CN1526708A - Coarse taxol product separating and purifying process - Google Patents
Coarse taxol product separating and purifying process Download PDFInfo
- Publication number
- CN1526708A CN1526708A CNA031359167A CN03135916A CN1526708A CN 1526708 A CN1526708 A CN 1526708A CN A031359167 A CNA031359167 A CN A031359167A CN 03135916 A CN03135916 A CN 03135916A CN 1526708 A CN1526708 A CN 1526708A
- Authority
- CN
- China
- Prior art keywords
- taxol
- content
- purification
- product
- sample
- 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
Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention separates and purifies taxol by means of column chromatographic process with macroporous resin, such as AB-8, D101, D201 and AK-9 as fixed phase and polar solvent, such as water solution of ethanol or acetone, as flowing phase, with the effluent flow rate is 0.6-1.5 L/hr. The effluent with taxol content lower than cephalotmannine content is concentrated and dried to obtain intermediate taxol product A; and effluent with taxol content higher than cephalotmannine content is concentrated and dried to obtain intermediate taxol product B. The said process can separate and purify coarse taxol product with 9-20% content to obtain intermediate taxol product with 40-60% content in the yield as high as 80%. The process can eliminate water soluble impurity from the coarse product.
Description
(1) technical field
The present invention relates to the separation and purification field of plant milk extract, specifically is a kind of method from the thick separation and purification of products taxol of taxol.
(2) technical background
Taxol is the most promising cancer therapy drug that recent two decades is found in the world, and cancers such as treatment mammary cancer, ovarian cancer, esophagus cancer, lung cancer, liver cancer are all had good efficacy, cancer cells is had extremely strong lethality, and toxic side effect is minimum.Therefore become the emphasis of present medicine trade research.
Taxol belongs to the diterpenes alkaloid.Beginning most is extraction separation taxol from the natural phant Ramulus et folium taxi cuspidatae.Ramulus et folium taxi cuspidatae is rare species, and natural taxus resource is very limited, and growth of taxol is slow, and natural Ramulus et folium taxi cuspidatae can't be satisfied the requirement that taxol is produced.In order to open up the new source of taxol, people have studied extraction separation taxol, yew cell cultivation production taxol and multiple biosynthesizing, semi-synthetic, complete synthesis taxol technology from the Taxus x media of artificial growth.No matter adopt which kind of technology, because the taxol synthetic ratio is low, cost is high, so taxol costs an arm and a leg.Separation and purification goes out taxol drug from the mixture of the close derivative of multiple structure, homologue in addition, and particularly be very difficult work separating of taxol and Cephalomannine.Yield has lifting slightly in the separation and purification process, promptly mean precious taxol gain and loss what, on the benefit greatest differences will be arranged.So how to improve the separation purifying technique of taxol, be the problem of generally paying attention at present.
Present separation method mainly contains silica gel column chromatography, alumina column chromatography method, and purification process mainly contains reversed phase chromatography method and silica gel column chromatography normal-phase chromatography methods such as C18 column chromatography, fluorophenyl column chromatography.
The patent application of the separation purifying technique of relevant taxol has many, as: the Chinese patent 99815315.X " from containing the method for high yield extraction of taxol material production taxol " of Phytogen Life Sciences Inc's application in 1999 prepares high-purity taxol with the acetone precipitator method, the Chinese patent " a kind of method of taxad alcohol cleaning and purifying " of Fudan University's application in 1998 uses packing normal paraffin drip washing purification of paclitaxel crude product, the Chinese patent of Meiyan Inst. of Biological Engineering, Meixian County's 2001 applications " method of taxol is extracted in enrichment from yew cell nutrient solution filtrate " carries out adsorption and enrichment with macroporous adsorbent resin and test solution thorough mixing, the organic solvent wash-out is concentrated and obtains the enriched material that height contains taxol by the taxol of resin absorption.
The weak point of existing separation purification method is that yield of taxol (promptly from feeding intake, through sequenced technical process, and calculate with the effective ingredient taxol by the output object recovery rate that obtains.The input repeatedly that does not comprise secondary output object) only be 70%; And to use inflammable, explosive or noxious solvent, and harmful as chloroform, methylene dichloride, ethyl acetate, methyl alcohol, acetonitrile etc., contaminate environment, production operation process hazard height; Applied sample amount is little in addition, and silica gel is 150 to 0.9~1.0 with the ratio of sample during general silica gel column chromatography.
(3) summary of the invention
The method that the purpose of this invention is to provide a kind of yield height and production operation safety from the thick separation and purification of products taxol of taxol.
Method from the thick separation and purification of products taxol of taxol of the present invention comprises following step:
1. content of taxol is that 9~20% the thick product of taxol is a material sample;
2. with the macroporous adsorbent resin phase that fixes, macroporous adsorbent resin is 10 ratios with the weight ratio of sample
0.9~1.4;
3. with can with water miscible, concentration is that 40~70% polar solvent aqueous solution are moving phase;
4. use the column chromatography separating and purifying taxol, sample solution is from the chromatography capital of macroporous adsorbent resin
Sample on the end;
5. during the moving phase wash-out, the effluent liquid flow velocity is 0.6~1.5 liter/hour in the chromatography column;
6. by the effluent liquid of time Fractional Collections behind chromatography, per hour collect 1 part, examine to HPLC
Survey taxol concentration stops when being lower than 0.2 mg/ml, on a time period the effluent liquid of Shou Jiing
Be divided into three parts;
7. do not have taxol substantially in the part i effluent liquid, focus on, reclaim solvent;
8. content of taxol is less than Cephalomannine content in the part ii effluent liquid, and concentrate drying gets purple
China fir alcohol intermediates A;
9. content of taxol is greater than Cephalomannine content in the III part effluent liquid, and concentrate drying gets purple
China fir alcohol intermediates B.
The present invention from the advantage of the method for the thick separation and purification of products taxol of taxol is: 1, separation and purification is effective, is that 9~20% the thick purifying products of taxol is the intermediate taxol product that contains taxol 40~60% easily with content of taxol; 2, yield height, the disposable yield of taxol is up to about 80%; 3, operational safety is not used inflammable, explosive or noxious solvent; 4, applied sample amount is big, and the weight ratio of macroporous adsorbent resin and sample is up to 10 to 0.9~1.5, when being general silica gel column chromatography 15 times of the silica gel applied sample amount; 5, can remove water-soluble impurity in the thick product of taxol.
(4) embodiment
Embodiment 1
1. content of taxol is thick product 100 grams of 15.6% taxol, wherein taxol net content 15.6 grams in the material sample;
2. taxol sample raw material is dissolved in 300 milliliter of 95% (V/V) polar solvent ethanol, and adding water to alcohol concn then is 60% (V/V), and sample is about 1 to 5 with the aqueous ethanolic solution weight ratio;
3. macroporous adsorbent resin AB-8 1000 gram, with the weight ratio of sample be 10 to 1, but in the glass chromatography column of 100 centimetres of the 6 centimetres of pack heights of external diameter of packing into;
4. sample from the chromatography column top of macroporous adsorbent resin is about to sample solution and pours in the chromatography column, regulates chromatography column outlet valve, and solution flow rate is 1 liter/hour in the control chromatography column;
5. by the effluent liquid of time Fractional Collections behind chromatography, per hour collect 1 part, when HPLC detection taxol concentration is 0.2 mg/ml, stop;
6. 1~4 part of effluent liquid is a part i, does not wherein have taxol substantially, focuses on, and reclaims solvent;
7. 5~20 parts of effluent liquid are part ii, and wherein content of taxol is less than Cephalomannine content, and concentrate drying gets intermediate taxol product A 8.35 grams, wherein contains taxol 37.4%, and promptly the taxol net content is 3.12 grams, account for 20% of taxol in the raw material;
8. 21~terminated effluent liquid is the III part, wherein content of taxol is greater than Cephalomannine content, and concentrate drying gets intermediate taxol product B 18.2 grams, wherein contains taxol 54.2%, be that the taxol net content is 9.86 grams, account for 63.2% of taxol in the raw material.
Taxol net content among intermediate taxol product A and the B is 12.98 grams altogether, accounts for 83.2% of taxol in the raw material, and promptly the disposable yield of taxol is 83.2%.
Taxol net content average out to 48.9% among intermediate taxol product A and the B.
Embodiment 2
Use macroporous adsorbent resin D101, it is identical with embodiment 1 1.~6. to go on foot other condition;
7. 5~20 parts of effluent liquid are part ii, and wherein content of taxol is less than Cephalomannine content, and concentrate drying gets intermediate taxol product A 8.55 grams, wherein contains taxol 38.5%, and promptly the taxol net content is 3.29 grams, account for 21.09% of taxol in the raw material;
8. 21~terminated effluent liquid is the III part, wherein content of taxol is greater than Cephalomannine content, and concentrate drying gets intermediate taxol product B 17.5 grams, wherein contains taxol 53.5%, be that the taxol net content is 9.36 grams, account for 60.01% of taxol in the raw material.
Taxol net content among intermediate taxol product A and the B is 12.65 grams altogether, accounts for 81.1% of taxol in the raw material, and promptly the disposable yield of taxol is 81.1%.
Taxol net content average out to 48.6% among intermediate taxol product A and the B.
Embodiment 3
Use macroporous adsorbent resin D201, it is identical with embodiment 1 1.~6. to go on foot other condition;
7. 5~20 parts of effluent liquid are part ii, and wherein content of taxol is less than Cephalomannine content, and concentrate drying gets intermediate taxol product A 8.765 grams, wherein contains taxol 40.2%, and promptly the taxol net content is 3.52 grams, account for 22.57% of taxol in the raw material;
8. 21~terminated effluent liquid is the III part, wherein content of taxol is greater than Cephalomannine content, and concentrate drying gets intermediate taxol product B 18.5 grams, wherein contains taxol 50.2%, be that the taxol net content is 9.19 grams, account for 59.53% of taxol in the raw material.
Taxol net content among intermediate taxol product A and the B is 12.81 grams altogether, accounts for 82.1% of taxol in the raw material, and promptly the disposable yield of taxol is 82.1%.
Taxol net content average out to 47.0% among intermediate taxol product A and the B.
Embodiment 4
Use macroporous adsorbent resin AK-9, it is identical with embodiment 1 1.~6. to go on foot other condition;
7. 5~20 parts of effluent liquid are part ii, and wherein content of taxol is less than Cephalomannine content, and concentrate drying gets intermediate taxol product A 8.60 grams, wherein contains taxol 37.8%, and promptly the taxol net content is 3.25 grams, account for 20.84% of taxol in the raw material;
8. 21~terminated effluent liquid is the III part, wherein content of taxol is greater than Cephalomannine content, and concentrate drying gets intermediate taxol product B17.4 gram, wherein contains taxol 51.2%, be that the taxol net content is 8.91 grams, account for 57.11% of taxol in the raw material.
Taxol net content among intermediate taxol product A and the B is 12.16 grams altogether, accounts for 77.9% of taxol in the raw material, and promptly the disposable yield of taxol is 77.9%.
Taxol net content average out to 46.8% among intermediate taxol product A and the B.
Embodiment 5
1. identical with embodiment 1;
2. taxol sample raw material is dissolved in 200 milliliters of polar solvent acetone, and adding water to acetone concentration then is 40% (V/V), and sample is about 1 to 6 with the aqueous acetone solution weight ratio;
3.~5. identical with embodiment 1;
6. 1~2 part of effluent liquid is a part i, does not wherein have taxol substantially, focuses on, and reclaims solvent;
7. 3~6 parts of effluent liquid are part ii, and wherein content of taxol is less than Cephalomannine content, and concentrate drying gets intermediate taxol product A 11.5 grams, wherein contains taxol 30.2%, and promptly the taxol net content is 3.59 grams, account for 23.0% of taxol in the raw material;
8. 17~terminated effluent liquid is the III part, wherein content of taxol is greater than Cephalomannine content, and concentrate drying gets intermediate taxol product B 19.7 grams, wherein contains taxol 48.3%, be that the taxol net content is 9.52 grams, account for 61.0% of taxol in the raw material.
Taxol net content among intermediate taxol product A and the B is 12.11 grams altogether, accounts for 42.0% of taxol in the raw material, and promptly the disposable yield of taxol is 42.0%.
Taxol net content average out to 84.0% among intermediate taxol product A and the B.
Embodiment 6
1. content of taxol is thick product 140 grams of 9.5% taxol, wherein taxol net content 13.3 grams in the material sample;
2. taxol sample raw material is dissolved in 300 milliliter of 95% (V/V) polar solvent ethanol, and adding water to alcohol concn then is 70% (V/V), and sample is about 1 to 4 with the aqueous ethanolic solution weight ratio;
3. identical with embodiment 1;
4. sample from the chromatography column top of macroporous adsorbent resin is about to sample solution and pours in the chromatography column, regulates chromatography column outlet valve, and solution flow rate is 0.6 liter/hour in the control chromatography column;
5. identical with embodiment 1;
6. the 1st part of effluent liquid is part i, wherein do not have taxol substantially, focuses on, and reclaims solvent;
7. 2~16 parts of effluent liquid are part ii, and wherein content of taxol is less than Cephalomannine content, and concentrate drying gets intermediate taxol product A 8.72 grams, wherein contains taxol 30.2%, and promptly the taxol net content is 2.63 grams, account for 19.8% of taxol in the raw material;
8. 16~terminated effluent liquid is the III part, wherein content of taxol is greater than Cephalomannine content, and concentrate drying gets intermediate taxol product B 20.55 grams, wherein contains taxol 41.8%, be that the taxol net content is 8.59 grams, account for 64.59% of taxol in the raw material.
Taxol net content among intermediate taxol product A and the B is 11.22 grams altogether, accounts for 84.4% of taxol in the raw material, and promptly the disposable yield of taxol is 84.4%.
Taxol net content average out to 38.3% among intermediate taxol product A and the B.
Embodiment 7
1. content of taxol is thick product 95 grams of 11.8% taxol, wherein taxol net content 11.2 grams in the material sample;
2. taxol sample raw material is dissolved in 300 milliliter of 95% (V/V) polar solvent ethanol, and adding water to alcohol concn then is 50% (V/V), and sample is about 1 to 6 with the aqueous ethanolic solution weight ratio;
3. identical with embodiment 1;
4. sample from the chromatography column top of macroporous adsorbent resin is about to sample solution and pours in the chromatography column, regulates chromatography column outlet valve, and solution flow rate is 1.5 liters/hour in the control chromatography column;
5. identical with embodiment 1;
6. 1~6 part of effluent liquid is a part i, does not wherein have taxol substantially, focuses on, and reclaims solvent;
7. 7~23 parts of effluent liquid are part ii, and wherein content of taxol is less than Cephalomannine content, and concentrate drying gets intermediate taxol product A 4.59 grams, wherein contains taxol 36.1%, and promptly the taxol net content is 1.66 grams, account for 14.79% of taxol in the raw material;
8. 24~terminated effluent liquid is the III part, wherein content of taxol is greater than Cephalomannine content, and concentrate drying gets intermediate taxol product B 11.98 grams, wherein contains taxol 56.2%, be that the taxol net content is 6.73 grams, account for 60.1% of taxol in the raw material.
Taxol net content among intermediate taxol product A and the B is 8.39 grams altogether, accounts for 74.9% of taxol in the raw material, and promptly the disposable yield of taxol is 74.9%.
Taxol net content average out to 50.6% among intermediate taxol product A and the B.
Embodiment 8
1. content of taxol is thick product 120 grams of 18.6% taxol, wherein taxol net content 22.32 grams in the material sample;
2. taxol sample raw material is dissolved in 300 milliliter of 95% (V/V) polar solvent ethanol, and adding water to alcohol concn then is 65% (V/V), and sample is about 1 to 4.5 with the aqueous ethanolic solution weight ratio;
3. identical with embodiment 1;
4. sample from the chromatography column top of macroporous adsorbent resin is about to sample solution and pours in the chromatography column, regulates chromatography column outlet valve, and solution flow rate is 1.2 liters/hour in the control chromatography column;
5. identical with embodiment 1;
6. 1~3 part of effluent liquid is a part i, does not wherein have taxol substantially, focuses on, and reclaims solvent;
7. 4~18 parts of effluent liquid are part ii, wherein content of taxol is less than Cephalomannine content, and concentrate drying gets intermediate taxol product A 11.31 grams, wherein contains taxol 38.3%, be that the taxol net content is 4.33 grams, account for 19.41% of taxol in the raw material;
8. 19~terminated effluent liquid is the III part, wherein content of taxol is greater than Cephalomannine content, and concentrate drying gets intermediate taxol product B 27.34 grams, wherein contains taxol 52.9%, be that the taxol net content is 14.46 grams, account for 64.8% of taxol in the raw material.
Taxol net content among intermediate taxol product A and the B is 18.79 grams altogether, accounts for 84.2% of taxol in the raw material, and promptly the disposable yield of taxol is 84.2%.
Taxol net content average out to 48.6% among intermediate taxol product A and the B.
Claims (9)
1 one kinds of methods from the thick separation and purification of products taxol of taxol comprise following step:
1. content of taxol is that 9~20% the thick product of taxol is a material sample;
2. with the macroporous adsorbent resin phase that fixes, macroporous adsorbent resin is 10 to 0.9~1.4 with the weight ratio of sample;
3. with can with water miscible, concentration is that 40~70% polar solvent aqueous solution are moving phase;
4. use the column chromatography separating and purifying taxol, sample solution sample from the chromatography column top of macroporous adsorbent resin;
5. during the moving phase wash-out, the effluent liquid flow velocity is 0.6~1.5 liter/hour in the chromatography column;
6. by the effluent liquid of time Fractional Collections behind chromatography, per hour collect 1 part, when HPLC detection taxol concentration is lower than 0.2 mg/ml, stop;
7. content of taxol is less than Cephalomannine content in the effluent liquid, and concentrate drying gets intermediate taxol product A;
8. content of taxol is greater than Cephalomannine content in the effluent liquid, and concentrate drying gets intermediate taxol product B.
2 methods from the thick separation and purification of products taxol of taxol as claimed in claim 1 is characterized by:
Described macroporous adsorbent resin wherein is AB-8 or D101 or D201 or AK-9.
3 methods from the thick separation and purification of products taxol of taxol as claimed in claim 1 or 2 is characterized by:
Wherein said polar solvent is ethanol or acetone.
4 as each described method from the thick separation and purification of products taxol of taxol in the claim 1 to 3, it is characterized by:
The concentration of the wherein said polar solvent aqueous solution is 55~65%.
5 methods from the thick separation and purification of products taxol of taxol as claimed in claim 4 is characterized by:
The concentration of the wherein said polar solvent aqueous solution is 58~62%.
6 as each described method from the thick separation and purification of products taxol of taxol in the claim 1 to 5, it is characterized by:
Wherein said macroporous adsorbent resin is 10 to 0.9~1.2 with the weight ratio of sample.
7 methods from the thick separation and purification of products taxol of taxol as claimed in claim 6 is characterized by:
Wherein said macroporous adsorbent resin is 10 to 0.95~1.05 with the weight ratio of sample.
8 as each described method from the thick separation and purification of products taxol of taxol in the claim 1 to 7, it is characterized by:
The effluent liquid flow velocity is 0.8~1.2 liter/hour in the wherein said chromatography column.
9 methods from the thick separation and purification of products taxol of taxol as claimed in claim 8 is characterized by:
The effluent liquid flow velocity is 0.9~1.1 liter/hour in the wherein said chromatography column.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 03135916 CN1244568C (en) | 2003-09-22 | 2003-09-22 | Coarse taxol product separating and purifying process |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 03135916 CN1244568C (en) | 2003-09-22 | 2003-09-22 | Coarse taxol product separating and purifying process |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1526708A true CN1526708A (en) | 2004-09-08 |
CN1244568C CN1244568C (en) | 2006-03-08 |
Family
ID=34286366
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 03135916 Expired - Fee Related CN1244568C (en) | 2003-09-22 | 2003-09-22 | Coarse taxol product separating and purifying process |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN1244568C (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1331859C (en) * | 2005-01-04 | 2007-08-15 | 四川华申科技开发有限公司 | Separation of taxinol from cephalotaxin |
CN101177421B (en) * | 2006-11-07 | 2010-12-15 | 上海天伟生物制药有限公司 | Method for preparing high-purity taxone compounds |
CN102260227A (en) * | 2011-06-21 | 2011-11-30 | 沈阳化工大学 | Method for separating paclitaxel and related taxane substances |
CN112521349A (en) * | 2020-11-11 | 2021-03-19 | 福建齐衡科技有限公司 | Method for purifying paclitaxel |
-
2003
- 2003-09-22 CN CN 03135916 patent/CN1244568C/en not_active Expired - Fee Related
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1331859C (en) * | 2005-01-04 | 2007-08-15 | 四川华申科技开发有限公司 | Separation of taxinol from cephalotaxin |
CN101177421B (en) * | 2006-11-07 | 2010-12-15 | 上海天伟生物制药有限公司 | Method for preparing high-purity taxone compounds |
CN102260227A (en) * | 2011-06-21 | 2011-11-30 | 沈阳化工大学 | Method for separating paclitaxel and related taxane substances |
CN102260227B (en) * | 2011-06-21 | 2013-10-30 | 沈阳化工大学 | Method for separating paclitaxel and related taxane substances |
CN112521349A (en) * | 2020-11-11 | 2021-03-19 | 福建齐衡科技有限公司 | Method for purifying paclitaxel |
CN112521349B (en) * | 2020-11-11 | 2023-04-07 | 福建齐衡科技有限公司 | Method for purifying paclitaxel |
Also Published As
Publication number | Publication date |
---|---|
CN1244568C (en) | 2006-03-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN100343205C (en) | Method for separating Chinese medicinal active substances | |
CN1160345C (en) | Method for high yield extraction of paclitaxel from paclitaxel-containing material | |
CN1923829A (en) | Preparation method and use of separating and purifying lotus leaf flavone and lotus leaf alkaloid by employing polyamide | |
CN1107150A (en) | Method of using ion exchange media to increase taxane yields | |
CN1166780C (en) | Method for mass production of taxol from taxus genus plant | |
CN1244568C (en) | Coarse taxol product separating and purifying process | |
CN1570133A (en) | Ginsenoside Compound-K preparing method | |
KR100816491B1 (en) | Method for separation and purification of 13-dehydroxybaccatin iii and 10-deacetylpaclitaxel from taxans-containing materials | |
CN1172664C (en) | Agent for lowering prolactin | |
CN1392135A (en) | Process for enriching and purifying capsaicin with macroporous adsorption resin | |
CN1247510C (en) | Method for separating 6-gingerol from ginger | |
CN103145722B (en) | A kind of method of high speed adverse current chromatogram separating-purifying ebormycine | |
CN102311413A (en) | Method for extracting moracin A from cortex mori | |
CN1164599C (en) | Process for preparing total alkaloid of siberian fritillary bulb with antitussive and phlegm-eliminating action | |
CN1246316C (en) | Method for separating major monomeric compoent of soybean isoflavone | |
CN1298712C (en) | Method for elementary separating 10-noracetyl Baccatins III from branches and leaves of yew | |
CN101045718A (en) | Method for separating and purifying 10-deacetyl Baccatins III | |
US20070190623A1 (en) | Process for purification and recovery of paclitaxel compounds | |
CN101033218A (en) | Method of extracting Paclitaxel and 9-dihydro-13-acetyl baccatin III from taxus genus | |
CN1202099C (en) | Method for extracting and purifying 10-desacetyl bakading III (10-DABIII) | |
CN1627942A (en) | Process for isolating srtemisinin from artemisia annua | |
CN1680290A (en) | Oximated ginger phenol and its synthesis and use | |
CN106084251B (en) | The separation of humic acid, fractional extraction method in a kind of aerosol | |
CN103242268A (en) | Method for initially separating 10-deacetyl baccatin III from yew branches/leaves | |
CN102190665A (en) | Method for separating and purifying artemisinin by activated charcoal column chromatography employing nonaqueous system |
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 | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20060308 |
|
CF01 | Termination of patent right due to non-payment of annual fee |