POLYMERS WITH BIOACTIVE DEGRADATION PRODUCTS

具有生物活性降解产物的聚合物

• 批准号: 6176012
• 负责人: KATHRYN Elizabeth UHRICH
• 金额: $ 3.76万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6176012
• 关键词: bioengineering /biomedical engineering; biomaterial development /preparation; biomaterial evaluation; biomaterials; biotransformation; calorimetry; drug delivery systems; fluorescence spectrometry; histology; implant; inflammation; infrared spectrometry; laboratory mouse; medical implant science; nuclear magnetic resonance spectroscopy; pathologic bone resorption; periodontium disorder; polymers; postoperative state; salicylate; wound healing

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.

芳香族聚芳醚在临床上用作治疗脑癌的药物递送系统。然而，缓慢的降解速率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。为了改善芳香族聚酸酐的降解性和溶解性，将芳香环取代基从帕拉改变为邻位取代。正如预期的那样，邻位取代的聚合物具有优异的溶解性，并且似乎经历表面侵蚀。我们的评估从聚酸酐得到的降解产物导致设计的替代聚合物具有潜在的重要应用。用酯键取代醚键产生降解成水杨酸（SA）的聚合物，水杨酸是一种抗炎、解热和镇痛剂。拟议的聚合物是可生物降解（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。这些聚合物可以用于减少术后疼痛和炎症，除了创造一个环境，避免牙周病的细菌过程。局部释放，不像口服摄入SA，可以想象的是，将减少水杨酸的全身不良反应，这通常是在手术后处方。牙周病包括一组相关的微生物引起的慢性炎症性疾病，这些疾病破坏了支撑牙齿的组织。这些疾病可以导致新的健康牙周结构的正常软组织和硬组织的损失，同时减少牙周手术后的术后疼痛。此外，降低的pH将不利于某些牙周病细菌。本提案的总体目标是研究通过可降解聚（丙二醇酯）（PAE）膜局部递送水杨酸将增强愈合过程的假设。