Heparin entities and methods of use

• US 8,591,932 B2
• Filed: 09/17/2009
• Issued: 11/26/2013
• Est. Priority Date: 09/17/2009
• Status: Active Grant

• Current Assignee: W. L. Gore & Associates (W.L. Gore & Associates)
• Original Assignee: W. L. Gore & Associates (W.L. Gore & Associates)
• Inventors: Cleek, Robert L., Li, Mei, Drumheller, Paul D, Mardirosian, Nora
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US12/561,927
• Publication Number:
  US 20110064781A1
• Time in Patent Office: 1,531 Days
• Field of Search: None
• US Class Current: 424/423
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• 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: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: A61L 33/08 Polysaccharides
• CPC Class Codes: A61L 33/128 Other specific proteins or polypeptides not covered by A61L33/122 - A61L33/126
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 27/12 containing fluorine atoms

Abstract

The present invention relates to immobilized biologically active entities that retain a significant biological activity following manipulation. The invention also comprises a medical substrate comprising a heparin entity bound onto a substrate via at least one heparin molecule, wherein said bound heparin entity is heparinase-1 sensitive.

Claims

1. A medical substrate comprising:

a heparin entity bound onto a substrate via at least one heparin molecule, wherein said heparin entity comprises at least one heparin molecule and at least one core molecule, wherein said bound heparin entity is heparinase sensitive, and wherein said heparin molecule is bound to said substrate by one of;

an end point attachment, a loop attachment, an end point aldehyde attachment, and an aldehyde attachment along the length of said heparin molecule.

2. The medical substrate of claim 1, wherein said substrate is selected from the group consisting of polyethylene, polyurethane, silicone, polyamide-containing polymers, polypropylene, polytetrafluoroethylene, expanded-polytetrafluoroethylene and biocompatible metals.

3. The medical substrate of claim 2, wherein said substrate is expanded-polytetrafluoroethylene.

4. The medical substrate of claim 2, wherein said biocompatible metal is Nitinol.

5. The medical substrate of claim 1, wherein said substrate is a component of a medical device.

6. The medical substrate of claim 5, wherein said medical device is selected from the group consisting of grafts, vascular grafts, stents, stent-grafts, bifurcated grafts, bifurcated stents, bifurcated stent-grafts, patches, plugs, drug delivery devices, catheters, cardiac leads, balloons and indwelling filters.

7. The medical substrate of claim 6, wherein said stents can be used in cardiac, peripheral or neurological applications.

8. The medical substrate of claim 6, wherein said stent-grafts can be used in cardiac, peripheral or neurological applications.

9. The medical substrate of claim 1, wherein said core molecule is either cyclic, linear, branched, dendritic, Y, T, or star shaped.

10. The medical substrate of claim 1, wherein said core molecule is selected from the group consisting of proteins, hydrocarbons, aminoglycosides, polysaccharides and polymers.

11. The medical substrate of claim 10, wherein said protein is selected from the group consisting of albumin, colistin and polylysine.

12. The medical substrate of claim 10, wherein said polysaccharide is selected from the group consisting of cyclodextrin, cellulose, and chitosan.

13. The medical substrate of claim 10, wherein said polymer is selected from the group consisting of polyethylene glycol (PEG) and co-polymers tetrafluoroethylene.

14. The medical substrate of claim 1, wherein said heparin is derived from bovine or porcine sources.

15. The medical substrate of claim 1, wherein after heparinase treatment heparin or fragments thereof will not be detected on said substrate.

16. The medical substrate of claim 1, wherein after heparinase treatment heparin or fragments thereof will be detected at a significantly lower level than before heparinase treatment on said substrate.

17. The medical substrate of claim 15, wherein heparin or fragments thereof are detected by a label that binds to heparin or fragments thereof.

18. The medical substrate of claim 17, wherein said label that binds to heparin or fragments thereof is selected from the group consisting of dyes, polyclonal antibodies, and proteins.

19. The medical substrate of claim 18, wherein said dye is toluidine blue.

20. The medical substrate of claim 1, wherein after heparinase treatment an insignificant amount of toluidine blue will bind to residual heparin or fragments thereof but will not be visually detected on said substrate.

21. The medical substrate of claim 1, wherein after heparinase treatment an insignificant amount of toluidine blue will bind to residual heparin or fragments thereof, and wherein detector readings will be about background levels or be insignificantly different from background when compared to a substrate without heparin entities.