Preparation method for sugammadex sodium

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...

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, which makes the edge of the reaction vessel unable to be stirred and dispersed, making the reaction uneven;

[0014] 4. After the reaction of the N,N-dimethylformamide organic solvent system, the ethanol precipitation process is required, which consumes a large amount of ethanol, and after the ethanol is mixed with N,N-dimethylformamide, the two organic solvents cannot be recovered to apply

[0015] When the above two preparation processes are synthesized on a small scale in the laboratory, the existing problems can be ignored, but after the further expansion of the preparation scale, the above defects will become more prominent, thereby affecting the quality of the final product and increasing the cost, and are not suitable for large-scale production.

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