ANTITHROMBOGENIC HOLLOW FIBER MEMBRANES AND FILTERS

• US 20110009799A1
• Filed: 07/12/2010
• Published: 01/13/2011
• Est. Priority Date: 05/15/2009
• Status: Active Grant

• Current Assignee: Interface Biologics, Inc.
• Original Assignee: Interface Biologics, Inc.
• Inventors: Esfand, Roseita, Mullick, Sanjoy, Chen, Hanje, Chang, Weilun, Steedman, Mark
• Granted Patent: US 8,877,062 B2
• Time in Patent Office: Days
• US Class Current: 604/6.14
• CPC Class Codes: A61L 33/062 Mixtures of macromolecular compounds
• CPC Class Codes: A61M 1/3672 Means preventing coagulation
• CPC Class Codes: A61M 1/3673 Anticoagulant coating, e.g. Heparin coating
• CPC Class Codes: A61M 2202/0413 Blood
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: B01D 2323/30 Cross-linking
• CPC Class Codes: B01D 2323/36 Introduction of specific chemical groups
• CPC Class Codes: B01D 63/022 Encapsulating hollow fibres
• CPC Class Codes: B01D 63/023 Encapsulating materials
• CPC Class Codes: B01D 67/0093 Chemical modification
• CPC Class Codes: B01D 69/02 characterised by their properties
• CPC Class Codes: B01D 69/08 Hollow fibre membranes manufacture of hollow fibres D01D5/24, D01F1/08
• CPC Class Codes: B01D 69/087 Details relating to the spinning process
• CPC Class Codes: B01D 69/0871 Fibre guidance after spinning through the manufacturing apparatus
• CPC Class Codes: B01D 71/44 Polymers obtained by reactions only involving carbon-to-carbon unsaturated bonds, not provided for in a single one of groups B01D71/26-B01D71/42
• CPC Class Codes: B01D 71/441 Polyvinylpyrrolidone
• CPC Class Codes: B01D 71/68 Polysulfones; Polyethersulfones
• CPC Class Codes: B29C 48/00 Extrusion moulding, i.e. expressing the moulding material through a die or nozzle which imparts the desired form; Apparatus therefor extrusion blow-moulding B29C49/04
• CPC Class Codes: B29C 48/05 Filamentary, e.g. strands
• CPC Class Codes: B29C 48/10 flexible, e.g. blown foils
• CPC Class Codes: B29L 2023/00 : Tubular articles B29L2024/00 takes precedence ; catheters B29L2031/7542
• CPC Class Codes: B29L 2031/731 : Filamentary material, i.e. comprised of a single element, e.g. filaments, strands, threads, fibres cables B29L2031/707

Abstract

The invention relates to extracorporeal blood circuits, and components thereof (e.g., hollow fiber membranes, potted bundles, and blood tubing), including 0.005% to 10% (w/w) surface modifying macromolecule. The extracorporeal blood circuits have an antithrombogenic surface and can be used in hemofiltration, hemodialysis, hemodiafiltration, hemoconcentration, blood oxygenation, and related uses.

Claims

1. An extracorporeal blood circuit comprising a polymeric component, wherein said polymeric component comprises a base polymer admixed with from 0.005% to 10% (w/w) of a surface modifying macromolecule, wherein said polymeric component has a surface positioned to contact blood when said extracorporeal blood circuit is in use, and wherein said surface is antithrombogenic when contacted with said blood.

2. The extracorporeal blood circuit of claim 1, wherein the thrombi deposition at said surface is reduced by at least 10% when contacted with blood, wherein said extracorporeal blood circuit has an increased average functional working life of at least 125%, or wherein said extracorporeal blood circuit reduces adverse advents in a subject receiving blood passing through said extracorporeal blood circuit.

10. The extracorporeal blood circuit of claim 1, wherein said extracorporeal blood circuit comprises a hollow fiber membrane of claim 3.

16. The extracorporeal blood circuit of claim 1, wherein said blood circuit comprises a potted bundle of claim 11.

20. The extracorporeal blood circuit of claim 1, wherein said extracorporeal blood circuit comprises a blood tubing of claim 18.

26. A method for treating a subject, said method comprising withdrawing blood from, and returning blood to, said subject via an extracorporeal blood circuit of claim 1, during which said subject receives less than a standard dose of anticoagulant, receives no anticoagulant, or wherein the adverse events experienced by said subject are reduced.

3. A hollow fiber membrane, said hollow fiber membrane comprising a base polymer admixed with from 0.005% to 10% (w/w) surface modifying macromolecule, wherein said hollow fiber membrane is antithrombogenic when contacted with blood.

4. The hollow fiber membrane of claim 3, wherein the thrombi deposition on said surface said hollow fiber membrane is reduced by at least 10% when contacted with blood, wherein said hollow fiber membrane has an operating pressure after 4 hours of use that is reduced by at least 10%, or wherein said hollow fiber membrane reduces adverse advents in a subject receiving blood passing through said hollow fiber membrane.

5. The hollow fiber membrane of claim 3, wherein said base polymer is selected from the group consisting of a polysulfone, a polyacrylonitrile, a cellulose acetate, a cellulose di- or tri-acetate, a polyimide, a poly(methyl methacrylate), a polycarbonate, a polyamide, a polypropylene, and a polyethylene.

6. The hollow fiber membrane of claim 5, wherein said base polymer is a polysulfone selected poly(oxy-1,4-phenylene sulfonyl-1,4-phenyleneoxy-1,4-phenyleneisopropylidene-1,4-phenylene) or polyether sulfone.

7. The hollow fiber membrane of claim 3, further comprising a hydrophilic pore forming agent.

8. The hollow fiber membrane of claim 7, wherein said hydrophilic pore forming agent is selected from polyvinylpyrrolidone, ethylene glycol, alcohols, polypropylene glycol, and polyethylene glycol, or mixtures thereof.

9. The hollow fiber membrane of claim 7, comprising from 80% to 96.5% (w/w) of said base polymer, from 3% to 20% (w/w) of said hydrophilic pore forming agent, and 0.005% to 10% (w/w) of said surface modifying macromolecule.

35. The hollow fiber membrane of claim 3, wherein said surface modifying macromolecule is selected from VII-a, VIII-a, VIII-b, VIII-c, VIII-d, IX-a, X-a, X-b, XI-a, XI-b, XII-a, XII-b, XIII-a, XIII-b, XIII-c, XIII-d, XIV-a, and XIV-b.

11. A potted bundle of hollow fiber membranes within an encasement comprising:

(a) an array of hollow fiber membranes, said array of hollow fiber membranes having lumens, a first set of fiber ends, and a second set of fiber ends;

(b) said first set of fiber ends being potted in a potting resin which defines a first internal wall near a first end of the encasement; and

(c) said second set of fiber ends being potted in a potting resin which defines a second internal wall near a second end of the encasement,

wherein said lumens of said hollow fiber membranes provide a path for the flow of blood from said first internal wall to said second internal wall, and

wherein said potting resin comprises from 0.005% to 10% (w/w) surface modifying macromolecule.

12. The potted bundle of claim 11, wherein said bundle has a prolonged working life, wherein said bundle has an increased average functional working life of at least 125%, wherein the thrombi deposition on said potted bundle is reduced by at least 10% when contacted with blood, wherein said bundle has an operating pressure after 4 hours of use that is reduced by at least 10%, wherein said potting resin is antithrombogenic when contacted with blood, or wherein said potted bundle reduces adverse advents in a subject receiving blood passing through said potted bundle.

13. The potted bundle of claim 11, wherein said bundle of potted hollow fiber membranes within an encasement is part of a blood purification device.

14. The potted bundle of claim 13, wherein said blood purification device is a hemodialysis, hemodiafiltration, hemofiltration, hemoconcentration, or oxygenator device.

15. The potted bundle of claim 11, wherein said potting resin comprises a cross-linked polyurethane.

17. A dialysis filter comprising a hollow fiber membrane of claim 3 or a potted bundle of claim 11, wherein said filter has a prolonged working life.

21. A method for treating a subject suffering from impaired kidney function, said method comprising performing a procedure selected from hemodialysis, hemofiltration, hemoconcentration, or hemodiafiltration on said subject using a dialysis filter, wherein said filter comprises a hollow fiber membrane of claim 3 or a potted bundle of claim 11.

22. The method of claim 21, wherein during said procedure said subject receives less than a standard dose of anticoagulant, receives no anticoagulant.

23. The method of claim 21, wherein said filter has a prolonged working life, wherein said filter has an increased average functional working life of at least 125%, wherein the thrombi deposition on said filter is reduced by at least 10% when contacted with blood, wherein said filter has an operating pressure after 4 hours of use that is reduced by at least 10%, or wherein the adverse events experienced by said subject are reduced.

24. A method for treating a subject suffering from impaired cardiac function, said method comprising performing a surgery selected from a coronary artery bypass grafting and a cardiac valve replacement using an oxygenator device, wherein said oxygenator device comprises a hollow fiber membrane of claim 3 or a potted bundle of claim 11.

25. The method of claim 24, wherein during said surgery said subject receives less than a standard dose of anticoagulant, receives no anticoagulant, or wherein the adverse events experienced by said subject are reduced.

27. A method for purifying a protein in blood, a blood product, or a combination thereof, said method comprising dialyzing said blood, said blood product, or said combination thereof across a hollow fiber membrane of claim 3 or a potted bundle of claim 11.

34. A dialysis kit comprising (i) a hollow fiber membrane of claim 3, a potted bundle of claim 11, a dialysis filter of claim 24, and/or blood tubing of claim 18;

and (ii) instructions for performing dialysis on a subject receiving less than a standard dose of anticoagulant or no anticoagulant.

36. The potted bundle of claim 11, wherein said potting resin comprises a surface modifying macromolecule selected from VII-a, VIII-a, IX-a, XI-a, VIII-d, and XI-b.

18. A blood tubing comprising a base polymer admixed with from 0.005% to 10% (w/w) surface modifying macromolecule, wherein said blood tubing is antithrombogenic when contacted with blood.

19. The blood tubing of claim 18, wherein said base polymer comprises polyvinyl chloride.

37. The blood tubing of claim 18, wherein said surface modifying macromolecule is selected from VII-a, XIV-a, and XIV-b.

28. A spinning solution for preparing a hollow fiber membrane, said spinning solution comprising (i) from 57% to 87% (w/w) of an aprotic solvent;

(ii) from 10% to 25% (w/w) of base polymer;

(iii) from 0.005% to 8% (w/w) of surface modifying macromolecule; and

(iv) from 3% to 10% (w/w) of hydrophilic pore forming agent.

29. The spinning solution of claim 28, wherein said aprotic solvent is selected from dimethylformamide, dimethylsulfoxide, dimethylacetamide, N-methylpyrrolidone, and mixtures thereof.

30. The spinning solution of claim 29, wherein said aprotic solvent further comprises less than 25% (v/v) of a low boiling solvent selected from tetrahydrofuran, diethylether, methylethyl ketone, acetone, and mixtures thereof.

31. The spinning solution of claim 28, wherein said hydrophilic pore forming agent is polyvinylpyrrolidone.

32. A method for making a hollow fiber membrane comprising the steps of:

(a) preparing a homogeneous spinning solution of claim 28; and

(b) extruding said homogeneous spinning solution from an outer annular orifice of a tube-in-orifice spinneret into an aqueous solution to form said hollow fiber membrane.

33. A method of potting hollow fiber membranes comprising the steps of

(a) forming a bundle of hollow fiber membranes, said bundle of hollow fiber membranes having lumens, a first set of fiber ends, and a second set of fiber ends;

(b) placing said first set of fiber ends and said second set of fiber ends in an uncured potting liquid;

(c) curing said potting liquid to form a potting resin in which said hollow fiber membranes are potted;

(d) cutting said potting resin and fiber ends to form a first wall in which said first set of fiber ends is potted and a second wall in which said second set of fiber ends is potted; and

(e) heating said first wall and said second wall,

wherein said potting liquid comprises from 0.005% to 10% (w/w) surface modifying macromolecule.