PHOTODYNAMIC TREATMENT OF BENIGN UTERINE DISEASE

描述：拟议工作的长期目标是开发一种新的、 基于光动力学的子宫良性疾病微创治疗 治疗(PDT)。最终，子宫光动力疗法可能会对 妇女保健及其相关费用，因为它将提供 传统外科和内科的廉价门诊替代方案 功能性子宫出血(DUB)的治疗技术及改进 子宫腺肌病(AM)相关症状。在过去的六年里，我们有 完成了许多动物、人体和模型研究，这些研究帮助我们 了解实现不可逆子宫内膜固有的复杂性 PDT时消融(EA)。我们现在提出一项重大的新努力，它建立在 这一基础和进一步表征了光和药物剂量学如何 参数影响临床结果。具体目标包括：1) 构建、表征和优化一种新型的、 微创宫内光线探头(IULP)；2)完成I/II期 并开始使用ALA进行第三阶段人体临床试验；3)测试有限的 动物模型中新致敏剂的数量；以及4)评估 有限数量新化合物的药代动力学、安全性和有效性 在人类身上。

DESCRIPTION: The long-term goal of the proposed work is to develop a new, minimally-invasive treatment of benign uterine disease based on Photodynamic Therapy (PDT). Eventually, uterine PDT may have a significant impact on women's health care and its associated costs because it will provide an inexpensive, outpatient alternative to conventional surgical and medical techniques for treating dysfunctional uterine bleeding (DUB) and improving adenomyosis (AM)-related symptoms. During the past six years we have completed a number of animal, human and modeling studies that have helped us understand the complexity inherent to achieving irreversible endometrial ablation (EA) during PDT. We now propose a major new effort which builds on this foundation and further characterizes how light and drug dosimetry parameters affect clinical outcome. Specific aims include: 1) constructing, characterizing and optimizing performance of a novel, minimally-invasive intrauterine light probe (IULP); 2) completing Phase I/II and beginning Phase III human clinical trials with ALA; 3) testing a limited number of new sensitizers in animal models; and 4) evaluating pharmacokinetics, safety and efficacy of a limited number of new compounds in humans.