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使用抗精神病药物硫利达嗪作为二线防御药物的有效疗法,以及硫利达嗪为涵盖各种“新用途”的新专利所提供的潜力。

Effective therapy with the neuroleptic thioridazine as an adjunct to second line of defence drugs, and the potential that thioridazine offers for new patents that cover a variety of "new uses".

作者信息

Amaral Leonard, Viveiros Miguel, Molnar Joseph, Kristiansen Jette E

机构信息

Grupo de Micobactérias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Portugal.

出版信息

Recent Pat Antiinfect Drug Discov. 2011 May;6(2):84-7. doi: 10.2174/157489111796064542.

DOI:10.2174/157489111796064542
PMID:21548876
Abstract

New and active infections of tuberculosis continue to increase globally. Although antibiotic susceptible infections can be readily cured with isoniazide and rifampicin, infections resistant to these two antibiotics, named Multi-Drug Resistant TB (MDR TB), are problematic for therapy, extol high costs in terms of human suffering and finances, and when these MDR infections progress to Extensive Drug Resistant TB (XDR TB) status, they are not only difficult to treat, they produce high levels of mortality regardless of therapeutic modality employed. The neuroleptic thioridazine (TZ) has been shown to have wide spectrum in vitro and ex vivo activities against antibiotic susceptible, MDR and XDR strains, and has been successfully used for curing mice of active tuberculosis produced by antibiotic susceptible and MDR strains, and has cured 10 out of 12 XDR TB patients when used in combination with three antibiotics to which the XDR TB patients were non-responsive. Mycobacterium tuberculosis TZ has been recommended for "Compassionate Therapy" of MDR/XDR TB infections whose prognoses are significantly serious and anticipated to result in mortality. This review of TZ activity and its potential to cure MDR/XDR TB supports the contention that this neuroleptic offers patenting opportunities for "New Use". The motivation for patents therefore is expected to rapidly bring TZ to the forefront for therapy of MDR/XDR TB and therefore, the striving for new patents is expected to contribute to the prevention of new infections of antibiotic resistant tuberculosis.

摘要

全球范围内,新发和活动性结核病感染病例持续增加。尽管对抗生素敏感的感染可以通过异烟肼和利福平轻易治愈,但对这两种抗生素耐药的感染,即耐多药结核病(MDR TB),在治疗方面存在问题,在人类痛苦和经济方面造成高昂代价,而且当这些耐多药感染发展为广泛耐药结核病(XDR TB)时,不仅难以治疗,无论采用何种治疗方式,死亡率都很高。已证明抗精神病药物硫利达嗪(TZ)在体外和体内对敏感、耐多药和广泛耐药菌株具有广谱活性,已成功用于治愈由敏感和耐多药菌株引起的活动性结核病小鼠,并且在与三种广泛耐药结核病患者无反应的抗生素联合使用时,治愈了12例广泛耐药结核病患者中的10例。对于预后严重且预计会导致死亡的耐多药/广泛耐药结核病感染,已推荐使用结核分枝杆菌TZ进行“同情治疗”。这篇关于TZ活性及其治愈耐多药/广泛耐药结核病潜力的综述支持了这样一种观点,即这种抗精神病药物提供了“新用途”的专利机会。因此,申请专利的动机有望迅速将TZ推向耐多药/广泛耐药结核病治疗的前沿,所以,争取新专利有望有助于预防抗生素耐药结核病的新感染。

相似文献

1
Effective therapy with the neuroleptic thioridazine as an adjunct to second line of defence drugs, and the potential that thioridazine offers for new patents that cover a variety of "new uses".使用抗精神病药物硫利达嗪作为二线防御药物的有效疗法,以及硫利达嗪为涵盖各种“新用途”的新专利所提供的潜力。
Recent Pat Antiinfect Drug Discov. 2011 May;6(2):84-7. doi: 10.2174/157489111796064542.
2
Therapy Of XDR TB with thioridazine a drug beyond patent protection but eligible for patent "as new use".使用已过专利保护期但符合“新用途专利”条件的硫利达嗪治疗广泛耐药结核病。
Recent Pat Antiinfect Drug Discov. 2010 Jun;5(2):109-14. doi: 10.2174/157489110791233540.
3
It is anticipated that as is usually the case, financial motivation will move TZ from its current status “potential anti-MDR/XDR agent,” to one that will cure MDR and XDR TB. Foreword.正如通常情况所预期的那样,经济激励将推动替加环素从其当前“潜在抗多重耐药/广泛耐药药物”的地位,转变为能够治愈多重耐药和广泛耐药结核病的药物。前言。
Recent Pat Antiinfect Drug Discov. 2011 May;6(2):76. doi: 10.2174/157489111796064605.
4
Promising therapy of XDR-TB/MDR-TB with thioridazine an inhibitor of bacterial efflux pumps.用硫利达嗪(一种细菌外排泵抑制剂)治疗广泛耐药结核病/耐多药结核病的前景疗法。
Curr Drug Targets. 2008 Sep;9(9):816-9. doi: 10.2174/138945008785747798.
5
Mechanisms by which thioridazine in combination with antibiotics cures extensively drug-resistant infections of pulmonary tuberculosis.硫利达嗪与抗生素联合使用治愈广泛耐药性肺结核感染的机制。
In Vivo. 2014 Mar-Apr;28(2):267-71.
6
Thioridazine: an old neuroleptic effective against totally drug resistant tuberculosis.硫利达嗪:一种对完全耐药结核病有效的老一代抗精神病药物。
Acta Med Port. 2012 Mar-Apr;25(2):118-21. Epub 2012 Jun 25.
7
Thioridazine cures extensively drug-resistant tuberculosis (XDR-TB) and the need for global trials is now!噻氯匹定可治愈广泛耐药结核病(XDR-TB),现在就需要开展全球试验!
Int J Antimicrob Agents. 2010 Jun;35(6):524-6. doi: 10.1016/j.ijantimicag.2009.12.019. Epub 2010 Feb 25.
8
XDR-TB, what is it; how is it treated; and why is therapeutic failure so high?广泛耐药结核病是什么;如何治疗;以及为什么治疗失败率如此之高?
Recent Pat Antiinfect Drug Discov. 2011 May;6(2):77-83. doi: 10.2174/157489111796064641.
9
Targeting the human macrophage with combinations of drugs and inhibitors of Ca2+ and K+ transport to enhance the killing of intracellular multi-drug resistant Mycobacterium tuberculosis (MDR-TB)--a novel, patentable approach to limit the emergence of XDR-TB.通过药物与钙离子和钾离子转运抑制剂的组合靶向人类巨噬细胞,以增强对细胞内多药耐药结核分枝杆菌(MDR-TB)的杀伤作用——这是一种限制广泛耐药结核病(XDR-TB)出现的新颖且可申请专利的方法。
Recent Pat Antiinfect Drug Discov. 2011 May;6(2):110-7. doi: 10.2174/157489111796064524.
10
Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections.为什么硫利达嗪与抗生素联合使用能治愈广泛耐药结核分枝杆菌感染。
Int J Antimicrob Agents. 2012 May;39(5):376-80. doi: 10.1016/j.ijantimicag.2012.01.012. Epub 2012 Mar 23.

引用本文的文献

1
From multidrug- to extensively drug-resistant tuberculosis: upward trends as seen from a 15-year nationwide study.从耐多药结核病到广泛耐药结核病:15 年全国性研究观察到的上升趋势。
PLoS One. 2013 May 9;8(5):e63128. doi: 10.1371/journal.pone.0063128. Print 2013.
2
Exposure of chlorpromazine to 266 nm laser beam generates new species with antibacterial properties: contributions to development of a new process for drug discovery.氯丙嗪暴露于 266nm 激光束会产生具有抗菌特性的新物质:为新药发现过程的发展做出贡献。
PLoS One. 2013;8(2):e55767. doi: 10.1371/journal.pone.0055767. Epub 2013 Feb 6.
3
Evidence of significant synergism between antibiotics and the antipsychotic, antimicrobial drug flupenthixol.
抗生素与抗精神病药、抗菌药物氟奋乃静之间存在显著协同作用的证据。
Eur J Clin Microbiol Infect Dis. 2012 Jun;31(6):1243-50. doi: 10.1007/s10096-011-1435-3. Epub 2011 Oct 14.