Protease Indicator for Chronic Wound Management

慢性伤口管理的蛋白酶指标

• 批准号: 7108124
• 负责人: IRWIN KELMAN COHEN
• 金额: $ 11.86万
• 依托单位: BIO-SENSE, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7108124
• 关键词: bioassay; biosensor device; collagenase; colorimetry; elastases; extended care; fluorimetry; high throughput technology; human tissue; immunoaffinity chromatography; method development; noninvasive diagnosis; patient care management; patient oriented research; reagent /indicator; wound healing

DESCRIPTION (provided by applicant): Chronic wounds are characterized by an overabundant presence of polymorphonuclear leukocytes(PMN's) which produce excessive elastase and the PMN collagenase , MMP-8. Collagenase destroys the wound matrix while elastase degrades growth factors and their receptor sites. These excessive proteases can be lowered by radical surgical debridement of the wound to promote healing. Once the wound proteases are lowered, host growth factors will be functional and/or the clinician can add extrinsic growth factors to the wound without degradation by these deleterious enzymes. More recently, protease sequestering dressings have been developed to lower protease content for improved healing. However, determination that the protease level has been lowered requires laboratory study of wound fluids or biopsies with at least a 24 hour delay before the information is returned to the clinician. Using the methodology to be developed in this proposal, a rapid, safe, inexpensive bed-side measurement of collagenase and elastase can be made which will determine when the protease sequestering dressing can be stopped safely. At present, the decision to change to another form of dressing is made imperically by simply observing the appearance of the wound. 2 approaches will be evaluated. The first approach will be to assay both proteases using rapid immunochromatographic methods. The second approach will be to assay elastase by a rapid colorimetric or fluorometric method. The methods will be validated using purified proteins, artificial wound fluids, and patient wound fluid samples. The assays used to develop this product are standard and should lead to a commercial product development in a Phase II study. Commercial production of the device and FDA approval as such should be straight forward. Cost of production will be low and therefore, broad usage and company profit is expected. The benefits to our patient population with chronic wounds should be significant.

描述（由申请人提供）：慢性伤口的特征是存在过多的多形核白细胞（PMN's），其产生过量的弹性蛋白酶和PMN胶原酶MMP-8。胶原酶破坏伤口基质，而弹性蛋白酶降解生长因子及其受体位点。通过对伤口进行彻底的清创手术可以降低这些过量的蛋白酶，以促进愈合。一旦伤口蛋白酶降低，宿主生长因子将发挥作用和/或临床医生可以向伤口添加外源生长因子，而不会被这些有害酶降解。最近，已开发出蛋白酶隔离敷料来降低蛋白酶含量以改善愈合。然而，要确定蛋白酶水平已降低，需要对伤口液体或活检进行实验室研究，并在信息返回给临床医生之前至少延迟 24 小时。使用本提案中开发的方法，可以对胶原酶和弹性蛋白酶进行快速、安全、廉价的床边测量，这将确定何时可以安全地停止蛋白酶隔离敷料。目前，仅通过观察伤口的外观就可以做出更换另一种敷料的决定。将评估 2 种方法。第一种方法是使用快速免疫层析方法测定这两种蛋白酶。第二种方法是通过快速比色法或荧光法测定弹性蛋白酶。这些方法将使用纯化的蛋白质、人造伤口液和患者伤口液样本进行验证。用于开发该产品的测定是标准的，应该会导致 II 期研究中的商业产品开发。该设备的商业化生产和 FDA 的批准应该是直接的。生产成本较低，因此预计用途广泛，公司利润可期。对于患有慢性伤口的患者群体来说，其益处应该是显着的。