Prolonged Analgesia in Rodents

啮齿类动物的长期镇痛

• 批准号: 7329096
• 负责人: JAMES R JOHNSON
• 金额: $ 9.85万
• 依托单位: ATLANTIC PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2009-03-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7329096
• 关键词: Absence of pain sensation; Analgesics; Anesthetics; Animal Rights; Animals; Annual Reports; Arthritis; Birds; Blood specimen; Body Fluids; Buprenorphine; Canis familiaris; Caring; Cavia; Development; Distress; Dosage Forms; Dose; Drug Formulations; Educational process of instructing; Family suidae; Feasibility Studies; Felis catus; Frequencies; Future; Hamsters; Hour; IACUC; Injectable; Injection of therapeutic agent; Investigation; Laboratory Animals; Laparotomy; Legal patent; Literature; Maintenance; Marketing; Measurement; Methods; Morphine; Mus; Narcotic Analgesics; Numbers; Operative Surgical Procedures; Opioid; Orthopedic Procedures; Oryctolagus cuniculus; PEO-400; Pain; Personal Satisfaction; Pharmaceutical Preparations; Plasma; Polychloroterphenyl Compounds; Polyethylene Glycols; Prevention, Clinical, and Therapeutic Subcommittee; Procedures; Process; Pyrrolidinones; Range; Rattus; Reporting; Research; Research Personnel; Rights; Rodent; Secure; Site; Solubility; Solutions; Solvents; Stress; Subcutaneous Injections; Surveys; Sus scrofa; Suspending Agents; Suspension substance; Suspensions; Tail; Technology; Technology Assessment; Temperature; Testing; Thoracotomy; Time; Tranquilizing Agents; Treatment Cost; United States; Ventilatory Depression; Veterinarians; Water; Week; aqueous; base; commercialization; day; ethyl citrate; glycofurol; improved; in vivo; intravenous injection; nonhuman primate; novel; subcutaneous

DESCRIPTION (provided by applicant): Laboratory animals are often subjected to various painful surgical procedures as well as non-surgical procedures. It is the ethical obligation of all research personnel involved with the care and use of laboratory animals to reduce or preferably eliminate pain and distress by using analgesics, provided these analgesics do not interfere with the research objectives. Furthermore, the Institutional Animal Care and Use Committee (IACUC) must assure that appropriate anesthetics and/or analgesics are used to minimize or eliminate pain and distress for animals undergoing painful procedures. The most widely used laboratory animals for various types of research involving painful procedures are rodents. A survey of current literature indicates that buprenorphine is the most widely used narcotic analgesic for rodents because of its excellent analgesic activity and long duration of action. Moreover, unlike morphine, respiratory depression is not usually a problem with this opioid. However, to provide adequate analgesia, repeated parenteral administration is required for buprenorphine, a process that is inherently stressful to the animals. In order to reduce the frequency of handling and in turn, improve the well being of the animals under treatment, we propose to develop a long-acting formulation of buprenorphine that is capable of maintaining analgesia in mice and rats for 3 to 5 days following a single subcutaneous administration of the formulation. This long acting formulation will be a solution of buprenorphine base in an appropriate pharmaceutically acceptable, injectable, water-miscible solvents/vehicles. Upon subcutaneous injection, the buprenorphine base will precipitate at the injection site because of its poor aqueous solubility when the water-miscible solvent/vehicle in the buprenorphine solution is absorbed at the injection site or is carried away by the aqueous body fluid. The underlying hypothesis of our research is that a long acting formulation of buprenorphine will be able to maintain analgesia in rodents for a prolonged period of time (3-5 days) following a single subcutaneous injection. Such a formulation will not only significantly improve the well being of animals by reducing the dosing frequency and stress to the animals, but also save considerable time for veterinarians and their staff treating the animals. If this formulation is successful, it could be used for other laboratory animals such as rabbits, hamsters, guinea pigs, cats, dogs, pigs and non-human primates with appropriate dose adjustment. The novel long acting formulation of buprenorphine will be able to maintain analgesia in rodents for at least 3 days following a single subcutaneous injection. Such a formulation will improve the well-being of animals by reducing the dosing frequency and stress to the animals, and save considerable time for veterinarians and their staff treating the animals. If this formulation is successful, it could be used for other laboratory animals with appropriate dose adjustment.

描述(申请人提供)：实验动物经常经历各种痛苦的手术程序以及非手术程序。所有参与照料和使用实验动物的研究人员都有道德义务通过使用镇痛剂来减少或最好消除疼痛和痛苦，前提是这些镇痛剂不会干扰研究目标。此外，机构动物保护和使用委员会(IACUC)必须确保使用适当的麻醉剂和/或镇痛剂，以最大限度地减少或消除正在进行痛苦手术的动物的痛苦和痛苦。在涉及痛苦程序的各种研究中，最广泛使用的实验室动物是啮齿动物。对现有文献的调查表明，丁丙诺啡具有良好的镇痛活性和较长的作用时间，是目前应用最广泛的啮齿动物麻醉性镇痛剂。此外，与吗啡不同，这种阿片类药物通常不会出现呼吸抑制的问题。然而，为了提供足够的止痛，丁丙诺啡需要反复静脉给药，这一过程对动物来说是固有的压力。为了减少处理的次数，进而改善接受治疗的动物的健康状况，我们建议开发一种丁丙诺啡长效制剂，该制剂能够在小鼠和大鼠皮下一次性给药后维持3-5天的止痛。这一长效配方将是丁丙诺啡碱在适当的药学上可接受的、可注射的、可溶于水的溶剂/载体中的溶液。在皮下注射时，丁丙诺啡溶液中的水溶性溶剂/载体在注射部位被吸收或被含水体液带走时，丁丙诺啡基质会在注射部位沉淀，因为丁丙诺啡基质的水溶解性较差。我们研究的基本假设是，丁丙诺啡的长效制剂在单次皮下注射后能够在啮齿动物体内维持较长时间(3-5天)的止痛。这样的配方不仅可以通过减少给药频率和对动物的压力来显著改善动物的健康，而且还可以为兽医和他们的工作人员节省相当多的时间来治疗动物。如果该配方成功，通过适当的剂量调整，它可以用于其他实验动物，如兔子、仓鼠、豚鼠、猫、狗、猪和非人类灵长类动物。丁丙诺啡这种新的长效制剂在一次皮下注射后，将能够在啮齿动物身上保持至少3天的止痛。这样的配方将通过减少给药频率和对动物的压力来改善动物的福祉，并为兽医和他们的工作人员节省大量治疗动物的时间。如果该配方研制成功，可在适当调整剂量的情况下用于其他实验动物。