Compositions and methods for treating hair loss using non-naturally occurring prostaglandins

Abstract

A method for treating hair loss in mammals uses compositions containing prostaglandin F analogs. The compositions can be applied topically to the skin. The compositions can arrest hair loss, reverse hair loss, and promote hair growth.

1 . A composition for treating hair loss comprising:
 A) an active ingredient selected from the group consisting of a prostaglandin F analog having a structure selected from the group consisting of   
       
         
           
           
               
               
           
         
       
       pharmaceutically acceptable salts and hydrates of the structures above; biohydrolyzable amides, esters, and imides of the structures above; optical isomers, diastereomers, and enantiomers of the structures above; and combinations thereof,
 wherein R 1  is selected from the group consisting of C(O)NHOH and C(O)NHS(O) 2 R 4 ; 
 R 2  is selected from the group consisting of a hydrogen atom, a lower heterogenous group, and a lower monovalent hydrocarbon group; 
 R 3  is selected from the group consisting of a monovalent hydrocarbon group, a heterogeneous group, a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted monovalent hydrocarbon group, a substituted heterogeneous group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; 
 R 4  is selected from the group consisting of a monovalent hydrocarbon group, a heterogeneous group, a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted monovalent hydrocarbon group, a substituted heterogeneous group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; 
 X is selected from the group consisting of —C═C—, a covalent bond, —CH═C═CH—, —CH═CH—, —CH═N—, —C(O)—, —C(O)Y—, —(CH 2 ) n —, wherein n is 2 to 4, —CH 2 NH—, —CH 2 S—, and —CH 2 O—; 
 Y is selected from the group consisting of an oxygen atom, a sulfur atom, and NH; and 
 Z is selected from the group consisting of a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; and 
 B) a carrier. 
 
     
     
         2 . (canceled) 
     
     
         3 . The composition of  claim 1 , wherein R 2  is a hydrogen atom. 
     
     
         4 . The composition of  claim 1 , wherein R 3  is selected from the group consisting of methyl, ethyl, and isopropyl. 
     
     
         5 . The composition of  claim 1 , wherein R 4  is a phenyl group. 
     
     
         6 . The composition of  claim 1 , wherein X is a covalent bond and Z is selected from the group consisting of an aromatic ring, a heteroaromatic ring, a substituted aromatic ring, and a substituted heteroaromatic ring. 
     
     
         7 . The composition of  claim 1 , wherein X is —C═C—, and Z is a monocyclic aromatic ring. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . A method of growing hair, wherein the method comprises topically applying to mammalian skin a safe and effective amount of a composition comprising:
 A) an active ingredient selected from the group consisting of a prostaglandin F analog having a structure selected from the group consisting of   
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof;
 wherein R 1  is selected from the group consisting of C(O)NHOH, C(O)NHS(O) 2 R 4 , and tetrazole; 
 R 2  is selected from the group consisting of a hydrogen atom, a lower heterogenous group, and a lower monovalent hydrocarbon group; 
 R 3  is selected from the group consisting of a monovalent hydrocarbon group, a heterogeneous group, a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted monovalent hydrocarbon group, a substituted heterogeneous group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; 
 R 4  is selected from the group consisting of a monovalent hydrocarbon group, a heterogeneous group, a carbocyclic group, a heterocyclic group, an aromatic group. a heteroaromatic group, a substituted monovalent hydrocarbon group, a substituted heterogeneous group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; 
 X is selected from the group consisting of —C═C—, a covalent bond, —CH═C═CH—, —CH═CH—, —CH═N—, —C(O)—, —C(O)Y—, —(CH 2 ) n —, wherein n is 2 to 4, —CH 2 NH—, —CH 2 S—, and —CH 2 O—; 
 Y is selected from the group consisting of a sulfur atom, an oxygen atom, and NH; and 
 Z is selected from the group consisting of a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group. 
 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 16 , wherein R 2  is a hydrogen atom. 
     
     
         19 . The method of  claim 16 , wherein R 3  is selected from the group consisting of methyl, ethyl, and isopropyl. 
     
     
         20 . The method of  claim 16 , wherein R 4  is a phenyl group. 
     
     
         21 . The method of  claim 16 , wherein X is a covalent bond and Z is selected from the group consisting of an aromatic ring, a heteroaromatic ring, a substituted aromatic ring, and a substituted heteroaromatic ring. 
     
     
         22 . The method of  claim 16 , wherein X is —C═C—, and Z is a monocyclic aromatic ring. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 16 , wherein the composition is a topical composition in a form selected from the group consisting of solutions, oils, creams, ointments, gels, lotions, shampoos, leave-on and rinse-out hair conditioners, milks, cleansers, moisturizers, sprays, and skin patches. 
     
     
         25 . The method of  claim 16 , wherein the composition is a topical composition further comprising B) a carrier, wherein the carrier is selected from the group consisting of water, alcohols, aloe vera gel, allantoin, glycerin, vitamin A and E oils, mineral oil, propylene glycol, dimethyl isosorbide, polypropylene glycol-2 myristyl propionate, and combinations thereof. 
     
     
         26 . The method of  claim 16 , wherein the composition further comprises C) an activity enhancer selected from the group consisting of i) a hair growth stimulant, ii) a penetration enhancer, and combinations thereof. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 26 , wherein component ii) is selected from the group consisting of 2-methyl propan-2-ol, propan-2-ol, ethyl-2-hydroxypropanoate, hexan-2,5-diol, polyoxyethylene(2) ethyl ether, di(2-hydroxypropyl) ether, pentan-2,4-diol, acetone, polyoxyethylene(2) methyl ether, 2-hydroxypropionic acid, 2-hydroxyoctanoic acid, propan-1-ol, 1,4-dioxane, tetrahydrofuran, butan-1,4-diol, propylene glycol dipelargonate, polyoxypropylene 15 stearyl ether, octyl alcohol, polyoxyethylene ester of oleyl alcohol, oleyl alcohol, lauryl alcohol, dioctyl adipate, dicapryl adipate, di-isopropyl adipate, di-isopropyl sebacate, dibutyl sebacate, diethyl sebacate, dimethyl sebacate, dioctyl sebacate, dibutyl suberate, dioctyl azelate, dibenzyl sebacate, dibutyl phthalate, dibutyl azelate, ethyl myristate, dimethyl azelate, butyl myristate, dibutyl succinate, didecyl phthalate, decyl oleate, ethyl caproate, ethyl salicylate, isopropyl palmitate, ethyl laurate, 2-ethyl-hexyl pelargonate, isopropyl isostearate, butyl laurate, benzyl benzoate, butyl benzoate, hexyl laurate, ethyl caprate, ethyl caprylate, butyl stearate, benzyl salicylate, 2-hydroxypropanoic acid, 2-hydroxyoctanoic acid, dimethyl sulphoxide, N,N-dimethyl acetamide, N,N-dimethyl formamide, 2-pyrrolidone, l-methyl-2-pyrrolidone, 5-methyl-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone, 1-ethyl-2-pyrrolidone, phosphine oxides, sugar esters, tetrahydrofurfural alcohol, urea, diethyl-m-toluamide, l-dodecylazacyloheptan-2-one, and combinations thereof. 
     
     
         29 . The method of  claim 16 , wherein the composition is a topical composition locally administered on the skin once per day. 
     
     
         30 . The method of  claim 29 , wherein the composition is administered once per day for 6 to 12 weeks. 
     
     
         31 . A mascara composition comprising:
 A) an active ingredient selected from the group consisting of a prostaglandin F analog having a structure selected from the group consisting of   
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof;
 wherein R 1  is selected from the group consisting of C(O)NHOH, —C(O)NHS(O) 2 R 4  and tetrazole; 
 R 2  is selected from the group consisting of a hydrogen atom, a lower heterogenous group, and a lower monovalent hydrocarbon group; 
 R 3  is selected from the group consisting of a monovalent hydrocarbon group, a heterogeneous group, a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted monovalent hydrocarbon group, a substituted heterogeneous group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; 
 R 4  is selected from the group consisting of a monovalent hydrocarbon group, a heterogeneous group, a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted monovalent hydrocarbon group, a substituted heterogeneous group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; 
 X is selected from the group consisting of —C═C—, a covalent bond, —CH═C═CH—, —CH═CH—, —CH═N—, —C(O)—, —C(O)Y—, —(CH 2 ) n —, wherein n is 2 to 4, —CH 2 NH—, —CH 2 S—, and —CH 2 O—; 
 Y is selected from the group consisting of an oxygen atom, a sulfur atom, and NH; and 
 Z is selected from the group consisting of a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted carbocyclic group. a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; 
 dd) a water-insoluble material, 
 ee) a water-soluble, film-forming polymer, 
 ff) a wax; 
 o) a surfactant; 
 gg) pigment; and 
 s) a solvent. 
 
     
     
         32 . A method for darkening and thickening hair comprising applying to growing hair and skin, a safe and effective amount of a composition comprising:
 A) an active ingredient selected from the group consisting of a prostaglandin F analog having a structure selected from the group consisting of   
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof;
 wherein R 1  is selected from the group consisting of —C(O)NHS(O) 2 R 4  and tetrazole; 
 R 2  is selected from the group consisting of a hydrogen atom, a lower heterogenous group, and a lower monovalent hydrocarbon group; 
 R 3  is selected from the group consisting of a monovalent hydrocarbon group, a heterogeneous group, a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted monovalent hydrocarbon group, a substituted heterogeneous group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; 
 R 4  is selected from the group consisting of a monovalent hydrocarbon group, a heterogeneous group, a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted monovalent hydrocarbon group, a substituted heterogeneous group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; 
 X is selected from the group consisting of —C, ═C—, a covalent bond, —CH═C═CH—, —CH═CH—, —CH═N—, —C(O)—, —C(O)Y—, —(CH 2 ) n —, wherein n is 2 to 4, —CH 2 NH—, —CH 2 S—, and —CH 2 O—; 
 Y is selected from the group consisting of an oxygen atom, a sulfur atom, and NH; and 
 Z is selected from the group consisting of a carbocyclic group, a heterocyclic group, an aromatic group, a heteroaromatic group, a substituted carbocyclic group, a substituted heterocyclic group, a substituted aromatic group, and a substituted heteroaromatic group; and 
 B) a carrier.