(en)A composition for inducing and stimulating hair growth and/or reducing hair loss comprises at least one alkylpolyglycoside and at least one compound having formula (I) in a physiologically acceptable medium. ##STR1## In compound (I) , R 1 represents the group ##STR2## where in R 3 and R 4 may be selected from hydrogen, alkyl, alkenyl or cycloalkyl. R 3 and R 4 may also form a heterocycle with the nitrogen atom to which they are bonded. The heterocycle may be an aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, hexahydroazepinyl, heptamethyleneimine, octamethyleneimine, morpholine or 4-low alkylpiperazidinyl group. These heterocycles may be substituted at the carbon atoms by one to three alkyl, hydroxy or alkoxy groups. R 2 is selected from hydrogen, alkyl, alkenyl, alkylalkoxy, cycloalkyl, aryl, alkylaryl, arylalkyl, alkylarylalkyl, alkoxyarylalkyl and/or haloarylalkyl. The physiologically acceptable acid addition salts of the compound may also be used.

1.ApplicationNumber: US-21466894-A
1.PublishNumber: US-5567701-A
2.Date Publish: 19961022
3.Inventor: GROLLIER; JEAN F.

4.Inventor Harmonized: GROLLIER JEAN F(FR)

5.Country: US
6.Claims:
(en)A composition for inducing and stimulating hair growth and/or reducing hair loss comprises at least one alkylpolyglycoside and at least one compound having formula (I) in a physiologically acceptable medium. ##STR1## In compound (I) , R 1 represents the group ##STR2## where in R 3 and R 4 may be selected from hydrogen, alkyl, alkenyl or cycloalkyl. R 3 and R 4 may also form a heterocycle with the nitrogen atom to which they are bonded. The heterocycle may be an aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, hexahydroazepinyl, heptamethyleneimine, octamethyleneimine, morpholine or 4-low alkylpiperazidinyl group. These heterocycles may be substituted at the carbon atoms by one to three alkyl, hydroxy or alkoxy groups. R 2 is selected from hydrogen, alkyl, alkenyl, alkylalkoxy, cycloalkyl, aryl, alkylaryl, arylalkyl, alkylarylalkyl, alkoxyarylalkyl and/or haloarylalkyl. The physiologically acceptable acid addition salts of the compound may also be used.

7.Description:
(en)This application is a continuation of application Ser. No. 07/815,872, filed Jan. 3, 1992, abandoned, which is a continuation of application Ser. No. 07/397,253, filed Aug. 23, 1989, abandoned.


BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention concerns a composition for inducing and stimulating hair growth and/or reducing its loss containing, in combination, at least one pyrimidine derivative and at least one alkylpolyglycoside surfactant.
Man has about 100 000 to 150 000 hairs on the head and a daily loss of 50 to 100 hairs is normal. Maintaining a head of hair is essentially dependent on a pilary cycle during which the hair is formed, grows and then falls out before being replaced by a new hair growing from the same follicle.
Three phases occur during the pilary cycle: the anagenous, catagenous and telogenous phases.
During the first or anagenous phase the hair undergoes a period of active growth associated with intense metabolic activity in the root.
The second or catagenous phase is transitory and characterised by a slowing down of metabolic activity. During this phase the hair undergoes involution, the follicle atrophies and its dermal implantation appears higher and higher.
The final or telogenous phase corresponds to a rest period for the follicle and the hair finally falls out, pushed out by a new hair in its anagenous phase.
This permanent renewal process undergoes a natural evolution during ageing whereby the hair becomes finer and the cycles shorter.
Alopecia occurs when this physical renewal process is accelerated or perturbed, ie growth phases are shortened, passage of hair into the telogenous phase speeds up and hair falls out more frequently. Successive growth cycles result in finer and finer, shorter and shorter hair, gradually resulting in unpigmented down. This phenomenon may result in baldness.
Several factors, eg alimentary, endocrinal or nervous factors, may affect the pilary cycle and result in more or less pronounced alopecia.
Variations in the different phases may be determined using a trichogram, in particular a phototrichogram.
For several years, the cosmetics and pharmaceuticals industries have sought compositions which will cure or reduce alopecia, particularly ones which will induce or stimulate hair growth or reduce hair loss.
2. Description of the Prior Art
In this respect compositions such as 6-amino -1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine and its derivatives have already been used. Such compositions are described in U.S. Pat. No. 4,139,619 in particular.
In order to improve the efficacy of compositions containing pyrimidic derivatives, a composition has been sought which is tolerated well and contains pyrimidine derivative(s) which can remain in contact with the scalp over a prolonged period without being rinsed away, to encourage penetration of the active substance into the horny layer.
In this regard the applicant has discovered that by using an alkylpolyglycoside in combination with the pyrimidine derivatives it is possible to improve the efficacy of the composition in inducing and stimulating hair growth and reducing hair loss.
Combinations of the two compounds can produce compositions which are more efficaceous than those previously known and which can be used in a manner which is particularly easy and appropriate for application of active ingredients.
Use of an alkylpolyglycoside in combination with the pyrimidine derivative also allows remarkably easy elimination of the composition simply by rinsing.
The applicant has also established that the composition has good storage properties.
A composition according to the invention is also cosmetically suitable and does not cause irritation of the scalp even after prolonged contact without rinsing.
An object of the invention, therefore, is to provide a novel alkylpolyglycoside and pyrimidine derivative based composition to induce and stimulate hair growth and/or reduce its loss.
Another object of the invention is to provide pharmaceutical compositions for topical application based on this composition.
A further object of the invention is to provide a cosmetic hair and scalp treatment method using this composition.
Further objects of the invention will become clear from the following description and examples.
SUMMARY OF THE INVENTION
A composition according to the invention for inducing and stimulating hair growth and/or reducing hair loss comprises, in a physiologically acceptable medium, at least one alkylpolyglycoside and at least one compound having formula: ##STR3## wherein R 1 represents the group ##STR4## and wherein: R 3 and R 4 may be selected from hydrogen, an alkyl group preferably containing one to four carbon atoms, an alkenyl, alkylaryl or cycloalkyl group in which the alkyl portion is a lower alkyl radical;
R 3 and R 4 may also form a heterocycle with the nitrogen atom to which they are bonded, said heterocycle being selected from the following groups: aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, hexahydroazepinyl, heptamethyleneimine, octamethyleneimine, morpholine and low 4-(lower alkyl)piperazidinyl, the heterocyclic groups also being substituted at the carbon atoms by one to three lower alkyl, hydroxy or alkoxy groups;
R 2 is selected from hydrogen or an alkyl, alkenyl, alkylalkoxy, cycloalkyl, aryl, alkylaryl, arylalkyl, alkylarylalkyl, alkoxyarylalkyl and haloarylalkyl group, the alkyl portion of which is a lower alkyl radical, and cosmetically or pharmaceutically acceptable addition salts of associated acids.
In formula (I), alkyl or alkoxy preferably designates a group having one to four carbon atoms; alkenyl preferably designates a group having two to five carbon atoms and aryl preferably designates phenyl.
Particularly preferred compounds having formula (I) are those wherein R 2 designates hydrogen and R 1 represents the group ##STR5## where R 3 and R 4 form a piperidinyl ring, as well as their salts, for example the sulfate.
A particularly preferred compound is 6-amino -1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine or "Minoxidil".
Alkylpolyglycosides used according to the invention have formula (II):

C.sub.n H.sub.2n+1 (C.sub.6 H.sub.10 O.sub.5).sub.x H (II)

or correspond to the diagrammatic structure (III): ##STR6## wherein: n is an integer between 8 and 15,
x is an integer from 1 to 10.
Such products are sold by HORIZON CHEMICAL under the trade name APG.
A particularly preferred product has formula (II) wherein:
n is between 8 and 11, and
x is between 1 and 10.
Such a product is marketed by HORIZON CHEMICAL under the name APG 300 or APG 500 as an aqueous solution containing 50% active material.
The pyrimidine derivative of formula (I) is used in compositions according to the invention in a proportion of 0.05 to 6% by weight with respect to total composition weight, preferably 0.1 to 3% and advantageously 0.5 to 2%.
The alkylpolyglycoside surfactant is used in a proportion of 1 to 30% by weight with respect to total composition weight, preferably 5 to 15%.
The physiologically acceptable medium is one which is appropriate for cosmetic or pharmaceutical use and may be an aqueous medium or a mixture of water and a cosmetically or pharmaceutically acceptable solvent. It may be thickened.
The following solvents may particularly be used: C 1 to C 4 low alcohols such as ethanol, isopropanol and tert-butanol; alkyleneglycols such as propyleneglycol and alkylethers of mono- and dialkyleneglycol eg ethyleneglycol monoethylether, propyleneglycol monomethylether and diethyleneglycol monoethylether.
When used the aqueous medium, solvents are present in a proportion of 0.5 to 80% by weight with respect to total composition weight.
Known thickening agents may be used, particularly (but not exclusively): the diethanolamide of copra acids, heteropolysaccharides such as xanthane gum or scleroglucanes, cellulose derivatives and reticulated or non-reticulated acrylic polymers and polyethyleneglycols and their derivatives.
These thickeners are preferably used in a proportion of 0.1 to 6% by weight with respect to total composition weight.
These compositions may also contain ingredients normally employed in cosmetic or pharmaceutical compositions, such as preservatives, complexing agents, dyes, acidifying or alkalizing agents, perfumes or polymers.
The pH-of the compositions lies between 4 and 9, preferably between 7 and 8.5.
These compositions may be packaged in aerosols. A method for the treatment of hair loss and/or stimulating hair growth principally consists in applying a composition as hereinbefore defined to alopecic areas of the scalp and hair, leaving it in contact therewith for several hours and, if necessary, rinsing it out.
The composition may, for example, be applied in the evening, left on overnight and shampooed out the following morning, or the hair could be washed again with more composition and left for a few minutes before rinsing out.
It has been observed that the inventive composition is particularly effective when applied as a capillary lotion, either as a rinse or as a shampoo.
The inventive method has the characteristics of a therapeutic treatment for alopecia in that the composition affects biological mechanisms, particularly the pilary cycle, to correct their dysfunction.
The method also has the characteristics of a cosmetic treatment in that it can improve the hair condition.
The following examples are intended to illustrate the invention without in any way limiting its scope.


EXAMPLES OF THE INVENTION
EXAMPLE 1
A shampoo using the following composition was prepared:

______________________________________Alkylpolyglycoside APG 300 sold by 12.0 g AMHORIZON CHEMICAL as an aqueoussolution containing 50% activematerial (AM)Minoxidil 0.5 gDisodium salt of ethylenediamino 0.2 gtetracetic acidPreservative(s) qsWater qsp 100.0 g______________________________________

The shampoo was applied to the hair, massaging the scalp.
It was left for several minutes and then rinsed out and the hair was then dried.
EXAMPLE 2
A lotion having the following composition was prepared:

______________________________________Alkylpolyglycoside APG 300 sold by 5.0 g AMHORIZON CHEMICAL as an aqueoussolution containing 50% activematerial (AM)Minoxidil 0.5 gEthanol 15.0 gWater qsp 100.0 g______________________________________

The lotion was applied to the scalp, left for 30 minutes and then rinsed out.
EXAMPLE 3
A capillary solution having the following composition was prepared:

______________________________________Alkylpolyglycoside APG 300 sold by 5.0 g AMHORIZON CHEMICAL as an aqueoussolution containing 50% activematerial (AM)Minoxidil 0.5 gPropyleneglycol monomethylether 20.0 gPreservative(s) qsWater qsp 100.0 g______________________________________

The lotion was applied to the scalp, left for 30 minutes and then rinsed out.
EXAMPLE 4
A shampoo having the following composition was prepared:

______________________________________Alkylpolyglycoside APG 300 sold by 15.0 g AMHORIZON CHEMICAL as an aqueoussolution containing 50% activematerial (AM)Minoxidil 0.5 gDiethanolamide of copra acids 5.0 gDisodium salt of ethylenediamino 0.2 gtetracetic acidWater qsp 100.0 g______________________________________

This composition was shampooed in and rinsed out and the hair was then dried.
EXAMPLE 5
A capillary lotion having the following composition was prepared:

______________________________________Alkylpolyglycoside APG 350 sold by 6.0 g AMHORIZON CHEMICAL as an aqueoussolution containing 50% activematerial (AM)Minoxidil 0.15 gEthanol 29.84 gComplexing agent qsWater qsp 100.0 g______________________________________

This lotion was applied to alopecic areas of the scalp but not rinsed out.
EXAMPLE 6
A GEL shampoo having the following composition was prepared:

______________________________________Alkylpolyglycoside (APG 500) sold 13.0 g AMby HENKEL under the trade nameMERGITAL CG 60 as an aqueous solutioncontaining 60% active material (AM)Minoxidil 0.5 gThickener: PEG derivative 0.75 gPreservatives, complexing agent qsWater qsp 100.0 g______________________________________

EXAMPLE 7
A MOUSSE shampoo having the following composition was prepared:

______________________________________Alkylpolyglycoside (APG 500) sold 13.0 g AMby HENKEL under the trade nameMERGITAL CG 60 as an aqueous solutioncontaining 60% active material (AM)Minoxidil 0.15 gPreservatives, complexing agent qsWater qsp 100.0 gAerosol preparation: 95.0 gAbove compositionTernary mixture of N-butane, 5.0 g55% butane and propane sold byELF AQUITANE under the trade nameAEROGAZ 3.2 N______________________________________

EXAMPLE 8
A shampoo having the following composition was prepared:

______________________________________Alkylpolyglycoside APG 500 sold by 10.0 gHORIZON CHEMICAL as an aqueoussolution containing 50% activematerial (AM)Minoxidil 0.25 gComplexing agent qsWater qsp 100.0 g______________________________________