Preparation method for carbetocin

Abstract

The invention discloses a preparation method for carbetocin. The preparation method comprises the following steps: subjecting swelled, deprotected and washed amino resin to reacting with an activated protected amino acid solution in a constant-temperature vibrator, carrying out successive introduction into protected amino acids corresponding to first-to-eighth amino acids accounting from the resin and into butyric acid at the tail end of N; subjecting prepared carbetocin precursor peptide 1-amino resin to deprotection, carrying out washing, then carrying out drying until the dried carbetocin precursor peptide 1-amino resin is of a granular shape, adding a cutting reagent, and carrying out a cutting reaction and settling; dissolving a carbetocin precursor peptide II in a solvent, removing impurities by adopting a reversed phase highly-efficient liquid chromatography method, and carrying out liquid-phase cyclizing so as to obtain a crude carbetocin peptide III; and subjecting the crude carbetocin peptide III to purifying and freeze-drying so as to obtain a pure carbetocin polypeptide. The preparation method provided by the invention utilizes an Fmoc solid-phase synthetic principle to develop a solid-phase synthetic technology; and through process optimization, the yield of crude carbetocin is up to 90% or above, so the yield of carbetocin is greatly improved.

Description

technical field [0001] The invention belongs to the technical field of polypeptide drug preparation methods, in particular to a preparation method of carbetocin. Background technique [0002] Chinese name: carbetocin [0003] English name: Carbetocin [0004] Structural formula: [0005] [0006] Molecular formula: C 45 h 69 N 11 o 12 S [0007] Peptide traits: white loose powder [0008] Carbetocin Acetate is a synthetic long-acting oxytocin octapeptide analogue with agonist properties, and its clinical and pharmacological properties are similar to those of naturally occurring oxytocin. Carbetocin binds to the oxytocin receptor of uterine smooth muscle, causing rhythmic contraction of the uterus, increasing its frequency and increasing uterine tension on the basis of the original contraction. Oxytocin receptor levels in the uterus are low in the non-pregnant state, increase during pregnancy, and peak at delivery. Carbetocin therefore has no effect on the non-...

AI Technical Summary

Problems solved by technology

[0009] Most of the existing carbetocin preparation methods are solid-liquid synthesis methods, and the synthesis cycle is long, the production cost is high, and the product activity is low, which is not conducive to the large-scale production of carbetocin

LiOH, NaHCO were used in the synthesis method of ES2115543 3 and DMAP raw materials, which will lead to many impurities, reducing the purity and use effect of the product

Adopted Cys (Alloc) raw material in the synthetic method of CN200910106889, and carry out cyclization with lithium chloride as cyclization reagent, obtain carbetocin after acidolysis, there is the problem of catalyst poisoning in this method, Cys (Alloc) in removing After Alloc protection -SH is exposed, it is very easy to poison the tetrakistriphenylphosphine palladium catalyst, which seriously affects the efficiency of the deprotection reaction

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