JP6923922B2 - ジンセノサイドf2を有効成分として含む肝がんの予防または治療用組成物 - Google Patents
ジンセノサイドf2を有効成分として含む肝がんの予防または治療用組成物 Download PDFInfo
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- JP6923922B2 JP6923922B2 JP2018095423A JP2018095423A JP6923922B2 JP 6923922 B2 JP6923922 B2 JP 6923922B2 JP 2018095423 A JP2018095423 A JP 2018095423A JP 2018095423 A JP2018095423 A JP 2018095423A JP 6923922 B2 JP6923922 B2 JP 6923922B2
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- liver cancer
- ginsenoside
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Description
また、本発明はジンセノサイドF2を有効成分として含む肝がんの予防または改善用健康機能食品組成物に関する。
本発明の他の目的は、ジンセノサイドF2を有効成分として含む肝がんの予防または改善用健康機能食品組成物を提供することにある。
本発明における用語、「ジンセノサイドF2」は、高麗人参や紅参などの主要な活性成分であるサポニンの一種であり、PPD(protopanaxadiol)系に属するジンセノサイドを意味する。
本発明における用語、「予防」は、本発明におけるジンセノサイドF2を個体に投与して肝がんの発病を抑制したり、遅らせるすべて行為を意味することができる。
本発明において、前記薬学組成物は肝がん細胞に特異的に細胞死滅効果を示すことができ、前記肝がん細胞は、ヒト肝がん細胞株であるHep3Bまたはマウス肝がん細胞株であるHepa1−6であり得るが、これらに限定されるものではなく、一般的な肝がん細胞すべてに死滅効果を示すことができる。
本発明において前記薬学組成物は、免疫細胞の数を増加させることができる。
本発明において、用語「ジンセノサイドF2」及び「予防」は前記で説明した通りである。
本発明における用語、「食品」は、肉類、ソーセージ、パン、チョコレート、キャンディ類、スナック類、菓子類、ピザ、ラーメン、その他麺類、ガム類、アイスクリーム類を含む酪農製品、各種スープ、飲料、お茶、ドリンク剤、アルコール飲料、ビタミン複合剤、健康機能食品及び健康食品などがあり、通常の意味の食品をすべて含む。
前記組成物は、生理学的に許容可能な担体をさらに含むことができるが、担体の種類は特に限定されず、当該技術分野で通常使用される担体であれば、いずれのものであっても使用することができる。
本発明において用語、「ジンセノサイドF2」は前記で説明した通りである。
前記の「薬学的に有効な量」は、医学的治療に適用可能な合理的な受益/リスク比で疾患を治療するのに十分な量を意味し、有効容量水準は個体の種類及び重症度、年齢、性別、薬物の活性、薬物に対する敏感度、投与時間、投与経路及び排出比率、治療期間、同時に使用された薬物を含む要素及びその他の医学分野でよく知られている要素により決定してもよい。例えば、ジンセノサイドF2を含む前記薬学組成物は、1日に0.0001〜1000mg/kgで、具体的には、0.001〜100mg/kgで投与してもよい。
ジンセノサイドF2の製造方法は次の通りである。
具体的には、高麗人参、西洋参及び竹節参を含む高麗人参の葉及び根を20倍体積の80%酒精を加えて2回抽出して、乾燥し粗サポニンを獲得した。前記粗サポニンを水に再度溶解させて、HP−20樹脂に吸着させた後、水100%で洗浄し、糖を除去した。糖を除去した後、40%酒精で1次洗浄してプロトパナキサトリオール(protopanaxatriol)系であるジンセノサイドRe及びRg1を優先的に除去した。その後、80%酒精で洗浄した後、乾燥して、溶出されたプロトパナキサジオール(protopanaxadiol)系であるジンセノサイドRb1、Rb2、Rc及びRdを獲得した。前記プロトパナキサジオールジンセノサイド混合物を基質として使用して韓国公開特許第2013−0134930号に記載された方法に基づいて70%以上のジンセノサイドF2を獲得した。前記ジンセノサイドF2をODS樹脂を利用して、吸着した後、ジンセノサイドF2を得るのに適正な濃度の酒精を濃度区配分で連続的に流して、95%以上の純度の高いジンセノサイドF2分画を得た。
実施例2−1:ヒト肝がん細胞株、マウス肝がん細胞株及び正常な肝細胞に対する死滅効果の比較
前記実施例1で製造したジンセノサイドF2をヒト肝がん細胞株であるHep3B細胞、マウス肝がん細胞株であるHepa1−6細胞及びマウス正常肝細胞に様々な濃度(10〜60μM)で処理した後、24時間経過した後、細胞生存率を測定するのに使用されるEZ−CYTOX(daeillab service、大韓民国)を使用して製造会社が提供する実験方法に応じて、前記細胞の生存率を測定した。
位相差顕微鏡と蛍光顕微鏡を使用してジンセノサイドF2のヒト肝がん細胞株(Hep3B)の死滅効果を確認した。
実施例2−3:マウス肝がん細胞株に対する死滅効果
DNAの分解の程度を確認して、ジンセノサイドF2のマウス肝がん細胞株(Hepa1−6)に対する死滅効果を確認した。
実施例3:ジンセノサイドF2の肝がんの形成抑制効果
実施例3−1:肝がんの形成誘導マウスの製造
肝がん誘導物質であるジエチルニトロソアミン(Diethylnitrosamine、DEN)を20mg/kgの濃度にして、生後14日の雄マウスの腹腔内に注射して肝がんの形成を誘導した。生後20週齢から担体(オリーブオイル)、またはジンセノサイドF2(50mg/kg)を週3回処理した後、20週後に犠牲させて肝がん形成の抑制程度を確認した。
前記実施例3−1で犠牲させたマウスを開腹して肝臓を摘出した後、担体処理群及びジンセノサイドF2処理群のがん組織の大きさ、個数及び重量を比較した。
実施例3−3:ジンセノサイドF2の肝機能保存効果
前記実施例3−1で犠牲させたマウスの腹部大動脈から血液を採取して遠心分離器を用いて3,300rpmの条件で10分間遠心分離した後、血清のみを分離した。その後、血清中のアラニンアミノ基転移酵素(alanine aminotransferase、ALT)、アスパラギン酸アミノ基転移酵素(aspartate aminotransferase、AST)、トリグリセリド(triglyceride)をアイデックス(IDEXX Laboratories、米国)社のキットを使用して製造会社で提供する実験方法に応じて、ベットテスト(VetTEST、IDEXX、米国)で測定した。
したがって、ジンセノサイドF2は肝がんの形成を抑制すると同時に、肝の機能を保存することができる効果を示すことを確認した。
前記実施例3−1で犠牲させたマウスを開腹して肝臓を摘出した後、肝の組織学的変化を観察するために、H&E(ヘマトトキシン及びイオシン)染色を実施した。
Claims (6)
- ジンセノサイドF2を有効成分として含む、非アルコール性肝がんの予防または治療用薬学組成物。
- 前記薬学組成物が、肝がん細胞に特異的に細胞死滅効果を示すものである、請求項1に記載の薬学組成物。
- 前記薬学組成物が、アラニンアミノ基転移酵素(alanine aminotransferase、ALT)またはアスパラギン酸アミノ基転移酵素(aspartate aminotransferase、AST)の発現を減少させるものである、請求項1に記載の薬学組成物。
- 前記薬学組成物が、免疫細胞の数を増加させるものである、請求項1に記載の薬学組成物。
- 前記免疫細胞が、CD8 T細胞、ナチュラルキラーT細胞、及び大食細胞を含む群から選択されたいずれか一つ以上であるものである、請求項4に記載の薬学組成物。
- ジンセノサイドF2を有効成分として含む、非アルコール性肝がんの予防または改善用食品組成物。
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