Amaral Leonard, Viveiros Miguel, Molnar Joseph, Kristiansen Jette E
Grupo de Micobactérias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Portugal.
Recent Pat Antiinfect Drug Discov. 2011 May;6(2):84-7. doi: 10.2174/157489111796064542.
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.
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。