Baclofen formulation in a polyorthoester carrier

• US 8,475,823 B2
• Filed: 04/17/2009
• Issued: 07/02/2013
• Est. Priority Date: 04/18/2008
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Hobot, Christopher M., Benz, Michael E., Hildebrand, Keith R., Pudil, Bryant J.
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Park, H. Sarah
• Application Number:
  US12/426,021
• Publication Number:
  US 20090208554A1
• Time in Patent Office: 1,537 Days
• Field of Search: None
• US Class Current: 424/423
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• 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 9/0024 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

Abstract

Effective treatments of 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 baclofen 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 in an amount of about 95 to 99 wt. % based on the total weight of the drug depot, the polyorthoester having a viscosity of about 500 to 10,000 centipoises and prepared from trans-cylcohexanedimethanol, 1,6-hexanediol, and diethyltartrate;

baclofen in an amount of about 1 to 5 wt. % based on the total weight of the drug depot and having a particle size of between about 5 μ

m to 50 μ

m;

magnesium oxide; and

at least one of sorbitane tristearate, sorbitane trioleate, poloxamer 407, sorbital, cyclodextrin, maltodextrin, or poloxamer 188,

wherein the drug depot is adapted to be administered intraspinally in the patient to reduce or treat pain, has a modulus of elasticity in the range of about 2×

10⁴ to about 5×

10⁵ dynes/cm² after the drug depot is administered at the site, and capable of releasing baclofen for a period of 30 to 180 days after administration; and

the polyorthoester is capable of degrading in 200 days or less after the drug depot is administered at the site.

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

3. 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-c-caprolactone, dextran, polyvinylpyrrolidone, polyvinyl alcohol, PEGT-PBT (polyethylene terephthalate glycol-polybutylene terephthalate) copolymer, PEO-PPO-PEO (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) tri-block copolymers, sucrose acetate isobutyrate, a different polyorthoester or a combination thereof.

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

5. An implantable drug depot according to claim 1, wherein the drug depot is in the form of a ribbon, rod or pellet.

6. An implantable drug depot according to claim 1, wherein the drug depot releases about 0.5 mg to about 20 mg of the baclofen over a period of 30 days.