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A kind of refining method of topiramate

A refining method and technology of topiramate, applied in chemical instruments and methods, preparation of sugar derivatives, organic chemistry, etc., can solve the problems that the purification technology cannot meet the requirements for the production of pharmaceutical grade topiramate, and fail to achieve simple impurities, so as to avoid multiple One-step purification operation, shortening production cycle, improving economy and safety

Active Publication Date: 2021-07-02
LUNAN BETTER PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] In summary, each preparation method utilizes different ammonia sources to successfully synthesize topiramate, and the product purity can reach more than 99.0%, which has achieved fruitful research progress. However, in the ammonolysis reaction process, each preparation method produces a retention time of For the degraded impurities at 7.6min and 31min, although the purification process of each method has done multi-step purification, they all failed to meet the requirement of less than 0.1% of simple impurities. Therefore, the purification techniques of the existing preparation methods cannot meet the requirements Requirements for the production of pharmaceutical grade topiramate

Method used

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  • A kind of refining method of topiramate
  • A kind of refining method of topiramate
  • A kind of refining method of topiramate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Get topiramate crude product, carry out refining according to the following steps:

[0036] Add 1kg of 2,3:4,5-bis-O-(1-methylethylene)-β-D-fructopyranose sulfamate oily liquid to 0.5L methanol and 0.5L ethanol, heat to reflux until dissolved , then lower the temperature to 55°C, adjust the pH to 9.0 with 20% ammonia water by mass fraction, and obtain system I;

[0037] Stir and keep warm at 50°C, add 10L of petroleum ether dropwise to System I, after 1.5h, the dropwise addition is completed, then cool down to room temperature naturally, and stand for crystallization for 8 hours to obtain System II;

[0038] The system II was filtered, and the filter cake was put into 1 L of petroleum ether for rapid stirring and grinding, filtered, and vacuum-dried to obtain pure topiramate crystals with a yield of 93.8%. The obtained pure topiramate crystals were detected by HPLC, and the results showed that the purity calculated by the external standard method was 99.86%, and the im...

Embodiment 2

[0040] Get topiramate crude product, carry out refining according to the following steps:

[0041] Add 1 kg of 2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopyranose sulfamate oily liquid to 4L propanol, heat to reflux until dissolved, then cool down to At 55°C, adjust the pH to 9.2 with 20% ammonia water to obtain System I;

[0042] Stir and keep warm at 52°C, add 5 L of ethylene glycol dimethyl ether dropwise to System I, after 1.2 hours, the dropwise addition is completed, cool down to room temperature naturally, and stand for crystallization for 9 hours to obtain System II;

[0043] The system II was filtered, and the filter cake was put into 3 L of ethylene glycol dimethyl ether for rapid stirring and grinding, filtered, and vacuum-dried to obtain pure topiramate crystals with a yield of 95.1%. The obtained pure topiramate crystals were detected by HPLC, and the results showed that the calculated purity by the external standard method was 99.85%, and the impurities with r...

Embodiment 3

[0045] Get topiramate crude product, carry out refining according to the following steps:

[0046] Add 1kg of 2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopyranose sulfamate oily liquid to 5L of ethanol, heat to reflux until dissolved, then cool down to 57 °C, adjust the pH to 9.5 with 25% ammonia water to obtain system I;

[0047] Stir and keep warm at 55°C, add 3 L of petroleum ether dropwise to System I, after 1.2 hours, the dropwise addition is completed, then cool down to room temperature naturally, and stand for crystallization for 10 hours to obtain System II;

[0048] The system II was filtered, and the filter cake was put into 5 L of petroleum ether, ethylene glycol dimethyl ether, and methyl tert-butyl ether, stirred and ground rapidly, filtered, and vacuum-dried to obtain pure topiramate crystals with a yield of 92.2%. The obtained pure topiramate crystals were detected by HPLC, and the results showed that the purity of topiramate calculated by the external standar...

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Abstract

The invention relates to a refining method for preparing pharmaceutical-grade topiramate. Through one-step refining, the single impurity of the product is less than 0.1%, and the total impurities are less than 0.5%, which meets the industrial production requirements of pharmaceutical-grade topiramate. The method avoids tedious multi-step purification operations, shortens the production cycle, requires simple production equipment, and improves economy and safety.

Description

technical field [0001] The invention belongs to the field of pharmacy and relates to a refining method for preparing pharmaceutical grade topiramate. Background technique [0002] Topiramate, trade name Topamax, chemical name 2,3:4,5-bis-O-(1-methylethylene)-β-D-fructopyranose sulfamate, The structural formula is as follows: [0003] [0004] It was developed by Johnson & Johnson in the United States and launched in the UK in 1995. It was approved by the FDA in 1996 for the treatment of primary partial epilepsy in adults and in 2000 for the treatment of children with epilepsy. In 2004, the FDA approved the drug for the prevention of migraine in adults. In July 2012, the FDA approved the launch of Qsymia, a compound weight-loss drug containing topiramate and phentermine from Vivus Pharmaceuticals of the United States. It is the second new weight-loss drug approved by the United States in 13 years. [0005] As a new type of antiepileptic drug, topiramate has ideal pharma...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H9/04C07H1/00C07H1/06
CPCC07H1/00C07H1/06C07H9/04
Inventor 张贵民苗宇李莹
Owner LUNAN BETTER PHARMA
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