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

基本信息

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
项目类别：
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

项目摘要

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.

首席研究员：Overstreet，Derek J. 抽象的 Sonoran Biosciences，Inc。 SBIR PA-21-259：第一阶段美国每年约有1400万辆手术与中度至中等相关严重的术后疼痛至少持续三天。据报道疼痛是在住院程序后延迟出院的最常见原因和遵循门诊手术的计划外医院入院。治疗术后疼痛为临床医生带来了一个具有挑战性的情况，因为它是资源密集的，并且经常涉及与不良反应有关的阿片类药物。而且，很差托管疼痛会导致患者痛苦和并发症的风险增加。当前的最佳实践支持依靠多模式镇痛方案的使用多种类药物以抵消对阿片类药物的需求。局部麻醉是关键的组成部分多模式镇痛，因为它们可以在局部提供有效的疼痛，而具有良好的安全性。不幸的是，局部麻醉分子仅保持活跃长达八个小时，可用的扩展释放产品的功效有限，超过12-24小时术后。市场领导者是Exparel（脂质体布比卡因），它正在努力达到 2021年的销售额为5亿美元。仍然有很大的需求和商业机会提供至少三天的镇痛的局部麻醉剂，这将延续到家庭环境，可能使患者在没有阿片类药物处方的情况下安全出院。我们已经开发了专有的持续释放载体SB凝胶，可以混合使用局部麻醉布比卡因在使用时，并用作水溶液在手术部位形成软凝胶。 SB凝胶提供基于扩散的布比卡因的释放多天，大约三个星期内溶解体内。在猪皮和肌肉切口模型中布比卡因加载的SB凝胶提供了持续120小时的镇痛。力量明显更大在接收SB凝胶 +布比卡因的现场，在切口处被耐受术后24、48、72、96和120小时的Exparel。现在，我们建议完成一项第一阶段项目，以确定布比卡因的可行性加载SB凝胶作为一流的扩展释放局部麻醉剂。在AIM 1中，我们将研究 SB凝胶 + bupivacaine的剂量反应，比较SB凝胶 + Bupivacaine的有效性针对所有经FDA批准的扩展释放局部麻醉药，并评估对伤口愈合。在AIM 2中，我们将评估安全性，包括全身毒性，全身暴露到布比卡因，对肌肉和周围神经的毒性。成功完成项目将准备好制造规模的制造和未来的毒理学研究。