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21. 发明授权

US5478860A Stable microemulsions for hydrophobic compound delivery 失效
标题翻译：用于疏水化合物递送的稳定的微乳液
公开(公告)号：US5478860A
公开(公告)日：1995-12-26
申请号：US071724
申请日：1993-06-04
申请人： Jeffery J. Wheeler , Marcel B. Bally
发明人： Jeffery J. Wheeler , Marcel B. Bally
IPC分类号： A61K9/107 , A61K31/337 , A61K31/335
CPC分类号： A61K31/337 , A61K9/1075
摘要： Microemulsion compositions for the delivery of hydrophobic compounds are provided. Such compositions have a variety of uses. In one embodiment, the hydrophobic compounds are therapeutic agents including drugs. The present invention also discloses methods for in vitro and in vivo delivery of hydrophobic compounds to cells. Uses of the methods in vitro include the testing of hydrophobic compounds for cytotoxicity. Uses of the methods in vivo include diagnostic and therapeutic purposes.
摘要翻译：提供用于递送疏水性化合物的微乳液组合物。这样的组合物具有多种用途。在一个实施方案中，疏水化合物是包括药物在内的治疗剂。本发明还公开了将疏水化合物体外和体内递送至细胞的方法。体外方法的应用包括疏水化合物的细胞毒性测试。体内方法的使用包括诊断和治疗目的。

22. 发明授权

US4885172A Composition for targeting, storing and loading of liposomes 失效
标题翻译：用于靶向，储存和加载脂质体的组合物
公开(公告)号：US4885172A
公开(公告)日：1989-12-05
申请号：US941913
申请日：1986-12-15
申请人： Marcel B. Bally , Helen Loughrey , Pieter R. Cullis
发明人： Marcel B. Bally , Helen Loughrey , Pieter R. Cullis
IPC分类号： A61K9/127 , A61K47/48
CPC分类号： A61K9/1271 , A61K47/48238 , A61K47/48815 , A61K47/48823
摘要： The present invention describes a composition consisting of liposomes covalently or non-covalently coupled to the glycoprotein streptavidin. The streptavidin may additionally be coupled to biotinated proteins such as Immunoglobulin G or monoclonal antibodies.The liposomes of the invention may have a transmembrane potential across their membranes, and may be dehydrated. In addition, the composition may contain ionizable bioactive agents such as antineoplastic agents, and may be used in diagnostic assays.
摘要翻译：本发明描述由与糖蛋白链霉抗生物素蛋白共价或非共价偶联的脂质体组成的组合物。链霉亲和素可以另外与生物素化蛋白例如免疫球蛋白G或单克隆抗体偶联。本发明的脂质体可跨过其膜具有跨膜电位，并且可以脱水。此外，组合物可以含有可离子化的生物活性剂，例如抗肿瘤剂，并且可以用于诊断测定。

23. 发明授权

US5981501A Methods for encapsulating plasmids in lipid bilayers 失效
公开(公告)号：US5981501A
公开(公告)日：1999-11-09
申请号：US484282
申请日：1995-06-07
申请人： Jeffery J. Wheeler , Michael Hope , Pieter R. Cullis , Marcel B. Bally
发明人： Jeffery J. Wheeler , Michael Hope , Pieter R. Cullis , Marcel B. Bally
IPC分类号： A61K9/127 , C12N15/88 , A61K48/00
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.

24. 发明授权

US5399331A Method for protein-liposome coupling 失效
标题翻译：蛋白质 - 脂质体偶联方法
公开(公告)号：US5399331A
公开(公告)日：1995-03-21
申请号：US946806
申请日：1992-09-17
申请人： Helen C. Loughrey , Pieter R. Cullis , Marcel B. Bally , Lewis S. Choi
发明人： Helen C. Loughrey , Pieter R. Cullis , Marcel B. Bally , Lewis S. Choi
IPC分类号： A61K9/127 , A61K38/00 , A61K47/48 , C07D207/40 , C07D207/404 , C07D207/46 , A61K37/22
CPC分类号： C07D207/404 , A61K47/48238 , A61K47/48815 , A61K47/48823 , A61K9/1271 , A61K9/1277 , A61K9/1278 , C07D207/46 , A61K38/00
摘要： This invention relates to a method for synthesizing a substantially pure reactive lipid including, for example, N-[4-(p-maleimidophenyl)-butyryl]phosphatidylethanolamine (MPB-PE) and related compositions. The compositions of the present invention are useful as coupling agents and may be incorporated into liposomes and subsequently coupled to proteins, cofactors and a number of other molecules. A preferred coupling method is also disclosed as are protein conjugates.
摘要翻译：本发明涉及一种合成基本上纯的反应性脂质的方法，包括例如N- [4-（对马来酰亚胺基苯基） - 丁酰基]磷脂酰乙醇胺（MPB-PE）和相关组合物。本发明的组合物可用作偶联剂并且可以掺入脂质体中，随后与蛋白质，辅因子和许多其它分子偶联。还公开了优选的偶联方法，蛋白质共轭物也是如此。

25. 发明授权

US5047245A Novel composition for targeting, storing and loading of liposomes 失效
标题翻译：用于靶向，储存和加载脂质体的新型组合物
公开(公告)号：US5047245A
公开(公告)日：1991-09-10
申请号：US399642
申请日：1989-08-28
申请人： Marcel B. Bally , Helen Loughrey , Pieter R. Gullis
发明人： Marcel B. Bally , Helen Loughrey , Pieter R. Gullis
IPC分类号： A61K9/127 , A61K47/48
CPC分类号： A61K9/1271 , A61K47/48238 , A61K47/48815 , A61K47/48823 , A61K9/1277 , A61K9/1278 , Y10S436/829
摘要： The present invention describes a composition consisting of liposomes covalently or non-covalently coupled to the glycoprotein streptavidin. The streptavidin may additionally be coupled to biotinated proteins such as Immunoglobulin G or monoclonal antibodies. The liposomes of the invention may have a transmembrane potential across their membranes, and may be dehydrated. In addition, the composition may contain ionizable bioactive agents such as antineoplastic agents, and may be used in diagnostic assays.This is a divisional application of copending application Ser. No. 941,913, filed Dec. 15, 1986, which is now U.S. Pat. No. 4,885,172, which is a continuation-in-part of copending application Ser. No. 811,037, which in turn is a continuation-in-part of copending application Ser. No. 749,161, filed June 26, 1985, both now abandoned and copending application Ser. No. 759,419, filed July 26, 1985 now U.S. Pat. No. 4,870,635.
摘要翻译：本发明描述由与糖蛋白链霉抗生物素蛋白共价或非共价偶联的脂质体组成的组合物。链霉亲和素可以另外与生物素化蛋白例如免疫球蛋白G或单克隆抗体偶联。本发明的脂质体可跨过其膜具有跨膜电位，并且可以脱水。此外，组合物可以含有可离子化的生物活性剂，例如抗肿瘤剂，并且可以用于诊断测定。这是共同未决申请书的分案申请。 1986年12月15日提交的美国专利第941,913号。第4,885,172号，这是共同未决申请的部分继续。第811,037号，这又是共同未决申请的部分继续。 1985年6月26日提交的第749,161号现在已经被遗弃和共同未决的申请。 1985年7月26日提交的美国专利第759,419号。第4,870,635号。

26. 发明授权

US5858397A Liposomal formulations of mitoxantrone 失效
标题翻译：米托蒽醌的脂质体制剂
公开(公告)号：US5858397A
公开(公告)日：1999-01-12
申请号：US542341
申请日：1995-10-11
申请人： Howard J. Lim , Thomas D. Madden , Marcel B. Bally , Lana W. Barber , Charmaine W. Chang
发明人： Howard J. Lim , Thomas D. Madden , Marcel B. Bally , Lana W. Barber , Charmaine W. Chang
IPC分类号： A61K9/127 , A61K31/135 , A61K31/136 , A61K31/137 , A61K47/10 , A61K47/24
CPC分类号： A61K31/137 , A61K9/127 , A61K9/1271
摘要： Compositions and methods which are useful for the treatment of solid tumors in a host and which are also useful for increasing the therapeutic index of mitoxantrone in a host. The pharmaceutical compositions are liposomal formulations of mitoxantrone in which the liposomes comprise a mixture of cholesterol and a diacylphosphatidylcholine, preferably 1,2-sn-dimyristoyl-phosphatidylcholine.
摘要翻译：可用于治疗宿主中实体瘤的组合物和方法，其也可用于增加宿主中米托蒽醌的治疗指数。药物组合物是米托蒽醌的脂质体制剂，其中脂质体包含胆固醇和二酰基磷脂酰胆碱的混合物，优选1,2-二 - 二肉豆蔻酰磷脂酰胆碱。

27. 发明授权

US5578320A Method of dehydrating liposomes using protective sugars 失效
标题翻译：使用保护性糖脱水脂质体的方法
公开(公告)号：US5578320A
公开(公告)日：1996-11-26
申请号：US22819
申请日：1993-02-24
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。

28. 发明授权

US5171578A Composition for targeting, storing and loading of liposomes 失效
标题翻译：用于靶向，储存和加载脂质体的组合物
公开(公告)号：US5171578A
公开(公告)日：1992-12-15
申请号：US711294
申请日：1991-06-06
申请人： Marcel B. Bally , Helen Loughrey , Pieter R. Cullis
发明人： Marcel B. Bally , Helen Loughrey , Pieter R. Cullis
IPC分类号： A61K9/127 , A61K47/48
CPC分类号： A61K9/1277 , A61K47/48823 , A61K9/1271 , A61K9/1278 , Y10S436/829 , Y10S530/812
摘要： The present invention describes a composition consisting of liposomes covalently or non-covalently coupled to the glycoprotein streptavidin. The streptavidin may additionally be coupled to biotinated proteins such as Immunoglobulin G or monoclonal antibodies.The liposomes of the invention may have a transmembrane potential across their membranes, and may be dehydrated. In addition, the composition may contain ionizable bioactive agents such as antineoplastic agents, and may be used in diagnostic assays.
摘要翻译：本发明描述由与糖蛋白链霉抗生物素蛋白共价或非共价偶联的脂质体组成的组合物。链霉亲和素可以另外与生物素化蛋白例如免疫球蛋白G或单克隆抗体偶联。本发明的脂质体可跨过其膜具有跨膜电位，并且可以脱水。此外，组合物可以含有可离子化的生物活性剂，例如抗肿瘤剂，并且可以用于诊断测定。

29. 发明授权

US5059421A Preparation of targeted liposome systems of a defined size distribution 失效
标题翻译：制备具有规定尺寸分布的靶向脂质体系统
公开(公告)号：US5059421A
公开(公告)日：1991-10-22
申请号：US370650
申请日：1989-06-23
申请人： Helen C. Loughrey , Pieter R. Cullis , Marcel B. Bally , Lewis S. L. Choi , Kim F. Wong
发明人： Helen C. Loughrey , Pieter R. Cullis , Marcel B. Bally , Lewis S. L. Choi , Kim F. Wong
IPC分类号： A61K9/127 , A61K47/48
CPC分类号： A61K9/1271 , A61K47/48238 , A61K47/48815 , A61K9/1277 , A61K9/1278
摘要： The present invention relates to a general method for producing sized protein-liposome conjugates exhibiting enhanced blood circulation times. The present invention also relates to the sized protein-liposome conjugate compositions produced by the method of the present invention. The protein-liposome conjugates of the present invention preferably range in size from about 75 nm to about 200 nm.The liposomes of the invention may have a transmembrane potential across their membranes, and may be dehydrated. In addition, the composition may contain ionizable bioactive agents such as antineplastic agents, and may be used in diagnostic assays.
摘要翻译：本发明涉及一种生产显示出增强的血液循环时间的大小的蛋白质 - 脂质体缀合物的一般方法。本发明还涉及通过本发明的方法制备的大小的蛋白质 - 脂质体缀合物组合物。本发明的蛋白质 - 脂质体缀合物的大小范围优选为约75nm至约200nm。本发明的脂质体可跨过其膜具有跨膜电位，并且可以脱水。此外，组合物可以含有可离子化的生物活性剂，例如抗变性剂，并且可以用于诊断测定。

30. 发明授权

US5008050A Extrusion technique for producing unilamellar vesicles 失效
标题翻译：用于生产单层囊泡的挤出技术
公开(公告)号：US5008050A
公开(公告)日：1991-04-16
申请号：US310495
申请日：1989-02-13
申请人： Pieter R. Cullis , Michael J. Hope , Marcel B. Bally
发明人： Pieter R. Cullis , Michael J. Hope , Marcel B. Bally
IPC分类号： A61K9/127 , A61K9/133
CPC分类号： A61K9/1277 , B01D61/147 , B01D61/18 , B01D2317/02 , Y10S436/829 , Y10T428/2984
摘要： A method for reducing the lamellarity of a population of liposomes is provided which comprises repeatedly passing the liposomes under pressure through a filter which has a pore size equal to or less than about 100 nm. In certain embodiments, the method is used to convert a population of previously formed multilamellar liposomes into a population of substantially unilamellar liposomes. In accordance with other aspects of the disclosure, liposomes are prepared directly from a lipid powder or pellet and buffer without the use of any solvents, detergents or other extraneous materials.
摘要翻译：提供了一种降低脂质体群体的层状化的方法，其包括在压力下将脂质体重复通过具有等于或小于约100nm的孔径的过滤器。在某些实施方案中，该方法用于将先前形成的多层脂质体的群体转化为基本上单层脂质体的群体。根据本公开的其他方面，脂质体直接由脂质粉末或颗粒和缓冲液制备，而不使用任何溶剂，洗涤剂或其它外来材料。

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