CN104131061B - 一种土霉素季铵盐的制备方法 - Google Patents
一种土霉素季铵盐的制备方法 Download PDFInfo
- Publication number
- CN104131061B CN104131061B CN201410382751.4A CN201410382751A CN104131061B CN 104131061 B CN104131061 B CN 104131061B CN 201410382751 A CN201410382751 A CN 201410382751A CN 104131061 B CN104131061 B CN 104131061B
- Authority
- CN
- China
- Prior art keywords
- oxytetracycline
- quaternary ammonium
- ammonium salt
- preparation
- spore
- 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.)
- Active
Links
- 239000004100 Oxytetracycline Substances 0.000 title claims abstract description 37
- 229960000625 oxytetracycline Drugs 0.000 title claims abstract description 37
- 235000019366 oxytetracycline Nutrition 0.000 title claims abstract description 37
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 title claims abstract description 37
- -1 oxytetracycline quaternary ammonium salt Chemical class 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000001556 precipitation Methods 0.000 claims abstract description 9
- 238000001953 recrystallisation Methods 0.000 claims abstract description 8
- 238000000746 purification Methods 0.000 claims abstract description 7
- 229910021529 ammonia Inorganic materials 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 230000033228 biological regulation Effects 0.000 claims abstract description 5
- 238000001035 drying Methods 0.000 claims abstract description 5
- 238000000855 fermentation Methods 0.000 claims description 27
- 230000004151 fermentation Effects 0.000 claims description 27
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 21
- 239000012531 culture fluid Substances 0.000 claims description 20
- 239000000706 filtrate Substances 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 12
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 235000006408 oxalic acid Nutrition 0.000 claims description 7
- 102000004169 proteins and genes Human genes 0.000 claims description 7
- 108090000623 proteins and genes Proteins 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
- 229910052742 iron Inorganic materials 0.000 claims description 5
- 239000002808 molecular sieve Substances 0.000 claims description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 5
- 239000004576 sand Substances 0.000 claims description 5
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 229960001763 zinc sulfate Drugs 0.000 claims description 5
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 5
- 229920001817 Agar Polymers 0.000 claims description 4
- 239000008272 agar Substances 0.000 claims description 4
- 230000003321 amplification Effects 0.000 claims description 4
- 229910021538 borax Inorganic materials 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- 150000008282 halocarbons Chemical class 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 4
- 239000000276 potassium ferrocyanide Substances 0.000 claims description 4
- 239000011347 resin Substances 0.000 claims description 4
- 229920005989 resin Polymers 0.000 claims description 4
- 239000004328 sodium tetraborate Substances 0.000 claims description 4
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 claims description 4
- 238000012546 transfer Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 4
- 239000013530 defoamer Substances 0.000 claims description 3
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 claims description 2
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 claims description 2
- 229910000388 diammonium phosphate Inorganic materials 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 6
- 239000000047 product Substances 0.000 abstract description 6
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 239000002244 precipitate Substances 0.000 abstract description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 abstract 1
- OWFJMIVZYSDULZ-PXOLEDIWSA-N (4s,4ar,5s,5ar,6s,12ar)-4-(dimethylamino)-1,5,6,10,11,12a-hexahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O OWFJMIVZYSDULZ-PXOLEDIWSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 229940072172 tetracycline antibiotic Drugs 0.000 description 2
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 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 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241001312524 Streptococcus viridans Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 238000009360 aquaculture Methods 0.000 description 1
- 244000144974 aquaculture Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003197 catalytic effect Effects 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
- 230000001276 controlling effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229930185127 geomycin Natural products 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000005826 halohydrocarbons Chemical class 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- KQPMFNHZHBLVRR-UHFFFAOYSA-N oxalic acid;hydrochloride Chemical compound Cl.OC(=O)C(O)=O KQPMFNHZHBLVRR-UHFFFAOYSA-N 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical class N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 235000015099 wheat brans Nutrition 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410382751.4A CN104131061B (zh) | 2014-08-06 | 2014-08-06 | 一种土霉素季铵盐的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410382751.4A CN104131061B (zh) | 2014-08-06 | 2014-08-06 | 一种土霉素季铵盐的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104131061A CN104131061A (zh) | 2014-11-05 |
CN104131061B true CN104131061B (zh) | 2016-11-23 |
Family
ID=51803911
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410382751.4A Active CN104131061B (zh) | 2014-08-06 | 2014-08-06 | 一种土霉素季铵盐的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN104131061B (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104894203A (zh) * | 2015-05-27 | 2015-09-09 | 合肥卓元科技服务有限公司 | 一种高纯度土霉素的生产工艺 |
CN108841910B (zh) * | 2018-05-29 | 2020-10-13 | 江西国药有限责任公司 | 一种土霉素季铵盐的制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101914035A (zh) * | 2010-08-27 | 2010-12-15 | 扬州联博药业有限公司 | 一种盐酸土霉素的制备方法 |
CN102702017A (zh) * | 2012-06-21 | 2012-10-03 | 河北圣雪大成制药有限责任公司 | 一种烷基三甲铵钙土霉素的制备方法 |
CN103243133A (zh) * | 2013-04-28 | 2013-08-14 | 内蒙古开盛生物科技有限公司 | 一种将盐酸与草酸并用提取土霉素碱的生产工艺 |
-
2014
- 2014-08-06 CN CN201410382751.4A patent/CN104131061B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101914035A (zh) * | 2010-08-27 | 2010-12-15 | 扬州联博药业有限公司 | 一种盐酸土霉素的制备方法 |
CN102702017A (zh) * | 2012-06-21 | 2012-10-03 | 河北圣雪大成制药有限责任公司 | 一种烷基三甲铵钙土霉素的制备方法 |
CN103243133A (zh) * | 2013-04-28 | 2013-08-14 | 内蒙古开盛生物科技有限公司 | 一种将盐酸与草酸并用提取土霉素碱的生产工艺 |
Non-Patent Citations (1)
Title |
---|
Chemistry of the Tetracycline Antibiotics. I. Quaternary Derivatives;James H. Boothe,et al.;《 J. Am. Chem. Soc.》;19580405;第80卷(第7期);第1656页左栏倒数第2段 * |
Also Published As
Publication number | Publication date |
---|---|
CN104131061A (zh) | 2014-11-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106978368B (zh) | 解鸟氨酸拉乌尔菌及其应用 | |
KR20090100406A (ko) | 염기성 아미노산 염산염 결정의 수득 방법 | |
CN105658802A (zh) | 尸胺的纯化 | |
CN107118976A (zh) | 阴沟肠杆菌及其应用 | |
CN104131061B (zh) | 一种土霉素季铵盐的制备方法 | |
EP1927586A1 (en) | Process for producing 5-aminolevulinic acid hydrochloride | |
CN105612257B (zh) | 使用高沸点溶剂的尸胺纯化 | |
CN104894203A (zh) | 一种高纯度土霉素的生产工艺 | |
RU2573935C2 (ru) | Способ выделения и очистки 1,4-диаминобутана из ферментационного раствора | |
CN102586384A (zh) | 一种通过dl-氨基酸去消旋化制备d-氨基酸的生物催化方法 | |
CN106745813A (zh) | 有机酸水体改良剂及其制备方法 | |
CN109096129B (zh) | 一种左旋肉碱酒石酸盐的制备方法 | |
JPS61212249A (ja) | 飼料用組成物 | |
EP1474375A1 (en) | Process for the isolation of polyhydroxy cyclic carboxylic acids | |
US3966796A (en) | N-chloro-amino acid derivatives activity | |
JPH03130084A (ja) | トレハロースの製造法 | |
CN105036330A (zh) | 一种结晶型精酮合剂的制备方法 | |
CN113862179A (zh) | 一种沼泽红假单胞菌及其制备5-ala的用途和方法 | |
CN101580858A (zh) | 一种dl-丙氨酸的酶法生产工艺 | |
CN107142227B (zh) | 产酸克雷伯菌及其应用 | |
CN110079565A (zh) | 一种可提高转化率的豆腐黄浆水发酵生产氨基酸的方法 | |
CN105073999A (zh) | 5-氨基乙酰丙酸或其盐的制造方法 | |
JPS5840462B2 (ja) | 微細藻類の培養方法 | |
JPH07313176A (ja) | 新規微生物および該微生物を用いた 2,6−ナフタレンジカルボン酸の製造法 | |
CN115181032B (zh) | 一种基于选择性共结晶/成盐拆分dl-缬氨酸外消旋化合物的方法 |
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 | ||
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20201214 Address after: 2 Nanjing middle road, Yangzi River International Chemical Industry Park, Suzhou, Jiangsu Province Patentee after: ZHANG JIA GANG VINSCE BIO-PHARM Co.,Ltd. Address before: Building D, No.7, Guangdong Road, free trade zone, Zhangjiagang City, Jiangsu Province Patentee before: JIANGSU SWELLXIN BIO-PHARM. Pty Ltd. |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A preparation method of oxytetracycline quaternary ammonium salt Effective date of registration: 20210930 Granted publication date: 20161123 Pledgee: Agricultural Bank of China Limited Zhangjiagang branch Pledgor: ZHANG JIA GANG VINSCE BIO-PHARM Co.,Ltd. Registration number: Y2021320010400 |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
CP01 | Change in the name or title of a patent holder |
Address after: 2 Nanjing middle road, Yangzi River International Chemical Industry Park, Suzhou, Jiangsu Province Patentee after: Weisheng Biomedical (Suzhou) Co.,Ltd. Address before: 2 Nanjing middle road, Yangzi River International Chemical Industry Park, Suzhou, Jiangsu Province Patentee before: ZHANG JIA GANG VINSCE BIO-PHARM Co.,Ltd. Address after: 2 Nanjing middle road, Yangzi River International Chemical Industry Park, Suzhou, Jiangsu Province Patentee after: Wison Biomedical (Suzhou) Co.,Ltd. Address before: 2 Nanjing middle road, Yangzi River International Chemical Industry Park, Suzhou, Jiangsu Province Patentee before: Weisheng Biomedical (Suzhou) Co.,Ltd. |
|
CP01 | Change in the name or title of a patent holder | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20221031 Granted publication date: 20161123 Pledgee: Agricultural Bank of China Limited Zhangjiagang branch Pledgor: ZHANG JIA GANG VINSCE BIO-PHARM Co.,Ltd. Registration number: Y2021320010400 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right |