KR20170046028A - Composition for whitening containing extract of unripe fruit - Google Patents

Abstract

The present invention relates to a cosmetic composition, a food composition, a pharmaceutical composition for inhibiting pigment deposition, and cosmetics, food, and medicinal materials containing the same, as an active ingredient, It has an effect of inhibiting the enzymatic activity of tyrosinase without exhibiting cytotoxicity and effectively inhibiting the expression of melanin biosynthesis and genes associated therewith and thus being useful for preventing or treating skin whitening and pigmentation , It is extracted from plants that have been used for a long time and unlike artificially synthesized compounds, there is no problem of side effects and safety is recognized. Therefore, not only pharmaceutical compositions such as cosmetic compositions and medicines for developing cosmetics, but also food compositions including health functional foods Can be useful The.

Description

Technical Field [0001] The present invention relates to a composition for preventing whitening,

The present invention relates to a composition for whitening comprising an immature extract and an extract.

Recently, there has been an increase in skin changes caused by an increase in average life span, an increase in leisure activities, and environmental pollution caused by rapid industrialization, resulting in destruction of the ozone layer and increase in ultraviolet exposure. In this environment, the skin pigmentation caused by ultraviolet rays and the photoaging caused by photoaging are getting worse, and the interest in skin coloring is increasing day by day. Recently, functional cosmetics industry has been actively researched in the field of skin aging prevention and skin whitening. In the domestic cosmetics market, sales of functional cosmetics are on the rise as of 2012, The market size is also steadily increasing.

Human skin color depends on internal and external factors. Among them, the most fundamental internal factor that determines skin color is melanin, a natural skin pigment. Melanin is synthesized in the melanosome of melanocytes in the basal layer of the epidermis and moves to the epidermal keratinocytes through the dendrites to determine the color of the skin. It protects the skin from ultraviolet rays or external stimulants . However, excessive accumulation of melanin pigment causes hyperpigmentation phenomenon such as spots, freckles, and skin spots, and shows a negative function in terms of beauty such as promoting aging of the skin. In addition, And the like.

When melanocytes are exposed to exogenous and endogenous factors such as ultraviolet light, drugs or α-MSH, tyrosine, which is a kind of amino acid, is hydroxylated by catalysis of tyrosinase to form 3,4-dihydroxyphenylalanine (DOPA ), And again DOPA is oxidized by tyrosinase to become dopaquinone (DOPA-quinone) to form melanin pigment in two directions. First, the pathway in which black and brown eumelanin pigments are produced is that DOPA-quinone is converted to DOPA-chrome and DOPA-chrome is converted to TRP-2 (DOPA-chrome) DOPAchrome tautomerase was converted to DHICA (5,6-dihydroxyindole-2-carboxylic acid) and converted to indole-5,6-quinone-2-carboxylic acid by TRP-1 (DHICA oxidase) to produce eumelanin (DOPA-chrome) is converted to indole-5,6-quinone by tyrosinase action after autoxidation and conversion to DHI (5,6-dihydroxyindole) Sometimes melanin (eumelanin) is produced. Second, the pathway in which yellow or red pheomelanin pigment is produced is that DOPA-quinone is converted to cystenyl-DOPA by the action of cysteine and glutathione and is converted into enzothiazine alanine It is the pathway that produces pheomelanin as it is converted.

Melanin is synthesized through several intracellular signaling pathways: cyclic adenosine monophosphate (cAMP) / PKA (protein kinase A), protein kinase C (PKC) pathway, and p38 MAP kinase pathway have. Among them, the cAMP / PKA pathway is the main pathway of melanogenesis. When the skin is exposed to UV, the intracellular cAMP concentration is increased, the PKA molecule is activated, and the cAMP response element binding protein (CREB ) To increase the expression of MITF. MITF is an important transcriptional regulator in the melanin synthesis process and promotes the expression of tyrosinase, TRP-1, and TRP-2.

At present, raw materials used as whitening agents include arbutin, ascorbic acid, hydroquinone and the like, but use only a limited amount because of problems including skin safety and formulation stability. Recently, studies on the whitening mechanism and whitening efficacy of natural and herbal medicinal plants harmless to human body and high in stability have been actively conducted.

Peach ( Prunus persica L. Batsch) is a fruit of the peach tree belonging to Rosaceae and is a typical summer fruit. Its main components are water and sugar, and contains organic acids such as tartaric acid, malic acid and citric acid. It also contains esters and alcohols such as malic acid, formic acid, acetic acid and tartaric acid, aldehydes and pectin. Flesh contains a lot of free amino acids, especially aspartic acid content. Peaches account for 8% of the total fruit production in Korea and 6th in the domestic fruit production. However, in order to increase the quality of fruit, the peach grows fruit in the process of cultivation and performs the work which keeps a certain number of fruit within one branch three to four times from the beginning of April to the beginning of May every year, The peach infestation (Yukwa, Yuka, Yukin, etc), which accounts for more than 90% of all fruits, is being abolished.

In addition to fruits, peach seeds are used as herbal medicines for various physiological and pharmacological activities such as menstrual irregularities, dark circles, and genomes. In addition to fruit, , Cough, headache, bronchitis and the like have been used as traditional medicines. However, studies on efficacy have been limited in the case of immature fruits that are discarded.

Therefore, the present inventors have studied various physiological activities from the peach immature field as part of research for exploiting the use of the immature peach which has been discarded in the process of the invention, and by confirming the excellent skin whitening effect from the peach immature and extract, It was completed.

KR 10-107678 B KR 10-179331 B

It is an object of the present invention to provide a cosmetic composition, a food composition and a pharmaceutical composition for inhibiting pigmentation which comprise an immature peach and an extract having an activity of whitening as an active ingredient.

To achieve the above object, the present invention provides a cosmetic composition comprising an immature peach and an extract as an active ingredient.

The composition may be for skin whitening.

The extract may be extracted with any one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and a combination thereof.

The peach immature and extract may have a whitening activity through inhibition of tyrosinase activity.

The extract may be peach immature and hot water extract.

The composition may be in the form of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, pack, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray Lt; / RTI >

The present invention also provides cosmetics having any one of the formulations selected from the group consisting of liposomes and extracts as active ingredients, lotions, essences, skins, lotions, creams and packs.

The present invention also provides a food composition comprising an immature peach and an extract as an active ingredient.

The extract may be extracted with any one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and a combination thereof.

The present invention also provides a health functional food for skin whitening comprising the above food composition.

The present invention also provides a pharmaceutical composition for the prevention or treatment of pigmentation diseases comprising immature peach and extract as an active ingredient.

The pigmentation disorders may include freckles, senile spots, chloasma, spots, brown or black spots, daylight pigment spots, cynic melisma, hyperpigmentation after drug use, gravidic chloasma, Hyperplasia and post-inflammatory hyperpigmentation due to wound or dermatitis.

The extract of the present invention has an effect of inhibiting the enzymatic activity of tyrosinase without exhibiting cytotoxicity and effectively inhibiting the expression of melanin biosynthesis and genes associated therewith and thus being useful for preventing or treating skin whitening and pigmentation In addition to being usable for a long time, it is extracted from plants used for edible purposes, unlike artificially synthesized compounds, no adverse effects are posed and safety is also recognized, so that not only a pharmaceutical composition such as a cosmetic composition for developing cosmetics, And the like.

FIG. 1 is a graph showing the results of inhibition of melanin formation by hot water extracts according to an embodiment of the present invention, wherein the horizontal axis represents each treatment group, and the vertical axis represents the relative value of the melanin content to the control group. Arbutin was treated with arbutin, PUP-HW was treated with peach immature and hydrothermal extract, PHP-HW was treated with peach maturation and hot water extract, PL-HW was treated with peach leaf hydrothermal extract and PB-HW was treated with peach hydrothermal extract Respectively.
FIG. 2 is a graph showing the cell survival rate of each solvent extract according to an embodiment of the present invention. The horizontal axis represents each treatment group, and the vertical axis represents cytotoxicity. 0 / IBMX- is a control group, 0 / IBMX + is a control group treated only with IBMX, Arbutin // IBMX + is an arbutin treatment group, HW / IBMX + is a peach immature and hot water extract treatment group, E50 / IBMX + Treated group, E100 / IBMX + treated with peach immature and 100% ethanol extract treated group, M50 / IBMX + treated with peach immature and 50% methanol extract, and M100 / IBMX + treated with peach immature and 100% methanol extract treated group.
FIG. 3 is a graph showing the results of tyrosinase inhibition activity of the solvent extract according to an embodiment of the present invention, wherein the horizontal axis represents each treatment group, and the vertical axis represents tyrosinase activity. 0 / IBMX- is a control group, 0 / IBMX + is a control group treated only with IBMX, Arbutin // IBMX + is an arbutin treatment group, HW / IBMX + is a peach immature and hot water extract treatment group, E50 / IBMX + Treated group, E100 / IBMX + treated with peach immature and 100% ethanol extract treated group, M50 / IBMX + treated with peach immature and 50% methanol extract, and M100 / IBMX + treated with peach immature and 100% methanol extract treated group.
FIG. 4 is a graph showing the results of inhibition of melanin formation by the solvent extract according to an embodiment of the present invention, wherein the horizontal axis represents each treatment group, and the vertical axis represents the relative value of the melanin content to the control group. 0 / IBMX- is a control group, 0 / IBMX + is a control group treated only with IBMX, Arbutin // IBMX + is an arbutin treatment group, HW / IBMX + is a peach immature and hot water extract treatment group, E50 / IBMX + Treated group, E100 / IBMX + treated with peach immature and 100% ethanol extract treated group, M50 / IBMX + treated with peach immature and 50% methanol extract, and M100 / IBMX + treated with peach immature and 100% methanol extract treated group.
FIG. 5 is a graph showing the results of tyrosinase inhibition activity extracted from a B16 / F10 cell of a hot-water extract according to an embodiment of the present invention, wherein the horizontal axis represents each treatment group, the vertical axis represents tyrosinase activity, Control group was the control group, Kojic acid was the kojic acid treatment group, Arbutin was the arbutin treatment group, and PUP-HW was the peach immature and hot water extract treatment group.
6 is a graph showing the results of confirming the inhibitory activity of tyrosinase mRNA expression of the extract. Each treatment group on the horizontal axis of the graph was treated with control (DW, IBMX-), IBMX control (IBMX control), positive control group arbutin / IBMX +, peach immature and hot water extract treatment group -HW / IBMX +).
FIG. 7 is a graph showing the results of confirming the activity of inhibiting the expression of TRP-1 mRNA in the hot-water extract. FIG. Each treatment group on the horizontal axis of the graph was treated with control (DW, IBMX-), IBMX control (IBMX control), positive control group arbutin / IBMX +, peach immature and hot water extract treatment group -HW / IBMX +).
Fig. 8 shows the expression of TRP-2 and mRNA in the hot-water extract. Each treatment group on the horizontal axis of the graph was treated with control (DW, IBMX-), IBMX control (IBMX control), positive control group arbutin / IBMX +, peach immature and hot water extract treatment group -HW / IBMX +).
9 is a graph showing the inhibitory activity of MITF mRNA expression of the hot-water extract. Each treatment group on the horizontal axis of the graph was treated with control (DW, IBMX-), IBMX control (IBMX control), positive control group arbutin / IBMX +, peach immature and hot water extract treatment group -HW / IBMX +).

The present invention provides a cosmetic composition comprising an immature peach and an extract as an active ingredient.

The peach immature and extracts can effectively inhibit melanin synthesis and tyrosinase activity, thus exerting an effect on skin whitening.

The peach ( Prunus persica L.) is a fruit of the peach tree belonging to Rosaceae, and the above-mentioned peach immature fruit means all the fruit of maturity and mature fruit during the growth stage of the fruit, and specifically, the fruit quality and yield (Fruit thinning), a young fruit, which means fruit from the end of fertilization to the stage before the fruit is bloomed, and a fruit drop from the plant before the fruit has matured. .

The immature part refers to flesh in which seeds have been removed, and the dried or non-dried peach immature part may be used in the preparation of the composition. For the extraction efficiency, the immature part can be minced and used. It was experimentally confirmed that the effect of inhibiting the synthesis of melanin in the case of the peach immature and extracts was remarkably superior to that of other parts of the peach (for example, leaves, branches, etc.), particularly peach maturity and extract.

The composition may be a cosmetic composition comprising an immature peach extract and an extract as an active ingredient, which may be used for skin whitening and, in other words, has whitening activity.

The extract may have a whitening activity through inhibition of tyrosinase activity, or may have a whitening activity through melanin inhibition. And preferably have a whitening activity by the complex effect of the action.

The whitening means a method of increasing the brightness of the skin with reduced brightness due to excessive pigment such as melanin, a method of maintaining the brightness of the skin at a certain level, and a skin having increased brightness formed by the method.

The melanin inhibition may not only inhibit the synthesis of melanin, but may also include both inhibition of melanin that has been previously produced and inhibition of the expression of genes associated therewith.

The extract can be prepared by extracting with an extraction solvent or extracting with an extraction solvent and fractionating the extract with a fraction solvent.

The extraction solvent may be at least one selected from the group consisting of water and an organic solvent. The organic solvent may be a polar solvent such as an alcohol having 1 to 4 carbon atoms such as methanol or ethanol, ethyl acetate or acetone, a nonpolar solvent such as benzene, hexane or dichloromethane, or a mixed solvent thereof, preferably water, To 4, and a combination thereof. More preferably, the solvent may be water. In the most preferred form, hot water may be used as an extraction solvent. When the hot water was used as the extraction solvent, it was experimentally confirmed that the melanin synthesis inhibitory effect was superior to that of the other extract solvent.

The extraction solvent may be used in an amount of 1 to 20 times, preferably 7 to 13 times, more preferably 9 to 11 times the immature and weight.

The extract may be filtered, concentrated and / or dried to remove the solvent. Specifically, the filtration may be performed using a pressure-reducing filter or a filter paper. The concentration may be carried out by using a vacuum concentrator. The drying may be performed by a freeze-drying method, but the present invention is not limited thereto. Any conventional apparatus and techniques that can be used for extraction or fractionation can be used.

The extract may be one prepared by a conventional method for producing an extract. More specifically, the method may be carried out by adding an extraction solvent to the immature organs after removal of the impurities and performing an extraction process. The extraction process may be a cold extraction method, a warm extraction method, a pressure extraction method, or an ultrasonic pulverization extraction method.

The extract is preferably prepared under the following extraction conditions, but is not limited thereto. The extraction time of the extract may be performed for 1 hour to 10 hours, preferably 5 hours to 8 hours, and the extraction temperature may be 10 ° C to 100 ° C, preferably 60 ° C Deg.] C to 80 < 0 > C. In the case of the extract obtained by the above method, the whitening effect is excellent, so that it can be usefully used as a cosmetic composition.

The cosmetic composition may be in the form of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, pack, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray It can be one. The cosmetic composition may further comprise ingredients conventionally used according to the formulation.

The cosmetic composition may be prepared in various forms according to the conventional cosmetic preparation method using the immature peach extract and extract of the present invention and may further include components commonly used in the field of cosmetic compositions, , Wetting agents, emollients, surfactants, stabilizers, solubilizers, vitamins, pigments, ultraviolet absorbers, purified water and corymbroses.

The cosmetic composition may contain 0.001 to 50% by weight of the extract of the present invention relative to the whole composition. When the extract is contained at the above concentration, it does not show cytotoxicity and can have a safe and excellent whitening effect.

The present invention also provides cosmetics having any one of the formulations selected from the group consisting of liposomes and extracts as active ingredients, lotions, essences, skins, lotions, creams and packs.

Examples of the cosmetics include a skin, a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, a nutrition cream moisturizer cream, a hand cream, a foundation, an essence, a nutrition essence, Foam, cleansing lotion, cleansing cream, body lotion and body cleanser, but is not limited thereto.

The present invention also provides a food composition comprising peach immature and extract as an active ingredient, and a health functional food for skin whitening comprising the food composition.

The extract may be extracted with any one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and a combination thereof.

The extract is preferably extracted with hot water, and the extract extracted with the hot-water extract is superior in safety and remarkably superior in the effect of inhibiting tyrosinase activity than in the case of using a solvent, A whitening effect can be exhibited.

The term "food" means a natural or processed product containing one or more nutrients. Preferably, the food refers to a state in which the food can be directly eaten through a certain degree of processing. In general terms, Functional foods, beverages, food additives and beverage additives.

The food may be, for example, various foods, beverages, gums, tea, a vitamin complex, a health functional food, and the like. In addition, in the present invention, the food may contain special nutritional foods (e.g., crude oil, spirits, infant food, etc.), meat products, fish products, tofu, jelly, noodles (Such as soy sauce, soybean paste, hot pepper paste, mixed sauce), sauces, confectionery (eg snacks), dairy products (eg fermented milk, cheese), other processed foods, kimchi, pickled foods (E.g., fruit and vegetable beverages, two oils, fermented beverages, etc.), natural seasoning (e.g., ramen soup, etc.).

The food, the functional food, the health functional food, the beverage, the food additive and the beverage additive can be produced by a usual production method.

In the present invention, the health functional food refers to a food group imparted with added value to function or express the function of the food by physical, biochemical, biotechnological techniques, etc., or to control the biological defense rhythm of the food composition, Means a food which is processed and designed so that the body control function related to restoration and the like is sufficiently expressed to the living body.

The health functional food may include food-acceptable food supplementary additives, and may further include suitable carriers, excipients and diluents conventionally used in the production of health functional foods.

In the present invention, beverage means a general term for drinking or enjoying a taste, and is intended to include a health functional beverage.

The above-mentioned beverage is not particularly limited as long as it contains the above-mentioned extract as an active ingredient as an essential ingredient at the indicated ratio, and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages.

Examples of the natural carbohydrates include polysaccharides such as disaccharides such as monosaccharides such as glucose and fructose, maltose and sucrose, dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol . The flavor may be a natural flavor such as tautatin or a stevia extract such as rebaudioside A or glycyrrhizin or a synthetic flavor such as saccharin, aspartame and the like.

The amount of the natural carbohydrate to be added may generally be about 1 to 20 g, preferably 5 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 production of natural fruit juice, fruit juice drink, and vegetable drink.

In addition to the above, the food composition of the present invention can be used as a flavoring agent such as a variety of nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate etc.), pectic acid and its salts, Salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like.

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

The health-functional beverage is used to control the bio-defense rhythm of the beverage group or beverage composition to which the added value is imparted so that the function of the beverage functions for a specific purpose by physical, biochemical, biotechnological, or the like, Means a beverage which has been designed so as to sufficiently express the body controlling function related to the living body.

The health functional beverage is not particularly limited to the ingredients other than the peach immature and extract of the present invention as essential ingredients in the indicated ratios and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages have.

Examples of the natural carbohydrates include polysaccharides such as disaccharides such as monosaccharides such as glucose and fructose, maltose and sucrose, dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol . The flavor may be a natural flavor such as tautatin or a stevia extract such as rebaudioside A or glycyrrhizin or a synthetic flavor such as saccharin, aspartame and the like.

The amount of the natural carbohydrate to be added may generally be about 1 to 20 g, preferably 5 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 production of natural fruit juice, fruit juice drink, and vegetable drink.

In addition to the above, the food composition of the present invention can be used as a flavoring agent such as a variety of nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate etc.), pectic acid and its salts, Salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. These components can be used independently or in combination. The proportion of such additives is not critical, but may be selected in the range of 0 to 20 parts by weight per 100 parts by weight of the peach immature and extract of the present invention.

The health functional foods may further contain food additives and the suitability as a food additive may be determined according to the General Rules for Food Additives approved by the Food and Drug Administration, Judge by standards.

The extract of the present invention, which is added to foods containing beverages in the process of producing the health functional food of the present invention, can suitably increase or decrease its content as required, and is preferably 1 to 15 wt% As shown in Fig.

The present invention also provides a pharmaceutical composition for the prevention or treatment of pigmentation diseases comprising immature peach and extract as an active ingredient.

The peach immature and extracts can effectively inhibit melanin synthesis and related gene activity in the skin and inhibit tyrosinase activity when the pigment is applied to the over-deposited skin, thereby effectively preventing diseases and lesions related to pigment deposition , Ameliorated or treated (removed).

The pigmentation disorder refers to any disease associated with symptoms that the pigment is excessively proliferating or depositing, and is preferably selected from the group consisting of freckles, senile spots, chloasma, spots, brown or black spots, cynic melisma), hyperpigmentation after drug use, gravidic chloasma, skin pigment hyperplasia, and hyperpigmentation after inflammation due to wound or dermatitis.

The pharmaceutical composition refers to a medicinal product for diagnosing, treating, alleviating, treating, or preventing disease in an animal including a human being.

The composition for preventing or treating a pigmentation disorder comprising the extract as an active ingredient may contain 0.001% by weight to 99.9% by weight or 0.1% by weight to 99% by weight or 1% by weight to 20% by weight of the extract, based on the total weight of the composition However, the present invention is not limited thereto. Depending on the use of the composition and the method of use, the content of the extract may be suitably adjusted to a pharmaceutically effective amount or a desired amount.

The pharmaceutical composition for preventing or treating a pigmentation disease of the present invention may contain the above-mentioned peach immature and extract alone as an active ingredient, and may be formulated into pharmaceutically acceptable carriers, excipients, diluents And / or a subcomponent.

More specifically, in addition to the above-mentioned active ingredients, there may be further added nutritional agents, vitamins, electrolytes, flavors, coloring agents, aggravating agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, Glycerin, alcohols, carbonating agents used in carbonated drinks, and the like.

The term "pharmaceutically acceptable" as used herein means physiologically acceptable and does not normally cause an allergic reaction such as gastrointestinal disorder, dizziness, or the like when administered to an animal, preferably a human. The pharmaceutically effective amount may be appropriately changed depending on the disease and its severity, the age, body weight, health condition, sex, administration route and treatment period of the patient.

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, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, 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 physiological saline. However, it is not limited thereto, and any conventional carrier, excipient or diluent may be used.

The ingredients may be added to the active ingredient peach immature and extract independently or in combination.

In addition, the pharmaceutical composition for preventing or treating the pigment deposition disease may be a conventional filler, an extender, a binder, a disintegrant, an anticoagulant, a lubricant, a wetting agent, a pH adjuster, a nutrient, a vitamin, an electrolyte, an alginic acid and its salt, , Protective cololide, glycerin, fragrance, emulsifier or preservative, and the like. These components may be added to the pharmaceutical composition for preventing or treating pigmentation diseases of the present invention independently or in combination.

In addition, the pharmaceutical composition for preventing or treating the pigment deposition disease may further comprise a substance showing improvement, relief, treatment or prevention of skin pigmentation in addition to the above-mentioned effective ingredient, May be added in an amount ranging from 0.1 part by weight to 20 parts by weight per 100 parts by weight of the pharmaceutical composition for therapeutic use, or from 5 parts by weight to 200 parts by weight with respect to 100 parts by weight of the extract as an active ingredient.

The method for administering the pharmaceutical composition for preventing or treating the pigment deposition disease may be either oral or parenteral, and may be administered through various routes including oral, transdermal, subcutaneous, intravenous, or muscular.

In addition, the formulations of the compositions may vary depending on the method of use and may be formulated using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to the mammal . Examples of the above-described formulations include granules, powders, syrups, liquids, suspensions, tablets, injections, injectable tablets, cataplasma, capsules, soft gelatine capsules or hard gelatine capsules.

The formulation may further contain an excipient such as an ordinary filler, an extender, a binder, a disintegrant, a surfactant, an anticoagulant, a lubricant, a wetting agent, a flavor, an emulsifier, an antiseptic, a sweetener, a fragrance or a preservative.

In general, solid dosage forms for oral administration include tablets, pills, soft or hard capsules, pills, powders and granules, which may contain one or more Excipients such as starch, calcium carbonate, sucrose or lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.

In addition, liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups. In addition to water or liquid paraffin, which is a commonly used simple diluent, various excipients, for example, Wetting agents, sweetening agents, perfumes, preservatives, and the like.

Examples which may be mentioned for skin administration are suitable for the production of dusting powders, emulsions, suspensions, oils, sprays, ointments, ointments, creams, pastes, gels, foams or solutions, and may be formulated as transdermal therapeutics (TTS) ) And / or excipients. The topical pharmaceutical preparations of the present invention may be semi-solid formulations, in particular ointments (ointments, suspension ointments), creams, gels or pastes. Lactic alcohol, cetyl alcohol, stearyl alcohol, fatty acids such as palmitic acid or stearic acid, liquid or solid paraffin or ozokerite, liquid or solid waxes, for example, For example, isopropyl myristate, natural or partially synthetic fats such as coconut fatty acid triglycerides, hydrogenated oils such as hydrogenated peanut or castor oil, or fatty acid partial esters of glycerol, such as glycerol monostearate or glycerol There is 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 Sterol or polyoxyethylene fatty alcohol ethers or fatty acid esters such as sorbitan oleate and / or sorbitan isostearate, such as, for example, an alkali metal salt of an anionic surfactant, for example a fatty alcohol sulfonate, Such as sodium lauryl sulfate, sodium cetyl sulfate or sodium stearyl sulfate, which are generally used in the presence of the fatty alcohols described above, for example cetyl alcohol or stearyl alcohol. Among them, it is possible to add an agent for preventing the drying of the cream, for example, a polyalcohol such as glycerol, sorbitol, propylene glycol and / or polyethylene glycol to the aqueous phase or to add a preservative, perfume or the like to the aqueous phase.

Furthermore, the compositions of the present invention may be formulated using any suitable method known in the art or using methods disclosed in Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA .

The pharmaceutical preparations of the present invention may be paraffinic, especially low viscosity paraffin, which may be an anhydrous ointment and which is suitable for topical use and is liquid at body temperature, or which contains the natural or partially synthetic fat, for example coconut fatty acid triglycerides Sorbitan monostearate and distearate, silicones such as polymethylsiloxane, such as hexamethyldisiloxane, or octamethyl triisostearate, such as, for example, glycerol monostearate and distearate, Siloxanes, and may contain, for example, fatty alcohols associated with aqueous creams and increasing water absorption capacity, and sterols, wool waxes, other emulsifiers and / or other additives.

The dosage of the composition can be suitably determined by those skilled in the art in consideration of the administration method, age, sex and weight of the individual, severity of disease, condition, absorption of the active ingredient in the body, inactivity and the drugs to be used together. For example, when the active ingredient of the composition is used as a reference, the peach immature extract and the extract have a composition of 0.0001 mg / kg body weight to 500 mg / kg body weight, 0.01 mg / kg body weight to 400 mg / kg body weight, (Body weight) or 1 mg / kg (body weight) to 300 mg / kg (body weight), and may be administered once a day or divided into several times. However, the dosage is not limited in any way to the scope of the present invention.

In addition, the pharmaceutical composition of the present invention can be used alone for improving, alleviating, treating or preventing skin pigmentation, or in combination with methods using surgery, hormone therapy, drug therapy and biological response modifiers.

The numerical values set forth herein should be construed to cover equivalent ranges unless otherwise indicated.

Best Mode for Carrying Out the Invention Hereinafter, preferred examples and formulation examples are shown to facilitate understanding of the present invention. However, the following examples and preparations are provided only for the purpose of easier understanding of the present invention, and the contents of the present invention are not limited by the examples or preparation examples.

[ Example ]

Production Example 1 . Preparation of immature and extract

The samples used in the present invention were immature (including red, brown and white) produced in the town of Sejong Special Self-governing Provincial Government and were washed and dried, Followed by reflux extraction at 70 ° C for 6 hours. 50% ethanol, 100% methanol, 50% methanol and 100% methanol were used as the extraction solvent. The obtained extract was filtered, concentrated under reduced pressure using a rotary evaporator at 50 ° C, and lyophilized to obtain an extract Respectively. The peach immature and extracts were then used in the experimental examples.

Experimental Example  1. Identification of Melanogenesis Inhibitory Effect of Peach Extracts

Peach immature, peach maturation, peach leaf and peach branches were prepared to examine melanin inhibitory effect of the extract of each part of peach, and hot water extract was prepared in the same manner as in Preparation Example 1, and each extract treatment The experiment was divided into two groups.

3-isobutyl-1-methylxanthine (IBMX) was treated to determine melanin content in B16 / F10 cells induced melanogenesis. B16 / F10 cells were inoculated into 6 well-plates at a concentration of 1 × 10cells / well in DMEM supplemented with 10% fetal bovine serum (FBS) and cultured in a CO ₂ incubator at 37 ° C for 24 hours. The crude medium was removed, and the peach extract was treated with DMEM medium supplemented with 10% FBS at a concentration of 1.0 mg / mL and cultured in a CO ₂ incubator at 37 ° C for 48 hours. The pretreatment group except for the control without treatment of the extract was treated with 0.1 mM of IBMX to induce melanin biosynthesis. Arbutin, a substance with a whitening effect, was used as a positive control and treated at a concentration of 0.1 mg / mL. After 48 hours, the cells of each well were washed twice with cold PBS, and cells were recovered using a cell scraper. Then, 20 mmol / L Tris-0.1% Triton X-100 (pH 7.5) was added And vortexing for 30 minutes to extract melanin. After centrifugation at 12,000 rpm at 4 ° C for 10 minutes, 150 μL of 1 N NaOH containing 10% DMSO (dimethyl sulfoxide) was added to the pellet, followed by heating at 80 ° C for 30 minutes. The reacted mixture was dispensed into 96-well plates in an amount of 100 μL, and the absorbance was measured at 415 nm using a microplate reader. The results were calculated according to the following formula, and the results are shown in FIG.

[formula]

Melanin content (%) = (absorbance of sample treated group / absorbance of control group) x 100

As shown in Fig. 1, when the melanin content of the control not treated with the sample was compared to 100%, the melanin content of the control group treated with IBMX alone (IBMX control) was 208% And the melanin content of the arbutin-treated group was 114%, which was 94% lower than that of the IBMX control group. Melanin contents in the peach extract-treated group were about 133% (75% inhibition of melanin production compared to the IBMX control) in peach immature and hot-water extract treated group (PUP-HW), peach maturation and hydrothermal extract treatment group -HW), about 163% (44% inhibition of melanin production compared to the IBMX control) in peach leaf hydrothermal extract treated group (PL-HW), and about 150% 175% (33% inhibition of melanogenesis compared to the IBMX control) in the PB-HW group. The results showed that all the extracts of peaches inhibited melanogenesis in the cells. Among them, the melanin biosynthesis inhibitory activity was about 20% higher than that of other extracts of peach, Were used to perform additional whitening activity experiments.

Experimental Example  2. By extraction solvent  Evaluation of cytotoxicity of extracts

The cell viability was measured to confirm the cytotoxicity of the five extracts extracted in the above production examples. For this purpose, murine melanoma cells, a melanocyte derived from mice, were cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS) at a concentration of 1 × 10 ⁴ cells / well at 96 well plate and cultured in a CO ₂ incubator at 37 ° C for 24 hours. The crude medium was removed and the immature peach and five samples of the extract were treated with DMEM medium containing no serum at concentrations of 0.01, 0.1 and 1.0 mg / mL, respectively, and incubated at 37 ° C in a CO2 incubator And cultured for 24 hours. In order to induce melanogenesis, 0.1 mM 3-isobutyl-1-methylxanthine (IBMX) was added to all treatments except for the control without treatment of the extract Respectively. Arbutin, a well known substance for whitening effect, was used as a positive control and treated at a concentration of 0.1 mg / mL. After 24 hours, the medium was removed for measurement of cell viability and 100 μL of MTT solution (3- (4,5-dimethylthiazol-2yl) -2,5-diphenyl-2H-tetrazolium bromide) The medium was removed. The absorbance was measured at 540 nm using a microplate reader (Model 680 microplate reader, Bio-Rad, USA) after dissolution of intracellular formazan into dimethyl sulfoxide (DMSO) The calculation was carried out according to the formula 1, and the results are shown in Fig.

[Equation 1]

Cell survival rate (%) = (absorbance of sample treated group / absorbance of control group) x 100

As shown in Fig. 2, when the cell survival rate of the control without treatment with the extract was 100%, the cell survival rate of the IBMX control treated group (IBMX control) and the positive control group arbutin treated group Respectively. The cell survival rate of HW was 95%, 100% and 100%, respectively, and the cell viability of the 50% ethanol extract group (E50) was 104% , Cell viability was 95%, 95%, 100%, 100%, 103% and 100% ethanol extract treated group (E100) The cell viability of 100% methanol extract (M100) was 101%, 98% and 97%. Based on the above results, it was confirmed that the peach immature and solvent extracts were not toxic to B16 / F10 cells at a concentration of 1.0 mg / mL or less.

Experimental Example  3. Determination of tyrosinase inhibitory activity of solvent extracts

The tyrosinase inhibitory activity was measured at the in vitro level to examine the whitening activity of the five extracts extracted in the above Preparation Example.

The mushroom-derived tyrosinase (tyrosinase, 150 units, Sigma, USA) was used to measure DOPA chrome produced as a result of tyrosinase action by colorimetry, 10 mM diphenylalanine (3,4-dihydroxy-L-phenyl-alanine, Sigma, USA) was used as the substrate. The concentrations of the samples were adjusted to 0.01, 0.1 and 1.0 mg / mL, and the positive control kojic acid was adjusted to 0.05 mg / mL. 100 μL of 150 U tyrosinase was added to a reaction mixture containing 550 μL of distilled water, 50 μL of potassium phosphate buffer (KPB, pH 6.8) and 100 μL of 1 M potassium phosphate buffer For 2 minutes. Blank was supplemented with 50 mM KPB buffer (enzyme diluent) instead of tyrosinase. To this mixture, 200 μL of 10 mM DOPA solution was added and reacted at 37 ° C. for 10 minutes. After the reaction mixture was stopped in an ice bath, the amount of DOPA chrome produced was measured at 475 nm using a spectrophotometer. The activity of tyrosinase was calculated according to the formula 2, and the results are shown in Fig.

[Equation 2]

mushroom tyrosinase activity (%) = (Sample O.D - Blank O.D / Control O.D - Blank O.D) x 100

As shown in Fig. 3, when the activity of the control without treatment of the sample was taken as 100%, the tyrosinase activity of the positive control was 34%, the tyrosinase inhibitory activity of about 66% Respectively. In the case of the peach immature and extract treatment groups, about 103%, 98%, and 100% of the ethanol extract treatment group (E50) were treated in the hot water extract treatment group (HW) 100% methanol extract treatment group (95%, 100% ethanol extract treated group (E100)) in about 99%, 95%, 84% and 50% methanol extract treated group M100) showed about 101%, 95%, and 84% tyrosinase activity. From the above results, it was experimentally confirmed that peach immature and 1.0% ethanol / water extract, 100% ethanol extract and 100% methanol extract had tyrosinase inhibitory activity of about 16%, respectively.

Example  4. Examination of inhibitory effect of melanin on the extract

Melanin content was measured in B16 / F10 cells induced by melanin production by treating 3-isobutyl-1-methylxanthine (IBMX) in order to examine the inhibitory effect of 5 kinds of extracts extracted from the above-mentioned production examples.

B16 / F10 cells were inoculated into 6 well-plates at a concentration of 1 × 10cells / well in DMEM supplemented with 10% fetal bovine serum (FBS) and cultured in a CO ₂ incubator at 37 ° C for 24 hours. The medium was removed and the extracts were treated with 0.01%, 0.1, 1.0 mg / mL of the peach immature extract and the DMEM medium supplemented with 10% FBS, and cultured in a CO ₂ incubator at 37 ° C for 48 hours. The pretreatment group except for the control without treatment of the extract was treated with 0.1 mM of IBMX to induce melanin biosynthesis. Arbutin, a substance with a whitening effect, was used as a positive control and treated at a concentration of 0.1 mg / mL. After 48 hours, the cells of each well were washed twice with cold PBS, and cells were recovered using a cell scraper. Then, 20 mmol / L Tris-0.1% Triton X-100 (pH 7.5) was added And vortexing for 30 minutes to extract melanin. After centrifugation at 12,000 rpm at 4 ° C for 10 minutes, 150 μL of 1 N NaOH containing 10% DMSO (dimethyl sulfoxide) was added to the pellet, followed by heating at 80 ° C for 30 minutes. The reacted mixture was dispensed into 96-well plates in an amount of 100 μL each, and the absorbance was measured at 415 nm using a microplate reader. The results were calculated according to Equation 3, and the results are shown in FIG. 4 .

[Equation 3]

Melanin content (%) = (absorbance of sample treated group / absorbance of control group) x 100

As shown in Fig. 4, when the melanin content of the control without the sample was compared to 100%, the melanin content of the control group treated with IBMX alone (IBMX control) was 233% And the melanin content of the arbutin-treated group was 98%, which was 135% lower than that of the IBMX control group. In the case of the peach immature and extract treatment groups, about 193%, 174%, and 20% respectively in the hot water extract treatment group (HW) and the ethanol treated group (E50) (M50) treated with about 200%, 200%, 201%, 166% and 50% methanol extracts treated with 170% and 100% ethanol extracts M100) showed melanin contents of about 197%, 193%, and 166%. In the case of treatment with 1.0 mg / mL of the concentrate, about 92%, 63%, 67%, 77% and 67% of the above-mentioned solvents were inhibited, And the melanin production inhibitory activity of the hydrothermal extract was highest among the five kinds of extracts. Therefore, additional whitening activity tests were conducted using the extracts.

Example  5. Heat number  Measurement of tyrosinase inhibitory activity of B16 / F10 cell-derived extracts

To investigate the whitening activity of peach immature and hot - water extracts at the cellular level, enzymatic activity was measured using Murine tyrosinase from B16 / F10 cells. The tyrosinase was extracted from the B16 / F10 cell line which was induced by melanin production by treating with IBMX.

More specifically, the B16 / F10 cell line was inoculated into 6 well-plates at a concentration of 1x10 cells / well using DMEM supplemented with 10% fetal bovine serum (FBS) and cultured in a CO ₂ thermostat at 37 ° C for 24 hours. The medium was removed and 300 μL of 100 μM IBMX was treated with DMEM medium supplemented with 10% FBS and cultured at 37 ° C. in a CO ₂ incubator for 48 hours. After 48 hours, the cells were washed twice with cold PBS, the cells were recovered using a cell scraper, 20 mmol / L Tris-0.1% Triton X-100 (pH 7.5) The cells were lysed by vortexing and centrifuged at 12,000 rpm at 4 ° C for 10 minutes. The supernatant was recovered and used as a tyrosinase enzyme solution derived from B16 / F10 cells. The enzyme activity was assayed for tyrosinase activity according to the method described in Experimental Example 2, and the results are shown in Fig.

As shown in FIG. 5, kojic acid had a inhibitory activity of 56% and arbutin had a 17% inhibitory activity when the enzyme activity of the control without the sample was taken as 100% Respectively. The enzymatic activities of the peach immature and hot water extracts were significant at the concentrations of about 89%, 86%, and 78%, respectively, in the order of the above-mentioned concentrations. In the 1.0 mg / mL treated group, the B16 / F10 cell- And about 22% inhibitory activity against the enzyme.

Experimental Example  6. Peach Immature Heat number  Measurement of inhibitory effect of melanin biosynthesis-related genes on the expression of extracts

In order to investigate the inhibitory effects of tyrosinase, TRP-1, TRP-2 and MITF, which are key genes involved in melanin biosynthesis, in order to examine the effect of melanin biosynthesis inhibition of peach immature and hot water extracts, transcription-PCR (RT-PCR). B16 / F10 cells were inoculated into 6 well-plates at a concentration of 1 × 10cells / well using DMEM supplemented with 10% fetal bovine serum (FBS) and cultured in a CO ₂ incubator at 37 ° C for 24 hours. The medium was removed and the immature and hot water extracts of peach were treated with 1.0 mg / mL of DMEM supplemented with 10% FBS and cultured in a CO ₂ incubator for 48 hours. The pretreatment group except for the control without treatment was treated with 0.1 mM of IBMX to induce melanin production and positive control was treated with 0.1 mg of arbutin, / mL < / RTI > After RNA extraction, cDNA was synthesized and RT-PCR was performed to confirm the expression level of each gene from the synthesized cDNA. The synthesized cDNA (template DNA), Taq DNA polymerase, dNTP, 10X PCR buffer and forward / reverse primers of each gene were mixed and PCR was carried out as follows. After 5 minutes of reaction at 95 ° C, denaturation at 95 ° C for 30 seconds, annealing at 54 ° C for 30 seconds, and extension at 72 ° C for 30 seconds were carried out for 45 cycles, followed by extension at 72 ° C for 7 minutes. The PCR product was isolated by electrophoresis on a 2.5% agarose gel with 0.002% ethidium bromide according to the size of the gene. The expression level of the gene was confirmed by ultraviolet light and β-Actin was used as a reference material. The strength was analyzed and quantified, and the results are shown in Figs. 6 to 9. Fig.

As shown in FIG. 6, when the expression level of tyrosinase mRNA in the control group (control, DW / IBMX-) without treatment with the extract was 100%, the expression level of the control group (IBMX control, DW / IBMX + The expression level of arbutin / IBMX + was 227%, and the expression level was 36% lower than that of the IBMX control. The expression level of arbutin / IBMX + was 263%, 163% The expression of PUP-HW / IBMX + in peach immature and hot-water extracts was 208%, which was about 55% higher than tyrosinase mRNA expression in the IBMX control.

In FIG. 7, when the TRP-1 mRNA expression level of the control (DW, IBMX-) was 100%, the expression level of the control group treated with IBMX alone (IBMX control, DW / IBMX +) was 206% (arbutin / IBMX +) in the positive control group was 137% and the expression level was 69% lower than that of the control group (control, DW / IBMX-). The expression level of PUP-HW / IBMX + in the immature and hot water extracts of peach was 149%, which was about 57% higher than that of the IBMX control, indicating that TRP-1 mRNA expression was inhibited.

In FIG. 8, when the expression level of TRP-2 mRNA in the control (control, DW / IBMX-) was 100%, the expression level of the control group treated with IBMX alone (IBMX control, DW / IBMX +) was 173% (arbutin / IBMX +) expression was 132% and the expression level was decreased by 40% as compared with the IBMX control, compared with control (DW / IBMX-). The expression level of PUP-HW / IBMX + in peach immature and hot water extracts was 156%, which was about 17% inhibition of TRP-2 mRNA expression compared to the IBMX control.

In FIG. 9, the expression level of the control MITF mRNA was 100%, and the expression level of the control group (IBMX control, DW / IBMX +) treated with IBMX alone was 198%, compared with the control (control, DW / IBMX-) Expression was increased by 98% and expression of arbutin / IBMX + in the positive control group was 154%, which was 44% lower than that of the IBMX control. The expression of PUP-HW / IBMX + in the immature and hot water extracts of peach was 138%, which was about 60% higher than that of the IBMX control.

From these results, it was confirmed that melanin biosynthesis was reduced by inhibiting melanin biosynthesis expression of peach immature and hydrothermal extracts.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, Of the right.

Claims (12)

A cosmetic composition comprising an immature peach and an extract as an active ingredient. The method according to claim 1,
Wherein the composition is for skin whitening. The method according to claim 1,
Wherein the extract is extracted with any one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and a combination thereof. The method according to claim 1,
Wherein the peach immature extract and the extract have a whitening activity through inhibition of tyrosinase activity. The method according to claim 1,
Wherein the extract is an immature and hot water extract of peach. The method according to any one of claims 1 to 5,
The composition may be in the form of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, pack, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray Composition. A cosmetic having any one of the formulations selected from the group consisting of lotions, essences, skins, lotions, creams, and packs containing the extract according to any one of claims 1 to 5 as an active ingredient. A food composition comprising peach immature and extract as active ingredients. 9. The method of claim 8,
Wherein the extract is extracted with any one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and a combination thereof. A health functional food for skin whitening comprising the food composition according to claim 8 or 9. A pharmaceutical composition for the prevention or treatment of pigmentation diseases comprising immature peach and extract as an active ingredient. 12. The method of claim 11,
The pigmentation disorder is caused by freckles, senile spots, liver, spots, brown or black spots, daylight pigmentation, cynic melisma, hyperpigmentation after drug use, gravidic chloasma and scarring or dermatitis Hyperpigmentation after inflammation, and hyperpigmentation after inflammation.

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