Method to prepare a filler with hyaluronic acid base comprising a neutralization step

A method to prepare a filler with a hyaluronic acid base comprising the following steps:

• A) crosslinking hyaluronic acid by mixing the following components in a reaction chamber to form a reaction mixture:
• water, hyaluronic acid (HA), a crosslinking agent chosen from the class of polyethylene glycols (PEGs), and a solution of alkali metal hydroxide, a mixing time of between 10 minutes and 40 minutes to obtain a gel of crosslinked HA;
• B) a chemical neutralization step of the gel of crosslinked HA obtained in step A), comprising:
• B1) preparing a single neutralization solution by mixing the following components:
• water, hydrochloric acid (HCl), a buffering agent, and lidocaine or derivatives of lidocaine;
• B2) dividing the single neutralizing solution thus obtained into a number n of partial portions and thereafter transferring one of each said n partial portions inside each of the n containers containing a portion of the gel of crosslinked HA obtained from step A) to form a mixture, where n is a number between 4 and 32;
• B3) subjecting to mixing the mixture in each of the n containers by a rotary device, making the containers rotate around the axis of the rotary device to promote a penetration of the neutralizing solution inside the gel of hyaluronic acid, and obtain a hydrogel filler of crosslinked HA, wherein in said step B1) a percentage in weight (w/w) of individual components with respect to a total weight of the neutralization solution is as follows:
• from 78% to 98% water;
• from 4% to 25% hydrochloric acid;
• from 0.1% to 1.5% buffering agent;
• and,
• up to 1.5% in weight of lidocaine or derivatives of lidocaine.