JP2001048756A - Hair grower - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a hair grower having a promoting action on peripheral blood circulation of scalp and an activating action on a hair-mother cell, excellent hair growing effect and a preventing effect on depilation by making the hair growing cosmetic include a bis(hydroxyphenyl)pentadienone compound. SOLUTION: This hair growing composition contains preferably 0.0001-10.0 wt.% more preferably 0.005-5.0 wt.% of a bis(hydroxyphenyl)pentadienone compound of the formula (R1 is H, CH3 or C2H5; OR1 shows 1-3 substituents on each aromatic ring) [e.g. 1,5-bis(p-hydroxy-m-methoxyphenyl)-1,4-pentadien-3-one]. The compound of the formula can be produced, for example, by a method for protecting the hydroxyl group of 3-methoxy-4-hydroxybenzaldehyde, 4- hydroxybenzaldehyde, etc., with 3,4-dihydropyran, methoxymethyl chloride, etc., then, condensing the protected substance with acetone and finally deprotecting the condensed substance with an acid, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hair nourishing cosmetic having an excellent hair-growth effect and an effect of preventing hair loss.

[0002]

2. Description of the Related Art Conventionally, hair restoration cosmetics containing a blood circulation promoting substance such as pepper tincture and nicotinic acid derivative, and amino acids and vitamins which are nutrients of hair are known. Have been.
Further, many medical hair restorers and cosmetics containing a component having an effect of preventing sebaceous gland hypertrophy and a component having an androgenic inhibitory effect have been proposed.

[0003] However, conventionally used blood circulation promoting substances are highly irritating to the skin, and the amount thereof is limited,
The disadvantage is that the duration of blood circulation promotion is short.

[0004] By the way, androgenetic alopecia is said to be one of the causes of the excessive action of male hormones. Phenomena such as poor circulation, decreased activity of hair matrix cells, enlargement of sebaceous glands, fibrosis of the scalp, and the like are considered. It is presumed that it is caused by complicated intertwining.

[0005] However, even if an anti-androgen agent is simply used as a hair restorer to suppress hair matrix cell activity reduction and sebaceous gland hypertrophy, which are said to be caused by excessive action of androgen, the hair growth effect is exhibited. At present it does not reach. In addition, good results cannot be obtained even when the hair matrix activator or the blood circulation promoter is used alone.

As a means for solving the above-mentioned problems, a hair restorer composition containing fatty acids and alcohols having an odd carbon number, hydroxypropyl alcohol and a lower alcohol disclosed in JP-A-5-58850 is disclosed. Numerous hair growth and hair growth, including a hair growth agent containing certain carboxyl betaines described in JP-A-5-139936, a hair growth cosmetic containing an acid mucopolysaccharide and a hop extract described in JP-A-5-170625, and the like. Agents have been proposed, but using a substance that promotes peripheral blood flow and activates hair matrix cells alone has not found any remarkable hair-growth effect, and has a satisfactory effect in the composition. In fact, there was room for improvement in the hair growth effect and the hair loss prevention effect.

[0007]

In view of such circumstances, as a result of diligent studies on substances having a promoting action on peripheral blood flow of the scalp and activating hair matrix cells, bis-hydroxyphenyl represented by the following general structural formula 2 is obtained. Hair finding cosmetics containing a pentadiene-on compound have been found to exhibit an excellent hair-growth effect, a hair loss-preventing effect that is the object of the present invention, and have led to the completion of the present invention. What is needed is to provide a hair restoration cosmetic having an excellent hair-growth effect and an effect of preventing hair loss.

[0008]

Embedded image (However, R ₁ represents H, CH ₃ , C ₂ H _5. Also, the OR ₁ group represents 1 to 3 substitutions on each aromatic ring.)

The above-mentioned object is achieved by a hair restoration cosmetic comprising at least one bis-hydroxyphenyl-pentadiene-one compound represented by the following general structural formula (3).

[0010]

Embedded image (However, R ₁ represents H, CH ₃ , C ₂ H _5. Also, the OR ₁ group represents 1 to 3 substitutions on each aromatic ring.)

[0011]

Embodiments of the present invention will be described below in detail.

The bis-hydroxyphenyl pentadiene-one compound (BHPPO) used in the present invention includes 1,5-bis (p-hydroxy-m-
(Methoxyphenyl) -1,4-pentadien-3-one, 1,5-bis (p-hydroxyphenyl) -1,4
-Pentadien-3-one and the like.

The bis-hydroxyphenyl pentadiene-one compound (BHPPO) used in the present invention is produced by a known synthesis method. Specifically, for example, 3-methoxy-4-hydroxybenzaldehyde, -Hydroxybenzaldehyde, 2,4-dihydroxybenzaldehyde and the like are protected with a hydroxy group with 3,4-dihydropyran, methoxymethyl chloride and the like, then condensed with acetone, and finally deprotected with an acid to obtain the desired bis. A hydroxyphenyl pentadiene on compound can be obtained.

The amount of the bis-hydroxyphenyl-pentadiene-one compound used in the present invention was determined by examining the range of the hair-growth effect and the hair loss-preventing effect which are the object of the present invention. With reference to 0.
It may be 0001 to 10.0% by weight (hereinafter abbreviated as wt%), and more preferably 0.005 to 5.0% by weight.
It is.

The hair restoration cosmetic of the present invention includes known vitamin E derivatives such as vitamin E, vitamin E acetate and vitamin E nicotinate, pantothenic acid derivatives such as pantoenyl alcohol and calcium pantothenate, benzyl nicotinate and nicotinic acid. Nicotinic acid derivatives such as amides, glycyrrhizic acid, dipotassium glycyrrhizinate, glycyrrhizic acid derivatives such as monoammonium glycyrrhizinate, glycyrrhetinic acid, glycyrrhetinic acid derivatives such as stearyl glycyrrhetinate, antiandrogens, assembly extracts, Korean ginseng extract, Duke extract, Pepper tincture, diisopropylamine dichloroacetate, γ-aminobutyric acid derivative, and the like can be appropriately combined and compounded as long as the object of the present invention is achieved.

The hair nourishing cosmetic composition of the present invention is produced in a usual manner into dosage forms such as hair tonic, hair lotion, hair treatment, hair cream, hair conditioner, shampoo, rinse, hair gel, hair mist, and hair foam. And can be used.

The hair growth cosmetic composition of the present invention is applied or sprayed on a topical (scalp) intended for the purpose of hair growth, hair growth and / or hair loss prevention according to the dosage form.

The hair nourishing cosmetic composition of the present invention includes a pigment, a fragrance, a bactericide, a preservative, a surfactant, a pigment, a keratolytic agent,
An antioxidant and the like can be appropriately compounded.

[0019]

The present invention will be described in detail below with reference to examples and comparative examples, but the present invention is not limited to these examples. The test method used in the present invention is as follows.

(1) 5α-reductase activity inhibition test. Enzyme source: After sacrifice SD rats (10 weeks old, male),
The prostate is removed and 0.1 M HEPES buffer containing 3 volumes of 0.25 M sucrose (pH 7.0).
Homogenized in 2). The obtained homogenate was centrifuged at 3,000 rpm for 10 minutes to separate a nuclear fraction, and resuspended in the same volume of the above buffer solution to obtain an enzyme solution.

Assay method: The microradioassay method was used for measuring 5α-reductase activity. For more information,
After adding 1.5 nmol of (4-14C) -testosterone and a sample solution and evaporating the solvent, 10 μl of 50 m
M nicotinamide adenine dinucleotide (NA
DPH) and 60 μl of the above buffer solution, and stir.
Preincubation was performed at 7 ° C for 5 minutes. The reaction is 30
Started by adding μl of enzyme solution. 37
After incubating at 60 ° C. for 60 minutes, 0.4 ml of a chloroform: methanol (1: 2) solution was added to stop the reaction, and the mixture was centrifuged at 3,000 rpm for 10 minutes to obtain a sample for analysis.

Analytical method: 50 μl of each sample was subjected to the following two-step thin layer chromatography (TLC).
According to this system, references [Clin. Endocrinol., MJThorn
ton, I.Laing, K.Hamada, AGMessenger and VARanda
ll, 39, 633-639, 1993], it is possible to analyze all androgen metabolites.・ Dichloromethane: diethyl ether (70:10) ・ Chloroform: diethyl ether (90:10) After the TLC plate was air-dried, the testosterone was converted to 5α-dihydrotestosterone by 5α-reductase using a radiochromatography analyzer (Aloka JT601). The conversion was measured. The 5α-reductase inhibition rate was calculated from the conversion rate (A) when no sample was added (control) and the conversion rate (B) of each sample by the following formula. 5α-reductase inhibition rate (%) = [1- (B) /
(A)] × 100 The higher this value is, the more the 5α-reductase activity is inhibited.

(2) Mouse Hair Growth-Promoting Effect Test Method The skin at the center of the back of a C3H mouse (male, 8 weeks old, average weight 35 g) was cut with an electric clipper, and the hair was completely removed with a shaver. From the next day, each sample of Example and Comparative Example was applied to the skin of the test part once a day, 0.2 ml per animal. A group of 10 animals was used for one sample. A non-applied group was provided as a control. On the 14th day after the start of the experiment, the animals were sacrificed and photographs of the skin of the test area were taken. Next,
The photograph was taken into an image analyzer, and the hair growth area (A) of the control non-application group and the hair growth area (B) of the application group (Comparative Example, Example) were determined. Further, the hair growth rate = (B) / (A) was calculated for each animal. The higher the value, the more the effect of promoting hair growth.

(3) Human hair growth promoting effect test method Male test subject 1 in her 30s and 40s with reduced hair growth
The hair at the top of the head was shaved into a circular shape having a diameter of about 7 mm. One and three days after shaving, the method of Hayashi et al. (British Journal of Dermatology, 12
5, p. 123, 1991), the hair growth rate was determined for the hair at the target site (about 30 hairs), and the average value (A)
Was calculated. Next, about 3 ml of the sample of Example or Comparative Example was applied to each subject twice daily in the morning and evening around the test site and massaged well. On the 28th day after the start of the test, the hair growth rate at the same site was measured in the same manner, and the average value (B) was calculated. The effect was determined by comparing the ratio (B) / (A) before and after use of each hair nourishing cosmetic.

(4) Practical test method Twice in the morning and evening twice a day on the head of 20 male pattern baldness patients
The effect after applying the sample for a month was evaluated. The test results are for hair growth and hair loss prevention.
The number of respondents who answered, "Regrowth of raw hair or increase of bristle" and "Reduction of hair loss" were indicated.

Examples 1-5, Comparative Example 1 (Testosterone-5α-reductase activity inhibitory action) In this example, 1,5-bis (p-hydroxy-m-methoxyphenyl) -1,4-pentadiene-3 was used. Ethanol solutions (Examples 1 to 3) of -one (Chemical Formula 4) prepared to the concentration shown in Table 1 and 1,5-bis (p-hydroxyphenyl) -1,4-pentadien-3-one (Chemical Formula 5) Of the ethanol solution (Examples 4 to
5) was used. An ethanol solution was used as a control (Comparative Example 1) instead of the sample solution. These test samples were evaluated by the test for measuring the inhibitory activity of testosterone-5α-reductase activity described above. The results are shown in Table 1. In Comparative Example 1, no activity was observed, whereas 1,5
-Bis (p-hydroxy-m-methoxyphenyl)-
1,4-pentadien-3-one (Examples 1-3) and 1,5-bis (p-hydroxyphenyl) -1,4-pentadien-3-one (Examples 4-5) have higher activity. Admitted.

[0027]

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[0028]

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[0029]

[Table 1]

Examples 6 to 8, Comparative Example 2 (Heart Tonic) In the raw material composition shown in Table 2, as an active ingredient BHPPO, as shown in Table 3, 1,5-bis (p-hydroxy-m-
Methoxyphenyl) -1,4-pentadien-3-one (Chemical Formula 6) was blended to prepare a hair tonic, and the above-described tests were performed.

[0031]

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[0032]

[Table 2]

[0033]

[Table 3]

(1) Preparation method The components belonging to (A) shown in Table 2 were dissolved by heating, the components belonging to (C) dissolved separately and gradually added, and the components (B) were further added to obtain a homogeneous solution. And mixed with stirring.

(2) Characteristics Table 3 shows the results of various tests performed on each hair tonic. As shown in Table 3, Comparative Example 2 had low mouse hair growth promoting effect and human hair growth promoting effect, and the results of practical tests were not good.

On the other hand, the hair restoration cosmetics of the present invention of Examples 6 to 8 show a high mouse hair growth promoting effect and a human hair growth promoting effect, and the results of practical tests are also good. The results clearly showed good results over the entire range. In addition, in the case of using the hair restoration cosmetics of any of the examples, inflammation in mice and humans, and other symptoms considered to be side effects do not appear, and the hair restoration cosmetics of the present invention may be excellent in safety. It was clear.

Examples 9 to 11 and Comparative Example 3 (oily hair tonic) In the raw material composition shown in Table 4, as the active ingredient BHPPO, as shown in Table 5, 1,5-bis (p-hydroxy-m-
(Methoxyphenyl) -1,4-pentadien-3-one (the same compound as in Examples 6 to 8) was blended to prepare an oily hair tonic, and the above-described tests were performed.

[0038]

[Table 4]

[0039]

[Table 5]

(1) Preparation method The components belonging to (A) described in Table 4 were dissolved by heating, and the components belonging to (C), which were separately and uniformly dissolved, were gradually added. And mixed with stirring.

(2) Properties Table 5 shows the results of various tests performed on each oily hair tonic. As shown in Table 5, Comparative Example 3 had a low mouse hair growth promoting effect and a low human hair growth promoting effect, and the results of practical tests were not good.

On the other hand, the hair restoration cosmetics of the present invention of Examples 9 to 11 show high mouse hair growth promoting effect and human hair growth promoting effect, and have good results in practical tests.
Clearly good results were obtained over all of the tests.
In addition, when using the hair restoration cosmetics of any of the examples,
It does not cause inflammation or other side effects in mice and humans, and is excellent in safety.

Examples 12 and 13 and Comparative Example 4 (Heart Tonic) In the raw material composition shown in Table 6, as shown in Table 7, the active ingredient BHPPO was 1,5-bis (p-hydroxyphenyl) -1,4- Pentadien-3-one (Formula 7) was blended to prepare a hair tonic, and the above-described tests were performed.

[0044]

Embedded image

[0045]

[Table 6]

[0046]

[Table 7]

(1) Preparation method The components belonging to (A) described in Table 6 were dissolved by heating, the components belonging to (C) dissolved separately and gradually added, and the components (B) were further added to obtain a uniform mixture. And mixed with stirring.

(2) Characteristics Table 7 shows the results of various tests for each hair tonic. As shown in Table 7, Comparative Example 4 had low mouse hair growth promoting effect and human hair growth promoting effect, and the results of the practical test were not good.

On the other hand, the hair restoration cosmetics of the present invention of Examples 12 and 13 show high mouse hair growth promoting effect and human hair growth promoting effect, and also have good results in practical tests. The results clearly showed good results over the entire range. In addition, in the case of using the hair restoration cosmetics of any of the examples, inflammation in mice and humans, and other symptoms considered to be side effects do not appear, and the hair restoration cosmetics of the present invention may be excellent in safety. It was clear.

[0050]

As described above, it is apparent that the present invention provides a hair restoration cosmetic having an effect of activating hair matrix cells and having an excellent hair-growth effect and an effect of preventing hair loss.

Claims (1)

[Claims] 1. A hair restoration cosmetic comprising at least one bis-hydroxyphenyl pentadiene-one compound represented by the following general structural formula 1. Embedded image (However, R ₁ represents H, CH ₃ , C ₂ H _5. Also, the OR ₁ group represents 1 to 3 substitutions on each aromatic ring.)