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; 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 吸毒成瘾和过量是美国的主要问题，2017年占70,237人的死亡。超过60％ 药物过量死亡涉及滥用处方或非法阿片类药物，而30％的阿片类药物处方为 以口腔外科或牙科手术为书面。每年将大约1000万个智慧牙齿去除。 具有统计学意义的6.8％的绝对风险增加了持续使用的阿片类药物，并增加了5.4％ 随后诊断阿片类药物滥用是在智慧拔牙后的单一过程之后进行的。 因此，迫切需要开发前线，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开发了Tetranite®（TN），这是一种新型的骨骼再生矿物有机自我设定 粘合生物材料。 TN已在犬颌模型中进行了广泛研究，并证明是有效的 和耐受性良好。此外，初步的体外研究表明，可以将药物纳入 TN公式并随着时间的推移发布，并且可以很好地确定目标药物的发布曲线可以是 使用常规的时间释放技术（例如被动扩散）量身定制为时间剂量曲线。管理 局部作用镇痛药（例如萘普生），局部麻醉药（例如，布比卡因）和/或gabapentinoids（例如 当最需要缓解疼痛时，pregabalin）在5天的窗户上被动释放，这是一种强大而创新的 在脱牙后限制急性演示者疼痛的策略，同时采用TN作为 填充/密封剂将使骨骼伤口简单地阻塞环境刺激剂，从而防止 骨炎并允许骨再生。 在这个阶段的项目中，我们将证明，装有药物的TN可以是提供本地化和的新途径 通过确定各种疼痛的释放概况，时间释放止痛药在智力拔牙后 TN以不同浓度的药物（AIM I）验证TN处理和放热的一致性 在复合公式（AIM II）中，并在体外验证TN-prug公式的生物相容性 人类成骨细胞（AIM III）。以受控方式释放疼痛疗法的能力，直接在 受伤部位可改善疼痛控制之后口腔外科手术，而无需暴露患者 OOPIOIDS。此外，这种新颖的疼痛管理方法可以扩展到更具侵入性的骨科 诸如关节置换，脊柱融合或重建创伤手术之类的程序。在第二阶段，我们将 进行体内研究，以评估智慧后术后疼痛的效率以解决术后疼痛 牙齿牙齿切除术，优化纳入政策和在TN配方中的药物释放，发展CGMP 复合产品的制造过程，并最终使用骨无效填充剂进行临床试验 药田。