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1. 发明申请

US20060025330A1 Electrostatic bonding type macromolecular micelle drug carrier and drug carried thereon 审中-公开
公开(公告)号：US20060025330A1
公开(公告)日：2006-02-02
申请号：US11230564
申请日：2005-09-21
申请人： Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka , Masayuki Yokoyama , Satoshi Katayose , Satoru Suwa , Atsushi Harada
发明人： Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka , Masayuki Yokoyama , Satoshi Katayose , Satoru Suwa , Atsushi Harada
IPC分类号： A61K48/00 , A61K38/22
CPC分类号： A61K9/1075
摘要： The present invention provides an electrostatic bonding macromolecular micelle drug carrier comprising a block copolymer having a non-chargeable segment and a chargeable segment, for stably carrying a chargeable drug tending to be easily decomposed in vivo such as protein and DNA.

2. 发明授权

US5449513A Physical trapping type polymeric micelle drug preparation 失效
标题翻译：物理捕获型聚合胶束药物制剂
公开(公告)号：US5449513A
公开(公告)日：1995-09-12
申请号：US105535
申请日：1993-08-11
申请人： Masayuki Yokoyama , Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka
发明人： Masayuki Yokoyama , Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka
IPC分类号： A61K9/00 , A61K9/107 , A61K9/51 , A61K47/34 , A61K47/48 , C08G69/10 , A61K9/127 , A61K31/74
CPC分类号： C08G69/10 , A61K9/1075 , Y10T428/2985 , Y10T428/2989
摘要： The present invention relates to drug carriers composed of a block copolymer having hydrophilic and hydrophobic segments, a polymeric micelle type drug comprising hydrophobic drugs trapped by physical treatments in said drug carrier and methods for trapping hydrophobic drugs in the drug carrier. The drugs carrier composed of the block copolymer according to the invention forms a stable polymeric micelle structure with which hydrophobic drugs can be incorporated very efficiently via physical trapping. It was found that the incorporated drug is stably maintained in micelles even in the presence of serum. In addition, a drug difficult to administer into the living body owing to sparing water-solubility for its high hydrophobicity can be administered in the form of polymeric micelle drug.
摘要翻译：本发明涉及由具有亲水和疏水性片段的嵌段共聚物组成的药物载体，包含通过所述药物载体中的物理治疗而被捕获的疏水性药物的聚合物胶束型药物和用于在药物载体中捕获疏水性药物的方法。由根据本发明的嵌段共聚物组成的药物载体形成稳定的聚合胶束结构，通过物理捕获可以非常有效地引入疏水性药物。发现即使在血清存在下，掺入的药物稳定地保持在胶束中。此外，由于疏水性高的水溶性而难以施用于生物体的药物可以以聚合物胶束药物的形式施用。

3. 发明授权

US5483008A Polyether having heterofunctional groups at both ends, process for the preparation thereof and polymerization initiator therefor 失效
标题翻译：在两端具有杂官能团的聚醚，其制备方法和聚合引发剂
公开(公告)号：US5483008A
公开(公告)日：1996-01-09
申请号：US14285
申请日：1993-02-05
申请人： Yasuhisa Sakurai , Teruo Okano , Masayuki Yokoyama , Kazunori Kataoka , Yukio Nagasaki , Nobuyuki Ohsako , Masao Kato
发明人： Yasuhisa Sakurai , Teruo Okano , Masayuki Yokoyama , Kazunori Kataoka , Yukio Nagasaki , Nobuyuki Ohsako , Masao Kato
IPC分类号： C08G65/26 , C08G65/329 , C08G65/334 , C08G65/10 , C08G65/32
CPC分类号： C08G65/3348 , C08G65/2639 , C08G65/329
摘要： The present invention relates to a bifunctional polyether having groups different from each other at both ends, with a polymerization degree of 5 to 10000 and consisting of repeating units each represented by the following formula (I): ##STR1## (wherein R.sub.1, represents a hydrogen atom, halogen atom, or a lower alkyl group optionally substituted by a halogen atom, and R.sub.1 in each repeating unit may be the same or different), as well as to a process for the preparation thereof and a polymerization initiator therefor. The process of production and polymerization initiator of the present invention enable 100% introduction of a primary amino group into one of the ends of polyether.
摘要翻译：本发明涉及两端具有不同基团的双官能聚醚，聚合度为5〜10000，由下式（I）表示的重复单元构成：其中R1 表示氢原子，卤素原子或任选被卤素原子取代的低级烷基，各重复单元中的R 1可以相同或不同），以及其制备方法及其聚合引发剂。本发明的制备和聚合引发剂的方法可以将100％的伯氨基引入聚醚的一个端部。

4. 发明授权

US5478575A Polymers having benzeneboronic acid groups and insulin complexes of same of a sugar response type 失效
标题翻译：具有苯硼酸基团的聚合物和具有糖响应型的相同的胰岛素复合物
公开(公告)号：US5478575A
公开(公告)日：1995-12-26
申请号：US37383
申请日：1993-03-26
申请人： Tsuyoshi Miyazaki , Yoshishige Murata , Daijiro Shiino , Kazunori Waki , Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka , Yoshiyuki Koyama , Masayuki Yokoyama , Shigeru Kitano
发明人： Tsuyoshi Miyazaki , Yoshishige Murata , Daijiro Shiino , Kazunori Waki , Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka , Yoshiyuki Koyama , Masayuki Yokoyama , Shigeru Kitano
IPC分类号： A61K9/00 , A61K47/32 , A61K47/36 , A61K47/48 , A61K38/28
CPC分类号： A61K9/0019 , A61K47/32 , A61K47/36 , A61K47/48176 , A61K47/4823 , Y10S514/866
摘要： The present invention provides a polymer complex of a sugar response type having boronic acid groups in the polymer. Medicines may be contained or linked, preferably, the medicines have hydroxy groups. The polymer having boronic acid groups and the medicine having hydroxy groups may be linked by boronic acid ester bonds. The complex may also comprises polymers having boronic acid groups and polymers having hydroxy groups, and these polymers may be cross-linked.
摘要翻译：本发明提供了在聚合物中具有硼酸基团的糖响应型聚合物复合物。药物可以包含或连接，优选地，药物具有羟基。具有硼酸基团的聚合物和具有羟基的药物可以通过硼酸酯键连接。络合物还可以包含具有硼酸基团的聚合物和具有羟基的聚合物，并且这些聚合物可以是交联的。

5. 发明授权

US5412072A Water soluble high molecular weight polymerized drug preparation 失效
标题翻译：水溶性高分子量聚合药物制剂
公开(公告)号：US5412072A
公开(公告)日：1995-05-02
申请号：US496741
申请日：1990-03-21
申请人： Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka , Noriko Yamada , Shohei Inoue , Masayuki Yokoyama
发明人： Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka , Noriko Yamada , Shohei Inoue , Masayuki Yokoyama
IPC分类号： A61K31/70 , A61K9/00 , A61K31/785 , A61K47/42 , A61K47/48 , A61P35/00 , C08G69/10 , C08G69/40 , C08G69/48 , C07K9/00
CPC分类号： A61K47/48315
摘要： This invention is a water-soluble high molecular polymerized drug comprising a water-soluble clock copolymer having a hydrophilic segment and a hydrophobic pharmacological-functioning segment to side chain of which a drug is bonded. The hydrophilic first segments of the present invention include polyethylene glycol, polysaccharides, polyacrylamide, and so on. The hydrophobic segments being attached to a drug include polyaspartic acid, polyglutamic acid, polylysine, or derivatives thereof. Drugs to be attached to the hydrophobic segment include anti-cancer drugs, drugs for central nerve, drugs for circulatory organs, and so on.
摘要翻译：本发明是一种水溶性高分子聚合药物，其包含水溶性时钟共聚物，该水溶性时钟共聚物具有亲水链段和与药物结合的侧链的疏水性药理功能性区段。本发明的亲水性第一链段包括聚乙二醇，多糖，聚丙烯酰胺等。附着于药物的疏水性片段包括聚天冬氨酸，聚谷氨酸，聚赖氨酸或其衍生物。附着于疏水性片段的药物包括抗癌药物，中枢神经药物，循环器官药物等。

6. 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。

7. 发明授权

US5693751A Water soluble high molecular weight polymerized drug preparation 失效
标题翻译：水溶性高分子量聚合药物制剂
公开(公告)号：US5693751A
公开(公告)日：1997-12-02
申请号：US400905
申请日：1995-03-08
申请人： Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka , Noriko Yamada , Shohei Inoue , Masayuki Yokoyama
发明人： Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka , Noriko Yamada , Shohei Inoue , Masayuki Yokoyama
IPC分类号： A61K31/70 , A61K9/00 , A61K31/785 , A61K47/42 , A61K47/48 , A61P35/00 , C08G69/10 , C08G69/40 , C08G69/48 , C07K9/00
CPC分类号： A61K47/48315
摘要： This invention is a water-soluble high molecular polymerized drug comprising a water-soluble clock copolymer having a hydrophilic segment and a hydrophobic pharmacological-functioning segment to side chain of which a drug is bonded. The hydrophilic first segments of the present invention include polyethylene glycol, polysaccharides, polyacrylamide, and so on. The hydrophobic segments being attached to a drug include polyaspartic acid, polyglutamic acid, polylysine, or derivatives thereof. Drugs to be attached to the hydrophobic segment include anti-cancer drugs, drugs for central nerve, drugs for circulatory organs, and so on.
摘要翻译：本发明是一种水溶性高分子聚合药物，其包含水溶性时钟共聚物，该水溶性时钟共聚物具有亲水链段和与药物结合的侧链的疏水性药理功能性区段。本发明的亲水性第一链段包括聚乙二醇，多糖，聚丙烯酰胺等。附着于药物的疏水性片段包括聚天冬氨酸，聚谷氨酸，聚赖氨酸或其衍生物。附着于疏水性片段的药物包括抗癌药物，中枢神经药物，循环器官药物等。

8. 发明授权

US5679765A Polyether having heterofunctional groups at both ends, process for the preparation thereof and polymerization initiator therefor 失效
标题翻译：在两端具有杂官能团的聚醚，其制备方法和聚合引发剂
公开(公告)号：US5679765A
公开(公告)日：1997-10-21
申请号：US680781
申请日：1996-07-16
申请人： Yasuhisa Sakurai , Teruo Okano , Masayuki Yokoyama , Kazunori Kataoka , Yukio Nagasaki , Nobuyuki Ohsako , Masao Kato
发明人： Yasuhisa Sakurai , Teruo Okano , Masayuki Yokoyama , Kazunori Kataoka , Yukio Nagasaki , Nobuyuki Ohsako , Masao Kato
IPC分类号： C08G65/10 , C07C213/04 , C07C217/08 , C07C217/50 , C08G65/02 , C08G65/32 , C08G65/334 , C08G65/336 , C08G59/68 , C08G65/04
CPC分类号： C08G65/3348 , C08G65/336
摘要： The present invention relates to a bifunctional polyether having groups different from each other at both ends, with a polymerization degree of 5 to 10000 and consisting of repeating units each represented by the following formula (I): ##STR1## (wherein R.sub.1, represents a hydrogen atom, halogen atom, or a lower alkyl group optionally substituted by a halogen atom, and R.sub.1 in each repeating unit may be the same or different), as well as to a process for the preparation thereof and a polymerization initiator therefor. The process of production and polymerization initiator of the present invention enable 100% introduction of a primary amino group into one of the ends of polyether.
摘要翻译：本发明涉及两端具有不同基团的双官能聚醚，聚合度为5〜10000，由下式（I）表示的重复单元构成：其中R1 表示氢原子，卤素原子或任选被卤素原子取代的低级烷基，各重复单元中的R 1可以相同或不同），以及其制备方法及其聚合引发剂。本发明的制备和聚合引发剂的方法可以将100％的伯氨基引入聚醚的一个端部。

9. 发明授权

US5510103A Physical trapping type polymeric micelle drug preparation 失效
公开(公告)号：US5510103A
公开(公告)日：1996-04-23
申请号：US465499
申请日：1995-06-05
申请人： Masayuki Yokoyama , Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka
发明人： Masayuki Yokoyama , Yasuhisa Sakurai , Teruo Okano , Kazunori Kataoka
IPC分类号： A61K9/00 , A61K9/107 , A61K9/51 , A61K47/34 , A61K47/48 , C08G69/10 , A61K31/74 , A61K9/127
CPC分类号： C08G69/10 , A61K9/1075 , Y10T428/2985 , Y10T428/2989
摘要： The present invention relates to drug carriers composed of a block copolymer having hydrophilic and hydrophobic segments, a polymeric micelle type drug comprising hydrophobic drugs trapped by physical treatments in said drug carrier and methods for trapping hydrophobic drugs in the drug carrier. The drugs carrier composed of the block copolymer according to the invention forms a stable polymeric micelle structure with which hydrophobic drugs can be incorporated very efficiently via physical trapping. It was found that the incorporated drug is stably maintained in micelles even in the presence of serum. In addition, a drug difficult to administer into the living body owing to sparing water-solubility for its high hydrophobicity can be administered in the form of polymeric micelle drug.

10. 发明授权

US07125546B2 Polymeric micelle containing cisplatin enclosed therein and use thereof 有权
标题翻译：含有顺铂的聚合胶束包封在其中并用于其中
公开(公告)号：US07125546B2
公开(公告)日：2006-10-24
申请号：US10381339
申请日：2001-09-26
申请人： Kazunori Kataoka , Nobuhiro Nishiyama , Masayuki Yokoyama , Teruo Okano
发明人： Kazunori Kataoka , Nobuhiro Nishiyama , Masayuki Yokoyama , Teruo Okano
IPC分类号： A61K47/48 , A61K31/74 , A61K9/14 , A61K33/24 , A61K31/282 , A61K47/32 , A61K31/28 , A01N59/26 , A01N55/02
CPC分类号： C08G69/44 , A61K9/1075 , A61K33/24 , A61K38/00 , A61K47/60 , A61K47/645 , A61K47/6907 , C08G69/40 , C08G73/0233
摘要： Provided is a complex comprising cisplatin encapsulated therein in a form in which a chlorine ion thereof is ligand-exchanged with a carboxyl anion of a block copolymer comprising poly(ethylene glycol)-poly(glutamic acid). This complex can be a medicinal preparation to which a novel dosage form decreased in toxicity can be applied.
摘要翻译：提供了包含其中包含顺铂的复合物，其中其氯离子与包含聚（乙二醇） - 聚（谷氨酸）的嵌段共聚物的羧基阴离子配位交换的形式。该复合物可以是可以应用毒性降低的新型剂型的药物制剂。

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