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Development of Slow Releasing Anticancer Drug Based with Absorbable Biomaterial Chit*

基于可吸收生物材料 Chit 的缓释抗癌药物的开发*

基本信息

批准号：
04807093
负责人：
MATSUURA Hiroshi
金额：
$ 1.28万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

We studied the slow releasing property and anticancer, effect of Plachitin, which is reconstituted by combination of CDDP and chitin. This study deals in more detail with the slow releasing property, and the renal complications and the effectiveness for solid tumor were examined in mice and rabbits.1. After implantation of Plachitin (cotton type) in the abdominal wall of mice, the platinum concentration in the different organs was measured. In the abudominal muscle around the implanted Plachitin, a high concentration of platinum was maintained until 8 weeks and the the peak was 4 weeks after implantation. At the same time, the serum concentration of platinum remained low. In the kidney, the platinum concentration resembled the levels in the abdominal muscle, but no renal dysfunction was found serologically or historogically.2. When Plachitin was implanted around the solid tumor, the survival rates were improved and the gain in tumor weight was suppressed as compared with the controls. … More From these findings, Plachitin seemed to be effective as a slow releasing anticancer drug for topical application.3. We studied about intraarterial chemoembolization therapy by use of Plachitin too. One gram of Plachitin contained 300mg CDDP and the form of Plachitin was modified into particles (about 50um in diameter). VX2 tumor was inoculated in hind limb of rabbits. When VX2 tumor was grown 2cm in diameter, Plachitin was injected in the femoral artery. The study was carried out in four groups : Plachitin, CDDP, chitin, and control groups. The tumor growth ratio was significantly lower in Plachitin group compared with other groups (p<0.05). Tumor regression was noticed in Plachitin group only. The tumor Platinum (Pt) level was higher than serum and kidney Pt.level. Blood urea nitrogen and Ceratinine level were normal range in Plachitin group. From the above results it can be concluded that Plachitin particles released CDDP slowly around the tumor and the tumor growth was suppressed by the additive effect of CDDP and embolization. Renal toxicity of Plachitin was not recognized. Plachitin could be considered as an useful agent for chemoembolization therapy for the cancer patients. Less

本文研究了顺铂与甲壳素复合后的普拉希丁的缓释性能和抗癌作用。本研究以小鼠和家兔为实验动物，考察了其缓释性能、肾脏并发症及对实体瘤的疗效.将Plachitin（棉型）植入小鼠腹壁后，测量不同器官中的铂浓度。在植入Plachitin周围的子宫肌肉中，铂的高浓度维持至8周，并在植入后4周达到峰值。同时，铂的血清浓度保持较低。在肾脏中，铂浓度与腹部肌肉中的水平相似，但血清学或历史学上未发现肾功能障碍。当Plachitin植入实体瘤周围时，与对照组相比，存活率提高，肿瘤重量的增加受到抑制。 ...更多信息从这些发现来看，Plachitin似乎是一种有效的局部应用的缓释抗癌药物。我们还研究了Plachitin在动脉化疗栓塞治疗中的应用。每克Plachitin含有300mg CDDP，并且Plachitin的形式被修饰成颗粒（直径约50 μ m）。将VX2肿瘤接种于兔后肢。当VX2肿瘤生长至直径2cm时，股动脉注射Plachitin。实验分四组进行：Plachitin组、CDDP组、几丁质组和对照组。Plachitin组肿瘤生长率明显低于其他各组（p<0.05）。仅在Plachitin组中观察到肿瘤消退。肿瘤铂（Pt）水平高于血清和肾脏铂水平。Plachitin组血尿素氮、血清肌酐水平均在正常范围内。从以上结果可以得出结论，Plachitin颗粒在肿瘤周围缓慢释放CDDP，并且通过CDDP和栓塞的叠加效应抑制肿瘤生长。未发现Plachitin的肾毒性。Plachitin可作为肿瘤化疗栓塞治疗的有效药物。少