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公开(公告)号：US06660525B2
公开(公告)日：2003-12-09
申请号：US09501857
申请日：2000-02-10
IPC分类号： C12N1586
CPC分类号： A61K9/1273 , A61K9/1271
摘要： A method of liposome-based therapy for a mammalian subject is disclosed. The method uses liposomes with outer surfaces that contain an affinity moiety effective to bind specifically to a biological surface at which the therapy is aimed, and a hydrophilic polymer coating effective to shield the affinity moiety from interaction with the target surface. The hydrophilic polymer coating is made up of polymer chains covalently linked to surface lipid components in the liposomes through releasable linkages. After a desired liposome biodistribution is achieved, a releasing agent is administered to cause cleaving of a substantial portion of the releasable linkages in the liposomes, to expose the affinity agent to the target surface.
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公开(公告)号：US06224903B1
公开(公告)日：2001-05-01
申请号：US09208684
申请日：1998-12-10
申请人： Francis J. Martin , Samuel Zalipsky
发明人： Francis J. Martin , Samuel Zalipsky
IPC分类号： A61K9127
CPC分类号： A61K9/1272 , A61K9/1271
摘要： A fusogenic liposome composition for delivering a liposome-entrapped compound into the cytoplasm of a target cell is described. The liposomes have an outer surface coating of chemically releasable hydrophilic polymer chains which shield hydrophobic polymers on the liposome outer surface. Release of the hydrophilic polymer chains exposes the hydrophobic polymers for interaction with outer cell membranes of the target cells to promote fusion of the liposome with the target cells. Also disclosed is a polymer-lipid conjugate for use in promoting fusion between target membranes. The conjugate is composed of a first segment composed of a hydrophilic polymer and a second hydrophobic polymer segment. The second segment is joined to the first segment by a bond effective to release the first segment in response to an existing or an induced physiologic condition. Attached to the second segment is a vesicle-forming lipid member.
摘要翻译： 描述了用于将脂质体包埋的化合物递送到靶细胞的细胞质中的融合脂质体组合物。 脂质体具有化学上可释放的亲水性聚合物链的外表面涂层，其在脂质体外表面上屏蔽疏水性聚合物。 亲水性聚合物链的释放使疏水性聚合物暴露于与靶细胞的外细胞膜相互作用，以促进脂质体与靶细胞的融合。 还公开了用于促进靶膜之间的融合的聚合物 - 脂质缀合物。 缀合物由由亲水性聚合物和第二疏水性聚合物链段构成的第一链段组成。 第二段通过有效释放第一段的键与第一段连接，以响应于现有或诱导的生理状况。 附着于第二段是形成囊泡的脂质成分。
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公开(公告)号：US06180134B2
公开(公告)日：2001-01-30
申请号：US08480332
申请日：1995-06-07
IPC分类号： A61K9127
CPC分类号： A61K9/0019 , A61K9/1271 , A61K31/00 , A61K38/12 , A61K38/1774 , A61K47/61 , A61K47/62 , A61K47/6911 , Y10S424/812 , A61K2300/00
摘要： A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.
摘要翻译： 公开了包含小的表面结合效应分子的脂质体组合物。 脂质体具有亲水性聚合物链的表面层，用于增强血流中的循环时间。 效应分子连接到聚合物链的末端。 在一个实施方案中，效应物是多粘菌素B，用于治疗败血性休克。
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公开(公告)号：US5891468A
公开(公告)日：1999-04-06
申请号：US949046
申请日：1997-10-10
申请人： Francis J. Martin , Samuel Zalipsky
发明人： Francis J. Martin , Samuel Zalipsky
CPC分类号： A61K9/1272 , A61K9/1271 , Y10S436/829
摘要： A fusogenic liposome composition for delivering a liposome-entrapped compound into the cytoplasm of a target cell is described. The liposomes have an outer surface coating of chemically releasable hydrophilic polymer chains which shield hydrophobic polymers on the liposome outer surface. Release of the hydrophilic polymer chains exposes the hydrophobic polymers for interaction with outer cell membranes of the target cells to promote fusion of the liposome with the target cells. Also disclosed is a method for using the composition to deliver a compound to target cells, and a method for selecting suitable hydrophobic polymers for use in the composition.
摘要翻译： 描述了用于将脂质体包埋的化合物递送到靶细胞的细胞质中的融合脂质体组合物。 脂质体具有化学上可释放的亲水性聚合物链的外表面涂层，其在脂质体外表面上屏蔽疏水性聚合物。 亲水性聚合物链的释放使疏水性聚合物暴露于与靶细胞的外细胞膜相互作用，以促进脂质体与靶细胞的融合。 还公开了使用该组合物将化合物递送至靶细胞的方法，以及选择用于组合物中的合适的疏水性聚合物的方法。
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公开(公告)号：US5620689A
公开(公告)日：1997-04-15
申请号：US475050
申请日：1995-06-07
CPC分类号： A61K47/48369 , A61K47/48561 , A61K47/48823 , A61K9/1271 , Y10S424/812
摘要： A method of treating a subject having a disorder characterized by a neoplasm of B-lymphocyte or T-lymphocyte lineage cells is described. The method includes administering a suspension of liposomes having a surface coating of polyethylene glycol chains. Attached to the distal ends of the chains are antibodies or antibody fragments effective to bind to an antigen specific to the affected cells. In one embodiment, anti-CD19 antibodies are attached to the liposome-bound chains, for treatment of multiple myeloma.
摘要翻译： 描述了治疗以B淋巴细胞或T淋巴细胞谱系细胞的肿瘤为特征的疾病的受试者的方法。 该方法包括给予具有聚乙二醇链表面包被的脂质体的悬浮液。 连接到链的末端是有效结合受影响细胞特异性抗原的抗体或抗体片段。 在一个实施方案中，抗CD19抗体连接到脂质体结合链上，用于治疗多发性骨髓瘤。
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公开(公告)号：US5527528A
公开(公告)日：1996-06-18
申请号：US40544
申请日：1993-03-31
CPC分类号： C07F9/5537 , A61K47/48815 , A61K47/48823 , A61K9/1271 , Y10S424/812
摘要： A method of administering an anti-tumor compound to a subject is disclosed. The method includes administering to a subject liposomes having sizes predominantly in the range 0.05 to 0.12 microns, and containing an anti-tumor compound in liposome-entrapped form, a surface coating of polyethylene glycol chains, at a surface concentration thereof sufficient to extend the blood circulation time of the liposomes severalfold over that of liposomes in the absence of such coating, and surface-attached antibody molecules effective to bind specifically to tumor-associated antigens present at the tumor site. One liposome composition includes doxorubicin in entrapped form, and, on the liposome surface, a monoclonal antibody against highly proliferating cells in a lung squamous cell carcinoma.
摘要翻译： 公开了向受试者施用抗肿瘤化合物的方法。 该方法包括向主体脂质体施用主要在0.05至0.12微米范围内的脂质体，并且含有脂质体包埋形式的抗肿瘤化合物，其表面浓度足以延长血液的聚乙二醇链的表面包衣 在不存在这种涂层的情况下脂质体的循环时间比脂质体的循环时间多几倍，以及有效结合肿瘤位点处的肿瘤相关抗原的表面附着的抗体分子。 一种脂质体组合物包括夹心形式的多柔比星，和在脂质体表面上的抗肺鳞状细胞癌中高增殖细胞的单克隆抗体。
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公开(公告)号：US06958241B2
公开(公告)日：2005-10-25
申请号：US10616094
申请日：2003-07-08
IPC分类号： A61K9/127 , A61K31/715 , A61K38/00 , A61K47/30 , A61P29/00 , A61P35/00 , C12N5/02 , C12N15/88 , C12N5/06 , C12N5/12
CPC分类号： A61K9/1273 , A61K9/1271
摘要： A method of liposome-based therapy for a mammalian subject is disclosed. The method uses liposomes with outer surfaces that contain an affinity moiety effective to bind specifically to a biological surface at which the therapy is aimed, and a hydrophilic polymer coating effective to shield the affinity moiety from interaction with the target surface. The hydrophilic polymer coating is made up of polymer chains covalently linked to surface lipid components in the liposomes through releasable linkages. After a desired liposome biodistribution is achieved, a releasing agent is administered to cause cleaving of a substantial portion of the releasable linkages in the liposomes, to expose the affinity agent to the target surface.
摘要翻译： 公开了一种哺乳动物受试者基于脂质体的治疗方法。 该方法使用具有外表面的脂质体，其具有有效结合治疗目的的生物表面的亲和部分，以及有效屏蔽亲和部分与靶表面相互作用的亲水性聚合物涂层。 亲水性聚合物涂层由通过可释放键连接到脂质体中的表面脂质组分的聚合物链组成。 在实现期望的脂质体生物分布之后，施用释放剂以引起脂质体中大部分可释放连接的切割，以将亲和剂暴露于靶表面。
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公开(公告)号：US06936272B2
公开(公告)日：2005-08-30
申请号：US10016324
申请日：2001-12-10
申请人： Francis J. Martin , Samuel Zalipsky
发明人： Francis J. Martin , Samuel Zalipsky
CPC分类号： A61K9/1271 , A61K9/127 , A61K9/1272 , A61K47/544 , A61K47/61 , A61K47/62 , A61K47/6849 , A61K47/6911 , A61K47/6913 , A61K51/1234 , C07K16/2854 , C07K2317/55 , Y10S424/812 , Y10S436/829
摘要： A fusogenic liposome composition for delivering a liposome-entrapped compound into the cytoplasm of a target cell is described. The liposomes have an outer surface coating of chemically releasable hydrophilic polymer chains which shield hydrophobic polymers on the liposome outer surface. Release of the hydrophilic polymer chains exposes the hydrophobic polymers for interaction with outer cell membranes of the target cells to promote fusion of the liposome with the target cells. Also disclosed is a method for using the composition to deliver a compound to target cells, and a method for selecting suitable hydrophobic polymers for use in the composition.
摘要翻译： 描述了用于将脂质体包埋的化合物递送到靶细胞的细胞质中的融合脂质体组合物。 脂质体具有化学上可释放的亲水性聚合物链的外表面涂层，其在脂质体外表面上屏蔽疏水性聚合物。 亲水性聚合物链的释放使疏水性聚合物暴露于与靶细胞的外细胞膜相互作用，以促进脂质体与靶细胞的融合。 还公开了使用该组合物将化合物递送至靶细胞的方法，以及选择用于组合物中的合适的疏水性聚合物的方法。
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公开(公告)号：US06326353B1
公开(公告)日：2001-12-04
申请号：US08035443
申请日：1993-03-23
IPC分类号： A61K3812
CPC分类号： A61K9/1271 , A61K47/62 , A61K47/6911 , Y10S530/812
摘要： A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.
摘要翻译： 公开了包含小的表面结合效应分子的脂质体组合物。 脂质体具有亲水性聚合物链的表面层，用于增强血流中的循环时间。 效应分子连接到聚合物链的末端。 在一个实施方案中，效应物是多粘菌素B，用于治疗败血性休克。
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公开(公告)号：US5631018A
公开(公告)日：1997-05-20
申请号：US317723
申请日：1994-10-04
IPC分类号： A61K9/127 , A61K47/32 , A61K47/34 , A61K47/48 , C08F289/00 , C08G69/10 , C08G69/48 , C08G73/02 , C08G73/10 , C08G81/02
CPC分类号： A61K9/1271 , Y10T428/2984
摘要： A lipid-polymer conjugate for use in forming long-circulating liposomes is disclosed. The conjugate includes a vesicle-forming lipid having covalently attached to its polar head group, one of the polymers: polyvinylpyrrolidone, polyvinylmethylether, polyhydroxypropyl methacrylate, polyhydroxypropylmethacrylamide, polyhydroxyethyl acrylate, polymethacrylamide, polydimethylacrylamide, polymethyloxazoline, polyethyloxazoline, polyhydroxyethyloxazoline, polyhydroxypropyloxazoline, or polyaspartamide. A method for preparing liposomes containing the lipid-polymer conjugate is also disclosed.
摘要翻译： 公开了用于形成长循环脂质体的脂质 - 聚合物缀合物。 缀合物包括与其极性头基共价连接的囊泡形成脂质，聚合物之一：聚乙烯吡咯烷酮，聚乙烯基甲基醚，聚羟基丙基甲基丙烯酸酯，聚羟基丙基甲基丙烯酰胺，聚羟基乙基丙烯酸酯，聚甲基丙烯酰胺，聚二甲基丙烯酰胺，聚甲基恶唑啉，聚乙基恶唑啉，聚羟乙基唑啉，聚羟基丙基恶唑啉或聚天冬酰胺。 还公开了一种制备含有脂质 - 聚合物缀合物的脂质体的方法。
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