Systems for premeating molecules of predetermined molecular weight range

• US 5,756,632 A
• Filed: 06/02/1995
• Issued: 05/26/1998
• 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: White, Kathleen A., Ward, Robert S.
• Primary Examiner(s): Seidleck, James J.
• Assistant Examiner(s): Truong, Duc
• Application Number:
  US08/460,701
• Time in Patent Office: 1,089 Days
• Field of Search: 528/28, 528/25, 528/10, 528/34, 210/500.21, 210/500.23, 525/453, 525/459, 525/460
• 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 71/381 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. An article comprising a hydrophilic gel with a water content of at least about 35% substantially enclosed within a membrane comprising a biocompatible, hydrophilic, segmented block polyurethane copolymer

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 amphipathic 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% 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. An article comprising a hydrophilic gel with a water content of at least about 35% substantially enclosed within a membrane comprising a biocompatible, hydrophilic, segmented block polyurethane copolymer having a number average molecular weight of about 5,000 to 150,000, said copolymer

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 amphipathic 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% 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.

3. An article as in claim 2 wherein said hydrophilic gel contains at least 90% water.

4. An article as in claim 3 in which said hydrophilic gel is a hydrogel selected from the group consisting of alginates, guar gums, gum tragacanths, locust bean gums, methocels, xanthan gums, polyethylene oxides, polypropylene oxides, dextrans, acrylates, methacrylates, polyvinyl alcohols, polyvinyl pyrrolidones, and mixtures thereof.

5. An article as in claim 2 in which said copolymer has a number average molecular weight of about 5,000 to 150,000, and comprises

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;

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.

6. An article as in claim 2 in which said copolymer has a number average molecular weight of about 5,000 to 150,000, and comprises

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.

7. 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 a non-porous, semi-permeable, biocompatible film comprising a biocompatible, hydrophilic, segmented block polyurethane copolymer having a number average molecular weight of about 5,000 to 150,000, said copolymer

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% 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.

8. The method of claim 7 wherein the molecules that are permeated are selected from the group consisting of glucose, angiotensin I, glucagon, insulin, aprotinin, albumin, IgG, and oxygen.

9. The method of claim 7 wherein the film is in the form of hollow fibers.