Compositions And Methods For Stimulating Hair Growth

Abstract

Methods and compositions for stimulating the growth of hair are disclosed wherein said compositions include a cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula (I) wherein the dashed bonds represent the presence or absence of a double bond which can be in the cis or trans configuration and A, B, Z, X, R 1 and R 2 are as defined in the specification and a penetration enhancer. Such compositions are used in stimulating hair growth of human or non-human animals.

1 . A composition for growing hair by topical application comprising:
 at least one penetration enhancer; and   0.01% to 0.3% w/w cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I:   
       
         
           
           
               
               
           
         
         wherein the dashed bonds represent the presence or absence of a double bond which can be in the cis or trans configuration, A is an alkylene or alkenylene radical having from two to six carbon atoms, which radical can be interrupted by one or more oxa radicals and substituted with one or more hydroxy, oxo, alkyloxy or alkylcarboxy groups wherein the alkyl radical comprises from one to six carbon atoms; B is a cycloalkyl radical having from three to seven carbon atoms, or an aryl radical, selected from the group consisting of hydrogen, a lower alkyl radical having from four to ten carbon atoms wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms; X is —N(R 4 ) 2  wherein R 4  is selected from the group consisting of hydrogen, a lower alkyl radical having from one to six carbon atoms, 
       
       
         
           
           
               
               
           
         
         wherein R 5  is a lower alkyl radical having from one to six carbon atoms; Z is ═O; one of R 1  and R 2  is ═O, —OH or a—O(CO)R 6  group, and the other one is —OH or —O(CO)R 6 , or R 1  is ═O and R 2  is H, wherein R 6  is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or —(CH 2 )mR 7  wherein m is 0 or an integer of from 1 to 10, and R 7  is cycloalkyl radical, having from three to seven carbon atoms, or a hydrocarbyl aryl or heteroaryl radical, as defined above in free form or a pharmaceutically acceptable salt thereof, in association with a penetration enhancer in particular formulations adapted for topical application to mammalian skin; 
         wherein said composition is formulated for topical administration to the skin. 
       
     
     
         2 . The composition according to  claim 1  wherein said cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I is bimatoprost. 
     
     
         3 . The composition according to  claim 1  wherein the penetrating enhancer is selected from the group consisting of propylene glycol, diethylene glycol monoether, ethyl alcohol and glycerin. 
     
     
         4 . The composition according to  claim 1  wherein the penetrating enhancer is selected from the group consisting of at least two compounds selected from the group consisting of propylene glycol, diethylene glycol monoether, ethyl alcohol and glycerin. 
     
     
         5 . A composition according to  claim 1  wherein the penetrating enhancer consists of the following compounds: propylene glycol, diethylene glycol monoether, ethyl alcohol and glycerin. 
     
     
         6 . A composition according to  claim 1  comprising from 0.03-0.3% w/w bimatoprost, about 10% w/w propylene glycol, about 10% w/w diethylene glycol monoether, about 30% w/w ethyl alcohol, about 2% w/w glycerin, about 0.15% w/w carbomer, about 0.16% w/w triethanolamine, and purified water. 
     
     
         7 . The composition according to  claim 6  comprising 0.03% w/w bimatoprost. 
     
     
         8 . The composition of  claim 6  wherein the composition comprises 0.1% w/w bimatoprost. 
     
     
         9 . The composition of  claim 6  wherein the composition comprises 0.2% bimatoprost. 
     
     
         10 . The composition of  claim 6  wherein the composition consists of 0.3% w/w bimatoprost. 
     
     
         11 . The composition according to  claim 6  wherein the composition is in the form of one selected from the group consisting of solutions, gels, ointments, foams, films, liniments, creams, shampoos, lotions, pastes, jellies, sprays and aerosols. 
     
     
         12 . The composition of  claim 11  wherein the composition is packaged in a kit with an applicator for application to the skin. 
     
     
         13 . A method for stimulating hair growth comprising topically administering a composition comprising:
 at least one penetration enhancer; and   a cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I:   
       
         
           
           
               
               
           
         
         wherein the dashed bonds represent the presence or absence of a double bond which can be in the cis or trans configuration, A is an alkylene or alkenylene radical having from two to six carbon atoms, which radical can be interrupted by one or more oxa radicals and substituted with one or more hydroxy, oxo, alkyloxy or alkylcarboxy groups wherein the alkyl radical comprises from one to six carbon atoms; B is a cycloalkyl radical having from three to seven carbon atoms, or an aryl radical, selected from the group consisting of hydrogen, a lower alkyl radical having from four to ten carbon atoms wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms; X is —N(R 4 ) 2  wherein R 4  is selected from the group consisting of hydrogen, a lower alkyl radical having from one to six carbon atoms, 
       
       
         
           
           
               
               
           
         
         wherein R 5  is a lower alkyl radical having from one to six carbon atoms; Z is ═O; one of R 1  and R 2  is ═O, —OH or a—O(CO)R 6  group, and the other one is —OH or —O(CO)R 6 , or R 1  is ═O and R 2  is H, wherein R 6  is a saturated or unsaturated acyclic hydrocarbon group having from 1 to about 20 carbon atoms, or —(CH 2 )mR 7  wherein m is 0 or an integer of from 1 to 10, and R 7  is cycloalkyl radical, having from three to seven carbon atoms, or a hydrocarbyl aryl or heteroaryl radical, as defined above in free form or a pharmaceutically acceptable salt thereof, in association with a penetration enhancer in particular formulations adapted for topical application to mammalian skin; 
         wherein said composition is formulated for topical administration to the skin. 
       
     
     
         14 . The method according to  claim 13  wherein said cyclopentane heptanoic acid, 2-cycloalkyl or arylalkyl compound represented by the formula I is bimatoprost. 
     
     
         15 . The method according to  claim 14  comprising bimatoprost at a concentration of about 0.03% w/w to about 0.3% w/w. 
     
     
         16 . The method according to  claim 14  comprising bimatoprost at about 0.1% w/w; about 10% w/w propylene glycol, about 10% w/w diethylene glycol monoether, about 30% w/w ethyl alcohol, about 2% w/w glycerin, about 0.15% w/w carbomer, about 0.16% w/w triethanolamine, and purified water. 
     
     
         17 . The method according to according to  claim 14  comprising bimatoprost at about 0.3% w/w; about 10% w/w propylene glycol, about 10% w/w diethylene glycol monoether, about 30% w/w ethyl alcohol, about 2% w/w glycerin, about 0.15% w/w carbomer, about 0.16% w/w triethanolamine, and purified water. 
     
     
         18 . The method according to  claim 14 , wherein the composition is applied at least once daily to the scalp. 
     
     
         19 . The method according to  claim 14 , wherein the composition is applied at least once daily to the scalp for treatment of one of the following conditions selected from the group consisting of alopecia greata, telogen effluvium, anagen effluvium, cicatricial alopecia, scarring alopecia; hair shaft abnormalities, trichorrexis nodosa, loose anagen syndrome, trichotillomania, traction alopecia; infectious hair disorders, tiniea capitis, sebohorreic dermatitis, follicullitus of the scalp, and androgenetic alopecia. 
     
     
         20 . The method according to  claim 14  wherein the composition is applied at least once a day to both the scalp and the eyebrows for patients experiencing hair loss due to chemotherapy, hormonal imbalance, fungal infection of the scalp, anti-coagulants, medicine for gout, depression, high blood pressure and heart disease.