Method of synthesizing zirconium phosphate particles

• US 7,566,432 B2
• Filed: 12/14/2005
• Issued: 07/28/2009
• Est. Priority Date: 12/28/2004
• Status: Expired due to Fees

• Current Assignee: Renal Solutions, Inc. (Fresenius Medical Care AG)
• Original Assignee: Renal Solutions, Inc. (Fresenius Medical Care AG)
• Inventors: Wong, Raymond
• Primary Examiner(s): LANGEL, WAYNE A
• Application Number:
  US11/302,757
• Publication Number:
  US 20060140840A1
• Time in Patent Office: 1,322 Days
• Field of Search: 423305-312
• US Class Current: 423/305
• CPC Class Codes: A61K 33/42 Phosphorus; Compounds thereof
• CPC Class Codes: B01J 20/0211 Compounds of Ti, Zr, Hf
• CPC Class Codes: B01J 20/0292 Phosphates of compounds other than those provided for in B01J20/048
• CPC Class Codes: B01J 2220/62 In a cartridge
• CPC Class Codes: B01J 27/16 containing oxygen , i.e. acids, anhydrides and their derivates with N, S, B or halogens without carriers or on carriers based on C, Si, Al or Zr; also salts of Si, Al and Zr
• CPC Class Codes: B01J 37/031 Precipitation
• CPC Class Codes: B01J 39/12 Compounds containing phosphorus
• CPC Class Codes: C01B 25/372 of titanium, vanadium, zirconium, niobium, hafnium or tantalum
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

Zirconium phosphate particles are synthesized by providing a solution of zirconium oxychloride in an aqueous solvent, adding at least one oxygen-containing additive to the solution, the oxygen-containing additive being selected to form a complex with zirconium ions in the solution of zirconium oxychloride and thereby reduce hydration of the zirconium ions, and combining this solution with phosphoric acid or a phosphoric acid salt to obtain zirconium phosphate particles by sol gel precipitation.

Claims

1. A method of making zirconium phosphate particles comprising:

(a) combining at least one oxygen-containing additive with zirconium oxychloride in an aqueous solvent to form a solution wherein the oxygen-containing additive forms a complex with zirconium ions in the solution, and

(b) combining the solution obtained in (a) with phosphoric acid or a phosphoric acid salt to obtain zirconium phosphate particles by sol gel precipitation,

wherein said zirconium oxychloride and said phosphoric acid are introduced at a molar ratio of zirconium oxychloride to phosphoric acid of 1;

2.8 to 1;

3.2.

2. The method of claim 1, wherein the aqueous solvent is deionized water or RO water.

3. The method of claim 1, wherein zirconium oxychloride is dissolved in the aqueous solvent and then the oxygen-containing additive is added to form the solution of step (a).

4. The method of claim 3, wherein the zirconium oxychloride is present in the aqueous solvent at a saturation concentration.

5. The method of claim 1, wherein the oxygen-containing additive is dissolved in the aqueous solvent and then the zirconium oxychloride is added to form the solution of step (a).

6. The method of claim 1, wherein the oxygen-containing additive is present in the solution of step (a) in a molar amount sufficient so that substantially all of the zirconium ions in the solution are converted to a complex.

7. The method of claim 1, wherein the oxygen-containing additive forms a soluble polymer with zirconium ions.

8. The method of claim 1, wherein the oxygen-containing additive is an inorganic sulfate, a inorganic carbonate, an alcohol, a carboxylate, a ketone, an aldehyde, an organic sulfate, or combinations thereof.

9. The method of claim 1, wherein the oxygen-containing additive is sulfuric acid, sodium sulfate, sodium carbonate, isopropanol, glycerol, sodium lauryl sulfate, tartaric acid, polyvinyl alcohol, 2-amino-2-methyl-propanol, hydroxypropyl cellulose, tetrasodium N-(1 ,2-dicarboxyethyl)-N-octadecyl sulfosuccinamate, octylphenoxypolyethoxy(9-10)ethanol, polyethoxylated(20) oleyl alcohol, ethylenediamine alkoxylate block copolymer, or combinations thereof.

10. The method of claim 1, wherein the oxygen-containing additive is a combination of sodium sulfate and glycerol, a combination of sodium sulfate and sodium lauryl sulfate, a combination of sodium sulfate and tartaric acid, or a combination of sodium sulfate and tetrasodium N-(1,2-dicarboxyethyl)-N-octadecyl sulfosuccinamate, or combinations thereof.

11. The method of claim 1, wherein in step (b), to accomplish the combining of the solution obtained in step (a) with phosphoric acid or phosphoric acid salt, a phosphoric acid solution is titrated to a pH of from about 1 to about 4 and then combined with the solution obtained in step (a).

12. The method of claim 11, wherein the phosphoric acid solution is titrated by adding NaOH to the phosphoric acid solution until a pH of from about 1 to about 4 is obtained.

13. The method of claim 1, wherein in step (b), the solution obtained in step (a) and a solution of phosphoric acid or phosphate are combined so that zirconium ions and phosphate groups are present in a molar ratio of 1 to 3 of zirconium to phosphate.

14. The method of claim 1, wherein in carrying out step (b), the solution of step (a) and the phosphoric acid or phosphate are combined by providing a solution of phosphoric acid in an aqueous solution and adding at least part of the solution of step (a) and at least part of the solution of phosphoric acid simultaneously to a reaction vessel so that the concentration of phosphoric acid is kept constant in the reaction vessel during a period of time that the phosphoric acid is added to the reaction vessel.

15. The method of claim 14, wherein the reaction vessel includes an agitator.

16. The method of claim 1, wherein in carrying out step (b) to obtain the zirconium phosphate particles by sol gel precipitation, a slurry containing at least a zirconium phosphate gel precipitate is formed, and wherein the slurry is agitated.

17. The method of claim 16, wherein the slurry is titrated to a pH of from about 1 to about 2.

18. The method of claim 16, wherein the slurry is titrated to a pH of from about 1 to about 2 by adding NaOH to the slurry.

19. The method of claim 1, further comprising isolating and drying the zirconium phosphate particles obtained in step (b) to obtain a free flowing powder.

20. The method of claim 1, wherein steps (a) to (b) take place at a temperature of from 20°

C. to 35°

C.

21. The method of claim 1, wherein in step (b), the solution obtained in step (a) is combined with phosphoric acid by providing a reaction vessel and simultaneously adding the solution obtained in step (a) and a diluted solution of phosphoric acid to the reaction vessel.

22. The method of claim 1, wherein steps (a) and (b) take place at ambient temperature, and

(c) subjecting an aqueous slurry containing zirconium phosphate particles obtained from (b) to a heat treatment above ambient temperature.

23. The method of claim 22, wherein the heat treatment is carried out at a temperature of from about 180 to about 185°

F.

24. The method of claim 22, wherein the heat treatment of (c) is carried out for at least one hour.

25. The method of claim 22, wherein the aqueous slurry of (c) is agitated during the heat treatment.

26. The method of claim 22, wherein between (b) and (c), the zirconium phosphate particles obtained in (b) are subjected to washing and filtration before being combined with an aqueous solvent to form the aqueous slurry.

27. The method of claim 22, wherein, after (c), the aqueous slurry is titrated to a pH of about 5.75 to about 6.25.

28. The method of claim 27, wherein the titrated slurry is subjected to washing, filtration, and drying to obtain zirconium phosphate particles as a free-flowing powder.

29. The method of claim 1, wherein said zirconium phosphate particles obtained have a particle size distribution of less than 20% in the range of >

60-120 microns, more than 80% in the range of 30-60 microns, and less than 10% in the range of less than 30 microns,

an ammonia capacity of 15-20 mg NH₄-N/gm ZP, and

an Na⁺ content of 3.8-6.2 wt%, based on the weight of the zirconium phosphate particles.

30. The method of claim 29, wherein said ammonia capacity is 16-17 mg NH₄-N/gm ZP.

31. A method of making zirconium phosphate particles comprising:

adding a solution of zirconium oxychloride and a solution of phosphoric acid simultaneously to a reaction vessel to obtain zirconium phosphate particles by sol gel precipitation.

32. The method of claim 31, wherein the solution of zirconium oxychloride is added to the reaction vessel through at least one spray head.

33. The method of claim 32, wherein the solution of zirconium oxychloride is in the form of droplets before it is combined with the solution of phosphoric acid.

34. The method of claim 31, wherein the reaction vessel includes an agitator.

35. The method of claim 34, wherein the agitator comprises a shaft having a plurality of blades attached to the shaft at different levels.

36. A method of making zirconium phosphate particles having a controlled particle size comprising:

forming zirconium phosphate particles by sol gel precipitation by the method of claim 31,

and controlling at least one of the following parameters to affect particle size or particle size distribution of the zirconium phosphate particles;

rate at which the solution of zirconium oxychloride is added to the reaction vessel, rate at which the solution of phosphoric acid or phosphoric acid salt is added to the reaction vessel, pH of the solution of phosphoric acid or phosphoric acid salt, concentration of zirconium oxychloride and phosphoric acid or phosphoric acid salt in the reaction vessel, or speed of the agitator, or combinations thereof.

37. A method of making zirconium phosphate particles comprising:

(a) combining at least one oxygen-containing additive with zirconium oxychloride in an aqueous solvent to form a solution wherein the oxygen-containing additive forms a complex with zirconium ions in the solution, and

(b) combining the solution obtained in (a) with phosphoric acid or a phosphoric acid salt to obtain zirconium phosphate particles by sol gel precipitation,

wherein the oxygen-containing additive is sulfuric acid, sodium sulfate, sodium carbonate, isopropanol, glycerol, sodium lauryl sulfate, tartaric acid, polyvinyl alcohol, 2-amino-2-methyl-propanol, hydroxypropyl cellulose, tetrasodium N-( 1,2-dicarboxyethyl)-N-octadecyl sulfosuccinamate, octylphenoxypolyethoxy(9-10)ethanol, polyethoxylated(20) oleyl alcohol, ethylenediamine alkoxylate block copolymer, or combinations thereof.

38. A zirconium phosphate composition comprising a water-soluble zirconium phosphate polymer in an aqueous solution, wherein the polymer is formed by combining, in an aqueous solvent, zirconium oxychloride with at least one oxygen-containing additive that is capable of forming a complex with zirconium ions, wherein said zirconium phosphate composition, when dried, has a particle size distribution of less than 20% in the range of >

60-120 microns, more than 80% in the range of 30-60 microns, and less than 10% in the range of less than 30 microns,

an ammonia capacity of 15-20 mg NH₄-N/gm ZP, and

an Na⁺ content of 3.8-6.2 wt%, based on the weight of the zirconium phosphate particles.