{"created":"2023-07-27T07:00:11.985024+00:00","id":60040,"links":{},"metadata":{"_buckets":{"deposit":"fff4a899-409d-47e9-b21f-7b1ddd7bc470"},"_deposit":{"created_by":18,"id":"60040","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"60040"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00060040","sets":["2812:2813:2837"]},"author_link":["20795","95704"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"1999-03-08","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"3p.","bibliographicVolumeNumber":"1995 – 1996","bibliographic_titles":[{"bibliographic_title":"平成8(1996)年度 科学研究費補助金 基盤研究(C) 研究成果報告書概要"},{"bibliographic_title":"1996 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"本研究では、強い制癌活性を有し、有望な経口白金剤の一つとして開発研究を進めているtrans, cis, cis-bis (n-butyrato) (1R, 2R-cyclohexanediamine) (oxalato) platinum (IV) (C4-OHP)とtrans,cis, cis-bis (n-valerato) (1R, 2R-cyclohexanediamine) (oxalato) platinum (IV) (C5-OHP)について、先ず、経口投与での制癌効果を評価した。担癌マウスにC4-OHP又はC5-OHPを経口投与し、生存日数から制癌効果を評価した。C4-OHPではコントロール群に比べ有意な生存日数の延長は認められなかったが、C5-OHPでは有意な延長が観察され、C5-OHPが確かに経口投与で制癌作用を示すことが明らかになった。以下、C5-OHPを主な対象とした。次いで、C5-OHPについてその高感度HPLC分析法を研究した。試料からC5-OHPを酢酸エチルで抽出した後、HPLCに適用した。HPLCでは、分離カラムにODSカラム、溶離液に水/メタノールを用いた逆相分配系で分離溶出し、210nmで直接紫外吸収検出することにより高感度にC5-OHPを定量できた。検出下限は50nMと高感度であり、血漿、尿、細胞の何れの試料についても分析が可能であった。更に、活性代謝物の検索を行い、活性代謝物についても高感度HPLC分析法を開発した。先ずグラジエント溶出HPLCを用いて活性代謝物を検索した結果, (1R, 2R-cyclohexanediamine) (oxalato) platinum (II) (OHP)が同定され、in vitroでは定量的に生成することが分かった。そこで、OHPの高感度HPLC分析法を研究した。OHPは逆相分配系で分離溶出後、ポストカラムで亜硫酸水素ナトリウムと反応させて誘導化し,290nmで紫外吸収検出することにより、高感度に定量できた。検出下限は50nMと高感度で,限外ろ過による除タンパクだけで血漿、尿及び細胞の何れの試料についても分析が可能であった。","subitem_description_type":"Abstract"},{"subitem_description":"This study was conducted to develop highly sensitive method for determining orally active antitumor platinum complexes of the next generation and their active metabolites. The complexes used were trans, cis, cis-bis (n-butyrato) (1R,2R-cyclohexanediamine) (oxalato) platinum (IV) (C4-OHP) and trans, cis, cis-bis (n-valerato) (1R,2R-cyclohexanediamine) (oxalato) platinum (IV) (C5-OHP), which are expected as promising oral agents because of their high antitumor activities in screening tests. Oral antitumor activities of C4-OHP and C5-OHP were first evaluated in mice bearing mouse leukemia L 1210. Significant increase in life span was observed with C5-OHP-treated group but not with C4-OHP-treated group. Therefore, subsequent study was made mainly on C5-OHP.Then, HPLC method for determining C5-OHP in biological samples was developed. C5-OHP was extracted with ethyl acetate and then subjected to reversed-phase HPLC.C5-OHP was chromatographed on an ODS column with water/methanol eluent and spectrophotometrically detected by at 210 nm. This method was found to be highly sensitive, giving the detection limit of 50 nM.C5-OHP in plasma, urine and cultured cell samples could be determined. Next, examination of active metabolites of C5-OHP was made by means of HPLC,revealing that (1R,2R-cyclohexanediamine) (oxalato) platinum (II) (OHP) was yielded from C5-OHP and the production was almost quantitative. Therefore, HPLC method for determining OHP in biological samples was developed. OHP was chromatographed in reversed-phase mode followed by post-column derivatization by sodium bisulfite and spectrophotometric detection at 290 nm. This method was also sensitive, giving the detection limit of 50 nM.The method required no pretreatment of samples but deproteinization by ultrafiltration and applicable to plasma, urine and cultured cell samples.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:07672312, 研究期間(年度):1995 – 1996","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「経口投与で制癌作用を示す次世代制癌性白金錯体及びその活性代謝物の高感度分析法」課題番号07672312\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） \n（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-07672312/076723121996kenkyu_seika_hokoku_gaiyo/）を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医薬学部","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00066291","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=80143915"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=80143915","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672312/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672312/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-07672312/076723121996kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-07672312/076723121996kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-06-09"}],"displaytype":"detail","filename":"PH-PR-KIZU-R-kaken 1999-3p.pdf","filesize":[{"value":"94.0 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"PH-PR-KIZU-R-kaken 1999-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/60040/files/PH-PR-KIZU-R-kaken 1999-3p.pdf"},"version_id":"3af7a75a-df34-46a9-b62c-e2b0bc512788"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"経口投与で制癌作用を示す次世代制癌性白金錯体及びその活性代謝物の高感度分析法","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"経口投与で制癌作用を示す次世代制癌性白金錯体及びその活性代謝物の高感度分析法"},{"subitem_title":"Highly Sensitive Determination Method for Orally Active Antitumor Platinum Complexes of Next Generation and Their Active Metabolites","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2837"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-06-09"},"publish_date":"2022-06-09","publish_status":"0","recid":"60040","relation_version_is_last":true,"title":["経口投与で制癌作用を示す次世代制癌性白金錯体及びその活性代謝物の高感度分析法"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T12:54:18.835317+00:00"}