Topical liquid composition for application in foam form

Abstract

To provide a topical liquid composition that contains a heparin-like substance and exhibits superior sensation upon use.SOLUTION: A topical liquid composition to be applied in foam form is prepared, the composition containing (A) a heparin-like substance; and (B) at least one or more compounds selected from the group consisting of glycyrrhetinic acid, derivatives of glycyrrhetinic acid and / or salts thereof, allantoin, tocopherol acetate, chlorpheniramine maleate, diphenhydramine or a salt thereof, lidocaine or a salt thereof, dibucaine or a salt thereof, and crotamiton.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a liquid topical composition for application in the form of a foam. More particularly, to a liquid topical composition for application in the form of a foam. The present invention relates to a liquid composition for external use that contains a similar substance and that is foamy when applied. [Background technology]

[0002] Heparinoids have moisturizing and anti-inflammatory properties and are widely used in medicines. The skin moisturizing effect of heparin analogues reduces dry skin symptoms. The blood circulation promoting effect of the similar substance promotes blood circulation in the area where it is used, and relieves pain and swelling caused by poor circulation. This will reduce the risk of

[0003] For example, Patent Document 1 discloses a compound containing vitamin A, edetic acid or its salt, and a heparinoid. The present invention discloses a liquid composition for external application to the skin, which comprises: It is described that the product can contain a stable amount of vitamin A. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2012-36183 Summary of the Invention [Problem to be solved by the invention]

[0005] Heparinoids may be used on rough skin or delicate areas, but Although there is sufficient knowledge regarding the feel of use of foam-type external liquid compositions containing phosphorus analogues, This is not the case.

[0006] The present invention has been made in view of the above, and provides a heparin analogue having a good feeling when used. The present invention aims to provide a liquid composition for external use to be applied in the form of a foam containing a compound. [Means for solving the problem]

[0007] Foam-type topical preparations are known for their unique softness and ease of use, which are different from creams and liquids. On the other hand, there are many studies on the properties of foam containing active ingredients such as heparinoids. Detailed consideration is required.

[0008] The present invention aims to provide a liquid composition for external use that is applied in the form of a foam and has an excellent feel when used. The present inventors have investigated the effects of (A) heparinoids and (B) glycyrrhetinic acid, glycyrrhetinic acid, and glycyrrhetinic acid. Derivatives of cyrrhetinic acid and / or their salts, allantoin, tocopherol acetate, malic acid, Chlorpheniramine leate, diphenhydramine and / or its salts, lidocaine and / or or a salt thereof, dibucaine and / or a salt thereof, and crotamiton. By containing one or more compounds, it is possible to produce a foam that spreads easily when applied in foam form. The present invention has been accomplished based on the discovery that a liquid composition for external use that can provide the above-mentioned properties can be obtained.

[0009] That is, the present invention provides the following liquid compositions for external use. Section 1. (A) heparinoids; and (B) Glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or their salts, allantoin Inosin, tocopheryl acetate, chlorpheniramine maleate, diphenhydramine and / or or its salts, lidocaine and / or its salts, dibucaine and / or its salts, and crotami one or more compounds selected from the group consisting of t; A liquid composition for external use, which contains the above and is contained in a foam-discharging container. Section 2. Item 1, wherein the foam-discharging container is an aerosol container containing a propellant. . Section 3. (A) heparinoids; and (B) Glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or their salts, allantoin Inosin, tocopheryl acetate, chlorpheniramine maleate, diphenhydramine and / or or its salts, lidocaine and / or its salts, dibucaine and / or its salts, and crotami one or more compounds selected from the group consisting of t; A liquid composition for external use to be applied in the form of a foam, comprising: Section 4. Item 3. The foam is formed by an aerosol container for foam discharging containing a propellant. Liquid composition for use. Section 5. Item 2 or 4, wherein the mass ratio of the liquid composition for external use to the propellant is 50:50 to 99:1. The liquid composition for external use described above. Section 6. Item 6. The liquid composition for external use according to any one of Items 1 to 5, further comprising ethanol.

[0010] The present invention also provides the following methods. Section 7. (A) heparinoids; and (B) Glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or their salts, allantoin Inosin, tocopheryl acetate, chlorpheniramine maleate, diphenhydramine and / or or its salts, lidocaine and / or its salts, dibucaine and / or its salts, and crotami one or more compounds selected from the group consisting of t; A method for forming foam with good spreadability by using the coexistence of [Effects of the Invention]

[0011] According to the present invention, a liquid composition for external use that can be applied in the form of a spreadable foam can be provided. Cut. DETAILED DESCRIPTION OF THE INVENTION

[0012] [External liquid composition] The present invention relates to (A) a heparinoid; and (B) Glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or their salts, allantoin Inosin, tocopheryl acetate, chlorpheniramine maleate, diphenhydramine and / or or its salts, lidocaine and / or its salts, dibucaine and / or its salts, and crotami one or more compounds selected from the group consisting of t; The present invention relates to a liquid composition for external use, which contains the above and is contained in a foam-discharging container.

[0013] The present invention further comprises: (A) a heparinoid; and (B) Glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or their salts, allantoin Inosin, tocopheryl acetate, chlorpheniramine maleate, diphenhydramine and / or or its salts, lidocaine and / or its salts, dibucaine and / or its salts, and crotami one or more compounds selected from the group consisting of t; The present invention relates to a liquid composition for external use, which is to be applied in the form of a foam and contains

[0014] ((A) Heparinoids) Heparinoids are substances called mucopolysaccharide polysulfates or heparinoids. It is a repeating disaccharide structure consisting of D-glucuronic acid and N-acetyl-D-galactosamine. It is a mucopolysaccharide in which a large amount of sulfate groups have been introduced. Heparinoids as specified in the official pharmaceutical specifications are preferred.

[0015] The amount (%) of organic sulfate groups in the heparinoid is not particularly limited, but it may be increased if it has moisturizing properties. From the viewpoint of efficacy, 25 to 38% is preferable. It can be measured by the method described in the section on "heparinoids" in the Non-Pharmacopoeial Drug Specifications.

[0016] (A) The content of the heparinoid is, from the viewpoint of exhibiting the effect of the present invention more significantly, The content is preferably 0.001% by mass or more, more preferably 0.001% by mass or more, based on the total amount of the liquid composition. It is 0.01% by mass or more, more preferably 0.1% by mass or more, and even more preferably The content of the heparin-like substance is 0.2% by mass or more, and particularly preferably 0.3% by mass or more. From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of , preferably 1% by mass or less, more preferably 0.5% by mass or less, and even more preferably The content of (A) heparinoids relative to the total amount of the liquid composition for external use is 0.3% by mass or less. The content is preferably 0.001% by mass to 1% by mass from the viewpoint of more significantly exhibiting the effects of the present invention. % by mass, more preferably 0.01% to 0.5% by mass, and even more preferably 0.1% by mass. The content is preferably 0.2% to 0.3% by mass, more preferably 0.2% to 0.3% by mass. 3% by mass is most preferred.

[0017] (B) Glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or salts thereof, alanine Tocopherol acetate, chlorpheniramine maleate, diphenhydramine and and / or its salts, lidocaine and / or its salts, dibucaine and / or its salts, and crotaline one or more compounds selected from the group consisting of mittens The following substances can be used as the component (B) of the present invention, and these are particularly That is, glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or its derivatives These salts, allantoin, tocopheryl acetate, chlorpheniramine maleate, diphenhydramine benzocaine and / or its salts, lidocaine and / or its salts, dibucaine and / or its salts and crotamiton.

[0018] ((B-1) Glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or salts thereof) Glycyrrhetinic acid or its derivatives used in the present invention can be used in pharmaceuticals, quasi-drugs, cosmetics, etc. There are no particular restrictions as long as the grade is the same as that used in the art. The salt of the conductor may be any pharmacologically acceptable salt, for example, sodium salt, potassium salt, etc. Alkali metal salts such as ammonium salts; alkaline earth metal salts such as calcium salts and magnesium salts metal salts; triethylamine, triethylamine, triethanolamine, morpholine, piperazine , pyrrolidine, tripyridine, picoline, and other amine salts. Derivatives of cyrrhetic acid include glycosides of glycyrrhetinic acid, among which glycyrrhetinic acid Among these, glycyrrhizic acid, glycyrrhizic acid Alkali metal salts of glycyrrhizinic acid are preferred, and dipotassium glycyrrhizinate is more preferred. glycyrrhetinic acid derivatives and / or salts thereof may be used alone. Alternatively, two or more types may be used in combination.

[0019] ((B-2) Allantoin) Allantoin used in the present invention is used in pharmaceuticals, quasi-drugs, cosmetics, etc. There are no particular limitations as long as it is of a certain grade.

[0020] ((B-3) Tocopherol acetate) The tocopherol acetate used in the present invention is a compound used in pharmaceuticals, quasi-drugs, cosmetics, etc. There are no particular restrictions as long as the grade is acceptable.

[0021] ((B-4) Chlorpheniramine maleate) Chlorpheniramine maleate used in the present invention is suitable for use in pharmaceuticals, quasi-drugs, cosmetics, etc. There are no particular limitations on the grade of the material as long as it is of the grade used in the art.

[0022] ((B-5) Diphenhydramine and / or its salts) Diphenhydramine used in the present invention is a compound used in medicines, quasi-drugs, cosmetics, etc. There are no particular restrictions as long as the grade is suitable for use. Any commercially acceptable salt may be used, for example, hydrochloride, citrate, succinate, tartrate, Fumarate, maleate, salicylate, diphenyldisulfonate, tannate, Examples of acid addition salts include lauryl sulfate and sulfate. Diphenhydramine and / or its salts may be used alone. Alternatively, two or more of them may be used in combination.

[0023] ((B-6) Lidocaine and / or its salt, (B-7) Dibucaine and / or its salt) The lidocaine or dibucaine used in the present invention is used in pharmaceuticals, quasi-drugs, cosmetics, etc. There are no particular restrictions as long as the grade is in accordance with the regulations. For example, a pharmacologically acceptable salt may be used, such as a hydrochloride, a citrate, or a succinate. , tartrate, fumarate, maleate, salicylate, diphenyldisulfonate, Acid addition salts such as benzoate, lauryl sulfate, and sulfate are also included. Caine hydrochloride and dibucaine hydrochloride are preferred. Lidocaine and / or its salts, dibucaine and / or salts thereof may be used alone or in combination of two or more. It may also be used.

[0024] ((B-8) Crotamiton) The crotamiton used in the present invention is used in pharmaceuticals, quasi-drugs, cosmetics, etc. There are no particular limitations as long as it is of a certain grade.

[0025] From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of component (B) in the liquid composition for external use is It is preferably 0.2% by mass or more, more preferably 0.5% by mass or more, based on the total amount. The content is more preferably 0.7% by mass or more, and particularly preferably 1.2% by mass or more. From the viewpoint of more significantly exhibiting the effects of the present invention, the total content of component (B) is The amount is preferably 10% by weight or less, more preferably 6% by weight or less, The content is more preferably 3% by weight or less, and particularly preferably 1.7% by weight or less. The total content of component (B) relative to the total amount of the composition is preferably 0.1 to 0.5% by weight, from the viewpoint of more significantly exhibiting the effects of the present invention. Therefore, the content is preferably 0.2% by mass to 10% by mass, and more preferably 0.5% by mass to 6% by mass. %, more preferably 0.7% by mass to 3% by mass, and particularly preferably 1.2% by mass to 1.7% by mass. % by volume.

[0026] In the liquid composition for external use of the present invention, from the viewpoint of more significantly exhibiting the effects of the present invention, The ratio of the total amount of component (B) to component (A) is, for example, The amount is preferably 0.3 parts by mass or more, more preferably 1 part by mass or more, and Preferably, it is 2 parts by mass or more, even more preferably 3 parts by mass or more, and particularly preferably 5 parts by mass or more. The total content of the component (B) is 100 parts by mass or more from the viewpoint of more significantly exhibiting the effects of the present invention. The amount is preferably 35 parts by mass or less per part by mass of the (A) component, and more preferably or 25 parts by mass or less, more preferably 15 parts by mass or less, particularly preferably parts by mass or less. In the liquid composition for external use of the present invention, the ratio of component (B) to component (A) is, for example, For example, the amount is preferably 0.3 to 35 parts by mass, and more preferably 1 to 25 parts by mass, per part by mass of the component (A). parts by mass is more preferred, 2 to 15 parts by mass is even more preferred, and 3 to 7 parts by mass is particularly preferred. stomach.

[0027] (B) component (B-1) glycyrrhetinic acid, a derivative of glycyrrhetinic acid, and / or When these salts are contained, from the viewpoint of significantly exhibiting the effects of the present invention, glycyrrhetinic acid ... The content of the derivatives of luretic acid and / or their salts is, based on the total amount of the liquid composition for external use, It is 0.05% by mass to 1% by mass, more preferably 0.1% by mass to 0.5% by mass, and further The content is preferably 0.3% by mass to 0.5% by mass.

[0028] In the liquid composition for external use of the present invention, the ratio of component (B-1) to component (A) is, for example, For example, the amount is preferably 0.1 to 4 parts by mass, and more preferably 0.5 to 4 parts by mass, per part by mass of the (A) component. Parts by mass are more preferred, 1 to 4 parts by mass are even more preferred, and 1.5 to 3.5 parts by mass are particularly preferred. preferable.

[0029] For example, when component (B) contains (B-2) allantoin, the effects of the present invention are significantly exhibited. From this viewpoint, the content of allantoin is preferably 0.0% based on the total amount of the liquid composition for external use. 2% by mass to 0.2% by mass, more preferably 0.05% by mass to 0.2% by mass, and further The content is preferably 0.1% by mass to 0.2% by mass.

[0030] In the liquid composition for external use of the present invention, the ratio of component (B-2) to component (A) is, for example, For example, the amount is preferably 0.01 to 2 parts by mass, and more preferably 0.1 to 2 parts by mass, per part by mass of the (A) component. parts by mass is more preferred, 0.2 to 1 part by mass is even more preferred, and 0.5 to 0.7 parts by mass is particularly preferred.

[0031] For example, when the component (B) contains (B-3) tocopherol acetate, the effects of the present invention are significantly enhanced. From the viewpoint of achieving the above, the content of tocopherol acetate relative to the total amount of the liquid composition for external use is preferably or 0.001% by mass to 0.5% by mass, more preferably 0.05% by mass to 0.5 % by mass, more preferably 0.1% to 0.5% by mass, and particularly preferably 0.27% by mass The content is about 0.5% by mass.

[0032] In the liquid composition for external use of the present invention, the ratio of the component (B-3) to the component (A) is, for example, For example, the amount is preferably 0.01 to 10 parts by mass, and more preferably 0.1 to 10 parts by mass, per part by mass of the (A) component. 5 parts by mass is more preferable, 0.5 to 3.5 parts by mass is even more preferable, and 1.5 to 2 parts by mass is even more preferable. Particularly preferred is the

[0033] For example, when component (B) contains (B-4) chlorpheniramine maleate, In order to achieve a significant effect, the content of chlorpheniramine maleate is preferably 0. The content is 0.2% by mass to 2% by mass, and more preferably 0.5% by mass to 1% by mass.

[0034] In the liquid composition for external use of the present invention, the ratio of component (B-4) to component (A) is, for example, For example, the amount is preferably 1 to 4 parts by mass, more preferably 2 to 4 parts by mass, per 1 part by mass of the (A) component. More preferable.

[0035] For example, when component (B) contains (B-5) diphenhydramine and / or a salt thereof, In order to achieve the effects of the present invention more remarkably, the content of diphenhydramine and / or a salt thereof is It is preferably 0.2% by mass to 2% by mass, more preferably is 0.5% by mass to 1% by mass.

[0036] In the liquid composition for external use of the present invention, the ratio of component (B-5) to component (A) is, for example, For example, the amount is preferably 1 to 4 parts by mass, more preferably 2 to 4 parts by mass, per 1 part by mass of the (A) component. More preferable.

[0037] For example, when component (B) contains (B-6) lidocaine and / or a salt thereof, the effectiveness of the present invention is From the viewpoint of achieving a significant effect, the content of lidocaine and / or a salt thereof is preferably 0.2 The content is preferably 1% to 2% by mass, and more preferably 1% to 2% by mass.

[0038] In the liquid composition for external use of the present invention, the ratio of component (B-6) to component (A) is, for example, For example, the amount is preferably 0.1 to 7 parts by mass, and more preferably 1 to 7 parts by mass, per part by mass of the (A) component. is more preferable, and 5 to 7 parts by mass is even more preferable.

[0039] For example, when component (B) contains (B-7) dibucaine and / or a salt thereof, the effectiveness of the present invention is From the viewpoint of achieving a significant effect, the content of dibucaine and / or a salt thereof is preferably 0.2 The content is preferably 1% to 2% by mass, and more preferably 1% to 2% by mass.

[0040] In the liquid composition for external use of the present invention, the ratio of component (B-7) to component (A) is, for example, For example, the amount is preferably 0.1 to 7 parts by mass, and more preferably 1 to 7 parts by mass, per part by mass of the (A) component. is more preferable, and 5 to 7 parts by mass is even more preferable.

[0041] For example, when component (B) contains (B-8) crotamiton, the effects of the present invention are significantly exhibited. From this viewpoint, the content of crotamiton is preferably 2% by mass based on the total amount of the liquid composition for external use. % to 10% by mass, and more preferably 2% to 5% by mass.

[0042] In the liquid composition for external use of the present invention, the ratio of component (B-8) to component (A) is, for example, For example, the amount is preferably 5 to 40 parts by mass, and more preferably 10 to 20 parts by mass, per part by mass of the component (A). Part is more preferred.

[0043] (ethanol) In the present invention, in addition to the (A) heparinoid substance and the above-mentioned (B) component, Any known component that can be used as a drug, quasi-drug, cosmetic, etc., within the scope that does not impair the The liquid composition for external use can contain the following optional components. Ethanol may be included.

[0044] The ethanol used in the liquid composition for external use of the present invention is used in medicines, quasi-drugs, cosmetics, etc. There are no particular limitations as long as the grade and quality are in use. The ethanol used is, for example, 95% ethanol, 99% ethanol (absolute ethanol), ) etc. can be used as appropriate.

[0045] The content of ethanol is 0.01% based on the total amount of the external liquid composition from the viewpoint of foam formation and usability. It is preferable that the content is more than 100% by mass, more preferably 0.01% by mass or more, and further The content of ethanol is preferably 0.1% by mass or more from the viewpoint of foam formation and feeling when used. Therefore, it is preferably 5% by mass or less, more preferably 3% by mass or less, based on the total amount of the liquid composition for external use. % by mass or less, and more preferably 1% by mass or less, based on the total amount of the liquid composition for external use. The content of alcohol is preferably 0.01 to 3 mass %, more preferably 0.1 to 1 mass %. % by volume.

[0046] In the liquid composition for external use of the present invention, the ratio of ethanol to component (A) is adjusted to achieve the desired feeling when used. From this viewpoint, for example, the content of ethanol per 1 part by mass of the content of the component (A) is preferably Preferably, it is 0.033 to 17 parts by mass, and more preferably 0.33 to 10 parts by mass.

[0047] [container] The liquid composition for external use of the present invention is preferably contained in a foam-dispensing container.

[0048] Here, the foam dispensing container is preferably a pump foamer container or a foam dispensing container containing a propellant. It is an aerosol container, more preferably a foam-discharging aerosol container containing a propellant. That is, the liquid composition for external use is filled into a container together with a propellant, and the foam formed after spraying from the container is Particularly preferred is a foaming aerosol container that allows the spray to be applied to the skin. The agent may be carbon dioxide (carbon dioxide), nitrogen, liquefied petroleum gas (LPG), or dimethyl ether. Dimethyl ether (DME) is preferably used.

[0049] The material of the container for filling the liquid composition for external use of the present invention is not particularly limited. Any container that can be used as a container for quasi-drugs or cosmetics. Pump former container As for the material, for example, a part or all, preferably all, of the surface that comes into contact with the liquid composition for external use is made of polypropylene. Polyolefin resin, acrylic resin, polyester, polycarbonate, fluorine resin, poly Polyvinyl chloride, polyamide, ABS resin, AS resin, polyacetal, modified polyphenylene Polyether, polyarylate, polysulfone, polyimide, cellulose acetate, aluminum A container made of at least one material selected from the group consisting of aluminum and glass. Examples include vessels.

[0050] The material of the foam-discharging aerosol container containing the propellant may be, for example, aluminum, steel or brass. Examples of metal containers include those made of metal such as liquefied petroleum (RIK), etc. The inner surface of the metal container is coated with epoxy resin, phenolic resin, etc. It may be coated with a resin or a polyamide-imide resin.

[0051] Here, when a foam discharging container containing a propellant is used, it is not limited, but preferably, The mass ratio of the liquid composition to the propellant is 50:50 to 99:1, preferably 85:15 to 97: 3, more preferably 90:10 to 95:5, and even more preferably 92:8 to 93:7 It is preferable to fill the mixture into a container.

[0052] [Dosage form] The liquid composition for external use of the present invention is a liquid preparation that can be used as a medicine, a quasi-drug, etc., and forms foam. Although there is no limitation as long as it is a liquid, it is usually provided in the form of an aqueous composition. The water-soluble composition is a composition in which the proportion of water or a water-soluble solvent in the total amount of the composition is 10% by mass or more. From the viewpoint of the stability of the preparation or the feeling of use, it is preferably 50% by mass or more, and more preferably Preferably, it refers to a dosage form containing 70% by mass or more.

[0053] The preparations are prepared by mixing the ingredients in accordance with the General Provisions of the 17th Edition of the Japanese Pharmacopoeia or in accordance with the same. It can be manufactured by the following.

[0054] [Manufacturing method] The liquid composition for external use of the present invention can be produced by a known method. Sterilization and filtration steps may be included.

[0055] [Base, carrier, or other ingredient] The liquid composition for external use of the present invention can be used in a variety of applications, including medicines, quasi-drugs, and the like, as long as the effects of the present invention are not impaired. It can be formulated by mixing known ingredients that can be used in cosmetics, etc. The ingredients include, for example, surfactants, thickeners, oils, moisturizing ingredients, preservatives, antioxidants, and cooling agents. It is possible to blend additives such as chelating agents, pH adjusters, buffers, fragrances, coloring agents, and pigments. These additives can be used alone or in combination of two or more.

[0056] The surfactant may be, for example, a nonionic surfactant. Examples of the anti-aging agent include sorbitan fatty acid esters, propylene glycol fatty acid esters, esters, castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, Alkylene alkyl ether, glycerin fatty acid ester, polyglycerin fatty acid ester Examples include silicone surfactants and polyoxyethylene lauryl alcohol ether. Examples of sorbitan fatty acid esters include sorbitan monoisostearate, Sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate Diglycerol sorbitan penta-2-ethylhexyl ester, tetra-2-ethylhexyl ester diglycerol sorbitan xylate, sorbitan sesquioleate, etc., and Examples of propylene glycol fatty acid esters include propylene glycol monostearate. Examples include propylene glycol fatty acid esters such as propylene glycol, and castor oil derivatives. Examples include polyoxyethylene hydrogenated castor oil and polyoxyethylene castor oil. Examples of polyoxyethylene sorbitan fatty acid esters include poly(monolauryl)ate, Oxyethylene (20) sorbitan (polysorbate 20), polyoxyethylene monostearate Diethylene (20) sorbitan (polysorbate 60), polyoxyethylene monooleate Len (20), Sorbitan (Polysorbate 80), Polyoxyethylene Isostearate (20) Sorbitan, etc., and examples of polyoxyalkylene alkyl ethers include, for example, For example, polyoxyethylene monococonut oil fatty acid glyceryl, glycerin alkyl ether, Alkyl glucoside, polyoxyethylene cetyl ether, polyoxyethylene lauryl Ether, Polyoxyethylene Monostearate, Polyoxyethylene Monooleate, Examples of glycerin fatty acid esters include: Glyceryl monostearate, glycerin monomyristate, glycerin monooleate , polyglycerin fatty acid esters include polyglyceryl monolaurate and silicone Examples of surfactants include polyoxyethylene-methylpolysiloxane copolymers, Lauryl PEG-9 Polydimethylsiloxyethyl Dimethicone, PEG-9 Polydimethylsiloxyethyl Dimethicone Examples include hydroxyethyl dimethicone.

[0057] Other surfactants include anionic surfactants and amphoteric surfactants. Examples of anionic surfactants include laurates, palmitates, and cocoyl Glutamate, coconut oil methylalanine salt, acylmethyltaurine salt, polyoxyethylene Examples of amphoteric surfactants include lauryl diaminoethylene. Examples include tetrglycine salt, coconut oil fatty acid betaine salt, etc.

[0058] The total amount of such surfactants is preferably 0.5 to 8 mass %, more preferably 1 to 5 % by mass, more preferably 1.5 to 4% by mass, and particularly preferably 1.6 to 3% by mass. They may be combined.

[0059] Thickeners include xanthan gum, sodium carboxymethylcellulose, and methylcellulose. cellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropyl Pillcellulose, hydroxypropyl methylcellulose, hydrophobized hydroxypropyl methylcellulose Examples of thickeners include polymers such as cellulose and carboxyvinyl polymer. is preferably 0.001 to 1 mass%, more preferably 0.05 to 0.5 mass%, and even more preferably Preferably, it may be blended at a ratio of 0.1 to 0.3 mass %.

[0060] Oils include natural animal and vegetable oils, hydrocarbon oils, ester oils, silicone oils, and alcohols. Examples of the oil include fatty acids, higher fatty acids, essential oils from animals, plants, and synthetic oils. 0.001 to 30% by mass, more preferably 1 to 20% by mass, and even more preferably 2 to 10% by mass %, or 3 to 5 mass %.

[0061] Examples of natural animal and vegetable oils include avocado oil, flaxseed oil, almond oil, and olive oil. Oil, cocoa oil, beef tallow, tung oil, wheat germ oil, sesame oil, rice germ oil, rice bran oil, safflower oil, Soybean oil, evening primrose oil, camellia oil, corn oil, rapeseed oil, horse fat, persic oil, palm Oil, palm kernel oil, castor oil, sunflower oil, lard, grape oil, jojoba oil, macadamia nuts Oil, mink oil, cottonseed oil, wax, beeswax, bleached beeswax, coconut oil, hardened coconut oil, Examples include flower oil, lanolin, egg yolk oil, and rosehip oil.

[0062] As the hydrocarbon oil, paraffin hydrocarbons and olefin hydrocarbons are used. For example, squalane, squalene, ceresin, paraffin, pristane, microcrystalline Examples of suitable waxes include paraffin wax, liquid paraffin, light liquid isoparaffin, and petrolatum.

[0063] Ester oils include synthetic esters and esters of higher alcohols and higher fatty acids. Examples of suitable esters include diisobutyl adipate, 2-hexyldecyl adipate, and adipic acid. Di-2-heptylundecyl isostearate, isostearyl isostearate, triisostearin Trimethylolpropane, Cetyl 2-ethylhexanoate, Di-2-ethylhexanoate Dipentyl glycol, trimethylolpropane tri-2-ethylhexanoate, tri(kaolin) Glyceryl Prillate / Caprate, Pentaerythritol Tetra-2-ethylhexanoate , Cetyl Octanoate, Oleyl Oleate, Octyldodecyl Oleate, Deoxy Oleate Sil, neopentyl glycol dicaprate, 2-ethylhexyl succinate, stearin Isocetyl ester, Butyl stearate, Diisopropyl sebacate, Cetyl lactate, Tetrasodium lactate Ladecyl, Isopropyl Myristate, Octyldodecyl Myristate, Ceteth-4 Myristate Myristyl myristate, isopropyl palmitate, octyl palmitate, palmitic acid 2-Ethylhexyl Palmitate, 2-Hexyldecyl Palmitate, 2-Hexyl Palmitate Butylundecyl, Cholesteryl 12-hydroxystearate, Phytosteryl Oleate Diisostearyl malate, para-methoxycinnamate, tetrarosinate pentaerythritol Examples include Taerithrit.

[0064] Examples of silicone oils include dimethicone, dimethylpolysiloxane, and highly polymerized methylsiloxane. Polysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane , Octamethylcyclotetrasiloxane, Octamethylcyclopentasiloxane, Decame Higher alkoxy-modified silicones such as ethylcyclohexasiloxane and stearoxy silicone Examples of the silicone include alkyl-modified silicone, higher fatty acid ester-modified silicone, and the like.

[0065] Examples of alcohols include lower alcohols and higher alcohols. As the alcohol, isopropanol is particularly preferred. As the higher alcohol, for example, For example, octyldodecanol, isostearyl alcohol, oleyl alcohol, myristyl alcohol alcohol, stearyl alcohol, cetanol, behenyl alcohol, etc. .

[0066] Higher fatty acids include saturated or unsaturated straight-chain or branched-chain fatty acids with 12 to 22 carbon atoms. Acids can be used, such as isostearic acid, oxystearic acid, oleic acid, Stearic acid, palmitic acid, behenic acid, myristic acid, lauric acid, lanolin acid, Examples include oleic acid and linolenic acid.

[0067] Moisturizing ingredients include hyaluronic acid (hydrolyzed hyaluronic acid, low molecular weight hyaluronic acid, etc.) hyaluronic acid salts (e.g., sodium hyaluronate, zinc hyaluronate, , low molecular weight zinc hyaluronate, etc.); hyaluronic acid derivatives (acetylated hyaluronic acid or its Salts (e.g., sodium acetylated hyaluronate, zinc acetylated hyaluronate, etc.), crosslinking agents Bridge-type hyaluronic acid derivatives (hyaluronic acid crosspolymer Na, etc.), carboxymethyl hyaluronic acid Sodium hyaluronate, unsaturated hyaluronic acid or its salt, hydrolyzed alkyl hyaluronate (C12 -13) Glyceryl, cationized hyaluronic acid derivative (hydroxypropyl hyaluronate) hydroxybenzoates, etc.), hyaluronic acid dimethylsilanol, etc.); chondroitin sulfate or its derivatives Salts (sodium chondroitin sulfate, potassium chondroitin sulfate, sodium dermatan sulfate) sodium, potassium dermatan sulfate, etc.); alanine, serine, aspartic acid, glycine, Glutamine, glutamic acid, proline, hydroxyproline, glucosamine, theanine, Amino acids such as arginine and their derivatives; glycerin, 1,2-propanediol, 1 ,3-propanediol, dipropylene glycol, 1,3-butanediol, diglycerides Phosphorus, pentylene glycol, polyethylene glycol, polypropylene glycol, etc. Polyhydric alcohols: sorbitol, xylitol, erythritol, maltose, sucrose sugar alcohols such as condensates (glucooligosaccharides) and hydrolyzed xylans (xylooligosaccharides); PPG-17 Buteth-17, PPG-25 Sorbitol, Polyoxyalkylene Alkyl Glucoside, PEG / PPG / Polybutylene Glycol-8 / 5 / 3 Glycerin, Polio Alkylene oxides such as hydroxyalkylene diglycerides; glycosyl trehalose, trehalose Haloth; ceramide, pseudoceramide, glucosylceramide, cholesterol, phytosterol chol, cholesterol derivatives, phytosterol derivatives; lecithin, hydrogenated lecithin Phospholipids such as 2-methacryloyloxyethyl phosphorylcholine·butyric acid methyl ester Copolymer liquid, 2-methacryloyl such as polymethacryloyloxyethyl phosphorylcholine Oxyphosphorylcholine-containing polymer; lactic acid, sodium lactate, sodium pyrrolidone carboxylate NMF-derived components such as sodium and urea; collagen, elastin, keratin, chitin, chitosan San and their hydrolysates; hydroxyethyl urea; plants (e.g., aloe, seaweed) , Pueraria lobata, chlorella, lemongrass, chamomile, hamamelis, tea, perilla, grapefruit Roots, Gynostemma pentaphyllum, etc.

[0068] Antioxidants include dibutylhydroxytoluene (BHT), butylhydroxyaniline Sole (BHA), sodium sulfite, erythorbic acid, L-cysteine ​​hydrochloride, vitamin Vitamin C compounds include, for example, ascorbigen-A, ascorbic acid, Ascorbic acid stearate, ascorbic acid palmitate, dipalmitic acid L-ascorbyl, ascorbic acid, sodium ascorbate, dehydroascorbic acid Acid, Sodium Ascorbyl Phosphate, Sodium Ascorbyl Phosphate, Magnesium scorbic acid phosphate.

[0069] Cooling agents include, but are not limited to, menthol (l-menthol, dl-menthol) camphor (d-camphor, dl-camphor, etc.), terpenes such as borneol essential oils (mentha oil) containing terpenoids, or pharmacologically acceptable salts thereof, etc. One or more of these drugs may be used in combination as appropriate. Cut.

[0070] Preservatives include benzoic acid, sodium benzoate, acetic acid, dehydroacetic acid, and dehydroacetic acid. Sodium, isobutyl parahydroxybenzoate, isopropyl parahydroxybenzoate, Palau Butyl parahydroxybenzoate, Ethyl parahydroxybenzoate, Propyl parahydroxybenzoate, Palau Benzyl parahydroxybenzoate, methyl parahydroxybenzoate, phenol, phenoxyethanol , phenethyl alcohol, benzyl alcohol, tincture of iodine, chlorobutanol, etc. Examples include:

[0071] Chelating agents include ethylenediaminetetraacetic acid (edetic acid), ethylenediaminetetraacetic acid Salts (sodium salts (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium Examples include phosphate salts, phytic acid, gluconic acid, polyphosphoric acid, and metaphosphoric acid. , sodium edetate is preferred.

[0072] pH adjusters include inorganic acids (hydrochloric acid, sulfuric acid, etc.), organic acids (lactic acid, sodium lactate, Citric acid, sodium citrate, succinic acid, sodium succinate, disodium succinate, etc. etc.), inorganic bases (potassium hydroxide, sodium hydroxide, etc.), organic bases (triethanolamine, etc.) Amines, diisopropanolamine, triisopropanolamine, basic amino acids, etc. ) Basic amino acids include lysine, histidine, and arginine. can be done.

[0073] Examples of buffering agents include phosphate, acetate, carbonate, and citrate buffer solutions. It can be obtained.

[0074] Examples of colorants include inorganic pigments and natural dyes.

[0075] The liquid composition for external use of the present invention may further contain other effective ingredients within the range that does not impair the effects of the present invention. Specific examples of such ingredients include moisturizing ingredients, blood circulation promoting ingredients, and the like. Active ingredients, astringent ingredients, peptides or their derivatives, amino acids or their derivatives, cell activating ingredients , vitamin supplements, etc.

[0076] [pH] The pH of the liquid composition for external use of the present invention depends on the type of component (A) and the types and contents of other ingredients. The dosage is determined appropriately depending on the formulation, method of use, etc., and is within a physiologically or pharmaceutically acceptable range. There are no limitations as long as the pH is within the range of 2 to 9, but from the viewpoint of safety, the pH may be, for example, 2 to 9, and is preferred. Preferably, it can be about 3 to 8, and more preferably about 5 to 7.

[0077] [viscosity] The viscosity of the liquid composition for external application of the present invention is determined based on the total amount of the liquid composition for external application from the viewpoint of ease of handling of the preparation. , preferably 100 mPa·s to 10 Pa·s, and more preferably 1 Pa·s s to 8 Pa·s, and more preferably 3 Pa·s to 6 Pa·s. The viscosity is measured using a RB80 viscometer manufactured by Toki Sangyo Co., Ltd., with an M3 rotor at a rotation speed of 12r pm, and the results obtained when measuring for 1 minute.

[0078] [Application] The liquid composition for external use of the present invention is a liquid composition for external use that is applied in the form of a foam. The liquid composition for use is not limited, but is preferably applied to the skin, particularly to a large area, so that the composition can be spread This is because the foam is easy to handle and is suitable for use on areas of the skin that need to be spread evenly. Such skin sites are preferably the lower limbs, upper limbs, the posterior trunk, the anterior trunk, More preferred are the arms, legs, back, abdomen, buttocks, and décolleté. It is especially suitable for delicate skin, such as those with the following conditions or sensitive skin: This is because the liquid composition of the present invention is in foam form and can be applied to the affected area without touching it strongly. The liquid composition for external application of the present invention is effective in treating dry skin symptoms. Used for the treatment, prevention, or alleviation of symptoms caused by circulatory disorders For example, dry skin conditions such as itchy skin diseases, senile xerosis, atopic dermatitis, and housewives' eczema. Skin diseases, inflammatory skin diseases, itching, razor burn, heat rash, chilblains, cracks, Based on chapped skin, sebum deficiency, progressive digital palmar keratoderma, chilblains, hypertrophic scars / keloids, and blood circulation disorders. Pain or inflammatory diseases, thrombophlebitis, lumps and stiffness after trauma (bruises, sprains, contusions) It is used to treat, prevent, or relieve swelling, hematoma, tendonitis, muscle pain, arthritis, etc.

[0079] The method of using the liquid composition for external use of the present invention can be varied depending on the condition of the affected area of ​​the skin, age, sex, etc. Although the dosage may vary depending on the individual, the following method may be used, for example: 5 times, preferably 1 to 3 times, more preferably 1 time), and a suitable amount (for example, about 0.5 times) of foam. Apply approximately 2g to the affected area.

[0080] [How to create stretchy foam] The present invention also provides (A) a heparinoid; and (B) glycyrrhetinic acid, ... Derivatives of luretic acid and / or their salts, allantoin, tocopherol acetate, maleic anhydride Chlorpheniramine dihydrochloride, diphenhydramine and / or its salts, lidocaine and / or is selected from the group consisting of dibucaine and / or its salts, and crotamiton A method for forming foam with good spreadability by using a compound containing one or more compounds; Preferably, such foam is also soft and highly adhesive. The concentration of each component in the liquid composition for external use of the present invention is The same conditions as those of the formulation, such as pH, etc., are used. [Example]

[0081] Next, the present invention will be specifically described with reference to examples and test examples. It is not limited to the examples.

[0082] The ingredients listed in Table 1 were mixed in the aqueous phase and the oil phase, respectively, and prepared in a conventional manner to prepare an external liquid. A composition was obtained. Next, the composition and liquefied petroleum gas (LPG) were mixed in a foam-discharging aerosol container in a mass ratio of 1:1. It was filled in a ratio of 92:8.

[0083] [Test Example 1. Bubble Drop Evaluation Test 1] At 25°C and a relative humidity of 50±5%, the compositions of the examples and comparative examples were applied to artificial leather in 0.5 ml of water. Then, the artificial leather was fixed vertically on the laboratory bench. The moment when the leather (Idemitsu Technofine Co., Ltd., product number: PBZ13001) was stood upright was recorded at 0 seconds. After a certain period of time, the distance the bubbles traveled (the bubbles falling due to gravity) was measured. Depending on the formulation, some of the foam may collapse and drip as liquid, but the largest The position of the bottom of the foam is set to 0 cm, and the difference between this and the position of the bottom of the foam after a certain time is the distance The evaluation results are shown in Table 2.

[0084] [Test Example 2. Evaluation test for foam firmness] At 25°C and a relative humidity of 50±5%, a 10 mL glass beaker (bottom diameter 3.0 mm) was 1.5 g of the compositions of the Examples and Comparative Examples was sprayed onto the surface of the skin. After about 15 seconds had passed since the spraying, Place a 10 yen coin on top of this and make sure one side of the coin is completely in contact with the bottom of the beaker. The time until the water reached the bottom, i.e., the time until the water completely sank, was measured. The evaluation results are shown in Table 3.

[0085] [Test Example 3. Bubble Drop Evaluation Test 2] At 25°C and a relative humidity of 50±5%, the compositions of the examples and comparative examples were applied to the artificial leather for 1 minute. Next, the artificial leather was turned over so that the surface not sprayed with the composition was facing upward. The upper surface was fixed. The moment it was fixed was set to 0 seconds, and the time it took for the largest foam to fall was measured. As a result, the compositions of Examples 1 to 5 did not fall off for 20 minutes or more.

[0086] [Table 1]

[0087] [Table 2]

[0088] [Table 3]

[0089] From the results of Test Examples 1 and 2, it can be seen that the foam formed by the compositions of the Examples is comparable to that of the compositions of the Comparative Examples. It is easier for the object to move vertically downwards due to gravity than the 10-yen coin, and it collapses due to the gravity of the 10-yen coin. In other words, the foam formed by the composition of the example can be easily formed with a weak force. I found it to be easy to crush and stretchy.

[0090] Test Example 3 shows that the foam formed by the composition of the example has good spreadability compared to Test Example 1. Although this has been demonstrated, it was found that the bubbles were difficult to fall. It was found that the foam formed by the composition of 5 had high adhesion.

[0091] Formulation examples of the present invention are shown below. Liquid compositions for external use were prepared by a conventional method using the formulations shown in Table 4. All formulation examples are prepared in a container to form foam. Formulation Examples 1 to 9 The formulations are all packaged in a pump foamer container and a foam-discharging aerosol container containing a propellant. are housed in the following areas:

[0092] [Table 4]

Claims

1. (A) 0.01 to 0.5% by mass of a heparinoid; and (B) 0.2 to 10% by mass of one or more compounds selected from the group consisting of glycyrrhetinic acid and / or a salt thereof, glycyrrhizinic acid and / or a salt thereof, allantoin, tocopherol acetate, chlorpheniramine maleate, diphenhydramine and / or a salt thereof, lidocaine and / or a salt thereof, dibucaine and / or a salt thereof, and crotamiton; and water and contained in an aerosol foam-discharging container containing a propellant (excluding, however, (1) a composition for external use on skin that contains (A) a heparinoid and (B) vitamin B6 and has a pH of 4 or higher; and (2) an aerosol composition that contains polyoxyethylene sterol, a solvent, and a propellant).

2. 2. The liquid composition for external use according to claim 1, wherein the mass ratio of the liquid composition for external use to the propellant is 50:50 to 99:

1.

3. 3. The liquid composition for external use according to claim 1, wherein the ratio of component (B) to component (A) is 0.3 to 35 parts by mass per 1 part by mass of the content of component (A).

4. (A) 0.01 to 0.5% by mass of a heparinoid; and A method for forming a spreadable foam by containing 0.2 to 10% by mass of (B) one or more compounds selected from the group consisting of glycyrrhetinic acid and / or a salt thereof, glycyrrhetinic acid and / or a salt thereof, allantoin, tocopherol acetate, chlorpheniramine maleate, diphenhydramine and / or a salt thereof, lidocaine and / or a salt thereof, dibucaine and / or a salt thereof, and crotamiton; and water in a composition, filling the composition into an aerosol foam-dispensing container containing a propellant, and applying the composition (excluding, however, cases in which the composition is an aerosol composition characterized by containing (1) a composition for external use on skin containing (A) a heparinoid and (B) vitamin B6 and having a pH of 4 or higher; and (2) a polyoxyethylene sterol, a solvent, and a propellant).

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