Method for purifying gemcitabine hydrochloride

A gemcitabine hydrochloride and purification method technology, applied in the field of compound purification, can solve the problems of product purity and yield reduction, cost increase, gemcitabine hydrochloride instability, etc.

Active Publication Date: 2014-08-13
SHANGHAI DINGYA PHARM CHEM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The weak point of this method is to directly add acetone in gemcitabine hydrochloride aqueous solution, because gemcitabine hydrochloride is very soluble in water, the existence of water can cause the reduction of product yield in the crystallization process, needs to use a large amount of acetones and just can separate out crystal simultaneously, makes Increased solvent usage leading to higher costs
Although the refining method of gemcitabine hydrochloride given in the master's thesis of Nanjing University of Science and Technology "Research on the Development of Gemcitabine Hydrochloride Raw Materials" (page 28) concentrates water, the method of concentration is to use a rotary evaporator at 60 ° C. In addition to water, gemcitabine hydrochloride is unstable at this temperature, and impurities will be produced, resulting in a reduction in product purity and yield

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Add 1 kg of crude gemcitabine hydrochloride (gemcitabine hydrochloride content 99.03%, related impurity content 0.95%) to 6L water for injection, stir until dissolved at room temperature, add 30 g of activated carbon for decolorization for 15 minutes, filter, collect the filtrate, and set the temperature of the lyophilizer to At 5°C~10°C, place the filtrate in a lyophilizer and concentrate to 720mL to obtain the gemcitabine hydrochloride concentrate; then add 1.6L acetone to the gemcitabine hydrochloride concentrate, stir overnight at room temperature, filter with a 0.22μm microporous membrane, and use 500mL of acetone was washed, and the filter cake was placed in a lyophilizer to dry to obtain 839.3g of gemcitabine hydrochloride pure product, with a yield of 84.7%. Sampled for HPLC, its purity was 99.97% (related impurity content 0.014%).

Embodiment 2

[0017] Add 1 kg of gemcitabine hydrochloride crude product (gemcitabine hydrochloride content 99.32%, related impurity content 0.71%) to 10L water for injection, stir at room temperature until dissolved, add 50 g of activated carbon for decolorization for 10 minutes, filter, collect the filtrate, and set the temperature of the lyophilizer to At 5°C~10°C, place the filtrate in a lyophilizer and concentrate to 1.4L to obtain the gemcitabine hydrochloride concentrate; then add 4.2L of acetone to the gemcitabine hydrochloride concentrate, stir overnight at room temperature, and filter through a 0.22 μm microporous membrane. Washed with 1L of acetone, the filter cake was placed in a lyophilizer and dried to obtain 847.7 g of pure gemcitabine hydrochloride, with a yield of 85.3%. Sampled for HPLC, its purity was 99.98% (related impurity content 0.013%).

Embodiment 3

[0019] Add 1 kg of gemcitabine hydrochloride crude product (gemcitabine hydrochloride content 99.10%, related impurity content 0.92%) to 9L water for injection, stir at room temperature until dissolved, add 40 g of activated carbon for decolorization for 15 minutes, filter, collect the filtrate, and set the temperature of the lyophilizer to At 5°C~10°C, place the filtrate in a lyophilizer and concentrate to 1.1L to obtain gemcitabine hydrochloride concentrate; then add 2.2L acetone to the gemcitabine hydrochloride concentrate, stir overnight at room temperature, and filter through a 0.22 μm microporous membrane. Wash with 800mL of acetone, place the filter cake in a lyophilizer and dry to obtain 841.4g of pure gemcitabine hydrochloride, with a yield of 84.9%. Sampling for HPLC shows a purity of 99.98% (related impurity content 0.016%).

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Abstract

The invention provides a method for purifying gemcitabine hydrochloride, belonging to the technical field of compound purification. The method mainly comprises the steps of fetching a crude product of gemcitabine hydrochloride, and adding injection water for dissolution; adding active carbon for decoloration and filtering; concentrating the filtrate into a freeze dryer to obtain the gemcitabine hydrochloride concentrate; adding acetone into the gemcitabine hydrochloride concentrate; stirring overnight at room temperature; filtering and washing; drying the filter cake in the freeze dryer to obtain a pure product of gemcitabine hydrochloride. The method has the advantages that the implementation method is simple, the cost is low, the obtained gemcitabine hydrochloride has high purity and is suitable for industrial production, etc.

Description

[0001] technical field [0002] The invention belongs to the technical field of compound purification, in particular to a method for purifying crude gemcitabine hydrochloride. technical background [0003] Gemcitabine hydrochloride is an anti-metabolite tumor drug, its chemical name is (+)2'-deoxy-2',2'-difluorocytidine hydrochloride, its English name is Gemcitabine Hydrochloride, and its chemical structure is as follows: [0004] [0005] Compared with other anti-metabolite tumor drugs, gemcitabine hydrochloride has the advantages of stronger anti-tumor activity, wider anti-tumor spectrum, more significant therapeutic effect and lower toxicity, so it is widely used in non-small cell lung cancer, pancreatic cancer, breast cancer and other solid tumors. Because of its wide range of uses, the quality of gemcitabine hydrochloride is particularly important, and the process used to synthesize gemcitabine hydrochloride is likely to cause the appearance of α-isomers, cytosine a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H19/073C07H1/06
Inventor 阮诗文严海艳严恭超徐丽萍阮晓娜
Owner SHANGHAI DINGYA PHARM CHEM CO LTD
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