Formulations of guanylate cyclase c agonists and methods of use

Abstract

The invention provides novel formulations of guanylate cyclase-C (“GCC”) agonist peptides and methods for their use in the treatment of gastrointestinal diseases and disorders, including gastrointestinal cancer. The GCC agonist formulations of the invention can be administered either alone or in combination with one or more additional therapeutic agents, preferably an inhibitor of cGMP-dependent phosphodiesterase or a laxative.

1 - 24 . (canceled) 
     
     
         25 . A method for treating constipation in a subject in need thereof, comprising administering to the subject a GCC agonist formulation comprising (1) a core, which contains at least one GCC agonist peptide, and (2) pH-dependent polymer which degrades in a pH range of 4.5 to 5.5 or in a pH range of 5.5 to 6.5, wherein the formulation is optimized for delivery of the GCC agonist peptide to the duodenum or jejunum, wherein the GCC agonist peptide is selected from the group consisting of SEQ ID NOs: 1-44 and 99-107, and wherein upon administration to a subject in need thereof, said formulation results in fewer unwanted side effects compared to a formulation not optimized for delivery the duodenum or jejunum. 
     
     
         26 - 33 . (canceled) 
     
     
         34 . The method of  claim 25 , further comprising administering to the subject an effective amount of an inhibitor of a cGMP-specific phosphodiesterase. 
     
     
         35 . (canceled) 
     
     
         36 . The method of  25 , further comprising administering to the subject an effective amount of at least one laxative. 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 25 , further comprising administering to the subject an effective amount of at least one anti-inflammatory agent. 
     
     
         39 . The method of  claim 25 , wherein the subject is a human.