초록 ▼

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 hemofi

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.

대표청구항 ▼

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

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):FT-[B-(Oligo)]n-B-FT  (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; FT 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; FT is a polyfluoroorgano group; and n is an integer from 0 to 10; (a3) formula (IX):FT-[B-(Oligo)]n-B-FT  (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); FT 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; FT is a polyfluoroorgano group; and n is an integer from 0 to 10; (a5) formula (IV),FT-[B-A]n-B-FT  (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; FT 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), FT-[B-(oligo)]n-B-FT  (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) FT 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 FT is selected from the group consisting of CHmF(3-m)(CF2)rCH2CH2— and CHmF(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: 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) FT is a polyfluoroorgano group; and(iv) n is 0, 1, 2, or 3. 13. The hollow fiber membrane of claim 12, wherein FT is selected from the group consisting of CHmF(3-m)(CF2)rCH2CH2— and CHmF(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: 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) FT is a polyfluoroorgano group; and(iv) n is 0, 1, 2, or 3. 16. The hollow fiber membrane of claim 15, wherein FT is selected from the group consisting of CHmF(3-m)(CF2)rCH2CH2— and CHmF(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: 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), FT-[B-(oligo)]n-B-FT  (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) FT is a polyfluoroorgano group; and(iv) n is 0, 1, 2, or 3. 19. The hollow fiber membrane of claim 18, wherein FT is selected from the group consisting of CHmF(3-m)(CF2)rCH2CH2— and CHmF(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: 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), FT-[B-(oligo)]n-B-FT  (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) FT is a polyfluoroorgano group, and(iv) n is an integer from 1 to 10. 22. The hollow fiber membrane of claim 21, wherein FT is selected from the group consisting of CHmF(3-m)(CF2)rCH2CH2— and CHmF(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.