CN102464699A - A kind of preparation method of sodium carbenate - Google Patents
A kind of preparation method of sodium carbenate Download PDFInfo
- Publication number
- CN102464699A CN102464699A CN2010105516259A CN201010551625A CN102464699A CN 102464699 A CN102464699 A CN 102464699A CN 2010105516259 A CN2010105516259 A CN 2010105516259A CN 201010551625 A CN201010551625 A CN 201010551625A CN 102464699 A CN102464699 A CN 102464699A
- Authority
- CN
- China
- Prior art keywords
- carbenoxolone
- glycyrrhetinic acid
- reaction medium
- reaction
- preparation
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 title abstract 4
- 229910052708 sodium Inorganic materials 0.000 title abstract 4
- 239000011734 sodium Substances 0.000 title abstract 4
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 claims abstract description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 16
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229960003720 enoxolone Drugs 0.000 claims abstract description 16
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000012429 reaction media Substances 0.000 claims abstract description 10
- 239000000376 reactant Substances 0.000 claims abstract description 4
- OBZHEBDUNPOCJG-SZTGPWMUSA-N carbenoxolone Chemical compound C([C@H]1C2=CC(=O)[C@@H]34)[C@](C)(C(O)=O)CC[C@@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@H]1[C@@]3(C)CC[C@@H](OC(=O)CCC(O)=O)C1(C)C OBZHEBDUNPOCJG-SZTGPWMUSA-N 0.000 claims description 29
- 229960000530 carbenoxolone Drugs 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000005886 esterification reaction Methods 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 238000005507 spraying Methods 0.000 claims description 3
- 230000003113 alkalizing effect Effects 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 8
- 239000000047 product Substances 0.000 abstract description 7
- 239000012043 crude product Substances 0.000 abstract description 3
- 239000003513 alkali Substances 0.000 abstract description 2
- 239000012535 impurity Substances 0.000 abstract description 2
- 230000035484 reaction time Effects 0.000 abstract description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 abstract 1
- 239000007809 chemical reaction catalyst Substances 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 229940014800 succinic anhydride Drugs 0.000 abstract 1
- -1 succinic anhydride compound Chemical class 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 230000002467 anti-pepsin effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 125000002168 glycyrrhetinic acid group Chemical group 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 229940030188 solu-delta-cortef Drugs 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical compound O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 208000012991 uterine carcinoma Diseases 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种甘珀酸钠的制备方法。本发明采用甘草次酸和丁二酸酐化合物作为反应物，使用1，1-二氯乙烷或氯仿作为反应介质，使用三乙胺或4-二甲氨基吡啶作为反应催化剂，得到的粗产物通过重结晶，加碱、水调整溶液为弱碱性将杂质与甘珀酸钠分离。本发明使用反应介质少，纯化过程中使用水，反应时间短，产物甘珀酸钠纯度＞97％。The invention discloses a preparation method of sodium carbenate. The present invention adopts glycyrrhetinic acid and succinic anhydride compound as reactant, uses 1,1-dichloroethane or chloroform as reaction medium, uses triethylamine or 4-dimethylaminopyridine as reaction catalyst, and the crude product that obtains passes through Recrystallize, add alkali and water to adjust the solution to be weakly alkaline, and separate impurities from sodium carbenoxetate. The invention uses less reaction medium, uses water in the purification process, has short reaction time, and the purity of the product sodium carbenate is more than 97%.
Description
Technical field
The present invention relates to a kind of to the method for preparing Carbenoxolone by glycyrrhetinic acid.
Background technology
Carbenoxolone is glycyrrhetinic acid and succinyl oxide esterification reaction product, is stomach ulcer, duodenal ulcer and stomatocace medication preferably.
Carbenoxolone is the mucus secretion that can increase stomach mucous membrane at the mechanism of action of stomach; Reduce coming off of gastric epithelial cell, can in gastric mucosal cell, suppress propepsin, in stomach, can combine with stomach en-; The vigor of inhibitory enzyme about 50%; Thereby the protection ulcer surface promotes tissue regeneration and healing, and is the most suitable to unsuitable operator.Recently research shows that Carbenoxolone has curative effect preferably to uterus carcinoma, the rectum cancer, mammary cancer and bladder cancer etc., and effect surpasses cancer therapy drugs such as methotrexate, vincristine(VCR), and toxic side effect is little.Carbenoxolone is included in Chinese Pharmacopoeia in 1985 as efficient anti-peptic ulcer class medicine the earliest.
Since the sixties in 20th century, synthetic Carbenoxolone was used to treat ulcer, considerably less to the study on the synthesis document of Carbenoxolone both at home and abroad from Siegfried Gottfried etc., also do not see domestic patent report.The siegfried that traces it to its cause uses pyridine both as reaction solvent, again as the Preparation of Catalyst Carbenoxolone, good productive rate and product yield is arranged.But be to use pyridine also to have many weak points as reaction solvent, the pyridine increase production cost that costs an arm and a leg, pyridine are corrosive high to the production unit requirement.Even the improved preparation method of other scholars also just substituted pyridine with chloroform afterwards, catalyzer becomes triethylamine, and reaction still need be carried out more than 20 hours.Also only be applicable to the prepared in laboratory Carbenoxolone but improve one's methods, because the toxicity of chloroform makes it be not suitable for suitability for industrialized production.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of Carbenoxolone.
The present invention realizes through following measure:
The present invention adopts glycyrrhetinic acid and Succinic anhydried compound as reactant; Use 1; 1-ethylene dichloride or chloroform are as reaction medium (solvent); Use triethylamine or 4-Dimethylamino pyridine as catalysts, the crude product that obtains is through recrystallization, adds alkali, water adjustment solution is that weakly alkaline is separated impurity with Carbenoxolone.
A kind of preparation method of Carbenoxolone; It is characterized in that this method adopts glycyrrhetinic acid and Succinic anhydried compound as reactant, triethylamine or 4-Dimethylamino pyridine be as catalyzer, and 1; 1-ethylene dichloride or chloroform are reaction medium; Carrying out the reflux esterification after 12-18 hour, steam reaction medium and obtain the carbenoxolone bullion, is that purified reagent is carried out recrystallization with the aqueous solution; Use aqueous sodium hydroxide solution to be alkalizing agent adjustment pH value of solution value to 7～8, extract with spray-dryer and obtain Carbenoxolone.
Spraying drying EAT of the present invention is 180～200 ℃, and input speed is 30～50 ml/min.
Reaction medium of the present invention (solvent) consumption is 6-10 a times of glycyrrhetinic acid weight.
Catalyst levels of the present invention is 0.01-0.2 a times of glycyrrhetinic acid weight.
The add-on of Succinic anhydried of the present invention is 0.21-0.42 a times of glycyrrhetinic acid weight.
The present invention uses reaction medium few, makes water in the purge process, and the reaction times is short, product Carbenoxolone purity＞97%.
The present invention compares with the traditional preparation process method, and water uses spray-dryer to produce product as the Carbenoxolone purified reagent in Carbenoxolone preparation, purifies and produces process and also can use acetone, Virahol equal solvent.Carbenoxolone preparation technology is improved and simplifies, and preparation efficiency is improved, and the product postprocessing device is oversimplified, and reduces the solvent usage quantity, and this method prepares Carbenoxolone and do not see bibliographical information as yet.
The present invention is in the product postprocessing process, and dried Meticortene Solu-Delta-cortef extracts and uses spray-drying process, does not use organic solvents such as ethanol, has reduced production cost.
The present invention has following substantial advantage: the carbenoxolone purge process is a water, not with an organic solvent.Carbenoxolone is dissolved in and is prepared into Carbenoxolone in the buck.Carbenoxolone solution uses spraying drying to extract the Carbenoxolone solid.
Embodiment
Embodiment 1
The glycyrrhetinic acid that in reaction vessel, adds 300 grams adds 1 of 180 grams, the 1-ethylene dichloride, and Succinic anhydried 63 grams, catalyzer 4-Dimethylamino pyridine 3 grams, the intensification stirring reaction, when temperature to 65 in the reaction vessel ℃, continuous backflow reaction 12 hours.
Steam in the reaction vessel 1, the 1-ethylene dichloride, solid crude product is dissolved in the 2400 gram water of heat, heat filtering; The filtrating cooled and filtered is received solid product, and product adds 5000 gram water, 50 gram sodium hydroxide, dissolves after 0.5 hour, filters; Filtrating adjustment pH=7～8, it is 180～200 ℃ that spray-dryer is set EAT, input speed is 30～50 ml/min; Make filtrating get into spray-dryer with peristaltic pump, collecting 247.3 gram solid matters is Carbenoxolone, and purity is 97.2%.
Embodiment 2
Reaction adds the glycyrrhetinic acid of 300 grams with embodiment 1 in reaction vessel, add the chloroform of 1800 grams; Succinic anhydried 63 grams, catalyzer 4-Dimethylamino pyridine 3 grams, intensification stirring reaction; When temperature to 65 in the reaction vessel ℃; Continuous backflow reaction 12 hours obtains 247.3 gram Carbenoxolones, and purity is 97.2%.
Embodiment 3
Reaction adds the glycyrrhetinic acid of 300 grams with embodiment 1 in reaction vessel, add 1 of 1800 grams; The 1-ethylene dichloride, Succinic anhydried 63 grams, catalyst of triethylamine 30 grams; The intensification stirring reaction, when temperature to 65 in the reaction vessel ℃, continuous backflow reaction 12 hours; Obtain 245.3 gram Carbenoxolones, purity is 97.5%.
Embodiment 4
Reaction adds the glycyrrhetinic acid of 300 grams with embodiment 1 in reaction vessel, add the chloroform of 1800 grams; Succinic anhydried 63 grams, catalyst of triethylamine 30 grams, intensification stirring reaction; When temperature to 65 in the reaction vessel ℃; Continuous backflow reaction 12 hours obtains 245.3 gram Carbenoxolones, and purity is 97.5%.
Claims (5)
1. the preparation method of a Carbenoxolone; It is characterized in that this method adopts glycyrrhetinic acid and Succinic anhydried compound as reactant, triethylamine or 4-Dimethylamino pyridine be as catalyzer, and 1; 1-ethylene dichloride or chloroform are reaction medium; Carrying out the reflux esterification after 12-18 hour, steam reaction medium and obtain the carbenoxolone bullion, is that purified reagent is carried out recrystallization with the aqueous solution; Use aqueous sodium hydroxide solution to be alkalizing agent adjustment pH value of solution value to 7～8, extract with spray-dryer and obtain Carbenoxolone.
2. the method for claim 1 is characterized in that the spraying drying EAT is 180～200 ℃, and input speed is 30～50 ml/min.
3. the method for claim 1 is characterized in that the reaction medium consumption is 6-10 a times of glycyrrhetinic acid weight.
4. the method for claim 1 is characterized in that catalyst levels is 0.01-0.2 a times of glycyrrhetinic acid weight.
5. the method for claim 1, the add-on that it is characterized in that Succinic anhydried be glycyrrhetinic acid weight 0.21-0.42 doubly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105516259A CN102464699A (en) | 2010-11-16 | 2010-11-16 | A kind of preparation method of sodium carbenate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105516259A CN102464699A (en) | 2010-11-16 | 2010-11-16 | A kind of preparation method of sodium carbenate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102464699A true CN102464699A (en) | 2012-05-23 |
Family
ID=46068857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010105516259A Pending CN102464699A (en) | 2010-11-16 | 2010-11-16 | A kind of preparation method of sodium carbenate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102464699A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749481A (en) * | 2015-11-20 | 2017-05-31 | 刘力 | Enoxolone class noval chemical compound entity and application thereof |
| US9939076B2 (en) | 2012-11-19 | 2018-04-10 | Flowserve Management Company | Control systems for valve actuators, valve actuators and related methods |
| CN108186652A (en) * | 2017-12-28 | 2018-06-22 | 深圳大学 | Gap connects iuntercellular communication inhibitor 18-BETA-Glycyrrhetinic acid and is preparing the application in preventing and treating hepatocellular carcinoma drug |
| CN117924403A (en) * | 2024-01-12 | 2024-04-26 | 王叔和生物医药(武汉)有限公司 | Preparation method of sodium carbenoxolone |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101200488A (en) * | 2007-12-07 | 2008-06-18 | 北京润德康医药技术有限公司 | Novel biogastrone acid derivatives, preparation method and medical uses thereof |
| CN101230083A (en) * | 2008-01-09 | 2008-07-30 | 北京润德康医药技术有限公司 | Novel glycyrrhetinic acid derivatives and preparation method thereof |
| CN101642573A (en) * | 2009-08-25 | 2010-02-10 | 南开大学 | Chitosan-based hepatic-targeted nano-particle drug delivery system and preparation method thereof |
-
2010
- 2010-11-16 CN CN2010105516259A patent/CN102464699A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101200488A (en) * | 2007-12-07 | 2008-06-18 | 北京润德康医药技术有限公司 | Novel biogastrone acid derivatives, preparation method and medical uses thereof |
| CN101230083A (en) * | 2008-01-09 | 2008-07-30 | 北京润德康医药技术有限公司 | Novel glycyrrhetinic acid derivatives and preparation method thereof |
| CN101642573A (en) * | 2009-08-25 | 2010-02-10 | 南开大学 | Chitosan-based hepatic-targeted nano-particle drug delivery system and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| LI HUANG等: "Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9939076B2 (en) | 2012-11-19 | 2018-04-10 | Flowserve Management Company | Control systems for valve actuators, valve actuators and related methods |
| CN106749481A (en) * | 2015-11-20 | 2017-05-31 | 刘力 | Enoxolone class noval chemical compound entity and application thereof |
| CN108186652A (en) * | 2017-12-28 | 2018-06-22 | 深圳大学 | Gap connects iuntercellular communication inhibitor 18-BETA-Glycyrrhetinic acid and is preparing the application in preventing and treating hepatocellular carcinoma drug |
| CN117924403A (en) * | 2024-01-12 | 2024-04-26 | 王叔和生物医药(武汉)有限公司 | Preparation method of sodium carbenoxolone |
| CN117924403B (en) * | 2024-01-12 | 2024-09-20 | 王叔和生物医药(武汉)有限公司 | Preparation method of sodium carbenoxolone |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103073438B (en) | Ambroxol hydrochloride compound refining method | |
| CN104974060A (en) | Method for preparing sodium, 8-(2-hydroxybenzamido)octanoate | |
| CN106256824B (en) | Preparation method of high-purity delafloxacin meglumine salt | |
| CN106892950B (en) | Preparation method of high-content troxerutin | |
| CN105218621B (en) | Dehydroabietic acid benzimidazole Schiff base heterocyclic derivatives with anti-tumor activity and preparation method therefor and application thereof | |
| CN102464699A (en) | A kind of preparation method of sodium carbenate | |
| CN102060860A (en) | Preparation method of Marbofloxacin | |
| CN102786431A (en) | Preparation method of propacetamol hydrochloride | |
| CN102452972B (en) | Method for preparing oxiracetam compound | |
| CN108912004A (en) | A kind of synthetic method of pregabalin intermediate | |
| CN104974057B (en) | The preparation method and important intermediate of a kind of bromfenac sodium | |
| CN100537552C (en) | A kind of method for preparing repaglinide | |
| CN102417472A (en) | Preparation method of florfenicol | |
| CN102491953A (en) | Method for synthesizing florfenicol midbody RT0131 | |
| CN108569975A (en) | A kind of preparation method of bromfenac sodium times semihydrate | |
| CN103113294A (en) | Synthesizing method of rebamipide | |
| CN103880776B (en) | A kind of method preparing 2-amino-5-alkyl-1,3,4-thiadiazoles | |
| CN102199103B (en) | Improved method for synthesizing L-thyroxine sodium | |
| CN102030715B (en) | Method for synthesizing cytosine | |
| CN101445530A (en) | Method for preparing high-bioavailability derivatives of hesperidin | |
| CN102180864A (en) | Preparation method of strontium ranelate | |
| CN108997165B (en) | Method for synthesizing balsalazide disodium | |
| CN103772479B (en) | A kind of method that TANSHINONES crude extract prepares sodium tanshinone IIA sulfate | |
| CN112694436A (en) | Method for synthesizing arecoline | |
| CN104292133A (en) | Method for synthesizing anti-cancer drug vorinostat |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120523 |