Agonists of guanylate cyclase and their uses
View Patent ↗This invention provides a method of colonic cleansing.
1. A method of colonic cleansing, comprising administering to a subject in need thereof a unit dose of 0.01 mg to 60 mg of a guanylate cyclase receptor agonist (GCRA) peptide consisting essentially of the sequence of SEQ ID NO: 9.
2. The method of claim 1 , wherein said peptide is bicyclic consisting essentially of the sequence of SEQ ID NO: 9.
3. The method of claim 1 , further comprising administering to said subject an effective amount of an osmotic colonic evacuant.
4. The method of claim 3 , wherein said osmotic colonic evacuant is magnesium citrate.
5. The method of claim 3 , wherein said osmotic colonic evacuant is a phosphate salt laxative.
6. The method of claim 1 , further comprising administering to said subject an effective amount of L-glucose, lubiprostone (Amitiza), prucalopride, an agent for treating chronic constipation, or any combination thereof.
7. The method of claim 6 , wherein said effective amount of L-glucose is a unit dose of 20 g-200 g.
8. The method of claim 1 , further comprising administering to said subject an effective amount of a cGMP-specific phosphodiesterase inhibitor.
9. The method of claim 8 , wherein said cGMP-specific phosphodiesterase inhibitor is selected from the group consisting of sulindac sulfone, zaprinast, motapizone, vardenafil, and sildenafil.
10. A formulation comprising a mixture of:
a. a composition comprising an inert carrier coated with GCRA peptides consisting essentially of the sequence of SEQ ID NO: 9 wherein said composition comprising an enteric coating that releases the peptides at pH5.0; and
b. a composition comprising an inert carrier coated with GCRA peptides consisting essentially of the sequence of SEQ ID NO: 9 wherein said composition comprising an enteric coating that releases the peptides at pH6.0 or pH 7.0.
11. The formulation of claim 10 , wherein the inert carrier is a selected from mannitol, lactose, a microcrystalline cellulose, or starch.
12. The formulation of claim 10 , wherein the amount of GCRA peptide per unit dose is from 1 mg to 60 mg.
13. A method of colonic cleansing, comprising administering to a subject in need thereof the formulation of claim 10 .