Novel process for preparing eptifibatide by purification

Abstract

The invention relates to a new technique for purifying and preparing eptifibatide. At present, the eptifibatide is separated, purified and produced by adopting opposite phase high pressure liquid chromatography. However, mass production is not easy to realize, and the equipment are expensive. Separation and purification are carried out by the method by applying two solvent systems which are not dissolved in each other and make epicyclic motion at high speed in a chromatographic column tube; the processing steps comprises: a. synthetic crude product of the eptifibatide is dissolved by solvent;b. the dissolved crude product of the eptifibatide is separated and purified by high-speed centrifugation separation chromatography (FCPC), and is tested by a uv detector from the distance of 230nm, so that target peak is collected by subsection; c. the collected cut fraction is tested by HPLC, wherein, the cut fraction with the purity higher than 98% is bended to be treated by the next step, andthe cut fraction with the purity lower than 98% is recycled and purified again; d. ion exchange is carried out on the cut fraction with qualified purity to remove trifluoroacetic acid (TFA), and thenthe cut fraction is transformed into acetic acid eptifibatide. The new technique has no irreversible adsorption and the advantages of no loss of sample, no pollution, high speed and high efficiency, and is suitable for mass production.

Description

technical field [0001] The invention relates to the field of medicine and chemical industry, in particular to a new process for preparing high-purity eptifibatide by using high-speed centrifugal separation chromatography (FCPC). Background technique [0002] Eptifibatide is a cyclic polypeptide containing mercaptopropionyl and six amino acid residues, the molecular formula is C 32 h 49 N 11 o 9 S 2 , is a platelet glycoprotein GPIIb / IIIa receptor antagonist, can block the platelet aggregation reaction caused by various activators, is the strongest specific platelet aggregation inhibitor known, and is mainly used to prevent myocardial oxygen supply arterial occlusion, Heart attack, unstable angina, non-Q wave myocardial infarction, sudden death caused by coronary intervention. [0003] The polypeptide has undergone multi-step synthesis, oxidation, and cracking processes, and contains a large amount of insoluble impurities, which makes the pre-treatment of the crude produ...

AI Technical Summary

Problems solved by technology

The advantage of this method is that it is simple and versatile, and is suitable for the purification of most peptides, but the disadvantage is that it is not easy to achieve large-scale production, and the production equipment is very expensive, and the investment is very large.