CN102993251A - Method for purifying tiacumicin B by high performance liquid chromatography - Google Patents
Method for purifying tiacumicin B by high performance liquid chromatography Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 43
- 238000004128 high performance liquid chromatography Methods 0.000 title abstract description 8
- 229960000628 fidaxomicin Drugs 0.000 title abstract description 5
- ZVGNESXIJDCBKN-UUEYKCAUSA-N fidaxomicin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@H]([C@H]1O)OC)OCC\1=C/C=C/C[C@H](O)/C(C)=C/[C@@H]([C@H](/C(C)=C/C(/C)=C/C[C@H](OC/1=O)[C@@H](C)O)O[C@H]1[C@H]([C@@H](O)[C@H](OC(=O)C(C)C)C(C)(C)O1)O)CC)C(=O)C1=C(O)C(Cl)=C(O)C(Cl)=C1CC ZVGNESXIJDCBKN-UUEYKCAUSA-N 0.000 title abstract description 5
- 238000000746 purification Methods 0.000 claims abstract description 22
- 239000000945 filler Substances 0.000 claims abstract description 11
- 229920000642 polymer Polymers 0.000 claims abstract description 11
- 238000004587 chromatography analysis Methods 0.000 claims abstract description 5
- 238000004440 column chromatography Methods 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 121
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 26
- 239000007864 aqueous solution Substances 0.000 claims description 20
- 239000012071 phase Substances 0.000 claims description 20
- 239000000243 solution Substances 0.000 claims description 16
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 13
- 235000019253 formic acid Nutrition 0.000 claims description 13
- 239000007791 liquid phase Substances 0.000 claims description 12
- 238000011068 loading method Methods 0.000 claims description 10
- 239000012043 crude product Substances 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 230000005526 G1 to G0 transition Effects 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 238000010926 purge Methods 0.000 claims description 2
- 239000012488 sample solution Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 11
- 238000000926 separation method Methods 0.000 abstract description 9
- 239000012535 impurity Substances 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract description 6
- 238000011084 recovery Methods 0.000 abstract description 5
- 239000004005 microsphere Substances 0.000 abstract 1
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- 238000011010 flushing procedure Methods 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Natural products C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- -1 chlorins compound Chemical class 0.000 description 4
- 229920001577 copolymer Polymers 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 101100313763 Arabidopsis thaliana TIM22-2 gene Proteins 0.000 description 2
- 241000193163 Clostridioides difficile Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000005374 membrane filtration Methods 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 241000186361 Actinobacteria <class> Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241001404671 Dactylosporangium aurantiacum subsp. hamdenensis Species 0.000 description 1
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 229930187202 Tiacumicin Natural products 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for purifying tiacumicin B by high performance liquid chromatography, wherein in the method, Uni30BPC monodisperse polymer microspheres are used as fillers for performing column chromatography in a purification and chromatography column. The invention provides a method which is better in separation effect for tiacumicin B, wherein a novel medium which is high in separation factor and column efficiency is adopted, thus overcoming the shortages of low separation factor and bad column efficiency existing in the prior art, having a good removal effect for various impurities in tiacumicin B, and being high in preparation purity and recovery rate.
Description
Technical field
The present invention relates to a kind of purification process, particularly a kind of method of high-efficient liquid phase chromatogram purification TCM B.
Background technology
It is the general name that is referred to a series of 18 yuan of ring macrolide antibiotics that sporangiocyst bacterium Dactylosporangium aurantiacumsubsp.hamdenensis NRRL 18085 produces by actinomycetes that platform colludes mycin (tiacumicins).Platform colludes the activity that mycin has anti-various gram positive bacteriums, particularly has obvious anti-microbial activity for clostridium difficile and tubercule bacillus, also has simultaneously anti-tumor activity.Research finds that platform colludes that tiacumicn B is best active ingredient in the mycin, has two deoxidation glycosyls and an aromatic nucleus side chain, and C-18 is the R-hydroxyl, and clostridium difficile is had lower minimum inhibition concentration value.TCM B (Tiacumicin B) refers to have the molecule of lower array structure:
TCM B is very strong because of its hydrophobicity, and is almost insoluble in water, so generally adopt the method preparation of reverse-phase chromatography.
Chinese patent 102219815A discloses and has a kind ofly prepared the method that platform colludes mould chlorins compound from the sporangiocyst bacterium, and the method comprises combining with gel Sephadex LH-20 and the anti-phase middle pressure chromatography of silica gel YMCGEL ODS-A and thin layer chromatography to be isolated the low platform of purity and collude mould chlorins compound from sporangiocyst bacterium tunning.
Chinese patent 102030791 A disclose the preparation method that four kinds of platforms collude mould chlorins compound, the method adopts macroporous adsorbent resin XAD16 to extract crude extract from fermented liquid, then in conjunction with extraction and the concentrated crude product that obtains, these crude product purity are lower, also will pass through purification on normal-phase silica gel chromatography, gel filtration chromatography and anti-phase middle pressure chromatogram and could obtain respectively four kinds of platforms and collude mould chlorins compound.
Chinese patent 1688707A discloses a kind of preparation and purification process that colludes mycin, and the method adopts inverted medium pressure liquid chromatography method, take silica gel keys C18 as solid phase, with MeCN/H
2O/AcOH is moving phase, the product in the collection liquid is obtained the product of purity 93% and the rate of recovery 30% behind extraction and recrystallization.
In these prior aries, all there is the deficiency of and post heterodyne low because of the separation factor of purification media, and makes the purity of product not reach requirements, problem that yield is lower, separating effect remains further raising.
Summary of the invention
The purpose of this invention is to provide a kind of product purity height, high, the better TCM B purification process of separating effect of the rate of recovery.
For achieving the above object, technical scheme of the present invention is: a kind of method with the high-efficient liquid phase chromatogram purification TCM B, described method adopts Uni30BPC monodisperse polymer microballoon to carry out column chromatography as filler in the purifying chromatography column.This Uni30BPC monodisperse polymer microballoon by Suzhou Nano-Micro Bio-technology Co., Ltd. design, make and produce, have the TCM B separation factor high, the characteristics that post is imitated, and ability strong acid, highly basic, anti-certain pressure and have uniform particle diameter.Uni30BPC monodisperse polymer microballoon is packed in the chromatography column as stationary phase as filler, and aqueous formic acid and organic solvent are as moving phase, and filler is used first the moving phase balance through after the pre-treatment.
Preferably, described method is with the stationary phase of Uni30BPC monodisperse polymer microballoon as chromatographic column, will contain the sample solution loading of TCM B on chromatographic column, is adsorbed on TCM B on the filler with the moving phase wash-out.
Preferably, the pressure of described method in dress post and purge process is all less than 4 Mpa.
Preferably, described TCM B crude product is with 40%～80% methyl alcohol or aqueous ethanolic solution dissolving.
Preferably, described moving phase is the aqueous solution that contains organic solvent, and wherein organic solvent is methyl alcohol or acetonitrile, and the aqueous solution is the aqueous solution that contains 0.1% formic acid or acetic acid.
Preferably, the described TCM B that is adsorbed on the filler with the moving phase wash-out is to wash a column volume with 10%～30% acetonitrile or methanol aqueous solution first, and then washes 8～12 column volumes with 40%～60% acetonitrile or methanol aqueous solution, namely washes assorted; Wherein the aqueous solution is the aqueous solution that contains 0.1% formic acid.
Preferably, the described TCM B that is adsorbed on the filler with the moving phase wash-out is to wash a column volume with 10%～30% acetonitrile solution first, and then washes 8～12 column volumes with 40%～60% acetonitrile solution, namely washes assorted; Wherein the aqueous solution is the aqueous solution that contains 0.1% formic acid.
Preferably, the volume ratio of described method used acetonitrile solution in washing assorted process is acetonitrile: water=15～25:75～85.
Preferably, the volume ratio of described method used acetonitrile solution in washing assorted process is acetonitrile: water=45～55:45～55.
The invention provides the better TCM B purification process of a kind of separating effect, present method adopts the novel medium that a kind of separation factor is high, the post effect is high, overcome the deficiency of the low and post heterodyne of the separation factor that exists in the prior art, various impurity in the TCM B there is preferably removal effect, the purity of preparation is high, and the rate of recovery that obtains is high.
Description of drawings
Figure l is the stereoscan photograph of the Uni30BPC polymer microballoon of embodiment one use.
Fig. 2 is the HPLC chromatogram of the crude product before embodiment one purifies.
Fig. 3 is the HPLC chromatogram according to embodiment one, two, three, four the method TCM B after with the Uni30BPC purifying.
Fig. 4 is the HPLC chromatogram according to embodiment five, six the method TCM B after with the HP20SS purifying.
Embodiment
Below in conjunction with specific embodiment technical scheme of the present invention is further described, but the present invention is not limited to these embodiment.
The purifying of TCM B: the glass column that adopts 15 * 310mm, Uni30BPC resin (pyrrolidone and styrene copolymer spherolite footpath 30 ± 1.5um, Microbial Technics Ltd is received in Suzhou) as chromatographic stuffing, the dress column volume is 55ml, first with 2 CV(column volumes of 60% acetonitrile solution flushing), then use 2 CV of 20% acetonitrile balance.Moving phase: A:0.1% aqueous formic acid; B: acetonitrile.TCM B crude product (purity 78%) dissolves with 60% methanol aqueous solution, uses the 0.45um membrane filtration.Concentration 8mg/ml, loading volume 45.8ml, loading flow velocity 5ml/min, the 20%B prewashing of 1CV, then the 50%B wash-out of 8 CV.Fractional Collections, leading portion are collected liquid purity 85.6%(not to be had rear assorted substantially), account for applied sample amount proportion 20.9%; Stage casing purity accounts for applied sample amount proportion 49.85% 90.72%; Back segment is collected liquid purity 79.2%(not to be had front assorted substantially), account for applied sample amount proportion 27.9%.
Fig. 1 is the stereoscan photograph of the Uni30BPC polymer microballoon that uses of embodiment one, as seen from the figure the particle diameter of microballoon homogeneous very.
Fig. 2 is the HPLC chromatogram of the crude product before embodiment one purifies, and the retention time of TCM B is about 14.5 minutes, and as seen a lot of assorted peaks are arranged from color atlas, illustrates that crude product contains a lot of impurity.
Embodiment 2,
The purifying of TCM B: the glass column that adopts 15 * 310mm, Uni30BPC resin (material pyrrolidone and styrene copolymer spherolite footpath 30 ± 1.5um, Microbial Technics Ltd is received in Suzhou) as chromatographic stuffing, the dress column volume is 55ml, with 2 CV of 60% acetonitrile solution flushing, then use 2 CV of 20% acetonitrile balance first.Moving phase: A 0.1% aqueous formic acid; The B acetonitrile.The leading portion TCM B of collecting, 5 batches of mixed rear concentrating under reduced pressure make acetonitrile concentration be lower than 35%.Direct loading, flow velocity 5ml/min, the 20%B prewashing of 1CV, then the 45%B wash-out of 8 CV.It is 89.82% that Fractional Collections, purity reach 98% yield.
Embodiment 3,
The purifying of TCM B: the glass column that adopts 15 * 310mm, Uni30BPC resin (material pyrrolidone and styrene copolymer spherolite footpath 30 ± 1.5um, Microbial Technics Ltd is received in Suzhou) as chromatographic stuffing, the dress column volume is 55ml, with 2 CV of 60% acetonitrile solution flushing, then use 2 CV of 20% acetonitrile balance first.Moving phase: A 0.1% aqueous formic acid; The B acetonitrile.The stage casing TCM B of collecting, 2 batches of mixed rear concentrating under reduced pressure make acetonitrile concentration be lower than 35%.Direct loading, flow velocity 5ml/min, the 20%B prewashing of 1CV, then the 50%B wash-out of 8 CV.It is 36.46% that Fractional Collections, purity reach 98% yield.
Embodiment 4,
The purifying of TCM B: the glass column that adopts 15 * 310mm, Uni30BPC resin (material pyrrolidone and styrene copolymer spherolite footpath 30 ± 1.5um, Microbial Technics Ltd is received in Suzhou) as chromatographic stuffing, the dress column volume is 55ml, with 2 CV of 60% acetonitrile solution flushing, then use 2 CV of 20% acetonitrile balance first.Moving phase: A 0.1% aqueous formic acid; The B acetonitrile.The leading portion TCM B of collecting, 4 batches of mixed rear concentrating under reduced pressure make acetonitrile concentration be lower than 35%.Direct loading, flow velocity 5ml/min, the 20%B prewashing of 1CV, then the 55%B wash-out of 8 CV.It is 81.02% that Fractional Collections, purity reach 98% yield.
Fig. 3 is that the retention time of TCM B is about 14.5 minutes according to the HPLC chromatogram of embodiment one, two, three, four the method TCM B after with the Uni30BPC purifying.TCM B purity after the visible purification of color atlas is very high, and impurity seldom.
Embodiment 5,
The purifying of TCM B: adopt the glass column of 15 * 310mm, the HP20SS resin (be that the HP20 direct polymerization becomes the small grain size product, particle diameter 75um
~150um, Mitsubishi Chemical) as chromatographic stuffing, dress column volume 55ml with 2 CV of 60% acetonitrile solution flushing, then uses 2 CV of 20% acetonitrile balance first.Moving phase: A 0.1% aqueous formic acid; The B acetonitrile.TCM B crude product (purity 78%) dissolves with 60% methanol aqueous solution, uses the 0.45um membrane filtration.Concentration 8mg/ml, loading volume 45.8ml, loading flow velocity 5ml/min, the 20%B prewashing of 1CV, then the 50%B wash-out of 12 CV.Collect liquid after testing, purity is 25.6% greater than 90% yield.
Embodiment 6,
The purifying of TCM B: adopt the glass column of 15 * 310mm, the HP20SS resin (be that the HP20 direct polymerization becomes the small grain size product, particle diameter 75um
~150um, Mitsubishi Chemical) as chromatographic stuffing, dress column volume 55ml with 2 CV of 60% acetonitrile solution flushing, then uses 2 CV of 20% acetonitrile balance first.Moving phase: A 0.1% aqueous formic acid; The B acetonitrile.4 batches of mixed rear concentrating under reduced pressure make acetonitrile concentration be lower than 35%.Direct loading, flow velocity 5ml/min, the 20%B prewashing of 1CV, then the 50%B wash-out of 12 CV.Fractional Collections, purity does not reach 98%.Be 21% at the yield more than 95%.
Fig. 4 is that the retention time of TCM B is about 11.2 minutes according to the HPLC chromatogram of embodiment five, six the method TCM B after with the HP20SS purifying, and the TCM B purity from color atlas after visible the purification is very not high, still has impurity to exist.
With embodiment one, two, three, four and embodiment five, six result and performance compare.
Each embodiment performance perameter of table one and result are relatively
From relatively can finding out of table 1, the Uni30BPC polymer microballoon has very uniformly particle diameter, and other microballoon is then not of uniform size.Use the Uni30BPC polymer microballoon as the stationary phase of chromatographic column, use elutriant still less, but have better pure rate and yield simultaneously.
The invention provides the better TCM B purification process of a kind of separating effect, adopt the novel medium that a kind of separation factor is high, the post effect is high, overcome the deficiency of the low and post heterodyne of the separation factor that exists in the prior art, various impurity in the TCM B there is preferably removal effect, the purity of preparation is high, and the rate of recovery that obtains is high.
Above-described only is preferred implementation of the present invention, should be pointed out that for the person of ordinary skill of the art, under the prerequisite that does not break away from the invention design, can also make some distortion and improvement, and these all belong to protection scope of the present invention.
Claims (9)
1. the method with the high-efficient liquid phase chromatogram purification TCM B is characterized in that, described method adopts Uni30BPC monodisperse polymer microballoon to carry out column chromatography as filler in the purifying chromatography column.
2. the method with the high-efficient liquid phase chromatogram purification TCM B as claimed in claim 1, it is characterized in that, described method is with the stationary phase of Uni30BPC monodisperse polymer microballoon as chromatographic column, to contain again the sample solution loading of TCM B on chromatographic column, be adsorbed on TCM B on the filler with the moving phase wash-out.
3. the method with the high-efficient liquid phase chromatogram purification TCM B as claimed in claim 1 is characterized in that, the pressure of described method in dress post and purge process is all less than 4 Mpa.
4. the method with the high-efficient liquid phase chromatogram purification TCM B as claimed in claim 1 is characterized in that, described TCM B crude product dissolves with 40%～80% methyl alcohol or aqueous ethanolic solution.
5. the method with the high-efficient liquid phase chromatogram purification TCM B as claimed in claim 2 is characterized in that described moving phase is the aqueous solution that contains organic solvent, and wherein organic solvent is methyl alcohol or acetonitrile, and the aqueous solution is the aqueous solution that contains 0.1% formic acid or acetic acid.
6. the method with the high-efficient liquid phase chromatogram purification TCM B as claimed in claim 2, it is characterized in that, the described TCM B that is adsorbed on the filler with the moving phase wash-out is to wash a column volume with 10%～30% acetonitrile or methanol aqueous solution first, and then wash 8～12 column volumes with 40%～60% acetonitrile or methanol aqueous solution, namely wash assorted; Wherein the aqueous solution is the aqueous solution that contains 0.1% formic acid.
7. the method with the high-efficient liquid phase chromatogram purification TCM B as claimed in claim 6, it is characterized in that, the described TCM B that is adsorbed on the filler with the moving phase wash-out is to wash a column volume with 10%～30% acetonitrile solution first, and then wash 8～12 column volumes with 40%～60% acetonitrile solution, namely wash assorted; Wherein the aqueous solution is the aqueous solution that contains 0.1% formic acid.
8. the method with the high-efficient liquid phase chromatogram purification TCM B as claimed in claim 7 is characterized in that, the volume ratio of described method used acetonitrile solution in washing assorted process is acetonitrile: water=15～25:75～85.
9. the method with the high-efficient liquid phase chromatogram purification TCM B as claimed in claim 8 is characterized in that, the volume ratio of described method used acetonitrile solution in washing assorted process is acetonitrile: water=45～55:45～55.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104098637A (en) * | 2014-07-09 | 2014-10-15 | 浙江海正药业股份有限公司 | Method for purifying fidaxomicin |
| CN104418925A (en) * | 2013-09-05 | 2015-03-18 | 重庆乾泰生物医药有限公司 | Method for preparing high-purity fidaxomicin |
| CN104513286A (en) * | 2013-09-27 | 2015-04-15 | 博瑞生物医药技术(苏州)有限公司 | Method for separating and purifying fidaxomicin |
| CN104846043A (en) * | 2014-02-17 | 2015-08-19 | 上海医药工业研究院 | Process for separating and purifying fidaxomicin from fermentation broth |
| CN107236686B (en) * | 2017-06-21 | 2019-10-15 | 杭州华东医药集团新药研究院有限公司 | A kind of cyst fungus citrus finger and its application in regulating the microbial metabolite fidaxomicin |
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| CN104418925B (en) * | 2013-09-05 | 2018-09-28 | 重庆乾泰生物医药有限公司 | A method of preparing high-purity fidaxomicin |
| CN104418925A (en) * | 2013-09-05 | 2015-03-18 | 重庆乾泰生物医药有限公司 | Method for preparing high-purity fidaxomicin |
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| CN104513286A (en) * | 2013-09-27 | 2015-04-15 | 博瑞生物医药技术(苏州)有限公司 | Method for separating and purifying fidaxomicin |
| CN104846043A (en) * | 2014-02-17 | 2015-08-19 | 上海医药工业研究院 | Process for separating and purifying fidaxomicin from fermentation broth |
| CN104846043B (en) * | 2014-02-17 | 2018-06-01 | 上海医药工业研究院 | A kind of technique for being separated from zymotic fluid and purifying feldamycin |
| WO2016004848A1 (en) * | 2014-07-09 | 2016-01-14 | 浙江海正药业股份有限公司 | Fidaxomicin purification method |
| CN104098637B (en) * | 2014-07-09 | 2017-01-04 | 浙江海正药业股份有限公司 | A kind of method of purification feldamycin |
| CN104098637A (en) * | 2014-07-09 | 2014-10-15 | 浙江海正药业股份有限公司 | Method for purifying fidaxomicin |
| US10316052B2 (en) | 2014-07-09 | 2019-06-11 | Zhejiang Hisun Pharmaceutical Co., Ltd. | Fidaxomicin purification method |
| CN107236686B (en) * | 2017-06-21 | 2019-10-15 | 杭州华东医药集团新药研究院有限公司 | A kind of cyst fungus citrus finger and its application in regulating the microbial metabolite fidaxomicin |
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