JP5353168B2 - Minoxidil-containing external preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a minoxidil-containing liquid for external use, which exhibits restrained dripping and simultaneously an enhanced sense of use. <P>SOLUTION: The liquid for external use contains minoxidil, hyaluronic acid or its salt, 1,3-butylene glycol, ethanol, and water. <P>COPYRIGHT: (C)2009,JPO&amp;INPIT

Description

  The present invention relates to an external solution containing minoxidil as an active ingredient, and can be applied to the fields of pharmaceuticals and quasi drugs.

  Minoxidil has a chemical name of 6- (1-piperidinyl) -2,4-pyrimidinediamine-3-oxide and is known to be used as a hair restorer (see Patent Document 1). In order to provide a minoxidil-containing external preparation, since minoxidil does not dissolve in water, a solvent having a property of dissolving minoxidil, such as an alcohol, is essential. However, when a minoxidil-containing external preparation is applied to the head, there is a concern about dripping into the eyes due to dripping and accompanying alcohol irritation to the eyes. As a method for preventing such dripping, a thickener is tried, but stickiness is felt strongly, and there are problems in use feeling such as slow drying.

  Here, it is known that hyaluronic acid has an excellent water retention ability and forms a viscous gel even in a dilute solution (see Non-Patent Document 1). Moreover, in order to exhibit the effect as a humectant, the formulation which mix | blended comparatively high concentration hyaluronic acid is known (refer patent document 2).

  However, while hyaluronic acid is added, its viscosity increases due to its ability to form a gel, but there are problems similar to those of a thickening agent such as stickiness.

U.S. Pat. No. 4,139,619 JP-A-7-48230 Okuyama et al., 1982, Fragrance Journal, No. 56, 39-42

  The object of the present invention is to provide a liquid preparation for external use which does not spill without accompanying the disadvantages of the thickening agent, and to provide a liquid preparation containing minoxidil which has a little stickiness and good usability.

  As a result of diligent research to solve the above-mentioned problems, the inventors have found that it is difficult to dripping by blending hyaluronic acid or a salt thereof and a specific polyhydric alcohol into a minoxidil-containing ethanol water-containing liquid. The present invention was completed by finding that a minoxidil-containing external preparation containing an excellent feeling of use was obtained.

That is, the present invention
(1) A liquid preparation for external use comprising minoxidil, hyaluronic acid or a salt thereof, 1,3-butylene glycol, ethanol and water,
(2) External liquid preparation according to (1), wherein the content of hyaluronic acid or a salt thereof is 0.005 to 0.02 w / v%,
(3) The external solution according to (1) or (2), wherein the content of 1,3-butylene glycol is 5 to 30 w / v%,
(4) External liquid agent as described in any one of (1)-(3) whose content of water is 5-30 w / v%,
(5) External liquid formulation as described in any one of (1)-(4) whose content of ethanol is 25-70 w / v%,
(6) The external preparation according to any one of (1) to (5), wherein the pH is 5.5 to 9.5,
(7) A method for preventing dripping by blending hyaluronic acid or a salt thereof and 1,3-butylene glycol in an external liquid preparation containing minoxidil, ethanol and water.

  INDUSTRIAL APPLICABILITY According to the present invention, it was possible to provide a minoxidil-containing external preparation that does not sag and retains a good feeling of use.

  The present invention is described in detail below.

  When hyaluronic acid or its salt and 1,3-butylene glycol are blended in order to suppress dripping of an aqueous solution containing ethanol containing minoxidil, a decrease in feeling of use such as stickiness accompanying an increase in stickiness occurs. In addition, a minoxidil-containing external preparation that hardly drips liquid could be obtained.

  In the present invention, the blending (content) amount of minoxidil is not particularly limited, but is preferably 1 w / v% or more, and more preferably 1 to 10 w / v%, from which a hair growth effect can be sufficiently expected. As the minoxidil to be used, those having the quality usually used for pharmaceuticals can be appropriately used.

  Examples of the salt of hyaluronic acid include a sodium salt. The blending (content) amount of hyaluronic acid or a salt thereof is preferably 0.005 to 0.02 w / v% in the liquid. The molecular weight of hyaluronic acid is not particularly limited, but is preferably 500,000 to 2,000,000 in terms of ease of handling. Moreover, the hyaluronic acid or its salt to be used can be used as appropriate in quality usually used for pharmaceuticals.

  The blending (containment) amount of ethanol is preferably 25 to 70 w / v% in the liquid agent, and the blending (containment) amount of water is preferably 5 to 30 w / v% in the liquid agent, and the blending of 1,3-butylene glycol ( The content is preferably 5 to 30 w / v% in the liquid, and more preferably 5 to 20 w / v% in the liquid. As ethanol, water and 1,3-butylene glycol to be used, those of quality used for pharmaceuticals can be appropriately used.

  The pH of the solution of the present invention is preferably in the range of 5.5 to 9.5, and more preferably in the range of 6 to 8 which is neutral. For adjusting the pH of the solution, an appropriate acid and / or base can be used as the pH adjuster. Examples of the pH adjuster include citric acid, hydrochloric acid, lactic acid, phosphoric acid, tartaric acid, and gluconic acid. These can be used, and those of the quality used for pharmaceuticals can be used as appropriate.

  Furthermore, as a component which can be mix | blended with this invention liquid, the component (henceforth a "selective component") chosen from the group which consists of menthol, vitamin E acetate, and pantotenyl ethyl ether is mentioned, There is no restriction in particular, and it can be determined taking into consideration the feeling of use and the stability of minoxidil. For example, menthol is 0.2 to 0.4 w / v% in the liquid, and vitamin E acetate is 0.01 to 0 in the liquid. .15 w / v%, pantotenyl ethyl ether can be blended so as to be 0.5 to 1.5 w / v% in the liquid. As the selection components to be used, those of the quality used for pharmaceuticals can be used as appropriate.

  In the liquid preparation of the present invention, in addition to the above-described components, various components, excipients, and hair-growth components used in general external preparations (6-benzylaminopurine, adenosine, pentadecanoic acid glyceride, garlic, bamboo ginseng Etc.), vasodilators (carpronium chloride, benzyl nicotinate, assembly extract, ginseng extract, red pepper tincture, etc.), antihistamines (diphenhydramine hydrochloride, isotipezil hydrochloride, etc.), anti-inflammatory agents (guaiazulene, etc.), keratolytic agents (urea, Salicylic acid, etc.), bactericides (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, piroctone olamine, etc.), moisturizers (chondroitin sulfate, etc.), various animals and plants (yew, buttonpi, licorice, hypericum, appendix, loquat , Kawaramugi, Comfrey, Ashitaba Extracts from saffron, sanshishi, rosemary, sage, mokko, seimokko, hop, placenta, etc., vitamins (retinol acetate, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, etc.), antioxidants (dibutylhydroxytoluene, pyro Sodium sulfite, tocopherol, sodium edetate, ascorbic acid, isopropyl gallate, etc.), solubilizers (diisopropyl adipate, isopropyl myristate, various vegetable oils, various animal oils, hydrocarbons, etc.), metabolic activators (pantenol, etc.), Commonly used components such as a polymer (carboxyvinyl polymer, etc.), an adhesive, a fragrance, a refreshing agent (mint oil, camphor, etc.), and a dye can be blended within a range that does not impair the effects of the present invention. However, since the addition of a surfactant affects the skin absorption of minoxidil, it is preferable that the liquid preparation of the present invention does not substantially contain a surfactant.

  The liquid preparation of the present invention is prepared by blending each of the above components according to a conventional method. For example, after mixing and dissolving each component including minoxidil, hyaluronic acid or its salt, 1,3-butylene glycol and ethanol, adjust the pH, adjust the volume by adding purified water, and filter as necessary. By carrying out the above, the desired minoxidil-containing external preparation can be obtained.

  The liquid preparation of the present invention thus obtained can be used as an appropriate external liquid preparation such as a lotion preparation, an aerosol preparation or a tonic preparation, more specifically as a hair preparation, a skin application preparation or the like.

  The present invention will be described more specifically with reference to the following examples. However, the present invention is not limited by these examples. Sodium hyaluronate having a molecular weight of 500,000 to 2,000,000 was used.

Example 1
1 g of minoxidil, 0.3 g of L-menthol, 0.08 g of vitamin E acetate, 1 g of pantotenyl ethyl ether, 0.017 g of sodium hyaluronate, 10 g of 1,3-butylene glycol, and 60 g of ethanol are mixed, stirred and dissolved. Then, an appropriate amount of citric acid was added to adjust the pH to 8, and then purified water was added to make 100 mL to obtain a solution.

Example 2
Mix 1 g of minoxidil, 0.3 g of L-menthol, 0.08 g of vitamin E acetate, 1 g of pantotenyl ethyl ether, 0.005 g of sodium hyaluronate, 10 g of 1,3-butylene glycol, and 60 g of ethanol, dissolve and dissolve. Then, an appropriate amount of citric acid was added to adjust the pH to 8, and then purified water was added to make 100 mL to obtain a solution.

Comparative Example 1
Mix 1 g of minoxidil, 0.3 g of L-menthol, 0.08 g of vitamin E acetate, 1 g of pantotenyl ethyl ether, 10 g of 1,3-butylene glycol and 60 g of ethanol, dissolve them in a stirring frame, and add an appropriate amount of citric acid. After adjusting the pH to 8, purified water was added to 100 mL to obtain a liquid.
Comparative Example 2
1 g of minoxidil, 10 g of propylene glycol, and 60 g of ethanol were mixed, stirred and dissolved, and then purified water was added to make 100 mL to obtain a liquid.
Comparative Example 3
1 g of minoxidil, 0.3 g of L-menthol, 0.08 g of vitamin E acetate, 1 g of pantotenyl ethyl ether, 0.002 g of sodium hyaluronate, 10 g of 1,3-butylene glycol, and 60 g of ethanol are mixed, stirred and dissolved. Then, an appropriate amount of citric acid was added to adjust the pH to 8, and then purified water was added to make 100 mL to obtain a solution.
Comparative Example 4
1 g of minoxidil, 0.3 g of L-menthol, 0.08 g of vitamin E acetate, 1 g of pantotenyl ethyl ether, 0.06 g of sodium hyaluronate, 10 g of 1,3-butylene glycol, and 60 g of ethanol are mixed, stirred and dissolved. Then, an appropriate amount of citric acid was added to adjust the pH to 8, and then purified water was added to make 100 mL to obtain a solution.
Comparative Example 5
Mix 1 g of minoxidil, 0.3 g of L-menthol, 0.08 g of vitamin E acetate, 1 g of pantotenyl ethyl ether, 0.017 g of sodium hyaluronate, 10 g of glycerin and 60 g of ethanol After adding and adjusting pH to 8, purified water was added to make 100 mL, and the liquid agent was obtained.

Test example 1
Using the liquid agents of Examples 1 and 2 and Comparative Examples 1 to 5, thermal paper was placed on a flat plate at an angle of 40 °. 20 μL of each sample was discharged at an angle of 90 ° with respect to the ground, and after 30 seconds, the dripping distance on the thermal paper was measured. The results are shown in FIG.

Test example 2
The feeling of use of the liquid preparations of Example 1 and Comparative Example 2 was evaluated by a sensory test by six subjects. As an evaluation method, a method based on a left-right pair comparison using a half head was used. That is, 1 mL of the solution of Example 1 was applied to the left side of the subject's head and 1 mL of the solution of Comparative Example 2 was applied to the left side, and the stickiness was evaluated. The test was conducted so that the subject could not identify the contents of the liquid. The evaluation criteria are as follows. A score of “I don't know” means that I don't know if there is stickiness.
Score 5: Don't know Score 4: No score 3: Somewhat score 2: Some score 1: Very good Furthermore, in the evaluation of stickiness, the panelists who gave the result of score 1 to score 3 were apt to feel stickiness of the liquid It was also evaluated whether or not. The results of the sensory test are shown in Table 1.

Test example 3
The feeling of use of the liquid agents of Comparative Examples 2 to 5 was evaluated by a sensory test by four test subjects. As an evaluation method, 100 μL of the solution of Comparative Examples 3 to 5 was applied to one arm of the subject and 100 μL of the solution of Comparative Example 2 was applied to the other arm, and the stickiness was evaluated. The test was conducted so that the subject could not identify the contents of the liquid. The results of the sensory test are shown in Table 2.

From Test Examples 1 and 2, the liquid agent of Example 1 was blended with hyaluronic acid and 1,3-butylene glycol. The dripping distance was effectively suppressed as compared with the comparative example.
From Test Examples 1 to 3, when 1,3-butylene glycol is blended as a solvent, when the blending (content) amount of hyaluronic acid is 0.06 w / v% or more, the feeling of use such as stickiness decreases. Therefore, the hyaluronic acid concentration has an optimum range, and it was considered that the effect of the present invention contributed to the blending balance of the whole preparation. On the other hand, in the prescription in which glycerin or propylene glycol, which are the same polyhydric alcohols, was used instead of 1,3-butylene glycol, dripping was effectively suppressed and the feeling of use could not be kept good. .

  According to the present invention, since dripping of the minoxidil-containing liquid agent can be effectively suppressed and the feeling of use can be kept good, an easy-to-handle minoxidil-containing hair preparation and the like can be provided.

It is a graph which shows the dripping distance of Example 1 and 2 and the sample of Comparative Examples 1-5.

Claims (6)

A liquid preparation for external use comprising minoxidil, 0.005 to 0.02 w / v% hyaluronic acid or a salt thereof, 1,3-butylene glycol, ethanol and water. The liquid for external use according to claim 1, wherein the content of 1,3-butylene glycol is 5 to 30 w / v%. The liquid for external use according to claim 1 or 2, wherein the water content is 5 to 30 w / v%. The external solution according to any one of claims 1 to 3, wherein the content of ethanol is 25 to 70 w / v%. The external solution according to any one of claims 1 to 4, wherein the pH is 5.5 to 9.5. A method for preventing dripping by blending 0.005-0.02 w / v% hyaluronic acid or a salt thereof and 1,3-butylene glycol in an external liquid preparation containing minoxidil, ethanol and water.

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