Compositions and systems for forming crosslinked biomaterials and methods of preparation of use

• US 7,883,693 B2
• Filed: 01/31/2006
• Issued: 02/08/2011
• Est. Priority Date: 12/18/1995
• Status: Expired due to Fees

• Current Assignee: Angiodevice International GmbH (Angiotech Pharmaceuticals (US), Inc.)
• Original Assignee: Angiodevice International GmbH (Angiotech Pharmaceuticals (US), Inc.)
• Inventors: Trollsas, Olof Mikael, Sehl, Louis C., Toman, David, Wallace, Donald G., Schroeder, Jacqueline A., Chu, George H., DeLustro, Frank A.
• Primary Examiner(s): Hartley; Michael G
• Assistant Examiner(s): ROGERS, JAMES WILLIAM
• Application Number:
  US11/344,752
• Publication Number:
  US 20060210602A1
• Time in Patent Office: 1,834 Days
• Field of Search: None
• US Class Current: 424/78.03
• CPC Class Codes: A61F 2/0063 Implantable repair or support meshes, e.g. hernia meshes
• CPC Class Codes: A61L 17/145 Coating
• CPC Class Codes: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 24/08 Polysaccharides A61L24/043 takes precedence
• CPC Class Codes: A61L 24/102 Collagen
• CPC Class Codes: A61L 27/24 Collagen
• 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 31/044 Collagen
• CPC Class Codes: A61L 31/10 Macromolecular materials
• 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: C08F 283/00 Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
• CPC Class Codes: C08F 283/04 on to polycarbonamides, polyesteramides or polyimides C08F283/004 takes precedence
• CPC Class Codes: C08F 283/06 on to polyethers, polyoxymethylenes or polyacetals C08F283/004 takes precedence
• CPC Class Codes: C08G 2650/50 containing nitrogen, e.g. polyetheramines or Jeffamines(r)
• CPC Class Codes: C08G 65/329 with organic compounds
• CPC Class Codes: C08G 65/33306 : acyclic
• CPC Class Codes: C08G 65/33337 : cyclic
• CPC Class Codes: C08G 75/045 : from mercapto compounds and unsaturated compounds
• CPC Class Codes: C08G 75/26 : Polythioesters
• 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 2666/26 : Natural polymers, natural resins or derivatives thereof according to C08L1/00 - C08L5/00, C08L89/00, C08L93/00, C08L97/00 or C08L99/00
• CPC Class Codes: C08L 5/00 : Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
• CPC Class Codes: C08L 5/16 : Cyclodextrin; Derivatives thereof
• CPC Class Codes: C08L 51/003 : grafted on to macromolecular compounds obtained by reactions only involving unsaturated carbon-to-carbon bonds C08L51/04, C08L51/06 take precedence
• CPC Class Codes: C08L 53/00 : Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 67/06 : Unsaturated polyesters
• 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: C08L 81/02 : Polythioethers; Polythioether-ethers
• CPC Class Codes: C08L 89/06 : derived from leather or skin , e.g. gelatin
• CPC Class Codes: C08L 91/06 : Waxes
• CPC Class Codes: C09D 167/02 : Polyesters derived from dicarboxylic acids and dihydroxy compounds C09D167/06 takes precedence
• CPC Class Codes: C09J 151/003 : grafted on to macromolecular compounds obtained by reactions only involving unsaturated carbon-to-carbon bonds C09J151/04, C09J151/06 take precedence
• CPC Class Codes: C09J 153/00 : Adhesives based on block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Adhesives based on derivatives of such polymers
• CPC Class Codes: C09J 189/06 : derived from leather or skin

Abstract

Crosslinkable compositions are provided that readily crosslink in situ to provide biocompatible, nonimmunogenic crosslinked materials that may be used as adhesive compositions. The compositions comprise collagen and a plurality of crosslinkable components having reactive functional groups thereon, with the functional groups selected so as to enable inter-reaction between the components, i.e., crosslinking. Methods for preparing and using the compositions are also provided. Exemplary uses include tissue augmentation, biologically active agent delivery, bioadhesion, prevention of adhesions following surgery or injury, and coating of surgically acceptable patches and solid implants, the latter including sutures.

Claims

1. A composition for coating a surgically acceptable patch comprised of:

(a) a hydrophilic polymer;

(b) polyethylene glycol functionalized with m thiol groups, wherein m≧

2;

(c) polyethylene glycol functionalized with n succinimidyl groups, wherein n≧

2 and m+n≧

4; and

(d) a platelet derived growth factor,

wherein crosslinking of the composition upon contact with moisture results in a biocompatible, crosslinked matrix.

2. The composition of claim 1, wherein m+n>

4.

3. The composition of claim 1, wherein the surgically acceptable patch is selected from implantable surgical membranes and implantable surgical meshes.

4. The composition of claim 1, wherein the hydrophilic polymer is selected from synthetic polymers and naturally occurring polymers.

5. The composition of claim 4, wherein the naturally occurring hydrophilic polymer is selected from proteins, carboxylated polysaccharides, aminated polysaccharides, glycosaminoglycans, and activated polysaccharides.

6. The composition of claim 5, wherein the naturally occurring hydrophilic polymer is selected from nonfibrillar collagen, chemically modified collagen, fibrillar collagen, denatured collagen and combinations thereof.

7. The composition of claim 6, wherein the nonfibrillar collagen is selected from type IV collagen, type VI collagen, and type VII collagen.

8. The composition of claim 6, wherein the chemically modified collagen is methylated collagen.

9. The composition of claim 1, wherein the composition further comprises a third crosslinkable component C that is biocompatible and nonimmunogenic and has at least one functional group selected from

(a) nucleophilic groups capable of reacting with the succinimidyl groups and,

(b) electrophilic groups capable of reacting with the thiol groups,

wherein the total number of functional groups on component C is represented by p, such that m+n+p>

5.

12. The composition of claim 1 wherein m is 4 and n is 4.

10. A coated device comprising:

a surgically acceptable patche;

a coating composition on the surgically acceptable patch formed by crosslinking;

(a) polyethylene glycol functionalized with m thiol groups, wherein m≧

2;

(b) polyethylene glycol functionalized with n succinimidyl groups, wherein n≧

2 and m+n≧

4; and

(c) a platelet derived growth factor.

11. The device of claim 10 wherein the polyethylene glycol has a pentaerythritol core.

13. The device of claim 10 wherein m is 4 and n is 4.