Use of compounds for the preparation of a composition for whitening the skin and a method for skin whitening using the same

Abstract

Provided are a use of a compound represented by the following Chemical Formula 1 for preparing a composition for whitening skin and a method of whitening skin of an individual, comprising the step of administering the compound to the individual, in which: 【Chemical Formula 1】in the Chemical Formula 1, each substituent is defined in the description.

Description

TECHNICAL FIELD

[0001] The present description relates to the use of a compound for preparing a composition for whitening skin and a method for whitening skin using the same. BACKGROUND

[0002] Skin plays a variety of essential functions in the life of a human being. A barrier function for maintaining homeostasis of the human body to correspond to environmental changes, a sensory function for sensing external changes, a body temperature regulating function, etc. are the most representative functions of skin. Among the various functions of skin, the barrier function of skin is mainly embodied by the stratum corneum, which is the outermost layer of the skin. It has been reported that the stratum corneum not only simply plays a barrier function, but also affects the function and role, structure, etc. of the cell layer, i.e. the epidermis or dermis, present in the inside, and thus its importance is continuously increasing. The stratum corneum is composed of necrotic keratinocytes and intercellular lipids, and is responsible for the core function as a skin protective film that protects the skin from external stimuli and prevents evaporation of moisture from the inside. In addition, the keratinocytes of the stratum corneum form a skin barrier through a differentiation and keratinization process.

[0003] The epidermis including the stratum corneum can be divided into the stratum corneum, the stratum lucidum, the stratum granulosum, the stratum spinosum, and the stratum basale. Melanin is present on the stratum basale, which is the lowermost layer of the epidermis. Melanin refers to a brown pigment contained in tissues such as skin and eyes, and is generated by melanocytes.

[0004] Melanin expression genes vary from person to person, thereby adjusting the amount of melanin and determining skin color. That is, the more the amount of melanin, the darker the skin color, etc. Specifically, the amount of melanin is determined by the number, concentration, melanin secretion ability, etc. of melanosomes in melanocytes, and the skin color is determined by the factors.

[0005] Melanin has a function of blocking a certain amount or more of ultraviolet rays, thereby maintaining the body temperature of the skin and protecting the skin from ultraviolet rays. Melanin can also block ultraviolet rays that penetrate the skin, but when the skin is exposed to ultraviolet rays for a long time, melanocytes are stimulated to increase the amount of melanin generated. When the melanin thus generated moves to the stratum corneum of the skin and accumulates on the stratum corneum, a pigmentation phenomenon occurs. As the pigmentation phenomenon that occurs on the skin, there are chloasma, freckles, spots, etc.

[0006] Melanin is a high molecule formed through an oxidation process of tyrosine protein by tyrosinase. Therefore, the generation of melanin can be prevented by inhibiting the activity of tyrosinase or by inhibiting the oxidation of tyrosine. In addition, the pigmentation can be prevented by not allowing the generated melanin to accumulate on the stratum corneum. Inhibiting pigmentation is directly related to lightening skin color, thereby whitening skin, and in this regard, the interest in preventing and improving pigmentation is increasing, and many efforts have been made to develop a whitening functional product.

[0007]

PRIOR ART DOCUMENTS

[0008] (Patent Document 0001) Japanese Laid-Open Patent No. 2008-534619 (Published on August 28, 2008) SUMMARY

[0009] TECHNICAL PROBLEM

[0010] One implementation example intends to provide a use of a compound for preparing a whitening composition, which can impart an excellent whitening effect to skin by inhibiting the generation of melanin through the inhibition of expression of a protein that is a melanin generation enzyme.

[0011] Another implementation example intends to provide a method of whitening skin of an individual, which includes the step of administering the cosmetic composition to the individual.

[0012] TECHNICAL SOLUTION

[0013] According to one implementation example, there is provided a use of a compound represented by the following Chemical Formula 1 for preparing a whitening composition.

[0014] [Chemical Formula 1]

[0015]

[0016] In the Chemical Formula 1,

[0017] R1 to R4 are each independently a hydrogen atom or a substituted or unsubstituted C1 to C10 alkyl group, X is a hydrogen atom, a hydroxyl group, or a carboxyl group, and at least one of R1 to R3 is a methyl group.

[0018] It can be that R1 to R3 are each independently a methyl group, R4 is an iso-pentyl group, and X is a hydroxyl group.

[0019] The compound represented by the Chemical Formula 1 can be contained at a concentration of 0.1 µM to 1 mM with respect to the total amount of the whitening composition.

[0020] The compound represented by the Chemical Formula 1 can be contained at a concentration of 1 µM to 50 µM with respect to the total amount of the whitening composition.

[0021] The whitening composition can be a cosmetic composition or a food composition.

[0022] According to another embodiment, there is provided a method for whitening the skin of an individual, the method including the step of administering to the individual a cosmetic composition containing, as an active ingredient, a compound represented by Chemical Formula 1.

[0023] According to still another embodiment, there is provided a use of a compound represented by Chemical Formula 1 for the preparation of a whitening composition.

[0024] According to still another embodiment, there is provided a method for whitening the skin of an individual, the method including the step of applying to the skin a composition containing a compound represented by Chemical Formula 1.

[0025] The compound represented by Chemical Formula 1 and the concentration thereof can be as described above.

[0026] Effects of the Invention

[0027] The composition according to an embodiment can inhibit the production of melanin by inhibiting the expression of a protein that is a melanin-producing enzyme, thereby being able to impart an excellent whitening effect to the skin to which the composition is applied. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 is a graph showing the amount of melanin production according to the concentration of a compound represented by Chemical Formula 1-1 and whether or not there is ultraviolet light;

[0029] Figure 2 is a photograph showing the suspension of melanin-producing cells according to the concentration of a compound represented by Chemical Formula 1-1;

[0030] Figure 3 is a graph showing the amount of melanin-producing cells according to the concentration of a compound represented by Chemical Formula 1-1 and whether or not there is ultraviolet light;

[0031] Figure 4 is a graph showing the expression amount of tyrosinase, which is a melanin-producing enzyme, according to the concentration of a compound represented by Chemical Formula 1-1 and whether or not there is ultraviolet light;

[0032] Figure 5 is a graph showing the relative ΔL value according to whether or not a compound represented by Chemical Formula 1-1 is contained and the concentration thereof. DETAILED DESCRIPTION

[0033] Hereinafter, embodiments of the present application will be described in detail so that those having ordinary knowledge in the technical field to which the present application pertains can easily practice the present application. However, the present application can be implemented in various different forms, and is not limited to the embodiments described herein.

[0034] In the present specification, the improvement of the skin whitening function means the lightening of the color of the stratum corneum, which is the outer layer of the skin. The stratum corneum, which is the first defense membrane of the skin, is easily damaged by the external environment. In order to impart the whitening ability to the skin, it is possible to temporarily solve the problem by applying a skin external agent as prescribed, but it is difficult to solve the problem fundamentally, and further, the skin external agent is not used to solve the problem, but has only the effect of simply hiding the degree of internal black marks of the skin, and thus it has not been possible to fundamentally improve the pigmentation problem of the skin by simply applying the prescription of the skin external agent so far. For this reason, the present inventors have confirmed that the compound represented by a specific chemical formula, which constitutes the composition according to one embodiment, can solve the problem fundamentally as described above, thereby fundamentally improving the skin whitening effect, and thus the present invention has been completed.

[0035] More specifically, the composition according to one embodiment can be expected to have a skin whitening effect by regulating the signal transduction with respect to the expression of the melanin-producing enzyme (tyrosinase) involved in the synthesis of melanin.

[0036] In this regard, it has been reported that the production of melanin is increased when the intracellular concentration of c-AMP is increased, and the production of melanin is decreased when the extracellular signal regulated kinase (ERK) signaling pathway is activated. However, as a method of activating the extracellular signal regulated kinase signaling pathway, a method of stimulating the signal transduction pathway that phosphorylates the extracellular signal regulated kinase is known, and recently, when protein phosphatase 2A (PP2A), which is an enzyme that dephosphorylates the extracellular signal regulated kinase, is inhibited, the extracellular signal regulated kinase is activated, and thus it is finally expected that the skin whitening effect is obtained through the decomposition of Microphthalmia-associated transcription factor (MIITF), but an effective method of inhibiting the protein phosphatase 2A has not been disclosed recently.

[0037] In this regard, the present inventors have confirmed that when a composition containing a specific compound in a specific concentration range as an active ingredient is treated to melanocytes, it has an effect of inhibiting the synthesis of melanin-producing enzyme (tyrosinase), and thus the present invention has been completed.

[0038] On the other hand, as the aforementioned method, a substance directly inhibiting a melanin production enzyme (tyrosinase) requires use of a high concentration, and thus not only can show side effects such as skin irritation, but also kojic acid is in a state of being prohibited from use due to the possibility of causing skin cancer. However, the composition according to an embodiment does not stimulate the skin and has almost no side effects while showing a very strong whitening effect by inhibiting the production of a melanin production enzyme (tyrosinase) since it is not a substance directly inhibiting a melanin production enzyme (tyrosinase).

[0039] In the present specification, when a layer, film, region, plate, or the like is referred to as being "on" another layer, film, region, plate, or the like, it can be "directly on" the other layer, film, region, plate, or the like, or an intervening layer, film, region, plate, or the like can also be present. Conversely, when a layer, film, region, plate, or the like is referred to as being "directly on" another layer, film, region, plate, or the like, intervening layers, films, regions, plates, or the like are not present.

[0040] In the present specification, "combination" means mixing or copolymerization unless otherwise defined. In addition, "copolymerization" means block copolymerization or random copolymerization, and "copolymer" means block copolymer or random copolymer.

[0041] Hereinafter, a skin-whitening composition according to an embodiment will be described.

[0042] Use of a compound represented by the following Chemical Formula 1 according to an embodiment for the preparation of a skin-whitening composition.

[0043]

Chemical Formula 1

[0044]

[0045] In the Chemical Formula 1,

[0046] R1 to R4 are each independently a hydrogen atom or a substituted or unsubstituted C1 to C10 alkyl group, X is a hydrogen atom, a hydroxyl group, or a carboxyl group, and at least one of R1 to R3 is a methyl group.

[0047] For example, in the Chemical Formula 1, R1 to R3 can each be independently a methyl group, R4 can be an isoamyl group, and X can be a hydroxyl group.

[0048] The compound represented by the Chemical Formula 1 can impart a whitening effect to the skin by hindering an increase in expression of tyrosinase, which is a melanin production enzyme.

[0049] Excessive pigmentation of the skin can be caused by various factors such as abnormal hormone levels in the body after an inflammatory reaction of the skin, genetic diseases, and ultraviolet radiation, and as a primary cause, abnormal melanin synthesis and abnormal distribution can be cited.

[0050] The main function of melanin is to remove oxygen radicals, thereby protecting the skin from damage caused by oxygen radicals. Therefore, melanin is generally considered to have an effective coping system for protecting the skin from physical and chemical toxic substances. As described above, the production of melanin is accomplished by the action of enzymes and spontaneous oxidation reactions after conversion of tyrosine to Dopaquinone in melanocytes by tyrosinase.

[0051] Methods for inhibiting melanin production known so far are as follows.

[0052] First, there is a method of blocking ultraviolet rays, thereby removing the main cause of melanin production. This method can be expected to have excellent effects by including a light scattering agent or a light blocking agent in the cosmetic composition.

[0053] Next, the production of melanin can be inhibited by hindering the synthesis of core carbohydrates, such as glucosamine, which are required in the activity of tyrosinase.

[0054] In addition, the function of tyrosinase, which is an enzyme involved in the production of kojic acid or arbutin, can be hindered.

[0055] Further, substances such as hydroquinone, which are specifically toxic to melanocytes that produce melanin, can be used to inhibit the division of melanocytes.

[0056] In addition, methods for decolorizing reduced melanin have also been introduced.

[0057] Most of the researches for finding a whitening composition have been focused on a substance that directly inhibits melanogenesis enzyme (tyrosinase) involved in melanin synthesis. However, in addition to directly inhibiting melanogenesis enzyme (tyrosinase), a technique that can expect a whitening effect by regulating signal transduction involved in the expression of melanogenesis enzyme (tyrosinase) has been suggested (Briganti S, Camera E, Picardo M. Pigment Cell Res, 2003, 16(2): 101-10).

[0058] In addition, it is known that melanogenesis enzyme (tyrosinase) is produced by the regulation of MITF (microphthalmia-associated transcription factor) as a transcription factor when it is affected by external stimuli or hormones, etc. (DS Kim, ES Whang, JE Lee, SY Kim, SB Kwon, and KC Park. J Cell Sci. 2003; 116: 1699-706), but a method for reducing the production of melanin by inhibiting the expression of the MITF has not been introduced.

[0059] The composition according to an embodiment reduces the production of melanin, and in particular, has an excellent effect of inhibiting the increase in protein expression of tyrosinase as a melanogenesis enzyme in melanocytes. Therefore, when used on skin where hyperpigmentation occurs, the skin whitening effect is very excellent. For example, when the composition according to an embodiment is applied to skin where pigmentation occurs, a very excellent skin whitening effect can be expected.

[0060] In the Chemical Formula 1, the configuration of the substituent or a part of hydrogen atoms attached to the parent is specified, and the skin whitening effect can be greatly improved by having the configuration as described above.

[0061] An embodiment provides a use of a compound represented by the Chemical Formula 1 for preparing a composition for whitening, and the compound represented by the Chemical Formula 1 can be contained alone in a pharmaceutically effective amount or include one or more pharmaceutically acceptable carriers, excipients, or diluents.

[0062] In the composition, the compound represented by Chemical Formula 1 can be contained at a concentration of 0.1 µM to 1 mM, for example, at a concentration of 1 µM to 50 µM, relative to the total amount of the skin-whitening composition. When the compound represented by Chemical Formula 1 is used at a concentration of less than 0.1 µM, the degree of inhibition of the phenomenon of increasing the protein expression of tyrosinase in melanocytes is weak, and thus the skin-whitening function-improving effect cannot be exhibited, and at a concentration of less than 1 µM, the degree of the skin-whitening function-improving effect can be weak.

[0063] In addition, when the compound represented by Chemical Formula 1 is used at a concentration exceeding 1 mM, there can be no large difference in the skin-whitening effect compared to the case where the compound represented by Chemical Formula 1 is contained at a concentration of 0.1 µM to 1 mM, but rather, the compound represented by Chemical Formula 1 is unnecessarily contained in excess, and thus the action of other functional ingredients in the composition and the like can be limited, and thus it can not be preferable.

[0064] The above "pharmaceutically effective amount" means an amount of the physiologically active ingredient to be administered to an animal or a human to exhibit a sufficient amount of the intended physiological or pharmacological activity. However, the pharmaceutically effective amount can be appropriately changed depending on the degree of symptoms, the age, body weight, health status, sex of the patient, the administration route, and the treatment time, and the like.

[0065] In addition, the above "pharmaceutically acceptable" means that it is physiologically allowable and does not generally cause allergic reactions such as gastrointestinal disorders, dizziness, and the like, or reactions similar thereto, when administered to humans. As examples of the carriers, excipients, and diluents, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginic acid, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil can be mentioned. In addition, a filler, an anticoagulant, a lubricant, a wetting agent, a flavor, an emulsifier, a preservative, and the like can also be contained.

[0066] For example, the composition can be a cosmetic composition.

[0067] In the present specification, "cosmetic" can mean all substances having not only a cosmetic function but also a medical function in addition to the cosmetic function.

[0068] The dosage form of the cosmetic composition is not particularly limited, and can be appropriately selected depending on the purpose.

[0069] For example, the cosmetic composition can be formulated into a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powder foundation, a cream foundation, a wax foundation, a spray, and the like, but is not limited thereto.

[0070] More specifically, the cosmetic composition can be formulated into a cleansing agent, a tonic, a hair styling agent, a nourishing lotion, an essence, an essence cream, a hair pack, a hair conditioner, a shampoo, a lotion, a hair treatment agent, or a hair dye, and the like; a base cosmetic of an oil-in-water (O / W) type, a water-in-oil (W / O) type, or the like. For example, the composition can have a dosage form selected from the group consisting of a moisturizing cream, a moisturizing lotion, a toner, a lotion, a milk lotion, a moisturizing cream, a nourishing cream, a massage cream, a nourishing cream, a moisturizing cream, a hand cream, an ointment, a foundation, an essence, a nourishing essence, a pack, a soap, a cleansing foam, a cleansing cream, a cleansing cream, a body lotion, a body wash, a lotion, an ointment, a gel, a cream, a patch, and a spray.

[0071] In addition, the composition can be formulated with other components in addition to the essential components, which can be appropriately selected and formulated by those skilled in the art according to the type or purpose of use of the other external agent. For example, an ultraviolet blocking agent, a hair care conditioner, a fragrance, or the like can be further included.

[0072] The cosmetic composition can contain a cosmetically acceptable medium or base. It can be provided in all dosage forms suitable for topical use, such as a solution, a gel, a solid or paste anhydrous product, an emulsion obtained by dispersing an oil phase in an aqueous phase, a suspension, a microemulsion, a microcapsule, a microspherule, or an ionic (liposome) and / or non-ionic vesicular dispersion agent, or a cream, a lotion, a lotion, a powder, an ointment, a spray, or a concealer stick. The composition can be prepared according to conventional methods in the art.

[0073] When the dosage form of the present application is a solution or an emulsion, as a carrier component, a solvent, a solubilizer, or a demulsifier is used, for example, a fatty acid ester of water, ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol oil, glycerol fatty ester, polyethylene glycol, or sorbitol.

[0074] When the dosage form of the present application is a suspension, as a carrier component, a liquid diluent such as water, ethanol, or propylene glycol; a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester; microcrystalline cellulose; aluminum metahydroxide; bentonite, agar, or tragacanth gum, and the like can be used.

[0075] When the dosage form of the present application is a paste, cream or gel, as a carrier component, animal oil, vegetable oil, wax, paraffin, starch, tragacanth gum, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicon oxide, talc or zinc oxide, etc. can be used.

[0076] When the dosage form of the present application is a powder or spray, as a carrier component, lactose, talc, silicon oxide, aluminum hydroxide, calcium silicate or polyamide powder, and especially for a spray, a propellant such as chlorofluorocarbon, propane / butane or dimethyl ether can be contained.

[0077] In an embodiment of the present application, the cosmetic composition can further contain a viscosity increasing agent. The viscosity increasing agent contained in the cosmetic composition of the present application can use methyl cellulose, carboxymethyl cellulose, carboxymethyl hydroxyl guanine, hydroxymethyl cellulose, hydroxyethyl cellulose, carboxyvinyl polymer, polyquaternary ammonium salt, cetyl stearyl alcohol, stearic acid, carrageenan, etc., and one or more of carboxymethyl cellulose, carboxyvinyl polymer, polyquaternary ammonium salt can be preferably used, and carboxyvinyl polymer can be most preferably used.

[0078] In an embodiment of the present application, the cosmetic composition can contain various bases and additives as necessary, and the kind and amount of these components can be easily selected by the inventor. Acceptable additives can be contained as necessary, and for example, components such as preservatives, pigments, additives, etc. of the art can be further contained.

[0079] As a preservative, specifically, phenoxyethanol or 1,2-hexanediol, etc. can be used, and a perfume can be an artificial perfume, etc.

[0080] The additive can be specifically nicotinamide, hydroquinone, balsa extract, arbutin, vitamin C ethyl ether, ascorbic acid glucoside, alpha-bisabolol, ascorbyl tetraisopalmitate, etc. other substances having a whitening function. Nicotinamide can perfect and enhance the whitening effect of the composition by inhibiting the stage in which the already generated melanin moves from the melanocyte to the keratinocyte. Hydroquinone can perfect and enhance the whitening effect of the composition by turning over new skin cells by destroying skin cells. The listed additives such as nicotinamide or hydroquinone can be used together with the composition, thereby perfecting and enhancing the whitening effect of the composition.

[0081] Further, in an embodiment of the present application, the cosmetic composition can contain a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high-molecular peptides, high-molecular polysaccharides, sphingolipids, and seaweed juice. As the formulation ingredients which can be added in addition to the above, oil components, humectants, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjustors, ethanol, pigments, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, and the like can be mentioned.

[0082] In addition, the formulation ingredients which can be added in addition to the above are not limited to the above, and any of the ingredients can be formulated within a range not impairing the object and effects of the present application.

[0083] Further, the cosmetic composition according to an embodiment, as described above, can be used not only as a pharmaceutical composition but also as a food composition. For example, it can be easily used as a main raw material, a sub-raw material, a food additive, a functional food, or a beverage.

[0084] The "food" means a natural substance or a processed product containing one or more nutrients, and preferably means a product which has been processed to a certain extent to be in a state directly edible, and as a general meaning, means all of foods, food additives, functional foods, and beverages.

[0085] As the food to which the food composition can be added, various food categories, beverages, chewing gums, teas, vitamin complexes, and functional foods, for example, can be mentioned. Further, special nutritional foods (e.g., formula milk, baby and infant foods, etc.), meat products, fish meat products, tofu, jellies, noodles (e.g., ramen, noodles, etc.), breads, health auxiliary foods, seasoning foods (e.g., soy sauce, miso, chili sauce, mixed sauce, etc.), sauces, cookies (e.g., snack foods), candies, chocolates, chewing gums, ice creams, dairy products (e.g., fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various pickled vegetables, pickled vegetables), beverages (e.g., fruit beverages, vegetable beverages, soy milk, fermented beverages, etc.), natural seasonings (e.g., ramen seasoning packets, etc.), but are not limited thereto. The food, beverage, or food additive can be prepared by a conventional preparation method.

[0086] In addition, the "functional food" refers to a group of foods in which additional values are given by using physical, biochemical, and biological engineering methods, etc., so that the functions of the foods are expressed in a specific purpose, or foods which are designed to sufficiently express the in vivo regulation functions of the food components related to the regulation of biological defense rhythm, prevention of diseases, recovery from diseases, etc., and are processed, and can be specifically a health functional food. The functional food can include a food-acceptable food adjuvant, and can further include a suitable carrier, excipient, and diluent which are generally used in the preparation of a functional food.

[0087] The type of the health adjuvant food is not limited to this, and can be in the form of a powder, granule, tablet, capsule, or beverage.

[0088] Another embodiment provides a method for whitening skin of an individual, which includes the step of administering the composition to the individual. In the method for whitening skin according to another embodiment, the compound represented by Chemical Formula 1 below has a skin-whitening purpose. As to the composition included in the whitening method, it is as described above.

[0089] [Chemical Formula 1]

[0090]

[0091] In the Chemical Formula 1, each substituent is as defined above.

[0092] The administration can be performed according to a conventional method in the art. The administration can be directly performed to the individual by any means through a route such as intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal, or subcutaneous administration. The administration can be systemic or local administration. The administration can be local administration to a site where skin aging is present. The administration can be performed, for example, by application. The application refers to all methods of contacting the composition to the skin of the individual by a suitable method, whereby the composition can be absorbed into the inside of the skin.

[0093] The individual can be a mammal such as a human, a cow, a horse, a pig, a dog, a sheep, a goat, or a cat. The individual can be an individual who needs to improve, delay, or inhibit excessive pigmentation of the skin. The individual can be an individual who needs to inhibit apoptosis, inhibit protein expression of Tyrosinase, or increase antioxidant activity.

[0094] The administration can be an administration of 0.01 mg to 10,000 mg, 0.1 mg to 1,000 mg, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg, 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg of the composition according to an embodiment per individual per day. Alternatively, the administration can be an administration of the composition according to an embodiment at a working concentration of 0.01 to 25 μM, 0.05 to 5 μM, 0.075 to 3.75 μM, 0.1 to 2.5 μM, 0.15 to 2 μM, 0.25 to 1.5 μM, 0.4 to 1.25 μM, 0.5 to 1.2 μM, or 0.75 to 1.15 μM.

[0095] Advantages, features, and methods of accomplishing the same of the present application will be understood more readily by reference to the following detailed description. The following detailed description is provided to explain certain embodiments of the application. The description is provided to enable those skilled in the art to make and use the application, and is provided in the context of particular embodiments. Numerous specific details are described in order to provide a thorough understanding of the application. However, the description is not intended to limit the scope of the application in any manner.

[0096] (Example)

[0097] Test Example 1: Whitening efficacy test using melanocytes

[0098] Melanocytes isolated from normal human skin were treated in a medium having a final concentration of 0.1 μM, 1 μM, 10 μM, or 50 μM of a compound represented by Chemical Formula 1 below, which was dissolved in DMSO at 1,000X. The medium in which the mixture was dissolved was replaced every 2 days, and the cells were grown in an incubator at 37°C under 5% CO2 for a maximum of 6 days. After the experiment, the cells were lysed in 1N NaOH, and the absorbance was measured at 475 nm to compare the relative amount of melanin. In addition, proteins were isolated from the cells, and the expression amount of tyrosinase was confirmed by western blotting. Then, the proteins were quantified to compare the amount of cells (cell viability).

[0099] [Chemical Formula 1-1]

[0100]

[0101] In Figures 1 to 4 The results of Test Example 1 are shown in Table 1.

[0102] Figure 1 The amount of melanin production according to the concentration of the compound represented by Chemical Formula 1-1 and whether there is ultraviolet light is shown. As such, when the compound represented by Chemical Formula 1-1 is treated into melanin-producing cells, it can be confirmed that the production of melanin is statistically significantly inhibited under all conditions without ultraviolet light and with ultraviolet light.

[0103] Figure 2 The melanin-producing cells cultured in Test Example 1 are shown to be contained in the same amount of e-tube (not treated with ultraviolet light). This indicates that the cell suspension containing the same amount of melanin-producing cells according to the concentration of the compound represented by Chemical Formula 1-1. It can be confirmed that as the concentration of the compound represented by Chemical Formula 1-1 increases, the color of the melanin-producing cells becomes brighter. The brighter the color of the melanin-producing cells, the less the amount of melanin production, and thus, it can be confirmed that when the compound represented by Chemical Formula 1-1 is treated into melanin-producing cells, the production of melanin is inhibited.

[0104] Figure 3 The amount of melanin-producing cells according to the concentration of the compound represented by Chemical Formula 1-1 and whether there is ultraviolet light is shown. Figure 3 In Table 2, it can be confirmed that the number of melanin-producing cells is reduced by about half when the melanin-producing cells are treated with ultraviolet light, at the same time, when considering that Figure 1 In Table 2, at the point where there is only a difference in whether there is ultraviolet light and all other conditions are the same, the amount of melanin production is almost similar, it can be confirmed that when ultraviolet light is treated, the amount of melanin production in each melanin-producing cell is increased by about 2 times.

[0105] On the contrary, when the melanin-producing cells are treated with ultraviolet light (treated with the compound represented by Chemical Formula 1-1), the number of melanin-producing cells is almost constant, at the same time, when considering that Figure 1 In Table 2, at the point where there is only a difference in whether there is ultraviolet light and all other conditions are the same, the amount of melanin production is almost similar, it can be confirmed that when ultraviolet light is treated, the amount of melanin production in each melanin-producing cell is not changed.

[0106] As such, it can be confirmed that the compound represented by Chemical Formula 1-1 inhibits the increase in the amount of melanin production in each melanin-producing cell when ultraviolet light is treated.

[0107] As such, it can be confirmed that the compound represented by Chemical Formula 1-1 inhibits the increase in the amount of melanin production in each melanin-producing cell when ultraviolet light is treated.Figure 4 The expression amount of tyrosinase as a melanin production enzyme according to the concentration of the compound represented by Chemical Formula 1-1 and whether or not there is ultraviolet light was shown. As a control group, the expression amount of GAPDH was confirmed. By Figure 4 , it was confirmed that the expression of tyrosinase was reduced regardless of whether or not there is ultraviolet light when the compound represented by Chemical Formula 1-1 was treated.

[0108] In summary Figures 1 to 4 As a result, it was confirmed that the compound represented by Chemical Formula 1-1 inhibits the expression of tyrosinase as a melanin production enzyme, and inhibits the production of melanin regardless of whether or not there is ultraviolet light, and has a whitening effect.

[0109] Test Example 2: Whitening effect experiment using artificial skin

[0110] The experiment was performed using MEL-300-B (MatTek, USA). The compound represented by Chemical Formula 1-1 was dissolved in DMSO at 1000X, and was put into the medium to be treated to have a final concentration of 0.1, 1, 50 μM. The medium in which the test substance was dissolved was replaced every 2 days, and the artificial skin was grown in an incubator at 37°C, 5% CO2 for 2 weeks. Finally, a photograph of the artificial skin was taken, and the L value was calculated. The relative Δ (delta) L value was calculated by the formula shown below. The larger the relative ΔL value, the brighter the skin color.

[0111] Relative ΔL value = (control 0 day, L value - control 14 day, L value) - (7DHC 0 day, L value - 7DHC 14 day, L value)

[0112] Figure 5 The results of Test Example 2 are shown in Table 1.

[0113] Figure 5 The relative ΔL value according to whether or not the compound represented by Chemical Formula 1-1 is contained and the concentration is shown. Kojic acid 1% was used as a positive control group. By Figure 5 , it was confirmed that the skin color became brighter when the compound represented by Chemical Formula 1-1 was treated, compared to the control group (NT).

[0114] While the preferred embodiments of the present application have been described above, the scope of the present application is not limited thereto, and various modifications and improvements made by those skilled in the art using the basic concept of the present application defined in the claims belong to the scope of the present application.

Claims

1.Use of a compound represented by the following Chemical Formula 1-1 for preparing a composition for whitening: 【Chemical Formula 1-1】 2.The use according to claim 1, wherein: the compound represented by the Chemical Formula 1-1 is contained in a concentration of 0.1 µM to 1 mM with respect to the total amount of the composition for whitening. 。 3.The use according to claim 1, wherein: the compound represented by the Chemical Formula 1-1 is contained in a concentration of 1 µM to 50 µM with respect to the total amount of the composition for whitening. 4.The use according to claim 1, wherein: the composition for whitening is a cosmetic composition. 5.A method of whitening skin of a subject for non-therapeutic purposes, the method of whitening skin of a subject for non-therapeutic purposes comprising the step of applying to the subject a cosmetic composition containing, as an effective ingredient, a compound represented by the following Chemical Formula 1-1: 【Chemical Formula 1-1】 6.The method of whitening skin of a subject for non-therapeutic purposes according to claim 5, wherein: the compound represented by the Chemical Formula 1-1 is contained in a concentration of 0.1 µM to 1 mM with respect to the total amount of the composition for whitening. 7.The method of whitening skin of a subject for non-therapeutic purposes according to claim 5, wherein: the compound represented by the Chemical Formula 1-1 is contained in a concentration of 1 µM to 50 µM with respect to the total amount of the composition for whitening. ​ ​ ​ 。 ​ ​ ​ ​

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