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1. 发明授权

US5216025A Nitric oxide synthesis inhibitors for potentiating the action of pressor agents in certain hypotensive patients 失效
标题翻译：一氧化氮合成抑制剂用于增强某些低血压患者的加压剂的作用
公开(公告)号：US5216025A
公开(公告)日：1993-06-01
申请号：US723480
申请日：1991-07-01
申请人： Steven S. Gross , Robert G. Kilbourn , Roberto Levi
发明人： Steven S. Gross , Robert G. Kilbourn , Roberto Levi
IPC分类号： A61K31/13 , A61K31/195 , A61K31/198 , A61K31/223 , A61K38/04 , A61K38/19 , A61K38/20 , A61K38/21 , A61K45/06 , A61P9/02
CPC分类号： A61K38/085 , A61K31/195 , A61K31/198 , A61K31/223 , A61K45/06 , Y10S514/93
摘要： A method for treatment of an animal for systemic hypotension induced by internal nitric oxide production caused by endotoxin or cytokines. The method involves administering an .alpha..sub.1 adrenergic agonist and an amount of an inhibitor of nitric oxide formation from argiResearch relating to the development of this invention was supported by the United States Public Health Service grants which gives the United States government certain rights to use of the present invention.
摘要翻译：由内毒素或细胞因子引起的内部一氧化氮产生诱导的全身性低血压动物的治疗方法。该方法包括从精氨酸施用α1肾上腺素能激动剂和一定量的一氧化氮形成抑制剂以恢复对α1肾上腺素能激动剂的血管收缩敏感性。一氧化氮形成的优选抑制剂是在胍基氨基上具有至少一个氢原子的NG取代的精氨酸，其被另一个原子或分子物质替代，包括NG-氨基精氨酸，NG-硝基精氨酸和NG-烷基精氨酸如NG-甲基精氨酸， NG-乙精氨酸，NG-丙精氨酸和NG-精氨酸。精氨酸衍生物抑制剂优选为L构型，并且包括药学上可接受的加成盐。用生物反应调节剂如肿瘤坏死因子或白细胞介素-2进行化疗诱导的患者的系统性低血压的治疗可以同样完成。治疗由内毒素或其他细菌毒素（例如败血性休克）引起的全身性低血压的动物也可以通过用α1肾上腺素能激动剂和抑制剂如精氨酸衍生物进行治疗来实现，其恢复对α1肾上腺素能的血管收缩敏感性激动剂。

2. 发明授权

US5770623A Argine antagonists for inhibition of systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor 失效
标题翻译：用于抑制与一氧化氮产生或内皮衍生的松弛因子相关的全身性低血压的Argine拮抗剂
公开(公告)号：US5770623A
公开(公告)日：1998-06-23
申请号：US561717
申请日：1995-11-22
申请人： Robert G. Kilbourn , Steven S. Gross , Roberto Levi , Owen W. Griffith
发明人： Robert G. Kilbourn , Steven S. Gross , Roberto Levi , Owen W. Griffith
IPC分类号： A61K31/195 , A61K31/198 , A61K31/223 , A61K31/44
CPC分类号： A61K31/223 , A61K31/195 , A61K31/198 , A61K31/44 , Y10S514/93
摘要： A method for prophylaxis or treatment of an animal for systemic hypotension induced by internal nitrogen oxide production. The method involves administering a therapeutically effective amount of certain arginine derivatives to inhibit nitrogen oxide formation from arginine. Preferably N.sup.G -substituted arginine or an N.sup.G,N.sup.G -disubstituted arginine (having at least one hydrogen on a terminal guanidino amino group replaced by another atomic species) is administered to an animal possibly developing or already having such induced systemic hypotension. The arginine derivatives are preferably of the L configuration and include pharmaceutically acceptable addition salts. Prophylaxis or treatment of systemic hypotension in a patient which has been induced by chemotherapeutic treatment with biologic response modifiers such as tumor necrosis factor or interleukin-2 may be accomplished. Treatment of an animal for systemic hypotension induced by endotoxin, i.e., septic shock may also be accomplished by treatment with the arginine derivatives.
摘要翻译：一种用于预防或治疗由内部氮氧化物产生引起的全身性低血压的动物的方法。该方法包括施用治疗有效量的某些精氨酸衍生物以抑制由精氨酸形成的氮氧化物。优选将NG取代的精氨酸或NG，NG-二取代的精氨酸（在末端胍基氨基上具有至少一个氢被另一种原子物质取代）给予可能发展或已经具有这种诱发的全身性低血压的动物。精氨酸衍生物优选为L构型，并且包括药学上可接受的加成盐。可以通过生物反应调节剂如肿瘤坏死因子或白细胞介素-2进行化学治疗诱导的患者中预防或治疗全身性低血压。由内毒素引起的系统性低血压的治疗，即败血性休克也可以通过用精氨酸衍生物进行治疗来实现。

3. 发明授权

US5028627A Method of using arginine derivatives to inhibit systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor 失效
标题翻译：使用精氨酸衍生物抑制与一氧化氮产生或内皮衍生松弛因子相关的全身性低血压的方法
公开(公告)号：US5028627A
公开(公告)日：1991-07-02
申请号：US406909
申请日：1989-09-13
申请人： Robert G. Kilbourn , Steven Gross , Roberto Levi , Owen W. Griffith
发明人： Robert G. Kilbourn , Steven Gross , Roberto Levi , Owen W. Griffith
IPC分类号： A61K31/00 , A61K31/195 , A61K31/198 , A61K31/223 , A61K38/00 , A61K38/21 , A61K45/00 , A61P9/02 , A61P43/00
CPC分类号： A61K31/00 , A61K31/195 , A61K31/198 , A61K31/223 , Y10S514/93
摘要： A method for prophylaxis of treatment of an animal for systemic hypotension induced by internal nitrogen oxide production. The method involves administering a therapeutically effective amount of certain arginine derivatives to inhibit nitrogen oxide formation from arginine. Preferaby N.sup.G -substituted arginine or an N.sup.G,N.sup.G -disubstituted arginine (having at least one hydrogen on a terminal guanidino amino group replaced by another atomic species) is administered to an animal possibly developing or already having induced systemic hypotension. The arginine derivatives are preferably of the L configuration and include pharmaceutically acceptable addition salts. Prophylaxis or treatment or systemic hypotension in a patient which has been induced by chemotherapeutic treatment with biologic response modifiers such as tumor necrosis factor or interleukin-2 may be accomplished. Treatment of an animal for systemic hypotension induced by endotoxin, i.e., septic shock may also be accomplished by treatment with the arginine derivatives.
摘要翻译：一种用于预防由内部氮氧化物产生引起的全身性低血压的动物治疗的方法。该方法包括施用治疗有效量的某些精氨酸衍生物以抑制由精氨酸形成的氮氧化物。优选NG取代的精氨酸或NG，NG-二取代精氨酸（在由另一种原子物质取代的末端胍基氨基上具有至少一个氢）向可能发展或已经具有诱导的全身性低血压的动物施用。精氨酸衍生物优选为L构型，并且包括药学上可接受的加成盐。可以通过用生物反应调节剂如肿瘤坏死因子或白细胞介素-2进行化学治疗诱导的患者中的预防或治疗或全身性低血压。由内毒素引起的系统性低血压的治疗，即败血性休克也可以通过用精氨酸衍生物进行治疗来实现。

4. 发明授权

US5395612A Method for treating systemic hypotension caused by sepsis or cytokine using arginase in combination with an .alpha..sub.1 adrenergic agonist 失效
标题翻译：使用精氨酸酶与α1肾上腺素能激动剂组合治疗由败血症或细胞因子引起的全身性低血压的方法
公开(公告)号：US5395612A
公开(公告)日：1995-03-07
申请号：US814808
申请日：1991-12-31
申请人： Owen W. Griffith , Steven S. Gross , Roberto Levi
发明人： Owen W. Griffith , Steven S. Gross , Roberto Levi
IPC分类号： A61K38/50 , A61K38/46
CPC分类号： A61K38/50
摘要： Reducing plasma levels of endogenous arginine by parenteral administration of arginine depleting agent limits nitric oxide formation and results in blood pressure increase. Preferably arginase is administered intravenously to raise blood pressure. The arginine depleting agent can be administered in conjunction with arginine antagonists to potentiate the effect of these. The arginine depleting agent can be used concurrently with .alpha..sub.1 adrenergic agonists in treating systemic hypotension caused by induced production of nitric oxide, to restore vascular contractile sensitivity to the effect of the .alpha..sub.1 adrenergic agonists. Duration of action and avoidance of antigenicity may be obtained by use in conjunction with a carrier or modifier.
摘要翻译：通过肠外给药精氨酸消耗剂降低内源性精氨酸的血浆水平限制了一氧化氮的形成并导致血压升高。优选静脉内给予精氨酸酶以提高血压。精氨酸消耗剂可以与精氨酸拮抗剂一起施用以增强这些作用。精氨酸消耗剂可以与α1肾上腺素能激动剂同时使用，用于治疗由诱导的一氧化氮产生引起的全身性低血压，以恢复对α1肾上腺素能激动剂的作用的血管收缩敏感性。通过与载体或改性剂结合使用可以获得作用的持续时间和抗原性的避免。

5. 发明申请

US20090081274A1 MAST CELL-DERIVED RENIN 审中-公开
标题翻译： MAST细胞衍生的RENIN
公开(公告)号：US20090081274A1
公开(公告)日：2009-03-26
申请号：US12237176
申请日：2008-09-24
申请人： Randi B. Silver , Roberto Levi
发明人： Randi B. Silver , Roberto Levi
IPC分类号： A61F2/00 , A61K31/7088 , A61K38/08 , A61K9/12 , C07H21/02 , A61K38/10 , A61K31/40
CPC分类号： A61K45/06 , A61K31/00 , A61K31/401 , A61K38/08 , A61K38/10 , A61K2300/00
摘要： The invention relates to the discovery that renin is present in mast cells and can act in a localized manner to initiate and/or exacerbate a number of conditions. Thus, the invention provides methods for treating cardiac, vascular, lung, liver, cervical, intestinal, muscle, pancreatic, brain, kidney, skin and other conditions that involve inhibiting the synthesis and/or release of renin from mast cells and/or inhibiting the activity of renin after release from mast cells. The methods of the invention can also involve inhibiting elements of the local renin-angiotensin system (e.g. inhibiting ACE and angiotensin II receptors), thereby inhibiting angiotensin II produced locally from mast-cell-derived renin
摘要翻译：本发明涉及发现肾素存在于肥大细胞中并且可以以局部方式起作用和/或加剧许多病症。因此，本发明提供了治疗心脏，血管，肺，肝，宫颈，肠，肌肉，胰腺，脑，肾，皮肤和其它涉及抑制肾素从肥大细胞的合成和/或释放和/或抑制肾素从肥大细胞释放后的活性。本发明的方法还可以包括抑制局部肾素 - 血管紧张素系统的元件（例如抑制ACE和血管紧张素II受体），由此抑制由肥大细胞衍生的肾素局部产生的血管紧张素II

6. 发明授权

US06884809B2 Method and compositions for reducing cardiac dysfunctions with a selective histamine H3 receptor agonist 失效
标题翻译：用选择性组胺H3受体激动剂降低心脏功能障碍的方法和组合物
公开(公告)号：US06884809B2
公开(公告)日：2005-04-26
申请号：US10076204
申请日：2002-02-13
申请人： Roberto Levi , Randi B. Silver
发明人： Roberto Levi , Randi B. Silver
IPC分类号： A61K31/00 , A61K31/4164 , A61K31/417 , A61K31/4178 , A61K31/454 , A61K45/06 , A61P9/00 , A61P9/04 , A61P9/08 , A61P9/10 , A61K31/445 , A61K31/415
CPC分类号： A61K45/06 , A61K31/00 , A61K31/4164 , A61K31/417 , A61K31/4178 , A61K31/454
摘要： The invention provides a method for reducing cardiac dysfunctions in a human. The method comprises administration to the human of an effective amount of a selective histamine H3 Receptor agonist. In one embodiment, the method comprises limiting the accumulation of intracellular sodium (Nai) by inhibiting the Na+/H+ exchanger activity in the human having a cardiac dysfunction, or a predisposition to a cardiac dysfunction. In another embodiment the method comprises inhibiting the N-type Ca2+ channel to modulate the concentration of intracellular calcium. The invention also provides a pharmaceutical composition that includes a selective histamine H3 Receptor agonist with a pharmaceutical carrier.
摘要翻译：本发明提供一种减少人类心脏功能障碍的方法。该方法包括给予人有效量的选择性组胺H 3受体激动剂。在一个实施方案中，该方法包括通过抑制Na + / 具有心脏功能障碍的人，或心脏功能障碍的倾向。在另一个实施方案中，该方法包括抑制N型Ca 2+通道调节细胞内钙的浓度。本发明还提供了药物组合物，其包含选择性组胺H 3受体激动剂与药物载体。

7. 发明申请

US20050209141A1 Mast cell-derived renin 审中-公开
标题翻译：肥大细胞衍生的肾素
公开(公告)号：US20050209141A1
公开(公告)日：2005-09-22
申请号：US10964567
申请日：2004-10-13
申请人： Randi Silver , Roberto Levi
发明人： Randi Silver , Roberto Levi
IPC分类号： A61K31/00 , A61K31/401 , A61K38/08 , A61K38/10 , A61K38/17 , A61K45/06 , A61K48/00
CPC分类号： A61K45/06 , A61K31/00 , A61K31/401 , A61K38/08 , A61K38/10 , A61K2300/00
摘要： The invention relates to the discovery that renin is present in mast cells and can act in a localized manner to initiate and/or exacerbate a number of conditions. Thus, the invention provides methods for treating cardiac, vascular, lung, liver, cervical, intestinal, muscle, pancreatic, brain, kidney, skin and other conditions that involve inhibiting the synthesis and/or release of renin from mast cells and/or inhibiting the activity of renin after release from mast cells. The methods of the invention can also involve inhibiting elements of the local renin-angiotensin system (e.g. inhibiting ACE and angiotensin II receptors), thereby inhibiting angiotensin II produced locally from mast-cell-derived renin
摘要翻译：本发明涉及发现肾素存在于肥大细胞中并且可以以局部方式起作用和/或加剧许多病症。因此，本发明提供了治疗心脏，血管，肺，肝，宫颈，肠，肌肉，胰腺，脑，肾，皮肤和其它涉及抑制肾素从肥大细胞的合成和/或释放和/或抑制肾素从肥大细胞释放后的活性。本发明的方法还可以包括抑制局部肾素 - 血管紧张素系统的元件（例如抑制ACE和血管紧张素II受体），由此抑制由肥大细胞衍生的肾素局部产生的血管紧张素II

8. 发明申请

US20080032918A1 Mast cell-derived renin 审中-公开
标题翻译：肥大细胞衍生的肾素
公开(公告)号：US20080032918A1
公开(公告)日：2008-02-07
申请号：US11657343
申请日：2007-01-24
申请人： Randi Silver , Roberto Levi
发明人： Randi Silver , Roberto Levi
IPC分类号： A61K38/00 , A61K48/00 , A61P1/00
CPC分类号： A61K45/06 , A61K31/00 , A61K31/401 , A61K38/08 , A61K38/10 , A61K2300/00
摘要： The invention relates to the discovery that renin is present in mast cells and can act in a localized manner to initiate and/or exacerbate a number of conditions. Thus, the invention provides methods for treating cardiac, vascular, lung, liver, cervical, intestinal, muscle, pancreatic, brain, kidney, skin and other conditions that involve inhibiting the synthesis and/or release of renin from mast cells and/or inhibiting the activity of renin after release from mast cells. The methods of the invention can also involve inhibiting elements of the local renin-angiotensin system (e.g. inhibiting ACE and angiotensin II receptors), thereby inhibiting angiotensin II produced locally from mast-cell-derived renin.
摘要翻译：本发明涉及发现肾素存在于肥大细胞中并且可以以局部方式起作用和/或加剧许多病症。因此，本发明提供了治疗心脏，血管，肺，肝，宫颈，肠，肌肉，胰腺，脑，肾，皮肤和其它涉及抑制肾素从肥大细胞的合成和/或释放和/或抑制肾素从肥大细胞释放后的活性。本发明的方法还可以包括抑制局部肾素 - 血管紧张素系统的元件（例如抑制ACE和血管紧张素II受体），从而抑制由肥大细胞衍生的肾素局部产生的血管紧张素II。

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