The development of controlled release-drug utilizing new quinolones for perlodontitis

本研究旨在利用局部给药系统开发新的牙周病化疗药物。选择托氟沙星（TFLX）作为抗菌药物，因为它对牙周病细菌具有良好的抗菌活性。我们在初步研究中考察了各种基质的控释活性。其中，以硫酸铝钾和HPMC2208为基材的非水合凝胶性能最好。根据该结果，将4% TFLX与硫酸铝钾和HPMC2208为基础的凝胶混合，制备了测试试剂。用试验试剂检测了TFLX在牙周袋内释放的持久性。结果表明，试验试剂在牙周袋内应用48小时后仍能保持10/γg/ml的TFLX浓度。该试剂用于牙周袋的安全性也得到了证实，因为该试剂用于牙周袋时没有出现医学和牙科状况的副作用。然后，我们评估了该试剂局部应用于预处理牙周袋的临床效果。应用控释药物2周后，与不治疗或单独应用基质的部位相比，应用控释药物的测试部位的临床参数没有明显改善。然而，本研究开发的牙龈卟啉单胞菌（Pg）的高灵敏度检测方法显示，在使用测试试剂2周后，与其他部位相比，使用测试试剂的部位Pg的比例有降低的趋势。这些数据表明，本研究开发的新试剂有可能成为具有局部给药系统特点的独特的牙周炎化疗药物之一。

This study was conducted to develop the new chemotherapeutic agents for periodontal diseases utilizing the local drug delivery system. Tosfloxacin (TFLX) was selected as anti-bacterial agent for this new agent because of its superior anti-bacterial activity against periodontopathic bacteria. We examined the controlled release activity of various matrices in our preliminary studies. Among them, non-hydrated gel based on potassium aluminum sulfate and HPMC2208 showed the best characteristics for its purpose. According to this result, test reagent was prepared by mixing 4% TFLX with gel based on potassium aluminum sulfate and HPMC2208. The persistence of TFLX releasing in the periodontal pockets using test reagent was also examined. In result, test reagent retained TFLX at the concentration of 10/γg/ml even 48 hours after application in the periodontal pocket. The safety of this reagent in application to periodontal pockets was also confirmed, because the side effects in medical and dental condition did not appear when this reagent was applied to periodontal pockets. Then, we evaluated the clinical effects of topical application of this reagent for pretreated periodontal pockets. The clinical parameters of the tested sites 2 weeks after the application, where the controlled release-drug was applied, was not significantly improved in comparison with the sites where non-treatment or matrix alone was applied. However, the high sensitive detectable method of Porphyromonas gingivalis (Pg) developed in this study showed that a tendency to decrease the proportion of Pg in the sites applied the test reagent in comparison with the other sites at 2 weeks after the application. These data show that the new reagent developed in this study has the possibility of becoming one of the unique chemotherapeutic agents for periodontitis with the feature of local drug delivery system.