KR20040060157A - Cosmetic Composition for Skin-Whitening Comprising Tranexamic Acid as Active Ingredient - Google Patents

Abstract

PURPOSE: Provided is a skin whitening cosmetic composition containing tranexamic acid as an active ingredient to inhibit the growth of melanocytes and give skin whitening effect. Therefore, it effectively inhibits the synthesis of melanin, and has safety to the skin and stability. CONSTITUTION: A skin whitening cosmetic composition is characterized by containing, based on the total weight of the composition, 0.0001-10.0 wt.% of tranexamic acid as an active ingredient. It is formulated into liquid, suspension, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, foundation and spray.

Description

Cosmetic composition for skin whitening containing tranexamic acid {Cosmetic Composition for Skin-Whitening Comprising Tranexamic Acid as Active Ingredient}

The present invention relates to a cosmetic composition, and more particularly, the present invention relates to a cosmetic composition for skin whitening comprising tranexamic acid.

Pigments that determine human skin color include melanin, hemoglobin, carotenoids, and the like, and various colors of skin, hair, and eyes are determined by these pigments. The most important pigment that determines the color of the skin is melanin, which is determined by a series of melanin biosynthetic processes that are genetically strictly planned and regulated. However, when melanin is synthesized and accumulated excessively due to environmental factors such as ultraviolet rays or chemicals or physiological factors such as stress and fatigue, it causes blemishes and freckles.

Melanin pigment is produced in melanocytes, which is a phenolic polymer material having a complex form of black pigment and protein, and plays an important role in inhibiting skin damage caused by ultraviolet rays from the sun.

Melanin is produced by the action of an enzyme called tyrosinase present in pigmented cells. Tyrosinase is found exclusively in melanocytes, which are pigment cells. Melanosite is located in the basal layer and hair root of the epidermis. Melanin pigments are produced and deposited in melanosite-specific organs called melanosomes, which are then transported from melanocytes to surrounding keratinocytes and spread widely through the skin epidermis or pores.

Several other enzymes are known that are involved in melanin biosynthesis, such as tyrosinase related protein 1 (TRP 1) and tyrosinase related protein 2 (TRP 2) (Cohen, T., et al. Nucleic Acids Res. 18: 2807-2808 (1990)); Jackson, IJ, et al., EMBO J., 11: 327-535 (1992)). The detailed function of these TRPs is unknown, but recent studies have shown that tyrosinase, TRP 1 and TRP 2 interact in in vivo to form complexes, and the activity of tyrosinase in these complexes is reduced, thus TRPs are believed to act as inhibitors of tyrosinase activity (Orlow, SJ, et al., J. Invest. Dermatol. , 103: 196-201 (1994)).

Melanin is converted to dopa (DOPA) and dopaquinone from tyrosine, which is a type of amino acid by tyrosinase, TRP 1 and TRP 2, and then biosynthesized through non-enzymatic oxidation. The produced melanin is transferred to keratinocytes through melanosomes, and the keratinocytes are released to the skin surface after 28 days of keratinization. However, in the keratinization process, the melanin is excessively produced by some factor, and the pigmentation occurs if the melanin pigment is not completely removed by the keratinization.

On the other hand, the action of the whitening agent used in the whitening cosmetics appears in various ways. First, as a method of removing the cause of melanin by blocking ultraviolet rays, this method uses a light scattering agent or a light blocking agent. Second, as a method of inhibiting the biosynthesis of tyrosinase, this method uses a substance that blocks signal transduction or inhibits gene expression. Third, as a method of inhibiting the function of tyrosinase, this method uses a substance which competitively binds to the substrate of the enzyme or a substance which loses the activity of the enzyme by binding to the enzyme and changing its structure. Fourth, it is a method of using a substance having a specific toxicity to melanocytes.

On the other hand, there are a variety of materials used as a conventional skin lightening agent.

The most known to inhibit tyrosinase, an important enzyme of melanin synthesis, is chelators such as kojic acid, and substrate-like substances such as arbutin. In addition, plant extracts include lettuce extract, licorice extract and the like. However, these whitening raw materials have the disadvantage that the effect does not last long because of low stability, so the application range of the product is very narrow.

In addition, L-ascorbic acid is a substance that inhibits tyrosinase activity by reducing quinones to phenols. Although L-ascorbic acid shows a high inhibitory effect on tyrosinase activity, it tends to be unstable in the formulation, so it is easily oxidized by heat, air, and moisture. It causes irritation to the skin, the stability of the whitening cosmetics product including this is not good, the use thereof is limited, and the effect also has a drawback that significantly drops over time. Various kinds of L-ascorbic acid derivatives have been synthesized for stabilization of L-ascorbic acid, but they are not only difficult to absorb into the skin, but they are not easily converted to L-ascorbic acid even when absorbed into the skin. There is this.

In addition, hydroquinone has a side effect of causing whitening or vitiligo, which partially whitens the skin, because it completely eliminates the melanin production function that regulates skin protection.

Throughout this specification, a number of articles are referenced and their citations are indicated. The disclosures of cited articles are incorporated herein by reference in their entirety to more clearly describe the level of the technical field to which the present invention pertains and the content of the present invention.

The present inventors have made intensive efforts to improve the problems appearing in the conventional whitening agent, the composition containing the tranexamic acid is very excellent in inhibiting the proliferation of melanocytes, while the cosmetic composition comprising the same shows an excellent whitening effect The present invention was completed by discovering excellent formulation stability and skin safety.

Therefore, the object of the present invention is for skin whitening Cosmetics Composition Provided place have.

Other objects and advantages of the invention will be apparent from the following examples and claims.

According to one aspect of the present invention, the present invention provides a cosmetic composition for skin whitening comprising tranexamic acid as an active ingredient.

According to another aspect of the present invention, the present invention provides a composition for inhibiting melanocyte proliferation comprising tranexamic acid as an active ingredient.

The present inventors screened various materials in an effort to overcome the problems in the conventional whitening agent and to develop a material having an excellent whitening effect. As a result, the composition containing tranexamic acid has an effect of inhibiting the growth of melanocytes. It was found to be very good and the cosmetic composition comprising the same exhibits excellent whitening effect and also excellent formulation stability and skin safety.

Tranexamic acid is a trans-4- (aminomethyl) cyclohexanecarboxylic acid and has a molecular formula of C ₈ H ₁₅ NO ₂ . The tranexamic acid is known to have an antifibrinolytic effect and is used as a hemostatic agent or a thrombolytic agent.

In the present invention, it was confirmed that the tranexamic acid exhibits a whitening effect by inhibiting the proliferation of melanocytes, which are skin pigment cells, and inhibiting melanin production. The melanocyte proliferation inhibitory effect of such tranexamic acid increases in a concentration dependent manner of the tranexamic acid.

According to a preferred embodiment of the present invention, the content of the tranexamic acid in the cosmetic composition of the present invention is 0.0001-10.0% by weight relative to the total weight of the cosmetic composition, when the content is less than 0.0001% by weight melanocyte growth inhibitory effect If weak and the content exceeds 10.0% by weight, skin irritation may be caused. More preferably, the content of the tranexamic acid is 0.01-2.0% by weight relative to the total weight of the cosmetic composition.

The components included in the cosmetic composition of the present invention include components conventionally used in cosmetic compositions in addition to tranexamic acid as an active ingredient, and include, for example, conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and perfumes, And carriers.

The whitening composition 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 It may be formulated as cleansing, oil, powder foundation, emulsion foundation, wax foundation, spray, and the like, but is not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, astringent lotion, nutrition lotion, nutrition 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.

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, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane 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, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals 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, a methyltaurate, a sarcosinate, a 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.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, it is to those skilled in the art that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention. Will be self-evident.

Example

Example material

The tranexamic acid of the present invention was purchased from Asahi Kasei (Japan) and used (purity: 99.9%).

Example 1: Experiment of proliferative effect on fibroblasts, keratinocytes and melanocytes

Human normal fibroblasts, human normal keratinocytes and human normal melanocytes were inoculated to ¹ × 10 ⁴ cells in each well of a 96-well microplate, respectively, and incubated in DMEM medium for 24 hours. Then, the netranic acid was adjusted to various concentrations and then replaced with DMEM medium and further incubated for 24 hours. 10 µl of MTT solution [3- (4,5-Dimethyl-thiazole-2-yl) 2,5-diphenyl tetrazolium bromide: 5 mg / ml] was added to the culture medium, and left for 4 hours. 100 μl of DMSO solution was added per well, followed by stirring for 20 minutes, and the absorbance was measured at 570 nm with a microplate reader. Cell proliferation was calculated by the following equation.

The results of this experiment are shown in Table 1 below.

Concentration of Tranexamic Acid (µg / ml) Cell proliferation rate (%) ^* Fibroblast Keratinocyte Pigment cells 0.3 0 0 0 0.5 0 0 0 1.0 0 0 -50 5.0 0 0 -70 10 0 0 -75 50 0 0 -76 100 0 0 -95 ^* Average of 3 runs.

As shown in Table 1, the tranexamic acid has an inhibitory effect only on the proliferation of melanocytes without inhibiting the proliferation of fibroblasts and keratinocytes, and proliferates the cells as the concentration of the tranexamic acid increases. Inhibitory effect increased. Therefore, the composition containing the tranexamic acid of the present invention is very excellent in inhibiting the growth of melanocytes, it can be seen that the melanocyte growth inhibitory effect increases concentration-dependently to the tranexamic acid.

Example 2: Experiment of melanin production inhibitory effect of tranexamic acid

Melanosite was used for the mouse-derived B-16 melanoma cell line (ATCC CRL 6323). Melanoma cell lines were inoculated in DMEM medium containing 4.5 g / l glucose, 10% fetal bovine serum and 1% antibiotic and incubated for 24 hours under 37 ° C 5% CO ₂ conditions in a 50 ml T-flask. Thereafter, cells were separated by treatment with 0.05% trypsin containing 0.02% EDTA, and then inoculated in a 50 ml T-flask and incubated for 48 hours. At this time, the cell number was 5.76 × 10 ⁶ cells / flask. The melanoma cells cultured by diluting in DMEM medium were treated with appropriate concentrations of tranexamic acid and incubated at 37 ° C. for 5 days. Thereafter, all of the medium was removed, cells were treated with 1 ml of PBS containing 0.02% EDTA and 0.05% trypsin, and then cells were collected by centrifugation for 5 minutes. It was treated with 5% trichloroacetate (TCA), stirred and centrifuged to wash the precipitated melanin with PBS. 1N NaOH was dissolved and dissolved in the precipitated melanin, and the absorbance was measured at 475 nm. Melanin concentrations were determined from standard concentration curves of synthetic melanin (Sigma). Melanin synthesis inhibition was calculated by the following equation (2).

The results of the experiment are shown in Table 2 below.

Concentration of Tranexamic Acid (µg / ml) Melanin synthesis inhibition rate (%) ^* One 49.5 5 52.0 10 85.4 50 92.3 100 96.0 ^* Average of 3 runs.

As shown in Table 2, the melanin production inhibition rate of melanocytes in the melanocytes of tranexamic acid is very excellent, the melanin production inhibition rate increased depending on the concentration of the tranexamic acid. Therefore, it can be seen that the composition containing the tranexamic acid of the present invention is very excellent in the whitening effect by the inhibition of melanin production in melanocytes.

Example 3: Comparison of Cytotoxicity between Tranexamic Acid and Hydroquinone

Human normal melanocytes were inoculated to 1 × 10 ⁷ cells in each well of a 96-well microplate and incubated in DMEM medium for 24 hours. Then, the trimexamic acid and hydroquinone were adjusted to various concentrations and then replaced with serum-free DMEM medium, followed by further incubation for 24 hours. 10 [mu] l of MTT solution [3- (4,5-Dimethyl-thiazole-2-yl) 2,5-diphenyl tetrazolium bromide: 5 mg / ml] was added to the culture solution, left for 4 hours, and then discarded. 100 μl of DMSO solution was added per well, followed by stirring for 20 minutes, and the absorbance was measured at 570 nm with a microplate reader. Cell viability was calculated by the following equation.

The results of this experiment are shown in Table 3 below.

Concentration of Tranexamic Acid (µg / ml) Cell survival rate (%) ^* Tranexamic acid Hydroquinone One 0 -30 5 0 -70 10 0 -80 50 0 -90 100 0 -100 ^* Average of 3 runs.

As shown in Table 3, Tranexamic acid was not cytotoxic at this concentration, but hydroquinone known as a whitening agent with excellent whitening effect showed a strong stimulation enough to kill melanocytes. Thus, it can be seen that the composition comprising the tranexamic acid of the present invention is a safe substance without cytotoxicity.

Hereinafter, examples of the formulation of the present invention include a softening lotion, a convergent lotion, a nourishing lotion, a nourishing cream, a massage cream, an essence and a pack, but the formulation of a cosmetic including the composition of the present invention is not limited thereto.

Formulation Example 1 Flexible Lotion

ingredient Content (% by weight) Tranexamic acid 0.01 glycerin 6.0 1,3-butylene glycol 3.0 PEG 1500 1.0 Allantoin 0.1 DL-panthenol 0.3 EDTA-2Na 0.02 Benzophenone-9 0.04 Sodium hyaluronate 5.0 ethanol 10.0 Octicdodeceth-16 0.2 Polysorbate 20 0.2 Preservative, fragrance, coloring a very small amount Distilled water Remaining amount Sum 100

Formulation Example 2: Converging Cosmetic Water

ingredient Content (% by weight) Tranexamic acid 0.01 glycerin 2.0 1,3-butylene glycol 2.0 Allantoin 0.2 DL-panthenol 0.2 EDTA-2Na 0.02 Benzophenone-9 0.04 Sodium hyaluronate 3.0 ethanol 15.0 Polysorbate 20 0.3 Witch hazel extract 2.0 Citric acid a very small amount Preservative, fragrance, coloring a very small amount Distilled water Remaining amount Sum 100

Formulation Example 3: Nutrients

ingredient Content (% by weight) Tranexamic acid 0.01 Glyceryl Stearate SE 1.5 Stearyl alcohol 1.5 lanolin 1.5 Polysorbate 1.3 Sorbitan stearate 0.5 Cured Vegetable Oil 1.0 Mineral oil 5.0 Squalane 3.0 Trioctanoine 2.0 Dimethicone 0.8 Tocopherol Acetate 0.5 Carboxyvinyl Polymer 0.12 glycerin 5.0 1,3-butylene glycol 3.0 Sodium hyaluronate 5.0 Triethanolamine 0.12 Preservative, fragrance, coloring a very small amount Distilled water Remaining amount Sum 100

Formulation Example 4: Nutrition Cream

ingredient Content (% by weight) Tranexamic acid 0.01 Lipophilic monostearate 2.0 Cetearyl Alcohol 2.2 Stearic acid 1.5 Beeswax 1.0 Polysorbate 60 1.5 Sorbitan stearate 0.6 Cured Vegetable Oil 1.0 Squalane 3.0 Mineral oil 5.0 Trioctanoine 5.0 Dimethicone 1.0 Sodium hyaluronate 0.1 glycerin 5.0 Betaine 3.0 Triethanolamine 1.0 Preservative, fragrance, coloring a very small amount Distilled water Remaining amount Sum 100

Formulation Example 5: Massage Cream

ingredient Content (% by weight) Tranexamic acid 0.01 Lipophilic Monostearic Acid Glycerin 1.5 Stearyl alcohol 1.5 Stearic acid 1.0 Polysorbate 60 1.5 Sorbitan stearate 0.6 Isostearyl Isosterate 5.0 Squalane 5.0 Mineral oil 35.0 Dimethicone 0.5 Hydroxyethyl cellulose 0.12 glycerin 6.0 Triethanolamine 0.7 Preservative, fragrance, coloring a very small amount Distilled water Remaining amount Sum 100

Formulation Example 6: Essence

ingredient Content (% by weight) Tranexamic acid 0.01 glycerin 10.0 Betaine 5.0 PEG 1500 2.0 Allantoin 0.1 DL-panthenol 0.3 EDTA-2Na 0.02 Benzophenone-9 0.04 Hydroxyethyl cellulose 0.1 Sodium hyaluronate 8.0 Carboxyvinyl Polymer 0.2 Triethanolamine 0.18 Octyldodecanol 0.3 Octyldodeceth-16 0.4 ethanol 6.0 Preservative, fragrance, coloring a very small amount Distilled water Remaining amount Sum 100

Formulation Example 7: Pack

ingredient Content (% by weight) Tranexamic acid 0.01 Polyvinyl alcohol 15.0 Cellulose gum 0.15 glycerin 3.0 PEG 1500 2.0 Chicdestrin 0.15 DL-panthenol 0.4 Allantoin 0.1 Monomethylammonium Glycyric Acid 0.3 Nicotinamide 0.5 ethanol 6.0 PEG 40 Cured Castor Oil 0.3 Preservative, fragrance, coloring a very small amount Distilled water Remaining amount Sum 100

Example 4: Determination of the whitening effect of the cosmetic composition

The whitening effect of the cosmetic composition of the present invention was measured in 60 healthy Korean females aged 30-40 years. The subjects were randomly divided into two groups, each containing a nourishing cream containing 0.01% of tranexamic acid and a nourishing cream replacing the tranexamic acid of Formulation Example 4 with purified water (Comparative Example). After washing every morning and evening twice, an appropriate amount was applied continuously to the left and right side of the face for 2 months. The whitening effect was evaluated by observing the degree of facial improvement after the end of the test.

The results of this experiment are shown in Table 11 below.

division Effective (persons) Slightly valid (persons) Void (persons) Effectiveness% Formulation Example 4 24 5 One 88.3 Comparative example One 4 25 10.0

As shown in Table 11, the nutrition cream of Formulation Example 4 showed a higher whitening effect than the composition of the comparative example. In addition, skin irritation could not be observed in the subjects who applied the nutrition cream of Formulation Example 4 to the skin. Therefore, it can be seen that the cosmetic composition comprising the tranexamic acid of the present invention has a very excellent whitening effect.

Example 5 Experiment of Formulation Stability of Cosmetic Compositions Containing Tranexamic Acid

After the flexible lotion of Formulation Example 1 was left at 45 ° C. for 1 week to 12 weeks, the change of the content of tranexamic acid in the cosmetic composition was analyzed. 5 g of the sample of the cosmetic composition was suspended in 10 ml of isopropyl alcohol for 10 minutes, followed by sonication for 10 minutes, and then applied to 60 ml of methanol. After sonication, the resultant was filtered with a 0.45 μm filter and each sample was purified by HPLC. It was quantitated by (C ₁₈ , UV 325 nm, 30).

The results of this experiment are shown in Table 12 below.

time 1 week 2 weeks 3 weeks 4 Weeks 5 Weeks 6 Weeks Week 7 8 Weeks 9 Weeks 10 Weeks Week 11 12 Weeks content 97.6 97.5 97.4 96.7 96.6 96.4 96.4 96.2 96.0 96.0 96.0 96.0

As shown in Table 4, the cosmetic composition of the present invention containing tranexamic acid showed little change in the content of the tranexamic acid even after 3 months. Therefore, it can be seen that the cosmetic composition comprising the tranexamic acid of the present invention has excellent stability of the formulation.

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.

As described in detail above, the present invention provides a composition for inhibiting melanocyte proliferation and a cosmetic composition for skin whitening comprising a tranexamic acid as an active ingredient. The composition of the present invention has an excellent whitening effect that effectively inhibits melanin synthesis by inhibiting the proliferation of melanocytes without inhibiting the proliferation of fibroblasts and keratinocytes, etc., and has high skin safety and excellent stability in the formulation. Do.

Claims (4)

A cosmetic composition for skin whitening comprising tranexamic acid as an active ingredient. Melanosite proliferation inhibiting composition comprising a tranexamic acid as an active ingredient. The cosmetic composition according to claim 1, wherein the content of the tranexamic acid is 0.0001-10.0 wt% based on the total weight of the cosmetic composition. The group of claim 1 wherein the composition consists of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray Cosmetic composition for skin whitening, characterized in that it has a formulation selected from.