Injection preparation containing camptothecin analogue, and injection, preparation and application thereof

Abstract

The invention relates to an injection preparation containing camptothecin analogue, and the injection, the preparation and the application thereof. The injection preparation comprises a solid part and a liquid part which are separately and independently packaged, wherein the solid part adopts a freeze-dried powder; the freeze-dried powder comprises an active component and one or more pharmaceutically acceptable excipients; the active component adopts the camptothecin analogue or pharmaceutically acceptable salt; the liquid part at least comprises the following components: a solubilizer and water for injection; the camptothecin analogue has the structure as shown in the specification.

Description

technical field [0001] The invention relates to the field of medicine, in particular to an injection preparation containing a camptothecin derivative, its injection solution, preparation and application. Background technique [0002] Camptothecin, a cytotoxin that inhibits topoisomerase I, an enzyme essential for DNA synthesis, was first isolated from the leaves of Camptotheca acuminata. The α-hydroxylactone on the E ring in the chemical structure of camptothecin has two forms of open ring and closed ring. The closed ring form of camptothecin drugs has poor water solubility and high anticancer activity. The open-ring form has low activity, high toxicity, and serious adverse reactions in clinical trials. [0003] Over the years, scientists from various countries have synthesized hundreds of camptothecin derivatives for screening, and many compounds have entered clinical research. So far, only four derivatives have been successfully marketed. Due to insufficient development ...

AI Technical Summary

Problems solved by technology

A significant shortcoming of this technical solution is that the obtained product is stored in a closed loop and used in an open loop.

In addition, during the implementation of the technical solution, the active ingredient has a chemical transformation process of first ring opening, then ring closing, and finally ring opening. These processes will bring the following problems: (1) the efficiency of chemical transformation affects the implementation effect; (2) by The pH-controlled chemical transformation is not specific in the presence of other active groups (such as 14-amino), and the complexity of the chemical transformation will lead to an increase in the type and total amount of impurities; (3) the ring-closing reaction in the preparation process can cause Solubility reduction and precipitation, generation of insoluble solid material is very unfavorable for intravenous injection

In order to solve the problems of stability and the like, the present invention adopts a brand-new design idea, overcomes the problems of low solubility and poor stability of the active ingredient, and makes up for the deficiencies in the existing insoluble camptothecin derivative drug delivery system

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