CN101607955A - 一种低残留硫辛酸的制备方法 - Google Patents
一种低残留硫辛酸的制备方法 Download PDFInfo
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- CN101607955A CN101607955A CNA2008100391404A CN200810039140A CN101607955A CN 101607955 A CN101607955 A CN 101607955A CN A2008100391404 A CNA2008100391404 A CN A2008100391404A CN 200810039140 A CN200810039140 A CN 200810039140A CN 101607955 A CN101607955 A CN 101607955A
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- 235000019136 lipoic acid Nutrition 0.000 title claims abstract description 69
- 229960002663 thioctic acid Drugs 0.000 title claims abstract description 68
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 title 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 claims abstract description 76
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 44
- 238000006243 chemical reaction Methods 0.000 claims abstract description 42
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims abstract description 37
- 239000012043 crude product Substances 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000002253 acid Substances 0.000 claims abstract description 17
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 16
- 238000007127 saponification reaction Methods 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 16
- 238000004073 vulcanization Methods 0.000 claims abstract description 12
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 238000007670 refining Methods 0.000 claims abstract description 8
- 230000020477 pH reduction Effects 0.000 claims abstract description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 64
- 239000011734 sodium Substances 0.000 claims description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 239000005864 Sulphur Substances 0.000 claims description 17
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
- 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 12
- 229910052708 sodium Inorganic materials 0.000 claims description 12
- 238000009156 water cure Methods 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 239000000047 product Substances 0.000 abstract description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 abstract description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 9
- 238000005516 engineering process Methods 0.000 abstract description 6
- 239000006227 byproduct Substances 0.000 abstract description 5
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 abstract description 4
- 238000003912 environmental pollution Methods 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 230000008859 change Effects 0.000 abstract description 2
- 230000028161 membrane depolarization Effects 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 20
- 238000003756 stirring Methods 0.000 description 15
- 239000012065 filter cake Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000013078 crystal Substances 0.000 description 8
- 238000011084 recovery Methods 0.000 description 7
- 239000012153 distilled water Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000010792 warming Methods 0.000 description 6
- 238000010009 beating Methods 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- UUDFBRWLHZIIQX-UHFFFAOYSA-M sodium;5-(dithiolan-3-yl)pentanoate Chemical compound [Na+].[O-]C(=O)CCCCC1CCSS1 UUDFBRWLHZIIQX-UHFFFAOYSA-M 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- 239000003513 alkali Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 229940005605 valeric acid Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- AGBQKNBQESQNJD-ZETCQYMHSA-N (S)-lipoic acid Chemical compound OC(=O)CCCC[C@H]1CCSS1 AGBQKNBQESQNJD-ZETCQYMHSA-N 0.000 description 1
- 208000000857 Hepatic Insufficiency Diseases 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 206010027439 Metal poisoning Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000003181 encephalopathic effect Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000010501 heavy metal poisoning Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-N hydroperoxyl Chemical compound O[O] OUUQCZGPVNCOIJ-UHFFFAOYSA-N 0.000 description 1
- -1 hydroxyl radical free radical Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 235000015277 pork Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
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CN101607955A true CN101607955A (zh) | 2009-12-23 |
CN101607955B CN101607955B (zh) | 2012-11-28 |
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Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102993167A (zh) * | 2012-11-07 | 2013-03-27 | 台州职业技术学院 | 一种硒辛酸的制备方法 |
CN103058989A (zh) * | 2013-01-30 | 2013-04-24 | 山东齐都药业有限公司 | 一种α-硫辛酸的制备方法 |
CN106365973A (zh) * | 2015-07-20 | 2017-02-01 | 江苏同禾药业有限公司 | 一种硫辛酸中间体的合成方法 |
CN107652264A (zh) * | 2017-09-25 | 2018-02-02 | 苏州华诺医药有限公司 | 硫辛酸杂质a的制备方法 |
CN108484570A (zh) * | 2018-05-15 | 2018-09-04 | 苏州富士莱医药股份有限公司 | 一种制备硫辛酸颗粒的方法及设备 |
CN109574987A (zh) * | 2017-09-29 | 2019-04-05 | 辽宁远大诺康生物制药有限公司 | 硫辛酸的制备方法及硫辛酸在制备治疗少精症的药物中的应用 |
CN110118835A (zh) * | 2019-05-29 | 2019-08-13 | 北京悦康科创医药科技股份有限公司 | 一种高效液相色谱法测定硫辛酸注射液有关物质的方法 |
CN111320603A (zh) * | 2018-12-13 | 2020-06-23 | 江苏同禾药业有限公司 | 一种硫辛酸工艺杂质的制备方法 |
CN112480065A (zh) * | 2020-12-15 | 2021-03-12 | 苏州富士莱医药股份有限公司 | 一种硫辛酸杂质的制备方法 |
CN113292533A (zh) * | 2021-05-25 | 2021-08-24 | 四川智强医药科技开发有限公司 | 硫辛酸中聚合物杂质的纯化方法 |
WO2022045212A1 (ja) * | 2020-08-27 | 2022-03-03 | 協和ファーマケミカル株式会社 | トリスルフィド化合物及びその包接体 |
CN115716817A (zh) * | 2022-11-22 | 2023-02-28 | 国药集团威奇达药业有限公司 | 6,8-环三硫辛酸的制备方法 |
CN115772155A (zh) * | 2021-09-07 | 2023-03-10 | 山东新时代药业有限公司 | 一种α-硫辛酸中间体的制备方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100375745C (zh) * | 2005-12-21 | 2008-03-19 | 重庆药友制药有限责任公司 | 硫辛酸的精制方法 |
-
2008
- 2008-06-18 CN CN2008100391404A patent/CN101607955B/zh active Active
Cited By (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102993167A (zh) * | 2012-11-07 | 2013-03-27 | 台州职业技术学院 | 一种硒辛酸的制备方法 |
CN103058989A (zh) * | 2013-01-30 | 2013-04-24 | 山东齐都药业有限公司 | 一种α-硫辛酸的制备方法 |
CN106365973A (zh) * | 2015-07-20 | 2017-02-01 | 江苏同禾药业有限公司 | 一种硫辛酸中间体的合成方法 |
CN106365973B (zh) * | 2015-07-20 | 2018-12-11 | 江苏同禾药业有限公司 | 一种硫辛酸中间体的合成方法 |
CN107652264A (zh) * | 2017-09-25 | 2018-02-02 | 苏州华诺医药有限公司 | 硫辛酸杂质a的制备方法 |
CN109574987A (zh) * | 2017-09-29 | 2019-04-05 | 辽宁远大诺康生物制药有限公司 | 硫辛酸的制备方法及硫辛酸在制备治疗少精症的药物中的应用 |
CN108484570A (zh) * | 2018-05-15 | 2018-09-04 | 苏州富士莱医药股份有限公司 | 一种制备硫辛酸颗粒的方法及设备 |
CN108484570B (zh) * | 2018-05-15 | 2021-05-04 | 苏州富士莱医药股份有限公司 | 一种制备硫辛酸颗粒的方法及设备 |
CN111320603A (zh) * | 2018-12-13 | 2020-06-23 | 江苏同禾药业有限公司 | 一种硫辛酸工艺杂质的制备方法 |
CN110118835A (zh) * | 2019-05-29 | 2019-08-13 | 北京悦康科创医药科技股份有限公司 | 一种高效液相色谱法测定硫辛酸注射液有关物质的方法 |
CN110118835B (zh) * | 2019-05-29 | 2022-02-18 | 北京悦康科创医药科技股份有限公司 | 一种高效液相色谱法测定硫辛酸注射液有关物质的方法 |
WO2022045212A1 (ja) * | 2020-08-27 | 2022-03-03 | 協和ファーマケミカル株式会社 | トリスルフィド化合物及びその包接体 |
CN112480065A (zh) * | 2020-12-15 | 2021-03-12 | 苏州富士莱医药股份有限公司 | 一种硫辛酸杂质的制备方法 |
CN113292533A (zh) * | 2021-05-25 | 2021-08-24 | 四川智强医药科技开发有限公司 | 硫辛酸中聚合物杂质的纯化方法 |
CN113292533B (zh) * | 2021-05-25 | 2024-04-16 | 四川智强医药科技开发有限公司 | 硫辛酸中聚合物杂质的纯化方法 |
CN115772155A (zh) * | 2021-09-07 | 2023-03-10 | 山东新时代药业有限公司 | 一种α-硫辛酸中间体的制备方法 |
CN115772155B (zh) * | 2021-09-07 | 2023-10-24 | 山东新时代药业有限公司 | 一种α-硫辛酸中间体的制备方法 |
CN115716817A (zh) * | 2022-11-22 | 2023-02-28 | 国药集团威奇达药业有限公司 | 6,8-环三硫辛酸的制备方法 |
CN115716817B (zh) * | 2022-11-22 | 2024-04-19 | 国药集团威奇达药业有限公司 | 6,8-环三硫辛酸的制备方法 |
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CN101607955B (zh) | 2012-11-28 |
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Address after: 201507 Shanghai City, Jinshan District Caojing town Yuegong Road No. 108 Patentee after: Shanghai Jinli Pharmaceutical Co.,Ltd. Address before: 201507 Shanghai City, Jinshan District Caojing town Yuegong Road No. 108 Patentee before: SHANGHAI JINLI BIO-TECH. Co.,Ltd. |
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Denomination of invention: A Preparation Method of Low Residual Lipoic Acid Effective date of registration: 20221121 Granted publication date: 20121128 Pledgee: Shanghai Rural Commercial Bank Co.,Ltd. Jinshan sub branch Pledgor: Shanghai Jinli Pharmaceutical Co.,Ltd. Registration number: Y2022310000329 |
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