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治疗牙周病的新型化疗药物。司帕沙星(SPFX)对牙周病细菌具有良好的抗菌活性，因此被选为该新药的抗菌剂。在我们的初步研究中，我们考察了各种骨架的控释活性。其中，基于共聚乳酸/乙醇酸的非水凝胶表现出最好的特性。根据这一结果，将2%SPFX与共聚乳酸/乙醇酸混合制成试剂盒。体外药物释放试验表明，药物释放持续时间为17d，直至完全消失，随后药物释放速率开始爆发并逐渐下降。同时考察了SPFX在牙周袋中释放的连续性。当使用非受控试剂时，…中的磺胺嘧啶浓度对于临床分离的A.A.，更多的口袋在24小时内低于MBC90(最低杀菌浓度)。和P.G.相反，试验试剂在牙周袋中应用后72小时仍保留4 mg/ml的SPFX浓度，并使药物浓度保持在MBC90以上。和P.G.这些结果表明，该试剂在牙周袋中的有效药物浓度比以前研制的试剂要长。然后，我们评估了该试剂局部应用于牙周袋的临床效果。应用控释药物1周后，受试部位的临床参数较单纯使用非控释药物或基质的部位有显著改善。然而，当不再进行牙周治疗时，试验部位的临床参数接近对照部位的值，12周后两个部位的值变得相似。另一方面，龈下菌群分析显示，两种细菌的阳性率均下降。和螺旋体，以及P.G.涂药后1周和4周的阳性部位。最后，研究了平根与施药的联合效应。联合治疗与单纯根管治疗的临床特征和龈下微生物区系均无明显变化。这些数据表明，本研究建立的新试剂比已知的其他试剂具有更有效的抗菌活性和更长的持久性，是具有局部给药系统特点的独特的牙周炎化疗药物之一。较少

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