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.

摘要。该提案描述了HydrAid烧伤敷料的开发-一种新型水凝胶基 吸收渗出物的伤口敷料，保护伤口免受细菌感染，并且可以容易地去除 从二度烧伤的表面通过溶解，从而避免创伤的伤口和疼痛的病人。 烧伤是最常见和最具破坏性的创伤形式之一。数以百万计的病人遭受烧伤有关的 虽然严重烧伤的发生率较低，但这些患者可能会遭受残疾，毁容， 以及治疗期间甚至治疗后的心理伤害。据报道，更换烧伤敷料是 最痛苦的时间（最初烧伤后）和阿片类药物是减轻烧伤患者疼痛的主要手段。的 在需要ICU/OR级护理的典型损伤中，烧伤敷料更换的持续时间通常为60分钟以上， 全身麻醉的诱导时间可延长至3小时以上。目前，市场上有 敷料粘附在伤口表面上使得敷料的更换导致新形成的组织的创伤， 延迟愈合，并且在神经末梢仍然完整的二度烧伤中，对患者来说是难以忍受的疼痛。 我们解决这个问题的方法是HydrAid烧伤敷料。HydrAid敷料由胺组成- 封端的树枝化基元和含有内部硫酯的双官能NHS活化的PEG，所述内部硫酯与每个 另一种是形成硫酯连接的水凝胶敷料， 通过硫醇-硫酯交换机制，在硫醇溶液中进行。我们成功的第一阶段工作表明：1）我们的能力 合成HydrAid成分; 2）与渗出液模拟物的吸收和溶胀性; 3）缺乏体外 细胞毒性或巨噬细胞活化; 4）在二度烧伤时通过体内溶解按需去除， 半胱氨酸甲酯溶液的应用; 5）预防体内二度烧伤中的细菌感染; 6)与传统绷带相比，具有可比的和趋势性的愈合优势;以及，7）容易“喷雾- 在覆盖人手的复杂表面、手指和蹼中的“开/喷”用途。的最终目标 拟议项目是为HydrAid烧伤敷料获得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的关键Go/No-Go里程碑：1）制造，2） 实验室和动物试验，3）人为因素（非临床）可用性试验，和4）法规事务。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.）为目标2和目标3的评价提供成品。目标2：确认 在大面积烧伤中，HydrAid烧伤敷料优于传统敷料， ISO 10993安全性和生物相容性试验。目标3：进行人为因素和非临床可用性测试 并制定标签，包括使用说明书。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510（k）。成功 这些目标的完成将使Ionic Pharma能够开始生产、营销和销售HydrAid。