JP6424815B2 - Composition for external use - Google Patents

Description

  The present invention relates to a cream containing minoxidil. More specifically, the present invention relates to a minoxidil-containing cream excellent in stability and feeling of use of the preparation.

Minoxidil is referred to as the chemical name 6- (1-piperidinyl) -2,4-pyrimidinediamine-3-oxide, and its application as a hair growth agent is known (see Patent Document 1). Minoxidil is a drug that exerts excellent hair growth and hair growth effects by external application, and a lotion-type minoxidil-containing external preparation is commercially available at home and abroad.
However, lotion type formulations are concerned that dripping may occur during use. Therefore, although a minoxidil-containing external application composition without dripping is desired, it is a fact that a minoxidil-containing external composition with dripping suppression has not yet been provided.
On the other hand, minoxidil hardly dissolves in water and easily dissolves in alcohol. Therefore, a minoxidil-containing external composition commercially available at home and abroad contains a large amount of alcohol. Therefore, a less irritating minoxidil-containing product that can be used safely by people who are sensitive to alcohol is desired.
Although a semisolid preparation such as a cream may be considered as a preparation capable of suppressing liquid dripping, it contains minoxidil in a soluble form without containing a lower alcohol, and the preparation is stable and the feeling in use is low and mild. Nothing is known about creams.

U.S. Pat. No. 4,139,619.

  An object of the present invention is to provide a minoxidil-containing external composition which can dissolve minoxidil without containing a lower alcohol, is stable, has a good feeling in use, and has a mildness, with respect to a minoxidil-containing cream.

  As a result of intensive studies to solve the above problems, the present inventors have found that minoxidil, a cream containing a specific amount of a higher fatty acid and / or a salt thereof, a thickener and a surfactant usually dissolves minoxidil. It has been found that it is possible to dissolve minoxidil without containing a large amount of lower alcohol necessary for causing the reaction, which is stable and excellent in feeling upon use, and the present invention has been completed.

That is, the present invention
(1) Minoxidil, characterized in that it contains 1.5 parts by mass or more of a higher fatty acid and / or a salt thereof, a thickener and a surfactant per 1 part by mass of minoxidil, and substantially does not contain a lower alcohol Cream,
(2) The cream according to (1), wherein the higher fatty acid is isostearic acid and / or oleic acid
(3) The cream according to (1), wherein the thickener is a carboxyvinyl polymer.
(4) The cream according to (1), wherein the surfactant is a nonionic surfactant
(5) The cream according to any one of claims 1 to 4, further comprising a polyhydric alcohol.
(6) The cream according to (5), wherein the polyhydric alcohol is one or more selected from the group consisting of 1,3-butylene glycol, dipropylene glycol, glycerin and propylene glycol.
(7) The cream according to any one of (1) to (6), which has a pH of 5 to 8,
It is.

  According to the present invention, it is possible to provide a minoxidil-containing cream which can dissolve minoxidil without containing a large amount of lower alcohol causing skin irritation which has been required so far and which is excellent in stability and feeling in use. It became possible.

  As the minoxidil used in the present invention, one having a quality generally used for pharmaceuticals can be appropriately used. The content of minoxidil in the cream of the present invention is 0.1 to 10 w / w%, preferably 0.2 to 5 w / w%, and more preferably 1 to 5 w / w%.

  As the higher fatty acids and / or salts thereof used in the present invention, those having 10 to 22 carbon atoms are preferable. For example, isostearic acid, oleic acid, stearic acid, capric acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, linole Examples of the acid include linolenic acid, elaidic acid, arachidic acid, arachidonic acid, behenic acid, eicosapentaenoic acid, docosaexaenoic acid and the like. Among these, those having 18 carbon atoms are preferable, and isostearic acid or oleic acid is particularly preferable. These higher fatty acids and / or their salts may be used in combination. Examples of salts include metal salts such as sodium salt, potassium salt, lithium salt, magnesium salt and calcium salt; ammonium salts such as ammonium salt and alkyl ammonium salt; monoethanolamine salt, diethanolamine salt, triethanolamine salt, aminomethylpropanol Examples include alkanolamine salts such as salts; basic amino acid salts such as lysine salts and arginine salts, and choline salts. From the viewpoint of the effect of the present invention, the content of the higher fatty acid and / or the salt thereof is required to be 1.5 parts by mass or more, preferably 3 parts by mass or more, with respect to 1 part by mass of minoxidil. Moreover, as content of the higher fatty acid and / or its salt contained in the cream agent of this invention, it is 0.3-30 w / w%, Preferably it is 1.5-30 w / w%.

  Examples of the thickener in the present invention include carboxyvinyl polymers, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, ethylcellulose, xanthan gum and the like, with preference given to carboxyvinyl polymers. Moreover, you may mix | blend 2 or more types of thickeners.

  The carboxyvinyl polymer of the present invention means a copolymer of acrylic acid, and for example, there are several types of 0.5% aqueous solution having different viscosities such as 4000 to 10000 mPa · s, 40000 to 60000 mPa · s, etc. However, in the present invention, it is preferable to mainly use a high viscosity type. The content of the thickener is preferably 0.1 to 3.0 w / w%, more preferably 0.3 to 1.0 w / w%, in the cream of the present invention. This range of content is because a cream having a good feeling in use and high stability can be obtained.

  As the surfactant in the present invention, nonionic surfactants are preferable, and in particular, polyoxyethylene sorbitan monooleate, polyethylene glycol monostearate, decaglyceryl monomyristate, sorbitan monostearate, polyoxyethylene cetyl ether, self Emulsified glyceryl monostearate is preferred. The content of the surfactant in the cream of the present invention is preferably 1.0 to 10 w / w%, more preferably 3.0 to 5.0 w / w%.

The cream of the present invention contains substantially no lower alcohol. The minoxidil-containing cream preparation of the present invention can dissolve minoxidil without substantially containing a lower alcohol, and is excellent in stability and feeling in use. The phrase "substantially free of lower alcohol" means that lower alcohol may not be blended, or it may be contained in an amount that can not dissolve Minoxidil contained in the cream preparation of the present invention. The amount of lower alcohol which can not dissolve Minoxidil, and the amount of lower alcohol which can ensure the stability of the cream, refer to 1. in the cream of the present invention. 0 or less mass%, particularly preferably 0 mass%. Lower alcohols include ethanol and isopropanol.

  It is preferable to further add a polyhydric alcohol to the cream of the present invention from the viewpoint of improving the feeling in use. As such a polyhydric alcohol, a 1, 3- butylene glycol, a dipropylene glycol, glycerol, propylene glycol etc. are mentioned, You may mix | blend 2 or more types. The content of the polyhydric alcohol is preferably 5 to 30 w / w%, more preferably 10 to 30 w / w%, in the cream preparation of the present invention from the viewpoint of feeling in use.

  Moreover, when the low surface tension component is blended in the cream of the present invention, the feeling of use is further improved. Examples of the low surface tension component include silicones such as dimethicone, dimethylsiloxane, and dimethylpolysiloxane, and two or more types may be blended. The content of the low surface tension component is preferably 0.1 w / w% to 10 w / w% in the cream of the present invention.

  The pH of the cream preparation of the present invention is preferably adjusted to 5-8. The pH regulator is not particularly limited, and acids and basic compounds which are formulated in ordinary pharmaceutical products and cosmetics can be used. For example, sodium hydroxide, diisopropanolamine, triethanolamine, hydrochloric acid, phosphoric acid, lactic acid and the like can be mentioned. In the case of pH control, these pH regulators can be used 1 type or in combination of 2 or more types.

  In addition, solid oil components such as stearyl alcohol and cetyl alcohol may be blended in the cream of the present invention. This is because when the solid oil component is contained, the properties of the cream become good.

  In the cream preparation of the present invention, in addition to the above-described components, various components which are usually used for external preparations can be blended as long as the effects of the present invention are not impaired. For example, hair-growing ingredients (6-benzylaminopurine, adenosine, pentadecanoic acid glycerides, birds of the order number, bamboo root ginseng etc.), vasodilators (carpronium chloride, benzyl nicotinate, extract of cerebrum, extract of ginseng extract, chili pepper etc), antihistamine (Diphenhydramine hydrochloride, isothipendyl hydrochloride, etc.) Anti-inflammatory agents (guaiazulene etc.), keratolytic agents (urea, salicylic acid etc.), bactericidal agents (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, piroctone olamine etc.) , Moisturizing agents (hyaluronic acid or salts thereof, chondroitin sulfate etc.), various animals and plants (yew, bovis, licorice, scutellaria root, sage, loquat, sage, sage, saffron, rosemary, sage, mokko, Extracts of moss, hops, placentas etc., vitamins (Retinol acetate, ascorbic acid, thiamine nitrate, pyridoxine hydrochloride, cyanocobalamin, tocopherol acetate, biotin etc.), antioxidants (dibutylhydroxytoluene, sodium pyrosulfite, tocopherol, Sodium edetate, ascorbic acid, isopropyl gallate, etc., oil (diisopropyl adipate, isopropyl myristate, various vegetable oils, various animal oils, hydrocarbons etc.), metabolic activators (panthenol etc.), adhesives, fragrances, refreshing Commonly used ingredients such as agents (l-menthol, peppermint oil, camphor etc.) and colorants can be blended.

  The cream preparation of the present invention is prepared by containing the above-mentioned components according to a conventional method.

  The cream preparation of the present invention thus obtained can be used as a skin preparation such as a hair preparation, an eyebrow preparation, an eyebrow preparation and the like.

  EXAMPLES Examples, comparative examples and test examples are described below, and the present invention is more specifically described, but the present invention is not limited by these examples and the like. The carboxyvinyl polymer used was Carbopol 980 manufactured by LUBRIZOL, and the isostearic acid used is isostearic acid EX manufactured by Higher Alcohol Industries.

Example 1
Minoxidil 1g
Isostearic acid 1.5 g
Carboxy vinyl polymer 1 g
Monooleic acid polyoxyethylene sorbitan 3g
(20E.O.)
15 g of glycerin
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
1 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, a mixture of 1.5 g of isostearic acid, 3 g of polyoxyethylene sorbitan monooleate (20E.O.), and 15 g of glycerin was heated to about 70 ° C., and 1 g of minoxidil was added thereto to stir to obtain an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.5.

(Example 2)
Minoxidil 1g
3 g of isostearic acid
Carboxy vinyl polymer 0.75 g
Polyethylene glycol monostearate 3g
(40E.O.)
10 g of 1,3-butylene glycol
0.3 g of dimethylpolysiloxane
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.75 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, a mixture of 3 g of isostearic acid, 3 g of polyethylene glycol monostearate (40 E.O.), 10 g of 1,3-butylene glycol and 0.3 g of dimethylpolysiloxane is heated to about 70 ° C, 1 g of minoxidil is added thereto and the mixture is stirred. It was a coconut oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature while stirring to obtain a preparation of pH 6.7.

(Example 3)
Minoxidil 1g
6 g of isostearic acid
0.3 g of carboxyvinyl polymer
Polyethylene glycol monostearate 3g
(40E.O.)
Polyoxyethylene Cured Castor Oil 40 1.5g
0.3 g of dimethylpolysiloxane
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.3 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, a mixture of 6 g of isostearic acid, 3 g of polyethylene glycol monostearate (40 E.O.), 40 1.5 g of polyoxyethylene hydrogenated castor oil, and 0.3 g of dimethylpolysiloxane is heated to about 70 ° C. The mixture was stirred to give an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.5.

(Example 4)
Minoxidil 1g
6 g of oleic acid
Carboxy vinyl polymer 0.5 g
5 g of decaglyceryl monomyristate
Diisopropanolamine Suitable amount Purified water 100g in total
0.5 g of carboxyvinyl polymer was dispersed in 60 g of purified water, and an aqueous solution heated to about 70 ° C. was used as an aqueous phase. Separately, a mixture of 6 g of oleic acid, 5 g of decaglyceryl monomyristate, and diisopropanolamine (appropriate amount) was heated to about 70 ° C., and 1 g of minoxidil was added thereto, and the mixture was stirred to obtain an oil phase. The oil phase was added to the aqueous phase, the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation having a pH of 5.8.

(Example 5)
Minoxidil 1g
10 g of isostearic acid
Carboxy vinyl polymer 0.5 g
Sorbitan monostearate 3g
Diisopropanolamine Suitable amount Purified water 100g in total
0.5 g of carboxyvinyl polymer was dispersed in 60 g of purified water, and an aqueous solution heated to about 70 ° C. was used as an aqueous phase. Separately, a mixture of 10 g of isostearic acid, 3 g of sorbitan monostearate and diisopropanolamine (appropriate amount) was heated to about 70 ° C., and 1 g of minoxidil was added thereto and stirred to obtain an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation having a pH of 5.1.

(Example 6)
Minoxidil 1g
10 g of isostearic acid
Carboxy vinyl polymer 0.5 g
Polyoxyethylene cetyl ether 3 g
(2E.O.)
Diisopropanolamine Suitable amount Purified water 100g in total
0.5 g of carboxyvinyl polymer was dispersed in 60 g of purified water, and an aqueous solution heated to about 70 ° C. was used as an aqueous phase. Separately, a mixture of 10 g of isostearic acid, 3 g of polyoxyethylene cetyl ether (2E.O.) and diisopropanolamine (appropriate amount) was heated to about 70 ° C., and 1 g of minoxidil was added thereto, and the mixture was stirred to obtain an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature while stirring to obtain a pH 5.0 formulation.

(Example 7)
Minoxidil 1g
10 g of isostearic acid
Carboxy vinyl polymer 0.5 g
Self-emulsifying glyceryl monostearate 3g
10 g of 1,3-butylene glycol
Diisopropanolamine Suitable amount Purified water 100g in total
0.5 g of carboxyvinyl polymer was dispersed in 60 g of purified water, and an aqueous solution heated to about 70 ° C. was used as an aqueous phase. Separately, a mixture of 10 g of isostearic acid, 3 g of self-emulsifiable glyceryl monostearate and diisopropanolamine (appropriate amount) was heated to about 70 ° C. 1 g of minoxidil was added thereto and stirred to obtain an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation having a pH of 5.2.

(Example 8)
Minoxidil 1g
10 g of isostearic acid
Carboxy vinyl polymer 0.5 g
Polyethylene glycol monostearate 3g
(40E.O.)
Dimethylpolysiloxane 0.5 g
Diisopropanolamine Suitable amount Purified water 100g in total
0.5 g of carboxyvinyl polymer was dispersed in 60 g of purified water, and an aqueous solution heated to about 70 ° C. was used as an aqueous phase. Separately, a mixture of 10 g of isostearic acid, 3 g of polyethylene glycol monostearate (40 E.O.), 0.5 g of dimethylpolysiloxane and diisopropanolamine (appropriate amount) is heated to about 70 ° C, to which 1 g of minoxidil is added and stirred. It was an oil phase. The oil phase was added to the aqueous phase, the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation having a pH of 5.8.

(Example 9)
Minoxidil 1g
3 g of isostearic acid
Carboxy vinyl polymer 0.75 g
Polyethylene glycol monostearate 3g
(40E.O.)
Dipropylene glycol 10g
0.3 g of dimethylpolysiloxane
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.75 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, a mixture of 3 g of isostearic acid, 3 g of polyethylene glycol monostearate (40 E.O.), 10 g of dipropylene glycol and 0.3 g of dimethylpolysiloxane is heated to about 70 ° C, 1 g of minoxidil is added thereto, and the mixture is stirred to obtain an oil phase. And The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature while stirring to obtain a preparation of pH 6.7.

(Example 10)
Minoxidil 1g
3 g of isostearic acid
Carboxy vinyl polymer 0.75 g
Polyethylene glycol monostearate 3g
(40E.O.)
10 g of glycerin
0.3 g of dimethylpolysiloxane
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.75 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, a mixture of 3 g of isostearic acid, 3 g of polyethylene glycol monostearate (40 E.O.), 10 g of glycerin and 0.3 g of dimethylpolysiloxane was heated to about 70 ° C, to which 1 g of minoxidil was added and stirred to obtain an oil phase. . The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.5.

(Example 11)
Minoxidil 1g
3 g of isostearic acid
Carboxy vinyl polymer 0.75 g
Polyethylene glycol monostearate 3g
(40E.O.)
Propylene glycol 10g
0.3 g of dimethylpolysiloxane
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.75 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, a mixture of 3 g of isostearic acid, 3 g of polyethylene glycol monostearate (40 E.O.), 10 g of propylene glycol and 0.3 g of dimethylpolysiloxane is heated to about 70 ° C, 1 g of minoxidil is added thereto, and the mixture is stirred to obtain an oil phase. did. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.5.

(Example 12)
Minoxidil 3g
6 g of isostearic acid
Carboxy vinyl polymer 0.8 g
Polyethylene glycol monostearate 3g
(40E.O.)
Polyoxyethylene Cured Castor Oil 40 1.5g
15 g of 1,3-butylene glycol
15 g of glycerin
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.8 g of carboxyvinyl polymer was dispersed in 50 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 6 g of isostearic acid, 3 g of polyethylene glycol monostearate (40 E.O.), 401.5 g of polyoxyethylene hydrogenated castor oil, 15 g of 1,3-butylene glycol, and 15 g of glycerin are heated to about 70 ° C. 3 g was added and stirred to obtain an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.5.

(Example 13)
Minoxidil 5g
30 g of isostearic acid
Carboxy vinyl polymer 1 g
Polyethylene glycol monostearate 3g
(40E.O.)
10 g of 1,3-butylene glycol
10 g of glycerin
0.3 g of dimethylpolysiloxane
Diisopropanolamine Suitable amount Purified water 100g in total
1 g of carboxyvinyl polymer was dispersed in 35 g of purified water, and an aqueous solution heated to about 70 ° C. was used as an aqueous phase. Separately, a mixture of 30 g of isostearic acid, 3 g of polyethylene glycol monostearate (40 E.O.), 10 g of 1,3-butylene glycol, 10 g of glycerin, 0.3 g of dimethylpolysiloxane, and diisopropanolamine (appropriate amount) is added to about 70 ° C. The mixture was warmed, 5 g of minoxidil was added thereto, and the mixture was stirred to give an oil phase. The oil phase was added to the aqueous phase, the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation having a pH of 5.9.

(Example 14)
Minoxidil 1g
6 g of isostearic acid
Stearyl alcohol 3g
Carboxy vinyl polymer 0.5 g
Polyethylene glycol monostearate 3g
(40E.O.)
10 g of 1,3-butylene glycol
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.5 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 6 g of isostearic acid, 3 g of stearyl alcohol, 3 g of polyethylene glycol monostearate (40 E.O.) and 10 g of 1,3-butylene glycol were heated to about 70 ° C, 1 g of minoxidil was added thereto, and the mixture was stirred to obtain an oil phase. . The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.4.

(Example 15)
Minoxidil 1g
6 g of isostearic acid
Stearyl alcohol 3g
Carboxy vinyl polymer 0.5 g
Polyethylene glycol monostearate 3g
(40E.O.)
10 g of 1,3-butylene glycol
0.3 g of dimethylpolysiloxane
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.5 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 6 g of isostearic acid, 3 g of stearyl alcohol, 3 g of polyethylene glycol monostearate (40 E.O.), 10 g of 1,3-butylene glycol and 0.3 g of dimethylpolysiloxane are heated to about 70 ° C, to which 1 g of minoxidil is added The mixture was further stirred to form an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.5.

(Example 16)
Minoxidil 0.2 g
0.3 g of isostearic acid
Carboxy vinyl polymer 0.5 g
Polyethylene glycol monostearate 3g
(40E.O.)
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.5 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 0.3 g of isostearic acid and 3 g of polyethylene glycol monostearate (40 E.O.) were heated to about 70 ° C., and 0.2 g of minoxidil was added thereto, followed by stirring to obtain an oil phase. The oil phase was added to the aqueous phase, the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a formulation of p7.0.

(Example 17)
Minoxidil 1g
6 g of isostearic acid
Carboxy vinyl polymer 1 g
Polyethylene glycol monostearate 3g
(40E.O.)
10 g of 1,3-butylene glycol
0.3 g of dimethylpolysiloxane
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
1 g of carboxyvinyl polymer was dispersed in 55 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 6 g of isostearic acid, 3 g of polyethylene glycol monostearate (40 E.O.), 10 g of 1,3-butylene glycol and 0.3 g of dimethylpolysiloxane are heated to about 70 ° C. It was a phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation having a pH of 7.8.

(Comparative example 1)
Minoxidil 1g
1 g of isostearic acid
Carboxy vinyl polymer 0.5 g
Polyethylene glycol monostearate 3g
(40E.O.)
Diisopropanolamine Suitable amount Purified water 100g in total
0.5 g of carboxyvinyl polymer was dispersed in 60 g of purified water, and an aqueous solution heated to about 70 ° C. was used as an aqueous phase. Separately, a mixture of 1 g of isostearic acid, 3 g of polyethylene glycol monostearate (40 E.O.) and diisopropanolamine (appropriate amount) was heated to about 70 ° C., 1 g of minoxidil was added thereto, and the mixture was stirred to obtain an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a pH 6.0 formulation.

(Comparative example 2)
Minoxidil 1g
10 g of tri (capryl / capric acid) glyceryl
Carboxy vinyl polymer 0.8 g
Monooleic acid polyoxyethylene sorbitan 3g
(20E.O.)
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.8 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 10 g of tri (capryl / capric acid) glyceryl and 3 g of polyoxyethylene sorbitan monooleate (20E.O.) were heated to about 70 ° C., 1 g of minoxidil was added thereto, and the mixture was stirred to obtain an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.5.

(Comparative example 3)
Minoxidil 1g
Liquid paraffin 10g
0.3 g of carboxyvinyl polymer
Monooleic acid polyoxyethylene sorbitan 3g
(20E.O.)
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.3 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 10 g of liquid paraffin and 3 g of polyoxyethylene sorbitan monooleate (20E.O.) were heated to about 70 ° C., and 1 g of minoxidil was added thereto to stir to form an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.5.

(Comparative example 4)
Minoxidil 1g
10 g of diisopropyl adipate
0.3 g of carboxyvinyl polymer
Monooleic acid polyoxyethylene sorbitan 3g
(20E.O.)
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.3 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 10 g of diisopropyl adipate and 3 g of polyoxyethylene sorbitan monooleate (20E.O.) were heated to about 70 ° C., and 1 g of minoxidil was added thereto, followed by stirring to obtain an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.5.

(Comparative example 5)
Minoxidil 1g
10 g of isopropyl myristate
Carboxy vinyl polymer 0.8 g
Monooleic acid polyoxyethylene sorbitan 3g
(20E.O.)
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.8 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 10 g of isopropyl myristate and 3 g of polyoxyethylene sorbitan monooleate (20E.O.) were heated to about 70 ° C., and 1 g of minoxidil was added to the mixture and stirred to obtain an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 6.4.

(Comparative example 6)
Minoxidil 1g
10 g of glyceryl tri-2-ethylhexanoate
Carboxy vinyl polymer 0.8 g
Monooleic acid polyoxyethylene sorbitan 3g
(20E.O.)
Sodium hydroxide aqueous solution Appropriate amount Purified water 100g in total
0.8 g of carboxyvinyl polymer was dispersed in 60 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 10 g of glyceryl tri-2-ethylhexanoate and 3 g of polyoxyethylene sorbitan monooleate (20E.O.) were heated to about 70 ° C, 1 g of minoxidil was added thereto, and the mixture was stirred to obtain an oil phase. The oil phase was added to the aqueous phase, and the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation having a pH of 6.1.

(Comparative example 7)
Minoxidil 1g
10 g of isostearic acid
0.3 g of carboxyvinyl polymer
Polyethylene glycol monostearate 3g
(40E.O.)
Sodium hydroxide aqueous solution appropriate amount ethanol 30g
100 g of purified water
0.3 g of carboxyvinyl polymer was dispersed in 45 g of purified water and heated to about 70 ° C. to obtain an aqueous solution. An aqueous solution of sodium hydroxide (appropriate amount) was added thereto to obtain an aqueous phase. Separately, 10 g of isostearic acid and 3 g of polyethylene glycol monostearate (40 E.O.) were heated to about 70 ° C., and 1 g of minoxidil was added thereto, and the mixture was stirred to obtain an oil phase. The oil phase was added to the aqueous phase, the remaining purified water was further added, and the mixture was stirred until uniform, and then cooled to room temperature while stirring. To this, 30 g of ethanol was added and stirred to obtain a preparation of pH 6.1.

(Comparative example 8)
Minoxidil 1g
10 g of isostearic acid
Polyethylene glycol monostearate 3g
(40E.O.)
100 g of purified water
10 g of isostearic acid and 3 g of polyethylene glycol monostearate (40 E.O.) were heated to about 70 ° C., and 1 g of minoxidil was added thereto and stirred to obtain an oil phase. This was added to 86 g of purified water, and stirred until uniform, and then cooled to room temperature with stirring to obtain a preparation of pH 5.4.

  The formulations of Examples 1 to 17 and Comparative Examples 1 to 8 are shown in Tables 1 and 2.

Test Example 1: Appearance of the preparation, feeling of use (roughness, moist feeling, white residue)
The appearance evaluation immediately after the preparation of Examples 1 to 17 and Comparative Examples 1 to 8 and the application to an appropriate amount of arms were carried out, and roughness, moist feeling and white residue were evaluated. The appearance is cream ○ ○, non cream ○ ×, without feeling of use ○ ○, something × ×, something that feels strongly ◎ 、, things that feel ○ ○, not feel ×: those with no white residue ◎, those without も の, and those with ×. The results are shown in Table 3.

  From the results in Table 3, it is found that the cream preparation (Examples 1 to 17) containing isostearic acid or oleic acid of the present invention at least 1.5 parts by mass of Minoxidil (Examples 1 to 17) has minoxidil dissolved and no feeling of using. Was good. On the other hand, a minoxidil-containing cream preparation (comparative examples 1 to 6) containing isostearic acid or oleic acid in an amount of less than 1.5 parts by mass of minoxidil or an oil other than minoxidil could not be dissolved when applied to the skin. Crystallized crystals produced a rough feeling, and the feeling of use was bad. In addition, the preparation containing ethanol (Comparative Example 7) did not become a cream in appearance.

Test Example 2 Stability of Preparation After preparation of Examples 1 to 17 and Comparative Example 8, the properties after two weeks at 65 ° C. were confirmed. A sample in which separation did not occur was rated ○, and a sample in which separation occurred was ×. The results are shown in Table 4.

  From the results of Table 4, the creams of Examples 1 to 17 were stable without separation of the preparation. On the other hand, the cream of Comparative Example 8 containing no carboxyvinyl polymer separated and was unstable.

  According to the present invention, it has become possible to provide a minoxidil-containing cream which is stable and excellent in feeling in use.

Claims (8)

Minoxidil, a lower fatty acid having a carbon number of 10 to 22 and / or a salt thereof having a carbon number of 10 to 22 relative to 1 part by weight of minoxidil, and a thickener and a surfactant, which is ethanol or isopropanol A cream whose content is at most 1.0% by mass, or does not contain the lower alcohol. Higher fatty acids are 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 The cream according to claim 1, which is selected from the group consisting of docosaexaenoic acid. The cream according to claim 1, wherein the higher fatty acid is isostearic acid and / or oleic acid. The cream according to any one of claims 1 to 3, wherein the thickener is a carboxyvinyl polymer. The cream according to any one of claims 1 to 4, wherein the surfactant is a nonionic surfactant. The cream according to any one of claims 1 to 5, further comprising a polyhydric alcohol. The cream according to claim 6, wherein the polyhydric alcohol is one or more selected from the group consisting of 1,3-butylene glycol, dipropylene glycol, glycerin and propylene glycol. The cream according to any one of claims 1 to 7, which has a pH of 5 to 8.