Prolonged Analgesia in Rodents

描述（由申请方提供）：实验动物经常经历各种痛苦的外科手术以及非外科手术。所有参与实验动物护理和使用的研究人员都有伦理义务通过使用镇痛剂减轻或最好消除疼痛和痛苦，前提是这些镇痛剂不干扰研究目的。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，以最大限度地减少或消除动物在经历痛苦程序时的疼痛和痛苦。在涉及疼痛过程的各种研究中，最广泛使用的实验室动物是啮齿动物。文献综述表明，丁丙诺啡是啮齿类动物中应用最广泛的麻醉性镇痛药，因为其镇痛活性好，作用持续时间长。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，需要反复胃肠外给予丁丙诺啡，这是一个对动物固有压力的过程。为了减少处理频率，进而改善治疗动物的健康状况，我们建议开发一种丁丙诺啡长效制剂，其能够在单次皮下给药制剂后在小鼠和大鼠中维持镇痛3至5天。该长效制剂将是丁丙诺啡碱在适当的药学上可接受的可注射的水混溶性溶剂/媒介物中的溶液。在皮下注射时，当丁丙诺啡溶液中的水混溶性溶剂/溶媒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将能够在啮齿动物中维持镇痛持续较长时间（3-5天）。这样的制剂不仅通过减少给药频率和对动物的应激而显著改善动物的健康，而且还为兽医及其工作人员治疗动物节省了相当多的时间。如果该制剂获得成功，可用于其他实验室动物，如兔、仓鼠、豚鼠、猫、犬、猪和非人灵长类动物，并进行适当的剂量调整。丁丙诺啡的新型长效制剂在单次皮下注射后将能够在啮齿动物中维持镇痛至少3天。这种制剂将通过减少给药频率和对动物的压力来改善动物的健康，并为兽医及其工作人员治疗动物节省大量时间。如果该制剂成功，则可通过适当的剂量调整用于其他实验室动物。

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.