Growth factor in connection with artificial implants

• US 5,386,012 A
• Filed: 01/12/1994
• Issued: 01/31/1995
• Est. Priority Date: 02/06/1990
• Status: Expired due to Fees

• Current Assignee: Lars Strid
• Original Assignee: Lars Strid
• Inventors: Strid, Lars
• Primary Examiner(s): Schain, Howard E.
• Assistant Examiner(s): Prickril, Benet
• Application Number:
  US08/180,497
• Time in Patent Office: 384 Days
• Field of Search: 530/331, 530/345, 525/54.1
• US Class Current: 530/331
• CPC Class Codes: A61K 38/06 Tripeptides
• CPC Class Codes: A61L 2300/102 Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence

Abstract

This invention utilizes the biological activity of the copper complex of the tripeptide glycyl-L-histidyl-L-lysine. This peptide is covalently bound to artificial implants where it has a chemoattractive effect and also acts when it is released by hydrolysis of the implants. The peptide increases fibroblastic collagen synthesis thereby enabling a more rapid replacement of the implants with human tissue.

Claims

1. An artificial implant material having the ability to increase natural collagen synthesis comprising a copper complex of the tripeptide glycyl-L-histidyl-L-lysine, which is bound to a biocompatible polymer through a covalent bond to the carboxyl group of the lysine.

2. The implant material of claim 1 wherein said copper complex is bound to said biocompatible polymer through a diamine compound.

3. The implant material of claim 2 wherein said polymer is formed from an α

-hydroxycarboxylic acid.

4. The implant material of claim 3 wherein said polymer is formed from an α

-hydroxycarboxylic acid selected form the group consisting of glycolic acid, lactic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid and mixtures thereof.

5. The implant material of claim 2 wherein a carboxyl group of said polymer forms a peptide bond with one amino-moiety of said diamine and the second amino-moiety of said diamine forms a peptide bond with the lysine moiety of said tripeptide-copper complex.

6. The implant material of claim 4 wherein said polymer is poly-L-lactic acid.

7. The implant material of claim 4 wherein said polymer is polyglycolic acid.

8. The implant material of claim 4 wherein said polymer is a copolymer of poly-L-lactic acid and polyglycolic acid.

9. The implant material of claim 5 wherein said implant material is poly-L-lactic acid.

10. The implant material of claim 5 wherein said implant material is polyglycolic acid.

11. The implant material of claim 5 wherein said implant material is a copolymer of poly-L-lactic acid and polyglycolic acid.

12. The implant material of claim 5 wherein said diamine is 1,6-hexanediamine.

13. The implant material of claim 2 wherein said biocompatible polymer is a polymer based on p-dioxanone having repeating units of the formula ##STR4## wherein R and R'"'"' are hydrogen, methyl or ethyl groups and n is a number between 15 and 700.

14. The implant material of claim 2 where said biocompatible polymer is a polymer based on p-dioxanone having repeating units of the formula ##STR5## where R and R'"'"' are hydrogen, methyl or ethyl groups.

15. An artificial implant material having the ability to increase natural collagen synthesis comprising:

a) copper (II) complex of the tripeptide glycyl-L-histidyl-L-lysine; and

b) a biocompatible polymer selected from the group consisting of polymers of polylactic acid, polyglycolic acid, and copolymers thereof wherein said tripeptide is bound to said polymer through a diamine of the formula NH₂ --(CH₂)_n --NH₂ wherein n is an integer from 2 to 6, and wherein one of the terminal amino groups of said diamine is bound to a free carbonyl group of said biocompatible polymer and the other terminal amino group of said diamine is bound to a free carbonyl group of the lysine of said copper (II) complex.

16. An artificial implants material according to claim 15, wherein said diamine is 1,6-hexanediamine.

17. An artificial implant material according to claim 16, wherein said biocompatible polymer is a polymer of poly-L-lactic acid.

18. An artificial implant material having the ability to increase natural collagen synthesis comprising a copper complex of the tripeptide glycyl-L-histidyl-L-lysine, wherein the C-terminal carboxyl group of said tripeptide is not involved in the copper complex and is covalently bound to a diamine compound through one amine moiety of said diamine, and the other amine moiety of said diamine is covalently bound to a biocompatible polymer.