Pharmaceutical compositions of tenecteplase

Abstract

Pharmaceutical compositions of tenecteplase that are safe and effective in the treatment of acute ischemic stroke compared with the known compositions are disclosed. The compositions of the invention are invented based on a series of testing trials on the different amounts of the TNK and isolating specific amount that is optimally suitable in terms of desired effects of TNK in the treatment of acute ischemic stroke.

1 . A pharmaceutical composition as an intravenous bolus injection for treatment of acute ischemic stroke in human subjects comprising:
 a. an effective and safe amount of tenecteplase, which is prepared by a perfusion-based continuous fermentation process;   b. a pharmaceutically acceptable inorganic buffer;   c. pharmaceutically acceptable stabilising agents; and   d. optionally, a pharmaceutically acceptable carrier.   
     
     
         2 . A composition of  claim 1  wherein the effective and safe dose of tenecteplase is about 0.10 to 0.24 mg/kg body weight when administered. 
     
     
         3 . A composition of  claim 1  wherein the effective and safe dose of tenecteplase is about 0.20 mg/kg body weight when administered. 
     
     
         4 . A composition of  claim 1  wherein the tenecteplase is prepared in a continuous perfusion fermentation system using Chinese Hamster Ovary cells. 
     
     
         5 . A composition of  claim 1  wherein the buffer used is preferably -phosphoric acid/phosphate buffer. 
     
     
         6 . A composition of  claim 1  wherein the stabilising agent used is preferably L-arginine. 
     
     
         7 . A composition of  claim 1  wherein another stabilising agent used is preferably a polysorbate. 
     
     
         8 . A composition of  claim 1  wherein the components are lyophilised to powder form for reconstitution with water for injection before use. 
     
     
         9 . A composition of  claim 1  wherein the total dose of composition is given as an intravenous bolus in 10 seconds within 6 hours of the onset of the stroke incident. 
     
     
         10 . A pharmaceutical kit comprising:
 (a) a vial contenting lyophilised tenecteplase formulation; and   (b) instructions for using the formulation to treat acute ischemic stroke in human subjects by administering the tenecteplase dose of no more than 0.20 mg/kg body weight given as an intravenous bolus within 10 seconds.   
     
     
         11 . A kit of  claim 10  wherein the amount of tenecteplase is about 2 mg/mL upon reconstitution with water for injection. 
     
     
         12 . A kit of  claim 10  wherein the total dose is given as an intravenous bolus within 6 hours of the onset of the acute ischemic stroke incident. 
     
     
         13 . A kit of  claim 10  wherein the optimum of amount of tenecteplase for bolus dose is about 0.20 mg/kg body weight. 
     
     
         14 . A kit of  claim 10  wherein the total dose is given as a bolus not more than 10 seconds. 
     
     
         15 . (canceled) 
     
     
         16 . A method for treating acute ischemic stroke in a human subject in need thereof, the method comprising administering a pharmaceutical composition as an intravenous bolus injection comprising:
 a. an effective and safe amount of tenecteplase, which is prepared by a perfusion-based continuous fermentation process;   b. a pharmaceutically acceptable inorganic buffer;   c. a pharmaceutically acceptable stabilising agent; and   d. optionally, a pharmaceutically acceptable carrier.