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Technique for preparing disodium valproate

A kind of sodium divalproex, the technology of preparation technology

Inactive Publication Date: 2010-05-12
QINGDAO UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

On the one hand, this can reduce the environmental pollution caused by toxic solvents, while reducing production costs; and in USP 6077542, divalproex sodium is prepared under solvent-free conditions, by dissolving sodium valproate in valproic acid and reacting , the disadvantage of this method is: the local concentration of valproic acid and sodium valproate is not uniform, so valproic acid and sodium valproate may be compounded in several proportions in the resulting product, the purity of the product is reduced, and the quality is not easy to control

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] At 55°C, add 14.4g of 0.1 mole of valproic acid and 16.6g of 0.1 mole of sodium valproate into 250ml of n-butanol for reaction, stir, and start vacuum distillation at the same time, keep the pressure at 300Pa, reduce the pressure Distill until no more solvent evaporated, and collect the white solid to obtain 29.1 g of divalproex sodium.

Embodiment 2

[0021] At 80°C, add 13.8g of 0.095 mole of valproic acid and 15.8g of 0.095 mole of sodium valproate into 250ml of isopropanol for reaction, stir, and start vacuum distillation at the same time, keep the pressure at 1500Pa, vacuum distillation Until no more solvent evaporated, the white solid was collected to obtain 27.8 g of divalproex sodium.

Embodiment 3

[0023] At 90°C, add 36.05g of 0.25 mole of valproic acid and 41.55g of 0.25 mole of sodium valproate into 500ml of glycerol for reaction, stir, and start vacuum distillation at the same time, keep the pressure at 1000Pa, vacuum distillation Until no more solvent evaporated, the white solid was collected to obtain 73.5 g of divalproex sodium.

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PUM

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Abstract

This invention discloses a process for preparing sodium divalproate. The process comprises: dissolving valproic acid and sodium valproate at a mol ratio of 1:1 in an appropriate solvent, and vacuum-distilling the solvent at 55-90 deg.C to obtain sodium divalproate. The process has such advantages as easy control, no byproducts, high product yield, high product quality, and low cost. The process can be used for mass production of sodium divalproate.

Description

1. Technical field [0001] The invention relates to the technical field of drug synthesis, in particular to the preparation process of divalproex sodium. 2. Background technology [0002] Divalproex sodium has 3 indications: epilepsy, migraine and bipolar affective disorder. It is widely used clinically and ranked 81st in the United States in 2001 by sales of prescription drugs. The chemical name of divalproex sodium is bis(2-propylvalerate) sodium hydrogen, and the molecular formula of divalproex sodium is: C 16 h 31 N a o 4 ;Molecular weight: 310.37. [0003] Valproic acid and sodium valproate are classical antiepileptic drugs widely used clinically. The molecular formula for valproic acid is C 8 h 16 o 2 , with a molecular weight of 144.21. Valproic acid is a liquid at room temperature, so it should not be prepared into convenient oral solid preparations such as tablets. Sodium valproate is the sodium salt of valproic acid, its molecular formula is C 8 h 15 o ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C51/41C07C53/128
Inventor 刘均洪邱龙辉张媛媛吕辉王繁业吴汝林孙岩
Owner QINGDAO UNIV OF SCI & TECH