Implantable devices for producing insulin

• US 8,361,489 B2
• Filed: 08/29/2007
• Issued: 01/29/2013
• Est. Priority Date: 08/29/2006
• Status: Active Grant

• Current Assignee: University of Akron
• Original Assignee: University of Akron
• Inventors: Kennedy, Joseph P., Erdodi, Gabor
• Primary Examiner(s): SINGH, ANOOP KUMAR
• Application Number:
  US12/439,057
• Publication Number:
  US 20100209468A1
• Time in Patent Office: 1,980 Days
• Field of Search: 424/422, 528/29, 528/31, 528/32, 604/891.1
• US Class Current: 424/422
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• 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 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

The present invention generally relates to implantable devices for producing insulin in diabetic animals. Some embodiments include amphiphilic biomembranes for use in biological applications (e.g., as an alternative and/or supplemental insulin source). Some embodiments also include live insulin-producing cells contained within one or more amphiphilic membranes so as to prevent or diminish an immuno-response and/or rejection by the host.

Claims

1. An implantable device for providing insulin comprising:

at least one spacing member having a suitable thickness, a first face, and a second face, wherein the first face and second face are positioned opposed to one another;

a first immunoisolatory membrane affixed to the first face of the at least one spacing member;

and a second immunoisolatory membrane affixed to the second face of the at least one spacing member;

wherein the first immunoisolatory membrane and second immunoisolatory membrane are amphiphilic membranes having pore dimensions in the range of about 3.0 nm to 4.0 nm, wherein the amphiphilic membranes are comprised of polyethylene glycol polymer and polydimethylsiloxane polymer strands crosslinked by bis(dimethylsilyloxy)ethoxydimethylsilyloxy phenylsilane to form an amphiphilic network, wherein the affixing of the first immunoisolatory membrane and the second immunoisolatory membrane to the at least one spacing member defines an internal volume bounded by the at least one spacing member, the first immunoisolatory membrane and the second immunoisolatory membrane, the internal volume holding insulin producing cells suspended in the amphiphilic network, wherein the amphiphilic network has a tensile strength in the range of about 0.5 MPa to about 3.0 MPa and an elongation in the range of about 50% to about 600%.

2. The device of claim 1, wherein the insulin producing cells are porcine endocrine cells.

3. The device of claim 1, wherein the distance between the first immunoisolatory membrane and the second immunoisolatory membrane is in the range of about 500 microns to about 700 microns.

4. The device of claim 1, wherein the spacing member contains one or more ports designed to permit filling and maintenance of the internal volume.

5. The device of claim 1, wherein the spacing member contains one or more vents.

6. The device of claim 1, wherein the amphiphilic membrane is prepared by:

(i) providing styryl-telechelic polyethylene glycol end-functionalized by hydrosilation with bis(dimethylsilyloxy)ethoxydimethylsilyloxy phenylsilane;

(ii) further hydrosilating the end functionalized styryl-telechelic polyethylene glycol by vinyl-telechelic polydimethylsiloxane to create a diblock polymer;

(iii) purifying the resulting diblock polymer; and

(iv) adding at least one acid to the purified diblock polymer.

7. The device of claim 1, wherein the first immunoisolatory membrane and second immunoisolatory membrane are amphiphilic water swollen membranes having bi-continuous hydrophilic pore dimensions in the range of about 3.0 nm to about 4.0 nm.

8. A method of using the device of claim 1, comprising the steps of:

implanting the device of claim 1 into a diabetic mammal; and

filling the internal volume of said device with insulin producing cells suspended in the amphiphilic network.

9. The method of claim 8, wherein the device is implanted in subcutaneous loci.

10. The method of claim 8, wherein the device is implanted in intraperitoneal loci.

11. A method of using the device of claim 7, comprising the steps of:

implanting the device of claim 7 into a diabetic mammal; and

filling the internal volume of said device with insulin producing cells suspended in the amphiphilic network.

12. The method of claim 11, wherein the device is implanted in subcutaneous loci.

13. The method of claim 11, wherein the device is implanted in intraperitoneal loci.

14. An implantable device for providing insulin comprising:

(i) cells for the production of insulin, and

(ii) an amphiphilic membrane that allows the for the passage of said insulin, wherein the amphiphilic membrane has pore dimensions in the range of about 3.0 nm to 4.0 nm, wherein the amphiphilic membranes are comprised of polyethylene glycol and polydimethylsiloxane polymer strands crosslinked by bis(dimethylsilyloxy) ethoxydimethylsilyloxy phenylsilane to form an amphiphilic network, wherein the amphiphilic network has a tensile strength in the range of about 0.5 MPa to about 3.0 MPa and an elongation in the range of about 50% to about 600%, and wherein the bis(dimethylsilyloxy) ethoxydimethylsilyloxy phenylsilane is a chain extender that also functions as a crosslinker.

15. The device of claim 14, wherein the insulin producing cells are porcine endocrine cells.

16. The device of claim 14, wherein the implantable device contains one or more vents.

17. The device of claim 14, where the amphiphilic membrane is produced by first preparing a functional multiblock polymer and then crosslinking the functional multiblock polymer.

18. The device of claim 17, where the functional multiblock polymer is produced by hydrosilation.

19. The device of claim 17, where the functional multiblock polymer is crosslinked by a condensation reaction.