AN IMPLANTABLE DRUG DEPOT HAVING A REVERSIBLE PHASE TRANSITION MATERIAL FOR TREATMENT OF PAIN AND/OR INFLAMMATION
Effective treatments of pain and/or inflammation are provided that utilize a reversible phase transition material of a drug depot. When heat, cold or another suitable form of energy, e.g., ultrasound energy is applied to the reversible phase transition material, the release of an analgesic and/or anti-inflammatory agent from a drug depot is increased.
1 . An implantable drug depot useful for reducing, preventing or treating pain and/or inflammation in a patient in need of such treatment, the implantable drug depot being implantable at a site beneath the skin and comprising an effective amount of an analgesic muscle relaxant, and/or an anti-inflammatory agent disposed within a reversible phase transition material of the drug depot, wherein the reversible phase transition material is capable of releasing a bolus dose of the analgesic, muscle relaxant and/or the anti-inflammatory agent when heat, cold or other suitable energy form is applied to the skin of a patient to reduce, prevent or treat pain and/or inflammation.
2 . An implantable drug depot according to claim 1 , wherein the drug depot releases an effective amount of the analgesic, muscle relaxant and/or the anti-inflammatory agent to treat post operative pain over a period of 3 to 10 days.
3 . An implantable drug depot according to claim 1 , wherein the site beneath the skin comprises at least one dermis, connective tissue, adipose tissue, muscle, ligament, tendon, cartilage, spinal disc, spinal foraminal space near the spinal nerve root, facet or synovial joint, or spinal canal.
4 . An implantable drug depot according to claim 2 , wherein the pain or inflammation is associated with hernia repair, orthopedic or spine surgery or a combination thereof.
5 . An implantable drug depot according to claim 2 , wherein the post operative pain is from one or more surgical procedures comprising arthroscopic surgery, an excision of a mass, spinal fusion, thoracic, cervical, or lumbar surgery, pelvic surgery or a combination thereof.
6 . 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-ε-caprolactone, D,L-lactide-glycolide-ε-caprolactone, or a combination thereof and the reversible phase transition material comprises paraffin waxes, poloxamers, polylactones, poly(N-isopropylacrylamide) homopolymer, poly(N-isopropylacrylamide)acrylamide copolymer, copolymer of poly(N-isopropylacrylamide) containing silane monomers selected from [3-(methacryloyloxy)propyl]trimethoxysilane, [2-(methacryloyloxy)ethoxy]-trimethylsilane and methacryloyloxy)trimethylsilane, copolymer of poly(hydroxypropyl methacrylamide), dicarboxymethylaminopropyl methacrylamide, xyloglucan, ethyl(hydroxyethyl)cellulose, poly(ethyleneoxide-b-propylene oxide-b-ethylene oxide) and its copolymers, poly(ethylene oxide)/(D,L-lactic acid-co-glycolic acid)copolymers, combinations of chitosan and polyol salts, poly(silamine), and poly(organophosphazene) or a combination thereof.
7 . An implantable drug depot according to claim 1 , wherein the reversible phase transition polymer comprises at least one biodegradable polymer comprising paraffin waxes, poloxamers, polylactones, paraffin waxes, poly(N-isopropylacrylamide) homopolymer, poly(N-isopropylacrylamide)acrylamide copolymer, copolymer of poly(N-isopropylacrylamide) containing silane monomers selected from [3-(methacryloyloxy)propyl]trimethoxysilane, [2-(methacryloyloxy)ethoxy]-trimethylsilane and methacryloyloxy)trimethylsilane, copolymer of poly(hydroxypropyl methacrylamide), dicarboxymethylaminopropyl methacrylamide, xyloglucan, ethyl(hydroxyethyl)cellulose, poly(ethyleneoxide-b-propylene oxide-b-ethylene oxide) and its copolymers, poly(ethylene oxide)/(D,L-lactic acid-co-glycolic acid)copolymers, combinations of chitosan and polyol salts, poly(silamine), and poly(organophosphazene) or a combination thereof.
8 . An implantable drug depot according to claim 1 , wherein the reversible phase transition polymer is layered in the drug depot and the reversible phase transition polymer changes from solid to liquid to release the bolus dose of the analgesic, muscle relaxant and/or the anti-inflammatory agent when heat, cold or other energy form is applied to a site on the skin proximate to a site where the drug depot was implanted.
9 . An implantable drug depot according to claim 1 , wherein the reversible phase transition polymer comprises about 60% to 99% of the total weight % of the drug depot.
10 . An implantable drug depot according to claim 1 , wherein the heat applied to the skin is above about 40° C. to 45° C. to cause the reversible phase transition material in an implanted drug depot to change from solid to liquid or solid to semi-solid or semi-solid to liquid.
11 . An implantable drug depot according to claim 1 , wherein the cold applied to the skin is below 20° C. to 25° C. to cause the reversible phase transition material in an implanted drug depot to change from solid to liquid or solid to semi-solid or semi-solid to liquid.
12 . An implantable drug depot according to claim 1 , wherein the drug depot releases (i) a bolus dose of the analgesic and/or anti-inflammatory agent at a site beneath the skin over a period of up to 3 days and (ii) an effective amount of the analgesic and/or anti-inflammatory agent over a period of up to 6 months.
13 . A drug depot useful for reducing, preventing or treating pain and/or inflammation in a patient in need of such treatment, the drug depot being implantable at a site beneath the skin of the patient and comprising an effective amount of an analgesic, muscle relaxant, and/or an anti-inflammatory agent disposed within a reversible phase transition polymer and a biodegradable polymer of the drug depot, wherein the reversible phase transition material is capable of releasing a bolus dose of the analgesic, muscle relaxant and/or the anti-inflammatory agent when heat, cold or other energy form is applied at or near the drug depot and the biodegradable polymer is capable of releasing the analgesic, muscle relaxant and/or the anti-inflammatory agent over at least one day to reduce, prevent or treat pain and/or inflammation.
14 . A drug depot according to claim 13 , wherein the drug depot is implanted within 1 mm of an epidermis, dermis, or subcutaneous tissue and heat, cold or other energy form is applied to the skin to cause release of the bolus dose of the analgesic, muscle relaxant and/or the anti-inflammatory agent.
15 . A drug depot according to claim 13 , wherein the drug depot is in the form of a pellet.
16 . A drug depot according to claim 13 , wherein the heat is applied for about 5 minutes to about 60 minutes to the skin of the patient near the drug depot when it is implanted at the site beneath the skin.
17 . A drug depot according to claim 13 , wherein the cold is applied for about 5 minutes to about 60 minutes to the skin of the patient near the drug depot when it is implanted at the site beneath the skin.
18 . A method of treating or preventing pain and/or inflammation in a patient in need of such treatment, the method comprising implanting at a target tissue site beneath the skin of patient a biodegradable drug depot comprising an effective amount of an analgesic, muscle relaxant, and/or an anti-inflammatory agent disposed within a reversible phase transition material of the drug depot, wherein the reversible phase transition material is capable of releasing a bolus dose of the analgesic, muscle relaxant and/or the anti-inflammatory agent when heat, cold or other energy form is applied to or near the drug depot; and applying heat, cold or other energy form to or near the target tissue site where the drug depot is implanted to release the bolus dose of the analgesic, muscle relaxant and/or the anti-inflammatory agent to prevent or treat pain and/or inflammation.
19 . A method according to claim 18 , wherein the drug depot further comprises a biodegradable polymer that is capable of releasing the analgesic, muscle relaxant and/or the anti-inflammatory agent over at least one day to prevent or treat pain and/or inflammation.
20 . A method according to claim 18 , wherein (i) heat is applied to the skin of the patient and the heat is above about 40° C. to 45° C. to cause the reversible phase transition material to change from solid to liquid or solid to semi-solid or semi-solid to liquid to release the bolus dose or (ii) cold is applied to the skin of the patient and the cold is below about 20° C. to 25° C. to cause the reversible phase transition material to change from solid to liquid or solid to semi-solid or semi-solid to liquid to release the bolus dose.