Dimethylaminomicheliolide fumarate crystal form C and preparation method thereof

Abstract

The invention relates to a dimethylaminomicheliolide fumarate crystal form C and a preparation method thereof, wherein X-ray powder diffraction results show that the crystal form C has characteristicpeaks at 2[theta] of 6.4+ / -0.2 DEG, 7.4+ / -0.2 DEG, 11.6+ / -0.2 DEG, 12.1+ / -0.2 DEG, 13.1+ / -0.2 DEG, 14.5+ / -0.2 DEG, 15.1+ / -0.2 DEG, 15.5+ / -0.2 DEG, 15.9+ / -0.2 DEG, 18.3+ / -0.2 DEG, 18.6+ / -0.2 DEG, 19.3+ / -0.2 DEG, 19.8+ / -0.2 DEG, 20.5+ / -0.2 DEG, 22.0+ / -0.2 DEG, 22.5+ / -0.2 DEG, 22.9+ / -0.2 DEG, 23.9+ / -0.2 DEG, 24.4+ / -0.2 DEG, 25.5+ / -0.2 DEG, 26.2+ / -0.2 DEG, 26.9+ / -0.2 DEG, 27.4+ / -0.2 DEG, 28.1+ / -0.2 DEG, 29.3+ / -0.2 DEG, 29.5+ / -0.2 DEG, 30.6+ / -0.2 DEG, 31.0+ / -0.2 DEG and 31.5+ / -0.2 DEG, wherein the characteristic peak at 6.4+ / -0.2 DEG is an initial peak, and the relative intensity of the characteristic peak at 7.4+ / -0.2 DEG is 100%. According to the invention, the preparation process is constant-temperature suspension crystal transformation preparation, the process method is simple, easy to operate and good in reproducibility, the purity of the obtained product is 99% or above, the yield is higher than 90%, the stability is good, the bulk density is high, the surface is smooth, the completerod-like crystal habit is achieved, and the method is suitable for large-scale production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical crystallization, and in particular relates to crystal form C of dimethylaminomimicrolactone fumarate and a preparation method thereof. Background technique [0002] Tumors, especially malignant tumors have caused serious harm to human health. At present, cytotoxic anticancer drugs are widely used clinically. This type of drug is like a double-edged sword. It has poor selectivity and strong toxic side effects, and it is also easy to develop drug resistance. More and more scientific studies have found that cancer stem cells are the source of most cancers' generation, development, recurrence, drug resistance and metastasis. The current clinical drug therapy and radiotherapy methods only target common cancer cells, but cannot selectively kill cancer stem cells. [0003] In recent years, the research and development of anticancer drugs has focused on finding compounds with anticancer activity...

AI Technical Summary

Problems solved by technology

[0005] Patent CN103724307B discloses crystal form A of dimethylamine mignalactone fumarate and its preparation method. Although crystal form A has many advantages over amorphous dimethylamine mignalactone fumarate, crystal form A is more The density is small, only reaching 0.270g / mL, the particle size is small, the main particle size is 35.8μm, the coalescence is serious, the angle of repose is 62°, the fluidity is poor, and it is not convenient for post-production into medicine

In addition, crystal form A is prone to crystal transformation in a solvent environment, which affects storage and transportation, and will cause many problems in later processing and handling

[0006] In order to overcome the disadvantages of the existing technology and solve the problems of current crystal form A products that are prone to crystal transformation, poor stability, poor fluidity, small particle size and easy coalescence, it is necessary to use high-throughput crystal sample screening methods to investigate different The influence of crystallization method, single solvent and mixed solvent, different temperature and stirring conditions on the crystal form of the final product, combined with various analysis and testing methods such as powder diffraction, single crystal diffraction, thermogravimetric analysis and differential scanning calorimetry analysis, the development is simple and reliable. Controlled, reproducible, safe and low-toxic process technology route, preparation and discovery of new crystal products with excellent performance, which is beneficial to subsequent drug development

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