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1. 发明授权

US5939534A Factors mutated in the D1 cap region 失效
标题翻译： D1帽区域突变的因素
公开(公告)号：US5939534A
公开(公告)日：1999-08-17
申请号：US669284
申请日：1996-06-28
申请人： Makoto Inoue , Kaoru Kikuchi , Yoko Ishige , Akira Ito , Toru Kimura , Chikao Nakayama , Hiroshi Noguchi
发明人： Makoto Inoue , Kaoru Kikuchi , Yoko Ishige , Akira Ito , Toru Kimura , Chikao Nakayama , Hiroshi Noguchi
IPC分类号： C07K14/475 , C12N15/18 , C07K14/52 , C07K14/535
CPC分类号： C07K14/475
摘要： Human ciliary neurotrophic factor (human CNTF) mutants, in which at least the amino acid residue corresponding to position 153 of wild type human CNTF has been substituted with another amino acid residue in the amino acid sequence encoding human CNTF, exhibit an activity comparable or superior to that of wild type human CNTF. It is therefore expected that the human CNTF mutants would be effective as drugs with improved side effects such as reduction in appearance of an autoantibody, loss of body weight, anorexia, a dry cough, fatigue, etc.In cytokines having sequence similarity to human CNTF and abundant .alpha. helices (GH, PRL, EPO, G- CSF, LIF, IL-6, IL-2, IL-4, GM-CSF), there are further provided mutants in the D1 cap region.
摘要翻译： PCT No.PCT / JP94 / 02269 Sec。 371日期：1996年6月28日 102（e）日期1996年6月28日PCT 1994年12月27日PCT PCT。 WO95 / 18150 PCT公开号日期1995年7月6日人类睫状神经营养因子（人CNTF）突变体，其中至少对应于野生型人CNTF的位置153的氨基酸残基已被编码人CNTF的氨基酸序列中的另一个氨基酸残基取代，与野生型人CNTF相当或优于其活性的活性。因此，预期人CNTF突变体作为具有改善的副作用的药物是有效的，例如自身抗体的外观减少，体重减轻，厌食，干咳，疲劳等。在与人CNTF具有序列相似性的细胞因子中和丰富的α螺旋（GH，PRL，EPO，G-CSF，LIF，IL-6，IL-2，IL-4，GM-CSF），还在D1帽区域提供突变体。

2. 发明授权

US06391312B1 Remedies for diabetes 失效
标题翻译：糖尿病补救
公开(公告)号：US06391312B1
公开(公告)日：2002-05-21
申请号：US09355098
申请日：1999-07-23
申请人： Michiko Kishino , Chikao Nakayama , Mutsuo Taiji , Junji Ichihara , Hiroshi Noguchi
发明人： Michiko Kishino , Chikao Nakayama , Mutsuo Taiji , Junji Ichihara , Hiroshi Noguchi
IPC分类号： A61K3900
CPC分类号： A61K38/185
摘要： The present invention provides a therapeutic agent for treatment of diabetes and hyperlipemia, especially a therapeutic agent for treatment of type II diabetes mellitus, which comprises as the active ingredient a neurotrophic factor such as BDNF (brain-derived neurotrophic factor), ligands of trkB or trkC receptors, NGF, NT-3, NT-4/5, CNTF, GDNF, HGF, etc. Different from conventional oral hypoglycemic agents being mainly used in the treatment of type II diabetes mellitus, the agent of the present invention exhibit blood lipid regulating effects and body fat accumulation regulating effects, in addition to the blood glucose regulating effects. Thus, the agent of the present invention are novel, and can reduce the risk factors in diabetes accompanied by hyperlipemia or obesity, without using any other agent.
摘要翻译：本发明提供了用于治疗糖尿病和高脂血症的治疗剂，特别是用于治疗II型糖尿病的治疗剂，其包括作为活性成分的神经营养因子如BDNF（脑源性神经营养因子），trkB的配体或 trkC受体，NGF，NT-3，NT-4/5，CNTF，GDNF，HGF等。与常规口服降糖药不同，主要用于治疗II型糖尿病，本发明的药物显示血脂调节作用和体内脂肪蓄积调节作用，除血糖调节作用外。因此，本发明的药剂是新颖的，并且可以在不使用任何其它药剂的情况下降低伴有高脂血症或肥胖症的糖尿病的危险因素。

3. 发明授权

US06800607B2 Modified BDNF 失效
标题翻译：改性BDNF
公开(公告)号：US06800607B2
公开(公告)日：2004-10-05
申请号：US10220315
申请日：2002-08-29
申请人： Rie Igarashi , Yutaka Mizushima , Mutsuo Taiji , Chikao Nakayama , Hiroshi Noguchi
发明人： Rie Igarashi , Yutaka Mizushima , Mutsuo Taiji , Chikao Nakayama , Hiroshi Noguchi
IPC分类号： A61K3816
CPC分类号： C07K14/475 , A61K38/00
摘要： Modified BDNF having improved pharmacological activities, pharmacokinetics and physical properties can be obtained by modifying BDNF with a 1-acyl-glycerol derivative. This BDNF being modified with a 1-acyl-glycerol derivative of the present invention has more efficacious and more excellent pharmacokinetic properties with retaining the useful effects being characteristic to BDNF which are useful as remedies for neurodegenerative diseases and diabetes mellitus, and hence, it is particularly useful as a therapeutic agent for treatment of type 2 diabetes mellitus.
摘要翻译：通过用1-酰基 - 甘油衍生物改性BDNF可以获得具有改善的药理活性，药代动力学和物理性能的改性BDNF。用本发明的1-酰基 - 甘油衍生物修饰的BDNF具有更有效和更优异的药代动力学性质，保留了BDNF特有的有效作用，可作为神经变性疾病和糖尿病的治疗方法，因此，特别可用作治疗2型糖尿病的治疗剂。

4. 发明授权

US06472366B2 Hepatocyte growth factor for treatment of diabetes 失效
标题翻译：肝细胞生长因子治疗糖尿病
公开(公告)号：US06472366B2
公开(公告)日：2002-10-29
申请号：US10055380
申请日：2002-01-25
申请人： Michiko Kishino , Chikao Nakayama , Mutsuo Taiji , Junji Ichihara , Hiroshi Noguchi
发明人： Michiko Kishino , Chikao Nakayama , Mutsuo Taiji , Junji Ichihara , Hiroshi Noguchi
IPC分类号： A61K3900
CPC分类号： A61K38/185
摘要： The present invention provides a therapeutic agent for treatment of diabetes and hyperlipemia, especially a therapeutic agent for treatment of type II diabetes mellitus, which comprises as the active ingredient a neurotrophic factor such as BDNF (brain-derived neurotrophic factor), ligands of trkB or trkC receptors, NGF, NT-3, NT-4/5, CNTF, GDNF, HGF, etc. Different from conventional oral hypoglycemic agents being mainly used in the treatment of type II diabetes mellitus, the agent of the present invention exhibit blood lipid regulating effects and body fat accumulation regulating effects, in addition to the blood glucose regulating effects. Thus, the agent of the present invention are novel, and can reduce the risk factors in diabetes accompanied by hyperlipemia or obesity, without using any other agent.
摘要翻译：本发明提供了用于治疗糖尿病和高脂血症的治疗剂，特别是用于治疗II型糖尿病的治疗剂，其包括作为活性成分的神经营养因子如BDNF（脑源性神经营养因子），trkB的配体或 trkC受体，NGF，NT-3，NT-4/5，CNTF，GDNF，HGF等。与常规口服降糖药不同，主要用于治疗II型糖尿病，本发明的药物显示血脂调节作用和体内脂肪蓄积调节作用，除血糖调节作用外。因此，本发明的药剂是新颖的，并且可以在不使用任何其它药剂的情况下降低伴有高脂血症或肥胖症的糖尿病的危险因素。

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