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

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，日本和中国之间进行了一项关于生物医学聚合物的溶出试验和安全性评价的国际科学项目，内容如下：1.制定溶出度试验的基本方案。与上海第二医科大学的薛淼教授进行信息交流。Zhang Cal-Xia教授拜访了东京医科齿科大学的Atsushige Sato教授，并起草了溶出度试验的基本通用方案。溶出度试验基本条件的研究中国研究员顾国祯博士应邀到东京医科齿科大学进行为期3个月的溶出度试验基本条件的研究。将一片（10 x 15 x 1.7 min）义齿用聚合丙烯酸树脂浸入溶解介质中。溶解的产物是 ...更多信息 通过高效液相色谱法（HPLC）分析。采用反相柱，水/乙腈移动的相，温度40 ℃，流速1 ml/min，检测波长235 nm处的UV吸光度和一点绝对校准法作为标准通用方案。试验材料的主要成分为甲基丙烯酸甲酯（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。将测试材料树脂热固化并浸入超纯水或甲醇中。水浸法未检测到化学物质，而甲醇浸法检测到MMA、BPO和未定义物质的峰。MMA的溶解在浸泡第7天消失，而BPO的溶解持续到浸泡第21天。在15天的浸泡过程中，每克热固化树脂的总溶解量为17.3 mg MMA和4 mg BPO，表明超过10%的单体被溶解.安全评价方法的国际标准化。对国际标准化组织（ISO TC 194）、国际牙科联合会（FDI 106）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、琼脂覆盖法和微孔滤膜法，日本采用琼脂覆盖法和蛋白定量法，<51>德国采用铬释放法、琼脂覆盖法、蛋白定量法和中和法。人们认识到，需要对试验细胞和标准毒性物质进行标准化。考虑到机构间和机构内的重现性，使用供试品浸提液和L-929细胞系的中性红试验被指定为标准化试验方法的主要候选方法。这一国际科学项目为生物医用材料测试方法的标准化提供了大量有价值的基础资料。少

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