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81. 发明专利

AU2006291527A1 Conjugates of hydroxyalkyl starch and an active substance, prepared by chemical ligation via thiazolidine 未知
公开(公告)号：AU2006291527A1
公开(公告)日：2007-03-22
申请号：AU2006291527
申请日：2006-09-12
申请人： FRESENIUS KABI DE GMBH
发明人： KNOLLER HELMUT , ZANDER NORBERT
IPC分类号： A61K47/48 , C08B31/00
摘要： The present invention relates to a method for preparing conjugates of an active substance and hydroxyalkyl starch and to conjugates of an active substance and hydroxyalkyl starch, preferably hydroxyethyl starch, wherein the conjugates are prepared by covalently linking the hydroxyalkyl starch and the active substance by a chemical residue having a structure according to formula (I) or formula (I') or formula (I") wherein R 1 , R 2 , R 2' , R 3 , R 3' and R 4 are independently selected from the group consisting of hydrogen, an optionally suitably substituted, linear, cyclic and/or branched alkyl, aryl, heteroaryl, aralkyl, and heteroaralkyl group, preferably hydrogen.

82. 发明专利

HK1089683A1 CONJUGATES OF HYDROXYALKYL STARCH AND G-CSF 未知
公开(公告)号：HK1089683A1
公开(公告)日：2006-12-08
申请号：HK06110272
申请日：2006-09-15
申请人： FRESENIUS KABI DE GMBH
发明人： EICHNER WOLFRAM , KNOLLER HELMUT , LUTTERBECK KATHARINA , ZANDER NORBERT , FRANK RONALD , SOMMERMEYER KLAUS , CONRADT HARALD S , GRABENHORST ECKART
IPC分类号： A61K20060101 , A61P20060101
摘要： The present invention relates to conjugates of hydroxyalkyl starch and a granulocyte colony stimulating factor protein (G-CSF) wherein these conjugates are formed by a covalent linkage between the hydroxyalkyl starch or a derivative of the hydroxyalkyl starch and the protein. The present invention also relates to the methods of producing these conjugates and the use of these conjugates.

83. 发明专利

DE60304640D1 未知
公开(公告)号：DE60304640D1
公开(公告)日：2006-05-24
申请号：DE60304640
申请日：2003-09-11
申请人： FRESENIUS KABI DE GMBH
发明人： CONRADT HARALD S , GRABENHORST ECKART , NIMTZ MANFRED , ZANDER NORBERT , FRANK RONALD , EICHNER WOLFRAM
IPC分类号： C07K14/505 , A61K8/73 , A61K9/00 , A61K9/14 , A61K38/00 , A61K38/18 , A61K47/48 , C07K14/53 , C07K14/54 , C07K14/55 , C07K14/56 , C07K14/565 , C07K17/06 , C07K17/10 , C08B31/00 , C08B31/08 , C08B31/12 , C08B33/04 , C08B35/04 , C12N15/12
摘要： Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch at its reducing end with amino compound. The reducing end is not oxidized prior to the reaction. Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch of formula (I) at its reducing end with amino compound of formula R a-NH-R b (II). [Image] R 1-R 3H, linear or branched hydroxyalkyl; R aat least one functional group X capable of reacting with at least one other compound prior to or after the reaction; R ba functional group X or W; W : -NH-, -NH-C(=G)-, -NH-C(=G)-G-, -NH-S(O) 2- or -NH-C(=G)-NH-; X : -SH, -NH 2, -O-NH 2, -NH-O-alkyl, -C(=G)-NH-NH 2, -G-C(=G)-NH-NH 2, -NH-C(=G)-NH-NH 2 or -S(O) 2-NH-NH 2; and G : O or S. An independent claim is included for a pharmaceutical composition comprising the hydroxyalkyl starch derivative (where the reaction product of (I) with (II) is reacted via the functional group X in (II) with the further compound (III) or (II) is reacted via the functional group X with (III) prior to the reaction with (I), and the reaction product of (I) and (II) with the crosslinking compound is reacted with a polypeptide). ACTIVITY : Antianemic. Hydroxyethyl starch-erythropoietin (HES-EPO) was tested by the EPO-bioassay in normocythaemic mouse system and showed specific activity of 344000 U/mg, which was 3 fold higher than international BRP-erythropoietin reference standard preparation. MECHANISM OF ACTION : None given.

84. 发明专利

AT323723T 未知
公开(公告)号：AT323723T
公开(公告)日：2006-05-15
申请号：AT03020423
申请日：2003-09-11
申请人： FRESENIUS KABI DE GMBH
发明人： CONRADT HARALD S , GRABENHORST ECKART , NIMTZ MANFRED , ZANDER NORBERT , FRANK RONALD , EICHNER WOLFRAM
IPC分类号： A61K8/73 , A61K9/00 , A61K9/14 , A61K38/00 , A61K38/18 , A61K47/48 , C07K14/505 , C07K14/53 , C07K14/54 , C07K14/55 , C07K14/56 , C07K14/565 , C07K17/06 , C07K17/10 , C08B31/00 , C08B31/08 , C08B31/12 , C08B33/04 , C08B35/04 , C12N15/12
摘要： Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch at its reducing end with amino compound. The reducing end is not oxidized prior to the reaction. Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch of formula (I) at its reducing end with amino compound of formula R a-NH-R b (II). [Image] R 1-R 3H, linear or branched hydroxyalkyl; R aat least one functional group X capable of reacting with at least one other compound prior to or after the reaction; R ba functional group X or W; W : -NH-, -NH-C(=G)-, -NH-C(=G)-G-, -NH-S(O) 2- or -NH-C(=G)-NH-; X : -SH, -NH 2, -O-NH 2, -NH-O-alkyl, -C(=G)-NH-NH 2, -G-C(=G)-NH-NH 2, -NH-C(=G)-NH-NH 2 or -S(O) 2-NH-NH 2; and G : O or S. An independent claim is included for a pharmaceutical composition comprising the hydroxyalkyl starch derivative (where the reaction product of (I) with (II) is reacted via the functional group X in (II) with the further compound (III) or (II) is reacted via the functional group X with (III) prior to the reaction with (I), and the reaction product of (I) and (II) with the crosslinking compound is reacted with a polypeptide). ACTIVITY : Antianemic. Hydroxyethyl starch-erythropoietin (HES-EPO) was tested by the EPO-bioassay in normocythaemic mouse system and showed specific activity of 344000 U/mg, which was 3 fold higher than international BRP-erythropoietin reference standard preparation. MECHANISM OF ACTION : None given.

85. 发明专利

NO20061121A 未知
公开(公告)号：NO20061121A
公开(公告)日：2006-05-05
申请号：NO20061121
申请日：2006-03-08
申请人： FRESENIUS KABI DE GMBH
发明人： EICHNER WOLFRAM , ZANDER NORBERT , FRANK RONALD , KNOLLER HELMUT , LUTTERBECK KATHARINA , SOMMERMEYER KLAUS , CONRADT HARALD S , GRABESHORST ECKART
IPC分类号： A61K47/48
CPC分类号： C07K14/535 , A61K47/61

86. 发明专利

PL375037A1 HYDROXYALKYL STARCH DERIVATIVES 未知
公开(公告)号：PL375037A1
公开(公告)日：2005-11-14
申请号：PL37503703
申请日：2003-08-08
申请人： FRESENIUS KABI DE GMBH
发明人： CONRADT HARALD , EICHNER WOLFRAM , ZANDER NORBERT
IPC分类号： A61K8/73 , A61K9/00 , A61K9/14 , A61K38/00 , A61K38/18 , A61K47/48 , C07K14/505 , C07K14/53 , C07K14/54 , C07K14/55 , C07K14/56 , C07K14/565 , C07K17/06 , C07K17/10 , C08B31/00 , C08B31/08 , C08B31/12 , C08B33/04 , C08B35/04 , C12N15/12
摘要： Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch at its reducing end with amino compound. The reducing end is not oxidized prior to the reaction. Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch of formula (I) at its reducing end with amino compound of formula R a-NH-R b (II). [Image] R 1-R 3H, linear or branched hydroxyalkyl; R aat least one functional group X capable of reacting with at least one other compound prior to or after the reaction; R ba functional group X or W; W : -NH-, -NH-C(=G)-, -NH-C(=G)-G-, -NH-S(O) 2- or -NH-C(=G)-NH-; X : -SH, -NH 2, -O-NH 2, -NH-O-alkyl, -C(=G)-NH-NH 2, -G-C(=G)-NH-NH 2, -NH-C(=G)-NH-NH 2 or -S(O) 2-NH-NH 2; and G : O or S. An independent claim is included for a pharmaceutical composition comprising the hydroxyalkyl starch derivative (where the reaction product of (I) with (II) is reacted via the functional group X in (II) with the further compound (III) or (II) is reacted via the functional group X with (III) prior to the reaction with (I), and the reaction product of (I) and (II) with the crosslinking compound is reacted with a polypeptide). ACTIVITY : Antianemic. Hydroxyethyl starch-erythropoietin (HES-EPO) was tested by the EPO-bioassay in normocythaemic mouse system and showed specific activity of 344000 U/mg, which was 3 fold higher than international BRP-erythropoietin reference standard preparation. MECHANISM OF ACTION : None given.

87. 发明专利

PL374490A1 HASYLATED POLYPEPTIDES, ESPECIALLY HASYLATED ERYTHROPOIETIN 未知
公开(公告)号：PL374490A1
公开(公告)日：2005-10-31
申请号：PL37449003
申请日：2003-08-08
申请人： FRESENIUS KABI DE GMBH
发明人： CONRADT HARALD S , GRABENHORST ECKART , NIMTZ MANFRED , ZANDER NORBERT , FRANK RONALD , EICHNER WOLFRAM
IPC分类号： A61K8/73 , A61K9/00 , A61K9/14 , A61K38/00 , A61K38/18 , A61K47/48 , C07K14/505 , C07K14/53 , C07K14/54 , C07K14/55 , C07K14/56 , C07K14/565 , C07K17/06 , C07K17/10 , C08B31/00 , C08B31/08 , C08B31/12 , C08B33/04 , C08B35/04 , C12N15/12
摘要： Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch at its reducing end with amino compound. The reducing end is not oxidized prior to the reaction. Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch of formula (I) at its reducing end with amino compound of formula R a-NH-R b (II). [Image] R 1-R 3H, linear or branched hydroxyalkyl; R aat least one functional group X capable of reacting with at least one other compound prior to or after the reaction; R ba functional group X or W; W : -NH-, -NH-C(=G)-, -NH-C(=G)-G-, -NH-S(O) 2- or -NH-C(=G)-NH-; X : -SH, -NH 2, -O-NH 2, -NH-O-alkyl, -C(=G)-NH-NH 2, -G-C(=G)-NH-NH 2, -NH-C(=G)-NH-NH 2 or -S(O) 2-NH-NH 2; and G : O or S. An independent claim is included for a pharmaceutical composition comprising the hydroxyalkyl starch derivative (where the reaction product of (I) with (II) is reacted via the functional group X in (II) with the further compound (III) or (II) is reacted via the functional group X with (III) prior to the reaction with (I), and the reaction product of (I) and (II) with the crosslinking compound is reacted with a polypeptide). ACTIVITY : Antianemic. Hydroxyethyl starch-erythropoietin (HES-EPO) was tested by the EPO-bioassay in normocythaemic mouse system and showed specific activity of 344000 U/mg, which was 3 fold higher than international BRP-erythropoietin reference standard preparation. MECHANISM OF ACTION : None given.

88. 发明专利

CA2558738A1 CONJUGATES OF HYDROXYALKYL STARCH AND A PROTEIN, PREPARED BYREDUCTIVE AMINATION 未知
公开(公告)号：CA2558738A1
公开(公告)日：2005-10-06
申请号：CA2558738
申请日：2005-03-11
申请人： FRESENIUS KABI DE GMBH
发明人： CONRADT HARALD , EICHNER WOLFRAM , HACKET FRANK , ZANDER NORBERT , LANGER KLAUS , ORLANDO MICHELE , FRANK RONALD
IPC分类号： C08B31/00 , A61K38/18 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K38/42 , A61K38/44 , A61K38/48 , A61K38/55 , A61K47/48 , A61K51/06 , A61K51/08 , C07K14/00 , C08B31/18
摘要： The present invention relates to conjugates of hydroxyalkyl starch, preferably hydroxyethyl starch, and a protein, wherein these conjugates are formed by a reductive amination reaction between at least one aldehyde group or keto group or hemiacetal group of the hydroxyalkyl starch or of a derivative of the hydroxyalkyl starch, and at least one amino group of the protein, so that the hydroxyalkyl starch or the derivative thereof is covalently linked to the protein via an azomethine linkage or a amino linkage. The present invention also relates to the method of producing these conjugates and specific uses of the conjugates.

89. 发明专利

BR0314107A 未知
公开(公告)号：BR0314107A
公开(公告)日：2005-07-19
申请号：BR0314107
申请日：2003-08-08
申请人： FRESENIUS KABI DE GMBH
发明人： ZANDER NORBERT
IPC分类号： A61K8/73 , A61K9/00 , A61K9/14 , A61K38/00 , A61K38/18 , A61K47/48 , C07K14/505 , C07K14/53 , C07K14/54 , C07K14/55 , C07K14/56 , C07K14/565 , C07K17/06 , C07K17/10 , C08B31/00 , C08B31/08 , C08B31/12 , C08B33/04 , C08B35/04 , C12N15/12
摘要： Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch at its reducing end with amino compound. The reducing end is not oxidized prior to the reaction. Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch of formula (I) at its reducing end with amino compound of formula R a-NH-R b (II). [Image] R 1-R 3H, linear or branched hydroxyalkyl; R aat least one functional group X capable of reacting with at least one other compound prior to or after the reaction; R ba functional group X or W; W : -NH-, -NH-C(=G)-, -NH-C(=G)-G-, -NH-S(O) 2- or -NH-C(=G)-NH-; X : -SH, -NH 2, -O-NH 2, -NH-O-alkyl, -C(=G)-NH-NH 2, -G-C(=G)-NH-NH 2, -NH-C(=G)-NH-NH 2 or -S(O) 2-NH-NH 2; and G : O or S. An independent claim is included for a pharmaceutical composition comprising the hydroxyalkyl starch derivative (where the reaction product of (I) with (II) is reacted via the functional group X in (II) with the further compound (III) or (II) is reacted via the functional group X with (III) prior to the reaction with (I), and the reaction product of (I) and (II) with the crosslinking compound is reacted with a polypeptide). ACTIVITY : Antianemic. Hydroxyethyl starch-erythropoietin (HES-EPO) was tested by the EPO-bioassay in normocythaemic mouse system and showed specific activity of 344000 U/mg, which was 3 fold higher than international BRP-erythropoietin reference standard preparation. MECHANISM OF ACTION : None given.

90. 发明专利

HK1063475A1 Hasylated polypeptides, especially hasylated erythropoietin 未知
公开(公告)号：HK1063475A1
公开(公告)日：2004-12-31
申请号：HK04106171
申请日：2004-08-18
申请人： FRESENIUS KABI DE GMBH
发明人： CONRADT HARALD S , GRABENHORST ECKART , NIMTZ MANFRED , ZANDER NORBERT , FRANK RONALD , EICHNER WOLFRAM
IPC分类号： A61K8/73 , A61K9/00 , A61K9/14 , A61K38/00 , A61K38/18 , A61K47/48 , C07K14/505 , C07K14/53 , C07K14/54 , C07K14/55 , C07K14/56 , C07K14/565 , C07K17/06 , C07K17/10 , C08B31/00 , C08B31/08 , C08B31/12 , C08B33/04 , C08B35/04 , C12N15/12 , C07K , C08B , C12N , A61K
摘要： Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch at its reducing end with amino compound. The reducing end is not oxidized prior to the reaction. Preparation of hydroxyalkyl starch derivatives involves reaction of hydroxyalkyl starch of formula (I) at its reducing end with amino compound of formula R a-NH-R b (II). [Image] R 1-R 3H, linear or branched hydroxyalkyl; R aat least one functional group X capable of reacting with at least one other compound prior to or after the reaction; R ba functional group X or W; W : -NH-, -NH-C(=G)-, -NH-C(=G)-G-, -NH-S(O) 2- or -NH-C(=G)-NH-; X : -SH, -NH 2, -O-NH 2, -NH-O-alkyl, -C(=G)-NH-NH 2, -G-C(=G)-NH-NH 2, -NH-C(=G)-NH-NH 2 or -S(O) 2-NH-NH 2; and G : O or S. An independent claim is included for a pharmaceutical composition comprising the hydroxyalkyl starch derivative (where the reaction product of (I) with (II) is reacted via the functional group X in (II) with the further compound (III) or (II) is reacted via the functional group X with (III) prior to the reaction with (I), and the reaction product of (I) and (II) with the crosslinking compound is reacted with a polypeptide). ACTIVITY : Antianemic. Hydroxyethyl starch-erythropoietin (HES-EPO) was tested by the EPO-bioassay in normocythaemic mouse system and showed specific activity of 344000 U/mg, which was 3 fold higher than international BRP-erythropoietin reference standard preparation. MECHANISM OF ACTION : None given.

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