公开(公告)号：US20060240009A1

公开(公告)日：2006-10-26

申请号：US11472140

申请日：2006-06-20

申请人： Samuel Zalipsky ,  Theresa Allen ,  Shi Huang

发明人： Samuel Zalipsky ,  Theresa Allen ,  Shi Huang

IPC分类号： A61K39/395 ,  A61K9/127

CPC分类号： A61K9/1272 ,  A61K9/1271 ,  A61K47/6913

摘要： A liposomal composition and a method of using the same for achieving intracellular delivery of a liposome-entrapped agent is described. The liposomes are composed of a pH sensitive lipid and include a targeting ligand to direct the liposomes to a target cell. The liposomes also include a stabilizing component, such a polymer-derivatized lipid, where the polymer is attached to the lipid by a releasable linkage. Administration of the liposomes results in cellular internalization and destabilization of the liposome for intracellular delivery of the entrapped agent.

公开(公告)号：US20060246126A1

公开(公告)日：2006-11-02

申请号：US11479437

申请日：2006-06-30

申请人： Theresa Allen ,  Paul Uster ,  Francis Martin ,  Samuel Zalipsky

发明人： Theresa Allen ,  Paul Uster ,  Francis Martin ,  Samuel Zalipsky

IPC分类号： A61K39/395 ,  A61K9/127 ,  C07K16/46

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： Reagents for use in preparing a therapeutic liposome composition sensitized to a target cell are described. The reagents include a liposomal composition composed of pre-formed liposomes having an entrapped therapeutic agent and a plurality of targeting conjugates composed of a lipid, a hydrophilic polymer and a targeting ligand. The therapeutic, target-cell sensitized liposome composition is formed by incubating the liposomal composition with a selected conjugate.

公开(公告)号：US20050169980A1

公开(公告)日：2005-08-04

申请号：US11050012

申请日：2005-02-02

申请人： Theresa Allen ,  Paul Uster ,  Francis Martin ,  Samuel Zalipsky

发明人： Theresa Allen ,  Paul Uster ,  Francis Martin ,  Samuel Zalipsky

IPC分类号： A61K9/127 ,  A61K51/12 ,  A61K39/395

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： Reagents for use in preparing a therapeutic liposome composition sensitized to a target cell are described. The reagents include a liposomal composition composed of pre-formed liposomes having an entrapped therapeutic agent and a plurality of targeting conjugates composed of a lipid, a hydrophilic polymer and a targeting ligand. The therapeutic, target-cell sensitized liposome composition is formed by incubating the liposomal composition with a selected conjugate.

公开(公告)号：US20050136064A1

公开(公告)日：2005-06-23

申请号：US11049848

申请日：2005-02-02

申请人： Theresa Allen ,  Paul Uster ,  Francis Martin ,  Samuel Zalipsky

发明人： Theresa Allen ,  Paul Uster ,  Francis Martin ,  Samuel Zalipsky

IPC分类号： A61K9/127 ,  A61K51/12 ,  A61K39/395 ,  C07K16/46 ,  C12N9/00

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： Reagents for use in preparing a therapeutic liposome composition sensitized to a target cell are described. The reagents include a liposomal composition composed of pre-formed liposomes having an entrapped therapeutic agent and a plurality of targeting conjugates composed of a lipid, a hydrophilic polymer and a targeting ligand. The therapeutic, target-cell sensitized liposome composition is formed by incubating the liposomal composition with a selected conjugate.

摘要翻译： 描述了用于制备对目标细胞敏化的治疗性脂质体组合物的试剂。 试剂包括由预先形成的脂质体组成的脂质体组合物，其具有包埋的治疗剂和由脂质，亲水性聚合物和靶向配体组成的多种靶向缀合物。 通过将脂质体组合物与所选择的缀合物孵育来形成治疗性靶细胞致敏脂质体组合物。

公开(公告)号：US20050260261A1

公开(公告)日：2005-11-24

申请号：US11133879

申请日：2005-05-19

申请人： Shi Huang ,  Samuel Zalipsky ,  Wei-Ming Zhang ,  Bei Jin ,  Yolanda Quinn

发明人： Shi Huang ,  Samuel Zalipsky ,  Wei-Ming Zhang ,  Bei Jin ,  Yolanda Quinn

IPC分类号： C07D233/02 ,  A61K9/127 ,  A61K31/7105 ,  A61K31/711 ,  A61K47/22 ,  A61K47/44 ,  A61K48/00 ,  A61P35/00 ,  A61P43/00 ,  C07D233/54

CPC分类号： A61K9/1271 ,  A61K9/1272 ,  A61K47/542 ,  A61K47/543 ,  A61K48/00 ,  C07D233/54 ,  C07D233/64 ,  Y10T428/2984

摘要： A lipid represented by the formula: wherein each of R1 and R2 is an alkyl or alkenyl chain having between about 8 to about 24 carbon atoms; n=0-20; L is selected from the group consisting of (i) —X—(C═O)—Y—, (ii) —X—(C═O)—, and (iii) —X—CH2—, wherein X and Y are independently selected from oxygen, NH and a direct bond; and Z is a weakly basic moiety that has a pK of less than about 7.4 and greater than about 4.0 is described.

摘要翻译： 由下式表示的脂质：其中R 1和R 2各自为具有约8至约24个碳原子的烷基或链烯基链; n = 0-20; L选自（i）-X-（CO）-Y-，（ii）-X-（CO） - 和（iii）-X-CH 2 - 其中X和Y独立地选自氧，NH和直接键; 并且Z是具有小于约7.4且大于约4.0的pK的弱碱性部分。

公开(公告)号：US20050191344A1

公开(公告)日：2005-09-01

申请号：US11036523

申请日：2005-01-13

申请人： Samuel Zalipsky ,  Weiming Zhang ,  Kew Shi Huang

发明人： Samuel Zalipsky ,  Weiming Zhang ,  Kew Shi Huang

IPC分类号： A61K9/127 ,  A61K47/00 ,  A61K47/48 ,  A61K48/00

CPC分类号： A61K9/1272 ,  A61K9/1273 ,  A61K47/544 ,  A61K47/6911 ,  A61K48/0008 ,  A61K48/0025 ,  A61K48/0041

摘要： A neutral cationic lipid and liposomes prepared from the neutral cationic lipid are described. Liposomes comprised of the lipid are suitable for delivery of a polyanionic compound, such as a nucleic acid. The delivery can be performed in vivo or ex vivo. The neutral cationic lipid, which is neutral in charge at physiologic pH and positively charged at pH values less than physiologic pH, contains a polar head group that imparts solubility of the lipid and permits its packing into a liposomal lipid bilayer.

摘要翻译： 描述了由中性阳离子脂质制备的中性阳离子脂质和脂质体。 由脂质组成的脂质体适合于递送聚阴离子化合物，例如核酸。 递送可以在体内或体外进行。 中性阳离子脂质在生理pH值为中性，pH值小于生理pH值时带正电，含有极性头基团，赋予脂质溶解性并允许其包入脂质体脂质双层。

公开(公告)号：US07592307B2

公开(公告)日：2009-09-22

申请号：US11810931

申请日：2007-06-06

申请人： Samuel Zalipsky ,  Radwan Kiwan

发明人： Samuel Zalipsky ,  Radwan Kiwan

IPC分类号： A01N37/18 ,  A61K38/00 ,  C08B11/00 ,  C25D3/60 ,  A61K9/127

CPC分类号： A61K47/554 ,  A61K47/54 ,  A61K47/542 ,  A61K47/543 ,  A61K47/544 ,  A61K47/60

摘要： A conjugate comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-, hydroxy- or carboxyl-containing ligand is described. The resulting conjugate is capable of releasing the parent amine, hydroxy, or carboxyl-containing compound via thiol-mediated cleavage. The system allows for delivery of various amino-, hydroxy-, or carboxy-containing drugs in the form of their thiolytically cleavable macromolecular conjugates.

摘要翻译： 描述了由共价但可逆地连接到含胺，羟基或羧基的配体的亲水性聚合物组成的缀合物。 所得的缀合物能够通过硫醇介导的切割释放母体胺，羟基或含羧基的化合物。 该系统允许以其可硫裂解的大分子缀合物的形式递送各种氨基，羟基或羧基的药物。

公开(公告)号：US07303760B2

公开(公告)日：2007-12-04

申请号：US10714085

申请日：2003-11-14

申请人： Samuel Zalipsky ,  Alberto Gabizon

发明人： Samuel Zalipsky ,  Alberto Gabizon

IPC分类号： A61K9/127 ,  C07F9/02 ,  C07F53/00 ,  C07F321/00

CPC分类号： A61K31/407 ,  A61K47/543 ,  A61K47/6911

摘要： Methods for administering mitomycin C to a multi-drug resistant cell and for reducing the toxicity of the compound are described. In the methods, mitoymic C is provided in the form of a prodrug conjugate, where the drug is linked to a hydrophobic moiety, such as a lipid, through a cleavable dithiobenzyl linkage. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of mitomycin C in its original form. The linkage is stable under nonreducing conditions. The prodrug conjugate can be incorporated into liposomes for administration in vivo and release of mitomycin C in response to endogenous in vivo reducing conditions or in response to administration of an exogenous reducing agent.

摘要翻译： 描述了向多药耐药细胞施用丝裂霉素C并降低化合物的毒性的方法。 在该方法中，丝裂蛋白C以前体药物缀合物的形式提供，其中药物通过可裂解的二硫代苄基键连接到疏水部分，例如脂质。 二硫代苄基键易受到轻度硫解的裂解，导致丝裂霉素C以其原始形式释放。 在非还原条件下，连接是稳定的。 可以将前体药物缀合物掺入用于体内施用的体内脂质体中，并响应内源性体内还原条件或响应外源性还原剂的施用而释放丝裂霉素C.

公开(公告)号：US07276248B2

公开(公告)日：2007-10-02

申请号：US11202913

申请日：2005-08-12

申请人： Samuel Zalipsky ,  Alberto A. Gabizon

发明人： Samuel Zalipsky ,  Alberto A. Gabizon

IPC分类号： A61K9/127 ,  C07F9/02 ,  C07F53/00 ,  C07C321/00

CPC分类号： A61K9/1271 ,  A61K9/0019 ,  A61K31/196 ,  A61K31/407 ,  A61K31/519 ,  A61K31/56 ,  A61K38/14 ,  A61K47/54 ,  A61K47/542 ,  A61K47/543 ,  A61K47/544 ,  A61K47/554 ,  A61K47/60 ,  A61K47/6911 ,  C07C323/19 ,  C07D239/553 ,  C07D487/14 ,  C07H17/08 ,  C07H19/12 ,  C07H19/16 ,  Y10T428/2984

摘要： Conjugates of a hydrophobic moiety, such as a lipid, linked through a cleavable dithiobenzyl linkage to a therapeutic agent are described. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of the therapeutic agent in its original form. The linkage is stable under nonreducing conditions. The conjugate can be incorporated into liposomes for administration in vivo and release of the therapeutic agent in response to endogeneous in vivo reducing conditions or in response to administration of an exogeneous reducing agent.

摘要翻译： 描述了通过可切割二硫代苄基键连接到治疗剂的疏水部分（例如脂质）的缀合物。 二硫代苄基键易受到轻度硫解的裂解，导致治疗剂以其原始形式释放。 在非还原条件下，连接是稳定的。 缀合物可以并入脂质体中，用于体内施用和响应于体内还原条件或响应于外源性还原剂的施用释放治疗剂。

公开(公告)号：US07160554B2

公开(公告)日：2007-01-09

申请号：US10438502

申请日：2003-05-14

申请人： Samuel Zalipsky ,  Martin C. Woodle ,  Francis J. Martin ,  Yechezkel Barenholz ,  Herve Bercovier

发明人： Samuel Zalipsky ,  Martin C. Woodle ,  Francis J. Martin ,  Yechezkel Barenholz ,  Herve Bercovier

IPC分类号： A61K9/127

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。