CN101538300A - 一种胞二磷胆碱的盐析-溶析结晶方法 - Google Patents
一种胞二磷胆碱的盐析-溶析结晶方法 Download PDFInfo
- Publication number
- CN101538300A CN101538300A CN200810019855A CN200810019855A CN101538300A CN 101538300 A CN101538300 A CN 101538300A CN 200810019855 A CN200810019855 A CN 200810019855A CN 200810019855 A CN200810019855 A CN 200810019855A CN 101538300 A CN101538300 A CN 101538300A
- Authority
- CN
- China
- Prior art keywords
- cytidine diphosphate
- citicoline
- crystallization
- sodium
- crystallization method
- 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
- 238000002425 crystallisation Methods 0.000 title claims abstract description 42
- 229960001284 citicoline Drugs 0.000 title abstract 6
- 238000005185 salting out Methods 0.000 title abstract 2
- RZZPDXZPRHQOCG-OJAKKHQRSA-M CDP-choline(1-) Chemical compound 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 RZZPDXZPRHQOCG-OJAKKHQRSA-M 0.000 title 1
- 230000008025 crystallization Effects 0.000 claims abstract description 25
- 239000013078 crystal Substances 0.000 claims abstract description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000007864 aqueous solution Substances 0.000 claims abstract description 14
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 14
- 238000005406 washing Methods 0.000 claims abstract description 8
- 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 claims description 50
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 238000010790 dilution Methods 0.000 claims description 9
- 239000012895 dilution Substances 0.000 claims description 9
- 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 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 8
- 238000000967 suction filtration Methods 0.000 claims description 7
- 238000001291 vacuum drying Methods 0.000 claims description 7
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 229960004249 sodium acetate Drugs 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- 239000004317 sodium nitrate Substances 0.000 claims description 3
- 229940001516 sodium nitrate Drugs 0.000 claims description 3
- 235000010344 sodium nitrate Nutrition 0.000 claims description 3
- 239000001488 sodium phosphate Substances 0.000 claims description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 3
- 235000011152 sodium sulphate Nutrition 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- 229960003339 sodium phosphate Drugs 0.000 claims description 2
- 235000011008 sodium phosphates Nutrition 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 15
- 238000003756 stirring Methods 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 3
- 238000001914 filtration Methods 0.000 abstract description 2
- 239000002245 particle Substances 0.000 abstract description 2
- 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 abstract 5
- 238000001035 drying Methods 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- YCRMVAAMYKKYAU-UHFFFAOYSA-N n-benzyl-4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine Chemical compound N=1C=2CCCCC=2SC=1NCC1=CC=CC=C1 YCRMVAAMYKKYAU-UHFFFAOYSA-N 0.000 abstract 1
- 238000005086 pumping Methods 0.000 abstract 1
- 159000000000 sodium salts Chemical class 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 239000007788 liquid Substances 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- RZZPDXZPRHQOCG-OJAKKHQRSA-O CDP-choline(1+) Chemical compound 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 RZZPDXZPRHQOCG-OJAKKHQRSA-O 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- DJJCXFVJDGTHFX-UHFFFAOYSA-N Uridinemonophosphate Natural products OC1C(O)C(COP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-UHFFFAOYSA-N 0.000 description 1
- FOGRQMPFHUHIGU-UHFFFAOYSA-N Uridylic acid Natural products OC1C(OP(O)(O)=O)C(CO)OC1N1C(=O)NC(=O)C=C1 FOGRQMPFHUHIGU-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000003570 biosynthesizing effect Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003181 encephalopathic effect Effects 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- -1 uridylic acid sodium salt Chemical class 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
Abstract
Description
Claims (7)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008100198553A CN101538300B (zh) | 2008-03-19 | 2008-03-19 | 一种胞二磷胆碱的盐析-溶析结晶方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008100198553A CN101538300B (zh) | 2008-03-19 | 2008-03-19 | 一种胞二磷胆碱的盐析-溶析结晶方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101538300A true CN101538300A (zh) | 2009-09-23 |
CN101538300B CN101538300B (zh) | 2011-11-30 |
Family
ID=41121708
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2008100198553A Active CN101538300B (zh) | 2008-03-19 | 2008-03-19 | 一种胞二磷胆碱的盐析-溶析结晶方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101538300B (zh) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103509073A (zh) * | 2013-08-29 | 2014-01-15 | 洪军 | 一种胞磷胆碱钠化合物 |
WO2018066690A1 (ja) * | 2016-10-06 | 2018-04-12 | 協和発酵バイオ株式会社 | シチジンジリン酸コリンの結晶及びその製造方法 |
CN109836468A (zh) * | 2017-11-24 | 2019-06-04 | 苏州华赛生物工程技术有限公司 | 一种从微生物发酵液中分离纯化胞二磷胆碱钠的方法 |
CN110684066A (zh) * | 2019-05-22 | 2020-01-14 | 广东金城金素制药有限公司 | 胞二磷胆碱药物制剂及其脑梗塞急性期意识障碍的新用途 |
CN111487337A (zh) * | 2020-04-16 | 2020-08-04 | 南通秋之友生物科技有限公司 | 一种胞磷胆碱钠结晶过程的在线控制方法 |
CN115536710A (zh) * | 2022-10-18 | 2022-12-30 | 南京工业大学 | 一种高品质胞苷硫酸盐晶体的制备方法 |
WO2023026449A1 (ja) * | 2021-08-26 | 2023-03-02 | 協和発酵バイオ株式会社 | シチジン-5'-ジリン酸化合物の製造方法 |
RU2800932C2 (ru) * | 2016-10-06 | 2023-08-01 | Киова Хакко Био Ко., Лтд. | Кристалл цитидиндифосфатхолина и способ его получения |
-
2008
- 2008-03-19 CN CN2008100198553A patent/CN101538300B/zh active Active
Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103509073B (zh) * | 2013-08-29 | 2016-01-06 | 洪军 | 一种胞磷胆碱钠化合物 |
CN103509073A (zh) * | 2013-08-29 | 2014-01-15 | 洪军 | 一种胞磷胆碱钠化合物 |
US11186605B2 (en) | 2016-10-06 | 2021-11-30 | Kyowa Hakko Bio Co., Ltd. | Crystal of cytidine diphosphate choline and production method thereof |
WO2018066690A1 (ja) * | 2016-10-06 | 2018-04-12 | 協和発酵バイオ株式会社 | シチジンジリン酸コリンの結晶及びその製造方法 |
CN109790197A (zh) * | 2016-10-06 | 2019-05-21 | 协和发酵生化株式会社 | 胞苷二磷酸胆碱的晶体及其制造方法 |
JPWO2018066690A1 (ja) * | 2016-10-06 | 2019-07-25 | 協和発酵バイオ株式会社 | シチジンジリン酸コリンの結晶及びその製造方法 |
RU2800932C2 (ru) * | 2016-10-06 | 2023-08-01 | Киова Хакко Био Ко., Лтд. | Кристалл цитидиндифосфатхолина и способ его получения |
JP7146640B2 (ja) | 2016-10-06 | 2022-10-04 | 協和発酵バイオ株式会社 | シチジンジリン酸コリンの結晶及びその製造方法 |
AU2017341136B2 (en) * | 2016-10-06 | 2021-07-08 | Kyowa Hakko Bio Co., Ltd. | Crystal of cytidine diphosphate choline and production method thereof |
CN109836468A (zh) * | 2017-11-24 | 2019-06-04 | 苏州华赛生物工程技术有限公司 | 一种从微生物发酵液中分离纯化胞二磷胆碱钠的方法 |
CN110684066A (zh) * | 2019-05-22 | 2020-01-14 | 广东金城金素制药有限公司 | 胞二磷胆碱药物制剂及其脑梗塞急性期意识障碍的新用途 |
CN111487337A (zh) * | 2020-04-16 | 2020-08-04 | 南通秋之友生物科技有限公司 | 一种胞磷胆碱钠结晶过程的在线控制方法 |
WO2023026449A1 (ja) * | 2021-08-26 | 2023-03-02 | 協和発酵バイオ株式会社 | シチジン-5'-ジリン酸化合物の製造方法 |
WO2023027178A1 (ja) * | 2021-08-26 | 2023-03-02 | 協和発酵バイオ株式会社 | シチジン-5'-ジリン酸化合物の製造方法 |
CN115536710A (zh) * | 2022-10-18 | 2022-12-30 | 南京工业大学 | 一种高品质胞苷硫酸盐晶体的制备方法 |
CN115536710B (zh) * | 2022-10-18 | 2024-04-16 | 南京工业大学 | 一种高品质胞苷硫酸盐晶体的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN101538300B (zh) | 2011-11-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101538300B (zh) | 一种胞二磷胆碱的盐析-溶析结晶方法 | |
CN102992957B (zh) | 一种赤藓糖醇的溶析结晶方法 | |
CN100395256C (zh) | 一种5’-核苷一磷酸钠盐的结晶方法 | |
CN103865968B (zh) | 一种提高无水葡萄糖和一水葡萄糖产品品质的工艺 | |
CN102952167A (zh) | 胞苷5’-磷酸二钠的溶析结晶方法 | |
CN101638695B (zh) | 一种结晶果糖的制备方法 | |
CN102924539A (zh) | 一种制备海藻糖晶体的方法 | |
CN103012472B (zh) | 一种磷酸肌酸钠的结晶制备方法 | |
CN103725731A (zh) | 葡萄糖酸钠专用结晶葡萄糖及其制备方法 | |
CN104561195B (zh) | 一种尿苷二磷酸葡萄糖的制备方法 | |
CN1304878A (zh) | 一种复分解法制备硝酸钾的方法 | |
CN104926709A (zh) | 一种l-色氨酸的精制方法 | |
CN103113440B (zh) | 一种硫氰酸红霉素的制备方法 | |
CN113307832A (zh) | 一种制备尿苷酸的方法 | |
CN103060482A (zh) | 玉米淀粉生产结晶果糖的工艺 | |
CN105061289A (zh) | 一种制备药用级l-色氨酸的方法 | |
CN100363376C (zh) | 一种5’-核苷三磷酸钠盐的结晶方法 | |
CN108314696A (zh) | 2-羟基-1,3,5-三-O-苯甲酰基-α-D-呋喃核糖结晶母液的利用方法 | |
CN103664934A (zh) | 一种长春西汀的制备方法 | |
CN110606863B (zh) | 一种n-乙酰神经氨酸二水合物的制备方法 | |
CN114262726A (zh) | 一种利用胞苷酶法合成胞磷胆碱钠的方法 | |
CN102424687A (zh) | 盐酸头孢替安酯的制备方法 | |
CN104894191A (zh) | 一种异麦芽酮糖醇的制备方法 | |
CN110904170A (zh) | 一种f-55果葡糖浆的制备方法 | |
CN103435669A (zh) | 5′-尿苷酸二钠的溶析结晶方法 |
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 | ||
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20160613 Address after: 210032, Jiangsu, Nanjing province hi tech Development Zone, 10 Spark Road, ding industry, A building, 1014 floor, room 10, Nanjing Patentee after: Nanjing Hi Tech Institute of Biotechnology Research Co Ltd Address before: 210009 Nanjing City, Jiangsu Province, the new model road No. 5 Patentee before: Nanjing University of Technology |
|
TR01 | Transfer of patent right |
Effective date of registration: 20210510 Address after: 210000 Room 501, building 5, accelerator phase II, No.11 Yaogu Avenue, Jiangbei new district, Nanjing City, Jiangsu Province Patentee after: Nanjing life original Health Technology Co.,Ltd. Address before: Room 1014, 10 / F, block a, Dingye Baitai biological building, No.10 Xinghuo Road, Nanjing high tech Development Zone, Nanjing, Jiangsu 210032 Patentee before: NANJING INSTITUTE OF WHITE-BIOTECH Co.,Ltd. |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20210609 Address after: 210000 room 206, building 5, accelerator phase II, No.11 Yaogu Avenue, Jiangbei new district, Nanjing City, Jiangsu Province Patentee after: NANJING INSTITUTE OF WHITE-BIOTECH Co.,Ltd. Address before: 210000 Room 501, building 5, accelerator phase II, No.11 Yaogu Avenue, Jiangbei new district, Nanjing City, Jiangsu Province Patentee before: Nanjing life original Health Technology Co.,Ltd. |
|
TR01 | Transfer of patent right |