用于治疗胃食管反流病的食管下括约肌电刺激系统设计与实验研究

发布时间：2018-11-10 12:19

【摘要】：胃食管反流病(Gastroesophageal Reflux Disease,GERD)是指胃内容物反流入食管,引起不适症状和(或)并发症的一种疾病。全世界范围内,大约有2.5亿个GERD患者。随着GERD的发病率逐年上升,社会医疗负担越来越重,GERD的合理诊治已成为全世界关注和研究的热点。而传统的药物治疗存在治标不治本的问题,停药后症状复发,患者不得不长期使用药物。手术治疗则创伤大,术后会有吞咽困难、腹胀和腹泻等并发症。食管下括约肌(Lower esophageal sphincter,LES)电刺激治疗方法为难治性GERD的治疗提供了一种新方法。国外基于LES电刺激治疗方法推出了 EndoStim植入式LES电刺激系统,并进行了大量的临床实验研究。而国内相关研究较少,目前尚无可应用于临床的植入式LES电刺激系统。为了打破国外产品的垄断,填补国内该技术领域的空白,本文研究设计了一种无线供能的LES电刺激系统。该系统由体外无线控制器、无线能量传输模块和植入式LES电刺激器组成。系统在实现植入式LES电刺激功能的基础上,实现了无线能量传输功能,解决了 EndoStim系统无法外部供能的问题。本论文的研究内容主要包括:1)无线供能的LES电刺激系统方案设计:在分析讨论用于治疗GERD的LES电刺激系统的功能需求与设计目标基础上,确定了无线供能的LES电刺激系统的设计方案。根据电磁波穿透深度和电磁辐射对人体的影响,选用4MHz作为无线能量传输的工作频率。还讨论了系统集成与封装方案,为系统的模块化设计和生物相容性封装打下了基础。2)体外无线控制器设计:分析讨论了基于低功耗蓝牙技术(Bluetooth Low Energy,BLE)的体外无线控制器的设计方案与工作原理。该控制器主要包括CC2541模块、USB转串口电路、锂电池充电电路和电源管理电路。其中,CC2541模块采用了与植入式LES电刺激器相同的定制电路模块进行设计,USB转串口电路采用CH340G芯片实现与上位机的串口通信。锂电池充电电路则采用LTC4054-4.2芯片,充电电流设置为500mA。电源管理电路采用了 RT9013-33GB线性稳压电路。在完成了体外控制器硬件设计的基础上,从CC2541开发、上位机程序开发和手机蓝牙控制植入式LES电刺激器三方面进行了系统的软件设计。CC2541开发过程中所采用的协议栈版本为TI的BLE-CC254x-1.3.2,开发环境为IAR 8051。上位机程序开发采用C#语言进行编程,所使用的开发环境为Visual Studio 2012。此外,使用LightBlue手机蓝牙APP实现了对植入式LES电刺激器的控制。3)无线能量传输模块设计:在分析讨论了无线能量传输的理论基础和线圈设计方案后,确定了无线能量传输模块的设计方案。该模块包括体外能量发射电路和体内能量接收电路。其中,体外能量发射电路由线性稳压器、有源晶振电路和E类功率放大器组成。其功能是将体外电源的直流电压变换为交流电压,并加载到发射线圈上向体内传输能量。体内能量接收电路则采用桥式整流、电容滤波和降压-升压型电荷泵稳压器LTC3245,将接收线圈上耦合得到的交流电压变换为直流电压。4)植入式LES电刺激器设计:分析讨论了植入式LES电刺激器的设计方案与工作原理。设计了包含能量接收电路、电源管理电路、CC2541模块、DAC电路和压控恒流刺激电路的植入式LES电刺激器。电源管理电路分别采用RT9013-33GB、MAX1595EUA50+和MAX865EUA芯片将3.7～5V的输入电压转换为CC2541模块、DAC电路和压控恒流刺激电路的供电电压。DAC电路采用MAX5705芯片输出可控电压,控制压控恒流刺激电路产生相应大小的电流刺激脉冲。压控恒流刺激电路采用OPA4192芯片产生0～8mA的电流刺激脉冲。5)植入式LES电刺激系统测试与实验研究:使用美国道康宁公司的Sylgard 184型聚二甲基硅氧烷对电极导线和植入式LES电刺激器进行了封装,并使用ABS塑料壳体封装了体外控制器。完成植入式LES电刺激系统的封装后,对系统的无线能量传输功能进行了测试,并给出了空气、0.9%盐水和猪皮3种介质条件下系统正常工作的位置失配容限指标。在此基础上,以家兔为实验对象开展了 GERD造模实验、水灌注式食管测压实验和LES电刺激实验。实验结果表明:本文研究设计的植入式LES电刺激系统可以增强(恢复)造模后实验动物的LES压力,对于治疗GERD具有可行性。
[Abstract]:Gastroesophageal reflux disease (GERD) is a disease of the stomach contents to flow into the esophagus, causing discomfort and/ or complications. There are about 250 million GERD patients worldwide. As the incidence of GERD is increasing year by year, the burden of social medical care is getting more and more, and the rational diagnosis and treatment of GERD has become the focus of attention and research worldwide. and the traditional medicine treatment has the problems of no treatment and treatment, and the symptoms of the drug withdrawal after the drug withdrawal are recurrent, and the patient has to use the medicine for a long time. The surgical treatment is large, and there are complications such as dysphagia, abdominal distention, and diarrhea after operation. The electrical stimulation of the lower esophageal sphincter (LES) provides a new method for the treatment of refractory GERD. The EndoStim implantable LES electrical stimulation system was introduced based on LES electrical stimulation therapy in foreign countries, and a large number of clinical trials were conducted. At present, there are no implantable LES electrical stimulation systems that can be applied to clinical practice. In order to break the monopoly of foreign products and to fill the gap in the domestic technology field, a wireless power-powered LES electric stimulation system is designed. The system consists of an in-vitro wireless controller, a wireless energy transmission module and an implantable LES electric stimulator. The system realizes the function of wireless energy transmission on the basis of realizing the function of the electric stimulation of the implanted LES, and solves the problem that the EndoStim system cannot be externally supplied. The research contents of this paper mainly include: 1) the scheme design of LES electric stimulation system for wireless power supply: based on the analysis and discussion on the function requirement and design goal of LES electric stimulation system for treating GERD, the design scheme of LES electric stimulation system for wireless power supply is determined. according to the penetration depth of the electromagnetic wave and the influence of the electromagnetic radiation on the human body, 4MHz is selected as the operating frequency of the wireless energy transmission. This paper also discusses the system integration and packaging scheme, and lays a foundation for the modular design and the biocompatibility package of the system. 2) In-vitro wireless controller design: the design and working principle of the in-vitro wireless controller based on Bluetooth Low Energy (BLE) are analyzed and discussed. The controller mainly comprises a CC2541 module, a USB rotating serial port circuit, a lithium battery charging circuit and a power supply management circuit. The CC2541 module is designed with the same custom circuit module as the implantable LES electrical stimulator. The serial port of the USB-to-serial port adopts the CH340G chip to realize the serial communication with the upper computer. The lithium battery charging circuit adopts the LTC4054-4.2 chip, and the charging current is set to 500mA. The power management circuit adopts the RT9013-33GB linear voltage stabilizing circuit. On the basis of completing the hardware design of the in-vitro controller, the software design of the system is carried out from the development of CC2541, the development of the host computer and the Bluetooth control of the mobile phone. The protocol stack used in the development of the CC2541 is the BLE-CC254x-1. 3.2 of TI, and the development environment is IAR 8051. The host computer program is programmed with C # language, and the development environment used is Visual Studio 2012. In addition, the control of the implantable LES electric stimulator is realized by using the LightBlue mobile phone Bluetooth APP. 3) Design of the wireless energy transmission module: After the theoretical basis and the coil design scheme of the wireless energy transmission are analyzed, the design scheme of the wireless energy transmission module is determined. The module includes an in vitro energy emitting circuit and an in-vivo energy receiving circuit. wherein the in-vitro energy transmitting circuit consists of a linear regulator, an active crystal oscillator circuit and an E-class power amplifier. The function of the invention is to convert the direct current voltage of the in-vitro power supply into an alternating current voltage and to load the external power source into the transmission coil to transmit energy to the body. the in-vivo energy receiving circuit adopts a bridge type rectification, a capacitor filtering and a step-down-boost type charge pump voltage regulator LTC3245 to convert the alternating current voltage coupled on the receiving coil into a direct current voltage. The design and working principle of the implantable LES electric stimulator are discussed. An implantable LES electrical stimulator is designed that includes an energy receiving circuit, a power management circuit, a CC2541 module, a DAC circuit, and a voltage-controlled constant current stimulation circuit. The power management circuit adopts the RT9013-33GB, the MAX1595EUA50 + and the MAX865EUA chip to convert the input voltage of 3.7 to 5V to the power supply voltage of the CC2541 module, the DAC circuit and the voltage-controlled constant current stimulation circuit. The DAC circuit adopts the MAX5705 chip to output the controllable voltage, and controls the voltage-controlled constant current stimulation circuit to generate the current stimulation pulse of the corresponding size. The voltage-controlled constant current stimulation circuit uses the OPA4192 chip to generate a current-stimulating pulse of 0-8mA. and an in vitro controller is packaged using an abs plastic housing. After the encapsulation of the implantable LES electrical stimulation system, the wireless energy transmission function of the system was tested, and the position-mismatch tolerance index of the system's normal operation under the condition of air, 0.9% saline and 3 medium conditions of the pigskin was also given. On the basis of this, the experiment of GERD model, the experiment of water-filled esophagus and the electric stimulation of LES were carried out in rabbits. The experimental results show that the LES pressure of the experimental animal can be enhanced (recovered) by the implanted LES electrical stimulation system designed in this paper, and it is feasible to treat GERD.
【学位授予单位】：东南大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R571

【相似文献】