Sugammadex sodium refining method capable of reducing purification loss rate

A technology of sugammadex sodium and a purification method, which is applied in chemical instruments and methods, inorganic chemistry, alkali metal compounds, etc., can solve the problems of difficult dissociation of resin adsorption, large loss rate, and low product yield, etc. Yield, convenient post-processing, the effect of reducing the loss rate

Active Publication Date: 2019-12-31
深圳市祥根生物有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, in the process of activated carbon adsorption in the above method, part of sugammadex sodium is adsorbed into the micropores of activated carbon together with impurities, resulting in a large loss rate and low product yield.
In addition, activated carbon should not be used in injections, and the purification process of activated carbon is difficult to meet the requirements of pharmaceutical production
[0008] CN109553702A discloses a method for purifying sugammadex sodium. The method uses an anionic functional group resin of a single-bonded tertiary

Method used

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  • Sugammadex sodium refining method capable of reducing purification loss rate

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0067] Preparation of Crude Sugammadex Sodium

[0068] Under nitrogen protection, 11.8 g of sodium hydride was added in batches to 550 ml of DMF; then a solution of 3-mercaptopropionic acid (15.8 g) dissolved in 100 ml of DMF solvent was added dropwise under ice-cooling. After the dropwise addition, stir at room temperature for 15 minutes, then raise the temperature to 70°C, slowly add 150ml of iodo-γ-cyclodextrin DMF solution dropwise under stirring condition, which contains 20.1g of iodo-γ-cyclodextrin; maintain the temperature and continue The reaction was stirred for 8h. After the reaction was completed, the reaction system was cooled to room temperature in an ice bath, 150 ml of deionized water was added, and the reaction was continued to stir for 2 h. After the reaction, the reaction solution was concentrated under reduced pressure to 260ml, then cooled in an ice bath, 1L of methanol was added to stir and crystallize, the solid was collected by suction filtration, and d...

preparation example 2

[0070] Preparation of PVA / sulfhydryl group co-modified magnetic polymer microspheres

[0071] (1) At 50°C, add 0.4mol / L of FeCl 2 solution and FeCl 3 The solution was added into a three-necked flask at a molar ratio of 1:2, stirred and mixed evenly to obtain a 240ml mixed solution; replaced by nitrogen, and under a nitrogen atmosphere, 28wt% ammonia water was added dropwise to the flask with a dropping funnel, and stirred while adding to The pH of the system is 11; then the temperature of the water bath is raised to the reaction temperature of 57°C, and the reaction is continuously stirred for 60 minutes. After the reaction is completed, the precipitate is collected by centrifugation, washed repeatedly with distilled water until neutral, dried, and ground to obtain powdered Fe 3 o 4 nuclear particles.

[0072] Take the above Fe 3 o 4 Disperse 8g of nuclear particles in 800mL of deionized water, adjust the pH value to 9.5 with 1M sodium hydroxide solution, and heat in a wa...

Embodiment 1

[0076] 1) Take 11.8 g of the sugammadex sodium raw material prepared above, heat and dissolve with 60 mL of deionized water, place it in a dialysis bag with a molecular weight cut-off of 1200 Da, and dialyze twice in distilled water at 45 °C for 60 min each time to remove small molecular impurities After dialysis, put it in a beaker in an ice bath to cool down, and at the same time, use 680mL of acetonitrile solvent to stir and crystallize. After the crystallization is completed, filter, collect the white solid, and dry 10.2g, which is the prefabricated crude product of sugammadex sodium. The HPLC purity is 95.62% .

[0077] 2) Take 10.0 g of the prefabricated crude product of sugammadex sodium after dialysis and place it in a three-neck flask with stirring, stir and dissolve it with 290 mL of deionized water at 50°C, and add acetic acid dropwise to adjust the pH of the solution to 6.2.

[0078] 3) Add 15 g of magnetic polymer microspheres co-modified with PVA / mercapto groups ...

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Abstract

The invention discloses a sugammadex sodium refining method capable of reducing the purification loss rate. The method utilizes magnetic polymer microspheres with PVA/sulfydryl group co-modified surfaces to purify acidified sugammadex sodium. The method provided by the invention achieves very high purification yield and purity, has mild purification conditions, avoids side reactions, reduces of the dosage of organic solvent, has environment-friendly process, is low in purification cost, and has substantially reduced purification loss rate.

Description

technical field [0001] The invention belongs to the technical field of medicine purification, and in particular relates to a method for refining and purifying sugammadex sodium. Background technique [0002] Sugammadex Sodium (Sugammadex Sodium, trade name Bridion) belongs to improved γ-cyclodextrin, is a chemical modification of cyclodextrin, and is also a steroid non-depolarizing muscle relaxant antagonist, which can interact with steroid Somatic muscle relaxants form inactive clathrates that antagonize neuromuscular blockade of varying depths. Sugammadex sodium is obtained by replacing all the 6-position hydroxyl groups in the 8 glucopyranose units of γ-cyclodextrin with carboxyethylthio groups. The synthesis method can be obtained by performing nucleophilic substitution reaction of 6-perdeoxy-6-perhalogenated-γ-cyclodextrin and 3-mercaptopropionic acid derivatives under alkaline conditions. WO0140316PP uses iodine as a halogenation reagent to react with γ-cyclodextrin ...

Claims

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Application Information

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IPC IPC(8): C08B37/16B01J20/26B01J20/28B01J20/30
CPCB01J20/265B01J20/28009B01J20/28021C08B37/0003C08B37/0012
Inventor 黄生宏李方林周佳
Owner 深圳市祥根生物有限公司
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