Intranasal epinephrine formulations and methods for the treatment of disease

Inventors

Lowenthal, Richard • Maggio, Edward T. • Bell, Robert G. • Shah, Pratik

Assignees

Aegis Therapeutics LLC

Abstract

Drug products adapted for nasal delivery comprising formulations with epinephrine and devices comprising such formulations are provided. Methods of treating anaphylaxis with epinephrine products are also provided.

Core Innovation

The document describes intranasal epinephrine nasal spray drugs and devices for treating a type-1 hypersensitivity reaction in a mammal in need thereof. The treatment uses intranasal administration of between about 25 μL and about 250 μL of a liquid nasal spray pharmaceutical formulation comprising between about 0.1 mg and about 2.4 mg of epinephrine or a salt thereof and an alkylglycoside, optionally including other agents as excipients selected from isotonicity agents, stabilizing agents, antioxidants, preservatives, and pH adjustment agents.

The nasal spray pharmaceutical formulation is a water, water-ethanol, or water-propylene glycol solution, with a pH between about 2.0 and 6.0 and a total volume between about 25 μL and about 250 μL. In particular embodiments, dodecyl maltoside is included, along with benzalkonium chloride and EDTA or disodium salt thereof, and optional agents selected from defined groups for isotonicity, stabilization, antioxidation, preservation, and pH adjustment.

The document emphasizes pharmacokinetic performance relative to an intramuscular injection reference, using intranasal administration volume constraints and pharmacokinetic criteria. It states that intranasal administration of between about 50 μL and about 250 μL provides pharmacokinetic features compared to a 0.5 mg intramuscular injection, including AUC ratios and Cmax and tmax thresholds, and that a single dose of a formulation containing an alkylglycoside achieves an epinephrine Cmax about 2-fold or greater than administering without the alkylglycoside.

Claims Coverage

The consolidated claims include one independent method claim and multiple independent nasal spray formulation claims. Across these claims, the inventive features center on intranasal epinephrine with an alkylglycoside, defined spray volume, epinephrine amount, solution type, pH, total volume, and specific excipient packages including dodecyl maltoside, benzalkonium chloride, and EDTA or disodium EDTA.

Overall, the independent claims cover an intranasal method and multiple nasal spray formulations in which epinephrine is combined with an alkylglycoside, including dodecyl maltoside, with constraints on nasal spray volume, epinephrine amount, solution type, and pH between about 2.0 and 6.0. Several formulation claims further specify benzalkonium chloride and EDTA or disodium EDTA with sodium chloride, and allow optional excipients from defined categories. The independent method claim is tied to intranasal treatment of a type-1 hypersensitivity reaction, and dependent claim text references pharmacokinetic relationships versus an intramuscular injection reference for certain dosing.

Stated Advantages

Documented Applications