Methods, Kits, and Compositions for Generating New Hair Follicles and Growing Hair

Abstract

The invention features methods, kits, and compositions for generating new hair follicles and growing hair on a subject.

1 . A composition comprising from 0.00001% to 0.5% (w/v) of a small molecule EGFR inhibitor formulated for topical administration, wherein said EGFR inhibitor is a non-naturally occurring nitrogen-containing heterocycle of less than about 2,000 daltons, or a metabolite thereof. 
     
     
         2 . The composition of  claim 1 , further comprising a pharmaceutically acceptable excipient selected from an antioxidant, a emulsifying excipient, a gelling agent, a hydrocolloid, a cross-linking agent, and a plasticizer. 
     
     
         3 . The composition of  claim 2 , wherein said pharmaceutically acceptable excipient is an antioxidant selected from the group consisting of thiols, sulphoximines, metal chelators, fatty acids, vitamins, phenols, stilbenes, uric acid, mannose, selenium, and propyl gallate. 
     
     
         4 . The composition of  claim 1 , wherein said EGFR inhibitor is present at a concentration from 0.001% to 0.1% (w/v). 
     
     
         5 . The composition of  claim 1 , wherein said pharmaceutically acceptable excipient is an emulsifying excipient selected from the group consisting of polyethoxylated fatty acids, PEG-fatty acid diesters, PEG-fatty acid mono-ester and di-ester mixtures, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglycerized fatty acids, propylene glycol fatty acid esters, mixtures of propylene glycol esters-glycerol esters, mono- and diglycerides, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugar esters, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, lower alcohol fatty acid esters, ionic surfactants, tocopherol esters, and sterol esters. 
     
     
         6 . The composition of  claim 2 , wherein said pharmaceutically acceptable excipient is a gelling agent. 
     
     
         7 . The composition of  claim 2 , wherein said pharmaceutically acceptable excipient is a hydrocolloid. 
     
     
         8 . The composition of  claim 2 , wherein said pharmaceutically acceptable excipient is a cross-linking agent. 
     
     
         9 . The composition of  claim 2 , wherein said pharmaceutically acceptable excipient is a plasticizer. 
     
     
         10 . The composition of  claim 1 , further comprising an additional biologically active agent selected from an antihistamine, an anti-inflammatory, a retinoid, an anti-androgen, an immunosuppressant, a channel opener, an antibiotic, and an antimicrobial. 
     
     
         11 . The composition of  claim 10 , wherein said additional biologically active agent is an antihistamine selected from the group consisting of mepyramine, diphenhydramine, and antazoline. 
     
     
         12 . The composition of  claim 10 , wherein said additional biologically active agent is an anti-inflammatory selected from the group consisting of corticosteroids, NSAIDs, and COX-2 inhibitors. 
     
     
         13 . The composition of  claim 10 , wherein said additional biologically active agent is a retinoid selected from the group consisting of 13-cis-retinoic acid, adapalene, all-trans-retinoic acid, and etretinate. 
     
     
         14 . The composition of  claim 10 , wherein said additional biologically active agent is an anti-androgen selected from the group consisting of finasteride, flutamide, diazoxide, 11alpha-hydroxyprogesterone, ketoconazole, RU58841, dutasteride, fluridil, and QLT-7704. 
     
     
         15 . The composition of  claim 10 , wherein said additional biologically active agent is an immunosuppressant selected from the group consisting of cyclosporine, tacrolimus, rapamycin, everolimus, and pimecrolimus. 
     
     
         16 . The composition of  claim 10 , wherein said additional biologically active agent is a channel opener selected from the group consisting of minoxidil, diazoxide, and phenyloin. 
     
     
         17 . The composition of  claim 10 , wherein said additional biologically active agent is an antimicrobial selected from the group consisting of benzyl benzoate, benzalkonium chloride, benzoic acid, benzyl alcohol, butylparaben, ethylparaben, methylparaben, propylparaben, camphorated metacresol, camphorated phenol, hexylresorcinol, methylbenzethonium chloride, cetrimide, chlorhexidine, chlorobutanol, chlorocresol, cresol, glycerin, imidurea, phenol, phenoxyethanol, phenylethylalcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, sodium benzoate, sodium proprionate, sorbic acid, and thiomersal. 
     
     
         18 . The composition of  claim 1 , further comprising an anti-androgen and a channel opener. 
     
     
         19 . The composition of  claim 18 , wherein said anti-androgen is finasteride and said channel opener is minoxidil. 
     
     
         20 . The composition of  claim 1 , wherein said composition is formulated as a cream, lotion, stick, ointment, gel, spray, foam, patch, aerosol, wound dressing, or drop. 
     
     
         21 . The composition of  claim 1 , wherein said small molecule EGFR inhibitor is selected from leflunomide, gefitinib, erlotinib, lapatinib, canertinib, vandetanib, CL-387785, PKI166, pelitinib, HKI-272, and HKI-357. 
     
     
         22 . The composition of  claim 21 , wherein said small molecule EGFR inhibitor is gefitinib. 
     
     
         23 . The composition of  claim 21 , wherein said small molecule EGFR inhibitor is erlotinib. 
     
     
         24 . The composition of  claim 21 , wherein said small molecule EGFR inhibitor is leflunomide. 
     
     
         25 . The composition of  claim 1 , wherein said small molecule EGFR inhibitor is the leflunomide metabolite A771726. 
     
     
         26 . A kit comprising (i) a composition comprising from 0.000001% to 10% (w/v) of a small molecule EGFR inhibitor formulated for topical administration, wherein said EGFR inhibitor is a non-naturally occurring nitrogen-containing heterocycle of less than about 2,000 daltons, or a metabolite thereof; and (ii) instructions for applying said composition to the skin of a subject in need of generating a hair follicle or stimulating a hair growth. 
     
     
         27 . A kit comprising (i) the composition of  claim 1 ; and (ii) instructions for applying said composition to the skin of a subject. 
     
     
         28 . The kit of  claim 27 , further comprising instructions for applying said composition to the head of a subject. 
     
     
         29 . The kit of  claim 27 , wherein said subject is in need of generating a hair follicle or stimulating a hair growth. 
     
     
         30 . The kit of  claim 27 , further comprising instructions for applying said composition to the skin of a subject once or twice daily. 
     
     
         31 . The kit of  claim 30 , further comprising instructions for applying said composition to the skin of a subject for at least 2 consecutive days. 
     
     
         32 . The kit of  claim 31 , further comprising instructions for applying said composition to the skin of a subject for at least 5 consecutive days. 
     
     
         33 . The kit of  claim 27 , wherein said skin has undergone reepithelialization less than two weeks prior to the first administration of said composition. 
     
     
         34 . The composition of  claim 3 , wherein said metal chelator is selected from the group consisting of α-hydroxy-fatty acids, palmitic acid, phytic acid, lactoferrin, citric acid, lactic acid, and malic acid, humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA, and DTPA. 
     
     
         35 . The kit of  claim 27  wherein said small molecule EGFR inhibitor is selected from leflunomide, gefitinib, erlotinib, lapatinib, canertinib, vandetanib, CL-387785, PKI166, pelitinib, HKI-272, and HKI-357. 
     
     
         36 . The kit of  claim 35 , wherein said small molecule EGFR inhibitor is gefitinib. 
     
     
         37 . The kit of  claim 35 , wherein said small molecule EGFR inhibitor is erlotinib. 
     
     
         38 . The kit of  claim 35 , wherein said small molecule EGFR inhibitor is leflunomide. 
     
     
         39 . The kit of  claim 27 , wherein said small molecule EGFR inhibitor is the leflunomide metabolite A771726. 
     
     
         40 . A kit comprising a composition formulated for topical administration comprising (i) a small molecule EGFR inhibitor selected from leflunomide, gefitinib, erlotinib, lapatinib, canertinib, vandetanib, CL-387785, PKI166, pelitinib, HKI-272, and HKI-357; and (ii) an additional biologically active agent selected from an antihistamine, an anti-inflammatory, a retinoid, an anti-androgen, an immunosuppressant, a channel opener, an antibiotic, and an antimicrobial. 
     
     
         41 . The kit of  claim 40 , wherein said small molecule EGFR inhibitor is gefitinib or erlotinib and said additional biologically active agent is a channel opener selected from minoxidil, diazoxide, and phenyloin. 
     
     
         42 . The kit of  claim 40 , wherein said composition is formulated as a cream, lotion, stick, ointment, gel, spray, foam, patch, aerosol, wound dressing, or drop. 
     
     
         43 . The kit of  claim 27 , further comprising instructions for administering said composition at night. 
     
     
         44 . The kit of  claim 27 , further comprising instructions for administering said composition during the day. 
     
     
         45 . A method for generating a hair follicle or stimulating a hair growth on the skin of a subject, said method comprising the steps of:
 (a) inducing reepithelialization of the skin of said subject; and   (b) contacting the cells of said skin with the composition of  claim 1 .   
     
     
         46 . The method of  claim 45 , wherein said small molecule EGFR inhibitor is selected from leflunomide, gefitinib, erlotinib, lapatinib, canertinib, vandetanib, CL-387785, PKI166, pelitinib, HKI-272, and HKI-357.