Copolymers and non-porous, semi-permeable membrane thereof and its use for permeating molecules of predetermined molecular weight range

• US 5,428,123 A
• Filed: 04/23/1993
• Issued: 06/27/1995
• Est. Priority Date: 04/24/1992
• Status: Expired due to Term

• Current Assignee: Polymer Technology Group, Inc. (DSM-Firmenich AG)
• Original Assignee: Polymer Technology Group, Inc. (DSM-Firmenich AG)
• Inventors: Ward, Robert S., White, Kathleen A.
• Primary Examiner(s): Michl, Paul R.
• Assistant Examiner(s): Truong, Duc
• Application Number:
  US08/052,361
• Time in Patent Office: 795 Days
• Field of Search: 128/28, 128/25, 128/80, 128/34, 525/453, 525/459, 525/460, 210/500.21, 210/500.23
• US Class Current: 528/28
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 33/068 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L33/062 takes precedence
• CPC Class Codes: B01D 69/08 Hollow fibre membranes manufacture of hollow fibres D01D5/24, D01F1/08
• CPC Class Codes: B01D 71/38 Polyalkenylalcohols; Polyalkenylesters; Polyalkenylethers; Polyalkenylaldehydes; Polyalkenylketones; Polyalkenylacetals; Polyalkenylketals
• CPC Class Codes: B01D 71/381 Polyvinylalcohol
• CPC Class Codes: B01D 71/54 Polyureas; Polyurethanes
• CPC Class Codes: B01D 71/60 Polyamines
• CPC Class Codes: B01D 71/80 Block polymers
• CPC Class Codes: C07K 1/34 by filtration, ultrafiltration or reverse osmosis
• CPC Class Codes: C08G 18/12 using two or more compounds having active hydrogen in the first polymerisation step
• CPC Class Codes: C08G 18/283 Compounds containing ether groups, e.g. oxyalkylated monohydroxy compounds
• CPC Class Codes: C08G 18/2865 Compounds having only one primary or secondary amino group; Ammonia
• CPC Class Codes: C08G 18/2885 containing halogen atoms
• CPC Class Codes: C08G 18/289 containing silicon
• CPC Class Codes: C08G 18/3228 acyclic
• CPC Class Codes: C08G 18/44 Polycarbonates
• CPC Class Codes: C08G 18/4808 Mixtures of two or more polyetherdiols
• CPC Class Codes: C08G 18/4833 Polyethers containing oxyethylene units
• CPC Class Codes: C08G 18/4854 : Polyethers containing oxyalkylene groups having four carbon atoms in the alkylene group
• CPC Class Codes: C08G 18/6674 : with compounds of group C08G18/3203
• CPC Class Codes: C08G 18/6685 : with compounds of group C08G18/3225 or polyamines of C08G18/38
• CPC Class Codes: C08L 75/04 : Polyurethanes
• CPC Class Codes: C12N 11/093 : Polyurethanes

Abstract

A biocompatible, hydrophilic, segmented block polyurethane copolymer which comprises 5 to 45 wt % of a hard segment and 95 to 55 wt % of a soft segment selected from a hydrophilic, hydrophobic and amphipathic oligomer is disclosed. The copolymer is capable of forming a non-porous, semi-permeable film of a tensile strength greater than 300 and up to 10,000 psi, and has an ultimate elongation greater than 300% and up to 1,500% and a water absorption such that the sum of the volume fraction of absorbed water and the hydrophilic volume fraction of the soft segment exceeds about 100% and is up to about 2,000% of the dry polymer volume. The film is permeable to cell nutrients and waste molecules of up to about 6,000 to 600,000 molecular weight and is substantially impermeable to cells and particulate matter. A non-porous, semi-permeable, biocompatible film is formed from the block copolymer of the invention in the form of a flexible sheet or a hollow fiber. Also disclosed is a method of permeating molecules of a predetermined molecular weight range while preventing the passage of larger molecular weight molecules, cells, and condensed phases of matter between two fluids comprising interposing between the two fluids the non-porous film of the invention.

Claims

1. A biocompatible, hydrophilic, segmented block polyurethane copolymer having a number average molecular weight of about 5,000 to 150,000,

comprising about 5 to 45 wt % of at least one hard segment;

and

about 95 to 55 wt % of at least one soft segments comprising at least one hydrophilic, hydrophobic or amphipatic oligomer selected from the group consisting of aliphatic polyols, aliphatic and aromatic polyamines and mixtures thereof;

the copolymer being capable of forming a substantially non-porous semi-permeable film having a tensile strength greater than about 350 psi and up to about 10,000 psi, an ultimate elongation greater than about 300% and up to about 1,500 t and a water absorption such that the sum of the volume fraction of absorbed water and the hydrophilic volume fraction of the soft segment exceeds about 100% and up to about 2,000% of the dry polymer volume and exceeds about 50% and up to about 95% of the wet polymer volume and being permeable to monodisperse molecules of up to about 6,000 to 600,000 molecular weight and substantially impermeable to particulate matter.

2. The copolymer of claim 1, wherein the volume fraction of absorbed water is about 50% or greater than the total volume of the water swollen polymer.

3. The copolymer of claim 1, wherein the aliphatic polyols of the soft segment are selected from the group consisting of linear, branched and graft polyarylene, polyalylene and polyalkenyline oxides, random and block copolymers thereof, polycarbonate polyols, hydroxyl-terminated silicones, random and block copolymers thereof with polyalkylene oxides, linear and branched polyalkenyl, and polyalkylene polyols, and mixtures thereof.

4. The copolymer of claim 1, wherein the soft segment is selected from the group consisting of amine-terminated polyalkylene oxides and random, block and graft copolymers thereof, amine-terminated polydialkylsiloxanes, random and block copolymers thereof with polyalkylene oxides and mixtures thereof.

5. The copolymer of claim 1, further comprising an end group selected from the group consisting of monofunctional aliphatic polyols, aliphatic or aromatic amines and mixtures thereof.

6. The copolymer of claim 5, wherein

(a) the monofunctional aliphatic polyols of the end group are selected from the group consisting of monofunctional polyalkylene oxides, siloxanes and mixtures thereof;

and

(b) the monofunctional amines of the end group are selected from the group consisting of dialkylamines, amine functionalized siloxanes, amine terminated polyakylene oxides and mixtures thereof.

7. The copolymer of claim 1, wherein the soft segment is selected from the group consisting of reaction products of an organic diisocyanate with a polyamine and a polyol.

8. The copolymer of claim 7, wherein the organic diisocyanate of the hard segment is selected from the group consisting of alkyl diisocyanates, arylalkyldiisocyanates, alkyl-cycloalkyl diisocyanates, alkylaryl diisocyanates, cycloalkyl diisocyanates, aryl diisocyanates, and cycloalkylaryl diisocyanates, which may be further substituted with oxygen, and mixtures thereof.

9. The copolymer of claim 7, wherein the polyol of the hard segment is selected from the group consisting of alkylene, cycloalkylene and arylene diols, triols, tetraalcohols, pentaalcohols and mixtures thereof.

10. The copolymer of claim 7, wherein the polyamine of the hard segment is selected from the group consisting of alkyl, cycloalkyl, and aryl amines, which may be further substituted with N, O or halogen, complexes thereof with alkali metal salts, and mixtures thereof.

11. The copolymer of claim 1, wherein the soft segment comprises a polyethyleneoxide of molecular weight greater than about 3,000 daltons.

12. The copolymer of claim 11, wherein the polyethyleneoxide has a molecular weight of about 8,000 or greater.

13. The copolymer of claim 6, wherein the soft segment comprises a blend of polyols selected from the group consisting of a polyethyleneoxide of molecular weight greater than about 3,000 daltons, a polyethyleneoxide-polytetramethyleneoxide copolymer and a polyethyleneoxide homopolymer, a polyethyleneoxide-polytetramethyleneoxide copolymer and an ethyleneoxide-capped polyethyleneoxide copolymer, a polyethyleneoxide-polypropyleneoxide copolymer and a polyethyleneoxide homopolymer, a polyethyleneoxide-polypropyleneoxide copolymer and a polypropyleneoxide homopolymer, a polyethyleneoxide homoploymer and a polytetramethyleneoxide homopolymer, a polyethyleneoxide copolymer and a polycarbonate homopolymer, a polyethyleneoxide copolymer and a polybutadiene homolymer, and a polyethyleneoxide copolymer and a polyisobutylene homopolymer.

14. The copolymer of claim 13, wherein the soft segment comprises a blend of a polyethyleneoxide-polytetramethyleneoxide copolymer and polyethyleneoxide homopolymer.

15. The copolymer of claim 13, wherein the soft segment is a blend of a polyethyleneoxide-polytetramethyleneoxide copolymer and a polyethyleneoxide-polypropyleneoxide copolymer.

16. The copolymer of claim 13, wherein the soft segment is a blend of a polyethyleneoxide-polytetramethyleneoxide copolymer and an ethyleneoxide-capped polypropyleneoxide polymer.

17. The copolymer of claim 13, wherein the soft segment is a blend of a polyethyleneoxide-polypropyleneoxide copolymer and a polyethyleneoxide homopolymer.

18. The copolymer of claim 13, wherein the soft segment is a blend of a polyethyleneoxide-polypropyleneoxide copolymer and a polypropyleneoxide homopolymer.

19. The copolymer of claim 13, wherein the soft segment is a blend of a polyethyleneoxide homopolymer and a polytetramethyleneoxide homopolymer providing the copolymer having a lesser tensile strength and elongation in the wet state than in its dry state.

20. The copolymer of claim 13, wherein the soft segment is a blend of a polyethyleneoxide-containing copolymer and a polycarbonate homopolymer.

21. The copolymer of claim 13, wherein the soft segment is a blend of a polyethyleneoxide-containing copolymer and a polybutadiene homopolymer.

22. The copolymer of claim 13, wherein the soft segment is a blend of a polyethyleneoxide-containing copolymer and a polyisobutylene homopolymer.

23. A non-porous, semi-permeable, biocompatible film formed from the block copolymer of claim 1.

24. The non-porous film of claim 23, in the form of a flexible sheet or a hollow membrane.

25. The non-porous film of claim 23, being attached to a substrate.

26. The non-porous film of claim 25, in the form of a coating deposited onto a substrate.

27. The non-porous film of claim 26, wherein the substrate is a woven or knitted substrate or a porous polymer.

28. The non-porous film of claim 25, having a thickness of about 1 to 150 microns.

29. The non-porous film of claim 23, having a thickness of about 5 to 150 microns.

30. A method of permeating molecules of a predetermined molecular weight range while substantially preventing the passage of cells and particulate matter between two fluids comprising interposing between the two fluids the nonporous film of claim 23.

31. A biocompatible, hydrophilic, segmented or block polyurethane copolymer having a number average molecular weight of about 5,000 to 150,000, comprising

about 5 to 45% of at least one hard segment selected from the group consisting of reaction products of an organic diisocyanate and a polyamine and a polyol;

and

about 95 to 55 wt % of a hydrophilic soft segment comprising a blend of a polyethyleneoxide-polytetramethyleneoxide copolymer and a polyethyleneoxide homopolymer.

32. The block polyurethane copolymer of claim 31, wherein the organic dissocyanate comprises 4,4'"'"'-diphenylmethane diisocyanate.

33. The block polyurethane copolymer of claim 31, wherein the organic diisocyanate comprises hydrogenated diphenylmethane diisocyante.

34. The block polyurethane copolymer of claim 31, wherein the hard segment polyol comprises an alkylenediol.

35. The block polyurethane copolymer of claim 34, wherein the hard segment polyol comprises butanediol.

36. The block polyurethane copolymer of claim 31, wherein the hard segment polyamine comprises an alkylenediamine.

37. The block polyurethane copolymer of claim 36, wherein the hard segment polyamine comprises ethylenediamine.

38. A non-porous film made from the polymer of claim 31.

39. The film of claim 31, being attached to a substrate.

40. A biocompatible, hydrophilic, segmented or block polyurethane copolymer having a number average molecular weight of about 5,000 to 150,000, comprising

about 5 to 45 wt % of a least one hard segment selected from the group consisting of reaction products of an organic diisocyanate and a polyamine and a polyol;

and

about 95 to 55 wt % of a hydrophilic soft segment comprising a blend of polyethyleneoxide-polytetramethyleneoxide copolymer and a polyethyleneoxide-polypropylene oxide copolymer.

41. The block polyurethane copolymer of claim 40, wherein the organic diiisocyanate comprises 4,4'"'"'-diphenylmethane diisocyanate (MDI).

42. The block polyurethane copolymer of claim 40, wherein the organic diisocyanate comprises hydrogenated diphenylmethane diisocyanate (HMDI).

43. The block polyurethane copolymer of claim 40, wherein the hard segment polyol comprises an alkylenediol.

44. The block polyurethane copolymer of claim 43, wherein the hard segment polyol comprises butanediol.

45. The block polyurethane copolymer of claim 40, wherein the hard segment polyamine comprises an alkylenediamine.

46. The block polyurethane copolymer of claim 40, wherein

the hard segment polyamine is ethylene diamine.

47. A non-porous film made from the polymer of claim 40.

48. The non-porous film of claim 47, being attached to a substrate.

49. A biocompatible, hydrophilic, segmented or block polyurethane copolymer having a number average molecular weight of about 5,000 to 150,000, comprising

about 5 to 45 wt % of at least one hard segment selected from the group consisting of reaction products of an organic diisocyanate and a polyamine and a polyol;

and

about 95 to 55 wt % of a soft segment comprising a blend of a polyethyleneoxide-homopolymer and a polyethyleneoxide-polypropylene oxide copolymer.

50. The block polyurethane copolymer of claim 49, wherein the organic diisocyanate comprises 4,4'"'"'-diphenylmethane diisocyanate (MDI).

51. The block polyurethane copolymer of claim 49, wherein the organic diisocyanate comprises hydrogenated diphenylmethane diisocyanate (HMDI).

52. The block polyurethane copolymer of claim 49, wherein the hard segment polyol comprises an alkylenediol.

53. The block polyurethane copolymer of claim 52, wherein the hard segment polyol comprises butanediol.

54. The block polyurethane copolymer of claim 49, wherein the hard segment polyamine comprises an alkylenediamine.

55. The block polyurethane copolymer of claim 54, wherein the hard segment polyamine comprises ethylenediamine.

56. A nonporous film, made from the polymer of claim 49.

57. The non-porous film of claim 56, being attached to a substrate.