yrammuS 要概12笠井 均Hitoshi KASAI古荘 義雄Yoshio FURUSHO新規ナノ薬剤作製法の開発と制癌剤への応用（2012年採択）Creation of Novel Nanodrugs and Application for The Anticancer Agent(Project 2012)アミジン－カルボン酸塩橋を利用した分子集積体の構築と応用（2012年採択）Construction and Application of Molecular Assemblies by Utilizing Amidinium-Carboxylate Salt Bridge(Project 2012)25従来の薬化合物の設計としては，薬理効果を有する化合物に水溶性の置換基を付けることが一般的といえるが，体内に投与した後，腎臓から濾過されやすい上，正常組織にも拡散しやすいという問題点が現存した．本申請研究では，抗癌薬化合物にコレステロール誘導体などの難水溶性置換基を化学的に連結することや２量体化などを施すという従来とは真逆の薬剤設計を遂行することに加えて，有機ナノ粒子の作製法である再沈法を駆使することにより，100 nm以下のナノプロドラッグを作製する技術の確立に成功した．その結果，腫瘍組織の細胞内にまで効率的なドラッグデリバリーシステムを構築可能であることが分かり，近い将来での実用化が期待される．For the design of the conventional drug compound, it was common to add a water-soluble substituent to a compound having a pharmacological effect. However, in the case of anti-cancer drugs, it was reported that the water-soluble compounds given by using intravenous administration were easily filtered from kidney or dif-fused even in normal tissue. On the other hand, it is known that, when µm-sized drugs with more than 100 nm were administrated in the blood, they tended to be transported to the liver after macrophages were phago-cytosed. In this project, in order to overcome the above problems, we are designing the novel anti-cancer drugs composed in the dimer or the compounds to which the poorly water-soluble substituent such as a cho-lesterol derivative are chemically linked. In addition, by utilizing our technique of reprecipitation for fabrica-tion of organic nanoparticles, we could establish the method to obtain 100 nm or less of the nano-prodrugs. As a result, we have found that our anti-cancer nano-prodrugs themselves could be delivered even within the cells of the tumor tissue, and are aiming at practical application of this nano-prodrugs in the near future.主鎖にアミジン基をもつポリマーと両末端にカルボキシル基をもつテレケリックなポリマーを溶液中で混合したのち，溶媒を留去することで，アミジンーカルボン酸塩橋で架橋された三次元ネットワーク構造をもつ超分子ポリマーゲルが得られることを見出した．これらのポリマーゲルは従来の水素結合由来のものに比べて強靭なものである一方，温度変化に反応して粘弾性を可逆的に大きく変化させることが明らかになった．また，一連の検討結果の過程で，ポリアミジンが低分子量のポリエチレングリコールと均一に相溶し，この２成分系混合物が炭酸ガスを効率良くトラップし，窒素気流下では炭酸ガスを放出することを見出した．We found that mixing polymers having amidine group in the main chain and carboxy-terminated telechelic polymers in organic solution gave supramolecular polymer gels that have 3-dimensional network structure with amidinium-carboxylate salt bridge cross-linking after removal of the organic solvent. The supramolecu-lar polymer gels turned out to be more stiff than conventional supramolecular polymer gels with hydro-概要 Summary
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