Albumin-purification method comprising a nanofiltration step, solution, and composition for therapeutic use containing the same

Abstract

The invention relates to an albumin-purification method comprising a step consisting in subjecting an aqueous albumin solution, with a concentration of between 15 g/l and 80 g/l and a pH of not less than 7, to nanofiltration in a temperature range of between 15 DEG C. and 55 DEG C. The invention also relates to: a virally-safe aqueous albumin solution which can be obtained using the invention method and in which the sites for the transport and binding of the active therapeutic ingredients of the albumin are available; and an albumin composition for therapeutic use, which is obtained by adapting the albumin solution that is intended for clinical use.

1 . A method for purifying albumin comprising a step of submitting an aqueous albumin solution, with a concentration of 15 g/L to 80 g/L and a pH not lower than 7, to a nanofiltration in a temperature range of 15° C. to 55° C.  
   
   
       2 . A method according to  claim 1 , characterised in that the nanofiltration is carried out on qualified filters having porosities of at least 13 nm.  
   
   
       3 . A method according to one of claims  1  and  2 , characterised in that the pH of the aqueous albumin solution is in the range of 7.8 to 11.5, and preferably, of 9 to 10.5.  
   
   
       4 . A method according to  claim 1 , characterised in that it further comprises a step of adding a pharmaceutically acceptable salt or salt mixture to the aqueous albumin solution to provide a solution with a ionic strength in the range of 0.01 to 0.55.  
   
   
       5 . A method according to  claim 4 , characterised in that the pharmaceutically acceptable salt is a salt of an alkali metal.  
   
   
       6 . A method according to  claim 5 , characterised in that the salt of an alkali metal is sodium chloride present in an amount imparting to the albumin solution an ionic strength of 0.15.  
   
   
       7 . A method according to  claim 1 , characterised in that the concentration of the aqueous albumin solution is in the range of 40 g/L to 60 g/L.  
   
   
       8 . A method according to  claim 1 , characterised in that the temperature of the aqueous albumin solution is between 30° C. and 55° C.  
   
   
       9 . A method according to  claim 1 , characterised in that the nanofiltration of the aqueous albumin solution is carried out in two successive steps on two filters with decreasing porosities, respectively.  
   
   
       10 . A method according to  claim 9 , characterised in that the two successive nanofiltration steps are carried out on filters with porosities of 23 to 50 nm and 15 or 20 nm, respectively.  
   
   
       11 . A method according to  claim 1 , characterised in that it is implemented with regenerated cellulose filters of 15 nm having a surface area of 0,01 m 2 , at a pressure not exceeding 1 bar.  
   
   
       12 . A method according to  claim 11 , characterised in that the pressure is in the range of 0.2 to 0.8 bar.  
   
   
       13 . A method according to  claim 1 , characterised in that the albumin is obtained by ethanol extraction and by purification by ion-exchange or affinity chromatography.  
   
   
       14 . A method according to  claim 1 , characterised in that it comprises a subsequent step of processing the aqueous albumin solution to make it suitable to a therapeutic use.  
   
   
       15 . A virally safe aqueous albumin solution obtainable by implementing the method according to  claim 1 , in which the transport and binding sites of therapeutically active ingredients are available in the albumin.  
   
   
       16 . An aqueous albumin solution according to  claim 15 , characterised in that it contains at most 1% albumin polymers with a size smaller than 100 nm.  
   
   
       17 . An aqueous albumin solution according to  claim 15 , characterised in that it contains at most 1% albumin polymers with a size smaller than 20 nm.  
   
   
       18 . An albumin composition for therapeutic use obtained by a process according to  claim 14 , for making an aqueous albumin solution, suitable to a clinical use.  
   
   
       19 . The use of an albumin composition for therapeutic use according to  claim 18 , for the stabilisation of at least one member selected from the group consisting of proteins in low concentrations and with high specific activities, specific immunoglobulins, monoclonal antibodies, vaccines, allergens, cytokines and peptidic hormones.  
   
   
       20 . The use according to  claim 19 , characterised in that the proteins are factor VIII or von Willebrand factor, and their recombinant equivalents.  
   
   
       21 . The use of an albumin composition for therapeutic use according to  claim 18 , for the transport and binding of therapeutically active ingredients.  
   
   
       22 . The use of an albumin composition for therapeutic use according to  claim 18 , as and excipient for an incubation medium for in-vitro fertilisation of human oocytes.  
   
   
       23 . The use of an albumin composition for therapeutic use according to  claim 18 , as a control standard protein.