Topical pharmaceutical composition

Abstract

To provide a topical composition containing minoxidil, capable of suppressing discoloration over time and / or improving comb-through property.SOLUTION: The present invention relates to a topical composition containing minoxidil and a quaternary ammonium salt, the quaternary ammonium salt being an alkyltrimethylammonium salt having a long-chain alkyl group in which the alkyl has 10 or more carbon atoms. The invention enables provision of a minoxidil-containing topical composition that suppresses discoloration over time and / or improves comb-through property.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a topical composition containing minoxidil. More specifically, it relates to a technology for suppressing discoloration of a minoxidil-containing topical composition over time and improving the unpleasant sensation of use caused by application. [Background technology]

[0002] Minoxidil, whose chemical name is 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, is known to be used as a hair growth agent (see U.S. Pat. No. 4,139,619), and there have been many reports of it being a drug that exhibits excellent hair growth and hair regrowth effects.

[0003] It is known that liquid preparations containing minoxidil are prone to discoloration over time, and methods have been reported to prevent discoloration by adding amino acids (Patent Document 1), storing the preparation in a specific container (Patent Document 2), or adding an antioxidant such as dibutylhydroxytoluene to achieve a specific pH (Patent Document 3).

[0004] Furthermore, because minoxidil-containing preparations are used daily on the scalp over an extended period of time, lotions that also offer an excellent feel when used are required, and Patent Document 4 describes a minoxidil-containing lotion that provides good combing performance. As such, various studies have been conducted on the issues of coloring and combing performance of minoxidil-containing compositions, and various means have been investigated to suppress coloring, improve the feel when used, and so on, in order to further increase product value.

[0005] Cetrimide is classified as an alkyltrimethylammonium bromide and is widely used in over-the-counter medicines as a bactericidal and disinfectant agent. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] WO99 / 27966 [Patent Document 2] JP 8-198762 [Patent Document 3] Patent Publication No. 2001-288090 [Patent Document 4] Patent Publication No. 2020-105217 Summary of the Invention [Problem to be solved by the invention]

[0007] To provide a minoxidil-containing external composition that inhibits coloring over time and / or improves combability. [Means for solving the problem]

[0008] As a result of extensive research to solve the above problems, the inventors discovered that adding a certain type of quaternary ammonium salt to a minoxidil-containing composition can suppress the discoloration of minoxidil and improve combability, leading to the completion of the present invention. That is, the present invention provides: (1) A topical composition containing minoxidil and a quaternary ammonium salt, wherein the quaternary ammonium salt is an alkyltrimethylammonium salt having a long-chain alkyl group with 10 or more carbon atoms; (2) a composition for external use containing minoxidil and at least one quaternary ammonium salt selected from the group consisting of dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide, and tetradecyltrimethylammonium chloride; (3) a topical composition containing minoxidil and cetrimide; (4) The composition for external use according to any one of (1) to (3), which is a liquid, a lotion, a tonic, an aerosol, or a gel. (5) The topical composition according to any one of (1) to (4), which contains an alcohol having 2 to 6 carbon atoms. (6) The composition for external use according to any one of (1) to (5), which contains a Lewis acid having a pKa of 7.0 or less. (7) The composition for external use according to (6), wherein the Lewis acid having a pKa of 7.0 or less is at least one selected from the group consisting of phosphoric acid and citric acid. (8) The composition for external use according to any one of (1) to (3), wherein the content of minoxidil is 5 to 10 w / v%. (9) A composition for external use according to any one of (1) to (3), which contains a polyhydric alcohol. (10) The external pharmaceutical preparation according to (9), wherein the polyhydric alcohol is at least one selected from the group consisting of 1,3-butylene glycol, dipropylene glycol, propylene glycol, glycerin, and polyethylene glycol. is. [Effects of the Invention]

[0009] The present invention makes it possible to provide a minoxidil-containing topical composition that suppresses discoloration and / or improves combability. DETAILED DESCRIPTION OF THE INVENTION

[0010] The minoxidil used in the topical composition of the present invention can be of the same quality as that used in ordinary pharmaceuticals. The content of minoxidil used in the present invention is preferably 1 w / v% or more, more preferably 1 to 15 w / v%, and even more preferably 5 to 10 w / v%, based on the total content of the topical composition, from the viewpoint of increasing the problems of coloration and combability. At a content of 5 w / v% or more, the coloration of the formulation progresses and combability becomes difficult, so it is important to keep the content within this range in the present invention.

[0011] The quaternary ammonium salt in the present invention is an alkyltrimethylammonium salt having a long-chain alkyl group with 10 or more carbon atoms. An alkyltrimethylammonium salt is a substance in which an alkyltrimethylammonium cation and a counter anion form an ionic bond. In the present invention, although not particularly limited, alkyltrimethylammonium chloride or alkyltrimethylammonium bromide is preferred, such as decyltrimethylammonium bromide, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide, octadecyltrimethylammonium bromide, icosyltrimethylammonium bromide, decyltrimethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, hexadecyltrimethylammonium chloride, octadecyltrimethylammonium chloride, icosyltrimethylammonium chloride, docosyltrimethylammonium chloride, and octacosyltrimethylammonium chloride.

[0012] From the viewpoints of manufacturability and skin irritation, the quaternary ammonium salt in the present invention is more preferably an alkyltrimethylammonium chloride or alkyltrimethylammonium bromide having a long-chain alkyl group of 12 to 20 alkyls, such as dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide, octadecyltrimethylammonium bromide, icosyltrimethylammonium bromide, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride ... Preferred are alkyltrimethylammonium chloride, octadecyltrimethylammonium chloride, and icosyltrimethylammonium chloride, and more preferred are alkyltrimethylammonium chlorides or alkyltrimethylammonium bromides having a long-chain alkyl group of 12 to 16, such as dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, and hexadecyltrimethylammonium chloride. Among alkyltrimethylammonium chlorides and alkyltrimethylammonium bromides, alkyltrimethylammonium bromides are preferred, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, and hexadecyltrimethylammonium bromide are even more preferred, and tetradecyltrimethylammonium bromide is particularly preferred.

[0013] The topical composition of the present invention may contain two or more of the quaternary ammonium salts of the present invention, such as a combination of dodecyltrimethylammonium bromide and tetradecyltrimethylammonium bromide, or a combination of tetradecyltrimethylammonium bromide and hexadecyltrimethylammonium bromide, or may contain all of dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, and hexadecyltrimethylammonium bromide.

[0014] The content of the quaternary ammonium salt in the present invention (the total amount if multiple quaternary ammonium salts are contained, the same applies below) is not particularly limited, but is preferably 0.1 to 5 w / v%, and more preferably 0.4 to 2 w / v%, in the topical composition of the present invention.

[0015] The cetrimide of the present invention can be of the same quality as that used in ordinary pharmaceuticals. Cetrimide is primarily composed of tetradecyltrimethylammonium bromide and may contain small amounts of dodecyltrimethylammonium bromide and hexadecyltrimethylammonium bromide. The content of cetrimide in the topical composition of the present invention is not particularly limited, but is preferably 0.1 to 5 w / v%, more preferably 0.4 to 2 w / v%.

[0016] The topical composition of the present invention may contain an alcohol having 2 to 6 carbon atoms as a solubilizing agent for minoxidil. The alcohol having 2 to 6 carbon atoms is not particularly limited, and a monohydric or polyhydric alcohol can be used, such as ethanol, propylene glycol, 1,3-butylene glycol, glycerin, dipropylene glycol, polyethylene glycol, pentylene glycol, and hexylene glycol. From the viewpoint of the stability and solubility of minoxidil, ethanol, propylene glycol, 1,3-butylene glycol, and glycerin are preferred, and ethanol, propylene glycol, and 1,3-butylene glycol are more preferred. These alcohols may be used alone or in combination. The content of the alcohol having 2 to 6 carbon atoms (the total amount when multiple alcohols are present, the same applies hereinafter) is preferably 10 to 90 w / v%, more preferably 35 to 75 w / v%, of the total composition.

[0017] The topical composition of the present invention may contain a Lewis acid having a pKa of 7.0 or less as a solubilizing agent for minoxidil. Examples of Lewis acids include hydrochloric acid, sulfuric acid, phosphoric acid, lactic acid, citric acid, acetic acid, tartaric acid, maleic acid, malic acid, gluconic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, and isostearic acid. From the viewpoint of the stability and solubility of minoxidil, phosphoric acid, citric acid, lactic acid, tartaric acid, and malic acid are preferred, and phosphoric acid and citric acid are more preferred. These acids may be used alone or in combination.

[0018] Furthermore, in terms of minoxidil stability and skin irritation during use, the pH of the topical composition of the present invention is preferably 4.0 to 9.0, more preferably 5.0 to 7.0, and even more preferably 5.5 to 6.5.

[0019] In addition to the above-mentioned components, the topical composition of the present invention may contain other active ingredients and auxiliary ingredients as needed, provided that the effects of the present invention are not impaired. Examples of medicinal ingredients that are preferably added or incorporated into the topical composition of the present invention include one or more components selected from the group consisting of menthol, vitamin E acetate, hinokitiol, pyridoxine hydrochloride, glycyrrhetinic acid, diphenhydramine hydrochloride, pantothenyl ethyl ether, and panthenol. The amounts of these ingredients added are not particularly limited and can be determined taking into consideration the feel when used, the stability of minoxidil, the composition of the solvent system, etc.

[0020] In addition to the above-mentioned components, the topical composition of the present invention can contain various active ingredients and auxiliary ingredients used in general topical preparations, provided that the effects of the present invention are not impaired. For example, excipients, hair growth ingredients (6-benzylaminopurine, adenosine, pentadecanoic acid glyceride, Polygonum polyglutamum, etc.), vasodilators (carpronium chloride, benzyl nicotinate, Swertia japonica extract, Panax ginseng extract, Panax ginseng tincture, Capsicum tincture, etc.), antihistamines (isothipendyl hydrochloride, etc.), anti-inflammatory agents (guaiazulene, etc.), keratolytic agents (salicylic acid, etc.), disinfectants (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, piroctone olamine, etc.), moisturizers (hyaluronic acid or its salts, chondroitin sulfate, etc.), various plants and animals (yew, moutan pith, licorice, St. John's wort, aconite, loquat, artemisia capillaris, comfrey, angelica tree, saffron, Sanshishi, rosemary, Sesamum indicum, It can contain commonly used ingredients such as extracts of vegetables (such as ginger, bamboo shoots, bamboo shoots, hops, placenta, saw palmetto, pumpkin seeds, etc.), vitamins (ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, etc.), antioxidants (dibutylhydroxytoluene, sodium metabisulfite, tocopherol, sodium edetate, ascorbic acid, isopropyl gallate, etc.), solubilizers (diisopropyl adipate, isopropyl myristate, various vegetable oils, various animal oils, alkyl glyceryl ethers, hydrocarbons, etc.), pH adjusters (organic acids such as citric acid, malic acid, lactic acid, tartaric acid, and inorganic acids such as hydrochloric acid and sulfuric acid), metabolic activators, gelling agents, adhesives, fragrances, fresheners (peppermint oil, camphor, etc.), and dyes.

[0021] Furthermore, the topical composition of the present invention is preferably a liquid, a lotion, a tonic, a gel obtained by adding a gelling agent to a liquid to make it viscous, or an aerosol composed of a concentrate and a propellant. Furthermore, the topical composition of the present invention can be used as a pharmaceutical composition for topical application, and may also be used as a liquid pharmaceutical composition for topical application.

[0022] The topical composition of the present invention is prepared by incorporating the above-mentioned components according to a conventional method. For example, when preparing a lotion, minoxidil and the quaternary ammonium salt of the present invention are mixed with 1,3-butylene glycol and ethanol, and then an aqueous solution of phosphoric acid is added and stirred to obtain a clear solution. Then, purified water is added to the solution to the desired volume to complete the preparation.

[0023] The thus obtained external composition of the present invention can be used as a skin application preparation such as a hair preparation, eyelash preparation, or eyebrow preparation.

[0024] The container for housing the topical composition of the present invention is not particularly limited, and examples thereof include bottle containers, aerosol containers, and aluminum pillow containers.

[0025] Examples of materials for the bottle container include PET (polyethylene terephthalate), PE (polyethylene), PP (polypropylene), and glass, with PET being preferred. The bottle container may be a container that contains an amount for multiple uses, or a container that contains an amount for single use. In the case of a container that contains an amount for multiple uses, a fixed-dose type container is preferred, and the material of the application site is preferably polyethylene or polypropylene.

[0026] An aerosol container must be pressure-resistant enough to withstand the internal pressure of the aerosol and airtight enough to prevent leakage of the contents. As long as the pressure-resistant performance stipulated by regulations (not deforming at 1.3 MPa and not breaking at 1.5 MPa) is maintained, the material may be aluminum, glass, tinplate, or synthetic resin. When using a tinplate or aluminum container, the surface can be coated with resin to prevent corrosion, but aluminum containers are preferred from the viewpoint of versatility. Furthermore, the container used for the aerosol formulation of the present invention is preferably one that is equipped with a valve, button, spout, cap, etc. in addition to the pressure-resistant container, similar to known aerosol containers.

[0027] EXAMPLES The present invention will be explained in more detail below with reference to Examples, Comparative Examples, and Test Examples, but the present invention is not limited to these Examples in any way.

[0028] In Examples 5 to 9 and Comparative Examples 3 to 6, raw material grade 95% ethanol aqueous solution was used as ethanol, and a stainless steel beaker was used for stirring. [Example]

[0029] Example 1 5 g of minoxidil, 0.5 g of dodecyltrimethylammonium bromide, 10 g of 1,3-butylene glycol, 55 g of ethanol, 0.5 mL of phosphoric acid, and an appropriate amount of purified water were added and dissolved in a glass measuring flask with stirring, and purified water was added to make up the total volume to 100 mL to obtain a composition with a pH of 6.1.

[0030] Example 2 5 g of minoxidil, 0.5 g of tetradecyltrimethylammonium bromide, 10 g of 1,3-butylene glycol, 55 g of ethanol, 0.5 mL of phosphoric acid, and an appropriate amount of purified water were added and stirred in a glass measuring flask, and purified water was added to make up the total volume to 100 mL to obtain a composition with a pH of 6.1.

[0031] Example 3 5 g of minoxidil, 0.5 g of hexadecyltrimethylammonium bromide, 10 g of 1,3-butylene glycol, 55 g of ethanol, 0.5 mL of phosphoric acid, and an appropriate amount of purified water were added and stirred in a glass measuring flask to dissolve the mixture, and then purified water was added to make up the total volume to 100 mL to obtain a composition with a pH of 6.1.

[0032] Example 4 Minoxidil 5g, cetrimide 0.25g, 1,3-butylene glycol 5g, glycerin 5.9g, ethanol 25g, phosphoric acid 0.25mL, citric acid 0.5g, and an appropriate amount of purified water were added, and the mixture was stirred and dissolved in a stainless steel beaker, and purified water was added to make up the total volume to 50mL to obtain a composition. The pH of the prepared composition was 6.2.

[0033] Example 5 2.5 g of minoxidil, 0.25 g of cetrimide, 5 g of 1,3-butylene glycol, 28.95 g of 95% ethanol, 0.25 mL of phosphoric acid, and an appropriate amount of purified water were added, stirred, and dissolved in a stainless steel beaker. The total volume was adjusted to 50 mL with purified water to obtain a composition. The pH of the prepared composition was 6.1.

[0034] Example 6 2.5 g of minoxidil, 0.25 g of tetradecyltrimethylammonium chloride, 5 g of 1,3-butylene glycol, 28.95 g of 95% ethanol, 0.25 mL of phosphoric acid, and an appropriate amount of purified water were added, stirred, and dissolved in a stainless steel beaker. The total volume was adjusted to 50 mL with purified water to obtain a composition. The pH of the prepared composition was 6.1.

[0035] Example 7 2.5 g of minoxidil, 0.25 g of cetrimide, 5 g of 1,3-butylene glycol, 28.95 g of 95% ethanol, 0.25 g of citric acid, and an appropriate amount of purified water were added, stirred, and dissolved in a stainless steel beaker. The total volume was adjusted to 50 mL with purified water to obtain a composition. The pH of the prepared composition was 6.2.

[0036] Example 8 2.5 g of minoxidil, 0.25 g of cetrimide, 5.9 g of glycerin, 28.95 g of 95% ethanol, 0.25 mL of phosphoric acid, and an appropriate amount of purified water were added, stirred and dissolved in a stainless steel beaker, and the total volume was adjusted to 50 mL with purified water to obtain a composition. The pH of the prepared composition was 5.9.

[0037] Example 9 2.5 g of minoxidil, 0.25 g of cetrimide, 5 g of propylene glycol, 28.95 g of 95% ethanol, 0.25 mL of phosphoric acid, and an appropriate amount of purified water were added, stirred, and dissolved in a stainless steel beaker. The total volume was adjusted to 50 mL with purified water to obtain a composition. The pH of the prepared composition was 6.0.

[0038] (Comparative Example 1) 5 g of minoxidil, 10 g of 1,3-butylene glycol, 55 g of ethanol, 0.5 mL of phosphoric acid, and an appropriate amount of purified water were added and dissolved in a glass measuring flask with stirring, and purified water was added to make up the total volume to 100 mL to obtain a composition with a pH of 6.1.

[0039] (Comparative Example 2) 5g of minoxidil, 5g of 1,3-butylene glycol, 5.9g of glycerin, 25g of ethanol, 0.25mL of phosphoric acid, 0.5g of citric acid, and an appropriate amount of purified water were added, stirred and dissolved in a stainless steel beaker, and the total volume was adjusted to 50mL with purified water to obtain a composition. The pH of the prepared composition was 6.2.

[0040] (Comparative Example 3) 2.5 g of minoxidil, 5 g of 1,3-butylene glycol, 28.95 g of 95% ethanol, 0.25 mL of phosphoric acid, and an appropriate amount of purified water were added and stirred in a stainless steel beaker to dissolve, and then purified water was added to make up the total volume to 50 mL to obtain a composition. The pH of the prepared composition was 6.1.

[0041] Comparative Example 4 2.5 g of minoxidil, 5 g of 1,3-butylene glycol, 28.95 g of 95% ethanol, 0.25 g of citric acid, and an appropriate amount of purified water were added, stirred, and dissolved in a stainless steel beaker. The total volume was adjusted to 50 mL with purified water to obtain a composition. The pH of the prepared composition was 6.4.

[0042] (Comparative Example 5) 2.5 g of minoxidil, 5.9 g of glycerin, 28.95 g of 95% ethanol, 0.25 mL of phosphoric acid, and an appropriate amount of purified water were added and stirred in a stainless steel beaker to dissolve, and then purified water was added to make up the total volume to 50 mL to obtain a composition. The pH of the prepared composition was 5.9.

[0043] (Comparative Example 6) 2.5 g of minoxidil, 5 g of propylene glycol, 28.95 g of 95% ethanol, 0.25 mL of phosphoric acid, and an appropriate amount of purified water were added and stirred in a stainless steel beaker to dissolve the mixture. The total volume was adjusted to 50 mL with purified water to obtain a composition with a pH of 6.0.

[0044] (Thermal stability test) The test solutions of Examples 1 to 9 and Comparative Examples 1 to 6 were placed in ampoules (borosilicate glass) and stored at 65°C for 7 days, after which the absorbance was measured using a spectrophotometer. By measuring the absorbance at 420 nm, the coloration due to the decomposition of minoxidil was quantitatively evaluated.

[0045] (Comb-through evaluation) A combing evaluation was carried out for the test solutions of Examples 1 to 9 and Comparative Examples 1 to 6 using a hair tress sample (10 g, Chinese human hair, Beaulax). 2 The test solution was applied to a 4cm x 5cm area, and after air drying for about 24 hours, the combing ability (maximum load) was evaluated using an RZ-2 force gauge (Aiko Engineering Co., Ltd.). The measurement was repeated three times and the average value was calculated. Examples 1 to 3 and Comparative Example 1 were evaluated according to the following evaluation criteria. (Evaluation criteria) ◎: Maximum load less than 3N 〇: Maximum load is 3N or more and less than 5N △: Maximum load is 5N or more

[0046] [Table 1]

[0047] As is clear from Table 1, the minoxidil-containing compositions containing dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, and hexadecyltrimethylammonium bromide (Examples 1, 2, and 3) showed less coloration than the minoxidil-containing composition not containing these three components (Comparative Example 1).

[0048] As is clear from Table 1, the minoxidil-containing compositions containing dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, and hexadecyltrimethylammonium bromide (Examples 1, 2, and 3) had better combability than the minoxidil-containing composition not containing these three ingredients (Comparative Example 1).

[0049] [Table 2]

[0050] As is clear from Table 2, the minoxidil-containing composition containing cetrimide (Example 4) was less discolored than the minoxidil-containing composition not containing cetrimide (Comparative Example 2).

[0051] As is clear from Table 2, the minoxidil-containing composition containing cetrimide (Example 4) had better combability than the minoxidil-containing composition not containing cetrimide (Comparative Example 2).

[0052] [Table 3]

[0053] As is clear from Table 3, the minoxidil-containing compositions containing cetrimide or tetradecyltrimethylammonium chloride (Examples 5 and 6) showed less discoloration than the minoxidil-containing composition not containing cetrimide or tetradecyltrimethylammonium chloride (Comparative Example 3).

[0054] As is clear from Table 3, the minoxidil-containing compositions containing cetrimide or tetradecyltrimethylammonium chloride (Examples 5, 6, and 7) had better combability than the minoxidil-containing composition not containing cetrimide or tetradecyltrimethylammonium chloride (Comparative Example 3).

[0055] [Table 4]

[0056] As is clear from Table 4, the minoxidil-containing composition containing cetrimide (Example 7) was less discolored than the minoxidil-containing composition not containing cetrimide (Comparative Example 4).

[0057] As is clear from Table 4, the minoxidil-containing composition containing cetrimide (Example 7) had better combability than the minoxidil-containing composition not containing cetrimide (Comparative Example 4).

[0058] [Table 5]

[0059] As is clear from Table 5, the minoxidil-containing composition containing cetrimide (Example 8) was less discolored than the minoxidil-containing composition not containing cetrimide (Comparative Example 5).

[0060] As is clear from Table 5, the minoxidil-containing composition containing cetrimide (Example 8) had better combability than the minoxidil-containing composition not containing cetrimide (Comparative Example 5).

[0061] [Table 6]

[0062] As is clear from Table 6, the minoxidil-containing composition containing cetrimide (Example 9) was less discolored than the minoxidil-containing composition not containing cetrimide (Comparative Example 6).

[0063] As is clear from Table 6, the minoxidil-containing composition containing cetrimide (Example 9) had better combability than the minoxidil-containing composition not containing cetrimide (Comparative Example 6). [Industrial Applicability]

[0064] According to the present invention, it is possible to provide a minoxidil-containing composition that can suppress coloration over time in a composition containing cetrimide and that allows easy combing.

Claims

1. A topical composition containing minoxidil and a quaternary ammonium salt, wherein the quaternary ammonium salt is an alkyltrimethylammonium salt having a long-chain alkyl group with 10 or more carbon atoms.

2. A topical composition containing minoxidil and at least one quaternary ammonium salt selected from the group consisting of dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide and tetradecyltrimethylammonium chloride.

3. A topical composition containing minoxidil and cetrimide.

4. The composition for external use according to any one of claims 1 to 3, which is in the form of a liquid, lotion, tonic, aerosol, or gel.

5. The topical composition according to any one of claims 1 to 3, which contains an alcohol having 2 to 6 carbon atoms.

6. The topical composition according to any one of claims 1 to 3, comprising a Lewis acid having a pKa of 7.0 or less.

7. The topical composition according to claim 6, wherein the Lewis acid having a pKa of 7.0 or less is at least one selected from the group consisting of phosphoric acid and citric acid.

8. The composition for external use according to any one of claims 1 to 3, wherein the content of minoxidil is 5 to 10 w / v%.

9. The composition for external use according to any one of claims 1 to 3, which contains a polyhydric alcohol.

10. 10. The external pharmaceutical preparation according to claim 9, wherein the polyhydric alcohol is at least one selected from the group consisting of 1,3-butylene glycol, dipropylene glycol, propylene glycol, glycerin, and polyethylene glycol.

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