METHOD FOR SUPPRESSING THE DISCOLORATION OF AN EXTERNAL COMPOSITION CONTAINING ADENOSINE MONOPHOSPHATE AND TRANEXAMIC ACID

Description

Technical Field

[0001] The present application relates to a method for suppressing discoloration of a composition for external use comprising an adenosine monophosphate and / or a salt thereof and tranexamic acid and / or a salt thereof, and to such composition suppressed in discoloration.Background Art

[0002] 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.

[0003] 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.

[0004] Patent Document 1 discloses a composition for preventing or improving pigmentation comprising an adenosine monophosphate and tranexamic acid.

[0005] DATABASE GNPD [Online], MINTEL; 29 May 2001 (2001-05-29), anonymous: "Luminizing Night Essence Lotion", Database accession no. 10086323, discloses a cosmetic composition for external use comprising disodium adenosine triphosphate, tranexamic acid and trisodium EDTA. This lotion further comprises PEG-6 and PEG-20.

[0006] DATABASE GNPD [Online], MINTEL; 1 October 2015 (2015-10-01), anonymous: "Skin Whitening Cream", Database accession no. 3514209, relates to a cosmetic composition for external use comprising adenosine monophosphate, tranexamic acid and disodium EDTA. This cream further comprises bis-ethoxydiglycol cyclohexane 1,4-dicarboxylate.

[0007] DATABASE GNPD [Online], MINTEL; 22 March 2011 (2011-03-22), anonymous: "Whitening Enliver", Database accession no. 1535818, 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-6, PEG-20 and silica.

[0008] EP 0 685 229 A1 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.

[0009] CN 104 434 766 A describes a nursing spray containing cordyceps militaris. The nursing spray contains 22 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.Prior Art DocumentPatent Document

[0010] Patent Document 1: WO 2006 / 033343Summary of InventionTechnical Problem

[0011] 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.Solution to Problem

[0012] 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.

[0013] Thus, the present application provides the following: [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. [2] A method for producing a composition for external use, comprising mixing Ingredient (A): an adenosine monophosphate and / or a salt thereof; and Ingredient (B) : tranexamic acid and / or a salt thereof, in the presence of 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. [3] A method for suppressing discoloration of a composition for external use which comprises Ingredient (A): an adenosine monophosphate and / or a salt thereof; and Ingredient (B): tranexamic acid and / or a salt thereof, comprising using 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. Effect of The Invention

[0014] 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.Description of Embodiment

[0015] The present application relates to 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.

[0016] 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).

[0017] 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.

[0018] 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 0.001 to 10% by weight based on the total weight of the composition for external use. Preferably from 0.01% by weight to 10% by weight, more preferably from 0.1% by weight to 7% by weight, more preferably from 0.5% by weight to 5% by weight, still more preferably from 0.7% by weight to 3% by weight, and even more preferably from 1% by weight to 2% by weight are exemplified.

[0019] Further examples of the lower limit of the amount range of Ingredient (A) included in the composition for external use of the application include 0.001% by weight, 0.01% by weight, 0.1% by weight, 0.5% by weight, 0.7% by weight, and 1% by weight, and examples of the upper limit include 1% by weight, 2% by weight, 3% by weight, 5% by weight, 7% by weight, and 10% by weight, and preferred examples of the range may be shown by a combination of the lower limit and the upper limit.

[0020] 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.

[0021] 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 0.001 to 10% by weight based on the total weight of the composition for external use. Preferably from 0.01% by weight to 10% by weight, more preferably from 0.1% by weight to 7% by weight, more preferably from 0.5% by weight to 5% by weight, still more preferably from 0.7% by weight to 3% by weight, and even more preferably from 1% by weight to 2% by weight are exemplified.

[0022] Further, examples of the lower limit of the amount range of Ingredient (B) included in the composition for external use of the application include 0.001% by weight, 0.01% by weight, 0.1% by weight, 0.5% by weight, 0.7% by weight, and 1% by weight, and examples of the upper limit include 1% by weight, 2% by weight, 3% by weight, 5% by weight, 7% by weight, and 10% by weight, and preferred examples of the range may be indicated by a combination of the lower limit and the upper limit.

[0023] 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.

[0024] 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.

[0025] Preferred examples of a salt of tripolyphosphoric acid include sodium tripolyphosphate and potassium tripolyphosphate.

[0026] Preferred examples of a salt of metaphosphoric acid include sodium metaphosphate and potassium metaphosphate.

[0027] Preferred examples of a salt of etidronic acid include trisodium etidronate, tetrapotassium etidronate, and tetrasodium etidronate.

[0028] 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 0.00001 to 0.5 (more preferably 0.0001 to 0.2, still more preferably 0.0002 to 0.1) based on the sum of Ingredient (A) and Ingredient (B), that is, (Ingredient (A) + Ingredient (B)): Ingredient (C) = 1: 0.00001 to 0.5 (more preferably 1: 0.0001 to 0.2, still more preferably 1: 0.0002 to 0.1). 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 1 include 0.00001, 0.0001, 0.0002, 0.0005, 0.001, 0.01, 0.05, examples of the upper limit value include 0.05, 0.1, 0.2, 0.5, and preferred examples of the range may be indicated by a combination of the lower limit value and the upper limit value.

[0029] 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 0.0001 to 2% by weight based on the total weight of the composition for external use. Preferably 0.0002 to 1.5% by weight, more preferably 0.0005 to 1% by weight, and more preferably 0.001 to 0.5% by weight are exemplified.

[0030] 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 0.0001% by weight, 0.0002% by weight, 0.0005% by weight, 0.001% by weight, 0.01% by weight, 0.1% by weight, and 0.2% by weight, and examples of the upper limit include 0.2% by weight, 0.5% by weight, 1% by weight, and 2% by weight, and preferred examples of the range may be indicated by a combination of the lower limit and the upper limit.

[0031] 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.

[0032] 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 5.5 to 7.5. 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.

[0033] 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 0.0001 to 4 (more preferably 0.001 to 2, still more preferably 0.005 to 1) based on the Ingredient (A), that is, Ingredient (A): Ingredient (D) = 1: 0.0001 to 4 (more preferably 1: 0.001 to 2, still more preferably 1: 0.005 to 1).

[0034] 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 1 include 0.0001, 0.001, 0.01, and 0.1, examples of the upper limit include 0.1, 0.5, 1, 2, 3, and 4, and preferred examples of the range may be indicated by a combination of the lower limit and the upper limit.

[0035] 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 40 °C or higher), highly polymerized silicone (for example, those with a kinematic viscosity of 6000 mm 2< / s or more), pullulan, polyvinylpyrrolidone, an organic fine particle (for example, silica, poly(methyl methacrylate), talc, and urethane), biosaccharide gum-1 or a mixture thereof.

[0036] 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) = 1: 0.01 to 30 (more preferably 1: 0.02 to 25, still more preferably 1: 0.1 to 20) .

[0037] 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 1 include 0.01, 0.03, 0.05, 0.1, 0.5, 0.7, 1, examples of the upper limit include 1.5, 2, 3, 5, 10, 20, 25, 30, and preferred examples of the range may be indicated by a combination of the lower limit and the upper limit.

[0038] 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 0.001 to 10% by weight based on the total weight of the composition for external use. Preferably from 0.01% by weight to 10% by weight, more preferably from 0.1% by weight to 7% by weight, more preferably from 0.5% by weight to 5% by weight, and even more preferably from 0.7% by weight to 2% by weight are exemplified.

[0039] 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 0.001% by weight, 0.01% by weight, 0.1% by weight, 0.5% by weight, 0.7% by weight, and 1% by weight, and examples of the upper limit include 1% by weight, 2% by weight, 3% by weight, 5% by weight, 7% by weight, and 10% by weight, and preferred examples of the range may be indicated by a combination of the lower limit and the upper limit.

[0040] Each ingredient that may be compounded into the composition of the present application may be in the form of a hydrate.

[0041] 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.

[0042] For example, the composition for external use of the present application may optionally further comprise water, ethanol, glycerin, BG, 1,2-pentanediol, menthol, POE hydrogenated castor oil, phenoxyethanol, flavors, and a mixture thereof.

[0043] 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.

[0044] 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.Example

[0045] 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.<Test Example 1> Chelating agent for suppressing discoloration - I

[0046] The ingredients as shown in the following table were mixed and adjusted to pH 5.5 to 7.5 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 60 °C for 2 weeks.

[0047] After the storage, a visual check was conducted to evaluate discoloration as below, ⊚: Not discolored; ∘: Almost not discolored; △: Slightly discolored; X: Markedly discolored.

[0048] The results are shown in the table below. [Table 1-1]Compar ative exampl eFormul ation exampl e 1Formul ation exampl e 2Formul ation exampl e 3Formul ation exampl e 4Formul ation exampl e 5Formul ation exampl e 6WaterBalanceBalanceBalanceBalanceBalanceBalanceBalanceAdenosine monophosphate2222222Tranexamic acid22222221,2-Pentanediol1111111Sodium tripolyphosphate0.0010.0050.010.050.10.2ResultX○⊚⊚⊚⊚⊚ [Table 1-2] Formu latio n examp le 7Formu latio n examp le 8Formu latio n examp le 9Formu latio n examp le 10Formu latio n examp le 11Formu latio n examp le 12Formu latio n examp le 13*Formu latio n examp le 14*WaterBalanc eBalanc eBalanc eBalanc eBalanc eBalanc eBalanc eBalanc eAdenosine monophosphate22222222Tranexamic acid222222221,2-Pentanediol11111111Sodium metaphosphate0.010.050.10.2Etidronic acid0.06Phytic acid0.1EDTA·2Na·2H 2 O0.2EDTA·4Na·4H 2 O0.2Result⊚⊚⊚⊚⊚○○○ *Reference Examples <Test Example 2> Chelating agent for suppressing discoloration - II

[0049] The ingredients as shown in the following table were mixed and adjusted to pH 5.5 to 7.5 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 50 °C for 6 months.

[0050] After the storage, a visual check was conducted to evaluate discoloration as below, ⊚: Not discolored; ∘: Almost not discolored; △: Slightly discolored; X: Markedly discolored.

[0051] The results are shown in the table below.

[0052] "Other ingredients" in the comparative example and each of the formulation examples consists of the same ingredients: humectants (glycerin, butylene glycol, and 1,2-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". [Table 2]Comparat ive exampleFormulat ion example 15Formulat ion example 16Formulat ion example 17Formulat ion example 18*Formulat ion example 19*WaterBalanceBalanceBalanceBalanceBalanceBalanceAdenosine monophosphate111111Tranexamic acid222222Ethanol777777Other ingredientsSuitable amountSuitable amountSuitable amountSuitable amountSuitable amountSuitable amountSodium tripolyphosphate0.2Sodium metaphosphate0.2Etidronic acid0.2Phytic acid0.2EDTA·2Na·2H 2 O0.2Resultx⊚⊚⊚○○*Reference Examples <Test Example 3> pH adjuster for suppressing discoloration

[0053] 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 5.5 to 7.5), which were filled in a closed glass container and stored at 60 °C for 2 weeks.

[0054] After the storage, a visual check was conducted to evaluate discoloration as below, ⊚: Not discolored; ∘: Almost not discolored; △: Slightly discolored; X: Markedly discolored.

[0055] The results are shown in the table below. [Table 3]Formula tion example 20Formula tion example 21Formula tion example 22Formula tion example 23Comparative exampleWaterBalanceBalanceBalanceBalanceBalanceBalanceAdenosine monophosphate222222Tranexamic acid222222Phenoxyethanol0.20.20.20.20.20.2Aminohydroxymethylpr opanediol1.1Aminomethylpropanedi ol1.1Arginine1.9Triethanolamine1.6Potassium hydroxide0.6Sodium hydroxide0.3Result⊚⊚⊚○xx <Example 4> Agent for suppressing sticky feeling and not accelerating discoloration

[0056] The ingredients as shown in the following table were mixed and adjusted to pH 5.5 to 7.5 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.(Evaluation of sticky feeling)

[0057] The comparative example and each of the formulation examples (0.5 g) were applied to the faces of three panelists. The sticky feelings of the formulation examples were evaluated as below. ⊚: Suppressed compared with the comparative example; ∘: Slightly suppressed compared with the comparative example; x: Not suppressed compared with the comparative example;

[0058] The results are shown in Table 4.(Evaluation of discoloration)

[0059] The comparative example and each of the formulation examples were filled in a closed glass container and stored at 50 °C for 1 week or 40 °C for 6 months.

[0060] After the storage, a visual check was conducted to evaluate discoloration as below, ⊚: Not discolored; ○: Almost not discolored; △: Slightly discolored; X: Markedly discolored.

[0061] The results are shown in Table 4. [Table 4-1]% by weightCompa rativ e examp leFormu latio n examp le 24Formu latio n examp le 25Formu latio n examp le 26Formu latio n examp le 27Formu latio n examp le 28Formu latio n examp le 29Formu latio n examp le 30Formu latio n examp le 31WaterBalan ceBalan ceBalan ceBalan ceBalan ceBalan ceBalan ceBalan ceBalan ceAdenosine monophosphat e222211111Tranexamic acid222222222Ethanol777777777Sodium tripolyphosp hate0.20.20.20.20.20.20.20.20.2Other ingredientsSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tBis-ethoxydiglyc ol cyclohexane dicarboxylat e0.5Diethoxyethy 1 succinate1Highly polymerized polyethylene glycol2Highly polymerized dimethicone0.02Pullulan0.1Polyvinylpyr rolidone0.1Silica2poly (methyl methacrylate )2Visual check (50 °C for 1 week)⊚⊚⊚⊚⊚⊚⊚⊚⊚Visual check (40 °C for 6 months)○○○○○○○○○Sticky feelingx⊚⊚⊚⊚⊚⊚⊚⊚ [Table 4-2] % by weightFormu latio n examp le 32Formu latio n examp le 33Formu latio n examp le 34Formu latio n examp le 35Formu latio n examp le 36Formu latio n examp le 37Formu latio n examp le 38Formu latio n examp le 39Formu latio n examp le 40WaterBalan ceBalan ceBalan ceBalan ceBalan ceBalan ceBalan ceBalan ceBalan ceAdenosine monophosphate112221221Tranexamic acid222222222Ethanol777777777Sodium tripolyphospha te0.20.20.20.20.20.20.20.20.2Other ingredientsSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tSuita ble amoun tTalc2Urethane2Biosaccharide gum-10.05PEG / PPG / Polybu tylene glycol - 8 / 5 / 3 glycerin1Diglycerin3Polyglycerin1Polyoxypropyle ne diglyceryl ether1Polyoxyethylen e methyl glucoside1Polyglyceryl-10 Eicosanedioate / Tetradecanedi oate1.5Discoloration (50 °C for 1 week)⊚⊚⊚○△△△△△Discoloration (40 °C for 6 months)○○○△-----Sticky feeling⊚⊚⊚⊚⊚⊚⊚⊚⊚

[0062] Formulation examples comprising 1% by weight, 1.5% by weight or 2% by weight of bis-ethoxydiglycol cyclohexane dicarboxylate were also tested. The results were the same as the formulation example comprising 0.5% by weight of bis-ethoxydiglycol cyclohexane dicarboxylate shown in Table 4.

[0063] Formulation examples comprising 1.5% by weight or 2% by weight of diethoxyethyl succinate were also tested. The results were the same as the formulation example comprising 1% by weight of diethoxyethyl succinate shown in Table 4.

[0064] Formulation examples comprising 2.5% by weight, 3% by weight, 3.5% by weight, 4% by weight, 4.5% by weight or 5% by weight of silica were also tested. The results were the same as the formulation example comprising 2% by weight of silica shown in Table 4.

[0065] Formulation examples comprising 2.5% by weight, 3% by weight, 3.5% by weight, 4% by weight, 4.5% by weight or 5% by weight of poly(methyl methacrylate) were also tested. The results were the same as the formulation example comprising 2% by weight of poly(methyl methacrylate) shown in Table 4.

[0066] Formulation examples comprising 2.5% by weight, 3% by weight, 3.5% by weight, 4% by weight, 4.5% by weight or 5% by weight of talc were also tested. The results were the same as the formulation example comprising 2% by weight of talc shown in Table 4.

[0067] Formulation examples comprising 2.5% by weight, 3% by weight, 3.5% by weight, 4% by weight, 4.5% by weight or 5% by weight of urethane were also tested. The results were the same as the formulation example comprising 2% by weight of urethane shown in Table 4.

[0068] Formulation examples comprising 1.5% by weight, 2% by weight, 2.5% by weight or 3% by weight of PEG / PPG / Polybutylene glycol - 8 / 5 / 3 glycerin were also tested. The results were the same as the formulation example comprising 1% by weight of PEG / PPG / Polybutylene glycol - 8 / 5 / 3 glycerin shown in Table 4.

[0069] Formulation examples comprising 1.5% by weight, 2% by weight, 2.5% by weight, 3% by weight, 3.5% by weight, 4% by weight, 4.5% by weight, or 5% by weight of polyglycerin were also tested. The results were the same as the formulation example comprising 1% by weight of polyglycerin shown in Table 4.

[0070] Formulation examples comprising 1.5% by weight, 2% by weight, 2.5% by weight, 3% by weight, 3.5% by weight, 4% by weight, 4.5% by weight, or 5% by weight of polyoxypropylene diglyceryl ether were also tested. The results were the same as the formulation example comprising 1% by weight of polyoxypropylene diglyceryl ether shown in Table 4.

[0071] Formulation examples comprising 2% by weight, 2.5% by weight, 3% by weight, 3.5% by weight, 4% by weight, 4.5% by weight, or 5% by weight of Polyglyceryl-10 Eicosanedioate / Tetradecanedioate were also tested. The results were the same as the formulation example comprising 1.5% by weight of Polyglyceryl-10 Eicosanedioate / Tetradecanedioate shown in Table 4.Formulation example 41: Skin lotion<Ingredients>% by weight

[0072] Adenosine phosphate1.5Tranexamic acid1.5Glycerin8Butylene glycol4Hydroxylated lecithin0.1Hyaluronic acid0.02Polyoxyethylene polyoxypropylene decyl tetradecyl ether0.2Etidronic acid0.02AminomethylpropanediolSuitable amountPreservativeSuitable amountFlavorSuitable amountPurified waterBalance <Manufacturing method>

[0073] 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.Formulation Example 42: White-turbid skin lotion<Ingredients> % by weight

[0074] Adenosine phosphate0.5Tranexamic acid3Glycerin1Dipropylene glycol4Polyethylene glycol 200001Ethanol7Polyoxyethylene hydrogenated castor oil0.4Polyoxyethylene glyceryl isostearate0.2Pentaerythrityl tetraethylhexanoate0.2Sodium tripolyphosphate0.1AminohydroxymethylpropanediolSuitable amountPreservativeSuitable amountFlavorSuitable amountPurified waterBalance <Manufacturing method>

[0075] 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.Example 43: Beauty essence<Ingredients>% by weight

[0076] Adenosine phosphate1Tranexamic acid2Ascorbic acid glucoside2Glycerin8Sorbitol2Oligohyaluronic acid0.1Xanthan gum0.2Quince seed gum0.1Polyoxyethylene hydrogenated castor oil0.3Etidronic acid0.03AminomethylpropanolSuitable amountPreservativeSuitable amountAntioxidantSuitable amountFlavorSuitable amountPurified waterBalance <Manufacturing method>

[0077] 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.Formulation example 44: Beauty essence gel

[0078] Adenosine phosphate1Tranexamic acid1.5Carboxyvinyl polymer0.2PEG-240 / HDI copolymer bis-decyltetradeceth-20 ether1Xanthan gum0.2Polyoxyethylene polyoxypropylene decyl tetradecyl ether0.3Diethoxyethyl succinate1.5Butylene glycol5Glycerin3Sodium tripolyphosphate0.1AminohydroxymethylpropanediolSuitable amountPreservativeSuitable amountAntioxidantSuitable amountFlavorSuitable amountPurified waterBalance <Manufacturing method>

[0079] 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.Formulation example 45: Gel emulsion<Ingredients>% by weight

[0080] Adenosine Phosphate0.5Tranexamic Acid2Carboxyvinyl polymer0.2Acrylate / alkyl methacrylate copolymer0.5Glycerin6Dipropylene glycol4Cyclopentasiloxane5Dimethicone1Dimethiconol0.2Aminopropyl dimethicone0.1Liquid isoparaffin2Sodium metaphosphate0.4ArginineSuitable amountPreservativeSuitable amountAntioxidantSuitable amountFlavorSuitable amountPurified waterBalance <Manufacturing method>

[0081] 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.Formulation Example 46: Emulsion<Ingredient>% by weight

[0082] Adenosine phosphate0.5Tranexamic acid2Glycerin5Butylene glycol3Polyoxyethylene hydrogenated castor oil3Pentaerythrityl tetraethylhexanoate4Phytosteryl / behenyl / octyldodecyl lauroyl glutamate0.5Xanthan gum0.4EDTA-2Na0.3AminomethylpropanediolSuitable amountPreservativeSuitable amountAntioxidantSuitable amountFlavorSuitable amountPurified waterBalance <Manufacturing method>

[0083] 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.Example 47: Cream<Ingredients>% by weight

[0084] Adenosine phosphate1.5Tranexamic acid2Glycerin5Trehalose1Polyoxyethylene glyceryl monoisostearate2Glyceryl stearate3Sodium stearoyl glutamate0.5Triethylhexanoin8Liquid paraffin7Vaseline1Dimethicone0.5Behenyl alcohol3Stearic acid2Polyvinyl alcohol0.5Hydroxyethyl cellulose0.5Phytic acid0.4AminohydroxymethylpropanediolSuitable amountPreservativeSuitable amountAntioxidantSuitable amountFlavorSuitable amountPurified waterBalance <Manufacturing method>

[0085] 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 cream.

Claims

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.

2. The composition according to claim 1, wherein Ingredient (D) is selected from aminohydroxymethylpropanediol, aminomethylpropanol, aminomethylpropanediol, arginine, triethanolamine, and a mixture thereof.

3. The composition according to claim 1 or 2, wherein Ingredient (C) is comprised in a weight ratio of (Ingredient (A) + Ingredient (B)): Ingredient (C) = 1: 0.0001 to 0.5.

4. The composition according to any one of claims 1 to 3, which comprises Ingredient (D) and has pH of 5.5 to 7.5.

5. The composition according to any one of claims 1 to 4, wherein Ingredient (D) is comprised in a weight ratio of Ingredient (A): Ingredient (D) = 1: 0.00001 to 4.

6. The composition according to any one of claims 1 to 5, which comprises 0.01 to 10% by weight of Ingredient (A).

7. The composition according to any one of claims 1 to 6, which comprises 0.01 to 10% by weight of Ingredient (B).

8. The composition according to any one of claims 1 to 7, further comprising Ingredient (E): bis-ethoxydiglycol cyclohexane dicarboxylate, diethoxyethyl succinate, highly polymerized polyethylene glycol, highly polymerized silicone, pullulan, polyvinylpyrrolidone, an organic fine particle, biosaccharide gum-1, or a mixture thereof.

9. A method for producing a composition for external use, comprising mixing Ingredient (A): an adenosine monophosphate and / or a salt thereof; and Ingredient (B): tranexamic acid and / or a salt thereof, in the presence of 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.

10. A method for suppressing discoloration of a composition for external use which comprises Ingredient (A): an adenosine monophosphate and / or a salt thereof; and Ingredient (B): tranexamic acid and / or a salt thereof, comprising using 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.

11. The method according to claim 9, wherein Ingredient (D) is selected from aminohydroxymethylpropanediol, aminomethylpropanol, aminomethylpropanediol, arginine, triethanolamine, and a mixture thereof.

12. The method according to claim 10, wherein Ingredient (D) is selected from aminohydroxymethylpropanediol, aminomethylpropanol, aminomethylpropanediol, arginine, triethanolamine, and a mixture thereof.