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Purification method of vinorelbine

A vinorelbine and purification method technology, applied in the direction of organic chemistry, can solve the problems of large consumption of organic solvent, cumbersome operation, high cost, etc., and achieve the effect of improving purity and yield, reducing production cost, and reducing usage

Active Publication Date: 2021-12-17
JIANGSU HANSOH PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, there are many patents reporting the purification method of vinorelbine, which are mainly divided into two categories. The first category is represented by "US4305875, US5220016, CN1552715, CN1552716A". This type of purification method is basically repeated through the alumina column And silica gel column purification, cumbersome operation, large consumption of organic solvent, serious environmental pollution, low yield; and the alumina and silica gel used cannot be reused, resulting in a large amount of solid waste, high cost, not suitable for industrial production
The second category is represented by "CN101284841A, CN101284842B", which combine silica gel column and reversed-phase column to separate and purify and then concentrate and dry to prepare vinorelbine tartrate. This type of method will also consume a large amount of organic solvents when purified by silica gel column, polluting the environment, The silica gel used also produces a large amount of solid waste because it cannot be reused; in addition, the purity of vinorelbine obtained by its reverse phase preparation is only 98.5%. When the purity is difficult to reach 95%, this method is also not suitable for industrialized large-scale production

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  • Purification method of vinorelbine
  • Purification method of vinorelbine
  • Purification method of vinorelbine

Examples

Experimental program
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Effect test

example 1

[0059] 1. Sample Preparation

[0060] Add L-(+) tartaric acid (760g) in the reaction bottle that vinorelbine (2000g, HPLC purity 85.679%) is housed, add purified water 8L again, stir to dissolve, feed liquid is passed through 0.45 micron filter membrane filtration, filtrate Dilute it with purified water, and prepare 20L of vinorelbine alkali feed solution for later use.

[0061] 2. Purification

[0062] 2.1 Equilibration of preparative chromatographic column:

[0063] First use mobile phase A as 5% anhydrous methanol and mobile phase B as 95% purified water for elution for 20 minutes, then use mobile phase A as 25% anhydrous methanol and mobile phase B as 75% sodium dihydrogen phosphate aqueous solution / anhydrous methanol for elution until complete column equilibration.

[0064] 2.3 Purification of samples

[0065] After the prepared chromatographic column is equilibrated, the sample solution is applied, and gradient elution is carried out according to the elution condit...

Embodiment 2

[0083] 1. Sample Preparation

[0084] Add L-(+) tartaric acid (800g) into a reaction flask equipped with vinorelbine (2100g, HPLC purity 85.435%), then add 10L of purified water, stir and dissolve, and filter the feed solution through a 0.45 micron membrane filter, and the filtrate Dilute with purified water, and prepare 25L of vinorelbine alkali feed solution, set aside.

[0085] 2. Purification

[0086] 2.1 Equilibration of preparative chromatographic column:

[0087] First use mobile phase A as 5% anhydrous methanol and mobile phase B as 95% purified water for elution for 20 minutes, then use mobile phase A as 25% anhydrous methanol and mobile phase B as 75% sodium dihydrogen phosphate aqueous solution / anhydrous methanol for elution until complete column equilibration.

[0088] 2.3 Purification of samples

[0089] After the prepared chromatographic column is equilibrated, the sample solution is applied, and gradient elution is carried out according to the elution cond...

example 3

[0108] 1. Sample Preparation

[0109] Add L-(+) tartaric acid (850g) into a reaction flask equipped with vinorelbine (2350g, HPLC purity 86.455%), then add 10L of purified water, stir and dissolve, and filter the feed solution through a 0.45 micron filter membrane, and the filtrate Dilute it with purified water, and prepare 26L of vinorelbine alkali feed solution for later use.

[0110] 2 purification

[0111] 2.1 Equilibration of preparative chromatographic column:

[0112] First, the mobile phase A was 5% acetonitrile, and the mobile phase B was 95% purified water for elution for 20 minutes, and then the mobile phase A was 20% acetonitrile, and the mobile phase B was 80% potassium dihydrogen phosphate aqueous solution. until column equilibration is complete.

[0113] 2.3 Purification of samples

[0114] After the prepared chromatographic column is equilibrated, the sample solution is applied, and the gradient elution is carried out according to the elution conditions in ...

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Abstract

A method for purifying vinorelbine, which uses a preparative chromatographic column for purification, including steps of sample preparation, purification, desalting and sample extraction, and the purity of vinorelbine obtained is above 99.4%. It is suitable for industrial production due to the problems of poor effect, low yield, cumbersome operation and large environmental pollution.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a purification method of vinorelbine. Background technique [0002] Vinorelbine tartrate (vinorelbine tartrate) was developed by the French company Pieer Fabre and was first listed in France in 1989. In 1993, my country approved its import as a cell cycle-specific broad-spectrum antineoplastic drug. Its trade name is Navelbing, and its chemical name is (3aR, 3a1R, 4R, 5S, 5aR, 10bR)- 4-Acetoxy-3a-ethyl-9-[(2R,6R,8S)-4-ethyl-8-(methylformyl)-1,3,6,7,8,9-hexahydro -2,6-methyleneazacyclodecyl[4,3-b]indol-8-yl]-5-hydroxy-8-methoxy-6-methyl-3a,3a1,4, Methyl 5,5a,6,11,12,-octahydro-1H-indolezine[8,1-cd]carbazole-5-carboxylate is the first-line drug for clinical treatment of non-small cell lung cancer and breast cancer patients . [0003] Vinorelbine tartrate is a semi-synthetic drug with complex chemical structure. Vinorelbine is its key intermediate. The specific structu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D519/04
CPCC07D519/04
Inventor 陈绍磊张小兵董月光徐进时祥
Owner JIANGSU HANSOH PHARMA CO LTD