Implants coated with collagen-polymer conjugates

• US 5,543,441 A
• Filed: 04/24/1995
• Issued: 08/06/1996
• Est. Priority Date: 11/21/1988
• Status: Expired due to Term

• Current Assignee: Angiotech Pharmaceuticals Incorporated
• Original Assignee: Collagen Corp. (Abbvie Incorporated)
• Inventors: Wallace, Donald G., Bentz, Hanne, DeLustro, Frank, Michaels, Alan S., Rhee, Woonza, Fries, Louis, Burns, Ramon A. Jr.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US08/427,576
• Time in Patent Office: 470 Days
• Field of Search: 604/891.1, 523/105, 525/937
• US Class Current: 523/105
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/426 Immunomodulating agents, i.e. cytokines, interleukins, interferons
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 24/102 Collagen
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/16 for reconstruction of eye parts, e.g. intraocular lens, cornea
• 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 27/44 having a macromolecular matrix
• 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 31/125 having a macromolecular matrix
• CPC Class Codes: C08H 1/06 derived from horn, hoofs, hair, skin or leather
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: C09J 189/06 : derived from leather or skin
• CPC Class Codes: Y10S 525/935 : Matrix admixed with synthetic fiber
• CPC Class Codes: Y10S 525/937 : Utility as body contact e.g. implant, contact lens or I.U.D.
• CPC Class Codes: Y10S 530/84 : Bones; tendons; teeth; cartilage

Abstract

Collagen, particularly atelopeptide collagen, exhibits improved handling characteristics when chemically conjugated and/or crosslinked with a synthetic hydrophilic polymer.

Claims

1. An implant exhibiting reduced immunogenicity and tissue irritation in an animal host, comprising:

a solid implant, coated with a composition comprising collagen crosslinked with a synthetic hydrophilic polymer.

2. The implant of claim 1 wherein said polymer comprises polyethylene glycol having a weight average molecular weight of about 400 to about 20,000.

3. The coated implant of claim 1, wherein all outer surfaces of the implant are coated with the coating.

4. The coated implant of claim 1, wherein the synthetic hydrophilic polymer is a difunctionally activated polyethylene glycol wherein each of the terminal hydroxy groups of said polyethylene glycol have been functionally activated to yield reactive groups capable of forming a covalent bond with an available lysine of said collagen.

5. The coated implant of claim 4, wherein the polymer is difunctional polyethylene glycol succinimidyl.

6. The coated implant of claim 1, wherein the coating further comprises:

a therapeutically effective amount of a cytokine of growth factor, wherein said cytokine of growth factor is chemically bound to said collagen by a covalent bond.

7. The coated implant of claim 6, wherein said cytokine or growth factor is selected from the group consisting of osteogenic factor, epidermal growth factor, transforming growth factor-α

, transforming growth factor-β

, transforming growth factor-dβ

2, platelet-derived growth factor-AA, platelet-derived growth factor-AB, platelet-derived growth factor-BB, acidic fibroblast growth factor, basic fibroblast growth factor, connective tissue activating peptide, β

-thromboglobulin, insulin-like growth factors, tumor necrosis factor, interleukins, colony stimulating factors, erythropoietin, nerve growth factor, and interferons.

8. The coated implant of claim 7, wherein said growth factor is selected from the group consisting of osteogenic factor extract, transforming growth factor-β

, transforming growth factor-β

1, transforming growth factor-β

2, and erythropoietin.

9. The coated implant of claim 1, wherein the coating further comprises:

a suitable particulate material dispersed homogeneously in the coating, wherein said suitable particulate material is selected from the group consisting of fibrillar crosslinked collagen, gelatin beads, polytetrafluoroethylene beads, silicone rubber beads, hydrogel beads, silicon carbide beads, glass beads, calcium mineral particles, hydroxyapatite particles, tricalcium phosphate particles, and mixtures of hydroxyapatite and tricalcium phosphate particles.