PROTEASE MODULATING WOUND DRESSINGS FOR THE TREATMENT OF VENOUS ULCERS

描述（由申请人提供）：据估计，美国有250万人患有慢性静脉溃疡。在发达国家，至少0.1%的成年人可能在某个时候经历静脉溃疡。静脉溃疡的总体患病率估计为每千人1.1至3.0例，随着年龄的增长，静脉溃疡的发病率呈指数增长，在80岁以上的人群中，静脉溃疡的发病率高达每千人20例。大约60-80%的慢性腿部溃疡有孤立的或主要的静脉成分，10-30%的病例伴有动脉功能不全。静脉溃疡发展缓慢，开始时常伴有肿胀。这些伤口通常发生在脚踝以上和膝盖以下，沿着小腿内侧的1/3（内踝），主要是由于静脉功能不全造成的。静脉功能不全的主要原因包括静脉曲张、深静脉血栓形成、肿瘤阻塞和先天性或获得性动静脉瘘，可能导致无法愈合的瘀血溃疡。复发风险较高的人群包括那些不能穿压缩袜的人，已知复发率高达所有病例的70%。此外，静脉溃疡疾病常并发蜂窝织炎，需要住院治疗或口服抗生素。现有的治疗方案，特别是压迫治疗、坏死组织清创、水肿治疗和感染控制，被认为可将复发率降低20-30%。尽管最近在伤口敷料和压迫绷带方面取得了进展，但静脉溃疡在临床上仍然很重要，而且难以治疗。因此，静脉溃疡的治疗需要很大一部分医疗资源。虽然目前静脉溃疡的护理标准为许多患者提供了好处，但仍有相当数量的溃疡无法愈合而成为慢性伤口。这种低成功率给社会带来了负担，每个静脉性腿部溃疡每月的医疗费用估计约为2400美元。据估计，在美国，每年治疗难以愈合的伤口的费用接近200亿美元。因此，人们一直在寻找额外的治疗化合物和/或设备，以提高标准护理之外的溃疡愈合。本提案公开了一种湿性伤口敷料，它具有将伤口中的水分从伤口中移走的能力，自然地从伤口中隔离中性粒细胞弹性酶，并且还添加了低剂量的金属蛋白酶抑制剂（抗生素），可以阻断一些已知阻碍愈合的有害伤口因子，特别是中性粒细胞胶原酶（MMP-8）。

DESCRIPTION (provided by applicant): It is estimated that 2.5 million people in the United States have chronic venous ulcers. In the developed world, at least 0.1% of the adult population is likely to experience venous ulceration at some time. With the overall prevalence, estimated to be between 1.1 and 3.0 incidents per one thousand individuals, occurrence of venous ulcers increases exponentially with age reaching as high as 20 cases per thousand in the population over 80 years of age. Approximately 60-80% of chronic leg ulcers have an isolated or predominant venous component and 10-30% of cases are associated with arterial insufficiency. Venous ulcers develop slowly and often initiate with swelling. These wounds typically occur above the ankle and below the knee, along the lower medial 1/3rd of the leg (medial malleolus) and result largely from venous insufficiency. The major causes of venous insufficiency, potentially leading to non-healing stasis ulcers, include varicose veins, deep venous thrombosis, neoplastic obstructions, and congenital or acquired arterio-venous fistulae. People at higher risk of recurrence include those unable to wear compression stockings and it is known that recurrence rates are as frequent as 70% of all cases. Furthermore, venous ulcer disease is often complicated by cellulitis necessitating hospitalization or oral antibiotics. Available and current treatment regimens, in particularly compression therapy, debridement of necrotic tissue, treatment of edema, and control of infection are believed to reduce recurrence rates from 20-30%. Despite recent advances in wound dressings and compression bandages, venous ulcers remain clinically significant and difficult to manage. As such, the treatment for venous ulceration claims a significant portion of healthcare resources. While the current standard of care for venous ulcers provides benefit to many patients, a significant number of ulcers fail to heal and become chronic wounds. This poor success rate burdens society with monthly healthcare costs estimated at approximately $2400 for each venous leg ulcer. It has been estimated that the annual treatment costs in the United States for hard to heal wounds is approaching as much as $20 billion. As such, there has been a search for additional therapeutic compounds and/or devices to enhance ulcer healing beyond that provided by standard care. This proposal discloses a moist wound dressing that has the capacity Jo move moisture away from the wound, naturally sequester neutrophil elastase from the wound, and also add a low-dose metalloproteinase inhibitor (antibiotic) that will block some amount of these noxious wound factors known to impede healing, specifically neutrophil collagenase (MMP-8).