Multi-day Pain Management Therapy with Novel Injectable Formulation

采用新型注射制剂的多日疼痛管理疗法

• 批准号: 8198342
• 负责人: Cory Berkland
• 金额: $ 25.37万
• 依托单位: ORBIS BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8198342
• 关键词: Address; Analgesics; Animals; Breakthrough Pain; Businesses; Canis familiaris; Characteristics; Chronic; Data; Development; Dose; Drug Formulations; Economic Burden; Encapsulated; Frequencies; Goals; Gold; Head; Health Personnel; Hour; In Vitro; Incentives; Industry; Infusion Pumps; Injectable; Kinetics; Maintenance; Marketing; Methods; Microspheres; Opioid; Pain; Pain management; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Population; Positioning Attribute; Preparation; Principal Investigator; Production; Proteins; Provider; Public Health; Reliance; Reporting; Research; Resistance; Risk; Sesame Oil; Solutions; Subcutaneous Injections; Technology; Therapeutic; Tramadol; United States; Validation; Variant; Work; addiction; chronic pain; compliance behavior; controlled release; cost; drug efficacy; drug production; experience; health economics; improved; in vivo; innovation; novel; opioid abuse; particle; success; therapy development

DESCRIPTION (provided by applicant): Our long term goal is to widespread the use of PPF technology for promoting effective production of drug-encapsulating microparticles with uniform size and physical characteristics that can be leveraged to release a specific drug at controlled rates over multi-day periods in vivo after a single administration. For this proposal, we are specifically targeting a cost and dose-effective management of chronic pain with precisely tailored drug release characteristics. Chronic pain afflicts a large population in United States. Extended release formulations of safer (unscheduled) opioids can improve patient compliance and drug efficacy, and can limit the possibility of breakthrough pain, all without putting the patients at the risk of addiction. However, existing extended release opioid formulations are insufficient, and are limited to providing relief up to a maximum of 24 h. Using tramadol, an unscheduled opioid, this project aims to create a long-acting (up to 5-day) tramadol formulation in an injectable form to enhance pain relief and fill a critical innovation gap in the pharmaceutical market. The specific objective of this application is to optimize tramadol-loaded microspheres produced by PPF technology with a 5 day zero-order drug release profiles, imitating a constant infusion pump-like dosing (Specific Aim 1), and validate the results achieved with extended release formulations of tramadol in vivo (Specific Aim 2). Our overall hypothesis is that extended pain management therapy developed using uniform microspheres produced by PPF technology will offer a cost and dose-effective management of chronic pain with precisely tailored drug release characteristics, which will provide a more controlled and predictable drug release compared to tramadol-loaded microspheres fabricated using conventional methods, and significantly improve controlled release characteristics compared to contemporary commercially-available sustained-release pain management products (e.g., ULTRAM(R)). Multi-day chronic pain management therapy holds the potential to provide a revolutionary alternative for pain management. PUBLIC HEALTH RELEVANCE: Chronic pain afflicts a large population in United States. Extended release formulations of safer (unscheduled) opioids can improve patient compliance and drug efficacy, and can limit the possibility of breakthrough pain, all without putting the patients at the risk of addiction. However, existing extended release opioid formulations are insufficient, and are limited to providing relief up to a maximum of 24 h. Using tramadol, an unscheduled opioid, this project aims to create a long- acting (up to 5-day) tramadol formulation in an injectable form to enhance pain relief and fill a critical innovation gap in the pharmaceutical market.

描述（由申请人提供）：我们的长期目标是广泛使用 PPF 技术，以促进有效生产具有均匀尺寸和物理特性的药物封装微粒，这些微粒可用于在多天内以受控速率释放特定药物单次给药后体内的时间。对于该提案，我们的具体目标是通过精确定制的药物释放特性，对慢性疼痛进行成本有效、剂量有效的管理。在美国，慢性疼痛困扰着大量人口。更安全（非预定）阿片类药物的缓释制剂可以提高患者的依从性和药物疗效，并可以限制突发性疼痛的可能性，所有这些都不会使患者面临成瘾的风险。然而，现有的缓释阿片类制剂是不够的，并且仅限于提供最多 24 小时的缓解。该项目旨在使用曲马多（一种非预定阿片类药物）开发一种注射形式的长效（长达 5 天）曲马多制剂，以增强疼痛缓解并填补制药市场的关键创新空白。该应用的具体目标是优化 PPF 技术生产的曲马多微球，具有 5 天零级药物释放曲线，模拟恒定输注泵式给药（具体目标 1），并验证缓释所取得的结果曲马多体内制剂（具体目标 2）。我们的总体假设是，使用 PPF 技术生产的均匀微球开发的扩展疼痛管理疗法将为慢性疼痛提供成本有效、剂量有效的管理，并具有精确定制的药物释放特性，与曲马多相比，这将提供更受控和可预测的药物释放。使用传统方法制造的负载微球，与当代市售缓释疼痛管理产品（例如 ULTRAM®）相比，显着改善了控释特性。多日慢性疼痛管理疗法有可能为疼痛管理提供革命性的替代方案。 公共卫生相关性：慢性疼痛困扰着美国大量人口。更安全（非预定）阿片类药物的缓释制剂可以提高患者的依从性和药物疗效，并可以限制突发性疼痛的可能性，所有这些都不会使患者面临成瘾的风险。然而，现有的缓释阿片类制剂是不够的，并且仅限于提供最多 24 小时的缓解。该项目旨在使用曲马多（一种非预定阿片类药物）创建一种注射形式的长效（长达 5 天）曲马多制剂，以增强疼痛缓解并填补制药市场的关键创新空白。