GB2191946A

GB2191946A - Stimulating hair growth

Info

Publication number: GB2191946A
Application number: GB08715313A
Authority: GB
Inventors: Jean-Francois Grollier
Original assignee: LOreal SA
Current assignee: LOreal SA
Priority date: 1986-06-30
Filing date: 1987-06-30
Publication date: 1987-12-31
Anticipated expiration: 2007-06-30
Also published as: NL8701533A; JPS6322511A; FR2600533A1; IT8767560A0; FR2600533B1; IT1211467B; BE1000401A3; DE3721563A1; GB8715313D0; CA1302287C; GB2191946B; LU86497A1; CH674931A5

Description

GB 2 191 946 A 1

SPECIFICATION

Composition for inducing and stimulating hair growth or decreasing hair loss The present invention relates to a composition for inducing and stimulating hair growth or for decreasing 5 hair loss which corn position comprises a piperidi nopyrimidine derivative.

Man has approximately 100,000 to 150,000 hai rs and it is normal to lose 50 to 100 hairs daily. The maintenance of this basic nu mber is due to the factthat the 1 ife of a hair is subject to a cycle called the pilar cycle du ring which the hair is formed grows and fails and is then replaced by a new hair which appears in the samefollicle.

In the course of a pilar cycle, three successive phases are observed, the anagen phase, the catagen phase and the telogen phase.

Du ring the f irst phase, referred to as the anagen phase, the hair passes through an active growth period associated with intense metabolic activity in the bulb region.

The second phase, referred to asthe catagen phase, istransitory and is marked by a slowing down of 15 mitotic activity. During this phase, the hair undergoes an involution,the follicle atrophies and its implantation in the skin appears increasingly shallow.

The final phase, referred to as the telogen phase, is a rest period forthe follicle and the hairfinally fails out, pushed by a newly-formed anagen hair.

This constant physical renewal process undergoes a natural change during ageing; the hair becomesfiner 20 and the cycles become shorter.

Alopecia results when this physical renewal process is accelerated or disturbed, ie the growth phases become shorter, the passage of hair into the telogen phase is earlier and hairs fall in larger numbers; successive growth cycles result in increasingly short hair, which are slowly converted into unpigmented fluff.

This phenomenon may lead to baldness.

The pilarcycle depends on manyfactors capable of leading to a more or less pronounced alopecia. Among thesefactors are nutritional factors, endocrinal factors and nervous factors. The changes in the different categories of hair may be determined with a trichogram.

Compositions which enable the effect of alopecia to be eliminated or reduced which especially enable growth to be induced orstimulated have been sought in the cosmetic and pharmaceutical industriesfor manyyears.

To this end, compounds such as 6-amino-1,2-dihydro-1 -hydroxy-2-imino-4piperidinopyrimidine and derivatives thereof have already been proposed. Such compounds are especially described in US-A-4,139,619.

A combination of retinoids with these compounds has also been proposed in WO-A-83/02,558.

Preparations based on 6-amino-1,2-dihydro-l-hydroxy-2-imino-4piperidinopyrimidine generally contain water, ethyl alcohol and propylene glycol, or mixtures of two of these compounds. However, such compositions have the disadvantage of waxing the hair, increasing its weight and making it oily and sticky.

This disadvantage is further enhanced after repeated local applications. Although such compositions have an efficacy with regard to hair growth, they are not, however, totally satisfactory from a cosmetic point of view.

We have discovered a composition which is both active in the control of alopecia and which does not substantially have the abovementioned disadvantages of the prior art compositions.

We have observed, inter alia, that a combination of certain piperidinopyrimidine derivatives with an alkylene glycol alkyl ether or dialkylene glycol alkyl ether medium, especiallythe proportions defined below, 45 enablethe bioavailai 1 ity through the skin and the activity of the active substance for hair regrowth to be increased. These properties make it possibleto achieve more quickly an efficacy with regard to activity against hair loss. This efficacy is characterized by a high ratio:

so A (number of hairs in the anagen phase) T (number of hairs in the telogen phases) Thus, inter alia, the number of applications or the concentration of the active substance may be reduced.

The composition according to the present invention, when applied, has good cosmetic properties; the hair is not waxed and is not made dull, which makes it possible to maintain the active substances in contact fora 55 longer period of time and when the treated person is active, without rinsing because of the unsightly effect of thetreatment.

The present invention accordingly provides a composition suitable for inducing and stimulating hair growth orfor decreasing hair loss, which comprises at least one compound of formula:

2 GB 2 191 946 A 2 OH 1 H2N N NH ]I N 5 inwhichillisagroupofformula R2 Y / R3 -N R4 R1 in which R3 and R4 are independently hydrogen, a lower alky], alkenyl, alkylaryl or cycloalkyi group or R3and R4together with the nitrogen to which they are attached form a heterocycle which is an aziridinyl, azetidinyl, pyrrolidinyl, piperidyl, hexahydroazepinyl, heptamethyleneimine, octamethylenelmine, morpholine or 4-(ioweralkyi)piperazinyl ring, the heterocycle optionally being substituted, on one or more carbon atoms, with oneto three lower aikyi, hydroxy or alkoxy groups and R2 is hydrogen or a lower alkyl, alkenyl, alkylalkoxy cycoalkyl, ary], arkylaryl, arylaiky], alkylarylalkyl, alkoxyarylalkyl or haloarylalkyl group, the alkyl moiety of these groups being a lower aikyl moiety, or a cosmetically acceptable addition saitthereof, in a medium comprising at least one alkylene glycol alkyl ether ordialkylene glycol alkyl ether.

In addition, the medium preferably comprisses a C2-C4 lower alcohol, especially ethyl or isopropyl alcohol, orwater or a mixture of the two.

By a "lower" group is meant a group containing, for example, 1 to 6 or preferably 1 to 4 carbon atoms.

A particularly preferred composition comprises, in addition to the derivative of Formula (1) or saitthereof, the alkylene glycol alkyl ether or dialkylene glycol alkyl ether in a proportion of from 5 to 50% byweight relative to thetotal weight of the composition and from 10 to 80% of ethyl alcohol and water byweight relative to the total weight of the composition.

Another preferred medium consists exclusively of the alkylene glycol alkyl or dialkylene glycol aikyl ether.

The particularly preferred compound of formula (1) is 6-amino-1,2-dihydro1 -hydroxy-2-imino-4-piperidino pyrimidine, which is also called "Minoxidil".

The compound of formula (1) is preferably present in the composition in a proportion of from 0.1 to 10% more preferablyfrom O.i to 5% and most preferablyform 0.5 to 5%, by weight relative to the total weight of the composition.

A particularly preferred composition contains 0.5 to 5% of 6-amino-1,2-dihydro-l-hydroxy-2-imino-4-piperidinopyrimidine in a ternary volatile vehicle comprising 10 35 to 30% of an alkyl etheror diaikylene glycol alkyl ether and 3o to 60% of ethyl alcohol, the remaining part being water,the above percentages being byweight relative to the total weight of the composition.

The preferred alkylene glycol alkyl ether or dialkylene glycol alkyl ethers are ethylene glycol monomethyl ether, propylene glycol monomethyl ether and diethylene glycol monomethyl ether.

It is observed that, once applied to the head,the medium evaporates very quickly without waxing the hair, 40 even afterseveral repeated applications.

The composition according to the present invention may, for example, be in the form of a lotion or may be pressurized as an aerosol spray in the presence of a known propellant, such as carbon dioxide, nitrogen, nitrous oxide or a volatile hydrocarbon such as butane, isobutane or propane or, preferably, a chlorinated andlorfluorinated hydrocarbon.

The reatment process for the control of hair loss mainlyconsists in applying tothe alopecic regionsofthe scalp andthe hairof an individual, a composition as defined above, for example afterwashing thescalpand the hairwith a shampoo or shortly after shampooing, the application preferably not being followed by rinsing.

This process has,ontheone hand, the features of a cosmetic process insofaras itenablesthe haironthe scalpto betreated in the cosmetic sense of theterm, ie, applying thereto substanceswhich theylackand beautifying them, and, onthe other hand,those of therapeutic treatment insofarasthe activesubstance hasa therapeutic activity relatedtothe biological mechanisms of the pilarcycle.

Thefollowing examples further illustrate the present invention.

The hair lotions are prepared:

Example 1 6-amino-1,2-dihydra-1-hydroxy-2-lmino-4piperidinopyrimidine Ethylene glycol monoethyl ether Ethyl alcohol Waterq.s.

0.5 g 10.Og 55.0 g 100.0 g 3 GB 2 191 946 A 3 After several applications of this lotion to the scalp and the hair during a treatment against hair loss, the hair does not become sticky and remains in a cosmetically satisfactory state.

Example-2

6-Amino-1,2-dihydro-1 -hydroxy-2-imino4-piperidinopyrimidine Propylene glycol monomethyl ether Ethyl alcohol Water q.s.

3.0 g 30.0 g 40.5 g 100.Og This lotion is applied as indicated in Example 1. After a treatment lasting several months, a significant increase in the ratio A f is observed, which ratio is 2.67 after one and a half months of treatment, the initial ratio being 1.39.

Example 3

6-Amino-1,2-dihydro-1 -hydroxy-2-imino 4-piperidinopyrimidine Diethylene glycol monoethyl ether 20 Ethyl alcohol Water q.s.

1.0 g 20.0 g 40.5 g 100.0 g This lotion is applied in the same way as in Example 1 and similar results are observed.

Example 4 25

The following lotion is prepared:

6-Amino-1,2-dihydro-1 -hydroxy-2-imino 4-piperidinopyrimidine 3.0 g Propylene glycol monomethyl ether 10.g Ethyl alcohol 40.5 g 30 Water q.s. 100.0 g Example 5

Thefollowing lotion is prepared:

6-Amino-1,2-dihydro-1 -hydroxy-2-imino- 35 4-piperidinopyrimidine 3.0 g Propylene glycol rnonornethyl ether 30.0 g Ethyl alcohol 40.5 g Water q.s. 100.0 g 40 Example 6

Thefollowing lotion is prepared:

6-Amino-1,2-dthydro-1 -hydroxy-2-imino 4-piperidinopyrimidine 2.0 g Propylene glycol monomethyl ether 20.0 g 45 Ethyl alcohol 50.0 g Watercl.s. 100.0 g Example 7

The following lotion is prepared: 50 6-Amino-1,2-dihydro-1 -hydroxy-2-imino 4-piperidinopyrimidine 3.0 g Propylene glycol monomethyl ether 50.0 g Ethyl alcohol 40.5 g Water q.s. 100.0 g 55 ExampleB

The following lotion is prepared:

6-Amino-1,2-dihydro-l-hydroxy-2-imino- 60 4-pi perid ino pyri midi ne 1.2 g Propylene glycol monomethyl ether q.s. 100.09 4 GB 2 191 946 A 4 Example 9 The following lotion is prepared: 6-Amino-1,2-dihydro-1 hydroxy-2-imino4-piperidi nopyri midi ne Propylene glycol monomethyl ether Ethyl alcohol q.s.

2.Og 49.09 100.09 This lotion is packaged in an aerosol container. 22 g of the above composition are pressurized inthis containerwith 78 g of a trichlorofluoromethane:dichlorodifluoromethane (61.5:38.5) mixture.

10 Example 10

The following lotion is prepared:

6-Amino-1,2-dihydro-l-hydroxy-2-imino- 4-piperidinopyrimidine 2.2 g Propylene glycol monomethyl ether 48.9 15 Watercl.s. 100.0 g Example 11

The following lotion is prepared:

6-Amino-1,2-dihydro-1 -hydroxy-2-imino- 20 4-piperidinopyrimidine 1.5 g Isopropyl alcohol 20.09 Propylene glycol monomethyl ethercl.s. 100.Og For the different compositions of Examples 4 to 11, a significant improvement is observed in skin penetration as determined in rats by percutaneous absorption. This effect is especially improved as compared with conventional compositions containing propylene glycol.

Claims

1. A composition suitable for inducing and stimulating hair growth or for decreasing hair loss, which comprises at least one compound of formula:

OH 1 35 H2N N Y NH R " N R1 40 inwhich R, is a group offormula R3 -N R4 inwhich R3 and R4are independently hydrogen, a loweralkyl, alkenyi, alkylaryl orcycloalkyl group or R3and R4, together with the nitrogen to which they are attachedjorm a heterocycle which is an aziridinyl, azetidinyi, pyrrolidinyl, piperidyl, hexahydroazepinyi, heptamethyleneimine, octamethyleneimine, morpholine or 4-(lower alkyl) piperazinyl ring, the heterocycle optionally being substituted, on one or more carbon atoms, with oneto three lower alkyl, hydroxy or alkoxy groups and R2 is hydrogen or a lower alkyl, alkeny], alkylalkoxy cycloalkyl, aryi, alkylaryl, arylalkyl, alkylarylalkyl, alkoxyarylalkyl or haloarylalkyl group, the alkyl moeity of these groups being a lower alkyl moiety, or a cosmetically acceptable addition saitthereof, in a medium comprising at least one alkylene glycol alkyl ether or dialkylene glycol alkyl ether.

2. A composition according to claim 1, in which the medium also cornrises a C2-C4 alcohol.

3. A composition according to claim 2 in which the alcohol is ethyl alcohol or isopropyl alcohol.

GB 2 191 946 A 5

4. A composition according to anyone of claims 1 to 3 which comprises water.

5. A composition is according to anyone of the claims 1 to 4 in which the medium consists of a ternary mixture of an alkylene glycol alkyl ether or dialkylene glycol alkyl ether, ethyl alcohol and water.

6. A composition according to anyone of claims 2 to 5 in which the alkylene glycol alkyl etheror dialkylene glycol al kyl ether is present in a proportion of from 5 to 50% by weight relative to the total weightof 5 thecomposition.

7. A composition according to anyone of claims 2to 6 in which the alcohol is present in a proportion of from 1 Oto 80% by weight relative to the total weight of the composition.

8. A composition according to claim 1 in which the medium consists exclusively of an alkyiene glycol alkyl ether or dialkylene glycol alkyl ether.

9. A composition according to anyone of claims 1 to 8 in which the compound of formula(0 or salt thereof is present in a proportion from 0. 1 to 10% by weight relative to the total weight of the composition.

10. A composition according to claim 9 in which the compound of formula (1) or salt thereof is present in a proportion of from 3 to 5% by weight relative to the total weight of the composition.

11. A composition according to anyone of claims 1 to 10 in which the compound formula (1) is 6-ami no-1,2-d i hydro- 1 -hyd roxy-2-i m ino-4-pi perid i nopyri midi ne.

12. A composition according to anyone of claims 1 to 11 which comprises from 0.5 to 5% of 6-am ino-1,2-dihydro-1 -hydroxy-2-imino-4-piperidinopyrimidine in a ternary volatile medium comprising 10 to 30% of anal kylene glycol al kyl ether or dial kylene glycol alkyl ether and 30 to 60% of ethyl alcohol, the remaining part being water, the above percentages being by weight relative to the total weight of the composition.

13. A composition according to anyone of claims 1 to 12, wherein the alkylene glycol alkyl ether or dialkylene glycol alkyl ether is ethylene glycol monoethyl ether, propylene glycol monomethyl ether or diethylene glycol monomethyl ether.

14. A composition according to anyone of claims 1 to 13 which is in the form of a lotion.

15. A composition according to anyone of claims 1 to 14 which is packaged in an aerosol spray in the presence of a propellant.

16. A composition substantially as hereinbefore described in anyone of the Examples.

17. A composition as defined in anyone of claims 1 to 16 for use in a therapeutic treatment of hair loss of the human or animal body.

18. A process for the cosmetic treatment of hair loss of the human or animal body in which at least one composition as defined in anyone of claims 1 to 16 is applied to the human or animal body.

19. A processfor inducing or stimulating hair growth of the human or animal body in which at least one composition as defined in anyone of claims 1 to 16 is applied to the human or animal body.

Printe d for Her Majesty's Stationery Office by Croydon Printing Company (U K) Ltd, 11187, D8991685. Published by The Patent Office, 25 Southampton Buildings, London WC2A 'I AY, from which copies maybe obtained.