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

本研究的目的是利用PPS改良的穿透性脑治疗的开发试验。聚戊聚糖（PPS）是目前已知的抗朊病毒药物中最有效的一种。因此，我们设计了对PPS进行分馏得到低分子量PPS （LMW-PPS）。纯化LMW-PPS的目的是提高其穿透血脑屏障（BBB）的功效。我们采用了三种方法来分离PPS。1)酸水解法；2)凝胶过滤法；3)LMW-PPS极限稀释法。平均分子量为原化合物的50-60%。（PPS分子量：4700 Kd）使用这些方法，得到了大致相同的尺寸。将这些LMW-PPS组分应用于产生异常朊蛋白的细胞系，观察其抗朊病毒作用。采用最有效部位进行动物实验，评价其体内疗效。结果1)通过三种不同的方法获得LMW-PPS。2) LMW-PPS提取物在浓度为1μg/ml时对朊病毒感染细胞株具有抗朊病毒作用。3)通过体内实验，只有经脑室内接种LMW-PPS的小鼠存活时间明显长于对照组。腹腔注射小鼠间无显著性差异。这表明LMW-PPS不能作为治疗药物的候选。

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.