Formulations and methods for providing prolonged local anesthesia

A formulation for inducing sustained regional local anesthesia in a patient comprising

• a plurality of substrates in a pharmaceutically acceptable medium for injection, said substrates comprising a local anesthetic and an effective amount of a biocompatible, biodegradable, controlled release material comprising a polymer selected from the group consisting of polyanhydrides, copolymers of lactic acid and glycolic acid, poly(lactic) acid, poly(glycolic) acid, polyesters, polyorthoesters, proteins, polysaccharides and combinations thereof, capable of degrading at least fifty percent in less than two years following implantation or injection into the patient, and prolonging the release of said local anesthetic from said substrates in-vitro, said substrates being included in said formulation in an amount sufficient to obtain reversible local numbness and/or analgesia when said formulation is implanted or injected in a patient, and
• a vasoconstricting agent selected from the group consisting of catecholamines, alpha-1 and alpha-2 adrenergic agonists, analogs thereof, active metabolites thereof, and mixtures thereof, said vasoconstricting agent being effective to prolong the duration of said local anesthesia for a time period longer than obtainable from said substrates without said vasoconstricting agent and included in a ratio from about 10:1 to about 20,000:1 relative to said local anesthetic said vasoconstricting agent being (i) incorporated into and/or onto said substrates;
• or (ii) incorporated into said pharmaceutically acceptable medium for injection, or (iii) incorporated into said substrates and also incorporated into said pharmaceutically acceptable medium for injection, said formulation providing an in vitro release of said local anesthetic using the USP/NF Paddle Method II of from about 10 to about 60 percent after 24 hours, from about 20 to about 80 percent release after 48 hours and from about 40 to about 100 percent release after 72 hours, said formulation providing a reversible local anesthesia at the site when administered in vivo of at least about 24 hours.

A formulation for inducing sustained regional local anesthesia in a patient comprising a plurality of substrates comprising a local anesthetic, a vasoconstricting agent, and an effective amount of a biocompatible, biodegradable controlled release material comprising a polymer selected from the group consisting of polyanhydrides, copolymers of lactic acid and glycolic acid, poly(lactic) acid, poly(glycolic) acid, polyesters, polyorthoesters, proteins, polysaccharides and combinations thereof, said biocompatible, biodegradable controlled release material being capable of degrading at least fifty percent in less than two years following implantation or injection into the patient and prolonging the release of said local anesthetic from said substrates, said substrates being included in said formulation in an amount sufficient to obtain reversible local numbness and/or analgesia when said formulation is implanted or injected in a patient, said vasoconstricting agent being selected from the group consisting of catecholamines, alpha-1 and alpha-2 adrenergic agonists, analogs thereof, active metabolites thereof, and mixtures thereof, said vasoconstricting agent being included in a ratio from about 10:1 to about 20,000:1 relative to said local anesthetic and prolonging the duration of said local anesthesia for a time period longer than that obtainable from said substrates without said vasoconstricting agent.