A kind of preparation method of Yanhuning

A technology of Yanhuning and succinic acid, which is applied in the field of preparation of Yanhuning, can solve the problems of affecting drug safety, poor chemical stability, and excessive substances

Active Publication Date: 2022-06-24
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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  • A kind of preparation method of Yanhuning
  • A kind of preparation method of Yanhuning
  • A kind of preparation method of Yanhuning

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preparation example Construction

[0013] The present embodiment provides a preparation method of Yanhuning, which comprises the following steps:

[0014] Step S1, the salt-forming step: dissolving the dehydrated andrographolide succinic acid half-ester to undergo a salt-forming reaction with sodium carbonate and potassium carbonate, and filtering to obtain a crystallization solution of Yanshuning.

[0015] Wherein, the molecular formula of dehydrated andrographolide succinic acid half ester is as follows:

[0016]

[0017] Further, in the salt-forming reaction, the dehydrated andrographolide succinic acid 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] Preferab...

Embodiment 1

[0044] The present embodiment provides a preparation method of Yanhuning, comprising:

[0045] a. Esterification reaction: using pyridine as the reaction solvent, andrographolide and succinic anhydride were mixed in a molar ratio of 1:6, and the esterification reaction was carried out at 80°C under nitrogen protection, and the reaction time was 10h; Crystallization was carried out with water as a solvent, left standing for 8 hours, and after centrifugation or filtration, the crude product of dehydrated andrographolide succinic acid half ester was obtained.

[0046] b. Refining step: the obtained dehydrated andrographolide succinate half-ester crude product is heated under nitrogen protection (heating to a temperature of 55° C.) and dissolved in 55Vol% acetone-aqueous solution, the dehydrated andrographolide succinate half-ester crude product and The mass-volume ratio of acetone-water solution is 1:5. Then slowly cooled to room temperature, slowly stirred for 2 h, and then coo...

Embodiment 2

[0052] The present embodiment provides a preparation method of Yanhuning, comprising:

[0053] a. Esterification reaction: using pyridine as the reaction solvent, andrographolide and succinic anhydride were mixed in a molar ratio of 1:3.5, and the esterification reaction was carried out at 100 ° C under nitrogen protection, and the reaction time was 8h; after the reaction was completed Crystallize with water as solvent, stand for 4 hours, centrifuge or filter to obtain the crude product of dehydrated andrographolide succinic acid half ester.

[0054] b. Refining step: the obtained dehydrated andrographolide succinic acid half-ester crude product is heated under nitrogen protection (heated to a temperature of 40° C.) and dissolved in 75Vol% methanol-water solution, the dehydrated andrographolide succinic acid half-ester crude product is mixed with The mass-volume ratio of methanol-water solution is 1:2.5. Then it was cooled to -10 °C for 2 h. After filtration, the obtained fi...

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Abstract

The invention provides a preparation method of Yanhuning, which belongs to the field of pharmacy. The preparation method comprises: dissolving dehydrated andrographolide succinic acid half ester, reacting with sodium carbonate salt and potassium carbonate salt to form a salt, and obtaining Yanhuning crystallization liquid after filtration; adding Yanhuning crystallization liquid to organic After stirring evenly in a solvent, crystallize, filter and beat the obtained filter cake with an organic solvent for 2 to 3 times. In the preparation method, dehydroandrographolide succinate half ester is subjected to a salt-forming reaction, and crystallization is carried out in an organic solvent under the premise of temperature control, so as to reduce related impurities. The total yield of Yanhuning prepared by this method is greater than 75%, the purity is greater than 98.5%, the related impurities are less than 0.8%, the ratio of sodium and potassium ions is 1:0.9~1.1, and the water content is not more than 3.5%, which meets the requirements of Yanhuning. Ning quality control standards.

Description

technical field [0001] The invention relates to the field of pharmaceutical 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, the 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 prepared from andrographolide extracted from the leaves of Andrographis paniculata by esterification, dehydration and salt formation. It has the functions of clearing heat, antibacterial, anti-inflammatory and antiviral. It is mainly used for viral pneumonia, upper respiratory tract infection, acute and chronic bronchial inflammation, gastrointestinal infections, etc. Due to the existence of two ester bonds and one lactone bond in the molecular structure of Yanhuning, its chemical stability is poor, and im...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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