KR101083247B1 - Hypopigmenting Composition Comprising FTY720 As an Active Ingredient - Google Patents

Abstract

The present invention relates to novel whitening uses of FTY720 or derivatives thereof, which are already known for use in immunosuppressants and in the treatment of multiple sclerosis. More specifically, the present invention relates to a whitening cosmetic composition comprising FTY720 or a derivative thereof as an active ingredient and a pharmaceutical composition for the treatment or prevention of hyperpigmentation disease. FTY720, an active ingredient of the composition of the present invention, exhibits a very good whitening effect by inhibiting the synthesis of melanin and the expression of tyrosinase.

FTY720, melanin production, β-catenin, MITF (microphthalmia associated transcription factor), inhibitory tyrosinase activity, cosmetic composition for whitening

Description

Hypopigmenting Composition Comprising FTY720 As an Active Ingredient}

The present invention relates to novel whitening applications of FTY720 or derivatives thereof. More specifically, the present invention relates to a whitening cosmetic composition comprising FTY720 or a derivative thereof as an active ingredient and a pharmaceutical composition for the treatment or prevention of hyperpigmentation disease.

Pigments that determine skin color include melanin, hemoglobin and carotenoids, and various colors such as human skin, hair, and eyes are determined by these pigments. The most important pigment for determining the color of the skin is melanin, the skin color is determined according to the nature and distribution of melanin.

In humans, the pigments in the skin or hair protect against the harmful effects of sunlight, especially ultraviolet light. For example, people with poor pigmentation (Albinos) are very sensitive to sunlight and are susceptible to burns, and are more likely to develop skin cancer even at a young age. Short wavelength ultraviolet light (290-320 nm) and carcinogens form oxygen radicals in the skin, which are known to attack skin cells and age the skin.

The main function of melanin is to remove oxygen radicals and protect the skin from damage caused by it. Therefore, high levels of melanin mean that it has an effective response system to protect the skin from physical and chemical toxic substances. However, from the aesthetic point of view of humans, freckles, blemishes, etc. due to melanin deposition are negative factors.

Factors that promote the production of melanin include factors such as estrogen, prostaglandin, as well as sunlight (ultraviolet rays). The production and disappearance cycle of melanin is as follows. When melanocytes are stimulated, the amino acid tyrosine contained in the cell combines with tyrosinase, which is activated by stimulation, to produce melanosomes. In this case, tyrosine is combined with oxygen and oxidized, and tyrosinase is combined with copper. If the skin lacks copper, it interferes with normal melanin production. Stimulation, such as UV, directly affects melanin-producing cells, and also affects melanocyte stimulating hormone (MSH), which stimulates melanin production when melanocyte stimulating hormone secretion increases in the medulla. The amino acid tyrosine contained in the melanocytes is converted into dopa by the action of tyrosinase, and then into dopa-quinone by the action of dopaoxidase to produce melanin. The melanin thus produced is circulated to be delivered to the skin cells and the melanin is lost and disappeared along with the epidermal detachment.

The method of inhibiting melanin production in whitening cosmetics can be divided into the following. First, a method of removing the main cause of melanin production by blocking ultraviolet rays, this method may contain a light scattering agent or a light blocking agent as a cosmetic composition can expect the desired result. Second, it is a method of inhibiting melanin production by inhibiting the synthesis of core carbohydrates such as glucosamine necessary for tyrosinase to be active. Third, it is a method of using kojic acid or arbutin to interfere with the function of tyrosinase, an enzyme involved in melanogenesis. Fourth, using a compound having a specific toxicity to melanocytes, such as melanin-producing cells, such as hydroquinone is a method of preventing cell division of melanocytes. Fifthly, there is a method of reducing the produced melanin to decolorize.

Metabolites, such as ceramide or sphingosine-1-phosphate (S1P), commonly referred to as spingolipids, are major lipids that form the membrane structure of higher cells. Recently, many studies have been conducted as physiologically active functions such as differentiation of cells and acting as intermediate transporters of the signaling system have been revealed. In particular, as ceramide, which is present on the surface of human skin tissues and inhibits moisture divergence, is found to be functional, various types of natural or synthetic sphingolipids have begun to be used as functional compositions of cosmetics.

FTY720 (Novartis, Basel, Switzerland) was first synthesized in 1992 through a structural modification of Myriocin (ISP-1), a mycelial metabolite with immunosuppressive characteristics, from a culture of Isaria sinclarii , a cordyceps (Fujita et al. , J Antibiot, Tokyo, 47: 208-215, 1994). In particular, although FTY720 is known as a structural analog of sphingolipid, no study on melanin synthesis regulation and regulatory mechanisms has been reported.

FTY720 has already been used clinically as an inhibitor of renal immune rejection and is drawing attention as a prodrug in various fields. Although FTY720 is structurally similar to S1P, it is noteworthy that the mechanism of regulation of intracellular melanin production is different from that of S1P.

On the other hand, FTY720 has recently been reported to reduce the release of cysteinyl-leukotrienes from prostaglandin D2 and mast cells. In addition, FTY720 directly inhibits cPLA2 activity in cells, thus reducing the release of arachidonic acid and subsequently inhibiting the synthesis of prostaglandins (Payne SG., Et al., Blood, 109: 1077-85,2007). . In vivo administration of FTY720 has been shown to significantly inhibit the growth of metastatic cancer in mouse model animals with melanoma growth, and has been reported to be involved in significantly inhibiting tumor-associated angiogenesis. (LaMontagne K., et al., Cancer Res, 66 (1): 221-31, 2006).

As described above, many studies on the effectiveness of FTY720 for a wide range of cells have been conducted, but the study on the whitening action on melanocytes and its mechanisms have not been made until now.

Throughout this specification, numerous papers and patents are referenced and their citations are indicated. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.

The present inventors have studied in depth the mechanism and mechanism of whitening effect of sphingolipid and its metabolites which are excellent in whitening effect and can be used safely on human skin. As a result, it was experimentally confirmed that the FTY720 compound inhibits melanin synthesis and tyrosinase activity in melanin cells very strongly, and the whitening activity of FTY720 inhibits the expression of β-catenin and The present invention was completed by confirming that the transcription factor MITF (microphthalamia-associated transcription factor) is inhibited by expression.

 Accordingly, it is an object of the present invention to provide a whitening composition comprising FTY720 as an active ingredient.

The objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one aspect of the present invention, the present invention provides a pharmaceutical composition comprising (a) a cosmetically effective amount of FYT720 or a derivative thereof; And (b) provides a cosmetic composition for whitening comprising a cosmetically acceptable carrier.

According to another aspect of the present invention, the present invention provides a pharmaceutical composition comprising (a) a pharmaceutically effective amount of FTY720 or a derivative thereof; And (b) provides a pharmaceutical composition for the treatment or prevention of hyperpigmentation disease comprising a pharmaceutically acceptable carrier.

The present inventors have studied in depth the mechanism and mechanism of whitening effect of sphingolipid and its metabolites which are excellent in whitening effect and can be used safely on human skin. As a result, it was experimentally confirmed that the FTY720 compound inhibits melanin synthesis and tyrosinase activity in melanin cells very strongly, and the whitening activity of FTY720 inhibits the expression of β-catenin and The present invention was completed by confirming that the transcription factor MITF (microphthalamia-associated transcription factor) is inhibited by expression.

The composition of the present invention contains FTY720 or a derivative thereof as an active ingredient.

As used herein, the term "FTY720" is a compound represented by the following Chemical Formula 1, and the component name is Fingolimod, 2-amino-2- [2- (4-octylphenyl) ethyl] propane-1 A compound having an IUPAC official name of, 3-diol (2-amino-2- [2- (4-octylphenyl) ethyl] propane-1,3-diol).

[Formula 1]

As used herein, the term “derived from FTY720” is meant to include any molecule to which any chemical modification has been applied to the FTY720 molecule as long as it has the same or similar whitening effect as that of the FTY720 molecule. The FTY720 derivative is for example a phosphate ester of FTY720, or a metabolite thereof, a pharmaceutically acceptable salt or cosmetically acceptable salt of FTY720, a bioisostere of FTY720 and a cell membrane. Examples include, but are not limited to, FTY720 molecules modified with phosphate groups to facilitate permeation.

Pharmaceutically acceptable salts or cosmetically acceptable salts of FTY720 include, for example, acid addition salts to increase the solubility of FTY720, most preferably hydrochloride salt of FTY720.

The present invention is based on the finding that FTY720 significantly inhibits the synthesis of melanin and the expression of tyrosinase, and provides novel whitening efficacy of FTY720 or its derivatives.

According to a preferred embodiment of the present invention, the present invention provides a cosmetic composition for whitening FTY720 or a derivative thereof exhibits whitening activity through β-catenin expression inhibition or MITF (microphthalamia associated transcription factor) expression inhibitory action .

The whitening activity of FTY720 or its derivatives, which is an active ingredient of the present invention, is achieved by reducing the expression of β-catenin or by reducing the expression of the transcription factor MITF (microphthalamia-associated transcription factor).

According to a preferred embodiment of the present invention, the present invention provides a cosmetic composition for whitening, the content of FTY720 or derivatives thereof is in the range of 0.01 to 30.0% by weight relative to the total weight of the cosmetic composition. When the content of FTY720 or derivatives thereof is less than 0.01% by weight, it is difficult to obtain a desirable whitening effect, and when it exceeds 30.0% by weight, it is difficult to obtain an increased whitening effect according to an increased effective ingredient content and an increase in cost.

According to another preferred embodiment of the present invention, the present invention provides a cosmetic composition for whitening wherein the cosmetic composition further comprises a sunscreen or a light scattering agent. The sunscreen or light scattering agent serves to block ultraviolet rays, which are the main factors of melanin formation, and further enhances the whitening effect of the FTY720 of the present invention. A sunscreen or a light scattering agent can use a benzophenone type compound, for example.

As used herein, the term "cosmetic effective amount" means an amount sufficient to achieve the skin whitening efficacy of the above-described FTY720 of the present invention or a derivative compound thereof.

The components included in the cosmetic composition of the present invention include components conventionally used in cosmetic compositions in addition to the active ingredient, and include conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers. do.

Cosmetic compositions of the present invention may be prepared in any formulation conventionally prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing , Oils, powder foundations, emulsion foundations, wax foundations and sprays, and the like, but are not limited thereto. More specifically, it may be prepared in the form of a flexible lotion (skin), nourishing lotion (milk lotion), nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder. .

When the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components. Can be.

In the case where 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. Especially, in the case of a spray, a mixture of chlorofluorohydrocarbons, propane / Propane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, a liquid diluent such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, and microcrystals are used as carrier components. Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

When the formulation of the present invention is a surfactant-containing cleansing, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide. Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

FTY720 or derivative compounds thereof of the present invention can be used as an active ingredient of a pharmaceutical composition for the treatment or prevention of diseases caused by hyperpigmentation.

As used herein, the term "hyperpigmentation" means that the skin or nails become black or dark compared to other areas due to excessive increase of melanin in certain areas.

Preferably, the disease due to hyperpigmentation includes, but is not limited to, blemishes, freckles, senile plaques, or solar lentigines.

According to a preferred embodiment of the present invention, the therapeutic or prophylactic efficacy of the disease by hyperpigmentation of the FTY720 or a derivative compound thereof may inhibit β-catenin expression or MITF (microphthalamia associated transcription factor) expression suppression effect. Is done through.

Pharmaceutically acceptable carriers included in the pharmaceutical compositions of the present invention are those commonly used in the preparation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like It doesn't happen. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).

Suitable dosages of the pharmaceutical compositions of the invention vary depending on factors such as the formulation method, mode of administration, age, weight, sex of the patient, degree of disease symptom, food, time of administration, route of administration, rate of excretion and response to reaction. In general, the skilled practitioner can readily determine and prescribe a dosage effective for the desired treatment. Meanwhile, the dosage of the pharmaceutical composition of the present invention is preferably 0.01-2000 mg / kg body weight per day.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and when administered parenterally, may be administered by intravenous infusion, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, or the like. It is preferable that the route of administration of the pharmaceutical composition of the present invention is determined according to the type of the disease to be applied.

For example, the pharmaceutical composition of the present invention is preferably administered in a manner applied topically to the skin because it is used for the treatment of skin diseases caused by overdeposition of melanin pigment.

The pharmaceutical compositions of the present invention may be prepared in unit dosage form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or may be prepared by incorporation into a multi-dose container. The formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.

As described in detail above, the present invention relates to a whitening cosmetic composition comprising FTY720 or a derivative thereof as an active ingredient and a pharmaceutical composition for the treatment or prevention of hyperpigmentation disease. FTY720 or a derivative thereof, which is an active ingredient of the present invention, exhibits excellent whitening efficacy by inhibiting the synthesis of melanin and the expression of tyrosinase.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Example

Example 1: Cytotoxicity experiment

To determine the cytotoxicity of FTY720 (2-amino-2- [2- (4-octylphenyl) ethyl] propane-1,3-diol) (Calbiochem, San Diego, CA, USA), Mel-Ab cells The cytotoxic effect was measured by administering FTY720.

First, Mel-Ab melanocytes were treated with 5% CO ₂ , 10% fetal bovine serum (FBS), 100 nM TPA, 1 nM CT, 50 μg / mL streptomycin, and 50 μg / mL under 37 ° C. Incubated in DMEM with penicillin. Mel-Ab melanocytes cultured as described above were treated with FTY720 for 24 hours for each concentration of 0, 0.01, 0.1, 1, 5, 10 μM and then cultured again. Then, the culture medium was removed, stained with 0.5 ml of 0.1% crystal violet, and the effect on Mel-Ab melanocytes of FTY720 was measured.

The undyed crystal violet was washed several times and the crystal violet remaining in the cells was extracted using 1.0 ml of 95% ethanol. The absorbance of the extracted crystal violet was measured at 590 nm using an Enzyme Linked Immunosorbent Assay (ELISA) reader to evaluate this measurement as the degree of proliferation of the cells (Dooley et al., 1994). The measurement result is shown in FIG.

As shown in FIG. 1, FTY720 did not show toxicity to Mel-Ab melanocytes at a concentration of 0.01-5 μM, whereas 10 μM showed toxicity to Mel-Ab melanocytes.

Example 2: Inhibitory Effects of Mel-Ab Cells on Melanin Synthesis

Mel-Ab melanin cells were cultured in the same manner as described in Example 1, and FTY720 was treated for each concentration of 0, 0.01, 0.1, 1, and 5 μM, and then the degree of melanin synthesis was measured. The measurement results are shown in FIGS. 2A and 2B. As shown in the measurement results of FIGS. 2A and 2B, it showed a concentration-dependent melanin synthesis inhibitory effect that melanin synthesis was inhibited as the treatment concentration of FTY720 increased.

Example 3: Inhibition of tyrosinase activity

In this example, the inhibition of tyrosinase activity of FTY720 was measured. After culturing Mel-Ab melanocytes in the same manner as described in Example 1, and treated FTY720 for each concentration of 0, 0.01, 0.1, 1, 5 μM, tyrosine (tyrosine) as a raw material for melanin production ) Was added to the cell sample to be measured, and a method of slightly modifying the method of Koji Tomita, which calculates the amount of melanin production by calculating the amount of melanin production and calculated the inhibition rate of tyrosinase activity, was applied.

First, Mel-Ab melanocytes were plated at a density of 1 × 10 ⁵ cells / well in 96 well plates, followed by culturing, and the cultured cells were washed with PBS, and then treated with 1% Triton-X / PBS (Triton-X / PBS). ), And pulverized by repeating freezing and thawing with liquid nitrogen. Finally, after cell thawing, 10 μl of 10 mM L-DOPA was added to each well of 96 wells, mixed, and measured at 37 ° C. for 10 minutes or longer. Absorption was measured at 475 nm and experimental values normalized to mushroom tyrosinase. The measured result is shown in FIG. 2C.

As shown in Figure 2c, it was confirmed that the activity of tyrosinase decreases as the FTY720 is treated at different concentrations.

According to the results shown in Examples 2 and 3 and FIGS. 2A, 2B and 2C, it was found that the activity of tyrosinase was decreased by FTY720 treatment, and thus melanin synthesis was also reduced.

Example  4: Mel - Ab  In melanocytes GSK Activation of -3β GSK Mechanism of Melanin Synthesis by -3β Inhibitor

To determine the mechanism by which FTY720 inhibits melanin synthesis, GSK-3β was treated with cultured Mel-Ab melanocytes at 1 μM concentration of FTY720, followed by 0, 24, 48, and 72 hours. Changes in the expression and phosphorylation of (Glycogen synthase kinase-3β) and β-catenin expression were observed, respectively. The results are shown in Figure 3a.

As shown in the results of Figure 3a, after treatment with Mel-Ab melanocytes FTY720, it can be seen that after 24 to 48 hours, the inactive form of GSK-3β is converted to the phosphorylated active form. Recently, it has been reported that GSK-3β is involved in the regulation of melanocyte differentiation by cAMP and that melanin synthesis is enhanced through various GSK-3β inhibition (Khaled M., et al., J Biol Chem. 277 (37). ): 33690-97; Bellei B., et al., Cellular Signaling, 20: 1750-61).

As shown in FIG. 3A, it could be presumed that FTY720 showed a whitening effect by activating GSK-3β to reduce melanin formation in melanocytes. Experiments with inhibitors of GSK-3β were conducted to confirm this presumption. As can be seen from the results shown in FIG. 3B, inhibitors of GSK-3β [BIO, (2'Z, 3'E) -6-bromoindirubin-3'-oxime; SB216763] was treated with FTY720 resulted in no increase in melanin content. These results show that the inhibitory effect of melanin production of FTY720 is not due to the signaling pathway by activation of GSK-3β.

In conclusion, it was concluded that the inhibitory effect of melanogenesis of FTY720 was not through the activation pathway of GSK-3β but through the inhibition of β-catenin expression.

In addition, the effect of FTY720 on the expression level of the microphthalmia associated transcription factor (MITF) was measured under the same conditions as the above experiment. As shown in the results of FIG. 4, it was confirmed that there was no change in expression of MITF at the beginning of the FTY720 treatment, but the expression gradually decreased over time, and the maximum reduction was performed at 48 hours, and then recovered at 72 hours. This tendency was the same in the expression of tyrosinase, an enzyme that directly regulates melanin synthesis (see FIG. 4). FTY720 regulates melanin production by inhibiting the expression of β-catenin mRNA and inducing a decrease in the expression of MITF (see FIG. 5).

Example 5: Flexible Cosmetics Manufacturing

As a formulation of a cosmetic composition comprising FTY720, 1 wt% of FTY720, 3 wt% of glycerol, 5 wt% of ethanol, 2 wt% of propylene glycol, a small amount of fragrance, and a residual amount of purified water were prepared.

Example 6: Convergent Cosmetic Manufacturing

As a formulation of a cosmetic composition comprising FTY720, 1% by weight of FTY720, 4% by weight of beeswax, 4% by weight of liquid paraffin, 4% by weight of squalene, 3% by weight of glycerin, trace amounts of preservatives, traces of flavor, and residual purified water To prepare a convergence cosmetic water.

Example 7: Nutrition Cream

As a formulation of a cosmetic composition comprising FTY720, 0.5% by weight of FTY720, 6% by weight of propylene glycol, 4% by weight of glycerin, 5% by weight of liquid paraffin, 3% by weight of squalene, 1.5% by weight of polysorbate60, and the balance Purified water was mixed to prepare astringent cosmetic water.

Example 8: Massage cream manufacturer

As a formulation of a cosmetic composition comprising FTY720, 0.2% by weight of FTY720, 7% by weight of petrolatum, 10% by weight of liquid paraffin, 2% by weight of beeswax, 2.5% by weight of polysorbate, 3% by weight of squalene, 4% by weight of glycerin, Massage cream was prepared by mixing 6% by weight of propylene glycol, a trace amount of a preservative, and a residual amount of purified water.

Example 9: Essence manufacturer

As a formulation of a cosmetic composition comprising FTY720, 2% by weight of FTY720, 2% by weight of propylene glycol, 4% by weight of glycerine, 7% by weight of ethanol, a trace amount of preservative, a small amount of fragrance, and a residual amount of purified water are mixed. Prepared.

Example 10: Pack manufacturer

As a formulation of a cosmetic composition comprising FTY720, 1% by weight of FTY720, 6% by weight of propylene glycol, 4% by weight of glycerin, 2% by weight of beeswax, 30% by weight of liquid paraffin, trace amounts of preservatives, traces of flavor, and The remaining amount of purified water was mixed to prepare a pack.

Having described the specific part of the present invention in detail, it is apparent to those skilled in the art that the specific technology is merely a preferred embodiment, and the scope of the present invention is not limited thereto. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

1 is a graph showing the results of measuring the toxicity of Mel-Ab melanin cells according to the concentration of FTY720, the active ingredient of the cosmetic composition for whitening of the present invention.

Figure 2a is a photograph of a microscopic observation of Mel-Ab melanocytes treated for each concentration of administration of FTY720, the active ingredient of the cosmetic composition for whitening of the present invention. As the concentration of FTY720 increases, it can be seen that melanin formation is suppressed.

Figure 2b is a graph showing the effect of inhibiting melanin synthesis in Mel-Ab melanocytes according to the treatment concentration of FTY720.

Figure 2c is a graph showing the concentration-dependent inhibitory effect of tyrosinase in Mel-Ab melanin cells according to the concentration of FTY720 treatment.

Figure 3a is a photograph of the changes in activity and β-catenin (catenin) expression of GSK-3β according to the treatment time of FTY720, the active ingredient of the cosmetic composition for whitening of the present invention.

3b is an active inhibitor of GSK-3β as an active ingredient of the cosmetic composition for whitening of the present invention [BIO, (2'Z, 3'E) -6-bromoindirubin-3'-oxime; SB216763] is a graph showing the results of measuring the synthesis of melanin in Mel-Ab melanocytes when treated with.

FIG. 4 is a diagram showing the expression of MITF (microphthalmia associated transcription factor) and tyrosinase expression according to the treatment time of FTY720, the active ingredient of the whitening cosmetic composition of the present invention, in Mel-Ab melanin cells. .

Figure 5 shows the change in the expression of β-catenin, MITF, tyrosinase mRNA expression according to the treatment time of FTY720, the active ingredient of the whitening cosmetic composition of the present invention in Mel-Ab melanin cells to be.

Claims (9)

(a) a cosmetically effective amount of a compound represented by the following formula (1) or a cosmetically acceptable salt thereof; And (b) a cosmetically acceptable carrier. [Formula 1]

The cosmetic composition for whitening according to claim 1, wherein the content of the compound of Formula 1 or a cosmetically acceptable salt thereof is in a range of 0.01 to 30.0 wt% based on the total weight of the cosmetic composition. delete The cosmetic composition of claim 1, wherein the cosmetic composition further comprises a sunscreen or a light scattering agent. The method of claim 1 wherein the cosmetic composition is a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray Whitening cosmetic composition, characterized in that the formulation is selected from the group consisting of. The method of claim 1, wherein the compound of Formula 1 or a cosmetically acceptable salt thereof exhibits whitening activity through β-catenin expression inhibition or MITF (Microphthalamia-associated transcription factor) expression inhibition action Whitening cosmetic composition. (a) a pharmaceutically effective amount of a compound of formula (1) or a pharmaceutically acceptable salt thereof; And (b) a pharmaceutical composition for the treatment or prophylaxis of hyperpigmentation disease comprising a pharmaceutically acceptable carrier. [Formula 1]

8. The pharmaceutical composition according to claim 7, wherein the hyperpigmentation disease is blemish, freckles, senile plaques, or solar lentigines. delete

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