Preparation method of potassium sodium dehydroandroandrographolide succinate

A technology of Yanhuning and succinic acid, which is applied in the field of preparation of Yanhuning, can solve the problems of substances exceeding the standard, producing impurities, affecting the safety of medication, etc.

Active Publication Date: 2018-09-07
HEILONGJIANG ZBD PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the presence of two ester bonds and one lactone bond in the molecular structure of Yanhuning, its chemical stability is poor, and impurities are likely to be produced in the half-ester synthesis process and the salt-forming step, resulting in excessive levels of related substances and seriously affecting the safety of the drug.

Method used

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  • Preparation method of potassium sodium dehydroandroandrographolide succinate
  • Preparation method of potassium sodium dehydroandroandrographolide succinate
  • Preparation method of potassium sodium dehydroandroandrographolide succinate

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preparation example Construction

[0013] This embodiment provides a method for preparing Yanhuning, which includes the following steps:

[0014] Step S1, salt forming step: dissolving dehydroandrographolide succinic acid half ester, reacting with sodium carbonate salt and potassium carbonate salt to form a salt, and obtaining Yanhuning crystallization liquid after filtration.

[0015] Wherein, the molecular formula of dehydroandrographolide succinate half ester is as follows:

[0016]

[0017] Further, in the salt-forming reaction, the dehydroandrographolide succinate half ester is dissolved in a 35-65 Vol% organic solvent-water mixed solution system. Preferably, in the mixed solution system, the volume fraction of the organic solvent is 35-58 Vol%, or 38-52 Vol%, or 40-50 Vol%, or 42-48 Vol%. Preferably, the organic solvent in the mixed solution system is selected from the group consisting of ethanol, methanol, acetone, isopropanol or ethyl acetate.

[0018] Preferably, the mass volume ratio of the dehyd...

Embodiment 1

[0044] This embodiment provides a preparation method of Yanhuning, which includes:

[0045] a. Esterification reaction: using pyridine as the reaction solvent, mix andrographolide and succinic anhydride in a molar ratio of 1:6, carry out esterification reaction at 80°C under nitrogen protection, and the reaction time is 10h; after the reaction Crystallize with water as a solvent, let it stand for 8 hours, and centrifuge or filter to obtain the crude product of dehydrated andrographolide succinic acid half ester.

[0046] b. Refining step: the crude product of dehydroandrographolide succinate half ester is heated under nitrogen protection (heating to a temperature of 55°C) and dissolved in 55Vol% acetone-water solution, and the crude product of dehydroandrographolide succinate half ester is mixed with The mass volume ratio of acetone-water solution is 1:5. Then the temperature was slowly lowered to room temperature, stirred slowly for 2 hours, and then cooled to -4°C for 10 ho...

Embodiment 2

[0052] This embodiment provides a preparation method of Yanhuning, which includes:

[0053] a. Esterification reaction: using pyridine as the reaction solvent, mix andrographolide and succinic anhydride at a molar ratio of 1:3.5, and carry out esterification reaction at 100°C under the protection of nitrogen, and the reaction time is 8 hours; after the reaction Crystallize with water as a solvent, let it stand for 4 hours, centrifuge or filter, and obtain the crude product of dehydrated andrographolide succinate half ester.

[0054] b. Refining step: the crude product of dehydroandrographolide succinate half ester is heated under nitrogen protection (heating to a temperature of 40°C) and dissolved in 75Vol% methanol-water solution, and the crude product of dehydroandrographolide succinate half ester is mixed with The mass volume ratio of methanol-water solution is 1:2.5. Then the temperature was lowered to -10°C for 2 h of crystallization. After filtering, wash the obtained ...

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Abstract

The invention provides a preparation method of potassium sodium dehydroandroandrographolide succinate, and belongs to the field of pharmacy. The preparation method comprises the steps that dehydroandrograpolide succinate is dissolved and then subjected to a salt forming reaction with sodium carbonate salt and potassium carbonate salt, and potassium sodium dehydroandroandrographolide succinate liquid to be crystallized is obtained after filtration; the potassium sodium dehydroandroandrographolide succinate liquid to be crystallized is added in an organic solvent, evenly filtered and then crystallized, and filter cakes obtained after filtration are beaten with an organic solvent 2-3 times. According to the preparation method, dehydroandrograpolide succinate is subjected to the salt forming reaction and crystallized in the organic solvent on the premise of controlling the temperature, and related impurities are reduced. According to potassium sodium dehydroandroandrographolide succinate prepared by means of the method, the total yield is greater than 75%, the purity is greater than 98.5%, the content of the related impurities is smaller than 0.8%, the ratio of sodium ions to potassiumions is 1:(0.9-1.1), the moisture content is not greater than 3.5%, and the quality control standards of potassium sodium dehydroandroandrographolide succinate are met.

Description

technical field [0001] The invention relates to the field of medicine preparation, in particular to a preparation method of Yanhuning. Background technique [0002] Yanhuning, its chemical name is 14-dehydroxy-11,12-didehydroandrographolide-3,19-disuccinic acid half ester potassium sodium salt monohydrate, and its molecular formula is C 28 h 34 o 10 KNa·H 2 O, its molecular weight is 610.68, and its structural formula is as follows: [0003] [0004] Yanhuning is obtained from the andrographolide extracted from the leaves of the traditional Chinese medicine Andrographis paniculata through esterification, dehydration, and salt formation. It has the functions of clearing away heat, antibacterial, anti-inflammatory, and antiviral. It is mainly used for viral pneumonia, upper respiratory tract infection, acute and chronic bronchial Inflammation, gastrointestinal infection, etc. Due to the existence of two ester bonds and one lactone bond in the molecular structure of Yan...

Claims

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Application Information

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IPC IPC(8): C07D307/58
CPCC07D307/58
Inventor 方同华李天翥王春生李卯陈景超
Owner HEILONGJIANG ZBD PHARMA
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