Simulacija proizvodnje intermedijera za proizvodnju lijekova u različitim reaktorskim sustavima

undergraduate thesis

• Title (english): Simulation of pharmaceutical precursor production in different reactor types
• Author: Katarina Komljenović
• Mentor: Ana Vrsalović Presečki (mentor)
• Committee member: Ana Vrsalović Presečki (predsjednik povjerenstva)
• Committee member: Vesna Tomašić (član povjerenstva)
• Committee member: Jasna Prlić Kardum (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2017-09-20, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering; Reaction Engineering

Abstract

Statini predstavljaju skupinu lijekova sa sposobnošću snižavanja kolesterola LDL (engl. Low Density Lipoprotein; LDL) i lipoproteina male gustoće inhibiranjem HMG-CoA (3-hidroksi-3-metilglutaril-koenzimA) reduktaza. Inhibicija navedenog enzima je vrlo važna u sprečavanju bolesti poput hiperkolesterolemije, koronarne bolesti, srčanih te kardiovaskularnih bolesti. U radu je provedena simulacija sinteze 6-kloro-3,5-dihidroksi heksanala, (laktola) koji je bitan prekursor u dobivanju statina. Sinteza je provedena u reakciji dvostruke aldolne adicije acetaldehida i kloroacetaldehida katalizirane enzimom 2-deoksiriboza-5-fosfat aldolazom (DERA). Određena je kinetika svih reakcija koje se odvijaju tijekom sinteze laktola katalizirane enzimom DERA te su kinetike opisane Michaelis-Menteničinim izrazima. Postavljen je matematički model sinteze laktola u kotlastom reaktoru, kotlastom reaktoru s dotokom i protočno kotlastom reaktoru. U model je također uključena deaktivacija enzima uzrokovana prisutnosti aldehida koje imaju negativan utjecaj na stabilnost enzima, te je opisana kinetikom drugog reda. Na temelju dobivenih rezultata simulacije, uspoređeni su različiti početni uvjeti sinteze laktola u različitim tipovima reaktora.

Abstract (english)

Statins represents a group of medicines with the ability to lower cholesterol LDL and low density lipoproteins by inhibition HMG-CoA reductase (3-hydroxy-3-methylglutaryl-coenzyme A), which is very important in the prevention of diseases such as hypercholesterolemia, coronary diseases, cardiac and cardiovascular diseases. In this study the simulation of the synthesis of an important precursor of statin, (3R, 5R)-6-chloro-3,5-dihydroxyhexanal (lactone) was carried out. The synthesis was performed in the reaction of double aldol addition of acetaldehyde and chloroacetaldehyde catalyzed by the enzyme 2-deoxyribose-5-phosphate aldolase (DERA-e). The kinetics of all reactions that occurs during lactol synthesis catalyzed by DERA has been determined and kinetics was described by Michaelis-Menten equations. A mathematical model of lactol synthesis in batch reactor, fed-batch reactor and continuous tank flow reactor was established. The model also included the enzyme deactivation caused by the presence of various aldehydes that have a negative impact on the enzyme stability and was described by the second order kinetics. Based on the results of the simulation, the different initial conditions of lactol synthesis in different reactor mode were compared.

• Keywords: 2-deoksiriboza-5-fosfat aldolaza; statin; deaktivacija enzima; kinetika enzima; matematičko modeliranje
• Keywords (english): 2-deoxyribose-5-phosphate aldolase; statin; enzyme deactivation; enzyme kinetics; mathematical modelling
• Language: croatian
• URN:NBN: urn:nbn:hr:149:278053
• Project: Number: 635595; Title: Sustainable industrial processes based on a C-C bond-forming enzyme platform; Acronym: CARBAZYMES; Leader: Zvjezdana Findrik Blažević; Jurisdiction: eu; Funder: EC; Funding stream: H2020
• Study programme: Title: Chemical Engineering - Undergraduate study; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/ prvostupnica (baccalaureus/baccalaurea) inženjer/inženjerka kemijskog inženjerstva (sveučilišni/a prvostupnik/ prvostupnica (baccalaureus/baccalaurea) inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Closed access
• Created on: 2021-03-15 11:52:10