公开(公告)号：US20100041152A1

公开(公告)日：2010-02-18

申请号：US12404837

申请日：2009-03-16

申请人： Jeffery J. Wheeler ,  Michael J. Hope ,  Pieter R. Cullis ,  Marcel B. Bally

发明人： Jeffery J. Wheeler ,  Michael J. Hope ,  Pieter R. Cullis ,  Marcel B. Bally

IPC分类号： C12N15/88 ,  C12N15/63

CPC分类号： C12N15/88 ,  A61K9/1272 ,  Y10S436/829 ,  Y10S514/851 ,  Y10S977/80 ,  Y10S977/907

摘要： Plasmid-lipid particles which are useful for transfection of cells in vitro or in vivo are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. The particles are typically 65-85 nm, fully encapsulate the plasmid and are serum-stable.

摘要翻译： 描述了可用于体外或体内转染细胞的质粒 - 脂质颗粒。 可以使用洗涤剂透析方法或利用有机溶剂的方法形成颗粒。 颗粒通常为65-85nm，完全包封质粒并且是血清稳定的。

公开(公告)号：US06858225B2

公开(公告)日：2005-02-22

申请号：US09895480

申请日：2001-06-29

申请人： Sean C. Semple ,  Sandra K. Klimuk ,  Troy Harasym ,  Michael J. Hope ,  Steven M. Ansell ,  Pieter Cullis ,  Peter Scherrer ,  Dan Debeyer

发明人： Sean C. Semple ,  Sandra K. Klimuk ,  Troy Harasym ,  Michael J. Hope ,  Steven M. Ansell ,  Pieter Cullis ,  Peter Scherrer ,  Dan Debeyer

IPC分类号： A61K9/127 ,  A61K9/50 ,  A61K31/7105 ,  A61K31/711 ,  A61K47/28 ,  A61K47/44 ,  A61K48/00 ,  A61K31/70 ,  C07H21/00 ,  C12N11/02 ,  C12N15/88

CPC分类号： A61K9/1277 ,  A61K9/1272 ,  Y10T428/2984

摘要： Methods for the preparation of a lipid-nucleic acid composition are provided. According to the methods, a mixture of lipids containing a protonatable or deprotonatable lipid, for example an amino lipid and a lipid such as a PEG- or Polyamide oligomer-modified lipid is combined with a buffered aqueous solution of a charged therapeutic agent, for example polyanionic nucleic acids, to produce particles in which the therapeutic agent is encapsulated in a lipid vesicle. Surface charges on the lipid particles are at least partially neutralized to provide surface-neutralized lipid-encapsulated compositions of the therapeutic agents. The method permits the preparation of compositions with high ratios of therapeutic agent to lipid and with encapsulation efficiencies in excess of 50%.

摘要翻译： 提供了制备脂质 - 核酸组合物的方法。 根据该方法，将包含可质子化或不可质令排泄的脂质，例如氨基脂质和脂质如PEG-或聚酰胺低聚物修饰的脂质的脂质混合物与带电疗法的缓冲水溶液组合，例如 聚阴离子核酸，以产生其中治疗剂包封在脂质囊泡中的颗粒。 脂质颗粒上的表面电荷至少部分被中和，以提供治疗剂的表面中和的脂质包封的组合物。 该方法允许制备具有高比例的治疗剂与脂质并且包封效率超过50％的组合物。

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。

公开(公告)号：US5204112A

公开(公告)日：1993-04-20

申请号：US61837

申请日：1987-06-12

申请人： Michael J. Hope ,  Pieter R. Cullis

发明人： Michael J. Hope ,  Pieter R. Cullis

IPC分类号： A61K9/127 ,  A61K9/133

CPC分类号： A61K9/1277 ,  A61K9/1278 ,  Y10S436/829 ,  Y10T428/2984

摘要： Methods are described for controlling the transbilayer distribution of ionizable lipids and proteins in vesicles. Control of the ion gradient of the exterior bathing medium in relation to that of the interior entrapped aqueous compartment of the vesicles induces migration of ionizable lipids or proteins to one or the other of the monolayers comprising the bilayer. This can result in an asymmetric distribution of the ionizable lipid or ionizable protein. The basic ionizable lipids, such as stearylamine and sphingosine, are sequestered into the inner monolayer when the liposome interior is acidic relative to the liposome exterior. Conversely, acidic ionizable lipids such as oleic acid and stearic acid are sequestered into the inner monolayer when the liposome interior is basic relative to the liposome exterior bathing solution. Likewise, phospholipids such as phosphatidylglycerol, phosphatidylinositol, and cardiolipin may also be sequestered into the inner monolayer in response to a relatively acidic exterior medium. Such vesicles may contain bioactive agents and may be administered to mammals including humans.

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。

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。

公开(公告)号：US07341738B2

公开(公告)日：2008-03-11

申请号：US10658947

申请日：2003-09-09

申请人： Sean C. Semple ,  Sandra K. Klimuk ,  Troy Harasym ,  Michael J. Hope ,  Steven M. Ansell ,  Pieter Cullis ,  Peter Scherrer ,  Dan Debeyer

发明人： Sean C. Semple ,  Sandra K. Klimuk ,  Troy Harasym ,  Michael J. Hope ,  Steven M. Ansell ,  Pieter Cullis ,  Peter Scherrer ,  Dan Debeyer

IPC分类号： A61K9/127 ,  A61K31/70 ,  C12N11/02 ,  C12N15/88 ,  C07H21/00

CPC分类号： A61K9/1277 ,  A61K9/1272 ,  Y10T428/2984

摘要： Methods for the preparation of a lipid-nucleic acid composition are provided. According to the methods, a mixture of lipids containing a protonatable or deprotonatable lipid, for example an amino lipid and a lipid such as a PEG- or Polyamide oligomer-modified lipid is combined with a buffered aqueous solution of a charged therapeutic agent, for example polyanionic nucleic acids, to produce particles in which the therapeutic agent is encapsulated in a lipid vesicle. Surface charges on the lipid particles are at least partially neutralized to provide surface-neutralized lipid-encapsulated compositions of the therapeutic agents. The method permits the preparation of compositions with high ratios of therapeutic agent to lipid and with encapsulation efficiencies in excess of 50%.

摘要翻译： 提供了制备脂质 - 核酸组合物的方法。 根据该方法，将包含可质子化或不可质令排泄的脂质，例如氨基脂质和脂质如PEG-或聚酰胺低聚物修饰的脂质的脂质混合物与带电疗法的缓冲水溶液组合，例如 聚阴离子核酸，以产生其中治疗剂包封在脂质囊泡中的颗粒。 脂质颗粒上的表面电荷至少部分被中和，以提供治疗剂的表面中和的脂质包封的组合物。 该方法允许制备具有高比例的治疗剂与脂质并且包封效率超过50％的组合物。

公开(公告)号：US07101570B2

公开(公告)日：2006-09-05

申请号：US09992107

申请日：2001-11-05

申请人： Michael J. Hope ,  Wendi Rodrigueza

发明人： Michael J. Hope ,  Wendi Rodrigueza

IPC分类号： A61K9/127 ,  A61K9/133

CPC分类号： A61K31/685 ,  A61K9/127 ,  Y10S514/824 ,  Y10T428/2984

摘要： The present invention provides compositions and methods for treating atherosclerosis. The compositions comprise unilamellar liposomes having an average diameter of 100-150 nanometers. Methods for treating atherosclerosis employing the compositions of the present invention are also provided.

公开(公告)号：US06461163B1

公开(公告)日：2002-10-08

申请号：US09735011

申请日：2000-12-12

申请人： Michael A. Gallagher ,  Michael J. Hope

发明人： Michael A. Gallagher ,  Michael J. Hope

IPC分类号： A63B6936

CPC分类号： A63B69/3638 ,  A63B15/005 ,  A63B60/04 ,  A63B69/0024 ,  A63B69/0026 ,  A63B69/3635 ,  A63B69/38 ,  A63B2069/0008 ,  A63B2102/22 ,  A63B2102/24

摘要： The present invention covers a swing trainer arrangement for providing recognizable signals to the user/holder of a sports club or racket to indicate the optimum swing and strike locations during playing with a ball or puck. The swing trainer arrangement comprises a first stopper and a second stopper each may be adjustably arranged to be supported at a selected location of a shaft or handle of the sports club or racket. At least one movable member is arranged to be slideably disposed between the first and second stoppers to generate a signal when they hit one another of a stopper as to indicate certain preferred arcuate swing locations of the shaft or handle during such play thereof, or indicate to the user as to inaccuracies of that swing when a sound is produced before or after the club swings through an optimum location for hitting a ball, puck or the like.

摘要翻译： 本发明涉及一种用于向运动俱乐部或球拍的用户/支架提供可识别信号的摆动训练器装置，以在玩球或圆球期间指示最佳摆动和击打位置。 摆动训练器装置包括第一止动器和第二止动件，每个止动器和第二止动件可以可调节地布置成被支撑在运动杆或球拍的轴或手柄的选定位置。 至少一个可移动构件被布置成可滑动地设置在第一和第二止动件之间，以在它们彼此撞击止动件时产生信号，以便在其播放期间指示轴或手柄的某些优选的弧形摆动位置，或指示为 当使用者在俱乐部摆动通过用于击球，定位等的最佳位置之前或之后产生声音时，该摆动的不准确性。

公开(公告)号：US06447800B2

公开(公告)日：2002-09-10

申请号：US08588542

申请日：1996-01-18

申请人： Michael J. Hope

发明人： Michael J. Hope

IPC分类号： A61K9127

CPC分类号： A61K9/1278

摘要： This invention provides methods of loading preformed liposomes by transmembrane permeation induced by alcohols. Solutes loaded into liposomes by this ethanol mediated process include both small nonpolar molecules and larger species, such as proteins and carbohydrates.

摘要翻译： 本发明提供了通过由醇诱导的跨膜渗透来加载预制的脂质体的方法。 通过乙醇介导的方法将负载在脂质体中的溶质包括小的非极性分子和较大的物质，如蛋白质和碳水化合物。