Sustained-release gel for multi-day control of postoperative pain

用于多天控制术后疼痛的缓释凝胶

• 批准号: 10481881
• 负责人: Derek James Overstreet
• 金额: $ 25.96万
• 依托单位: SONORAN BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-06 至 2024-06-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10481881
• 关键词: Absence of pain sensation; Acetates; Activities of Daily Living; Adverse effects; Analgesics; Area; Biological Sciences; Body Temperature; Bupivacaine; Caring; Clinical Data; Clinical Research; Collagen; Conflict (Psychology); Data; Diffusion; Disadvantaged; Dose; Drug Kinetics; Economic Burden; Excipients; Exposure to; FDA approved; Family suidae; Formulation; Foundations; Future; Gel; Goals; Health Personnel; Histopathology; Home; Hospitalization; Hospitals; Hour; Implant; Infiltration; Injections; Inpatients; Lead; Liposomes; Local Anesthetics; Medicare; Medication Management; Methods; Modeling; Monitor; Morphine; Motion; Muscle; Nerve Block; Non-Steroidal Anti-Inflammatory Agents; Numbness; Operative Surgical Procedures; Opioid; Oral; Outpatients; Pain; Pain management; Patients; Peripheral Nerves; Persistent pain; Pharmaceutical Preparations; Phase; Postoperative Pain; Postoperative Period; Prevention; Principal Investigator; Procedures; Pump; Readiness; Recommendation; Regimen; Rehabilitation therapy; Reporting; Resources; Rest; Risk; Safety; Sales; Saline; Self Care; Site; Skin; Small Business Innovation Research Grant; Sucrose; Surgical Wound Infection; Surgical incisions; Surveys; Syringes; Time; Tissues; Toxic effect; Toxicology; United States; Work; addiction; antimicrobial; aqueous; base; clinically significant; compare effectiveness; experience; genotoxicity; high risk; hospital readmission; in vivo; infection risk; manufacturing scale-up; meloxicam; multimodality; non-opioid analgesic; novel; opioid use; pain reduction; pain sensation; payment; prescription opioid; response; safety study; side effect; systemic toxicity; time use; treatment duration; wound healing

Principal Investigator: Overstreet, Derek J. Abstract Sonoran Biosciences, Inc. SBIR PA-21-259: Phase I About 14 million surgeries annually in the United States are associated with moderate-to- severe postoperative pain lasting at least three days at rest. Pain has been reported to be one of the most common reasons for delayed discharge following inpatient procedures and for unplanned hospital admissions following outpatient procedures. Treatment of postoperative pain presents a challenging scenario for clinicians because it is resource-intensive and frequently involves opioid medications which are associated with adverse effects. Moreover, poorly managed pain leads to patient suffering and increased risks of complications. Current best practices support the use of multimodal analgesia regimens which rely on multiple classes of drugs to offset the need for opioids. Local anesthetics are a critical component of multimodal analgesia because they can provide a potent reduction of pain in a local area while having a favorable safety profile. Unfortunately, local anesthetic molecules only remain active for up to eight hours and available extended-release products have limited efficacy beyond 12-24 hr postoperatively. The market leader is Exparel (liposomal bupivacaine), which is on pace to reach $500 million in sales in 2021. There remains a significant need and commercial opportunity for a local anesthetic that provides analgesia for at least three days, which would carry over into the home setting, potentially enabling patients to be discharged safely without opioid prescriptions. We have developed a proprietary sustained-release carrier, SB Gel, which can be mixed with the local anesthetic bupivacaine at the time of use and applied as an aqueous solution that forms a soft gel in the surgical site. SB Gel provides diffusion-based release of bupivacaine over multiple days and dissolves in vivo in about three weeks. In a pig skin and muscle incision model, bupivacaine-loaded SB Gel provided analgesia lasting for 120 hours. Significantly greater force at the incision was tolerated in sites receiving SB Gel + bupivacaine compared to those receiving Exparel at 24, 48, 72, 96, and 120 hours postoperatively. We now propose to complete a Phase 1 project to establish the feasibility of bupivacaine- loaded SB Gel as the best-in-class extended-release local anesthetic. In Aim 1, we will study the dose response of SB Gel + bupivacaine, compare the effectiveness of SB Gel + bupivacaine against all of the FDA-approved extended-release local anesthetics, and evaluate effects on wound healing. In Aim 2, we will evaluate safety, including systemic toxicity, systemic exposure to bupivacaine, and toxicity to muscle and peripheral nerves. Successful completion of the project will result in readiness for scaled-up manufacturing and future IND-enabling toxicology studies.

主要研究者：Overstreet，Derek J。 摘要 Sonoran Biosciences，Inc. SBIR PA-21-259：I期 在美国，每年约有1400万例手术与中度至 术后严重疼痛，休息时至少持续3天。据报道，疼痛是 住院手术后延迟出院的最常见原因， 门诊手术后的计划外住院。术后疼痛的治疗 为临床医生提出了一个具有挑战性的方案，因为它是资源密集型的，并且经常 涉及与副作用相关的阿片类药物。此外，差 控制疼痛导致患者痛苦和增加并发症的风险。 目前的最佳实践支持使用多模式镇痛方案， 多类药物以抵消对阿片类药物的需求。局部麻醉剂是 多模式镇痛，因为它们可以有效地减少局部疼痛， 具有良好的安全性。不幸的是，局部麻醉剂分子只有在 长达8小时，而现有的缓释产品在12-24小时后的疗效有限 手术后。市场的领导者是Exparel（脂质体布比卡因），这是步伐，以达到 2021年销售额5亿美元。仍然存在着巨大的需求和商业机会， 局部麻醉，提供镇痛至少三天，这将携带到 家庭环境，可能使患者能够安全出院，无需阿片类药物处方。 我们开发了一种专有的缓释载体SB Gel， 与局部麻醉剂布比卡因一起使用，并作为水溶液施用， 在手术部位形成软凝胶。SB凝胶提供布比卡因的基于扩散的释放， 几天，并在体内溶解约三周。在猪皮肤和肌肉切口模型中， 载布比卡因SB凝胶提供持续120小时的镇痛。更大的力量 与接受SB凝胶+布比卡因的部位相比，接受SB凝胶+布比卡因的部位对切口的耐受性 在术后24、48、72、96和120小时脱衣服。 我们现在建议完成第一阶段项目，以确定布比卡因的可行性- 装载SB凝胶作为一流的缓释局部麻醉剂。在目标1中，我们将研究 SB凝胶+布比卡因的剂量反应，比较SB凝胶+布比卡因的有效性 对所有FDA批准的缓释局部麻醉剂，并评估对 伤口愈合在目标2中，我们将评估安全性，包括全身毒性、全身暴露 以及对肌肉和周围神经的毒性。成功完成项目 将为扩大生产规模和未来的IND毒理学研究做好准备。