Production of a dissolvable hydrogel-based wound dressing for second degree burns

抽象的。本提案描述了一种新型水凝胶型烧伤敷料的开发 可吸收渗出物的创面敷料，可保护伤口免受细菌感染，并可轻松去除 从二度烧伤的表面通过溶解，从而避免了对伤口的创伤和对患者的痛苦。 烧伤是最常见和最具破坏性的创伤之一。数百万患者遭受与烧伤有关的痛苦 虽然严重烧伤的频率较低，但这些患者可能会残疾、毁容 以及在治疗过程中甚至治疗后的心理损害。据报道，更换烧伤敷料是 最痛苦的时间(首次烧伤后)和阿片类药物是烧伤患者减轻疼痛的主要手段。这个 需要ICU/或级别护理的典型损伤的烧伤敷料更换持续时间通常为60分钟以上 全身麻醉诱导时间可延长至三个小时以上。目前，可商业化的 敷料会粘在伤口表面，因此敷料的更换会导致新形成的组织受到创伤， 延迟愈合，在二度烧伤中，神经末梢仍然完好无损，给患者带来极大的痛苦。 我们对这个问题的解决方案是Hydraid Burn敷料。九头蛇酱由一种胺组成- 端基树枝状分子和含有内部硫酸酯的双功能NHS活化的聚乙二醇酯 其他形成硫酯连接的水凝胶敷料，该敷料随后可通过暴露于水中而溶解 硫醇溶液通过硫醇-硫酯交换机制。我们成功的第一阶段工作表明：1)我们的能力 合成水合物成分；2)渗出物模拟物的吸收和溶胀；3)缺乏体外 细胞毒性或巨噬细胞激活；4)二度烧伤后按需通过体内溶解去除 半胱氨酸甲酯溶液的应用；5)预防体内二度烧伤的细菌感染； 6)与传统绷带相比，愈合的优势具有可比性和趋势性；以及，7)易于“喷雾”。 开/喷“用于覆盖人类手部复杂的表面、手指和网状物。的最终目标是 拟议的项目是获得Hydraid Burn敷料的510(K)许可。与这一目标相一致的是 完成四个主要产品开发类别中的关键通过/不通过里程碑：1)制造，2) 工作台和动物测试，3)人为因素(非临床)可用性测试，以及4)管理事务。目标1： 将生产方法转让给合同制造合作伙伴(PCI合成)并执行初始装瓶 生产运行(Power Container Corp.)提供成品用于目标2和目标3的评估。目标2：确认 湿润烧伤敷料在大面积烧伤创面中的优势及应用 国际标准化组织10993安全和生物兼容性测试。目标3：进行人为因素和非临床可用性测试 并开发标签，包括使用说明。目标4：执行监管战略，包括：标签和 可用性测试战略，与FDA的提交前会议，以及向FDA提交510(K)。成功 这些目标的实现将使离子制药公司开始生产、营销和销售Hydraid。

ABSTRACT. This proposal describes the development of the HydrAid Burn Dressing—a novel hydrogel-based wound dressing that absorbs exudate, protects the wound from bacterial infection and can be easily removed from the surface of 2nd degree burns via dissolution thereby averting trauma to the wound and pain to the patient. Burns are one of the most common and devastating forms of trauma. Millions of patients suffer burn-related injuries each year and, while severe burns are less frequent, these patients may suffer disability, disfigurement and psychological damage during and even after treatment. Changing of burn dressings is reported to be the most painful time (after the initial burn) and opioids are the mainstay of pain mitigation for burn patients. The duration of a burn dressing change in a typical injury requiring ICU/OR-level care is often 60+ minutes with induction of general anesthesia and can extend to more than three hours. At present, commercially available dressings adhere to the wound surface so that dressing changes lead to traumatization of newly formed tissues, delayed healing and, in 2nd degree burns where nerve endings are still intact, excruciating pain for the patient. Our solution to this problem is the HydrAid Burn Dressing. The HydrAid dressing is composed of an amine- terminated dendron and a bifunctional NHS-activated PEG containing an internal thioester that react with each other to form a thioester-linked hydrogel dressing that can be subsequently dissolved by exposure to an aqueous thiol solution via a thiol-thioester exchange mechanism. Our successful Phase I work demonstrates: 1) our ability to synthesize the HydrAid components; 2) absorption and swellability with exudate mimics; 3) lack of in vitro cytotoxicity or macrophage activation; 4) on-demand removal by dissolution in vivo on a 2nd degree burn by application of a cysteine methyl ester solution; 5) prevention of bacterial infections in 2nd degree burns in vivo; 6) comparable and trending superiority of healing compared to traditional bandages; and, 7) easy “spray- on/spray-off” use in covering the intricate surfaces, digits, and webbing of a human hand. The ultimate goal of the proposed project is to obtain 510(k) clearance for the HydrAid Burn Dressing. Aligned with this goal is the completion of key Go/No-Go milestones in four primary product development categories: 1) Manufacturing, 2) Bench and animal testing, 3) Human Factors (non-clinical) usability testing, and 4) Regulatory affairs. Aim 1: Transfer production methods to Contract Manufacturing partners (PCI Synthesis) and perform an initial bottling production run (Power Container Corp.) to provide finished product for evaluation in Aims 2 and 3. Aim 2: Confirm HydrAid Burn Dressing superiority to conventional dressings in large surface area burns and perform relevant ISO 10993 safety and biocompatibility testing. Aim 3: Conduct Human Factors and non-clinical usability testing and develop labeling, including Instructions for Use. Aim 4: Execute regulatory strategy, including: labeling and usability testing strategy, pre-submission meeting with the FDA, and 510(k) submission to the FDA. Successful completion of these aims will position Ionic Pharma to begin production, marketing and sales of HydrAid.