Blood-coagulation-promoting preparation based on human proteins and a method of producing the same
AssigneeImmuno Aktiengesellschaft fur chemisch-medizinische Produkte
InventorsJohann Eibl, Otto Schwarz, Fritz Elsinger, Anton Philapitsch
Life of this patent
Estimating the term…
Abstract
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.
Claims14
A blood-coagulation-promoting preparation based on human proteins, having a content of coagulation factors II, VII, IX and X and factor-VIII-inhibitor-by-passing-activity (FEIBA), which preparation is characterized in that
- it is free of thrombogenic activity up to at least 2 units of FEIBA per kg rabbit in the thrombosis inducing activity test according to Wessler,
- it is free of kallikrein activity and free of prekallikrein activator activity, measured in an aqueous solution of said preparation with a FEIBA concentration of up to at least 10 units per ml,
- it is affinity-chromatographically separable on dextran sulphate agarose by means of an NaCl gradient so as to obtain an eluate containing a protein with factor IX activity and an eluate containing a protein with FEIB-activity, said protein with factor IX activity eluting at a lower NaCl concentration than said protein with FEIB-activity,
- said eluate containing said protein with factor IX activity and said eluate containing said protein with FEIB-activity contain .alpha.- and .beta.-globulins when electrophoretically separated thus obtaining a separation curve having a main peak in the .alpha.-globulin region corresponding to a content of 60 to 80% of the total protein, a shoulder of 10 to 20% of the total protein following thereupon, and a slightly pronounced peak in the .beta.-globulin region corresponding to a content of 10 to 20% of the total protein following upon the shoulder-like course of said separation curve.
A blood-coagulation-promoting preparation based on human proteins, having a content of coagulation factors II, VII, IX and X and a factor-VIII-inhibitor-by-passing-activity (FEIBA), which preparation is characterized in that it is free of thrombogenic activity up to at least 2 units of FEIBA per kg rabbit in the thrombosis inducing activity test according to Wessler;
- it is free of kallikrein activity and free of prekallikrein activator activity, measured in an aqueous solution of said preparation with a FEIBA concentration of up to at least 10 units per ml;
- and it is affinity-chromatographically separable on dextran sulphate agarose by means of an NaCl gradient so as to obtain an eluate containing a protein with factor IX activity and an eluate containing a protein with FEIB-activity, said protein with factor IX activity eluting at a lower NaCl concentration than said protein with FEIB-activity.
A method for promoting the coagulation of blood containing an inhibitor to Factor VIII, which comprises administering to a patient having blood which contains an inhibitor to factor VIII, an amount, effective to provide factor-VIII-inhibitor-bypassing activity, of a blood coagulation-promoting preparation based on human proteins, having a content of coagulation factors II, VII, IX and X and factor-VIII-inhibitor-bypassing-activity (FEIBA), which preparation is characterized in that it is free of thrombogenic activity up to at least 2 units of FEIBA per kg rabbit in the thrombosis inducing activity test according to WEssler;
- it is free of kallikrein activity and free of prekallikrein activator activity, measured in an aqueous solution of said preparation with a FEIBA concentration of up to at least 10 units per ml;
- and it is affinity-chromatographically separable on dextran sulphate agarose by means of an NaCl gradient so as to obtain an eluate containing a protein with factor IX activity and an elute containing a protein with FEIB-activity, said protein with factor IX activity eluting at a lower NaCl concentration than said protein with FEIB-activity, said eluate containing said protein with factor IX activity and said eluate containing said protein with FEIB-activity contain .alpha.- and .beta.-globulins when electrophoretically separated thus obtaining a separation curve having a main peak in the .alpha.-globulin region corresponding to a content of 60 to 80% of the total protein, a shoulder of 10 to 20% of the total protein following thereupon, and a slightly pronounced peak in the .beta.-globulin region corresponding to a content of 10 to 20% of the total protein following upon the shoulderlike course of said separation curve.
A method for promoting the coagulation of blood containing an inhibitor to factor VIII, which comprises administering to a patient having blood which contains an inhibitor to factor VIII, an amount, effective to provide factor-VIII-inhibitor-bypassing-activity, of a blood coagulation-promoting preparation based on human proteins, having a content of coagulation factors II, VII, IX and X and factor-VIII-inhibitor-by-passing-activity (FEIBA), which preparation is characterized in that it is free of thrombogenic activity up to at least 2 units of FEIBA per kg rabbit in the thrombosis inducing activity test according to Wessler;
- it is free of kallikrein activity and free of prekallikrein activator activity, measured in an aqueous solution of said preparation with a FEIBA concentration of up to at least 10 units per ml;
- and it is affinity-chromatographically separable on dextran sulphate agarose by means of a NaCl gradient so as to obtain an eluate containing a protein with factor IX activity and an elute containing a protein with FEIB-activity, said protein with factor IX activity eluting at a lower NaCl concentration than said protein with FEIB-activity.
Dependencies are inferred from the claim text.