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.

Description

FIELD OF THE INVENTION[0001]The present invention provides liquid formulations of compounds active at sulfonylurea receptors and suitable for administration to a patient in need of treatment with such compounds, methods for using the novel formulations, and kits providing the formulations for clinical use.BACKGROUND OF THE INVENTION[0002]Macromolecules termed “sulfonylurea receptors” (SUR) are found in many body tissues and are important in many physiological activities. Among many important functions, SUR are involved in insulin release from pancreatic beta cells, and may affect blood pressure by affecting vascular smooth muscle. There are multiple SUR, including a type 1 sulfonylurea receptor (SUR1), a type 2 sulfonylurea receptor (SUR2) and subtypes of these receptors. Molecularly distinct SURs are coupled to distinct ion channel moieties in various tissues to form, for example, different KATP channels with distinguishable physiological and pharmacological characteristics. KATP c...

AI Technical Summary

Benefits of technology

[0015]Accordingly, it will be understood that disclosed herein are also methods for administering a SUR-active compound to a patient in need of treatment with a SUR-active compound. For example, provided herein are methods of treating a patient suffering from stroke, head trauma, spinal cord injury, cardiac arrest leading to an interruption of blood flow to the brain, or other condition in which the sufferer is at risk of brain swelling or neural cell swelling comprising administration of an effective dose of a SUR-active compound provided via a liquid formulation of a SUR-active compound having features of the invention. Methods of treating a patient in need of administration of a SUR-active compound include intravenous, intra-arterial, intrathecal, parenteral, intraperitoneal, intracerebroventricular, subcutaneous, oral, buccal, sublingual, intracavernous

Problems solved by technology

Such drugs are typically poorly water soluble, and are commonly given as pills or in other solid form.

However, some patients are not able to swallow pills, or otherwise would be better served if these drugs were readily available for delivery in another form besides solid pills or powders.

Oral administration of solid d

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