Crosslinked amine polymers

Abstract

The present invention provides methods and compositions for the treatment of ion imbalances. In particular, the invention provides polymeric and pharmaceutical compositions comprising crosslinked amine polymers. 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 renal diseases and hyperphosphatemia.

1. A polymeric composition comprising a crosslinked amine polymer, wherein said polymer comprises a crosslinked amine, said amine being at least one of 
                 
 
       and said amine being crosslinked with a crosslinking agent, wherein the crosslinking agent is a compound having at least two functional groups, each functional group being selected from halogen and epoxy. 
     
     
       2. A polymeric composition comprising a crosslinked amine polymer, the polymer comprising a crosslinked amine, the amine having the formula 
                 
 
       wherein n is 3, 4 or 5, and the amine is crosslinked with a crosslinking agent, wherein the crosslinking agent is a compound having at least two functional groups, each functional group selected from halogen and epoxy. 
     
     
       3. The polymeric composition of  claim 2  wherein n is 3. 
     
     
       4. The polymeric composition of  claim 2  wherein n is 5. 
     
     
       5. A polymeric composition comprising a crosslinked amine polymer, the polymer comprising a crosslinked amine, the amine having the formula 
                 
 
       wherein the amine is crosslinked with a crosslinking agent, wherein the crosslinking agent is a compound having at least two functional groups, each functional group selected from halogen and epoxy. 
     
     
       6. The polymeric composition of  claim 1  wherein the crosslinking agent is a compound having at least two functional groups, each functional group being selected from halogen, carbonyl, epoxy, ester, acid anhydride, acid halide, isocyanate, vinyl, and chloroformate. 
     
     
       7. The polymeric composition of  claim 1  wherein the crosslinking agent is epichlorohydrin. 
     
     
       8. The polymeric composition of  claim 1  wherein the molar ratio of crosslinking agent to amine ranges from about 0.2 to about 10. 
     
     
       9. The polymeric composition of  claim 1  wherein the molar ratio of crosslinking agent to amine ranges from about 0.5 to about 5. 
     
     
       10. The polymeric composition of  claim 1  wherein the crosslinked amine polymer is insoluble in a physiological isotonic buffer. 
     
     
       11. The polymeric composition of  claim 1  wherein the crosslinked amine polymer has a swelling ratio in physiological isotonic buffer ranging from about 1.2 to about 100. 
     
     
       12. The polymeric composition of  claim 1  wherein the crosslinked amine polymer has a swelling ratio in physiological isotonic buffer ranging from about 2 to 20. 
     
     
       13. The polymeric composition of  claim 1  wherein the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 0.5 mmol/g to about 10 mmol/g. 
     
     
       14. The polymeric composition of  claim 1  wherein the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 2.5 mmol/g to about 8 mmol/g. 
     
     
       15. The polymeric composition of  claim 1  wherein the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 3 mmol/g to about 6 mmol/g. 
     
     
       16. The polymeric composition of  claim 1  wherein the crosslinked amine polymer is a copolymer comprising several different amines as crosslinked amine moieties. 
     
     
       17. The polymeric composition of  claim 1  wherein the crosslinked amine polymer is a copolymer further comprising a diamine, a triamine or a tetramine as crosslinked amine moieties. 
     
     
       18. The polymeric composition of  claim 1  wherein the crosslinked amine polymer is a copolymer further comprising a diamine as crosslinked amine moieties. 
     
     
       19. The polymeric composition of  claim 1  wherein the crosslinked amine polymer is a copolymer further comprising 1,3-diaminopropane as crosslinked amine moieties. 
     
     
       20. The polymeric composition of  claim 5  wherein the crosslinked agent is epichlorohydrin, the molar ratio of crosslinking agent to amine ranges from about 0.2 to about 5, the crosslinked amine polymer is insoluble in a physiological isotonic buffer, the crosslinked amine polymer has a swelling ratio in physiological isotonic buffer ranging from about 2 to 20, and the crosslinked amine polymer has a binding capacity in a non-interfering buffer ranging from about 2.5 mmol/g to about 8 mmol/g. 
     
     
       21. A polymeric composition comprising a crosslinked amine polymer in bead form , the crosslinked amine polymer comprising repeat units derived from polymerization of an amine and a crosslinking agent, the amine having the formula 
                 
 
       wherein n is 3, 4 or  5 and the crosslinked amine polymer is in a bead form.    
     
     
       22. The polymeric composition of  claim 21  wherein the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 0.5 mmol/g to about 10 mmol/g. 
     
     
       23. The polymeric composition of  claim 21  wherein the molar ratio of crosslinking agent to amine ranges from about 0.2 to about 10, the crosslinked amine polymer is insoluble in a physiological isotonic buffer, the crosslinked amine polymer has a swelling ratio in physiological isotonic buffer ranging from about 2 to 20, and the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 0.5 mmol/g to about 10 mmol/g. 
     
     
       24. The polymeric composition of  claim 21  wherein n is 3. 
     
     
       25. The polymeric composition of  claim 21  wherein n is 4. 
     
     
       26. The polymeric composition of  claim 21  wherein n is 5. 
     
     
       27. The polymeric composition of  claim 22  wherein n is 3. 
     
     
       28. The polymeric composition of  claim 22  wherein n is 4. 
     
     
       29. The polymeric composition of  claim 22  wherein n is 5. 
     
     
       30. The polymeric composition of  claim 23  wherein n is 3. 
     
     
       31. The polymeric composition of  claim 23  wherein n is 4. 
     
     
       32. The polymeric composition of  claim 23  wherein n is 5. 
     
     
       33. The polymeric composition as recited in  of  claim 2  wherein said  the crosslinking agent is 1,3-dichloropropane or epichlorohydrin. 
     
     
       34. The polymeric composition of  claim 2  wherein the crosslinking agent is epichlorohydrin. 
     
     
       35. The polymeric composition of  claim 2  wherein the molar ratio of crosslinking agent to amine ranges from about 0.2 to about 10. 
     
     
       36. The polymeric composition of  claim 2  wherein the molar ratio of crosslinking agent to amine ranges from about 0.5 to about 5. 
     
     
       37. The polymeric composition of  claim 2  wherein the crosslinked amine polymer is insoluble in a physiological isotonic buffer. 
     
     
       38. The polymeric composition of  claim 2  wherein the crosslinking agent is a compound having at least two functional groups, each functional group being selected from halogen, carbonyl, epoxy, ester, acid anhydride, acid halide, isocyanate, vinyl, and chloroformate. 
     
     
       39. The polymeric composition of  claim 2  wherein the crosslinked amine polymer has a swelling ratio in physiological isotonic buffer ranging from about 1.2 to about 100. 
     
     
       40. The polymeric composition of  claim 2  wherein the crosslinked amine polymer has a swelling ratio in physiological isotonic buffer ranging from about 2 to 20. 
     
     
       41. The polymeric composition of  claim 2  wherein the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 0.5 mmol/g to about 10 mmol/g. 
     
     
       42. The polymeric composition of  claim 2  wherein the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 2.5 mmol/g to about 8 mmol/g. 
     
     
       43. The polymeric composition of  claim 2  wherein the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 3 mmol/g to about 6 mmol/g. 
     
     
       44. The polymeric composition of  claim 2  wherein the crosslinked amine polymer is a copolymer comprising several different amines as crosslinked amine moieties. 
     
     
       45. The polymeric composition of  claim 2  wherein the crosslinked amine polymer is a copolymer further comprising a diamine, a triamine or a tetramine as crosslinked amine moieties. 
     
     
       46. The polymeric composition of  claim 2  wherein the crosslinked amine polymer is a copolymer further comprising a diamine as a crosslinked amine moieties. 
     
     
       47. The polymeric composition of  claim 2  wherein the crosslinked amine polymer is a copolymer further comprising 1,3-diaminopropane as crosslinked amine moieties. 
     
     
       48. The polymeric composition as recited in  of  claim 5  wherein said  the crosslinking agent is 1,3-dichloropropane or epichlorohydrin. 
     
     
       49. The polymeric composition of  claim 5  wherein the crosslinking agent is a compound having at least two functional groups, each functional group being selected from halogen, carbonyl, epoxy, ester, acid anhydride, acid halide, isocyanate, vinyl, and chloroformate. 
     
     
       50. The polymeric composition of  claim 5  wherein the crosslinking agent is epichlorohydrin. 
     
     
       51. The polymeric composition of  claim 5  wherein the molar ratio of crosslinking agent to amine ranges from about 0.2 to about 10. 
     
     
       52. The polymeric composition of  claim 5  wherein the molar ratio of crosslinking agent to amine ranges from about 0.5 to about 5. 
     
     
       53. The polymeric composition of  claim 5  wherein the crosslinked amine polymer is insoluble in a physiological isotonic buffer. 
     
     
       54. The polymeric composition of  claim 5  wherein the crosslinked amine polymer has a swelling ratio in physiological isotonic buffer ranging from about 1.2 to about 100. 
     
     
       55. The polymeric composition of  claim 5  wherein the crosslinked amine polymer has a swelling ratio in physiological isotonic buffer ranging from about 2 to 20. 
     
     
       56. The polymeric composition of  claim 5  wherein the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 0.5 mmol/g to about 10 mmol/g. 
     
     
       57. The polymeric composition of  claim 5  wherein the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 2.5 mmol/g to about 8 mmol/g. 
     
     
       58. The polymeric composition of  claim 5  wherein the crosslinked amine polymer has a phosphate binding capacity in a non-interfering buffer ranging from about 3 mmol/g to about 6 mmol/g. 
     
     
       59. The polymeric composition of  claim 5  wherein the crosslinked amine polymer is a copolymer comprising several different amines as crosslinked amine moieties. 
     
     
       60. The polymeric composition of  claim 5  wherein the crosslinked amine polymer is a copolymer further comprising a diamine, a triamine or a tetramine as crosslinked amine moieties. 
     
     
       61. The polymeric composition of  claim 5  wherein the crosslinked amine polymer is a copolymer further comprising a diamine as crosslinked amine moieties. 
     
     
       62. The polymeric composition of  claim 5  wherein the crosslinked amine polymer is a copolymer further comprising 1,3-diaminopropane as crosslinked amine moieties. 
     
     
       63. The polymeric composition of  claim 2  wherein the polymeric composition consists essentially of the polymerization product of the amine corresponding to the structure 
                 
 
       wherein n is  3 ,  4  or  5 ; and a crosslinking agent, wherein n is 3, 4, or 5 . 
     
     
       64. The polymeric composition of  claim 63  wherein the crosslinking agent is epichlorohydrin. 
     
     
       65. The polymeric composition of  claim 63  wherein the crosslinking agent is 1,3-dichloropropane. 
     
     
       66. The polymeric composition of  claim 63  wherein the polymeric composition consists essentially of the polymerization product derived from crosslinking the amine with the crosslinking agent using a molar ratio of crosslinking agent to amine ranging from about 0.5 to about 5. 
     
     
       67. The polymeric composition of  claim 2  wherein the polymeric composition consists essentially of the polymerization product of the amine corresponding to the structure 
                 
 
       and a crosslinking agent, the crosslinking agent being epichlorohydrin. 
     
     
       68. The polymeric composition as recited in  of  claim 1  wherein said  the crosslinking agent is 1,3-dichloropropane or epichlorohydrin. 
     
     
       69. A crosslinked amine polymer consisting essentially of repeat units derived from the polymerization of an amine monomer of formula 
                   
       
         wherein n is  3 ,  4  or  5 ; and a crosslinking agent. 
       
     
     
       70. The crosslinked amine polymer of  claim 69  wherein n is  3 . 
     
     
       71. The crosslinked amine polymer of  claim 69  wherein n is  4 . 
     
     
       72. The crosslinked amine polymer of  claim 69  wherein n is  5 . 
     
     
       73. The crosslinked amine polymer of  claim 69  wherein the crosslinking agent is epichlorohydrin. 
     
     
       74. The crosslinked amine polymer of  claim 69  wherein the crosslinking agent is  1 , 3 - dichloropropane.   
     
     
       75. A crosslinked amine polymer consisting of repeat units derived from the polymerization of an amine monomer of formula 
                   
       
         wherein n is  3 ,  4  or  5 ; and a crosslinking agent. 
       
     
     
       76. The crosslinked amine polymer of  claim 75  wherein n is  3 . 
     
     
       77. The crosslinked amine polymer of  claim 75  wherein n is  4 . 
     
     
       78. The crosslinked amine polymer of  claim 75  wherein n is  5 . 
     
     
       79. The crosslinked amine polymer of  claim 75  wherein the crosslinking agent is epichlorohydrin. 
     
     
       80. The crosslinked amine polymer of  claim 75  wherein the crosslinking agent is  1 , 3 - dichloropropane.   
     
     
       81. The crosslinked amine polymer of  claim 75  wherein n is  4  and the crosslinking agent is epichlorohydrin.