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Trial of development of therapeutic using PPS modified penetrating efficacy into brain.

使用 PPS 改良脑部渗透功效的治疗剂开发试验。

基本信息

批准号：
17590882
负责人：
SHIRABE Susumu
金额：
$ 2.24万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

The aim of this study was a trial of of development of therapeutic using PPS modified penetrating efficacy into brain. So far, Pentosan polysalfate (PPS) has been recognized as most effective agent among known anti-prion agent. Therefor, we designed to fractionate PPS to get low-molecular weight PPS (LMW-PPS). The concept to purify LMW-PPS is to raise the efficacy of penetration of Blood Brain Barrier (BBB).We applied three methods to fractionate PPS. 1) acid hydrolyzation methods 2) gel filtration 3) limiting dilution by LMW-PPS we obtained was aprox. 50-60% of original compound in molecular weight in agerrage. (molecular weight of PPS:4,700 Kd) Using these methods, aproximately same size were obtained. These LMW-PPS fractions were aplied to cell line, which produce abnormal prion proten to see the anti-prion effects. Most effecteive fraction was used for anaima experiments to evaluate in vivo efficacy.RESULTS1) LMW-PPS were obtained by three different methods.2) These LMW-PPS fractions showed anti-prion effect at the concentration of 1μg/ml in prion-infected cell lines.3) By in vivo sutudy, only mice which were inoculated LMW-PPS intraventrilularly survived significantly longer than control. No significance was observed among the mice, which were injected intraperitonealy. This result indicated that the LMW-PPS could not be a candate for therapeutic agent.

本研究的目的是尝试开发使用 PPS 改良的脑部渗透功效的治疗方法。迄今为止，戊聚糖聚硫酸酯（PPS）已被公认为已知的抗朊病毒剂中最有效的药剂。因此，我们设计对PPS进行分馏以获得低分子量PPS（LMW-PPS）。纯化LMW-PPS的目的是为了提高血脑屏障(BBB)的穿透效率。我们采用了三种方法来分离PPS。 1）酸水解方法2）凝胶过滤3）LMW-PPS有限稀释我们得到的大约是。平均分子量为原化合物的50-60%。 (PPS的分子量：4,700Kd) 使用这些方法，获得大致相同的尺寸。将这些 LMW-PPS 级分应用于产生异常朊病毒蛋白的细胞系，以观察抗朊病毒效果。将最有效的级分用于动物实验以评估体内功效。结果1）通过三种不同的方法获得LMW-PPS。2）这些LMW-PPS级分在1μg/ml的浓度下在朊病毒感染的细胞系中显示出抗朊病毒作用。3）通过体内研究，只有脑室内接种LMW-PPS的小鼠存活明显长于对照。在腹膜内注射的小鼠中没有观察到显着性。这一结果表明LMW-PPS不能作为治疗剂的候选者。