公开(公告)号：WO2023017020A1

公开(公告)日：2023-02-16

申请号：PCT/EP2022/072325

申请日：2022-08-09

申请人： GRIFOLS WORLDWIDE OPERATIONS LIMITED

发明人： GRANCHA GAMON, Salvador ,  FARO TOMAS, Maria Mercedes ,  MARTINEZ CREUS, Nuria

IPC分类号： A61K38/37 ,  A61K9/00 ,  A61K9/19 ,  A61K47/18 ,  A61P7/04

摘要： The present invention refers to a new method for producing a lyophilized pharmaceutical composition comprising human plasma-derived Factor Vlll/Von Willebrand Factor (FVIII/VWF) complex, comprising the steps of: a) providing an initial aqueous solution comprising FVIII/VWF with at least (90) III of FVIII per mg of total proteins, with a ratio of VWF/FVIII activity of at least 0.7; b) adding arginine, histidine, and human serum albumin (HAS); c) lyophilizing the FVIII/VWF solution obtained in step b); and d) reconstituting the lyophilized FVIII/VWF in water for injection thereby obtaining a therapeutic product adequate for the treatment of Hemophilia A and Von Willebrand Disease, wherein prior to administration to a patient, arginine is at a concentration between (42) and (98) mmol/L, histidine is at a concentration between (10) and (24) mmol/L, and albumin is at a concentration between (1) and (2.5) % (w/v), FVIII potency and VWF potency are equal to or higher than 200 ILI/mL, and the obtained product has a FVIII dose up to 3600 lU/vial and a VWF dose up to 5040 lll/vial.