JP2018048123A - 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

Description

    The present invention relates to an external composition containing minoxidil as an active ingredient. More specifically, a minoxidil-containing external composition containing at least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or a salt thereof, pantotenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or a salt thereof. The present invention relates to a technique for suppressing coloration over time.

Minoxidil has a chemical name of 6- (1-piperidinyl) -2,4-pyrimidinediamine-3-oxide and is known for its application as a hair restorer (Patent Document 1), and has excellent hair growth and hair growth effects. There are a number of reports on the drugs that exert.
In addition, glycyrrhetinic acid has an anti-inflammatory effect (Patent Document 2), pantotenyl ethyl ether has a cell activation effect (Patent Document 3), panthenol has a wound healing promoting effect (Patent Document 4), Hinokitiol has been reported to have an antibacterial action (Patent Document 5) and diphenhydramine has an itching inhibitory action (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 2000-1432 A Japanese Patent No. 5008162

  In order to develop an excellent hair restorer, the present inventors formulated a specific active ingredient, that is, glycyrrhetinic acid, pantotenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine hydrochloride in a composition containing minoxidil and an acid. When a minoxidil-containing composition for external use was produced and its stability was evaluated, it was surprisingly found that coloring was worse than that of a minoxidil single preparation by blending a specific active ingredient. The present invention provides a minoxidil-containing external composition containing at least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or a salt thereof, pantotenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or a salt thereof, It is an object of the present invention to provide a minoxidil-containing external composition that suppresses coloring of the preparation.

  Until now, between 2 w / w% or more of minoxidil and glycyrrhetinic acid and / or its salt, pantotenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine and / or its salt affects the color deterioration of the preparation There has been no report on whether such an interaction occurs.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have externally applied minoxidil containing glycyrrhetinic acid and / or a salt thereof, pantotenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine and / or a salt thereof. In the case of producing a composition, it was found that a minoxidil-containing composition for external use in which coloring of the preparation over time can be suppressed by selecting a specific polyhydric alcohol, and the present invention has been completed.

That is, the present invention
(1) a) 2 w / w% or more minoxidil,
b) At least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or a salt thereof, pantotenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or a salt thereof,
an external composition comprising c) propylene glycol and d) an acid;
(2) The composition for external use according to (1), wherein the concentration of minoxidil is 5 w / w% or more,
(3) a) 2% w / w or more minoxidil,
b) At least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or a salt thereof, pantotenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or a salt thereof,
c) mixing propylene glycol and d) acid to prepare 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 a total amount;
It 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 a salt thereof, pantotenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or a salt thereof. In the containing composition for external use, it became possible to provide a minoxidil-containing composition for external use in which coloring of the preparation over time was suppressed.

  According to the present invention, at least one active ingredient selected from the group consisting of 2 w / w% or more of minoxidil, glycyrrhetinic acid and / or its salt, pantotenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or its salt The composition for external use containing propylene glycol and acid suppresses coloring of the minoxidil preparation.

  As the minoxidil used in the composition for external use of the present invention, those having the quality usually used for pharmaceuticals can be appropriately used. 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 the amount is 5 w / w% or more, the coloring of the preparation further proceeds. Therefore, in the present invention, it is significant to carry out within this range.

  The polyhydric alcohol used in the composition for external use of the present invention is propylene glycol from the viewpoint of suppressing the coloration 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%, more preferably 2 to 35 w / w%, and further preferably 2 to 15 w / w% in the entire composition. The composition for external use of the present invention may contain a polyhydric alcohol other than propylene glycol as long as the effects of the present invention are not impaired. However, the effect of the present invention is better not blended with glycerin, polyethylene glycol or dipropylene glycol. From the point of view, it is most preferable to blend only propylene glycol from the viewpoint of the effect of the present invention.

  It is known to use acid to dissolve minoxidil in the base. The acid used in the external composition of the present invention is preferably a component that adjusts the liquidity of the external composition of the present invention to 7 or less, and includes an inorganic acid or an organic acid 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 are preferable, and phosphoric acid, citric acid, lactic acid, and tartaric acid are preferable. These acids may be used alone or in combination of two or more.

  In addition, the composition for external use of the present invention has a pH of 4.0 to 9.5 in terms of stability of minoxidil as the main ingredient, irritation to skin during use, drug permeability, use feeling, and the like. It is preferable to adjust to a range, and the range of 5.0-7.0 is further more preferable. Furthermore, as an upper limit of pH, Preferably it is less than 6.5, More preferably, it is 6.3 or less, More preferably, it is 6.1 or less.

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

  The external composition of the present invention can 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, hexyl decanol, isocetyl alcohol, More preferred are cetostearyl alcohol, heptadecanol, stearyl alcohol, oleyl alcohol, isostearyl alcohol, octyl decanol, nonadecanol, aralkyl alcohol, octyldodecanol, heicosanol, behenyl alcohol, decyltetradecanol, of which diacetone alcohol, Lauryl alcohol, myristyl alcohol, cetyl alcohol, hexyl decanol, cetostearyl alcohol Le, stearyl alcohol, isostearyl alcohol, oleyl alcohol, arachyl alcohol, octyldodecanol, behenyl alcohol, decyl tetradecanol 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%, more preferably 0.1 to 5 w / w%, still more preferably 0.25 to 1.5 w / w% in the external composition.

  If necessary, the composition for external use of the present invention may further contain a lower alcohol or water. As a lower alcohol, a C1-C5 thing is preferable, for example, ethanol, isopropanol, etc. are preferable, and you may use combining these. 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. is there. As for the compounding quantity of water, 2-75 w / w% is preferable, More preferably, it is 5-50 w / w%.

  The external composition of the present invention may further contain higher fatty acids as necessary. Examples of higher fatty acids are preferably 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, docosahexaenoic acid and the like, and these may be used alone or in combination. Of 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 entire composition.

  The external composition of the present invention may further contain a surfactant if necessary. However, the addition of a surfactant may affect the feeling of use and skin absorption of minoxidil, and the external composition of the present invention can ensure the solubility of minoxidil without adding a surfactant. It is preferable that the surfactant is not substantially contained.

  In the composition for external use of the present invention, various active ingredients and auxiliary components used for general external preparations can be blended within a range not impairing the effects of the present invention. For example, excipients, hair-growth ingredients (6-benzylaminopurine, adenosine, pentadecanoic acid glyceride, Natsutori, etc.), vasodilators (carpronium chloride, benzyl nicotinate, assembly extract, ginseng extract, chiketsujinjin tincture, Pepper tincture, etc.), antihistamines (isotipendil hydrochloride, etc.), anti-inflammatory agents (guaiazulene, etc.), keratolytic agents (urea, salicylic acid, etc.), bactericides (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, piroctone ora Mining, etc.), moisturizers (hyaluronic acid or its salts, chondroitin sulfate, etc.), various animals and plants (yew, button pi, licorice, hypericum, appendix, loquat, sagebrush, comfrey, ashitaba, saffron, sanshishi, rosemary, sage, mokko , Extracts from mokko, hops, placenta, saw palm, pumpkin seeds, vitamins (retinol acetate, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, etc.), antioxidants (dibutylhydroxytoluene, sodium pyrosulfite, tocopherol, edetic acid) Sodium, 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.), pressure-sensitive adhesives, fragrances, refreshing agents (mint oil, camphor, etc.), dyes and other commonly used components can be blended.

As an example of the dosage form of the composition for external use of this invention, a liquid agent, a lotion agent, etc. are mentioned.
Preparation of the composition for external use of this invention is prepared by containing said each component according to a conventional method.

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

  Examples of the method for producing an external composition of the present invention include: a) 2 w / w% or more of minoxidil, b) glycyrrhetinic acid and / or a salt thereof, pantotenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or a salt thereof. A method in which at least one active ingredient selected from the group consisting of c) propylene glycol, and d) an acid is mixed to prepare a mixture, and e) water and f) a lower alcohol are added to the mixture to prepare a total amount, a B) at least one active ingredient selected from the group consisting of 2% w / w minoxidil, b) glycyrrhetinic acid and / or its salt, pantotenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or its salt, c) Propylene glycol, d) acid, e) water to prepare a mixture, Added f) lower alcohol mixtures, including how to total amount prepared are exemplified by.

  Hereinafter, the present invention will be described more specifically with reference to examples, comparative examples, and reference examples. However, the present invention is not limited to these examples and the like.

(Examples 1 to 10, Comparative Examples 1 to 17 and Reference Example 1)
Formulations of Examples 1 to 10, Comparative Examples 1 to 17, and Reference Example 1 are shown in Tables 1 and 2. Each component described in Tables 1 and 2 was dissolved by mixing and stirring, and ethanol was added to prepare a preparation with a total amount of 100 g.

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

(result)
As is apparent from Table 3, coloring of the minoxidil-containing preparation (Example 1) in which propylene glycol was blended with polyhydric alcohol did not progress with time (colorless), but other than propylene glycol was blended with polyhydric alcohol. Coloring of the minoxidil-containing preparations (Comparative Examples 1 to 3) progressed with time (slight yellow).

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

(result)
As is apparent from Table 4, coloring of the minoxidil-containing preparation (Example 2) in which propylene glycol was blended with polyhydric alcohol did not proceed with time (colorless), but other than propylene glycol was blended with polyhydric alcohol. Coloring of the minoxidil-containing preparations (Comparative Examples 4 to 5) progressed with time (slight 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) for 5 days, the preparations were visually observed to confirm the color tone.

(result)
As is clear from Table 5, coloring of the minoxidil-containing preparations (Examples 3 to 10) in which propylene glycol was mixed with polyhydric alcohol did not progress with time (colorless), but other than propylene glycol was added to the polyhydric alcohol. Coloring of the blended minoxidil-containing preparations (Comparative Examples 6 to 17) progressed with time (slightly yellow or yellow).

  According to the present invention, a minoxidil-containing external composition containing at least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or a salt thereof, pantotenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and / or a salt thereof, It has become possible to provide a minoxidil-containing external composition that suppresses the coloration of the preparation over time.

Claims (2)

a) 2 w / w% or more minoxidil,
b) containing at least one active ingredient selected from the group consisting of glycyrrhetinic acid and / or its salt, pantotenyl ethyl ether, panthenol, hinokitiol, and diphenhydramine and / or its salt c) propylene glycol, and d) an acid The composition for external use characterized by doing. The composition for external use according to claim 1, wherein the concentration of minoxidil is 5 w / w% or more.