Freeze-dried powder injection of pemetrexed dipotassium and preparation method thereof

Abstract

The invention provides a freeze-dried powder injection of pemetrexed dipotassium and a preparation method thereof. Specifically, the freeze-dried powder injection of pemetrexed dipotassium comprises pemetrexed dipotassium and mannitol and comprises an anti-oxidant optionally. The preparation method comprises the following steps: mixing pemetrexed dipotassium with a KOH solution at first so as to obtain a pemetrexed dipotassium solution; then uniformly mixing aqueous solutions of accessory materials and adding the obtained mixture into the pemetrexed dipotassium solution; and carrying out degerming and freeze-drying so as to obtain the freeze-dried powder injection of pemetrexed dipotassium. The prepared freeze-dried powder injection of pemetrexed dipotassium has the advantages of good stability, low moisture content, good redissolvability, low impurity content and controllable quality. The preparation method is simple and applicable to industrial production.

Description

technical field [0001] The invention relates to a freeze-dried powder injection of medicine, in particular to a freeze-dried freeze-dried powder injection of pemetrexed dipotassium and a preparation method thereof. Background technique [0002] Pemetrexed dioic acid and its derivatives, as multi-target folate antagonists, can potently inhibit multiple folate-dependent enzymes, including thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycine Amide ribonucleotide formyltransferase (GARFT), etc., have excellent antitumor activity. At present, its disodium salt, Pemetrexeddisodium, has been listed in the United States, the European Union, Canada, China, Japan and other countries, and is used for the first-line treatment of malignant pleural mesothelioma and the first-line and second-line treatment of non-small cell lung cancer. [0003] Pemetrexed diacid, CASNo.137281-23-3, the structural formula is as follows: [0004] [0005] Pemetrexed, its related compou...

AI Technical Summary

Problems solved by technology

The technical problems it solves are: the stability of pemetrexed disodium is relatively poor, it is easy to degrade under high temperature, oxidation and light conditions, and produces impurities that may cause toxic and side effects, the stability of the freeze-dried preparation is poor, and the compatible solution cannot be used in clinical use. Leave it for a long time

However, the 2.5 hydrate is unstable. Although the stability of the 3 hydrate is better than the former, it is difficult to control the amount of crystal water when drying, and 2.5 hydrate may appear.

The quality of the 7 hydrate is stable, but it is very easy to lose part of the crystallization water when stored under high temperature, low humidity or vacuum conditions, and the drying process of the hydrate also increases the process of treating with wet nitrogen flow and corresponding equipment, increasing cost of production

[0012] There are few reports in the prior art that pemetrexed dipotassium is used to prepare lyophilized formulations. The inventors have unexpectedly found that lyophilized formulations containing pemetrexed dipotassium have significant stability

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