公开(公告)号：WO1995012388A1

公开(公告)日：1995-05-11

申请号：PCT/US1994012579

申请日：1994-11-03

Applicant: THE LIPOSOME COMPANY, INC.

Inventor： THE LIPOSOME COMPANY, INC. ,  OSTRO, Marc, J. ,  JANOFF, Andrew, S. ,  MINCHEY, Sharma, R.

IPC: A61K09/127

CPC classification number: A61K9/1278 ,  A61K9/127 ,  A61K31/557 ,  A61K31/5575

Abstract: This invention provides a method of administering an arachidonic acid metabolite, such as prostaglandin E1, to an animal. The metabolite is given to the animal, typically a human, in association with a unilamellar liposome comprising a lipid and a release-inhibiting aqueous buffer. This method can be used to treat animals afflicted with disorders characterized by cell activation and adhesion, inflammation or toxemia.

Abstract translation: 本发明提供了向动物施用花生四烯酸代谢物如前列腺素E1的方法。 将代谢物与包含脂质和释放抑制性水性缓冲液的单层脂质体相关联地给予动物，通常为人。 该方法可用于治疗以细胞活化和粘附，炎症或毒血症为特征的疾病。

公开(公告)号：WO1994008565A1

公开(公告)日：1994-04-28

申请号：PCT/US1993009878

申请日：1993-10-13

Applicant: THE LIPOSOME COMPANY, INC.

Inventor： THE LIPOSOME COMPANY, INC. ,  BONI, Lawrence, T. ,  JANOFF, Andrew, S. ,  MINCHEY, Sharma, R. ,  PERKINS, Walter, R. ,  SWENSON, Christine, E. ,  AHL, Patrick, L. ,  DAVIS, Thomas, S.

IPC: A61K09/127

CPC classification number: A61K9/1277 ,  A61L2/0011

Abstract: This invention relates to interdigitation-fusion (IF) liposomes and gels. These liposomes and gels capture high solute to lipid ratios, including bioactive agent. This invention also relates to the discovery that the fusion of liposomes to produce IF gel and liposomes according to the present invention is size dependent. The present invention also relates to a method for producing IF liposomes and gels. In the method of the present invention, sized liposomes formed by sonication, extrusion or alternative processes are fused in the presence of ethanol or other suitable inducer. This process results in a composition of the present invention in gel form. To produce liposomes, the gels are exposed to a temperature usually but not necessarily above the transition temperature (Tm) of the lipid used. The temperature required by the methods of the invention is that temperature which induces a change in the material properties of the mixture. The inducer may also be removed. The result is a composition comprising liposomes containing high solute to lipid ratios. The IF liposomes and gels of the present invention may be used in combination with numerous solutes, especially including bioactive agents.

Abstract translation: 本发明涉及分叉融合（IF）脂质体和凝胶。 这些脂质体和凝胶捕获高溶质与脂质比，包括生物活性剂。 本发明还涉及根据本发明的脂质体融合以产生IF凝胶和脂质体的发现，其尺寸依赖性。 本发明还涉及制备IF脂质体和凝胶的方法。 在本发明的方法中，通过超声处理，挤出或替代方法形成的尺寸脂质体在乙醇或其它合适的诱导剂存在下融合。 该方法产生凝胶形式的本发明组合物。 为了生产脂质体，将凝胶暴露于通常但不一定高于所用脂质的转变温度（Tm）的温度。 本发明方法所需的温度是引起混合物的材料性质变化的温度。 诱导剂也可以被去除。 其结果是包含含有高溶质与脂质比的脂质体的组合物。 本发明的IF脂质体和凝胶可以与许多溶质组合使用，特别是包括生物活性剂。

公开(公告)号：WO1992019243A1

公开(公告)日：1992-11-12

申请号：PCT/US1992003895

申请日：1992-05-07

Applicant: THE LIPOSOME COMPANY, INC.

Inventor： THE LIPOSOME COMPANY, INC. ,  OSTRO, Marc, J.

IPC: A61K31/47

CPC classification number: A61K31/5575 ,  A61K9/127 ,  A61K9/1278 ,  A61K31/557

Abstract: A method of treating a cell activation/adhesion syndrome in mammals, including humans, by the administration of a prostaglandin associated with a liposome is disclosed. Such cell activation/adhesion syndromes may include reperfusion injury, septic shock, myocardial infarction, adult respiratory distress syndrome, rheumatoid vasculitis, systemic vasculitis, lupus, post traumatic shock, burn injury or restenosis after angioplasty. In a preferred embodiment, the prostaglandin is encapsulated in the liposomes.

公开(公告)号：WO1991010422A1

公开(公告)日：1991-07-25

申请号：PCT/US1991000259

申请日：1991-01-11

Applicant: THE LIPOSOME COMPANY, INC.

Inventor： THE LIPOSOME COMPANY, INC. ,  BONI, Lawrence, T. ,  JANOFF, Andrew, S. ,  MINCHEY, Sharma, R. ,  PERKINS, Walter, R. ,  SWENSON, Christine, E. ,  AHL, Patrick, L.

IPC: A61K09/133

CPC classification number: A61K9/1277

Abstract: This invention relates to interdigitation-fusion (IF) liposomes and gels. These liposomes and gels capture high solute to lipid ratios, including bioactive agent. This invention also relates to the discovery that the fusion of liposomes to produce IF gel and liposomes according to the present invention is size dependent. The present invention also relates to a method for producing IF liposomes and gels. In the method of the present invention, sized liposomes formed by sonication, extrusion or alternative processes are fused in the presence of ethanol or other suitable inducer. This process results in a composition of the present invention in gel form. To produce liposomes, the gels are exposed to a temperature usually but not necessarily above the transition temperature (Tm) of the lipid used. The temperature required by the methods of the invention is that temperature which induces a change in the material properties of the mixture. The inducer may also be removed. The result is a composition comprising liposomes containing high solute to lipid ratios. The IF liposomes and gels of the present invention may be used in combination with numerous solutes, especially including bioactive agents.

Abstract translation: 本发明涉及分叉融合（IF）脂质体和凝胶。 这些脂质体和凝胶捕获高溶质与脂质比，包括生物活性剂。 本发明还涉及根据本发明的脂质体融合以产生IF凝胶和脂质体的发现，其尺寸依赖性。 本发明还涉及制备IF脂质体和凝胶的方法。 在本发明的方法中，通过超声处理，挤出或替代方法形成的尺寸脂质体在乙醇或其它合适的诱导剂存在下融合。 该方法产生凝胶形式的本发明组合物。 为了生产脂质体，将凝胶暴露于通常但不一定高于所用脂质的转变温度（Tm）的温度。 本发明方法所需的温度是引起混合物的材料性质变化的温度。 诱导剂也可以被去除。 其结果是包含含有高溶质与脂质比的脂质体的组合物。 本发明的IF脂质体和凝胶可以与许多溶质组合使用，特别是包括生物活性剂。

公开(公告)号：WO1991006310A1

公开(公告)日：1991-05-16

申请号：PCT/US1990006291

申请日：1990-10-30

Applicant: THE LIPOSOME COMPANY, INC.

Inventor： THE LIPOSOME COMPANY, INC. ,  BOLCSAK, Lois, E.

IPC: A61K37/22

CPC classification number: A61K9/1272 ,  A61K9/127 ,  A61K31/35

Abstract: Liposomal Cromolyn formulations comprising sodium cromoglycate and a lipid or lipid mixture are disclosed. The lipids employed in the cromolyn liposomal formulations of this invention include cholesterol neutralized cholesterol hydrogen succinate (cholesterol hemisuccinate or ''CHS''); saturated phospholipids such as dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), hydrogenated soy phosphatidylcholine (HSPC); and cholesterol (Chol), or mixtures of same.

Abstract translation: 公开了包含色甘酸钠和脂质或脂质混合物的脂质体克罗莫仑制剂。 在本发明的色甘酸脂质体制剂中使用的脂质包括胆固醇中和的胆固醇琥珀酸氢钙（胆固醇半琥珀酸酯或“CHS”）; 饱和磷脂如二肉豆蔻酰磷脂酰胆碱（DMPC），二棕榈酰磷脂酰胆碱（DPPC），氢化大豆磷脂酰胆碱（HSPC）; 和胆固醇（Chol）或其混合物。

公开(公告)号：WO1989005636A1

公开(公告)日：1989-06-29

申请号：PCT/US1988004632

申请日：1988-12-22

Applicant: THE LIPOSOME COMPANY, INC.

Inventor： THE LIPOSOME COMPANY, INC. ,  MADDEN, Thomas, D.

IPC: A61K09/66

CPC classification number: A61K9/1277

Abstract: A new method is disclosed for making unilamellar vesicles from multilamellar vesicles. Such vesicles are formed without the use of physical or chemical disruption processes known in the art for forming unilamellar vesicles. The liposomes are incubated at neutral pH at or near the transition temperature of the lipids used, in low ionic strength media such as distilled water. The liposomes may comprise bioactive agents, such as the toxic hydrophobic drugs such as the polyene antibiotic amphotericin B, and may be used in vivo or in vitro. Lipid compositions are preferably a combination of the phospholipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) in about a 7:3 mole ratio.

Abstract translation: 公开了一种从多层囊泡制造单层囊泡的新方法。 在不使用本领域已知的用于形成单层囊泡的物理或化学破坏方法的情况下形成这样的囊泡。 将脂质体在等离子体强度介质如蒸馏水中，在所用脂质的转变温度或接近温度的中性pH下孵育。 脂质体可以包含生物活性剂，例如毒性疏水性药物如多烯抗生素两性霉素B，并且可以在体内或体外使用。 脂质组合物优选为约7:3摩尔比的磷脂二肉豆蔻酰磷脂酰胆碱（DMPC）和二肉豆蔻酰磷脂酰甘油（DMPG）的组合。

公开(公告)号：WO1987004347A1

公开(公告)日：1987-07-30

申请号：PCT/US1987000143

申请日：1987-01-22

Applicant: THE LIPOSOME COMPANY, INC.

Inventor： THE LIPOSOME COMPANY, INC. ,  TILCOCK, Colin, P., S. ,  CULLIS, Pieter, R. ,  HOPE, Michael, J. ,  JANOFF, Andrew, S.

IPC: A61K31/685

CPC classification number: A61K9/1277 ,  A61K9/0019 ,  A61K47/24

Abstract: A method and composition for the solubilization of hydrophobic materials using a lysophospholipid. The method includes drying a composition comprising a hydrophobic material-solubilizing effective amount of phospholipid from organic solvent and hydrating the resulting film with an aqueous medium at either a pH of between about 8.5 and about 14.0, or at pH 7.0 followed by reduction of the temperature to less than 0oC.

公开(公告)号：WO1987000043A1

公开(公告)日：1987-01-15

申请号：PCT/US1986001371

申请日：1986-06-24

Applicant: THE LIPOSOME COMPANY, INC.

Inventor： THE LIPOSOME COMPANY, INC. ,  BALLY, Marcel, B. ,  CULLIS, Pieter, R. ,  HOPE, Michael, J. ,  JANOFF, Andrew, S. ,  MAYER, Lawrence, D.

IPC: A61K09/00

CPC classification number: A61K9/1277

Abstract: A multilamellar vesicle dispersed in an aqueous phase comprising an aqueous medium, a lipid concentration of at least about 50 mg/ml and a trapping efficiency of at least about 30 percent. The vesicle can be prepared by dispersing the lipid in an aqueous phase to form a multilamellar vesicle, rapidly freezing the multilamellar vesicle to obtain a frozen lipid-aqueous medium mixture, and warming the mixture to obtain a frozen and thawed multilamellar vesicle dispersed in an aqueous phase.

Abstract translation: 分散在包含水性介质的水相中的多层囊泡，至少约50mg / ml的脂质浓度和至少约30％的捕获效率。 可以通过将脂质分散在水相中以形成多层囊泡，快速冷冻多层囊泡以获得冷冻的脂质 - 水性介质混合物，并加热混合物以获得分散在水溶液中的冷冻和解冻的多层囊泡， 相。

公开(公告)号：WO1995018620A1

公开(公告)日：1995-07-13

申请号：PCT/US1995000370

申请日：1995-01-11

Applicant: THE LIPOSOME COMPANY, INC.

Inventor： THE LIPOSOME COMPANY, INC. ,  JANOFF, Andrew, S. ,  EIERMAN, David, F.

IPC: A61K31/557

CPC classification number: A61K9/127 ,  A61K31/557

Abstract: Provided herein is a method of administering a free arachidonic acid metabolite to an animal, the method involving administration of the free metabolite and an endocytosable particle. This method can be used to treat animals afflicted with disorders characterized by cell activation and adhesion, inflammation or toxemia. Also provided is a method of treating an animal for such disorders by administration to the animals of a composition containing an anti-disorder effective amount of an endocytosable particle.

Abstract translation: 本文提供了向动物施用游离花生四烯酸代谢物的方法，该方法涉及施用游离代谢物和可内吞颗粒。 该方法可用于治疗以细胞活化和粘附，炎症或毒血症为特征的疾病。 还提供了一种通过向动物施用含有抗障碍有效量的可内吞颗粒的组合物来治疗动物这种疾病的方法。

公开(公告)号：WO1995011670A1

公开(公告)日：1995-05-04

申请号：PCT/US1994012167

申请日：1994-10-25

Applicant: THE LIPOSOME COMPANY, INC.

Inventor： THE LIPOSOME COMPANY, INC. ,  JANOFF, Andrew, S. ,  PERKINS, Walter ,  AHMAD, Imran

IPC: A61K09/127

CPC classification number: A61K38/17 ,  A61K9/127

Abstract: Defensis are microbicidal, tumoricidal cytotoxic protein componenents of animal host defense systems. They can be entrapped in liposomes containing release-inhibiting lipid such that the defensins are neutralized, and their release from the liposomes is inhibited; however, the defensins remain effective when exposed to endocytosed material in endocytic vesicles. Liposomal defensin formulations are administered to animals for the treatment or prevention of microbial infections, for the treatment of cancers and for the treatment of disorders characterized by a deficiency of protein-mediated cytotoxic activity in cytoplasmic granules.

Abstract translation: Defensis是动物宿主防御系统的杀菌，杀肿瘤细胞毒性蛋白质成分。 它们可以被包裹在含有释放抑制脂质的脂质体中，使得防御素被中和，并且它们从脂质体的释放被抑制; 然而，防御素在暴露于内吞囊泡中的内吞物质时仍然有效。 向动物施用脂质体防御素制剂用于治疗或预防微生物感染，用于治疗癌症和用于治疗以细胞质颗粒中蛋白质介导的细胞毒活性缺乏为特征的病症。