Compositions and methods for treating precocious puberty

Abstract

The present invention is directed to the controlled delivery of gonadotropin-releasing hormone (GnRH) agonists, preferably from a polymeric material that is implanted in the body. More specifically, the present invention relates to compositions comprised of a GnRH agonist, preferably histrelin, in a polymeric material that results in a desired and controlled delivery of a therapeutically effective amount of GnRH agonist over an extended period of time in order to treat central precocious puberty (CPP).

1 . A controlled release reservoir implant containing a formulation comprising histrelin or its pharmaceutically acceptable salt, the reservoir implant comprising a hydrophilic copolymer obtained from a copolymerization of a mixture comprising at least two hydrophilic, ethylenically unsaturated monomers, and which implant upon implantation in a patient suffering from central precocious puberty provides an average in vivo release rate between 60 micrograms and 70 micrograms of the histrelin or its salt daily in the patient. 
     
     
         2 . The implant of  claim 1  in which the at least two monomers comprise 2-hydroxyethyl methacrylate (HEMA) and hydroxypropyl methacrylate (HPMA). 
     
     
         3 . The implant of  claim 1  in which the mixture comprises about 45% of HEMA and about 55% HPMA. 
     
     
         4 . The implant of  claim 1  in which the mixture comprises about 45% of HEMA, about 54.5% HPMA and about 0.5% trimethylolpropane trimethacrylate (TMPTMA). 
     
     
         5 . The implant of  claim 1  which provides an average in vitro release rate of about 65 micrograms of the histrelin or its salt per day. 
     
     
         6 . The implant of  claim 1  which releases histrelin or its salt at a rate to maintain a mean plasma concentration of histrelin of about 0.2 ng/ml to about 2 ng/ml over at least two months. 
     
     
         7 . The implant of  claim 1  which releases histrelin or its salt at a rate to maintain a mean plasma concentration of histrelin of about 0.4 ng/ml to about 0.6 ng/ml over at least two months. 
     
     
         8 . A controlled release reservoir implant containing a formulation comprising histrelin or its pharmaceutically acceptable salt, the reservoir implant comprising a hydrophilic copolymer obtained from a copolymerization of a mixture comprising at least two hydrophilic, ethylenically unsaturated monomers, and which implant upon implantation in a patient suffering from central precocious puberty provides an average in vivo release rate between 60 micrograms and 70 micrograms of the histrelin or its salt daily in the patient to maintain a mean plasma concentration of histrelin of about 0.2 ng/ml to about 2 ng/ml over at least six months. 
     
     
         9 . The implant of  claim 8  in which the histrelin or its salt is released at a rate to maintain a mean plasma concentration of histrelin of about 0.4 ng/ml to about 0.6 ng/ml over at least six months. 
     
     
         10 . A controlled release reservoir implant containing a formulation comprising 50 mg histrelin acetate, the reservoir implant comprising a hydrophilic copolymer obtained from a copolymerization of a mixture comprising about 45% HEMA, 54.5% HPMA and about 0.5% TMPTMA, and which implant provides an average in vitro release rate of about 65 micrograms of the histrelin acetate daily. 
     
     
         11 . The implant of  claim 10  which upon implantation in a patient suffering from central precocious puberty releases histrelin acetate daily in the patient at a rate to maintain a mean plasma concentration of histrelin of about 0.2 ng/ml to about 2 ng/ml over at least six months. 
     
     
         12 . The implant of  claim 11  in which the mean plasma concentration of histrelin is maintained over a period of about twelve months.