Development of Dispersion Process to Improve Quality of Hyaluronic Acid Filler Crosslinked with 1,4-Butanediol Diglycidyl Ether

This study proposes a new and simple process that improves the quality of a hyaluronic acid (HA) filler crosslinked with 1,4-butanediol diglycidyl ether (BDDE) using solution dispersion at a low temperature. This process involves the solvent being dispersed among the solute naturally after the mixing process. The process used in this study involved two reactions. First, the solution was dispersed among HA molecules (Mw = ~0.7 MDa) creating a well-homogenized mixture. Second, the decomposition and synthesis of HA occurred naturally in an aqueous alkaline solution (>pH 11), the weight average molar mass (Mw) was adjusted (Mw = ~143,000), and the crosslinking surface area was expanded, allowing for a high degree of crosslinking. Therefore, the viscoelasticity and cohesion of the filler increased with the new method compared to the previous process both at the lab scale (previous process:new process, viscosity (cP) = 24M:43M, storage modulus (Pa) = 306:538, loss modulus (Pa) = 33:61, and tack (N) = 0.24:0.43) and at the factory scale (previous process:new process, complex viscosity (cP) = 19M:26M, storage modulus (Pa) = 229:314, loss modulus (Pa) = 71:107, and tack (N) = 0.35:0.43).