JP2022190158A - Composition for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: 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

COPYRIGHT: (C)2023,JPO&INPIT

Description

The present invention relates to an external composition containing minoxidil as an active ingredient. More specifically, a minoxidil-containing topical composition containing 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. The present invention relates to technology for suppressing coloration over time.

Minoxidil, whose chemical name is 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, is known to be applied as a hair restorer (Patent Document 1), and has excellent hair growth and growth effects. There are many reports as a drug that exerts
In addition, 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 been reported to have an antibacterial effect (Patent Document 5), and diphenhydramine has been reported to have an itch suppressing effect (Patent Document 6), and is used in many hair restorers.

U.S. Pat. No. 4,139,619 JP 2009-221190 A WO2007/074602 JP 2012-126733 A JP-A-2000-1432 Japanese Patent No. 5008162

In order to develop an excellent hair restorer, the present inventors formulated a composition containing minoxidil and an acid with specific active ingredients, namely glycyrrhetinic acid, pantothenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine hydrochloride. A topical composition containing minoxidil was produced and its stability was evaluated. Surprisingly, it was found that the formulation of a specific active ingredient exacerbated the coloration compared to a minoxidil preparation alone. The present invention provides a minoxidil-containing topical composition containing 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, An object of the present invention is to provide a minoxidil-containing composition for external use in which the coloring of the preparation is suppressed.

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, to affect the color exacerbation of the formulation There are no reported examples of whether such interactions occur.

As a result of intensive studies to solve the above problems, the present inventors have found a minoxidil-containing topical formulation containing glycyrrhetinic acid and/or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine and/or its salts. When manufacturing the composition, the inventors have found that by selecting a specific polyhydric alcohol, it is possible to manufacture a minoxidil-containing topical composition that suppresses coloration of the preparation over time, and have completed the present invention.

That is, the present invention
(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;
A topical composition comprising c) propylene glycol and d) an acid,
(2) The topical 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;
mixing c) propylene glycol, and d) an acid to form a mixture;
A method for producing a composition for external use, comprising the step of adding e) water and f) a lower alcohol to the mixture to prepare the total amount,
is.

According to the present invention, 2 w/w% or more minoxidil containing 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 a minoxidil-containing composition for external use in which the coloration of the formulation over time is suppressed in the composition for external use.

According to the present invention, 2 w/w% or more of at least one active ingredient selected from the group consisting of minoxidil, glycyrrhetinic acid and/or salts thereof, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or salts thereof , propylene glycol, and acid suppresses the coloring of minoxidil preparations.

As for minoxidil used in the composition for external use of the present invention, minoxidil of a quality commonly used in pharmaceuticals can be appropriately used. Also, 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. If the content is 5 w/w% or more, the coloration of the preparation progresses further, so it is significant to implement the content within this range in the present invention.

The polyhydric alcohol used in the composition for external use of the present invention is propylene glycol from the viewpoint of suppressing coloration of the formulation over time, which is the effect of the present invention. The blending amount of propylene glycol is preferably 2 to 55 w/w%, more preferably 2 to 35 w/w%, still more preferably 2 to 15 w/w% in the total composition. The composition for external use of the present invention may contain a polyhydric alcohol other than propylene glycol as long as it does not impair the effects of the present invention. From the point of view, it is most preferable from the point of view of the effect of the present invention to blend only propylene glycol.

It is known to use acids to dissolve minoxidil in bases. The acid used in the composition for external use of the present invention is preferably a component that adjusts the liquid property of the composition for external use to 7 or less, and includes inorganic acids and organic acids having 6 or less carbon atoms. Specifically, phosphoric acid, citric acid, lactic acid, hydrochloric acid, acetic acid, sulfuric acid, nitric acid, tartaric acid, maleic acid, malic acid and gluconic acid, preferably phosphoric acid, citric acid, lactic acid and tartaric acid. You may combine 1 type(s) or 2 or more types of these acids.

In addition, the composition for external use of the present invention has a pH of 4.0 to 9.5 from the viewpoints of the stability of minoxidil, which is the main ingredient, the feeling of irritation to the skin during use, the permeability of the drug, the feeling of use, etc. It is preferable to adjust it within a range, more preferably 5.0 to 7.0. Furthermore, the upper limit of the pH is preferably less than 6.5, more preferably 6.3 or less, still more preferably 6.1 or less.

The amount of glycyrrhetinic acid and/or a salt thereof used in the composition for external use of the present invention is preferably 0.01 to 1 w/w%, preferably 0.02, in the composition for external use from the viewpoint of suppressing the coloring of the present invention. It is more preferably 0.5 w/w%, still more preferably 0.05 to 0.1 w/w%, and preferably 0.02 parts by mass or more per 1 part by mass of minoxidil. The content of pantothenyl ethyl ether is preferably 0.1 to 5 w/w%, more preferably 0.2 to 2 w/w%, more preferably 0.2 to 2 w/w% in the composition for external use from the viewpoint of suppressing coloring of the present invention. 2 to 1 w/w% is more preferable, and 0.2 parts by mass or more is preferable with respect to 1 part by mass of minoxidil. The amount of panthenol is preferably 0.1 to 5 w/w%, more preferably 0.2 to 2 w/w%, and more preferably 0.2 to 0.2 to 1 w/w% is more preferable, and 0.2 parts by mass or more is preferable with respect to 1 part by mass of minoxidil. The content of hinokitiol is preferably 0.01 to 0.1 w/w%, more preferably 0.01 to 0.05 w/w%, more preferably 0.01 to 0.05 w/w% in the topical composition from the viewpoint of suppressing coloring of the present invention. 0.02 to 0.05 w/w% is more preferable, and 0.01 part by mass or more is preferable with respect to 1 part by mass of minoxidil. The amount of diphenhydramine and/or a salt thereof is preferably 0.01 to 1 w/w%, more preferably 0.02 to 0.5 w/w%, in the topical composition from the viewpoint of suppressing the coloring of the present invention. Preferably, 0.05 to 0.1 w/w% is more preferable, and 0.02 parts by mass or more is preferable with respect to 1 part by mass of minoxidil.

The composition for external use of the present invention may further contain a higher alcohol if necessary. Examples of higher alcohols include diacetone alcohol having 6 to 24 carbon atoms, caproyl alcohol, caprylyl alcohol, capryl alcohol, lauryl alcohol, tridecanol, myristyl alcohol, pentadecanol, cetyl alcohol, hexyldecanol, isocetyl alcohol, More preferred are cetostearyl alcohol, heptadecanol, stearyl alcohol, oleyl alcohol, isostearyl alcohol, octyldecanol, nonadecanol, arachyl alcohol, octyldodecanol, henicosanol, behenyl alcohol and decyltetradecanol, of which diacetone alcohol, More preferred are lauryl alcohol, myristyl alcohol, cetyl alcohol, hexyldecanol, cetostearyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, arachyl alcohol, octyldodecanol, behenyl alcohol and decyltetradecanol. You may use the higher alcohol of this invention 1 type or in combination of 2 or more types. The content of the higher alcohol is preferably 0.05 to 10 w/w%, more preferably 0.1 to 5 w/w%, even more preferably 0.25 to 1.5 w/w% in the composition for external use.

The composition for external use of the present invention may further contain a lower alcohol or water, if necessary. As the lower alcohol, those having 1 to 5 carbon atoms are preferred, such as ethanol and isopropanol, and these may be used in combination. The content of the lower alcohol in the entire composition is preferably 20 w/w% or more, more preferably 30 w/w% or more, more preferably 35 w/w% or more, still more preferably 50 w/w% or more. be. The blending amount of water is preferably 2 to 75 w/w%, more preferably 5 to 50 w/w%.

The composition for external use of the present invention may further contain a higher fatty acid if necessary. Examples of higher fatty acids 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, and elaidic acid. , arachidic acid, arachidonic acid, behenic acid, eicosapentaenoic acid, docosahexaenoic acid and the like, and these may be used singly or in combination of two or more. Among these, those having 18 carbon atoms are preferred, and isostearic acid or oleic acid is particularly preferred. The blending amount of the higher fatty acid is preferably 0.1 to 10 w/w%, more preferably 1 to 6 w/w%, in the total composition.

The composition for external use of the present invention may further contain a surfactant, if necessary. However, the addition of surfactants may affect the feeling of use and skin absorption of minoxidil, and in the composition for external use of the present invention, the solubility of minoxidil can be ensured without blending surfactants. , preferably substantially free of surfactants.

The composition for external use of the present invention can contain various active ingredients and auxiliary ingredients used in general external preparations, as long as they do not impair the effects of the present invention. For example, excipients, hair-growth ingredients (6-benzylaminopurine, adenosine, pentadecanoic acid glyceride, Hekkei bird, etc.), vasodilators (carpronium chloride, benzyl nicotinate, assembly extract, panax ginseng extract, 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, piroctoneola) min, etc.), moisturizing agents (hyaluronic acid or its salts, chondroitin sulfate, etc.), various animals and plants (yew, botanpi, licorice, hypericum perforatum, Bushi, loquat, artemisia var. , Seymong, hops, placenta, saw palmetto, pumpkin seed, etc.), vitamins (retinol acetate, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, etc.), antioxidants (dibutyl hydroxytoluene, sodium pyrosulfite, tocopherol, edet) sodium acid, 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 (highly water-soluble molecules, etc.), adhesives, fragrances, refreshing agents (mint oil, camphor, etc.), dyes, and other commonly used ingredients can be blended.

Examples of dosage forms of the composition for external use of the present invention include liquids and lotions.
The composition for external use of the present invention is prepared according to a conventional method by containing each of the above components.

The composition for external use of the present invention thus obtained can be used as a preparation for skin application such as a preparation for hair, a preparation for eyelashes and a preparation for eyebrows.

As a method for producing the composition for external use of the present invention, for example, a) 2 w/w% or more of minoxidil, b) glycyrrhetinic acid and/or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or its salts A method of preparing a mixture by mixing 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 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) For example, propylene glycol, d) an acid, and e) water are mixed to prepare a mixture, and f) a lower alcohol is added to the mixture to prepare the total amount.

Examples, Comparative Examples, and Reference Examples are described below to describe the present invention in more detail, but the present invention is not limited by these Examples and the like.

(Examples 1 to 10, Comparative Examples 1 to 17 and Reference Example 1)
The formulations of Examples 1-10, Comparative Examples 1-17 and Reference Example 1 are shown in Tables 1-2. Each component shown in Tables 1 and 2 was mixed, stirred and dissolved, and ethanol was added to adjust the total amount to 100 g to prepare a formulation.

(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. (relative humidity) for 3 days, the formulations were visually observed to confirm the color tone.

(result)
As is clear from Table 3, the coloring of the minoxidil-containing preparation (Example 1) in which propylene glycol was blended with the polyhydric alcohol did not progress over time (colorless), but the polyhydric alcohol other than propylene glycol was blended. Minoxidil-containing formulations (Comparative Examples 1 to 3) developed coloration over time (pale yellow).

(Test method 2: Thermal stability test-2)
After storing the test liquids of Example 2 and Comparative Examples 4 and 5 at 65° C. (relative humidity) for 5 days, the formulations were visually observed to confirm the color tone.

(result)
As is clear from Table 4, the coloring of the minoxidil-containing preparation (Example 2) in which propylene glycol was blended with the polyhydric alcohol did not progress over time (colorless), but the polyhydric alcohol other than propylene glycol was blended. The coloration of minoxidil-containing preparations (Comparative Examples 4 and 5) progressed over time (pale yellow).

In addition, even with the same faint yellow color, the preparation with a higher concentration of glycyrrhetinic acid showed a stronger color tone.

(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 trend) for 5 days, the formulations were visually observed to confirm the color tone.

(result)
As is clear from Table 5, the coloring of the minoxidil-containing formulations (Examples 3 to 10) in which propylene glycol was blended with the polyhydric alcohol did not progress over time (colorless), but when the polyhydric alcohol other than propylene glycol was used, the coloration did not progress over time. The coloration of the formulations containing minoxidil (Comparative Examples 6 to 17) progressed over time (pale yellow or yellow).

According to the present invention, a minoxidil-containing topical composition containing 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 a minoxidil-containing composition for external use that suppresses coloration of the formulation over time.

Claims (1)

The invention described in the specification.