Compositions and methods for inhibiting hair growth

Abstract

A method for inhibiting hair growth in mammals using compositions containing FP receptor antagonists (e.g., prostaglandin F analogs that are block activation of the FP receptor). The compositions can be applied topically to the skin and/or hair. The compositions can arrest hirsutism or hypertrichosis, reverse hirsutism and hypertrichosis, and further prevent hair growth. These compositions can also be used to protect hair from chemical or radiation-induced alopecia or hair loss. These compositions can also be used to inhibit pigmentation of the hair or skin.

1 - 38 . (canceled) 
     
     
         39 . A pharmaceutical composition comprising:
 A) a compound of Formula I, Formula II, or an 11-deoxy-16-fluoro PGF 2α  analog of Formula II;   B) a carrier; and   C) at least one activity enhancer selected from the group consisting of:
 i) a hair growth inhibitor selected from the group consisting of eflornithine, advanced glycation end products (AGE's), lysine, extracts of  Tetraselmis  species, fibroblast growth factor (FGF)18, cytotoxic lectin, trypsin, extract of  Juniperus  genus, malt extract, extract of ginger root, toxalbumins, inhibitors of cysteine pathway enzymes, inhibitors of nitric oxide synthetase, ornithine amino transferase inhibitors, cyclooxygenase inhibitors, and 5-lipoxygenase inhibitors; 
 ii) a hirsutism treatment agent selected from the group consisting of spironolactone, botulinum toxin, cyproterone acetate, flutamide, bicalutamide, inhibitors of 5-alpha reductase, N,N-diethyl-4-methyl-3-oxo-4-aza-5α-androstane-17β-carboxamide, PTHR1 receptor ligands, ketaconazole, estrogen receptor modulators, progesterone, estrogen, RU58841, neuropeptide Y receptor antagonists, thiazolidinedione derivatives, metformin, cyoctol (6-(5-methoxy-1-heptyl)-bicyclo (3,3,0)octan-3-one], extracts of  Serenoa repens, Epilobium  species,  Cucurbita pepo, Urtica dioica, Calluna vulgaris, Populus  species, and  Barosma  species; 
 iii) a preventative of chemotherapy-related hair loss or radiation-related hair loss; and 
 iv) a penetration enhancer; 
   
       
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of CO 2 H, C(O)NHOH, CO 2 R 1 , CH 2 OH, S(O) 2 R 1 , C(O)NHR 1 , P(O)(OR 1 ) R 2 , C(O)NHS(O) 2 R 1 , and tetrazole; 
         R 1  and R 2  are independently selected from the group consisting of a hydrogen atom, monovalent hydrocarbon groups, substituted monovalent hydrocarbon groups, aromatic groups, substituted aromatic groups, carbocyclic groups, substituted carbocyclic groups, heterogeneous groups, substituted heterogeneous groups, heterocyclic groups, substituted heterocyclic groups, heteroaromatic groups, and substituted heteroaromatic groups; 
         W is —CH 2 —, —O—, or —S(O) 2 —; and 
         X is halogen, lower alkyl, alkoxy, or hydrogen. 
       
     
     
         40 . (canceled) 
     
     
         41 . The composition of  claim 39 , wherein R 1  and R 2  are selected from the group consisting of CH 3 , C 2 H 5 , and C 3 H 7 . 
     
     
         42 . The composition of  claim 39 , wherein R is selected from the group consisting of CO 2 H, CO 2 CH 3 , C(O)NHC 2 H 5 , CO 2 C 2 H 5 , CO 2 C 3 H 7 , CO 2 C 4 H 9 , CO 2 C 3 H 7 O 2 , and C(O)NHS(O) 2 R 1 . 
     
     
         43 . The composition of  claim 42 , wherein R is selected from the group consisting of CO 2 H, CO 2 CH 3 , CO 2 C 2 H 5 , C(O)NHC 2 H 5 , and CO 2 C 3 H 7 . 
     
     
         44 . The composition of  claim 43 , wherein R is selected from the group consisting of CO 2 H, CO 2 CH 3 , C(O)NHC 2 H 5 , and CO 2 C 3 H 7 . 
     
     
         45 . The composition of  claim 39 , wherein X is methoxy. 
     
     
         46 . The composition of  claim 39 , wherein X is methyl. 
     
     
         47 . The composition of  claim 39 , wherein X is halogen. 
     
     
         48 . The composition of  claim 47 , wherein X is F. 
     
     
         49 . The composition of  claim 39  wherein the compound is the 11-deoxy-16-fluoro PGF 2α  analog. 
     
     
         50 . The composition of  claim 39 , wherein the compound is the following: 
       
         
           
           
               
               
           
         
       
     
     
         51 . The composition of  claim 39 , wherein the compound is the following: 
       
         
           
           
               
               
           
         
       
     
     
         52 . The composition of  claim 39 , wherein the compound is the following: 
       
         
           
           
               
               
           
         
       
     
     
         53 - 60 . (canceled) 
     
     
         61 . The composition of  claim 39 , wherein the activity enhancer is eflornithine. 
     
     
         62 . The composition of  claim 39 , wherein the activity enhancer is deoxyArbutin. 
     
     
         63 . The composition of  claim 39 , wherein the activity enhancer is spironolactone.