Thrombus-targeted complexes of plasminogen activator and fibrin

Details Thrombus-targeted complexes of plasminogen activator and fibrin Thrombus-targeted complexes of plasminogen activator and fibrin

1991-11-25

1994-02-22

Stone, Jacqueline

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

424 943, 435219, 435226, 514 2, A61K 37547, A61K 3718

Patent

active

052884902

ABSTRACT:
Thrombolytic hybrids are formed as covalent or non-covalent complexes of fibrin fragments and plasminogen activator molecules. Native plasmin degradation fragments of fibrin or non-native fibrin fragments are covalently or non-covalently linked to plasminogen activators such as t-PA, scu-PA, urokinase, streptokinase, and the like. Useful native fibrin fragments which may be utilized to form complexes with plasminogen activators include fragments E.sub.1, E.sub.2, E.sub.3, D and DD, and (DD)E complex. The fibrin fragment component targets the hybrid to vascular thrombi, immobilizing the plasminogen activator molecule onto the fibrin surface of the thrombus. Once localized on a thrombus surface, the plasminogen activator component of the hybrid activates only the clot-surface bound plasminogen transported by the fibrin fragment vehicle, without significant systemic activation of plasminogen. The hybrids are strong potentiators of plasminogen activator activity, generating more plasmin from fibrin-surface bound plasminogen than the plasminogen activator molecule alone. The hybrids have a longer half-life in circulation than the corresponding unprotected plasminogen activator molecules.

REFERENCES:
patent: 4427646 (1984-01-01), Olexa et al.
patent: 4536391 (1985-08-01), Miyazaki et al.
patent: 4564596 (1986-01-01), Maximenko et al.
patent: 4673573 (1987-06-01), Ferres et al.
Bode et al., Science 229:765-767 (1985).
Bode et al., J. Biol. Chem. 262:10819-10823 (1987).
Bode et al., J. Mol. Cell Cardiol. 19:335-341 (1987).
de Munk et al, Biochemistry (1989) 28 7318-7325.
Takada et al, Biol. Abstracts vol. 86(7), Oct. 1988, No. 66184.
Takada et al., "Enhanced Activator Activity of the Mixture of Streptokinase and a Modified Form of PLasminogen (Lys-Plasminogen) in the Presence of Fibrin: Role of Conformational Change of Plasminogen" Haemostasis 18, 106 112 (1988).
Olexa et al., Proc. Natl. Acad. Sci. USA 77: 1374-1378 (1980).
Knight et al., J. Clin. Invest. 72:2007-2013 (1983).
Knight et al., Radiology 156:506-514 (1985).
Nieuwenhuizen et al., Biochem. Biophys. Acta 755:531-533 (1983).
Lijnen et al., Eur. J. Biochem. 144:541-544 (1984).
Nieuwenhuizen et al., Biochem. Biophys. Acta 748:86-92 (1983).

Affiliated with

Also associated with

Rating

Thrombus-targeted complexes of plasminogen activator and fibrin does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Thrombus-targeted complexes of plasminogen activator and fibrin , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Thrombus-targeted complexes of plasminogen activator and fibrin will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-169320