公开(公告)号：US08741339B2

公开(公告)日：2014-06-03

申请号：US12672496

申请日：2009-07-29

申请人： Yasuki Kato ,  Mitsunori Harada ,  Hiroyuki Saito ,  Tatsuyuki Hayashi

发明人： Yasuki Kato ,  Mitsunori Harada ,  Hiroyuki Saito ,  Tatsuyuki Hayashi

IPC分类号： A61K47/48 ,  A61K9/10

CPC分类号： B82Y5/00 ,  A61K47/60 ,  A61K47/642 ,  A61K47/644 ,  A61K47/6845 ,  A61K47/6849 ,  A61K47/6905 ,  A61K47/6907

摘要： The present invention provides an active targeting polymer micelle encapsulating a drug, preventing an inappropriate release of a drug which may damage a normal cell. A polymer micelle 100 includes a backbone polymer unit 10 that has a target binding site 11 and a backbone polymer unit 20 that has a drug 14 and is free from the target binding site 11, such polymer units 10 and 20 being disposed in a radial arrangement in a state where the target binding site 11 is directed outward and the drug 14 is directed inward, in which: i) when the micelle is bound to a target 40 while maintaining the radial arrangement, the micelle is taken up into a cell 50 supplying the target 40 through endocytosis, and the drug 14 is released into the cell 50 by collapse of the radial arrangement in the cell 50; and ii) when the radial arrangement collapses in blood 60 before the micelle is bound to a target 40, the unit 20 is excreted through metabolism, to thereby prevent a normal cell from being damaged by the drug 14.

摘要翻译： 本发明提供了包封药物的活性靶向聚合物胶束，防止可能损害正常细胞的药物的不适当释放。 聚合物胶束100包括具有靶结合位点11的骨架聚合物单元10和具有药物14并且不含靶结合位点11的主链聚合物单元20，这样的聚合物单元10和20以径向排列 在靶结合位点11向外指向并且向内指向药物14的状态下，其中：i）当保持径向布置时胶束被结合到靶40上时，胶束被吸收到电池50中 靶40通过内吞作用，并且药物14通过细胞50中的径向排列的折叠而释放到细胞50中; 和ii）当胶束与靶标40结合之前径向布置在血液60中塌陷时，单元20通过代谢排泄，从而防止正常细胞被药物14损伤。

公开(公告)号：US20140017192A1

公开(公告)日：2014-01-16

申请号：US14008181

申请日：2012-04-02

申请人： Hiroyuki Saito ,  Katsutoshi Kobayashi ,  Ryosuke Tanaka ,  Mitsunori Harada ,  Yasuki Kato

发明人： Hiroyuki Saito ,  Katsutoshi Kobayashi ,  Ryosuke Tanaka ,  Mitsunori Harada ,  Yasuki Kato

IPC分类号： A61K47/48 ,  A61K31/69

CPC分类号： A61K47/48207 ,  A61K31/69 ,  A61K47/60 ,  A61K47/645

摘要： A pharmaceutical composition includes a block copolymer having a hydrophilic segment, a hydrophobic segment, and a boronic acid compound bound to a side chain of the hydrophobic segment via a linker moiety that includes a heterocyclic structure. The heterocyclic structure contains a cyclic skeleton that includes a boron atom of the boronic acid compound, one or two atom(s) X bound to the boron atom and selected from an oxygen atom and a nitrogen atom, and one or two carbon atom(s) (respectively) bound to the atom(s) X. The block copolymer further includes at least one organic group bound to the carbon atom(s). The organic group(s) contain(s) an aromatic group or cyclic alkyl group that sterically protects a boronic acid ester bond and/or a boron amide bond resulting from bonding between the boron atom and the atom(s) X.

摘要翻译： 药物组合物包括具有亲水链段，疏水链段和通过包含杂环结构的连接体部分与疏水片段的侧链结合的硼酸化合物的嵌段共聚物。 杂环结构包含环状骨架，其包含硼酸化合物的硼原子，与硼原子结合并选自氧原子和氮原子的一个或两个原子X以及一个或两个碳原子 ）（分别）与X原子结合。嵌段共聚物还包括至少一个与碳原子键合的有机基团。 有机基团含有空间保护由硼原子和原子X之间的键合产生的硼酸酯键和/或硼酰胺键的芳族基团或环状烷基。

公开(公告)号：US09561284B2

公开(公告)日：2017-02-07

申请号：US14008181

申请日：2012-04-02

申请人： Hiroyuki Saito ,  Katsutoshi Kobayashi ,  Ryosuke Tanaka ,  Mitsunori Harada ,  Yasuki Kato

发明人： Hiroyuki Saito ,  Katsutoshi Kobayashi ,  Ryosuke Tanaka ,  Mitsunori Harada ,  Yasuki Kato

IPC分类号： A61K47/48 ,  A61K31/69

CPC分类号： A61K47/48207 ,  A61K31/69 ,  A61K47/60 ,  A61K47/645

摘要： A pharmaceutical composition includes a block copolymer having a hydrophilic segment, a hydrophobic segment, and a boronic acid compound bound to a side chain of the hydrophobic segment via a linker moiety that includes a heterocyclic structure. The heterocyclic structure contains a cyclic skeleton that includes a boron atom of the boronic acid compound, one or two atom(s) X bound to the boron atom and selected from an oxygen atom and a nitrogen atom, and one or two carbon atom(s) (respectively) bound to the atom(s) X. The block copolymer further includes at least one organic group bound to the carbon atom(s). The organic group(s) contain(s) an aromatic group or cyclic alkyl group that sterically protects a boronic acid ester bond and/or a boron amide bond resulting from bonding between the boron atom and the atom(s) X.

摘要翻译： 药物组合物包括具有亲水链段，疏水链段和通过包含杂环结构的连接体部分与疏水片段的侧链结合的硼酸化合物的嵌段共聚物。 杂环结构包含环状骨架，其包含硼酸化合物的硼原子，与硼原子结合并选自氧原子和氮原子的一个或两个原子X以及一个或两个碳原子 ）（分别）与X原子结合。嵌段共聚物还包括至少一个与碳原子键合的有机基团。 有机基团含有空间保护由硼原子和原子X之间的键合产生的硼酸酯键和/或硼酰胺键的芳族基团或环状烷基。

公开(公告)号：US20110136990A1

公开(公告)日：2011-06-09

申请号：US12993085

申请日：2009-05-20

申请人： Mitsunori Harada ,  Hiroyuki Saito ,  Yasuki Kato

发明人： Mitsunori Harada ,  Hiroyuki Saito ,  Yasuki Kato

IPC分类号： C08G63/00

CPC分类号： A61K9/0019 ,  A61K31/337 ,  A61K47/60 ,  A61K47/64 ,  C08G69/10 ,  C08G69/40

摘要： A method is provided for preparing a polymer derivative of docetaxel provided by an ester linkage between at least one hydroxyl group of docetaxel and a carboxyl group of an aspartic acid side chain of a block copolymer containing polyethylene glycol and polyaspartic acid, which method includes a step of adjusting the ratio and/or the number of docetaxel molecules linked to the block copolymer to thereby control the release rate of docetaxel from the resultant polymer derivative of docetaxel.

摘要翻译： 提供了一种制备多烯紫杉醇聚合物衍生物的方法，所述多烯紫杉醇由多烯紫杉醇的至少一个羟基与包含聚乙二醇和聚天冬氨酸的嵌段共聚物的天冬氨酸侧链的羧基之间的酯键提供，该方法包括步骤 调节与嵌段共聚物连接的多西紫杉醇分子的比例和/或数量，从而控制得自多西紫杉醇聚合物衍生物的多西他赛的释放速率。

公开(公告)号：US20100221320A1

公开(公告)日：2010-09-02

申请号：US12672496

申请日：2009-07-29

申请人： Yasuki Kato ,  Mitsunori Harada ,  Hiroyuki Saito ,  Tatsuyuki Hayashi

发明人： Yasuki Kato ,  Mitsunori Harada ,  Hiroyuki Saito ,  Tatsuyuki Hayashi

IPC分类号： A61K9/48

CPC分类号： B82Y5/00 ,  A61K47/60 ,  A61K47/642 ,  A61K47/644 ,  A61K47/6845 ,  A61K47/6849 ,  A61K47/6905 ,  A61K47/6907

摘要： The present invention provides an active targeting polymer micelle encapsulating a drug, preventing an inappropriate release of a drug which may damage a normal cell. A polymer micelle 100 includes a backbone polymer unit 10 that has a target binding site 11 and a backbone polymer unit 20 that has a drug 14 and is free from the target binding site 11, such polymer units 10 and 20 being disposed in a radial arrangement in a state where the target binding site 11 is directed outward and the drug 14 is directed inward, in which: i) when the micelle is bound to a target 40 while maintaining the radial arrangement, the micelle is taken up into a cell 50 supplying the target 40 through endocytosis, and the drug 14 is released into the cell 50 by collapse of the radial arrangement in the cell 50; and ii) when the radial arrangement collapses in blood 60 before the micelle is bound to a target 40, the unit 20 is excreted through metabolism, to thereby prevent a normal cell from being damaged by the drug 14.

摘要翻译： 本发明提供了包封药物的活性靶向聚合物胶束，防止可能损害正常细胞的药物的不适当释放。 聚合物胶束100包括具有靶结合位点11的骨架聚合物单元10和具有药物14并且不含靶结合位点11的主链聚合物单元20，这样的聚合物单元10和20以径向排列 在靶结合位点11向外指向并且向内指向药物14的状态下，其中：i）当保持径向布置时胶束被结合到靶40上时，胶束被吸收到电池50中 靶40通过内吞作用，并且药物14通过细胞50中的径向排列的折叠而释放到细胞50中; 和ii）当胶束与靶标40结合之前径向布置在血液60中塌陷时，单元20通过代谢排泄，从而防止正常细胞被药物14损伤。

公开(公告)号：US20090074874A1

公开(公告)日：2009-03-19

申请号：US12226693

申请日：2007-04-24

申请人： Yuko Amano ,  Yasuki Kato ,  Mitsunori Harada ,  Naoya Shibata ,  Hiroyuki Saito

发明人： Yuko Amano ,  Yasuki Kato ,  Mitsunori Harada ,  Naoya Shibata ,  Hiroyuki Saito

IPC分类号： A61K9/10

CPC分类号： A61K31/4745 ,  A61K9/1075 ,  A61K31/704 ,  A61K47/6907

摘要： The present invention provides a method of encapsulating a low molecular weight drug in a polymer micelle, the method comprising the steps of: (a) dissolving or dispersing the drug having an electric charge in an aqueous medium; (b) preparing an aqueous medium containing a polymer micelle comprising a block copolymer having an overall hydrophobic region and a hydrophilic region, the overall hydrophobic region containing hydrophobic side chains and side chains having an electric charge opposite to that of the low molecular weight drug in random order; (c) mixing the aqueous medium having the low molecular weight drug dissolved or dispersed therein and the aqueous medium containing the polymer micelle; and (d) adjusting the pH of the mixed aqueous medium to a pH at which the encapsulation of the low molecular weight drug is stabilized.

摘要翻译： 本发明提供一种将低分子量药物包封在聚合物胶束中的方法，该方法包括以下步骤：（a）将具有电荷的药物溶解或分散在水性介质中; （b）制备含有聚合物胶束的水性介质，所述聚合物胶束包含具有总疏水区域和亲水区域的嵌段共聚物，所述整个疏水区域含有疏水侧链和具有与低分子量药物相反的电荷的侧链 随机顺序; （c）将溶解或分散在其中的低分子量药物的水性介质和含有聚合物胶束的水性介质混合; 和（d）将混合水性介质的pH调节至低分子量药物的包封稳定的pH。

公开(公告)号：US20120093881A1

公开(公告)日：2012-04-19

申请号：US13258797

申请日：2011-02-07

申请人： Yasuki Kato ,  Mitsunori Harada ,  Miho Ohuchi

发明人： Yasuki Kato ,  Mitsunori Harada ,  Miho Ohuchi

IPC分类号： A61K9/00 ,  A61K38/02

CPC分类号： A61K9/1075 ,  A61K9/0019

摘要： A pharmaceutical composition containing a drug encapsulated in a polymer micelle composition containing a first block copolymer having affinity with HDL and a second block copolymer having affinity with a lipoprotein excluding HDL, each block copolymer having a hydrophobic polymer chain segment and a hydrophilic polymer chain segment such that a plurality of block copolymers arrange radially with the hydrophobic segments directed inward and the hydrophilic segments directed outward. In the composition, a detachment of the first block copolymer is induced by HDL adhesion which forms a gap and promotes the release of a drug encapsulated, while the second block copolymer excluding an affinity with HDL controls a release speed of the drug encapsulated.

摘要翻译： 一种药物组合物，其包含包含在与HDL亲和性的第一嵌段共聚物的聚合物胶束组合物中的药物和与除了HDL之外的脂蛋白具有亲和性的第二嵌段共聚物，每个嵌段共聚物具有疏水性聚合物链段和亲水性聚合物链段， 多个嵌段共聚物径向布置，其中疏水片段向内指向，亲水片段向外指向。 在组合物中，第一嵌段共聚物的脱离是由HDL粘附引起的，其形成间隙并促进包封的药物的释放，而不包括与HDL的亲和力的第二嵌段共聚物控制包封的药物的释放速度。

公开(公告)号：US08574601B2

公开(公告)日：2013-11-05

申请号：US13258797

申请日：2011-02-07

申请人： Yasuki Kato ,  Mitsunori Harada ,  Miho Ohuchi

发明人： Yasuki Kato ,  Mitsunori Harada ,  Miho Ohuchi

IPC分类号： A61K38/02 ,  A61K9/00

CPC分类号： A61K9/1075 ,  A61K9/0019

摘要： A pharmaceutical composition containing a drug encapsulated in a polymer micelle composition containing a first block copolymer having affinity with HDL and a second block copolymer having affinity with a lipoprotein excluding HDL, each block copolymer having a hydrophobic polymer chain segment and a hydrophilic polymer chain segment such that a plurality of block copolymers arrange radially with the hydrophobic segments directed inward and the hydrophilic segments directed outward. In the composition, a detachment of the first block copolymer is induced by HDL adhesion which forms a gap and promotes the release of a drug encapsulated, while the second block copolymer excluding an affinity with HDL controls a release speed of the drug encapsulated.

摘要翻译： 一种药物组合物，其包含包含在与HDL亲和性的第一嵌段共聚物的聚合物胶束组合物中的药物和与除了HDL之外的脂蛋白具有亲和性的第二嵌段共聚物，每个嵌段共聚物具有疏水性聚合物链段和亲水性聚合物链段， 多个嵌段共聚物径向布置，其中疏水片段向内指向，亲水片段向外指向。 在组合物中，第一嵌段共聚物的脱离是由HDL粘附引起的，其形成间隙并促进包封的药物的释放，而不包括与HDL的亲和力的第二嵌段共聚物控制包封的药物的释放速度。

公开(公告)号：US08147868B2

公开(公告)日：2012-04-03

申请号：US12309498

申请日：2007-04-25

申请人： Miho Ohuchi ,  Mitsunori Harada ,  Yuko Amano ,  Yasuki Kato

发明人： Miho Ohuchi ,  Mitsunori Harada ,  Yuko Amano ,  Yasuki Kato

IPC分类号： A61K9/127 ,  A61K38/00

CPC分类号： A61K9/1075 ,  A61K9/0019 ,  A61K38/00 ,  A61K47/34

摘要： The invention provides a physiologically active polypeptide- or protein-encapsulating polymer micelle composition derived from a block copolymer comprising hydrophilic segments and hydrophobic segments.

摘要翻译： 本发明提供了衍生自包含亲水片段和疏水片段的嵌段共聚物的生理活性多肽或蛋白质包封的聚合物胶束组合物。

公开(公告)号：US20090291130A1

公开(公告)日：2009-11-26

申请号：US12309498

申请日：2007-04-25

申请人： Miho Ohuchi ,  Mitsunori Harada ,  Yuko Amano ,  Yasuki Kato

发明人： Miho Ohuchi ,  Mitsunori Harada ,  Yuko Amano ,  Yasuki Kato

IPC分类号： A61K9/127 ,  A61K38/02

CPC分类号： A61K9/1075 ,  A61K9/0019 ,  A61K38/00 ,  A61K47/34

摘要： The invention provides a physiologically active polypeptide- or protein-encapsulating polymer micelle composition derived from a block copolymer comprising hydrophilic segments and hydrophobic segments.

摘要翻译： 本发明提供了衍生自包含亲水片段和疏水片段的嵌段共聚物的生理活性多肽或蛋白质包封的聚合物胶束组合物。