Replaceable Long Term Implanted Glucose Sensor

 描述(申请人提供)：糖尿病是一个主要的医疗保健问题，已经达到了危机的程度。这种疾病占美国国民医疗保健总支出的14%，造成了宝贵的人力资源的无数损失，迫切需要新的治疗方法。虽然血糖监测是糖尿病所有治疗方法的核心，但目前的“指棒”方法和短期的经皮针状传感器对许多潜在用户来说是不受欢迎的，限制了它们的应用。迫切需要一种新的、更容易被接受的葡萄糖传感器，它可以指导胰岛素剂量，警告低血糖，并作为实用人工胰腺的缺失组件。我们开发了一种新的、完全植入的葡萄糖传感器和无线遥测，用于长期植入皮下组织。在对正常和糖尿病猪的研究中，我们总共有31年的装置累积植入经验，其中17个装置保持功能超过一年，一个植入物功能520天(科学。翻译过来的。地中海医院。2，42ra53,2010)。在最初的人体试验中，该传感器还成功工作了六个月。该传感器采用了一种独特的设计，通过差动酶电极检测原理来监测葡萄糖，克服了植入物由身体包裹的局限性。与其他血糖传感器相比，这种传感器具有根本优势：用户不需要频繁地重新校准或更换传感器，从而使连续的血糖监测以及潜在的人工胰腺更容易为普通糖尿病公众所接受。尽管传感器遥测系统至少可以工作一年，计划中的改进可能会进一步延长其寿命，但该设备最终将不得不更换。非常希望尽可能重复使用相同的植入部位，而不是在一生中创建多个新的植入部位。这里要解决的问题是：植入物部位可以重复使用吗？涉及哪些组织反应机制？需要检验的假设是“植入部位是可重复使用的。”先前的研究表明，植入部位在8周内完全稳定，这表明在猪身上加速的12周更换测试周期可以对应于1至2年的临床更换周期。在这个第一阶段的项目中，将在每两头猪身上植入四个传感器遥测单元，并进行每周一次的血糖挑战。设备将每12周更换一次，广泛的统计分析将确定是否可以在现场继续进行有效的监测。将评估组织对葡萄糖和氧气的渗透性，进行广泛的组织学检查，并构建质量传递模型。如果成功，这些研究将为终生连续监测血糖提供基础，对糖尿病患者的干扰最小。

 DESCRIPTION (provided by applicant): Diabetes is a major health care problem that has reached crisis proportions. The disease accounts for >14% of total national health care expenditures in the US and untold losses of precious human resources, and new therapies are urgently needed. Although glucose monitoring is central to all therapies for diabetes, present "fingerstick" methods and short-term percutaneous needle-like sensors are objectionable to many potential users, limiting their application. A new, more acceptable glucose sensor is urgently needed that could direct insulin dosing, warn of hypoglycemia, and serve as the missing component of a practical artificial pancreas. We have developed a new, fully implanted glucose sensor and wireless telemetry for long-term implantation in subcutaneous tissues. In studies with normal and diabetic pigs, we have a total of 31 cumulative device-years of implant experience, with 17 of the devices remaining functional for more than one year, and one implant functioning for 520 days (Sci. Trans. Med. 2, 42ra53, 2010). The sensor has also functioned successfully for six months in an initial human trial. The sensor incorporates a unique design in which glucose is monitored via a differential enzyme electrode detection principle that overcomes the limitations of implant encapsulation by the body. This sensor has fundamental advantages over other glucose sensors: users don't need to recalibrate or replace the sensor frequently, making continuous glucose monitoring and potentially the artificial pancreas much more acceptable to the general diabetic public. Although the sensor-telemetry system can function for at least one year and planned improvements may further extend its lifetime, the device will eventually have to be replaced. It is highly desirable to reuse the same implant site i possible, rather than creating multiple new implant sites over a lifetime. The questions to be addressed here are: Can an implant site be reused? What tissue response mechanisms are involved? The hypothesis to be tested is "The implant site is reusuable." Previous studies showed that implant sites have fully stabilized within 8 weeks, indicating that an accelerated 12-week replacement test cycle in the pigs can correspond to a 1 to 2-year clinical replacement cycle. In this Phase I project, four sensor-telemetry units will be implanted in each of two pigs, and weekly glucose challenges will be performed. Devices will be exchanged every 12 weeks, and an extensive statistical analysis will determine whether effective monitoring can continue at the sites. Tissue permeability to glucose and oxygen will be assessed, extensive histologic examination will be performed, and mass transfer models will be constructed. If successful, these studies will provide a foundation for continuous glucose monitoring over a lifetime, with minimal obtrusiveness to people with diabetes.