KR20010103057A - Composition of miconazole for external application and skin-whitening - Google Patents

Abstract

The present invention relates to an external preparation composition for mycosol-containing skin whitening, and has a novel whitening use of myconazole, which inhibits the activity of tyrosinase, the main enzyme of melanin pigment production, and inhibits the production of melanin pigment, as an active ingredient. By adding 5.00% by weight, it is excellent in stability, has no side effects, and has an effect of inhibiting melanin pigment formation, thereby providing an external composition for skin whitening having an excellent skin whitening effect that prevents pigmentation of the skin such as blemishes, freckles and sunburn. .

Description

Composition for external application for skin whitening containing myconazole {Composition of miconazole for external application and skin-whitening}

The present invention relates to an external preparation composition for myconazole-containing skin whitening. More specifically, the present invention is an external preparation for skin whitening that inhibits melanin production and has excellent skin whitening effect by containing the active ingredient tyrosinase, the main enzyme of melanin pigment production, and myconazole, which inhibits its production, as an active ingredient. It relates to a composition.

Human skin color is genetically determined by the concentration and distribution of melanin in skin cells, but also by environmental or physiological conditions such as exposure to sun UV rays, the use of female hormones, pregnancy, cosmetics, fatigue, and stress. Under the influence, melanin pigment may be deposited on the skin, which may lead to blackening of the skin. Among them, exposure to ultraviolet rays, the use of female hormones, and pregnancy account for 60 to 70%, which is more likely to occur in women. Due to these causes, pigment diseases such as blemishes, freckles, etc. occurring on the face have emerged as a major problem in women's beauty.

The mechanism of skin blackening is as follows. An internal and external factor activates an enzyme called tyrosinase, which acts on tyrosine, a type of amino acid present in skin tissue, producing dopa and then dopaquinone. Through the non-enzymatic automatic oxidation process, melanin is synthesized from melanoma in melanoctyte, a skin pigment cell, and melanin is synthesized into keratinocyte, which is a keratinocyte through the melanosome. It is delivered to the skin surface by the keratinization process to protect the skin from ultraviolet rays. Therefore, melanin is an indispensable defense in our body, and also plays an important role as an effective free radical scavenger to remove various radicals that modify biological components such as proteins, lipids, nucleic acids, etc. If the physiological function of the skin lesions and aging is reduced, it will be deposited on the skin surface, causing spots, blotch, freckles and various pigmentation.

As the causes and mechanisms of skin blackening have been revealed, melanin may be incorporated into cosmetics or medicines with substances that have an effect of inhibiting the activity of tyrosinase, an enzyme involved in skin blackening, or by inhibiting some reactions during the production of melanin. In order to reduce the production of the skin to improve skin whitening, blemishes, freckles and the like are commonly used. Representative materials used for this purpose are tocopherol, vitamins, ascorbic acid (ascorbic acid), kojic acid (hydrojone) and the like (hydroquinone). However, ascorbic acid has a low inhibitory effect on tyrosinase activity and low molecular stability, and thus it is not suitable as an inhibitor of melanin production, while kojic acid has a strong inhibitory effect on tyrosinase activity. It has a problem of stability such as lowering of the titration and also has a limitation in use because it has high skin irritation and denatures melanin pigment or melanocytes. Hydroquinone is recognized as effective but has sensitization to skin. Use is generally limited due to safety concerns. In particular, the biggest problem of existing melanogenesis inhibitors is that in clinical trials on real human skin, the spots may remain partially without being completely lost, may cause side effects, and excessive time to achieve the desired purpose, e.g. For example, it is not a desirable treatment because it requires more than 6 months assuming continuous use. Meanwhile, peeling or laser treatment may be used as a method of removing epidermal spots of less than 0.1 mm in depth. These methods may also cause physical side effects and rather deterioration of the spots during the procedure.

Accordingly, the present inventors have been studying the substance that has a skin whitening effect that can have a visible effect in a short period of time without side effects in removing the blemish on the skin completely, melanin production of miconazole, a kind of imidazole derivatives Tests of inhibitory and tyrosinase inhibition showed that myconazole has excellent melanin inhibitory activity and tyrosinase inhibitory activity. It is said to be a substance for use.

As for the report on myconazole, Patent No. 96-03321, an antifungal agent, is a superficial ringworm fungi (coccus tinea), mechanical insects (coccus tinea), and paint swelling (coccus ringworm) The use of the imidazole derivatives econazole and myconazole has been reported as a therapeutic agent for skin diseases caused by and Candida. In addition, Patent No. 89-00207 has registered a patent as a skin protection composition that can prevent or treat acute inflammatory skin diseases. However, there is no known application of myconazole to melanin production, in particular, as a whitening agent.

Accordingly, it is an object of the present invention to provide a novel whitening agent for myconazole having melanin production inhibitory activity and tyrosinase activity inhibitory action.

Another object of the present invention is to provide an external preparation composition for mycosol-containing skin whitening having a skin whitening effect by containing the above myconazole as an active ingredient.

The above object of the present invention is to determine the appropriate concentration of myconazole treatment by treating myconazole to B16 melanomer cell line and measuring the survival rate of cells, and by using it to inhibit the tyrosinase activity of myconazole, alpha-melanosite promoting hormone and The whitening effect of myconazole of the present invention was investigated by investigating the effects on the inhibition of tyrosinase activity, melanin production and tyrosinase protein expression in hyperpigmentation with the increase of cAMP (adenosine monophosphate) by treatment with fosporin. It was achieved by confirming the melanin production inhibitory effect.

Hereinafter, the configuration of the present invention will be described in detail.

1 is a result of measuring the cell viability of the B16 melanomer cell line when the present invention myconazole is treated at a concentration of 0.1 μg / mL to 50.0 μg / mL.

Figure 2 shows the results of measuring tyrosinase activity in the B16 melanomer cell line when the present invention myconazole was treated at a concentration of 0.1 μg / mL to 10.0 μg / mL.

Figure 3 shows tyrosinase during hyperpigmentation by alpha-melanosite promoting hormone (α-MSH) in B16 melanomer cell line when the present invention myconazole was treated at a concentration of 0.1 μg / mL to 10.0 μg / mL. It is a result of measuring activity.

Figure 4 shows the results of measuring the tyrosinase activity during hyperpigmentation by phosphorin in the B16 melanomer cell line when the present invention myconazole was treated at a concentration of 0.1 μg / mL to 10.0 μg / mL.

5 is a comparative experiment result of the present invention myconazole and hydroquinone to inhibit tyrosinase activity.

6 shows the results of measurement of the amount of melanin biosynthesis in the B16 melanomer cell line when the present invention myconazole was treated at a concentration of 0.1 μg / mL to 10.0 μg / mL.

Figure 7 is the result of measuring the tyrosinase protein expression in the B16 melanomer cell line by Western blotting when the present invention myconazole is treated at a concentration of 0.1 μg / mL to 10.0 μg / mL.

The present invention comprises the steps of dissolving myconazole in dimethylsulfoxide (DMSO) and diluting while adjusting the concentration to prepare a miconazole sample; Selecting a cell-derived B16 melanomer cell line as an experimental cell line and culturing it; Treating the cultured B16 melanomer cell line with a concentration of 0.1 μg / mL to 50 μg / mL, and then examining the survival rate of the cells by sulforhodamine B quantification to determine the concentration of the miconazole; Identifying the effect of myconazole that inhibits the activity of a tyrosinase enzyme that promotes melanin synthesis; Inhibition of tyrosinase by miconazole when hyperpigmentation is induced by alpha-melanosite promoting hormone (α-MSH), which increases melanin biosynthesis by increasing the concentration of cAMP and altering the mechanisms involved in signaling Identifying the effect; Confirming the tyrosinase inhibitory effect of myconazole when treatment with forskolin induced hyperpigmentation by increasing intracellular cAMP concentration; Comparing the hydroquinone known as a conventional whitening agent with the inhibitory activity of tyrosinase activity of myconazole of the present invention; Identifying the effect of myconazole that inhibits melanogenesis; Performing a Western blotting method using a tyrosinase antibody to determine the effect of myconazole on tyrosinase protein expression; Preparing an external cream for skin whitening containing myconazole to test stability and skin pigmentation inhibitory effect; Preparing an external ointment for skin whitening of the present invention by mixing a proper amount of myconazole, light lead, diethyl sebagate, squalane, propylene glycol, sodium benzoate and petrolatum, and confirming that the skin whitening effect on the blemishes; Constituting the composition of the external preparation liquid preparation, milk lotion and pack agent for skin whitening of the present invention containing myconazole.

The blending amount of myconazole in this step is 0.05-5.00% by weight, preferably 0.1-2.0% by weight relative to the total weight of the external preparation composition. If it is less than 0.05% by weight, the whitening effect of the present invention is not sufficiently exhibited. If it exceeds 5.0% by weight, there is a problem in skin safety, which is not preferable. Therefore, the content of the whitening agent can be maximized at 2.0% by weight or more, it is most appropriate to contain 0.1-2.0% by weight.

The external preparation for skin whitening of the present invention includes ingredients used in external preparations of skin, such as cosmetics and medicines, in addition to the essential ingredients of the above steps, for example, other whitening agents, moisturizing agents, antioxidants, oily ingredients, ultraviolet absorbers, surfactants, thickeners, alcohols. And the like, powder components, colorants, flavors, aqueous components, water, various skin nutrients and the like can be appropriately blended as necessary.

The method of applying the present invention to the external preparation for skin whitening at the above step is provided with creams, ointments, solutions, lotions, packs and the like, but the present invention is not limited thereto. All are formulated.

Hereinafter, the specific method of the present invention will be described in detail with reference to Examples and Test Examples, but the scope of the present invention is not limited to these Examples and Test Examples, but the test method used in the following Examples and Test Examples. And unless otherwise indicated, according to the following reference examples.

Reference Example 1 Preparation of Myconazole Sample

In order to prepare a sample of the present myconazole, myconazole (Sigma, USA) was dissolved in dimethyl sulfoxide (DMSO), the solution was diluted to adjust the concentration, and the following experiment was performed using the same. .

Reference Example 2: Culture of B16 Melanomeric Cell Line

B16 mouse melanoma cells derived from the mouse were used by the Korea Cell Line Bank. Cultivation was performed using a DMEM medium containing 10% Petal bovine serum (product of Haas) in a carbon dioxide incubator (37 ° C., 5%) and incubating 10 ⁵ cells per culture vessel and incubating for one day. After 24 hours of incubation, the miconazole sample solution was added to a concentration of 0.1-10 ㎍ / mL, and the culture was continued for 3 days, followed by quantification of sulforhodamine B, inhibitory effect of tyrosinase activity, quantification of melanin, and protein expression. Etc. were measured.

Reference Example 3 Determination of Sulphodamine B

Sulphorhodamine B (Sigma) quantitation is a test method to determine the effect of myconazole on the cell viability of B16 melanomer cells, 200μl adjusted to 1 × 10 ⁴ cells in each well After dispensing into 96 well plates and incubating for 24 hours, the appropriate concentration of myconazole was treated and incubated for 48 hours. The control group and the experimental groups were measured as follows with three wells each. After culturing, the cells were fixed with 50% trichloroacetic acid at 4 ° C. for 1 hour, stained with 0.4% sulfodadamine B / 1% acetic acid, washed four times with 1% acetic acid, and dried. After dissolving the protein stain bound with a 10 mM Tris base, the absorbance was measured at 540 nm with a spectrophotometer.

Reference Example 4 Tyrosinase Activity Inhibition Test

Inhibition of tyrosinase activity against myconazole was measured. Harvest the melanocytes to make cell precipitates, add 100 μl cell lysate (1% Triton X-100, 10 mM sodium phosphate, pH 7.0, 0.1 mM PMSF) and destroy the cells by shaking occasionally at 4 ° C for 30 minutes. The supernatant was collected by centrifugation and used as a tyrosinase activity measurement solution. 100 μl of 100 mM sodium phosphate (pH 7.0) was added to 50 μl supernatant, and kept warm in a water bath at 30 ° C. for 5 minutes. Then, 50 μl of 100 mM L-dopa was added and the absorbance was measured at 37 ° C. and 405 nm with a thermostat. The change was observed for 1 hour. In this case, using the buffer instead of myconazole as a control, the absorbance was measured by the same method to calculate the tyrosinase activity inhibition rate.

The formula for inhibiting tyrosinase activity is as follows.

Tyrosinase activity inhibition rate (%) = 100- (absorbance of each sample / reaction absorbance of control) × 100

Example 1 Effect of Myconazole on Cell Viability of B16 Melanomeric Cells

To determine the treatment concentration of myconazole, the effect of myconazole on the survival rate of B16 melanomer cells was investigated.

The prepared myconazole samples were treated with B16 melanomer cells at various concentrations from 0.1 μg / mL to 50 μg / mL, and the survival rates of the cells were observed. As a result of using the sulforhodamine B assay, which measures the amount of protein in the cell and examines the extent of cell proliferation, there was no change in cell proliferation compared to the control until the concentration of myconazole was 20 µg / mL. At higher concentrations, however, myconazole inhibited cell proliferation, reducing cell viability to 45% of the control at 50 µg / mL. The results are shown in FIG.

Example 2: Tyrosinase activity inhibition test by myconazole

First step. Inhibition of Tyrosinase Activity by Myconazole

In order to investigate the effect of myconazole on melanin synthesis, the activity inhibitory activity of tyrosinase, the most important enzyme in melanin synthesis, was measured according to the method of Reference Example 4. After 48 hours of treatment with myconazole from 0.1 µg / mL to 10 µg / mL, the inhibitory activity of tyrosinase activity was found to be 86% in the 0.1 µg / mL group treated with myconazole, 75% at 1 µg / mL, 67% at 5 μg / mL and 4.6% at 10 μg / mL. Therefore, it can be seen that myconazole significantly inhibited the activity of tyrosinase with increasing concentration (FIG. 2).

Second step. Inhibition of Tyrosinase Activity of Myconazole on Hyperpigmentation by α-MSH (alpha-melanosite Promoting Hormone)

To investigate the inhibitory effect of myconazole on the hyperpigmentation of pigment cells by external environment such as ultraviolet light, the effect of myconazole is induced when hyperpigmentation is induced by alpha-melanosite promoting hormone (α-MSH). Observed. Alpha-melanosite promoting hormone increases melanin biosynthesis by increasing the concentration of cAMP in the cell and altering the mechanisms involved in signaling. Thus, the effect of myconazole was observed when hyperpigmentation was induced with alpha-melanosite promoting hormone.

Inhibition of tyrosinase activity of B16 melanomer cells was measured after treatment with myconazole from 0.1 μg / mL to 10 μg / mL after 30 min treatment with 10 nM of alpha-melanosite promoter. The alpha-melanosite-promoting hormone-treated group showed about 2.3-fold increase in tyrosinase activity compared to the control group. The co-treated group of alpha-melanosite-stimulating hormone and myconazole 1µg / mL decreased to 64%, 21% at 5µg / mL and 3.7% at 10µg / mL compared to alpha-melanosite promoting hormone alone. . As a result, it was found that myconazole has a clear effect of inhibiting tyrosinase activity during hyperpigmentation by alpha-melanosite promoting hormone (FIG. 3).

Third step. Determination of Tyrosinase Activity Inhibition of Myconazole During Hyperpigmentation by Treatment of Forskolin

Alpha-melanosite promoters bind to specific receptors present on the surface of melanocytes, and it is known that melanin biosynthesis is increased by the combination of alpha-melanosite promoters and their receptors to increase intracellular cAMP. Therefore, the effect of myconazole was observed in hyperpigmentation by increasing cAMP by increasing intracellular cAMP concentration by activating adenylate cyclase by treating with posporin.

The tyrosinase activity of B16 melanomer cells was measured after treatment with myconazole from 0.1 μg / mL to 10 μg / mL and 30 min after 20 nM fosporin. The posporin-treated group increased tyrosinase activity about 6-fold compared to the control group. Posporin and myconazole 0.1μg / mL co-treated group was 88.6%, 64.8% at 1μg / mL, 15.9% at 5μg / mL, and 1.5% at 10μg / mL compared to POSCOline alone. It was significantly reduced compared to the treatment group. As a result, it was found that myconazole significantly inhibited tyrosinase activity during the production of hyperpigmentation by POSCORIN (FIG. 4).

Fourth step. Comparative Test of Tyrosinase Activity Inhibition of Myconazole and Hydroquinone

The B-16 melanoma cells cultured in the same manner as in Reference Example 2 were measured for tyrosinase activity inhibition ability according to each myconazole concentration and hydroquinone, and the results are shown in FIG. 5. Myconazole was found to have a very strong inhibitory effect on tyrosinase activity against cultured mouse melanoma cells. In particular, each sample was found to have a very strong inhibitory effect on tyrosinase activity at the cellular level when compared with hydroquinone, a known whitening substance.

Example 3 Effect of Myconazole on Inhibition of Melanin Production

The effect of myconazole on the amount of melanin synthesis, the final product of melanin biosynthesis, was investigated.

The B16 melanomer culture cells of Reference Example 2 were washed twice with PBS, harvested by centrifugation, and suspended in 1 ml of distilled water in the cell precipitate, pulverized by ultrasonication, and centrifuged to obtain a precipitate. In order to obtain an acid-insoluble substance, 300 µl of 1N sodium hydroxide added with 2x DMSO was added and dissolved at 80 ° C. for 1 hour. Absorbance was measured at 475 nm and melanin quantitation was determined from a standard curve prepared using synthetic melanin (Sigma) as a control. The formula for inhibiting melanogenesis is as follows.

Melanin production inhibition rate (%) = 100- (absorbance of each sample / absorbance of the control group) × 100

After treating meconazole from 0.1 μg / mL to 10 μg / mL and measuring melanin after 72 hours, it was 93% in the 0.1 μg / mL treatment group, 90% at 1 μg / mL, and 5 μg / mL at 1 μg / mL. 77%, decreased to 51% at 10 μg / mL. Therefore, it was found that myconazole inhibited the synthesis of melanin pigment (FIG. 6).

Example 4 Effect of Myconazole on Protein Expression Pattern

In order to investigate the effect of myconazole on tyrosinase protein expression, intracellular tyrosinase protein expression was investigated by Western blotting using tyrosinase antibody.

B16 melanomer cells treated with 1 μg / mL, 5 μg / mL and 10 μg / mL of myconazole (5 × 10 ⁶ ) and untreated control B16 melanomer cells were washed with PBS and cells at 4 ° C. for 30 minutes. After lysis with cell lysis buffer, the cells were centrifuged at 20,000 × g for 30 minutes. The supernatant obtained by centrifugation was concentrated using a Amicon system and quantified by Bradford assay again, and the protein (50 µg) was electrophoresed on 10% SDS-PAGE to separate proteins. . The isolated protein was transferred to nitrocellulose membrane and then incubated in blocking buffer (5% skim milk, Scheme milk) for 2 hours at room temperature. The tyrosinase antibody (Santa Cruz Co., Ltd.) was diluted 1: 500, reacted for 1 hour, washed three times with a washing solution, and diluted with a secondary peroxidase-coupled anti mouse antibody (Sigma). Reacted tyrosinase protein was confirmed by ECL system. The results are shown in FIG.

It can be seen that the myconazole treatment group significantly reduced the tyrosinase activity compared to the untreated control group, and the decrease in activity was noticeable as the treatment concentration was increased. It can be seen that myconazole not only inhibits tyrosinase enzyme activity in the cell but also inhibits the expression of the enzyme.

In summary, it was confirmed that myconazole has an excellent pigmentation inhibitory effect on the basis of tyrosinase inhibitory activity and melanin production inhibition.

Hereinafter, as an active ingredient for skin whitening containing the present invention myconazole with excellent tyrosinase inhibitory effect and melanin production inhibitory effect as an active ingredient, the cream agent and the myconazole of Preparation Example 1 and Comparative Preparation Example 1 After the preparation of the cream preparation of Comparative Preparation Example 2 containing no, the stability test and the ability to inhibit skin pigmentation were tested.

Preparation Example 1 Preparation of Cream Containing Myconazole

The formulation of the cream in the external preparation for skin whitening containing myconazole was prepared as shown in Table 1 below.

Composition of external cream for skin whitening Compounding ingredient Preparation Example 1 Comparative Production Example 1 Comparative Production Example 2 Myconazole 1.0 1.0 - Ascorbic acid - - 1.0 Sodium bisulfite 0.1 - 0.1 Cetanol 1.0 1.0 1.0 Stearic acid 15.0 15.0 15.0 Potassium hydroxide 0.7 0.7 0.7 glycerin 5.0 5.0 5.0 Propylene glycol 3.0 3.0 3.0 antiseptic a very small amount a very small amount a very small amount incense a very small amount a very small amount a very small amount Purified water to 100 to 100 to 100 [Note] Unit: weight

Example 5 stability test of the external preparation composition for skin whitening of the present invention

In order to determine the stability of the external preparation composition for skin whitening of the present invention, a safety test was performed as follows.

Cream of Comparative Preparation Example 1 was prepared in a composition in which sodium hydrogen sulfite was excluded from the composition of Preparation Example 1 of Table 1. The cream test wool of Preparation Example 1 and Comparative Preparation Example 2 was put in a transparent glass container and capped, and the degree of discoloration was observed at 1, 2, 4 and 6 weeks while standing at room temperature. The results are shown in Table 2.

Stability test results of the external preparation composition for skin whitening of the present invention Test substance 1 day 2 weeks 4 Weeks 6 Weeks Preparation Example 1 Light white Light white Light white Light white Comparative Production Example 1 Light white Brown Dark brown Maroon

As shown in the results of Table 2, the test substance containing myconazole did not discolor much after 6 weeks of storage at room temperature.

Example 6 skin pigmentation inhibition effect of the external preparation composition for skin whitening of the present invention

Twenty healthy men and women were selected to attach aluminum foil in two rows of six holes with a diameter of 7 mm in the lower part of both arms, and 60m / cm ₂ light was irradiated using ORIEL solar simulator 1000W at a distance of 10 cm from the arm. . At this time, the irradiation site was washed with 70% ethanol aqueous solution before irradiation. A pair of samples containing myconazole prepared according to Preparation Example 1 and Comparative Preparation Example 2 of Table 1 and a base not containing myconazole in ascorbic acid, twice a day from 3 days before irradiation to 3 weeks after irradiation. It was applied to the same line. For each, the degree of pigmentation in the production example and the comparative production example was visually determined, and the degree of pigmentation inhibition in the production example and the comparative production example was evaluated in three stages of remarkable effects, slight effects, and no effects. Is shown in Table 3.

Inhibition effect of skin pigmentation of the external preparation composition for skin whitening of the present invention Experimental substance A noticeable effect Slight effect no effect Preparation Example 1 8 9 3 Comparative Production Example 2 0 4 16

As shown in the results of Table 3, the external preparation composition for skin whitening containing miconazole prepared according to Preparation Example 1 showed a whitening effect for 17 out of 20 subjects, and produced ascorbic acid containing comparative Compared with the pharmaceutical composition of Example 2 showed excellent whitening efficacy, and no side effects in the skin was found that myconazole is a safe and effective blemish or freckles improvement or skin whitening agent.

Hereinafter, based on the above embodiments, by presenting a composition for applying the external preparation for skin whitening of various formulations that can provide a skin lightening effect by containing myconazole. However, the composition of the present invention is not limited to the following preparation examples.

Preparation Example 2 Composition of External Ointment for Skin Whitening

Composition of external ointment for skin whitening of the present invention Compounding ingredient Content (% by weight) Myconazole 1.5 Prepayment 5.0 Diethylsebagate 8.0 Squalane 5.0 Propylene glycol 5.0 Sodium benzoate Quantity Vaseline 75 Total 100

Example 7 Whitening Effect of the Skin Ointment for Invention of the Present Invention against Blemishes

Regardless of age and gender, 30 people with blemishes were applied to the affected area for 60 days for skin whitening, according to the composition ratio of Table 4, twice a day, and then every 10 days. The state was observed. The results are shown in Table 5.

Decontamination effect of the external preparation for skin whitening of the present invention on the blemish case Very useful utility Slightly useful Availability (%) 30 8 14 6 93.3

As shown in the results of Table 5 above, the usefulness is the result of a combination of very useful, useful, and slightly useful. Therefore, the external preparation for skin whitening of the present invention is very excellent in the removal of blemishes, that is, the whitening effect.

Preparation Example 3: External preparation liquid preparation for skin whitening of the present invention

Composition of external preparation liquid for skin whitening Ingredient Content (% by weight) Myconazole 1.5 ethanol 75 Purified water to 100

Preparation Example 4: The external preparation mill lotion for skin whitening of the present invention

The present invention external preparation milk lotion composition for skin whitening Ingredient Content (% by weight) Myconazole 0.5 Propylene glycol 5.4 glycerin 4.0 Triethanolamine 1.2 Tocopheryl Acetate 3.0 Liquid paraffin 5.0 Squalane 3.0 Macadamia Nut Oil 2.0 Polysorbate 60 1.5 Sorbitan sesquioleate 1.0 Carboxy Vinyl Polymer 1.0 Incense, preservative a very small amount Purified water to 100

Preparation Example 5: External preparation pack for skin whitening of the present invention

Invention pack composition for skin whitening Compounding ingredient Content (% by weight) Myconazole 0.5 Polyvinyl alcohol 15.0 glycerin 5.0 Propylene glycol 4.0 ethanol 8.0 Polyoxyethylene oleylethyl 1.0 Methyl paraoxybenzoate 0.2 Pigment Quantity incense Quantity Purified water to 100

As described in the above Examples and Preparation Examples, the present invention provides a novel use of myconazole as a whitening agent, which is known as an antifungal agent, to inhibit tyrosinase activity, melanogenesis, and tyrosinase protein expression of myconazole. As a result of measuring the effect on the skin, the effect of whitening and melanin production was proven using myconazole, which has excellent stability, no side effect, and whitening effect that can provide a whitening effect for skin whitening and other external preparations. Therefore, it is a very useful invention in the cosmetic and pharmaceutical manufacturing industry.

Claims (4)

An external preparation composition for skin whitening comprising 0.05 to 5.00% by weight of myconazole as an active ingredient based on the total weight of the composition. The external preparation composition for skin whitening according to claim 1, wherein the content of the myconazole is 0.01 to 2.00% by weight. An external preparation for skin whitening, comprising an external preparation composition for skin whitening containing the miconazole according to claim 1 as an active ingredient. The external preparation for skin whitening according to claim 3, wherein the external preparation for skin whitening has an external skin cream, ointment, liquid, lotion or pack formulation.