CN101353306A - Refining method of salvianolic acid A - Google Patents
Refining method of salvianolic acid A Download PDFInfo
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- CN101353306A CN101353306A CNA2008101207846A CN200810120784A CN101353306A CN 101353306 A CN101353306 A CN 101353306A CN A2008101207846 A CNA2008101207846 A CN A2008101207846A CN 200810120784 A CN200810120784 A CN 200810120784A CN 101353306 A CN101353306 A CN 101353306A
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Abstract
The invention provides a purification method of a salvianolic acid A. A salvia miltiorrhiza water extract is extracted by an organic solvent extraction method to obtain a crude extract of the salvianolic acid A, the crude extract is extracted by acid water to remove impurities, and the crude extract without the impurity is condensed and dried by an organic phase to obtain the high-purity salvianolic acid A. The purification method of the invention has more than 95% purification recovery rate and more than 90% purity of the salvianolic acid A (calculated based on medicinal material weight and the yield is more than 0.3%). The most important point is that the main purification process of the method is of a liquid-liquid extraction, which simplifies the process and the required equipment, and the method is suitable for large-scale industrial production. The purification method has the advantages of reasonable design, high fine purification recovery rate, good purity, stable performance, simple preparation process and low production cost.
Description
Technical field
The invention belongs to the purification of tcm method, relate generally to a kind of process for purification of Chinese medicine salvianolic acid A.
Background technology
The red sage root is one of the most frequently used Chinese medicine medicinal material.Be used for the treatment of cardiovascular and cerebrovascular diseases such as stenocardia, hypertension, coronary heart disease and apoplexy.The Chinese medicine preparation that is used as medicine with salvia piece or red sage root crude extract has a lot, as FUFANG DANSHEN PIAN, FUFANG DANSHEN DIWAN, Radix Salviae Miltiorrhizae Injection, XIANGDAN ZHUSHEYE etc., the preparation that also has utilization to separate from the red sage root in addition to obtain pure compound or its esters to make is as Sodium Danshensu injection liquid, salvianolic acid B injection etc.
In recent years, along with going deep into of pharmacological research, the multiple pharmacologically active of salvianolic acid A is found.Has anti-tumor activity as discovery salvianolic acid As such as Zhen Yongsu; Discovery salvianolic acid As such as Du Guanhua have significant protective effect to the isolated rat myocardial ischemia-reperfusion injury, the brain injury that the mouse brain ischemia-reperfusion is caused has provide protection, and the mouse memory acquired disturbance that Daturamine or winter tropine are caused improves significantly etc.; Inscription on pottery discovery salvianolic acid As such as (Tao Wen) has provide protection to the rats'liver damage that tetracol phenixin causes.Li Zhigangs etc. have also been developed the red sage root salvianolic acid A tablet and the injection of treatment cardiovascular disorder.
The relevant patent of the preparation salvianolic acid A of having applied for more (seeing Table 1) all comprise the separation method (chromatographic separation and solvent extraction, protein adsorption and solvent extraction) of two or more different principle, thereby processing step is more, needs multiple plant and instrument.
The comparison of table 1. patent applied for.
| Patent publication No. | Principle and step | Yield | Purity |
| CN1830947A | Water or alcohol extracting, concentrated back high-temperature high-voltage reaction, column chromatography, adjusting pH value, organic solvent extraction | More than 0.35% | More than 80% |
| CN1887849 | Water or alcohol extracting, column chromatography are regulated pH value, organic solvent extraction | More than 0.3% | More than 90% |
| CN101041620 | Water or alcohol extracting, column chromatography are regulated pH value, organic solvent extraction | - | 90％ |
| CN101230003 | Water or alcohol extracting, acid adjustment, thermal conversion, resin column chromatography | 1％-2％ | - |
| CN101130498 | Water or alcohol extracting, protein adsorption, parsing, organic solvent extraction | 0.3％ | More than 90% |
Because salvianolic acid A content in medicinal material is very low, processing step is many more, and the process loss is big more.In addition, column chromatography uses in the big production of industry certain limitation, can not satisfy the needs of industrial production salvianolic acid A preparation well.
Summary of the invention
The present invention is directed to the deficiency that above-mentioned prior art exists, a kind of process for purification of salvianolic acid A is provided, be achieved through the following technical solutions: the organic phase that adopt organic solvent extractionprocess extraction red sage root water extract to obtain salvianolic acid A crude extract (organic phase), to adopt the sour water extraction process to remove impurity, contains refining salvianolic acid A through concentrate, dry after acquisition pale yellow powder, i.e. high-purity danshinolic acid A.Be specifically related to following steps:
1, abstraction purification
Adopt the salvianolic acid A in the organic solvent extraction enrichment red sage root water extract, through the sour water removal impurity of repeatedly stripping, obtain highly purified salvianolic acid A again.
(1) gets red sage root water extract to be extracted, add organic solvent and extract, separate the organic solvent layer that contains salvianolic acid A.
(2) get the organic solvent layer that contains salvianolic acid A and directly or after concentrating repeatedly extract removal impurity, separate the organic solvent layer that contains refining salvianolic acid A with sour water.
Wherein the extracting mode such as adopt that normal reflux, temperature are soaked of the red sage root water extract in the step (1) extracts from red rooted salvia and obtains.Used organic solvent is acetate esters solvents such as ethyl acetate, propyl acetate, butylacetate, and extraction times is 2～10 times.The organic solvent amount that is used to extract is 1～5 times of red sage root water liquid-extracting amount.
In the step (2) to regulate the acid of sour water pH value be mineral acid, sour water pH value scope is 1～5, extraction times is 3～10 times.
2, concentrate drying
Concentrate and adopt concentrating under reduced pressure or normal pressure to concentrate, dry employing vacuum-drying or lyophilize.
Salvianolic acid A purification process of the present invention, utilize the polarity character littler of salvianolic acid A, rancinamycin IV than the polarity of Salvianic acidA, salvianolic acid B, adopt organic solvent extracting and enriching under pH4～6 conditions mainly to be contained the salvianolic acid A crude extract of salvianolic acid A and rancinamycin IV, utilize under salvianolic acid A and the rancinamycin IV acidic conditions the different of in water solubleness again, through the sour water removal rancinamycin IV of repeatedly stripping, obtain highly purified salvianolic acid A, thereby reach the purpose of separation and purification salvianolic acid A.This method purifying rate of recovery reaches more than 95%%, the purity of salvianolic acid A reaches (in medicinal material weight, yield is more than 0.3%) more than 90%, and most importantly main means of purification only is liquid-liquid extraction in this technology, thereby make technology and required equipment more simple, be fit to the big production of industry.This method makes with extra care that rate of recovery height, purity are good, stable performance, technology is simple, production cost is low process for purification
Description of drawings
Fig. 1 salvianolic acid A crude extract HPLC color atlas.
Fig. 2 salvianolic acid A purity test color atlas.
Specific embodiments
Embodiment 1: the extracting and purifying method of salvianolic acid A the steps include:
1. get salvia piece 100g, add 1L water, refluxing extraction 2 hours is filtered, filter residue adds 0.8L water again, and refluxing extraction 1.5 hours is filtered, and merges filtrate twice, 70 ℃ are evaporated to about 50mL, use equal volume of ethyl acetate 3 times, merge organic phase, are concentrated into 1/3 volume;
2. to regulate water pH value be 1 to hydrochloric acid, with spissated organic extractant phase in the step 15 times, casts out water, and the concentrating under reduced pressure organic phase is to the medicinal extract shape, and lyophilize gets pale yellow powder, is salvianolic acid A.Its purity is 92%, and the rate of recovery is 97%.
The result is referring to Fig. 1 and Fig. 2, and peak A is a salvianolic acid A among the figure.
Embodiment 2: removing extraction solvent is propyl acetate, and the propyl acetate amount of adding is that all the other steps are identical with embodiment 1 outside 3 times of amounts of red sage root water extract.Its purity is 93%, and the rate of recovery is 95%.
Embodiment 3: removing extraction solvent is butylacetate, and extraction times is outside 5 times, and all the other steps are identical with embodiment 1.Its purity is 93%, and the rate of recovery is 95%.
Embodiment 4: except that used aqueous acid pH value in the step 2 is 2, (50 ℃, vacuum tightness-0.09MPa), all the other steps are identical with embodiment 1 in dry employing vacuum-drying.Its purity is 95%, and the rate of recovery is 95%.
Embodiment 5: except that used aqueous acid pH value in the step 2 is 3, all the other steps are identical with embodiment 1.Its purity is 91%, and the rate of recovery is 96%.
Embodiment 6: be 7 times except that sour water extraction times in the step 2, all the other steps are identical with embodiment 1.Its purity is 94%, and the rate of recovery is 95%.
Embodiment 7: except that sour water extraction times in the step 2 is 10 times, all the other steps are identical with embodiment 1.Its purity is 96%, and the rate of recovery is 95%.
Embodiment 8: except that used mineral acid in the step 2 is the sulfuric acid, all the other steps are identical with embodiment 1.Its purity is 92%, and the rate of recovery is 95%.
Embodiment 9: except that used mineral acid in the step 2 is a phosphoric acid, sour water pH value is outside 4, and all the other steps are identical with embodiment 1.Its purity is 90%, and the rate of recovery is 95%.
Claims (7)
1. the process for purification of a salvianolic acid A, it is characterized in that realizing by following steps: the extracting mode that (1) adopts normal reflux mode or temperature to soak extracts red sage root water extract from red rooted salvia, with the salvianolic acid A in the organic solvent extractionprocess extraction red sage root water extract, separate and contain the organic solvent layer of salvianolic acid A as organic phase, adopt the sour water extraction process to remove impurity, acquisition contains the organic solvent phase of salvianolic acid A, the pH value of used sour water is 1～5, (2) organic phase that will contain salvianolic acid A obtains pale yellow powder after concentrating under reduced pressure, vacuum-drying, i.e. high-purity danshinolic acid A.
2. the process for purification of a kind of salvianolic acid A according to claim 1, it is characterized in that: the pH value of the described red sage root water of step (1) extract is 4～6.
3. the process for purification of a kind of salvianolic acid A according to claim 1, it is characterized in that: the described organic solvent extraction number of times of step (1) is 2～10 times, the organic solvent amount that is used to extract is 1～5 times of red sage root water liquid-extracting amount, and used organic solvent is the acetate esters solvent.
4. the process for purification of a kind of salvianolic acid A according to claim 3, it is characterized in that: extracting used organic solvent is ethyl acetate, propyl acetate or butylacetate.
5. the process for purification of a kind of salvianolic acid A according to claim 1 is characterized in that: regulating the used acid of sour water pH in the step (1) is mineral acid, and extraction times is 3～10 times.
6. the process for purification of a kind of salvianolic acid A according to claim 1 is characterized in that: the described concentrated employing normal pressure of step (2) concentrates.
7. the process for purification of a kind of salvianolic acid A according to claim 1 is characterized in that: the described dry lyophilize of adopting of step (2).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101207846A CN101353306B (en) | 2008-09-05 | 2008-09-05 | Refining method of salvianolic acid A |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2008101207846A CN101353306B (en) | 2008-09-05 | 2008-09-05 | Refining method of salvianolic acid A |
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| Publication Number | Publication Date |
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| CN101353306A true CN101353306A (en) | 2009-01-28 |
| CN101353306B CN101353306B (en) | 2011-05-18 |
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| CN2008101207846A Expired - Fee Related CN101353306B (en) | 2008-09-05 | 2008-09-05 | Refining method of salvianolic acid A |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102993015A (en) * | 2012-11-20 | 2013-03-27 | 楚健 | Method for purifying salvianolic acid A |
| CN103044251A (en) * | 2012-11-20 | 2013-04-17 | 吕武清 | Method for preparing salvianolic acid A |
| CN107032996A (en) * | 2017-05-12 | 2017-08-11 | 浙江大学 | It is a kind of while the method for refined salviandic acid A and protocatechualdehyde |
| CN109748793A (en) * | 2018-12-29 | 2019-05-14 | 正大青春宝药业有限公司 | A method of different salviandic acid A 1 and different salviandic acid A 2 in removal salviandic acid A sodium |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1887849A (en) * | 2006-07-13 | 2007-01-03 | 正大青春宝药业有限公司 | Salvianolic acid A preparing process |
| CN101130498B (en) * | 2007-08-24 | 2012-08-29 | 浙江大学 | Method for extracting and purifying salvianolic acid A |
-
2008
- 2008-09-05 CN CN2008101207846A patent/CN101353306B/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102993015A (en) * | 2012-11-20 | 2013-03-27 | 楚健 | Method for purifying salvianolic acid A |
| CN103044251A (en) * | 2012-11-20 | 2013-04-17 | 吕武清 | Method for preparing salvianolic acid A |
| CN103044251B (en) * | 2012-11-20 | 2015-01-07 | 江西青峰药业有限公司 | Method for preparing salvianolic acid A |
| CN102993015B (en) * | 2012-11-20 | 2015-04-08 | 江西青峰药业有限公司 | Method for purifying salvianolic acid A |
| CN107032996A (en) * | 2017-05-12 | 2017-08-11 | 浙江大学 | It is a kind of while the method for refined salviandic acid A and protocatechualdehyde |
| CN107032996B (en) * | 2017-05-12 | 2019-07-09 | 浙江大学 | Method that is a kind of while refining salviandic acid A and protocatechualdehyde |
| CN109748793A (en) * | 2018-12-29 | 2019-05-14 | 正大青春宝药业有限公司 | A method of different salviandic acid A 1 and different salviandic acid A 2 in removal salviandic acid A sodium |
| CN109748793B (en) * | 2018-12-29 | 2021-07-09 | 正大青春宝药业有限公司 | Method for removing isosalvianolic acid A1 and isosalvianolic acid A2 from sodium salvianolic acid A |
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| CN101353306B (en) | 2011-05-18 |
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