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A kind of preparation method of Cyclovitamin D hydrochloride

A technology of cyclovir buxus and hydrochloride, which is applied in the field of medicine and chemical industry, can solve the problems of cumbersome column chromatography method, low yield, unsuitable for industrial production, etc. Effect

Active Publication Date: 2018-09-21
JIANGSU JINGLIXIN PHARMA TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although it is disclosed in the prior art that the use of column chromatography can improve the purity of cycloviribuxine D, the method of column chromatography is cumbersome and the yield is low, so it is not suitable for industrial production
In the prior art, there is a lack of simple, high-purity, high-yield cycloviribuxine D and its hydrochloride preparation method

Method used

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  • A kind of preparation method of Cyclovitamin D hydrochloride
  • A kind of preparation method of Cyclovitamin D hydrochloride
  • A kind of preparation method of Cyclovitamin D hydrochloride

Examples

Experimental program
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Effect test

Embodiment 1

[0038] Using the commercially available product of Cycloviral Buxusin D (Nanjing Shizhou Pharmaceutical Technology Co., Ltd.) as a raw material, the method disclosed in CN1594355A was used for refining to obtain the secondary crystal product of Cycloviral Buxusin D, and the purity was measured by TLC chromatographic system and HPLC respectively. .

[0039] TLC chromatographic system: thin-layer plate: silica gel G thin-layer plate; developer: chloroform: hexane: methanol: ammonia water = 2.5: 4: 1: 0.1; chromogen; dilute potassium iodide reagent; sample volume; 100 ~250 μg). The measurement results show that the TLC purity of the secondary crystalline product of Cyclovirubuxin D prepared by the method disclosed in CN1594355A is 96%.

[0040] HPLC system: Chromatographic column: Yuexu C18 (250mm×4.6mm, 5μm), mobile phase A: 0.01M sodium heptanesulfonate and 0.01M KH 2 PO 4 Equivalent mixed solution (containing 0.2% triethylamine, adjusted pH to 3.50 with phosphoric acid), mo...

Embodiment 2

[0047] Take the commercially available Huowei Buxus D, add 20 times the volume (W / V) of methanol, heat and stir until reflux (65°C), dissolve, and reflux for 15 minutes after dissolution, stop heating, slowly and naturally cool down, and stir to crystallize. Referring to this method, the crystallization was repeated four times to obtain four crystallization products. The mother liquor is used repeatedly, and after four times of crystallization, the yield reaches about 70%. The four crystallization results are as follows:

[0048] Table 3. Crystallization results of commercially available Cycloviral Buxicin D in methanol

[0049]

[0050] As shown in Table 3, the data in the table are the crude product and the 1st to 4th crystallization of the crude product in sequence. The first crystallization effect is particularly remarkable. The purity of Cyclovitamin D rose from 54.51% to 91.27%. However, the effect of the subsequent three crystallizations was not very signifi...

Embodiment 3

[0052] The tertiary crystalline product of Cyclovirubicin D in Example 2 is used as a raw material, as a sample to be formed into a salt, and its liquid phase purity is about 97%.

[0053] Get 30g of the third crystallization product of cyclovir buxicine D and divide it into three parts on average, dissolve them in 40 times of volume (W / V) water, 40 times of volume (W / V) methanol and 40 times of volume (W / V) methylene chloride, The salt-forming reaction was carried out at room temperature. Then add 2eq 1M dilute hydrochloric acid dropwise at room temperature and stir to form a salt. After water is used as solvent to form a salt, crystals cannot be precipitated or crystals are less at room temperature, and the temperature is lowered to about 4°C to crystallize; after methanol is used as a solvent to form a salt, the product and methanol are in the form of a paste, which is difficult to filter; Methane is used as a solvent. After the salt-forming reaction, the product is direct...

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Abstract

The invention provides a preparation method for cyclovirobuxinum D hydrochloride. The preparation method comprises the following steps: subjecting a crude product of cyclovirobuxinum D to recrystallization by using one or more selected from a group consisting of methanol, ethanol and chloroform; and dissolving a recrystallization product in an organic solvent, adding 1M dilute hydrochloric acid drop by drop, carrying out a reaction at room temperature for salt formation, then subjecting a precipitated salt to filtering and drying, then subjecting the dried salt and a mixed solvent of methanol and ethanol to heating reflux, and carrying out slow and natural cooling for crystallization after a solution is clear so as to obtain cyclovirobuxinum D hydrochloride. The preparation method provided by the invention is low in cost, simple to operate, easy to realize large-scale production, and high in yield, wherein the yield of the salt formation reaction is 90% or above; and the prepared cyclovirobuxinum D hydrochloride has HPLC purity of more than 99%.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and in particular relates to a method for preparing cyclovirboxine D hydrochloride with high purity and high yield. Background technique [0002] Cyclovirobuxine D (Cyclovirobuxine D) is an effective monomeric alkaloid extracted from Euonymus microphylla, which is a drug for treating neovascular diseases or a precursor for new drug development and can be widely used in the medical field. [0003] Studies have shown that Cycloviroxine D (Cyclobuxine), Cyclovirobuxine C (Cyclovirobxine) and Cyclovirobuxine, which are very similar in structure, are also contained in Cyclovirubuxine D obtained by traditional extraction and recrystallization methods. C (Cycloprotobuxine C) and other impurity components have a total impurity content of about 7-8%, and these impurities are difficult to remove by conventional means, and their purity is far from meeting the requirements of Cycloprotobuxine D ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J53/00
CPCC07J53/004
Inventor 朱雄张燕清
Owner JIANGSU JINGLIXIN PHARMA TECH CO LTD
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