Coated transplants and method for making same

• US 4,696,286 A
• Filed: 05/22/1986
• Issued: 09/29/1987
• Est. Priority Date: 03/14/1985
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Cochrum, Kent C.
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): Smith, Jr., Jerome R.
• Application Number:
  US06/866,167
• Time in Patent Office: 495 Days
• Field of Search: 3/1, 128/1 R, 435/182, 435/1, 435/240, 435/241
• US Class Current: 435/1.1
• 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 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: C08L 77/04 Polyamides derived from alpha-amino carboxylic acids C08L77/10 takes precedence
• CPC Class Codes: Y10S 930/29 Polyamino acid or polypeptide with an uninterrupted series of peptide repeating units

Abstract

Transplants, such as pancreatic islets, are made suitable for transplantation into a genetically dissimilar individual by coating the transplant with a surface-conforming bonding bridge layer of a multifunctional material that binds chemically to a surface component of the transplant followed by a semipermeable, biologically compatible layer of a polymer that binds chemically to the bonding bridge layer.

Claims

1. A transplant suitable for transplantation into a genetically dissimilar individual, said transplant being coated with an immunological barrier membrane that conforms to the surface of the transplant,

said membrane comprising a noncytotoxic inner layer that is bonded chemically to the surface of the transplant, and an outer, biologically compatible, water-insoluble semipermeable layer bonded chemically to the inner layer, wherein the inner layer is comprised of a material selected from the group consisting of:

(a) aluminum hydroxide;

(b) a disaccharide;

(c) a polyfunctional cross-linking agent;

(d) an immunoglobulin to a surface component of the transplant;

(e) a lectin; and

(f) a polyionic polyamino acid having an opposite charge to that of the transplant surface; and

the outer layer is comprised of a polyamino acid that has reactive carboxyl, amino or imino side groups.

2. The transplant of claim 1 wherein said transplant is an endocrine transplant.

3. The transplant of claim 1 wherein said transplant is a pancreatic islet.

4. The transplant of claim 1 wherein the inner layer is comprised of a material selected from the group consisting of a bifunctional disulfide, an immunoglobulin that binds to a MHC antigen of the transplant, concanavalin A and polylysine.

5. The transplant of claim 1 wherein the polyamino acid of the outer layer is polylysine, polyarginine, polyaspartic acid, or polyglutamic acid.

6. The transplant of claim 5 wherein the molecular weight of the polyamino acid of the outer layer is in the range of 5,000 to 300,000 daltons and the thickness of the outer layer is between 0.1 and 10 microns.

7. The transplant of claim 3 wherein the inner layer is composed of aluminum hydroxide and the outer layer is composed of a first layer of polyaspartic acid chemically bound to the aluminum hydroxide and a second layer of polylysine chemically bound to the first layer.

8. The transplant of claim 1 wherein at least one intermediate layer of innocuous material is interposed between the inner and outer layers and the outer layer is bonded chemically to the contiguous intermediate layer.

9. A method of treating a transplant to make it suitable for transplantation into a genetically dissimilar individual comprising:

coating the transplant with a first or inner layer of a noncytotoxic material that forms a chemical bond with the surface of the transplant, said first layer conforming to the surface of the transplant, said first layer comprised of a material selected from the group consisting of

(a) aluminum hyhdroxide;

(b) a disaccharide;

(c) a polyfunctional cross-linking agent;

(d) an immunoglobulin to a surface component of the transplant;

(e) a lectin; and

(f) a polyionic polyamino acid having an opposite charge to that of the transplant surface; and

coating the transplant with a second or outer layer of a polymeric material that forms a chemical bond with the material of the first layer, said second layer being biologically compatible and semipermeable, said second layer comprising a polyamino acid that has reactive carboxyl, amino or imino side groups.

10. The method of claim 9 wherein said transplant is an endocrine transplant.

11. The method of claim 9 wherein said transplant is a pancreatic islet.

12. The method of claim 9 wherein the inner layer is comprised of a material selected from the group consisting of a bifunctional disulfide, an immunoglobulin that binds to a MHC antigen of the transplant, concanavalin A and polylysine.

13. The method of claim 9 wherein the polyamino acid of the outer layer is polylysine, polyarginine, polyaspartic acid, or polyglutamic acid.

14. The method of claim 13 wherein the molecular weight of the polyamino acid is in the range of 5,000 to 300,000 daltons and the thickness of the outer layer is between 0.1 and 10 microns.

15. The method of claim 11 wherein the inner layer is composed of aluminum hydroxide and the outer layer is composed of a first layer of polyaspartic acid chemically bound to the aluminum hydroxide and a second layer of polylysine chemically bound to the first layer.

16. The method of claim 9 wherein the transplant is coated with at least one intermediate layer of innocuous material interposed between the first layer and the second layer, with the second layer being bonded chemically to the contiguous intermediate layer.