Composition containing antifungal drug and lactate buffering agent

Abstract

The invention relates to a drug composition, containing caspofungin or pharmaceutically acceptable salts thereof, and a lactate buffering agent in a pharmaceutically acceptable amount. By addition of the lactate buffering agent, the composition greatly decreases generation of caspofungin degradation product, greatly raises stability of caspofungin, and is convenient for preservation and clinic usage, thereby raising usage security of caspofungin.

Description

technical field [0001] The present invention relates to a pharmaceutical composition for treating and / or preventing fungal infection, which comprises caspofungin or a pharmaceutically acceptable salt thereof and lactate buffer. Background technique [0002] Caspofungin has the following structural formula, [0003] [0004] It belongs to the antifungal drug of azacyclic hexapeptide of echinocandins, and its preparation method has been described and disclosed in US5378804 (ZL94191487.9), US5552521, US595230, US6136783, CN101305018A, CN101792486A. Caspofungin inhibits the synthesis of β-(1,3)-D-glucan, an essential component of the cell walls of many filamentous fungi and yeasts, whereas β-( 1,3)-D-glucan. Caspofungin has antibacterial activity against many species of pathogenic Aspergillus and Candida fungi and is effective against fungi resistant to amphotericin B and fluconazole. [0005] Caspofungin compounds are inherently highly unstable and can degrade in various ...

AI Technical Summary

Problems solved by technology

[0006] Patent ZL97195514.X or US6136783 discloses the medicinal composition of caspofungin containing acetate buffer, it is believed that the storage period of the composition is prolonged due to the use of acetate buffer, and the freeze-dried product is more than The buffering agent using other salts is more stable and contains less unwanted degradation products, but it only discloses some embodiment schemes without giving clear data on degradation products. After the inventor's test, the buffer containing acetate The pharmaceutical composition of the dose is not stable enough

[0007] WO2009002481A1 discloses the use of non-reducing sugars, such as trehalose, to prepare freeze-dried compositions. It is believed that the use of non-reducing sugars can increase the glass transition temperature (Tg) of the freeze-dried powder and improve the stability of the freeze-dried composition against heat property, it still uses acetate buffer, and it is still acetate buffer that plays a stabilizing role. The whole invention does not deviate from the invention scope of patent ZL97195514.X or US6136783, and the pharmaceutical composition is not stable enough

[0008] Patent application CN101516397A or WO2008012310A1 discloses that a very small amount of acetic acid can be used as a pH regulator to prepare a caspofungin pharmaceutical composition with good stability. The acetate buffer system is still used, and the invention is still in patent ZL97195514.X or The scope of the invention of US6136783, and the pharmaceutical composition is more unstable than the pharmaceutical composition disclosed in the patent ZL97195514.X or US6136783, and cannot be used in practice

[0009] CN102166186A claims to have made a caspofungin composition containing sulfate, citrate, phosphate, or lactate, but after investigation, the experimental data in this document are far from the actual situation, caspofungin The net is extremely unstable, and the freeze-dried powder needs to be stored at 2-8°C, and a large amount of impurities will be produced quickly after reconstitution and contact with water. Afterwards, it also has good stability, which is contradictory to the actual situation, so those skilled in the art will not think that the application is completing the preparation of the caspofungin composition after reading the description of the application

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