KR102139659B1 - Composition for improving the skin - Google Patents

Abstract

The present invention relates to a composition comprising picetin as an active ingredient, and the composition of the present invention has an effect of improving or preventing aging, wrinkles, elasticity, and moisture content of the skin, specifically collagen in the skin (type I ) And by promoting the synthesis of sulfated glycosaminoglycan, it has the effect of fundamentally improving and preventing wrinkles, aging, and elasticity of the skin. It is derived from natural substances and has low toxicity and low side effects. Or it can be very useful as an active ingredient such as food.

Description

Composition for improving the skin}

The present invention relates to a cosmetic, health functional food and pharmaceutical composition for improving skin.

The skin is an important organ responsible for various physiological functions such as the function of protecting the human body from the external environment, the barrier function that prevents the internal moisture and useful components from flowing out, the body temperature control function, and the excretion function. As the aging of an individual progresses, the skin also undergoes aging that loses these important functions. In general, the main causes of skin aging can be largely divided into endogenous factors, such as an increase in natural age and exogenous factors such as sunlight damage. have. As a result of skin aging caused by internal and external factors, wrinkles and elasticity decrease, which are mainly caused by damage and changes in the dermal layer.

The structure of the skin is largely classified into epidermal, dermal, and subcutaneous layers. The dermal layer is the actual skin, which accounts for 90% of the skin, and is composed of collagen fibers and elastic fibers, connective tissue, and a substrate filling the cells and connective tissue. Collagen fibers are produced in fibroblasts, and important functions are known as mechanical firmness of the skin, resistance of connective tissue and adhesion of tissue, and support of cell adhesion. The amount of collagen decreases with age and the structure is damaged, and this has been pointed out as a major cause of endogenous skin aging and wrinkles. In addition, collagen fiber damage caused by ultraviolet rays can be seen as a cause of exogenous skin aging and wrinkles. Elastic fiber is an important material that maintains the elasticity of the skin. When degeneration occurs due to various causes, it leads to a decrease in skin elasticity. The matrix is a substance that fills the cells between the connective fibers of the dermis and the cells. Glycosaminoglycan, a hydrophilic polysaccharide that forms a substrate, is also called mucopolysaccharide because it is dissolved in water and exists in mucus.

Glycosaminoglycan (GAG) is a structure in which sugars in the form of disaccharides are repeatedly connected, hyaluronic acid, chondroitin sulfate, heparan sulfate, heparin, and keratin sulfate (keratan) sulfate) and dermatan sulfate. GAG can be roughly divided into two types: hyaluronic acid, a GAG that does not contain a sulfate group, and the remaining five types, which contain a sulfate group.

GAG is mainly present in the extracellular matrix (ECM) in the skin and serves to fill the empty space between collagen fibers and elastic fibers, which occupy a large part of the ECM, and recognizes changes in surrounding proteins or changes in cells. Signal. This affects the growth or differentiation and normal function of cells. In addition, GAG plays an important role in maintaining moisture in the skin due to its excellent binding ability with water molecules. As the skin aging progresses due to internal and external causes, the amount of GAG present in the dermis decreases and the ability to newly synthesize GAG decreases. This increases the empty space of the dermal layer, thereby reducing wrinkles, reducing skin elasticity, and reducing moisture. Results.

The anti-wrinkle and anti-wrinkle cosmetic used to improve skin aging and wrinkles can be said to be representative of products containing vitamin A (retinol) or retinyl palmitate. However, products containing these raw materials are not only susceptible to changes over time, but when they penetrate or decompose the skin beyond the effective concentration, the amount of use has been limited due to significant skin irritation and stability problems such as redness, and practical wrinkle prevention and improvement effects And the moisturizing effect was minimal.

While it is possible to fundamentally improve the skin aging and wrinkles, moisturizing ability, and the like, the development of non-toxic anti-aging agents has been continuously required. In order to solve this problem, the present inventors prevent aging of the skin, Continuing research on skin-improving parts that can suppress the occurrence of wrinkles, confirms that pisetin has an excellent effect of promoting the synthesis of sulfated glycosaminoglycan and collagen type I of skin cells, and the present invention Was completed.

Accordingly, an object of the present invention is to provide a cosmetic composition, a pharmaceutical composition and a food composition having a skin improvement effect.

In order to achieve the above technical problem, the present invention provides a cosmetic composition comprising ficetin (fisetin) or a derivative thereof as an active ingredient.

The composition may be for promoting the synthesis of sulfated glycosaminoglycan.

The composition may be for promoting collagen synthesis.

The composition may be for improving or preventing skin aging, skin wrinkles, skin elasticity reduction, skin moisture content reduction or aging.

The content of phycetin contained in the composition may be 1×10 ^-5 to 10% by weight of the total composition.

The cosmetic composition is a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, foundation, cosmetic water, cosmetic ointment, spray, pack, sunscreen, makeup base, powder , May have a formulation selected from the group consisting of makeup removers and detergents.

In addition, the present invention provides a cosmetic product comprising fisetin or a derivative thereof as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for the prevention and treatment of skin damage diseases comprising ficetin or a derivative thereof as an active ingredient.

The skin damage disease may be selected from the group consisting of skin redness (erythema), skin aging, skin wrinkles, skin capillaries, skin elasticity reduction and skin moisture content reduction.

The pharmaceutical composition is a skin having a formulation selected from the group consisting of ointments, creams, tablets, pills, powders, granules, capsules, suspensions, intravenous solutions, emulsions, syrups, aqueous solutions, non-aqueous solvents, suspensions and emulsions It can be for the prevention and treatment of damaged diseases.

In addition, the present invention provides a health functional food composition for improving or preventing skin aging, skin wrinkles, skin elasticity reduction or skin moisture content reduction, which includes fisetin or a derivative thereof as an active ingredient.

The present invention is a composition containing picetin as an active ingredient has the effect of improving or preventing aging, wrinkles, elasticity, and moisture content of the skin, specifically collagen (Type I) and sulfated glycosaminoglycol in the skin By promoting the synthesis of cells, it improves the mechanical robustness of the skin and has the effect of fundamentally improving and preventing wrinkles, aging, and elasticity of the skin. It is derived from natural substances and has less toxicity and side effects. It can also be very useful for food compositions.

The present invention relates to a cosmetic composition comprising fisetin or a derivative thereof as an active ingredient.

The ficetin may be represented by Formula 1 below.

[Formula 1]

The compound name of the compound of Formula 1 is 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one (2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen -4-one), and is commonly called fisetin.

The ficetin corresponds to one of the types of flovonoids, and refers to a compound having C ₁₅ H ₁₀ O ₆ and molecular weight=286. The ficetin generally has yellow needle-like crystals, a melting point of 360° C. or higher, and recrystallization from dilute acetic acid may contain six molecules of crystal water. It can be extracted and purified from natural extracts.

The phycetin can be chemically synthesized through various organic chemical methods known in the art, and can also be easily obtained from plants and the like. Picetin used in the present invention was purchased and used from Sigma aldrich (USA).

The derivatives of picetin mean all of the compounds in which some structures of picetin are substituted or changed, and exhibit similar effects to those of the present invention.

The phycetin is an effective ingredient for inhibiting, treating and improving wrinkles caused by wrinkles related to collagen reduction and elasticity reduction or synthetic degradation and degradation degradation of sulfated glycosaminoglycan, another component of the extracellular dermal matrix. It can be used as and can also be used as an active ingredient for wound healing due to its excellent healing efficacy in skin wounds. In addition, since a good effect is maintained even when contained in a small amount, it can be used in various formulations as an active ingredient for improving or preventing skin wrinkles, skin elasticity, or skin aging in pharmaceuticals or cosmetics, and has a wide range of applications. have.

It was confirmed that the pisetin promotes biosynthesis of sulfated glycosaminoglycans and collagen type I, thereby exhibiting an effect of maintaining collagen type I and dermal extracellular matrix composition of the skin tightly.

In a specific embodiment, in order to investigate the effect of ficetin on fibroblasts and keratinocytes derived from the human body, the production of sulfated glycosaminoglycan and collagen type I when ficetin is treated on the human fibroblasts It was confirmed that this increase (Table 1 and Table 2). The ficetin can promote the expression of HAS-2, HAS-3, and in an embodiment of the present invention, to investigate the effect of enhancing the expression of HAS-2, HAS-3 of picetin to keratinocytes derived from the human body It was confirmed that the expression of HAS-2 and HAS-3 increased when treated with picetin (Table 3).

Accordingly, the cosmetic composition of the present invention may be a cosmetic composition for promoting the synthesis of sulfated glycosaminoglycan and/or for promoting collagen synthesis.

In addition, the cosmetic composition of the present invention may be a cosmetic composition for moisturizing the skin.

The cosmetic composition containing the phycetin can improve the skin by increasing the production of sulfated glycosaminoglycans in the skin, and also promoting the production of type I collagen and promoting the expression of HAS, thereby improving skin. It may be for improving or preventing skin aging, skin wrinkles, skin elasticity reduction, or skin moisture content reduction.

In the case of using the composition of the present invention, it was experimentally confirmed that an increase in skin moisture content and an increase in water retention capacity (Table 4), and an improvement in skin elasticity, prevention of aging prevention, or improvement of skin wrinkles were also experimentally confirmed (Table) 5).

The term'skin aging' refers to symptoms such as decreased elasticity, reduced gloss, wrinkle formation, weakening of regenerative power, or severe dryness on the skin, which may be caused by the passage of time or the external environment, and sulfated together with collagen and elastin. When extracellular matrix components such as glycosaminoglycan are reduced, skin elasticity may be reduced or skin wrinkles may be generated, which may be caused by their reduction.

The term'skin wrinkles' of the present invention refers to fine lines formed on the skin, which may be caused by genes, reduction of collagen present in the dermis of the skin, external environment, etc., and structural support of cells such as elastin and collagen When the sulfated glycosaminoglycan is reduced, skin wrinkles are formed.

The term'skin elasticity' is indicated by elastic fibers composed of elastin present in the dermal layer. These elastic fibers have very low elastic modulus, such as rubber, so they are easily deformed by small forces, and their strength When removed, it easily returns to its original shape. The reduction of the sulfated glycosaminoglycan not only reduces collagen and elastin, but also makes it difficult to maintain the structure, resulting in a decrease in skin elasticity.

The term'moisturizing' refers to maintaining the homeostasis of the living body by appropriately controlling water loss (water evaporation), and water loss may occur when hyaluronic acid in the skin and sulfated glycosaminoglycan are reduced.

The term'prevention' refers to inhibiting or delaying the aging of the skin or the generation of wrinkles, the decrease in elasticity or moisture content, or the fibroblasts, regardless of the cause of aging using the composition of the present invention. It means to inhibit or delay through the action to promote the biosynthesis of sulfated glycosaminoglycan and collagen type I in keratinocytes.

The term'improvement' refers to all acts of improving or beneficially changing the skin condition by maintaining or strengthening the ability related to wrinkles, aging and elasticity of the skin, specifically promoting the synthesis of sulfated glycosaminoglycans It means not only the reduction of elastin and collagen, but also maintaining their structure, improving skin wrinkles, aging, elasticity or moisture content.

The content of picetin contained in the composition may be included in an effective amount.

The term'effective amount' refers to an amount of picetin that can suppress or delay the aging or wrinkle formation of the skin or alleviate wrinkles that have already been generated.

The effective amount of the phycetin contained in the composition for improving wrinkles of the present invention will vary depending on the form in which the composition for improving wrinkles is commercialized, the method in which the phycetin is applied to the skin, and the time to stay on the skin. For example, when the composition for improving wrinkles is commercialized as a pharmaceutical product for dermatological treatment according to the formation of wrinkles on the skin, it may contain picetin at a higher concentration than when commercialized as a cosmetic that is applied to skin on a daily basis. . Even in the case of being commercialized as a cosmetic product, in the case of a wash-off type cosmetic product such as a makeup remover, a detergent, etc., in which the active ingredient stays on the skin within a short period of time, a relatively high concentration of ficetin may be included. On the other hand, in the case of a leave-on type cosmetic such as lotion, emulsion, cream, essence, etc., in which the active ingredient stays on the skin for a long period of time, it may be acceptable to include a lower concentration of ficetin than a wash-off type cosmetic. will be.

The content of picetin contained in the composition may be specifically 1×10 ^-5 to 10% by weight of the total composition. It is difficult to obtain the effect of the above component at a concentration of less than 0.00001% by weight, and at a concentration of more than 10% by weight, the overall processability of the composition, such as solubility as a solvent, is poor, and there is a concern that use in various applications such as cosmetic formulations described later may be limited. have.

In addition, the preferred concentration of picetin included in the composition is 0.1 μg/ml to 100 μg/ml, more preferably 1 μg/ml to 50 μg/ml, even more preferably 5 μg/ml to 25 μg/ml Can be

The cosmetic composition can be used in any formulation that can be applied to the skin. Specific examples include solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, foundations, cosmetic water, cosmetic ointments, sprays, packs, sunscreens, makeup bases, powders, makeup It may have a formulation selected from the group consisting of removers and detergents, but is not limited to the above examples.

In addition, the cosmetic composition may be used as a skin external agent for promoting skin elasticity, preventing skin aging, and improving skin wrinkles.

In one embodiment of the present invention, it has been confirmed that when phycetin is prepared as an external ointment or an essence formulation, and when it is applied to human skin, it exhibits an excellent skin wrinkle improvement effect. Particularly, it was confirmed that in the present invention, picetin exhibits an excellent wrinkle improvement effect even when applied at a low concentration level, that is, in a small amount.

The cosmetic composition containing picetin according to the present invention is a cosmetically acceptable carrier, diluent, adjuvant, colorant, stabilizer, flavoring agent, surfactant, oil, moisturizer, alcohol, thickener, oxidation for easy use and handling It may contain additional inhibitors, pH adjusting agents, sunscreens, etc., and when used as a composition for external application of the skin, it is a liquid, oily, creamy, ointment, sticky, pack, pasta, powder, etc. Also available.

The cosmetic composition may further include a cosmetically acceptable excipient for ease of use and handling. The cosmetically acceptable excipients include surfactants, emulsifiers, soap acids, solvents, binders, diluents, lubricants, stabilizers, fragrances, water, lower alcohols, thickeners, chelating agents, pigments, preservatives, colorants, preservatives, antibiotics, Antioxidants, anti-foaming agents, antibacterial agents, anti-redeposition agents, enzymes, plant or mineral oils, fats, fluorescent substances, fungicides, oleogenic agents, moisturizers, fragrances, fragrance carriers, preservatives, proteins, silicones, solubilizers, sugar derivatives, sunlight Blockers, vitamins, plant extracts or waxes can be exemplified, and these may be included alone or in combination of two or more.

When the cosmetic composition is formulated as a cosmetic, it may include a skin-acceptable known excipient that acts as a carrier for the active ingredient, specifically, International cosmetic ingredient dictionary, 6th ed., The cosmetic, Toiletry and Fragrance Association , Inc., Washington, 1995. The above documents are included as part of the present specification.

In addition, the present invention relates to a cosmetic product comprising fisetin or a derivative thereof as an active ingredient.

The cosmetic product may be one having a formulation selected from the group consisting of cosmetic products, essences, skins, lotions, creams, and packs.

The cosmetics are, for example, skin, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, pionation, essence, nutrition essence, pack, arsenic, Cleansing foam, cleansing lotion, cleansing cream, body lotion and body cleanser, but are not limited thereto.

In addition, the present invention relates to a pharmaceutical composition for the prevention or treatment of skin damage diseases comprising ficetin (fisetin) or a derivative thereof as an active ingredient.

In addition, the present invention relates to a drug or quasi-drug containing the pharmaceutical composition.

The pharmaceutical composition means a medicine used for the purpose of diagnosing, treating, alleviating, treating or preventing diseases of animals including humans.

The skin damage disease refers to a disease caused by skin damage, specifically selected from the group consisting of skin redness (erythema), skin aging, skin wrinkles, skin capillaries, skin elasticity reduction, skin moisture content reduction and aging. Can be one

The preferred dosage of the pharmaceutical composition of the present invention depends on the subject's age, sex, weight, symptoms, degree of disease, drug form, route of administration and duration, but may be appropriately selected by those skilled in the art. For the desired effect, it is preferable to administer the pharmaceutical composition of the present invention at 0.01 to 1000 mg/day. Administration can be done once a day or divided several times. In addition, the dosage may be increased or decreased depending on age, gender, weight, disease severity, and route of administration. Therefore, the dosage does not limit the scope of the present invention in any way.

The composition may be administered to mammals such as rats, mice, livestock, and humans by various routes such as parenteral or oral administration, and all modes of administration can be expected. For example, oral, rectal or intravenous, muscle , Can be administered by subcutaneous, intrauterine dura or intracerebroventricular injection.

The pharmaceutical composition for the prevention or treatment of skin damage diseases of the present invention may contain the above-mentioned picetin alone as an active ingredient, and other pharmaceutically acceptable carriers, excipients, diluents and/or other formulations, methods of use and purpose of use. Or it may further include a sub-component.

More specifically, in addition to the above-mentioned active ingredients, nutrients, vitamins, electrolytes, flavoring agents, coloring agents, neutralizing agents, pectic acids and salts thereof, alginic acids and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, Glycerin, alcohol, carbonic acid used in carbonated beverages and the like may be further included.

The term'pharmaceutically acceptable' means that when administered to a physiologically acceptable animal, preferably a human, it usually does not cause an allergic reaction such as gastrointestinal disorders, dizziness or similar reactions. The pharmaceutically effective amount may be appropriately changed according to the disease and its severity, the patient's age, weight, health status, sex, administration route, and treatment period.

Examples of the pharmaceutically acceptable carrier, excipient, or diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, propylhydroxybenzoate, talc, magnesium stearate and mineral oil , Dextrin, calcium carbonate, dextrin, calcium carbonate, propylene glycol, liquid paraffin, and one or more selected from the group consisting of physiological saline, but is not limited thereto, and a common carrier, excipient, or diluent may be used.

The ingredients may be added to the active ingredient, picetin, independently or in combination.

The formulation of the pharmaceutical composition may vary depending on the method of use, and is formulated using a method well known in the art to which the present invention pertains to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. Can be. Examples of the formulation may be a formulation selected from the group consisting of ointments, creams, tablets, pills, powders, granules, capsules, suspensions, intravenous solutions, emulsions, syrups, aqueous solutions, non-aqueous solvents, suspensions and emulsions. .

For the formulation, excipients, for example, conventional fillers, extenders, binders, disintegrants, surfactants, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives, sweeteners, fragrances or preservatives may be further included.

In general, solid preparations for oral administration include tablets, pills, soft or hard capsules (CAPSULES), pills (PILLS), powders (POWDERS) and granules (GRANULES), etc. Excipients, for example, may be prepared by mixing starch, calcium carbonate, sucrose or lactose, gelatin, and the like. In addition, lubricants such as magnesium stearate and talc may be used in addition to simple excipients.

In addition, liquid preparations for oral administration include suspensions (SUSTESIONS), intravenous solutions, emulsions (EMULSIONS), and syrups (SYRUPS), and various excipients, such as water or liquid paraffin, which are commonly used simple diluents, include, Wetting agents, sweeteners, fragrances, preservatives, and the like may be included.

Examples that may be mentioned for skin administration are suitable for producing dusting powders, emulsions, suspensions, oils, sprays, ointments, draw ointments, cream pastes, gels, foams, or solutions, and transdermal therapeutic systems (TTS). ) Suitable carriers and/or excipients. The topical pharmaceutical preparations of the present invention may be semi-solid dosage forms, in particular ointments (solution ointments, suspension ointments), creams, gels or pastes. Mainly used in the oil phase are fatty alcohols such as lauryl alcohol, cetyl alcohol, stearyl alcohol, fatty acids such as palmitic acid or stearic acid, liquid or solid paraffin or ozokerite, liquid to solid wax, eg For example isopropyl myristate, natural fat or some synthetic fat, for example coconut fatty acid triglyceride, hydrogenated oil, for example hydrogenated peanut or castor oil, or fatty acid partial ester of glycerol, for example glycerol monostearate or glycerol Distearate. Suitable emulsifiers include surfactants, such as nonionic surfactants, such as polyalcohols or fatty acid esters of ethylene oxide adducts thereof, such as polyglycerol fatty acid esters or polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters, such as Sorbitan oleate and/or sorbitan isostearate, etc., isostearate, sterol, or polyoxyethylene fatty alcohol ether or fatty acid esters such as anionic surfactants, such as alkali metal salts of fatty alcohol sulfonates, Examples are sodium lauryl sulfate, sodium cetyl sulfate or sodium stearyl sulfate, which are commonly used in the presence of the above fatty alcohols, for example cetyl alcohol or stearyl alcohol. Among them, it is possible to add a cream-preventing agent, for example, polyalcohol, such as glycerol, sorbitol, propylene glycol and/or polyethylene glycol, to the aqueous phase or preservatives, fragrances, and the like to the aqueous phase.

The pharmaceutical preparation of the present invention may be an ointment in an anhydrous state, and is suitable for topical use and contains liquid paraffin, especially low-viscosity paraffin, at body temperature, or the natural fat or partially synthetic fat, such as coconut fatty acid triglyceride. Cerides, hydrogenated oils such as hydrogenated peanut or castor oils, fatty acid partial esters of glycerol, such as glycerol monostearate and distearate, silicones such as polymethylsiloxanes such as hexamethyldisiloxane or octamethyltri It may contain siloxanes, for example, fatty alcohols associated with aqueous creams and which increase the water absorption capacity, and may contain sterols, wool wax, other emulsifiers and/or other additives.

In the present invention, when the pharmaceutical composition is formulated as a pharmaceutical, reference may be made to the contents disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA, and the documents are included as part of the present specification.

In addition, the pharmaceutical composition of the present invention may be used alone or in combination with methods using surgery, hormonal therapy, drug therapy, and biological response modifiers for improvement, alleviation, treatment or prevention of skin.

Above, the numerical values described in this specification should be interpreted to include even ranges unless otherwise specified.

In addition, the present invention relates to a health functional food composition for improving or preventing skin aging, skin wrinkles, skin elasticity reduction or skin moisture content, which includes fisetin or a derivative thereof as an active ingredient.

The food means a natural product or a processed product containing one or more nutrients, and preferably means a state that can be directly eaten after a certain process, and is a health functional food in a general sense. It is intended to include functional foods, beverages, food additives, and beverage additives.

The food may be, for example, various foods, beverages, chewing gum, tea, vitamin complexes, health functional foods, and the like. In addition, in the present invention, foods include special nutritional foods (e.g., delicatessen, young, baby food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (e.g. ramen, noodles, etc.), health supplements, seasoned foods ( Yes, soy sauce, miso, red pepper paste, mixed sauce, etc., sauces, confectionery (e.g., snacks), dairy products (e.g. fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi, pickles, etc.), beverages ( Examples include, but are not limited to, fruit and vegetable beverages, soy milk, fermented beverages, etc.), and natural seasonings (eg, ramen soup, etc.).

The food, functional food, health functional food, beverage, food additives and beverage additives can be prepared by a conventional manufacturing method.

In the present invention, the health functional food is a food group or food composition that provides added value to act and express the function of the food by using physical, biochemical, and biotechnological techniques, etc. Refers to a food product that has been designed and designed to sufficiently express the body control functions related to recovery.

The dietary supplement may include a food-acceptable food supplement additive, and may further include suitable carriers, excipients, and diluents commonly used in the manufacture of dietary supplements.

In the present invention, a drink means a generic term for drinking to relieve thirst or to enjoy a taste, and is intended to include a health functional beverage.

The beverage is an essential component in the indicated proportions, and there is no particular limitation on other components other than including the extract as an active ingredient, and may contain various flavoring agents or natural carbohydrates, etc., as additional components, as in conventional beverages.

Examples of the natural carbohydrate may be monosaccharides such as glucose or fructose, disaccharides such as maltose, sucrose, polysaccharides such as dextrin, cyclodextrin, or sugar alcohols such as xylitol, sorbitol, and erythritol. . The flavoring agent may be a natural flavoring agent such as taumatin or rebaudioside A or a stevia extract such as glycyrrhizine, or a synthetic flavoring agent such as saccharin or aspartame.

The amount of the natural carbohydrate added may be about 1 g to 20 g, preferably 5 g to 12 g per 100 ml of the food composition of the present invention. In addition, the composition of the present invention may further contain flesh for the preparation of natural fruit juice, fruit juice drink, vegetable drink.

In addition to the above, the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and neutralizing agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and It may contain salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonic acid used in carbonated beverages, and the like.

These components can be used independently or in combination. The proportion of these additives is not critical, but may be selected from 0 to 2,000 parts by weight per 100 parts by weight of the extract of the present invention.

The health functional beverage is a beverage group or a beverage composition having added value to act and express the function of the corresponding beverage by using physical, biochemical, or biotechnological methods on the beverage, control of biological rhythm of the beverage composition, prevention and recovery of diseases It means a beverage that has been designed and processed so as to sufficiently express the body control function related to the body.

The health functional beverage is an essential component in the indicated proportions, and there is no particular limitation on other components other than the one containing the ficetin of the present invention, and may contain various flavoring agents or natural carbohydrates, etc., as additional components, such as ordinary beverages.

Examples of the natural carbohydrate may be monosaccharides such as glucose or fructose, disaccharides such as maltose, sucrose, polysaccharides such as dextrin, cyclodextrin, or sugar alcohols such as xylitol, sorbitol, and erythritol. . The flavoring agent may be a natural flavoring agent such as taumatin or rebaudioside A or a stevia extract such as glycyrrhizine, or a synthetic flavoring agent such as saccharin or aspartame.

The amount of the natural carbohydrate added may be about 1 g to 20 g, preferably 5 g to 12 g per 100 ml of the food composition of the present invention. In addition, the composition of the present invention may further contain flesh for the preparation of natural fruit juice, fruit juice drink, vegetable drink.

In addition to the above, the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and neutralizing agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and It may contain salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonic acid used in carbonated beverages, and the like. These components can be used independently or in combination. The proportion of these additives is not so critical, but may be selected from 0 to 20 parts by weight per 100 parts by weight of the present phycetin.

The health functional food may additionally include food additives, and whether or not it is suitable as a food additive is a standard and a standard related to the item according to the General Regulations and General Test Methods of the Food Additives Code approved by the Food and Drug Administration unless otherwise specified. It is judged by.

The extract of the present invention, which is added to foods including beverages in the process of manufacturing a health functional food of the present invention, can appropriately adjust its content as necessary, preferably 0.00001 to 10% by weight relative to 100% by weight of the total food It can be added to include.

In addition, the present invention relates to a method for improving skin comprising the use of or taking an effective amount of picetin to the skin for use in the preparation of the cosmetic, pharmaceutical or food composition.

Hereinafter, preferred embodiments are provided to help understanding of the present invention. However, the following examples are only provided to more easily understand the present invention, and the contents of the present invention are not limited by the examples.

[ Example 1] Confirmation of the effect of promoting the synthesis of collagen type I in human-derived fibroblasts

Pycetin was added to the culture medium of human-derived fibroblasts to confirm the effect of promoting collagen synthesis at the cellular level. The used pisetin was purchased from Sigma Aldrich (USA) and used. The measured collagen was quantified using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immuno Assay KIT).

In the experiment, the final concentrations of picetin were 10 μg/ml and 20 μg/ml. Pycetin was added to the culture medium of human-derived fibroblasts (DMEM medium), cultured for 48 hours, and then the culture solution was taken, and the degree of collagen synthesis at each concentration was measured at 450 nm using a PICP EIA kit using a spectrophotometer.

In order to compare the effect, the degree of collagen synthesis was measured in the same manner for the sample in which the culture medium of the fibroblasts without addition (control) and TGF-beta were added to a final concentration of 10 ng/ml.

The increase rate of collagen production was calculated as the ratio of the amount of collagen production relative to the control group, and the results are shown in Table 1 below.

sample Collagen production (ng/ml)) Growth rate (%) Control 178 - TGF-beta 10 ng/ml 470 164 Picetin 10 μg/ml 297 67 Picetin 20 µg/ml 335 88 (Number of repetitions=4)

[ Example 2] in human fibroblasts Sulfated Glycosaminoglycan Confirm the effect of promoting synthesis

Pycetin was added to the culture medium of human-derived fibroblasts (Human fibroblast) to confirm the effect of promoting the synthesis of sulfated glycosaminoglycans at the cellular level. The measurement of sulfated glycosaminoglycan was quantified using a Blyscan glycosaminoglycan assay kit (Biocolor).

In the experiment, final concentrations of picetin were 1 μg/ml, 10 μg/ml, and 20 μg/ml. Picetin is added to the culture medium (DMEM medium) of human-derived fibroblasts (Human fibroblast), incubated for 24 hours, and then the culture is taken. Measurement was made at 656 nm using a photometer.

The increase rate of production of sulfated glycosaminoglycan was calculated as a ratio of the amount of sulfated glycosaminoglycan produced relative to the culture medium (control) of fibroblasts to which nothing was added, and the results are shown in Table 2 below.

Sample (µg/ml) Production amount of sulfated glycosaminoglycan (ng/ml) Growth rate (%) Control 0.46 - Picetin 1 μg/ml 0.54 17 Picetin 10 μg/ml 1.56 239.1 Picetin 20 µg/ml 4.00 769.5 (Number of repetitions=4)

As shown in Table 2, it was confirmed that there is an excellent effect of synthesizing sulfated glycosaminoglycans at 10 µg/ml and 20 µg/ml, respectively, compared to the control group not treated with ficetin.

[ Example 3] Increased expression of hyaluronic acid synthase (HAS) gene by picetin in human keratinocytes

Human-derived keratinocytes were cultured at 1x10 ⁶ cells/ml in DMEM medium containing 10% fetal bovin serum, and then cultured for 18 hours by dispensing 3000 μl into 6-well plates for 18 hours. Washed twice with undiluted DMEM medium. Picetin was treated at 1 ppm for 24 hours. To recover the cells, the extraction of the total RNA after, quantified by RNeasy mini kit (Qiagen) was used for the RNA of ^{1㎍ GeneAmp ® RNA PCR kit (Applied} Biosystems) RT (reverse transcription). The reverse transcription reaction was performed using a Mycycler ^® PCR instrument (Biorad).

Subsequently, quantitative real time PCR was performed using 2 μl of a reverse transcription reaction solution and Taqman ^® probe (Invitrogen, USA, HS02511055_S1, HS03929097_g1) of HAS-2, HAS-3, and GAPDH (Glyceraldehyde-3-phosphate dehydrogenase). Real time PCR was performed using a CFX96 Touch ^TM Real-Time PCR Detection System instrument (Biorad). Experimental results obtained through real-time PCR were calculated by using the method described in Livak KJ et al. (Methods, 2001, 25, 402-408) based on GAPDH, a housekeeping gene.

In addition, based on the mRNA expression level of the negative control as a reference (100%), the mRNA expression level of the test group treated with pisetin was quantified and shown in Table 3.

sample No treatment
(Negative control) Glucosamine
100 ppm Picetin
1 ppm Picetin
10 ppm HAS-2
Expression level (%) 100 114 111 131 HAS-3
Expression level (%) 100 125 119 140

* Number of repetitions = 4

As shown in Table 3, the expression of hyaluronic acid synthase, particularly HAS-2 and HAS-3, was increased in human keratinocytes derived from human body by treatment with picetin. In addition, it was confirmed that picetin showed expression levels of HAS-2 and HAS-3 similar to those of the positive control in an amount 100 times smaller than that of the positive control, and showed higher expression than the control in an amount of 10 times less. Through this, it was confirmed that even with a small amount of picetin, it had a moisturizing effect on excellent skin moisture retention reduction.

[ Manufacturing example 1 and Comparative example 1] Preparation of external skin ointment

As shown in the composition of Table 4, an external ointment for skin containing picetin as an active ingredient was prepared according to a conventional method. In addition, an external ointment for skin prepared with the rest of the components except the active ingredient was prepared as Comparative Example 1.

Composition (% by weight) Preparation Example 1 (% by weight) Comparative Example 1 (% by weight) Picetin 0.2 0 Diethyl sebacate 8 8 Arrears 5 5 Polyoxyethylene oleyl ether phosphate 6 6 Sodium benzoate One One vaseline to 100 to 100

[ Manufacturing example 2 and Comparative example 2] Preparation of Essence

The skin aging prevention and wrinkle improvement cosmetic essence containing picetin as an active ingredient was prepared in Preparation Example 2, and the cosmetic essence prepared in the same manner as in Production Example 2 was used as Comparative Example 2, except that the active ingredient was not included. Did. The detailed composition is shown in Table 5 below.

Composition (% by weight) Preparation Example 2 (% by weight) Comparative Example 2 (% by weight) Picetin 0.5 0 glycerin 10.0 10.0 Sodium hyaluronate aqueous solution (1%) 5.0 5.0 Polyoxyethylene cured castor oil 1.0 1.0 Methyl paraoxybenzoate 0.1 0.1 Spices 0.05 0.05 Purified water to 100 to 100

[ Experimental Example 1] Confirmation of skin wrinkle improvement effect through panel test

For the essences of Preparation Example 2 and Comparative Example 2, the effect of improving skin wrinkles was tested on healthy women aged 35 to 50 as follows.

30 women from 35 to 50 years old are divided into two groups of 15 each, group 1 contains the essence of preparation example 2 containing 0.5% of phycetin, group 2 receives the essence of comparative example 2 on the face 1 day It was applied for 3 months. After 3 months, the degree of improvement in skin wrinkles was evaluated through a subject's questionnaire. The subject's questionnaire was judged as three steps of no improvement, slight improvement, and significant improvement as compared to before use with respect to skin wrinkle improvement and elasticity enhancement, and the results are shown in Table 6 below.

Division (person) No improvement Slight improvement Significant improvement Preparation Example 2 One 7 7 Comparative Example 2 9 4 2

As shown in Table 6, when using the essence of Preparation Example 2 containing 0.5% of ficetin, it was confirmed that the skin wrinkle improvement effect is better than the case of using the essence of Comparative Example 2 without use.

[ Experimental Example 2] Through image analysis Cosmetic Essence wrinkle improvement effect test

The wrinkle improvement effect of the essence of Preparation Example 2 and Comparative Example 2 was evaluated through image analysis.

Specifically, before the experiment was started, a replica under the eyes was collected (Xantopren, Bayer), and immediately after the experiment was completed, the replica was collected at the same area under the eyes, and two-dimensional skin wrinkles were analyzed through image analysis. The density of skin wrinkles was determined by analysis. The reduction rate of skin wrinkle density by image analysis is an average value of the ratio of skin wrinkle density after use to skin wrinkle density before use of essence, and the measurement results are shown in Table 7 below.

Skin wrinkle density reduction rate (%) Comparative Example 2 14 Preparation Example 2 56

As shown in Table 7, it can be seen that when using the essence of Preparation Example 2 containing picetin, the effect of improving skin wrinkles is superior to the case of using the essence of Comparative Example 2 that does not contain picetin. In addition, no skin irritation or side effects caused by the essence of Preparation Example 2 were found in the test procedure.

Claims (11)

A cosmetic composition for moisturizing skin comprising ficetin as an active ingredient. According to claim 1,
The composition is a cosmetic composition for moisturizing the skin, which promotes the synthesis of sulfated glycosaminoglycan. According to claim 1,
The content of phycetin contained in the composition is 1×10 ^-5 to 10% by weight of the total composition. According to claim 1,
The cosmetic composition is a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, foundation, cosmetic water, cosmetic ointment, spray, pack, sunscreen, makeup base, powder , Cosmetic composition for moisturizing the skin having a formulation selected from the group consisting of a makeup remover and a cleaning agent. Cosmetics for moisturizing skin comprising the composition according to claim 1. A pharmaceutical composition for preventing or treating skin moisture-containing deterioration comprising ficetin as an active ingredient. The method of claim 6,
The pharmaceutical composition is a skin having a formulation selected from the group consisting of ointments, creams, tablets, pills, powders, granules, capsules, suspensions, intravenous solutions, emulsions, syrups, aqueous solutions, non-aqueous solvents, suspensions and emulsions Pharmaceutical composition for the prevention or treatment of water content reduction. A health functional food composition for improving or preventing skin moisturization or deterioration in moisture content of skin containing ficetin as an active ingredient. delete delete delete