Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof

A technology of Yanhuning and succinic acid, applied in the field of preparation of Yanhuning, can solve the problems of low product purity, unstable storage, complicated reaction and the like, and achieve the effects of high product purity, good solubility and simplified reaction steps.

Active Publication Date: 2007-03-14
珠海晨安医药有限公司
View PDF1 Cites 35 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The reaction of the above-mentioned preparation method is complex and difficult to control, the yield is low, the product purity is not high, the storage is unstable, and side effects such as allergies may occur during use

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] 1). Preparation of 14-dehydro-11,12 didehydroandrographolide-3,19-disuccinic acid (dehydroandrographolide succinate half ester):

[0041] Put 300 grams (0.86mol) of andrographolide, 400 (4.39mol) grams of succinic anhydride, and 600ml of (1:5.1) pyridine in a reaction flask, mix well, heat to 50°C under nitrogen protection and keep at this temperature for 15 Then heat up to the boiling point of pyridine and reflux for 5 hours, reclaim pyridine under reduced pressure, drop to room temperature, add 1L water to stir and crystallize, filter, and wash the solid 3 times with 1L water, dry to obtain a white solid (dehydroandrographolide succinic acid semi ester) 311 grams, yield 68.1%.

[0042] 2). Preparation of Yanhuning: 311 grams (0.58 mol) of dehydrated andrographolide succinate half ester, 1 L of water and 77 grams of potassium carbonate were stirred and reacted for 5 hours, and 20% sodium carbonate aqueous solution was added dropwise at room temperature to pH The value...

Embodiment 2

[0044] Put 300 grams (0.86mol) of andrographolide, 340 (3.39mol) grams of succinic anhydride, and 900ml (1:3.95) pyridine in a reaction flask, mix well, heat to 90°C under nitrogen protection and keep at this temperature for 8 Then heat up to the boiling point of pyridine and reflux for 1 hour, reclaim pyridine under reduced pressure, drop to room temperature, add 1L water to stir and crystallize, filter, and the solid is washed 4 times with 0.8L water, and dry to obtain a white solid (dehydroandrographolide succinic acid half ester) 301 g.

[0045] 301 g (0.56 mol) of dehydrated andrographolide succinate half ester, 1 L of water and 60 g of potassium bicarbonate were stirred and reacted for 8 hours, and 10% aqueous sodium hydroxide solution was added dropwise at room temperature until the pH value was 7-8; Filtrate, add 4L of absolute ethanol to the filtrate, stir, evaporate the solvent below 40°C, add 5L of acetone and stir for 2 hours, filter with suction, if necessary, con...

Embodiment 3

[0047] Put 300 grams (0.86mol) of andrographolide, 516 (5.16mol) grams of succinic anhydride, and 1176ml of (1:6) pyridine in a reaction flask, mix well, heat to 70°C under nitrogen protection and keep at this temperature for 5 Then heat up to the boiling point of pyridine and reflux for 3 hours, reclaim pyridine under reduced pressure, drop to room temperature, add 0.8L water to stir and crystallize, filter, the solid is washed 4 times with 0.5L water, and dry to obtain a white solid (dehydroandrographolide amber Acid half ester) 386 grams.

[0048] 386 grams (0.72 mol) of dehydrated andrographolide succinic acid half ester, 1 L of water and 44 grams of potassium hydroxide were stirred for 5 hours, and 10% aqueous sodium hydroxide solution was added dropwise at room temperature until the pH value was 7-8; Filtrate, add 4L of absolute ethanol to the filtrate, stir, evaporate the solvent below 35°C, add 5L of inner ketone and stir for 4 hours, filter with suction, wash once mor...

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 present invention relates to the preparation process and preparation of Yanuning. Yanuning is prepared through an esterification reaction and a salt-forming reaction. During the esterification reaction, andrographolide and succinic anhydride react in pyridine solution and the resultant is post-treated to obtain dehydroandrographolide semi-succinate. During the salt-forming reaction, dehydroandrographolide semi-succinate and KOH, KHCO3 or K2CO3 react in water to form monopotassium salt of dehydroandrographolide semi-succinate, and through post-treatment, Yanuning is prepared. The present invention has mild reaction condition and nitrogen protection to avoid oxidation and degradation, excessive pyridine added into the reaction for dewatering without need of vacuumizing, and heating reflux in the later reaction stage for complete reaction.

Description

field of invention [0001] The invention relates to a preparation method of Yanhuning, its preparation and its preparation method. Background technique [0002] The scientific name of Yanhuning is 14-dehydro-11,12-didehydroandrographolide-3,19-disuccinic acid half ester potassium sodium salt or its hydrate, Yanhuning and its injection were released in 2002 It is included in the drug standards. At present, the preparation method of Yanhuning is disclosed in the invention patent of Chinese patent application CN1557812, title: sodium potassium salt of half ester succinate of andrographolide and its preparation. According to the content of the patent, its preparation method is as follows: mainly: take the prescribed amount of Chuanhuning, add 20% water for injection to make a suspension; take the prescribed amount of NaHCO 3 , add water for injection to make 2-4% NaHCO 3 Solution 6500ml; control the temperature of the above suspension at 35±5°C, and 2 With constant stirring, ...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/58A61K31/365A61K9/19A61P11/00A61P11/04A61P1/04A61P1/16A61P13/02
Inventor 黄金秀
Owner 珠海晨安医药有限公司
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