Pharmaceutical compositions for treating hyperkalemia

Patent metadata

Field	Value
Publication number	US-9545425-B2
Application number	US-201615052190-A
Country	US
Kind code	B2
Filing date	Feb 24, 2016
Priority date	Dec 23, 2014
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

The present invention is directed to compositions and methods of removing potassium or treating hyperkalemia by administering pharmaceutical compositions of cation exchange polymers with low crosslinking for improved potassium excretion and for beneficial physical properties to increase patient compliance.

First claim

What is claimed is:

1. A pharmaceutical composition comprising:
i) about 89% to about 94.5% of a calcium salt of a crosslinked potassium binding polymer having the following structure:

wherein the ratio of “m” and “n” provides having 1.6% to 1.9% cross-linking;
ii) about 0.6% to about 1.6% of calcium citrate tetrahydrate;
iii) about 0.02% to about 0.5% of anhydrous citric acid;
iv) about 0.1% to about 1% of sucralose;
v) about 0.6% to about 1.6% of vanillin powder;
vi) about 2.5% to about 3.5% of methyl cellulose; and
vii) about 1.6% to about 2.6% of titanium dioxide.

2. The pharmaceutical composition of claim 1 , wherein the ratio of m to n is 68:1.

3. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer is characterized by a swelling ratio in water of between about 3 grams of water per gram of polymer to about 8 grams of water per gram of polymer.

4. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer is characterized by a swelling ratio in water of between about 3 grams of water per gram of polymer to about 4.5 grams of water per gram of polymer.

5. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer is characterized by a swelling ratio in water of about 3.3 grams of water per gram of polymer.

6. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer is characterized by a swelling ratio in water of about 4.3 grams of water per gram of polymer.

7. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer further comprises substantially spherical particles having a median diameter from about 5 μm to about 130 μm.

8. The pharmaceutical composition of claim 7 , wherein the particles have an average particle size Dv(0.9) between about 80 μm to about 130 μm.

9. The pharmaceutical composition of claim 8 , wherein the particles have an average particle size Dv(0.9) between about 90 μm to about 120 μm.

10. The pharmaceutical composition of claim 7 , wherein the particles have an average particle size Dv(0.9) between about 40 μm to about 70 μm.

11. The pharmaceutical composition of claim 10 , wherein the particles have an average particle size Dv(0.9) between about 50 μm to about 60 μm.

12. The pharmaceutical composition of claim 7 , wherein the particles have an average particle size Dv(0.5) between about 60 μm to about 90 μm.

13. The pharmaceutical composition of claim 12 , wherein the particles have an average particle size Dv(0.5) between about 70 μm to about 80 μm.

14. The pharmaceutical composition of claim 7 , wherein the particles have an average particle size Dv(0.5) between about 20 μm to about 50 μm.

15. The pharmaceutical composition of claim 14 , wherein the particles have an average particle size Dv(0.5) between about 30 μm to about 40 μm.

16. The pharmaceutical composition of claim 7 , wherein the particles have an average particle size Dv(0.1) between about 20 μm to about 70 μm.

17. The pharmaceutical composition of claim 16 , wherein the particles have an average particle size Dv(0.1) between about 30 μm to about 60 μm.

18. The pharmaceutical composition of claim 7 , wherein the particles have an average particle size Dv(0.1) between about 5 μm to about 30 μm.

19. The pharmaceutical composition of claim 18 , wherein the particles have an average particle size Dv(0.1) between about 6 μm to about 23 μm.

20. The pharmaceutical composition of claim 1 , wherein ratio of Dv(0.9):Dv(0.5) is about two or less and the ratio of Dv(0.5):Dv(0.1) is about five or less.

21. The pharmaceutical composition of claim 1 , wherein the ratio of Dv(0.9):Dv(0.5) and the ratio of Dv(0.5):Dv(0.1) are each independently about two or less.

22. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer has a potassium exchange capacity from about 1 mEq to about 4 mEq per gram of potassium binding polymer.

23. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer has a Mouth Feel score greater than 3.5.

24. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer has a Mouth Feel score greater than 4.5.

25. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer has a Mouth Feel score greater than 5.0.

26. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer is characterized by a crosslinking of about 1.8%, wherein the term about means ±5%.

27. The pharmaceutical composition of claim 1 , wherein the potassium binding polymer is characterized by a crosslinking of 1.8%.

28. A pharmaceutical composition comprising:
i) about 89% to about 94.5% of a calcium salt of a crosslinked potassium binding polystyrene sulfonate divinylbenzene polymer characterized by a crosslinking of 1.6%to 1.9%;
ii) about 0.6% to about 1.6% of calcium citrate tetrahydrate;
iii) about 0.02% to about 0.5% of anhydrous citric acid;
iv) about 0.1% to about 1% of sucralose;
v) about 0.6% to about 1.6% of vanillin powder;
vi) about 2.5to about 3.5% of methyl cellulose; and
vii) about 1.6% to about 2.6% of titanium dioxide.

Assignees

• Ardelyx Inc

Inventors

• Charmot Dominique
• Davidson James P
• Lin Fangling
• Jacobs Jeffrey W
• Blinova Natalia
• Labonte Eric
• Langsetmo Ingrid
• Blanks Robert C

Classifications

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title

• A61K9/0095

  Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006) · CPC title

• A61K31/795 Primary

  Polymers containing sulfur · CPC title

• B01J39/20

  obtained by reactions only involving unsaturated carbon-to-carbon bonds · CPC title

• A61K9/10

  Dispersions; Emulsions · CPC title