CN106431915B - A kind of preparation method of salviandic acid A - Google Patents
A kind of preparation method of salviandic acid A Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
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Abstract
The invention discloses a kind of preparation methods of salviandic acid A, and steps are as follows: (1) by tanshin polyphenolic acid B with the pH NaOH for being 3.5-4.5 or NaHCO3Water is configured to the solution of 35-45mg/mL, it is placed in subcritical water reaction kettle, after heating furnace reaches 170 DEG C -190 DEG C and stablizes, reaction kettle is put into heating furnace, reaction kettle is taken out after 50min-70min and is put into cooling in ice-water bath or cold water punching, liquid is taken out, is freeze-dried, obtains rich in salviandic acid A crude product；(3) isolate and purify salviandic acid A using high speed adverse current chromatogram: solvent system is petroleum ether: ethyl acetate: n-butanol: water=2:3:1:9, upper addition 10mM trifluoroacetic acid is stationary phase, it is mobile phase that lower phase, which is 10mM ammonium hydroxide, high-speed counter-current chromatograph column volume is 200-400mL, applied sample amount 1.0-1.2g, revolving speed 600-1000rpm, flow velocity 1-4mL/min, Detection wavelength 280nm.The method of the present invention is at low cost, easy to operate, high-efficient, can relatively high-volume convert danshinolic acid crude extract, the salviandic acid A monomeric compound that purity is greater than 98% is prepared in separation.
Description
Technical field
The invention belongs to the efficient preparation technical fields of effective component of chinese medicine, and in particular to a kind of preparation side of salviandic acid A
Method.
Background technique
Radix Salviae Miltiorrhizae is the dry root and rhizome of Lamiaceae plant Radix Salviae Miltiorrhizae Salvia miltiorrhizaBge., and there is promoting blood circulation to dispel
The stasis of blood, inducing meastruation to relieve menalgia, relieving restlessness and restlessness, cool blood to disappear carbuncle and other effects.For chest impediment and cardialgia, stomach duct and abdomen hypochondriac pain , lumps in the chest and abdomen, hot numbness pain,
Dysphoria and insomnia, irregular menstruation, dysmenorrhea menostasis, the diseases such as sore swell and ache curative.In recent years, research discovery Radix Salviae Miltiorrhizae has expansion coronary artery, resist
Platelet aggregation improves blood circulation, prevents thrombosis and atherosclerotic plaque from being formed, and promotes pathological change recovery etc.
Effect, and it is widely used in the ischemic diseases such as quality cardiovascular and cerebrovascular.Radix Salviae Miltiorrhizae has become China's dosage maximum, sale at present
The most Chinese medicine of volume highest, preparation manufacturer, the red sage formulation of clinical use specifically include that compound danshen dripping pills, compound are red
Join injection, Fufang Danshen Pian, salvia root polyphenol acid salt injection etc..Chemical component is broadly divided into two major classes in Radix Salviae Miltiorrhizae: water-soluble
Ingredient, i.e. phenolic acid compound；Liposoluble constituent, i.e. diterpene quinone.The end of the sixties, researcher was to Salvia miltiorrhiza Bge water so far
Soluble components have made intensive studies, it was demonstrated that its principle active component is phenolic acid compound.The salvia-soluble reported earliest
Ingredient is protocatechualdehyde, reports that danshensu is the basic structure of various salvianolic acid compounds later.It is isolated later a series of
Pressure differential self, such as salviandic acid A~K, Rosmarinic acid, alkannic acid, they all have anti peroxidation of lipid and remove certainly
It is acted on by base, wherein salviandic acid A (Salvianolic acid A) activity is most strong.
The existing preparation method about salviandic acid A has direct the preparation method and indirect reformer method.Direct the preparation method is divided into two kinds,
One kind is direct synthesis technique (such as patent CN201410216134.7), passes through demethylating reaction system using salviandic acid A synthesis precursor
Standby salviandic acid A, then purified through preparative HPLC, purity can be improved to 97%；One kind is direct method of isolation, (such as patent
CN201010541651.3), using red rooted salvia as raw material, the methods of extracted, rough segmentation, decoloration, purifying obtain high-purity pellet phenol
Sour A monomer.For indirect reformer method (such as patent CN201310487751.6) for Radix Salviae Miltiorrhizae or tanshin polyphenolic acid B is heated, tune soda acid is anti-
Several hours are answered, convert salviandic acid A for tanshin polyphenolic acid B, then obtain high-purity danshinolic acid A through preparative separation.Direct the preparation method and
The disadvantages of that all there is preparation efficiencies is low for indirect reformer method, and conversion rate is slow, while obtaining the component rich in salviandic acid A and need to combine
Polyamide chromatography, macroreticular resin, silica gel column chromatography and preparative liquid chromatography are separated, time-consuming and laborious, pollution environment, sample
Purity is low, and column chromatography has an irreversibility suction-operated to sample repeatedly, isolated salviandic acid A monomer preparation efficiency is low,
Higher cost, it is difficult to develop into the big isolation technics of preparation amount.
Heat water to boiling point or more, critical point hereinafter, simultaneously control system pressure makes water remain liquid, this state
Water is referred to as subcritical water.Under usual conditions, water is polar compound, under 505kPa pressure, increases (50~300 with temperature
DEG C), dielectric constant is decreased to 1 by 70, that is to say, that its property fades to nonpolarity by highly polar, can by solute by polarity by
It is high to Low to extract.It, can be with extracting apolar compound under the conditions of temperature and pressure is all higher, the reduction of the polarity of water；
Under the conditions of temperature and pressure is all lower, the polarity of water is improved, and can extract polar compound.Due to be without using acid, alkali and
Processing technique of the water of catalyst under high thermal high, therefore the extracting method of subcritical water is referred to as " green processing
Method ".In addition, extracting can complete within short time of the several seconds to several minutes, have the advantages that continuous processing can be carried out.Together
When subcritical water there is the different property of " strong dissolved organic matter is in water " and " strong decomposing force " equally light water.Benefit
With this property, subcritical water is utilized to extract useful component (including extracting the decomposition product generated with decomposition reaction).It is sub-
Critical technology for hydrolyzing is the hot spot of natural product extraction and Study on Transformation field in recent years.It is used for natural product extraction conversion tool
There are simple fast reaction rate, solvent-free pollution, early period and post-processing step, high income, that low energy consumption etc. is unique.
High speed adverse current chromatogram (High-speed Counter-current Chromatography, HSCCC) is nearly 30 years
A kind of efficient, the quick liquid liquid partition chromatography isolation technics for being continuously not necessarily to any solid support to grow up, it keeps away
Solid state adhesion body or carrier bring sample are exempted from easily by various problems such as dead absorption, loss and denaturation.PH- zone purification adverse current
Chromatography (pH-Zone-Refining Countercurrent Chromatography) is then in common high speed adverse current chromatogram
On the basis of instrument, sample sets are made using the means of chemistry by the allotment of the composition to solvent system used in separation sample
The chromatographic separation process divided adds the feature assembled by pH zone, meanwhile, so that the elution process of component is shown as similar displacement
The elution process of (replacement) chromatography (Displacement Chromatography), therefore, its chromatogram are no longer Gausses point
The chromatographic peak profile series of cloth, and become the rectangle region band series precipitous by the boundary of the big minispread of pH value, as a result, can handle
The separation preparation amount of the adverse current chromatogram instrument of same volume improves several times or even ten times.
Summary of the invention
The object of the present invention is to provide a kind of preparation methods of salviandic acid A.
A kind of preparation method of salviandic acid A, steps are as follows:
(1) be with pH by tanshin polyphenolic acid B (preferably 4.0) 3.5-4.5 NaOH or NaHCO3(NaHCO3Advantage: alkalinity is weaker,
Reacting milder) water is configured to the solution of 35-45mg/mL (preferably: 40mg/mL), it is placed in subcritical water stainless steel cauldron,
After heating furnace reaches 170 DEG C -190 DEG C (preferably: 180 DEG C) and stablizes, reaction kettle is put into heating furnace, 50min-70min is (preferably
60min) afterwards rapidly take out reaction kettle and be put into ice-water bath or cold water punching (advantage: fast cooling, prevent during cooling after
Continuous reaction) in it is cooling, liquid is taken out, is freeze-dried, obtains rich in salviandic acid A crude product；
(2) isolate and purify salviandic acid A using high speed adverse current chromatogram: solvent system is petroleum ether: ethyl acetate: n-butanol:
Water=2:3:1:9, upper addition 10mM trifluoroacetic acid are stationary phase, and lower phase is that 10mM ammonium hydroxide is mobile phase, high-speed counter-current chromatograph
Column volume be 200-400 (preferably 300) mL, applied sample amount 1.0-1.2g (preferably 1.2g), revolving speed 600-1000rpm (preferably:
800rpm), upper phase is stationary phase, and lower phase is mobile phase, flow velocity 1-4mL/min (preferably: 2.0mL/min), stationary phase retention rate
57%, Detection wavelength 280nm.
One kind having expansion coronary artery, platelet aggregation-against, improves blood circulation, prevents thrombosis, atherosclerosis
Patch forms, promotes the preparation method of the drug of pathological change recovery, has the step of above-mentioned salviandic acid A preparation method.
Beneficial effects of the present invention:
1, preparation method of the invention is converted using supercritical water and converts salviandic acid A crude product for tanshin polyphenolic acid B, is finally passed through
High speed adverse current chromatogram isolates and purifies salviandic acid A, and cost is lower than the prior art, easy to operate, high-efficient, can relatively high-volume will be red
Phenolic acid crude extract is converted, and the salviandic acid A monomeric compound that purity is greater than 98% is prepared in separation.
2, there is the method using extracting fat soluble component in Chinese medicine red sage root by subcritical water etc. at present, but these methods are all
Subcritical water is utilized under the conditions of temperature and pressure is all higher, the reduction of the polarity of water, the effect of extracting apolar compound,
And the present invention makes full use of subcritical water high to Tanshin Water-soluble Ingredient solubility, cannot be only used for the extraction of Related Component,
Simultaneously also using high temperature and pressure the characteristics of, convert the higher salviandic acid A of bioactivity for tanshin polyphenolic acid B.
3, the NaHCO for being 4.0 with pH by tanshin polyphenolic acid B3Water is configured to the solution purpose of 40mg/mL: the experiment proved that, in pellet
Acid or alkali are added in phenolic acid B, can accelerate the conversion rate of tanshin polyphenolic acid B, but only most have when pH is 4.0 or so
It is converted conducive to tanshin polyphenolic acid B to the direction of salviandic acid A, makes the yield highest of salviandic acid A.Advantage: the production of salviandic acid A both can be improved
Amount, and the conversion rate of tanshin polyphenolic acid B can be accelerated.
4, after heating furnace reaches 180 DEG C and stablizes, reaction kettle is put into heating furnace, the purpose after 60min: heating furnace reaction
Before reach stable state, be conducive to carry out control on time and temperature to entire reaction, be improved the reproducibility of reaction.
Advantage: energy-efficient, conversion is completely.
Detailed description of the invention
Fig. 1 is the process flow chart of embodiment 1；
Fig. 2 is the zone adverse current chromatogram figure that embodiment 1 is rich in the separation of salviandic acid A crude product, a: danshensu；B: salvianolic acid D；C:
Salviandic acid A；D: protocatechualdehyde；
Fig. 3 is the high-efficient liquid phase chromatogram of 1 tanshin polyphenolic acid B sample of embodiment；
Fig. 4 is the high-efficient liquid phase chromatogram that embodiment 1 is rich in salviandic acid A crude product；
Fig. 5 is the high-efficient liquid phase chromatogram of 1 danshensu monomer of embodiment；
Fig. 6 is the high-efficient liquid phase chromatogram of 1 salvianolic acid D monomer of embodiment；
Fig. 7 is the high-efficient liquid phase chromatogram of 1 salviandic acid A monomer of embodiment；
Fig. 8 is the high-efficient liquid phase chromatogram of 1 protocatechualdehyde monomer of embodiment；
Fig. 9 is the zone adverse current chromatogram figure of comparative example 1；
Figure 10 is the zone adverse current chromatogram figure of comparative example 2.
Specific embodiment
The invention will be further described with embodiment with reference to the accompanying drawing.
Embodiment 1
As shown in Fig. 1 salviandic acid A monomer preparation flow figure.
The NaHCO for being 4.0 with pH by tanshin polyphenolic acid B (Fig. 3)3Water is configured to the tanshin polyphenolic acid B solution of 40mg/mL, takes on 40mL
It states solution to be placed in 50mL subcritical water stainless steel cauldron, after heating furnace reaches 180 DEG C and stablizes, reaction kettle is put into heating
Furnace starts timing.Reactor is taken out after 60min rapidly and is put into cooling in ice-water bath, liquid is taken out, is freeze-dried, obtains rich
Crude product containing salviandic acid A (Fig. 4).
2. isolating and purifying salviandic acid A using high speed adverse current chromatogram
Solvent system is petroleum ether: ethyl acetate: n-butanol: water=2:3:1:9, and upper addition 10Mm trifluoroacetic acid is to fix
Phase, it is mobile phase that lower phase, which is 10mM ammonium hydroxide, and high-speed counter-current chromatograph column volume is 300mL, applied sample amount 1.2g, revolving speed 800rpm,
Upper phase is stationary phase, and lower phase is mobile phase, flow velocity 2.0mL/min, stationary phase retention rate 57%, Detection wavelength 280nm.
Specific operating procedure is: preparing solvent system by above-mentioned solvent ratios, is placed in separatory funnel, stands after shaking up
Layering, ready to balance for a period of time afterwards separate upper and lower two-phase, and upper addition 10mM trifluoroacetic acid is stationary phase, and lower phase is 10Mm ammonium hydroxide
For mobile phase, takes 1.2g rich in salviandic acid A crude product, be dissolved in 5mL and the upper phase of 10mM trifluoroacetic acid and 5mL is added to be not added under ammonium hydroxide
It is stand-by in phase.The semi-preparative high-speed counter-current chromatograph developed using Shanghai with field company, it is by plunger pump, sampling valve, purple
Outer detector, recorder and chromatography column (spiral tube formed by polyfluortetraethylene pipe multi-lay winding, capacity 300mL)
Deng composition, sampling valve is made to be in sample introduction state first, stationary phase is filled into chromatography column with pump with certain flow rate, termination of pumping.It opens
Speed control is opened, the chromatographic chromatography column of high velocity stream is rotated forward, when turn up 800rpm, by sample dissolve note
Emitter is injected in the liquid storage tube of counter-current chromatograph sampling valve, and rotation sampling valve is to connect column state, and sample is made to enter chromatography column.
Setting flow rate of mobile phase is 2.0mL/min, starts to pump mobile phase, then receives target according to detector ultraviolet spectrogram (Fig. 2)
Ingredient obtains danshensu (38.9mg, Fig. 5), salvianolic acid D (9.5mg, Fig. 6), salviandic acid A (227.3mg, Fig. 7) and protocatechualdehyde
(32.8mg, Fig. 8), HPLC purity assay are 98% or more.
Utilize efficient liquid phase chromatographic analysis isolate, liquid-phase condition: Kromasil 100-5C18Column (4.6 × 250mm) is purple
Outer Detection wavelength 286nm, column temperature: 25 DEG C, flow velocity: 1.0mL/min, sample volume: 10 μ L, mobile phase use acetonitrile (A) and 0.2%
Aqueous formic acid (B) gradient elution, gradient condition are as follows: 0-9min, 10%-22%A；9-19min, 22%-24%A；19-
35min, 24%A；35-43min, 24%-36%A；43-48min, 36%-100%A；48-50min, 100%A.
Structural Identification: to isolated alkaloid application Agilent 5973N mass spectrograph and Varian 600MHz nuclear-magnetism
Resonance spectrometer carries out MS respectively,1The measurement of HNMR spectrum, the data obtained are as follows:
Danshensu: ESI-MS, m/z, 197 [M-H]-,395[2M-H]-,135[M-H-H2O-CO2]-.1H-NMR(DMSO-
d6, 400MHz) and δ: 2.51 (1H, dd, J=5.6,9.2Hz, H-7), 2.85 (1H, dd, J=2.4,9.2Hz, H-7), 3.90
(1H, dd, J=2.5,5.6Hz, H-8), 6.45 (1H, dd, J=1.3,5.3Hz, H-6), 6.61 (1H, d, J=5.3Hz, H-
5),6.65(1H,s,H-2).13C-NMR(DMSO-d6,100MHz)δ:49.1(C-7),72.6(C-8),115.7(C-5),
117.5(C-2),120.5(C-6),130.5(C-1),143.9(C-3),145.2(C-4),177.1(C-9).
Salvianolic acid D: ESI-MS, m/z, 417 [M-H]-,373[M-H-CO2]-,197[C9H10O5-H]-,175[M-H-CO2-
C9H10O5]-.1H-NMR(DMSO-d6, 400MHz) and δ: 2.96 (2H, m, H-7 "), 4.85 (1H, dd, J=8.1,8.5Hz, H-
8″),3.58(2H,s,Ar-CH2), 6.24 (1H, d, J=16.0Hz, H-8), 7.86 (1H, d, J=16.0, H-7), 6.47-
7.07(5H,Ar-H).13C-NMR(DMSO-d6,100MHz)δ:37.5(C-2′),49.1(C-7″),75.0(C-8″),114.1
(C-5),115.8(C-3″),116.1(C-5″),117.4(C-8),118.6(C-6),119.9(C-2),124.44(C-6″),
125.8(C-1),128.9(C-1″),143.3(C-4″),144.0(C-7),144.4(C-4),145,7(C-3″),149.1(C-
3),166.3(C-9),172.0(C-9″),175.5(C-1′).
Salviandic acid A: ESI-MS, m/z, 494 [M-H]-,295[M-H-C9H10O5]-.1H-NMR(DMSO-d6,400MHz)δ:
2.75 (1H, dd, J=14.3,8.5Hz, H-7 '), 2.98 (1H, dd, J=14.4/4.5Hz, H-7 '), 4.90 (1H, dd, J=
8.5,6.0Hz, H-8 '), 6.26 (1H, d, J=16.0Hz, H-8), 6.45 (1H, dd, J=8.3,2.0Hz, H-6 "), 6.54
(1H, d, J=8.5Hz, H-5 '), 6.53 (1H, d, J=16.0Hz, H-7 "), 6.63 (1H, d, J=2.0Hz, H-2 '), 6.72
(1H, d, J=8.7Hz, H-5), 7.12 (1H, d, J=8.6Hz, H-6), 6.77 (1H, d, J=8.0Hz, H-5 "), 6.86 (1H,
Dd, J=8.3,2.0Hz, H-6 "), 7.04 (1H, d, J=2.0Hz, H-2 "), 7.13 (1H, d, J=16.0Hz, H-8 ")13C-
NMR(DMSO-d6,100MHz)δ:36.8(C-7′),75.0(C-8′),112.8(C-2″),114.3(C-5),115.3(C-8),
115.7(C-5′),116.4(C-5″),118.6(C-2′),119.0(C-8″),119.1(C-6),119.8(C-6″),123.7
(C-6′),126.5(C-1),129.0(C-2),134.2(C-1′),135.3(C-3),143.6(C-7″),144.8(C-1″),
145.6(C-4′),145.6(C-3′),145.6(C-3″),145.7(C-4″),147.1(C-7),148.4(C-4),166.2
(C-9),171.8(C-9′)..
Protocatechualdehyde: ESI-MS, m/z, 137 [M-H]-,109[M-H-CO]-.1H-NMR(DMSO-d6,400MHz)δ:
9.69 (1H, s, H-7), 7.27 (1H, dd, J=1.3/5.4Hz, H-6), 7.23 (1H, d, J=1.2Hz, H-2), 6.89 (1H,
D, J=5.4Hz, H-5)13C-NMR(DMSO-d6,100MHz)δ:114.7(C-5),115.9(C-2),125.1(C-6),
129.1(C-1),146.4(C-3),153.0(C-4),191.3(-CHO).
Embodiment 2
The NaHCO for being 3.5 with pH by tanshin polyphenolic acid B3Water is configured to the tanshin polyphenolic acid B solution of 45mg/mL, takes the above-mentioned solution of 40mL
It is placed in 50mL subcritical water stainless steel cauldron, after heating furnace reaches 182 DEG C and stablizes, reaction kettle is put into heating furnace, is opened
Beginning timing.Reactor is taken out after 55min rapidly and is put into cooling in ice-water bath, liquid is taken out, is freeze-dried, is obtained rich in red phenol
Sour A crude product.
Salviandic acid A is isolated and purified using high speed adverse current chromatogram
Solvent system is petroleum ether: ethyl acetate: n-butanol: water=2:3:1:9, and upper addition 10mM trifluoroacetic acid is to fix
Phase, it is mobile phase that lower phase, which is 10mM ammonium hydroxide, and high-speed counter-current chromatograph column volume is 300mL, applied sample amount 1.0g, revolving speed 750rpm,
Upper phase is stationary phase, and lower phase is mobile phase, flow velocity 2.0mL/min, stationary phase retention rate 55%, Detection wavelength 280nm.
Specific operating procedure is: preparing solvent system by above-mentioned solvent ratios, is placed in separatory funnel, stands after shaking up
Layering, ready to balance for a period of time afterwards separate upper and lower two-phase, and upper addition 10mM trifluoroacetic acid is stationary phase, and lower phase is 10mM ammonium hydroxide
For mobile phase, takes 1.2g rich in salviandic acid A crude product, be dissolved in 5mL and the upper phase of 10Mm trifluoroacetic acid and 5mL is added to be not added under ammonium hydroxide
It is stand-by in phase.The semi-preparative high-speed counter-current chromatograph developed using Shanghai with field company, it is by plunger pump, sampling valve, purple
Outer detector, recorder and chromatography column (spiral tube formed by polyfluortetraethylene pipe multi-lay winding, capacity 300mL)
Deng composition, sampling valve is made to be in sample introduction state first, stationary phase is filled into chromatography column with pump with certain flow rate, termination of pumping.It opens
Speed control is opened, the chromatographic chromatography column of high velocity stream is rotated forward, when turn up 800rpm, by sample dissolve note
Emitter is injected in the liquid storage tube of counter-current chromatograph sampling valve, and rotation sampling valve is to connect column state, and sample is made to enter chromatography column.
Setting flow rate of mobile phase is 2.0mL/min, starts to pump mobile phase, then receives target component according to detector ultraviolet spectrogram,
Danshensu (36.7mg), salvianolic acid D (9.2mg), salviandic acid A (219.6mg) and protocatechualdehyde (32.1mg) are obtained, HPLC analysis is pure
Degree is 98% or more.
Comparative example 1:
Condition: petroleum ether-ethyl acetate-methanol-water (2:3:3:9), upper phase 10mM trifluoroacetic acid, lower phase 10mM ammonium hydroxide,
Flow velocity: 2mL min-1, sample volume: 1000mg, stationary phase retain: 52%, revolving speed: 800rpm, other conditions and operation all with reality
It applies as in example 1.Separating resulting: appearance time is too fast, and compound is not separated, such as attached drawing 9.
Comparative example 2:
Condition: petroleum ether-ethyl acetate-methanol-water (2:3:1:9), upper phase 10mM trifluoroacetic acid, lower phase 10mM ammonium hydroxide,
Flow velocity: 2mL min-1, sample volume: 900mg, stationary phase retain: 56%, revolving speed: 800rpm, other conditions and operation all with implementation
As in example 1.Separating resulting: separation condition makes moderate progress, and salviandic acid A obtains part sterling, but most of with otherization
It closes object to mix, not efficiently separated yet, such as attached drawing 10.
Comparative example 1 and embodiment 1 are to have changed n-butanol into methanol in solvent system it can be seen from Fig. 9 and Figure 10,
And the ratio of solvent system is changed, results in appearance time too fast, compound is not separated, and comparative example 2 is only
It is only to have changed n-butanol into methanol in solvent system, the ratio of solvent system does not all change, also resulted in and do not obtained
It efficiently separates.
Above-mentioned, although the foregoing specific embodiments of the present invention is described with reference to the accompanying drawings, not protects model to the present invention
The limitation enclosed, those skilled in the art should understand that, based on the technical solutions of the present invention, those skilled in the art are not
Need to make the creative labor the various modifications or changes that can be made still within protection scope of the present invention.
Claims (9)
1. a kind of preparation method of salviandic acid A, characterized in that steps are as follows:
(1) tanshin polyphenolic acid B is configured to the solution of 35-45mg/mL, with NaOH or NaHCO3Water management pH is 3.5-4.5, is placed in Asia
In critical reaction kettle, after heating furnace reaches 170 DEG C -190 DEG C and stablizes, reaction kettle is put into heating furnace, after 50min-70min
It takes out reaction kettle and is put into ice-water bath or cold water punching cooling, liquid is taken out, is freeze-dried, obtains rich in salviandic acid A crude product；
(2) isolate and purify salviandic acid A using high speed adverse current chromatogram: solvent system is petroleum ether: ethyl acetate: n-butanol: water=
2:3:1:9, upper addition 10mM trifluoroacetic acid are stationary phase, and lower phase is that 10mM ammonium hydroxide is mobile phase, high-speed counter-current chromatograph cylinder
Product is 200-400mL, applied sample amount 1.0-1.2g, revolving speed 600-1000rpm, flow velocity 1-4mL/min, Detection wavelength 280nm.
2. preparation method as described in claim 1, it is characterized in that: tanshin polyphenolic acid B is configured to 40mg/mL in the step (1)
Solution, use NaHCO3Water management pH is 4.0.
3. preparation method as described in claim 1, it is characterized in that: heating furnace reaches 180 DEG C in the step (1).
4. preparation method as described in claim 1, it is characterized in that: taking out reactor rapidly simultaneously after 60min in the step (1)
It is put into ice-water bath cooling.
5. preparation method as described in claim 1, it is characterized in that: the step (2) high speed counter-current chromatograph column volume is
300mL。
6. preparation method as described in claim 1, it is characterized in that: applied sample amount 1.2g in the step (2).
7. preparation method as described in claim 1, it is characterized in that: revolving speed 800rpm in the step (2).
8. preparation method as described in claim 1, it is characterized in that: flow velocity 2.0mL/min in the step (2).
9. one kind has expansion coronary artery, platelet aggregation-against, improves blood circulation, prevents thrombosis, atherosclerotic plaque
Block forms, promotes the preparation method of the drug of pathological change recovery, it is characterized in that: including any system of claim 1-8
The step of Preparation Method.
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| CN201610806533.8A CN106431915B (en) | 2016-09-07 | 2016-09-07 | A kind of preparation method of salviandic acid A |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1995027A (en) * | 2006-12-30 | 2007-07-11 | 山东省分析测试中心 | Separating preparation process of salvianolic acid B |
| CN102249920A (en) * | 2011-05-30 | 2011-11-23 | 上海朗萨医药科技有限公司 | Preparation method of high-purity salvianolic acid A |
| CN105085266A (en) * | 2014-05-14 | 2015-11-25 | 南京虹桥医药技术研究所 | Method for preparing salvianolic acid A from a plurality of salvia plants |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1995027A (en) * | 2006-12-30 | 2007-07-11 | 山东省分析测试中心 | Separating preparation process of salvianolic acid B |
| CN102249920A (en) * | 2011-05-30 | 2011-11-23 | 上海朗萨医药科技有限公司 | Preparation method of high-purity salvianolic acid A |
| CN105085266A (en) * | 2014-05-14 | 2015-11-25 | 南京虹桥医药技术研究所 | Method for preparing salvianolic acid A from a plurality of salvia plants |
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| 亚临界水中化学反应的研究进展;戚聿妍 等;《化工进展》;20151005;第34卷(第10期);第3557-3562页 |
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