JPWO2006095798A1 - フィトステロールを含んだリポソームを含有する抗癌用経口組成物、該リポソームによる癌の予防又は治療 - Google Patents
フィトステロールを含んだリポソームを含有する抗癌用経口組成物、該リポソームによる癌の予防又は治療 Download PDFInfo
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- JPWO2006095798A1 JPWO2006095798A1 JP2007507167A JP2007507167A JPWO2006095798A1 JP WO2006095798 A1 JPWO2006095798 A1 JP WO2006095798A1 JP 2007507167 A JP2007507167 A JP 2007507167A JP 2007507167 A JP2007507167 A JP 2007507167A JP WO2006095798 A1 JPWO2006095798 A1 JP WO2006095798A1
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- liposome
- cancer
- phytosterol
- liposomes
- oral composition
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Abstract
Description
Hirofumi Takeuchi et al. ,"Enteral Absorption of Insulin in Rats from Mucoadhesive Chitosan-Coated Liposomes", Pharmaceutical Research,13(6),896-901,1996 Muramatsu K et al.,"Dipalmitoylphosphatidylcholine Liposomes with Soybean-Derived Sterols and Cholesterol as a Carrier for the Oral Administration of Insulin in Rats",Biological & Pharmaceutical Bulletin, 19(8), 1055-1058, 1996 Kazunori Iwanaga et al.," Application of surface-coated liposomes for oral delivery of peptide: Effects of coating the liposome's surface on the GI transit of insulin",Journal of Pharmaceutical Sciences,88, 248-252, 1999 Yoshie Maitani et al.," Oral administration of recombinant human erythropoietin in liposomes in rats: Influence of lipid composition and size of liposomes on bioavailability", Journal of Pharmaceutical Sciences,85, 440-445,1996
項1.フィトステロールを含んだリポソームを含有する抗癌用経口組成物。
項2.フィトステロールが、β−シトステロール、カンペステロール、スティグマステロール、ブラシカステロール、エルゴステロール及びエルゴスタディエノールからなる群から選択される少なくとも1種である項1に記載の経口組成物。
項3.リポソームにおけるフィトステロール含有量が1〜33重量%である項1に記載の経口組成物。
項4.抗癌作用が癌転移抑制である項1〜3のいずれかに記載の経口組成物。
項5.経口組成物が食品組成物である項1〜4のいずれかに記載の組成物。
項6.経口組成物が医薬組成物である項1〜4のいずれかに記載の経口組成物。
項7.フィトステロールを含んだリポソームの癌転移抑制に有効な量を対象者に経口投与することを特徴とする癌を予防又は治療する方法。
項8.フィトステロールが、β−シトステロール、カンペステロール、スティグマステロール、ブラシカステロール、エルゴステロール及びエルゴスタディエノールからなる群から選択される少なくとも1種である項7に記載の癌を予防又は治療する方法。
項9.経口投与されるリポソームの量が、成人一人1日あたり、10mg〜10000mgである項7又は8に記載の癌を予防又は治療する方法。
項10.癌を予防又は治療するための、フィトステロールを含んだリポソームの使用。
項11.フィトステロールが、β−シトステロール、カンペステロール、スティグマステロール、ブラシカステロール、エルゴステロール及びエルゴスタディエノールからなる群から選択される少なくとも1種である項10に記載の使用。
β−シトステロール及び卵黄レシチンを膜構成成分とするリポソームの調製
薄膜水和法によりリポソームを調製した。卵黄レシチンとβ−シトステロールのモル比が2:1となるように、クロロホルムで500mMの濃度に溶解した卵黄レシチンを160μl、250mMの濃度に溶解したβ−シトステロールを160μl量りとり、両溶液を混合し、クロロホルムを加えた。ロータリーエバポレーターにてクロロホルムを減圧下留去し、真空乾燥させて薄膜を作成した。この薄膜に卵黄レシチン濃度が20mMとなるようにリン酸緩衝生理食塩水(PBS)を4ml加え、ボルテックスミキサーで処理し、液体窒素による凍結融解を3回行うことによりリポソーム懸濁液を得た。この懸濁液をプローブ型ソニケーターで10分間処理し、リポソーム組成物を得た。
コレステロール及び卵黄レシチンを膜構成成分とするリポソームの調製
β−シトステロールをコレステロールに代えた以外は実施例1と同様にしてリポソーム組成物を得た。
リポソーム組成物によるB16BL6メラノーマ細胞の転移抑制作用
5週齢のC57BL6/Jマウス20匹を4群に分けた。コントロール群には1日1回0.2mLのリン酸緩衝生理食塩水(PBS)を飼育6日目まで強制的に経口投与した。同様に、リポソーム化β−シトステロール群にはPBSに代えて実施例1のリポソーム組成物を経口投与し、β−シトステロール群にはPBSに代えてリポソーム化されていない通常のβ−シトステロールの水懸濁液(リポソーム化β−シトステロール群に投与されたリポソーム化β−シトステロールと同重量のβ−シトステロールを含有する)を経口投与し、リポソーム化コレステロール群にはPBSに代えて比較例1のリポソーム組成物を経口投与した。飼育7日目に無血清培地に懸濁したB16BL6メラノーマ細胞(3×104個/0.2mL/匹)を静脈内投与した。飼育21日目にマウスを解剖して肺を摘出し、肺表面を観察してコロニーの数を数えた。各群マウスのコロニー数の平均値を表1に示す。
リポソーム組成物によるNK細胞に対する作用
5週齢のC57BL6/Jマウス3匹を3群に分けた。コントロール群には1日1回0.2mLのリン酸緩衝生理食塩水(PBS)を飼育6日目まで強制的に経口投与した。同様に、フィトステロール群にはPBSに代えて実施例1のリポソーム組成物を投与し、コレステロール群にはPBSに代えて比較例1のリポソーム組成物を経口投与した。飼育7日目にマウスを解剖して無菌状態で脾臓を摘出し、単一の脾臓細胞懸濁液を作成した。YAC-1細胞(ターゲット細胞)をNa2 51CrO4で標識した(3.7MBq/106個)。96ウェルタイタープレートに100μLの標識されたYAC-1細胞(1×104/well)を入れ、このウェルに脾臓細胞(エフェクター細胞、NK細胞)とYAC-1細胞の比(E/T比)が50:1、25:1となるように100μLのNK細胞を加えた(NK細胞添加ウェル)。また、NK細胞を加えないウェル(NK細胞非添加ウェル)も用意した。さらに、NK細胞添加ウェルと同じ細胞種、細胞量及び細胞比であるウェルにトリトンX-100を添加した(トリトン添加ウェル)。このプレートを5%CO2雰囲気中37℃で4時間インキュベートした後、200gで5分間遠心分離した。遠心分離により得られた上清において遊離された放射能をガンマカウンターで計測した。51Crの遊離比(NK活性)は下記の式で算出した。
卵黄レシチンとフィトステロールを用いてリポソームを調製し、該リポソームとその他の成分を用い、常法により下記の組成の錠剤を製造した。
Claims (11)
- フィトステロールを含んだリポソームを含有する抗癌用経口組成物。
- フィトステロールが、β−シトステロール、カンペステロール、スティグマステロール、ブラシカステロール、エルゴステロール及びエルゴスタディエノールからなる群から選択される少なくとも1種である請求項1に記載の経口組成物。
- リポソームにおけるフィトステロール含有量が1〜33重量%である請求項1に記載の経口組成物。
- 抗癌作用が癌転移抑制である請求項1〜3のいずれかに記載の経口組成物。
- 経口組成物が食品組成物である請求項1〜4のいずれかに記載の組成物。
- 経口組成物が医薬組成物である請求項1〜4のいずれかに記載の経口組成物。
- フィトステロールを含んだリポソームの癌転移抑制に有効な量を対象者に経口投与することを特徴とする癌を予防又は治療する方法。
- フィトステロールが、β−シトステロール、カンペステロール、スティグマステロール、ブラシカステロール、エルゴステロール及びエルゴスタディエノールからなる群から選択される少なくとも1種である請求項7に記載の癌を予防又は治療する方法。
- 経口投与されるリポソームの量が、成人一人1日あたり、10mg〜10000mgである請求項7又は8に記載の癌を予防又は治療する方法。
- 癌を予防又は治療するための、フィトステロールを含んだリポソームの使用。
- フィトステロールが、β−シトステロール、カンペステロール、スティグマステロール、ブラシカステロール、エルゴステロール及びエルゴスタディエノールからなる群から選択される少なくとも1種である請求項10に記載の使用。
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US20160101124A1 (en) * | 2014-10-13 | 2016-04-14 | King Abdullah International Medical Research Center | Nano-liposomal aminoglycoside-thymoquinone formulations |
CN104644761B (zh) * | 2015-03-18 | 2018-05-25 | 甘肃指南针生物工程中心(特殊普通合伙企业) | 肉苁蓉麦角甾醇肠溶微丸 |
CN105769878B (zh) * | 2016-03-11 | 2018-08-10 | 浙江中医药大学 | 一种麦角甾醇的用途及其制备的麦角甾醇脂质体 |
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EP3560516A1 (en) * | 2018-04-27 | 2019-10-30 | Bergen Teknologioverforing AS | Combination therapy including beta-sitosterol in combination with at least one of a braf inhibitor, a mek inhibitor or an erk inhibitor and methods and use thereof |
JP2019202954A (ja) * | 2018-05-23 | 2019-11-28 | 株式会社らいむ | 神経形成促進剤、内服剤、培地用添加剤、細胞希釈液用添加剤、培地および細胞希釈液 |
WO2022125794A1 (en) * | 2020-12-11 | 2022-06-16 | PPC Pharmaceuticals, LLC | Composition and delivery system for immune system support |
CN112869165A (zh) * | 2021-01-27 | 2021-06-01 | 广州中国科学院先进技术研究所 | 一种植物甾醇纳米脂质体的制备方法 |
CN113967192A (zh) * | 2021-11-09 | 2022-01-25 | 陕西海斯夫生物工程有限公司 | 一种用于加速伤口愈合的药物组合物、它们的制备方法与用途 |
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