Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Bortezomib crystal form M, and preparation method and application thereof

A technology of bortezomib and crystal form, applied in the field of bortezomib crystal form M and its preparation, can solve the problems of low stability of bortezomib crystal form, unfavorable liquid preparation preparation, weak anti-oxidation ability, etc., and achieve clarity Good and visible foreign matter, long-term storage, less increase in impurities, and fast dissolution

Inactive Publication Date: 2020-01-03
YANGZIJIANG PHARMA GROUP SHANGHAI HAINI PHARMA
View PDF15 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Form J of bortezomib solves the problems of poor solubility, weak anti-oxidation ability and unfavorable preparation of liquid preparations of bortezomib to a certain extent, but the crystallization system of form J is a mixed solvent of toluene and esters, toluene High toxicity, not conducive to green industrialized large-scale production
[0011] The bortezomib crystalline form disclosed in the above documents has low stability. From the perspective of industrial production, it is technically difficult to prepare a stable bortezomib crystalline form. Therefore, it is necessary to obtain a stable bortezomib crystalline form. Craft is very urgent and necessary

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Bortezomib crystal form M, and preparation method and application thereof
  • Bortezomib crystal form M, and preparation method and application thereof
  • Bortezomib crystal form M, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] A method for preparing bortezomib crystal form M, comprising the steps of:

[0049] Add the crude bortezomib to the test tube containing tetrahydrofuran according to the mass volume ratio of 0.3g / mL to obtain a tetrahydrofuran mixed solution, then open the test tube and place it in a beaker containing methyl tert-butyl ether and seal the beaker. The mass volume ratio of tezomib crude product to methyl tert-butyl ether is 0.04g / mL, the test tube mouth is higher than the height of methyl tert-butyl ether in the beaker, and methyl tert-butyl ether diffuses into the tetrahydrofuran mixed solution through the solvent, Crystallization at 25 ° C, that is.

Embodiment 2

[0051] A method for preparing bortezomib crystal form M, comprising the steps of:

[0052] Add the crude product of bortezomib to the test tube containing methyl tetrahydrofuran according to the mass volume ratio of 0.1g / mL to obtain a mixed solution of methyl tetrahydrofuran, then place the test tube mouth upwards and place it in a beaker filled with isopropyl ether and seal the beaker. The mass volume ratio of crude bortezomib to isopropyl ether is 0.02g / mL, the test tube mouth is higher than the height of the isopropyl ether in the beaker, the isopropyl ether diffuses into the mixed solution of methyl tetrahydrofuran through the solvent, and crystallizes at -10°C , that is.

Embodiment 3

[0054] A method for preparing bortezomib crystal form M, comprising the steps of:

[0055] The crude product of bortezomib was added into a three-necked flask filled with tetrahydrofuran under nitrogen protection according to the mass volume ratio of 0.2g / mL, and methyl tert-butyl ether was slowly added under stirring until the solid was precipitated and dissolved in a short while, and 3% (relative to bortezomib (mass fraction of rice crude product) seed crystal M (prepared by Example 1) and continue to stir, after obvious solid precipitation, continue to add methyl tert-butyl ether to the mass of bortezomib crude product and methyl tert-butyl ether The volume ratio is 0.04g / mL. Cool down to 15°C and stir for 4 hours, then filter, and wash the filter cake with a mixture of methyl tert-butyl ether / tetrahydrofuran (volume ratio 5:1) to obtain the obtained product.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to the technical field of pharmaceutical chemistry, in particular to a bortezomib crystal form M, and a preparation method and application thereof. The X-ray powder diffraction pattern of the crystal form M has characteristic peaks at positions of 2theta+ / -0.2 degrees, wherein the values of the 2theta are 4.4, 6.2, 8.6, 9.1, 10.1, 11.8, 12.4, 14.5, 18.1, 19.7, 20.9 and 21.9.The crystal form M has the advantages of high stability, simple preparation, low cost and high purity.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a crystal form M of bortezomib and a preparation method and application thereof. Background technique [0002] Bortezomib, formerly known as PS-341 (Velcade, Millennium Pharmaceuticals, Inc, Cambridge, MA) is a dipeptidyl boronic acid compound, white or off-white lump or powder, chemical name [(1R)-3 -Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinecarboxy)amino]propyl]amino]butyl]boronic acid with the formula C 19 h 25 BN 4 o 4 , the structural formula is as shown in formula I: [0003] [0004] Multiple myeloma (MM) is a malignant plasma cell disease in which tumor cells originate from plasma cells in the bone marrow, which are cells that develop to the final functional stage of B lymphocytes. Therefore, multiple myeloma can be classified as B lymphocyte lymphoma. Currently, WHO classifies it as a type of B-cell lymphoma called plasma cell myeloma / plasma cell tu...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02A61K31/69A61P35/00
CPCA61P35/00C07B2200/13C07F5/025
Inventor 王银虎徐赟姜锋李玲玲刘洪冀跃科赵佳慧庄卫红
Owner YANGZIJIANG PHARMA GROUP SHANGHAI HAINI PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com