Bioresponsive pharmacologically-active polymers and articles made therefrom

• US 5,798,115 A
• Filed: 02/13/1997
• Issued: 08/25/1998
• Est. Priority Date: 02/15/1996
• Status: Expired due to Term

• Current Assignee: Interface Biologics, Inc.
• Original Assignee: Marc W. Mittelman, Paul J. Santerre
• Inventors: Santerre, Paul J., Mittelman, Marc W.
• Primary Examiner(s): Kulkosky, Peter F.
• Application Number:
  US08/799,938
• Time in Patent Office: 558 Days
• Field of Search: 424/78.08, 424/78.27, 424/423
• US Class Current: 424/423
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• 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 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C08G 18/5024 containing primary and/or secondary amino groups
• CPC Class Codes: C08G 18/73 acyclic

Abstract

This invention relates to pharmacologically-active polymeric compounds; to substrates, such as implantable medical devices formed thereof or coated therewith; and to methods of using said compounds or said substrates for providing pharmacological agents released in response to in vivo activation at a desired location in a mammal. The polymeric material has a backbone comprising a pharmacologically-active fragment covalently linked through at least two functional groups within the backbone, wherein the backbone comprises, preferably, polyamide, polyurethane and/or polyurea linkages with, optionally, polyester, polycarbonate, polyether and/or polyvinyl linkages. The preferred pharmacological compounds are fluoroquinolines, particularly, ciprofloxacin. The pharmacologically-active compounds provide in vivo enhanced long term anti-inflammatory, anti-bacterial, anti-microbial and/or anti-fungal activity.

Claims

1. A bioresponsive, pharmacologically-active, polymeric material having a polystyrene equivalent molecular weight selected from 2,000-200,000 and a backbone comprising a pharmacologically-active fragment formed from a fluoroquinolone covalently linked through two functional groups selected from a polyamide, polyurea, polyurethane and polysulfonamide formed from two or isocyanate functional groups within said backbone.

2. A polymeric material as defined in claim 1 further comprising one or more polyester, and polyether linkages.

3. A polymeric material as defined in claim 2 wherein said polyester linkage is made from polycaprolactone-diol.

4. A polymeric material as defined in claim 2 wherein said polyether linkage is made from polyether-diamine.

5. A polymeric material as defined in any one of the preceding claims wherein said backbone comprises 1,6-diamidohexane--or 1,12-diamidododecane-polyurethane, - polyurea, polyamide or polysulphonamide linkages.

6. A polymeric material as defined in claim 1 wherein said phannacologically-active fragment provides biological activity selected from the group consisting of anti-inflammatory, anti-bacterial, anti-microbial and anti-fingal activity under in vivo biochemical action.

7. A polymeric material as defined in claim 1 wherein said fluoroquinolin is ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazine-quinolone-3-carboxylic acid).

8. A polymeric material as defined in claim 1 made by the reaction of a polyisocyanate, an oligomeric α

-ω

diol, diamine or amino-alcohol, and a covalently linkable pharmacologically-active compound.

9. A polymeric material as defined in claim 1 wherein said polyisocyanate is selected from hexamethylene diisocyanate and dodecyl-diisocyanate;

said oligomeric diol is polycaprolactone-diol; and

said pharmacologically-active compound is an antibacterial fluoroquinolone.

10. A polymeric material as defined in claim 9 made by (a) reacting said hexamethylene diisocyanate or dodecyl-diisocyanate with polycaprolactone-diol to form a prepolymer;

and (b) reacting said prepolymer with ciprofloxacin.

11. A solid substrate comprising in whole or in part a bioresponsive pharmacologically-active polymeric material as defined in claim 1.

12. A solid substrate wholly or partially coated with a bioresponsive pharmacologically-active polymeric material as defined in claim 1.

13. A substrate as defined in claim 11 from the group consisting of an access device, suture, film, patch and dental fibre.

14. A method of delivering a bioresponsive pharmacologically-active compound to a selected site in a mammal, said method comprising, locating or disposing a polymeric material as defined in claim 1, at or adjacent the locus of said site.

15. A method of delivering a bioresponsive pharmacologically-active compound to a selected site in a mammal, said method comprising, locating or disposing a substrate as defined in claim 11 at or adjacent the locus of said site.