Patent Description:
An adenosine phosphate is known to have a moisturizing effect and a whitening effect, and cosmetics comprising an adenosine phosphate have already been put on the market.

Tranexamic acid has an anti-plasmin effect and is blended in cosmetics as an active ingredient for improving rough skin and whitening, and such cosmetics have already been on the market.

Patent Document <NUM> discloses a composition for preventing or improving pigmentation comprising an adenosine monophosphate and tranexamic acid.

<NPL>, discloses a cosmetic composition for external use comprising disodium adenosine triphosphate, tranexamic acid and trisodium EDTA. This lotion further comprises PEG-<NUM> and PEG-<NUM>.

<NPL>, relates to a cosmetic composition for external use comprising adenosine monophosphate, tranexamic acid and disodium EDTA. This cream further comprises bis-ethoxydiglycol cyclohexane <NUM>,<NUM>-dicarboxylate.

<NPL>, exemplifies a cosmetic composition for external use comprising disodium adenosine triphosphate, tranexamic acid and trisodium EDTA, as well as sodium hexametaphosphate. This serum further comprises PEG-<NUM>, PEG-<NUM> and silica.

<CIT> describes a preparation for external application to the skin which comprises disodium adenosine triphosphate and tranexamic acid for prevention of skin roughening and skin improvement. The preparation further contains ginseng extract.

<CIT> describes a nursing spray containing cordyceps militaris. The nursing spray contains <NUM> active ingredients including aloe yeast, hydrolyzed oat protein, a cordyceps sinensis extracting solution, hydrolyzed royal jelly, a purslane extract, a persimmon leaf extract, an orange peel extract, a scutellaria baicalensis root extract, a phellinus linteus extract, a white willow bark extract, a vanilla extract, a Lengxiang rose extract, a mung bean extract, a green tea extract, an illicium verum extract, an astragalus membranaceus extract, a panax ginseng extract, a tricholoma matsutake extract, a rice bran extract, a jasmine extract, a peach kernel extract and a linalool leaf extract.

The present inventors tried to develop a composition comprising an adenosine monophosphate and tranexamic acid, and encountered the problem that the composition discolored with time (especially yellowing). An object of the present invention is to provide a method for suppressing discoloration with time in a composition comprising an adenosine monophosphate and/or a salt thereof and tranexamic acid and/or a salt thereof, and to provide a composition in which the discoloration is suppressed.

The present inventors have studied intensively to solve the above problem, and found that specific chelating agents and specific pH adjusters can respectively suppress the discoloration with time of a composition comprising an adenosine monophosphate and/or a salt thereof and tranexamic acid and/or a salt thereof, thereby reaching the present invention. In addition, there has been a problem that such compositions provide a sticky feeling due to an adenosine monophosphate and/or a salt thereof, and the present inventors have found that it is preferable to blend specific ingredient(s) (ingredients for suppressing sticky feeling) in order to suppress the sticky feeling, and further found that some specific ingredient(s) among these ingredients for suppressing sticky feeling do not deteriorate the discoloration with time.

Thus, the present application provides the following:.

The present invention provides a composition for external use, comprising an adenosine monophosphate and/or a salt thereof, and tranexamic acid and/or a salt thereof, in which the discoloration with time is suppressed.

The present application relates to a composition for external use, comprising.

The composition comprising an adenosine monophosphate and/or a salt thereof and tranexamic acid and/or a salt thereof may be inhibited from discoloration with time by compounding Ingredient (C) and/or Ingredient (D).

In the present application, a salt of adenosine monophosphate is not particularly limited as long as it can be formulated in a cosmetic, a drug or quasi-drug for external use. Examples of a salt of adenosine monophosphate include specifically alkali metal salts such as sodium salts, potassium salts; alkaline earth metal salts such as calcium salts, magnesium salts, barium salts; basic amino acid salts such as arginine, lysine; ammonium salts such as ammonium salts, tricyclohexylammonium salts; alkanolamine salts such as monoethanolamine salts, diethanolamine salts, triethanolamine salts, monoisopropanolamine salts, diisopropanolamine salts, triisopropanolamine, and a single kind of the salt of adenosine monophosphate may be used, or any combination of two or more kinds of the salt of adenosine monophosphate may be used.

The amount of Ingredient (A) included in the composition of the present application may vary depending on the use or form of the composition for external use, but may be optionally selected from a range of, for example, usually <NUM> to <NUM>% by weight based on the total weight of the composition for external use. Preferably from <NUM>% by weight to <NUM>% by weight, more preferably from <NUM>% by weight to <NUM>% by weight, more preferably from <NUM>% by weight to <NUM>% by weight, still more preferably from <NUM>% by weight to <NUM>% by weight, and even more preferably from <NUM>% by weight to <NUM>% by weight are exemplified.

Further examples of the lower limit of the amount range of Ingredient (A) included in the composition for external use of the application include <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, and <NUM>% by weight, and examples of the upper limit include <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, and <NUM>% by weight, and preferred examples of the range may be shown by a combination of the lower limit and the upper limit.

In the present application, a salt of tranexamic acid is not particularly limited as long as it can be formulated in a cosmetic, a drug or quasi-drug for external use. Examples of a salt of tranexamic acid include alkali metal salts, alkaline earth metal salts, basic amino acid salts, ammonium salts, alkanolamine salts, as mentioned above for an adenosine monophosphate, and a single kind of salt of tranexamic acid may be used, or any combination of two or more kinds of salt of tranexamic acid may be used.

The amount of Ingredient (B) included in the composition of the present application may vary depending on the use or form of the composition for external use, but may be optionally selected from, for example, a range of usually <NUM> to <NUM>% by weight based on the total weight of the composition for external use. Preferably from <NUM>% by weight to <NUM>% by weight, more preferably from <NUM>% by weight to <NUM>% by weight, more preferably from <NUM>% by weight to <NUM>% by weight, still more preferably from <NUM>% by weight to <NUM>% by weight, and even more preferably from <NUM>% by weight to <NUM>% by weight are exemplified.

Further, examples of the lower limit of the amount range of Ingredient (B) included in the composition for external use of the application include <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, and <NUM>% by weight, and examples of the upper limit include <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, and <NUM>% by weight, and preferred examples of the range may be indicated by a combination of the lower limit and the upper limit.

Examples of the chelating agent for Ingredient (C) include tripolyphosphoric acid or a salt thereof, metaphosphoric acid or a salt thereof, and etidronic acid or a salt thereof, and a single kind of the chelating agent may be used, or any combination of two or more kinds of the chelating agent may be used. In the composition of the present application, chelating agent(s) other than Ingredient (C) may be used to the extent that discoloration with time is not problematic.

Examples of a salt of tripolyphosphoric acid, a salt of metaphosphoric acid, a salt of etidronic acid include alkali metal salts, alkaline earth metal salts, basic amino acid salts, ammonium salts, alkanolamine salts, as mentioned above for an adenosine monophosphate. A single kind of the salt of these may be used, or any combination of two or more kinds of the salt of these may be used.

Preferred examples of a salt of tripolyphosphoric acid include sodium tripolyphosphate and potassium tripolyphosphate.

Preferred examples of a salt of metaphosphoric acid include sodium metaphosphate and potassium metaphosphate.

Preferred examples of a salt of etidronic acid include trisodium etidronate, tetrapotassium etidronate, and tetrasodium etidronate.

In the composition for external use of the present application, the amount of Ingredient (C) is not particularly limited as long as the discoloration with time of the composition is suppressed, but it is preferable that Ingredient (C) is comprised in a weight ratio of <NUM> to <NUM> (more preferably <NUM> to <NUM>, still more preferably <NUM> to <NUM>) based on the sum of Ingredient (A) and Ingredient (B), that is, (Ingredient (A) + Ingredient (B)): Ingredient (C) = <NUM>: <NUM> to <NUM> (more preferably <NUM>: <NUM> to <NUM>, still more preferably <NUM>: <NUM> to <NUM>). Further, examples of the lower limit value of the weight ratio range of Ingredient (C) when the total weight of Ingredient (A) and Ingredient (B) comprised in the composition for external use of the present application is <NUM> include <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, examples of the upper limit value include <NUM>, <NUM>, <NUM>, <NUM>, and preferred examples of the range may be indicated by a combination of the lower limit value and the upper limit value.

The amount of Ingredient (C) that may be comprised in the composition of the present application may be optionally selected, for example, from a range of usually <NUM> to <NUM>% by weight based on the total weight of the composition for external use. Preferably <NUM> to <NUM>% by weight, more preferably <NUM> to <NUM>% by weight, and more preferably <NUM> to <NUM>% by weight are exemplified.

Further examples of the lower limit of the amount range of Ingredient (C) that may be included in the composition for external use of the application include <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, and <NUM>% by weight, and examples of the upper limit include <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, and <NUM>% by weight, and preferred examples of the range may be indicated by a combination of the lower limit and the upper limit.

Examples of a pH adjuster which is an organic alkali compound of Ingredient (D) include aminohydroxymethylpropanediol, aminomethylpropanol, aminomethylpropanediol, arginine, and triethanolamine, and a single kind of the pH adjuster may be used, or any combination of two or more kinds of the pH adjuster may be used. Preferred examples of a pH adjuster which is an organic alkali compound include aminohydroxymethylpropanediol, aminomethylpropanediol, and arginine.

In order to suppress discoloration with time, it is preferable to use the pH adjuster of Ingredient (D) for adjusting the pH of the composition for external use of the present application. The preferred pH of the composition for external use of the present application may vary depending on the use of the composition, but may be pH <NUM> to <NUM>. In order to adjust pH of the composition for external use of the present application, a pH adjuster other than Ingredient (D) may be used to the extent that discoloration with time is not problematic.

In the composition for external use of the present application, the amount of Ingredient (D) is not particularly limited as long as the discoloration with time of the composition is suppressed, and may vary depending on the amount of Ingredient (A), the kind and amount of optional ingredient(s), and the preferable pH of the composition, but for example, Ingredient (D) may be comprised in a weight ratio of <NUM> to <NUM> (more preferably <NUM> to <NUM>, still more preferably <NUM> to <NUM>) based on the Ingredient (A), that is, Ingredient (A): Ingredient (D) = <NUM>: <NUM> to <NUM> (more preferably <NUM>: <NUM> to <NUM>, still more preferably <NUM>: <NUM> to <NUM>).

Further, examples of the lower limit of the weight ratio range of Ingredient (C) when the weight of Ingredient (A) comprised in the composition for external use of the present application is <NUM> include <NUM>, <NUM>, <NUM>, and <NUM>, examples of the upper limit include <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and <NUM>, and preferred examples of the range may be indicated by a combination of the lower limit and the upper limit.

The composition suppressed in sticky feeling and suppressed in discoloration with time can be provided by compounding Ingredient (E): bis-ethoxydiglycol cyclohexane dicarboxylate, diethoxyethyl succinate, highly polymerized polyethylene glycol (for example, those with a freezing point of <NUM> or higher), highly polymerized silicone (for example, those with a kinematic viscosity of <NUM><NUM>/s or more), pullulan, polyvinylpyrrolidone, an organic fine particle (for example, silica, poly(methyl methacrylate), talc, and urethane), biosaccharide gum-<NUM> or a mixture thereof.

In order to provide better suppression of sticky feeling in the composition for external use of the present application, it is preferable that Ingredient (A) and Ingredient (E) are comprised in a weight ratio of Ingredient (A): Ingredient (E) = <NUM>: <NUM> to <NUM> (more preferably <NUM>: <NUM> to <NUM>, still more preferably <NUM>: <NUM> to <NUM>).

Further, examples of the lower limit of the range of the weight ratio of Ingredient (E) when the weight of Ingredient (A) comprised in the composition for external use of the present application is <NUM> include <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, examples of the upper limit include <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and preferred examples of the range may be indicated by a combination of the lower limit and the upper limit.

The amount of Ingredient (E) included in the composition of the present application may vary depending on the kind of Ingredient (E) to be used and the use or form of the composition for external use, but may be optionally selected from a range of, for example, usually <NUM> to <NUM>% by weight based on the total weight of the composition for external use. Preferably from <NUM>% by weight to <NUM>% by weight, more preferably from <NUM>% by weight to <NUM>% by weight, more preferably from <NUM>% by weight to <NUM>% by weight, and even more preferably from <NUM>% by weight to <NUM>% by weight are exemplified.

Further, examples of the lower limit of the amount range of Ingredient (E) included in the composition for external use of the present application include <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, and <NUM>% by weight, and examples of the upper limit include <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, and <NUM>% by weight, and preferred examples of the range may be indicated by a combination of the lower limit and the upper limit.

Each ingredient that may be compounded into the composition of the present application may be in the form of a hydrate.

The composition for external use of the present application may be prepared in various forms by combining pharmaceutically or cosmetically acceptable base(s) or carrier(s) in addition to the above ingredients. For pharmaceutically or cosmetically acceptable base(s) and carrier(s), conventionally known one(s) can be used. The composition of the present invention may comprise, if required, a wide variety of known ingredients used for externally-applied compositions suitable for the skin or mucous membranes, such as cosmetics or externally-applied medical/quasi-medical drugs. Examples of such ingredients include surfactants, colorants (dyes and pigments), flavors, preservatives, bactericides (antibacterials), thickeners, antioxidants, sequestering agents, cooling agents, deodorizers, humectants, UV absorbers, UV dispersants, vitamins, plant extracts, skin astringents, antiinflammatory agents (antiphlogistic agents), whitening agents, cell activators, vasodilators, blood circulation accelerators, skin function accelerators.

For example, the composition for external use of the present application may optionally further comprise water, ethanol, glycerin, BG, <NUM>,<NUM>-pentanediol, menthol, POE hydrogenated castor oil, phenoxyethanol, flavors, and a mixture thereof.

The composition for external use of the present invention may be used as a composition for external use to be applied or sprayed on the skin. Specifically, the composition of the present invention may be used as an external preparation (skin preparation) for cosmetics, external medicines or external quasi-medicines.

The form of the composition for external use of the present invention is not particularly limited as long as it can be applied to the skin, and examples thereof include a paste, a mousse, a gel, a liquid, a milky liquid, a suspension liquid, a cream, an ointment, a solid, a sheet, an aerosol, a spray, and a liniment. Especially when using as a cosmetic, lotion; emulsions such as emollient emulsion, milky lotion, nourishing emulsion, and cleansing emulsion; cream such as emollient cream, massage cream, cleansing cream, and makeup cream; a lip balm.

The present invention is explained in further detail with reference to Formulation Examples and Test Examples. However, the scope of the invention is not limited to these Examples.

The ingredients as shown in the following table were mixed and adjusted to pH <NUM> to <NUM> with potassium hydroxide to provide the comparative example and each of the formulation examples, which were filled in a closed glass container and stored at <NUM> for <NUM> weeks.

After the storage, a visual check was conducted to evaluate discoloration as below,.

The results are shown in the table below.

The ingredients as shown in the following table were mixed and adjusted to pH <NUM> to <NUM> with potassium hydroxide to prepare the comparative example and each of the formulation examples, which were filled in a closed glass container and stored at <NUM> for <NUM> months.

"Other ingredients" in the comparative example and each of the formulation examples consists of the same ingredients: humectants (glycerin, butylene glycol, and <NUM>,<NUM>-pentanediol), touch improver (bis-ethoxydiglycol cyclohexane dicarboxylate), preservative (phenoxyethanol), solubilizer (POE hardened castor oil), and flavor, and the comparative example and each of the formulation examples comprised the same amount of "Other ingredients".

The ingredients as shown in the following table were mixed to provide the comparative example and each of the formulation examples (pH of these examples were <NUM> to <NUM>), which were filled in a closed glass container and stored at <NUM> for <NUM> weeks.

The ingredients as shown in the following table were mixed and adjusted to pH <NUM> to <NUM> with potassium hydroxide to prepare the comparative example and each of the formulation examples. In "Other ingredients", a preservative (phenoxyethanol), a solubilizing agent and a flavor were comprised.

The comparative example and each of the formulation examples (<NUM>) were applied to the faces of three panelists. The sticky feelings of the formulation examples were evaluated as below.

The comparative example and each of the formulation examples were filled in a closed glass container and stored at <NUM> for <NUM> week or <NUM> for <NUM> months.

Formulation examples comprising <NUM>% by weight, <NUM>% by weight or <NUM>% by weight of bis-ethoxydiglycol cyclohexane dicarboxylate were also tested. The results were the same as the formulation example comprising <NUM>% by weight of bis-ethoxydiglycol cyclohexane dicarboxylate shown in Table <NUM>.

Formulation examples comprising <NUM>% by weight or <NUM>% by weight of diethoxyethyl succinate were also tested. The results were the same as the formulation example comprising <NUM>% by weight of diethoxyethyl succinate shown in Table <NUM>.

Formulation examples comprising <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight or <NUM>% by weight of silica were also tested. The results were the same as the formulation example comprising <NUM>% by weight of silica shown in Table <NUM>.

Formulation examples comprising <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight or <NUM>% by weight of poly(methyl methacrylate) were also tested. The results were the same as the formulation example comprising <NUM>% by weight of poly(methyl methacrylate) shown in Table <NUM>.

Formulation examples comprising <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight or <NUM>% by weight of talc were also tested. The results were the same as the formulation example comprising <NUM>% by weight of talc shown in Table <NUM>.

Formulation examples comprising <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight or <NUM>% by weight of urethane were also tested. The results were the same as the formulation example comprising <NUM>% by weight of urethane shown in Table <NUM>.

Formulation examples comprising <NUM>% by weight, <NUM>% by weight, <NUM>% by weight or <NUM>% by weight of PEG/PPG/Polybutylene glycol - <NUM>/<NUM>/<NUM> glycerin were also tested. The results were the same as the formulation example comprising <NUM>% by weight of PEG/PPG/Polybutylene glycol - <NUM>/<NUM>/<NUM> glycerin shown in Table <NUM>.

Formulation examples comprising <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, or <NUM>% by weight of polyglycerin were also tested. The results were the same as the formulation example comprising <NUM>% by weight of polyglycerin shown in Table <NUM>.

Formulation examples comprising <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, or <NUM>% by weight of polyoxypropylene diglyceryl ether were also tested. The results were the same as the formulation example comprising <NUM>% by weight of polyoxypropylene diglyceryl ether shown in Table <NUM>.

Formulation examples comprising <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, <NUM>% by weight, or <NUM>% by weight of Polyglyceryl-<NUM> Eicosanedioate/Tetradecanedioate were also tested. The results were the same as the formulation example comprising <NUM>% by weight of Polyglyceryl-<NUM> Eicosanedioate/Tetradecanedioate shown in Table <NUM>.

According to a conventional method, the water-soluble ingredients were dissolved in purified water to provide a main phase. The water-insoluble ingredient mixed with the surfactants were added to the main phase to provide the skin lotion.

According to a conventional method, the water-soluble ingredients were dissolved in purified water to provide an aqueous phase. The water-insoluble ingredients were mixed with the surfactants with heating, and the resulting mixture was gradually added to the aqueous phase to provide the white-turbid lotion.

According to a conventional method, the water-soluble ingredients were dissolved in purified water to provide a main phase. The water-insoluble ingredients mixed with the surfactant were added to the main phase to provide the beauty essence.

The carbomer was dispersed in purified water, and then the other water-soluble ingredients were added thereto and dissolved by warming to provide a main phase. The water-insoluble ingredients mixed with the surfactant were added to the main phase. The resulting mixture was mixed uniformly and deaerated to provide the desired beauty essence gel.

The water-soluble polymers and other water-soluble ingredients were dissolved in purified water with warming to provide an aqueous phase. The oil phase, in which the oil-soluble ingredients were dissolved by warming, was dispersed in the aqueous phase and mixed with a disper, and emulsified. After mixing uniformly, the mixture was deaerated to provide the desired gel emulsion.

The water-soluble polymer and other water-soluble ingredients were dissolved in purified water with warming to provide an aqueous phase. The oil phase, in which the oil-soluble ingredients were dissolved by warming, was dispersed in aqueous phase and mixed with a disper, and emulsified. After mixing uniformly, the mixture was deaerated to provide the desired emulsion.

Claim 1:
A composition for external use, comprising:
Ingredient (A) : an adenosine monophosphate and/or a salt thereof; and
Ingredient (B): tranexamic acid and/or a salt thereof, and further comprising
Ingredient (C): a chelating agent which is a phosphate compound selected from tripolyphosphoric acid or a salt thereof, metaphosphoric acid or a salt thereof, etidronic acid or a salt thereof, and a mixture thereof; and/or
Ingredient (D): a pH adjuster which is an organic alkali compound.