FIELD: medicine; pharmaceutics.
SUBSTANCE: group of inventions relates to a method of producing a prolonged release pharmaceutical composition, comprising: (a) spray drying of an aqueous solution, containing from 25 mg/ml to 50 mg/ml of protein trap of vascular endothelial growth factor (trap-VEGF), to form a set of protein trap particles-VEGF by dispersing the protein trap-VEGF solution and drying it by spray drying to form micro-milled protein particles, where the spray dryer inlet temperature is set at a level higher than the water boiling point, and the outlet temperature is set at the temperature below the water boiling point and above the ambient temperature, and wherein the therapeutic protein solution is pumped into the spray drier at rate of 2 ml/min to 15 ml/min; and (b) suspension of micro-milled particles of trap protein-VEGF in organic solution, containing a biodegradable polymer selected from polyorthoester or ethylcellulose and an organic solvent; and (c) spray drying of suspension (b) to form a set of polymeric protein microparticles of trap-VEGF, wherein said prolonged release pharmaceutical composition comprises (i) trap-VEGF protein particles coated with a biodegradable polymer, or (ii) collection of polymeric protein particles of trap-VEGF, having a diameter in range of 2 mcm to 70 mcm, and also relates to a method of producing a pharmaceutical composition, where said method includes: (a) spraying a solution containing water and 25 mg/ml to 50 mg/ml of trap protein-VEGF by dispersing the trap-VEGF protein solution and drying it by means of spray drying to form micro-milled protein particles, where the spray dryer inlet temperature is set at the temperature above the water boiling point, and outlet temperature is set at temperature below water boiling point and above ambient temperature, and wherein the therapeutic protein solution is pumped into the spray drier at rate of 2 ml/min to 15 ml/min; and (b) suspending the micronized protein particles in an organic solution containing a biodegradable polymer in concentration of 100 mg/ml to 300 mg/ml and an organic solvent, where the polymer is polyorthoester (POE) or ethylcellulose (EC); and (c) spray drying suspension (b) at a temperature higher than the boiling point of water to form said pharmaceutical composition, wherein the microparticles in the prolonged release pharmaceutical composition release the VEGF trap protein for at least 60 days in a physiological aqueous medium at 37 °C.
EFFECT: group of inventions provides the development of a two-step method of producing microparticles which uniformly release a therapeutically effective amount of a therapeutic protein for a long period of time.
17 cl, 7 tbl, 9 ex, 3 dwg
