A Novel Opioid-Free Targeted Pain Control Method for Acute Post-Operative Localized Pain Related to Oral Surgical Procedures

一种新型无阿片类药物靶向疼痛控制方法，用于治疗与口腔手术相关的急性术后局部疼痛

• 批准号: 9908492
• 负责人: Rahul Jadia
• 金额: $ 30万
• 依托单位: REVBIO, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-19 至 2021-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908492
• 关键词: Absence of pain sensation; Accounting; Acute; Acute pain management; Address; Adhesives; Aliquot; Analgesics; Anesthetics; Biocompatible Materials; Biological Assay; Bone Regeneration; Bupivacaine; Canis familiaris; Categories; Cell Survival; Cessation of life; Chemical Structure; Chromatography; Clinical; Conduct Clinical Trials; Cyclic GMP; Dental Care; Dental Implants; Diagnosis; Diffusion; Dose; Drug Addiction; Drug Formulations; Drug Targeting; Ensure; Environmental Irritants; Excision; Filler; Formulation; High Pressure Liquid Chromatography; Human; Implant; In Vitro; Incidence; Incubated; Injury; Jaw; Lead; Left; Local Anesthetics; Medical; Methods; Minerals; Modeling; Naproxen; Operative Surgical Procedures; Opioid; Oral Surgeon; Oral Surgical Procedures; Orthopedic Procedures; Osteitis; Osteoblasts; Outpatients; Overdose; Pain; Pain management; Patients; Performance; Pharmaceutical Preparations; Phase; Physiological; Postoperative Pain; Postoperative Period; Property; Replacement Arthroplasty; Risk; Route; Sampling; Site; Spinal Fusion; Techniques; Technology; Temperature; Testing; Therapeutic; Time; Tissues; Tooth Extraction; Trauma; base; biomaterial compatibility; bone; cytotoxicity; dosage; drug candidate; illicit opioid; improved; in vivo; innovation; manufacturing process; non-opioid analgesic; novel; novel strategies; opioid abuse; opioid use; overdose death; pain relief; pregabalin; prescription opioid; prescription opioid misuse; prevent; reconstruction; regenerative; seal; side effect; technology development; wisdom tooth; wound

Project Summary/Abstract Drug addiction and overdose are a major problem in the US, accounting for 70,237 deaths in 2017. Over 60% of drug overdose deaths involved misuse of prescription or illicit opioids, and 30% of opioid prescriptions are written following oral surgical or dental procedures. Approximately 10 million wisdom teeth are removed annually. A statistically significant 6.8% absolute risk increase in persistent opioid use and a 5.4% increase in the subsequent diagnosis of opioid abuse follows a single course of opiates following wisdom tooth extraction. Therefore, there is a compelling need to develop a front line, non-opioid-based acute pain management strategy for outpatient oral surgical procedures. LaunchPad Medical has developed Tetranite® (TN), a novel bone regenerative mineral-organic self-setting adhesive biomaterial. TN has been extensively studied in vivo in a canine jaw model and shown to be effective and well-tolerated. Additionally, preliminary in vitro studies have shown that medication can be incorporated into TN formulations and released over time, and it is well established that the release profile of a target drug can be tailored to time-dose curve using conventional time release technology such as passive diffusion. Administering locally-acting analgesics (e.g., naproxen), local anesthetics (e.g., bupivacaine) and/or gabapentinoids (e.g., pregabalin) passively released over the 5-day window when pain relief is most needed, is a strong and innovative strategy for limiting acute postoperative pain following wisdom tooth removal, while employing TN as a filler/sealant will allow for simultaneous occlusion of environmental irritants to the bone wound, thus preventing osteitis and allowing bone regeneration. In this Phase I project, we will demonstrate that drug-loaded TN can be a novel route to providing localized and time release pain medication following wisdom tooth extraction by determining the release profile of various pain medications from TN at different concentrations (Aim I), verifying the consistency of TN handling and exotherm in compounded formulations (Aim II), and verifying the biocompatibility of TN-drug formulation in vitro using human osteoblasts (Aim III). The ability to release pain therapeutics in a controlled fashion and directly at the site of injury offers improved pain control following oral surgical procedures without exposing the patient to opioids. In addition, this novel approach to pain management can be extended to more invasive orthopedic procedures such as joint replacement, spinal fusions or reconstructive trauma surgery. In Phase II we will conduct an in vivo study to assess efficacy of medicated TN to address post-operative pain following wisdom tooth odontectomy, optimize incorporation and release of medications in TN formulations, develop cGMP manufacturing process for the compounded product, and ultimately conduct clinical trials for bone void filler using medicated TN.

项目摘要/摘要 吸毒和吸毒过量是美国的一个主要问题，2017年导致70237人死亡。超过60% 药物过量死亡涉及滥用处方或非法阿片类药物，30%的阿片类药物处方是 在口腔外科或牙科手术后写成的。每年大约有1000万颗智齿被拔掉。 持续使用阿片类药物的绝对风险在统计上显著增加6.8%，在 随后被诊断为阿片类药物滥用的是智齿拔除后的一个阿片类药物疗程。 因此，迫切需要制定一种前线的、非阿片类药物的急性疼痛管理策略。 用于门诊口腔外科手术。 LaunchPad Medical开发出一种新型骨再生矿物--有机自固化材料Tetranite®(TN 粘附性生物材料。TN已经在犬下颌模型中进行了广泛的活体研究，并被证明是有效的 而且耐受性很好。此外，初步的体外研究表明，药物可以合并到 TN配方并随时间释放，并且很好地建立了靶向药物的释放曲线可以是 使用被动扩散等传统的时间释放技术为时间-剂量曲线量身定做。管理 局部作用的镇痛剂(例如，萘普生)、局部麻醉剂(例如，布比卡因)和/或加巴喷丁(例如， 普瑞巴林)在最需要止痛的5天窗口内被动释放，是一种强有力的创新 限制智齿拔除术后急性疼痛的策略，同时使用TN作为 填充剂/密封剂将允许同时封闭骨伤口的环境刺激物，从而防止 骨炎并允许骨骼再生。 在这个第一阶段的项目中，我们将展示载药TN可以是一种新的途径，以提供本地化和 智齿拔除后不同类型疼痛缓释药物的缓释作用 来自不同浓度TN的药物(目标I)，验证TN处理和放热的一致性 在复方制剂中(AIM II)，并验证TN-药物制剂的体外生物相容性 人成骨细胞(AIM III)。能够以受控的方式直接释放止痛药 损伤部位改善了口腔外科手术后的疼痛控制，而不会使患者暴露在 阿片类药物。此外，这种新的疼痛管理方法可以扩展到更具侵入性的骨科 关节置换、脊柱融合或重建创伤手术等手术。在第二阶段，我们将 进行体内研究，以评估药物TN治疗术后疼痛的疗效 牙齿切除，优化TN配方中药物的并入和释放，开发cGMP 复合产品的制造工艺，并最终进行骨空洞填充物的临床试验 用药的TN。