External components

Abstract

The objective is to provide a minoxidil-containing topical composition containing tocopherol and / or its derivatives that suppresses discoloration of the formulation over time. [Solution] We have found that by using a specific polyhydric alcohol, it is possible to suppress the discoloration of the formulation over time in a minoxidil-containing topical composition that contains tocopherol and / or its derivatives. Specifically, the topical composition is characterized by containing minoxidil, tocopherol and / or its derivatives, propylene glycol, a lower alcohol of 30 w / w% or more, and an acid.

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 of a minoxidil-containing external composition containing tocopherol and / or its derivative over time.

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 on it as a drug that exhibits an excellent hair growth and hair follicle activation effect. In addition, it is known that tocopherol acetate, which is one of the tocopherol derivatives, has an antioxidant effect (Patent Document 2) and a hair growth effect (Patent Document 3), and it is used in many hair growth agents.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0004] In order to develop an excellent hair growth agent, the present inventors manufactured a minoxidil-containing external composition in which tocopherol and / or its derivative was blended in a composition containing minoxidil and an acid, and evaluated its stability. Unexpectedly, it was found that the coloring of the preparation progressed. An object of the present invention is to provide a minoxidil-containing external composition in which the coloring of the preparation is suppressed in a minoxidil-containing external composition containing tocopherol and / or its derivative. [Means for solving the problem]

[0005] As a result of diligent research to solve the above problems, the present inventors have discovered that when manufacturing a minoxidil-containing topical composition containing tocopherol and / or its derivatives, a minoxidil-containing topical composition that suppresses discoloration of the formulation over time can be manufactured by selecting a specific polyhydric alcohol, and have thus completed the present invention.

[0006] In other words, the present invention is (1) a) Minoxidil at 2 w / w% or higher, b) Tocopherol and / or derivatives thereof, c) Propylene glycol d) Lower alcohols of 30 w / w% or higher, e) A topical composition characterized by containing an acid, (2) The topical composition described in (1), wherein the concentration of minoxidil is 5 w / w% or more. (3) a) Minoxidil at 2 w / w% or higher, b) Tocopherol and / or derivatives thereof, c) Propylene glycol and A method for producing an external composition, comprising the steps of e) preparing by mixing acids and f) adding water and d) a lower alcohol to the mixture to prepare the total volume, That is the case. [Effects of the Invention]

[0007] The present invention makes it possible to provide a minoxidil-containing topical composition containing 2 w / w% or more minoxidil, which suppresses discoloration of the formulation over time. [Modes for carrying out the invention]

[0008] According to the present invention, a topical composition containing 2 w / w% or more of minoxidil, tocopherol and / or its derivatives, propylene glycol, 30 w / w% or more of a lower alcohol and an acid suppresses the discoloration of minoxidil preparations. The minoxidil used in the topical composition of the present invention can be of a quality commonly used in pharmaceuticals. Furthermore, according to the present invention, the minoxidil content is 2 w / w% or more, more preferably 3 w / w% or more, and even more preferably 5 w / w% or more. At 5 w / w% or more, the coloring of the formulation progresses further, so there is great significance in carrying out the present invention within this range.

[0009] The polyhydric alcohol used in the topical composition of the present invention is propylene glycol, in terms of its effect of suppressing the discoloration of the formulation over time. The amount of propylene glycol in the total composition is preferably 2 to 55 w / w%, more preferably 5 to 35 w / w%, and even more preferably 5 to 15 w / w%. The topical composition of the present invention may contain other polyhydric alcohols other than propylene glycol, as long as they do not impair the effects of the present invention. However, it is preferable not to include glycerin or polyethylene glycol from the viewpoint of the effects of the present invention, and it is most preferable to include only propylene glycol from the viewpoint of the effects of the present invention.

[0010] It is known that an acid is used to dissolve minoxidil in a base. The acid used in the topical composition of the present invention is preferably a component that adjusts the pH of the topical composition of the present invention to 7 or less, and examples include inorganic acids or organic acids with 6 or fewer carbon atoms. Specifically, these include 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 used individually or in combination of two or more.

[0011] Furthermore, the pH of the topical composition of the present invention is preferably adjusted to a range of 4.0 to 9.5, and more preferably to a range of 5.0 to 7.0, from the viewpoint of the stability of the main ingredient minoxidil, the sensation of irritation to the skin during use, the penetration of the drug, and the feel of use. Moreover, the upper limit of the pH is preferably less than 6.5, more preferably 6.3 or less, and even more preferably 6.1 or less.

[0012] In the topical composition of the present invention, the amount of tocopherol and / or its derivative used is preferably 0.01 to 1 w / w%, more preferably 0.02 to 0.5 w / w%, even more preferably 0.05 to 0.1 w / w%, and preferably 0.01 parts by mass or more per 1 part by mass of minoxidil, in order to address the issue of suppressing discoloration.

[0013] The topical composition of the present invention may further contain higher alcohols as needed. Examples of higher alcohols include diacetone alcohol, caproyl alcohol, caprylyl alcohol, caprylic alcohol, lauryl alcohol, tridecanol, myristyl alcohol, pentadecanol, cetyl alcohol, hexyldecanol, isocetyl alcohol, cetostearyl alcohol, heptadecanol, stearyl alcohol, oleyl alcohol, isostearyl alcohol, octyldecanol, nonadecanol, arachidodecanol, octyldodecanol, henicosanol, behenyl alcohol, and decyltetradecanol, which are more preferably of which diacetone alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, hexyldecanol, cetostearyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, arachidodecanol, octyldodecanol, behenyl alcohol, and decyltetradecanol. The higher alcohols of the present invention may be used individually or in combination of two or more. The content of higher alcohols in the topical composition is preferably 0.05 to 10 w / w%, more preferably 0.1 to 5 w / w%, and even more preferably 0.25 to 1.5 w / w%.

[0014] The topical composition of the present invention may further contain lower alcohols and water as needed. Preferred lower alcohols have 1 to 5 carbon atoms, such as ethanol and isopropanol, and these may be used in combination. The lower alcohol content must be 30 w / w% or more of the total composition. Preferably, it is 35 w / w% or more, more preferably 40 w / w% or more, and even more preferably 50 w / w% or more. The amount of water is preferably 2 to 75 w / w%, more preferably 5 to 50 w / w%.

[0015] The topical composition of the present invention may further contain higher fatty acids as needed. Examples of higher fatty acids include those with 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, and docosahexaenoic acid, which may be used individually or in combination of two or more. Of these, those with 18 carbon atoms are preferred, and isostearic acid or oleic acid are particularly preferred. The amount of higher fatty acid included is preferably 0.1 to 10 w / w%, and more preferably 1 to 6 w / w%, in the total composition.

[0016] The topical composition of the present invention may further contain surfactants as needed. However, the addition of surfactants may affect the feel of use and the skin absorption of minoxidil, and since the solubility of minoxidil can be ensured without the inclusion of surfactants in the topical composition of the present invention, it is preferable that the composition be substantially surfactant-free.

[0017] 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, assembly extract, angelica root 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, bupleurum falcatum, 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, 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.

[0018] 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.

[0019] 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. As a method for producing the external composition of the present invention, for example, a) minoxidil at 2 w / w% or more, b) tocopherol and / or its derivative, c) propylene glycol, and e) an acid are mixed to prepare a mixture, and f) water and d) a lower alcohol are added to the mixture to prepare the total amount; a method of mixing a) minoxidil at 2 w / w% or more, b) tocopherol and / or its derivative, c) propylene glycol, e) an acid, and f) water to prepare a mixture, and adding d) a lower alcohol to the mixture to prepare the total amount, etc. may be mentioned.

[0020] Examples, comparative examples, and reference examples are described below to explain the present invention more specifically, but the present invention is not limited by these examples etc.

Examples

[0021] (Example 1 and Comparative Examples 1, 2) The formulations of Example 1 and Comparative Examples 1 and 2 are shown in Table 1. Each component described in Table 1 was mixed, stirred, and dissolved, and ethanol was added to make the total amount 100 g to prepare a preparation.

[0022]

Table 1

[0023] (Test Method 1: Thermal Stability Test) After storing the test solutions of Example 1 and Comparative Examples 1 and 2 at 65 °C (relative humidity as it goes) for 7 days, the preparation was visually observed to confirm the color tone.

[0024]

Table 2

[0025] (Results) As is clear from Table 2, the minoxidil-containing preparation containing propylene glycol as the polyhydric alcohol (Example 1) did not show discoloration over time (colorless), but the minoxidil-containing preparations containing a polyhydric alcohol other than propylene glycol (Comparative Example 1 and Comparative Example 2) did show discoloration over time (slightly yellow).

[0026] (Examples 2-4 and Comparative Examples 3-5) The formulations for Examples 2-4 and Comparative Examples 3-5 are shown in Tables 3-4. Each component listed in Tables 3-4 was mixed and stirred to dissolve, and ethanol or purified water was added to make a total volume of 100 g.

[0027] [Table 3]

[0028] [Table 4]

[0029] (Test method 2: Thermal stability test) The test solutions of Examples 2-4 and Comparative Examples 3-5 were stored at 65°C (at ambient relative humidity) for 5 days, and the formulations were visually observed to confirm their color.

[0030] [Table 5]

[0031] As is clear from Table 5, the minoxidil-containing preparation containing propylene glycol as the polyhydric alcohol (Example 2) did not show discoloration over time (colorless), but the minoxidil-containing preparation containing a polyhydric alcohol other than propylene glycol (Comparative Example 3) did show discoloration over time (slightly yellow).

[0032] Furthermore, the minoxidil-containing preparation containing 20% ​​w / w ethanol (Comparative Example 4) became cloudy immediately after preparation. In addition, the minoxidil-containing preparations with 30% w / w or more ethanol (Examples 3 and 4) did not show discoloration over time (colorless), but the minoxidil-containing preparation with 25% w / w ethanol (Comparative Example 5) did show discoloration over time (slightly yellow).

[0033] (Prescription examples 1-50) Based on the following formulation examples, minoxidil-containing preparations were prepared in the same manner as in the examples.

[0034] [Table 6]

[0035] [Table 7]

[0036] [Table 8]

[0037] [Table 9]

[0038] The citric acid or phosphoric acid listed in the example formulation can be added in appropriate amounts within a range that does not cause any problems during manufacturing, and it is preferable to formulate it so that the pH is between 5.0 and 7.0. The amount of propyl gallate listed in the example formulation can be varied from 0.01% to 0.2% within a range that does not pose a manufacturing problem. The amount of BHT listed in the example formulation can be varied from 0.001% to 0.2% within a range that does not pose a manufacturing problem. [Industrial applicability]

[0039] The present invention makes it possible to provide a minoxidil-containing topical composition containing tocopherol and / or its derivatives that suppresses the discoloration of the formulation over time.

Claims

[Claim 1] The inventions described herein

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