JPS62230710A - Hair tonic composition - Google Patents

Abstract

PURPOSE:To obtain a hair-tonic composition adsorbable in a short time and exhibiting sufficient hair-tonic effect with small dose, by using minoxidil having hair-tonic effect in combination with a specific transcutaneous absorbefacient such as 7-15C alcohol, thereby promoting the transcutaneous adsorption of minoxidil. CONSTITUTION:A hair-tonic composition having the above effects can be produced by compounding a hair-tonic composition containing minoxidil with a 7-15C alcohol, a (halogen-substituted) 5-30C aliphatic hydrocarbon, an alkyl ester of a 13-24C aliphatic carboxylic acid, an N-alkylmorpholine, a 1-3C alcohol diester of a 4-10C dicarboxylic acid, a lactam, a nicotinic acid ester, a monoester of an alkylene glycol and an aliphatic carboxylic acid, an aliphatic hydrocarbon ester of a 1-alkyl-2-pyrrolidone-5-carboxylic acid, a glycerol monoester of a 10-18C carboxylic acid, a proline ester, an N-alkylproline ester and/or cineole. The transcutaneous absorbability of minoxidil can be remarkably improved by the process.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a hair nourishing composition that can enhance transdermal absorption of minoxidil.

[Conventional technology]

The problem of hair growth has become more and more serious as the social structure has become more complex in recent years. Therefore, many hair growth agents are being developed and researched. In recent years, the antihypertensive drug minoxidil (i.e., 2,4-diamino-6-biperidinopyrimidine-3
- oxide) is reported to have a hair-nourishing effect.

[Problem that the invention seeks to solve]

By the way, since hair tonics are usually in the form of lotions, they need to be absorbed in a short period of time to exert their effects, but this is still not sufficient due to their insufficient absorbency. Furthermore, since minoxidil has antihypertensive effects, it is desirable to use it in as small a quantity as possible.

Therefore, an object of the present invention is to provide a hair-growth composition that increases the transdermal absorption of minoxidil, allows minoxidil to be absorbed in a short period of time, and exhibits a sufficient hair-growth effect even with the administration of a small amount of minoxidil.

[Means for solving problems]

As a result of extensive research to solve these problems, the present inventors have found that if minoxidil is administered to the outer skin in the presence of the transdermal absorption promoting aids mentioned below, the transdermal absorption of minoxidil is improved. It was found that this was significantly improved.

The present invention has been completed based on the above-mentioned new findings, and its gist is that it contains minoxidil and at least one transdermal absorption promoting aid selected from (1) to (10) below. This invention relates to a hair nourishing composition.

The percutaneous absorption promoting agent is as follows: ■ Alcohol having 7 to 15 carbon atoms, ■ Aliphatic hydrocarbon having 5 to 30 carbon atoms which may be substituted with halogen, ■ Alcohol having 13 to 24 carbon atoms in total. Alkyl ester of aliphatic carboxylic acid, ■N-alkylmorpholine, ■C1-3 alcohol diester of dicarboxylic acid having 4-10 carbon atoms (5)
Lactams, ■ Nicotinic acid ester, ■ Monoester of alkylene glycol and aliphatic carboxylic acid, ■ Aliphatic hydrocarbon ester of 1-alkyl-2-pyrrolidone-5-carboxylic acid, (10) Glycerin with 10 or more carbon atoms 18
carboxylic acid monoester, (1) proline ester or N-alkylproline ester, @cineol.

Each of the transdermal absorption promoting aids ① to ＠ used in the present invention will be explained.

(2) Alcohol having 7 to 15 carbon atoms: The alcohol may be linear, branched, or cyclic, and may be saturated or unsaturated. Therefore, it also includes terpene alcohols, sesquiterpene alcohols, and the like. Such alcohols include n-heptyl alcohol, n-decyl alcohol, lauryl alcohol, 2-ethylhexyl alcohol, linalyl alcohol, geranyl alcohol, dimethyl octatool, nerol, citronellol, farnesol, nerolidol, terpineol, borneol, thymol, and the like. Examples include alcohols. Particularly preferred are aliphatic alcohols.

■Aliphatic hydrocarbon having 5 to 30 carbon atoms which may be substituted with halogen: The aliphatic hydrocarbon may be linear, branched or cyclic.The halogen as a substituent is bromine,
Chlor is preferred.

The aliphatic hydrocarbon moiety has 5 carbon atoms in the case of a chain.
An alkyl group having ~30 (preferably 6 to 24) saturated or 1 or 2 unsaturated bonds is preferred,
In the case of a cyclic structure, monocyclic or bicyclic ones are preferable; in the case of a monocyclic structure, the number of carbon atoms is preferably 6 to 10;
The above methyl may be substituted with Wl-alkyl,
Alternatively, two or more monocycles may be bonded via alkylene (eg, methylene, ethylene, etc.). In the case of two rings, the number of carbon atoms is preferably 10 to 12, and it may be substituted with, for example, one or more lower alkyl having 1 to 4 carbon atoms, such as methyl.

Specifically, the compounds include n-pentane, n-hexane, n-hebutane, n-octane, n-nonane, n-
-decane, n-undecane, n-dodecane, n-tetradecane, n-hexadecane, n-octadecane, 2-methyl-pencune, 2-methylhexane, 2,3-dimethylhexane, 2-methylnonane, 2,6-cyclo Octane, 2,2,4゜4.6,8.8-heptamethylnonane, bristane, squalane, light liquid paraffin, paramethane, limonene, hydrogenated product of limonene dimer, cyclohexane, 1,3-dimethylcyclohexane, cyclooctane , isobutylcyclohexane, cyclododecane, methyldecalin, decalin, octyl bromide,
Examples include decyl bromide, dodecyl bromide, hexadecyl bromide, dodecyl chloride, dibromdodecane, and the like.

(1) Alkyl ester of aliphatic carboxylic acid having a total of 13 to 24 carbon atoms, preferably 13 to 18 carbon atoms: The ester has the general formula Ra COORb (1) (wherein, Ra represents an aliphatic group and Rb represents an alkyl group. , the total number of carbon atoms of Ra and Rb is 12 to 23).

Here, the aliphatic group represented by Ra is preferably a chain type, and may be either saturated or unsaturated. Particularly preferred are those derived from fatty acids having 12 to 18 carbon atoms, particularly those derived from saturated fatty acids having 12 carbon atoms.

Examples of the alkyl represented by Rh include methyl,
Ethyl, n-propyl, 1so-propyl, n-butyl, tso-butyl, 5ee-butyl, t-butyl, n-
1 or more carbon atoms such as amyl, 1so-amyl, n-hexyl, etc.
6 is preferred.

Specific examples of the ester include methyl laurate, ethyl laurate, hexyl laurate, isopropyl myristate, isopropyl palmitate, butyl stearate, methyl oleate, ethyl linoleate, ethyl T-linoleate, and the like. be done.

(2) N-Alkylmorpholine The compound is particularly preferably N-alkylmorpholine (II) represented by the following general formula (wherein R represents an alkyl having 7 to 14 carbon atoms).

In the general formula (II), the alkyl having 7 to 14 carbon atoms may be linear or branched, and examples include n-heptyl, n-octyl, n-nonyl, 2-ethylhexyl, and tetradecyl. . Specific examples of N-alkylmorpholine (■) include N-octylmorpholine, N-decylmorpholine, N-dodecylmorpholine, N-tetradecylmorpholine, and 2-ethylhexylmorpholine.

(1) Alkyl ester having 1 to 3 carbon atoms of dicarboxylic acid having 4 to 10 carbon atoms The dicarboxylic acid having 4 to 10 carbon atoms is preferably an aliphatic dicarboxylic acid, and may be either saturated or unsaturated;
Further, it may be either linear or branched, but preferably saturated and linear.

Examples of such dicarboxylic acids include adipic acid, sebacic acid, maleic acid, and fumaric acid.

Examples of the alkyl in the alkyl ester include methyl, ethyl, n-propyl, and the like. The alkyl ester may have two carboxyl groups substituted with the same alkyl group, or may have two carboxyl groups substituted with different alkyl groups.

Preferred examples of the ester include diisopropyl adipate, diethyl sebacate, and the like.

■ Lactams As lactams, those having 4 to 7 atoms forming a ring are preferable, such as β-proviolactam, T-butyrolactam, ε-caprolactam, and δ-valerolactam.
The 8-lactams may have a substituent, and the substituent is preferably an alkyl group, particularly one having 5 to 20 carbon atoms, preferably 7 to 16 carbon atoms, such as dodecyl, heptyl, octyl, hexadecyl, etc. is exemplified. The substituent is preferably substituted at the N-position of the lactam ring.

Preferred examples of the lactams include 1-dodecyl azacycloheptanone and -dodecylpyrrolidone.

(2) Nicotinic acid ester In the present invention, nicotinic acid ester (III) represented by the general formula (wherein Re represents an alkyl group having 5 or more carbon atoms) is particularly used.

-IG formula ([[[), carbon number represented by Rc is 5
The above alkyl may be saturated, unsaturated, chain, or cyclic. The alkyl preferably has 6 to 24 carbon atoms. The number of carbon atoms in the saturated alkyl group is preferably 5 to 20,
For example, n-pentyl, n-octyl, n-nonyl, n
- Straight chain ones such as decyl, n-undecyl, n-dodecyl, n-tetradecyl, n-hexadecyl, n-octadecyl, n-eicosyl, 2-methylhexyl, 2-
Examples include branched ones such as ethylhexyl, 3.7-dimethyloctyl, 2-hexyldecyl, 2-octyldodecyl, 2,4.4-trimethyl-1-pentyl, and -methyloctyl. Unsaturated alkyl has 6 to 2 carbon atoms
4 is preferred, and examples thereof include cis-3-hexenyl, oleyl, lylyl and the like. The total carbon number of the cyclic alkyl is particularly preferably 6 to 12, such as 2-cyclohexylethyl, cyclohebutyl, cyclohexylmethyl,
Reasonable alkyls include cyclooctyl, 4-cyclohexylbutyl, 3-cyclopentylpropyl, 5-methyl-2-isopropylcyclohexyl, etc., and the simple number forming the cyclic portion is 6 to 8, that is, a 6 to 8-membered ring. preferable.

■ Monoester of alkylene glycol and aliphatic carboxylic acid The alkylene group in the alkylene glycol used in the present invention is preferably ethylene or propylene, and the aliphatic carboxylic acid has 6 to 22 carbon atoms, preferably 10 to 10 carbon atoms. Eighteen fatty acids are used. The aliphatic carboxylic acid may be saturated or unsaturated, and examples thereof include capric acid, lauric acid, myristic acid, and oleic acid.

Preferred monoesters of alkylene glycol and aliphatic carboxylic acids include propylene glycol monolaurate, propylene glycol monomyristate, and the like.

■Aliphatic hydrocarbon ester of 1-alkyl-2-pyrrolidone-5-carboxylic acid (l-alkyl PCA ester) The aliphatic hydrocarbon ester part of 1-alkyl PCA ester has about 1 to 24 carbon atoms. preferable,
Examples of the esters include alkyl esters and unsaturated hydrocarbon esters. The alkyl in the alkyl ester may be cyclic, that is, cycloalkyl, or may be chain (either linear or branched). Furthermore, the unsaturated hydrocarbon group in the unsaturated hydrocarbon ester may be linear, branched, or cyclic. The chain alkyl preferably has 1 to 20 carbon atoms, and the cyclic alkyl preferably has 6 to 12 carbon atoms. Unsaturated hydrocarbon ester has 6 to 2 carbon atoms
4 is preferred, and it may be either chain or cyclic. The 'unsaturated group contained therein is preferably a double bond, and the number thereof is preferably 1 or 2.

Examples of the alkyl group in the alkyl moiety at position 1 include methyl, ethyl, n-propyl, 1so-propyl, n-
Those having 1 to 5 carbon atoms, such as butyl, t-butyl, 1so-amyl, and n-amyl, are preferred.

Specifically, the chain alkyl esters include 1-alkylpyrrolidonecarboxylic acid methyl ester, ■-alkylpyrrolidonecarboxylic acid ethyl ester, ■-alkylpyrrolidonecarboxylic acid n-propyl ester, and 1-alkylpyrrolidonecarboxylic acid n-butyl ester. ester, 1-alkyl and lolidone carboxylic acid n-heptyl ester, 1
-Alkylpyrrolidonecarboxylic acid n-octyl ester, 1-alkylpyrrolidonecarboxylic acid n-nonyl ester, 1-alkylpyrrolidonecarboxylic acid n-decyl ester, ■-alkylpyrrolidonecarboxylic acid n-undecyl ester, 1-alkylpyrrolidonecarboxylic acid n-dodecyl ester, 1-alkylpyrrolidonecarboxylic acid n
-1-lysosyl ester, 1-alkylpyrrolidonecarboxylic acid n-tetradecyl ester, 1-alkylpyrrolidonecarboxylic acid n-hexadecyl ester, 1-alkylpyrrolidonecarboxylic acid n-octadecyl ester, ■
-Alkylpyrrolidonecarboxylic acid n-eicosyl ester, 1-alkylpyrrolidonecarboxylic acid 1so-propyl ester, 1-alkylpyrrolidonecarboxylic acid 2-methylhexyl ester, 1-alkylpyrrolidonecarboxylic acid 2-ethylhexyl ester, l-alkylpyrrolidone Carboxylic acid 3,7-dimethyloctyl ester, 1
-Alkylpyrrolidonecarboxylic acid 2-hexyldecyl ester, 1-alkylpyrrolidonecarboxylic acid 2-octyldodecyl ester, l-alkylpyrrolidonecarboxylic acid 2,4.4-trimethyl 1-pencune ester, l-
Straight chain and branched ones such as alkylpyrrolidone carboxylic acid methyloctyl ester are mentioned. The alkyl in l-alkyl in the above compound is methyl, ethyl, n-propyl, 1so-propyl, n-butyl,
n-amyl, 1so-amyl, etc.

As the cyclic alkyl ester, 1-alkylpyrrolidone carbon #2-cyclohexylethyl ester, 1-
Alkylpyrrolidonecarboxylic acid cycloheptyl ester, 1-alkylpyrrolidonecarboxylic acid cycloheptyl ester, 1-alkylpyrrolidonecarboxylic acid cyclooctyl ester, 1-alkylpyrrolidonecarboxylic acid 4-cyclohexylbutyl ester, l-alkylpyrrolidonecarboxylic acid 3 -cyclopentylpropyl ester, l-alkylpyrrolidonecarboxylic acid 5-methyl-2-isopropylcyclohexyl ester, and the like. The alkyl in 1-alkyl in the above compound includes methyl, ethyl, n-propyl, 1so-propyl, n-butyl, n-amyl, 1so-amyl, and the like.

Examples of unsaturated hydrocarbon esters include 1-alkylpyrrolidonecarboxylic acid-cis-3-hexyl ester, 1-
Alkylpyrrolidone carboxylic acid-oleyl ester, 1
-Alkylpyrrolidone carboxylic acid sulfyl ester, etc. In the above compounds, 1-alkyl is methyl, ethyl, n-propyl, 1so-
These include propyl, n-butyl, dooramyl, 1so-amyl, and the like.

Examples of unsaturated hydrocarbon esters include esters derived from terpene alcohols, and specific examples include 1-alkylpyrrolidonecarboxylic acid geranyl esters, in which case the number of carbon atoms in the terpene alcohol is 10 to 20. The alkyl in 1-alkyl in the above compound is preferably methyl, ethyl, n-propyl, 1so-propyl, n-butyl, n
-amyl, 1so-amyl, etc.

(10) Carboxylic acid monoester having 10 to 18 carbon atoms of glycerin The carboxylic acid having 10 to 18 carbon atoms is preferably an aliphatic carboxylic acid, and may be either saturated or unsaturated, for example,
Fatty acids are preferred, and examples of the aliphatic acids include capric acid, lauric acid, myristic acid, and oleic acid.

Specific examples of the ester include glycerin monocabrilate, glycerin monolaurate, glycerin monomyristate, and glycerin monooleate.

■Proline ester or N-alkylproline ester The compound used in the present invention has the general formula (wherein R
d represents a hydrogen atom or an aliphatic hydrocarbon group, Re represents an aliphatic hydrocarbon residue, and the total number of carbon atoms of Rd and Re is 2.
0 or less) [hereinafter, the compound is also referred to as proline ester (rV)].

Regarding general 20V), the aliphatic hydrocarbon groups represented by Rd and Re may be either saturated or unsaturated, or may be linear, branched, or cyclic. The aliphatic hydrocarbon residue preferably has about 1 to 20 carbon atoms, and the total number of carbon atoms of Rd and Re is 20 or less. When the aliphatic hydrocarbon group is an unsaturated group, the unsaturated bond contained is preferably a double bond, and the number of unsaturated bonds is preferably 1 to 2, and in the case of a cyclic group. The number of carbon atoms is preferably 5 to 12, and the number of rings is preferably one, preferably a 5 to 7-membered ring.

Aliphatic hydrocarbon groups in Rd include methyl, ethyl, n-propyl, 1so-propyl, n-butyl, 5
ec-butyl, tert-butyl, n-amyl, 1so
- Lower alkyl having 1 to 5 carbon atoms such as amyl is preferred.

Examples of aliphatic hydrocarbon residues related to Re include:
n-hexyl, n-hebutyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-
tridecyl, n-tetradecyl, n-hexadecyl, n
- Saturated chain substances having 6 to 18 carbon atoms such as octadecyl, 2-methylhexyl, 2-ethylhexyl, 3.7-dimethyloctyl, 2-hexyldecyl, 2-cyclohexylethyl, cycloheptyl, cyclohexylmethyl, Saturated cyclic substances having 6 to 12 carbon atoms such as 4-cyclohexylbutyl and 3-cyclopentylpropyl, ci
Unsaturated compounds having 6 to 18 carbon atoms are preferred, such as s-3-hexenyl, 2-decenyl, oleyl, menthyl, and geranyl.

Specific examples of proline ester (IV) include N-methylproline lauryl ester, proline heptyl ester, N-ethylproline tetradecyl ester, and the like.

Proline ester (IV) may be used as a salt thereof, and there are no particular restrictions on the salt as long as it is pharmacologically acceptable.
Tartaric acid, succinic acid, maleic acid, fumaric acid, etc.), inorganic fa (eg, mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.).

@Cineol The blending amount of minoxidil in the hair nourishing composition of the present invention is as follows:
As long as the amount is sufficient to exhibit a hair-restoring effect (it varies depending on the patient's symptoms, dosage form, etc., and may be selected appropriately depending on the conditions. For example, about 0.1 to 10% by weight) .

The amount of the absorption-promoting agent to be blended may be sufficient to promote transdermal absorption of minoxidil, and although it varies depending on the dosage form, it is usually 0.01 to 2% of the total amount of the preparation.
It is preferably about 0% by weight, particularly about 0.2 to 10% by weight.

Incidentally, since the area to which the composition of the present invention is applied to the skin varies depending on the patient, it is not necessarily limited to the above-mentioned amount.

The compositions of the present invention can be prepared by adding known pharmaceutically acceptable ingredients (e.g., bases, excipients, stabilizers, colorants, etc.) to ointments, plasters, lotions, adhesive tapes, impregnating agents, and gels. It is used as a hair lotion, hair tonic, hair cream, shampoo, etc., or by applying it to the inner wall of a wig.

[Effect]

The composition of the present invention has the effect of promoting transdermal absorption of minoxidil by the absorption-enhancing agent blended therein, so the composition of the present invention enhances the transdermal absorption of minoxidil, and thus absorbs minoxidil in a short period of time. Minoxidil is absorbed, can be made into a lotion-type product, and even a small amount of minoxidil can have sufficient hair-nourishing effects.
It is highly safe.

〔Example〕

Examples 1 to 20 The basic recipe is 44.5% ethanol (95”), 44% purified water
4.5%, minoxidil 1%, and the following 1 to 20
A preparation was prepared in which 10% of each of the accelerators shown below was added.

Table 1 1, linalyl alcohol 2, lauryl alcohol 3, n-nonane 4, n-dodecane 5, dibromidodecane 6, isopropyl myristate 7, methyl oleate 8, N-dodecylmorpholine 9, N-nonylmorpholine 1O, Methyl laurate 11, diisopropyl adipate 12. 1-dodecyl azacycloheptanone 13. 1-dodecylpyrrolidone 14, nicotinic acid lauryl ester 15. Propylene glycol monolaurate 16, N-
Methylpyrrolidone carboxylic acid lauryl 17, cineole 18, glycerin monolaurate 19, N-methylproline lauryl ester 20, proline lauryl ester comparative example Among the components of Examples 1 to 20, excluding the transdermal absorption enhancer,
A mixture of 49.5% ethanol and 49.5% purified water and 1% minoxidil dissolved therein was used.

Experimental Example Rough) Part III The skin was excised, and the part corresponding to the surface of the skin was in contact with the compositions of Examples 1 to 20 and Comparative Examples above,
The rat skin was attached to a glass transmission cell so that the back side of the skin was in contact with the saline, and minoxidil that had permeated into the saline was quantified using high performance liquid chromatography. Note that this test was conducted in a sealed container. The obtained results were calculated as the acceleration rate 2 A/B A: Amount of drug permeated through the skin in the example formulation B: Amount of drug permeated through the skin layer in the comparative example formulation, and the results are shown in Table 1.

Table 1 [Effects] The hair growth composition in which a transdermal absorption enhancer is added to minoxidil according to the present invention has 10.3 to 35.0 times more excellent skin permeation than a composition without a transdermal absorption enhancer. Thus, minoxidil is absorbed in a short period of time, and even a small amount of minoxidil administered can exhibit a sufficient hair-nourishing effect.

Claims (1)

[Scope of Claims] A hair growth composition comprising minoxidil and at least one transdermal absorption promoting aid selected from the following (1) to (12). (1) Alcohol having 7 to 15 carbon atoms, (2) Aliphatic hydrocarbon having 5 to 30 carbon atoms optionally substituted with halogen, (3) Alkyl ester of aliphatic carboxylic acid having 13 to 24 total carbon atoms , (4) N-alkylmorpholine (5) C1-C3 alcohol diester of C4-C10 dicarboxylic acid, (6) Lactams, (7) Nicotinic acid ester, (8) Alkylene glycol and aliphatic monoesters with carboxylic acids, (9) aliphatic hydrocarbon esters of 1-alkyl-2-pyrrolidone-5-carboxylic acids, (1
0) C10-18 carboxylic acid monoester of glycerin, (11) proline ester or N-alkylproline ester, (12) cineole.