20.500.12556/DKUM-42649 PORAZDELITEV KLAVULANSKE KISLINE MED VODO IN ORGANSKIM TOPILOM PARTITIONING OF CLAVULANIC ACID IN WATER-ORGANIC SOLVENT SYSTEM Diplomsko delo prikazuje študijo klavulanske kisline (KK) iz obstoječe literature. Ta je pomemben betalaktamski antibiotik in učinkuje proti bakterijam, katere so zmožne razviti odpornost proti tem antibiotikom. Učinkuje na način, da ireverzibilno acilira serinsko OH skupino v aktivnem mestu encima s posnemanjem normalnega substrata. Vendar je v primerjavi s široko spektralnimi antibiotiki njena uporaba omejena. Kot posledica tega se ne uporablja kot samostojno antibakterijsko sredstvo, največkrat služi kot dodatek drugim širokospektralnim antibiotikom, ki ne delujejo ob prisotnosti -laktamaze. Naravno proizvaja klavulansko kislino mikroorganizem Streptomyces clavuligerus z biokemijskim postopkom-fermentacijo. Velik vpliv na proizvodnjo kisline imajo: količina ogljika, dušika, fosfatov, prekuzorji in način delovanja bioreaktorjev. Pridobljeno klavulansko kislino porazdelijo iz filtrirane in nakisane fermentacijske brozge v organsko topilo z ekstrakcijo. Primerna topila so: etilacetat, butil acetat, 2-butanol, n-butanol in metil izobutil keton. Ekstrakcija je bila izvedena z etil acetatom, ki kljub temu, da ima manjši porazdelitveni koeficient (K=0,65) od n-butanola (K=1,85), ima večjo selektivnost za klavulansko kislino kakor za amoksicilin, topnost vode je v njem manjša in ima nižje vrelišče, s čimer je olajšan proces koncentriranja vzorca. Iz organske faze jo nato lahko ločijo z uparevanjem topila, kar povzroča večje stroške in razgradnjo KK. Hirata in sodelavci6 poročajo o postopku priprave čistega in stabilnega kalijevega klavulanata z direktnim obarjanjem klavulanske kisline iz organske faze s kalijevim 2-etil heksanoatom. Pri optimizirani kombinaciji koncentracij (15 mg/mL KK in 0,3 M kalijevega 2-etil heksanoata) so dosegli velik izkoristek (69 %). Thesis shows the study of clavulanic acid (CA) in the existing literature. This is an important beta-lactam antibiotic and is effective against bacteria, which are able to develop resistance to this antibiotic. It works in such a way that irreversible acylated serine OH group in the active site of lactamase by mimicking the normal substrate. However, in comparison with broad-spectrum antibiotics, its application is limited. As a result, it is not been possible to use clavulanic acid as a solely administered antibacterial product and is most often co-formulated with other broad-spectrum antibiotics, which do not work in the presence of -lactamase. Naturally is clavulanic acid produced by organism Streptomyces clavuligerus in biochemical process - fermentation. Significant impact on the production of acid are: the amount of carbon, nitrogen, phosphate, precursors and operation mode of the bioreactor. Obtained clavulanic acid is distributed from the filtered and acidified fermentation broth into an organic solvent by extraction. Suitable solvents are ethyl acetate, butyl acetate, 2-butanol, n-butanol and methyl isobutyl ketone. Extraction was carried out with ethyl acetate, which, although it has a smaller partition coefficient (K = 0.65) from n-butanol (K = 1.85), has a greater selectivity for the clavulanic acid as amoxicillin, the solubility of water in the it is smaller and has a lower boiling point, making it easier for the process of concentrating the sample. Solvent can be separated from organic phase via evaporation, and that can cause higher operating costs and decomposition of CA. Hirata at.el6 report a method for production of pure and stable potassium clavulanate using direct precipitation of clavulanic acid from organic phase using potassium 2-ethyl hexanoate. The optimal concentration (15 mg/mL KK and 0.3 M potassium 2-ethyl hexanoate) gives high yield (69 %). klavulanska kislina biosinteza fermentacija ekstrakcija clavulanic acid biosynthesis fermentation extraction true true false [K. Kogovšek] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2013-10-02 10:45:39 2013-10-03 14:09:21 2022-05-07 03:07:54 2021-04-27 03:20:17 2013 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 663.953.031.4(043.2) 17452822 URN:SI:UM:DK:MOKUH2DH VS_Kogovsek_Kristjan_2013.pdf VS_Kogovsek_Kristjan_2013.pdf 1 82333E701C693DC510EB4C8810BF4DCE aede370cd941a75245b1bb419d114606ca1f68c2c1191328eaf9797e49475088 77876b47-7c0a-11eb-bb7a-00155d0001ca https://dk.um.si/Dokument.php?lang=slv&id=59835 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0