公开(公告)号：US20130217871A1

公开(公告)日：2013-08-22

申请号：US13809203

申请日：2011-07-11

申请人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Saswata Lahiri ,  Nitin Gupta ,  Vivek Kumar ,  Mukesh Madan Mudgal

发明人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Saswata Lahiri ,  Nitin Gupta ,  Vivek Kumar ,  Mukesh Madan Mudgal

IPC分类号： C08B31/00

CPC分类号： C08B31/00 ,  A61K47/61

摘要： The present invention relates to hydroxyalkyl starch conjugates and a method for preparing the same, the hydroxyalkyl starch conjugate comprising a hydroxyalkyl starch derivative and a cytotoxic agent, the cytotoxic agent comprising at least one primary hydroxyl group, wherein the hydroxyalkyl starch is linked via said primary hydroxyl group to the cytotoxic agent. The conjugates according to the present invention have a structure according to the following formula HAS′(-L-M)n wherein M is a residue of the cytotoxic agent, L is a linking moiety, HAS′ is the residue of the hydroxyalkyl starch derivative, and n is greater than or equal to 1, and wherein the hydroxyalkyl starch derivative has a mean molecular weight (MW) above the renal threshold and a molar substitution (MS) in the range of from 0.6 to 1.5.

摘要翻译： 本发明涉及羟基烷基淀粉共轭物及其制备方法，包含羟烷基淀粉衍生物和细胞毒性剂的羟烷基淀粉缀合物，细胞毒性剂包含至少一个伯羟基，其中羟烷基淀粉通过所述初级 羟基对细胞毒性剂。 根据本发明的缀合物具有根据下式HAS'（ - LM）n的结构，其中M是细胞毒性剂的残基，L是连接部分，HAS'是羟烷基淀粉衍生物的残基，以及 n大于或等于1，其中羟烷基淀粉衍生物的平均分子量（MW）高于肾阈值，摩尔取代度（MS）在0.6至1.5的范围内。

公开(公告)号：US20140088298A9

公开(公告)日：2014-03-27

申请号：US13809194

申请日：2011-07-11

申请人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Frank Nocken ,  Saswata Lahiri ,  Nitin Gupta ,  Sunil Sanghani ,  Azim Abul ,  Hemant Kumar Singh ,  Sandeep Grewal ,  Sandeep Kaur

发明人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Frank Nocken ,  Saswata Lahiri ,  Nitin Gupta ,  Sunil Sanghani ,  Azim Abul ,  Hemant Kumar Singh ,  Sandeep Grewal ,  Sandeep Kaur

IPC分类号： A61K47/36

CPC分类号： A61K47/4823 ,  A61K47/36 ,  A61K47/61 ,  C08B31/10

摘要： The present invention relates to a hydroxyalkyl starch conjugate and a method for preparing the same, said hydroxy-yalkyl starch conjugate comprising a hydroxyalkyl starch derivative and a cytotoxic agent, the cytotoxic agent comprising at least one secondary hydroxyl group, wherein the hydroxyalkyl starch is linked via said secondary hydroxyl group to the cytotoxic agent. The conjugate according to the present invention has a structure according to the following formula HAS′(-L-M)n wherein M is a residue of the cytotoxic agent, L is a linking moiety, HAS′ is the residue of the hydroxyalkyl starch derivative, and n is greater than or equal to 1, and wherein the hydroxyalkyl starch derivative has a mean molecular weight (MW) above the renal threshold.

摘要翻译： 本发明涉及羟烷基淀粉缀合物及其制备方法，所述羟基 - 烷基淀粉缀合物包含羟烷基淀粉衍生物和细胞毒性剂，细胞毒性剂包含至少一个仲羟基，其中羟烷基淀粉连接 通过所述仲羟基与细胞毒性剂接触。 根据本发明的缀合物具有根据下式HAS'（ - LM）n的结构，其中M是细胞毒性剂的残基，L是连接部分，HAS'是羟烷基淀粉衍生物的残基，和 n大于或等于1，并且其中羟烷基淀粉衍生物具有高于肾阈值的平均分子量（MW）。

公开(公告)号：US20140073779A9

公开(公告)日：2014-03-13

申请号：US13809081

申请日：2011-07-11

申请人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Frank Nocken ,  Saswata Lahiri ,  Nitin Gupta ,  Sunil Sanghani ,  Azim Abul ,  Hemant Kumar Singh ,  Sandeep Grewal ,  Sandeep Kaur

发明人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Frank Nocken ,  Saswata Lahiri ,  Nitin Gupta ,  Sunil Sanghani ,  Azim Abul ,  Hemant Kumar Singh ,  Sandeep Grewal ,  Sandeep Kaur

IPC分类号： C08B31/10

CPC分类号： A61K47/4823 ,  A61K47/36 ,  A61K47/61 ,  C08B31/10

摘要： The present invention relates to a hydroxyalkyl starch conjugate and a method for preparing the same, said hydroxyalkyl starch conjugate comprising a hydroxyalkyl starch derivative and a cytotoxic agent, the cytotoxic agent comprising at least one secondary hydroxyl group, wherein the hydroxyalkyl starch is linked via said secondary hydroxyl group to the cytotoxic agent. The conjugate according to the present invention has a structure according to the following formula HAS′(-L-M)n wherein M is a residue of the cytotoxic agent, L is a linking moiety, HAS′ is the residue of the hydroxyalkyl starch derivative, and n is greater than or equal to 1, and wherein the hydroxyalkyl starch derivative has a mean molecular weight (MW) above the renal threshold.

摘要翻译： 本发明涉及羟烷基淀粉缀合物及其制备方法，所述羟烷基淀粉缀合物包含羟烷基淀粉衍生物和细胞毒性剂，所述细胞毒性剂包含至少一个仲羟基，其中所述羟烷基淀粉通过所述 仲羟基对细胞毒性剂。 根据本发明的缀合物具有根据下式HAS'（ - LM）n的结构，其中M是细胞毒性剂的残基，L是连接部分，HAS'是羟烷基淀粉衍生物的残基，和 n大于或等于1，并且其中羟烷基淀粉衍生物具有高于肾阈值的平均分子量（MW）。

公开(公告)号：US20130184455A1

公开(公告)日：2013-07-18

申请号：US13809081

申请日：2011-07-11

申请人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Frank Nocken ,  Saswata Lahiri ,  Nitin Gupta ,  Sunil Sanghani ,  Azim Abul ,  Hemant Kumar Singh ,  Sandeep Grewal ,  Sandeep Kaur

发明人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Frank Nocken ,  Saswata Lahiri ,  Nitin Gupta ,  Sunil Sanghani ,  Azim Abul ,  Hemant Kumar Singh ,  Sandeep Grewal ,  Sandeep Kaur

IPC分类号： C08B31/10

CPC分类号： A61K47/36 ,  A61K47/61 ,  C08B31/10

摘要： The present invention relates to a hydroxyalkyl starch conjugate and a method for preparing the same, said hydroxyalkyl starch conjugate comprising a hydroxyalkyl starch derivative and a cytotoxic agent, the cytotoxic agent comprising at least one secondary hydroxyl group, wherein the hydroxyalkyl starch is linked via said secondary hydroxyl group to the cytotoxic agent. The conjugate according to the present invention has a structure according to the following formula HAS′(-L-M)n wherein M is a residue of the cytotoxic agent, L is a linking moiety, HAS′ is the residue of the hydroxyalkyl starch derivative, and n is greater than or equal to 1, and wherein the hydroxyalkyl starch derivative has a mean molecular weight (MW) above the renal threshold.

摘要翻译： 本发明涉及羟烷基淀粉缀合物及其制备方法，所述羟烷基淀粉缀合物包含羟烷基淀粉衍生物和细胞毒性剂，所述细胞毒性剂包含至少一个仲羟基，其中所述羟烷基淀粉通过所述 仲羟基对细胞毒性剂。 根据本发明的缀合物具有根据下式HAS'（ - LM）n的结构，其中M是细胞毒性剂的残基，L是连接部分，HAS'是羟烷基淀粉衍生物的残基，和 n大于或等于1，并且其中羟烷基淀粉衍生物具有高于肾阈值的平均分子量（MW）。

公开(公告)号：US20130211060A1

公开(公告)日：2013-08-15

申请号：US13809194

申请日：2011-07-11

申请人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacker ,  Norbert Zander ,  Frank Nocken ,  Saswata Lahiri ,  Nitin Gupta ,  Sunil Sanghani ,  Azim Abul ,  Hemant Kumar Singh ,  Sandeep Grewal ,  Sandeep Kaur

发明人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacker ,  Norbert Zander ,  Frank Nocken ,  Saswata Lahiri ,  Nitin Gupta ,  Sunil Sanghani ,  Azim Abul ,  Hemant Kumar Singh ,  Sandeep Grewal ,  Sandeep Kaur

IPC分类号： A61K47/36

CPC分类号： A61K47/36 ,  A61K47/61 ,  C08B31/10

摘要： The present invention relates to a hydroxyalkyl starch conjugate and a method for preparing the same, said hydroxy-yalkyl starch conjugate comprising a hydroxyalkyl starch derivative and a cytotoxic agent, the cytotoxic agent comprising at least one secondary hydroxyl group, wherein the hydroxyalkyl starch is linked via said secondary hydroxyl group to the cytotoxic agent. The conjugate according to the present invention has a structure according to the following formula HAS′(-L-M)n wherein M is a residue of the cytotoxic agent, L is a linking moiety, HAS′ is the residue of the hydroxyalkyl starch derivative, and n is greater than or equal to 1, and wherein the hydroxyalkyl starch derivative has a mean molecular weight (MW) above the renal threshold.

摘要翻译： 本发明涉及羟烷基淀粉缀合物及其制备方法，所述羟基 - 烷基淀粉缀合物包含羟烷基淀粉衍生物和细胞毒性剂，细胞毒性剂包含至少一个仲羟基，其中羟烷基淀粉连接 通过所述仲羟基与细胞毒性剂接触。 根据本发明的缀合物具有根据下式HAS'（ - LM）n的结构，其中M是细胞毒性剂的残基，L是连接部分，HAS'是羟烷基淀粉衍生物的残基，和 n大于或等于1，并且其中羟烷基淀粉衍生物具有高于肾阈值的平均分子量（MW）。

公开(公告)号：US20130178437A1

公开(公告)日：2013-07-11

申请号：US13809069

申请日：2011-07-11

申请人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander

发明人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander

IPC分类号： C07H15/24

CPC分类号： C07H15/24 ,  A61K47/61

摘要： The present invention relates to hydroxyalkyl starch (HAS) conjugates and to a method for preparing the hydroxyalkyl starch (HAS) conjugates, the hydroxyalkyl starch (HAS) conjugates comprising a hydroxyalkyl starch derivative and a cytotoxic agent, said conjugate having a structure according the following formula HAS′(-M)n wherein M is a residue of a cytotoxic agent, the cytotoxic agent comprising a carbonyl group, HAS′ is a residue of the hydroxyalkyl starch derivative comprising at least one functional group X, n is greater than or equal to 1, and wherein the cytotoxic agent is linked via the carbonyl function present in the cytotoxic agent to the functional group X comprised in the hydroxyalkyl starch derivative, wherein the linkage via the carbonyl function is a cleavable linkage, which is capable of being cleaved in vivo so as to release the cytotoxic agent.

摘要翻译： 本发明涉及羟烷基淀粉（HAS）缀合物和制备羟烷基淀粉（HAS）偶联物的方法，包含羟烷基淀粉衍生物和细胞毒性剂的羟烷基淀粉（HAS）缀合物，所述缀合物具有下列结构： 式（M）n其中M是细胞毒性剂的残基，细胞毒性剂包含羰基，HAS'是包含至少一个官能团X的羟烷基淀粉衍生物的残基，n大于或等于 至1，并且其中细胞毒性剂通过存在于细胞毒性剂中的羰基官能团连接到包含在羟烷基淀粉衍生物中的官能团X，其中通过羰基官能团的键可切割键，其能够被切割 以释放细胞毒性剂。

公开(公告)号：US20140073778A9

公开(公告)日：2014-03-13

申请号：US13809074

申请日：2011-07-11

申请人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Frank Nocken

发明人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Frank Nocken

IPC分类号： C08B31/10

CPC分类号： C08B31/10 ,  A61K47/61 ,  C08B31/12 ,  C08L3/08

摘要： The present invention relates to hydroxyalkyl starch conjugates, a method for preparing the same, the hydroxyalkyl starch conjugate comprising a hydroxyalkyl starch derivative and a cytotoxic agent and the cytotoxic agent comprising at least one tertiary hydroxyl group, wherein the hydroxyalkyl starch is linked via said tertiary hydroxyl group to the cytotoxic agent. The conjugates according to the present invention have a structure according to the following formula HAS′(-L-M)n wherein M is a residue of the cytotoxic agent, L is a linking moiety, HAS′ is the residue of the hydroxyalkyl starch derivative, and n is greater than or equal to 1, and wherein the hydroxyalkyl starch derivative has a mean molecular weight (MW) above the renal threshold.

摘要翻译： 本发明涉及羟烷基淀粉共轭物，其制备方法，包含羟烷基淀粉衍生物和细胞毒性剂的羟烷基淀粉缀合物和包含至少一个叔羟基的细胞毒性剂，其中羟烷基淀粉通过所述第三级 羟基对细胞毒性剂。 根据本发明的缀合物具有根据下式HAS'（ - LM）n的结构，其中M是细胞毒性剂的残基，L是连接部分，HAS'是羟烷基淀粉衍生物的残基，以及 n大于或等于1，并且其中羟烷基淀粉衍生物具有高于肾阈值的平均分子量（MW）。

公开(公告)号：US20130184454A1

公开(公告)日：2013-07-18

申请号：US13809074

申请日：2011-07-11

申请人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Frank Nocken

发明人： Helmut Knoller ,  Dominik Heckmann ,  Frank Hacket ,  Norbert Zander ,  Frank Nocken

IPC分类号： C08B31/10

CPC分类号： C08B31/10 ,  A61K47/61 ,  C08B31/12 ,  C08L3/08

摘要： The present invention relates to hydroxyalkyl starch conjugates, a method for preparing the same, the hydroxyalkyl starch conjugate comprising a hydroxyalkyl starch derivative and a cytotoxic agent and the cytotoxic agent comprising at least one tertiary hydroxyl group, wherein the hydroxyalkyl starch is linked via said tertiary hydroxyl group to the cytotoxic agent. The conjugates according to the present invention have a structure according to the following formula HAS′(-L-M)n wherein M is a residue of the cytotoxic agent, L is a linking moiety, HAS′ is the residue of the hydroxyalkyl starch derivative, and n is greater than or equal to 1, and wherein the hydroxyalkyl starch derivative has a mean molecular weight (MW) above the renal threshold.

摘要翻译： 本发明涉及羟烷基淀粉共轭物，其制备方法，包含羟烷基淀粉衍生物和细胞毒性剂的羟烷基淀粉缀合物和包含至少一个叔羟基的细胞毒性剂，其中羟烷基淀粉通过所述第三级 羟基对细胞毒性剂。 根据本发明的缀合物具有根据下式HAS'（ - LM）n的结构，其中M是细胞毒性剂的残基，L是连接部分，HAS'是羟烷基淀粉衍生物的残基，以及 n大于或等于1，并且其中羟烷基淀粉衍生物具有高于肾阈值的平均分子量（MW）。

公开(公告)号：US20100297078A1

公开(公告)日：2010-11-25

申请号：US12747972

申请日：2008-12-15

申请人： Frank Hacket ,  Wolfram Eichner ,  Helmut Knoller ,  Andreas Mitsch ,  Martin Schimmel ,  Norbert Zander ,  Franziska Hauschild

发明人： Frank Hacket ,  Wolfram Eichner ,  Helmut Knoller ,  Andreas Mitsch ,  Martin Schimmel ,  Norbert Zander ,  Franziska Hauschild

IPC分类号： A61K38/21 ,  C08B31/12 ,  C07K14/56 ,  C07K14/505 ,  C07K14/535 ,  C07H7/02 ,  C07K1/00 ,  A61K38/18 ,  A61P35/00 ,  A61P35/02 ,  A61P1/16 ,  A61P7/06 ,  A61P13/12 ,  A61P31/18

CPC分类号： C08B31/12 ,  A61K47/61

摘要： A method of producing a hydroxyalkyl starch (HAS) derivative, comprising a) reacting optionally oxidized hydroxyalkyl starch with a compound (D) comprising at least two functional groups —O—NH2 or a salt thereof, and b) reacting the hydroxyalkyl starch derivative obtained in step a) with a compound (L) comprising at least two functional groups W1 and W2 independently selected from the group consisting of an aldehyde group, a suitably protected aldehyde group, a keto group, and a suitably protected keto group.

摘要翻译： 一种制备羟烷基淀粉（HAS）衍生物的方法，包括：a）任选地氧化的羟烷基淀粉与包含至少两个官能团-O-NH 2或其盐的化合物（D）反应，和b）使获得的羟烷基淀粉衍生物 在步骤a）中，使用包含至少两个官能团W1和W2的化合物（L），其独立地选自醛基，适当保护的醛基，酮基和适当保护的酮基。

公开(公告)号：US08404834B2

公开(公告)日：2013-03-26

申请号：US12747981

申请日：2008-12-15

申请人： Frank Hacket ,  Thomas Hey ,  Franziska Hauschild ,  Helmut Knoller ,  Martin Schimmel ,  Klaus Sommermeyer

发明人： Frank Hacket ,  Thomas Hey ,  Franziska Hauschild ,  Helmut Knoller ,  Martin Schimmel ,  Klaus Sommermeyer

IPC分类号： C08B31/00 ,  C08B31/18 ,  C08B35/00

CPC分类号： C08B31/00 ,  A61K47/61 ,  C08B31/125

摘要： The invention relates to a method for the preparation of a hydroxyalkyl starch derivative which comprises reacting hydroxyalkyl starch (HAS) via the optionally oxidized reducing end of the HAS with the amino group M of a crosslinking compound which, apart from the amino group, comprises a specifically protected carbonyl group, namely an acetal group or a ketal group.

摘要翻译： 本发明涉及一种制备羟烷基淀粉衍生物的方法，其包括将羟烷基淀粉（HAS）经由任选氧化的HAS还原端与交联化合物的氨基M反应，所述交联化合物除了氨基外，还包含 特别保护的羰基，即缩醛基或缩酮基。