Refining method of ibutilide fumarate

A technology of ibutilide fumarate and a purification method, applied in the field of medicine, can solve problems such as inability to achieve effective purification, and achieve the effects of reducing the number of times, simple process operations, and reducing production costs

Inactive Publication Date: 2011-04-27
YAOPHARMA CO LTD
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to the synthesis process disclosed in China Pharmaceutical Industry Journal. 2003, 34 (5). 209-211, the crude product of ibutilide fumarate wa

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Refining method of ibutilide fumarate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Add 10g crude ibutilide fumarate with a purity of 96.8% by HPLC into a three-necked reaction flask equipped with a stirring and reflux condenser, add 100ml of acetone, stir and heat to reflux, and add 0.5g activated carbon to decolorize for 20min after it is completely dissolved. Filtration; Slowly add 100ml of ether to the filtrate kept under reflux, stir vigorously, cool to 5℃ and let stand; separate the supernatant; add 100ml of acetone to the residue after heating to dissolve, cool to 5℃ to crystallize, filter Ibutilide fumarate can be obtained by drying under reduced pressure at 50°C. After drying, 8.7 g of the product was obtained, the yield was 87.0%, and the HPLC purity was 99.9%.

Embodiment 2

[0022] Add 10g of crude ibutilide fumarate with a HPLC purity of 96.8% into a three-necked reaction flask equipped with a stirring and reflux condenser, add 120ml of dichloromethane, stir and heat to reflux, and add 0.5g of activated carbon to decolorize for 20min after it is completely dissolved. Filter while it is hot; slowly add 120ml of ether to the filtrate kept under reflux, stir vigorously, cool to 5℃ and let stand; separate the supernatant; add 100ml of acetone to the residue after heating to dissolve, then cool to 5℃ to crystallize , Filtered, dried under reduced pressure at 50°C to obtain ibutilide fumarate. After drying, 8.1 g of the product was obtained, the yield was 81.0%, and the HPLC purity was 99.7%.

Embodiment 3

[0024] Add 10g crude ibutilide fumarate with a HPLC purity of 95.6% to a three-necked reaction flask equipped with a stirring and reflux condenser, add 120ml of acetone, stir and heat to reflux, and add 1g of activated carbon to decolorize for 30min after it is completely dissolved, and filter while hot ; Slowly add 200ml of ether to the filtrate kept under reflux, stir vigorously, cool to 5 ℃ and stand still; separate the supernatant; add 120ml of acetone to the residue after heating to dissolve, cool to 5 ℃ to crystallize, filter, Ibutilide fumarate is obtained by drying under reduced pressure at 50°C. After drying, 8.3 g of the product was obtained, the yield was 83.0%, and the HPLC purity was 99.7%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention relates to a refining method of ibutilide fumarate raw material medicine capable of resisting arrhythmia. The method comprises the following steps of: dissolving a crude ibutilide fumarate product into a solvent with stronger polarity or medium polarity, decoloring with activated carbon and filtering; then adding a solvent with smaller polarity to an obtained filter liquor, stirring, standing still and removing the supernate; adding a solvent with medium polarity to an obtained residue; and recrystallizing to obtain high-purity ibutilide fumarate. In the invention, impurities in the crude ibutilide fumarate product are effectively removed by adopting a mixed solvent eluting method, which improves the product purity, ensures that the product conforms to the medicinal requirement and guarantees the safety of clinical medication. The invention has the advantages of stable product quality and simple process operation and is suitable for mass industrial production.

Description

Technical field [0001] The invention belongs to the technical field of medicine, and relates to a method for refining an antiarrhythmic drug ibutilide fumarate raw material. Background technique [0002] Ibutilide Fumarate, chemical name (±)-N-[4-[4-(ethylheptylamino)-1-hydroxybutyl]phenyl]methanesulfonamide-2-butyl Alkenedioate is a class III antiarrhythmic drug with new ion channel activity developed by Pharmacia & Upjohn. It was approved by the FDA in December 1995 and listed in the United States in April 1996 under the trade name Convert. It has become the first choice for the treatment of newly-occurring atrial fibrillation and atrial flutter. It is also the only class III antiarrhythmic drug approved for the conversion of atrial fibrillation and atrial flutter in the United States. The curative effect of this product is better than antiarrhythmic drugs such as amiodarone, propoxone, procainamide, sotalol and amiodarone. The chemical formula of ibutilide fumarate is as fo...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07C311/08C07C303/44C07C303/36
Inventor 杨海川王信见
Owner YAOPHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap