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    METHOD FOR ADMINISTRATION OF PEGYLATED LIPOSOMAL DOXORUBICIN
    5.
    发明申请
    METHOD FOR ADMINISTRATION OF PEGYLATED LIPOSOMAL DOXORUBICIN 审中-公开
    聚乙二醇脂多糖的施用方法

    公开(公告)号：US20120288558A1

    公开(公告)日：2012-11-15

    申请号：US13552433

    申请日：2012-07-18

    申请人： Alberto A. Gabizon

    发明人： Alberto A. Gabizon

    IPC分类号： A61K9/127 ,  A61P35/00 ,  A61K31/704

    CPC分类号： A61K31/337 ,  A61K9/1271

    摘要： An embodiment of the present invention comprises a method of treating malignancies in a subject in need of treatment comprising administering to the subject a high loading dose of a pegylated liposomal doxorubicin (PLD) in an initial cycle, followed by a reduced dose in a second cycle, wherein the second cycle reduced dose is in the range of 20% to 50%, preferably 50%, of the initial loading dose, and thereafter one or more maintenance doses in further cycles. The interval between dose cycles is in the range of about three-to-four weeks, preferably about four weeks. The initial loading dose is in the range of between the maximum tolerated dose (MTD) and the recommended dose, preferably the MTD (for instance, in the range of about 70 mg/m2 to 50 mg/m2, preferably 60 mg/m2). The one or more maintenance doses are in the range of about 40 mg/m2 to 50 mg/m2, preferably 45 mg/m2).

    摘要翻译： 本发明的一个实施方案包括治疗需要治疗的受试者中的恶性肿瘤的方法，其包括在初始循环中向受试者施用高负荷剂量的聚乙二醇化脂质体多柔比星（PLD），随后在第二周期中给予减少的剂量 ，其中所述第二循环减量剂量在初始负荷剂量的20％至50％，优选50％的范围内，此后在另外的循环中进行一次或多次维持剂量。 剂量循环之间的间隔在约3至4周的范围内，优选约4周。 初始加载剂量在最大耐受剂量（MTD）和推荐剂量之间的范围内，优选MTD（例如，在约70mg / m 2至50mg / m 2，优选60mg / m 2）的范围内， 。 一个或多个维持剂量在约40mg / m 2至50mg / m 2，优选45mg / m 2的范围内）。

    METHOD FOR ADMINISTRATION OF PEGYLATED LIPOSOMAL DOXORUBICIN
    6.
    发明申请
    METHOD FOR ADMINISTRATION OF PEGYLATED LIPOSOMAL DOXORUBICIN 审中-公开
    聚乙二醇脂多糖的施用方法

    公开(公告)号：US20100297216A1

    公开(公告)日：2010-11-25

    申请号：US12517864

    申请日：2007-01-21

    申请人： Alberto A. Gabizon

    发明人： Alberto A. Gabizon

    IPC分类号： A61K9/127 ,  A61K31/35

    CPC分类号： A61K31/337 ,  A61K9/1271

    摘要： An embodiment of the present invention comprises a method of treating malignancies in a subject in need of treatment comprising administering to the subject a high loading dose of a pegylated liposomal doxorubicin (PLD) in an initial cycle, followed by a reduced dose in a second cycle, wherein the second cycle reduced dose is in the range of 20% to 50%, preferably 50%, of the initial loading dose, and thereafter one or more maintenance doses in further cycles. The interval between dose cycles is in the range of about three-to-four weeks, preferably about four weeks. The initial loading dose is in the range of between the maximum tolerated dose (MTD) and the recommended dose, preferably the MTD (for instance, in the range of about 70 mg/m2 to 50 mg/m2, preferably 60 mg/m2). The one or more maintenance doses are in the range of about 40 mg/m2 to 50 mg/m2, preferably 45 mg/m2).

    摘要翻译： 本发明的一个实施方案包括治疗需要治疗的受试者中的恶性肿瘤的方法，其包括在初始循环中向受试者施用高负荷剂量的聚乙二醇化脂质体多柔比星（PLD），随后在第二周期中给予减少的剂量 ，其中所述第二循环减量剂量在初始负荷剂量的20％至50％，优选50％的范围内，此后在另外的循环中进行一次或多次维持剂量。 剂量循环之间的间隔在约3至4周的范围内，优选约4周。 初始加载剂量在最大耐受剂量（MTD）和推荐剂量之间的范围内，优选MTD（例如，在约70mg / m 2至50mg / m 2，优选60mg / m 2）的范围内， 。 一个或多个维持剂量在约40mg / m 2至50mg / m 2，优选45mg / m 2的范围内）。

    Combined chemo-immunotherapy with liposomal drugs and cytokines
    7.
    发明授权
    Combined chemo-immunotherapy with liposomal drugs and cytokines 失效
    联合化疗免疫治疗与脂质体药物和细胞因子

    公开(公告)号：US06787132B1

    公开(公告)日：2004-09-07

    申请号：US09555674

    申请日：2000-08-03

    申请人： Alberto A. Gabizon ,  Eliezer Kedar ,  Yechezkel Barenholz

    发明人： Alberto A. Gabizon ,  Eliezer Kedar ,  Yechezkel Barenholz

    IPC分类号： A61K3819

    CPC分类号： A61K38/21 ,  A61K9/1271 ,  A61K38/193 ,  A61K38/20 ,  A61K38/2013 ,  A61K2300/00

    摘要： A method of antitumor therapy is described in which administration of a chemotherapeutic drug, encapsulated in liposomes, is supplemented by administration of an immunostimulating cytokine. The cytokine is preferably also encapsulated in liposomes. In tumor models for lung and colon carcinomas, this method produced a significantly greater therapeutic effect, as evidenced by survival rate and tumor size, than a combination of the effects produced by the free or liposome-encapsulated components administered individually.

    摘要翻译： 描述了一种抗肿瘤治疗方法，其中通过施用免疫刺激性细胞因子补充了包封在脂质体中的化疗药物的施用。 细胞因子优选也包封在脂质体中。 在肺和结肠癌的肿瘤模型中，与单独施用的游离或脂质体包封的组分产生的效果的组合相比，该方法产生了显着更大的治疗效果，如存活率和肿瘤大小所证明的。

    LIPOSOMES CO-ENCAPSULATING A BISPHOSPHONATE AND AN AMPHIPATHIC AGENT
    8.
    发明申请
    LIPOSOMES CO-ENCAPSULATING A BISPHOSPHONATE AND AN AMPHIPATHIC AGENT 有权
    合成双磷酸盐和活性成分的脂质体

    公开(公告)号：US20140328899A1

    公开(公告)日：2014-11-06

    申请号：US14232332

    申请日：2012-07-07

    申请人： Alberto A. Gabizon ,  Yechezkel Barenholz ,  Hilary Shmeeda

    发明人： Alberto A. Gabizon ,  Yechezkel Barenholz ,  Hilary Shmeeda

    IPC分类号： A61K9/127 ,  A61K31/663 ,  A61K31/704 ,  A61K35/14

    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 intraliposomal aqueous water phase, the membrane comprising at least one liposome forming lipid and the intraliposomal 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 intraliposomal aqueous water phase N-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 γδ T-cells.

    摘要翻译： 本公开提供了包含膜和脂质体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和脂质体内水性水相，其包含双膦酸盐与两亲性弱碱性试剂（PLAD）。 脂质体的一个例子是包被在包含在脂质体内水相N含量的二膦酸盐（例如阿仑膦酸盐）和蒽环类霉素（如多柔比星）中的共聚物，其显示与Doxil相比增加了存活，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γδT细胞组合。

    Liposomal compositions of glucocorticoid and glucocorticoid derivatives
    9.
    发明授权
    Liposomal compositions of glucocorticoid and glucocorticoid derivatives 有权
    糖皮质激素和糖皮质激素衍生物的脂质体组成

    公开(公告)号：US08932627B2

    公开(公告)日：2015-01-13

    申请号：US11662172

    申请日：2005-09-11

    申请人： Yechezkel Barenholz ,  Alberto A. Gabizon ,  Yuval Avnir

    发明人： Yechezkel Barenholz ,  Alberto A. Gabizon ,  Yuval Avnir

    IPC分类号： A61K9/127 ,  A61K31/573

    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。

    TARGETED LIPOSOMES COMPRISING N-CONTAINING BISPHOSPHONATES AND USES THEREOF
    10.
    发明申请
    TARGETED LIPOSOMES COMPRISING N-CONTAINING BISPHOSPHONATES AND USES THEREOF 审中-公开
    包含含N的二硫代磷酸酯的目标药物及其用途

    公开(公告)号：US20120100206A1

    公开(公告)日：2012-04-26

    申请号：US13377629

    申请日：2010-06-10

    申请人： Hilary Shmeeda ,  Alberto A. Gabizon

    发明人： Hilary Shmeeda ,  Alberto A. Gabizon

    IPC分类号： A61K9/127 ,  A61K31/675 ,  A61P19/10 ,  A61K31/663

    CPC分类号： A61K31/663 ,  A61K9/0095 ,  A61K9/127 ,  A61K9/1271 ,  A61K9/1272 ,  A61K9/1273 ,  A61K47/6911

    摘要： The present is based on the finding that folate targeted liposomal alendronate (FT-AL-L) was significantly more potent against two tested cancer cell lines than the free alendronate (AL) or the non-targeted liposomal alendronate (AL-L), as observed by the increased cytotoxicity of the folate targeted liposomal alendronate. Thus, the present disclosure provides targeted liposomes comprising a membrane and an intraliposomal core, the membrane comprising at least one liposome forming lipid and a targeting moiety, such as folate, exposed at the membrane's outer surface; and the intraliposomal core comprising encapsulated therein least one N-containing bisphosphonate. Also provided by the present disclosure are methods of use of the targeted liposomes such as for the treatment of a disease or disorder.

    摘要翻译： 本发明基于以下发现：叶酸盐靶向脂质体阿仑膦酸盐（FT-AL-L）对于两种测试的癌细胞系比游离的阿仑膦酸钠（AL）或非靶向脂质体阿仑膦酸盐（AL-L）显着更有效，如 通过叶酸盐靶向脂质体阿仑膦酸盐的增加的细胞毒性观察到。 因此，本公开提供了包含膜和脂质体内核的靶向脂质体，所述膜包含至少一种形成脂质体的脂质和在膜的外表面暴露的靶向部分，例如叶酸盐; 和包含至少一种含N的双膦酸盐的脂质体内核心。 本公开还提供了使用靶向脂质体的方法，例如用于治疗疾病或病症。