Treatment Methods with Low-Dose, Longer-Acting Formulations of Local Anesthetics and Other Agents

• US 20140105989A1
• Filed: 12/23/2013
• Published: 04/17/2014
• Est. Priority Date: 06/13/2003
• Status: Abandoned Application

• Current Assignee: Lyotropic Therapeutics, LLC
• Original Assignee: Lyotropic Therapeutics Inc.
• Inventors: Anderson, David, Cameransi, Benjamin G. Jr.
• Application Number:
  US14/138,279
• Publication Number:
  US 20140105989A1
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/24 having an amino or nitro group
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• 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 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 9/1274 Non-vesicle bilayer structures, e.g. liquid crystals, tubules, cubic phases, cochleates; Sponge phases
• CPC Class Codes: A61K 9/141 Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers (co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50

Abstract

Drug formulations that provide sustained action and/or reduced dosage requirements are provided. In the formulations the drugs (particularly local anesthetics) are associated with reversed cubic phase and reversed hexagonal phase lyotropic liquid crystalline material.

Claims

1-145. -145. (canceled)

146. A local anesthetic formulation having prolonged duration of action for a given dose, comprising:

a local anesthetic selected from the group consisting of bupivacaine and ropivacaine at a given dose;

microparticles of reversed cubic or reversed hexagonal lyotropic liquid crystalline phase material or combinations thereof ; and

a polar solvent,

wherein said microparticles are dispersed in said polar solvent,

wherein said local anesthetic is solubilized in said microparticles,

wherein said given dose of said local anesthetic has a first duration of action in the absence of said microparticles and said polar solvent, and has a second duration of action which is greater than said first duration of action when said local anesthetic is solubilized in said microparticles and said microparticles are dispersed in said polar solvent.

147. The local anesthetic formulation of claim 146 wherein said local anesthetic formulation produces a duration of nerve block of at least eight hours in a rat paw withdrawal nerve block model when said given dose is an amount equal to a standard therapeutic dose.

148. The local anesthetic formulation of claim 146 wherein said local anesthetic formulation does not include a vasoconstrictive agent.

149. The local anesthetic formulation of claim 146 wherein said microparticles are uncoated and a zeta potential of said microparticles in said formulation equals or exceeds 25 millivolts in magnitude.

150. The local anesthetic formulation of claim 146 wherein said microparticles are coated.

151. The local anesthetic formulation of claim 146 wherein said microparticles have an average size of less than 1.0 micron.

152. The local anesthetic formulation of claim 146 wherein said microparticles have an average size of less than 0.5 micron.

153. The local anesthetic of claim 146 wherein said second duration of action is at least 50% greater than said first duration of action.

155. The method of claim 153 wherein said step of administering is performed by injection.

156. The method of claim 153 wherein said step of administering is performed by spraying or nebulization.

154. A method of providing prolonged anesthesia to a subject, comprising administering to said subject a local anesthetic formulation having

a local anesthetic selected from the group consisting of bupivacaine and ropivacaine at a given dose;

microparticles of reversed cubic or reversed hexagonal lyotropic liquid crystalline phase material or combinations thereof ; and

a polar solvent,

wherein said microparticles are dispersed in said polar solvent,

wherein said local anesthetic is solubilized in said microparticles,

wherein said given dose of said local anesthetic has a first duration of action in the absence of said microparticles and said polar solvent, and has a second duration of action which is greater than said first duration of action when said local anesthetic is solubilized in said microparticles and said microparticles are dispersed in said polar solvent.