Metabolic detoxification and method

• US 20050236329A1
• Filed: 02/23/2005
• Published: 10/27/2005
• Est. Priority Date: 04/27/2004
• Status: Active Grant

• Current Assignee: RH Cell Therapeutics Corporation
• Original Assignee: Vital Therapies, Inc. (Immunic, Inc.)
• Inventors: He, Dar, Brotherton, John D.
• Granted Patent: US 8,105,491 B2
• Time in Patent Office: Days
• US Class Current: 210/645
• CPC Class Codes: A61M 1/1694 with recirculating dialysing liquid
• CPC Class Codes: A61M 1/1698 Blood oxygenators with or without heat-exchangers intracorporal A61M1/1678; manufacturing of membranes therefor B01D67/00; semi-permeable membranes for separation processes characterised by their properties B01D69/00; semi-permeable membranes characterised by their material B01D71/00
• CPC Class Codes: A61M 1/3472 with treatment of the filtrate
• CPC Class Codes: A61M 1/3475 with filtrate treatment agent in the same enclosure as the membrane
• CPC Class Codes: A61M 1/3489 by biological cells, e.g. bioreactor
• CPC Class Codes: A61M 1/3623 Means for actively controlling temperature of blood

Abstract

An extracorporeal filtration and detoxification system and method generally comprise separating ultrafiltrate from cellular components of blood, treating the ultrafiltrate independently of the cellular components in a recirculation circuit, recombining treated ultrafiltrate and the cellular components, and returning whole blood to the patient. A recirculation circuit generally comprises an active cartridge including active cells operative to effectuate a selected treatment; in some embodiments, the active cells are the C3A cell line.

Claims

1. An extracorporeal filtration and detoxification method, comprising:

(a) drawing blood from a patient;

(b) separating ultrafiltrate fluid from cellular components of said blood;

(c) treating said ultrafiltrate independently of said cellular components in a recirculation circuit, wherein said treating comprises circulating said ultrafiltrate through an active cartridge comprising active cells operative to effectuate a selected treatment of said ultrafiltrate;

(d) recombining treated ultrafiltrate and said cellular components; and

(e) returning whole blood comprising said ultrafiltrate and said cellular components to the patient.

2. The method of claim 1, further comprising analyzing the composition of said ultrafiltrate subsequent to said separating.

3. The method of claim 1, wherein said drawing comprises utilizing a first lumen of a double lumen catheter and wherein said returning comprises utilizing a second lumen of said double lumen catheter.

4. The method of claim 1, wherein said drawing comprises utilizing a blood pump operative to circulate said blood from the patient, through an ultrafiltrate generator, and back to the patient at a selected flow rate.

5. The method of claim 1, wherein said separating comprises utilizing an ultrafiltrate generator comprising a hollow fiber filter cartridge.

6. The method of claim 5, wherein said utilizing comprises drawing said ultrafiltrate through a semi-permeable membrane of said hollow fiber filter cartridge.

7. The method of claim 6, wherein said semi-permeable membrane has a pore size of approximately 0.2 μ

m.

8. The method of claim 6, wherein said semi-permeable membrane has a pore size of approximately 0.1 μ

m.

9. The method of claim 6, wherein said semi-permeable membrane has a nominal molecular weight cut-off of about 100,000 Daltons.

10. The method of claim 6, wherein said drawing comprises implementing a ultrafiltrate pump.

11. The method of claim 1, further comprising infusing said blood with an anticoagulation agent.

12. The method of claim 1, further comprising infusing said ultrafiltrate with glucose.

13. The method of claim 1, wherein said treating further comprises infusing said ultrafiltrate with a promoter operative to enhance the activity of said active cells.

14. The method of claim 1, wherein said treating further comprises oxygenating said ultrafiltrate.

15. The method of claim 1, wherein said treating further comprises maintaining said ultrafiltrate at a predetermined temperature.

16. The method of claim 14, wherein said treating further comprises maintaining said ultrafiltrate at approximately 37°

C.

17. The method of claim 1, wherein said active cells are a subclone of the human hepatoblastoma cell line.

18. The method of claim 17, wherein said active cells are the C3A cell line.

19. The method of claim 1, further comprising filtering said ultrafiltrate prior to said recombining.

20. The method of claim 19, wherein said filtering comprises utilizing a hollow fiber filter.

21. The method of claim 19, wherein said filtering comprises utilizing one or more of a detoxification device, an ammonia trap, and a mechanical filter.

22. The method of claim 1, wherein said returning comprises detecting and removing gaseous contaminants in said whole blood.

23. The method of claim 1, wherein said returning comprises regulating a flow rate of said whole blood to the patient.

24. A system, comprising:

(a) an ultrafiltrate generator operative to separate ultrafiltrate from cellular components of blood;

(b) a blood control unit comprising;

a first pump operative to circulate blood from a patient, through said ultrafiltrate generator, and back to the patient; and

a second pump operative to draw said ultrafiltrate from said blood through said ultrafiltrate generator; and

(c) a recirculation circuit operative to treat said ultrafiltrate independently of said cellular components.

25. The system of claim 24, wherein said blood control unit further comprises a leak detector operative to analyze the composition of said ultrafiltrate downstream of said ultrafiltrate generator.

26. The system of claim 24, wherein said blood pump is operative to circulate said blood at a predetermined flow rate.

27. The system of claim 24, wherein said ultrafiltrate generator comprises a hollow fiber filter cartridge.

28. The system of claim 27, wherein said hollow fiber filter cartridge comprises a semi-permeable membrane having a predetermined molecular weight cut-off.

29. The system of claim 28, wherein said semi-permeable membrane has a predetermined molecular weight cut-off of about 100,000 Daltons.

30. The system of claim 28, wherein said semi-permeable membrane has a pore size of approximately 0.2 μ

m.

31. The system of claim 28, wherein said semi-permeable membrane has a pore size of approximately 0.1 μ

m.

32. The system of claim 27, wherein said hollow fiber filter cartridge comprises synthetic fibers.

33. The system of claim 32, wherein said synthetic fibers are polysulfone.

34. The system of claim 24, further comprising an anticoagulant infusion pump operative to infuse said blood with an anticoagulation agent.

35. The system of claim 34, wherein said anticoagulation agent is heparin.

36. The system of claim 24, further comprising a glucose pump operative to infuse said ultrafiltrate with glucose.

37. The system of claim 24, wherein said recirculation circuit comprises an oxygenator operative to oxygenate said ultrafiltrate.

38. The system of claim 24, wherein said recirculation circuit comprises a heating chamber operative to maintain said ultrafiltrate at a predetermined temperature.

39. The system of claim 24, wherein said recirculation circuit comprises a heat exchanger operative to maintain said ultrafiltrate at a predetermined temperature.

40. The system of claim 24, wherein said recirculation circuit is configured and operative to maintain said ultrafiltrate at approximately 37°

C.

41. The system of claim 24, wherein said recirculation circuit comprises an active cartridge containing active cells operative to effectuate a treatment of said ultrafiltrate.

42. The system of claim 41, further comprising a promoter infusion pump operative to infuse said ultrafiltrate with a promoter selected to enhance the activity of said active cells.

43. The system of claim 41, wherein said active cells are a subclone of the human hepatoblastoma cell line.

44. The system of claim 43, wherein said active cells are the C3A cell line.

45. The system of claim 41, wherein said recirculation circuit comprises a recirculation pump operative to circulate said ultrafiltrate through said active cartridge at a selected flow rate.

46. The system of claim 45, wherein said selected flow rate maintained by said recirculation pump differs from a flow rate maintained by said first pump in said blood control unit.

47. The system of claim 24, further comprising a conduit junction operative to recombine said ultrafiltrate with said blood prior to returning said blood to the patient.

48. The system of claim 47, further comprising a filter operative to filter said ultrafiltrate upstream of said conduit junction.

49. The system of claim 48, wherein said filter comprises a hollow fiber filter.

50. The system of claim 48, wherein said filter comprises one or more of a charcoal filter, an ammonia trap, and a mechanical filter.

51. The system of claim 24, further comprising:

a detector operative to detect gaseous contaminants in said blood; and

a mechanical filtration device operative to remove said gaseous contaminants from said blood.

52. The system of claim 41, wherein said recirculation circuit further comprises a blood gas analyzer operative to monitor said treatment.

53. An extracorporeal detoxification system, comprising:

(a) a blood circuit coupled to a patient and operative to communicate blood from the patient, through an ultrafiltrate generator, and back to the patient;

(b) a recirculation circuit coupled to said ultrafiltrate generator and operative to draw ultrafiltrate from said ultrafiltrate generator and to treat said ultrafiltrate independently of cellular components of said blood; and

(c) a conduit junction operative to recombine said ultrafiltrate in said recirculation circuit and said cellular components in said blood circuit prior to reintroduction to the patient.

54. The system of claim 53, wherein said recirculation circuit comprises a leak detector operative to analyze the composition of said ultrafiltrate downstream of said ultrafiltrate generator.

55. The system of claim 53, wherein said blood circuit comprises a blood pump operative to communicate said blood at a predetermined flow rate.

56. The system of claim 53, wherein said ultrafiltrate generator comprises a hollow fiber filter cartridge.

57. The system of claim 56, wherein said hollow fiber filter cartridge comprises a semi-permeable membrane having a predetermined molecular weight cut-off.

58. The system of claim 57, wherein said semi-permeable membrane allows albumin to permeate.

59. The system of claim 57, wherein said semi-permeable membrane does not allow a majority of fibrinogen to permeate.

60. The system of claim 56, wherein said hollow fiber filter cartridge comprises synthetic fibers.

61. The system of claim 60, wherein said synthetic fibers are polysulfone.

62. The system of claim 53, further comprising an anticoagulant infusion pump operative to infuse said blood with an anticoagulation agent.

63. The system of claim 62, wherein said anticoagulation agent is heparin.

64. The system of claim 53, further comprising a glucose pump operative to infuse said ultrafiltrate with glucose.

65. The system of claim 53, wherein said recirculation circuit comprises an oxygenator operative to oxygenate said ultrafiltrate.

66. The system of claim 53, wherein said recirculation circuit comprises a heating chamber operative to maintain said ultrafiltrate at a predetermined temperature.

67. The system of claim 53, wherein said recirculation circuit comprises a heat exchanger operative to maintain said ultrafiltrate at a predetermined temperature.

68. The system of claim 53, wherein said recirculation circuit comprises an active cartridge containing active cells operative to effectuate a treatment of said ultrafiltrate.

69. The system of claim 68, further comprising a promoter infusion pump operative to infuse said ultrafiltrate with a promoter selected to enhance the activity of said active cells.

70. The system of claim 68, wherein said active cells are a subclone of the human hepatoblastoma cell line.

71. The system of claim 70, wherein said active cells are the C3A cell line.

72. The system of claim 68, wherein said recirculation circuit comprises a recirculation pump operative to circulate said ultrafiltrate through said active cartridge at a selected flow rate.

73. The system of claim 72, wherein said selected flow rate maintained by said recirculation pump differs from a flow rate maintained in said blood circuit.

74. The system of claim 53, further comprising a filter operative to filter said ultrafiltrate upstream of said conduit junction.

75. The system of claim 74, wherein said filter comprises a hollow fiber filter.

76. The system of claim 74, wherein said filter comprises one or more of a charcoal filter, an ammonia trap, and a mechanical filter.

77. The system of claim 53, further comprising:

a detector operative to detect gaseous contaminants in said blood; and

a mechanical filtration device operative to remove said gaseous contaminants from said blood circuit.

78. The system of claim 68, wherein said recirculation circuit further comprises a blood gas analyzer operative to monitor said treatment.