Title of Invention	"A COMPOSITION FOR PREVENTING OR IMPROVING PIGMENTATION"
Abstract	A composition for preventing or improving pigmentation, the composition comprising: at least one member (A) selected from the group consisting of adenosine 5'-monophosphates and salts thereof; and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones wherein the composition comprising said at least one member (A) in a total proportion of 0.05 to 10% by weight based on a total weight of the composition and said at least one member (B) in a total proportion of 0.00001 to 100 parts by weight per part by weight of a total weight of said at least one member (A).

Title of Invention

"A COMPOSITION FOR PREVENTING OR IMPROVING PIGMENTATION"

Abstract

A composition for preventing or improving pigmentation, the composition comprising: at least one member (A) selected from the group consisting of adenosine 5'-monophosphates and salts thereof; and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones wherein the composition comprising said at least one member (A) in a total proportion of 0.05 to 10% by weight based on a total weight of the composition and said at least one member (B) in a total proportion of 0.00001 to 100 parts by weight per part by weight of a total weight of said at least one member (A).

Full Text	DESCRIPTION COMPOSITION FOR PREVENTION OR ALLEVIATION OF PIGMENTATION TECHNICAL FIELD The present invention relates to a composition for preventing or improving pigmentation of the skin that can prevent or improve effectively skin pigmentation. The present invention also relates to a method for preventing or improving pigmentation of the skin. BACKGROUND OF THE INVENTION Pigmentation of the skin, such as chloasma, freckles, and the like, is a serious aesthetic problem particularly for women. Generally, the onset of chloasma and freckles on the skin is induced by the precipitation of melanin pigment formed in the skin cells when the skin is stimulated by exposure to ultraviolet light and the like. Therefore, pigmentation of the skin, such as chloasma, freckles, and the like, has heretofore been prevented or improved by the use of an externally-applied composition comprising arbutin, kojic acid, ascorbic acid, ascorbic acid derivatives, ellagic acid, 4-n-butylresorcinol, linolic acid, tranexamic acid, chamomile extract, etc., which directly or indirectly inhibit the formation of melanin pigment (e.g., Non-patent Document 1). However, these externally-applied compositions are disadvantageous in that the effect of improving the pigmentation is slow and insufficient. Ubiquinone is known to have an antioxidant action, but the effect of preventing or improving pigmentation is inadequate and is not satisfactory. In contrast, Adenosine 5'-monophosphate (hereinafter referred to as AMP) is already known to have an action for improving the pigmentation of the skin, and can be suitably used in externally-applied compositions for improving the pigmentation of the skin. However, no case to date has been reported in which a specific melanin formation inhibitor or ubiquinone is used in combination with AMP until now, and thus the effect obtained by the combined use thereof is not known. [Non-patent Document 1] "Keshohin no Yuyosei: Hyokagijutu no Shinpo to Shorai Tenbo" (Functional Cosmetology Substantiation of Cosmetics Efficacy: Recent Progress and Future Promise of Evaluation Techniques); edited by Katsuiyuki TAKEDA, Shotaro HARADA, and Masanori ANDO; Nippon Keshohin Gijutsushakai;Yakuji Nippo; pp. 149 to 159. DISCLOSURE OF THE INVENTION PROBLEM TO BE SOLVED BY THE INVENTION The present invention aims to provide a composition for preventing or improving pigmentation of the skin that can effectively prevent or improve the skin pigmentation. The present invention also aims to provide a method for effectively preventing or improving pigmentation of the skin. MEANS FOR SOLVING THE PROBLEM The present inventors carried out extensive research to solve the above-described problems, and found that the action of preventing or improving pigmentation of the skin is synergistically enhanced by the combined use of at least one member (A) selected from the group consisting of AMP and salts thereof; and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones. The inventors conducted further research and accomplished the present invention based on these findings. More specifically, the present invention encompasses the following aspects. Item 1. A composition for preventing or improving pigmentation, the composition comprising: at least one member (A) selected from the group consisting of adenosine 5'-monophosphates and salts thereof; and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones. Item 2. A composition according to item 1, comprising said at least one member (A) in a total proportion of 0.05 to 10% by weight based on a total weight of the composition. Item 3. A composition according to item 1, comprising said at least one member (B) in a total proportion of 0.00001 to 100 parts by weight per part by weight of a total weight of said at least one member (A) . Item 4. A composition according to item 1, comprising said at least one member (B) in a total proportion of 0.0001 to 50% by weight based on a total weight of the composition. Item 5. A composition according to item 1, wherein said at least one member (B) is selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, and salts thereof, and said at least one member (B) is contained in a total proportion of 0.1 to 100 parts by weight per part by weight of a total weight of said at least one member (A). Item 6. A composition according to item 1, wherein said at least one member (B) is selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, and salts thereof, and said at least one member (B) is contained in a total proportion of 0.01 to 50% by weight based on a total weight of the composition. Item 7. A composition according to item 1, wherein said at least one member (B) is chamomile extract, and said at least one member (B) is contained in a total proportion of preferably 0.00001 to 10 parts by weight as calculated in terms of solid content per part by weight of a total weight of said at least one member (A). Item 8. A composition according to item 1, wherein said at least one member (B) is chamomile extract, and said at least one member (B) is contained in a total proportion of 0.0001 to 0.5% by weight as calculated in terms of solid content. Item 9. A composition according to item 1, wherein said at least one member (B) is ubiquinone, and said at least one member (B) is contained in a total proportion of 0.001 to 100 parts by weight per part by weight of a total weight of said at least one member (A). Item 10. A composition according to item 1, wherein said at least one member (B) is ubiquinone, and said at least one member (B) is contained in a total proportion of 0.0001 to 50% by weight based on a total weight of the composition. Item 11. A composition according to item 1, being a cosmetic composition or a pharmaceutical composition. Item 12. A method for preventing or improving pigmentation, comprising applying, to human skin, at least one member (A) selected from the group consisting of adenosine 5'-monophosphates and salts thereof and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones. Item 13. A method according to item 12, comprising applying, to human skin, a composition of any one of items 1 to 11. Item 14. A method according to item 12, being a cosmetic method. Item 15. Use of at least one member (A) selected from the group consisting of adenosine 5'-monophosphate and salts thereof and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones for the production of a composition for preventing or improving skin pigmentation. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 shows delta values (A) of visual grading scores (indexes showing the improvement effects of skin pigmentation) of Formulation Example 1 (combined use of AMP2Na and arbutin), Comparative Formulation Example 1-1 (AMP2Na), and Comparative Formulation Example 1-2 (arbutin) in Test Example 1. Fig. 2 shows delta values (A) of visual grading scores (indexes showing the improvement effects of skin pigmentation) of Formulation Example 2 (combined use of AMP2Na and ellagic acid hydrate), Comparative Formulation Example 2-1 (AMP2Na), and Comparative Formulation Example 2-2 (ellagic acid hydrate) in Test Example 2. Fig. 3 shows delta values (A) of visual grading scores (indexes showing the improvement effects of skin pigmentation) of Formulation Example 3(combined use of AMP2Na and tranexamic acid), Comparative Formulation Example 3-1 (AMP2Na) and Comparative Formulation Example 3-2 (tranexamic acid) in Test Example 3. Fig. 4 shows delta values (A) of visual grading scores (indexes showing the improvement effects of skin pigmentation) of Formulation Example 4 (combined use of AMP2Na and 4-n-hexylresorcinol) , Comparative Formulation Example 4-1 (AMP2Na) and Comparative Formulation Example 4-2 (4-n-hexylresorcinol) in Test Example 4. Fig. 5 shows delta values (A) of visual grading scores (indexes showing the improvement effects of skin pigmentation) of Formulation Example 5 (combined use of AMP2Na and chamomile extract), Comparative Formulation Example 5-1 (AMP2Na) and Comparative Formulation Example 5-2 (chamomile extract) in Test Example 5. Fig. 6 shows delta values (A) of visual grading scores (indexes showing the improvement effects of skin pigmentation) of Formulation Example 6 (combined use of AMP2Na and coenzyme Q10), Comparative Formulation Example 6-1 (AMP2Na) and Comparative Formulation Example 6-2 (coenzyme Q10) in Test Example 6. BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. 1. Composition for preventing or improving skin pigmentation The composition for preventing or improving skin pigmentation of the invention comprises at least one member (hereinafter referred to as ingredient(s) (A)) selected from the group consisting of AMP and salts thereof. In the invention, there is no limitation on the salts of AMP used as the ingredient (s) (A) insofar as they can be added to cosmetics and externally-applied pharmaceutical compositions. Specific examples of the salts of AMP include alkali metal salts such as sodium salts, potassium salts, and the like; alkaline earth metal salts such as calcium salts, magnesium salts, barium salts, and the like; basic amino acid salts, such as arginine, lysine, and the like; ammonium salts, such as ammonium salts, tricyclohexyl ammonium salts, and the like; various alkanolamine salts such as monoethanolamine salts, diethanolamine salts, triethanolamine salts, monoisopropanolamine salts, diisopropanolamine salts, and triisopropanolamine, and the like. Among these, alkali metal salts, such as sodium salts and the like, are preferable. Specific examples of such alkali metal salts include adenosine monophosphate monosodium and adenosine monophosphate disodium. These salts of AMP may be used singly or in combination. The proportion of the ingredient (s) (A) added to the composition of the invention is not limited and can be suitably adjusted according to the form of the composition, kind of the ingredient (s) (A), expected effect, etc. As one example, the total proportion of the ingredient (s) (A) is in the range of 0.05 to 10% by weight, preferably 0.1 to 7% by weight, and more preferably 0.5 to 6% by weight based on the total weight of the composition for preventing or improving skin pigmentation. The composition for preventing or improving skin pigmentation of the invention comprises at least one member (hereinafter referred to as ingredient(s) (B)) selected from the group consisting of arbutins (chemical name: 4- hydroxyphenyl-p-D-glucopyranoside and 4-Hydroxyphenyl-oc-D-glucopyranoside), ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones in addition to the ingredient(s) (A). The above-mentioned arbutin may be either a- or P-arbutin. Specific examples of the above-mentioned 4-alkylresorcinol include 4-methylresorcinol, 4-ethylresorcinol, 4-n-propylresorcinol, 4-n-butylresorcinol, 4-n-pentylresorcinol, 4-n-hexylresorcinol, etc. Among these, 4-n-butylresorcinol, 4-n-pentylresorcinol, and 4-n-hexylresorcinol are preferable, and 4-n-butylresorcinol and 4-n-hexylresorcinol are more preferable. Among the above-mentioned ingredients (B), arbutin, ellagic acid, 4-alkylresorcinol, linolic acid, and tranexamic acid may be in the form of a salt insofar as they are cosmetically or pharmaceutically acceptable. Examples of these salts include alkali metal salts, alkaline earth metal salts, basic amino acid salts, ammonium salts, alkanolamine salts, etc. as well as above-mentioned examples of the salts of AMP. Chamomile extracts are extracts obtained by extracting flower and/or stem of Matricaria chamomilla using a solvent. Specifically, chamomile extracts can be obtained by extracting from the flower and/or stem of Matricaria chamomilla in water or an organic solvent, or a mixed liquid of water and an organic solvent at normal temperature or under warmed conditions. The flower and/or stem may be used as it is, or, as required, may be dried, chopped, crushed, compressed, or boiled for the extraction step. Examples of the organic solvent used for this extraction process include lower alcohols with a carbon number range of C1-C5 (e.g., methanol, ethanol, propanol, isopropanol, butanol, etc.), propylene glycol, 1,3-butylene glycol, acetone, ethyl acetate, chloroform, toluene, pentane, hexane, heptane, etc. and these solvents can be used singly or in combination. As the extracting solvent, water, lower alcohols with a carbon number range of C1-C5, or a mixture of such alcohols and water is preferable, and ethanol and the mixture of ethanol and water are particularly preferable. In the case of the mixture of lower alcohols with a carbon number range of C1-C5 and water, the proportion of the alcohol based on the total weight of the mixture is, for example, 0.01 to 100% by weight, preferably 5 to 55% by weight, and more preferably 45 to 55% by weight. Chamomile extracts are commercially available, and such commercially-available chamomile extracts can be used. In the invention, chamomile extracts may be used in the form of an extracted liquid, an extracted concentrate, purified matter, dried matter, a solution made using dried matter, or fractioned matter, etc. There is no limitation on the above-mentioned ubiquinones, and, for example, coenzyme Q6, coenzyme Q7, coenzyme Q8, coenzyme Q9, and coenzyme Q10 can be mentioned. Among these, coenzyme Q10 is preferable. The proportion of the ingredient (s) (B) added to the composition of the invention is not limited and can be suitably adjusted according to the form of the composition, the expected effect, and the like. As one example, the total proportion of the ingredient (s) (B) is in the range of 0.00001 to 100 parts by weight per part by weight of the total weight of ingredient(s) (A). More specifically, when the ingredient(s) (B) is arbutin, ellagic acid, 4-alkylresorcinol, linolic acid, tranexamic acid, and/or salts thereof, the total proportion of the ingredient (s) (B) is preferably 0.1 to 100 parts by weight, and more preferably 1 to 100 parts by weight, per part by weight of the total weight of ingredient(s) (A). For example, when the ingredient (s) (B) is chamomile extract, the total proportion of the ingredient(s) (B) is preferably 0.00001 to 10 parts by weight, and more preferably 0.0001 to 10 parts by weight, per part by weight of the total weight of ingredient (s) (A). As another example, when the ingredient(s) (B) is ubiquinone, the total proportion of the ingredient(s) (B) is preferably 0.001 to 100 parts by weight, and more preferably 0.01 to 100 parts by weight, per part by weight of a total weight of ingredient(s) (A). In the above-mentioned proportions of the ingredient (s) (B) , the proportion of chamomile extract is calculated in terms of solid content. With the combined use of the ingredients (A) and (B) in the above-mentioned proportions, the effects of preventing or improving skin pigmentation of both the ingredients (A) and (B) are synergistically enhanced, whereby more excellent pigmentation inhibitory effects are exhibited. The total proportion of ingredient(s) (B) is, for example, 0.0001 to 50% by weight based on the total weight of the composition for preventing or improving skin pigmentation. More specifically, when the ingredient(s) (B) is arbutin, ellagic acid, 4-alkylresorcinol, linolic acid, tranexamic acid, and/or salts thereof, the total proportion of the ingredient (s) (B) is, for example, 0.01 to 50% by weight, preferably 0.05 to 30% by weight, and more preferably 0.1 to 20% by weight. When the ingredient (s) (B) is chamomile extract, the total proportion of the ingredient (s) (B) is, for example, 0.0001 to 0.5% by weight, preferably 0.0005 to 0.3% by weight, and more preferably 0.001 to 0.2% by weight. When the ingredient (s) (B) is ubiquinone, the total proportion of the ingredient (s) (B) is, for example, 0.0001 to 50% by weight, preferably 0.001 to 30% by weight, and more preferably 0.01 to 20% by weight. In the above-mentioned proportions of the ingredient (s) (B), the proportion of chamomile extract is calculated in terms of solid content. The composition for preventing or improving skin pigmentation of the invention is formed into cosmetic compositions, externally-applied pharmaceutical compositions, and the like so that it is applied through the skin. In the invention, the externally-applied pharmaceutical compositions encompass externally-applied medical or quasi-medical drugs. Such externally-applied pharmaceutical compositions for preventing or improving skin pigmentation can take any form without limitation insofar as they are applicable to the skin or mucosa, such as an aqueous solution, a solubilized form, an emulsified form, a dispersed powder, a water/oil two-layer type, etc. Specific examples include solutions, oily preparations, lotions, liniments, emulsions, suspensions, creams, ointments, etc. Examples of cosmetic compositions include lotions; emollient emulsions, milky lotions, nourishing emulsions, cleansing emulsions, and like emulsions; emollient creams, massage creams, cleansing creams, makeup creams, and like creams; etc. The composition for preventing or improving pigmentation of the invention may also be formed into hair care products such as hair growth formula and the like. Examples of hair care products include hair tonics, hair creams, hair lotions, aerosols (air sprays), mousses, shampoos, rinses, liquids, etc. The composition for preventing or improving skin pigmentation of the invention may contain a wide range of known components added to-compositions applied to the skin or mucosa, such as cosmetic compositions, externally-applied pharmaceutical compositions, and the like. Examples of such ingredients include humectants, UV absorbers, UV dispersants, vitamins, plant extracts, astringents, anti-inflammatory agents (antiphlogistic agents), whiteners, cell activators, vasodilators, blood circulation accelerators, skin function accelerators, and the like in addition to surfactants, coloring agents (dyes, pigments), perfumes, preservatives, bactericides (antibacterials), thickeners, antioxidants, sequestering agents, refrigerants, deodorizers, and the like. Known bases or carriers can also be used in accordance with the above-mentioned various forms. Among the above-mentioned ingredients, examples of surfactants include anionic surfactants, such as salts of higher fatty acids, alkylsulfonates, polyoxyethylene alkyl ether sulfates, alkyl ether phosphates, W-acylamino acid salts, acyl W-methyltaurates, etc.; cationic surfactants, such as alkyltrimethyl ammonium chlorides, dialkyldimethyl ammonium chlorides, etc.; amphoteric surfactants, such as alkyl dimethylaminoacetic acid betaines, alkylamidodimethylaminoacetate betaines, 2-alkyl-N-carboxy-W-hydroxyimidazolinium betaines, etc.; nonionic surfactants, such as polyoxyethylene types, polyhydric alcohol ester types, ethyleneoxide propyleneoxide block polymers, etc. Any high molecular weight surfactants or natural surfactants can also be used without limitation. Examples of preservatives include ethyl p-hydroxybenzoate, salicylic acid, sorbic acid, etc. Examples of thickeners include xanthane gum, carboxymethyl cellulose sodium, carboxy vinyl polymers, etc. Examples of sequestering agents include sodium salts of ethylenediamine tetra-acetic acid, phosphoric acid, citric acid, etc. The composition for preventing or improving skin pigmentation can be directly applied to or sprayed onto the skin in accordance with the form. The amount in a single dose and the number of doses per day of the composition for preventing or improving skin pigmentation are determined according to the age of the user (human) , the gender, the intended use, the condition of the affected part of the skin, etc. For example, a suitable amount of the composition can be applied to the skin from once to 5 or 6 times per day. The composition for preventing or improving skin pigmentation can prevent or improve pigmentation of the skin, and therefore is useful as a skin-lightening composition, skin anti-aging composition, skin-dullness improving composition, or melasma improving composition. 2. Method for preventing or improving pigmentation The invention also provides a method for preventing or improving pigmentation of the skin. More specifically, the method comprises applying, to the human skin, at least one member (A) selected from the group consisting of adenosine 5'-monophosphates and salts thereof, and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones. In the method of the invention, the kinds of ingredient (s) (A), the kinds of ingredients (B) , and the ratio of the ingredients (A) to (B) are as mentioned above. The manner of applying the ingredients (A) and (B) to the skin and the number of times the ingredients (A) and (B) are applied per day are also as mentioned above. The amounts of the ingredients (A) and (B) applied to the skin may be adjusted to reach the effective amounts for enhancing the action of preventing or improving skin pigmentation by the combined used of the ingredients (A) and (B) . The method is suitably carried out by applying, to the skin, the effective amount of the above-mentioned composition for preventing or improving skin pigmentation. The method is useful not only as a medical method but also as a cosmetic method. The method can effectively prevent or improve pigmentation of the skin, and therefore is useful as skin-lightening methods, skin anti-aging methods, skin-dullness improving methods, or melasma improving methods. EXAMPLES The present invention is described with reference to Examples and Test Examples, but is not limited thereto. In the following Examples and Test Examples, "chamomile liquid" (liquid, 0.9% by weight of solid content, manufactured by ICHIMARU PHARCOS CO.,LTD) was used as chamomile extract. The amount of chamomile extract refers to the amount of "chamomile liquid". Example 1 Lotion AMP Arbutin 1,3-butylene glycol Concentrated glycerin Polyoxyethylenemethyl polysiloxane copolymer Ethanol Preservative pH adjuster Purified water Total (% by weight) 2.0 3.0 2.0 2.0 0.3 5.0 Suitable amount Adjusted to pH 6.5 Remainder 100.0 Example 2 Lotion AMP Tranexamic acid Dipropylene glycol Concentrated glycerin Polyoxyethylene sorbitan monostearate (20E.O.) Ethanol Preservative pH adjuster Perfume Purified water Total (% by weight) 2. 3. 3. 2. 1.0 10.0 Suitable amount Adjusted to pH 6.5 Suitable amount Remainder 100.0 Example 3 Cream AMP Ellagic acid Polyoxyethylene alkylene alkyl-comodified silicone Decamethylcyclopentasiloxane Liquid paraffin Concentrated glycerin 1,3-butylene glycol Ethanol Preservative pH adjuster Purified water Total (% by weight) 2.0 0.5 2.0 18.0 4.0 3.0 3.0 5.0 Suitable amount Adjusted to pH 6.5 Remainder 100.0 Example 4 Treatment lotion AMP2Na Chamomile extract (trade name: "chamomile liquid", manufactured by ICHIMARU PHARCOS CO.,LTD) Dipropylene glycol Concentrated glycerin Sodium hyaluronate Xanthan gum Polyoxyethylenemethyl polysiloxane copolymer Ethanol Preservative pH adjuster Perfume Purified water Total (% by weight) 1.5 5.0 3. 3. 0. 0. 0. 3.0 Suitable amount Adjusted to pH 6.5 Suitable amount Remainder ___ 100.0 Example 5 Milky lotion AMP2Na 4-hexylresorcinol Ascorbyl tetra 2-hexyldecanate Polyoxyalkylene alkyl-comodified silicone Decaglycerol monostearate Glycerol monostearate Stearic acid Behenyl alcohol Tri-2-ethyl hexane acid glycerol Squalan Decamethylcyclopentasiloxane Hydrogenated soybean phosphatide dl-a-tocopherol acetate Concentrated glycerin 1,3-butylene glycol Carboxyvinyl polymer Preservative pH adjuster Purified water Total (% by weight) 1.0 0.5 2.0 .0 .0 .0 ,0 .0 ,0 ,0 1.0 0. 0. 3. 3. 0.3 Suitable amount Adjusted to pH 6.5 Remainder 100.0 Example 6 Lotion AMP2Na Linolic acid Hydrogenated soybean phosphatide Dipropylene glycol Ethanol Preservative pH adjuster Purified water Total (% by weight) 1.5 0.1 1.0 5.0 3.0 Suitable amount Adjusted to pH 6.5 Remainder 100.0 Example 7 Cream AMP2Na Linolic acid Stearic acid Polyethylene glycol monostearate (40E.O.) Self-emulsifying glycerol monostearate Tri-2-ethyl-hexanoic-acid glycerol Behenyl alcohol Squalane Concentrated glycerin Preservative pH adjuster Perfume Purified water Total (% by weight) 1.5 2. 3, 2. 5.0 15.0 1.0 10.0 5.0 Suitable amount Adjusted to pH 6.5 Suitable amount Remainder 100.0 Example 8 Cream Coenzyme Q10 Polyoxyethylene sorbitan monostearate Propylene glycol monostearate Glycerol monostearate Paraffin wax Behenyl alcohol White petrolatum Liquid paraffin Squalane Cetyl Isooctanate Silicone oil 1,3-butylene glycol Preservative Perfume Purified water Total (% by weight) 0.03 3.0 4.5 3.5 0.8 3.5 3.0 10.0 3.0 10.0 0.2 7.0 Suitable amount Suitable amount Remainder 100.0 Test Example 1: Evaluation of the pigmentation improvement effect-1 The following tests were performed using colored guinea pigs for evaluating the pigmentation improving effect obtained by the combined use of AMP and arbutin. Preparation of a sample and production of an animal model> 1. Preparation of a test solution Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 3% by weight arbutin (\|3 type) (Formulation Example 1), a solution comprising a 3% by weight AMP2Na (Comparative Formulation Example 1-1), and a solution comprising 3% by weight arbutin ((3 type) (Comparative Formulation Example 1-2) were prepared. 2. Production of an animal model with skin pigmentation The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal. 11 days after the final ultraviolet irradiation exposure for the guinea pigs, one of each test solution was applied twice per day for 14 days. Each of the four pigmentation sites of each colored guinea pig was applied with a suitable amount of one solution, from among the three test solutions (Formulation Example 1, and Comparative Formulation Examples 1-1 and 1-2) and a 20% by weight ethanol aqueous solution (control). Fourteen days later, 5 judgment persons compared the skin brightness between each pigmentation site, to which one solution, from among the three test solutions was applied and the site to which the control was applied, according to t Scheffe's paired comparison method, and graded the comparison results in accordance with the judgment criteria shown in Table 1. Table 1 (Table Removed) Before the application and 14 days after the application, 5 judgment persons compared the three pigmentation sites of the guinea pigs, each of which was applied with one solution, from among the three test solutions, with the pigmentation site to which' the control was applied and graded the comparison. The total of the visual grading scores for each pigmentation site obtained from each of the five judgment persons was defined as the visual grading scores for each test solution. The average visual grading scores for each test solution was calculated from eight colored guinea pigs. The delta value (A) of visual grading score was calculated by subtracting the visual grading scores before the application of the test solution from the visual grading scores 14 days after the application. A higher calculated delta value (A) of visual grading score shows that the skin color of the pigmentation site to which the test solution was applied was lighter than that of the pigmentation site to which the base agent was applied, and a higher delta value (A) of visual grading score shows that the pigmentation improvement effect is high. The obtained results are shown in Figure 1, in which the delta values (A) of visual grading scores that were obtained by subtracting the visual grading scores before the application of the test solution from the visual grading scores 14 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 1-1 and 1-2 were 1.00 and 0.50, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 1 was 5.50. The fact that the sum of the delta values (A) of visual grading scores of Comparative Formulation Examples 1-1 and 1-2 was 1.50 and the delta value (A) of visual grading score of Formulation Example 1 was 5.50 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and arbutin in Formulation Example 1. Test Example 2: Evaluation of the pigmentation improvement effect-2 1. Preparation of a test solution Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 0.5% by weight ellagic acid hydrate (Formulation Example 2), a solution comprising 3% by weight AMP2Na (Comparative Formulation Example 2-1), and a solution comprising 0.5% by weight ellagic acid hydrate (Comparative Formulation Example 2-2) were prepared. 2. Production of an animal model with pigmentation The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal. The experiment was performed using the eight colored guinea pigs, following the procedure of Test Example 1, except that the test solution was applied twice per day for 28 days. The delta value (A) of visual grading score was calculated in the same manner as in Test Example 1 above. The obtained results are shown in Figure 2, in which the delta values (A) of visual grading scores that were obtained by subtracting the visual comparison grade before the application of the test solution from the visual grading scores 28 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 2-1 and 2-2 were 1.25 and 3.25, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 2 was 10.50. The fact that the sum of the delta values (A) of visual grading scores of Comparative Formulation Examples 2-1 and 2-2 was 4.50 and the delta value (A) of visual grading score of Formulation Example 2 was 10.50 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and ellagic acid hydrate in Formulation Example 2. Test Example 3: Evaluation of the pigmentation improvement effect-3 The following test was performed using colored guinea pigs for evaluating the effect of improving pigmentation obtained by the combined use of AMP and tranexamic acid. 1. Preparation of a test solution Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 3% by weight tranexamic acid (Formulation Example 3), a solution comprising 3% by weight AMP2Na (Comparative Formulation Example 3-1), and a solution comprising 3% by weight tranexamic acid (Comparative Formulation Example 2-2) were prepared. 2. Production of an animal model with pigmentation The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal. Following the procedure of Test Example 1, the test was performed using the eight colored guinea pigs. The delta value (A) of visual grading score was calculated in the same manner as in Test Example 1 above. The obtained results are shown in Figure 3, in which the delta values (A) of visual grading scores that were obtained by subtracting the visual grading scores before the application of the test solution from the visual grading scores 14 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 3-1 and 3-2 were 1.75 and 1.25, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 3 was 4.50. The fact that the sum of the delta values (A) of visual grading scores of Comparative Formulation Examples 3-1 and 3-2 was 3.00 and the delta value (A) of visual grading scores of Formulation Example 3 was 4.50 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and tranexamic acid in Formulation Example 3. Test Example 4: Evaluation of the pigmentation improvement effect-4 1. Preparation of a test solution Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 0.3% by weight 4-n-hexylresorcinol (Formulation Example 4), a solution comprising 3% by weight AMP2Na (Comparative Formulation Example 4-1), and a solution comprising 0.3% by weight 4-n-hexylresorcinol (Comparative Formulation Example 4-2) were prepared. 2. Production of an animal model with pigmentation The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal. Following the procedure of Comparative Test Example 1, the test was performed and the delta value (A) of visual grading score was calculated. The obtained results are shown in Figure 4, in which the delta values (A) of visual grading scores that were obtained by subtracting the visual grading scores before the application of the test solution from the visual comparison grade 14 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 4-1 and 4-2 were 1.25 and 1.75, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 4 was 7.25. The fact that the sum of the delta values (A) of visual grading scores of Comparative Formulation Examples 4-1 and 4-2 was 3.00 and the delta value (A) of visual grading score of Formulation Example 4 was 7.25 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and 4-n-hexylresorcinol in Formulation Example 4. Test Example 5: Evaluation of the pigmentation improvement effect-5 1. Preparation of a test solution Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 5% by weight chamomile extract (trade name "chamomile liquid", manufactured by ICHIMARU PHARCOS CO., LTD) (Formulation Example 5), a solution comprising 3% by weight AMP2Na (Comparative Formulation Example 5-1), and a solution comprising 5% by weight chamomile extract (Comparative Formulation Example 5-2) were prepared. 2. Production of an animal model with pigmentation The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal. Following the procedure of Comparative Test Example 1, the test was performed and the delta value (A) of visual grading score was calculated. The obtained results are shown in Figure 5, in which the delta values (A) of visual grading scores that were obtained by subtracting the visual grading scores before the application of the test solution from the visual grading scores 14 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 5-1 and 5-2 were 1.13 and 0.50, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 5 was 3.00. The fact that the sum of the delta values (A) of visual grading scores of Comparative Formulation Examples 5-1 and 5-2 was 1.63 and the delta value (A) of visual grading score of Formulation Example 5 was 3.00 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and 4-n-hexylresorcinol. Test Example 6: Evaluation of the pigmentation improvement effect-6 1. Preparation of a test solution Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 1% by weight coenzyme Q10 (Formulation Example 6), a solution comprising 3% by weight AMP2Na (Comparative Formulation Example 6-1), and a solution comprising 1% by weight coenzyme Q10 (Comparative Formulation Example 6-2) were prepared. 2. Production of an animal model with pigmentation The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal. Following the procedure of Comparative Test Example 1, the test was performed and the delta value (A) of visual grading score was calculated. The obtained results are shown in Figure 6, in which the delta values (A) of visual grading scores that were obtained by subtracting the visual comparison grade before the application of the test solution from the visual grading scores 14 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 6-1 and 6-2 were 1.25 and 0.63, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 6 was 3.88. The fact that the sum of the delta values (A) of visual grading scores of Comparative Formulation Examples 6-1 and 6-2 was 1.88 and the delta value (A) of visual grading score of Formulation Example 6 was 3.88 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na coenzyme Q10. Test Example 7; Evaluation of the pigmentation improvement effect-7 Using linolic acid in place of arbutin, the same test as described in Test Example 1 is performed, and the test confirms that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and linolic acid in the same manner as shown in the results of Test Example 1. INDUSTRIAL APPLICABILITY The composition for preventing or improving skin pigmentation of the invention comprises AMP or a salt thereof as an ingredient (A) and a specific melanin formation inhibitor or ubiquinone as an ingredient (B) in combination, and therefore the actions of preventing or improving skin pigmentation of both ingredients (A) and (B) are synergistically enhanced. Thus, since the composition for preventing or improving skin pigmentation of the invention exhibits a superior skin pigmentation prevention or improvement effect, the composition of the invention is useful as a cosmetics and externally-applied preparation for the skin (pharmaceutical composition) for the purpose of skin-lightening, skin anti-aging, reduction of skin dullness, and amelioration of melanoma. The ingredients (A) and (B) used as an active ingredient in the composition for preventing or improving skin pigmentation of the invention are confirmed to be highly safe, and thus can be used daily as a cosmetic material. Therefore, users can prevent or improve skin pigmentation simply and easily by the daily use, as cosmetics, of the composition for preventing or improving pigmentation of the invention. WE CLAIM 1. A composition for preventing or improving pigmentation, the composition comprising: at least one member (A) selected from the group consisting of adenosine 5'- monophosphates and salts thereof; and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4- alkylresorcinols, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones wherein the composition comprises said at least one member (A) in a total proportion of 0.05 to 10% by weight based on a total weight of the composition, and, said at least one member (B)) in a total proportion of 0.0001 to 50% by weight based on a total weight of the composition. 2. The composition as claimed in claim 1, as and when used as a cosmetic or pharmaceutical composition for preventing or improving pigmentation.

Full Text

DESCRIPTION COMPOSITION FOR PREVENTION OR ALLEVIATION OF PIGMENTATION
TECHNICAL FIELD
The present invention relates to a composition for preventing or improving pigmentation of the skin that can prevent or improve effectively skin pigmentation. The present invention also relates to a method for preventing or improving pigmentation of the skin.
BACKGROUND OF THE INVENTION
Pigmentation of the skin, such as chloasma, freckles, and the like, is a serious aesthetic problem particularly for women. Generally, the onset of chloasma and freckles on the skin is induced by the precipitation of melanin pigment formed in the skin cells when the skin is stimulated by exposure to ultraviolet light and the like. Therefore, pigmentation of the skin, such as chloasma, freckles, and the like, has heretofore been prevented or improved by the use of an externally-applied composition comprising arbutin, kojic acid, ascorbic acid, ascorbic acid derivatives, ellagic acid, 4-n-butylresorcinol, linolic acid, tranexamic acid, chamomile extract, etc., which directly or indirectly inhibit the formation of melanin pigment (e.g., Non-patent Document 1). However, these externally-applied compositions are disadvantageous in that the effect of improving the pigmentation is slow and insufficient. Ubiquinone is known to have an antioxidant action, but the effect of preventing or improving pigmentation is inadequate and is not satisfactory.
In contrast, Adenosine 5'-monophosphate (hereinafter referred to as AMP) is already known to have an action for improving the pigmentation of the skin, and can be suitably used in externally-applied compositions for improving the pigmentation of the skin.
However, no case to date has been reported in which a specific melanin formation inhibitor or ubiquinone is used in combination with AMP until now, and thus the effect obtained by the combined use thereof is not known.
[Non-patent Document 1]
"Keshohin no Yuyosei: Hyokagijutu no Shinpo to Shorai Tenbo"
(Functional Cosmetology Substantiation of Cosmetics Efficacy: Recent Progress and Future Promise of Evaluation Techniques); edited by Katsuiyuki TAKEDA, Shotaro HARADA, and Masanori ANDO; Nippon Keshohin Gijutsushakai;Yakuji Nippo; pp. 149 to 159.
DISCLOSURE OF THE INVENTION PROBLEM TO BE SOLVED BY THE INVENTION
The present invention aims to provide a composition for preventing or improving pigmentation of the skin that can effectively prevent or improve the skin pigmentation. The present invention also aims to provide a method for effectively preventing or improving pigmentation of the skin.
MEANS FOR SOLVING THE PROBLEM
The present inventors carried out extensive research to solve the above-described problems, and found that the action of preventing or improving pigmentation of the skin is synergistically enhanced by the combined use of at least one member (A) selected from the group consisting of AMP and salts thereof; and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones. The inventors conducted further research and accomplished the present invention based on these findings.
More specifically, the present invention encompasses the following aspects.

Item 1. A composition for preventing or improving pigmentation, the composition comprising:
at least one member (A) selected from the group consisting of adenosine 5'-monophosphates and salts thereof; and
at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones.
Item 2. A composition according to item 1, comprising said at least one member (A) in a total proportion of 0.05 to 10% by weight based on a total weight of the composition. Item 3. A composition according to item 1, comprising said at least one member (B) in a total proportion of 0.00001 to 100 parts by weight per part by weight of a total weight of said at least one member (A) .
Item 4. A composition according to item 1, comprising said at least one member (B) in a total proportion of 0.0001 to 50% by weight based on a total weight of the composition. Item 5. A composition according to item 1, wherein said at least one member (B) is selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, and salts thereof, and said at least one member (B) is contained in a total proportion of 0.1 to 100 parts by weight per part by weight of a total weight of said at least one member (A).
Item 6. A composition according to item 1, wherein said at least one member (B) is selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, and salts thereof, and said at least one member (B) is contained in a total proportion of 0.01 to 50% by weight based on a total weight of the composition. Item 7. A composition according to item 1, wherein said at least one member (B) is chamomile extract, and said at least one member (B) is contained in a total proportion of

preferably 0.00001 to 10 parts by weight as calculated in terms of solid content per part by weight of a total weight of said at least one member (A).
Item 8. A composition according to item 1, wherein said at least one member (B) is chamomile extract, and said at least one member (B) is contained in a total proportion of 0.0001 to 0.5% by weight as calculated in terms of solid content. Item 9. A composition according to item 1, wherein said at least one member (B) is ubiquinone, and said at least one member (B) is contained in a total proportion of 0.001 to 100 parts by weight per part by weight of a total weight of said at least one member (A).
Item 10. A composition according to item 1, wherein said at least one member (B) is ubiquinone, and said at least one member (B) is contained in a total proportion of 0.0001 to 50% by weight based on a total weight of the composition. Item 11. A composition according to item 1, being a cosmetic composition or a pharmaceutical composition.
Item 12. A method for preventing or improving pigmentation, comprising applying, to human skin, at least one member (A) selected from the group consisting of adenosine 5'-monophosphates and salts thereof and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones. Item 13. A method according to item 12, comprising applying, to human skin, a composition of any one of items 1 to 11. Item 14. A method according to item 12, being a cosmetic method.
Item 15. Use of at least one member (A) selected from the group consisting of adenosine 5'-monophosphate and salts thereof and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones for the production of a composition
for preventing or improving skin pigmentation.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 shows delta values (A) of visual grading scores (indexes showing the improvement effects of skin pigmentation) of Formulation Example 1 (combined use of AMP2Na and arbutin), Comparative Formulation Example 1-1 (AMP2Na), and Comparative Formulation Example 1-2 (arbutin) in Test Example 1.
Fig. 2 shows delta values (A) of visual grading scores
(indexes showing the improvement effects of skin
pigmentation) of Formulation Example 2 (combined use of
AMP2Na and ellagic acid hydrate), Comparative Formulation
Example 2-1 (AMP2Na), and Comparative Formulation Example 2-2
(ellagic acid hydrate) in Test Example 2.
Fig. 3 shows delta values (A) of visual grading scores
(indexes showing the improvement effects of skin
pigmentation) of Formulation Example 3(combined use of AMP2Na
and tranexamic acid), Comparative Formulation Example 3-1
(AMP2Na) and Comparative Formulation Example 3-2 (tranexamic
acid) in Test Example 3.
Fig. 4 shows delta values (A) of visual grading scores
(indexes showing the improvement effects of skin
pigmentation) of Formulation Example 4 (combined use of
AMP2Na and 4-n-hexylresorcinol) , Comparative Formulation
Example 4-1 (AMP2Na) and Comparative Formulation Example 4-2
(4-n-hexylresorcinol) in Test Example 4.
Fig. 5 shows delta values (A) of visual grading scores
(indexes showing the improvement effects of skin
pigmentation) of Formulation Example 5 (combined use of
AMP2Na and chamomile extract), Comparative Formulation
Example 5-1 (AMP2Na) and Comparative Formulation Example 5-2
(chamomile extract) in Test Example 5.
Fig. 6 shows delta values (A) of visual grading scores (indexes showing the improvement effects of skin

pigmentation) of Formulation Example 6 (combined use of AMP2Na and coenzyme Q10), Comparative Formulation Example 6-1 (AMP2Na) and Comparative Formulation Example 6-2 (coenzyme Q10) in Test Example 6.
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the present invention will be described in detail. 1. Composition for preventing or improving skin pigmentation
The composition for preventing or improving skin pigmentation of the invention comprises at least one member (hereinafter referred to as ingredient(s) (A)) selected from the group consisting of AMP and salts thereof.
In the invention, there is no limitation on the salts of AMP used as the ingredient (s) (A) insofar as they can be added to cosmetics and externally-applied pharmaceutical compositions. Specific examples of the salts of AMP include alkali metal salts such as sodium salts, potassium salts, and the like; alkaline earth metal salts such as calcium salts, magnesium salts, barium salts, and the like; basic amino acid salts, such as arginine, lysine, and the like; ammonium salts, such as ammonium salts, tricyclohexyl ammonium salts, and the like; various alkanolamine salts such as monoethanolamine salts, diethanolamine salts, triethanolamine salts, monoisopropanolamine salts, diisopropanolamine salts, and triisopropanolamine, and the like. Among these, alkali metal salts, such as sodium salts and the like, are preferable. Specific examples of such alkali metal salts include adenosine monophosphate monosodium and adenosine monophosphate disodium. These salts of AMP may be used singly or in combination.
The proportion of the ingredient (s) (A) added to the composition of the invention is not limited and can be suitably adjusted according to the form of the composition, kind of the ingredient (s) (A), expected effect, etc. As one
example, the total proportion of the ingredient (s) (A) is in the range of 0.05 to 10% by weight, preferably 0.1 to 7% by weight, and more preferably 0.5 to 6% by weight based on the total weight of the composition for preventing or improving skin pigmentation.
The composition for preventing or improving skin
pigmentation of the invention comprises at least one member
(hereinafter referred to as ingredient(s) (B)) selected from
the group consisting of arbutins (chemical name: 4-
hydroxyphenyl-p-D-glucopyranoside and 4-Hydroxyphenyl-oc-D-glucopyranoside), ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones in addition to the ingredient(s) (A).
The above-mentioned arbutin may be either a- or P-arbutin.
Specific examples of the above-mentioned 4-alkylresorcinol include 4-methylresorcinol, 4-ethylresorcinol, 4-n-propylresorcinol, 4-n-butylresorcinol, 4-n-pentylresorcinol, 4-n-hexylresorcinol, etc. Among these, 4-n-butylresorcinol, 4-n-pentylresorcinol, and 4-n-hexylresorcinol are preferable, and 4-n-butylresorcinol and 4-n-hexylresorcinol are more preferable.
Among the above-mentioned ingredients (B), arbutin, ellagic acid, 4-alkylresorcinol, linolic acid, and tranexamic acid may be in the form of a salt insofar as they are cosmetically or pharmaceutically acceptable. Examples of these salts include alkali metal salts, alkaline earth metal salts, basic amino acid salts, ammonium salts, alkanolamine salts, etc. as well as above-mentioned examples of the salts of AMP.
Chamomile extracts are extracts obtained by extracting flower and/or stem of Matricaria chamomilla using a solvent. Specifically, chamomile extracts can be obtained by extracting from the flower and/or stem of Matricaria chamomilla in water or an organic solvent, or a mixed liquid
of water and an organic solvent at normal temperature or under warmed conditions. The flower and/or stem may be used as it is, or, as required, may be dried, chopped, crushed, compressed, or boiled for the extraction step. Examples of the organic solvent used for this extraction process include lower alcohols with a carbon number range of C1-C5 (e.g., methanol, ethanol, propanol, isopropanol, butanol, etc.), propylene glycol, 1,3-butylene glycol, acetone, ethyl acetate, chloroform, toluene, pentane, hexane, heptane, etc. and these solvents can be used singly or in combination. As the extracting solvent, water, lower alcohols with a carbon number range of C1-C5, or a mixture of such alcohols and water is preferable, and ethanol and the mixture of ethanol and water are particularly preferable. In the case of the mixture of lower alcohols with a carbon number range of C1-C5 and water, the proportion of the alcohol based on the total weight of the mixture is, for example, 0.01 to 100% by weight, preferably 5 to 55% by weight, and more preferably 45 to 55% by weight. Chamomile extracts are commercially available, and such commercially-available chamomile extracts can be used.
In the invention, chamomile extracts may be used in the form of an extracted liquid, an extracted concentrate, purified matter, dried matter, a solution made using dried matter, or fractioned matter, etc.
There is no limitation on the above-mentioned ubiquinones, and, for example, coenzyme Q6, coenzyme Q7, coenzyme Q8, coenzyme Q9, and coenzyme Q10 can be mentioned. Among these, coenzyme Q10 is preferable.
The proportion of the ingredient (s) (B) added to the composition of the invention is not limited and can be suitably adjusted according to the form of the composition, the expected effect, and the like. As one example, the total proportion of the ingredient (s) (B) is in the range of 0.00001 to 100 parts by weight per part by weight of the
total weight of ingredient(s) (A). More specifically, when the ingredient(s) (B) is arbutin, ellagic acid, 4-alkylresorcinol, linolic acid, tranexamic acid, and/or salts thereof, the total proportion of the ingredient (s) (B) is preferably 0.1 to 100 parts by weight, and more preferably 1 to 100 parts by weight, per part by weight of the total weight of ingredient(s) (A). For example, when the ingredient (s) (B) is chamomile extract, the total proportion of the ingredient(s) (B) is preferably 0.00001 to 10 parts by weight, and more preferably 0.0001 to 10 parts by weight, per part by weight of the total weight of ingredient (s) (A). As another example, when the ingredient(s) (B) is ubiquinone, the total proportion of the ingredient(s) (B) is preferably 0.001 to 100 parts by weight, and more preferably 0.01 to 100 parts by weight, per part by weight of a total weight of ingredient(s) (A). In the above-mentioned proportions of the ingredient (s) (B) , the proportion of chamomile extract is calculated in terms of solid content. With the combined use of the ingredients (A) and (B) in the above-mentioned proportions, the effects of preventing or improving skin pigmentation of both the ingredients (A) and (B) are synergistically enhanced, whereby more excellent pigmentation inhibitory effects are exhibited.
The total proportion of ingredient(s) (B) is, for example, 0.0001 to 50% by weight based on the total weight of the composition for preventing or improving skin pigmentation. More specifically, when the ingredient(s) (B) is arbutin, ellagic acid, 4-alkylresorcinol, linolic acid, tranexamic acid, and/or salts thereof, the total proportion of the ingredient (s) (B) is, for example, 0.01 to 50% by weight, preferably 0.05 to 30% by weight, and more preferably 0.1 to 20% by weight. When the ingredient (s) (B) is chamomile extract, the total proportion of the ingredient (s) (B) is, for example, 0.0001 to 0.5% by weight, preferably 0.0005 to 0.3% by weight, and more preferably 0.001 to 0.2% by weight.
When the ingredient (s) (B) is ubiquinone, the total proportion of the ingredient (s) (B) is, for example, 0.0001 to 50% by weight, preferably 0.001 to 30% by weight, and more preferably 0.01 to 20% by weight. In the above-mentioned proportions of the ingredient (s) (B), the proportion of chamomile extract is calculated in terms of solid content.
The composition for preventing or improving skin pigmentation of the invention is formed into cosmetic compositions, externally-applied pharmaceutical compositions, and the like so that it is applied through the skin. In the invention, the externally-applied pharmaceutical compositions encompass externally-applied medical or quasi-medical drugs. Such externally-applied pharmaceutical compositions for preventing or improving skin pigmentation can take any form without limitation insofar as they are applicable to the skin or mucosa, such as an aqueous solution, a solubilized form, an emulsified form, a dispersed powder, a water/oil two-layer type, etc. Specific examples include solutions, oily preparations, lotions, liniments, emulsions, suspensions, creams, ointments, etc. Examples of cosmetic compositions include lotions; emollient emulsions, milky lotions, nourishing emulsions, cleansing emulsions, and like emulsions; emollient creams, massage creams, cleansing creams, makeup creams, and like creams; etc. The composition for preventing or improving pigmentation of the invention may also be formed into hair care products such as hair growth formula and the like. Examples of hair care products include hair tonics, hair creams, hair lotions, aerosols (air sprays), mousses, shampoos, rinses, liquids, etc.
The composition for preventing or improving skin pigmentation of the invention may contain a wide range of known components added to-compositions applied to the skin or mucosa, such as cosmetic compositions, externally-applied pharmaceutical compositions, and the like. Examples of such ingredients include humectants, UV absorbers, UV dispersants,
vitamins, plant extracts, astringents, anti-inflammatory agents (antiphlogistic agents), whiteners, cell activators, vasodilators, blood circulation accelerators, skin function accelerators, and the like in addition to surfactants, coloring agents (dyes, pigments), perfumes, preservatives, bactericides (antibacterials), thickeners, antioxidants, sequestering agents, refrigerants, deodorizers, and the like. Known bases or carriers can also be used in accordance with the above-mentioned various forms.
Among the above-mentioned ingredients, examples of surfactants include anionic surfactants, such as salts of higher fatty acids, alkylsulfonates, polyoxyethylene alkyl ether sulfates, alkyl ether phosphates, W-acylamino acid salts, acyl W-methyltaurates, etc.; cationic surfactants, such as alkyltrimethyl ammonium chlorides, dialkyldimethyl ammonium chlorides, etc.; amphoteric surfactants, such as alkyl dimethylaminoacetic acid betaines,
alkylamidodimethylaminoacetate betaines, 2-alkyl-N-carboxy-W-hydroxyimidazolinium betaines, etc.; nonionic surfactants, such as polyoxyethylene types, polyhydric alcohol ester types, ethyleneoxide propyleneoxide block polymers, etc. Any high molecular weight surfactants or natural surfactants can also be used without limitation.
Examples of preservatives include ethyl p-hydroxybenzoate, salicylic acid, sorbic acid, etc. Examples of thickeners include xanthane gum, carboxymethyl cellulose sodium, carboxy vinyl polymers, etc. Examples of sequestering agents include sodium salts of ethylenediamine tetra-acetic acid, phosphoric acid, citric acid, etc.
The composition for preventing or improving skin pigmentation can be directly applied to or sprayed onto the skin in accordance with the form. The amount in a single dose and the number of doses per day of the composition for preventing or improving skin pigmentation are determined according to the age of the user (human) , the gender, the
intended use, the condition of the affected part of the skin, etc. For example, a suitable amount of the composition can be applied to the skin from once to 5 or 6 times per day.
The composition for preventing or improving skin pigmentation can prevent or improve pigmentation of the skin, and therefore is useful as a skin-lightening composition, skin anti-aging composition, skin-dullness improving composition, or melasma improving composition.
2. Method for preventing or improving pigmentation
The invention also provides a method for preventing or improving pigmentation of the skin. More specifically, the method comprises applying, to the human skin, at least one member (A) selected from the group consisting of adenosine 5'-monophosphates and salts thereof, and at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-alkylresorcinols, linolic acid, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones.
In the method of the invention, the kinds of ingredient (s) (A), the kinds of ingredients (B) , and the ratio of the ingredients (A) to (B) are as mentioned above. The manner of applying the ingredients (A) and (B) to the skin and the number of times the ingredients (A) and (B) are applied per day are also as mentioned above.
The amounts of the ingredients (A) and (B) applied to
the skin may be adjusted to reach the effective amounts for
enhancing the action of preventing or improving skin
pigmentation by the combined used of the ingredients (A) and
(B) .
The method is suitably carried out by applying, to the skin, the effective amount of the above-mentioned composition for preventing or improving skin pigmentation.
The method is useful not only as a medical method but also as a cosmetic method. The method can effectively prevent or improve pigmentation of the skin, and therefore is
useful as skin-lightening methods, skin anti-aging methods, skin-dullness improving methods, or melasma improving methods.
EXAMPLES
The present invention is described with reference to Examples and Test Examples, but is not limited thereto. In the following Examples and Test Examples, "chamomile liquid" (liquid, 0.9% by weight of solid content, manufactured by ICHIMARU PHARCOS CO.,LTD) was used as chamomile extract. The amount of chamomile extract refers to the amount of "chamomile liquid".

Example 1 Lotion
AMP
Arbutin
1,3-butylene glycol
Concentrated glycerin
Polyoxyethylenemethyl polysiloxane copolymer
Ethanol
Preservative
pH adjuster
Purified water
Total

(% by weight) 2.0 3.0 2.0 2.0 0.3 5.0
Suitable amount Adjusted to pH 6.5 Remainder
100.0

Example 2 Lotion
AMP
Tranexamic acid
Dipropylene glycol
Concentrated glycerin
Polyoxyethylene sorbitan monostearate (20E.O.)
Ethanol
Preservative
pH adjuster
Perfume
Purified water
Total

(% by weight)
2. 3. 3. 2.
1.0
10.0
Suitable amount
Adjusted to pH 6.5
Suitable amount
Remainder
100.0

Example 3 Cream
AMP
Ellagic acid
Polyoxyethylene alkylene alkyl-comodified silicone
Decamethylcyclopentasiloxane
Liquid paraffin
Concentrated glycerin
1,3-butylene glycol
Ethanol
Preservative
pH adjuster
Purified water
Total

(% by weight) 2.0 0.5 2.0 18.0 4.0 3.0 3.0 5.0
Suitable amount Adjusted to pH 6.5 Remainder
100.0

Example 4 Treatment lotion
AMP2Na
Chamomile extract (trade name: "chamomile liquid", manufactured by ICHIMARU PHARCOS CO.,LTD) Dipropylene glycol Concentrated glycerin Sodium hyaluronate Xanthan gum
Polyoxyethylenemethyl polysiloxane copolymer Ethanol Preservative pH adjuster Perfume
Purified water
Total

(% by weight)
1.5 5.0
3. 3. 0. 0. 0.
3.0
Suitable amount Adjusted to pH 6.5 Suitable amount
Remainder ___
100.0

Example 5 Milky lotion
AMP2Na
4-hexylresorcinol
Ascorbyl tetra 2-hexyldecanate
Polyoxyalkylene alkyl-comodified silicone
Decaglycerol monostearate
Glycerol monostearate
Stearic acid
Behenyl alcohol
Tri-2-ethyl hexane acid glycerol
Squalan
Decamethylcyclopentasiloxane
Hydrogenated soybean phosphatide
dl-a-tocopherol acetate
Concentrated glycerin
1,3-butylene glycol
Carboxyvinyl polymer
Preservative
pH adjuster
Purified water
Total

(% by weight)
1.0 0.5 2.0
.0 .0 .0 ,0 .0 ,0 ,0
1.0
0. 0. 3. 3.
0.3
Suitable amount
Adjusted to pH 6.5
Remainder
100.0

Example 6 Lotion
AMP2Na
Linolic acid
Hydrogenated soybean phosphatide
Dipropylene glycol
Ethanol
Preservative
pH adjuster
Purified water
Total

(% by weight) 1.5 0.1 1.0 5.0 3.0
Suitable amount Adjusted to pH 6.5
Remainder
100.0

Example 7 Cream
AMP2Na
Linolic acid
Stearic acid
Polyethylene glycol monostearate (40E.O.)
Self-emulsifying glycerol monostearate
Tri-2-ethyl-hexanoic-acid glycerol
Behenyl alcohol
Squalane
Concentrated glycerin
Preservative
pH adjuster
Perfume
Purified water
Total

(% by weight)
1.5
2. 3, 2.
5.0
15.0
1.0
10.0
5.0
Suitable amount
Adjusted to pH 6.5
Suitable amount
Remainder
100.0

Example 8 Cream
Coenzyme Q10
Polyoxyethylene sorbitan monostearate
Propylene glycol monostearate
Glycerol monostearate
Paraffin wax
Behenyl alcohol
White petrolatum
Liquid paraffin
Squalane
Cetyl Isooctanate
Silicone oil
1,3-butylene glycol
Preservative
Perfume
Purified water
Total

(% by weight)
0.03
3.0
4.5
3.5
0.8
3.5
3.0
10.0
3.0
10.0
0.2
7.0
Suitable amount
Suitable amount
Remainder
100.0

Test Example 1: Evaluation of the pigmentation improvement effect-1
The following tests were performed using colored guinea pigs for evaluating the pigmentation improving effect obtained by the combined use of AMP and arbutin. Preparation of a sample and production of an animal model> 1. Preparation of a test solution
Using a 20% by weight ethanol aqueous solution as a

base material, a mixed solution of 3% by weight AMP2Na and 3%
by weight arbutin (|3 type) (Formulation Example 1), a
solution comprising a 3% by weight AMP2Na (Comparative
Formulation Example 1-1), and a solution comprising 3% by
weight arbutin ((3 type) (Comparative Formulation Example 1-2) were prepared.
2. Production of an animal model with skin pigmentation
The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal.

11 days after the final ultraviolet irradiation exposure for the guinea pigs, one of each test solution was applied twice per day for 14 days. Each of the four pigmentation sites of each colored guinea pig was applied with a suitable amount of one solution, from among the three test solutions (Formulation Example 1, and Comparative Formulation Examples 1-1 and 1-2) and a 20% by weight ethanol aqueous solution (control). Fourteen days later, 5 judgment persons compared the skin brightness between each pigmentation site, to which one solution, from among the three test solutions was applied and the site to which the control was applied, according to t Scheffe's paired comparison method, and graded the comparison results in accordance with the judgment criteria shown in Table 1. Table 1

(Table Removed)
Before the application and 14 days after the application, 5 judgment persons compared the three pigmentation sites of the guinea pigs, each of which was applied with one solution, from among the three test solutions, with the pigmentation site to which' the control was applied and graded the comparison. The total of the visual grading scores for each pigmentation site obtained from each of the five judgment persons was defined as the visual grading scores for each test solution. The average visual grading scores for each test solution was calculated from eight colored guinea pigs. The delta value (A) of visual grading score was calculated by subtracting the visual grading scores before the application of the test solution from the visual grading scores 14 days after the application.
A higher calculated delta value (A) of visual grading score shows that the skin color of the pigmentation site to which the test solution was applied was lighter than that of the pigmentation site to which the base agent was applied, and a higher delta value (A) of visual grading score shows that the pigmentation improvement effect is high.

The obtained results are shown in Figure 1, in which
the delta values (A) of visual grading scores that were obtained by subtracting the visual grading scores before the application of the test solution from the visual grading scores 14 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 1-1 and 1-2 were 1.00 and 0.50, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 1 was 5.50. The fact that the sum of the delta values (A) of visual grading scores of Comparative Formulation Examples 1-1 and 1-2 was 1.50 and the delta value (A) of visual grading score of Formulation Example 1 was 5.50 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and arbutin in Formulation Example 1.
Test Example 2: Evaluation of the pigmentation improvement
effect-2

1. Preparation of a test solution
Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 0.5% by weight ellagic acid hydrate (Formulation Example 2), a solution comprising 3% by weight AMP2Na (Comparative Formulation Example 2-1), and a solution comprising 0.5% by weight ellagic acid hydrate (Comparative Formulation Example 2-2) were prepared.
2. Production of an animal model with pigmentation
The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal.

The experiment was performed using the eight colored
guinea pigs, following the procedure of Test Example 1, except that the test solution was applied twice per day for 28 days.

The delta value (A) of visual grading score was calculated in the same manner as in Test Example 1 above.

The obtained results are shown in Figure 2, in which the delta values (A) of visual grading scores that were obtained by subtracting the visual comparison grade before the application of the test solution from the visual grading scores 28 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 2-1 and 2-2 were 1.25 and 3.25, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 2 was 10.50. The fact that the sum of
the delta values (A) of visual grading scores of Comparative Formulation Examples 2-1 and 2-2 was 4.50 and the delta value
(A) of visual grading score of Formulation Example 2 was 10.50 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and ellagic acid hydrate in Formulation Example 2.
Test Example 3: Evaluation of the pigmentation improvement effect-3
The following test was performed using colored guinea pigs for evaluating the effect of improving pigmentation obtained by the combined use of AMP and tranexamic acid. 1. Preparation of a test solution
Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 3% by weight tranexamic acid (Formulation Example 3), a solution
comprising 3% by weight AMP2Na (Comparative Formulation Example 3-1), and a solution comprising 3% by weight tranexamic acid (Comparative Formulation Example 2-2) were prepared.
2. Production of an animal model with pigmentation
The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal.

Following the procedure of Test Example 1, the test was performed using the eight colored guinea pigs.

The delta value (A) of visual grading score was calculated in the same manner as in Test Example 1 above.

The obtained results are shown in Figure 3, in which the delta values (A) of visual grading scores that were obtained by subtracting the visual grading scores before the application of the test solution from the visual grading scores 14 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 3-1 and 3-2 were 1.75 and 1.25, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 3 was 4.50. The fact that the sum of the delta values (A) of visual grading scores of Comparative Formulation Examples 3-1 and 3-2 was 3.00 and the delta value (A) of visual grading scores of Formulation Example 3 was 4.50 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and
tranexamic acid in Formulation Example 3.
Test Example 4: Evaluation of the pigmentation improvement
effect-4

1. Preparation of a test solution
Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 0.3% by weight 4-n-hexylresorcinol (Formulation Example 4), a solution comprising 3% by weight AMP2Na (Comparative Formulation Example 4-1), and a solution comprising 0.3% by weight 4-n-hexylresorcinol (Comparative Formulation Example 4-2) were prepared.
2. Production of an animal model with pigmentation
The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal.

Following the procedure of Comparative Test Example 1,
the test was performed and the delta value (A) of visual grading score was calculated.

The obtained results are shown in Figure 4, in which the delta values (A) of visual grading scores that were obtained by subtracting the visual grading scores before the application of the test solution from the visual comparison grade 14 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 4-1 and 4-2 were 1.25 and 1.75, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 4 was 7.25. The fact that the sum of
the delta values (A) of visual grading scores of Comparative Formulation Examples 4-1 and 4-2 was 3.00 and the delta value (A) of visual grading score of Formulation Example 4 was 7.25 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and 4-n-hexylresorcinol in Formulation Example 4.
Test Example 5: Evaluation of the pigmentation improvement
effect-5

1. Preparation of a test solution
Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 5% by weight chamomile extract (trade name "chamomile liquid", manufactured by ICHIMARU PHARCOS CO., LTD) (Formulation Example 5), a solution comprising 3% by weight AMP2Na (Comparative Formulation Example 5-1), and a solution comprising 5% by weight chamomile extract (Comparative Formulation Example 5-2) were prepared.
2. Production of an animal model with pigmentation
The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal.

Following the procedure of Comparative Test Example 1, the test was performed and the delta value (A) of visual grading score was calculated.

The obtained results are shown in Figure 5, in which the delta values (A) of visual grading scores that were
obtained by subtracting the visual grading scores before the application of the test solution from the visual grading scores 14 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 5-1 and 5-2 were 1.13 and 0.50, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 5 was 3.00. The fact that the sum of the delta values (A) of visual grading scores of Comparative Formulation Examples 5-1 and 5-2 was 1.63 and the delta value (A) of visual grading score of Formulation Example 5 was 3.00 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and 4-n-hexylresorcinol.
Test Example 6: Evaluation of the pigmentation improvement
effect-6

1. Preparation of a test solution
Using a 20% by weight ethanol aqueous solution as a base material, a mixed solution of 3% by weight AMP2Na and 1% by weight coenzyme Q10 (Formulation Example 6), a solution comprising 3% by weight AMP2Na (Comparative Formulation Example 6-1), and a solution comprising 1% by weight coenzyme Q10 (Comparative Formulation Example 6-2) were prepared.
2. Production of an animal model with pigmentation
The hair on the back of eight colored guinea pigs was shaved, and the shaved back of each guinea pig was exposed to ultraviolet irradiation several times, thereby producing four skin pigmentation sites per animal.

Following the procedure of Comparative Test Example 1, the test was performed and the delta value (A) of visual
grading score was calculated.

The obtained results are shown in Figure 6, in which the delta values (A) of visual grading scores that were obtained by subtracting the visual comparison grade before the application of the test solution from the visual grading scores 14 days after the application. The delta values (A) of visual grading scores of Comparative Formulation Examples 6-1 and 6-2 were 1.25 and 0.63, respectively, and in contrast, the delta value (A) of visual grading score of the solution of Formulation Example 6 was 3.88. The fact that the sum of the delta values (A) of visual grading scores of Comparative Formulation Examples 6-1 and 6-2 was 1.88 and the delta value (A) of visual grading score of Formulation Example 6 was 3.88 clearly showed that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na coenzyme Q10.
Test Example 7; Evaluation of the pigmentation improvement effect-7
Using linolic acid in place of arbutin, the same test as described in Test Example 1 is performed, and the test confirms that the pigmentation improvement effect is synergistically enhanced by the combined use of AMP2Na and linolic acid in the same manner as shown in the results of Test Example 1.
INDUSTRIAL APPLICABILITY
The composition for preventing or improving skin pigmentation of the invention comprises AMP or a salt thereof as an ingredient (A) and a specific melanin formation inhibitor or ubiquinone as an ingredient (B) in combination, and therefore the actions of preventing or improving skin pigmentation of both ingredients (A) and (B) are
synergistically enhanced. Thus, since the composition for preventing or improving skin pigmentation of the invention exhibits a superior skin pigmentation prevention or improvement effect, the composition of the invention is useful as a cosmetics and externally-applied preparation for the skin (pharmaceutical composition) for the purpose of skin-lightening, skin anti-aging, reduction of skin dullness, and amelioration of melanoma.
The ingredients (A) and (B) used as an active ingredient in the composition for preventing or improving skin pigmentation of the invention are confirmed to be highly safe, and thus can be used daily as a cosmetic material. Therefore, users can prevent or improve skin pigmentation simply and easily by the daily use, as cosmetics, of the composition for preventing or improving pigmentation of the invention.

WE CLAIM
1. A composition for preventing or improving pigmentation, the composition comprising:
at least one member (A) selected from the group consisting of adenosine
5'- monophosphates and salts thereof; and
at least one member (B) selected from the group consisting of arbutins, ellagic acid, 4-
alkylresorcinols, tranexamic acid, salts thereof, chamomile extracts, and ubiquinones
wherein the composition comprises said at least one member (A) in a total proportion
of 0.05 to 10% by weight based on a total weight of the composition, and,
said at least one member (B)) in a total proportion of 0.0001 to 50% by weight based
on a total weight of the composition.
2. The composition as claimed in claim 1, as and when used as a cosmetic or pharmaceutical composition for preventing or improving pigmentation.

Documents:

2180-DELNP-2007-Abstract-(28-11-2011).pdf

2180-delnp-2007-abstract.pdf

2180-DELNP-2007-Claims-(27-04-2012).pdf

2180-DELNP-2007-Claims-(28-11-2011).pdf

2180-delnp-2007-claims.pdf

2180-DELNP-2007-Correspondence Others-(23-02-2012).pdf

2180-DELNP-2007-Correspondence Others-(27-04-2012).pdf

2180-DELNP-2007-Correspondence Others-(28-11-2011).pdf

2180-DELNP-2007-Correspondence Others-(29-06-2012).pdf

2180-delnp-2007-correspondence-others.pdf

2180-delnp-2007-description (complete).pdf

2180-DELNP-2007-Drawings-(28-11-2011).pdf

2180-delnp-2007-drawings.pdf

2180-DELNP-2007-Form-1-(28-11-2011).pdf

2180-delnp-2007-form-1.pdf

2180-DELNP-2007-Form-2-(28-11-2011).pdf

2180-delnp-2007-form-2.pdf

2180-DELNP-2007-Form-3-(27-04-2012).pdf

2180-DELNP-2007-Form-3-(28-11-2011).pdf

2180-delnp-2007-form-3.pdf

2180-delnp-2007-form-5.pdf

2180-DELNP-2007-GPA-(28-11-2011).pdf

2180-delnp-2007-pct-101.pdf

2180-delnp-2007-pct-210.pdf

2180-delnp-2007-pct-304.pdf

2180-delnp-2007-pct-308.pdf

2180-DELNP-2007-Petition-137-(28-11-2011).pdf

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Patent Number

253033

Indian Patent Application Number

2180/DELNP/2007

PG Journal Number

25/2012

Publication Date

22-Jun-2012

Grant Date

18-Jun-2012

Date of Filing

21-Mar-2007

Name of Patentee

OTSUKA PHARMACEUTICAL CO., LTD.,

Applicant Address

9, KANDATSUKASA-CHO 2-CHOME, CHIYODA-KU, TOKYO 101-8535, JAPAN

Inventors:

#	Inventor's Name	Inventor's Address
1	FUMIKI HARANO, SHIGEO SHINOHARA AND MASAHIKO TANAKA	C/O OTSUKA PHARMACEUTICAL CO. LTD., 3-31-13 SAIGAWA, OTSU-SHI, SHIGA 5200002,JAPAN

PCT International Classification Number

A61K 8/00

PCT International Application Number

PCT/JP2005/017363

PCT International Filing date

2005-09-21

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	2004-274454	2004-09-22	Japan
2	2004-376562	2004-12-27	Japan
3	2005-194428	2005-07-01	Japan