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1. 发明授权

US09370589B2 Switching fluorescent nanoparticle probe and fluorescent particle imaging method using same 有权
标题翻译：开关荧光纳米粒子探针和荧光颗粒成像方法使用相同
公开(公告)号：US09370589B2
公开(公告)日：2016-06-21
申请号：US13818392
申请日：2011-08-08
申请人： Isao Hara , Eiichi Ozeki , Hideo Saji , Shunsaku Kimura , Masahiro Ono , Takashi Temma
发明人： Isao Hara , Eiichi Ozeki , Hideo Saji , Shunsaku Kimura , Masahiro Ono , Takashi Temma
IPC分类号： A61K9/14 , A61K49/00
CPC分类号： A61K49/0089 , A61K49/0032 , A61K49/0093 , Y10S977/773 , Y10S977/927
摘要： The present invention provides a novel fluorescent nanoparticle imaging probe having a switching function (a function to quench a fluorescent dye during nanoparticle preparation, and emit fluorescence during imaging). A switching fluorescent nanoparticle probe comprising: a molecular assembly composed of an amphiphilic block polymer having a hydrophilic block chain and a hydrophobic block chain; and a fluorescent dye encapsulated in the molecular assembly, wherein (a) the hydrophilic block chain comprises, as an essential hydrophilic structural unit, a unit selected from a sarcosine unit and an alkylene oxide unit, (b) the hydrophobic block chain comprises, as an essential hydrophobic structural unit, a unit selected from the group consisting of an amino acid unit and a hydroxylic acid unit, and (c) the fluorescent dye is a cyanine compound represented by the formula (I): and two or more molecules of the fluorescent dye are encapsulated in the single molecular assembly.
摘要翻译：本发明提供了具有开关功能（在纳米颗粒制备期间淬灭荧光染料并在成像期间发射荧光的功能）的新型荧光纳米颗粒成像探针。一种开关荧光纳米颗粒探针，包括：由具有亲水嵌段链和疏水性嵌段链的两亲嵌段聚合物组成的分子组合; 以及包封在分子组合中的荧光染料，其中（a）所述亲水性嵌段链包含作为必需亲水性结构单元的选自肌氨酸单元和烯化氧单元的单元，（b）所述疏水性嵌段链包含：必需的疏水结构单元，选自氨基酸单元和羟基酸单元的单元，和（c）荧光染料是由式（I）表示的花青化合物：和荧光染料被封装在单分子组装中。

2. 发明授权

US08642008B2 Molecular probe for imaging of pancreatic islets and use of the same 有权
标题翻译：胰岛成像用分子探针及其用途
公开(公告)号：US08642008B2
公开(公告)日：2014-02-04
申请号：US12872837
申请日：2010-08-31
申请人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Yu Ogawa , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
发明人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Yu Ogawa , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
IPC分类号： A61K51/08
CPC分类号： A61K51/088
摘要： To provide a molecular probe for imaging of pancreatic islets. A molecular probe for use in imaging of pancreatic islets is provided. The molecular probe includes any one of the following polypeptides: polypeptides represented by the following formulae (1), (5), and (9); and polypeptides having homology with the foregoing polypeptides: Z-DLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (1) Z-DLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2 (5) B-DLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2 (9) where X in the formulae (1) and (5) and B- in the formula (9) indicate that an amino group is labeled with a group represented by the formula (I) below having an aromatic ring, wherein A represents either an aromatic hydrocarbon group or an aromatic heterocyclic group, R1 represents a substituent that contains radioactive iodine, R2 represents either a hydrogen atom or a substituent different from that represented by R1, and R3 represents any one of a bond, a methylene group, and an oxymethylene group.
摘要翻译：为胰岛成像提供分子探针。提供了一种用于胰岛成像的分子探针。分子探针包括以下多肽之一：由下式（1），（5）和（9）表示的多肽。和与前述多肽具有同源性的多肽：Z-DLSXQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2（1）Z-DLSKQMEEEAVRLFIEWLXNGGPSSGAPPPS-NH2（5）B-DLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2（9）其中式（1）和（5）中的X和式（9）表示氨基用具有芳环的下式（I）表示的基团标记，其中A表示芳香族烃基或芳香族杂环基，R 1表示含有放射性碘的取代基， R2表示氢原子或与R1表示的不同的取代基，R3表示键，亚甲基和氧亚甲基中的任一个。

3. 发明申请

US20120029209A1 METHOD FOR SYNTHESIZING [18F]SFB USING MICROSYNTHESIS TECHNIQUE 审中-公开
标题翻译：使用微结构技术合成[18 F] SFB的方法
公开(公告)号：US20120029209A1
公开(公告)日：2012-02-02
申请号：US13254152
申请日：2010-03-01
申请人： Hiroaki Nakanishi , Hidekazu Saiki , Hideo Saji , Hiroyuki Kimura , Hidekazu Kawashima , Kenji Tomatsu , Yuji Kuge
发明人： Hiroaki Nakanishi , Hidekazu Saiki , Hideo Saji , Hiroyuki Kimura , Hidekazu Kawashima , Kenji Tomatsu , Yuji Kuge
IPC分类号： C07D207/46
CPC分类号： C07D207/404 , A61K51/00 , C07B59/001 , C07B59/002
摘要： A method for synthesizing [18F]SFB is disclosed, which comprises using a microreactor including a substrate having one channel formed therein so as to have a cross-sectional width of 1 mm or less and a cross-sectional depth of 1 mm or less, the channel being connected to a raw material injection port and a first reagent injection port at one end thereof, and connected to a second reagent injection port at a position far from the one end thereof, and connected to a third reagent injection port at a position far from the second reagent injection port in a direction toward another end thereof, and connected to a liquid discharge port at the other end thereof; and continuously performing a three-step reaction by allowing a reaction solution to flow through the channel serving as a reaction channel from the one end to the other end thereof without taking out the reaction solution from anywhere between the one end and the other end of the channel.
摘要翻译：公开了一种合成[18F] SFB的方法，其包括使用包括其中形成有一个通道的基板的微反应器，以使其横截面宽度为1mm以下，横截面深度为1mm以下，所述通道在其一端连接到原料注入口和第一试剂注入口，并且在远离其一端的位置处连接到第二试剂注入口，并且连接到位于其的一端的第三试剂注入口远离第二试剂注入口朝向其另一端的方向，并且在另一端连接到液体排出口; 并且通过使反应溶液从一端到另一端流过作为反应通道的通道而不从其一端到另一端的任何位置取出反应溶液，从而连续进行三步反应渠道。

4. 发明申请

US20110081663A1 Molecular Probe for Imaging of Pancreatic Islets and Use of the Same 有权
标题翻译：胰岛成像用分子探针及其用途
公开(公告)号：US20110081663A1
公开(公告)日：2011-04-07
申请号：US12893896
申请日：2010-09-29
申请人： Hideo Saji , Nobuya Inagaki , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
发明人： Hideo Saji , Nobuya Inagaki , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
IPC分类号： G01N33/53 , C07K14/00
CPC分类号： A61K51/08
摘要： A molecular probe for imaging of pancreatic islets is provided. The molecular probe includes a polypeptide represented by the following formula (1), or a polypeptide that has a homology with the foregoing polypeptide. (SEQ ID NO. 1) Z-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSX-NH2 (1) Wherein “X” represents a lysine residue, an amino group of a side chain of the lysine residue being labeled with a group represented by the following chemical formula (I), wherein A represents an aromatic hydrocarbon group or an aromatic heterocyclic group; R1 represents a substituent that contains 11C, 13N, 15O, 18F, 64Cu, 67Ga, 68Ga, 75Br, 76Br, 77Br, 99mTc, 111In, 123I, 124I, 125I, or 131I; R2 represents either a hydrogen atom, or a substituent different from that represented by R1; and R3 represents any one of a bond, an alkylene group having 1 to 6 carbon atoms, and an oxyalkylene group having 1 to 6 carbon atoms.
摘要翻译：提供了用于胰岛成像的分子探针。分子探针包括由下式（1）表示的多肽，或与前述多肽具有同源性的多肽。（SEQ ID NO.1）Z-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPSX-NH2（1）其中，“X”表示赖氨酸残基，赖氨酸残基的侧链的氨基用下述化学式（I）表示的基团标记，其中A表示芳族烃基或芳族杂环基; R1表示含有11C，13N，150C，18F，64Cu，67Ga，68Ga，75Br，76Br，77Br，99mTc，111In，123I，124I，125I或131I的取代基; R2表示氢原子或与R1表示的取代基不同的取代基; R3表示碳原子数1〜6的亚烷基，碳原子数1〜6的氧亚烷基。

5. 发明申请

US20110033381A1 MOLECULAR PROBE FOR IMAGING OF PANCREATIC ISLET AND THE PRECURSOR, AND USE OF THE SAME 审中-公开
标题翻译：用于成像胰腺和前列腺的分子探针及其用途
公开(公告)号：US20110033381A1
公开(公告)日：2011-02-10
申请号：US12854007
申请日：2010-08-10
申请人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Yu Ogawa , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
发明人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Yu Ogawa , Konomu Hirao , Kenji Nagakawa , Hirokazu Matsuda
IPC分类号： A61K51/08 , C07K14/00 , A61K49/00
CPC分类号： A61K51/08 , C07K14/435 , C07K14/57563 , Y02P20/55
摘要： A precursor of molecular probe for imaging of pancreatic islets is provided. A polypeptide represented by any one of the following formulae (1) to (4), or a polypeptide having a homology with the foregoing polypeptide. *-DLSK* QMEEEAVRLFIEWLK* NGGPSSGAPPPSK-NH2(1) *-LSK* QMEEEAVRLFIEWLK* NGGPSSGAPPPSK-NH2(2) *-SK* QMEEEAVRLFIEWLK* NGGPSSGAPPPSK-NH2(3) *-K* QMEEEAVRLFIEWLK* NGGPSSGAPPPSK-NH2,(4) wherein *- indicates that an α-amino group at an N-terminus is protected by a protecting group or modified with a modifying group having no electric charge; K* indicates that an amino group of a side chain of a lysine is protected by a protecting group; and —NH2 indicates that a carboxyl group at a C-terminus is amidated.
摘要翻译：提供了用于胰岛成像的分子探针的前体。由下式（1）至（4）中任一项表示的多肽或与前述多肽具有同源性的多肽。 * -DLSK * QMEEEAVRLFIEWLK * NGGPSSGAPPPSK-NH2（1）* -LSK * QMEEEAVRLFIEWLK * NGGPSSGAPPPSK-NH2（2）* -SK * QMEEEAVRLFIEWLK * NGGPSSGAPPPSK-NH2（3）* -K * QMEEEAVRLFIEWLK * NGGPSSGAPPPSK-NH2，（4）其中 *表示N-末端的α-氨基被保护基保护或用不带电的修饰基团修饰; K *表示赖氨酸的侧链的氨基被保护基保护; 并且-NH 2表示C末端的羧基被酰胺化。

6. 发明授权

US07326403B2 Radioactive iodine-labeled compound 失效
标题翻译：放射性碘标记化合物
公开(公告)号：US07326403B2
公开(公告)日：2008-02-05
申请号：US11137479
申请日：2005-05-26
申请人： Yasuhiro Magata , Hideo Saji
发明人： Yasuhiro Magata , Hideo Saji
IPC分类号： A61K51/00 , A61M36/14 , C07D417/00
CPC分类号： C07D417/14 , A61K51/0455
摘要： A radioactive iodine-labeled compound represented by the following formula (I): wherein X represents a radioactive iodine atom which may substitute at an arbitrary position on the benzene ring (preferably 123I, 125I and the like.), n represents an integer of 1 to 3, R1 and R2 each independently represent a substituted or unsubstituted alkyl group, Y represents an alkylene group having 1 to 6 carbon atoms (preferably methylene group), M represents a counter ion, and m represents the number of ions required to neutralize the charge of the molecule. A radioactive iodine-labeled compound that can selectively accumulate in tumor cells or tumor tissue and a scintillation imaging agent containing the compound are provided.
摘要翻译：由下式（I）表示的放射性碘标记化合物：其中X表示可以在苯环上的任意位置取代的放射性碘原子（优选<123> I等），n表示1〜3的整数，R 1和R 2各自独立地表示取代或未取代的烷基，Y表示具有1至6个碳原子的亚烷基（优选亚甲基），M表示抗衡离子，m表示中和分子的电荷所需的离子数。提供可以选择性地积聚在肿瘤细胞或肿瘤组织中的放射性碘标记的化合物和含有该化合物的闪烁显像剂。

7. 发明授权

US09849197B2 Switching-type fluorescent nanoparticle probe, and fluorescent molecular imaging method using same 有权
公开(公告)号：US09849197B2
公开(公告)日：2017-12-26
申请号：US14002327
申请日：2012-03-01
申请人： Hideo Saji , Shunsaku Kimura , Masahiro Ono , Takashi Temma , Isao Hara , Eiichi Ozeki
发明人： Hideo Saji , Shunsaku Kimura , Masahiro Ono , Takashi Temma , Isao Hara , Eiichi Ozeki
IPC分类号： A61K9/00 , A61K49/00
CPC分类号： A61K49/0054 , A61K49/0032 , A61K49/0034 , A61K49/0069 , A61K49/0093
摘要： [Problem] To provide a novel fluorescent nanoparticle imaging probe having a switching function (a function to quench a fluorescent dye in a blood component and emit fluorescence in a tumor or an inflamed site to be imaged).[Solution] A fluorescent nanoparticle probe comprising: a molecular assembly composed of an amphiphilic block polymer having a hydrophilic block chain and a hydrophobic block chain; and a fluorescent dye encapsulated in the assembly, wherein (a) the hydrophilic block chain comprises, as an essential hydrophilic structural unit, a unit selected from a sarcosine unit and an alkylene oxide unit, (b) the hydrophobic block chain comprises, as an essential hydrophobic structural unit, a unit selected from the group consisting of an amino acid unit and a hydroxylic acid unit, and (c) the fluorescent dye is a polylactic acid-bound cyanine compound comprising: a fluorescent group represented by the formula (I): and a polylactic acid group having 5 to 50 lactic acid units, and two or more molecules of the fluorescent dye are encapsulated in the single molecular assembly.

8. 发明授权

US08476449B2 Radioactive iodine labeled organic compound or salt thereof 失效
标题翻译：放射性碘标记的有机化合物或其盐
公开(公告)号：US08476449B2
公开(公告)日：2013-07-02
申请号：US13582047
申请日：2011-02-24
申请人： Hideo Saji , Masahiro Ono , Ikuya Seki
发明人： Hideo Saji , Masahiro Ono , Ikuya Seki
IPC分类号： C07D405/06 , C07D405/14 , C07D417/06 , C07D417/14 , C07F7/22
CPC分类号： C07D417/06 , A61K51/0453 , C07D405/06 , C07D405/14
摘要： The present invention is a compound represented by the following formula (1) or a salt thereof. Furthermore, the present invention is an imaging agent used for imaging a tau protein, the imaging agent containing a compound represented by the formula (1) below or a salt thereof. In the formula (1), R3 is a radioactive iodine.
摘要翻译：本发明是由下式（1）表示的化合物或其盐。此外，本发明是用于成像tau蛋白的成像剂，该成像剂含有下述式（1）表示的化合物或其盐。在式（1）中，R 3是放射性碘。

9. 发明申请

US20130052132A1 Method for Producing Radioactively Labeled Polypeptide 审中-公开
标题翻译：生产放射性标记多肽的方法
公开(公告)号：US20130052132A1
公开(公告)日：2013-02-28
申请号：US13369903
申请日：2012-02-09
申请人： Hideo Saji , Nobuya Inagaki , Hiroyuki Kimura , Kentaro Toyoda , Konomu Hirao , Hirokazu Matsuda
发明人： Hideo Saji , Nobuya Inagaki , Hiroyuki Kimura , Kentaro Toyoda , Konomu Hirao , Hirokazu Matsuda
IPC分类号： C07K14/00 , A61K51/08
CPC分类号： C07K14/57563 , A61K51/088 , C07K1/13
摘要： The present invention relates to a method for producing a polypeptide. The method includes labeling a molecular probe precursor represented by an amino acid sequence of the formula (1) using a labeling compound capable of labeling a lysine or lysine derivative: (1) Y1-Leu-Ser-Xaa12-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg- Leu-Phe-Ile-Glu-Trp-Leu-Xaa27-Asn-Gly-Y2 where Y1 represents an amino acid sequence represented by the formula (2) or the amino acid sequence represented by the formula (2) with 1 to 8 amino acids from the N-terminus being deleted, Xaa12 represents a lysine or lysine derivative, Xaa27 represents a basic amino acid having no functional group at its side chain that reacts with the labeling compound or represents methyl lysine or acetylated lysine, and Y2 represents an amino acid sequence represented by the formula (3) or the amino acid sequence represented by the formula (3) with 1 to 9 amino acids from the C-terminus being deleted: (2) His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp (3) Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser
摘要翻译：本发明涉及一种生产多肽的方法。该方法包括使用能够标记赖氨酸或赖氨酸衍生物的标记化合物来标记由式（1）的氨基酸序列表示的分子探针前体：（1）Y1-Leu-Ser-Xaa12-Gln-Met-Glu- Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Xaa27-Asn-Gly-Y2，其中Y1表示由式（2）表示的氨基酸序列或由缺失N末端1〜8个氨基酸的式（2），Xaa12表示赖氨酸或赖氨酸衍生物，Xaa27表示其侧链上没有与标记化合物反应的官能团的碱性氨基酸，赖氨酸或乙酰化赖氨酸，Y2表示由式（3）表示的氨基酸序列或由式（3）表示的氨基酸序列，其中C末端具有1至9个氨基酸缺失：（2）His- Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp（3）Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro

10. 发明申请

US20120107239A1 Precursor of Molecular Probe for Pancreatic Islet Imaging and Use of the Same 审中-公开
标题翻译：胰岛成像分析探针前体及其应用
公开(公告)号：US20120107239A1
公开(公告)日：2012-05-03
申请号：US13148303
申请日：2010-03-16
申请人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa
发明人： Nobuya Inagaki , Hideo Saji , Kentaro Toyoda , Hiroyuki Kimura , Konomu Hirao , Kenji Nagakawa
IPC分类号： A61K51/04 , C07D209/44
CPC分类号： A61K51/0446
摘要： A precursor of a molecular probe for imaging of pancreatic islets is a compound expressed as the following formula (I): wherein -V-X represents a substituent on a benzene ring, V represents a bond, R1, of OR1, R1 represents a C1-C6 alkylene group, R2 represents H (hydrogen atom), a C1-C6 alkyl group, a C7-C10 aralkyl group, or a protecting group, X represents a OMs group, a OTs group, a OTf group, Br (bromine atom), or I (iodine atom), and carbon marked with * is an asymmetric carbon atom.
摘要翻译：用于胰岛成像的分子探针的前体是以下式（I）表示的化合物：其中-VX表示苯环上的取代基，V表示OR1的键，R1表示C1-C6 亚烷基，R2表示H（氢原子），C1-C6烷基，C7-C10芳烷基或保护基，X表示OMs基，OTs基，OTf基，Br（溴原子）或I（碘原子），标有*的碳是不对称碳原子。

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