JP2018162319A - Composition for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a minoxidil-containing external composition having improved precipitation derived from minoxidil, which may occur after application. It has been found that by blending menthol, it is possible to improve the precipitation of minoxidil-derived material that may occur after application in a minoxidil-containing external composition. That is, it is an external composition characterized by containing 2 w / w% or more of minoxidil, menthol, a specific acid and / or a salt thereof, and propylene glycol. [Selection diagram] None

Description

  The present invention relates to an external composition containing minoxidil as an active ingredient. More specifically, the present invention relates to a technique for suppressing precipitation derived from minoxidil which may be caused by application of a minoxidil-containing external composition.

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.
Since the minoxidil-containing external composition is used daily for a long period of time on the head, there is a demand for a composition that is excellent in use feeling. When a composition having a high concentration of minoxidil is used, deposits derived from minoxidil rarely occur after application and may appear as dandruff. Therefore, in a composition for external use in which minoxidil is blended, a composition that suppresses precipitation derived from minoxidil that may occur after coating is desired.
On the other hand, menthol is used as a cooling agent in many preparations.

U.S. Pat. No. 4,139,619

  This invention makes it a subject to provide the minoxidil containing external composition which suppressed the precipitation derived from the minoxidil which may arise after apply | coating about a minoxidil containing external composition.

  As a result of intensive studies to solve the above problems, the present inventors have found that a composition containing minoxidil, a specific acid and / or salt thereof, a specific polyhydric alcohol, and menthol has a precipitate derived from minoxidil. The inventors have found that it can be suppressed, and have completed the present invention.

That is, the present invention
(1) (a) 2 w / w% or more minoxidil, (b) menthol, (c) phosphoric acid, citric acid, lactic acid, hydrochloric acid, acetic acid, sulfuric acid, nitric acid, tartaric acid, gluconic acid, and maleic acid A minoxidil-containing external composition comprising at least one selected acid and / or a salt thereof, and (d) propylene glycol,
(2) The composition for external use according to (1), wherein the concentration of (a) minoxidil is 5 w / w% or more,
It is.

  INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a minoxidil-containing external composition that suppresses the precipitation derived from minoxidil that may occur after applying the minoxidil-containing external composition. Furthermore, surprisingly, it can be provided as a clear minoxidil-containing external composition that does not cause precipitation in the preparation.

  According to the present invention, a composition for external use containing minoxidil, menthol, a specific acid and / or salt thereof, and a specific polyhydric alcohol suppresses the precipitation derived from minoxidil which may occur after coating, In this case, no precipitate is formed.

  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. In addition, according to the present invention, as the content of minoxidil increases, the problem of precipitation that may occur after the formulation is applied increases. Therefore, the higher the concentration of minoxidil in the composition for external use, the greater the significance of carrying out the present invention. Is big. Specifically, 2 w / w% or more is preferable in the composition for external use of this invention, 3 w / w% or more is more preferable, Most preferably, it is 5 w / w% or more.

  The specific acid and / or salt thereof 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 from the viewpoint of the effect of the present invention that a clear preparation without precipitation is obtained. , Tartaric acid, gluconic acid, maleic acid, or salts thereof. Of 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 salts thereof are components for adjusting the liquidity of the composition for external use of the present invention to 7 or less, and all are inorganic acids or salts thereof or organic acids having 6 or less carbon atoms or salts thereof. . The specific acid and / or salt thereof of the present invention may be used alone or in combination.

  The polyhydric alcohol used in the external composition of the present invention is propylene glycol. The blending amount of propylene glycol is preferably 2 to 55 w / w%, more preferably 5 to 35 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, but glycerin and polyethylene glycol are preferably not blended from the viewpoint of the effects of the present invention, It is most preferable to blend only propylene glycol from the viewpoint of the effect of the present invention.

  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 content of menthol used in the composition for external use of the present invention is preferably 0.05 to 2 w / w%, more preferably 0.1 to 1.5 w / w% in the composition for external use from the viewpoint of the effect of the present invention.

  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 2 w / w%, more preferably 0.1 to 1.5 w / w%, and even more preferably 0.25 to 2.5% in the composition for external use from the viewpoint of the effect of the present invention. 1.5 w / w%.

  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 the skin absorption of minoxidil, and the lotion of the present invention can provide a sufficient precipitation improving effect without the addition of a surfactant. It is preferable that the surfactant is not substantially contained.

  To the composition for external use of the present invention, necessary active ingredients and auxiliary ingredients can be added in addition to the above-described components as long as the effects of the present invention are not impaired. Preferred medicinal ingredients to be added to and blended with 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. It is done. The addition amount of these selective components is not particularly limited, and can be determined experimentally in consideration of the feeling in use, the stability of minoxidil or the solvent composition.

  In the composition for external use of the present invention, in addition to the above-described components, 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.

  The composition for external use of the present invention can be a suitable composition for external use such as lotion, aerosol, tonic, cream, ointment, gel and the like. Among these, the most preferable dosage form is a lotion agent.

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 Examples, comparative examples, and test examples will be described below, and the present invention will be described more specifically. However, the present invention is not limited by these examples.

(Reference Example 1)
Minoxidil (5 g), propylene glycol (15 g), purified water (20 g), an appropriate amount of phosphoric acid, ethanol was adjusted to a total amount of 100 g, and the mixture was stirred for about 1 hour to obtain an external composition having a pH of 6.1.

(Reference Example 2)
Minoxidil (2 g), propylene glycol (15 g), purified water (20 g), a suitable amount of phosphoric acid, and ethanol were adjusted to a total amount of 100 g, followed by stirring for about 1 hour to obtain an external composition having a pH of 5.8.

(Reference Example 3)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, appropriate amount of citric acid, ethanol was adjusted to 100 g, and stirred for about 1 hour to obtain an external composition having a pH of 6.1.

(Reference Example 4)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, appropriate amount of lactic acid, and ethanol to make the total amount 100 g, stirred for about 1 hour to obtain a pH 6.0 external composition.

(Reference Example 5)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, appropriate amount of tartaric acid, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to obtain an external composition having a pH of 6.0.

Example 1
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, appropriate amount of phosphoric acid, menthol 0.3 g, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to obtain a pH 6.1 external composition.

(Example 2)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, citric acid appropriate amount, menthol 0.3 g, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to obtain a pH 6.1 external composition.

(Example 3)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, appropriate amount of lactic acid, menthol 0.3 g, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to obtain a pH 6.0 external composition.

Example 4
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, hydrochloric acid appropriate amount, menthol 0.3 g, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to obtain a pH 6.0 external composition.

(Example 5)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, appropriate amount of acetic acid, 0.3 g of menthol, and 100 g of total amount with ethanol were stirred for about 1 hour to obtain an external composition having a pH of 6.1.

(Example 6)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, appropriate amount of sulfuric acid, 0.3 g of menthol, ethanol was adjusted to 100 g, and stirred for about 1 hour to obtain an external composition having a pH of 6.0.

(Example 7)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, appropriate amount of nitric acid, 0.3 g of menthol, ethanol was adjusted to 100 g, and the mixture was stirred for about 1 hour to obtain an external composition having a pH of 6.0.

(Example 8)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, tartaric acid appropriate amount, menthol 0.3 g, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to obtain a pH 6.0 external composition.

Example 9
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, appropriate amount of gluconic acid, menthol 0.3 g, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to obtain a pH 6.0 external composition.

(Example 10)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, appropriate amount of maleic acid, 0.3 g of menthol, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to obtain an external composition having a pH of 6.0.

(Example 11)
Minoxidil (2 g), propylene glycol (15 g), purified water (20 g), phosphoric acid appropriate amount, menthol (0.3 g), ethanol was adjusted to 100 g, and the mixture was stirred for about 1 hour to obtain an external composition having a pH of 5.8.

(Comparative Example 1)
Minoxidil 5 g, polyethylene glycol 400 15 g, purified water 20 g, phosphoric acid appropriate amount, menthol 0.3 g, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to obtain a pH 6.3 external composition.

(Comparative Example 2)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, dl-malic acid appropriate amount, menthol 0.3 g, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to prepare a composition for external use having a pH of 6.0.

(Comparative Example 3)
Minoxidil 5 g, propylene glycol 15 g, purified water 20 g, boric acid appropriate amount, menthol 0.3 g, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to prepare an external composition having a pH of 6.0.

(Comparative Example 4)
Minoxidil 2 g, polyethylene glycol 400 15 g, purified water 20 g, phosphoric acid appropriate amount, menthol 0.3 g, ethanol was adjusted to 100 g in total, and stirred for about 1 hour to prepare an external composition having a pH of 5.9.

<Test Example 1: Precipitation test-1>
With respect to Reference Example 1, Example 1, and Comparative Example 1, 100 μL each of the composition for external use was dropped on a glass petri dish, and after 24 hours, crystal precipitation derived from minoxidil was visually evaluated. The results are shown in Table 1. A sample in which precipitation was improved as compared with Reference Example 1 was marked with ◯, and a sample in which precipitation was not improved was marked with x. The test was performed three times.

  In Reference Example 1 in which propylene glycol was blended, crystal precipitation derived from minoxidil was confirmed, but Example 1 in which menthol was blended was improved. On the other hand, in Comparative Example 1 in which polyethylene glycol was blended as a polyhydric alcohol, precipitation was not improved.

<Test Example 2: Precipitation test-2>
About 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 the composition for external use was dropped on each glass plate, After 24 hours, crystal precipitation derived from minoxidil was visually evaluated. The results are shown in Table 2. The case where the precipitation improvement effect superior to the reference example was recognized was evaluated as ◎, the case where the precipitation improvement effect was recognized as ○, and the case where the precipitation improvement effect was not recognized as ×. The test was performed three times.

  In Reference Examples 2 to 5 blended with propylene glycol, crystal precipitation derived from minoxidil was confirmed, but Examples 2, 3, 8 and 11 blended with menthol were improved. On the other hand, in Comparative Example 4 in which polyethylene glycol was blended as a polyhydric alcohol, precipitation was not improved.

<Test Example 3: Preparation test of lotion agent>
With respect to the lotion preparations of Examples 1 to 10 and Comparative Examples 2 to 3, preparation preparation tests were performed. Immediately after the preparation, the lotion agent in the beaker was visually confirmed, and a clear product without a precipitate was obtained as “◯”, and a product in which a precipitate was produced was marked as “X”. The results are shown in Table 3.

  As is apparent from Table 3, in Examples 1 to 10 using the acid of the present invention, all the components were dissolved, and a clear lotion without a precipitate was obtained. On the other hand, when malic acid or boric acid was used, a precipitate was formed in the lotion agent (Comparative Examples 2 and 3).

  INDUSTRIAL APPLICABILITY According to the present invention, in a minoxidil-containing external composition, it is possible to provide an excellent minoxidil-containing external composition that suppresses precipitation from minoxidil that may occur after coating and suppresses precipitation in the external composition. Became.

Claims (2)

(A) 2 w / w% or more of minoxidil, (b) menthol, (c) at least 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 A minoxidil-containing external composition comprising one kind of acid and / or a salt thereof and (d) propylene glycol. The external composition according to claim 1, wherein the concentration of (a) minoxidil is 5 w / w% or more.