POLYMERS WITH BIOACTIVE DEGRADATION PRODUCTS

芳香族聚酸酐是临床上用于治疗脑癌的药物释放系统。然而，降解速度慢和降解产物相对不溶，特别是在有机溶剂中，是大多数生物医学应用的主要缺点。为了改善芳香族聚酸酐的降解性和溶解性，将芳香族梯级取代由对位取代改为邻位取代。正如预期的那样，邻位取代聚合物具有优异的溶解性能，并且似乎经历了表面侵蚀。我们对聚酸酐降解产物的评估导致了一种具有潜在重要应用前景的替代聚合物的设计。用酯键取代醚键可得到一种聚合物，可降解为水杨酸(SA)，水杨酸是一种抗炎、解热和止痛剂。建议的聚合物是可生物降解(可生物吸收)的材料，可用于短期牙科治疗。聚合物的降解产物(SA)可以减少牙周病手术后的炎症和疼痛。该系统是聚合物本身是控释系统的第一个例子：聚合物降解成具有抗炎和止痛特性的SA。这些聚合物可能会在减少术后疼痛和炎症方面得到应用，此外还可以在牙周病中创造一个反对细菌过程的环境。局部释放与口服SA不同，可以想见，它将减少手术后通常开出的水杨酸的全身不良反应。牙周病包括一组相关的微生物诱导的慢性炎症性疾病，这些疾病破坏支撑牙齿的组织。这些疾病可导致新的健康牙周结构的正常软硬组织的丧失，同时减轻牙周手术后的疼痛。此外，较低的pH值将不利于一些牙周病细菌。这项建议的总体目标是研究通过可降解的聚(酸酐-酯)(PAE)膜局部输送水杨酸将促进愈合过程的假说。

Aromatic polyahydrides are clinically used as drug delivery systems for treatment of brain cancer. However, the slow degradation rate and the relative insolubility of the degradation products, especially in organic solvents, are major drawbacks for most biomedical applications. To improve the degradability and solubility of the aromatic polyanhydrides, the aromatic rung substitution was altered from para- to ortho- substituted. As expected, the ortho-substituted polymers have excellent solubility properties and appear to undergo surface erosion. Our evaluation of the degradation products obtained from polyanhydrides led to the design of an alternative polymer with potentially significant applications. Replacing the ether bond with an ester bond yields a polymer that degrades into salicylic acid (SA), an anti-inflammatory, antipyretic and analgesic agent. The proposed polymers are biodegradable (bioresorbable) materials that can be used for short-term dental treatments. The polymer's degradation products (SA) can reduce post-operative inflammation and pain following surgery for periodontal diseases. This system is the first example in which the polymer itself is a controlled-release system: the polymer degrades into SA which has anti-inflammatory and analgesic properties. These polymers may find application in decreasing post-operative pain and inflammation, in addition to creating an environment averse to bacterial processes in periodontal disease. Localized release, unlike orally ingested SA, will conceivably reduce the systemic adverse affects of salicylic acid which is generally prescribed after surgery. Periodontal disease comprise a group of related microbial-induced chronic inflammatory disorders that destroy the tissue supporting the teeth. These diseases can result in loss of normal soft and hard tissue of new health periodontal architecture while reducing the post-operative pain after periodontal surgery. Additionally, lowered pH will be unfavorable to some periodontopathic bacteria. The overall objective of this proposal is to investigate the hypothesis that local delivery of salicylic acid via degradable poly(anhydride-esters) (PAE's) membranes will enhance the healing process.