JP2818028B2 - Hair restorer - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a novel hair restorer, and more particularly, to a hair restorer containing an amine oxide and a compound having a calmodulin inhibitory action and / or a compound having a calcium antagonism action.

BACKGROUND ART Conventionally, baldness and alopecia have the following intent: (1) activation of male hormones in organs such as hair roots and sebaceous glands, (2) decrease in blood flow to hair follicles, (3) excessive secretion of sebum, and peroxidation. Abnormalities of the scalp due to production of products, proliferation of bacteria, etc., (4) genetic factors, (5) neurosis due to stress, etc., (6) secondary diseases, (7) aging, etc. .

For this reason, a compound having an action of removing or reducing the above-mentioned causes is generally added to a conventional hair restorer. For example, a compound having an effect of inhibiting androgen activation or a compound having an effect of increasing blood flow to a hair follicle is included.

However, the mechanism of hair loss and hair growth is extremely complicated, and simply inhibiting the activation of male sex hormones or increasing the blood flow of hair follicles cannot sufficiently prevent baldness and hair loss.

DISCLOSURE OF THE INVENTION Accordingly, it is an object of the present invention to provide a hair restorer which overcomes the above-mentioned problems of the conventional hair restorer and has excellent hair loss preventing and hair restorer action.

Other objects and advantages of the present invention will be apparent from the following description.

According to the present invention, (i) amine oxide and (ii)
Provided is a hair restorer comprising at least one compound selected from a compound having a calmodulin inhibitory action and a compound having a calcium antagonistic action.

BEST MODE FOR CARRYING OUT THE INVENTION The present inventors have searched for a substance having an effective action on hair loss, and have searched for a substance having an excellent hair-growth action. It has been found that it has an effect of preventing hair loss and hair growth. The hair restorer based on this invention is described in the specification of Japanese Patent Application No. 63-6233. The present inventors have further studied the above amine oxide, and when combined with a specific substance, prevent hair loss,
They found that the effect of hair growth was enhanced and completed the present invention.

The following are examples of the amine oxide used in the present invention.

(1) Dimethylalkylamine oxide represented by the general formula (A) (In the formula, R ¹ represents a linear or branched alkyl group or alkenyl group having 8 to 24 carbon atoms.) Specific examples thereof include dimethyllaurylamine oxide and dimethylstearylamine oxide.

(2) Methyldialkylamine oxide represented by the general formula (B) (In the formula, R ² and R ³ represent a straight-chain or branched alkyl group or alkenyl group having 6 to 18 carbon atoms.) Specific examples include didecylamine oxide and didodecylamine oxide.

(3) Dihydroxyethylalkylamine oxide represented by the general formula (C) (In the formula, R ⁴ represents a linear or branched alkyl group or alkenyl group having 8 to 24 carbon atoms.) Specific examples include dihydroxyethyllaurylamine oxide.

(4) dimethyl alkyl polyoxyethylene amine oxide represented by the general formula (D) (In the formula, R ⁵ represents a linear or branched alkyl group or alkenyl group having 8 to 24 carbon atoms, and n represents a positive number of 1 to 5.) Specific examples include dimethylallylethoxyamine oxide and the like. Is mentioned.

(5) Amidopropylalkyldimethylamine oxide represented by the general formula (E) (In the formula, R ⁶ represents a linear or branched alkyl group or alkenyl group having 8 to 24 carbon atoms.) Specific examples include dimethyllaurylamidopropylamine oxide.

One or more of the amine oxides of the above general formulas (A) to (E) may be mentioned.

And the "compound having a calmodulin inhibitory effect" used in the present invention, that is, a calmodulin inhibitor,
It refers to any compound that binds to calmodulin, selectively inhibits the enzyme activated by calcium in calmodulin, or can promote hair growth in mammals.

Specifically, phenothiazine, thioxanthin, butyrophenone, diphenylbutylamine, dibenzodiazepine, benzodiazepine, dibenzazepine, naphthalenesulfonamide, N- (6-aminohexyl) -5-chloro-1-naphthalenesulfonamide, trifluoperazine, chlorpromazine, Pleniramine, butaclamol, amitributyrin, felodipine, vinplastin, vincristine, fluphenazine, pimozide, medazepam, protriptyline, (1- [bis (p-chlorophenyl) methyl] -3- [2,4-dichloro-β
(2,4-dichlorobenzyloxy) phenethyl] imidazolinium chloride, flupentixol, chlorprothixene, haloperidol, chlordiazepoxide,
Examples include tetracaine, lidocaine, zipcaine, desipramine, clozapine, purmetazine, phentolamine, imipramine, benperidol, and the like.

The calcium antagonist used in the present invention is a calcium channel having a membrane potential mainly in vivo, that is, a channel which operates by depolarization of a cell membrane to allow extracellular calcium ions to flow into cells and intracellular calcium. It means any compound that can suppress the movement of calcium ions from the storage site and promote hair growth in mammals.

 Specifically, the following compounds are included.

(1) 1,4-dihydropyridine derivative Preferably, there are nifedipine, nicardipine, nildipine, nimodipine, nisoldipine, nitrendipine, milvadipine, dazodipine, felodipine and the like.

(2) N-methyl-N-homoveratramine derivative Derivatives preferably include verapamil, galopamil, and tiapamil.

(3) Benzothiazepine derivatives Diltiazem and the like are preferable.

(4) Piperazine derivatives Preferably, there are cinnarizine, lidofrazine, flunarizine and the like.

(5) Diphenylpropyramine derivative Preferable examples include breniramine, terodiline, fendiline and the like.

(6) Benzothiazole phosphonate derivative preferably diethyl-4- (benzothiazole-2-
Il) Benzylphosphonate / hostedil and the like.

(7) Bepridyl derivative Preferably, there is bepridil and the like.

(8) Perhexiline derivatives Perhexiline and the like are preferable.

(9) Others 3,4,5-trimethoxybenzoic acid 8-
(Diethylamino) octyl ester and the like.

In addition, the hair restorer of the present invention may be pharmaceutically acceptable in addition to the amine oxide and the essential components of a calmodulin inhibitor and / or a calcium antagonist as needed, within a range that does not impair the effects of the present invention. Possible additives and other agents can be added and used in the form of a mixture.

Examples of the additive include hinokitiol, hexachlorophen, phenol, benzalkonium chloride,
Antibacterial agents such as cetylpyridinium chloride, undecylenic acid, trichlorocarbanilide and bionol, derivatives such as glycyrrhizic acid and its ammonium salt, anti-inflammatory or refreshing agents such as allantoin and menthol, salicylic acid, zinc and its compounds, lactic acid and its alkyl esters Such as olive oil, macadamia nut oil, animal and vegetable oils such as squalane, hydrocarbon oils such as liquid paraffin, ester oils such as isopropyl myristate, cetyl isooctanoate, 2-ethylhexyl palmitate, and waxes such as beeswax , Higher fatty acids, oils such as higher alcohols, water, derivatives of lactic acid and ethyl esters thereof, polyhydric alcohols such as polyethylene glycol, glycerin and sorbitol, lower alcohols such as ethanol , Mucopolysaccharides, pyrrolidone humectant such as carboxylic acid salts, surface active agents, perfumes, antioxidants, ultraviolet absorbers, and the like can be illustrated dyes, used by mixing them one or two or more.

The dosage form of the hair restorer of the present invention may be in any form as long as it can be used externally, and includes, for example, external preparations such as lotions, liniments, and emulsions, semi-solid preparations such as creams, ointments, pastas, jellies, and sprays. be able to.

The hair restorer of the present invention contains an amine oxide as an active ingredient.
The compound having a calmodulin inhibitory action and / or a compound having a calcium antagonizing action is compounded in the range of 0.0001 to 20% by weight.
% By weight, preferably 0.0001 to 5% by weight. The mixing ratio of the amine oxide and the calmodulin inhibitor and / or calcium antagonist is not particularly limited, but is preferably 10,000: 1 to 1: 10,000, more preferably 10: 1 by weight.
A range of 00: 1 to 1: 1000 is desirable.

The hair restorer of the present invention is obtained by transdermal administration, which is applied or sprayed directly on the skin.

In addition, the dosage of the hair restorer of the present invention can not be clearly defined by age, individual differences, medical conditions, etc., but in general, when targeting a human, the body weight is 1 kg and 0.0001 to 1 g per day, preferably 0.001 to 0.1 g. It is. The above-mentioned amounts can be administered once or twice to four times a day.

(Examples) Hereinafter, the method for formulating the hair restorer according to the present invention and the hair restore effect will be specifically described with reference to examples, but it goes without saying that the present invention is not limited to these examples. % In the examples represents% by weight.

Hair growth effect test example (1) Mouse hair growth test (1) In order to examine the hair growth effect of the present invention, a mouse hair growth test was performed. That is, the back of a resting C3H / HeNCrj male mouse was shaved, and the six kinds of samples shown in Table 1 were given once a day.
Each 0.1 ml was applied. The effect was determined by calculating the hair growth area ratio based on photography.

Results Table 2 shows the hair growth area ratio and the judgment 2 weeks after application.

(2) Hair Growth Test Using Mice (Part 2) The backs of C3H / HeNCrj male mice in resting period were shaved with clippers, and 0.1 ml of the six samples shown in Table 3 was applied once a day. The effect was determined from the hair growth area ratio (%) based on the photograph taken 4 weeks after the application. Table 3 shows the results.

(3) Hair Growth Test Using Mice (Part 3) The backs of C3H / HeNCrj male mice in resting period were shaved with clippers, and 0.1 ml of each of the seven samples shown in Table 4 was applied once a day. The effect was determined by the hair growth area ratio (%) based on photography on the 31st day after the start of application. Table 4 shows the results.

(4) Hair Growth Test with Mice (Part 4) The back of a resting C3H / HeNCrj strain male mouse was shaved with a hair clipper, and 0.1 ml of each of the four samples shown in Table 5 was applied once a day. The effect was determined on the 52th day from the start of application by the hair growth area ratio (%) based on photography. Table 5 shows the results.

As is clear from the above results, the hair restorer containing amine oxide, a compound having a calmoduri inhibitory action and / or a compound having a calcium antagonistic action has a remarkable effect, and the hair restorer according to the present invention has an extremely excellent hair restorer effect. Have.

Example 1: Lotion 95% ethanol 80.0 Trifluoperazine 0.01 Dimethyl lauryl amine oxide 0.2 Sodium lauryl sulfate 0.06 Ethylene oxide (40 mol) adduct of hydrogenated castor oil 0.5 Purified water 19.23 Flavors and dyes Appropriate amount of 95% ethanol, Trifluoperazine, Dissolve the ethylene oxide (40 mol) adduct of hydrogenated castor oil and perfume, then add purified water, add dimethyl lauryl amine oxide, sodium lauryl sulfate and pigment,
The mixture was stirred and dissolved to obtain a transparent liquid lotion.

Example 2: Emulsion (Phase A) Whale wax 0.5 Cetanol 2.0 Vaseline 5.0 Squalane 10.0 Polyoxyethylene (10 mol) monostearate 2.0 Sorbitan monooleate 1.0 Naphthalene sulfonamide 0.1 Dimethyl stearylamine oxide 1.0 (Phase B) Glycerin 10.0 Purification Water 68.2 Flavors, dyes and preservatives qs Heat and melt phase A and phase B, respectively, and keep at 80 ° C. Both phases were mixed and emulsified and cooled to room temperature with stirring to obtain an emulsion.

Example 3: Cream (Phase A) Liquid paraffin 5.0 Cetostearyl alcohol 5.5 Vaseline 5.5 Glycerin monostearate 3.0 Polyoxyethylene (20 mol) 2-octyldodecyl ether 3.0 Propyl paraben 0.3 (B phase) Fluphenazine 0.001 Dimethylcetylamine oxide 10.0 Glycerin 7.0 Dipropylene glycol 20.0 Polyethylene glycol 4000 5.0 Sodium hexametaphosphate 0.005 Purified water Appropriate amount Heat and melt phase A and keep it at 70 ° C. The phase B was added to the phase A and stirred, and the obtained emulsion was cooled to obtain a cream.

Example 4: Emulsion Hair Restoration (Phase A) Squalane 9.0 Cetanol 2.0 Vaseline 5.0 Sorbitan Monooleate 1.0 Pleniramine 0.1 Dimethylstearylamine Oxide 1.0 Polyoxyethylene (10 mol) Monostearatetone 1.5 (B Phase) Glycerin 12.0 Purified Water 68.4 A phase and B phase were each heated and dissolved, and both phases were mixed and emulsified with a homomixer to obtain an emulsion hair restorer.

Example 5: Lotion 95% ethanol 80.0 Trifluoperazine 0.01 Didecylamine oxide 0.2 Sodium lauryl sulfate 0.06 Ethylene oxide (40 mol) adduct of hydrogenated castor oil 0.5 Purified water 19.23 Flavors and dyes Appropriate amount of 95% ethanol in trifluoperazine Then, an ethylene oxide (40 mol) adduct of hydrogenated castor oil and a fragrance were dissolved, then purified water was added, and then didecylamine oxide, sodium lauryl sulfate and a dye were added, and the mixture was stirred and dissolved to obtain a clear liquid lotion. .

Example 6: Emulsion (phase A) Whale wax 0.5 Cetanol 2.0 Vaseline 5.0 Squalane 10.0 Polyoxyethylene (10 mol) monostearate 2.0 Sorbitan monooleate 1.0 Didodecylamine oxide 0.1 Naphthalene sulfonamide 0.5 Dimethyl stearylamine oxide 1.0 Nifedipine 0.1 Lidocaine 0.001 (B phase) Glycerin 10.0 Purified water 68.2 Flavors, pigments and preservatives Appropriate amount Heat and melt phase A and B respectively, and keep at 80 ℃ Both phases were mixed and emulsified and cooled to room temperature with stirring to obtain an emulsion.

Example 7: Cream (Phase A) Liquid paraffin 5.0 Cetostearyl alcohol 5.5 Vaseline 5.5 Glycerin monostearate 3.0 Polyoxyethylene (20 mol) 2-octyldodecyl ether 3.0 Propyl paraben 0.3 (Phase B) Fluphenazine 5.0 Dimethylcetylamine oxide 0.05 Glycerin 7.0 Dilopylene glycol 20.0 Polyethylene glycol 4000 5.0 Sodium hexametaphosphate 0.005 Purified water Appropriate amount Heat and melt phase A and keep it at 70 ° C. The phase B was added to the phase A and stirred, and the obtained emulsion was cooled to obtain a cream.

Example 8: Emulsion hair restoration (phase A) squalane 9.0 cetanol 2.0 petrolatum 5.0 sorbitan monooleate 1.0 diltiazem 0.6 cinnarizine 0.3 dihydroxyethyl laurylamine oxide 0.0004 polyoxyethylene (10 mol) monostearate 1.5 (phase B) glycerin 12.0 purification Water 68.4 A phase and B phase were each heated and dissolved, and both phases were mixed and emulsified with a homomixer to obtain an emulsion hair restorer.

Example 9: lotion 95% ethanol 80.0 phenothiazine 0.0005 diazepam 0.0005 dimethyl lauryl ethoxyamine oxide 1.0 sodium lauryl sulfate 0.06 ethylenoxide (40 mol) adduct of hydrogenated castor oil 0.5 purified water 19.23 perfume and dye Dissolve diazepam, ethylene oxide (40 mol) adduct of hydrogenated castor oil and perfume, then add purified water, add dimethyl lauryl ethoxyamine oxide, sodium lauryl sulfate and pigment, stir and dissolve, and form a clear liquid lotion. Obtained.

Example 10: Emulsion (phase A) Whale wax 0.5 Cetanol 2.0 Vaseline 5.0 Squalane 10.0 Polyoxyethylene (10 mol) monostearate 2.0 Sorbitan monooleate 1.0 Dimethyloctylamine oxide 0.1 Naphthalene sulfonamide 0.1 Dimethyl stearylamine oxide 0.1 Nifedipine 0.1 (Phase B) Glycerin 10.0 Purified water 68.2 Flavors, pigments and preservatives Appropriate amount Heat phase A and phase B respectively to melt and keep at 80 ° C. Both phases were mixed and emulsified and cooled to room temperature with stirring to obtain an emulsion.

Example 11: Emulsion hair restoration (phase A) squalane 9.0 cetanol 2.0 petrolatum 5.0 sorbitan monooleate 1.0 TMB-8 [3,4,5-trimethoxybenzoic acid 8- (diethylamino) octyl ester] 0.1 dimethyl stearyl amide oxide 1.0 Polyoxyethylene (10 mol) monostearate 1.5 (B phase) Glycerin 12.0 Purified water 68.4 A phase and B phase were each heated and dissolved, and both phases were mixed and emulsified with a homomixer to obtain an emulsion hair restorer.

INDUSTRIAL APPLICABILITY The hair nourishing agent of the present invention has much better hair nourishing by combining an amine oxide with a compound having a calmodulin inhibitory action and / or a compound having a calcium antagonism action, as compared with the case of using each alone. It is a hair restorer.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-1-238515 (JP, A) WO 89/2731 (WO, A1) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61K 7/00-7/50

Claims (7)

(57) [Claims] 1. A hair restorer comprising (i) an amine oxide and (ii) at least one compound selected from compounds having a calmodulin inhibitory action and / or a compound having a calcium antagonistic action. 2. An amine oxide represented by the following general formula (A):
The hair restorer according to claim 1, which is at least one of the amine oxides (B), (C) and (D). (In the formula, R ¹ represents a linear or branched alkyl group or alkenyl group having 8 to 24 carbon atoms.) (In the formula, R ² and R ³ represent a linear or branched alkyl group or alkenyl group having 6 to 18 carbon atoms.) (In the formula, R ⁴ represents a linear or branched alkyl group or alkenyl group having 8 to 24 carbon atoms.) (In the formula, R ⁵ represents a linear or branched alkyl group or alkenyl group having 8 to 24 carbon atoms, and n represents a positive number of 1 to 5.) (In the formula, R ⁶ represents a linear or branched alkyl group or alkenyl group having 8 to 24 carbon atoms.) 3. A compound having a calmodulin inhibitory action, wherein the compound is phenothiazine, thioxanthin, butyrophenone, diphenylbutylamine, dibenzodiazepine, benzodiazepine, dibenzazepine, naphthalenesulfonamide, N- (6-aminohexyl) -5-chloro-1-naphthalenesulfonamide. , Trifluoperazine, Chlorpromazine, Pleniramine, Butaclmol, Amitributyrin, Felodipine, Vinplastin, Vincristine, Flufenazine, Pimozide, Medazepam, Protriptyline, 1- [Bis (p-chlorophenyl) methyl] -3- [2,4 -Dichloro-β (2,4-dichlorobenzyloxy) phenethyl] imidazolinium chloride, flupentixol, chlorprothixene, haloperidol, chlordia Pokishido, tetracaine, lidocaine, Jipukain, desipramine, clozapine, Purumetajin, phentolamine, imipramine, and tonic scope described first of claims is at least one compound selected from the group consisting of benperidol. (4) a compound having a calcium antagonistic action:
Claims which are selected from 4-dihydropyridine derivatives, N-methyl-N-homoverratilamine derivatives, benzothiazepine derivatives, piperazine derivatives, diphenylpropyramine derivatives, benzothiazole phosphonate derivatives, bepridyl derivatives and perhexiline derivatives. The hair restorer according to claim 1. 5. The hair restorer has an amine oxide content of 0.0001.
The hair restorer according to claim 1, wherein the amount is from 20 to 20% by weight. 6. The hair restorer according to claim 1, wherein the content of the compound having a calmodulin inhibitory action and / or the compound having a calcium antagonistic action in the hair restorer is 0.00001 to 10% by weight. 7. The weight ratio of the amine oxide in the hair restorer to the compound having a calmodulin inhibitory action and / or the compound having a calcium antagonistic action is 10,000: 1 to 1: 100 by weight.
2. The hair restorer according to claim 1, which is 00.