Observer-Based Impulsive Controller Design for Treatment of Hepatitis C Disease,Industrial & Engineering Chemistry Research

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Observer-Based Impulsive Controller Design for Treatment of Hepatitis C Disease
Industrial & Engineering Chemistry Research ( IF 3.8 ) Pub Date : 2020-09-27 , DOI: 10.1021/acs.iecr.0c04058
Sahar Zeinali ₁ , Mohammad Shahrokhi ₁ , Asier Ibeas _{2,

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Affiliation

In this study, an impulsive state feedback controller has been proposed for the treatment of hepatitis-C-infected patients under Pegylated-Interferon (PEG-IFN-α_2b) therapy. The Neumann model has been utilized as the representative of the hepatitis C virus (HCV) dynamics. In order to consider the drug efficacy variation between injections, the pharmacokinetics/pharmacodynamics (PK/PD) equations have been included in the model. The impulsive nature of the drug injection also has been considered in the disease dynamics. In the proposed treatment method, the drug dose limitation has been addressed as an input nonlinearity. The asymptotical stability of the control method under the impulsive nature of the drug administration and its limited dose amount have been shown through the use of a combination of a heuristic approach and the Lyapunov theory. For the implementation of the control strategy, all system states should be available, while only the viral load is measured at certain discrete times. In order to solve this problem, a nonlinear impulsive Luenberger-like observer has been designed to estimate the unknown states. Finally, the effectiveness of the controller under impulsive and limited input with and without the observer has been investigated via simulation study. The results show that, in both cases, the treatment objective has been achieved and the viral load decreases to its desired value. The observer also has good performance, and the estimated states converge to their actual values.

中文翻译：

基于观察者的丙型肝炎脉冲控制器设计

在这项研究中，已提出了一种脉冲状态反馈控制器，用于在聚乙二醇化干扰素（PEG-IFN- _α2b）治疗。诺伊曼模型已被用作丙型肝炎病毒（HCV）动态的代表。为了考虑注射之间的药物功效差异，模型中包括了药代动力学/药效学（PK / PD）方程。在疾病动力学中也已经考虑了药物注射的冲动性质。在提出的治疗方法中，药物剂量限制已被解决为输入非线性。通过使用启发式方法和李雅普诺夫理论的结合，已经证明了控制方法在药物给药的脉冲性质下的无症状稳定性及其有限的剂量。为了实施控制策略，所有系统状态都应可用，而在某些离散时间仅测量病毒载量。为了解决这个问题，已经设计了一种非线性的类似于Luenberger的脉冲观测器来估计未知状态。最后，通过仿真研究了在有观察者和无观察者的情况下，在脉冲和有限输入下控制器的有效性。结果表明，在两种情况下，均已达到治疗目的，病毒载量降至所需值。观察者也具有良好的性能，并且估计状态收敛到其实际值。达到了治疗目的，病毒载量降至所需值。观察者也具有良好的性能，并且估计状态收敛到其实际值。达到了治疗目的，病毒载量降至所需值。观察者也具有良好的性能，并且估计状态收敛到其实际值。

更新日期：2020-10-29

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