Details for Patent: 9,662,352

Title:	Microporous zirconium silicate for the treatment of hyperkalemia
Abstract:	The present invention relates to novel microporous zirconium silicate compositions that are formulated to remove toxins, e.g. potassium ions, from the gastrointestinal tract at an elevated rate without causing undesirable side effects. The preferred formulations are designed avoid increase in pH of urine in patients and/or avoid potential entry of particles into the bloodstream of the patient. Also disclosed is a method for preparing high purity crystals of UZSi-9 exhibiting an enhanced level of potassium exchange capacity. These compositions are particularly useful in the therapeutic treatment of hyperkalemia.
Inventor(s):	Keyser; Donald Jeffrey (Southlake, TX), Guillem; Alvaro F. (Lantana, TX)
Assignee:	ZS PHARMA, INC. (Coppell, TX)
Filing Date:	Jul 01, 2014
Application Number:	14/321,634
Claims:	1. A particulate cation exchange composition comprising a zirconium silicate of formula (I): A.sub.pM.sub.xZr.sub.1-xSi.sub.nGe.sub.yO.sub.m (I), in the ZS-1 form, where A is a potassium ion, hydronium ion or mixtures thereof, M is at least one framework metal, wherein the framework metal is hafnium (4+), tin (4+), niobium (5+), titanium (4+), cerium (4+), germanium (4+), praseodymium (4+), terbium (4+) or mixtures thereof, "p" has a value from about 1 to about 20, "x" has a value from 0 to less than 1, "n" has a value from about 0 to about 12, "y" has a value from 0 to about 12, "m" has a value from about 3 to about 36 and 1.ltoreq.n+y.ltoreq.12, wherein the particles exhibit a uniform microporous structure and a median particle size of greater than 3 microns and less than 7% of the particles in the composition have a diameter less than 3 microns. 2. The composition of claim 1, wherein 4% of the particles in the composition have a diameter less than 3 microns. 3. The composition of claim 1, wherein less than 1% of the particles in the composition have a diameter less than 3 microns. 4. The composition of claim 1, wherein the median particle size ranges from 5 to 1000 microns. 5. The composition of claim 1, wherein the median particle size ranges from 20 to 100 microns. 6. The composition of claim 1, wherein the zirconium silicate exhibits an X-ray powder diffraction pattern generated using a copper K-alpha radiation source of: TABLE-US-00008 d(.ANG.) 7.7-8.6 6.3-7.0 5.5-6.3 4.7-5.5 3.2-4.0 2.6-3.4. 7. The composition of claim 1, wherein the zirconium silicate is protonated. 8. A pharmaceutical composition product comprising the composition of claim 1 in capsule or tablet form. 9. A particulate cation exchange composition comprising a zirconium silicate of formula (I): A.sub.pM.sub.xZr.sub.1-xSi.sub.nGe.sub.yO.sub.m (I) in the ZS-9 form and in the ZS-1 form where A is a potassium ion, hydronium ion or mixtures thereof, M is at least one framework metal, wherein the framework metal is hafnium (4+), tin (4+), niobium (5+), titanium (4+), cerium (4+), germanium (4+), praseodymium (4+), terbium (4+) or mixtures thereof, "p" has a value from about 1 to about 20, "x" has a value from 0 to less than 1, "n" has a value from about 0 to about 12, "y" has a value from 0 to about 12, "m" has a value from about 3 to about 36 and 1.ltoreq.n+y.ltoreq.12, wherein the particles exhibit a uniform microporous structure and a median particle size of greater than 3 microns and less than 7% of the particles in the composition have a diameter less than 3. 10. The composition of claim 9, wherein the ZS-9 form exhibits an X-ray powder diffraction pattern generated using a copper K-alpha radiation source of: TABLE-US-00009 d(.ANG.) 5.9-6.7 5.3-6.1 2.7-3.5 2.0-2.8 1.6-2.4 and the ZS-1 form exhibits an X-ray powder diffraction pattern of: TABLE-US-00010 d(.ANG.) 7.7-8.6 6.3-7.0 5.5-6.3 4.7-5.5 3.2-4.0 2.6-3.4. 11. A pharmaceutical composition product comprising the composition of claim 9 in capsule or tablet form. 12. A method of removing excess serum ammonium ions comprising administering to a subject in need thereof an amount of the composition of claim 1. 13. The method of claim 12, wherein the amount administered is a dose of approximately 0.7 to 1,500 mg/Kg/day. 14. The method of claim 12, wherein the amount administered is a dose of approximately 500 to 1,000 mg/Kg/day. 15. The method of claim 12, wherein the amount administered is a dose of approximately 700 mg/Kg/day. 16. The method of claim 12, wherein the subject also exhibits excess serum potassium levels. 17. The method of claim 12, wherein the ZS-1 is protonated. 18. A method of treating hyperammonemia comprising administering to a subject in need thereof an effective amount of the composition of claim 1 to treat the subject. 19. The method of claim 12, wherein the subject also suffers from hyperkalemia. 20. The method of claim 19, wherein the hyperkalemia is acute hyperkalemia. 21. The method of claim 19, wherein the hyperkalemia is chronic or sub-acute hyperkalemia. 22. The method of claim 12, further comprising administering a ZS-9. 23. The method of claim 22, wherein the ZS-9 exhibits a median particle size of greater than 3 microns and less than 7% of the particles in the composition have a diameter less than 3 microns, and the composition exhibits a sodium content below 12% by weight.