Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders

Abstract

The invention provides novel guanylate cyclase-C agonist peptides and their use in the treatment of human diseases including gastrointestinal disorders, inflammation or cancer (e.g., a gastrointestinal cancer). The peptides can be administered either alone or in combination with an inhibitor of cGMP-dependent phosphodiesterase. The gastrointestinal disorder may be classified as either irritable bowel syndrome, constipation, or excessive acidity etc. The gastrointestinal disease may be classified as either inflammatory bowel disease or other GI condition, including Crohn's disease and ulcerative colitis, and cancer.

We claim: 
     
         1 . A method for preventing, treating, or alleviating a symptom of irritable bowel syndrome comprising rectally administering to a subject in need thereof a therapeutically effective amount of a composition comprising the peptide of SEQ ID NO: 9, wherein said peptide is a (4,12:7,15) bicycle. 
     
     
         2 . The method of  claim 1 , wherein the effective amount is between about 1 mg to 10 mg per dose. 
     
     
         3 . The method of  claim 2 , wherein the composition is administered once daily. 
     
     
         4 . The method of  claim 1 , wherein the composition is an enema. 
     
     
         5 . The method of  claim 1 , wherein the composition is a suppository. 
     
     
         6 . The method of  claim 1 , wherein the release of the composition is delayed. 
     
     
         7 . A formulation for rectal administration comprising the peptide of SEQ ID NO: 9, wherein said peptide is a (4,12:7,15) bicycle. 
     
     
         8 . The formulation of  claim 7 , wherein the formulation is a liquid. 
     
     
         9 . The formulation of  claim 8 , wherein the liquid is saline. 
     
     
         10 . The formulation of  claim 7 , wherein the formulation is an enema. 
     
     
         11 . The formulation of  claim 7 , wherein the formulation is a suppository.