JPH08295616A - Hair tonic - Google Patents

Abstract

PURPOSE: To obtain a hair tonic comprising a partially new carnitine derivative as an active ingredient, useful as a preventive and a therapeutic agent for male pattern alopecia, senile slight hair disease, telogen effluvium or white hair. CONSTITUTION: This hair tonic comprises a carnitine derivative of formula I (R<1> to R<3> are each a 1-6C alkyl; R<4> is a 3-31C aliphatic acyl; R<5> is a 3-31C alkyl or a 3-31C alkenyl; X<-> is a pharmacologically permissible anion) as an active ingredient. For example, new (R)-(2-pentadecanoyloxy-3- undecyloxycarbonylpropyl)trimethylammonium chloride, etc., may be cited as the compound of formula I. The compound of formula I, for example, is obtained by condensing a compound of formula II with a compound of the formula R<5> Y (Y is a halogen). The compound of formula II is obtained by reacting a carnitine derivative of formula III with a carboxylic acid compound of the formula R<4> OH.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a hair-growing agent and a carnitine derivative having a hair-growing action.

[0002]

2. Description of the Related Art As energy required for hair growth, ATP, which is produced by the metabolism of glucose through glycolysis and TCA cycle, is usually used. However, in androgenetic alopecia, phosphofructokinase (PFKase), which is one of the enzymes that catalyze glycolysis, is inhibited by male hormones, and energy supply is suppressed.

Conventionally, a hair nourishing agent containing pentadecanoic acid monoglyceride, pelargonic acid ester of carnitine [(3-carboxy-2-hydroxypropyltrimethylammonium hydroxide, inner salt] or heptadecanoic acid ester as an active ingredient is known (special feature: Kosho 63-4
No. 1363, Japanese Examined Patent Publication No. 6-45533). Further, a hair nourishing agent containing a straight-chain aliphatic monohydric alcohol having an odd number of carbon atoms having 5 to 25 carbon atoms as an active ingredient is known (Japanese Patent Publication No. 63-41364). Furthermore, JP-A-1-199990
No. 5 describes that γ-trialkylammonium-β-hydroxybutyrate chloride (carnitine hydrochloride) has a hair-feeding effect.

On the other hand, JP-A-5-339218 discloses undecanoyl-L-carnitine undecyl ester chloride [(R)-(2-undecanoyloxy-3-undecyloxycarbonylpropyl) trimethylammonium chloride] and the like. Carnitine derivatives are disclosed. Although these compounds are described as having an antibacterial effect, there is no description about the hair-growth effect. Further, JP-A-5-339219 describes that the same compounds as disclosed in JP-A-5-339218 have an antifungal action, but there is no description about hair-growth action at all. Further, JP-A-55-167262 describes that propionyl carnitine isopropyl ester and isobutyryl carnitine isobutyl ester are useful as therapeutic agents for myocardial low contraction, but there is no description about hair-growth action.

[0005]

DISCLOSURE OF THE INVENTION The present invention provides an excellent hair-growing agent containing a carnitine derivative as an active ingredient.

[0006]

The present invention has the general formula [I]

[0007]

Embedded image

[Wherein R ^{1 to} R ³ are alkyl groups having 1 to 6 carbon atoms, R ⁴ is a substituted or unsubstituted aliphatic acyl group having 3 to 31 carbon atoms, and R ⁵ is a substituted or unsubstituted carbon group] An alkyl group of 3 to 31 or a substituted or unsubstituted alkenyl group of 3 to 31 carbon atoms, X ⁻ represents a pharmacologically acceptable acid anion. ] It is related with the hair growth agent which uses the carnitine derivative shown by these as an active ingredient.

The carnitine derivative [I] according to the present invention is
Compared with conventional hair restorers, it has a superior hair restorer effect and is useful as a hair restorer.

Specific examples of the carnitine derivative [I] which is the active ingredient of the present invention include R ^{1 to} R ^{3 which} are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl and 3-. A methylbutyl group, a hexyl group, an isohexyl group or another alkyl group having 1 to 6 carbon atoms, wherein the aliphatic acyl group having 3 to 31 carbon atoms in R ⁴ is a propionyl group, butyryl group, isobutyryl group, crotonoyl group, methacryloyl group, valeryl. Group, isovaleryl group, pivaloyl group, hexanoyl group, 4-methylvaleryl group, sorbinoyl group, heptanoyl group, octanoyl group, 2-propylvaleryl group, nonanoyl group, decanoyl group, undecanoyl group, 10-undecenoyl group,
Dodecanoyl group, tridecanoyl group, tetradecanoyl group, pentadecanoyl group, hexadecanoyl group, heptadecanoyl group, octadecanoyl group, oleoyl group, eridoyl group, linoleoyl group, linolenoyl group, nonadecanoyl group, 2,6,10 , 14-Tetramethylpentadecanoyl group, icosanoyl group, 3,7,11,15
-Tetramethylhexadecanoyl group, arachidoyl group,
Henicosanoyl group, docosanoyl group, tricosanoyl group, tetracosanoyl group, pentacosanoyl group, hexacosanoyl group, heptacosanoyl group, octacosanoyl group, nonacosanoyl group, triacontanoyl group, or hentriacontanoyl group and the like, having 3 carbon atoms in R ⁵ .
~ 31 alkyl groups are propyl group, isopropyl group, butyl group, isobutyl group, 1-methylpropyl group, 1,1
-Dimethylethyl group, pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1,1
-Dimethylpropyl group, 1,2-dimethylpropyl group,
2,2-dimethylpropyl group, 1-ethylpropyl group,
2-ethylpropyl group, hexyl group, isohexyl group,
1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 1-ethylbutyl group, 2-ethylbutyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group Group, 2,2-dimethylbutyl group, 2,3-dimethylbutyl group, 3,3-dimethylbutyl group, 1-ethyl-1-methylpropyl group, 1-
Ethyl-2-methylpropyl group, 2-ethyl-1-methylpropyl group, 2-ethyl-2-methylpropyl group, 1
-Methyl-2-ethylpropyl group, 1,1,2-trimethylpropyl group, 1,2,2-trimethylpropyl group,
Heptyl group, octyl group, 2-propylpentyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group, nonadecyl group, icosyl group, henicosyl group. A docosyl group, a tricosyl group, a tetracosyl group, a pentacosyl group, a hexacosyl group, a heptacosyl group, an octacosyl group, a nonacosyl group, a triacontyl group or a hentriacontyl group, and the alkenyl group having 3 to 31 carbon atoms in R ⁵ is 2-
Propenyl group, 1-methylethynyl group, 10-undecenyl group, 14-pentadecenyl group, 3,7,11,15
-Tetramethyl-2-hexadecenyl group, 20-henicosenyl group, 30-hentriacontenyl group and the like,
R ³ is an aliphatic acyl group having 3 to 31 carbon atoms or R ⁵
An alkyl group having 3 to 31 carbon atoms or 3 carbon atoms
To 31 are hydroxyl groups, or methoxycarbonyl group, ethoxycarbonyl group, propyloxycarbonyl group, isopropyloxycarbonyl group, butyloxycarbonyl group, isobutyloxycarbonyl group, pentyloxycarbonyl group, 3-methylbutyl group. Examples thereof include compounds having an alkoxycarbonyl group having 2 to 7 carbon atoms such as an oxycarbonyl group, a hexyloxycarbonyl group, an isohexyloxycarbonyl group, a heptyloxycarbonyl group, and 5-methylhexyloxycarbonyl.

Examples of the preferred compound [I] include R ^{1 to} R ³
Is a compound having 1 to 4 carbon atoms, R ⁴ is an aliphatic acyl group having 3 to 18 carbon atoms, and R ⁵ is an alkyl group or alkenyl group having 3 to 21 carbon atoms, and more specifically,
For example, R ⁴ is a propionyl group, isobutyryl group, valeryl group, hexanoyl group, 4-methylvaleryl group, heptanoyl group, octanoyl group, 2-propylvaleryl group, nonanoyl group, undecanoyl group, 10-undecenoyl group, dodecanoyl group, tridecanoyl group. Group, tetradecanoyl group, pentadecanoyl group, hexadecanoyl group, heptadecanoyl group, linoleoyl group or 3-ethoxycarbonylpropionyl group, R ⁵ is propyl group, isobutyl group, pentyl group, 1-ethylpropyl group, 1-
Methylbutyl group, 2-methylbutyl group, isohexyl group, heptyl group, 2-propylpentyl group, nonyl group,
Decyl group, undecyl group, dodecyl group, tridecyl group,
Tetradecyl group, pentadecyl group, henicosyl group, 1
The compound is a 0-undecenyl group, a 3-ethoxycarbonylpropionyl group or a 12-hydroxydodecyl group. Among these, especially R ⁴ is propionyl group, isobutyryl group, valeryl group, hexanoyl group, 4-methylvaleryl group, heptanoyl group, 2-propylvaleryl group, nonanoyl group, undecanoyl group, 10-undecenoyl group, tridecanoyl group, tetra Decanoyl group, pentadecanoyl group, hexadecanoyl group, heptadecanoyl group or linoleoyl group, R ⁵ is propyl group, pentyl group, 2-methylbutyl group, isohexyl group, heptyl group, nonyl group, decyl group, undecyl group, dodecyl Base,
A compound which is a tridecyl group, a tetradecyl group, a pentadecyl group, a henicosyl group or a 10-undecenyl group is preferable.

Further preferred examples of the compound [I] are R ¹
~ R ³ is an alkyl group having 1 to ⁴ carbon atoms, and R ⁴ is 3 to ⁴ carbon atoms.
A compound having 15 aliphatic acyl groups and R ⁵ being an alkyl group having 3 to 15 carbon atoms, and more specifically, for example, R 5
⁴ is a propionyl group, isobutyryl group, valeryl group, 4
-Methylvaleryl group, hexanoyl group, heptanoyl group, undecanoyl group, 10-undecenoyl group, tridecanoyl group or pentadecanoyl group, R ⁵ is propyl group, pentyl group, 2-methylbutyl group, heptyl group, nonyl group, undecyl group, dodecyl A compound which is a group, a tridecyl group, a tetradecyl group or a pentadecyl group.

Another preferred compound is the sum (a +) of the carbon number (= a) of the aliphatic acyl group in R ⁴ and the carbon number (= b) of the alkyl group or alkenyl group in R ⁵ .
The b) may be 6 to 34, especially 14 to 26. As a specific example of the combination of a and b, for example, (1) where a + b = 6, (a, b) =
(3, 3), (2) a + b = 8,
(A, b) = (5, 3), (3) a + b = 12
The following are (a, b) = (5, 7), (4) a
+ B = 14 is (a, b) = (3,11) or (11,3), (5) a + b = 15 is
Those in which (a, b) = (4,11), (6) a + b = 1
6 has (a, b) = (3,13), (5,1)
1), (7,9), (11,5) or (13,3), (7) a + b = 17, (a, b) =
(4,13), (5,12) or (6,11), (8) a + b = 18, (a, b) = (3,1
5), (4,14), (5,13), (6,12),
(7,11), (9,9), (11,7), (13,
5) or (15,3), (9) a + b = 19, (a, b) = (4,15), (6,13),
(8,11), (11,8), (13,6), (15,
4) or (16,3), (10) a + b = 20, (a, b) = (5,15), (7,13),
(9,11), (11,9) or (13,7), (11) a + b = 21, (a, b) = (8,1)
3), (16,5) or (18,3), (12)
For a + b = 22, (a, b) = (7,15),
What is (11,11) or (13,9), (13) a +
For b = 23, (a, b) = (8,15), and for (14) a + b = 25, (a, b) = (13,
12), (14,11) or (16,9),
(15) a + b = 26, (a, b) = (13,1)
3) or (15, 11), (16) a + b = 27
Is (a, b) = (16,11), (1
7) For a + b = 28, (a, b) = (15,1)
3), (17,11) or (16,12),
(18) For a + b = 30, (a, b) = (15,1)
5) and (19) a + b = 34 are (a,
b) = (13, 21) can be mentioned.

Examples of other preferred compounds [I] include R ¹ to
R ³ is an alkyl group having 1 to 6 carbon atoms, R ⁴ is ⁴ to 3 carbon atoms
1 is a compound in which R ⁵ is an aliphatic acyl group and R ⁵ is an alkyl group having 11 to 31 carbon atoms.

Further, another preferred example of the compound [I] is that the aliphatic acyl group in R ⁴ or the alkyl group in R ⁵ is a branched chain C 4-15 aliphatic acyl group or alkyl group. Among them, compounds having a branched chain structure by branching a methyl group are preferable. Further, the position where the methyl group is branched is preferably an even position of the main carbon chain, and particularly preferably such an even position is a position next to the carbon atom at the end of the main carbon chain.

In the carnitine derivative [I] as the active ingredient of the present invention, the aliphatic acyl group for R ⁴ has an even carbon chain length, an odd carbon chain length, or a straight chain type. Examples thereof include branched type, saturated type, and unsaturated type. Examples of the alkyl group or alkenyl group for R ⁵ include those having an even carbon chain length, those having an odd carbon chain length, and those having a straight chain type and a branched chain type.

The most preferred examples of the compound [I] are (1) R
^{1 to} R ³ are methyl groups, R ⁴ is a pentadecanoyl group, R ⁵
Is an undecyl group; (2) R ^{1 to} R ³ are methyl groups, and R ⁴ is 4
-Methylvaleryl group, R ⁵ is an undecyl group; (3) R ¹ ~
R ³ is a methyl group, R ⁴ is a valeryl group, R ⁵ is a tridecyl group; (4) R ^{1 to} R ³ are methyl groups, R ⁴ is a propionyl group, R ⁵ is an undecyl group; (5) R ^{1 to} R ³ Is a methyl group,
R ⁴ is a tridecanoyl group, R ⁵ is a pentyl group; (6) R ¹
To R ³ are methyl groups, R ⁴ is a heptanoyl group, R ⁵ is a nonyl group; (7) R ^{1 to} R ³ are methyl groups, R ⁴ is a heptanoyl group, R ⁵ is a tridecyl group; (8) R ^{1 to} R ³ is a methyl group,
R ⁴ is an undecanoyl group, R ⁵ is a pentyl group; (9) R ¹
To R ³ are methyl groups, R ⁴ is valeryl group, R ⁵ is undecyl group; (10) R ^{1 to} R ³ are methyl groups, R ⁴ is undecanoyl group, R ⁵ is heptyl group; (11) R ^{1 to} R ³ is a methyl group,
R ⁴ is tridecanoyl group, R ⁵ is heptyl group; (12) R ¹
To R ³ are methyl groups, R ⁴ is an isobutyryl group, R ⁵ is a tridecyl group; (13) R ^{1 to} R ³ are methyl groups, R ⁴ is a propionyl group, R ⁵ is a tridecyl group; (14) R ^{1 to} R ³ is a methyl group, R ⁴ is a 4-methylvaleryl group, R ⁵ is a dodecyl group;
(15) R ^{1 to} R ³ are methyl groups, R ⁴ is a 4-methylvaleryl group, R ⁵ is a tridecyl group; (16) R ^{1 to} R ³ are methyl groups,
R ⁴ is an isobutyryl group, R ⁵ is a tetradecyl group; (17) R
^{1 to} R ³ are methyl groups, R ⁴ is valeryl group, R ⁵ is pentadecyl group; (18) R ^{1 to} R ³ are methyl groups, R ⁴ is propionyl group, R ⁵ is pentadecyl group; (19) R ¹ to R ³ is a methyl group, R ⁴ is a hexanoyl group, and R ⁵ is an undecyl group; among these, compounds other than (2) and (7) are novel compounds.

The carnitine derivative [I] according to the present invention is
Carnitine (3-carboxy-2-hydroxypropyltrimethylammonium hydroxide, inner salt) 2
Asymmetric carbon atom at position and R ¹ , R ² , R ³ , R ⁴ or R ⁵
Both optical isomers and mixtures thereof based on the asymmetric carbon atom present in Among these, those in which the asymmetric carbon atom at the 2-position of carnitine has the R configuration are particularly preferable in terms of drug efficacy.

In the present invention, the alkyl group having 1 to 6 carbon atoms (R ^{1 to} R ³ ) has 1 to 4 carbon atoms, for example, methyl group, ethyl group, propyl group, isopropyl group,
A butyl group, an isobutyl group and the like are more preferable, and a methyl group is particularly preferable. The alkoxycarbonyl group having 2 to 7 carbon atoms, which is a substituent of the aliphatic acyl group for R ⁴ or the alkyl group or alkenyl group for R ⁵ , is more preferably one having 2 to 5 carbon atoms, and particularly preferably an ethoxycarbonyl group. . The pharmacologically acceptable acid anion (X ⁻ ) is, for example, chloride,
Acetate, citrate, nicotinate, nitrate,
Examples thereof include sulfonate and salicylate, and among these, chloride, nicotinate, nitrate and sulfonate are preferable, and chloride, nicotinate and nitrate are particularly preferable.

The hair restorer of the present invention can be used in various forms such as a hair nourishing agent, a hair tonic, a hair lotion, a hair cream, a shampoo, and a conditioner according to a conventional method. In addition to the carnitine derivative which is the active ingredient of the present invention, these hair-growing agents may be blended with the ones usually used in the production thereof. For example, distilled water as a base,
Alcohols, polyhydric alcohols, surfactants, oils and fats, etc. are mixed, and further, vitamins, hormones, vasodilators, amino acids, anti-inflammatory agents, skin function enhancers, keratolytic agents, etc. What has been blended with a known hair restorer can be blended at the same time.

The blending amount of the active ingredient of the present invention is not particularly limited, and may be appropriately blended depending on the amount and type of other blending agents such as a base, but usually 0.1 to 2 of the total blending amount. About wt% is appropriate.

The carnitine derivative [I] of the present invention has, for example, the general formula [II]

[0023]

[Chemical 4]

(Wherein the symbols have the same meanings as described above), a compound represented by the general formula [III]

[0025]

Embedded image

(In the formula, R ⁵ has the same meaning as described above, and Y 5
Represents a halogen atom. ) It can manufacture by condensing with the compound shown by.

The carnitine derivative of the present invention [I]
Is, for example, a compound represented by the general formula [II]

[0028]

[Chemical 6]

(Wherein the symbols have the same meanings as described above) or a reactive derivative at the carboxyl group thereof is represented by the general formula [IV]

[0030]

[Chemical 7]

(Wherein the symbols have the same meanings as described above) and can be produced by condensation.

Condensation reaction of compound [II] with compound [III] and reactive derivative of compound [II] with compound [I]
V] is condensed in a suitable solvent (eg, dimethylformamide, tetrahydrofuran, methylene chloride, ethyl acetate, acetonitrile, etc.) with a deoxidizing agent (eg, alkali metal hydroxide, alkali metal carbonate, alkali metal hydrogen carbonate, N 2 , N-dialkylaniline, pyridine, N-alkylmorpholine, tri-lower alkylamine, etc.) can be appropriately performed in the presence or absence. The reaction is 0 ° C
It suitably proceeds at a temperature of -60 ° C.

The condensation reaction of the compound [II] and the compound [IV] is carried out in the same solvent as used in the above condensation reaction, in a condensing agent (for example, N, N'-dicyclohexylcarbodiimide, N-cyclohexyl-N'-morpholino). Carbodiimide, N-ethyl-N '-(3-dimethylaminopropyl) carbodiimide and the like) can be appropriately performed in the presence or absence. The reaction suitably proceeds at a temperature of -30 ° C to 30 ° C.

As the reactive derivative of the compound [II],
Corresponding acid halides, mixed acid anhydrides, active esters and the like can be used.

The carnitine derivative [I] of the present invention thus obtained is optionally reacted with, for example, a pharmacologically acceptable alkali metal salt of an acid (eg, sodium salt, potassium salt, etc.) to give X ⁻ . It can be converted to the anion of other pharmacologically acceptable acids.

The starting compound [II] has the general formula [V]

[0037]

Embedded image

The carnitine derivative represented by the formula [VI]

[0039]

[Chemical 9]

It can be produced by reacting with a carboxylic acid compound represented by the formula (wherein the symbols have the same meanings as described above) by a conventional method, for example, in the same manner as the above condensation reaction.

[0041]

[Action]

Experimental Example 1 (hair-growth action of shaved mice) (Method) The backs of 10 male C3H / HeN mice (6 weeks old) per group were shaved with an electric clipper and then a safety razor 3 days before the start of application of the sample. A 2% (W / V) or 0.5% (W / V) ethanol solution of the sample or 0.1 ml of ethanol (control group) is applied to the shaved site once a day for 5 days a week for 30 days from 7 weeks of age. did. The hair-growth action was evaluated by scoring the degree of hair growth into the following 6 levels.

No hair growth is observed: 0 Hair growth occurs in less than 25% of the shaved area: 1 Hair growth occurs in 25% or more and less than 50% of the shaved area: 2 Hair in the shaved area 50% or more and less than 75% of hair growth: 3 Hair growth is 75% or more and less than 100% of shaving area Hair growth: 4 Hair growth is 100% of hair shaving area: 5 (Result) It is as described in Tables 1 and 2 below. Table 1 shows the results obtained using a 2% (W / V) ethanol solution of the sample, and Table 2 shows 0.5% of the sample.
The result obtained using the (W / V) ethanol solution is shown.

[0043]

[Table 1]

[0044]

[Table 2]

[0045]

[Table 3]

[0046]

[Table 4]

[0047]

【Example】

Example 1 (R)-(3-Carboxy-2-tridecanoyloxypropyl) trimethylammonium chloride (1.5
g; 3.81 mmol) dimethylformamide 30 m
triethylamine (0.53 ml; 3.81)
mmol), 1-bromotridecane (5.0 g; 19.
0 mmol) in order, and under argon atmosphere, 50-6
Stir at 0 ° C. for 23 hours. The reaction solvent was evaporated under reduced pressure, 20 ml of diethyl ether was added to the residue, the mixture was stirred at room temperature, the insoluble material was collected by filtration, washed with diethyl ether and dried to give crude (R)-(2-tridecanoyloxy- 2.5 g of 3-tridecyloxycarbonylpropyl) trimethylammonium bromide are obtained as a colorless solid. 2.5g of this product
50 ml of water is added to the mixture, and the mixture is stirred at room temperature for 1 hour, and then extracted with tetrahydrofuran-ethyl acetate (1: 1). 100 ml of saturated saline and 30 ml of water were added to the extracted organic layer,
After stirring for 18 hours at room temperature, the organic layer is separated. The organic layer was washed with saturated brine and water, the solvent was evaporated under reduced pressure, azeotroped with ethyl acetate, and dried under reduced pressure at room temperature to give 1.75 g of the crude target product.
Get. This product was recrystallized from ethyl acetate (R)-(2-
Tridecanoyloxy-3-tridecyloxycarbonylpropyl) trimethylammonium chloride 1.58
g are obtained as colorless crystals.

M. p. 146-147 ° C IR (Nujol) cm ^-1 : 1735, 1725 NMR (CDCl ₃ ) δ: 0.88 (6H, t, J =
6.8 Hz), 1.26 (38H, brs), 1.55
-1.65 (4H, m), 2.31-2.36 (2H,
m), 2.80 (1H, dd, J = 17, 5.9H)
z), 2.85 (1H, dd, J = 17, 6.8H
z), 3.52 (9H, s), 4.01-4.13 (3
H, m), 4.32 (1H, brd), 5.64-5.
71 (1H, m).

Example 2 (R)-(3-Carboxy-2-pentadecanoyloxypropyl) trimethylammonium chloride was treated as in Example 1 to give (R)-(2-pentadecanoyloxy-3). -Tridecyloxycarbonylpropyl) trimethylammonium chloride is obtained.

M. p. 153-154 ° C IR (Nujol) cm ^-1 : 1760, 1740, 17
30 NMR (CDCl ₃ ) δ: 0.88 (6H, t, J =
6.8Hz), 1.26 (42H, brs), 1.55
-1.65 (4H, m), 2.30-2.36 (2H,
m), 2.80 (1H, dd, J = 17, 6.0H
z), 2.85 (1H, dd, J = 17, 6.8H
z), 3.53 (9H, s), 4.03-4.12 (3
H, m), 4.34 (brd), 5.64-5.71.
(1H, m).

Example 3 (R)-(3-Carboxy-2-pentadecanoyloxypropyl) trimethylammonium chloride (2 g;
Oxalyl chloride (1.41 g; 11.1 mmol) was added dropwise to a suspension (4.74 mmol) of methylene chloride in 10 ml under ice-cooling, and the mixture was stirred at room temperature for 2.5 hours. The reaction solvent was evaporated under reduced pressure, and the residue was azeotropically distilled with toluene (15 ml × 2) to obtain crude acid chloride as a colorless solid. Add 10 ml of methylene chloride to the total amount of this product, cool with ice under an argon atmosphere,
1-Undecanol (1.49 ml; 7.2 mmol)
Is dripped. The reaction solution is stirred with ice cooling for 2.5 hours and at room temperature for 30 minutes, and then the solvent is distilled off. Diethyl ether 6 in the residue
0 ml was added, the mixture was stirred at room temperature for 15 minutes, the insoluble matter was collected by filtration, washed with diethyl ether, and dried to obtain 2.62 g of the crude target product as a colorless solid. 50 ml of water was added to 2.62 g of the crude product, and the mixture was stirred at room temperature for 1 hour, extracted with tetrahydrofuran-ethyl acetate (1: 1), the extract was evaporated under reduced pressure, and the solid residue was subjected to azeotropic distillation with ethyl acetate. Recrystallization is performed to obtain 2.0 g of (R)-(2-pentadecanoyloxy-3-undecyloxycarbonylpropyl) trimethylammonium chloride as colorless crystals.

M. p. : 152-153 ° C IR (Nujol) cm ^-1 : 1760, 1740, 17
30 NMR (CDCl ₃ ) δ: 0.88 (6H, t, J =
6.7 Hz), 1.26 (38H, brs), 1.54
-1.66 (4H, m), 2.30-2.36 (2H,
m), 2.80 (1H, dd, J = 17, 5.9H)
z), 2.85 (1H, dd, J = 17, 6.7H
z), 3.53 (9H, s), 4.03-4.11 (3
H, m), 4.34 (brd), 5.64-5.71.
(1H, m).

Examples 4 to 5 The corresponding starting compounds are treated in the same manner as in Example 3 to obtain the compounds shown in Table 3 below.

[0054]

[Table 5]

Example 6 (R)-(2-Pentadecanoyloxy-3-tridecyloxycarbonylpropyl) trimethylammonium chloride obtained in Example 2 (1.5 g; 2.48 mmo)
l) and sodium nicotinate (3.0 g; 20.7 m)
mol) of tetrahydrofuran-ethyl acetate (1: 1)
15 ml of water is added to 30 ml of the suspension, and the mixture is stirred at room temperature for 46.5 hours. The organic layer is separated, washed with 10 ml of water, the solvent is distilled off under reduced pressure, and the residue is azeotropically distilled with ethyl acetate. The residual oily substance was dissolved in 20 ml of diethyl ether, a trace amount of insoluble matter was filtered off, the diethyl ether was distilled off under reduced pressure, and then dried at room temperature under reduced pressure to obtain (R)-(2-pentadecanoyloxy-3.
1.62 g of tridecyloxycarbonylpropyl) trimethylammonium nicotinate are obtained as a colorless solid.

M. p. : 62-68 ° C IR (Nujol) cm ^-1 : 1740, 1610 NMR (CDCl ₃ ) δ: 0.88 (6H, t, J =
6.7 Hz), 1.26 (42H, brs), 1.56
-1.63 (4H, m), 2.25-2.31 (2H,
m), 2.77 (1H, dd, J = 17, 5.7H)
z), 2.82 (1H, dd, J = 17, 6.9H)
z), 3.49 (9H, s), 3.97-4.18 (3
H, m), 4.35 (1H, brd), 5.63-5.
71 (1H, m), 7.25 (1H, dd, J = 7.
7, 4.8 Hz), 8.30 (1H, dt, J = 7.
7, 1.8 Hz), 8.56 (1 H, m), 9.23
(1H, brs).

Examples 7 to 11 The corresponding raw material compounds are treated in the same manner as in Example 1 or 3 to obtain the compounds shown in Tables 4 to 5 below.

[0058]

[Table 6]

[0059]

[Table 7]

Example 12 (R)-(2-tridecanoyloxy-obtained in Example 1)
By treating 3-tridecyloxycarbonylpropyl) trimethylammonium chloride in the same manner as in Example 6, (R)-(2-tridecanoyloxy-3-tridecyloxycarbonylpropyl) trimethylammonium nicotinate was treated as an oil. Get as.

IR (Neat) cm ^-1 : 2920, 28
40,1740 NMR (CDCl ₃ ) δ: 0.88 (6H, t, J =
7.0 Hz), 1.26 (38 H, s), 1.55-
1.65 (4H, m), 2.28 (2H, t, J = 7.
3Hz), 2.76 (1H, dd, J = 5.5, 17H)
z), 2.85 (1H, dd, J = 7.3, 17H
z), 3.46 (9H, s), 4.00-4.20 (3
H, m), 4.34 (1H, d, J = 14 Hz), 5.
65-5.68 (1H, m), 7.20-7.25 (1
H, m), 8.31 (1H, dt, J = 7.8, 1.9)
Hz), 8.56 (1H, dd, J = 1.1, 4.6H
z), 9.22 (1H, s).

Examples 13 to 14 The corresponding starting compounds are treated in the same manner as in Example 1 or 3 to obtain the compounds shown in Table 6 below.

[0063]

[Table 8]

Example 15 (R)-(3-Carboxy-2-propionyloxypropyl) trimethylammonium chloride and 1-bromoundecane were treated in the same manner as in Example 1 (however, saturated saline solution was added to saturated sodium nitrate solution). Instead of the aqueous solution, the reaction time is 20 minutes, and (R)-(3-undecyloxycarbonyl-2-propionyloxypropyl) trimethylammonium nitrate is obtained.

M. p. : 68-70 ° C IR (Nujol) cm ^-1 : 1740 NMR (CDCl ₃ ) δ: 0.88 (3H, t, J =
6.9 Hz), 1.14 (3H, t, J = 7.5H
z), 1.25 (16H, brs), 1.55-1.6
5 (2H, m), 2.39 (2H, q, J = 7.5H
z), 2.75 (1H, dd, J = 17, 5.9H)
z), 2.82 (1H, dd, J = 17, 6.7H
z), 3.35 (9H, s), 4.00-4.10 (4
H, m), 5.60-5.70 (1H, m).

Example 16 (R)-(3-Carboxy-2-propionyloxypropyl) trimethylammonium chloride and 1-bromotridecane were treated in the same manner as in Example 1 (however, saturated saline solution was mixed with saturated nitric acid solution). (Instead of sodium aqueous solution), (R)-(2-propionyloxy-3-tridecyloxycarbonylpropyl) trimethylammonium nitrate is obtained.

M. p. : 79-80 ° C IR (Nujol) cm ^-1 : 1740 NMR (CDCl ₃ ) δ: 0.88 (3H, t, J =
7.0 Hz), 1.14 (3H, t, J = 7.3H)
z), 1.26 (20H, brs), 1.55-1.6
5 (2H, m), 2.39 (2H, q, J = 7.3H
z), 2.75 (1H, dd, J = 17, 5.9H)
z), 2.82 (1H, dd, J = 17, 6.6H)
z), 3.35 (9H, s), 4.00 (2H, d, J
= 5.1 Hz), 4.00-4.10 (2H, m),
5.60-5.70 (1H, m).

Example 17 (R)-(3-Carboxy-2-propionyloxypropyl) trimethylammonium chloride and 1-pentadecanol were treated in the same manner as in Example 3 (except that the extract was an aqueous sodium nitrate solution). Process),
(R)-(2-propionyloxy-3-pentadecyloxycarbonylpropyl) trimethylammonium nitrate is obtained.

M. p. : 83.5-84.5 ° C IR (Nujol) cm ^-1 : 1740 NMR (CDCl ₃ ) δ: 0.88 (3H, t, J =
7.0 Hz), 1.14 (3H, t, J = 7.6H)
z), 1.26 (24H, brs), 1.55-1.6
5 (2H, m), 2.39 (2H, q, J = 7.7H
z), 2.75 (1H, dd, J = 17, 5.9H)
z), 2.82 (1H, dd, J = 17, 6.6H)
z), 3.35 (9H, s), 4.00-4.10 (4
H, m), 5.60-5.70 (1H, m).

Examples 18 to 26 The corresponding starting compounds are treated in the same manner as in Examples 1, 3 or 15 to obtain the compounds shown in Tables 7 to 10 below.

[0071]

[Table 9]

[0072]

[Table 10]

[0073]

[Table 11]

[0074]

[Table 12]

Example 27 By treating (R)-(3-carboxy-2-pentanoyloxypropyl) trimethylammonium chloride and 1-bromotridecane in the same manner as in Example 1, provided that saturated saline solution was saturated. (Replace with aqueous solution of sodium sulfate), (R)-(3-tridecyloxycarbonyl-2
-Pentanoyloxypropyl) trimethylammonium 1/2 sulfonate is obtained.

M. p. :> 57 ° C. IR (Nujol) cm ⁻¹ : 1740 NMR (CDCl ₃ ) δ: 0.88 (3H, t, J =
6.9 Hz), 0.90 (3H, t, J = 7.3H)
z), 1.26-1.38 (22H, m), 1.50-
1.61 (4H, m), 2.29 (2H, t, J = 7.
6Hz), 2.83 (1H, dd, J = 17, 7.2H
z), 3.08 (1H, dd, J = 17, 4.5H
z), 3.44 (9H, s), 3.76 (1H, dd,
J = 14, 9.6 Hz), 3.95-4.03 (2H,
m), 4.51 (1H, brd), 5.69-5.77.
(1H, m).

Examples 28 to 92 Corresponding raw material compounds were prepared according to Examples 1, 3, 6, 15, 17 or 2.
By treating in the same manner as in 7, compounds shown in Tables 11 to 42 below are obtained.

[0078]

[Table 13]

[0079]

[Table 14]

[0080]

[Table 15]

[0081]

[Table 16]

[0082]

[Table 17]

[0083]

[Table 18]

[0084]

[Table 19]

[0085]

[Table 20]

[0086]

[Table 21]

[0087]

[Table 22]

[0088]

[Table 23]

[0089]

[Table 24]

[0090]

[Table 25]

[0091]

[Table 26]

[0092]

[Table 27]

[0093]

[Table 28]

[0094]

[Table 29]

[0095]

[Table 30]

[0096]

[Table 31]

[0097]

[Table 32]

[0098]

[Table 33]

[0099]

[Table 34]

[0100]

[Table 35]

[0101]

[Table 36]

[0102]

[Table 37]

[0103]

[Table 38]

[0104]

[Table 39]

[0105]

[Table 40]

[0106]

[Table 41]

[0107]

[Table 42]

[0108]

[Table 43]

[0109]

[Table 44]

Reference Example 1 75-8 of n-pentadecanoic acid (25 g; 103 mmol) and thionyl chloride (3.15 g; 26.5 mmol) were added.
After stirring at 0 ° C. for 3 hours, the temperature was adjusted to 60 ° C., and L-carnitine (4.27 g; 26.5 mmol) trichloroacetic acid 2
Add 5 g solution and stir at 80 ° C. for 3 hours under argon atmosphere. The reaction solution is poured into 100 ml of stirred diethyl ether, the precipitate is collected by filtration, washed with diethyl ether, and dried to obtain 11.8 g of the crude target product as a colorless solid. The crude product (11.8 g) was recrystallized from isopropanol to give colorless needle crystals (R)-(3-carboxy-2).
9.38 g of pentadecanoyloxypropyl) trimethylammonium chloride are obtained.

M. p. 167-169 ° C IR (Nujol) cm ^-1 : 3020-2480,17
40,1710 NMR (DMSO-d ₆ ) δ: 0.85 (3H, t, J
= 6.7 Hz), 1.24 (22H, brs), 1.4
7-1.57 (2H, m), 2.23-2.40 (2
H, m), 2.62-2.76 (2H, m), 3.12
(9H, s), 3.68 (1H, brd), 3.81
(1H, dd, J = 14, 8.1Hz), 5.42-
5.49 (1H, m).

Reference Examples 2 to 14 The corresponding starting compound was treated in the same manner as in Reference Example 1 to give the following 43rd
~ 46 to obtain the compounds described in Table.

[0113]

[Table 45]

[0114]

[Table 46]

[0115]

[Table 47]

[0116]

[Table 48]

Reference Example 15 L-carnitine (2.0 g; 12.4 mmol) was dissolved in 3 ml of trifluoroacetic acid with heating (60 ° C.), 8 ml (37.2 mmol) of 10-undecenoyl chloride was added, and the container was tightly closed. Stir vigorously for 5 minutes by hand until homogeneous at the same temperature. After becoming a homogeneous system, the mixture is further stirred at the same temperature for 10 minutes. After distilling off the solvent of the reaction solution, the residue is dissolved in 100 ml of petroleum ether, poured into 100 ml of ice water, and stirred at room temperature for 30 minutes. Then, 100 ml of ethanol-100 ml of ether is added to these mixed solutions for extraction. The aqueous layer is further extracted twice with 60 ml of ethanol-60 ml of ether. 120 ml of n-butanol in the separated water layer
Is added, and water is appropriately added so as to form two layers, and extraction is performed. n
-The butanol layer is 40 ml of water and 40 parts of phosphate buffer solution.
Wash with ml (67 mmol; pH 7.2), 40 ml of water. The n-butanol layer was separated, the solvent was evaporated, the residue was azeotropically distilled with toluene and ethyl acetate, and the residual oily substance was recrystallized from ethyl acetate to obtain (R)-[3-carboxy-2- (1
1.81 g of 0-undecenoyloxypropyl)] trimethylammonium chloride are obtained as colorless crystals.

M. p. : 154-156 ℃ IR (Nujol) cm -1: 1740 NMR (DMSO-d 6) δ: 1.20-1.40 (1
0H, m), 1.45-1.60 (2H, m), 1.9
5-2.05 (2H, m), 2.25-2.35 (2
H, m), 2.65 (2H, d, J = 6.1 Hz),
3.11 (9H, s), 3.66 (1H, d, J = 13
Hz), 3.81 (1H, dd, J = 14, 8.3H)
z), 4.90-5.05 (2H, m), 5.40-
5.50 (1H, m), 5.70-5.90 (1H,
m).

Reference Example 16 L-carnitine and linoleoyl chloride were used as Reference Example 1.
By treating in the same manner as in 5, (R)-(3-carboxy-2-linoleoyloxypropyl) trimethylammonium chloride is obtained.

IR (Neat) cm ^-1 : 1740 NMR (DMSO-d ₆ ) δ: 0.86 (3H, t, J
= 6.7 Hz), 1.20-1.40 (14H, m),
1.45-1.60 (2H, m), 1.95-2.05
(4H, m), 2.25-2.35 (2H, m), 2.
68 (2H, d, J = 5.9Hz), 2.74 (2H,
t, J = 5.5 Hz), 3.10 (9H, s), 3.6
2 (1H, d, J = 13Hz), 3.81 (1H, d
d, J = 15, 8.3 Hz), 5.25-5.40 (4
H, m), 5.40-5.50 (1H, m).

Reference Example 17 L-carnitine and dodecanoyl chloride were used as Reference Example 1.
The same treatment as in (R)-(3-carboxy-2-dodecanoyloxypropyl) trimethylammonium chloride is obtained.

M. p. 174-176 ° C IR (Nujol) cm ^-1 : 1735,1705 NMR (DMSO-d ₆ ) δ: 0.86 (3H, t, J
= 6.8 Hz), 1.24 (16H, brs), 1.4
8-1.57 (2H, m), 2.24-2.40 (2
H, m), 2.63-2.77 (2H, m), 3.12.
(9H, s), 3.69 (1H, brd), 3.82
(1H, dd, J = 14, 8.2Hz), 5.43-
5.49 (1H, m).

MS (ESI) m / z: 366 [(MNa
-HCl) ^<+> ], 344 [(MH-HCl) ^<+> ].

Reference Example 18 L-carnitine and octanoyl chloride were used as Reference Example 1.
The same treatment as in (R)-(3-carboxy-2-octanoyloxypropyl) trimethylammonium chloride is obtained.

M. p. 176-177 ° C IR (Nujol) cm ^-1 : 1735, 1705 NMR (DMSO-d ₆ ) δ: 0.86 (3H, t, J
= 6.7 Hz), 1.25 (8H, brs), 1.48
-1.58 (2H, m), 2.24-2.40 (2H,
m), 2.63-2.77 (2H, m), 3.13 (9)
H, s), 3.70 (1H, brd), 3.82 (1
H, dd, J = 14, 8.1 Hz), 5.42-5.4.
9 (1H, m), 12.8 (1H, br).

MS (ESI) m / z: 288 [(MH-
HCl) ⁺ ].

Reference Example 19 Ethylsuccinyl chloride (17.6 g; 107 mmo)
1) and water (1.28 g; 71.0 mmol) 60 to 7
After stirring at 0 ° C. for 1.5 hours, a solution of L-carnitine (3.83 g; 23.8 mmol) dissolved in 12 g of trifluoroacetic acid with heating (40 ° C.) was added to the mixture. After stirring the mixture at 60-70 ° C. for 21.5 hours,
Cool to room temperature. To the mixture, add diethyl ether 200
ml was added and the resulting oil was added to diethyl ether 200
Wash twice with ml. The residual oil is solidified by adding 150 ml of tetrahydrofuran. The obtained solid was pulverized, collected by filtration, washed with tetrahydrofuran, and dried to give (R)-[3-carboxy-2- (3-ethoxycarbonylpropionyloxy) propyl] trimethylammonium chloride 6.5.
g is obtained as a colorless solid.

M. p. : 97-99 ° C IR (Nujol) cm ^-1 : 3400 (br), 173
0 NMR (DMSO-d ₆ ) δ: 1.18 (3H, t, J
= 7.1 Hz), 2.54-2.64 (4H, m),
2.68-2.71 (2H, m), 3.13 (9H,
s), 3.69 (1H, brd), 3.85 (1H, d
d, J = 14, 8.6 Hz), 4.06 (2H, q, J
= 7.1 Hz), 5.44-5.51 (1 H, m), 1
2.8 (1H, br).

MS (ESI) m / z: 290 [(MH-
HCl) ⁺ ].

[0130]

INDUSTRIAL APPLICABILITY The carnitine derivative according to the present invention [I]
Has an excellent hair-growing action. Moreover, the carnitine derivative according to the present invention has low toxicity and high safety. For example, 3% of a 2% ethanol solution of (R)-(2-tridecanoyloxy-3-tridecyloxycarbonylpropyl) trimethylammonium chloride, which is the active ingredient of the present invention, is used.
No skin abnormality was observed after application for 0 days. Therefore, the carnitine derivative [I] according to the present invention is useful as a hair-growing agent, and an animal (for example, sheep or goat) that supplies humans or hair products (for example, products made of wool or cashmere).
Can be effectively used for promoting hair growth or hair growth.
Further, the carnitine derivative [I] according to the present invention is used to prevent androgenetic alopecia, senile alopecia, resting alopecia, gray hair, etc.
It can be used effectively in therapy.

Claims (15)

[Claims] 1. A compound of the general formula [I] [In the formula, R ^{1 to} R ³ are alkyl groups having 1 to 6 carbon atoms, R ⁴
Is a substituted or unsubstituted aliphatic acyl group having 3 to 31 carbon atoms,
R ⁵ is a substituted or unsubstituted C ³ to C 31 alkyl group or a substituted or unsubstituted C 3 to C 31 alkenyl group, X
^- represents an anion of an acid acceptable in pharmaceutically. ] A hair restorer containing a carnitine derivative represented by the following as an active ingredient. 2. R ^{1 to} R ^{3 each} have an alkyl group having 1 to 6 carbon atoms, and R ⁴ has 3 carbon atoms which may be substituted with a group selected from a hydroxyl group and an alkoxycarbonyl group having 2 to 7 carbon atoms.
To 31 aliphatic acyl groups, R ⁵ is a hydroxyl group and 2 to 2 carbon atoms.
C3-C31 alkyl group which may be substituted by a group selected from C7 alkoxycarbonyl group or C3 which may be substituted by a group selected from a hydroxyl group and a C2-C7 alkoxycarbonyl group. The hair restorer according to claim 1, which is an alkenyl group of about 31. 3. R ^{1 to} R ³ are alkyl groups having 1 to 6 carbon atoms, R ⁴ is an aliphatic acyl group having 3 to 31 carbon atoms, and R ⁵ is an alkyl group having 3 to 31 carbon atoms or 3 to 3 carbon atoms. The hair restorer according to claim 1, which has 31 alkenyl groups. 4. R ⁴ is a propionyl group, butyryl group, isobutyryl group, crotonoyl group, methacryloyl group, valeryl group, isovaleryl group, pivaloyl group, hexanoyl group, 4-methylvaleryl group, sorbinoyl group, heptanoyl group, octanoyl group, 2 -Propylvaleryl group,
Nonanoyl group, decanoyl group, undecanoyl group, 1
0-undecenoyl group, dodecanoyl group, tridecanoyl group, tetradecanoyl group, pentadecanoyl group, hexadecanoyl group, heptadecanoyl group, octadecanoyl group, oleoyl group, elaidyl group, linoleoyl group, linolenoyl group, nonadecanoyl group, 2, 6, 1
0,14-tetramethylpentadecanoyl group, icosanoyl group, 3,7,11,15-tetramethylhexadecanoyl group, arachidoyl group, henicosanoyl group, docosanoyl group, tricosanoyl group, tetracosanoyl group,
Pentacosanoyl group, hexacosanoyl group, heptacosanoyl group, octacosanoyl group, nonacosanoyl group, triacontanoyl group or hentriacontanoyl group, R
⁵ is a propyl group, isopropyl group, butyl group, isobutyl group, 1-methylpropyl group, 1,1-dimethylethyl group, pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1,1- Dimethylpropyl group, 1,2-dimethylpropyl group, 2,2-dimethylpropyl group, 1-ethylpropyl group, 2-ethylpropyl group, hexyl group, isohexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 1
-Ethylbutyl group, 2-ethylbutyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,2-dimethylbutyl group, 2,3-
Dimethylbutyl group, 3,3-dimethylbutyl group, 1-ethyl-1-methylpropyl group, 1-ethyl-2-methylpropyl group, 2-ethyl-1-methylpropyl group, 2-
Ethyl-2-methylpropyl group, 1-methyl-2-ethylpropyl group, 1,1,2-trimethylpropyl group,
1,2,2-trimethylpropyl group, heptyl group, octyl group, 2-propylpentyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group Group, nonadecyl group, icosyl group,
Henicosyl group, docosyl group, tricosyl group, tetracosyl group, pentacosyl group, hexacosyl group, heptacosyl group, octacosyl group, nonacosyl group, triacontyl group, hentriacontyl group, 2-propenyl group, 1-methylethynyl group, 10-undecenyl group , 14-pentadecenyl group, 3,7,11,15-tetramethyl-2-
Hexadecenyl group, 20-henicosenyl group or 30-
The hair restorer according to claim 3, which has a Hentriacontenyl group. 5. R ^{1 to} R ³ are alkyl groups having 1 to ⁴ carbon atoms, R ⁴ is an aliphatic acyl group having 3 to 18 carbon atoms, and R ⁵ is an alkyl group having 3 to 21 carbon atoms or 3 to 4 carbon atoms. The hair restorer according to claim 1, which has 21 alkenyl groups. 6. R ⁴ is a propionyl group, isobutyryl group, valeryl group, hexanoyl group, 4-methylvaleryl group, heptanoyl group, 2-propylvaleryl group, nonanoyl group, undecanoyl group, 10-undecenoyl group,
Tridecanoyl group, tetradecanoyl group, pentadecanoyl group, hexadecanoyl group, heptadecanoyl group or linoleoyl group, R ⁵ is propyl group, pentyl group, 2-
The hair restorer according to claim 5, which is a methylbutyl group, an isohexyl group, a heptyl group, a nonyl group, a decyl group, an undecyl group, a dodecyl group, a tridecyl group, a tetradecyl group, a pentadecyl group, a henicosyl group or a 10-undecenyl group. 7. R ^{1 to} R ³ are alkyl groups having 1 to ⁴ carbon atoms, R ⁴ is an aliphatic acyl group having 3 to 15 carbon atoms, and R ⁵ is an alkyl group having 3 to 15 carbon atoms or 3 to ⁵ carbon atoms. The hair restorer according to claim 1, which has 15 alkenyl groups. 8. R ⁴ is a propionyl group, isobutyryl group, valeryl group, 4-methylvaleryl group, hexanoyl group, heptanoyl group, undecanoyl group, 10-undecenoyl group, tridecanoyl group or pentadecanoyl group, R ⁵ is a propyl group, The hair restorer according to claim 7, which is a pentyl group, a 2-methylbutyl group, a heptyl group, a nonyl group, an undecyl group, a dodecyl group, a tridecyl group, a tetradecyl group or a pentadecyl group. 9. R ^{1 to} R ³ are alkyl groups having 1 to 6 carbon atoms, R ⁴ is an aliphatic acyl group having ⁴ to 31 carbon atoms, and R ⁵ is an alkyl group having 11 to 31 carbon atoms. The hair restorer described. 10. The hair restorer according to claim 1, wherein the sum of the carbon number of the aliphatic acyl group in R ⁴ and the carbon number of the alkyl group or alkenyl group in R ⁵ is 6 to 34. 11. The hair restorer according to claim 3, wherein the sum of carbon numbers of R ⁴ and R ⁵ is 6 to 34. 12. The sum of carbon numbers of R ⁴ and R ⁵ is 14 to 26.
The hair restorer according to claim 3. 13. The hair restorer according to any one of claims 1 to 12, which is a promoter for hair growth and hair growth of humans or animals. 14. The hair restorer according to any one of claims 1 to 12, which is a prophylactic / therapeutic agent for androgenetic alopecia, senile alopecia, alopecia areata or gray hair. 15. A general formula: [In the formula, R ^{1 to} R ³ represent a methyl group, and R ⁴ and R ⁵ are
R ⁴ is a pentadecanoyl group and R ⁵ is an undecyl group; R ⁴ is a valeryl group and R ⁵ is a tridecyl group; R
⁴ is a propionyl group and R ⁵ is an undecyl group; R ⁴
R ⁵ is R ⁴ a valeryl group; but R ⁵ a tridecanoyl group pentyl group; R ⁵ is nonyl group comprising R ⁴ is heptanoyl group; R ⁵ R ⁴ is an undecanoyl pentyl group Is an undecyl group; R ⁴ is an undecanoyl group, R ⁵ is a heptyl group; R ⁴ is a tridecanoyl group, R ⁵ is a heptyl group; R ⁴ is an isobutyryl group, R ⁵ is a tridecyl group; R ⁴ is propionyl R ⁵ is a tridecyl group; R ⁴ is a 4-methylvaleryl group; R ⁵ is a dodecyl group; R ⁴ is a 4-methylvaleryl group; R ⁵ is a tridecyl group; R ⁴ is an isobutyryl group R ⁵ is a tetradecyl group; R ⁴ is a valeryl group, R ⁵ is a pentadecyl group; R ⁴ is a propionyl group, R ⁵ is a pentadecyl group; R ⁴ is a hexanoyl group and R ⁵ is an undecyl group. The table , X ^- represents an anion of an acid acceptable in pharmaceutically. ] The carnitine derivative shown by these.