Prolonged Analgesia in Rodents

描述（由申请人提供）：实验动物经常遭受各种痛苦的外科手术和非外科手术。所有参与实验动物护理和使用的研究人员都有道德义务通过使用镇痛药来减少或最好消除疼痛和痛苦，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/或镇痛药，以尽量减少或消除动物经历痛苦过程的疼痛和痛苦。在涉及痛苦过程的各种研究中，最广泛使用的实验动物是啮齿动物。文献综述表明，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药。此外，与吗啡不同，这种阿片类药物通常不会造成呼吸抑制问题。然而，为了提供足够的镇痛，需要反复肠外给药丁丙诺啡，这一过程对动物本身是有压力的。为了减少处理的频率，从而改善治疗中的动物的健康，我们建议开发一种长效丁丙诺啡配方，能够在单次皮下给药后在小鼠和大鼠中维持3至5天的镇痛作用。这种长效制剂将是丁丙诺啡碱的溶液，在适当的药学上可接受的，可注射的，水混溶的溶剂/载体中。皮下注射后，丁丙诺啡溶液中的水混溶溶剂/载体在注射部位被吸收或被水溶液带走时，丁丙诺啡碱的水溶性较差，因此会在注射部位沉淀。我们研究的基本假设是，丁丙诺啡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。这样的配方不仅可以通过减少给药频率和动物的压力来显著改善动物的健康状况，而且可以节省兽医及其工作人员治疗动物的大量时间。如果该配方成功，可用于其他实验动物，如兔子、仓鼠、豚鼠、猫、狗、猪和非人灵长类动物，并进行适当的剂量调整。新型长效丁丙诺啡制剂将能够在单次皮下注射后在啮齿动物中维持至少3天的镇痛作用。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健康，并节省兽医及其工作人员治疗动物的大量时间。如果该制剂成功，可通过适当的剂量调整用于其他实验动物。

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.