JPH10139635A - Hair tonic - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a hair tonic containing an α1 -receptor blocker, having hair- growing actions such as a hair-falling preventing action and a trichogenous action without producing a side effect such as tachycardia, excellent in safety and stability and useful in the fields of medicines, cosmetics, etc. SOLUTION: This hair tonic contains one or more α1 -receptor blockers selected from prazosin, tetrazocine, tiodazosin and their pharmaceutically acceptable salts preferably in an amount of 0.001-5wt.% (based on the whole weight of the hair tonic). The hair tonic preferably contains an ovarian follicle hormone such as estrone, vitamin E (derivative), etc., for the enhancement of a hair- growing stimulation effect in addiction to the α1 -receptor blocker.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hair restorer, and more particularly, to a hair restorer having an excellent hair loss-preventing effect such as an anti-hair loss effect and a hair growth effect, which is used in the fields of pharmaceuticals, quasi-drugs and cosmetics.

[0002]

BACKGROUND OF THE INVENTION Alopecia is caused by poor nutritional intake, decreased scalp physiological function due to excessive occurrence of dandruff, decreased hair metabolism in hair follicles and hair bulbs caused by decreased blood flow in the scalp subcutaneous tissue and peripheral blood vessels, and It is caused by various causes such as mental stress.

In order to treat and improve such alopecia, estrogen such as estrone, estradiol, ethinyl estradiol, vitamin E and its derivatives, assembly extract, garlic extract, carrot extract, aloe extract, cepharanthin, chloride Peripheral vascular blood flow promoters such as carpronium and minoxidil, pepper tincture, tincture tincture, ginger tincture, peppermint oil, l-
Topical stimulants such as menthol and camphor; keratolytics such as resorcin, salicylic acid and lactic acid; antiseborrheic agents such as pyridoxine and its derivatives; bactericides such as zinc pyrithione, benzalkonium chloride, benzethonium chloride, chlorhexidine and hinokitiol; Acid and its derivatives, placenta extract, biotin, hair root activator such as pentadecanoic acid glyceride, glycyrrhizic acid and its derivatives, β
Anti-inflammatory agents such as glycyrrhetinic acid, allantoin, azulene, ε-aminocaproic acid and hydrocortisone; vitamins such as vitamins A, B ₂ , B ₆ , B ₁₂ and D; and amino acids such as cysteine, serine, methionine, leucine and tryptophan. Many hair-growing and hair-growing components, such as hair, have been used.

Testosterone-5α which catalyzes the conversion of testosterone to active dihydrotestosterone mainly for the treatment and improvement of male pattern baldness.
Many that inhibit reductase activity have been screened. Known inhibitors of the enzyme include steroid substances such as progesterone and deoxycorticosterone, as well as extracts of various types of plants. Also, oxendrone, spironolactone, cyproterone acetate, and the like are said to inhibit dihydroxytestosterone from binding to its receptor.

[0005] However, some of the above-mentioned conventionally used hair-growth and hair-growth components and testosterone-5α-reductor inhibitors have side effects, so that the amount that can be incorporated is limited or the effect is insufficient. Many of them have problems such as poor stability in hair restorer formulations or difficulty in obtaining products of a certain quality.

On the other hand, compounds having an α-receptor blocking action, such as tolazoline, phentolamine, thymoxamine,
It has been reported that phenoxybenzamine and azapetin have a hair-growth effect (JP-A-55-49307).
However, it is known that such an α-receptor blocker induces release of norepinephrine as a side effect, and may cause side effects such as tachycardia due to stimulation of the heart β1-receptor.

[0007]

SUMMARY OF THE INVENTION An object of the present invention is to provide a hair restorer which is free from the above-mentioned side effects, has good safety, and can exhibit an excellent hair restore effect.

[0008]

In order to solve the above-mentioned problems, various studies have been made. As a result, an α1-receptor blocking agent having a selective blocking action on α1-receptor has an excellent hair-growth effect. Exerts its effect and does not induce the release of norepinephrine.
Without causing side effects such as tachycardia due to receptor stimulation,
The present inventors have found that a highly safe hair restorer can be obtained, and have completed the present invention.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention relates to a hair restorer containing an α1-receptor blocker as an active ingredient. Such α1-
The receptor blocking agent is represented by the formula (1)

Embedded image A prazosin represented by the formula (2)

Embedded image A tetrazocine represented by the formula (3)

Embedded image And pharmaceutically acceptable salts of these compounds, and compounds having derivatives of α1-receptor that are derivatives of these compounds. Among these compounds, prazosin hydrochloride is most preferred from the viewpoints of hair growth effect, safety and stability.

The amount of the α1-receptor blocking agent used in the present invention is 0.0001 to 10% by weight based on the total amount of the hair restorer.
Preferably it is 0.001 to 5% by weight.

In the hair restorer according to the present invention, estrogen such as estrone, estradiol, ethinyl estradiol, and vitamin E, in addition to the α1-receptor blocker as an active ingredient, are used to enhance the effect of promoting hair growth and hair growth. And its derivatives, assemblage extract, garlic extract, carrot extract, aloe extract, peripheral blood flow enhancers such as cepharanthin, carpronium chloride, minoxidil, capsicum tincture, cantarris tincture, ginger tincture, peppermint oil, l -Local stimulants such as menthol and camphor; keratolytics such as resorcin, salicylic acid and lactic acid; antiseborrheic agents such as pyridoxine and its derivatives; bactericides such as zinc pyrithione, benzalkonium chloride, benzethonium chloride, chlorhexidine and hinokitiol; Pantothenic acid and its induction , Placenta extract, biotin, hair root activating agent such as pentadecanoic acid glyceride, glycyrrhizic acid and its derivatives, beta-glycyrrhetinic acid, allantoin,
Anti-inflammatory agents such as azulene, ε-aminocaproic acid and hydrocortisone, vitamins such as vitamins A, B ₂ , B ₆ , B ₁₂ and D, and amino acids such as cysteine, serine, methionine, leucine and tryptophan are simultaneously incorporated. be able to. Further, steroid substances such as progesterone and deoxycorticosterone, bicycloheptenone derivatives, phenoxybutanoic acid derivatives, tocopherylquinone, tropolone derivatives, potassium bromate, cinnamic acid amide derivatives containing pentyl or neopentyl groups, and testosterone such as ubiquinone. 5α-reductase inhibitors, cyclooxygenase inhibitors such as unsaturated fatty acids, landic acid, etc., moray eel, mussels, mint, sage,
Plant extracts having a testosterone 5α-reductase inhibitory activity, such as thyme, perilla, peppermint, menthol, arnica, pearl mugwort, cuckoo thistle, and hops, can also be added at the same time.

Further, various ingredients generally used in cosmetics, for example, avocado oil, palm oil, peanut oil, rice bran oil, jojoba oil, orange roughy oil, macadamia nut oil within a range not impairing the effects of the present invention. Squalane, evening primrose oil, sesame oil, sunflower oil, safflower oil, carola oil, carnauba wax, paraffin wax, lanolin, diisostearyl malate, isostearyl alcohol, liquid paraffin and other oils, glycerin, diglycerin, Moisturizers such as polyglycerin, sorbit, polyethylene glycol, 1,3-butylene glycol, collagen, hyaluronic acid, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, 2-hydroxy -4-methoxybenzophenone-5-sulfone Benzophenone derivatives such as sodium oxalate; paraaminobenzoic acid derivatives such as paraaminobenzoic acid, ethyl paraaminobenzoate and octyl paradimethylaminobenzoate; 2-ethylhexyl paramethoxycinnamate; glyceryl mono-2-ethylhexanoate diparamethoxycinnamate; Methoxycinnamic acid derivatives, salicylic acid derivatives such as octyl salicylate and myristyl salicylate, urocanic acid, 4-tert-butyl-4'-methoxydibenzoylmethane, 2- (2'-hydroxy-5'-methylphenyl)
UV absorbers such as benzotriazole, natural plant polysaccharides such as guar gum, locust bean gum, carrageenan, quince seed, pectin, and mannan; microbial natural polysaccharides such as xanthan gum, dextran, curdlan, hyaluronic acid, gelatin, casein , Albumin, collagen and other animal polymers, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose and other semi-synthetic polymers, soluble starch, carboxymethyl starch, and methylstarch and other semi-synthetic polymers , Propylene glycol alginate,
Alginate-based semisynthetic polymers such as alginate, synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium polyacrylate, and polyethylene oxide; and water-soluble polymers such as bentonite, laponite, and colloidal alumina. Polymers, antioxidants such as dibutylhydroxytoluene, butylhydroxyanisole, and gallic acid esters, higher fatty acid soaps, alkyl sulfates, polyoxyethylene alkyl ether sulfates, acylmethyl taurine salts, alkyl ether phosphate salts, acyl Anionic surfactants such as amino acid salts, alkyltrimethylammonium chloride, dialkyldimethylammonium chloride,
Cationic surfactants such as benzalkonium chloride, amphoteric surfactants such as betaine alkyldimethylaminoacetate, betaine alkylamidodimethylaminoacetate, and 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine; Surfactants such as ethylene-type nonionic surfactants and alcohol ester-type nonionic surfactants, sequestering agents such as sodium ethylenediaminetetraacetate, sodium polyphosphate, citric acid, sodium metaphosphate, succinic acid, and gluconic acid; Can be blended.

The hair restorer may be in any form applicable to the scalp, such as liquid, milky, creamy and ointment.

[0014]

The effect of α1-receptor blocking agent on hair follicle cell proliferation was examined using cultured mouse hair follicle cells. Hair follicle cells isolated from neonatal mice were treated with Dulbec 10% fetal bovine serum.
The cells were seeded in a 96-well microplate at a cell concentration of 100,000 cells / well using o's medium. After culturing at 37 ° C. for 24 hours, the medium was replaced with an MCDB medium supplemented with an α1-receptor blocking agent. After culturing for 4 days, the cell activity was measured by the MTT reduction method. The system without the α1-receptor blocking agent was used as a control, and the value was taken as 100 to show the cell activity.

In the MTT reduction method, NADH generated by the action of a dehydrogenase present in the mitochondria of a cell on a substrate is used.
With the addition of MTT (2- (4,5-dimethyl-2-thia
zolyl) -3,5-diphenyltetrazolium bromide) is a measurement method using the ring opening of the tetrazolium ring. The blue pharmazan generated by the opening of the tetrazolium ring is measured by the absorbance at 560 nm to determine the cell viability. Ask.

[0016]

[Table 1]

As is clear from Table 1, α1-receptor blocking agents such as prazosin hydrochloride, tetrazosin, and thiodazosin were shown to significantly enhance the cell activity of cultured hair follicle cells derived from mice.

The hair growth promoting action of the α1-receptor blocking agent is
57 / Black mice. First, prazosin hydrochloride, tetrazosin, and thiodazosin were each dissolved in ethanol to prepare a concentration of 0.5% by weight. Next, the back of the C57 / Black mouse was shaved to a size of about 2 × 4 cm with a hair clipper, treated with a depilatory foam to completely remove hair, and after 24 hours, 0.1 ml of the above prepared solution was used once a day. It was applied continuously for 20 days. All hairs that grew on the last day of the test were extracted, and their total weight was measured. The test was performed with 10 animals per group, and the average values are shown in Table 2. At that time, a group to which only the solvent ethanol was applied was used as a control.

[0019]

[Table 2]

As is clear from Table 2, α1-receptor blockers such as prazosin hydrochloride, tetrazocine and thiodazosin were shown to have a superior hair growth promoting effect as compared with the control.

[0021]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The features of the present invention will be described in detail with reference to embodiments.

Examples 1 to 3 Hair tonics Hair tonics were prepared according to the recipe shown in Table 3 by a conventional method.

[0023]

[Table 3]

A use test was performed on Examples 1 to 3. At the same time, a hair tonic was prepared without blending the α1-receptor blocking agent, and was used as Comparative Example 1. The use test was conducted with a group of 20 male and female panelists who were worried about thinning hair. The group was used twice a day for 6 months consecutively, and the sensory evaluation was performed on the improvement of thinning hair and the presence or absence of irritation during use. Was. The results of the sensory evaluation were as follows: “Improved; 5
Points ”,“ Slightly improved; 4 points ”,“ No change; 3
Points ”,“ Slightly worse; 2 points ”,“ Worse; 1 point ”,
The stimulus at the time of use is “none; 5 points”, “somewhat not;
4 points "," neither way; 3 points ","somewhat;
Points were scored as "2 points" and "Yes; 1 point", and the average value of 20 persons was obtained. The results are shown in Table 4.

[0025]

[Table 4]

As is clear from Table 4, the group using the examples of the present invention showed a clear tendency to improve thinning hair. On the other hand, in Comparative Example 1 in which the α1-receptor blocking agent was not blended, none of the users had improved thinning hair. Regarding the irritant feeling during use, in each of Examples 1 to 3 and Comparative Example 1 of the present invention, no particularly problematic irritant feeling and discomfort were observed. In addition,
During the use period, no deterioration or deterioration of the preparation was observed in any of Examples 1 to 3, and even in a panel using each of the examples, a skin irritation reaction such as occurrence of erythema and edema, No skin sensitization reaction was observed.

[Example 4] Hair nourishing cream (1) Liquid paraffin 15.0 (% by weight) (2) Vaseline 15.0 (3) Beeswax 2.0 (4) Polyoxyethylene (50EO) hydrogenated castor oil 3 0.0 (5) Glycerin 5.0 (6) Carboxyvinyl polymer 0.1 (7) Xanthan gum 0.1 (8) Disodium ethylenediaminetetraacetate 0.1 (9) Purified water 58.15 (10) Sodium hydroxide 0.05 (11) Prazosin hydrochloride 0.5 (12) Ethanol 1.0 Production method: Heat and dissolve the oil phase of (1) to (3) to 80 ° C.
On the other hand, the aqueous phase components (4) to (9) were mixed and dissolved by heating.
And The oil phase is added to the water phase while stirring, and the mixture is uniformly emulsified by a homogenizer, and (10) is added. 30 ° C after cooling
(11) is dissolved in (12) and added.

Example 5 Hair Nourishing Gel (1) Carboxyvinyl polymer 0.7 (% by weight) (2) Polyvinylpyrrolidone 2.0 (3) Glycerin 5.0 (4) Sodium hydroxide 0.2 ( 5) Ethanol 10.0 (6) Disodium ethylenediaminetetraacetate 0.1 (7) Purified water 78.7 (8) Tetrazocine 0.3 (9) Ethanol 3.0 Production method: (1) to (3) and (3) Disperse in part of 7). (2), (4)
(6) was dissolved in the remainder of (7) and further dissolved in (9) (8)
Is added.

Example 6 Set lotion (1) Polyvinylpyrrolidone-vinyl acetate copolymer 5.0 (% by weight) (2) Methyl parahydroxybenzoate 0.1 (3) Fragrance 0.2 (4) Thiodazocine 0 0.4 (5) Ethanol 30.0 (6) Polyoxyethylene-modified silicone 0.5 (7) Glycerin 2.0 (8) Purified water 61.8 Production method: (1) to (4) are sequentially changed to (5) Add and dissolve. On the other hand (6)
The aqueous phases of (8) to (8) are mixed and dissolved, and added to the above solution and mixed to make it uniform.

Example 7 Hair Liquid (1) Ethanol 50.0 (% by weight) (2) Polyoxypropylene (40PO) butyl ether 20.0 (3) Polyoxyethylene (50EO) hydrogenated castor oil 1.0 ( 4) Methyl paraoxybenzoate 0.15 (5) Prazosin hydrochloride 0.5 (6) Fragrance 0.1 (7) Blue No. 1 (1% aqueous solution) 0.1 (8) Purified water 28.15 Production method: ( The components (2) to (8) are sequentially added and dissolved in 1) to make them uniform.

Example 8 Water Grease (1) Carboxyvinyl polymer 0.5 (% by weight) (2) Glycerin 50.0 (3) Purified water 38.6 (4) Polyoxyethylene (20EO) 0.2 Octyldodecyl ether (5) Sodium hydroxide 0.1 (6) Ethanol 10.0 (7) Fragrance 0.2 (8) Tetrazocine 0.4 Production method: (1) is dispersed in (2), and (4) is Add to the melted (3) and heat to dissolve and homogenize. After cooling, neutralize with component (5), dissolve (7) and (8) in (6) and add.

Example 9 Hair Foam (Undiluted Formulation) (1) Silicone Oil 5.0 (% by weight) (2) Polyoxyethylene (50EO) Hardened Castor Oil 1.0 (3) Dipropylene Glycol 7.0 (4) Cationized cellulose 3.0 (5) Purified water 68.35 (6) Ethanol 15.0 (7) Methyl parahydroxybenzoate 0.15 (8) Thiodazocin 0.5 (filling formulation) Stock solution 90.0 Liquefaction Petroleum gas 10.0 Production method: (1) is added to the melts of (2) and (3) and homogenized with a homogenizer. This is added while (4) is dissolved in (5), and then (7) and (8) are dissolved in (6), added and mixed to obtain a stock solution. For filling, a can is filled with a stock solution, and after mounting a valve, liquefied petroleum gas is filled.

Example 10 Hair Shampoo (1) Sodium salt of polyoxyethylene (3EO) lauryl sulfate 30.0 (wt%) ester (30 wt% aqueous solution) (2) Sodium salt of lauryl sulfate 10.0 (30 (3%) Coconut oil fatty acid diethanolamide 4.0 (4) Glycerin 1.0 (5) Methyl parahydroxybenzoate 0.2 (6) Disodium ethylenediaminetetraacetate 0.25 (7) Purified water 52. 85 (8) Ethanol 1.0 (9) Fragrance 0.2 (10) Prazosin hydrochloride 0.5 Manufacturing method: (7) is heated to 70 ° C., and (1) to (6) are added and uniformly dissolved. Cool and dissolve (9) and (10) in (8) and add.

Example 11 Hair rinse (1) Silicone oil 3.0 (% by weight) (2) Liquid paraffin 1.0 (3) Cetanol 1.5 (4) Stearyl alcohol 1.0 (5) Stearyl trimethyl chloride Ammonium 0.7 (6) Glycerin 3.0 (7) Methyl paraoxybenzoate 0.2 (8) Purified water 87.2 (9) Ethanol 2.0 (10) Tetrazocine 0.3 (11) Fragrance 0.1 Production method: The oil phase components (1) to (4) and the aqueous phase components (5) to (8) are mixed and dissolved, respectively, and heated to 70 ° C. The oil phase is added to the water phase to emulsify, and after cooling, (10) and (11) are dissolved in (9) and added.

[0035]

As described in detail above, the α1-receptor blocker has a strong hair-growth action,
It has good safety and excellent hair growth promoting effect.

Claims (2)

[Claims] 1. A hair restorer containing an α1-receptor blocker. 2. The hair restorer according to claim 1, wherein the α1-receptor blocker is one or more selected from prazosin, tetrazosin, thiodazosin and pharmaceutically acceptable salts thereof.