Enzyme derivatives for use in the treatment of venous thrombosis
AssigneeBeecham Group Limited
InventorRichard A. G. Smith
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Abstract
A pharmaceutical composition which comprises a pharmaceutically acceptable carrier together with an in vivo fibrinolytic enzyme as defined herein wherein the catalytic site essential for fibrinolytic activity is blocked by a group which is removable by hydrolysis at a rate such that the pseudo-first order rate constant for hydrolysis is in the range 10.sup.-6 sec.sup.-1 to 10.sup.-3 sec.sup.-1 in isotonic aqueous media at pH 7.4 at 37.degree. C.; is useful in the treatment of venous thrombosis.
Claims28
A pharmaceutical composition for treatment of Venous thrombosis which comprises a pharmaceutically acceptable carrier together with an in vivo fibrinolytic enzyme as defined herein wherein the catalytic site essential for fibrinolytic activity is blocked by a group which is removable by hydrolysis at a rate such that the pseudo-first order rate constant for hydrolysis is in the range 10.sup.-6 sec.sup.-1 to 10.sup.-3 sec.sup.-1 in isotonic aqueous media at pH 7.4 at 37.degree. C.
A derivative of an in vivo fibrinolytic enzyme as defined herein wherein the catalytic site essential for fibrinolytic activity is blocked by a group which is removable by hydrolysis such that the pseudo-first order rate constant for hydrolysis of the derivative is in the range 10.sup.-6 sec.sup.-1 to 10.sup.-3 sec.sup.-1 in isotonic aqueous media at pH 7.4 at 37.degree. C. with the exception of:
- (1) p-guanidinobenzoyl human plasmin,
- (2) p-guanidinobenzoyl streptokinase-plasminogen activator complex.
A derivative as claimed in claim 19 wherein the acyl group is a benzoyl group or a substituted benzoyl group having one or more meta and/or para substituents wherein the sum of the Hammett .sigma..sub.m or .sigma..sub.p values is in the range +0.1 to -1.1.
p-Anisoyl human plasmin.
p-Anisoyl streptokinase human plasminogen activator complex.
A mixture of p-anisoyl human plasmin and p-anisoyl streptokinase human plasminogen activator complex.
Dependencies are inferred from the claim text.