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1. 发明授权

US06187756B1 Composition and methods for treatment of neurological disorders and neurodegenerative diseases 有权
标题翻译：用于治疗神经障碍和神经变性疾病的组合物和方法
公开(公告)号：US06187756B1
公开(公告)日：2001-02-13
申请号：US09493228
申请日：2000-01-28
申请人： Robert K. K. Lee , Richard J. Wurtman
发明人： Robert K. K. Lee , Richard J. Wurtman
IPC分类号： A61K3170
CPC分类号： A61K31/7076 , A61K31/00 , A61K31/05 , A61K31/137 , A61K31/18 , A61K31/198 , A61K31/34 , A61K31/365 , A61K31/436 , A61K31/465 , A61K31/5383 , A61K31/5575 , A61K38/13 , A61K38/193 , Y10S514/878 , Y10S514/879
摘要： It has been discovered that the stimulation of &bgr;-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising &bgr;-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by &bgr;-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of &bgr;-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, forskolin, or nicotine ditartrate is inhibited by immunosuppressants or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium/calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.
摘要翻译：已经发现，激活cAMP形成的β-肾上腺素能受体的刺激在星形胶质细胞中产生增加的APP和GFAP合成。因此，神经元细胞体外暴露于包含β-肾上腺素能受体配体或激动剂（包括例如去甲肾上腺素，异丙肾上腺素等）的某些组合物的体外或体内暴露增加APP mRNA转录和随后的APP过量产生。这些增加被β-肾上腺素能受体拮抗剂如普萘洛尔阻断。用8Br-cAMP，前列腺素E2（PG E2），毛喉素和烟碱尼泊金酯处理这些细胞的体外或体内治疗也增加了APP合成，包括mRNA和蛋白水平的增加，以及表达增加胶质纤维酸性蛋白（GFAP）。公开了通过cAMP信号传导或β-肾上腺素能受体活化调节APP过表达和介导反应性星形胶质细胞增多的组合物和方法。还发现免疫抑制剂或抗炎剂如环孢菌素A和FK-506（他克莫司）也抑制了由8Br-cAMP，PG E2，毛喉素或烟碱酒石酸引起的APP合成的增加作为离子通道调节剂，包括离子螯合剂如EGTA或钙/钙调蛋白激酶抑制剂，例如KN93。本发明在减轻，治疗或预防神经障碍和神经变性疾病（包括阿尔茨海默病）方面具有广泛的意义。

2. 发明授权

US06333317B1 Regulation of amyloid precursor protein (APP) expression by administration of an estrogenic compound 失效
标题翻译：通过施用雌激素化合物调节淀粉样蛋白前体蛋白（APP）表达
公开(公告)号：US06333317B1
公开(公告)日：2001-12-25
申请号：US09049198
申请日：1998-03-27
申请人： Robert K. K. Lee , Richard J. Wurtman
发明人： Robert K. K. Lee , Richard J. Wurtman
IPC分类号： A01N3736
CPC分类号： A61K31/566 , A61K31/00 , A61K31/565
摘要： It has been discovered that lipophilic hormones that interact with cytosolic or nuclear receptors regulate APP expression and synthesis, through modification of APP mRNA stability and/or regulation of APP gene transcription and translation activities. These studies demonstrate that the treatment of brain cells with estrone or 17&bgr;-estradiol results in a reduction in the level of APP holoprotein expression, without a concomitant change in the total level of cell protein. The reduction in the level of APP holoprotein caused by estrone or 17&bgr;-estradiol is also expected to reduce the production of neurotoxic APP fragments. In as much as estrogen deficiency in postmenopausal women is associated with a higher incidence of Alzheimer's disease, this discovery opens the possibility that estrogen therapy may prevent some of the neurodegenerative and cognitive changes associated with Alzheimer's disease, aging and other disease conditions associated with such neurodegenerative and cognitive decline.
摘要翻译：已经发现，通过修饰APP mRNA稳定性和/或调节APP基因转录和翻译活性，与胞质或核受体相互作用的亲脂性激素调节APP表达和合成。这些研究表明，使用雌酮或17β-雌二醇治疗脑细胞导致APP蛋白表达水平的降低，而细胞蛋白总水平没有伴随的变化。由雌酮或17β-雌二醇引起的APP蛋白水平的降低也有望降低神经毒性APP片段的产生。绝经后妇女的雌激素缺乏与阿尔茨海默病的发病率相关，这一发现揭示了雌激素治疗可能会预防与阿尔茨海默氏病相关的一些神经变性和认知变化，老年化和其他与这种神经变性相关的疾病状况和认知衰退。

3. 发明授权

US06184248B2 Compositions and methods for treatment of neurological disorders and neurodegenerative diseases 有权
标题翻译：用于治疗神经障碍和神经变性疾病的组合物和方法
公开(公告)号：US06184248B2
公开(公告)日：2001-02-06
申请号：US09435470
申请日：1999-11-08
申请人： Robert K. K. Lee , Richard J. Wurtman
发明人： Robert K. K. Lee , Richard J. Wurtman
IPC分类号： A61K3134
CPC分类号： A61K31/00 , A61K31/05 , A61K31/137 , A61K31/18 , A61K31/198 , A61K31/34 , A61K31/365 , A61K31/436 , A61K31/465 , A61K31/5383 , A61K31/5575 , A61K31/7076 , A61K38/13 , A61K38/193
摘要： It has been discovered that the stimulation of &bgr;adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising &bgr;-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by &bgr;-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of &bgr;-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, or forskolin is inhibited by immunosuppressants, immunophilin ligands, or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium/calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.
摘要翻译：已经发现，激活cAMP形成的β-肾上腺素能受体的刺激在星形胶质细胞中产生增加的APP和GFAP合成。因此，神经元细胞体外暴露于包含β-肾上腺素能受体配体或激动剂（包括例如去甲肾上腺素，异丙肾上腺素等）的某些组合物的体外或体内暴露增加APP mRNA转录和随后的APP过量产生。这些增加被β-肾上腺素能受体拮抗剂如普萘洛尔阻断。用8Br-cAMP，前列腺素E2（PG E2），毛喉素和烟碱尼泊金酯处理这些细胞的体外或体内治疗也增加了APP合成，包括mRNA和蛋白水平的增加，以及表达增加胶质纤维酸性蛋白（GFAP）。公开了通过cAMP信号传导或β-肾上腺素能受体活化调节APP过表达和介导反应性星形胶质细胞增多的组合物和方法。进一步发现，由8Br-cAMP，PG E2或毛喉素引起的APP合成的增加被免疫抑制剂，免疫亲和素配体或抗炎剂如环孢菌素A和FK-506（他克莫司）抑制，作为以及离子通道调节剂，包括离子螯合剂如EGTA或钙/钙调蛋白激酶抑制剂，例如KN93。本发明在减轻，治疗或预防神经障碍和神经变性疾病（包括阿尔茨海默病）方面具有广泛的意义。

4. 发明授权

US6043224A Compositions and methods for treatment of neurological disorders and neurodegenerative diseases 失效
标题翻译：用于治疗神经障碍和神经变性疾病的组合物和方法
公开(公告)号：US6043224A
公开(公告)日：2000-03-28
申请号：US924505
申请日：1997-09-05
申请人： Robert K. K. Lee , Richard J. Wurtman
发明人： Robert K. K. Lee , Richard J. Wurtman
IPC分类号： A61K31/00 , A61K31/05 , A61K31/137 , A61K31/18 , A61K31/198 , A61K31/34 , A61K31/365 , A61K31/436 , A61K31/465 , A61K31/5383 , A61K31/5575 , A61K38/13 , A61K38/19 , A61K3/705
CPC分类号： A61K31/7076 , A61K31/00 , A61K31/05 , A61K31/137 , A61K31/18 , A61K31/198 , A61K31/34 , A61K31/365 , A61K31/436 , A61K31/465 , A61K31/5383 , A61K31/5575 , A61K38/13 , A61K38/193 , Y10S514/878 , Y10S514/879
摘要： It has been discovered that the stimulation of .beta.-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising .beta.-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by .beta.-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E.sub.2 (PG E.sub.2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of .beta.-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E.sub.2, forskolin, or nicotine ditartrate is inhibited by immunosuppressants or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium/calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.
摘要翻译：已经发现，激活cAMP形成的β-肾上腺素能受体的刺激在星形胶质细胞中产生增加的APP和GFAP合成。因此，神经元细胞体外或体内暴露于包含β-肾上腺素能受体配体或激动剂（包括例如去甲肾上腺素，异丙肾上腺素等）的某些组合物会增加APP mRNA转录和随后的APP过量产生。这些增加被β-肾上腺素能受体拮抗剂如普萘洛尔阻断。用8Br-cAMP，前列腺素E2（PG E2），毛喉素和烟碱尼泊金酯处理这些细胞的体外或体内治疗也增加了APP合成，包括mRNA和蛋白水平的增加，以及表达增加胶质纤维酸性蛋白（GFAP）。公开了通过cAMP信号传导或β-肾上腺素能受体活化调节APP过表达和介导反应性星形胶质细胞增生的组合物和方法。还发现免疫抑制剂或抗炎剂如环孢菌素A和FK-506（他克莫司）抑制了由8Br-cAMP，PG E2，毛喉素或烟碱尼泊金酯引起的APP合成的增加，以及作为离子通道调节剂，包括离子螯合剂如EGTA或钙/钙调蛋白激酶抑制剂，例如KN93。本发明在减轻，治疗或预防神经障碍和神经变性疾病（包括阿尔茨海默病）方面具有广泛的意义。

5. 发明授权

US10086009B2 Compositions containing pufa and/or uridine and methods of use thereof 有权
公开(公告)号：US10086009B2
公开(公告)日：2018-10-02
申请号：US11920915
申请日：2006-05-23
申请人： Richard J. Wurtman , Ingrid Richardson
发明人： Richard J. Wurtman , Ingrid Richardson
IPC分类号： A01N57/26 , A61K31/685 , A61K31/7072 , A61K31/202 , A61K31/14
摘要： This invention provides methods of enhancing brain development; increasing or enhancing intelligence; increasing or enhancing synthesis and levels of phospholipids, synapses, synaptic proteins, and synaptic membranes by a neural cell or brain cell, comprising contacting a subject or a pregnant or nursing mother thereof with a composition comprising an omega-3 fatty acid, an omega-6 fatty acid, and/or uridine, a metabolic precursor thereof, or a combination thereof.

6. 发明申请

US20100022567A1 Compositions containing pufa and/or uridine and methods of use thereof 审中-公开
标题翻译：含有pufa和/或尿苷的组合物及其使用方法
公开(公告)号：US20100022567A1
公开(公告)日：2010-01-28
申请号：US11920915
申请日：2006-05-23
申请人： Richard J. Wurtman , Ingrid Richardson
发明人： Richard J. Wurtman , Ingrid Richardson
IPC分类号： A61K31/506 , A61K31/20 , A61P25/00
CPC分类号： A61K31/7072 , A61K31/14 , A61K31/202 , A61K2300/00
摘要： This invention provides methods of enhancing brain development; increasing or enhancing intelligence; increasing or enhancing synthesis and levels of phospholipids, synapses, synaptic proteins, and synaptic membranes by a neural cell or brain cell, comprising contacting a subject or a pregnant or nursing mother thereof with a composition comprising an omega-3 fatty acid, an omega-6 fatty acid, and/or uridine, a metabolic precursor thereof, or a combination thereof.
摘要翻译：本发明提供增强脑发育的方法; 增加或加强智力; 通过神经细胞或脑细胞增加或增强磷脂，突触，突触蛋白和突触膜的合成和水平，包括使受试者或其孕妇或哺乳母亲与包含ω-3脂肪酸，ω- 6脂肪酸和/或尿苷，其代谢前体，或其组合。

7. 发明授权

US07011857B2 Weight loss compositions and methods for individuals who may have gastric hyperacidity 有权
公开(公告)号：US07011857B2
公开(公告)日：2006-03-14
申请号：US10096108
申请日：2002-03-13
申请人： Judith J. Wurtman , Richard J. Wurtman
发明人： Judith J. Wurtman , Richard J. Wurtman
IPC分类号： A23L1/0522 , A23L1/09
CPC分类号： A23L33/22 , A23L5/00 , A23L7/00 , A23L9/00 , A23L9/12 , A23L21/00 , A23L29/212 , A23L29/30 , A23L29/35 , A23L33/125 , A23L33/15 , A23L33/155 , A23L33/30 , A23L33/40 , A23V2002/00 , Y10S426/804 , Y10S426/808 , Y10S426/81 , A23V2250/5118 , A23V2250/5114 , A23V2250/061 , A23V2250/1578 , A23V2250/161 , A23V2250/70 , A23V2250/5108
摘要： Compositions and methods of losing weight are described that are suitable for individuals susceptible to gastric hyperacidity or gastroesophageal reflux. The compositions include in part a snack food having two or more rapidly digestible carbohydrates, in which the foodstuff or an aqueous mixture of the foodstuff and water has a pH equal to or greater than about 6, and in which the snack is substantially protein-free. The method of weight loss suitable for an individual with gastric hyperacidity includes substantially limiting the individual's caloric intake to about 1400 calories or less for women and 1800 calories or less for men in which the caloric intake includes one or more substantially protein-free snack foodstuffs having two or more rapidly digestible carbohydrates, in which an aqueous mixture of the foodstuff with water has a pH equal to or greater than about 6 and in which the individual loses weight.

8. 发明授权

US5449683A Methods of inducing sleep using melatonin 失效
标题翻译：使用褪黑激素诱导睡眠的方法
公开(公告)号：US5449683A
公开(公告)日：1995-09-12
申请号：US93317
申请日：1993-07-16
申请人： Richard J. Wurtman
发明人： Richard J. Wurtman
IPC分类号： A61K31/40 , A61K31/403 , A61K31/404 , A61K31/4045 , A61P25/20 , C07D209/16 , A61K31/405
CPC分类号： A61K31/4045 , A61K31/40 , Y10S514/923
摘要： Methods of inducing sleepiness and sleep in an individual by administering to that individual a single dose of melatonin sufficient to induce sleepiness and sleep in the individual.
摘要翻译：通过向个体施用足以诱导个体嗜睡和睡眠的单剂量的褪黑激素来诱导个体中的嗜睡和睡眠的方法。

9. 发明授权

US5019594A Method for decreasing appetite 失效
标题翻译：降低食欲的方法
公开(公告)号：US5019594A
公开(公告)日：1991-05-28
申请号：US442011
申请日：1989-11-28
申请人： Richard J. Wurtman , Timothy J. Maher
发明人： Richard J. Wurtman , Timothy J. Maher
IPC分类号： A61K31/135 , A61K31/137 , A61K31/195 , A61K31/198 , A61K45/06 , A61P3/04 , A61P25/02
CPC分类号： A61K31/195
摘要： A composition for decreasing appetite comprising an indirect-acting sympathomimetic drug and tyrosine or a tyrosine precursor. The drug may be phenylpropanolamine, amphetamine, or ephedrine. The tyrosine enhances the known appetite-suppressing activity of the drug.
摘要翻译：一种用于降低食欲的组合物，其包含间接作用的拟交感神经药物和酪氨酸或酪氨酸前体。药物可以是苯丙醇胺，苯丙胺或麻黄碱。酪氨酸增强了药物已知的食欲抑制活性。

10. 发明授权

US4885312A Method for enhancing the effect of indirect-acting sympathomimetic amines 失效
标题翻译：增强间接作用交感神经胺作用的方法
公开(公告)号：US4885312A
公开(公告)日：1989-12-05
申请号：US947208
申请日：1986-12-29
申请人： Richard J. Wurtman , Timothy J. Maher
发明人： Richard J. Wurtman , Timothy J. Maher
IPC分类号： A61K31/195
CPC分类号： A61K31/195
摘要： Tyrosine or a tyrosine precursor is administered concomitantly with an indirect-acting sympathomimetic amine drug to increase the level of norepinephrine that can be released in sympathetic neuron synapses.
摘要翻译：酪氨酸或酪氨酸前体与间接作用的拟交感神经胺药物同时施用，以增加可在交感神经元突触中释放的去甲肾上腺素水平。

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