JP6221536B2 - 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 that is excellent in the stability and usability of the preparation.

Minoxidil has a chemical name of 6- (1-piperidinyl) -2,4-pyrimidinediamine-3-oxide and is known to be used as a hair growth agent (see Patent Document 1). Minoxidil is a drug that exhibits an excellent hair growth and hair growth effect when applied externally, and lotion-type minoxidil-containing external preparations are commercially available in Japan and overseas.
However, with a lotion type preparation, there is a concern that dripping may occur during use. Therefore, a minoxidil-containing external composition free from dripping is desired, but the actual situation is that a minoxidil-containing external composition with sufficiently suppressed dripping has not yet been provided.
On the other hand, since minoxidil has a property that it hardly dissolves in water and easily dissolves in alcohol, minoxidil-containing compositions for external use marketed domestically and abroad contain a large amount of alcohol. Therefore, there is a demand for a product that contains minoxidil that is less irritating and that can be used with peace of mind by people who are sensitive to alcohol.
A cream is considered as a preparation that can sufficiently suppress dripping, but there is no known low-irritant cream that contains minoxidil, has a stable preparation and good usability, and has a low alcohol concentration. .

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

Suzuki, Megumi et al., Hichikyokyo Journal, 51, 177-183 (2004) Sumi Sumi et al., Skin, 33 (11), 31-38 (1991)

  It is an object of the present invention to provide a minoxidil-containing external composition that can sufficiently dissolve minoxidil, is stable, has a good feeling of use, and has a low alcohol concentration and is low in irritation.

  As a result of intensive studies to solve the above problems, the present inventors have found that a cream containing minoxidil, a specific oil, a carboxyvinyl polymer and a partially saponified polyvinyl alcohol usually requires a large amount necessary for dissolving minoxidil. The present inventors have found that minoxidil can be sufficiently dissolved without containing any lower alcohol, and is stable and excellent in usability, thereby completing the present invention.

That is, the present invention
(1) A cream characterized by containing minoxidil, isostearic acid and / or oleic acid, carboxyvinyl polymer, partially saponified polyvinyl alcohol, and less than 10 w / w% lower alcohol,
(2) The cream according to (1), further comprising a polyhydric alcohol,
(3) The cream according to (2), wherein the polyhydric alcohol is one or more selected from the group consisting of 1,3-butylene glycol, dipropylene glycol, glycerin and propylene glycol,
(4) The cream according to any one of (1) to (3), wherein the pH is 4.5 to 9,
It is.

  INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a minoxidil-containing cream that can dissolve minoxidil, has low skin irritation, and is excellent in stability and use feeling.

  As the minoxidil used in the present invention, those having the quality usually used for pharmaceuticals can be appropriately used. The content of minoxidil is 1 to 10 w / w%, preferably 1 to 5 w / w% in the cream.

  Either or both of isostearic acid and / or oleic acid, which are oil components used in the present invention, may be used in combination. The content of isostearic acid and / or oleic acid is 1 to 30 w / w%, preferably 3 to 10 w / w% in the cream.

  The carboxyvinyl polymer in the present invention means a copolymer of acrylic acid. For example, there are several types having different viscosities such as viscosity of a 0.5% aqueous solution of 4000 to 10000 mPa · s and 40000 to 60000 mPa · s. However, in the present invention, it is preferable to mainly use a high viscosity type. The content of the carboxyvinyl polymer is preferably 0.1 to 3.0 w / w% in the cream, more preferably 0.1 to 2.0 w / w%, and most preferably 0.1 to 0.0. It is 8 w / w%. This is because the range of this content can provide an O / W emulsion-type cream with good usability and high stability.

  The partially saponified polyvinyl alcohol in the present invention means a partially saponified polyvinyl acetate obtained by polymerizing vinyl acetate. For example, the viscosity of a 4% aqueous solution is 4.8 to 5.8 mPa · s, There are several types with different viscosities such as 20.5 to 24.5 mPa · s, 27.0 to 33.0 mPa · s, and 40.0 to 46.0 mPa · s. Regardless, if a saponification degree generally used is 70 to 96 mol%, a stable O / W emulsion type cream can be produced. From the viewpoints of formulation and usability, partially saponified polyvinyl alcohol having a saponification degree of 78 to 96 mol% is preferable, and partially saponified polyvinyl alcohol having a saponification degree of 85 to 90 mol% is particularly preferable. The content of the partially saponified polyvinyl alcohol is preferably 0.1 to 4.0 w / w%, more preferably 0.1 to 3.0 w / w%, most preferably 0 with respect to the total amount of the composition. 0.1 to 1.2 w / w%.

  The lower alcohol in the present invention is ethanol, isopropanol or the like, preferably ethanol. The content of the lower alcohol in the cream is less than 10 w / w%. The blending of 10 w / w% or more is not preferable because not only the irritation to the skin but also the stability of the cream of the present invention is significantly deteriorated.

  The cream of the present invention preferably further contains a polyhydric alcohol from the viewpoint of improving the feeling of use. Examples of such a polyhydric alcohol include 1,3-butylene glycol, dipropylene glycol, glycerin, propylene glycol, and the like, and two or more kinds may be blended. The content of the polyhydric alcohol is preferably 5 to 30 w / w%, more preferably 10 to 15 w / w% in the cream from the point of use feeling.

  The pH of the cream of the present invention is preferably adjusted to 4.5-9. The pH regulator is not particularly limited, but an acid or basic compound blended in a normal pharmaceutical or cosmetic can be used. For example, sodium hydroxide, diisopropanolamine, hydrochloric acid, phosphoric acid, lactic acid and the like can be mentioned. In adjusting the pH, these pH adjusting agents can be used alone or in combination of two or more.

  The cream of the present invention can produce a stable cream without adding a surfactant that is usually required when preparing the cream. However, you may mix | blend surfactant as needed. In the cream of the present invention, in addition to the above-described components, various components that are usually used in external preparations can be blended within a range that does not impair the effects of the present invention. For example, excipients, hair-growth ingredients (6-benzylaminopurine, adenosine, pentadecanoic acid glyceride, garlic, bamboo ginseng, etc.), vasodilators (carpronium chloride, benzyl nicotinate, assembly extract, ginseng extract, chili pepper tincture) Etc.), antihistamines (diphenhydramine hydrochloride, isothipentyl hydrochloride, etc.), anti-inflammatory agents (guaiazulene, etc.), keratolytic agents (urea, salicylic acid, etc.), bactericides (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salt, piroctone) Olamine, etc.), moisturizers (hyaluronic acid or salts thereof, chondroitin sulfate, etc.), various animals and plants (yew, buttonpi, licorice, hypericum, appendix, loquat, sagebrush, comfrey, ashitaba, saffron, sanshishi, rosemary, sage, Mo Extracts of Kou, Seimo, Hop, Placenta, etc., Vitamins (Retinol acetate, Ascorbic acid, Thiamine nitrate, Cyanocobalamin, Biotin, etc.), Antioxidants (Dibutylhydroxytoluene, Sodium pyrosulfite, Tocopherol, Sodium edetate, Ascorbine Acid, isopropyl gallate, etc.), solubilizers (diisopropyl adipate, isopropyl myristate, various vegetable oils, various animal oils, hydrocarbons, etc.), metabolic activators (pantenol, etc.), adhesives, fragrances, cooling agents (mint) Oil, camphor, etc.) and commonly used ingredients such as dyes can be blended.

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

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

  EXAMPLES Examples, comparative examples, and test examples will be described below, and the present invention will be described more specifically. However, the present invention is not limited by these examples. In addition, Carbopol 980 manufactured by LUBRIZOL was used as the carboxyvinyl polymer, and Gohsenol EG-05 (saponification degree: 86.5-89.0 mol%) manufactured by Nippon Synthetic Chemical Industry was used as the partially saponified polyvinyl alcohol.

Example 1
Minoxidil 1g
Isostearic acid 3g
Carboxy vinyl polymer 0.75g
1g partially saponified polyvinyl alcohol
1,3-butylene glycol 15g
Sodium hydroxide aqueous solution 100g of purified water
0.75 g of carboxyvinyl polymer was dispersed in 50 g of purified water and heated to about 50 ° C. to obtain an aqueous solution. Further, 1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, a mixture of 3 g of isostearic acid and 15 g of 1,3-butylene glycol was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 7.0.

(Example 2)
Minoxidil 1g
6g of isostearic acid
Carboxy vinyl polymer 0.5g
1g partially saponified polyvinyl alcohol
Diisopropanolamine appropriate amount purified water 100g
Carboxyvinyl polymer 0.5g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. The two aqueous solutions were combined into an aqueous phase. Separately, a mixture of 6 g of isostearic acid and diisopropanolamine was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 having a pH of 5.2.

(Example 3)
Minoxidil 2g
10g of isostearic acid
Carboxy vinyl polymer 0.8g
Partially saponified polyvinyl alcohol 1.2g
1,3-butylene glycol 10g
Diisopropanolamine appropriate amount purified water 100g
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1.2 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. The two aqueous solutions were combined into an aqueous phase. Separately, a mixture of 10 g of isostearic acid, 10 g of 1,3-butylene glycol and diisopropanolamine was heated to about 70 ° C., and 2 g of minoxidil was dissolved therein 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 it became homogeneous, and then cooled to room temperature with stirring to obtain a formulation having a pH of 5.4.

Example 4
Minoxidil 1g
10g of isostearic acid
Carboxy vinyl polymer 0.8g
Partially saponified polyvinyl alcohol 1.2g
5g polyoxyethylene sorbitan monooleate
(20 EO)
Diisopropanolamine appropriate amount purified water 100g
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1.2 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. The two aqueous solutions were combined into an aqueous phase. Separately, a mixture of 10 g of isostearic acid, 5 g of polyoxyethylene sorbitan monooleate (20E.O.), and diisopropanolamine was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 it was homogeneous, and then cooled to room temperature with stirring to obtain a preparation having a pH of 4.9.

(Example 5)
Minoxidil 1g
10g of isostearic acid
Carboxy vinyl polymer 0.8g
1g partially saponified polyvinyl alcohol
Polyethylene glycol monostearate 5g
(40E.O.)
Diisopropanolamine appropriate amount purified water 100g
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. The two aqueous solutions were combined into an aqueous phase. Separately, a mixture of 10 g of isostearic acid, 5 g of polyethylene glycol monostearate (40E.O.), and diisopropanolamine was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 it was uniform, and then cooled to room temperature with stirring to obtain a formulation having a pH of 6.1.

(Example 6)
Minoxidil 1g
10g of isostearic acid
Carboxy vinyl polymer 0.8g
1g partially saponified polyvinyl alcohol
5 g polyoxyethylene sorbitan monostearate
5g sorbitan monostearate
Diisopropanolamine appropriate amount purified water 100g
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. The two aqueous solutions were combined into an aqueous phase. Separately, a mixture of 10 g of isostearic acid, 5 g of polyoxyethylene sorbitan monostearate, 5 g of sorbitan monostearate, and diisopropanolamine was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 pH 6.0 formulation.

(Example 7)
Minoxidil 1g
6g of isostearic acid
Carboxy vinyl polymer 0.5g
1g partially saponified polyvinyl alcohol
1,3-butylene glycol 10g
Diisopropanolamine appropriate amount purified water 100g
Carboxyvinyl polymer 0.5g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. The two aqueous solutions were combined into an aqueous phase. Separately, a mixture of 6 g of isostearic acid, 10 g of 1,3-butylene glycol and diisopropanolamine was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 it became homogeneous, and then cooled to room temperature with stirring to obtain a preparation having a pH of 5.6.

(Example 8)
Minoxidil 1g
6g of isostearic acid
Carboxy vinyl polymer 0.5g
1g partially saponified polyvinyl alcohol
Dipropylene glycol 10g
Diisopropanolamine appropriate amount purified water 100g
Carboxyvinyl polymer 0.5g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. The two aqueous solutions were combined into an aqueous phase. Separately, a mixture of 6 g of isostearic acid, 10 g of dipropylene glycol and diisopropanolamine was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 it was uniform, and then cooled to room temperature with stirring to obtain a formulation having a pH of 5.5.

Example 9
Minoxidil 1g
6g of isostearic acid
Carboxy vinyl polymer 0.5g
1g partially saponified polyvinyl alcohol
Glycerin 10g
Diisopropanolamine appropriate amount purified water 100g
Carboxyvinyl polymer 0.5g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. The two aqueous solutions were combined into an aqueous phase. Separately, a mixture of 6 g of isostearic acid, 10 g of glycerin and diisopropanolamine was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 it was uniform, and then cooled to room temperature with stirring to obtain a formulation having a pH of 5.5.

(Example 10)
Minoxidil 1g
6g of isostearic acid
Carboxy vinyl polymer 0.5g
1g partially saponified polyvinyl alcohol
10g of propylene glycol
Diisopropanolamine appropriate amount purified water 100g
Carboxyvinyl polymer 0.5g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. The two aqueous solutions were combined into an aqueous phase. Separately, a mixture of 6 g of isostearic acid, 10 g of propylene glycol and diisopropanolamine was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 it became homogeneous, and then cooled to room temperature with stirring to obtain a preparation with pH 5.6.

(Example 11)
Minoxidil 1g
10g of isostearic acid
Carboxy vinyl polymer 0.8g
Partially saponified polyvinyl alcohol 1.2g
Sodium hydroxide aqueous solution 100g of purified water
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1.2 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of isostearic acid was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 pH 6.4 preparation.

Example 12
Minoxidil 1g
Oleic acid 10g
Carboxy vinyl polymer 0.8g
Partially saponified polyvinyl alcohol 1.2g
Sodium hydroxide aqueous solution 100g of purified water
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1.2 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. The two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of oleic acid was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 pH 6.4 preparation.

(Example 13)
Minoxidil 1g
10g of isostearic acid
Carboxyvinyl polymer 0.1g
0.1g of partially saponified polyvinyl alcohol
Sodium hydroxide aqueous solution appropriate amount ethanol 5g
100g of purified water
0.1 g of carboxyvinyl polymer was dispersed in 50 g of purified water and heated to about 50 ° C. to obtain an aqueous solution. Further, 0.1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of isostearic acid was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 was added 5 g of ethanol and stirred to obtain a preparation having a pH of 6.0.
(Example 14)
Minoxidil 1g
6g of isostearic acid
Carboxy vinyl polymer 0.75g
1g partially saponified polyvinyl alcohol
1,3-butylene glycol 10g
Sodium hydroxide aqueous solution 100g of purified water
0.75 g of carboxyvinyl polymer was dispersed in 50 g of purified water and heated to about 50 ° C. to obtain an aqueous solution. Further, 1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, a mixture of 6 g of isostearic acid and 10 g of 1,3-butylene glycol was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 having a pH of 8.7.

(Comparative Example 1)
Minoxidil 1g
Tri (capryl / capric acid) glyceryl 10g
Carboxy vinyl polymer 0.8g
Partially saponified polyvinyl alcohol 1.2g
Sodium hydroxide aqueous solution 100g of purified water
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1.2 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of tri (capryl / capric acid) glyceryl was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 obtain a preparation with pH 6.3.

(Comparative Example 2)
Minoxidil 1g
Liquid paraffin 10g
Carboxy vinyl polymer 0.8g
Partially saponified polyvinyl alcohol 1.2g
Sodium hydroxide aqueous solution 100g of purified water
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1.2 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of liquid paraffin was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 pH 6.5 formulation.

(Comparative Example 3)
Minoxidil 1g
Diisopropyl adipate 10g
Carboxy vinyl polymer 0.8g
Partially saponified polyvinyl alcohol 1.2g
Sodium hydroxide aqueous solution 100g of purified water
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1.2 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of diisopropyl adipate was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 pH 6.5 formulation.

(Comparative Example 4)
Minoxidil 1g
10g isopropyl myristate
Carboxy vinyl polymer 0.8g
Partially saponified polyvinyl alcohol 1.2g
Sodium hydroxide aqueous solution 100g of purified water
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1.2 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of isopropyl myristate was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 pH 6.4 preparation.

(Comparative Example 5)
Minoxidil 1g
10g glyceryl tri-2-ethylhexanoate
Carboxy vinyl polymer 0.8g
Partially saponified polyvinyl alcohol 1.2g
Sodium hydroxide aqueous solution 100g of purified water
Carboxyvinyl polymer 0.8g was disperse | distributed to purified water 50g, and it heated to about 50 degreeC, and obtained aqueous solution. Further, 1.2 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of glyceryl tri-2-ethylhexanoate was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 pH 6.5 formulation.

(Comparative Example 6)
Minoxidil 1g
10g of isostearic acid
Carboxyvinyl polymer 0.1g
0.1g of partially saponified polyvinyl alcohol
Sodium hydroxide aqueous solution 10g ethanol 10g
100g of purified water
0.1 g of carboxyvinyl polymer was dispersed in 50 g of purified water and heated to about 50 ° C. to obtain an aqueous solution. Further, 0.1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of isostearic acid was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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, 10 g of ethanol was added and stirred to obtain a preparation with pH 6.2.

(Comparative Example 7)
Minoxidil 1g
10g of isostearic acid
Carboxyvinyl polymer 0.1g
0.1g of partially saponified polyvinyl alcohol
Sodium hydroxide aqueous solution 15g ethanol
100g of purified water
0.1 g of carboxyvinyl polymer was dispersed in 50 g of purified water and heated to about 50 ° C. to obtain an aqueous solution. Further, 0.1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of isostearic acid was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 was added 15 g of ethanol and stirred to obtain a preparation with pH 6.3.

(Comparative Example 8)
Minoxidil 1g
10g of isostearic acid
Carboxyvinyl polymer 0.1g
0.1g of partially saponified polyvinyl alcohol
Sodium hydroxide aqueous solution 20g ethanol
100g of purified water
0.1 g of carboxyvinyl polymer was dispersed in 50 g of purified water and heated to about 50 ° C. to obtain an aqueous solution. Further, 0.1 g of partially saponified polyvinyl alcohol was dissolved in 10 g of purified water heated to about 50 ° C. to obtain an aqueous solution. Two aqueous solutions were combined, and an aqueous sodium hydroxide solution (appropriate amount) was added to form an aqueous phase. Separately, 10 g of isostearic acid was heated to about 70 ° C., and 1 g of minoxidil was dissolved therein 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 was added 20 g of ethanol and stirred to obtain a preparation with pH 6.5.

Test Example 1 Usability of the preparations Examples 1 to 14 and Comparative Examples 1 to 5 were applied in appropriate amounts to the arms, and the roughness and moist feeling were evaluated. A rough texture was rated as ◯, a certain texture as x, a moist feeling as ◎, a feeling as ○, and a feeling as x. The results are shown in Tables 1-3.

  From the results of Tables 1 to 3, the cream preparation containing the isostearic acid or oleic acid of the present invention was good in use feeling. On the other hand, the minoxidil-containing creams containing oils other than isostearic acid or oleic acid (Comparative Examples 1 to 5) were rough when applied to the skin, and the usability was poor. This is because minoxidil cannot be sufficiently dissolved in the preparation and is in a dispersed state.

Test Example 2 Preparation Stability Properties of Examples 1 to 14 and Comparative Examples 6 to 8 were confirmed after 2 weeks passed at 65 ° C. The case where separation did not occur was marked with ◯, and the case where separation occurred was marked with ×. The results are shown in Tables 4-6.

表４〜６の結果から、エタノールの含有量が少ない実施例１〜１３のクリーム剤は製剤が分離せず、安定であった。一方、エタノールを１０ｗ／ｗ％以上含有する比較例６〜８のクリーム剤は分離した。

From the results of Tables 4 to 6, the creams of Examples 1 to 13 having a small content of ethanol were stable because the preparations were not separated. On the other hand, the creams of Comparative Examples 6 to 8 containing 10 w / w% or more of ethanol were separated.

According to the present invention, it is possible to provide a minoxidil-containing cream that is stable and excellent in usability.

Claims (4)

(A) minoxidil, (b) isostearic acid and / or oleic acid, (c) carboxyvinyl polymer, (d) partially saponified polyvinyl alcohol having a saponification degree of 70 to 96 mol% , and (e) lower than less than 10 w / w% A cream containing an alcohol or not containing a lower alcohol , wherein the lower alcohol is ethanol or isopropanol .   Furthermore, a polyhydric alcohol is contained, The cream agent of Claim 1 characterized by the above-mentioned. The cream according to claim 2, 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 3, which has a pH of 4.5 to 9.