ALPHA ADRENERGIC RECEPTOR AGONISTS FOR TREATMENT OF DEGENERATIVE DISC DISEASE

• US 20090263461A1
• Filed: 04/08/2009
• Published: 10/22/2009
• Est. Priority Date: 04/18/2008
• Status: Active Grant

• Current Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Original Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Inventors: MCKAY, William F.
• Granted Patent: US 9,072,727 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/4168 having a nitrogen attached in position 2, e.g. clonidine
• 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 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Effective treatments of pain and/or inflammation from degenerative disc disease and/or facet joint are provided. Through the administration of an effective amount of at least one alpha adrenergic agonist at or near a degenerative disc and/or facet joint, one can reduce, prevent or treat pain and/or inflammation caused by the degenerative disc disease and/or facet joint.

Claims

1. An implantable drug depot useful for reducing, preventing or treating pain and/or inflammation from a degenerative disc and/or facet joint in a patient in need of such treatment, the implantable drug depot comprising a therapeutically effective amount of an alpha adrenergic agonist, the drug depot being implantable at or near the degenerative disc and/or facet joint to reduce, prevent or treat pain and/or inflammation from the degenerative disc and/or facet joint, wherein the drug depot is capable of releasing an effective amount of the alpha adrenergic agonist over a period of at least one day.

2. An implantable drug depot according to claim 1, wherein the drug depot releases the alpha adrenergic agonist over a period of 3 days to 12 months and the degenerative disc comprises a disc herniation.

3. An implantable drug depot according to claim 1, wherein the alpha adrenergic agonist comprises an alpha-2 adrenergic agonist.

4. An implantable drug depot according to claim 3, wherein the alpha-2 adrenergic agonist comprises L-norepinephrine, clonidine, dexmetdetomidine, apraclonidine, tizanidine, brimonidine, xylometazoline, tetrahydrozoline, oxymetazoline, guanfacine, guanabenz, xylazine, moxonidine, medetomide, rilmenidine, UK 14,304, B-HT 933, B-HT 920, mivazerol, octopamine, tizanidine, or a combination thereof.

5. An implantable drug depot according to claim 1, wherein the drug depot comprises at least one biodegradable polymer comprising one or more of poly(lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide (PGA), D-lactide, D,L-lactide, L-lactide, D,L-lactide-co-ε

-caprolactone, D,L-lactide-co-glycolide-co-ε

-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 alpha adrenergic agonist at or near the degenerative disc over a period of up to 3 days and (ii) an effective amount of the alpha adrenergic agonist over a period of up to 12 months.

8. An implantable drug depot according to claim 1, wherein the drug depot releases about 20% to about 99% of the alpha adrenergic agonist relative to a total amount of the alpha adrenergic agonist loaded in the drug depot over a period of 3 days to 12 months after the drug depot is administered at or near the degenerative disc and/or facet joint.

9. An implantable drug depot according to claim 3, wherein the drug depot releases 0.1 mg to 100 mg of the alpha-2 adrenergic agonist over 24 to 48 hours for a period of at least 3 days to reduce, treat or prevent pain and inflammation from a degenerative disc and/or facet joint.

10. An implantable drug depot according to claim 4, wherein the drug depot comprises from about 5 wt. % to about 15 wt. % of clonidine and at least 80 wt. % of a biodegradable polymer based on the total weight of the drug depot and the drug depot is adapted to release an effective amount of the clonidine over a period of at least 150 days.

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

12. An implantable drug depot according to claim 4, wherein the drug depot is implanted within 5 cm of a disc herniation and the clonidine reduces pain and/or inflammation from the disc herniation.

13. A method of treating pain and/or inflammation from a degenerative disc and/or facet joint 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 alpha adrenergic agonist at or near the degenerative disc and/or facet joint, wherein the drug depot releases an effective amount of the alpha adrenergic agonist over a period of at least 1 day.

14. A method according to claim 13, wherein the alpha adrenergic agonist comprises an alpha-2 adrenergic agonist.

15. A method according to claim 13, wherein the drug depot releases 0.1 mg to 100 mg of the alpha adrenergic agonist over 24 to 48 hours for a period of at least 3 days to reduce, treat or prevent pain and inflammation.

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 alpha adrenergic agonist at or near the degenerative disc over a period up to 3 days to 14 days and (ii) an effective amount of the alpha adrenergic agonist over a period of up to 150 days.

19. A method of reducing pain and/or inflammation from a degenerative disc and/or facet joint in a patient in need of such treatment, the method comprising delivering one or more biodegradable drug depots comprising a therapeutically effective amount of an alpha-2 adrenergic agonist at or near the degenerative disc and/or facet joint of the patient, wherein the drug depot releases an effective amount of the alpha-2 adrenergic agonist over a period of at least 1 day.

20. An implantable drug depot useful for reducing, preventing or treating pain and/or inflammation from a degenerative disc and/or facet joint in a patient, the implantable drug depot comprising a therapeutically effective amount of alpha-2 adrenergic agonist and a polymer;

wherein the drug depot is implantable at or near the degenerative disc and/or facet joint to reduce, prevent or treat pain and/or inflammation, and the depot is capable of releasing (i) about 5% to about 20% of the alpha-2 adrenergic agonist relative to a total amount of the alpha-2 adrenergic agonist loaded in the drug depot over a first period of up to 72 hours and (ii) about 21% to about 99% of the alpha-2 adrenergic agonist relative to a total amount of the alpha-2 adrenergic agonist loaded in the drug depot over a subsequent period of up to 12 months.