An Intraperitoneal Insulin Delivery System for Management of Type 1 Diabetes

摘要 Perikinic公司用于1型糖尿病(T1D)治疗的腹膜(IP)胰岛素给药系统利用 创新的植入式端口导管系统，通过专有的外部输液器进入，提供安全的 严格控制血糖的有效手段。对于160万患有T1D的美国人来说，现代技术 进展改善了血糖感应和胰岛素输送，然而，实现严格的血糖控制仍然存在。 很有挑战性。IP腔为T1D患者的胰岛素输送提供了一个优越的位置。IP胰岛素递送 通过在门静脉系统中提供更高的胰岛素浓度，更好地模拟生理递送，使 被肝脏快速吸收，对血糖紊乱和降低低血糖的反应更有效 剧集。到目前为止开发的持续IP胰岛素输注(CIPII)系统显示出戏剧性的 血糖调节的改善，但不幸的是，受到导管阻塞、感染和美观的影响 毁容。目前没有FDA批准的CIPII系统在美国上市。提高了安全性和 IP胰岛素设备的临床应用将使血糖控制的更好选择在 更严密的监控范围。Perikinic(PK)已经开发出PK胰岛素输送管道(IDC)，一种可植入的 由专有的外部输液器接入的端口-导管系统，用于IP胰岛素输送。在我们的第一阶段 通过等效性研究，我们建立了该系统通过体外流动表征、植入的可行性 生存能力和机械完整性测试。这项提议的总体目标是证明PK IDC可以安全有效地在T1D动物模型中提供基础和团注胰岛素。在具体目标1中，我们将 在工作台上评估胰岛素的稳定性，以确保注射的胰岛素不会受到设备的不利影响 或交付方式。在具体目标2中，我们将进行一项先导性动物研究，以验证安全性、有效性和临床疗效。 PK IDC的实用程序。成功完成这些目标将使该设备能够用于支持IDE的研究， 最终，De novo 510(K)成为第一个使用皮下端口减少胰岛素注射的IP载体 感染和提高生活质量。

ABSTRACT Perikinetics’ intraperitoneal (IP) insulin delivery system for the management of Type 1 diabetes (T1D) utilizes an innovative implantable port-catheter system accessed by a proprietary external infusion set to provide a safe and effective means of tight glycemic control. For the 1.6 million Americans living with T1D, modern technological advances have improved glucose sensing and insulin delivery, however, achieving tight glycemic control remains challenging. The IP cavity presents a superior location for insulin delivery for T1D patients. IP insulin delivery better mimics physiological delivery by providing a higher insulin concentration in the portal system, enabling rapid absorption by the liver, and a more effective response to glycemic disturbances and reduced hypoglycemic episodes. Continuous IP insulin infusion (CIPII) systems developed to date have demonstrated dramatic improvement in glucose regulation but, unfortunately, suffer from catheter obstruction, infection, and aesthetic disfigurement. No FDA approved CIPII systems are currently available in the U.S. Improving the safety and clinical utility of IP insulin devices would enable commercialization of a superior option for glycemic control within a tighter monitoring range. Perikinetics (PK) has developed the PK Insulin Delivery Conduit (IDC), an implantable port-catheter system accessed by a proprietary external infusion set for IP insulin delivery. In our Phase I equivalent research studies, we established feasibility of the system through in vitro flow characterization, implant viability, and mechanical integrity testing. The overall objective of this proposal is to demonstrate that the PK IDC can safely and effectively deliver basal and bolus insulin in a T1D animal model. In Specific Aim 1, we will assess insulin stability on the bench to ensure that injected insulin will not be adversely affected by the device or delivery method. In Specific Aim 2, we will conduct a pilot animal study to validate safety, efficacy, and clinical utility of the PK IDC. Successful completion of these aims will position the device for IDE-enabling studies and, ultimately, de novo 510(k) clearance as the first IP insulin delivery vehicle using a subcutaneous port to reduce infection and improve quality of life.