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

Abstract

Provided is a composition for external use having excellent stability and feeling of use. A composition for external use, which contains (A) 10% by mass or less of at least one substance selected from ascorbic acid and a salt of ascorbic acid, (B) 30% by mass or more of a diol having three carbon atoms, and (C) 20% by mass or less of water. The content of ethoxydiethylene glycol is less than 30% by mass, and the pH is 4.5 or less. Alternatively, the composition for external use contains (A) 10-25% by weight of at least one substance selected from ascorbic acid and a salt of ascorbic acid, (B) 30-90% by mass of a diol having three carbon atoms in the components other than (A) and (C), and (C) water, the content of ethoxydiethylene glycol being less than 30% by mass, (C) / (A) = 0.2-5, and the pH being 2.0-6.0.

Description

[0001] This application is a divisional application of Patent Application No. 201980024383.7 (International filing date: March 29, 2019; Invention title: Topical composition containing ascorbic acid and / or its salt). Technical Field

[0002] The present invention relates to a topical composition containing ascorbic acid and / or its salt. Background Art

[0003] It is known that ascorbic acid exhibits various effects such as anti-inflammatory effect, acne improvement effect, whitening effect, anti-aging effect, antioxidant effect, effect of activating cells by promoting the synthesis of biological components such as collagen, and effect of inhibiting cell damage and DNA damage caused by ultraviolet rays in epidermal keratinocytes. Due to these expected effects, it is widely used as a topical skin agent.

[0004] In order to stably solubilize ascorbic acid in an aqueous topical skin agent, some methods 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).

[0005] Patent Document 1: WO02 / 19972

[0006] Patent Document 2: WO00 / 78283

[0007] Patent Document 3: Japanese Patent Application Laid-Open No. 2002-348228

[0008] Patent Document 4: Japanese Patent Application Laid-Open No. 2005-225865. Summary of the Invention

[0009] An object of the present invention is to provide a topical composition containing ascorbic acid having good properties.

[0010] The present invention provides a topical composition containing ascorbic acid and / or its salt.

[0011] According to the research of the present inventors, it has been found that when ascorbic acid and / or its salt is formulated, coloring may be observed from the time of manufacture, or coloring may be observed after a certain period of time. In addition, there are sometimes problems such as precipitation of ascorbic acid during low-temperature storage and percutaneous absorption.

[0012] In order to solve this problem, the present inventors conducted repeated and in-depth research, and as a result, it was found that: by containing (A) at least one selected from ascorbic acid and salts of ascorbic acid in an amount of 10% by mass or less, (B) a diol having three carbon atoms in an amount of 30% by mass or more, (C) water in an amount of 20% by mass or less, further making the content of ethoxydiglycol less than 30% by mass, and making the pH 4.5 or less, or by containing (A) at least one selected from ascorbic acid and salts of ascorbic acid in an amount of 10 to 25% by mass, (B) a diol having three carbon atoms in an amount of 30 to 90% by mass in the components excluding (A) and (C), and (C) water, and making the content of ethoxydiglycol less than 30% by mass, (C) / (A)=0.2 to 5, and making the pH 2.0 to 6.0, an external composition capable of suppressing the coloring of ascorbic acid and having excellent percutaneous absorbability (skin permeability) of ascorbic acid can be obtained, and thus the present invention was completed.

[0013] That is, the present invention provides an external composition described below.

[0014] Item 1.

[0015] An external composition containing:

[0016] (A) at least one selected from ascorbic acid and salts of ascorbic acid in an amount of 10% by mass or less;

[0017] (B) a diol having three carbon atoms in an amount of 30% by mass or more; and

[0018] (C) water in an amount of 20% by mass or less,

[0019] and the content of ethoxydiglycol is less than 30% by mass, and the pH is 4.5 or less;

[0020] Item 2.

[0021] The external composition according to Item 1, wherein the content of the component (B) is 40% by mass or more;

[0022] Item 3.

[0023] The external composition according to Item 1 or 2, wherein the content of ascorbic acid or its salt is 3 to 10% by mass;

[0024] Item 4.

[0025] The external composition according to any one of Items 1 to 3, wherein the content of (C) water is 10% by mass or less;

[0026] Item 5.

[0027] An external composition containing:

[0028] (A) At least 10 to 25% by mass of at least one selected from ascorbic acid and salts of ascorbic acid

[0029] (B) Diol having three carbon atoms is 30 to 90% by mass in components other than (A) and (C); and

[0030] (C) Water,

[0031] 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;

[0032] Item 6.

[0033] The external composition according to any one of Items 1 to 5, further comprising butanediol and / or lower alcohol;

[0034] Item 7.

[0035] The external composition according to any one of Items 1 to 6, wherein the component (B) is 1,3-propanediol and / or propylene glycol;

[0036] Item 8.

[0037] The external composition according to any one of Items 1 to 7, wherein the component (B) contains at least 1,3-propanediol;

[0038] Item 9.

[0039] The external composition according to any one of Items 1 to 8, wherein the content of ethoxydiglycol is 10% by mass or less;

[0040] Item 10.

[0041] The external composition according to any one of Items 1 to 9, wherein the external composition is a solubilizing external composition having a transmittance of 85 to 100% at a wavelength of 700 nm;

[0042] Item 11.

[0043] The external composition according to any one of Items 1 to 10, wherein the external composition is for promoting percutaneous absorption of ascorbic acid;

[0044] Item 12.

[0045] A method for preventing coloring and / or precipitation of crystals in an external composition containing at least one selected from (A) ascorbic acid and salts of ascorbic acid, wherein at least one selected from (A) ascorbic acid and salts of ascorbic acid is 10% by mass or less; (B) a diol having three carbon atoms is 30% by mass or more; and (C) water is 20% by mass or less, and the content of ethoxydiglycol is less than 30% and the pH is 4.5 or less, thereby preventing coloring and / or precipitation of crystals in the external composition.

[0046] Item 13.

[0047] A method for preventing coloring and / or precipitation of crystals in an external composition containing at least one selected from (A) ascorbic acid and salts of ascorbic acid, containing at least one selected from (A) ascorbic acid and salts of ascorbic acid in an amount of 10 to 25% by mass, (B) a diol having three carbon atoms in an amount of 30 to 90% by mass among the components other than (A) and (C); and (C) water, and the content of ethoxydiglycol is less than 30%, (C) / (A)=0.2 to 5, and the pH is 2.0 to 6.0, thereby preventing coloring and / or precipitation of crystals in the external composition.

[0048] According to the present invention, an external composition having excellent stability can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 It is a coordinate diagram showing the results of percutaneous absorption tests of the external compositions of the examples and comparative examples. DETAILED DESCRIPTION

[0050] In this specification, the unit "mass%" of the content has the same meaning as "g / 100g".

[0051] In the first aspect of the present invention, first, it is the case where at least one selected from ascorbic acid and salts of ascorbic acid is 10% by mass or less (hereinafter also referred to as the first invention).

[0052] The external composition of the first invention is an external composition containing the following components, namely,

[0053] (A) At least one selected from ascorbic acid and salts of ascorbic acid is 10% by mass or less;

[0054] (B) A diol having three carbon atoms is 30% by mass or more; and

[0055] (C) Water is 20% by mass or less,

[0056] and the content of ethoxydiglycol (diethylene glycol monoethyl ether) is less than 30% and the pH is 4.5 or less.

[0057] The external composition of the first invention is very stable in a relatively low concentration range of at least one selected from (A) ascorbic acid and salts of ascorbic acid, and has excellent percutaneous absorbability.

[0058] [(A) at least one selected from ascorbic acid and salts of ascorbic acid]

[0059] In the present invention, ascorbic acid commercially available as a component of a topical skin agent in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used, and these are usually the L-form.

[0060] Salts of ascorbic acid can also be used. Here, the salts of ascorbic acid refer to pharmaceutically acceptable salts. Although not limited, for example, salts formed with organic bases (such as salts with tertiary amines like trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, pyridine salt, etc., basic ammonium salts such as arginine salt, etc.), salts formed with inorganic bases (such as ammonium salt, sodium salt, potassium salt and other alkali metal salts, calcium salt, magnesium salt and other alkaline earth metal salts, aluminum salt, etc.) can be mentioned. Particularly preferred salts of ascorbic acid are sodium salt and potassium salt. Specifically, sodium ascorbate, sodium ascorbate monophosphate, sodium ascorbate diphosphate, sodium ascorbate triphosphate, sodium ascorbate - 2 - sulfate, etc. can be mentioned.

[0061] In the present invention, ascorbic acid or its salts can be used singly or in combination of two or more.

[0062] In the external composition of the first invention, the total content of component (A) relative to the total amount of the external composition is appropriately set according to the balance with other components. When the total content of component (A) is 10% by mass or less relative to the total amount of the external composition, there is no particular limitation, preferably 1% by mass or more, more preferably 2% by mass or more, and still more preferably 3% by mass or more. When the total content of component (A) is 10% by mass or less relative to the total amount of the external composition, preferably 9% by mass or less, and still more preferably 8% by mass or less. The total content of component (A) relative to the total amount of the external composition is preferably 1% by mass to 10% by mass, more preferably 2% by mass to 10% by mass, and still more preferably 3% by mass to 8% by mass.

[0063] [(B) diol having three carbon atoms]

[0064] As the diol having three carbon atoms used in the present invention, there is no particular limitation as long as it is used as a component of a topical preparation for skin in the fields of pharmaceuticals, quasi-drugs, or cosmetics. Although the diol having three carbon atoms is not limited, it is preferably 1,3-propanediol (CAS No.: 504-63-2, English name: 1,3-Dihydroxypropane or Trimethylene Glycol) or propylene glycol (CAS No.: 57-55-6, English name: 1,2-Dihydroxypropane, alias: 1,2-propanediol). For example, either one or both of 1,3-propanediol and propylene glycol can be used as the component (B). Such diols having three carbon atoms can also directly use commercially available products. It should be noted that from the viewpoints of alleviating irritation to the skin, improving the feeling of use, and suppressing coloring, it is preferable to combine 1,3-propanediol and propylene glycol.

[0065] In the topical composition of the first invention, the total content of the component (B) relative to the total amount of the topical composition is 30% by mass or more, preferably 35% by mass or more, more preferably 40% by mass or more, and further preferably 45% by mass or more.

[0066] The total content of the component (B) relative to the total amount of the topical composition is preferably 90% by mass or less, more preferably 85% by mass or less, and further preferably 80% by mass or less.

[0067] The total content of the component (B) relative to the total amount of the topical composition of the first invention is preferably 35 to 90% by mass, more preferably 40 to 85% by mass, and further preferably 45 to 80% by mass.

[0068] In the topical composition of the first invention, the ratio of the content of the component (B) to the component (A) is not particularly limited. Relative to 1 part by mass of the total content of the component (A), it is preferably 3 to 300 parts by mass, more preferably 3 to 30 parts by mass, and further preferably 5 to 25 parts by mass.

[0069] [(C) Water]

[0070] The topical composition of the first invention is a liquid composition containing water. The proportion of water is not limited, but relative to the topical composition, it is preferably 0.1% by mass or more, further preferably 1% by mass or more, and most preferably more than 1% by mass. Although not limited, more than 1% by mass can be, for example, values such as 1.01% by mass or more, 1.1% by mass or more, etc. The proportion of water relative to the topical composition is 20% by mass or less. It is preferably 15% by mass or less, and more preferably 10% by mass or less.

[0071] The total content of the component (C) relative to the total amount of the external composition of the first invention is preferably 1% by mass to 15% by mass, more preferably more than 1% by mass and 10% by mass or less, and still more preferably 2 to 10% by mass.

[0072] 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. Relative to 1 part by mass of the total content of the component (A), it is preferably 0.1 to 10 parts by mass, more preferably 0.125 to 8 parts by mass, and still more preferably 0.2 to 5 parts by mass.

[0073] In the present invention, even in a composition containing a small amount of water, precipitation of ascorbic acid or its salt can be inhibited. Moreover, an external composition with excellent stability can be provided. However, from the viewpoint of inhibiting precipitation of ascorbic acid at low temperatures, it is preferably incorporated even in a small amount.

[0074] [Ethoxydiglycol (diethylene glycol monoethyl ether)]

[0075] In the present invention, from the viewpoint of mainly improving stability, it does not contain ethoxydiglycol, or even if it contains, it is less than 30% by mass. The ethoxydiglycol contained in the external composition in an amount less than 30% by mass is not particularly limited as long as it can be used as a component for external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics.

[0076] 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% by mass, preferably 20% by mass or less, more preferably 10% by mass or less, still more preferably 5% by mass or less, and the external composition may not contain ethoxydiglycol.

[0077] 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 still more preferably 0 to 5% by mass.

[0078] 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). Additionally, depending on the circumstances, it can also be set to 0.001 to 10 parts by mass or 0.01 to 5 parts by mass.

[0079] [pH]

[0080] From the viewpoints of the stability of the component (A), low irritation to the skin and mucous membranes, and good skin feel in use, the first external composition of the present invention is preferably in the acidic range of pH 1.5 to 4.5, more preferably pH 2 to 4.

[0081] The external composition of the first invention contains a specified amount of component (A), component (B), and component (C), and by specifying the content of ethoxydiglycol and further setting the pH to 4.5 or less, an external composition with good stability is obtained.

[0082] [Diethylene glycol ether]

[0083] In the present invention, from the viewpoint of mainly improving stability, it may contain a diethylene glycol ether other than ethoxydiglycol, or may not contain it. When contained, the total amount of diethylene glycol ethers together with ethoxydiglycol is preferably less than 40% by mass. Here, the diethylene glycol ether other than ethoxydiglycol is not particularly limited as long as it is used as a component of a skin external preparation in the fields of pharmaceuticals, quasi-drugs, or cosmetics. It is sufficient to dissolve 10 g or more in 100 g of water. Substances with a polymerization degree of 2 or less can be exemplified. Specifically, diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, diethylene glycol mono-isobutyl ether, diethylene glycol dimethyl ether, ethylene glycol monobutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, triethylene glycol monobutyl ether, tetraethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether, etc. can be exemplified. In addition, diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, diethylene glycol mono-isobutyl 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 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, dipropylene glycol monopropyl ether are typical examples.

[0084] These diethylene glycol ethers can be used singly or in combination of two or more.

[0085] In the external composition of the first invention, the total content of diethylene glycol 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, and still more preferably 10% by mass or less. The external composition may also not contain a diethylene glycol ether.

[0086] The total content of diethylene glycol ethers containing ethoxydiglycol is preferably 0 or more and less than 40% by mass, more preferably 0 or more and less than 30% by mass, and further preferably about 10% by mass or more and 0 or more.

[0087] In the external composition of the first invention, the ratio of the content of the diethylene glycol ether component relative to the (A) component 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 (A) component. Additionally, depending on the circumstances, it may also be 0.001 to 20 parts by mass or 0.01 to 10 parts by mass.

[0088] The external composition of the first invention contains a specified amount of the (A) component, (B) component, and (C) component, and by regulating the total content of diethylene glycol ether, the pH is set to 4.5 or less, thereby enabling the obtainment of an external composition with better stability.

[0089] [Lower alcohol]

[0090] From the viewpoints of improving the usability, stability, and promoting percutaneous absorption, as long as the effects of the present invention are not hindered, in addition to the above-mentioned (A) component, (B) component, and (C) component, and diethylene glycol ethers such as ethoxydiglycol when contained, the external composition of the first invention may further contain a lower alcohol. The lower alcohol used in the present invention is not particularly limited as long as it is a component used as a topical skin agent in the fields of pharmaceuticals, quasi-drugs, or cosmetics. In this specification, "lower alcohol" refers to an alcohol having C 1 -C 6 Among them, an alcohol having C 1 -C 3 can be particularly preferably used. As such examples, in addition to ethanol, methanol, n-propanol, isopropanol, etc. can also be cited.

[0091] In the external composition of the first invention, when the lower alcohol is contained, the content of the lower alcohol 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, further preferably 0.25% by mass or more, still further 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, still further preferably 20% by mass or less.

[0092] 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, still further preferably 1 to 20% by mass, and most preferably 3 to 20% by mass.

[0093] [Butylene glycol]

[0094] From the viewpoints of improving the usability, stability, and promoting percutaneous absorption, as long as the effects of the present invention are not impaired, the external composition of the present invention may contain, in addition to the above components (A), (B), and (C), and diglycol ethers such as ethoxydiglycol when contained, butanediol (1,3 - butanediol).

[0095] In the external composition of the first invention, when butanediol is contained, the content of butanediol 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 still more preferably 0.25% by mass or more. The content of butanediol is preferably 55% by mass or less, more preferably 50% by mass or less, and still more preferably 45% by mass or less.

[0096] The content of butanediol in the external composition of the first invention is preferably 0.01 - 55% by mass, more preferably 0.1 - 50% by mass, and still more preferably 0.25 - 45% by mass.

[0097] [pH adjuster]

[0098] From the viewpoints of improving the usability, stability, and promoting percutaneous absorption, as long as the effects of the first invention are not impaired, the external composition of the first invention may contain, in addition to the above components (A), (B), and (C), and diglycol ethers such as ethoxydiglycol when contained, a pH adjuster.

[0099] As the pH adjuster used in the first invention, compounds that are usually used as components of skin external preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used. Although not particularly limited, examples include pH adjusters having amines (such as asparagine or its salts, ε - aminocaproic acid or its salts, glutamic acid or its salts, aminoethylsulfonic acid or its salts, monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, arginine, lysine, L - carnitine, low molecular weight betaine, preferably low molecular weight betaine, more preferably trimethylglycine), organic acid salts (such as sodium lactate, sodium acetate, sodium citrate, sodium succinate, sodium oxalate, calcium gluconate, sodium pyrrolidonecarboxylate, etc.), inorganic acid salts (such as sodium metabisulfite, potassium metabisulfite, sodium phosphate, potassium nitrate, sodium borate, preferably sodium metabisulfite), basic amino acids and their salts (arginine, lysine, or histidine and their salts), 3 - O - ethylascorbic acid or its salts, etc.

[0100] In the external composition of the first invention, the total content of the pH adjuster relative to the total amount of the external composition is not particularly limited, preferably 0.01% by mass or more, more preferably 0.05% by mass or more. Relative to the total amount of the external composition, the total content of the pH adjuster is preferably 10% by mass or less, more preferably 5.0% by mass or less. Relative to the total amount of the external composition, the content of the pH adjuster having an amine or an amino group is preferably 0.01% by mass to 10% by mass, more preferably 0.05% by mass to 5.0% by mass.

[0101] In the external composition of the first invention, the ratio of the content of the pH adjuster relative to the (A) component is not particularly limited. Relative to 1 part by mass of the total content of the (A) component, it 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.

[0102] [Other components]

[0103] In the external composition of the present invention, in addition to the above-mentioned (A) component, (B) component, (C) component, and ethoxydiglycol in an amount less than a certain amount when contained, for the purpose of enhancing or supplementing various functions of ascorbic acid and for adding other useful functions, various components such as whitening components, anti-inflammatory components, antibacterial components, cell activation components, firming components, antioxidant components, acne improvement components, anti-aging components, biological component synthesis promoting components such as collagen, blood circulation promoting components, moisturizing components, anti-aging components, etc. may be combined and formulated, one or more than two kinds. Preferably, it is one or more than two kinds of components such as whitening components, anti-inflammatory components, antibacterial components, cell activation components, firming components, antioxidant components, anti-aging components, or moisturizing components. In the combination of these components, as a particularly preferred combination, a combination with a whitening component, a combination of a whitening component and an antioxidant component, each combination with an antioxidant component, a combination with an anti-aging component, and each combination of a whitening component and an anti-aging component can be cited. As these respective components, substances that have been used in the past and can be used in the future as components of skin external preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics are not particularly limited, and any substance can be appropriately selected and used.

[0104] Based on the above-mentioned respective components, the external composition of the present invention may further contain a surfactant, a solubilizing component, an oil, a sugar, or a transdermal absorption promoting component. In particular, by containing a surfactant, a solubilizing component, or an oil, the stability, effectiveness, and usability of ascorbic acid in an aqueous solvent can be further improved.

[0105] In the external composition of the present invention, within the range of the amount and quality that do not impair the appearance stability, viscosity and other qualities and do not impair the effects of the present invention, various components generally used as components of external preparations can be formulated as needed in the fields of pharmaceuticals, quasi-drugs or cosmetics, such as amino acids, irritation-reducing agents, thickeners, preservatives, ultraviolet ray protectants, coloring agents, dispersants, additional pH adjusters, fragrances, etc. It should be noted that these components can be used alone or in any combination of two or more.

[0106] The external composition of the first invention contains (A) at least 10% by mass or less of at least one selected from ascorbic acid and salts of ascorbic acid, (B) 30% by mass or more of a diol having three carbon atoms, (C) 20% by mass or less of water, and the content of ethoxydiglycol is less than 30%, and the pH is 4.5 or less. If necessary, the above-mentioned optional components are mixed, and further, other solvents or bases of commonly used external preparations are formulated as needed, and various desired forms such as paste, mousse, gel, liquid, milk liquid, cream, sheet (substrate-supported), aerosol, spray, etc. can be prepared. These can be manufactured by the methods commonly used in the art.

[0107] The external 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 using ultraviolet-visible absorbance measurement method, using a spectrophotometer or a photoelectric spectrophotometer UV-2450 (manufactured by Shimadzu Corporation), the transmittance at a wavelength of 700 nm is in the range of 80 to 100%, preferably 85 to 100%, more preferably 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 measurement method is more specifically based on the method described in "[16th Revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods - Optical Measurement Methods 2.24 Ultraviolet-Visible Absorbance Measurement Method]".

[0108] [Viscosity]

[0109] The external composition of the present invention can be prepared as a composition having an appropriate viscosity as desired when used as an external composition particularly for use on the skin. The viscosity of the external composition of the present invention is not particularly limited. For example, when measured at 25 °C using an E-type viscometer, the viscosity is generally 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. More specifically, the viscosity measurement method is 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. Method 2 Rotational Viscometer Method 2.1.3 Cone - Plate Type Rotational Viscometer (Cone - Plate Viscometer)".

[0110] [Use]

[0111] 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, the effects of acne prevention, treatment, and antioxidation. And by applying it to the skin, it sometimes exhibits the effects of improving the transparency of the skin, maintaining moisture, making the skin texture neat, and suppressing roughness. In addition, in addition to sometimes exhibiting the effects of making pores less obvious and whole muscle moisturizing, it can also be used for the prevention and treatment of liver spots.

[0112] The external composition of the present invention can be, for example, various external compositions belonging to the fields of basic cosmetics such as beauty essences, lotions, sunscreen creams, emulsions, day creams, milks, oils, and face masks; beauty cosmetics such as foundations, lipsticks, lip balms, mascaras, eyeliner creams, eyeliners, eyebrow powders, and nail cosmetics; cleansing agents such as cleansing pigments, facial cleansers, and body cleansers; antiperspirants, tinea pedis treatment agents, antipruritics, wound treatment agents, wipes, detergents, anti-inflammatory analgesics, acne treatment agents, hemorrhoid agents, bactericidal disinfectants, whitening agents, ultraviolet ray protectants, etc., belonging to the fields of cosmetics, external pharmaceuticals, or quasi-external pharmaceuticals. From the perspective of the effects on the skin, the present invention is preferably used in products for external application to the skin (preparations for external skin use).

[0113] [Stabilization Method]

[0114] Furthermore, the present invention also includes a stabilization method for at least one selected from (A) ascorbic acid and salts of ascorbic acid. In the present invention, according to the stabilization method of ascorbic acid, by using in combination (A) at least one selected from ascorbic acid and salts of ascorbic acid at 10% by mass or less, (B) a diol having three carbon atoms at 30% by mass or more, and (C) water at 20% by mass or less, and making the content of ethoxydiglycol less than 30% and the pH 4.5 or less, a stable preparation can be formed while containing ascorbic acid. That is, the present invention relates to a method for imparting stability to a topical composition containing (A) at least one selected from ascorbic acid and salts of ascorbic acid by using in combination (A) at least one selected from ascorbic acid and salts of ascorbic acid at 10% by mass or less, (B) a diol having three carbon atoms at 30% by mass or more, and (C) water at 20% by mass or less, and making the content of ethoxydiglycol less than 30% and the pH 4.5 or less. Here, stabilization is not limited, but for example, it means ensuring stability at high temperature or low temperature. Specifically, at least when the topical composition is stored at 4°C for 1 week, precipitation of ascorbic acid or its salt is inhibited, or appearance changes such as coloring are inhibited after storage at 50°C or storage at 40°C for a certain period of time.

[0115] In the method of the present invention, the contents, ratios, etc. of (A) at least one selected from ascorbic acid and salts of ascorbic acid, (B) a diol having three carbon atoms, (C) water, and ethoxydiglycol are the same as the substances used in the topical composition. In addition, the substances obtained by this method can be used once to several times a day according to the use, etc., in a known or conventional usage and dosage.

[0116] The second aspect of the present invention is the case where at least one selected from ascorbic acid and salts of ascorbic acid is 10 to 25% by mass (hereinafter also referred to as the second invention).

[0117] The topical composition of the second invention contains the following components,

[0118] (A) at least one selected from ascorbic acid and salts of ascorbic acid at 10 to 25% by mass

[0119] (B) a diol having three carbon atoms at 30 to 90% by mass in the components other than (A) and (C); and (C) water,

[0120] 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.

[0121] The topical composition of the second invention is very stable in a relatively high concentration range of (A) at least one selected from ascorbic acid and salts of ascorbic acid and has excellent percutaneous absorbability.

[0122] [(A) is at least one selected from ascorbic acid and salts of ascorbic acid]

[0123] In the present invention, ascorbic acid commercially available as a component of a topical preparation for the skin in the fields of pharmaceuticals, quasi-drugs or cosmetics can be used. These are usually the L-form.

[0124] Salts of ascorbic acid can also be used. Here, the salts of ascorbic acid are the same as the substances defined in the case of the first invention. Although not limited, for example, salts formed with organic bases (e.g., salts of tertiary amines such as trimethylamine salt, triethylamine salt, monoethanolamine salt, triethanolamine salt, pyridine salt, etc., basic ammonium salts such as arginine, etc.), salts formed with inorganic bases (e.g., alkali metal salts such as ammonium salt, sodium salt, potassium salt, etc., alkaline earth metal salts such as calcium salt, magnesium salt, etc., aluminum salt, etc.) and the like can be mentioned. Particularly preferred salts of ascorbic acid are sodium salt and potassium salt. Specifically, sodium ascorbate, sodium ascorbate monophosphate, sodium ascorbate diphosphate, sodium ascorbate triphosphate, sodium ascorbate-2-sulfate, etc. can be mentioned.

[0125] In the present invention, ascorbic acid or its salts can be used singly or in combination of two or more.

[0126] In the topical composition of the second invention, the total content of component (A) relative to the total amount of the topical composition is appropriately set according to the balance with other components. There is no particular limitation as long as the total content of component (A) is 10 to 25% by mass relative to the total amount of the topical composition.

[0127] [(B) a diol having three carbon atoms]

[0128] As the diol having three carbon atoms used in the topical composition of the second invention, there is no particular limitation as long as it is a substance used as a component of a topical preparation for the skin in the fields of pharmaceuticals, quasi-drugs or cosmetics. It is the same as the substance defined in the case of the first invention. Although the diol having three carbon atoms is not limited, 1,3-propanediol or propylene glycol is preferred. For example, one or both of 1,3-propanediol and propylene glycol can be used as component (B). Such diols having three carbon atoms can also be directly used as commercially available products. It should be noted that from the viewpoints of alleviating irritation to the skin, improving the feeling of use, and suppressing coloring, it is preferred to combine 1,3-propanediol and propylene glycol.

[0129] In the topical composition of the second invention, the total content of component (B) relative to the total amount of the topical composition is 10% by mass or more, preferably 15% by mass or more, more preferably 20% by mass or more, and further preferably 25% by mass or more.

[0130] The total content of component (B) relative to the total amount of the external composition is preferably 90% by mass or less, more preferably 85% by mass or less, still more preferably 80% by mass or less, and even more preferably 70% by mass or less.

[0131] The total content of component (B) relative to the total amount of the external composition is preferably 10 - 90% by mass, more preferably 15 - 85% by mass, still more preferably 20 - 80% by mass, and even more preferably 25% by mass - 70% by mass.

[0132] In the external composition of the second invention, the ratio of the content of component (B) to component (A) is not particularly limited, and is preferably 0.5 - 10 parts by mass, more preferably 0.75 - 8 parts by mass, and still more preferably 1 - 7 parts by mass with respect to 1 part by mass of the total content of component (A).

[0133] In the external composition of the second invention, the content of component (B) relative to the components other than component (A) and the following component (C) is preferably 30 - 95% by mass, more preferably 40 - 90% by mass, and even more preferably 50 - 85% by mass.

[0134] [(C) Water]

[0135] The external composition of the second invention is a liquid composition containing water. The proportion of water is not limited, and is preferably 0.01% by mass - 60% by mass, more preferably 1% by mass - 50% by mass, still more preferably 3% by mass - 40% by mass, and particularly preferably 5% by mass - 30% by mass with respect to the external composition.

[0136] In the external composition of the second invention, the ratio of the content of component (C) to component (A) is not particularly limited, and is preferably 0.2 - 5 parts by mass, more preferably 0.5 - 2 parts by mass, and still more preferably 0.6 - 1.8 parts by mass with respect to 1 part by mass of the total content of component (A).

[0137] [Ethoxydiglycol (diethylene glycol monoethyl ether)]

[0138] 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 fields of pharmaceuticals, quasi-drugs, or cosmetics.

[0139] 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% by mass, preferably 20% by mass or less, more preferably 10% by mass or less, still more preferably 5% by mass or less, and the external composition may also not contain ethoxydiglycol.

[0140] 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 further preferably about 0 to 5% by mass.

[0141] In the external composition of the second invention, the ratio of the content of the ethoxydiglycol component relative to the component (A) is preferably 0 to 10 parts by mass, more preferably 0 to 5 parts by mass, per 1 part by mass of the total content of the component (A). Additionally, depending on the situation, it may also be 0.001 to 10 parts by mass or 0.01 to 5 parts by mass.

[0142] [pH]

[0143] The external composition of the present invention usually only needs to have a liquid property of pH 1 to 8. From the viewpoints of the stability of ascorbic acid, low irritation to the skin and mucous membranes, and good skin feel, it is preferably pH 2 to 7, more preferably pH 2 to 6, still more preferably pH 2 to 5, and particularly preferably the acidic range of pH 2 to 4.5.

[0144] [Diethylene glycol ether]

[0145] In the present invention, from the viewpoint of improving stability, it may or may not contain a diethylene glycol ether other than ethoxydiglycol. When it contains, the total content of diethylene glycol ethers including ethoxydiglycol is preferably less than 40% by mass. Here, the diethylene glycol ether other than ethoxydiglycol is not particularly limited as long as it is a substance used as a component of a topical skin preparation in the fields of pharmaceuticals, quasi-drugs, or cosmetics. It is sufficient to dissolve 10 g or more in 100 g of water. Substances with a polymerization degree of 2 or less can be exemplified. Specifically, diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, diethylene glycol mono-isobutyl ether, diethylene glycol dimethyl ether, ethylene glycol monobutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, triethylene glycol monobutyl ether, tetraethylene glycol monobutyl ether, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monomethyl ether, dipropylene glycol monoethyl ether, dipropylene glycol monopropyl ether, etc. can be exemplified. In addition, diethylene glycol monomethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, diethylene glycol mono-isobutyl 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 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, dipropylene glycol monopropyl ether are typical examples.

[0146] These diethylene glycol ethers can also be used singly or in combination of two or more.

[0147] In the topical composition of the second invention, the total content of diethylene glycol ethers containing ethoxydiglycol is preferably less than 40% by mass, more preferably 30% by mass or less, further preferably less than 10% by mass, still more preferably 10% by mass or less, and the topical composition may not contain a diethylene glycol ether.

[0148] The total content of diethylene glycol ethers containing ethoxydiglycol is preferably 0 or more and less than 40% by mass, more preferably 0 or more and less than 30% by mass, and further preferably about 0 or more and 10% by mass.

[0149] In the topical 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, per 1 part by mass of the total content of the component (A). Additionally, depending on the situation, it may also be 0.001 to 20 parts by mass, or 0.01 to 10 parts by mass.

[0150] The external composition of the second invention contains a specified amount of component (A), component (B), and component (C), specifies the total content of diethylene glycol ethers, and sets the pH to 1.5 to 4.5 or lower, more preferably pH 2 to 4.5 or lower, so that an external composition with better stability can be obtained.

[0151] [Lower alcohol]

[0152] From the viewpoints of improving the usability, stability, and promoting percutaneous absorption, as long as the effects of the present invention are not hindered, the external composition of the second invention may contain a lower alcohol in addition to the above-mentioned component (A), component (B), component (C), and diethylene glycol ethers such as ethoxydiglycol in the case of containing. 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 topical skin preparation in the fields of pharmaceuticals, quasi-drugs, or cosmetics. In this specification, "lower alcohol" refers to an alcohol having C 1 -C 6 . Among them, an alcohol having C 1 -C 3 can be particularly preferably used. As such examples, in addition to ethanol, methanol, n-propanol, isopropanol, etc. can be cited.

[0153] In the external composition of the second invention, when contained, the content of the lower alcohol 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, further preferably 0.25% by mass or more, still 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, still more preferably 20% by mass or less.

[0154] 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, still more preferably 1 to 20% by mass, and most preferably 3 to 20% by mass.

[0155] [Butylene glycol]

[0156] From the viewpoints of improving the usability, stability, and promoting percutaneous absorption, as long as the effects of the present invention are not hindered, the external composition of the present invention may also contain butylene glycol (1,3-butylene glycol) in addition to the above-mentioned component (A), component (B), component (C), and diethylene glycol ethers such as ethoxydiglycol in the case of containing.

[0157] 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 still more 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 still more preferably 30% by mass or less.

[0158] 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 still more preferably 0.25 to 30% by mass.

[0159] [pH adjuster]

[0160] From the viewpoints of improving the usability, stability, and promoting percutaneous absorption, as long as the effects of the second invention are not hindered, the external composition of the second invention may contain a pH adjuster in addition to the above components (A), (B), and (C), and diethylene glycol ethers such as ethoxydiglycol when contained.

[0161] As the pH adjuster used in the second invention, compounds that are usually used as components of external skin preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be used. Although not particularly limited, examples include pH adjusters having amines (e.g., asparagine or its salt, ε-aminocaproic acid or its salt, glutamic acid or its salt, aminoethylsulfonic acid or its salt, monoethanolamine, triethanolamine, diisopropanolamine, triisopropanolamine, arginine, lysine, L-carnitine, low-molecular-weight betaine, preferably low-molecular-weight betaine, more preferably trimethylglycine), organic acid salts (e.g., sodium lactate, sodium acetate, sodium citrate, sodium succinate, sodium oxalate, calcium gluconate, sodium pyrrolidonecarboxylate, etc.), inorganic acid salts (e.g., sodium metabisulfite, potassium metabisulfite, sodium phosphate, potassium nitrate, sodium borate, preferably sodium metabisulfite), basic amino acids and their salts (arginine, lysine, or histidine and their salts), 3-O-ethylascorbic acid or its salt, etc.

[0162] In the external composition of the second invention, the total content of the pH adjuster relative to the total amount of the external composition is not particularly limited, and is preferably 0.01% by mass or more, more preferably 0.05% by mass or more. Relative to the total amount of the external composition, the total content of the pH adjuster is preferably 20% by mass or less, more preferably 10% by mass or less. Relative to the total amount of the external composition, the content of the pH adjuster having an amine or amino group is preferably 0.01% by mass to 20% by mass, more preferably 0.05% by mass to 10% by mass.

[0163] In the external composition of the second invention, the ratio of the content of the pH adjuster relative to the component (A) is not particularly limited. Relative to 1 part by mass of the total content of the component (A), it is preferably 0.00001 to 20 parts by mass, more preferably 0.0001 to 20 parts by mass, still more preferably 0.0005 to 10 parts by mass, still more preferably 0.005 to 5 parts by mass, and most preferably 0.01 to 1 part by mass.

[0164] [Other components]

[0165] In the external composition of the second invention, in addition to the above-mentioned components (A), (B), and (C), and ethoxydiglycol in an amount less than a certain amount when contained, for the purpose of enhancing or supplementing various functions of ascorbic acid and for adding other useful functions, various components such as whitening components, anti-inflammatory components, antibacterial components, cell activation components, firming components, antioxidant components, acne improvement components, anti-aging components, components that promote the synthesis of biological components such as collagen, blood circulation promoting components, moisturizing components, and anti-aging components can be combined and formulated in one or more than two kinds. It is preferably one or more than two kinds of components selected from whitening components, anti-inflammatory components, antibacterial components, cell activation components, firming components, antioxidant components, anti-aging components, or moisturizing components. Among these combinations of components, as particularly preferred combinations, there can be mentioned combinations with whitening components, combinations of whitening components and antioxidant components, various combinations with antioxidant components, combinations with anti-aging components, and various combinations of whitening components and anti-aging components. As these various components, as long as they have been used in the past and can be used in the future as components of skin external preparations in the fields of pharmaceuticals, quasi-drugs, or cosmetics, there is no particular limitation, and any substance can be appropriately selected and used.

[0166] Based on the above-mentioned various components, the external composition of the present invention can further contain surfactants, solubilizing components, oils and fats, sugars, or transdermal absorption promoting components. In particular, by incorporating surfactants, solubilizing components, or oils and fats, the stability, effectiveness, and usability of ascorbic acid in aqueous solvents can be further improved.

[0167] In the external composition of the present invention, within the range of amounts and qualities that do not impair the appearance stability, viscosity, etc. of the product and do not impair the effects of the present invention, various components generally used as external preparation components in the fields of pharmaceuticals, quasi-drugs, or cosmetics can be incorporated as needed, such as amino acids, irritation reducing agents, thickening agents, preservatives, ultraviolet protectants, coloring agents, dispersants, additional pH adjusters, fragrances, etc. It should be noted that these components can be used alone or in any combination of two or more.

[0168] The external composition of the second invention can be prepared by containing (A) at least one selected from ascorbic acid and salts of ascorbic acid in an amount of 10 to 25% by mass; (B) a diol having three carbon atoms in an amount of 30 to 90% by mass in components other than (A) and (C); and (C) water, and the content of ethoxydiglycol is less than 30%, (C) / (A) = 0.2 to 5, and the pH is 2.0 to 6.0. If necessary, the above-mentioned optional components are mixed, and further, other solvents, bases of commonly used external preparations, etc. are added as needed, whereby various desired forms such as paste, mousse, gel, liquid, milk liquid, cream, sheet (substrate-supported), aerosol, spray, etc. can be prepared. These can be manufactured by the usual methods in the art.

[0169] The external composition of the present invention is particularly preferably a transparent or even translucent composition in which ascorbic acid and / or its salt is solubilized. Here, "solubilization" is defined as follows. That is, for example, by using ultraviolet-visible absorbance measurement method, using a spectrophotometer or a photoelectric spectrophotometer UV-2450 (manufactured by Shimadzu Corporation), as the transmittance at a wavelength of 700 nm, the transmittance is in the range of 80 to 100%, preferably 85 to 100%, more preferably 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 measurement method is more specifically based on the method described in "The 16th Revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Optical Measurement Methods 2.24 Ultraviolet-Visible Absorbance Measurement Method".

[0170] [Viscosity]

[0171] The external composition of the present invention can be prepared as a composition having a desired moderate viscosity when used as an external composition particularly applied to the skin. The viscosity of the external composition of the present invention is not particularly limited. For example, when measured at 25 °C using an E-type viscometer, the viscosity 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 "The 16th Revised Japanese Pharmacopoeia [B] General Test Methods 2. Physical Test Methods Other Physical Test Methods 2.53 Viscosity Measurement Method 2. Method 2 Rotating Viscometer Method 2.1.3 Cone-Plate Type Rotating Viscometer (Cone Plate Viscometer)".

[0172] [Use]

[0173] 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, the effects of acne prevention, treatment, and antioxidant. Moreover, by applying it to the skin, it sometimes exerts the effects of improving the transparency of the skin, maintaining moisture, making the texture neat, and suppressing roughness. In addition, it sometimes exerts effects such as making pores less obvious, skin conditioning and moisturizing, etc. Besides, it can also be used for the prevention and treatment of chloasma.

[0174] The external composition of the present invention can be, for example, basic cosmetics such as skin lotion, lotion, sunscreen, emulsion, day cream, milk, oil, and mask; beauty cosmetics such as foundation, lipstick, lip balm, mascara, eyeliner, eyeliner pencil, eyebrow powder, and nail cosmetics; cleansing agents such as cleansing pigment, facial cleanser, and body wash; various external compositions in the fields of cosmetics, external pharmaceuticals, or quasi-external pharmaceuticals, such as anti-axillary odor agents, foot odor treatment agents, antipruritics, wound treatment agents, cleaning agents, detergents, anti-inflammatory analgesics, acne treatment agents, agents for hemorrhoids, bactericidal disinfectants, whitening agents, and ultraviolet ray protectants. Considering the effects on the skin, the present invention is preferably used in external products such as skin external agents (preparations for the outer skin).

[0175] [Stabilization method]

[0176] Moreover, the present invention also includes a stabilization method of (A) at least one selected from ascorbic acid and salts of ascorbic acid. In the present invention, according to the stabilization method of ascorbic acid, by containing (A) at least one selected from ascorbic acid and salts of ascorbic acid in an amount of 10 to 25% by mass; (B) a diol having three carbon atoms in an amount of 30 to 90% by mass in the components other than (A) and (C); and (C) water, and the content of ethoxydiglycol being less than 30%, (C) / (A)=0.2 to 5, and adjusting the pH to 2.0 to 6.0, a stable preparation containing ascorbic acid can be formed. That is, the present invention relates to a method of imparting stability to an external composition containing (A) at least one selected from ascorbic acid and salts of ascorbic acid by containing (A) at least one selected from ascorbic acid and salts of ascorbic acid in an amount of 10 to 25% by mass; (B) a diol having three carbon atoms in an amount of 30 to 90% by mass in the components other than (A) and (C); and (C) water, and the content of ethoxydiglycol being less than 30%, (C) / (A)=0.2 to 5, and adjusting the pH to 2.0 to 6.0. Here, although not limited, stabilization means, for example, ensuring stability at high temperature or low temperature. Specifically, it means suppressing the precipitation of ascorbic acid or its salt when the external composition is stored at 4°C for 1 week, or suppressing appearance changes such as coloring after storage at 50°C or storage at 40°C for a certain period.

[0177] In the method of the present invention, at least one selected from ascorbic acid and salts of ascorbic acid, a diol having three carbon atoms, water, and the content and ratio of ethoxydiglycol are the same as the conditions used in the external composition. In addition, the substance obtained by this method can be used once to several times a day according to the use and the like, and used in a known or conventional usage and dosage.

[0178] Examples

[0179] 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%.

[0180] External compositions having the compositions shown in Tables 1 to 6 were prepared according to a conventional method. Thereafter, these compositions were subjected to tests according to each test item.

[0181] [Ascorbic acid coloring inhibition confirmation test]

[0182] The presence or absence of coloring inhibition after storage at 40 °C or 50 °C of the external compositions of several examples and comparative examples of the present invention was evaluated visually or using a color difference meter. Specifically, according to the prescriptions (mass%) described 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 into a transparent glass bottle and left standing in a constant temperature and humidity machine at 40 °C or 50 °C for 1 week (denoted as 1W) or 4 weeks (denoted as 4W). During each measurement period, the container was taken out of the constant temperature machine and evaluated after being equilibrated at 25 °C. The presence or absence and degree of coloring were determined by measurement of each test solution based on visual observation or using a color difference meter.

[0183] For the measurement based on the color difference meter, 1 mL of the test solution was placed 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 used Δb* when purified water was used as the blank. The change in color difference was calculated according to the following calculation formula.

[0184] (Change amount of color difference (Δb value)) = (Measured value of the test solution after heat preservation (b value after accelerated test)) - (Measured value of the test solution before heat preservation (b value before accelerated test))

[0185] The b value is used as an index indicating transparency. Therefore, the smaller the Δb value, the less the coloring. In addition, when the ratio of Δb between the two is 1.4 or less, the coloring difference is not strongly felt. On the other hand, when it exceeds 1.4, the coloring difference can be clearly observed, and a quality defect occurs. Therefore, it is determined whether the ratio when the Δb value of the sample with no change in coloring is set to 1 is 1.4 or less to judge the presence or absence of coloring.

[0186] [Ascorbic acid precipitation inhibition confirmation test]

[0187] Visual evaluation was carried out on the presence or absence of ascorbic acid precipitation when the external use compositions of several examples and comparative examples of the present invention were stored at low temperature. Specifically, according to the formulations (mass %) described in various formulation tables, ascorbic acid was added to the mixed solution of various components, heated and mixed at 60 °C for 10 minutes to dissolve it, and the composition was prepared. The prepared composition was filled into a transparent glass bottle, left standing under light-shielded conditions at 4 °C, and stored for 1 week or 4 weeks. Each test solution was visually observed to determine whether crystal precipitation occurred.

[0188] <Evaluation criteria>

[0189] ○: The state where no precipitate can be visually confirmed; ×: The state where a precipitate can be visually confirmed.

[0190] [Ascorbic acid percutaneous absorption test]

[0191] The percutaneous absorption of the external use compositions of several examples and comparative examples of the present invention was verified. By improving percutaneous absorption, ascorbic acid penetrates into the muscle, thereby expecting a higher anti-aging effect as a composition. That is, in some cases, the effect of ascorbic acid can affect the deep part of the stratum corneum.

[0192] The percutaneous absorption of ascorbic acid in the external use compositions prepared in the examples and comparative examples was confirmed by evaluation measurement based on stratum corneum removal.

[0193] Specifically, first, the amount of ascorbic acid in the stratum corneum of the components that penetrated into the skin of the upper arm and forearm of healthy subjects was confirmed by tape stripping. Two male healthy subjects who freely consented to participate in the test were used as the subjects. A gauze soaked with 750 μL of the external use composition of the example or comparative example was attached to the inner part of the upper arm of the subject at 1.5 cm × 1.5 cm and left standing for 5 minutes. After removing the gauze, the sample remaining on the skin surface was removed using a new gauze and left standing for 30 minutes. This time was used as the penetration time of the sample. Thereafter, using an adhesive tape (manufactured by Sumitomo 3M), tape stripping was carried out 7 times continuously from the coated part to strip the horny cells, and all the layers of the obtained tape were used as the specimens for measurement. Through preliminary tests, it was confirmed that the necessary amount of horny cells could be stripped each time the tape was stripped and no inflammation or pain occurred after tape stripping, and thus the number of tape stripping was set.

[0194] The obtained measurement specimen was extracted with 1 mL of an extraction solvent, which was a mixture (1:1:1000) of Tritonx-100 (manufactured by MP Biomedicals), mercaptoethanol (manufactured by Wako Pure Chemical Industries, Ltd.), and purified water. The extraction solution from which foreign substances had been removed by a 0.45-μm syringe filter (manufactured by GL Science) was used to measure the permeation amount (μg / mL) of ascorbic acid by HPLC. The measurement was performed by HPLC manufactured by Agilent (mobile phase: acetonitrile / 0.02 M phosphoric acid solution (pH 3.0) (1:9), detection wavelength of absorbance: 270 nm) equipped with a reversed-phase column (CAPCELL PAK C18SG120, manufactured by Shiseido) to measure the amount of L-ascorbic acid contained in the solution. The value obtained by averaging the measured values of the measurement specimens taken from three positions on the arms of two subjects was used as the permeation amount (μg / cm 2 ) and compared as a result.

[0195] It should be noted that the HPLC-based detection of ascorbic acid was performed using an ultraviolet spectrophotometer with a reversed-phase column (CAPCELL PAK C18SG120, manufactured by Shiseido) at a wavelength of 270 nm, and the content was calculated based on a standard curve.

[0196] (Examples 1-1 to 1-6, Comparative Examples 1-1 to 1-3)

[0197] External compositions of the examples and comparative examples having the compositions shown in Table 1 were prepared according to a conventional method. Among the evaluation items, the ratio of Δb was based on the color difference value of the external composition in Example 1-1 (1), and the ratio of the comparative value was recorded. That is, the ratio of stability represents the ratio of Δb.

[0198] The results of the ascorbic acid coloring inhibition confirmation test of the compositions of the examples and comparative examples are shown in Tables 1 and 2.

[0199] Table 1

[0200]

[0201] [Table 2]

[0202]

[0203] The compositions of the examples had a coloring inhibition effect even when stored at a high temperature and showed excellent stability for a long time. On the other hand, coloring was observed in the compositions of the comparative examples under the test storage conditions.

[0204] (Examples 2-1 to 2-2, Comparative Example 2-1)

[0205] External compositions of the examples and comparative examples having the compositions shown in Table 3 were prepared according to a conventional method. The ratio of Δb in the evaluation items is the ratio of the comparative values with the color difference value of the external composition of Example 2-1 as the reference (1). That is, the ratio of stability represents the ratio when the Δb value of Example 2-1 is taken as 1.

[0206] The results of the ascorbic acid coloring inhibition confirmation test and the ascorbic acid precipitation inhibition confirmation test of the compositions of the examples and comparative examples are shown together in Table 3.

[0207] [Table 3]

[0208]

[0209] That is, it was found that the compositions shown in the examples achieved both the inhibition of ascorbic acid precipitation and the inhibition of coloring of the composition.

[0210] (Examples 3-1 to 3-3, Comparative Examples 3-1 to 3-2)

[0211] External compositions of the examples and comparative examples having the compositions shown in Table 4 were prepared according to a conventional method.

[0212] The results of the ascorbic acid coloring inhibition confirmation test and the ascorbic acid precipitation inhibition confirmation test of the compositions of the examples and comparative examples are shown together in Table 4.

[0213] [Table 4]

[0214]

[0215] (Examples 4-1 to 4-3, Comparative Examples 4-1 to 4-2)

[0216] External compositions of the examples and comparative examples having the compositions shown in Table 5 were prepared according to a conventional method.

[0217] The results of the ascorbic acid coloring inhibition confirmation test and the ascorbic acid precipitation inhibition confirmation test of the compositions of the examples and comparative examples are shown together in Table 4. In the evaluation items, the ratio of Δb is the ratio of the comparative values with the color difference value of the external composition of Example 4-1 as the reference (1). That is, the ratio of stability represents the ratio when the Δb value of Example 4-1 is set to 1.

[0218] [Table 5]

[0219]

[0220] It can be seen that the composition shown in the examples achieves both the inhibition of the precipitation of ascorbic acid at low temperatures and the inhibition of the coloring of the composition. For example, when the concentration of ethoxydiglycol is 40% by mass or more, precipitation can be seen due to the low pH, especially at low temperatures. For formulations with a slightly increased pH, no precipitation is seen at low temperatures even when the concentration of ethoxydiglycol is high, but when it is 30% by mass or more, a high degree of coloring is clearly seen. Therefore, it is preferred that the content of ethoxydiglycol is less than 30% even when it is formulated.

[0221] Furthermore, the results of the ascorbic acid coloring inhibition confirmation test, the ascorbic acid precipitation inhibition confirmation test, and the percutaneous absorption test of the compositions of other examples and comparative examples are shown in Table 6. Among the evaluation items, the ratio of Δb takes the color difference value of the external composition of Example 5-1 as the reference (1), and the ratio of the comparative value is recorded. That is, the stability ratio represents the ratio when the Δb value of Example 5-1 is set to 1.

[0222] [Table 6]

[0223]

[0224] Comparing the compositions of the examples with those of the comparative examples, it can be seen that the precipitation of ascorbic acid can be inhibited even under low-temperature storage, and in addition, both properties of inhibiting the coloring of the composition during storage can be achieved. In addition, it can be seen that the percutaneous absorbability of the composition of the present invention is also excellent.

[0225] The results of the percutaneous absorbability of the compositions of Examples 5-1 to 5-2 and Comparative Examples 5-1 to 5-2 are shown in Figure 1 .

[0226] Next, external compositions having the compositions shown in Tables 7 to 9 are prepared according to a conventional method. Thereafter, these compositions are subjected to tests based on each test item.

[0227] [Ascorbic acid coloring inhibition confirmation test]

[0228] The presence or absence of inhibition of coloring after storage at 40 °C or 50 °C of the external compositions having the compositions shown in Tables 7 to 9 is evaluated visually and using a color difference meter. Specifically, the confirmation test is carried out using the same method as that carried out in Examples 1 to 5 and Comparative Examples 1 to 5.

[0229] [Ascorbic acid precipitation inhibition confirmation test]

[0230] The presence or absence of ascorbic acid precipitation is evaluated visually when the external compositions having the compositions shown in Tables 7 to 9 are stored at low temperature. Specifically, the confirmation test is carried out using the same method as that carried out in Examples 1 to 5 and Comparative Examples 1 to 5.

[0231] [Transdermal Absorption Test of Ascorbic Acid]

[0232] The transdermal absorption of topical compositions based on several embodiments and comparative examples of the second invention was verified. By improving transdermal absorption, ascorbic acid penetrates into the muscle, thus expecting a higher anti-aging effect as a composition. That is, depending on the situation, the effect of ascorbic acid can be brought to the deep part of the stratum corneum.

[0233] The transdermal absorption of ascorbic acid in the topical compositions prepared in the examples and comparative examples was confirmed by using an evaluation based on the removal of the stratum corneum. Specifically, the confirmation test was carried out using the same method as that carried out in Examples 1 to 5 and Comparative Examples 1 to 5.

[0234] (Examples 6-1 to 8-1, Comparative Examples 6-2 to 8-3)

[0235] According to a conventional method, topical compositions of examples and comparative examples having the compositions shown in Table 7 were prepared. In the evaluation items in the same table, the ratio of Δb was based on the color difference value of the topical composition in Example 1 (1), and the ratio of the comparative value was recorded. That is, the ratio of stability represents the ratio of Δb. In addition, the ratio recorded in the column of the transdermal absorption test results of the topical compositions of the examples and comparative examples was a value obtained by ratio based on the transdermal absorption amount of Comparative Example 5-1 (formulation 40) in which 1,3-butanediol was incorporated into the matrix as 1.

[0236] Ratio = (Transdermal absorption amount of any composition in the example or comparative example (μg / cm 2 )) / (Transdermal absorption amount of the composition of Comparative Example 5-1 (μg / cm 2 ))

[0237] The results of each test of the compositions of the examples and comparative examples are shown together in Tables 7 to 9.

[0238] [Table 7]

[0239]

[0240] [Table 8]

[0241]

[0242] [Table 9]

[0243]

[0244] The compositions of the examples have a coloring inhibition effect even when stored at high temperatures, showing excellent stability over a long period. On the other hand, the compositions of the comparative examples showed coloring under the tested storage conditions. In addition, the compositions of the examples inhibited precipitation at low temperatures compared to the compositions of the comparative examples.

[0245] [Formulation Example]

[0246] The formulation examples are shown in Tables 10 to 12 below. All the formulation examples can be well applied to lotions, skin care liquids, etc. The contents in the formulation examples are all in mass %.

[0247]

[0248]

[0249]

Claims

1. An external composition containing: (A) At least one selected from ascorbic acid and salts of ascorbic acid, 10% by mass or less, (B) a diol having 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.

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