CN108697143B

CN108697143B - Moisturizing compositions comprising 3-O-galloyl-3,3', 5',7-pentahydroxyflavan

Info

Publication number: CN108697143B
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: 2023-09-12
Anticipated expiration: 2037-07-07
Also published as: JP7030692B2; WO2018016783A1; JP2019520786A; HK1254516A1; KR102635190B1; CN108697143A; KR20180010084A

Abstract

The present specification relates to a moisturizing composition comprising a post-fermented tea-ketone fraction as an active ingredient, and relates to a moisturizing composition comprising 3-O-galloyl-3,3', 5',7-pentahydroxy flavan (3-O-galloyl-3, 3', 5',7-pentahydroxy flavan), an isomer thereof, an acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof isolated from the post-fermented tea-ketone fraction as an active ingredient, and is applicable to various fields related to skin moisturization and the like.

Description

Moisturizing compositions comprising 3-O-galloyl-3,3', 5',7-pentahydroxyflavan

Technical Field

The present specification relates to a moisturizing composition comprising 3-O-galloyl-3,3', 5',7-pentahydroxyflavan (3-O-galloyl-3, 3', 5', 7-pentahydroxyflavan).

Background

The human skin performs a barrier function that protects individuals from the outside. The barrier function is a protective function against various stimuli (chemical substances, atmospheric pollutants, dry environment, ultraviolet rays, etc.) from the outside and preventing excessive diffusion of moisture in the body through the skin, and this protective function can be maintained only in the case where the stratum corneum composed of keratinocytes is normally formed. The outermost Stratum corneum (horney layer) present in the epidermis is formed by keratinocytes, and is composed of differentiated keratinocytes and a lipid layer surrounding the keratinocytes (marcelo c.l.et al, j. Invest. Dermatol.,80, pp37-44,1983). Keratinocytes produce natural moisturizing factors (Natural moisturizing factor; NMF) and intercellular lipids (ceramides, cholesterol, fatty acids) during keratinization, thereby forming the stratum corneum, which is firm and flexible, thus functioning as a skin barrier.

Such stratum corneum may be liable to lose its function by an excessively habitual factor of life such as washing and bathing or an environmental factor such as a dry atmosphere pollutant, and an allergic skin or an internal disease such as aged skin, and in fact, there is a tendency that the recent complaints of dry skin symptoms and various disturbances caused thereby are gradually increased due to various factors further increased in modern times.

In order to maintain an appropriate skin moisture, various studies have been made to supply moisture from the outside or prevent moisture from losing from the body, and various moisturizers (moisturers) having a moisture retaining property have been developed in practice, but as the concern about the harmfulness of chemical substances increases, the necessity of development of moisture retaining components derived from natural substances has been increasing, but such research and development of moisture retaining components derived from natural substances has been insufficient.

Disclosure of Invention

The present invention relates in one aspect to a moisturizing material derived from natural materials, whereby the object is to provide a moisturizing composition comprising post-fermented tea fractions.

In another aspect, the present invention aims to provide a moisturizing composition comprising 3-O-galloyl-3,3', 5',7-pentahydroxyflavan (3-O-galloyl-3, 3', 5',7-pentahydroxyf lavan) isolated from post-fermented tea fractions as an active ingredient.

In order to solve the above problems, the present invention provides a composition for moisturizing skin comprising 3-O-galloyl-3,3', 5',7-pentahydroxyflavan (3-O-galloyl-3, 3', 5',7-pentahydroxyflava n), an isomer thereof, an acceptable salt thereof, a prodrug thereof, a hydrate thereof, a solvate thereof, and a post-fermented tea ketone fraction comprising the same as an active ingredient.

The present invention provides in another aspect a method of moisturizing skin comprising: 3-O-galloyl-3,3', 5',7-pentahydroxyflavan (3-O-galloyl-3, 3', 5', 7-pentahydroxyflavan), an isomer thereof, an acceptable salt thereof, a prodrug thereof, a hydrate thereof, a solvate thereof, or a post-fermented tea ketone fraction comprising the same is administered to an individual as an active ingredient.

In another aspect the present invention provides the use of 3-O-galloyl-3,3', 5',7-pentahydroxyflavan (3-O-galloyl-3, 3', 5', 7-pentahydroxyflavan), isomers thereof, acceptable salts thereof, prodrugs thereof, hydrates thereof, solvates thereof, or post fermented tea ketone fractions comprising the same for the manufacture of a composition for skin moisturisation.

In another aspect of the present invention, 3-O-galloyl-3,3', 5',7-pentahydroxyflavan (3-O-galloyl-3, 3', 5', 7-pentahydroxyflavan), isomers thereof, acceptable salts thereof, prodrugs thereof, hydrates thereof, solvates thereof, or post-fermented tea ketone fractions comprising the same are provided as an active ingredient for skin moisturization.

In addition, in another aspect, the present invention provides a non-therapeutic cosmetic use of 3-O-galloyl-3,3', 5',7-pentahydroxyflavan (3-O-galloyl-3, 3', 5', 7-pentahydroxyflavan), an isomer thereof, an acceptable salt thereof, a prodrug thereof, a hydrate thereof, a solvate thereof, or a post-fermented tea ketone fraction comprising the same as an active ingredient for skin moisturization.

The present invention provides, in one aspect, a composition comprising post-fermented tea ketone fraction and a composition comprising specific compounds, thereby being capable of being widely applied to the related field of moisture preservation.

Drawings

FIG. 1 shows the results of analysis of post-fermented tea extract by high performance liquid chromatography, showing the case of acetone fractionation and the case of no acetone fractionation.

FIG. 2 shows the removal of caffeine from chloroform using high-capacity high-performance countercurrent chromatography (high-performance countercurrent chromatography, HPCCC): the methanol 10:1 (v/v) fraction was divided into 10 subfractions.

FIG. 3 shows fractions 1 to 5 of the 10 subfractions described above, fractionated using HPCCC.

Fig. 4 shows fractions 6 to 10 of the above 10 subfractions fractionated using HPCCC.

FIG. 5 shows Nuclear Magnetic Resonance (NMR) chart of trans-3-O-galloyl-3,3', 5', 7-pentahydroxyflavan.

Detailed Description

The present specification will be described in detail below.

In this specification, "post-fermented tea" includes tea that is fermented with other microorganisms or substances that are not enzymes present in tea leaves.

In the present specification, the term "ketone fraction" includes a substance obtained by fractionating a specific substance or extract with a ketone solvent or a substance remaining after fractionation, and also includes a substance obtained by re-extracting the substance with a specific solvent. The kind of the above ketone may be any, but is preferably acetone, and the fractionation method and the extraction method may be any methods known to those skilled in the art.

In this specification, "isomers" include not only optical isomers (e.g., substantially pure mirror isomers (essentially pure enantiomers), substantially pure partial stereoisomers (essentially pure diastereomers), or mixtures thereof), but also conformational isomers (conformation isomers) (i.e., isomers where more than one chemical bond differs only in angle), positional isomers (positional isomers), particularly tautomers (tauometers), or geometric isomers (geometric isomers) (e.g., cis-trans isomers), among others.

In the present specification, "substantially pure" means that, for example, when the enantiomer or partial isomer is used, about 90% or more, preferably about 95% or more, more preferably about 97% or more or about 98% or more, still more preferably about 99% or more, still more preferably about 99.5% or more (w/w) of the specific compound which can be exemplified as the enantiomer or partial isomer exists.

In the present specification, "acceptable" means that the composition is used in an amount of usual or pharmaceutically acceptable use (dosage), and can be used for animals, more specifically, for humans, by avoiding considerable toxic effects, or can be approved or obtained by a regulatory agency capable of obtaining government or approval thereof, or can be recognized as a Food code, health function Food code, or as listed or described in other general documents in general pharmacopoeia.

In the present specification, "acceptable salt" refers to a salt according to an aspect of the present invention which is generally or pharmaceutically acceptable and has a preferable pharmacological activity of a certain compound (parent compound). The above-mentioned salt may contain (1) a salt formed from an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or acid addition salts (acid addition salt) formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3- (4-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1, 2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo [2, 2] -oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, t-butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid; or (2) salts formed when acidic protons present in the parent compound are substituted.

In the present specification, "prodrug" refers to a drug that chemically changes a substance to regulate physical and chemical properties, and is capable of becoming an original drug in vivo by chemical, physiological or enzymatic action after administration, although it does not exhibit physiological activity.

In the present specification, "hydrate" refers to a compound to which water is bound, and is a broad concept including an encapsulated compound having no chemical binding force between water and the compound.

In the present specification, "solvate" refers to a higher order generated between a molecule or ion of a solute and a molecule or ion of a solventA compound.

An aspect of the present invention provides a moisturizing composition comprising 3-O-galloyl-3,3', 5',7-pentahydroxy flavan (3-O-galloyl-3, 3', 5',7-pentahydroxyfla van), an isomer thereof, an acceptable salt thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, a solvate thereof, or a post-fermented tea ketone fraction comprising the same as an active ingredient. The moisturizing includes skin moisturizing.

[ chemical formula 1]

According to one embodiment, the post-fermented tea ketone fraction may be a ketone fraction of a water insoluble extract of post-fermented tea.

According to another specific example, the 3-O-galloyl-3,3', 5',7-pentahydroxy flavan may be Trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan (Trans-3-O-galloyl-3, 3', 5',7-pentahydroxy flavan) represented by the following chemical formula 2. "flavan (flavan)" in the present specification means the above-mentioned 3-O-galloyl-3,3', 5',7-pentahydroxy flavan or trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan.

[ chemical formula 2]

According to another specific example, the ketone fraction may be an alcohol extract of a ketone fraction.

According to another specific example, the above ketone may comprise acetone, carvone (carbovin), pulegone, isolongifolanone (isolongifolanone), 2-heptanone, 2-pentanone, 3-cyclohexanone, 3-heptanone, 4-heptanone, 2-octanone, 3-octanone, 2-nonanone, 3-nonanone, 2-undecanone, 2-tridecanone, methyl isopropyl ketone, ethyl isopentyl ketone, butanolidene acetone, methyl heptenone, dimethyl octenone, geranylacetone, farnesyl acetone, 2, 3-pentanedione, 2, 3-cyclohexanedione, 3, 4-hexanedione, 2, 3-heptanedione, amyl cyclopentanone, 2-cyclopentyl cyclopentanone, hexyl cyclopentanone, 2-n-heptyl cyclopentanone, cis-jasmine, dihydro-jasmine, methyl cyclopentenone2-tert-butylcyclohexanone, p-tert-butylcyclohexanone, 2-sec-butylcyclohexanone, apinone, cryptopinone, p-tert-pentylcyclohexanone, 1- (3, 5, 6-trimethyl-3-cyclohexen-1-yl) ethanone, nerone, 4-cyclohexyl-4-methyl-2-pentanone, ketooxide->Epoxy isophorone>Methylnaphthyl ketone, alpha-methylanisolidene acetone, anisoylacetone, p-methoxyphenylacetone, benzylidene acetone, p-methoxyacetophenone, p-methylacetophenone, propiophenone, acetophenone, alpha-dynacone (Dynascone), ellinone (lritone), ionone (ionone), pseudoionone (Pseudoionone), methyl ionone, methyl elline, 2, 4-di-tert-butylcyclohexanone, allylionone, 2-acetyl-3, 3-dimethylnorbornane, verbenone, fenchonne (fenchon), cyclopentadecanone, cyclohexanonene, and the like, may be contained entirelyAs ketones and their mixtures, which are solvents generally usable in this field, acetone may be preferred.

According to another specific example, the above-mentioned alcohol may be a single alcohol or a mixture which can be generally used in the art, and ethanol may be preferred.

According to another embodiment, the 3-O-galloyl-3,3', 5',7-pentahydroxy flavan or trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan, its isomer, its acceptable salt, its pharmaceutically acceptable salt, its prodrug, its hydrate, or its solvate in the composition may be 0.000001 wt.% or more, 0.000005 wt.% or more, 0.00001 wt.% or more, 0.00005 wt.% or more, 0.0001 wt.% or more, 0.0002 wt.% or more, 0.0005 wt.% or more, 0.001 wt.% or more, 0.005 wt.% or more, 0.01 wt.% or more, 0.05 wt.% or more, 0.1 wt.% or more, 0.3 wt.% or more, 0.5 wt.% or more, 1 wt.% or more, 1.5 wt.% or more, 1.8 wt.% or more, 2.0001 wt.% or more, 2.0002 wt.% or more, 2.0005 wt.% or more, 2.8 wt.% or more, 2.3 wt.% or more, or 5 wt% or less, 4.8 wt% or less, 4.5 wt% or less, 4.2 wt% or less, 3.8 wt% or less, 3.5 wt% or less, 3.2 wt% or less, 3 wt% or less, 2.8 wt% or less, 2.5 wt% or less, 2.2 wt% or less, 2 wt% or less, 1.8 wt% or less, 1.5 wt% or less, 1.2 wt% or less, 1 wt% or less, 0.5 wt% or less, 0.3 wt% or less, 0.1 wt% or less, 0.05 wt% or less, 0.01 wt% or less, 0.005 wt% or less, 0.001 wt% or less, 0.0005 wt% or less, 0.0002 wt% or less, 0.0001 wt% or less, and, 0.00005 wt% or less, 0.00001 wt% or less, or 0.000005 wt% or less. It may be preferably 0.000001 to 5 wt%.

According to another specific example, the content of the post-fermented tea ketone fraction in the composition may be 0.01 wt% or more, 0.1 wt% or more, 1 wt% or more, 5 wt% or more, 10 wt% or more, 15 wt% or more, 20 wt% or more, 25 wt% or more, 30 wt% or more, 35 wt% or more, 40 wt% or more, 45 wt% or more, 50 wt% or more, 55 wt% or more, 60 wt% or more, 65 wt% or more, 70 wt% or more, 75 wt% or more, 80 wt% or more, 85 wt% or more, 90 wt% or more, or 95 wt% or more, based on the total weight of the composition, or 100 wt% or less, 95 wt% or less, 90 wt% or less, 85 wt% or less, 80 wt% or less, 75 wt% or less, 70 wt% or less, 65 wt% or less, 60 wt% or less, 55 wt% or less, 50 wt% or less, 45 wt% or less, 40 wt% or less, 35 wt% or less, 30 wt% or less, 25 wt% or less, 20 wt% or less, 15 wt% or less, 10 wt% or less, 5 wt% or less, 1 wt% or less, 0.1 wt% or less, or 0.05 wt% or less. It may be preferably 0.01 to 100% by weight.

According to another specific example, in the fraction, 3-O-galloyl-3,3', 5',7-pentahydroxy flavan or trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan, an isomer thereof, an acceptable salt thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof may be 0.0001 wt% or more, 0.0002 wt% or more, 0.0005 wt% or more, 0.001 wt% or more, 0.005 wt% or more, 0.01 wt% or more, 0.05 wt% or more, 0.1 wt% or more, 0.5 wt% or more, 1.5 wt% or more, 2 wt% or more, 2.5 wt% or more, 3.5 wt% or more, 4 wt% or less, or 4.5 wt% or less, 4.001 wt% or less, 4.5 wt% or less, 0.05 wt% or less, 0.5 wt% or less, 3.01 wt% or more, 1.5 wt% or less, 2.5 wt% or less, 0.5 wt% or less, 3.5 wt% or more, 2.5 wt% or less, or 2.5 wt% or less, 0.5 wt% or less, 3.5 wt% or more, 3.5 wt% or 3 wt% or 3.5 wt% or more. It may preferably comprise 0.0001 to 5% by weight.

According to another specific example, the 3-O-galloyl-3,3', 5',7-pentahydroxy flavan or trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan, an isomer thereof, an acceptable salt thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof may be administered in an amount of 0.0001 g/kg/day or more, 0.001 g/kg/day or more, 0.01 g/kg/day or more, 0.1 g/kg/day or more, 1 g/kg/day or more, 2 g/kg/day or more, 3 g/kg/day or more, 4 g/kg/day or more, 5 g/kg/day or more, 6 g/kg/day or more, 7 g/kg/day or more, 8 g/kg/day or more, 9 g/kg/day or more, 10 g/kg/day or more, 11 g/kg/day or more, 12 g/day or more, 14 g/day or more, or 15 g/kg/day or less, 14 g/kg/day or less, 13 g/kg/day or less, 12 g/kg/day or less, 11 g/kg/day or less, 10 g/kg/day or less, 9 g/kg/day or less, 8 g/kg/day or less, 7 g/kg/day or less, 6 g/kg/day or less, 5 g/kg/day or less, 4 g/kg/day or less, 3 g/kg/day or less, 2 g/kg/day or less, 1 g/kg/day or less, or less, less than 0.1 g/kg/day, less than 0.01 g/kg/day, less than 0.001 g/kg/day, or less than 0.0005 g/kg/day. It may be preferably 0.0001 g/kg/day to 15 mg/kg/day.

According to another specific example, the moisture retention may be based on any one or more of increasing moisture supply and preventing moisture loss.

According to an embodiment of the present invention, as a result of the moisturizing test using the 3-O-galloyl-3,3', 5',7-pentahydroxy flavan, it was confirmed that the moisture content of the skin was significantly increased when the 3-O-galloyl-3,3', 5',7-pentahydroxy flavan of the present invention was applied to the skin (see Table 1), and thus the above-mentioned substances exhibited excellent moisturizing ability.

The above-described composition according to an aspect of the present invention may be a pharmaceutical composition. The pharmaceutical composition may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, etc. The dosage form for oral administration may be, but is not limited to, tablets, pills, soft and hard capsules, granules, powders, microparticles, liquids, emulsions or pellets. The dosage form for non-oral administration may be, but is not limited to, a solution, suspension, emulsion, gel, injection, drop, suppository, patch, ointment, or spray. The above dosage forms may be easily manufactured according to a method common in the art, and may further comprise surfactants, excipients, hydration agents, emulsification promoters, suspending agents, salts or buffers for adjusting osmotic pressure, colorants, spices, stabilizers, preservatives, or other commonly used auxiliaries.

The applicable amount or administration amount of the above-described composition according to an aspect of the present invention varies according to the age, sex, weight, pathological state and severity thereof of the subject to be administered, the administration route or judgment of prescribing physician. The determination of the applicable amount based on such factors is within the level of those skilled in the art, and the daily administration amount of the active ingredient may be, for example, 0.001. Mu.g/kg/day to 5000 mg/kg/day, more specifically, 0.0001 mg/kg/day to 15 mg/kg/day, but is not limited thereto.

According to another specific example, the composition may be a food composition or a health food composition.

The formulation of the food composition or the health food composition is not particularly limited, and for example, the food composition or the health food composition may be formulated into a tablet, a granule, a pill, a powder, a capsule, a liquid such as a drink, a caramel, a gel, a stick, a tea bag, or the like. The food composition or the health food composition of each dosage form can be formulated by appropriately selecting and blending components commonly used in the field except for the active ingredient, without any difficulty, according to the dosage form or purpose of use, and a synergistic effect may occur when the components are used together with other raw materials.

The above composition can be administered by various methods such as simple ingestion, drinking, injection administration, spray administration or extrusion administration.

In the food composition or the health food composition according to the aspect of the present invention, the amount of the above-mentioned active ingredient to be administered is determined within the level of those skilled in the art, and the amount to be administered per day may be, for example, 0.0001 mg/kg/day to 15 mg/kg/day, but is not limited thereto, and may be varied depending on various factors such as the age, health state, complications and the like of the subject to be administered.

The food composition or health food composition according to one aspect of the present invention may be, for example, various foods such as chewing gum, caramel product, candy, water ice, biscuits, and the like, or beverage products such as soft drinks, mineral water, alcoholic beverages, and the like, and health functional foods including vitamins, minerals, and the like.

In addition to the above, the food composition or health food composition according to an aspect of the present invention may contain various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and thickeners (cheese, chocolate, etc.), pectic acids and salts thereof, alginic acids and salts thereof, organic acids, protective colloid tackifiers, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonating agents for carbonated beverages, and the like. In addition to this, the food composition according to an aspect of the present invention may further comprise pulp for manufacturing natural fruit juice, fruit juice beverage and vegetable beverage. Such components may be used singly or in combination. Although the ratio of such additives is not critical, it is generally within the range of 0 to about 50 parts by weight per 100 parts by weight of the composition according to one aspect of the invention.

According to another specific example, the composition may be a skin external composition. The composition for external application to the skin may be a composition in cosmetics, oral agents, detergents, medicine, pharmacy, etc., but is not limited thereto. The external preparation for skin is not particularly limited in the form of, for example, a skin softening lotion, a skin tightening lotion, a nourishing cream, a massage cream, an essence, an eye cream, an eye essence, a makeup removing cream, a makeup removing foam, a makeup removing lotion, a mask, a powder, a body lotion, a skin oil, a skin beautifying essence, and the like.

In addition, the skin external composition of the present specification may further contain one or more selected from the group consisting of a functional salt (salt) for a specific purpose and a pH adjuster for adjusting pH. In this case, the above-mentioned salt may be selected from inorganic salts, organic salts and/or organic-inorganic salts for ion shielding, moisture retention, ultraviolet blocking and the like. Concrete examples areFor example, the salt may be selected from sodium chloride (NaCl), sodium phosphate (Na ₃ PO ₄ ) And calcium chloride (CaCl) ₂ ) Etc. The pH regulator is selected from acid (aicd) and base (base), and may be selected from hydrochloric acid, sulfuric acid, tartaric acid, citric acid, phosphoric acid, acetic acid, lactic acid, sodium lactate, sodium hydroxide, potassium hydroxide, alkylamine, alkanolamine, aqueous ammonia, and the like.

The skin external composition of the present specification may be a cosmetic, pharmaceutical or medical external composition. The cosmetic, pharmaceutical or pharmaceutical composition for external use may further contain an auxiliary agent such as a preservative, a stabilizer, a hydrating agent or an emulsifying promoter, a salt for regulating osmotic pressure and/or a buffer, and other therapeutically useful substances. The composition can be made into lotion, cream, ointment or gel. The skin external composition is preferably administered transdermally.

The amount of the active ingredient of the above pharmaceutical or pharmaceutical composition for external use varies depending on the age, sex, weight, specific disease or pathological state to be treated, severity of disease or pathological state, administration route and judgment of prescribing physician of the subject to be treated. Determination of the amount of drug administered based on such factors is well within the level of skill in the art. In general, the amount of the active ingredient to be administered may be in the range of 0.0001 mg/kg/day to 15 mg/kg/day, but is not limited thereto.

In one aspect of the present specification, the composition is not particularly limited in terms of formulation, and may be a cosmetic composition. The cosmetic composition may be, for example, a skin and/or hair composition, such as a skin softening lotion, a skin tightening lotion, a nourishing cream, a massage cream, an eye essence, an essence, a makeup removing cream, a makeup removing foam, a makeup removing lotion, a mask, a powder, a body lotion, a skin cream, a skin beautifying essence, a body wash, a hair dye, a shampoo, a conditioner, a hair styling agent, a hair tonic, an ointment, a gel, a cream, a patch, a spray, a skin adhesive type, or the like, but is not limited thereto.

Further, the present invention can be appropriately selected and combined with other components of each dosage form other than the above-described essential components, without any difficulty, according to the kind or purpose of use of the other external preparation.

The above-mentioned composition according to the present specification may be a cosmetic composition, which may be provided in all dosage forms suitable for topical application. For example, the composition may be in the form of a solution, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an aqueous phase in an oil phase, a suspension, a solid, a gel, a powder, a paste, a microneedle, a foam (foam), or an aerosol composition. The composition of such dosage forms may be manufactured according to methods conventional in the art.

The cosmetic composition according to the present specification may contain functional additives and components contained in general cosmetic compositions, in addition to the compounds or fractions of the present specification. As the above functional additives, a component selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymeric peptides, polymeric polysaccharides, sphingolipids and seaweed extracts may be contained. The cosmetic composition according to the present specification may preferably contain other ingredients capable of bringing about synergistic effects on the main effects within a range that does not affect the main effects thereof. In addition, the cosmetic composition according to the present specification may further comprise a humectant, an emollient, a surfactant, an ultraviolet absorber, a preservative, a bactericide, an antioxidant, a pH adjuster, organic and inorganic pigments, a perfume, a coldness feeling agent, or an antiperspirant. The amount of the above-mentioned components to be blended may be from 0.001 to 10% by weight, specifically from 0.01 to 3% by weight, based on the total weight of the composition, within a range not affecting the object and effect of the present specification, and can be easily selected by a person skilled in the art.

The constitution and effect of the present specification will be described more specifically below by way of examples, experimental examples and dosage form examples. However, these examples are provided merely for the purpose of illustration to aid understanding of the present specification, and the scope and range of the present specification are not limited to the following examples.

< example 1> production of post-fermented tea sample

Adding water to green tea prepared from green tea (Camellia sinensis var. Yabukita) leaves to obtain water contentAdjusted to 40 wt%. Where 5X 10 is inoculated ⁶ cfu/g of Bacillus subtilis (Bacillus subtillis) was fermented at 50℃for 3 days and at 80℃for 4 days. The fermented tea is dried with hot air at 70 to 80 ℃ to a moisture content of 4 to 6 wt%, and then cured at 10 ℃ for 100 days.

The cured tea sample was pulverized for 15 seconds and sieved with a stainless steel sieve having a mesh size of 1 mm. Then, 50mg of the powder was added to 1.5ml of an Eppendorf tube (Eppendorf tube), 1ml of deionized water was added, and after stirring at a constant speed in a constant temperature water tank at 60℃for 30 minutes, centrifugation was performed at 13000rpm at 25℃for 15 minutes. Only the water insoluble fraction is separated from the dried fermented green tea extract.

< example 2> fractional distillation and separation of Compounds

150g of the post-fermented tea sample was fractionated with acetone to remove catechin derivatives and caffeine as much as possible, thereby obtaining flavonoid-concentrated soluble substances. For 40g of the above acetone-soluble material, chloroform was purified by silica gel column chromatography: a mixture of methanol was used as a solvent, and elution was performed in the order of 10:1, 5:1, and 1:1 (v/v), to obtain respective fractions.

Here, 12g of chloroform was purified by high performance liquid chromatography (high performance liquid chromatography, HPLC, waters Alliance 2695system, waters, USA): as a result of analysis of the methanol 10:1 (v/v) fraction, caffeine was still present as a main compound in the case where no fractionation was performed with acetone as described above, and removal of caffeine was confirmed after fractionation with acetone as described above (FIG. 1).

8.9g of decaffeinated chloroform was fractionated by high-capacity high performance countercurrent chromatography (high-performance countercurrent chromatography, HPCCC, dynamic Extractions Ltd, UK): methanol 10:1 (v/v) fraction. The solvent used at this time was n-hexane-TBME (methyl tert-butyl ether) -BuOH-MeCN-water (0.25:3:1:1:5, v/v) at a flow rate of 25ml/min. By using the above conditions, a total of 10 subfractions were separated (FIG. 2), and analysis by HPLC confirmed that most of the compounds contained in each fraction were flavonoids (flavonoids) (FIGS. 3 and 4).

Separating Trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan (Trans-3-O-galloyl-3, 3', 5',7-pentahydroxyflavan, C) from the above fraction ₂₂ H ₁₈ O ₁₀ Molecular weight 442.0900), the structure of the isolated compound is as follows.

[ chemical formula 2]

At the position of ¹ In the case of H nuclear magnetic resonance (nuclear magnetic resonance, NMR), methanol-d3 (methanol-d 3) was used as the solvent (solvent), bruker Advance DPX-500 (BRUKER Co., USA) was used as the equipment, and the NMR data of trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan were as follows, and the specific chart is shown in FIG. 5.

¹ H 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 evaluation of skin moisturizing Effect

In order to understand the skin moisturizing effect of the trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan, the trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan was applied to 3 sites of the inner side 3X3 square of the lower arm of 14 healthy men and women (7 men and 7 women) who were 20 to 30 years old.

Specifically, as a test substance, the above-mentioned trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan was diluted at a concentration of 0.2%, and as a positive control, glycerin was used at a concentration of 5%. In the initial stage of the test substance, the skin moisture amount after 2 days, after 7 days, and after 11 days was measured by the following method using a skin moisture tester (Corneometer CM825 (courage+ Khazaka electronic GmbH, germany)).

The principle of measurement of the skin moisture tester is to measure the moisture retention by measuring the ionic degree of moisture in the epidermis of the skin by an electrical method and calculating the moisture amount by digitizing the ionic degree of moisture. First, a probe (probe) of a skin moisture tester is placed on a skin site to be measured. When the skin is pressed by the probe, the conductivity of the skin is digitized by the sensor and is displayed on the screen, and the measurement is repeated 3 times at each site to obtain an average value. The results are shown in table 1 below.

TABLE 1

From the above table, it was confirmed that when trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan was applied to the skin, the skin moisture content showed a statistically significant tendency to increase (paired T-test, p < 0.01), and the skin moisture content was maintained after 11 days of application. Therefore, it is found that the composition containing trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan according to the present specification effectively retains moisture of skin after application and is excellent in skin moisturizing ability.

Soft capsule of formulation example 1

A soft capsule fill was prepared by mixing 150mg of post-fermented tea acetone fraction, 440mg of lactose, 430mg of corn starch and 2mg of magnesium stearate according to example 2 of the present specification. In addition, a soft capsule shell was produced at a ratio of 66 parts by weight of gelatin, 24 parts by weight of glycerin and 10 parts by weight of sorbitol solution, and the filling solution was filled, unlike the above steps, to produce a soft capsule.

In addition, the trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan 3mg, lactose 440mg, corn starch 450mg and magnesium stearate 2mg according to the examples of the present specification were mixed to produce a soft capsule filling liquid. Then, soft capsule shells were produced by the above method, and the filling liquid was filled, thereby producing soft capsules.

< dosage form example 2> tablet

The post-fermented tea acetone fraction according to example 2 of the present specification was mixed with 150mg, 15mg of vitamin E, 15mg of vitamin C, 250mg of galactooligosaccharides, 60mg of lactose and 140mg of maltose, and after granulation using a fluidized bed dryer, 8mg of sugar ester (sucrose ester) was added. The composition was tableted by a usual method to produce tablets.

In addition, 3mg of trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan, 15mg of vitamin E, 15mg of vitamin C, 259mg of galacto-oligosaccharide, 60mg of lactose and 140mg of maltose in the examples were mixed and granulated by a fluidized bed dryer, and 8mg of sugar ester (sugamster) was added. Tablets are produced by tabletting the composition by a conventional method.

< dosage form example 3> beverage

After 80mg of post-fermented tea acetone fraction, 9mg of vitamin E, 9mg of vitamin C, 10g of glucose, 0.6g of citric acid, and 25g of liquid oligosaccharide according to example 2 of the present specification were mixed, 400ml of purified water was added to fill. After filling into bottles, the bottles were sterilized at 30℃for 4 to 5 seconds to prepare drinks.

Further, 0.1mg of trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan, 9mg of vitamin E, 9mg of vitamin C, 10g of glucose, 0.6g of citric acid and 25g of liquid oligosaccharide of example were mixed, and then 400ml of purified water was added thereto to fill each bottle in 200 ml. After filling into bottles, the bottles were sterilized at 30℃for 4 to 5 seconds to prepare drinks.

< formulation example 4> granule

The post-fermented tea acetone fraction according to example 2 of the present specification was mixed with 150mg, vitamin E9 mg, vitamin C9 mg, anhydrous crystalline glucose 250mg and starch 550mg, and after being formed into granules using a fluidized bed granulator, the granules were packed into bags to produce granules.

In addition, 3mg of trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan, 9mg of vitamin E, 9mg of vitamin C, 250mg of anhydrous crystalline glucose and 550mg of starch in the examples were mixed, and the mixture was formed into granules by a fluidized bed granulator, and then filled into bags to prepare granules.

< formulation example 5> injection

Injection formulations were prepared by a conventional method according to the compositions shown in Table 2 below.

TABLE 2

Compounding ingredients	Content of
		Post-fermented tea acetone fraction according to example 2	100mg
Sterilized distilled water for injection	Proper amount of
		PH regulator	Proper amount of

In addition, 3mg of trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan of the example was used in place of the above post-fermented tea acetone fraction to prepare an injection.

< formulation example 6> health food

Health foods were produced by a conventional method according to the compositions shown in Table 3 below.

TABLE 3

In addition, 3mg of trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan of the example was used instead of the above post-fermented tea acetone fraction, thereby producing a health food.

The composition ratio of the above-mentioned vitamin and inorganic substance mixture is mixed by taking a component relatively suitable for health foods as an example, but the mixing ratio may be arbitrarily modified, and the above-mentioned components are mixed according to a conventional health food production method and then used in the production of a health food composition according to a conventional method.

< formulation example 7> health drink

TABLE 4

Composition of the components	Content of
		Post-fermented tea acetone fraction according to example 2	50mg
Citric acid	1000mg
		Oligosaccharide	100g
Concentrated plum juice	2g
		Taurine	1g
Purified water	Allowance of
		Total volume of	900ml

As shown in table 4 above, the total volume was set to 900ml by adding the remaining amount of purified water, mixing the above ingredients according to a conventional method for producing a healthy beverage, stirring and heating at 85 ℃ for about 1 hour, filtering the resulting solution, placing the solution in a sterilized 2 liter container, sealing and sterilizing, and then refrigerating and preserving the solution to produce a healthy beverage.

In addition, 0.1mg of trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan of the example was used instead of the above post-fermented tea acetone fraction, thereby producing a healthy beverage.

< formulation example 8> skin softening lotion (skin lotion)

A smoothing toner (emollient lotion) was prepared from 3% by weight of post-fermented tea acetone fraction, 1.00% by weight of magnesium salt of L-ascorbic acid-2-phosphate, 1.00% by weight of water-soluble collagen (1% aqueous solution), 0.10% by weight of sodium citrate, 0.05% by weight of citric acid, 0.20% by weight of licorice extract, 3.00% by weight of 1, 3-butanediol, and the balance purified water according to example 2.

In addition, 0.1% by weight of trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan of the example was used instead of the above post-fermented tea acetone fraction, thereby producing a smoothing toner.

< formulation example 9> cream formulation

A cream formulation was prepared using 3.00 wt% post-fermented tea acetone fraction according to example 2, 2.00 wt% polyethylene glycol monostearate, 5.00 wt% self-emulsifying glycerin monostearate, 4.00 wt% propylene glycol, 6.00 wt% squalene, 6.00 wt% tri-2-ethyl hexane glyceride, 1.00 wt% glycosphingolipid, 7.00 wt% 1, 3-butylene glycol, 5.00 wt% beeswax, and the balance purified water.

In addition, the trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan of example was used in place of the above post-fermented tea acetone fraction at an O.1 wt% to produce a cream formulation.

< dosage form 10> mask

A mask was manufactured using 3.00 wt% post-fermented tea acetone fraction according to example 2, 13.00 wt% polyvinyl alcohol, 1.00 wt% L-ascorbic acid-2-magnesium phosphate salt, 1.00 wt% lauroyl hydroxyproline, 2.00 wt% water-soluble collagen (1% aqueous solution), 3.00 wt% 1, 3-butylene glycol, 5.00 wt% ethanol, and the balance purified water.

In addition, the above post-fermented tea acetone fraction was replaced with 0.1% by weight of trans-3-O-galloyl-3,3', 5',7-pentahydroxyflavan of example, thereby producing a mask.

While specific portions of the present specification have been described in detail, it will be apparent to those skilled in the art that such specific techniques are merely preferred embodiments, and that the scope of the present specification is not limited thereto. Accordingly, the substantial scope of the present description is defined based on the appended claims and equivalents thereof.

Claims

1. Use of 3-O-galloyl-3,3', 5',7-pentahydroxy flavan represented by the following chemical formula 1, an acceptable salt thereof, or a post-fermented tea ketone fraction comprising the same in the manufacture of a moisturizing composition in which the content of 3-O-galloyl-3,3', 5',7-pentahydroxy flavan or an acceptable salt thereof is 0.000001 wt% to 5 wt% relative to the total weight of the composition,

chemical formula 1

2. The use according to claim 1, wherein the post-fermented tea ketone fraction is a ketone fraction of a non-water soluble extract of post-fermented tea.

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

4. The use according to claim 1, wherein the 3-O-galloyl-3,3', 5',7-pentahydroxy flavan is trans-3-O-galloyl-3,3', 5',7-pentahydroxy flavan represented by the following chemical formula 2,

chemical formula 2

5. Use according to claim 1, wherein the content of post-fermented tea ketone fraction in the composition is 0.01 to 100 wt% relative to the total weight of the composition.

6. The use of claim 1 wherein the 3-O-galloyl-3,3', 5',7-pentahydroxy flavan or acceptable salt thereof comprises from 0.0001 wt.% to 5 wt.% based on the total weight of the fraction in the fraction.

7. The use of claim 1, wherein the 3-O-galloyl-3,3', 5',7-pentahydroxyflavan or acceptable salt thereof is administered in an amount of 0.0001 mg/kg/day to 15 mg/kg/day.

8. Use according to any one of claims 1 to 7, wherein the composition is a pharmaceutical composition.

9. Use according to any one of claims 1 to 7, wherein the composition is a cosmetic composition.