Synthesis and Screening of Non-Migrating Plasticizers for Medical Devices

描述（由申请人提供）：软PVC塑料材料，特别是在血袋和手术管中发现，对许多医疗程序至关重要。它们通常含有高比例的邻苯二甲酸酯，具有灵活性，但会从塑料中大量迁移，使患者暴露于潜在的生殖危害中。这些材料最近已被禁止用于玩具中，FDA建议在敏感的医疗应用中替换它们，主要是出于对人类男性生殖发育风险的担忧。目前还没有找到足够的、安全的替代品。已经研究了几种替代品，但大多数是从散装塑料中迁移的小分子，其对人体的毒理学尚不清楚。大分子（支链聚酯）已经获得了有希望的结果，尽管目前的候选物质很容易分解成小分子，同样会浸出，并使患者面临未知的风险，伴随着增塑剂效率的丧失。这些研究将研究一类具有垂坠酯功能的共聚物，这种共聚物将为PVC共混物提供必要的物理性能，用于敏感应用，但不会迁移，而且不会降解为未知毒理学的低聚物和单体。过渡金属催化将允许材料性质的离散剪裁，以确定结构/性质关系。当前工作的长期目标是了解如何优化大分子结构和功能，以提供用于医疗应用的高性能生物相容性材料，从而避免与当前产品相关的风险。研究将确定聚合物的哪些结构特征在提供柔性共混物的同时赋予最大的迁移阻力。具体目标是：1)合成一系列具有垂链酯功能的共聚物，系统地改变PVC的增塑剂设计元素2)确定聚合物的结构-性能关系，以防止增塑剂从PVC迁移3)确定重量，支化和酯含量对增塑剂性能的影响。

DESCRIPTION (provided by applicant): Soft PVC plastic materials, found notably in blood bags and surgical tubing, are crucial to a number of medical procedures. They are typically formulated with a high percentage of phthalate esters which impart flexibility, but migrate extensively from the plastic, exposing the patient to potential reproductive hazards. These materials have recently been banned from toys, and the FDA has recommended that they be replaced in sensitive medical applications, largely due to concern over risks to reproductive development in human males. Adequate, safe replacements have not yet been identified. Several alternatives have been investigated, but most are small molecules which migrate from bulk plastics, and whose toxicology in humans is unknown. Promising results have been obtained with macromolecules (branched polyesters), though current candidates readily decompose to small molecules which similarly leach out and expose the patient to unknown risks, accompanied by loss of plasticizer efficiency. These studies will investigate a class of copolymers with pendant ester functionality which will provide requisite physical properties to PVC blends for sensitive applications, but which do not migrate, and further, do no degrade to oligomers and monomers of unknown toxicology. Transition metal catalysis will allow discrete tailoring of materials properties for definitive determination of structure/property relationships. The long-term objective of the present work is to understand how macromolecular architecture and functionality may be optimized to provide high-performance biocompatible materials for medical applications which avoid the risks associated with current products. Studies will determine which structural features of polymers impart maximal resistance to migration while providing flexible blends. The Specific Aims are: 1) Synthesize a series of copolymers with pendant ester functionality, with systematic variation of design elements for plasticization of PVC 2) Determine polymer structure-property relationships to prevent plasticizer migration from PVC 3) Determine effects of weight, branching, and ester content on plasticizer performance. PUBLIC HEALTH RELEVANCE: The impact of the proposed research on public health is considerable. These studies have the potential to provide replacements for substances of known reproductive toxicity to which all humans are exposed, many at elevated levels in medical procedures. The development of non-migrating plasticizers will allow the continued necessary use of flexible plastics materials without exposing patients to reproductive health hazards.