Composition for external use

Abstract

To provide a minoxidil-containing composition for external use which improves the precipitation caused by minoxidil which may occur after application in the minoxidil-containing composition for external use.SOLUTION: It is found out that blending of menthol can improve the precipitation caused by minoxidil which may occur after application in a minoxidil-containing composition for external use. That is, there is provided a composition for external use which comprises 2 w / w% or more of minoxidil, menthol, a specific acid and / or its salt and propylene glycol.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an external composition containing minoxidil. More specifically, it relates to a technique for suppressing precipitation derived from minoxidil that may occur upon application of the minoxidil-containing external composition.

Background Art

[0002] Minoxidil is called 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide by its chemical name 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-stimulating effect. Since minoxidil-containing external compositions are used daily on the head for a long period of time, compositions that are excellent in terms of the feeling of use are also required. When using a composition with a higher concentration of minoxidil, precipitation derived from minoxidil may rarely occur after application and may look like dandruff. Therefore, in an external composition containing minoxidil, a composition that suppresses precipitation derived from minoxidil that may occur after application is desired. On the other hand, menthol is used in many preparations as a cooling agent.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] An object of the present invention is to provide a minoxidil-containing external composition that suppresses precipitation derived from minoxidil that may occur after application for the minoxidil-containing external composition.

Means for Solving the Problems

[0005] As a result of intensive studies to solve the above problems, the present inventors have found that a composition containing minoxidil, a specific acid and / or its salt, a specific polyhydric alcohol, and menthol can suppress precipitation derived from minoxidil, and have thus completed the present invention.

[0006] That is, the present invention provides: (1) An externally applicable composition containing minoxidil, characterized by containing (a) 2 w / w% or more of minoxidil, (b) menthol, (c) at least one acid selected from the group consisting of phosphoric acid, citric acid, lactic acid, hydrochloric acid, acetic acid, sulfuric acid, nitric acid, tartaric acid, gluconic acid, and maleic acid and / or a salt thereof, and (d) propylene glycol. (2) The externally applicable composition according to (1), wherein the concentration of minoxidil is 5 w / w% or more. It is as follows.

Advantages of the Invention

[0007] According to the present invention, it has become possible to provide an externally applicable composition containing minoxidil that suppresses precipitation derived from minoxidil that may occur after application of the externally applicable composition containing minoxidil. Furthermore, unexpectedly, it can be provided as a clear externally applicable composition containing minoxidil in which no precipitate is formed in the preparation.

Modes for Carrying Out the Invention

[0008] According to the present invention, an externally applicable composition containing minoxidil, menthol, a specific acid and / or its salt, and a specific polyhydric alcohol suppresses precipitation derived from minoxidil that may occur after application, and no precipitate is formed in the preparation.

[0009] In the topical composition of the present invention, minoxidil that is of a quality normally used in pharmaceuticals can be appropriately used. Further, according to the present invention, as the content of minoxidil increases, the problem of precipitation that may occur after applying the preparation becomes more significant. Therefore, the higher the concentration of minoxidil in the topical composition, the greater the significance of implementing the present invention. Specifically, 2 w / w% or more in the topical composition of the present invention is preferable, 3 w / w% or more is more preferable, and most preferably 5 w / w% or more.

[0010] The specific acid and / or its salt in the topical composition of the present invention is phosphoric acid, citric acid, lactic acid, hydrochloric acid, acetic acid, sulfuric acid, nitric acid, tartaric acid, gluconic acid, maleic acid, or a salt thereof, from the viewpoint of the effect of the present invention of obtaining a clear preparation without precipitation. Further, among these, phosphoric acid, citric acid, lactic acid, and tartaric acid are preferable, and phosphoric acid and lactic acid are most preferable. These acids and / or their salts are components that adjust the liquidity of the topical composition of the present invention to 7 or less, and all of them are inorganic acids or their salts or organic acids having 6 or less carbon atoms or their salts. The specific acid and / or its salt of the present invention may be used alone or in combination of two or more.

[0011] Further, the polyhydric alcohol used in the topical composition of the present invention is propylene glycol. The blending amount of propylene glycol is preferably 2 to 55 w / w% in the total composition, and more preferably 5 to 35 w / w%. In the topical composition of the present invention, polyhydric alcohols other than propylene glycol may be included as long as the effects of the present invention are not impaired, but it is preferable from the viewpoint of the effects of the present invention not to blend glycerin and polyethylene glycol, and it is most preferable from the viewpoint of the effects of the present invention to blend only propylene glycol.

[0012] Further, the topical composition of the present invention is preferably adjusted to have a pH in the range of 4.0 to 9.5, and more preferably in the range of 5.0 to 7.0, from the viewpoints of the stability of the main drug component minoxidil, the irritation feeling on the skin during use, the drug permeability, the usability, etc. Further, as the upper limit of the pH, it is preferably less than 6.5, more preferably 6.3 or less, and still more preferably 6.1 or less.

[0013] In the external composition of the present invention, the content of menthol used is preferably 0.05 to 2 w / w% in the external composition, more preferably 0.1 to 1.5 w / w% from the viewpoint of the effect of the present invention.

[0014] Higher alcohols can be further blended into the external composition of the present invention as needed. Examples of higher alcohols include diacetone alcohol, caproyl alcohol, caprylyl alcohol, capryl alcohol, lauryl alcohol, tridecanol, myristyl alcohol, pentadecanol, cetyl alcohol, hexyl decanol, isocetyl alcohol, cetostearyl alcohol, heptadecanol, stearyl alcohol, oleyl alcohol, isostearyl alcohol, octyl decanol, nonadecanol, arachyl alcohol, octyldodecanol, heneicosanol, behenyl alcohol, and decyltetradecanol with 6 to 24 carbon atoms. Among them, diacetone alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, hexyl decanol, cetostearyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, arachyl alcohol, octyldodecanol, behenyl alcohol, and decyltetradecanol are more preferable. Among these, diacetone alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, hexyl decanol, cetostearyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, arachyl alcohol, octyldodecanol, behenyl alcohol, and decyltetradecanol are even more preferable. The higher alcohols of the present invention may be used alone or in combination of two or more. The content of the higher alcohol is preferably 0.05 to 2 w / w% in the external composition, more preferably 0.1 to 1.5 w / w%, and even more preferably 0.25 to 1.5 w / w% from the viewpoint of the effect of the present invention.

[0015] In the topical composition of the present invention, lower alcohols and water can be further blended as needed. As 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 is preferably 20 w / w% or more in the total composition, more preferably 30 w / w% or more, more preferably 35 w / w% or more, and still more preferably 50 w / w% or more. The blending amount of water is preferably 2 to 75 w / w%, more preferably 5 to 50 w / w%.

[0016] In the topical composition of the present invention, higher fatty acids can be further blended as needed. Examples of the higher fatty acid preferably have 10 to 22 carbon atoms, such as 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, docosahexaenoic acid, etc., and one or more of these may be combined. Among these, those having 18 carbon atoms are preferred, and particularly isostearic acid or oleic acid is preferred. The blending amount of the higher fatty acid is preferably 0.1 to 10 w / w% in the total composition, more preferably 1 to 6 w / w%.

[0017] In the topical composition of the present invention, surfactants can be further blended as needed. However, the addition of surfactants may affect the feeling of use and the skin absorption of minoxidil. In the lotion of the present invention, since a sufficient precipitation improvement effect can be obtained even without blending surfactants, it is preferably substantially free of surfactants.

[0018] In the external composition of the present invention, in addition to the above-described components, necessary active ingredients and auxiliary components can be added as long as the effects of the present invention are not impaired. As medicinal ingredients preferably added to and formulated in the lotion of the present invention, components selected from the group consisting of vitamin E acetate, pantothenyl ethyl ether, hinokitiol, pyridoxine hydrochloride, glycyrrhetinic acid, diphenhydramine hydrochloride, and panthenol can be mentioned. The addition amounts of these selected components are not particularly restricted and can be experimentally determined while considering the feel of use, the stability of minoxidil, the solvent-based composition, and the like.

[0019] In the external composition of the present invention, in addition to the above-described components, various active ingredients and auxiliary components used in general external preparations can be formulated as long as the effects of the present invention are not impaired. For example, excipients, hair growth components (6-benzylaminopurine, adenosine, glyceryl pentadecanoate, fleeceflower root, etc.), vasodilators (calpronium chloride, benzyl nicotinate, assembly extract, wild ginseng extract, chikusetsu ginseng tincture, capsicum tincture, etc.), antihistamines (isothipendyl hydrochloride, etc.), anti-inflammatory agents (guaiazulene, etc.), keratolytic agents (urea, salicylic acid, etc.), bactericides (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, piroctone olamine, etc.), humectants (hyaluronic acid or its salts, chondroitin sulfate, etc.), extracts of various animals and plants (Japanese yew, button mushroom, licorice, chickweed, aconite, loquat, mugwort, comfrey, ashitaba, saffron, ginseng, rosemary, sage, mokko, seimokko, hops, placenta, saw palmetto, pumpkin seed, etc.), vitamins (retinol acetate, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, etc.), antioxidants (dibutylhydroxytoluene, sodium pyrosulfite, tocopherol, sodium edetate, ascorbic acid, isopropyl gallate, etc.), solubilizing agents (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.), dyes, and other commonly used components can be formulated.

[0020] The external composition of the present invention can be made into an appropriate external composition such as a lotion, an aerosol, a tonic, a cream, an ointment, a gel, etc. Among these, the most preferable dosage form is a lotion.

[0021] The preparation of the external composition of the present invention is prepared by containing the above-mentioned respective components according to a conventional method. The external composition of the present invention thus obtained can be used as a skin application preparation such as a hair preparation, an eyelash preparation, an eyebrow preparation, etc.

[0022] Examples, comparative examples and test examples are described below to explain the present invention more specifically, but the present invention is not limited by these examples etc.

Examples

[0023] (Reference Example 1) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of phosphoric acid, and the total amount was made 100 g with ethanol, and stirred for about 1 hour to obtain an external composition having a pH of 6.1.

[0024] (Reference Example 2) 2 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of phosphoric acid, and the total amount was made 100 g with ethanol, and stirred for about 1 hour to obtain an external composition having a pH of 5.8.

[0025] (Reference Example 3) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of citric acid, and the total amount was made 100 g with ethanol, and stirred for about 1 hour to obtain an external composition having a pH of 6.1.

[0026] (Reference Example 4) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of lactic acid, and the total amount was made 100 g with ethanol, and stirred for about 1 hour to obtain an external composition having a pH of 6.0.

[0027] (Reference Example 5) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of tartaric acid, and the total amount was adjusted to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.0.

[0028] (Example 1) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of phosphoric acid, 0.3 g of menthol, and the total amount was adjusted to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.1.

[0029] (Example 2) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of citric acid, 0.3 g of menthol, and the total amount was adjusted to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.1.

[0030] (Example 3) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of lactic acid, 0.3 g of menthol, and the total amount was adjusted to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.0.

[0031] (Example 4) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of hydrochloric acid, 0.3 g of menthol, and the total amount was adjusted to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.0.

[0032] (Example 5) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of acetic acid, 0.3 g of menthol, and the total amount was adjusted to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.1.

[0033] (Example 6) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of sulfuric acid, 0.3 g of menthol, and the total amount was adjusted to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.0.

[0034] (Example 7) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of nitric acid, 0.3 g of menthol, and the total amount was made up to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.0.

[0035] (Example 8) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of tartaric acid, 0.3 g of menthol, and the total amount was made up to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.0.

[0036] (Example 9) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of gluconic acid, 0.3 g of menthol, and the total amount was made up to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.0.

[0037] (Example 10) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of maleic acid, 0.3 g of menthol, and the total amount was made up to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.0.

[0038] (Example 11) 2 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of phosphoric acid, 0.3 g of menthol, and the total amount was made up to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 5.8.

[0039] (Comparative Example 1) 5 g of minoxidil, 15 g of polyethylene glycol 400, 20 g of purified water, an appropriate amount of phosphoric acid, 0.3 g of menthol, and the total amount was made up to 100 g with ethanol, and stirred for about 1 hour to obtain an external composition with a pH of 6.3.

[0040] (Comparative Example 2) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of dl-malic acid, 0.3 g of menthol, and the total amount was made up to 100 g with ethanol, and stirred for about 1 hour to prepare an external composition with a pH of 6.0.

[0041] (Comparative Example 3) 5 g of minoxidil, 15 g of propylene glycol, 20 g of purified water, an appropriate amount of boric acid, 0.3 g of menthol, and the total amount was adjusted to 100 g with ethanol, and stirred for about 1 hour to prepare an external composition with a pH of 6.0.

[0042] (Comparative Example 4) 2 g of minoxidil, 15 g of polyethylene glycol 400, 20 g of purified water, an appropriate amount of phosphoric acid, 0.3 g of menthol, and the total amount was adjusted to 100 g with ethanol, and stirred for about 1 hour to prepare an external composition with a pH of 5.9.

[0043] (Test Example 1: Precipitation Test - 1) Regarding Reference Example 1, Example 1, and Comparative Example 1, 100 μL of the external composition was dropped onto a glass petri dish, and after 24 hours, the crystal precipitation derived from minoxidil was visually evaluated. The results are shown in Table 1. Those with improved precipitation compared to Reference Example 1 were marked as ○, and those without improved precipitation were marked as ×. The test was conducted 3 times.

[0044]

Table 1

[0045] In Reference Example 1 containing propylene glycol, crystal precipitation derived from minoxidil was confirmed, but in Example 1 containing menthol, it was improved. On the other hand, in Comparative Example 1 containing polyethylene glycol as a polyhydric alcohol, the precipitation was not improved.

[0046] (Test Example 2: Precipitation Test - 2) Regarding Reference Example 2, Example 11, Comparative Example 4, Example 2, Reference Example 3, Example 3, Reference Example 4, Example 8, and Reference Example 5, 100 μL of the external composition was dropped onto a glass plate, and after 24 hours, the crystal precipitation derived from minoxidil was visually evaluated. The results are shown in Table 2. Those with an excellent precipitation improvement effect compared to the reference example were marked as ◎, those with a recognized precipitation improvement effect were marked as ○, and those without a recognized precipitation improvement effect were marked as ×. The test was conducted 3 times.

[0047]

Table 2

[0048] In Reference Examples 2 to 5 containing propylene glycol, crystallization precipitation derived from minoxidil was confirmed, but Examples 2, 3, 8, and 11 containing menthol were improved. On the other hand, in Comparative Example 4 containing polyethylene glycol as a polyhydric alcohol, the precipitation was not improved.

[0049] <Test Example 3: Preparation Test of Lotion>[ Regarding the lotions of Examples 1 to 10 and Comparative Examples 2 to 3, a preparation test of the preparation was carried out. Immediately after the preparation, the lotion in the beaker was visually confirmed, and those that obtained a clear preparation without precipitate were marked as ○, and those that had precipitate in the lotion were marked as ×. The results are shown in Table 3.

[0050]

Table 3

[0051] As is clear from Table 3, in Examples 1 to 10 using the acid of the present invention, all the compounding components were dissolved, and a clear lotion without precipitate was obtained. On the other hand, when malic acid or boric acid was used, precipitate occurred in the lotion (Comparative Examples 2 and 3).

Industrial Applicability

[0052] According to the present invention, it has become possible to provide an excellent minoxidil-containing external composition that suppresses precipitation derived from minoxidil that may occur after application and suppresses the formation of precipitate in the external composition in a minoxidil-containing external composition.

Claims

【Claim 1】 The invention described in this specification.

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