External use ingredients

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 a topical composition containing minoxidil as an active ingredient. More specifically, the present invention relates to a technique for suppressing precipitation derived from minoxidil that may occur upon application of a topical composition containing minoxidil. [Background technology]

[0002] Minoxidil has the chemical name 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, and is known to be applicable as a hair growth agent (Patent Document 1). There have been many reports of it being a drug that exhibits excellent hair growth and hair regrowth effects. Since a minoxidil-containing topical composition is used on the scalp every day for a long period of time, a composition that is excellent in usability is required. When a composition with a high concentration of minoxidil is used, precipitation of minoxidil may occur after application, which may look like dandruff. Therefore, a composition that suppresses the precipitation of minoxidil that may occur after application in a topical composition containing minoxidil 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] U.S. Pat. No. 4,139,619 Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide a minoxidil-containing topical composition for topical use that inhibits precipitation derived from minoxidil that may occur after application. [Means for solving the problem]

[0005] As a result of intensive research aimed at solving the above-mentioned problems, the inventors have found that a composition containing minoxidil, a specific acid and / or a salt thereof, a specific polyhydric alcohol, and menthol can inhibit precipitation derived from minoxidil, and have thus completed the present invention.

[0006] That is, the present invention provides: (1) A minoxidil-containing topical composition comprising (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) (a) The composition for external use according to (1), wherein the concentration of minoxidil is 5 w / w% or more; It is. Effect of the Invention

[0007] According to the present invention, it is possible to provide a minoxidil-containing topical composition that suppresses precipitation derived from minoxidil that may occur after application of the minoxidil-containing topical composition. Furthermore, unexpectedly, it is possible to provide a clear minoxidil-containing topical composition that does not generate precipitates in the formulation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] According to the present invention, a topical composition containing minoxidil, menthol, a specific acid and / or its salt, and a specific polyhydric alcohol inhibits precipitation derived from minoxidil that may occur after application, and does not produce precipitates in the formulation.

[0009] The minoxidil used in the topical composition of the present invention can be of the quality generally used in pharmaceutical products.In addition, according to the present invention, the higher the content of minoxidil, the greater the problem of precipitation that may occur after application of the preparation, so the higher the concentration of minoxidil in the topical composition, the greater the significance of carrying out the present invention.Specifically, the concentration of minoxidil in the topical composition of the present invention is preferably 2w / w% or more, more preferably 3w / w% or more, and most preferably 5w / w% or more.

[0010] From the viewpoint of the effect of the present invention that a clear preparation without precipitation can be obtained, the specific acid and / or its salt in the composition for external use 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 their salts. Among these, phosphoric acid, citric acid, lactic acid, and tartaric acid are preferred, and phosphoric acid and lactic acid are most preferred. These acids and / or their salts are components that adjust the liquidity of the composition for external use of the present invention to 7 or less, and are all inorganic acids or their salts, or organic acids or their salts having 6 or less carbon atoms. The specific acids and / or their salts of the present invention may be used alone or in combination of two or more.

[0011] The polyhydric alcohol used in the topical composition of the present invention is propylene glycol. The amount of propylene glycol in the total composition is preferably 2 to 55 w / w%, more preferably 5 to 35 w / w%. The topical composition of the present invention may contain a polyhydric alcohol other than propylene glycol within a range that does not impair the effects of the present invention, but it is preferable not to include glycerin or polyethylene glycol in the composition from the viewpoint of the effects of the present invention, and it is most preferable to include only propylene glycol in the composition from the viewpoint of the effects of the present invention.

[0012] In addition, the pH of the topical composition of the present invention is preferably adjusted to a range of 4.0 to 9.5, more preferably 5.0 to 7.0, from the viewpoints of the stability of the main ingredient minoxidil, the irritation to the skin during use, the permeability of the drug, the feeling of use, etc. Furthermore, 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.

[0013] The content of menthol used in the topical composition of the present invention is preferably 0.05 to 2 w / w %, and more preferably 0.1 to 1.5 w / w %, in the topical composition in terms of the effects of the present invention.

[0014] The composition for external use of the present invention may further contain a higher alcohol 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, arachidyl alcohol, octyldodecanol, henicosanol, behenyl alcohol, and decyl tetradecanol, which have 6 to 24 carbon atoms, and among these, diacetone alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, hexyl decanol, cetostearyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, arachidyl alcohol, octyldodecanol, behenyl alcohol, and decyl tetradecanol are more preferred. The higher alcohols of the present invention may be used alone or in combination of two or more. In terms of the effects of the present invention, the content of the higher alcohol in the composition for external use is preferably 0.05 to 2 w / w%, more preferably 0.1 to 1.5 w / w%, and even more preferably 0.25 to 1.5 w / w%.

[0015] The composition for external use of the present invention may further contain lower alcohol or water as necessary. The lower alcohol is preferably one having 1 to 5 carbon atoms, such as ethanol or isopropanol, and may be used in combination. The content of the lower alcohol is preferably 20 w / w% or more of the total composition, more preferably 30 w / w% or more, more preferably 35 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%.

[0016] The composition for external use of the present invention may further contain a higher fatty acid if necessary. Examples of higher fatty acids include those having 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, and may be used alone or in combination of two or more. Among these, those having 18 carbon atoms are preferred, and isostearic acid or oleic acid are particularly preferred. The amount of higher fatty acid is preferably 0.1 to 10 w / w% of the total composition, and more preferably 1 to 6 w / w%.

[0017] The topical composition of the present invention may further contain a surfactant if necessary. However, the addition of a surfactant may affect the feel of use and the skin absorption of minoxidil, and since the lotion of the present invention can obtain a sufficient precipitation improvement effect without the incorporation of a surfactant, it is preferable that the lotion does not substantially contain a surfactant.

[0018] In addition to the above-mentioned components, the composition for external use of the present invention may contain necessary active ingredients and auxiliary ingredients within the range that does not impair the effects of the present invention. Examples of medicinal ingredients that are preferably added or blended into the lotion of the present invention include ingredients selected from the group consisting of vitamin E acetate, pantothenyl ethyl ether, hinokitiol, pyridoxine hydrochloride, glycyrrhetinic acid, diphenhydramine hydrochloride, and panthenol. The amount of these optional ingredients to be added is not particularly limited, and can be determined experimentally while taking into consideration the feeling of use, the stability of minoxidil, the composition of the solvent system, etc.

[0019] In addition to the above-mentioned components, the topical composition of the present invention may contain various active ingredients and auxiliary ingredients used in general topical preparations, provided that the effects of the present invention are not impaired. For example, excipients, hair growth ingredients (6-benzylaminopurine, adenosine, pentadecanoic acid glyceride, Polygonum polycutrum, etc.), vasodilators (carpronium chloride, benzyl nicotinate, Swertia japonica extract, Panax ginseng extract, Panax 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.), moisturizers (hyaluronic acid or its salts, chondroitin sulfate, etc.), various plants and animals (yew, moutan pi, licorice, Hypericum perforatum, aconite, loquat, artemisia capillaris, comfrey, angelica tree, saffron). It can contain commonly used ingredients such as extracts of Japanese laurel, rosemary, sage, bamboo shoots, Japanese laurel, 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.), solubilizers (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, refreshing agents (peppermint oil, camphor, etc.), dyes, etc.

[0020] The topical composition of the present invention can be in the form of a suitable topical composition such as a lotion, aerosol, tonic, cream, ointment, gel, etc. Among these, the most preferred dosage form is a lotion.

[0021] The composition for external use of the present invention can be prepared by incorporating the above-mentioned components in a conventional manner. The thus obtained composition for external use of the present invention can be used as a preparation for application to the skin, such as a preparation for hair, eyelashes, or eyebrows.

[0022] The present invention will be explained in more detail below with reference to examples, comparative examples and test examples, but the present invention is not limited to these examples in any way. 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use having 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use having 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use having 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 ethanol were added to make a total of 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use having 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use having 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use 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 ethanol were added to make a total of 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use 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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to obtain a composition for external use with a pH of 6.3.

[0040] Comparative Example 2 A composition for external use having a pH of 6.0 was prepared by mixing 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 ethanol to a total weight of 100 g, and stirring for approximately 1 hour.

[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 ethanol were added to bring the total weight to 100 g, and the mixture was stirred for about 1 hour to prepare a composition for external use with a pH of 6.0.

[0042] Comparative Example 4 A composition for external use of 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 ethanol was added to bring the total weight to 100 g, and stirred for about 1 hour to prepare a composition for external use with a pH of 5.9.

[0043] <Test Example 1: Precipitation Test-1> For Reference Example 1, Example 1, and Comparative Example 1, 100 μL of each of the compositions for external use 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. The one in which the precipitation was improved compared to Reference Example 1 was marked with ○, and the one in which the precipitation was not improved was marked with ×. The test was performed three times.

[0044] [Table 1]

[0045] In Reference Example 1, which contained propylene glycol, crystal precipitation derived from minoxidil was observed, but this was improved in Example 1, which contained menthol. On the other hand, in Comparative Example 1, which contained polyethylene glycol as the polyhydric alcohol, the precipitation was not improved.

[0046] <Test Example 2: Precipitation Test-2> For 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 each of the compositions for external use 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. The one that showed an excellent precipitation improvement effect compared to the reference example was marked with ◎, the one that showed an precipitation improvement effect was marked with ○, and the one that did not show an precipitation improvement effect was marked with ×. The test was performed three times.

[0047] [Table 2]

[0048] In Reference Examples 2 to 5, which contained propylene glycol, crystal precipitation derived from minoxidil was observed, but this was improved in Examples 2, 3, 8, and 11, which contained menthol. On the other hand, in Comparative Example 4, which contained polyethylene glycol as the polyhydric alcohol, precipitation was not improved.

[0049] <Test Example 3: Preparation test of lotion> Preparation tests were carried out for the lotions of Examples 1 to 10 and Comparative Examples 2 to 3. Immediately after preparation, the lotions in the beakers were visually inspected, and clear preparations without precipitates were marked with an O, and preparations with precipitates in the lotions were marked with an X. The results are shown in Table 3.

[0050] [Table 3]

[0051] As is clear from Table 3, in Examples 1 to 10 in which the acid of the present invention was used, all of the ingredients were dissolved, and clear lotions without precipitate were obtained. On the other hand, when malic acid or boric acid was used, precipitates were generated in the lotions (Comparative Examples 2 and 3). [Industrial Applicability]

[0052] According to the present invention, it is now possible to provide an excellent minoxidil-containing topical composition for topical use that inhibits precipitation derived from minoxidil that may occur after application and suppresses the formation of precipitates in the topical composition.

Claims

1. An additive comprising menthol for inhibiting precipitation derived from minoxidil that occurs after application of an external pharmaceutical composition containing (a) minoxidil, (b) tartaric acid, and (c) 5 to 35 w / w % propylene glycol, The pharmaceutical composition for external application contains 20 w / w % or more of ethanol and 2 to 75 w / w % of water, and does not contain polyethylene glycol; The pH of the pharmaceutical composition for external application after adding the additive is 5.0 to 7.0; The amount of menthol in the topical pharmaceutical composition after adding the additive is 0.3 g per 5 g of minoxidil.

2. The additive according to claim 1, which is added to the external pharmaceutical composition so that the blending amount of menthol is in the range of 0.05 to 2 w / w %.

3. The additive according to claim 1 or 2, wherein the concentration of minoxidil in the topical pharmaceutical composition is 5 w / w% or more.

4. A method for inhibiting precipitation derived from minoxidil that occurs after application of an external pharmaceutical composition, comprising adding menthol to the external pharmaceutical composition containing (a) minoxidil, (b) tartaric acid, and (c) 5 to 35 w / w % propylene glycol, The pharmaceutical composition for external application contains 20 w / w % or more of ethanol and 2 to 75 w / w % of water, and does not contain polyethylene glycol; The pH of the pharmaceutical composition for external use after adding menthol is 5.0 to 7.0; The method, wherein the amount of menthol in the topical pharmaceutical composition after adding menthol is 0.3 g per 5 g of minoxidil.

5. The method according to claim 4, wherein menthol is added so that the amount of menthol in the pharmaceutical composition for external use falls within the range of 0.05 to 2 w / w %.

6. The method according to claim 4 or 5, wherein the concentration of minoxidil in the topical pharmaceutical composition is 5 w / w% or more.

7. A use of menthol to inhibit precipitation derived from minoxidil that occurs after application of an external pharmaceutical composition containing (a) minoxidil, (b) tartaric acid, and (c) 5 to 35 w / w % propylene glycol, comprising: The pharmaceutical composition for external application contains 20 w / w % or more of ethanol and 2 to 75 w / w % of water, and does not contain polyethylene glycol; The pH of the pharmaceutical composition for external use after adding menthol is 5.0 to 7.0; The amount of menthol in the topical pharmaceutical composition after adding menthol is 0.3 g per 5 g of minoxidil.

8. The use according to claim 7, wherein menthol is added so that the amount of menthol in the external pharmaceutical composition is in the range of 0.05 to 2 w / w %.

9. The use according to claim 7 or 8, wherein the concentration of minoxidil in the topical pharmaceutical composition is 5 w / w% or more.

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