Topical Therapeutic to Promote Healing of Chronic Wounds

描述（由申请人提供）：四肢的慢性难治性或不愈合性伤口或溃疡是影响数百万患者的主要医疗状况。慢性伤口的定义是伤口在使用局部/手术治疗措施6个月后没有显示出明显愈合或进展的迹象。无法愈合的伤口影响了650万患者，影响了近2%的美国人口，医疗保健系统每年的成本为250亿美元。随着人口老龄化和糖尿病发病率的增加，这些数字正在上升，糖尿病是难治性腿部溃疡的主要原因。其他引起慢性伤口的常见原因包括静脉淤积性溃疡和卧床性溃疡，这些溃疡发生在不能活动的病人身上。目前对四肢（糖尿病、静脉淤积）或卧疮的治疗通常不能产生持续或完全的愈合。在糖尿病患者中，超过一半的溃疡在三年内复发，15%的溃疡最终需要截肢，导致严重的残疾。对于这一巨大的健康负担，需要新的治疗药物来促进伤口的完全愈合。主要研究人员已经确定了一种药物（精氨酸丁酸盐，AB），当肠外给药时，显着加速愈合，包括高度难治性慢性伤口人群的完全愈合，镰状细胞腿溃疡，

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.