Carbonate aerosol topical skin preparation

Abstract

To provide a carbonated aerosol topical skin application that, even when applied to a thickened stratum corneum, such as xerosis, enables sufficient penetration of carbon dioxide gas into the stratum corneum.SOLUTION: Provided is a carbonated aerosol topical skin application consisting of an aerosol stock solution comprising the following components (A) to (C) and a propellant comprising component (D). Also provided is a carbon dioxide gas percutaneous permeation accelerator comprising the components (A) and (C). Further provided is a method for improving the percutaneous permeability of carbon dioxide gas in a composition comprising carbon dioxide gas by coexisting components (A) and (B) together with the carbon dioxide gas. (A) A stratum corneum water retention agent. (B) A water-soluble polymer (excluding one corresponding to component (A)). (C) Water. (D) Carbon dioxide gas.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a carbonated aerosol skin preparation for external use. [Background technology]

[0002] The skin plays a role in protecting the body from external stimuli, but with aging, a decrease in sebum secretion, a slower turnover rate, and dryness can lead to a skin condition called xerosis. Xerosis is characterized by a decrease in moisture content in the stratum corneum, resulting in pityriasis-like scales and shallow cracks, giving the skin an ichthyosis-like appearance. Furthermore, a decline in the skin's barrier function makes it more susceptible to the penetration of environmental allergens, which can lead to eczema-like lesions in winter and severe itching.

[0003] On the other hand, carbon dioxide gas is known to have blood circulation-promoting and warming effects, and skin cosmetics utilizing carbon dioxide gas are in use. For example, Patent Document 1 discloses an aerosol cosmetic that uses carbon dioxide gas as a propellant and contains solid fat, powder of a specific particle size, and a nonionic surfactant, and has excellent skin penetration. Furthermore, Patent Document 2 discloses that a carbon dioxide-containing viscous composition containing a thickener and carbon dioxide bubbles obtained by reacting an acid with a carbonate is effective for itching that is ineffective with antihistamines, antiallergic agents, nonsteroidal anti-inflammatory agents, and steroids, and has anti-inflammatory effects, wound healing-promoting effects, and transdermal absorption-promoting effects. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2018-43932 [Patent Document 2] International Publication No. 99 / 24043 Summary of the Invention [Problem to be solved by the invention]

[0005] Therefore, the present inventors have conducted research to provide an external skin preparation that can improve the disrupted turnover in dry skin problems such as xerosis and heal skin damage such as cracks by utilizing the blood circulation promoting effect and wound healing promoting effect of carbon dioxide gas. As a result, it has been found that the technology described in Patent Document 2 has the problem of strong irritation to the affected area due to the high salt concentration. Therefore, further research has been conducted on how to deliver high concentrations of carbon dioxide to the affected area using an aerosol composition in which carbon dioxide gas not derived from carbonate is dissolved at a high concentration, as in Patent Document 1.

[0006] However, it has been found that while aerosol skin preparations for topical use that use carbon dioxide gas as a propellant allow carbon dioxide gas to sufficiently penetrate healthy skin, carbon dioxide does not sufficiently penetrate areas where the stratum corneum has dried and thickened due to xerosis, etc., and is unable to reach the interior. Therefore, the present invention relates to a carbon dioxide aerosol skin preparation for topical use that allows carbon dioxide gas to sufficiently penetrate even when applied to a thickened stratum corneum due to xerosis, etc., and that can alleviate the symptoms of dry skin problems such as xerosis by promoting blood circulation, etc.

[0007] The present inventors have found that the above-mentioned problems can be solved by using carbon dioxide gas as a propellant and adding a stratum corneum humectant and a water-soluble polymer to the concentrate.

[0008] The present invention provides a carbonated aerosol skin preparation for external use, which comprises an aerosol concentrate containing the following components (A) to (C) and a propellant containing component (D). (A) Stratum corneum moisturizer (B) Water-soluble polymers (excluding those that fall under component (A)) (C) Water (D) Carbon dioxide

[0009] The present invention also provides a carbon dioxide gas percutaneous penetration enhancer containing the following components (A) and (C): (A) Stratum corneum moisturizer (C) Water

[0010] The present invention also provides a method for improving the transdermal permeability of carbon dioxide gas in a composition containing carbon dioxide gas, which comprises causing the following components (A) and (C) to coexist with carbon dioxide gas. (A) Stratum corneum moisturizer (C) Water

[0011] The present invention also provides a blood circulation promoter containing the following components (A), (C) and (D): (A) Stratum corneum moisturizer (C) Water (D) Carbon dioxide [Effects of the Invention]

[0012] The carbon dioxide aerosol skin preparation for external use of the present invention can allow carbon dioxide gas to penetrate sufficiently even when applied to a thickened stratum corneum such as that caused by xeroderma. DETAILED DESCRIPTION OF THE INVENTION

[0013] Aerosol concentrate The aerosol concentrate of the carbonated aerosol skin preparation for external use of the present invention contains the following components (A) to (C).

[0014] [Ingredient (A): stratum corneum moisturizer] Component (A) stratum corneum humectants are components that can increase the water retention capacity of the stratum corneum, and examples thereof include (A1) natural moisturizing factors, (A2) stratum corneum intercellular lipids, and (A3) mucopolysaccharides or derivatives thereof.

[0015] (Ingredient (A1): Natural moisturizing factor) Examples of the natural moisturizing factor of component (A1) include amino acids such as glycine and alanine, urea, lactic acid, and pyrrolidonecarboxylic acid, with urea being preferred.

[0016] From the viewpoints of improving carbon dioxide gas permeability, moisturizing properties, and skin irritation, the content of component (A1) in the aerosol concentrate is preferably 0.1% by mass or more, more preferably 1% by mass or more, even more preferably 3% by mass or more, even more preferably 4% by mass or more, and even more preferably 5% by mass or more, and is preferably 30% by mass or less, more preferably 25% by mass or less, and even more preferably 20% by mass or less. The specific range of the content of component (A1) in the aerosol concentrate is preferably 0.1 to 30% by mass, more preferably 1 to 25% by mass, even more preferably 3 to 25% by mass, even more preferably 4 to 20% by mass, and even more preferably 5 to 20% by mass.

[0017] (Component (A2): stratum corneum intercellular lipids) Examples of the intercellular lipids of component (A2) include triglycerides, wax esters, free fatty acids, squalene, and ceramide lipids, with ceramide lipids being particularly preferred.

[0018] The ceramide lipid may be either a natural ceramide or a pseudo-ceramide, and preferably contains one or more types selected from those represented by the following general formula (1) or (2).

[0019] Natural ceramides are represented by the general formula (1) and may be naturally occurring ceramides or synthetic products with the same structure.

[0020] [ka]

[0021] [In the formula, R 1 represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 7 to 19 carbon atoms which may be substituted with a hydroxyl group; Z 1 represents a methylene group or a methine group; X 1 , X 2 , and X 3 each independently represents a hydrogen atom, a hydroxyl group, or an acetoxy group; X 4 represents a hydrogen atom or forms an oxo group together with the adjacent oxygen atom (provided that Z1 When is a methine group, X 1 and X 2 One of the X's is a hydrogen atom, and the other is absent. 4 When forms an oxo group, X 3 does not exist. );R 2 represents a hydroxymethyl group or an acetoxymethyl group; R 3 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R 4 indicates a linear, branched, or cyclic saturated or unsaturated hydrocarbon group having 5 to 30 carbon atoms which may be substituted with a hydroxyl group, or a linear or branched, saturated or unsaturated fatty acid having 8 to 22 carbon atoms which may be substituted with a hydroxyl group which is ester-bonded to the ω-terminus of the alkyl group; the dashed line indicates that the bond may be unsaturated.]

[0022] In the general formula (1), preferably, R 1 is a linear alkyl group having 7 to 19 carbon atoms, more preferably 13 to 15 carbon atoms; R 4 is a linear alkyl group having 9 to 27 carbon atoms which may be substituted with a hydroxyl group, or a linear alkyl group having 9 to 27 carbon atoms to which linoleic acid is ester-bonded. 4 preferably represents a hydrogen atom or forms an oxo group together with an oxygen atom. 4 Preferred examples of the alkyl group include tricosyl, 1-hydroxypentadecyl, 1-hydroxytricosyl, heptadecyl, 1-hydroxyundecyl, and nonacosyl groups in which linoleic acid is ester-bonded at the ω-position.

[0023] The natural ceramide is preferably one or more selected from ceramide Types 1 to 7, in which sphingosine, dihydrosphingosine, phytosphingosine, or sphingadienine is amidated (e.g., porcine and human ceramides described in Figure 2 of J. Lipid Res., 24:759 (1983) and Figure 4 of J. Lipid. Res., 35:2069 (1994)). Furthermore, N-alkylated forms (e.g., N-methylated forms) of these ceramides are also included.

[0024] These natural ceramides may be optically active natural (D(-) form), optically active non-natural (L(+) form), or a mixture of natural and non-natural forms. The relative configuration of the above compounds may be that of the natural form, or may be any other non-natural configuration, or may be a mixture of these. Among these, one or more compounds selected from the group consisting of CERAMIDE 1, CERAMIDE 2, CERAMIDE 3, CERAMIDE 5, and CERAMIDE 6II (all listed in INCI, 8th Edition) and compounds represented by the following formula are preferred:

[0025] [ka]

[0026] These may be either natural extracts or synthetic products, and commercially available products can be used. When using commercially available natural ceramides, it is preferable to use one or more selected from Ceramide I, Ceramide III, Ceramide IIIA, Ceramide IIIB, Ceramide IIIC, and Ceramide VI (all from Cosmopharm), Ceramide TIC-001 (Takasago International), CERAMIDE II (Quest International), DS-Ceramide VI, DS-CLA-Phytoceramide, C6-Phytoceramide, DS-ceramide Y3S (DOOSAN), and CERAMIDE 2 (Sederma).

[0027] [ka]

[0028] The pseudo-ceramide is represented by the general formula (2).

[0029] [ka]

[0030] [In the formula, R 5 represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 10 to 22 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom; X 5 represents a hydrogen atom, an acetyl group, or a glyceryl group; R 6 represents a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 5 to 22 carbon atoms which may be substituted with a hydroxyl group or an amino group, or a hydrocarbon group having a linear or branched, saturated or unsaturated fatty acid having 8 to 22 carbon atoms which may be substituted with a hydroxyl group ester-bonded to the ω-terminus of the hydrocarbon group; R 7 represents a hydrogen atom or an alkyl group having a total of 1 to 30 carbon atoms which may be substituted with a hydroxyl group, a hydroxyalkoxy group, an alkoxy group, or an acetoxy group.

[0031] R 6 Particularly preferred are nonyl, tridecyl, pentadecyl, an undecyl group having linoleic acid ester-bonded at the ω-position, a pentadecyl group having linoleic acid ester-bonded at the ω-position, a pentadecyl group having 12-hydroxystearic acid ester-bonded at the ω-position, and an undecyl group having methyl-branched isostearic acid amide-bonded at the ω-position.

[0032] R 7 is R 5 When R is a hydrogen atom, it is an alkyl group having a total of 10 to 30 carbon atoms, preferably 12 to 20 carbon atoms, which may be substituted with a hydroxyl group, a hydroxyalkoxy group, an alkoxy group, or an acetoxy group, and R 5 When R is a linear, branched or cyclic saturated or unsaturated hydrocarbon group having 10 to 22 carbon atoms which may be substituted with a hydroxyl group, it is preferably a hydrogen atom or an alkyl group having a total of 1 to 8 carbon atoms which may be substituted with a hydroxyl group, a hydroxyalkoxy group, an alkoxy group or an acetoxy group. 7 The hydroxyalkoxy group or alkoxy group preferably has 1 to 7 carbon atoms.

[0033] The pseudo-ceramide represented by the general formula (2) includes a compound represented by the following formula:5 is a hexadecyl group, X 5 is a hydrogen atom, R 6 is a pentadecyl group, R 7 is a hydroxyethyl group (i.e., N-(hexadecyloxyhydroxypropyl)-N-hydroxyethylhexadecanamide); R 5 is a hexadecyl group, X 5 is a hydrogen atom, R 6 is a nonyl group, R 7 is a hydroxyethyl group (that is, N-(hexadecyloxyhydroxypropyl)-N-hydroxyethyldecanamide), and among these, the former is more preferred.

[0034] [ka]

[0035] From the viewpoint of improving carbon dioxide gas permeability, moisture retention, and emulsion stability, the content of component (A2) in the aerosol concentrate is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, and even more preferably 0.1% by mass or more, and is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 7.5% by mass or less, and even more preferably 5% by mass or less. The specific range of the content of component (A2) in the aerosol concentrate is preferably 0.001 to 15% by mass, more preferably 0.005 to 10% by mass, even more preferably 0.01 to 7.5% by mass, and even more preferably 0.1 to 5% by mass.

[0036] (Component (A3): mucopolysaccharide or its derivative) Examples of mucopolysaccharides or derivatives thereof as component (A3) include hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, keratan sulfate, heparin, heparinoids, carboxymethylchitin, etc. Furthermore, preferred examples of mucopolysaccharide salts include alkali metal salts such as lithium salts, sodium salts, and potassium salts; alkaline earth metal salts such as magnesium salts and calcium salts; ammonium salts; alkanolamine salts such as triethanolamine salts and diisopropanolamine salts; and basic amino acid salts such as lysine salts, arginine salts, and histidine salts. These can be used alone or in combination of two or more. Among these, heparinoids are preferred.

[0037] Heparinoids, also known as mucopolysaccharide polysulfates or heparinoids, are polysulfated mucopolysaccharides whose repeating units are disaccharides consisting of D-glucuronic acid and N-acetyl-D-galactosamine. Heparinoids listed in the Japanese Pharmacopoeia Non-Drug Standards 2002 are preferred.

[0038] The average molecular weight of the heparinoid is not particularly limited, but from the viewpoint of medicinal efficacy such as moisturizing effect, it is preferably 1,000 to 1,000,000 Mw, and more preferably 5,000 to 100,000 Mw. The amount (%) of organic sulfate groups in the heparinoid is not particularly limited, but from the viewpoint of medicinal efficacy such as moisturizing effect, it is preferably 20 to 40%, and more preferably 25 to 38%. The amount of organic sulfate groups is measured by the method described in the section on "Heparinoids" in the Japanese Pharmacopoeia 2002.

[0039] From the viewpoints of improving carbon dioxide gas permeability and moisturizing properties, the content of component (A3) in the aerosol concentrate is preferably 0.05% by mass or more, more preferably 0.07% by mass or more, even more preferably 0.1% by mass or more, and is preferably 1.5% by mass or less, more preferably 1.0% by mass or less, even more preferably 0.5% by mass or less, and even more preferably 0.4% by mass or less. The specific range of the content of component (A3) in the aerosol concentrate is preferably 0.05 to 1.5% by mass, more preferably 0.07 to 1.0% by mass, even more preferably 0.1 to 0.5% by mass, and even more preferably 0.1 to 0.4% by mass.

[0040] Component (A) is preferably one or more selected from components (A1) to (A3). When two or more of (A1) to (A3) are used as component (A), the content of each is as described above.

[0041] [Component (B): Water-soluble polymer] The water-soluble polymer of component (B) is not limited to those commonly used in topical skin preparations, and examples thereof include plant-derived polymers, microbial polymers, cellulose-derived polymers, starch-derived polymers, vinyl-based polymers, acrylic polymers, and polyoxyethylene-based polymers. However, water-soluble polymers that fall under component (A) are excluded from component (B). The weight-average molecular weight of the water-soluble polymer of component (B) is preferably 10,000 or more. The weight-average molecular weight is measured using a gel permeation chromatography (GPC)-multiangle laser light scattering (MALLS) system with polyethylene oxide as the standard.

[0042] The viscosity of a 2% by mass aqueous solution of component (B) at 20°C is preferably 5 mPa·s or more, more preferably 10 mPa·s or more, and even more preferably 20 mPa·s or more, from the viewpoint of retaining carbon dioxide gas in the agent after ejection and improving its permeability into the skin, and is preferably 100,000 mPa·s or less, more preferably 8,000 mPa·s or less, and even more preferably 5,000 mPa·s or less, from the viewpoint of improving ejection properties. The viscosity was measured at 20°C using a B-type viscometer (for example, VISCOMETER TVB-10, manufactured by Toki Sangyo Co., Ltd.).

[0043] Examples of plant-based polymers include gum arabic, locust bean gum, guar gum, karaya gum, carrageenan, pectin, agar, and starch (rice, corn, potato, wheat), while examples of microbial polymers include xanthan gum and gellan gum. Examples of cellulose-based polymers include methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, nitrocellulose, sodium cellulose sulfate, sodium carboxymethylcellulose, hydroxypropylmethylcellulose stearoxy ether, crystalline cellulose, cellulose powder, hydroxyethylcellulose hydroxypropylstearylether, sodium hydroxypropylsulfonate, and the like. Examples of starch-based polymers include carboxymethylstarch and methylhydroxypropylstarch. Examples of vinyl-based polymers include polyvinylmethylether, polyvinylpyrrolidone, and carboxyvinyl polymer. Examples of acrylic polymers include sodium polyacrylate, polyethyl acrylate, polyacrylic acid amide, acrylic acid / (meth)acrylate alkyl copolymer, (sodium acrylate / sodium acryloyldimethyltaurate) copolymer, polyacrylate crosspolymer-6, 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer, etc. Examples of polyoxyethylene polymers include polyethylene oxide, polyoxyethylene-polyoxypropylene copolymer, etc.

[0044] Of these, from the viewpoint of retaining carbon dioxide in the agent after ejection, improving its permeability into the skin, and reducing friction during application, water-soluble polymers having a sugar skeleton, such as plant-based polymers, microbial-based polymers, cellulose-based polymers, and starch-based polymers, are desirable, with cellulose-based polymers being more preferred, and hydroxypropyl methylcellulose, hydroxypropyl methylcellulose stearoxy ether, and hydroxyethyl cellulose being even more preferred.

[0045] From the viewpoint of retaining carbon dioxide gas in the agent after ejection and improving skin permeability, the content of component (B) in the aerosol concentrate is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, even more preferably 0.10% by mass or more, and is preferably 2.0% by mass or less, more preferably 1.0% by mass or less, even more preferably 0.50% by mass or less. The specific range of the content of component (B) in the aerosol concentrate is preferably 0.001 to 2.0% by mass, more preferably 0.005 to 2.0% by mass, even more preferably 0.01 to 1.0% by mass, even more preferably 0.10 to 0.50% by mass.

[0046] The mass ratio (A) / (B) of component (A) to component (B) in the aerosol concentrate is preferably within the ranges shown below for each type of component (A) from the viewpoint of increasing the permeability of carbon dioxide gas.

[0047] The mass ratio (A1) / (B) of the natural moisturizing factor of component (A1) to component (B) in the aerosol concentrate is preferably 0.25 or more, more preferably 0.5 or more, even more preferably 2.5 or more, and is preferably 30,000 or less, more preferably 2,000 or less, even more preferably 200 or less. The specific range of the mass ratio (A1) / (B) of the natural moisturizing factor of component (A1) to component (B) in the aerosol concentrate is preferably 0.25 to 30,000, more preferably 0.5 to 2,000, even more preferably 2.5 to 200.

[0048] The mass ratio (A2) / (B) of the intercellular lipids of component (A2) to component (B) in the aerosol concentrate is preferably 0.0005 or more, more preferably 0.01 or more, even more preferably 0.1 or more, and is preferably 15,000 or less, more preferably 1,000 or less, even more preferably 50 or less. The specific range of the mass ratio (A2) / (B) of the intercellular lipids of component (A2) to component (B) in the aerosol concentrate is preferably 0.0005 to 15,000, more preferably 0.01 to 1,000, even more preferably 0.1 to 50.

[0049] The mass ratio (A3) / (B) of the mucopolysaccharide or derivative thereof of component (A3) to component (B) in the aerosol concentrate is preferably 0.025 or more, more preferably 0.07 or more, even more preferably 0.2 or more, and is preferably 600 or less, more preferably 100 or less, even more preferably 5 or less. The specific range of the mass ratio (A3) / (B) of the mucopolysaccharide or derivative thereof of component (A3) to component (B) in the aerosol concentrate is preferably 0.025 to 600, more preferably 0.07 to 100, even more preferably 0.2 to 5.

[0050] [Component (C): Water] From the viewpoint of carbon dioxide gas permeability, the content of water (component (C)) in the aerosol concentrate is preferably 10% by mass or more, more preferably 20% by mass or more, even more preferably 40% by mass or more, and is preferably 90% by mass or less, more preferably 85% by mass or less, even more preferably 80% by mass or less. The specific range of the content of component (C) in the aerosol concentrate is preferably 10 to 90% by mass, more preferably 20 to 85% by mass, even more preferably 40 to 80% by mass.

[0051] [Ingredient (E): Glycyrrhetinic acid and its salts, glycyrrhizinic acid and its salts] The aerosol concentrate preferably further contains, as component (E), one or more selected from glycyrrhetic acid and its salts, and glycyrrhizinic acid and its salts, such as glycyrrhizinic acid and dipotassium glycyrrhizinate. From the viewpoint of suppressing inflammation in the target skin and supporting the effect of component (A), the content of component (E) in the aerosol concentrate is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, even more preferably 0.1% by mass or more, and is preferably 2.0% by mass or less, more preferably 1.5% by mass or less, even more preferably 1.0% by mass or less.

[0052] From the viewpoint of supporting the effect of component (A) and enhancing the transdermal permeability of carbon dioxide gas, the mass ratio (E) / (B) of component (E) to component (B) in the aerosol concentrate is preferably 0.005 or more, more preferably 0.05 or more, even more preferably 0.2 or more, and is preferably 2000 or less, more preferably 300 or less, even more preferably 100 or less. The specific range of the mass ratio (E) / (B) of component (E) to component (B) in the aerosol concentrate is preferably 0.005 to 2000, more preferably 0.05 to 300, even more preferably 0.2 to 100.

[0053] [Other optional ingredients] The aerosol concentrate may contain other ingredients commonly used in topical skin preparations in addition to the above-mentioned ingredients. Examples of such ingredients include oils that are liquid at 25°C, polyhydric alcohols, pH adjusters, thickeners, preservatives, powders, ethanol, antioxidants, colorants, fragrances, moisturizers, blood circulation promoters, cooling agents, antiperspirants, disinfectants, whitening agents, anti-inflammatory agents, and skin activators. These ingredients are not limited to their individual uses, but can also be diverted to other uses or used in combination with other uses depending on the intended purpose. For example, an antiperspirant may be used as a fragrance, or a combination of an antiperspirant and a fragrance may be used.

[0054] The polyhydric alcohol may be any one that is commonly used in cosmetics, and examples thereof include dihydric polyhydric alcohols such as ethylene glycol, propylene glycol, propanediol, 1,3-butylene glycol, 1,3-propanediol, dipropylene glycol, polyethylene glycol, and polypropylene glycol; and trihydric or higher polyhydric alcohols such as glycerin and sorbitol.

[0055] From the viewpoint of improving the penetration feeling of the ejected agent into the skin and improving uniform application, the content of the polyhydric alcohol in the aerosol concentrate is preferably 1% by mass or more, more preferably 2% by mass or more, even more preferably 5% by mass or more, even more preferably 10% by mass or more, and is preferably 50% by mass or less, more preferably 40% by mass or less, even more preferably 30% by mass or less, even more preferably 20% by mass or less. The specific range of the content of the polyhydric alcohol in the aerosol concentrate is preferably 1 to 50% by mass, more preferably 2 to 40% by mass, even more preferably 5 to 30% by mass, even more preferably 10 to 20% by mass.

[0056] Examples of pH adjusters include one or more selected from the group consisting of organic acids, organic acid salts, amino acids, amino acid salts, amines, inorganic acids, inorganic acid salts, and inorganic bases. Examples of organic acids include glycolic acid, citric acid, malic acid, succinic acid, tartaric acid, and lactic acid, and examples of their salts include potassium salts and sodium salts. Examples of amino acids include glutamic acid, aspartic acid, arginine, and lysine, and examples of their salts include sodium salts, hydrochlorides, and succinates. Examples of amines include aliphatic amines such as monoethanolamine, triethanolamine, methylamine, ethylamine, trimethylamine, triethylamine, ethylenediamine, and tetramethylethylenediamine. Examples of inorganic acids include phosphoric acid, and examples of inorganic acid salts include potassium dihydrogen phosphate and disodium hydrogen phosphate. Examples of inorganic bases include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide.

[0057] Propellant [Component (D): Carbon dioxide] In the present invention, carbon dioxide gas (component (D)) is used as a propellant. Other propellants can be used in combination with carbon dioxide gas. Examples of propellants other than carbon dioxide gas include liquefied petroleum gas (ethane, propane, ethylene, isobutane, normal butane, propylene, and mixtures thereof (e.g., mixtures of isobutane and propane, or propane and butane)), ether-based propellants (dimethyl ether, etc.), fluorocarbons (fluorocarbons, chlorofluorocarbons, bromochlorofluorocarbons, etc.), compressed gases (nitrogen, air, mixtures thereof, etc.), and chlorofluorocarbons (monochlorodifluoroethane, tetrafluoroethane, etc.). Of these, nitrogen, dimethyl ether, and liquefied petroleum gas are preferred. When other propellants are used in combination with carbon dioxide gas (component (D)), any of these can be used alone or in combinations of two or more.

[0058] When a propellant other than carbon dioxide gas of component (D) is used in combination as a propellant, in order not to impair the effect of carbon dioxide gas, the proportion of carbon dioxide gas of component (D) in the total propellant is preferably 20% or more, more preferably 40% or more, even more preferably 60% or more, and even more preferably 80% or more, based on the volume of the gaseous state (1013.25 hPa, 25°C).

[0059] Carbonated aerosol skin topical agent The carbonated aerosol skin preparation of the present invention can be produced by preparing an aerosol concentrate containing components (A) to (C) and filling it into a pressure-resistant container together with a propellant containing component (D). The spray form is preferably a foam type, in which the aerosol is discharged in the form of a foam.

[0060] The ratio of (D) carbon dioxide gas to 100 parts by mass of the aerosol concentrate is, from the viewpoint of improving the solubility of carbon dioxide gas in the aerosol concentrate, foam viscosity, and sprayability, preferably 0.01 parts by mass or more, more preferably 0.10 parts by mass or more, even more preferably 0.125 parts by mass or more, even more preferably 0.25 parts by mass or more, even more preferably 0.5 parts by mass or more, and even more preferably 1.0 part by mass or more, and is preferably 5.0 parts by mass or less, more preferably 3.0 parts by mass or less.

[0061] The pH of the carbonated aerosol skin preparation for external use of the present invention immediately after ejection is preferably 4.0 or higher, more preferably 4.5 or higher, and even more preferably 5.0 or higher, from the viewpoint of suppressing skin irritation, and is preferably 7.0 or lower, more preferably 6.5 or lower, and even more preferably 6.0 or lower, from the viewpoint of increasing the carbon dioxide gas concentration. In the present invention, the pH immediately after ejection refers to the pH measured 1 minute after ejection from the aerosol container in an environment of 25°C.

[0062] When the carbon dioxide aerosol topical skin preparation of the present invention is a foam type, the viscosity of the discharged foam is preferably 0.1 Pa·s or more, more preferably 0.5 Pa·s or more, even more preferably 1.0 Pa·s or more, and is preferably 50 Pa·s or less, more preferably 40 Pa·s or less, even more preferably 30 Pa·s or less, from the viewpoint of retaining carbon dioxide gas in the preparation after discharge and improving its permeability into the skin. Here, the viscosity of the discharged foam is measured using a B-type viscometer (e.g., VISCOMETER TVB-10, manufactured by Toki Sangyo Co., Ltd.) under the conditions of rotor No. 3, 12 rpm, 25°C, and 10 seconds.

[0063] Carbon dioxide percutaneous penetration enhancer, method for improving carbon dioxide percutaneous penetration, and blood circulation enhancer The carbon dioxide transdermal penetration enhancer of the present invention contains the above-mentioned components (A) and (C), and when used in combination with carbon dioxide, can enhance the transdermal penetration of carbon dioxide. Specific examples and contents of components (A) and (C) and optional components in the carbon dioxide transdermal penetration enhancer of the present invention are the same as those for the aerosol concentrate described above.

[0064] Furthermore, by allowing the above-mentioned components (A) and (C) to coexist with carbon dioxide, the transdermal permeability of the carbon dioxide-containing composition can be improved, and carbon dioxide can be sufficiently penetrated even when applied to a thickened stratum corneum such as that caused by xerosis. The improved transdermal permeability of carbon dioxide can promote blood circulation.

[0065] The blood circulation promoter of the present invention contains the above-mentioned components (A), (C) and (D), and has excellent transdermal permeability of carbon dioxide gas, thereby promoting blood circulation. Specific examples and contents of components (A), (C), and (D) and optional components in the blood circulation promoter of the present invention are the same as those for the aerosol concentrate described above.

[0066] [How to use] The carbonic acid aerosol skin preparation of the present invention is applied in an appropriate amount to the skin, particularly to the skin of the entire body excluding the scalp, preferably to the face, body, limbs, etc., more preferably to the skin of the hands and feet. It may be taken in the hands and spread over the target area, or it may be ejected directly onto the target area. In the case of a foam type, it is preferable to take it in the hands and apply it without crushing the foam. It is particularly preferable to apply it to areas with thick stratum corneum that are prone to dryness, such as the hands, feet, their fingers, heels, elbows, and knees. The amount to be applied is preferably about 1 g for both hands.

[0067] With respect to the above-described embodiment, further preferred aspects of the present invention will be disclosed below.

[0068] <1> A carbonated aerosol skin preparation for topical use, comprising an aerosol concentrate containing the following ingredients (A) to (C) and a propellant containing ingredient (D). (A) Stratum corneum moisturizer (B) Water-soluble polymers (excluding those that fall under component (A)) (C) Water (D) Carbon dioxide

[0069] <2> Component (A) is preferably one or more selected from (A1) natural moisturizing factors, (A2) stratum corneum intercellular lipids, and (A3) mucopolysaccharides and derivatives thereof. <1> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0070] <3> The component (A1) is preferably at least one selected from amino acids, urea, lactic acid, and pyrrolidone carboxylic acid, more preferably urea. <2> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0071] <4> The content of component (A1) in the aerosol concentrate is preferably 0.1% by mass or more, more preferably 1% by mass or more, even more preferably 3% by mass or more, even more preferably 4% by mass or more, even more preferably 5% by mass or more, and is preferably 30% by mass or less, more preferably 25% by mass or less, even more preferably 20% by mass or less. <2> or <3> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0072] <5> Component (A2) is preferably one or more selected from triglycerides, wax esters, free fatty acids, squalene, and ceramide lipids, more preferably ceramide lipids. <2> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0073] <6> The content of component (A2) in the aerosol concentrate is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, and even more preferably 0.1% by mass or more, and is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 7.5% by mass or less, and even more preferably 5% by mass or less. <2> or <5> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0074] <7> Component (A3) is preferably one or more selected from hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, keratan sulfate, heparin, heparinoids, and carboxymethylchitin, more preferably a heparinoid. <2> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0075] <8> The content of component (A3) in the aerosol concentrate is preferably 0.05% by mass or more, more preferably 0.07% by mass or more, even more preferably 0.1% by mass or more, and is preferably 1.5% by mass or less, more preferably 1.0% by mass or less, even more preferably 0.5% by mass or less, and even more preferably 0.4% by mass or less. <2> or <7> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0076] <9> Component (B) is preferably at least one selected from plant-based polymers, microbial-based polymers, cellulose-based polymers, starch-based polymers, vinyl-based polymers, acrylic-based polymers, and polyoxyethylene-based polymers, more preferably at least one selected from water-soluble polymers having a sugar skeleton, even more preferably at least one selected from cellulose-based polymers, and even more preferably at least one selected from hydroxypropyl methylcellulose, hydroxypropyl methylcellulose stearoxy ether, and hydroxyethyl cellulose. <1> ~ <8> 10. The carbonated aerosol topical skin preparation according to claim 1, wherein the

[0077] <10> The viscosity of a 2% by mass aqueous solution of component (B) at 20°C is preferably 5 mPa·s or more, more preferably 10 mPa·s or more, even more preferably 20 mPa·s or more, and is preferably 100,000 mPa·s or less, more preferably 8,000 mPa·s or less, even more preferably 5,000 mPa·s or less. <1> ~ <9> 10. The carbonated aerosol topical skin preparation according to claim 1, wherein the

[0078] <11> The content of component (B) in the aerosol concentrate is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, even more preferably 0.10% by mass or more, and is preferably 2.0% by mass or less, more preferably 1.0% by mass or less, even more preferably 0.50% by mass or less. <1> ~ <10> 10. The carbonated aerosol topical skin preparation according to claim 1, wherein the

[0079] <12> The mass ratio (A1) / (B) of component (A1) to component (B) in the aerosol concentrate is preferably 0.25 or more, more preferably 0.5 or more, even more preferably 2.5 or more, and is preferably 30,000 or less, more preferably 2,000 or less, even more preferably 200 or less. <2> , <3> , <4> , <9> , <10> or <11> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0080] <13> The mass ratio (A2) / (B) of component (A2) to component (B) in the aerosol concentrate is preferably 0.0005 or more, more preferably 0.01 or more, even more preferably 0.1 or more, and is preferably 15,000 or less, more preferably 1,000 or less, even more preferably 50 or less. <2> , <5> , <6> , <9> , <10> or <11> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0081] <14> The mass ratio (A3) / (B) of component (A3) to component (B) in the aerosol concentrate is preferably 0.025 or more, more preferably 0.07 or more, even more preferably 0.2 or more, and is preferably 600 or less, more preferably 100 or less, even more preferably 5 or less. <2> , <7> , <8> , <9> , <10> or <11> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0082] <15> The content of component (C) in the aerosol concentrate is preferably 10% by mass or more, more preferably 20% by mass or more, even more preferably 40% by mass or more, and is preferably 90% by mass or less, more preferably 85% by mass or less, even more preferably 80% by mass or less. <1> ~ <14> 10. The carbonated aerosol topical skin preparation according to claim 1, wherein the

[0083] <16> Preferably, the aerosol concentrate further contains, as component (E), one or more selected from glycyrrhetic acid and its salts, and glycyrrhizinic acid and its salts. <1> ~ <15> 10. The carbonated aerosol topical skin preparation according to claim 1, wherein the

[0084] <17> The content of component (E) in the aerosol concentrate is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, even more preferably 0.1% by mass or more, and is preferably 2.0% by mass or less, more preferably 1.5% by mass or less, even more preferably 1.0% by mass or less. <16> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0085] <18> The mass ratio (E) / (B) of component (E) to component (B) in the aerosol concentrate is preferably 0.005 or more, more preferably 0.05 or more, even more preferably 0.2 or more, and is preferably 2000 or less, more preferably 300 or less, even more preferably 100 or less. <16> or <17> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0086] <19> Preferably, the aerosol concentrate further contains a polyhydric alcohol. <1> ~ <18> 10. The carbonated aerosol topical skin preparation according to claim 1, wherein the

[0087] <20> The polyhydric alcohol is preferably at least one selected from ethylene glycol, propylene glycol, propanediol, 1,3-butylene glycol, 1,3-propanediol, dipropylene glycol, polyethylene glycol, polypropylene glycol, glycerin, and sorbitol. <19> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0088] <21> The content of polyhydric alcohol in the aerosol concentrate is preferably 1% by mass or more, more preferably 2% by mass or more, even more preferably 5% by mass or more, even more preferably 10% by mass or more, and is preferably 50% by mass or less, more preferably 40% by mass or less, even more preferably 30% by mass or less, even more preferably 20% by mass or less. <19> or <20> 2. The carbonate aerosol skin topical preparation according to claim 1.

[0089] <22> The ratio of component (D) to 100 parts by mass of the aerosol concentrate is preferably 0.01 parts by mass or more, more preferably 0.10 parts by mass or more, even more preferably 0.125 parts by mass or more, even more preferably 0.25 parts by mass or more, even more preferably 0.5 parts by mass or more, even more preferably 1.0 parts by mass or more, and is preferably 5.0 parts by mass or less, more preferably 3.0 parts by mass or less. <1> ~ <21> 10. The carbonated aerosol topical skin preparation according to claim 1, wherein the

[0090] <23> The pH immediately after ejection is preferably 4.0 or higher, more preferably 4.5 or higher, and even more preferably 5.0 or higher, and is preferably 7.0 or lower, more preferably 6.5 or lower, and even more preferably 6.0 or lower. <1> ~ <22> 10. The carbonated aerosol topical skin preparation according to claim 1, wherein the

[0091] <24> Preferably, it is dispensed in foam form. <1> ~ <23> 10. The carbonated aerosol topical skin preparation according to claim 1, wherein the

[0092] <25> A carbon dioxide transdermal penetration enhancer containing the following ingredients (A) and (C). (A) Stratum corneum moisturizer (C) Water

[0093] <26> Preferably, the composition further contains the following component (B): <25> The carbon dioxide transdermal penetration enhancer according to claim 1. (B) Water-soluble polymers (excluding those that fall under component (A))

[0094] <27> A method for improving the transdermal permeability of carbon dioxide gas in a composition containing carbon dioxide gas, comprising allowing the following components (A) and (C) to coexist together with carbon dioxide gas. (A) Stratum corneum moisturizer (C) Water

[0095] <28> Preferably, the following component (B) is further present: <27> The method for promoting transdermal permeation of carbon dioxide gas according to claim 1. (B) Water-soluble polymers (excluding those that fall under component (A))

[0096] <29> A blood circulation promoter containing the following ingredients (A), (C) and (D). (A) Stratum corneum moisturizer (C) Water (D) Carbon dioxide [Example]

[0097] Examples 1 to 24, Comparative Examples 1 to 2 Aerosol concentrates were prepared according to the formulations shown in Tables 1 to 3 and filled into aluminum pressure containers together with a propellant (carbon dioxide gas or LPG) to produce aerosol skin cosmetics. These aerosol skin cosmetics were evaluated for their ability to retain carbon dioxide and the amount of moisture in the stratum corneum after repeated use according to the following methods and criteria.

[0098] <Carbon dioxide retention> Measurements were carried out using the following equipment and under the following conditions using the ATR-IR method. The IR spectrum of carbon dioxide gas is at 2350 cm -1 It is known that strong absorption occurs around this region, and the retention of carbon dioxide concentration in the preparation was evaluated based on the peak area ratio of the peak area 5 minutes after ejection to the peak area immediately after ejection, according to the following criteria. (Measurement conditions and equipment) Equipment: PerkinElmer SpectrumOne / Universal ATR unit Resolution: 16cm -1 Number of scans: 16 Atmospheric correction function: OFF Carbon dioxide retention (%) = (peak area after 5 minutes) / (peak area immediately after ejection) × 100 A: Over 90% B: 75% or more C: 50% or more D: 20% or more E: Less than 20%

[0099] <Changes in keratin moisture after repeated use> Five dry skin monitors had a 3x3cm marking made on their shins, and 0.05g of the formulation was applied once a day for 14 days. The moisture content of the stratum corneum was measured using a SKIKON-200EX (IBS) before and after 14 days of use to determine the change in moisture content after continued use (measurement conditions: 20°C, 40% RH), and the results were evaluated according to the following criteria. Change in stratum corneum moisture content (ΔμS) = (stratum corneum moisture content after 14 days of use) - (stratum corneum moisture content before use) A:100μS or more B:50μS or more C: 30μS or more D: Less than 10 μS

[0100] <Level of Skin Flushing Caused by Carbon Dioxide Gas (Examples 1, 2, 7, 18, Comparative Examples 1 and 2)> Five dry skin monitors had a 3x3cm marking made on their shins and had 0.05g of the formulation applied once a day for 14 days. After 14 days of application, 2g of the formulation was applied to the skin for 2 minutes, and the degree of flushing after wiping was evaluated according to the following criteria. A: Clearly flushed B: Slightly flushed C: Slightly flushed D: Almost no change

[0101] [Table 1]

[0102] [Table 2]

[0103] [Table 3]

[0104] *1:Metolose 90SH-15000 (Shin-Etsu Chemical Co., Ltd.) *2:Metolose 60SH-4000 (Shin-Etsu Chemical Co., Ltd.) *3: Sangelose 90L (manufactured by Daido Chemical Industry Co., Ltd.) *4:Natrosol 250HX PHARM (manufactured by Ashland) *5: Alcox E-100 (manufactured by Meisei Chemical Industry Co., Ltd.) *6: CMC Daicel 1150 (manufactured by Daicel Miraize) *7: Carbopol 980 (manufactured by Lubrizol Advanced Materials) *8: PEMULEN TR1 (manufactured by Lubrizol Advanced Materials) *9:Echo Gum T (manufactured by DSP Gokyo Food & Chemical Co., Ltd.) *10: Lipidure PMB (NOF Corporation) *11: Sphingolipid E ​​(Kao Corporation)

[0105] Formulation example (mass %; all active ingredients) (Undiluted) (A) N-(hexadecyloxypropyl)-N-hydroxyethylhexadecanamide (*11) 1 (B) Acrylic acid / C10-30 alkyl acrylate copolymer (*8) 0.1 Sodium N-stearoyl-N-methyl taurate (*12) 0.33 Glycerin 15 (C) Purified water remainder Total stock solution: 100 (Propellant) Carbon dioxide gas

[0106] Stock solution: (D) carbon dioxide = 100:2.2 *11: Sphingolipid E ​​(Kao Corporation) *8: PEMULEN TR1 (manufactured by Lubrizol Advanced Materials) *12: Nikkor SMT (manufactured by Nikko Chemicals)

Claims

1. A carbonated aerosol skin preparation for external use, comprising an aerosol concentrate containing the following components (A) to (C) and a propellant containing component (D): (A) Stratum corneum moisturizer (B) Water-soluble polymer (C) Water (D) Carbon dioxide The component (A) is the following component (A1), component (A2), and component (A3); (A1) Urea or amino acid 0.1% by mass or more and 20% by mass or less (A2) Ceramide lipid 0.1% by mass or more and 5% by mass or less (A3) Heparinoids or hyaluronic acid 0.07% by mass or more and 0.4% by mass or less Either Component (B) is hydroxypropyl methylcellulose or hydroxypropyl methylcellulose stearoxy ether, when the component (A) is (A1), the mass ratio of the component (A1) to the component (B), (A1) / (B), is 2.5 or more and 200 or less; when the component (A) is (A2), the mass ratio of the component (A2) to the component (B), (A2) / (B), is 0.1 or more and 50 or less; When the component (A) is (A3), the mass ratio of the component (A3) to the component (B), (A3) / (B), is 0.07 or more and 300 or less. Carbonate aerosol skin topical agent for improving dry skin symptoms.

2. 2. The carbonated aerosol skin preparation according to claim 1, wherein the content of component (B) in the aerosol concentrate is 0.001% by mass or more and 2.0% by mass or less.

3. 3. The carbonated aerosol skin preparation according to claim 1, further comprising, as component (E), one or more selected from glycyrrhetinic acid and its salts, and glycyrrhizinic acid and its salts.

4. The carbonated aerosol skin preparation for external use according to any one of claims 1 to 3, which is discharged in the form of foam.

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