Hyaluronic acid-based gels including lidocaine

Abstract

Disclosed herein are cohesive soft tissue fillers, for example, dermal and subdermal fillers, based on hyaluronic acids and pharmaceutically acceptable salts thereof. In one aspect, hyaluronic acid-based compositions described herein include a therapeutically effective amount of at least one anesthetic agent, for example, lidocaine. The present hyaluronic acid-based compositions including lidocaine have an enhanced stability and cohesivity, relative to conventional compositions including lidocaine, for example when subjected to sterilization techniques or when stored for long periods of time. Methods and processes of preparing such hyaluronic acid-based compositions are also provided.

What is claimed is: 
     
         1 . A soft tissue filler composition comprising:
 a fluid, soluble hyaluronic acid (HA) medium;   crosslinked HA particles dispersed in the fluid, soluble HA medium; and   lidocaine.   
     
     
         2 . The soft tissue filler composition of  claim 1 , wherein the crosslinked HA particles are crosslinked with a crosslinking agent selected from the group consisting of 1,4-butanediol diglycidyl ether (BDDE), 1,4-bis(2,3-epoxypropoxy)butane, 1,4-bisglycidyloxybutane, 1,2-bis(2,3-epoxypropoxy)ethylene and 1-(2,3-epoxypropyl)-2,3-epoxycyclohexane, and combinations thereof. 
     
     
         3 . The soft tissue filler composition of  claim 2 , wherein the crosslinked HA particles are crosslinked with BDDE. 
     
     
         4 . The soft tissue filler composition of  claim 1 , wherein the crosslinked HA particles have a degree of crosslinking between about 2% and up to about 20%. 
     
     
         5 . The soft tissue filler composition of  claim 1 , wherein the fluid, soluble HA medium includes free HA. 
     
     
         6 . The soft tissue filler composition of  claim 1 , comprising about 80 wt % crosslinked HA particles. 
     
     
         7 . The soft tissue filler composition of  claim 1 , wherein the lidocaine is present in a concentration between about 0.1% to about 5.0% by weight. 
     
     
         8 . The soft tissue filler composition of  claim 1 , wherein the lidocaine is freely released in vivo. 
     
     
         9 . The soft tissue filler composition of  claim 1 , wherein the pH of the soft tissue filler composition is between about 7.2 and 8.0. 
     
     
         10 . The soft tissue filler composition of  claim 1 , wherein the soft tissue filler composition is sterile and stable.