Treatment of Wound Infection with Novel Uncharged Silver Carbene Complexes

用新型不带电银卡宾配合物治疗伤口感染

基本信息

批准号：
8453014
负责人：
DAVID J VACHON
金额：
$ 30万
依托单位：
IASIS MOLECULAR SCIENCES, INC
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-20 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8453014
关键词：
Accounting Address Affect American Amputation Animal Model Animals Antibiotics Back Bacteria Biological Burn injury Characteristics Chemicals Chronic Complex Dermal Development Diabetes Mellitus Diabetic Foot Ulcer Dose Drug Delivery Systems Drug Formulations Effectiveness Erythema Evaluation Fibroblasts Foot Ulcer Gel Goals Healed Histocompatibility Hospitalization Hydrogels Imagery Impaired wound healing In Vitro Infection Inflammation Inflammatory Response Invaded Liquid substance Maintenance Maximum Tolerated Dose Measurement Measures Medical Methicillin Resistance Microbial Biofilms Modeling Nature Ointments Osteomyelitis Outcome Oxidative Stress Patients Perfusion Peroxidases Petrolatum Phase Preparation Process Pseudomonas aeruginosa Rattus Research Resistance Resolution Silver Site Solubility Staging Staphylococcus aureus Sterile coverings Streptozocin Sulfadiazine Symptoms Technology Testing Therapeutic Therapeutic Agents Thick Tissues Topical Antibiotic Toxic effect Treatment outcome Water Work Wound Infection antimicrobial antimicrobial drug base biomaterial compatibility carbene combat cost cytotoxicity design diabetic diabetic rat effective therapy healing improved in vivo indexing innovation microbial microbicide novel pathogen patient population programs resistant strain wound

项目摘要

DESCRIPTION (provided by applicant): Three novel uncharged silver carbene microbicides that have been shown to be effective against a wide variety of pathogens will be formulated into two different ointment formulations and tested in an infected healing model in the diabetic rat. Formulation of the silver carbenes into one of either a transparent (gel) wound ointment that will allow viewing of the wound while being treated or an occlusive petrolatum-based ointment that is anticipated to have different moisture retention and drug delivery characteristics that a water-based gel will be carried out. The major specific aims of the proposed research involve the preparation & formulation/processing of the silver carbene antimicrobial agents into an ointment form, chemical and biological characterization, determination of maximum tolerated doses, and evaluation in an infected wound model in the rat. The biological characterization involves the determination of the MIC90 for each compound and evaluation of the toxicity of each compound formulated into an ointment over a two log range starting at a concentration (in the ointment) at the MIC90. The primary objectives of the proposed therapy are: 1) resolution of infection, 2) minimization of inflammation, and 3) encouragement of wound resolution. This innovative and rational approach to a topical antimicrobial therapy is founded on the basis of several different studies that have revealed promising bio-applicable attributes of these silver carbene complexes. The end-goal of this project is to enable the next phase of development of one or more of these novel microbicidal compounds that will be targeted for the treatment of infected chronic wounds and burns while developing a greater understanding of the mechanisms by which these compounds work. PUBLIC HEALTH RELEVANCE: Diabetic foot ulcers are a common type of chronic wound affecting as many as 25% of all diabetics and in many cases diabetics develop infection as a consequence of an impaired inflammatory response. Infection can greatly complicate treatment and outcomes for diabetic foot ulcers with 65% of all patients developing osteomyelitis and amputation in 14-24% of the osteomyelitis group (American Diabetes Association, 1999). Complications associated with foot ulcers account for 20-25% of all hospitalizations costing billions of dollars annually and despite the important medical advances that have been made in the treatment of diabetic foot ulcers in the past fifty years, there remains a significant need for more effective therapies to combat infection and impaired wound healing in this patient population.

描述（由申请人提供）：三种新型未加成的非充电银碳纤维微生物已被证明对多种病原体有效，将被配合为两种不同的软膏制剂，并在糖尿病大鼠的感染愈合模型中进行了测试。将银碳纤维构成透明（凝胶）伤口软膏之一，该软膏将允许在接受治疗时观察伤口，或者是闭塞性石油的软膏，预计将具有不同的水分保留和药物递送特性，该特征将进行水性凝胶。提出的研究的主要特定目的涉及将银卡宾抗微生物剂制备/加工/加工/加工/加工/处理药膏形式，化学和生物学特征，确定最大耐受剂量的最大剂量以及在大鼠感染伤口中的评估。生物学表征涉及每种化合物的MIC90的测定，并评估每种化合物的毒性，该化合物在MIC90处的浓度（药膏）浓度（在药膏中）开始在两个log范围内配制成软膏。拟议治疗的主要目标是：1）感染的分辨率，2）最小化炎症和3）鼓励伤口分辨率。这种对局部抗微生物治疗的创新和合理的方法是基于几项不同的研究，这些研究揭示了这些银碳酸银络合物的有希望的生物适用属性。该项目的最终目标是使这些新型杀生化合物中的一个或多个开发的下一阶段，该化合物将用于治疗感染的慢性伤口和燃烧，同时对这些化合物起作用的机制有更深入的了解。公共卫生相关性：糖尿病足性溃疡是一种常见的慢性伤口类型，影响了所有糖尿病患者的25％，并且在许多情况下，糖尿病患者由于炎症反应受损而形成感染。感染可能会使糖尿病足溃疡的治疗和结果复杂化，其中65％的患者患骨髓炎和截肢术的14-24％（美国糖尿病协会，1999年）。与足球溃疡相关的并发症占所有住院的20-25％，尽管在过去五十年中，在治疗糖尿病足溃疡方面取得了重要的医疗进展，但仍有很大的需求在该患者人群中，更有效的疗法可抵抗感染和伤口愈合受损。