Japan-China international study on standardization of dissolution tests and safety evaluation of biomedical polymers

中日生物医用高分子溶出试验标准化及安全性评价国际研究

• 批准号: 03044166
• 负责人: SATO Atsushige
• 金额: --
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Overseas Scientific Survey.
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03044166/
• 关键词: Biomedical materials; Dissolution test; Acrylic resin denture; Unreacted monomer; Safety evaluation; Cytotoxicity test

The toxicity of biomedical polymers originates in the toxicity and solubility of chemicals dissolved from the polymers. Considering the importance of international balances, an international scientific project between Japan and China was conducted on the dissolution tests and safety evaluation of biomedical polymers on. the following items.1. Development of basic protocol for dissolution tests.Information exchanges were done with Prof. Xue Miao of Shanghai Second Medical University. Prof. Zhang Cal-Xia visited Prof. Atsushige Sato at Tokyo Medical and Dental University and made up a draft of the basic common protocol for dissolution tests.2. Study on the fundamentals for dissolution tests.A Chinese researcher, Dr. Gu Guozhen, was invited to Tokyo Medical and Dental University for 3 months engage in searching the basic condition for dissolution tests. A piece (10 x 15 x 1.7 min) of polymerized acrylic resin for denture use was immersed in dissolution medium. The dissolved products were … More analyzed by high performance liquid chromatography (HPLC). The reverse phase column, water/acetonitrile mobile phase, temperature at 40ﾟC, flow rate at 1 ml/min, UV absorbance at 235 nm for detection wave length and one-point absolute calibration method were adopted as the standard common protocol. The major components of test materials were methyl methacrylate (MMA), hydroquinone, ethylene glycol dimethacrylate, benzoyl peroxide (BPO), polymethyl methacrylate and cosmetics. The test material resin was heat-cured and immersed either in ultrapure water or in methanol. No chemicals were detected on water imme rsion, whereas peaks of MMA, BPO and undefined substances were obtained on methanol immersion. The dissolution of MMA disappeared on the 7th day of immersion, while that of BPO continued to the 21st day of immersion. The total amounts of dissolution from one gram of heat-cured resin during 15 days immersion were 17.3 mg of MMA and 4mg of BPO, indicating that more than 10% of monomer was dissolved.3. International standardization of safety evaluation method. The International Standardization Organization (ISO TC 194), the Federation Dentaire Internationals (FDI 106), and the cytotolfcity tests adopted in Germany, England, China and Japan were compared. The Cr release assay, agar overlay assay, and millipore filter assay were adopted in ISO/FDI the agar overlay assay and protein quantification assay were in Japan, and the ^<51>Cr-release assay, agar overlay assay, protein quantification assay and neutralized assay were adopted in Germany. It was recognized that the standardization for test cells and standard toxic substances is needed. Considering the inter-and intra-institutional reproducibility, the neutralred assay using test material extracts and L-929 cell line was nominated as the primary candidate for the standardized test method. This international scientific project offered a lot of basic valuable information for standardizing test method of biomedical materials. Less

生物医用聚合物的毒性来源于从聚合物中溶解的化学物质的毒性和溶解性。考虑到国际平衡的重要性，日本和中国就生物医用聚合物的溶出度试验和安全性评价进行了国际科学项目。下列事项：1.与上海第二医科大学薛淼教授进行了信息交流。张卡尔霞教授拜访了东京医科大学的佐藤敦教授，并起草了溶出度试验的基本通用方案草案。溶出度试验的基本条件研究：中国研究员顾国珍博士应邀到东京医科大学进行为期3个月的溶出度试验基本条件的研究。将一片(10×15×1.7分钟)聚合型义齿用丙烯酸树脂浸泡在溶解介质中。溶解产物为…更多的分析通过高效液相色谱(HPLC)进行。采用反相柱，水/乙腈流动相，温度40ﾟC，流速1ml/m in，检测波长2 35 nm，一点绝对校准法作为标准通用方法。测试材料的主要成分是甲基丙烯酸甲酯(MMA)、对苯二酚、二甲基丙烯酸乙二醇酯、过氧化苯甲酰(BPO)、聚甲基丙烯酸甲酯和化妆品。试验材料树脂经过热固化，浸泡在超纯水或甲醇中。在水溶液中未检测到化学物质，而在甲醇溶液中得到MMA、BPO和未知物的峰。MMA在浸泡7d时溶解消失，而BPO在浸泡21d时溶解消失。每克热固化树脂在浸泡15天内的总溶出量为17.3 mg甲基丙烯酸甲酯和4 mg过氧化苯甲酰，表明单体的溶出量超过10%。安全评价方法的国际标准化。对国际标准化组织(ISO TC194)、国际电工联合会(FDI106)以及德国、英国、中国和日本采用的细胞毒性试验进行了比较。ISO/FDI采用铬释放法、琼脂叠加法和微孔滤过法，日本采用琼脂叠加法和蛋白质定量法，德国采用铬释放法、琼脂叠加法、蛋白质定量法和中和法。人们认识到，试验室和标准有毒物质的标准化是必要的。考虑到机构间和机构内的重复性，采用试材提取物和L-929细胞株的中和试验被提名为标准化试验方法的主要候选者。这一国际科学计划为生物医学材料测试方法的标准化提供了许多基本的有价值的信息。较少

项目成果

Atsushige Sato: "Standardization of dissolution tests for dental materials" J. Stomatol Soc. Japan.59. (1992)

Atsushige Sato：“牙科材料溶出测试的标准化”J. Stomatol Soc。

Toshio Hongo: "Unreacted monomer and catalyst of acrylic resin dentures" J. Jap. Soc. Dental Materials and Devices. 11. (1992)

Toshio Hongo：“丙烯酸树脂假牙的未反应单体和催化剂” J. Jap.

佐藤 温重他: "歯科材料溶出試験の基準化" 口病誌. 59. (1992)

Atsushi Sato 等人：“牙科材料溶解测试的标准化”口腔医学杂志 59。（1992 年）

本郷 敏雄他: "アクリルレジン義歯床の残留モノマ-、重合触媒" 歯科材料・器械. 11. (1992)

Toshio Hongo 等人：“丙烯酸树脂义齿基托中的残留单体和聚合催化剂”《牙科材料和仪器》11。（1992 年）