CN1944661A - Process for preparing citicoline sodium - Google Patents
Process for preparing citicoline sodium Download PDFInfo
- Publication number
- CN1944661A CN1944661A CN 200610096512 CN200610096512A CN1944661A CN 1944661 A CN1944661 A CN 1944661A CN 200610096512 CN200610096512 CN 200610096512 CN 200610096512 A CN200610096512 A CN 200610096512A CN 1944661 A CN1944661 A CN 1944661A
- Authority
- CN
- China
- Prior art keywords
- citicoline sodium
- preparation
- consumption
- liquid
- yeast
- 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
- YWAFNFGRBBBSPD-OCMLZEEQSA-M sodium;[[(2r,3s,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound [Na+].O[C@@H]1[C@H](O)[C@@H](COP([O-])(=O)OP([O-])(=O)OCC[N+](C)(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 YWAFNFGRBBBSPD-OCMLZEEQSA-M 0.000 title claims abstract description 45
- 229960004774 citicoline sodium Drugs 0.000 title claims abstract description 44
- 238000004519 manufacturing process Methods 0.000 title description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 36
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 33
- 238000000926 separation method Methods 0.000 claims abstract description 26
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims abstract description 25
- 238000002360 preparation method Methods 0.000 claims abstract description 23
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 15
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 claims abstract description 12
- 229950004354 phosphorylcholine Drugs 0.000 claims abstract description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 11
- 239000008103 glucose Substances 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 9
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims abstract description 5
- 239000000047 product Substances 0.000 claims description 38
- 239000007787 solid Substances 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 239000000243 solution Substances 0.000 claims description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- IERHLVCPSMICTF-XVFCMESISA-N cytidine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 IERHLVCPSMICTF-XVFCMESISA-N 0.000 claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000012043 crude product Substances 0.000 claims description 12
- 238000002425 crystallisation Methods 0.000 claims description 12
- 230000008025 crystallization Effects 0.000 claims description 12
- 239000003513 alkali Substances 0.000 claims description 11
- 230000001476 alcoholic effect Effects 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 238000001179 sorption measurement Methods 0.000 claims description 7
- 101800000263 Acidic protein Proteins 0.000 claims description 6
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 claims description 6
- 238000003916 acid precipitation Methods 0.000 claims description 6
- 230000009849 deactivation Effects 0.000 claims description 6
- 238000010612 desalination reaction Methods 0.000 claims description 6
- 238000001471 micro-filtration Methods 0.000 claims description 6
- 102000039446 nucleic acids Human genes 0.000 claims description 6
- 108020004707 nucleic acids Proteins 0.000 claims description 6
- 150000007523 nucleic acids Chemical class 0.000 claims description 6
- 239000013049 sediment Substances 0.000 claims description 6
- 238000000108 ultra-filtration Methods 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- 230000003570 biosynthesizing effect Effects 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 229930183912 Cytidylic acid Natural products 0.000 claims description 3
- IERHLVCPSMICTF-UHFFFAOYSA-N cytidine monophosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(O)=O)O1 IERHLVCPSMICTF-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 230000008014 freezing Effects 0.000 claims 1
- 238000007710 freezing Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 7
- 102000004190 Enzymes Human genes 0.000 abstract description 6
- 108090000790 Enzymes Proteins 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 3
- 238000000605 extraction Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract 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 abstract description 2
- 230000036983 biotransformation Effects 0.000 abstract description 2
- 238000005516 engineering process Methods 0.000 abstract description 2
- 239000003456 ion exchange resin Substances 0.000 abstract description 2
- 229920003303 ion-exchange polymer Polymers 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 239000011942 biocatalyst Substances 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- NJNWCIAPVGRBHO-UHFFFAOYSA-N 2-hydroxyethyl-dimethyl-[(oxo-$l^{5}-phosphanylidyne)methyl]azanium Chemical class OCC[N+](C)(C)C#P=O NJNWCIAPVGRBHO-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 230000006920 protein precipitation Effects 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- ZWIADYZPOWUWEW-XVFCMESISA-N CDP Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O1 ZWIADYZPOWUWEW-XVFCMESISA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229960001284 citicoline Drugs 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- PCDQPRRSZKQHHS-CCXZUQQUSA-N Cytarabine Triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-CCXZUQQUSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000000274 adsorptive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- -1 choline Cytidine diphosphate ester Chemical class 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
Claims (8)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2006100965128A CN100564537C (en) | 2006-09-28 | 2006-09-28 | The preparation method of CITICOLINE SODIUM |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2006100965128A CN100564537C (en) | 2006-09-28 | 2006-09-28 | The preparation method of CITICOLINE SODIUM |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1944661A true CN1944661A (en) | 2007-04-11 |
CN100564537C CN100564537C (en) | 2009-12-02 |
Family
ID=38044311
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB2006100965128A Active CN100564537C (en) | 2006-09-28 | 2006-09-28 | The preparation method of CITICOLINE SODIUM |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN100564537C (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102010454A (en) * | 2010-12-02 | 2011-04-13 | 胡建荣 | Citicoline sodium compound and new method thereof |
CN103509074A (en) * | 2013-10-10 | 2014-01-15 | 江西科技师范大学 | Synthesis method of nucleoside diphosphate 6-deoxy-L-pyranose |
CN103509073A (en) * | 2013-08-29 | 2014-01-15 | 洪军 | Citicoline sodium compound |
CN103849666A (en) * | 2013-05-08 | 2014-06-11 | 开平牵牛生化制药有限公司 | Method for catalytically producing citicoline sodium with immobilized enzyme |
CN104031105A (en) * | 2014-06-06 | 2014-09-10 | 浙江天冉药物研究有限公司 | Method for preparing citicoline sodium |
CN104592335A (en) * | 2014-12-24 | 2015-05-06 | 江西科技师范大学 | Method for synthesizing nucleoside diphosphonic acid choline sodium salts |
CN105732752A (en) * | 2016-03-18 | 2016-07-06 | 新乡学院 | Citicoline and synthetic method thereof |
CN106146590A (en) * | 2016-06-29 | 2016-11-23 | 陈建峰 | A kind of preparation method of C14H25N4NaO11P2 |
CN109836468A (en) * | 2017-11-24 | 2019-06-04 | 苏州华赛生物工程技术有限公司 | A method of the purifying citicoline sodium from microbial fermentation solution |
CN113769794A (en) * | 2021-07-06 | 2021-12-10 | 沁浩膜技术(厦门)有限公司 | Ion exchange system and method for continuously removing impurities in citicoline sodium |
-
2006
- 2006-09-28 CN CNB2006100965128A patent/CN100564537C/en active Active
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102010454B (en) * | 2010-12-02 | 2012-03-07 | 胡建荣 | Citicoline sodium compound and new method thereof |
CN102010454A (en) * | 2010-12-02 | 2011-04-13 | 胡建荣 | Citicoline sodium compound and new method thereof |
CN103849666A (en) * | 2013-05-08 | 2014-06-11 | 开平牵牛生化制药有限公司 | Method for catalytically producing citicoline sodium with immobilized enzyme |
CN103849666B (en) * | 2013-05-08 | 2015-09-02 | 开平牵牛生化制药有限公司 | A kind of method of immobilized enzyme catalysis production CITICOLINE SODIUM |
CN103509073B (en) * | 2013-08-29 | 2016-01-06 | 洪军 | A kind of Citicoline sodium compound |
CN103509073A (en) * | 2013-08-29 | 2014-01-15 | 洪军 | Citicoline sodium compound |
CN103509074A (en) * | 2013-10-10 | 2014-01-15 | 江西科技师范大学 | Synthesis method of nucleoside diphosphate 6-deoxy-L-pyranose |
CN104031105A (en) * | 2014-06-06 | 2014-09-10 | 浙江天冉药物研究有限公司 | Method for preparing citicoline sodium |
CN104031105B (en) * | 2014-06-06 | 2015-07-15 | 回音必集团(江西)东亚制药有限公司 | Method for preparing citicoline sodium |
CN104592335A (en) * | 2014-12-24 | 2015-05-06 | 江西科技师范大学 | Method for synthesizing nucleoside diphosphonic acid choline sodium salts |
CN105732752A (en) * | 2016-03-18 | 2016-07-06 | 新乡学院 | Citicoline and synthetic method thereof |
CN106146590A (en) * | 2016-06-29 | 2016-11-23 | 陈建峰 | A kind of preparation method of C14H25N4NaO11P2 |
CN109836468A (en) * | 2017-11-24 | 2019-06-04 | 苏州华赛生物工程技术有限公司 | A method of the purifying citicoline sodium from microbial fermentation solution |
CN113769794A (en) * | 2021-07-06 | 2021-12-10 | 沁浩膜技术(厦门)有限公司 | Ion exchange system and method for continuously removing impurities in citicoline sodium |
CN113769794B (en) * | 2021-07-06 | 2024-04-05 | 沁浩膜技术(厦门)有限公司 | Ion exchange system and method for continuously removing impurities in citicoline sodium |
Also Published As
Publication number | Publication date |
---|---|
CN100564537C (en) | 2009-12-02 |
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Legal Events
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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: SUZHOU TIANMA SPECIALTY CHEMICAL CO., LTD. Free format text: FORMER OWNER: TIANJI BIOLOGICAL PHARMACEUTICAL CO., LTD., SUZHOU TIANMA MEDICINE GROUP Effective date: 20140604 |
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C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20140604 Address after: Town of Wuzhong District road Suzhou city Jiangsu province 215101 No. 199-1 Patentee after: Suzhou Tianma Fine Chemical Product Co., Ltd. Address before: Mudu Garden Road Suzhou city Jiangsu province 215101 No. 199 Patentee before: Suzhou Tianma Group Tianji Bio-Pharmaceutical Co.,Ltd. |
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TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20180807 Address after: No. 122, Hu Guan Zhen Lu Qing Road, Suzhou, Jiangsu, Jiangsu Patentee after: Suzhou Tianma Pharmaceutical Co., Ltd. Address before: 215101 Huayuan East Road, Mu Du Town, Wuzhong District, Suzhou, Jiangsu 199-1 Patentee before: Suzhou Tianma Fine Chemical Product Co., Ltd. |
|
CP01 | Change in the name or title of a patent holder |
Address after: Suzhou City, Jiangsu province 215000 Guan Hu Zhen Hu Qing Road No. 122 Patentee after: Suzhou Zhengji Pharmaceutical Co.,Ltd. Address before: Suzhou City, Jiangsu province 215000 Guan Hu Zhen Hu Qing Road No. 122 Patentee before: SUZHOU TIANMA PHARMACEUTICAL Co.,Ltd. |
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CP01 | Change in the name or title of a patent holder |