Organ preservation and/or perfusion solutions that are ph-stabilized and heat sterilized

Abstract

An organ preservation and/or perfusion solution for an isolated tissue or organ is provided. The solution comprises dextran, glucose, calcium ions, a buffer, and water, has a pH of 6.6 to 7.8, and is sterile based on having been subjected to heat sterilization. A method of preparing the solution also is provided. The method comprises combining dextran, glucose, calcium ions, buffer, and water to obtain an initial solution, adjusting the pH of the initial solution to 7.0 to 7.8 if needed, and subjecting the initial solution to heat sterilization, thereby obtaining the organ preservation and/or perfusion solution. A method of preserving and/or perfusing an isolated tissue or organ also is provided. A method for flushing, storage, and/or transportation of an isolated lung after removal from a donor in preparation for eventual transplantation into a recipient also is provided.

1 . A method of preserving and/or perfusing an isolated tissue or organ comprising steps of (1) obtaining a volume of an organ preservation and/or perfusion solution for an isolated tissue or organ from a sterile container in which the solution has been stored; and (2) administering the obtained volume of the solution to the isolated tissue or organ, thereby preserving and/or perfusing the isolated tissue or organ, wherein:
 the solution comprises dextran, glucose, calcium ions, a buffer, and water;   the solution has a pH of 6.6 to 7.8 and is sterile based on having been subjected to heat sterilization;   the dextran is present in the solution at a concentration of 40 to 60 g/L;   the glucose was present in the solution at 0.5 to 5 g/L before the heat sterilization; and   the solution had a pH of 7.0 to 7.8 before the heat sterilization.   
     
     
         2 . The method according to  claim 1 , wherein the obtaining of step (1) comprises inserting sterile tubing into the sterile container and allowing the volume of the solution to flow from the sterile container through the sterile tubing, and the administering of step (2) comprises administering the obtained volume of the solution from the sterile tubing to the isolated tissue or organ. 
     
     
         3 . The method according to  claim 1 , wherein the administering of step (2) is carried out at hypothermia of less than or equal to 25° C. 
     
     
         4 . The method according to  claim 1 , wherein the obtained volume of the solution is not supplemented with additional ingredients during or between steps (1) and (2). 
     
     
         5 . The method according to  claim 1 , wherein the dextran has a weight average molecular weight (Mw) of 20000 to 70000 daltons. 
     
     
         6 . The method according to  claim 5 , wherein the dextran comprises Dextran 40. 
     
     
         7 . The method according to  claim 1 , wherein glucose degradation during heat sterilization was less than 10%. 
     
     
         8 . The method according to  claim 1 , wherein the calcium ions are present in the solution at a concentration of 0.3 to 1.5 mM. 
     
     
         9 . The method according to  claim 1 , wherein the buffer comprises an organic or biological buffer that is present in the solution at a concentration of 1 to 15 mM. 
     
     
         10 . The method according to  claim 9 , wherein the organic or biological buffer comprises tris(hydroxymethyl)aminomethane (TRIS) at a concentration of 1 to 5 mM. 
     
     
         11 . The method according to  claim 1 , wherein the solution further comprises phosphate ions. 
     
     
         12 . The method according to  claim 11 , wherein the phosphate ions are present in the solution at a concentration of 0.2 to 0.8 mM. 
     
     
         13 . A method for flushing, storage, and/or transportation of an isolated lung after removal from a donor in preparation for eventual transplantation into a recipient, the method comprising steps of: (1) flushing the isolated lung of the donor with a flushing volume of an organ preservation and/or perfusion solution for an isolated tissue or organ, and (2) filling a sterile organ storage container at least partially with a filling volume of the solution, and immersing the isolated lung in the filling volume of the solution, wherein:
 the solution comprises dextran, glucose, calcium ions, a buffer, and water;   the solution has a pH of 6.6 to 7.8 and is sterile based on having been subjected to heat sterilization;   the dextran is present in the solution at a concentration of 40 to 60 g/L;   the glucose was present in the solution at 0.5 to 5 g/L before the heat sterilization; and   the solution had a pH of 7.0 to 7.8 before the heat sterilization.   
     
     
         14 . The method according to  claim 13 , wherein the flushing of step (1) is initially carried out at room temperature, then at 2 to 8° C., and the filling of step (2) is carried out at 2 to 8° C. 
     
     
         15 . The method according to  claim 13 , wherein the flushing of step (1) results in an effluent of the isolated lung and is carried out until the effluent is clear. 
     
     
         16 . The method according to  claim 13 , further comprising steps of (3) sealing the sterile organ storage container, with the isolated lung contained therein, with a sterile closure; and then (4) maintaining the sterile organ storage container at 2 to 8° C. for up to 12 hours prior to transplantation of the isolated lung into the recipient, wherein steps (3) and (4) are carried out after steps (1) and (2). 
     
     
         17 . The method according to  claim 13 , wherein the flushing volume of the solution is obtained from one or more sterile containers in which the solution has been stored, and further wherein the flushing volume of the solution is not supplemented with additional ingredients before or during step (1). 
     
     
         18 . The method according to  claim 13 , wherein the filling volume of the solution is obtained from one or more sterile containers in which the solution has been stored, and further wherein the filling volume of the solution is not supplemented with additional ingredients before or during step (2). 
     
     
         19 . The method according to  claim 13 , wherein the dextran has a weight average molecular weight (Mw) of 20000 to 70000 daltons. 
     
     
         20 . The method according to  claim 13 , wherein the buffer comprises an organic or biological buffer that is present in the solution at a concentration of 1 to 15 mM.