BIOERODIBLE SYSTEM FOR TREATMENT OF PERIODONTAL DISEASE

这项研究的长期目标是开发一种可生物侵蚀的， 用于治疗牙周炎的软膏状聚合物。这 输送系统将能够通过一种 侵蚀控制过程，动力学接近零级，来自 在牙周口袋里。治疗剂(例如， 四环素)通过直接混合加入到聚(邻位酯)中 含有易水解性连接的软膏状聚合物。 药物的释放由扩散和混合控制 这些联系分裂的速度。因为聚(邻位酯)是 对酸敏感，可通过以下方法控制水解率 加入的酸性辅料。此外，水解率 随着聚合物亲水性的增加而增加。因此，这个比率 聚合物的水解和随后的药物释放可以相当精确地 控制住了。易于将感兴趣的治疗剂结合在一起， 无论是抗菌剂之类的小分子，还是 大分子，如多肽或蛋白质，提供了一种输送系统 它可以从牙周内输送一系列药物 口袋里。这项研究将开发这样一个系统，并对各个方面进行评估 它的释放和递送，有效性和毒性。曾经是一名工作人员 聚合物软膏已经开发出来，它的特点是 评价体外药物释放速率和能力的广泛研究 将候选软膏粘在潮湿的牙齿表面上。 致突变性、急性口服和静脉毒性以及口服亚慢性毒性 将进行毒性测试；粘膜刺激性和限制性 将使用带有斑块的比格犬进行疗效研究 牙周炎。在对比格犬的疗效研究中， 四环素聚合物软膏将由注射器运送至 牙周袋和临床疗效评估-包括 菌斑指数、牙龈指数、探查附着丧失和探查 口袋深度赢了。治疗后，龈沟液 样本将用过滤纸条(围纸)放置在 口袋的小孔。将对这些脑沟液样本进行评估 它们的四环素含量及其体外抗菌活性 选定的厌氧生物。

The long-term objective of this research is to develop a bioerodible, ointmentlike polymer for use in the treatment of periodontitis. This delivery system will be capable of releasing a therapeutic agent by an erosion-controlled process, with kinetics approaching zero order, from within the periodontal pocket. The therapeutic agent (for example, tetracycline) is incorporated by direct mixing into a poly (ortho ester) ointmentlike polymer that contains hydrolytically labile linkages. Release of the medicament is controlled by a combination of diffusion and the rate at which these linkages cleave. Because poly (ortho esters) are acid sensitive, the rate of hydrolysis can be controlled by means of incorporated acidic excipients. In addidon, the rate of hydrolysis increases as the hydrophilicity of the polymer increases. Thus, the rate of polymer hydrolysis and consequent drug release can be fairly precisely controlled. The easy incorporation of the therapeutic agent of interest, whether it is a small molecule such as an antibacterial agent or a macromolecule such as a peptide or protein, affords a delivery system that can deliver a range of medicaments from within the periodontal pocket. This study will develop such a system and evaluate all aspects of its release and delivery, efficacy, and toxicity. Once a working polymeric ointment has been developed, it will be characterized by extensive studies evaluating in vitro drug delivery rate and the ability of the candidate ointments to adhere to moist tooth surfaces. Mutagenicity, acute oral and intravenous toxicity, and oral subchronic toxicity testing will be performed; and mucosal irritancy and limited efficacy studies will be conducted using beagle dogs with plaque induced periodontitis. In the efficacy study in beagle dogs, the tetracycline-loaded polymeric ointment will be delivered by syringe to the periodontal pocket, and clinical efficacy assessments-including the plaque index, gingival index, probing loss of attachment, and probing pocket depth-win be made. Following treatment, gingival crevicular fluid saples will be collected with filter paper strips (Periopaper) placed at the pocket orifice. These crevicular fluid samples will be evaluated for their tetracycline content and in vitro antibacterial activity against selected anaerobic organisms.