Anticoagulant and thrombo-resistant hollow fiber membranes for in-vivo plasmapheresis and ultrafiltration

• US 7,572,374 B2
• Filed: 01/18/2006
• Issued: 08/11/2009
• Est. Priority Date: 04/13/2000
• Status: Expired due to Fees

• Current Assignee: Transvivo, Inc.
• Original Assignee: Transvivo, Inc.
• Inventors: Kearns, Jacob C., Peters, Harold W., Gorsuch, Reynolds G., Handley, Harold H. Jr.
• Primary Examiner(s): KIM, SUN U
• Application Number:
  US11/334,994
• Publication Number:
  US 20060124530A1
• Time in Patent Office: 1,301 Days
• Field of Search: 210/600, 210/634, 210/644, 210/645, 210/646, 210/650, 210/651, 210/195.2, 210/200, 210/203, 210/483, 210/488, 210/490, 210/491, 210/500.1, 210/500.21, 210/500.23, 210/500.24, 210/500.41, 210/503, 210/504, 210/505, 210/506, 210/508, 422/44, 604/4.01, 604/5.01, 604/6.04, 604/6.09, 604/27
• US Class Current: 210/500.23
• CPC Class Codes: A61M 1/1678 intracorporal peritoneal dialysis A61M1/28
• CPC Class Codes: A61M 1/34 Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
• CPC Class Codes: A61M 1/3403 Regulation parameters
• CPC Class Codes: A61M 2205/3331 Pressure; Flow
• CPC Class Codes: B01D 2325/022 Asymmetric membranes
• CPC Class Codes: B01D 67/0016 Coagulation
• CPC Class Codes: B01D 67/0088 Physical treatment with compounds, e.g. swelling, coating or impregnation
• CPC Class Codes: B01D 67/0093 Chemical modification
• CPC Class Codes: B01D 69/02 characterised by their properties
• CPC Class Codes: B01D 69/04 Tubular membranes
• CPC Class Codes: B01D 69/08 Hollow fibre membranes manufacture of hollow fibres D01D5/24, D01F1/08
• CPC Class Codes: B01D 69/12 Composite membranes; Ultra-thin membranes
• CPC Class Codes: B01D 69/141 Heterogeneous membranes, e.g. containing dispersed material; Mixed matrix membranes
• CPC Class Codes: B01D 71/68 Polysulfones; Polyethersulfones

Abstract

An in-vivo plasmapheresis or in-vivo ultrafiltration membrane comprises a plurality of elongated hollow microporous fibers each fiber having an outer wall, an inner wall and an interior lumen extending along the length thereof and defined by an inner wall surface, and wherein the fiber wall structure is a substantially continuous change in mass density from the outer wall to the inner wall and comprises a continuum of voids bounded by solid frames, the fiber wall having an asymmetrical pore size and asymmetrical mass density between said inner wall surface and the outer wall surface with a higher mass density adjacent to the outer wall and a lower mass density adjacent to said inner wall, and characterized by a nitric oxide donor composition capable of producing or releasing nitric oxide or inducing nitric oxide production or release in-vivo with a blood vessel, distributed on or in the fiber wall.

Claims

1. An in-vivo plasmapheresis or in-vivo ultrafiltration membrane comprising a plurality of elongated hollow microporous fibers each fiber having an outer wall, an inner wall and an interior lumen extending along the length thereof and defined by an inner wall surface, and wherein the fiber wall structure is a substantially continuous change in mass density from said outer wall to said inner wall and comprises a continuum of voids bounded by solid frames, said fiber wall having an asymmetrical pore size and asymmetrical mass density between said inner wall surface and the outer wall surface, said fiber wall having a higher mass density adjacent to the outer wall and a lower mass density adjacent to said inner wall, said fibers capable of separating blood plasma and toxins from whole blood within a blood vessel by passing the plasma and toxins through said fiber wall from the outer wall surface to the interior lumen, and a nitric oxide donor composition capable of generating or releasing nitric oxide or inducing nitric oxide production or release in-vivo within a blood vessel, distributed on or in said fiber wall.

2. A membrane of claim 1 wherein said nitric oxide donor composition is coated, embedded, impregnated, bonded, absorbed or immobilized on or in said fiber wall.

3. A membrane of claim 1 wherein said nitric oxide donor composition comprises a polymer composition having a nitric oxide donor coated, embedded, impregnated, bonded, absorbed or immobilized thereon.

4. A membrane of claim 2 wherein said microporous fibers comprise a primary polymer and wherein said nitric oxide donor composition comprises a secondary polymer having said nitric oxide donor coated, embedded, impregnated, bonded, absorbed, immobilized or otherwise distributed thereon or therein.

5. A membrane of claim 1 wherein said microporous fibers comprise a polysulfone.

6. A membrane of claim 1 wherein said microporous fibers comprise a polyethersulfone.

7. A membrane of claim 6 wherein said polyethersulfone is modified with polyethylene oxide and/or polyethylene glycol.

8. A membrane of claim 1 wherein said nitric oxide donor composition comprises a nitric oxide-releasing N₂O₂⁻

functional group.

9. A membrane of claim 4 wherein said nitric oxide donor composition comprises a nitric oxide-releasing N₂O₂⁻

functional group.

10. A membrane of claim 9 wherein said nitric oxide-releasing N₂O₂⁻

functional group is bonded to said fiber wall.

11. A membrane of claim 6 wherein said nitric oxide donor composition comprises a nitric oxide-releasing N₂O₂⁻

functional group.

12. A membrane of claim 11 wherein said nitric oxide-releasing N₂O₂⁻

functional group is bonded to said fiber wall.

13. A membrane of claim 5 wherein said nitric oxide donor composition comprises a second polymer having a nitric oxide donor coated, embedded, impregnated, bonded or immobilized thereon.

14. A membrane of claim 6 wherein said nitric oxide donor composition comprises a second polymer having a nitric oxide donor coated, embedded, impregnated, bonded or immobilized thereon.

15. A membrane of claim 1 wherein said nitric oxide donor comprises a diazeniumdiolate.

16. A membrane of claim 5 wherein said nitric oxide donor comprises a diazeniumdiolate.

17. A membrane of claim 6 wherein said nitric oxide donor comprises a diazeniumdiolate.

18. A membrane of claim 8 wherein said nitric oxide donor comprises a diazeniumdiolate.

19. A membrane of claim 10 wherein said nitric oxide donor comprises a diazeniumdiolate.

20. A membrane of claim 13 wherein said nitric oxide donor comprises a diazeniumdiolate.

21. A membrane of claim 14 wherein said nitric oxide donor comprises a diazeniumdiolate.

22. A membrane of claim 1 wherein said nitric oxide donor composition comprises a catalyst capable of reducing endogenous NO donors in blood within a blood vessel.

23. A membrane of claim 5 wherein said nitric oxide donor composition comprises a catalyst capable of reducing endogenous NO donors in blood within a blood vessel.

24. A membrane of claim 6 wherein said nitric oxide donor composition comprises a catalyst capable of reducing endogenous NO donors in blood within a blood vessel.

25. A membrane of claim 22 wherein said microporous fibers comprise a polysulfone or polyethersulfone and wherein nitric oxide donor composition comprises a second polymer different from said polysulfone or polyethersulfone having said catalyst distributed therein.

26. A member of claim 25 wherein said catalyst comprises a xanthine oxidase or biomimetic catalyst.

27. A membrane of claim 1 wherein the higher mass density fiber wall is characterized by pores having a smaller average nominal pore size as compared to the average nominal pore size in the lower mass density fiber wall.

28. A membrane of claim 1 wherein said lower mass density is characterized by a nominal average pore diameter of between about 1 μ

m and about 60 μ

m.

29. A membrane of claim 1 wherein said higher mass density is characterized by a nominal average pore diameter of between about 0.10 μ

m and about 1 μ

m.

30. A membrane of claim 1 wherein said higher mass density is characterized by a nominal average pore diameter of between about 0.003 μ

m and about 0.006 μ

m.

31. A membrane of claim 1 having a sieving coefficient cutoff between about 1×

10^∝

daltons and about 7×

10⁴ daltons.

32. A membrane of claim 1 wherein said fibers have an average elongation breaking force strength of at least about 0.3 lbs. and an average elongation of at least about 45%.

33. A filter device for carrying out in-vivo plasma separation comprising one or more elongated hollow tubes and a plurality of elongated hollow microporous fibers each fiber having an outer wall, an inner wall and an interior lumen extending along the length thereof and defined by an inner wall surface, the ends of each fiber secured to said one or more tubes whereby the interior lumen of each fiber communicates with the interior of the one or more tubes, and wherein the fiber wall structure is a substantially continuous change in mass density from said outer wall to said inner wall and comprises a continuum of voids bounded by solid frames, said fiber wall having an asymmetrical pore size and asymmetrical mass density between said inner wall surface and the outer wall surface said fiber wall having a higher mass density adjacent to the outer wall and a lower mass density adjacent to said inner wall, said fibers capable of separating blood plasma and toxins from whole blood within a blood vessel by passing the plasma and toxins through said fiber wall from the outer wall surface to the interior lumen, and a nitric oxide donor composition capable of generating or releasing nitric oxide or inducing nitric oxide production or release in-vivo within a blood vessel, distributed on or in said fiber wall.

34. A filter device of claim 33 wherein said nitric oxide donor composition is coated, embedded, impregnated, bonded, absorbed or immobilized on or in said fiber wall.

35. A filter device of claim 33 wherein said nitric oxide donor composition comprises a polymer composition having a nitric oxide donor coated, embedded, impregnated, bonded, absorbed or immobilized thereon.

36. A filter device of claim 34 wherein said microporous fibers comprise a primary polymer and wherein said nitric oxide donor composition comprises a secondary polymer having said nitric oxide donor coated, embedded, impregnated, bonded, absorbed, immobilized or otherwise distributed thereon or therein.

37. A filter device of claim 33 wherein said microporous fibers comprise a polysulfone.

38. A filter device of claim 33 wherein said microporous fibers comprise a polyethersulfone.

39. A filter device of claim 38 wherein said polyethersulfone is modified with polyethylene oxide and/or polyethylene glycol.