JPH08277209A - Revitalizing hair tonic - Google Patents

Abstract

PURPOSE: To obtain an excellent revitalizing hair tonic by using monoxidil and a monoalkyl ether of an aliphatic polyalcohol as a transdermal absorption enhancer for monoxidil. CONSTITUTION: The transdermal absorption of monoxidil is increased by using an aliphatic monoalkylether of an aliphatic polyalcohol. Glycerin is preferred as aliphatic polyalcohol. α-Monoisostearylglycerylether is preferred as a monoalkyl ether of an aliphatic polyalcohol. In a preferred formulation, 0.5-5%.wt. of monoxidil [chemical name: 6-(1-piperidinyl)-2,4-pirimidiamine-3- oxide] is used. The amount of monoalkylether of aliphatic polyalcohol in the formulation is preferably in 1-20%.wt. This revitalizing hair tonic is used as lotion, tonic, cream, ointment and aerosol.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hair-growth agent having increased transdermal absorbability of minoxidil.

[0002]

Minoxidil has a chemical name of 6- (1-piperidinyl) -2,4-pyrimidinediamine-3-oxide, and its application as a hair restorer is described in U.S. Pat. No. 4,139,619. In the US patent publication, a formulation example in which propylene glycol is added as a base component is described. However, since the skin has resistance to drug permeation, when minoxidil is used as an external preparation, there is a drawback that it is difficult to absorb a sufficient amount to exert its drug effect. Therefore, in recent years, attempts have been made to improve the transdermal absorbability of minoxidil as a preparation, but the transdermal absorbability of minoxidil has been poor in the hitherto known preparations, and for various types of alopecia of various types. Was not sufficiently effective.

[0003]

SUMMARY OF THE INVENTION In view of the above circumstances, an object of the present invention is to provide a hair-growth agent which increases the transdermal absorbability of minoxidil, and in which a sufficient amount of minoxidil to exert a drug effect is transdermally absorbed. is there.

[0004]

As a result of earnest research, the present inventors have found that a monoalkyl ether of an aliphatic polyhydric alcohol significantly enhances the transdermal absorbability of minoxidil, and completed the present invention. That is, the present invention is a hair restorer characterized by containing minoxidil and a monoalkyl ether of an aliphatic polyhydric alcohol.

In the present invention, the aliphatic polyhydric alcohol is a divalent or trivalent alcohol having 2 to 6 carbon atoms. Glycerin, hexanetriol, ethylene glycol, and the like are preferable as the aliphatic polyhydric alcohol.
Propylene glycol, 1,4-butanediol, triethylene glycol, diethylene glycol and the like can be mentioned, and glycerin is most preferable. Further, the alkyl group which forms an ether bond with the aliphatic polyhydric alcohol is preferably a linear or branched alkyl group having 8 to 24 carbon atoms. When the carbon chain is shorter than 8, the skin irritation is increased and it is not preferable as an external preparation, and when the carbon chain is longer than 24, the fluidity is deteriorated and the formulation becomes difficult. Octyl group, nonyl group, decyl group, dodecyl group, tetradecyl group, cetyl group, stearyl group, isostearyl group to the preferred alkyl group,
Examples thereof include eicosanyl group and docosanyl group, and the most preferable one is isostearyl group.

In the aliphatic polyhydric alcohol, the hydroxyl group forming an ether bond with the alkyl group may be a hydroxyl group at any site, but a hydroxyl group at the terminal of the fatty chain with an ether bond is most preferred.

As a matter of course, the monoalkyl ether of the aliphatic polyhydric alcohol used in the present invention must have high safety when used as an external preparation.

In the present invention, the content of minoxidil is preferably 0.1 to 5% by weight, more preferably 0.5 to 2% by weight, based on the whole preparation. The compounding amount of the monoalkyl ether of the aliphatic polyhydric alcohol is preferably 1 to 20% by weight, more preferably 2 to 10% by weight. As other ingredients, excipients usually used in hair restorers,
Vasodilators (carpronium chloride, benzyl nicotinate, senburi extract, ginseng extract, vitamin E acetate, capsicum tincture, etc.), corticosteroids (hydrocortisone acetate, hydrocortisone propionate butyrate, etc.), antihistamines (diphenhydramine hydrochloride, isothipendyl hydrochloride, etc.) , Anti-inflammatory agents (glycyrrhetinic acid, guaizulene, etc.), keratolytic agents (urea, salicylic acid, etc.), bactericides (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, hinokitiol, piroctone olamine, etc.), moisturizers (Sodium hyaluronate, glycerin,
Chondroitin sulphate, etc.), extracts of various plants and animals (yew, button pipi, licorice, St. John's wort, konjac, loquat, sagebrush, comfrey, ashitaba, saffron, sardine, rosemary, sage, mokko, samokko, hops, placenta, etc.), vitamins Kinds (retinol acetate, pyridoxine hydrochloride, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, etc.), oil (isopropyl myristate, isopropyl palmitate, squalane, liquid paraffin, lecithin, etc.), surfactant (polyoxyethylene sorbitan fatty acid ester, Sorbitan fatty acid ester, polyoxyethylene fatty acid ester, glycerin fatty acid ester, propylene glycol fatty acid ester, polyoxyethylene hydrogenated castor oil, etc.), polyhydric alcohol Le (propylene glycol, 1,
3-butanediol, macrogol, dipropylene glycol, etc.), essential oils (menthol, camphor, etc.), antioxidants (dibutylhydroxytoluene, isopropyl gallate, etc.), sequestering agents (ethylenediaminetetraacetate or its salts), dyes, Fragrances and the like can be added within a range that does not impair the effects of the composition of the present invention.

The hair restorer of the present invention can be prepared according to a conventional method from external preparations such as lotions, tonics, creams, ointments and aerosols.

The hair restorer of the present invention is applied to the scalp in an appropriate amount once to several times a day for use.

[0011]

As is apparent from the test examples described below, the present invention has made it possible to provide a hair-growing agent with improved transdermal absorbability of minoxidil.

[0012]

EXAMPLES The present invention will be described in detail below based on examples and test examples.

Example 1 80 parts by weight of ethanol, 0.5 parts by weight of minoxidil, α
-2% by weight of monoisostearyl glyceryl ether and 17.5 parts by weight of purified water were added and dissolved by stirring to prepare a lotion type hair restorer.

According to the adjusting method described in Example 1, the hair-growing agents of Examples 2 to 4 and Control Examples 1 and 2 were prepared according to the formulations shown in Table 1.

[0015]

[Table 1]

Example 5 42.7 parts by weight of purified water were mixed with 0.
4 parts by weight were dispersed with stirring. 40 parts by weight of ethanol, 5 parts by weight of 1,3-butanediol, 1 part by weight of minoxidil, 10 parts by weight of α-monoisostearyl glyceryl ether, 0.5 part by weight of L-menthol and 0.4 part by weight of diisopropanolamine. A solution in which the parts were dissolved by stirring was added and mixed by stirring to prepare a gel-type hair restorer.

Example 6 Polyoxyethylene (20) sorbitan monostearate 5 parts by weight, sorbitan monostearate 3 parts by weight, cetanol 2 parts by weight, stearyl alcohol 2 parts by weight, liquid paraffin 10 parts by weight and vitamin E acetate 0. 2 parts by weight and 2 parts by weight of α-monoisostearyl glyceryl ether were mixed and dissolved while heating. Separately, 1 part by weight of minoxidil, 0.1 part by weight of hinokitiol, 0.2 part by weight of glycyrrhetinic acid, 0.05 part by weight of dibutylhydroxytoluene, 0.05 part by weight of ethylenediaminetetraacetate-2 sodium salt, methyl paraoxybenzoate of 0.1 part by weight. A solution in which 05 parts by weight and 74.35 parts by weight of purified water were dissolved and stirred while heating was added, and the mixture was cooled to room temperature with mixing and stirring to prepare a cream type hair restorer.

Example 7 Minoxidil 2 parts by weight, pantotenyl ethyl ether 0.1 parts by weight, assembly extract 0.1 parts by weight, α-monoisostearyl glyceryl ether 2 parts by weight, polyoxyethylene hydrogenated castor oil 0.5 parts by weight. Part, ethanol 60
A lotion type hair restorer was prepared by stirring and dissolving 3 parts by weight of purified water and 35.3 parts by weight of purified water.

Example 8 5 parts by weight of minoxidil, 10 parts by weight of propylene glycol, 10 parts by weight of α-monoisostearyl glyceryl ether, 65 parts by weight of ethanol and 10 parts by weight of purified water were mixed and dissolved to give a lotion type hair restorer. Prepared.

Example 9 0.5 part by weight of minoxidil, 2 parts by weight of glycerin, 2 parts by weight of polyoxyethylene (20) polyoxypropylene (6) decyl tetradecyl ether, 1 part by weight of gypsum extract, and carrot extract 0.1. By weight, 10 parts by weight of α-monoisostearyl glyceryl ether, 60 parts by weight of ethanol and 24.4 parts by weight of purified water were dissolved by stirring to prepare a lotion-type hair restorer.

Example 10 Minoxidil 2 parts by weight, ethinyl estradiol 0.
0008 parts by weight, capsicum tincture 0.5 parts by weight, nicotinic acid amide 0.2 parts by weight, polyoxyethylene (6)
0.5 parts by weight of monooleate, 4 parts by weight of dipropylene glycol, 5 parts by weight of α-monoisostearyl glyceryl ether, 0.01 part by weight of peppermint oil, 0.005 part by weight of dibutylhydroxytoluene, 60 parts by weight of ethanol,
27.7842 parts by weight of purified water was dissolved by stirring to prepare a lotion type hair restorer.

Example 11 Minoxidil 1 part by weight, isopropylmethylphenol 0.05 part by weight, 1,3-butanediol 5 parts by weight, α
5 parts by weight of monoisostearyl glyceryl ether, 0.5 parts by weight of polyoxyethylene (20) hydrogenated castor oil,
55 parts by weight of ethanol and 33.45 parts by weight of purified water were dissolved by stirring. 50 parts by weight of this solution was placed in an aerosol can, and 50 parts by weight of dimethyl ether was charged under pressure to prepare an aerosol type hair restorer.

Example 12 2 parts by weight of minoxidil, 0.1 part by weight of glycyrrhetinic acid, 0.1 part by weight of hinokitiol, 0.2 part by weight of vitamin E acetate, 0.1 part of pantotenyl ethyl ether.
5 parts by weight, isothipendyl hydrochloride 0.5 part by weight, pyridoxine hydrochloride 0.1 part by weight, placenta extract 0.1 part by weight, octyldodecyl myristate 0.5 part by weight, L-
0.05 parts by weight of menthol, 1 part by weight of glyceryl monooleate, 1 part by weight of sorbitan monolaurate, 20 parts by weight of α-monoisostearyl glyceryl ether, 50 parts by weight of ethanol and 24.2 parts by weight of purified water were dissolved by stirring. To prepare a lotion type hair restorer.

Example 13 2 parts by weight of stearic acid, 1.5 parts by weight of cetanol, 3 parts by weight of white petrolatum, 2 parts by weight of lanolin alcohol, 2 parts by weight of polyoxyethylene (10) monooleate, α-
5 parts by weight of monoisostearyl glyceryl ether and 0.2 parts by weight of vitamin E acetate were mixed and dissolved while heating. 0.5 parts by weight of minoxidil, 0.2 parts by weight of glycyrrhetinic acid, and 0.0 parts of methyl paraoxybenzoate.
5 parts by weight, 0.05 parts by weight of ethylenediamine tetraacetate-2 sodium salt, 10 parts by weight of propylene glycol, and 73.5 parts by weight of purified water were added and dissolved in a liquid,
While mixing, the mixture was cooled to room temperature to prepare an emulsion type hair restorer.

Test Example [Minoxidil Transdermal Absorption Test] The abdominal skin of Wistar rats (7 weeks old, male) was excised, and the receiver side was brought into contact with the back surface of the skin in a glass diffusion cell (effective area 0.95 cm ² ). So it was installed. To the receiver, 3 ml of pH 7.4 phosphate buffer was added, and the temperature was kept at 37 ° C by circulating water. The surface side of the skin was left open, 5 μl of the samples of Examples 1 to 4 and Controls 1 and 2 were applied, and the amount of minoxidil permeated into the receiver solution was measured by a high performance liquid chromatography method.
The test result shows that the ratio of the amount of permeation of the sample of the example when the amount of the sample of the comparative example was 100% with respect to the amount of permeation 24 hours after the start of the test (for example 1 and example 2, comparative example 1, example 3 and Example 4 was described as Comparative Example 2). The results are shown in Table 2.

[0026]

[Table 2]

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location A61K 47/04 A61K 47/04 E 47/14 47/14 E (72) Inventor Fumio Urushizaki Tokyo 3-24-1 Takada, Toshima-ku, Taisho Pharmaceutical Co., Ltd.

Claims (3)

[Claims] 1. A hair restorer containing minoxidil and a monoalkyl ether of an aliphatic polyhydric alcohol. 2. The hair restorer according to claim 1, wherein the aliphatic polyhydric alcohol is glycerin. 3. The hair restorer according to claim 1, wherein the monoalkyl ether of the aliphatic polyhydric alcohol is α-monoisostearyl glyceryl ether.