Compositions and methods for treating hyperkalemia

Patent metadata

Field	Value
Publication number	US-2016346318-A1
Application number	US-201514912682-A
Country	US
Kind code	A1
Filing date	Dec 22, 2015
Priority date	Dec 23, 2014
Publication date	Dec 1, 2016
Grant date	—

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 calcium salt of a crosslinked potassium binding polymer having the structure of Formula (I):

or a pharmaceutically acceptable salt thereof,
wherein:
each R 1 is independently selected from the group consisting of H, substituted or unsubstituted (C 1 -C 6 )alkyl, substituted or unsubstituted (C 6 -C 18 )aryl, —S(O) 2 OH, —OS(O) 2 OH, —C(O)OH, —PO(OH) 2 , —OP(OH) 3 , and —NHS(O) 2 OH;
each R 2 is independently selected from the group consisting of H, substituted or unsubstituted (C 1 -C 6 )alkyl, substituted or unsubstituted (C 6 -C 18 )aryl, —S(O) 2 OH, —OS(O) 2 OH, —C(O)OH, —PO(OH) 2 , —OP(OH) 3 , and —NHS(O) 2 OH;
each R 3 is independently selected from the group consisting of H, halogen, substituted or unsubstituted (C 1 -C 6 )alkyl, substituted or unsubstituted (C 6 -C 18 )aryl, —S(O) 2 OH, —OS(O) 2 OH, —C(O)OH, —PO(OH) 2 , —OP(OH) 3 , and —NHS(O) 2 OH;
each X is either absent or independently selected from the group consisting of substituted or unsubstituted (C 1 -C 6 )alkyl and substituted or unsubstituted (C 6 -C 18 )aryl,
each Y is independently selected from the group consisting of substituted or unsubstituted (C 1 -C 6 )alkyl and substituted or unsubstituted (C 6 -C 18 )aryl; and
the mole ratio of m to n is from about 120:1 to about 40:1; and
wherein the crosslinked potassium binding polymer is characterized by a crosslinking of less than 5%.

2 . The crosslinked potassium binding polymer of claim 1 , wherein the ratio of m to n is from about 70:1 to about 50:1.

3 . The crosslinked potassium binding polymer of claim 1 or 2 , wherein the ratio of m to n is from about 70:1 to about 60:1.

4 . The crosslinked potassium binding polymer of any one of claims 1 to 3 , wherein the ratio of m to n is about 68:1.

5 . The crosslinked potassium binding polymer of any one of claims 1 to 4 , wherein Y is phenyl.

6 . The crosslinked potassium binding polymer of any one of claims 1 to 5 , wherein X is absent or phenyl.

7 . The crosslinked potassium binding polymer of any one of claims 1 to 6 , wherein X is absent and R 1 is H when XR 1 is attached to the carbon atom substituted with Y.

8 . The crosslinked potassium binding polymer of any one of claims 1 to 7 , wherein R 3 is H.

9 . The crosslinked potassium binding polymer of any one of claims 1 to 6 and 8 , wherein R 1 and R 2 are each independently H or —S(O) 2 OH.

10 . The crosslinked potassium binding polymer of any one of claims 1 to 9 , 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.

11 . The crosslinked potassium binding polymer of any one of claims 1 to 10 , 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.

12 . The crosslinked potassium binding polymer of any one of claims 1 to 11 , wherein the potassium binding polymer is characterized by a swelling ratio in water of about 3.3 grams of water per gram of polymer.

13 . The crosslinked potassium binding polymer of any one of claims 1 to 11 , wherein the potassium binding polymer is characterized by a swelling ratio in water of about 4.3 grams of water per gram of polymer.

14 . The crosslinked potassium binding polymer of any one of claims 1 to 13 , wherein the potassium binding polymer further comprises substantially spherical particles having a median diameter from about 5 μm to about 130 μm.

15 . The crosslinked potassium binding polymer of claim 14 , wherein the particles have an average particle size Dv(0.9) between about 80 μm to about 130 μm.

16 . The crosslinked potassium binding polymer of claim 14 or 15 , wherein the particles have an average particle size Dv(0.9) between about 90 μm to about 120 μm.

17 . The crosslinked potassium binding polymer of claim 14 , wherein the particles have an average particle size Dv(0.9) between about 40 μm to about 70 μm.

18 . The crosslinked potassium binding polymer of claim 14 or 17 , wherein the particles have an average particle size Dv(0.9) between about 50 μm to about 60 μm.

19 . The crosslinked potassium binding polymer of any one of claims 14 to 18 , wherein the particles have an average particle size Dv(0.5) between about 60 μm to about 90 μm.

20 . The crosslinked potassium binding polymer of any one of claims 14 to 19 , wherein the particles have an average particle size Dv(0.5) between about 70 μm to about 80 μm.

21 . The crosslinked potassium binding polymer of any one of claims 14 to 18 , wherein the particles have an average particle size Dv(0.5) between about 20 μm to about 50 μm.

22 . The crosslinked potassium binding polymer of any one of claims 14 to 18 and 21 , wherein the particles have an average particle size Dv(0.5) between about 30 μm to about 40 μm.

23 . The crosslinked potassium binding polymer of any one of claims 14 to 22 , wherein the particles have an average particle size Dv(0.1) between about 20 μm to about 70 μm.

24 . The crosslinked potassium binding polymer of any one of claims 14 to 23 , wherein the particles have an average particle size Dv(0.1) between about 30 μm to about 60 μm.

25 . The crosslinked potassium binding polymer of any one of claims 14 to 22 , wherein the particles have an average particle size Dv(0.1) between about 5 μm to about 30 μm.

26 . The crosslinked potassium binding polymer of any one of claims 14 to 22 and 25 , wherein the particles have an average particle size Dv(0.1) between about 6 μm to about 23 μm.

27 . The crosslinked potassium binding polymer of any one of claims 1 to 26 , 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.

28 . The crosslinked potassium binding polymer of any one of claims 1 to 27 , 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.

29 . The crosslinked potassium binding polymer of any one of claims 1 to 28 , wherein the potassium binding polymer has a potassium exchange capacity from about 1 mEq to about 4 mEq per gram of potassium binding polymer.

30 . The crosslinked potassium binding polymer of any one of claims 1 to 29 , wherein the potassium binding polymer has a Mouth Feel score greater than 3.5.

31 . The crosslinked potassium binding polymer of any one of claims 1 to 30 , wherein the potassium binding polymer has a Mouth Feel score greater than 4.5.

32 . The crosslinked potassium binding polymer of any one of claims 1 to 31 , wherein the potassium binding polymer has a Mouth Feel score greater than 5.0.

33 . The crosslinked potassium binding polymer of any one of claims 1 to 32 , wherein the potassium binding polymer is characterized by a crosslinking of less than 3%.

34 . The crosslinked potassium binding polymer of any one of claims 1 to 33 , wherein the potassium binding polymer is characterized by a crosslinking of about 1.8%, wherein the t

Assignees

• Ardelyx Inc

Inventors

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

Classifications

• A61P7/08

  Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock (artificial tears A61P27/04) · CPC title

• A61P3/12

  for electrolyte homeostasis · CPC title

• A61K9/1617

  Organic compounds, e.g. phospholipids, fats · CPC title

• C08F8/36 Primary

  Sulfonation; Sulfation · CPC title

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title