Details for Patent: 7,854,924

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, 2004
Application Number:	10/814,527
Claims:	1. A method of removing sodium from a human subject comprising administering to a human subject in need thereof an effective amount of a non-absorbed sodium-binding composition comprising a sodium-binding polymer, said polymer comprising at least one of polyvinylsulfonate polymer, polyvinylsulfamate polymer, polyvinylsulfamate/vinylsulfate copolymer, vinylphosphonate/acrylic acid copolymer, polyvinylsulfate polymer, or crosslinked polyvinylsulfamate polymer, wherein said human subject is suffering from hypertension, chronic heart failure, end stage renal disease, liver cirrhosis, chronic renal insufficiency, fluid overload, or sodium overload. 2. The method of claim 1 wherein extra cellular water is removed from said human subject. 3. The method of claim 1 wherein said sodium-binding composition exhibits decreased permeability to sodium bound in a lower gastrointestinal tract relative to a permeability exhibited by the sodium-binding composition to said bound sodium in an upper gastrointestinal tract. 4. The method of claim 1 wherein a beneficial effect is observed on fluid management, blood pressure control, and/or interdialytic weight gain. 5. The method of claim 1 wherein said sodium-binding composition swells in an isotonic fluid environment. 6. The method of claim 1 wherein said sodium binding by said sodium-binding composition is dependent on a pH of an environment surrounding said polymeric composition. 7. The method of claim 3 wherein said sodium binding by said sodium-binding composition is dependent on a concentration of bile acids and/or fatty acids in an environment surrounding said polymeric composition. 8. The method of claim 3 wherein said sodium binding by said sodium-binding composition is dependent on an activity of enteric enzymes in an environment surrounding said polymeric composition. 9. The method of claim 1 wherein said human subject is suffering from a disease characterized by a presence of abnormal quantities of sodium and/or water in the body of said human subject. 10. The method of claim 1 wherein said sodium-binding composition does not release Cl.sup.- or OH.sup.-. 11. The method of claim 1 wherein said sodium-binding composition does not release K.sup.+. 12. The method of claim 1 wherein said human subject is resistant to diuretic treatment. 13. The method of claim 1 wherein said sodium-binding polymer comprises repeat units charged with H.sup.+ or NH.sub.4.sup.+ ions. 14. The method of claim 1 wherein said effective amount of sodium-binding composition administered is from about 0.5 grams per day to about 25 grams per day. 15. The method of claim 1 wherein the effective amount of said sodium-binding composition removes about 50 mmol of sodium per day. 16. The method of claim 1 wherein treatment of said human subject reduces the incidence of edema after a cardiac event. 17. The method of claim 1 wherein said human subject is suffering from volume/salt sensitive diastolic heart failure. 18. The method of claim 1 wherein said composition is co-administered with a diuretic, an ACE inhibitor, an .alpha.- blocker, a .beta.- blocker, an angiotensin II receptor blocker, or a combination thereof. 19. The method of claim 1 wherein said composition is co-administered with a laxative. 20. The method of claim 1 wherein said sodium-binding polymer has an in vitro sodium binding capacity of equal to or more than 6 mmol per gram of polymer at a pH of about 7.5. 21. The method of claim 1 wherein the in vivo sodium binding capacity is 4 mmol or more per gram of polymer and is calculated by measuring the amount of sodium in the feces after administration of the sodium-binding polymer to a human patient. 22. The method of claim 21 wherein the in vivo sodium binding capacity is 5 mmol or more per gram of said polymer. 23. The method of claim 21 wherein the in vivo sodium binding capacity is 6 mmol or more per gram of said polymer. 24. The method of claim 21 wherein the in vivo sodium binding capacity is 8 mmol or more per gram of said polymer. 25. The method of claim 1 wherein said sodium binding polymer comprises a crosslinked polymer. 26. The method of claim 1 wherein said human subject is suffering from end stage renal disease. 27. The method of claim 1 wherein said human subject is suffering from chronic heart failure. 28. A method of removing sodium from a human subject comprising administering to a human subject in need thereof an effective amount of a non-absorbed sodium-binding composition comprising a sodium-binding polymer, said polymer comprising at least one of polyvinylsulfonate polymer, polyvinylsulfamate polymer, polyvinylsulfamate/vinylsulfate copolymer, vinylphosphonate/acrylic acid copolymer, polyvinylsulfate polymer, or crosslinked polyvinylsulfamate polymer, wherein said effective amount of sodium-binding composition administered is at least about 5 grams of polymer per day and said human subject is suffering from hypertension, chronic heart failure, end stage renal disease, liver cirrhosis, chronic renal insufficiency, fluid overload, or sodium overload. 29. The method of claim 28 wherein extracellular water is removed from said human subject. 30. The method of claim 28 wherein a beneficial effect is observed on fluid management, blood pressure control, and/or interdialytic weight gain. 31. The method of claim 28 wherein said human subject is suffering from a disease characterized by a presence of abnormal quantities of sodium and/or water in the body of said human subject. 32. The method of claim 28 wherein said human subject is resistant to diuretic treatment. 33. The method of claim 28 wherein treatment of said human subject reduces the incidence of edema after a cardiac event. 34. The method of claim 28 wherein said human subject is suffering from volume/salt sensitive diastolic heart failure. 35. The method of claim 28 wherein said composition is co-administered with a diuretic, an ACE inhibitor, an .alpha.- blocker, a .beta.- blocker, an angiotensin II receptor blocker, or a combination thereof. 36. The method of claim 28 wherein the in vivo sodium binding capacity is 4 mmol or more per gram of polymer and is calculated by measuring the amount of sodium in the feces after administration of the sodium-binding polymer to a human patient. 37. The method of claim 28 wherein said sodium binding polymer comprises a crosslinked polymer. 38. The method of claim 28 wherein said human subject is suffering from end stage renal disease. 39. The method of claim 28 wherein said human subject is suffering from chronic heart failure.