JP7486753B2 - D-アロースを有効成分として含む、腎細胞癌を治療又は予防するための組成物、及びそれを用いた癌を治療又は予防する方法 - Google Patents
D-アロースを有効成分として含む、腎細胞癌を治療又は予防するための組成物、及びそれを用いた癌を治療又は予防する方法 Download PDFInfo
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Description
[2] 前記経腸管投与が、経口投与である、請求項1に記載の組成物。
[3] 前記D-アロースが、1mg/kg体重/日~1000mg/kg体重/日で、投与される、請求項1又は2に記載の組成物。
[4] 前記D-アロースが、D-アロースおよび/またはその誘導体および/またはその混合物である、請求項1~3のいずれか1項に記載の組成物。
[5] D-アロースの誘導体が、D-アロースのカルボニル基がアルコール基となった糖アルコール、D-アロースのアルコール基が酸化したウロン酸、D-アロースのアルコール基がアミノ基で置換されたアミノ糖、及びD-アロースの任意のヒドロキシ基が水素原子、ハロゲン原子、アミノ基、カルボキシル基、ニトロ基、シアノ基、低級アルキル基、低級アルコキシ基、低級アシル基、低級アルカノイルオキシ基、低級アルコキシカルボニル基、モノ又はジ低級アルキル置換アミノ基、アラルキル基、アリール基又はヘテロアリール基で置換されたD-アロース誘導体からなる群から1又は複数選択されるD-アロース誘導体である、請求項4に記載の組成物。
[6] 医薬品である、請求項1~5のいずれか一項に記載の組成物。
[7] 食品である、請求項1~5のいずれか一項に記載の組成物。
[8] 前記食品が、保健機能食品またはダイエタリーサプリメントである、請求項7に記載の組成物。
[9] 前記保健機能食品が、特定保健用食品または栄養機能食品である、請求項8に記載の組成物。
を含む、対象における腎細胞癌を治療又は予防する方法。
[11] 前記経腸管投与が、経口投与である、請求項10に記載の方法。
[12] 前記D-アロースが、1mg/kg体重/日~1000mg/kg体重/日で、投与される、請求項10又は11に記載の方法。
[13] 前記D-アロースが、D-アロースおよび/またはその誘導体および/またはその混合物である、請求項10~12のいずれか1項に記載の方法。
[14] D-アロースの誘導体が、D-アロースのカルボニル基がアルコール基となった糖アルコール、D-アロースのアルコール基が酸化したウロン酸、D-アロースのアルコール基がアミノ基で置換されたアミノ糖、及びD-アロースの任意のヒドロキシ基が水素原子、ハロゲン原子、アミノ基、カルボキシル基、ニトロ基、シアノ基、低級アルキル基、低級アルコキシ基、低級アルカノイル基、低級アルカノイルオキシ基、低級アルコキシカルボニル基、モノ又はジ低級アルキル置換アミノ基、アラルキル基、アリール基又はヘテロアリール基で置換されたD-アロース誘導体からなる群から1又は複数選択されるD-アロース誘導体である、請求項13に記載の方法。
[15] 前記組成物が、医薬品として経口投与される、請求項10~14のいずれか一項に記載の方法。
[16] 前記組成物が、食品として経口投与される、請求項10~14のいずれか一項に記載の方法。
[17] 前記食品が、保健機能食品またはダイエタリーサプリメントである、請求項16に記載の方法。
[18] 前記保健機能食品が、特定保健用食品または栄養機能食品である、請求項17に記載の方法。
<腎細胞癌異種移植マウスの作製方法>
本実験は2種類のヒト腎細胞癌細胞株を(Caki-1、ACHN)を用いた。各細胞は10%ウシ胎児血清、およびHEPES緩衝液とpenicillin-streptomycinを含むRPMI-1640培養液(2000mg D-グルコース/L)を使用し、37℃で5% CO2の湿潤環境で培養した。腎細胞癌異種移植マウスモデルは培養細胞をMEM培養液で1.0×105 cells/mLの細胞懸濁液に調製し、Female athymic nude mice(BALB/c nu/nu、6週齢)の大腿部皮下組織に0.1mL注入し、その1週間後に腫瘍体積が200mm3以上であることを確認し、その後の実験に用いた。
<大腸癌異種移植マウスの作製方法>
Male athymic nude mice (BALB/c Nude (nu/nu) mice)の大腿部皮下組織に、ヒト大腸癌細胞株(DLD-1)を2.0×106 個含む細胞懸濁液を注入し、腫瘍体積が約100~150mm3に達した日を「day0」とし、D-アロース又はD-グルコースの投与を開始した。
腫瘍体積が約100mm3に達した大腸癌異種移植マウスにおいて、400mg/kgのD-アロース又はD-グルコースを腹腔内投与した。溶媒として生理食塩水を用い、0.2mlに調整し、1日1回、計30日間投与した。6日毎に腫瘍体積を測定した。その結果、D-アロース投与群の腫瘍体積は、D-グルコース群と比較して、投与開始18日目以降に有意に小さかった(Mann-Whitney U test)(図7(A))。
腫瘍体積が約100~150mm3に達した大腸癌異種移植マウスにおいて、100mg/kgのD-アロース又はD-グルコースを経口投与した。溶媒として蒸留水を用い、0.2mlに調製し、1日1回、計30日間投与した。6日毎に腫瘍体積を測定した。その結果、D-アロース投与群とD-グルコース投与群の腫瘍体積に有意な差は認められなかった(Mann-Whitney U test)(図7(B))。
100mm dishに対し、ヒト腎細胞癌細胞株(Caki-1又はACHN)5.0×105個を播種し、24時間培養後にDMSO又はD-アロース(50mM)で1時間共培養したのち、10μM 2,7-Dichlorofluorescin diacetate(DCF-DA;D6883、Sigma-Aldrich、USA)を添加し、37℃で30分間静置した。細胞はトリプシン化により回収され、5分間3500×gで遠心分離し集められたのち、細胞を氷冷PBSで再懸濁し、CytoFLEX S(Beckman Coulter、CA、USA)を用いてDCF-DA蛍光を検出した。全ての実験を3回実施し、データはCytExpertソフトウェアを使用して分析し、平均値±SEとして示した(図8)。
100mm dishに対し、ヒト腎細胞癌細胞株(Caki-1又はCaki-2)5.0×105個を播種し、24時間培養後に、D-アロース(10、25、50mM)で共培養した。処置48時間後に細胞を回収し、タンパク質を抽出し、各タンパク質濃度をBio-Rad Protein Assay Kit(Bio-Rad, Laboratories, Inc. USA)で測定した。タンパク質サンプル(40μg)を10% Mini-PROTAN TGX Precast Gel(Bio-Rad)上で電気泳動させ、Trans-Blot Turbo transfer system(Bio-Rad)を使用しPVDF Western Blotting Membranesに転写した。1時間のブロッキング処理後(Superblock T20、Thermo、Rockford. IL、USA)、抗TXNIP抗体(D5F3E, CST, USA. 1:1000)を1次抗体としてiBind Flex Western System(Thermo)を使用し反応させた。ローディングコントロールとしてβ-actin(ab8227, abcam, CamBridge, UK, 1:1000)を使用した。
Claims (8)
- D-アロースを有効成分として含み、50mg/kg体重/日~500mg/kg体重/日の用量で経腸管投与され、
前記D-アロースが、D-アロースおよび/またはその誘導体および/またはその混合物であり、
前記D-アロースの誘導体が、D-アロースのカルボニル基がアルコール基となった糖アルコール、D-アロースのアルコール基が酸化したウロン酸、及び、D-アロースのアルコール基がアミノ基で置換されたアミノ糖からなる群から1又は複数選択されるD-アロース誘導体であることを特徴とする、腎細胞癌を治療又は予防するための組成物。 - 前記経腸管投与が、経口投与である、請求項1に記載の組成物。
- さらに、賦形剤、安定剤、保存剤、結合剤、および/または崩壊剤が含まれる、請求項1又は2に記載の組成物。
- 充填剤、増量剤、溶解促進剤、湿潤剤、および/または潤滑剤が含まれる、請求項3に記載の組成物。
- 医薬品である、請求項1~4のいずれか一項に記載の組成物。
- 食品である、請求項1~4のいずれか一項に記載の組成物。
- 前記食品が、保健機能食品またはダイエタリーサプリメントである、請求項6に記載の組成物。
- 前記保健機能食品が、特定保健用食品または栄養機能食品である、請求項7に記載の組成物。
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WO2007010973A1 (ja) | 2005-07-20 | 2007-01-25 | Teikoku Seiyaku Co., Ltd. | D-アロースおよびd-プシコースの抗神経因性疼痛効果の利用 |
WO2007026820A1 (ja) | 2005-08-31 | 2007-03-08 | National University Corporation Kagawa University | D-アロースによる高血圧、心肥大発症抑制効果の利用 |
WO2008056452A1 (fr) | 2006-11-09 | 2008-05-15 | National University Corporation Kagawa University | Utilisation de sucre rare pour ralentir le début ou l'évolution de la mobilité réduite associée avec la sclérose latérale amyotrophique |
JP2015182998A (ja) | 2014-03-26 | 2015-10-22 | 公立大学法人福岡女子大学 | 非アルコール性脂肪性肝炎の改善剤および改善用栄養組成物 |
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US20220152068A1 (en) * | 2019-03-20 | 2022-05-19 | National University Corporation Kagawa University | Drug delivery carrier utilizing property of d-allose being uptaken by cancer cell, drug delivery method, and composition for treating renal cell carcinoma |
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EP4159219A1 (en) | 2023-04-05 |
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