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1.发明申请公开(公告)号：US20150157597A1
公开(公告)日：2015-06-11
申请号：US14570625
申请日：2014-12-15
申请人： Jun Tan , Frank Fernandez , Nan Sun , Roland D. Shytle , Jared Ehrhart
发明人： Jun Tan , Frank Fernandez , Nan Sun , Roland D. Shytle , Jared Ehrhart
IPC分类号： A61K31/353 , A61K31/4745
CPC分类号： A61K31/353 , A01K2267/0318 , A61K31/4745 , A61K36/82 , C12N2740/16111 , C12N2740/16311
摘要： The invention relates to treatment of neurodegenerative diseases with JAK/STAT pathway inhibitors to eliminate extracellular cell signaling events leading to cell cycle abrogation and/or apoptosis. Primary neurons were administered neurotoxic proteins, such as gp120, Tat, or gp120 and Tat, with or without IFN-γ added, resulting in neuronal death, and simulated neurodegenerative diseases. The neurodegenerative disease is treated using a JAK/STAT pathway inhibitor, including (-)-epigallocatechin-3-gallate (EGCG), to modulate JAK1 or STAT1 phosphorylation, resulting in resistance to gp120 or Tat neurotoxicity. The invention may be used to treat neurons afflicted with HIV-associated Dementia, multiple sclerosis, Alzheimer's Disease, Parkinson's Disease, amyotrophic lateral sclerosis, or Pick's Disease, and may act in conjunction with antiviral treatment, like HAART.
摘要翻译： 本发明涉及用JAK / STAT途径抑制剂治疗神经变性疾病，以消除导致细胞周期消除和/或凋亡的细胞外细胞信号传导事件。 主要神经元被施用神经毒性蛋白质，例如gp120，Tat或gp120和Tat，加入或不加入IFN-γ，导致神经元死亡和模拟的神经变性疾病。 神经变性疾病使用JAK / STAT途径抑制剂（包括（ - ） - 表没食子儿茶素-3-没食子酸酯（EGCG））来调节JAK1或STAT1磷酸化，导致抗gp120或Tat神经毒性。 本发明可用于治疗患有HIV相关性痴呆，多发性硬化，阿尔茨海默氏病，帕金森病，肌萎缩性侧索硬化或皮克病的神经元，并且可以与抗病毒治疗一起起作用，如HAART。
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2.发明申请公开(公告)号：US20100267733A1
公开(公告)日：2010-10-21
申请号：US12772732
申请日：2010-05-03
申请人： Roland D. Shytle , Jun Tan , Jared Ehrhart
发明人： Roland D. Shytle , Jun Tan , Jared Ehrhart
IPC分类号： A61K31/352 , A61K31/465 , A61K31/4439 , A61K31/505 , A61K31/4965 , A61K31/4985 , A61P29/00 , A61P25/00 , A61P25/16 , A61P25/28
CPC分类号： A61K45/06 , A61K31/05 , A61K31/352 , A61K31/465 , A61K2300/00
摘要： Treatment of microglial cells with nicotine and THC synergistically attenuate the microglial activation. Using microglial activation, the combination of THC and nicotine interact synergistically reduced LPS induced TNF-α release, showing that the combination of THC and nicotine clinically have greater efficacy in reducing neuroinflammation with less side effects than either drug given alone. CD40 signaling was found critically involved in pathological activation of microglial cells. This invention is also relevant to peripheral inflammation as well thru macrophages. In addition, other cannabinoids and other nicotinic-like medications currently in development are also covered under this discovery.
摘要翻译： 用尼古丁和THC治疗小神经胶质细胞协同减弱小胶质细胞的活化。 使用小胶质细胞激活，THC和尼古丁的组合相互作用协同降低LPS诱导的TNF-α释放，表明THC和尼古丁的组合在减少神经炎症方面具有更大的功效，副作用少于单独给药的药物。 CD40信号传导被严重影响小胶质细胞的病理活化。 本发明也与周围炎症以及巨噬细胞相关。 此外，目前正在开发的其他大麻素和其他类似烟碱的药物也涵盖在此发现之下。
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3.发明申请公开(公告)号：US20100069479A1
公开(公告)日：2010-03-18
申请号：US12552715
申请日：2009-09-02
申请人： Jun Tan , Frank Fernandez , Nan Sun , Roland D. Shytle , Jared Ehrhart
发明人： Jun Tan , Frank Fernandez , Nan Sun , Roland D. Shytle , Jared Ehrhart
IPC分类号： A61K31/352 , C12N5/00 , A61P25/00
CPC分类号： A61K31/353 , A01K2267/0318 , A61K31/4745 , A61K36/82 , C12N2740/16111 , C12N2740/16311
摘要： The invention relates to treatment of neurodegenerative diseases with JAK/STAT pathway inhibitors to eliminate extracellular cell signaling events leading to cell cycle abrogation and/or apoptosis. Primary neurons were administered neurotoxic proteins, such as gp120, Tat, or gp120 and Tat, with or without IFN-γ added, resulting in neuronal death, and simulated neurodegenerative diseases. The neurodegenerative disease is treated using a JAK/STAT pathway inhibitor, including (—)-epigallocatechin-3-gallate (EGCG), to modulate JAK1 or STAT1 phosphorylation, resulting in resistance to gp120 or Tat neurotoxicity. The invention may be used to treat neurons afflicted with HIV-associated Dementia, multiple sclerosis, Alzheimer's Disease, Parkinson's Disease, amyotrophic lateral sclerosis, or Pick's Disease, and may act in conjunction with antiviral treatment, like HAART.
摘要翻译： 本发明涉及用JAK / STAT途径抑制剂治疗神经变性疾病，以消除导致细胞周期消除和/或凋亡的细胞外细胞信号传导事件。 主要神经元被施用神经毒性蛋白质，例如gp120，Tat或gp120和Tat，加入或不加入IFN-γ，导致神经元死亡和模拟的神经变性疾病。 神经变性疾病使用JAK / STAT途径抑制剂（包括（ - ） - 表没食子儿茶素-3-没食子酸酯（EGCG））来调节JAK1或STAT1磷酸化，导致抗gp120或Tat神经毒性。 本发明可用于治疗患有HIV相关性痴呆，多发性硬化，阿尔茨海默氏病，帕金森病，肌萎缩性侧索硬化或皮克病的神经元，并且可以与抗病毒治疗一起起作用，如HAART。
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公开(公告)号：US10130708B2
公开(公告)日：2018-11-20
申请号：US14007023
申请日：2012-03-26
申请人： Michael John Zaworotko , Roland D. Shytle , Tien Teng Ong , Ryan N. Cantwell , Tranhha Nguyen , Adam John Smith , Padmini Kavuru
发明人： Michael John Zaworotko , Roland D. Shytle , Tien Teng Ong , Ryan N. Cantwell , Tranhha Nguyen , Adam John Smith , Padmini Kavuru
摘要： 2:1 cocrystals of amino acids and Li+ salts crystallize from hot water to afford water stable cationic networks based upon tetrahedral lithium cations: bilayered square grids, a lithium zeolitic metal-organic material (LiZMOM) and several lithium diamondoid metal-organic materials (LiDMOMs). The compositions may be used as a pharmaceutical for the treatment of suicidality and other disorders that require lithium to penetrate the blood brain barrier and exert therapeutic effects in the CNS. Advantageously, the novel cocrystal forms described herein may be used to lower the oral dose required to achieve therapeutic concentrations of lithium in the brain, thus reducing the peripheral toxicity and potentially broadening the therapeutic index in comparison to conventional lithium forms.
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公开(公告)号：US20140242193A1
公开(公告)日：2014-08-28
申请号：US14007023
申请日：2012-03-26
申请人： Michael John Zaworotko , Roland D. Shytle , Tien Teng Ong , Padmini Kavuru , Ryan N. Cantwell , Tranhha Nguyen , Adam John Smith
发明人： Michael John Zaworotko , Roland D. Shytle , Tien Teng Ong , Padmini Kavuru , Ryan N. Cantwell , Tranhha Nguyen , Adam John Smith
CPC分类号： A61K47/183 , A61K9/145 , A61K33/00 , A61K33/14 , A61K45/06 , A61K47/186 , A61K47/22 , A61K2300/00
摘要： 2:1 cocrystals of amino acids and Li+ salts crystallize from hot water to afford water stable cationic networks based upon tetrahedral lithium cations: bilayered square grids, a lithium zeolitic metal-organic material (LiZMOM) and several lithium diamondoid metal-organic materials (LiDMOMs). The compositions may be used as a pharmaceutical for the treatment of suicidality and other disorders that require lithium to penetrate the blood brain barrier and exert therapeutic effects in the CNS. Advantageously, the novel cocrystal forms described herein may be used to lower the oral dose required to achieve therapeutic concentrations of lithium in the brain, thus reducing the peripheral toxicity and potentially broadening the therapeutic index in comparison to conventional lithium forms.
摘要翻译： 2:1的氨基酸和Li +盐的共晶体从热水中结晶，得到基于四面体锂阳离子的水稳定的阳离子网络：双层方形网格，锂沸石金属有机材料（LiZMOM）和几种锂金刚石金属有机材料（LiDMOM ）。 该组合物可用作治疗需要锂透过血脑屏障并在CNS中发挥治疗效果的自杀性和其它障碍的药物。 有利地，本文所述的新型共结晶形式可用于降低在脑中实现治疗浓度的锂所需的口服剂量，从而与常规的锂形式相比降低外周毒性并可能拓宽治疗指数。
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公开(公告)号：US06979698B1
公开(公告)日：2005-12-27
申请号：US09526403
申请日：2000-03-15
IPC分类号： A61K31/13
CPC分类号： A61K31/13
摘要： The treatment of learning, memory, and age-related memory disorders includes administration of a nicotine antagonist. The preferred nicotine antagonists are mecamylamine, a mecamylamine analog, or a mecamylamine stereoisomer. The effective amount of the nicotine antagonist is 0.005–1.00 mg/kg/day. Alternatively, the method utilizes a partial nicotine agonist.
摘要翻译： 学习，记忆和年龄相关记忆障碍的治疗包括施用尼古丁拮抗剂。 优选的尼古丁拮抗剂是美加明胺，美加明胺类似物或美加明胺立体异构体。 尼古丁拮抗剂的有效量为0.005-1.00mg / kg /天。 或者，该方法利用部分尼古丁激动剂。
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7.发明授权
公开(公告)号：US6034079A
公开(公告)日：2000-03-07
申请号：US198882
申请日：1998-11-23
IPC分类号： A61K31/13 , A61K31/445 , A61K31/505 , A61K31/54
CPC分类号： A61K31/13 , A61K31/445 , A61K31/505 , A61K31/54
摘要： Nicotine-responsive neuropsychiatric disorders can be treated by administering a nicotine antagonist, particularly mecamylamine. Combination therapy of mecamylamine with a neuroleptic drug also is disclosed. The neuropsychiatric disorders include Tourette's syndrome, schizophrenia, depression, bipolar disorder, tremors, attention deficit hyperactivity disorder, obsessive-compulsive disorder, hemidystonia, rage outbursts and tardive dyskinesia.
摘要翻译： 可以通过施用尼古丁拮抗剂，特别是美加明胺来治疗尼古丁反应性神经精神障碍。 麦考胺与精神安定药联合治疗也被公开。 神经精神障碍包括Tourette综合征，精神分裂症，抑郁症，双相情感障碍，震颤，注意缺陷多动障碍，强迫症，hemidystonia，愤怒爆发和迟发性运动障碍。
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