Plasminogen activator derivatives
AssigneeNippon Chemiphar Co., Ltd.
InventorsKimihiro Shimizu, Tsuguji Nakahara, Taketoshi Kinoshita, Jun Takatsuka, Michiko Igarashi
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Abstract
Derivatives of a nonimmunogenic plasminogen activator which comprises at least one polyalkylene glycol group chemically bonded with at least one coupling agent to amino acid side chains of said plasminogen activator, wherein said polyalkylene glycol has a molecular weight of about 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof. The plasminogen activator derivatives have an extended circulating life in the mammalian bloodstream and also inhibit the formation of thrombus in the same.
Claims24
A derivative of a nonimmunogenic human plasminogen activator, comprising at least one polyalkylene glycol chemically bonded with at least one coupling agent to the amino acid side chains of said plasminogen activator, wherein said polyalkylene glycol has a molecular weight in the range of 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof.
Monomethyl ether polyethylene glycol-4,6-dichloro-1,3,5-triazine-modified urokinase, whose polyethylene glycol moiety has an average molecular weight of about 5,000.
Polypropylene glycol-4-chloro-6-hydroxy-1,3,5-triazine-modified urokinase, whose polypropylene glycol moiety has an average molecular weight of about 4,000.
A process for preparing a derivative of a nonimmunogenic human plasminogen activator, which comprises reacting a coupled product of at least one polyalkylene glycol and at least one coupling agent with a plasminogen activator, wherein said polyalkylene glycol has a molecular weight in the range of 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof.
A method of extending the circulating life of a human plasminogen activator in a mammalian bloodstream which comprises chemically modifying said plasminogen activator by bonding at least one polyalkylene glycol moiety having a molecular weight of between about 200 and 20,000, thereto by means of a coupling agent to the amino acid side chains of said plasminogen activator.
A method of inhibiting the formation of thrombus in a mammalian bloodstream which comprises administering to said mammals an effective amount of a nonimmunogenic human plasminogen activator comprising at least one polyalkylene glycol moiety chemically bonded with at least one coupling agent to the amino acid side chains of said plasminogen activator, wherein said polyalkylene glycol has a molecular weight in the range of 200-20,000 and is unsubstituted or is substituted with one or more alkyl, alkoxy or alkanoyl groups or a mixture thereof.
Dependencies are inferred from the claim text.