ANALGESIC AND ANTI-INFLAMMATORY COMPOSITIONS AND METHODS FOR REDUCING, PREVENTING OR TREATING PAIN AND INFLAMMATION

• US 20090263489A1
• Filed: 04/18/2008
• Published: 10/22/2009
• Est. Priority Date: 04/18/2008
• Status: Abandoned Application

• Current Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Original Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Inventors: ZANELLA, John
• Application Number:
  US12/105,474
• Publication Number:
  US 20090263489A1
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Effective treatments of acute pain and/or inflammation for extended periods of time are provided. Through the administration of an effective amount of sulfasalazine at or near a target site, one can relieve pain caused by diverse sources, including but not limited to spinal disc herniation (i.e. sciatica), spondilothesis, stenosis, discogenic back pain and joint pain as well as pain that is incidental to surgery. When appropriate formulations are provided within biodegradable polymers, this relief can be continued for at least three days. In some embodiments, the relief can be for at least twenty-five days, at least fifty days, at least one hundred days, at least one hundred and thirty-five days or at least one hundred and eighty days.

Claims

1. An implantable drug depot useful for reducing, preventing or treating pain and inflammation in a patient in need of such treatment, the implantable drug depot comprising a therapeutically effective amount of an analgesic and an anti-inflammatory agent or pharmaceutically acceptable salts thereof, the depot being implantable at a site beneath the skin to reduce, prevent or treat pain and inflammation, wherein the drug depot is capable of releasing an effective amount of the analgesic and an anti-inflammatory agent or pharmaceutically acceptable salts thereof over a period of at least 15 days to 6 months and the anti-inflammatory agent comprises clonidine, fluocinolone, dexamethasone, sulindac, sulfasalazine or a combination thereof.

2. An implantable drug depot according to claim 1, wherein the drug depot releases the analgesic and an anti-inflammatory over a period of 15 days to 150 days.

3. An implantable drug depot according to claim 1, wherein the analgesic comprises alfentanil, butorphanol, codeine, fentanyl, hydromorphone, levorphanol, meperidine, morphine, sufentanil, tramadol or a combination thereof.

5. An implantable drug depot according to claim 1, wherein the drug depot comprises a polymer and the polymer comprises poly (lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide (PLG), D-lactide, D,L-lactide, L-lactide, D,L-lactide-caprolactone, or D,L-lactide-glycolide-caprolactone or a combination thereof.

6. An implantable drug depot according to claim 1, wherein the drug depot comprises:

a polymer and the polymer comprises about 60% to 99% of the total weight % of the drug depot.

7. An implantable drug depot according to claim 1, wherein the drug depot releases (i) a bolus dose of the analgesic or pharmaceutically acceptable salt thereof at a site beneath the skin over a period of up to 3 days and (ii) an effective amount of the anti-inflammatory agent and the analgesic or pharmaceutically acceptable salt thereof over a period of 15 days up to 6 months.

8. An implantable drug depot according to claim 1, wherein the drug depot releases about 20% to about 99% of the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof relative to a total amount of the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof loaded in the drug depot over a period of 15 days to 6 months after the drug depot is administered to a target tissue site.

9. An implantable drug depot according to claim 1, wherein the drug depot releases 0.1 mg to 100 mg of the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof over 24 to 48 hours for a period of at least 15 days to reduce, treat or prevent pain and inflammation.

10. An implantable drug depot according to claim 1, wherein the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof are encapsulated in a plurality of depots comprising microparticles, microspheres, microcapsules, and/or microfibers suspended in a gel.

11. An implantable drug depot according to claim 1, wherein the drug depot is in the form of a pellet.

12. A method of making an implantable drug depot of claim 1, the method comprising combining a biocompatible polymer and a therapeutically effective amount of the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof and forming the implantable drug depot from the combination.

21. An implantable drug depot according to claim 5, wherein the polymer is polylactide.

23. An implantable drug depot according to claim 5, wherein the anti-inflammatory agent comprises fluocinolone, or dexamethasone or a combination thereof, and the polymer is polylactide.

4. (canceled)

13. A method of treating or preventing pain and inflammation in a patient in need of such treatment, the method comprising administering one or more biodegradable drug depots comprising a therapeutically effective amount of an analgesic and an anti-inflammatory agent or pharmaceutically acceptable salts thereof to a target tissue site beneath the skin, wherein the drug depot releases an effective amount of the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof over a period of at least 1 day.

14. A method according to claim 13, wherein the analgesic comprises alfentanil, butorphanol, codeine, fentanyl, hydromorphone, levorphanol, meperidine, morphine, sufentanil, tramadol or a combination thereof, and the anti-inflammatory agent comprises clonidine, fluocinolone, dexamethasone, sulindac, sulfasalazine or a combination thereof.

15. A method according to claim 13, wherein the drug depot releases 0.1 mg to 100 mg of the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof every 24 to 48 hours to reduce, treat or prevent pain and inflammation over a period of 3 days to 6 months after the drug depot is administered to the target tissue site.

16. A method according to claim 13, wherein the drug depot comprises a polymer comprising poly (lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide (PGA), D-lactide, D,L-lactide, L-lactide, D,L-lactide-caprolactone, D,L-lactide-glycolide-caprolactone or a combination thereof.

17. A method according to claim 13, wherein the drug depot comprises a polymer and the polymer comprises about 70% to about 90% of the total weight % of the drug depot.

18. A method according to claim 13, wherein the drug depot releases (i) a bolus dose of the analgesic or pharmaceutically acceptable salt thereof at a site beneath the skin over a period up to 3 days to 14 days and (ii) an effective amount of the anti-inflammatory agent or pharmaceutically acceptable salts thereof over a period of up to 150 days.

19. A method of reducing pain and inflammation in a patient in need of such treatment, the method comprising delivering one or more biodegradable drug depots comprising a therapeutic ally effective amount of an analgesic and an anti-inflammatory agent or pharmaceutically acceptable salts thereof to a target tissue site beneath the skin of the patient, wherein the drug depot releases an effective amount of the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof over a period of at least 1 day.

20. An implantable drug depot useful for reducing, preventing or treating pain and inflammation in a patient, the implantable drug depot comprising a therapeutically effective amount of an analgesic and an anti-inflammatory agent or pharmaceutically acceptable salts thereof and a polymer;

wherein the drug depot is implantable at a site beneath the skin to reduce, prevent or treat pain and inflammation, and the depot is capable of releasing (i) about 5% to about 20% of the analgesic or pharmaceutically acceptable salt thereof relative to a total amount of the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof loaded in the drug depot over a first period of up to 72 hours and (ii) about 21% to about 99% of the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof relative to a total amount of the analgesic and the anti-inflammatory agent or pharmaceutically acceptable salts thereof loaded in the drug depot over a subsequent period of 15 days to 6 months, wherein the anti-inflammatory agent comprises clonidine, fluocinolone, dexamethasone, sulindac, sulfasalazine or a combination thereof.

22. An implantable drug depot according to claim 20, wherein the polymer is polylactide.

24. An implantable drug depot according to claim 20, wherein the anti-inflammatory agent comprises fluocinolone, or dexamethasone or a combination thereof, and the polymer is polylactide.