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. 抽象的索诺兰生物科学公司 SBIR PA-21-259：第一阶段美国每年约有 1,400 万例手术与中度至严重的术后疼痛在休息时持续至少三天。据报道，疼痛是其中之一住院手术后延迟出院的最常见原因以及门诊手术后计划外入院。术后疼痛的治疗对临床医生来说是一个具有挑战性的场景，因为它是资源密集型的并且频繁涉及与不良反应相关的阿片类药物。而且，较差控制疼痛会导致患者痛苦并增加并发症的风险。目前的最佳实践支持使用多模式镇痛方案，该方案依赖于多种药物来抵消对阿片类药物的需求。局部麻醉剂是关键组成部分多模式镇痛，因为它们可以有效减轻局部区域的疼痛，同时具有良好的安全性。不幸的是，局部麻醉分子仅保持活性长达 8 小时，可用的缓释产品在超过 12-24 小时后功效有限术后。市场领导者是 Exparel（布比卡因脂质体），该产品有望达到 2021 年销售额将达到 5 亿美元。仍然存在巨大的需求和商业机会局部麻醉剂可提供至少三天的镇痛效果，并会持续到手术后家庭环境，可能使患者无需阿片类药物处方即可安全出院。我们开发了一种专有的缓释载体SB Gel，它可以混合使用时与局部麻醉剂布比卡因一起并以水溶液形式施用在手术部位形成软凝胶。 SB Gel 提供基于扩散的布比卡因释放多天并在约三周内在体内溶解。在猪皮肤和肌肉切口模型中，负载布比卡因的 SB Gel 可提供持续 120 小时的镇痛效果。力明显更大与接受 SB Gel + 布比卡因治疗的部位相比，接受 SB Gel + 布比卡因治疗的部位对切口处的耐受性术后 24、48、72、96 和 120 小时进行排气。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- 加载 SB Gel 作为同类最佳的缓释局部麻醉剂。在目标 1 中，我们将研究 SB Gel + 布比卡因的剂量反应，比较 SB Gel + 布比卡因的有效性针对所有 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、全身暴露布比卡因，以及对肌肉和周围神经的毒性。项目顺利完成将为扩大生产规模和未来支持 IND 的毒理学研究做好准备。