Preparation method of andrographolide bulk pharmaceutical

A technology of raw material medicine, Yanhuning, applied in the field of preparation of Yanhuning, can solve the problems of difficult control, easy resinization, difficult crystallization and evacuation, etc.

Active Publication Date: 2012-07-18
KAIFENG PHARMA GRP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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 s

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] 1) Preparation of 14-deoxy-11,12-didehydroandrographolide-3,19-disuccinate half ester (dehydroandrographolide succinate half ester)

[0020] Put 500 g (1.42 mol) of andrographolide, 510 g (5.1 mol) of succinic anhydride, 5 g of DABCO, and 1200 mL of pyridine in a reaction flask, heat to 80°C under nitrogen protection under stirring, and keep at this temperature for 7 hours , recover pyridine under reduced pressure, lower the temperature to 50°C, add 2500 mL of 30% by mass acetic acid aqueous solution to crystallize, filter, and recrystallize the resulting solid with 75% by mass ethanol, filter and dry to obtain 734 grams of dehydroandrographolide succinate half ester , milky white solid, yield 94%.

[0021] 2) Preparation of 4-dehydro-11,12-didehydroandrographolide-3,19-disuccinic acid half ester sodium potassium salt (Yanhuning)

[0022] 500 g (0.91 mol) of the dehydrated andrographolide succinate half ester prepared above, 1500 mL of ethanol with a mass percentage of...

Embodiment 2

[0024] 1) Preparation of 14-deoxy-11,12-didehydroandrographolide-3,19-disuccinate half ester (dehydroandrographolide succinate half ester)

[0025] Put 500 g (1.42 mol) of andrographolide, 568 g (5.68 mol) of succinic anhydride, 8 g of DMAP, and 1000 mL of pyridine in a reaction flask, stir and heat to 100°C under nitrogen protection, and keep at this temperature for 4 hours. Recover pyridine under reduced pressure, lower the temperature to 30°C, add 3000 mL of 20% by mass acetic acid aqueous solution to crystallize, filter, and recrystallize the obtained solid with 75% by mass ethanol, filter and dry to obtain 718 grams of dehydroandrographolide succinate half ester , milky white solid, yield 92%.

[0026] 2) Preparation of 4-dehydro-11,12-didehydroandrographolide-3,19-disuccinic acid half ester sodium potassium salt (Yanhuning)

[0027] 500 grams (0.91 mol) of the dehydrated andrographolide succinate half ester prepared above, 1500 mL of acetone with a mass percentage of 60...

Embodiment 3

[0029] 1) Preparation of 14-deoxy-11,12-didehydroandrographolide-3,19-disuccinate half ester (dehydroandrographolide succinate half ester)

[0030]Put 500 g (1.42 mol) of andrographolide, 568 g (5.68 mol) of succinic anhydride, 3 g of DMF, and 1500 mL of pyridine in a reaction flask, heat to 70°C under nitrogen protection under stirring, and keep at this temperature for 6 hours , reclaim pyridine under reduced pressure, directly add 2500 mL of acetic acid aqueous solution of 30% by mass to crystallize, filter, and recrystallize the gained solid with 75% by mass of ethanol, filter and dry to obtain 703 grams of dehydroandrographolide succinate half ester, milky white solid , yield 90%.

[0031] 2) Preparation of 14-deoxy-11,12-didehydroandrographolide-3,19-disuccinic acid half ester sodium potassium salt (Yanhuning)

[0032] 500 g (0.91 mol) of the dehydrated andrographolide succinate half ester prepared above, 2000 mL of 70% propanol by mass percentage, heated to a constant t...

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PUM

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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...

Claims

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Application Information

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IPC IPC(8): C07D307/58
Inventor 徐海伟朱松林季明志冯俊平苑鹏飞黄占海裴珊珊冯汉书马芳郑丰渠
Owner KAIFENG PHARMA GRP
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