Topical Therapeutic to Promote Healing of Chronic Wounds

描述（由申请人提供）：慢性难治性或不愈合的四肢伤口或溃疡是影响数百万患者的主要医疗状况。慢性伤口定义为在使用局部/手术治疗措施6个月后未显示出显著愈合或进展迹象的伤口。不愈合的伤口影响了650万患者，影响了近2%的美国人口，每年给医疗保健系统造成的成本为250亿美元。这些数字随着人口老龄化和糖尿病发病率的增加而上升，糖尿病是难治性腿部溃疡的主要原因。慢性伤口的其他常见原因包括静脉淤滞性溃疡和在固定患者中发展的褥疮性溃疡。目前对肢体（糖尿病、静脉淤滞）或褥疮溃疡的治疗通常不能产生持续或完全愈合。在糖尿病患者中，超过一半的溃疡在三年内复发，15%最终需要截肢，并导致严重的残疾。对于这种巨大的健康负担，需要促进伤口完全闭合的新治疗剂。 主要研究者已经确定了一种药物（精氨酸丁酸盐，AB），当胃肠外给药时，可显著加速愈合，包括高度难治性慢性伤口人群的完全愈合，镰状细胞腿部溃疡， [其愈合速度比类似的褥疮或糖尿病溃疡慢10-20倍]。胃肠外给药的药物具有良好的安全性。尽管通过留置输液港装置进行的胃肠外（IV）给药对于既往临床试验中研究的极重度人群是可接受的，但局部给药系统将为更广泛的应用提供许多可行性优势，并且不需要主要在临床机构中给药。Phoenicia Biosciences开发了一种相同药物的创新原型局部喷雾输送系统。这种一流的治疗方法应该对慢性伤口日益增长的医疗保健问题所带来的痛苦和经济负担产生非常重要的影响。 该I期申请的目的是：（I）开发AB的新的局部树枝状聚合物水凝胶喷雾制剂，并在两种伤口愈合的动物模型（慢性伤口愈合模型和糖尿病慢性伤口愈合模型）中测试新的局部制剂的活性;（II.）进行精氨酸丁酸盐新型外用制剂的新IND所需的CMC研究。这些IND使能研究将允许这种新的治疗方法在临床试验中进行测试。

DESCRIPTION (provided by applicant): Chronic refractory, or non-healing, wounds or ulcerations of the extremities represent a major medical condition affecting millions of patients. A chronic wound is defined as a wound that does not show signs of significant healing, or progresses, after use of topical/surgical treatment measures for six months. Non-healing wounds affect 6.5 million patients, affecting nearly 2% of the U.S. population, with an annual cost to the healthcare system of $25 billion. These numbers are rising with the aging population and the increasing incidence of diabetes, a leading cause of refractory leg ulcers. Other common causes of chronic wounds include venous stasis ulcers, and decubitus ulcers which develop in immobilized patients. Current treatments for extremity (diabetic, venous stasis) or decubitus ulcers often do not produce sustained or complete healing. Among diabetics, over half of ulcers recur within three years, and 15% ultimately require amputations, with significant consequent disability. New therapeutic agents that promote complete wound closure are needed for this enormous health burden. The Principal Investigators have identified a drug (Arginine Butyrate, AB) which, when given parenterally, dramatically accelerates healing, including complete healing in a highly-refractory chronic wound population, sickle cell leg ulcers, [which heal 10-20 times more slowly than comparable decubitus or diabetic ulcers]. The parenterally-delivered drug had a benign safety profile. Although parenteral (IV) delivery via indwelling port devices was acceptable for the extremely severe population studied in the prior clinical trial, a topical delivery system would offer many feasibility advantages for broader application and not require delivery primarily in clinical facilities. Phoenicia Biosciences has developed an innovative prototype topical spray delivery system of the same drug. This first-in-class therapeutic should provide a highly significant impact on the suffering and economic burden imposed by the growing health care problem of chronic wounds. The Aims of this Phase I application are: (I) Develop a new topical dendrimer hydrogel spray preparation of AB, and test the activity of the new topical preparation in two animal models of wound healing (a chronic wound healing model and diabetic chronic wound healing model); (II.) Perform CMC studies required for a new IND of the novel topical formulation of Arginine Butyrate. These IND enabling studies will allow this new therapeutic to be tested in clinical trials.