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1.
公开(公告)号:US20120225434A1
公开(公告)日:2012-09-06
申请号:US13460963
申请日:2012-05-01
申请人: Marco A. CIUFOLINI , Thomas D. Madden , Michael J. Hope , Barbara Mui , Antonin de Fougerolles , Tatiana Novobrantseva , Anna Borodovsky , Akin Akinc , Mark Tracy , Pieter Rutter Cullis
发明人: Marco A. CIUFOLINI , Thomas D. Madden , Michael J. Hope , Barbara Mui , Antonin de Fougerolles , Tatiana Novobrantseva , Anna Borodovsky , Akin Akinc , Mark Tracy , Pieter Rutter Cullis
CPC分类号: G01N33/5088 , A01K2207/05 , A01K2227/105 , A01K2267/0381 , C12N15/111 , C12N15/1137 , C12N2310/14 , C12N2320/10 , C12Q1/6876 , C12Q2600/136 , C12Q2600/158 , C12Q2600/178 , C12Y304/21021 , G01N33/5023 , G01N33/5067 , G01N33/86 , G01N2333/745 , G01N2333/96447
摘要: The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-Dilinoley 1-4-dimethylaminomethyl-[1,3]-dioxolane by screening for an effect of the agent on the liver of a model subject.
摘要翻译: 本发明的特征在于通过筛选试剂对模型受试者的肝脏的影响来鉴定治疗相关组合物的方法,所述组合物包括治疗剂和2,2-二苯胺基-4-二甲基氨基甲基 - [1,3] - 二氧杂环戊烷。
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2.
公开(公告)号:US20110097720A1
公开(公告)日:2011-04-28
申请号:US12811503
申请日:2008-12-31
申请人: Marco A. Ciufolini , Thomas D. Madden , Michael J. Hope , Barbara Mui , De Fougerolles Antonin , Tatiana Novobrantseva , Anna Borodovsky , Akin Akinc , Mark Tracy , Pieter Rutter Cullis
发明人: Marco A. Ciufolini , Thomas D. Madden , Michael J. Hope , Barbara Mui , De Fougerolles Antonin , Tatiana Novobrantseva , Anna Borodovsky , Akin Akinc , Mark Tracy , Pieter Rutter Cullis
CPC分类号: G01N33/5088 , A01K2207/05 , A01K2227/105 , A01K2267/0381 , C12N15/111 , C12N15/1137 , C12N2310/14 , C12N2320/10 , C12Q1/6876 , C12Q2600/136 , C12Q2600/158 , C12Q2600/178 , C12Y304/21021 , G01N33/5023 , G01N33/5067 , G01N33/86 , G01N2333/745 , G01N2333/96447
摘要: The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-Dilinoley 1-4-dimethylaminomethyl-[1,3]-dioxolane by screening for an effect of the agent on the liver of a model subject.
摘要翻译: 本发明的特征在于通过筛选试剂对模型受试者的肝脏的影响来鉴定治疗相关组合物的方法,所述组合物包括治疗剂和2,2-二苯胺基-4-二甲基氨基甲基 - [1,3] - 二氧杂环戊烷。
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公开(公告)号:US20110117125A1
公开(公告)日:2011-05-19
申请号:US12811195
申请日:2008-12-31
申请人: Michael J. Hope , Sean C. Semple , Jianxin Chen , Thomas D. Madden , Barbara Mui , Pieter R. Cullis , Marco A. Ciufolini , Kim F. Wong , Muthiah Manoharan , Rajeev G. Kallanthottathil
发明人: Michael J. Hope , Sean C. Semple , Jianxin Chen , Thomas D. Madden , Barbara Mui , Pieter R. Cullis , Marco A. Ciufolini , Kim F. Wong , Muthiah Manoharan , Rajeev G. Kallanthottathil
IPC分类号: A61K39/12 , A61K39/00 , A61K39/02 , C12N5/02 , A61K31/7088 , A61P37/00 , C07D295/12 , C07D241/04 , C07D317/00 , C11C3/00 , C07C229/00 , C07C229/30 , C07C321/00
CPC分类号: A61K31/7088 , A61K9/127 , A61K9/1275 , C07C215/10 , C07C217/08 , C07C217/28 , C07C219/08 , C07C229/12 , C07C271/12 , C07C323/25 , C07D317/28
摘要: The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
摘要翻译: 本发明提供了将治疗剂递送至细胞的组合物和方法。 特别地,这些包括提供核酸的有效包封的新型脂质和核酸 - 脂质颗粒,并将包封的核酸有效地递送到细胞体内。 本发明的组合物是高度有效的,从而允许以相对低的剂量有效击倒特异性靶蛋白。 此外,与本领域已知的组合物和方法相比,本发明的组合物和方法毒性低,并提供更大的治疗指数。
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公开(公告)号:US20110256175A1
公开(公告)日:2011-10-20
申请号:US13123307
申请日:2009-10-09
申请人: Michael J. Hope , Sean C. Semple , Jianxin Chen , Thomas D. Madden , Pieter R. Cullis , Marco A. Ciufolini , Barbara Low Shoud Mui
发明人: Michael J. Hope , Sean C. Semple , Jianxin Chen , Thomas D. Madden , Pieter R. Cullis , Marco A. Ciufolini , Barbara Low Shoud Mui
IPC分类号: A61K39/12 , C07D319/06 , C07D405/06 , C07D413/06 , A61K47/44 , A61K31/7088 , A61K48/00 , A61K31/713 , C12N5/071 , C12N15/63 , A61K39/02 , A61K39/00 , A61P37/04 , A61P35/00 , A61P31/12 , A61P31/04 , A61P33/00 , C07D317/28
CPC分类号: A61K47/22 , A61K9/1271 , A61K31/713 , A61K39/39 , A61K2039/55511 , C07D317/28 , C07D319/06
摘要: The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
摘要翻译: 本发明提供优异的用于将治疗剂递送至细胞的组合物和方法。 特别地,这些包括提供核酸的有效包封的新型脂质和核酸 - 脂质颗粒,并将包封的核酸有效地递送到细胞体内。 本发明的组合物是高度有效的,从而允许在相对低的剂量下有效击倒特异性靶蛋白。 此外,与本领域已知的组合物和方法相比,本发明的组合物和方法毒性低,并提供更大的治疗指数。
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公开(公告)号:US09139554B2
公开(公告)日:2015-09-22
申请号:US13123307
申请日:2009-10-09
申请人: Michael J. Hope , Sean C. Semple , Jianxin Chen , Thomas D. Madden , Pieter R. Cullis , Marco A. Ciufolini , Barbara Low Shoud Mui
发明人: Michael J. Hope , Sean C. Semple , Jianxin Chen , Thomas D. Madden , Pieter R. Cullis , Marco A. Ciufolini , Barbara Low Shoud Mui
IPC分类号: C07D317/28 , A61K9/127 , C07D319/06
CPC分类号: A61K47/22 , A61K9/1271 , A61K31/713 , A61K39/39 , A61K2039/55511 , C07D317/28 , C07D319/06
摘要: The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.
摘要翻译: 本发明提供优异的用于将治疗剂递送至细胞的组合物和方法。 特别地,这些包括提供核酸的有效包封的新型脂质和核酸 - 脂质颗粒,并将包封的核酸有效地递送到细胞体内。 本发明的组合物是高度有效的,从而允许在相对低的剂量下有效击倒特异性靶蛋白。 此外,与本领域已知的组合物和方法相比,本发明的组合物和方法毒性低,并提供更大的治疗指数。
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6.
公开(公告)号:US20090285878A1
公开(公告)日:2009-11-19
申请号:US11667138
申请日:2005-11-04
申请人: Michael J. Hope , Barbara Mui , Thomas D. Madden
发明人: Michael J. Hope , Barbara Mui , Thomas D. Madden
IPC分类号: A61K31/4745 , A61K9/127 , A61P35/00
CPC分类号: A61K31/4745 , A61K9/127 , A61K31/47
摘要: The present invention is directed to liposomal compositions comprising a camptothecin, which are optimized to reduce camptothecin degradation and/or precipitation of camptothecin degradation products in the external medium. The invention further provides improved methods of formulating liposomal camptothecins, kits comprising liposome-encapsulated camptothecins, and methods of using the same to treat a variety of diseases and disorders, including cancer.
摘要翻译: 本发明涉及包含喜树碱的脂质体组合物,其被优化以减少喜树碱降解和/或在外部介质中降解喜树碱降解产物。 本发明进一步提供了制备脂质体喜树碱的改进方法,包含脂质体包封的喜树碱的试剂盒,及其使用方法来治疗各种疾病和病症,包括癌症。
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公开(公告)号:US5837279A
公开(公告)日:1998-11-17
申请号:US450831
申请日:1995-05-25
申请人: Andrew S. Janoff , Pieter R. Cullis , Marcel B. Bally , Michael W. Fountain , Richard S. Ginsberg , Michael J. Hope , Thomas D. Madden , Hugh P. Schieren , Regina L. Jablonski
发明人: Andrew S. Janoff , Pieter R. Cullis , Marcel B. Bally , Michael W. Fountain , Richard S. Ginsberg , Michael J. Hope , Thomas D. Madden , Hugh P. Schieren , Regina L. Jablonski
IPC分类号: C07D475/08 , A61K9/00 , A61K9/10 , A61K9/127 , A61K31/435 , A61K31/505 , A61K31/519 , A61K31/70 , A61K31/7028 , A61K31/7034 , A61K31/704 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61K31/7068 , A61K31/715 , A61K45/00 , A61K45/08 , A61K47/26 , A61K47/36 , A61K47/48 , A61P35/00 , B01J13/02 , B01J13/04 , C07D519/00 , C07H15/252 , C07H19/09
CPC分类号: A61K9/1277 , A61K9/1271 , A61K9/1278
摘要: Dehydrated liposomes are prepared by drying liposome preparations under reduced pressure in the presence of one or more protective sugars, e.g., the disaccharides trehalose and sucrose. Preferably, the protective sugars are present at both the inside and outside surfaces of the liposome membranes. Freezing of the liposome preparation prior to dehydration is optional. Alternatively, the protective sugar can be omitted if: (1) the liposomes are of the type which have multiple lipid layers; (2) the dehydration is done without prior freezing; and (3) the dehydration is performed to an end point which results in sufficient water being left in the preparation (e.g., at least 12 moles water/mole lipid) so that the integrity of a substantial portion of the multiple lipid layers is retained upon rehydration. Concentration gradients capable of generating transmembrane potentials can be created across the liposome membranes either before or after dehydration, and the transmembrane potentials resulting from these gradients can be used to load charged materials, e.g., drugs, into the liposomes.
摘要翻译: 通过在一种或多种保护性糖例如二糖类海藻糖和蔗糖的存在下,减压干燥脂质体制剂来制备脱水脂质体。 优选地,保护性糖存在于脂质体膜的内表面和外表面。 在脱水之前冻干脂质体制剂是任选的。 或者,如果:(1)脂质体是具有多个脂质层的类型,则可以省略保护性糖; (2)脱水是在没有预先冻结的情况下进行的; 和(3)脱水进行到终点,导致制剂中留有足够的水(例如,至少12摩尔水/摩尔脂质),使得大部分多脂质层的完整性保持在 补液。 可以在脱水之前或之后在脂质体膜上产生能够产生跨膜电位的浓度梯度,并且由这些梯度产生的跨膜电位可用于将带电材料(例如药物)加载到脂质体中。
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公开(公告)号:US5736155A
公开(公告)日:1998-04-07
申请号:US461212
申请日:1995-06-05
CPC分类号: A61K9/1278 , A61K9/1271 , A61K9/1277
摘要: Methods for encapsulating ionizable antineoplastic agents in liposomes using transmembrane potentials are provided. Trapping efficiencies approaching 100% and rapid loading are readily achieved. Dehydration protocols which allow liposomes to be conveniently used in the administration of antineoplastic agents in a clinical setting are also provided. In accordance with other aspects of the invention, transmembrane potentials are used to reduce the rate of release of ionizable drugs from liposomes.
摘要翻译: 提供了使用跨膜电位将可电离抗肿瘤剂包封在脂质体中的方法。 捕获效率接近100%,快速加载容易实现。 还提供允许脂质体在临床环境中方便地用于施用抗肿瘤剂的脱水方案。 根据本发明的其他方面,使用跨膜电位来降低可离子化药物从脂质体释放的速率。
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公开(公告)号:US5922350A
公开(公告)日:1999-07-13
申请号:US876938
申请日:1997-06-16
申请人: Andrew S. Janoff , Pieter R. Cullis , Marcel B. Bally , Michael W. Fountain , Richard S. Ginsberg , Michael J. Hope , Thomas D. Madden , Hugh P. Schieren , Regina L. Jablonski
发明人: Andrew S. Janoff , Pieter R. Cullis , Marcel B. Bally , Michael W. Fountain , Richard S. Ginsberg , Michael J. Hope , Thomas D. Madden , Hugh P. Schieren , Regina L. Jablonski
IPC分类号: C07D475/08 , A61K9/00 , A61K9/10 , A61K9/127 , A61K31/435 , A61K31/505 , A61K31/519 , A61K31/70 , A61K31/7028 , A61K31/7034 , A61K31/704 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61K31/7068 , A61K31/715 , A61K45/00 , A61K45/08 , A61K47/26 , A61K47/36 , A61K47/48 , A61P35/00 , B01J13/02 , B01J13/04 , C07D519/00 , C07H15/252 , C07H19/09
CPC分类号: A61K9/1277 , A61K9/1271 , A61K9/1278
摘要: Dehydrated liposomes are prepared by drying liposome preparations under reduced pressure in the presence of one or more protective sugars, e.g., the disaccharides trehalose and sucrose. Preferably, the protective sugars are present at both the inside and outside surfaces of the liposome membranes. Freezing of the liposome preparation prior to dehydration is optional. Alternatively, the protective sugar can be omitted if: (1) the liposomes are of the type which have multiple lipid layers; (2) the dehydration is done without prior freezing; and (3) the dehydration is performed to an end point which results in sufficient water being left in the preparation (e.g., at least 12 moles water/mole lipid) so that the integrity of a substantial portion of the multiple lipid layers is retained upon rehydration. Concentration gradients capable of generating transmembrane potentials can be created across the liposome membranes either before or after dehydration, and the transmembrane potentials resulting from these gradients can be used to load charged materials, e.g., drugs, into the liposomes.
摘要翻译: 通过在一种或多种保护性糖例如二糖类海藻糖和蔗糖的存在下,减压干燥脂质体制剂来制备脱水脂质体。 优选地,保护性糖存在于脂质体膜的内表面和外表面。 在脱水之前冻干脂质体制剂是任选的。 或者,如果:(1)脂质体是具有多个脂质层的类型,则可以省略保护性糖; (2)脱水是在没有预先冻结的情况下进行的; 和(3)脱水进行到终点,导致制剂中留有足够的水(例如,至少12摩尔水/摩尔脂质),使得大部分多脂质层的完整性保持在 补液。 可以在脱水之前或之后在脂质体膜上产生能够产生跨膜电位的浓度梯度,并且由这些梯度产生的跨膜电位可用于将带电材料(例如药物)加载到脂质体中。
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公开(公告)号:US5077056A
公开(公告)日:1991-12-31
申请号:US284751
申请日:1988-12-12
IPC分类号: A61K9/127
CPC分类号: A61K9/1278 , A61K9/1277 , Y10S436/829
摘要: Methods for encapsulating ionizable antineoplastic agents in liposomes using transmembrane potentials are provided. Trapping efficiencies approaching 100% and rapid loading are readily achieved. Dehydration protocols which allow liposomes to be conveniently used in the administration of antineoplastic agents in a clinical setting are also provided. In accordance with other aspects of the invention, transmembrane potentials are used to reduce the rate of release of ionizable drugs from liposomes.
摘要翻译: 提供了使用跨膜电位将可电离抗肿瘤剂包封在脂质体中的方法。 捕获效率接近100%,快速加载容易实现。 还提供允许脂质体在临床环境中方便地用于施用抗肿瘤剂的脱水方案。 根据本发明的其他方面,使用跨膜电位来降低可离子化药物从脂质体释放的速率。
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