Antimicrobial locking solutions comprising taurinamide derivatives and biologically acceptable salts and acids, with the addition of small concentrations of heparin

Abstract

The present invention relates to inhibiting or preventing infection and protecting against patency complications after a blood catheter has been inserted in a patient comprising administering to the device a pharmaceutically effective amount of a composition comprising: (A) at least one taurinamide derivative, (B) at least one compound selected from the group consisting of biologically acceptable acids and biologically acceptable salts thereof; and (C) heparin at a low concentration.

1 . A locking solution composition for treating and preventing infection and flow reduction in blood catheters comprising a solution of:
 a. at least one taurinamide derivative;   b. a biologically acceptable acid and a biologically acceptable salt of said acid in a combination that brings the pH of the combination into a range that enhances antimicrobial activity of the taurinamide derivative; and   c. low concentration heparin, wherein the heparin concentration is sufficient to prevent reactions of the taurinamide derivative with stagnant blood but low enough that expulsion and/or spillage of the solution into a patient's bloodstream carries a low risk of patient hemorrhage.   
     
     
         2 . The composition of  claim 1  wherein the biologically acceptable acid is chosen from the group citric acid and lactic acid and the biologically acceptable salt is chosen from the group citrate and lactate. 
     
     
         3 . The composition of  claim 1  wherein the taurinamide derivative is taurolidine, the biologically acceptable acid is citric acid, the biologically acceptable salt is citrate, and the pH range is 5.2 to 6.5. 
     
     
         4 . The composition of  claim 3  wherein low concentration heparin is in the range of 50 to 2500 units per ml. 
     
     
         5 . The composition of  claim 4  wherein low concentration heparin is in the range of 50 to 1750 units per ml. 
     
     
         6 . The composition of  claim 4  wherein low concentration heparin is in the range of 50 to 500 units per ml. 
     
     
         7 . The composition of  claim 4  wherein the low concentration heparin is in the range 50 to 150 units per ml. 
     
     
         8 . A method of enhancing the antimicrobial activity and resistance to flow reduction produced by a catheter locking solution comprising taurolidine in combination with citrate and citric acid by maintaining the pH in the range of 5.2 to 6.5 and of protecting a catheter against taurolidine reaction with blood therein by adding low concentration heparin. 
     
     
         9 . The method of  claim 8  wherein low concentration heparin is in the range of 50 to 2500 units per ml. 
     
     
         10 . The method of  claim 8  in which the low concentration heparin is in the range of 50 units per ml to 1750 units per ml. 
     
     
         11 . The method of  claim 8  in which the low concentration heparin is in the range of 50 units per ml to 500 units per ml. 
     
     
         12 . The method of  claim 8  in which the low concentration heparin is in the range of 50 units per ml to 150 units per ml. 
     
     
         13 . A composition for treating and preventing infection and patency loss in hemodialysis catheters comprising a locking solution comprising:
 a. at least one taurinamide derivative; and   b. low concentration heparin, wherein the heparin concentration is sufficient to prevent reactions of the taurinamide derivative with stagnant blood but low enough that expulsion and/or spillage of the solution into a patient's bloodstream carries a low risk of patient hemorrhage.   
     
     
         14 . The composition of  claim 13  wherein the taurinamide derivative is taurolidine. 
     
     
         15 . The composition of  claim 13  wherein heparin is added in concentration in the range of 50 to 2500 units per ml. 
     
     
         16 . The composition of  claim 13  wherein low concentration heparin is in the range of 50 to 1750 units per ml. 
     
     
         17 . The composition of  claim 13  wherein low concentration heparin is in the range of 50 to 500 units per ml. 
     
     
         18 . The composition of  claim 13  wherein the low concentration heparin is in the range 50 to 150 units per ml. 
     
     
         19 . A locking solution composition for treating and preventing infection and flow reduction in catheters comprising a solution of:
 a. at least one taurinamide derivative;   b. a biologically acceptable acid in sufficient concentration to bring the pH of the composition into a range that enhances antimicrobial activity of the taurinamide derivative; and   c. low concentration heparin, wherein the heparin concentration is sufficient to prevent reactions of the taurinamide derivative but low enough that expulsion and/or spillage of the solution into a patient's bloodstream carries a low risk of patient hemorrhage.   
     
     
         20 . The composition of  claim 19  wherein the taurinamide derivative is taurolidine. 
     
     
         21 . The composition of  claim 19  wherein heparin is added in concentration in the range of 50 to 2500 units per ml. 
     
     
         22 . The composition of  claim 19  wherein low concentration heparin is in the range of 50 to 1750 units per ml. 
     
     
         23 . The composition of  claim 19  wherein the low concentration heparin is in the range 50 to 500 units per ml. 
     
     
         24 . The composition of  claim 19  wherein the low concentration heparin is in the range 50 to 150 units per ml.