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公开(公告)号：US20050271715A1
公开(公告)日：2005-12-08
申请号：US11202913
申请日：2005-08-12
申请人： Samuel Zalipsky , Alberto Gabizon
发明人： Samuel Zalipsky , Alberto Gabizon
IPC分类号： A61K9/127 , A61K31/196 , A61K31/407 , A61K31/519 , A61K31/56 , A61K38/00 , A61K47/48 , A61P35/00 , C07C323/12 , C07C323/19 , C07D239/47 , C07D239/54 , C07D239/553 , C07D473/12 , C07D475/02 , C07D487/14 , C07H17/08 , C07H19/12 , C07H19/16 , C07K7/64
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。
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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.
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公开(公告)号：US20060062842A1
公开(公告)日：2006-03-23
申请号：US11220901
申请日：2005-09-06
IPC分类号： A61K9/127 , A61K38/16 , A61K31/704
CPC分类号： A61K31/704 , A61K9/1271
摘要： A composition for administration of a therapeutic compound to a multi-drug resistant cell in a person suffering from a drug-resistant cancer is described. The composition is composed of a carrier molecule and a folate targeting ligand, which is covalently attached to the carrier, and the therapeutic compound. In one preferred embodiment, the carrier is a liposome having a surface coating of hydrophilic polymer chains where a folate ligand is attached to the free distal end of at least a portion of the hydrophilic polymer chains, and the therapeutic agent is entrapped in the liposomes. The composition is effective to achieve accumulation of the therapeutic compound in the cell in an amount sufficient to be cytotoxic. Also described are methods for administering a therapeutic compound to a person suffering from a multi-drug resistant condition.
摘要翻译： 描述了一种用于在耐药性癌症患者中向多药耐药细胞施用治疗化合物的组合物。 组合物由载体分子和共价连接到载体的叶酸靶向配体和治疗化合物组成。 在一个优选的实施方案中，载体是具有亲水性聚合物链的表面涂层的脂质体，其中叶酸配体连接至亲水性聚合物链的至少一部分的游离远端，并且治疗剂被截留在脂质体中。 该组合物有效地实现治疗化合物在细胞中以足以成为细胞毒性的量的积累。 还描述了向患有多重耐药性病症的人施用治疗化合物的方法。
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公开(公告)号：US20050129753A1
公开(公告)日：2005-06-16
申请号：US10988275
申请日：2004-11-12
IPC分类号： A61K9/127 , A61K31/704 , A61K31/404
CPC分类号： A61K9/127 , A61K31/704
摘要： A liposome composition having a protonatable therapeutic agent entrapped in the form of a salt with an glucuronate anion is disclosed. Methods for preparing the composition using an ammonium ion transmembrane gradient having glucuronate as the counterion are also disclsoed. In one embodiment where the protonatable agent is doxorubicin, the method of the invention has comparable loading efficiency, faster release rate, without compromising the therapeutic efficacy compared to loading with an ammonium ion gradient having sulfate as the counterion.
摘要翻译： 公开了一种具有以葡萄糖醛酸盐阴离子盐形式包埋的可质子治疗剂的脂质体组合物。 使用具有葡萄糖醛酸盐作为抗衡离子的铵离子跨膜梯度制备组合物的方法也被揭示。 在可质子化剂是多柔比星的一个实施方案中，与用硫酸盐作为抗衡离子的铵离子梯度负载相比，本发明的方法具有相当的加载效率，更快的释放速率，而不会降低治疗功效。
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公开(公告)号：US20180071253A1
公开(公告)日：2018-03-15
申请号：US15559395
申请日：2016-03-17
发明人： Alberto Gabizon , Patricia Ohana
IPC分类号： A61K31/407 , A61K9/127 , A61K9/00
CPC分类号： A61K31/407 , A61K9/0034 , A61K9/1271
摘要： The present disclosure related to a method of treating bladder cancer in a subject in need of treatment, by administering to the subject an amount of a prodrug of mitomycin C that yields a therapeutically effective amount of mitomycin C. In one embodiment, the prodrug of mitomycin C is a liposomal-prodrug of mitomycin C. In another embodiment, the liposomal-prodrug of mitomycin C is a folate-targeted liposomal-prodrug of mitomycin C.
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公开(公告)号：US5043166A
公开(公告)日：1991-08-27
申请号：US436469
申请日：1989-11-14
IPC分类号： A61K9/127
摘要： A drug/liposome composition comprising an aqueous suspension of liposomes and, entrapped in the lipid bilayer region of the liposomes, an anthraquinone drug containing quinone and hydroquinone functionalities on adjacent anthracene rings. An iron-specific trihydroxamic chelating agent contained in the bulk aqueous phase of the suspension and a lipophilic free-radical scavenger contained in the bilayer region of the liposome cooperate to reduce chemical modification of both drug and lipid components of the composition. A preferred composition containing doxorubicin and alpha-tocopherol entrapped in the liposomes, and ferrioxamine in the aqueous suspension phase is effective in treating human neoplasms, with significantly reduced side effects over those produced by free-drug administration.
摘要翻译： 一种药物/脂质体组合物，其包含脂质体的水性悬浮液，并且包埋在脂质体的脂质双层区域中，在相邻的蒽环上含有醌和氢醌官能团的蒽醌药物。 包含在悬浮液的本体水相中的铁特异性三羟肟酸螯合剂和包含在脂质体的双层区域中的亲脂性自由基清除剂配合以减少组合物的药物和脂质组分的化学修饰。 包含在脂质体中的多柔比星和α-生育酚的优选组合物和含水悬浮相中的铁草胺在治疗人类肿瘤方面是有效的，与通过游离药物给药产生的副作用相比显着降低。
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7.发明申请公开(公告)号：US20080058294A1
公开(公告)日：2008-03-06
申请号：US11662172
申请日：2005-09-11
CPC分类号： A61K9/127 , A61K9/1271 , A61K31/573
摘要： The present invention provides pharmaceutical compositions comprising a glucocorticoid or glucocorticoid derivative stably encapsulated in a liposome. The glucocorticoid or glucocorticoid derivative is selected from an amphipathic weak base glucocorticoid or glucocorticoid derivative having a pKa equal or below 11 and a logD at pH 7 in the range between −2.5 and 1.5; or an amphipathic weak acid GC or GC derivative having a pKa above 3.5 and a logD at pH 7 in the range between −2.5 and 1.5. The therapeutic effect of the pharmaceutical composition of the invention was exhibited in vivo with appropriate models of multiple sclerosis and cancer.
摘要翻译： 本发明提供包含稳定包封在脂质体中的糖皮质激素或糖皮质激素衍生物的药物组合物。 糖皮质激素或糖皮质激素衍生物选自pKa等于或低于11的两亲性弱碱性糖皮质激素或糖皮质激素衍生物，在pH7的logD在-2.5和1.5之间的范围内; 或pKa高于3.5的两亲性弱酸GC或GC衍生物，pH7的logD在-2.5和1.5之间的范围内。 用适当的多发性硬化症和癌症模型在体内展示本发明的药物组合物的治疗效果。
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公开(公告)号：US4797285A
公开(公告)日：1989-01-10
申请号：US806084
申请日：1985-12-06
CPC分类号： A61K9/127 , A61K31/70 , Y10T428/2984
摘要： A drug/liposome composition comprising an aqueous suspension of liposomes and, entrapped in the lipid bilayer region of the liposomes, an anthraquinone drug containing quinone and hydroquinone functionalities on adjacent anthracene rings. An iron-specific trihydroxamic chelating agent contained in the bulk aqueous phase of the suspension and a lipophilic free-radical scavenger contained in the bilayer region of the liposome cooperate to reduce chemical modification of both drug and lipid components of the composition. A preferred composition containing doxorubicin and alpha-tocopherol entrapped in the liposomes, and ferrioxamine in the aqueous suspension phase is effective in treating human neoplasms, with significantly reduced side effects over those produced by free-drug administration.
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公开(公告)号：US4920016A
公开(公告)日：1990-04-24
申请号：US132136
申请日：1987-12-18
申请人： Theresa M. Allen , Alberto Gabizon
发明人： Theresa M. Allen , Alberto Gabizon
CPC分类号： A61K9/1271 , Y10S436/829 , Y10S514/885 , Y10T428/2984
摘要： A composition of liposomes which contain an entrapped pharmaceutical agent and are characterized by (a) liposome sizes predominantly between about 0.07 and 0.5 microns; (b) at least about 50 mole percent of a membrane-rigidifying lipid, such as sphingomyelin or neutral phospholipids with predominantly saturated acyl chains; and (c) between about 5-20 mole percent of a glycolipid selected from the group consisting of ganglioside GM.sub.1, saturated phosphatidylinositol, and monogalactosyl stearate. The liposomes show high blood/RES tissue distribution ratios, and are effective for drug administration to tumors via intravenous drug delivery.
摘要翻译： 脂质体的组合物，其含有截留的药剂，其特征在于（a）主要在约0.07和0.5微米之间的脂质体大小; （b）至少约50摩尔％的膜 - 硬化脂质，例如主要具有饱和酰基链的鞘磷脂或中性磷脂; 和（c）约5-20摩尔％的选自神经节苷脂GM1，饱和磷脂酰肌醇和单半乳糖基硬脂酸酯的糖脂。 脂质体显示高血/ RES组织分布比例，并且通过静脉内药物递送对肿瘤的药物给药是有效的。
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公开(公告)号：US4898735A
公开(公告)日：1990-02-06
申请号：US256844
申请日：1988-10-12
IPC分类号： A61K9/127
CPC分类号： A61K31/70 , A61K9/127 , Y10T428/2982
摘要： A drug/liposome composition comprising an aqueous suspension of liposomes and, entrapped in the lipid bilayer region of the liposomes, an anthraquinone drug containing quinone and hydroquinone functionalities on adjacent anthracene rings. An iron-specific trihydroxamic chelating agent contained in the bulk aqueous phase of the suspension and a lipophilic free-radical scavenger contained in the bilayer region of the liposome cooperate to reduce chemical modification of both drug and lipid components of the composition. A preferred composition containing doxorubicin and alpha-tocopherol entrapped in the liposomes, and ferrioxamine in the aqueous suspension phase is effective in treating human neoplasms, with significantly reduced side effects over those produced by free-drug administration.
摘要翻译： 一种药物/脂质体组合物，其包含脂质体的水性悬浮液，并且包埋在脂质体的脂质双层区域中，在相邻的蒽环上含有醌和氢醌官能团的蒽醌药物。 包含在悬浮液的本体水相中的铁特异性三羟肟酸螯合剂和包含在脂质体的双层区域中的亲脂性自由基清除剂配合以减少组合物的药物和脂质组分的化学修饰。 包含在脂质体中的多柔比星和α-生育酚的优选组合物和含水悬浮相中的铁草胺在治疗人类肿瘤方面是有效的，与通过游离药物给药产生的副作用相比显着降低。
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