SK285726B6 - Hydroxylácia compactinu na pravastatin s použitímmikromonospór - Google Patents
Hydroxylácia compactinu na pravastatin s použitímmikromonospór Download PDFInfo
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- SK285726B6 SK285726B6 SK49-2002A SK492002A SK285726B6 SK 285726 B6 SK285726 B6 SK 285726B6 SK 492002 A SK492002 A SK 492002A SK 285726 B6 SK285726 B6 SK 285726B6
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- micromonospora
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
- C12P7/42—Hydroxy-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/06—Oxygen as only ring hetero atoms containing a six-membered hetero ring, e.g. fluorescein
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/29—Micromonospora
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9902352A HUP9902352A1 (hu) | 1999-07-12 | 1999-07-12 | Eljárás pravasztatin mikrobiológiai előállítására |
| PCT/HU2000/000066 WO2001004340A1 (en) | 1999-07-12 | 2000-06-29 | Hydroxylation of compactin to pravastatin by micromonospora |
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| SK492002A3 SK492002A3 (sk) | 2005-03-04 |
| SK285726B6 true SK285726B6 (sk) | 2007-07-06 |
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| SK49-2002A SK285726B6 (sk) | 1999-07-12 | 2000-06-29 | Hydroxylácia compactinu na pravastatin s použitímmikromonospór |
| SK61-2002A SK612002A3 (en) | 1999-07-12 | 2000-07-11 | Microbial process for preparing pravastatin |
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| SK61-2002A SK612002A3 (en) | 1999-07-12 | 2000-07-11 | Microbial process for preparing pravastatin |
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| EP (3) | EP1327689A1 (da) |
| JP (2) | JP4531315B2 (da) |
| KR (2) | KR100479837B1 (da) |
| CN (2) | CN1399686A (da) |
| AP (1) | AP1405A (da) |
| AT (1) | ATE243262T1 (da) |
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| BR (1) | BR0013156A (da) |
| CA (2) | CA2379015A1 (da) |
| CZ (2) | CZ297009B6 (da) |
| DE (1) | DE60003424T2 (da) |
| DK (1) | DK1190087T3 (da) |
| ES (1) | ES2200891T3 (da) |
| HR (1) | HRP20020028B1 (da) |
| HU (1) | HUP9902352A1 (da) |
| IL (2) | IL147583A0 (da) |
| IS (1) | IS2138B (da) |
| MX (1) | MXPA02000356A (da) |
| NO (1) | NO20020119L (da) |
| NZ (1) | NZ516563A (da) |
| OA (1) | OA12150A (da) |
| PL (2) | PL353493A1 (da) |
| PT (1) | PT1190087E (da) |
| RU (2) | RU2235780C2 (da) |
| SK (2) | SK285726B6 (da) |
| TR (1) | TR200200726T2 (da) |
| UA (1) | UA67854C2 (da) |
| WO (2) | WO2001004340A1 (da) |
| YU (1) | YU2002A (da) |
| ZA (1) | ZA200200273B (da) |
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| SI9800046A (sl) | 1998-02-18 | 1999-08-31 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | Postopek za pridobivanje inhibitorjev HMG-CoA reduktaze visoke čistosti |
| HUP9902352A1 (hu) * | 1999-07-12 | 2000-09-28 | Gyógyszerkutató Intézet Kft. | Eljárás pravasztatin mikrobiológiai előállítására |
| JP3881240B2 (ja) | 1999-11-30 | 2007-02-14 | テバ ジョジセルジャール ザ−トケルエン ムケド レ−スベニュタ−ルシャシャ−グ | 醗酵ブロスからスタチン化合物を回収するための方法 |
| AU779306B2 (en) | 1999-12-14 | 2005-01-13 | Teva Gyogyszergyar Reszvenytarsasag | Novel forms of pravastatin sodium |
| CN1468098A (zh) * | 2000-10-05 | 2004-01-14 | �ݰ¸Ƕ�ҩ������˾ | 基本上无普伐他汀内酯和表普伐他汀的普伐他汀钠和包含普伐他汀钠的组合物 |
| JP3236282B1 (ja) * | 2000-10-16 | 2001-12-10 | 三共株式会社 | プラバスタチンを精製する方法 |
| EP1357807B1 (en) * | 2001-02-09 | 2007-03-14 | Unilever N.V. | Food product comprising soy protein and statins |
| JP2003026634A (ja) * | 2001-07-17 | 2003-01-29 | Mercian Corp | プラバスタチンナトリウム塩の製造方法 |
| US6716615B2 (en) | 2002-02-27 | 2004-04-06 | Yung Shin Pharmaceutical Ind. Co., Ltd. | Strains of saccharaothrix, process for producing pravastatin using the strains and isolation process of (HMG)-CoA reductase |
| EP1452602A1 (en) * | 2003-02-25 | 2004-09-01 | Antibiotic Co., | Method for production of pravastatin by fermentation |
| CN1244688C (zh) * | 2003-07-09 | 2006-03-08 | 上海天伟生物制药有限公司 | 生产普伐他汀钠的微生物和方法 |
| WO2005051372A2 (en) | 2003-11-24 | 2005-06-09 | Teva Gyógyszergyár Zártköruen Muködo Részvénytársaság | Method of purifying pravastatin |
| MY161108A (en) * | 2008-02-06 | 2017-04-14 | Biocon Ltd | Fermentation medias and processes thereof |
| RU2522806C1 (ru) * | 2012-11-27 | 2014-07-20 | Федеральное государственное бюджетное учреждение науки Центр "Биоинженерия" Российской академии наук | Усовершенствованный способ очистки правастатина |
| JP6441599B2 (ja) * | 2014-07-14 | 2018-12-19 | 合同酒精株式会社 | プラバスタチンの製造法 |
| CN114031496B (zh) * | 2021-11-30 | 2024-09-27 | 广东蓝宝制药有限公司 | 一种高纯度普伐他汀1,1,3,3-四甲基丁胺的制备方法 |
| CN114133331A (zh) * | 2021-12-10 | 2022-03-04 | 广东蓝宝制药有限公司 | 一种回收获得高纯度普伐他汀酯的方法 |
| CN116694497B (zh) * | 2022-12-25 | 2024-10-18 | 塔里木大学 | 一株转化甘油和甘氨酸的放线菌 |
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|---|---|---|---|---|
| MX7065E (es) | 1980-06-06 | 1987-04-10 | Sankyo Co | Un procedimiento microbiologico para preparar derivados de ml-236b |
| JPS5810572A (ja) | 1981-07-07 | 1983-01-21 | Sankyo Co Ltd | Ｍｌ−２３６ｂ誘導体およびその製造法 |
| JPS5889191A (ja) | 1981-11-20 | 1983-05-27 | Sankyo Co Ltd | ３−ヒドロキシ−ｍｌ−２３６ｂ誘導体の製造法 |
| JPS59175450A (ja) * | 1983-03-24 | 1984-10-04 | Sankyo Co Ltd | Ｍｌ−２３６ｂ誘導体 |
| US5179013A (en) * | 1987-02-02 | 1993-01-12 | Sankyo Company, Limited | Cytochrome P-450 enzymes |
| JPH06253853A (ja) * | 1993-03-09 | 1994-09-13 | Asahi Chem Ind Co Ltd | マクロライド抗生物質生合成遺伝子を含有するｄｎａ |
| US6043064A (en) * | 1993-10-22 | 2000-03-28 | Bristol-Myers Squibb Company | Enzymatic hydroxylation process for the preparation of HMG-CoA reductase inhibitors and intermediates thereof |
| JPH0889277A (ja) * | 1994-09-28 | 1996-04-09 | Taisho Pharmaceut Co Ltd | １２−ヒドロキシ−６−ｏ−アルキルエリスロマイシン及びその類縁体の製造方法 |
| JPH08149986A (ja) * | 1994-09-28 | 1996-06-11 | Taisho Pharmaceut Co Ltd | １２−ヒドロキシ−６−ｏ−アルキルエリスロマイシン及びその類縁体の製造方法 |
| US5942423A (en) * | 1995-06-07 | 1999-08-24 | Massachusetts Institute Of Technology | Conversion of compactin to pravastatin by actinomadura |
| SI20072A (sl) * | 1998-09-18 | 2000-04-30 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | Postopek za pridobivanje inhibitorjev HMG-CoA reduktaze |
| US6682913B1 (en) * | 1999-02-03 | 2004-01-27 | Institute For Drug Research Ltd. | Microbial process for preparing pravastatin |
| HUP9902352A1 (hu) * | 1999-07-12 | 2000-09-28 | Gyógyszerkutató Intézet Kft. | Eljárás pravasztatin mikrobiológiai előállítására |
| IN191580B (da) * | 1999-12-17 | 2003-12-06 | Ranbaxy Lab Ltd |
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1999
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2000
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