Mingzu Yang, Bo Xu
Daim ntawv thov R&D Center
Taw qhia
Cov tshuaj tua kab mob yog ib chav kawm ntawm cov metabolites thib ob uas tsim los ntawm cov kab mob (xws li cov kab mob, cov kab mob fungi, actinomycetes) lossis cov tshuaj sib xws uas yog cov tshuaj sib xyaw ua ke lossis semi-synthesized.Cov tshuaj tua kab mob tuaj yeem cuam tshuam kev loj hlob thiab kev ciaj sia ntawm lwm cov kab mob.Thawj cov tshuaj tua kab mob tau tshawb pom los ntawm tib neeg, penicillin, tau tshawb pom los ntawm British microbiologist Alexander Fleming hauv xyoo 1928. Nws tau pom tias cov kab mob nyob ib puag ncig ntawm cov pwm tuaj yeem tsis tuaj yeem loj hlob hauv cov kab lis kev cai staphylococcus tais uas muaj kab mob pwm.Nws tau tshaj tawm tias cov pwm yuav tsum tso cov tshuaj tua kab mob, uas nws hu ua penicillin hauv xyoo 1928. Txawm li cas los xij, cov khoom xyaw nquag tsis huv thaum lub sijhawm ntawd.Xyoo 1939, Ernst Chain thiab Howard Florey ntawm Oxford University tau txiav txim siab los tsim cov tshuaj uas tuaj yeem kho cov kab mob.Tom qab hu rau Fleming kom tau txais cov kab mob, lawv tau ua tiav cov txiaj ntsig thiab ua kom huv penicillin los ntawm cov kab mob.Rau lawv txoj kev vam meej ntawm penicillin ua cov tshuaj kho mob, Fleming, Chain thiab Florey tau qhia txog 1945 Nobel nqi zog hauv Tshuaj.
Cov tshuaj tua kab mob yog siv los ua cov tshuaj tua kab mob los kho lossis tiv thaiv kab mob.Muaj ntau ntau hom tshuaj tua kab mob uas siv los ua cov tshuaj tua kab mob: β-lactam tshuaj tua kab mob (xws li penicillin, cephalosporin, thiab lwm yam), cov tshuaj tua kab mob aminoglycoside, tshuaj tua kab mob macrolide, tshuaj tua kab mob tetracycline, chloramphenicol (tag nrho cov tshuaj tua kab mob hluavtaws), thiab lwm yam. biological fermentation, semi-synthesis thiab tag nrho cov synthesis.Cov tshuaj tua kab mob uas tsim los ntawm cov tshuaj lom neeg fermentation yuav tsum tau hloov kho los ntawm cov txheej txheem tshuaj vim muaj tshuaj lom neeg ruaj khov, muaj kev phiv tshuaj lom, tshuaj tua kab mob thiab lwm yam teeb meem.Tom qab kev hloov kho tshuaj, cov tshuaj tua kab mob tuaj yeem ua kom muaj kev ruaj ntseg, txo cov kev mob tshwm sim, txo cov kab mob tua kab mob, txo cov tshuaj tiv thaiv, txhim kho bioavailability, thiab yog li txhim kho cov nyhuv ntawm kev kho tshuaj.Yog li ntawd, cov tshuaj tua kab mob semi-synthetic tam sim no yog cov kev taw qhia nrov tshaj plaws hauv kev tsim cov tshuaj tua kab mob.
Hauv kev tsim cov tshuaj tua kab mob semi-synthetic, cov tshuaj tua kab mob muaj cov yam ntxwv ntawm cov purity tsawg, ntau ntawm cov khoom lag luam thiab cov khoom siv nyuaj vim lawv tau muab los ntawm cov khoom siv microbial fermentation.Hauv qhov no, kev tshuaj xyuas thiab tswj cov impurities hauv cov tshuaj tua kab mob semi-synthetic yog qhov tseem ceeb tshwj xeeb.Txhawm rau txhawm rau txheeb xyuas thiab ua tus cwj pwm tsis zoo, nws yog ib qho tsim nyog kom tau txais ib qho txaus ntawm impurities los ntawm cov khoom siv hluavtaws ntawm cov tshuaj tua kab mob semi-synthetic.Ntawm cov txheej txheem kev npaj impurity feem ntau, flash chromatography yog ib txoj kev siv nyiaj uas muaj txiaj ntsig zoo xws li cov qauv loj thauj khoom, tus nqi qis, txuag lub sijhawm, thiab lwm yam. Flash chromatography tau ua haujlwm ntau dua los ntawm cov kws tshawb fawb hluavtaws.
Nyob rau hauv no ncej, lub ntsiab impurity ntawm ib tug semi-synthetic aminoglycoside tshuaj tua kab mob yog siv raws li cov qauv thiab purified los ntawm ib tug SepaFlash C18AQ cartridge ua ke nrog lub flash chromatography system SepaBean ™ tshuab.Lub hom phiaj cov khoom ua tau raws li qhov yuav tsum tau ua tiav, tawm tswv yim txog kev daws teeb meem zoo rau kev ua kom huv ntawm cov tebchaw no.
Ntu kev sim
Cov qauv no tau ua siab zoo los ntawm lub tuam txhab tshuaj hauv zos.Cov qauv yog ib hom amino polycyclic carbohydrates thiab nws cov qauv molecular zoo ib yam nrog cov tshuaj tua kab mob aminoglycoside.Qhov polarity ntawm cov qauv yog qhov siab, ua rau nws soluble hauv dej.Daim duab schematic ntawm tus qauv tus qauv molecular tau pom nyob rau hauv daim duab 1. Qhov purity ntawm cov qauv nyoos yog kwv yees li 88% raws li kev soj ntsuam los ntawm HPLC.Rau kev ua kom huv ntawm cov tebchaw ntawm cov polarity siab, cov qauv yuav tsum tau khaws cia rau ntawm cov kab C18 li niaj zaus raws li peb cov kev paub dhau los.Yog li ntawd, ib kab C18AQ tau ua haujlwm rau cov qauv purification.
Daim duab 1. Daim duab schematic ntawm tus qauv tus qauv molecular.
Txhawm rau npaj cov qauv kev daws teeb meem, 50 mg crude qauv tau yaj hauv 5 mL dej ntshiab thiab tom qab ntawd ultrasonicated thiaj li ua rau nws dhau los ua cov tshuaj ntshiab.Cov qauv kev daws teeb meem yog tom qab txhaj rau hauv kem flash los ntawm ib qho injector.Kev sim teeb tsa ntawm lub flash purification tau teev nyob rau hauv Table 1.
| Ntsuas | SepaBean™ tshuab 2 | |
| Cartridges | 12 g SepaFlash C18AQ RP flash cartridge (spherical silica, 20 - 45μm, 100 Å, Order naj npawb: SW-5222-012-SP(AQ)) | |
| Lub wavelength | 204 nm, 220 nm | |
| Mobile theem | Solvent A: Dej Cov kuab tshuaj B: Acetonitrile | |
| Tus nqi ntws | 15 ml / min | |
| Sample loading | 50 mg ib | |
| Gradient | Sijhawm (min) | Cov kuab tshuaj B (%) |
| 0 | 0 | |
| 19.0 Nws | 8 | |
| 47.0 Nws | 80 | |
| 52.0 Nws | 80 | |
Cov txiaj ntsig thiab kev sib tham
Lub teeb chromatogram ntawm cov qauv ntawm C18AQ cartridge tau pom nyob rau hauv daim duab 2. Raws li pom hauv daim duab 2, cov qauv zoo heev tau khaws cia rau ntawm C18AQ cartridge.Tom qab lyopolization rau cov khoom sib sau, lub hom phiaj cov khoom muaj purity ntawm 96.2% (raws li qhia hauv daim duab 3) los ntawm HPLC tsom xam.Cov txiaj ntsig tau qhia tias cov khoom siv lim dej tuaj yeem siv ntxiv rau hauv cov kauj ruam tom ntej kev tshawb fawb thiab kev tsim kho.
Daim duab 2. Lub teeb chromatogram ntawm tus qauv ntawm C18AQ cartridge.
Daim duab 3. HPLC chromatogram ntawm lub hom phiaj cov khoom.
Hauv kev xaus, SepaFlash C18AQ RP flash cartridge ua ke nrog lub flash chromatography system SepaBean ™ tshuab tuaj yeem muab cov kev daws teeb meem sai thiab zoo rau kev ua kom huv ntawm cov qauv polar heev.
Hais txog SepaFlash C18AQ RP flash cartridges
Muaj ib tug series ntawm SepaFlash C18AQ RP flash cartridges nrog txawv specifications ntawm Santai Technology (raws li qhia nyob rau hauv Table 2).
| Yam khoom naj npawb | Kem Loj | Tus nqi ntws (ml / min) | Max. Siab (psi/bar) |
| SW-5222-004-SP(AQ) | 5,4g e | 5-15 | 400/27.5 |
| SW-5222-012-SP(AQ) | 20 g ib | 10-25 | 400/27.5 |
| SW-5222-025-SP(AQ) | 33g ua | 10-25 | 400/27.5 |
| SW-5222-040-SP (AQ) | 48g ua | 15-30 | 400/27.5 |
| SW-5222-080-SP(AQ) | 10 5g | 25-50 | 350/24.0 Nws |
| SW-5222-120-SP(AQ) | 15 5g | 30-60 | 300/20.7 |
| SW-5222-220-SP(AQ) | 300 g | 40-80 : kuv | 300/20.7 |
| SW-5222-330-SP(AQ) | 420g ua | 40-80 : kuv | 250/17.2 |
Table 2. SepaFlash C18AQ RP flash cartridges.Cov ntaub ntawv ntim: High-efficiency spherical C18 (AQ)-bonded silica, 20 - 45 μm, 100 Å.
Yog xav paub ntxiv txog cov lus qhia ntxaws ntxaws ntawm SepaBean ™ tshuab, lossis cov ntaub ntawv xaj ntawm SepaFlash series flash cartridges, thov mus saib peb lub vev xaib.
Post lub sij hawm: Oct-26-2018