Details for Patent: 7,776,319

Title:	Methods and compositions for treatment of ion imbalances
Abstract:	The present invention provides methods and compositions for the treatment of ion imbalances. In particular, the invention provides compositions comprising sodium-binding polymers and pharmaceutical compositions thereof. Methods of use of the polymeric and pharmaceutical compositions for therapeutic and/or prophylactic benefits are disclosed herein. Examples of these methods include the treatment of hypertension, chronic heart failure, end stage renal disease, liver cirrhosis, chronic renal insufficiency, fluid overload, or sodium overload.
Inventor(s):	Alpern; Robert (Woodbridge, CT), Buysse; Jerry (Los Altos, CA), Chang; Han Ting (Livermore, CA), Charmot; Dominique (Campbell, CA), Cope; Michael James (Berkeley, CA), Fordtran; John (Dallas, TX), Klaerner; Gerrit (San Jose, CA), Connor; Eric (Los Gatos, CA), Liu; Mingjun (Campbell, CA), Liu; Futian (Mountain View, CA), Shao; Jun (Fremont, CA)
Assignee:	Relypsa, Inc. (Santa Clara, CA)
Filing Date:	Mar 30, 2005
Application Number:	11/095,760
Claims:	1. A method of removing sodium from an animal subject comprising administering to an animal subject in need thereof an effective amount of a core-shell composition comprising a cation exchange core and a semi-permeable shell wherein the semi-permeable shell comprises a polymer containing hydrophobic monomers and basic monomers that ionize at low pH and remain neutral beyond their pKa, said hydrophobic monomers selected from the group consisting of a long chain alcohol (meth)acrylate, an N-alkyl (meth)acrylate and an aromatic monomer, and said basic monomers selected from the group consisting of vinyl pyridine and dialkylaminoethyl (meth)acrylamide, wherein the core-shell composition has a high permeability to sodium at low pH and a low permeability to sodium at about neutral pH whereby as the core-shell composition passes through to the lower GI tract, its permeability to sodium decreases. 2. The method of claim 1 wherein said semi-permeable shell has low permeability to sodium ions at neutral pH. 3. The method of claim 1 wherein said cation exchange core comprises a structural unit selected from the group consisting of ##STR00014## 4. The method of claim 1 wherein said semi-permeable shell is essentially not disintegrated during the period of residence and passage through the gastro-intestinal tract. 5. The method of claim 1 wherein said animal subject is suffering from hypertension, chronic heart failure, end stage renal disease, liver cirrhosis, chronic renal insufficiency, fluid overload, or sodium overload. 6. The method of claim 5 wherein extra cellular water is removed from said animal subject. 7. The method of claim 5 wherein a beneficial effect is observed on fluid management, blood pressure control, and/or interdialytic weight gain. 8. The method of claim 1 wherein said animal subject is suffering from a disease characterized by a presence of abnormal quantities of sodium and/or water in the body of said animal subject. 9. The method of claim 1 wherein said animal subject is resistant to diuretic treatment and is suffering from hypertension, chronic heart failure, end stage renal disease, liver cirrhosis, chronic renal insufficiency, fluid overload, or a combination thereof. 10. The method of claim 1 wherein a small amount of sodium is removed from the animal subject over an extended period of time. 11. The method of claim 1 wherein treatment of said animal subject reduces formation of edema after a cardiac event. 12. The method of claim 1 wherein said animal subject is suffering from volume/salt sensitive diastolic heart failure. 13. The method of claim 1 wherein said composition is co-administered with a diuretic, an angiotensin converting enzyme (ACE) inhibitor, an .alpha.-blocker, a .beta.-blocker, an angiotensin II receptor blocker, or a combination thereof. 14. The method of claim 1 wherein said composition is co-administered with a laxative. 15. The method of claim 1, said cation exchange core being capable of binding sodium in an upper gastro-intestinal tract and the semi-permeable shell being characterized by decreased permeability to the bound sodium in a lower gastro-intestinal tract relative to the permeability exhibited to said bound sodium in the upper gastrointestinal tract.