Removal of serine proteases by treatment with finely divided silicon dioxide

摘要

The present invention provides novel methods for reducing the serine protease and/or serine protease zymogen content of a plasma-derived protein composition. Also provided are methods for manufacturing plasma-derived protein compositions having reduced serine protease and/or serine protease zymogen content. Among yet other aspects, the present invention provides aqueous and lyophilized compositions of plasma-derived proteins having reduced serine protease and/or serine protease zymogen content. Yet other aspects include methods for treating, managing, and/or preventing a disease comprising the administration of a plasma-derived protein composition having a reduced serine protease or serine protease zymogen content.

主权项

1. A method for preparing an inter-alpha-trypsin inhibitor (IαI) composition having a reduced amount of a serine protease or a serine protease zymogen, the method comprising the steps of:
(a) contacting a blood-plasma derived solution containing IαI and at least one serine protease with from 0.01 grams to 10 grams finely divided silicon dioxide (SiO2) per gram protein under conditions suitable to bind the IαI and at least one serine protease, the conditions including a pH of from 4.0 to 7.0 and a conductivity of from 0.1 mS/cm to 2.0 mS/cm; (b) separating the SiO2 from the composition; (c) eluting the serine protease or serine protease zymogen from the SiO2 under conditions in which at least 50% of the IαI remains bound, the conditions including a pH of from 5.0 to 7.0 and a conductivity of less than 5 mS/cm; and (d) eluting the IαI from the SiO2 under conditions including a pH of from 7.0 to 8.0 and a conductivity of at least 2 mS/cm.