Synthesis and Screening of Non-Migrating Plasticizers for Medical Devices

描述(申请人提供)：柔软的聚氯乙烯塑料材料，特别是在血袋和外科管子中发现的，是一些医疗程序的关键。它们通常含有高比例的邻苯二甲酸酯，具有弹性，但从塑料中大量迁移，使患者暴露在潜在的生殖危险中。这些材料最近被禁止在玩具中使用，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。目前还没有确定足够、安全的替代方案。已经研究了几种替代品，但大多数是从散装塑料中迁移出来的小分子，其对人体的毒理尚不清楚。大分子(支化聚酯)已经取得了令人振奋的结果，尽管目前的候选分子很容易分解成小分子，类似地渗出，使患者暴露在未知的风险中，并伴随着塑化剂效率的丧失。这些研究将探索一类具有侧酯功能的共聚物，它将为敏感应用的PVC共混物提供必要的物理性能，但不会迁移，而且不会降解为毒理未知的齐聚物和单体。过渡金属催化将允许材料性能的离散剪裁，从而最终确定结构/性能关系。本工作的长期目标是了解如何优化大分子结构和功能，为医疗应用提供高性能的生物兼容材料，从而避免与现有产品相关的风险。研究将确定聚合物的哪些结构特征在提供灵活的混合物的同时提供最大的抗迁移能力。其具体目标是：1)合成一系列具有侧酯功能的共聚物，并系统地改变聚氯乙烯的增塑设计元素；2)确定聚合物的结构-性能关系，以防止增塑剂从聚氯乙烯中迁移；3)确定重量、支化和酯含量对增塑剂性能的影响。 公共卫生相关性：拟议的研究对公共卫生的影响是相当大的。这些研究有可能提供已知的生殖毒性物质的替代品，所有人类都会暴露在这些物质中，其中许多物质在医疗程序中处于较高水平。非迁移性增塑剂的开发将允许继续必要地使用柔性塑料材料，而不会使患者面临生殖健康危害。

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.