in container, after sealing sterilizing, refrigeration keeping, to manufacture healthy beverage.

In addition, trans- galloyl-3-3-O- of the embodiment using 0.1mg, 3 ', 5,5 ', 7- penta hydroxy group flavane replaces above-mentioned Post-fermented tea acetone fraction, to manufacture healthy beverage.

<Dosage form example 8>Smoothing toner (moisturizing lotion)

Utilize 3 weight % of post-fermented tea acetone fraction, the L-AA -2- phosphoric acid magnesium salts 1.00 according to embodiment 2 Weight %, water solubility collagen (1% aqueous solution) 1.00 weight %, 0.10 weight % of sodium citrate, 0.05 weight of citric acid Amount %, 0.20 weight % of licorice, 3.00 weight % of 1,3-BDO, surplus pure water manufactured smoothing toner (moisturizing Lotion).

In addition, trans- galloyl-3-3-O- of the embodiment using 0.1 weight %, 3 ', 5,5 ', 7- penta hydroxy group flavane replaces Above-mentioned post-fermented tea acetone fraction, to manufacture smoothing toner.

<Dosage form example 9>White type preparation

Use 3.00 weight % of post-fermented tea acetone fraction, the polyethylene glycol mono stearate 2.00 according to embodiment 2 Weight %, 5.00 weight % of self-emulsifying glycerol monostearate, 4.00 weight % of propylene glycol, 6.00 weight % of squalene, three -2- second 6.00 weight % of base hexane glyceride, 1.00 weight % of glycosyl sphingolipid, 7.00 weight % of 1,3-BDO, 5.00 weight % of beeswax, The pure water of surplus, to manufacture white type preparation.

In addition, using trans- galloyl-3-3-O- of the O.1 embodiment of weight %, 3 ', 5,5 ', 7- penta hydroxy group flavane replaces Above-mentioned post-fermented tea acetone fraction, to manufacture white type preparation.

<Dosage form example 10>Facial mask

Using according to the 3.00 weight % of post-fermented tea acetone fraction of embodiment 2,13.00 weight %, L- of polyvinyl alcohol 1.00 weight % of ascorbic acid -2- phosphoric acid magnesium salts, 1.00 weight % of lauroyl hydroxyproline, (1% is water-soluble for water-soluble collagen Liquid) 2.00 weight %, 3.00 weight % of 1,3-BDO, 5.00 weight % of ethyl alcohol, surplus pure water, to manufacture face Film.

In addition, trans- galloyl-3-3-O- of the embodiment using 0.1 weight %, 3 ', 5,5 ', 7- penta hydroxy group flavane replaces Above-mentioned post-fermented tea acetone fraction, to manufacture facial mask.

The specific part of this specification is illustrated in detail above, to those skilled in the art, this The specific technology of kind is preferred embodiment, and it is obvious that the range of this specification, which will not be defined in this,.Therefore, this explanation The substantial range of book is based on appended claims and its equivalent is defined.

Claims

1. a kind of Hydra composition, contain galloyl -3 3-O- indicated by following chemical formula 1,3 ', 5,5 ', 7- penta hydroxy groups are yellow Alkane, its isomers, its acceptable salt, its prodrug, its hydrate, its solvate are fractionated comprising its post-fermented tea ketone Object as active ingredient,

Chemical formula 1

2. composition according to claim 1, wherein the post-fermented tea ketone fraction is for the non-aqueous of post-fermented tea The ketone fraction of soluble extract.

3. composition according to claim 1, wherein the ketone is acetone.

4. composition according to claim 1, wherein galloyl -3 3-O-, 3 ', 5,5 ', 7- penta hydroxy group flavane is served as reasons Trans- galloyl-3-3-O- that following chemical formula 2 indicates, 3 ', 5,5 ', 7- penta hydroxy group flavane,

Chemical formula 2

5. composition according to claim 1, wherein in the composition, galloyl -3 3-O-, 3 ', 5,5 ', 7- pentahydroxy-s Base flavane, its isomers, its acceptable salt, its prodrug, its hydrate or its solvate content relative to the combination Object total weight is 0.000001 weight % to 5 weight %.

6. composition according to claim 1, wherein in the composition, the content phase of post-fermented tea ketone fraction It is 0.01 weight % to 100 weight % for the composition total weight.

7. composition according to claim 1, wherein in the fraction, galloyl -3 3-O-, 3 ', 5,5 ', 7- Penta hydroxy group flavane, its isomers, its acceptable salt, its prodrug, its hydrate or its solvate are with fraction total weight Benchmark includes 0.0001 weight % to 5 weight %.

8. composition according to claim 1, wherein galloyl -3 3-O-, 3 ', 5,5 ', 7- penta hydroxy groups flavane, its is different Structure body, its acceptable salt, its prodrug, its hydrate or its solvate dosage be 0.0001mg/kg/ days to 15mg/ Kg/ days.

9. composition according to any one of claim 1 to 8, wherein the composition is food compositions.

10. composition according to any one of claim 1 to 8, wherein the composition is pharmaceutical composition.

11. composition according to any one of claim 1 to 8, wherein the composition is cosmetic composition.