Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12133915-B2
Publication Date
2024-11-05
Expiration Date
Abstract
Alprazolam formulated as an inhaled condensation aerosol and method for treating epilepsy and/or seizures.
Core Innovation
The invention provides a method for stopping an ongoing seizure in a subject in need thereof by administering alprazolam via a breath-activated inhalation device during the ongoing seizure, wherein the ongoing seizure has not progressed to status epilepticus. The method administers alprazolam in a dose of about 1 mg to about 2 mg and is characterized by stopping the ongoing seizure within 2 minutes of inhalation of alprazolam.
The breath-activated inhalation device includes a first element for rapidly heating a heat-conductive, impermeable substrate coated with an alprazolam composition to form a vapor. The device further includes a second element allowing the vapor to cool, thereby providing a condensation aerosol comprising alprazolam particles, and a third element permitting inhalation of the condensation aerosol.
The documented therapeutic rationale and clinical context described include acute seizure treatment aimed at stopping seizures during early phases, including prodrome and aura, before progression toward status epilepticus. Pharmacokinetic and aerosol performance attributes are described, including rapid onset with maximal effect within minutes and bioavailability relative to intravenous administration, and a photosensitive epilepsy proof-of-concept study is described using intermittent photic stimulation, with inhaled alprazolam reducing Standard Photosensitivity Range (SPR) and showing time-correlated EEG and sedation effects with tolerable safety signals.
Claims Coverage
The claim coverage centers on one independent claim that stops an ongoing seizure, not progressed to status epilepticus, by inhaled alprazolam delivered using a breath-activated condensation-aerosol device. Dependent claims refine patient and seizure context and constrain dosing, stopping time, bioavailability, particle size, condensation-aerosol formation, and plasma Tmax.
Inhaled alprazolam via a breath-activated condensation aerosol device to stop an ongoing seizure
A method for stopping an ongoing seizure in a subject in need thereof by administering alprazolam via a breath-activated inhalation device during the ongoing seizure that has not progressed to status epilepticus, administering alprazolam in a dose of about 1 mg to about 2 mg, wherein the device rapidly heats a heat-conductive, impermeable substrate coated with an alprazolam composition to form a vapor, cools the vapor to provide a condensation aerosol comprising alprazolam particles, and permits inhalation, whereby the ongoing seizure is stopped within 2 minutes of inhalation of alprazolam.
Bioavailability relative to intravenous administration
The method further characterizes alprazolam such that bioavailability is about 80% to about 125% of the bioavailability achieved with alprazolam administered intravenously.
Particle size threshold for alprazolam in the condensation aerosol
The method further characterizes alprazolam particles such that at least 80% by weight have a size less than 5 microns.
Condensation-aerosol formation using an alprazolam film and vaporization by heating
The method further specifies providing a condensation aerosol by preparing an alprazolam film of a thickness between 0.05 and 20 microns on a heat-conductive and impermeable substrate and heating the substrate to at least 300°C to vaporize the alprazolam.
Rapid pharmacokinetic onset with plasma Tmax
The method further characterizes alprazolam such that alprazolam shows a plasma Tmax of less than 2 minutes after administration.
The claim set centers on stopping an ongoing seizure before status epilepticus by breath-activated inhalation of alprazolam formulated and delivered as a condensation aerosol. Dependent claims further limit relative bioavailability to intravenous dosing, alprazolam particle size, condensation-aerosol formation via an alprazolam film on a heat-conductive impermeable substrate with vaporization by heating, and rapid plasma Tmax.
Stated Advantages
The ongoing seizure is stopped within 2 minutes of inhalation of alprazolam.
Bioavailability is about 80% to about 125% of that achieved with alprazolam administered intravenously.
Alprazolam plasma Tmax is less than 2 minutes after administration.
In a photosensitive epilepsy proof-of-concept study, inhaled alprazolam rapidly reduces Standard Photosensitivity Range (SPR) with time-correlated EEG and sedation effects and tolerable safety signals.
Documented Applications
Treatment of epilepsy and seizures by stopping an ongoing seizure in a subject, including use in photosensitive epilepsy with intermittent photic stimulation and measurement of Standard Photosensitivity Range (SPR).
Acute seizure treatment during prodrome and aura phases prior to progression toward status epilepticus, supported by documented photosensitive epilepsy proof-of-concept results.
Interested in licensing this patent?