Novel coatings releasing synergistic polyphenols promote vascular healing

新型涂层释放协同多酚促进血管愈合

• 批准号: 8716232
• 负责人: TAMMY R DUGAS
• 金额: $ 22.37万
• 依托单位: REQUISITE BIOMEDICAL, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8716232
• 关键词: Address; Americas; Angioplasty; Animal Model; Animals; Antiplatelet Drugs; Area; Arteries; Biological Factors; Blood Platelets; Blood Vessels; Blood coagulation; Blood flow; Cardiac; Cardiovascular Diseases; Cause of Death; Cell Proliferation; Clinical; Clinical Trials; Coagulation Process; Consultations; Coronary; Coronary artery; Data; Development; Devices; Disadvantaged; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Drug usage; Endothelial Cells; Endothelium; Event; FDA approved; Family suidae; Funding; Generations; Goals; Healed; Hyperplasia; Implant; Inflammation; Injury; Intervention; Left; Lesion; Letters; Licensing; Lower Extremity; Marketing; Medical; Medical Device; Metals; Modeling; Oryctolagus cuniculus; Outcome; Patients; Peripheral; Peripheral arterial disease; Pharmaceutical Preparations; Phase; Physicians; Poison; Procedures; Process; Property; Quercetin; Rattus; Research Design; Resveratrol; Risk; Rodent Model; Safety; Site; Small Business Technology Transfer Research; Smooth Muscle Myocytes; Solutions; Source; Staging; Stenosis; Stents; Testing; Thrombosis; Time; Tubular formation; United States; Validation; Wound Healing; artery occlusion; biomaterial compatibility; clinically relevant; commercial application; commercialization; graft failure; healing; high risk; human FRAP1 protein; implantation; improved; new technology; novel; phase 1 study; phase 2 study; polyphenol; prevent; public health relevance; red wine; research study; response; restenosis; vascular smooth muscle cell proliferation

PROJECT SUMMARY Cardiovascular disease (CVD) remains the number one cause of death in the U.S. Left untreated, CVD can result in the occlusion of key arteries that can precipitate a major cardiac event. Clinicians routinely correct arterial blockages mechanically using a balloon expansion of the lesioned area and placement of a metallic stent to help keep the arteries open. However, the overstretch of the vessel that takes place during the intervention is damaging to the artery wall. This damage often precipitates a re-narrowing of the artery (restenosis) due to the proliferation of smooth muscle cells within the vascular wall. Drug-eluting stents (DES) were developed to inhibit smooth muscle cell proliferation, but have the disadvantage that while keeping the arteries open, they also prevent the relining of the vessel wall with a functional endothelial cell layer. This requires that patients undergo long-term treatment with dual anti-platelet therapies in order to prevent rare, but often fatal late-term clotting events at the site of the implant. The applicant has developed a new coating for the endovascular drug delivery of synergistic natural products that prevent the negative responses to angioplasty treatment that promote artery re-narrowing. However, unlike the drugs currently used for stent coatings, these compounds have been shown to actively accelerate endothelial wound healing. Moreover, our preliminary data utilizing a rat model of stenting and angioplasty showed that DES coated with resveratrol and quercetin (RQ-DES) dramatically reduced restenosis, while at the same time, accelerated re-endothelialization to complete the healing process. The significance of these new RQ-DES is that by promoting vascular healing (i.e., re-endothelialization), their use in vascular interventions could reduce the need for dual anti-platelet therapies, as well as provide for safer long term outcomes. In this phase I proposal, the applicant will utilize an FDA-accepted, clinically relevant rabbit model to test whether the RQ-DES promotes re-endothelialization compared to a commercial stent device. Complementary studies using other company funding will test whether the RQ- DES also reduces the extent of restenosis. These studies will set the stage for a larger phase II project aimed at fully characterizing the safety and efficacy of our coatings for further commercialization. Our commercialization efforts will be aimed at the use of an RQ coating for diverse applications, including coronary artery and peripheral artery diseases, as well as other applications in which neointimal hyperplasia contributes to clinical complications, such as in arteriovenous graft failure.

项目摘要 心血管疾病（CVD）仍然是美国第一名死亡原因 未经治疗的CVD可能会导致关键动脉阻塞，从而导致主要心脏 事件。临床医生通常使用气球扩展机械地纠正动脉阻塞 病变区域和金属支架的放置，以帮助保持动脉开放。但是， 干预期间发生的船只的过度拉伸正在损害动脉壁。 由于增殖，这种损害通常会引起动脉（再狭窄）的重新分泌 血管壁中的平滑肌细胞。开发了毒品洗脱支架（DES） 抑制平滑肌细胞增殖，但有缺点，即保持 动脉开放，它们还防止了使用功能性内皮细胞的容器壁的雷神 层。这要求患者在双重抗血小板疗法中接受长期治疗 为了防止植入物部位的罕见但通常是致命的晚期凝血事件。 申请人开发了一种新的涂层，用于血管内药物的协同输送 防止对促进血管成形术治疗的负面反应的天然产品 动脉重新结尾。但是，与目前用于支架涂料的药物不同，这些 已证明化合物积极加速内皮伤口愈合。而且，我们的 利用大鼠支架和血管成形术模型的初步数据表明，DES与 白藜芦醇和槲皮素（RQ-DES）大大降低了再狭窄，同时， 加速重新皮层化以完成愈合过程。这些的意义 新的RQ-DES是通过促进血管愈合（即重新内皮化），它们在 血管干预措施可能会减少对双重抗血小板疗法的需求，并提供 为了更安全的长期结果。 在此阶段I建议中，申请人将利用FDA受到临床相关的兔子 与商业相比 支架设备。使用其他公司资金的补充研究将测试RQ-是否是否 DES还降低了再狭窄的程度。这些研究将为更大的II期奠定基础 旨在充分表征我们涂料的安全性和功效的项目 商业化。我们的商业化工作将用于使用RQ涂层 包括冠状动脉和周围动脉疾病在内的各种应用以及其他应用 新内膜增生导致临床并发症的应用，例如 动静脉移植衰竭。