Magnesium-ammonium-phosphates cements, the production of the same and the use thereof

• US 6,692,563 B2
• Filed: 03/04/2002
• Issued: 02/17/2004
• Est. Priority Date: 07/03/2000
• Status: Expired due to Term

• Current Assignee: Kyphon SARL (Medtronic Plc)
• Original Assignee: Kyphon Incorporated
• Inventors: Zimmermann, Michael
• Primary Examiner(s): Wood; Elizabeth D.
• Application Number:
  US10/070,670
• Publication Number:
  US 20020166480A1
• Time in Patent Office: 715 Days
• Field of Search: 106/35,690,691,696
• US Class Current: 106/696
• CPC Class Codes: A61B 17/00491 Surgical glue applicators surgical adhesives A61L24/00; two-component delivery syringes A61M5/19
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30535 Special structural features of bone or joint prostheses not otherwise provided for
• CPC Class Codes: A61F 2002/4631 the prosthesis being specially adapted for being cemented
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0058 Additional features; Implant or prostheses properties not otherwise provided for
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/42 Phosphorus; Compounds thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 6/17 Particle size
• CPC Class Codes: A61K 6/838 Phosphorus compounds, e.g. apatite
• CPC Class Codes: A61K 6/864 Phosphate cements apatite A61K6/838
• CPC Class Codes: A61K 6/867 Ammonium cements
• CPC Class Codes: A61L 24/0036 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 24/02 containing inorganic materials
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: C04B 12/025 : Phosphates of ammonium or of the alkali or alkaline earth metals
• CPC Class Codes: C04B 14/22 : Glass ; Devitrified glass
• CPC Class Codes: C04B 14/26 : Carbonates
• CPC Class Codes: C04B 14/30 : Oxides other than silica ferrites C04B14/363
• CPC Class Codes: C04B 14/304 : Magnesia
• CPC Class Codes: C04B 14/366 : Phosphates, e.g. apatite
• CPC Class Codes: C04B 20/008 : Micro- or nanosized fillers, e.g. micronised fillers with particle size smaller than that of the hydraulic binder colloidal silica C04B14/062 ; silica fume C04B18/146
• CPC Class Codes: C04B 2103/0009 : Inorganic ammonium compounds
• CPC Class Codes: C04B 2111/00206 : Compositions defined by their elemental analysis
• CPC Class Codes: C04B 2111/00836 : for medical or dental applications
• CPC Class Codes: C04B 22/06 : Oxides, Hydroxides C04B22/0013 takes precedence
• CPC Class Codes: C04B 22/062 : of the alkali or alkaline-earth metals
• CPC Class Codes: C04B 22/064 : of the alkaline-earth metals
• CPC Class Codes: C04B 22/10 : containing carbon in the anion
• CPC Class Codes: C04B 22/124 : Chlorides of ammonium or of the alkali or alkaline earth metals, e.g. calcium chloride
• CPC Class Codes: C04B 22/126 : Fluorine compounds, e.g. silico-fluorine compounds
• CPC Class Codes: C04B 22/142 : Sulfates
• CPC Class Codes: C04B 22/143 : Calcium-sulfate
• CPC Class Codes: C04B 22/16 : containing phosphorus in the anion, e.g. phosphates
• CPC Class Codes: C04B 24/10 : Carbohydrates or derivatives thereof
• CPC Class Codes: C04B 24/282 : Polyurethanes; Polyisocyanates
• CPC Class Codes: C04B 28/34 : containing cold phosphate binders
• CPC Class Codes: C04B 28/344 : the phosphate binder being present in the starting composition solely as one or more phosphates
• CPC Class Codes: C04B 28/346 : the phosphate binder being present in the starting composition as a mixture of free acid and one or more phosphates
• CPC Class Codes: C04B 28/348 : the starting mixture also containing one or more reactive oxides

Abstract

This invention relates to a cement, which consists in its main phase of microcrystalline magnesium ammonium phosphate and nanoapatite after hardening and thus at the same time has considerable strength.

The material is biologically degradable and is suitable for application in tooth cements, as bone replacement, as bone filler, as bone cement or as bone adhesive.

Claims

1. A magnesium ammonium phosphate cement preparation comprising

a powder mixture having molar quantities of the components calcium (Ca), magnesium (Mg) and orthophosphate (P) in the mixture in the ranges 1.00<

Ca/P<

1.50 and 0<

Mg/P<

0.50;

an ammonium salt; and

water or an aqueous solution.

2. The preparation according to claim 1, wherein the aqueous solution comprises an aqueous solution of an ammonium salt having a pH value in the range from 7<

pH<

12.

3. The preparation according to claim 1, wherein the ammonium salt is present in the powder mixture and the molar quantity of the component ammonium (NH₄) lies in the range 0<

NH₄<

0.50.

4. A preparation according to one of claim 1, wherein the powder mixture comprises α

/β

-tertiary calcium phosphate (α

/β

-TCP).

5. A preparation according to claim 4, wherein the powder mixture further comprises MgHPO₄.3H₂O.

6. The preparation according to claim 5, wherein the powder mixture further comprises Mg₃(PO₄)₂.

7. The preparation according to claim 1, wherein the aqueous solution comprises an aqueous (NH₄)₂SO₄ solution.

8. The preparation according to claim 1, wherein the powder mixture comprises (NH₄)₂SO₄.

9. The preparation according to claim 1, wherein the aqueous solution comprises an aqueous (NH₄)₂HPO₄ solution.

10. The preparation according to claim 1, wherein the powder mixture further comprises KH₂PO₄.

11. The preparation according to claim 1, wherein the powder mixture further comprises Na₂HPO₄.

12. The preparation according to claim 1, further comprising SrCO₃.

13. The preparation according to claim 12, wherein the SrCO₃ is in the range of 0 to 10 wt. % based on the total weight of the preparation.

14. The preparation according to claim 13, comprising an aqueous solution of an ammonium salt.

15. The preparation according to claim 12, wherein the SrCO₃ is in the range of 0.1 to 5 wt. % based on the total weight of the preparation.

16. The preparation according to claim 15, comprising an aqueous solution of an ammonium salt.

17. The preparation according to claim 1, wherein the aqueous solution comprises an aqueous solution of a strontium salt.

18. The preparation according to claim 1, further comprising ZnO.

19. The preparation according to claim 1, wherein the powder mixture further comprises Ca₂NaK(PO₄)₂ and/or CaKPO₄.

20. The preparation according to claim 1, further comprising a fluoride.

21. The preparation according to claim 1, further comprising a pharmaceutical and/or a bioactive active ingredient.

22. The preparation according to claim 21, wherein the pharmaceutical and/or a bioactive active ingredient comprises a therapeutic dose of a component selected from the group consisting of antibiotics, cytostatic agents, analgesics, disinfectants, growth factors, proteins or elastin inhibitors.

23. A magnesium ammonium phosphate cement preparation comprising:

a powder mixture comprising α

-TCP, β

-TCP, MgHPO₄.3 H₂O, KH₂PO₄ and Na₂HPO₄;

an ammonium salt; and

water or an aqueous solution.

24. The preparation according to claim 23, wherein the powder mixture further comprises SrCO₃.

25. The preparation according to claim 24, wherein the SrCO₃ is present in a quantity of 0.01 to 10 wt. % based on the total weight of the preparation.

26. The preparation according to claim 23, wherein the aqueous solution comprises an aqueous solution of a strontium salt.

27. The preparation according to claim 23, further comprising ZnO.

28. The preparation according to claim 23, wherein the powder mixture further comprises Ca₂NaK(PO₄)₂ and/or CaKPO₄.

29. The preparation according to claim 23, further comprising a fluoride.

30. The preparation according to claim 23, further comprising a pharmaceutical and/or a bioactive active ingredient.

31. The preparation according to claim 30, wherein the pharmaceutical and/or a bioactive active ingredient comprises a therapeutic dose of a component selected from the group consisting of antibiotics, cytostatic agents, analgesics, disinfectants, growth factors, proteins or elastin inhibitors.

32. A magnesium ammonium phosphate cement preparation comprising an aqueous solution containing ammonium ions and a powder mixture comprising α

/β

-TCP, MgHPO₄×

3H₂O, KH₂PO₄ Na₂HPO₄ and Mg₃(PO₄)₂.

33. The preparation according to claim 32, wherein the powder mixture further comprises SrCO₃.

34. The preparation according to claim 33, wherein the SrCO₃ is present in a quantity of 0.01 to 10 wt. % based on the total weight of the preparation.

35. The preparation according to claim 32, wherein the aqueous solution comprises an aqueous solution of a strontium salt.

36. The preparation according to claim 32, further comprising ZnO.

37. The preparation according to claim 32, wherein the powder mixture further comprises Ca₂NaK(PO₄)₂ and/or CaKPO₄.

38. The preparation according to claim 32, further comprising a fluoride.

39. The preparation according to claim 32, further comprising a pharmaceutical and/or a bioactive active ingredient.

40. The preparation according to claim 39, wherein the pharmaceutical and/or a bioactive active ingredient comprises a therapeutic dose of a component selected from the group consisting of antibiotics, cytostatic agents, analgesics, disinfectants, growth factors, proteins or elastin inhibitors.

41. A magnesium ammonium phosphate cement preparation comprising:

a powder mixture comprising α

-TCP, β

-TCP, (NH₄)₂SO₄, KH₂PO₄ and Na₂HPO₄;

a magnesium salt; and

water or an aqueous solution.

42. The preparation according to claim 41, wherein the magnesium salt is MgHPO₄.3H₂O.

43. The preparation according to claim 41, wherein the powder mixture further comprises SrCO₃.

44. The preparation according to claim 43, wherein the SrCO₃ is present in a quantity of 0.01 to 10 wt. % based on the total weight of the preparation.

45. The preparation according to claim 41, wherein the aqueous solution comprises an aqueous solution of a magnesium salt.

46. The preparation according to claim 41, wherein the aqueous solution comprises an aqueous solution of a strontium salt.

47. The preparation according to claim 41, further comprising ZnO.

48. The preparation according to claim 41, wherein the powder mixture further comprises Ca₂NaK(PO₄)₂ and/or CaKPO₄.

49. The preparation according to claim 41, further comprising a fluoride.

50. The preparation according to claim 41, further comprising a pharmaceutical and/or a bioactive active ingredient.

51. The preparation according to claim 50, wherein the pharmaceutical and/or a bioactive active ingredient comprises a therapeutic dose of a component selected from the group consisting of antibiotics, cytostatic agents, analgesics, disinfectants, growth factors, proteins or elastin inhibitors.

52. A magnesium ammonium phosphate cement preparation comprising:

a powder mixture comprising α

-TCP, β

-TCP, primary or secondary ammonium phosphate, KH₂PO₄ and Na₂HPO₄;

a magnesium salt; and

water or an aqueous solution.

53. The preparation according to claim 52, wherein the magnesium salt is MgHPO₄.3 H₂O.

54. The preparation according to claim 52, wherein the powder mixture further comprises SrCO₃.

55. The preparation according to claim 54, wherein the SrCO₃ is present in a quantity of 0.01 to 10 wt. % based on the total weight of the preparation.

56. The preparation according to claim 52, wherein the aqueous solution comprises an aqueous solution of a strontium salt.

57. The preparation according to claim 52, further comprising ZnO.

58. The preparation according to claim 52, wherein the powder mixture further comprises Ca₂NaK(PO₄)₂ and/or CaKPO₄.

59. The preparation according to claim 52, further comprising a fluoride.

60. The preparation according to claim 52, further comprising a pharmaceutical and/or a bioactive active ingredient.

61. The preparation according to claim 60, wherein the pharmaceutical and/or a bioactive active ingredient comprises a therapeutic dose of a component selected from the group consisting of antibiotics, cytostatic agents, analgesics, disinfectants, growth factors, proteins or elastin inhibitors.

62. A process for producing a magnesium ammonium phosphate cement, the process comprising:

providing an ammonium salt;

providing a powder mixture having molar quantities of the components calcium (Ca), magnesium (Mg) and orthophosphate (P) in the mixture in the ranges 1.00<

Ca/P<

1.50 and 0<

Mg/P<

0.50;

mixing the ammonium salt and the powder mixture with a mixing liquid to form a paste and achieve an uniform distribution of the liquid in the powder mixture; and

hardening the paste and reacting the components therein to form a microcrystalline magnesium ammonium phosphate.

63. The process according to claim 62, wherein the ammonium salt is provided in an aqueous solution and the mixing liquid comprises the aqueous solution of the ammonium salt.

64. The process according to claim 62, further comprising providing the powder mixture with granular particles, which are slightly soluble in aqueous liquids, having a particle size between about 10 μ

m and about 300 μ

m.

65. The process according to claim 64, wherein the granular particles are between 50 μ

m and 200 μ

m.

66. The process according to claim 64, further comprising selecting the granular particles from the group consisting of NaCl, sugars, CaSO₄, β

-TCP, polylactides, polyglycolides, polylactide/polyglycolide copolymers, CaCO₃ and CaHPO₄.

67. A process for producing a magnesium ammonium phosphate cement, the process comprising:

providing an ammonium salt;

providing a powder mixture having molar quantities of the components calcium (Ca), magnesium (Mg) and orthophosphate (P) in the mixture in the ranges 1.00<

Ca/P<

1.50 and 0<

Mg/P<

0.50;

mixing the ammonium salt and the powder mixture with a mixing liquid to form a paste and achieve an uniform distribution of the liquid in the powder mixture; and

hardening the paste with formation of a microcrystalline magnesium ammonium phosphate.

68. The process according to claim 67, wherein the ammonium salt is provided in an aqueous solution and the mixing liquid comprises the aqueous solution of the ammonium salt.

69. The process according to claim 67, further comprising providing the powder mixture with granular particles, which are slightly soluble in aqueous liquids, having a particle size between about 10 μ

m and about 300 μ

m.

70. The process according to claim 69, wherein the granular particles are between 50 μ

m and 200 μ

m.

71. The process according to claim 69, further comprising selecting the granular particles from the group consisting of NaCl, sugars, CaSO₄, β

-TCP, polylactides, polyglycolides, polylactide/polyglycolide copolymers, CaCO₃ and CaHPO₄.

72. A method for dentine or endodontology repair in a patient site, said method comprising applying a hardenable magnesium phosphate cement preparation to the patient site, wherein the preparation comprises:

a powder mixture having molar quantities of the components calcium (Ca), magnesium (Mg) and orthophosphate (P) in the mixture in the ranges 1.00<

Ca/P<

1.50 and 0<

Mg/P<

0.50;

an ammonium salt; and

water or an aqueous solution.

73. A method for bone replacement or repair in a patient site, said method comprising applying a hardenable magnesium phosphate cement preparation to the patient site, wherein the preparation comprises:

a powder mixture having molar quantities of the components calcium (Ca), magnesium (Mg) and orthophosphate (P) in the mixture in the ranges 1.00<

Ca/P<

1.50 and 0<

Mg/P<

0.50;

an ammonium salt; and

water or an aqueous solution.