CN1425659A - Process for preparing danshen salviandic acid - Google Patents

Process for preparing danshen salviandic acid Download PDF

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CN1425659A
CN1425659A CN 02160771 CN02160771A CN1425659A CN 1425659 A CN1425659 A CN 1425659A CN 02160771 CN02160771 CN 02160771 CN 02160771 A CN02160771 A CN 02160771A CN 1425659 A CN1425659 A CN 1425659A
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acid
water
salvianolic acid
extraction
impurity
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CN1164582C (en
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张凤侠
王家平
谈学兵
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Jiangsu New Materia Medica Research Institute Co ltd
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HONGQIAO MEDICINE TECHNOLOGY INST NANJING
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Abstract

The present invention process of danshen salvianolic acid B includes the technological steps of: water extraction; acidifying extractive liquid; column chromatographic separation and purification of salvianolic acid B; and drying. The said process has high extraction rate and high purity, and the extracted product has salvianolic acid B content as high as 90% and stale quality. The present invention is suitable for large scale production.

Description

The preparation method of salvianolic acid B from salvia miltiorrhiza
Technical field
The present invention relates to a kind of preparation method of salvianolic acid B from salvia miltiorrhiza.The structural formula of salvianolic acid B is as follows:
Background technology
The red sage root is one of common drug in China's traditional medicine, and the red sage root has clinical application basis widely as the medicine of treatment cardiovascular disease, and evident in efficacy, and long clinical application history is arranged.Modern pharmacology shows that the pharmacological action of the red sage root mainly is to cardio-cerebrovascular, and energy vasodilation, quickening blood flow are anti-oxidant, microcirculation improvement, change viscosity of blood, anticoagulation, increase blood supply of cardiac muscle amount, oxygen-supplying amount, reduction myocardial consumption of oxygen, anti-hepatic fibrosis etc.Be used for the treatment of cardiovascular disorder and diseases such as hepatic fibrosis, renal failure such as stenocardia, myocardial infarction.
Recent years, many experts use the modern medicine method, in conjunction with multi-disciplinary technique means such as chemistry, molecular biology and cytobiologies, the red sage root have been carried out than systematic research, have obtained a large amount of new understanding and experimental result.Salvia-soluble effective constituent is the important activity composition of the red sage root, is subjected to medical circle and payes attention to greatly.Water soluble component comprises rancinamycin IV, Salvianic acidA and salvianolic acid A, B, C, D, E etc., wherein the composition activity of phenolic acids is the strongest, and is remarkable with the effect of salvianolic acid B especially, confirms through pharmacodynamic experiment, it has significant anti peroxidation of lipid, removes free radical and antithrombotic effect.
Cardiovascular system diseases is the elderly's height morbidity.The developing the salvianolic acid B series product and will do and provide big contribution of success for the mankind prevent and treat cardiovascular diseases.
In recent years, the report about the extraction of the red sage root and the clinical application of red sage compound preparation was a lot.The preparation that the red sage root is used separately is less, generally is to form compound preparation with other medicines to be applied to clinical.A lot of formulations have appearred, as FUFANG DANSHEN PIAN, FUFANG DANSHEN DIWAN, compound Salviae Miltiorrhizae electuary, FUFANG DANSHEN JIAONANG, compound Salviae Miltiorrhizae granule, compound Salviae Miltiorrhizae aerosol, compound injection of red sage root, compound Salviae Miltiorrhizae oral liquid etc.More wide prospect has been opened up in succeeding in developing to the clinical application of the red sage root of these products.But mostly these products are to adopt the old technology of poach alcohol deposition method or ethanol-extracted, the aqueous soluble active constituent major part of the red sage root is lost or destroyed in the leaching process, and oil-soluble impurities content is higher even most its fat-soluble component that kept, wherein based on the TANSHINONES of diterpene quinones.Portioned product has kept more water soluble component, but also mainly is rancinamycin IV, Salvianic acidA, obtains because of its two kinds of compositions more easily separate from medicinal material, and these two kinds of compositions are likely the degradation production of salvianolic acid class, and wherein the toxic side effect of rancinamycin IV is bigger.Nonactive component content is very high in traditional in addition extraction process products obtained therefrom crude drug in whole, and extract weight is generally about 20% of crude drug in whole, and wherein major part is an inactive substance.
Traditional red sage formulation adopts alcohol extracting method more.As according to " red sage root need extract three times in Chinese pharmacopoeia (version was an one in the 2000) FUFANG DANSHEN PIAN, for the first time adds alcohol reflux 1.5 hours, filter, filtrate recycling ethanol, being concentrated into relative density is 1.30; Add for the second time 50% alcohol reflux 1.5 hours, filter; Add water for the third time and refluxed 2 hours, filter.Merge second and third time filtrate, reclaim ethanol, being concentrated into relative density is 1.40, merges with primary concentrated solution, and mixing is made cream clearly.Effective component in red sage in the made FUFANG DANSHEN PIAN of this alcohol extraction process is based on the TANSHINONES of diterpene quinones, and water soluble component is lost substantially.
" pharmaceutical preparation note " (People's Health Publisher 1983.402) disclosed compound injection of red sage root adopts the poach alcohol deposition method, and the red sage root is cleaned back water boiling and extraction three times, filters, and merges three times decocting liquid, is concentrated into every ml and contains medicinal material 1.5~2g.Adding 95% ethanol makes soup contain alcohol amount to reach 75%, place 40 hours after-filtration, filtrate recycling ethanol also is concentrated into every ml and contains medicinal material 3g, adding 95% ethanol at last makes soup contain alcohol amount to reach 85%, place filtration in 4 hours, filtrate recycling ethanol is concentrated into every ml and contains medicinal material 3~5g, pours 13 times distilled water, place 24 hours after-filtration, filtrate recycling ethanol also is concentrated into nothing alcohol flavor.Salvianolic acid B is the four poly-coffic acid compounds that two molecule Salvianic acidAs and the condensation of a part Prolithospermic acid form, extremely unstable at 100, easily be degraded into the caffeinic dehydration of monomer Salvianic acidA and oligomerization, decarboxylate, or being oxidized to rancinamycin IV, Protocatechuic Acid, the effective ingredient salvianolic acid B is most of destroyed behind the poach three times.Different alcohol precipitation concentrations is also bigger to the active constituent content influence of the red sage root, because of phenolic acids composition many forms with salt such as magnesium, potassium, ammonia in plant exist, easily molten and poorly soluble in alcohol in water, 70% alcohol is deposited in when removing impurity, and water-soluble phenolic acids effective ingredient loss amount can reach more than 50%.
Summary of the invention
Technical problem to be solved by this invention is, overcomes the defective that prior art exists, and a kind of preparation method of effective preparation method, especially salvianolic acid B from salvia miltiorrhiza of salvia-soluble composition is provided.
The preparation method of salvianolic acid B from salvia miltiorrhiza of the present invention, its processing step is:
1. water extraction
Under 0~99 ℃ temperature, use the water-soluble components in the water extraction red sage root.
Institute's water can be ordinary water, distilled water, deionized water, reverse osmosis water etc.Can contain micro-acid, alkali, inorganic salt, organic salt, alcohols etc. in the water.
The method of extracting can adopt pickling process, also can adopt percolation process, ultrasonic extraction or microwave extraction method.
Above-mentioned pickling process can be extracted for single-steeping, and also can be repeatedly, dipping extracts.Now the method with twice dipping extraction is that example describes.
Dipping is got red sage root crude drug and is made medicine materical crude slice for the first time, or pulverizes with other proper method, and it is an amount of to add water, and amount of water is generally 6~15 times of medicinal material amount, low temperature or insulation dipping.Can be prior to soaking (soak i.e. dipping herein, both be same meaning) below 40 ℃, and then be heated to 40~99 ℃ of insulation immersions.Suggested design is: amount of water is about 10 times of red sage root amount, and first soak at room temperature 1~4 hour is heated to 40~70 ℃ then, soaks 2~6 hours.Separate extracting solution for the first time.
Flood for the second time, it is an amount of to add water, and amount of water is generally 4~10 times of medicinal material amount.After certain hour is soaked in 40~99 ℃ of insulations, separate obtaining second batch of extracting solution.Suggested design is: amount of water is 8 times of red sage root amount, is heated to 40~70 ℃, soaks 2~6 hours.
Merge extracted twice liquid, adopt the method for filtration, natural sedimentation or centrifuging, tentatively remove the solid impurity in the extracting solution.
Above-mentioned percolation process concrete grammar be get salvia piece or pulverize with other method after the red sage root, be loaded in the diafiltration post or bucket that a synthetic glass makes, limit rim appropriate compacting, about 1/5 volume is reserved in diafiltration post or bucket upper end.Add water to all medicinal material submergences, static immersion 4 hours.Open diafiltration post lower end valve, percolate is slowly flowed out, the amount that per hour flows out percolate is about a times of red sage root dry weight, constantly injects water simultaneously to diafiltration post upper end.With FeCl 3Point sample is observed the content of salvianolic acid B in the percolate, stops diafiltration when more weak to color reaction.
Above-mentioned ultrasonic method concrete grammar is on the basis of pickling process, and leaching process is finished under ultrasonic wave.Ultrasound assisted extraction technique mainly is that the leaching that utilizes cavitation effect of ultrasonic waves to quicken effective ingredients in plant is extracted, and hyperacoustic in addition second-order effect adds mechanical vibration, emulsification, diffusion.Smash, chemical effect etc. also can be quickened diffusion release and abundant and the solvent that desire is extracted composition, is beneficial to extraction.
Above-mentioned microwave method concrete grammar is on the basis of pickling process, and leaching process is finished under microwave.Microwave is the new technology that a kind of recent development of utilizing micro-wave energy to improve extraction yield is got up.Its principle is in microwave field, the difference that absorbs the microwave ability makes some zone of base matter or some component in the extraction system be heated by selectivity, thereby make that be extracted material separates from matrix or system, enter into that specific inductivity is less, the solvent of microwave absorption capacity relative mistake.
2. acidizing extracting liquid
To add inorganic in the above-mentioned steeping fluid or organic acid accent pH, making steeping fluid pH value be 1~6, adopts the method for filtration, natural sedimentation or centrifuging, removes the solid impurity that occurs after the acidifying.Wherein used acid can be hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetate etc.The best is hydrochloric acid or sulfuric acid.
The acidifying purpose is as follows: the salvianolic acid constituents in (1) red sage root mainly exists with the form of salt, and magnesium salts is arranged, and sylvite, ammonia salt etc. are also arranged, and its composition is complicated.After being acidified with acid, become single salvianolic acid B, help the control of quality standard.(2) contain a large amount of colloid class impurity in the steeping fluid, by acidifying, precipitable this class impurity of major part of removing.(3) salvianolic acid B is a slightly acidic class material, and it easily by macroporous resin adsorption, improves the separation and purification effect under acidic conditions.
Above water extraction and acidifying also can realize by one step of method with diluted acid aqueous solution extraction: the red sage root after salvia piece or the pulverizing is directly used diluted acid aqueous solution extraction, the pH value of diluted acid is 1~6, the optional organic acid of kind or the mineral acid of acid, method can be with pickling process or percolation process etc.
3. column chromatography separation, purifying salvianolic acid B
(1) adopts elite filler preparative chromatography post; (2) chromatographic column activation; (3) the water extract with the above-mentioned red sage root adds to chromatographic column, and water, diluted alcohol aqueous solution or water-acetone solvent wash-out is removed impurity; (4) with alcohol-water solution, water-acetone or the acetonitrile-aqueous solution wash-out of alcohols, acetonitrile or proper concn, obtain highly purified salvianolic acid B solution.
In above-mentioned steps (1), elite filler is meant that macroporous resin class, ion exchange resin, MCIGEL-CHP-20P, Sephadex LH-20 gel or C18, C8 bonding equate chromatographic column filler, and suggested design is for to do chromatographic column filler with the macroporous resin of nonpolar or low-pole.
In the above-mentioned steps (2), chromatographic column activatory method can be used the mixture of acetone, methyl alcohol, ethanol, acetonitrile organic solvent or itself and water, also available bases-aqueous solution, or alkali-alcoholic solution activation.
In the above-mentioned steps (3), can contain the acid or the inorganic salt of trace in the wash-out water.
In the above-mentioned steps (3), can singly wash with water and remove impurity, or single acetone-water solvent elution removal of impurity with diluted alcohol aqueous solution or lower concentration; Also can wash with water earlier and take off and then with the acetone-water solvent elution removal of impurity of diluted alcohol aqueous solution or lower concentration.
In the above-mentioned steps (3), the diluted alcohol aqueous solution equal solvent can be the aqueous solution of alcohol such as methyl alcohol, ethanol, propyl alcohol, butanols, also can adopt the aqueous solution of acetonitrile, or their mixture.
In the above-mentioned steps (3), the concentration of diluted alcohol aqueous solution equal solvent is generally below 50%, and commonly used is 10%-40%, the concentration of the most handy 20%-30%, the acetone-water solution of lower concentration acetone content commonly used is generally below 60%, and commonly used is 10%~50%, the most handy 20%~30% concentration.Elution process also can adopt the method for gradient, promptly earlier with the acetone-water eluant solution of lower concentration alcohol or lower concentration, and then with higher concentration alcohol or acetone soln equal solvent wash-out.
In the above-mentioned steps (4), in the acetone-water of proper concn, alcohol-water solution or the acetonitrile-aqueous solution, the organic phase proportion is generally greater than 10%, commonly usedly is 20%-90%, the concentration of the most handy 40%-70%.
4. dry
The drying of elutriant can adopt single stage method, also can adopt two-step approach.Two-step approach is under the condition of decompression or heating soup to be concentrated earlier, adopts spraying drying then, or vacuum-drying, method dryings such as thin film evaporation; Single stage method then is to adopt spraying drying, and methods such as thin film evaporation directly with above-mentioned steps 3 gained elutriant dryings, obtain the salvianolic acid B finished product.
The drying of elutriant also can adopt vacuum lyophilization according to the formulation needs in addition to the above methods; Or be sprayed directly on the solid, powdery pharmaceutical excipient, further dry again.
The preparation method of salvianolic acid B from salvia miltiorrhiza of the present invention owing to use water extraction, has avoided the appearance of water-insoluble compositions such as TANSHINONES; Adopt during extraction to be lower than 100 ℃ temperature, can avoid the destruction of salvianolic acid B; Be acidified with acid and the different salts of salvianolic acid B can be converted into single salvianolic acid B, can precipitate simultaneously and remove the impurity that extracts from red sage root crude drug, the column chromatography separating effect of salvianolic acid B is better under acidic conditions in addition; Owing in the process of wash-out decon, adopted water and lower concentration alcohol equal solvent, the impurity in the extracting solution further removed; In the elution process of effective ingredient salvianolic acid B,, make between other composition of the salvianolic acid B and the red sage root to have obtained separating preferably owing to adopted acetone-water, alcohol-water solution or the acetonitrile-aqueous solution of proper concn.Finally made the higher salvianolic acid B of purity, can make that the content of salvianolic acid B reaches more than 90% in the extract, and steady quality, technical maturity, can scale operation.Compare with other traditional preparation process method that contains red sage formulation, avoided the loss of main effective constituent salvianolic acid B in the red sage root,, make full use of tool such as Chinese material medicine resource and have very important significance improving red sage root curative effect.
Description of drawings
Fig. 1 is the sample chromatogram figure of the salvianolic acid B of embodiment one preparation;
Fig. 2 is salvianolic acid B from salvia miltiorrhiza standard substance color atlass.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail.
Embodiment one: the preparation method of salvianolic acid B, and its processing step is:
1. water extraction (pickling process): get salvia piece, weighing adds water by 10 times of amounts of its weight, soaking at room temperature 4 hours, 3 hours (but agitation as appropriate) of 60 ℃ of insulations then, separation and Extraction liquid; Residue is by 8 water extraordinarily of former salvia piece weight, 2 hours (but agitation as appropriate) of 60 ℃ of insulations, and separation and Extraction liquid merges extracted twice liquid, removes solid impurity in the extracting solution with filter method.
2. extracting solution acidifying: the hydrochloric acid that adds amount of filtrate 1~2% in filtrate is transferred pH, and the limit edged stirs, to pH value of filtrate be 1, left standstill then about two hours, make the abundant sedimentation of precipitate, centrifugal or suction filtration keeps supernatant liquor, discards precipitation.
3. column chromatography separation, purifying salvianolic acid B:
D101 type on the filtrate (production of Tianjin insecticide factory) macroporous resin column, upper prop sample (calculating with the crude drug dry weight) is 1: 4 (W: W) with the ratio of amount of resin, earlier with the water elution removal of impurity of about 30 times of column volumes, be that 30% ethanol aqueous wash removes impurity with the concentration of about 20 times of column volumes again.Be 50% aqueous ethanolic solution wash-out at last with concentration, with FeCl 3The content of salvianolic acid B in the point sample monitoring elutriant in conjunction with high performance liquid phase, elutes fully to salvianolic acid B, collects elutriant.
4. elutriant carries out vacuum concentration under the condition of 60 ℃ of temperature, vacuum tightness-0.1Mpa, reclaims ethanol content of dispersion about 5% to the concentrated solution, and concentrated solution is spray-dried again, makes salvianolic acid B from salvia miltiorrhiza.
Embodiment two: basic identical with embodiment one, different is that the water extraction process is a percolation process.Concrete grammar is as follows:
Get salvia piece, weighing is loaded in the diafiltration post or bucket that a synthetic glass makes, limit rim appropriate compacting, and about 1/5 volume is reserved in diafiltration post or bucket upper end.Add 40 ℃ of warm water to all medicinal material submergences, static immersion 4 hours.Open diafiltration post lower end valve, percolate is slowly flowed out, the amount that per hour flows out percolate is about a times of salvia piece dry weight, constantly injects about 40 ℃ of warm water simultaneously to diafiltration post upper end.With FeCl 3Point sample is observed the content of salvianolic acid B in the percolate, stops diafiltration when more weak to color reaction.
Embodiment three: basic identical with embodiment one, water extraction process that different is is with the 0.01mol/L dilute hydrochloric acid extraction, extracts and acidifying is once finished.
Embodiment four: basic identical with embodiment two, different is that the water extraction process is extracted with the 0.01mol/L dilute sulphuric acid, and extraction and acidifying are once finished.
Embodiment five: basic identical with embodiment one, different is that leaching process adopts ultrasonic extraction, and ultrasonic energy is 0.1 watt.
Embodiment six: basic identical with embodiment one, different is that leaching process adopts microwave extraction method, and microwave energy is 1 watt.
Embodiment seven: basic identical with embodiment one, and when different is the acidizing extracting liquid removal of impurity, be that to transfer pH value of filtrate with sulfuric acid be 1~4.
Embodiment eight: basic identical with embodiment one, and when different is the acidizing extracting liquid removal of impurity, be that to transfer pH value of filtrate with acetic acid be 1~4.
Embodiment nine: basic identical with embodiment one, and when different is the acidizing extracting liquid removal of impurity, be that to transfer pH value of filtrate with phosphoric acid be 1~4.
Embodiment ten: basic identical with embodiment one, and when different is the acidizing extracting liquid removal of impurity, be that to transfer pH value of filtrate with formic acid be 1~4.
Embodiment 11: basic identical with embodiment one, two, three, four, five or six, different is, separate at column chromatography, in the elution process of purifying salvianolic acid B, employing be methanol aqueous solution.
Embodiment 12: this is identical with the embodiment undecyl, and different is, separate at column chromatography, in the elution process of purifying salvianolic acid B, employing be aqueous propanol solution.
Embodiment 13: basic identical with embodiment one, different is, separate at column chromatography, in the elution process of purifying salvianolic acid B, employing be acetonitrile solution.
Embodiment 14: basic identical with embodiment one, different is, separate at column chromatography, in the elution process of purifying salvianolic acid B, employing be aqueous acetone solution.
Embodiment 15: basic identical with embodiment one, different is, separate at column chromatography, in the process of purifying salvianolic acid B, employing be that MCI-GEL CHP-20P makes the chromatogram column packing.
Embodiment 16: basic identical with embodiment one, different is, separate at column chromatography, in the process of purifying salvianolic acid B, employing be that the C18 bonding is made the chromatogram column packing mutually.
Embodiment 17: basic identical with embodiment one, different is, separate at column chromatography, in the process of purifying salvianolic acid B, employing be that ion exchange resin is made the chromatogram column packing.
Embodiment 18: basic identical with embodiment one, different is, separate at column chromatography, in the process of purifying salvianolic acid B, employing be that the C8 bonding is made the chromatogram column packing mutually.
Embodiment 19: basic identical with embodiment one, different is, separate at column chromatography, in the process of purifying salvianolic acid B, employing be that Sephadex LH-20 makes the chromatogram column packing.
The present invention's concrete technical scheme required for protection is not limited to the concrete combination of the expressed technical scheme of the foregoing description.

Claims (7)

1, a kind of preparation method of salvianolic acid B from salvia miltiorrhiza, its processing step is:
Step 1, water extraction
The water extraction process is with red sage root employing pickling process, percolation process, ultrasonic method or the microwave extraction method extraction of salvia piece or pulverizing, isolates the extracting solution that mainly contains red sage root water soluble ingredient; Employing filtration, natural sedimentation or centrifugal method are tentatively removed the solid impurity in the extracting solution;
Step 2, acidizing extracting liquid
Add mineral acid or organic acid accent pH value in extracting solution, making the steeping fluid pH value is 1~6, adopts filtration, natural sedimentation or centrifuging to remove the solid impurity that occurs after the acidifying;
Step 3, column chromatography separate, the purifying salvianolic acid B
A, employing filler preparative chromatography post, the filler that is adopted is macroporous resin class, ion exchange resin, MCIGEL-CHP-20P, SephadexLH-20 gel, C18 bonding phase or C8 bonded-phase chromatography column packing;
B, chromatographic column activation;
C, extracting solution is added to chromatographic column, water, diluted alcohol aqueous solution or water-acetone solvent wash-out is removed impurity;
D, usefulness alcohols, acetone, acetonitrile, alcohol solution, water-acetone soln or acetonitrile-aqueous solution wash-out obtain highly purified salvianolic acid B solution;
Step 4, drying.
2, the preparation method of the described salvianolic acid B from salvia miltiorrhiza of claim 1, it is characterized in that: water extraction and acidizing extracting liquid can be realized by one step of method with diluted acid aqueous solution extraction, be salvia piece or pulverize after the red sage root directly use diluted acid aqueous solution extraction, the pH value of diluted acid is 1~6, and the kind of acid is mineral acid or organic acid; The method of extracting can be pickling process, percolation process, ultrasonic method or microwave extraction method, isolates extracting solution, removes solid impurity in the extracting solution with filtration, natural sedimentation or centrifuging.
3, the preparation method of claim 1 or 2 described salvianolic acid B from salvia miltiorrhiza is characterized in that: step 3, column chromatography are separated, the step C of purifying salvianolic acid B is, and wash with water earlier and remove impurity, and then with diluted alcohol aqueous solution or acetone-water solvent elution, the removal of impurity.
4, the preparation method of claim 1 or 2 described salvianolic acid B from salvia miltiorrhiza, it is characterized in that: step 3, column chromatography separate, the step C of purifying salvianolic acid B is: wash with water earlier and remove impurity, use the acetone soln wash-out of lower concentration alcohol or lower concentration then, use the higher concentration alcohol or the removal of impurity of acetone soln wash-out again.
5, the preparation method of claim 1 or 2 described salvianolic acid B from salvia miltiorrhiza is characterized in that: step 4 adopts a step desiccating method or two step desiccating methods;
One step desiccating method is to adopt spraying drying, and the thin film evaporation method is directly with the elutriant drying of above-mentioned steps 3 gained;
Two-step approach is for evaporating under the condition of decompression or heating earlier, and soup concentrates, and adopts spraying drying then.
6, the preparation method of claim 1 or 2 described salvianolic acid B from salvia miltiorrhiza is characterized in that: step 4 adopts vacuum lyophilization.
7, the preparation method of claim 1 or 2 described salvianolic acid B from salvia miltiorrhiza is characterized in that: step 4 adopts and is sprayed directly on the solid, powdery pharmaceutical excipient, and is further dry again.
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CN100392400C (en) * 2005-11-01 2008-06-04 上海中医药大学 Method for pre processing sample in use for measuring concentration of salvianolic acid B, in biologic body fluid
CN100404040C (en) * 2003-09-19 2008-07-23 天津天士力制药股份有限公司 Medicinal composition for treating cardiopathy and its preparation method and use
CN100420682C (en) * 2006-12-30 2008-09-24 山东省分析测试中心 Separating preparation process of salvianolic acid B
WO2009076869A1 (en) * 2007-12-07 2009-06-25 Lichao Yuan Salvianolic acid of high purity, preparation method and use thereof
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CN101168539B (en) * 2007-12-04 2011-01-19 哈药集团中药二厂 Method for extracting salvianolic acid B
CN101434590B (en) * 2007-11-12 2011-03-23 北京科士蓝医药技术有限公司 Preparation of salvianolic acid B pure product
CN101210002B (en) * 2006-12-27 2011-04-20 中国科学院大连化学物理研究所 Method for separating and preparing salvianolic acid B chemical reference substance
CN1981810B (en) * 2005-12-14 2011-04-27 天津天士力制药股份有限公司 Danshen component, preparation, making method and usage
CN1955171B (en) * 2005-10-28 2011-04-27 山东绿叶天然药物研究开发有限公司 Method for preparing red-rooted salvia phenolic 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
CN102304111A (en) * 2011-07-12 2012-01-04 北京服装学院 Method for extracting and purifying salvianolic acid B with ion exchange fiber
CN101759672B (en) * 2008-11-28 2012-11-14 北京本草天源药物研究院 Salvianolic acid B in radix salviae miltiorrhizae
CN103172601A (en) * 2013-03-04 2013-06-26 西北大学 Method for separating and extracting salvianolic acid B
CN103923043A (en) * 2013-01-15 2014-07-16 天津天士力现代中药资源有限公司 Method for effective preparation of salvianolic acid B extract
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CN105481809A (en) * 2015-12-29 2016-04-13 山东大学 Separation and purification method of salvianolic acid B and preparation method of salvianolic acid B magnesium salt
CN109988133A (en) * 2018-01-03 2019-07-09 天津天士力之骄药业有限公司 A kind of preparation method of danshinolic acid Y

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CN102304111A (en) * 2011-07-12 2012-01-04 北京服装学院 Method for extracting and purifying salvianolic acid B with ion exchange fiber
CN103923043A (en) * 2013-01-15 2014-07-16 天津天士力现代中药资源有限公司 Method for effective preparation of salvianolic acid B extract
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CN103172601A (en) * 2013-03-04 2013-06-26 西北大学 Method for separating and extracting salvianolic acid B
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CN105481809A (en) * 2015-12-29 2016-04-13 山东大学 Separation and purification method of salvianolic acid B and preparation method of salvianolic acid B magnesium salt
CN109988133A (en) * 2018-01-03 2019-07-09 天津天士力之骄药业有限公司 A kind of preparation method of danshinolic acid Y

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