Prolonged anesthesia in joints and body spaces

Abstract

Sustained release local anesthetic formulations are administered intra articularly and/or into body spaces/cavities. The formulation is preferably a plurality of injectable microparticles including a local anesthetic and an effective amount of a biocompatible, biodegradable, sustained release material prolonging the release of the local anesthetic and optionally and a pharmaceutically acceptable, i.e., non-toxic, augmenting agent effective to prolong the duration of the local anesthesia for a time period longer than that obtainable without the augmenting agent.

What is claimed is:  
     
         1 . The use of a formulation comprising (a) controlled release microparticles comprising a local anesthetic and an effective amount of a biocompatible, biodegradable sustained release material prolonging the release of the local anesthetic from the formulation, and (b) a non-toxic augmenting agent in an amount effective to prolong the effect of the local anesthetic in-vivo, to treat localized joint pain or pain arising from a body space.  
     
     
         2 . The use of the formulation of  claim 1 , wherein at least a portion of said augmenting agent is incorporated into said microparticles.  
     
     
         3 . The use of the formulation of  claim 1 , wherein a plurality of microparticles are suspended in a pharmaceutically acceptable vehicle for injection.  
     
     
         4 . The use of the formulation of  claim 1 , wherein the formulation further comprises an active agent selected from the group consisting of an enzyme, an anti-infective agent, an antibody and combinations thereof.  
     
     
         5 . The use of the formulation of  claim 4 , wherein at least a portion of said further active agent is incorporated into said microparticles.  
     
     
         6 . The use of the formulation of  claim 1 , wherein said sustained release material is a polymer selected from the group consisting of polyanhydrides, copolymers of lactic acid and glycolic acid, poly(lactide) acid, poly(glycolic) acid, polyesters, polyorthoesters, proteins, polysaccharides and combinations thereof.  
     
     
         7 . The use of the formulation of  claim 1 , wherein the local anesthetic is incorporated into said microparticles at a percent loading of 0.1% to 90% by weight.  
     
     
         8 . The use of the formulation of  claim 1 , wherein the local anesthetic is selected from the group consisting of bupivacaine, ropivacaine, dibucaine, etidocaine, tetracaine, lidocaine, xylocaine, mixtures thereof, and salts thereof.  
     
     
         9 . The use of the formulation of  claim 1 , wherein the augmenting agent is a glucocorticosteriod.  
     
     
         10 . The use of the formulation of  claim 1 , wherein the local anesthetic is bupivacaine, the augmenting agent is dexamethasone, and the sustained release material is a poly(lactide co-glycolide).  
     
     
         11 . The use of the formulation of  claim 9 , wherein the glucocorticoid agent is selected from the group consisting of dexamethasone, cortisone, prednisone, hydrocortisone, beclomethasone dipropionate, betamethasone, flunisolide, methylprednisone, paramethasone, prednisolone, triamcinolone, alclometasone, amcinonide, clobetasol, fludrocortisone, diflorasone diacetate, fluocinolone acetonide, fluocinonide, fluorometholone, flurandrenolide, halcinonide, medrysone, and mixtures thereof.  
     
     
         12 . The use of the formulation of  claim 1 , wherein the microparticles comprise local anesthetic in a percent loading between 0.1% and 90%, preferably between 65 and 80%, and augmenting agent is a glucocorticosteroid agent present in a weight percent relative to the local anesthetic from 0.005% to 15%.  
     
     
         13 . The use of the formulation of  claim 1 , wherein the augmenting agent is an effective amount of a pharmaceutically acceptable vasoconstrictor agent.  
     
     
         14 . The use of the formulation of  claim 1 , for administration into a body space selected from pleura, peritoneium, cranium, mediastinum, pericardium, bursai, epidural, intrathecal, and intraocular, and which formulation provides pain relief for 3-5 days.  
     
     
         15 . The use of the formulation of  claim 1 , for administration into intra articular joints selected from knee, elbow, hip, sternoclavicular, temporomandibular, carpal, tarsal, wrist, ankle, and any other joint subject to arthritic conditions, and which formulation provides pain relief for 3-5 days.  
     
     
         16 . The use of the formulation of  claim 1 , for administration into a bursae selected from acromial, bicipitoradial, cubitoradial, deltoid, infrapetellar, ishchiadica, and other bursa known to those skilled in the art to be subject to pain, and which formulation provides pain relief for 3-5 days.  
     
     
         17 . The use of a formulation comprising (a) controlled release microparticles comprising a local anesthetic and an effective amount of a biocompatible, biodegradable sustained release polymer selected from polyanhydrides, copolymers of lactic acid and glycolic acid, poly(lactic) acid, poly(glycolic) acid, polyesters, polyorthoesters, proteins, polysaccharides and combinations thereof, providing an in-vitro release of said local anesthetic of from 10 to 60 percent after 24 hours, from 20 to 80 percent release after 48 hours, and from 40 to 100 percent release after 72 hours; and (b) a non-toxic augmenting agent in an amount effective to prolong the effect of the local anesthetic in-vivo, for providing pain relief a body space selected from pleura, peritoneium, cranium, mediastinum, pericardium, bursai, epidural, intrathecal, and intraocular, or from intra articular joints selected from knee, elbow, hip, sternoclavicular, temporomandibular, carpal, tarsal, wrist, ankle, and any other joint subject to arthritic conditions, or from bursae selected from acromial, bicipitoradial, cubitoradial, deltoid, infrapetellar, ishchiadica, and other bursa known to those skilled in the art to be subject to pain, and which formulation when administered in-vivo for at least about 24 hours, and preferably for 3-5 days.  
     
     
         18 . The use of the formulation of  claim 17 , which further comprises a second active agent selected from an enzyme, an anti-infective agent, an antibody, a diagnostic aid, a radio-opaque dye, a magnetic resonance imaging dye, a radiolabeled agent, and combinations thereof.