Mingzu Yang, Bo Xu
Isicelo se-R&D Center
Isingeniso
Ama-antibiotics yikilasi lama-metabolites esibili akhiqizwa amagciwane (okuhlanganisa amagciwane, isikhunta, i-actinomycetes) noma izinhlanganisela ezifanayo ezihlanganiswa ngamakhemikhali noma ezihlanganiswe kancane.Ama-antibiotic angavimbela ukukhula nokuphila kwamanye ama-microorganisms.Isibulala-magciwane sokuqala esatholwa umuntu, i-penicillin, satholwa isazi sezinto eziphilayo saseBrithani u-Alexander Fleming ngo-1928. Wabona ukuthi amagciwane aseduze nesikhunta awakwazi ukukhula esitsheni se-staphylococcus esasingcoliswe isikhunta.Waveza ukuthi isikhunta kumelwe sikhiphe into elwa namagciwane, ayiqamba ngokuthi i-penicillin ngo-1928. Nokho, izithako ezisebenzayo azizange zihlanzwe ngaleso sikhathi.Ngo-1939, u-Ernst Chain noHoward Florey base-Oxford University banquma ukwenza umuthi owawungase welaphe izifo ezibangelwa amagciwane.Ngemva kokuxhumana noFleming ukuze bathole amagciwane, bakhiphe futhi bahlanza i-penicillin ezinhlobonhlobo.Ukuze bathuthuke ngempumelelo i-penicillin njengesidakamizwa sokwelapha, uFleming, uChain noFlorey babelane ngomklomelo kaNobel Kwezokwelapha ngo-1945.
Ama-antibiotic asetshenziswa njengama-antibacterial agents ukwelapha noma ukuvimbela izifo ezibangelwa amagciwane.Kunezigaba eziningana eziyinhloko zama-antibiotic asetshenziswa njengama-antibacterial agents: ama-β-lactam antibiotics (okuhlanganisa i-penicillin, i-cephalosporin, njll.), ama-antibiotic e-aminoglycoside, ama-macrolide antibiotics, ama-tetracycline antibiotics, i-chloramphenicol (ingqikithi yama-synthetic antibiotic), njll. Imithombo yama-antibiotic ihlanganisa ukuvutshelwa kwezinto eziphilayo, i-semi-synthesis kanye nokuhlanganiswa okuphelele.Imithi elwa namagciwane ekhiqizwa ukuvutshelwa kwebhayoloji idinga ukushintshwa ngokwesakhiwo ngezindlela zamakhemikhali ngenxa yokuzinza kwamakhemikhali, imiphumela emibi enobuthi, i-antibacterial spectrum nezinye izinkinga.Ngemuva kokuguqulwa kwamakhemikhali, ama-antibiotics angakwazi ukuzuza ukuqina okukhulayo, ukunciphisa imiphumela emibi enobuthi, ukwanda kwe-antibacterial spectrum, ukunciphisa ukumelana nezidakamizwa, ukutholakala kwe-bioavailability okuthuthukisiwe, kanjalo nomphumela othuthukisiwe wokwelashwa kwezidakamizwa.Ngakho-ke, ama-antibiotic e-semi-synthetic okwamanje ayisiqondiso esithandwa kakhulu ekwakhiweni kwemithi elwa namagciwane.
Ekuthuthukisweni kwama-semi-synthetic antibiotics, ama-antibiotic anezakhiwo zokuhlanzeka okuphansi, inqwaba yemikhiqizo kanye nezingxenye eziyinkimbinkimbi njengoba etholakala emikhiqizweni yokuvutshelwa kwe-microbial.Kulokhu, ukuhlaziya nokulawulwa kokungcola ku-semi-synthetic antibiotics kubaluleke kakhulu.Ukuze uhlonze ngempumelelo futhi ubonise ukungcola, kuyadingeka ukuthola inani elanele lokungcola emkhiqizweni wokwenziwa we-semi-synthetic antibiotics.Phakathi kwezindlela ezivame ukusetshenziswa zokulungiselela ukungcola, i-flash chromatography iyindlela engabizi kakhulu enezinzuzo ezifana nesamba esikhulu sesampula sokulayisha, izindleko eziphansi, ukonga isikhathi, njll. I-Flash chromatography iye yasetshenziswa kakhulu abacwaningi bokwenziwa.
Kulokhu okuthunyelwe, ukungcola okuyinhloko kwesibulala-magciwane se-semi-synthetic aminoglycoside kwasetshenziswa njengesampula futhi kwahlanzwa ngekhatriji ye-SepaFlash C18AQ ehlanganiswe nohlelo lwe-flash chromatography umshini we-SepaBean™.Umkhiqizo ohlosiwe ohlangabezana nezidingo watholwa ngempumelelo, ophakamisa isisombululo esisebenza kahle kakhulu sokuhlanzwa kwalezi zinhlanganisela.
Isigaba Sokuhlola
Isampula linikezwe ngomusa inkampani yendawo eyenza imithi.Isampula bekuwuhlobo lwama-amino polycyclic carbohydrates futhi ukwakheka kwawo kwamangqamuzana kwakufana nama-aminoglycoside antibiotics.I-polarity yesampula yayiphezulu kakhulu, iyenza inyibilike kakhulu emanzini.Umdwebo oyisikimu wesakhiwo samangqamuzana esampula uboniswe kuMfanekiso 1. Ukuhlanzeka kwesampula eluhlaza kwakucishe kube ngu-88% njengoba kuhlaziywe yi-HPLC.Ukuze kuhlanzwe lezi zinhlanganisela ze-polarity ephezulu, isampula ngeke ligcinwe kumakholomu avamile e-C18 ngokuya ngesipiliyoni sethu sangaphambilini.Ngakho-ke, ikholomu ye-C18AQ yasetshenziswa ukuze kuhlanzwe isampula.
Umfanekiso 1. Umdwebo wohlelo lwesakhiwo semolekyuli yesampula.
Ukulungiselela isisombululo sesampula, isampula ye-50 mg eluhlaza yachithwa emanzini ahlanzekile angu-5 ml bese i-ultrasonicated ukuze kube yisixazululo esicacile ngokuphelele.Isixazululo sesampula sabe sesijovwa kukholamu yefuleshi ngomjovo.Ukusethwa kokuhlolwa kokuhlanzwa kwe-flash kufakwe kuhlu kuThebula 1.
| Insimbi | Umshini we-SepaBean™ 2 | |
| Amakhatriji | 12 g SepaFlash C18AQ RP flash cartridge (silica eyindilinga, 20 - 45μm, 100 Å, inombolo ye-oda:SW-5222-012-SP(AQ)) | |
| Ubude begagasi | 204 nm, 220 nm | |
| Isigaba seselula | I-solvent A: Amanzi I-solvent B: I-Acetonitrile | |
| Izinga lokugeleza | 15 mL/min | |
| Isampula iyalayisha | 50 mg | |
| I-Gradient | Isikhathi (imizuzu) | I-solvent B (%) |
| 0 | 0 | |
| 19.0 | 8 | |
| 47.0 | 80 | |
| 52.0 | 80 | |
Imiphumela nengxoxo
I-flash chromatogram yesampula ku-cartridge ye-C18AQ iboniswe kuMfanekiso 2. Njengoba kuboniswe kuMfanekiso 2, isampula ye-polar ephezulu igcinwe ngokuphumelelayo ku-cartridge ye-C18AQ.Ngemuva kwe-lyopholization yezingxenye eziqoqiwe, umkhiqizo ohlosiwe ube nobumsulwa be-96.2% (njengoba kuboniswe kumfanekiso wesi-3) ngokuhlaziywa kwe-HPLC.Imiphumela ibonise ukuthi umkhiqizo ohlanziwe ungasetshenziswa futhi esinyathelweni esilandelayo socwaningo nokuthuthukiswa.
Umfanekiso 2. I-flash chromatogram yesampula ku-cartridge ye-C18AQ.
Umfanekiso 3. Ichromatogram ye-HPLC yomkhiqizo oqondiwe.
Sengiphetha, i-SepaFlash C18AQ RP flash cartridge ehlanganiswe nohlelo lwe-flash chromatography umshini we-SepaBean™ unganikeza isisombululo esisheshayo nesisebenzayo sokuhlanzwa kwamasampuli asezindaweni ezishisayo.
Mayelana ne-SepaFlash C18AQ RP flash cartridges
Kukhona uchungechunge lwama-flash cartridges e-SepaFlash C18AQ RP anemininingwane ehlukene evela ku-Santa Technology (njengoba kukhonjisiwe kuThebula 2).
| Inombolo Yento | Usayizi Wekholomu | Isilinganiso sokugeleza (mL/min) | Ubukhulu.Ingcindezi (i-psi/ibha) |
| I-SW-5222-004-SP(AQ) | 5.4 g | 5-15 | 400/27.5 |
| I-SW-5222-012-SP(AQ) | 20 g | 10-25 | 400/27.5 |
| I-SW-5222-025-SP(AQ) | awu 33g | 10-25 | 400/27.5 |
| I-SW-5222-040-SP(AQ) | awu 48g | 15-30 | 400/27.5 |
| I-SW-5222-080-SP(AQ) | 105 g | 25-50 | 350/24.0 |
| I-SW-5222-120-SP(AQ) | awu 155g | 30-60 | 300/20.7 |
| I-SW-5222-220-SP(AQ) | 300 g | 40-80 | 300/20.7 |
| I-SW-5222-330-SP(AQ) | awu 420g | 40-80 | 250/17.2 |
Ithebula 2. I-SepaFlash C18AQ RP flash cartridges.Izinto zokupakisha: I-silica eyisiyingi esebenza kahle kakhulu i-C18(AQ)-eboshiwe, 20 - 45 μm, 100 Å.
Ukuze uthole ulwazi olwengeziwe mayelana nemininingwane eningiliziwe yomshini we-SepaBean™, noma imininingwane yoku-oda kuma-flash cartridge ochungechunge lwe-SepaFlash, sicela uvakashele iwebhusayithi yethu.
Isikhathi sokuthumela: Oct-26-2018