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

用于二度烧伤的可溶性水凝胶伤口敷料的生产

• 批准号: 10324951
• 负责人: Aaron Henry Colby
• 金额: $ 83.03万
• 依托单位: IONIC PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10324951
• 关键词: Acute Pain; Aerosols; Aftercare; Amines; Anesthesia procedures; Animal Testing; Animals; Area; Bacterial Infections; Bandage; Biocompatible Materials; Body Surface Area; Burn Trauma; Burn injury; Caliber; Caring; Categories; Cessation of life; Characteristics; Chemicals; Cicatrix; Clinical; Complex; Consumption; Contracts; Cysteine; Cytoplasmic Granules; Data; Debridement; Dendrimers; Dermis; Development; Digit structure; Economics; Elasticity; Ensure; Environment; Epithelial; Etiology; Evaluation; Excision; Exposure to; Exudate; Family suidae; Fibrinogen; Fire - disasters; Freezing; Gel; General Anesthesia; Goals; Grant; Hand; Hour; Human; Human Resources; Hydrogel Bandage; Hydrogels; Impaired healing; In Situ; In Vitro; Infection; Injury; Instruction; Internet; Ions; Joints; Label; Language; Lead; Link; Liquid substance; Macrophage Activation; Marketing; Measures; Mechanics; Methods; Modeling; Movement; Nerve Endings; Nerve Pain; Operative Surgical Procedures; Opioid; Pain; Pain management; Pain-Free; Painless; Patients; Performance; Phase; Positioning Attribute; Prevention; Procedures; Process; Production; Regulatory Affairs; Reporting; Resistance; Running; Safety; Sales; Secure; Silver; Site; Small Business Innovation Research Grant; Spray-On Dressings; Sterile coverings; Sulfhydryl Compounds; Surface; System; Technology; Testing; Time; Tissues; Trauma; Trauma patient; Work; Wound models; absorption; aqueous; base; biomaterial compatibility; burn wound; cost; cytotoxicity; design; disability; epithelial wound; flexibility; healing; improved; in vivo; mecysteine; meetings; microbial; novel; pain patient; pain receptor; pain reduction; product development; prototype; psychologic; safety study; scale up; second degree burn; severe burns; success; thioester; trend; usability; wound; wound closure; wound dressing; wound healing

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.

抽象的。该提案描述了水力燃烧敷料的发展 - 一种新型水凝胶 吸收成人，保护伤口免受细菌感染的伤口敷料，可以轻松去除 从第二度的表面通过溶解燃烧，从而使伤口避免创伤，并使患者疼痛。 烧伤是最常见和毁灭性的创伤形式之一。数百万患者遭受烧伤相关 每年受伤，尽管严重烧伤的频率较小，但这些患者可能会遭受残疾，毁容 以及在治疗期间甚至在治疗后的心理损害。据报道，更换烧焦的敷料是 最痛苦的时间（最初燃烧后）和阿片类药物是缓解疼痛患者的支柱。这 需要ICU/OR-level护理的典型伤害中燃烧敷料的持续时间通常为60分钟以上 诱导全身麻醉，可以延伸至三个以上。目前，可商购 敷料粘附在伤口表面，以使敷料变化会导致新形成的组织的创伤， 延迟愈合，在神经末梢仍然完好无损的二级燃烧中，患者疼痛令人痛苦。 我们解决这个问题的解决方案是Hydraid Burn敷料。氢料敷料由胺组成 终止的树突和双功能NHS激活的PEG，其中包含一个与每个反应的内部壳 其他可以形成与硫酯连接的水凝胶敷料，随后可以通过暴露于水中溶解 硫醇溶液通过硫醇 - 硫酯交换机制。我们成功的阶段我的工作证明：1）我们的能力 合成水力组件； 2）具有渗出模仿的遭受痛苦和膨胀性； 3）缺乏体外 细胞毒性或巨噬细胞激活； 4）通过在体内溶解在2度燃烧中通过体内溶解的按需去除 半胱氨酸甲酯溶液的应用； 5）预防体内2度烧伤中的细菌感染； 6）与传统绷带相比，治愈的优势可比性和趋势优势； 7）轻松“喷涂 - 在覆盖人手的复杂表面，数字和织带中的使用。 拟议的项目是获得510（k）的氢烧伤敷料。与这个目标保持一致的是 在四个主要产品开发类别中完成关键GO/NO-GO里程碑：1）制造，2） 长凳和动物测试，3）人为因素（非临床）可用性测试，以及4）监管事务。目标1： 将生产方法转移给合同制造合作伙伴（PCI合成）并进行初始装瓶 生产运行（Power Container Corp.）在目标2和3中提供用于评估的成品。目标2：确认 在大型表面积燃烧中，水力燃烧的敷料优越性比传统敷料燃烧并执行相关 ISO 10993安全性和生物相容性测试。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：执行监管策略，包括：标签和 可用性测试策略，与FDA的提交前会议以及向FDA提交的510（k）。成功的 这些目标的完成将使离子制药公司开始生产，营销和Hydraid的销售。