Topical Skin Treatment to Facilitate Wound Healing in the Aged Population

局部皮肤治疗促进老年人伤口愈合

• 批准号: 7478462
• 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: 2008
• 资助国家: 美国
• 起止时间: 2008-07-25 至 2009-01-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478462
• 关键词: Adrenal Cortex Hormones; Animals; Applications Grants; Atrophic; Chronic; Collagen; Control Animal; Development; Goals; Healed; MDI 301; Matrix Metalloproteinases; Medical; Phase; Population; Production; Public Health; Rattus; Retinoids; Skin; Skin Aging; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Structure; Topical application; Tretinoin; Week; Work; Wound Healing; aged; collagenase; healing; improved; irritation; repaired; skin irritation; treatment duration; wound

DESCRIPTION (provided by applicant): MDI-301 is a synthetic retinoid. MDI-301, like RA, induces collagen synthesis and reduces expression of collagen-degrading matrix metalloproteinases in the skin. This agent also induces epidermal thickening. However, unlike RA, MDI-301 is non-irritating when applied topically. In a recent study we showed that MDI-301 was effective in promoting the healing of superficial abrasion wounds in hairless rats with skin made atrophic by corticosteroid treatment. Given these findings, we propose in this Phase I SBIR grant application to topically treat aged hairless rats with MDI-301 for a two-week period. Control animals will be treated with vehicle alone or with RA as a positive control. During the treatment period, animals will be examined for skin irritation. Following treatment, skin will be obtained and analyzed for collagen production and for elaboration of collagen-degrading enzymes. In other animals, superficial abrasion wounds will be induced following treatment. Healing in control and MDI-301-treated animals will be compared. If we can demonstrate that MDI-301 promotes healing of superficial abrasion wounds in aged skin but does not induce significant irritation, this will provide a strong impetus for development of this agent as a non-irritating "wound preventative". The medical benefit and commercial potential will be significant. PUBLIC HEALTH RELEVANCEThe goal of this work is to develop a non-irritating retinoid for topical use in aged skin. The non-irritating retinoid will, hopefully, improve the structure and function of aged skin so that it will resist formation on non-healing wounds. It should do so without irritation.

描述（由申请人提供）：MDI-301是一种合成类维生素A。 MDI-301 与 RA 一样，诱导胶原蛋白合成并减少皮肤中胶原蛋白降解基质金属蛋白酶的表达。该剂还可引起表皮增厚。然而，与 RA 不同，MDI-301 局部使用时无刺激性。在最近的一项研究中，我们表明 MDI-301 可有效促进因皮质类固醇治疗而导致皮肤萎缩的无毛大鼠浅表擦伤伤口的愈合。鉴于这些发现，我们建议在此 I 期 SBIR 拨款申请中使用 MDI-301 局部治疗老年无毛大鼠两周。对照动物将单独用载体或用RA作为阳性对照进行治疗。在治疗期间，将检查动物的皮肤刺激情况。治疗后，将获取皮肤并分析胶原蛋白的产生和胶原蛋白降解酶的阐述。在其他动物中，治疗后会引起浅表擦伤。将比较对照动物和 MDI-301 治疗动物的愈合情况。如果我们能够证明MDI-301能够促进老化皮肤浅表擦伤的愈合，但不会引起明显的刺激，这将为开发该药物作为无刺激性“伤口预防剂”提供强大的动力。医疗效益和商业潜力将是巨大的。公共健康相关性这项工作的目标是开发一种无刺激性的类维生素A，用于老化皮肤的局部使用。无刺激性的类视黄醇有望改善老化皮肤的结构和功能，从而抵抗不愈合伤口的形成。它应该在没有刺激的情况下这样做。