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Development of efficient production of antitumor agents originated from plant and their application to antitumor therapy using hybrid liposomes

植物源抗肿瘤药物高效生产的开发及其在混合脂质体抗肿瘤治疗中的应用

基本信息

批准号：
14350440
负责人：
FURUSAKI Shintaro
金额：
$ 9.41万
依托单位：
Sojo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Culture conditions for the effective production of antitumor agents such as Paclitaxel (Taxol) and improvement of callus growth in the callus culture were examined (refer to 1-3 below). To enhance the inhibitory effect of Taxol on the growth of tumor cells, hybrid liposomes including biological materials and Taxol were prepared and their growth inhibitory effects were also examined (refer to 4 below). The results obtained are as follows.1. Appropriate organic solvents, which solubilized Taxol easily, were selected from a variety of organic solvents to recover Taxol from the aqueous medium due to hydrophobic interaction. Aliphatic hydrocarbons having log P values of more than 5, fatty alcohols and triglycerides were good candidates for the enhancement of Taxol production and improvement of the callus growth. An elicitor solubilized in selected organic solvents was effective for the Taxol production and the callus growth.2. Foam, which has an apparently hydrophobic property, was used for the recovery of Taxol from the medium instead of the organic solvents. Selective accumulation of Taxol in the foam was observed in the callus culture, which indicated that foam had an excellent candidate for selective recovery of Taxol.3. Generally, stirred or bubble column bioreactor was utilized for the large scale callus culture. The effect of shaking speeds on the callus growth and Taxol production was examined. Optimum shaking speed for maintaining callus growth and Taxol production was examined.4. Biological materials were used to increase the solubility of Taxol in water. Hybrid liposomes including biological materials and Taxol simultaneously formed appropriate size of liposomes and were stable for several weeks. Besides, the hybrid liposomes showed an inhibitory effect on the growth of the tumor cells. The data suggest that the hybrid liposomes could be a novel chemotherapeutic agent in the treatment of cancers.

检查了有效生产抗癌剂如紫杉醇（Taxol）和改善愈伤组织培养物中愈伤组织生长的培养条件（参见下文1-3）。为了增强紫杉醇对肿瘤细胞生长的抑制作用，制备了包括生物材料和紫杉醇的混合脂质体，并检测了它们的生长抑制作用（参见下面的4）。研究结果如下：1.从多种有机溶剂中筛选出适合于紫杉醇增溶的有机溶剂，利用疏水作用从水溶液中回收紫杉醇。脂肪烃的log P值大于5，脂肪醇和甘油三酯是很好的候选人，为增强紫杉醇的生产和改善的愈伤组织生长。在选定的有机溶剂中增溶的诱导子对紫杉醇的产生和愈伤组织的生长是有效的.泡沫具有明显的疏水性，用于从介质中回收紫杉醇，而不是有机溶剂。在愈伤组织培养中，紫杉醇在泡沫中的选择性积累，表明泡沫是紫杉醇选择性回收的良好候选材料.大规模愈伤组织培养通常采用搅拌或鼓泡塔生物反应器。研究了振荡速度对愈伤组织生长和紫杉醇产量的影响。研究了维持愈伤组织生长和紫杉醇产量的最佳振荡速度.采用生物材料提高紫杉醇在水中的溶解度。生物材料和紫杉醇的混合脂质体同时形成适当大小的脂质体，并稳定数周。此外，杂化脂质体对肿瘤细胞的生长有抑制作用。这些数据表明，杂交脂质体可能是一种新的化疗药物在治疗癌症。

项目成果

期刊论文数量（43）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

通阪栄一, 吉永武史, 後藤雅宏, 上岡龍一, 古崎新太郎: "レクチンの認識機能を有するハイブリッド型リポソームの調製"膜. 27・4. 202-208 (2002)

户坂英一、吉永武、后藤正博、神冈龙一、古崎慎太郎：“具有凝集素识别功能的混合脂质体的制备”27・4（2002）。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Induction of Apoptosis by Hybrid Liposomes without Antitumor Drugs toward Human Breast Tumor Cells

不含抗肿瘤药物的混合脂质体诱导人乳腺肿瘤细胞凋亡

DOI：
发表时间：
2003
期刊：
Journal of Chemical Engineering of Japan 36・9
影响因子：
0
作者：
Y Kadota;C.Taniguchi;S.Masuhara;S.Yamamoto;S.Furusaki;M.Iwahara;K.Goto;Y.Matsumoto;R.Ueoka;Yutaka Kadota;Hideaki Nagami
通讯作者：
Hideaki Nagami

Enhanced Inhibitory Effects of Extracts from Ginkgo biloba L.Leaves Encapsulated in Hybrid Liposomes on the Growth of Tumor Cells in vitro

混合脂质体包埋银杏叶提取物对体外肿瘤细胞生长的增强抑制作用