WOUND HEALING WITH RHAMNOLIPIDS

用鼠李糖脂治疗伤口

• 批准号: 2424022
• 负责人: GORAN PILJAC
• 金额: $ 9.99万
• 依托单位: TAJCO, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2424022
• 关键词: bioreactors; burn therapy; burns; collagen; drug screening /evaluation; fibroblasts; glycolipids; high performance liquid chromatography; laboratory rat; protein purification; surfactant; wound healing

The ability to control would contraction is important in preventing disfiguring scarring in burn and trauma patients. Fibroblasts within the wound generate the mechanical forces that cause this contraction, and their interactions with various extracellular matrix components are thought to regulate this process. Rhamnolipids inhibit DNA synthesis and proliferation of different cell types including keratinocytes and fibroblasts both in vitro and in vivo. The drug is more effective in its inhibition of fibroblasts, ordinarily faster growing cells. Therefore, healing of wounds treated with rhamnolipd(s) would be somewhat slowed. During Phase I, we will determine the optimal concentration of rhamnolipid for topical treatment of wounds, to enable healing without contraction.. This will be accomplished assaying the drug in 2 in vitro would healing assays: fibroblast populated collagen lattice contraction assay, and the wounded monolayer assay for keratincyte migration. The drug will also be assayed in an in vivo rat burn would model. In addition, Phase I will allow the company to identify commercial suppliers and establish the cost effectiveness of the drug as compared to conventional treatments. Phase II efforts will then be directed at human trials at two multicenter facilities. Laboratory scale fermentation and purification of rhamnolipids or synthesis facilities will need to be developed to produce the compound for human trials in Phase II. PROPOSED COMMERCIAL APPLICATION: There are no drugs which can prevent contractures in healing burn or other wounds. Wound healing without contracture is one of the very important tasks in surgery. Aside from the cosmetic and functional value, this drug may be so important in abdominal and pelvic surgeries. Fibrous tissue formation could lead to death in these cases, because to ileus. Drugs capable to reduce scar formation have enormous market value.

控制子宫收缩的能力对于预防子宫内膜异位症 烧伤和创伤患者的毁容疤痕。 内成纤维细胞 伤口产生导致这种收缩的机械力， 它们与各种细胞外基质成分的相互作用 来调节这个过程。 鼠李糖脂抑制DNA合成 和不同细胞类型的增殖，包括角质形成细胞， 成纤维细胞在体外和体内。 这种药物在治疗 它抑制成纤维细胞，通常是生长较快的细胞。 因此，我们认为， 用rhamnolipd（s）治疗的伤口的愈合将有点 慢下来。 在第一阶段，我们将确定 用于局部治疗伤口的鼠李糖脂，以使愈合， 收缩 这将通过在2个体外试验中测定药物来实现 伤口愈合测定：成纤维细胞填充的胶原晶格收缩 测定，和用于角质细胞迁移的损伤单层测定。 还将在体内大鼠烧伤模型中测定药物。 在 此外，第一阶段将允许公司确定商业 供应商，并建立药物的成本效益比较 常规治疗。 第二阶段的工作将针对 在两个多中心机构进行的人体试验。 实验室规模 发酵和纯化鼠李糖脂或合成设施将 需要开发用于人体试验的化合物， 第二阶段。 建议的商业应用：没有药物可以 防止愈合烧伤或其他伤口时的挛缩。伤口愈合 无挛缩是外科的重要任务之一。 除了美容和功能价值，这种药物可能是如此 在腹部和盆腔手术中很重要。纤维组织形成 在这种情况下会导致死亡，因为肠梗阻药物能够 减少疤痕形成有巨大的市场价值。