New stimulator for chronic wound healing-Phase II

描述(申请人提供)：随着年龄的增长和肥胖的加剧，我们的社会越来越容易受到慢性创伤的影响。尽管如此，目前还没有高效、廉价和易于应用的伤口愈合药物。在这里，我们发起了这样一种药物的开发。在第一阶段中，我们展示了我们实验室从一种用于治疗慢性伤口的药用植物中分离出来的胶原蛋白、成纤维细胞和血管刺激化合物具有良好的伤口愈合活性。该化合物的生物活性已在愈合受损的糖尿病小鼠和受伤的人皮肤移植/小鼠嵌合体中得到验证。此外，初步的安全性研究表明，该产品的局部应用可能是安全的。在这个第二阶段的项目中，我们建议a)利用啮齿动物和兔的伤口愈合模型来建立这种化合物的最佳生物活性剂量；b)在啮齿动物、兔子和猪身上证明这种化合物比目前临床上使用的伤口愈合处方药更有效；c)证明这种候选药物不仅能刺激伤口愈合，而且能产生更大的愈合组织的抗张强度；d)在一系列PK/ADME/毒理学试验中验证其安全性。总之，拟议的实验应该证实这种新型伤口愈合化合物的治疗潜力，并推动其向IND应用的发展。

DESCRIPTION (provided by applicant): Our society becomes increasingly vulnerable to chronic wounds as we age and become more obese. Despite that, efficient, inexpensive and simple-to-apply wound-healing drugs are presently unavailable. Here, we initiated the development of such a drug. In Phase I we demonstrated the superior wound-healing activity of a collagen-, fibroblast- and angiostimulatory compound isolated in our lab from a medicinal plant used for chronic wound treatment. The bioactivity of this compound has been validated in healing-impaired diabetic mice and in wounded human skin graft/mouse chimeras. Furthermore, the preliminary safety studies showed that the topical application of this product may be safe. In this Phase II project we propose to a) establish the optimal bioactive dose of this compound using rodent and rabbit wound-healing models; b) demonstrate in rodents, rabbits and swines that this compound is more efficient than the wound-healing prescription drug currently used in clinic; c) demonstrate that this drug- candidate not only does stimulate wound healing, but also results in greater tensile strength of the healed tissue, d) validate its safety in a series of PK/ADME/Toxicology tests. Together, the proposed experiments should confirm the therapeutic potential of this novel wound-healing compound and advance its development towards the IND application.