POLYMERS WITH BIOACTIVE DEGRADATION PRODUCTS

芳香族多羟基化合物在临床上被用作治疗脑癌的药物传递系统。然而，缓慢的降解速度和降解产物的相对不溶性，特别是在有机溶剂中，是大多数生物医学应用的主要缺点。为了提高芳香族聚酸酐的可降解性和溶解度，将芳香族环取代由对取代改为邻取代。正如预期的那样，邻位取代聚合物具有优异的溶解度，并且似乎会受到表面侵蚀。我们对从聚酸酐中获得的降解产物的评估导致了一种具有潜在重要应用的替代聚合物的设计。用酯键取代醚键产生一种聚合物，该聚合物可降解为水杨酸（SA），一种抗炎、解热和镇痛剂。所提出的聚合物是生物可降解（生物可吸收）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一个控释系统的第一个例子：聚合物降解成具有抗炎和镇痛特性的SA。除了在牙周病中创造一个不利于细菌过程的环境外，这些聚合物还可用于减少术后疼痛和炎症。局部释放，不像口服SA，可以想象减少全身副作用的水杨酸，通常是在手术后开处方。牙周病包括一组相关的微生物引起的慢性炎症性疾病，这些疾病会破坏支撑牙齿的组织。这些疾病可导致牙周结构的正常软硬组织的丧失，同时减少牙周手术后的术后疼痛。此外，较低的pH值对某些牙周病细菌不利。本提案的总体目标是研究通过可降解的聚酸酐酯（PAE）膜局部递送水杨酸将促进愈合过程的假设。

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.