Formulations of guanylate cyclase c agonists and methods of use

Abstract

The invention provides low-dose formulations of guanylate cyclase-C (“GCC”) agonist peptides and methods for their use. The 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 - 20 . (canceled) 
     
     
         21 . A method for treating or preventing a disease or disorder in a subject in need thereof comprising administering to the subject an oral dosage formulation comprising at least one GCC agonist peptide and one or more pharmaceutically acceptable excipients,
 wherein the amount of GCC agonist peptide per unit dose is from 0.01 mg to 10 mg,   wherein the GCC agonist peptide is selected from the group consisting of SEQ ID Nos: 1-54 and 56-249,   wherein the GCC agonist peptide has a chromatographic purity of no less than 91%, and   wherein the disease or disorder is a gastrointestinal disease or disorder selected from the group consisting of non-ulcer dyspepsia, chronic intestinal pseudo-obstruction, functional dyspepsia, colonic pseudo-obstruction, duodenogastric reflux, gastro esophageal reflux disease, gastroparesis, heartburn, gastric cancer, and  H. pylori  infection.   
     
     
         22 . The method of  claim 21 , wherein the GCC agonist peptide is selected from the group consisting of SEQ ID NOs: 1, 8, 9, and 56. 
     
     
         23 . The method of  claim 22 , wherein the GCC agonist peptide is SEQ ID NO: 1 or SEQ ID NO: 9. 
     
     
         24 . The method of  claim 21 , further comprising administering to the subject an effective amount of an inhibitor of a cGMP-specific phosphodiesterase. 
     
     
         25 . The method of  claim 21 , further comprising administering to the subject an effective amount of at least one laxative. 
     
     
         26 . The method of  claim 21 , further comprising administering to the subject an effective amount of at least one anti-inflammatory agent. 
     
     
         27 . The method of  claim 21 , wherein the GCC agonist peptide is stabilized against degradation for a period of at least 18 months at 30° C. and 65% relative humidity, or at least 18 months at 25° C. and 60% relative humidity, or at least 18 months at 2-8° C. 
     
     
         28 . The method of  claim 21 , wherein the formulation contains less than 0.2% by weight of each of inorganic acids and carboxylic acids.