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    • 9. 发明申请
    • TREATMENT OF CARDIOVASCULAR DISEASE AND DYSLIPIDEMIA USING SECRETORY PHOSPHOLIPASE A2 (SPLA2) INHIBITORS AND SPLA2 INHIBITOR COMBINATION THERAPIES
    • 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
    • US20110207710A1
    • 2011-08-25
    • US13050898
    • 2011-03-17
    • Joaquim TRIASColin HislopPaul TruexBernadine FraserDebra OdinkScott Chadwick
    • Joaquim TRIASColin HislopPaul TruexBernadine FraserDebra OdinkScott Chadwick
    • A61K31/404A61P9/00A61P9/10A61P7/02A61P3/10A61K31/505A61K31/4418A61K31/403
    • A61K31/397A61K31/404A61K31/4418A61K31/4422A61K31/505
    • 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.
    • 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。