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Details for Patent: 8,445,014

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Details for Patent: 8,445,014

Title:Ion binding compositions
Abstract: The present invention provides methods and compositions for the treatment of ion imbalances. In particular, the invention provides core-shell compositions and pharmaceutical compositions thereof. Methods of use of the core-shell compositions for therapeutic and/or prophylactic benefits are disclosed herein. Examples of these methods include the treatment of phosphate imbalance disorders, hypertension, chronic heart failure, end stage renal disease, liver cirrhosis, chronic renal insufficiency, fluid overload, or sodium overload.
Inventor(s): Charmot; Dominique (Campbell, CA), Chang; Han-Ting (Livermore, CA), Connor; Eric (Los Gatos, CA), Liu; Mingjun (Campbell, CA), Klaerner; Gerrit (San Jose, CA)
Assignee: Relypsa, Inc. (Redwood City, CA)
Filing Date:Sep 26, 2008
Application Number:12/238,844
Claims:1. A method for removing potassium from an animal subject in need thereof comprising administering core-shell particles comprising a core component encapsulated in a shell component to the animal subject, said core component comprising a potassium binding polymer, said shell component comprising a crosslinked amine functional polymer alkylated with hydrophobic agent(s).

2. The method of claim 1 wherein said core-shell particles have a capacity for binding potassium ion in a gastrointestinal tract of said animal subject.

3. The method of claim 2 wherein said core-shell particles retain a significant amount of said bound potassium ion during a period of residence of the core-shell particles in the gastrointestinal tract of said animal subject.

4. The method of claim 1 wherein the core component comprises crosslinked carboxylate, phosphonate, sulfate, sulfonate, sulfamate polymers or combinations thereof.

5. The method of claim 1 wherein the alkylating agents have the formula RX where R is a C.sub.1-C.sub.20 alkyl, C.sub.1-C.sub.20 hydroxy-alkyl, C.sub.6-C.sub.20 aralkyl, C.sub.1-C.sub.20 alkylammonium, or C.sub.1-C.sub.20 alkylamido group and X comprises one or more electrophilic groups.

6. The method of claim 1 wherein the alkylating agent is an alkyl or alkylaryl group carrying an amine-reactive electrophile.

7. The method of claim 1 wherein the alkylating agent is selected from the group consisting of benzyl halide and dodecyl halide.

8. The method of claim 1 wherein the alkylating agent includes at least two electrophilic groups X.

9. The method of claim 8 wherein the alkylating agent is selected from the group consisting of di-haloalkane, dihalopolyethylene glycol, and epichlorohydrin.

10. The method of claim 1 wherein the shell thickness is from about 0.002 .mu.m to about 50 .mu.m.

11. The method of claim 1 wherein the shell to core weight ratio is 0.01% to 50%.

12. The method of claim 1 wherein the size of the core-shell particle is from about 200 nm to about 2 mm.

13. The method of claim 1 wherein the animal subject suffers from hyperkalemia, depressed renal synthesis of calcitriol, renal insufficiency, hypertension, chronic heart failure, end stage renal disease, fluid overload, or anabolic metabolism.

14. The method of claim 1 wherein the animal subject patient suffers from hyperkalemia.

15. A method of removing potassium from a patient in need thereof comprising administering core-shell particles to the patient, said core-shell particles comprising a core component encapsulated in a shell component, said core component comprising a crosslinked potassium binding polymer, said shell component comprising a crosslinked amine functional polymer alkylated with an alkyl or alkylaryl group.

16. The method of claim 15, the core component comprising crosslinked carboxylate, phosphonate, sulfate, sulfonate, sulfamate polymers or combinations thereof.

17. The method of claim 15 wherein the shell thickness is from about 0.002 .mu.m to about 50 .mu.m.

18. The method of claim 15 wherein the alkylating agent is a benzyl halide.

19. The method of claim 15 wherein the size of the core-shell particle is from about 200 nm to about 2 mm.

20. The method of claim 19 wherein the alkylating agent is a benzyl halide.

21. The method of claim 15 wherein the patient suffers from hyperkalemia, depressed renal synthesis of calcitriol, renal insufficiency, hypertension, chronic heart failure, end stage renal disease, fluid overload, or anabolic metabolism.

22. The method of claim 15 wherein the patient suffers from hyperkalemia.
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