LU87070A1 - COMBINATION OF PYRIMIDINE DERIVATIVES AND AGENTS FOR INDUCING AND STIMULATING HAIR GROWTH AND REDUCING FALLING - Google Patents

Abstract

Combination intended for inducing and stimulating hair growth and for reducing hair loss, which comprises: (a) a component (A) containing, in a physiologically acceptable medium, at least one antibacterial agent chosen from antibiotics of the family of macrolides, pyranosides and also tetracylines; and (b) a component (B) containing, in a physiologically acceptable medium, at least one pyrimidine derivative corresponding to the formula: <IMAGE> in which R1 denotes a group <IMAGE> in which R3 and R4 may be chosen from hydrogen and an alkyl, alkenyl, alkylaryl or cycloalkyl group, R3 and R4 can also form a heterocycle with the nitrogen atom to which they are linked, optionally substituted; the group R2 is chosen from a hydrogen atom and an alkyl, alkenyl, alkylalkoxy, cycloalkyl, aryl, alkylaryl, arylalkyl, alkylarylalkyl, alkoxyarylalkyl or haloarylalkyl group; the components (A) and (B) forming part of one and the same composition or being intended for use separately, either simultaneously or successively or separated by an interval of time, on the scalp or the hair.

Description

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Association of pyrimidine derivatives and antibacterial agents to induce and stimulate hair growth and reduce hair loss.

The invention relates to the combination of pyrimidine derivatives and certain antibacterial agents for simultaneous, successive or time-delayed use with a view to inducing and stimulating hair growth and reducing hair loss.

10 Man has a capital of 100,000 to 150,000 hairs and it is normal to lose 50 to 100 hairs daily. The maintenance of this capital results essentially from the fact that the life of a hair is subjected to a hair cycle during which the hair is formed, grows and falls before being replaced by a new hair which appears in the same follicle.

We observe, during a hair cycle, successively three phases, namely: the anagen phase, the catagen phase and the telogen phase.

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During the first phase, called anagen, the hair goes through a period of active growth associated with intense metabolic activity in the bulb.

5 The second phase, called catagen, is transient and is marked by a slowdown in mitotic activities. During this phase, the hair undergoes an involution, the follicle atrophies and its dermal implantation appears higher and higher.

The terminal phase, called telogen, corresponds to a period of rest of the follicle and the hair ends up falling, pushed by an incipient anagen hair.

This permanent physical renewal process undergoes a natural evolution during aging, the hair becomes thinner, its cycles shorter.

Alopecia occurs when this process of physical renewal is accelerated or disturbed, that is to say that the growth phases are shortened, the passage of the hair into the telogen phase is earlier and the hair falls in greater numbers. Successive growth cycles result in thinner and shorter and shorter hair, gradually transforming into an unpigmented down. This phenomenon can lead to baldness.

The hair cycle is dependent on many factors that can lead to more or less pronounced alopecia. Among these factors, mention may be made of food, endocrine and nervous factors; etc.

The variation in the hair in the different phases is determined by means of the trichogram and in particular the photo-trichogram, which makes it possible, in particular, to determine the number of hairs in the anagen phase relative to the number of hairs in the telogen phase.

For many years, research has been carried out in the cosmetic or pharmaceutical industry on compositions which make it possible to suppress or reduce the effect of alopecia, and in particular to induce or stimulate hair growth or reduce hair loss.

With this in mind, 10 compounds have already been proposed such as amino-β 1,2-dihydro-1,2-hydroxy-2-imino-4 piperidino-pyrimidine and its derivatives, in particular "Minoxidil", such compounds are described, in particular, in US patent 4,139,619.

The Applicant has discovered that by combining an antibacterial agent chosen from antibiotics of the macrolide family, pyranosides, as well as tetracycline with a pyrimidine derivative, it was surprisingly possible to obtain greater efficacy than with previously known compositions containing only pyrimidine derivatives.

This result is particularly surprising when it is known that the antibiotics in question are not known to have an effect on hair growth or on their action on the braking of hair loss.

This efficiency is reflected, in particular, by an activity greater than the same concentration, determined in particular by a phototrichogram, by a faster action or by a use of the pyrimidine derivative at a lower concentration,

This effect has been observed, not only for compositions simultaneously containing the pyrimidine derivative and the antibiotics mentioned above, but also when they were used in separate steps.

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4 The subject of the invention is therefore a combination of pyrimidine derivatives and antibacterial agents chosen from antibiotics of the family of macrolides, pyranosides and tetracyclines.

Another subject of the invention consists of the compositions containing these agents.

Other objects of the invention will appear on reading the description and the examples which follow.

The association according to the invention is essentially characterized in that it comprises; a / a component (A) containing, in a physiologically acceptable medium, an antibacterial agent chosen from macrolides. pyranosides and tetracyclines; b / a component (B) containing in a physiologically acceptable medium a pyrimidine derivative corresponding to the formula:

20 OH

H2N N NE

Y T u)

R? I .N

25 R1

in which Ri denotes a group -N

^ R4 in which R3 and R4 can be chosen from hydrogen, an alkyl, alkenyl, alkylaryl or cycloalkyl group, R3 and R4 can also form a heterocycle with the nitrogen atom to which they are linked, chosen from aziridinyl groups , azetidinyl, pyrrolidinyl, p.peridinyl, hexahydroazepinyl, 22 heptamethyleneimine, octamethyleneimine, morpholine and

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5 alkyl-4 piperazidinyl, the heterocyclic groups being able to be substituted on the carbon atoms by one to three lower alkyl, hydroxy or alkoxy groups; the group R2 is chosen from a hydrogen atom, an alkyl, alkenyl, alkylalkoxy, cycloalkyl, aryl, alkylaryl, arylalkyl, alkylaryl-alkyl, alkoxyarylalkyl or haloarylalkyl group, as well as the physiologically acceptable acid addition salts, components (A) and (B) forming part of the same composition and being intended to be used separately, either simultaneously, or successively or staggered in time, in order to induce and stimulate hair growth and decrease their fall.

For the compounds of formula (I), the alkyl or alkoxy group preferably denotes a group having 1 to 4 carbon atoms; the alkenyl group preferably denotes a group · having 2 to 5 carbon atoms; the aryl group preferably denotes a phenyl group and the cycloalkyl group preferably denotes a group having 4 to 6 carbon atoms.

The particularly preferred compounds of formula (I) are chosen from the compounds in which R 2 denotes hydrogen and R 1 denotes a group: in which R 3 and R 4 form a piperidinyl ring, as well as their salts such as, for example, sulfate.

Among these compounds, a particularly preferred compound is constituted by 6-amino-1,2-dihydro-1,2-hydroxy-2-imino-piperidino-4 pyrimidine, also called "Minoxidil".

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The antibacterial agents of the macrolide family are more particularly chosen from erythromycin and its derivatives, and in particular erythromycin itself as well as estolate, ethylcarbonate, ethylsuccinate, glucoheptonate, lactobionate, propionyl laurylsulfate, propionate, stearate, linoleate, and mono-enic, bi- or tri-enic esters of erythromycin, as well as all-trans and 13-cis retinoic acid esters of erythromycin A, and their pharmaceutically acceptable salts as described more particularly in French patent application No. 86.06528 of the applicant, and in French patent 2,582,000.

The 2 ′ retinoic esters of erythromycin are represented more particularly by the formula: 0 ,, CH3 20 hVx> oh \ y0H ^ ch3 H3C "'j pCH3 R0V | N \ CH3 ÇH2 1) H3C-j / (II ) 25 “3 I ^“ 3 jf p och3

CH-, I

J ______________ ° R '30 R3' in which R represents the all-trans retinoyl radical or the 13-cis retinoyl radical, and R 'denotes H. The retinoyl radical having the formula: »> 7 (II!) I (z) 5

These different retinoic esters can be prepared according to different esterification processes and preferably in an anhydrous organic solvent medium, in particular in tetrahydrofuran alone or in mixture with another organic solvent such as pyridine, by reacting an excess of carbon dioxide mixed all-trans or 13-cis retinoic acids (prepared in situ, for example from ethyl chloroformate and all-trans or 13-cis acid) with erythromycin A, in the form of the base, in the presence 15, of an organic or mineral base such as pyridine and / or sodium hydrogencarbonate.

Other erythromycin A derivatives are those represented by formula (II) above, in which: R or R ′ represents a linear C18 bi- or tri-enic acyl radical, of all-cis stereochemical configuration ( Z) and R 'or R remaining represents a hydrogen atom.

According to a preferred embodiment, R or 25 ′ represents in these compounds the following radicals: Z-9, Z-12-octadecadienoyl or linoleoyl Z-9, Z-12, Z-15-octadecatrienoyl or -linolénoyl, and Z -6, Z-9, Z-12-octadecatrienoyl or -linolénoyl.

Mention may be made more particularly of O-linoleoyl-21 erythromycin A, 1 O-linoleoyl-4 "erythromycin A and O- ^ linoleoyl-4" erythromycin A.

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The antibacterial agents of the macrolide family are also chosen from spiramycin and its derivatives such as, for example, di- or triacetate, 11oleandomycin or its hydrochloride, as well as Roxytromycin, Josamycin and their derivatives.

The pyranosides are chosen more particularly from clindamycin and its derivatives, such as the hydrochloride, palmitate and phosphate, lincomycin and its derivatives, such as the hydrochloride. Other clindamycin or lincomycin derivatives are the lincomycin and clindamycin retinoates and their pharmaceutically acceptable salts as described more particularly in French patent application No. 86.06528 of the applicant, represented by the formulas:

Pa3 f3 V'Xr P3 Ks \ f f3 20 (o3S7 tOÇE \ j3H? Jy "| 1

Ky-fcoEH - “a Γ 1 cosa —CH

E ° l-0 * \ 0R ü / iCHß

a Qu H OH

(IV) (V) in which S represents the retinoyl radical of formula (III) above.

The esters are prepared as indicated above for erythromycin retinoates.

Another preparation process consists in using imidazolides of retinoic acids in lincomycin and clindamycin in a solvent.

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9 anhydrous such as Ν, Ν-dimethylformamide, in the presence of a base such as sodium or potassium tertioutylate. According to this latter process, the ester, in position 7 of lincomycin is obtained mainly with 5 of the esters in positions 2, 3 and 4. A mixture of monoesters in positions 2, 3 and 4 of the clindamycin.

The tetracycline derivatives are more particularly chosen from tetracycline and its derivatives, such as the hydrochloride, N- (n-dodecyl) sulfamate, guaïcolglycolate, guaïcolsulfonate, laurylsulfate, metaphosphate, tetracyclinephosphate complex, complex of tartrate, phenoxymethylpenicillinate, timolsulfonate, trimethoxybenzoate trihydrate.

Components (A) and (B) as well as the composition containing them in one embodiment, can be in various forms usually used for topical application, and more particularly in the form of an optionally thickened lotion, gel, emulsion, of foam possibly conditioned in aerosol, spray, stick.

The physiologically acceptable medium can consist of water, a mixture of water and a solvent or a mixture of solvents, the solvents being chosen from organic solvents, acceptable from the cosmetic or pharmaceutical point of view, and chosen more particularly among the lower C1-C4 alcohols such as ethyl alcohol, isopropyl alcohol, tert-butyl alcohol, alkylene glycols, alkylene glycol and dialkylene glycol alkyl ethers, such as more particularly ethylene glycol monoethyl ether, monomethyl ether propylene glycol 35 and diethylene glycol monoethyl ether.

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The solvents are preferably present in proportions of between 1 and 80% by weight relative to the total weight of the composition.

Physiologically acceptable media 5 can be thickened using thickening agents usually used in cosmetics or pharmacy, and heterobiopolysaccharides such as xanthan gum, scleroglucans, cellulose derivatives, polymers can be used. crosslinked acrylics or not.

The thickeners are preferably present in proportions of between 0.1 to 5% by weight, and in particular between 0.4 and 3% by weight relative to the total weight of each of the components when they are used separately , or relative to the total weight of the composition containing the components (A) and (B).

The compositions constituted, either by components (A) and (B) or by the composition containing the two components simultaneously, can also 2o contain any other adjuvants usually used in compositions intended for topical application for cosmetic or pharmaceutical use, and more particularly preservatives, complexing agents, colorants, basifying or acidifying agents, surfactants, anionic, cationic, nonionic, amphoteric, or mixtures thereof, anionic, cationic, nonionic or amphoteric polymers as well as their mixtures.

The pH of these compositions can vary between 4 30 and 9.

The antibacterial agents used in accordance with the invention may be present in component (A) in proportions of between 0.01 and 10% by weight relative to the total weight of component 35 (A) and in particular between 0.1 and 5% by weight and more ♦ 11 particularly still between 0.3 and 5% by weight.

The pyrimidine derivatives of formula (I) are used in component (B), preferably in proportions of between 0.05 and 10% by weight, and preferably between 0.1 and 5% by weight, and in particularly between 0.5 and 3% by weight relative to the total weight of the component (B).

In component (B), the pyrimidine derivatives of formula (I) may be present, either in dissolved form in physiologically acceptable media, or else in whole or in part in suspension in these media, in particular in the form of particles having a particle size less than 80 microns and preferably less than 20 microns, and in particular less than 5 microns.

One embodiment of the invention consists in using the combination as defined above in the form of a single composition containing the components (A) and (B). In this case, the concentration of antibacterial agents is preferably between 0.1 and 3% by weight relative to the total weight of the composition and that of the pyrimidine derivative of formula (I) is preferably between 0.5 and 3% by weight relative to the total weight of the composition.

A particularly preferred form of the invention consists in simultaneously applying the components (A) and (B) stored in separate devices and preferably containing the active substances, namely the antibacterial agent and the 3Q pyrimidine derivative in a mixture organic solvents comprising for example ethyl alcohol and propylene glycol or a mixture of solvent and water such as a mixture of water and ethyl alcohol and propylene glycol.

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Another embodiment consists in first applying the component (A) containing the antibiotic as defined above, then in applying the component (B) containing the pyrimidine derivative of formula (X) or vice versa, the applications being able to be carried out in immediate succession or shifted in time.

The combination according to the invention can be conditioned in these cases, in particular in a device with several compartments also called a "kit" or necessary, the first compartment containing the component (A) with the antibacterial agent, and the second compartment containing component (B) based on the pyrimidine derivative of formula (I). This device can be equipped with a means for mixing the components (A) and (B) just at the time of application.

The treatment for inducing and stimulating hair growth and reducing hair loss mainly consists in applying to the alopecic areas of the scalp of an individual, the combination as defined above, either by means of a single composition, either by applying components (A) and (B) or (B) and (A) successively and shifted in time.

The preferred mode of application consists in applying 1 to 2 g of the composition or of each of the components (A) and (B) to the alopecic zone at a frequency of one to two applications per day for 1 to 7 days per week. and this for a period of 1 to 30 6 months.

One of the objects of the invention, the treatment method for inducing and stimulating the growth of the hair or reducing hair loss, has the characteristics of a therapeutic treatment insofar as the combination in accordance with

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13 the invention has a therapeutic activity at the level of the biological mechanisms of the hair cycle and restores the dysfunction thereof.

A subject of the invention is therefore also a combination as defined above for its application as a medicament in the treatment of hair loss.

Another object of the invention is constituted by the use of the combination defined above 10 for the preparation of a medicament having the effect of inducing or stimulating the growth of the hair and of curbing its fall.

The process according to the invention finally has the characteristics of a cosmetic process insofar as it makes it possible to improve the aesthetics of the hair or of the scalp.

The following examples are intended to illustrate the invention without, however, being limiting in nature.

20 4 EXAMPLE 1 14

Two compositions (A) and (B) are respectively packaged containing: COMPOSITION (A): 5 - Erythromycin 0.5 g - Ethyl alcohol 95.0 g - Propylene glycol qs 100.0 g COMPOSITION (B): 10 - Minoxidil 2.0 g - Propylene glycol 20.0 g - Ethyl alcohol 50.0 g - Water qs 100.0 g 15

The compositions (A) and then (B) are successively applied one after the other to the alopecic parts of the scalp, at a rate of approximately 5 mg per cm 2. The daily treatment is continued over 2 2Q months. On examination of the trichogram, there is a significant increase in hair in the anagen phase.

EXAMPLE 2 * 15

Two compositions (A) and (B) are respectively packaged containing: COMPOSITION (A): 5 - Erythromycin estolate (or erythromycin 2 'propionate dodecylsulfate) 4.0 g - Propylene glycol 20.0 g - Ethyl alcohol 50, 0 g - Water qs 100.0 g 10 COMPOSITION (B): - Minoxidil 2.0 g - Ethyl alcohol 95.0 g 15 - Propylene glycol qs 100.0 g

The extemporaneous mixture of the two compositions (A) and (B) is applied.

We note results similar to those of 20 1 ’example 1.

P

16 EXAMPLE 3

Two compositions (A) and (B) are respectively packaged containing: COMPOSITION (A): 5 - Erythromycin ethylsuccinate (or erythromycin 2 'ethyl-butanedioate) 1/0 g - Ethyl alcohol 95.0 g - Propylene glycol qsp 100.0 g 10 COMPOSITION (B): - Minoxidil 2.0 g - Ethyl alcohol 95.0 g - Propylene glycol qs 100.0 g 15

The compositions (B) then (A) are applied successively a few hours apart.

Results similar to those of Example 1 are noted.

EXAMPLE 4 * 17

The following composition is prepared: - Erythromycin 0.5 g - Minoxidil 1.0 g 5 - Ethyl alcohol 95.0 g - Propylene glycol qs 100.0 g

Applied to the hair at a rate of 7 mg per minute, once a day for 2 months, 10 results are noted similar to those of Example 1.

EXAMPLE 5

The following composition is prepared: 15 - Erythromycin 1.0 g - Minoxidil 2.0 g - Ethyl alcohol 50.0 g - Propylene glycol 20.0 g 20 - Water qs 100.0 g

Applied to the hair at a rate of 4 mg per cm 3, 1 time per day for 2 months, results similar to those of Example 1 are noted.

25 18 EXAMPLE 6 *

A lotion with the following composition is prepared: - Spiramycin 1.0 g 5 - Minoxidil 1.0 g - Propylene glycol 20.0 g - Ethyl alcohol 50.0 g - Water qs 100.0 g 10 Applied to the hair at a rate of 7 mg per cm2, once a day for 2 months, results similar to those of Example 1 are noted.

EXAMPLE 7 15

A lotion of the following composition is prepared: - Tetracycline base 0.5 g 2o - Minoxidil 1.5 g - Ethyl alcohol 50.0 g - Propylene glycol 20.0 g - Water qs 100.0 g 25 Applied to the hair at the rate of 6 mg per cm2, once a day for 2 months, results similar to those of Example 1 are noted.

* 19 EXAMPLE 8

Two compositions (A) and (B) containing respectively:

Composition (A): 5 - Oleandomycin 0.5 g - Propylene glycol 20.0 g - Ethyl alcohol 50.0 g - Water qs 100.0 g 10

Composition (B): - Minoxidil 2.0 g - Propylene glycol 20.0 g 15 - Ethyl alcohol 50.0 g - Water qs 100.0 g

The compositions are applied in succession staggered in time, (A) in the morning, (B) in the evening.

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Results similar to those of Example 1 are noted.

EXAMPLE 9 20

Two compositions (A) and (B) containing respectively:

Composition (A): 5 - Tetracycline hydrochloride 1.0 g - Propylene glycol 20.0 g - Ethyl alcohol 50.0 g - Water qs 100.0 g 10 Composition (B): - Minoxidil with average particle diameter less than 2 microns 1 , 25 g - Crosslinked polyacrylic acid 15 PM: 3 million, sold under the name "CARBOPOL 934" by the

GOODRICH 1.0 g - Propylene glycol 4.5 g - 2-Amino-2-methyl-propanol-1 qs pH = 7 20 “Preservative qs - Water qs 100.0 g

The compositions are applied in succession staggered in time, in daily alternation: first day, the composition (A); second day, composition (B).

Results similar to those of Example 1 are noted.

* 21 EXAMPLE 10

The following composition is prepared: - Lincomycin 0.6 g - Minoxidil 0.5 g 5 - Ethyl alcohol 95.0 g - Propylene glycol qs 100.0 g

Applied to the hair at a rate of 8 mg per cm ^, 1 time per day for 2 months, there are 10 results similar to those of Example 1.

EXAMPLE 11

Two compositions (A) and 15 (B) containing in kit form respectively:

Composition (A): - Clindamycin 0.3 g 2o - Ethyl alcohol 50.0 g - Water qs 100.0 g

Composition (B): 25 - Minoxidil 1.0 g - Ethyl alcohol 95.0 g - Propylene glycol qs 100.0 g

The two compositions (A) then (B) 30 are applied in immediate succession.

Results similar to those of Example 1 are noted.

Claims (16)

22 " 1. Association intended to induce and stimulate hair growth and reduce hair loss, characterized in that it comprises: 5 a / a component (A) containing in a physiologically acceptable medium, at least one antibacterial agent chosen from antibiotics from the macrolide family, pyranosides and tetracyclines; and 10 b / a component (B) containing, in a physiologically acceptable medium, at least one pyrimidine derivative corresponding to the formula: H2Îjl ™ 2. Association according to claim 1, characterized in that the antibacterial agents of the macrolide family are chosen from erythromycin, Spiramycin, Oleandomycin, Roxytromycin, Josamycin and their derivatives and that the pyranosides are chosen among lincomycin, clindamycin and their derivatives. 3. Association according to claim 2, characterized in that the erythromycin derivatives are chosen from estolate, ethylcarbonate, ethylsuccinate, glucoheptonate, lactobionate, propionyl laurylsulfate, propionate, stearate, linoleate, mono-enic, bi- or tri-enic esters of erythromycin, all-trans and 13-cis retinoic acid esters of erythromycin A, as well as O-linoleoyl-2 erythromycin A, 10-linoleoyl-4 "erythromycin A and 1'0- -linoleoyl-4" erythromycin A, that the spiramycin derivatives are chosen from spiramycin di- or triacetate, that the clindamycin derivative is the hydrochloride. 4. Association according to any one of claims 1 to 3, characterized in that the lincomycin derivatives are chosen from lincomycin and lincomycin hydrochloride; that the clindamycin derivatives are chosen from clindamycin, and the hydrochloride, palmitate and phosphate of clindamycin, as well as the retinoic acid derivatives of lincomycin ♦ 24 and of clindaraycine. 5. Association according to any one of claims 1 to 4, characterized in that the tetracycline derivatives are chosen from 5 tetracycline, hydrochloride, N- (n-dodecyl) sulfamate, guaïcolglycolate, guaïcolsulfonate, laurylsulfate, metaphosphate, tetracyclinephosphate complex, tartrate complex, phenoxymethylpenicillinate, timolsulfonate, tetracycline trimethoxybenzoate trihydrate. 6. Association according to claim 5, characterized in that the pyrimidine derivative is araino-6 dihydro-1,2 hydroxy-1 iraino-2 piperidino-4 pyrimidine or Minoxidil. 7. Association according to any one of claims 1 to 6, characterized in that the antibacterial agent of the family of antibiotics is present in component (A) in proportions of between 0.01 and 10% by weight. relative to the total weight of the component (A) and in particular between 0.1 and 5% by weight, more particularly still between 0.3 and 5% and that the pyrimidine derivative of formula (I) is present in the component ( B) in proportions of between 0.05 and 10% by weight and preferably between 0.1 and 5% by weight, and in particular between 0.5 and 3% by weight. 8. Association according to any one of claims 1 to 7, characterized in that the association is present in a single composition, in which the antibacterial agent is present in proportions of between 0.1 and 3% by by weight and that the pyrimidine derivative of formula (I) is present in a proportion of between 0.5 and 3% by weight relative to the total weight of the composition. > ♦ 25 " 9. Association according to any one of claims 1 to 8, characterized in that the medium physiologically acceptable for the components (A) and (B) is a medium consisting of water or a mixture of water and one or more organic solvents or a mixture of organic solvents acceptable in cosmetics or in pharmacy. 10. Association according to any one of claims 1 to 9, characterized in that at least one of the components (A) or (B) contains a solvent chosen from lower C1-C4 alcohols, alkylene glycols, alkyl ethers of mono- and dialkylene glycol. 11. Association according to any one of claims 1 to 10, characterized in that at least one of the components (A) or (B) is thickened by means of thickening or gelling agents. 12. Association according to any one of claims 1 to 11, characterized in that at least one of the components (A) or (B) also contains a cosmetically or pharmaceutically acceptable adjuvant chosen from preserving agents, agents complexing agents, dyes, basifying or acidifying agents, surfactants, anionic, cationic, nonionic, amphoteric or mixtures thereof, anionic, cationic, nonionic or amphoteric polymers and mixtures thereof. 13. A method of cosmetic treatment of the hair or scalp, characterized in that the components (A) and (B) of the combination are applied as defined in any one of claims 1 to 12, either by means of a single composition, either separately or simultaneously, or successively or staggered in time. 26 t 14. Device with several compartments or "kit", characterized in that it comprises in a first compartment the component (A) as defined in any one of claims 1 to 13, and in a second compartment the component (B) as defined in any one of claims 1 to 13. 15. Association according to any one of claims 1 to 14, for its application as a medicament in the therapeutic treatment of hair loss. 15. T (DR? Ij ^^ N / 113 20 in which R- | denotes a group -N in which R3 and R4 can be chosen from hydrogen, an alkyl, alkenyl, alkylaryl or cycloalkyl group, R3 and R4 can also form a heterocycle with the nitrogen atom to which they are linked, chosen from the aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, hexahydroazepinyl, heptamethyleneimine, octamethyleneimine, morpholine and 4-alkyl piperazidinyl groups, the heterocyclic groups being able to be substituted carbon atoms with one to three lower alkyl, hydroxy or alkoxy groups; the group R2 is chosen from a hydrogen atom, an alkyl, alkenyl, alkylalkoxy, cycloalkyl, aryl, alkylaryl, arylalkyl, alkylaryl-alkyl, alkoxyarylalkyl group or haloarylalkyl, as well as the physiologically acceptable acid addition salts, the components (A) and (B) being part of the same composition and being intended to be used separately arement, either simultaneously, or successively or staggered in time, on the scalp or hair. 16. Use of the combination according to any one of claims 1 to 12, for the preparation of a medicament intended for the therapeutic treatment of hair loss. Drawings; ......... boards ........ cone ......... yd .... cover page ........ description psçjss. ...... 3 of claim,, ..... A ·· · "· '·· descriptive Lursn-ii.r .: · qq rf £ The mandr: Me Alain K'uksvins