Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving blood clotting factor
Patent
1994-10-05
1996-08-20
Gitomer, Ralph J.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving blood clotting factor
435 23, 436 34, 436 69, C12Q 156, C12Q 137, G01N 3300
Patent
active
055478506
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The invention relates to a process for determining hirudin and synthetic thrombin inhibitors in the blood and a preparation for implementing the process.
Hirudin, which is obtained from the salivary gland of the Hirudo medicinalis (leech), is an anticoagulant, whose effect is based on the formation of a chemical compound with thrombin, whereby its catalytic action is inhibited. Hirudin is a miniprotein comprising 65 amino acids with a molecular weight of 7 kD. Owing to its strong affinity for thrombin (k.sub.1 values of 10.sup.- mol/l) and its direct mechanism of action, it is of great interest. Its clinical application was extremely limited in the past, since hirudin was not easily accessible in the standardized form. Today hirudin can be produced through genetic engineering; and, therefore, its clinical application can be expected in the near future.
For example, pharmaceutical preparations for oral administration are described in the EP-A-0 468 327; said preparations contain recombinant hirudin.
Recently hirudin has been intensively investigated pharmacologically; and the pharmacological data were acquired from experimental animals and humans. Hirudin is not metabolized in the liver, but rather eliminated in an unchanged form through the kidneys. Hirudin has an elimination half-life of about 1 to 2 hours and is distributed into the extracellular fluid spaces of the body. Analogous to heparin, hirudin is not resorbed orally. Past investigations have demonstrated that hirudin is active in almost all models of thrombosis, thus even during endotoxic shock and during experimental cardiac infarction and during prevention of reocclusion following thrombolysis. No immunological reactions were detected in the clinical-pharmacological investigations. During clinical investigations hirudin has proven to be superior to heparin as an anticoagulant and antithrombotic agent.
Currently many research laboratories are working world-wide on synthesizing synthetic, especially small molecular, inhibitors. The synthetic thrombin inhibitors act in the same manner as hirudin. Investigations with derivatives of benzamidines, such as NAPAP (N.alpha.-(2-napthylsulforyl-glycyl)-D,L-amidinophenylalanine-piperidide) and with so called tripeptides have exhibited the most progress. All synthetic thrombin inhibitors are currently in preclinical research. Their effects can be equated qualitatively with those of hirudin. However, the metabolism of the synthetic thrombin inhibitors differs from that of hirudin. Usually the thrombin inhibitors are metabolized in the liver or in the blood. It is anticipated that such substances will be available soon for clinical testing. The advantage over hirudin lies in the fact that the compounds can be administered orally.
However, for proper therapy or prophylaxis it is necessary that the hirudin content and the synthetic thrombin inhibitor content in the blood can be determined continuously, in order to avoid underdosing or to prevent side effects due to overdosing. In other words, therapeutic drug monitoring must be available. To date there exists no process for determining hirudin and synthetic thrombin inhibitors, especially in the blood, that can be implemented in a simple manner.
The present invention is based on the problem of providing a process for determining hirudin and synthetic thrombin inhibitors, especially in the blood, that can be applied extensively in a simple manner in hospitals, medical practices and laboratories and, for example, at the preoperative examination for diagnosing the risk of bleeding or thrombosis, for monitoring the anticoagulant therapy in thrombosis-endangered patients and at the followup of numerous diseases, for example severe infections, liver function damages and malignant diseases.
The process of the invention is supposed to be easy to implement, during which process devices can be used that already exist in hospitals and medical practices. In addition, a preparation for implementing the process shall be made available.
SUMMARY
REFERENCES:
patent: 4334018 (1982-06-01), Kirchhof
patent: 4379142 (1983-04-01), Port
patent: 5187102 (1993-02-01), Stocker
patent: 5192689 (1993-03-01), Hemker
Rhee M., Role of Meizothrombin and Meizothrombin (DESFI) . . . Biochem 1982 21 pp. 3437-3443.
Tijburg P., Formation of Meizothrombin . . . J of Biol Chem 266 (6) 1991 p. 4017-4022.
Chemical Abstract 87 (1977): 19602b; Latallo, Z. S.; Teisseyre, E., Proc. Symp. Dtsch. Ges. Klin.
Chem Abstract vol. 98: 13567p 1983 Briet E.
Chemical Abstracts 102 (1985): 125309p; Green, D.; et al.; Thromb. Res. 1985, 37 (1), 145-53.
Bucha Elke
Hoffman Jutta
Nowak Gotz
Gitomer Ralph J.
Max-Planck-Gesellschaft
LandOfFree
Process for determining hirudin and synthetic thrombin inhibitor does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for determining hirudin and synthetic thrombin inhibitor, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for determining hirudin and synthetic thrombin inhibitor will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2330083