Preparation method of cetrorelix

Abstract

The invention relates to a preparation method of cetrorelix, specifically to a synthesis method combining solid and liquid phases. According to the order of cetrorelix sequence from C terminal to N terminal, 1-9 fragments are connected one by one by the solid-phase synthesis method under the action of a coupling reagent, and then the 1-9 fragments undergo fully-protected cut and then are subjectedto fragment condensation with DAla-NH2.HCl in a liquid phase so as to obtain fully-protected cetrorelix; the cetrorelix is cut by a lysis buffer; a cutting fluid is precipitated by ice ether to obtain cetrorelix crude peptide; and finally the cetrorelix crude peptide is purified by reverse-phase high-performance liquid chromatography to obtain a cetrorelix finished product. The preparation methodis simple, is suitable for industrial production, and has high production efficiency.

Description

technical field [0001] The invention belongs to the technical field of polypeptide drug preparation methods, in particular to a preparation method of cetrorelix, which specifically adopts a solid-liquid phase synthesis method. Background technique [0002] Cetrorelix (trade name Cetrotide) is a potent progesterone-releasing hormone-releasing hormone (LH-RH) receptor antagonist, which can control the stimulation of the ovary, prevent premature discharge of immature follicles, and help conception. And can be used for the treatment of breast cancer and gynecological cancer, endometriosis, precocious puberty, uterine fibroids, ovarian androgen excess and premenstrual syndrome. [0003] Chinese name: Sicurelix [0004] English name: Cetrorelix acetate [0005] Sequence: Ac-D2Nal 1 -D4Cpa 2 -D3Pal 3 -Ser 4 -Tyr 5 -DCit 6 -Leu 7 -Arg 8 -Pro 9 -DAla 10 -NH 2 [0006] Molecular formula: C 70 h 92 ClN 17 o 14 [0007] Molecular weight:: 1431.06 [0008] Among the c...

AI Technical Summary

Problems solved by technology

However, after this method, the solid-phase synthesis of Fragment B uses expensive Sieber resin for solid-phase synthesis, and the cost is relatively large.

And Fragment B has an extra full-protection cutting step, resulting in many and complicated steps in the overall process, which has a greater risk in large-scale production

[0016] The method of the above-mentioned patent has problems such as complex method, unsuitability for industrial production, low production efficiency, etc.

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