Biodegradable polymer matrices for sustained delivery of local anesthetic agents

• US 5,618,563 A
• Filed: 09/10/1993
• Issued: 04/08/1997
• Est. Priority Date: 09/10/1992
• Status: Expired due to Term

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Langer, Robert S., Berde, Charles B.
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US08/119,958
• Time in Patent Office: 1,306 Days
• Field of Search: 424/484, 424/486, 424/488, 424/499, 424/501, 424/465, 424/468, 424/456, 424/422-423, 424/490, 514/772.7, 264/DIG. 65, 264/12, 264/13, 264/301, 264/309, 264/322, 425/DIG. 245
• US Class Current: 424/501
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• 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 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61P 25/02 for peripheral neuropathies

Abstract

An improved biodegradable controlled release system consisting of a polymeric matrix incorporating a local anesthetic for the prolonged administration of the local anesthetic agent, and a method for the manufacture thereof, are disclosed. The polymers and method of manufacture used to form the PLAMs are selected on the basis of their degradation profiles: release of the topical anesthetic in a linear, controlled manner over a period of preferably two weeks and degradation in vivo with a half-life of less than six months, more preferably two weeks, to avoid localized inflammation. Alternatively, a non-inflammatory can be incorporated into the polymer with the local anesthetic to prevent inflammation.

Claims

1. A method for sustained local anesthesia or regional nerve blockade at a site in a patient, the improvement comprising

administering by injection into tissue a local anesthetic incorporated into microparticles formed of a biocompatible polymer degrading at least fifty percent in less than six months following injection into the patient which is selected from the group consisting of polyanhydrides, copolymers of lactic acid and glycolic acid, poly(glycolic acid), polyorthoesters, proteins, and polysaccharides,

wherein the local anesthetic is uniformly incorporated into the microparticles in a concentration effective to achieve sustained release of anesthetic at the site for at least three days following injection of the microparticles.

2. The method of claim 1 wherein the microparticles are selected from the group consisting of microspheres and microcapsules.

3. The method of claim 1 wherein the local anesthetic is selected from the group consisting of bupivacaine, dibucaine, etidocaine, tetracaine, lidocaine, xylocaine and salts thereof.

4. The method of claim 1 wherein the local anesthetic is incorporated into the microparticles at a percent loading of between 0.1% and 70% by weight.

5. The method of claim 1 wherein the microparticles are made using a hot melt process.

6. The method of claim 1 wherein the polymer does not elicit inflammation following injection of the microparticles into a patient.

7. The method of claim 2 further comprising administering the microparticles in combination with a pharmaceutically acceptable carrier by injection.