LU87067A1 - COMPOSITION FOR INDUCING AND STIMULATING HAIR GROWTH AND / OR BRAKING HAIR LOSS, BASED ON A NON-IONIC SURFACTANT AND A PYRIMIDINE DERIVATIVE - Google Patents

Abstract

Composition for inducing and stimulating hair growth and/or reducing hair loss, which contains, in a cosmetically or pharmaceutically acceptable medium, at least one non-ionic surfactant chosen from polyhydroxypropyl ethers and oxyethylenated alkylphenols and at least one compound 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, this heterocycle being chosen from aziridinyl, azetidinyl, pyrrolidinyl, piperidyl, hexahydroazepinyl, heptamethylenimine, octamethylenimine, morpholine and 4-(lower alkyl)piperazinyl groups, it being possible for the heterocyclic groups to be substituted on the carbon atoms with one to three alkyl, hydroxyl or alkoxy groups; the group R2 is chosen from hydrogen and an alkyl, alkenyl, alkyloxy, cycloalkyl, aryl, alkylaryl, arylalkyl, alkylarylalkyl, alkoxyarylalkyl and/or haloarylalkyl group; as well as the addition salts with cosmetically or pharmaceutically acceptable acids.

Description

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Composition for inducing and stimulating hair growth and / or slowing hair loss, based on a nonionic surfactant and a pyrimidine derivative.

5 The present invention relates to a composition for inducing and stimulating hair growth and / or slowing hair loss, containing, in combination, at least one pyrimidine derivative and at least one nonionic surfactant.

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. .

Three phases are observed successively during a hair cycle, 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 a hair emerging in the anagen phase.

15 This permanent physical renewal process undergoes a natural evolution during aging, the hair becomes thinner, their 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 which can lead to more or less pronounced alopecia. Among these factors, we can cite food, endocrine, nervous factors, etc.

The variation of these different hair categories is determined using the trichogram or phot ot r i chog ramme.

35 We have been researching for many years in

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3 the cosmetic or pharmaceutical industry of compositions making it possible to suppress or reduce alopecia and in particular to induce or stimulate hair growth or to reduce their fall.

With this in mind, compounds such as 6-amino-1,2-dihydro-1-hydroxy-2-imino-piperidino-4 pyrimidine and its derivatives have already been proposed. Such compounds are described in particular in US Pat. No. 4,139,619.

To increase the effectiveness of the compositions containing the pyrimidine derivatives, it has been found advantageous to seek a well tolerated composition containing the pyrimidine derivative (s) which is capable of remaining in contact with the scalp without being rinsed. for a prolonged period in order to promote the penetration of the active substance into the stratum corneum.

With this in mind, the Applicant has discovered that compositions containing certain particular surfactants make it possible to improve the effectiveness of the compositions based on pyrimidine derivative (s).

The combination of these two compounds makes it possible in particular to obtain, compared with those previously known, more effective compositions, requiring no rinsing for an extended period of time, and very well tolerated. It also makes it possible to produce new dosage forms which are particularly well suited to the application of the active principle and to the possibility of carrying out a remarkably easy elimination by simple rinsing with water on the hair and the scalp.

Thanks to the greater effectiveness of the compositions containing the combination according to the invention, it is possible to obtain, compared to the compositions of the prior art, for the same concentration of active substance, a greater activity and for a concentration of weaker active substance, faster activity.

The Applicant has further discovered that, unlike other compositions associating the pyrimidine derivative (s) with surfactants conventionally used in the field of cosmetics, the compositions proposed according to the present invention exhibited excellent stability over time without decrease in concentration of active substance and that they showed no irritation of the scalp after prolonged contact for several hours without being rinsed.

The subject of the present invention is therefore a new composition for inducing and stimulating hair growth and / or slowing hair loss, containing, in a physiologically acceptable medium, at least one nonionic surfactant chosen from polyhydroxypropyl ethers, ethers polyoxyethylenated fatty alcohols, oxyethylenated alkylphenols, mixtures of fatty alcohols and polyoxyethylenated fatty alcohols and at least one compound corresponding to the formula; 25

H2N N HH

(I)

Ro. .NOT

X

/ R3

in which R- | denotes a group -N

^ * 4

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5 in which: R3 and R4 can be chosen from: hydrogen, an alkyl group, preferably having 1 to 4 carbon atoms, alkenyl, alkylaryl or lower cycloalkyl, R3 and R4 can also form a heterocycle with the atom of nitrogen to which they are linked, this heterocycle being chosen from aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, hexahydroazepinyl, heptamethyleneimine, octamethyleneimine, morpholine and lower alkyl-4-piperazidinyl groups, heterocyclic groups which may be substituted on the atoms carbon by one to three lower alkyl, hydroxy or alkoxy · groups; The group R2 is chosen from hydrogen, an alkyl, alkenyl, alkylalkoxy, cycloalkyl, aryl, alkylaryl, arylalkyl, alkylarylalkyl, alkoxyarylalkyl and lower haloarylalkyl group, as well as cosmetically or pharmaceutically acceptable acid addition salts.

In formula (I), alkyl or alkoxy preferably denotes a group having 1 to 4 carbon atoms, alkenyl preferably denotes a group having 2 to 5 carbon atoms and aryl preferably denotes phenyl.

The compounds of formula (I) which are more particularly preferred are chosen from the compounds in which R2 denotes hydrogen, and R1 represents a group -N, in which R3 and R4 form a piperidinyl ring as well as their salts such as for example sulfate.

The more particularly preferred compound is amino-6 dihydro-1,2 hydroxy-1 imino-2 piperidino-4

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6 pyrimidine or "Minoxidil".

The nonionic poly (hydroxypropyl ether) surfactants used more particularly according to the invention are chosen from the compounds of formulas 5 (II) to (IV) below and / or from the compounds prepared according to the methods described in paragraphs (3) and (4) below: (1) R5O - (CH2 - ÇHO-hn-H (II)

CH2OH

10 where R5 denotes a radical or a mixture of alkyl radicals containing 10 to 14 carbon atoms and m is an integer or decimal number from 2 to 10 and preferably from 3 to 6. These compounds of formula (II) can be prepared according to the method described in patent FR-1,477,048; (2) R6-C0NH-CH2-CH2-0-CH2-CH2-0 (CH2-CH0H-CH2 "0-hrH (III) where Rg denotes a radical or a mixture of alkyl and / or alkenyl radicals having from 11 to 17 carbon atoms, and n denotes an integer or decimal number from 1 to 5 and preferably 1.5 to 4.

These compounds of formula (III) can be prepared according to the process described in patent FR-2,328,763; (3) compounds of formula R7CH0H-CH2-O (CH2_CH0H-CH2-0> p-fl (IV) in which R7 denotes an aliphatic, cycloaliphatic, arylaliphatic radical, preferably having 7 3q with 21 carbon atoms, and their mixtures, the aliphatic chains denoting in particular alkyl chains which may contain 1 to 6 ether, thioether and / or hydroxymethylene groups and p is a number between 1 and 10 inclusive.

These compounds are prepared by condensation in alkaline catalysis of 2 to 10 and preferably 2.5 to 6 moles of glycidol on an alpha-diol or a mixture of C- | qC- | 4 alpha-diols to the temperature of 120-180 ° C and preferably 140-160 ° C, the glycidol being added slowly according to the preparation process described in patent FR-2,091,516; (4) compounds prepared by condensation, in acid catalysis, from 2 to 10 and preferably from 2.5 to 6 moles of glycidol per mole of alcohol or of alpha-diol containing 10 10 to 14 carbon atoms at a temperature from 50 to 120 ° C, the glycidol being added slowly to the alcohol or to the alpha-diol, the process for the preparation of these compounds being described in patent FR-2,169,787; (5) poly (hydroxypropyl ether) compounds prepared by (poly) addition of glycerol monochlorohydrin on an organic (poly) hydroxylated compound in the presence of a strong base, by elimination as water is obtained by distillation, described in particular in French patent FR-2,574,786.

Among the nonionic poly (hydroxypropylether) surfactants described under paragraphs (1), (2), (3), (4) and (5) above, the following compounds are preferred: -C12H25O - (CH2 - CH - 0 -) - H (V) 25 4.2

CH2OH

-R5O - (CH2 - ÇH - 0 -) - H (VI) 3.75

30 CH20H

where R5 denotes a mixture of C1oH21 and C12H25 alkyl radicals; the compounds prepared by condensation in alkaline catalysis of 3.5 moles of glycidol on a mixture of alpha-diols having from 11 to 14 carbon atoms, according to the process described in patent FR-2,091,516; - and the compounds of formula: R6-C0NH-CH2-CH2-0-CH2-CH2-0- (CH2-CH0H-CH2-0 ') - H (VII).

3.5 where Rβ denotes a mixture of radicals comprising the following alkyl and alkenyl radicals: C11H23, Ci3H27f radicals derived from coconut fatty acids, radical derived from oleic acid.

10 “Iss compounds prepared by condensation of 3.5 moles of glycidol on a mixture of alpha-diols in Cll ~ Ci4, according to patent FR-2,091,516, the nonionic surfactant poly (hydroxypropylether) obtained by condensation of monochlorhydrihe (2.5 moles) in the presence of sodium hydroxide on 1,2-dodecanediol are particularly preferred.

The polyoxyethylenated fatty alcohol ethers are preferably polyethylene glycol ethers of a mixture of synthetic fatty alcohols having 10 to 22 20 carbon atoms and preferably 11 to 15 carbon atoms, with approximately 1 to 12 moles of oxide of ethylene and preferably 7 moles of ethylene oxide, such as for example the product sold under the name TERGITOL 15-S7 by the company UNION CARBIDE.

The mixture of fatty alcohols and polyoxyethylenated fatty alcohols is preferably a mixture of C 10 -C 22 alcohols and C 10-2 22 oxyethylenated alcohols with 2 to 50 moles of ethylene oxide, in relative proportions from 10:90 to 90:10, such as in particular a mixture of cetylstearyl alcohol (80%) and cetylstearyl alcohol oxyethylenated to 33 moles of ethylene oxide (20%) such as for example product sold under the name SINNOWAX AO by the company HENKEL.

9

The oxyethylenated alkylphenols contain 5 to 35 moles of ethylene oxide and the alkyl radical preferably contains 8 or 9 carbon atoms in the chain, such as for example the products sold under the name Antarox by the company GAF Corp.

A more particularly preferred composition, in accordance with the invention, consists of a composition containing, in a cosmetically or pharmaceutically acceptable medium, at least 6-amino-1,2-dihydro-1,2-hydroxy-1 imino-2 piperidino-4 pyrimidine and a poly (hydroxypropyl ether) nonionic surfactant defined above.

The pyrimidine derivative of formula I is used in the compositions according to the invention in a proportion of 0.05 to 6% by weight relative to the total weight of the composition, and preferably from 0.1 to 3% and more particularly from 0.5 to 2%.

The nonionic surfactant is used in proportions of between 1 and 30% by weight relative to the total weight of the composition and preferably from 5 to 15%.

The cosmetically or pharmaceutically acceptable medium can be an aqueous medium or a mixture of water and a cosmetically or pharmaceutically acceptable solvent thickened or not.

As solvent there may be used in particular lower C1-4 alcohols such as ethyl alcohol, isopropyl alcohol and tert-butyl alcohol, alkylene glycols such as propylene glycol and alkyl ethers of mono- and dialkylene glycols such as ethylene glycol monoethyl ether, propylene glycol monomethyl ether and diethylene glycol monoethyl ether.

As thickeners, thickeners may be used which are well known in the state of the art, of which there may be mentioned more particularly, by way of nonlimiting example, heterobiopoly-saccharides such as xanthan gum or scleroglucans, cellulose derivatives, acrylic polymers crosslinked or not.

These thickeners are preferably used in proportions of between 0.1 and 5% by weight relative to the total weight of the composition.

These compositions may optionally contain the ingredients conventionally used in cosmetic or pharmaceutical compositions such as preserving agents, complexing agents, dyes, basifying or acidifying agents, perfumes, polymers.

The pH of these compositions is between 4 and 9 and preferably between 7 and 8.5.

They can be in the form of thickened or non-thickened lotions, gels, creams, emulsions and can be pressurized in aerosol devices.

The treatment method for combating hair loss and / or stimulating their growth consists mainly in applying to the alopecic areas of the scalp and the hair of an individual a composition as defined above, to be left in contact several hours and possibly rinse.

It is possible, for example, to apply the composition to the hair and the scalp in the evening, to keep the composition overnight and optionally to carry out a shampoo in the morning or to wash the hair with the aid of said composition and leave it in contact again for a few minutes. before rinsing.

The process according to the invention has the characteristics of a therapeutic treatment of alopecia insofar as the composition acts on the biological mechanisms and in particular on the hair cycle.

It also has the characteristics of a cosmetic treatment insofar as it makes it possible to beautify the hair and the scalp.

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

EXAMPLE 1 10

The following composition is prepared: - Amino-6 dihydro-1,2 hydroxy-1 imino-2 pipinoidino-4 pyrimidine · 0.50 g 15 - Xanthan gum sold under the name "KELZAN K9 C57" by the

Company KELCO 1.00 g - Nonionic surfactant poly (hydroxypropyl ether) prepared by condensation in alkaline catalysis of 3.5 moles of glycidol on a mixture of alpha-diols having 11 to 14 carbon atoms, according to the process described in · patent FR-2,091,516 10.00 g - Water qs 100.00 g 25 EXAMPLE 2

The lotion with the following composition is prepared: 30. - Amino-6 dihydro-1,2 hydroxy-1 imino-2 piperidino-4 pyrimidine 0.25 g - Nonionic surfactant poly (hydroxy-propylether) of formula: 12

Cl2H250- (CH2-CH-O) -H 5.00 g 4.2 ch2oh - Water qs 100.00 g 5 EXAMPLE 3

The lotion with the following composition is prepared: - Amino-6 dihydro-1,2 hydroxy-1 imino-2 piperidino-4 pyrimidine 0.55 g - Nonionic surfactant poly (hydroxy-propylether) of formula:

R-C0NH- (CH2) 2-0- (CH2) 2 “0- (CH2-CH0H-CH2-0 -} - H

3.5 15 where R denotes the following mixture of alkyl and alkenyl radicals: 35% C12H25 “15% C14H29 - 15% oleyl radicals - 35% radicals derived from coconut fatty acids 12.00 g 20 - Water qs 100.00 g % 13 EXAMPLE 4

The lotion of the following composition is prepared: - Amino-6 dihydro-1,2 hydroxy-1 imino-2 5 piperidino-4 pyrimidine 2.00 g - Non-ionic surfactant poly (hydroxy-propylether) obtained by condensation of monochlorohydrin glycerol (2.5 moles) in the presence of sodium hydroxide on dodecanediol-1,2 according to French patent FR-25.74.786 10.00 g - Propylene glycol 20.00 g - Ethyl alcohol · 50.00 g - Water qs 100.00 g 15

This composition is applied to the scalp and hair in the evening and the ori rinses with water the next morning.

20 EXAMPLE 5

The lotion of the following composition is prepared: - Amino-6 dihydro-1,2 hydroxy-1 imino-2 25 piperidino-4 pyrimidine 0.45 g

- Mixture of cetylstearyl alcohol (80%) and oxyethylenated cetylstearyl alcohol containing 33 moles of ethylene oxide (20%) sold under the name SINNOWAX AO

30 by the company HENKEL 8.00 g - Water qs 100.00 g '------ * 14 EXAMPLE 6

The lotion of the following composition is prepared: - Amino-6 dihydro-1,2 hydroxy-1 imino-2 piperidino-4 pyrimidine 0.60 g 5 - Polyethylene glycol ether of a mixture of synthetic fatty alcohol C11-15 oxyethylenated to around 7 moles of ethylene oxide, sold under the name TERGITOL 15 S-7 by the company UNION 10 CARBIDE '15.00 g - Water qs 100.00 g

The compositions of Examples 1 to 6 were applied to the scalp at the rate of ... g on a surface of ............ It is found that the composition does not run and is eliminated easily rinsed leaving hair shiny and light.

Applied for 2 months at the rate of an application in the evening and a rinse in the morning, it can be seen that the ratio:

Anagen Telogen increases significantly.

Claims (19)

15 1. Composition for inducing and stimulating hair growth and / or slowing hair loss, characterized in that it contains, in a cosmetically or pharmaceutically acceptable medium, at least one nonionic surfactant chosen from poly (hydroxypropyl ethers) , polyoxyethylenated fatty alcohol ethers, oxyethylenated alkylphenols, mixtures of fatty alcohols and polyoxyethylenated fatty alcohols, and at least one compound corresponding to the formula: νΛ / 15 Ro -N “V r3 20 in which Ri denotes a group Tl4 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, this heterocycle being chosen from aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, hexahydroazepinyl, heptamethyleneimine, octamethylene-imine, morpholine and lower alkyl-4-piperazidinyl groups, groupings heterocyclic ts which can be substituted on the carbon atoms by one to three alkyl, hydroxy or alkoxy groups; * 16 the group R2 is chosen from hydrogen, an alkyl, alkenyl, alkylalkoxy, cycloalkyl, aryl, alkylaryl, arylalkyl, alkylarylalkyl, alkoxyarylalkyl and / or haloarylalkyl group, as well as the addition salts of acids cosmetically or pharmaceutically acceptable. 2. Composition according to Claim 1, characterized in that the compound (I) is a compound in which R2 denotes hydrogen and Ri 10 represents the group -N, in which R3 and R4 form a \ r4 piperidinyl ring or l 'one of its salts. 3. Composition according to Claim 1, characterized in that the compound of formula (I) is 6-amino-1,2-dihydro-1,2-hydroxy-2-imino-4 piperidino-pyrimidine or "minoxidil". 4. Composition according to any one of claims 1 to 3, characterized in that the nonionic surfactant is a poly (hydroxypropyl ether) chosen from the group formed by: (1) the compounds of formula (II): R5O - (CH2 - CHOim-H (II) CH20H where R5 denotes a radical or a mixture of alkyl radicals containing 10 to 14 carbon atoms and m is an integer or decimal number from 2 to 10 and preferably from 3 to 6; (2) the compounds of formula (III): R6-C0NH-CH2 “CH2“ 0-CH2 "CH2“ 0 (CH2_CH0H-CH2 ~ 0 ') - rj — H (III) where Rg denotes a radical or a mixture alkyl and / or alkenyl radicals having from 11 to 17 carbon atoms and n denotes an integer or decimal number from 1 to 17 5 and preferably from 1.5 to 4; (3) the compounds of formula: R7CHOH-CH2 -O (CH2-CH0a-CH2-O) p — H (IV) in which R7 denotes an aliphatic, cycloaliphatic, arylaliphatic radical, preferably having 7 to 21 carbon atoms, and their mixtures, the aliphatic chains denoting in particular alkyl chains which may contain 1 to 6 ether, thioether and / or hydroxymethylene groups and p is a number between 10 1 and 10 inclusive; (4) the compounds prepared by condensation in acid catalysis, from 2 to 10 and preferably from 2 , 5 to 6 moles of glycidol per mole of alcohol or alpha-diol containing 10 to 14 carbon atoms; 15 (5) poly (hydroxypropyl ether) compounds prepared by (poly) addition of monochlorohydrin of glycerol on a poly (hydroxylated) organic compound in the presence of a strong base and elimination of water. 5. Composition according to Claim 4, characterized in that the nonionic surfactant poly (hydroxypropylether) is chosen from the compounds of formulas: c12H25 ° “(CH2 - ch - O) -H (IV) 4.2 25 CH2OH R5O - (CH2 - CH - O ·) -H (V) 3.75 CH2OH 30 where R5 denotes a mixture of alkyl radicals C10H21 and C12H25 · 6. Composition according to claim 4, characterized in that the nonionic surfactant of poly (hydroxypropylether) is the compound: * 18 R6-C0NH-CH2-CH2-0-CH2-CH2-0- (CH2-CH0H -CH2-0 -) - H (VI) 3.5 where Rg denotes a mixture of radicals comprising the following alkyl and alkenyl radicals: 5 ^ 11 ^ 23 'C13H27, radicals derived from coconut fatty acids, radical derived from oleic acid. „7. Composition according to claim 4, characterized in that the nonionic surfactant poly (hydroxypropylether) is prepared by condensation in alkaline catalysis of 3.5 moles of glycidol on a mixture of alpha-diols having 11 has 14 carbon atoms. 8. Composition according to claim 4, characterized in that the poly (hydroxypropyl ether) compound (5) is obtained by condensation of monochlorohydrin (2.5 moles) in the presence of sodium hydroxide on 1,2-dodecanediol . 9. Composition according to any one of claims 1 to 3, characterized in that the nonionic surfactant is a polyethylene glycol ether of a mixture of fatty alcohols having 10 to 22 carbon atoms with about 1 to 12 moles ethylene oxide. 10. · Composition according to any one of claims 1 to 3, characterized in that the nonionic surfactant is a mixture of fatty alcohols Ci0 “c22 and alcohols C- | o-C22 oxyethylenated 2 to 50 moles of ethylene oxide. 11. Composition according to any one of claims 1 to 3, characterized in that the nonionic surfactant is a C8 ”C9 alkyl pheny oxyethylenated. 12. Composition according to claim 1, characterized in that it contains the amino-6-dihydro-1,2-hydroxy-1 imino-2 piperidino-4 pyrimidine and a nonionic surfactant of poly (hydroxypropylether). Wwin · 7'1 "- · ......> t 19 13. Composition according to any one of claims 1 to 12, characterized in that the compound of formula (I) is present in proportions of between 0.05 and 6% by weight relative to the total weight of the composition and preferably between 0.1 and 3% by weight. 14. Composition according to any one of claims 1 to 13, characterized in that the nonionic surfactant is present in proportions of between 1 and 30% by weight relative to the total weight of the composition and preferably between 5 and 15% by weight. 15. Composition according to any one of claims 1 to 14, characterized in that the cosmetically or pharmaceutically acceptable medium consists of water or a mixture of water and a cosmetically or pharmaceutically acceptable solvent, thickened or not. 16. Composition according to Claim 15, 20 characterized in that it contains thickening agents in proportions of between 0.1 and 5% by weight relative to the total weight of the composition. · 17. A method of cosmetic treatment of the hair, characterized in that at least one composition as defined in any one of claims 1 to 16 is applied to the hair or the scalp which is left in contact and eventually rinse. 18. Composition according to any one of claims 1 to 16 for its application in the therapeutic treatment of alopecia. 19. Use of the composition according to any one of claims 1 to 16 for the preparation of a medicament intended for the treatment of alopecia.