A Novel & Tailorable Topical Wound Therapy Based on a Semi-Interpenetrating Polym

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• 批准号: 7275122
• 负责人: DAVID J VACHON
• 金额: $ 14.13万
• 依托单位: IASIS MOLECULAR SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275122
• 关键词: Novel; Tailorable; Topical; Wound; Therapy

DESCRIPTION (provided by applicant): Abstract A water-soluble, inexpensive, and biocompatible polymer with unique properties and processing characteristics has been proven effective against multiple serine and metalloproteases in testing. The polymer is used to formulate wound therapies that offer an alternative to existing costly products. The major specific aim(s) of this work detail the formulation and animal evaluation of a hydrogel dressing that releases the water-soluble polymer agent in order to control the proteolytic environment of a chronic wound as well as deliver a secondary agent such as an anti-oxidant. This simple and rational therapy is based upon the idea that controlling proteolysis in a chronic wound environment could result in a more favorable healing environment. The polymer technology described herein may have application beyond wound therapies where controlling proteases and delivering a secondary agent simultaneously may be beneficial. Conservative estimates suggest that over 2 million people annually in the U.S. suffer from chronic ulcers (Rees et. al., 1999) and these numbers are expected to increase in view of the aging population and the rise of diabetes. The prevalence of diabetes for all age-groups worldwide has been estimated to be 2.8% in 2000 and will rise to 4.4% in 2030. Accordingly, the total number of people with diabetes is projected to approach 366 million in 2030. Among persons diagnosed as having diabetes mellitus, the prevalence of foot ulcers is 4% to 10%, the annual population-based incidence is 1.0% to 4.1%, and the lifetime incidence may be as high as 25%. In addition, the incidence of ulcer recurrence after complete healing approaches 30% within 12 months. Diabetic foot ulcers cause substantial emotional, physical, productivity, and financial losses. The estimated cost of treating a diabetic foot ulcer in 1999 was $18,000. In instances requiring amputation, these costs jumped to $28 000. These estimates do not take into account the personal and socioeconomic impact of these wounds on a patient's life. A wound treatment that utilizes a commercially available & inexpensive, water- soluble polymer of tailorable utility that leverages our fundamental understanding of the underlying biology and biochemistry of chronic wounds in order to provide a multifaceted treatment is the subject of our investigation. The water-soluble polymer will be formulated into a dressing of three derivative forms that will be evaluated for their capacities to control the levels of certain damaging wound proteases via inhibition, and affect the wound by additionally delivering an NO donor, an NO precursor, or an antioxidant to the wound site.

描述（由申请人提供）：摘要一种具有独特性质和加工特性的水溶性、廉价和生物相容性聚合物已在测试中被证明对多种丝氨酸和金属蛋白酶有效。该聚合物用于配制伤口疗法，为现有昂贵的产品提供替代品。这项工作的主要具体目标详细说明了水凝胶敷料的配方和动物评价，该敷料释放水溶性聚合物试剂，以控制慢性伤口的蛋白水解环境，并递送第二试剂，如抗氧化剂。这种简单而合理的疗法是基于这样的想法，即在慢性伤口环境中控制蛋白水解可以产生更有利的愈合环境。本文所述的聚合物技术可以具有超出伤口治疗的应用，其中控制蛋白酶和同时递送第二药剂可能是有益的。保守估计表明，美国每年有超过200万人患有慢性溃疡（Rees et.例如，1999年），而且鉴于人口老龄化和糖尿病的增加，这些数字预计还会增加。据估计，2000年全球所有年龄组的糖尿病患病率为2.8%，2030年将上升至4.4%。因此，预计2030年糖尿病患者总数将接近3.66亿。在诊断为糖尿病的人群中，足部溃疡的患病率为4%至10%，基于人群的年发病率为1.0%至4.1%，终生发病率可能高达25%。此外，溃疡完全愈合后12个月内复发率接近30%。糖尿病足溃疡会导致大量的情感、身体、生产力和经济损失。1999年治疗糖尿病足溃疡的估计费用为18 000美元。在需要截肢的情况下，这些费用跃升至28 000美元。这些估计没有考虑到这些伤口对患者生活的个人和社会经济影响。我们研究的主题是一种伤口治疗，其利用市售且廉价的、可定制用途的水溶性聚合物，利用我们对慢性伤口的基础生物学和生物化学的基本理解，以提供多方面的治疗。将水溶性聚合物配制成三种衍生物形式的敷料，将评估它们通过抑制来控制某些损伤性伤口蛋白酶的水平的能力，并通过另外将NO供体、NO前体或抗氧化剂递送至伤口部位来影响伤口。