Methods and compositions for treating post-operative pain comprising a local anesthetic
The present invention is directed to an implantable drug depot useful for reducing, preventing or treating post-operative pain in a patient in need of such treatment, the implantable drug depot comprising a polymer and a therapeutically effective amount of a local anesthetic or pharmaceutically acceptable salt thereof, wherein the drug depot is implantable at a site beneath the skin to reduce, prevent or treat post-operative pain, and the drug depot is capable of releasing (i) a bolus dose of the local anesthetic or pharmaceutically acceptable salt thereof at a site beneath the skin and (ii) a sustained release dose of an effective amount of the local anesthetic or pharmaceutically acceptable salt thereof over a period of at least 4 days.
1. An implantable drug depot useful for reducing, preventing or treating post-operative pain in a patient in need of such treatment, the implantable drug depot comprising a polymer comprising poly(D,L-lactide-co-glycolide), a therapeutically effective amount of a local anesthetic comprising bupivacaine or pharmaceutically acceptable salt thereof and an excipient comprising methoxy polyethylene glycol (mPEG), the depot being implantable at a site beneath the skin of the patient to reduce, prevent or treat post-operative pain, wherein the drug depot is capable of releasing (i) a bolus dose of the local anesthetic or pharmaceutically acceptable salt thereof at a site beneath the skin of the patient and (ii) a sustained release dose of an effective amount of the local anesthetic or pharmaceutically acceptable salt thereof over a period of at least 4 days, wherein the local anesthetic is present in an amount of about 60 wt. % of the depot, the polymer is present in an amount of about 30% of the depot and the methoxy polyethylene glycol (mPEG) is present in an amount of about 10 wt. % of the depot.
2. The implantable drug depot according to claim 1 , wherein the local anesthetic further comprises ropivacaine, mepivacaine, etidocaine, levobupivacaine, trimecaine, carticaine or articaine.
3. The implantable drug depot according to claim 1 , wherein the bupivacaine is in the form of a salt.
4. The implantable drug depot according to claim 1 , wherein the bupivacaine is in the form of a base.
5. The implantable drug depot according to claim 1 , wherein the polymer further comprises one or more of poly(lactide-co-glycolide), polylactide, polyglycolide, polyorthoester, D-lactide, D,L-lactide, poly(D,L-lactide), L-lactide, poly(D,L-lactide-co-caprolactone), poly(D,L-lactide-co-glycolide-co-caprolactone), polycaprolactone or a combination thereof.
6. The implantable drug depot according to claim 1 , wherein the polymer is capable of degrading in 30 days or less after the drug depot is implanted at the site.
7. The implantable drug depot according to claim 1 , wherein the drug depot is capable of releasing the local anesthetic in an amount between 50 and 800 mg per day for a period of 4 to 10 days.
8. A method of treating or preventing post-operative pain in a patient in need of such treatment, the method comprising administering one or more drug depots according to claim 1 to a target tissue before, during or after surgery, wherein the drug depot is capable of releasing an initial bolus dose of the local anesthetic or pharmaceutically acceptable salt thereof at a site beneath the skin of the patient followed by a sustained release dose of an effective amount of the local anesthetic or pharmaceutically acceptable salt thereof over a period of at least 4 days.
9. The method of treating or preventing post-operative pain according to claim 8 , wherein the local anesthetic further comprises ropivacaine, mepivacaine, etidocaine, levobupivacaine, trimecaine, carticaine or articaine.
10. The method of treating or preventing post-operative pain according to claim 8 , wherein the drug depot is capable of releasing about 40% to about 70% of the local anesthetic or pharmaceutically acceptable salt thereof relative to a total amount of the local anesthetic loaded in the drug depot over a period of 4 to 10 days after the drug depot is administered to the target tissue site.
11. The method of treating or preventing post-operative pain according to claim 8 , wherein the drug depot is capable of releasing between 50 and 800 mg/day of the local anesthetic or pharmaceutically acceptable salt thereof for a period of 4 to 10 days.
12. The method of treating or preventing post-operative pain according to claim 8 , wherein the polymer further comprises one or more of poly(lactide-co-glycolide), polylactide, polyglycolide, polyorthoester, D-lactide, D,L-lactide, poly(D,L-lactide), L-lactide, poly(D,L-lactide-co-caprolactone), poly(D,L-lactide-co-glycolide-co-caprolactone), polycaprolactone or a combination thereof.
13. An implantable drug depot useful for reducing, preventing or treating post-operative pain in a patient in need of such treatment, the implantable drug depot comprising a therapeutically effective amount of bupivacaine or pharmaceutically acceptable salt thereof, a polymer comprising poly(D,L-lactide-co-glycolide) and an excipient comprising methoxy polyethylene glycol (mPEG); wherein the depot is implantable at a site beneath the skin of the patient to reduce, prevent or treat post-operative pain, and the depot is capable of releasing (i) about 2% to about 50% of the bupivacaine or pharmaceutically acceptable salt thereof relative to a total amount of the bupivacaine or pharmaceutically acceptable salt thereof loaded in the drug depot over a first period of up to 48 hours and (ii) about 50% to about 98% of the bupivacaine or pharmaceutically acceptable salt thereof relative to a total amount of the bupivacaine or pharmaceutically acceptable salt thereof loaded in the drug depot over a subsequent period of up to 3 to 10 days, wherein the local anesthetic is present in an amount of about 60 wt. % of the depot, the polymer is present in an amount of about 30% of the depot and the methoxy polyethylene glycol (mPEG) is present in an amount of about 10 wt. % of the depot.
14. The implantable drug depot according to claim 13 , wherein the polymer further comprises one or more of poly(lactide-co-glycolide), polylactide, polyglycolide, polyorthoester, D-lactide, D,L-lactide, poly(D,L-lactide), L-lactide, poly(D,L-lactide-co-caprolactone), poly(D,L-lactide-co-glycolide-co-caprolactone), polycaprolactone or a combination thereof.
15. The implantable drug depot according to claim 13 , wherein the drug depot is capable of releasing between 50 and 800 mg/day of bupivacaine or pharmaceutically acceptable salt thereof.
16. The implantable drug depot according to claim 13 , wherein the polymer is capable of degrading in 30 days or less after the drug depot is implanted at the site.
17. A method of making an implantable drug depot of claim 13 , the method comprising combining a biocompatible polymer and a therapeutically effective amount of bupivacaine or pharmaceutically acceptable salt thereof and forming the implantable drug depot from the combination.