Polymeric material that releases nitric oxide

• US 5,994,444 A
• Filed: 10/16/1997
• Issued: 11/30/1999
• Est. Priority Date: 10/16/1997
• Status: Expired due to Term

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Dror, Michael, Trescony, Paul, Rohly, Ken
• Primary Examiner(s): Michl, Paul R.
• Application Number:
  US08/951,910
• Time in Patent Office: 775 Days
• Field of Search: 525/428, 524/429
• US Class Current: 524/429
• CPC Class Codes: A61L 2300/114 Nitric oxide, i.e. NO
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/622 Microcapsules
• 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: 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: C08K 3/28 Nitrogen-containing compounds
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A polymeric material formed from a biodegradable polymer matrix is impregnated with a nitric oxide donor for continuous release of nitric oxide upon hydration.

Claims

1. A medical device comprising, prior to bio-degradation, a biodegradable or bioabsorbable non-acidic, non-reducing polymeric material comprising at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and copolymers thereof, the polymeric material having inorganic nitrite dispersed throughout at least portions of a matrix thereof, the polymeric material, in the presence of biological fluids, being capable of yielding at least one degradative product that facilitates the generation of nitric oxide from the inorganic nitrite, the degradative product serving as at least one of an acid and a reducing agent, the matrix being permeable to the nitric oxide generated therein.

3. The medical device of claim 1, wherein the polymeric material forms a coating, a film, a membrane, a matrix, or a combination thereof disposed on at least a portion of the medical device.

4. The medical device of claim 1, wherein the device is an implantable medical device selected from the group consisting of a pacemaker, an implantable pulse generator (IPG), an implantable cardiac defibrillator (ICD), a pacemaker cardioverter defibrillator(PCD), a defibrillator, a spinal stimulator, a brain stimulator, a sacral nerve stimulator, a stent, a catheter, a lead, an introducer, and a chemical sensor.

5. The medical device of claim 1, wherein the polymeric material comprises poly-L-lactic acid.

6. The medical device of claim 1, wherein the polymeric material comprises an acidic functionality or is capable of generating an acidic functionality.

7. The medical device of claim 6, wherein the polymeric material comprises a biocompatible, biodegradable polymer that biodegrades under physiological conditions to yield a product comprising an acidic functionality.

8. The medical device of claim 1, wherein the polymeric material comprises a reducing functionality or is capable of generating a reducing functionality.

9. The medical device of claim 8, wherein the polymeric material comprises a biocompatible, biodegradable polymer that biodegrades under physiological conditions to yield a product comprising a reducing functionality.

10. The medical device of claim 1, wherein the polymeric material comprises a biocompatible, biodegradable polymer that biodegrades under physiological conditions to yield a product comprising each of an acidic functionality and a reducing functionality.

11. The medical device of claim 1, wherein the inorganic nitrite is particulate in form.

12. The medical device of claim 1, wherein the inorganic nitrite is encapsulated within a plurality of microspheres.

13. The medical device of claim 1, wherein the inorganic nitrite comprises at least one of a monovalent inorganic cation selected from the group consisting of Na⁺, K⁺, and NH₄⁺.

14. The medical device of claim 1, wherein the inorganic nitrite comprises at least one of an organic cation selected from the group consisting of alkylammonium ion and pyridinium ion.

21. A method for releasing nitric oxide at an ex vivo site comprising positioning the polymeric material of claim 1 at the ex vivo site such that the polymeric material is disposed in an aqueous environment.

2. The medical device is a biocompatible polymer.

20. A method for therapeutic release of nitric oxide in vivo comprising positioning the polymeric material of claim 2 at a localized site in an aqueous environment in vivo.

15. A medical device comprising, prior to biodegradation, a biodegradable or bioabsorbable non-acidic, non-reducing polymeric material disposed on a blood-contacting surface thereof, the polymeric material comprising at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and copolymers thereof, the polymeric material having inorganic nitrite dispersed throughout at least portions of a matrix thereof, the polymeric material, in the presence of biological fluids, being capable of yielding at least one degradative product that facilitates the generation of nitric oxide from the inorganic nitrite, the degradative product serving as at least one of an acid and a reducing agent, the matrix being permeable to the nitric oxide generated therein.

16. The medical device of claim 15, wherein the polymeric material biodegrades under physiological conditions to yield a product comprising an acidic functionality, the inorganic nitrite comprising an acid-labile donor that releases nitric oxide in an acidic aqueous environment.

17. The medical device of claim 15, wherein the device is an implantable medical device selected from the group consisting of a pacemaker, an implantable pulse generator (IPG), an implantable cardiac defibrillator (ICD), a pacemaker cardioverter defibrillator(PCD), a defibrillator, a spinal stimulator, a brain stimulator, a sacral nerve stimulator, a stent, a catheter, a lead, an introducer, and a chemical sensor.

18. The medical device of claim 19, wherein the device is an implantable chemical gas sensor.

19. The medical device of claim 15, wherein the device is an extracorporeal device.

22. A method of making a medical device comprising, prior to bio-degradation, a biodegradable or bioabsorbable non-acidic, non-reducing polymeric material comprising at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and copolymers thereof, the polymeric material having inorganic nitrite dispersed throughout at least portions of a matrix thereof, the polymeric material, in the presence of biological fluids, being capable of yielding at least one degradative product that facilitates the generation of nitric oxide from the inorganic nitrite, the degradative product serving as at least one of an acid and a reducing agent, the matrix being permeable to the nitric oxide generated therein, the method comprising.

23. The method of claim 22, wherein the polymeric material comprises a biocompatible polymer matrix and the inorganic nitrite is in particulate form, the method further comprising providing the inorganic nitrite in particulate form.

24. The method of claim 22, further comprising sterilizing the polymeric material by subjecting the polymeric material to gamma radiation after dispersing the inorganic nitrite.

25. A medical device comprising, prior to bio-degradation, a biodegradable or bioabsorbable non-acidic, non-reducing biocompatible polymeric material comprising at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and copolymers thereof, the polymeric material having acid-labile inorganic nitrite dispersed throughout at least portions of a matrix thereof, the polymeric material, in the presence of acidic aqueous biological fluids, being capable of yielding at least one degradative product comprising an acidic functionality that facilitates the generation of nitric oxide from the inorganic nitrite, the matrix being permeable to the nitric oxide generated therein.

26. The medical device of claim 25, wherein the polymeric material forms a coating, a film, a membrane, a matrix, or a combination thereof disposed on at least a portion of the medical device.

27. The medical device of claim 25, wherein the device is an implantable medical device selected from the group consisting of a pacemaker, an implantable pulse generator (IPG), an implantable cardiac defibrillator (ICD), a pacemaker cardioverter defibrillator(PCD), a defibrillator, a spinal stimulator, a brain stimulator, a sacral nerve stimulator, a stent, a catheter, a lead, an introducer, and a chemical sensor.