CN105671110A - Method of producing dalbavancin precursor A40926 - Google Patents
Method of producing dalbavancin precursor A40926 Download PDFInfo
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Abstract
The invention discloses a method of producing a dalbavancin precursor A40926. In particular, during a fermentation cultivation proves, 10-methyl undecanoic acid, or several 10-methyl undecanoic undecanoate solutions, is flow-fed to a fermentation liquid to increase the yield of the dalbavancin precursor A40926. The method is simple in operation, greatly increases fermentation yield, reduces production cost and is suitable for industrial production.
Description
Technical field
The present invention relates to field of biological pharmacy, in particular it relates to a kind of method producing dalbavancin precursor A40926.
Background technology
Dalbavancin (Dalbavancin) is a new generation's glycopeptide antibiotics, and vancomycin, ramoplanin belong to same class. This class antibiotic is used for treating those the most ticklish antibacterials to be infected, such as methicillin-resistant S staphylococcus (MRSA) and methicillin resistance staphylococcus epidermidis (MRSE). Experiment in vitro shows, dalbavancin is except the gram positive bacteria bactericidal activity that clinic is common strengthens, and its half-life is longer, and penetration into tissue is better, and such patient administration has greater flexibility. So far the clinical front and clinical studies show carried out, dalbavancin is one of antibiotic that MRSA and MRSE activity is the strongest, and does not cause significant dose-limiting untoward reaction.
Dalbavancin mechanism of action is identical with vancomycin and teicoplanin, it is suppressed that G+The biosynthesis of bacterial cell wall, is widely used as the medicine for the treatment of Skin and soft tissue infection. The inside and outside test of body shows, dalbavancin is for G+Bacterium, has antibacterial activity including Methicillin resistant Staph. aureus (MRSA), methicillin-sensitivity staphylococcus aureus (MSSA), coagulase negative staphylococcus (CoNS), streptococcus etc. To resistance to G+It is active that pathogen includes penicillin resistant and ceftriaxone streptococcus pneumoniae, the insensitive CoNS of teicoplanin, non-vanA type enterococcus; To G+Anaerobe is also active. Dalbavancin has the pharmacokinetics of uniqueness, can often weekly interval medication. At present, dalbavancin is treating the relevant Hematogenous infection of conduit and Skin and soft tissue infection achieved with good effect, and it has excellent antibacterial activity in vivo and safety, is desirable second generation of glycopeptide antibiotics. Its precursor A40926 Shi Youyeye village actinomyces (Nonomuraea)sp.ATCC39727 the natural glycopeptide antibiotics produced. A40926 can obtain dalbavancin after carrying out modifying for chemical structure. Food and drug administration (FDA) has been approved by dalbavancin listing on May 23rd, 2014.
Dalbavancin precursor A40926 is currently mainly produced by fermentable, and A40926 and derivant structure formula thereof are as follows:
。
Fermentation produces 5 key component: PA, PB, A, B0 and B1, and B0 and B1 is referred to as B component. In fermentation liquid, PA, PB are in separating purge process during long-time incubation in alkaline environment, can be converted into A, B. Wherein, B0 component is the main active component of A40926; it it is the key intermediate of synthesis dalbavancin; it is characterized in that on glycosamine, fatty acid chain is Fancol ID base; after the fatty acid from own cells film being carried out decomposed under the effect of acyltransferase in A40926 biosynthesis, it is principal element (the FactorsinfluencingcellfattyacidcompositionandA40926antib ioticcomplexproductionin causing this difference that formation acyl chain is connected on the amino of glycosamineNonomuraeasp.ATCC39727)。
Reporting less at present both at home and abroad in A40926 fermentation technology, the fermentating formula nutritional labeling of the VicuronPharmaceuticals drugmaker report of Italy is simple, and spawn activity is not strong, and fermentation unit is 128mg/L only.
Beltrametti etc. study discovery; Valine is the potential precursor of branch's acyl chain of B0 component; add Valine in the fermentation medium and can increase the ratio of B0 component in product, improve total output (the ValineInfluencesProductionandComplexCompositionofGlycope ptideAntibioticA40926inFermentationsof of A40926 simultaneouslyNonomuraeasp.ATCC39727. JAntibiot (Tokyo) .2004Jan; 57 (1): 37-44), but fermentation unit increase rate limited only have 220mg/L.
CN201010164616.4 discloses a kind of by adjusting carbon nitrogen source composition and proportioning in fermentation medium, the method of the fermentation parameters such as optimization culture temperature, pH, improving the fermentation yield of A40926, the fermentation unit of method disclosed in the patent A40926 may be up to 336mg/L.
CN103060405A discloses the fermentation technology stream during the fermentation of a kind of optimization and adds glucose, peptone and Valine, fermentation unit is up to 720mg/L, the method substantially increases the fermentation unit of A40926 to a certain extent, but still it is not strong to there is feed supplement specific aim, trivial operations, the problem that tunning yield is low, it is therefore desirable to exploitation improves the A40926 significant method of fermentation unit effect further.
Summary of the invention
It is an object of the invention to, for the deficiency that existing fermentation technology exists, it is provided that a kind of simple to operate, cost is low, is suitable for industrialized production, the fermentation technology of efficient dalbavancin precursor A40926.
The invention provides a kind of method producing dalbavancin precursor A40926, including, in fermentation medium, add 10-methyl undecanoic acid or its salt during the fermentation.
In the present invention, the method producing dalbavancin precursor A40926, including, during the fermentation to add 10-methyl undecanoic acid or its salt in fermentation medium in the way of stream adds.
In one embodiment, it is preferable that the method producing dalbavancin precursor A40926, including, during the fermentation to add 10-methyl undecanoic acid or its salt in fermentation medium in the way of stream adds.
Further, it is preferable that the method producing dalbavancin precursor A40926, including, after fermentation culture 24 ~ 48h, in every liter of fermentation liquid, add the methyl oleate solution of 10-methyl undecanoic acid to stream in fermentation tank with the flow velocity of 0.03 ~ 0.07ml/h, until fermentation ends. Generally, when, after fermentation 120h, when the concentration of dalbavancin precursor A40926 no longer increases, stopping fermentation, namely think fermentation ends.
Further, it is preferable that it is 40% ~ 60% (w/w) that described stream adds the concentration of the methyl oleate solution of 10-methyl undecanoic acid.
In another embodiment, it is preferable that the method producing dalbavancin precursor A40926, including, after fermentation culture 24 ~ 48h, in every liter of fermentation liquid, add 10-methylundecane acid salt solution with the flow velocity of 0.1 ~ 0.3ml/h to stream in fermentation tank, until fermentation ends. Generally, when, after fermentation 120h, when the concentration of dalbavancin precursor A40926 no longer increases, stopping fermentation, namely think fermentation ends.
Further, preferably, it is 5 ~ 15% (w/v) that described stream adds the concentration of 10-methylundecane acid salt solution, and described 10-methylundecane hydrochlorate is 10-methyl undecanoic acid sodium, 10-methyl undecanoic acid potassium, 10-methyl undecanoic acid ammonium or its mixture of any two or three.
In said method of the present invention, preferably, after fermentation culture 24 ~ 48h, when Biomass PMV reaches more than 20%, starting stream and add 10-methyl undecanoic acid or its salt, until fermentation ends, wherein said Biomass PMV is defined as: take the 10ml fermentation liquid centrifugal 15min that is placed in graduated centrifuge tube 3000rpm, pouring out supernatant volume is V, then PMV=(10-V)/10.
In said method, further, it is preferable that fermentation temperature is 24 ~ 28 DEG C, pressure is 0.04 ~ 0.06Mpa, and ventilation is 0.5 ~ 1.5VVM, and rotating speed is 100 ~ 250rpm.
In the present invention, described produce A40926 strain be described in the routine of this area can the strain of fermenting and producing A40926, it is preferably Ye Ye village actinomycetes, it is further preferred that described strain is Ye Ye village actinomyces actinomycetes ATCC39727 (Nonomuraea.sp.ATCC39727).
In the present invention, the method for described production dalbavancin precursor A40926, also include the step of seed culture, the strain seed producing A40926 is inoculated in seed culture medium, carries out seed culture. Described seed culture medium can use fluid medium commonly used in the art, the compound method of preferred described seed culture medium is as follows: glucose 10g/L, maltodextrin 25g/L, yeast extract 5g/L, soybean cake powder 20g/L, magnesium sulfate 1g/L, dipotassium hydrogen phosphate 1g/L, calcium carbonate 2g/L, PH7.0.
Prepare appropriate seed culture medium, after 120 DEG C of sterilizing 30min, be cooled to 26-30 DEG C, access the shake-flask seed in 48h kind age by the inoculum concentration of seed culture medium volume ratio 0.3-1%, then cultivate 48 ~ 72h for 26-30 DEG C.
In the present invention, the fermentation medium of described fermenting and producing dalbavancin precursor A40926 is the fermentation medium of the described strain use producing A40926 of this area routine, it is preferable that described fermentation medium compound method is as follows:
Glucose 10g/L, maltodextrin 25g/L, soluble starch 25g/L, yeast extract 5g/L, peptone 5g/L, soybean cake powder 30g/L, magnesium sulfate 0.5g/L, calcium carbonate 2g/L, pH7.0.
Prepare appropriate fermentation medium, it is cooled to 24 ~ 28 DEG C after 120 DEG C of sterilizing 30min, the trophosome inoculum in seed culture medium is accessed by the inoculum concentration of fermentation medium volume ratio 5 ~ 10%, sweat controls temperature at 24 ~ 28 DEG C, control pressure at 0.04 ~ 0.06Mpa, control ventilation at 0.5 ~ 1.5VVM, control rotating speed at 100 ~ 250rpm, dissolved oxygen electrode on-line monitoring, to guarantee that dissolved oxygen (assumes that the initial dissolved oxygen of fermentation tank is for 100%) more than 30%.
After fermentation culture 24 ~ 48h, when Biomass PMV (takes the 10ml fermentation liquid centrifugal 15min that is placed in graduated centrifuge tube 3000rpm, pouring out supernatant volume is V, then PMV=(10-V)/10) start stream when reaching more than 20% and add 10-methyl undecanoic acid or its salt, until fermentation ends. Generally, when, after fermentation 120h, when the concentration of dalbavancin precursor A40926 no longer increases, stopping fermentation.
Preferably, described feed process is add 40 ~ the methyl oleate solution of the 10-methyl undecanoic acid of 60% with the flow velocity of 0.03 ~ 0.07ml/h toward stream in fermentation tank in every liter of fermentation liquid, until fermentation ends.
Preferably, described feed process is add 5 ~ the 10-methylundecane acid salt solution of 15% with the flow velocity of 0.1 ~ 0.3ml/h toward stream in fermentation tank in every liter of fermentation liquid, until fermentation ends. Described 10-methylundecane hydrochlorate is 10-methyl undecanoic acid sodium, 10-methyl undecanoic acid potassium, 10-methyl undecanoic acid ammonium.
In the present invention, the compound method of the methyl oleate solution of described 10-methyl undecanoic acid is as follows: dissolved in in-tank mixing with methyl oleate by appropriate 10-methyl undecanoic acid, making 10-methyl undecanoic acid ratio in whole solution is 40 ~ 60% (w/w), 120 DEG C of sterilizing 30min, stand-by.
In the present invention, being formulated as follows of described 10-methylundecane acid salt solution: appropriate 10-methylundecane hydrochlorate is dissolved in water in tank, it is configured to the 10-methylundecane acid salt solution of 5 ~ 15% (w/v), 120 DEG C of sterilizing 30min, stand-by.
Adopting HPLC to detect the concentration of dalbavancin precursor A40926 in sweat, testing conditions is as follows:
Chromatographic column specification: 4.6mm*250mm*5 μm of C18 post, wavelength: 210nm, column temperature: 40 DEG C, flow velocity: 1ml/min, adopt gradient elution, mobile phase A phase: 0.02M potassium dihydrogen phosphate aqueous solution (W/V): acetonitrile=75:25 (V/V), Mobile phase B phase: 0.02M potassium dihydrogen phosphate aqueous solution (W/V): acetonitrile=62:38 (V/V)
| Time (min) | A phase | B phase |
| 0 | 100 | 0 |
| 29 | 0 | 100 |
| 31 | 100 | 0 |
| 36 | 100 | 0 |
Retention time: about 23min.
The present inventor is found surprisingly that, 10-methyl undecanoic acid can provide precursor for the biosynthesis of fatty acid chain on the glycosamine of dalbavancin precursor A40926 key component B0, to increasing the ratio of B0 component in product, the total output effect simultaneously improving A40926 is notable. But cell is had a degree of toxicity by this kind of precursor substance, excessive microorganism normal growth can be affected. It is thus desirable to by suitable flow acceleration feed supplement, reduce the suppression to microorganism while promoting fermentation unit to improve. Simultaneously 10-methyl undecanoic acid water solublity is poor, and methyl oleate as cosolvent or adds in a salt form in fermentation culture and is conducive to abundant mixing, it is ensured that the supply of precursor substance.
The method that the present invention improves significantly improves fermentation yield, improves more than 50%, reduce production cost, be suitable to industrialized production compared with the technique of current report.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is expanded on further. Should be understood that these embodiments are merely to illustrate the present invention and do not mean that and the present invention has any restriction. Agents useful for same of the present invention and raw material are commercially except specified otherwise.
Meeting on the basis of this area general knowledge, the optimum condition of the above-mentioned various technical characteristics of the present invention can obtain the preferred embodiments of the present invention by arbitrary composition.
In embodiment 1 sweat, stream adds the methyl oleate solution of 10-methyl undecanoic acid
500L seed tank is prepared 300L seed culture medium, after 120 DEG C of sterilizing 30min, is cooled to 28 DEG C, access the shake-flask seed in 48h kind age by the inoculum concentration of seed culture medium volume ratio 0.5%, then cultivate 72h for 28 DEG C.
5000L fermentation tank is prepared 3500L fermentation medium, it is cooled to 26 DEG C after 120 DEG C of sterilizing 30min, above-mentioned seed culture medium Middle nutrition body inoculum is accessed by the inoculum concentration of fermentation medium volume ratio 8%, sweat controls temperature at 24 ~ 28 DEG C, control pressure at 0.04 ~ 0.06Mpa, control ventilation at 0.5 ~ 1.5VVM, control rotating speed at 100 ~ 250rpm, dissolved oxygen electrode on-line monitoring, to guarantee that dissolved oxygen (assumes that the initial dissolved oxygen of fermentation tank is for 100%) more than 30%.
Fermentation 30h, PMV reaches 24%, start from the methyl oleate solution of the 10-methyl undecanoic acid adding 50% with the flow velocity of 0.05ml/h toward stream in fermentation tank in every liter of fermentation liquid, continuing fermentation, stop fermentation after 120h when fermentation unit no longer increases, pH to 11.5,50 DEG C of water-bath 1h adjusted by fermentation liquid, filtering, it is 1.46g/L that HPLC detects fermentation unit.
In embodiment 2 sweat, stream adds 10-methylundecane acid sodium solution
500L seed tank is prepared 350L seed culture medium, after 120 DEG C of sterilizing 30min, is cooled to 28 DEG C, access the shake-flask seed in 48h kind age by the inoculum concentration of seed culture medium volume ratio 0.8%, then cultivate 68h for 28 DEG C.
5000L fermentation tank is prepared 3500L fermentation medium, it is cooled to 27 DEG C after 120 DEG C of sterilizing 30min, above-mentioned seed culture medium Middle nutrition body inoculum is accessed by the inoculum concentration of fermentation medium volume ratio 10%, sweat controls temperature at 24 ~ 28 DEG C in sweat, control pressure at 0.04 ~ 0.06Mpa, control ventilation at 0.5 ~ 1.5VVM, control rotating speed at 100 ~ 250rpm, dissolved oxygen electrode on-line monitoring, to guarantee that dissolved oxygen (assumes that the initial dissolved oxygen of fermentation tank is for 100%) more than 30%.
Fermentation 40h, PMV reaches 25%, start from the 10-methylundecane acid sodium solution adding 10% with the flow velocity of 0.2ml/h toward feed supplement stream in fermentation tank in every liter of fermentation liquid, continuing fermentation, stop fermentation after 120h when fermentation unit no longer increases, PH to 11.5,50 DEG C of water-bath 1h adjusted by fermentation liquid, filtering, it is 1.54g/L that HPLC detects fermentation unit.
In embodiment 3 sweat, stream adds 10-methylundecane acid ammonium solution
1T seed tank is prepared 600L seed culture medium, after 120 DEG C of sterilizing 30min, is cooled to 28 DEG C, access the shake-flask seed in 48h kind age by the inoculum concentration of seed culture medium volume ratio 0.3%, then cultivate 72h for 28 DEG C.
20T fermentation tank is prepared 10000L fermentation medium, it is cooled to 26 DEG C after 120 DEG C of sterilizing 30min, above-mentioned seed culture medium Middle nutrition body inoculum is accessed by the inoculum concentration of fermentation medium volume ratio 5%, sweat controls temperature at 24 ~ 28 DEG C in sweat, control pressure at 0.04 ~ 0.06Mpa, control ventilation at 0.5 ~ 1.5VVM, control rotating speed at 100 ~ 250rpm, dissolved oxygen electrode on-line monitoring, to guarantee that dissolved oxygen (assumes that the initial dissolved oxygen of fermentation tank is for 100%) more than 30%.
Fermentation 48h, PMV reaches 21%, start from the 10-methylundecane acid ammonium solution adding 15% with the flow velocity of 0.15ml/h toward feed supplement stream in fermentation tank in every liter of fermentation liquid, continuing fermentation, stop fermentation after 120h when fermentation unit no longer increases, PH to 11.5,50 DEG C of water-bath 1h adjusted by fermentation liquid, filtering, it is 1.49g/L that HPLC detects fermentation unit.
In embodiment 4 sweat, stream adds 10-methyl undecanoic acid potassium solution
1T seed tank is prepared 700L seed culture medium, after 120 DEG C of sterilizing 30min, is cooled to 28 DEG C, access the shake-flask seed in 48h kind age by the inoculum concentration of seed culture medium volume ratio 0.3%, then cultivate 72h for 28 DEG C.
20T fermentation tank is prepared 10000L fermentation medium, it is cooled to 26 DEG C after 120 DEG C of sterilizing 30min, above-mentioned seed culture medium Middle nutrition body inoculum is accessed by the inoculum concentration of fermentation medium volume ratio 6%, sweat controls temperature at 24 ~ 28 DEG C in sweat, control pressure at 0.04 ~ 0.06Mpa, control ventilation at 0.5 ~ 1.5VVM, control rotating speed at 100 ~ 250rpm, dissolved oxygen electrode on-line monitoring, to guarantee that dissolved oxygen (assumes that the initial dissolved oxygen of fermentation tank is for 100%) more than 30%.
Fermentation 48h, PMV reaches 23%, start from the 10-methyl undecanoic acid potassium solution adding 15% with the flow velocity of 0.13ml/h toward feed supplement stream in fermentation tank in every liter of fermentation liquid, continuing fermentation, stop fermentation after 120h when fermentation unit no longer increases, PH to 11.5,50 DEG C of water-bath 1h adjusted by fermentation liquid, filtering, it is 1.39g/L that HPLC detects fermentation unit.
In embodiment 5 sweat, stream adds the methyl oleate solution of 10-methyl undecanoic acid
500L seed tank is prepared 300L seed culture medium, after 120 DEG C of sterilizing 30min, is cooled to 28 DEG C, access the shake-flask seed in 48h kind age by the inoculum concentration of seed culture medium volume ratio 0.5%, then cultivate 72h for 28 DEG C.
5000L fermentation tank is prepared 3500L fermentation medium, it is cooled to 26 DEG C after 120 DEG C of sterilizing 30min, above-mentioned seed culture medium Middle nutrition body inoculum is accessed by the inoculum concentration of fermentation medium volume ratio 8%, sweat controls temperature at 24 ~ 28 DEG C, control pressure at 0.04 ~ 0.06Mpa, control ventilation at 0.5 ~ 1.5VVM, control rotating speed at 100 ~ 250rpm, dissolved oxygen electrode on-line monitoring, to guarantee that dissolved oxygen (assumes that the initial dissolved oxygen of fermentation tank is for 100%) more than 30%.
Fermentation 24h, PMV reaches 21%, start from the methyl oleate solution of the 10-methyl undecanoic acid adding 40% with the flow velocity of 0.03ml/h toward stream in fermentation tank in every liter of fermentation liquid, continuing fermentation, stop fermentation after 120h when fermentation unit no longer increases, pH to 11.5,50 DEG C of water-bath 1h adjusted by fermentation liquid, filtering, it is 1.42g/L that HPLC detects fermentation unit.
Claims (9)
1. the method producing dalbavancin precursor A40926, it is characterised in that add 10-methyl undecanoic acid or its salt during the fermentation in fermentation medium.
2. method according to claim 1, it is characterised in that during the fermentation to add 10-methyl undecanoic acid or its salt in fermentation medium in the way of stream adds.
3. method according to claim 2, it is characterised in that after fermentation culture 24 ~ 48h, add the methyl oleate solution of 10-methyl undecanoic acid in every liter of fermentation liquid to stream in fermentation tank with the flow velocity of 0.03 ~ 0.07ml/h, until fermentation ends.
4. method according to claim 3, it is characterised in that the concentration of the methyl oleate solution of the 10-methyl undecanoic acid that described stream adds is 40% ~ 60% (w/w).
5. method according to claim 2, it is characterised in that after fermentation culture 24 ~ 48h, add the aqueous solution of 10-methylundecane hydrochlorate in every liter of fermentation liquid to stream in fermentation tank with the flow velocity of 0.1 ~ 0.3ml/h, until fermentation ends.
6. method according to claim 5, it is characterized in that, it is 5 ~ 15% (w/v) that described stream adds the concentration of 10-methylundecane acid salt solution, and described 10-methylundecane hydrochlorate is 10-methyl undecanoic acid sodium, 10-methyl undecanoic acid potassium, 10-methyl undecanoic acid ammonium or its mixture of any two or three.
7. according to the arbitrary described method of claim 1 ~ 6, it is characterized in that, after fermentation culture 24 ~ 48h, start stream when Biomass PMV reaches more than 20% and add 10-methyl undecanoic acid or its salt, until fermentation ends, wherein said Biomass PMV is defined as: taking the 10ml fermentation liquid centrifugal 15min that is placed in graduated centrifuge tube 3000rpm, pouring out supernatant volume is V, then PMV=(10-V)/10.
8. according to the arbitrary described method of claim 1 ~ 6, it is characterised in that fermentation temperature is 24 ~ 28 DEG C, pressure is 0.04 ~ 0.06Mpa, and ventilation is 0.5 ~ 1.5VVM, and rotating speed is 100 ~ 250rpm.
9. according to the arbitrary described method of claim 1 ~ 6, it is characterised in that the strain that fermentation uses is Ye Ye village actinomycetes.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110105435A (en) * | 2019-05-08 | 2019-08-09 | 东莞东阳光药物研发有限公司 | A kind of fermentation medium and fermentation process producing A40926 |
| CN110551786A (en) * | 2019-09-12 | 2019-12-10 | 浙江海正药业股份有限公司 | Fermentation medium for increasing yield of A40926B 0 and method thereof |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN85107903A (en) * | 1984-10-11 | 1987-05-06 | 格鲁波莱佩蒂特公司 | Produce the method for antibiotic A40926 complex and pure factors PA.PB.A.B. and B0 |
| EP0836619A1 (en) * | 1995-07-05 | 1998-04-22 | GRUPPO LEPETIT S.p.A. | Purification of dalbaheptide antibiotics by isoelectric focusing |
| EP1005356A1 (en) * | 1998-06-08 | 2000-06-07 | Advanced Medicine, Inc. | Novel antibacterial agents |
| CN1732263A (en) * | 2002-10-23 | 2006-02-08 | 维柯龙药品公司 | Genes and proteins for the biosynthesis of the glycopeptide antibiotic A40926 |
| CN1741810A (en) * | 2002-08-30 | 2006-03-01 | 鲁汶天主教大学研究开发部 | Glycopeptide antibiotic derivatives |
| CN101851277A (en) * | 2009-03-12 | 2010-10-06 | 成都雅途生物技术有限公司 | Preparation method of Dalbavancin key intermediate A40926 BO component by purification |
| WO2011019839A2 (en) * | 2009-08-12 | 2011-02-17 | The Medicines Company | Glycopeptide and lipoglycopeptide antibiotics with improved solubility |
| CN102234675A (en) * | 2010-04-29 | 2011-11-09 | 上海医药工业研究院 | Fermentation medium and fermentation method of producing A40926 with Nonomuraea.sp by fermentation |
| CN103060405A (en) * | 2011-10-21 | 2013-04-24 | 上海医药工业研究院 | Fermentation technique of A40926 |
-
2015
- 2015-05-05 CN CN201510221758.2A patent/CN105671110B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN85107903A (en) * | 1984-10-11 | 1987-05-06 | 格鲁波莱佩蒂特公司 | Produce the method for antibiotic A40926 complex and pure factors PA.PB.A.B. and B0 |
| EP0836619A1 (en) * | 1995-07-05 | 1998-04-22 | GRUPPO LEPETIT S.p.A. | Purification of dalbaheptide antibiotics by isoelectric focusing |
| EP1005356A1 (en) * | 1998-06-08 | 2000-06-07 | Advanced Medicine, Inc. | Novel antibacterial agents |
| CN1741810A (en) * | 2002-08-30 | 2006-03-01 | 鲁汶天主教大学研究开发部 | Glycopeptide antibiotic derivatives |
| CN1732263A (en) * | 2002-10-23 | 2006-02-08 | 维柯龙药品公司 | Genes and proteins for the biosynthesis of the glycopeptide antibiotic A40926 |
| CN101851277A (en) * | 2009-03-12 | 2010-10-06 | 成都雅途生物技术有限公司 | Preparation method of Dalbavancin key intermediate A40926 BO component by purification |
| WO2011019839A2 (en) * | 2009-08-12 | 2011-02-17 | The Medicines Company | Glycopeptide and lipoglycopeptide antibiotics with improved solubility |
| CN102234675A (en) * | 2010-04-29 | 2011-11-09 | 上海医药工业研究院 | Fermentation medium and fermentation method of producing A40926 with Nonomuraea.sp by fermentation |
| CN103060405A (en) * | 2011-10-21 | 2013-04-24 | 上海医药工业研究院 | Fermentation technique of A40926 |
Non-Patent Citations (2)
| Title |
|---|
| S JOVETIC等: "Factors influencing cell fatty acid composition and A40926 antibiotic complex production in Nonomuraea sp. ATCC 39727", 《JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECH》 * |
| 沈晓放等: "半合成糖肽类抗生素达巴万星前体 A40926 的生物合成", 《中国医药工业杂志》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110105435A (en) * | 2019-05-08 | 2019-08-09 | 东莞东阳光药物研发有限公司 | A kind of fermentation medium and fermentation process producing A40926 |
| CN110105435B (en) * | 2019-05-08 | 2023-12-08 | 宜昌东阳光生化制药有限公司 | Fermentation medium and fermentation method for producing A40926 |
| CN110551786A (en) * | 2019-09-12 | 2019-12-10 | 浙江海正药业股份有限公司 | Fermentation medium for increasing yield of A40926B 0 and method thereof |
| WO2021047431A1 (en) * | 2019-09-12 | 2021-03-18 | 浙江海正药业股份有限公司 | Fermentation culture medium and fermentation method capable of increasing yield of a40926 b0 |
| CN110551786B (en) * | 2019-09-12 | 2021-12-07 | 浙江海正药业股份有限公司 | Fermentation medium for increasing yield of A40926B 0 and method thereof |
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