Aqueous solution of burlulipase comprising calcium ions

Abstract

The present invention relates to an aqueous solution comprising burlulipase which is characterized in that it contains calcium ions. In particular, it also relates to corresponding pharmaceuticals. Such pharmaceuticals are suitable for the treatment of exocrine pancreatic insufficiency. These pharmaceuticals are particularly suitable for treating patients having cystic fibrosis and in pediatrics. Another aspect of the present invention relates to container-packaged solutions and pharmaceuticals as mentioned above, which are containers produced by the blow-fill-seal method, and to methods for producing such packaged solutions and pharmaceuticals.

1 . A method of preparing a stabilized pharmaceutical preparation, comprising the steps of:
 combining pharmaceutical grade burlulipase with a pharmaceutically suitable source of calcium ions in an aqueous solution suitable for administration to a patient.   
     
     
         2 . The method according to  claim 1 , wherein:
 the concentration of calcium ions in the aqueous solution is 0.1 to 200 mmol/l.   
     
     
         3 . The method according to  claim 1 , wherein:
 the source of calcium ions is calcium chloride.   
     
     
         4 . The method according to  claim 3 , wherein:
 the aqueous solution comprises calcium chloride in a concentration of 0.1 to 200 mmol/l.   
     
     
         5 . The method according to  claim 3 , wherein:
 the concentration of calcium ions or calcium chloride in the aqueous solution is 0.2 to 100 mmol/l.   
     
     
         6 . The method according to  claim 1 , wherein:
 the concentration of burlulipase in the aqueous solution is at least one selected from the group of:
 0.1 to 35 mg per mL; 
 0.5 to 30 mg per mL; 
 1 to 25 mg per mL; and 
 3 to 20 mg per mL 
   
     
     
         7 . The method according to  claim 1 , wherein:
 the aqueous solution has a pH of 4 to 9.   
     
     
         8 . The method according to  claim 1 , further comprising the step of:
 adding tris(hydroxymethyl)aminomethane to the aqueous solution.   
     
     
         9 . The method according to  claim 1 , wherein the pharmaceutical grade burlulipase further comprises at least one of 6-deoxy-talane, lipids, and/or rhamnolipids. 
     
     
         10 . The method according to  claim 1 , further comprising the step of:
 adding one or more pharmaceutically acceptable excipients to the aqueous solution.   
     
     
         11 . The method according to  claim 1 , further comprising the step of:
 packaging the aqueous solution in a container produced by a blow-fill-seal process.   
     
     
         12 . The method according to  claim 1 , further comprising the step of:
 purifying the aqueous solution to remove impurities.   
     
     
         13 . The method according to  claim 1 , wherein:
 the aqueous solution is devoid of viral and microbial impurities.   
     
     
         14 . A method of treating exocrine pancreatic insufficiency, comprising the steps of:
 administering a pharmaceutical preparation comprising an aqueous solution of burlulipase and calcium ions to a patient.   
     
     
         15 . The method according to  claim 14 , further comprising the step of:
 storing the pharmaceutical preparation at room temperature or a temperature greater than room temperature prior to administering the pharmaceutical preparation to the patient.   
     
     
         16 . The method according to  claim 14 , wherein:
 the aqueous solution comprises calcium ions in a concentration of 0.1 to 200 mmol/l.   
     
     
         17 . The method according to  claim 14 , wherein:
 the source of calcium ions is calcium chloride.   
     
     
         18 . The method according to  claim 17 , wherein:
 the aqueous solution comprises calcium chloride in a concentration of 0.1 to 200 mmol/l.   
     
     
         19 . The method according to  claim 17 , wherein:
 the concentration of calcium ions or calcium chloride in the aqueous solution is 0.2 to 100 mmol/l.   
     
     
         20 . A pharmaceutical product comprising an aqueous shelf-stable, pharmaceutical grade solution comprising burlulipase stabilized by solubilized calcium ions, and at least one of 6-deoxy-talane, lipids, and rhamnolipids. 
     
     
         21 . The pharmaceutical product according to  claim 20  for the treatment of exocrine pancreatic insufficiency. 
     
     
         22 . The pharmaceutical product according to  claim 21  for the treatment of pancreatic insufficiency in patients with mucoviscidosis. 
     
     
         23 . The pharmaceutical product according to  claim 22  for use after sequential storage. 
     
     
         24 . The pharmaceutical product according to  claim 20  for use in pediatrics.