Topical pharmaceutical composition

Abstract

For minoxidil in a minoxidil-containing formulation to be efficiently absorbed through the scalp, it is important that the formulation blends well with and spreads across the surface of the scalp. In other words, the object of the present invention is to provide a minoxidil-containing topical pharmaceutical composition that blends well with the skin. [Solution] The present invention is a topical pharmaceutical composition containing (a) 5 w / v% or more of minoxidil, (b) benzalkonium and / or a salt thereof, and (c) water. The present invention is suitably used as a liquid, lotion, or tonic.

Description

Technical Field

[0001] The present invention relates to an external pharmaceutical composition containing minoxidil.

[0002] Minoxidil is known as 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide in chemical name and is known to be applicable as a hair growth agent (Patent Document 1), and there are many reports as an agent that exhibits an excellent hair growth and hair follicle activation effect. The basic performance required for a hair growth agent containing minoxidil is to be excellent in the absorbability of minoxidil from the scalp (Patent Document 2). In order for minoxidil in a preparation containing minoxidil to be efficiently absorbed from the scalp, it is preferable that minoxidil in the preparation exists in a dissolved state and no crystals or the like are formed. And it is important that the preparation containing minoxidil conforms to and spreads on the surface of the scalp. However, since a preparation containing a large amount of water has a surface free energy acting between it and hydrophobic skin, it maintains a droplet state and is difficult to spread on the skin surface. As a technique for improving skin conformity, for example, a method using polyether-modified silicone or polyglycerol-modified silicone, and sucrose fatty acid ester has been proposed (Patent Document 3). Also, Patent Document 4 shows that when the concentration of minoxidil increases, the feeling of the preparation spreading on the scalp deteriorates. However, none of Patent Documents 1 to 4 above has a description suggesting the adoption of the configuration of the present invention in order to obtain the present invention which is an external pharmaceutical composition containing minoxidil with good skin conformity.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

[0004] The present invention aims to provide a minoxidil-containing topical pharmaceutical composition that is easily absorbed by the skin. [Means for solving the problem]

[0005] To solve the above problems, the present invention provides an external pharmaceutical composition containing (a) 5 w / v% or more of minoxidil, (b) at least one selected from camphor, benzyl nicotinate, chlorpheniramine maleate, benzalkonium and / or salts thereof, and (c) water. In other words, the present invention is (1) A topical pharmaceutical composition characterized by containing (a) 5 w / v% or more of minoxidil, (b) at least one selected from the group consisting of camphor, benzyl nicotinate, chlorpheniramine maleate, benzalkonium and / or salts thereof, and (c) water. (2)(a) The topical pharmaceutical composition according to (1), wherein the minoxidil content is 5-15 w / v%. (3) The topical pharmaceutical composition according to (1) or (2), further containing a lower alcohol. (4) A topical pharmaceutical composition according to any one of (1) to (3), further containing a polyhydric alcohol, (5) A topical pharmaceutical composition according to any one of (1) to (4), further containing a pH adjuster. (6) The topical pharmaceutical composition described in (3), wherein the lower alcohol is a lower alcohol having 1 to 5 carbon atoms. (7) The topical pharmaceutical composition according to (4), 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. (8) The topical pharmaceutical composition according to (5), wherein the pH adjusting agent is at least one selected from the group consisting of citric acid, malic acid, lactic acid, tartaric acid, phosphoric acid, hydrochloric acid, and sulfuric acid. (9) The external pharmaceutical composition described in (1), wherein the water content is 5 to 75 w / w%, (10) A topical pharmaceutical composition according to any one of (1) to (9), wherein the dosage form is a liquid, lotion, tonic, gel, or aerosol. (11) For the manufacture of a topical pharmaceutical composition containing 5 w / v% or more of minoxidil, use of at least one selected from the group consisting of camphor, benzyl nicotinate, chlorpheniramine maleate, benzalkonium and / or salts thereof, (12) To improve the skin compatibility of topical pharmaceutical compositions containing 5 w / v% or more minoxidil, use of at least one selected from the group consisting of camphor, benzyl nicotinate, chlorpheniramine maleate, benzalkonium and / or salts thereof. That is the case. [Effects of the Invention]

[0006] The present invention makes it possible to provide a minoxidil-containing topical pharmaceutical composition with excellent skin compatibility by combining (a) 5 w / v% or more of minoxidil, (b) at least one selected from the group consisting of camphor, benzyl nicotinate, chlorpheniramine maleate, benzalkonium and / or salts thereof, and (c) water. [Modes for carrying out the invention]

[0007] The minoxidil used in the topical pharmaceutical composition of the present invention can be of a quality commonly used in pharmaceuticals. Furthermore, the minoxidil content used in the present invention is 5 w / v% or more relative to the total topical pharmaceutical composition, which would significantly increase the risk of skin absorption. Specifically, 5 to 15 w / v% is preferred, and more preferably 5 to 10 w / v%.

[0008] The camphor used in this invention is of a quality commonly used in pharmaceuticals and can be used as appropriate. In this invention, the camphor content in the topical pharmaceutical composition of this invention is preferably 0.01 to 10 w / v%, and more preferably 0.1 to 5 w / v%, from the viewpoint of the effects of this invention.

[0009] The benzyl nicotinate used in the present invention can be of a quality commonly used in pharmaceuticals. In the present invention, the benzyl nicotinate content in the topical pharmaceutical composition of the present invention is preferably 0.01 to 10 w / v%, and more preferably 0.1 to 5 w / v%, from the viewpoint of the effects of the present invention.

[0010] The chlorpheniramine maleate of the present invention can be of a quality commonly used in pharmaceuticals. In the present invention, the content of chlorpheniramine maleate in the topical pharmaceutical composition of the present invention is preferably 0.01 to 10 w / v%, and more preferably 0.05 to 5 w / v%, from the viewpoint of the effects of the present invention.

[0011] Examples of benzalkonium and / or its salts in the present invention include benzalkonium chloride. The benzalkonium and / or its salts in the present invention can be of a quality commonly used in pharmaceuticals. In the present invention, the content of benzalkonium and / or its salts in the topical pharmaceutical composition of the present invention is preferably 0.001 to 2 w / v%, and more preferably 0.01 to 1 w / v%, from the viewpoint of the effects of the present invention.

[0012] From the viewpoint of the effects of the present invention, the water content in the topical pharmaceutical composition of the present invention is preferably 1 to 75 w / w%, more preferably 5 to 50 w / w%, even more preferably 8 to 30 w / w%, and most preferably 15 to 30 w / w%. The water content in the topical pharmaceutical composition of the present invention can be measured by the Karl Fischer method.

[0013] The external pharmaceutical composition of the present invention can be formulated with a pH adjuster if necessary. Examples of the pH adjuster include organic acids such as citric acid, malic acid, lactic acid, tartaric acid, and inorganic acids such as phosphoric acid, hydrochloric acid, sulfuric acid. The pH of the external pharmaceutical composition of the present invention is preferably adjusted to 5 to 8, more preferably 5.6 to 7.

[0014] The external pharmaceutical composition of the present invention can be formulated with a lower alcohol if necessary. Examples of the lower alcohol preferably have 1 to 5 carbon atoms, and for example, ethanol, isopropanol, etc. are preferred. Two or more kinds of lower alcohols may be used in combination. The content of the lower alcohol in the external pharmaceutical composition of the present invention is preferably 20 w / v% or more, more preferably 30 w / v% or more, still more preferably 35 w / v% or more, and still more preferably 50 w / v% or more in the whole composition. The upper limit is preferably 80 w / v%.

[0015] The external pharmaceutical composition of the present invention can be formulated with a polyhydric alcohol if necessary. Examples of the polyhydric alcohol include 1,3-butylene glycol, dipropylene glycol, propylene glycol, glycerin, polyethylene glycol, etc. Preferred are 1,3-butylene glycol, propylene glycol, glycerin, and more preferred is 1,3-butylene glycol. These may be used alone or in combination of two or more. The content of the polyhydric alcohol is preferably 3 w / v% or more, more preferably 5 w / v% or more, more preferably 8 w / v% or more, more preferably 10 w / v% or more in the external pharmaceutical composition of the present invention, and the upper limit is preferably 30 w / v% or less considering the feeling of use such as less stickiness.

[0016] The external pharmaceutical composition of the present invention can further be formulated with a surfactant if necessary. However, since the addition of the surfactant may affect the feeling of use and the skin absorption of minoxidil, it is preferably substantially free of the surfactant.

[0017] In addition to the components described above, the topical pharmaceutical composition of the present invention may contain active ingredients and auxiliary ingredients as needed, provided that the effects of the present invention are not impaired. Preferred pharmacoactive ingredients to be added to the topical pharmaceutical composition of the present invention include one or more ingredients selected from the group consisting of menthol, vitamin E acetate, hinokitiol, pyridoxine hydrochloride, glycyrrhetinic acid, and diphenhydramine hydrochloride. The amounts of these ingredients added are not particularly restricted and can be determined experimentally, taking into consideration factors such as the feel of use, the stability of minoxidil, and the solvent system composition.

[0018] In addition to the above-mentioned components, the topical pharmaceutical composition of the present invention may contain various active ingredients and auxiliary components commonly used in topical preparations, as long as they do not impair the effects of the present invention. For example, excipients, hair growth ingredients (6-benzylaminopurine, adenosine, pentadecanoic acid glyceride, He Shou Bird, etc.), vasodilators (carpronium chloride, Swertia japonica extract, Panax ginseng extract, Panax ginseng tincture, Capsicum tincture, etc.), antihistamines (isotipendyl hydrochloride, etc.), anti-inflammatory agents (guaiazulene, etc.), keratolytic agents (salicylic acid, etc.), antiseptics (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, piroctone olamine, etc.), humectants (hyaluronic acid or its salts, chondroitin sulfate, etc.), various plants and animals (yew, peony bark, licorice, St. John's wort, aconite, loquat, Artemisia capillaris, comfrey, Angelica keiskei, saffron) It can contain extracts of gardenia fruit, rosemary, sage, Banksia japonica, Western Banksia japonica, hops, placenta, saw palmetto, pumpkin seed, etc., vitamins (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, cooling agents (peppermint oil, etc.), dyes, and other commonly used ingredients.

[0019] Furthermore, the topical pharmaceutical composition of the present invention is preferably in a liquid dosage form, and can be made into appropriate topical pharmaceutical compositions such as solutions, lotions, tonics, gels, aerosols, etc., and preferably solutions, lotions, tonics.

[0020] The preparation of the topical pharmaceutical composition of the present invention is prepared by containing each of the above components according to a conventional method.

[0021] The thus obtained topical pharmaceutical composition of the present invention can be used as a skin application preparation such as a hair preparation, an eyelash preparation, an eyebrow preparation, etc.

[0022] Examples, comparative examples, reference examples, and test examples are described below to further specifically explain the present invention, but the present invention is not limited in any way by these examples. The moisture content of the examples, comparative examples, and reference examples was measured using a Karl Fischer moisture meter.

Examples

[0023] (Example 1) 5 g of minoxidil, 1 g of dl-camphor, 10 g of 1,3-butylene glycol, 60 g of ethanol, an appropriate amount of phosphoric acid, and the total amount was made up to 100 mL with purified water, and stirred and dissolved to obtain a topical pharmaceutical composition (solution) with a pH of 6.17.

[0024] (Example 2) 5 g of minoxidil, 0.125 g of benzyl nicotinate, 10 g of 1,3-butylene glycol, 60 g of ethanol, an appropriate amount of phosphoric acid, and the total amount was made up to 100 mL with purified water, and stirred and dissolved to obtain a topical pharmaceutical composition (solution) with a pH of 6.15.

[0025] (Example 3) 5 g of minoxidil, 1 g of chlorpheniramine maleate, 10 g of 1,3-butylene glycol, 60 g of ethanol, an appropriate amount of phosphoric acid, and the total amount was made up to 100 mL with purified water, and stirred and dissolved to obtain a topical pharmaceutical composition (solution) with a pH of 6.05.

[0026] (Example 4) Minoxidil 5g, benzalkonium chloride 0.3g, 1,3-butylene glycol 10g, ethanol 60g, an appropriate amount of phosphoric acid, and purified water were mixed to make a total volume of 100mL, and the mixture was stirred to dissolve and obtain an external pharmaceutical composition (liquid) with a pH of 6.12.

[0027] (Comparative Example 1) Minoxidil 5g, 10g 1,3-butylene glycol, 60g ethanol, an appropriate amount of phosphoric acid, and purified water were mixed to make a total volume of 100mL, and the mixture was stirred to obtain an external pharmaceutical composition (liquid) with a pH of 6.16.

[0028] (Comparative Example 2) Minoxidil 5g, panthenol 1g, 1,3-butylene glycol 10g, ethanol 60g, an appropriate amount of phosphoric acid, and purified water were mixed to make a total volume of 100mL, which was then stirred to obtain an external pharmaceutical composition (liquid) with a pH of 6.15.

[0029] Table 1 shows the formulations, water content, and pH of Examples 1-4 and Comparative Examples 1-2 after preparation.

[0030] [Table 1]

[0031] (Skin compatibility evaluation) 100 μL of each test solution from Examples 1-4 and Comparative Examples 1-2 was measured using a micropipette (Eppendorf) and dropped onto a BioSkin plate (#40, Beulux). After 30 seconds, the long and short diameters of the spread solution were measured, and the product of these values ​​was used as the skin compatibility score. The skin compatibility improvement rate was calculated according to [Formula 1] below. The calculated results are shown in Table 2. [Formula 1] Skin compatibility improvement rate (%) = (Skin compatibility score of each test solution / Skin compatibility score of Comparative Example 1) × 100

[0032] [Table 2] As shown in Table 2, the topical pharmaceutical compositions of Examples 1 to 4 of the present invention showed improved skin compatibility compared to the topical pharmaceutical composition of Comparative Example 1, which did not contain component (b).

[0033] (Reference example 1) Minoxidil 1g, 10g 1,3-butylene glycol, 60g ethanol, an appropriate amount of phosphoric acid, and purified water were mixed to make a total volume of 100mL, and the mixture was stirred to obtain an external pharmaceutical composition (liquid) with a pH of 5.81. (Reference example 2) Minoxidil 5g, 10g 1,3-butylene glycol, 60g ethanol, an appropriate amount of phosphoric acid, and purified water were mixed to make a total volume of 100mL, which was then stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.13.

[0034] Table 3 shows the formulations for Reference Examples 1 and 2, as well as the water content and pH after preparation.

[0035] [Table 3]

[0036] The results of evaluating the skin compatibility of Reference Example 1 and Reference Example 2 showed that the skin compatibility score for Reference Example 2 was 88%, which is lower than that of Reference Example 1. This indicates that the higher the concentration of minoxidil, the worse the skin compatibility.

[0037] (Example 5) Minoxidil 5g, dl-camphor 1g, 1,3-butylene glycol 14g, propylene glycol 14g, purified water 13g, an appropriate amount of tartaric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.75.

[0038] (Example 6) Minoxidil 5g, benzyl nicotinate 0.125g, 1,3-butylene glycol 14g, propylene glycol 14g, purified water 13g, an appropriate amount of tartaric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.75.

[0039] (Example 7) Minoxidil 5g, chlorpheniramine maleate 1g, 1,3-butylene glycol 14g, propylene glycol 14g, purified water 13g, an appropriate amount of tartaric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.61.

[0040] (Example 8) Minoxidil 5g, benzalkonium chloride 0.3g, 1,3-butylene glycol 14g, propylene glycol 14g, purified water 13g, an appropriate amount of tartaric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.69.

[0041] (Comparative Example 3) Minoxidil 5g, 1,3-butylene glycol 14g, propylene glycol 14g, purified water 13g, an appropriate amount of tartaric acid, and ethanol were mixed to make a total volume of 100mL, and the mixture was stirred to dissolve and obtain an external pharmaceutical composition (liquid) with a pH of 6.75.

[0042] (Comparative Example 4) Minoxidil 5g, pantothenyl ethyl ether 1g, 1,3-butylene glycol 14g, propylene glycol 14g, purified water 13g, an appropriate amount of tartaric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.75.

[0043] (Comparative Example 5) Minoxidil 5g, panthenol 1g, 1,3-butylene glycol 14g, propylene glycol 14g, purified water 13g, an appropriate amount of tartaric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.76.

[0044] Table 4 shows the formulations, water content, and pH of Examples 5-8 and Comparative Examples 3-5 after preparation.

[0045] [Table 4]

[0046] (Skin compatibility evaluation) 100 μL of each test solution from Examples 5-8 and Comparative Examples 3-5 was measured using a micropipette (Eppendorf) and dropped onto a BioSkin plate (#40, Beulux). After 30 seconds, the long and short diameters of the spread solution were measured, and the product of these values ​​was used as the skin compatibility score. The skin compatibility improvement rate was calculated according to [Equation 2] below. The calculated results are shown in Table 5. [Formula 2] Skin compatibility improvement rate (%) = (Skin compatibility score of each test solution / Skin compatibility score of Comparative Example 3) × 100

[0047] [Table 5] As shown in Table 5, the topical pharmaceutical compositions of Examples 5 to 8 of the present invention showed improved skin compatibility compared to the topical pharmaceutical composition of Comparative Example 3, which did not contain component (b).

[0048] (Example 9) Minoxidil 5g, dl-camphor 1g, 1,3-butylene glycol 1g, glycerin 13g, purified water 12g, appropriate amounts of lactic acid and citric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 7.02.

[0049] (Example 10) Minoxidil 5g, benzyl nicotinate 0.125g, 1,3-butylene glycol 1g, glycerin 13g, purified water 12g, appropriate amounts of lactic acid and citric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 7.03.

[0050] (Example 11) Minoxidil 5g, chlorpheniramine maleate 1g, 1,3-butylene glycol 1g, glycerin 13g, purified water 12g, appropriate amounts of lactic acid and citric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.85.

[0051] (Example 12) Minoxidil 5g, benzalkonium chloride 0.3g, 1,3-butylene glycol 1g, glycerin 13g, purified water 12g, appropriate amounts of lactic acid and citric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.91.

[0052] (Comparative Example 6) Minoxidil 5g, 1g 1,3-butylene glycol, 13g glycerin, 12g purified water, appropriate amounts of lactic acid and citric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.99.

[0053] (Comparative Example 7) Minoxidil 5g, pantothenyl ethyl ether 1g, 1,3-butylene glycol 1g, glycerin 13g, purified water 12g, appropriate amounts of lactic acid and citric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 7.03.

[0054] (Comparative Example 8) Minoxidil 5g, panthenol 1g, 1,3-butylene glycol 1g, glycerin 13g, purified water 12g, appropriate amounts of lactic acid and citric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 7.05.

[0055] Table 6 shows the formulations, water content, and pH of Examples 9-12 and Comparative Examples 6-8 after preparation.

[0056] [Table 6]

[0057] (Skin compatibility evaluation) 100 μL of each test solution from Examples 9-12 and Comparative Examples 6-8 was measured using a micropipette (Eppendorf) and dropped onto a BioSkin plate (#40, Beulux). After 30 seconds, the long and short diameters of the spread solution were measured, and the product of these values ​​was used as the skin compatibility score. The skin compatibility improvement rate was calculated according to [Equation 3] below. The calculated results are shown in Table 7. [Formula 3] Skin compatibility improvement rate (%) = (Skin compatibility score of each test solution / Skin compatibility score of Comparative Example 6) × 100

[0058] [Table 7] As shown in Table 7, the topical pharmaceutical compositions of Examples 9 to 12 of the present invention showed improved skin compatibility compared to the topical pharmaceutical composition of Comparative Example 6, which did not contain component (b).

[0059] (Example 13) Minoxidil 5g, dl-camphor 1g, 1,3-butylene glycol 10g, purified water 15g, an appropriate amount of phosphoric acid, and ethanol were mixed to make a total volume of 100mL, and the mixture was stirred to dissolve and obtain an external pharmaceutical composition (liquid) with a pH of 6.11.

[0060] (Example 14) Minoxidil 5g, benzyl nicotinate 0.125g, 1,3-butylene glycol 10g, purified water 15g, an appropriate amount of phosphoric acid, and ethanol were mixed to make a total volume of 100mL. Dissolved by stirring, a topical pharmaceutical composition (liquid) with a pH of 6.10 was obtained.

[0061] (Example 15) Minoxidil 5g, chlorpheniramine maleate 1g, 1,3-butylene glycol 10g, purified water 15g, an appropriate amount of phosphoric acid, and ethanol were mixed to make a total volume of 100mL. The mixture was stirred and dissolved to obtain an external pharmaceutical composition (liquid) with a pH of 6.00.

[0062] (Example 16) Minoxidil 5g, benzalkonium chloride 0.3g, 1,3-butylene glycol 10g, purified water 15g, an appropriate amount of phosphoric acid, and ethanol were mixed to make a total volume of 100mL, and the mixture was stirred to dissolve and obtain an external pharmaceutical composition (liquid) with a pH of 6.05.

[0063] (Comparative Example 9) Minoxidil 5g, 10g 1,3-butylene glycol, 15g purified water, an appropriate amount of phosphoric acid, and ethanol were mixed to make a total volume of 100mL, and the mixture was stirred to dissolve and obtain an external pharmaceutical composition (liquid) with a pH of 6.10.

[0064] (Comparative Example 10) Minoxidil 5g, pantothenyl ethyl ether 1g, 1,3-butylene glycol 10g, purified water 15g, an appropriate amount of phosphoric acid, and ethanol were mixed to make a total volume of 100mL, and the mixture was stirred to dissolve and obtain an external pharmaceutical composition (liquid) with a pH of 6.09.

[0065] (Comparative Example 11) Minoxidil 5g, panthenol 1g, 1,3-butylene glycol 10g, purified water 15g, an appropriate amount of phosphoric acid, and ethanol were mixed to make a total volume of 100mL, and the mixture was stirred to dissolve and obtain an external pharmaceutical composition (liquid) with a pH of 6.11.

[0066] Table 8 shows the formulations, water content, and pH of Examples 13-16 and Comparative Examples 9-11 after preparation.

[0067] [Table 8]

[0068] (Skin compatibility evaluation) 100 μL of each test solution from Examples 13-16 and Comparative Examples 9-11 was measured using a micropipette (Eppendorf) and dropped onto a BioSkin plate (#40, Beulux). After 30 seconds, the long and short diameters of the spread solution were measured, and the product of these values ​​was used as the skin compatibility score. The skin compatibility improvement rate was calculated according to [Equation 4] below. The calculated results are shown in Table 9. [Formula 4] Skin compatibility improvement rate (%) = (Skin compatibility score of each test solution / Skin compatibility score of Comparative Example 9) × 100

[0069] [Table 9] As shown in Table 9, the topical pharmaceutical compositions of Examples 13 to 16 of the present invention showed improved skin compatibility compared to the topical pharmaceutical composition of Comparative Example 9, which did not contain component (b).

[0070] Furthermore, as another embodiment of the topical composition, for example, minoxidil 0.1-10 w / v%, menthol 0.1-5 w / v% as an active ingredient or auxiliary ingredient, vitamin E acetate 0.001-1 w / v%, pyridoxine hydrochloride 0.001-1 w / v%, hinokitiol 0.001-1 w / v%, glycyrrhetinic acid 0.001-1 w / v%, diphenhydramine hydrochloride 0.001-1 w / v%, pantothenyl ethyl ether or panthenol 0.1-5 w / v%, dl-camphor 0.1-1 w / v%, benzyl nicotinate 0.01-0.125 w / v%, chlorpheniramine maleate 0 A formulation containing 0.05-1 w / v%, benzalkonium and / or its salt 0.02-0.3 w / v%, 1,3-butylene glycol 2-30 w / v%, glycerin 1-30 w / v%, ethanol 20-70 w / v%, antioxidant (dibutylhydroxytoluene, dibutylhydroxyanisole, sodium pyrosulfate, sodium edetate, or pyropyr gallate) 0.001-1 w / v%, an appropriate amount of phosphoric acid, glycine 0.00001-1 w / v%, L-arginine 0.00001-1 w / v%, and ascorbic acid 0.000001-1 w / v%, with the remainder prepared by adding water, is one example. These active ingredients and auxiliary ingredients can be added as appropriate, taking into consideration the feel of use, the stability of minoxidil, or the solvent system composition. An example formulation of this topical composition is shown in Table 10.

[0071] [Table 10] [Industrial applicability]

[0072] This invention makes it possible to provide a minoxidil-containing topical pharmaceutical composition that is easily absorbed by the skin.

Claims

1. (a) Minoxidil at 5 w / v% or higher, (b) benzalkonium and / or salts thereof, (c) 8-30 w / w% water, (d) Lower alcohols, (e) 10-30 w / v% polyhydric alcohols, (f) pH adjuster A topical pharmaceutical composition characterized by containing [a specific ingredient].

2. (a) The topical pharmaceutical composition according to claim 1, wherein the minoxidil content is 5 to 15 w / v%.

3. The topical pharmaceutical composition according to Claim 1, wherein the lower alcohol is a lower alcohol having 1 to 5 carbon atoms.

4. The topical pharmaceutical composition according to claim 1, 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.

5. The topical pharmaceutical composition according to claim 1, wherein the pH adjusting agent is at least one selected from the group consisting of citric acid, malic acid, lactic acid, tartaric acid, phosphoric acid, hydrochloric acid, and sulfuric acid.

6. The topical pharmaceutical composition according to any one of claims 1 to 5, wherein the dosage form is a liquid, a lotion, or a tonic.