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

Abstract

Provided is a composition for external use having excellent stability. A composition for external use, which contains (A) 1-40 mass% of at least one substance selected from the group consisting of ascorbic acid and a salt of ascorbic acid, (B) 20 mass% or more of a diol having 3 carbon atoms, (C) at least one substance selected from the group consisting of tocopherol, a salt of tocopherol and a derivative of tocopherol, and (D) water, is prepared. The mass ratio of component (D) / component (A) is 0.5-5.0, and the glycol ether is less than 20 mass%.

Description

[0001] This application is a divisional application of the invention patent application with Chinese application number 201980062314.5 (the invention name of the original application is "Topical composition containing ascorbic acid and / or its salt", and the application date of the original application is September 25, 2019) Technical Field

[0002] The present invention relates to a composition for external use containing ascorbic acid and / or a salt thereof. Background Art

[0003] Ascorbic acid is known to have various effects such as anti-inflammatory effect, acne improvement effect, whitening effect, anti-aging effect, antioxidant effect, cell activation effect by promoting the synthesis of biological components such as collagen, and effect of inhibiting cell damage and DNA damage of epidermal keratinocytes caused by ultraviolet rays. It is widely used as a skin external preparation in anticipation of these effects.

[0004] Ascorbic acid is easily oxidized in the presence of water such as in an aqueous solution, and therefore it is desired to reduce the amount of water in the preparation. However, a small amount of water cannot sufficiently solubilize ascorbic acid.

[0005] Therefore, several methods for stably solubilizing ascorbic acid in aqueous external skin preparations have been studied (for example, Patent Document 1: WO02 / 19972, Patent Document 2: WO00 / 78283, Patent Document 3: Japanese Patent Application Laid-Open No. 2002-348228, Patent Document 4: Japanese Patent Application Laid-Open No. 2005-225865).

[0006] Prior art literature

[0007] Patent Literature

[0008] Patent Document 1: WO02 / 19972

[0009] Patent Document 2: WO00 / 78283

[0010] Patent Document 3: Japanese Patent Application Publication No. 2002-348228

[0011] Patent Document 4: Japanese Patent Application Publication No. 2005-225865 Summary of the invention

[0012] An object of the present invention is to provide an external composition containing ascorbic acid having good stability.

[0013] Provided is a composition for external use containing ascorbic acid and / or a salt thereof, wherein the composition for external use can contain ascorbic acid and / or a salt thereof at various concentrations.

[0014] According to the studies conducted by the present inventors, it has been found that even if ascorbic acid and / or its salt is added at a predetermined concentration, it may be decomposed during storage.

[0015] The present inventors have conducted intensive studies to solve the problem and have found that a composition for external use having excellent stability of ascorbic acid or its salt can be obtained by containing (A) 1 to 40% by mass of at least one selected from ascorbic acid and its salts, (B) 20% by mass or more of a glycol having 3 carbon atoms, (C) at least one selected from tocopherol, its salts and tocopherol derivatives, and (D) water, with the mass ratio of component (D) to component (A) being 0.5 to 5.0 and the content of glycol ether being less than 20% by mass, thereby completing the present invention.

[0016] That is, the present invention provides the following external-use composition.

[0017] Item 1.

[0018] A composition for external use, comprising:

[0019] (A) 1 to 40% by mass of at least one selected from ascorbic acid and ascorbic acid salts,

[0020] (B) 20% by mass or more of a diol having 3 carbon atoms,

[0021] (C) at least one selected from the group consisting of tocopherol, a salt of tocopherol, and a derivative of tocopherol, and

[0022] (D) Water;

[0023] The mass ratio of component (D) / component (A) is 0.5 to 5.0, and the content of glycol ether is less than 20 mass %.

[0024] Item 2.

[0025] The composition for external use according to Item 1, further comprising a lower alcohol.

[0026] Item 3.

[0027] The composition for external use according to Item 1 or 2, wherein the component (B) contains 1,3-propylene glycol.

[0028] Item 4.

[0029] The composition for external use according to any one of items 1 to 3, wherein the component (B) accounts for 40% by mass or more.

[0030] Item 5.

[0031] The composition for external use according to any one of Items 1 to 4, wherein the content of the component (C) is 0.5% by mass or less.

[0032] Furthermore, the present invention provides the following method for imparting stability to a composition for external use.

[0033] Item 6.

[0034] A method for imparting stability to an external composition containing (A) at least one selected from ascorbic acid and a salt of ascorbic acid, wherein the external composition contains (A) 1 to 40% by mass of at least one selected from ascorbic acid and a salt of ascorbic acid, (B) 20% by mass or more of a diol having 3 carbon atoms, (C) at least one selected from tocopherol, a salt of tocopherol and a derivative of tocopherol, and (D) water, and the mass ratio of component (D) to component (A) is 0.5 to 5.0, and the content of glycol ether is less than 20% by mass, thereby imparting stability to the external composition.

[0035] According to the present invention, a composition for external use having excellent stability can be provided. DETAILED DESCRIPTION

[0036] In this specification, the unit "mass %" of content has the same meaning as "g / 100g".

[0037] The composition for external use of the present invention contains:

[0038] (A) 1 to 40% by mass of at least one selected from ascorbic acid and ascorbic acid salts,

[0039] (B) 20% by mass or more of a diol having 3 carbon atoms,

[0040] (C) at least one selected from the group consisting of tocopherol, a salt of tocopherol, and a derivative of tocopherol; and

[0041] (D) Water;

[0042] The mass ratio of component (D) / component (A) is 0.5 to 5.0, and the content of ethylene glycol ether is less than 20 mass %.

[0043] The composition for external use of the present invention is stable over a wide concentration range of (A) at least one selected from ascorbic acid and a salt of ascorbic acid and has high safety, and also has excellent feeling during use and transdermal absorbability.

[0044] [(A) at least one selected from ascorbic acid and a salt of ascorbic acid]

[0045] As the ascorbic acid used in the present invention, ascorbic acid commercially available as a component of an external skin preparation in the field of pharmaceuticals, quasi-drugs or cosmetics can be used, and these are generally L-forms.

[0046] Salts of ascorbic acid can also be used. Here, salts of ascorbic acid refer to pharmaceutically acceptable salts. There is no limitation, and examples thereof include salts with organic bases (e.g., salts formed with tertiary amines such as trimethylamine salts, triethylamine salts, monoethanolamine salts, triethanolamine salts, pyridinium salts, etc., alkaline ammonium salts such as arginine, etc.), and salts with inorganic bases (e.g., alkali metal salts such as ammonium salts, sodium salts, potassium salts, alkaline earth metal salts such as calcium salts, magnesium salts, aluminum salts, etc.). Particularly preferred salts of ascorbic acid are sodium salts and potassium salts. Specifically, sodium ascorbate, sodium ascorbyl monophosphate, sodium ascorbyl diphosphate, sodium ascorbyl triphosphate, sodium ascorbyl-2-sulfate, etc. can be cited.

[0047] In the present invention, ascorbic acid or a salt thereof may be used alone or in combination of two or more.

[0048] In the topical composition of the present invention, the total content of the (A) component relative to the total amount of the topical composition can be appropriately set according to the balance with other ingredients. Relative to the total amount of the topical composition, the total content of the (A) component is 1% by mass or more, preferably 2% by mass or more, and further more preferably 3% by mass or more. Relative to the total amount of the topical composition, the total content of the (A) component is 40% by mass or less, preferably 30% by mass or less, and further more preferably 25% by mass or less. Relative to the total amount of the topical composition, the total content of the (A) component is 1% by mass to 40% by mass, preferably 2% by mass to 30% by mass, and further preferably 3% by mass to 25% by mass.

[0049] [(B) Diol having 3 carbon atoms]

[0050] The diol with 3 carbon atoms used in the present invention is not particularly limited as long as it is a diol with 3 carbon atoms used as a component of a skin external preparation in the field of medicines, quasi-drugs or cosmetics. In addition, such a diol with 3 carbon atoms can also be used directly as a commercial product. As a diol with 3 carbon atoms, there is no limitation, for example, 1,3-propylene glycol (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, alias: 1,2-propylene glycol) can be exemplified, and one type can be used or a combination thereof can be used appropriately. From the viewpoint of alleviating irritation to the skin, improving the feeling of use, and inhibiting the coloring of the preparation, combining 1,3-propylene glycol and propylene glycol is also one of the preferred methods. As component (B), it is more preferred to contain at least 1,3-propylene glycol.

[0051] In the external composition of the present invention, the total content of the component (B) relative to the total amount of the external composition is not particularly limited, and is 20% by weight or more, preferably 25% by weight or more, more preferably 30% by weight or more, further preferably 35% by weight or more, and further more preferably 40% by weight or more.

[0052] The total content of the component (B) based on the total amount of the external composition is preferably 90% by mass or less, more preferably 85% by mass or less, and even more preferably 80% by mass or less.

[0053] The total content of the component (B) based on the total amount of the external composition is not particularly limited, but is preferably 20 to 90% by mass, more preferably 25 to 85% by mass, further preferably 30 to 80% by mass, and further more preferably 40 to 80% by mass.

[0054] In the external composition of the present invention, the ratio of the amount of component (B) to component (A) is not particularly limited, but is preferably 1 to 300 parts by mass, more preferably 1 to 100 parts by mass, and even more preferably 1 to 30 parts by mass, relative to 1 part by mass of the total content of component (A).

[0055] [(C) at least one selected from the group consisting of tocopherol, a salt of tocopherol, and a derivative of tocopherol]

[0056] As (C) used in the present invention, at least one selected from tocopherol, salts of tocopherol and derivatives of tocopherol (vitamin E class), compounds commonly used as components of skin external preparations in the fields of pharmaceuticals, quasi-drugs or cosmetics can be used, and can be any of the d-body, l-body or dl-body, and can be any of the structures of α, β, γ, and δ. (C) At least one selected from tocopherol, salts of tocopherol and derivatives of tocopherol is not particularly limited. As tocopherol, for example, d-α-tocopherol, d-β-tocopherol, d-γ-tocopherol and d-δ-tocopherol, l-α-tocopherol, l-β-tocopherol, l-γ-tocopherol, l-δ-tocopherol, dl-α-tocopherol, dl-β-tocopherol, dl-γ-tocopherol, dl-δ-tocopherol, etc. as mixtures thereof can be cited. As derivatives of tocopherol, there is no limitation, and esters of tocopherol are preferred. In addition, as the derivative of tocopherol, in particular, one selected from tocopherol acetate, tocopherol nicotinate or its salt, tocopherol succinate or its salt, tocopherol linolenate, tocopherol phosphate or its salt, tocopherol (linoleic acid / oleic acid) ester and tocotrienols, etc. can be exemplified. Among them, tocopherol or tocopherol acetate which can be any one of d-body, l-body or dl-body and can be any one of α, β, γ, δ structures is particularly preferred.

[0057] In addition, these may be naturally derived or synthesized, or commercially available products may be used as they are.

[0058] These vitamin E compounds can be used alone or in combination of two or more.

[0059] These vitamins E contribute to higher stability of the external composition of the present invention.

[0060] In the topical composition of the present invention, the total content of the component (C) relative to the total amount of the topical composition is not particularly limited, and is preferably 0.00001% by mass or more, and more preferably 0.0001% by mass or more. Relative to the total amount of the topical composition, the total content of the component (C) is preferably 10% by mass or less, and more preferably 5% by mass or less. Relative to the total amount of the topical composition, the content of the component (C) is preferably 0.00001 to 10% by mass, and more preferably 0.0001 to 5% by mass.

[0061] [(D) Water]

[0062] 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 to 60% by mass, more preferably 0.01 to 50% by mass, further preferably 0.1 to 40% by mass, and most preferably 1 to 30% by mass relative to the composition for external use.

[0063] In the external composition of the present invention, the ratio of the component (D) to the component (A) is 0.5 to 5.0 parts by mass, more preferably 0.5 to 4.0 parts by mass, based on 1 part by mass of the total content of the component (A).

[0064] [Ethylene glycol ether]

[0065] In the present invention, mainly from the viewpoint of improving stability, glycol ethers such as ethoxydiglycol are not contained, or even if contained, they are less than 20% by mass. As the glycol ethers less than 20% by mass contained in the external composition, there is no particular limitation as long as the glycol ethers used as components of skin external preparations in the fields of pharmaceuticals, quasi-drugs or cosmetics are used. Here, as glycol ethers, except ethoxydiglycol, any glycol ethers used as components of skin external preparations in the fields of quasi-drugs or cosmetics, and dissolving more than 10g of glycol ether relative to 100g of water, can be exemplified. Glycol ethers with a degree of polymerization of less than 2 can be exemplified. 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 and the like can be exemplified. In addition, 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 are typical examples. In particular, 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 are typical examples.

[0066] These glycol ethers may be used alone or in combination of two or more.

[0067] In the external composition of the present invention, the total content of glycol ethers including ethoxydiglycol relative to the total amount of the external composition is less than 20% by mass, preferably 15% by mass or less, more preferably 10% by mass or less, and the external composition may not contain glycol ethers.

[0068] The total content of glycol ethers including ethoxydiglycol is preferably 0% or more and less than 20% by mass, more preferably 0 to 15% by mass, and even more preferably about 0 to 10% by mass.

[0069] In the external composition of the present invention, the ratio of the amount of the glycol ether component to the component (A) is preferably 0 to 10 parts by mass, more preferably 0 to 5 parts by mass, relative to 1 part by mass of the total content of the component (A). Alternatively, it may be 0.001 to 20 parts by mass, or 0.01 to 10 parts by mass, depending on circumstances.

[0070] The external composition of the present invention can also be made into an external composition with excellent stability by containing (A), (B), (C) and (D) and specifying the total content of the glycol ether.

[0071] [(E) Lower alcohol]

[0072] The external composition of the present invention may optionally contain (E) a lower alcohol in addition to the above-mentioned components (A), (B), (C) and (D) and glycol ethers such as ethoxydiglycol when contained, from the viewpoint of improving the feeling during use, stability and promoting percutaneous absorption, unless the effects of the present invention are impaired.

[0073] The lower alcohol used in the present invention is not particularly limited as long as it is a lower alcohol used as a component of a skin external preparation in the field of pharmaceuticals, quasi-drugs or cosmetics. In this specification, "lower alcohol" refers to C1-C6 alcohol. Among them, C1-C3 alcohol can be particularly preferably used. As such examples, methanol, ethanol, n-propanol, isopropanol, etc. can be cited.

[0074] In the composition for external use of the present invention, the total content of the component (E), when contained, is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, based on the total amount of the composition for external use.

[0075] The total content of the component (E) is preferably 25% by mass or less, more preferably 20% by mass or less.

[0076] The total content of the component (E) is preferably 0.001 to 30% by mass, more preferably 0.1 to 25% by mass, further preferably 0.5 to 20% by mass, and still more preferably 1 to 20% by mass.

[0077] In the external composition of the present invention, the ratio of the amount of the component (E) to the component (A) is preferably 0.01 to 10 parts by mass based on 1 part by mass of the total content of the component (A).

[0078] [Polyol]

[0079] The external composition of the present invention may contain a polyhydric alcohol in addition to the above-mentioned components (A), (B), (C), (D) and glycol ethers such as ethoxydiglycol in a certain amount unless the effects of the present invention are impaired.

[0080] As the polyol used in the present invention, there is no particular limitation as long as it is a polyol used as a component of a skin external preparation in the field of pharmaceuticals, quasi-drugs or cosmetics. The polyol is not limited, and sometimes it is added for moisturizing or as a solubilizing agent. Specifically, glycerol, diglycerol, dipropylene glycol, 1,3-butylene glycol, 3-methyl-1,3-butylene glycol, etc. can be cited. Preferably, 1,3-butylene glycol or dipropylene glycol.

[0081] Here, the total content of the polyol other than the component (B), when contained, is preferably about 0.001 to 60% by mass, more preferably 0.01 to 50% by mass, further preferably 0.1 to 40% by mass, and still further preferably about 0.5 to 30% by mass.

[0082] [pH adjuster having amine or amino group]

[0083] In the topical composition of the present invention, from the viewpoint of improving the feeling of use, stability and promoting percutaneous absorption, as long as the effect of the present invention is not hindered, in addition to the above-mentioned (A), (B), (C) and (D) components and glycol ethers such as ethoxydiglycol when contained, a pH adjusting agent with amine or amino group may also be contained. As the pH adjusting agent with amine that can be used in the present invention, a compound commonly used as a component of a skin topical preparation in the field of pharmaceuticals, quasi-drugs or cosmetics can be used. As the pH adjusting agent with amine or amino group, it is not particularly limited, for example, aspartic acid, ε-aminocaproic acid, glutamic acid, aminoethylsulfonic acid, monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, lysine, low molecular betaine, etc. can be exemplified. Among them, low molecular betaine is particularly preferred.

[0084] In the present invention, low molecular weight betaine refers to a substance that forms zwitterions in a molecule with a molecular weight of 200 or less, and specifically, quaternary ammonium bases, quaternary Onium bases, tertiary sulfonium bases, etc., which hardly show properties as surfactants.

[0085] Specific examples thereof include trimethylglycine, triethylglycine, tripropylglycine, triisopropylglycine, trimethyl-β-alanine, trimethyl-γ-aminobutyric acid, and trimethylglycine is preferred.

[0086] Furthermore, these low molecular weight betaines may be substituted. Specific examples thereof include N,N,N-trimethylalanine, N,N,N-triethylalanine, N,N,N-triisopropylalanine, N,N,N-trimethylmethylalanine, L-carnitine, acetylcarnitine, and the like, and carnitine is preferred.

[0087] Furthermore, these may be synthesized, or commercially available products may be used as they are.

[0088] These low molecular weight betaines may be used alone or in combination of two or more.

[0089] A pH adjuster having an amine or an amino group, such as low-molecular-weight betaine, can be used when it is desired to improve the transdermal absorbability of the external composition of the present invention.

[0090] In the topical composition of the present invention, the total content of the pH adjusting agent having an amine or an amino group relative to the total amount of the topical composition is not particularly limited, and is preferably 0.01% by mass or more, and more preferably 0.05% by mass or more. Relative to the total amount of the topical composition, the total content of the pH adjusting agent having an amine or an amino group is preferably 25% by mass or less, and more preferably 20% by mass or less. Relative to the total amount of the topical composition, the content of the pH adjusting agent having an amine or an amino group is preferably 0.01% by mass to 25% by mass, and more preferably 0.05% by mass to 20% by mass.

[0091] In the external composition of the present invention, the ratio of the amount of the pH adjuster having an amine or amino group to the component (A) is not particularly limited, but is preferably 0.00001 to 20 parts by mass, more preferably 0.0001 to 20 parts by mass, further preferably 0.001 to 10 parts by mass, further preferably 0.0025 to 5 parts by mass, and most preferably 0.01 to 3 parts by mass, relative to 1 part by mass of the total content of the component (A).

[0092] [3-O-ethyl ascorbic acid]

[0093] The external composition of the present invention may contain 3-O-ethyl ascorbic acid or a salt thereof in addition to the above (A), (B), (C), (D) and ethoxydiglycol in an amount less than a certain amount, unless the effects of the present invention are impaired.

[0094] 3-O-ethyl ascorbic acid can be synthesized by ethoxylating the hydroxyl group at position 3 of ascorbic acid (for example, according to the known method described in Japanese Unexamined Patent Publication No. 8-134055). 3-O-ethyl ascorbic acid can also be directly used as a commercial product. There is no limitation on the commercial products, for example, in addition to "VC ETHYL" manufactured by Nippon Seika, products manufactured by Junsei Chemical Co., Ltd. can also be exemplified.

[0095] 3-O-Ethyl ascorbic acid contributes to the stability of the composition for external use of the present invention.

[0096] 3-O-ethyl ascorbic acid can also be used in the form of a salt. Here, the salt of 3-O-ethyl ascorbic acid refers to a pharmaceutically acceptable salt. There is no limitation, for example, salts with organic bases (for example, salts with tertiary amines such as trimethylamine salts, triethylamine salts, monoethanolamine salts, triethanolamine salts, pyridinium salts, etc., alkaline ammonium salts such as arginine, etc.), salts with inorganic bases (for example, alkali metal salts such as ammonium salts, sodium salts, potassium salts, alkaline earth metal salts such as calcium salts, magnesium salts, aluminum salts, etc.), etc. Particularly preferred salts of 3-O-ethyl ascorbic acid are sodium salts and potassium salts.

[0097] In the present invention, 3-O-ethyl ascorbic acid or a salt thereof may be used alone or in combination of two or more.

[0098] In the topical composition of the present invention, the total content of 3-O-ethyl ascorbic acid or its salt relative to the total amount of the topical composition can be appropriately set according to the balance with other ingredients. Relative to the total amount of the topical composition, preferably 0.005 mass % or more, more preferably 0.01 mass % or more, further preferably 0.02 mass % or more, more preferably 0.05 mass % or more, most preferably 0.1 mass % or more. In addition, relative to the total amount of the topical composition, the total content of 3-O-ethyl ascorbic acid or its salt is preferably 10 mass % or less, more preferably 5 mass % or less, further preferably 3 mass % or less, more preferably 2 mass % or less. Relative to the total amount of the topical composition, the total content of 3-O-ethyl ascorbic acid or its salt is preferably 0.005-10 mass %, more preferably 0.01-5 mass %, further preferably 0.02-3 mass %, further more preferably 0.05-2 mass %.

[0099] In the external composition of the present invention, the ratio of the amount of 3-O-ethyl ascorbic acid or a salt thereof to component (A) is such that the total content of 3-O-ethyl ascorbic acid or a salt thereof is preferably 0.0001 to 100 parts by mass, more preferably 0.001 to 100 parts by mass, further preferably 0.005 to 10 parts by mass, and most preferably 0.005 to 1 part by mass, relative to 1 part by mass of the total content of component (A).

[0100] [Surfactant]

[0101] The topical composition of the present invention may contain a surfactant as long as it does not hinder the effect of the present invention. When containing a surfactant, a surfactant having an HLB of generally 8 to 20, preferably 8 to 18, more preferably 9 to 16, and further preferably 10 to 15 can be used. Such a surfactant can contribute to the stabilization of component (C). For example, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 80, polyoxyethylene polyoxypropylene decyl tetradecyl ether, polyoxyethylene (20) polyoxypropylene (4) hexadecyl ether, PEG-8 glyceryl isostearate, polyoxyethylene sorbitan monolaurate (20E.O.), polyoxyethylene sorbitan isostearate (20E.O.), polyoxyethylene sorbitan stearate (20E.O.), polyglyceryl-10 coconut oil fatty acid ester, polyglyceryl-3 coconut oil fatty acid ester, PEG-7 glyceryl coconut oil fatty acid ester, polyglyceryl -10 dioleate, polyglyceryl-10 diisostearate, PEG-40 glyceryl triisostearate, PEG-40 glyceryl isostearate, polyglyceryl-10 trilaurate, hexaglyceryl tricaprylate, polyglyceryl laurate, polyglyceryl myristate, polyoxyethylene lauryl ether, etc., particularly preferably polyoxyethylene polyoxypropylene decyl tetradecyl ether, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene hydrogenated castor oil 80, polyoxyethylene sorbitan isostearate (20E.O.), polyoxyethylene sorbitan monolaurate (20E.O.), and polyglyceryl laurate.

[0102] In the external composition of the present invention, the total content of the surfactant relative to the total amount of the external composition can be appropriately set according to the balance with other components. The total content of the surfactant relative to the total amount of the external composition is preferably 0.01 to 10% by mass, more preferably 0.05 to 5% by mass, and further preferably 0.1 to 3% by mass.

[0103] [Other ingredients]

[0104] In the topical composition of the present invention, except for the above-mentioned (A), (B), (C), (D) and the ethoxydiglycol less than a certain amount when containing, for the various effects of strengthening or supplementing ascorbic acid and for the addition of other useful effects, various components such as whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activation ingredients, astringent ingredients, antioxidant ingredients, acne-improving ingredients, anti-aging ingredients, collagen and other biological component synthesis promoting ingredients, blood circulation promoting ingredients, moisturizing ingredients, anti-aging ingredients, etc. can also be further combined with one or more than two kinds of ingredients. It is preferably one or more than two kinds of ingredients in whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activation ingredients, astringent ingredients, antioxidant ingredients, anti-aging ingredients or moisturizing ingredients. As a particularly preferred combination in the combination of these ingredients, a combination with a whitening ingredient, a combination with a whitening ingredient and an antioxidant ingredient, each combination with an antioxidant ingredient, a combination with an anti-aging ingredient, and each combination with a whitening ingredient and an anti-aging ingredient can be cited. There are no particular limitations on these components as long as they are components that have been used in the past and will be used in the future as components of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics, and any component can be appropriately selected and used.

[0105] In addition to the above-mentioned components, the external composition of the present invention may further contain a solubilizing component, oils, sugars or a percutaneous absorption promoting component. In particular, by containing a solubilizing component or oils, the stability, effectiveness and feel of ascorbic acid in an aqueous solvent can be further improved.

[0106] The external composition of the present invention may be formulated as necessary with various components commonly used as external preparations in the fields of pharmaceuticals, quasi-drugs or cosmetics, such as amino acids, irritation reducing agents, thickeners, preservatives, ultraviolet protection agents, colorants, dispersants, additional pH adjusters, fragrances, etc., within the range of quantity and quality that do not impair the quality of appearance stability, viscosity, and the effects of the present invention. It should be noted that these components may be formulated alone or in combination of two or more.

[0107] The topical composition of the present invention comprises (A) at least one selected from ascorbic acid and ascorbic acid salts 1 to 40% by mass, (B) 20% or more of a glycol having 3 carbon atoms, (C) at least one selected from tocopherol, salts of tocopherol and derivatives of tocopherol and (D) water, so that the mass ratio of component (D) / component (A) is 0.5 to 5.0, and ethylene glycol ether is less than 20% by mass, and each of the above-mentioned arbitrary components is mixed as required, and other solvents, bases of commonly used topical agents, etc. are further mixed as required, so that various desired forms such as paste, mousse, gel, liquid, emulsion, cream, sheet (supporting substrate), aerosol, and spray can be prepared. They can be manufactured using the usual methods in the art.

[0108] The topical composition of the present invention is particularly preferably a transparent or translucent composition in which ascorbic acid and / or its salts are solubilized. Here, "solubilization" is defined as follows. That is, for example, it refers to a transmittance of 80 to 100%, preferably 85 to 100%, and more preferably 90 to 100% at a wavelength of 700 nm by ultraviolet visible absorbance determination, using a spectrophotometer or a photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation). Here, the transmittance of water is set to 100%. The solubilized composition of the present invention presents a transparent or translucent appearance. In more detail, the transmittance determination method is based on the method described in the 16th edition of the revised Japanese Pharmacopoeia [B] Conventional Test Method 2. Physical Test Method Spectrophotometry 2.24 Ultraviolet Visible Absorbance Determination Method.

[0109] [Viscosity]

[0110] The topical composition of the present invention can be prepared into a composition having a desired moderate viscosity, especially when using a topical composition for application to the skin. The viscosity of the topical composition of the present invention is not particularly limited. For example, the viscosity when measured at 25°C using an E-type viscometer is usually about 1 to 300 mPa·s, preferably about 1 to 200 mPa·s, more preferably about 1 to 100 mPa·s, and most preferably about 1 to 50 mPa·s. In more detail, the viscosity measurement method is based on the method described in the 16th revised edition of the Japanese Pharmacopoeia [B] Conventional 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 Rotational Viscometer (Cone-Plate Viscometer).

[0111] [pH]

[0112] The external composition of the present invention generally has a liquid property of pH 1 to 8, but from the viewpoints of the stability of ascorbic acid, low irritation to the skin and mucous membranes, and good feeling on the skin, it is preferably pH 2 to 7, more preferably pH 2 to 6, further preferably pH 2 to 5.0, and most preferably pH 2 to 4.5. It is preferably in the acidic region.

[0113] [use]

[0114] The external composition of the present invention is particularly effective as a whitening agent, an anti-derivative agent, and an anti-aging agent, for example, it has the effect of preventing or treating acne and anti-oxidation. In addition, by being applied to the skin, it can sometimes play the effect of improving the transparency of the skin, keeping it moist, making the skin texture uniform, and suppressing roughness. In addition, it can sometimes play the effect of making pores less noticeable and moisturizing the whole skin. In addition, it can also be used for the prevention and treatment of acne.

[0115] The external composition of the present invention can be, for example, a basic cosmetic such as a beauty serum, a toner, a sunscreen, an emulsion, a cream, an emulsion, an oil, and a facial mask; a beauty cosmetic such as a foundation, a lipstick, a lip balm, a mascara, an eye shadow, an eyeliner, an eyebrow pencil, and a nail polish; a cleaning agent such as a facial cleanser, a facial cleanser, and a body cleanser; various external compositions in the field of cosmetics, external medicines, or external quasi-drugs such as an anti-armpit odor agent, an tinea pedis therapeutic agent, an antipruritic agent, a wound therapeutic agent, a cleaning agent, a cleaning agent, an anti-inflammatory analgesic agent, an acne therapeutic agent, a hemorrhoid agent, a bactericidal disinfectant, a whitening agent, and an ultraviolet protective agent. From the perspective of the effect on the skin, the present invention is preferably used for products for the skin such as skin external preparations (preparations for the skin). The composition of the present invention can be used once to multiple times a day according to the use, etc., according to the known or commonly used usage and dosage.

[0116] [Stabilization method]

[0117] In addition, the present invention also includes a stabilization method of (A) at least one selected from ascorbic acid and ascorbic acid salts. In the present invention, according to the stabilization method of ascorbic acid, by containing (A) at least one selected from ascorbic acid and ascorbic acid salts 1 to 40% by mass, (B) 20% or more of a glycol having 3 carbon atoms, (C) at least one selected from tocopherol, tocopherol salts and tocopherol derivatives, and (D) water, and making the mass ratio of (D) component / (A) component 0.5 to 5.0, and making the glycol ether less than 20% by mass, it is possible to prepare a stable preparation while containing ascorbic acid. In particular, a stable preparation can be prepared while containing a high concentration (e.g., 15% or more or 20% or more) of ascorbic acid. That is, the present invention relates to a method for imparting stability to an external composition containing (A) at least one selected from ascorbic acid and a salt of ascorbic acid, by making the external composition contain (A) at least one selected from ascorbic acid and a salt of ascorbic acid 1 to 40% by mass, (B) more than 20% by mass of a glycol having 3 carbon atoms, (C) at least one selected from tocopherol, a salt of tocopherol and a derivative of tocopherol, and (D) water, and making the mass ratio of component (D) / component (A) 0.5 to 5.0, and making the glycol ether less than 20% by mass, thereby imparting stability to the external composition. Here, stabilization is not limited, for example, it means that stability can be guaranteed at high temperature or low temperature. Specifically, it means that the concentration of ascorbic acid is suppressed when stored at 50°C or 40°C or stored at room temperature.

[0118] In the method of the present invention,

[0119] The composition comprises (A) 1 to 40% by mass of at least one selected from ascorbic acid and its salts, (B) 20% by mass or more of a glycol having 3 carbon atoms, (C) at least one selected from tocopherol, a salt of tocopherol and a derivative of tocopherol, and (D) water, wherein the mass ratio of component (D) to component (A) is 0.5 to 5.0, and the content of glycol ether is less than 20% by mass, and the content thereof is the same as that used in the above-mentioned external composition.

[0120] The present invention includes the following aspects.

[0121] [1] A composition for external use, comprising:

[0122] (A) 1 to 40% by mass of at least one selected from ascorbic acid and ascorbic acid salts,

[0123] (B) 20% by mass or more of a diol having 3 carbon atoms,

[0124] (C) at least one selected from the group consisting of tocopherol, a salt of tocopherol, and a derivative of tocopherol, and

[0125] (D) Water,

[0126] The mass ratio of component (D) / component (A) is 0.5 to 5.0, and the content of glycol ether is less than 20 mass %.

[0127] [2] The composition for external use according to [1], further comprising a lower alcohol.

[0128] [3] The composition for external use according to [2], wherein the lower alcohol is ethanol.

[0129] [4] The composition for external use according to any one of [2] to [3], wherein the content of the lower alcohol is 0.001 to 30% by mass.

[0130] [5] The composition for external use according to any one of [1] to [4], wherein the component (B) contains 1,3-propylene glycol.

[0131] [6] The composition for external use according to any one of [1] to [5], wherein the content of component (B) is 40% by mass or more.

[0132] [7] The composition for external use according to any one of [1] to [6], wherein the content of component (C) is 0.5% by mass or less.

[0133] [8] The composition for external use according to any one of [1] to [7], wherein the amount of ethoxydiglycol ether is less than 10% by mass.

[0134] Furthermore, the present invention provides the following method for imparting stability to a composition for external use.

[0135] [9] A method for imparting stability to a composition for external use containing (A) at least one selected from ascorbic acid and a salt of ascorbic acid, the composition comprising (A) 1 to 40% by mass of at least one selected from ascorbic acid and a salt of ascorbic acid, (B) 20% by mass or more of a diol having 3 carbon atoms, (C) at least one selected from tocopherol, a salt of tocopherol and a derivative of tocopherol, and (D) water, wherein the mass ratio of component (D) to component (A) is 0.5 to 5.0, and the content of glycol ether is less than 20% by mass, thereby imparting stability to the composition for external use.

[0136]

[10] The method according to [9], wherein the external composition further contains a lower alcohol.

[0137]

[11] The method according to

[10] , wherein the lower alcohol is ethanol.

[0138]

[12] The method according to any one of

[10] or

[11] , wherein the content of the lower alcohol is 0.001 to 30% by mass.

[0139]

[13] The method according to any one of [9] to

[12] , wherein the component (B) of the external composition contains 1,3-propylene glycol.

[0140]

[14] The method according to any one of [9] to

[13] , wherein the component (B) in the external composition is 40% by mass or more.

[0141]

[15] The method according to any one of [9] to

[14] , wherein the content of component (C) in the external composition is 0.5% by mass or less.

[0142]

[16] The composition for external use according to any one of [1] to [7], wherein the amount of ethoxydiglycol ether contained in the composition for external use is less than 10% by mass.

[0143] Example

[0144] Next, the present invention will be specifically described by way of examples, but the present invention is not limited to the following examples. It should be noted that the unit of the amount of each component in the table is mass %.

[0145] The external-use compositions having the compositions shown in Tables 1 to 3 were prepared by conventional methods. Unless otherwise specified, the numerical values ​​in the tables represent mass %.

[0146] [Ascorbic acid stability test]

[0147] 15 g of each of the external-use compositions of the examples and comparative examples were filled in glass property bottles capable of accommodating 20 g, and allowed to stand in respective constant temperature and humidity machines. After 2 or 4 weeks, the containers were taken out of the constant temperature and humidity machine, kept constant at 25° C., and the change in the amount of ascorbic acid was evaluated.

[0148] Ascorbic acid was detected by HPLC using an ultraviolet spectrophotometer at a wavelength of 270 nm using a reverse phase column (Inertsil ODS-3, manufactured by GL Sciences Co., Ltd.), and the content was calculated.

[0149] The results of the ascorbic acid stability test of the compositions of the examples and comparative examples are shown in Tables 1 to 3. For each formulation, the change in the amount of ascorbic acid is expressed as "improvement rate" compared to the same formulation, except for the presence or absence of tocopherol. The improvement rate is calculated as shown in the following formula. For each formulation, the change in the amount of ascorbic acid is expressed as "improvement rate" compared to the same formulation, except for the presence or absence of tocopherol. It should be noted that the amount of ascorbic acid (mass %) after the test is implemented is set to "residual rate". The improvement rate is calculated as shown in the following formula.

[0150] Reduction rate 1 = (100 - residual rate of ascorbic acid in the composition without tocopherol)

[0151] Reduction rate 2 = (100 - residual rate of ascorbic acid in the composition containing tocopherol)

[0152] Improvement rate = {(reduction rate 1 - reduction rate 2) / reduction rate 1} × 100 (%)

[0153] Here, the compositions differing only in the absence of tocopherol were used for calculation of the reduction rate 1 and the reduction rate 2. However, the composition not containing tocopherol was supplemented with the polyol having the largest blending amount.

[0154] [Table 1]

[0155]

[0156] As shown in Table 1, it can be seen that the formula with 1,3-propylene glycol (hereinafter, PD) improves the decomposition of ascorbic acid (VC) by adding tocopherol (VE) (Examples 2 and 3). It should be noted that this improvement is independent of the concentration of VC or VE. In addition, it can be seen that the same improvement is also achieved in the formula with 35.5% by weight or more of PG (Examples 4 and 5). The same trend is also observed in the formula of Example 1 in which PD and PG are added.

[0157] [Table 2]

[0158]

[0159] As shown in Table 2, it can be seen that the formulations containing high concentrations of PD (Examples 6 and 7) improved the decomposition of ascorbic acid by adding d-δ-tocopherol. However, in the formulations containing low concentrations of polyols other than PD, PG, and formulations containing a large amount of water, the improvement rate was slow, or the decomposition of ascorbic acid was accelerated by adding d-δ-tocopherol (Comparative Examples 4 to 7).

[0160] [Table 3]

[0161] Stability of ascorbic acid (50℃2w)

[0162] (quality%))

[0163]

[0164] Here, the improvement rate (%) of ascorbic acid concentration in Table 3 is [{(100-residual rate of ascorbic acid in the composition of Comparative Example 8)-(100-residual rate of ascorbic acid in the composition of each example)} / (100-residual rate of ascorbic acid in the composition of Comparative Example 8)]×100.

[0165] As shown in Table 3, the formulations containing PD and PG respectively improved the decreased VC content in the formulation containing DPG (Examples 8 and 9).

[0166] [Formulation Example]

[0167] The formulation examples are shown in the following Table 4. The formulation examples are all beauty serums, and the contents in the formulation examples are all mass %.

[0168] [Table 4]

[0169]

Claims

1. A composition for external use, comprising: (A) 1 to 40% by mass of at least one selected from ascorbic acid and ascorbic acid salts, (B) 20% by mass or more of a diol having 3 carbon atoms, (C) at least one selected from the group consisting of tocopherol, a salt of tocopherol, and a derivative of tocopherol, and (D) Water; The mass ratio of component (D) / component (A) is 0.5 to 5.0, and the content of glycol ether is less than 20 mass %.

2. The composition for external use according to claim 1, wherein It further contains a lower alcohol.

3. The external use composition according to claim 1 or 2, wherein The component (B) contains 1,3-propylene glycol.

4. The composition for external use according to any one of claims 1 to 3, wherein The component (B) is 40% by mass or more.

5. The composition for external use according to any one of claims 1 to 4, wherein The content of the component (C) is 0.5 mass % or less.

6. A method for imparting stability to a composition for external use containing (A) at least one selected from ascorbic acid and a salt of ascorbic acid, the composition for external use containing (A) 1 to 40% by mass of at least one selected from ascorbic acid and a salt of ascorbic acid, (B) 20% by mass or more of a glycol having 3 carbon atoms, (C) at least one selected from tocopherol, a salt of tocopherol and a derivative of tocopherol, and (D) water, wherein the mass ratio of component (D) to component (A) is 0.5 to 5.0, and the content of glycol ether is less than 20% by mass, thereby imparting stability to the composition for external use.

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