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According to the method disclosed by the invention, the crude semaglutide is prepared by carrying out liquid-phase one-step reaction on two segments of fragment peptides in a liquid phase, in the final liquid chromatography purification step, impurities are not defective peptides lacking one or more amino acids, but are uncondensed partial fragments, the purification difficulty is not caused, in addition, the uncondensed partial peptide fragments can be recycled, and the cost is saved

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