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1. 发明授权

US06696408B1 Contulakin-G, analogs thereof and uses therefor 有权
公开(公告)号：US06696408B1
公开(公告)日：2004-02-24
申请号：US09606247
申请日：2000-06-29
申请人： A. Grey Craig , David Griffen , Baldomero M. Olivera , Maren Watkins , David R. Hillyard , Julita Imperial , Lourdes J. Cruz , John D. Wagstaff , Richard T. Layer , Robert M. Jones , R. Tyler McCabe
发明人： A. Grey Craig , David Griffen , Baldomero M. Olivera , Maren Watkins , David R. Hillyard , Julita Imperial , Lourdes J. Cruz , John D. Wagstaff , Richard T. Layer , Robert M. Jones , R. Tyler McCabe
IPC分类号： A01N3718
CPC分类号： C07K7/08 , A61K38/00 , C07K9/001 , C07K14/575
摘要： The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.

2. 发明授权

US06489298B1 Contulakin-G, analogs thereof and uses thereof 有权
标题翻译： Contulakin-G，其类似物及其用途
公开(公告)号：US06489298B1
公开(公告)日：2002-12-03
申请号：US09605991
申请日：2000-06-29
申请人： A. Grey Craig , David Griffen , Baldomero M. Olivera , Maren Watkins , David R. Hillyard , Julita Imperial , Lourdes J. Cruz , John D. Wagstaff , Richard T. Layer , Robert M. Jones , R. Tyler McCabe
发明人： A. Grey Craig , David Griffen , Baldomero M. Olivera , Maren Watkins , David R. Hillyard , Julita Imperial , Lourdes J. Cruz , John D. Wagstaff , Richard T. Layer , Robert M. Jones , R. Tyler McCabe
IPC分类号： A61K3800
CPC分类号： C07K7/08 , A61K38/00 , C07K9/001 , C07K14/575
摘要： The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.
摘要翻译：本发明涉及到编码该成熟肽的前体的cDNA克隆的contulakin-G（其是天然糖基化肽），去糖基化的连翘蛋白-G（称为Thr10-contulakin-G）及其衍生物，以及到前体肽。本发明进一步涉及该肽作为抗癫痫发作，抗炎，抗休克，抗血栓，降血压，止痛，抗精神病，帕金森病，胃肠道疾病，抑郁状态，认知功能障碍焦虑症，迟发性运动障碍，药物依赖性，恐慌发作，躁狂症，肠易激综合征，腹泻，溃疡，胃肠道肿瘤，杜氏综合征，亨廷顿氏舞蹈病，血管渗漏，抗动脉硬化，血管和血管舒张障碍以及神经系统，神经功能和神经精神药理学障碍。

3. 发明授权

US06344551B1 Contulakin-G, analogs thereof and uses therefor 有权
标题翻译： Contulakin-G，其类似物和用途
公开(公告)号：US06344551B1
公开(公告)日：2002-02-05
申请号：US09605990
申请日：2000-06-29
申请人： A. Grey Craig , David Griffin , Baldomero M. Olivera , Maren Watkins , David R. Hillyard , Julita Imperial , Lourdes J. Cruz , John D. Wagstaff , Richard T. Layer , Robert M. Jones , R. Tyler McCabe
发明人： A. Grey Craig , David Griffin , Baldomero M. Olivera , Maren Watkins , David R. Hillyard , Julita Imperial , Lourdes J. Cruz , John D. Wagstaff , Richard T. Layer , Robert M. Jones , R. Tyler McCabe
IPC分类号： C12N1512
CPC分类号： C07K7/08 , A61K38/00 , C07K9/001 , C07K14/575
摘要： The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.
摘要翻译：本发明涉及到编码该成熟肽的前体的cDNA克隆的contulakin-G（其是天然糖基化肽），去糖基化的连翘蛋白-G（称为Thr10-contulakin-G）及其衍生物，以及到前体肽。本发明进一步涉及该肽作为抗癫痫发作，抗炎，抗休克，抗血栓，降血压，止痛，抗精神病，帕金森病，胃肠道疾病，抑郁状态，认知功能障碍焦虑症，迟发性运动障碍，药物依赖性，恐慌发作，躁狂症，肠易激综合征，腹泻，溃疡，胃肠道肿瘤，杜氏综合征，亨廷顿氏舞蹈病，血管渗漏，抗动脉硬化，血管和血管舒张障碍以及神经系统，神经功能和神经精神药理学障碍。

4. 发明授权

US06515103B1 Conantokins 失效
标题翻译：柯南托克斯
公开(公告)号：US06515103B1
公开(公告)日：2003-02-04
申请号：US09142080
申请日：2000-05-11
申请人： Fe C. Abogadie , Lourdes J. Cruz , Baldomero M. Olivera , Craig Walker , Clark Colledge , David R. Hillyard , Elsie Jimenez , Richard T. Layer , Li-Ming Zhou , Gregory S. Shen , R. Tyler McCabe , Jean E. Rivier
发明人： Fe C. Abogadie , Lourdes J. Cruz , Baldomero M. Olivera , Craig Walker , Clark Colledge , David R. Hillyard , Elsie Jimenez , Richard T. Layer , Li-Ming Zhou , Gregory S. Shen , R. Tyler McCabe , Jean E. Rivier
IPC分类号： A61K3800
CPC分类号： C07K14/43504 , A61K38/00
摘要： The present invention is directed to conantokin peptides, conantokin peptide derivatives and conantokin peptide chimeras, referred to collectively as conantokins, having 10-30 amino acids, including preferably two or more &ggr;-carboxyglutamic acid residues. The conantokins are useful for the treatment of neurologic and psychiatric disorders, such as anticonvulsant agents, neuroprotective agents or analgesic agents.
摘要翻译：本发明涉及具有10-30个氨基酸，包括优选两个或更多个γ-羧基谷氨酸残基的组合蛋白肽，柯南多肽衍生物和柯南鸟肽嵌合体，统称为聚对二聚体。凝血因子可用于治疗神经和精神疾病，例如抗惊厥剂，神经保护剂或止痛剂。

5. 发明授权

US06277825B1 Use of conantokins for treating pain 失效
标题翻译：使用柯南金治疗疼痛
公开(公告)号：US06277825B1
公开(公告)日：2001-08-21
申请号：US09357141
申请日：1999-07-20
申请人： Baldomero M. Olivera , J. Michael McIntosh , R. Tyler McCabe , Richard T. Layer , Li-Ming Zhou
发明人： Baldomero M. Olivera , J. Michael McIntosh , R. Tyler McCabe , Richard T. Layer , Li-Ming Zhou
IPC分类号： A61K3800
CPC分类号： C07K14/43504 , A61K38/00
摘要： The present invention is directed to the use of conantokin peptides, conantokin peptide derivatives and conantokin peptide chimeras, referred to collectively as conantokins, having 10-30 amino acids, including preferably two or more &ggr;-carboxyglutamic acid residues, for the treatment of neurologic and psychiatric disorders, such as pain, e.g., as an analgesic agent.
摘要翻译：本发明涉及使用具有10-30个氨基酸，包括优选两个或更多个γ-羧基谷氨酸残基的共同称为聚对二聚腺嘌呤肽，柯南多肽衍生物和柯南多肽嵌合体用于治疗神经病学和精神疾病如疼痛，例如止痛剂。

6. 发明授权

US06399574B1 Use of conantokins 失效
标题翻译：使用柯南金
公开(公告)号：US06399574B1
公开(公告)日：2002-06-04
申请号：US09533889
申请日：2000-03-22
申请人： R. Tyler McCabe , Li-Ming Zhou , Richard T. Layer , Baldomero M. Olivera , J. Michael McIntosh
发明人： R. Tyler McCabe , Li-Ming Zhou , Richard T. Layer , Baldomero M. Olivera , J. Michael McIntosh
IPC分类号： A61K3800
CPC分类号： C07K14/43504 , A61K38/00
摘要： The present invention is directed to the use of conantokin peptides, conantokin peptide derivatives and conantokin peptide chimeras, referred to collectively as conantokins, having 10-30 amino acids, including preferably two or more &ggr;-carboxyglutamic acid residues, for the treatment of neurologic and psychiatric disorders, such as anticonvulsant agents, neuroprotective agents or analgesic agents. Neurologic disorders and psychiatric disorders include, epilepsy, convulsions, neurotoxic injury (associated with conditions of hypoxia, anoxia or ischemia which typically follows stroke, cerebrovascular accident, brain or spinal cord trauma, myocardial infarct, physical trauma, drowning, suffocation, perinatal asphyxia, or hypoglycemic events), neurodegeneration (associated with Alzheimer's disease, senile dementia, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease, schizophrenia, AIDS dementia, multi-infarct dementia, Binswanger dementia and neuronal damage associated with uncontrolled seizures), chemical toxicity (such as addiction, morphine tolerance, opiate tolerance, opioid tolerance and barbiturate tolerance), pain (acute, chronic, migraine), anxiety, major depression, manic-depressive illness, obsessive-complusive disorder, schizophrenia and mood disorders (such as bipolar disorder, unipolar depression, dysthymia and seasonal effective disorder) and dystonia (movement disorder), sleep disorder, muscle relaxation and urinary incontinence. In addition, the conantokins are useful for treating HIV infection, ophthalmic indications and memory, learning or cognitive deficits.
摘要翻译：本发明涉及使用具有10-30个氨基酸，包括优选两个或更多个γ-羧基谷氨酸残基的共同称为聚对二聚腺嘌呤肽，柯南多肽衍生物和柯南多肽嵌合体用于治疗神经病学和精神障碍，如抗惊厥剂，神经保护剂或止痛剂。神经系统疾病和精神障碍包括癫痫，惊厥，神经毒性损伤（与缺氧，缺氧或局部缺血，脑卒中，脑或脊髓创伤，心肌梗塞，身体创伤，溺水，窒息，围产期窒息，或低血糖事件），神经变性（与阿尔茨海默病，老年性痴呆，肌萎缩性侧索硬化症，多发性硬化症，帕金森氏病，亨廷顿病，唐氏综合征，柯萨科夫病，精神分裂症，艾滋病痴呆，多发性梗塞性痴呆，Binswanger痴呆和神经元损伤有关不安全的癫痫发作），化学毒性（如成瘾，吗啡耐受，阿片剂耐受性，阿片样物质耐受性和巴比妥耐受性），疼痛（急性，慢性，偏头痛），焦虑，重性抑郁症，躁狂抑郁症，强迫症 - 精神分裂症和情绪障碍（如双相情感障碍，单极痴呆）肌力障碍和季节性有效障碍）和肌张力障碍（运动障碍），睡眠障碍，肌肉松弛和尿失禁。此外，凝血因子可用于治疗艾滋病毒感染，眼科指征和记忆，学习或认知缺陷。

7. 发明授权

US06172041B2 Use of conantokins 失效
标题翻译：使用柯南金
公开(公告)号：US06172041B2
公开(公告)日：2001-01-09
申请号：US09142078
申请日：1999-02-10
申请人： R. Tyler McCabe , Li-Ming Zhou , Richard T. Layer , Baldomero M. Olivera , J. Michael McIntosh
发明人： R. Tyler McCabe , Li-Ming Zhou , Richard T. Layer , Baldomero M. Olivera , J. Michael McIntosh
IPC分类号： A61K3800
CPC分类号： C07K14/43504 , A61K38/00
摘要： The present invention is directed to the use of conantokin peptides, conantokin peptide derivatives and conantokin peptide chimeras, referred to collectively as conantokins, having 10-30 amino acids, including preferably two or more &ggr;-carboxyglutamic acid residues, for the treatment of neurologic and psychiatric disorders, such as anticonvulsant agents, neuroprotective agents or analgesic agents. Neurologic disorders and psychiatric disorders include epilepsy, convulsions, neurotoxic injury (associated with conditions of hypoxia, anoxia or ischemia which typically follows stroke, cerebrovascular accident, brain or spinal cord trauma, myocardial infarct, physical trauma, drowning, suffocation, perinatal asphyxia, or hypoglycemic events), neurodegeneration (associated with Alzheimer's disease, senile dementia, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease, schizophrenia, AIDS dementia, multi-infarct dementia, Binswanger dementia and neuronal damage associated with uncontrolled seizures), chemical toxicity (such as addiction, morphine tolerance, opiate tolerance, opioid tolerance and barbiturate tolerance), pain (acute, chronic, migraine), anxiety, major depression, manic-depressive illness, obsessive-compulsive disorder, schizophrenia and mood disorders (such as bipolar disorder, unipolar depression, dysthymia and seasonal effective disorder) and dystonia (movement disorder), sleep disorder, muscle relaxation and urinary incontinence. In addition, the conantokins are useful for treating HIV infection, ophthalmic indications and memory, learning or cognitive deficits.
摘要翻译：本发明涉及使用具有10-30个氨基酸，包括优选两个或更多个γ-羧基谷氨酸残基的共同称为聚对二聚腺嘌呤肽，柯南多肽衍生物和柯南多肽嵌合体用于治疗神经病学和精神障碍，如抗惊厥剂，神经保护剂或止痛剂。神经系统疾病和精神疾病包括癫痫，抽搐，神经毒性损伤（与缺氧，缺氧或局部缺血的症状相关，典型地是中风，脑血管意外，脑或脊髓创伤，心肌梗塞，身体创伤，溺水，窒息，围产期窒息或低血糖事件），神经变性（与阿尔茨海默氏病，老年性痴呆，肌萎缩性侧索硬化，多发性硬化症，帕金森病，亨廷顿病，唐氏综合征，柯萨科夫病，精神分裂症，艾滋病痴呆，多发性梗塞性痴呆，Binswanger痴呆和神经元损伤有关不安全的癫痫发作），化学毒性（如成瘾，吗啡耐受，阿片剂耐受，阿片样物质耐受和巴比妥耐受），疼痛（急性，慢性，偏头痛），焦虑，主要抑郁症，躁狂抑郁症，强迫症，精神分裂症和情绪障碍（如双相情感障碍，单极压抑离子，心境恶劣和季节性有效障碍）和肌张力障碍（运动障碍），睡眠障碍，肌肉松弛和尿失禁。此外，凝血因子可用于治疗艾滋病毒感染，眼科指征和记忆，学习或认知缺陷。

8. 发明授权

US06525021B1 Contulakin-G, analogs thereof and uses therefor 失效
标题翻译： Contulakin-G，其类似物和用途
公开(公告)号：US06525021B1
公开(公告)日：2003-02-25
申请号：US09609534
申请日：2000-06-30
申请人： John D. Wagstaff , R. Tyler McCabe
发明人： John D. Wagstaff , R. Tyler McCabe
IPC分类号： A61K3800
CPC分类号： C07K7/08 , A61K38/00 , C07K9/001 , C07K14/575
摘要： The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for cytoprotection (including neuroprotection and cardioprotection), anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.
摘要翻译：本发明涉及到编码该成熟肽的前体的cDNA克隆的contulakin-G（其是天然糖基化肽），去糖基化的连翘蛋白-G（称为Thr10-contulakin-G）及其衍生物，以及到前体肽。本发明进一步涉及该肽作为细胞保护（包括神经保护和心脏保护），抗癫痫发作，抗炎，抗休克，抗血栓，降血压，镇痛，抗精神病药，帕金森病，胃肠道疾病，抑郁状态，认知功能障碍，焦虑，迟发性运动障碍，药物依赖，恐慌发作，躁狂症，肠易激综合征，腹泻，溃疡，胃肠道肿瘤，图雷特氏综合征，亨廷顿氏舞蹈病，血管渗漏，抗动脉硬化，血管和血管舒张障碍，以及神经系统，神经功能和神经精神药理学疾病。

9. 发明授权

US5503852A Method for making self-assembling diketopiperazine drug delivery system 失效
标题翻译：自组装二酮哌嗪药物输送系统的方法
公开(公告)号：US5503852A
公开(公告)日：1996-04-02
申请号：US299842
申请日：1994-09-01
申请人： Solomon S. Steiner , Christopher A. Rhodes , Gregory S. Shen , R. Tyler McCabe
发明人： Solomon S. Steiner , Christopher A. Rhodes , Gregory S. Shen , R. Tyler McCabe
IPC分类号： C07D319/12 , A61K9/16 , A61K9/50 , A61K47/22 , C07D241/08
CPC分类号： A61K9/1617
摘要： Drug delivery systems have been developed based on the formation of diketopiperazine (or analogs) microparticles. In the preferred embodiment the microparticle is stable at low pH and disintegrates at physiological pH, and is particularly useful for oral drug delivery. In other embodiments, the microparticles are stable at high pH and disintegrate at neutral or basic pH, or are stable at neutral pH and disintegrate at high or low pH. In the most preferred embodiment the microparticles are formed in the presence of the drug to be delivered, for example, insulin, felbamate, calcitonin or heparin. The diketopiperazine synthetic intermediates are preferably formed by cyclodimerization to form diketopiperazine derivatives at elevated temperatures under dehydrating conditions, functionalized on the side chains, and then precipitated with drug to be incorporated into microparticles.
摘要翻译：已经基于二酮哌嗪（或类似物）微粒的形成开发了药物递送系统。在优选的实施方案中，微粒在低pH下是稳定的并且在生理pH下分解，并且对于口服药物递送特别有用。在其它实施方案中，微粒在高pH下是稳定的，并且在中性或碱性pH下分解，或者在中性pH下是稳定的，并在高或低pH下崩解。在最优选的实施方案中，在待递送的药物例如胰岛素，麦芽糖素，降钙素或肝素的存在下形成微粒。二酮哌嗪合成中间体优选通过环二聚作用形成二酮哌嗪衍生物，在脱水条件下在侧链官能化的高温下形成二酮哌嗪衍生物，然后用药物沉淀以引入微粒。

10. 发明授权

US5712269A M.sub.2 receptor ligand for the treatment of neurological disorders 失效
标题翻译： M2受体配体用于治疗神经系统疾病
公开(公告)号：US5712269A
公开(公告)日：1998-01-27
申请号：US377667
申请日：1995-01-24
申请人： R. Tyler McCabe , Bryan R. Wilson , Christopher A. Rhodes
发明人： R. Tyler McCabe , Bryan R. Wilson , Christopher A. Rhodes
IPC分类号： A61K31/55 , A61P25/28 , C07D471/04
CPC分类号： C07D471/04 , A61K31/55
摘要： Muscarinic M.sub.2 receptor ligands are described which are suitable for the treatment of neurological disorders, and which may be administered with minimal side-effects. A method of synthesis of these compounds is also described.
摘要翻译：描述了适用于治疗神经障碍的毒蕈碱M2受体配体，其可以以最小的副作用施用。还描述了这些化合物的合成方法。

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