IMPLANTABLE DEVICES FOR PRODUCING INSULIN

• US 20100209468A1
• Filed: 08/29/2007
• Published: 08/19/2010
• 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
• Granted Patent: US 8,361,489 B2
• Time in Patent Office: Days
• 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 substantially parallel 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 combination of the at least one spacing member, the first immunoisolatory membrane and the second immunoisolatory membrane yield an internal volume bounded by the spacing member, the first immunoisolatory membrane and the second immunoisolatory membrane where such internal volume is capable of receiving insulin producing cells suspended in an amphiphilic network.

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 first immunoisolatory membrane and the second immunoisolatory membrane are amphiphilic membranes having bi-continuous hydrophilic and hydrophobic domains and hydrophilic pore dimensions in the range of about 3.0 nm to about 4.0 nm.

7. The device of claim 1 wherein the first immunoisolatory membrane and the 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. The device of claim 1 wherein the first immunoisolatory membrane and the second immunoisolatory membrane are synthesized from hydrophilic poly(ethylene glycol) and hydrophobic polydimethylsiloxane, followed by crosslinking with tris(dimethylsilyloxy)phenylsilane.

9. The device of claim 1 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%.

10. The device of claim 1 wherein the amphiphilic network is prepared by free radical solution copolymerization of N,N-dimethyl acrylamide, 2-hydroxyethyl methacrylate, N-(dimethyl-amino)ethyl methacrylate and sulfoethylmethacrylate followed by methacrylate-telechelic polyisobutylenes.

11. The device of claim 1 wherein the amphiphilic membrane is comprised of polyethylene glycol and polydimethylsiloxane co-crosslinked by hydrosilation with at least one oxyphilic siloxane crosslinking agent.

12. The device of claim 1 wherein the amphiphilic membrane is comprised of polyethylene glycol and polydimethylsiloxane strands crosslinked by tris(dimethylsilyloxy)phenylsilane.

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

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

(ii) further hydrosilating the styryl-telechelic polyethylene glycol by vinyl-telechelic polydimethylsiloxane;

(iii) purifying the resulting diblock polymer of polyethylene glycol and polydimethylsiloxane separated by tris(dimethylsilyloxy)phenylsilane; and

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

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

implanting the device into a diabetic mammal; and

filling the internal volume with insulin producing cells suspended in an amphiphilic network.

15. The method of claim 14 wherein the device is implanted in subcutaneous loci.

16. The method of claim 14 wherein the device is implanted in intraperitoneal loci.

17. The method of claim 14 wherein the device is replenished with additional tissue cultures of insulin producing cells.

18. The method of claim 17 wherein the replenishment is via insertion of a hypodermic needle into one or more ports of the device.