Sensory-Specific Local Anesthesia and Prolonged Duration Local Anesthesia

Abstract

Combinations of charged local anesthetics with chemical permeation enhancers have been developed to give long duration block which is selective for sensory block is greatly prolonged by combining the local anesthetic with a permeation enhancer. The selectivity of sensory over motor block is provided by selecting the concentration of the local anesthetic and the permeation enhancer to provide selective permeability of the sensory and motor neurons to the enhancer.

We claim: 
     
         1 . A method for selective sensory nerve blockade comprising administering a combination of a charged local anesthetic selected from the group consisting of amino-amide or amino-ester local anesthetics or derivatives thereof at least partly amphiphilic local anesthetics, local anesthetics that act not on the outer surface of the cell, and at least partly charged local anesthetics, and
 a chemical permeation enhancer selected from the group consisting of surfactants, terpenes, amino amides, amino esters, azide-like compounds and alcohols, in a suitable pharmaceutically acceptable carrier.   
     
     
         2 . The method of  claim 1  wherein the local anesthetic comprises an excipient having a pH rendering the local anesthetic charged. 
     
     
         3 . The method of  claim 1  further comprising administering the local anesthetic and chemical permeation enhancer with a vasoconstrictor. 
     
     
         4 . The method of  claim 1  wherein the duration of block is prolonged by combining the local anesthetic with a permeation enhancer, as compared to duration of block in the absence of permeation enhancer. 
     
     
         5 . The method of  claim 1  wherein the local anesthetic is a charged lidocaine derivative. 
     
     
         6 . The method of  claim 5  wherein the local anesthetic is QX-314. 
     
     
         7 . The method of  claim 1  wherein the chemical penetration enhancer is an anionic, nonionic or cationic surfactant. 
     
     
         8 . The method of  claim 7  wherein the chemical permeation enhancer is selected from the group consisting of octyltriethylammonium bromide (OTAB) and TWEEN 20 (polysorbate 20). 
     
     
         9 . The method of  claim 1  wherein the local anesthetic and chemical permeation enhancer is administered as a bolus dosage unit. 
     
     
         10 . The method of  claim 1  wherein the local anesthetic and chemical permeation enhancer is administered in a continuous or sustained release formulation. 
     
     
         11 . The method of  claim 1  wherein the local anesthetic and chemical permeation enhancer is administered in a topical or aerosol formulation. 
     
     
         12 . The method of  claim 1  further comprising a site I sodium channel blocker. 
     
     
         13 . The method of  claim 1  wherein the local anesthetic and chemical permeation enhancer is administered by injection. 
     
     
         14 . The method of  claim 1  wherein the local anesthetic and chemical permeation enhancer cause greater sensory block than motor block. 
     
     
         15 . A composition for selective sensory nerve blockade comprising a combination of
 a charged local anesthetic selected from the group consisting of amino-amide or amino-ester local anesthetics or derivatives thereof, at least partly amphiphilic local anesthetics, local anesthetics that act not on the outer surface of the cell, and at least partly charged local anesthetics, and
 a chemical permeation enhancer selected from the group consisting of surfactants, terpenes, amino amides, amino esters, azide-like compounds and alcohols, in a suitable pharmaceutically acceptable carrier. 
   
     
     
         16 . The composition of  claim 15  wherein the local anesthetic comprises an excipient having a pH rendering the local anesthetic charged. 
     
     
         17 . The composition of  claim 15  further comprising administering the local anesthetic and chemical permeation enhancer with a vasoconstrictor. 
     
     
         18 . The composition of  claim 15  wherein the duration of block is prolonged by combining the local anesthetic with a permeation enhancer, as compared to duration of block in the absence of permeation enhancer. 
     
     
         19 . The composition of  claim 15  wherein the local anesthetic is a charged lidocaine derivative. 
     
     
         20 . The composition of  claim 19  wherein the local anesthetic is QX-314. 
     
     
         21 . The composition of  claim 15  wherein the chemical penetration enhancer is an anionic, nonionic or cationic surfactant. 
     
     
         22 . The composition of  claim 19  wherein the chemical permeation enhancer is OTAB or polysorbate 20. 
     
     
         23 . The composition of  claim 15  in a bolus dosage unit. 
     
     
         24 . The composition of  claim 15  in a continuous or sustained release formulation. 
     
     
         25 . The composition of  claim 15  in a topical or aerosol formulation. 
     
     
         26 . The composition of  claim 15  further comprising a site I sodium channel blocker. 
     
     
         27 . The composition of  claim 15  wherein the local anesthetic and chemical permeation enhancer cause greater sensory block than motor block.