LIQUID FORMULATIONS OF COMPOUNDS ACTIVE AT SULFONYLUREA RECEPTORS
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)