The development of chemotherapoetic agents for periodontitis utilizing local drug delivery system.

本研究旨在利用局部给药系统建立新型牙周病化疗药物。司帕沙星（SPFX）对牙周致病菌有较好的上级抗菌活性，因此被选为该制剂的抗菌剂。在我们的初步研究中，我们检查了各种基质的控释活性。其中，基于共聚{乳酸/乙醇酸}的非水合凝胶显示出最好的特性。根据该结果，通过将2%SPFX与共聚{乳酸/乙醇酸}混合来制备测试试剂。评价该试验试剂持久性的体外实验表明，药物释放持续17天，直至完全消失，随后出现初始突释，释放速率逐渐降低。并考察了该试剂在牙周袋中SPFX释放的连续性。当应用非对照试剂时， ...更多信息 在MBC 90（最小杀菌浓度）下，袋在24小时内对临床分离的A. a.和P.G.与此相反，测试试剂在牙周袋中施用后甚至72小时仍保留浓度为4 mg/ml的SPFX，并且保持药物水平超过针对A.a.和P.G.这些结果表明，该测试试剂比以前开发的试剂在牙周袋中显示更长时间的有效药物浓度。然后评价该试剂局部应用于预处理牙周袋的临床效果。与单独施用非控释药物或基质的部位相比，施用控释药物的部位在施用后1周的测试部位的临床参数显著改善。然而，当没有进行进一步的牙周治疗时，测试部位的临床参数接近对照部位的值，并且最终在应用后12周，两个部位的值变得相似。龈下菌群植物群分析显示，龈下菌群阳性率和龈下菌群阳性率均下降。和螺旋体，以及P. g.应用后1周和4周的阳性部位。最后，研究了根培养与药物施用的联合效应。联合治疗组与单纯根管治疗组的临床特征及龈下微植物群无明显变化。结果表明，本研究所建立的新型牙周炎化疗药物具有较好的抗菌活性和较长的持效期，是一种具有局部给药系统特点的牙周炎化疗药物。少

This study was conducted to establish the new chemotherapeutic agents for periodontal diseases utilizing the local drug delivery system. Sparfloxacin (SPFX) 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 copoly{lactic/glycolic}acid showed the best characteristics for its purpose. According to this result, test reagent was prepared by mixing 2% SPFX with copoly {lactic/glycolic}acid. In vitro experiments to evaluate the persistence of this test reagent showed that the drug releasing lasted for 17 days until it was completely disappeared, following the initial burst and gradual decrease of releasing rate. The continuity of SPFX releasing in the periodontal pocket using this reagent was also examined. When the non-controlled reagent was applied, the SPFX concentration in … More the pockets was declined in 24 hours under MBC90(minimum bactericidal concentration) against clinically isolated A.a. and P.g.. In contrast, test reagont retained SPFX at the concentration of 4 mg/ml even 72 hours after application in the periodontal pocket and kept the drug level over MBC90 against A.a. and P.g.. These results suggested that this test reagent demonstrate the effective drug concentration in periodontal pocket for longer period than previously developed reagents. Then we evaluated the clinical effects of topical application of this reagent for pretreated periodontal pockets. The clinical parameters of the tested sites 1 week after the application, where the controlled release-drug was applied, was significantly improved in comparison with the sites where non-controlled release-drug or matrix alone was applied. However, when no further periodontal treatment was done, the clinical parameters of the tested sites got close to the value of the control sites and finally the value of both sites became similar 12 weeks after the application. On the other hand, the analysis of subgingival micro flora showed the decrease of both the positive rate of P.g. and Spirochete, and the frequency of P.g. positive sites at 1 and 4 weeks after the application. Finally, the combined effect of root plaining and drug application was studied. The clinical feature and the sub gingival micro flora did not show any significant change between the sites of combination therapy and root plaining alone. These data show that the new reagent established in this study demonstrates more effective antibacterial activity and longer persistence than any other known reagents and evaluated as one of the unique chemotherapeutic agents for periodontitis with the feature of local drug delivery system. Less