JPH072628B2 - Hair nourishing composition - Google Patents

Description

TECHNICAL FIELD The present invention relates to a hair nourishing composition capable of enhancing percutaneous absorption of minoxidil.

[Conventional technology]

The problem of hair growth has become more and more serious as the social structure has become complicated in recent years. Therefore, many hair restorers have been developed and studied. Minoxidil (ie, 2,4-diamino-6-piperidinopyrimidine-3-
Oxide) is reported to have a hair-growth effect.

[Problems to be solved by the invention]

By the way, since hair nourishing agents are usually used such as lotion type, it is necessary to absorb them in a short period of time to exert their effects, but it cannot be said to be sufficient because its absorbability is insufficient. Since minoxidil has an antihypertensive effect, it is desirable to use it in a small amount as much as possible.

Therefore, it is an object of the present invention to provide a hair nourishing composition that enhances the transdermal absorbability of minoxidil, and thus absorbs minoxidil in a short time, and exerts a sufficient hair nourishing effect by administration of a small amount of minoxidil.

[Means for solving problems]

The present inventors have conducted extensive studies to solve such problems, and when minoxidil is administered to the outer skin in the presence of the transdermal absorption-promoting auxiliary agents described below, the transdermal absorbability of minoxidil becomes remarkable. It has been found to be improved.

The present invention has been completed based on the above new findings, and the gist thereof is to contain minoxidil and at least one percutaneous absorption enhancer selected from the following: Regarding

The transdermal absorption accelerating aids are as follows: alcohol having 7 to 15 carbon atoms, aliphatic hydrocarbon having 5 to 30 carbon atoms which may be substituted with halogen, total carbon number
Alkyl esters of 13-24 aliphatic carboxylic acids, N-
Alkyl morpholine, alcohol diester having 4 to 10 carbon atoms and dicarboxylic acid having 1 to 3 carbon atoms, lactams,
Nicotinic acid ester, monoester of alkylene glycol and aliphatic carboxylic acid, 1-alkyl-2-
They are an aliphatic hydrocarbon ester of pyrrolidone-5-carboxylic acid, a carboxylic acid monoester of glycerin having 10 to 18 carbon atoms, a proline ester or an N-alkylproline ester, and cineol.

Each of the transdermal absorption-promoting aids used in the present invention will be described.

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 alcohol, sesquiterpene alcohol and the like. Examples of the alcohol include monohydric alcohols such as n-heptyl alcohol, n-decyl alcohol, lauryl alcohol, 2-ethylhexyl alcohol, linalyl alcohol, geranyl alcohol, dimethyloctanol, nerol, citronellol, farnesol, nerolidol, terpineol, borneol and thymol. Examples include alcohol. Aliphatic monohydric alcohols are particularly preferred.

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

The aliphatic hydrocarbon moiety has 5 carbon atoms when it is chain-like.
~ 30 (preferably 6-24) saturation or 1 or 2
An alkyl group having one unsaturated bond is preferable, and in the case of a cyclic group, a monocyclic or bicyclic group is preferable. In the case of a monocyclic ring, the number of carbon atoms is preferably 6 to 10, which is one or more methyl, May be substituted with saturated or unsaturated alkyl having 1 to 3 carbon atoms. Also, two or more monocycles may be bonded via alkylene (eg, methylene, ethylene, etc.). In the case of two rings, it preferably has 10 to 12 carbon atoms, which is, for example, 1 to 1 carbon atoms, such as methyl.
4 may be substituted with lower alkyl.

Specific examples of the compound include n-pentane, n-hexane, n-heptane, n-octane, n-nonane, and n.
-Decane, n-undecane, n-dodecane, n-tetradecane, n-hexadecane, n-octadecane, 2-methyl-pentane, 2-methylhexane, 2,3-dimethylhexane, 2-methylnonane, 2,6-dimethyl Octane, 2,2,4,4,6,8,8-heptamethylnonane, pristane, squalane, light liquid paraffin, paraffin, limonene, hydrogenation product of limonene dimer, cyclohexane, 1,3-dimethylcyclohexane, cyclooctane ,
Isobutyl cyclohexane, cyclododecane, methyl decalin, decalin, octyl bromide, decyl bromide, dodecyl bromide, hexadecyl bromide,
Dodecyl chloride and dibrom dodecane are examples.

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

Here, the aliphatic group represented by Ra is preferably a chain group, and may be saturated or unsaturated. In particular,
Those derived from fatty acids having 12 to 18 carbon atoms, especially those derived from saturated fatty acids having 12 carbon atoms are preferable.

Examples of alkyl represented by Rb include, for example, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso.
-Butyl, sec-butyl, t-butyl, n-amyl, iso
-Amyl, n-hexyl and the like having 1 to 6 carbon atoms are preferable.

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

N-alkylmorpholine As the compound, in particular, the following general formula (In the formula, R represents alkyl having 7 to 14 carbon atoms), and N-alkylmorpholine (II) is preferable.

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

C1 to C3 alkyl ester of C4 to C10 dicarboxylic acid The C4 to C10 dicarboxylic acid is preferably an aliphatic dicarboxylic acid, which may be saturated or unsaturated, and may be straight chain, It may be branched, but is preferably saturated or linear. Examples of such dicarboxylic acid include adipic acid, sebacic acid, maleic acid, fumaric acid and the like.

Examples of 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 or different alkyl groups.

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

Lactams As the lactams, those having 4 to 7 ring-forming atoms such as β-propiolactam, γ-butyrolactam, ε-caprolactam, and δ-valerolactam are preferable.
The lactams may have a substituent, and as the substituent, alkyl, particularly one having 5 to 20 carbon atoms, preferably 7 to 16 carbon atoms is preferable, and examples thereof include dodecyl, heptyl, octyl and hexadecyl. To be done. The substituent is preferably substituted at the N position of the lactam ring.

Examples of preferred lactams include 1-dodecylazacycloheptanone and 1-dodecylpyrrolidone.

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

Regarding the general formula (III), the alkyl having 5 or more carbon atoms represented by Rc may be saturated, unsaturated, chain-like or cyclic. The preferred carbon number of such alkyl is 6-24.
The saturated alkyl group preferably has 5 to 20 carbon atoms, and examples thereof include n-pentyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tetradecyl, n-hexadecyl, n-octadecyl, Linear ones such as n-eicosyl, 2-methylhexyl, 2-ethylhexyl, 3,7-dimethyloctyl, 2-hexyldecyl, 2-octyldodecyl, 2,4,4-trimethyl1-
Examples include branched ones such as pentyl and 1-methyloctyl. The unsaturated alkyl preferably has 6 to 24 carbon atoms, and examples thereof include cis-3-hexenyl, oleyl and linoleyl. Total carbon number of cyclic alkyl is 6-12
Is particularly preferable, for example, 2-cyclohexylethyl,
Examples thereof include ring-containing alkyl such as cycloheptyl, cyclohexylmethyl, cyclooctyl, 4-cyclohexylbutyl, 3-cyclopentylpropyl, 5-methyl-2-isopropylcyclohexyl, and the simple number forming the cyclic portion is 6 to 8, that is, A 6-8 membered ring is preferred.

Monoester of alkylene glycol and aliphatic carboxylic acid As the alkylene group in the alkylene glycol used in the present invention, ethylene or propylene is preferable, and the aliphatic carboxylic acid has 6 to 22 carbon atoms, preferably 10 to 18 carbon atoms. 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.

Examples of preferable monoesters of alkylene glycol and aliphatic carboxylic acid include propylene glycol monolaurate and propylene glycol monomyristate.

1-Alkyl-2-pyrrolidone-5-carboxylic acid aliphatic hydrocarbon ester (1-alkyl PCA ester) The aliphatic hydrocarbon ester portion of the 1-alkyl PCA ester preferably has about 1 to 24 carbon atoms. . Examples of the ester include alkyl ester and unsaturated hydrocarbon ester. The alkyl in the alkyl ester may be cyclic, that is, cycloalkyl, or may be linear (either linear or branched). 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. The unsaturated hydrocarbon ester preferably has 6 to 24 carbon atoms, which may be chain-like or cyclic. The unsaturated group contained therein is preferably a double bond, and the number thereof is preferably 1 or 2.

The alkyl group in the 1-position alkyl moiety is preferably one having 1 to 5 carbon atoms such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, t-butyl, iso-amyl, n-amyl and the like. .

Specifically, as the chain alkyl ester, 1-alkylpyrrolidonecarboxylic acid methyl ester, 1-alkylpyrrolidonecarboxylic acid ethyl ester, 1-alkylpyrrolidonecarboxylic acid n-propyl ester, 1-alkylpyrrolidonecarboxylic acid n-butyl ester Ester, 1-alkylpyrrolidonecarboxylic acid n-heptyl ester, 1
-Alkylpyrrolidonecarboxylic acid n-octyl ester, 1-alkylpyrrolidonecarboxylic acid n-nonyl ester, 1-alkylpyrrolidonecarboxylic acid n-decyl ester, 1-alkylpyrrolidonecarboxylic acid n-undecyl ester, 1-alkylpyrrolidonecarboxylic acid n-
Dodecyl ester, 1-alkylpyrrolidonecarboxylic acid n-tridecyl ester, 1-alkylpyrrolidonecarboxylic acid n-tetradecyl ester, 1-alkylpyrrolidonecarboxylic acid n-hexadecyl ester, 1-alkylpyrrolidonecarboxylic acid n-octadecyl ester, 1
-Alkylpyrrolidonecarboxylic acid n-eicosyl ester, 1-alkylpyrrolidonecarboxylic acid iso-propyl ester, 1-alkylpyrrolidonecarboxylic acid 2-methylhexyl ester, 1-alkylpyrrolidonecarboxylic acid 2-ethylhexyl ester, 1-alkylpyrrolidonecarboxylic acid Acid 3,7-dimethyloctyl ester, 1-
Alkylpyrrolidone carboxylic acid 2-hexyldecyl ester, 1-alkylpyrrolidone carboxylic acid 2-octyldodecyl ester, 1-alkylpyrrolidone carboxylic acid
Examples thereof include linear and branched ones such as 2,4,4-trimethyl 1-pentane ester and 1-alkylpyrrolidone carboxylic acid methyl octyl ester. Alkyl in 1-alkyl in the above compound is methyl, ethyl,
Examples include n-propyl, iso-propyl, n-butyl, n-amyl, iso-amyl and the like.

As the cyclic alkyl ester, 1-alkylpyrrolidonecarboxylic acid 2-cyclohexylethyl ester, 1-
Alkylpyrrolidonecarboxylic acid cycloheptyl ester, 1-alkylpyrrolidonecarboxylic acid cyclohexylmethyl ester, 1-alkylpyrrolidonecarboxylic acid cyclooctyl ester, 1-alkylpyrrolidonecarboxylic acid 4-cyclohexylbutyl ester, 1-alkylpyrrolidonecarboxylic acid 3-cyclopentylpropyl ester Ester, 1-alkylpyrrolidonecarboxylic acid 5-methyl-
2-Isopropylcyclohexyl ester Ado is mentioned. Alkyl in 1-alkyl in the above compounds is methyl, ethyl, n-propyl, iso-propyl, n-butyl, n-amyl, iso-amyl and the like.

As the unsaturated hydrocarbon ester, 1-alkylpyrrolidonecarboxylic acid-cis-3-hexenyl ester, 1-
Alkylpyrrolidone carboxylic acid-oleyl ester, 1
-Alkylpyrrolidone carboxylic acid linoleyl ester and the like can be mentioned. Alkyl in 1-alkyl in the above compounds is methyl, ethyl, n-propyl, iso-
Propyl, n-butyl, n-amyl, iso-amyl and the like.

Examples of the unsaturated hydrocarbon ester further include esters derived from terpene alcohol, and specific examples thereof include 1-alkylpyrrolidonecarboxylic acid geranyl ester and the like, and the carbon number of the terpene alcohol in that case is 10 to 20. Is preferred. Alkyl in 1-alkyl in the above compound is methyl, ethyl,
Examples include n-propyl, iso-propyl, n-butyl, n-amyl, iso-amyl and the like.

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, which may be saturated or unsaturated, for example, a fatty acid is preferable, and as the aliphatic acid, Examples include capric acid, lauric acid, myristic acid, oleic acid and the like.

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

Proline ester or N-alkyl proline ester The compound used in the present invention has a general formula (In the formula, Rd represents a hydrogen atom or an aliphatic hydrocarbon group, and
Represents an aliphatic hydrocarbon residue, and the total carbon number of Rd and Re is 20 or less). [Hereinafter, the compound is referred to as proline ester (IV)
Also called].

Regarding the general formula (IV), the aliphatic hydrocarbon group represented by Rd and Re may be saturated or unsaturated, or may be linear, branched or cyclic. The number of carbon atoms of the aliphatic hydrocarbon residue is preferably about 1 to 20, 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 therein is preferably a double bond, and the number of unsaturated bonds is 1-2.
It is desirable to be individual. Further, in the case of a cyclic group, those having 5 to 12 carbon atoms are preferable, and the number of rings is 1,
It is preferably a 5- to 7-membered ring.

Examples of the aliphatic hydrocarbon group for Rd include methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-
Lower alkyl having 1 to 5 carbon atoms such as butyl, tert-butyl, n-amyl and iso-amyl is preferable.

Examples of the aliphatic hydrocarbon residue for Re include n
-Hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-
Tridecyl, n-tetradecyl, n-hexadecyl, n
-Saturated chain having 6 to 18 carbon atoms such as octadecyl, 2-methylhexyl, 2-ethylhexyl, 3,7-dimethyloctyl, 2-hexyldecyl, 2-cyclohexylethyl, cycloheptyl, cyclohexylmethyl,
Saturated cyclic ones having 6 to 12 carbon atoms such as 4-cyclohexylbutyl and 3-cyclopentylpropyl, cis-3-
Unsaturated ones having 6 to 18 carbon atoms such as hexenyl, 2-decenyl, oleyl, menthyl and geranyl are preferable.

Specific examples of the proline ester (IV) include, for example, N
-Methylproline lauryl ester, proline heptyl ester, N-ethylproline tetradecyl ester and the like can be mentioned.

The proline ester (IV) may be used as its salt, and the salt is not particularly limited as long as it is pharmacologically acceptable, and examples thereof include organic acids (eg citric acid, tartaric acid, succinic acid, maleic acid). Acid, fumaric acid, etc.), inorganic acids (for example, mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.) and the like.

Cineol The blending amount of minoxidil in the hair nourishing composition of the present invention is
It may be an amount sufficient to exert a hair nourishing effect, and it may vary depending on the patient's symptoms, dosage form, etc., and may be appropriately selected according to the conditions. For example, it is about 0.1 to 10% by weight.

The amount of the absorption-promoting aid to be blended may be sufficient to promote percutaneous absorption of minoxidil, and it varies depending on the dosage form, etc., but usually 0.01 to 20% by weight relative to the total amount of the formulation, especially It is preferably about 0.2 to 10% by weight.

The skin application area of the composition of the present invention varies depending on the patient, and is not necessarily limited to the above-mentioned amount.

The composition of the present invention contains an ointment, a plaster, a lotion, an adhesive tape, an impregnating agent, a gel by adding known ingredients (eg, bases, excipients, stabilizers, coloring agents) which are pharmaceutically acceptable. As an agent or the like, it is used in the form of hair lotion, hair tonic, hair cream, shampoo or applied to the inner wall of a wig.

[Action]

The composition of the present invention has an action of promoting absorption of minoxidil by the absorption-promoting aid blended therein, so that the composition of the present invention enhances the transdermal absorbability of minoxidil, and thus, minoxidil is absorbed in a short time. It is absorbed and can be commercialized as a lotion type, and a sufficient amount of minoxidil administration gives a sufficient hair nourishing effect.
It is highly safe.

〔Example〕

Examples 1-20 The basic formulation is ethanol (95 °) 44.5%, purified water 44.5%,
A formulation was prepared in which minoxidil was 1% and the accelerators shown in 1 to 20 below were added 10% each.

Table 1 1. Linalyl alcohol 2. Lauryl alcohol 3. n-Nonane 4. n-Dodecane 5. Dibromododecane 6. Isopropyl myristate 7. Methyl oleate 8. N-Dodecylmorpholine 9. N-Nonylmorpholine 10. Methyl laurate 11. Diisopropyl adipate 12.1-Dodecylazacycloheptanone 13.1-Dodecylpyrrolidone 14. Nicotinic acid lauryl ester 15. Propylene glycol monolaurate 16. N-Methylpyrrolidone carboxylic acid lauryl 17. Cineol 18. Glycerin monolaurate 19. N-Methylproline lauryl ester 20. Proline lauryl ester Comparative Example Among the components of Examples 1 to 20, ethanol 49.5% and purified water 49.5% were mixed, and minoxidil 1% was mixed and dissolved, except for the transdermal absorption enhancer. I used one.

Experimental Example Rat abdominal skin was excised, and the portion corresponding to the surface of the skin was in contact with the compositions of Examples 1 to 20 and Comparative Example, while the portion corresponding to the back side of the skin was in contact with physiological saline. It was attached to a glass permeation cell and minoxidil permeated into physiological saline was quantified by high performance liquid chromatography. This test was conducted in a sealed container.
The obtained results were obtained as acceleration ratio: A / BA: skin permeation amount of drug in Example formulation B: skin permeation amount of drug in Comparative Example formulation, and the results are shown in Table 1.

[Effect] A hair nourishing composition obtained by adding a percutaneous absorption enhancer to minoxidil according to the present invention is more effective than that without the percutaneous absorption enhancer.
It exhibits excellent skin permeation of 10.3 to 35.0 times, and thus, minoxidil is absorbed in a short time and a sufficient hair-growth effect is exhibited by administration of a small amount of minoxidil.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Shigeyuki Watanabe 1-2-1, Shimohozumi, Ibaraki City, Osaka Prefecture Nitto Denki Kogyo Co., Ltd. (56) Reference JP-A-62-192313 (JP, A) JP 62-69 (JP, A)

Claims (1)

[Claims] 1. A hair nourishing composition comprising minoxidil and at least one transdermal absorption promoting auxiliary selected from the following: Alcohol having 7 to 15 carbon atoms, aliphatic hydrocarbon having 5 to 30 carbon atoms which may be substituted with halogen, total carbon number
Alkyl esters of 13-24 aliphatic carboxylic acids, N-
Alkyl morpholine, alcohol diester having 4 to 10 carbon atoms and dicarboxylic acid having 1 to 3 carbon atoms, lactams,
Nicotinic acid ester, monoester of alkylene glycol and aliphatic carboxylic acid, 1-alkyl-2-
An aliphatic hydrocarbon ester of pyrrolidone-5-carboxylic acid, a carboxylic acid monoester of glycerin having 10 to 18 carbon atoms, a proline ester or an N-alkylproline ester, and cineol.