公开(公告)号：US06861538B1

公开(公告)日：2005-03-01

申请号：US10070435

申请日：2000-09-20

申请人： Mikio Watanabe ,  Jiro Takano ,  Yoshimi Ishihara ,  Masahiro Murakami

发明人： Mikio Watanabe ,  Jiro Takano ,  Yoshimi Ishihara ,  Masahiro Murakami

IPC分类号： C07D319/12 ,  C07D323/00 ,  C07D321/00 ,  C07D323/04 ,  C08G63/00

CPC分类号： C07D319/12 ,  C07D323/00

摘要： The object of the present invention is to provide a novel method for effectively producing a cyclic lactic acid oligomer, and a cyclic lactic acid oligomer produced by the method. According to the present invention, there is provided a method for producing a cyclic lactic acid oligomer represented by the following formula (1): wherein m represents an integer of 1 to 30, wherein lactides are polymerized in the presence of an alkali metal compound represented by the following formula (2): R—Y—Me  (2) wherein R represents an aliphatic group, aromatic group, —Si(R10)(R11)(R12), —CH(R20) CONR21R22 or —CH(R30)COOR31, wherein each of R10, R11 and R12 independently represents an aliphatic or aromatic group, R20 represents an aliphatic group, each of R21 and R22 independently represents a hydrogen atom, aliphatic group or aromatic group, R30 represents an aliphatic group, and R31 represents a hydrogen atom, aliphatic group or aromatic group; Y represents —O—, —S— or —NR40—, wherein R40 represents a hydrogen atom, aliphatic group or aromatic group; and Me represents an alkali metal; and, a cyclic lactic acid oligomer produced by the above production method.

摘要翻译： 本发明的目的是提供一种有效制备环状乳酸低聚物的新方法和通过该方法制备的环状乳酸低聚物。 根据本发明，提供了一种由下式（1）表示的环状乳酸低聚物的制备方法：其中m表示1〜30的整数，其中丙交酯在表示的碱金属化合物的存在下聚合 通过下式（2）表示：其中R表示脂族基，芳基，-Si（R 10）（R 11）（R 12），-CH（R 20）CONR 21 R 22或-CH（R 30）COOR 31，其中R 10，R 11和R 12各自独立地表示脂族或芳族基团，R 20表示 脂族基团，R 21和R 22各自独立地表示氢原子，脂肪族基团或芳香族基团，R 30表示脂肪族基团，R 31表示氢原子，脂肪族基团或芳香族基团 ; Y表示-O - ， - S-或-NR 40 - ，其中R 40表示氢原子，脂族基团或芳族基团; andMe代表碱金属; 和通过上述制备方法制备的环状乳酸低聚物。

公开(公告)号：US07745688B2

公开(公告)日：2010-06-29

申请号：US11765730

申请日：2007-06-20

申请人： Takaomi Saido ,  Nobuhisa Iwata ,  Takashi Saito ,  Takahiro Suemoto ,  Jiro Takano

发明人： Takaomi Saido ,  Nobuhisa Iwata ,  Takashi Saito ,  Takahiro Suemoto ,  Jiro Takano

IPC分类号： A01K67/033 ,  G01N33/00

CPC分类号： C12N15/8509 ,  A01K67/0275 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2227/106 ,  A01K2267/0312

摘要： The present invention provides a non-human model mammal of Alzheimer's disease (AD) containing chimeric amyloid precursor protein (APP) gene capable of producing human amyloid β peptide (Aβ) or a living part thereof, characterized in that Aβ42/Aβ40 ratio at 8-weeks-old is about 7-fold or more (about 140-fold or more in homozygote) higher compared to that of a corresponding wild-type mammal. Moreover, the present invention provides the mammal or a living part thereof, further characterized in that the level of APP expression is not significantly different compared to the corresponding wild-type mammal, and a screening method for a prophylactic and/or therapeutic drug for AD, a biomarker in biological fluids and molecular imaging of amyloid deposition or other pathological changes in the brain for an early diagnosis of AD using the mammal or a living part thereof.

摘要翻译： 本发明提供了含有能够产生人淀粉样蛋白的嵌合淀粉样蛋白前体蛋白（APP）基因的非人模型的阿尔茨海默病（AD）哺乳动物。 肽（A＆bgr）或其活性部分，其特征在于8周龄的A / B比值与约7倍或更多（纯合子中约140倍或更多）相比较， 相应的野生型哺乳动物。 此外，本发明提供了哺乳动物或其生物体部分，其特征还在于，与相应的野生型哺乳动物相比，APP表达水平没有显着差异，以及用于AD的预防和/或治疗药物的筛选方法 生物流体中的生物标志物和淀粉样蛋白沉积的分子成像或脑中的其它病理变化，以便使用哺乳动物或其生物部分进行AD的早期诊断。

公开(公告)号：US20070294779A1

公开(公告)日：2007-12-20

申请号：US11765730

申请日：2007-06-20

申请人： Takaomi SAIDO ,  Nobuhisa IWATA ,  Takashi SAITO ,  Takahiro SUEMOTO ,  Jiro TAKANO

发明人： Takaomi SAIDO ,  Nobuhisa IWATA ,  Takashi SAITO ,  Takahiro SUEMOTO ,  Jiro TAKANO

IPC分类号： A01K67/027

CPC分类号： C12N15/8509 ,  A01K67/0275 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/05 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2227/106 ,  A01K2267/0312

摘要： The present invention provides a non-human model mammal of Alzheimer's disease (AD) containing chimeric amyloid precursor protein (APP) gene capable of producing human amyloid β peptide (Aβ) or a living part thereof, characterized in that Aβ42/Aβ40 ratio at 8-weeks-old is about 7-fold or more (about 140-fold or more in homozygote) higher compared to that of a corresponding wild-type mammal. Moreover, the present invention provides the mammal or a living part thereof, further characterized in that the level of APP expression is not significantly different compared to the corresponding wild-type mammal, and a screening method for a prophylactic and/or therapeutic drug for AD, a biomarker in biological fluids and molecular imaging of amyloid deposition or other pathological changes in the brain for an early diagnosis of AD using the mammal or a living part thereof.

摘要翻译： 本发明提供一种含有能够产生人淀粉样蛋白β肽（Abeta）或其生物部分的嵌合淀粉样蛋白前体蛋白（APP）基因的阿尔茨海默氏病（AD）的非人模型哺乳动物，其特征在于Abeta42 / Abeta40比率为8 与相应的野生型哺乳动物相比，每周约为7倍或更多（纯合子中约140倍或更多）。 此外，本发明提供了哺乳动物或其生物体部分，其特征还在于，与相应的野生型哺乳动物相比，APP表达水平没有显着差异，以及用于AD的预防和/或治疗药物的筛选方法 生物流体中的生物标志物和淀粉样蛋白沉积的分子成像或脑中的其它病理变化，以便使用哺乳动物或其生物部分进行AD的早期诊断。

公开(公告)号：US06825314B1

公开(公告)日：2004-11-30

申请号：US10070436

申请日：2002-06-25

申请人： Mikio Watanabe ,  Jiro Takano ,  Yoshimi Ishihara ,  Masahiro Murakami

发明人： Mikio Watanabe ,  Jiro Takano ,  Yoshimi Ishihara ,  Masahiro Murakami

IPC分类号： C08G6300

CPC分类号： C07D323/00

摘要： The object of the present invention is to provide a novel method for effectively producing a cyclic lactic acid oligomer, and a cyclic lactic acid oligomer produced by the method. According to the present invention, there is provided a method for producing a cyclic lactic acid oligomer represented by the following formula (1): wherein m represents an integer of 1 to 30, wherein lactides are polymerized in the presence of an alkali metal compound represented by the following formula (2): R—Y—Me  (2)  wherein R represents an aliphatic group, aromatic group, —Si(R10)(R11)(R12), —CH(R20)CONR21R22 or —CH(R30)COOR31, wherein each of R10, R11 and R12 independently represents an aliphatic or aromatic group, R20 represents an aliphatic group, each of R21 and R22 independently represents a hydrogen atom, aliphatic group or aromatic group, R30 represents an aliphatic group, and R31 represents a hydrogen atom, aliphatic group or aromatic group; Y represents —O—, —S— or —NR40—, wherein R40 represents a hydrogen atom, aliphatic group or aromatic group; and Me represents an alkali metal; and, a cyclic lactic acid oligomer produced by the above production method.

摘要翻译： 本发明的目的是提供一种有效制备环状乳酸低聚物的新方法和通过该方法制备的环状乳酸低聚物。 根据本发明，提供了一种由下式（1）表示的环状乳酸低聚物的制备方法：其中m表示1〜30的整数，其中丙交酯在表示的碱金属化合物的存在下聚合 通过下式（2）表示：其中R表示脂族基，芳基，-Si（R 10）（R 11）（R 12），-CH（R 20）CONR 21 R 22或-CH（R 30）COOR 31，其中R 10，R 11和R 12各自独立地表示脂族或芳族基团，R 20表示 脂族基团，R 21和R 22各自独立地表示氢原子，脂肪族基团或芳香族基团，R 30表示脂肪族基团，R 31表示氢原子，脂肪族基团或芳香族基团 ; Y表示-O - ， - S-或-NR 40 - ，其中R 40表示氢原子，脂族基团或芳族基团; andMe代表碱金属; 和通过上述制备方法制备的环状乳酸低聚物。