Topical liquid composition for bubble application

Abstract

To provide an external liquid composition that contains a heparin analog and has a good feeling in use.SOLUTION: An external liquid composition is prepared that contains (A) a heparin analog, and (B) at least one compound selected from the group consisting of glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or salts thereof, allantoin, tocopherol acetate, chlorpheniramine maleate, diphenhydramine and / or salts thereof, lidocaine and / or salts thereof, dibucaine and / or salts thereof, and crotamiton. The external liquid composition is applied in foamy state.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an external liquid composition for foamy application. More specifically, it relates to an external liquid composition containing a heparin-like substance and being foamy upon application.

Background Art

[0002] Heparin-like substances have a moisturizing effect and an anti-inflammatory effect and are widely used in pharmaceuticals. Due to the skin moisturizing effect of heparin-like substances, dry skin symptoms are alleviated. Also, due to the blood circulation promoting effect of heparin-like substances, blood circulation at the application site is promoted, and pain and swelling due to blood circulation disorders are alleviated.

[0003] For example, Patent Document 1 discloses a skin external liquid composition containing vitamin A compounds, edetic acid or its salt, and a heparin-like substance. And according to this skin external liquid composition, it is described that vitamin A compounds can be stably contained.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] Although heparin-like substances are considered to be usable on rough skin or delicate areas, there is not enough knowledge regarding the usability of a foamy external liquid composition containing heparin-like substances.

[0006] The present invention has been made in view of the above, and an object thereof is to provide an external liquid composition for foamy application containing a heparin-like substance and having good usability.

Means for Solving the Problems

[0007] Vesicular topical agents are known for their unique and excellent softness and ease of handling, which are different from creams and liquids. On the other hand, regarding the properties of bubbles containing components having effects such as heparin-like substances, detailed studies are necessary.

[0008] An object of the present invention is to provide a topical liquid composition in the form of a foam that has an excellent feel in use. The present inventors have found that by containing (A) a heparin-like substance and (B) one or more compounds selected from the group consisting of glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or their salts, allantoin, tocopherol acetate, chlorpheniramine maleate, diphenhydramine and / or its salt, lidocaine and / or its salt, dibucaine and / or its salt, and chlorotrimeton, a topical liquid composition capable of providing bubbles with good expansion when applied in the form of a foam can be obtained, and thus the present invention has been completed.

[0009] That is, the present invention provides the following topical liquid composition. Item 1. (A) A heparin-like substance; and (B) One or more compounds selected from the group consisting of glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or their salts, allantoin, tocopherol acetate, chlorpheniramine maleate, diphenhydramine and / or its salt, lidocaine and / or its salt, dibucaine and / or its salt, and chlorotrimeton; A topical liquid composition containing the same and housed in a foam discharge container. Item 2. The topical liquid composition according to Item 1, wherein the foam discharge container is an aerosol container containing a propellant. Item 3. (A) A heparin-like substance; and (B) 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 and / or salts thereof, lidocaine and / or salts thereof, dibucaine and / or salts thereof, and chlorothen; An external liquid composition for being applied in a foamy state and containing the same. Item 4. The external liquid composition according to item 3, wherein the foam is formed by an aerosol container for discharging foam containing a propellant. Item 5. The external liquid composition according to item 2 or 4, wherein the mass ratio of the external liquid composition to the propellant is 50:50 to 99:1. Item 6. The external liquid composition according to any one of items 1 to 5, further containing ethanol.

[0010] The present invention also provides the following method. Item 7. (A) Heparin-like substances; and (B) 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 and / or salts thereof, lidocaine and / or salts thereof, dibucaine and / or salts thereof, and chlorothen; A method for forming well-expanded foam by coexisting the same.

Advantages of the Invention

[0011] According to the present invention, it is possible to provide an external liquid composition for being applied in a well-expanded foamy state.

Embodiments for Carrying Out the Invention

[0012] [External Liquid Composition] The present invention relates to (A) heparin-like substances; and (B) 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 and / or salts thereof, lidocaine and / or salts thereof, dibucaine and / or salts thereof, and chlorotrimeton; It relates to an external liquid composition containing the same and housed in a foam discharge container.

[0013] The present invention further relates to (A) a heparin analogue; and (B) 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 and / or salts thereof, lidocaine and / or salts thereof, dibucaine and / or salts thereof, and chlorotrimeton; It relates to an external liquid composition for foamy application containing the same.

[0014] ((A) Heparin analogue) A heparin analogue is a substance called mucopolysaccharide polysulfate ester or heparinoid, which is obtained by introducing a large amount of sulfate groups into a mucopolysaccharide having a repeating structure of disaccharide composed of D-glucuronic acid and N-acetyl-D-galactosamine. As the heparin analogue, the heparin analogue described in the Japanese Pharmaceutical Excipients Standard is preferred.

[0015] The amount (%) of the organic sulfate group in the heparin analogue is not particularly limited, but from the viewpoint of drug effects such as a moisturizing effect, 25 to 38% is preferred. The amount of the organic sulfate group can be measured, for example, by the method described in the section of "Heparin analogue" in the Japanese Pharmaceutical Excipients Standard.

[0016] (A) The content of the heparin-like substance is preferably 0.001% by mass or more, more preferably 0.01% by mass or more, still more preferably 0.1% by mass or more, even more preferably 0.2% by mass or more, and particularly preferably 0.3% by mass or more, based on the total amount of the external liquid composition, from the viewpoint of more significantly exhibiting the effects of the present invention. The total content of the (A) heparin-like substance is preferably 1% by mass or less, more preferably 0.5% by mass or less, and still more preferably 0.3% by mass or less, based on the total amount of the external liquid composition, from the viewpoint of more significantly exhibiting the effects of the present invention. The content of the (A) heparin-like substance is preferably 0.001% by mass to 1% by mass, more preferably 0.01% by mass to 0.5% by mass, still more preferably 0.1% by mass to 0.3% by mass, and particularly preferably 0.2% by mass to 0.3% by mass, based on the total amount of the external liquid composition, from the viewpoint of more significantly exhibiting the effects of the present invention. Among them, 0.3% by mass is most preferable.

[0017] ((B) 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 and / or salts thereof, lidocaine and / or salts thereof, dibucaine and / or salts thereof, and chlorotrimeton) As the component (B) of the present invention, the following substances can be used, and there is no particular limitation as long as they are these. That is, 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 and / or salts thereof, lidocaine and / or salts thereof, dibucaine and / or salts thereof, and chlorotrimeton.

[0018] ((B-1) Glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and / or salts thereof) The glycyrrhetinic acid or its derivative used in the present invention is not particularly limited as long as it is a grade used in pharmaceuticals, quasi-drugs, cosmetics, etc. As the salt of glycyrrhetinic acid or its derivative, any pharmacologically acceptable salt may be used, for example, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; salts with amines such as tilamine, triethylamine, triethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, etc. Examples of the derivative of glycyrrhetinic acid include glycosides of glycyrrhetinic acid, and among them, glycyrrhizic acid is particularly mentioned. Among these, glycyrrhizic acid, alkali metal salts of glycyrrhizic acid, and more preferably dipotassium glycyrrhizinate are particularly preferred. One kind of glycyrrhetinic acid, its derivative, and / or their salts may be used alone, or two or more kinds may be used in combination.

[0019] ((B-2) Allantoin) The allantoin used in the present invention is not particularly limited as long as it is a grade used in pharmaceuticals, quasi-drugs, cosmetics, etc.

[0020] ((B-3) Tocopherol acetate) The tocopherol acetate used in the present invention is not particularly limited as long as it is a grade used in pharmaceuticals, quasi-drugs, cosmetics, etc.

[0021] ((B-4) Chlorpheniramine maleate) The chlorpheniramine maleate used in the present invention is not particularly limited as long as it is a grade used in pharmaceuticals, quasi-drugs, cosmetics, etc.

[0022] ((B-5) Diphenhydramine and / or its salt) The diphenhydramine used in the present invention is not particularly limited as long as it is a grade used in pharmaceuticals, quasi-drugs, cosmetics, etc. As the salt of diphenhydramine, any pharmacologically acceptable salt may be used. Examples include acid addition salts such as hydrochloride, citrate, succinate, tartrate, fumarate, maleate, salicylate, diphenyldisulfonate, tannate, lauryl sulfate, and sulfate. Among these, diphenhydramine hydrochloride is preferred. One kind of diphenhydramine and / or its salt may be used alone, or two or more kinds 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 not particularly limited as long as it is a grade used in pharmaceuticals, quasi-drugs, cosmetics, etc. As the salt of lidocaine or dibucaine, any pharmacologically acceptable salt may be used. Examples include acid addition salts such as hydrochloride, citrate, succinate, tartrate, fumarate, maleate, salicylate, diphenyldisulfonate, tannate, lauryl sulfate, and sulfate. Among these, lidocaine hydrochloride and dibucaine hydrochloride are preferred. One kind of lidocaine and / or its salt, dibucaine and / or its salt may be used alone, or two or more kinds may be used in combination.

[0024] ((B-8) chlorothen) The chlorothen used in the present invention is not particularly limited as long as it is a grade used in pharmaceuticals, quasi-drugs, cosmetics, etc.

[0025] From the viewpoint of more significantly exerting the effects of the present invention, the total content of component (B) is preferably 0.2% by mass or more, more preferably 0.5% by mass or more, still more preferably 0.7% by mass or more, and particularly preferably 1.2% by mass or more, based on the total amount of the external liquid composition. From the viewpoint of more significantly exerting the effects of the present invention, the total content of component (B) is preferably 10% by weight or less, more preferably 6% by weight or less, still more preferably 3% by weight or less, and particularly preferably 1.7% by mass or less, based on the total amount of the external liquid composition. From the viewpoint of more significantly exerting the effects of the present invention, the total content of component (B) is preferably 0.2% by mass to 10% by mass, more preferably 0.5% by mass to 6% by mass, still more preferably 0.7% by mass to 3% by mass, and particularly preferably 1.2% by mass to 1.7% by mass, based on the total amount of the external liquid composition.

[0026] In the external liquid composition of the present invention, from the viewpoint of more significantly exerting the effects according to the present invention, the ratio of the total amount of component (B) to component (A) is, for example, preferably 0.3 part by mass or more, more preferably 1 part by mass or more, still more preferably 2 parts by mass or more, even more preferably 3 parts by mass or more, and particularly preferably 5 parts by mass or more, based on 1 part by mass of the content of component (A). From the viewpoint of more significantly exerting the effects of the present invention, the total content of component (B) is preferably 35 parts by mass or less, more preferably 25 parts by mass or less, still more preferably 15 parts by mass or less, and particularly preferably parts by mass or less, based on 1 part by mass of the content of component (A). In the external liquid composition of the present invention, the ratio of component (B) to component (A) is, for example, preferably 0.3 to 35 parts by mass, more preferably 1 to 25 parts by mass, even more preferably 2 to 15 parts by mass, and particularly preferably 3 to 7 parts by mass, based on 1 part by mass of the content of component (A).

[0027] When the component (B) contains glycyrrhetinic acid, a derivative of glycyrrhetinic acid, and / or a salt thereof, from the viewpoint of remarkably exhibiting the effects of the present invention, the content of glycyrrhetinic acid, a derivative of glycyrrhetinic acid, and / or a salt thereof is 0.05% by mass to 1% by mass, more preferably 0.1% by mass to 0.5% by mass, and still more preferably 0.3% by mass to 0.5% by mass with respect to the total amount of the external liquid composition.

[0028] In the external liquid composition of the present invention, the ratio of the component (B-1) to the component (A) is, for example, preferably 0.1 to 4 parts by mass, more preferably 0.5 to 4 parts by mass, still more preferably 1 to 4 parts by mass, and particularly preferably 1.5 to 3.5 parts by mass with respect to 1 part by mass of the content of the component (A).

[0029] For example, when the component (B) contains allantoin (B-2), from the viewpoint of remarkably exhibiting the effects of the present invention, the content of allantoin is preferably 0.02% by mass to 0.2% by mass, more preferably 0.05% by mass to 0.2% by mass, and still more preferably 0.1% by mass to 0.2% by mass with respect to the total amount of the external liquid composition.

[0030] In the external liquid composition of the present invention, the ratio of the component (B-2) to the component (A) is, for example, preferably 0.01 to 2 parts by mass, more preferably 0.1 to 2 parts by mass, still more preferably 0.2 to 1 part by mass, and particularly preferably 0.5 to 0.7 part by mass with respect to 1 part by mass of the content of the component (A).

[0031] For example, when the component (B) contains tocopherol acetate (B-3), from the viewpoint of remarkably exhibiting the effects of the present invention, the content of tocopherol acetate is preferably 0.001% by mass to 0.5% by mass, more preferably 0.05% by mass to 0.5% by mass, still more preferably 0.1% by mass to 0.5% by mass, and particularly preferably 0.27% by mass to 0.5% by mass with respect to the total amount of the external liquid composition.

[0032] In the external liquid composition of the present invention, the ratio of the component (B-3) to the component (A) is preferably, for example, 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, even more preferably 0.5 to 3.5 parts by mass, and particularly preferably 1.5 to 2 parts by mass with respect to 1 part by mass of the content of the component (A).

[0033] For example, when the component (B) contains (B-4) chlorpheniramine maleate, from the viewpoint of significantly exhibiting the effects of the present invention, the content of chlorpheniramine maleate is preferably 0.2% by mass to 2% by mass, and more preferably 0.5% by mass to 1% by mass.

[0034] In the external liquid composition of the present invention, the ratio of the component (B-4) to the component (A) is preferably, for example, 1 to 4 parts by mass, and more preferably 2 to 4 parts by mass with respect to 1 part by mass of the content of the component (A).

[0035] For example, when the component (B) contains (B-5) diphenhydramine and / or its salt, from the viewpoint of significantly exhibiting the effects of the present invention, the content of diphenhydramine and / or its salt is preferably 0.2% by mass to 2% by mass, and more preferably 0.5% by mass to 1% by mass with respect to the total amount of the external liquid composition.

[0036] In the external liquid composition of the present invention, the ratio of the component (B-5) to the component (A) is preferably, for example, 1 to 4 parts by mass, and more preferably 2 to 4 parts by mass with respect to 1 part by mass of the content of the component (A).

[0037] For example, when the component (B) contains (B-6) lidocaine and / or its salt, from the viewpoint of significantly exhibiting the effects of the present invention, the content of lidocaine and / or its salt is preferably 0.2% by mass to 2% by mass, and more preferably 1% by mass to 2% by mass.

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

[0039] For example, when the component (B) contains (B-7) dibucaine and / or a salt thereof, from the viewpoint of remarkably exhibiting the effects of the present invention, the content of dibucaine and / or a salt thereof is preferably 0.2% by mass to 2% by mass, more preferably 1% by mass to 2% by mass.

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

[0041] For example, when the component (B) contains (B-8) chlorpheniramine, from the viewpoint of remarkably exhibiting the effects of the present invention, the content of chlorpheniramine is preferably 2% by mass to 10% by mass, more preferably 2% by mass to 5% by mass with respect to the total amount of the external liquid composition.

[0042] In the external liquid composition of the present invention, the ratio of the component (B-8) to the component (A) is, for example, preferably 5 to 40 parts by mass, more preferably 10 to 20 parts by mass with respect to 1 part by mass of the content of the component (A).

[0043] (Ethanol) In the present invention, in addition to the (A) heparin-like substance and the above-mentioned component (B), any known component that can be used as a pharmaceutical, quasi-drug, cosmetic, etc. can be contained in the external liquid composition as long as its function is not impaired. As the optional component, it is particularly preferable to be able to contain ethanol.

[0044] The ethanol used in the external liquid composition of the present invention is not particularly limited as long as it is a grade or grade used in pharmaceuticals, quasi-drugs, cosmetics, etc. As the ethanol used as a raw material for the external liquid composition, for example, 95% ethanol, 99% ethanol (anhydrous ethanol), etc. can be appropriately used.

[0045] From the viewpoints of foam formation and feel in use, the ethanol content is preferably more than 0% by mass, more preferably 0.01% by mass or more, and still more preferably 0.1% by mass or more, based on the total amount of the external liquid composition. From the viewpoints of foam formation and feel in use, the ethanol content is preferably 5% by mass or less, more preferably 3% by mass or less, and still more preferably 1% by mass or less, based on the total amount of the external liquid composition. Based on the total amount of the external liquid composition, the ethanol content is preferably 0.01 to 3% by mass, and more preferably 0.1 to 1% by mass.

[0046] In the external liquid composition of the present invention, from the viewpoint of feel in use, the ratio of ethanol to the component (A) is, for example, preferably 0.033 to 17 parts by mass, and more preferably 0.33 to 10 parts by mass of ethanol content with respect to 1 part by mass of the content of the component (A).

[0047] [Container] The external liquid composition of the present invention is preferably contained in a foam discharge container.

[0048] Here, the foam discharge container is preferably a pump foamer container or a foam discharge aerosol container containing a propellant, and more preferably a foam discharge aerosol container containing a propellant. That is, a foaming aerosol container that enables a mode of filling the external liquid composition together with a propellant into a container and applying the foam formed after ejection from the container to the skin is particularly preferable. Here, as the propellant, carbon dioxide (carbon dioxide gas), nitrogen, liquefied petroleum gas (LPG), or dimethyl ether (DME) is preferably used.

[0049] The material of the container for filling the external liquid composition of the present invention is not particularly limited. Any material can be used as long as it is used as a container for external pharmaceutical agents, quasi-drugs, and cosmetics. As the container material of the pump former, for example, part or all of the contact surface with the external liquid composition, preferably all, is made of at least one material selected from the group consisting of polyolefin resin, acrylic resin, polyester, polycarbonate, fluororesin, polyvinyl chloride, polyamide, ABS resin, AS resin, polyacetal, modified polyphenylene ether, polyarylate, polysulfone, polyimide, cellulose acetate, aluminum, and glass.

[0050] As the material of the aerosol container for discharging foam containing a propellant, for example, metal containers such as aluminum, steel, or tinplate can be mentioned. The inner surface of the metal container may be coated with an epoxy resin, a phenol resin, a polyamideimide resin, or the like.

[0051] Here, when using a foam discharge container containing a propellant, although not limited, preferably, the mass ratio of the external 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 still more preferably 92:8 to 93:7, and it is preferably filled in the container.

[0052] [Dosage form] The external liquid composition of the present invention is a liquid that can be used as a pharmaceutical, a quasi-drug, etc., and is not limited as long as it is a liquid capable of forming foam, but is usually provided in the form of an aqueous composition. Here, the aqueous composition refers to a dosage form in which the ratio of water or a water-soluble solvent in the total amount of the composition is 10% by mass or more, and preferably 50% by mass or more, more preferably 70% by mass or more, from the viewpoints of the stability of the preparation or the feeling of use.

[0053] The preparation can be produced by mixing each component in accordance with or in accordance with the General Rules of the 17th Revision of the Japanese Pharmacopoeia.

[0054] [Production method] The external liquid composition of the present invention can be produced by a known method. If necessary, a sterilization step or a filtration step can be included.

[0055] [Base, carrier, or other component] The external liquid composition of the present invention can be formulated by mixing known components that can be used as pharmaceuticals, quasi-drugs, cosmetics, etc. within a range that does not impair the effects of the present invention. Known components include, for example, additives such as surfactants, thickeners, oils, moisturizing components, preservatives, antioxidants, cooling agents, chelating agents, pH adjusters, buffers, fragrances, coloring agents, and pigments. These additives can be used alone or in combination of two or more.

[0056] Examples of the surfactant include, for example, nonionic surfactants. Examples of the nonionic surfactants include, for example, sorbitan fatty acid esters, propylene glycol fatty acid esters, castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyalkylene alkyl ethers, glycerin fatty acid esters, polyglycerin fatty acid esters, silicone-based surfactants, polyoxyethylene lauryl alcohol ethers and the like.Examples of sorbitan fatty acid esters include sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, diglycerol sorbitan penta-2-ethylhexanoate, diglycerol sorbitan tetra-2-ethylhexanoate, sorbitan sesquioleate, etc. Examples of propylene glycol fatty acid esters include propylene glycol fatty acid esters such as propylene glycol monostearate. Examples of castor oil derivatives include polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, etc. Examples of polyoxyethylene sorbitan fatty acid esters include polyoxyethylene(20)sorbitan monolaurate (polysorbate 20), polyoxyethylene(20)sorbitan monostearate (polysorbate 60), polyoxyethylene(20)sorbitan monooleate (polysorbate 80), polyoxyethylene(20)sorbitan isostearate, etc. Examples of polyoxyalkylene alkyl ethers include polyoxyethylene glyceryl monolaurate, glycerin alkyl ether, alkyl glucoside, polyoxyethylene cetyl ether, polyoxyethylene lauryl ether, polyoxyethylene monostearate, polyoxyethylene monooleate, polyoxyethylene monolaurate, etc. Examples of glycerin fatty acid esters include glyceryl monostearate, glyceryl monomyristate, glyceryl monooleate. Examples of polyglycerin fatty acid esters include polyglyceryl monolaurate. Examples of silicone-based surfactants include polyoxyethylene·methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, PEG-9 polydimethylsiloxyethyl dimethicone, etc.

[0057] Other surfactants include anionic surfactants, amphoteric surfactants, etc. Examples of anionic surfactants include laurates, palmitates, cocoyl glutamates, coconut oil methyl alanine salts, acyl methyl taurine salts, polyoxyethylene lauryl sulfates, etc. Examples of amphoteric surfactants include lauryldiaminoethyl glycine salts, coconut oil fatty acid betaine salts, etc.

[0058] The total amount of such surfactants may preferably be blended at a ratio of 0.5 to 8% by mass, more preferably 1 to 5% by mass, still more preferably 1.5 to 4% by mass, and particularly preferably 1.6 to 3% by mass.

[0059] Examples of thickeners include polymers such as xanthan gum, sodium carboxymethyl cellulose, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydrophobized hydroxypropyl methyl cellulose, and carboxyvinyl polymer. The amount of the thickener may preferably be blended at a ratio of 0.001 to 1% by mass, more preferably 0.05 to 0.5% by mass, and still more preferably 0.1 to 0.3% by mass.

[0060] Examples of the oil component include natural animal and vegetable oils and fats, hydrocarbon oils, ester oils, silicone oils, alcohols, higher fatty acids, essential oils of animals, plants, and synthetic materials, etc. The amount of the oil component may preferably be blended at a ratio of 0.001 to 30% by mass, more preferably 1 to 20% by mass, still more preferably 2 to 10% by mass, and 3 to 5% by mass.

[0061] Examples of natural animal and vegetable oils and fats include avocado oil, linseed oil, almond oil, olive oil, cocoa butter, beef tallow, candlenut 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 seed oil, jojoba oil, macadamia nut oil, mink oil, cottonseed oil, beeswax, candelilla wax, carnauba wax, coconut oil, hydrogenated coconut oil, peanut oil, lanolin, egg yolk oil, rose hip oil, etc.

[0062] As hydrocarbon oils, paraffinic hydrocarbons and olefinic hydrocarbons are used. Examples include squalane, squalene, ceresin, paraffin, pristane, microcrystalline wax, liquid paraffin, light liquid isoparaffin, petrolatum, etc.

[0063] As ester oils, synthetic esters and esters of higher alcohols and higher fatty acids are used. Examples include diisobutyl adipate, 2-hexyldecyl adipate, di-2-heptylundecyl adipate, isostearyl isostearate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, neopentyl glycol di-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, glyceryl tri(caprylate / caprate), pentaerythritol tetra-2-ethylhexanoate, cetyl octanoate, oleyl oleate, octyldodecyl oleate, decyl oleate, neopentyl glycol dicaprate, 2-ethylhexyl succinate, isocetyl stearate, butyl stearate, diisopropyl sebacate, cetyl lactate, tetradecyl lactate, isopropyl myristate, octyldodecyl myristate, cetyl myristate, myristyl myristate, isopropyl palmitate, octyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, 2-heptylundecyl palmitate, cholesteryl 12-hydroxystearate, phytosteryl oleate, diisostearyl malate, paramethoxycinnamic acid ester, pentaerythrityl tetraricinoleate, etc.

[0064] Examples of silicone oils include dimethicone, dimethylpolysiloxane, highly polymerized methylpolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, octamethylcyclotetrasiloxane, octamethylcyclopentasiloxane, decamethylcyclohexasiloxane, and higher alkoxy-modified silicones such as stearoxysilicone, alkyl-modified silicones, and higher fatty acid ester-modified silicones.

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

[0066] As the higher fatty acid, a saturated or unsaturated straight-chain or branched-chain fatty acid having 12 to 22 carbon atoms can be used. Examples include isostearic acid, oxystearic acid, oleic acid, stearic acid, palmitic acid, behenic acid, myristic acid, lauric acid, lanolinic acid, linoleic acid, and linolenic acid.

[0067] Examples of moisturizing ingredients include, for example, hyaluronic acid (including hydrolyzed hyaluronic acid, low-molecular-weight hyaluronic acid, etc.); salts of hyaluronic acid (e.g., sodium hyaluronate, zinc hyaluronate, low-molecular-weight zinc hyaluronate, etc.); hyaluronic acid derivatives (acetyl hyaluronic acid or its salts (e.g., sodium acetyl hyaluronate, zinc acetyl hyaluronate, etc.), cross-linked hyaluronic acid derivatives (e.g., sodium hyaluronic acid cross-polymer, etc.), sodium carboxymethyl hyaluronic acid, unsaturated hyaluronic acid or its salts, alkyl (C12-13) glyceryl hydrolyzed hyaluronic acid, cationized hyaluronic acid derivatives (e.g., hydroxypropyltrimonium hyaluronate, etc.), dimethylsilanol hyaluronic acid, etc.); chondroitin sulfate or its salts (sodium chondroitin sulfate, potassium chondroitin sulfate, sodium dermatan sulfate, potassium dermatan sulfate, etc.); amino acids such as alanine, serine, aspartic acid, glycine, glutamine, glutamic acid, proline, hydroxyproline, glucosamine, theanine, arginine and their derivatives; polyhydric alcohols such as glycerin, 1,2-propanediol, 1,3-propanediol, dipropylene glycol, 1,3-butanediol, diglycerin, pentylene glycol, polyethylene glycol, polypropylene glycol, etc.; sugar alcohols such as sorbitol, xylitol, erythritol, maltose·sucrose condensate (glucooligosaccharide), hydrolyzed xylan (xylooligosaccharide), etc.; alkylene oxides such as PPG-17 buteth-17, PPG-25 sorbitol, polyoxyalkylene alkyl glucoside, PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerin, polyoxyalkylene diglyceryl, etc.; glycosyl trehalose, trehalose; ceramide, pseudo-ceramide, glucosyl ceramide, cholesterol, phytosterol, cholesterol derivatives, phytosterol derivatives,; phospholipids such as lecithin, hydrogenated lecithin, etc.; 2-methacryloyloxyethyl phosphorylcholine·butyl methacrylate copolymer solution, 2-methacryloyloxy phosphorylcholine-containing polymers such as polymethacryloyloxyethyl phosphorylcholine, etc.; NMF-derived components such as lactic acid, sodium lactate, sodium pyrrolidone carboxylate, urea, etc.;Collagen, elastin, keratin, chitin, chitosan, etc. and their hydrolyzates; hydroxyethyl urea; components derived from plants (e.g., aloe, seaweed, turmeric, chlorella, lemongrass, chamomile, witch hazel, tea, perilla, grapefruit, amacha-zuru, etc.), etc. are mentioned.

[0068] Examples of antioxidants include dibutylhydroxytoluene (BHT), butylhydroxyanisole (BHA), sodium sulfite, erythorbic acid, L-cysteine hydrochloride, vitamin Cs, etc. Examples of vitamin Cs include, for example, ascorbigen-A, ascorbyl stearate, ascorbyl palmitate, L-ascorbyl dipalmitate, ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbyl phosphate, sodium ascorbate phosphate, magnesium ascorbyl phosphate, etc.

[0069] Examples of cooling agents include, but are not limited to, menthol (l-menthol, dl-menthol, etc.), camphor (d-camphor, dl-camphor, etc.), terpenoids such as borneol, essential oils containing terpenoids (perilla oil), or pharmacologically acceptable salts thereof, etc. One or more of these agents can also be used in appropriate combination.

[0070] Examples of preservatives include benzoic acid, sodium benzoate, acetic acid, dehydroacetic acid, sodium dehydroacetate, isobutyl p-hydroxybenzoate, isopropyl p-hydroxybenzoate, butyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, benzyl p-hydroxybenzoate, methyl p-hydroxybenzoate, phenol, phenoxyethanol, phenethyl alcohol, benzyl alcohol, iodine tincture, chlorobutanol, etc.

[0071] Examples of the chelating agent include ethylenediaminetetraacetic acid (EDTA), ethylenediaminetetraacetate (sodium salt (sodium edetate: Japanese Pharmacopoeia, EDTA-2Na, etc.), potassium salt, etc.), phytic acid, gluconic acid, polyphosphoric acid, metaphosphoric acid, etc. Among them, sodium edetate is preferred.

[0072] Examples of the pH adjuster 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.), inorganic bases (potassium hydroxide, sodium hydroxide, etc.), organic bases (triethanolamine, diisopropanolamine, triisopropanolamine, basic amino acids, etc.). Examples of the basic amino acids include lysine, histidine, arginine, etc.

[0073] Examples of the buffer include buffer solutions such as phosphates, acetates, carbonates, and citrates.

[0074] Examples of the coloring agent include inorganic pigments, natural pigments, etc.

[0075] The external liquid composition of the present invention can further contain other active ingredients as long as the effects of the present invention are not impaired. Specific examples of such components include, for example, moisturizing components, blood circulation promoting components, astringent components, peptides or their derivatives, amino acids or their derivatives, cell activation components, vitamin agents, etc.

[0076] [pH] The pH of the external liquid composition of the present invention is appropriately set according to the type of the component (A), the types and contents of other compounding components, the dosage form, the method of use, etc., and is not limited as long as it is within a physiologically or pharmaceutically acceptable range. From the viewpoint of safety, for example, it can be pH 2 to 9, preferably about 3 to 8, more preferably about 5 to 7.

[0077] [Viscosity] From the perspective of ease of handling of the preparation, the viscosity of the external liquid composition of the present invention is preferably 100 mPa·s to 10 Pa·s, more preferably 1 Pa·s to 8 Pa·s, and even more preferably 3 Pa·s to 6 Pa·s, based on the total amount of the external liquid composition. The viscosity described in this specification is the result obtained when measured using an RB80 viscometer manufactured by Toki Sangyo Co., Ltd., with an M3 rotor at a rotational speed of 12 rpm and a measurement time of 1 minute.

[0078] [Use] The external liquid composition of the present invention is an external liquid composition for being applied in a foamed state. The external liquid composition of the present invention is preferably used, although not limited thereto, on the skin, particularly on skin sites with a large area where it is necessary to spread the composition widely. This is because of the ease of handling peculiar to foam. Such skin sites preferably include the lower limbs, upper limbs, the back of the trunk, the front of the trunk, more preferably the arms, legs, back, abdomen, buttocks, and décolletage. Also, on these skin sites, it is particularly preferably used for delicate skin, for example, skin having the following symptoms or sensitive skin. This is because since the liquid composition of the present invention is in a foamed state, it can be spread without strongly touching the affected area. The external liquid composition of the present invention is used for the treatment, prevention, or alleviation of dryness symptoms of the skin, or for the treatment, prevention, or alleviation of symptoms based on blood circulation disorders. For example, it is used for the treatment, prevention, or alleviation of skin diseases accompanied by itching, senile xerosis, atopic dermatitis, dry skin diseases such as housewife's eczema, inflammatory skin diseases, pruritus cutis, razor burn, miliaria, chilblain, cracks, erythema, seborrhea deficiency, progressive palmoplantar keratoderma, frostbite, hypertrophic scar·keloid, pain or inflammatory diseases based on blood circulation disorders, thrombophlebitis, swelling after trauma (contusion, sprain, bruise), stiffness, swelling·hematoma·tendovaginitis·myalgia·arthritis, etc.

[0079] Also, the method of using the external liquid composition of the present invention varies depending on the condition of the affected area such as the skin, age, gender, etc., but for example, the following method may be used. That is, apply an appropriate amount (for example, about 0.5 to 2 g) in a foamed state to the affected area 1 to several times a day (for example, about 1 to 5 times, preferably 1 to 3 times, more preferably 1 time).

[0080] [Method for forming good-extending foam] In the present invention, there is also provided a method for forming good-extending foam by co-existing (A) a heparin-like substance; and (B) one or more compounds selected from the group consisting of glycyrrhetinic acid, a derivative of 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 chlorotone. Preferably, such foam can also be flexible and highly adhesive. Furthermore, the foam is easy to extend and conform on the skin. Here, the same conditions as the concentration of each component, pH, formulation conditions, etc. in the above-mentioned external liquid composition of the present invention are adopted.

Example

[0081] Next, the present invention will be specifically described by way of examples and test examples, but the present invention is not limited to the following examples and test examples.

[0082] The components listed in Table 1 were mixed separately in the aqueous phase and the oil phase, and these were prepared by a conventional method to obtain an external liquid composition. Next, the composition and liquefied petroleum gas (LPG) were filled into a foam discharge aerosol container at a mass ratio of 92:8.

[0083] [Test Example 1. Foam Drop Evaluation Test 1] At 25°C and a relative humidity of 50±5%, 0.5 g of the compositions of the examples and comparative examples were spray-coated on artificial leather. Next, the artificial leather was fixed vertically against the experimental table. The moment when the artificial leather (Idemitsu Techno Film Co., Ltd., product number: PBZ13001) was set vertically was taken as 0 seconds, and after a certain time, the distance that the foam advanced (the foam fell due to gravity) was examined. At this time, depending on the formulation of the composition, a part of the foam may collapse and drip as a liquid, but taking the position of the lowermost part of the largest foam body as 0 cm, the difference between the position of the lowermost part of the foam after a certain time was taken as the distance. The evaluation results are shown in Table 2.

[0084] [Test Example 2. Evaluation Test on the Firmness of Foam] At 25°C and a relative humidity of 50 ± 5%, 1.5 g of the compositions of the examples and comparative examples were sprayed into a 10 mL glass beaker (bottom diameter: 3.0 cm). After about 15 seconds had elapsed since spraying, a 10-yen coin was placed on top of this, and the time until one side of the 10-yen coin was completely in contact with the bottom of the beaker, that is, the time until it completely sank, was measured. The results of this evaluation are shown in Table 3.

[0085] [Test Example 3. Foam Drop Evaluation Test 2] At 25°C and a relative humidity of 50 ± 5%, 1.0 g each of the compositions of the examples and comparative examples were spray-coated onto artificial leather. Next, the artificial leather was turned over so that the non-spray-coated side of the composition faced upward, and the upper surface was fixed. Starting from the moment of fixing as 0 seconds, the time it took for the largest foam body to fall was examined. As a result, for the compositions of Examples 1 to 5, they did not fall 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 was found that the bubbles formed by the compositions of the examples were more likely to move vertically downward due to gravity compared to the compositions of the comparative examples, and were also more likely to collapse due to the gravity of the 10-yen coin. That is, it was found that the bubbles formed by the compositions of the examples were easily crushed with a weak force and had good extensibility.

[0090] From Test Example 3, it was found that although the bubbles formed by the compositions of the examples had been demonstrated to have good extensibility in Test Example 1, they were difficult to fall. That is, it was found that the bubbles formed by the compositions of Examples 1 to 5 had high adhesiveness.

[0091] The following are formulation examples of the present invention. An external liquid composition is prepared by a conventional method according to the formulation described in Table 4. All formulation examples are prepared in a form that is housed in a container and forms foam. The formulations of Formulation Examples 1 to 9 are each housed in an aerosol container for discharging foam including a pump former container and a propellant.

[0092] [Table 4]

Claims

1. (A)0.01 to 0.5% by mass of a heparin analogue; and (B)0.2 to 10% by mass of one or more compounds selected from the group consisting of glycyrrhetinic acid and / or its salt, glycyrrhizic acid and / or its salt, allantoin, tocopherol acetate, chlorpheniramine maleate, diphenhydramine and / or its salt, lidocaine and / or its salt, dibucaine and / or its salt, and chlorothen; Water and ethanol Contained in a foam discharge container of an aerosol containing a propellant, and is an external liquid composition (however, excluding an aerosol composition characterized by containing polyoxyethylene sterol, a solvent, and a propellant).

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

1.

3. The external liquid composition according to Claim 1 or 2, wherein the ratio of component (B) to component (A) is 0.3 to 35 parts by mass with respect to 1 part by mass of the content of component (A).

4. (A)0.01 to 0.5% by mass of a heparin analogue; and (B)0.2 to 10% by mass of one or more compounds selected from the group consisting of glycyrrhetinic acid and / or its salt, glycyrrhizic acid and / or its salt, allantoin, tocopherol acetate, chlorpheniramine maleate, diphenhydramine and / or its salt, lidocaine and / or its salt, dibucaine and / or its salt, and chlorothen; By coexisting water and ethanol in the composition and filling it into a foam discharge container of an aerosol containing a propellant and applying it, a method of forming good - stretching foam (however, excluding the case where the composition is an aerosol composition characterized by containing polyoxyethylene sterol, a solvent, and a propellant).

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