Artesunate preparation for injection, and application thereof

Abstract

The invention discloses an artesunate preparation for injection. The artesunate preparation for injection includes sterile artesunate powder and an auxiliary material pH regulator powder for injection. The pH regulator for injection is one of disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium hydroxide and potassium hydroxide, or a mixture containing more of above substances according to an arbitrary ratio, and preferably one of the disodium hydrogen phosphate and dipotassium hydrogen phosphate or a mixture containing the disodium hydrogen phosphate and dipotassium hydrogen phosphate according to an arbitrary ratio. A molar ratio of the sterile artesunate to the pH regulator is 1:1 to 1:6, and preferably 1:1.0 to1:4.0. The above composition has obviously better solubility, solution stability and solid preparation stability than commercially available artesunate for injection, and is suitable for being clinically used.

Description

technical field [0001] The invention relates to an artesunate preparation for injection, its preparation and application, and belongs to the technical field of medicine preparation. Background technique [0002] Artemisinin, also known as artemisinin, is a sesquiterpene lactone drug with peroxy groups extracted from the stems and leaves of the plant Artemisia annua. It is widely used as a drug for treating malaria, mainly for vivax malaria and falciparum malaria. Symptom control, and treatment of chloroquine-resistant strains. Artemisinin-based combination therapy has been widely used in the treatment of malaria for nearly half a century, and has played a huge role in the human war against malaria. Artemisinin has disadvantages such as high dosage, high recurrence rate, and low solubility in water and oil. Scientists and pharmaceutical companies have discovered artemisinin derivatives (dihydroartemisinin, artemether, artemisinin, etc.) in the structural modification of arte...

AI Technical Summary

Problems solved by technology

[0009] (1) When 60mg of artesunate powder for injection was dissolved by adding 1ml of 5% sodium bicarbonate aqueous solution and shaken to dissolve, a large amount of carbon dioxide gas was generated, which made the artesunate powder adhere to the bottle wall, making it difficult to judge whether it was dissolved, and It needs to be shaken for 4-5 minutes to be basically dissolved, which takes time to dissolve; and the carbon dioxide gas generated during the shaking process may flush the cork, and the liquid in the bottle will come out, posing a safety hazard;

[0010] (2) Due to the defect of its preparation method, it is extremely inconvenient to use artesunate for injection when it is used to rescue critically ill patients;

If the shaking time is too long in clinical use without dissolving, part of the artesunate may have been decomposed into dihydroartemisinin and precipitated, which can no longer be used;

[0012] (4) Commercially available artesunate for injection is packaged in a glass bottle containing 60 mg artesunate sterile powder and an ampoule containing a special solvent (5% sodium bicarbonate aqueous solution), which is complicated and inconvenient to use

While the disclosed composition is superior in solubility to commercially available formulations, no definite improvement in stability is disclosed

Moreover, the organic base disclosed in this invention is not a commonly used excipient for injection preparations. Under the optimal ratio of artesunate / excipient disclosed in the invention (1:1-6), the toxicity data of the excipient is unknown, and its clinical use is relatively risky. Big

[0017] Although the above-mentioned reports have made many improvements to artesunate preparations for injection, there is no artesunate preparation for injection that is more suitable for clinical use, easy to dissolve, and has good stability.

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