公开(公告)号：US08765669B2

公开(公告)日：2014-07-01

申请号：US12999654

申请日：2009-06-15

申请人： Yasuhiro Kajihara ,  Takashi Tsuji ,  Izumi Sakamoto ,  Yuri Nambu ,  Naohiro Hayashi ,  Kazuyuki Ishii ,  Kazuhiro Fukae ,  Katsunari Tezuka ,  Hiroaki Asai

发明人： Yasuhiro Kajihara ,  Takashi Tsuji ,  Izumi Sakamoto ,  Yuri Nambu ,  Naohiro Hayashi ,  Kazuyuki Ishii ,  Kazuhiro Fukae ,  Katsunari Tezuka ,  Hiroaki Asai

IPC分类号： A61K38/26 ,  A61P3/10 ,  A61P7/12 ,  C07K14/605 ,  C07K1/00 ,  C07K14/00 ,  C07K17/00

CPC分类号： C07K14/605 ,  A61K38/00

摘要： Oligosaccharide chain added GLP-1 peptides are more stable in blood and more active in controlling blood-sugar levels than GLP-1 peptides without added oligosaccharides. Oligosaccharide chain added GLP-1 peptides having GLP-1 activity include at least one or at least two amino acids each substituted with an oligosaccharide chain added amino acid in GLP-1; a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or a GLP-1 analog. Oligosaccharide chain added GLP-1 peptides with at least one amino acid substituted with an oligosaccharide chain added amino acid include an oligosaccharide chain with oligo hyaluronic acid. Oligosaccharide chain added amino acids include oligosaccharide chains attached to amino acids via linkers.

摘要翻译： 添加糖链的GLP-1肽在血液中更稳定，并且在没有添加低聚糖的情况下比GLP-1肽更有效地控制血糖水平。 具有GLP-1活性的添加糖链的GLP-1肽包括GLP-1中由糖链连接的氨基酸取代的至少一个或至少两个氨基酸; 具有GLP-1的氨基酸序列的肽，其具有缺失，取代或添加一个或几个氨基酸; 或GLP-1类似物。 具有至少一个被寡糖链添加的氨基酸取代的氨基酸的添加糖链的GLP-1肽包括具有寡聚透明质酸的寡糖链。 寡糖链添加的氨基酸包括通过接头连接到氨基酸的寡糖链。

公开(公告)号：US20110195897A1

公开(公告)日：2011-08-11

申请号：US12999654

申请日：2009-06-15

申请人： Yasuhiro Kajihara ,  Takashi Tsuji ,  Izumi Sakamoto ,  Yuri Nambu ,  Naohiro Hayashi ,  Kazuyuki Ishii ,  Kazuhiro Fukae ,  Katsunari Tezuka ,  Hiroaki Asai

发明人： Yasuhiro Kajihara ,  Takashi Tsuji ,  Izumi Sakamoto ,  Yuri Nambu ,  Naohiro Hayashi ,  Kazuyuki Ishii ,  Kazuhiro Fukae ,  Katsunari Tezuka ,  Hiroaki Asai

IPC分类号： A61K38/26 ,  C07K14/605 ,  A61P3/10

CPC分类号： C07K14/605 ,  A61K38/00

摘要： Oligosaccharide chain added GLP-1 peptides are more stable in blood and more active in controlling blood-sugar levels than GLP-1 peptides without added oligosaccharides. Oligosaccharide chain added GLP-1 peptides having GLP-1 activity include at least one or at least two amino acids each substituted with an oligosaccharide chain added amino acid in GLP-1; a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or a GLP-1 analog. Oligosaccharide chain added GLP-1 peptides with at least one amino acid substituted with an oligosaccharide chain added amino acid include an oligosaccharide chain with oligo hyaluronic acid. Oligosaccharide chain added amino acids include oligosaccharide chains attached to amino acids via linkers.

摘要翻译： 添加糖链的GLP-1肽在血液中更稳定，并且在没有添加低聚糖的情况下比GLP-1肽更有效地控制血糖水平。 具有GLP-1活性的添加糖链的GLP-1肽包括GLP-1中由糖链连接的氨基酸取代的至少一个或至少两个氨基酸; 具有GLP-1的氨基酸序列的肽，其具有缺失，取代或添加一个或几个氨基酸; 或GLP-1类似物。 具有至少一个被寡糖链添加的氨基酸取代的氨基酸的添加糖链的GLP-1肽包括具有寡聚透明质酸的寡糖链。 寡糖链添加的氨基酸包括通过接头连接到氨基酸的寡糖链。

公开(公告)号：US08507429B2

公开(公告)日：2013-08-13

申请号：US13152082

申请日：2011-06-02

申请人： Yasuhiro Kajihara ,  Takashi Tsuji ,  Izumi Sakamoto ,  Yuri Nambu ,  Kazuhiro Fukae ,  Katsunari Tezuka ,  Hiroaki Asai

发明人： Yasuhiro Kajihara ,  Takashi Tsuji ,  Izumi Sakamoto ,  Yuri Nambu ,  Kazuhiro Fukae ,  Katsunari Tezuka ,  Hiroaki Asai

IPC分类号： A61K38/26 ,  A61K38/14

CPC分类号： C07K14/605 ,  A61K38/00

摘要： The present invention relates to an oligosaccharide chain added GLP-1 peptide that has higher stability in blood than that of GLP-1 and, preferably, exhibits higher activity of controlling blood-sugar levels than that of GLP-1. The present invention relates to an oligosaccharide chain added GLP-1 peptide having GLP-1 activity, wherein at least one amino acid is substituted with an oligosaccharide chain added amino acid, in: (a) GLP-1; (b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or (c) a GLP-1 analog.

摘要翻译： 本发明涉及一种与GLP-1相比血液中稳定性更高的糖链附加GLP-1肽，优选表现出比GLP-1更高的控制血糖水平的活性。 本发明涉及：（a）GLP-1;具有GLP-1活性的附加了糖链的GLP-1肽，其中至少一个氨基酸被添加了糖链的氨基酸取代。 （b）具有缺失，取代或添加一个或几个氨基酸的具有GLP-1氨基酸序列的肽; 或（c）GLP-1类似物。

公开(公告)号：US07985731B2

公开(公告)日：2011-07-26

申请号：US12140866

申请日：2008-06-17

申请人： Yasuhiro Kajihara ,  Takashi Tsuji ,  Izumi Sakamoto ,  Yuri Nambu ,  Kazuhiro Fukae ,  Katsunari Tezuka ,  Hiroaki Asai

发明人： Yasuhiro Kajihara ,  Takashi Tsuji ,  Izumi Sakamoto ,  Yuri Nambu ,  Kazuhiro Fukae ,  Katsunari Tezuka ,  Hiroaki Asai

IPC分类号： A61K38/26 ,  A61K38/14

CPC分类号： C07K14/605 ,  A61K38/00

摘要： The present invention relates to an oligosaccharide chain added GLP-1 peptide that has higher stability in blood than that of GLP-1 and, preferably, exhibits higher activity of controlling blood-sugar levels than that of GLP-1. The present invention relates to an oligosaccharide chain added GLP-1 peptide having GLP-1 activity, wherein at least one amino acid is substituted with an oligosaccharide chain added amino acid, in: (a) GLP-1; (b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or (c) a GLP-1 analog.

摘要翻译： 本发明涉及一种与GLP-1相比血液中稳定性更高的糖链附加GLP-1肽，优选表现出比GLP-1更高的控制血糖水平的活性。 本发明涉及：（a）GLP-1;具有GLP-1活性的附加了糖链的GLP-1肽，其中至少一个氨基酸被添加了糖链的氨基酸取代。 （b）具有缺失，取代或添加一个或几个氨基酸的具有GLP-1氨基酸序列的肽; 或（c）GLP-1类似物。

公开(公告)号：US20090111739A1

公开(公告)日：2009-04-30

申请号：US12140866

申请日：2008-06-17

申请人： Yasuhiro Kajihara ,  Takashi Tsuji ,  Izumi Sakamoto ,  Yuri Nambu ,  Kazuhiro Fukae ,  Katsunari Tezuka ,  Hiroaki Asai

发明人： Yasuhiro Kajihara ,  Takashi Tsuji ,  Izumi Sakamoto ,  Yuri Nambu ,  Kazuhiro Fukae ,  Katsunari Tezuka ,  Hiroaki Asai

IPC分类号： A61K38/16 ,  C07K14/00

CPC分类号： C07K14/605 ,  A61K38/00

摘要： The present invention relates to an oligosaccharide chain added GLP-1 peptide that has higher stability in blood than that of GLP-1 and, preferably, exhibits higher activity of controlling blood-sugar levels than that of GLP-1. The present invention relates to an oligosaccharide chain added GLP-1 peptide having GLP-1 activity, wherein at least one amino acid is substituted with an oligosaccharide chain added amino acid, in: (a) GLP-1; (b) a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or (c) a GLP-1 analog.

摘要翻译： 本发明涉及一种与GLP-1相比血液中稳定性更高的糖链附加GLP-1肽，优选表现出比GLP-1更高的控制血糖水平的活性。 本发明涉及：（a）GLP-1;具有GLP-1活性的附加了糖链的GLP-1肽，其中至少一个氨基酸被添加了糖链的氨基酸取代。 （b）具有缺失，取代或添加一个或几个氨基酸的具有GLP-1氨基酸序列的肽; 或（c）GLP-1类似物。

公开(公告)号：US08809258B2

公开(公告)日：2014-08-19

申请号：US12671238

申请日：2008-07-30

申请人： Yasuhiro Kajihara ,  Izumi Sakamoto ,  Yuri Nambu ,  Kazuhiro Fukae ,  Hiroaki Asai

发明人： Yasuhiro Kajihara ,  Izumi Sakamoto ,  Yuri Nambu ,  Kazuhiro Fukae ,  Hiroaki Asai

IPC分类号： A61K38/00 ,  C07K1/04 ,  C07K14/00

CPC分类号： C07K1/1133 ,  C07K1/04 ,  C07K1/1077 ,  C07K5/1008 ,  C07K7/06 ,  C07K9/00 ,  C07K14/001 ,  C07K14/4727

摘要： The present invention provides a method for producing a peptide, characterized in that it comprises converting an —SH group of a peptide comprising an amino acid residue having the —SH group to an —OH group, wherein said method comprises the following steps (a) to (c): (a) allowing an —SH group in a peptide to react with a methylating agent to convert the —SH group to an -SMe group; (b) allowing the -SMe group obtained in the step (a) to react with a cyanizing agent to produce a reaction intermediate; and (c) converting the reaction intermediate obtained in the step (b) to a peptide comprising an amino acid residue having an —OH group under more basic conditions than the conditions in the step (b).

摘要翻译： 本发明提供一种生产肽的方法，其特征在于包括将包含具有-SH基团的氨基酸残基的肽的-SH基转化为-OH基团，其中所述方法包括以下步骤（a） 至（c）：（a）使肽中的-SH基团与甲基化剂反应以将-SH基团转化为-SMe基团; （b）使步骤（a）中得到的-SMe基与氰化剂反应生成反应中间体; 和（c）将步骤（b）中获得的反应中间体转化为比在步骤（b）中的条件更碱性的条件下包含具有-OH基团的氨基酸残基的肽。

公开(公告)号：US20110172392A1

公开(公告)日：2011-07-14

申请号：US12671238

申请日：2008-07-30

申请人： Yasuhiro Kajihara ,  Izumi Sakamoto ,  Yuri Nambu ,  Kazuhiro Fukae ,  Hiroaki Asai

发明人： Yasuhiro Kajihara ,  Izumi Sakamoto ,  Yuri Nambu ,  Kazuhiro Fukae ,  Hiroaki Asai

IPC分类号： C07K1/113

CPC分类号： C07K1/1133 ,  C07K1/04 ,  C07K1/1077 ,  C07K5/1008 ,  C07K7/06 ,  C07K9/00 ,  C07K14/001 ,  C07K14/4727

摘要： The present invention provides a method for producing a peptide, characterized in that it comprises converting an —SH group of a peptide comprising an amino acid residue having the —SH group to an —OH group, wherein said method comprises the following steps (a) to (c): (a) allowing an —SH group in a peptide to react with a methylating agent to convert the —SH group to an —SMe group; (b) allowing the —SMe group obtained in the step (a) to react with a cyanizing agent to produce a reaction intermediate; and (c) converting the reaction intermediate obtained in the step (b) to a peptide comprising an amino acid residue having an —OH group under more basic conditions than the conditions in the step (b).

摘要翻译： 本发明提供一种生产肽的方法，其特征在于包括将包含具有-SH基团的氨基酸残基的肽的-SH基转化为-OH基团，其中所述方法包括以下步骤（a） 至（c）：（a）使肽中的-SH基团与甲基化剂反应以将-SH基团转化为-SMe基团; （b）使步骤（a）中得到的-SMe基与氰化剂反应生成反应中间体; 和（c）将步骤（b）中获得的反应中间体转化为比在步骤（b）中的条件更碱性的条件下包含具有-OH基团的氨基酸残基的肽。

公开(公告)号：US20120178905A1

公开(公告)日：2012-07-12

申请号：US13379832

申请日：2010-06-21

申请人： Yasuhiro Kajihara ,  Ryo Okamoto ,  Izumi Sakamoto ,  Kazuyuki Ishii

发明人： Yasuhiro Kajihara ,  Ryo Okamoto ,  Izumi Sakamoto ,  Kazuyuki Ishii

IPC分类号： C07K1/113

CPC分类号： C07K1/1077 ,  C07K1/1072

摘要： A process for chemically converting a peptide chain into a peptide thioester includes, when a —C(═X)—R1 group is introduced to the thiol group of the cysteine residue and then the resulting peptide is reacted with a compound having a leaving group represented by the formula: —NH—C(═Y)NHR3 in an organic solvent, the —NH—C(═Y)NHR3 group binds via addition reaction to the carboxyl group of the N-terminal-side peptide bond of the cysteine residue, whereby the peptide bond is cleaved and the C-terminal-side peptide fragment is cut off. Further, when the resulting peptide chain having the —NH—C(═Y)NHR3 group is reacted with a thiol in a buffer solution, a thiol exchange reaction occurs, namely, the thiol group of the thiol binds to the carbonyl carbon to which the —NH—C(═Y)NHR3 group has bound, whereby the —NH—C(═Y)NHR3 group is eliminated.

摘要翻译： 将肽链化学转化为肽硫酯的方法包括当将-C（= X）-R1基团引入半胱氨酸残基的硫醇基团时，然后将所得肽与具有离去基团的化合物反应 通过-NH-C（= Y）NHR 3在有机溶剂中，-NH-C（= Y）NHR 3基团通过加成反应与半胱氨酸残基的N-末端侧肽键的羧基结合 ，由此肽键被切割并且C末端侧肽片段被切断。 此外，当所得的具有-NH-C（= Y）NHR 3基团的肽链与缓冲溶液中的硫醇反应时，发生巯基交换反应，即硫醇的硫醇基与羰基碳结合， -NH-C（= Y）NHR 3基团结合，从而消除-NH-C（= Y）NHR 3基团。

公开(公告)号：US08642725B2

公开(公告)日：2014-02-04

申请号：US13379832

申请日：2010-06-21

申请人： Yasuhiro Kajihara ,  Ryo Okamoto ,  Izumi Sakamoto ,  Kazuyuki Ishii

发明人： Yasuhiro Kajihara ,  Ryo Okamoto ,  Izumi Sakamoto ,  Kazuyuki Ishii

IPC分类号： A61K38/00 ,  C07K2/00 ,  C07K4/00 ,  C07K5/00 ,  C07K7/00 ,  C07K14/00 ,  C07K16/00 ,  C07K17/00

CPC分类号： C07K1/1077 ,  C07K1/1072

摘要： A process for chemically converting a peptide chain into a peptide thioester includes, when a —C(═X)—R1 group is introduced to the thiol group of the cysteine residue and then the resulting peptide is reacted with a compound having a leaving group represented by the formula: —NH—C(═Y)NHR3 in an organic solvent, the —NH—C(═Y)NHR3 group binds via addition reaction to the carboxyl group of the N-terminal-side peptide bond of the cysteine residue, whereby the peptide bond is cleaved and the C-terminal-side peptide fragment is cut off. Further, when the resulting peptide chain having the —NH—C(═Y)NHR3 group is reacted with a thiol in a buffer solution, a thiol exchange reaction occurs, namely, the thiol group of the thiol binds to the carbonyl carbon to which the —NH—C(═Y)NHR3 group has bound, whereby the —NH—C(═Y)NHR3 group is eliminated.

摘要翻译： 将肽链化学转化为肽硫酯的方法包括当将-C（= X）-R1基团引入半胱氨酸残基的硫醇基团时，然后将所得肽与具有离去基团的化合物反应 通过-NH-C（= Y）NHR 3在有机溶剂中，-NH-C（= Y）NHR 3基团通过加成反应与半胱氨酸残基的N-末端侧肽键的羧基结合 ，由此肽键被切割并且C末端侧肽片段被切断。 此外，当所得的具有-NH-C（= Y）NHR 3基团的肽链与缓冲溶液中的硫醇反应时，发生巯基交换反应，即硫醇的硫醇基与羰基碳结合， -NH-C（= Y）NHR 3基团结合，从而消除-NH-C（= Y）NHR 3基团。

公开(公告)号：US4655211A

公开(公告)日：1987-04-07

申请号：US763589

申请日：1985-08-08

申请人： Izumi Sakamoto ,  Tukasa Unigame ,  Kunihiko Takagi

发明人： Izumi Sakamoto ,  Tukasa Unigame ,  Kunihiko Takagi

IPC分类号： A61K38/16 ,  A61K9/14 ,  A61K9/16 ,  A61K9/70 ,  A61K38/00 ,  A61K38/17 ,  A61K38/46 ,  A61L24/00 ,  A61L26/00 ,  C12N9/10 ,  C12N9/64 ,  C12N9/74 ,  A61L15/00

CPC分类号： A61L24/0042 ,  A61K9/146 ,  A61K9/1658 ,  A61K9/70 ,  A61L26/009 ,  C12N9/1044 ,  C12N9/64 ,  C12N9/6429 ,  C12Y304/21005 ,  A61K38/00 ,  A61L2400/04

摘要： A hemostatic agent and method for preparation thereof are described, said hemostatic agent comprising a carrier in the shape of flake or fiber having thrombin and Factor XIII fixed thereto, wherein said carrier is composed of a biodegradable material having a water absorption capability of about 50 weight percent or more, said flake has a longer dimension of about 5000 microns or less, a shorter dimension of about 3000 microns or less, and a thickness of about 2000 microns or less, and said fiber has a single yarn fineness of about 30 deniers or less and a yarn length of about 10 mm or less.

摘要翻译： 描述了止血剂及其制备方法，所述止血剂包括具有凝血酶的片状或纤维形式的载体和固定有凝血酶的因子XIII，其中所述载体由吸水能力为约50重量％的可生物降解的材料 所述薄片具有约5000微米或更小的较长尺寸，约3000微米或更小的较短尺寸和约2000微米或更小的厚度，并且所述纤维的单丝细度为约30旦尼尔或 较短的纱线长度为约10mm以下。