JP2012509284A - 中枢神経系への対流増進送達のためのリポソーム組成物 - Google Patents
中枢神経系への対流増進送達のためのリポソーム組成物 Download PDFInfo
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Abstract
Description
F2:DSPC/DSPG/CHOL 0.3 DL比 Ls−TPT0.5mg/mL+Ls−GD1.15mg/mL
F3:DSPC/DSPG/CHOL0.1 DL比 Ls−TPT 0.5mg/mL+Ls−GD1.15mg/mL
F4:遊離トポテカン0.5mg/mL
DSPC/DSPG=ジステアロイルホスファチジルコリン/ジステアロイルホスファチジルグリセロール
Chol=コレステロール
DL比=薬物脂質比(w/w)
Ls−TPT=リポソームトポテカン
Ls−GD=リポソームガドジアミド
F2:DSPC/DSPG/CHOL 0.3 D:L比 Ls−TPT0.5mg/mL+Ls−GD 1.15mg/mL
F3: DSPC/DSPG/CHOL 0.1 D:L比 Ls−TPT0.5mg/mL+Ls−GD 1.15mg/mL
F4:遊離トポテカン0.5mg/mL
DSPC/DSPG=ジステアロイルホスファチジルコリン/ジステロイルホスファチジルグリセロール
Chol=コレステロール
D:L比=薬物脂質比(w/w)
Ls−TPT=リポソームトポテカン
Ls−GD=リポソームガドジアミド
( )は、交換された動物の数を示す
F2:DSPC/DSPG/CHOL 0.3 D:L比 Ls−TPT0.5mg/mL+Ls−GD 1.15mg/mL
F3:DSPC/DSPG/CHOL 0.1 D:L比 Ls−TPT0.5mg/mL+Ls−GD 1.15mg/mL
F4:遊離トポテカン0.5mg/mL
DSPC/DSPG=ジステアロイルホスファチジルコリン/ジステロイルホスファチジルグリセロール
CHOL=コレステロール
D:L比=薬物:脂質比(w/w)
Ls−TPT=リポソームトポテカン
Ls−GD=リポソームガドジアミド
第2群:無処置脳組織−DSPC/DSPG/CHOL D:L0.3+Ls−TPT1.02mg/mL+Ls−GD1.15mg/mL
第3群:腫瘍組織−DSPC/DSPG/CHOL D:L0.1+Ls−TPT0.38mg/mL+Ls−GD1.15mg/mL
第4群:腫瘍組織−DSPC/DSPG/CHOL D:L0.3+Ls−TPT1.02mg/mL+Ls−GD1.15mg/mL
DSPC/DSPG=ジステアロイルホスファチジルコリン/ジステアロイルホスファチジルグリセロール
CHOL=コレステロール
D:L比=薬物:脂質比(w/w)
Ls−TPT=リポソームトポテカン
Ls−GD=リポソームガドジアミド
第1群:無処置脳組織−DSPC/DSPG/CHOL D:L 0.1+Ls−TPT 0.38mg/mL+Ls−GD 1.15mg/mL
第2群:無処置脳組織−DSPC/DSPG/CHOL D:L 0.3+Ls−TPT 1.02mg/mL+Ls−GD 1.15mg/mL
1.Stupp R, Mason WP, van den Bent MJ et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma N Engl J Med 352:987−996, 2005
2.Bobo RH, Laske DW, Akbasak A, et al. Convection−enhanCED delivery of macromolecules in the brain Proc Natl Acad Sci USA 91:2076−2080, 1994
3.Lieberman DM, Laske DW, Morrison PF, et al. Convection−enhanCED distribution of large molecules in gray matter during interstitial drug infusion J Neurosurg 82:1021−1029, 1995
4.Morrison PF, Laske DW, Bobo H, et al. High−flow microinfusion: tissue penetration and pharmacodynamics Am J Physiol 266:R292−305, 1994
5.Croteau D, Walbridge S, Morrison PF, Butman JA, Vortmeyer AO et al. Real−time in vivo imaging of the convective distribution of a low−molecular−weight tracer J Neurosurg 102:90−97, 2005
6.Lonser RR, Walbridge S, Garmestani K, Butman JA, Walters HA et al. Succesful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion J Neurosurg 97:905−913, 2002
7.Sampson JH, Brady ML, Petry NA, Croteau, D, Friedman AH et al. Intracerebral mfusate distribution by convection−enhanCED delivery in humans with malignant gliomas descriptive effects of target anatomy and catheter positioning Neurosurgery 60 [ONS Suppl 1]:89−98, 2007
8.Moog R, Burger AM, Brandl M et al. Change in pharmacokinetics and pharmacodynamic behavior of gemcitabine in human tumor xenografts upon entrapment in vesicular phospholipid gels Cancer Chemother Pharmacol 49:356−366, 2002
9.Saito R, Krauze MT, Noble CO, Drummond DC, Kirpotin DB et al. Convection− enhanCED delivery of Ls−TPT enables an effective, continous, low−dose chemotherapy against malignant glioma xenograft model. Neuro−Oncol 8:205−214, 2006
10.Schmidt F, Rieger J, Wischhusen J, Naumann U, Weller M. Glioma cell sensitivity to topotecan: the role of p53 and topotecan−induCED DNA damage. Eur J Pharmacology 412:21−25, 2001
11.Kaiser MG, Parsa AT, Fine RL, Hall JS, Chakrabarti I et al. Tissue distribution and antitumor activity of topotecan delivered by intracerebral clysis in a rat glioma model. Neurosurg 47: 1391−1398, 2000
12.Pollina J, Plunkett RJ, Ciesielski MJ, LIs A, Barone TA et al. lntratumoral infusion of topotecan prolongs survival in the nude rat intracranial U87 human glioma model. J Neuro− Onc 39:217−225, 1998
13.Lonser RR, Schiffman R, Robison RA, Butman JA, Quezado J et al. Image−guided, direct convective delivery of glucocerebrosidase for neuronopathic Gaucher disease. Neurology 68:254−261 , 2007
14.Murad GJ, Walbridge S, Morrison PF, Garmestani K, Degen JW et al. Real−time, image−guided, convection−enhanCED delivery of interleukin 13 bound to pseudomonas exotoxin. Clin Cancer Res 12(10):3145−3151, 2006
15.Saito R, Bringas JR, McKnight TR, Wendland MF, Mamot C et al. Distribution of liposomes into brain and rat brain tumor models by convection−enhanCED delivery monitored with magnetic resonance imaging. Cancer Res 64:2572−79, 2004
16.Saito R, Krauze MT, Bringas JR, Noble C, McKnight TR et al. Gadolinium−loaded liposomes allow for real−time magnetic resonance imaging of convection−enhanCED delivery in the primate brain. Exp Neurol 196(2):381−389, 2005
Claims (20)
- 対流増進送達を介して中枢神経系に薬学的薬剤を投与するための改良された非ペグ化リポソーム送達媒体であって、少なくとも1種の飽和中性リン脂質および少なくとも1種の飽和陰イオンリン脂質を含む、リポソーム製剤に被包された治療または診断薬剤を含む、媒体。
- 前記媒体は、少なくとも1種の飽和中性リン脂質および少なくとも1種の飽和陰イオンリン脂質から本質的に成る、請求項1に記載の非ペグ化リポソーム送達媒体。
- ステロールをさらに含む、請求項1に記載の非ペグ化リポソーム送達媒体。
- 前記リポソーム製剤は、DSPC、DSPG、およびCHOLを含むか、またはそれらから本質的に成る、請求項3に記載の非ペグ化リポソーム送達媒体。
- 前記リポソーム送達媒体は、7:2:1のモル比のDSPC、DSPG、およびCHOLから本質的に成る、請求項4に記載の非ペグ化リポソーム送達媒体。
- 前記リポソーム送達媒体は、トポイソメラーゼ阻害剤を被包する、請求項1〜5のいずれか1項に記載の非ペグ化リポソーム送達媒体を含む、治療用組成物。
- 前記トポイソメラーゼ阻害剤は、トポテカンである、請求項6に記載の治療用組成物。
- 前記トポイソメラーゼ阻害剤は、少なくとも約500μg/mLの初期薬物濃度で存在する、請求項6に記載の治療用組成物。
- 前記リポソーム送達媒体は、毒素を被包する、請求項1〜5のいずれか1項に記載の非ペグ化リポソーム送達媒体を含む、治療用組成物。
- 前記毒素は、ω−コノトキシン、ボツリヌス毒素、μ−コノトキシン、およびα−コナントキンペプチドから成る群から選択される、請求項9に記載の治療用組成物。
- 前記タンパク質毒素は、コノトキシンである、請求項10に記載の治療用組成物。
- CNS障害を治療する改良された方法であって、それを必要とする患者に、請求項1〜5のいずれか1項に記載のリポソーム送達媒体、または請求項6〜11のいずれか1項に記載の治療用組成物を投与することを含む、方法。
- 前記CNS障害は、CNS腫瘍であり、前記治療薬剤は、トポイソメラーゼ阻害剤である、請求項12に記載の方法。
- 前記CNS障害は、てんかんであり、前記治療薬剤は、毒素である、請求項12に記載の方法。
- 前記毒素は、コノトキシンである、請求項14に記載の方法。
- 飽和中性リン脂質および飽和陰イオンリン脂質を含むか、またはそれらから本質的に成るリポソームに被包された少なくとも1種の診断薬剤を共投与することをさらに含む、請求項12に記載の方法。
- CNS腫瘍の治療を必要としている患者において使用するための、請求項6〜8のいずれか1項に記載の治療用組成物。
- てんかんの治療を必要としている患者において使用するための、請求項9〜11のいずれか1項に記載の治療用組成物。
- 前記リポソーム送達媒体は、MRI磁石を被包する、請求項1〜5のいずれか1項に記載の非ペグ化リポソーム送達媒体を含む、診断用組成物。
- 前記MRI磁石は、ガドジアミドおよびローダミンから成る群から選択される、請求項19に記載の診断用組成物。
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GB201204263D0 (en) * | 2012-03-12 | 2012-04-25 | Renishaw Plc | Giloma treatment |
EP2908909A1 (en) * | 2012-10-19 | 2015-08-26 | The Regents Of The University Of California | Treating tumors of the central nervous system |
US9993427B2 (en) * | 2013-03-14 | 2018-06-12 | Biorest Ltd. | Liposome formulation and manufacture |
AU2016206478A1 (en) | 2015-01-16 | 2017-06-15 | Voyager Therapeutics, Inc. | Central nervous system targeting polynucleotides |
US20170049701A1 (en) * | 2015-08-05 | 2017-02-23 | Steven M. Kushner | Clustoidal multilamellar soy lecithin phospholipid structures for transdermal, transmucosal, or oral delivery, improved intestinal absorption, and improved bioavailability of nutrients |
CN109069817B (zh) | 2016-04-15 | 2021-07-13 | 富士胶片株式会社 | 微针阵列 |
EP3603620A4 (en) * | 2017-03-31 | 2020-03-25 | FUJIFILM Corporation | LIPOSOME COMPOSITION AND PHARMACEUTICAL COMPOSITION |
US10722465B1 (en) * | 2017-12-08 | 2020-07-28 | Quicksilber Scientific, Inc. | Transparent colloidal vitamin supplement |
WO2019222441A1 (en) | 2018-05-16 | 2019-11-21 | Voyager Therapeutics, Inc. | Aav serotypes for brain specific payload delivery |
US11291702B1 (en) | 2019-04-15 | 2022-04-05 | Quicksilver Scientific, Inc. | Liver activation nanoemulsion, solid binding composition, and toxin excretion enhancement method |
WO2020231700A1 (en) * | 2019-05-11 | 2020-11-19 | Youngsuk Yi | Neurotoxin compositions and methods |
CN114469863B (zh) * | 2021-11-26 | 2023-09-26 | 南方医科大学南方医院 | 甾醇脂质体作为牙髓和牙本质药物传递系统的应用 |
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BRPI0922100A2 (pt) | 2016-02-10 |
EP2370058B1 (en) | 2017-10-18 |
CN102256596A (zh) | 2011-11-23 |
CN102256596B (zh) | 2014-10-22 |
CA2743959A1 (en) | 2010-05-27 |
AR076634A1 (es) | 2011-06-29 |
EP2370058A1 (en) | 2011-10-05 |
JP5795537B2 (ja) | 2015-10-14 |
US20110274625A1 (en) | 2011-11-10 |
AU2009317837A1 (en) | 2011-06-30 |
CA2743959C (en) | 2017-09-26 |
AU2009317837B2 (en) | 2016-02-25 |
WO2010057317A1 (en) | 2010-05-27 |
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