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Lenalidomide crystal and preparation method thereof

A technology of lenalidomide and crystal, applied in the field of lenalidomide crystal and its preparation, can solve the problems of unmentioned solubility and improvement, and achieve easy operation and implementation, good solubility, and crystal stability. Good results

Inactive Publication Date: 2018-06-22
ZHEJIANG ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Patent WO 2009114601, Invention Patent Application Specification CN201410169124.2, CN201410290468.9, CN201410822842.5 and other documents disclose other crystal forms and amorphous forms of lenalidomide, all of which have certain advantages, but none mention solubility promotion

Method used

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  • Lenalidomide crystal and preparation method thereof
  • Lenalidomide crystal and preparation method thereof
  • Lenalidomide crystal and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1 (preparation of new crystal form of lenalidomide)

[0038] Add 1.1g of commercially available lenalidomide (Wuhan Yuancheng Gongchuang Technology Co., Ltd., batch number: 20160901) into a 250mL flask, add 120mL of anhydrous methanol, stir and heat to reflux, heat filter after dissolving, and place the filtrate in The crystallization was naturally cooled at room temperature of 30°C, the solid was collected by filtration, and dried under reduced pressure for two days at a temperature of 30°C, with a yield of 95.6%.

[0039] The obtained crystal sample is subjected to X-ray powder diffraction test, and the spectrum is shown in figure 1 (Using Bruker D8ADVANCE model X-ray powder diffractometer of German Bruker company to analyze the crystal phase of the sample, radiation source Cu Kα, scanning method: step scanning; primary Twin opitcs: 0.5° divergence; secondary Twin opitcs: fixed mm, 5.8 mm; scanning range: 3°~40°; scanning step length: 0.02°; dwell time of ...

Embodiment 2

[0043] Embodiment 2 (preparation of new crystal form of lenalidomide)

[0044] Add 1.1g of commercially available lenalidomide into a 250mL flask, add 120mL of anhydrous methanol, stir and heat to reflux, dissolve and filter hot, place the filtrate to cool at 40 degrees Celsius, filter and collect the precipitated solid, and depressurize After drying for two days, the yield was 89.1%. The X-ray powder diffraction, DSC, and TGA spectra of the crystal are basically consistent with those of Example 1.

Embodiment 3

[0045] Embodiment 3 (solubility test)

[0046] Test group: the new crystal form of lenalidomide prepared by the inventive method;

[0047] Control group: lenalidomide crystal form B prepared by referring to the method disclosed in the existing literature (CN1871003, US20050096351).

[0048] Instruments and reagents:

[0049] High performance liquid chromatography: SHIMADZU (SPD-20A)

[0050] Electronic balance: SARTORIUS (BP211D)

[0051] Oscillator: Incubator Shakers (HZ-9211KB)

[0052] purified water

[0053] Methanol (analytical pure)

[0054] Chromatographic conditions:

[0055] Chromatographic column: DikamaTechndogiesC18 (250*4.6mm, 4.6um)

[0056] Mobile phase: 0.05% formic acid aqueous solution: acetonitrile solution = 20:80

[0057] Detection wavelength: 254nm; flow rate: 1.0ml / min; column temperature: 35°C

[0058] Under the above-mentioned chromatographic conditions, the retention times of lenalidomide series compounds are shown in Table 2:

[0059] Table...

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Abstract

The invention discloses a stable lenalidomide crystal (new crystal form Z) and a preparation method thereof. The prepared lenalidomide new crystal form Z has good solubility and good crystal form stability. According to the stable lenalidomide crystal (new crystal form Z), Cu-K alpha radiation is used, and X-ray powder diffraction expressed in 2 theta angle has distinctive diffraction peaks at 7.9plus or minus 0.2 degrees, 14.4 plus or minus 0.2 degrees, 15.8 plus or minus 0.2 degrees, 17.7 plus or minus 0.2 degrees, 20.6 plus or minus 0.2 degrees, 23.8 plus or minus 0.2 degrees and 31.9 plusor minus 0.2 degrees. The preparation method of the lenalidomide crystal (new crystal form Z) comprises the steps: dissolving lenalidomide in methanol, stirring and heating to reflux, dissolving andthen filtering by hot filtration to obtain a filtrate; and subjecting the filtrate to natural cooling at room temperature for crystallization, filtering and collecting solid, and drying under reducedpressure at room temperature to obtain the lenalidomide crystal.

Description

technical field [0001] The invention relates to the technical field of lenalidomide crystals, in particular to a lenalidomide crystal (new crystal form Z) and a preparation method thereof. Background technique [0002] Lenalidomide (structural formula shown in formula I) is used to treat various diseases, including cancer, inflammation and autoimmune system diseases. [0003] [0004] Lenalidomide affects multiple biological pathways in cells, including multiple myeloma, myelodysplastic syndrome, chronic lymphocytic leukemia, and solid tumors. It is a new generation derivative of thalidomide, but it has not been found to have mutagenic toxicity, and its drug effect is 100 times stronger than that of thalidomide. According to the results of phase III clinical trials, lenalidomide is currently the most effective drug for the treatment of multiple myeloma, and more than half of the patients can prolong their survival time by more than 3 years after taking the drug. In addi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/04
CPCC07B2200/13C07D401/04
Inventor 章迟啸王尊元张智敏梁美好黄文海马臻沈正荣
Owner ZHEJIANG ACAD OF MEDICAL SCI
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