Antithrombogenic hollow fiber membranes and filters

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):

wherein A is a soft oligomeric segment including polytetramethylene oxide and having a theoretical molecular weight of from 500 to 3,000 Daltons; B is a hard segment formed from hexamethylene diisocyanate biuret trimer; F T is a polyfluoroorgano group; and n is an integer from 0 to 10;

(a3) formula (IX):

F T -[B-(Oligo)] n -B-F T   (IX),

wherein 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; B is a hard segment formed from 4,4′-methylene bis(cyclohexyl isocyanate); F T is a polyfluoroorgano group; and n is an integer from 1 to 10; or

(a4) formula (XI):

wherein A is a soft segment comprising a block copolymer comprising polypropylene oxide and polydimethylsiloxane and having a theoretical molecular weight of from 1,000 to 5,000 Daltons; B is a hard segment formed from hexamethylene diisocyanate biuret trimer; F T is a polyfluoroorgano group; and n is an integer from 0 to 10;

(a5) formula (IV),

F T -[B-A] n -B-F T   (IV),

wherein 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; B is a hard segment including a urethane; F T is a polyfluoroorgano group, and n is an integer from 1 to 10.

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 m F (3-m) (CF 2 ) r CH 2 CH 2 — and CH m F (3-m) (CF 2 ) s (CH 2 CH 2 O) 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:

wherein n is an integer and the soft segment has a theoretical molecular weight of about 1000 Da.

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

wherein

(i) A is a soft segment comprising a block copolymer comprising polypropylene oxide and polydimethylsiloxane having a theoretical molecular weight of from 1,000 to 5,000 Daltons;

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

(iii) F T is a polyfluoroorgano group; and

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

13. The hollow fiber membrane of claim 12 , wherein F T is selected from the group consisting of CH m F (3-m) (CF 2 ) r CH 2 CH 2 — and CH m F (3-m) (CF 2 ) s (CH 2 CH 2 O) 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:

wherein m, n, and z are integers and the soft segment has a theoretical molecular weight of about 3000 Da.

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

wherein

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

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

(iii) F T is a polyfluoroorgano group; and

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

16. The hollow fiber membrane of claim 15 , wherein F T is selected from the group consisting of CH m F (3-m) (CF 2 ) r CH 2 CH 2 — and CH m F (3-m) (CF 2 ) s (CH 2 CH 2 O) 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:

wherein n is an integer and the soft segment has a theoretical molecular weight of about 1000 Da.

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 m F (3-m) (CF 2 ) r CH 2 CH 2 — and CH m F (3-m) (CF 2 ) s (CH 2 CH 2 O) 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:

wherein n is an integer and the soft segment has a theoretical molecular weight of about 1000 Da.

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 m F (3-m) (CF 2 ) r CH 2 CH 2 — and CH m F (3-m) (CF 2 ) s (CH 2 CH 2 O) 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.