PHOTOACTIVATED CROSSLINKING OF A PROTEIN OR PEPTIDE

• US 20110190813A1
• Filed: 08/14/2008
• Published: 08/04/2011
• Est. Priority Date: 08/14/2007
• Status: Active Grant

• Current Assignee: Cook Medical Incorporated (Cook Group Incorporated)
• Original Assignee: Cook Medical Incorporated (Cook Group Incorporated)
• Inventors: Ramshaw, John Alan Maurice, Elvin, Christopher Malcolm, Lindall, Charles Mark, Werkmeister, Jerome Anthony, Brownlee, Alan George
• Granted Patent: US 9,216,235 B2
• Time in Patent Office: Days
• US Class Current: 606/214
• CPC Class Codes: A61L 24/001 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 24/0026 Sprayable compositions
• CPC Class Codes: A61L 24/10 Polypeptides; Proteins A61L24/043 takes precedence
• CPC Class Codes: A61L 24/102 Collagen
• CPC Class Codes: A61L 24/106 Fibrin; Fibrinogen
• CPC Class Codes: A61L 24/108 Specific proteins or polypeptides not covered by groups A61L24/102 - A61L24/106
• CPC Class Codes: A61L 26/0028 Polypeptides; Proteins; Degradation products thereof
• CPC Class Codes: A61L 26/0061 Use of materials characterised by their function or physical properties
• CPC Class Codes: A61L 26/0076 Sprayable compositions
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: C08H 1/00 Macromolecular products derived from proteins food proteins A23; glue, gelatine C09H
• CPC Class Codes: C09J 189/00 Adhesives based on proteins; Adhesives based on derivatives thereof

Abstract

A method of crosslinking a protein or peptide for use as a biomaterial, the method comprising the step of irradiating a photoactivatable metal-ligand complex and an electron acceptor in the presence of the protein or peptide, thereby initiating a crosslinking reaction to form a 3-dimensional matrix of the biomaterial.

Claims

1. A method of crosslinking a protein or peptide for use as a biomaterial, the method comprising the step of irradiating a photoactivatable metal-ligand complex and an electron acceptor in the presence of the protein or peptide, thereby initiating a cross-linking reaction to form a 3-dimensional matrix of the biomaterial, wherein the protein is selected from the group consisting of a matrix protein, a protein that is at least partially denatured, and an endogenous protein.

3. The method as claimed in claim 1 wherein the matrix protein is selected from the group consisting of fibrinogen, fibrin, collagen, fibronectin, keratin and laminin, or admixtures thereof.

4. The method as claimed in claim 1 wherein the matrix protein is fibrinogen.

6. The method as claimed in claim 1 wherein denaturation of the protein occurs as a result of application of heat, physical or mechanical agitation or acid/alkali treatment or as a result of chemical modification.

7. The method as claimed in claim 1 wherein the denatured protein is gelatin.

8. The A method as claimed in claim 1 wherein the denatured protein is serum albumin in which the “

fast”

configuration has been induced.

10. The method as claimed in claim 1 wherein the endogenous protein is fibrin produced in situ by cleavage of fibrinogen.

11. The method as claimed in claim 1 wherein the electron acceptor is a peracid, a cobalt complex, a cerium (IV) complex or an organic acid.

12. The method as claimed in claim 11 wherein the electron acceptor is a persulfate, periodate, perbromate or perchlorate compound, vitamin B12, Co(III)(NH₃)₅Cl²⁺, cerium(IV)sulphate dehydrate, ammonium cerium(IV) nitrate, oxalic acid or EDTA.

13. The method as claimed in claim 12 wherein the electron acceptor is ammonium persulfate or sodium persulfate.

14. The method as claimed in claim 1 wherein the photoactivatable metal-ligand is an Ru(II), Pd(II), Cu(II), Ni(II), Mn(II) or Fe(III) complex.

15. The method as claimed in claim 14 wherein the complex is an Ru(II) bipyridyl complex, a Pd(II) porphyrin complex, a sulfonatophenyl Mn(II) complex or a Fe(III) protoporphyrin complex.

16. The method as claimed in claim 15 wherein the complex is a tris(bipyridyl) Ru(II) complex or hemin.

2. (canceled)

5. (canceled)

9. (canceled)

17-36. -36. (canceled)

37. A method of joining and/or sealing at least one substrate, comprising the steps of:

(1) applying a protein or peptide solution, a photoactivatable metal-ligand complex and an electron acceptor to at least one substrate;

(2) irradiating said material to photactivate the photoactivatable metal-ligand complex;

thereby initiating a cross-linking reaction to adhere or join said substrate to an adjacent substrate.

38. The method as claimed in claim 37 wherein the protein is a partially denatured protein.

39. The method as claimed in claim 38 wherein the protein is gelatin.

40. The method as claimed in claim 37 wherein the protein is a matrix protein.

41. A method of joining and/or sealing tissues in a surgical procedure or medical treatment, comprising the steps of:

(1) applying to a tissue portion a photoactivatable metal-ligand complex and an electron acceptor and optionally an at least partially denatured protein

(2) irradiating said tissue portion to photoactivate the photoactivatable metal-ligand complex;

thereby initiating a cross-linking reaction between (a) one or more endogenous proteins and/or

(b) said at least partially denatured protein

to seal said tissue portion or join said tissue portion to an adjacent tissue portion and

wherein said at least partially denatured protein has been rendered more susceptible to photochemical cross-linking compared to its native state

42. The method as claimed in claim 41 wherein thrombin is applied.

43-52. -52. (canceled)