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1. 发明申请

WO2015175866A1 USE OF BISPHOSPHONATES AS HIV/AIDS ADJUNCTIVE TREATMENT 审中-公开
标题翻译：使用双膦酸酯作为艾滋病毒/艾滋病的ADJUNCTIVE TREATMENT
公开(公告)号：WO2015175866A1
公开(公告)日：2015-11-19
申请号：PCT/US2015/030952
申请日：2015-05-15
申请人： BIOREST LTD. , OREGON HEALTH & SCIENCE UNIVERSITY
发明人： RICHTER, Yoram , GOLOMB, Gershon , SACHA, Jonah, B.
IPC分类号： A61K31/663 , A61K9/00 , A61K9/127 , A61K9/16 , A61P31/18
CPC分类号： A61K31/663 , A61K9/0019 , A61K9/127 , A61K9/5153 , A61K31/675 , A61K45/06 , A61K47/24
摘要： The present invention relates to use of bisphosphonate formulations for the treatment and management of HIV/ AIDS. The method of the invention comprises administering a formulation comprising an effective amount of a bisphosphonate that specifically inhibits the activity and/or decreases the number of monocytes and/or macrophages, thereby reducing or eliminating HIV reservoirs. The invention also provides a method of complementing an HIV antiviral therapy, such as the highly active antiretroviral therapy (HAART), with a bisphosphonate formulation to improve clinical outcome.
摘要翻译：本发明涉及双膦酸盐制剂用于治疗和管理艾滋病毒/艾滋病的用途。本发明的方法包括施用包含有效量的双膦酸盐的制剂，其特异性抑制活性和/或减少单核细胞和/或巨噬细胞的数量，从而减少或消除HIV储库。本发明还提供了一种补充HIV抗病毒治疗（例如高活性抗逆转录病毒治疗（HAART））与双膦酸盐制剂以改善临床结果的方法。

2. 发明申请

WO2005044175A2 DESENSITIZATION OF COMPLEMENT ACTIVATION USING MONOCYTE/MACROPHAGE INHIBITORY COMPOUNDS 审中-公开
标题翻译：利用单细胞/巨噬细胞抑制化合物灭活补体激活
公开(公告)号：WO2005044175A2
公开(公告)日：2005-05-19
申请号：PCT/IB2004/003620
申请日：2004-11-05
申请人： BIOREST LTD. , GOLOMB, Gershon , EPSTEIN, Hila
发明人： GOLOMB, Gershon , EPSTEIN, Hila
IPC分类号： A61K
CPC分类号： A61K31/663 , A61K9/127
摘要： The present invention relates to methods and compositions designed for the prevention, reduction, treatment, or management of complement activation-related acute hypersensitivity also known as C-mediated pseudoallergy (CARPA) that results from the administration of a medicinal composition including, but not limited to, those compositions in liposomal, micellar, nanoparticle, emulsion, and colloidal formulations. The methods of the invention comprise the administration of an effective amount of one or more therapeutic agents containing one or more active compounds which specifically decreases or inhibits the activity of and/or eliminates or diminishes the amount of macrophages and/or monocytes. In preferred embodiments, the active compound is a bisphosphonate.
摘要翻译：本发明涉及设计用于预防，减少，治疗或控制补体激活相关的急性超敏反应的方法和组合物，所述超敏反应也称为C介导的假性过敏（CARPA），其由施用药物组合物，包括但不限于脂质体，胶束，纳米颗粒，乳剂和胶体制剂中的那些组合物。本发明的方法包括施用有效量的一种或多种含有一种或多种活性化合物的治疗剂，所述活性化合物特异性降低或抑制巨噬细胞和/或单核细胞的活性和/或消除或减少巨噬细胞和/或单核细胞的量。在优选的实施方案中，活性化合物是双膦酸盐。

3. 发明申请

WO2005013948A2 METHOD OF TREATING ACUTE MYOCARDIAL INFARCTION 审中-公开
标题翻译：治疗急性心肌梗塞的方法
公开(公告)号：WO2005013948A2
公开(公告)日：2005-02-17
申请号：PCT/US2004/020536
申请日：2004-06-24
申请人： BIOREST LTD. , EDELMAN, Elazer, R. , GOLOMB, Gershon , DANENBERG, Haim, D.
发明人： EDELMAN, Elazer, R. , GOLOMB, Gershon , DANENBERG, Haim, D.
IPC分类号： A61K31/00
CPC分类号： A61K31/663 , A61K9/127 , A61K9/51 , A61K31/66 , A61K31/675
摘要： A method of treating an acute myocardial infarction by administering to an individual an effective amount of a formulation which inhibits and/or depletes phagocytic cells with high specificity, thereby suppressing the inflammatory response that occurs during and following acute myocardial infarction. The formulation comprises an agent which is an intracellular inhibitor that is released within the targeted phagocytic cells, specifically macrophage/monocytes, and inhibits and/or destroys the macrophages and/or monocytes, thereby reducing the final zone of infarct and improving cardiac repair and myocardial remodeling. Since macrophages and monocytes possess the unique ability to phagocytose large bodies, the agent is formulated into a specific size such that it can enter cells primarily via phagocytosis. Thus, the specifically sized formulation selectively targets monocytes/macrophages. The formulation may comprise an encapsulated agent, an embedded agent or a particulate agent, wherein the formulation is of a specific size, such that it can enter cells primarily via phagocytosis. The formulation is preferably in the size range of 0.03-1.0 microns.
摘要翻译：一种治疗急性心肌梗塞的方法，其通过向个体施用有效量的抑制和/或消除吞噬细胞的特异性高的制剂，由此抑制在急性心肌梗死期间和之后发生的炎性反应。该制剂包含作为靶向吞噬细胞特异性巨噬细胞/单核细胞释放的细胞内抑制剂的药剂，并且抑制和/或破坏巨噬细胞和/或单核细胞，从而减少梗塞的最后区域并改善心脏修复和心肌重塑。由于巨噬细胞和单核细胞具有吞噬大体的独特能力，所以将药物配制成特定的大小，使得其主要通过吞噬作用进入细胞。因此，特定尺寸的制剂选择性靶向单核细胞/巨噬细胞。制剂可以包括包封的试剂，嵌入剂或颗粒剂，其中所述制剂具有特定尺寸，使得其可以主要通过吞噬作用进入细胞。制剂优选在0.03-1.0微米的尺寸范围内。

4. 发明申请

WO2007012947A2 METHOD OF TREATING ISCHEMIA-REPERFUSION INJURY 审中-公开
标题翻译：治疗异位再灌注损伤的方法
公开(公告)号：WO2007012947A2
公开(公告)日：2007-02-01
申请号：PCT/IB2006/002028
申请日：2006-07-25
申请人： BIOREST LTD. , RICHTER, Yoram , EDELMAN, Elazer, R. , GOLOMB, Gershon , DANENBERG, Haim, D.
发明人： RICHTER, Yoram , EDELMAN, Elazer, R. , GOLOMB, Gershon , DANENBERG, Haim, D.
IPC分类号： A61K31/47
CPC分类号： A61K31/337 , A61K9/127 , A61K31/282 , A61K31/365 , A61K31/436 , A61K31/47 , A61K31/4745 , A61K31/513 , A61K31/56 , A61K31/60 , A61K31/616 , A61K31/663 , A61K31/7072 , A61K33/00 , A61K33/04 , A61K33/24
摘要： The present invention relates to methods and compositions designed for the prevention, reduction, treatment or management of ischemia-reperfusion injury. The methods of the invention comprise the administration of an effective amount of a therapeutic formulation containing one or more active compounds in a formulation which specifically decreases or inhibits the activity of and/or eliminates or diminishes the amount of phagocytic cells including, but not limited to, macrophages and/or monocytes. In preferred embodiments, the active compound is a bisphosphonate. The invention also provides pharmaceutical compositions of therapeutic formulations for administration to subjects currently suffering from, having recently suffered, or at risk of suffering from an ischemia-reperfusion injury.
摘要翻译：本发明涉及设计用于预防，减少，治疗或治疗缺血再灌注损伤的方法和组合物。本发明的方法包括在制剂中施用有效量的含有一种或多种活性化合物的治疗制剂，所述制剂特异性降低或抑制吞噬细胞的活性和/或消除或减少吞噬细胞的量，包括但不限于，巨噬细胞和/或单核细胞。在优选的实施方案中，活性化合物是双膦酸盐。本发明还提供了用于给予目前患有，最近遭受或有遭受缺血再灌注损伤风险的受试者的治疗制剂的药物组合物。

5. 发明申请

WO2005002545A1 METHOD OF TREATING ACUTE CORONARY SYNDROMES 审中-公开
标题翻译：治疗急性冠状动脉综合征的方法
公开(公告)号：WO2005002545A1
公开(公告)日：2005-01-13
申请号：PCT/US2004/020487
申请日：2004-06-24
申请人： BIOREST LTD. , RICHTER, Yoram , EDELMAN, Elazer, R. , GOLOMB, Gershon , DANENBERG, Haim, D.
发明人： EDELMAN, Elazer, R. , GOLOMB, Gershon , DANENBERG, Haim, D.
IPC分类号： A61K9/127
CPC分类号： A61K31/663
摘要： The present invention relates to methods and compositions designed for the treatment or management of acute coronary syndromes, particularly, unstable angina and acute myocardial infarction. The methods of the invention comprise the administration of an effective amount of a formulation containing one or more therapeutic agents which specifically decreases or inhibits the activity of phagocytic cells and/or eliminates or diminishes the amount of phagocytic cells including, but not limited to, macrophages and monocytes. The formulations are specifically targeted to phagocytic cells. The invention also provides pharmaceutical compositions of formulations containing one or more therapeutic agents of the invention for administration to subjects currently suffering from or having recently suffered an acture coronary syndrome such as unstable angina and acute myocardial infarction.
摘要翻译：本发明涉及设计用于治疗或治疗急性冠状动脉综合征，特别是不稳定性心绞痛和急性心肌梗塞的方法和组合物。本发明的方法包括施用有效量的含有一种或多种治疗剂的制剂，其特异性降低或抑制吞噬细胞的活性和/或消除或减少吞噬细胞的量，包括但不限于巨噬细胞和单核细胞。制剂专门针对吞噬细胞。本发明还提供了含有本发明的一种或多种治疗剂的制剂的药物组合物，用于给予目前患有或最近患有冠状动脉综合征如不稳定型心绞痛和急性心肌梗死的受试者。

6. 发明授权

EP1643982B1 METHOD OF TREATING ACUTE MYOCARDIAL INFARCTION 有权
标题翻译：方法急性心肌梗死的治疗
公开(公告)号：EP1643982B1
公开(公告)日：2015-09-23
申请号：EP04785964.0
申请日：2004-06-24
申请人： Biorest Ltd.
发明人： EDELMAN, Elazer, R. , GOLOMB, Gershon , DANENBERG, Haim, D.
IPC分类号： A61K31/00
CPC分类号： A61K31/663 , A61K9/127 , A61K9/51 , A61K31/66 , A61K31/675
摘要： A method of treating an acute myocardial infarction by administering to an individual an effective amount of a formulation which inhibits and/or depletes phagocytic cells with high specificity, thereby suppressing the inflammatory response that occurs during and following acute myocardial infarction. The formulation comprises an agent which is an intracellular inhibitor that is released within the targeted phagocytic cells, specifically macrophage/monocytes, and inhibits and/or destroys the macrophages and/or monocytes, thereby reducing the final zone of infarct and improving cardiac repair and myocardial remodeling. Since macrophages and monocytes possess the unique ability to phagocytose large bodies, the agent is formulated into a specific size such that it can enter cells primarily via phagocytosis.; Thus, the specifically sized formulation selectively targets monocytes/macrophages. The formulation may comprise an encapsulated agent, an embedded agent or a particulate agent, wherein the formulation is of a specific size, such that it can enter cells primarily via phagocytosis. The formulation is preferably in the size range of 0.03-1.0 microns.

7. 发明公开

EP1643982A2 METHOD OF TREATING ACUTE MYOCARDIAL INFARCTION 有权
标题翻译： VERFAHREN ZUR BEHANDLUNG VON AKUTEM MYOKARDINFARKT
公开(公告)号：EP1643982A2
公开(公告)日：2006-04-12
申请号：EP04785964.0
申请日：2004-06-24
申请人： Biorest Ltd.
发明人： EDELMAN, Elazer, R. , GOLOMB, Gershon , DANENBERG, Haim, D.
IPC分类号： A61K31/00
CPC分类号： A61K31/663 , A61K9/127 , A61K9/51 , A61K31/66 , A61K31/675
摘要： A method of treating an acute myocardial infarction by administering to an individual an effective amount of a formulation which inhibits and/or depletes phagocytic cells with high specificity, thereby suppressing the inflammatory response that occurs during and following acute myocardial infarction. The formulation comprises an agent which is an intracellular inhibitor that is released within the targeted phagocytic cells, specifically macrophage/monocytes, and inhibits and/or destroys the macrophages and/or monocytes, thereby reducing the final zone of infarct and improving cardiac repair and myocardial remodeling. Since macrophages and monocytes possess the unique ability to phagocytose large bodies, the agent is formulated into a specific size such that it can enter cells primarily via phagocytosis.; Thus, the specifically sized formulation selectively targets monocytes/macrophages. The formulation may comprise an encapsulated agent, an embedded agent or a particulate agent, wherein the formulation is of a specific size, such that it can enter cells primarily via phagocytosis. The formulation is preferably in the size range of 0.03-1.0 microns.
摘要翻译：一种治疗急性心肌梗塞的方法，其通过向个体施用有效量的抑制和/或消除吞噬细胞的特异性高的制剂，从而抑制在急性心肌梗死期间和之后发生的炎性反应。该制剂包含作为细胞内抑制剂的试剂，其在靶吞噬细胞内释放，特别是巨噬细胞/单核细胞，并且抑制和/或破坏巨噬细胞和/或单核细胞，从而减少梗塞的最后区域并改善心脏修复和心肌重塑。由于巨噬细胞和单核细胞具有吞噬大体的独特能力，所以将该药剂配制成特定的大小，使其能够主要通过吞噬作用进入细胞。因此，特定尺寸的制剂选择性靶向单核细胞/巨噬细胞。制剂可以包含包封的试剂，嵌入剂或颗粒剂，其中所述制剂具有特定尺寸，使得其可以主要通过吞噬作用进入细胞。制剂优选在0.03-1.0微米的尺寸范围内。

8. 发明公开

EP3142670A1 USE OF BISPHOSPHONATES AS HIV/AIDS ADJUNCTIVE TREATMENT 审中-公开
标题翻译： VERWENDUNG VON BISPHOSPHONATEN ALS ADJUNKTIVE HIV / AIDS-BEHANDLUNG
公开(公告)号：EP3142670A1
公开(公告)日：2017-03-22
申请号：EP15726814.5
申请日：2015-05-15
申请人： Biorest Ltd. , Oregon Health & Science University
发明人： RICHTER, Yoram , GOLOMB, Gershon , SACHA, Jonah, B.
IPC分类号： A61K31/663 , A61K9/00 , A61K9/127 , A61K9/16 , A61P31/18
CPC分类号： A61K31/663 , A61K9/0019 , A61K9/127 , A61K9/5153 , A61K31/675 , A61K45/06 , A61K47/24
摘要： The present invention relates to use of bisphosphonate formulations for the treatment and management of HIV/AIDS. The method of the invention comprises administering a formulation comprising an effective amount of a bisphosphonate that specifically inhibits the activity and/or decreases the number of monocytes and/or macrophages, thereby reducing or eliminating HIV reservoirs. The invention also provides a method of complementing an HIV antiviral therapy, such as the highly active antiretroviral therapy (HAART), with a bisphosphonate formulation to improve clinical outcome.
摘要翻译：本发明涉及二膦酸盐制剂用于治疗和管理艾滋病毒/艾滋病的用途。本发明的方法包括施用包含有效量的二膦酸盐的制剂，其特异性抑制活性和/或减少单核细胞和/或巨噬细胞的数量，从而减少或消除HIV储库。本发明还提供了一种补充HIV抗病毒治疗（例如高活性抗逆转录病毒治疗（HAART））与双膦酸盐制剂以改善临床结果的方法。

9. 发明授权

EP1638526B8 METHOD OF TREATING ACUTE CORONARY SYNDROMES 有权
标题翻译：方法急性冠脉综合征的治疗
公开(公告)号：EP1638526B8
公开(公告)日：2010-10-27
申请号：EP04756133.7
申请日：2004-06-24
申请人： Biorest Ltd.
发明人： EDELMAN, Elazer, R. , GOLOMB, Gershon , DANENBERG, Haim, D. , RICHTER, Yoram
IPC分类号： A61K9/127 , A61K31/663
CPC分类号： A61K31/663 , A61K9/127 , A61K9/51 , A61K31/66 , A61K31/675
摘要： A method of treating an acute myocardial infarction by administering to an individual an effective amount of a formulation which inhibits and/or depletes phagocytic cells with high specificity, thereby suppressing the inflammatory response that occurs during and following acute myocardial infarction. The formulation comprises an agent which is an intracellular inhibitor that is released within the targeted phagocytic cells, specifically macrophage/monocytes, and inhibits and/or destroys the macrophages and/or monocytes, thereby reducing the final zone of infarct and improving cardiac repair and myocardial remodeling. Since macrophages and monocytes possess the unique ability to phagocytose large bodies, the agent is formulated into a specific size such that it can enter cells primarily via phagocytosis.; Thus, the specifically sized formulation selectively targets monocytes/macrophages. The formulation may comprise an encapsulated agent, an embedded agent or a particulate agent, wherein the formulation is of a specific size, such that it can enter cells primarily via phagocytosis. The formulation is preferably in the size range of 0.03-1.0 microns.

10. 发明公开

EP1680130A2 DESENSITIZATION OF COMPLEMENT ACTIVATION USING MONOCYTE/MACROPHAGE INHIBITORY COMPOUNDS 审中-公开
标题翻译： WITH单核细胞/巨噬细胞炎症的化合物补体活化的脱敏
公开(公告)号：EP1680130A2
公开(公告)日：2006-07-19
申请号：EP04798779.7
申请日：2004-11-05
申请人： Biorest Ltd.
发明人： GOLOMB, Gershon , EPSTEIN, Hila
IPC分类号： A61K31/663
CPC分类号： A61K31/663 , A61K9/127
摘要： The present invention relates to methods and compositions designed for the prevention, reduction, treatment, or management of complement activation-related acute hypersensitivity also known as C-mediated pseudoallergy (CARPA) that results from the administration of a medicinal composition including, but not limited to, those compositions in liposomal, micellar, nanoparticle, emulsion, and colloidal formulations. The methods of the invention comprise the administration of an effective amount of one or more therapeutic agents containing one or more active compounds which specifically decreases or inhibits the activity of and/or eliminates or diminishes the amount of macrophages and/or monocytes. In preferred embodiments, the active compound is a bisphosphonate.

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