CN101168537A - Method for simultaneously preparing andrographolide and dehydrated andrographolide - Google Patents
Method for simultaneously preparing andrographolide and dehydrated andrographolide Download PDFInfo
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- CN101168537A CN101168537A CNA2007101428007A CN200710142800A CN101168537A CN 101168537 A CN101168537 A CN 101168537A CN A2007101428007 A CNA2007101428007 A CN A2007101428007A CN 200710142800 A CN200710142800 A CN 200710142800A CN 101168537 A CN101168537 A CN 101168537A
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- rographolide
- deoxydidehydrorographolide
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Abstract
The invention relates to a method for simultaneously preparing andrographolide and didehydroandrographolide. The method includes that common andrographis herbs are smashed and then added into alcohol solvent with certain concentration to be abstracted, extracting solution is filtered, solvent is recycled to lead the concentration of the alcohol solvent in filtrate to be lower than 20 percent; after being filtered, the filtrate is taken to be exchanged through macroporous resin and to be absorbed, the alcohol solvent with certain concentration is used to operate the gradient elution, so as to lead the andrographolide and the didehydroandrographolide to be desorbed in elutriant with different concentration; after being concentrated, the elutriant is recrystallized and refined to obtain andrographolide crystal and didehydroandrographolide crystal. The purity degree of the two crystals obtained through the method reaches above 97 percent, and the method has the advantages that the process is simple, the operation is easy, the cost is low, the industrializing production can be operated, etc.
Description
Technical field
The present invention relates to a kind of method for preparing rographolide and deoxydidehydrorographolide of separating simultaneously, particularly relate to a kind of macroporous resin that utilizes and separate the method for preparing these two kinds of main effective constituents in the Herba Andrographis simultaneously.
Background technology
The main effective constituent of Herba Andrographis is the diterpenoid-lactone constituents, has effects such as antiphlogistic antibacterial, anti-virus infection.Wherein the highest with rographolide and deoxydidehydrorographolide content, and deoxydidehydrorographolide is to act on the strongest one in the rographolide compound.The medicine made from rographolide or deoxydidehydrorographolide and derivative thereof is as widespread uses clinically such as rographolide sheet, potasium dehydroandrographolisuccinate succinate injection, potassium sodium dehydroandroan drographolide succinate injection liquids.
The traditional technology of at present diterpenoid-lactone constituents in the Herba Andrographis being extracted has water to carry, buck is carried, sour water is carried, alcohol extracting etc.People such as Zhang Ling are according to rographolide in the extract and deoxydidehydrorographolide component content, draw impregnation technology＞diacolation technology＞warm soaking technology＞refluxing extraction technology, Heating temperature lactone composition in the time of 55 ℃ changes little, but long-time heating also can cause the structure deteriorate of lactonic ring.Because of the rographolide constituents is insoluble in water, the extraction efficiency and the content of water extraction are lower; And potass extraction method (CN1042077) is strict to the requirement of pH value, if the control of pH value is improper, might cause the hydrolysis of lactone, and active constituent content is all lower in the medicinal extract of these methods extractions.Pueraria lobota sends out joyous to wait the people to utilize supercritical CO
2Extraction process directly extracts the Herba Andrographis medicinal material, and the content of rographolide and deoxydidehydrorographolide is respectively 13.03% and 23.75% in the gained medicinal extract.In addition, people such as Fan Yunge have compared the technology of the non-polar macroporous resin absorption total andrographolide of 4 kinds of polystyrene types, and the content of total andrographolide is brought up to 25.3%.Chinese patent application CN1695702 discloses the Herba Andrographis ethanol extraction has been adopted inclusion and the method for the supermolecule extract effective constituent that removes enclose, rographolide and deoxydidehydrorographolide content reach 40.41% and 10.20% respectively in its supramolecular extractive, compare with routine techniques, content improves greatly.
The rographolide deoxydidehydrorographolide
Though above-mentioned technology makes the content of rographolide constituents in extract obtain raising in various degree, does not prepare the highly purified crystallization of rographolide or deoxydidehydrorographolide monomeric compound or these two kinds of compositions yet.Chinese patent application CN1935798A discloses a kind of preparation method of rographolide, has prepared highly purified rographolide by this method, does not connect lactone but prepare the dehydration punching simultaneously.And the alcoholic solvent that the present invention adopts different concns connects lactone and carries out desorb respectively being adsorbed on rographolide on the macroporous resin and dehydration punching, again in conjunction with recrystallization technology, can prepare rographolide simultaneously and connect two kinds of crystallizations of lactone with the dehydration punching, medicinal material utilization ratio and product yield have not only been improved, reduced waste, have also simultaneously that technology is simple, easy to operate, cost is low, can suitability for industrialized production etc. outstanding advantage.
Summary of the invention
The object of the present invention is to provide a kind of method for preparing rographolide and deoxydidehydrorographolide simultaneously, these two kinds of crystalline purity that obtain by this method all can reach more than 97%, and this method has that technology is simple, easy to operate, cost is low, can suitability for industrialized production etc. outstanding advantage.
Purpose of the present invention can realize by implementing following technical proposals:
The method for preparing rographolide and deoxydidehydrorographolide simultaneously provided by the invention, carry out according to the following steps:
1. solvent extraction: extract with adding certain density alcoholic solvent in the Herba Andrographis pulverizing back:
Described solvent comprises water, ethanol, methyl alcohol; Wherein solvent mixes with the Herba Andrographis grass, count 1: 3 by weight～and 30; Described solvent can be a kind of solvent, or the mixed solvent of arbitrary proportion, and wherein preferred determining alcohol is 40～60%; Described extracting method is cold soaking or supersound extraction.
2. behind the extracting liquid filtering that step 1 is obtained, reclaim solvent, make that alcoholic solvent concentration is lower than 20% in the filtrate; After refiltering, get filtrate flow and exchange, adsorb through macroporous resin column, its flow velocity is 0.8～3BV/h;
3. finish through step 2 exchange, absorption, the alcoholic solvent of water and different concns from low to high carries out gradient elution as elutriant respectively.Elder generation's water or be lower than 35% alcoholic solvent the high polar impurity of major part wash-out is removed, with 35～50% alcoholic solvent rographolide is eluted and collects then, with 55～100% alcoholic solvent deoxydidehydrorographolide is eluted and collects again, contrast the starting point that elutriant is collected in decision by silica-gel plate thin-layer chromatography and rographolide and deoxydidehydrorographolide standard substance, thus the elutriant of the rographolide that obtained enrichment respectively and deoxydidehydrorographolide.
4. will be through enrichment that step 3 obtains after the elutriant of rographolide and deoxydidehydrorographolide concentrates respectively, the utilization recrystallization technology is refining to be obtained purity and can reach rographolide and deoxydidehydrorographolide crystallization more than 97%.
Other detail are common in this area.
Embodiment
Embodiment 1:
After 50g Herba Andrographis herb was pulverized, its particle diameter reached 4mm, added 150mL 50% aqueous ethanolic solution and mixed, and dipping extracts 3 times, extracts respectively 3,2,1 days.Extracting liquid filtering decompression and solvent recovery to rographolide still is in dissolved state, adding water dilutes in right amount, filter or the centrifugal precipitation that discards, with the nonpolar DA201-A macroporous resin that filtrate is produced by Chemical Plant of Nankai Univ., filtrate is 3mL/min through the flow velocity of resin column exchange, absorption; After exchange finishes, difference water, 35%, 45%, 55%, 60% ethanol elution, elution process contrasts the starting point that elutriant is collected in decision with silica-gel plate thin-layer chromatography and rographolide and deoxydidehydrorographolide standard substance, high performance liquid chromatograph detects rographolide and deoxydidehydrorographolide content in the elutriant, mainly contain rographolide in 45% ethanol eluate, content is 46.99%, filter the back recrystallization with 80% ethanol water dissolution, obtain rographolide crystal 0.255g, purity reaches 97.8%; Mainly contain deoxydidehydrorographolide in 55% ethanol eluate, content is 79.74%, filters the back recrystallization with 80% ethanol water dissolution, obtains crystal 0.039g, and purity reaches 98.6%.
The exhausted resin column is then with can using repeatedly behind 10% alcohol flushing, but the ethanol reclaim under reduced pressure.Adopt content that present method makes rographolide 3.6% to bring up to 46% after the macroporous resin enrichment before the last sample, the rate of recovery is 98%; The content of deoxydidehydrorographolide brings up to 79% from 0.6%, and the rate of recovery is 97%.
Embodiment 2:
After 50g Herba Andrographis herb was pulverized, its particle diameter reached 5mm, in the extractor of packing into, added 200mL 50% aqueous ethanolic solution and mixed, and mixing solutions was placed in the ultrasonic generator container then, with ultrasonic wave the Herba Andrographis grass meal was carried out supersound extraction.Used ultrasonic frequency is 20KHz, and power is 50W～10000W, and the supersound extraction time is 60 minutes, and temperature is 40 degree.Extracting liquid filtering decompression and solvent recovery to rographolide still is in dissolved state, adding water dilutes in right amount, filter or the centrifugal precipitation that discards, with the nonpolar DA201-B macroporous resin that filtrate is produced by Chemical Plant of Nankai Univ., filtrate is 3mL/min through the flow velocity of resin column exchange, absorption; After exchange finishes, difference water, 30%, 50%, 70%, 90% wash-out, elution process contrasts the starting point that elutriant is collected in decision with silica-gel plate thin-layer chromatography and rographolide and deoxydidehydrorographolide standard substance, high performance liquid chromatograph detects rographolide and deoxydidehydrorographolide content in the elutriant, mainly contain rographolide in 50% ethanol eluate, content is 48.39%, filter the back recrystallization with 80% ethanol water dissolution, obtain rographolide crystal 0.245g, purity reaches 97.8%; Mainly contain deoxydidehydrorographolide in 70% ethanol eluate, content is 80.23%, filters the back recrystallization with 80% ethanol water dissolution, obtains crystal 0.037g, and purity reaches 98.4%.
The exhausted resin column is then with can using repeatedly behind 10% alcohol flushing, but the ethanol reclaim under reduced pressure.Adopt content that present method makes rographolide before the last sample 4.2% bring up to after the macroporous resin enrichment more than 48%, the rate of recovery is 96%; The content of deoxydidehydrorographolide is brought up to more than 80% from 0.57%, and the rate of recovery is 95%.
Embodiment 3:
After 50g Herba Andrographis herb was pulverized, its particle diameter reached 2mm, added 250mL 60% aqueous ethanolic solution and mixed, and dipping extracts 3 times, extracts respectively 3,2,1 days.Extracting liquid filtering decompression and solvent recovery to rographolide still is in dissolved state, adding water dilutes in right amount, filter or the centrifugal precipitation that discards, with the nonpolar DA201-B macroporous resin that filtrate is produced by Chemical Plant of Nankai Univ., filtrate is 3mL/min through the flow velocity of resin column exchange, absorption; After exchange finishes, difference water, 30%, 45%, 60%, 70% ethanol elution, elution process contrasts the starting point that elutriant is collected in decision with silica-gel plate thin-layer chromatography and rographolide and deoxydidehydrorographolide standard substance, high performance liquid chromatograph detects rographolide and deoxydidehydrorographolide content in the elutriant, mainly contain rographolide in 45% ethanol eluate, content is 48.57%, 80% ethanol water dissolution is filtered the back recrystallization, obtain rographolide crystal 0.252g, purity reaches 98.8%; Mainly contain deoxydidehydrorographolide in 60% ethanol eluate, content is that 78.48%, 80% ethanol water dissolution is filtered the back recrystallization, obtains crystal 0.038g, and purity reaches 99.3%.
The exhausted resin column is then with can using repeatedly behind 10% alcohol flushing, but the ethanol reclaim under reduced pressure.Adopt content that present method makes rographolide before the last sample 4.1% bring up to after the macroporous resin enrichment more than 48%, the rate of recovery is 97%; The content of deoxydidehydrorographolide is brought up to more than 78% from 0.63%, and the rate of recovery is 97%.
Embodiment 4:
After 50g Herba Andrographis herb was pulverized, its particle diameter reached 5mm, in the extractor of packing into, added 200mL 70% aqueous ethanolic solution and mixed, and mixing solutions was placed in the ultrasonic generator container then, with ultrasonic wave the Herba Andrographis grass meal was carried out supersound extraction.Used ultrasonic frequency is 20KHz, and power is 50W～10000W, and the supersound extraction time is 60 minutes, and temperature is 45 degree.Extracting liquid filtering decompression and solvent recovery to rographolide still is in dissolved state, adding water dilutes in right amount, filter or the centrifugal precipitation that discards, with the nonpolar DA201-C macroporous resin that filtrate is produced by Chemical Plant of Nankai Univ., filtrate is 3mL/min through the flow velocity of resin column exchange, absorption; After exchange finishes, difference water, 30%, 40%, 45%, 50%, 55%, 60% ethanol elution, elution process contrasts the starting point that elutriant is collected in decision with silica-gel plate thin-layer chromatography and rographolide and deoxydidehydrorographolide standard substance, high performance liquid chromatograph detects rographolide and deoxydidehydrorographolide content in the elutriant, mainly contain rographolide in 45% ethanol eluate, content is 46.17%, filter the back recrystallization with 80% ethanol water dissolution, obtain rographolide crystal 0.255g, purity reaches 97.6%; Mainly contain deoxydidehydrorographolide in 55% ethanol eluate, content is 81.62%, filters the back recrystallization with 80% ethanol water dissolution, obtains crystal 0.039g, and purity reaches 99.7%.
The exhausted resin column is then with can using repeatedly behind 10% alcohol flushing, but the ethanol reclaim under reduced pressure.Adopt content that present method makes rographolide 4.8% to bring up to more than 46% of macroporous resin enrichment before the last sample, the rate of recovery is 98%; The content of deoxydidehydrorographolide is brought up to more than 81% from 0.6%, and the rate of recovery is 96%.
Claims (7)
1. method for preparing rographolide and deoxydidehydrorographolide simultaneously is characterized in that carrying out according to the following steps:
(1) solvent extraction: extract with adding certain density alcoholic solvent in the Herba Andrographis pulverizing back;
(2) with behind the extracting liquid filtering, reclaim solvent, make that alcoholic solvent concentration is lower than 20% in the filtrate; After refiltering, get filtrate flow and exchange, adsorb through macroporous resin column, its flow velocity is 0.8～3BV/h;
(3) finish through resins exchange, absorption, carry out gradient elution as elutriant, make rographolide and deoxydidehydrorographolide distinguish desorb in the elutriant of different concns with the alcoholic solvent of different concns;
(4) elutriant that contains rographolide and deoxydidehydrorographolide is respectively suitably concentrated after, carry out recrystallization, refiningly obtain rographolide and deoxydidehydrorographolide crystallization.
2. according to the described method for preparing rographolide and deoxydidehydrorographolide simultaneously of claim 1, it is characterized in that: the solvent that uses in the described step 1 comprises water, ethanol, methyl alcohol; Wherein solvent mixes with the Herba Andrographis medicinal material coarse powder, count 1: 3 by weight～and 30.
3. according to the described method for preparing rographolide and deoxydidehydrorographolide simultaneously of claim 1, it is characterized in that: the solvent that uses in the described step 1 can be a kind of solvent, or the mixed solvent of arbitrary proportion, wherein preferred determining alcohol is 40～60%.
4. according to the described method for preparing rographolide and deoxydidehydrorographolide simultaneously of claim 1, it is characterized in that: the extracting method that adopts in the described step 1 can be that cold soaking extracts, or supersound extraction, wherein cold soaking extraction time is 1～15d, the supersound extraction time is 30min～120min.
5. according to the described method for preparing rographolide and deoxydidehydrorographolide simultaneously of claim 1, it is characterized in that: the solvent that uses in the described step 3 comprises water, ethanol, methyl alcohol.
6. according to the described method for preparing rographolide and deoxydidehydrorographolide simultaneously of claim 1, it is characterized in that: be used for the elutriant of the rographolide of desorb resin in the described step 3, the concentration of its alcoholic solvent is 35～50%; The elutriant that is used for the deoxydidehydrorographolide of desorb resin, the concentration of its alcoholic solvent are 55～100%.
7. according to the described method for preparing rographolide and deoxydidehydrorographolide simultaneously of claim 1, it is characterized in that: described macroporous resin model is DA201-A, B, C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007101428007A CN101168537A (en) | 2007-07-06 | 2007-07-06 | Method for simultaneously preparing andrographolide and dehydrated andrographolide |
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| CNA2007101428007A CN101168537A (en) | 2007-07-06 | 2007-07-06 | Method for simultaneously preparing andrographolide and dehydrated andrographolide |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102432568A (en) * | 2010-09-29 | 2012-05-02 | 无锡济民可信山禾药业股份有限公司 | Method for preparing andrographolidume by utilizing adsorption method |
| CN101559088B (en) * | 2009-05-21 | 2012-07-25 | 雷允上药业有限公司 | Production technique of andrographolide and neoandrographolide, dehydroanddrographolide, oxyandrographolide |
| CN103145661A (en) * | 2013-03-25 | 2013-06-12 | 成都天台山制药有限公司 | New crystal form of andrographolide |
| CN103664842A (en) * | 2013-12-16 | 2014-03-26 | 无锡济民可信山禾药业股份有限公司 | Continuous chromatographic separation method for andrographolide |
| CN104311515A (en) * | 2014-09-04 | 2015-01-28 | 桂林甙元生物科技有限公司 | Separation and extraction technology of andrographolide and dehydroandrographolide |
| CN104557818A (en) * | 2014-12-16 | 2015-04-29 | 浙江维康药业有限公司 | Common andrographis herb lactone compound as well as dropping pills and soft capsules containing compound |
| CN105884722A (en) * | 2016-04-27 | 2016-08-24 | 聊城大学 | Method of separating and purifying andrographolide and dehydrated andrographolide from Herba andrographitis |
| CN114634470A (en) * | 2022-03-25 | 2022-06-17 | 太极集团四川南充制药有限公司 | Extraction method of dehydroandrographolide and andrographis tablet |
-
2007
- 2007-07-06 CN CNA2007101428007A patent/CN101168537A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101559088B (en) * | 2009-05-21 | 2012-07-25 | 雷允上药业有限公司 | Production technique of andrographolide and neoandrographolide, dehydroanddrographolide, oxyandrographolide |
| CN102432568A (en) * | 2010-09-29 | 2012-05-02 | 无锡济民可信山禾药业股份有限公司 | Method for preparing andrographolidume by utilizing adsorption method |
| CN102432568B (en) * | 2010-09-29 | 2015-04-22 | 无锡济民可信山禾药业股份有限公司 | Method for preparing andrographolidume by utilizing adsorption method |
| CN103145661A (en) * | 2013-03-25 | 2013-06-12 | 成都天台山制药有限公司 | New crystal form of andrographolide |
| CN103145661B (en) * | 2013-03-25 | 2014-06-18 | 成都天台山制药有限公司 | New crystal form of andrographolide |
| CN103664842A (en) * | 2013-12-16 | 2014-03-26 | 无锡济民可信山禾药业股份有限公司 | Continuous chromatographic separation method for andrographolide |
| CN104311515A (en) * | 2014-09-04 | 2015-01-28 | 桂林甙元生物科技有限公司 | Separation and extraction technology of andrographolide and dehydroandrographolide |
| CN104311515B (en) * | 2014-09-04 | 2017-01-25 | 桂林甙元生物科技有限公司 | Separation and extraction technology of andrographolide and dehydroandrographolide |
| CN104557818A (en) * | 2014-12-16 | 2015-04-29 | 浙江维康药业有限公司 | Common andrographis herb lactone compound as well as dropping pills and soft capsules containing compound |
| CN105884722A (en) * | 2016-04-27 | 2016-08-24 | 聊城大学 | Method of separating and purifying andrographolide and dehydrated andrographolide from Herba andrographitis |
| CN105884722B (en) * | 2016-04-27 | 2018-03-13 | 聊城大学 | A kind of method that andrographolide and Dehydro and drographolide are isolated and purified from Herba Andrographitis |
| CN114634470A (en) * | 2022-03-25 | 2022-06-17 | 太极集团四川南充制药有限公司 | Extraction method of dehydroandrographolide and andrographis tablet |
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