CN115212121A - Use of compound for preparing whitening composition and skin whitening method using the same - Google Patents

Abstract

There are provided a use of a compound represented by the following chemical formula 1 for preparing a whitening composition and a skin whitening method of a subject including the step of administering the compound to the subject, herein: [ chemical formula 1 ]

In the chemical formula 1, each substituent is as defined in the specificationAs defined.

Description

Use of compound for preparing whitening composition and skin whitening method using the same

Technical Field

The present disclosure relates to the use of a compound for preparing a whitening composition and a skin whitening method using the same.

Background

The skin serves a variety of functions necessary for human survival. Barrier function for maintaining the internal homeostasis of the human body to correspond to environmental changes, sensory function for sensing external changes, thermoregulation function, etc. are the most representative skin functions. Among the various skin functions, particularly the barrier function of the skin is mainly embodied by the stratum corneum, which is located at the outermost layer of the skin. It has been reported that the stratum corneum not only simply functions as a barrier but also affects the function, action, structure, and the like of the cell layer existing inside, that is, the epidermis layer or the dermis layer, and thus the importance thereof 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 water from the inside. In addition, keratinocytes of the stratum corneum form a skin barrier through differentiation and keratinization processes.

The epidermis including the stratum corneum can be divided into stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum and stratum basale. Melanin is present on the basal layer, which is the lowest layer of the epidermis. Melanin is a brown pigment contained in tissues such as skin and eyes, and is produced by melanin-forming cells.

Melanin-expressing genes vary from person to person, and thus regulate the amount of melanin to determine skin color. That is, the more the amount of melanin, the darker the skin color and the like. Specifically, the amount of melanin is determined by the number, concentration, melanin secretion ability, and the like of melanosomes in melanin-forming cells, and the skin color is determined by the factors.

Melanin has a function of blocking a certain amount or more of ultraviolet rays, thus maintaining the body temperature of the skin and protecting the skin from ultraviolet rays. Melanin can also block ultraviolet rays penetrating the skin, but when the skin is exposed to ultraviolet rays for a long time, melanin-forming cells are stimulated to increase the amount of melanin production. The melanin pigment thus produced migrates to the horny layer of the skin and deposits on the horny layer, causing a pigmentation phenomenon. The pigmentation phenomenon occurring on the skin includes chloasma, freckles, spots, and the like.

Melanin is a macromolecule formed by the oxidation of tyrosine protein by tyrosinase. Therefore, the production of melanin can be prevented as long as the activity of tyrosinase or the oxidation of tyrosine is prevented. In addition, pigmentation can be prevented by preventing the produced melanin from accumulating on the horny layer. The inhibition of pigmentation is also directly related to lightening of skin color, thereby whitening skin, during which the interest in preventing and improving pigmentation is increasing, and many efforts are being made to develop whitening functional products.

[ Prior art documents ]

(patent document 0001) Japanese laid-open patent No. 2008-534619 (publication No. 2008.08.28)

Disclosure of Invention

Technical problem

An embodiment is intended to provide use of a compound for preparing a whitening composition, which can impart an excellent whitening effect to the skin by inhibiting the expression of a protein, which is a melanogenic enzyme, to inhibit the production of melanin.

Another embodiment is directed to a method of whitening skin of an individual, including the step of administering the cosmetic composition to the individual.

Technical scheme

According to an embodiment, there is provided a use of a compound represented by the following chemical formula 1 for preparing a whitening composition.

[ chemical formula 1 ]

In the chemical formula 1, the reaction mixture is,

R ₁ to R ₄ Each independently is 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, R ₁ To R ₃ At least one of (A) is methyl。

May be, said R ₁ To R ₃ Each independently is methyl, the R ₄ Is isoamyl, and X is hydroxyl.

The compound represented by the chemical formula 1 may be contained at a concentration of 0.1 μ M to 1mM with respect to the total amount of the whitening composition.

The compound represented by the chemical formula 1 may be contained at a concentration of 1 μ M to 50 μ M with respect to the total amount of the whitening composition.

The whitening composition may be a cosmetic composition or a food composition.

According to another embodiment, there is provided a method of whitening skin of a subject, the method including the step of administering a cosmetic composition containing the compound represented by chemical formula 1 as an active ingredient to the subject.

According to still other embodiments, there is provided a use of the compound represented by the chemical formula 1 for preparing a whitening composition.

According to still other embodiments, there is provided a method of applying a composition containing the compound represented by chemical formula 1 to skin, thereby whitening the skin.

The compounds and concentrations for the compound represented by the chemical formula 1 may be as described above.

Effects of the invention

The composition according to an embodiment can provide an excellent whitening effect to skin coated with the composition by inhibiting the production of melanin by inhibiting the expression of a protein, which is a melanin-producing enzyme.

Drawings

FIG. 1 is a graph showing melanin production amounts according to concentrations of compounds represented by chemical formula 1-1 and the presence or absence of ultraviolet rays;

FIG. 2 is a photograph showing a suspension of melanin generating cells according to the concentration of the compound represented by chemical formula 1-1;

FIG. 3 is a graph showing the amount of melanin-producing cells according to the concentration of the compound represented by chemical formula 1-1 and the presence or absence of ultraviolet rays;

FIG. 4 is a graph showing an expression amount of tyrosinase as a melanin-producing enzyme according to the concentration of the compound represented by chemical formula 1-1 and the presence or absence of ultraviolet rays;

fig. 5 is a graph showing the relative Δ L values according to the presence or absence of the compound represented by chemical formula 1-1 and the concentration.

Detailed Description

Hereinafter, embodiments of the present invention will be described in detail so that those having ordinary knowledge in the art to which the present invention pertains can easily carry out the present invention. However, the present invention may be realized in various forms and is not limited to the embodiments described herein.

In the present specification, the improvement of skin whitening function means brightening and whitening the color of the stratum corneum located in the outer layer of the skin. The stratum corneum, the first membrane of the skin, can be easily damaged by the external environment. In order to impart whitening ability to the skin, the problem can be solved temporarily by a prescription of applying an external preparation for skin, but it is difficult to solve the fundamental problem, and further, since the external preparation for skin mostly has an effect of simply masking the degree of blackness in the skin without solving the problem, the pigmentation problem of the skin cannot be fundamentally improved by a prescription of simply applying an external preparation for skin. For this reason, the present inventors confirmed that the compound represented by a specific chemical formula constituting the composition according to an embodiment can solve the fundamental problems as described above, thereby fundamentally improving skin whitening efficacy, thereby completing the present invention.

More specifically, the composition according to an embodiment may be expected to have skin whitening effects by regulating signal transduction with respect to the expression of melanin-producing enzyme (tyrosinase), which is involved in melanin synthesis.

In response to this, the fact that melanin production is increased when the intracellular concentration of c-AMP is increased, and that melanin production is decreased when the extracellular signal-regulated kinase (ERK) transduction pathway is activated, has been published. However, as a method for activating the extracellular signal-regulated kinase transduction pathway, a method of stimulating a signal transduction pathway that phosphorylates an extracellular signal-regulated kinase is known, and recently, when protein phosphatase 2A (protein phosphatase 2a, pp2a) that is an enzyme that dephosphorylates an extracellular signal-regulated kinase is inhibited, the activation of the extracellular signal-regulated kinase is expected to eventually obtain a skin whitening effect by the decomposition of Microphthalmia-associated transcription factor (MIITF), but an effective method for inhibiting the protein phosphatase 2A has not been disclosed recently.

In response to this, the present inventors have confirmed that a composition containing a specific compound as an active ingredient in a specific concentration range has an effect of inhibiting the synthesis of melanin-producing enzyme (tyrosinase), and have completed the present invention.

On the other hand, as described above, since a substance that directly inhibits melanogenesis enzyme (tyrosinase) needs to be used at a high concentration, it not only can exhibit side effects such as skin irritation, but also kojic acid (kojic acid) is in a state of being prohibited from being used because of the possibility that kojic acid can cause skin cancer. However, the composition according to an embodiment does not directly inhibit the melanogenesis enzyme (tyrosinase), and thus does not irritate the skin and hardly has side effects, and can exhibit a very strong whitening effect by inhibiting the production of the melanogenesis enzyme (tyrosinase).

In this specification, when a layer, a film, a region, a plate, or the like is referred to as being partially "on" other portions, it includes not only a case where "directly" on "the other portions but also a case where still other portions are present therebetween. In contrast, when a portion is referred to as being "directly on" another portion, it is intended that no other portion is present in the middle.

In the present specification, unless otherwise defined, "combination" means mixing or copolymerization. The term "copolymerization" means block copolymerization or random copolymerization, and the term "copolymer" means block copolymer or random copolymer.

Hereinafter, a skin whitening composition according to an embodiment is described.

The use of a compound represented by the following chemical formula 1 according to an embodiment is used to prepare a composition for skin whitening.

[ chemical formula 1 ]

In the chemical formula 1, the first and second organic solvents,

R ₁ to R ₄ Each independently is 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, R ₁ To R ₃ At least one of which is methyl.

For example, in the chemical formula 1, R may be ₁ To R ₃ Each independently of the other being methyl, R ₄ Is isoamyl and X is hydroxyl.

The compound represented by the chemical formula 1 can impart a whitening effect to the skin by blocking an increase in the expression of tyrosinase (tyrosinase), which is a melanin-producing enzyme.

The hyperpigmentation of the skin may be caused by various factors such as abnormal hormones in the body after the inflammatory reaction of the skin, genetic diseases, and ultraviolet irradiation, and the main factors include abnormal melanin synthesis and abnormal distribution.

The main function of melanin is to remove oxygen radicals, thereby protecting the skin from damage caused by oxygen radicals. Therefore, melanin is often indicated to have an effective system for protecting the skin from physical and chemical toxic substances. The production of melanin as described above is completed by the action of an enzyme and a spontaneous oxidation reaction after Tyrosine (Tyrosine) is converted into Dopaquinone (Dopaquinone) by a melanin-producing enzyme (Tyrosine) in a melanocyte.

The methods for inhibiting melanin production known so far are roughly as follows.

First, it is a method of blocking ultraviolet rays to remove a main cause of melanin production. This method can be expected to have an excellent effect by incorporating a light scattering agent or a light blocking agent into the cosmetic composition.

Then, melanin production can be inhibited by blocking the synthesis of a core carbohydrate required in the activity of melanin-producing enzyme (tyrosinase), for example, glucosamine (Glucosamine).

In addition, the function of melanin-producing enzyme (Tyrosinase), which is an enzyme involved in the production of melanin by Kojic acid or arbutin, can be inhibited.

Further, substances having specific toxicity to melanocytes which produce melanin pigment, such as hydroquinone (hydroquinone), may be used to inhibit the division of melanocytes.

In addition, a method of decoloring melanin formed by reduction has been described.

At present, most of the studies for finding a whitening composition have focused on a substance that directly inhibits melanogenesis enzyme (tyrosinase) involved in melanin synthesis. However, in addition to direct inhibition of melanogenesis enzyme (tyrosinase), a technique has been proposed in which whitening effect can be expected by regulating signal transduction (signal transduction) involved in the expression of melanogenesis enzyme (tyrosinase) (Briganti S, camera E, picardo m. Pigment Cell Res,2003,16 (2): 101-10).

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 affected by external stimuli, hormones, or the like (DS Kim, ES Whang, JE Lee, SY, SB Kwon, and KC park.J Cell Sci.2003;116 1699-706), but a method of reducing the production of melanin by inhibiting the expression of MITF has not been introduced yet.

The composition according to an embodiment reduces the production of melanin, and in particular, has an excellent effect of blocking an increase in protein expression of tyrosinase (tyrosinase) as a melanin-producing enzyme in a melanin-producing cell (melanocyte). 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 in which pigmentation occurs, very excellent skin whitening effects can be expected.

In the chemical formula 1, a substituent or a part of the hydrogen atoms bonded to the matrix is specified in a steric arrangement structure (configuration), and having the steric arrangement structure as described above can greatly improve the skin whitening effect.

One embodiment provides a use of the compound represented by chemical formula 1 for preparing a whitening composition, which may contain the compound represented by chemical formula 1 alone or include one or more pharmaceutically acceptable carriers, excipients, or diluents in a pharmaceutically effective amount.

The compound represented by chemical formula 1 may be contained in the composition at a concentration of 0.1 μ M to 1mM, for example, at a concentration of 1 μ M to 50 μ M, relative to the total amount of the whitening composition. When the compound represented by the chemical formula 1 is used at a concentration of less than 0.1 μ M, the phenomenon of increasing the protein expression of melanogenic enzyme (tyrosinase) in melanogenic cells (melanocytes) is suppressed to a weak extent, and thus the skin whitening function improving effect cannot be obtained, and the skin whitening function improving effect may be only weak at a concentration of less than 1 μ M.

In addition, when the compound represented by chemical formula 1 is used at a concentration exceeding 1mM, there may be no large difference in skin whitening effect compared to the case where the compound represented by chemical formula 1 is contained at a concentration of 0.1 μ M to 1mM, but rather the compound represented by chemical formula 1 is unnecessarily excessively contained, and thus there may be a possibility of limiting the effects of other functional components in the composition, and the like, and thus it may be not preferable.

The above "pharmaceutically effective amount" means an amount sufficient to exhibit the desired physiological or pharmacologically active activity by administering the physiologically active ingredient to an animal or human. However, the pharmaceutically effective amount may be appropriately changed depending on the degree of symptoms, the age, body weight, health state, sex, administration route, treatment time, and the like of the patient.

In addition, the above "pharmaceutically acceptable" means that it is physiologically acceptable and does not generally cause allergic reactions such as gastrointestinal disorders, dizziness or the like when administered to humans. Examples of the carrier, excipient, and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginic acid, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition, a filler, an anticoagulant, a lubricant, a wetting agent, a perfume, an emulsifier, a preservative, and the like may be contained.

For example, the composition may be a cosmetic composition.

In the present specification, the "cosmetic material" may mean any material having not only a cosmetic function but also a medical function in addition to the cosmetic function.

The formulation of the cosmetic composition is not particularly limited and may be appropriately selected according to the purpose.

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

More specifically, the composition can be formulated into cosmetic compositions such as cleaning agent, nutrient solution (tonic), hair styling agent, nutrient lotion, essence emulsion, hair treatment agent, hair cream, shampoo, emulsion, hair tonic, or hair dye; base cosmetics of oil-in-water (O/W) type, water-in-oil (W/O) type, and the like. For example, the composition may have one dosage form selected from the group consisting of a skin lotion, an astringent, an emulsion, a milk emulsion, a moisturizing emulsion, a nourishing emulsion, a massage cream, a nourishing cream, a moisturizing cream, a hand cream, an ointment, a foundation, an essence, a nourishing essence, a mask, a soap, a cleansing foam, a cleansing milk, a cleansing cream, a body lotion, a bath lotion, an emulsion, an ointment, a gel, a cream, a patch, and a spray.

In addition, in each dosage form of the composition, other components than the essential components described above may be selected and formulated as appropriate by those skilled in the art according to the kind of other external preparations or the purpose of use. For example, ultraviolet blocking agents, hair conditioning agents, perfumes, and the like may also be included.

The cosmetic composition may contain a cosmetically acceptable medium or base. It can be provided, as all formulations suitable for topical use, for example in the form of solutions, gels, anhydrous products in solid or paste form, emulsions obtained by dispersing an oily phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules or dispersions of ionic (liposomes) and/or nonionic encapsulates, or in the form of creams, lotions, emulsions, powders, ointments, sprays or concealer sticks. The compositions may be prepared according to conventional methods in the art.

When the formulation of the present invention is a solution or emulsion, as a carrier component, a solvent, solubilizer or demulsifier, for example, water, ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butylene glycol oil, glycerin fatty ester, polyethylene glycol or fatty acid ester of sorbitol is used.

When the dosage form of the present invention is a suspension, as a carrier ingredient, a liquid diluent such as water, ethanol or propylene glycol; suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters, and polyoxyethylene sorbitan esters; microcrystalline cellulose; aluminum metahydroxide; bentonite, agar, or tragacanth.

When the dosage form of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or the like can be used as a carrier component.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, when the formulation is a spray, a propellant such as chlorofluorocarbon, propane/butane or dimethyl ether may be contained.

In one embodiment of the present invention, the cosmetic composition may further contain a thickener. The thickener contained in the cosmetic composition of the present invention may be methylcellulose, carboxymethylcellulose, carboxymethyl hydroxyguanine, hydroxymethylcellulose, hydroxyethylcellulose, a carboxyvinyl polymer, a polyquaternary ammonium salt, cetostearyl alcohol, stearic acid, carrageenan, or the like, and preferably one or more of carboxymethylcellulose, a carboxyvinyl polymer, and a polyquaternary ammonium salt, and most preferably a carboxyvinyl polymer.

In one embodiment of the present invention, the cosmetic composition may contain various bases and additives as needed, and the kinds and amounts of these components can be easily selected by the inventors. Acceptable additives may be contained as necessary, and for example, components such as preservatives, pigments, additives and the like which are conventional in the art may also be contained.

As the preservative, phenoxyethanol (Phenoxythane) or 1,2-Hexanediol (1, 2-Hexanediol) can be mentioned, and as the perfume, artificial perfume or the like can be mentioned.

The additive can be selected from nicotinamide, hydroquinone, broussonetia extract, arbutin, vitamin C ethyl ether, ascorbyl glucoside, alpha-bisabolol, ascorbyl tetraisopalmitate, etc. Niacinamide can improve and enhance the whitening efficacy of the composition by inhibiting the stage of melanin production that has already been produced from melanoblasts to keratinocytes. Hydroquinone can rejuvenate (turn over) new skin cells by destroying them, thereby perfecting and enhancing the whitening efficacy of the composition. The listed additives, such as niacinamide or hydroquinone, can be used with the composition to complement and enhance the whitening efficacy of the composition.

In addition, in one embodiment of the present invention, the cosmetic composition may 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. Examples of the compounding ingredients that can be added in addition to the above-mentioned ingredients include oil and fat ingredients, moisturizers, lubricants (emulsifiers), surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH regulators, ethanol, pigments, perfumes, blood circulation improvers, cooling agents, antiperspirants, purified water and the like.

The other ingredients to be added are not limited to these, and any of the above-mentioned ingredients may be added within a range not to impair the object and effect of the present invention.

Further, the cosmetic composition according to an embodiment may be used not only as a pharmaceutical composition but also as a food composition, as described above. For example, it can be easily used as a main material, an auxiliary material, a food additive, a functional food or a beverage for food.

The term "food" refers to a natural product or processed product containing one or more nutrients, preferably a state that can be directly eaten after a certain degree of processing steps, and includes all foods, food additives, functional foods, and beverages as a general meaning.

Examples of foods to which the food composition can be added include various foods, beverages, chewing gums, teas, vitamin complexes, and functional foods. Further, special nutritional foods (e.g., powdered formula, infant food, and baby food), meat products, fish products, tofu, bean jelly, noodles (e.g., noodles, and the like), bread, health supplementary foods, seasoned foods (e.g., soy sauce, doenjang, chili paste, sauce mix, and the like), sauce, cookies (e.g., snacks), candies, chocolate, chewing gum, ice cream, dairy products (e.g., fermented milk, cheese, and the like), other processed foods, kimchi, pickled foods (various pickles, pickles), beverages (e.g., fruit drinks, vegetable drinks, bean milk, fermented beverages, and the like), natural seasonings (e.g., a seasoning pack for noodles, and the like), but not limited thereto, are included. The food, drink or food additive can be prepared by a conventional preparation method.

The "functional food" is a group of foods that are added with value by physical, biochemical, and biological engineering methods to make the functions of the foods function and express for a specific purpose, or a food that is designed to sufficiently express the in vivo regulatory functions of food components related to the regulation of the biological defense rhythm, prevention of diseases, recovery from diseases, and the like, and to be processed, and may be specifically a health functional food. The functional food may include a dietetically acceptable supplementary food additive, and may further include suitable carriers, excipients and diluents generally used in the preparation of functional foods.

The health supplementary food is not limited thereto, and may be in the form of powder, granule, tablet, capsule, or beverage.

Another embodiment provides a method of whitening skin of a subject, comprising the step of administering the composition to the subject. In a skin whitening method according to another embodiment, a compound represented by the following chemical formula 1 has a skin whitening effect. The composition included in the whitening method is as described above.

[ chemical formula 1 ]

In the chemical formula 1, each substituent is as defined above.

The administration may be according to conventional methods in the art. The administration can be by any means directly to the individual, for example, by intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal (int ratracheal) or subcutaneous administration. The administration may be systemic or local. The administration may be topical administration to a site where skin aging is present. The administration may be, for example, by coating. By application is meant all methods of contacting the composition to the skin of an individual by suitable means whereby the composition can be absorbed into the skin.

The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat or cat. The subject may be a subject in need of improvement, delay or inhibition of skin hyperpigmentation. The subject may be a subject in need of inhibition of apoptosis, inhibition of melanogenesis enzyme (Tyrosinase) protein expression, or increased antioxidant activity.

The administration may be daily administration of 0.01mg to 10000mg, 0.1mg to 1000mg, for example 0.1mg to 500mg, 0.1mg to 100mg, 0.1mg to 50mg, 0.1mg to 25mg, 1mg to 1000mg, 1mg to 500mg, 1mg to 100mg, 1mg to 50mg, 1mg to 25mg, 5mg to 1000mg, 5mg to 500mg, 5mg to 100mg, 5mg to 50mg, 5mg to 25mg, 10mg to 1000mg, 10mg to 500mg, 10mg to 100mg, 10mg to 50mg or 10mg to 25mg of the composition according to an embodiment to each individual. Alternatively, the administration may be an administration in which the composition according to an embodiment acts at a concentration (working composition entry) of 0.01 to 25 μ M, 0.05 to 5 μ M, 0.075 to 3.75 μ M, 0.1 to 2.5 μ M, 0.15 to 2 μ M, 0.25 to 1.5 μ M, 0.4 to 1.25 μ M, 0.5 to 1.2 μ M, or 0.75 to 1.15 μ M.

The advantages, features, and methods of attaining them of the invention will become apparent by reference to the embodiments described in detail below. Hereinafter, the invention of the present application will be described in detail by examples. However, the examples are intended to specifically illustrate the present invention, and the scope of the present invention is not limited by the examples.

(examples)

Test example 1: whitening efficacy test Using melanogenic cells

Melanogenic cells (melanocytes) isolated from normal skin of human are put into a culture medium in which a compound represented by the following chemical formula 1 is dissolved in DMSO at 1000X to have final concentrations of 0.1 μ M, 1 μ M, 10 μ M, 50 μ M for treatment. Replacing the medium in which the mixture is dissolved every 2 days and at 37 ℃, 5% CO ₂ The incubator of (1) allows cells to grow for up to 6 days. After the experiment was completed, the cells were lysed to 1NIn NaOH, absorbance was measured at 475nm, and the relative melanin amounts were compared. In addition, proteins were isolated from the cells, and the expression level of tyrosinase (tyrosinase) was confirmed by the western blotting method. Then, the protein was quantified to compare the amount of cells (cell viability).

[ chemical formula 1-1 ]

The results of test example 1 are shown in fig. 1 to 4.

Fig. 1 shows the amount of melanin production according to the concentration of the compound represented by the chemical formula 1-1 and the presence or absence of ultraviolet rays. Thus, when the compound represented by the above chemical formula 1-1 was treated in melanogenesis cells, it was confirmed that the melanogenesis was statistically significantly inhibited under both the ultraviolet-free condition and the ultraviolet-containing condition.

FIG. 2 shows that the melanogenesis cells cultured in the test example 1 were filled with the same amount of e-tube (untreated UV). It represents a cell suspension (cell suspension) containing the same number of melanogenic cells according to the concentration of the compound represented by the chemical formula 1-1. It can be confirmed that the color of the melanogenesis cells becomes bright as the concentration of the compound represented by the chemical formula 1-1 increases. The brighter the color of the melanogenic cells, the less amount of melanin production was indicated, and therefore, it was confirmed that the production of melanin was inhibited when the compound represented by the above chemical formula 1-1 was treated in the melanogenic cells.

FIG. 3 shows the amount of melanogenesis cells according to the concentration of the compound represented by chemical formula 1-1 and the presence or absence of ultraviolet rays. In fig. 3, it was confirmed that the control group reduced the number of melanocytes by about half when the melanocytes were treated with ultraviolet rays, and at the same time, when considering the point in fig. 1 that the melanin production amounts were almost similar only when there was a difference in the ultraviolet rays but the other conditions were all the same, it was confirmed that the melanin production amount per melanocyte increased by about 2 times when the ultraviolet rays were treated.

In contrast, when the melanin generating cells were treated with ultraviolet rays (treated with the compound represented by the above chemical formula 1-1), the number of the melanin generating cells was almost constant, and at the same time, when considering that the melanin generation amounts were almost similar only when there was a difference in the presence or absence of ultraviolet rays and the other conditions were all the same in fig. 1, it was confirmed that the melanin generation amount in each melanin generating cell was not changed when the ultraviolet rays were treated.

From this, it was confirmed that the compound represented by the above chemical formula 1-1 inhibited the increase of melanin production per melanin producing cell when it was treated with ultraviolet rays.

FIG. 4 shows the expression amount of tyrosinase, which is a melanin production enzyme, according to the concentration of the compound represented by the chemical formula 1-1 and the presence or absence of ultraviolet rays. As a control group, the expression level of GAPDH was confirmed. From FIG. 4, it can be confirmed that the expression of tyrosinase was reduced regardless of the presence or absence of ultraviolet rays when the compound represented by the chemical formula 1-1 was treated.

As a result of combining the results of fig. 1 to 4, it was confirmed that the compound represented by the chemical formula 1-1 inhibited the expression of tyrosinase, which is a melanin production enzyme, and inhibited the production of melanin regardless of the presence or absence of uv light, thereby having whitening effects.

Test example 2: whitening efficacy test using artificial skin

Experiments were carried out using MEL-300-B (MatTek, USA). The compound represented by the chemical formula 1-1 was dissolved in DMSO at 1000X, and placed in a culture medium to be treated so that the final concentration was 0.1, 1, 50 μ M. The culture medium with the test substances dissolved therein was replaced every 2 days and the content of CO was 5% at 37 ℃% ₂ The artificial skin is grown in the incubator for 2 weeks. Finally, a picture of the artificial skin is taken, and the L value is obtained. The relative Δ (delta) L value (relative Δ L value) is obtained by the following formula. A larger value of the relative Δ L indicates a brighter skin color.

Relative Δ L value = (0-day L value of control group-14-day L value of control group) - (0-day L value of 7 DHC-14-day L value of 7 DHC) (Relative Δ L value = (control 0day, L value-control 14day, L value) - (7 DHC 0day, L value-7DHC 14day, L value))

The results of test example 2 are shown in fig. 5.

Fig. 5 shows relative Δ L values according to the presence or absence and concentration of the compound represented by the chemical formula 1-1. Kojic acid 1% (Kojic acid 1%) was used as a positive control group. From FIG. 5, it was confirmed that the skin color was brighter when the compound represented by the chemical formula 1-1 was treated than the control group (NT).

The preferred embodiments of the present invention have been described in detail, but the scope of the appended claims is not limited thereto, and various modifications and improvements by those skilled in the art using the basic concept of the present invention defined in the claims are also within the scope of the appended claims.

Claims (9)

1. Use of a compound represented by the following chemical formula 1 for preparing a whitening composition:

[ chemical formula 1 ]

In the chemical formula 1, the first and second organic solvents,

R ₁ to R ₄ Each independently is 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;

R ₁ to R ₃ At least one of which is methyl.

2. The use according to claim 1, wherein:

said R is ₁ To R ₃ Each independently is methyl;

the R is ₄ Is isoamyl;

and X is hydroxyl.

3. Use according to claim 1, wherein:

the compound represented by the chemical formula 1 is contained at a concentration of 0.1 μ M to 1mM with respect to the total amount of the whitening composition.

4. Use according to claim 1, wherein:

the compound represented by the chemical formula 1 is contained at a concentration of 1 to 50 μ M with respect to the total amount of the whitening composition.

5. Use according to claim 1, wherein:

the whitening composition is a cosmetic composition or a food composition.

6. A skin whitening method of a subject, the skin whitening method comprising the step of administering to the subject a cosmetic composition containing a compound represented by the following chemical formula 1 as an active ingredient:

[ chemical formula 1 ]

In the chemical formula 1, the reaction mixture is,

R ₁ to R ₄ Each independently is 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;

R ₁ to R ₃ At least one of which is methyl.

7. The method of skin whitening of an individual according to claim 6, wherein:

said R is ₁ To R ₃ Each independently is methyl;

the R is ₄ Is isoamyl;

and X is hydroxyl.

8. The method of skin lightening of an individual according to claim 6, wherein:

the compound represented by the chemical formula 1 is contained at a concentration of 0.1 μ M to 1mM with respect to the total amount of the whitening composition.

9. The method of skin lightening of an individual according to claim 6, wherein:

the compound represented by the chemical formula 1 is contained at a concentration of 1 to 50 μ M with respect to the total amount of the whitening composition.

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