Ascorbic acid and / or external composition containing its salt

Abstract

The present invention provides an external composition with excellent stability and feel in use. The external composition is prepared as follows: it contains (A) at least one selected from ascorbic acid and salts of ascorbic acid, 10% by mass or less, (B) a diol with three carbon atoms, 30% by mass or more, and (C) water, 20% by mass or less; and the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less. Alternatively, the external composition is prepared as follows: it contains (A) at least one selected from ascorbic acid and salts of ascorbic acid, 10 to 25% by weight, (B) a diol with three carbon atoms, which accounts for 30 to 90% by mass in the components other than (A) and (C), and (C) water, and the content of ethoxydiglycol is less than 30% by mass, (C) / (A)=0.2 to 5, and the pH is 2.0 to 6.0.

Description

Technical Field

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

[0002] Ascorbic acid is known to exert 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, and is widely used as a skin external preparation in anticipation of these effects.

[0003] Several methods have been studied to stably solubilize ascorbic acid in aqueous external skin preparations (e.g., 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).

[0004] Patent Document 1: WO02 / 19972

[0005] Patent Document 2: WO00 / 78283

[0006] Patent Document 3: Japanese Patent Application Laid-Open No. 2002-348228

[0007] Patent Document 4: Japanese Patent Application Publication No. 2005-225865. Summary of the invention

[0008] An object of the present invention is to provide an external composition containing ascorbic acid having good properties.

[0009] The present invention provides a composition for external use containing ascorbic acid and / or a salt thereof.

[0010] According to the research conducted by the present inventors, it was found that if ascorbic acid and / or its salt is added, coloration may be observed from the time of manufacture or after a certain period of time. In addition, there may be problems of ascorbic acid precipitation during low-temperature storage and problems of transdermal absorbability.

[0011] The present inventors have conducted intensive studies to solve the above problems. As a result, they have found that a composition for external use in which coloring of ascorbic acid is suppressed and transdermal absorbability (skin permeability) of ascorbic acid is excellent can be obtained by containing (A) 10% by mass or less of at least one selected from ascorbic acid and ascorbic acid salts, (B) 30% by mass or more of a diol having three carbon atoms, and (C) 20% by mass or less of water, and further containing ethoxydiglycol in an amount of less than 30% by mass and pH being 4.5 or less; or containing (A) 10 to 25% by mass of at least one selected from ascorbic acid and ascorbic acid salts, (B) 30 to 90% by mass of a diol having three carbon atoms in components excluding (A) and (C), and (C) water, and containing ethoxydiglycol in an amount of less than 30% by mass, (C) / (A) = 0.2 to 5, and pH being 2.0 to 6.0. The present invention has been completed.

[0012] That is, the present invention provides the following external-use composition.

[0013] Item 1.

[0014] A composition for external use, comprising:

[0015] (A) 10% by mass or less of at least one selected from ascorbic acid and its salts;

[0016] (B) 30% by mass or more of a diol having three carbon atoms; and

[0017] (C) 20% by mass or less of water,

[0018] Furthermore, the content of ethoxydiglycol is less than 30% by mass and the pH is 4.5 or less;

[0019] Item 2.

[0020] The composition for external use according to item 1, wherein the content of the component (B) is 40% by mass or more;

[0021] Item 3.

[0022] The external use composition according to item 1 or 2, wherein the content of the ascorbic acid or its salt is 3 to 10% by mass;

[0023] Item 4.

[0024] The composition for external use according to any one of items 1 to 3, wherein the content of (C) water is 10% by mass or less;

[0025] Item 5.

[0026] A composition for external use, comprising:

[0027] (A) 10 to 25% by mass of at least one selected from ascorbic acid and salts of ascorbic acid

[0028] (B) 30 to 90 mass % of the diol having 3 carbon atoms in the components other than (A) and (C); and

[0029] (C) Water,

[0030] Furthermore, the content of ethoxydiglycol is less than 30% by mass, (C) / (A)=0.2 to 5, and the pH is 2.0 to 6.0;

[0031] Item 6.

[0032] The composition for external use according to any one of items 1 to 5, further comprising butylene glycol and / or a lower alcohol;

[0033] Item 7.

[0034] The composition for external use according to any one of items 1 to 6, wherein the component (B) is 1,3-propylene glycol and / or propylene glycol;

[0035] Item 8.

[0036] The composition for external use according to any one of items 1 to 7, wherein the component (B) contains at least 1,3-propylene glycol;

[0037] Item 9.

[0038] The composition for external use according to any one of items 1 to 8, wherein the content of ethoxydiglycol is 10% by mass or less;

[0039] Item 10.

[0040] 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 of 85 to 100% at a wavelength of 700 nm;

[0041] Item 11.

[0042] The composition for external use according to any one of items 1 to 10, wherein the composition for external use is used for promoting the percutaneous absorption of ascorbic acid;

[0043] Item 12.

[0044] A method for preventing coloration and / or crystal precipitation of an external composition containing (A) at least one selected from ascorbic acid and its salts, wherein (A) 10% by mass or less of at least one selected from ascorbic acid and its salts; (B) 30% by mass or more of a diol having three carbon atoms; and (C) 20% by mass or less of water are used together, the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less, thereby preventing coloration and / or crystal precipitation of the external composition.

[0045] Item 13.

[0046] A method for preventing coloration and / or crystal precipitation of an external composition containing (A) at least one selected from ascorbic acid and its salts, comprising: (A) 10 to 25% by mass of at least one selected from ascorbic acid and its salts; (B) 30 to 90% by mass of a diol having three carbon atoms in components other than (A) and (C); and (C) water, wherein the content of ethoxydiglycol is less than 30% by mass, (C) / (A)=0.2 to 5, and the pH is 2.0 to 6.0, thereby preventing coloration and / or crystal precipitation of the external composition.

[0047] According to the present invention, a composition for external use having excellent stability can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] Figure 1 It is a graph showing the results of the percutaneous absorbability test of the external use compositions of Examples and Comparative Examples. DETAILED DESCRIPTION

[0049] In this specification, the unit "mass %" of content has the same meaning as "g / 100g".

[0050] The first aspect of the present invention is firstly a case where at least one selected from ascorbic acid and a salt of ascorbic acid is contained in an amount of 10 mass % or less (hereinafter also referred to as the first invention).

[0051] The composition for external use of the first invention is a composition for external use containing the following components, namely,

[0052] (A) 10% by mass or less of at least one selected from ascorbic acid and a salt of ascorbic acid;

[0053] (B) 30% by mass or more of a diol having three carbon atoms; and

[0054] (C) 20% by mass or less of water,

[0055] Furthermore, the content of ethoxydiglycol (diethylene glycol monoethyl ether) is less than 30% by mass, and the pH is 4.5 or less.

[0056] The external composition of the first invention is stable in a relatively low concentration region of (A) at least one selected from ascorbic acid and a salt of ascorbic acid, and has excellent transdermal absorbability.

[0057] [(A) at least one selected from ascorbic acid and a salt of ascorbic acid]

[0058] In the present invention, ascorbic acid commercially available as a component of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used, and these are generally L-forms.

[0059] Salts of ascorbic acid can also be used. Here, salts of ascorbic acid refer to pharmaceutically acceptable salts. Although not limited, examples include salts formed with organic bases (e.g., salts of trimethylamine salts, triethylamine salts, monoethanolamine salts, triethanolamine salts, pyridinium salts, etc. with tertiary amines, basic ammonium salts such as arginine, etc.), and salts formed 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 ascorbic acid-2-sulfate, etc. can be cited.

[0060] In the present invention, ascorbic acid or a salt thereof may be used alone or in combination of two or more.

[0061] In the topical composition of the first invention, the total content of the component (A) relative to the total amount of the topical composition is appropriately set according to the balance with other components. Relative to the total amount of the topical composition, the total content of the component (A) is 10% by mass or less, then it is not particularly limited, preferably 1% by mass or more, more preferably 2% by mass or more, and further preferably 3% by mass or more. Relative to the total amount of the topical composition, the total content of the component (A) is 10% by mass or less, preferably 9% by mass or less, and further preferably 8% by mass or less. Relative to the total amount of the topical composition, the total content of the component (A) is preferably 1% to 10% by mass, more preferably 2% to 10% by mass, and further preferably 3% to 8% by mass.

[0062] [(B) Diol having three carbon atoms]

[0063] As the diol with three carbon atoms used in the present invention, there is no particular limitation as long as it is used as a component of a skin external preparation in the field of medicines, quasi-drugs or cosmetics. Although the diol with three carbon atoms is not limited, it is preferably 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). For example, either 1,3-propylene glycol or propylene glycol or both thereof can be used as component (B). Such a diol with three carbon atoms can also be used directly as a commercial product. It should be noted that from the viewpoint of relieving irritation to the skin, improving the feeling of use, and inhibiting coloration, it is preferred to combine 1,3-propylene glycol and propylene glycol.

[0064] In the external composition of the first invention, the total content of the component (B) relative to the total amount of the external composition is 30% by mass or more, preferably 35% by mass or more, more preferably 40% by mass or more, and even more preferably 45% by mass or more.

[0065] 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.

[0066] The total content of the component (B) based on the total amount of the external composition of the first invention is preferably 35 to 90% by mass, more preferably 40 to 85% by mass, and even more preferably 45 to 80% by mass.

[0067] In the external composition of the first invention, the ratio of the content of the component (B) to the component (A) is not particularly limited, but is preferably 3 to 300 parts by mass, more preferably 3 to 30 parts by mass, and even more preferably 5 to 25 parts by mass, relative to 1 part by mass of the total content of the component (A).

[0068] [(C) Water]

[0069] The external composition of the first invention is a liquid composition containing water. The ratio of water is not limited, but relative to the external composition, preferably 0.1 mass % or more, more preferably 1 mass % or more, most preferably more than 1 mass %. Although not limited, exceeding 1 mass % can be, for example, 1.01 mass % or more, 1.1 mass % or more. The ratio of water is less than 20 mass % relative to the external composition. Preferably, less than 15 mass %, more preferably less than 10 mass %.

[0070] The total content of the component (C) relative to the total amount of the external composition of the first invention is preferably 1 to 15% by mass, more preferably more than 1 to 10% by mass, and even more preferably 2 to 10% by mass.

[0071] In the external composition of the first invention, the ratio of the content of the component (C) to the component (A) is not particularly limited, but is preferably 0.1 to 10 parts by mass, more preferably 0.125 to 8 parts by mass, and even more preferably 0.2 to 5 parts by mass, relative to 1 part by mass of the total content of the component (A).

[0072] In the present invention, even in a composition containing a small amount of water, the precipitation of ascorbic acid or its salt can be suppressed. In addition, a composition for external use having excellent stability can be prepared. However, from the viewpoint of suppressing the precipitation of ascorbic acid at low temperatures, it is preferred to mix in a small amount.

[0073] [Ethoxydiglycol (diethylene glycol monoethyl ether)]

[0074] In the present invention, ethoxydiglycol is not contained from the viewpoint of mainly improving stability, and even if contained, it is less than 30% by mass. Ethoxydiglycol contained in the external composition at less than 30% by mass is not particularly limited as long as it can be used as a component of a skin external preparation in the field of pharmaceuticals, quasi-drugs or cosmetics.

[0075] In the external composition of the first invention, the content of ethoxydiglycol relative to the total amount of the external composition is less than 30 mass %, preferably 20 mass % or less, more preferably 10 mass % or less, and further preferably 5 mass % or less. The external composition may not contain ethoxydiglycol.

[0076] The total content of ethoxydiglycol is 0 or more and less than 30% by mass, preferably 0 to 20% by mass, more preferably 0 to 10% by mass, and even more preferably about 0 to 5% by mass.

[0077] In the external composition of the first invention, the ratio of the content of the ethoxydiglycol 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 10 parts by mass or 0.01 to 5 parts by mass, depending on circumstances.

[0078] [pH]

[0079] The first external composition of the present invention preferably has an acidic pH of 1.5 to 4.5, more preferably 2 to 4, from the viewpoint of stability of component (A), low irritation to skin and mucous membranes, and good feeling on the skin.

[0080] The external composition of the first invention contains predetermined amounts of the components (A), (B), and (C), and by defining the content of ethoxydiglycol and further adjusting the pH to 4.5 or less, a composition for external use having excellent stability can be obtained.

[0081] [Diethylene glycol ether]

[0082] In the present invention, diglycol ethers other than ethoxydiglycol may be contained or not contained from the viewpoint of mainly improving stability. When contained, it is preferred that the total amount of diglycol ethers together with ethoxydiglycol is less than 40% by mass. Here, diglycol ethers other than ethoxydiglycol are not particularly limited as long as they are used as components of skin external preparations in the fields of pharmaceuticals, quasi-drugs or cosmetics. More than 10 g can be dissolved in 100 g of water. Examples include substances with a degree of polymerization of 2 or less. Specific 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. 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.

[0083] These diethylene glycol ethers may be used alone or in combination of two or more.

[0084] In the external composition of the first invention, the total content of diglycol ethers containing ethoxydiglycol relative to the total amount of the external composition is preferably less than 40% by mass, more preferably 30% by mass or less, further preferably less than 10% by mass, more preferably 10% by mass or less. The external composition may not contain diglycol ether.

[0085] The total content of diglycol ethers including ethoxydiglycol is preferably 0 to less than 40% by mass, more preferably 0 to less than 30% by mass, and even more preferably 0 to about 10% by mass.

[0086] In the external composition of the first invention, the ratio of the content of the diethylene glycol ether component to the component (A) is preferably 0 to 20 parts by mass, more preferably 0 to 10 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.

[0087] The external composition of the first invention contains predetermined amounts of the components (A), (B), and (C), and by defining the total content of diethylene glycol ether and setting the pH to 4.5 or less, a composition with better stability can be obtained.

[0088] [Lower alcohol]

[0089] From the perspective of improving the feeling of use, stability and promotion of percutaneous absorption, as long as the effect of the present invention is not hindered, the external composition of the first invention may contain a lower alcohol in addition to the above-mentioned (A) component, (B) component, and (C) component, and diglycol ethers such as ethoxydiglycol when contained. 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 field of pharmaceuticals, quasi-drugs or cosmetics. In this specification, "lower alcohol" refers to an alcohol of C1-C6. Among them, alcohol of C1-C3 can be particularly preferably used. As such an example, in addition to ethanol, methanol, n-propanol, isopropanol, etc. can also be cited.

[0090] In the external composition of the first invention, the content of the lower alcohol relative to the total amount of the external composition, when contained, is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, further preferably 0.25% by mass or more, further more preferably 1% by mass or more, and most preferably 3% by mass or more. The content of ethanol is preferably 45% by mass or less, more preferably 40% by mass or less, further preferably 35% by mass or less, and further more preferably 20% by mass or less.

[0091] The content of the lower alcohol contained in the external composition of the first invention is preferably 0.01 to 45% by mass, more preferably 0.1 to 40% by mass, further preferably 0.25 to 35% by mass, further more preferably 1 to 20% by mass, and most preferably 3 to 20% by mass.

[0092] [Butanediol]

[0093] From the viewpoint of improving the feeling during use, stability and promotion of percutaneous absorption, the external composition of the present invention may contain butylene glycol (1,3-butylene glycol) in addition to the above-mentioned components (A), (B) and (C) and, if contained, diglycol ethers such as ethoxydiglycol, unless the effects of the present invention are impaired.

[0094] In the external composition of the first invention, the content of butylene glycol relative to the total amount of the external composition, when contained, is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and further preferably 0.25% by mass or more. The content of butylene glycol is preferably 55% by mass or less, more preferably 50% by mass or less, and further preferably 45% by mass or less.

[0095] The content of butylene glycol in the external composition of the first invention is preferably 0.01 to 55% by mass, more preferably 0.1 to 50% by mass, and even more preferably 0.25 to 45% by mass.

[0096] [pH adjuster]

[0097] From the viewpoint of improving the feeling during use, stability, and promotion of percutaneous absorption, the external use composition of the first invention may contain a pH adjuster in addition to the above-mentioned component (A), component (B), and component (C), and, when contained, a diglycol ether such as ethoxydiglycol, unless the effect of the first invention is impaired.

[0098] As the pH adjuster used in the first invention, a compound commonly used as a component of a skin external preparation in the field of pharmaceuticals, quasi-drugs or cosmetics can be used. Although not particularly limited, examples thereof include pH adjusters having an amine (e.g., asparagine or a salt thereof, ε-aminocaproic acid or a salt thereof, glutamic acid or a salt thereof, aminoethylsulfonic acid or a salt thereof, monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, arginine, lysine, L-carnitine, low molecular weight betaine, preferably low molecular weight betaine, more preferably trimethylglycine), an organic acid salt (e.g., sodium lactate, sodium acetate, sodium citrate, sodium succinate, sodium oxalate, calcium gluconate, sodium pyrrolidonecarboxylate, etc.), an inorganic acid salt (e.g., sodium pyrosulfite, potassium pyrosulfite, sodium phosphate, potassium nitrate, sodium borate, preferably sodium pyrosulfite), a basic amino acid and a salt thereof (arginine, lysine, or histidine and a salt thereof), 3-O-ethyl ascorbic acid or a salt thereof, etc.

[0099] In the external composition of the first invention, the total content of the pH adjusting agent relative to the total amount of the external composition is not particularly limited, but is preferably 0.01% by mass or more, and more preferably 0.05% by mass or more. The total content of the pH adjusting agent relative to the total amount of the external composition is preferably 10% by mass or less, and more preferably 5.0% by mass or less. The content of the pH adjusting agent having an amine or amino group is preferably 0.01% by mass to 10% by mass, and more preferably 0.05% by mass to 5.0% by mass, relative to the total amount of the external composition.

[0100] In the external composition of the first invention, the ratio of the content of the pH adjuster 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 0.0005 to 10 parts by mass, further preferably 0.005 to 5 parts by mass, and most preferably 0.01 to 1 part by mass, relative to 1 part by mass of the total content of the component (A).

[0101] [Other ingredients]

[0102] In the topical composition of the present invention, in addition to the above-mentioned (A) component, (B) component, and (C) component, and less than a certain amount of ethoxydiglycol when contained, for the purpose of enhancing or supplementing the various effects of ascorbic acid and for the purpose of adding other useful effects, various components such as whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activation ingredients, firming ingredients, antioxidant ingredients, acne improvement 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 combined and matched. One or more components of whitening ingredients, anti-inflammatory ingredients, antibacterial ingredients, cell activation ingredients, firming ingredients, antioxidant ingredients, anti-aging ingredients or moisturizing ingredients are preferred. Among the combinations of these ingredients, as particularly preferred combinations, combinations with whitening ingredients, combinations of whitening ingredients and antioxidant ingredients, combinations with antioxidant ingredients, combinations with anti-aging ingredients, and combinations of whitening ingredients and anti-aging ingredients can be cited. These components are not particularly limited as long as they have been used in the past or will be used in the future as components of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics, and any substances can be appropriately selected and used.

[0103] The external composition of the present invention can further contain surfactants, solubilizing ingredients, fats and oils, sugars or percutaneous absorption promoting ingredients on the basis of the above-mentioned ingredients. In particular, by containing surfactants, solubilizing ingredients or fats and oils, the stability, effectiveness and feeling of use of ascorbic acid in aqueous solvents can be further improved.

[0104] In the composition for external use of the present invention, various components generally used as components of external preparations in the fields of pharmaceuticals, quasi-drugs or cosmetics may be blended as needed within the range of quantity and quality that do not impair the quality of appearance stability, viscosity, etc. and do not impair the effect of the present invention, such as amino acids, irritation reducing agents, thickeners, preservatives, ultraviolet protection agents, colorants, dispersants, additional pH adjusters, fragrances, etc. These components may be used alone or in combination of two or more.

[0105] The external-use composition of the first invention contains (A) at least one selected from ascorbic acid and ascorbic acid salts 10% or less by mass, (B) a glycol having three carbon atoms 30% or more by mass, (C) water 20% or less by mass, and the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less, and the above-mentioned arbitrary components are mixed as required, and further as required, other solvents or bases of commonly used external preparations can be prepared into various desired forms such as paste, mousse, gel, liquid, emulsion, cream, sheet (substrate support), aerosol, spray, etc. These can be manufactured using methods common in the art.

[0106] The topical composition of the present invention is particularly preferably a transparent or even translucent composition in which ascorbic acid and / or its salts are solubilized. Here, "solubilization" is defined as follows. That is, for example, by ultraviolet-visible absorbance determination, using a spectrophotometer or a photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation) and as the transmittance at a wavelength of 700nm, the transmittance is 80 to 100%, preferably 85 to 100%, and more preferably in the range of 90 to 100%. Here, the transmittance of water is set to 100%. The solubilized composition of the present invention has a transparent or even translucent appearance. The transmittance determination method is more specifically based on the method described in "The 16th Revised Japanese Pharmacopoeia [B] General Test Method 2. Physical Test Method Spectroscopic Determination Method 2.24 Ultraviolet Visible Absorbance Determination Method".

[0107] [Viscosity]

[0108] The topical composition of the present invention can be prepared as a composition having moderate viscosity desired when used, especially for topical compositions applied to the skin. The viscosity of the topical composition of the present invention is not particularly limited. For example, the viscosity 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. The viscosity measurement method is more specifically based on the method described in "16th Revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Other Physical Test Methods 2.53 Viscosity Measurement Method 2.2 Method Rotational Viscometer Method 2.1.3 Cone-Plate Rotational Viscometer (Cone-Plate Viscometer)".

[0109] [use]

[0110] The external composition of the present invention is particularly effective as a whitening agent, anti-inflammatory agent, and anti-aging agent, and has, for example, acne prevention, treatment, and anti-oxidation effects. In addition, by being applied to the skin, it can sometimes improve the transparency of the skin, keep it moist, make the skin texture neat, and suppress roughness. In addition, it can sometimes make pores less noticeable, moisturize the skin, and can also be used for the prevention and treatment of brown spots.

[0111] The external composition of the present invention may be, for example, a basic cosmetic such as a beauty serum, lotion, sunscreen, emulsion, day cream, emulsion, oil, and facial mask; a beauty cosmetic such as a foundation, lipstick, lip balm, mascara, eyeliner, eyeliner pencil, eyebrow powder, and nail polish; a cleaning agent such as a wash paint, a facial cleanser, and a body cleanser; a variety of external compositions belonging to the fields of cosmetics, external medicines, or external quasi-drugs such as an anti-armpit odor agent, an anti-itch agent, a wound treatment agent, a cleaning agent, a detergent, an anti-inflammatory analgesic, an acne treatment agent, a hemorrhoid agent, a disinfectant, a whitening agent, and an ultraviolet protection agent. From the perspective of the effect on the skin, the present invention is preferably used for a product applied to the skin such as a skin external agent (a preparation for the skin).

[0112] [Stabilization method]

[0113] And, the present invention also includes (A) a stabilization method of at least one selected from ascorbic acid and ascorbic acid salts. In the present invention, according to the stabilization method of ascorbic acid, by using (A) at least one selected from ascorbic acid and ascorbic acid salts 10% or less, (B) carbon atoms are three glycols 30% or more, and (C) water 20% or less, and making the content of ethoxydiglycol less than 30% by mass, making pH 4.5 or less, it is possible to form a stable preparation while containing 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 ascorbic acid salts 10% or less, (B) carbon atoms are three glycols 30% or more, and (C) water 20% or less, and making the content of ethoxydiglycol less than 30% by mass, making pH 4.5 or less. Here, stabilization is not limited, but for example, means ensuring stability at high or low temperatures. Specifically, at least when the external composition is stored at 4°C for 1 week, the precipitation of ascorbic acid or a salt thereof is suppressed, or changes in appearance such as coloration are suppressed after storage at 50°C or 40°C for a certain period of time.

[0114] In the method of the present invention, the contents and ratios of (A) at least one selected from ascorbic acid and ascorbic acid salts, (B) a diol having three carbon atoms, and (C) water and ethoxydiglycol are the same as those used in the above-mentioned external composition. In addition, the substance obtained by this method can be used once or several times a day according to the purpose, etc., in a known or customary manner and dosage.

[0115] The second aspect of the present invention is a case where at least one selected from ascorbic acid and a salt of ascorbic acid is present in an amount of 10 to 25% by mass (hereinafter also referred to as the second invention).

[0116] The external-use composition of the second invention contains the following ingredients,

[0117] (A) 10 to 25% by mass of at least one selected from ascorbic acid and salts of ascorbic acid

[0118] (B) 30 to 90% by mass of a diol having three carbon atoms in the components other than (A) and (C); and (C) water,

[0119] The content of ethoxydiglycol is less than 30% by mass, (C) / (A)=0.2 to 5, and the pH is 2.0 to 6.0.

[0120] The external composition of the second invention is stable in a relatively high concentration region of (A) at least one selected from ascorbic acid and a salt of ascorbic acid, and has excellent transdermal absorbability.

[0121] [(A) at least one selected from ascorbic acid and a salt of ascorbic acid]

[0122] In the present invention, ascorbic acid commercially available as a component of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used, and these are generally L-forms.

[0123] Salts of ascorbic acid may also be used. Here, the salts of ascorbic acid are the same as those defined in the case of the first invention. Although not limited, examples thereof include salts formed with organic bases (e.g., salts with tertiary amines such as trimethylamine salts, triethylamine salts, monoethanolamine salts, triethanolamine salts, pyridinium salts, and basic ammonium salts of arginine, etc.), salts formed 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 ascorbic acid-2-sulfate, etc. may be mentioned.

[0124] In the present invention, ascorbic acid or a salt thereof may be used alone or in combination of two or more.

[0125] In the external composition of the second invention, the total content of the component (A) relative to the total amount of the external composition is appropriately set according to the balance with other components. The total content of the component (A) relative to the total amount of the external composition is not particularly limited to 10 to 25% by mass.

[0126] [(B) Diol having three carbon atoms]

[0127] The diol with three carbon atoms used in the external composition of the second invention is not particularly limited as long as it is a substance used as a component of a skin external preparation in the field of medicines, quasi-drugs or cosmetics. It is the same as the substance defined in the case of the first invention. Although the diol with three carbon atoms is not limited, it is preferably 1,3-propylene glycol or propylene glycol. For example, one or both of 1,3-propylene glycol or propylene glycol can be used as component (B). Such a diol with three carbon atoms can also be used directly as a commercial product. It should be noted that from the viewpoint of relieving irritation to the skin, improving the feeling of use, and inhibiting coloring, it is preferred to combine 1,3-propylene glycol and propylene glycol.

[0128] In the external composition of the second invention, the total content of the component (B) is 10% by mass or more, preferably 15% by mass or more, more preferably 20% by mass or more, and even more preferably 25% by mass or more, based on the total amount of the external composition.

[0129] 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, further preferably 80% by mass or less, and further more preferably 70% by mass or less.

[0130] The total content of the component (B) based on the total amount of the external composition is preferably 10 to 90% by mass, more preferably 15 to 85% by mass, further preferably 20 to 80% by mass, and further more preferably 25% to 70% by mass.

[0131] In the external composition of the second invention, the ratio of the content of the component (B) to the component (A) is not particularly limited, but is preferably 0.5 to 10 parts by mass, more preferably 0.75 to 8 parts by mass, and even more preferably 1 to 7 parts by mass, relative to 1 part by mass of the total content of the component (A).

[0132] In the external composition of the second invention, the content of the component (B) relative to the components other than the component (A) and the component (C) described later is preferably 30 to 95% by mass, more preferably 40 to 90% by mass, and even more preferably 50 to 85% by mass.

[0133] [(C) Water]

[0134] The external composition of the second 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 1% to 50% by mass, further more preferably 3% to 40% by mass, and particularly preferably 5% to 30% by mass, relative to the external composition.

[0135] In the external composition of the second invention, the ratio of the content of the component (C) to the component (A) is not particularly limited, but is preferably 0.2 to 5 parts by mass, more preferably 0.5 to 2 parts by mass, and even more preferably 0.6 to 1.8 parts by mass, relative to 1 part by mass of the total content of the component (A).

[0136] [Ethoxydiglycol (diethylene glycol monoethyl ether)]

[0137] In the second invention, mainly from the viewpoint of improving stability, ethoxydiglycol is not contained, or even if contained, it is less than 30% by mass. As ethoxydiglycol contained in the external composition at less than 30% by mass, there is no particular limitation as long as it is used as a component of a skin external preparation in the field of pharmaceuticals, quasi-drugs or cosmetics.

[0138] In the external composition of the second invention, the content of ethoxydiglycol relative to the total amount of the external composition is less than 30 mass %, preferably 20 mass % or less, more preferably 10 mass % or less, and further preferably 5 mass % or less. The external composition may not contain ethoxydiglycol.

[0139] The total content of ethoxydiglycol is 0 or more and less than 30% by mass, preferably 0 to 20% by mass, more preferably 0 to 10% by mass, and even more preferably about 0 to 5% by mass.

[0140] In the external composition of the second invention, the ratio of the content of the ethoxydiglycol 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 10 parts by mass or 0.01 to 5 parts by mass, depending on circumstances.

[0141] [pH]

[0142] The external composition of the present invention may generally have a liquid property of pH 1 to 8, and is preferably pH 2 to 7, more preferably pH 2 to 6, further preferably pH 2 to 5, and particularly preferably in the acidic region of pH 2 to 4.5 from the viewpoint of the stability of ascorbic acid, low irritation to the skin and mucous membranes, and good feeling on the skin during use.

[0143] [Diethylene glycol ether]

[0144] In the present invention, mainly from the viewpoint of improving stability, diglycol ethers other than ethoxydiglycol may be contained or not. When contained, it is preferred that the total amount of diglycol ethers together with ethoxydiglycol is less than 40% by mass. Here, diglycol ethers other than ethoxydiglycol are not particularly limited as long as they are substances used as components of skin external preparations in the fields of pharmaceuticals, quasi-drugs or cosmetics. More than 10 g can be dissolved in 100 g of water. Examples include substances with a degree of polymerization of 2 or less. Specific 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. 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.

[0145] These diethylene glycol ethers may be used alone or in combination of two or more.

[0146] In the external composition of the second invention, the total content of diglycol ethers containing ethoxydiglycol relative to the total amount of the external composition is preferably less than 40% by mass, more preferably 30% by mass or less, further preferably less than 10% by mass, more preferably 10% by mass or less, and the external composition may not contain diglycol ether.

[0147] The total content of diglycol ethers including ethoxydiglycol is preferably 0 to less than 40% by mass, more preferably 0 to less than 30% by mass, and even more preferably 0 to about 10% by mass.

[0148] In the external composition of the second invention, the ratio of the content of the diethylene glycol ether component to the component (A) is preferably 0 to 20 parts by mass, more preferably 0 to 10 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.

[0149] The external composition of the second invention contains predetermined amounts of the components (A), (B), and (C), and a predetermined total content of diethylene glycol ether, and has a pH of 1.5 to 4.5, more preferably 2 to 4.5, thereby being able to provide an external composition with better stability.

[0150] [Lower alcohol]

[0151] From the perspective of improving the feeling of use, stability and promotion of percutaneous absorption, as long as the effect of the present invention is not hindered, the external composition of the second invention may contain a lower alcohol in addition to the above-mentioned (A) component, (B) component, and (C) component, and diglycol ethers such as ethoxydiglycol when contained. The lower alcohol used in the present invention is not particularly limited as long as it is a substance 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 an example, in addition to ethanol, methanol, n-propanol, isopropanol, etc. can be cited.

[0152] In the external-use composition of the second invention, when contained, the content of the lower alcohol relative to the total amount of the external-use composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, further preferably 0.25% by mass or more, further more preferably 1% by mass or more, and most preferably 3% by mass or more. The content of ethanol is preferably 45% by mass or less, more preferably 40% by mass or less, further preferably 35% by mass or less, and further more preferably 20% by mass or less.

[0153] The content of the lower alcohol contained in the external composition of the second invention is preferably 0.01 to 45% by mass, more preferably 0.1 to 40% by mass, further preferably 0.25 to 35% by mass, further more preferably 1 to 20% by mass, and most preferably 3 to 20% by mass.

[0154] [Butanediol]

[0155] From the viewpoint of improving the feeling during use, stability and promotion of percutaneous absorption, the external composition of the present invention may contain butylene glycol (1,3-butylene glycol) in addition to the above-mentioned components (A), (B) and (C) and diglycol ethers such as ethoxydiglycol when contained, unless the effects of the present invention are impaired.

[0156] In the external composition of the second invention, when contained, the content of butylene glycol relative to the total amount of the external composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and further preferably 0.25% by mass or more. The content of butylene glycol is preferably 40% by mass or less, more preferably 35% by mass or less, and further preferably 30% by mass or less.

[0157] The content of butylene glycol in the external composition of the second invention is preferably 0.01 to 40% by mass, more preferably 0.1 to 35% by mass, and even more preferably 0.25 to 30% by mass.

[0158] [pH adjuster]

[0159] From the viewpoint of improving the feeling during use, stability, and promotion of percutaneous absorption, the external use composition of the second invention may contain a pH adjuster in addition to the above-mentioned component (A), component (B), and component (C), and diglycol ethers such as ethoxydiglycol when contained, as long as it does not hinder the effect of the second invention.

[0160] As the pH adjuster used in the second invention, a compound generally used as a component of a skin external preparation in the field of pharmaceuticals, quasi-drugs or cosmetics can be used. Although not particularly limited, examples thereof include pH adjusters having an amine (e.g., asparagine or a salt thereof, ε-aminocaproic acid or a salt thereof, glutamic acid or a salt thereof, aminoethylsulfonic acid or a salt thereof, monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, arginine, lysine, L-carnitine, low molecular weight betaine, preferably low molecular weight betaine, more preferably trimethylglycine), an organic acid salt (e.g., sodium lactate, sodium acetate, sodium citrate, sodium succinate, sodium oxalate, calcium gluconate, sodium pyrrolidonecarboxylate, etc.), an inorganic acid salt (e.g., sodium pyrosulfite, potassium pyrosulfite, sodium phosphate, potassium nitrate, sodium borate, preferably sodium pyrosulfite), a basic amino acid and a salt thereof (arginine, lysine, or histidine and a salt thereof), 3-O-ethyl ascorbic acid or a salt thereof, etc.

[0161] In the external composition of the second invention, the total content of the pH adjusting agent relative to the total amount of the external composition is not particularly limited, but is preferably 0.01% by mass or more, and more preferably 0.05% by mass or more. The total content of the pH adjusting agent relative to the total amount of the external composition is preferably 20% by mass or less, and more preferably 10% by mass or less. The content of the pH adjusting agent having an amine or amino group is preferably 0.01% by mass to 20% by mass, and more preferably 0.05% by mass to 10% by mass, relative to the total amount of the external composition.

[0162] In the external composition of the second invention, the ratio of the content of the pH adjuster 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 0.0005 to 10 parts by mass, further preferably 0.005 to 5 parts by mass, and most preferably 0.01 to 1 part by mass, relative to 1 part by mass of the total content of the component (A).

[0163] [Other ingredients]

[0164] In the external composition of the second invention, in addition to the above-mentioned (A) component, (B) component, and (C) component, and less than a certain amount of ethoxydiglycol when contained, for the purpose of enhancing or supplementing the various effects of ascorbic acid and for the purpose of adding other useful effects, various components such as whitening components, anti-inflammatory components, antibacterial components, cell activation components, firming components, antioxidant components, acne improvement components, anti-aging components, collagen and other biological component synthesis promoting components, blood circulation promoting components, moisturizing components, anti-aging components, etc. can be combined and matched. One or more components of whitening components, anti-inflammatory components, antibacterial components, cell activation components, firming components, antioxidant components, anti-aging components or moisturizing components are preferred. Among the combinations of these components, as particularly preferred combinations, 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 can be cited. There are no particular limitations on these components as long as they have been used in the past or can be used in the future as components of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics, and any substances can be appropriately selected and used.

[0165] The external composition of the present invention can further contain surfactants, solubilizing ingredients, fats and oils, sugars or percutaneous absorption promoting ingredients on the basis of the above-mentioned ingredients. In particular, by containing surfactants, solubilizing ingredients or fats and oils, the stability, effectiveness and feeling of use of ascorbic acid in aqueous solvents can be further improved.

[0166] In the external composition of the present invention, various components generally used as components of 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., can be added as needed without impairing the quality of the appearance stability, viscosity, etc., and within the range of quantity and quality that do not impair the effect of the present invention. It should be noted that these components can be added alone or in any combination of two or more.

[0167] The external composition of the second invention can be prepared by containing (A) at least one selected from ascorbic acid and ascorbic acid salts in an amount of 10 to 25% by mass; (B) 30 to 90% by mass of a diol having three carbon atoms in the components other than (A) and (C); and (C) water, and the content of ethoxydiglycol is less than 30% by mass, (C) / (A)=0.2 to 5, and pH of 2.0 to 6.0, and the above-mentioned arbitrary components are mixed as required, and other solvents, bases of commonly used external preparations, etc. are further mixed as required, thereby being prepared into various desired forms such as paste, mousse, gel, liquid, emulsion, cream, sheet (substrate-carried), aerosol, and spray. These can be manufactured using the usual methods in the art.

[0168] The topical composition of the present invention is particularly preferably a transparent or even translucent composition in which ascorbic acid and / or its salts are solubilized. Here, "solubilization" is defined as follows. That is, for example, by ultraviolet-visible absorbance determination, using a spectrophotometer or a photoelectric photometer UV-2450 (manufactured by Shimadzu Corporation), as the transmittance at a wavelength of 700nm, the transmittance is 80 to 100%, preferably 85 to 100%, and more preferably in the range of 90 to 100%. Here, the transmittance of water is set to 100%. The solubilized composition of the present invention has a transparent or even translucent appearance. The transmittance determination method is more specifically based on the method described in "The 16th Revised Japanese Pharmacopoeia [B] General Test Method 2. Physical Test Method Spectroscopic Determination Method 2.24 Ultraviolet Visible Absorbance Determination Method".

[0169] [Viscosity]

[0170] The topical composition of the present invention can be prepared as a composition having a desired moderate viscosity when used as a topical composition, especially for skin application. The viscosity of the topical composition of the present invention is not particularly limited. For example, the viscosity 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. The viscosity measurement method is more specifically based on the method described in "16th Revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Other Physical Test Methods 2.53 Viscosity Measurement Method 2.2 Method Rotational Viscometer Method 2.1.3 Cone-Plate Rotational Viscometer (Cone-Plate Viscometer)".

[0171] [use]

[0172] The external composition of the present invention is particularly effective as a whitening agent, anti-inflammatory agent, and anti-aging agent, and has, for example, acne prevention, treatment, and anti-oxidation effects. In addition, by applying to the skin, it sometimes has the effects of improving the transparency of the skin, keeping it moist, tidying the skin texture, and suppressing roughness. In addition, it sometimes has the effects of making pores less noticeable and moisturizing the skin. In addition, it can also be used for the prevention and treatment of brown spots.

[0173] The external composition of the present invention may be, for example, a basic cosmetic such as a beauty serum, lotion, sunscreen, emulsion, day cream, emulsion, oil, and facial mask; a cosmetic such as a foundation, lipstick, lip balm, mascara, eyeliner, eyeliner pencil, eyebrow powder, and nail polish; a cleaning agent such as a wash paint, a facial cleanser, and a body cleanser; a variety of external compositions belonging to the fields of cosmetics, external medicines, or external quasi-drugs, such as an anti-armpit odor agent, an antipruritic agent, a wound treatment agent, a cleaning agent, a cleaning agent, an anti-inflammatory analgesic agent, an acne treatment agent, a hemorrhoid agent, a bactericidal disinfectant, a whitening agent, and an ultraviolet protection agent. In view of the effect on the skin, the present invention is preferably used in a product for the skin such as an external skin agent (a preparation for the skin).

[0174] [Stabilization method]

[0175] Furthermore, the present invention also includes a stabilization method of (A) at least one selected from ascorbic acid and a salt of ascorbic acid. In the present invention, according to the stabilization method of ascorbic acid, by containing (A) 10 to 25% by mass of at least one selected from ascorbic acid and a salt of ascorbic acid, (B) 30 to 90% by mass of a diol having three carbon atoms in the components other than (A) and (C), and (C) water, the content of ethoxydiglycol is less than 30% by mass, (C) / (A)=0.2 to 5, and the pH is 2.0 to 6.0, it is possible to form a formulation containing ascorbic acid and being stable at the same time. 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 containing (A) 10 to 25% by mass of at least one selected from ascorbic acid and a salt of ascorbic acid; (B) 30 to 90% by mass of a diol having three carbon atoms in the components other than (A) and (C); and (C) water, and the content of ethoxydiglycol is less than 30% by mass, (C) / (A)=0.2 to 5, and pH is 2.0 to 6.0. Here, although not limited, stabilization means, for example, ensuring stability at high or low temperatures. Specifically, it means suppressing the precipitation of ascorbic acid or a salt thereof when the external composition is stored at 4°C for 1 week, or suppressing changes in appearance such as coloring after storage at 50°C or 40°C for a certain period of time.

[0176] In the method of the present invention, the contents and ratios of (A) at least one selected from ascorbic acid and ascorbic acid salts, (B) a diol having three carbon atoms, and (C) water and ethoxydiglycol are the same as those used in the external composition. In addition, the substance obtained by the present method can be used once or several times a day according to the intended use, in a known or customary manner and dosage.

[0177] Example

[0178] Next, the present invention will be specifically described using 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 %.

[0179] Compositions for external use having the compositions shown in Tables 1 to 6 were prepared according to conventional methods. Thereafter, these compositions were subjected to tests according to each test item.

[0180] [Ascorbic acid coloration inhibition confirmation test]

[0181] The presence or absence of coloration inhibition of the external-use compositions of several embodiments and comparative examples of the present invention after storage at 40°C or 50°C was evaluated visually or using a colorimeter. Specifically, according to the prescriptions (mass %) recorded in various prescription tables, ascorbic acid was added to the mixed solution of various components, heated and mixed at 60°C for 10 minutes and dissolved to prepare the composition. The prepared composition was filled into a transparent glass bottle and allowed to stand in a constant temperature and humidity machine at 40°C or 50°C for 1 week (expressed as 1W) or 4 weeks (expressed as 4W). During each measurement period, the container was taken out of the constant temperature machine and evaluated after being constant temperature at 25°C. The presence and degree of coloration were determined by measuring each test solution based on visual inspection or using a colorimeter.

[0182] The measurement by the colorimeter was performed by placing 1 mL of the test solution in a glass cell (CM-A97, thickness 2 mm), and the color difference was measured using a spectrophotometer CM-5 (manufactured by Konica Minolta, Inc.) to measure the b value. The measured value was Δb* when purified water was used as a blank. The change in color difference was calculated according to the following calculation formula.

[0183] (Amount of change in color difference (Δb value)) = (Measurement value of the test solution after heat preservation (b value after accelerated test)) - (Measurement value of the test solution before heat preservation (b value before accelerated test))

[0184] The b value is used as an index to indicate transparency. Therefore, the smaller the Δb value, the less coloring. In addition, when the ratio of Δb between the two is 1.4 or less, the difference in coloring is not felt strongly. On the other hand, when it exceeds 1.4, the difference in coloring can be clearly observed, resulting in poor quality. Therefore, the presence or absence of coloring is judged by whether the ratio is 1.4 or less when the Δb value of the sample where no change in coloring is observed is set to 1.

[0185] [Ascorbic acid precipitation inhibition confirmation test]

[0186] The external-use compositions of several embodiments of the present invention and comparative examples were visually evaluated for the presence or absence of ascorbic acid precipitation when the preparations were stored at low temperatures. Specifically, according to the prescriptions (mass %) recorded in various prescription tables, ascorbic acid was added to the mixed solution of various components, heated and mixed at 60°C for 10 minutes to dissolve, and the composition was prepared. The prepared composition was filled in a transparent glass bottle, left to stand at 4°C under light-shielding conditions, and stored for 1 week or 4 weeks, and each test solution was visually observed to determine whether crystal precipitation occurred.

[0187] <Evaluation Criteria>

[0188] ○: The state of the precipitate cannot be visually confirmed; ×: The state of the precipitate can be visually confirmed.

[0189] [Ascorbic acid percutaneous absorption test]

[0190] The percutaneous absorbability of the external-use compositions of several embodiments and comparative examples of the present invention was verified. By improving the percutaneous absorbability, ascorbic acid can penetrate into the inner part of the muscle, thereby expecting a higher anti-aging effect as a composition. That is, depending on the situation, the effect of ascorbic acid can be affected deep in the stratum corneum.

[0191] The percutaneous absorbability of ascorbic acid in the external use compositions prepared in Examples and Comparative Examples was confirmed by evaluation measurement based on the horny layer.

[0192] Specifically, first, the amount of ascorbic acid in the stratum corneum of the skin components of the upper arm and forearm of a healthy person was confirmed by tape stripping. Two healthy male subjects who agreed to participate in the experiment based on their own will were used as subjects. A gauze soaked with 750uL of the external composition of an embodiment or a comparative example was attached to the inner part of the upper arm of the subject at 1.5cm×1.5cm and allowed to stand for 5 minutes. After removing the gauze, a new gauze was used to remove the sample remaining on the skin surface and allowed to stand for 30 minutes. This time was used as the penetration time of the sample. Thereafter, an invisible tape (manufactured by Sumitomo 3M) was used to perform 7 consecutive tape strippings from the applied part to strip keratinocytes, and all layers of the obtained tape were used as specimens for measurement. Through preliminary experiments, it was confirmed that the necessary amount of keratinocytes could be stripped each time the tape was stripped and no inflammation or pain was produced after the tape was stripped, thereby setting the number of tape strippings.

[0193] The obtained specimen for measurement was extracted with 1 mL of an extraction solvent of a mixture of Tritonx-100 (manufactured by MP Biomedicals), mercaptoethanol (manufactured by Wako Pure Chemical Industries, Ltd.) and purified water (1:1:1000). The amount of ascorbic acid permeation (μg / mL) was measured by HPLC using the extraction solution from which foreign matter was removed by passing through a 0.45μm syringe filter (manufactured by GL Science). The amount of L-ascorbic acid contained in the solution was measured using an Agilent HPLC (mobile phase: acetonitrile / 0.02M phosphoric acid solution (pH 3.0) (1:9), absorbance detection wavelength: 270nm) equipped with a reverse phase column (CAPCELL PAK C18 SG120, manufactured by Shiseido) . The value obtained by averaging the measured values ​​of the specimens for measurement collected from three locations on the arms of two subjects was taken as the permeation amount (μg / cm 2 ) are compared as the result.

[0194] In addition, the detection of ascorbic acid by HPLC was performed using an ultraviolet absorption photometer at a wavelength of 270 nm using a reverse phase column (CAPCELL PAK C18 SG120, manufactured by Shiseido Co., Ltd.), and the content was calculated based on the standard curve.

[0195] (Examples 1-1 to 1-6, Comparative Examples 1-1 to 1-3)

[0196] The compositions for external use of the examples and comparative examples having the compositions shown in Table 1 were prepared by a conventional method. Among the evaluation items, the Δb ratio was the ratio of the comparative values, with the color difference value of the composition for external use in Example 1-1 as the reference (1). That is, the stability ratio represents the Δb ratio.

[0197] The results of the ascorbic acid coloration inhibition confirmation test of the compositions of Examples and Comparative Examples are shown in Tables 1 and 2 in combination.

[0198] Table 1

[0199]

[0200] [Table 2]

[0201]

[0202] The compositions of the examples had a coloration-suppressing effect even when stored at high temperatures and showed excellent stability over a long period of time. On the other hand, the compositions of the comparative examples showed coloration under the storage conditions of the test.

[0203] (Examples 2-1 to 2-2, Comparative Example 2-1)

[0204] The compositions for external use of the examples and comparative examples having the compositions shown in Table 3 were prepared according to conventional methods. The Δb ratio in the evaluation item is the ratio of the values ​​for comparison, with the color difference value of the composition for external use of Example 2-1 being taken as the reference (1). That is, the stability ratio indicates the ratio when the Δb value of Example 2-1 is taken as 1.

[0205] Table 3 shows the results of the ascorbic acid coloration inhibition confirmation test and the results of the ascorbic acid precipitation inhibition confirmation test of the compositions of Examples and Comparative Examples.

[0206] [Table 3]

[0207]

[0208] That is, it was found that the compositions shown in Examples achieved both the properties of suppressing the precipitation of ascorbic acid and suppressing the coloring of the composition.

[0209] (Examples 3-1 to 3-3, Comparative Examples 3-1 to 3-2)

[0210] The external-use compositions of Examples and Comparative Examples having the compositions shown in Table 4 were prepared according to conventional methods.

[0211] Table 4 shows the results of the ascorbic acid coloration inhibition confirmation test and the ascorbic acid precipitation inhibition confirmation test of the compositions of Examples and Comparative Examples.

[0212] [Table 4]

[0213]

[0214] (Examples 4-1 to 4-3, Comparative Examples 4-1 to 4-2)

[0215] The external-use compositions of Examples and Comparative Examples having the compositions shown in Table 5 were prepared according to conventional methods.

[0216] The results of the ascorbic acid coloration inhibition confirmation test and the results of the ascorbic acid precipitation inhibition confirmation test of the compositions of the examples and comparative examples are shown in Table 4. Among the evaluation items, the Δb ratio is the ratio of the comparative value with the color difference value of the external composition of Example 4-1 as the reference (1). That is, the stability ratio indicates the ratio when the Δb value of Example 4-1 is set to 1.

[0217] [Table 5]

[0218]

[0219] It can be seen that the composition shown in the examples achieves both the properties of suppressing the precipitation of ascorbic acid at low temperatures and suppressing the coloring of the composition. For example, when the ethoxydiglycol is at a high concentration of 40% by mass or more, precipitation can be seen especially at low temperatures due to the low pH. For a formulation with a small increase in pH, precipitation of ethoxydiglycol at low temperatures is not seen even at a high concentration, but at 30% by mass or more, a high degree of coloring is clearly seen. Therefore, even if ethoxydiglycol is incorporated, it is preferably less than 30% by mass.

[0220] Furthermore, the results of the ascorbic acid coloration inhibition confirmation test, ascorbic acid precipitation inhibition confirmation test, and percutaneous absorbability test of the compositions of other examples and comparative examples are shown in Table 6. Among the evaluation items, the Δb ratio is the ratio of the comparative value with the color difference value of the external composition of Example 5-1 as the reference (1). That is, the stability ratio indicates the ratio when the Δb value of Example 5-1 is set to 1.

[0221] [Table 6]

[0222]

[0223] Comparison of the compositions of the Examples with the compositions of the Comparative Examples shows that the precipitation of ascorbic acid can be suppressed even under low temperature storage, and that the coloration of the compositions during storage can be suppressed. In addition, it is found that the compositions of the present invention also have excellent transdermal absorbability.

[0224] The results of the transdermal absorbability of the compositions of Examples 5-1 to 5-2 and Comparative Examples 5-1 to 5-2 are shown in Figure 1 .

[0225] Next, compositions for external use having the compositions shown in Tables 7 to 9 were prepared according to conventional methods. Thereafter, these compositions were subjected to tests based on the respective test items.

[0226] [Ascorbic acid coloration inhibition confirmation test]

[0227] The external compositions of the compositions shown in Tables 7 to 9 were evaluated visually and with a colorimeter for suppression of coloration after storage at 40° C. or 50° C. Specifically, a confirmation test was performed in exactly the same manner as in Examples 1 to 5 and Comparative Examples 1 to 5.

[0228] [Ascorbic acid precipitation inhibition confirmation test]

[0229] The presence or absence of ascorbic acid precipitation was visually evaluated when the external use compositions of the compositions shown in Tables 7 to 9 were stored at low temperatures. Specifically, the confirmation test was performed in exactly the same manner as in Examples 1 to 5 and Comparative Examples 1 to 5.

[0230] [Ascorbic acid percutaneous absorption test]

[0231] The percutaneous absorbability of the external-use compositions of several embodiments and comparative examples of the second invention was verified. By improving the percutaneous absorbability, ascorbic acid penetrates into the inner part of the muscle, and thus a higher anti-aging effect as a composition is expected. That is, depending on the situation, the effect of ascorbic acid can be brought to the deep part of the stratum corneum.

[0232] The percutaneous absorbability of ascorbic acid in the external compositions prepared in Examples and Comparative Examples was confirmed by evaluation based on the horny layer. Specifically, the confirmation test was performed by the same method as that performed in Examples 1 to 5 and Comparative Examples 1 to 5.

[0233] (Examples 6-1 to 8-1, Comparative Examples 6-2 to 8-3)

[0234] According to the conventional method, the external composition of the examples and comparative examples of the composition shown in Table 7 was prepared. In the evaluation items in the same table, the ratio of Δb is the ratio of the comparative value, with the color difference value of the external composition in Example 1 as the reference (1). That is, the stability ratio represents the ratio of Δb. In addition, the ratio recorded in the column of the transdermal absorption test results of the external composition of the examples and comparative examples is a value obtained by taking the transdermal absorption amount of Comparative Example 5-1 (Formulation 40) in which 1,3-butanediol is compounded in the base as 1, and the ratio is calculated.

[0235] Ratio = (percutaneous absorption amount (μg / cm2) of any composition in the examples and comparative examples 2 ) / (Percutaneous absorption amount of the composition of Comparative Example 5-1 (μg / cm 2 )

[0236] The results of each test of the compositions of Examples and Comparative Examples are collectively shown in Tables 7 to 9.

[0237] [Table 7]

[0238]

[0239] [Table 8]

[0240]

[0241] [Table 9]

[0242]

[0243] The composition of the embodiment has a coloration suppression effect even when stored at high temperature, showing excellent stability for a long time. On the other hand, the composition of the comparative example is colored under the storage conditions of the test. In addition, the composition of the embodiment suppresses precipitation at low temperatures compared to the composition of the comparative example.

[0244] [Prescription Example]

[0245] The following Tables 10 to 12 show the formulation examples. All the formulation examples can be preferably used in lotions, beauty serums, etc. The contents in the formulation examples are all in mass %.

[0246]

[0247]

[0248]

Claims

1. A composition for external use, comprising: (A) at least one selected from ascorbic acid and salts of ascorbic acid, the total amount of which is 1% by mass or more and 10% by mass or less, (B) 30% by mass or more of a diol having three carbon atoms, (C) water, 5 mass % to 10 mass %, and 1,3-Butanediol; Furthermore, the content of ethoxydiglycol is less than 30% by mass, the content of ethanol is less than 20% by mass, and the pH is 4.5 or less.

2. The composition for external use according to claim 1, wherein The content of the component (B) is 40% by mass or more.

3. The external use composition according to claim 1 or 2, wherein The total content of the ascorbic acid and its salt is 3 to 10% by mass.

4. The external use composition according to claim 1 or 2, wherein The concentration of the 1,3-butanediol is 2% by mass to 55% by mass.

5. The external use composition according to claim 1 or 2, wherein The component (B) is 1,3-propanediol and / or propylene glycol.

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

7. The external use composition according to claim 1 or 2, wherein The content of ethoxydiglycol is 10% by mass or less.

8. The external-use composition according to claim 1 or 2, wherein The external composition is a solubilized external composition having a transmittance of 85 to 100% at a wavelength of 700 nm.

9. The composition for external use according to claim 1 or 2, wherein The external composition is used for promoting the percutaneous absorption of ascorbic acid.

10. A method for preventing coloration and / or crystal precipitation of an external composition containing (A) at least one selected from ascorbic acid and a salt of ascorbic acid, wherein: By combining: (A) at least one selected from ascorbic acid and salts of ascorbic acid, the total amount of which is 1% by mass or more and 10% by mass or less, (B) 30% by mass or more of a diol having three carbon atoms, (C) water, 5 mass % to 10 mass %, and 1,3-Butanediol; Furthermore, the content of ethoxydiglycol is less than 30% by mass, and the content of ethanol is less than 20% by mass. And make the pH below 4.5, Thus, coloration of the external composition and / or precipitation of crystals can be prevented.

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