Method of using crosslinked polymer compositions in tissue treatment applications

• US 6,166,130 A
• Filed: 04/30/1999
• Issued: 12/26/2000
• Est. Priority Date: 12/18/1995
• Status: Expired due to Term

• Current Assignee: Angiodevice International GmbH
• Original Assignee: Cohesion Technologies Inc. (Angiotech Pharmaceuticals Incorporated)
• Inventors: Rhee, Woonza M., Berg, Richard A., DeLustro, Frank A.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US09/302,852
• Time in Patent Office: 606 Days
• Field of Search: 525/54.1, 525/419, 525/420, 525/425
• US Class Current: 525/54.1
• CPC Class Codes: A61L 2300/232 Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08B 37/0075 Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
• CPC Class Codes: C08G 65/329 with organic compounds
• CPC Class Codes: C08H 1/00 Macromolecular products derived from proteins food proteins A23; glue, gelatine C09H
• CPC Class Codes: C08H 1/06 derived from horn, hoofs, hair, skin or leather
• CPC Class Codes: C08L 5/16 Cyclodextrin; Derivatives thereof
• CPC Class Codes: C08L 71/00 Compositions of polyethers obtained by reactions forming an ether link in the main chain of polyacetals C08L59/00; of epoxy resins C08L63/00; of polythioether-ethers C08L81/02; of polyether-sulfones C08L81/06; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: Y10S 623/90 Stent for heart valve
• CPC Class Codes: Y10S 623/901 Method of manufacturing prosthetic device

Abstract

Crosslinked polymer compositions comprise a first synthetic polymer containing multiple nucleophilic groups covalently bound to a second synthetic polymer containing multiple electrophilic groups. The first synthetic polymer is preferably a synthetic polypeptide or a polyethylene glycol that has been modified to contain multiple nucleophilic groups, such as primary amino (--NH₂) or thiol (--SH) groups. The second synthetic polymer may be a hydrophilic or hydrophobic synthetic polymer which contains, or has been derivatized to contain, two or more electrophilic groups, such as succinimidyl groups. The compositions may further comprise other components, such as naturally occurring polysaccharides or proteins (such as glycosaminoglycans or collagen) and/or biologically active agents. Also disclosed are methods for using the crosslinked polymer compositions to effect adhesion between a first surface and a second surface; to effect tissue augmentation; to prevent the formation of surgical adhesions; and to coat a surface of a synthetic implant.

Claims

1. A method of forming a three dimensional synthetic polymer matrix on a first tissue surface, comprising the steps of:

(a) providing a first synthetic polymer containing m nucleophilic groups and a second synthetic polymer containing n electrophilic groups, wherein the electrophilic groups react with the nucleophilic groups to form covalent bonds therewith, wherein m and n are each greater than or equal to two, and wherein m+n is greater than or equal to five;

(b) contacting the first synthetic polymer and the second synthetic polymer to initiate crosslinking; and

(c) simultaneous with or subsequent to step (b), applying the first synthetic polymer and the second synthetic polymer to the first tissue surface; and

(d) allowing the first synthetic polymer and the second synthetic polymer to become crosslinked to one another to form a three dimensional matrix.

2. The method of claim 1, further comprising contacting the first tissue surface with a second surface after step (c) but before step (d) to effect adhesion between the first tissue surface and the second surface.

3. The method of claim 2, wherein the second surface is a native tissue surface.

4. The method of claim 2, wherein the surface is a non-native tissue surface.

5. The method of claim 4, wherein the non-native tissue surface is a synthetic implant.

6. The method of claim 5, wherein the synthetic implant is selected from the group consisting of:

a donor cornea, an artificial blood vessel, a heart valve, an artificial organ, a bond prosthesis, an implantable lenticule, a vascular graft, a stent or a stent/graft combination.

7. The method of claim 1, wherein the first synthetic polymer and the second synthetic polymer are delivered from separate syringes and mixed together using syringe-to-syringe mixing prior to being applied to the first tissue surface.

8. The method of claim 1, wherein the first synthetic polymer and the second synthetic polymer are applied from separate chambers of a spray can or bottle with a spraying device and mixed at the first tissue surface.

9. The method of claim 1, wherein the first tissue surface is on or in a hard tissue or a soft tissue.

10. The method of claim 1, wherein the first tissue surface comprises, surrounds or is adjacent to a surgical site, and wherein the method further comprises the step of closing the surgical site.

11. The method of claim 1, wherein the mixture further comprises a protein or a polysaccharide.

12. The method of claim 1, wherein the mixture further comprises collagen.

13. The method of claim 1, wherein the mixture further comprises a biologically active agent.