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公开(公告)号：US08710092B2
公开(公告)日：2014-04-29
申请号：US12978314
申请日：2010-12-23
IPC分类号： A61K31/40
CPC分类号： C07D519/02 , C07D457/04
摘要： Provided herein are substituted indolo[4,3-fg]quinolines of Formula (I) and (II) where R1-R6 and R13 are as defined in the specification and pharmaceutical compositions thereof which are useful in treating, preventing, or ameliorating a variety of medical disorders such as, for example, migraine. In other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and or 5-HT1B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of regulating serotonin transport using the compounds and compositions disclosed herein.
摘要翻译： 本文提供了式（I）和（II）的取代的吲哚并[4,3-f]喹啉，其中R 1 -R 6和R 13如说明书及其药物组合物中所定义，其可用于治疗，预防或改善品种 的医学病症，例如偏头痛。 在其它实施方案中，本文提供了使用本文公开的化合物和组合物来激发受体例如5-HT1D和/或5-HT1B受体的方法。 在其它实施方案中，本文提供了使用本文公开的化合物和组合物拮抗或抑制受体例如5-HT 2B受体的活性的方法。 在其它实施方案中，本文提供了使用本文公开的化合物和组合物调节5-羟色胺转运的方法。
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公开(公告)号：US20110152280A1
公开(公告)日：2011-06-23
申请号：US12978314
申请日：2010-12-23
IPC分类号： A61K31/4985 , C07D519/02 , A61P25/06 , A61P25/16 , A61P25/24 , A61P25/00 , A61P1/08 , A61P3/00
CPC分类号： C07D519/02 , C07D457/04
摘要： Provided herein are novel ergoline derivatives and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and or 5-HT1B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of regulating serotonin transport using the compounds and compositions disclosed herein.
摘要翻译： 本文提供了新的麦角灵衍生物及其药物组合物。 在其它实施方案中，本文提供的是使用本文公开的化合物和组合物治疗，预防或改善各种医学病症例如偏头痛的方法。 在其它实施方案中，本文提供了使用本文公开的化合物和组合物来激发受体例如5-HT1D和/或5-HT1B受体的方法。 在其它实施方案中，本文提供了使用本文公开的化合物和组合物拮抗或抑制受体例如5-HT 2B受体的活性的方法。 在其它实施方案中，本文提供了使用本文公开的化合物和组合物调节5-羟色胺转运的方法。
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3.发明申请Method Of Therapeutic Administration of DHE To Enable Rapid Relief Of Migraine While Minimizing Side Effect Profile 审中-公开DHE治疗管理方法可以使偏头痛快速缓解，同时尽量减少副作用公开(公告)号：US20120245179A1
公开(公告)日：2012-09-27
申请号：US13406391
申请日：2012-02-27
CPC分类号： A61K31/4985 , A61K9/0073 , A61K9/0075 , A61K31/10 , A61K31/48
摘要： Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.
摘要翻译： 公开了含有二氢麦角胺（DHE）的药物组合物和其中向患者施用DHE以治疗偏头痛而没有副作用或副作用的方法。 公开了用DHE快速治疗偏头痛的方法，其包括：抑制峰值血浆浓度（C max）并稍微延迟峰值，以避免激活多巴胺能和肾上腺素能受体，同时实现足够的活性结合5-羟色胺受体以缓解偏头痛 在允许快速解决偏头痛症状的时间范围内的症状。 公开了适用于该方法的吸入器。 公开了实施发明方法的试剂盒。
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公开(公告)号：US08148377B2
公开(公告)日：2012-04-03
申请号：US12069667
申请日：2008-02-11
IPC分类号： A61K31/48
CPC分类号： A61K31/4985 , A61K9/0073 , A61K9/0075 , A61K31/10 , A61K31/48
摘要： Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.
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5.发明申请Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile 有权DHE的治疗性给药方法，能够快速缓解偏头痛，同时尽量减少副作用公开(公告)号：US20080287451A1
公开(公告)日：2008-11-20
申请号：US12069667
申请日：2008-02-11
IPC分类号： A61K31/4985 , A61P25/06
CPC分类号： A61K31/4985 , A61K9/0073 , A61K9/0075 , A61K31/10 , A61K31/48
摘要： Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.
摘要翻译： 公开了含有二氢麦角胺（DHE）的药物组合物和其中向患者施用DHE以治疗偏头痛而没有副作用或副作用的方法。 公开了用DHE快速治疗偏头痛的方法，其包括：抑制峰值血浆浓度（C max max），并稍微延迟峰值，以避免活化多巴胺能和肾上腺素能受体，同时实现足够的活性结合 5-羟色胺受体在允许快速解决偏头痛症状的时间范围内缓解偏头痛症状。 公开了适用于该方法的吸入器。 公开了实施发明方法的试剂盒。
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公开(公告)号：US08604035B2
公开(公告)日：2013-12-10
申请号：US13531371
申请日：2012-06-22
申请人： Robert O. Cook , Jian Zhang , Thomas A. Armer
发明人： Robert O. Cook , Jian Zhang , Thomas A. Armer
IPC分类号： A01N43/58 , A01N43/60 , A61K31/50 , A61K31/495
CPC分类号： C07D519/02 , A61K9/0075 , A61K9/0078 , A61K31/495 , A61K31/4985 , C07D457/04 , C07D498/04 , C07D498/14 , C07D519/00
摘要： Provided herein are novel fluoroergoline derivatives and compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, migraine using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of agonizing receptors such as, for example, the 5-HT1D and/or the 5-HT1B receptor, without agonizing the 5-HT2B receptor using the compounds and compositions disclosed herein. In still other embodiments, provided herein are methods of antagonizing or inhibiting activity at receptors such as, for example, the adrenergic alpha2A and/or the alpha2B receptors using the compounds and compositions disclosed herein.
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7.发明申请MULTIPLE ACTIVE PHARMACEUTICAL INGREDIENTS COMBINED IN DISCRETE INHALATION PARTICLES AND FORMULATIONS THEREOF 审中-公开多种活性药物成分组合在分离的吸入颗粒中及其配方公开(公告)号：US20100183725A1
公开(公告)日：2010-07-22
申请号：US11988913
申请日：2006-07-17
申请人： Nahed M. Mohsen , Thomas A. Armer , Robert O. Cook
发明人： Nahed M. Mohsen , Thomas A. Armer , Robert O. Cook
CPC分类号： A61K9/0073 , A61K31/167 , A61K31/58 , A61K45/06 , A61K2300/00
摘要： The present disclosure describe inhalation particles where each discrete unagglomerated inhalation particle comprising 2 or more active pharmaceutical ingredients. In one embodiment, the inhalation particles comprise a first and a second API where the second API covers, at least partially, and protects the first API from degradation or instability. Inhalation particles comprising a first and a second API as described herein have many advantages over present means of delivering two or more APIs. Formulations comprising such inhalation particles are also described.
摘要翻译： 本公开描述了吸入颗粒，其中每个离散的未聚集的吸入颗粒包含2种或更多种活性药物成分。 在一个实施方案中，吸入颗粒包含第一和第二API，其中第二API至少部分地覆盖并保护第一API免于退化或不稳定。 包含如本文所述的第一和第二API的吸入颗粒与递送两个或更多个API的现有手段相比具有许多优点。 还描述了包含这种吸入颗粒的制剂。
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公开(公告)号：US20090081297A1
公开(公告)日：2009-03-26
申请号：US11412523
申请日：2006-04-27
申请人： Robert O. Cook , Thomas A. Armer
发明人： Robert O. Cook , Thomas A. Armer
摘要： The present disclosure describes aerosol formulations that are particularly effective for pulmonary aerosol delivery. The aerosol formulations comprise an aqueous dispersion of active agent particles, said aqueous dispersion having an excess of a surface tension reducing agent. As a result of the reduced surface tension of the aqueous dispersion, the resulting aerosol droplets formed have a particle size less in one embodiment of than 10 microns in size or in an alternate embodiment of less than 6 microns in size. The present disclosure also provides for a method for forming an aerosol from said aerosol formulation, a method of treating a mammal in need of said treatment using said aerosol formulation, and a method of diagnosing a mammal in need of such diagnosis using said aerosol formulation.
摘要翻译： 本公开描述了对肺部气雾剂递送特别有效的气雾剂制剂。 气溶胶制剂包含活性剂颗粒的水分散体，所述水分散体具有过量的表面张力降低剂。 由于水性分散体的表面张力降低，所形成的所得气溶胶微滴的尺寸在一个实施方案中的尺寸小于10微米，或在尺寸小于6微米的替代实施方案中具有较小的粒度。 本公开还提供了用于从所述气溶胶制剂形成气溶胶的方法，使用所述气溶胶制剂治疗需要所述治疗的哺乳动物的方法，以及使用所述气溶胶制剂诊断需要进行诊断的哺乳动物的方法。
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9.发明申请公开(公告)号：US20100081664A1
公开(公告)日：2010-04-01
申请号：US12548304
申请日：2009-08-26
IPC分类号： A61K31/4985 , A61P25/06 , A61M15/00
CPC分类号： A61K31/4985 , A61K9/0073 , A61K9/0075 , A61K31/10 , A61K31/48
摘要： Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.
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10.发明申请METHOD OF THERAPEUTIC ADMINISTRATION OF DHE TO ENABLE RAPID RELIEF OF MIGRAINE WHILE MINIMIZING SIDE EFFECT PROFILE 有权DHE治疗方法可以使最小化侧面影响特征的影像快速缓解公开(公告)号：US20100081663A1
公开(公告)日：2010-04-01
申请号：US12548292
申请日：2009-08-26
IPC分类号： A61K31/4985 , A61P25/06 , A61M15/00
CPC分类号： A61K31/4985 , A61K9/0073 , A61K9/0075 , A61K31/10 , A61K31/48
摘要： Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (Cmax) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.
摘要翻译： 公开了含有二氢麦角胺（DHE）的药物组合物和其中向患者施用DHE以治疗偏头痛而没有副作用或副作用的方法。 公开了用DHE快速治疗偏头痛的方法，其包括：抑制峰值血浆浓度（C max）并稍微延迟峰值，以避免激活多巴胺能和肾上腺素能受体，同时实现足够的活性结合5-羟色胺受体以缓解偏头痛 在允许快速解决偏头痛症状的时间范围内的症状。 公开了适用于该方法的吸入器。 公开了实施发明方法的试剂盒。
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