CN104530181A - Method for preparing tanshinone II A - Google Patents
Method for preparing tanshinone II A Download PDFInfo
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- CN104530181A CN104530181A CN201410808695.6A CN201410808695A CN104530181A CN 104530181 A CN104530181 A CN 104530181A CN 201410808695 A CN201410808695 A CN 201410808695A CN 104530181 A CN104530181 A CN 104530181A
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- tanshinone
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/003—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by oxygen as hetero atom
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- General Health & Medical Sciences (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a method for preparing tanshinone II A. The method comprises the following main steps: performing heat reflux extraction on salvia miltiorrhiza by using ethanol, performing column chromatography separation on a macroporous resin, collecting the eluent, performing vacuum concentration, performing vacuum drying, recrystallizing, thereby obtaining the tanshinone II A. According to the preparation method disclosed by the invention, the yield and purity of the tanshinone II A are high, and the method is easy to operate and low in cost and has a certain application values.
Description
Technical field
The invention belongs to Chemistry for Chinese Traditional Medicine field, be specifically related to a kind of tanshinone IIA preparation method.
Background technology
The red sage root has another name called red ginseng, Radix Salviae Miltiorrhizae, red etc.For Lamiaceae Salvia belongs to the dry root and rhizome of the per nnial herb red sage root.The red sage root as traditional Chinese medicine simply in China's application for a long time, begins to be loaded in Shennong's Herbal, is listed in top grade, mainly contains effect of stasis-dispelling and pain-killing, promoting blood circulation to restore menstrual flow, the relieving restlessness that clears away heart-fire, nourishing blood to tranquillize the mind.
The red sage root is mainly containing two active components: one is fat-soluble diterpene-kind compound, and one is water miscible poly liposoluble ingredient.Water soluble component take salvianolic acid B as representative, and fat-soluble component is tanshinone, mainly contains Tanshinone I, tanshinone IIA, Cryptotanshinone etc.2010 editions " pharmacopeia " specifies, in the red sage root, content of danshinolic acid B is not less than 3.0%, and tanshinone IIA content is not less than 0.2%.
The red sage formulation of current commercial type mainly contains Radix Salviae Miltiorrhizae Tabellae, FUFANG DANSHEN DIWAN, sodium tashinone II A sulfonate injection, and sodium tashinone II A sulfonate injection clear curative effect is stable and controllable for quality, is usually used in the treatment of coronary heart diseases and angina pectoris, myocardial infarction.
China's red sage root aboundresources, cheap, added value of product is lower, and from red rooted salvia, separation and purification tanshinone IIA is significant to its exploitation.
Chinese patent (CN 103665094A) discloses and is a kind ofly separated the method preparing tanshinone IIA with macroporous resin with multi-stage counter current extraction, above-mentioned patent exist a large amount of with an organic solvent, the technical problems such as schedule of operation is loaded down with trivial details.
Summary of the invention
Because existing tanshinone IIA separation and purification exists certain yield and the lower problem of purity.The present invention adopts alcohol reflux in conjunction with the preparation method that macroporous resin is separated and recrystallization is further purified, not only yield is high for the Tanshinone II A product obtained, and purity is also very high, simultaneously technique simple possible, environmental pollution is little, has certain using value.
The present invention is based upon on a large amount of experimental data bases, constantly experiment condition is optimized, after finding that the red sage root is extracted by the ethanolic soln of suitable concentration, after extracting solution is evaporated near doing, dissolve with ethanol obtains tanshinol extract, is separated with DM130 macroporous resin, wherein absorb-elute condition is optimized through a large amount of, collect elutriant, concentrating under reduced pressure, vacuum-drying obtains Tanshinone II A crude product, after crude product recrystallization, gained tanshinone IIA yield is greater than 60%, and purity is greater than 89%.
The method extracting tanshinone IIA from the red sage root that the present invention relates to preferably comprises the following steps: described ethanol solution concentration is 70%-90% volume fraction, and preferably more than 70%.Described each ethanolic soln consumption and red rooted salvia are than being 8-12L/Kg, and that better is 10L/Kg.
Described extraction time 1-3 hour, better is extraction twice, each 1 hour.
Described macroporous resin model is DM130, and particle diameter is 0.3-1.25mm, and aperture is 90-100, and preferably particle diameter is 90, and preferably aperture is 0.3mm.
Described tanshinol extract is prepared with dissolve with ethanol by after extracting solution concentrating under reduced pressure.Wherein concentrating under reduced pressure vacuum tightness is 0.07-0.1MPa, preferably controls at 0.09MPa.Concentrating under reduced pressure temperature is 50-60 DEG C, and preferably temperature is 60 DEG C.
The sample solution of described column chromatography for separation is tanshinol extract, and be concentrated into the dissolve with ethanol solution of nearly dry rear 65%-75% volume fraction by extracting solution, better alcohol concn is 68%-73%.
In the present invention, described macroporous resin is separated into the preparation method of this area routine, preferably step is as follows: after the tanshinol extract upper prop after the dissolve with ethanol solution by 68%-73% volume fraction, the wash-out of impurity is first carried out with water, 60%-75% volume fraction ethanolic soln, use the ethanolic soln wash-out of 88%-98% volume fraction again, collect the elutriant that tanshinone IIA purity is greater than 65%.
Wherein, the consumption of the ethanolic soln of described water and 60%-75% volume fraction is 3-5 column volume, preferably 4 column volumes.The ethanolic soln consumption of described 88%-98% volume fraction is 2-4 column volume, preferably 3 column volumes.
Wherein, the consumption of described column chromatography resin is 1:1-1:10 according to red rooted salvia amount ratio, is preferably 1:1-1:5.Resin blade diameter length ratio is 1:3-1:6, is preferably 1:5.
In the present invention, after macroporous resin column chromatography has been separated, also comprise purification process-recrystallization that this area is conventional, improve the purity of tanshinone IIA crystal further.
Wherein, described recrystallization comprises the following steps: the elutriant collected by column chromatography procedure carries out concentrating under reduced pressure, vacuum-drying obtains Tanshinone II A crude product, crude product chloroform dissolves, chloroform add-on is just can dissolve crude product, in gained chloroformic solution, add distilled water to solution occurs muddy, and turbid solution lucifuge under 2-4 DEG C of condition is left standstill more than 24 hours, and suction filtration obtains tanshinone IIA crystal.
In the present invention, the tanshinone IIA crystal purity through re-crystallization step is greater than 89%, and yield is greater than 60%(HPLC and detects).
In the present invention, meeting under the basic general knowledge condition in this area, arbitrarily to the Parameter Conditions combination in invention, can preferred embodiments obtained.
Novelty advantage of the present invention is:
(1) by preparation method of the present invention, not only tanshinone IIA yield is high, and can reach very high purity.
(2) preparation method of the present invention, technique simple possible, pollutes little, has and necessarily amplify productive value.
Embodiment
Further illustrate the present invention with example below, but the present invention does not limit by illustrative example technical scheme.
Embodiment one:
Get 100g red rooted salvia, with 70% alcohol heat reflux twice, add 1000ml70% ethanol at every turn, extraction time is respectively 1 hour, 0.5 hour.Extracting solution is evaporated to nearly dry dissolve with ethanol at 60 DEG C and obtains tanshinol extract.
The DM130 macroporous resin getting 60g activation fills in the chromatography column that internal diameter is 2.5cm, and resin layer height is 14cm.Get tanshinol extract loading, then use 4BV water, 70% volume fraction ethanol wash-out impurity successively respectively, then use 2BV95% volume fraction ethanol elution tanshinone IIA, collect elutriant.Detected by HPLC, obtaining tanshinone IIA purity in elutriant is 79.5%, yield 75.4%.
Elutriant is evaporated to dry, dissolves with the chloroform of 1 times of sample volume, in chloroformic solution, slowly add distilled water, to muddiness appears in solution.Turbid solution lucifuge in 2 DEG C of refrigerators leaves standstill crystallization in 24 hours, and suction filtration obtains tanshinone IIA crystal.HPLC detects tanshinone IIA purity 89.2%, and yield is 60.4%.
Embodiment two:
Get 100g red rooted salvia, with 80% volume fraction alcohol reflux twice, first time adds 1200ml75% volume fraction extraction using alcohol 1 hour, and second time adds 1000ml75% volume fraction extraction using alcohol 1 hour, extracting solution is evaporated to dry at 60 DEG C, adds dissolve with ethanol and obtains tanshinol extract.
Get the DM130 resin that 78g is activated, fill in chromatography column that internal diameter is 3cm, packed height is 13cm.Get tanshinol extract loading, then use 5BV distilled water, 75% volume fraction ethanol wash-out impurity successively respectively.Use 3BV98% volume fraction ethanol elution tanshinone IIA again, collect elutriant.Detect through HPLC, in elutriant, tanshinone IIA purity is 73.9%, and yield is 78.8%.
Elutriant is evaporated to dry, dissolves with the chloroform of 2 times of sample volumes, in chloroformic solution, slowly add distilled water, to muddiness appears in solution.Turbid solution is the crystallization of lucifuge hold over night in 2 DEG C of refrigerators, and suction filtration obtains tanshinone IIA crystal.HPLC detects tanshinone IIA purity 91.8%, and yield is 64.4%.
The above is the preferred embodiment of the present invention, it is pointed out that the those of ordinary skill for understanding this area general knowledge, and under the technology of the present invention inspires, suitable parameter modification is also regarded as protection scope of the present invention.
Claims (10)
1. the preparation method of a tanshinone IIA, it comprises following steps: the alcohol heat reflux of red sage root 70%-90% is extracted 1-3 hour, filtrate reduced in volume obtains tanshinol extract to nearly dry rear dissolve with ethanol, column chromatography for separation is carried out with macroporous resin, collect elutriant, concentrating under reduced pressure, vacuum-drying obtain Tanshinone II A crude product, crude product recrystallization.
2. preparation method as claimed in claim 1, it is characterized in that: described macroporous resin model is DM130, its particle diameter is 0.3-1.25mm, and aperture is 90-100, and resin matrix is crosslinked polystyrene.
3. preparation method as claimed in claim 1, it is characterized in that: described concentrating under reduced pressure vacuum tightness is 0.07-0.1MPa, concentrating under reduced pressure temperature is 50-60 DEG C.
4. preparation method as claimed in claim 1, is characterized in that: described tanshinol extract is obtained by following method: dissolve after Radix Salviae Miltiorrhizae extract being evaporated near doing.
5. preparation method as claimed in claim 4, it is characterized in that: described Radix Salviae Miltiorrhizae extract is obtained by following method: extracted by red rooted salvia alcohol heat reflux, wherein, described ethanol solution concentration is 70%-90%; Described ethanolic soln is 8-12L/Kg with the volume mass ratio of red rooted salvia; Described extraction time is 1-3h; Described extraction time is 1-2 time.
6. the preparation method as described in any one of claim 1 and 2, it is characterized in that: the step that described macroporous resin column chromatography is separated is as follows: after tanshinol extract loading, first use the ethanolic soln wash-out impurity of distilled water and 60%-75% volume fraction, wash-out is carried out again with the ethanolic soln of 88%-98% volume fraction, collect the elutriant that tanshinone IIA purity is greater than 65%.
7. preparation method as claimed in claim 6, it is characterized in that: the consumption of the ethanolic soln of described distilled water and 60%-75% volume fraction is 3-5 column volume, the consumption of the ethanolic soln of 88%-98% volume fraction is 2-4 column volume.
8. preparation method as claimed in claim 1, is characterized in that: before tanshinol extract macroporous resin column chromatography is separated, and Radix Salviae Miltiorrhizae extract is concentrated into the dissolve with ethanol solution of nearly dry 65%-75% volume fraction, upper macroporous resin column is separated.
9. the preparation method as described in claim 1, it is characterized in that: after macroporous resin column chromatography is separated, further comprising the steps of: the Tanshinone II A crude product obtained by column chromatography carries out common solid matter purification step-recrystallization, obtain the tanshinone IIA crystallization of purity more than 89%,, wherein, recrystallization process comprises following steps:
A. the elutriant collected by column chromatography procedure carries out concentrating under reduced pressure, and enriched material chloroform dissolves;
B. in gained chloroformic solution, add distilled water to solution occurs muddy, turbid solution lucifuge under 2-4 DEG C of condition is left standstill more than 24 hours, obtains tanshinone IIA crystal.
10. preparation method as claimed in claim 9, is characterized in that: the turbid solution static conditions described in b step is lucifuge 2 DEG C.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410808695.6A CN104530181A (en) | 2014-12-24 | 2014-12-24 | Method for preparing tanshinone II A |
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| CN201410808695.6A CN104530181A (en) | 2014-12-24 | 2014-12-24 | Method for preparing tanshinone II A |
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| CN104530181A true CN104530181A (en) | 2015-04-22 |
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| CN201410808695.6A Pending CN104530181A (en) | 2014-12-24 | 2014-12-24 | Method for preparing tanshinone II A |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110156866A (en) * | 2019-05-16 | 2019-08-23 | 三门峡职业技术学院 | A kind of method of molecularly distilled purification tanshinone IIA |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103665094A (en) * | 2013-10-22 | 2014-03-26 | 南京慧博生物科技有限公司 | Preparation method for extracting and purifying tanshinone monomeric compounds from red sage root |
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2014
- 2014-12-24 CN CN201410808695.6A patent/CN104530181A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103665094A (en) * | 2013-10-22 | 2014-03-26 | 南京慧博生物科技有限公司 | Preparation method for extracting and purifying tanshinone monomeric compounds from red sage root |
Non-Patent Citations (1)
| Title |
|---|
| 陈少兵: "丹参有效部位的制备工艺与稳定性研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》, no. 05, 15 May 2008 (2008-05-15), pages 18 - 20 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110156866A (en) * | 2019-05-16 | 2019-08-23 | 三门峡职业技术学院 | A kind of method of molecularly distilled purification tanshinone IIA |
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| PB01 | Publication | ||
| C53 | Correction of patent of invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Fu Jing Inventor after: Zhang Zhiqiang Inventor after: Liu Wu Inventor after: Zhou Yongkang Inventor before: Liu Wu Inventor before: Zhou Yongkang Inventor before: Sun Na |
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| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: LIU WU ZHOU YONGKANG SUN NA TO: FU JING ZHANG ZHIQIANG LIU WU ZHOU YONGKANG |
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| EXSB | Decision made by sipo to initiate substantive examination | ||
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Application publication date: 20150422 |