Liquid formulations of compounds active at sulfonylurea receptors

Abstract

The invention provides liquid formulations of compounds that act at sulfonylurea receptors that are suitable for intra-venous and intra-arterial infusion. Compounds active at a sulfonylurea receptor include glibenclamide, tolbutamide, repaglinide, nateglinide, meglitinide, midaglizole, LY397364, LY389382, glyclazide, and glimepiride. Liquid formulations may be concentrated solutions suitable for storage; may be diluted (e.g., dilution of 1:1 or 1:1.2) suitable for bolus injections, and may be further diluted (e.g., dilution of 1:10 or 1:20 or more) for intravenous and intra-arterial infusion over an extended period of time. For example, a liquid formulation may include at least about 0.05 mg/ml glibenclamide in a water-based solution including 40% polyethylene glycol 300, 10% Ethanol, 50% water, at about pH 9. The solution may include a buffer, and is suitable for storage in refrigerator or at room temperature. This solution may be diluted 1:1, or more (e.g., 1:20) without precipitation of the glibenclamide.

1 . A liquid formulation suitable for administration to a patient, comprising:
 glibenclamide at a concentration of at least about 0.04 mg/ml, and a pharmaceutically acceptable infusion solution.   
     
     
         2 . The liquid formulation of  claim 1 , wherein said pharmaceutically acceptable infusion solution comprises water and a pharmaceutically acceptable salt or sugar. 
     
     
         3 . The liquid formulation of  claim 2 , wherein said pharmaceutically acceptable infusion solution comprises water and a pharmaceutically acceptable salt. 
     
     
         4 . The liquid formulation of  claim 1  which has a pH greater than about pH 7.4. 
     
     
         5 . The liquid formulation of  claim 1 , further comprising a buffer, wherein said liquid formulation has a pH of at least about pH 7.4. 
     
     
         6 . The liquid formulation of  claim 1 , further comprising an alcohol. 
     
     
         7 . The liquid formulation of  claim 6 , wherein said alcohol is ethyl alcohol. 
     
     
         8 . The liquid formulation of  claim 1 , further comprising a co-solvent. 
     
     
         9 . The liquid formulation of  claim 1 , further comprising a surfactant. 
     
     
         10 . The liquid formulation of  claim 1 , further comprising an alcohol and a co-solvent. 
     
     
         11 . The liquid formulation of  claim 10 , further comprising a surfactant. 
     
     
         12 . The liquid formulation of  claim 1 , further comprising an alcohol and a co-solvent, wherein said liquid formulation has a pH of at least about pH 7.4 
     
     
         13 . The liquid formulation of  claim 12 , further comprising a surfactant. 
     
     
         14 . (canceled) 
     
     
         15 . The liquid formulation of  claim 10 , wherein said alcohol comprises ethyl alcohol. 
     
     
         16 . The liquid formulation of  claim 10 , wherein said co-solvent comprises a co-solvent selected from propylene glycol and a polyalkylene glycol. 
     
     
         17 . The liquid formulation of  claim 16 , wherein said co-solvent is selected from propylene glycol (PG), polyethylene glycol (PEG), polybutylene glycol and polypropylene glycol. 
     
     
         18 . The liquid formulation of  claim 16 , wherein said polyalkylene glycol comprises PEG 300. 
     
     
         19 . The liquid formulation of  claim 16 , wherein said polyalkylene glycol comprises PEG 400. 
     
     
         20 . The liquid formulation of  claim 16 , wherein said co-solvent comprises propylene glycol (PG). 
     
     
         21 . A liquid formulation suitable for intravenous or intra-arterial administration, comprising:
 a compound which is pharmaceutically active at a sulfonylurea receptor, said compound at a concentration of at least about 0.04 mg/ml, ethanol, water, and a co-solvent.   
     
     
         22 - 89 . (canceled)