New stimulator for chronic wound healing-Phase II

新型慢性伤口愈合刺激器-第二阶段

• 批准号: 7233648
• 负责人: HUI ZHAO
• 金额: $ 48.79万
• 依托单位: SUNNY BIODISCOVERY, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7233648
• 关键词: Advanced Development; Age; Angelica sinensis; Animal Model; Animals; Architecture; Becaplermin; Biodistribution; Chimera organism; Chronic; Clinic; Clinical Trials; Collagen; Complement; Condition; Cutaneous; Data; Dermal; Development; Diabetic mouse; Documentation; Dose; Drug Kinetics; Drug Prescriptions; Ear; Endothelial Cells; Excision; Family suidae; Fibroblasts; Growth; Guidelines; Healed; Human; Impaired wound healing; Ischemia; Measures; Medicinal Plants; Modeling; Molecular; Molecular Structure; Mus; Nitric Oxide; Non-Rodent Model; Obesity; Oryctolagus cuniculus; Pharmaceutical Preparations; Phase; Plants; Rat-1; Rodent; Rodent Model; Safety; Series; Skin; Skin graft; Societies; Surgical incisions; Sus scrofa; Tensile Strength; Testing; Therapeutic; Therapeutic Index; Thick; Tissues; Topical application; Toxic effect; Toxicology; Ulcer; United States Food and Drug Administration; Wound Healing; base; design; diabetic; drug development; healing; mouse model; novel; pre-clinical; preclinical study; prescription document; prescription procedure; research study; response; small molecule; subcutaneous; wound

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.

描述（由申请人提供）：随着年龄的增长和肥胖程度的增加，我们的社会变得越来越容易受到慢性伤口的影响。尽管如此，目前还没有有效、廉价且易于使用的伤口愈合药物。在这里，我们开始了这种药物的开发。在第一阶段，我们展示了我们实验室从用于慢性伤口治疗的药用植物中分离出的胶原蛋白、成纤维细胞和血管刺激化合物的卓越伤口愈合活性。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类皮肤移植/小鼠嵌合体中得到验证。此外，初步安全性研究表明该产品的局部应用可能是安全的。在这个二期项目中，我们建议 a) 使用啮齿动物和兔子伤口愈合模型确定该化合物的最佳生物活性剂量； b) 在啮齿动物、兔子和猪身上证明该化合物比目前临床上使用的伤口愈合处方药更有效； c) 证明该候选药物不仅能刺激伤口愈合，还能使愈合组织具有更大的拉伸强度，d) 在一系列 PK/ADME/毒理学测试中验证其安全性。总之，所提出的实验应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。