Post-treatment method of GnRH antagonist

Abstract

The invention discloses a post-treatment method of a GnRH antagonist. The GnRH antagonist is subjected to concentration treatment by combining a nanofiltration process with a subsequent freeze-dryingprocess. The method can improve the purity and yield of the product, simplify the steps, reduce the cost, obtain a stable product with controllable moisture, acetic acid and optical density, and is more suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a post-treatment method of GnRH antagonists. It belongs to the technical field of biomedicine. Background technique [0002] GnRH antagonists are synthetic gonadotropin-releasing hormone analogs that inhibit the proliferation and metastasis of prostate cancer by inhibiting testosterone. GnRH antagonists mainly include abarelix, cetrorelix, Nal-Glu, ganirelix, and degarelix. The post-processing method involved in the present invention mainly refers to the concentration method and freeze-drying process of the purified sample solution. The post-processing method is a very important link in the process of preparing the GnRH antagonist raw material drug, which will directly affect the quality of the active ingredient of the drug. [0003] In the prior art, the patent CN102428097 uses column concentration + vacuum rotary evaporation to concentrate the purified sample of degarelix, and then lyophilizes it. The patent CN201380028448 ...

AI Technical Summary

Problems solved by technology

[0004] Although the patent CN201380028448 mentioned three concentration methods, when the sample is concentrated by vacuum rotary evaporation, the concentration speed is slow, the efficiency is low, the concentration time is long, and the relatively high temperature of the rotary evaporation may cause the degradation of the sample, so it does not It is not suitable for large-scale industrial production; using freeze-drying to concentrate samples is not only time-consuming, but also has high requirements on the performance of the freeze dryer, and is also not suitable for industrial production; although the method of column concentration is limited to a certain extent In fact, the purpose of concentration can be achieved, but the disadvantages are also obvious. The use of organic solvents is involved in the process of column concentration, which will cause harm to human health and the natural environment. Liquid treatment also directly increases the cost of concentration

However, the method of column concentration + vacuum rotary evaporation mentioned in the patent CN102428097 is not only cumbersome, but also increases the use of organic solvents, and the concentration cost is higher

Special attention should be paid to the fact that due to the high viscosity of GnRH antagonists, the sample will undergo self-polymerization reaction during the use of the above-mentioned post-processing methods. The self-polymerization during synthesis will introduce new impurities, affect the purity of the drug, and increase the risk of patients. Although acetic acid can be depolymerized after self-polymerization occurs in the synthesis, whether the depolymerization can be completed and whether the sample is stable are also issues that need to be considered.