Skin-whitening composition

Abstract

To provide a component that can enhance melanogenesis inhibitory effect.SOLUTION: A skin-whitening composition contains (A) at least one selected from the group consisting of tranexamic acid, a derivative thereof and salts thereof and (B) extract from plants of Curcuma, Zingiberaceae. The skin-whitening composition can enhance melanogenesis inhibitory effect of tranexamic acid.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a whitening composition having an enhanced melanin production inhibitory effect by tranexamic acid, its derivatives, and their salts (hereinafter also referred to as "tranexamic acids").

Background Art

[0002] Freckles are a symptom in which the balance between melanin production and metabolism is disrupted and melanin accumulates excessively in epidermal cells. The causes of such symptoms include inflammation, hormonal imbalance, genetic factors, etc., and are particularly promoted by exposure to ultraviolet rays. Therefore, components for suppressing melanin production are used as whitening agents in external and internal preparations.

[0003] As whitening components that suppress melanin production, tranexamic acid and its derivatives (for example, Patent Document 1), ascorbic acid and its derivatives (for example, Patent Document 2), etc. have been known for a long time. In recent years, it has also been reported that an extract of Ougon, a plant of the genus Tatsunamisou in the Lamiaceae family, has an action of suppressing melanin uptake (for example, Patent Document 3).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0005] Although tranexamic acids and ascorbic acids have been used as whitening ingredients for a long time, their actual whitening effects are not fully satisfactory. In addition, although an inhibitory effect on melanin uptake has been reported for saffron extracts, a high concentration of the extract is required to exhibit the effect, making formulation difficult, and thus it is not suitable for practical use as a whitening ingredient.

[0006] Therefore, an object of the present invention is to provide a whitening composition capable of enhancing the melanin production inhibitory effect.

Means for Solving the Problems

[0007] As a result of intensive studies, the present inventor has found that by combining an extract of a plant belonging to the genus Curcuma of the Zingiberaceae family, which does not exhibit a melanin production inhibitory effect alone, with tranexamic acids, the melanin production inhibitory effect by tranexamic acids can be enhanced. The present invention has been completed by further studies based on this finding.

[0008] That is, the present invention provides an invention in the following aspects. Item 1. A whitening composition comprising (A) at least one selected from the group consisting of tranexamic acid, its derivatives, and their salts, and (B) an extract of a plant belonging to the genus Curcuma of the Zingiberaceae family. Item 2. The whitening composition according to Item 1, wherein the plant belonging to the genus Curcuma of the Zingiberaceae family is selected from the group consisting of turmeric, mango ginger, har turmeric, gaduts, and kusuri turmeric. Item 3. The whitening composition according to Item 1 or 2, further comprising (C) an extract of a plant belonging to the genus Perilla of the Lamiaceae family. Item 4. The whitening composition according to Item 3, wherein the plant belonging to the genus Perilla of the Lamiaceae family is selected from the group consisting of saffron, skullcap, and hanshirene. Item 5. The whitening composition according to any one of Items 1 to 4, wherein the (B) component is contained in an amount of 0.01 to 10 parts by weight per 1000 parts by weight of the (A) component. Item 6. The whitening composition according to any one of Items 3 to 5, which contains 0.01 to 12 parts by weight of the component (C) per 1000 parts by weight of the component (A). Item 7. The whitening composition according to any one of Items 1 to 6, which is an external composition.

Effects of the Invention

[0009] According to the present invention, there is provided a whitening composition capable of enhancing the melanin production inhibitory effect.

Modes for Carrying Out the Invention

[0010] The whitening composition of the present invention is characterized by containing (A) tranexamic acids (hereinafter also referred to as the “component (A)”) and (B) an extract of a plant of the genus Curcuma of the Zingiberaceae family (hereinafter also referred to as the “component (B)”). Hereinafter, the whitening composition of the present invention will be described in detail.

[0011] (A) Tranexamic acids The whitening composition of the present invention contains, as the component (A), tranexamic acid, its derivatives and / or their salts.

[0012] Tranexamic acid is a compound also called trans-4-(aminomethyl)cyclohexane carboxylic acid, and is a known drug known to have an anti-bleeding effect, an anti-allergic effect, an anti-inflammatory effect, a melanin production inhibitory effect, etc. by its anti-plasmin action.

[0013] Derivatives of tranexamic acid are not particularly limited as long as they are pharmaceutically or cosmetically acceptable. Specifically, examples include tranexamic acid dimers, tranexamic acid esters, tranexamic acid vitamin esters, tranexamic acid alkylamides, tranexamic acid phenyl esters, and N,N-maleoyliminotranexamic acid. Specific examples of tranexamic acid esters include alkyl esters having 1 to 30 carbon atoms; phenyl esters which may be substituted with an alkyl group having 1 to 30 carbon atoms, a halogen atom, a carboxyl group, etc. Specific examples of tranexamic acid alkylamides include tranexamic acid methylamide, tranexamic acid ethylamide, and the like. These derivatives of tranexamic acid may be used alone or in combination of two or more.

[0014] Salts of tranexamic acid and / or its derivatives are not particularly limited as long as they are pharmaceutically or cosmetically acceptable. Specifically, examples include inorganic acid salts such as hydrochloride, nitrate, and sulfate; organic acid salts such as acetate, lactate, maleate, fumarate, tartrate, citrate, and methanesulfonate; organic amine salts such as monoethanolamine salt, diethanolamine salt, and triethanolamine salt; ammonium salts; alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as magnesium salt, and the like. These salts may be used alone or in combination of two or more.

[0015] In the whitening composition of the present invention, as the component (A), one kind may be selected and used from tranexamic acid, salts of tranexamic acid, derivatives of tranexamic acid, and salts of derivatives of tranexamic acid, or two or more kinds may be used in combination.

[0016] Among these component (A), from the viewpoint of further enhancing the melanin production inhibitory effect, tranexamic acid or its salt is preferably used, and tranexamic acid is more preferably used.

[0017] In the whitening composition of the present invention, the content of component (A) may be appropriately set according to the suppression of melanin production and the like that should be provided in the whitening composition. For example, it is 0.1 to 10% by weight, preferably 0.5 to 10% by weight, more preferably 1 to 10% by weight, and still more preferably 1.5 to 10% by weight. Further, since the whitening composition of the present invention is excellent in the effect of enhancing the melanin production inhibitory effect, even if the content of component (A) is relatively small, an excellent melanin production inhibitory effect can be exhibited. From such a viewpoint, preferred examples of the content of component (A) in the whitening composition of the present invention include, for example, 0.1 to 8% by weight, preferably 0.1 to 5% by weight, more preferably 0.1 to 3% by weight, still more preferably 0.1 to 2.5% by weight, and even more preferably 0.1 to 2.2% by weight.

[0018] (B) Extracts of plants of the genus Curcuma of the Zingiberaceae family The whitening composition of the present invention contains, as component (B), a plant extract of the genus Curcuma of the family Zingiberaceae. Component (B) alone does not show a melanin production inhibitory effect, but by combining with component (A), the melanin production inhibitory effect can be enhanced.

[0019] Extracts of plants of the genus Curcuma of the family Zingiberaceae are known components having antioxidant action, anti-aging action, and the like. Specific examples of the plant extract of the genus Curcuma of the family Zingiberaceae include extracts of Curcuma longa Linne, extracts of Curcuma amada Roxb., extracts of Curcuma aromatica Salisb., extracts of Curcuma zedoaria Roscoe, and extracts of Curcuma domestica Valeton. These extracts may be used alone or in combination of two or more.

[0020] Among the above-mentioned extracts, from the viewpoint of further enhancing the effect of enhancing the melanin production inhibitory effect, the extract of turmeric is preferably mentioned. The extract of turmeric is indicated as an external preparation raw material standard, etc. as turmeric extract. Specifically, the extract of turmeric can be obtained by subjecting the rhizome of turmeric to an extraction treatment using an extraction solvent. Examples of the extraction solvent used for the extraction treatment of turmeric include water; lower alcohols such as ethanol and isopropanol; polyhydric alcohols such as 1,3-butylene glycol (BG), propylene glycol, and glycerin; polar solvents such as mixtures thereof. From the viewpoint of further enhancing the effect of enhancing the melanin production inhibitory effect, preferably, a mixed solvent of water and 1,3-butylene glycol (BG) is mentioned, more preferably an aqueous solution with a BG concentration of 20 to 80% by weight, still more preferably 40 to 60% by weight, even more preferably 45 to 55% by weight. The extract obtained by the solvent extraction treatment may be used as it is in a liquid state, but may also be subjected to treatments such as concentration and drying as needed and used as a concentrate or a dried product. Further, after concentration or drying, the obtained concentrate or dried product may be washed with a non-soluble solvent for purification and used, or it may also be dissolved or suspended in a suitable solvent and used. Also, as turmeric extract, commercially available ones can be simply used. For example, they are commercially available from Yamada Pharmaceutical Co., Ltd., Ichimaru Pharcos Co., Ltd., Maruzen Pharmaceutical Co., Ltd., NOF Corporation, etc.

[0021] The content of the component (B) in the whitening composition of the present invention is not particularly limited, and examples thereof include 0.000001 to 10% by weight in terms of the dry weight conversion amount. From the viewpoints of further enhancing the effect of enhancing the melanin production inhibitory effect, etc., the content of the component (B) is preferably 0.000005 to 0.1% by weight, more preferably 0.00001 to 0.05% by weight, still more preferably 0.00005 to 0.01% by weight, even more preferably 0.00005 to 0.001% by weight, and even more preferably 0.00005 to 0.0001% by weight in terms of the dry weight conversion amount.

[0022] In the whitening composition of the present invention, the ratio of component (A) to component (B) is determined by the content of each of the above components. From the viewpoint of further enhancing the effect of enhancing the melanin production inhibitory effect, etc., the content of component (B) per 1000 parts by weight of component (A) is preferably 0.01 to 10 parts by weight, more preferably 0.02 to 5 parts by weight, still more preferably 0.03 to 3 parts by weight, even more preferably 0.03 to 1.5 parts by weight, and even more preferably 0.03 to 0.5 parts by weight.

[0023] (C) Extracts of plants of the genus Glechoma of the Lamiaceae family The whitening composition of the present invention can further contain an extract of a plant of the genus Scutellaria of the family Lamiaceae as component (C). By further containing component (C), the melanin production inhibitory effect can be further enhanced. Further, even when component (C) is used at a low concentration such that it does not exhibit a melanin production inhibitory effect alone, the melanin production inhibitory effect can be effectively enhanced.

[0024] Extracts of plants of the genus Scutellaria of the family Lamiaceae are known components having anti-allergic action, antibacterial action, astringent action, moisturizing action, melanin uptake inhibitory action, etc. Specific examples of the plant extract of the genus Scutellaria of the family Lamiaceae include extracts of Scutellaria baicalensis Georgi, extracts of Scutellaria lateriflora Linne, and extracts of Scutellaria barbata D. Don.). These plant extracts may be used alone or in combination of two or more.

[0025] Among the above extracts, from the viewpoint of further enhancing the effect of enhancing the melanin production inhibitory effect, preferably the extract of Coptis japonica can be mentioned. The extract of Coptis japonica is shown as an external medicine raw material standard etc. as Coptis japonica extract. Specifically, the extract of Coptis japonica can be obtained by subjecting the root of Coptis japonica to an extraction treatment using an extraction solvent. Examples of the extraction solvent used for the extraction treatment of Coptis japonica include water; lower alcohols such as ethanol and isopropanol; polyhydric alcohols such as 1,3-butylene glycol (BG), propylene glycol, and glycerin; polar solvents such as a mixture thereof. From the viewpoint of further enhancing the effect of enhancing the melanin production inhibitory effect, preferably, a mixed solvent of water and 1,3-butylene glycol (BG) can be mentioned, more preferably an aqueous solution with a BG concentration of 20 to 80% by weight, even more preferably 40 to 60% by weight, and still more preferably 45 to 55% by weight. The extract obtained by the solvent extraction treatment may be used as it is in a liquid state, but may also be subjected to treatments such as concentration and drying as necessary and used as a concentrate or a dried product. Further, after concentration or drying, the obtained concentrate or dried product may be washed with a non-soluble solvent for purification and used, or it may also be dissolved or suspended in a suitable solvent and used. Further, as Coptis japonica extract, commercially available ones can be simply used. For example, it is commercially available from Yamada Pharmaceutical Co., Ltd., Ichimaru Pharcos Co., Ltd., Maruzen Pharmaceutical Co., Ltd., etc.

[0026] The content of component (C) in the composition for whitening of the present invention is not particularly limited, and examples thereof include 0.000001 to 10% by weight in terms of dry weight conversion. From the viewpoint of further enhancing the effect of suppressing melanin production, the content of component (C) is preferably 0.000005 to 10% by weight, more preferably 0.0001 to 10% by weight, still more preferably 0.0005 to 10% by weight, in terms of dry weight conversion. Further, since the composition for whitening of the present invention is excellent in enhancing the effect of suppressing melanin production, even a small amount of component (C) can effectively enhance the effect of suppressing melanin production. From such a viewpoint, preferred examples of the content of component (C) include 0.000001 to 0.1% by weight, preferably 0.000001 to 0.05% by weight, more preferably 0.000001 to 0.01% by weight, still more preferably 0.000001 to 0.005% by weight, even more preferably 0.000001 to 0.003% by weight, and still even more preferably 0.000001 to 0.0015% by weight.

[0027] In the composition for whitening of the present invention, the ratio of component (A) to component (C) is determined by the content of each component described above. From the viewpoint of further enhancing the effect of suppressing melanin production, the content of component (C) per 1000 parts by weight of component (A) is preferably 0.01 to 12 parts by weight, more preferably 0.4 to 12 parts by weight. Further, since the composition for whitening of the present invention is excellent in enhancing the effect of suppressing melanin production, even a small amount of component (C) relative to component (A) can effectively enhance the effect of suppressing melanin production. From such a viewpoint, preferred examples of the content of component (C) per 1000 parts by weight of component (A) include 0.01 to 8 parts by weight, preferably 0.01 to 2.5 parts by weight, more preferably 0.01 to 1.5 parts by weight, still more preferably 0.01 to 0.8 parts by weight, and even more preferably 0.01 to 0.6 parts by weight.

[0028] Other ingredients In addition to the above components, the whitening composition of the present invention may contain other pharmacological components as necessary. Examples of such pharmacological components include anti-inflammatory agents, antioxidants, bactericides, cooling agents, vitamins, mucopolysaccharides, and the like.

[0029] Furthermore, the whitening composition of the present invention may contain a base and additives as necessary to form a desired dosage form. Such bases and additives are not particularly limited as long as they are pharmaceutically acceptable. Examples include aqueous bases such as water, lower alcohols (ethanol, isopropanol, etc.), polyhydric alcohols (glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, etc.); oily bases such as natural-derived oils, mineral oils, ester oils, fatty acid alkyl esters, fatty acids, fatty acid esters, higher alcohols, etc.; surfactants; additives such as cooling agents, preservatives, flavoring agents, coloring agents, thickening agents, pH adjusters, wetting agents, stabilizers, antioxidants, ultraviolet absorbers, chelating agents, adhesives, buffers, solubilizing aids, solubilizers, preservatives, and the like.

[0030] Form of preparation Moreover, the whitening composition of the present invention may be either an internal preparation or an external preparation, but is preferably an external preparation. As the external preparation, any dosage form such as a topical pharmaceutical, a cosmetic, a skin cleanser, etc. may be used as long as it is for external use.

[0031] The dosage form of the whitening composition of the present invention is not particularly limited and may be any of liquid, solid, semi-solid (cream-like, gel-like, ointment-like, paste-like), etc. Also, the whitening composition of the present invention may be a non-emulsified preparation such as an aqueous preparation or an oily preparation, or an emulsified preparation such as an oil-in-water type emulsified preparation or a water-in-oil type emulsified preparation.

[0032] As the dosage form of the composition for whitening of the present invention, specifically, external skin pharmaceuticals such as liquid agents (including lotions, sprays, aerosols, and milky lotions), water-soluble ointments, oily ointments, creams, foams, gels, patches, etc.; cosmetics such as ointments, creams, milky lotions, lotions, toners, packs, gels, etc.; skin cleansers such as body shampoos, hair shampoos, rinses, etc. can be mentioned. The preparation into these dosage forms can be carried out by formulating according to known methods described in the General Rules of the Sixteenth Revised Japanese Pharmacopoeia using additives according to the dosage form. It can be carried out by formulating using additives according to the dosage form in accordance with known methods described in the General Rules of the Sixteenth Revised Japanese Pharmacopoeia.

[0033] Use Since the composition for whitening of the present invention can suppress the production of melanin, it is suitably used for the prevention or improvement of skin freckles, chloasma, dullness, liver spots, senile pigment spots, darkening due to physical irritation, etc.

Example

[0034] Examples are shown below to more specifically explain the present invention, but the present invention is not limited thereto.

[0035] Using tranexamic acid and the saffron extract material and / or turmeric extract material shown in Table 1 (in the table, BG represents 1,3-butylene glycol, and the numerical values shown in % are based on weight), the compositions shown in Table 2 were prepared and the melanin production inhibitory effect was evaluated.

[0036]

Table 1

[0037] <Melanin production inhibitory effect> Tranexamic acid was mixed with the saffron extract material and / or the turmeric extract material shown in Table 1 and diluted with PBS to the concentrations shown in Table 2 to prepare specimens. 50 μL of the specimen was added to a skin three-dimensional culture model (KURABO MEL-300, Asian donor) and cultured for 24 hours. After culturing, the skin three-dimensional culture model was washed with PBS and observed under a microscope. After irradiating the skin model with 30 mJ / cm 2 of UV-B, it was further cultured for 24 hours. Separately, the same operation was performed using BG diluted 200-fold with PBS instead of the specimen (control).

[0038] The above specimen addition and UV-B irradiation were repeated every 24 hours until the skin model in the control became cell melanized. Specifically, a series of operations of specimen addition and UV-B irradiation were repeated 6 times. Then, the skin model was washed with PBS, observed under a microscope, and the number of viable cells was measured using a Cell Counting Kit-8.

[0039] The skin model was disrupted by ultrasonic waves. 100 μL of a protein extraction solution (M-PER TM Mammalian Protein Extraction Reagent, Thermo) was added to the disrupted tissue and centrifuged at 10,000 rpm for 10 minutes. The supernatant was removed, and 100 μL of 4N NaOH was added to the pellet (melanin) precipitated at the bottom, boiled for 20 minutes, and melanin was extracted. The absorbance (405 nm) of the melanin extract was measured. The absorbance of the melanin extract was corrected by the number of viable cells to obtain the amount of melanin in each specimen. The relative amount (%) of the amount of melanin by each specimen was derived when the amount of melanin in the control was set to 100%. The value (%) obtained by subtracting the relative amount (%) of the amount of melanin by each specimen from the amount of melanin in the control (100%) was derived as the melanin production inhibition score. If the melanin production inhibition score is a positive number, a melanin production inhibition effect is recognized. The results are shown in Table 2.

[0040]

Table 2

[0041] As shown in Table 2, the (A) component showed a weak melanin production inhibitory score (Comparative Example 1), and no melanin production inhibitory score was observed for the (B) component and the (C) component (Comparative Examples 2 and 3). On the other hand, although no melanin production inhibitory score was observed for the (B) component, the combination of the (A) component and the (B) component enhanced the melanin production inhibitory effect (Examples 1 to 5). Further, as shown by the comparison between Example 1 and Example 2, when the (C) component was further combined (Example 2), the melanin production inhibitory effect was further enhanced even though the (C) component was at a low concentration at which no melanin production inhibitory score was observed.

Claims

1. A whitening composition comprising (A) at least one member selected from the group consisting of tranexamic acid, its derivatives, and salts thereof, and (B) an extract of a plant of the genus Curcuma in the family Zingiberaceae.

2. 2. The whitening composition according to claim 1, wherein the plant of the genus Curcuma of the family Zingiberaceae is selected from the group consisting of turmeric, mango ginger, yellow turmeric, zedoary, and turmeric.

3. The whitening composition according to claim 1 or 2, further comprising (C) an extract of a plant of the genus Scutellaria in the family Lamiaceae.

4. The whitening composition according to claim 3, wherein the plant of the genus Scutellaria of the family Lamiaceae is selected from the group consisting of Scutellaria baicalensis, Skullcap, and Chinese laurel.

5. The whitening composition according to any one of claims 1 to 4, comprising 0.01 to 10 parts by weight of said component (B) per 1000 parts by weight of said component (A).

6. The whitening composition according to any one of claims 3 to 5, comprising 0.01 to 12 parts by weight of said component (C) per 1000 parts by weight of said component (A).

7. The whitening composition according to any one of claims 1 to 6, which is a composition for external use.

Images