Biological implants of semipermeable amphiphilic membranes

• US 6,200,589 B1
• Filed: 02/27/1998
• Issued: 03/13/2001
• Est. Priority Date: 09/13/1996
• Status: Expired due to Term

• Current Assignee: University of Akron
• Original Assignee: University of Akron
• Inventors: Shamlou, Shahram, Levy, Richard P., Kennedy, Joseph P.
• Primary Examiner(s): Kulkosky, Peter F.
• Application Number:
  US09/032,316
• Time in Patent Office: 1,110 Days
• Field of Search: 424/484, 424/501, 435/180
• US Class Current: 424/424
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 31/005 Ingredients of undetermined constitution or reaction products thereof
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: C08L 23/22 Copolymers of isobutene; Butyl rubber ; Homo- or copolymers of other iso-olefins
• CPC Class Codes: C08L 23/26 modified by chemical after-treatment
• CPC Class Codes: C08L 33/04 Homopolymers or copolymers of esters C08L43/04 takes precedence

Abstract

An implantable biological device including a semipermeable membrane formed into a geometric shape capable of encapsulating biological cells and capable of immunoisolating the biological cells upon introduction into the body, the semipermeable membrane including an amphiphilic copolymer network having hydrophobic segments and hydrophilic segments, wherein the hydrophobic segments include polyolefins terminated with radicals selected from the group consisting of acryloyl groups, methacryloyl groups and mixtures thereof and wherein the hydrophilic segments include polyacrylates. Also provided is a method of encapsulating and immunoisolating cells using the semipermeable membrane and method of treating ailments using the implantable biological device.

Claims

1. A semipermeable biological implant comprising:

a semipermeable polymeric network formed into a geometric shape having an inner volume, said implant having cells encapsulated within said inner volume and capable of immununoisolating said encapsulated cells when said inplant is implanted into a biological medium, said semipermeable polymer network comprising the polymerization product of acryloyl or methacryoyl capped polyisobutylene and mixtures thereof, wherein said polyisobutylene is formed by cationic polymerization, and a hydrophilic segment derived from an acrylate selected from the group consisting of formulas (II), (III) and (IV)

where R₂ is hydrogen or methyl, R₃ is an alkylene group having from about 2 to about 4 carbon atoms, and R₄ and R₅ may be the same or different and are selected from the group consisting of hydrogen and alkyl groups having from 1 to about 4 carbon atoms;

wherein the ratio of capped polyisobutylene to said hydrophilic segments is from about 50;

50 parts by weight to about 30;

70 parts by weight; and

wherein the polymeric network allows the passage of glucose and insulin and prevents the passage of molecules having a molecular weight of greater than 50,000 daltons.

3. The biological implant of claim 1 wherein the geometric shape is an elongated tube.

4. The biological implant of claim 3 wherein the length of said elongated tube is less than about 20 cm.

5. The biological implant of claim 4 wherein the length of said elongated tube is less than about 10 cm.

6. The biological implant of claim 5 wherein the length of said elongated tube is about 2 cm to about 5 cm.

7. The biological implant of claim 3 wherein the inner diameter of said elongated tube is less than about 3 mm.

8. The biological implant of claim 7 wherein the inner diameter of said elongated tube is less than about 2 mm.

9. The biological implant of claim 8 wherein the inner diameter of said elongated tube is less than about 1 mm.

10. The biological implant of claim 3 wherein the inner volume of said elongated tube is less than about 1 ml.

11. The biological implant of claim 9 wherein the inner volume of said elongated tube is less than about 0.5 ml.

12. The biological implant, as set forth in claim 1 wherein said cells include pancreatic islet cells.

13. The biological implant, as set forth in claim 1 wherein said amphiphilic copolymer network membrane does not allow the passage of molecules having a molecular weight of greater than about 100,000 daltons.

14. The biological implant, as set forth in claim 1 wherein said polyisobutylene is formed by cationic polymerization.

15. The biological implant, as set forth in claim 1 wherein said cells include pancreatic islet cells.

16. The biological implant, as set forth in claim 1 wherein said polyisobutylene is formed by cationic polymerization.

17. The biological implant, as set forth in claim 1 wherein said polyisobutylene has a molecular weight of about 4,500.

18. The biological implant, as set forth in claim 1 wherein said polyisobutylene has a molecular weight of about 10,000.

19. The biological implant, as set forth in claim 1 wherein said polyisobutylene is methacryloyl capped.

20. The biological implant, as set forth in claim 1 wherein said amphiphilic copolymer network comprises about 50 parts by weight of said polyisobutylene and about 50 parts by weight of said hydrophilic segment.

21. The biological implant, as set forth in claim 1 wherein said amphiphilic copolymer network comprises about 40 parts by weight of said polyisobutylene and about 60 parts by weight of said hydrophilic segment.

22. The biological implant, as set forth in claim 1 wherein said amphiphilic copolymer network comprises about 30 parts by weight of said polyisobutylene and about 70 parts by weight of said hydrophilic segment.

2. A method of encapsulating cells within the inner volume of a geometric shape and immunoisolating cells from a biological medium comprising the steps of:

forming a semipermeable amiphiphilic copolymer network by reacting acryloyl-capped or methacryoyl-capped polyisotbutyiene, wherein said polyisobutylene is prepared by cationic polymerization, with hydrophilic segments derived from an acrylate selected from the group consisting of formulas (II), (III) and (IV)

where R₂ is hydrogen or methyl, R₃ is ail alkylene group having from about 2 to about 4 carbon atoms, and R₄ and R₅ may be the same or different and are selected from the group consisting of hydrogen and alkyl groups having from 1 to about 4 carbon atoms;

wherein the ratio of capped polyisobutylene to said hydrophilic segments is from about 50;

50 parts by weight to about 30;

70 parts by weight; and

wherein the semipermeable copolymer network allows the passage of glucose and insulin, and where said membrane prevents the passage of molecules having a molecular weight of greater than 50,000 daltons;

forming the semipermeable copolymer network into a geometric shape having an inner volume;

placing cells within the inner volume of said geometric shape;

sealing said geometric shape containing said cells, thereby encapsulating said cells within the inner volume of said geometric shape; and

implanting said geometric shape having cells encapsulated therein into a biological medium.