JPH0478606B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention provides a novel hair growth/hair growth agent, more specifically,
The present invention relates to a hair growth/growth agent containing 5,8,11,14,17-eicosapentanoic acid or its ester as an active ingredient. [Prior art and its problems] 5,8,11,14,17-eicosapentaenoic acid (hereinafter referred to as "EPA") is expressed by the following formula () This compound is known to have the effect of lowering plasma cholesterol in the human body and can be used for the prevention or treatment of thrombosis. In addition, although hair growth agents and hair growth agents containing various medicinal ingredients have been known, none that exhibit sufficient effects have yet been provided. [Means for solving the problem] Regarding EPA and its ester, the present inventor has
As a result of researching their effects, it was discovered that they have hair growth and hair growth effects, and the present invention was completed. That is, the present invention provides a hair growth/growth agent containing EPA or its ester as an active ingredient. The EPA used in the present invention is already a known compound, and for example, it can be obtained with high purity by decomposing EPA-ethyl ester obtained by the method described in JP-A-58-8037 with caustic potassium in ethanol. can be obtained as It can also be used in salt form. Further, as the ester of EPA, esters with various alcohols are used, and among them, esters with glycerin are preferred. Examples of this glyceride include diglycerides and triglycerides shown below. 1,2,3-tri(eicosapentanoyl)glyceride [EPA-TG] 1,2-di(eicosapentaenoyl)glyceride [1,2-EPA-DG] (R represents hydrogen or an acyl group) 1,3-di(eicosapentaenoyl)glyceride [1,3-EPA-DG] These are, for example, halogenated EPA and EPA
- Manufactured by reacting glycerin with halide (Patent application 1986-86889)
issue). These glycerides are generally obtained as a mixture of each, but they can be isolated and used alone or as a mixture. The hair growth/growth agent of the present invention may be formulated into a conventional formulation such as a medicated cream, medicated lotion, medicated hair tonic, hair tonic, hair liquid, hair cream, milky lotion, shampoo, or conditioner according to a conventional method. As the compounding base, water, alcohols, oils and fats, surfactants, etc. may be used, and other medicinal ingredients such as hormones, vitamins, amino acids, etc. can also be compounded. In the present invention, the blending amount of the active ingredient can be appropriately selected, but it is usually preferably 0.01 to 10% by weight (hereinafter simply expressed as %) based on the total amount of the hair growth/growth preparation. [Effects of the Invention] The hair growth and hair growth agent of the present invention has excellent hair growth and hair growth effects, as shown in the examples below, and
EPA and its esters have the advantage of being safe as they have extremely low toxicity. [Example] Next, reference examples and examples will be given and explained. Reference example 1 () EPA-ethyl ester 40g (0.121mol)
and 10% KOH ethanol [8.15g as KOH
(0.145 mol)] and introduced _N2 gas (150 mol)].
ml/min) and refluxed at 75-76.5°C for 1 hour. The reaction mixture was cooled to room temperature, adjusted to pH 2 with 10% HCl water, and since inorganic salts were precipitated, 50 ml of water was added to dissolve them, and the mixture was extracted twice with 100 ml and 50 ml of n-hexane. The extract was dried with anhydrous magnesium sulfate,
The solvent was distilled off at 40℃ under reduced pressure, leaving 35.9g of oily EPA.
(yield 98.1%). (2) 29.5 g (0.232 mol) of oxalyl chloride was added dropwise to 35.1 g (0.116 mol) of EPA at room temperature while introducing N ₂ gas. Next, the reaction was carried out at 65 to 75°C for 4 hours, and after the reaction, excess oxalyl chloride was distilled off using an evaporator. The residue was distilled under reduced pressure and the fractions from 144℃/1mmHg to 187℃/2mmHg were collected and 18.78g of EPA-chloride (yield 50.4%)
I got it. () Glycerin 1.81g (0.0197mol), quinoline
Prepare 10.8g (0.084mol) and 80.1g of chloroform, and add 18.0g of EPA-chloride to this.
(0.056 mol) was gradually added dropwise. This is 72-80
It was refluxed at ℃ for 3.5 hours. After cooling the reaction solution, it was poured into 540ml of petroleum ether, and 0.5N aqueous sulfuric acid solution was added.
300 ml was added under stirring, stirred for 10 minutes, and left to stand for 30 minutes. The layers were separated, and 300 ml of a 5% aqueous potassium carbonate solution was added to the upper layer to separate the layers. 300ml of water in the upper layer
100 ml of saturated saline was added to the upper layer to separate the layers, and the upper layer was collected. After drying this with anhydrous magnesium sulfate, petroleum ether was distilled off using an evaporator to obtain 15.15 g of an oily substance. A glass column was filled with 500 g of silica gel using special grade benzene, and a solution of 10 g of the above oil dissolved in 100 ml of special grade benzene was added thereto. Next, the same benzene 8 was used for elution, and 300 ml fractions were collected. This fraction was analyzed using TLC (Kieselgel 60F ₂₅₄ , developing solvent: benzene, confirmation: I ₂
The eluate was confirmed using Vapor), the same solution was collected, and the solvent was distilled off under reduced pressure to obtain the following substance.

[Table] Example 1 A sample was a mixture of EPA sodium (EPA purity 96.8%) in 50% ethanol at a ratio of 1%. The samples were freshly mixed and prepared each time they were used. 50% ethanol was used as a control. Two groups of 42-week-old male Wistar rats (10 rats per group), a total of 20 rats, were used. The dorsal coat of the rat was removed using a shaver on each side of the spine in an area of 4 x 4 ^cm2 . A 3×3 cm ² area was drawn in the center of the hair removal area with an oil-based pen to serve as the application site for the test liquid. Starting from the day after the above procedure, twice a day in the morning and evening, 7 times in a row
For days, sample or control solution is placed in each section in the arrangement shown in Table 1.
0.2 ml was applied, and on the 8th day, the degree of elongation of the coat and the state of hair growth were observed under a stereomicroscope. The degree of elongation of the coat was expressed as an index according to the criteria in Table 2.

【table】

[Table] In addition, in order to eliminate differences in application sites, the placement of C and E was crossed between groups, and both C and E samples were applied to all individuals to equalize individual differences. . The results are shown in Table 3, and the results of the significant difference test between each group in Table 3 are shown in Table 3-2.

【table】

[Table] * Mean value ± standard error

[Table] As shown in Table 3 and Table 3-2, significance level p=
When set to 0.05, a significant difference was observed between the groups in column A, but no difference was observed between the groups in column B. That is, there was a significant difference between C and E regardless of the area where the sample was applied, and the hair at the area where E was applied showed significant elongation compared to C. In addition, when observed under a microscope, the tip of the hair showed the shape of a torn end due to shaving in the basic condition of hair removed from the back, whereas most of the elongated hair was new hair with a sharp tip. shape was observed. From the above results, it was shown that EPA sodium salt promotes hair elongation, and particularly promotes new hair growth and elongation. Example 2 A total of 10 male Wistar rats (40 weeks old), 2 groups of 5 rats per group, were used. under ether anesthesia,
4 cm x 8 dorsal coats on the left and right sides of the midline
It was shaved to a size of cm, and two 3 cm x 3 cm sections were drawn on one side, and a total of 4 sections were drawn with a permanent marker so that they were symmetrical on both sides. From the next day after this procedure, each sample in Table 4 was placed twice a day in a row according to the arrangement in Table 5.
0.2 ml was applied to each section of the hair removal area for 10 days. On the 11th day, the degree of fur elongation was examined based on the criteria shown in Table 2.

【table】

【table】 The results are shown in Table 6.

[Table] The degree of coat elongation of EPA-G shown in Table 6 is expressed as an index for each application area as shown in Table 7.
A significant difference was observed at P<0.05.

[Table] Example 3 Twenty 45-week-old Wistar male rats were used. After cutting the rat's back coat with a shaver, the hair was completely removed using a commercially available hair removal cream, and the remaining cream was completely washed away with warm water. One week later, the hair-removed area on each rat's back was observed to be a mixture of areas where hair growth started and areas where there was no hair. At this point, the hairless area was drawn with an oil-based pen, and the left and right dorsal areas of each individual were divided into a control area and a sample application area. Starting from the day after the above procedure (9th day after hair removal), the samples shown in Table 8 were applied twice a day in the morning and evening for 10 consecutive days.

[Table] The degree of hair growth was evaluated according to the criteria shown in Table 9 on the 11th day after the start of application.

【table】 Experimental result

[Table] As shown in Table 10, the average index for control sites
1.30, whereas in the EPA-Na applied area
It showed a significantly large value of 1.90 (p<0.05), indicating a hair growth promoting effect.

Claims (1)

[Scope of Claims] 1. A hair growth/growth agent containing 5,8,11,14,17-eicosapentaenoic acid or its ester as an active ingredient. 2. The hair growth/growth agent according to claim 1, wherein the ester of 5,8,11,14,17-eicosapentaenoic acid is diglyceride or triglyceride.