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od Teucrium polium kaj INS-1E kletki xxii ^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION PP - 150 Jelena Gavrilovic, Jelena Kukic, Zvezdana Doslov -Kokorus, Zoran Maksimovic Antioxidant potential of Achillea millefolium from Vrsacki breg………………….… ……….…..308 PP - 151 Nada Spajic, Jelena Kukic, Silvana Petrovic, Marjan Niketic, Mira Stojanovic Antioxidant potential of Achillea fraasii and A. ageratifolia ssp. serbica (Asteraceae) ………....309 PP - 152 Simic M., Vucicevic D., Milenkovic M., Miajlovic N., Savic M., Kovacevic N Antimicrobial and bacterial antiadhesive activity of Vaccinium vitis -idaea…....................…...…310 PP - 153 Nabila Benhammou, Fawzia Atik Bekkara, Tatjana Kadifkova Panovska Evaluation of the antifungal and antioxidant activities of essential oils of Pistacia lentiscus and Pistacia atlantica…...……... ...................... ....................................... …....….311 PP - 154 Vesna Kuntic, Ivana Filipovic Anticoagulant effects of rutin and hesperidin chelates…...…… …………………………. ...….….312 PP - 155 Stevic T., Bigovic D., Samardzic Z., Radanovic D. Antimicrobial activity of Arnica montana L.…...……... ........................................................ .….….313 PP - 156 Tamara Bosnic, Dzenita Softic, Maida Brackovic, Samra Suvalija, Sasa Pilipovic The regulatory status of medicinal and aromatic plants and their products in Federation Bosnia and Herzegovina (FB&H)…...……...….… ………………………………... .314 PP - 157 Tamara Bosnic, Dzenita Softic, Diana Jerg -Simanovic, Sasa Pilipovic Quality control of the herbal drug Equiseti herba (Horsetail) from the market…...… ….…...….315 PP - 158 Vesna Ceran, Jovan Popovic, Jelena Cvejic, Milica Atanackovic Soybean extract as antioxidant active and dietary supplement ingredient….............……...….….316 PP - 159 Rusica Kolakovic, Bosko Bondzulic, Jelena Kukic, Silvana Petrovic, Milka Jadranin, Miroslav Novakovic, Dejan Gocevac Investigation on antioxidant activity of extracts of Alchemilla velebitica Borbas. (Rosaceae )…...……...….… …………………………………….. .317 PP - 160 Dusica Arsic, Bojka Blagojevic, Snezana Kostadinovic Our experience with medical plant s in fito-therapy of stress…...…….................................. ….….318 PP - 161 Bojka Blagojevic, Mara Vlajkovic, Dusica Arsic, Milena Stankovic Contents of heavy metals in medical plants – Hazard to people health…...…… ……….....….….319 PP - 162 Arsic I., Djordjevic S., Runjaic -Antic D., Psodorov Dj., Tadic V. Our experience in preparation and characterization herbs additivs as dietary food supplements…...……...….… ……………………………………... .320 PP - 163 Desa Jakimova, Tatjana Kadifkova Panovska Quantitative d etermination Afaltoxin B1 in peanuts…...……...… ……………………….….321-322 Desa Jakimova, Tatjana Kadifkova -Panovska Opredeluvawe na Alfatoksinot B1 vo kikiriki PP - 164 S. Sobajic., I. Miletic., B. Gjorgjevic., I. Stankovic. Significance of proficiency tests in quality control of food laboratories – our experiences .…….323 PP - 165 Sober M., Djedjibegovic J., Marjanovic A., Skrbo A., Djono S. Spectrophotometric determination of sulfites in dietary products…...…… ………….........….….324 PP - 166 Slavica Razic, An tonije Onjia Pattern Recognition Techniques Applied to Classification of Wines Based on Elemental Analysis by Atomic Spectroscopy …...……………………...….….325 PP - 167 M. Curcic Jovanovic, D. Djukic -Cosic, M. Ilic, M. Mitrovic, S. Torbica, A. Djukic V. Matovic. Fluoride content in spring waters of mountains in Serbia…...……... ................................... …..….326 PP - 168 Rade Injac, Branislava Srdjenovic, Matevz Prijatelj, Marija Boskovic, Nevena Grujic, Borut Strukelj, Biljana Govedarica, Natasa Radic, Zika Lepojevic. Comparative analysis of caffeine, theobromine and theophyline in food and drinks by MEKC and HPLC.....……...………………………………………….. ..….327 xxiii ^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION PP - 169 T. Petreska, K. Mladenovska, L. Acevska, M. J. Pavlova, M. Petrovska, L. Petrusevska -Tozi Viability of Lactobacillus casei in fermented soymilk after drying and storage……………. 328-329 T. Petreska, K. Mladenovska, L. Acevska, M. J. M. Petrovska, L . Petru{evska -Tozi Vitalnost na Lactobacillus casei vo fermentirano soja mleko vo uslovi na su{ewe i ~uvawe PP - 170 Biljana Bauer Petrovska; Mitko Karadelev; Olga Kirovska Cigulevska Selen content of some edible mushrooms from Republic of Macedonia………… .………….330-331 Biljana Bauer Petrovska; Mitko Karadelev; Olga Kirovska Cigulevska Sodr`ina na selen vo nekoi jadlivi gabi od Republika Makedonija PP - 171 Biljana Bauer Petrovska, Mitko Karadelev, Svetlana Kulevanova Biological value of proteins of some edible spe cies of mushrooms from Republic of Macedonia ………………………………………………………………..….332 -333 Biljana Bauer Petrovska, Mitko Karadelev, Svetlana Kulevanova Biolo{ka vrednost na proteinite na nekoi jadlivi vidovi gabi od Republika Makedonija PP - 172 Olga Kirovska Cigulevska; Biljana Bauer Petrovska; Mitko Karadelev Accumulation of toxic metals in various mushroom species from different regions of the Republic of Macedonia …………………………………….….334 -335 Olga Kirovska Cigulevska, Biljana Bauer Petrovska, Mit ko Karadelev Akumulirawe na toksi~ni metali vo razni vidovi gabi od pove}e regioni vo Republika Makedonija PP - 173 Emanuela Kostadinova, Kalina Alipieva, Marina Stefova, Trajce Stafilov, Daniela Antonova1, Ljuba Evstatieva, Vlado Matevski, Svetlana Kul evanova, Gjoshe Stefkov, Vassya Bankova Chemical composition of the essential oils of three Micromeria species growing in Macedonia and Bulgaria…………………………………………………….….…. .336-337 Emanuela Kostadinova, Kalina Alipieva, Marina Stefova, Traj~e Stafilov, Daniela Antonova, Quba Evstatieva, Vlado Matevski, Svetlana Kulevanova, \o{e Stefkov, Vasja Bankova Hemiski sostav na eteri~nite masla od tri vida Micromeria koi rastat vo Makedonija i Bugarija PP - 174 Skrbo A, Sober M, Marjanovic A, Djedjibegovic J . Pharmacy from XIII to XVI century……………………………………………...…… …….…….338 PP - 175 Skrbo A., Sober M., Marjanovic A., Djedjibegovic J. „ATTARI“ and „LJEKARUSE“ – their contribution to development of pharmacy………………………………………………………….…….……….3 39 INDEKS NA AVTORI / AUTHOR INDEX ........................................................................... 341 xxiv PLENARNI KONGRESNI PREDAVAWA – CPL CONGRESS PLENARY LECTURES – CPL CPL 1-4 Targeted Nanoparticles for Cancer Therapy Atilla Hincal, Erem Bilensoy Hacettepe University Faculty of Pharmacy Department of Pharmaceutical Technology 06100 Ankara Turkey e-mail: ahincal@hacettepe.edu.tr Cancer is still the leading cause of death among all maladies and the rate of death from cancer has not changed between 1950s to 2000s. This indicates that cancer chemotherapy suffers from a range of limitations. Cancer chemo- therapy is currently associated with various major drawbacks including the toxicity and severe side effects arising from parameters like formulation factors (solubilizers e.g. Cremophor EL or Polysorbate 80 used for paclitaxel and doc- etaxel respectively), pharmacokinetic variability of anticancer agents as a result of their poor aqueous solubility and impaired hydrolytic or photo-stability and non-selective cytotoxicity of these chemotherapeutic drugs which affect healthy cells as well as tumor cells. Multidrug drug resistance is also another important challenge in cancer chemo- therapy which limits the use of anticancer agents. Lack of oral and self-applied chemotherapy which is beneficial for improving patient compliance is a limiting factor for the effectiveness of cancer chemotherapy as a consequence of the significantly low oral bioavailability of anticancer agents. Nanoparticles are submicron colloidal carriers with matrix or membrane type structure respectively for nanospheres and nanocapsules generally made out of polymers or polysaccharides of different nature among which synthetic polymers like Polylactide-co-glycolide, Polylactic acid, Poly-epsilon-caprolactone, Polyalkylcyanoacryla- tes and natural polymers such as albumin, chitosan, gelatin and oligosaccharides like dextran or amphiphilic cyclo- dextrins are the most frequently used macromolecules. Nanoparticles were first designed to fit the “Magic Bullet” con- cept first introduced by Ehrlich and are reported to possess the advantage of accumulation in tumor tissues as a result of the leaky and abnormal vasculature of the cancer site due to the small particle size of these carrier systems which are mostly less than 400nm. As well as the enhanced permeation through tumor vasculature, a molecule entering the tumor site is not regularly drained as a consequence of the lack of a functioning lymphatic drainage system. This is the so-called EPR (Enhanced Permeation and Retention) effect and the major passive targeting pathway for nanopar- ticles. Different nanoparticles in the form of nanospheres or nanocapsules have been studied using various polymers and macromolecules which are capable of encapsulating a wide range of cancer chemotherapeutics. Passive target- ing, however, is limited to RES uptake after injection of nanoparticles which takes placed by the portin binding of nanoparticles called opsonization and taking up of these particles by macrophages to RES organs. This phenomenon limits the effective delivery of anticancer drug-loaded nanoparticles to cancer cells located in RES”organs such as liver and spleen. As an alternative to passive targeting through the EPR effect, several active targeting strategies have been applied to nanoparticles including size reduction to less than 100 nm and surface modification with hydrophilic poly- mers such as PEG or PEO or specific antigens to repel possible proteins to avoid opsonization This is believed to allow the prolonged circulation of injected nanoparticles which result in higher accumulation tumor site. A more sophisticated technique for targeting nanoparticles to tumor cells is surface modification of nanopar- ticles with tumor-specific antigens. Some antigens with specific affinity to substrates overexpressed on tumor cell surface such as folate or transferrin can be grafted to the polymer along with PEG residues which spontaneously form the nanoparticle with different techniques such as emulsification/solvent evaporation or nanoprecipitation techniques to improve the active targeting to tumor specifically. pH-sensitive or thermosensitive polymers adjusted to react to slightly acidic tumor pH or hyperthermia can also be used to prepare nanoparticles or to coat pre-formed nanoparti- cles to obtain active targeting during chemotherapy. Magnetic fields may be used to orient the nanoparticles towards the tumor site. Polymeric nanoparticles are also reported to overcome multidrug resistance acquired during chemo- therapy by creatimng microconcentration gradients and bypassing active transport systems into the cell. These car- rier systems are also used for imaging and diagnosis of tumors due to their affinity to cancer cells and different research groups are working on the optimization of nanoparticles targeted to tumor cells for diagnosis and therapy. Macedonian pharmaceutical bulletin 53 (1,2) 2 (2007) CPL - 1 2 ^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION European Quality Standards for Medicines: the European Pharmacopoeia and the European Directorate for the Quality of Medicines & HealthCare (EDQM) Peter Castle European Pharmacopoeia Department, European Directorate for the Quality of Medicines & HealthCare, Council of Europe, Strasbourg, France The European Pharmacopoeia is elaborated jointly under an international convention by 36 European coun- tries* and the quality standards (monographs) it contains are mandatory for all medicines marketed in the 36 Member States. Compliance with monographs is required by Directives of the European Union, which is a signatory to the Convention. The standards are also recognised in most of the affiliated observer States**. The monographs cover all types of medicines used in Europe: The central body is the European Pharmacopoeia Commission composed of delegations from the Member States. The Commission is responsible for the work programme and policy decisions but delegates the detailed work on monographs, including laboratory verification, to a series of groups of experts and working parties, with experts from the Member States and observer states. The European Pharmacopoeia is published as a book, a CD-ROM and an on-line internet version, with three annual updates, corresponding to the three sessions of the Commission. Over the past 15 years, EDQM has developed a series of activities centred on the European Pharmacopoeia: Certification of suitability of monographs Harmonisation of standards with the Japanese Pharmacopoeia and the United States Pharmacopoeia Co-ordination of activities of official medicines control laboratories, with emphasis on quality assurance Biological standardisation programme, with emphasis on alternatives to animal testing EDQM has recently taken over responsibility for the Council of Europe activities in the fields of blood trans- fusion and organ transplantation. *Member States: Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Montenegro, Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, the former Yugoslav Republic of Macedonia, Turkey, United Kingdom and the European Union. **Observers: European: Albania, Georgia, Republic of Belarus, Russian Federation and Ukraine; Non-European: Algeria, Australia, Brazil, Canada, China, Israel, Kazakhstan, Madagascar, Malaysia, Morocco, Senegal, Syria, Tunisia, United States of America, World Health Organisation. Macedonian pharmaceutical bulletin 53 (1,2) 3 (2007) CPL - 2 3 ^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION Chemical substances (active substance, excipients, natural and synthetic) Vaccines and sera (human and veterinary) Antibiotics Blood products Biological and biotechnological products Radiopharmaceutical preparations Herbal drugs and herbal drug preparations Dosage form general monographs Fats and fatty oils Glass and plastic containers Medicinal gases Homoeopathic starting materials, stocks and manufacturing methods Recent trends in pharmaceutical analysis F. David, P. Sandra Research Institute for Chromatography, Kortrijk, Belgium and Ghent University, Belgium Current trends in pharmaceutical analysis focus on high productivity and „information rich analyses“. This can by imple- mentation of high throughput and high resolution analytical methods. In response to these needs, innovative technologies and instru- mental developments for separation and detection have been introduced and implementing these developments can have a signifi- cant inpact on pharmaceutical analysis. In this presentation, recent developments in GC snd HPLC methods for pharmaceutical analysis are presented and illus- trated with typical examples. State-of-art GC equipment using new electronic pressure control and capillary flow technology can significant increase sample throughtput for purity and assay determination and also new tools are available to increase productivity in residual solvent analysis. In HPLC, the introduction of sub-two micron packing material and the broader pressure, flow and temperature range of analytical equipment also opens new perspectives for fast HPLC and/or high resolution HPLC, reaching „GC-like“ peak capacities. In additio, special attention will be paid to the analysis of suspected genotoxic impurities in drug substances. For the deter- mination of these impurities at very low levels, state-of-the-art sample prepaation, analysis and detection are needed. Several approach- es will be demonstrated fot this new class of target solutes. Macedonian pharmaceutical bulletin 53 (1,2) 4 (2007) CPL - 3 4 ^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION Toward a novel class of antithrombotic compounds with dual function Danijel Kikelj, Janez Ilash University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia Thromboembolic diseases are a leading cause of mortality and morbidity in the developed world. Therefore, alternatives to existing antithrombotic drugs are a challenging medicinal chemistry goal. During the last 10 years, a major progress in the development of novel antithrombotic agents has been achieved with selective thrombin and factor Xa inhibitors which inhibit blood coagulation as well as with antiaggregatory fibrinogen receptor antago- nists. A combination of various antiaggregatory and anticoagulant agents, e.g. thrombin inhibitor and glycoprotein IIb/IIIa antagonist, is frequently used in clinical practice in order to achieve an efficient antithrombotic effect. Recently, we introduced a concept of composite antithrombotic drugs combining in the same molecule both throm- bin inhibitory and fibrinogen receptor antagonistic activity by merging pharmacophores D-Phe-Pro-Arg and Arg- Gly-Asp into one molecule which will bind with the same moieties to the thrombin active site and to the fibrino- gen receptor. We investigated both peptidic and peptidomimetic versions of target dual antithrombotic compounds with conjugated and highly integrated pharmacophores comprising different mimetics of crucial moieties. The tar- get compounds were prepared in several iterative cycles, involving molecular modelling, chemical synthesis and biological testing. The lecture will present a progress in the design of this type of antithrombotic compounds with dual function over the last few years. Macedonian pharmaceutical bulletin 53 (1,2) 5 (2007) CPL - 4 5 ^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION NH N H 2 NH N H 2 N H N O O OH O N H NH 2 NH N H N H O H O NH 2 O O O N H NH 2 NH O H O N H D-Phe-Pro-Arg Arg-Gly-Asp thrombin inhibitor (anticoagulant) inhibitor of binding of fibrinogen to fibrinogen receptor (antiaggregatory) FPD RGD ''composite antithrombotic drugs'' expected to inhibit thrombin and inhibit aggregation peptidic linker or peptidomimetic scaffold 6 AKADEMSKA SEKCIJA Sekciski predavawa SL 1-3 Kratki soop{tenija SP 1-11 ACADEMIC SECTION Section lectures SL 1-3 Short presentation SP 1-11 Continuous education in Pharmaceutical Sciences – the art of survival Bjarne Fjalland The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark Lifelong learning has become a necessity in a Europe characterised by rapid technological and economic change. Constant need of new knowledge accentuates these challenges – underlining the need for a continuous updating and renewal of knowledge, skills and wider competences. This also applies for the pharmaceutical area. Pharmacists works with topics along all areas of the drug development process from drug discovery to clini- cal pharmacy. It is therefore necessary to develop post graduate courses/programmes covering all areas of the drug development process. In Denmark we have for the moment three professional Master´s programmes running within the pharmaceu- tical area • Master of Industrial Drug Development (MIND) • Master of Drug Management (MDM) • Master of Pharmaceutical Regulatory Affairs (MPRA) These programmes are offered to pharmacists and other academic professionals on part time basis – each cov- ering one year of full time study (60 ECTS credit points). The programmes comprises about 8 compulsory courses (typical 2½-5 ECTS credit points each), some elec- tive courses and a Master´s project. Each course can also be followed individually. Enrolment at the Master´s pro- grammes is not necessary to follow the individual courses. The realisation of lifelong learning at international level is however complicated by the lack of communication and co-operation between education and training providers and authorities at different level. Barriers between institu- tions and countries not only prevent access to education and training but also prevent an efficient use of knowledge and competences already acquired. The lecture will focus on the Danish assess to create Master´s programmes for academic professionals work- ing in the pharmaceutical sector and the content of these programmes. Macedonian pharmaceutical bulletin 53 (1,2) 8 (2007) SL - 1 8 ^ETVRTI KONGRES NA FARMACIJATA NA MAKEDONIJA SO ME\UNARODNO U^ESTVO FOURTH CONGRESS OF PHARMACY OF MACEDONIA WITH INTERNATIONAL PARTICIPATION |
