Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-06-30
1996-03-19
Lilling, Herbert J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
435212, 435215, 435216, 435226, 424 9463, 424 9464, A61K 3800, A61K 3848
Patent
active
055004113
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The subject of the present invention is the use of thrombolytically active proteins for treating thromboembolic conditions, via multiple bolus administration.
The methodology employed inhibits the reocclusion rate in the subject so treated. Preferably, the thrombolytically active protein has a half life longer than that of recombinant t-PA
BACKGROUND AND PRIOR ART
Thrombolytic therapy of myocardial infarction is an effective, medically well tested and proved therapy for the removal of occlusive thrombi in the coronary arteries of the heart. Recombinant human t-PA (tissue-type plasminogen activator) produced by DNA technology is used in accordance with U.S. Pat. No. 4,766,075 has proven to be effective for the dissolution of coronary thrombi (Verstraete et al., Lancet II, 1985; 965-969). By early lysis therapy of the myocardial infarction the residual heart function after myocardial infarction can be improved in comparison with other therapies (Armstrong et al., J. Hm. Coll. Cardiol., 1989; 13: 1469-1476) and a higher survival rate can be achieved in comparison with other therapies (Wilcox et al., Lancet II, 1988; 525-539).
Large thrombolysis studies with, in all, several thousand patients show that rapid induction of thrombolysis with early reperfusion of the myocardial tissue leads to rescue of myocardial tissue and thus to an increase of survival rate (GISSI study group, Lancet I, 1986; 397-401). For this reason, it is necessary to induce thrombolytic therapy at a point of time at which the tissue lying behind the coronary occlusion is not yet irreversibly damaged.
In principle, in the case of the treatment of a coronary occlusion, the problem exists of avoiding reocclusion of the infarcted blood vessel after successful initial thrombolysis. This disadvantageous effect has been observed for recombinant t-PA (e.g., Alteplase) (Chesebro et al., Circulation, 1987; 76: 142-154). The reocclusion of the infarcted blood vessel leads to increased morbidity and mortality. For the prevention of reocclusions, substances are used of differing pharmacological working principles, such as heparin (Bleich et al., Am. J. Cardiol., 1990; 66: 1412-1417) and acetylsalicylic acid (Hsia et al., N. Engl. J. Med. 1990: 323: 1433-1437). The prolonged infusion of recombinant t-PA (Alteplase) is also said to prevent the reocclusion of the infarct blood vessel due to a longer period of thrombolysis (Gold et al., Circulation, 1986: 73: 347-352; Verstraete et al., Am. J. Cardiol. 1987; 60: 231-237; Johns et al., Circulation, 1988; 78: 546-556). However, after ending of the infusion, the appearance of reocclusions is frequently observed.
Human tissue plasminogen activator, produced by recombinant DNA technology ("rt-PA") has already been administered as double or multiple bolus to a few patients in the scope of clinical preliminary investigations. Admittedly, high dissolution rates of the thrombi were found up to 90 minutes after the administration of the first bolus but, because of the high doses, extensive, systemic plasminogen activation with subsequent almost complete reduction of fibrinogen was observed (only 15.5 to 5.2% of the initial value) (J. Am. Coll. Cardiol. 1991 (17(2), 152A). Undesired reduction of fibrinogen levels represents a disadvantage in that during emergency operations, since there is a high tendency to haemorrhage intensive supervision of the patient is necessary. Further, in the case of double and triple bolus administration of rt-PA, tendency to reocclude was observed in the blood vessels (Circulation, 1990, 82(4), Suppl. III, 538, abstract 2137; Br. J. Haematol. 1991, 77, Suppl. 1, 47, abstract P080). A study was also carried out for Alteplase in which multiple bolus administration was investigated in more detail (Coronary Artery Disease, 1990, 1(1), 83-88). The study concluded that single bolus administration was preferred.
Because of the above-mentioned disadvantageous effects, administration of rt-PA in the form of a double or multiple bolus has bound no practical use. Furthermo
REFERENCES:
patent: 4970159 (1990-11-01), Dodd
patent: 4980165 (1990-12-01), Isaacs et al.
patent: 5084274 (1992-01-01), Griffin et al.
patent: 5223256 (1993-06-01), Stern et al.
patent: 5234686 (1993-08-01), Dodd
patent: 5242688 (1993-09-01), Burck et al.
patent: 5350578 (1994-09-01), Griffin et al.
patent: 5352453 (1994-10-01), Kohnert et al.
patent: 5366730 (1994-11-01), Kohnert et al.
Klabunde et al "Thrombosis Res." 58:511-517 (1990).
Koenig Reinhard
Martin Ulrich
Boehringer Mannheim GmbH
Lilling Herbert J.
LandOfFree
Method for treating thromboembolic conditions by inhibiting reoc does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for treating thromboembolic conditions by inhibiting reoc, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for treating thromboembolic conditions by inhibiting reoc will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1959360