Hyaluronic acid based formulations

Abstract

Disclosed herein are soft tissue fillers, for example, dermal and subdermal fillers, based on low molecular weight hyaluronic acids and pharmaceutically acceptable salts thereof, and methods of manufacturing same.

What is claimed is: 
     
         1 . A method of adding volume to the lip of a patient, the method comprising injecting a sterile composition into the lip of the patient in need thereof, the sterile composition comprising:
 a soft tissue filler comprising a crosslinked hyaluronic acid (HA) 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;   wherein the HA concentration of the filler is about 17 mg/g;   wherein the method adds volume to the lip of the patient for a period of time in the range of about 9 months to about 12 months after injection of the filler into the lip of the patient.   
     
     
         2 . The method of  claim 1  wherein the HA concentration is about 17.5 mg/g. 
     
     
         3 . The method of  claim 1  wherein the method is effective to add volume to the lip of the patient for about 12 months after injection of the filler into the lip of the patient. 
     
     
         4 . The method of  claim 1  wherein the filler is a filler made with a mixture of low molecular weight hyaluronic acid and high molecular weight hyaluronic acid. 
     
     
         5 . The method of  claim 1  wherein the filler further comprises at least one anesthetic agent. 
     
     
         6 . The method of  claim 1  wherein the composition has a degree of crosslinking of between about 4% and about 12%. 
     
     
         7 . The method of  claim 1  wherein the composition has a degree of crosslinking of about 6%. 
     
     
         8 . The method of  claim 1  wherein the composition has a degree of crosslinking of about 5%. 
     
     
         9 . A method of reducing the appearance of nasolabial folds of a patient, the method comprising injecting a sterile composition into the nasolabial folds of a patient in need thereof, the sterile composition comprising:
 a soft tissue filler comprising a crosslinked hyaluronic acid (HA) 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;   wherein the HA concentration of the filler is about 17 mg/g;   wherein the method reduces the appearance of nasolabial folds of the patient for a period of time in the range of about 9 months to about 12 months after injection of the filler into the nasolabial folds of the patient.   
     
     
         10 . The method of  claim 9  wherein the HA concentration is about 17.5 mg/g. 
     
     
         11 . The method of  claim 10  wherein the method is effective to reduce the appearance of nasolabial folds of the patient for about 12 months after injection of the filler into the nasolabial folds of the patient. 
     
     
         12 . The method of  claim 9  wherein the method is effective to reduce the appearance of nasolabial folds of the patient for about 12 months after injection of the filler into the nasolabial folds of the patient. 
     
     
         13 . The method of  claim 9  wherein the filler is a filler made with a mixture of low molecular weight hyaluronic acid and high molecular weight hyaluronic acid. 
     
     
         14 . The method of  claim 9  wherein the filler further comprises at least one anesthetic agent. 
     
     
         15 . The method of  claim 9  wherein the composition has a degree of crosslinking of between about 4% and about 12%. 
     
     
         16 . The method of  claim 9  wherein the composition has a degree of crosslinking of about 6%. 
     
     
         17 . The method of  claim 9  wherein the composition has a degree of crosslinking of about 5%. 
     
     
         18 . A method of treating an age-related condition of the midface of a patient in need thereof, the method comprising injecting a sterile composition into the midface of the patient, the sterile composition comprising:
 a soft tissue filler comprising a crosslinked hyaluronic acid (HA) 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 at least one anesthetic agent;   wherein the HA concentration of the filler is about 17.5 mg/g;   wherein the composition is effective in treating the age-related condition of the midface for a period of time in the range of about 9 months to about 12 months after injection of the filler into the midface of the patient.   
     
     
         19 . The method of  claim 18  wherein the age-related condition is volume loss. 
     
     
         20 . The method of  claim 18  wherein the composition has a degree of crosslinking of about 6%. 
     
     
         21 . The method of  claim 18  wherein the filler is a filler made with a mixture of low molecular weight hyaluronic acid and high molecular weight hyaluronic acid.