KR20170073308A - Composition for improving the skin - Google Patents

Abstract

The present invention relates to a composition comprising salvianolic acid A as an active ingredient, and the composition of the present invention has an effect of improving or preventing skin aging, wrinkles, reduced elasticity and moisture content, (Type I) and sulfosuccinic acid glycosaminoglycans and to increase the expression of HAS-2 and HAS-3 to fundamentally improve and prevent skin wrinkles, aging, elasticity, etc., And can be usefully used as a composition for improving cosmetics, improving skin wrinkles, promoting moisturizing, and whitening.

Description

[Composition for improving the skin]

The present invention relates to a composition effective for improving wrinkles, elasticity, moisturizing and whitening of the skin.

The skin is an important body which is responsible for various physiological functions such as a function for protecting the human body from the external environment, a barrier function for preventing the internal moisture and useful components from flowing out, a temperature control function, and an excretion function. As the aging of an individual progresses, the skin is also aged to lose this important function. In general, the main causes of skin aging are largely divided into extrinsic factors such as intrinsic factors explained by the increase in natural age and sunlight damage have. As a result of skin aging caused by these internal and external factors, wrinkle formation and elasticity decrease phenomenon are caused mainly due to damage and change of the dermal layer.

The structure of the skin is largely divided into the epidermal layer, the dermal layer, and the subcutaneous fat layer. The dermis is a substantial skin that makes up 90% of the skin and consists of a matrix that fills the connective tissue between the collagen fibers and the elastic fibers and between the cells and the connective tissue. Collagen fibers are produced in fibroblasts, and their important functions are mechanical rigidity of the skin, resistance of connective tissues, adhesion of tissues, and support of cell adhesion. Such collagen is reduced in its amount and deteriorated in its structure as it ages, and it has been pointed out as a main cause of endogenous skin aging and wrinkles. In addition, collagen fiber damage caused by ultraviolet rays can be considered as a cause of exogenous skin aging and wrinkles. Elastic fibers are important materials to maintain the elasticity of the skin. When it is denatured due to various causes, the skin elasticity is reduced. Substrate is a substance filling the dendritic connective fibers and cells, and is present in the form of gel without morphology. Glycosaminoglycan, which is a hydrophilic polysaccharide that forms a substrate, is also called a mucopolysaccharide because it exists in the form of a mucus dissolved in water.

Glycosaminoglycan (GAG) is a structure in which disaccharide-type sugars are repeatedly connected to each other to form hyaluronic acid, chondroitin sulfate, heparan sulfate, heparin, keratan sulfate sulfate, and dermatan sulfate. GAG can be roughly classified into two groups: Hyaluronic acid, which is a GAG containing no sulfate groups, and the remaining five groups including sulfate groups.

GAG is a major component of extracellular marix (ECM) in the skin and plays a role in filling void spaces between collagen fibers and elastic fibers, which are a large part of ECM, and recognizes changes in surrounding proteins or cells, Lt; / RTI > This affects the growth and differentiation of cells and their normal function. In addition, GAG has an excellent binding ability with water molecules and plays an important role in maintaining moisture of the skin. As the skin aging progresses due to internal or external causes, the amount of GAG present in the dermis decreases and the ability to newly synthesize GAG decreases. This increases the void space of the dermis to reduce wrinkles, reduce skin elasticity, The results are retrieved.

The wrinkle preventing and improving cosmetic materials that are used to improve the aging and wrinkles of the skin are products containing vitamin A (retinol) or retinyl palmitate. However, the products containing these raw materials are not only susceptible to changes over time, but also have a limited amount of use due to problems of stability such as skin irritation and redness when penetrated or decomposed into the skin at an effective concentration or more, The effect and moisturizing effect are insignificant.

It is also a common desire of many people in the modern world to have white skin. The color or brightness of the skin is genetically determined by the concentration and distribution of melanin in the human skin but is also influenced by environmental or physiological conditions such as sunlight, fatigue or stress. Melanin is produced by a nonenzymatic oxidation reaction of tyrosine, which is a kind of amino acid, with tyrosinase as a catalyst, followed by DOPA and Dopaquinone. The pathway for the formation of melanin is known, but the mechanism by which the melanin synthesis induces tyrosinase is not yet elucidated.

On the other hand, commonly known whitening ingredients include substances inhibiting the activity of tyrosinase enzymes such as kojic acid or albutin, hydroquinone, vitamin C (L-ascorbic acid) There are plant extracts. By inhibiting the synthesis of the melanin pigment, they can lighten the skin tone to realize whitening of the skin, and it is possible to improve skin hypercholesterolemia due to ultraviolet rays, hormones or heredity such as spots or freckles. However, when applied to skin, there is a problem that the use amount is limited due to safety problems such as irritation and redness, or the effect is insignificant, so that a practical effect can not be expected.

Therefore, it is urgently required to develop a wrinkle and elasticity improving and whitening active ingredient which is more safe than the living body, has a stable effective ingredient, and is more effective than the existing wrinkle and elasticity improvement and whitening effect.

In order to solve such a problem, the inventors of the present invention have found that, in order to prevent aging of the skin and to prevent aging of the skin, The present inventors have conducted continuous researches on ingredients for skin improvement that can suppress the occurrence of wrinkles and found that salvianolic acid A is excellent in promoting the synthesis of sulfated glycosaminoglycans and collagen type I of skin cells, -2, HAS-3 and melanin synthesis. Thus, the present invention has been accomplished by confirming that the present invention has excellent wrinkles, improved elasticity, moisturizing effect and whitening enhancing effect when applied to human body.

Accordingly, the present invention provides a method for promoting the synthesis of sulfated glycosaminoglycans of skin cells, promoting the synthesis of collagen type I, enhancing the expression of HAS-2, HAS-3, decreasing the total amount of melanin using salvianolic acid A A cosmetic composition, a pharmaceutical composition and a food composition having skin improving effect such as improvement or prevention of skin wrinkles, skin elasticity or aging of skin, moisturizing enhancement and whitening which can be applied to various formulations including salvianolic acid The purpose is to provide.

In order to accomplish the above object, the present invention provides a cosmetic composition comprising salvianolic acid A or a derivative thereof as an active ingredient.

The composition may be for promoting the synthesis of any one of sulfated Glycosaminoglycan, collagen and combinations thereof.

The composition may be for inhibiting melanin pigment.

The composition may be for aging the skin, wrinkling the skin, lowering the elasticity of the skin, lowering the moisture content of the skin, or improving or preventing aging.

The composition may be for skin whitening.

The content of salvianolic acid A contained in the composition may be 1 x 10 < ^-5 > to 10 wt% of the total composition.

The cosmetic composition may be in the form of a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleansing oil, a foundation, a cosmetic liquid, a cosmetic ointment, , A make-up remover, and a detergent.

In addition, the present invention provides a cosmetic comprising salvianolic acid A or a derivative thereof as an active ingredient.

The present invention also provides a pharmaceutical composition for the prevention or treatment of skin damage diseases comprising Salvianolic acid A or a derivative thereof as an active ingredient.

The skin damage disease may be selected from the group consisting of erythema, aging of the skin, wrinkles of the skin, decrease of the elasticity of the skin and decrease of the skin moisture content.

The present invention also provides a pharmaceutical composition for preventing or treating pigmentation diseases comprising salvianolic acid A or a derivative thereof as an active ingredient.

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.

The pharmaceutical composition may have a formulation selected from the group consisting of ointments, creams, tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, aqueous solutions, nonaqueous solutions, suspensions and emulsions .

The present invention also provides a health functional food composition comprising salvianolic acid A or a derivative thereof as an active ingredient.

The health functional food composition may be for aging the skin, wrinkling the skin, reducing the elasticity of the skin, reducing the moisture content of the skin, or improving or preventing aging.

The health functional food composition may be used for skin whitening.

In the case of a composition containing salvianolic acid A as an active ingredient, the present invention has the effect of improving or preventing skin aging, wrinkles, lowering of elasticity, lowering of moisture content, and whitening effect. Specifically, it promotes the biosynthesis of collagen (Type I) and sulfated glycosaminoglycan in the skin, thereby improving the mechanical rigidity of the skin and fundamentally improving and preventing deterioration of wrinkles, aging, and elasticity of the skin. It has an effect of inhibiting melanin synthesis and is excellent in whitening effect, so that it can be very usefully used in cosmetics, pharmaceuticals and food compositions. Also, as a natural material-derived substance, it can be usefully used for a long term without any side effects.

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

The salvianolic acid A may be represented by the following formula (1).

[Chemical Formula 1]

The compound of formula (1) is called salvianolic acid A and has a polyphenolic structure as a water-soluble compound, and is known as one of effective components of plant extracts.

The salvianolic acid A can be chemically synthesized through various organic chemistry methods known in the art and can be easily obtained from plants and the like. Salvianolic acid A used in the present invention was purchased from Sigma-Aldrich (USA).

The derivative of salvianolinic acid A is meant to indicate that the effect of salvianolic acid A of the present invention is similar to that of salvianolic acid A of the present invention among compounds in which a partial structure of salvianolic acid A is substituted or changed.

The salvianolinic acid A inhibits, treats and improves wrinkles caused by wrinkles associated with collagen reduction and elasticity degradation, degradation of synthetic sulfosalicosaminoglycans and promotion of degradation, which are other constituents of dermal extracellular matrix And can be used as an effective ingredient for wound healing due to excellent healing efficacy of wounds generated in skin and the like, and can be used as an effective ingredient for treatment and improvement of whitening through inhibition of melanin production. In addition, since salvianolic acid A is retained in excellent efficacy even when contained in a small amount, it can be used as an effective ingredient for improving or preventing skin wrinkles, reduced skin elasticity or aging of skin or treating or improving whitening in pharmaceuticals or cosmetics There is a wide range of applications that can be used.

The salvianolic acid A promotes the biosynthesis of glycosaminoglycan sulfate and collagen type I and shows that collagen type I and the dermal extracellular matrix composition of the skin are maintained tightly.

In order to examine the effect of salvianolic acid A on human fibroblasts and keratinocytes in a specific example, it was found that when salvianolic acid A was administered to fibroblasts derived from human body, the concentration of glycosaminoglycan And increased production of collagen type I, thereby confirming the effect of keeping the composition of extracellular matrix compact (Table 1 and Table 2).

In a specific example, in order to investigate the effect of salvianolic acid A on enhancing the HAS-2 and HAS-3 expression of salvianolic acid A, salvianolic acid A was treated with hu- HAS-3 expression was increased (Table 3).

In addition, in a specific example, it was confirmed that when melanoma cells of rat melanoma cells were treated with salvianolic acid A to inhibit the melanin production of salvianolic acid A, melanin formation inhibition rate was 25% or more of that of the control ( Table 4).

In addition, it has been confirmed that salvianolic acid A is formulated into an external ointment or an essence formulation and exhibits excellent skin wrinkle improving effect when it is applied to human skin. Particularly, it has been confirmed that salvianolic acid A in the present invention exhibits excellent wrinkle-reducing effect even at a low concentration level, that is, when it is applied in a small amount.

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

Further, the cosmetic composition of the present invention may be for suppressing melanin pigment, preferably for suppressing melanin pigment synthesis.

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

The cosmetic composition comprising salvianolic acid A can increase the production of glycosaminoglycans sulfated in the skin, promote the generation of type 1 collagen and enhance the expression of HAS, thereby improving the skin, May be for improving or preventing skin aging, wrinkles of the skin, lowering of skin elasticity or lowering of skin moisture content.

In addition, the cosmetic composition containing salvianolic acid A has an effect of reducing the total amount of melanin pigment in the skin to exhibit a whitening effect, and thus may be a cosmetic composition for whitening.

It was experimentally confirmed that when the composition of the present invention was used, the skin moisture content and moisture retention capacity were increased (Table 4), and it was experimentally confirmed that skin elasticity improvement and anti-aging skin wrinkle prevention or improvement effect were excellent 5).

The term " skin aging " refers to a phenomenon of skin elasticity reduction, gloss reduction, wrinkle formation, weakening of regenerative power, or severe drying, which may be caused by time or external environment, Reduced extracellular matrix components, such as glycosaminoglycans, can be caused by a reduction in skin elasticity or wrinkles.

The term " skin wrinkles " of the present invention refers to the skin of the skin, which may be caused by a gene, a decrease in collagen present in the skin dermis, an external environment, etc., and an elastin and collagen, Skin wrinkles are produced when glycosaminoglycan sulfated to help.

The term " skin elasticity " is expressed by elastic fibers composed of elastin existing in the dermal layer. Such elastic fibers have a very low elastic modulus such as rubber, and are easily deformed by a small force. When removed, it easily returns to the original shape. The reduction of the sulfated glycosaminoglycan reduces collagen and elastin as well as makes it difficult to maintain the structure, resulting in reduced skin elasticity.

The term " moisturizing " means maintaining the homeostasis of the living body by appropriately adjusting water loss (moisture evaporation) and the like, and when the glycosaminoglycan sulfate sulfated together with hyaluronic acid in the skin is reduced, water loss may occur.

The term " whitening " refers to not only brightening the skin tone by inhibiting the synthesis of melanin pigment but also improving skin hyperpigmentation such as freckles caused by ultraviolet hormone or gene.

The term " prevention " refers to inhibiting or retarding skin aging or wrinkle formation, elasticity, or moisture content reduction, regardless of the cause of aging using the composition of the present invention, Refers to inhibiting or delaying the action of glycosaminoglycans sulfated and collagen type I in keratinocytes through the action of promoting biosynthesis of collagen type I.

The term " improvement " means any action that improves or alleviates the skin condition by maintaining or strengthening the ability of the skin to develop wrinkles, aging, and elasticity. Specifically, It means not only the reduction of elastin and collagen, but also the maintenance of their structure to improve the wrinkles, aging, elasticity or moisture content of the skin.

The amount of salvianolic acid A contained in the composition may be included in an effective amount.

The term " effective amount " refers to the amount of salvianolic acid A that can inhibit or delay the development of skin aging or wrinkles, alleviate already formed wrinkles, or inhibit melanocytes, Means

The effective amount of the salvianolic acid A contained in the composition of the present invention may vary depending on the form of commercialization of the composition, the method of applying the salvianolic acid A to the skin, and the time of staying on the skin. For example, when the composition is commercialized as a medicament for dermatological treatment, Salvianolic acid A may be contained at a higher concentration than in the case where it is commercialized as a cosmetic product that is applied to skin on a daily basis. In the case of a wash-off type cosmetic such as a make-up remover, a detergent and the like in which the active ingredient remains on the skin in a short period of time even when the product is made into a cosmetic product, it may contain a relatively high concentration of salvianolic acid A. On the other hand, leave-on type cosmetics such as lotion, cream, essence, etc., which remain in the skin for a long period of time, contain lower concentrations of salvianolic acid A than those of wash- It may be possible.

The content of salvianolic acid A contained in the composition may be 1 × 10 ^-5 to 10% by weight, and preferably 0.0001 to 1% by weight of the total composition. It is difficult to obtain the effect of promoting the production of collagen type I and the synthesis of sulfated glycosaminoglycan in skin cells at a concentration of less than 0.00001% by weight of the composition, and at a concentration of more than 10% by weight of the composition, The overall processability is deteriorated, and there is a possibility that use for various purposes such as cosmetic formulations to be described later is limited.

The preferable concentration of salvianolic acid A contained in the composition is 0.1 μg / ml to 100 μg / ml, more preferably 1 μg / ml to 50 μg / ml, still more preferably 5 μg / ml to 25 μg / Mu] g / ml.

The composition may be used in any formulation that can be applied to the envelope. Specific examples include solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansers, oils, foundations, lotions, cosmetic creams, sprays, packs, sunscreens, makeup bases, Removing agents and detergents, and is not limited to the above examples.

In addition, the composition can be used as an external preparation for skin for improving skin elasticity, preventing skin aging, improving skin wrinkles and whitening.

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

The cosmetic composition containing salvianolic acid A according to the present invention can be used as a cosmetically acceptable carrier, diluent, adjuvant, coloring agent, stabilizer, flavoring agent, surfactant, oil, moisturizer, alcohol, An antioxidant, a pH adjusting agent and a sunscreen agent. When the composition is used as a composition for external use on the skin, it can be applied to a skin such as a liquid, oil, cream, ointment, stick, pack, pasta, Any formulation can be used.

The cosmetic composition may further comprise a cosmetically acceptable excipient to facilitate its use and handling. The cosmetically acceptable excipient includes a surfactant, an emulsifier, a soap acid, a solvent, a binder, a diluent, a lubricant, a stabilizer, a perfume, water, a lower alcohol, a thickener, a chelating agent, a pigment, a preservative, a colorant, Antioxidants, antifoaming agents, antimicrobial agents, antifouling agents, enzymes, plant or mineral oils, fats, fluorescent substances, fungicides, flocculants, humectants, fragrances, fragrance carriers, preservatives, proteins, silicones, Blockers, vitamins, plant extracts or waxes. These may be used alone or in combination of two or more.

When the cosmetic composition is formulated into cosmetics, it may contain known dermatologically acceptable excipients that act as a carrier for the active ingredient. Specifically, the cosmetic composition may include International cosmetic ingredient dictionary, 6th ed., The cosmetic, Toiletry and Fragrance Association , Inc., Washington, 1995, which is incorporated herein by reference in its entirety. Which are incorporated herein by reference.

The present invention also relates to a cosmetic comprising salvianolic acid A or a derivative thereof as an active ingredient.

The cosmetic may be any one selected from the group consisting of lotion, essence, skin, lotion, cream, and pack.

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, Cleansing lotion, cleansing cream, body lotion and body cleanser, but is not limited thereto.

The present invention also relates to a pharmaceutical composition for preventing or treating a skin damaging disease comprising salvianolic acid A or a derivative thereof as an active ingredient.

The present invention also relates to a pharmaceutical composition for preventing or treating a pigment deposition disease comprising salvianolic acid A or a derivative thereof as an active ingredient.

The present invention also relates to pharmaceuticals or quasi-drugs containing the above pharmaceutical composition.

The pharmaceutical composition refers to a medicament for the purpose of diagnosing, treating, alleviating, treating or preventing an illness in an animal including a human being.

The skin damage disease refers to a disease caused by skin damage, and may be selected from the group consisting of erythema, skin aging, skin wrinkles, skin elasticity reduction, skin moisture content reduction, and aging .

The pigmentation disorder refers to any disease associated with the symptom of excessive proliferation or deposition of the pigment, and preferably includes freckles, senile spots, liver, spots, brown or black spots, daylight pigment spots, cynic melisma, , Hyperpigmentation after drug use, gravidic chloasma, and hyperpigmentation after inflammation due to wound or dermatitis.

The pharmaceutical composition may contain 0.001 wt% to 99.9 wt% or 0.1 wt% to 99 wt% or 1 wt% to 20 wt% of the extract, based on the total weight of the composition, but is not limited thereto, Depending on the method of use, the content of the extract may be suitably adjusted to a pharmaceutically effective amount or a desired amount.

The preferred dosage of the pharmaceutical composition of the present invention varies depending on the age, sex, weight, symptom, degree of disease, drug form, administration route and period of time of the subject, but can be appropriately selected by those skilled in the art. For the desired effect, the pharmaceutical composition of the present invention is preferably administered at 0.01 to 1000 mg / day. The administration can be done once a day, or divided into several times. In addition, the dose may be increased or decreased according to age, sex, weight, degree of disease, route of administration, and the like. Accordingly, the dose does not limit the scope of the present invention in any aspect.

The composition can be administered to mammals such as rats, mice, livestock, humans, and the like in a variety of routes including parenteral, oral, and the like, all manner of administration being expected, for example oral, rectal or intravenous, , Subcutaneous, intrauterine or intracerebroventricular injection.

The pharmaceutical composition of the present invention may contain the salvianolic acid A as an active ingredient alone and may further contain a pharmaceutically acceptable carrier, excipient, diluent, and / or sub ingredient depending on the formulation, .

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.

These components may be added to the active ingredient salvianolic acid A independently or in combination.

The formulations of the pharmaceutical compositions may vary depending on the method of use and may be formulated using methods well known in the art to which the present invention pertains so as to provide rapid, sustained or delayed release of the active ingredient after administration to the mammal . Examples of the formulations may be formulations selected from the group consisting of ointments, creams, tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, aqueous solutions, nonaqueous solutions, suspensions and emulsions .

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.

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.

In the present invention, when the pharmaceutical composition is formulated into pharmaceuticals, reference is made to Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA, which is incorporated herein by reference.

In addition, the pharmaceutical composition of the present invention can be used alone for improving, alleviating, treating or preventing skin, 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.

The present invention also relates to a health functional food composition comprising salvianolic acid A or a derivative thereof as an active ingredient.

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

In addition, the composition may be a health functional food composition for skin whitening.

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 other components other than the salvianolic acid A of the present invention as an essential ingredient in the indicated ratios and may contain various flavors or natural carbohydrates as an additional ingredient .

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 additive is not so critical, but may be selected in the range of 0 to 20 parts by weight per 100 parts by weight of the salvianolic acid A 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 needed, and is preferably 0.00001 to 10 wt% As shown in Fig.

The present invention also relates to the use of salvianolic acid A for the preparation of said cosmetic, pharmaceutical or food composition and to a method for improving skin comprising applying or taking an effective amount of salvianolic acid A on the skin.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the examples.

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

Salvianolic acid A was added to the culture medium of human fibroblast to confirm the promoting effect of collagen synthesis at the cellular level. The salvianolic acid A used was purchased from Sigma Aldrich (USA). The synthesized collagen was quantitated using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immuno Assay Kit).

The final concentration of salvianolic acid A in the experiment was 10 ㎍ / ml and 20 ㎍ / ml. Salvianolic acid A was added to culture medium (DMEM medium) of human-derived fibroblasts and cultured for 48 hours. The culture broth was taken and the degree of collagen synthesis was measured at 450 nm using a PICP EIA kit using a spectrophotometer at each concentration .

For the comparison of the effects, the degree of collagen synthesis was measured in the same manner in the culture medium of the fibroblasts to which nothing was added (control group) and the sample to which TGF-beta was added so as to have a final concentration of 10 ng / ml.

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

sample Collagen production (ng / ml)) Growth rate (%) Control group 178 - TGF-beta 10 ng / ml 470 164 Salvianolic acid A 10 μg / ml 334 88 Salvianolic acid A 20 μg / ml 430 142                                                  (Number of repetitions = 4)

As shown in Table 1 above, salvianolic acid A showed lower collagen production at almost all concentrations than that of TGF-beta, which is generally known to have collagen synthesis ability, And the collagen synthesis effect was increased.

[ Example  2] in human fibroblasts Sulfation Of glycosaminoglycan  Confirmation of synthesis promotion effect

Salvianolic acid A was added to the culture medium of human fibroblast to confirm the effect of promoting the synthesis of sulfated glycosaminoglycan at the cellular level. Measurement of glycosaminoglycan sulfate was quantitated using Blyscan glycosaminoglycan assay kit (Biocolor).

The final concentration of salvianolic acid A in the experiment was 1 ㎍ / ml, 10 ㎍ / ml, and 20 ㎍ / ml. Salvianolic acid A was added to the culture medium of human fibroblast (DMEM medium) for 24 hours, and then the culture broth was taken and analyzed with a Blyscan glycosaminoglycan assay kit to determine the concentration of total sulfated glycosaminoglycan The amount was measured at 656 nm using a spectrophotometer.

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

Samples (/ / ml) Production amount of glycosaminoglycan sulfate (ng / ml) Growth rate (%) Control group 0.46 -  Salvianolonic acid A 1 ug / ml 0.57 24 Salvianolic acid A 10 μg / ml 1.59 247 Salvianolic acid A 20 μg / ml 3.29 615                                                 (Number of repetitions = 4)

As shown in the above Table 2, in the treatment groups treated with 10 μg / ml and 20 μg / ml salvianolic acid A, respectively, as compared with the control group not treated with salvianolic acid A, the excellent sulfated glycosaminoglycan It was confirmed that there was an effect of promoting glycan synthesis.

[ Example  3] In keratinocytes derived from human body Salvianolic acid  Increased expression of hyaluronan synthase (HAS) gene by A

The culture solution containing 1 ppm and 10 ppm of salvianolic acid A was treated for 24 hours with human keratinocytes. Cells were recovered and total RNA was extracted with RNeasy mini kit (Qiagen), and 1 μg of RNA was quantified and reverse transcribed using GeneAmp ^® RNA PCR kit (Applied Biosystems). The reverse transcription reaction was performed using a Mycycler ^® PCR instrument (Biorad).

Quantitative real time PCR was performed using 2 μl of the 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 by real time PCR were calculated by the method described in Livak KJ et al. (Methods, 2001, 25, 402-408) on the basis of the housekeeping gene GAPDH.

In addition, experiments were conducted as described above with respect to 100 ppm of glucosamine, and mRNA expression levels of glucosamine 100ppm (glucosamine) and salvianolic acid A treatment group were quantified by using the amount of mRNA expression of the negative control as a reference (100%) Table 3 shows the results.

sample No treatment
(Negative control) Glucosamine
100 ppm Salvianolic acid A
1 ppm Salvianolic acid A
10 ppm HAS-2
Expression level (%) 100 114 120 138 HAS-3
Expression level (%) 100 125 131 147 (Number of repetitions = 4)

As shown in Table 3 above, the expression of hyaluronic acid synthase, especially HAS-2 and HAS-3, was increased in human keratinocytes by salvianolinic acid A treatment. In addition, Salvianolic acid A showed an increase in the expression of HAS-2 and HAS-3, which is 100 times smaller than that of the positive control, Glucosamine, compared with the positive control. As a result, salvianolic acid A It has been confirmed that it has a good moisturizing effect even in a small amount and has a moisturizing effect against a decrease in moisture retention even in a small amount.

[ Example  4] Melanoma  Cells (B-16 mouse melanoma cell) Salvian Nol Inhibitory Effect of Ricin A on Melanogenesis

Salvianolic acid A was added to the culture medium of rat B-16 mouse melanoma cells to examine the whitening effect at the cellular level (Lotan R., Lotan D. Cancer Res. 40: 3345-3350, 1980). To evaluate the toxicity of melanoma cells in rats before the experiment, whitening evaluation was performed by selecting a concentration that is not toxic.

B-16 melanoma cells were treated with the compound of formula (1) in a final concentration of 1 μg / ml and 10 μg / ml in a culture medium, and the control group albutin was added to the medium to a concentration of 200 μg / Lt; / RTI >

Cells were then trypsinized, detached from the culture, centrifuged, and extracted with melanin. The removed cells were incubated with 1 ml of sodium hydroxide solution (1N), boiled for 10 minutes to dissolve melanin, and the absorbance was measured at 400 nm using a spectrophotometer to determine the amount of melanin produced. The amount of melanin was measured by an absorbance of 10 ⁶ cells per unit cell number, and the amount of melanin produced relative to the control group was calculated as an inhibition rate (%). The results are summarized in Table 4 below.

Sample group Negative control group Positive control group
Arbutin 200 μg / ml Salvianolic acid A
10 μg / ml Salvianolic acid A
1 / / ml Inhibition rate - 31.3% 38.1% 29.1% (Number of repetitions = 3)

As shown in Table 4, melanin formation inhibitory effect at the cell level according to the concentration was confirmed, and as a result, salvianolic acid A was found to inhibit melanin production in melanoma cells at 1/20 level of positive control, (Arbutin) and showed almost similar melanin formation inhibitory activity at 1/200 level. Therefore, it can be seen that salvianolic acid A has a remarkably superior whitening activity effect even at a lower concentration than conventional materials.

[Preparation Example 1 and Comparative Example 1] Preparation of external ointment for skin

Skin external ointment containing salvianolic acid A as an active ingredient was prepared according to a conventional method as shown in the composition of Table 5 below. In addition, the ointment for external use for skin prepared from the other ingredients except for the active ingredient was prepared in Comparative Example 1.

Composition (% by weight) Production Example 1 (% by weight) Comparative Example 1 (% by weight) Salvianolic acid A 0.2 0 Diethyl sebacate 8 8 Nonsense 5 5 Polyoxyethylene oleyl ether phosphate 6 6 Sodium benzoate One One vaseline to 100 to 100

[Preparation Example 2 and Comparative Example 2] Preparation of essence

Comparative Example 2 was prepared in the same manner as in Preparation Example 2 except that the formulation of cosmetic essence containing salvianolinic acid A as an active ingredient was prepared in Preparation Example 2 and cosmetic essence was prepared in the same manner as in Preparation Example 2, The detailed composition is shown in Table 6 below.

Composition (% by weight) Production Example 2 (% by weight) Comparative Example 2 (% by weight) Salvianolic acid A 0.5 0 glycerin 10.0 10.0 Sodium hyaluronate aqueous solution (1%) 5.0 5.0 Polyoxyethylene hardened 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 skin wrinkle-reducing effect was tested as follows for healthy 35- to 50-year-old women.

30 women aged 35 to 50 years were divided into two groups of 15 persons. Group 1 contained the essence of Preparation Example 2 containing 0.5% salvianolic acid A, Group 2 contained the essence of Comparative Example 2 in the face area Once a day for 3 months. After 3 months, the improvement of skin wrinkles was evaluated by questionnaires. The subjects' questionnaires were judged to have no improvement, little improvement, and considerable improvement as compared with before use in terms of improvement in skin wrinkles and elasticity, and the results are shown in Table 7 below.

Category (persons) No improvement Slight improvement A significant improvement Production Example 2 2 5 8 Comparative Example 2 7 5 3

As shown in Table 7, when the essence of Preparation Example 2 containing 0.5% salvianolic acid A was used, it was confirmed that the effect of improving skin wrinkles was superior to that of the essence of Comparative Example 2, which was not used.

[Experimental Example 2] Wrinkle-improving effect test of cosmetic essence through image analysis

The wrinkle-improving effect was evaluated for the essences of Preparation Example 2 and Comparative Example 2 through image analysis.

Specifically, the replica under the eye was sampled (Xantopren, Bayer) before the experiment was started, and the replica was sampled from the same site under the eye immediately after the experiment was completed. The density of skin wrinkles was measured by analysis. The reduction rate of the skin wrinkle density by image analysis is a value obtained by averaging the ratio of the skin wrinkle density after use to the skin wrinkle density before use of the essence, and the measurement results are shown in Table 8 below.

Skin Wrinkle Density Reduction (%) Comparative Example 2 32 Production Example 2 59

As shown in Table 8, when the essence of Preparation Example 2 containing salvianolic acid A was used, it was found that the effect of improving skin wrinkles was superior to that of the essence of Comparative Example 2 containing no salvianolic acid A . No skin irritation or side effects due to the essence of Preparation Example 2 were found in the above test procedure.

Claims (16)

A cosmetic composition comprising salvianolic acid A or a derivative thereof as an active ingredient. The method according to claim 1,
Wherein the composition is for promoting the synthesis of any one of sulfated glycosaminoglycan, collagen, and combinations thereof. The method according to claim 1,
Wherein the composition is for inhibiting melanin pigment. The method according to claim 1,
Wherein the composition is adapted for improving or preventing skin aging, wrinkles, skin elasticity or skin moisture content. The method according to claim 1,
Wherein the composition is for skin whitening. The method according to claim 1,
Wherein the content of salvianolic acid A in the composition is 1 x 10 < ^-5 > to 10 wt% of the total composition. 7. The method according to any one of claims 1 to 6,
The cosmetic composition may be in the form of a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleansing oil, a foundation, a cosmetic liquid, a cosmetic ointment, , A makeup removing agent, and a detergent. A cosmetic comprising salvianolic acid A or a derivative thereof as an active ingredient. A pharmaceutical composition for preventing or treating skin damage diseases comprising salvianolic acid A or a derivative thereof as an active ingredient. 10. The method of claim 9,
Wherein the skin damage disease is selected from the group consisting of erythema, aging of the skin, wrinkles of the skin, lowering of the elasticity of the skin and lowering of the skin moisture. A pharmaceutical composition for the prevention or treatment of pigmentation diseases comprising salvianolic acid A or a derivative thereof 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. The method according to any one of claims 9 to 12,
The pharmaceutical composition is a pharmaceutical composition having a formulation selected from the group consisting of ointments, creams, tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, aqueous solutions, non-aqueous solutions, suspensions and emulsions . A health functional food composition comprising salvianolic acid A or a derivative thereof as an active ingredient. 15. The method of claim 14,
The health functional food composition is for improving or preventing aging of the skin, wrinkles of the skin, lowering of skin elasticity, lowering of the moisture content of the skin or aging. 15. The method of claim 14,
Wherein said health functional food composition is skin whitening.