A stable busulfan injection

Abstract

The invention provides a busulfan injection which is simple in prescription and stable in quality. The injection is prepared by the followings method: (1), dissolving busulfan into a mixed solvent of N, N-dimethyl acetamide and polyethylene glycol 400 in a volume ratio of (17-57):(83-43) to obtain a busulfan solution with concentration of 1mg / mL-7.5mg / mL; and (2), filtering and filling in a sterile manner, wherein in the dissolving process of the step (1), the temperature of the solution is 4 DEG C-25 DEG C, or / and inert gases are charged in an operation process until the solution is saturated. Not only is stability of the busulfan injection obtained by the preparation method disclosed by the invention improved, but also the safety of the injection after long-time storage is effectively ensured. Meanwhile, other substances or other chemical components are not introduced in the preparation process, so that the medication safety is ensured, and the drug cost is also lowered.

Description

technical field [0001] The invention relates to a preparation method of busulfan injection and the busulfan injection prepared by the method, belonging to the field of pharmaceutical preparations. Background technique [0002] Busulfan is a dimethylsulfonate bifunctional alkylating agent, which was first discovered in 1953. In terms of mechanism of action, busulfan is a cytotoxic antineoplastic drug. After entering the human body, its sulfonate group will undergo alkylation with guanine in tumor cells, interfering with the formation of tumor cell genetic material. , thereby inhibiting the growth of tumor cells. Busulfan is mainly suitable for proliferative diseases of blood and bone marrow, especially for chronic myeloid leukemia, essential thrombocythemia, polycythemia vera, primary myelofibrosis and other diseases. However, due to the poor solubility of busulfan, especially the worst in water solubility, it is difficult to absorb after oral administration, and the dose r...

AI Technical Summary

Problems solved by technology

However, there are ester bonds that are easily hydrolyzed in the structural formula of busulfan, and are easily degraded by water to produce toxic tetrahydrofuran and methanesulfonic acid, which not only reduces the curative effect of the drug, but also increases the toxicity and irritation of the drug. The clinical application of Busulfan has buried a great hidden danger, so the water content in the preparation process of Busulfan must be strictly controlled

However, the solubilizer polyethylene glycol 400 in the existing injections is extremely easy to absorb water, and the inevitable environmental exposure in the production process will cause a large amount of water absorption, and polyethylene glycol 400, N, N-dimethylacetamide Or the trace amount of moisture carried by the active ingredients of the drug itself is enough to affect the stability of the product

At the same time, the busulfan injection prepared by the existing method cannot be stored for a long time, which not only brings great inconvenience to clinical medication, increases the risk of use, but also greatly increases the production cost of the drug

Because, when the produced medicine cannot be sold and used in a short period of time, it will quickly deteriorate and cannot be used any longer, and can only be destroyed, which will lead to a large amount of waste of medicine and further increase the cost

[0004] The inventor’s previous Chinese patent application (CN102151257A) disclosed a busulfan injection, which improved the stability of the busulfan injection by adding an organic acid or its alkali metal or alkaline earth metal salt as a stabilizer, but , due to the addition of chemical stabilizers, the busulfan injection is inconsistent with the existing drug standards, resulting in a long research and improvement process for the preparation to be approved for clinical use

[0005] So far, no studies and reports have been found on busulfan injections that meet the current busulfan drug standards and have drug safety and long-term storage stability

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