JP2512924B2 - Hair restorer - Google Patents

Description

TECHNICAL FIELD The present invention relates to a hair-growing agent mainly composed of pyridinecarboxylic acid 1-oxide having a remarkable hair-promoting action, which is useful in the fields of medicine and cosmetics. .

2. Description of the Related Art Conventional hair growth agents containing various medicinal components have been known. For example, a bactericidal agent, a keratolytic agent, a hormone agent, a vitamin agent, an amino acid and / or a vasodilator has been incorporated to remove hair. It is used for the prevention and treatment of diseases. Among these medicinal ingredients, for pyridinecarboxylic acid derivatives, benzyl nicotinate is used as a hair-growing agent for quasi-drugs [edited by the Japan Association of Official Protocols, Pharmaceutical Manufacturing Guidelines (1986 version), page 431. ]. Furthermore, vitamin E nicotinic acid ester is known as having a vasodilatory effect on peripheral blood and showing an advantageous effect on hair growth [see Japanese Patent Publication No. 47-47663]. Further, nicotinic acid is also used as a main component or one component of hair nourishing cosmetics [see JP-A-48-58149 and JP-B-56-32962]. However, there is no report that nicotinic acid 1-oxide, and further pyridinecarboxylic acid 1-oxide or a derivative thereof, has a hair growth promoting action.

Problems to be Solved by the Invention It is an object of the present invention to provide a composition having an excellent hair growth promoting action.

Means for Solving the Problems As a result of various searches for compounds having a hair growth promoting action, the present inventors have found that the compound represented by the general formula [I] described below exhibits an excellent hair growth promoting action. Thus, the present invention has been completed.

Action The present invention has the general formula [In the formula, X represents a carboxyl group, and n represents 1, 2 or 3. ] It is related with the hair restorer which uses the pyridine carboxylic acid 1-oxide derivative or its salt represented by these as an active ingredient.

The pyridinecarboxylic acid 1-oxide derivative used in the present invention is a conventionally known compound and is known in the art, for example, Eiji Ochiai, Aromatic Amine Oxides No. 1
Pages 9-26 (1967) Elsevier Publishing
It can be easily obtained by oxidizing the corresponding pyridinecarboxylic acid derivative on the market by the method described in the company (Elsevier Publishing Company), the method described in JP-B-56-23987 and the like.

Examples of the salt of the pyridinecarboxylic acid 1-oxide derivative which is the active ingredient of the hair restorer of the present invention include salts with alkali metals such as sodium or potassium, potassium,
Examples thereof include salts with alkaline earth metals such as barium and magnesium, and salts with organic amines such as methylamine, diethylamine, ethylamine, dimethylamine and triethylamine salts.

The hair restorer of the present invention can be used by transdermal administration or oral administration.

When the hair restorer of the present invention is prepared as a percutaneous preparation, a diluent, a cream base or the like is added to the pyridinecarboxylic acid 1-oxide derivative as an active ingredient to prepare a solution, a usual hair cosmetic such as a cream. It can be prepared in a suitable form, but a solution form is particularly preferable. This solution is usually
Methanol, dimethyl sulfoxide, ethanol,
It is easily prepared by dissolving the pyridinecarboxylic acid 1-oxide derivative or its salt, which is the active ingredient of the hair restorer of the present invention, in water, isopropanol, glycerin, propylene glycol or a mixture thereof. The content of the pyridinecarboxylic acid 1-oxide derivative, which is an active ingredient of the hair restorer of the present invention, is about 0.01 to about 5% by weight, preferably about 0.1 to about 3% by weight. In addition, other hair nourishing ingredients, known vitamin agents, scalp stimulants, pigments and fragrances used in hair cosmetics, or other auxiliary agents can also be added.

When the hair restorer of the present invention is used, for example, a solution or cream is added in an amount of about 0.02 to 0.1 ml per cm ² of the scalp.
Apply once or several times a day.

When the hair restorer of the present invention is prepared as an oral administration agent, for example, powders, granules, tablets, pills,
It can be adjusted to a solvent, a suspension, a capsule, or the like.
In this route of administration, the pyridinecarboxylic acid 1 of the present invention
The dose of the oxide derivative is 0.1 to 10 mg / day.
kg. When the hair restorer of the present invention is used, the dose can be adjusted according to the patient's weight, age, administration method, physical condition, symptoms, and the like.

Hereinafter, the hair growth promoting effect and safety of the hair restorer of the present invention will be described with reference to pharmacological test examples. The following compounds were used as test drugs.

Test reagent Compound A: 3-pyridinecarboxylic acid 1-oxide Compound B: 2,6-pyridinedicarboxylic acid 1-oxide Compound C: 2,4-pyridinedicarboxylic acid 1-oxide Test Example 1 Hair growth promoting action 6-week-old BDF The back of _one mouse (male) was shaved with a hair clipper and a shaver to make 10 mice per group. From the next day, the sample was applied to the mouse twice a day with a lotion containing 2% of the test drug.
Each 30 μ was applied continuously for 14 days. On the other hand, a lotion base was applied to the control group.

Evaluation of the hair growth promoting effect, the hair growth area of the shaving part is 0 to 20%,
It was divided into 5 stages of 20 to 40%, 40 to 60%, 60 to 80% and 80 to 100%, the hair growth score was determined to be 1 to 5, and the hair was observed daily by visual observation. Table 1 shows the observation results on the 13th day after application.
Shown in The lotion base was a mixture of dimethyl sulfoxide, glycerin and methanol (mixing ratio 12:
(5: 3 volume ratio) or a mixture thereof containing a trace amount of hydrochloric acid as needed.

Results As is clear from Table-1, the hair restorer of the present invention showed a hair growth promoting effect. At this time, no weight loss and skin irritation due to the application of the test drug were observed, and no abnormality was observed in other general conditions.

Test Example 2 Protein production accelerating action in cultured keratinocytes Keratinocytes were isolated from the epidermis of zero-day-old ICR mice, and primary culture was performed on a 12-well culture plate.
After 23 hours, the medium was changed to a medium containing the test drug, and 2 days later, the following evaluation was performed. The results are shown in Table-2. The vehicle used to add each test drug was propylene glycol,
A small amount of hydrochloric acid was added as needed to a mixed solvent of ethanol and distilled water (mixing ratio 5: 3: 2 volume ratio), and the final concentration was 1%. The final concentration of each test drug was 5 or 10 μg / ml.

The evaluation was performed using the amount of increased protein production by keratinocytes as an index.

Results As shown in Table 2, in the cultured keratinocytes derived from mouse epidermis, the active ingredient of the hair-growing agent of the present invention has the effect of significantly promoting the production of protein.

Test Example 3 Acute toxicity Five-week-old ICR mice (female) were injected with 0.1 ml of the test drug solution into the tail vein, and the 50% lethal dose (LD ₅₀ value) was measured. In addition,
The test drug was dissolved in 4N-NaOH, adjusted to pH 7.0, and used for the test. The results are shown in Table-3.

Test Example 4 Delayed Skin Reaction Test Example 1 in which the back of a 9-week-old ICR mouse (female) was shaved
2% test drug solution dissolved in lotion base used in
100 μ was applied. After the lapse of 7 days, the thickness of the ear was measured, and then 10 μ each of the lotion base solution of 3% test drug was applied to the front and back of both ears of the mouse. After 24 hours, ear thickness was measured.

As a result, Compound A and Compound C, which were tested as test drugs, have no effect of increasing the ear thickness, and thus Compound A and Compound C do not show skin irritation action or hapten-like antigen action.

Test Example 5 Inflammatory reaction 30 weeks of a test drug solution dissolved in 4N-NaOH and adjusted to pH 7.0 was injected subcutaneously into the footpad of a 6-week-old ICR mouse (female),
The thickness of the footpad was measured. As a result, Compound A and Compound C showed no change in the thickness of the foot pads at doses up to 1 mg / mouse, and neither of these test drugs showed inflammatory properties.

As is apparent from the above test examples, the hair restorer of the present invention has extremely low toxicity and does not have side effects such as skin irritation that may be feared when used as an external hair restorer. It has suitable conditions as an agent.

Examples Next, examples of the hair-growth agent according to the present invention will be shown.

Example 1 Hair Tonic 1. Ethanol 60 ml 2. Vegetable oil 0.5 g 3. Propylene glycol 5.0 g 4.3-Pyridinecarboxylic acid 1-oxide 5.0 g 5. Purified water is added to make 100 ml.

 The above ingredients are mixed and dissolved to obtain a product.

Example 2 1. Ethanol 50 ml 2. Vegetable oil 0.5 g 3. Propylene glycol 5.0 g 4. Sodium 3-pyridinecarboxylate 1-oxide
5.0g 5. Add purified water to make 100ml.

Example 3 Hair lotion 1. Stearic acid 5.0 g 2. Cetanol 0.5 g 3. Alacell 83  1.0g 4. Triethanolamine 0.4g 5. Glycerol 5.0g 6. Tocopherol acetate 0.01g 7. Capsicum tincture 3ml 8.2,6-Pyridinedicarboxylic acid 1-oxide 2.0g 9. Preservative, perfume, appropriate amount 10. Purified water added To 100 ml.

Among the above components, 1 to 3 are heated to 70 to 80 ° C. to melt,
To this, add 4 to 10 of the same temperature, cool with stirring and adjust.

Example 4 Hair shampoo 1. Sodium lauryl ether sulfate 20.0 g 2. Sodium lauryl sulfate 10.0 g 3. Lauryl sulfate diethanolamide 5.0 g 4. Propylene glycol 2.0 g 5. Assemblage extract 0.1 g 6.2,4-pyridinedicarboxylic acid 1-oxide 2.0g 7. Preservatives, dyes and flavors 8. Add purified water to make 100 ml.

 The above ingredients are mixed and dissolved to obtain a product.

Example 5 Hair Cream 1. Vaseline 2.5 g 2. Liquid paraffin 10.0 g 3. Cetostearyl alcohol 12.0 g 4. Polyoxyethylene sorbitin monostearate 7.0 g 5. Sorbitan monostearate 1.0 g 6. Propylene glycol 5.0 g 7.3 -Pyridinecarboxylic acid 1-oxide 2.0 g 8. Preservative, perfume appropriate amount 9. Purified water is added to make 100 g.

The oil layer of 1 to 5 and the aqueous layer of components 6 to 10 among the above components are respectively heated to 75 ° C., emulsified, and further cooled with stirring to obtain a product.

EFFECTS OF THE INVENTION Pyridinecarboxylic acid 1-oxide, which is an active ingredient of the hair restorer of the present invention, exhibits an excellent hair growth promoting action, and is therefore useful as a preventive or therapeutic agent for juvenile and macular alopecia.

Claims (8)

(57) [Claims] 1. A general formula [In the formula, X represents a carboxyl group, and n represents 1, 2 or 3. ] A hair restorer containing a pyridinecarboxylic acid 1-oxide derivative represented by the formula or a salt thereof as an active ingredient. 2. The hair restorer according to claim 1, which comprises 2-pyridinecarboxylic acid 1-oxide as an active ingredient. 3. The hair restorer according to claim 1, which comprises 3-pyridinecarboxylic acid 1-oxide as an active ingredient. 4. The hair restorer according to claim 1, which comprises 4-pyridinecarboxylic acid 1-oxide as an active ingredient. 5. A method according to claim 1, wherein 2,4-pyridinedicarboxylic acid 1-oxide is used as an active ingredient.
The hair restorer according to the item. 6. A method according to claim 1, characterized in that 2,5-pyridinedicarboxylic acid 1-oxide is used as an active ingredient.
The hair restorer according to the item. 7. A method according to claim 1, wherein 2,6-pyridinedicarboxylic acid 1-oxide is used as an active ingredient.
The hair restorer according to the item. 8. A method according to claim 1, characterized in that 3,5-pyridinedicarboxylic acid 1-oxide is used as an active ingredient.
The hair restorer according to the item.