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: 7615100
• 负责人: William Paul Purcell
• 金额: $ 59.77万
• 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/7615100
• 关键词: Acids; Affect; Chronic; Clinic; Collagen; Development; Diabetes Mellitus; Drug usage; Goals; Grant; Healed; Human; Infection; Inflammation; Laboratories; Learning; Light; Modeling; Organ Culture Techniques; Patients; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Physiology; Pilot Projects; Process; Property; Public Health; Rattus; Research; Research Project Grants; Retinoids; Risk; Safety; Site; Skin; Small Business Innovation Research Grant; Speed; Streptozocin; Structure; Topical agent; Topical application; Tretinoin; Ulcer; Work; Wound Healing; abstracting; base; collagenase; commercialization; diabetic; diabetic rat; disability; drug candidate; 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是一种合成类维甲酸，其刺激胶原合成和抑制皮肤中主要胶原降解酶的能力与全反式维甲酸（RA）相似。将MDI 301与RA区分开来的一个特点是，当局部应用于皮肤时，它没有刺激性。我们实验室过去的研究表明，局部预处理糖尿病类风湿性关节炎大鼠可改善随后引起的擦伤伤口的愈合。最近完成的这项SBIR资助的I期研究表明，MDI 301也能改善糖尿病大鼠擦伤伤口的愈合。第二阶段的研究就是以此为基础的。II期研究的工作计划包含三个具体目标：首先，使用与初始研究相同的大鼠链脲佐菌素诱导糖尿病模型，我们将确定MDI 301改善皮肤伤口愈合的程度。其次，利用从糖尿病患者身上获得的人体皮肤器官培养（来自危险部位和非危险部位的皮肤），我们将确定MDI 301对糖尿病患者皮肤生理变化的影响程度，这些变化有助于伤口成功愈合。最后，在目标三中，我们将继续进行FDA批准所需的MDI 301的安全性分析。

项目成果

Regulation of collagen turnover in human skin fibroblasts exposed to a gadolinium-based contrast agent.

• DOI: 10.1097/rli.0b013e3181a4d7e9
• 发表时间: 2009-08
• 期刊: Investigative radiology
• 影响因子: 6.7
• 作者: Bhagavathula N;DaSilva M;Aslam MN;Dame MK;Warner RL;Xu Y;Fisher GJ;Johnson KJ;Swartz R;Varani J
• 通讯作者: Varani J

Collagenolytic activity is suppressed in organ-cultured human skin exposed to a gadolinium-based MRI contrast agent.

• DOI: 10.1097/rli.0b013e3181bf95eb
• 发表时间: 2010-01
• 期刊: Investigative radiology
• 影响因子: 6.7
• 作者: Perone PA;Weber SL;DaSilva M;Paruchuri T;Bhagavathula N;Aslam MN;Dame MK;Johnson KJ;Swartz RD;Varani J
• 通讯作者: Varani J

Effects of gadolinium-based magnetic resonance imaging contrast agents on human skin in organ culture and human skin fibroblasts.

钆基磁共振成像造影剂对器官培养中的人体皮肤和人体皮肤成纤维细胞的影响。

• DOI: 10.1097/rli.0b013e31818f76b5
• 发表时间: 2009
• 期刊: Investigative radiology
• 影响因子: 6.7
• 作者: Varani,James;DaSilva,Marissa;Warner,RoscoeL;Deming,MonicaO'Brien;Barron,AdamG;Johnson,KentJ;Swartz,RichardD
• 通讯作者: Swartz,RichardD

Impaired keratinocyte function on matrix metalloproteinase-1 (MMP-1) damaged collagen.

• DOI: 10.1007/s00403-009-0948-4
• 发表时间: 2009-08
• 期刊: Archives of dermatological research
• 影响因子: 3
• 作者: Varani J;Perone P;Deming MO;Warner RL;Aslam MN;Bhagavathula N;Dame MK;Voorhees JJ
• 通讯作者: Voorhees JJ

Vascular tube formation on matrix metalloproteinase-1-damaged collagen.

• DOI: 10.1038/sj.bjc.6604357
• 发表时间: 2008-05-20
• 期刊: BRITISH JOURNAL OF CANCER
• 影响因子: 8.8
• 作者: Varani, J.;Perone, P.;Warner, R. L.;Dame, M. K.;Kang, S.;Fisher, G. J.;Voorhees, J. J.
• 通讯作者: Voorhees, J. J.