A kind of pemetrexed disodium freeze-dried powder for injection

Abstract

The invention provides a pemetrexed disodium lyophilized powder injection for injection, and belongs to the field of medicine pharmacy. The pemetrexed disodium lyophilized powder injection is preparedfrom pemetrexed disodium, mannitol, hydroxypropyl-beta-cyclodextrin, EDTA (Ethylene Diamine Tetraacetic Acid), tertiary butanol and a pH modifier. A method provided by the invention comprises the steps of adding the hydroxypropyl-beta-cyclodextrin into water for injection, adding a prescription dosage of the mannitol and pemetrexed disodium, then adjusting to an appropriate pH value, filling withan ampoule, and pull-sealing the ampoule after freeze-drying, wherein during dispensing and freeze-drying processes, an inert gas is introduced for protecting. The pemetrexed disodium freeze-dried powder injection for injection prepared through the method has the advantages of low water content, good appearance, fewer related substances, applicability for long-term storage, and the like.

Description

technical field [0001] The invention belongs to the field of medicine and pharmacy, and in particular relates to a freeze-dried powder injection of pemetrexed disodium for injection. Background technique [0002] The chemical name of pemetrexed disodium is N-(4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrole[2,3 -d]pyrimidin-5-yl)ethyl]benzoyl)-L-glutamate disodium, which is a new anti-tumor drug acting on multiple targets in the folic acid metabolism process. Preclinical and clinical studies have confirmed that it has clear anti-multiple solid tumor activity, including lung cancer, breast cancer, pancreatic cancer, ovarian cancer, etc., and is particularly effective for the treatment of malignant pleural mesothelioma (MPM). [0003] Pemetrexed is an antifolate preparation with a pyrrolic pyrimidine group in its structure. It can inhibit the growth of tumors by destroying the normal metabolic process dependent on folic acid in cells and inhibiting cell replication. In vitro studi...

AI Technical Summary

Problems solved by technology

[0005] CN101411710A discloses a pemetrexed disodium freeze-dried powder injection and a preparation method thereof. The pemetrexed disodium freeze-dried powder injection is composed of pemetrexed disodium, mannitol and sodium sulfite, and sodium sulfite is a commonly used antioxidant It has strong chemical activity and can undergo addition reaction with some aldehydes and ketones, and will have a certain impact on the efficacy of the main drug. In addition, because the human body has extremely high requirements for freeze-dried powder injection, and this There are many types of excipients in the freeze-dried powder injection, which not only increases the types and contents of impurities in the freeze-dried powder injection, but also increases the risk caused by impurities in the excipients. The impurity content of the freeze-dried powder injection is 0.72% to 0.85% %; Moreover, during the freeze-drying process of the freeze-dried powder, first cool the product to -40°C, continue to freeze for 2-4 hours, vacuumize, and then raise the temperature to 35°C at a rate of 2-4°C per hour. ℃, the freeze-drying process is rough, and the moisture content of the finished product after freeze-drying is high. The moisture content of the freeze-dried powder injection is 4.8% to 5.8%. In addition, during the drying process, the heating rate is too slow, and the energy required for production Excessive consumption, low economic benefit

Contains two pH adjusters, complicated operation

[0008] CN102525955A discloses a preparation process of pemetrexed disodium for injection. The prescription is 200 g of pemetrexed disodium, 200 g of mannitol, an appropriate amount of hydrochloric acid or sodium hydroxide, and 10 L of water for injection. After preparing the liquid medicine, it is freeze-dried However, the improvement effect of this technology on the problem of poor stability of the main drug is not obvious

[0009] Pemetrexed disodium has poor stability and is prone to degradation under high temperature, oxidation and light conditions, resulting in impurities that may cause toxic and side effects

And during the storage process, it was found that its moisture and related substances continued to increase, and the clarity after reconstitution was not good.

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