Dexamethasone formulations in a biodegradable material

• US 8,524,267 B2
• Filed: 04/18/2008
• Issued: 09/03/2013
• Est. Priority Date: 04/18/2008
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc), Warsaw Orthopedic Incorporated (Medtronic Plc)
• Original Assignee: Warsaw Orthopedic Incorporated (Medtronic Plc)
• Inventors: Zanella, John, King, Vanja, Hobot, Christopher M., Cox, Stephen M., McKay, William, Remsen, Kathy
• Primary Examiner(s): BARHAM, BETHANY P
• Application Number:
  US12/105,864
• Publication Number:
  US 20090263455A1
• Time in Patent Office: 1,964 Days
• Field of Search: None
• US Class Current: 424/426
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• 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: 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

Abstract

Effective treatments of acute pain for extended periods of time are provided. Through the administration of an effective amount of dexamethasone at or near a target site, one can relieve pain cause by diverse sources, including but not limited to spinal disc herniation (i.e. sciatica), spondilothesis, stenosis, discongenic 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 twenty-five days. In some embodiments, the relief can be for 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 for reducing, preventing or treating pain and/or inflammation in a patient in need of such treatment, the implantable drug depot comprising dexamethasone in an amount from about 2 wt. % to about 20 wt. % of the drug depot, and at least one biodegradable polymer comprising at least 80 wt. % of the drug depot, wherein the drug depot releases a bolus dose of the dexamethasone at a site beneath the skin and releases an effective amount of the dexamethasone over a period of at least fifty days and the polymer comprises poly(lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide (PGA), or poly(orthoester), D-lactide, D,L-lactide, L-lactide, D,L-lactide-caprolactone, D,L-lactideglycolide-caprolactone or a combination thereof and the drug depot comprises an adherent gel that stiffens after delivery to a target site having a pre-dosed modulus of elasticity in the range of about 5×

10⁴ to about 1×

10⁵ dynes/cm² and a post-dose modulus of elasticity in the range of about 2×

10⁵ to about 5×

10⁵ dynes/cm².

2. An implantable drug depot according to claim 1, wherein said dexamethasone comprises from about 5 wt. % to about 10 wt. % of the drug depot.

3. An implantable drug depot according to claim 1, wherein said at least one biodegradable material comprises at least 90 wt. % of the drug depot.

4. An implantable drug depot according to claim 1, wherein the polymer comprises poly(lactic-co-glycolic acid) or poly(orthoester) or both.

5. An implantable drug depot according to claim 4, wherein the polymer comprises poly(lactic-co-glycolic acid) and said poly(lactic-co-glycolic acid) comprises a mixture of polyglycolide and polylactide.

6. An implantable drug depot according to claim 5, wherein said mixture comprises more polylactide than polyglycolide.

9. A method for treating pain and/or inflammation, wherein said method comprises implanting an implantable drug depot of claim 1 in an organism to reduce, prevent or treat pain.

10. A method according to claim 9, wherein said dexamethasone comprises from about 5 wt. % to about 10 wt. % of the drug depot.

11. A method according to claim 9, wherein said biodegradable polymer comprises at least 85 wt. % of the drug depot.

12. A method according to claim 9, wherein said biodegradable polymer comprises at least 95 wt. % of the drug depot.

13. A method according to claim 9, wherein the at least one biodegradable polymer comprises poly(lactic-co-glycolic acid) or poly(orthoester) or both.

14. A method according to claim 13, wherein the at least one biodegradable polymer comprises poly(lactic-co-glycolic acid) and said poly(lactic-co-glycolic acid) comprises a mixture of polyglycolide and polylactide.

15. A method according to claim 14, wherein said mixture comprises more polylactide than polyglycolide.

16. A method according to claim 9, wherein said implanting comprises applying said drug depot at a plurality of sites that triangulate a pain generator.

17. A method of making an implantable drug depot of claim 1, the method comprising combining a biocompatible polymer and a therapeutically effective amount of dexamethasone or a pharmaceutically acceptable salt thereof and forming the implantable drug depot from the combination.

18. An implantable drug depot according to claim 1, wherein the dexamethasone is evenly distributed throughout the gel.

20. An implantable drug depot according to claim 1, wherein the gel includes a viscosity enhancing agent comprising hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl methylcellulose, carboxymethylcellulose and salts thereof, Carbopol, poly-(hydroxyethylmethacrylate), poly-(methoxyethylmethacrylate), poly(methoxyethoxyethyl methacrylate), polymethylmethacrylate (PMMA), methylmethacrylate (MMA), gelatin, polyvinyl alcohols, propylene glycol, mPEG, 800, PEG 900, PEG 1000, PEG 1450, PEG 3350, PEG 4500, PEG 8000, or a combination thereof.

7. An implantable drug depot for reducing, preventing or treating pain and/or inflammation in a patient in need of such treatment, the implantable drug depot comprising dexamethasone in an amount of from about 2 wt. % to about 15 wt. % of the drug depot, nonpolymeric SAIB (sucrose acetate isobutyrate) and at least one biodegradable polymer, wherein the at least one biodegradable polymer comprises polylactide (PLA) or a combination thereof, and said at least one biodegradable polymer comprises at least 80 wt. % of said drug depot, wherein the drug depot releases a bolus dose of the dexamethasone at a site beneath the skin and releases an effective amount of the dexamethasone over a period of at least fifty days and the drug depot comprises an adherent gel that stiffens after deliver to a target site having a pre-dosed modulus of elasticity in the range of about 5×

10⁴ to about ×

10⁵ dynes/cm² and a post-dosed modulus of elasticity in the range about 2×

10⁵ to about 5×

10⁵ dynes/cm².

8. An implantable drug depot according to claim 7, wherein the at least one polymer comprises one or more of poly(lactide-co-glycolide), D-lactide, D,L-lactide, L-lactide, D,L-lactide-caprolactone, and D,L-lactide-glycolide-caprolactone.

19. An implantable drug depot according to claim 7, wherein dexamethasone is evenly distributed throughout the gel.