CN1830947A - Method for extracting 'Danfen' phenolic acid-A - Google Patents
Method for extracting 'Danfen' phenolic acid-A Download PDFInfo
- Publication number
- CN1830947A CN1830947A CN 200610012615 CN200610012615A CN1830947A CN 1830947 A CN1830947 A CN 1830947A CN 200610012615 CN200610012615 CN 200610012615 CN 200610012615 A CN200610012615 A CN 200610012615A CN 1830947 A CN1830947 A CN 1830947A
- Authority
- CN
- China
- Prior art keywords
- salvianolic acid
- extracting
- extraction
- extracting method
- method steps
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims description 63
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 title 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000003960 organic solvent Substances 0.000 claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- 240000007164 Salvia officinalis Species 0.000 claims abstract description 12
- 239000002253 acid Substances 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims abstract description 7
- 235000005412 red sage Nutrition 0.000 claims abstract description 7
- YMGFTDKNIWPMGF-QHCPKHFHSA-N Salvianolic acid A Natural products OC(=O)[C@H](Cc1ccc(O)c(O)c1)OC(=O)C=Cc2ccc(O)c(O)c2C=Cc3ccc(O)c(O)c3 YMGFTDKNIWPMGF-QHCPKHFHSA-N 0.000 claims description 55
- YMGFTDKNIWPMGF-AGYDPFETSA-N 3-(3,4-dihydroxyphenyl)-2-[(e)-3-[2-[(e)-2-(3,4-dihydroxyphenyl)ethenyl]-3,4-dihydroxyphenyl]prop-2-enoyl]oxypropanoic acid Chemical compound C=1C=C(O)C(O)=C(\C=C\C=2C=C(O)C(O)=CC=2)C=1/C=C/C(=O)OC(C(=O)O)CC1=CC=C(O)C(O)=C1 YMGFTDKNIWPMGF-AGYDPFETSA-N 0.000 claims description 36
- 238000000605 extraction Methods 0.000 claims description 32
- 239000000243 solution Substances 0.000 claims description 25
- YMGFTDKNIWPMGF-UCPJVGPRSA-N Salvianolic acid A Chemical compound C([C@H](C(=O)O)OC(=O)\C=C\C=1C(=C(O)C(O)=CC=1)\C=C\C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 YMGFTDKNIWPMGF-UCPJVGPRSA-N 0.000 claims description 19
- 229930183842 salvianolic acid Natural products 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 13
- 239000012141 concentrate Substances 0.000 claims description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 238000004587 chromatography analysis Methods 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 238000000638 solvent extraction Methods 0.000 claims description 8
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 7
- 239000012071 phase Substances 0.000 claims description 7
- 239000011347 resin Substances 0.000 claims description 7
- 229920005989 resin Polymers 0.000 claims description 7
- 239000000945 filler Substances 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 6
- 235000014347 soups Nutrition 0.000 claims description 6
- 235000017276 Salvia Nutrition 0.000 claims description 5
- 239000000284 extract Substances 0.000 claims description 5
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 239000000796 flavoring agent Substances 0.000 claims description 3
- 235000019634 flavors Nutrition 0.000 claims description 3
- 238000012856 packing Methods 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000004793 Polystyrene Substances 0.000 claims description 2
- 239000008346 aqueous phase Substances 0.000 claims description 2
- 229940043232 butyl acetate Drugs 0.000 claims description 2
- 230000006837 decompression Effects 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 229940093499 ethyl acetate Drugs 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000003456 ion exchange resin Substances 0.000 claims description 2
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 229920002223 polystyrene Polymers 0.000 claims description 2
- 229940090181 propyl acetate Drugs 0.000 claims description 2
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000012360 testing method Methods 0.000 claims description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 230000001105 regulatory effect Effects 0.000 abstract description 4
- 238000000746 purification Methods 0.000 description 5
- WTPPRJKFRFIQKT-UHFFFAOYSA-N 1,6-dimethyl-8,9-dihydronaphtho[1,2-g][1]benzofuran-10,11-dione;1-methyl-6-methylidene-8,9-dihydro-7h-naphtho[1,2-g][1]benzofuran-10,11-dione Chemical compound O=C1C(=O)C2=C3CCCC(=C)C3=CC=C2C2=C1C(C)=CO2.O=C1C(=O)C2=C3CCC=C(C)C3=CC=C2C2=C1C(C)=CO2 WTPPRJKFRFIQKT-UHFFFAOYSA-N 0.000 description 4
- 244000132619 red sage Species 0.000 description 4
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000007965 phenolic acids Chemical class 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 235000009048 phenolic acids Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- SNKFFCBZYFGCQN-UHFFFAOYSA-N 2-[3-[3-[1-carboxy-2-(3,4-dihydroxyphenyl)ethoxy]carbonyl-2-(3,4-dihydroxyphenyl)-7-hydroxy-2,3-dihydro-1-benzofuran-4-yl]prop-2-enoyloxy]-3-(3,4-dihydroxyphenyl)propanoic acid Chemical compound C=1C=C(O)C=2OC(C=3C=C(O)C(O)=CC=3)C(C(=O)OC(CC=3C=C(O)C(O)=CC=3)C(O)=O)C=2C=1C=CC(=O)OC(C(=O)O)CC1=CC=C(O)C(O)=C1 SNKFFCBZYFGCQN-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- SNKFFCBZYFGCQN-VWUOOIFGSA-N Lithospermic acid B Natural products C([C@H](C(=O)O)OC(=O)\C=C\C=1C=2[C@H](C(=O)O[C@H](CC=3C=C(O)C(O)=CC=3)C(O)=O)[C@H](OC=2C(O)=CC=1)C=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 SNKFFCBZYFGCQN-VWUOOIFGSA-N 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- STCJJTBMWHMRCD-UHFFFAOYSA-N salvianolic acid B Natural products OC(=O)C(Cc1ccc(O)c(O)c1)OC(=O)C=Cc2cc(O)c(O)c3OC(C(C(=O)OC(Cc4ccc(O)c(O)c4)C(=O)O)c23)c5ccc(O)c(O)c5 STCJJTBMWHMRCD-UHFFFAOYSA-N 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
Landscapes
- Medicines Containing Plant Substances (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A process for preparing danshinolic acid A from red sage root includes such steps as extracting in water or alcohol, concentrating, high-temp and -pressure reaction, purifying by chromatographic column, regulating pH value, extracting in organic solvent, concentrating and drying.
Description
Technical field
The present invention relates to a kind of extracting method of pharmaceutical cpd, especially a kind of extracting method that from the red sage root, extracts salvianolic acid A.
Background technology
The red sage root is the most frequently used one of the medicinal material of invigorating blood circulation, and is used for the treatment of cardiovascular and cerebrovascular diseases such as stenocardia, hypertension, coronary heart disease and apoplexy.Nearly two more than ten years, the main active ingredient pressure differential self research of the red sage root is more active.Experiment in vivo and vitro shows that pressure differential self also can be treated multiple disease except being used for the treatment of cardiovascular and cerebrovascular diseases, as tumour, hepatopathy, ephrosis, peptic ulcer etc.Most of investigator is a target with total phenolic acid or with the salvianolic acid B, and ignores the lower and active stronger salvianolic acid A of content.
Went through 20 years, " basis and the clinical study of Radix Salviae Miltiorrhizae total phenolic acids treatment cerebro-vascular diseases " project of finishing by institute of Materia Medica,Chinese Academy of Medical Sciences etc. on December 30th, 2005 by appraisal of scientific and technological achievements by sanitation Ministry tissue.
People such as Zhen Yongsu have carried out big quantity research to the activity of salvianolic acid A, find that salvianolic acid A is used for the treatment of the effect of tumour, it is characterized in that the nucleoside transporting of tumour cell is had restraining effect, and tumour cell is had lethal effect, can strengthen the curative effect of cancer therapy drug.
Chinese patent CN1384090A disclosed the extracting method of water extract-alcohol precipitation after resin in 2002, and this technology increases alcohol precipitation makes phenolic acids loss 30%.Chinese patent CN03132382. disclosed and adopts water temperature centrifugal, ultrafiltration, acid adjustment, organic solvent extraction to prepare the method for salvianolic acid A again through reversed phase column chromatography in 2002.Because salvianolic acid A content in medicinal material is very low, sometimes even do not have, so the salvianolic acid A extraction yield is very low, causes difficulty for big production, in the big production of industry certain limitation is arranged, and therefore can not fundamentally solve the industrial problems of salvianolic acid A.
Summary of the invention
The present invention be directed to the deficiency that above-mentioned prior art exists, provide a kind of salvianolic acid A extraction yield height, purity good, stable performance, the extracting method of a kind of salvianolic acid A that production cost is low.
For achieving the above object, the technique means that the present invention taked is: a kind of extracting method of salvianolic acid A may further comprise the steps:
Step 1, in the red sage root of salvia piece or pulverizing, add proper amount of solvent, after extracting, carry out solid-liquid separation as solvent;
Step 2, extracting solution is carried out high-temperature high-voltage reaction;
Step 3, with the soup that step 2 obtains, join in the chromatography column, behind the water wash-out, use the eluent wash-out, after testing, collect highly purified salvianolic acid A solution, the decompression or normal pressure be concentrated into the elutriant organic solvent-free;
Step 4, the solution that step 3 is obtained are transferred PH 2～6 with acid, through chloroform or ether class organic solvent extraction, discard organic solvent mutually after, add the acetate esters organic solvent extraction at aqueous phase, will contain the soup of acetate esters organic solvent, concentrate drying.
When the proper amount of solvent that adds in this method steps one was water, extracting temperature was 0～100 ℃, extracted and selected for use supersound extraction, refluxing extraction or dynamic countercurrent to extract, and solid-liquid separation adopts filtration, natural subsidence or centrifugal.When adopting supersound extraction, the temperature of extraction is not more than 60 ℃, and when adopting dynamic countercurrent to extract, the temperature of extraction is 50～95 ℃.
When the proper amount of solvent that adds in the step 1 is water, carry out in this method steps two also can earlier extracting solution being concentrated before the high-temperature high-voltage reaction.
In addition, the proper amount of solvent that adds in this method steps one is an aqueous ethanolic solution, and alcohol concn is 10～80%, and extraction can select for use supersound extraction, refluxing extraction or diacolation to extract; Solid-liquid separation adopts filtration, natural subsidence or centrifugal.
When the proper amount of solvent that adds in the step 1 is aqueous ethanolic solution, carries out also extracting solution to be carried out before the high-temperature high-voltage reaction normal pressure in this method steps two and concentrate or be evaporated to and do not have the alcohol flavor.
In the aforesaid method step 2, the high-temperature high-voltage reaction condition is the pressure of 0.01Mpa～0.25MPa, and high temperature is at 101～140 ℃, and the reaction times is 0.5～24 hour.
Filler in this method steps three in the chromatography column is macroporous resin class, ion exchange resin, ephadex-20 gel, C18 bonded-phase chromatography post or C8 bonded-phase chromatography column packing, the best filler macroporous resin of polystyrene skeleton; Eluent adopts the aqueous solution of ethanol, methyl alcohol, acetone or acetonitrile.
In this method steps four, the acid of transferring pH value to use can be various organic acids or mineral acid; The acetate esters organic solvent is ethyl acetate, propyl acetate or butylacetate; Concentrate and adopt concentrating under reduced pressure or normal pressure to concentrate; Dry employing vacuum-drying or lyophilize; The acetate esters extraction liquid can adopt single stage method drying or two-step approach drying, and single stage method adopts the concentrating under reduced pressure drying to obtain the salvianolic acid A finished product; Two-step approach is to concentrate under normal pressure or reduced pressure earlier, adopts method dryings such as vacuum-drying or lyophilize to obtain the salvianolic acid A finished product then.
The present invention has overcome defective and the deficiency in the extracting method of existing salvianolic acid A, and the amount of final extract reaches more than 3.5 ‰, and salvianolic acid A content reaches more than 80% in the extract, therefore, salvianolic acid A yield height, purity is good, and stable performance, production cost are low.
Embodiment
The extracting method of one one kinds of salvianolic acid As of embodiment:
Get DANSHEN KELI 250kg, add 60% ethanol ultrasonic extraction 3 times of 6 times of amounts, each 20 minutes, 30 ℃ of supersound extraction temperature.United extraction liquid, it is centrifugal to cross tripodia, and centrifugate adopts concentrating under reduced pressure, and temperature is controlled at 60 ℃, is concentrated to 1: 1, and concentrated solution is put in the reactor 120 ℃ of reactions 8 hours.Get above-mentioned soup and cross macroporous resin column, applied sample amount (calculating with the crude drug dry weight) and macroporous resin amount were than 1: 5, remove impurity with the water flushing of 10 times of column volumes earlier, the back is that impurity is removed in 20% ethanol water flushing with 10 times of column volume concentration, is that 40% aqueous ethanolic solution washes with concentration again, does not have salvianolic acid A to Liquid Detection, collect elutriant, 60 ℃ are evaporated to nothing alcohol flavor, with salt acid for adjusting pH value to 2 ~ 4, get supernatant liquor, with the chloroform extraction of 1 times of supernatant liquor amount volume 1 time, discard the chloroform phase, water adds 1.5 times of amount volumes of acetic acid ethyl esters extraction 3 times, combined ethyl acetate phase, concentrating under reduced pressure, make soup to the thick paste shape, lyophilize gets salvianolic acid A.
The extracting method of 21 kinds of salvianolic acid As of embodiment: basic identical with embodiment one, different is the water supersound extraction.Specific as follows:
DANSHEN KELI adds the water of 6 times of amounts, supersound extraction 3 times, each 40 minutes, 40 ℃ of ultrasonic temperature.
The extracting method of 31 kinds of salvianolic acid As of embodiment: basic identical with embodiment two, different is that ultrasonic temperature is 0 ℃, and is specific as follows:
DANSHEN KELI adds the water of 6 times of amounts, supersound extraction 3 times, each 90 minutes, 0 ℃ of ultrasonic temperature.
The extracting method of 41 kinds of salvianolic acid As of embodiment: basic identical with embodiment three, different is that ultrasonic temperature is 1 ℃.
The extracting method of embodiment kind on May Day salvianolic acid A: basic identical with embodiment two, different is that ultrasonic temperature is 60 ℃, and is specific as follows:
DANSHEN KELI adds the water of 6 times of amounts, supersound extraction 3 times, each 10 minutes, 60 ℃ of ultrasonic temperature.
The extracting method of 61 kinds of salvianolic acid As of embodiment: basic identical with embodiment one, different is that the aqueous ethanolic solution diacolation extracts.Specific as follows:
Red sage root meal, the diacolation bucket of packing into was soaked in the 60% aqueous ethanolic solution sealing that adds 1.5 times of amounts 6 hours, dress is real, and 60% aqueous ethanolic solution is not stopped to add in the upper end, opens valve below and collects percolate, when collecting 6 ~ 7 times of amount medicinal material volumes, do not have salvianolic acid A, judge that diacolation stops to Liquid Detection.
The extracting method of embodiment kind July 1st salvianolic acid A: basic identical with embodiment one, different is the aqueous ethanolic solution refluxing extraction.
Salvia piece adds the aqueous ethanolic solution of 8 times of amounts, refluxing extraction 3 times, each 1.5 hours.
The extracting method of embodiment Aug. 1st kind salvianolic acid A: basic identical with embodiment one, different is the water refluxing extraction.
Salvia piece adds the water of 10 times of amounts, refluxing extraction 3 times, each 1 hour.
The extracting method of 91 kinds of salvianolic acid As of embodiment: basic identical with embodiment one, different is hydrodynamic(al) attitude countercurrent extraction.
Salvia piece, 80 ℃ of Heating temperatures, flow velocity is jar/40min.
The extracting method of 11 kinds of salvianolic acid As of embodiment: basic identical with embodiment nine, different is that Heating temperature is 50 ℃.
The extracting method of 11 kinds of salvianolic acid As of embodiment: basic identical with embodiment nine, different is that Heating temperature is 95 ℃.
The extracting method of 12 kinds of salvianolic acid As of embodiment: basic identical with embodiment two, different is that extracting solution does not concentrate and directly carries out high-temperature high-voltage reaction.
The extracting method of 13 kinds of salvianolic acid As of embodiment: basic identical with embodiment eight, different is that extracting solution does not concentrate and directly carries out high-temperature high-voltage reaction.
The extracting method of 14 kinds of salvianolic acid As of embodiment: basic identical with embodiment nine, different is that extracting solution does not concentrate and directly carries out high-temperature high-voltage reaction.
The extracting method of embodiment kind salvianolic acid A on ten May Day: basic identical with embodiment one, different is that column purification adopts the C18 bonding as chromatographic column filler.
The extracting method of 16 kinds of salvianolic acid As of embodiment: basic identical with embodiment one, different is that column purification adopts the C8 bonding as chromatographic column filler.
The extracting method of embodiment kind salvianolic acid A ten July 1st: basic identical with embodiment one, different is column purification, eluting solvent methanol aqueous solution.
The extracting method of 18 kinds of salvianolic acid As of embodiment: basic identical with embodiment one, different is column purification, eluting solvent aqueous acetone solution.
The extracting method of 19 kinds of salvianolic acid As of embodiment: basic identical with embodiment one, different is column purification, eluting solvent acetonitrile solution.
The extracting method of 21 kinds of salvianolic acid As of embodiment: basic identical with embodiment one, different is that the pH value is regulated and adopted sulfuric acid.
The extracting method of 21 kinds of salvianolic acid As of embodiment: basic identical with example one, different is to transfer pH value to 2-3 during the adjust pH organic solvent extraction.
The extracting method of 22 kinds of salvianolic acid As of embodiment: basic identical with example one, different is, adopts ether when regulating the pH organic solvent extraction earlier, after use ethyl acetate extraction.
The extracting method of 23 kinds of salvianolic acid As of embodiment: basic identical with example one, different is, adopts chloroform when regulating the pH organic solvent extraction earlier, after use n-butyl acetate extraction.
Claims (10)
1, a kind of extracting method of salvianolic acid A is characterized in that this method may further comprise the steps:
Step 1, in the red sage root of salvia piece or pulverizing, add proper amount of solvent, after extracting, carry out solid-liquid separation as solvent;
Step 2, extracting solution is carried out high-temperature high-voltage reaction;
Step 3, with the soup that step 2 obtains, join in the chromatography column, behind the water wash-out, use the eluent wash-out, after testing, collect highly purified salvianolic acid A solution, the decompression or normal pressure be concentrated into the elutriant organic solvent-free;
Step 4, the solution that step 3 is obtained are transferred PH2～6 with acid, through chloroform or ether class organic solvent extraction, discard organic solvent mutually after, add the acetate esters organic solvent extraction at aqueous phase, will contain the soup of acetate esters organic solvent, concentrate drying.
2, the extracting method of a kind of salvianolic acid A according to claim 1, it is characterized in that the proper amount of solvent that adds in this method steps one is a water, extracting temperature is 0～100 ℃, extraction selects for use supersound extraction, refluxing extraction or dynamic countercurrent to extract, and solid-liquid separation adopts filtration, natural subsidence or centrifugal.
3, the extracting method of a kind of salvianolic acid A according to claim 2 is characterized in that: the temperature of supersound extraction is not more than 60 ℃ in this method steps one; The temperature that dynamic countercurrent extracts is 50～95 ℃.
4, the extracting method of a kind of salvianolic acid A according to claim 2 is characterized in that: carry out in this method steps two before the high-temperature high-voltage reaction extracting solution being concentrated.
5, the extracting method of a kind of salvianolic acid A according to claim 1 is characterized in that the proper amount of solvent that adds in this method steps one is an aqueous ethanolic solution, and alcohol concn is 10～80%, and extraction can select for use supersound extraction, refluxing extraction or diacolation to extract; Solid-liquid separation adopts filtration, natural subsidence or centrifugal.
6, the extracting method of a kind of salvianolic acid A according to claim 5 is characterized in that carrying out in this method steps two also extracting solution to be carried out before the high-temperature high-voltage reaction normal pressure and concentrates or be evaporated to and do not have the alcohol flavor.
7, according to the extracting method of claim 1 or 4 or 6 each described a kind of salvianolic acid As, it is characterized in that in this method steps two, the high-temperature high-voltage reaction condition is the pressure of 0.01Mpa～0.25MPa, and high temperature is at 101～140 ℃, and the reaction times is 0.5～24 hour.
8, the extracting method of a kind of salvianolic acid A according to claim 1, it is characterized in that the filler in the chromatography column is macroporous resin class, ion exchange resin, Sephadex-20 gel, C18 bonded-phase chromatography post or C8 bonded-phase chromatography column packing in this method steps three, eluent adopts the aqueous solution of ethanol, methyl alcohol, acetone or acetonitrile.
9, the extracting method of a kind of salvianolic acid A according to claim 8 is characterized in that the filler in the chromatography column is the macroporous resin of polystyrene skeleton in this method steps three.
10, the extracting method of a kind of salvianolic acid A according to claim 1 is characterized in that in this method steps four, and the acid of transferring pH value to use can be various organic acids or mineral acid; The acetate esters organic solvent is ethyl acetate, propyl acetate or butylacetate; Concentrate and adopt concentrating under reduced pressure or normal pressure to concentrate; Dry employing vacuum-drying or lyophilize.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100126151A CN100420665C (en) | 2006-04-21 | 2006-04-21 | Method for extracting 'Danfen' phenolic acid-A |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100126151A CN100420665C (en) | 2006-04-21 | 2006-04-21 | Method for extracting 'Danfen' phenolic acid-A |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1830947A true CN1830947A (en) | 2006-09-13 |
| CN100420665C CN100420665C (en) | 2008-09-24 |
Family
ID=36993468
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100126151A Expired - Fee Related CN100420665C (en) | 2006-04-21 | 2006-04-21 | Method for extracting 'Danfen' phenolic acid-A |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100420665C (en) |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100462072C (en) * | 2007-01-23 | 2009-02-18 | 北京本草天源药物研究院 | Medicine composition used for injection and its preparing method |
| CN101019878B (en) * | 2007-03-27 | 2010-04-14 | 北京本草天源药物研究院 | Injection medicine composite containing salvianolic acid A and its preparation |
| CN101230003B (en) * | 2007-01-23 | 2010-04-21 | 北京本草天源药物研究院 | Preparation method of salvia miltiorrhiza tanshinoate A |
| CN101006975B (en) * | 2007-02-01 | 2010-05-19 | 北京本草天源药物研究院 | An oral medicine preparation containing salvianolic acid A and extract of panax natoginseng, and its preparation method and application |
| CN101186572B (en) * | 2007-12-19 | 2010-05-19 | 天津大学 | Method for separating and purifying salvianolic acid from red sage root liquid extract by one step |
| CN101006984B (en) * | 2007-02-01 | 2010-05-19 | 北京本草天源药物研究院 | An injection preparation containing salvianolic acid A and extract of panax natoginseng, and its preparation method and application |
| CN101851162A (en) * | 2009-03-30 | 2010-10-06 | 天津天士力制药股份有限公司 | Novel salvianolic acid compound L and preparation method and application thereof |
| CN102212003A (en) * | 2010-04-06 | 2011-10-12 | 山东靶点药物研究有限公司 | Method for purifying salvianolic acid A by using reversed-phase chromatography |
| CN102212001A (en) * | 2010-04-06 | 2011-10-12 | 山东靶点药物研究有限公司 | Compound salvianolic acid F methyl ester and preparation method thereof |
| CN101696166B (en) * | 2007-01-23 | 2012-05-09 | 北京本草天源药物研究院 | Preparation method for danshen root salvianolic acid A |
| CN102531901A (en) * | 2010-12-25 | 2012-07-04 | 上海绿谷制药有限公司 | Preparation method for salvianolic acid A |
| CN103242161A (en) * | 2013-05-17 | 2013-08-14 | 成都科源生物技术有限公司 | Method for preparing salvianolic acid A |
| CN103570548A (en) * | 2013-10-17 | 2014-02-12 | 浙江永宁药业股份有限公司 | Preparation method of salvinaolic acid A |
| CN108872440A (en) * | 2018-08-11 | 2018-11-23 | 中山市永恒化工新材料研究院有限公司 | The measurement method of phenol content in a kind of water |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1229324C (en) * | 2001-09-26 | 2005-11-30 | 中国医学科学院药物研究所 | Extraction process of tanshin general phenolic acid and its prepn and use |
| CN1305866C (en) * | 2003-08-19 | 2007-03-21 | 江苏扬子江药业集团有限公司 | Method of extracting phenolic components from chinese medicine red sage root and its freeze dried powder injection agent |
-
2006
- 2006-04-21 CN CNB2006100126151A patent/CN100420665C/en not_active Expired - Fee Related
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101696166B (en) * | 2007-01-23 | 2012-05-09 | 北京本草天源药物研究院 | Preparation method for danshen root salvianolic acid A |
| CN101230003B (en) * | 2007-01-23 | 2010-04-21 | 北京本草天源药物研究院 | Preparation method of salvia miltiorrhiza tanshinoate A |
| CN100462072C (en) * | 2007-01-23 | 2009-02-18 | 北京本草天源药物研究院 | Medicine composition used for injection and its preparing method |
| CN101006975B (en) * | 2007-02-01 | 2010-05-19 | 北京本草天源药物研究院 | An oral medicine preparation containing salvianolic acid A and extract of panax natoginseng, and its preparation method and application |
| CN101006984B (en) * | 2007-02-01 | 2010-05-19 | 北京本草天源药物研究院 | An injection preparation containing salvianolic acid A and extract of panax natoginseng, and its preparation method and application |
| CN101019878B (en) * | 2007-03-27 | 2010-04-14 | 北京本草天源药物研究院 | Injection medicine composite containing salvianolic acid A and its preparation |
| CN101186572B (en) * | 2007-12-19 | 2010-05-19 | 天津大学 | Method for separating and purifying salvianolic acid from red sage root liquid extract by one step |
| CN101851162A (en) * | 2009-03-30 | 2010-10-06 | 天津天士力制药股份有限公司 | Novel salvianolic acid compound L and preparation method and application thereof |
| CN101851162B (en) * | 2009-03-30 | 2014-09-17 | 天士力制药集团股份有限公司 | Novel salvianolic acid compound L and preparation method and application thereof |
| CN102212001A (en) * | 2010-04-06 | 2011-10-12 | 山东靶点药物研究有限公司 | Compound salvianolic acid F methyl ester and preparation method thereof |
| CN102212001B (en) * | 2010-04-06 | 2013-11-06 | 山东靶点药物研究有限公司 | Compound salvianolic acid F methyl ester and preparation method thereof |
| CN102212003A (en) * | 2010-04-06 | 2011-10-12 | 山东靶点药物研究有限公司 | Method for purifying salvianolic acid A by using reversed-phase chromatography |
| CN102531901A (en) * | 2010-12-25 | 2012-07-04 | 上海绿谷制药有限公司 | Preparation method for salvianolic acid A |
| CN102531901B (en) * | 2010-12-25 | 2015-04-08 | 苏州雷纳药物研发有限公司 | Preparation method for salvianolic acid A |
| CN103242161A (en) * | 2013-05-17 | 2013-08-14 | 成都科源生物技术有限公司 | Method for preparing salvianolic acid A |
| CN103570548A (en) * | 2013-10-17 | 2014-02-12 | 浙江永宁药业股份有限公司 | Preparation method of salvinaolic acid A |
| CN103570548B (en) * | 2013-10-17 | 2015-07-08 | 浙江永宁药业股份有限公司 | Preparation method of salvinaolic acid A |
| CN108872440A (en) * | 2018-08-11 | 2018-11-23 | 中山市永恒化工新材料研究院有限公司 | The measurement method of phenol content in a kind of water |
| CN108872440B (en) * | 2018-08-11 | 2021-06-29 | 中山市永恒化工新材料研究院有限公司 | Method for measuring content of phenol in water |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100420665C (en) | 2008-09-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1830947A (en) | Method for extracting 'Danfen' phenolic acid-A | |
| CN1164582C (en) | Process for preparing danshen salviandic acid | |
| CN102898539A (en) | Method for subcritical water extraction of ganoderma lucidum polysaccharides | |
| CN106474169B (en) | Celery seed extract, preparation and preparation method thereof | |
| CN102127140A (en) | Method for combinedly extracting Morroniside, dogwood polysaccharide and ursolic acid from dogwood | |
| CN1887849A (en) | Salvianolic acid A preparing process | |
| CN103180334B (en) | Prepare the method for lactone glucoside of Radix Paeoniae and peoniflorin | |
| CN102526127B (en) | Flash type extraction method for active constituents in cordyceps militaris | |
| CN101348474A (en) | Method for preparing salvianolic acid B and tanshinol from Salvia miltiorrhiza stem | |
| CN101041620A (en) | Preparation method of salvia miltiorrhiza tanshinoate A | |
| CN100534508C (en) | Method for extracting effective sites group of smilax China root | |
| CN110917181B (en) | Separation method and application of licochalcone B | |
| CN101121658B (en) | Control method for preparing salvianolic acid A | |
| WO2012019373A1 (en) | Method for preparing paeoniflorin and albiflorin | |
| CN104072456A (en) | Preparation method of high-purity salvianolic acid B | |
| CN101531721B (en) | Industrial preparation method for triterpenoid saponin monomer | |
| CN103059086A (en) | Extraction and purification method of cordycepin from cordyceps militaris solid mediums | |
| CN101703561A (en) | Eucommia bark effective position for treating osteoporosis and preparation method thereof | |
| CN104491048A (en) | Loquat leaf total sesquiterpene extract as well as preparation method and application thereof | |
| CN110950917B (en) | Separation method and application of apiose isoliquiritin | |
| CN103570548B (en) | Preparation method of salvinaolic acid A | |
| CN105294789A (en) | Preparation method of high-purity salidroside | |
| CN111499678A (en) | Preparation and application of traditional Chinese medicine potentilla pentacyclic triterpenoid monomer | |
| CN101647858B (en) | Preparation method of water-soluble extract of red sage root | |
| CN114306122B (en) | Freckle-removing whitening component and application thereof in preparation of cosmetics |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: SUN DEJIE Free format text: FORMER OWNER: WANG GUOZHEN Effective date: 20100728 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 050035 5-1-102, ORIENTAL CITY, NO.25, XUEYUAN ROAD, YUHUA DISTRICT, SHIJIAZHUANG CITY, HEBEI PROVINCE TO: 100039 ROOM 207, UNIT 2, BUILDING 25, QINGTA DONGLI, FENGTAI DISTRICT, BEIJING CITY |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20100728 Address after: 100039 Beijing city Fengtai District East Lane 25 Building 2 room 207 Patentee after: Sun Dejie Address before: 050035 Hebei Province, Shijiazhuang city Yuhua District School Road No. 25 Oriental City 5-1-102 Patentee before: Wang Guozhen |
|
| ASS | Succession or assignment of patent right |
Owner name: BENCAO TIANYUAN PHARMACEUTICAL RESEARCH INST., BEI Free format text: FORMER OWNER: SUN DEJIE Effective date: 20101102 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 100039 ROOM 207, UNIT 2, BUILDING 25, QINGTA DONGLI, FENGTAI DISTRICT, BEIJING TO: 100039 NO.795, DIANCHANG VILLAGE, FENGTAI DISTRICT, BEIJING |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20101102 Address after: 100039 Beijing city Fengtai District indigo plant Village No. 795 Patentee after: Bencao Tianyuan Pharmaceutical Research Inst., Beijing Address before: 100039 Beijing city Fengtai District East Lane 25 Building 2 room 207 Patentee before: Sun Dejie |
|
| DD01 | Delivery of document by public notice | ||
| DD01 | Delivery of document by public notice |
Addressee: Bencao Tianyuan Pharmaceutical Research Inst., Beijing Document name: Notification to Pay the Fees |
|
| DD01 | Delivery of document by public notice | ||
| DD01 | Delivery of document by public notice |
Addressee: Bencao Tianyuan Pharmaceutical Research Inst., Beijing Document name: Notification of Termination of Patent Right |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080924 Termination date: 20180421 |