Composition for external use containing ascorbic acid and / or its salt

Abstract

To provide an external composition superior in stability and use feeling.SOLUTION: According to the present invention, an external composition is prepared which includes (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least one selected from the group consisting of low-molecular-weight betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethylascorbic acid, and salts of 3-O-ethylascorbic acid, and (D) water, wherein the content of ethoxydiglycol is less than 30 mass%.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition for external use containing ascorbic acid and / or a salt thereof. [Background technology]

[0002] Ascorbic acid is known to have a variety of effects, such as anti-inflammatory effects, acne treatment effects, skin whitening effects, anti-aging effects, antioxidant effects, cell activation effects by promoting the synthesis of biological components such as collagen, and the suppression of cellular damage and DNA damage caused by ultraviolet rays in epidermal keratinocytes. For these reasons, it is widely used as an external skin preparation.

[0003] Ascorbic acid is easily oxidized in the presence of water, such as in an aqueous solution, and therefore it is necessary to reduce the amount of water in the formulation. However, a small amount of water is not enough to solubilize ascorbic acid.

[0004] For this reason, several methods have been investigated for stably solubilizing ascorbic acid in aqueous topical skin preparations (e.g., Patent Document 1: WO02 / 19972, Patent Document 2: WO00 / 78283, Patent Document 3: JP-A-2002-348228, Patent Document 4: JP-A-2005-225865). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] WO02 / 19972 publication [Patent Document 2] WO00 / 78283 publication [Patent Document 3] JP 2002-348228 A [Patent Document 4] JP 2005-225865 A Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention aims to provide an ascorbic acid-containing topical composition having good properties. [Means for solving the problem]

[0007] The present invention provides a composition for external use that contains ascorbic acid and / or a salt thereof, and that allows for the blending of ascorbic acid and / or a salt thereof at various concentrations.

[0008] According to the study by the present inventors, it was found that when ascorbic acid and / or a salt thereof is blended at a high concentration, some of the products do not dissolve during production, and even if they dissolve during production, they precipitate when stored at a low temperature, such as 4° C. Furthermore, it was found that in a formulation blended with ethoxydiglycol at a high concentration to improve the feeling of use, yellowing may occur after long-term storage, although there is no problem with the quality.

[0009] As a result of intensive research into solving the problem, the inventors have found that an external composition containing (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least one selected from the group consisting of low molecular weight betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and (D) water, and further containing less than 30% by mass of ethoxydiglycol, can inhibit precipitation of ascorbic acid and inhibit decomposition of ascorbic acid, and has excellent stability and transdermal absorbability (skin permeability), thereby completing the present invention.

[0010] That is, the present invention provides the topical compositions described below. Section 1. (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid (B) a diol having 3 carbon atoms, (C) at least one selected from the group consisting of low molecular weight betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid; (D)Water and the content of ethoxydiglycol (diethylene glycol monoethyl ether) is less than 30% by mass. Section 2. Item 2. The topical composition according to item 1, wherein the component (B) is 25% by mass or more of the topical composition. Section 3. Item 3. The composition for external use according to item 1 or 2, wherein the component (D) is 0.01 to 20 parts by mass per part by mass of the total content of the component (A). Section 4. Item 4. The composition for external use according to any one of items 1 to 3, wherein component (C) is at least one selected from the group consisting of trimethylglycine, carnitine, arginine, sodium citrate, sodium succinate, sodium pyrrolidone carboxylate, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid. Section 5. The composition for external use according to any one of items 1 to 4, wherein (B) is 1,3-propanediol or propylene glycol. Section 6. Item 6. The composition for external use according to any one of items 1 to 5, wherein the concentration of the ascorbic acid or a salt thereof is 3 to 40% by mass. Section 7. Item 7. The composition for external use according to any one of items 1 to 6, further comprising (E) a lower alcohol. Section 8 Item 8. The composition for external use according to any one of items 1 to 7, wherein ethoxydiglycol is contained in an amount of 10% by mass or less of the composition for external use. Section 9 Item 9. The composition for external use according to any one of items 1 to 8, which is substantially free of ethoxydiglycol. Section 10 Item 10. The composition for external use according to any one of items 1 to 9, wherein the composition for external use is a solubilized composition for external use having a transmittance at a wavelength of 700 nm of 85 to 100%. Section 11. Item 11. The composition for external use according to any one of Items 1 to 10, which is for promoting transdermal absorption of ascorbic acid. Section 12. A method for imparting stability to a topical composition containing (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, by combining (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) a diol having three carbon atoms, (C) at least one selected from the group consisting of low molecular weight betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and (D) water, and reducing ethoxydiglycol to less than 30 mass%. Effect of the Invention

[0011] According to the present invention, a composition for external use having excellent stability can be provided. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] In this specification, the unit of content "mass%" is synonymous with "g / 100 g".

[0013] The topical composition of the present invention comprises: The composition for external use contains (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) a diol having three carbon atoms, (C) at least one selected from the group consisting of low molecular weight betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and (D) water, and has an ethoxydiglycol content of less than 30% by mass.

[0014] The topical composition of the present invention contains (A) at least one component selected from the group consisting of ascorbic acid and salts of ascorbic acid, which is stable over a wide concentration range and is highly safe.

[0015] [(A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid] The ascorbic acid used in the present invention may be any ascorbic acid commercially available as a component of pharmaceuticals, quasi-drugs, or skin care products in the field of cosmetics, and these generally refer to the L-isomer.

[0016] Salts of ascorbic acid can also be used. Here, the salts of ascorbic acid are pharma- ceutically acceptable salts. Examples of the salts include, but are not limited to, salts with organic bases (e.g., salts with tertiary amines such as trimethylamine salts, triethylamine salts, monoethanolamine salts, triethanolamine salts, and pyridine salts, and basic ammonium salts such as arginine), salts with inorganic bases (e.g., alkali metal salts such as ammonium salts, sodium salts, and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, and aluminum salts). Particularly preferred salts of ascorbic acid are sodium salts and potassium salts. Specific examples include sodium ascorbate, sodium ascorbic acid monophosphate, sodium ascorbic acid diphosphate, sodium ascorbic acid triphosphate, and sodium ascorbic acid-2-sulfate.

[0017] In the present invention, ascorbic acid or a salt thereof can be used alone or in combination of two or more kinds.

[0018] In the topical composition of the present invention, the total content of the (A) component relative to the total amount of the topical composition is appropriately set depending on the balance with other components. The total content of the (A) component relative to the total amount of the topical composition is not particularly limited, but is preferably 0.1% by mass or more, more preferably 1% by mass or more, even more preferably 2% by mass or more, even more preferably 3% by mass or more, and most preferably 10% by mass or more. The total content of the (A) component relative to the total amount of the topical composition is preferably 50% by mass or less, more preferably 40% by mass or less, even more preferably 35% by mass or less, and even more preferably 30% by mass or less. The total content of the (A) component relative to the total amount of the topical composition is preferably 0.1% by mass to 50% by mass, more preferably 1% by mass to 40% by mass, even more preferably 3% by mass to 40% by mass, even more preferably 3% by mass to 30% by mass, and most preferably 10% by mass to 30% by mass.

[0019] [(B) Diol containing 3 carbon atoms] The diol having 3 carbon atoms used in the present invention is not particularly limited as long as it is used as a component of a skin external preparation in the fields of medicines, quasi-drugs, or cosmetics. The diol having 3 carbon atoms is not limited, but is preferably 1,3-propanediol (CAS number: 504-63-2, English name: 1,3-Dihydroxypropane or Trimethylene Glycol) or propylene glycol (CAS number: 57-55-6, English name: 1,2-Dihydroxypropane, Japanese name: 1,2-propanediol), and more preferably 1,3-propanediol. For example, either 1,3-propanediol or propylene glycol can be used as component (B). Such a diol having 3 carbon atoms can be used as a commercially available product as it is. In addition, from the viewpoint of mitigating irritation to the skin, improving the feeling of use, and suppressing coloring, a combination of 1,3-propanediol and propylene glycol is one of the preferred embodiments, and it is more preferable to include at least 1,3-propanediol as component (B).

[0020] In the topical composition of the present invention, the total content of component (B) relative to the total amount of the topical composition is not particularly limited, but is preferably 20% by mass or more, more preferably 25% by mass or more, and even more preferably 30% by mass or more. The total content of the component (B) relative to the total amount of the topical composition is preferably 90% by mass or less, more preferably 85% by mass or less, and even more preferably 80% by mass or less.

[0021] The total content of the component (B) relative to the total amount of the topical composition is preferably 20 to 90 mass %, more preferably 25 to 85 mass %, and even more preferably 30 to 80 mass %.

[0022] In the topical composition of the present invention, the ratio of the amount of component (B) to the amount of component (A) is not particularly limited, but is preferably 0.1 to 100 parts by mass, and more preferably 0.5 to 25 parts by mass, per 1 part by mass of the total content of component (A).

[0023] [(C) component] (Low molecular weight betaine) The low molecular weight betaine used in the present invention may be a compound that is commonly used as a component of skin care products in the fields of medicines, quasi-drugs, or cosmetics. In the present invention, the low molecular weight betaine refers to a compound that forms an amphoteric ion in a molecule with a molecular weight of 500 or less, and specific examples include quaternary ammonium bases, quaternary phosphonium bases, and tertiary sulfonium bases, which hardly exhibit surfactant properties. Among these, the following chemical formula is preferable:

[0024] [ka] (wherein R1, R2 and R3 each independently represent an alkyl group having 1 to 6 carbon atoms, and n represents 1 to 6).

[0025] As R1 to R3, a wide variety of straight or branched alkyl groups having 1 to 6 carbon atoms can be used. That is, examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a neopentyl group, a tert-pentyl group, a hexyl group, an isohexyl group, a 3-methylpentyl group, a 2,2-dimethylbutyl group, or a 2,3-dimethylbutyl group. R1 to R3 may be the same or different.

[0026] Specific examples include trimethylglycine, triethylglycine, tripropylglycine, and triisopropylglycine where n=1, trimethyl-β-alanine where n=2, and trimethyl-γ-aminobutyric acid where n=3, with trimethylglycine being preferred.

[0027] In addition, these low molecular weight betaines may be substituted, and specific examples thereof include N,N,N-trimethylalanine, N,N,N-triethylalanine, N,N,N-triisopropylalanine, N,N,N-trimethylmethylalanine, carnitine, acetylcarnitine, and the like, with carnitine being preferred.

[0028] These can also be synthesized, or commercially available products can be used as they are.

[0029] These low molecular weight betaines can be used alone or in combination of two or more.

[0030] In the topical composition of the present invention, the total content of the low molecular weight betaine relative to the total amount of the topical composition is appropriately set depending on the balance with other components. It is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, even more preferably 0.001% by mass or more, more preferably 0.01% by mass or more, and most preferably 0.05% by mass or more, relative to the total amount of the topical composition. The total content of the low molecular weight betaine relative to the total amount of the topical composition is preferably 30% by mass or less, more preferably 25% by mass or less, even more preferably 20% by mass or less, more preferably 15% by mass or less, and most preferably 10% by mass or less. The total content of the low molecular weight betaine relative to the total amount of the topical composition is preferably 0.00001% by mass to 30% by mass, more preferably 0.0001% by mass to 25% by mass, even more preferably 0.001% by mass to 20% by mass, and most preferably 0.01% by mass to 10% by mass.

[0031] In the topical composition of the present invention, the ratio of the amount of low molecular weight betaine to component (A) is preferably 0.00005 to 1.0 part by mass, more preferably 0.0001 to 0.8 parts by mass, even more preferably 0.0005 to 0.5 parts by mass, and most preferably 0.001 to 0.4 parts by mass, per 1 part by mass of the total content of component (A).

[0032] (organic acid salt) As the organic acid salt used in the present invention, compounds that are commonly used as ingredients of external preparations for skin in the fields of medicines, quasi-drugs, and cosmetics can be used.

[0033] The organic acid salt contributes to the stability of the topical composition of the present invention.

[0034] Here, in the present invention, an organic acid that forms an organic acid salt is an acid of an organic compound having an organic group and a molecular weight of 1000 or less, preferably 700 or less, more preferably 500 or less, and particularly preferably 300 or less. Most of the organic acids are carboxylic acids having a carboxyl group or sulfonic acids having a sulfo group. More specific examples include, but are not limited to, lactic acid, acetic acid, citric acid, tartaric acid, malic acid, succinic acid, oxalic acid, gluconic acid, fumaric acid, propionic acid, aspartic acid, pyrrolidone carboxylic acid, ε-aminocaproic acid, glutamic acid, and aminoethylsulfonic acid.

[0035] Here, the salt that forms the organic acid salt is a pharma- ceutical acceptable salt.Not limited, for example, the salt with organic base (e.g., salt with tertiary amine such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, pyridine salt, etc., basic ammonium salt such as arginine, etc.), salt with inorganic base (e.g., alkali metal salt such as ammonium salt, sodium salt, potassium salt, etc., alkaline earth metal salt such as calcium salt, magnesium salt, aluminum salt, etc.), etc. are included.Particularly preferred organic acid salt is sodium salt, calcium salt.

[0036] In the present invention, preferred organic acid salts include sodium lactate, sodium acetate, sodium citrate, sodium succinate, sodium oxalate, calcium gluconate, and sodium pyrrolidone carboxylate.

[0037] These can be synthesized, or commercially available products can be used as they are.

[0038] These organic acid salts can be used alone or in combination of two or more kinds.

[0039] In the topical composition of the present invention, the total content of the organic acid salt relative to the total amount of the topical composition is appropriately set depending on the balance with other components. The total content of the organic acid salt relative to the total amount of the topical composition is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, even more preferably 0.005% by mass or more, more preferably 0.01% by mass or more, and most preferably 0.05% by mass or more. The total content of the organic acid salt relative to the total amount of the topical composition is preferably 10% by mass or less, more preferably 9% by mass or less, even more preferably 8% by mass or less, more preferably 7% by mass or less, and most preferably 6% by mass or less. The total content of the organic acid salt relative to the total amount of the topical composition is preferably 0.0001% by mass to 10% by mass, more preferably 0.001% by mass to 9% by mass, even more preferably 0.005% by mass to 8% by mass, and most preferably 0.05% by mass to 6% by mass.

[0040] In the topical composition of the present invention, the ratio of the amount of organic acid salt to component (A) is preferably 0.00003 to 0.8 parts by mass, more preferably 0.00005 to 0.7 parts by mass, even more preferably 0.00008 to 0.6 parts by mass, and most preferably 0.0001 to 0.5 parts by mass, per 1 part by mass of the total content of component (A).

[0041] (Inorganic acid salts) As the inorganic acid salt used in the present invention, compounds that are usually used as ingredients of external preparations for skin in the fields of medicines, quasi-drugs, and cosmetics can be used.

[0042] The inorganic acid salt contributes to the stability of the topical composition of the present invention.

[0043] Here, in the present invention, more specific examples of inorganic acids include, but are not limited to, nitric acid, phosphoric acid, sulfuric acid, sulfurous acid, boric acid, and hydrofluoric acid.

[0044] Here, the salt that forms an inorganic acid salt is a pharma- ceutically acceptable salt.It is not limited to, but includes, for example, salts with inorganic bases (e.g., alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, aluminum salt, etc.).Particularly preferred inorganic acid salts are sodium salt and potassium salt.

[0045] In the present invention, preferred inorganic acid salts include sodium pyrosulfite, potassium pyrosulfite, sodium phosphate, potassium nitrate, and sodium borate, and among these, sodium pyrosulfite is preferred.

[0046] These can be synthesized, or commercially available products can be used as they are. These inorganic acid salts may be used alone or in combination of two or more kinds.

[0047] In the present invention, the total content of pyrosulfite relative to the total amount of the composition for external use is appropriately set according to the balance with other components.The total content of pyrosulfite relative to the total amount of the composition for external use is preferably 0.00001% by mass or more, more preferably 0.0001% by mass or more, even more preferably 0.0005% by mass or more, more preferably 0.001% by mass or more, and most preferably 0.005% by mass or more.The total content of pyrosulfite relative to the total amount of the composition for external use is preferably 1% by mass or less, more preferably 0.8% by mass or less, even more preferably 0.5% by mass or less, more preferably 0.4% by mass or less, and most preferably 0.3% by mass or less. The total content of pyrosulfite relative to the total amount of the topical composition is preferably 0.00001% by mass to 1% by mass, more preferably 0.0001% by mass to 0.8% by mass, even more preferably 0.0005% by mass to 0.5% by mass, and most preferably 0.005% by mass to 0.3% by mass.

[0048] In the topical composition of the present invention, the ratio of the amount of pyrosulfite to component (A) is preferably ~ parts by mass, more preferably ~ parts by mass, even more preferably ~ parts by mass, and most preferably ~ parts by mass, per 1 part by mass of the total content of component (A).

[0049] (Basic amino acid or its salt) As the basic amino acid or a salt thereof used in the present invention, compounds that are commonly used as ingredients of external skin preparations in the fields of pharmaceuticals, quasi-drugs, and cosmetics can be used.

[0050] The basic amino acid or its salt contributes to the stability of the topical composition of the present invention.

[0051] In the present invention, the basic amino acid refers to arginine, lysine, or histidine.

[0052] Here, the salt of basic amino acid is a pharmaceutically acceptable salt.Not limited to, for example, salt with organic base (e.g., salt with tertiary amine such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, pyridine salt, etc., basic ammonium salt such as arginine, etc.), salt with inorganic base (e.g., alkali metal salt such as ammonium salt, sodium salt, potassium salt, etc., alkaline earth metal salt such as calcium salt, magnesium salt, aluminum salt, etc.), etc. are included.Particularly preferred salt is sodium salt, calcium salt.

[0053] In the present invention, a preferable basic amino acid or a salt thereof is arginine.

[0054] These can be synthesized, or commercially available products can be used as they are.

[0055] These basic amino acids or salts thereof can be used alone or in combination of two or more kinds.

[0056] In the composition for external use of the present invention, the total content of the basic amino acid or its salt relative to the total amount of the composition for external use is appropriately set depending on the balance with other components. The total content of the basic amino acid or its salt relative to the total amount of the composition for external use is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, even more preferably 0.005% by mass or more, more preferably 0.01% by mass or more, and most preferably 0.05% by mass or more. The total content of the basic amino acid or its salt relative to the total amount of the composition for external use is preferably 10% by mass or less, more preferably 9% by mass or less, even more preferably 8% by mass or less, more preferably 7% by mass or less, and most preferably 6% by mass or less. The total content of the basic amino acid or its salt relative to the total amount of the composition for external use is preferably 0.0001% by mass to 10% by mass, more preferably 0.001% by mass to 9% by mass, even more preferably 0.005% by mass to 8% by mass, and most preferably 0.05% by mass to 6% by mass.

[0057] In the topical composition of the present invention, the ratio of the amount of basic amino acid or a salt thereof to component (A) is preferably 0.00003 to 0.8 parts by mass, more preferably 0.00005 to 0.7 parts by mass, even more preferably 0.00008 to 0.6 parts by mass, and most preferably 0.0001 to 0.5 parts by mass, per 1 part by mass of the total content of component (A).

[0058] (3-O-ethyl ascorbic acid or its salts) As the 3-O-ethyl ascorbic acid or a salt thereof used in the present invention, compounds that are commonly used as ingredients of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used.

[0059] 3-O-ethylascorbic acid can be synthesized by ethoxylating the hydroxyl group at the 3-position of ascorbic acid (for example, by a known method described in JP-A-8-134055). Commercially available 3-O-ethylascorbic acid can also be used as is. Examples of commercially available products include, but are not limited to, "VC Ethyl" manufactured by Nippon Fine Chemicals Co., Ltd. and products manufactured by Junsei Chemical Co., Ltd.

[0060] 3-O-ethyl ascorbic acid contributes to the stability of the topical composition of the present invention.

[0061] These can also be synthesized, or commercially available products can be used as they are.

[0062] These 3-O-ethyl ascorbic acids or salts thereof can be used alone or in combination of two or more kinds.

[0063] 3-O-ethylascorbic acid can also be used as a salt. Here, the salt of 3-O-ethylascorbic acid is a pharma- ceutically acceptable salt. It is not limited to, but includes, for example, salts with organic bases (e.g., salts with tertiary amines such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, pyridine salt, etc., basic ammonium salts such as arginine, etc.), salts with inorganic bases (e.g., alkali metal salts such as ammonium salt, sodium salt, potassium salt, etc., alkaline earth metal salts such as calcium salt, magnesium salt, etc., aluminum salt, etc.). Particularly preferred salts of 3-O-ethylascorbic acid are sodium salt and potassium salt.

[0064] In the present invention, the total content of 3-O-ethyl ascorbic acid or its salts relative to the total amount of the composition for external use is appropriately set according to the balance with other components.The total content of 3-O-ethyl ascorbic acid or its salts relative to the total amount of the composition for external use is preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, even more preferably 0.005% by mass or more, more preferably 0.01% by mass or more, and most preferably 0.02% by mass or more.The total content of 3-O-ethyl ascorbic acid or its salts relative to the total amount of the composition for external use is preferably 10% by mass or less, more preferably 8% by mass or less, even more preferably 6% by mass or less, more preferably 5% by mass or less, and most preferably 3% by mass or less. The total content of 3-O-ethyl ascorbic acid or a salt thereof relative to the total amount of the composition for external use is preferably 0.0001% by mass to 10% by mass, more preferably 0.001% by mass to 5% by mass, even more preferably 0.005% by mass to 3% by mass, and most preferably 0.01% by mass to 3% by mass.

[0065] In the topical composition of the present invention, the ratio of the amount of 3-O-ethylascorbic acid or a salt thereof to component (A) is preferably 0.00001 to 1 part by mass, more preferably 0.00005 to 0.8 parts by mass, even more preferably 0.0001 to 0.6 parts by mass, and most preferably 0.0002 to 0.5 parts by mass, per 1 part by mass of the total content of component (A).

[0066] Component (C) can contribute to greater stability and transdermal absorbability of the topical composition of the present invention.

[0067] At least one selected from the group consisting of (C) low molecular weight betaines, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid can also be used alone or in any combination of two or more thereof.

[0068] Such combinations include, but are not limited to, trimethylglycine and citrate, trimethylglycine and succinate, trimethylglycine and pyrosulfite or a salt thereof, 3-O-ethylascorbic acid or a salt thereof and citrate, 3-O-ethylascorbic acid or a salt thereof and succinate, 3-O-ethylascorbic acid or a salt thereof and trimethylglycine, 3-O-ethylascorbic acid or a salt thereof and carnitine, 3-O-ethylascorbic acid or a salt thereof and sodium pyrrolidone carboxylate, 3-O-ethylascorbic acid or a salt thereof and pyrosulfite or a salt thereof, and the like.

[0069] In the topical composition of the present invention, the total content of the (C) component relative to the total amount of the topical composition is not particularly limited, but is preferably 0.005% by mass or more, more preferably 0.01% by mass or more. The total content of the (C) component relative to the total amount of the topical composition is preferably 25% by mass or less, more preferably 15% by mass or less. The content of the (C) component relative to the total amount of the topical composition is preferably 0.005% by mass to 25% by mass, more preferably 0.01% by mass to 15% by mass.

[0070] In the topical composition of the present invention, the ratio of the amount of component (C) to component (A) is not particularly limited, but is preferably 0.00001 to 3 parts by mass, more preferably 0.0005 to 2 parts by mass, even more preferably 0.0001 to 1 part by mass, still more preferably 0.005 to 0.9 parts by mass, and most preferably 0.008 to 0.8 parts by mass, per part by mass of the total content of component (A).

[0071] [(D)Water] The composition for external use of the present invention is a liquid composition containing water. The proportion of water is not limited, but is preferably 0.01% by mass to 60% by mass, more preferably 0.01% by mass to 50% by mass, and particularly preferably 0.1% by mass to 40% by mass, based on the composition for external use.

[0072] In the topical composition of the present invention, the ratio of the amount of component (D) to component (A) is not particularly limited, but is preferably 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, and most preferably 0.2 to 3 parts by mass, per part by mass of the total content of component (A).

[0073] In one embodiment of the present invention, it is possible to suppress the precipitation of ascorbic acid or a salt thereof even in a composition containing a small amount of water, and further to suppress the decomposition of ascorbic acid.

[0074] [Ethoxydiglycol (diethylene glycol monoethyl ether)] In the present invention, mainly from the viewpoint of improving stability, ethoxydiglycol is not contained or is contained in an amount of less than 30% by mass. The ethoxydiglycol contained in the topical composition at less than 30% by mass is not particularly limited as long as it is used as a component of topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics.

[0075] In the topical composition of the present invention, the content of ethoxydiglycol relative to the total amount of the topical composition is less than 30% by mass, preferably the content of ethoxydiglycol is 10% by mass or less, more preferably the content of ethoxydiglycol is 5% by mass or less, and ethoxydiglycol may not be included in the topical composition.

[0076] The total content of ethoxydiglycol is equal to or more than 0 and less than 30% by mass, more preferably 0 to 10% by mass, and further preferably about 0 to 5% by mass.

[0077] In the topical composition of the present invention, the ratio of the amount of the ethoxydiglycol component to the amount of the component (A) is preferably 0 to 10 parts by mass, more preferably 0 to 5 parts by mass, per 1 part by mass of the total amount of the component (A).In some cases, the ratio can be 0.001 to 10 parts by mass, or 0.01 to 5 parts by mass.

[0078] The topical composition of the present invention contains (A), (B), (C), and (D), and by specifying the content of ethoxydiglycol, it becomes a stable topical composition.

[0079] [Glycol Ether] In the present invention, mainly from the viewpoint of improving stability, it is preferable that the glycol ether other than ethoxydiglycol is not contained, or even if it is contained, the total amount of glycol ethers including ethoxydiglycol is less than 40% by mass. Here, the glycol ether other than ethoxydiglycol is not particularly limited as long as it is used as a component of skin external preparations in the fields of medicines, quasi-drugs, or cosmetics. It is sufficient that it dissolves in 10 g or more in 100 g of water. Examples of the glycol ether include those with a degree of polymerization of 2 or less. Specifically, diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, diethylene glycol monoisobutyl ether, diethylene glycol dimethyl ether, ethylene glycol monobutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, triethylene glycol monobutyl ether, tetraethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether, etc. can be exemplified. Further typical examples include diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, diethylene glycol monoisobutyl ether, diethylene glycol dimethyl ether, ethylene glycol monobutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, triethylene glycol monobutyl ether, tetraethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether.Particularly typical examples are diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, ethylene glycol monobutyl ether, triethylene glycol monobutyl ether, tetraethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether.

[0080] These glycol ethers may be used alone or in combination of two or more.

[0081] In the topical composition of the present invention, the total content of glycol ethers, including ethoxydiglycol, relative to the total amount of the topical composition is preferably less than 40% by mass, more preferably less than 30% by mass, and even more preferably 10% by mass or less. Glycol ethers may not be included in the topical composition. The total content of glycol ethers including ethoxydiglycol is preferably 0 to less than 40% by mass, more preferably 0 to less than 30% by mass, even more preferably about 0 to 10% by mass, and most preferably about 0 to 5% by mass.

[0082] In the topical composition of the present invention, the ratio of the amount of the glycol ether component to the amount of the component (A) is preferably 0 to 20 parts by mass, more preferably 0 to 10 parts by mass, per part by mass of the total amount of the component (A). In some cases, the ratio can be 0.001 to 20 parts by mass, or 0.01 to 10 parts by mass.

[0083] The topical composition of the present invention contains (A), (B), (C), and (D), and by specifying the total glycol ether content, it is possible to make the topical composition stable.

[0084] [(E) Lower alcohol] From the viewpoints of improving the sensation of use, promoting stability, and promoting percutaneous absorption, the topical composition of the present invention may contain, in addition to the above-mentioned components (A), (B), (C), and (D), and, if contained, a glycol ether such as ethoxydiglycol, a lower alcohol (E), as long as the effects of the present invention are not impaired. The lower alcohol used in the present invention is not particularly limited as long as it is used as a component of a skin external preparation in the fields of medicines, quasi-drugs, or cosmetics. In this specification, the term "lower alcohol" refers to C1-C6 alcohol. Among them, C1-C3 alcohol is particularly preferably used. Examples of such alcohols include methanol, ethanol, n-propanol, isopropanol, etc.

[0085] In the topical composition of the present invention, when the component (E) is contained, the total content of the component (E) relative to the total amount of the topical composition is preferably 0.1 mass % or more, and more preferably 0.5 mass % or more. The total content of the component (E) is preferably no greater than 25% by mass, and more preferably no greater than 20% by mass.

[0086] The total content of the component (E) is preferably from 0.001 to 25 mass %, more preferably from 0.1 to 25 mass %, and even more preferably from 0.5 to 20 mass %.

[0087] In the topical composition of the present invention, the ratio of the blending amount of component (E) to component (A) is preferably 0.001 to 8 parts by mass, and more preferably 0.005 to 5 parts by mass, per part by mass of the total content of component (A).

[0088] [Polyhydric alcohol] The topical composition of the present invention may contain a polyhydric alcohol in addition to the above-mentioned components (A), (B), (C), and (D), and, if contained, less than a certain amount of ethoxydiglycol, so long as the effect of the present invention is not impaired.

[0089] The polyhydric alcohol used in the present invention is not particularly limited as long as it is used as a component of a skin external preparation in the fields of medicines, quasi-drugs, or cosmetics. The polyhydric alcohol may be added for moisturizing or as a solubilizing agent, but is not limited thereto. Specific examples include glycerin, diglycerin, dipropylene glycol, 1,3-butylene glycol, and 3-methyl-1,3-butanediol. Preferred are 1,3-butylene glycol and dipropylene glycol.

[0090] When included, the total content of polyhydric alcohol including component (B) is preferably about 10 to 90 mass%, more preferably about 20 to 80 mass%, even more preferably about 25 to 85 mass%, and particularly preferably about 30 to 70 mass%.

[0091] [Other ingredients] In addition to the above (A), (B), (C), and (D), and, if present, less than a certain amount of ethoxydiglycol, the composition for external use of the present invention may further contain one or more of various components such as whitening components, anti-inflammatory components, antibacterial components, cell activating components, astringent components, antioxidant components, acne-reducing components, anti-aging components, components promoting biocomponent synthesis such as collagen, components promoting blood circulation, moisturizing components, and anti-aging components in combination in order to enhance or supplement the various effects of ascorbic acid or to add other useful effects. Preferred are one or more of whitening components, anti-inflammatory components, antibacterial components, cell activating components, astringent components, antioxidant components, anti-aging components, and moisturizing components. Particularly preferred combinations of these components include combinations with whitening components, combinations of whitening components and antioxidant components, combinations with antioxidant components, combinations with anti-aging components, and combinations of whitening components and anti-aging components. These components are not particularly limited as long as they have been used in the past as components of topical skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics, or will be used in the future, and any components can be appropriately selected and used.

[0092] In addition to the above-mentioned components, the topical composition of the present invention may further contain a surfactant, a solubilizing component, oils and fats, sugars, or a transdermal absorption-promoting component. In particular, by adding a surfactant, a solubilizing component, or oils and fats, the stability, efficacy, and usability of ascorbic acid in an aqueous solvent can be further improved.

[0093] The topical composition of the present invention may contain various components that are generally used as components of topical preparations in the fields of medicines, quasi-drugs, or cosmetics, such as amino acids, irritation reducing agents, thickeners, preservatives, UV protection agents, colorants, dispersants, additional pH adjusters, fragrances, etc., as necessary, within quantitative and qualitative ranges that do not impair the qualities such as appearance stability and viscosity, and do not impair the effects of the present invention. These components may be used alone or in any combination of two or more.

[0094] The topical composition of the present invention contains (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least one selected from the group consisting of low molecular weight betaine, organic acid salts, inorganic acid salts, basic amino acids, salts of basic amino acids, 3-O-ethyl ascorbic acid, and salts of 3-O-ethyl ascorbic acid, and (D) water, and the content of ethoxydiglycol is less than 30% by mass. By mixing and blending the above-mentioned optional components as necessary, and further mixing other solvents and bases of topical agents that are commonly used as necessary, the composition can be prepared into various desired forms such as paste, mousse, gel, liquid, milky lotion, cream, sheet (supported by substrate), aerosol, spray, etc. These can be produced by the usual methods in the industry.

[0095] The composition for external use of the present invention is particularly preferably a transparent or translucent composition in which ascorbic acid and / or a salt thereof is solubilized. Here, "solubilized" is defined as follows. That is, for example, it refers to a composition in which the transmittance is in the range of 80 to 100%, preferably 85 to 100%, more preferably 90 to 100%, as measured at a wavelength of 700 nm using a spectrophotometer or a photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation) by ultraviolet-visible absorbance measurement. Here, the transmittance of water is taken as 100%. The solubilized composition of the present invention has a transparent or translucent appearance. The transmittance measurement method is more specifically in accordance with the method described in the 16th revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Spectroscopic Measurement Methods 2.24 Ultraviolet-Visible Absorbance Measurement Method.

[0096] [viscosity] The topical composition of the present invention can be prepared as a composition having a suitable viscosity, which is particularly desirable when the topical composition is applied to the skin. The viscosity of the topical composition of the present invention is not particularly limited, but for example, when measured at 25°C using an E-type viscometer, the viscosity is usually about 300 mPa·s or less, preferably about 200 mPa·s or less, more preferably about 100 mPa·s or less, and most preferably about 50 mPa·s or less. The viscosity measurement method is more specifically in accordance with the method described in the 16th revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Other Physical Test Methods 2.53 Viscosity Measurement Method 2. Method 2 Rotational Viscometer Method 2.1.3 Cone-Plate Type Rotational Viscometer (Cone-Plate Type Viscometer).

[0097] [pH] The topical composition of the present invention may generally have a liquid pH of 1 to 8, but from the viewpoints of the stability of ascorbic acid, low irritation to the skin and mucous membranes, and pleasant feel on the skin, it is desirable that the composition have an acidic pH of preferably 2 to 7, more preferably 2 to 6, and even more preferably 2 to 4.5.

[0098] [Application] The composition for external use of the present invention is particularly effective as a whitening agent, anti-inflammatory agent, and anti-aging agent, and has, for example, acne prevention and treatment, and antioxidant effects. Furthermore, by applying it to the skin, it may have the effect of increasing the transparency of the skin, maintaining moisture, improving the skin texture, and suppressing roughness. Furthermore, it may have the effect of making pores less noticeable, conditioning and moisturizing the skin, and can also be used to prevent and treat blemishes.

[0099] The topical composition of the present invention may be, for example, a basic cosmetic product such as a beauty essence, a skin lotion, a sunscreen cream, a milky lotion, a cream, a lotion, an oil, or a pack; a makeup cosmetic product such as a foundation, a lipstick, a lip cream, a mascara, an eyeshadow, an eyeliner, an eyebrow pencil, or a nail polish; a cleanser such as a face wash, a cleanser, or a body wash; an anti-arm odor agent, athlete's foot treatment agent, an antipruritic agent, a wound healing agent, a cleaning agent, a cleaning agent, an anti-inflammatory analgesic agent, an acne treatment agent, an agent for hemorrhoids, a germicide, a disinfectant, a skin whitening agent, an ultraviolet protection agent, or any other composition belonging to the field of cosmetics, topical medicine, or topical quasi-drug. In view of the effect on the skin, the present invention is preferably used in a product applied to the skin, such as a skin topical agent (a preparation for the skin).

[0100] [Stabilization method] The present invention also includes a method for stabilizing at least one selected from the group consisting of (A) ascorbic acid and salts of ascorbic acid. In the present invention, according to the method for stabilizing ascorbic acid, (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least one selected from the group consisting of low molecular weight betaine, organic acid salt, inorganic acid salt, basic amino acid, salt of basic amino acid, 3-O-ethyl ascorbic acid, and salt of 3-O-ethyl ascorbic acid, and (D) water are used in combination, and the content of ethoxydiglycol is less than 30% by mass, thereby making it possible to prepare a stable formulation while containing ascorbic acid or a salt thereof. In particular, it is possible to prepare a stable formulation while containing ascorbic acid or a salt thereof at a high concentration (for example, 15% by mass or more, or 20% by mass or more). That is, the present invention relates to a method for imparting stability to a topical composition containing at least one selected from the group consisting of (A) ascorbic acid and salts of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least one selected from the group consisting of low molecular weight betaine, organic acid salt, inorganic acid salt, basic amino acid, salt of basic amino acid, 3-O-ethyl ascorbic acid, and salt of 3-O-ethyl ascorbic acid, and (D) water, by using the ethoxydiglycol content less than 30% by mass. Here, the term "stabilization" refers to, but is not limited to, that stability is guaranteed even at high or low temperatures. Specifically, it refers to the suppression of precipitation of ascorbic acid or its salts even when the topical composition is stored at 4°C for one week, or the suppression of changes in appearance such as coloration even after storage at 50°C or 40°C.

[0101] In the method of the present invention, A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least one selected from the group consisting of low molecular weight betaine, organic acid salt, inorganic acid salt, basic amino acid, salt of basic amino acid, 3-O-ethyl ascorbic acid, and salt of 3-O-ethyl ascorbic acid, and (D) water are used in combination, and the content of ethoxydiglycol is less than 30% by mass and its content is the same as that used in the above-mentioned external composition. Furthermore, the product obtained by this method can be used in a known or commonly used dosage, once or several times a day depending on the purpose.

[0102] [Improved usability] In the present invention, it is also possible to improve the feeling of use of a topical composition containing at least one selected from the group consisting of (A) ascorbic acid and salts of ascorbic acid. In the present invention, by using at least one selected from the group consisting of (A) ascorbic acid and salts of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least one selected from the group consisting of low molecular weight betaine, organic acid salt, inorganic acid salt, basic amino acid, salt of basic amino acid, 3-O-ethyl ascorbic acid, and salt of 3-O-ethyl ascorbic acid, and (D) water in combination and making the content of ethoxydiglycol less than 30% by mass, the feeling of use can be good while containing ascorbic acid or its salt. In particular, a good feeling of use can be achieved while containing ascorbic acid or its salt at a high concentration (for example, 10% by mass or more, or 20% by mass or more).

[0103] In the present invention, in order to obtain a good feeling of use, (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) a diol having 3 carbon atoms, (C) at least one selected from the group consisting of low molecular weight betaine, organic acid salt, inorganic acid salt, basic amino acid, salt of basic amino acid, 3-O-ethyl ascorbic acid, and salt of 3-O-ethyl ascorbic acid, and (D) water are used in combination, and the content of ethoxydiglycol is less than 30% by mass and its content is the same as that used in the above-mentioned external composition. Here, the good feeling of use refers to at least one or all of the following when applied to the skin: feeling of penetration, little stickiness, relief of irritation, and smoothness of the skin. EXAMPLES

[0104] EXAMPLES Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to the following examples. In the tables, the unit of the amount of each component is % by mass.

[0105] The compositions for external use shown in the table were prepared according to a conventional method. Unless otherwise specified, the values ​​in the table represent mass %.

[0106] [Ascorbic acid precipitation inhibition confirmation test 1] The presence or absence of ascorbic acid precipitation was visually evaluated for topical compositions according to some examples and comparative examples of the present invention when the preparations were stored at low temperatures. Specifically, ascorbic acid was added to a mixed solution of various components according to the formulations (mass%) listed in various recipes, and the composition was prepared by heating and mixing at 60°C for 10 minutes to dissolve. The prepared composition was filled into a transparent glass bottle, left to stand at 4°C under light-shielded conditions, and stored for 1 week or 4 weeks, and each test solution was visually observed to determine the presence or absence of crystal precipitation.

[0107] <Evaluation criteria> ○: No precipitates were visible ×: Precipitates are visible to the naked eye

[0108] [Ascorbic acid precipitation inhibition confirmation test 2] In particular, in order to evaluate the stability of high-concentration ascorbic acid, the presence or absence of ascorbic acid precipitation was visually evaluated when the topical compositions according to the present invention and comparative examples were stored under harsh conditions below freezing point. Specifically, according to the formulations (mass%) listed in the various prescription tables, ascorbic acid was added to a mixed solution of various components, and the mixture was heated and mixed at 60°C for 10 minutes to dissolve the components, to prepare the compositions. The prepared compositions were filled into transparent glass bottles, left to stand at -8°C under light-shielded conditions, and stored for one week, and each test solution was visually observed to determine the presence or absence of crystal precipitation.

[0109] <Evaluation criteria> ○: No precipitates were visible ×: Precipitates are visible to the naked eye

[0110] [Color suppression confirmation test] The topical compositions according to the present invention and comparative examples were evaluated for the presence or absence of inhibition of coloring after storage at 40°C to 50°C by visual observation and a color difference meter. Specifically, ascorbic acid was added to a mixed solution of the seed ingredients according to the formulation (mass%) described in various recipes, and the mixture was heated and mixed at 60°C for 10 minutes to dissolve, to prepare a topical composition. The prepared topical composition was filled into a transparent glass bottle and left to stand in a thermostatic chamber at 40°C or 50°C for 1 to 4 weeks. The container was removed from the thermostatic chamber at each measurement period, and evaluated after being kept at a constant temperature of 25°C. The presence or absence and degree of coloring of each test solution was judged by visual observation and measurement using a color difference meter.

[0111] <Evaluation criteria> ○: No or slight color change △: Color change is observed but not significant ×: Significant change in color

[0112] For the color difference measurement, 1 mL of the test solution was placed in a glass cell (CM-A97, 2 mm thick), and the color difference was measured using a spectrophotometer CM-5 (Konica Minolta, Inc.) to measure the b value. The measured value was Δb* when purified water was used as the blank. The change in color difference was calculated using the following formula. (Change in color difference (Δb value)) = (Measurement value of test liquid after keeping warm (b value after accelerated test)) - (Measurement value of test liquid before keeping warm (b value before accelerated test)) The b value is used as an index of transparency. Therefore, the smaller the Δb value, the less coloring there is. The Δb* ratio is shown as the ratio of the values ​​for the Examples and Comparative Examples, with the color difference value of a specific topical composition in the table as the standard (1).

[0113] [Ascorbic acid percutaneous absorption test] The percutaneous absorbability of the topical composition according to some examples and comparative examples of the present invention was examined. By improving the percutaneous absorbability, ascorbic acid can penetrate into the skin, and the composition is expected to have a higher anti-aging effect. That is, in some cases, it is possible to exert the effect of ascorbic acid deep into the stratum corneum.

[0114] The percutaneous absorbability of ascorbic acid in the topical compositions prepared in the Examples and Comparative Examples was confirmed by measuring the evaluation by stratum corneum stripping.

[0115] Specifically, first, the amount of ascorbic acid in the stratum corneum of the components that had penetrated into the skin of the upper arm and forearm of a healthy human was confirmed by tape stripping. Healthy subjects who had given voluntary consent to participate in the study were used as subjects. Cotton impregnated with 750 μL of the topical composition of the Example or Comparative Example was applied to the inner part of the upper arm of the subject, 1.5 cm × 1.5 cm, and left to stand for 5 minutes. After removing the cotton, the sample remaining on the skin surface was removed with new cotton and left to stand for 30 minutes. This time was defined as the penetration time of the sample. Then, using a mending tape (manufactured by Sumitomo 3M Co., Ltd.), tape stripping was performed 7 times consecutively from the application site to peel off the keratinocytes, and all layers or 4 to 7 layers of the obtained tape were used as samples for measurement. The number of tape strips was set by confirming in a preliminary test that the necessary amount of keratinocytes was peeled off for each tape strip and that no inflammation or pain occurred after tape stripping.

[0116] The obtained measurement specimen was extracted with 1 mL of an extraction solvent consisting of a mixture (1:1:1000) of Tritonx-100 (MP Biomedicals), mercaptoethanol (Wako Pure Chemical Industries, Ltd.), and purified water. The amount of ascorbic acid permeated (μg / mL) from the extracted solution, from which foreign matter had been removed using a 0.45 μm syringe filter (GL Sciences, Inc.), was measured by HPLC. The amount of L-ascorbic acid contained in the solution was measured using an Agilent HPLC (mobile phase: acetonitrile / 0.02 M phosphoric acid solution (pH 3.0) (1:9), absorbance detection wavelength: 270 nm) equipped with a reverse phase column (CAPCELL PAK C18 SG120, Shiseido Co., Ltd.). The results were averaged to determine the amount of permeation (μg / cm2) for the measurement specimens taken from three locations on the arm of one subject. 2 ) were compared.

[0117] The detection of ascorbic acid by HPLC was carried out using an ultraviolet spectrophotometer at a wavelength of 270 nm with a reverse phase column (CAPCELL PAK C18 SG120, manufactured by Shiseido Co., Ltd.), and the content was calculated from the calibration curve.

[0118] [Usability test of topical compositions containing ascorbic acid] An appropriate amount (about 20 mg) of the topical compositions of the Examples and Comparative Examples was applied to the arm (inside of the forearm) and a usability test was conducted on three healthy subjects. In the usability test, the topical compositions were placed at room temperature where they are usually used, and the subjects were not informed of which composition they were using. Each composition was evaluated for its penetration, stickiness, irritation, and smoothness on the skin.

[0119] The evaluation results were scored as follows, and the average of the three scores was taken. 5 points: Very absorbent, not sticky, no irritation, smooth 4 points: Penetrates slightly, is not too sticky, does not irritate much, Slightly smooth 3 points: neither, neither, neither, Neither 2 points: Not absorbed well, a little sticky, some irritation felt, Not very smooth 1 point: Hardly penetrates, sticky, irritating, not smooth

[0120] (Examples 1 to 12 and Comparative Examples 1 to 6) The results of the ascorbic acid deposition inhibition confirmation test 1 and the transdermal absorbability test for the compositions of the Examples and Comparative Examples are shown in Tables 1 and 2. Note that N indicates the number of subjects.

[0121] The values ​​shown in the column "Transdermal Absorption Test Results" for Examples 1 to 3 are values ​​calculated as a ratio to Comparative Example 2, with the percutaneous absorption amount for Comparative Example 2 being set at 1. Ratio = (percutaneous absorption amount of any of the compositions of the Examples (μg / cm 2 ) / (percutaneous absorption amount of the composition of Comparative Example 2 (μg / cm 2 ) Furthermore, the values ​​shown in the percutaneous absorption columns for Comparative Examples 1, 3, and 4 are values ​​calculated by the ratio to Comparative Example 2, with the percutaneous absorption amount for Comparative Example 2 being set to 1. As shown below, Ratio = (percutaneous absorption amount of any of the compositions of Comparative Example, 3, or 4 (μg / cm 2 ) / (percutaneous absorption amount of the composition of Comparative Example 2 (μg / cm 2 )

[0122] [Table 1]

[0123] [Table 2]

[0124] It was confirmed that the compositions of the examples suppressed the precipitation of ascorbic acid even when stored at low temperature. Furthermore, it was surprisingly found that the compositions also had excellent transdermal absorbability.

[0125] The results of Ascorbic Acid Precipitation Inhibition Confirmation Test 1 are shown in Table 3.

[0126] [Table 3]

[0127] It is found that the topical compositions of the Examples can stably incorporate ascorbic acid even under low-temperature storage, as compared with the topical compositions of the Comparative Examples. This shows that the diol having three carbon atoms contributes to the inhibition of precipitation of ascorbic acid at low temperatures.

[0128] Next, Tables 4 to 5 show the results of stability tests (coloration inhibition confirmation tests) after storage at 40° C. for the topical compositions of the Examples and Comparative Examples.

[0129] [Table 4]

[0130] [Table 5]

[0131] The compositions of the Examples had a coloration suppressing effect even when stored under high temperature conditions, and exhibited excellent stability over a long period of time.

[0132] In other words, the topical compositions shown in the examples achieve both the properties of inhibiting precipitation of ascorbic acid and inhibiting discoloration of the topical composition, and further show excellent transdermal absorbability.

[0133] Furthermore, the concentration of ascorbic acid was changed to prepare the topical compositions of the examples shown in Table 6, and a transdermal absorbability confirmation test was carried out. The calculated ratios are shown in the table, assuming that the value of the test result, which was carried out by the same person using the same composition as in Example 1, was 1.

[0134] [Table 6]

[0135] In Examples 9 and 10, which have similar formulations to Example 1 except that the ascorbic acid concentration is 3%, good percutaneous absorption proportional to the ascorbic acid concentration was observed. Also, in Examples 11 and 12, which contain a high concentration of ascorbic acid of 25%, good percutaneous absorption was observed that was more than proportional to the ascorbic acid concentration of Example 1. From these results, it was found that the topical compositions of the Examples containing a diol having 3 carbon atoms have excellent percutaneous absorption properties.

[0136] (Examples 13 to 15, Comparative Examples 7 to 10) Furthermore, a topical composition containing ethoxydiglycol was prepared and subjected to percutaneous absorption test 1. The results are shown in the table below. [Table 7]

[0137] These results demonstrate that the topical composition containing a high concentration of propylene glycol has superior percutaneous absorption properties to the topical composition containing a high concentration of ethoxydiglycol.

[0138] Furthermore, a coloring inhibition confirmation test was carried out to verify the change in coloring inhibition effect depending on the amount of ethoxydiglycol. The results are shown in the table below.

[0139] [Table 8]

[0140] These results demonstrate that topical compositions containing less than 30% ethoxydiglycol exhibit superior discoloration inhibition effects compared to topical compositions containing a high concentration of ethoxydiglycol.

[0141] (Examples 16 to 45, Comparative Examples 11 to 16) Similarly, ascorbic acid precipitation inhibition confirmation test 1 and discoloration inhibition confirmation test were carried out for the topical compositions of further examples and comparative examples. The results are shown in the respective tables.

[0142] [Table 9]

[0143] These results demonstrate that the topical compositions of the examples have both excellent stability and discoloration suppression effects.

[0144] Similarly, for the topical compositions of further Examples and Comparative Examples, confirmation test 1 for inhibition of ascorbic acid deposition was carried out. The results are shown in the respective tables.

[0145] [Table 10]

[0146] [Table 11]

[0147] [Table 12]

[0148] [Table 13]

[0149] These results demonstrate that the topical compositions of the examples have excellent stability.

[0150] (Examples 46 to 61, Comparative Examples 17 to 46) Next, for the topical compositions of the Examples and Comparative Examples, confirmation test 1 for inhibition of ascorbic acid precipitation and confirmation test for inhibition of discoloration were carried out. The results are shown in Table 1. For Δb, Example 47 was set to 1.

[0151] [Table 14]

[0152] Next, instead of component (B), amino group or amide group-containing compounds other than low molecular weight betaine, such as tranexamic acid, nicotinamide, triethanolamine, lecithin hydroxide, or magnesium L-ascorbyl phosphate, were used to prepare topical compositions, and their stability was compared with that of the topical compositions of the examples. As a stability test, ascorbic acid precipitation inhibition confirmation test 1 was performed, and the results are shown in the table.

[0153] [Table 15]

[0154] Next, a topical composition was prepared using a different polyhydric alcohol instead of component (B), and the stability was compared with that of the topical composition of the Example. The results are shown in the table below.

[0155] [Table 16]

[0156] [Table 17]

[0157] As a result, it was found that the topical composition not containing component (B) exhibited precipitation of ascorbic acid and had stability problems.

[0158] Next, a composition for external use containing a high concentration of ascorbic acid was prepared, and its stability was compared with that of the composition for external use in the examples. As a stability test, ascorbic acid precipitation inhibition confirmation test 1 and 2 were performed, and the results are shown in the table.

[0159] [Table 18]

[0160] [Table 19]

[0161] It was also found that the topical compositions of the examples containing high concentrations of ascorbic acid suppressed precipitation of ascorbic acid over time and were excellent in stability.

[0162] (Examples 62 to 70, Comparative Examples 47 to 54) The results of the percutaneous absorption test for the topical compositions of the Examples and Comparative Examples are shown in the table below.

[0163] The numerical values ​​shown in the column of the results of the percutaneous absorption test of the topical composition of the Examples are values ​​calculated by the ratio to Comparative Example 47, with the percutaneous absorption amount of the Comparative Example being set at 1. Ratio = (percutaneous absorption amount of any of the compositions of the Examples (μg / cm 2 ) / (percutaneous absorption amount of the composition of Comparative Example 47 (μg / cm 2 ) Furthermore, these ratios, the values ​​shown in the column for percutaneous absorption of comparative examples, are values ​​calculated by taking the percutaneous absorption amount of Comparative Example 47 as 1 and calculating the ratio with each comparative example. Ratio = (percutaneous absorption amount of any of the compositions of the comparative examples (μg / cm 2 ) / (percutaneous absorption amount of the composition of Comparative Example 47 (μg / cm 2 )

[0164] [Table 20]

[0165] [Table 21]

[0166] These results demonstrate that the topical compositions of the Examples have superior transdermal absorbability compared to the topical compositions of the Comparative Examples.

[0167] Next, the results of evaluation of the topical compositions of the Examples and Comparative Examples with respect to the feeling of penetration, the presence or absence of stickiness, the presence or absence of irritation, and the smoothness of the skin are shown in the table below.

[0168] [Table 22]

[0169] [Table 23]

[0170] The topical compositions of the examples were shown to have an excellent feel when used. [Prescription example] Formulation examples are shown in the table below. All formulation examples can be suitably used for lotions, beauty essences, etc. All contents in the formulation examples are in mass %.

[0171] [Table 24] [Table 25]

Claims

1. (A) 10 to 30 mass% of at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid; (B) 24.5 to 85% by mass of a diol having 3 carbon atoms; (C) 0.01 to 4% by mass of at least one selected from the group consisting of 3-O-ethyl ascorbic acid and salts of 3-O-ethyl ascorbic acid; and (D) Water and wherein the content of ethoxydiglycol is less than 30% by mass.

2. The topical composition according to claim 1, wherein the (B) component is 25% by mass or more of the topical composition.

3. The composition for external use according to claim 1 or 2, wherein the amount of the component (D) is 0.01 to 20 parts by mass per 1 part by mass of the total content of the component (A).

4. The composition for external use according to any one of claims 1 to 3, wherein (B) is 1,3-propanediol or propylene glycol.

5. The composition for external use according to any one of claims 1 to 4, further comprising (E) a lower alcohol.

6. The composition for external use according to any one of claims 1 to 5, wherein the content of ethoxydiglycol in the composition for external use is 10% by mass or less.

7. The composition for external use according to any one of claims 1 to 6, which is substantially free of ethoxydiglycol.

8. The composition for external use according to any one of claims 1 to 7, which is a solubilized composition for external use having a transmittance of 85 to 100% at a wavelength of 700 nm.

9. The composition for external use according to any one of claims 1 to 8, which is for promoting percutaneous absorption of ascorbic acid.

10. A method for imparting stability to a topical composition containing (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, by using in combination 10 to 30% by mass of (A) at least one selected from the group consisting of ascorbic acid and salts of ascorbic acid, (B) 24.5 to 85% by mass of a diol having 3 carbon atoms, (C) 0.01 to 4% by mass of at least one selected from the group consisting of 3-O-ethyl ascorbic acid and salts of 3-O-ethyl ascorbic acid, and (D) water, with the content of ethoxydiglycol being less than 30% by mass.

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