US 11,865,225 B2
Sustained release injectable formulation containing a poly L lactic acid filler and a hyaluronic acid filler conjugate and a method for preparing the same
Chang Sik Kim, Suwon-si (KR)
Assigned to GCS Co., Ltd., Seongnam-si (KR)
Appl. No. 17/057,924
Filed by GCS Co., Ltd., Seongnam-si (KR)
PCT Filed Nov. 6, 2020, PCT No. PCT/KR2020/015514
§ 371(c)(1), (2) Date Nov. 23, 2020,
PCT Pub. No. WO2021/101140, PCT Pub. Date May 27, 2021.
Claims priority of application No. 10-2019-0151407 (KR), filed on Nov. 22, 2019.
Prior Publication US 2021/0369913 A1, Dec. 2, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61L 27/26 (2006.01); A61K 9/50 (2006.01); A61L 27/54 (2006.01); A61K 9/00 (2006.01); A61K 9/16 (2006.01); A61K 31/167 (2006.01); A61K 31/4178 (2006.01); A61K 31/431 (2006.01); A61K 31/445 (2006.01); A61K 31/496 (2006.01); A61K 31/5383 (2006.01); A61K 31/665 (2006.01); A61K 31/7036 (2006.01); A61K 31/7056 (2006.01); A61L 27/58 (2006.01)
CPC A61L 27/26 (2013.01) [A61K 9/5031 (2013.01); A61K 9/5036 (2013.01); A61K 9/5073 (2013.01); A61K 9/5089 (2013.01); A61K 31/167 (2013.01); A61K 31/4178 (2013.01); A61K 31/431 (2013.01); A61K 31/445 (2013.01); A61K 31/496 (2013.01); A61K 31/5383 (2013.01); A61K 31/665 (2013.01); A61K 31/7036 (2013.01); A61K 31/7056 (2013.01); A61L 27/54 (2013.01); A61L 27/58 (2013.01); A61L 2300/406 (2013.01); A61L 2300/622 (2013.01)] 5 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 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 phosphate buffer solution in which a drug containing a pain reliever and/or antibiotic is dissolved, the PLLA mixture obtained in step (a), a biodegradable polymer, MCT (medium-chain triglyceride) oil and PGPR (polyglycerol polyricinoleate) to obtain a primary emulsion (W1/O),
wherein the biodegradable polymer comprises at least one selected from the group consisting of polydioxanone, poly-(ε-caprolactone), poly(lactic-co-glycolic acid), polylactide-co-ε-caprolactone, poly-L-lactide, polylactic acid, polyglycolic acid, polyhydroxy-valeric acid, polyphosphoester, polyethylene oxide-polylactic acid, polyethylene oxide-polylactic-co-glycolic acid, polyethylene oxide-poly-ε-caprolactone, poly-4-hydroxybutyrate, and chitosan;
(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 double microcapsules,
wherein the spray-drying is performed under the condition that a fed air temperature is between 125° C. to 135° C., a discharge air temperature is between 75° C. to 85° C., a rotary sprayer is 10×10 kPa, a blower speed is 0.80 m3/min, and a pump speed is 1.0 mL/min.