Microencapsulation and sustained release of biologically active polypeptides

Abstract

This invention relates to compositions for the sustained release of biologically active polypeptides, and methods of forming and using said compositions, for the sustained release of biologically active polypeptides. The sustained release compositions of this invention comprise a biocompatible polymer having dispersed therein, a biologically active polypeptide, a sugar and a salting-out salt.

1 . A method for reducing body weight comprising administering to a subject in need of, or desirous of weight reduction, a formulation comprising an amount of at least one compound selected from the group consisting of an exendin, an exendin agonist, or an exendin agonist analog in a manner sufficient to maintain a daily average plasma concentration of said exendin, exendin agonist or exendin analog agonist of at least 100 pg/ml over a period of at least 12 hours.  
   
   
       2 . The method of  claim 1 , wherein said daily average plasma concentration is between about 100 pg/ml and about 600 pg/ml.  
   
   
       3 . The method of  claim 2 , wherein said daily average plasma concentration is between about 170 pg/ml and about 350 pg/ml.  
   
   
       4 . The method of  claim 2 , wherein the said daily average plasma concentration is maintained over a period of at least one week.  
   
   
       5 . The method of  claim 1 , wherein said compound is exendin-4.  
   
   
       6 . The method of  claim 5  further comprises a biocompatible polymer.  
   
   
       7 . The method of  claim 6  further comprises a sugar.  
   
   
       8 . The method of  claim 1 , wherein said formulation is administered intravenously, transmucosally, intranasally, orally, intramuscularly, transdermally, by inhalation, or by pulmonary administration.  
   
   
       9 . A method for reducing body weight comprising administering to a subject in need of, or desirous of weight reduction, a formulation comprising an amount of at least one compound selected from the group consisting of an exendin, an exendin agonist, or an exendin agonist analog in a manner sufficient to maintain a minimum plasma concentration of said exendin, exendin agonist or exendin analog agonist of at least 50 pg/ml over a period of at least 12 hours.  
   
   
       10 . The method of  claim 9 , wherein said minimum plasma concentration is between about 100 pg/ml and about 600 pg/ml.  
   
   
       11 . The method of  claim 9 , wherein said minimum plasma concentration is between about 170 pg/ml and about 350 pg/ml.  
   
   
       12 . The method of  claim 11 , wherein the said daily average plasma concentration is maintained over a period of at least one week.  
   
   
       13 . The method of  claim 9 , wherein said compound is exendin-4.  
   
   
       14 . The method of  claim 13  further comprises a biocompatible polymer.  
   
   
       15 . The method of  claim 14  further comprises a sugar.  
   
   
       16 . The method of  claim 9 , wherein said formulation is administered intravenously, transmucosally, intranasally, orally, intramuscularly, transdermally, by inhalation, or by pulmonary administration.  
   
   
       17 . A method for treating diabetes, comprising administering to a subject in need of, or desirous of weight reduction, a formulation comprising an amount of at least one compound selected from the group consisting of an exendin, an exendin agonist, or an exendin agonist analog in a manner sufficient to maintain a minimum plasma concentration of said exendin, exendin agonist or exendin analog agonist of at least 50 pg/ml over a period of at least 12 hours.  
   
   
       18 . The method of  claim 17 , wherein said minimum plasma concentration is between about 100 pg/ml and about 600 pg/ml.  
   
   
       19 . The method of  claim 17 , wherein said minimum plasma concentration is between about 170 pg/ml and about 350 pg/ml.  
   
   
       20 . The method of  claim 18 , wherein the said minimum plasma concentration is maintained over a period of at least one week.  
   
   
       21 . The method of  claim 17 , wherein said compound is exendin-4.  
   
   
       22 . The method of  claim 21  further comprises a biocompatible polymer.  
   
   
       23 . The method of  claim 22  further comprises a sugar.  
   
   
       24 . The method of  claim 17 , wherein said formulation is administered intravenously, transmucosally, intranasally, orally, intramuscularly, transdermally, by inhalation, or by pulmonary administration.  
   
   
       25 . The method of  claim 17 , wherein said diabetes is Type I or Type II.