Immuno Aktiengesellschaft Fur Chemisch-medizinische Produkte

Immuno Aktiengesellschaft

Immuno Aktiengesellschaft Fur Chemisch-medizinisch Produkte

Otto Schwarz

Yendra Linnau

Johann J Eibl

Thomas Seelich

Anton Philapitsch

Fritz Elsinger

Franz Loblich

Gunter Wober

Friedrich Dorner

Karl Trambauer

Wolfgang Frechinger

Peter Turecek

Herbert Gritsch

Martha Eibl

Gunther Wober

Friedrich Elsinger

The invention relates to a method of producing virus-safe highly purified factor VIII. The method includes a combination of the following measures:

Method of producing a factor VIII preparation

There is disclosed a method of determining the presence of incompatibility-reaction-causing substances in blood products. There is also disclosed a method of inactivating incompatibility-reaction-causing substances in blood products to be applied therapeutically and prophylactically. For this purpose, a fraction obtained from human or animal blood is treated with pancreas enzymes bound to water insoluble carrier material and, optionally, the fraction is subjected to further fractionation and concentration.

Method of determining incompatibility-reaction-causing substances in

An immunoglobulin-G-containing fraction from human or animal plasma comprising monomeric IgG molecules as well as at least 70% gammaglobulins, destined for intravenous application. The fraction has a low anticomplementary activity and is substantially free of vasoactive and leucopenically active as well as bronchospastic substances.

Immunoglobulin-G-containing fraction

There is disclosed a method of inactivating reproducible filterable pathogens in blood plasma products by applying elevated temperatures. The blood plasma products are heat treated in a solid state in a closed inactivation container in the presence of specific amounts of water and organic compounds, provided that the water substantially remains physically bound to the blood plasma products, while the organic compound is present in a gaseous form in the atmosphere. The water content of the blood plasma products is 0.08 to 0.40. The concentration of the organic compounds in the gaseous phase is 0.01 to 10 g per liter of container volume.

Method of inactivating reproducible filterable pathogens in blood plasma

There is disclosed a method of producing a Factor VIII (AHF) containing fraction having a specific activity of at least 2.5 units of Factor VIII/mg protein as well as a portion of immunoglobulin G (IgG) of 10 mg/1000 units of Factor VIII at the most. Its risk of transmission of viral or bacterial infections is to be avoided or largely reduced. The method consists in that undesired proteins are at first precipitated from a Factor VIII (AHF) containing plasma fraction in the presence of SPS. The purified Factor VIII containing solution is treated with suitable salts or salt mixtures in order to obtain a Factor VIII containing precipitate. This precipitate is dissolved, lyophilized and finally heat-treated.

Method of producing a factor VIII (AHF) containing fraction

There is described a method of inactivating reproducible pathogens in preparations containing plasmatic enzymes and proenzymes, activated or non-activated coagulation factors, such as Factors II, V, VII, VIII, IX, X, XIII, 'FEIBA', prothrombin complex preparations, plasmatic inhibitors, immunoglobulins or other blood products, such as fibronectin and fibrinogen. In order to break and overcome the protective effect of proteins on pathogens by simultaneously preserving the biological activity and the molecular integrity of the proteins, the preparation is adjusted to a salt concentration of more than 0.5 molar by the addition of ammonium sulfate and is thermally treated, whereupon the ammonium sulfate is removed from the preparation.

Method of inactivating reproducible pathogens

A method of inactivating viruses in blood products is described, wherein the blood products are heat-treated in a humid or in a solid state in the presence of inorganic or organic hydroxyl group-containing compounds having an H.sup.+ -dissociation constant of &lt;10.sup.-11 in a concentration of more than 0.05 (5% by weight) and less than 0.70 (70% by weight). The hydroxyl group-containing compounds may be water, methanol, ethanol or mannitol. The temperature may amount up to 121.degree. C., the heat treatment may last from 1 s to 100 h. The inactivation method may be applied for producing blood products selected from enzymes, proenzymes including coagulation factors, enzyme inhibitors, immunoglobulins, albumin, plasminogen, fibrinogen, fibronectin or plasma, the inactivation destroying any reproducible filterable pathogens that might be present.

Method of inactivating reproducible filterable pathogens in blood

There is described a method for producing a preparation having a high content of Factor VIII (AHF), i.e. with a specific activity of at least 1.5 units of Factor VIII/mg protein, immunoglobulin G (IgG) of from 15 to 30 mg/1000 units of Factor VIII and fibrinogen of from 20 to 40 mg/100 units of Factor VIII. The method consists in that a Factor VIII containing plasma fraction is dissolved in a buffer, the solution is purified from undesired proteins by precipitation and is concentrated, the precipitation of undesired proteins being carried out in the presence of sulfated polysaccharide at a pH of from 6 to 7. After separation of the undesired proteins, a Factor VIII concentrate is precipitated, dissolved and processed into stable form. If desired, an antithrombin III-heparin complex or an antithrombin III-heparinoid complex is added to the solution.

Method for producing a preparation containing factor VIII (AHF)

A tissue adhesive on the basis of human or animal protein contains factor XIII and at least 33% by weight of fibrinogen, has a ratio of factor XIII to fibrinogen, expressed in units of factor XIII per gram of fibrinogen, of at least 80, contains fibrinogen and albumin in the total protein at a ratio of 33 to 90:5 to 40, contains plasminogen-activator-inhibitor or plasmin inhibitor in an amount of 250 to 25,000 KIU per g of fibrinogen and has been lyophilized.

Tissue adhesive

In a method of producing a factor-VIII(AHF)-high-concentrate having a specific activity of at least 2.5 units AHF and a fibrinogen content of less than 0.25 mg/mg protein from human or animal plasma, the plasma is subjected to a multi-step fractionation. The fraction purified by these fractionation measures and enriched in factor VIII (AHF) is subjected to a cryoalcohol precipitation and the resulting precipitate is processed into a stable form.

Method of producing a factor-VIII(AHF)-high-concentrate

In a method of producing a blood-coagulation-promoting preparation based on human proteins and having a content of coagulation factors II, VII, IX and X and factor-VIII-inhibitor-bypassing-activity (FEIBA), human plasma is treated with sulphated high-polymer carbohydrates and/or with basic ion exchangers, the protein mixture with generated FEIB-activity is adsorbed on the ion exchanger, and the preparation is gained by elution and concentration.

Blood-coagulation-promoting preparation based on human proteins and a

This invention relates to a tissue adhesive used in mammals for among other things to connect tissue or organs, in sealing wounds, stopping bleeding and healing wounds. The adhesive comprises specified amounts of factor XIII, fibrinogen, cold-insoluble globulin and albumin and plasminogen-activator inhibitor or plasmin inhibitor.

A tissue adhesive on the basis of human or animal proteins has a content of factor XIII and fibrinogen, the ratio of factor XIII to fibrinogen, expressed in units of factor XIII per gram of fibrinogen, amounting to at least 80. Furthermore, it contains a plasminogen-activator-inhibitor or plasmin-inhibitor in an amount of 20 to 2,000 KIU per ml.

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Vienna, Austria

Otto Schwarz