External composition

Abstract

To provide a minoxidil-containing composition for external use, blended with pyridoxine, which suppresses the precipitation caused by minoxidil which may occur after application, and also suppresses deterioration of stability of the pyridoxine.SOLUTION: There is provided a composition for external use which comprises minoxidil, pyridoxine and / or a salt thereof, propylene glycol and at least one acid selected from the group consisting of phosphoric acid, citric acid, lactic acid, hydrochloric acid, acetic acid, sulfuric acid, nitric acid, tartaric acid and maleic acid and / or a salt thereof. It can be used as a composition for external use such as a lotion, an aerosol, a tonic agent, a cream agent, an ointment and a gelling agent and the most preferable formulation of it is a lotion.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a topical composition containing minoxidil as an active ingredient. More specifically, the present invention relates to a technique for suppressing precipitation of minoxidil that may occur when applying a topical composition containing minoxidil that contains pyridoxine. [Background technology]

[0002] Minoxidil has the chemical name 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, and is known to be applicable as a hair growth agent (Patent Document 1). There have been many reports of it being a drug that exhibits excellent hair growth and hair regrowth effects. Since a minoxidil-containing topical composition is used on the scalp every day for a long period of time, a composition that is excellent in usability is required. When a composition with a high concentration of minoxidil is used, precipitation of minoxidil may occur after application, which may look like dandruff. Therefore, a composition that suppresses the precipitation of minoxidil that may occur after application in a topical composition containing minoxidil is desired. In addition, pyridoxine has been reported to have an effect of suppressing lipid synthesis (Non-Patent Document 1), and is used in many hair growth agents. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] U.S. Pat. No. 4,139,619 [Non-patent literature]

[0004] [Non-Patent Document 1] Effect of drugs on lipid synthesis in the sebaceous gland Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a minoxidil-containing topical composition for topical use that contains pyridoxine and that inhibits precipitation derived from minoxidil that may occur after application. [Means for solving the problem]

[0006] As a result of extensive research aimed at solving the above problems, the inventors discovered that a composition containing minoxidil, pyridoxine, a specific polyhydric alcohol, and a specific acid can inhibit precipitation derived from minoxidil, and thus completed the present invention.

[0007] That is, the present invention provides: (1) A composition for external use, comprising 1) minoxidil, 2) pyridoxine and / or a salt thereof, 3) propylene glycol, and 4) at least one acid and / or a salt thereof selected from the group consisting of phosphoric acid, citric acid, lactic acid, hydrochloric acid, acetic acid, sulfuric acid, nitric acid, tartaric acid, and maleic acid, (2) The composition for external use according to (1), wherein the concentration of minoxidil is 5 w / w% or more. It is. Effect of the Invention

[0008] According to the present invention, it is possible to suppress the precipitation of minoxidil that may occur after application in a minoxidil-containing topical composition containing pyridoxine. Furthermore, unexpectedly, it is possible to provide a clear minoxidil-containing composition that does not produce any precipitate in the formulation, and to suppress the deterioration of the stability of pyridoxine and / or its salt over time. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] According to the present invention, a topical composition containing minoxidil, pyridoxine and / or a salt thereof, propylene glycol, and a specific acid and / or a salt thereof suppresses precipitation derived from minoxidil that may occur after application, does not produce precipitates in the formulation, and suppresses a decrease in the stability of pyridoxine.

[0010] The minoxidil used in the external composition of the present invention can be of the quality generally used in pharmaceutical products.In addition, according to the present invention, the higher the content of minoxidil, the greater the problem of precipitation that may occur after application of the preparation, so the higher the concentration of minoxidil in the external composition, the greater the significance of carrying out the present invention.Specifically, the content of minoxidil in the external composition of the present invention is 1 w / w% or more, more preferably 3 w / w% or more, and even more preferably 5 w / w% or more.

[0011] From the viewpoint of the effect of the present invention that a clear preparation without precipitation can be obtained, the specific acid and / or salt thereof in the composition for external use of the present invention is phosphoric acid, citric acid, lactic acid, hydrochloric acid, acetic acid, sulfuric acid, nitric acid, tartaric acid, maleic acid, or a salt thereof, preferably phosphoric acid, citric acid, lactic acid, or tartaric acid. These acids and / or salts thereof are components that adjust the liquidity of the composition for external use of the present invention to 7 or less, and are all inorganic acids or salts thereof, or organic acids or salts thereof having 6 or less carbon atoms. The specific acids and / or salts thereof of the present invention may be used alone or in combination of two or more kinds.

[0012] The polyhydric alcohol used in the topical composition of the present invention is propylene glycol, which is an effect of the present invention, in that it does not cause precipitation derived from minoxidil after application. The amount of propylene glycol is preferably 2 to 55 w / w% of the total composition, more preferably 5 to 35 w / w%. The topical composition of the present invention may contain a polyhydric alcohol other than propylene glycol within a range that does not impair the effect of the present invention, but it is preferable not to add glycerin or polyethylene glycol in terms of the effect of the present invention, and it is most preferable to add only propylene glycol in terms of the effect of the present invention.

[0013] In addition, the pH of the topical composition of the present invention is preferably adjusted to a range of 4.0 to 9.5, more preferably 5.0 to 7.0, from the viewpoints of the stability of the main ingredient minoxidil, the irritation to the skin during use, the permeability of the drug, the feeling of use, etc. Furthermore, the upper limit of the pH is preferably less than 6.5, more preferably 6.3 or less, and even more preferably 6.1 or less.

[0014] The amount of pyridoxine used in the topical composition of the present invention is preferably 0.01 to 2 w / w%, more preferably 0.03 to 0.1 w / w%, and even more preferably 0.03 to 0.05 w / w%, in terms of the effects of the present invention.

[0015] The composition for external use of the present invention may further contain a higher alcohol if necessary. Examples of higher alcohols include diacetone alcohol, caproyl alcohol, caprylyl alcohol, capryl alcohol, lauryl alcohol, tridecanol, myristyl alcohol, pentadecanol, cetyl alcohol, hexyl decanol, isocetyl alcohol, cetostearyl alcohol, heptadecanol, stearyl alcohol, oleyl alcohol, isostearyl alcohol, octyl decanol, nonadecanol, arachidyl alcohol, octyldodecanol, henicosanol, behenyl alcohol, and decyl tetradecanol, which have 6 to 24 carbon atoms, and among these, diacetone alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, hexyl decanol, cetostearyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, arachidyl alcohol, octyldodecanol, behenyl alcohol, and decyl tetradecanol are more preferred. The higher alcohols of the present invention may be used alone or in combination of two or more. The amount of the higher alcohol in the total composition is preferably 0.05 to 2 w / w %, more preferably 0.1 to 1.5 w / w %, and even more preferably 0.25 to 1.5 w / w %.

[0016] The composition for external use of the present invention may further contain lower alcohols and water as necessary. The lower alcohols are preferably those having 1 to 5 carbon atoms, such as ethanol and isopropanol, and may be used in combination. The amount of the lower alcohol is preferably 20 w / w% or more of the total composition, more preferably 30 w / w% or more, more preferably 35 w / w% or more, and even more preferably 50 w / w% or more. The amount of water is preferably 2 to 75 w / w%, more preferably 5 to 50 w / w%.

[0017] The composition for external use of the present invention may further contain a higher fatty acid if necessary. Examples of higher fatty acids include those having 10 to 22 carbon atoms, such as isostearic acid, oleic acid, stearic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, linoleic acid, linolenic acid, elaidic acid, arachidic acid, arachidonic acid, behenic acid, eicosapentaenoic acid, and docosahexaenoic acid, and may be used alone or in combination of two or more. Among these, those having 18 carbon atoms are preferred, and isostearic acid or oleic acid are particularly preferred. The amount of higher fatty acid is preferably 0.1 to 10 w / w% of the total composition, and more preferably 1 to 6 w / w%.

[0018] The topical composition of the present invention may further contain a surfactant if necessary. However, the addition of a surfactant may affect the feel during use and the dermal absorption of minoxidil, and since the topical composition of the present invention can ensure the solubility of minoxidil without the incorporation of a surfactant, it is preferable that the topical composition of the present invention does not substantially contain a surfactant.

[0019] In addition to the above-mentioned components, the composition for external use of the present invention may contain necessary active ingredients and auxiliary ingredients within the range that does not impair the effects of the present invention. Examples of medicinal ingredients that are preferably added or blended into the lotion of the present invention include ingredients selected from the group consisting of menthol, vitamin E acetate, pantothenyl ethyl ether, hinokitiol, glycyrrhetinic acid, diphenhydramine hydrochloride, and panthenol. There are no particular restrictions on the amounts of these optional ingredients added, and they can be determined experimentally, taking into consideration the feel when used, the stability of minoxidil, the composition of the solvent system, and the like.

[0020] In addition to the above-mentioned components, the topical composition of the present invention may 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 polycutrum, 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 (urea, salicylic acid, etc.), bactericides (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, piroctone olamine, etc.), moisturizers (hyaluronic acid or its salts, chondroitin sulfate, etc.), various plants and animals (yew, moutan pi, licorice, Hypericum perforatum, aconite, loquat, artemisia capillaris, comfrey, angelica tree, saffron). It can contain commonly used ingredients such as extracts of Japanese laurel, rosemary, sage, bamboo shoots, Japanese laurel, hops, placenta, saw palmetto, pumpkin seed, etc.), vitamins (retinol acetate, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, etc.), antioxidants (dibutylhydroxytoluene, sodium pyrosulfite, tocopherol, sodium edetate, ascorbic acid, isopropyl gallate, etc.), solubilizers (diisopropyl adipate, isopropyl myristate, various vegetable oils, various animal oils, alkyl glyceryl ethers, hydrocarbons, etc.), metabolic activators, gelling agents (water-soluble polymers, etc.), adhesives, fragrances, refreshing agents (peppermint oil, camphor, etc.), dyes, etc.

[0021] The topical composition of the present invention can be in the form of a suitable topical composition such as a lotion, aerosol, tonic, cream, ointment, gel, etc. Among these, the most preferred dosage form is a lotion.

[0022] The topical composition of the present invention can be prepared by incorporating the above-mentioned components in a conventional manner.

[0023] The thus obtained composition for external use of the present invention can be used as a preparation for application to the skin, such as a preparation for hair, eyelashes, or eyebrows.

[0024] 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. EXAMPLES

[0025] Example 1 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of phosphoric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0026] Example 2 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of citric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.1.

[0027] Example 3 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of lactic acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.1.

[0028] Example 4 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of hydrochloric acid, an appropriate amount of purified water 20 g, and ethanol were added to bring the total volume to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0029] Example 5 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of acetic acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use having a pH of 6.1.

[0030] Example 6 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of sulfuric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use having a pH of 6.0.

[0031] Example 7 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of nitric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0032] Example 8 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of tartaric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use having a pH of 6.1.

[0033] Example 9 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of maleic acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use having a pH of 6.0.

[0034] Example 10 1 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of phosphoric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0035] Example 11 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of citric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0036] Example 12 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of lactic acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0037] Example 13 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of tartaric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0038] Comparative Example 1 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of polyethylene glycol 400, an appropriate amount of phosphoric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.3.

[0039] Comparative Example 2 A composition for external use was prepared by mixing 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of dl-malic acid, 20 g of purified water, and ethanol to a total volume of 100 g, and stirring for approximately 1 hour.

[0040] Comparative Example 3 A composition for external use was prepared by mixing 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of boric acid, 20 g of purified water, and ethanol to a total volume of 100 g, and stirring for approximately 1 hour.

[0041] Comparative Example 4 5 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of gluconic acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0042] Comparative Example 5 1 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of propylene glycol, an appropriate amount of gluconic acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use having a pH of 6.0.

[0043] Comparative Example 6 A composition for external use containing 1 g of minoxidil, 0.05 g of pyridoxine hydrochloride, 15 g of polyethylene glycol 400, an appropriate amount of phosphoric acid, 20 g of purified water, and ethanol was added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0044] Comparative Example 7 1 g of minoxidil, 15 g of propylene glycol, an appropriate amount of phosphoric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0045] Comparative Example 8 5 g of minoxidil, 15 g of propylene glycol, an appropriate amount of citric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.1.

[0046] Comparative Example 9 5 g of minoxidil, 15 g of propylene glycol, an appropriate amount of lactic acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0047] Comparative Example 10 5 g of minoxidil, 15 g of propylene glycol, an appropriate amount of tartaric acid, 20 g of purified water, and ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.0.

[0048] <Test Example 1: Precipitation Test-1> For Example 1 and Comparative Example 1, 100 μL of each of the compositions for external use was dropped onto a glass petri dish, and after 24 hours, the precipitation of crystals derived from minoxidil was visually evaluated. The test was carried out three times.

[0049] As a result of the test, compared with Comparative Example 1 in which polyethylene glycol was blended as the polyhydric alcohol, Example 1 in which the polyhydric alcohol of the present invention was used suppressed the precipitation of crystals derived from minoxidil all three times.

[0050] <Test Example 2: Precipitation Test-2> For Examples 10 to 13 and Comparative Examples 6 to 10, 100 μL of each of the compositions for external use was dropped onto a glass petri dish, and after 24 hours, the precipitation of crystals derived from minoxidil was visually evaluated.

[0051] As a result of the test, crystal precipitation derived from minoxidil was suppressed in Example 10, which used the polyhydric alcohol of the present invention, compared to Comparative Example 6, which used polyethylene glycol as the polyhydric alcohol. Also, crystal precipitation derived from minoxidil was suppressed in Example 10, which used the pyridoxine hydrochloride of the present invention, compared to Comparative Example 7, which did not contain pyridoxine hydrochloride.

[0052] Furthermore, in the preparations of the present invention using different types of acids, crystal precipitation derived from minoxidil was similarly suppressed (Examples 11 to 13 and Comparative Examples 8 to 10).

[0053] <Test Example 3: Preparation test of lotion> Preparation tests of lotions were carried out for Examples 1 to 10 and Comparative Examples 2 to 5. After preparation, the lotions in the beakers were visually inspected, and clear preparations without precipitates were marked with an O, and those with precipitates in the lotions were marked with an X. The results are shown in Table 1.

[0054] <Test Example 4: Stability test of pyridoxine hydrochloride> Stability tests of pyridoxine hydrochloride were carried out for Examples 1 to 10 and Comparative Examples 4 to 5. The stability tests were carried out by leaving each composition in an incubator at 65°C for 2 weeks, and then quantifying the pyridoxine hydrochloride content by liquid chromatography. The pyridoxine hydrochloride content was compared with that immediately after preparation, and a drop of 0 to 5% was marked with ◎, a drop of 6 to 7% was marked with ○, a drop of 8 to 9% was marked with △, and a drop of 10% or more was marked with ×. The results are shown in Table 1.

[0055] [Table 1]

[0056] As is clear from Table 1, in Examples 1 to 10 in which the acid of the present invention was used, all of the ingredients were dissolved, and clear lotions without precipitate were obtained. On the other hand, in the case in which malic acid or boric acid was used as the acid, precipitate was generated in the lotion after preparation (Comparative Examples 2 and 3). In Comparative Examples 4 and 5, in which gluconic acid was used as the acid, lotions could be prepared, but the pyridoxine hydrochloride content was significantly reduced. On the other hand, in the lotions of Examples 1 to 10 in which the acid of the present invention was used, the pyridoxine hydrochloride content reduction was less than 10%. In particular, when phosphoric acid, hydrochloric acid, acetic acid, sulfuric acid, or nitric acid was used, the reduction in pyridoxine hydrochloride content could be suppressed to 5% or less, which was a preferable result. [Industrial Applicability]

[0057] According to the present invention, it is now possible to provide an excellent minoxidil-containing topical composition containing pyridoxine, which inhibits precipitation derived from minoxidil that may occur after application, inhibits the formation of precipitates in the topical composition, and inhibits a decrease in the stability of pyridoxine and / or a salt thereof.

Claims

1. An additive comprising pyridoxine hydrochloride for inhibiting precipitation derived from minoxidil that occurs after application of an external pharmaceutical composition containing (a) minoxidil, (b) tartaric acid, and (c) 5 to 35 w / w % propylene glycol, The pharmaceutical composition for external application contains 20 w / w % or more of ethanol and 2 to 75 w / w % of water, and does not contain polyethylene glycol; The pH of the pharmaceutical composition for external application after adding the additive is 5.0 to 7.0; The amount of pyridoxine hydrochloride in the topical pharmaceutical composition after adding the additive is 0.05 g per 5 g of minoxidil.

2. The additive according to claim 1, which is added to the external pharmaceutical composition so that the amount of pyridoxine hydrochloride contained therein is in the range of 0.01 to 2 w / w %.

3. The additive according to claim 1 or 2, wherein the concentration of minoxidil in the topical pharmaceutical composition is 5 w / w% or more.

4. A method for inhibiting precipitation derived from minoxidil that occurs after application of an external pharmaceutical composition, comprising adding pyridoxine hydrochloride to the external pharmaceutical composition containing (a) minoxidil, (b) tartaric acid, and (c) 5 to 35 w / w % propylene glycol, The pharmaceutical composition for external application contains 20 w / w % or more of ethanol and 2 to 75 w / w % of water, and does not contain polyethylene glycol; The pH of the pharmaceutical composition for external use after adding pyridoxine hydrochloride is 5.0 to 7.0; The method, wherein the amount of pyridoxine hydrochloride in the topical pharmaceutical composition after adding pyridoxine hydrochloride is 0.05 g per 5 g of minoxidil.

5. 5. The method according to claim 4, wherein pyridoxine hydrochloride is added so that the amount of pyridoxine hydrochloride in the pharmaceutical composition for external application falls within the range of 0.01 to 2 w / w %.

6. The method according to claim 4 or 5, wherein the concentration of minoxidil in the topical pharmaceutical composition is 5 w / w% or more.

7. 1. Use of pyridoxine hydrochloride for inhibiting precipitation derived from minoxidil that occurs after application of an external pharmaceutical composition containing (a) minoxidil, (b) tartaric acid, and (c) 5 to 35 w / w % propylene glycol, The pharmaceutical composition for external application contains 20 w / w % or more of ethanol and 2 to 75 w / w % of water, and does not contain polyethylene glycol; The pH of the pharmaceutical composition for external use after adding pyridoxine hydrochloride is 5.0 to 7.0; The amount of pyridoxine hydrochloride in the topical pharmaceutical composition after adding pyridoxine hydrochloride is 0.05 g per 5 g of minoxidil.

8. 8. The use according to claim 7, wherein pyridoxine hydrochloride is added so that the amount of pyridoxine hydrochloride in the pharmaceutical composition for external application falls within the range of 0.01 to 2 w / w %.

9. The use according to claim 7 or 8, wherein the concentration of minoxidil in the topical pharmaceutical composition is 5 w / w% or more.

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