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: 7106996
• 负责人: William Paul Purcell
• 金额: $ 10万
• 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 2007-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7106996
• 关键词: analog; collagen; collagenase; diabetes mellitus; irritation /irritant; laboratory rat; nonhuman therapy evaluation; protein biosynthesis; retinoate; skin disorder chemotherapy; skin pharmacology; skin ulcer; streptozotocin; therapy design /development; topical drug application; wound healing

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 major feature that distinguishes MDI 301 from RA is its lack of irritation when applied topically to skin. Recent studies from our laboratory have shown that topical treatment of diabetic rats with RA improves the healing of subsequently-induced abrasion wounds. Based on this, we have proposed the prophylactic use of RA as a way to improve structure/function in diabetic skin at risk for ulcer formation. A potential drawback to this strategy is skin irritation. If retinoid use in diabetic skin provokes irritation, this could result in non-use (as is does in other groups of retinoid users). Additionally, if the degree of irritation is too great, the irritation could counter-act the beneficial effects of retinoid treatment in the at-risk skin. 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 without the negative consequence seen with RA use, it will provide a better agent for development as a chronic wound preventative. To achieve our overall goal, we will compare the effects of topical MDI 301 treatment with topical RA on dermal structure/function in streptozotocin diabetic (STZ-D) rats and compare healing of abrasion wounds in control rats, STZ-D rats and STZ-D rats that have been pretreated with topical RA or topical MDI 301.

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。MDI 301区别于RA的主要特征是其在局部应用于皮肤时缺乏刺激性。我们实验室最近的研究表明，用RA局部治疗糖尿病大鼠可改善非自愿性磨损伤口的愈合。基于此，我们提出了预防性使用RA作为一种改善糖尿病皮肤溃疡形成风险的结构/功能的方法。这种策略的潜在缺点是皮肤刺激。如果类维生素A在糖尿病皮肤中的使用引起刺激，这可能导致不使用（就像其他类维生素A使用者群体一样）。此外，如果刺激程度太大，则刺激可能会抵消类维生素A治疗在危险皮肤中的有益效果。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，而没有使用RA所看到的负面后果，则它将提供更好的药物用于开发作为慢性伤口预防剂。为了实现我们的总体目标，我们将比较局部MDI 301治疗与局部RA对链脲佐菌素糖尿病（STZ-D）大鼠的皮肤结构/功能的影响，并比较对照大鼠、STZ-D大鼠和已经用局部RA或局部MDI 301预处理的STZ-D大鼠中擦伤伤口的愈合。