Tranexamic acid oral solution

Abstract

Methods and compositions are provided for treating a patient having a bleeding disorder during or after a dental procedure to reduce bleeding or need for factor replacement therapy. Aqueous pharmaceutical compositions are provided comprising tranexamic acid, sodium carboxymethyl cellulose, Tween® 20, and menthol wherein the composition exhibits good long term stability, little to no discoloration over time, and reduced bitterness compared to a control solution of tranexamic acid and water.

We claim: 
     
         1 . A method for reducing or preventing hemorrhage in a patient's oral cavity during or following a dental procedure, comprising:
 topically administering in the oral cavity to a patient in need of such treatment   a therapeutically effective amount of an aqueous pharmaceutical solution comprising:
 about 3% wt/vol to about 7% wt/vol tranexamic acid; 
 greater than 50 wt % water; 
 wt % to 1 wt % polyoxyethylene sorbitan monolaurate; 
 wt % to 0.5 wt % sodium carboxymethyl cellulose; 
 about 3 wt % to about 6 wt % propylene glycol; 
 about 0.01 wt % to about 0.2 wt % menthol; 
 about 0.02 wt % to about 0.5 wt % of a mixture of propyl paraben and methyl paraben; and a pH 
 adjuster in an amount sufficient to adjust the pH to 4.5 to 6.5; 
   wherein
 (a) the solution does not include carvone or a flavoring agent containing an aldehyde moiety, 
 (b) the solution retains at least about 90% of the tranexamic acid in solution in undegraded form after storage for 6 months at about 25° C. and about 40% relative humidity; and 
 (c) the solution exhibits minimal discoloration as determined by deltaE*<5 after storage for 6 months at about 25° C. and about 40% relative humidity. 
   
     
     
         2 . The method of  claim 1 , wherein the patient has a bleeding disorder, is under fibrinolytic or thrombolytic agent therapy, and/or is on anticoagulant therapy. 
     
     
         3 . The method of  claim 2 , wherein the patient is suffering from a bleeding disorder selected from hemophilia A, hemophilia B, von Willebrand disease or a factor deficiency. 
     
     
         4 . The method of  claim 2 , wherein the patient is taking a fibrinolytic or thrombolytic agent selected from streptokinase, tissue plasminogen activator or urokinase. 
     
     
         5 . The method of  claim 1 , wherein the solution is administered topically as a mouth rinse in a swish and spit format in an amount of 2 mL to 20 mL for about 30 seconds to 4 minutes per administration. 
     
     
         6 . The method of  claim 5 , wherein the solution is administered three to six times per day for a period of one to 10 days. 
     
     
         7 . The method of  claim 6 , wherein tranexamic acid is present in the solution in an amount of 5% wt/vol, and about 10 mL of the composition is administered 4-5 times daily for a period of 7 days. 
     
     
         8 . The method of  claim 1 , wherein the solution is administered during and/or following a dental procedure, such as tooth extraction or scaling. 
     
     
         9 . The method of  claim 1 , wherein the solution exhibits an average palatability score of at least two points higher than a control solution consisting of tranexamic acid and water. 
     
     
         10 . The method of  claim 9 , wherein the solution exhibits an average palatability score of at least three points higher than a control solution consisting of tranexamic acid and water. 
     
     
         11 . The method of  claim 1 , wherein the solution exhibits lower average bitterness than a control solution consisting of tranexamic acid and water and scores at least 1.0 average points higher on a 5 point bitterness scale wherein 1 is most bitter and 5 is least bitter. 
     
     
         12 . The method of  claim 1 , wherein the pH adjuster is phosphoric acid. 
     
     
         13 . The method of  claim 12 , wherein the phosphoric acid is present in an amount to adjust the pH of the solution to about 5.5. 
     
     
         14 . The method of  claim 1 , wherein the pH adjuster is present in an amount to adjust the pH of the solution to about 5.5. 
     
     
         15 . The method of  claim 1 , wherein the solution comprises from about 4% wt/vol to about 6% wt/vol tranexamic acid. 
     
     
         16 . The method of  claim 1 , wherein the solution comprises from about 5% wt/vol tranexamic acid. 
     
     
         17 . The method of  claim 1 , wherein the solution comprises from about 30 mg/ml to about 70 mg/ml tranexamic acid. 
     
     
         18 . The method of  claim 1 , wherein the solution comprises from about 40 mg/ml to about 60 mg/ml tranexamic acid. 
     
     
         19 . The method of  claim 1 , wherein the solution comprises from about 50 mg/ml tranexamic acid.