Abstract：
Metamizole easily decomposes in the body and has a short action time and low bioavailability. Hence, frequent injection administrations are needed to maintain its plasma concentration. This study aimed to design and develop an in-situ gel based on poloxamer 407 and 188 to assess its long-acting antipyretic effects. The in-situ gel-forming systep00m with optimum sol-gel transition temperature of 35.9 °C to 36.3 °C could be formed using a combination of P407 at a ratio of 21-23% (w/v) and P188 at a ratio of 2-4% (w/v). In vitro erosion test showed that the in-situ gel\'s erosion curve and the metamizole release rate both reached about 90% at 6 h, revealing a good linear relationship between the in-situ gel erosion and the drug release. In vitro release test with dialysis tube showed that the release of metamizole from the in-situ gel was remarkably slower than that from the metamizole solution. Approximately 85% of metamizole was released in the dialysis tube within 7 h, implying a good sustained release effect. Pharmacodynamic study showed that the in-situ gel injection extended the action time of metamizole relative to that when using the metamizole solution. Pharmacokinetic study revealed that the in-situ gel significantly increased the blood serum half-life and area under the curve), contributing to a sustained release and improved bioavailability. This study demonstrated that in-situ gel injection could prolong the action of metamizole in the body to reduce the number of administration times and has good clinical application.
摘要：
安乃近在体内容易分解，作用时间短，生物利用度低。因此，需要频繁注射以维持其血浆浓度.本研究旨在设计和开发一种基于泊洛沙姆407和188的原位凝胶，以评估其长效解热作用。最佳溶胶-凝胶转变温度为35.9°C至36.3°C的原位凝胶形成systep00m可以使用比例为21-23％（w/v）的P407和比例为2-4％（w/v）的P188的组合来形成。体外侵蚀试验表明，原位凝胶的侵蚀曲线和安乃近释放率在6h时都达到约90％，揭示了原位凝胶侵蚀与药物释放之间的良好线性关系。用透析管进行的体外释放测试表明，安乃近从原位凝胶中的释放明显慢于从安乃近溶液中的释放。大约85%的安乃近在7小时内释放在透析管中,暗示良好的缓释效果。药效学研究表明，相对于使用安乃近溶液时，原位凝胶注射延长了安乃近的作用时间。药代动力学研究表明，原位凝胶显着增加了血清半衰期和曲线下面积），有助于持续释放和提高生物利用度。本研究表明，原位凝胶注射可以延长安乃近在体内的作用，减少给药次数，具有良好的临床应用价值。
