Объектами исследования служили лекарственные препараты активированного угля, аскорбиновой кислоты, инсулина, ацетилцистеина и подсластителя, в основе которого лежит шестиатомный спирт – сорбитол. Целью работы является разработка методик определения микропримесей тяжелых металлов в готовых фармацевтических препаратах методом атомной абсорбции. В литературном обзоре рассмотрены вопросы влияния микропримесей тяжелых металлов на стабильность лекарственного средства и степень его лечебного воздействия на организм человека. Показано, что контроль содержания тяжелых металлов является важной задачей фармацевтического анализа. Анализ литературных источников позволяет заключить, что атомно-абсорбционная спектрометрия является наиболее распространенным методом, используемым в фармакопейном анализе для определения тяжелых металлов. В ходе экспериментальной части были апробированы методики определения микропримесей тяжелых металлов в субстанциях и готовых лекарственных препаратах, представленных в Государственной Фармакопее Российской Федерации ; внесены корректировки в процедуру анализа с учетом особенностей состава присутствующих добавок в лекарственных препаратах; правильность полученных результатов определения микропримесей тяжелых металлов в образцах активированного угля методом ААС оценена путем сравнения с независимым методом инверсионной вольтамперометрии. / The objects of the study were activated charcoal, ascorbic acid, insulin, acetylcysteine and a sweetener, which is based on six-atom alcohol – sorbitol. The aim of the work is to develop methods for the determination of trace amounts of heavy metals in finished pharmaceutical preparations by atomic absorption. In a literature review, the issues of the influence of trace metals of heavy metals on the stability of the drug and the degree of its therapeutic effect on the human body are considered. It is shown that control of the content of heavy metals is an important task of pharmaceutical analysis. An analysis of literary sources allows us to conclude that atomic absorption spectrometry is the most common method used in pharmacopoeia analysis to determine heavy metals. During the experimental part, methods were tested for determining microimpurities of heavy metals in substances and finished medicinal products presented in the State Pharmacopoeia of the Russian Federation; adjustments were made to the analysis procedure taking into account the characteristics of the composition of the additives present in the drugs; the correctness of the results of determination of microimpurities of heavy metals in activated carbon samples by the AAS method was evaluated by comparison with the independent method of inversion voltammetry.

In 2001 the Declaration on the TRIPS Agreement and Public Health (‘Doha Declaration’), affirmed the right of member states of the World Trade Organisation (‘WTO’) to interpret and implement the TRIPS Agreement as supportive of the protection of public health and, in particular, access to medicines. While initially well-received, consternation soon arose over the interpretation of a specific paragraph in the Doha Declaration dealing with compulsory licensing. After a further two years of deliberation, the WTO Decision on the Interpretation of Paragraph 6 (‘Paragraph-6 Decision’) was announced in August 2003 specifying when countries can import drugs produced elsewhere under compulsory licence. With one third of the world's population is still denied access to essential medicines - a figure which rises to over 50 per cent in Asia and Africa - the problems facing the public health community are two-fold. The first is the capacity of developing countries (‘DCs’) actually to use the flexibilities afforded under the TRIPS Agreement, the Doha Declaration, and the Paragraph- 6 Decision amid stark inequalities in health resources and the world trading system as a whole. These include provisions for compulsory licensing, parallel importation, and addressing imbalances in research and development (‘R&D’). The pending ratification of the Paragraph-6 Decision, from an interim solution to a permanent amendment, is accompanied by considerable uncertainty: will the protections be accessible under the system currently proposed? The second problem concerns the undermining of the above hard-won flexibilities by provisions adopted under various bilateral and regional trade agreements. Known as ‘TRIPS-plus’- or ‘WTO-plus’- measures, the level of intellectual property rights (‘IPRs’) rights protection being negotiated and even adopted under other trade agreements are more restrictive as regards public health protection. These two sources of concern have led to an increase in rather than a lessening of tensions between the public health and trade policy communities. The thesis opens with a brief analysis of the interplay between patents and medicines. This includes an overview of the human rights framework and the right of access to medicines as a manifestation of human rights. The historical development of the TRIPS Agreement, its legitimacy, and the effect of the introduction of patents for pharmaceuticals are critically analysed. The terms of the Doha Declaration as it relates to public health, the Paragraph-6 Decision and its system, the December 2005 Amendment, and the progress made to date on the public health protections available under the TRIPS Agreement are reviewed and discussed in detail. The thesis describes how, despite these important clarifications, concerns as to the capacity of DCs to implement specific measures persist. This thesis further addresses the development of compulsory licensing in India and South Africa, and the legal framework for compulsory licensing in these countries. The role of competition law and constraints faced by DCs in implementing the flexibilities offered by the TRIPS Agreement and Doha Declaration are considered before turning to the threat posed by TRIPS-plus measures and calls for their critical reassessment. The thesis considers the role of the Intergovernmental Working Group on Public Health, Innovation and Intellectual Property (IGWG), the WHO Commission on IPRs, Innovation and Public Health (CIPIH), Patent Pools, and international and multilateral donors in access to medicines. The thesis concludes by reviewing potential ways forward to ensure that access to medicines by the poor living in DCs is secured in all trade agreements. / Mercantile Law / LL.D.

In 2001 the Declaration on the TRIPS Agreement and Public Health (‘Doha Declaration’), affirmed the right of member states of the World Trade Organisation (‘WTO’) to interpret and implement the TRIPS Agreement as supportive of the protection of public health and, in particular, access to medicines. While initially well-received, consternation soon arose over the interpretation of a specific paragraph in the Doha Declaration dealing with compulsory licensing. After a further two years of deliberation, the WTO Decision on the Interpretation of Paragraph 6 (‘Paragraph-6 Decision’) was announced in August 2003 specifying when countries can import drugs produced elsewhere under compulsory licence. With one third of the world's population is still denied access to essential medicines - a figure which rises to over 50 per cent in Asia and Africa - the problems facing the public health community are two-fold. The first is the capacity of developing countries (‘DCs’) actually to use the flexibilities afforded under the TRIPS Agreement, the Doha Declaration, and the Paragraph- 6 Decision amid stark inequalities in health resources and the world trading system as a whole. These include provisions for compulsory licensing, parallel importation, and addressing imbalances in research and development (‘R&D’). The pending ratification of the Paragraph-6 Decision, from an interim solution to a permanent amendment, is accompanied by considerable uncertainty: will the protections be accessible under the system currently proposed? The second problem concerns the undermining of the above hard-won flexibilities by provisions adopted under various bilateral and regional trade agreements. Known as ‘TRIPS-plus’- or ‘WTO-plus’- measures, the level of intellectual property rights (‘IPRs’) rights protection being negotiated and even adopted under other trade agreements are more restrictive as regards public health protection. These two sources of concern have led to an increase in rather than a lessening of tensions between the public health and trade policy communities. The thesis opens with a brief analysis of the interplay between patents and medicines. This includes an overview of the human rights framework and the right of access to medicines as a manifestation of human rights. The historical development of the TRIPS Agreement, its legitimacy, and the effect of the introduction of patents for pharmaceuticals are critically analysed. The terms of the Doha Declaration as it relates to public health, the Paragraph-6 Decision and its system, the December 2005 Amendment, and the progress made to date on the public health protections available under the TRIPS Agreement are reviewed and discussed in detail. The thesis describes how, despite these important clarifications, concerns as to the capacity of DCs to implement specific measures persist. This thesis further addresses the development of compulsory licensing in India and South Africa, and the legal framework for compulsory licensing in these countries. The role of competition law and constraints faced by DCs in implementing the flexibilities offered by the TRIPS Agreement and Doha Declaration are considered before turning to the threat posed by TRIPS-plus measures and calls for their critical reassessment. The thesis considers the role of the Intergovernmental Working Group on Public Health, Innovation and Intellectual Property (IGWG), the WHO Commission on IPRs, Innovation and Public Health (CIPIH), Patent Pools, and international and multilateral donors in access to medicines. The thesis concludes by reviewing potential ways forward to ensure that access to medicines by the poor living in DCs is secured in all trade agreements. / Mercantile Law / LL.D.

Despite the adoption of the Doha Declaration on the TRIPS Agreement and Public Health in 2001, which unequivocally affirmed WTO members’ rights to use compulsory licences and other TRIPS flexibilities to access medicines, thirteen years on, developing countries and least developed countries are still grappling with access to medicines issues and a high disease burden. Despite some well researched and eloquent arguments to the contrary, it is a trite fact that patents remain an impediment to access to medicines by encouraging monopoly prices. The WTO TRIPS Agreement gives members room to legislate in a manner that is sympathetic to access to affordable medicines by providing for exceptions to patentability and the use of patents without the authorisation of the patent holder (TRIPS flexibilities). This study focuses on access to medicines under the TRIPS Agreement from a SADC comparative perspective by interrogating the extent of the domestication of TRIPS provisions promoting access to medicines in the SADC region with specific reference to Botswana, South Africa and Zimbabwe. After establishing that all SADC members, including Seychelles which is yet to be a WTO member have intellectual property (IP) laws in their statute books, this study confirms that while most of the IP provisions may be used to override patents, they are currently not being used by SADC members due to non-IP reasons such as lack of knowledge and political will. The study also engages in comparative discussions of topical occurrences in the context of access to medicines litigation in India, Thailand and Kenya and extracts useful thematic lessons for the SADC region. The study’s overall approach is to extract useful lessons for regional access to medicines from the good experiences of SADC members and other developing country jurisdictions in the context of a south-south bias. The study draws conclusions and recommendations which if implemented will in all likelihood lead to improved access to medicines for SADC citizens, while at the same time respecting the sanctity of patent rights. The study recommends the adoption of a rights-based approach, which will ultimately elevate patient rights over patent rights and urges the region to consider using its LDCs status to issue compulsory licences in the context of TRIPS Article 31 bis while exploring the possibility of local pharmaceutical manufacturing to produce generics, inspired by the experiences of Zimbabwe and current goings on in Mozambique and the use of pooled procurement for the region. The study embraces the rewards theory of patents which should be used to spur innovation and research into diseases of the poor in the SADC region. Civil society activity in the region is also identified as a potential vehicle to drive the move towards access to affordable medicines for all in the SADC region. / Mercantile Law / LL.D.

The earlier optimism generated by the efficacy of antiretroviral drugs in human immuno-deficiency virus (HIV) patients has been dissipated in the face of the enormous chal-lenge of maintaining a nearly perfect adherence indefinitely. This study set to determine the influence of HIV adherence self-efficacy and beliefs about medicines on antiretrovi-ral therapy adherence, with the aim of developing a framework for enhancing antiretrovi-ral therapy (ART) adherence through focused intervention on modifiable factors from study variables that are strongly associated with ART adherence. A descriptive correlational design was used to assess the predictive relationships of HIV adherence Self-Efficacy, Beliefs about Medicines and ART adherence among 232 HIV-infected patients in a large public health facility in Pretoria. Participants' medication be-liefs were assessed using the Beliefs about Medicines Questionnaire, HIV adherence self-efficacy was assessed with HIV adherence self-efficacy scale (HIV-ASES) and ART adherence was assessed using the AIDS Clinical Trial Group questionnaire. Pearson correlation analysis was used to assess bivariate associations among the variables, and multiple regression analysis was used to examine the relationships among the inde-pendent variables and ART adherence. Mean adherence for the 232 participants was 95% (SD=13.2). Correlation analysis re-vealed positive bivariate associations between perceived general harm and overuse of medications, and ART adherence (p<0.05); between specific necessity and concerns about ARVs, and perceived general harm and overuse of medications (p<0.05); be-tween HIV adherence self efficacy and ART non-adherence (p<0.05). Multiple regres-sion analysis showed significance for perceived general harm and overuse of medica-tions on ART adherence (F(1;231)=11,583;p<0,001) with perceived general harmful ef-fects and overuse of medications explaining 4.8% of the variance. There was signifi-cance for HIV adherence self-efficacy on ART non-adherence (F(1;41)=4.440; p<0.041), with HIV-ASES explaining 9,8% of the variance. Based on the results, a framework for enhancing ART adherence was developed. Activities in the framework consist of baseline screening for adherence facilitators and barriers using the beliefs about medicine questionnaire and HIV ASES, this is followed by focused interventions on identified barriers of ART adherence / Health Studies / D.Litt. et Phil. (Health Studies)

The purpose of this study was to explore and describe experiences of HIV/AIDS positive patients using Sesotho traditional medicines at Scott Hospital in Morija, Lesotho. The specific objectives were to explore and describe the experiences and views of patients using Sesotho traditional medicines. The study uded an explorative qualitative design with a sample of seventeen (17) HIV positive adults aged 18-49 years who were purposively sampled. The major findings of the study were that; Sesotho traditional medicines improved the health status of the participants; and also they were of the view that Sesotho traditional medicines work as they beneficially contributed to HIV/AIDS management. The study concludes that Sesotho traditional medicines are believed and understood to play a role in the symptomatic management of HIV/AIDS even though the actual role they play is yet to be proven scientifically. / Department of Health Studies / M.A. (Public Health)

Cette thèse a pour objet l'obligation de sécurité en matière la responsabilité contractuelle à la lumière du droit français et du droit libyen. La recherche tend à répondre aux questions suivantes : Qu'entend-on par sécurité des produits médicaux ? Sur quel fondement juridique peut-on justifier cette obligation ? Quelles sont les difficultés d'application de cette obligation pour traiter les problèmes de produits de santé ? C'est quoi le produits de santé ? Et Le droit de la responsabilité civile libyen est-il parfaitement adapté à la protection de la victime des produits de santé comme dans le droit de la responsabilité français ? Ce questionnement a conduit l'auteur à développer une analyse approfondie de l'obligation de sécurité en manière de la responsabilité contractuelle et le droit de la santé français et libyen. Dans la première partie de la thèse, on constate que la notion d'obligation de sécurité, y compris en matière de la responsabilité contractuelle, a connu une évolution majeure par rapport à l'époque précédant. En fait, l'apparition de la notion d'obligation de sécurité est ancienne puisqu'elle a été créée en France le 21 novembre 1911 à l'occasion du contrat de transport. Elle peut être définie comme « l'obligation de veiller à la sécurité d'une personne ou d'un bien, qui peut être une obligation de résultat ou de moyen ». Certains codes du monde proche-oriental ont adopté la résolution que la Cour de cassation française a prise en 1911 dans le domaine du transport de personnes, comme l'Egypte et le Liban. En 1956, la Cour d'Appel à Alexandrie a conformé l'obligation de sécurité dans le domaine du transport de personnes / This thesis focuses on the safety obligation regarding contractual liability in the light of French law and Libyan law. Research tends to answer the following questions: What is safety of medical products? On what legal basis can we justify that obligation? What are the difficulties in applying this requirement to address issues of health products? What is the health products? The law and civil liability Libya is it perfectly suited to the protection of the victim of health products as in the French liability law? This questioning has led the author to develop a thorough analysis of the safety obligation by way of contractual liability and health law French and Libyan. In the first part of the thesis, we see that the notion of bond security, including with respect to contractual liability, has experienced a major change from the time before. In fact, the emergence of the concept of safety obligation is old since it was founded in France 21 November 1911 at the contract of carriage. It can be defined as "the obligation to ensure the safety of any person or property which may be an obligation of result or means." Some codes of Near Eastern world have adopted the resolution that the French Supreme Court has taken in 1911 in the transportation of persons, such as Egypt and Lebanon. In 1956, the Appeal Court in Alexandria has complied with the requirement of safety in the transportation of persons. Similarly, in Lebanon in the Code of Obligations and Contracts provides in Article 688 that the contract of carriage of persons is the responsibility of the carrier's obligation to lead the traveler, unharmed, to the destination

Esta Dissertação apresenta informações gerais sobre os medicamentos fitoterápicos e os aspectos toxicológicos de uma amostra de dez plantas medicinais comercializadas como medicamentos fitoterápicos no Brasil, pesquisados junto aos principais bancos de dados e fontes públicas de informação. A análise dos medicamentos fitoterápicos cobre as dimensões histórica, econômica e farmacêutica. No tocante aos aspectos toxicológicos, foram avaliados os dados de toxicidade pré-clínica de dez plantas selecionadas, e realizado um levantamento das informações publicadas para Hypericum perforatum e Piper methysticum, relacionadas ao termo toxicidade, segundo três importantes bancos de dados. Adicionalmente, este trabalho aborda as propostas para realização de ensaios de toxicidade pré-clínica para os fitoterápicos segundo a OMS e legislação brasileira, e as normas para avaliação de substâncias químicas segundo a OECD. / This thesis presents general information on herbal medicines and on the toxicological aspects of a sample of ten medicinal plants traded as herbal medicines in Brazil. The survey was carried out in the main databases and public sources of information. The analysis on the herbal medicines encompasses the historical, economic and pharmaceutical dimensions. In what concerns toxicological aspects, data on pre-clinical toxicity were evaluated for Hypericum perforatum and Piper methysticum, these keywords being related to toxicity in three important databases. In addition, this study discusses the proposals for pre-clinical toxicity trials on herbal medicines according to WHO and the Brazilian legislation, and the standards for evaluation of chemical substances according to OECD.

Em 1947, Messmore, obteve uma patente para a retirada do asfalto de petróleo usando fluidos supercríticos. Depois surgiram muitas patentes, principalmente, sobre a descafeinação do café, a extração do lúpulo e da nicotina. Novo estímulo surgiu com o programa da EPA de redução do uso de produtos químicos até 1995, devido às emissões industriais tóxicas. Estas seriam responsáveis pelo aquecimento global do planeta. Muitos trabalhos publicados até hoje, recomendam o uso do CO2 e o método da extração supercrítica, para a obtenção de extratos naturais. Na área farmacêutica, a validação de processos e metodologia analítica está plenamente aceita como atividade necessária e que tem produzido excelentes resultados na melhoria do desempenho industrial e da qualidade dos produtos. Este trabalho validou o método da extração supercrítica usando as sementes do guaranazeiro, planta que cresce naturalmente na Amazônia. O guaraná, possuidor de cafeína é conhecido como estimulante e regenerador do organismo e entre os índios como afrodisíaco. / Abstract not available.

Les médicaments traditionnels à base de plantes (tradimédicaments) sont très utilisés par les populations africaines. Mais leur qualité est difficile à maîtriser, car ce sont des mélanges complexes de plusieurs drogues végétales ou des préparations à base de drogues végétales d’origine souvent inconnue et/ou très variable. Le profil chromatographique des métabolites phytochimiques constitue un outil important pour l’évaluation de la qualité de ces produits.L'objectif de ce travail est de proposer un protocole de préparation des échantillons et d’établissement de profil par chromatographie liquide et chromatographie en phase gazeuse des métabolites apolaires, pour l’évaluation de la qualité des médicaments traditionnels à base de plantes.La méthodologie est basée sur le traitement chimiométrique des profils chromatographiques des métabolites apolaires issus de différents lots de feuilles de Combretum micranthum et Mitracarpus scaber.Le profilage métabolique s’est effectué par chromatographie liquide sur Carbone Graphite Poreux en milieu non-aqueux et par chromatographie en phase gazeuse à haute température, couplées à la spectrométrie de masse, après extraction au dichlorométhane et élimination de la chlorophylle adsorbée sur charbon actif.L'analyse chimiométrique des données utilisant l’analyse PLS-discriminante avec ou sans correction orthogonale du signal, appliquée aux profils chromatographiques des feuilles de Combretum micranthum et Mitracarpus scaber, a montré de faibles différences entre les lots de chaque drogue végétale, et une différenciation claire des deux drogues végétales.Les deux méthodes d'analyse par chromatographie liquide et chromatographie en phase gazeuse permettent de détecter la plupart des métabolites secondaires apolaires bioactifs ou non déjà identifiés dans les feuilles des deux espèces. / The traditional herbal medicines are widely used by African people. But their quality control is difficult, because they are complex mixtures of several herbal drugs or herbal drugs preparations. Their origin is often unknown and/or highly variable. The chromatographic profile of phytochemical metabolites is an important tool for quality assessment of these products.The objective of this work is to propose a protocol for sample preparation and liquid chromatographic and gas chromatographic profiling of non-polar metabolites for quality assessment of africain traditional herbal medicinal products.The methodology is based on the chemometric treatment of chromatographic profiles of non-polar metabolites from different batches of leaves of Combretum micranthum and Mitracarpus scaber.Metabolic profiling is carried out by non-aqueous liquid chromatography on Porous Graphitic Carbon and by high temperature gas chromatography, coupled with mass spectrometry, after extraction with dichloromethane and removal of chlorophyll adsorbed on activated charcoal.The chemometric data analysis using PLS-discriminant analysis with or without orthogonal signal correction applied to the chromatographic profiles of leaves of Combretum micranthum and Mitracarpus scaber showed small differences between batches of each herbal drug, and a clear differentiation two herbal drugs.Both analyses by liquid chromatography and gas chromatography methods detect most non-polar metabolites bioactive or/not already identified in the leaves of both species.