MXPA01007841A - Reduction of hair growth - Google Patents

Abstract

Mammalian hair growth is reduced by applying to the skin an inhibitor of protein-tyrosine kinase. A method is described for applying to the skin a composition including an inhibitor of protein-tyrosine kinases in an amount effective to reduce hair growth. The unwanted hair growth which is reduced may be normal hair growth, or hair growth that results from an abnormal or diseased condition. The preferred composition includes at least one inhibitor of protein-tyrosine kinase in a cosmetically and/or dermatologically acceptable vehicle. The composition may be a solid, semi-solid, or liquid. The composition may be, for example, a cosmetic and dermatologic product in the form of an, for example, ointment, lotion, foam, cream, gel, or hydroalcoholic solution. The composition may also be in the form of a shaving preparation or an aftershave.

Description

REDUCTION OF HAIR GROWTH Description of the Invention The invention relates to the reduction of hair growth in mammals, particularly for cosmetic purposes. A primary function of mammal hair is to provide environmental protection. However, this function has been largely lost in humans, in whom hair is kept or removed from various parts of the body essentially for cosmetic reasons. For example, it is generally preferred to have hair on the scalp but not on the face. Various procedures have been used to remove unwanted hair, including shaving, electrolysis, depilatory creams or lotions, wax, manual hair removal, and therapeutic antiandrogens. These conventional methods generally have associated drawbacks. with them. Shaving, for example, can cause cracks and cuts, and may leave a perception of an increase in the rate of hair resurgence.

Shaving can also leave a stubbled beard (with small growth of hair) undesirable. Electrolysis, on the other hand, can keep a treated area free of hair for periods of time REF: 131712 prolonged, but can be expensive, painful, and sometimes leaves scars. Depilatory creams, although very effective, are not typically recommended for frequent use due to their high potential for irritation. Waxing and manual waxing can cause pain, discomfort, and poor eradication of short hair. Finally, antiandrogens - which have been used to treat female hirsutism - can have unwanted side effects. It has been previously stated that the rate and character of hair growth can be altered by applying inhibitors of certain enzymes to the skin. These inhibitors include inhibitors of 5-alpha reductase, ornithine decarboxylase, S-adenosylmethionine decarboxylase, gamaglutamyl transpeptidase and transglutaminase. See, for example, Breuer et al., Pat. U.S. No. 4,885,289; Shander, Pat. U.S. No. 4,720,489; Ahluwalia, Pat. U.S. No. 5,095,007; Ahluwalia et al., Pat. U.S. No. 5,096,911; and Shander et al., Pat. U.S. No. 5,132,293 '.' Protein tyrosine kinases (PTKs) are a class of enzymes that catalyze the transfer of the terminal phosphate of adenosine triphosphate (ATP) to the phenolic hydroxyl group of the amino acid tyrosine in the substrate proteins (Malarkey et al., Biochem. J. 309: 361-375, 1995). These enzymes are normally present in one of two forms, a transmembrane receptor that binds growth factors and a cytoplasmic kinase that is involved in the signal transduction of other receptors. Many transmembrane growth factor receptors possess PTK activity. The initiation of this activity after the binding of an extracellular growth factor is the first stage in the cell signal transduction pathway. The initial activation of the protein tyrosine kinase receptor is manifested by autophosphorylation after a binding of the growth factor, which could cause conformational alterations that expose the active site to external substrates. This substrate activation, in turn, transmits the signal in the direction of gene expression. The binding of epidermal growth factor (EGF) in the extracellular binding domain is an example of the signaling process .. Central to the function of protein tyrosine kinases is the recognition and binding of a nucleoside triphosphate (usually ATP) and a tyrosyl containing protein substrate. Several classes of protein kinase inhibitors have been described (Casnellie, Advances in Pharmacology 22: 167-205, 1991; Burke, Drugs of the Future 17: 119-131, 1992). These include agents that prevent the nucleotide (e.g., ATP) from binding to PTKs; which prevent the substrate from binding to the peptide bond site; and agents that reduce the catalytic efficiency by some other mechanisms, e.g., binding to the alloestheric regulatory site. The invention characterizes the reduction of unwanted hair growth in mammals (including human) - particularly the growth of androgen-stimulated hair - applying to the skin a composition that includes an inhibitor of the protein tyrosine kinases in an amount effective to reduce hair growth. The growth of unwanted hair that is reduced may be normal hair growth, or hair growth that results from an abnormal condition or disease. Other features and advantages of the invention could be apparent from the description of the modalities. preferred thereto, and the claims. The preferred composition includes at least one protein tyrosine kinase inhibitor in a cosmetic and / or dermatologically acceptable vehicle. The composition could be a solid, semi-solid or liquid. The composition could be, for example, a cosmetic or dermatological product in the form of for example, an ointment, lotion, foam, cream, gel, or hydroalcoholic solution. The composition could also be in the form of a preparation for shaving or after shaving. The vehicle itself may be inert or may possess its own cosmetic, physiological and / or pharmaceutical benefits. The tyrosine kinase protein inhibitors could interfere with the nucleotide binding site on the enzyme or the peptide binding site on the enzyme, or it could act by some other mechanism. An example of a protein tyrosine kinase inhibitor that interferes with the nucleotide binding site is lavendustine-A. (See Onoda et al.,) J. Nat. Prod., 52: 1252-1257, 1989). Examples of protein tyrosine kinase inhibitors that interfere with the peptide binding site include erbestatin (Umega et al., J. Antibiot,, 33: 170-73, 1986), which inhibits the protein tyrosine kinase of the EGF receptor; trifostins, which are erbestatin analogues (Levitzki, FASEB J. 6: 3275-3282, 1982); a certain synthetic tetrahydroxy trans-estylbenzene, or piceatanol (Geahlen, Biochem., and Biophy. Res. Commun. 165: 241-245, 1989). The following are the chemical names of specific trifostins which are inhibitors of the protein tyrosine kinase: 4-hydroxybenzylidene malononitrile (tyrophostin A8); 3,5-di-t-but-il-4-hydroxybenzylidene malononit ryl (Typhofostine A9); a-cyano- (3, 4-dihydroxy) cinnamonitrile (tyrophosphate) A23); -cyano- (3,4,5-trihydroxy) cinnamonitrile (Tyrophostin A25); α-cyano- (3,4-dihydroxy) cinnamide; (Tyrophostin A46); α-cyano- (3, 4, -dihydroxy) thiocinamide (tyrophophine A47); 2-amino-4- (4 '-hydroxyphenyl) -1, 1,3-trichlorobuta-1,3-diene (tirofostine A48); 2-amino-4- (3 ', 4', 5 '-trihydroxyphenyl) -1, 1,3-trichlorobuta-l, 3-diene (tyrophostin A51); 2-amino-4 - (lH-indol-5-yl) -1, 1,3-trichlorobuta-1,3-diene (tirofostin AG 370); 4-hydroxy-3-methoxy-5- (benzothiazoli thiomet il) benzylideneacetamide (tyrophostin 825); 4-amino-N- (2,5-dihydroxybenzyl) methyl γ-benzoate (tyropostin AG 957); a-cyano- (3,4-dihydroxy) cinnamonitrile (tirofostine AG 1288); 4- (3-chloroanilino) -6,7-dimethoxyquinazoline (tirofostin AG 1478); a-cyano- (3,4-dihydroxy) -N-benzylcinamide (tirofostin B42); (-) - R-N- (a- et il-benzyl) -3,4-dihydroxybenzylideneacetamide (tirofostine B44 (-)); α-cyano- (3, -dihydroxy) -N- (3-phenylpropyl) cinnamide (tyrophostin B46); (Tyrofostin B48; α-cyano- (3,4-dihydroxy) -N-phenyl-amide; α-cyano- (+) - (S) - (N) - (α-phenethyl) - (3,4-dihydroxy) cinnamide (tyrophostin B50 (+)) and a-cyano- (3, -dihydroxy) -N- (phenylbutyl) cinnamide (tyrophostin B56) Examples of protein tyrosine kinase inhibitors that work by some other mechanism include the benzoquinone ansamycin herbimycin A. Inactivation by this inhibitor involves the steric hindrance of the active site rather than the destruction of the catalytic activity per se Additional inhibitors include thiazolidin-diones, phenazocine, 2,3-dihydro-2-thioxo-lH-indole acids -3-alkanoics and their dimeric oxidation products, 2, 2'-dithiobis (1H) -indol-3-alkanoic acids) and sui fonylbenzoyl-ni t roestirenes (Thompson et al., J. Med. Chem. 36: 2459-2469, 1993; Thompson et.al., J. Med. Chem. 37: 598-609, 1994; and Traxler et.al., J. Med. Chem. 34: 2328-2337, 1991). The composition could include more than one protein tyrosine kinase inhibitor. In addition, the composition could include one or more other types of hair growth reducing agents, such as those described in Pat. U.S. No. 4,885,289; Pat. U.S. No.4, 720, 489; Pat. U.S. No. 5,132,293; Pat. U.S. No. 5,096,911; Pat. U.S. No. 5,095,007; Pat. U.S. No.5, 143, 925; Pat. U.S. No. 5,328,686; Pat. U.S. No. 5,440,090; Pat. 'U.S. No. 5,364,885; Pat. U.S. Do not. , 417, 991 Pat. U.S. No. 5,648,394; Pat. U.S. No. 5, 468, 476 Pat. U.S. No. 5,475,763; Pat. U.S. No. 5, 554, 608 Pat. U.S. No. 5,674,477; Pat. U.S.

No.5, 728, 736; Pat. U.S. No. 5,652,273; WO 94/27586; WO 94/27563; and WO 98/03149, all of which are incorporated herein by reference. The concentration of the protein tyrosine kinase inhibitor in the composition could be varied over a wide range to a saturated solution, preferably from 0.1% to 30% by weight or even more; The reduction in hair growth increases as the amount of inhibitor applied per unit area of the skin increases. The maximum amount actually applied is limited only by the speed at which the inhibitor penetrates the skin. Effective amounts could vary, for example, from 10 to 3000 micrograms or more per square centimeter of skin. The vehicles can be formulated with liquid or solid emollients, solvents, thickeners, humectants and / or powders. Emollients include tearilic alcohol, mink oil, cetyl alcohol, oleic alcohol, isopropyl laurate, polyethylene glycol, olive oil, petrolatum, palmitic acid, oleic acid, and myristyl myristate. The solvents could include ethyl alcohol, isopropanol, acetone, diethylene glycol, ethylene glycol, dimethyl sulfoxide, and dimethylformamide.

The composition could also include components that improve the penetration of protein tyrosine kinase inhibitors into the skin and / or site of action. Examples of penetration enhancers include urea, polyoxyethylene ethers, terpenes, cis-fatty acids (oleic acid, palmitoleic acid), acetone, laurocapramo, dimethylsulfoxide, 2-pyrrolidone, oleyl alcohol, glyceryl-3-stearate, cholesterol, isopropyl ester of acid myristic, and propylene glycol. The composition can also be formulated to provide a reserve in or on the surface of the skin to provide a continuous slow release of the inhibitor. The composition could also be formulated to slowly evaporate from the skin, allowing additional time for the inhibitor to penetrate the skin. The following are examples of compositions that include a protein tyrosine kinase inhibitor.

EXAMPLE 1 A . composition contains 10% by weight of a protein tyrosine kinase inhibitor and 90% by weight of a vehicle containing water (68% vehicle by weight), ethanol (16% vehicle by weight), propylene glycol (5% by weight) vehicle in weight), dipropylene glycol (5% of the vehicle by weight), benzyl alcohol (4% of the vehicle by weight) and propylene carbonate (2% of the vehicle by weight). The inhibitor can be, for example, a tirofostin, erbestatin, lavendustine A, methyl caffeate, Herbimycin A, tris acetoxymethyl ester of HNMPA (AM) 3-hydroxy-2-naphthalenylmethylphosphonic acid or N-acetyl-Asp-Tyr- (2) -malonil) -Val-Pro-Met-Leu-NH2.

EXAMPLE 2 A second composition contains 10% by weight of a protein tyrosine kinase inhibitor and 90% by weight of a vehicle containing water (80.84% by weight of the vehicle), glyceryl stearate (4.24% by weight of the vehicle), 100% by weight. - polyethylene glycol esterreate (4.09% by weight of the vehicle), cetearyl alcohol (3.05% by weight of the vehicle), ceteareht-20 (2.5% by weight of the vehicle), mineral oil (2.22% by weight of the vehicle), stearyl alcohol (1.67% by weight of the vehicle), and dimethicone (0.56% by weight of the vehicle). The inhibitor can be, for example, a tirofostin, erbestatin, lavenderustine A, methyl caffeine, herbimycin A, tris acetoxymethyl ester of HNMPA (AM) 3-hydroxy-2-naphthalenylmethylphosphonic acid, or N-acetyl-Asp-Tyr- (2-malonyl) -Val-Pro-Met-Leu NH2. Optionally, "one of the aforementioned penetration improvers could be added to the composition.A penetration enhancer could be added at concentrations of, for example, 0.13% to 20% by weight.The preferred concentration is 0.5% to 5% by weight. The composition should be applied topically to a selected area of the body from which it is desired to reduce hair growth., the composition can be applied to the face, particularly to the part of the face beard, i.e., the cheeks, neck, upper lip, and chin. The composition could also be used as an auxiliary to other methods of hair eradication including shaving, waxing, mechanical hair removal, chemical hair removal, electrolysis and hair removal supported by the laser. The composition can also be applied to the legs, arms, torso and armpits. The composition is particularly suitable for reducing the growth of unwanted hair in women suffering from hirsutism or other conditions. In humans, the composition should be applied once or twice a day, or even more frequently, to achieve a noticeable reduction in hair growth. The perception of reduced hair growth could occur as early as 24 hours or 48 hours (eg, between normal shaving intervals) after use or it could take up to, say, three months. The reduction in hair growth is demonstrated when, for example, the speed of hair growth is decreased, the need for removal is reduced, the subject perceives less hair at the treated site, or quantitatively, when hair weight is reduced. eradicated (ie, hair mass).

PROOF OF PILOUS FOLLICULAR GROWTH IN HUMAN The hair follicles of humans were isolated in the growth phase (anagen) of tissue raised from face under a dissecting sphere using a scalpel and watchmaker's forceps. The skin was divided into thin strips exposing 2-3 rows of follicles that could be easily dissected. The follicles were placed in 0.5 mL Williams E medium (Life Technologies, Gaithersburg, MD) supplemented with 2 mm of L-glutamine, 10 μg / mL of insulin, 10 ng / mL of hydrocortisone, 100 units of penicillin, 0.1 mg / mL of streptomycin and 0.25 μg / mL of amphotericin B. The follicles were incubated in 24-well plates (1 follicle / well) at 37 ° C in an atmosphere of 5% C02 and 95% air. Hair follicles were videotaped on 24-well plates under the dissection sphere under 20x power. The lengths of the hair follicles were evaluated using a program of elements (software) for image analysis (Computer Eyes and NIH Image). Typically, initial recordings were made on day 0 (the day the follicles were placed in the culture), and on days 1, 4, and 7.

INHIBITION OF HAIR GROWTH IN HUMAN The effect of five protein tyrosine kinase inhibitors on follicular growth of human hair was determined by exposing the isolated follicles to the inhibitors of the enzyme. The hair follicle lengths were determined before and after the inhibitor treatment. Typically, a group of 12 isolated follicles was used to determine the effect of each inhibitor on hair follicle growth. The reduction of hair follicle growth in the range of 40 to 100% was observed; The results are shown in Table 1.

TABLE 1 The test described above will be referred to herein as the "Growth Test of the Human Hair Follicle." Preferred compositions provide a reduction in hair growth of at least about 10%, more preferably at least about 40%, and more preferably at least approximately 70%.

In another experiment, isolated hair follicles were exposed to either 1 mM or 0.01 mM erbestatin concentration of the protein tyrosine kinase inhibitor, and the hair growth rate was compared to the control. Measurements were taken on days 0, 1 and 4. The results are as shown in Table 2.

TABLE 2 PROOF OF THE TIROSINE KINASE PROTEIN The protein tyrosine kinase activity was measured in human skin samples rich in sharp follicles using a commercially available test kit (Calbiochem). The human skin obtained by a local plastic surgeon as a byproduct of the face lift procedures was homogenized into four volumes of the extraction buffer containing 20 mM Tris-HCl, pH 7.4, 50 M NaCl, 1 mM EDTA, EGTA 1 mM, 5 mM mercaptoethanol. The samples were centrifuged for 10 min at 16,000 x g to remove the membrane / organelle fractions. The supernatant fraction was used for the tyrosine kinase test. By adding 25 ml of the 20X concentrated solution to 475 ml of deionized water and mixing, a working solution of the washing plate buffer was made. The kinase buffer was prepared by adding 50 ul / ml of the stock solution of 2 mM ATP to the sample buffer IX without 2-mercaptoethanol. (90 ul of the kinase buffer / well). For the enzyme test, 10 ul of each sample was added to a well. 10 ul of standard Abl were added as positive controls to a well. The kinase reaction was started by adding 90 ul of the kinase buffer / well and incubated at room temperature for 30 minutes. The contents of each well were washed six times with wash buffer IX, 100 ul of the PY20 antibody diluted 1: 200 was added with the sample reaction buffer / kinase IX (without ATP) (15 ul to 3 ml) and the combination it was incubated for 30 minutes. The test solutions were washed with the wash buffer, and 100 ul of substrate solution was added to each and incubated in the dark for 6 minutes. 100 ul of stop solution was added, and the UV absorbance reading at 450 nm was read. The increase in UV absorbance at 450nm provided a measure of the enzymatic activity. The ability of protein tyrosine kinase inhibitors to inhibit the skin / hair follicle enzymatic activity was determined by measuring the activity of the protein tyrosine kinase in the presence and absence of the inhibitor. For enzyme inhibition studies, the inhibitor was added to the reaction mixture at a concentration of 1 mM after the addition of the enzyme sample. The results are shown in Table 3.

TABLE 3 HNMPA (AM) 3: hydroxy-2-naphthalenylmethylphosphonic acid tris acetoxymethyl ester Other modalities are within the claims It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (59)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. A method for reducing hair growth in mammals, characterized in that it comprises selecting an area of skin from which it is desired to reduce hair growth; applying to the skin area a dermatologically acceptable composition comprising a protein tyrosine kinase inhibitor in an amount effective to reduce hair growth.

2. The method according to claim 1, characterized in that the protein tyrosine kinase is an EGF receptor.

3. The method according to claim 1, characterized in that the inhibitor is lavendustine-A.

4. The method according to claim 1, characterized in that the inhibitor is erbestatin.

5. The method according to claim 1, characterized in that the inhibitor is a trifostine.

6. The method according to claim 1, characterized in that the inhibitor is piceatanol.

7. The method according to claim 1, characterized in that the inhibitor is 4-hydroxybenzylidene malonium trile.

8. The method according to claim 1, characterized in that the inhibitor is 3,5-di-t-butyl-4-hydroxy-benzylidenemalonium trile.

9. The method according to claim 1, characterized in that the inhibitor is a-cyano-3-dihydroxy) cinamonitrile.

10. The method according to claim 1, characterized in that the inhibitor is a-cyano- (3,, 5-dihydroxy) cinnamonitrile.

The method according to claim 1, characterized in that the inhibitor is a-cyano- (3,4-dihydroxy) cinnamide.

The method according to claim 1, characterized in that the inhibitor is α-cyano- (3,4, -dihydroxy) thiocinamide.

13. The method according to claim 1, characterized in that the inhibitor is 2-amino-4- (4'-hydroxyphenyl) -1, 1,3-tricianobuta-l, 3-diene.

14. The method according to claim 1, characterized in that the inhibitor is 2-amino-4- (3 ', 4', 5 '-trihydroxyphenyl) -1, 1,3-tricianobuta-l, 3-dimo.

15. The method according to claim 1, characterized in that the inhibitor is 2-amino-4 - (1HA-indol-5-yl) -1, 1,3-tricianobuta-l, 3-diene.

16. The method according to claim 1, characterized in that the inhibitor is 4-hydroxy-3-methoxy-5- (benzothiazolylthiomethyl) benzylideneacetamide.

17. The method according to claim 1, characterized in that the inhibitor is 4-amino-N- (2,5-dihydroxybenzyl) methyl benzoate.

18. The method according to claim 1, characterized in that the inhibitor is a-cyano- (3,4-dihydroxy) cinnamonitrile.

19. The method according to claim 1, characterized in that the inhibitor is 4- (3-chloroanilino) -6,7-dimethoxyquinazoline.

20. The method according to claim 1, characterized in that the inhibitor is a-cyano- (3,4-dihydroxy) -N-benzylcinnamide.

21. The method according to claim 1, characterized in that the inhibitor is (-) - R-N- (α-methylbenzyl) -3,4-dihydroxybenzylideneacetamide.

22. The method in accordance with the claim 1, characterized in that the inhibitor is α-cyano- (3,4-dihydroxy) -N- (3-phenylpropyl) cinnamide.

23. The method according to claim 1, characterized in that the inhibitor is a-cyano- (3,4-dihydroxy) -N-phenyl-amide.

24. The method of compliance with the claim 1, characterized in that the inhibitor is α-cyano- (+) - (S) -N- (α-phenethyl) - (3, -dihydroxy) cinnamide.

25. The method of compliance with the claim 1, characterized in that the inhibitor is α-cyano- (3,4-dihydroxy) -N- (phenylbutyl) cinnamide.

26. The method of compliance with the claim 1, characterized in that the inhibitor is herbimycin A.

27. The method according to the claim 1, characterized in that the inhibitor is thiazolidin-diones.

28. The method of compliance with the claim 1, characterized in that the inhibitor is phenazocine.

29. The method of compliance with the claim 1, characterized in that the inhibitor is a 2,3-dihydro-2-thioxo-lH-indol-3-alkanoic acid.

30. The method according to claim 1, characterized in that the inhibitor is a 2,2'-dithiobis (lH-indol-3-alkanoic acid).

31. The method according to claim 1, characterized in that the inhibitor is a sulfonylbenzoyl-nitrostyrenes.

32. The method according to claim 1, characterized in that the inhibitor is methyl caffeate.

33. The method according to claim 1, characterized in that the inhibitor is HNMPA (AM) 3.

34. The method according to claim 1, characterized in that the concentration of the inhibitor of the composition is between 0.1% and 30%.

35. The method according to claim 1, characterized in that the inhibitor provides a reduction in hair growth of at least 20% when tested in the Human Hair Follicle Growth test.

36. The method according to claim 1, characterized in that the inhibitor provides a reduction in hair growth of at least 70% when tested in the Human Hair Follicle Growth Test.

37. The method according to claim 1, characterized in that the inhibitor is applied to the skin in an amount of 10 to 3000 micrograms of the inhibitor per square centimeter of skin.

38. The method according to claim 1, characterized in that the mammal is a human.

39. The method of compliance with the claim 38, characterized in that the skin area is on the face of the human.

40. The method of compliance with the claim 39, characterized in that the composition is applied to the skin area in combination with shaving.

41. The method according to claim 38, characterized in that the skin area is on one leg of the human.

42. The method according to claim 38, characterized in that the skin area is on an arm of the human.

43. The method according to claim 38, characterized in that the skin area is on the human's armpit.

44. The method according to claim 38, characterized in that the skin area is on the torso of the human.

45. The method according to claim 1, characterized in that it is applied to an area of the skin of a woman suffering from hirsutism.

46. The method according to claim 1, characterized in that the hair growth comprises hair growth stimulated with androgen.

47. The method according to claim 1, characterized in that the composition further includes a second component that also causes a reduction in hair growth.

48. A method for reducing hair growth in mammals, characterized in that it comprises: selecting an area of skin from which it is desired to reduce hair growth, the skin area includes the protein tyrosine kinase; and inhibit protein tyrosine kinase sufficiently to cause a reduction in hair growth.

49. A method according to any of claims 1 to 48, characterized in that the application of the inhibitor has a cosmetic effect.

50. The use of a protein tyrosine kinase inhibitor for the manufacture of a medicament, characterized in that it inhibits the growth of hair in mammals.

51. The use according to claim 50, characterized in that the inhibitor is as defined in any of claims 1 to 33.

52. A method for producing a composition for inhibiting hair growth in mammals, characterized in that it comprises selecting an inhibitor of protein tyrosine kinase, and combine the inhibitor, in an effective amount to reduce hair growth, with vehicle or carrier non-toxic, dermatologically acceptable.

53. A method according to claim 52, characterized in that the vehicle or carrier is adapted to spread on the skin of a mammal.

54. A method according to the indication 52 or 53, characterized in that a cosmetic composition is produced.

55. A method according to the rei indication 52, characterized in that the inhibitor is as defined in any of claims 1 to 33.

56. The new use of a protein tyrosine kinase inhibitor, characterized in that it reduces hair growth. .

57. A composition when used to inhibit hair growth in mammals, characterized in that it includes a protein tyrosine kinase inhibitor in an amount effective to reduce hair growth and a non-toxic, dermatologically acceptable carrier or carrier.

58. A composition according to claim 57, characterized in that the inhibitor is as defined in any of claims 1 to 33.

59. A composition according to claim 57 or 58, characterized in that it is a cosmetic composition.