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 - 18 . (canceled) 
     
     
         19 . An oral dosage formulation comprising:
 a Guanylate Cyclase C (GCC) agonist peptide in a per unit dose of 3.0 mg, wherein the GCC agonist peptide consists of an amino acid sequence of SEQ ID NO: 1 as a (4,12; 7,15) bicycle;   an inert low-moisture carrier; and   a lubricant, wherein the GCC agonist peptide has a chromatographic purity of no less than 91% after storage for at least three months.   
     
     
         20 . The oral dosage formulation of  claim 19 , wherein the inert low-moisture carrier is microcrystalline cellulose. 
     
     
         21 . The oral dosage formulation of  claim 20 , wherein the microcrystalline cellulose comprises at least 90% by weight of the formulation. 
     
     
         22 . The oral dosage formulation of  claim 20 , wherein the microcrystalline cellulose comprises at least 95% by weight of the formulation. 
     
     
         23 . The oral dosage formulation of  claim 19 , wherein the lubricant is magnesium stearate. 
     
     
         24 . The oral dosage formulation of  claim 23 , wherein the magnesium stearate comprises about 0.25% by weight of the formulation. 
     
     
         25 . The oral dosage formulation of  claim 19 , wherein the microcrystalline cellulose has a bulk density of 0.28 to 0.34 g/cc. 
     
     
         26 . The oral dosage formulation of  claim 19 , wherein the microcrystalline cellulose has a particle size of 50 to 200 microns. 
     
     
         27 . The oral dosage formulation of  claim 26 , wherein the microcrystalline cellulose has a particle size of 75 to 150 microns. 
     
     
         28 . The oral dosage formulation of  claim 19 , wherein the formulation is in the form of a capsule or tablet. 
     
     
         29 . The oral dosage formulation of  claim 28 , wherein the formulation is in the form of a tablet.