Novel Methacrylate-Thiol-Ene Composites for Dental Restorative Materials

用于牙科修复材料的新型甲基丙烯酸酯-硫醇-烯复合材料

• 批准号: 8780413
• 负责人: NEIL B CRAMER
• 金额: $ 15万
• 依托单位: COLORADO PHOTOPOLYMER SOLUTIONS, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8780413
• 关键词: Acrylates; Adhesions; Adhesives; Area; Biocompatible Materials; Clinical; Collaborations; Colorado; Composite Resins; Conversion disorder; Coupled; Coupling; Dental; Dental Materials; Development; Drug Formulations; Elements; Failure; Fatigue; Filler; Funding; Glass; Goals; Grant; Growth; Health; Individual; Knowledge; Lead; Legal patent; Licensing; Life; Longevity; Mechanical Stress; Mechanics; Methacrylates; Methodology; Nature; Optics; Orthodontic; Oxygen; Peer Review; Performance; Phase; Plant Resins; Polymers; Positioning Attribute; Prevalence; Procedures; Property; Publications; Qualifying; Reaction; Refractive Indices; Reliance; Resistance; Safety; Sampling; Services; Small Business Innovation Research Grant; Smiling; Solutions; Speed; Stress; Sulfhydryl Compounds; System; Technology; Testing; Time; Tooth structure; Toxic effect; United States National Institutes of Health; Universities; Urethane; Water; Work; base; biomaterial compatibility; bisphenol A; commercialization; composite restoration; design; experience; forging; improved; innovation; mechanical behavior; medical specialties; monomer; novel; polymerization; premature; restoration; restorative dentistry; restorative material; restorative resins; triethylene glycol dimethacrylate; uptake

DESCRIPTION (provided by applicant): Novel Methacrylate-Thiol-Ene Composites for Dental Restorative Materials. As the demand for aesthetically pleasing restorative materials has increased, so has the desire and demand for improved performance. Despite their increasing prevalence, the resin phase of these materials has remained largely unaltered since Bowen first proposed the materials nearly 50 years ago. Presently, composites suffer from shrinkage and stress that arise during polymerization, a subsequent lack of appropriate mechanical properties of the resin material, and low depth of cure for polymerization. The composites also contain in their core monomer the substitutent bisphenol-A, which is associated with ever increasingly significant regulatory and health concerns. Following polymerization, the composites also contain significant fractions of unreacted monomer that results in the critical presence of extractables that coupled with moisture uptake by the sample can lead to degradation. The result is often secondary cavities and premature failure where composites average lifetime is less than 8 years. Classically, the limitations of these materials have involved a trade-off between the mechanical behavior, the stress and the extent of reaction/conversion of the material that limits extractables and water sorption. The BisGMA/TEGDMA system has proven to be a local optimum within this overall flawed compromise. Here, we propose a novel methodology that changes the reaction paradigm and allows for improvement in each of these critical areas - lower shrinkage and stress, improved mechanics, higher extent of reaction, improved depth of cure along with the elimination of bisphenol-A, and reduced extractables and degradation. An approach using thiol-ene click reactions and monomers is combined with an improved methacrylate approach to yield dramatic improvements in each of these critical areas. Within the two aims of this work, two distinct elements of the formulation are targeted - development and optimization of the resin phase, and development and optimization of the filler/filler coupling agent combination. While both of these aims can proceed independently and will yield valuable results in and of themselves. The synergistic combination of these approaches will forge an entirely new composite dental restorative with expected improvements in conversion, reduced degradation and improved biocompatibility and public safety, mechanics and service life. Specifically, in the first aim, we seek to incorporate urethane-based methacrylates in place of bisphenol-A based monomers. The increased refractive index of the thiol-ene components enables the use of non-bisphenol-A-based monomers - with corresponding benefits of enhanced material properties. Thus, the increased urethane content will result in both improved material properties and reduced shrinkage stress as compared to utilizing BisGMA or BisEMA as the methacrylate in methacrylate-thiol-ene formulations. Second, we propose to focus on the comprehensive development of an integrated filler system that is improved overall and designed specifically for integration with the methacrylate-thiol- ene resins. Our preliminary results have demonstrated a much greater mechanical property enhancement in composite methacrylate-thiol-ene systems than in the control composite BisGMA/TEGDMA systems. These results indicate that the increased conversion of methacrylate-thiol-ene systems will not only dramatically reduce the amount of extractable monomer but also enhance the interaction between the resin phase and the fillers, leading to enhanced mechanical properties. This same benefit is expected to lead to improved adhesion with the native tooth structure. The proposed aims are predicated on the hypothesis that appropriate materials synthesis and subsequent incorporation of urethane-methacrylate base components, optimization of the formulation composition and polymerization mechanism, and optimally designed and modified fillers will improve dental composites through dramatic reductions in shrinkage stress, improvement in composite mechanical properties, moisture uptake and reduced extractables along with improved toxicity and implementation of BPA-free formulations. Results to date demonstrate improved polymerization rates, volume shrinkage induced stress, mechanical properties, depth of cure, oxygen inhibition, toxicity and final conversion. These results will for dental composite systems with enhanced longevity and improved clinical scope. The methacrylate-thiol-ene technology was developed at the University of Colorado by Drs. Cramer and Bowman with funding from an NIH R01 grant (DE018233 - Development of Novel Thiol-Ene-Methacrylate Composites for Dental Restorative Materials). In total, the prior work supported in this area by the R01 grant, of which the PI for this proposal was a co-PI, resulted in 17 peer reviewed publications and two US patents that have been optioned by Colorado Photopolymer Solutions (CPS). Drs Cramer and Bowman have previous experience developing and commercializing dental restorative materials through their collaboration with Septodont Confi-Dental products. During this collaboration, a novel methacrylate formulation from University of Colorado was licensed by Septodont Confi-Dental Products Division and is available commercially as N'Durance (http://www.septodontusa.com/products/n-durance). This provides us with first-hand knowledge for the testing and procedures necessary to commercialize a dental restorative material as well as a potential partner for Phase III. CPS has significant experience in both dental materials and (meth)acrylate and thiol-ene materials. CPS has recently developed and licensed two orthodontic adhesives (Perfect-A-Smile and Bond Aligner) that are currently commercially available through Reliance Orthodontic Products (www.relianceorthodontics.com). CPS also develops and manufactures a range of (meth)acrylate and thiol-ene based formulations for adhesives, optical materials, and other specialty applications.

描述（由申请人提供）：用于牙科修复材料的新型甲基丙烯酸硫醇 - 荷兰烯复合材料。随着对美学上令人愉悦的恢复材料的需求增加，对性能的渴望和需求也增加了。尽管出现了越来越多的患病率，但这些材料的树脂阶段自鲍恩（Bowen）近50年前首次提出材料以来，这些材料的树脂阶段在很大程度上都没有改变。目前，复合材料会遭受聚合过程中产生的收缩和压力，随后缺乏树脂材料的适当的机械性能以及低固化深度以进行聚合。这些复合材料还包含替代双酚-A的核心单体，这与日益显着的调节和健康问题有关。聚合后，复合材料还含有未反应的单体的显着部分，这会导致萃取物的临界存在与样品的水分吸收相结合会导致降解。结果通常是次生空腔和早产材料的平均寿命小于8年。从经典上讲，这些材料的局限性涉及机械行为，应力和反应/转化程度之间的权衡，从而限制了可提取物和吸附的材料的反应/转化程度。事实证明，BISGMA/TEGDMA系统在这一整体缺陷妥协中是局部最佳。在这里，我们提出了一种新的方法，该方法可以改变反应范式，并可以改善这些关键区域 - 较低的收缩和压力，改善的力学，较高的反应程度，改善的治疗深度以及消除双酚-A，以及减少的提取物和降解。使用硫醇 - 烯键反应和单体的方法与改进的甲基丙烯酸酯方法相结合，以在这些关键领域中的每个关键区域产生显着改善。在这项工作的两个目标中，公式的两个不同元素是针对的 - 树脂阶段的开发和优化，以及填充/填充偶联剂组合的开发和优化。尽管这两个目标都可以独立进行，并将在本身中产生宝贵的结果。这些方法的协同组合将制造一种全新的复合牙齿修复，并预期改善转化，降解减少以及改善的生物相容性以及公共安全，机械和服务寿命。具体而言，在第一个目的中，我们试图将基于尿烷基的甲基丙烯酸酯代替基于双酚A的单体。硫醇 - 烯成分的折射率增加，可以使用非基于A的单体 - 具有相应的增强材料特性的好处。因此，与利用甲基丙烯酸硫醇 - 硫醇配方中的甲基丙烯酸甲酯相比，增加的氨基烷含量将导致改善的材料特性和减少的收缩应激。其次，我们建议专注于整体上改进的集成填充系统的综合开发，并专门设计用于与甲基丙烯酸硫醇 - 硫醇树脂的集成。 我们的初步结果表明，复合甲基丙烯酸 - 硫醇烯系统的机械性能增强要大得多，而对照复合Bisgma/TeGDMA系统中的机械性能则更大。这些结果表明，甲基丙烯酸硫醇 - 烯系统系统的转化率不仅会大大减少可提取单体的量，而且还可以增强树脂相和填充剂之间的相互作用，从而增强机械性能。预计同样的好处将改善与天然牙齿结构的粘附。 The proposed aims are predicated on the hypothesis that appropriate materials synthesis and subsequent incorporation of urethane-methacrylate base components, optimization of the formulation composition and polymerization mechanism, and optimally designed and modified fillers will improve dental composites through dramatic reductions in shrinkage stress, improvement in composite mechanical properties, moisture uptake and reduced extractables along with improved toxicity and implementation of无BPA配方。迄今为止的结果表明，聚合速率提高，体积收缩诱导的应力，机械性能，治疗深度，氧抑制，毒性和最终转化率。这些结果将使牙科复合系统具有增强的寿命和改善的临床范围。 Drs在科罗拉多大学开发了甲基丙烯酸酯 - 硫醇 - 烯技术。 Cramer和Bowman获得了NIH R01赠款的资金（DE018233-开发用于牙科修复材料的新型硫醇 - 烯甲基丙烯酸酯复合材料）。总的来说，R01赠款在该领域支持的先前工作，该提案的PI是Co-Pi，导致 17同行审查的出版物和两项由科罗拉多州光聚合物解决方案（CPS）选择的美国专利。 Cramer博士和Bowman先前通过与Septodont Conci-Dental Products的合作来开发和商业化牙科修复材料的经验。在这项合作期间，科罗拉多大学的一种新型的甲基丙烯酸酯配方获得了Septodont Conci-Dental Products部门的许可，并以N'Durance（http://www.septodontusa.com/products/n-durance）在商业上购买。这为我们提供了有关将牙科修复材料商业化的测试和程序以及第三阶段的潜在合作伙伴进行商业化的第一手知识。 CPS在牙科材料和（甲基丙烯酸酯和硫醇烯材料）方面都有丰富的经验。 CPS最近已开发并许可了两种正畸胶粘剂（Perfect-A-Smile and Bond Aligner），这些粘合剂目前可通过Reliance Orthodtontic产品（www.relianceorthordictics.com）商业获得。 CP还开发并制造了一系列（甲基丙烯酸酯和硫醇烯基的配方），用于粘合剂，光学材料和其他专业应用。