Synthesis and Screening of Non-Migrating Plasticizers for Medical Devices

医疗器械用非迁移增塑剂的合成与筛选

• 批准号: 7761697
• 负责人: Andrew D. Bolig
• 金额: $ 13.28万
• 依托单位: SAN FRANCISCO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7761697
• 关键词: Animal Model; Animals; Architecture; Area; Basic Science; Biocompatible; Biocompatible Materials; Blood; Catalysis; Characteristics; Chemicals; Chemistry; Collaborations; Communities; Consultations; Crystallization; Data; Development; Devices; Education; Elements; Endocrine Disruptors; Endocrine disruption; Esters; Exhibits; Funding; Goals; Health; Health Hazards; Health Personnel; Healthcare; Human; Industry; Journals; Knowledge; Leadership; Libraries; Life; Literature; Medical; Medical Device; Mentors; Methodology; Methods; Mission; Molecular Weight; Operative Surgical Procedures; Patients; Pattern; Performance; Phase; Plasticizers; Plastics; Polyesters; Polyethylenes; Polymers; Population; Procedures; Process; Property; Public Health; Publications; Recruitment Activity; Reproductive Health; Research; Research Personnel; Resistance; Risk; Scientist; Screening procedure; Series; Societies; Source; Spectroscopy, Fourier Transform Infrared; Statutes and Laws; Structure; Students; System; Testing; Toxic effect; Toxicology; Toy; Transition Elements; Underrepresented Minority; United States National Institutes of Health; Variant; Weight; Work; base; burden of illness; cancer risk; career; career development; catalyst; copolymer; design; disability; experience; flexibility; hazard; human male; improved; instrumentation; interest; macromolecule; male; migration; monomer; phthalates; physical property; prevent; programs; public health relevance; reproductive; reproductive development; skills; small molecule; symposium

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.

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的，对许多医疗程序至关重要。它们通常含有高百分比的邻苯二甲酸酯，这些酯赋予弹性，但从塑料中大量迁移，使患者暴露于潜在的生殖危害。这些材料最近已被禁止用于玩具，FDA建议在敏感的医疗应用中取代它们，主要是因为担心对人类男性生殖发育的风险。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，其对人类的毒理学尚不清楚。用大分子（支化聚酯）已经获得了有希望的结果，尽管目前的候选物容易分解成小分子，这些小分子类似地浸出并使患者暴露于未知的风险，伴随着增塑剂效率的损失。 这些研究将研究一类具有侧酯官能团的共聚物，其将为敏感应用的PVC共混物提供必要的物理性能，但不会迁移，并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离散剪裁材料性能的结构/性能关系的明确确定。本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抗迁移性。具体目标是：1）合成一系列具有侧基酯官能团的共聚物，系统地改变用于PVC增塑的设计元素2）确定聚合物结构-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。 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。 这些研究有可能为所有人类都会接触的已知生殖毒性物质提供替代品，其中许多物质在医疗程序中的水平较高。 非迁移性增塑剂的开发将允许继续使用柔性塑料材料，而不会使患者暴露于生殖健康危害。