Sustained-release injection formulation comprising conjugate of poly-l-lactic acid filler and hyaluronic acid filler and bioactive materials, and preparation method thereof

A method for producing a filler containing a PLLA-HA double microcapsule comprising:

• (a) mixing PLLA (poly-L-lactic acid) with CMC (carboxymethylcellulose) and mannitol, freeze-drying a resulting mixture, pulverizing the freeze-dried mixture to a certain size, and sterilizing a result thereof using gamma radiation to prepare a PLLA mixture;
• (b) mixing HA (hyaluronic acid) with a BDDE (butanediol diglycidyl ether) crosslinking agent, gelling a resulting mixture, washing a resulting gel with a phosphate buffer, collecting crosslinked HA with uniform particles and passing the HA through a screen to obtain crosslinked HA with uniform particles to thereby prepare a HA mixture;
• (c) homogenizing a primary core material (W1) containing a bioactive material, the PLLA mixture obtained in step (a), a biodegradable polymer, and an organic solvent to obtain a primary emulsion (W1/O);
• (d) adding distilled water to the crosslinked HA to obtain a secondary wall material (W2);
• (e) mixing the primary emulsion (W1/O) with the secondary wall material (W2) to obtain a PLLA-HA W/O/W emulsion;
• and
• (f) spray-drying the PLLA-HA W/O/W emulsion to prepare a double microcapsule.