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Protein macromolecules immobilization onto polymer carriers
Šitnerová, Michaela ; Holas, Ondřej (advisor) ; Ondrejček, Pavel (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Consultant: PharmDr. Ondřej Holas, Ph.D. Student: Michaela Šitnerová Title of Thesis: Protein macromolecules immobilization onto polymer carriers Enzymes are unique biocatalysts because of their properties. They are highly specific, selective and functional even under mild reaction conditions. The method of immobilization is used to increase their operational stability, activity and possible reuse. This process allows the wide use of enzymes in industry, for example in the food industry, analytical chemistry, chemical synthesis and in the pharmaceutical industry. The aim of my thesis was immobilized enzyme acetylcholinesterase (AChE) on the surface pellets of microcrystalline cellulose (MCC). Used method was simple sorption, immobilization using glutaraldehyde, and TEMPO oxidation using MCC. Well known Ellman's method served to measure the activity of AChE. The absorbance of the solution with the immobilized AChE was measured spectrophotometrically at 412 nm.
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A study of the compaction process for the pellets made of microcrystalline cellulose.
Trpělková, Žofie ; Ondrejček, Pavel (advisor) ; Holas, Ondřej (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: Mgr. Pavel Ondrejček, Ph.D. Student: Žofie Trpělková Title: A study of a compaction process of microcrystalline cellulose pellets This work is aimed at the comparison of two types of microcrystalline cellulose (Comprecel 102 a Avicel PH-200) with two types of pellets made of microcrystalline cellulose (Cellets 100 a Cellets 200). Important properties for the compaction into tablets were analyzed in these materials. The particle size distribution, the content of moisture, the bulk and tapped density, the flowability, the angle of repose and the Hausner ratio were evaluated. Furthermore, the compaction process was described by using the force displacement method and the three-exponential equation. Finally, the radial strength and the friability of tablets prepared by using two different compaction forces were evaluated. The results proved that both types of pellets have much better flow properties than powdered microcrystalline celluloses. This is primarily caused by the narrow particle size distribution, higher bulk and tapped density and the significantly smoother surface of pellets. Better flow properties of the pellets also influenced the parameters of the force-displacement...
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Pyrazine derivatives as potential drugs V.
Horová, Anna ; Marek, Jan (advisor) ; Holas, Ondřej (referee)
Charles University in Prague, Pharmaceutical Faculty in Hradec Králové Department: Department of Pharmaceutical Chemistry and Drug Control Diplomate: Anna Horová Supervisor: PharmDr. Jan Marek, Ph.D. Title of Diploma Thesis: Pyrazine derivatives as potential drugs V. TBC is a specific world-wide infectious disease, compounded by increased migrations of people, the spread of HIV and the growth of MDR-TB, including extremely resistant strains. Precisely for the growth of MDR-TB resistant mycobacteria the work is focused on the preparation and development of other possible antituberculosis drugs (Pyrazine derivatives). Research into new medications lays emphasis on altering the effects of enzymes important for the vitality of mycobacteria. As part of my diploma thesis, pyrazine derivative modifications of clinical pyrazinamide medications were prepared. PZA is an important part of the short-term TBC treatment, having a sterile effect and the ability to work in an acidic environment and has a significant synergy with rifampicin. The small PZA molecule is a precursor to the pyrazine acid activated by pyrazinamide or nicotinamide. Hydrolysis of PZA in mycobacterial cells create Pyrazinecarboxylic acid (POA). In the experimental part, we have examined the variation molecules pyrazinamide and preparing the...
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Rheological behavior of branched polyesters
Martiška, Juraj ; Šnejdrová, Eva (advisor) ; Holas, Ondřej (referee)
CHARLES UNIVERSITY IN PRAGUE Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical technology Name: Juraj Martiska Title of diploma thesis: Rheological behavior of branched polyesters Supervisor: PharmDr. Eva Snejdrova, Ph.D. This thesis studies rheological and thermal properties of potencial polyester drug carrier composed of an equimolar proportion of D,L-lactic and glycolic acids, branched with tripentaerythritol at a concentration of 3%, and its analogs plasticized with methyl salicylate at different concentrations. The theoretical part deals with the characterization of polymers, their plasticizing and rotational rheometry. In the experimental part were prepared plasticized polyesters then were determined their glass transition temperatures using a DSC, and on rotational rheometer was tested their rheological behavior. According to the results of thermal analysis, methyl salicylate significantly lowers the glass transition temperature of the tested polyester and seems to be suitable plasticizer. The resulting data of rheological analyzes show that 3T plasticized polymer exhibits pseudoplastic behavior at 25řC and concentration of methyl salicylate 20% when the viscosity is highest. Viscosity of polymer systems significantly decreases with increasing temperature and concentration...
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The influence of the dwell time on the parameters of the stress relaxation test for lactose and calcium hydrogen phosphate.
Straková, Markéta ; Svačinová, Petra (advisor) ; Holas, Ondřej (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical technology Consultant: Mgr. Petra Svačinová, Ph.D. Student: Straková Markéta Title of Thesis: The influence of dwell time on the parameters of the stress relaxation test for lactose and calcium hydrogen phosphate The aim of this thesis is to find out viscoelastic properties of pharmaceutical excipients and to evaluate the tensile strength of tablets made of them. The theoretical part describes used materials, these are lactose, calcium hydrogen phosphate and magnesium stearate. The thesis also deals with the stress relaxation test, its evaluation and usage. Tensile strength, calculation and various factors that affect tensile strength are described in the text. The experimental part deals with viscoelastic properties of used materials and their mixtures with lubricant using the stress relaxation test. Different dwell times (60 s, 120 s, 180 s, 240 s, 300 s, 360 s, 420 s, 480 s, 540 s, 600 s) were used for individual measurements. The relation between elasticity parameters (A1, A2, A3) and plasticity parameters (P1, P2, P3) depending on the dwell time was investigated. As for calcium hydrogen phosphate, the dwell time 180 - 240 seconds was found as the most appropriate. As for lactose, the optimum dwell...
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Synthesis and biological evaluation of tacrine-amantadine derivatives
Král, Jan ; Opletalová, Veronika (advisor) ; Holas, Ondřej (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Jan Král Supervisor: doc. RNDr. Veronika Opletalová, Ph.D. Consultant: PharmDr. Jan Korábečný, Ph.D. Title of diploma thesis: Synthesis and biological evaluation of tacrine-amantadine derivatives Alzheimer's disease (AD) is a fatal neurodegenerative disorder of brain. Nowadays there is only paliative treatment available, which can be further subdivided into two groups: acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonist. Donepezil, rivastigmine and galantamine represents AChEIs currently available for AD treatment. Tacrine is the first AChEIs to be approved for AD treatment, however, it was withdrawn from the market due to its side effects, especially due to its hepatotoxicity. 7-Methoxytacrine (7-MEOTA) is less toxic tacrine derivative preserving pharmacological profile of tacrine. This diploma thesis describes synthesis of multifunctional 7-MEOTA- amantadine derivatives as potential drugs to confront AD. Using Ellmanʼs method, we have established their efficacy to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro. All new synthesized hybrids from 7-MEOTA- amantadine family proved to be better...
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Polymeric stabilizers maintaining the supersaturation solubility of itraconazole nanocrystals after dissolution process
Kubačková, Jana ; Holas, Ondřej (advisor) ; Paraskevopoulos, Georgios (referee)
Title of thesis: Polymeric stabilizers maintaining the saturation solubility of itraconazole nanocrystals after dissolution process Author: Jana Kubačková Department: Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, Ph.D. Specialized supervisor: Assoc. Prof. Leena Peltonen, Ph.D. The increase of bioavailability of poorly water soluble drugs is still an issue. One of the techniques improving aqueous drug substance solubility, and consequently enhancing bioavailability, is formation of nanoparticles. However, the bioavailability is determined by the concentration of the dissolved drug achieved at the time of absorption. This fact emphasizes the importance of the maintenance of the high solubility until the absorption area is reached. Sufficiently stabilised nanocrystalline drugs offer a solution to this problem. In this thesis, the solid nanoparticle formations of an antifungal agent itraconazole (ITZ) are presented. Wet milling was employed to create the nanosuspension stabilised by binary mixture of stabilisers or by a single stabiliser. An aggregation inhibitor Poloxamer 407 (F127) in the combination with a polymeric precipitation inhibitor hydroxypropyl methylcellulose (HPMC) or polyvinyl pyrrolidone (PVP) at different ratios, or a single precipitation inhibitor, were utilised. The...
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Molecular modeling study of potential mycobacterial enoyl-reductase inhibitors
Slovák, František ; Holas, Ondřej (advisor) ; Zitko, Jan (referee)
Charles University in Prague, Pharmaceutical Faculty in Hradec Králové Department: Department of Pharmaceutical Chemistry and Drug Control Diplomate: František Slovák Supervisor: PharmDr. Ondřej Holas, Ph.D. Title of Diploma Thesis: Molecular modeling study of potential mycobacterial enoyl ACP reductase inhibitors. Tuberculosis is a worldwide spread infectious disease. The biggest problem of our time are completely and multi resistant strains of Mycobacterium tuberculosis that do not respond to currently known drugs. The main reason for high resistance and drug resistance is a bacillus composition of its cell wall. It contains a high proportion of mycolic acids. The synthesis of mycolic acids takes several steps. The final step is a catalytic reduction by enzyme enoyl - ACP reductase ( InhA ). This work was focused on finding new potential substances that would be able to inhibit this enzyme. There were used methods of computing and molecular modeling to search these substances. Adjusting of crystallographic structures ran in the program Maestro and docking in the MOE program. Over the 30 000 thousand molecules from the ZND (Zinc Natural Derivates) were tested by molecular docking on 3 crystallographic structures of InhA enzyme. 8 of these molecules were selected from this amount because their...
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The impact of an injection drug administration on an oxidative stress development in laboratory Guinea pig model
Kračmarová, Alžběta ; Mokrý, Milan (advisor) ; Holas, Ondřej (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Msc. Alžběta Kračmarová Consultant assoc. prof. Miroslav Pohanka, RNDr, PhD. Title of Thesis The impact of an injection drug administration on an oxidative stress development in laboratory Guinea pig model Injections of drugs are considered to be standard procedures used in experimental work with laboratory animals. Laboratory rodents are sensitive to a way of handling. For this reason stress caused by the injection leads to alteration of various physiological processes. Rise of body temperature, tachycardia, elevated or declined blood glucose level or oxidative imbalance may influence results in disparate experiments. Aim of our experiment was to clarify an impact of intramuscular injection on development of an oxidative imbalance. The laboratory Guinea pigs were sacrificed one hour after the intramuscular injection of saline solution. After that, blood and selected organs were collected. Ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS), carbonylated proteins, superoxide dismutase activity and glutathione reductase activity as markers of oxidative state and caspase 3 activity as marker of apoptosis were measured in the tissue homogenates....
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Colorimetric assay based on immobilized acetylcholinesterase for the determination of efficiency of inhibitors used in pharmacotherapy
Drobík, Oto ; Opletalová, Veronika (advisor) ; Holas, Ondřej (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate Mgr. Oto Drobík Consultant Assoc. Prof. Veronika Opletalová, Ph.D. Title of Thesis Colorimetric assay based on immobilized acetylcholinesterase for the determination of efficiency of inhibitors used in pharmacotherapy. There is a large number of substances belonging to acetylcholinesterase (AChE) inhibitors that are used in agriculture, for example as insecticides or pesticides. They are also used as nerve paralytic agents for military purposes. Some of them have been applied in treatment of diseases such as myasthenia gravis or Alzheimer's disease. Within the thesis, AChE was successfully immobilized on the bottom of a 96 well microplate, using gelatine. By means of a colorimetric method, the reaction conditions were optimized; the resistance of the immobilized AChE against the washout was also tested. Furthermore, an inhibition rate of AChE by solvents was determined and kinetic parameters of an enzymatic reaction were evaluated. Tacrine and pyridostigmine were tested as representatives of AChE inhibitors. A long-term stability test of the immobilized AChE was further performed. The results that have been achieved indicate that the method described is...
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