CN104031105B - 一种胞磷胆碱钠的制备方法 - Google Patents
一种胞磷胆碱钠的制备方法 Download PDFInfo
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- CN104031105B CN104031105B CN201410250694.4A CN201410250694A CN104031105B CN 104031105 B CN104031105 B CN 104031105B CN 201410250694 A CN201410250694 A CN 201410250694A CN 104031105 B CN104031105 B CN 104031105B
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- 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 32
- 229960004774 citicoline sodium Drugs 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 6
- 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 abstract description 5
- 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 abstract description 4
- 235000006408 oxalic acid Nutrition 0.000 claims abstract description 4
- 239000002244 precipitate Substances 0.000 claims abstract description 4
- 238000001953 recrystallisation Methods 0.000 claims abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 32
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 15
- 239000000047 product Substances 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 13
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 10
- 239000000706 filtrate Substances 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- ICVPTJCCKTXCDT-UHFFFAOYSA-L calcium;2-(trimethylazaniumyl)ethyl phosphate;chloride Chemical compound [Cl-].[Ca+2].C[N+](C)(C)CCOP([O-])([O-])=O ICVPTJCCKTXCDT-UHFFFAOYSA-L 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 238000001556 precipitation Methods 0.000 claims description 4
- 229930183912 Cytidylic acid Natural products 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 239000006227 byproduct Substances 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 230000008030 elimination Effects 0.000 claims description 2
- 238000003379 elimination reaction Methods 0.000 claims description 2
- 238000007670 refining Methods 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract 1
- 239000011575 calcium Substances 0.000 abstract 1
- 229910052791 calcium Inorganic materials 0.000 abstract 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 4
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- 229960004756 ethanol Drugs 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
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- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 description 2
- 229950004354 phosphorylcholine Drugs 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 description 1
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- 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
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- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 208000031650 Surgical Wound Infection Diseases 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
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- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
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- 230000003570 biosynthesizing effect Effects 0.000 description 1
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- 208000029028 brain injury Diseases 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000003727 cerebral blood flow Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229960001284 citicoline Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
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- 150000003904 phospholipids Chemical class 0.000 description 1
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- 229920001184 polypeptide Polymers 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
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- 102000004196 processed proteins & peptides Human genes 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
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CN201410250694.4A CN104031105B (zh) | 2014-06-06 | 2014-06-06 | 一种胞磷胆碱钠的制备方法 |
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CN201410250694.4A CN104031105B (zh) | 2014-06-06 | 2014-06-06 | 一种胞磷胆碱钠的制备方法 |
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CN104031105A CN104031105A (zh) | 2014-09-10 |
CN104031105B true CN104031105B (zh) | 2015-07-15 |
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Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
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CN105693798A (zh) * | 2016-03-18 | 2016-06-22 | 新乡学院 | 一种胞二磷胆碱及不使用氯化磷酸胆碱钙的胞二磷胆碱的合成方法 |
CN106146590A (zh) * | 2016-06-29 | 2016-11-23 | 陈建峰 | 一种胞磷胆碱钠的制备方法 |
CN109160932A (zh) * | 2017-08-18 | 2019-01-08 | 刘兆娟 | 一种11/2水胞磷胆碱钠化合物及其药物组合物制剂 |
CN111574576B (zh) * | 2020-05-13 | 2021-07-06 | 广东先强药业有限公司 | 一种地夸磷索钠的精制方法 |
CN114057813B (zh) * | 2021-11-30 | 2023-06-02 | 新乡拓新药业股份有限公司 | 一种合成胞二磷胆碱钠的方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN1944661A (zh) * | 2006-09-28 | 2007-04-11 | 苏州天马医药集团天吉生物制药有限公司 | 胞磷胆碱钠的制备方法 |
WO2013128393A1 (en) * | 2012-02-28 | 2013-09-06 | Frichem Private Limited | A process for preparing pure citicoline (cdp-choline) |
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2014
- 2014-06-06 CN CN201410250694.4A patent/CN104031105B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN1944661A (zh) * | 2006-09-28 | 2007-04-11 | 苏州天马医药集团天吉生物制药有限公司 | 胞磷胆碱钠的制备方法 |
WO2013128393A1 (en) * | 2012-02-28 | 2013-09-06 | Frichem Private Limited | A process for preparing pure citicoline (cdp-choline) |
Non-Patent Citations (1)
Title |
---|
胞二磷胆碱的生产;顾复昌等;《发酵科技通讯》;20070131;第36卷(第1期);第4.2部分 * |
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Address after: 331800 No. 6, Dongshan Industrial Park, Dongxiang Economic Development Zone, Fuzhou, Jiangxi. Patentee after: HUIYINBI GROUP JIANGXI EAST ASIA PHARMACEUTICAL Co.,Ltd. Address before: 331800 No. 6, Dongshan Industrial Park, Dongxiang County Economic Development Zone, Jiangxi, Fuzhou, Jiangxi Patentee before: HUIYINBI GROUP (JIANGXI) EAST ASIA PHARMACEUTICAL CO.,LTD. |
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Effective date of registration: 20191227 Address after: 246600 Changning Industrial Zone, Yuexi County, Anqing, Anhui Patentee after: Anqing Huiyinbi Pharmaceutical Co.,Ltd. Address before: 331800 No. 6, Dongshan Industrial Park, Dongxiang Economic Development Zone, Fuzhou, Jiangxi. Patentee before: HUIYINBI GROUP JIANGXI EAST ASIA PHARMACEUTICAL Co.,Ltd. |
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Effective date of registration: 20240308 Address after: 331800 No. 6, Dongshan Industrial Park, Dongxiang Economic Development Zone, Fuzhou, Jiangxi. Patentee after: HUIYINBI GROUP JIANGXI EAST ASIA PHARMACEUTICAL Co.,Ltd. Country or region after: China Address before: 246600 Changning Industrial Zone, Yuexi County, Anqing City, Anhui Province Patentee before: Anqing Huiyinbi Pharmaceutical Co.,Ltd. Country or region before: China |