公开(公告)号：US06818669B2

公开(公告)日：2004-11-16

申请号：US09955485

申请日：2001-09-19

申请人： Michael A. Moskowitz ,  James K. Liao ,  Eyal S. Ron ,  Mary Nallin Omstead

发明人： Michael A. Moskowitz ,  James K. Liao ,  Eyal S. Ron ,  Mary Nallin Omstead

IPC分类号： A61K31351

CPC分类号： A61K31/7048 ,  A61K9/2018 ,  A61K9/2054 ,  A61K9/2846 ,  A61K31/198 ,  A61K31/505 ,  A61K31/519 ,  A61K31/525 ,  A61K31/7076 ,  A61K31/195 ,  A61K2300/00

摘要： A method and compositions are provided for increased cerebral bioavailability of blood-born compositions by administering the composition of interest while increasing brain NO levels. This increase in NO levels may be accomplished by stimulating increased production of NO by eNOS, especially by administering L-arginine, by administering agents that increase NO levels independent of ecNOS, or by any combination of these methods. As NO is increased, cerebral blood flow is consequently increased, and drugs in the blood stream are carried along with the increased flow into brain tissue. By increased flow, the site of action will be exposed to more drug molecules. By stimulating increased NO production, administration of drugs that are not easily introduced to the brain may be facilitated and/or the serum concentration necessary to achieve desired physiologic effects may be reduced.

摘要翻译： 提供了通过在增加脑NO水平的同时施用感兴趣的组合物来提高血液出生组合物的脑生物利用度的方法和组合物。 NO水平的这种增加可以通过刺激通过eNOS增加NO的产生，特别是通过施用L-精氨酸，通过施用增加NO水平而不依赖于ecNOS的药剂或通过这些方法的任何组合来实现。 随着NO增加，脑血流量增加，血液中的药物随着流入脑组织的增加而被携带。 通过增加流动，作用部位将暴露于更多的药物分子。 通过刺激增加的NO产生，可以促进不容易引入脑的药物的给药和/或可以降低达到所需生理学效果所需的血清浓度。

公开(公告)号：US6147109A

公开(公告)日：2000-11-14

申请号：US132848

申请日：1998-08-11

申请人： James K. Liao ,  Ulrich Laufs ,  Matthias Endres ,  Michael A. Moskowitz

发明人： James K. Liao ,  Ulrich Laufs ,  Matthias Endres ,  Michael A. Moskowitz

IPC分类号： A61K45/00 ,  A61K31/00 ,  A61K31/195 ,  A61K31/35 ,  A61K31/365 ,  A61P1/00 ,  A61P9/00 ,  A61P11/00 ,  A61P13/12 ,  A61P15/10 ,  A61P43/00

CPC分类号： A61K31/35

摘要： A new use for HMG-CoA reductase inhibitors is provided. In the instant invention, HMG-CoA reductase inhibitors are found to upregulate endothelial cell Nitric Oxide Synthase activity through a mechanism other than preventing the formation of oxidative-LDL. As a result, HMG-CoA reductase inhibitors are useful in treating or preventing conditions that result from the abnormally low expression and/or activity of endothelial cell Nitric Oxide Synthase. Such conditions include pulmonary hypertension, ischemic stroke, impotence, heart failure, hypoxia-induced conditions, insulin deficiency, progressive renal disease, gastric or esophageal motility syndrome, etc. Subjects thought to benefit mostly from such treatments include nonhyperlipidemics and nonhypercholesterolemics, but not necessarily exclude hyperlipidemics and hypercholesterolemics.

摘要翻译： 提供了HMG-CoA还原酶抑制剂的新用途。 在本发明中，发现HMG-CoA还原酶抑制剂通过除了防止形成氧化型-LDL之外的机制来上调内皮细胞一氧化氮合酶活性。 结果，HMG-CoA还原酶抑制剂可用于治疗或预防由内皮细胞一氧化氮合酶异常低的表达和/或活性引起的病症。 这些病症包括肺动脉高压，缺血性卒中，阳ence，心力衰竭，缺氧诱导的病症，胰岛素缺乏，进行性肾病，胃食管运动综合征等。受试者主要受益于此类治疗，包括非高脂血症和非高胆固醇血症，但不一定 排除高脂血症和高胆固醇血症。

公开(公告)号：US06423751B1

公开(公告)日：2002-07-23

申请号：US09115387

申请日：1998-07-14

申请人： James K. Liao

发明人： James K. Liao

IPC分类号： A61K3115

CPC分类号： A61K31/505 ,  A61K31/00 ,  A61K31/15 ,  A61K31/195 ,  A61K31/407 ,  A61K31/47 ,  A61K31/496 ,  A61K31/55 ,  A61K31/551 ,  A61K45/06 ,  A61K2300/00

摘要： A use for agents that disrupt actin cytoskeletal organization is provided. In the instant invention, agents that disrupt actin cytoskeletal organization are found to upregulate endothelial cell Nitric Oxide Synthase activity. As a result, agents that disrupt actin cytoskeletal organization are useful in treating or preventing conditions that result from the abnormally low expression and/or activity of endothelial cell Nitric Oxide Synthase. Such conditions include pulmonary hypertension, ischemic stroke, impotence, heart failure, hypoxia-induced conditions, insulin deficiency, progressive renal disease, gastric or esophageal motility syndrome, etc. Subjects thought to benefit mostly from such treatments include nonhyperlipidemics and nonhypercholesterolemics, but not necessarily exclude hyperlipidemics and hypercholesterolemics.

摘要翻译： 提供了一种用于破坏肌动蛋白细胞骨架组织的药剂。 在本发明中，发现破坏肌动蛋白细胞骨架组织的试剂上调内皮细胞一氧化氮合酶活性。 结果，破坏肌动蛋白细胞骨架组织的药物可用于治疗或预防由内皮细胞一氧化氮合酶异常低的表达和/或活性引起的病症。 这些病症包括肺动脉高压，缺血性卒中，阳ence，心力衰竭，缺氧诱导的病症，胰岛素缺乏，进行性肾病，胃食管运动综合征等。受试者主要受益于此类治疗，包括非高脂血症和非高胆固醇血症，但不一定 排除高脂血症和高胆固醇血症。

公开(公告)号：US06696480B2

公开(公告)日：2004-02-24

申请号：US10144669

申请日：2002-05-13

申请人： James K. Liao

发明人： James K. Liao

IPC分类号： A61K3115

CPC分类号： A61K31/505 ,  A61K31/00 ,  A61K31/15 ,  A61K31/195 ,  A61K31/407 ,  A61K31/47 ,  A61K31/496 ,  A61K31/55 ,  A61K31/551 ,  A61K45/06 ,  A61K2300/00

摘要： A use for agents that disrupt actin cytoskeletal organization is provided. In the instant invention, agents that disrupt actin cytoskeletal organization are found to upregulate endothelial cell Nitric Oxide Synthase activity. As a result, agents that disrupt actin cytoskeletal organization are useful in treating or preventing conditions that result from the abnormally low expression and/or activity of endothelial cell Nitric Oxide Synthase. Such conditions include hypoxia-induced conditions. Subjects thought to benefit mostly from such treatments include nonhyperlipidemics and nonhypercholesterolemics, but not necessarily exclude hyperlipidemics and hypercholesterolemics.

摘要翻译： 提供了一种用于破坏肌动蛋白细胞骨架组织的药剂。 在本发明中，发现破坏肌动蛋白细胞骨架组织的试剂上调内皮细胞一氧化氮合酶活性。 结果，破坏肌动蛋白细胞骨架组织的药物可用于治疗或预防由内皮细胞一氧化氮合酶异常低的表达和/或活性引起的病症。 这些病症包括缺氧诱导的病症。 认为主要受益于这些治疗的受试者包括非高脂血症和非高胆固醇血症，但不一定排除高脂血症和高胆固醇血症。

公开(公告)号：US06916843B1

公开(公告)日：2005-07-12

申请号：US09634369

申请日：2000-08-09

申请人： James K. Liao ,  Darryl Zeldin

发明人： James K. Liao ,  Darryl Zeldin

IPC分类号： A61K31/16 ,  A61K31/17 ,  A61K31/202 ,  A61K31/325 ,  A61K31/557 ,  A61K31/558 ,  A61K38/44 ,  A61K45/06 ,  A61K48/00 ,  C12Q1/26 ,  A61K31/335

CPC分类号： A61K31/559 ,  A61K31/16 ,  A61K31/17 ,  A61K31/202 ,  A61K31/325 ,  A61K31/557 ,  A61K31/558 ,  A61K38/44 ,  A61K45/06 ,  A61K48/00 ,  C12Q1/26 ,  C12Y114/14001 ,  G01N2500/04 ,  A61K2300/00

摘要： Epoxyeicosatrienoic acids (EETs) are products of cytocrome P450 epoxygenases that have vasodilatory properties similar to endotheilum-derived hyperpolarizing factor (EDHF). The cytochrome P450 isoform CYP2J2 was cloned and identified as a source of EETs in human endothelial cells. Physiological concentrations of EETs or overexpression of CYP2J2 decreased cytolcine-induced endothelial cell adhesion molecule expression and prevented subsequent leukocyte adhesion to the vascular wall by a mechanism involving inhibition of transcription factor NF-κB and IκB kinase (IKK). The inhibitory effects of EETs were independent of their membrane hyporpolarizing effects suggesting that these molecules play an important non-vasodilatory role in vascular inflammation.

摘要翻译： 环氧二十碳三烯酸（EETs）是具有类似于内皮衍生的超极化因子（EDHF）的血管扩张性质的细胞色素P450环氧化酶的产物。 克隆细胞色素P450同种型CYP2J2，并将其鉴定为人内皮细胞中EET的来源。 EETs的生理浓度或CYP2J2的过表达降低细胞因子诱导的内皮细胞粘附分子表达，并通过涉及抑制转录因子NF-κB和IkappaB激酶（IKK）的机制阻止随后的白细胞与血管壁的粘附。 EETs的抑制作用与其膜下极化作用无关，表明这些分子在血管炎症中发挥重要的非血管扩张作用。

公开(公告)号：US06566081B1

公开(公告)日：2003-05-20

申请号：US09680695

申请日：2000-10-06

申请人： James K. Liao ,  William Chin

发明人： James K. Liao ,  William Chin

IPC分类号： G01N3353

CPC分类号： G01N33/743 ,  A61K31/565 ,  A61K31/567 ,  A61K45/06 ,  C12Q1/485 ,  G01N2500/02 ,  G01N2500/04 ,  G01N2500/10 ,  A61K2300/00

摘要： This invention provides new methods and compounds for controlling the intracellular and physiological effects of steroid hormones, including but not limited to estrogen, through modulation of the interaction of such hormone receptors with phosphatidylinositol-3 kinase. Compounds and methods for controlling the activation of endotbelial nitric oxide synthase are also disclosed.

摘要翻译： 本发明提供了通过调节这种激素受体与磷脂酰肌醇-3激酶的相互作用来控制类固醇激素（包括但不限于雌激素）的细胞内和生理作用的新方法和化合物。 还公开了用于控制内皮一氧化氮合酶活化的化合物和方法。

公开(公告)号：US06180597B2

公开(公告)日：2001-01-30

申请号：US09132849

申请日：1998-08-11

申请人： James K. Liao

发明人： James K. Liao

IPC分类号： A61K3802

CPC分类号： A61K31/6615 ,  A61K31/00 ,  A61K31/366 ,  A61K38/46 ,  A61K45/06 ,  C12Y306/05002 ,  A61K2300/00

摘要： A use for rho GTPase function inhibitors is provided. In the instant invention, rho GTPase function inhibitors are found to upregulate endothelial cell Nitric Oxide Synthase activity. As a result, rho GTPase function inhibitors are useful in treating or preventing conditions that result from the abnormally low expression and/or activity of endothelial cell Nitric Oxide Synthase. Such conditions include pulmonary hypertension, ischemic stroke, impotence, heart failure, hypoxia-induced conditions, insulin deficiency, progressive renal disease, gastric or esophageal motility syndrome, etc. Subjects thought to benefit mostly from such treatments include nonhyperlipidemics and nonhypercholesterolemics, but do not necessarily exclude hyperlipidemics and hypercholesterolemics.

摘要翻译： 提供了一种用于rho GTP酶功能抑制剂的用途。 在本发明中，发现rho GTP酶功能抑制剂上调内皮细胞一氧化氮合酶活性。 结果，rho GTP酶功能抑制剂可用于治疗或预防由内皮细胞一氧化氮合酶异常低的表达和/或活性引起的病症。 这些病症包括肺动脉高压，缺血性卒中，阳ence，心力衰竭，缺氧诱导的病症，胰岛素缺乏症，进行性肾病，胃食管运动综合征等。受试者主要受益于此类治疗，包括非高脂血症和非高胆固醇血症，但不 必然排除高脂血症和高胆固醇血症。