Preparation method of andrographolide bulk pharmaceutical

Abstract

The invention discloses a novel preparation method of an andrographolide bulk pharmaceutical, belonging to the field of pharmaceutical chemistry. The method comprises the following steps of: reacting andrographolidume serving as a raw material with succinyl oxide under the action of a catalyst to obtain a 14-deoxy-11,12-didehydroandrographolidume-3,19-disuccinate (dehydroandrographolide succinate) intermediate at high yield and high quality; reacting the intermediate with a mixed salt; and crystalizing to directly obtain andrographolide which is consistent with an injection standard. The andrographolide bulk pharmaceutical has the advantages of mild reaction conditions, total reaction yield of over 70 percent and purity of over 98 percent, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of Yanhuning, which belongs to the field of medicinal chemistry. Background technique [0002] The chemical name of Yanhuning is 14-deoxy-11,12-didehydroandrographolide-3,19-disuccinic acid half ester sodium potassium salt, which has heat-clearing, detoxifying and anti-viral effects, and is mainly used for viral pneumonia and virus For acute upper respiratory tract infection, Yanhuning and its injection are included in the national drug standards. At present, the preparation method of Yanhuning has the following public literature reports: [0003] Invention patent CN1557812 "Andrographolide succinate half ester sodium potassium salt and its preparation" The method is to take the prescribed amount of Yanhuning, make a suspension with water for injection, and then use a certain amount of 2-4% sodium bicarbonate The solution is dissolved and clarified, and the pH value is adjusted within the range of 6.5-7.5...

AI Technical Summary

Problems solved by technology

The product yield is high, but without crystallization treatment, direct freeze-drying, energy consumption is large, and the by-products produced during the reaction process are not separated, which affects product quality

[0006] Invention patent CN101016283 "Preparation of Yanhuning by spray drying method" improves the solidification process of Yanhuning reaction solution, adds Yanhuning reaction solution into a spray dryer for spray drying to obtain Yanhuning finished product, this production method does not require Using organic solvents such as acetone and ethanol, the product yield is high, but the by-products generated during the reaction are also not separated, which affects product quality

This method is reflux reaction in a boiling water bath under the condition of vacuum degree of 520~620 mmHg. It is difficult to control in the actual operation process, and it is easy to resinize. It is not easy to crystallize and disperse after adding water to solidify in the post-treatment, and the product color is yellowish.

"Synthetic process improvement of dehydroandrographolide disuccinic acid half ester" (2006 "Anhui Medicine") improved the above process, added a large amount of antioxidants to the reaction system, and canceled the vacuum reaction condition, but the product yield was only 41.7%, no industrial value