Aqueous formulation comprising at least a neutral salt and a biopharmaceutical protein

Abstract

The present invention is related to a pharmaceutically acceptable aqueous formulation comprising at least a neutral salt and a biopharmaceutical protein, wherein the concentration ratio between the biopharmaceutical protein and the neutral salt is in the range of ≧0.7 and ≦5.

1 . A pharmaceutieally acceptable aqueous formulation comprising at least a neutral salt and a biopharmaceutical protein, wherein the concentration ratio between the biopharmaceutical protein and the neutral salt is in the range of ≧0.7 and ≦5. 
     
     
         2 . The formulation according to  claim 1 , wherein the biopharmaceutical protein has between ≧150 and ≦220 amino acid residues and/or a molecular weight between ≧15 and ≦26 kDaltons. 
     
     
         3 . The formulation according to  claim 1 , wherein the biopharmaceutical protein is human growth hormone (hGH). 
     
     
         4 . The formulation according to  claim 1 , wherein said formulation further comprises at least one agent selected from the group consisting of
 a buffer,   a non-ionic surfactant,   a tonifier, and/or   a preservative.   
     
     
         5 . The formulation according to  claim 4 , wherein said buffer is selected from the group consisting of:
 Phosphate buffer (Na 3 PO 4 , NaH 2 PO 4  and/or Na 2 HPO 4 ),   Citrate,   Tris,   Succinate,   Acetate, and/or   Histidine.   
     
     
         6 . The formulation according to  claim 4 , wherein said non-ionic surfactant is selected from the group consisting of:
 Poloxamer, preferably Poloxamer 188 or Poloxamer 184,   Pluronic F-68, and/or   Polysorbate, preferably Polysorbate 20 or Polysorbate 80.   
     
     
         7 . The formulation according to  claim 4 , wherein said tonifier is selected from the group consisting of:
 Mannitol,   Glycine, and/or   Sorbitol.   
     
     
         8 . The formulation according to  claim 4 , wherein said preservative is selected from the group consisting of:
 Phenol,   meta-cresol,   methyl paraben,   propyl paraben,   benzalconium chloride,   benzethonium chloride, and/or   Benzyl Alcohol.   
     
     
         9 . The formulation according to  claim 3 , wherein human growth hormone (hGH) is present in a concentration ranging between ≧3 and ≦20 mg ml −1 . 
     
     
         10 . The formulation according to  claim 1 , wherein said neutral salt is
 Sodium Chloride (NaCl).   
     
     
         11 . The formulation according to  claim 1 , wherein said neutral salt is present in a concentration ranging between ≧2 and ≦100 mg ml −1 . 
     
     
         12 . The formulation according to  claim 1 , wherein the pH of said formulation is in a range between ≧5.8 and ≦6.2 
     
     
         13 . The formulation according to  claim 1 , wherein said formulation has an optimized stability. 
     
     
         14 . A method of increasing the stability of a pharmaceutically acceptable aqueous formulation comprising a biopharmaceutical protein, which method comprises providing the biopharmaceutical protein and the neutral salt in a final concentration ration in the range of ≧0.7 and ≦5. 
     
     
         15 . The method of  claim 14 , wherein the biopharmaceutical protein is human growth hormone (hGH). 
     
     
         16 . Use of a formulation according to  claim 14 , for the treatment of at least one condition selected from the group consisting of
 Growth Hormone Deficiency,   small for gestational age (SGA) or intrauterine growth retardation (IUGR),   Idiopathic Short Stature,   AIDS Wasting and Cachexia,   Short Stature Caused by Turner's Syndrome,   Short Stature Caused by Prader-Willi Syndrome,   Growth Problems Caused by Short Bowel Syndrome,   Improper Growth in Children with Renal Disease,   Rheumatoid Arthritis,   Osteoporosis, and   X-Linked Hypophosphatemic Rickets.   
     
     
         17 . A primary packaging comprising the formulation according to  claim 1 .