FIELD: pharmaceuticals.
SUBSTANCE: invention relates to the field of medicine, namely, to a method for producing a filler containing dual PLLA-HA microcapsules, wherein: (a) PLLA (poly-L-lactic acid) is mixed with CMC (carboxymethyl cellulose) and mannitol, the resulting mixture is freeze-dried, the dried mixture is crushed to a certain size, and the mixture is sterilised using gamma radiation, producing a PLLA mixture; (b) HA (hyaluronic acid) is mixed with a crosslinking agent BDDE (butanediol diglycidyl ether), the resulting mixture is gelatinised, the resulting gel is washed with a phosphate buffer, the crosslinked HA with identical particles is collected, and the HA is passed through a sieve, resulting in crosslinked HA with identical particles, producing an HA mixture; (c) the primary core material (W1) containing a medicinal product containing an analgesic and/or an antibiotic, the PLLA mixture produced at stage a), a biodegradable polymer, and an organic solvent are homogenised, producing a primary emulsion (W1/O); (d) distilled water is added to the crosslinked HA, producing an auxiliary wall material (W2); (e) the primary emulsion (W1/O) is mixed with the auxiliary wall material (W2), producing a PLLA-HA W/O/W emulsion; and (f) the PLLA-HA W/O/W emulsion is spray-dried, producing dual microcapsules, wherein the freeze drying at stage (a) includes: primary freeze drying from -60 to -100°C for 12 to 24 hours; and additional drying from 15 to 25°C for 5 to 10 days, and the size of the crushed particles is in the range from 30 to 100 mcm; and wherein the spray drying is performed at a temperature of the supplied air from 125 to 135°C, a temperature of the released air from 75 to 85°C, rotation of the sprayer of 10×10 kPa, blowing speed of 0.80 m3/min, and pump speed of 1.0 ml/min.
EFFECT: invention provides a conjugate of a filler with poly-L-lactic acid (PLLA) and a filler with hyaluronic acid (HA); and a dual microcapsule with delayed release of a PLLA-HA conjugate, containing a high amount of the conjugate, capable of stable release of the medicinal product for a long period of time, and containing easily applicable identical particles; and also consists in the method for production thereof.
5 cl, 3 ex
