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1. 发明授权

US6080396A Anthracycline compound derivative and pharmaceutical preparation containing the same 失效
标题翻译：蒽环类化合物衍生物和含有它们的药物制剂
公开(公告)号：US6080396A
公开(公告)日：2000-06-27
申请号：US836965
申请日：1997-08-18
申请人： Masayuki Yokoyama , Kazunori Kataoka , Teruo Okano , Yasuhisa Sakurai , Shigeto Fukushima , Ryuji Uehara , Tomoko Akutsu , Kazuya Okamoto , Hiroko Mashiba , Megumi Machida , Kazuhisa Shimizu
发明人： Masayuki Yokoyama , Kazunori Kataoka , Teruo Okano , Yasuhisa Sakurai , Shigeto Fukushima , Ryuji Uehara , Tomoko Akutsu , Kazuya Okamoto , Hiroko Mashiba , Megumi Machida , Kazuhisa Shimizu
IPC分类号： A61K9/107 , A61K9/51 , A61K9/127 , A61K31/70 , C07M17/08
CPC分类号： A61K9/1075
摘要： A dimer, trimer or tetramer of an anthracycline compound which can be obtained by directly, chemically bonding anthracycline compounds having anticancer activities to each other by an alkali treatment. A high molecular block copolymer-drug complex pharmaceutical preparation in which the high molecular block copolymer having a hydrophilic polymer segment and a hydrophobic polymer segment forms a micelle having the hydrophilic segment as its outer shell and contains in its hydrophobic inner core a dimer, trimer or tetramer of anthracycline compound alone or together with other drugs. A high molecular block copolymer-drug complex pharmaceutical preparation in which the high molecular block copolymer having a hydrophilic polymer segment and a hydrophobic polymer segment forms a micelle having the hydrophilic segment as its outer shell and contains in its hydrophobic inner core an anthracycline anticancer agent, wherein, when the pharmaceutical preparation is intravenously administered to a CDF1 mouse, the amount of the anthracycline anticancer agent in 1 ml of the mouse blood plasma after 1 hour of its administration becomes 10 (% of dose/ml) or more, provided that the amount of anthracycline anticancer agent in the administered preparation is defined as 100. The aforementioned pharmaceutical preparations have high drug effects and low toxicities.
摘要翻译： PCT No.PCT / JP96 / 02789第 371日期：1997年8月18日 102（e）日期1997年8月18日PCT提交1996年9月26日PCT公布。公开号WO97 / 12895 日期1997年04月10日可以通过碱处理直接化学键合具有抗癌活性的蒽环类化合物而获得的蒽环类化合物的二聚体，三聚体或四聚体。一种高分子嵌段共聚物 - 药物复合药物制剂，其中具有亲水性聚合物链段和疏水性聚合物链段的高分子嵌段共聚物形成具有亲水链段作为其外壳的胶束，并且在其疏水内核中含有二聚体，三聚体或蒽环类化合物的四聚体单独或与其他药物一起。一种高分子嵌段共聚物 - 药物复合药物制剂，其中具有亲水性聚合物链段和疏水性聚合物链段的高分子嵌段共聚物形成具有亲水链段作为其外壳并在其疏水内核中含有蒽环类抗癌剂的胶束，其中，当向CDF1小鼠静脉内施用药物制剂时，在施用1小时后1ml小鼠血浆中的蒽环类抗癌剂的量为10（％/剂量）以上，条件是给药制剂中蒽环类抗癌剂的量定义为100.上述药物制剂具有高药物作用和低毒性。

2. 发明申请

US20120231053A1 Block Copolymer For Intraperitoneal Administration Containing Anti-Cancer Agent, Micelle Preparation Thereof, And Cancer Therapeutic Agent Comprising The Micelle Preparation As Active Ingredient 审中-公开
标题翻译：用于含有抗癌剂，其胶束制剂和包含作为活性成分的胶束制剂的癌症治疗剂的腹膜内给药的嵌段共聚物
公开(公告)号：US20120231053A1
公开(公告)日：2012-09-13
申请号：US13501460
申请日：2010-10-18
申请人： Yuichi Akatsu , Hiroko Mashiba
发明人： Yuichi Akatsu , Hiroko Mashiba
IPC分类号： A61K9/00 , A61K31/4745 , A61P35/04 , A61K31/337 , A61P35/00
CPC分类号： A61K9/146 , A61K9/0019 , A61K9/0021 , A61K9/1075 , A61K31/337 , A61K31/4375 , A61K47/34 , A61K47/59 , A61K47/60 , A61K47/645 , A61K47/6907
摘要： To provide a therapeutic method using a water soluble, high molecular weight block polymer to enable that an intraperitoneally administered anti-cancer agent may maintain for a long-term retention in the abdominal cavity to enoughly exert the effect of the anti-cancer agent and reduce adverse side-effects thereof.A therapeutic agent as a micelle preparation, comprising a copolymer having a hydrophilic polymeric moiety and a polycarboxylic acid derivative moiety; and an anti-cancer agent bonding to or encapsulated in the copolymer, wherein the micelle preparation may exhibit sustained drug release capability, and enables an extension of a retention time period of the anti-cancer agent in an abdominal cavity, is provided. A superior life-prolonging effect was found in an intraperitoneal administration mouse model compared with a case in which only an encapsulated drug is administered, and thus the present invention was completed accordingly.
摘要翻译：为了提供使用水溶性高分子量嵌段聚合物的治疗方法，使得腹膜内施用的抗癌剂可以维持在腹腔中的长期保留以足够发挥抗癌剂的作用并减少不良副作用。作为胶束制剂的治疗剂，包含具有亲水性聚合物部分和多元羧酸衍生物部分的共聚物; 和与该共聚物结合或包封的抗癌剂，其中胶束制剂可显示持续的药物释放能力，并且能够延长抗癌剂在腹腔中的保留时间。与仅给药包封药物的情况相比，在腹膜内给药小鼠模型中发现了优异的延长寿命，因此本发明相应地完成。

3. 发明授权

US07700709B2 Polymeric derivative of cytidine metabolic antagonist 有权
标题翻译：胞苷代谢拮抗剂的聚合衍生物
公开(公告)号：US07700709B2
公开(公告)日：2010-04-20
申请号：US11919912
申请日：2006-04-27
申请人： Akira Masuda , Takeshi Onda , Hiroko Mashiba , Keiichirou Yamamoto , Kazutoshi Takashio
发明人： Akira Masuda , Takeshi Onda , Hiroko Mashiba , Keiichirou Yamamoto , Kazutoshi Takashio
IPC分类号： C08G61/12
CPC分类号： C08G73/0233 , A61K47/60 , A61K47/645 , C08G65/329 , C08G65/3332 , C08G73/028
摘要： A derivative of a cytidine metabolic antagonist which can exert a high therapeutic effect at a low dose. A polymeric derivative of a cytidine metabolic antagonist which comprises a polymeric compound having a polyethylene glycol moiety and a polymer moiety having a carboxyl group in a side chain and a cytidine metabolic antagonist, which has such a structure that the carboxyl group in the side chain of the polymeric compound and an amino group in the cytidine metabolic antagonist are bound together to form an amide bond.
摘要翻译：胞苷代谢拮抗剂的衍生物，其可以在低剂量下发挥高治疗效果。胞苷代谢拮抗剂的聚合衍生物，其包含具有聚乙二醇部分的聚合化合物和在侧链具有羧基的聚合物部分和胞苷代谢拮抗剂，其具有以下结构：侧链中的羧基胞苷代谢拮抗剂中的高分子化合物和氨基结合在一起形成酰胺键。

4. 发明申请

US20090012252A1 Polymeric Derivative of Cytidine Metabolic Antagonist 有权
标题翻译：胞苷代谢拮抗剂的聚合衍生物
公开(公告)号：US20090012252A1
公开(公告)日：2009-01-08
申请号：US11919912
申请日：2006-04-27
申请人： Akira Masuda , Takeshi Onda , Hiroko Mashiba , Keiichirou Yamamoto , Kazutoshi Takashio
发明人： Akira Masuda , Takeshi Onda , Hiroko Mashiba , Keiichirou Yamamoto , Kazutoshi Takashio
IPC分类号： C08G83/00
CPC分类号： C08G73/0233 , A61K47/60 , A61K47/645 , C08G65/329 , C08G65/3332 , C08G73/028
摘要： [PROBLEMS] To provide a derivative of a cytidine metabolic antagonist which can exert a high therapeutic effect at a low dose.[MEANS FOR SOLVING PROBLEMS] A polymeric derivative of a cytidine metabolic antagonist which comprises a polymeric compound having a polyethylene glycol moiety and a polymer moiety having a carboxyl group in a side chain and a cytidine metabolic antagonist, which has such a structure that the carboxyl group in the side chain of the polymeric compound and an amino group in the cytidine metabolic antagonist are bound together to form an amide bond.
摘要翻译： [问题]提供可以以低剂量发挥高治疗效果的胞苷代谢拮抗剂的衍生物。解决问题的手段胞苷代谢拮抗剂的聚合衍生物包含具有聚乙二醇部分和侧链中具有羧基的聚合物部分和胞苷代谢拮抗剂的聚合物，其具有以下结构：羧基聚合化合物的侧链基团和胞苷代谢拮抗剂中的氨基结合在一起形成酰胺键。

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