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31. 发明申请

WO2013008240A8 LIPOSOMES CO-ENCAPSULATING A BISPHOSPHONATE AND AN AMPHIPATHIC AGENT 审中-公开
标题翻译：合成双磷酸盐和活性成分的脂质体
公开(公告)号：WO2013008240A8
公开(公告)日：2013-03-07
申请号：PCT/IL2012050249
申请日：2012-07-12
申请人： YISSUM RES DEV CO , SHAARE ZEDEK MEDICAL CT , GABIZON ALBERTO A , BARENHOLZ YECHEZKEL , SHMEEDA HILARY
发明人： GABIZON ALBERTO A , BARENHOLZ YECHEZKEL , SHMEEDA HILARY
IPC分类号： A61K9/127 , A61K31/663 , A61K31/704
CPC分类号： A61K9/127 , A61K9/1271 , A61K9/1278 , A61K31/663 , A61K31/704 , A61K35/15 , A61K35/17 , A61K38/2013 , A61K38/2026 , A61K38/2086 , A61K45/06 , A61K47/551 , A61K47/6911 , A61K2039/5158 , A61K2039/55555 , A61K2300/00
摘要： The present disclosure provides liposomes comprising a membrane and an intrahposomal aqueous water phase, the membrane comprising at least one liposome forming lipid and the intrahposomal aqueous water phase comprises a salt of a bisphosphonate together with an amphipathic weak base agent (PLAD). An example of a liposome is one comprising co encapsulated in the intrahposomal aqueous water phaseN-containing bisphosphonate, such as alendronate, and an anthracycline such as doxorubicin which was shown to increase survival as compared to Doxil or to administrations of liposomal alendronate (PLA) and Doxil (separate liposomes). Such liposomes may carry a targeting moiety exposed at the liposome's outer surface, for example, conjugate of folic acid as a targeting moiety to folate receptor (FT-PLAD). Also provided by the present disclosure is a method of preparing the liposomes and methods of use of the liposomes, at times, in combination with additional active ingredients, such as ?d T-cells.
摘要翻译：本公开提供了包含膜和片内水性水相的脂质体，所述膜包含至少一种形成脂质体的脂质，并且所述体内水性水相包含双膦酸盐与两亲性弱碱性试剂（PLAD）。脂质体的实例是包被在包含在含有盐水的双膦酸盐例如阿仑膦酸钠和诸如阿霉素的蒽环类中的嵌合体水包油水相，其与Doxil相比显示增加存活，或者与脂质体阿仑膦酸盐（PLA）和 Doxil（单独的脂质体）。这样的脂质体可以携带在脂质体的外表面暴露的靶向部分，例如作为叶酸受体（FT-PLAD）的靶向部分的叶酸的缀合物。本公开还提供了制备脂质体的方法和脂质体的使用方法，有时与另外的活性成分如βdT细胞组合。

32. 发明申请

WO2010041256A2 A COMPOSITION OF MATTER COMPRISING LIPOSOMES EMBEDDED IN A POLYMERIC MATRIX AND METHODS OF USING SAME 审中-公开
标题翻译：包含嵌入在聚合物基质中的脂质体的成分的组合物及其使用方法
公开(公告)号：WO2010041256A2
公开(公告)日：2010-04-15
申请号：PCT/IL2009000967
申请日：2009-10-11
申请人： YISSUM RES DEV CO , BARENHOLZ YECHEZKEL , COHEN RIVKA
发明人： BARENHOLZ YECHEZKEL , COHEN RIVKA
IPC分类号： A61K9/127 , A61K9/16 , A61K31/445
CPC分类号： A61K9/127 , A61K31/445 , A61K31/573
摘要： The present disclosure provides a composition of matter comprising liposomes encapsulating in their intraliposomal aqueous compartment at least one active agent, the liposomes having a diameter of at least 200nm and being embedded in a water insoluble, water absorbed cross-linked polymeric matrix. In one embodiment, the composition of matter is held within an aqueous medium, preferably being in iso-osmotic equilibrium with the intraliposomal aqueous compartments of the liposomes. The present disclosure also provides a method of removal of non-encapsulated active agent from the composition of matter, a method of preparing said composition of matter, a pharmaceutical composition comprising said composition of matter, use of such composition of matter; a method of providing prolonged delivery of a active agent to a subject in need thereof by administering to said subject the composition of matter disclosed herein as well as a package comprising said composition of matter held within said aqueus medium and instructions for use thereof.
摘要翻译：本公开提供了一种包含在其脂质体内水性隔室中包封至少一种活性剂的脂质体的物质组合物，所述脂质体具有至少200nm的直径并且嵌入在水不溶性的吸水交联聚合物基质中。在一个实施方案中，物质组合物保持在水性介质中，优选与脂质体的脂质体内水性隔室处于等渗平衡。本公开还提供了从物质组合物中除去未包封的活性剂的方法，制备所述物质组合物的方法，包含所述组合物的药物组合物，所述物质组合物的使用; 通过向所述受试者施用本文公开的物质的组合物以及包含所述组合物的包装，所述组合物保持在所述aqueus培养基内以及使用说明书，提供活性剂向有需要的受试者的延长递送的方法。

33. 发明申请

WO2009072136A1 PARTICULATE DRUG CARRIERS AS DESENSITIZING AGENTS 审中-公开
标题翻译：颗粒状药物作为脱敏剂
公开(公告)号：WO2009072136A1
公开(公告)日：2009-06-11
申请号：PCT/IL2008/001591
申请日：2008-12-07
申请人： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM , THE BAY ZOLTAN FOUNDATION FOR APPLIED RESEARCH , FACULTY OF MEDICINE OF SEMMELWEIS UNIVERSITY , BARENHOLZ, Yechezkel , SZEBENI, Janos , TOTH, Miklos , ROSIVALL, Laszlo
发明人： BARENHOLZ, Yechezkel , SZEBENI, Janos , TOTH, Miklos , ROSIVALL, Laszlo
IPC分类号： A61K47/48 , A61P37/02
CPC分类号： A61K9/0019 , A61K9/1271 , A61K31/337 , A61K31/475 , A61K31/555 , A61K31/704
摘要： The present invention provides methods for desensitization for prevention or diminishing hypersensitivity reactions including C activation-related pseudoallergy (CARPA) and other reactions to particulate medicines. The desensitization is performed via pretreatment using a drug-free vehicle or carrier to eliminate or diminish the clinical symptoms of hypersensitivity.
摘要翻译：本发明提供了用于预防或减少包括C活化相关假性反应（CARPA）和其他对颗粒药物的反应的超敏反应的脱敏的方法。通过使用无药物载体或载体的预处理来进行脱敏以消除或减少超敏反应的临床症状。

34. 发明申请

WO2007066335A3 METHODS FOR AFFECTING LIPOSOME COMPOSITION BY ULTRASOUND IRRADIATION 审中-公开
标题翻译：通过超声波辐射影响脂质体组合物的方法
公开(公告)号：WO2007066335A3
公开(公告)日：2008-07-10
申请号：PCT/IL2006001404
申请日：2006-12-07
申请人： YISSUM RES DEV CO , UNIV BEN GURION , BARENHOLZ YECHEZKEL , SCHROEDER AVI , KOST JOSEPH
发明人： BARENHOLZ YECHEZKEL , SCHROEDER AVI , KOST JOSEPH
IPC分类号： A61K9/00 , A61K9/127 , A61K47/48
CPC分类号： A61K41/0028 , A61K9/127 , A61K9/1271 , A61K9/1277
摘要： The present invention provides methods for loading of agents and substances into per-formed liposomes, preferably a suspension of pre-formed liposomes as well as to methods for the controlled quantum (step-wise) release of agents and substances from liposomes. One of the principle features of the methods of the invention is to expose the liposomes to ultrasound irradiation having predefined parameters, resulting in an increase in permeability of the liposomes, thereby permitting, respectively, the loading and/or release of agents and substances into and/or from the liposomes.
摘要翻译：本发明提供了将试剂和物质装载到成形的脂质体中，优选预先形成的脂质体的悬浮液以及从脂质体中受控量子（逐步）释放试剂和物质的方法。本发明方法的主要特征之一是将脂质体暴露于具有预定参数的超声辐照，导致脂质体的渗透性增加，从而分别允许试剂和物质的加载和/或释放进入和 /或从脂质体。

35. 发明申请

WO2007049278A3 A METHOD FOR PREPARING LIPOSOMES AND USES THEREOF 审中-公开
标题翻译：制备脂质体的方法及其用途
公开(公告)号：WO2007049278A3
公开(公告)日：2007-09-13
申请号：PCT/IL2006001229
申请日：2006-10-26
申请人： YISSUM RES DEV CO , UNIV NEW YORK , BARENHOLZ YECHEZKEL , GARBUZENKO OLGA , BARHUM KEREN , GRANT GILBERT , PISKOUN BORIS
发明人： BARENHOLZ YECHEZKEL , GARBUZENKO OLGA , BARHUM KEREN , GRANT GILBERT , PISKOUN BORIS
IPC分类号： A61K9/127
CPC分类号： A61K9/127 , A61K9/1277
摘要： The present invention provides a simplified and cost effective method preparing liposomes, the method comprising providing a dry liposome forming lipid or a dry mixture comprising a liposome forming lipid; dissolving the liposome forming lipid or said mixture comprising a liposome forming lipid of step (a) with a protic organic solvent to form a solution or dispersion of said lipid; and adding the solution or dispersion of step (b) to ions containing aqueous solution to form a liposome suspension; wherein the liposomes are capable of encapsulating an agent at a ratio between the agent and the liposome forming lipid being greater than 1.0. The method is characterized in that it does not involve drying the solution or dispersion to form a dry lipid film; and/or down-sizing liposomes in said liposome suspension to form small unilamellar vesicles (SUV). The thus formed liposomes may then be used for loading thereto an active agent, such as amphiphatic weak acid/base drugs.
摘要翻译：本发明提供了制备脂质体的简化且成本有效的方法，该方法包括提供形成脂质体的干脂质体或包含形成脂质体的脂质的干混合物; 将形成脂质体的脂质或包含步骤（a）的脂质体形成脂质的所述混合物与质子有机溶剂一起溶解以形成所述脂质的溶液或分散体; 并将步骤（b）的溶液或分散体加入到含有水溶液的离子中以形成脂质体悬浮液; 其中所述脂质体能够以所述药剂和形成脂质体的脂质之间的比率包封药剂，其大于1.0。该方法的特征在于它不涉及干燥溶液或分散体以形成干脂膜; 和/或缩小所述脂质体悬浮液中的脂质体以形成小单层囊泡（SUV）。这样形成的脂质体然后可用于向其加载活性剂，例如两性弱酸/碱性药物。

36. 发明申请

WO2005046643A2 METHOD FOR DRUG LOADING IN LIPOSOMES 审中-公开
标题翻译：在脂质体中加载药物的方法
公开(公告)号：WO2005046643A2
公开(公告)日：2005-05-26
申请号：PCT/IL2004/001041
申请日：2004-11-14
申请人： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM , BARENHOLZ, Yechezkel , GABIZON, Alberto A.
发明人： BARENHOLZ, Yechezkel , GABIZON, Alberto A.
IPC分类号： A61K9/127
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 disclosed. 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：公开了一种脂质体组合物，其具有以葡萄糖醛酸盐阴离子与盐形式包载的可质子治疗剂。还公开了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。在可质子化试剂是阿霉素的一个实施方案中，本发明的方法具有可比较的负载效率，更快的释放速率，与用具有硫酸盐作为抗衡离子的铵离子梯度负载相比，不会损害治疗效果。

37. 发明申请

WO2003017998A1 PLATINUM COMPLEXES AND THEIR USE IN CANCER TREATMENT 审中-公开
标题翻译：铂络合物及其在癌症治疗中的用途
公开(公告)号：WO2003017998A1
公开(公告)日：2003-03-06
申请号：PCT/IL2002/000687
申请日：2002-08-21
申请人： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM , BARENHOLZ, Yechezkel , GIBSON, Dan , NAJAJREH, Yousef , KHAZANOV, Elena
发明人： BARENHOLZ, Yechezkel , GIBSON, Dan , NAJAJREH, Yousef , KHAZANOV, Elena
IPC分类号： A61K31/28
CPC分类号： C07F15/0093
摘要： The present invention concerns novel platinum complexes in which at least one of the amine ligand is a non-planar heterocyclic aliphatic amine. The platinum complexes may be in a trans or cis configuration and were found to posses therapeutic activites. Thus, the present concerns novel platinum complexes, pharmaceutical compositions comprising them and other uses thereof.
摘要翻译：本发明涉及新的铂络合物，其中至少一个胺配体是非平面杂环脂族胺。铂络合物可能处于反式或顺式构型并被发现具有治疗活性。因此，本发明涉及新型铂络合物，包含它们的药物组合物及其其它用途。

38. 发明申请

WO2002064110A2 CAROTENOID-LOADED LIPOSOMES 审中-公开
标题翻译： CAROTENOID装载脂质体
公开(公告)号：WO2002064110A2
公开(公告)日：2002-08-22
申请号：PCT/IB2002/000417
申请日：2002-02-13
申请人： YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM , BARENHOLZ, Yechezkel , DIMINSKY, Dvorah , COHEN, Rivka
发明人： BARENHOLZ, Yechezkel , DIMINSKY, Dvorah , COHEN, Rivka
IPC分类号： A61K9/00
CPC分类号： A61K9/127 , A61K8/14 , A61K8/31 , A61K31/01 , A61K31/015 , A61K31/045 , A61K31/047 , A61K31/122 , A61K2800/522 , A61Q17/00 , A61Q17/04 , A61Q19/00
摘要： The present invention is based on a novel method for encapsulating in liposomes substantialy water immiscible carotenoids. Therefore, there are provided by the present invention formulations comprising liposomes loaded with an amount of at least one water immiscible carotenoid. Pharmaceutical compositions comprising such a formulation, and a method for preparing the liposomes loaded with said carotenoid.
摘要翻译：本发明是基于一种用于将脂质体封装在大体上与水不混溶的类胡萝卜素的新方法。因此，本发明提供的制剂包含负载量至少一种与水不混溶的类胡萝卜素的脂质体。包含这种制剂的药物组合物，以及用于制备负载有所述类胡萝卜素的脂质体的方法。

39. 发明申请

WO0159156A3 DETECTION OF BINDING OF CHARGED SPECIES USING pH- OR POTENTIAL-SENSITIVE PROBES 审中-公开
标题翻译：使用pH或潜在敏感探针检测充电物种的结合
公开(公告)号：WO0159156A3
公开(公告)日：2002-03-28
申请号：PCT/IL0100134
申请日：2001-02-09
申请人： YISSUM RES DEV CO , BARENHOLZ YECHEZKEL , HIRSCH LERNER DANIELLE , COHEN RIVKA , DAGAN ARIE , GATT SHIMON
发明人： BARENHOLZ YECHEZKEL , HIRSCH-LERNER DANIELLE , COHEN RIVKA , DAGAN ARIE , GATT SHIMON
IPC分类号： C12Q1/68 , G01N33/543 , G01N33/58 , G01N33/92 , C07D311/16
CPC分类号： G01N33/92 , C12Q1/6804 , G01N33/5432 , G01N33/582 , G01N2405/04 , C12Q2563/179 , C12Q2527/119
摘要： The extent of binding of a moiety, such as a biomolecule, to a surface, where the local environment at the surface has a pH or surface potential which is altered upon binding of the moiety, is determined by stably incorporating at the surface a probe which contains a pH- or potential-sensitive fluorophore.
摘要翻译：通过在表面上稳定地并入表面，确定表面上的局部环境具有在部分结合时被改变的pH或表面电位的表面上的部分（例如生物分子）与表面结合的程度，含有pH或潜在敏感的荧光团。

40. 发明申请

WO9939736A3 DELIVERY OF IMMUNOGENIC MOLECULES VIA HBsAg PARTICLES 审中-公开
标题翻译：通过HBsAg颗粒递送免疫分子
公开(公告)号：WO9939736A3
公开(公告)日：1999-09-23
申请号：PCT/IL9900060
申请日：1999-01-29
申请人： YISSUM RES DEV CO , REIMANN JORG , BARENHOLZ YECHEZKEL , DIMINSKY DVORAH , SCHIRMBECK REINHOLD
发明人： REIMANN JORG , BARENHOLZ YECHEZKEL , DIMINSKY DVORAH , SCHIRMBECK REINHOLD
IPC分类号： A61K38/00 , A61K31/7088 , A61K39/00 , A61K39/085 , A61K39/106 , A61K39/21 , A61K39/29 , A61K39/385 , A61K39/39 , A61P37/02 , A61P37/04 , A61K38/19
CPC分类号： A61K39/21 , A61K39/12 , A61K39/292 , A61K2039/5256 , A61K2039/5258 , A61K2039/545 , A61K2039/55522 , A61K2039/55555 , A61K2039/55561 , A61K2039/57 , C12N2730/10134 , C12N2740/16134 , A61K2300/00
摘要： Compositions of HBsAg particles having biologically active molecules contained in the particles, and methods of their use, e.g. in stimulating enhanced immune responses, are described. Antigenic peptides contained in HBsAg particles were found to produce a CTL response where none was elicited by the peptide alone. Encapsulation of immunostimulating molecules, such as cytokines, greatly enhanced the CTL response evoked by the HBsAg particles themselves.
摘要翻译：包含在颗粒中的具有生物活性分子的HBsAg颗粒的组合物及其使用方法，例如，在刺激增强的免疫应答方面。发现包含在HBsAg颗粒中的抗原肽产生CTL反应，其中没有一个被单独引发。免疫刺激分子如细胞因子的封装大大增强了HBsAg颗粒本身诱发的CTL反应。

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