Carbonated aerosol topical skin preparation

Abstract

To provide a carbonated aerosol topical skin application comprising a heparinoid in a stable manner and being less irritating to skin.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). The pH of the mixture of aerosol stock solution and propellant is 4.5 or more and 7.0 or less. (A) A heparinoid. (B) A pH regulator. (C) Water. (D) Carbon dioxide gas.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a carbonated aerosol skin external preparation.

Background Art

[0002] Heparin-like substances have many hydrophilic groups such as sulfate groups, carboxyl groups, and hydroxyl groups in their structures and have pharmacological effects such as a moisturizing effect and an anti-inflammatory effect. The efficacy and effects of skin external preparations containing heparin-like substances are for the treatment and prevention of thrombophlebitis (including hemorrhoids), pain and inflammatory diseases (induration and pain after injection) based on blood circulation disorders, frostbite, hypertrophic scars and keloids, progressive palmoplantar keratoderma, seborrheic dermatitis, swelling, hematoma, tenosynovitis, muscle pain, arthritis, and muscular torticollis (in infancy) after trauma (contusion, sprain, bruise). And as dosage forms of skin external preparations containing heparin-like substances, creams, soft ointments, lotions, and foam sprays are on the market.

[0003] Among these dosage forms, the foam spray is a dosage form that can prevent dripping of the liquid at the affected area compared to the lotion and is easier to spread on the affected area than creams and ointments. For example, in Patent Document 1, in view of the fact that liquefied natural gas shows irritation to the skin, a composition for a screen former containing a heparin-like substance, a nonionic surfactant, and a specific polyol that can form foam by a screen former without using a gas for foaming is described. On the other hand, Patent Document 2 describes a foaming composition comprising a heparin-like substance and a specific nonionic surfactant, and consisting of a stock solution containing no lower alcohol and a propellant.

[0004] On the other hand, it is known that carbon dioxide gas has a blood circulation promoting effect and a warming effect, and aerosol-type cosmetics using carbon dioxide gas as a propellant are used (for example, Patent Document 3).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

[0006] The composition for a screen former described in Cited Document 1 has difficulty in producing fine bubbles and is likely to feel friction during application. In addition, since the foaming composition described in Cited Document 2 uses LPG as a propellant, irritation to the skin becomes a problem. And, the pH of both formulations was adjusted near neutrality and tended to be higher than the pH of the skin, which is weakly acidic.

[0007] Therefore, the present inventors intensively studied to develop a carbonated aerosol topical skin preparation containing a heparin-like substance. However, it was found that a problem of the storage stability of the heparin-like substance occurred because the stable pH range of the heparin-like substance is near neutrality, while the mixed solution of the aerosol stock solution and carbon dioxide gas in the pressure-resistant container becomes acidic.

[0008] Accordingly, the present invention relates to a carbonated aerosol topical skin preparation in which a heparin-like substance is stably formulated and which causes less irritation to the skin. [Means for Solving the Problems]

[0009] The present inventors have found that the above problems can be solved by using carbon dioxide gas as a propellant, containing a pH adjuster together with a heparin-like substance in the stock solution, and setting the pH of the mixed solution with carbon dioxide gas to 4.5 or more and 7.0 or less.

[0010] The present invention provides a carbonated aerosol topical skin preparation comprising an aerosol stock solution containing the following components (A) to (C) and a propellant containing a component (D), wherein the pH of the mixed solution of the aerosol stock solution and the propellant is 4.5 or more and 7.0 or less. (A) Heparin analog (B) pH adjuster (C) Water (D) Carbon dioxide

Advantages of the Invention

[0011] The carbonated aerosol topical skin preparation of the present invention contains a heparin analog stably and causes less irritation to the skin.

Embodiments for Carrying Out the Invention

[0012] ● Aerosol stock solution The aerosol stock solution in the carbonated aerosol topical skin preparation of the present invention contains the following components (A) to (C).

[0013] 〔Component (A): Heparin analog〕 The heparin analog of component (A) is a substance also called mucopolysaccharide polysulfate ester or heparinoid, and is a polysulfated mucopolysaccharide having a disaccharide composed of D-glucuronic acid and N-acetyl-D-galactosamine as a repeating unit. As the heparin analog, the heparin analog described in the Japanese Pharmaceutical Excipients Standard 2002 is preferred.

[0014] The average molecular weight of the heparin analog is not particularly limited, but from the viewpoint of drug effects such as a moisturizing effect, 1000 to 1000000 Mw is preferred, and 5000 to 100000 Mw is particularly preferred. In addition, the amount (%) of the organic sulfate group in the heparin analog is not particularly limited, but from the viewpoint of drug effects such as a moisturizing effect, 20 to 40% is preferred, and 25 to 38% is more preferred. The amount of the organic sulfate group is measured by the method described in the section of "Heparin analog" in the Japanese Pharmaceutical Excipients Standard 2002.

[0015] The content of component (A) in the aerosol stock solution is preferably 0.05% by mass or more, more preferably 0.07% by mass or more, still more preferably 0.1% by mass or more, from the viewpoints of medicinal effects such as moisturizing effects and usability, etc. Also, it is preferably 0.6% by mass or less, more preferably 0.5% by mass or less, still more preferably 0.4% by mass or less. The specific range of the content of component (A) in the aerosol stock solution is preferably 0.05 - 0.6% by mass, more preferably 0.07 - 0.5% by mass, still more preferably 0.1 - 0.4% by mass.

[0016] [Component (B): pH adjuster] As the pH adjuster of component (B), one or more compounds 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 are preferable. Examples of organic acids include glycolic acid, citric acid, malic acid, succinic acid, tartaric acid, lactic acid, etc., and examples of their salts include potassium salts, sodium salts, etc. Examples of amino acids include glutamic acid, aspartic acid, arginine, lysine, etc., and examples of their salts include sodium salts, hydrochloride salts, succinate salts, etc. Examples of amines include aliphatic amines such as monoethanolamine, triethanolamine, methylamine, ethylamine, trimethylamine, triethylamine, ethylenediamine, tetramethylethylenediamine, etc. Examples of inorganic acids include phosphoric acid, and examples of inorganic acid salts include potassium dihydrogen phosphate, disodium hydrogen phosphate, etc. Examples of inorganic bases include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide, etc. Among these, from the viewpoint of enhancing the stability of heparin-like substances, organic acids, organic acid salts, amino acids, amino acid salts, amines, and inorganic bases are preferable.

[0017] The content of component (B) in the aerosol stock solution is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.15% by mass or more, and is preferably 1.0% by mass or less, more preferably 0.7% by mass or less, still more preferably 0.5% by mass or less. The specific range of the content of component (B) in the aerosol stock solution is preferably 0.05 to 1.0% by mass, more preferably 0.1 to 0.7% by mass, still more preferably 0.15 to 0.5% by mass.

[0018] From the viewpoint of the stability of the heparin-like substance, the mass ratio (A) / (B) of component (A) and component (B) in the aerosol stock solution is preferably 0.05 or more, more preferably 0.1 or more, still more preferably 0.2 or more, and is preferably 12 or less, more preferably 5 or less, still more preferably 2.5 or less. The specific range of the mass ratio (A) / (B) of component (A) and component (B) in the aerosol stock solution is preferably 0.05 to 12, more preferably 0.1 to 5, still more preferably 0.2 to 2.5.

[0019] [Component (C): Water] From the viewpoints of the penetration feeling of the discharged agent into the skin and the solubility of the heparin-like substance and other components, the water content of component (C) in the aerosol stock solution is preferably 10% by mass or more, more preferably 20% by mass or more, still more preferably 40% by mass or more, and is preferably 90% by mass or less, more preferably 85% by mass or less, still more preferably 80% by mass or less. The specific range of the content of component (C) in the aerosol stock solution is preferably 10 to 90% by mass, more preferably 20 to 85% by mass, still more preferably 40 to 80% by mass.

[0020] [Component (E): Water-soluble polymer] The aerosol stock solution can further contain a water-soluble polymer as component (E). The water-soluble polymer is not limited as long as it is used in ordinary external preparations for skin, and examples thereof include plant-based polymers, microbial polymers, mucopolysaccharides, cellulose-based polymers, starch-based polymers, vinyl-based polymers, acrylic-based polymers, polyoxyethylene-based polymers, and the like. The weight-average molecular weight of the water-soluble polymer of component (E) is preferably 10,000 or more. The weight-average molecular weight is measured by using a gel permeation chromatography (GPC)-multi-angle laser light scattering detector (MALLS) system with polyethylene oxide as a standard substance.

[0021] Examples of plant-based polymers include gum arabic, locust bean gum, guar gum, karaya gum, carrageenan, pectin, agar, starch (rice, corn, potato, wheat), etc. Examples of microbial polymers include xanthan gum, gellan gum, etc. Examples of mucopolysaccharides include hyaluronic acid, tuberose polysaccharide, jellyfish polysaccharide, etc. Examples of cellulose-based polymers include methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose stearoxy ether, nitrocellulose, sodium cellulose sulfate, sodium carboxymethyl cellulose, crystalline cellulose, cellulose powder, hydroxyethyl cellulose hydroxypropyl stearyl ether sodium hydroxypropyl sulfonate, etc. Examples of starch-based polymers include carboxymethyl starch, methyl hydroxypropyl starch, etc. Examples of vinyl polymers include polyvinyl methyl ether, polyvinyl pyrrolidone, carboxyvinyl polymer, etc. Examples of acrylic polymers include sodium polyacrylate, polyethyl acrylate, polyacrylamide, acrylic acid / (meth)acrylic acid alkyl copolymer, (sodium acrylate / sodium acryloyldimethyltaurine) copolymer, polyacrylate cross polymer-6, 2-methacryloyloxyethyl phosphorylcholine / butyl methacrylate copolymer, etc. Examples of polyoxyethylene polymers include polyethylene oxide, etc.

[0022] Among these, from the viewpoints of maintaining the agent after ejection in weakly acidic condition and reducing friction during application, water-soluble polymers having a sugar backbone such as plant-based polymers, microbial polymers, mucopolysaccharides, cellulose-based polymers, starch-based polymers, etc. are preferable, cellulose-based polymers are more preferable, and hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose stearoxy ether, and hydroxyethyl cellulose are even more preferable.

[0023] The content of component (E) in the aerosol stock solution is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, still more preferably 0.10% by mass or more, and even more preferably 0.20% by mass or more, from the viewpoints of maintaining the agent after discharge in a weakly acidic state and reducing friction during application. Also, it is preferably 5.0% by mass or less, more preferably 2.0% by mass or less, still more preferably 1.0% by mass or less, and even more preferably 0.80% by mass or less. The specific range of the content of component (E) in the aerosol stock solution is preferably 0.01 to 5.0% by mass, more preferably 0.05 to 2.0% by mass, still more preferably 0.10 to 1.0% by mass, and even more preferably 0.20 to 0.80% by mass.

[0024] The mass ratio (A) / (E) of component (A) and component (E) in the aerosol stock solution is preferably 0.01 or more, more preferably 0.03 or more, still more preferably 0.1 or more, from the viewpoint of uniform coatability of the preparation. Also, it is preferably 60 or less, more preferably 10 or less, still more preferably 4 or less. The specific range of the mass ratio (A) / (E) of component (A) and component (E) in the aerosol stock solution is preferably 0.01 to 60, more preferably 0.03 to 10, still more preferably 0.1 to 4.

[0025] The mass ratio (B) / (E) of component (B) and component (E) in the aerosol stock solution is preferably 0.01 or more, more preferably 0.05 or more, still more preferably 0.1 or more, from the viewpoint of reducing skin irritation. Also, it is preferably 100 or less, more preferably 14 or less, still more preferably 5 or less. The specific range of the mass ratio (B) / (E) of component (B) and component (E) in the aerosol stock solution is preferably 0.01 to 100, more preferably 0.05 to 14, still more preferably 0.1 to 5.

[0026] 〔Other optional components〕 In the aerosol stock solution, as components other than the above components, components usually used in external skin preparations may be appropriately blended. Examples of such components include oily agents that are liquid at 25°C, polyhydric alcohols, thickeners, preservatives, powders, ethanol, antioxidants, pigments, fragrances, moisturizers, blood circulation promoters, cooling agents, antiperspirants, bactericides, skin brighteners, anti-inflammatory agents, skin activators, and the like. Note that each of these agents is not limited to its use as such an agent, and can be diverted to other uses or used in combination with other uses according to the purpose. For example, an antiperspirant may be used as a fragrance, or may be used as an agent that exhibits the effects of an antiperspirant and a fragrance.

[0027] The polyhydric alcohol may be any one that is usually used in ordinary cosmetics. Examples 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 polyhydric alcohols having three or more hydroxyl groups such as glycerin and sorbitol. Among these, from the viewpoint of improving the penetration feeling of the discharged agent into the skin and the uniform coating property, glycerin and dihydric polyols are preferable, glycerin, propylene glycol, propanediol, 1,3-butylene glycol, 1,3-propanediol, and dipropylene glycol are more preferable, glycerin, 1,3-propanediol, and dipropylene glycol are still more preferable, and it is still more preferable to contain glycerin and dipropylene glycol.

[0028] From the viewpoint of improving the penetration feeling of the discharged agent into the skin and the uniform coating property, the content of the polyhydric alcohol in the aerosol stock solution is preferably 1% by mass or more, more preferably 2% by mass or more, still more preferably 5% by mass or more, still more preferably 10% by mass or more, and is preferably 50% by mass or less, more preferably 40% by mass or less, still more preferably 30% by mass or less, still more preferably 20% by mass or less. The specific range of the content of the polyhydric alcohol in the aerosol stock solution is preferably 1 to 50% by mass, more preferably 2 to 40% by mass, still more preferably 5 to 30% by mass, still more preferably 10 to 20% by mass.

[0029] ● Propellant 〔Component (D): Carbon dioxide gas〕 In the present invention, carbon dioxide gas as component (D) is contained as a propellant. As the propellant, in addition to carbon dioxide gas, other propellants can also be used in combination. Examples of propellants other than carbon dioxide gas include liquefied petroleum gas (ethane, propane, ethylene, isobutane, normal butane, propylene, etc., mixed gases thereof (for example, mixed gases of isobutane and propane, propane and butane, etc.)), ether-based propellants (dimethyl ether, etc.), fluorocarbons (fluorocarbons, chlorofluorocarbons, bromochlorofluorocarbons, etc.), compressed gases (nitrogen, air, mixed gases thereof, etc.), and Freon gases (monochlorodifluoroethane, tetrafluoroethane, etc.). Among them, nitrogen, dimethyl ether, and liquefied petroleum gas are preferred. When other propellants are used in combination with the carbon dioxide gas of component (D), any of them can be used alone or in combinations of two or more.

[0030] When a propellant other than the carbon dioxide gas of component (D) is used in combination as the propellant, from the viewpoint of not impairing the effect of carbon dioxide gas, the ratio of the carbon dioxide gas of component (D) in all the propellants is preferably 20% or more, more preferably 40% or more, still more preferably 60% or more, and still more preferably 80% or more on a volume basis in the gaseous state (1013.25 hPa, 25 °C).

[0031] ● Carbonated aerosol topical skin preparation The carbonated aerosol topical skin preparation of the present invention can be produced by preparing an aerosol stock solution containing components (A) to (C) and filling it into a pressure-resistant container together with a propellant containing component (D). As the form of the ejection, it is preferably a foam type that ejects in a foamy state.

[0032] The ratio of carbon dioxide gas to 100 parts by mass of the aerosol stock solution is preferably 0.01 part by mass or more, more preferably 0.10 part by mass or more, still more preferably 0.125 part by mass or more, still more preferably 0.25 part by mass or more, still more preferably 0.5 part by mass or more, still more preferably 1.0 part by mass or more, and preferably 5.0 parts by mass or less, more preferably 3.0 parts by mass or less, from the viewpoints of improving the solubility of carbon dioxide gas in the aerosol stock solution, foam viscosity, and injectability.

[0033] Also, the pH of the mixture of the aerosol stock solution and the propellant containing carbon dioxide gas as component (D) is adjusted to 4.5 or more and 7.0 or less by the pH adjuster of the component (B) from the viewpoint of improving the storage stability of the heparin-like substance. The pH of the mixture of the aerosol stock solution and the propellant is preferably 5.0 or more, more preferably 5.5 or more, and preferably 6.5 or less, more preferably 6.0 or less, from the viewpoint of keeping the pH of the skin after application weakly acidic. The pH of the mixture of the aerosol stock solution and the propellant can be determined by putting the aerosol stock solution added with an indicator into an aerosol-compatible bottle, filling it with the propellant, and comparing the color tone with a standard product. As the indicator, bromophenol blue, bromocresol green, methyl red, bromothymol blue, etc. can be used.

[0034] When the carbonated aerosol topical skin preparation of the present invention is of the foam type, the viscosity of the ejected foam is preferably 0.1 Pa·s or more, more preferably 0.5 Pa·s or more, still more preferably 1.0 Pa·s or more, and preferably 50 Pa·s or less, more preferably 40 Pa·s or less, still more preferably 30 Pa·s or less, from the viewpoint of reducing irritation to the skin. Here, the viscosity of the ejected foam shall be measured using a B-type viscometer (for example, VISCOMETER TVB-10, manufactured by Toki Sangyo Co., Ltd.) under the conditions of rotor No. 3, 12 rpm, 25 °C, and 10 seconds.

[0035] 〔Usage method〕 The carbonated aerosol topical skin preparation of the present invention is applied in an appropriate amount to the skin, preferably the whole body skin excluding the scalp, more preferably any of the face, body, limbs, etc., and even more preferably the skin of the hands and feet. It may be applied by hand and spread over the target area, or directly ejected onto the target area. In the case of the foam type, it is preferably applied by hand without crushing the foam. In particular, it is preferably applied to thick and easily dried areas such as the hands, feet, their fingers, heels, elbows, knees, etc. The application amount is preferably about 1 g for both hands.

[0036] Regarding the above-described embodiments, the following preferred embodiments of the present invention are further disclosed.

[0037] <1>A carbonated aerosol topical skin preparation comprising an aerosol stock solution containing the following components (A) to (C) and a propellant containing component (D), wherein the pH of the mixed solution of the aerosol stock solution and the propellant is 4.5 or more and 7.0 or less. (A) Heparin-like substance (B) pH adjuster (C) Water (D) Carbon dioxide gas

[0038] <2>The carbonated aerosol topical skin preparation according to <1>, wherein the content of component (A) in the aerosol stock solution is preferably 0.05% by mass or more, more preferably 0.07% by mass or more, still more preferably 0.1% by mass or more, and preferably 0.6% by mass or less, more preferably 0.5% by mass or less, still more preferably 0.4% by mass or less.

[0039] <3>The carbonated aerosol topical skin preparation according to <1> or <2>, wherein component (B) is preferably at least one compound 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, and more preferably at least one compound selected from the group consisting of organic acids, organic acid salts, amino acids, amino acid salts, amines, and inorganic bases.

[0040] <4> The content of component (B) in the aerosol stock solution is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.15% by mass or more, and is preferably 1.0% by mass or less, more preferably 0.7% by mass or less, still more preferably 0.5% by mass or less. The carbonated aerosol skin external preparation according to any one of <1> to <3>.

[0041] <5> The mass ratio (A) / (B) of component (A) and component (B) in the aerosol stock solution is preferably 0.05 or more, more preferably 0.1 or more, still more preferably 0.2 or more, and is preferably 12 or less, more preferably 5 or less, still more preferably 2.5 or less. The carbonated aerosol skin external preparation according to any one of <1> to <4>.

[0042] <6> The content of component (C) in the aerosol stock solution is preferably 10% by mass or more, more preferably 20% by mass or more, still more preferably 40% by mass or more, and is preferably 90% by mass or less, more preferably 85% by mass or less, still more preferably 80% by mass or less. The carbonated aerosol skin external preparation according to any one of <1> to <5>.

[0043] <7> Preferably, further, the carbonated aerosol skin external preparation according to any one of <1> to <6> contains a water-soluble polymer as component (E) in the aerosol stock solution.

[0044] <8> Component (E) is preferably a water-soluble polymer having a sugar skeleton, more preferably a cellulose-based polymer, still more preferably at least one selected from hydroxypropylmethylcellulose, hydroxypropylmethylcellulose stearoxy ether, and hydroxyethylcellulose. The carbonated aerosol skin external preparation according to <7>.

[0045] <9> The content of component (E) in the aerosol stock solution is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, still more preferably 0.10% by mass or more, and even more preferably 0.20% by mass or more, and is preferably 5.0% by mass or less, more preferably 2.0% by mass or less, still more preferably 1.0% by mass or less, and even more preferably 0.80% by mass or less, which is the carbonated aerosol skin external preparation according to <7> or <8>.

[0046] <10> The mass ratio (A) / (E) of component (A) and component (E) in the aerosol stock solution is preferably 0.01 or more, more preferably 0.03 or more, still more preferably 0.1 or more, and is preferably 60 or less, more preferably 10 or less, still more preferably 4 or less, which is the carbonated aerosol skin external preparation according to any one of <7> to <9>.

[0047] <11> The mass ratio (B) / (E) of component (B) and component (E) in the aerosol stock solution is preferably 0.01 or more, more preferably 0.05 or more, still more preferably 0.1 or more, and is preferably 100 or less, more preferably 14 or less, still more preferably 5 or less, which is the carbonated aerosol skin external preparation according to any one of <7> to <10>.

[0048] <12> Preferably, further, the carbonated aerosol skin external preparation according to any one of <1> to <11> contains a polyhydric alcohol in the aerosol stock solution.

[0049] <13> The polyhydric alcohol is preferably at least one selected from glycerin and dihydric polyols, more preferably at least one selected from glycerin, propylene glycol, propanediol, 1,3 - butylene glycol, 1,3 - propanediol, and dipropylene glycol, still more preferably at least one selected from glycerin, 1,3 - propanediol, and dipropylene glycol, and even more preferably contains glycerin and dipropylene glycol, which is the carbonated aerosol skin external preparation according to <12>.

[0050] <14> The content of the polyhydric alcohol in the aerosol stock solution is preferably 1% by mass or more, more preferably 2% by mass or more, still more preferably 5% by mass or more, still more preferably 10% by mass or more, and is preferably 50% by mass or less, more preferably 40% by mass or less, still more preferably 30% by mass or less, still more preferably 20% by mass or less, which is the carbonated aerosol skin external preparation described in <12> or <13>.

[0051] <15> The pH of the mixed solution of the aerosol stock solution and the propellant is preferably 5.0 or more, more preferably 5.5 or more, and is preferably 6.5 or less, more preferably 6.0 or less, which is the carbonated aerosol skin external preparation described in any one of <1> to <14>.

[0052] <16> Preferably, it is the carbonated aerosol skin external preparation described in any one of <1> to <15>, which is discharged in a foamy state.

Examples

[0053] Examples 1 to 22, Comparative Examples 1 to 3 Aerosol stock solutions were prepared according to the formulations shown in Tables 1 to 2, filled into an aluminum pressure-resistant container together with a propellant (carbon dioxide gas, isopentane, LPG), and carbonated aerosol skin cosmetics were manufactured. Regarding these carbonated aerosol skin cosmetics, the stability of the heparin-like substance and the usability during application were evaluated according to the following methods and criteria.

[0054] The pH of the mixed solution of the aerosol stock solution and the propellant was determined by putting the aerosol stock solution added with an indicator into an aerosol-compatible bottle, filling it with the propellant, and comparing the color tone with a standard product. As the indicator, bromophenol blue (the pH of the standard product is 4.0, 4.5, 4.7), bromocresol green (the pH of the standard product is 5.0, 5.3, 5.5), methyl red (the pH of the standard product is 5.0, 5.3, 5.5), etc. were used.

[0055] <Stability of heparin-like substance> The residual rate of the heparin-like substance was calculated by comparing the quantitative value of the heparin-like substance when each aerosol topical skin preparation was stored in a thermostat at 45°C for 3 months with the initial quantitative value, and evaluated according to the following evaluation criteria. The quantification of the heparin-like substance was carried out using the ultraviolet-visible absorbance method with o-toluidine blue. Residual rate of heparin-like substance (%) = (Quantitative value after storage) / (Initial quantitative value) × 100 A: Residual rate of heparin-like substance is 97% or more B: Residual rate of heparin-like substance is 95% or more and less than 97% C: Residual rate of heparin-like substance is 90% or more and less than 95% D: Residual rate of heparin-like substance is 80% or more and less than 90% E: Residual rate of heparin-like substance is less than 80%

[0056] <Foam quality> Approximately 1 g of the aerosol topical skin preparation was discharged onto the palm from the pressure-resistant container, and the appearance of the foam 10 seconds later was evaluated by 5 professional panelists according to the criteria of fine texture (2 points) / coarse-textured foam (1 point) / no foam formation (0 point), and the total score of the evaluation points was shown in the table.

[0057] <Feeling during application> 0.5 g of the aerosol topical skin preparation discharged from the pressure-resistant container was applied to the forearm, and the skin sensation 5 minutes after spreading was evaluated by 5 professional panelists according to the criteria of feeling no tightness (2 points) / hardly feeling tightness (1 point) / feeling tightness (0 point), and the total score of the evaluation points was shown in the table.

[0058]

Table 1

[0059]

Table 2

[0060] *1: Metroose 90SH-15000 (manufactured by Shin-Etsu Chemical Co., Ltd.)

Claims

1. It consists of an aerosol stock solution containing the following components (A) to (C) and (E) and a propellant containing component (D), The mass ratio (A) / (B) of component (A) to component (B) is 0.2 to 30.00, The mass ratio (A) / (E) of component (A) to component (E) is 0.1 to 4, The pH of the mixed solution of the aerosol stock solution and the propellant is 4.8 or more and 7.0 or less, The ratio of component (D) in the total propellant is 60% or more based on the volume standard in the gaseous state (1013.25 hPa, 25 °C), A carbonated aerosol topical skin preparation discharged in a foamy state. (A) Heparin-like substance 0.05% by mass or more and 0.6% by mass or less (B) pH adjuster 0.05% by mass or more and 1.2% by mass or less (C) Water (D) Carbon dioxide gas (E) Cellulosic polymer 0.20% by mass or more and 0.80% by mass or less

2. The carbonated aerosol topical skin preparation according to claim 1, wherein component (B) is at least one compound selected from the group consisting of organic acids, organic acid salts, amino acids, amino acid salts, amines, and inorganic bases.

3. The carbonated aerosol topical skin preparation according to claim 1 or 2, wherein component (E) is hydroxypropyl methylcellulose.

4. The carbonated aerosol topical skin preparation according to any one of claims 1 to 3, wherein the mass ratio (B) / (E) of component (B) to component (E) is 0.01 or more and 5 or less.

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