Antithrombogenic hollow fiber membranes and filters

• US 9,884,146 B2
• Filed: 09/19/2014
• Issued: 02/06/2018
• Est. Priority Date: 05/15/2009
• Status: Active Grant

• Current Assignee: Interface Biologics, Inc.
• Original Assignee: Interface Biologics, Inc.
• Inventors: Mullick, Sanjoy, Chang, Weilun, Chen, Hanje, Steedman, Mark A., Esfand, Roseita
• Primary Examiner(s): DRODGE, JOSEPH W
• Application Number:
  US14/491,324
• Publication Number:
  US 20150008179A1
• Time in Patent Office: 1,236 Days
• Field of Search: 21032161, 21032178, 21032179, 2103218, 21032187, 21032188, 21032189, 210645, 210646, 21050023, 21050024, 21050027, 21050036, 21050041, 21050042, 604 501, 604 601, 604 609, 604 19, 604266, 604403, 138140, 138145, 138146, 138178
• 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. A hollow fiber membrane, said hollow fiber membrane comprising a base polymer admixed with from 0.005% to 10% (w/w) of a surface modifying macromolecule, wherein said base polymer is a polysulfone or a polyacrylonitrile and wherein said surface modifying macromolecule has a structure according to:

(a1) formula (VII);

F_T-[B-(Oligo)]_n-B-F_T 

 

(VII),

wherein Oligo is a soft oligomeric segment including polypropylene oxide or polytetramethylene oxide and having a theoretical molecular weight of from 500 to 3,000 Daltons;

B is a hard segment formed from hexamethylene diisocyanate;

F_T is a polyfluoroorgano group; and

n is an integer from 1 to 10;

(a2) formula (VIII);

2. The hollow fiber membrane of claim 1, wherein the thrombi deposition on said surface of said hollow fiber membrane is reduced by at least 10% compared to a hollow fiber membrane not having said surface modifying macromolecule 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.

3. The hollow fiber membrane of claim 1, wherein said base polymer is a polysulfone.

4. The hollow fiber membrane of claim 3, wherein said polysulfone is poly(oxy-1,4-phenylene sulfonyl-1,4-phenyleneoxy-1,4-phenyleneisopropylidene-1,4-phenylene) or polyether sulfone.

5. The hollow fiber membrane of claim 1, further comprising a hydrophilic pore forming agent.

6. The hollow fiber membrane of claim 5, wherein said hydrophilic pore forming agent is selected from polyvinylpyrrolidone, ethylene glycol, alcohols, polypropylene glycol, and polyethylene glycol, or mixtures thereof.

7. The hollow fiber membrane of claim 5, 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.

8. The hollow fiber membrane of claim 1, wherein said surface modifying macromolecule has a structure according to formula (VII),

F_T-[B-(oligo)]_n-B-F_T 

 

(VII),

wherein

(i) Oligo is a soft oligomeric segment including polypropylene oxide or polytetramethylene oxide having a theoretical molecular weight of from 500 to 3,000 Daltons;

(ii) B is a hard segment formed from hexamethylene diisocyanate;

(iii) F_T is a polyfluoroorgano group; and

(iv) n is an integer from 1 to 10.

9. The hollow fiber membrane of claim 8, wherein n is an integer from 1 to 3.

10. The hollow fiber membrane of claim 8, wherein F_T is selected from the group consisting of CH_mF_(3-m)(CF₂)_rCH₂CH₂—

and CH_mF_(3-m)(CF₂)_s(CH₂CH₂O)_x—

, wherein m is 0, 1, 2, or 3;

r is an integer from 2 to 20;

s is an integer from 1 to 20; and

x is an integer from 1 to 10.

11. The hollow fiber membrane of claim 8, wherein said surface modifying macromolecule of formula (VII) has the structure VII-a:

12. The hollow fiber membrane of claim 1, wherein said surface modifying macromolecule has a structure according to formula (XI),

13. The hollow fiber membrane of claim 12, wherein F_T is selected from the group consisting of CH_mF_(3-m)(CF₂)_rCH₂CH₂—

and CH_mF_(3-m)(CF₂)_s(CH₂CH₂O)_x—

, wherein m is 0, 1, 2, or 3;

r is an integer from 2 to 20;

s is an integer from 1 to 20; and

x is an integer from 1 to 10.

14. The hollow fiber membrane of claim 12, wherein said surface modifying macromolecule of formula (XI) has the structure XI-a:

15. The hollow fiber membrane of claim 1, wherein said surface modifying macromolecule has a structure according to formula (VIII),

16. The hollow fiber membrane of claim 15, wherein F_T is selected from the group consisting of CH_mF_(3-m)(CF₂)_rCH₂CH₂—

and CH_mF_(3-m)(CF₂)_s(CH₂CH₂O)_x—

, wherein m is 0, 1, 2, or 3;

r is an integer from 2 to 20;

s is an integer from 1 to 20; and

x is an integer from 1 to 10.

17. The hollow fiber membrane of claim 15, wherein said surface modifying macromolecule of formula (VIII) has the structure VIII-a:

18. The hollow fiber membrane of claim 1, wherein said surface modifying macromolecule has a structure according to formula (IX),

F_T-[B-(oligo)]_n-B-F_T 

 

(IX),

wherein

(i) Oligo is a soft oligomeric segment including poly 2,2 dimethyl-1,3-propylcarbonate and having a theoretical molecular weight of from 500 to 3,000 Daltons;

(ii) B is a hard segment formed from 4,4′

-methylene bis(cyclohexyl isocyanate);

(iii) F_T is a polyfluoroorgano group; and

(iv) n is 0, 1, 2, or 3.

19. The hollow fiber membrane of claim 18, wherein F_T is selected from the group consisting of CH_mF_(3-m)(CF₂)_rCH₂CH₂—

and CH_mF_(3-m)(CF₂)_s(CH₂CH₂O)_x—

, wherein m is 0, 1, 2, or 3;

r is an integer from 2 to 20;

s is an integer from 1 to 20; and

x is an integer from 1 to 10.

20. The hollow fiber membrane of claim 18 wherein said surface modifying macromolecule of formula (IX) has the structure IX-a:

21. The hollow fiber membrane of claim 1, wherein said surface modifying macromolecule has a structure according to formula (IV),

F_T-[B-(oligo)]_n-B-F_T 

 

(IV)

wherein

(i) A is a soft segment including hydrogenated polybutadiene, poly (2,2 dimethyl-1,3-propylcarbonate), polybutadiene, poly (diethylene glycol)adipate, poly (hexamethylene carbonate), poly (ethylene-co-butylene), neopentyl glycol-ortho phthalic anhydride polyester, diethylene glycol-ortho phthalic anhydride polyester, 1,6-hexanediol-ortho phthalic anhydride polyester, or bisphenol A ethoxylate;

(ii) B is a hard segment including a urethane; and

(iii) F_T is a polyfluoroorgano group, and

(iv) n is an integer from 1 to 10.

22. The hollow fiber membrane of claim 21, wherein F_T is selected from the group consisting of CH_mF_(3-m)(CF₂)_rCH₂CH₂—

and CH_mF_(3-m)(CF₂)_s(CH₂CH₂O)_x—

, wherein m is 0, 1, 2, or 3;

r is an integer from 2 to 20;

s is an integer from 1 to 20; and

x is an integer from 1 to 10.