Stable ast-3424 injection preparation and preparation method

Abstract

A stable AST-3424 injection preparation, which is a solution containing 0.1-200 mg / ml or 1-200 mg / ml of AST-3424 raw material drug, and the solvent of the solution contains C2-C8 monohydric alcohol. The preparation method comprises the following operations: dissolving and preparing the AST-3424 bulk drug and part of the prescribed amount of ethanol for the first time; adding the prescribed amount of propylene glycol for the second dissolving and preparing; adding the remaining prescribed amount of ethanol for mixing and dissolving Promptly obtain the solution containing the AST-3424 crude drug of 1-200mg / ml. AST‑3424 injection for injection, its solvent is water, or glucose solution, ethanol, propylene glycol solute is made up of AST‑3424 bulk drug, adjusting isotonicity reagent and pH regulator, the concentration of the AST‑3424 bulk drug of this injection is 0.001-1.000mg / ml, the pH of the injection is 6.8-10.5, and it is an isotonic solution.

Description

technical field [0001] The present invention relates to the research and development of injections of compounds disclosed in the patent application PCT / US2016 / 021581, publication number WO2016145092A1, corresponding to Chinese application number 2016800150788, publication number CN107530556A, and belongs to the field of preparation research and development of cancer treatment compounds. Background technique [0002] The DNA alkylation cancer treatment drug AST-3424 developed by our company targets the overexpressed aldehyde and ketone reductase 1C3 (AKR1C3) (see patent application: DNA alkylating agent, corresponding to PCT application number PCT / US2016 / 021581, publication number WO2016 / 145092, corresponding to the Chinese application number 2016800150788, the compound TH2870 disclosed in the publication number CN107530556A; (R)- and (S)-1-(3-(3-N,N-dimethylaminocarbonyl)phenoxy- 4-Nitrophenyl)-1-ethyl-N,N'-bis(ethylenyl) phosphoramidate, composition and its use and preparat...

AI Technical Summary

Problems solved by technology

[0006] During the synthesis and preparation process, it was found that the substance was a light yellow liquid, and there were many difficulties in storage, transportation, and preparation: due to the amide and phosphate structures, it was inconvenient to develop tablets and oral liquid dosage forms for oral administration. However, the research and development team initially The test found that the conventional injection with water as the solvent was not stable enough to meet the requirements of subsequent multi-center, multi-sample long-term clinical trials and commercial production and sales

Images