Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Júlia Jurčáková Supervisor: RNDr. Jakub Hofman PhD. Title of diploma thesis: The assessment of inhibitory effects of selected targeted anticancer drugs on the activity of ABC drug eflux trasporters. Lung cancer is the leading cause of death within oncological diseases. Non-small cell lung carcinoma (NSCLC) accounts for about 85% of all lung cancer, and its major subtypes include adenocarcinoma and squamous cell carcinoma. In addition to surgery, radiotherapy and chemotherapy, the use of targeted low-molecular substances, which target tumor cells with higher specificity, has recently been used in treatment. The two main causes of death in cancer patients are the formation of metastases and the development of multidrug resistance (MDR). This may also be caused by overexpression of the efflux transporters. ATP-binding cassette (ABC) transporters are groups of transmembrane pumps that use energy in the form of ATP to transfer a wide range of substrates. In particular, P-glycoprotein (ABCB1), breast cancer-resistance protein (ABCG2) and multidrug resistance-associated protein 1 (ABCC1) are associated with MDR. Inhibition of these transporters increases the amount of cytostatic substrate within the...

This diploma thesis observes representation and evolution of medical advertisement, products and services in print. This evolution is shown on comparing the two eras, the "first republic" and modern Czech Republic. The studied years of 1928 and 2008 demarcate the period of 80 years of transformation of advertisement market, but some of the rules are the same. The goal of this diploma thesis is to describe contemporary advertisement in chosen printed media, the magazines for public without specialization or further attributes "Světozor" and "Týden" serve for the research. The thesis observes which services and products were offered, in context of what and which methods were used. The text goes on from introduction to the topic and issues and analysis of particular samples from magazines to their comparation. The results of diploma thesis is the evaluation of used rules, according to the media themselves and the timeline. Thesis deals with the regulation of medical advertisement aswell. To compare them and increase the number of samples, the advertising of cosmetics sold in pharmacies is added. .

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Jan Juhász Supervisor: Prof. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Treatment of lower extremity peripheral artery disease The lower extremities ischemia is a disease caused most often by atherosclerosis during which the lumen in lower limb arteries becomes narrow. Its prevalence is increasing, especially in the developed countries. The disease can be asymptomatic and symptomatic. The symptoms are very unpleasant and decrease patient's quality of life. Advanced stages of the disease may be life threatening. Therefore, it is vital to timely and correctly diagnose the illness. During the therapy, it is possible to use pharmacological as well as non-pharmacological procedures, and, preferably, a combination of the two types of treatment. The pharmacotherapy can be divided into several parts. The prevention of atherosclerotic complications makes use of preventive measures and antiplatelet therapy to reduce the cardiovascular risk. The symptoms therapy focuses on improving patients' quality of life by prescribing the vasoactive medications cilostazol, naftidrofuryl or pentoxifylin. The critical limb ischemia therapy uses prostaglandin analogues alprostadil, iloprost, limaprost or...

Highly-exact structural characterization is the crucial step in the development and manufacturing process of pharmaceutical materials. Their structural composition is, however, often very complex and hardly identifiable. The eligible way for obtaining definite structural interpretation of these systems appears the high-resolution solid-state nuclear magnetic resonance (ssNMR) spectroscopy. For this purpose the reliable tool - the ssNMR toolbox for comprehensive characterization of various pharmaceutical solids is described. The rigorous optimization of ssNMR techniques is carried out on enormous number of measured samples containing active pharmaceutical ingredients (APIs) with systems ranging from APIs formulated in solid dispersions to pure forms revealing extensive molecular disorder. In this study the influence of polymeric matrix on the creation of solid dispersion type susceptible for finely tuned controlled drug release is likewise discussed. The distinction between variable structural alignments of API molecules in 3D dimension of complicated pharmaceutical solids is allowed via simple strategy - factor analysis applied to hardly describable ssNMR spectra (13 C CP/MAS NMR and 19 F MAS NMR). The results of this ssNMR investigation contribute to better understanding of solid dispersion...

Goals: Prepare a case study on the transition to the new OTC medicines groups with restrictions. To evaluate the positives and negatives, which brought the introduction of the group - with OTC restrictions. Pick up generally applicable principles and specify non-functional parts of the system. Method: For data processing method was applied theoretical research. Literature was searched in the database of the Czech National Library - Klementinum, WHO database, TRIBUNE and interfaces of News portals. The instrumental case study was processed for a detailed insight into the issues. The case study is also based on the analysis of the legal framework of the Czech Republic. The documents provided by SÚKL are used for financial analysis. As another method the stakeholder analysis was used - analysis of opinions of people involved in the drug policy. Results: The case study shows that switching medicines containing PSE to the limited group of OTC to prevent producers of drugs buing drugs in Czech pharmacies, but it did not reduce the amount of drugs produced in the country. Producers started to import precursors from abroad. The whole new system established in 2009 was correct in principle, but failed in practice. State Institute for Drug Control or other stakeholders in drug policy have not been able to resolve the ensuing complications.

The thesis deals with a current issue of the relationship between pharmaceutical manufacturers and physicians. Its objective it to find out the influence pharmaceutical companies exercise on a physician decision making on providing health care, what influences physicians´ medication selection and whether there are differences in individual physicians´ specializations. Based on the findings of the research the thesis aims at creating suggestions of changes in legislation concerning the relationship between a physician and a pharmaceutical company and the establishment of new rules. The introductory theoretical part describes the role of a physician and pharmaceutical companies in the current health care system. In the practical part the method of qualitative research, characteristics of the research database and results of standardized interviews using direct quotations are presented. Discussion is focused on comparing the research results with the views of media articles and the own opinion of the thesis writer. In the conclusive part of the thesis existing rules are described and the writer recommends some measures which may lead to changes in public attitudes. Another issue, which goes beyond this thesis and could become a topic for further research, is also outlined. Based on the collected data, in the closing part of the work a hypothesis for a potential quantitative research is stated. The contribution of the thesis is based on the possibility of clarifying complicated relations between physicians and pharmaceutical manufacturers both for professional and general public.

1 ABSTRACT SPECIFIC OF PATENT LAW IN PHARMACEUTICAL INDUSTRY This thesis scopes on particularities of patent law with regard to pharmaceuticals. It describes the basics of patent law while focusing mainly on international treaties, in particular on systems established by EPC and TRIPS. The patent system in USA and in the Czech Republic is also noted. This thesis is divided into seven chapters. In the first chapter named sources of law international institutions, treaties and situation in European union, USA and Czech Republic are described here. This chapter also deals with basic legal instruments such as patent, corporate invention or utility model. The next chapter is focused on individual conditions that need to be met in order to grant a certain patent - the most basic are novelty, inventive step and industrial applicability. The following chapter deals with problems associated with costly development of new drugs and the need of companies to get the longest possible protection for their inventions. A special chapter addresses exceptions to the stiff patent regulation. Described in the next chapter is the compulsory license, a legal instrument not very particular in the Czech Republic but relevant in some developing countries used in order to secure better availability of drugs to society. Other...

The purpose of this thesis is valuation of the Zentiva, k.s. enterprise. The value of this enterprise will be determined as of 1.1. 2014, using the discounted free cash flows valuation method. This thesis is divided into a theoretical and a practical section. The theoretical section acquaints readers with the key terms and methods used during valuation. The theoretical section includes a chapter about the pharmaceutical industry and will familiarise readers with current factors influencing this sector, such as price regulation in the field of medicaments, demographic development, life style and others, which have significant impact on determining the company's final value. The practical section consists of a description of Zentiva, k.s., a strategic analysis, financial analysis, execution of a financial plan and, finally, actual valuation. The result of this thesis is valuation of the enterprise, taking into account socio- economic factors to determine its final value.

This dissertation is focused on the controlled release of drugs from a biodegradable amphiphilic hydrogel based on hydrophobic poly(lactic acid), poly(glycolic acid) and hydrophilic poly(ethylene glycol) (PLGA-PEG-PLGA, ABA) and its modification with itaconic anhydride (ITA). The resulting ,-itaconyl(PLGA-PEG-PLGA) copolymer is referred to as ITA/PLGA-PEG-PLGA/ITA or ITA/ABA/ITA. Itaconic acid provides reactive double bonds and a functional carboxyl group at the ends of the PLGA-PEG-PLGA copolymer chain, thereby rendering the modified ITA/ABA/ITA copolymer less hydrophobic and offering the possibility of forming a carrier for hydrophilic drug substances. These functional copolymers are thermosensitive and change in the external environment (e.g. temperature) causes a sol-gel phase transition due to the formation of micellar structure. The bioactive substances can thus be mixed with a copolymer which is in a low viscous phase (sol phase) and subsequently the mixture can be injected into patient's body at the target site where it forms a gel at 37 °C. This hydrogel becomes a drug depot, which gradually releases the active substance. Prediction of the substance’s release profile from the hydrogel is an effective tool to determine the frequency of administration, potentially enhancing efficacy, and assessment of side effects associated with dosing. The analgesic paracetamol and the sulfonamide antibiotic sulfathiazole were used as model drugs, representing hydrophilic and hydrophobic substances, respectively. The active substances had a significant effect on the resulting hydrogel stiffness. Type of solvent, incubation medium and nanohydroxyapatite also influenced on the gel stiffness and subsequent stability of the hydrogel-drug system. Controlled release of drugs took place in simulated conditions of the human body. Verification of Korsmeyer-Peppas (KP) drug-release model is also discussed in this thesis. The KP model was found suitable for simulating the release of sulfathiazole from ABA and ITA/ABA/ITA hydrogels. On the contrary, the performance of KP model was not suitable for describing the release of paracetamol from the ABA hydrogels. Therefore, a new regression model suitable for both buffered simulated media and water has been proposed. The proposed model fitted better the release of both sulfathiazole and paracetamol from composite material prepared from ABA hydrogel and nanohydroxyapatite.

This diploma thesis deals with the efficiency of removal of pharmaceuticals from drinking water by selected adsorption materials. The first part describes sources of pharmaceuticals in drinking water and possible ways of contaminating water by pharmaceuticals. Subsequently, the pharmaceuticals most commonly found in the environment - nonsteroidal anti-inflammatory drugs, antibiotics, psychiatric drugs and sex hormones - are described in more detail. Next, the thesis describes the processes used for removal of pharmaceuticals. These are activated carbon adsorption, membrane processes and advanced oxidation processes. The last chapter of the theoretical part of the thesis deals with water treatment plants, where the technologies for removing drugs are already in operation. In the practical part of this thesis an experiment was performed and evaluated, for a purpose of comparing the efficiency of selected sorption materials in the removal of diclofenac from water. Filtrasorb F100, Bayoxide E33 and GEH were used.