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，至少有0.1%的成年人可能在某个时候经历静脉溃疡。总体患病率估计为每千人1.1至3.0例，静脉溃疡的发生率随年龄呈指数级增加，在80岁以上人群中高达每千人20例。大约60-80%的慢性腿部溃疡具有孤立的或主要的静脉成分，10-30%的病例与动脉功能不全有关。静脉性溃疡发展缓慢，通常以肿胀开始。这些伤口通常发生在踝关节上方和膝盖下方，沿着小腿内侧1/3（内踝），主要由静脉功能不全引起。静脉功能不全的主要原因可能导致不愈合的淤滞性溃疡，包括静脉曲张、深静脉血栓形成、肿瘤性阻塞和先天性或获得性动静脉瘘。复发风险较高的人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，静脉性溃疡疾病往往并发蜂窝织炎，需要住院治疗或口服抗生素。可用的和当前的治疗方案，特别是压迫疗法、坏死组织的清创术、水肿的治疗和感染的控制，被认为将复发率从20- 30%降低。尽管最近在伤口敷料和压迫绷带方面取得了进展，但静脉溃疡仍然具有临床意义，难以管理。因此，静脉性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益处，但大量溃疡未能愈合并成为慢性伤口。这种低成功率给社会带来负担，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，美国每年用于难以愈合的伤口的治疗费用接近200亿美元。因此，一直在寻找额外的治疗化合物和/或装置，以增强标准护理所提供的溃疡愈合。 该提案公开了一种湿润的伤口敷料，其具有将水分从伤口移走、从伤口自然隔离嗜中性粒细胞弹性蛋白酶的能力，并且还添加了低剂量的金属蛋白酶抑制剂（抗生素），其将阻断一定量的已知阻碍愈合的这些有害伤口因子，特别是嗜中性粒细胞胶原酶（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).