Preparation method for sugammadex sodium

A technology of sugammadex sodium and cyclodextrin, which is applied in the field of drug preparation, can solve the problems of difficult separation of impurities, gelation, and large ethanol consumption, and achieve simple purification process, mild operating environment, and increased yield Effect

Active Publication Date: 2015-08-19
SHANDONG BINZHOU ZHIYUAN BIO TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] 1. Sodium hydride is a highly dangerous substance. A large amount of hydrogen generated after feeding is also a flammable and explosive gas. At the same time, sodium hydride is dispersed and stored in mineral oil, which will introduce a large amount of unknown impurities to the reaction and affect the purity of the final product;
[0012] 2. The reaction requires anhydrous, but anhydrous conditions are extremely complicated for cyclodextrin molecules with cavities. A small amount of water mixed into the reaction will lead to 7 or 6 substitutions in the product. This impurity with less than 8 substitutions Extremely difficult to separate, affecting product purity;
[0013] 3. Sodium hydride in N,N-dimethylformamide is very prone to gelation,...

Method used

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  • Preparation method for sugammadex sodium
  • Preparation method for sugammadex sodium
  • Preparation method for sugammadex sodium

Examples

Experimental program
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Effect test

Embodiment 1

[0053] A preparation method of sugammadex sodium, comprising steps as follows:

[0054] (1) Add 20g (13.9mmol) of 6-perdeoxy-6-perchloro-γ-cyclodextrin and 42g (556mmol) of thiourea into 600ml of N,N-dimethylformamide, stir at 90°C React for 12 hours; first concentrate the reaction solution under reduced pressure until the volume of the reaction solution is 1 / 4 of the volume of N,N-dimethylformamide, and then add ethanol 8 times the volume of the concentrated solution for precipitation. The obtained solid precipitate was added into 750 ml of aqueous sodium hydroxide solution with a concentration of 0.25 mol / L and stirred at 90° C. for 2 hours to obtain a mixed reaction solution. The volume of the liquid was concentrated under reduced pressure to 1 / 4 of the volume of the mixed reaction solution. Adjust the pH to 2, add ethanol 8 times the volume of the reaction solution to the pH-adjusted reaction solution for precipitation, wash the precipitate with ice water, and then recryst...

Embodiment 2

[0060] A preparation method of sugammadex sodium, comprising steps as follows:

[0061] (1) Add 20g (13.9mmol) of 6-perdeoxy-6-perchloro-γ-cyclodextrin and 42g (556mmol) of thiourea into 600ml of N,N-dimethylformamide, stir at 90°C React for 12 hours; first concentrate the reaction solution under reduced pressure until the volume of the reaction solution is 1 / 4 of the volume of N,N-dimethylformamide, and then add ethanol 6 times the volume of the concentrated solution for precipitation. The obtained solid precipitate was added into 750 ml of aqueous sodium hydroxide solution with a concentration of 0.25 mol / L and stirred at 90° C. for 2 hours to obtain a mixed reaction solution. The volume of the liquid was concentrated under reduced pressure to 1 / 4 of the volume of the mixed reaction solution. Adjust the pH to 2, add ethanol 6 times the volume of the reaction solution to the adjusted pH value of the reaction solution for precipitation, wash the precipitate with ice water, and...

Embodiment 3

[0068] With the sugammadex sodium preparation method described in embodiment 1, the difference is:

[0069] In step (1), add 24g of 6-perdeoxy-6-periodo-γ-cyclodextrin and 42g of thiourea into 600ml of N,N-dimethylformamide, heat to 85°C, and react under stirring for 12 hours , first concentrate the reaction solution under reduced pressure until the volume of the reaction solution is 1 / 4 of the volume of N,N-dimethylformamide, and then add ethanol 9 times the volume of the concentrated solution for precipitation. The obtained solid precipitate was added into 750 ml of aqueous sodium hydroxide solution with a concentration of 0.2 mol / L and stirred at 85° C. for 2 hours to obtain a mixed reaction solution. The volume of the liquid was concentrated under reduced pressure to 1 / 4 of the volume of the mixed reaction solution. Adjust the pH to 2, add ethanol 9 times the volume of the reaction solution to the pH-adjusted reaction solution for precipitation, wash the precipitate with i...

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Abstract

The invention relates to a preparation method for a muscle relaxing antagonistic agent sugammadex sodium. The preparation method comprises the following steps: preparing sulfydryl gamma-cyclodextrin by taking halogenated gamma-cyclodextrin and thiourea as reactants; then, initiating sulfydryl-alkene click reaction by illuminating or using an initiator on sulfydryl gamma-cyclodextrin with acrylic acid or acrylic esters or sodium acrylate so as to prepare high-purity sugammadex sodium in a water phase. According to the preparation method for the sugammadex sodium, the the operation environment is gentle, the yield is increased, and the purifying process for the final product sugammadex sodium is simpler.

Description

technical field [0001] The invention relates to a preparation method of medicine, in particular to a preparation method of sugammadex sodium, a muscle relaxant antagonist. Background technique [0002] Sugammadex sodium: chemical name: 6-full deoxy-6-full (2-carboxyethyl) thio-γ-cyclodextrin sodium salt, English: Suγdex, trade name: Bridion, the earliest sugammadex sodium Discovered by Organon Biosciences, which was acquired by Schering-Plough in 2007. Schering-Plough merged with Merck in 2009. Sugammadex sodium is currently owned and sold by Merck. [0003] In 2008, the FDA was concerned that it might cause allergic reactions, so it rejected Schering-Plough’s listing application for sugammadex sodium; at the end of 2009, sugammadex sodium was approved for marketing in Europe; soon Merck began to set up 11 clinical medical centers in China, and launched sugammadex sodium. Phase III clinical study of sodium gluconate in China. [0004] Sugammadex sodium is used to reverse...

Claims

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Application Information

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IPC IPC(8): C08B37/16
Inventor 陈晋波申健李媛媛
Owner SHANDONG BINZHOU ZHIYUAN BIO TECH CO LTD
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