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脓毒症的治疗干预:当前及预期的药物制剂

Therapeutic interventions in sepsis: current and anticipated pharmacological agents.

作者信息

Shukla Prashant, Rao G Madhava, Pandey Gitu, Sharma Shweta, Mittapelly Naresh, Shegokar Ranjita, Mishra Prabhat Ranjan

机构信息

Pharmaceutics Division, Preclinical South PCS 002/011, CSIR - Central Drug Research Institute, Lucknow, India.

出版信息

Br J Pharmacol. 2014 Nov;171(22):5011-31. doi: 10.1111/bph.12829. Epub 2014 Sep 5.

Abstract

Sepsis is a clinical syndrome characterized by a multisystem response to a pathogenic assault due to underlying infection that involves a combination of interconnected biochemical, cellular and organ-organ interactive networks. After the withdrawal of recombinant human-activated protein C (rAPC), researchers and physicians have continued to search for new therapeutic approaches and targets against sepsis, effective in both hypo- and hyperinflammatory states. Currently, statins are being evaluated as a viable option in clinical trials. Many agents that have shown favourable results in experimental sepsis are not clinically effective or have not been clinically evaluated. Apart from developing new therapeutic molecules, there is great scope for for developing a variety of drug delivery strategies, such as nanoparticulate carriers and phospholipid-based systems. These nanoparticulate carriers neutralize intracorporeal LPS as well as deliver therapeutic agents to targeted tissues and subcellular locations. Here, we review and critically discuss the present status and new experimental and clinical approaches for therapeutic intervention in sepsis.

摘要

脓毒症是一种临床综合征,其特征为因潜在感染引发的对致病性攻击的多系统反应,涉及相互关联的生化、细胞和器官 - 器官交互网络的组合。在重组人活化蛋白C(rAPC)撤市后,研究人员和医生一直在继续寻找针对脓毒症的新治疗方法和靶点,这些方法在低炎症和高炎症状态下均有效。目前,他汀类药物正在临床试验中作为一种可行的选择进行评估。许多在实验性脓毒症中显示出良好效果的药物在临床上无效或尚未进行临床评估。除了开发新的治疗分子外,开发各种药物递送策略(如纳米颗粒载体和基于磷脂的系统)还有很大空间。这些纳米颗粒载体可中和体内脂多糖,并将治疗剂递送至靶向组织和亚细胞位置。在此,我们综述并批判性地讨论脓毒症治疗干预的现状以及新的实验和临床方法。

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