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1. 发明授权

US08048880B2 Treatment of cardiovascular disease and dyslipidemia using secretory phospholipase A2 (SPLA2) inhibitors and SPLA2 inhibitor combination therapies 失效
标题翻译：使用分泌型磷脂酶A2（SPLA2）抑制剂和SPLA2抑制剂联合疗法治疗心血管疾病和血脂异常
公开(公告)号：US08048880B2
公开(公告)日：2011-11-01
申请号：US12114710
申请日：2008-05-02
申请人： Joaquim Trias , Colin Hislop , Paul Truex , Bernadine Fraser , Debra Odink , Scott Chadwick , Kenneth Gould , Marian Mosior , Patrick Eacho
发明人： Joaquim Trias , Colin Hislop , Paul Truex , Bernadine Fraser , Debra Odink , Scott Chadwick , Kenneth Gould , Marian Mosior , Patrick Eacho
IPC分类号： A61K31/535 , A61K31/397 , A61K31/44 , A61K31/40
CPC分类号： A61K31/397 , A61K31/404 , A61K31/4418 , A61K31/4422 , A61K31/505
摘要： Administration of sPLA2 inhibitors has been found to decrease cholesterol levels, atherosclerotic plaque formation and aortic aneurysm in mice, and to decrease cholesterol and triglyceride levels in humans. Interestingly, administration of sPLA2 inhibitors was found to decrease cholesterol levels even when the inhibitors were administered only once per day. Therefore, provided herein are methods of treating dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome, by administering one or more sPLA2 inhibitors. Significantly, administration of sPLA2 inhibitors and various compounds used in the treatment of CVD, such as for example statins, resulted in greater decreases in LDL and LDL particle levels in a synergistic manner. In addition, administration of sPLA2 inhibitors and statins resulted in a synergistic decrease in plaque content. Therefore, also provided herein are compositions comprising one or more sPLA2 inhibitors and one or more compounds used in the treatment of CVD, such as for example statins, and methods of using these compositions to treat dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome.
摘要翻译：已经发现sPLA2抑制剂的给药降低胆固醇水平，小鼠动脉粥样硬化斑块形成和主动脉瘤，并降低人体胆固醇和甘油三酯水平。有趣的是，即使抑制剂每天只给予一次，也发现施用sPLA2抑制剂降低胆固醇水平。因此，本文提供了通过施用一种或多种sPLA2抑制剂来治疗血脂异常，CVD和与CVD有关的病症如动脉粥样硬化和代谢综合征的方法。显着地，施用sPLA2抑制剂和用于治疗CVD的各种化合物，例如他汀类药物，以协同方式导致LDL和LDL颗粒水平的更大降低。此外，sPLA2抑制剂和他汀类药物的给药导致斑块含量的协同减少。因此，本文还提供了包含一种或多种sPLA2抑制剂和用于治疗CVD的一种或多种化合物的组合物，例如他汀类药物，以及使用这些组合物治疗血脂异常，CVD和与CVD相关的病症的方法，例如动脉粥样硬化和代谢综合征。

2. 发明申请

US20090131396A1 TREATMENT OF CARDIOVASCULAR DISEASE AND DYSLIPIDEMIA USING SECRETORY PHOSPHOLIPASE A2 (SPLA2) INHIBITORS AND SPLA2 INHIBITOR COMBINATION THERAPIES 失效
标题翻译：使用秘密磷脂酶A2（SPLA2）抑制剂和SPLA2抑制剂联合治疗治疗心血管疾病和血小板衍生症
公开(公告)号：US20090131396A1
公开(公告)日：2009-05-21
申请号：US12114710
申请日：2008-05-02
申请人： Joaquim Trias , Colin Hislop , Paul Truex , Bernadine Fraser , Debra Odink , Scott Chadwick , Kenneth Gould , Marian Mosior , Patrick Eacho
发明人： Joaquim Trias , Colin Hislop , Paul Truex , Bernadine Fraser , Debra Odink , Scott Chadwick , Kenneth Gould , Marian Mosior , Patrick Eacho
IPC分类号： A61K31/404 , A61P9/00 , A61K31/4418 , A61K31/505 , A61K31/4422 , A61K31/397
CPC分类号： A61K31/397 , A61K31/404 , A61K31/4418 , A61K31/4422 , A61K31/505
摘要： Administration of sPLA2 inhibitors has been found to decrease cholesterol levels, atherosclerotic plaque formation and aortic aneurysm in mice, and to decrease cholesterol and triglyceride levels in humans. Interestingly, administration of sPLA2 inhibitors was found to decrease cholesterol levels even when the inhibitors were administered only once per day. Therefore, provided herein are methods of treating dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome, by administering one or more sPLA2 inhibitors. Significantly, administration of sPLA2 inhibitors and various compounds used in the treatment of CVD, such as for example statins, resulted in greater decreases in LDL and LDL particle levels in a synergistic manner. In addition, administration of sPLA2 inhibitors and statins resulted in a synergistic decrease in plaque content. Therefore, also provided herein are compositions comprising one or more sPLA2 inhibitors and one or more compounds used in the treatment of CVD, such as for example statins, and methods of using these compositions to treat dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome.
摘要翻译：已经发现sPLA2抑制剂的给药降低胆固醇水平，小鼠动脉粥样硬化斑块形成和主动脉瘤，并降低人体胆固醇和甘油三酯水平。有趣的是，即使抑制剂每天只给予一次，也发现施用sPLA2抑制剂降低胆固醇水平。因此，本文提供了通过施用一种或多种sPLA2抑制剂来治疗血脂异常，CVD和与CVD相关的病症如动脉粥样硬化和代谢综合征的方法。显着地，施用sPLA2抑制剂和用于治疗CVD的各种化合物，例如他汀类药物，以协同方式导致LDL和LDL颗粒水平的更大降低。此外，sPLA2抑制剂和他汀类药物的给药导致斑块含量的协同减少。因此，本文还提供了包含一种或多种sPLA2抑制剂和用于治疗CVD的一种或多种化合物的组合物，例如他汀类药物，以及使用这些组合物治疗血脂异常，CVD和与CVD相关的病症的方法，例如动脉粥样硬化和代谢综合征。

3. 发明申请

US20110207710A1 TREATMENT OF CARDIOVASCULAR DISEASE AND DYSLIPIDEMIA USING SECRETORY PHOSPHOLIPASE A2 (SPLA2) INHIBITORS AND SPLA2 INHIBITOR COMBINATION THERAPIES 审中-公开
标题翻译：使用秘密磷脂酶A2（SPLA2）抑制剂和SPLA2抑制剂联合治疗治疗心血管疾病和血小板衍生症
公开(公告)号：US20110207710A1
公开(公告)日：2011-08-25
申请号：US13050898
申请日：2011-03-17
申请人： Joaquim TRIAS , Colin Hislop , Paul Truex , Bernadine Fraser , Debra Odink , Scott Chadwick
发明人： Joaquim TRIAS , Colin Hislop , Paul Truex , Bernadine Fraser , Debra Odink , Scott Chadwick
IPC分类号： A61K31/404 , A61P9/00 , A61P9/10 , A61P7/02 , A61P3/10 , A61K31/505 , A61K31/4418 , A61K31/403
CPC分类号： A61K31/397 , A61K31/404 , A61K31/4418 , A61K31/4422 , A61K31/505
摘要： Administration of sPLA2 inhibitors has been found to decrease cholesterol levels, atherosclerotic plaque formation and aortic aneurysm in mice, and to decrease cholesterol and triglyceride levels in humans. Interestingly, administration of sPLA2 inhibitors was found to decrease cholesterol levels even when the inhibitors were administered only once per day. Therefore, provided herein are methods of treating dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome, by administering one or more sPLA2 inhibitors. Significantly, administration of sPLA2 inhibitors and various compounds used in the treatment of CVD, such as for example statins, resulted in greater decreases in LDL and LDL particle levels in a synergistic manner. In addition, administration of sPLA2 inhibitors and statins resulted in a synergistic decrease in plaque content. Therefore, also provided herein are compositions comprising one or more sPLA2 inhibitors and one or more compounds used in the treatment of CVD, such as for example statins, and methods of using these compositions to treat dyslipidemia, CVD, and conditions associated with CVD such as atherosclerosis and metabolic syndrome.
摘要翻译：已经发现sPLA2抑制剂的给药降低胆固醇水平，小鼠动脉粥样硬化斑块形成和主动脉瘤，并降低人体胆固醇和甘油三酯水平。有趣的是，即使抑制剂每天只给予一次，也发现施用sPLA2抑制剂降低胆固醇水平。因此，本文提供了通过施用一种或多种sPLA2抑制剂来治疗血脂异常，CVD和与CVD有关的病症如动脉粥样硬化和代谢综合征的方法。显着地，施用sPLA2抑制剂和用于治疗CVD的各种化合物，例如他汀类药物，以协同方式导致LDL和LDL颗粒水平的更大降低。此外，sPLA2抑制剂和他汀类药物的给药导致斑块含量的协同减少。因此，本文还提供了包含一种或多种sPLA2抑制剂和用于治疗CVD的一种或多种化合物的组合物，例如他汀类药物，以及使用这些组合物治疗血脂异常，CVD和与CVD相关的病症的方法，例如动脉粥样硬化和代谢综合征。

4. 发明申请

US20110301202A1 SPLA2 INHIBITOR CONJUGATE COMPOUNDS AND METHODS OF USE 审中-公开
标题翻译： SPLA2抑制剂联合化合物及其使用方法
公开(公告)号：US20110301202A1
公开(公告)日：2011-12-08
申请号：US13152689
申请日：2011-06-03
申请人： Colin Hislop , Joaquim Trias , Debra Odink , Bernadine Fraser , Scott Chadwick
发明人： Colin Hislop , Joaquim Trias , Debra Odink , Bernadine Fraser , Scott Chadwick
IPC分类号： A61K31/4439 , A61P3/06 , C07D401/12
CPC分类号： A61K31/4439
摘要： The present application provides a novel set of compounds comprising a sPLA2 inhibitor conjugated to a niacin drug, as well as kits containing these compounds and methods of using the compounds to alter lipid levels and treat various cardiovascular diseases.
摘要翻译：本申请提供了一组新的化合物，其包含与烟酸药物缀合的sPLA2抑制剂，以及含有这些化合物的试剂盒，以及使用该化合物改变脂质水平和治疗各种心血管疾病的方法。

5. 发明申请

US20110269786A1 TREATMENT OF MAJOR ADVERSE CARDIAC EVENTS AND ACUTE CORONARY SYNDROME IN DIABETIC PATIENTS USING SECRETORY PHOSPHOLIPASE A2 (SPLA2) INHIBITOR OR SPLA2 INHIBITOR COMBINATION THERAPIES 审中-公开
标题翻译：使用秘密磷脂酶A2（SPLA2）抑制剂或SPLA2抑制剂组合治疗治疗糖尿病患者主要不良心脏事件和急性冠状综合征
公开(公告)号：US20110269786A1
公开(公告)日：2011-11-03
申请号：US13098261
申请日：2011-04-29
申请人： Colin Hislop , Joaquim Trias , Debra Odink , Paul Truex
发明人： Colin Hislop , Joaquim Trias , Debra Odink , Paul Truex
IPC分类号： A61K31/435 , A61K31/47 , A61P9/10 , A61K31/404
CPC分类号： A61K31/404 , A61K31/435 , A61K31/47 , A61K45/06 , A61K2300/00
摘要： Administration of sPLA2 inhibitors in combination with statins has been found to reduce the occurrence of major adverse cardiac events (MACEs), specifically unstable angina (UA) requiring urgent hospitalization, in diabetic subjects who have recently experienced an index ACS event to a significantly greater degree than statins alone. These results were unexpected given previous results showing that statins alone are insufficient to satisfactorily reduce MACEs and inflammation in this high-risk population, combined with the high levels of baseline inflammation associated with diabetes. Therefore, provided herein are methods of treating MACEs, including UA requiring urgent hospitalization, in a diabetic subject who has previously experienced an ACS event by administering one or more sPLA2 inhibitors alone or in combination with one or more statins.
摘要翻译：已经发现sPLA2抑制剂联合他汀类药物的治疗减少了最近经历了ACS事件发生率显着更高的糖尿病患者的主要不良心脏事件（MACE），特别是不稳定心绞痛（UA）需要紧急住院的发生比他汀类药物单独。以前的结果显示，仅仅他汀类药物不足以令人满意地减少这种高危人群的MACE和炎症，以及与糖尿病相关的高水平基线炎症，这些结果是出人意料的。因此，本文提供了通过单独施用一种或多种sPLA2抑制剂或与一种或多种他汀类药物组合施用的先前已经经历ACS事件的糖尿病受试者来治疗MACE（包括需要紧急住院的UA）的方法。

6. 发明申请

US20100160361A1 TREATMENT OF MAJOR ADVERSE CARDIAC EVENTS AND ACUTE CORONARY SYNDROME USING SECRETORY PHOSPHOLIPASE A2 (SPLA2) INHIBITOR OR SPLA2 INHIBITOR COMBINATION THERAPIES 审中-公开
标题翻译：使用秘密磷脂酶A2（SPLA2）抑制剂或SPLA2抑制剂组合治疗主要不良心脏事件和急性冠脉综合征的治疗
公开(公告)号：US20100160361A1
公开(公告)日：2010-06-24
申请号：US12642692
申请日：2009-12-18
申请人： Colin Hislop , Joaquim Trias , Debra Odink , Paul Truex
发明人： Colin Hislop , Joaquim Trias , Debra Odink , Paul Truex
IPC分类号： A61K31/404 , A61K31/505 , A61K31/435 , A61K31/47 , A61P9/10 , A61P9/00
CPC分类号： A61K45/06 , A61K31/404 , A61K31/435 , A61K31/47 , A61K31/505 , A61K2300/00
摘要： Administration of sPLA2 inhibitors in combination with statins has been found to reduce major adverse cardiac events (MACEs), inflammatory biomarker levels, and LDL-C levels in subjects who have recently experienced an index ACS event to a significantly greater degree than statins alone. These results were unexpected given previous results showing that statins alone are insufficient to satisfactorily reduce MACEs and inflammation in this high-risk population. Therefore, provided herein are methods of treating MACEs, treating ACS, inhibiting inflammation, and lowering cholesterol levels in a subject who has previously experienced an ACS event by administering one or more sPLA2 inhibitors alone or in combination with one or more statins.
摘要翻译：已经发现sPLA2抑制剂联合他汀类药物的治疗可以减少主要的不良心脏事件（MACE），炎性生物标志物水平和LDL-C水平，这些受试者最近经历了ACS事件的发生程度明显高于他汀类药物。以前的结果显示，仅仅他汀类药物不足以令人满意地减少这种高危人群的MACE和炎症，这些结果是出人意料的。因此，本文提供了通过单独或与一种或多种他汀类联合给药一种或多种sPLA2抑制剂来治疗MACE，治疗ACS，抑制炎症并降低先前已经经历ACS事件的受试者的胆固醇水平的方法。

7. 发明申请

US20090062369A1 USE OF SECRETORY PHOSPHOLIPASE A2 (SPLA2) INHIBITORS TO DECREASE SPLA2 LEVELS 审中-公开
标题翻译：使用秘密磷脂酶A2（SPLA2）抑制剂降低SPLA2水平
公开(公告)号：US20090062369A1
公开(公告)日：2009-03-05
申请号：US11849243
申请日：2007-08-31
申请人： Joaquim Trias , Colin Hislop
发明人： Joaquim Trias , Colin Hislop
IPC分类号： A61K31/404 , A61P9/00 , A61P9/04 , A61P9/10 , G01N33/53
CPC分类号： G01N33/573 , A61K31/404 , G01N2333/916
摘要： Administration of sPLA2 inhibitors has been found to decrease sPLA2 levels in human serum. Provided herein are methods of decreasing serum sPLA2 levels in a subject in need thereof, as well as methods for accurately measuring sPLA2 levels in a serum sample.
摘要翻译：已经发现sPLA2抑制剂的给药降低人血清中的sPLA2水平。本文提供了降低有需要的受试者血清sPLA2水平的方法，以及精确测量血清样品中sPLA2水平的方法。

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