JP2019520786A - Moisturizing composition containing 3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone - Google Patents

Abstract

In one aspect, the present specification relates to a moisturizing composition containing a post-fermented tea ketone fraction as an active ingredient. In another aspect, the present specification relates to 3-O-galloyl-3 separated from the post-fermented tea ketone fraction, 3 ′, 5,5 ′, 7-pentahydroxyflavone (3-O-galloyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavan), its isomer, its acceptable salt, its prodrug, its With respect to a moisturizing composition containing a hydrate or a solvate thereof as an active ingredient, the present specification can be utilized in various fields related to skin moisturizing. [Selection] Figure 5

Description

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

  Human skin performs a barrier function that protects an individual from the outside. The barrier function refers to protection against various external stimuli (chemicals, air pollutants, dry environment, ultraviolet light, etc.) and a protective function to suppress excessive release of body water through the skin. The protective function can only retain its function when the stratum corneum composed of keratinocytes is normally formed. The stratum corneum (Stratum corneum, horny layer) present in the outermost layer of the epidermis is formed of keratinocytes and is composed of keratinocytes that have completely differentiated and a lipid layer surrounding them (Non-patent Document 1). The stratum corneum has firmness and flexibility by forming the stratum corneum while keratinocytes form natural moisturizing factor (NMF) and intercellular fat (ceramide, cholesterol, fatty acid) during the keratinization process. To act as a skin barrier.

  Such stratum corneum functions due to lifestyle factors such as excessive face washing and bathing, environmental factors such as dry air pollutants, and intrinsic diseases such as atopic skin and senile skin. In fact, due to a variety of factors that have been introduced today, cases of skin dryness symptoms and their resulting disorders are increasing.

  Various studies have been conducted to supply fluid from the outside in order to retain appropriate skin moisture and to prevent fluid loss from the body, and in fact, various moisturizers capable of retaining water. (Moisturizer) has been developed. However, despite the increasing need for the development of natural product-derived moisturizers, with increasing concern about the harmfulness of chemicals, research and development of such natural product-derived moisturizers The fact is that it is not enough yet.

U.S. Patent No. 9061023 International Publication No. 2016/093515 International Publication No. 2015/053460 gazette Korean Published Patent No. 10-2012-0021709 Korean Registered Patent No. 10-1222677

C. L. Marcelo, P. S. Tong, Epidermal keratinocyte growth: changes in protein composition and synthesis of keratins in differentiating cultures, J Invest Dermatol, 80 (1983), pp. 37-44

  The present invention, in one aspect, relates to moisturizing substances derived from natural products, and it is an object of the present invention to provide a moisturizing composition comprising a post-fermented tea fraction.

  In another aspect, the present invention relates to 3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone (3-O-galloyl-3,3 'isolated from post-fermented tea fractions. It is an object of the present invention to provide a moisturizing composition containing (5, 5, 5 ', 7-pentahydroxyflavan) as an active ingredient.

  MEANS FOR SOLVING THE PROBLEMS In order to solve the above problems, the present invention provides, in one aspect, 3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone (3-O-garyl-3,3 ', 5 , 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 containing it as an active ingredient Provided is a moisturizing composition.

  In another aspect, the present invention provides 3-O-galloyl-3,3 ', 5,5', 7-pentahydroxyflavone (3-O-garyl-3,3 ', 5,5', 7-pentahydroxyflavan Skin moisturization comprising administering the individual as an active ingredient, its isomer, its acceptable salt, its prodrug, its hydrate, its solvate, or a post-fermented tea ketone fraction containing it as an active ingredient Provide a way.

  The present invention also provides, in another aspect, 3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone (3-O-gallyl-3) for use in the preparation of a composition for moisturizing skin. , 3 ', 5,5', 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 containing it Provide a use.

  In another aspect of the present invention, 3-O-galloyl-3,3 ', 5,5', 7-pentahydroxyflavone (3-O-galloyl-3,3) is used as an active ingredient for skin moisturizing. ', 5,5', 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 containing the same .

  In another aspect, the present invention provides 3-O-galloyl-3,3 ', 5,5', 7-pentahydroxyflavone (3-O-galloyl-3, 3) as an active ingredient for moisturizing the skin. 3 ', 5,5', 7-pentahydroxyflavan), an isomer thereof, an acceptable salt thereof, a prodrug thereof, a hydrate thereof, a solvate thereof, or a non-fermented tea ketone fraction containing it Provide therapeutic cosmetic use.

  The present invention provides, in one aspect, a composition comprising a post-fermented tea ketone fraction and a composition comprising a specific compound, which can be widely utilized in the moisturizing related field.

It is the result of analyzing a post-fermented tea extract by high performance liquid chromatography, and shows the case of passing an acetone fraction and the case of not passing an acetone fraction. The caffeine-removed chloroform: methanol 10: 1 (v / v) fraction was separated into 10 lower fractions using high-performance countercurrent chromatography (HPCCC) It shows that. It is shown for the fractions 1 to 5 of the 10 lower fractions fractionated using HPCCC. Of the 10 lower fractions fractionated using HPCCC, it is shown for fractions 6 to 10. 1 shows a nuclear magnetic resonance (NMR) graph of Trans-3-O-galloyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone.

  Hereinafter, the present specification will be described in detail.

  As used herein, "post-fermented tea" includes those fermented by additional microorganisms or substances that are not enzymes present in the tea leaves.

  In the present specification, the "ketone fraction" is a fraction of a specific substance or an extract fractionated or fractionated using a ketone solvent, and a fraction thereof which is extracted again with a particular solvent. including. The type of the ketone is not limited, but acetone is preferred, and the fractionation method and extraction method may be any method known to those skilled in the art.

  As used herein, “isomers” are especially optical isomers (eg essentially pure enantiomers, essentially pure diastereomers or these Mixtures of) as well as conformational isomers (ie, isomers that differ only in their angle of one or more chemical bonds), positional isomers (especially tautomers) Or geometric isomers (eg, cis-trans isomers).

  In the present specification, the term "essentially pure" means, for example, a specific compound which can be mentioned as an enantiomer or a diastereomer when used in connection with an enantiomer or a diastereomer, for example. Is 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, most preferably about 99.5% or more w / w) means to exist.

  As used herein, "acceptable" may be used on animals, more particularly humans, by avoiding considerable toxicity when used in normal or pharmaceutical dosages (dosage) Can be approved by the government or a similar regulatory mechanism, or approved, or listed in a food code, a health functional food code, or a general pharmacopoeia, or any other general Means to be recognized as being described in the

  As used herein, "acceptable salt" means a salt according to one aspect of the present invention which is normally or pharmaceutically acceptable and which has the preferred activity of the parent compound. The salt is formed of an inorganic acid such as (1) hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid or the like; or acetic acid, propionic acid, hexanoic acid, cyclopentene propionic 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-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo [2,2 , 2] -oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, tri Acid addition salt formed by an organic acid such as tyl acetate, tert-butyl acetate, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid; or (2) parent compound It may include salts formed when the acidic protons present are replaced.

  As used herein, "prodrug" refers to a drug whose chemical and physical properties have been modulated by chemically changing a substance, which itself does not exhibit physiological activity, but administration It can later be turned into an original drug and exert its medicinal effects by the action of a chemical, physiological or enzyme in the body.

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

  As used herein, "solvate" refers to a higher-order compound generated between molecules or ions of a solute and molecules or ions of a solvent.

  The present invention relates, in one aspect, to 3-O-galloyl-3,3 ', 5,5', 7-pentahydroxyflavone (3-O-garyl-3,3 ', 5, represented by the following chemical formula 1 5 ', 7-pentahydroxyflavan), 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 containing it There is provided a moisturizing composition comprising an image as an active ingredient. The moisturizing includes skin moisturizing.

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

  According to another embodiment, the 3-O-galoyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone is a compound represented by Formula 2 below: Trans-3-O-galoyl-3,3 ', 5,5', 7-Pentahydroxyflavone (Trans-3-O-garyl-3,3 ', 5,5', 7-pentahydroxyflavan). In the present specification, "flavan" is the above 3-O-galloyl-3,3 ', 5,5', 7-pentahydroxyflavone or Trans-3-O-galloyl-3,3 ', 5,5' , 7-pentahydroxy flavone.

  According to another embodiment, the ketone fraction may be an alcohol extract of the ketone fraction.

  According to another embodiment, the ketone is acetone, carbon (carvon), pulegone, isolongifolnone, 2-heptanone, 2-pentanone, 3-hexanone, 3-heptanone, 4-heptanone, 2 -Octanone, 3-octanone, 2-nonanone, 3-nonanone, 2-undecanone, 2-tridecanone, methyl isopropyl ketone, ethyl isoamyl ketone, butylidene acetone, methyl heptenone, dimethyl octenone, geranyl acetone, farnesyl acetone, 2, 3 -Pentadione, 2,3-hexadione, 3,4-hexadione, 2,3-heptadione, amyl cyclopentanone, amyl cyclopentenone, 2-cyclopentyl cyclopentanone, hexyl cyclope Tanone, 2-n-heptylcyclopentanone, cis-jasmone, dihydrojasmone, methylcorrion, 2-tert-butylcyclohexanone, p-tert-butylcyclohexanone, 2-sec-butylcyclohexanone, celery ketone, krypton, p-tert-pentyl Cyclohexanone, methylcyclocitron, nerone, 4-cyclohexyl-4-methyl-2-pentanone, oxide ketone, emoxyflone, methylnaphthyl ketone, α-methylanisulacetone, anicylacetone, p-methoxyphenylacetone, benzylideneacetone, p -Methoxyacetophenone, p-methylacetophenone, propiophenone, acetophenone, α-dynascon (Dynascone), iritone (lritone), Nonionone, Pseudoionone (Pseudoionone), Methylionone, Methyliritone, 2,4-Di-tert-Butylcyclohexanone, Allylionone, 2-Acetyl-3,3-di-methyl norbornane, Verbenone, Fenchon, Cyclo It may contain pentadecanone, cyclohexadecenone and the like, and may contain any of ketones and their mixtures as solvents which can be generally used in the art, preferably acetone.

  According to another embodiment, the alcohol may be a single or a mixture of alcohols generally used in the art, preferably ethanol.

  According to another embodiment, 3-O-galloyl-3,3 ', 5,5', 7-pentahydroxyflavone or Trans-3-O-galloyl-3,5,5 in said composition 5 ', 7-pentahydroxyflavone, an isomer thereof, an acceptable salt thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof, wherein the total mass of the composition is 0.000001 mass% or more, 0.000005 mass% or more, 0.00001 mass% or more, 0.00005 mass% or more, 0.0001 mass% or more, 0.0002 mass% or more, 0.0005 mass% based on the Or more, 0.001 mass% or more, 0.005 mass% or more, 0.01 mass% or more, 0.05 mass% or more, 0.1 mass% or more, 0.3 mass% or more, 0.5 mass% or more 1% by mass or more, 1.5% by mass or more .8 mass% or more, 2 mass% or more, 2.2 mass% or more, 2.5 mass% or more, 2.8 mass% or more, 3 mass% or more, 3.2 mass% or more, 3.5 mass% or more 3.8 mass% or more, 4 mass% or more, 4.2 mass% or more, 4.5 mass% or more, 4.8 mass% or more, 5 mass% or less, 4.8 mass% or less, 4.5 mass% or less, 4.2 mass% or less, 3.8 mass% or less, 3.5 mass% or less, 3.2 mass% or less, 3 mass% or less, 2.8 mass% or less, 2.5 Mass% or less, 2.2% by mass or less, 2% by mass or less, 1.8% by mass or less, 1.5% by mass or less, 1.2% by mass or less, 1% by mass or less, 0.5% by mass or less, 0 .3 mass% or less, 0.1 mass% or less, 0.05 mass% or less, 0.01 mass% or less, 0.005 mass% or less, 0.001 mass% or less, 0.0005 mass% or less 0.0002 wt% or less, 0.0001% or less, 0.00005 wt% or less, 0.00001% by weight or less, or 0.000005 may be less by mass%. Preferably, it may be 0.000001 to 5% by mass or less.

  According to another embodiment, the content of the post-fermented tea ketone fraction in the composition is 0.01% by mass or more, 0.1% by mass or more, 1% by mass, based on the total mass of the composition. More than, 5 mass% or more, 10 mass% or more, 15 mass% or more, 20 mass% or more, 25 mass% or more, 30 mass% or more, 35 mass% or more, 40 mass% or more, 45 mass% or more, 50 mass% or more Or more, 55 mass% or more, 60 mass% or more, 65 mass% or more, 70 mass% or more, 75 mass% or more, 80 mass% or more, 85 mass% or more, 90 mass% or more, or 95 mass% or more 100% by mass or less, 95% by mass or less, 90% by mass or less, 85% by mass or less, 80% by mass or less, 75% by mass or less, 70% by mass or less, 65% by mass or less, 60% by mass or less, 55% by mass or less 50% by mass or less 45% by mass or less 40% by mass or less 5 mass% or less, 30 mass% or less, 25 mass% or less, 20 mass% or less, 15 mass% or less, 10 mass% or less, 5 mass% or less, 1 mass% or less, 0.1 mass% or less, or 0. It may be 05% by mass or less. Preferably, it may be 0.01% by mass to 100% by mass.

  According to another embodiment, said fraction is 3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone or Trans-3-O-galloyl-3,3'5 , 5 ', 7-pentahydroxyflavone, an isomer thereof, an acceptable salt thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof, wherein the total fraction is 0.0001 mass% or more, 0.0002 mass% or more, 0.0005 mass% or more, 0.001 mass% or more, 0.005 mass% or more, 0.01 mass% or more, 0.05 mass% based on the mass % Or more, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, 1.5% by mass or more, 2% by mass or more, 2.5% by mass or more, 3% by mass or more, 3.5% by mass % Or more, 4% by mass or more, or 4.5% by mass or more, 5% by mass or less, 4.5 quality % Or less, 4% by mass or less, 3.5% by mass or less, 3% by mass or less, 2.5% by mass or less, 2% by mass or less, 1.5% by mass or less, 1% by mass or less, 0.5% by mass or less 0.1 mass% or less, 0.05 mass% or less, 0.01 mass% or less, 0.005 mass% or less, 0.001 mass% or less, 0.0005 mass% or less, or 0.0002 mass% or less It may be. Preferably, 0.0001 mass% to 5 mass% may be contained.

  According to another embodiment, said 3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone or Trans-3-O-galoyl-3,3 ', 5,5', 7 -The dose of pentahydroxyflavone, an isomer thereof, an acceptable salt thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a hydrate thereof, or a solvate thereof, is 0.0001 g / kg / day More than 0.001 g / kg / day, more than 0.01 g / kg / day, more than 0.1 g / kg / day, more than 1 g / kg / day, more than 2 g / kg / day, more than 3 g / kg / day, 4 g / kg / day, 5 g / kg / day, 6 g / kg / day, 7 g / kg / day, 8 g / kg / day, 9 g / kg / day, 10 g / kg / day, 11 g / Kg / day or more, 12 g / kg / day or more, 13 g / kg / day or more, or 14 g / kg / day or more, 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 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, 0.1 g / kg / day or less, 0.01 g / kg / day or less, 0.001 g / kg / day or less, or 0.0005 g / kg / day It may be the following. Preferably, it may be 0.0001 g / kg / day to 15 mg / kg / day.

  According to another embodiment, the moisturizing may be by one or more of water supply increase and water loss prevention.

  As a result of carrying out a moisturizing experiment using the 3-O-galloyl-3,3 ', 5,5', 7-pentahydroxyflavone according to an embodiment of the present invention, the 3-O-galoyl- of the present invention is obtained. When 3,3 ', 5,5', 7-pentahydroxyflavone is applied to the skin, it can be clearly confirmed that the skin water content has significantly increased (see Table 1), which indicates that Was found to exert excellent moisturizing power.

  The composition according to one aspect of the present invention may be a pharmaceutical composition. The pharmaceutical composition may be administered orally, parenterally, rectally, topically, percutaneously, intravenously, intramuscularly, intraperitoneally, subcutaneously and the like. The dosage form for oral administration may be, but is not limited to, tablets, pills, soft and hard capsules, granules, powders, fine granules, solutions, emulsions or pellets . Dosage forms for parenteral administration may be, but are not limited to, solutions, suspensions, emulsions, gels, drops, suppositories, patches or sprays. The dosage form may be easily manufactured by a method usual in the field, and may be a surfactant, an excipient, a wettable, an emulsion promoter, a suspension, a salt or buffer for regulating the osmotic pressure. Colorants, spices, stabilizers, preservatives, preservatives or other customary auxiliaries may further be included.

  The applied amount or dose of the composition according to one aspect of the present invention may vary depending on the age, sex, body weight, pathological condition and severity of the subject to be administered, the route of administration or the judgment of the prescriber. The determination of the applied dose based on such factors is within the level of those skilled in the art, and the daily dose of the active ingredient is, for example, 0.001 μg / 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 embodiment, the composition may be a food composition or a health food composition.

  The dosage form of the food composition or health food composition is not particularly limited. For example, tablets, granules, pills, powders, capsules, liquids such as drinks, caramel, gels, bars, tea bags And the like. The food composition or health food composition of each dosage form may be appropriately selected and formulated by the person skilled in the art according to the dosage form or purpose of use, in addition to the active ingredient, according to the dosage form or purpose of use. Synergistic effects can be achieved when applied simultaneously with other ingredients.

  The composition may be administered in various ways, such as simple ingestion, drinking, injection, spray or squeeze administration.

  In the food composition or health food composition according to one aspect of the present invention, the determination of the dose of the active ingredient is within the level of those skilled in the art, and the daily dose thereof is, for example, 0.0001 mg / kg / day The concentration may be, but is not limited to, -15 mg / kg / day, and may vary depending on various factors such as the age, health condition, and complications of the subject that one wishes to administer.

  The food composition or health food composition according to one aspect of the present invention is, for example, various foods such as chewing gum, caramel products, candies, frozen desserts, confectionery and the like, beverages such as soft drinks, mineral water and alcoholic beverages It may be a health functional food including products, vitamins and minerals.

  In addition to the above, the food composition or health food composition according to one aspect of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers. (Cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonated for carbonated beverages It may contain an agent and the like. In addition, the food composition according to one aspect of the present invention may include natural fruit juices and fruit juice beverages, and pulp for the production of vegetable beverages. These components may be used independently or in combination. The proportion of these additives is not particularly important, but is generally comprised in the range of 0 to about 50 parts by weight per 100 parts by weight of the composition according to one aspect of the present invention.

  According to another embodiment, the composition may be a skin external composition. The composition for external use on the skin may be, but is not limited to, a composition such as a cosmetic, an oral agent, a cleansing agent, medicine and pharmacy. The external preparation for skin is not particularly limited in its dosage form, and for example, soft lotion, astringent lotion, nourishing lotion, nutritional cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing It may be formulated into cosmetics such as foam, cleansing water, pack, powder, body lotion, body cream, body oil and body essence.

In addition, the skin external preparation composition according to the present invention may further contain one or more selected from functional salt for special purpose and pH adjuster for pH control. At this time, the salt may be selected from inorganic salts, organic salts and / or organic / inorganic salts for ion shielding, moisturizing, ultraviolet shielding and the like. Specifically, the salt may be selected from sodium chloride (NaCl), sodium phosphate (Na ₃ PO ₄ ), calcium chloride (CaCl ₂ ) and the like. The pH adjuster is selected from an acid (aicd) and a base (base). For example, hydrochloric acid, sulfuric acid, tartaric acid, citric acid, phosphoric acid, acetic acid, lactic acid, sodium lactate, sodium hydroxide, sodium hydroxide, potassium hydroxide, alkylamine It may be selected from the group consisting of alkanolamines, ammonia and the like.

  The skin external preparation composition according to the present invention may be a cosmetic, pharmaceutical or non-pharmaceutical composition. The cosmetic, pharmaceutical or non-pharmaceutical composition comprises a preservative, a stabilizer, a wettable powder or an emulsion promoter, an adjuvant such as a salt and / or a buffer for regulating the osmotic pressure, and the like, It may further contain a therapeutically useful substance. The composition may be formulated as a lotion, a cream, an ointment or a gel. The external skin composition is preferably administered transdermally.

  The dosage of the active ingredient of the pharmaceutical or non-pharmaceutical composition is the age, sex and weight of the subject to be treated, the particular disease or pathological condition to be treated, the severity of the disease or pathological condition, the route of administration and It may change at the discretion of the prescriber. Determination of dosage based on these factors is within the level of ordinary skill in the art. In general, the dose of the active ingredient 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 formulation, but may be a cosmetic composition. The cosmetic composition is, for example, a composition for the skin and / or the hair, and for example, soft lotion, astringent lotion, nutritive lotion, nutritional cream, massage cream, eye cream, eye essence, essence, Cleansing Cream, Cleansing Lotion, Cleansing Foam, Cleansing Water, Pack, Powder, Body Lotion, Body Cream, Body Essence, Body Wash, Hair Dye, Shampoo, Rinse, Hair Stabilizer, Hair Stabilizer, Ointment, Gel, Cream, Patch, It may have a dosage form such as a spray and a skin adhesion type, but is not limited thereto.

  Further, in each dosage form, in addition to the above-mentioned essential components, other components may be appropriately selected and blended without difficulty according to the type or purpose of use of the other external preparation.

  The composition according to the present invention may be a cosmetic composition, and the cosmetic composition may be provided in any dosage form suitable for topical application. For example, solution, emulsion obtained by dispersing oil phase in aqueous phase, emulsion obtained by dispersing aqueous phase in oil phase, suspension, solid, gel, powder, paste, microneedle, foam or It may be provided in the form of an aerosol composition. The compositions of these dosage forms may be manufactured in a manner conventional in the art.

  The cosmetic composition according to the present specification may further contain functional additives and components contained in a general cosmetic composition, in addition to the compound or fraction of the present specification. The functional additive may include a component selected from the group consisting of a water-soluble vitamin, an oil-soluble vitamin, a high molecular weight peptide, a high molecular weight polysaccharide, a sphingolipid and a seaweed extract. The cosmetic composition according to the present invention may preferably contain other components capable of providing a synergetic effect on the main effect, as long as the main effect is not impaired. In addition, the cosmetic composition according to the present invention includes a moisturizer, an emollient, a surfactant, an ultraviolet light absorber, an antiseptic, a bactericidal agent, an antioxidant, a pH adjuster, an organic and inorganic pigment, a fragrance, and a cool feeling. It may further contain an agent or an antiperspirant. The blending amounts of these components can be easily selected by those skilled in the art within the range that does not impair the purpose and effects of the present specification, and the blending amounts thereof are 0.001 to 10 based on the total mass of the composition. It may be mass%, specifically 0.01 to 3 mass%.

  Hereinafter, the configuration and effects of the present specification will be more specifically described by way of examples, experimental examples, and dosage form examples. Note that these examples are merely illustrated for the purpose of assisting understanding of the present specification, and the scope and scope of the present specification are not limited by the following examples.

<Example 1> Preparation of post-fermented tea sample Water was added to green tea made of green tea (Camellia sinensis var. Yabukita) leaves to adjust the water content to 40% by mass. This was inoculated with 5 × 10 ⁶ cfu / g of Bacillus subtilis and fermented at 50 ° C. for 3 days and then fermented at 80 ° C. for 4 days. The fermented tea was dried to a moisture content of 4% by mass to 6% by mass with hot air at 70 ° C to 80 ° C, and then aged at 10 ° C for 100 days.

  The aged tea sample was ground for 15 seconds and passed through a stainless steel sieve of 1 mm mesh size. Next, 50 mg of crushed is put into a 1.5 ml Eppendorf tube, 1 ml of deionized water is added and stirred at constant temperature for 30 minutes in a 60 ° C. constant temperature water bath, then at 13,000 rpm at 25 ° C. Centrifuge for 15 minutes. Only the portion insoluble in water was separated from the dried fermented green tea extract.

<Example 2> Acquisition of fraction and separation of compound The above-mentioned post-fermented tea sample of 150 g was fractionated with acetone to remove as much as possible the catechin derivative and caffeine, and the soluble matter enriched in flavonoid was obtained. A mixture of chloroform: methanol was used as a solvent to elute sequentially 10: 1, 5: 1, 1: 1 (v / v) to 40 g of the acetone solubles, using a silica gel column chromatography as a primary Each fraction was obtained.

  Here, as a result of analyzing 12 g of chloroform: methanol 10: 1 (v / v) fraction by high performance liquid chromatography (HPLC, Waters Alliance 2695 system, Waters, USA), acetone is used as described above. If not fractionated, caffeine was still present as the main compound, and it was confirmed that caffeine was removed after fractionation using acetone as described above (FIG. 1).

  Using high-performance countercurrent chromatography (HPCCC, Dynamic Extractions Ltd, UK), high-performance countercurrent chromatography (HPCCC) with 8.9 g of chloroform: methanol 10: 1 (v / v) fractions from which caffeine has been removed I fractionated. The solvent used at this time is n-hexane-TBME (Methyl tert-butyl ether) -BuOH-MeCN-Water (0.25: 3: 1: 1: 5, v / v), and the flow rate is 25 ml / min. Met. Using the above conditions, a total of 10 lower fractions were separated (Figure 2) and analyzed by HPLC to confirm that the majority of the compounds contained in each fraction were flavonoid-based ( Figure 3, Figure 4).

From the above fraction, Trans-3-O-galloyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone (Trans-3-O-gallyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavan , C ₂₂ H ₁₈ O ₁₀ , molecular weight 442.0900), and the structure of the separated compound is as follows.

^{In the case of 1} H nuclear magnetic resonance (NMR), methanol-d3 is used as a solvent (solvent), the instrument is Bruker Advance DPX-500 (BRUKER, USA), Trans-3-O-Garoyl The NMR data of −3,3 ′, 5,5 ′, 7-pentahydroxyflavone are as follows, and a specific graph is as shown in FIG.

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

<Experimental Example 1> Evaluation of the skin moisturizing effect In order to examine the skin moisturizing effect of the above Trans-3-O-galloyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone, healthy 20-30s For 14 adult males and females (7 males, 7 females), said Trans-3-O-Galloyl-3,3 ', 5,5', 7-Pentahydroxyflavone is 3 x 3 cm on the inner side of the lower arm. The solution was applied to three sites of a square.

  Specifically, the Trans-3-O-galloyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone as a test substance is diluted to a concentration of 0.2% and glycerol 5 is used as a positive control group. % Was used. The skin moisture content of the test substance was measured with a corneometer (Corneometer CM 825 (Courage + Khazaka electronic GmbH, Germany)) according to the following method in the initial stage, 2 days after, 7 days after and 11 days after.

  The measurement principle of the corneometer is to measure the amount of water present in the epidermis of the skin using an electrical method and measure the moisture level by quantifying the ion degree of the water and quantifying the amount of water. is there. First, a corneometer probe is placed on the skin site to be measured. When the skin was pressed with the probe, the electrical conductivity of the skin was quantified through the sensor and displayed on the screen, and measurement was repeated three times at each site to obtain the average value. The results are shown in Table 1 below.

  As can be confirmed from the above table, when Trans-3-O-galloyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone is applied to the skin, the skin moisture content tends to increase statistically. It shows (paired T-test, p <0.01) and retained skin moisture even after 11 days of application. Therefore, the composition containing Trans-3-O-galloyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone according to the present invention effectively preserves the moisture of the skin after application to maintain skin moisturizing ability. It turned out that it is excellent.

<Dose formulation example 1> Soft capsule 150 mg of post-fermented tea acetone fraction according to Example 2 of the present specification, lactose 440 mg, corn starch 430 mg and magnesium stearate 2 mg were mixed to produce a soft capsule filling liquid. Then, separately from the filling solution, a soft capsule sheet was produced at a ratio of 66 parts by mass of gelatin, 24 parts by mass of glycerin and 10 parts by mass of sorbitol solution, and the filling solution was filled to produce a soft capsule.

  Further, 3 mg of Trans-3-O-galoyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone, 440 mg of lactose, 450 mg of corn starch and 2 mg of magnesium stearate according to the examples of the present specification are mixed. Produce a soft capsule filling solution. Then, a soft capsule sheet was manufactured as described above, and the filling liquid was filled to manufacture a soft capsule.

<Formulation Example 2> Tablet A post-fermented tea acetone fraction 150 mg, vitamin E 15 mg, vitamin C 15 mg, galactooligosaccharide 250 mg, lactose 60 mg and maltose 140 mg according to Example 2 of the present specification are mixed, and fluidized bed dryer After granulation using the above, 8 mg of sugar ester was added. The composition was compressed into tablets by a conventional method.

  In addition, Trans-3-O-galoyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone 3 mg, vitamin E 15 mg, vitamin C 15 mg, galactooligosaccharide 259 mg, lactose 60 mg and maltose 140 mg were mixed according to the example. After granulation using a fluid bed dryer, 8 mg of sugar ester was added. The composition was compressed into tablets by a conventional method.

<Dose form example 3> Drink agent 80 mg of post-fermented tea acetone fractions according to Example 2 of the present specification, 9 mg of vitamin E, 9 mg of vitamin C, 10 g of glucose, 0.6 g of citric acid and 25 g of liquid oligosaccharide Then, 400 ml of purified water was added to this and filled in a bottle. After filling the bottle, it was sterilized at 30 ° C. for 4 to 5 seconds to produce a drink.

  In addition, Trans-3-O-galoyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone 0.1 mg, vitamin E 9 mg, vitamin C 9 mg, glucose 10 g, citric acid 0.6 g, and the examples. Twenty-five grams of liquid oligosaccharides were mixed, 400 ml of purified water was added thereto, and each bottle was filled with 200 ml. After filling the bottle, it was sterilized at 30 ° C. for 4 to 5 seconds to produce a drink.

<Dose form example 4> Granules 150 mg of post-fermented tea acetone fraction according to Example 2 of the present specification, 9 mg of vitamin E, 9 mg of vitamin C, 250 mg of anhydrous crystalline glucose and 550 mg of starch are mixed and fluidized bed granulator After granulating into granules, it was filled into packets to produce granules.

  Moreover, Trans-3-O-galoyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone 3 mg, vitamin E 9 mg, vitamin C 9 mg, anhydrous crystalline glucose 250 mg and starch 550 mg according to the example are mixed and flowed After granulation into granules using a layer granulator, the package was filled to produce granules.

<Formulation Example 5> Injection According to the composition shown in Table 2 below, an injection was manufactured by a usual method.

  Also, instead of the post-fermented tea acetone fraction, 3 mg of Trans-3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone of Example was used to prepare an injection.

<Dose Formulation Example 6> Health Food Health food was manufactured according to the conventional method according to the composition shown in Table 3 below.

  Also, instead of the post-fermented tea acetone fraction, a health food was manufactured using 3 mg of Trans-3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone of Example.

  Although the composition ratio of the vitamin and mineral mixture is a mixture composition taking as an example a component that is relatively suitable for health food, the composition ratio may be arbitrarily modified and implemented, as in the method for producing a general health food. After mixing the ingredients described above, they may be used for producing health food compositions in a conventional manner.

  <Formulation Example 7> Healthy Beverage

  As shown in Table 4 above, the remaining amount of purified water was added to a total volume of 900 ml, and the components were mixed according to a conventional method for producing a health drink, and then stirred and heated at 85 ° C for about 1 hour. After that, the prepared solution was filtered, put into a sterilized 2 liter container, sealed and sterilized, and then stored under refrigeration to produce a health drink.

  Also, instead of the post-fermented tea acetone fraction, 0.1 mg of Trans-3-O-galoyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone of Example is used to produce a health drink. did.

<Formulation Example 8> Soft Lotion (Skin Lotion)
3% by mass of post-fermented tea acetone fraction according to Example 2, 1.00% by mass of L-ascorbic acid-2-phosphate magnesium salt, 1.00% by mass of water-soluble collagen (1% aqueous solution), sodium citrate Soft lotion (skin lotion) using 0.10 mass%, citric acid 0.05 mass%, licorice extract 0.20 mass%, 1,3-butylene glycol 3.00 mass%, remaining amount as purified water Manufactured.

  Also, instead of the post-fermented tea acetone fraction, it is a soft makeup using 0.1 mass% of Trans-3-O-galloyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone of the example. I made water.

<Formulation Example 9> Cream-type preparation Post-fermented tea acetone fraction according to Example 2 3.00% by mass, polyethylene glycol monostearate 2.00% by mass, self-emulsifiable glyceryl monostearate 5.00% by mass , Propylene glycol 4.00% by mass, squalene 6.00% by mass, tri 2-ethylhexane glyceryl 6.00% by mass, glycosphingolipid 1.00% by mass, 1,3-butylene glycol 7.00% by mass, beeswax The cream type preparation was manufactured using 5.00 mass% and the remaining amount as purified water.

  Also, instead of the post-fermented tea acetone fraction, a cream type using 0.1% by mass of Trans-3-O-galloyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone of the example The formulation was manufactured.

<Dose formulation example 10> Pack The post-fermentation tea acetone fraction fraction 3.00 mass% according to Example 2, polyvinyl alcohol 13.00 mass%, L-ascorbic acid-2-phosphate magnesium salt 1.00 mass%, 1.00% by mass of lauroyl hydroxyproline, 2.00% by mass of water-soluble collagen (1% aqueous solution), 3.00% by mass of 1,3-butylene glycol, 5.00% by mass of ethanol, using the remaining amount as purified water The pack was manufactured.

  In addition, instead of the post-fermented tea acetone fraction, 0.1% by mass of Trans-3-O-galoyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone of Example is used to form a pack. Manufactured.

  While specific parts of the specification have been described above in detail, such specific descriptions are merely preferred embodiments for those of ordinary skill in the art, and this is the scope of the present description. It is obvious that is not limited. Accordingly, the substantial scope of the present specification can be said to be defined by the claims and their equivalents.

Claims (11)

3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone (3-O-galloyl-3,3 ', 5,5', 7-pentahydroxyflavan) represented by the following chemical formula 1, A moisturizing composition comprising the isomer, an acceptable salt thereof, a prodrug thereof, a hydrate thereof, a solvate thereof, or a post-fermented tea ketone fraction containing it as an active ingredient.

  The composition according to claim 1, wherein the post-fermented tea ketone fraction is a ketone fraction with respect to a water-insoluble extract of post-fermented tea.   The composition according to claim 1, wherein the ketone is acetone. The 3-O-galoyl-3,3 ′, 5,5 ′, 7-pentahydroxyflavone is a compound represented by Formula 2 below: Trans-3-O-galloyl-3,3 ′, 5,5 ′, 7 The composition according to claim 1, which is -pentahydroxyflavone (Trans-3-O-garyl-3,3 ', 5,5', 7-pentahydroxyflavan).

  3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone, its isomer, its acceptable salt, its prodrug, its hydrate, or its solvate in the above composition The composition according to claim 1, wherein the content of the substance is 0.000001% by mass to 5% by mass with respect to the total mass of the composition.   The composition according to claim 1, wherein the content of the post-fermented tea ketone fraction in the composition is 0.01% to 100% by mass based on the total mass of the composition.   The fraction is the 3-O-galloyl-3,3 ', 5,5', 7-pentahydroxyflavone, an isomer thereof, an acceptable salt thereof, a prodrug thereof, a hydrate thereof or The composition according to claim 1, wherein the solvate comprises 0.0001% to 5% by mass based on the total mass of the fraction.   Said 3-O-galoyl-3,3 ', 5,5', 7-pentahydroxyflavone (3-O-garyl-3,3 ', 5,5', 7-pentahydroxyflavan), its isomer, its tolerance The composition according to claim 1, wherein the dose of a possible salt, a prodrug thereof, a hydrate thereof or a solvate thereof is 0.0001 mg / kg / day to 15 mg / kg / day.   The composition according to any one of claims 1 to 8, wherein the composition is a food composition.   The composition according to any one of claims 1 to 8, wherein the composition is a pharmaceutical composition.   The composition according to any one of claims 1 to 8, wherein the composition is a cosmetic composition.

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