Bupivacaine formulation in a polyorthoester carrier

• US 8,956,642 B2
• Filed: 04/17/2009
• Issued: 02/17/2015
• Est. Priority Date: 04/18/2008
• Status: Active Grant

• Current Assignee: Companion Spine LLC
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Hobot, Christopher M., Benz, Michael E., Hildebrand, Keith R., Pudil, Bryant J.
• Primary Examiner(s): Heyer, Dennis
• Assistant Examiner(s): PODGORSKI, DANIEL MICHAEL
• Application Number:
  US12/426,005
• Publication Number:
  US 20090202436A1
• Time in Patent Office: 2,132 Days
• Field of Search: None
• US Class Current: 424/426
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• 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 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61L 2300/402 Anaestetics, analgesics, e.g. lidocaine
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• 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 pain, such as chronic pelvic pain, for extended periods of time are provided. The treatments include the administration of one or more drug depots intraspinally wherein the drug depots include an effective amount of bupivacaine formulated within a polyorthoester. By administration of one or more drug depots, one can relieve pain caused by diverse sources, including but not limited to chronic pelvic pain syndromes, spinal disc herniation (i.e. sciatica), spondilothesis, stenosis, discongenic back pain and joint pain, as well as pain that is incidental to surgery. In some embodiments, the relief can be for at least thirty days, at least sixty days, at least one hundred days or at least one hundred and thirty-five days.

Claims

1. An implantable drug depot useful for reducing, or treating pain in a patient in need of such treatment, the drug depot comprising a polyorthoester and bupivacaine, the drug depot adapted to be administered intraspinally in the patient to reduce, or treat pain, wherein the drug depot is capable of releasing bupivacaine for a period of at least 30 days after administration, wherein the bupivacaine has a particle size range of about 5 microns to 50 microns, comprises a surface for burst release of the bupivacaine, has a modulus of elasticity in the range of about 2×

10⁴ to about 5×

10⁵ dynes/cm², and wherein the drug depot comprises mPEG.

2. An implantable drug depot according to claim 1, wherein the polyorthoester is capable of degrading in 200 days or less after the drug depot is administered at the site.

3. An implantable drug depot according to claim 1, wherein the bupivacaine is capable of being released for a period of 30 to 180 days after administration.

4. An implantable drug depot according to claim 1, wherein the bupivacaine is present in an amount of about 1 to about 50 wt. % of the drug depot and the polyorthoester is present in an amount of about 50 to about 99 wt. % of the drug depot.

5. An implantable drug depot according to claim 1, wherein the depot comprises microspheres.

6. An implantable drug depot according to claim 1, wherein the depot further comprises a radiographic marker.

7. An implantable drug depot according to claim 1, wherein the polyorthoester comprises at least 70 wt. % of the drug depot.

8. An implantable drug depot according to claim 1, further comprising one or more of polyaspirin, polyphosphazene, polyanhydride;

polyketal, collagen, starch, pre-gelatinized starch, hyaluronic acid, chitosan, gelatin, alginate, albumin, fibrin, vitamin E analog, d-alpha tocopheryl succinate, poly-ε

-caprolactone, dextran, polyvinylpyrrolidone, polyvinyl alcohol, PEGT-PBT copolymer, PEO-PPO-PEO, sucrose acetate isobutyrate, a different polyorthoester or a combination thereof.

9. An implantable drug depot according to claim 1, wherein the bupivacaine is in the form of a hydrochloride salt or a mixture of hydrochloride salt and free base.

10. An implantable drug depot according to claim 1, wherein the drug depot further comprises baclofen.

11. An implantable drug depot according to claim 1, wherein the drug depot has a diameter of 0.5 mm to 3 mm and a length of 50 mm to 100 mm.

12. An implantable drug depot according to claim 1, wherein the drug depot has a diameter of 3 mm and a length of 100 mm.

13. A method for treating pain, wherein the method comprises implanting a drug depot of claim 1 intraspinally in an organism, wherein the drug depot comprises bupivacaine in an amount from about 1 wt. % to about 50 wt. % of the drug depot.

14. A method according to claim 13, wherein the bupivacaine comprises from about 10 wt. % to about 40 wt. % of the drug depot.

15. A method according to claim 13, wherein the bupivacaine is released in an amount for a period of 30 to 135 days.

16. A method according to claim 13, wherein the drug depot is a ribbon.

17. A method according to claim 13, wherein the polyorthoester comprises at least 70 wt. % of the drug depot.

18. A method according to claim 13, wherein the depot is in the form of microspheres having an average diameter from about 1 micron to about 500 microns.

19. A method according to claim 13, wherein the bupivacaine is present in the depot in the form of particles, wherein at least 75% of the particles have a size from about 5 microns to about 50 microns in diameter.

20. A method according to claim 13, wherein the drug depot further comprises a radiographic maker.

21. A method of making an implantable drug depot of claim 1, the method comprising combining a polyorthoester and bupivacaine and forming the implantable drug depot from the combination.