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（由申请人提供）：实验动物经常要接受各种痛苦的外科手术和非外科手术。通过使用镇痛药来减少或最好消除疼痛和痛苦是所有参与实验动物护理和使用的研究人员的道德义务，前提是这些镇痛药不干扰研究目标。此外，机构动物护理和使用委员会 (IACUC) 必须确保使用适当的麻醉剂和/或镇痛剂，以最大程度地减少或消除经历痛苦手术的动物的疼痛和困扰。在涉及疼痛过程的各种类型的研究中，最广泛使用的实验动物是啮齿动物。对现有文献的调查表明，丁丙诺啡因其优异的镇痛活性和作用持续时间而成为啮齿类动物使用最广泛的麻醉镇痛药。此外，与吗啡不同，呼吸抑制通常不是这种阿片类药物的问题。然而，为了提供足够的镇痛作用，需要反复肠胃外施用丁丙诺啡，这一过程对动物来说本身就有压力。为了减少处理频率，从而改善接受治疗的动物的健康，我们建议开发一种长效丁丙诺啡制剂，在单次皮下注射该制剂后，能够在小鼠和大鼠中维持镇痛 3 至 5 天。这种长效制剂是丁丙诺啡碱在适当的药学上可接受的、可注射的、与水混溶的溶剂/载体中的溶液。皮下注射时，当丁丙诺啡溶液中的水混溶性溶剂/载体在注射部位被吸收或被水性体液带走时，丁丙诺啡碱将在注射部位沉淀，因为其水溶性差。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类动物中维持较长时间（3-5 天）的镇痛作用。这种配方不仅可以通过减少给药频率和对动物的压力来显着改善动物的健康，而且还可以为兽医及其工作人员治疗动物节省大量时间。如果该配方成功，可通过适当的剂量调整用于其他实验动物，如兔子、仓鼠、豚鼠、猫、狗、猪和非人类灵长类动物。丁丙诺啡的新型长效制剂在单次皮下注射后能够在啮齿类动物中维持镇痛至少 3 天。这种配方将通过减少给药频率和对动物的压力来改善动物的健康，并为兽医及其治疗动物的工作人员节省大量时间。如果该配方成功，可通过适当的剂量调整用于其他实验动物。