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1. 发明申请

WO1993005780A1 AMINO ACIDS CONTAINING PARENTERAL FORMULATIONS FOR THE TREATMENT OF HYPOTENSION AND RELATED PATHOLOGIES 审中-公开
标题翻译：含有治疗高血压和相关病理学的参考配方的氨基酸
公开(公告)号：WO1993005780A1
公开(公告)日：1993-04-01
申请号：PCT/US1992008227
申请日：1992-09-26
申请人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , CORNELL RESEARCH FOUNDATION, INC.
发明人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , CORNELL RESEARCH FOUNDATION, INC. , KILBOURN, Robert, G. , GRIFFITH, Owen, W. , GROSS, Steven, S.
IPC分类号： A61K31/415
CPC分类号： A61K31/715 , A61K31/415 , A61K38/20 , A61K38/19 , A61K31/405 , A61K31/40 , A61K31/195 , A61K38/04 , A61K2300/00
摘要： An anti-hypotensive formulation comprising an essentially arginine-free or low arginine (less than about 0.1 %, most preferably, about 0.01 %) containing mixture of amino acids is provided. The formulations may further include ornithine, citrulline or both. Combination regimens of the described TPN solutions and an arginine analog, or the TPN formations with an anti-endotoxine antibody, an interleukin-1 receptor antagonist, or an anti-tumor necrosis antibody are also provided. Methods for prophylaxis and treatment of systemic hypotension in employing these combination regimens are also provided. A method for treating hypotension caused by nitric oxide synthesis, through administering a low or essentially arginine-free parenteral formulation is described. Methods for treating an animal in septic shock are also disclosed. Prophylaxis or treatment of systemic hypotension, particularly that hypotension incident to chemotherapeutic treatment with biologic response modifiers, such as tumor necrosis factor or interleukin-1 or -2, may be accomplished through the administration of the defined anti-hypotensive formulations or combination regimens with a TPN formulation until physiologically acceptable systolic blood pressure levels are achieved in the animal. Treatment of an animal for septic shock induced by endotoxin may also be accomplished by administering to the animal the arginine-free formulations described. Methods for providing nutritional support for an animal at risk of or in septic shock may also be provided through the administration of an arginine-free formulation or the combination regimens.
摘要翻译：提供包含基本上不含精氨酸或低精氨酸（小于约0.1％，最优选约0.01％）的包含氨基酸混合物的抗低血压制剂。制剂还可包括鸟氨酸，瓜氨酸或两者。还提供了所述TPN溶液和精氨酸类似物或具有抗内毒素抗体，白介素-1受体拮抗剂或抗肿瘤坏死抗体的TPN结构的组合方案。还提供了在使用这些联合方案时预防和治疗全身性低血压的方法。描述了通过施用低或基本上不含精氨酸的肠胃外制剂来治疗由一氧化氮合成引起的低血压的方法。还公开了用于治疗脓毒性休克的动物的方法。预防或治疗全身性低血压，特别是生物反应调节剂（如肿瘤坏死因子或白细胞介素-1或-2）对化疗治疗的低血压可以通过给予定义的抗低血压药物或组合方案与 TPN制剂在动物中达到生理上可接受的收缩压水平。内毒素引起的脓毒性休克动物的治疗也可以通过向动物施用所述的不含精氨酸的制剂来实现。还可以通过施用无精氨酸制剂或组合方案来提供危险的或在脓毒性休克中的动物的营养支持的方法。

2. 发明申请

WO1993000893A1 NITRIC OXIDE SYNTHESIS INHIBITORS FOR POTENTIATING THE ACTION OF PRESSOR AGENTS IN CERTAIN HYPOTENSIVE PATIENTS 审中-公开
标题翻译：氮氧化物合成抑制剂，用于潜伏在某些低温患者中的压疮药物
公开(公告)号：WO1993000893A1
公开(公告)日：1993-01-21
申请号：PCT/US1992005570
申请日：1992-07-01
申请人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , CORNELL RESEARCH FOUNDATION, INC.
发明人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , CORNELL RESEARCH FOUNDATION, INC. , GROSS, Steven, S. , KILBOURN, Robert, G. , LEVI, Roberto
IPC分类号： A61K31/195
CPC分类号： A61K38/085 , A61K31/195 , A61K31/198 , A61K31/223 , A61K45/06 , Y10S514/93 , A61K38/217 , A61K31/135 , A61K38/20 , A61K38/191 , A61K38/19 , A61K38/04 , A61K2300/00
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 1 adrenergic agonist and an amount of an inhibitor of nitric oxide formation from arginine restoring vascular contractile sensitivity to DOLLAR (a)1 adrenergic agonists. Preferable N -substituted arginine (having at least one hydrogen on a guanidino amino group replaced by another atomic or molecular species). The inhibitor is administered to an animal having such induced systemic hypotension. Arginine derivative inhibitors are preferably of the L configuration and include pharmaceutically acceptable addition salts. Treatment of systemic hypotension in a patient which has been induced by chemotherapy with biologic response modifiers such as tumor necrosis factor or interleukin-2 may be likewise accomplished. Treatment of an animal for systemic hypotension induced by endotoxin, or other bacterial toxins, e.g., septic shock, may also be accomplished by treatment with alpha 1 adrenergic agonists and an inhibitor such as an arginine derivative, restoring vascular contractile sensitivity to the alpha 1 adrenergic agonists.
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。该方法包括施用α1肾上腺素能激动剂和一定量的从精氨酸形成的一氧化氮抑制剂，使DOLLAR（a）1肾上腺素能激动剂恢复血管收缩敏感性。优选的N，N-取代精氨酸（胍基氨基上至少有一个氢原子被另一种原子或分子物质取代）。将抑制剂施用于具有这种诱发的全身性低血压的动物。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介素-2进行化疗诱导的患者的全身性低血压的治疗也可以同样完成。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。

3. 发明申请

WO1993016721A1 INHIBITION OF NITRIC OXIDE-MEDIATED HYPOTENSION AND SEPTIC SHOCK WITH IRON-CONTAINING HEMOPROTEIN 审中-公开
标题翻译：氮氧化物介导的羟基磷灰石抑制氧化还原和分离性休克
公开(公告)号：WO1993016721A1
公开(公告)日：1993-09-02
申请号：PCT/US1993001288
申请日：1993-02-16
申请人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , DUKE UNIVERSITY , APEX BIOSCIENCE, INC.
发明人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , DUKE UNIVERSITY , APEX BIOSCIENCE, INC. , KILBOURN, Robert, G. , DE ANGELO, Joseph , BONAVENTURA, Joseph
IPC分类号： A61K37/14
CPC分类号： A61K38/42 , Y02A50/411
摘要： The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also directed to a method for the treatment of septic shock.

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