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Clexane and preparation method thereof

A technology of enoxaparin and heparin sodium, applied in the field of biochemical products and its preparation, can solve the problems of high processing cost, unstable product quality, and low yield

Active Publication Date: 2010-01-20
JIANGSU ALAND NOURISHMENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, there are also defects such as unstable product quality, high processing costs, and relatively low yields.

Method used

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  • Clexane and preparation method thereof

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Embodiment Construction

[0008] The enoxaparin and its preparation method of the present invention are: dissolving heparin sodium in 7-11 times of water at normal temperature, adjusting the pH to 7.0-9.0; dissolving 2-3 times of heparin sodium in 3-7 times of water, And stir evenly, add the heparin sodium aqueous solution to the benzethonium chloride aqueous solution to fully react, then vacuum filter, the vacuum degree is ≥0.08MPa, the solid is then stirred and washed with water, and then suction filtered, repeat twice, the solid is stored at 45-60 ° C, Dry it for 20-30 hours to obtain heparin quaternary ammonium salt in the form of sodium salt. Dissolve heparin quaternary ammonium salt in 3 to 7 times of dichloromethane, add 1 to 4 times of benzyl chloride, place the reaction solution in an aqueous solution at 20 to 45°C, take it out after reacting for 20 to 30 hours, add 1 times of total 10% methanol solution of sodium acetate in the reaction volume, suction filtration, the solid is then stirred an...

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Abstract

The present invention is enoxaparin and its preparation process, and features that the preparation process includes the following steps: dissolving sodium heparin in water, dissolving benzethonium chloride in water, mixing these two kinds of solution to react, vacuum suction filtering, washing the solid with water and stoving to obtain quaternary ammonium salt of heparin; dissolving the salt in dichloromethane, adding benzyl chloride to react, adding methanol solution of sodium acetate to produce precipitate, suction filtering, washing the solid with methanol and stoving to obtain heparin benzyl ester; dissolving heparin benzyl ester in 0.1N water solution of sodium hydroxide, adding sodium chloride, membrane filtering after dissolving, adding methanol to separate out precipitate, suction filtering, washing and stoving solid to obtain coarse enoxaparin sodium product; and purifying to obtain refined enoxaparin sodium product. The present invention has low production cost and high product quality.

Description

Technical field: [0001] The invention discloses a biochemical product called enoxaparin and a preparation method thereof. The preparation method belongs to a preparation method of biochemical medicines. technical background: [0002] Enoxaparin is an anticoagulant and antithrombotic drug, a derivative of low molecular weight heparin sodium. Enoxaparin is obtained from porcine intestinal mucosal heparin through quaternization, esterification, and β-elimination in alkaline solution. There are many preparation methods of enoxaparin, but the following two preparation methods are commonly used at present: [0003] Method 1: adding an aqueous solution of benzethonium chloride to the acidic aqueous solution of heparin, washing the obtained precipitate with water, and drying in vacuum to obtain a quaternary ammonium salt of heparin. Esterify heparin quaternary ammonium salt and p-chlorobenzyl in N,N-dimethylformamide (DMF) at room temperature for 48 hours to obtain heparin 4-chlo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08B37/10A61K31/727A61P7/02
Inventor 夏旭东史解矛秦苏东
Owner JIANGSU ALAND NOURISHMENT
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