Composition for external use

Abstract

To provide a minoxidil-containing composition for external use which suppresses discoloration of a preparation with time in a minoxidil-containing composition for external use obtained by blending at least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or a salt thereof, a pantothenyl ethyl ether, panthenol, hinokitiol and diphenhydramine and / or a salt thereof.SOLUTION: There is provided a composition for external use which suppresses discoloration of a preparation with time by using a specific polyhydric alcohol, that is, there is provided a composition for external use which comprises: at least one active ingredient selected from the group consisting of minoxidil, glycyrrhetinic acid and / or a salt thereof, a pantothenyl ethyl ether, panthenol, hinokitiol and diphenhydramine and / or a salt thereof; propylene glycol; and an acid.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an external composition containing minoxidil as an active ingredient. More specifically, it relates to a technique for suppressing the coloring over time of a minoxidil-containing external composition blended with at least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or its salt, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or its salt.

Background Art

[0002] Minoxidil is called 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide in chemical name and is known to be applicable as a hair growth agent (Patent Document 1), and there are many reports as a drug that exhibits an excellent hair growth and hair follicle activation effect. In addition, it has been reported that glycyrrhetinic acid has an anti-inflammatory effect (Patent Document 2), pantothenyl ethyl ether has a cell-activating effect (Patent Document 3), panthenol has a wound healing promoting effect (Patent Document 4), hinokitiol has an antibacterial effect (Patent Document 5), and diphenhydramine has an itching suppressing effect (Patent Document 6), and they are used in many hair growth agents.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Summary of the Invention

Problems to be Solved by the Invention

[0004] In order to develop an excellent hair growth agent, the inventors of the present invention produced a minoxidil-containing external composition containing minoxidil and an acid and formulated with a specific active ingredient, namely glycyrrhetinic acid, pantothenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine hydrochloride, and evaluated its stability. Unexpectedly, it was found that the addition of the specific active ingredient worsened the coloring compared to a minoxidil-alone preparation. The present invention aims to provide a minoxidil-containing external composition in which the coloring of the preparation is suppressed, the minoxidil-containing external composition being formulated with at least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine, and / or its salts.

[0005] There have been no reported examples regarding whether or not an interaction that affects the worsening of the coloring of the preparation occurs between 2 w / w% or more of minoxidil and glycyrrhetinic acid and / or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine and / or its salts.

Means for Solving the Problems

[0006] As a result of intensive studies to solve the above problems, the inventors of the present invention have found that when producing a minoxidil-containing external composition formulated with glycyrrhetinic acid and / or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine and / or its salts, a minoxidil-containing external composition in which the coloring of the preparation over time is suppressed can be produced by selecting a specific polyhydric alcohol, and thus the present invention has been completed.

[0007] That is, the present invention provides (1) a) 2 w / w% or more of minoxidil, b) At least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or its salts, c) Propylene glycol, and d) An external composition characterized by containing an acid, (2) The external composition according to (1), wherein the concentration of minoxidil is 5 w / w% or more, (3) a) 2 w / w% or more of minoxidil, b) At least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or its salts, c) Propylene glycol, and d) A step of mixing to prepare a mixture, A method for producing an external composition, comprising the step of adding e) water and f) a lower alcohol to the mixture to prepare the total amount, It is as follows.

Effect of the Invention

[0008] According to the present invention, in an external composition containing 2 w / w% or more of minoxidil blended with at least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or its salts, it has become possible to provide an external composition containing minoxidil that suppresses the coloring of the preparation over time.

Mode for Carrying Out the Invention

[0009] According to the present invention, an external composition containing 2 w / w% or more of minoxidil, at least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or its salts, propylene glycol, and an acid suppresses the coloring of the minoxidil preparation.

[0010] In the topical composition of the present invention, minoxidil of a quality usually used in pharmaceuticals can be appropriately used. Further, according to the present invention, the content of minoxidil is 2 w / w% or more, more preferably 3 w / w% or more, and even more preferably 5 w / w% or more. When it is 5 w / w% or more, the coloring of the preparation further progresses, and thus in the present invention, the significance of carrying out within this range is great.

[0011] The polyhydric alcohol used in the topical composition of the present invention is propylene glycol from the viewpoint of suppressing the coloring of the preparation over time, which is an effect of the present invention. The blending amount of propylene glycol is preferably 2 to 55 w / w% in the total composition, more preferably 2 to 35 w / w%, and even more preferably 2 to 15 w / w%. In the topical composition of the present invention, polyhydric alcohols other than propylene glycol may be included within a range that does not impair the effects of the present invention, but it is preferable from the viewpoint of the effects of the present invention not to blend glycerin, polyethylene glycol, and dipropylene glycol, and it is most preferable from the viewpoint of the effects of the present invention to blend only propylene glycol.

[0012] In order to dissolve minoxidil in the base, it is known to use an acid. As the acid used in the topical composition of the present invention, components that adjust the liquidity of the topical composition of the present invention to 7 or less are preferable, and examples include inorganic acids or organic acids having 6 or less carbon atoms. Specifically, they are phosphoric acid, citric acid, lactic acid, hydrochloric acid, acetic acid, sulfuric acid, nitric acid, tartaric acid, maleic acid, malic acid, and gluconic acid, and preferably phosphoric acid, citric acid, lactic acid, and tartaric acid. These acids may be combined singly or in combination of two or more.

[0013] Further, the topical composition of the present invention is preferably adjusted to a pH in the range of 4.0 to 9.5, 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 to the skin during use, the drug permeability, and the usability. Further, as the upper limit of the pH, it is preferably less than 6.5, more preferably 6.3 or less, and even more preferably 6.1 or less.

[0014] In the topical composition of the present invention, the compounding amount of glycyrrhetinic acid and / or its salt used is preferably 0.01 to 1 w / w% in the topical composition, more preferably 0.02 to 0.5 w / w%, still more preferably 0.05 to 0.1 w / w% from the viewpoint of the problem of suppressing coloring of the present invention, and further, preferably 0.02 parts by mass or more with respect to 1 part by mass of minoxidil. The compounding amount of pantothenyl ethyl ether is preferably 0.1 to 5 w / w% in the topical composition, more preferably 0.2 to 2 w / w%, still more preferably 0.2 to 1 w / w% from the viewpoint of the problem of suppressing coloring of the present invention, and further, preferably 0.2 parts by mass or more with respect to 1 part by mass of minoxidil. The compounding amount of panthenol is preferably 0.1 to 5 w / w% in the topical composition, more preferably 0.2 to 2 w / w%, still more preferably 0.2 to 1 w / w% from the viewpoint of the problem of suppressing coloring of the present invention, and further, preferably 0.2 parts by mass or more with respect to 1 part by mass of minoxidil. The compounding amount of hinokitiol is preferably 0.01 to 0.1 w / w% in the topical composition, more preferably 0.01 to 0.05 w / w%, still more preferably 0.02 to 0.05 w / w% from the viewpoint of the problem of suppressing coloring of the present invention, and further, preferably 0.01 parts by mass or more with respect to 1 part by mass of minoxidil. The compounding amount of diphenhydramine and / or its salt is preferably 0.01 to 1 w / w% in the topical composition, more preferably 0.02 to 0.5 w / w%, still more preferably 0.05 to 0.1 w / w% from the viewpoint of the problem of suppressing coloring of the present invention, and further, preferably 0.02 parts by mass or more with respect to 1 part by mass of minoxidil.

[0015] In the external composition of the present invention, higher alcohols can be further blended if necessary. 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 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 being more preferred. 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 even more preferred. 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 10 w / w% in the external composition, more preferably 0.1 to 5 w / w%, and even more preferably 0.25 to 1.5 w / w%.

[0016] In the external composition of the present invention, lower alcohols and water can be further blended if necessary. As the lower alcohol, those having 1 to 5 carbon atoms are preferred, and 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, even 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%.

[0017] In the topical composition of the present invention, a higher fatty acid can be further blended if necessary. As examples of the higher fatty acid, those having 10 to 22 carbon atoms are preferable. For example, 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. can be mentioned, and one or a combination of two or more of these may be used. Among these, those having 18 carbon atoms are preferable, and isostearic acid or oleic acid is particularly preferable. The blending amount of the higher fatty acid is preferably 0.1 to 10 w / w% in the total composition, and more preferably 1 to 6 w / w%.

[0018] In the topical composition of the present invention, a surfactant can be further blended if necessary. However, the addition of the surfactant may affect the feeling of use and the skin absorption of minoxidil. In the topical composition of the present invention, since the solubility of minoxidil can be ensured without blending the surfactant, it is preferably substantially free of the surfactant.

[0019] In the external composition of the present invention, various active ingredients and auxiliary components used in general external preparations can be blended as long as the effects of the present invention are not impaired. For example, excipients, hair growth components (6-benzylaminopurine, adenosine, glyceryl pentadecanoate, polygonum multiflorum, etc.), vasodilators (calpronium chloride, benzyl nicotinate, assemblage extract, angelica acutiloba extract, glycyrrhiza glabra 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.), moisturizers (hyaluronic acid or its salts, chondroitin sulfate, etc.), extracts of various animals and plants (taxus cuspidata, button mushroom, licorice, viola arvensis, aconite, loquat, mugwort, comfrey, ashitaba, saffron, ginseng, rosemary, sage, mokko, seimokko, hop, 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 ether, 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 blended.

[0020] Examples of the dosage forms of the external composition of the present invention include solutions, lotions, and the like. The external composition of the present invention is prepared by containing the above components according to a conventional method.

[0021] The thus obtained external composition of the present invention can be used as skin application preparations such as hair preparations, eyelash preparations, eyebrow preparations, and the like.

[0022] Examples of the method for producing the external composition of the present invention include, for example, a method of preparing a mixture by mixing a) minoxidil at 2 w / w% or more, b) glycyrrhetinic acid and / or its salt, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or its salt, at least one active ingredient selected from the group consisting of, c) propylene glycol, and d) an acid, and adding e) water and f) a lower alcohol to the mixture to prepare the total amount; a method of preparing a mixture by mixing a) minoxidil at 2 w / w% or more, b) glycyrrhetinic acid and / or its salt, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or its salt, at least one active ingredient selected from the group consisting of, c) propylene glycol, d) an acid, e) water, and adding f) a lower alcohol to the mixture to prepare the total amount, and the like.

[0023] Examples, comparative examples, and reference examples are described below to more specifically explain the present invention, but the present invention is not limited by these examples or the like.

Examples

[0024] (Examples 1 to 10, Comparative Examples 1 to 17, and Reference Example 1) The formulations of Examples 1 to 10, Comparative Examples 1 to 17, and Reference Example 1 are shown in Tables 1 to 2. Each component described in Tables 1 to 2 was mixed, stirred, and dissolved, and ethanol was added to make the total amount 100 g to prepare the preparation.

[0025]

Table 1

[0026]

Table 2

[0027] (Test Method 1: Thermal Stability Test - 1) After storing the test solutions of Example 1, Comparative Examples 1 to 3, and Reference Example 1 at 65 °C (at the prevailing relative humidity) for 3 days, the preparation was visually observed to confirm the color tone.

[0028]

Table 3

[0029] (Result) As is clear from Table 3, the coloring of the minoxidil-containing preparation (Example 1) in which propylene glycol was blended in the polyhydric alcohol did not progress over time (colorless), but the coloring of the minoxidil-containing preparations (Comparative Examples 1 to 3) in which polyhydric alcohol other than propylene glycol was blended progressed over time (slightly yellow).

[0030] (Test Method 2: Thermal Stability Test - 2) After storing the test solutions of Example 2 and Comparative Examples 4 to 5 at 65 °C (relative humidity as it goes) for 5 days, the preparations were visually observed and the color tone was confirmed.

[0031]

Table 4

[0032] (Result) As is clear from Table 4, the coloring of the minoxidil-containing preparation (Example 2) in which propylene glycol was blended in the polyhydric alcohol did not progress over time (colorless), but the coloring of the minoxidil-containing preparations (Comparative Examples 4 to 5) in which polyhydric alcohol other than propylene glycol was blended progressed over time (slightly yellow).

[0033] Also, even with the same slightly yellow color, the preparation with a higher concentration of glycyrrhetinic acid showed a stronger color tone.

[0034] (Test Method 3: Thermal Stability Test - 3) After storing the test solutions of Examples 3 to 10, Comparative Examples 6 to 17 and Reference Example 1 at 65 °C (relative humidity as it goes) for 5 days, the preparations were visually observed and the color tone was confirmed.

[0035]

Table 5

[0036] (Result) As is clear from Table 5, the coloring of the minoxidil-containing preparations (Examples 3 to 10) containing propylene glycol in the polyhydric alcohol did not progress over time (colorless), but the coloring of the minoxidil-containing preparations (Comparative Examples 6 to 17) containing a polyhydric alcohol other than propylene glycol progressed over time (slightly yellow or yellow).

Industrial Applicability

[0037] According to the present invention, it has become possible to provide a minoxidil-containing external composition in which the coloring of the preparation over time is suppressed, the minoxidil-containing external composition containing at least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or its salt, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or its salt.

Claims

1. a) 2% or more w / w of minoxidil; b) 0.1 to 5 w / w% panthenol c) propylene glycol, and d) 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, maleic acid, malic acid, and gluconic acid; and b) a panthenol content of 0.1 parts by mass or more per 1 part by mass of minoxidil.

2. 3. The lotion or liquid preparation according to claim 2, wherein the concentration of minoxidil is 5 w / w % or more.

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