Stabilized protein preparation and process for its preparation

Abstract

A stabilized protein preparation is described which contains no antithrombin III and is protected against loss of activity during pasteurization by the addition of stabilizers which comprise one or more saccharides as a mixture with more than 0.5 mol/l of one or more amino acids chosen from the group arginine, lysine, histidine, phenylalanine, tryptophan, tyrosine, aspartic acid and its salts or glutamic acid and its salts. Glycine and/or glutamine can also be additionally added to each of these amino acids. A process for the viral inactivation or viral depletion of a protein preparation of this type which contains the abovementioned stabilizers and is subjected to pasteurization or viral depletion by filtration, centrifugation or treatment with detergents or bactericidal or virucidal agents is also described.

We claim:  
     
         1 . A stabilized protein preparation, which is protected against a loss of activity during pasteurization by the addition of stabilizers which comprise one or more saccharides as a mixture with more than 0.5 mol/l of one or more amino acids chosen from arginine, lysine, histidine, phenylalanine, tryptophan, tyrosine, aspartic acid and its salts, and glutamic acid and its salts, and wherein the stabilized protein preparation contains no antithrombin III.  
     
     
         2 . The stabilized protein preparation as claimed in  claim 1 , wherein the protein is one or more blood clotting factors chosen from FII, FV, FVII and FVIIa, FVIII, FIX, FX, FXII and their combination preparations, the von Willebrand factor (vWF), FVIII/vWF, or one or more proteins chosen from albumins, immunoglobulins, protease inhibitors, ∝-2-antiplasmin, ∝-1-antitrypsin, protein C, activated protein C, protein S, protein Z, tissue factor pathway inhibitor (TFPI), fibrinogen, fibronectin and plasminogen.  
     
     
         3 . The stabilized protein preparation as claimed in  claim 1 , wherein the saccharide is a monosaccharide, a disaccharide or an oligosaccharide present in an amount of at least 0.5 g/ml.  
     
     
         4 . The stabilized protein preparation as claimed in  claim 1 , wherein the saccharide is a monosaccharide, a disaccharide or an oligosaccharide present in an amount of at least 1.0 g/ml.  
     
     
         5 . The stabilized protein preparation as claimed in  claim 1 , wherein the saccharide is is a monosaccharide, a disaccharide or an oligosaccharide present in an amount of more than 1.5 g/ml.  
     
     
         6 . The stabilized protein preparation as claimed in  claim 1 , wherein the one or more amino acids are present in an amount of more than 0.8 mol/l.  
     
     
         7 . The stabilized protein preparation as claimed in  claim 1 , wherein the preparation further comprises a soluble calcium salt in an amount of at least 0.5 mmol/l.  
     
     
         8 . The stabilized protein preparation according to  claim 1 , wherein the preparation further comprises glycine, glutamine, or glycine and glutamine together.  
     
     
         9 . The stabilized protein preparation according to  claim 1 , wherein the preparation further comprises a soluble calcium salt in an amount of at least 1.0 mmol/l.  
     
     
         10 . A process for the viral inactivation or viral depletion of a protein preparation, which comprises subjecting a stabilized protein preparation as claimed in  claim 1  to a heat treatment at 40 to 95° C. for a period of 5 to 50 hours.  
     
     
         11 . A process for the viral inactivation or viral depletion of a protein preparation, which comprises subjecting a stabilized protein preparation as claimed in  claim 1  to viral depletion by means of filtration.  
     
     
         12 . A process for the viral inactivation or viral depletion of a protein preparation, which comprises subjecting a stabilized protein preparation as claimed in  claim 1  to a viral depletion by means of centrifugation.  
     
     
         13 . A process for the viral inactivation or viral depletion of a protein preparation, which comprises subjecting a stabilized protein preparation as claimed in  claim 1  to a treatment with detergents or bactericidal or virucidal agents.  
     
     
         14 . A stabilized protein preparation, which is protected against loss of activity during pasteurization by the addition of stabilizers which comprise more than 1.5 g/ml of one or more saccharides as a mixture with more than 0.8 mol/l of one or more amino acids chosen from arginine, lysine, histidine, phenylalanine, tryptophan, tyrosine, aspartic acid and its salts, and glutamic acid and its salts, and wherein the stabilized protein preparation contains no antithrombin III.  
     
     
         15 . The stabilized protein preparation as claimed in  claim 14 , wherein the preparation further comprises glycine, glutamine, or glycine and glutamine together.  
     
     
         16 . The stabilized protein preparation as claimed in  claim 14 , wherein the preparation further comprises a soluble calcium salt in an amount of at least 0.5 mmol/l.