Browsing by Subject "drugs"

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    Open Access
    Intellectual property rights and competition policy: patent rights, access to life-saving drugs in developing and least-developed countries under the TRIPS Agreement and the future of TRIPS after the Article 31 bis Amendment
    (2009) Brucker, Johanna; Davis, Dennis
    This paper examines the interface between intellectual property rights, the issuing of patent protection under the TRIPS Agreement and access to essential medicines. at affordable prices in developing and least-developed countries. It considers the link between patent protection under TRIPS and competition policies by highlighting the clash between intellectual property rights and competition law. The negative impact of intellectual property rights and patent protection on access to available and affordable drugs plays a major role in the discussion related to the international pharmaceutical market. In 1995 the World Trade Organization introduced the Agreement on Trade related Aspects of Intellectual Property Rights. Since the Doha Declaration was adopted in 2001, only a few countries have made use of the flexibilities under TRIPS. This study examines the use of TRIPS flexibilities for the access on essential drugs in developing and least-developed countries and sets out the impact of the Doha Declaration of 2001 and the Amendment to TRIPS of 2005 on the TRIPS Agreement. Governments worldwide are considering whether to ratify the Article 31 bis Amendment. This study argues that a failure to accept and use Article 31 bis will undermine the Doha Decision and the General Council Decision of 2003; it will result in an immense negative impact on health treatment for people in poor small countries. Furthermore, the paper discusses the interface between competition law and the intellectual property system under the TRIPS Agreement after the European Microsoft case and explores the relationship between patent protection under TRIPS, monopolies and anti-competitive behaviour in the market by abusing the dominant position granted by the exclusive patent right. Finally, it highlights factors influencing the future of TRIPS, suggests some action for an effective use of the flexibilities of TRIPS for a broader access on affordable and available medicines in developing and least-developed countries and seeks to examine the reconciliation of the clash between intellectual property rights and competition policies.
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    Open Access
    Polymorphism and cyclodextrin inclusion complexes of antihypertensive agents
    (2006) Mhlongo, Welcome Thabani; Caira, Mino; Nassimbeni, Luigi
    The objective of the project described in this thesis was to isolate polymorphs, solvates and cyclodextrin inclusion complexes of antihypertensive agents. The physical properties of different polymorphs of a given drug are of significant interest to the pharmaceutical industry. The solubility enhancement of poorly soluble drugs by encapsulating them within cyclodextrins is also an important pharmaceutical consideration. The drugs investigated were atenolol, metoprolol, oxprenolol free bases and two salts, namely oxprenolol hydrochloride and metoprolol tartrate. No polymorphs of these antihypertensive agents were isolated but metoprolol yielded a solvate with n-hexane. Single crystals of atenolol, metoprolol, metoprolol tartrate and oxprenolol were isolated and their X-ray structures are reported here for the first time. Inclusion complexes of atenolol, metoprolol and oxprenolol free bases with cyclodextrins were successfully investigated in the solid state. The cyclodextrin hosts used for drug inclusion were P-cyclodextrin, y-cyclodextrin, heptakis(2,6-di-O-methyl)-P-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-P-cyclodextrin and exakis(2,3,6-tri-O-methyl)-acyclodextrin. A new crystal form of heptakis(2,3,6-tri-0-methyl)-P-cyclodextrin as a trihydrate was isolated in an attempt to produce an inclusion complex between this host compound and the drug substance atenolol. The first crystal form of this host compound, a monohydrate, was previously discovered by the Supramolecular Chemistry Research Unit at the University of Cape Town. The various analytical techniques utilised for the characterisation of the solid-state properties of the species were elemental analysis as well as thermal, X-ray diffraction and spectroscopic techniques. Single crystal X-ray diffraction was the principal technique used for investigation of structural features. The structure of metoprolol revealed one molecule per asymmetric unit while the structure of the metoprolol solvate revealed eight molecules of metoprolol and one of n-hexane per asymmetric unit. Structure solution was successful for six cyclodextrin inclusion complexes. The oxprenolol guest molecule was successfully modelled in P-cyclodextrin and heptakis(2,3,6-tri-0-methyl)-P-cyclodextrin. Metoprolol was successfully modelled in hexakis(2,3,6-tri-O-methyl)-a-cyclodextrin but could not be modelled in heptakis(2,3,6- tri-O-methyl)-p-cyclodextrin and P-cyclodextrin due to its severe disorder. The computed powder X-ray diffraction (PXRD) patterns of the oxprenolol-˜- cyclodextrin (OXPRBCD) and atenolol-P-cyclodextrin (ATBCD) inclusion complexes were different from their experimental PXRD patterns. This indicated that phase transformation had occurred upon grinding the single crystals for each of these complexes. These two complexes crystallise in space group Pl [with unit cell parameters a˜ 18, b ˜15 and c ˜ 15 A]; thus, they are isostructural. However, their experimental PXRD patterns are different from each other. The comparison of these experimental PXRDs with published reference patterns for P-cyclodextrin complexes showed that grinding OXPRBCD transformed this material into a form crystallising in the space group P21 while grinding ATBCD resulted in its transformation to a phase belonging to the space group C2. Such transformations have not been reported previously. Among the free bases studied, atenolol is the only one that is currently commercially available as a medicinal agent. Exploitation of metoprolol and oxprenolol free bases as guests for cyclodextrin inclusion has led to the isolation and full characterisation of new inclusion complexes that have potential for further pharmaceutical development.
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    Open Access
    Polymorphism and cyclodextrin inclusion complexes of antihypertensive agents
    (2006) Mhlongo, Welcome Thabani; Caira, Mino; Nassimbeni, Luigi
    The objective of the project described in this thesis was to isolate polymorphs, solvates and cyclodextrin inclusion complexes of antihypertensive agents. The physical properties of different polymorphs of a given drug are of significant interest to the pharmaceutical industry. The solubility enhancement of poorly soluble drugs by encapsulating them within cyclodextrins is also an important pharmaceutical consideration. The drugs investigated were atenolol, metoprolol, oxprenolol free bases and two salts, namely oxprenolol hydrochloride and metoprolol tartrate. No polymorphs of these antihypertensive agents were isolated but metoprolol yielded a solvate with n-hexane. Single crystals of atenolol, metoprolol, metoprolol tartrate and oxprenolol were isolated and their X-ray structures are reported here for the first time. Inclusion complexes of atenolol, metoprolol and oxprenolol free bases with cyclodextrins were successfully investigated in the solid state. The cyclodextrin hosts used for drug inclusion were P-cyclodextrin, y-cyclodextrin, heptakis(2,6-di-O-methyl)-P-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-P-cyclodextrin and exakis(2,3,6-tri-O-methyl)-acyclodextrin. A new crystal form of heptakis(2,3,6-tri-0-methyl)-P-cyclodextrin as a trihydrate was isolated in an attempt to produce an inclusion complex between this host compound and the drug substance atenolol. The first crystal form of this host compound, a monohydrate, was previously discovered by the Supramolecular Chemistry Research Unit at the University of Cape Town. The various analytical techniques utilised for the characterisation of the solid-state properties of the species were elemental analysis as well as thermal, X-ray diffraction and spectroscopic techniques. Single crystal X-ray diffraction was the principal technique used for investigation of structural features. The structure of metoprolol revealed one molecule per asymmetric unit while the structure of the metoprolol solvate revealed eight molecules of metoprolol and one of n-hexane per asymmetric unit. Structure solution was successful for six cyclodextrin inclusion complexes. The oxprenolol guest molecule was successfully modelled in P-cyclodextrin and heptakis(2,3,6-tri-0-methyl)-P-cyclodextrin. Metoprolol was successfully modelled in hexakis(2,3,6-tri-O-methyl)-a-cyclodextrin but could not be modelled in heptakis(2,3,6- tri-O-methyl)-p-cyclodextrin and P-cyclodextrin due to its severe disorder. The computed powder X-ray diffraction (PXRD) patterns of the oxprenolol-˜- cyclodextrin (OXPRBCD) and atenolol-P-cyclodextrin (ATBCD) inclusion complexes were different from their experimental PXRD patterns. This indicated that phase transformation had occurred upon grinding the single crystals for each of these complexes. These two complexes crystallise in space group Pl [with unit cell parameters a˜ 18, b ˜15 and c ˜ 15 A]; thus, they are isostructural. However, their experimental PXRD patterns are different from each other. The comparison of these experimental PXRDs with published reference patterns for P-cyclodextrin complexes showed that grinding OXPRBCD transformed this material into a form crystallising in the space group P21 while grinding ATBCD resulted in its transformation to a phase belonging to the space group C2. Such transformations have not been reported previously. Among the free bases studied, atenolol is the only one that is currently commercially available as a medicinal agent. Exploitation of metoprolol and oxprenolol free bases as guests for cyclodextrin inclusion has led to the isolation and full characterisation of new inclusion complexes that have potential for further pharmaceutical development.
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    Open Access
    Reducing substance use and sexual risk behaviour among men who have sex with men in South Africa
    (2016) Parry, Charles DH
    Abstract Men who have sex with men have been identified as a population at risk of acquiring and transmitting HIV. Studies in South Africa have reported a high prevalence of HIV, as well as high levels of alcohol and other drug use, among men who have sex with men, and the use of substances (alcohol and drugs) to facilitate their sexual encounters. Since 2007, interventions focused on prevention have been rolled out to vulnerable men who have sex with men and who also use alcohol or other drugs. The interventions include community-based outreach; provision of information on HIV/AIDS, substance abuse, and safer sex practices; and the development of risk-reduction plans. Among 195 men who participated in our study, there were significant reductions in the proportion who used cannabis and ecstasy, including the use of these drugs during sex. No reduction was observed in the use of any other substances. In general, after the intervention our participants reported less frequent use of alcohol and drugs and greater engagement in safer sexual practices. Despite these encouraging findings, the combination of substance use while engaging in sex had actually increased. The study findings suggest that interventions that target men who have sex with men, and who use alcohol and other drugs, could reduce risk behaviours in this population.
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    The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy
    (2017) Trauner, Andrej; Liu, Qingyun; Via, Laura E; Liu, Xin; Ruan, Xianglin; Liang, Lili; Shi, Huimin; Chen, Ying; Wang, Ziling; Liang, Ruixia; Zhang, Wei; Wei, Wang; Gao, Jingcai; Sun, Gang; Brites, Daniela; England, Kathleen; Zhang, Guolong; Gagneux, Sébastien; Barry, Clifton E; Gao, Qian
    BACKGROUND: Combination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics. RESULTS: By combining very deep whole genome sequencing (~1000-fold genome-wide coverage) with sequential sputum sampling, we were able to detect transient genetic diversity driven by the apparently continuous turnover of minor alleles, which could serve as the source of drug-resistant bacteria. However, we report that treatment efficacy has a clear impact on the population dynamics: sufficient drug pressure bears a clear signature of purifying selection leading to apparent genetic stability. In contrast, M. tuberculosis populations subject to less drug pressure show markedly different dynamics, including cases of acquisition of additional drug resistance. CONCLUSIONS: Our findings show that for a pathogen like M. tuberculosis, which is well adapted to the human host, purifying selection constrains the evolutionary trajectory to resistance in effectively treated individuals. Nonetheless, we also report a continuous turnover of minor variants, which could give rise to the emergence of drug resistance in cases of drug pressure weakening. Monitoring bacterial population dynamics could therefore provide an informative metric for assessing the efficacy of novel drug combinations.