著者

柿木 充史 金尾 義治 田中 哲郎 細川 宣嗣

出版者

福山大学薬学部

雑誌

福山大学薬学部研究年報 = Annual report of the Faculty of Pharmacy & Pharmaceutical Sciences, Fukuyama University (ISSN:0288724X)

巻号頁・発行日

no.27, pp.42-43, 2009-12-25

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Paclitaxel (PTX) is an antitumor agent for the treatment of various human cancers. Cremophor EL and ethanol are used to formulate PTX in commercial injection solutions, because of its poor solubility in water. However, these agents cause severe allergic reaction upon intravenous administration. The aim of this study is to synthesize water-soluble macromolecular prodrugs of PTX for enhancing the therapeutic efficacy. Poly(vinyl alcohol) (PVA, 80 kDa), water-soluble synthetic polymer, was used as a drug carrier which is safe and stable in the body. The 2'-hydroxyl group of PTX was reacted with succinic anhydride and then carboxylic group of the succinyl spacer was coupled to PVA via ethylene diamine spacer, resulting the water-soluble prodrug of poly(vinyl alcohol)-paclitaxel conjugate (PVA-SPTX). The solubility of PTX was greatly enhanced by the conjugation to PVA. The release of PTX from the conjugate was accelerated at the neutral to basic conditions in in vitro release experiment. [125 I]-labeled PVA-SPTX was retained in the blood circulation for several days and was gradually distributed into the tumorous tissue after intravenous injection to the tumor-bearing mice. PVA-SPTX inhibited the growth of sarcoma 180 cells subcutaneously inoculated in mice. It was suggested that the water-solubility of PTX was markedly enhanced by the conjugation to PVA, and PVA-SPTX effectively delivered PTX to the tumorous tissue due to the enhanced permeability and retention (EPR) effect.Paclitaxel (PTX) is an antitumor agent for the treatment of various human cancers. Cremophor EL and ethanol are used to formulate PTX in commercial injection solutions, because of its poor solubility in water. However, these agents cause severe allergic reaction upon intravenous administration. The aim of this study is to synthesize water-soluble macromolecular prodrugs of PTX for enhancing the therapeutic efficacy. Poly(vinyl alcohol) (PVA, 80 kDa), water-soluble synthetic polymer, was used as a drug carrier which is safe and stable in the body. The 2'-hydroxyl group of PTX was reacted with succinic anhydride and then carboxylic group of the succinyl spacer was coupled to PVA via ethylene diamine spacer, resulting the water-soluble prodrug of poly(vinyl alcohol)-paclitaxel conjugate (PVA-SPTX). The solubility of PTX was greatly enhanced by the conjugation to PVA. The release of PTX from the conjugate was accelerated at the neutral to basic conditions in in vitro release experiment. [125 I]-labeled PVA-SPTX was retained in the blood circulation for several days and was gradually distributed into the tumorous tissue after intravenous injection to the tumor-bearing mice. PVA-SPTX inhibited the growth of sarcoma 180 cells subcutaneously inoculated in mice. It was suggested that the water-solubility of PTX was markedly enhanced by the conjugation to PVA, and PVA-SPTX effectively delivered PTX to the tumorous tissue due to the enhanced permeability and retention (EPR) effect.

著者

木村 久雄 小川 勤 柿木 充 松本 新 濱野 翼 月橋 文孝

出版者

社団法人日本鉄鋼協会

雑誌

鐵と鋼 : 日本鐡鋼協會々誌 (ISSN:00211575)

巻号頁・発行日

vol.92, no.12, pp.748-754, 2006-12-01

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Phase diagrams for the CaO-SiO_2-FeO_x-Al_2O_3 or -MgO systems at various oxygen partial pressures are necessary for the design of raw material for ironmaking, the analysis of smelting reaction and sintering process. To clarify the effect of Al_2O_3 or MgO content on the formation of melts in the sintering process is important for the development of new sinter. In this study, liquidus for the CaO-SiO_2-FeO_x-Al_2O_3 or -MgO systems at various oxygen partial pressures were observed at 1573K by using chemical equilibration technique. The liquid phase area changed with adding Al_2O_3 or MgO. The effect of the Fe^<3+>/Fe^<2+> ratio on the melting mechanism is discussed.