CN111217822A - Preparation method of tetrandrine as Chinese medicinal anti-allergy agent - Google Patents
Preparation method of tetrandrine as Chinese medicinal anti-allergy agent Download PDFInfo
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- CN111217822A CN111217822A CN202010170177.1A CN202010170177A CN111217822A CN 111217822 A CN111217822 A CN 111217822A CN 202010170177 A CN202010170177 A CN 202010170177A CN 111217822 A CN111217822 A CN 111217822A
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- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
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Abstract
The invention discloses a preparation method of tetrandrine as a traditional Chinese medicine anti-allergy agent, which comprises the following steps: s1, extracting total alkaloids, collecting Stephania tetrandra powder 100g, placing in 500ml round bottom flask, adding ethanol 300ml, heating in water bath and refluxing for 1 hr, filtering to obtain ethanol extract, extracting the residue with ethanol 200ml for 1 time, mixing the two extracts, filtering, concentrating to remove ethanol smell, and making into syrup to obtain total alkaloids. The invention utilizes multiple solvent additions to prepare the main components in the tetrandrine powder according to total alkaloids, total alkaloids of tetrandrine and mixed crystals, and obtains tetrandrine and tetrandrine respectively after two liquid-liquid extractions of target components by mutual superposition operation between filtration and extraction and by adjusting the pH of materials in corresponding steps, and then separates the two components through solubility difference, thereby effectively improving the utilization rate of raw materials and reducing the production cost.
Description
Technical Field
The invention relates to the technical field of tetrandrine preparation, in particular to a preparation method of tetrandrine serving as a traditional Chinese medicine anti-allergy agent.
Background
Tetrandrine is a bisbenzylisoquinoline alkaloid extracted from the root tuber of the traditional Chinese medicine tetrandrine, is a high-purity extract extracted from herbal medicines, plays a role in easing pain by reducing peroxide release and phagocytic activity, can increase the accumulation of chemotherapeutic drugs in tumor cells and enhance the sensitivity of the tumor cells to the chemotherapeutic drugs by inhibiting the over-expression function of P-glycoprotein on the surface of tumor drug-resistant cells, can be clinically used for rheumatalgia, arthralgia and neuralgia, is combined with small-dose radiation for lung cancer, and can be used for patients in need of worrying under the guidance of doctors.
At present, the process for extracting tetrandrine and tetrandrine (see handbook for extracting and separating chemical components of traditional Chinese medicine, P130-133, compiled by Yang Yun and Von health Main); the Chinese patent (application number 200710056757.2) adsorption resin method for separating the monomeric alkaloid in the tetrandrine total alkaloid has the following problems: benzene is used as a purification solvent to remove the hanfangchin B in the purification process, so that a finished product has residues and potential harm is caused to the production environment and operators; hanfangchin A and hanfangchin B can not be obtained simultaneously; the subsequent separation of the tetrandrine and tetrandrine is not thorough, and the quality of the tetrandrine product is influenced.
Disclosure of Invention
Based on the technical problems in the background art, the invention provides a preparation method of tetrandrine which is a traditional Chinese medicine anti-allergy agent.
The invention provides a preparation method of tetrandrine as a traditional Chinese medicine anti-allergy agent, which is characterized by comprising the following steps:
s1: extracting total alkaloids: taking 100g of tetrandra powder, placing into a 500ml round bottom flask, adding 300ml of ethanol, heating and refluxing for 1 hour in a water bath, filtering out an ethanol extracting solution, adding 200ml of ethanol again into dregs of a decoction, extracting for 1 time by the same method, combining the two extracting solutions, filtering, concentrating until no alcohol smell exists, and forming into syrup to obtain total alkaloids;
s2: extracting tetrandrine: transferring the alkaloid extractive solution into a beaker, adding 1% hydrochloric acid to adjust pH to 2, heating while stirring, standing, and filtering to obtain clear filtrate; adding equal volume of chloroform into the filtrate, adding ammonia water to adjust pH to above 10, shaking and extracting in a separating funnel, standing for layering, discharging chloroform layer, extracting alkali liquor with chloroform twice, and mixing chloroform solutions; placing the chloroform solution in a separating funnel, washing with 1% sodium hydroxide solution for 2 times, washing with water for 2-3 times, adding about 5g anhydrous sodium sulfate for dehydration, standing overnight, filtering, and recovering chloroform to a small amount to obtain tetrandrine;
s3: extracting tetrandrine and tetrandrine crystal: the tetrandrine and tetrandrine crystal is obtained through the following four steps, and specifically comprises the following contents:
1) loading the column, vertically fixing the chromatographic column on an iron support, filling a small amount of cotton into the lower end of the tube, weighing 100-mesh 20g of neutral alumina, slowly adding the neutral alumina into the chromatographic column, and gently vibrating the chromatographic column while adding the neutral alumina into the chromatographic column to ensure that the alumina is uniformly filled in the column.
2) Loading 100mg of total tetrandrine into a small evaporating dish, dissolving with small amount of acetone, adding 0.5g of chromatographic alumina, stirring, and slowly evaporating in water bath to remove solvent. The alumina containing sample was then loaded into the upper end of the column and covered with a round filter paper.
3) Elution the column piston was opened and eluted with cyclohexane-acetone (4: 1).
4) Checking, recovering solvent from each fraction, sequentially dropping on silica gel G-CMC-Na thin layer plate, developing with chloroform-acetone-methanol (6:1:1) as developer, spraying improved bismuth potassium iodide reagent, comparing Rf values of each fraction, and combining the fractions with the same Rf value.
5) And (4) concentrating the solution of the combined fractions to a proper volume, standing for crystallization, and dropwise adding a small amount of acetone to wash and crystallize to obtain tetrandrine and tetrandrine crystals.
S4: and (3) mixed crystal identification: the obtained tetrandrine is sampled and crushed into 100-mesh small particles, and then the particles are detected by chemical detection and chromatography.
S5: separation of tetrandrine and tetrandrine in tetrandrine: the tetrandrine can be dissolved in cold benzene, and the tetrandrine is insoluble in cold benzene, and can be obtained by separating cold benzene from tetrandrine and cold benzene.
As a further embodiment of the present invention, the ethanol solution used in S1 has a volume concentration of 85%.
As a further scheme of the invention, the dosage of the 1% hydrochloric acid solution in the S2 is 80ml-100 ml.
As a further scheme of the invention, 1% hydrochloric acid is added into the S2 to adjust the pH value, and the mixture is heated and stirred in a water bath at 50 ℃.
In a further embodiment of the present invention, in the step of eluting in S3, the elution flow rate is controlled at 5ml/min, and each fraction is collected at 10 ml/part to 15 ml/part.
As a further scheme of the present invention, the separation basis of tetrandrine and fangchinoline in tetrandrine in S5 is due to the difference of 7-position substituent in the molecular structures of the two, the former is methoxy and has small polarity; the latter is phenolic hydroxyl and has high polarity.
The beneficial effects of the invention are as follows:
1. the preparation method comprises the steps of adding a solvent for multiple times, preparing main components in tetrandrine powder according to total alkaloids, total alkaloids of hanfang hexi and mixed crystals, and performing liquid-liquid extraction twice on target components by performing mutual superposition operation between filtration and extraction and adjusting the pH of materials in corresponding steps to obtain tetrandrine and tetrandrine respectively;
2. the preparation method does not use benzene in the extraction, reduces the potential harm of the production process to the environment and operators, effectively avoids the solvent residue of benzene, can simultaneously obtain two products of the tetrandrine and the tetrandrine, and then separates the two products through the solubility difference, effectively improves the utilization rate of raw materials and reduces the production cost.
Drawings
FIG. 1 is a general flow chart of the preparation method of tetrandrine, a traditional Chinese medicine anti-allergy agent, provided by the invention;
FIG. 2 is a flow chart of the preparation process of tetrandrine, a Chinese medicinal anti-allergic agent, in example 1;
fig. 3 is a preparation flow chart of the preparation method of tetrandrine, a traditional Chinese medicine anti-allergy agent, provided by the invention in example 2.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.
Example 1
Referring to fig. 1-2, a method for preparing tetrandrine, a traditional Chinese medicine anti-allergy agent, comprises the following steps:
s1: extracting total alkaloids: taking 100g of tetrandra powder, placing into a 500ml round bottom flask, adding 300ml of ethanol, heating and refluxing for 1 hour in a water bath, filtering out an ethanol extracting solution, adding 200ml of ethanol again into dregs of a decoction, extracting for 1 time by the same method, combining the two extracting solutions, filtering, concentrating until no alcohol smell exists, and forming into syrup to obtain total alkaloids;
s2: extracting tetrandrine: transferring the alkaloid extractive solution into a beaker, adding 1% hydrochloric acid to adjust pH to 2, heating while stirring, standing, and filtering to obtain clear filtrate; adding equal volume of chloroform into the filtrate, adding ammonia water to adjust pH to above 10, shaking and extracting in a separating funnel, standing for layering, discharging chloroform layer, extracting alkali liquor with chloroform twice, and mixing chloroform solutions; placing the chloroform solution in a separating funnel, washing with 1% sodium hydroxide solution for 2 times, washing with water for 2-3 times, adding about 5g anhydrous sodium sulfate for dehydration, standing overnight, filtering, and recovering chloroform to a small amount to obtain tetrandrine;
s3: extracting tetrandrine and tetrandrine crystal: the tetrandrine and tetrandrine crystal is obtained through the following four steps, and specifically comprises the following contents:
1) loading the column, vertically fixing the chromatographic column on an iron support, filling a small amount of cotton into the lower end of the tube, weighing 100-mesh 20g of neutral alumina, slowly adding the neutral alumina into the chromatographic column, and gently vibrating the chromatographic column while adding the neutral alumina into the chromatographic column to ensure that the alumina is uniformly filled in the column.
2) Loading 100mg of total tetrandrine into a small evaporating dish, dissolving with small amount of acetone, adding 0.5g of chromatographic alumina, stirring, and slowly evaporating in water bath to remove solvent. The alumina containing sample was then loaded into the upper end of the column and covered with a round filter paper.
3) Elution the column piston was opened and eluted with cyclohexane-acetone (4: 1).
4) Checking, recovering solvent from each fraction, sequentially dropping on silica gel G-CMC-Na thin layer plate, developing with chloroform-acetone-methanol (6:1:1) as developer, spraying improved bismuth potassium iodide reagent, comparing Rf values of each fraction, and combining the fractions with the same Rf value.
5) And (4) concentrating the solution of the combined fractions to a proper volume, standing for crystallization, and dropwise adding a small amount of acetone to wash and crystallize to obtain tetrandrine and tetrandrine crystals.
S4: and (3) mixed crystal identification: the obtained tetrandrine is sampled and crushed into 100-mesh small particles, and then the particles are detected by chemical detection and chromatography.
S5: separation of tetrandrine and tetrandrine in tetrandrine: the tetrandrine can be dissolved in cold benzene, and the tetrandrine is insoluble in cold benzene, and can be obtained by separating cold benzene from tetrandrine and cold benzene.
Wherein the volume concentration of the ethanol solution used in S1 is 85%; the dosage of the 1% hydrochloric acid solution in the S2 is 80ml-100 ml; adding 1% hydrochloric acid to adjust pH, heating in 50 deg.C water bath, and stirring; in the elution step, the elution flow rate is controlled at 5ml/min, and 10mI-15 mI/part of each fraction is collected; the separation of tetrandrine and tetrandrine in tetrandrine is based on the difference of 7-position substituent in the molecular structures of the tetrandrine and the tetrandrine, wherein the former is methoxyl and has small polarity; the latter is phenolic hydroxyl and has high polarity.
Example 2
Referring to fig. 3, a method for preparing tetrandrine, which is a traditional Chinese medicine anti-allergic agent, is mainly different from example 1 in that cyclohexane-ethyl acetate (1: 3) is used to replace cyclohexane-acetone (4:1) for elution, wherein ethyl acetate can be decomposed after remaining in subsequent elution, and a developing agent which is replaced subsequently, cyclohexane: ethyl acetate: the dissolving effect in diethylamine (6: 2: 1) is better, the residue is reduced, and simultaneously, acetone is a toxic substance, which affects the subsequent quality.
Meanwhile, when the tetrandrine and the tetrandrine are separated from the tetrandrine, the mixture of the tetrandrine and the tetrandrine is dissolved in a proper amount of diluted acid water, the tetrandrine is extracted by benzene after alkalization, and then the tetrandrine is extracted by chloroform, so that the cold benzene is replaced and separated by utilizing the solubility difference, and the tetrandrine in the tetrandrine are separated by utilizing the polarity difference of the tetrandrine and the tetrandrine, so that the separation by utilizing the diluted acid water is safer and more effective.
In the preparation method of the tetrandrine which is a traditional Chinese medicine anti-allergy agent, the chemical detection and the chromatographic detection in the detection specifically comprise the following steps:
1) chemical identification
Extracting the extracted chloroform solution with 1% hydrochloric acid to obtain 10 ml of hydrochloric acid solution, dividing into four small test tubes for storage, adding modified bismuth potassium iodide, iodine-potassium iodide, mercury potassium iodide and silicotungstic acid reagents into the four small test tubes respectively, observing the change in each test tube, and recording in the following table.
2) Chromatography assay
Chromatography material silica gel G-CM-Na hard plate
Sample application is carried out by 0.1% alcoholic solution of tetrandrine, tetrandrine and tetrandrine
Developing agent:
(1): chloroform-acetone-methanol (6:1:1)
② chloroform-ethanol (10:1)
③ toluene-acetone-ethanol (4:5:1), developer, modified bismuth potassium iodide reagent
And (4) observing and recording: the spectrum and spot color were recorded.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (6)
1. A preparation method of tetrandrine which is a traditional Chinese medicine anti-allergy agent is characterized by comprising the following steps:
s1: extracting total alkaloids: taking 100g of tetrandra powder, placing into a 500ml round bottom flask, adding 300ml of ethanol, heating and refluxing for 1 hour in a water bath, filtering out an ethanol extracting solution, adding 200ml of ethanol again into dregs of a decoction, extracting for 1 time by the same method, combining the two extracting solutions, filtering, concentrating until no alcohol smell exists, and forming into syrup to obtain total alkaloids;
s2: extracting tetrandrine: transferring the total alkaloid extract into a beaker, adding 1% hydrochloric acid to adjust pH to 2, heating while stirring, standing, and filtering to obtain clear filtrate; adding equal volume of chloroform into the filtrate, adding ammonia water to adjust pH to above 10, shaking and extracting in a separating funnel, standing for layering, discharging chloroform layer, extracting alkali liquor with chloroform twice, and mixing chloroform solutions; placing the chloroform solution in a separating funnel, washing with 1% sodium hydroxide solution for 2 times, washing with water for 2-3 times, adding about 5g anhydrous sodium sulfate for dehydration, standing overnight, filtering, and recovering chloroform to a small amount to obtain tetrandrine;
s3: extracting tetrandrine and tetrandrine crystal: the tetrandrine and tetrandrine crystal is obtained through the following four steps, and specifically comprises the following contents:
1. loading a column, vertically fixing a chromatographic column on an iron support, filling a small amount of cotton at the lower end of the tube, weighing 100-mesh 20g of neutral alumina, slowly adding the neutral alumina into the chromatographic column, and slightly vibrating the chromatographic column while adding the neutral alumina into the chromatographic column so as to uniformly fill the alumina in the column;
2. loading 100mg of tetrandrine total alkali into a small evaporation dish, dissolving with a small amount of acetone, adding 0.5g of alumina for chromatography, stirring, slowly evaporating in water bath to remove solvent, loading the alumina containing sample into the upper end of a chromatographic column, and covering with a round filter paper;
3. elution the column piston was opened and eluted with cyclohexane-acetone (4: 1);
4. checking and recovering solvent from each fraction, sequentially dropping on silica gel G-CMC-Na thin layer plate, developing with chloroform-acetone-methanol (6:1:1) as developer, spraying improved bismuth potassium iodide reagent, comparing Rf values of each fraction, and combining fractions with the same Rf value;
5. crystallizing, concentrating the solution of the combined fractions to appropriate volume, standing for crystallization, and dropwise adding a small amount of acetone to wash and crystallize to obtain tetrandrine and tetrandrine crystals;
s4: and (3) mixed crystal identification: sampling and crushing the obtained tetrandrine body into small particles of 100 meshes, and then carrying out chemical identification and chromatographic identification;
s5: separation of tetrandrine and tetrandrine in tetrandrine: the tetrandrine can be dissolved in cold benzene, and the tetrandrine is insoluble in cold benzene, and can be obtained by separating cold benzene from tetrandrine and cold benzene.
2. The method for preparing tetrandrine, a Chinese medicinal anti-allergy agent, according to claim 1, wherein the volume concentration of the ethanol solution used in S1 is 85%.
3. The method for preparing tetrandrine, a Chinese medicinal anti-allergy agent, according to claim 1, wherein the amount of the 1% hydrochloric acid solution in S2 is 80ml-100 ml.
4. The method for preparing tetrandrine, an anti-allergic agent of traditional Chinese medicine, as claimed in claim 1, wherein 1% hydrochloric acid is added to S2 to adjust pH, and heating and stirring are carried out in water bath at 50 ℃.
5. The method for preparing tetrandrine, an anti-allergic agent of traditional Chinese medicine, as claimed in claim 1, wherein in the step of S3, the flow rate of elution is controlled at 5ml/min, and each fraction is collected at 10-15 ml/part.
6. The method for preparing tetrandrine as an anti-allergic agent in Chinese medicine according to claim 1, wherein the separation of tetrandrine and fangchinoline from tetrandrine in S5 is based on the difference of 7-position substituent in the molecular structures of the tetrandrine and fangchinoline, the former is methoxy and has small polarity; the latter is phenolic hydroxyl and has high polarity.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114515305A (en) * | 2021-12-27 | 2022-05-20 | 上海柒色生物科技有限公司 | Plant-derived composition for relieving skin inflammation of infants and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850824A (en) * | 2006-04-27 | 2006-10-25 | 富力 | Benzene-free tetrandrine and its preparing method |
| CN1903856A (en) * | 2006-08-03 | 2007-01-31 | 西安皓天生物工程技术有限责任公司 | Preparation method of Tetrandrine and Fangchino-kine |
| CN101012229A (en) * | 2007-01-26 | 2007-08-08 | 北海阳光药业有限公司 | Hanfangchin A without benzene and chloroform and preparing method thereof |
-
2020
- 2020-03-12 CN CN202010170177.1A patent/CN111217822A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1850824A (en) * | 2006-04-27 | 2006-10-25 | 富力 | Benzene-free tetrandrine and its preparing method |
| CN1903856A (en) * | 2006-08-03 | 2007-01-31 | 西安皓天生物工程技术有限责任公司 | Preparation method of Tetrandrine and Fangchino-kine |
| CN101012229A (en) * | 2007-01-26 | 2007-08-08 | 北海阳光药业有限公司 | Hanfangchin A without benzene and chloroform and preparing method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114515305A (en) * | 2021-12-27 | 2022-05-20 | 上海柒色生物科技有限公司 | Plant-derived composition for relieving skin inflammation of infants and preparation method and application thereof |
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Application publication date: 20200602 |