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治疗性液体混合物和制剂在结核病治疗中的应用。

Insights into therapeutic liquid mixtures and formulations towards tuberculosis therapy.

机构信息

LAQV, REQUIMTE, Chemistry Department of NOVA School of Science and Technology, Caparica, Portugal.

Host-Pathogen Interactions Unit, Research Institute for Medicines, iMed-ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal.

出版信息

Int J Pharm. 2023 Apr 25;637:122862. doi: 10.1016/j.ijpharm.2023.122862. Epub 2023 Mar 23.

Abstract

Therapeutic liquid mixtures, as deep eutectic systems, are considered a sustainable strategy that can be useful for the modification and enhancement of the pharmacokinetics and pharmacodynamics of different active ingredients. In this study, we assessed the stability and antibacterial activity of therapeutic liquid formulations prepared with anti-tuberculosis drugs. Tuberculosis therapy presents various pitfalls related, for example, to the administration of prolonged regimens of multiple drugs, different severe adverse effects, low compliance of the patient to treatment and the development of drug resistance. During this study, it was possible to assess the physicochemical stability of the formulations for 6 months, by polarized optical microscopy, H NMR and FTIR-ATR. Furthermore, the mixtures present an antibacterial effect against a drug-susceptible Mycobacterium tuberculosis strain (H37Rv). This was particularly evident for the mixtures with ethambutol incorporated, making them interesting to pursue with further studies and evaluation of clinical applicability. Upon infection, it was also observed that a single and higher dose appears to be more effective than lower separate doses, which could allow the production of patient-friendly formulations.

摘要

治疗性液体混合物,如深共晶溶剂,被认为是一种可持续的策略,可用于修饰和增强不同活性成分的药代动力学和药效学。在这项研究中,我们评估了用抗结核药物制备的治疗性液体配方的稳定性和抗菌活性。结核病治疗存在各种问题,例如,需要长时间使用多种药物、严重不良反应不同、患者对治疗的依从性低以及耐药性的产生。在这项研究中,通过偏光显微镜、H NMR 和 FTIR-ATR,我们能够评估配方在 6 个月内的物理化学稳定性。此外,这些混合物对药敏结核分枝杆菌菌株(H37Rv)具有抗菌作用。对于含有乙胺丁醇的混合物,这一点尤为明显,这使得它们具有进一步研究和评估临床适用性的潜力。在感染后,我们还观察到单剂量和高剂量似乎比低剂量更有效,这可能允许生产适合患者的制剂。

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