Pharmaceutical Formulation for Regulating the Timed Release of Biologically Active Compounds Based on a Polymer Matrix

Abstract

A formulation containing a biologically active compound having a structure with hydrogen bonding sites is blended with a polymer having a structure with complementary hydrogen bonding sites, the polymer forming hydrolytic degradation products that promote the release of the biologically active compound from the polymer.

1 . An implant comprising:
 a weight percentage of a peptide drug having a chemical structure with hydrogen bonding sites; and   a hydrolytically degradable polycarbonate copolymer having a molar percentage of tyrosine-derived diphenol monomer units with pendant carboxylic acid groups and a molar percentage of tyrosine-derived diphenol monomer units with pendant carboxylic acid ester groups,   
       wherein the peptide drug is dispersed within the copolymer. 
     
     
         2 . The implant of  claim 1  wherein the polycarbonate copolymer degrades hydrolytically promoting release of the peptide drug from the implant. 
     
     
         3 . The implant of  claim 1  wherein the molar percentage of tyrosine-derived diphenol monomer units with pendant carboxylic acid groups is between about 5 mole percent and about 15 mole percent. 
     
     
         4 . The implant of  claim 1  wherein the weight percentage of the peptide drug is between about 15 weight percent and about 30 weight percent. 
     
     
         5 . The implant of  claim 1  wherein the molar percentage of tyrosine-derived diphenol monomer units with pendant carboxylic acid groups and the weight percentage of the peptide drug is effective to provide reproducible release profiles of the peptide drug from the implant without an initial burst effect. 
     
     
         6 . The implant of  claim 1  wherein the copolymer is a desaminotyrosyltyrosine copolymer of poly(desaminotyrosyltyrosine ethyl ester carbonate). 
     
     
         7 . The implant of  claim 1  wherein the peptide drug is a cyclic peptide. 
     
     
         8 . A formulation comprising:
 a weight percentage of a biologically active compound having a chemical structure with hydrogen bonding sites; and   a hydrolytically degradable polycarbonate copolymer having a molar percentage of tyrosine-derived diphenol monomer units with pendant carboxylic acid groups and a molar percentage of tyrosine-derived diphenol monomer units with pendant carboxylic acid ester groups,   
       wherein the polycarbonate copolymer degrades hydrolytically promoting release of the biologically active compound from the formulation. 
     
     
         9 . The formulation of  claim 8  wherein the molar percentage of tyrosine-derived diphenol monomer units with pendant carboxylic acid groups and the weight percentage of the biologically active compound is effective to provide reproducible release profiles of the biologically active compound from the formulation without an initial burst effect. 
     
     
         10 . The formulation of  claim 8  wherein the biologically active compound is a pharmaceutically active compound. 
     
     
         11 . The formulation of  claim 10  wherein the pharmaceutically active compound is a peptide. 
     
     
         12 . The formulation of  claim 11  wherein the peptide is a cyclic peptide. 
     
     
         13 . The formulation of  claim 8  wherein the copolymer is a desaminotyrosyltyrosine copolymer of poly(desaminotyrosyltyrosine ethyl ester carbonate). 
     
     
         14 . The formulation of  claim 8  wherein the molar percentage of tyrosine-derived diphenol monomer units with pendant carboxylic acid groups is between about 5 mole percent and about 15 mole percent. 
     
     
         15 . The formulation of  claim 8  wherein the weight percentage of biologically active compound is between about 15 weight percent and about 30 weight percent. 
     
     
         16 . A method for delayed delivery of a peptide drug to a patient in need thereof comprising:
 providing a formulation including the peptide drug and a copolymer,
 wherein the peptide drug has a chemical structure with hydrogen bonding sites, and 
 wherein the copolymer is a hydrolytically degradable polycarbonate copolymer having tyrosine-derived diphenol monomer units with pendant carboxylic acid groups and tyrosine-derived diphenol monomer units with pendant carboxylic acid ester groups; and 
   administering the formulation to the patient so that release of the peptide drug occurs after a predetermined time without an initial burst effect.   
     
     
         17 . The method of  claim 16  wherein a weight percentage of the peptide drug in the formulation is between about 15 weight percent and about 30 weight percent. 
     
     
         18 . The method of  claim 16  wherein a molar percentage of tyrosine-derived diphenol monomer units with pendant carboxylic acid groups is between about 5 mole percent and about 15 mole percent. 
     
     
         19 . The method of  claim 16  wherein the peptide drug is a cyclic peptide. 
     
     
         20 . The method of  claim 16  wherein the copolymer is a desaminotyrosyltyrosine copolymer of poly(desaminotyrosyltyrosine ethyl ester carbonate).