Development and application of novel w/o/w emulsion for the chemoembolization therapy of hepatocellular carcinoma

新型w/o/w乳剂在肝细胞癌化疗栓塞治疗中的研制及应用

• 批准号: 07672320
• 负责人: HINO Tomoaki
• 金额: $ 0.19万
• 依托单位: Gifu Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672320/
• 关键词: w; o; w emulsion; transcatheter arterial ambolization therapy; epirubicin hydrochloride; lipiodol; acute toxicity; hemolysis; Wエマルジョン; 化学塞栓療法; 塩酸エピルビシン; 肺水腫

W/o/w emulsion (WOWE) encapsulating water-soluble anticancer agent (epirubicin hydrochloride, EPI) was prepared by two-step amulsification method. Aqueous and oil phases used were nonionic (iohexol) and oily (lipiodol) contract media, respectively. The agents added in inner and outer aqueous phases were polyoxyethylene hydrated caster oil 60 and gelatin, respectively.The WOWE was stable emulsion which could encapsulate large amount of EPI and the viscosity was small. The hemolysis percentage was less than that of the o/w emulsion (OWE) used for transcatheter chemoembolization therapy (TAE) conventionally.The acute toxicities of WOWE and OWE were investigated. The emulsions with and without EPI were administered to the tail vein of rats. The rats administered OWE (*1.5 ml/kg) were deceased within 2 days by pulmonary edema. The rats administered WOWE (*2.0 ml/kg) encapsulating EPI were deceased 7-9 days after administration by the toxicity of EPI.Bleeding and ulcer in the stomach and size reduction of thymus gland were observed in these deceased rats. These pathological damage in the stomach and thymus gland were observed in the rats administered less amounts of OWE than WOWE.This result suggests that the encapsulation of EPI in the WOWE droplets reduced the acute toxicity of EPI.Therefore, the WOWE newly prepared by us was safer than OWE and desirable formulation for TAE.The effectiveness of WOWE is investigated now and the possible clinical application of WOWE is under investigation.

采用两步乳化法制备了水溶性抗癌药盐酸表阿霉素（EPI）的W/O/W型乳剂。使用的水相和油相分别为非离子（碘海醇）和油性（碘油）接触介质。内、外水相中分别加入聚氧乙烯水合蓖麻油60和明胶，制得的WOWE是一种稳定的乳液，可包封大量EPI，粘度小。溶血率低于常规经导管化疗栓塞（TAE）用的O/W乳剂（OWE）。将含有和不含有EPI的乳液施用于大鼠的尾静脉。给予OWE（*1.5 ml/kg）的大鼠在2天内因肺水肿死亡。用WOWE（* 2.0ml/kg）包封EPI后7-9天，大鼠因EPI毒性而死亡，胃出血、溃疡，胸腺缩小。结果表明，WOWE液滴中包封了EPI，降低了EPI的急性毒性，因此，我们研制的WOWE比OWE更安全，是TAE的理想剂型，目前正在研究WOWE的有效性，并可能在临床上应用。

项目成果

T.Hino et al.: "Evaluation of acute toxicity of epirubicin hydrochloride-encapsulating w/o/w emulsion administered to rat for the transcatheter embolization therapy for hepatocellular carcinoma" Drug Delivery System. (in print). (1997)

T.Hino 等人：“对大鼠进行肝细胞癌经导管栓塞治疗的盐酸表柔比星包封的 w/o/w 乳剂的急性毒性评估”药物输送系统。

日野知証他: "肝細胞癌の塞栓療法のための塩酸エピルビジン封入W/O/W型エマルションのラットに対する急性毒性の評価" Drug Delivery System. (印刷中). (1997)

Chisho Hino 等人：“含有盐酸表柔比丁的 W/O/W 乳剂用于肝细胞癌栓塞治疗的大鼠急性毒性评估”药物输送系统（1997 年出版）。

日野 知証 他: "肝細胞癌の塞栓療法のための塩酸エピルビシン封入W/O/Wエマルジョンのラットに対する急性毒性の評価" Drug Delivery System. (印刷中). (1997)

Chisho Hino 等人：“含有盐酸表柔比星的 W/O/W 乳剂用于肝细胞癌栓塞治疗的大鼠急性毒性评估”药物输送系统（1997 年出版）。

日野 知証: "肝細胞癌の塞栓療法のための塩酸エピルビシン封入W/O/Wリピオドールエマルジョンの設計" Drug Delivery System. 10. 115-119 (1995)

Chisho Hino：“用于肝细胞癌栓塞治疗的 W/O/W 碘化油乳剂的设计”，药物输送系统。 10. 115-119 (1995)。