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WO1992020361A1 - Nouvelle combinaison de facteur viii et d'un antifibrinolytique - Google Patents

Nouvelle combinaison de facteur viii et d'un antifibrinolytique Download PDF

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Publication number
WO1992020361A1
WO1992020361A1 PCT/EP1992/000941 EP9200941W WO9220361A1 WO 1992020361 A1 WO1992020361 A1 WO 1992020361A1 EP 9200941 W EP9200941 W EP 9200941W WO 9220361 A1 WO9220361 A1 WO 9220361A1
Authority
WO
WIPO (PCT)
Prior art keywords
factor viii
antifibrinolytic
blood
substances
mixture
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP1992/000941
Other languages
German (de)
English (en)
Inventor
Verena Baldinger
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbott GmbH and Co KG
Original Assignee
Knoll GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Knoll GmbH filed Critical Knoll GmbH
Publication of WO1992020361A1 publication Critical patent/WO1992020361A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A61K38/095—Oxytocins; Vasopressins; Related peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36—Blood coagulation or fibrinolysis factors
    • A61K38/37—Factors VIII

Definitions

  • the present invention relates to a new active ingredient combination of the blood coagulation factor VIII or a substance that increases its concentration in the blood, and an antifibrinolyti um.
  • anticoagulants In the treatment of coronary heart diseases and for thrombosis prophylaxis in general, anticoagulants must be administered over a longer period of time. Patients who are treated with such substances are at risk of bleeding to death in the event of injuries because the blood's ability to clot is blocked or at least greatly reduced by the anticoagulants. Substances must therefore be available which are administered to patients treated with anticoagulants in the event of an injury, the need for surgery or in the event of an overdose and which eliminate or block the action of the anticoagulants. A 20 such substance should be available for each anticoagulant.
  • Coagulation and fibrinolysis are in dynamic equilibrium in every organism. If a patient is treated with anticoagulants, this balance is shifted in favor of fibrinolysis 5 and blood clotting is impeded.
  • Known anticoagulant substances are hirudin, heparin, low molecular weight heparins or synthetic thrombin inhibitors or hirudin derivatives. It has been described that, for example, the APTT-prolonging effect of hirudin can be partially abolished by applying factor VIII or fragments thereof (EP 367 713).
  • factor VIII, its fragments or substances which increase its concentration in the blood has the disadvantage, however, that this treatment causes the effects of hirudin only in very high doses and not immediately, but only with a fairly large time Delay and incomplete cancellation because the release of factor VIII reaches its maximum in humans only after 30 to 60 minutes. For acute emergencies, the sole administration of 0 factor VIII for hemostasis is insufficient. It has now been found that the coagulation-promoting effect of blood coagulation factors such as factor VIII or a substance which increases its concentration in the blood can be greatly improved by adding further substances.
  • the invention relates to a mixture of a) factor VIII, its active fragments and / or substances which cause the formation of factor VIII in the blood, and b) an antifibrinolytic.
  • Factor VIII is a long-known factor of B - coagulation, which is applied prophylactically in patients with haemophilia A or Von Willebrand disease (vascular pseudohemophilia A) and before minor surgical interventions such as tooth extraction (Nature 312, 337 (1984)).
  • Peptides whose sequences have homologies to factor VIII and which result from tryptic digestion of factor VIII or can be prepared synthetically and have factor VIII activity are suitable as active fragments of factor VIII.
  • Factor VIII can be found in the plasma in a concentration of 1 U / ml. To neutralize the anticoagulant effects which are achieved with the usual doses of anticoagulants, the high dose of 30 to 200 U / kg of body weight is required with factor VIII alone.
  • Desmopressin (Merck Index, 11th edition, No. 2904), adrenaline, ⁇ -vasopressin are described as substances which increase the concentration of factor VIII in the blood. However, all of these substances have other effects in the doses releasing factor VIII. For example, Desmopressin releases tPA, thereby increasing fibrinolytic activity. The tPA-releasing effect of desmopressin on humans reaches its maximum after only 20 min, the factor VIII releasing effect, however, only after 40 min (Thromb. Haem. 58, 366 (1987)).
  • Desmopressin is used to reduce blood clotting times in the case of prophylactic administration before minor surgical interventions, in order to effectively eliminate acute bleeding risks after anticoagulant therapy, Desmopressin or another antidote that works by increasing blood coagulation factors can be combined with an antifibrinolytic.
  • Aprotinin, tranexamic acid, ⁇ -aminocaproic acid and 4-aminomethylbenzoic acid are particularly suitable as antifibrinolytics.
  • the components a) and b) are incorporated into the mixture in the amounts in which they are normally administered as individual substances. These dosages are usually for
  • the mixture is usually administered intravenously.
  • the new combination of active ingredients can be used very well as an antidote against anticoagulants in the case of bleeding complications, overdosage of the anticoagulant and in preparation for operations on patients who are treated with anticoagulants. It has the advantage that its effect begins immediately after IV application and that the required doses of blood coagulation factor VIII or of substances which increase the concentration of factor VIII in the blood are considerably lower as a result of the combination.
  • synthetic thrombin inhibitors such as hirudin or hirudin derivatives
  • warfarin phenprocoumon and acenocoumarol.
  • the anti-oagulatory effect of hirudin and polyethylene glycol hirudin is particularly well inhibited.
  • rats were administered intravenously with 1 mg / kg of hirudin at the time.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Hematology (AREA)
  • Zoology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Un mélange de (a) facteur VIII, de ses fragments et/ou de substances qui provoquent la libération ou la formation de facteur VIII dans le sang, et de (b) un antifibrinolytique est utile comme antidote d'anticoagulants.
PCT/EP1992/000941 1991-05-11 1992-04-30 Nouvelle combinaison de facteur viii et d'un antifibrinolytique Ceased WO1992020361A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE4115453A DE4115453A1 (de) 1991-05-11 1991-05-11 Neue wirkstoffkombination
DEP4115453.3 1991-05-11

Publications (1)

Publication Number Publication Date
WO1992020361A1 true WO1992020361A1 (fr) 1992-11-26

Family

ID=6431488

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1992/000941 Ceased WO1992020361A1 (fr) 1991-05-11 1992-04-30 Nouvelle combinaison de facteur viii et d'un antifibrinolytique

Country Status (2)

Country Link
DE (1) DE4115453A1 (fr)
WO (1) WO1992020361A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0713881A2 (fr) 1994-10-20 1996-05-29 BEHRINGWERKE Aktiengesellschaft Utilisation de concentration contenant du vWF avec des agent antithrombotiques et fibrinolytiques dans la thérapie combinée
WO1998024474A1 (fr) * 1996-12-06 1998-06-11 Fonden Til Fremme Af Eksperimentel Cancerforskning Inhibition du remodelage invasif
US10980757B2 (en) 2018-09-06 2021-04-20 RTU Pharma SA Ready-to-use tranexamic acid intravenous solution

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4317282A1 (de) * 1993-05-25 1994-12-01 Behringwerke Ag Arzneimittel zur Behandlung der Sepsis und des septischen Schocks
AT409335B (de) * 1998-11-10 2002-07-25 Immuno Ag Pharmazeutisches präparat enthaltend einen rezeptor-antagonisten zur behandlung von blutgerinnungsstörungen
EP1190724B8 (fr) * 2000-09-22 2006-05-03 Perlei Medical Produkte GmbH Utilisation d'agents antifibrinolytique pour la préparation de tampons, compresses ou pansements

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2085729A (en) * 1980-10-17 1982-05-06 Dainippon Pharmaceutical Co Pharmaceutical composition for oral administration containing coagulation factor VIII

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2085729A (en) * 1980-10-17 1982-05-06 Dainippon Pharmaceutical Co Pharmaceutical composition for oral administration containing coagulation factor VIII

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Biological Abstracts, Band 68, Nr. 4, 1992, (Philadelphia, PA, US), I.M. NILSSON et al.: "Factor VIII concentrate prepared from DDAVP stimulated blood donor plasma", siehe Zusammenfassung Nr. 19931, & SCAND. J. HAEMATOL. 221(1), 42-46, 1979, siehe Zusammenfassung *
Biological Abstracts, Band 81, Nr. 6, 1986, (Philadelphia, PA, US), A.K. BURROUGHS et al.: "Desmopressin and bleeding time in patients with cirrhosis", siehe Seite AB-751, Zusammenfassung Nr. 55563, & BR. MED. J. 291(6506), 1377-1381, 1985, siehe Zusammenfassung *
Biological Abstracts, Band 83, Nr. 9, 1987, (Philadelphia, PA, US), S. SCHULMAN et al.: "DDAVP-induced correction of prolonged bleeding time in patients with congenital platelet function defects", siehe Seite AB-871, Zusammenfassung Nr. 89480, & THROMB. RES. 45(2), 165-174, 1987, siehe Zusammenfassung *
Dialog Embase, Dialog Nr. 1451927, Embase Nr. 79222355, I.M. NILSSON et al.: "DDAVP factor VIII concentrate and its properties in vivo and in vitro", & THROMB. RES. (USA), 1979, 15/1-2, 263-271, siehe Zusammenfassung *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0713881A2 (fr) 1994-10-20 1996-05-29 BEHRINGWERKE Aktiengesellschaft Utilisation de concentration contenant du vWF avec des agent antithrombotiques et fibrinolytiques dans la thérapie combinée
EP0713881A3 (fr) * 1994-10-20 1996-08-21 Behringwerke Ag Utilisation de concentration contenant du vWF avec des agent antithrombotiques et fibrinolytiques dans la thérapie combinée
US5571784A (en) * 1994-10-20 1996-11-05 Behringwerke Aktiengesellschaft Use of VWF-containing concentrates as a therapy which is employed in combination with antithrombotic and fibrinolytic therapy
WO1998024474A1 (fr) * 1996-12-06 1998-06-11 Fonden Til Fremme Af Eksperimentel Cancerforskning Inhibition du remodelage invasif
US10980757B2 (en) 2018-09-06 2021-04-20 RTU Pharma SA Ready-to-use tranexamic acid intravenous solution
US11696905B2 (en) 2018-09-06 2023-07-11 RTU Pharma SA Ready-to-use tranexamic acid intravenous solution

Also Published As

Publication number Publication date
DE4115453A1 (de) 1992-11-12

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