Injectable neurosteroid formulations containing nanoparticles

Abstract

The disclosure provides an injectable neurosteroid nanoparticle formulation comprising nanoparticles having a D50 of less than 2000 nm the nanoparticles comprising a neurosteroid of Formula I, where the variables R1-R9 and X are defined herein and at least one surface stabilizer. The surface stabilizer can be a polymeric surface stabilizer such as hydroxyethyl starch, dextran, or povidone. The injectable neurosteroid nanoparticle formulation can be an intravenous formulation. The disclosure also provides a lyophilized powder of the injectable neurosteroid nanoparticle formulation that can be reconstituted in an aqueous solution prior to administration. The disclosure provides injectable neurosteroid nanoparticle formulations and dry powders of such formulations that have been sterilized byebeam irradiation. The disclosure provides a method of treating a patient having a seizure disorder, stroke, or traumatic brain injury, comprising administering an effective amount of the injectableneurosteroid nanoparticle formulation. The disclosure also provides combination methods in which the injectable neurosteroid nanoparticle formulation is a first active agent that is administered in combination with at least one additional active agent.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 62 / 242,601, filed October 16, 2015, which is hereby incorporated by reference in its entirety. Background technique [0003] Pregnane neurosteroids are a class of compounds useful as anesthetics, sedatives, hypnotics, anxiolytics and anticonvulsants. These compounds are characterized by very low water solubility, which limits their formulation options. Injectable formulations of pregnane neurosteroids are particularly desirable because these compounds are used for clinical indications (such as anesthesia) where oral administration is not possible, and especially for the treatment of active seizures. [0004] Status epilepticus (SE) is a severe seizure disorder in which a person with epilepsy experiences seizures lasting more than 5 minutes, or more than 5 minutes in a 5-minute period without recovery between seizures. A seizure. In some cases, c...

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Problems solved by technology

There are currently no approved treatments for pediatric epilepsy in women with PCDH19

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