Topical pharmaceutical composition

Abstract

To provide a minoxidil-containing pharmaceutical composition for external use, since there is a need for a minoxidil-containing preparation to agree with the surface of scalp and spread so that the minoxidil in the minoxidil-containing preparation is efficiently absorbed from the scalp.SOLUTION: A pharmaceutical composition for external use contains (a) minoxidil, (b) at least one selected from the group consisting of urea, cetylpyridinium and a salt thereof, ethyl aminobenzoate, crotamiton and benzethonium and a salt thereof and (c) water. The inventive composition is suitable as liquid chemical, lotion or tonic.SELECTED DRAWING: None

Description

Technical Field

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

Background Art

[0002] Minoxidil is chemically named 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide and is known to be applicable as a hair growth agent (Patent Document 1), and there are many reports of it being a drug that exhibits an excellent hair growth and hair follicle activation effect. The basic performance required for a hair growth agent containing minoxidil is to have excellent absorbability of minoxidil from the scalp (Patent Document 2).

[0003] In order for minoxidil in a formulation containing minoxidil to be efficiently absorbed from the scalp, it is important that the formulation containing minoxidil conforms to and spreads on the surface of the scalp. However, since a formulation containing a large amount of water has 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). Further, Patent Document No. 4 shows that when the concentration of minoxidil increases, the feeling of the formulation spreading on the scalp deteriorates.

[0004] However, none of Patent Documents 1 to 4 above have 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

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

[0006] The present invention aims to provide a minoxidil-containing topical pharmaceutical composition that is easily absorbed by the skin. [Means for solving the problem]

[0007] To solve the above problems, the present invention provides an external pharmaceutical composition containing (a) minoxidil, (b) at least one selected from the group consisting of crotamiton, ethyl aminobenzoate, urea, cetylpyridinium and / or its salts, and benzethonium and / or its salts, and (c) water.

[0008] In other words, the present invention is (1) A topical pharmaceutical composition characterized by containing (a) minoxidil, (b) at least one selected from the group consisting of urea, cetylpyridinium and its salts, ethyl aminobenzoate, crotamiton, and benzethonium and its salts, and (c) water. (2) The topical pharmaceutical composition described in (1), wherein component (b) is urea. (3) The topical pharmaceutical composition according to (1), wherein component (b) is cetylpyridinium and / or a salt thereof. (4) The topical pharmaceutical composition according to (1), wherein component (b) is ethyl aminobenzoate. (5) The topical pharmaceutical composition described in (1), wherein component (b) is crotamiton. (6) The topical pharmaceutical composition according to (1), wherein component (b) is benzethonium and / or a salt thereof. (7)(a) The topical pharmaceutical composition described in (1), wherein the minoxidil content is 3-15 w / v%, (8) A topical pharmaceutical composition according to any one of (1) to (7), further containing a lower alcohol, (9) A topical pharmaceutical composition according to any one of (1) to (8), further containing a polyhydric alcohol. (10) A topical pharmaceutical composition according to any one of (1) to (9), further containing a pH adjuster. (11) The external composition according to (8), wherein the lower alcohol is a lower alcohol having 1 to 5 carbon atoms. (12) The topical pharmaceutical composition 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. (13) The topical pharmaceutical composition according to (10), 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. (14) The external pharmaceutical composition described in (1), wherein the water content is 5 to 75 w / w%, (15) A topical pharmaceutical composition according to any of (1) to (14), wherein the dosage form is a liquid, lotion, or tonic. That is the case. [Effects of the Invention]

[0009] The present invention makes it possible to provide a minoxidil-containing topical pharmaceutical composition with excellent skin compatibility by containing (a) minoxidil, (b) at least one selected from the group consisting of crotamiton, ethyl aminobenzoate, urea, cetylpyridinium and / or its salts, and benzethonium and / or its salts, and (c) water. [Modes for carrying out the invention]

[0010] 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 in the present invention is preferably 1 to 15 w / v% relative to the total amount of the topical pharmaceutical composition. In the topical pharmaceutical composition of the present invention, as the minoxidil content increases, the challenges of skin compatibility also increase; therefore, the higher the concentration of minoxidil in the topical pharmaceutical composition, the greater the significance of implementing the present invention. Specifically, the minoxidil content in the topical pharmaceutical composition of the present invention is more preferably 3 w / v% or more, even more preferably 5 w / v% or more, with an upper limit of 15 w / v% or less, and even more preferably 10 w / v% or less.

[0011] The crotamiton used in this invention can be of a quality commonly used in pharmaceuticals. In this invention, the crotamiton 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.

[0012] The ethyl aminobenzoate of the present invention is sometimes called benzocaine, and a quality commonly used in pharmaceuticals can be used as appropriate. In the present invention, the content of ethyl aminobenzoate 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.

[0013] The urea of ​​the present invention can be of a quality commonly used in pharmaceuticals. In the present invention, the urea 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.

[0014] Examples of the cetylpyridinium and / or its salts of the present invention include cetylpyridinium and cetylpyridinium chloride. Those of the quality usually used in pharmaceuticals can be appropriately used. In the present invention, the content of cetylpyridinium and / or its salts is preferably 0.01 to 2 w / v% in the external pharmaceutical composition of the present invention from the viewpoint of the effects of the present invention, and more preferably 0.04 to 1 w / v%.

[0015] Examples of the benzethonium and / or its salts of the present invention include benzethonium chloride. Those of the quality usually used in pharmaceuticals can be appropriately used. In the present invention, the content of benzethonium and / or its salts is preferably 0.01 to 5 w / v% in the external pharmaceutical composition of the present invention from the viewpoint of the effects of the present invention, and more preferably 0.02 to 0.5 w / v%.

[0016] The water content of the external pharmaceutical composition of the present invention is preferably 1 to 75 w / w% in the external pharmaceutical composition of the present invention from the viewpoint of the effects of the present invention, more preferably 5 to 50 w / w%, still more preferably 8 to 30 w / w%, and most preferably 12 to 30 w / w%. The measurement of the water content in the external pharmaceutical composition of the present invention can be carried out by the Karl Fischer method.

[0017] A pH adjuster can be blended into the external pharmaceutical composition of the present invention as needed. Examples of the pH adjuster include organic acids such as citric acid, malic acid, lactic acid, and tartaric acid, and inorganic acids such as phosphoric acid, hydrochloric acid, and sulfuric acid. The pH of the external pharmaceutical composition of the present invention is preferably adjusted to 5 to 8, more preferably 5.5 to 7.5, and most preferably 6 to 7.

[0018] The external pharmaceutical composition of the present invention can contain a lower alcohol if necessary. As examples of the lower alcohol, those having 1 to 5 carbon atoms are preferred, for example, ethanol, isopropanol, etc. are preferred, and these may be used in combination. The content of the lower alcohol in the external pharmaceutical composition of the present invention is not particularly limited in the present invention, and it may be appropriately prepared and the required amount may be determined. For example, it is preferably 20 w / v% or more in the total composition, more preferably 30 w / v% or more, still more preferably 35 w / v% or more, and still more preferably 50 w / v% or more. The upper limit is more preferably 80 w / v% or less, and still more preferably 70 w / v% or less.

[0019] The external pharmaceutical composition of the present invention can contain a polyhydric alcohol if necessary. Examples of the polyhydric alcohol include 1,3-butylene glycol, dipropylene glycol, propylene glycol, glycerin, polyethylene glycol, etc., and one or a combination of two or more of these may be used. The content of the polyhydric alcohol is not particularly limited in the present invention, and it may be appropriately prepared and the required amount may be determined. For example, it is preferably 5 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 use feeling such as less stickiness.

[0020] In addition to the above-mentioned components, the external pharmaceutical composition of the present invention can contain necessary active ingredients and auxiliary ingredients within a range not impairing the effects of the present invention. Examples of the pharmaceutically active ingredients preferably added and formulated in the external pharmaceutical composition of the present invention include components selected from the group consisting of menthol, vitamin E acetate, hinokitiol, pyridoxine hydrochloride, glycyrrhetinic acid, and diphenhydramine hydrochloride. The addition amounts of these are not particularly restricted, and can be experimentally determined while considering the use feeling, the stability of minoxidil, the solvent system composition, etc.

[0021] 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, benzyl nicotinate, 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, etc.) It can contain commonly used ingredients such as extracts of furan, gardenia, 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, camphor, etc.), and dyes.

[0022] Furthermore, the topical pharmaceutical composition of the present invention is preferably in liquid dosage form and can be a suitable topical pharmaceutical composition such as a liquid, lotion, or tonic.

[0023] The external pharmaceutical composition of the present invention is prepared by a conventional method, by including each of the above-mentioned components.

[0024] The external pharmaceutical composition thus obtained according to the present invention can be used as a skin application preparation such as a hair preparation, eyelash preparation, or eyebrow preparation.

[0025] The present invention will be described in more detail below with reference to examples, comparative examples, and test examples, but the present invention is not limited in any way by these examples. The moisture content of the examples and comparative examples was measured using a Karl Fischer moisture meter. [Examples]

[0026] (Example 1) Minoxidil 5g, crotamiton 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, and dissolved by stirring to obtain an external pharmaceutical composition with a pH of 6.17.

[0027] (Example 2) Minoxidil 5g, ethyl aminobenzoate 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, and dissolved by stirring to obtain an external pharmaceutical composition with a pH of 6.17.

[0028] (Example 3) Minoxidil 5g, urea 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, and dissolved by stirring to obtain an external pharmaceutical composition with a pH of 6.19.

[0029] (Example 4) Minoxidil 5g, cetylpyridinium chloride hydrate 0.2g, 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 with a pH of 6.12.

[0030] (Example 5) Minoxidil 5g, benzethonium chloride 0.5g, 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 stirred to obtain an external pharmaceutical composition with a pH of 6.10.

[0031] (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 with a pH of 6.16.

[0032] (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, and the mixture was stirred to obtain an external pharmaceutical composition with a pH of 6.15.

[0033] Table 1 shows the formulations and pH values ​​of Examples 1-5 and Comparative Examples 1-2 after preparation.

[0034] [Table 1]

[0035] (Skin compatibility evaluation) 100 μL of each test solution from Examples 1-5 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.

[0036] [Formula 1] Skin compatibility improvement rate (%) = (Skin compatibility score of each test solution / Skin compatibility score of Comparative Example 1) × 100

[0037] [Table 2]

[0038] As shown in Table 2, the topical pharmaceutical compositions of Examples 1 to 5 of the present invention showed improved skin compatibility compared to the topical pharmaceutical composition of Comparative Example 1, which did not contain component (b).

[0039] (Example 6) Minoxidil 5g, crotamiton 1g, 1,3-butylene glycol 14g, propylene glycol 15g, purified water 12g, 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 with a pH of 6.75.

[0040] (Example 7) Minoxidil 5g, ethyl aminobenzoate 1g, 1,3-butylene glycol 14g, propylene glycol 15g, purified water 12g, 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 with a pH of 6.76.

[0041] (Example 8) Minoxidil 5g, urea 1g, 1,3-butylene glycol 14g, propylene glycol 15g, purified water 12g, 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 with a pH of 6.77.

[0042] (Example 9) Minoxidil 5g, cetylpyridinium chloride hydrate 0.2g, 1,3-butylene glycol 14g, propylene glycol 15g, purified water 12g, 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 a topical pharmaceutical composition with a pH of 6.70.

[0043] (Example 10) Minoxidil 5g, benzethonium chloride 0.5g, 1,3-butylene glycol 14g, propylene glycol 15g, purified water 12g, 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 with a pH of 6.67.

[0044] (Comparative Example 3) Minoxidil 5g, 1,3-butylene glycol 14g, propylene glycol 15g, purified water 12g, 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 with a pH of 6.77.

[0045] (Comparative Example 4) Minoxidil 5g, panthenol 1g, 1,3-butylene glycol 14g, propylene glycol 15g, purified water 12g, 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 with a pH of 6.75.

[0046] Table 3 shows the formulations and pH values ​​of Examples 6-10 and Comparative Examples 3-4 after preparation.

[0047] [Table 3]

[0048] (Skin compatibility evaluation) 100 μL of each test solution from Examples 6-10 and Comparative Examples 3-4 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 4.

[0049] [Formula 2] Skin compatibility improvement rate (%) = (Skin compatibility score of each test solution / Skin compatibility score of Comparative Example 3) × 100

[0050] [Table 4]

[0051] As shown in Table 4, the topical pharmaceutical compositions of Examples 6 to 10 of the present invention showed improved skin compatibility compared to the topical pharmaceutical composition of Comparative Example 3, which did not contain component (b).

[0052] (Example 11) Minoxidil 5g, crotamiton 1g, 1,3-butylene glycol 1g, glycerin 12g, ethanol 55g, appropriate amounts of lactic acid and citric 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 with a pH of 6.93.

[0053] (Example 12) Minoxidil 5g, ethyl aminobenzoate 1g, 1,3-butylene glycol 1g, glycerin 12g, ethanol 55g, appropriate amounts of lactic acid and citric 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 with a pH of 6.93.

[0054] (Example 13) Minoxidil 5g, urea 1g, 1,3-butylene glycol 1g, glycerin 12g, ethanol 55g, appropriate amounts of lactic acid and citric 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 with a pH of 6.94.

[0055] (Example 14) Minoxidil 5g, cetylpyridinium chloride hydrate 0.2g, 1,3-butylene glycol 1g, glycerin 12g, ethanol 55g, appropriate amounts of lactic acid and citric 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 with a pH of 6.86.

[0056] (Example 15) Minoxidil 5g, benzethonium chloride 0.5g, 1,3-butylene glycol 1g, glycerin 12g, ethanol 55g, appropriate amount of lactic acid, appropriate amount of citric 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 with a pH of 6.85.

[0057] (Comparative Example 5) Minoxidil 5g, 1g 1,3-butylene glycol, glycerin 12g, ethanol 55g, appropriate amounts of lactic acid and citric acid, and purified water were mixed to make a total volume of 100mL, and stirred to dissolve and obtain an external pharmaceutical composition with a pH of 6.90.

[0058] (Comparative Example 6) Minoxidil 5g, panthenol 1g, 1,3-butylene glycol 1g, glycerin 12g, ethanol 55g, appropriate amounts of lactic acid and citric 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 with a pH of 6.91.

[0059] Table 5 shows the formulations and pH values ​​of Examples 11-15 and Comparative Examples 5-6 after preparation.

[0060] [Table 5]

[0061] (Skin compatibility evaluation) 100 μL of each test solution from Examples 11-15 and Comparative Examples 5-6 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 6.

[0062] [Formula 3] Skin compatibility improvement rate (%) = (Skin compatibility score of each test solution / Skin compatibility score of Comparative Example 5) × 100

[0063] [Table 6]

[0064] As shown in Table 6, the topical pharmaceutical compositions of Examples 11 to 15 of the present invention showed improved skin compatibility compared to the topical pharmaceutical composition of Comparative Example 5, which did not contain component (b).

[0065] (Example 16) Minoxidil 5g, crotamiton 1g, 1,3-butylene glycol 10g, purified water 17g, 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 with a pH of 6.08.

[0066] (Example 17) Minoxidil 5g, ethyl aminobenzoate 1g, 1,3-butylene glycol 10g, purified water 17g, 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 with a pH of 6.09.

[0067] (Example 18) Minoxidil 5g, urea 1g, 1,3-butylene glycol 10g, purified water 17g, 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 with a pH of 6.09.

[0068] (Example 19) Minoxidil 5g, cetylpyridinium chloride hydrate 0.2g, 1,3-butylene glycol 10g, purified water 17g, 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 a topical pharmaceutical composition with a pH of 6.04.

[0069] (Example 20) Minoxidil 5g, benzethonium chloride 0.5g, 1,3-butylene glycol 10g, purified water 17g, an appropriate amount of phosphoric acid, and ethanol were mixed to a total volume of 100mL and stirred to obtain an external pharmaceutical composition with a pH of 6.02.

[0070] (Comparative Example 7) Minoxidil 5g, 10g 1,3-butylene glycol, 17g 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 obtain an external pharmaceutical composition with a pH of 6.05.

[0071] (Comparative Example 8) Minoxidil 5g, panthenol 1g, 1,3-butylene glycol 10g, purified water 17g, an appropriate amount of phosphoric acid, and ethanol were mixed to a total volume of 100mL and stirred to obtain an external pharmaceutical composition with a pH of 6.08.

[0072] Table 7 shows the formulations and pH values ​​of Examples 16-20 and Comparative Examples 7-8 after preparation.

[0073] [Table 7]

[0074] (Skin compatibility evaluation) 100 μL of each test solution from Examples 16-20 and Comparative Examples 7-8 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 4] below. The calculated results are shown in Table 8.

[0075] [Formula 4] Skin compatibility improvement rate (%) = (Skin compatibility score of each test solution / Skin compatibility score of Comparative Example 7) × 100

[0076] [Table 8]

[0077] As shown in Table 8, the topical pharmaceutical compositions of Examples 16 to 20 of the present invention showed improved skin compatibility compared to the topical pharmaceutical composition of Comparative Example 7, which did not contain component (b).

[0078] Furthermore, as an external composition of another invention, 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%, 1,3-butylene One example is a formulation containing 2-30 w / v glycol, 1-30 w / v glycerin, 20-80 w / v ethanol, 0.001-1 w / v antioxidant (dibutylhydroxytoluene, dibutylhydroxyanisole, sodium pyrosulfate, sodium edetate, or pyropyr gallate), an appropriate amount of phosphoric acid, 0.00001-1 w / v glycine, 0.00001-1 w / v L-arginine, and 0.000001-1 w / v ascorbic acid, with the remainder prepared by adding water. These active and auxiliary components 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 9.

[0079] [Table 9]

[0080] Furthermore, as an external composition of another invention, 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%, crotamiton 1-5 w / v%, ethyl aminobenzoate 0.5-5 w / v%, urea 1-5 w / v%, cetiripyridinium and / or so One example is a formulation containing 0.04-0.2 w / v% of a salt of minoxidil, 0.05-0.5 w / v% of benzethonium and / or its salt, 2-30 w / v% of 1,3-butylene glycol, 1-30 w / v% of glycerin, 20-70 w / v% of ethanol, 0.001-1 w / v% of an antioxidant (dibutylhydroxytoluene, dibutylhydroxyanisole, sodium pyrosulfate, sodium edetate, or pyropyr gallate), an appropriate amount of phosphoric acid, 0.00001-1 w / v% of glycine, 0.00001-1 w / v% of L-arginine, and 0.000001-1 w / v% of ascorbic acid, with the remainder prepared by adding water. 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.

[0081] [Table 10]

Claims

1. (a) 3-15 w / v% minoxidil, (b) 0.1-5 w / v% urea, (c) water, (d) lower alcohol, and (e) polyhydric alcohol, A topical pharmaceutical composition characterized in that 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, and the dosage form is a liquid, lotion, or tonic.

2. The topical pharmaceutical composition according to claim 1, further comprising a pH adjuster.

3. The topical pharmaceutical composition according to claim 1 or 2, wherein the lower alcohol is a lower alcohol having 1 to 5 carbon atoms.

4. The topical pharmaceutical composition according to claim 2, 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.

5. The topical pharmaceutical composition according to claim 1, wherein the water content is 5 to 75 w / w%.

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