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Method for preparing carfilzomib amorphous crystal

A carfilzomib and amorphous technology, applied in the direction of peptides, etc., can solve the problems of affecting the stability of substances, difficult to remove water, etc., and achieve the effect of easy removal, low moisture content, and favorable industrial production

Inactive Publication Date: 2015-03-11
CHONGQING TAIHAO PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this method for preparing carfilzomib amorphous crystals uses water, which is difficult to remove during the drying process, which will affect the stability of the substance

Method used

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  • Method for preparing carfilzomib amorphous crystal
  • Method for preparing carfilzomib amorphous crystal
  • Method for preparing carfilzomib amorphous crystal

Examples

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preparation example Construction

[0024] The invention provides a kind of preparation method of carfilzomib amorphous crystal, comprises the following steps:

[0025] Carfilzomib is dissolved in an organic solvent to obtain a carfilzomib solution;

[0026] Concentrating the carfilzomib solution to obtain amorphous carfilzomib.

[0027] The preparation method of the amorphous crystal provided by the present invention uses an organic solvent without adding water, the organic solvent is easy to remove during the concentration process, no residue will be generated in the product, and the moisture content is low, and no crystal water will be formed, so that the obtained Carfilzomib amorphous crystal has high stability. And the preparation method of carfilzomib amorphous crystal provided by the present invention is after dissolving carfilzomib, directly concentrates and dries the obtained carfilzomib solution, without going through the process of crystal growth and crystallization, the obtained carfilzomib The non...

Embodiment 1

[0064]1g of carfilzomib crude product is dissolved in the mixed solution of ethyl acetate and n-hexane with a volume ratio of 2:1, and the obtained concentration of carfilzomib crude product solution of 0.5g / mL is added to a silica gel column, and the silica gel The particle size of the silica gel filled in the column is 200 mesh to 250 mesh, the control parameter of the wet packing column is 15g carfilzomib / kg silica gel, and the mixed solution of ethyl acetate and n-hexane with a volume ratio of 2:1 is used as the mobile phase. Carry out column chromatography separation, the flow velocity of mobile phase in the column chromatography separation is 5mL / min, track with HPLC, the parameter that HPLC detects is:

[0065] The chromatographic column is Agilent Extend-C18 150mm×4.6mm, 3.5μm; the column temperature is 30°C; the injection volume is 10μL; the flow rate is 1mL / min; the mobile phase includes solution A and solution B, and the molar concentration of solution A is 0.02mol / m...

Embodiment 2

[0079] Under the condition of stirring, 1g of carfilzomib crude product was dissolved in 15mL of methanol, filtered to remove insoluble impurities, the filtrate was concentrated to dryness under reduced pressure at a vacuum of 0.1 and a temperature of 40°C, and then Under the conditions of 0.1 and a temperature of 50° C., dry under reduced pressure for 12 hours to obtain carfilzomib crystals.

[0080] The present invention adopts X-powder diffraction method to detect the carfilzomib crystal obtained, and the result is as follows: image 3 as shown, image 3 For the XRPD spectrum of the carfilzomib crystals of Example 2 of the present invention, by image 3 It can be seen that the carfilzomib crystals obtained in this example are amorphous carfilzomib crystals.

[0081] The water content of the amorphous carfilzomib crystal obtained by the detection of the present invention, the results show that the water content of the amorphous carfilzomib crystal obtained by the method of...

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Abstract

The invention provides a method for preparing a carfilzomib amorphous crystal. The method comprises the following steps: dissolving carfilzomib in an organic solvent to obtain a carfilzomib solution; concentrating the carfilzomib solution to obtain the carfilzomib amorphous crystal. The method has the advantages that as the solvent is organic, no water is needed, and the organic solvent is easy to remove during concentration, no residual can be generated in the product, the moisture content is extremely low, no crystal water is formed, and the obtained carfilzomib amorphous crystal is relatively high in stability. The carfilzomib amorphous crystal is prepared by dissolving carfilzomib and directly concentrating and drying the carfilzomib solution, that is, the processes of crystal growth and devitrification are not avoided, so that the obtained carfilzomib crystal is amorphous. Therefore, the method is simple, high in operability, and suitable for large-scale industrialized production.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a method for preparing an amorphous carfilzomib crystal. Background technique [0002] Carfilzomib (Carfilzomib), the chemical name is (2S)-N-((S)-1-((S)-4-methyl-1-((R)-2-methyloxirane- 2-yl)-1-oxopentan-2-ylcarbamoyl)-2-phenethyl)-2–((S)-2-(2-morpholineacetamido)-4-phenyl Butyramide)-4-methylpentanamide, the trade name is Kyprolis, and the molecular formula is C 40 h 57 N 5 o 7 , has the structure shown in formula I: [0003] [0004] Carfilzomib was first produced by Onyx Pharmaceuticals as carfilzomib injection freeze-dried powder, which was approved by the U.S. Food and Drug Administration (FD) on July 20, 2012. Multiple myeloma patients treated with 2 drugs, including bortezomib and immunomodulators. The approval of carfilzomib provides a treatment option for patients with multiple myeloma who have relapsed after treatment with current therapies. In t...

Claims

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Application Information

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IPC IPC(8): C07K7/06C07K1/30
Inventor 李靖姚全兴喻威吴进
Owner CHONGQING TAIHAO PHARM CO LTD
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