US 12,115,283 B2
Sustained-release injection formulation comprising conjugate of poly-L-lactic acid filler and hyaluronic acid filler and bioactive materials, and preparation method thereof
Chang Sik Kim, Suwon-si (KR)
Assigned to GCS CO., LTD., Seongnam-si (KR)
Appl. No. 17/420,182
Filed by GCS CO., LTD., Seongnam-si (KR)
PCT Filed Nov. 6, 2020, PCT No. PCT/KR2020/015520
§ 371(c)(1), (2) Date Jul. 1, 2021,
PCT Pub. No. WO2021/101141, PCT Pub. Date May 27, 2021.
Claims priority of application No. 10-2019-0151423 (KR), filed on Nov. 22, 2019.
Prior Publication US 2022/0088276 A1, Mar. 24, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61L 27/54 (2006.01); A61L 27/48 (2006.01)
CPC A61L 27/54 (2013.01) [A61L 27/48 (2013.01); A61L 2300/604 (2013.01); A61L 2300/622 (2013.01); A61L 2400/06 (2013.01)] 6 Claims
 
1. 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 the resulting mixture, pulverizing the freeze-dried mixture to a size of 30 to 100 μm, and sterilizing the result thereof using gamma radiation to prepare a PLLA mixture;
(b) mixing HA (hyaluronic acid) with a BDDE (butanediol diglycidyl ether) crosslinking agent, gelling the resulting mixture, washing the resulting gel with a phosphate buffer, collecting the crosslinked HA and passing the crosslinked 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 HA mixture obtained in step (b) 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.