Wound Healing Properties of a Non-Irritating Novel 9-cis Retinoid Acid Derivative

无刺激性新型 9-顺式视黄酸衍生物的伤口愈合特性

• 批准号: 7389442
• 负责人: William Paul Purcell
• 金额: $ 59.9万
• 依托单位: MOLECULAR DESIGN INTERNATIONAL, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-30 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7389442
• 关键词: Acids; Affect; Chronic; Clinic; Collagen; Development; Diabetes Mellitus; Drug usage; Goals; Grant; Healed; Human; Laboratories; Learning; Light; MDI 301; Modeling; Organ Culture Techniques; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Physiology; Pilot Projects; Property; Rattus; Research; Research Project Grants; Retinoids; Risk; Safety; Site; Skin; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Streptozocin; Structure; Topical agent; Topical application; Tretinoin; Ulcer; United States Food and Drug Administration; Work; Wound Healing; base; collagenase; commercialization; diabetic; diabetic rat; healing; improved; irritation; novel; prophylactic; skin irritation; success; wound

DESCRIPTION (provided by applicant): MDI 301 is a synthetic retinoid that is similar to all-trans retinoic acid (RA) in its ability to stimulate collagen synthesis and inhibit the major collagen-degrading enzymes in skin. A feature that distinguishes MDI 301 from RA is its lack of irritation when applied topically to skin. Past studies from our laboratory have shown that topical pretreatment of diabetic rats with RA improves the healing of subsequently-induced abrasion wounds. The recently completed Phase I studies of this SBIR grant demonstrated that MDI 301 also improves healing of abrasion wounds in diabetic rats. The Phase II studies build on this. The workplan for the Phase II studies contains three specific aims: First, using the same model of streptozotocin-induced diabetes in rats as used in the initial studies, we will determine the extent to which MDI 301 improves wound-healing in the skin. Second, using organ cultures of human skin obtained from diabetic subjects (skin from both at-risk and non-at-risk sites) we will determine the extent to which MDI 301 affects changes in physiology of human diabetic skin that contribute to successful wound healing. Finally, in aim three, we will continue the safety profiling of MDI 301 necessary for FDA approval. The overall goal of the proposed studies is to determine if topical pretreatment of skin with MDI 301 will, like RA itself, improve healing of subsequently-induced wounds but do so without provoking irritation. If it can be shown that MDI 301 is as effective as RA but without the negative consequence seen with RA, it will provide a better agent for development as a chronic wound preventative.

描述（由申请人提供）：MDI 301是一种合成类维生素A，在刺激胶原蛋白合成和抑制皮肤中主要胶原蛋白降解酶的能力方面与全反式维甲酸（RA）相似。将MDI 301与RA区分开的一个特征是其在局部应用于皮肤时没有刺激性。我们实验室过去的研究表明，用RA局部预处理糖尿病大鼠可改善非自愿性磨损伤口的愈合。最近完成的SBIR资助的I期研究表明，MDI 301还可改善糖尿病大鼠擦伤伤口的愈合。第二阶段的研究是在此基础上进行的。II期研究的工作计划包含三个具体目标：首先，使用与初始研究中使用的相同的链脲佐菌素诱导的大鼠糖尿病模型，我们将确定MDI 301改善皮肤伤口愈合的程度。其次，使用从糖尿病受试者获得的人皮肤（来自风险和非风险部位的皮肤）的器官培养物，我们将确定MDI 301影响人糖尿病皮肤的生理学变化的程度，所述生理学变化有助于成功的伤口愈合。最后，在目标三中，我们将继续进行FDA批准所需的MDI 301安全性分析。 拟议研究的总体目标是确定用MDI 301局部预处理皮肤是否会像RA本身一样改善非自愿诱导伤口的愈合，但不会引起刺激。如果可以证明MDI 301与RA一样有效，但没有RA所见的负面后果，则它将提供更好的试剂用于开发作为慢性伤口预防剂。