METHOD FOR PRODUCING COVALENT CONJUGATE OF POLYETHYLENEGLYCOL WITH INTERFERON AND METHOD OF PRODUCING ACTIVATED PEG-AGENT

摘要

The invention relates to a method for producing a covalent conjugate of polyethyleneglycol with interferon characterized in that: a) free hydroxyl group of monomethoxypolyethyleneglycol is acidated by halogenhydride of nitrobenzoic acid in halogenated organic solvant in the presence of organic base, b) a nitro group of obtained metoxypolyethyleneglycol esterof nitrobenzoic acid is recovered by d-element salt of 4-th period of IV-VI group in low degree in water or water-organic medium with pH from 1.0 to 6.5 or in a medium of polar organic solvent, c) the obtained metoxypolyethyleneglycol ester of aminobenzoic acid is diazotized by nitrite of alkali or alkali-earth metal in the water or water-organic medium or by an organic nitrite in the medium of polar organic solvent with subsequent removing of nitrite excess and obtaining activated pegylated agent, d) the activated pegylated agent is introduced without isolation in the reaction of azocoupling with interferon in water or water-organic medium with pH from 7.0 to 10.0, and e) a mixture of pegylated products is separated by ion-exchange chromatography to obtain monopegylated interferon. A method is also proposed to produce activated PEG-agent. The technical result - expanding interferon spectrum and increasing circulation time in blood flow.