本文選題：替硝唑　切入點：緩釋栓劑　出處：《毒理學雜志》2017年01期 　論文類型：期刊論文

【摘要】：目的比較研究替硝唑長效緩釋栓劑、陰道凝膠劑和陰道緩釋片3種劑型的釋放度、釋放機制及特殊毒性。研究三者的溶出曲線、釋藥機制及緩釋效果。方法將自制片劑、自制凝膠劑和市售栓劑分別做體外溶出試驗,繪制相應的溶出曲線,研究釋放機制。皮膚過敏性試驗:取豚鼠12只,隨機分成4組,分別涂抹3種劑型藥物及陽性對照藥,重復給藥誘導,觀察有無過敏反應。家兔陰道刺激性試驗:取雌兔12只,隨機分為4組,其中3組為給藥組,1組為空白對照組。將藥物推入大耳白兔陰道5cm,觀察現象。隔天給藥1次,連續(xù)7次,觀察動物情況。隨后處死動物,摘取生殖器官,對其進行刺激性性評價,做成切片進行病理學檢查。結果栓劑符合Higuchi方程,為擴散與溶脹雙重機制,且以擴散為主;凝膠劑符合Higuchi方程,為擴散與骨架溶蝕雙重機制,且以擴散為主;片劑符合零級釋藥模型,為擴散與骨架溶蝕雙重機制,且以骨架溶蝕為主。片劑零級釋放,釋放更均勻。結論釋藥效果比較研究發(fā)現,緩釋效果片劑優(yōu)于其他二者,緩釋片劑的釋放更均勻。刺激性過敏性試驗結果表明3種劑型均無刺激致敏性,安全可靠。
[Abstract]:Objective to compare the release rate, release mechanism and special toxicity of tinidazole long-acting sustained-release suppository, vaginal gel and vaginal sustained-release tablet. Self-made gel and commercial suppository were used for dissolution test in vitro, corresponding dissolution curve was drawn, and release mechanism was studied. Skin anaphylactic test: 12 guinea pigs were randomly divided into 4 groups, 3 dosage forms and 3 positive control drugs were smeared respectively. The vaginal irritation test: 12 female rabbits were randomly divided into 4 groups. Three of them were treated as blank control group. The drug was pushed into the vagina of rabbits with big ears for 5 cm to observe the phenomenon. Once every other day, 7 times in succession, the animals were observed. Then the animals were killed and their reproductive organs were removed. The results showed that the suppository accords with Higuchi equation, which is the double mechanism of diffusion and swelling, and is mainly diffusive, and the gel conforms to Higuchi equation, which is the double mechanism of diffusion and skeleton dissolution. The tablets accord with the zero-order drug release model, which is the dual mechanism of diffusion and skeleton dissolution, and the skeleton dissolution is the main mechanism. The release of sustained-release tablets was more uniform than that of other two tablets. The results of irritation allergic test showed that all the three formulations had no irritation sensitization and were safe and reliable.
【作者單位】： 遼寧大學藥學院;遼寧省生物大分子計算模擬與信息處理工程技術研究中心;
【基金】：遼寧省教育廳高等學校創(chuàng)新團隊項目(項目編號:LT2015011)
【分類號】：R965
，

本文編號：1616522