Compositions and methods for treating hyperkalemia

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.

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 calcium salt of  claim 1 , wherein the ratio of m to n is from about 70:1 to about 50:1 or from about 70:1 to about 60:1. 
     
     
         3 .- 4 . (canceled) 
     
     
         5 . The calcium salt of  claim 1 , wherein Y is phenyl. 
     
     
         6 . The calcium salt of  claim 1 , wherein X is absent or phenyl. 
     
     
         7 . The calcium salt of  claim 1 , wherein X is absent and R 1  is H when XR 1  is attached to the carbon atom substituted with Y. 
     
     
         8 . The calcium salt of  claim 1 , wherein R 3  is H. 
     
     
         9 . The calcium salt of  claim 1 , wherein R 1  and R 2  are each independently H or —S(O) 2 OH. 
     
     
         10 . Them calcium salt of  claim 1 , wherein the potassium binding polymer is characterized by a swelling ratio in water of from about 3 grams of water per gram of polymer to about 8 grams of water per gram of polymer or from about 3 grams of water per gram of polymer to about 4.5 grams of water per gram of polymer. 
     
     
         11 .- 13 . (canceled) 
     
     
         14 . The calcium salt of  claim 1 , wherein the potassium binding polymer further comprises substantially spherical particles having a median diameter from about 5 m to about 130 m. 
     
     
         15 . The calcium salt of  claim 14 , wherein the particles have an average particle size Dv(0.9) from about 80 μm to about 130 μm or from about 90 μm to about 120 μm. 
     
     
         16 . (canceled) 
     
     
         17 . The calcium salt of  claim 14 , wherein the particles have an average particle size Dv(0.9) from about 40 μm to about 70 μm or from about 50 μm to about 60 μm. 
     
     
         18 . (canceled) 
     
     
         19 . The calcium salt of  claim 14 , wherein the particles have an average particle size Dv(0.5) from about 60 μm to about 90 μm or from about 70 μm to about 80 μm. 
     
     
         20 . (canceled) 
     
     
         21 . The calcium salt of  claim 14 , wherein the particles have an average particle size Dv(0.5) from about 20 μm to about 50 μm or from about 30 μm to about 40 μm. 
     
     
         22 . (canceled) 
     
     
         23 . The calcium salt of  claim 14 , wherein the particles have an average particle size Dv(0.1) from about 20 μm to about 70 μm or from about 30 μm to about 60 μm. 
     
     
         24 . (canceled) 
     
     
         25 . The calcium salt of  claim 14 , wherein the particles have an average particle size Dv(0.1) from about 5 μm to about 30 μm or from about 6 μm to about 23 μm. 
     
     
         26 . (canceled) 
     
     
         27 . The calcium salt 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. 
     
     
         28 . The calcium salt 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. 
     
     
         29 . The calcium salt 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. 
     
     
         30 . The calcium salt of  claim 1 , wherein the potassium binding polymer has a Mouth Feel score greater than 3.5. 
     
     
         31 .- 32 . (canceled) 
     
     
         33 . The calcium salt of  claim 1 , wherein the potassium binding polymer is characterized by a crosslinking of less than 3%. 
     
     
         34 .- 412 . (canceled)