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1. 发明授权

US06245921B1 Process for the isolation of pseudomonic acid A from pseudomonic acid complex-containing culture broth 失效
标题翻译：用于从含有假单胞菌酸的复合物的培养液中分离假单胞菌酸A的方法
公开(公告)号：US06245921B1
公开(公告)日：2001-06-12
申请号：US09497806
申请日：2000-02-03
申请人： Istvan Barta , Aniko Tegdes , Valeria Szell , Csaba Szabo , Edit Nagy Nee Arvai , Vilmos Keri , David Leonov , IIdiko Lang , Margit Bidlo Nee Igloy , Gyula Jerkovich , Janos Salat
发明人： Istvan Barta , Aniko Tegdes , Valeria Szell , Csaba Szabo , Edit Nagy Nee Arvai , Vilmos Keri , David Leonov , IIdiko Lang , Margit Bidlo Nee Igloy , Gyula Jerkovich , Janos Salat
IPC分类号： C07D31500
CPC分类号： C12P17/162
摘要： A process for the isolation of the pseudomonic acid A antibiotic of pharmaceutical quality from the culture broth of one of the pseudomonic acid A-producing species of the Pseudomonas bacterium genus comprising the extraction of the biosynthesized pseudomonic acid A from the culture broth at acidic pH with a chlorinated aliphatic hydrocarbon or isobutyl acetate, followed by purification, is disclosed. The invention includes processes for purification of the isolated pseudomonic acid A, including (a) by the distribution of the evaporated extract residue between the aqueous-alcohol and some aliphatic or aromatic hydrocarbon, and then the extraction of the increased water-containing aqueous-alcoholic phase with methylene chloride, ethyl acetate, or isobutyl acetate; (b) by the extraction of the extract with aqueous ammonium hydrogen carbonate, alkali metal hydroxide or ammonium hydroxide solution and the acidification of the resulting alkaline aqueous extract, then reextraction again with a chlorinated aliphatic hydrocarbon or isobutyl acetate; and (c) by the concentration of the extract and the recrystallization of the crystalline pseudomonic acid A in a mixture of isobutyl acetate and petroleum ether, or acetonitrile, or aqueous acetonitrile.
摘要翻译：从假单胞菌属的假单胞菌素A产生物种之一的培养液中分离出假单胞菌A抗生素药物质量的方法，包括在酸性pH下从培养液中提取生物合成的假单胞菌酸A，公开了氯化脂族烃或乙酸异丁酯，然后纯化。本发明包括纯化分离的假单胞菌酸A的方法，包括（a）通过在含水醇和某些脂族或芳族烃之间分配蒸发的提取物残渣，然后提取含水的含水醇与二氯甲烷，乙酸乙酯或乙酸异丁酯反应; （b）通过用碳酸氢铵水溶液，碱金属氢氧化物或氢氧化铵溶液萃取提取物，并将得到的碱性水提取物酸化，然后用氯化脂族烃或乙酸异丁酯再次萃取; 和（c）通过提取物的浓度和结晶假单胞菌酸A在乙酸异丁酯和石油醚或乙腈或乙腈水溶液的混合物中的重结晶。

2. 发明授权

US06696599B2 Microbial process for preparing pravastatin 失效
标题翻译：制备普伐他汀的微生物过程
公开(公告)号：US06696599B2
公开(公告)日：2004-02-24
申请号：US10437058
申请日：2003-05-14
申请人： Antonia Jekkel , Attila Konya , Istvan Barta , Eva Ilkoy , Gyorgy Somogyi , Gabor Ambrus , Gyula Horvath , Karoly Albrecht , Istvan Szabo , Julianna Mozes Nee Suto , Janso Salat , Attila Andor , Laszlo Birincsik , Sandor Boros , Ildiko Lang , Margit Bidlo Nee Igloy
发明人： Antonia Jekkel , Attila Konya , Istvan Barta , Eva Ilkoy , Gyorgy Somogyi , Gabor Ambrus , Gyula Horvath , Karoly Albrecht , Istvan Szabo , Julianna Mozes Nee Suto , Janso Salat , Attila Andor , Laszlo Birincsik , Sandor Boros , Ildiko Lang , Margit Bidlo Nee Igloy
IPC分类号： C07C6702
CPC分类号： C12R1/645 , C12P7/62
摘要： The present invention relates to a new microbial process for the preparation of the compound formula (I) from a compound of general formula (II) wherein R stands for an alkali metal or ammonium ion, by the submerged cultivation of a mold strain able to 6&bgr;-hydroxylate a compound of the Formula (II) in aerobic fermentation and by the separation and purification of the product of Formula (I) formed in the course of the bioconversion. The process comprises cultivating a strain of Mortierella maculata filamentous mold species that is able to 6&bgr;-hydroxylate a compound of the general Formula (II), on a nutrient medium containing assimilable carbon and nitrogen sources and mineral salts and separating the product formed from the fermentation broth, then isolating the compound of formula (I) and purifying the same. Novel strains of Mortierella maculata are also disclosed.
摘要翻译：本发明涉及一种由通式（II）的化合物制备式（I）化合物的新的微生物方法，其中R代表碱金属或铵离子，通过浸没式培养能够提供6β 在需氧发酵中通过分解和纯化在生物转化过程中形成的式（I）的产物来氢化式（II）化合物。该方法包括在含有可吸收的碳和氮源和矿物盐的营养培养基上培养能够将通式（II）的化合物6β-羟基化的高山被孢霉丝状菌种的菌株，并分离由发酵形成的产物肉汤，然后分离式（I）化合物并纯化。还公开了高山被孢霉的新型菌株。

3. 发明授权

US06750366B2 Microbial process for preparing pravastatin 失效
标题翻译：制备普伐他汀的微生物过程
公开(公告)号：US06750366B2
公开(公告)日：2004-06-15
申请号：US10011176
申请日：2001-12-05
申请人： Antonia Jekkel , Attila Konya , Istvan Barta , Eva Ilkoy , Gyorgy Somogyi , Gabor Ambrus , Gyula Horvath , Karoly Albrecht , Istvan Szabo , Julianna Mozes Nee Suto , Janso Salat , Attila Andor , Laszlo Birinesik , Sandor Boros , Ildiko Lang , Margit Bidlo Nee Igloy
发明人： Antonia Jekkel , Attila Konya , Istvan Barta , Eva Ilkoy , Gyorgy Somogyi , Gabor Ambrus , Gyula Horvath , Karoly Albrecht , Istvan Szabo , Julianna Mozes Nee Suto , Janso Salat , Attila Andor , Laszlo Birinesik , Sandor Boros , Ildiko Lang , Margit Bidlo Nee Igloy
IPC分类号： C07C6902
CPC分类号： C12R1/645 , C12P7/62
摘要： The present invention relates to a new microbial process for the preparation of the compound formula (I): from a compound of general formula (II): wherein R stands for an alkali metal or ammonium ion, by the submerged cultivation of a mold strain able to 6&bgr;-hydroxylate a compound of the Formula (II) in aerobic fermentation and by the separation and purification of the product of Formula (I) formed in the course of the bioconversion. The process comprises cultivating a strain of Mortierella maculata filamentous mold species that is able to 6&bgr;-hydroxylate a compound of the general Formula (II), on a nutrient medium containing assimilable carbon and nitrogen sources and mineral salts and separating the product formed from the fermentation broth, then isolating the compound of formula (I) and purifying the same. Novel strains of Mortierella maculata are also disclosed.
摘要翻译：本发明涉及一种制备式（I）化合物的新的微生物方法：由通式（II）的化合物：其中R代表碱金属或铵离子，通过浸没式培养可变形的模具在有氧发酵中通过分解和纯化在生物转化过程中形成的式（I）的产物来将式（II）的化合物改性为6β-羟基化。该方法包括在含有可吸收的碳和氮源和矿物盐的营养培养基上培养能够将通式（II）的化合物6β-羟基化的高山被孢霉丝状菌种的菌株，并分离由发酵形成的产物肉汤，然后分离式（I）化合物并纯化。还公开了高山被孢霉的新型菌株。

4. 发明授权

US06682913B1 Microbial process for preparing pravastatin 失效
公开(公告)号：US06682913B1
公开(公告)日：2004-01-27
申请号：US09497805
申请日：2000-02-03
申请人： Antonia Jekkel , Attila Konya , Istvan Barta , Eva Ilkoy , Gyorgy Somogyi , Gabor Ambrus , Gyula Horvath , Karoly Albrecht , Istvan Szabo , Julianna Mozes nee Suto , Janso Salat , Attila Andor , Laszlo Birincsik , Sandor Boros , Ildiko Lang , Margit Bidlo nee Igloy
发明人： Antonia Jekkel , Attila Konya , Istvan Barta , Eva Ilkoy , Gyorgy Somogyi , Gabor Ambrus , Gyula Horvath , Karoly Albrecht , Istvan Szabo , Julianna Mozes nee Suto , Janso Salat , Attila Andor , Laszlo Birincsik , Sandor Boros , Ildiko Lang , Margit Bidlo nee Igloy
IPC分类号： C12P762
CPC分类号： C12R1/645 , C12P7/62
摘要： The present invention relates to a new microbial process for the preparation of the compound formula (I) from a compound of general formula (II) wherein R stands for an alkali metal or ammonium ion, by the submerged cultivation of a mold strain able to 6&bgr;-hydroxylate a compound of the Formula (II) in aerobic fermentation and by the separation and purification of the product of Formula (I) formed in the course of the bioconversion. The process comprises cultivating a strain of Mortierella maculata filamentous mold species that is able to 6&bgr;-hydroxylate a compound of the general Formula (II), on a nutrient medium containing assimilable carbon and nitrogen sources and mineral salts and separating the product formed from the fermentation broth, then isolating the compound of formula (I) and purifying the same. Novel strains of Mortierella maculata are also disclosed.

5. 发明授权

US06509177B1 Process for the preparation of pseudomonic acid A antibiotic by microbiological method 失效
标题翻译：通过微生物法制备假单胞菌A抗生素的方法
公开(公告)号：US06509177B1
公开(公告)日：2003-01-21
申请号：US09497807
申请日：2000-02-03
申请人： Valeria Szell , Ildiko Lang , Istvan Barta , Aniko Tedges , Karoly Albrecht , Julianna Mozes Nee Suto , Istvan M. Szabo , Magdolna Petroczki , Janos Erdei , Eva Gulyas , Gabor Balogh
发明人： Valeria Szell , Ildiko Lang , Istvan Barta , Aniko Tedges , Karoly Albrecht , Julianna Mozes Nee Suto , Istvan M. Szabo , Magdolna Petroczki , Janos Erdei , Eva Gulyas , Gabor Balogh
IPC分类号： C12P1706
CPC分类号： C12R1/38 , C12P17/162
摘要： A procedure for the preparation of pseudomonic acid A comprising submerged cultivation of a Pseudomonas bacterium strain capable of biosynthesis of the substantially pure pseudomonic acid A in aerated conditions via fermentation; and isolation of the desired compound is disclosed. In particular, the procedure of the present invention comprises cultivation of the Pseudomonas sp. bacterium strain No. 19/26 deposited under accession No. NCAIM(P)B 001235 in the National Collection of the Agricultural and Industrial Microorganisms, Budapest, Hungary, or its pseudomonic acid A-producing mutant or variant, on a medium at a temperature of between about 20° C. and 30° C. containing organic nitrogen and carbon sources and, optionally, mineral salts.
摘要翻译：制备假单胞菌酸A的方法，其包括通过发酵在充气条件下能够生物合成基本上纯的假单胞菌酸A的假单胞菌属细菌菌株的浸没培养; 并公开了所需化合物的分离。特别地，本发明的方法包括培养假单胞菌属在保藏号NCAIM（P）B 001235，在匈牙利布达佩斯，布达佩斯的农业和工业微生物国家收藏品或其假肌酸A产生的突变体或变体中保藏的细菌株19/26在温度约20℃至30℃，含有机氮和碳源，以及任选的无机盐。

6. 发明授权

US06506591B2 Process for the preparation of pseudomonic acid a antibiotic by microbiological method 失效
公开(公告)号：US06506591B2
公开(公告)日：2003-01-14
申请号：US09975796
申请日：2001-10-11
申请人： Valeria Szell , Ildiko Lang , Istvan Barta , Aniko Tedges , Karoly Albrecht , Julianna Mozes Nee Suto , Istvan M. Szabo , Magdolna Petroczki , Janos Erdei , Eva Gulyas , Gabor Balogh
发明人： Valeria Szell , Ildiko Lang , Istvan Barta , Aniko Tedges , Karoly Albrecht , Julianna Mozes Nee Suto , Istvan M. Szabo , Magdolna Petroczki , Janos Erdei , Eva Gulyas , Gabor Balogh
IPC分类号： C12N120
CPC分类号： C12R1/38 , C12P17/162
摘要： A procedure for the preparation of pseudomonic acid A comprising submerged cultivation of a Pseudomonas bacterium strain capable of biosynthesis of the substantially pure pseudomonic acid A in aerated conditions via fermentation; and isolation of the desired compound is disclosed. In particular, the procedure of the present invention comprises cultivation of the Pseudomonas sp. bacterium strain No. 19/26 deposited under accession No. NCAIM(P)B 001235 in the National Collection of the Agricultural and Industrial Microorganisms, Budapest, Hungary, or its pseudomonic acid A-producing mutant or variant, on a medium at a temperature of between about 20° C. and 30° C. containing organic nitrogen and carbon sources and, optionally, mineral salts.

7. 发明授权

US4369251A Method for the production of sisomicin 失效
标题翻译：西索米星生产方法
公开(公告)号：US4369251A
公开(公告)日：1983-01-18
申请号：US214445
申请日：1980-12-08
申请人： Miklos Jarai , Sandor Piukovich , Sandor Istvan , Istvan Gado , Valeria Szell , Istvan Barta
发明人： Miklos Jarai , Sandor Piukovich , Sandor Istvan , Istvan Gado , Valeria Szell , Istvan Barta
IPC分类号： C12P19/54 , C07H15/236 , C12P19/48 , C12R1/29
CPC分类号： C12R1/29 , C07H15/236 , C12P19/48 , Y10S435/867
摘要： Sisomicin is produced by culturing Micromonospora danubienis.
摘要翻译：西索米星是通过培养小单孢菌来生产的。

8. 发明授权

US07078223B2 Process for the preparation of pseudomonic acid a antibiotic by microbiological method 失效
公开(公告)号：US07078223B2
公开(公告)日：2006-07-18
申请号：US10293675
申请日：2002-11-12
申请人： Valeria Szell , Ildiko Lang , Istvan Barta , Aniko Tedges , Karoly Albrecht , Julianna Mozes Nee Suto , Istvan M. Szabo , Magdolna Petroczki , Janos Erdei , Eva Gulyas , Gabor Balogh
发明人： Valeria Szell , Ildiko Lang , Istvan Barta , Aniko Tedges , Karoly Albrecht , Julianna Mozes Nee Suto , Istvan M. Szabo , Magdolna Petroczki , Janos Erdei , Eva Gulyas , Gabor Balogh
IPC分类号： C12N1/20 , C12P17/06
CPC分类号： C12R1/38 , C12P17/162
摘要： A procedure for the preparation of pseudomonic acid A comprising submerged cultivation of a Pseudomonas bacterium strain capable of biosynthesis of the substantially pure pseudomonic acid A in aerated conditions via fermentation; and isolation of the desired compound is disclosed. In particular, the procedure of the present invention comprises cultivation of the Pseudomonas sp. bacterium strain No. 19/26 deposited under accession No. NCAIM(P)B 001235 in the National Collection of the Agricultural and Industrial Microorganisms, Budapest, Hungary, or its pseudomonic acid A-producing mutant or variant, on a medium at a temperature of between about 20° C. and 30° C. containing organic nitrogen and carbon sources and, optionally, mineral salts.

9. 发明授权

US4371622A Micromonospora culture 失效
标题翻译：小单孢菌培养
公开(公告)号：US4371622A
公开(公告)日：1983-02-01
申请号：US116916
申请日：1980-01-30
申请人： Miklos Jarai , Sandor Piukovich , Sandor Istvan , Istvan Gado , Valeria Szell , Istvan Barta
发明人： Miklos Jarai , Sandor Piukovich , Sandor Istvan , Istvan Gado , Valeria Szell , Istvan Barta
IPC分类号： C12P19/54 , C07H15/236 , C12P19/48 , C12R1/29 , C12N1/20
CPC分类号： C12R1/29 , C07H15/236 , C12P19/48 , Y10S435/867
摘要： Micromonospora danubiensis, a new species, having the capability of producing sisomicin.
摘要翻译：一种具有生产西索霉素能力的新品种小单孢菌（Micomonospora danubiensis）。

10. 发明申请

US20050124051A1 Hydroxylation of compactin to pravatatin by micromonospora 审中-公开
标题翻译：通过微单孢菌素将致密蛋白羟基化为普伐他汀
公开(公告)号：US20050124051A1
公开(公告)日：2005-06-09
申请号：US11014658
申请日：2004-12-16
申请人： Antonia Jekkel , Gabor Ambrus , Eva Ilkoy , Ildiko Horvath , Attila Konya , Istvan Szabo , Zsuzsanna Nagy , Gyula Horvath , Julia Mozes , Istvan Barta , Gyorgy Somogyi , Janos Salat , Sandor Boros
发明人： Antonia Jekkel , Gabor Ambrus , Eva Ilkoy , Ildiko Horvath , Attila Konya , Istvan Szabo , Zsuzsanna Nagy , Gyula Horvath , Julia Mozes , Istvan Barta , Gyorgy Somogyi , Janos Salat , Sandor Boros
IPC分类号： C12P7/62 , C07C69/30 , C12P1/04 , C12P7/42 , C12P17/06 , C12R1/29 , C12R1/31 , C12N1/21 , C12N9/18
CPC分类号： C12R1/29 , C12P7/42 , C12P17/06
摘要： The present invention relates to a new microbial process for the preparation of compound of formula (I) from a compound of general formula (II) wherein R stands for an alkali metal or ammonium ion, by the submerged culture of a strain which is able to 6β-hydroxylate the compound of formula (II) in aerobic fermentation and by the separation and purification of the product of formula (I) formed in the course of the biocoversion. The latter comprises the cultivation of a Micromonospora strain which is able to 6β-hydroxylate a compound of general formula (II)—wherein R is as defined above—at 25-32° C. on a nutrient medium containing available carbon—and nitrogen sources and mineral salts, thereafter feeding the substrate to be transformed into the developing culture, then hydroxilating the substrate until finishing of the bioconversion, then separating the compound of formula (I) from the culture broth and, if desired, purifying the same.
摘要翻译：本发明涉及一种由通式（II）化合物制备式（I）化合物的新型微生物方法，其中R代表碱金属或铵离子，通过浸没培养的能够在好氧发酵中通过分解和纯化在生物转化过程中形成的式（I）的产物，使式（II）化合物6β-羟化。后者包括培养微孢子虫菌株，其能够在含有可用碳源和氮源的营养培养基上在25-32℃下将通式（II）化合物（其中R如上定义）6β-羟基化然后将待转化的底物喂入显影培养物，然后将底物氢化，直到生物转化完成，然后从培养液中分离式（I）化合物，如果需要，将其纯化。

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