Intranasal epinephrine formulations and methods for the treatment of disease
Inventors
Lowenthal, Richard • Maggio, Edward T. • Bell, Robert G. • Shah, Pratik
Assignees
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Publication Number
US-11744895-B2
Publication Date
2023-09-05
Expiration Date
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 invention provides intranasal epinephrine pharmaceutical formulations for treating type-1 hypersensitivity reactions in a human by intranasal administration of a single administered dose. The formulation comprises between about 0.1 mg and about 2.4 mg of epinephrine, or a salt thereof, and epinephrine is the only pharmaceutically active ingredient in the pharmaceutical formulation. The intranasal single dose provides plasma epinephrine concentrations efficacious for eliminating one, more than one, or all of the symptoms of the type-1 hypersensitivity reaction or preventing further progression of the symptoms.
The invention relates to intranasal absorption enhancer excipients for aqueous intranasal epinephrine formulations, with emphasis on alkylsaccharides including alkylglycosides such as dodecyl maltoside, tetradecyl maltoside, and sucrose dodecanoate. The document describes transmucosal absorption enhancement mechanisms and notes GRAS status for the excipients. The partial content links formulation and excipient choices to plasma pharmacokinetic matching with intramuscular epinephrine, including matching plasma concentrations such as Cmax, Tmax, and AUC.
The disclosure also describes intranasal epinephrine drug products as pharmaceutical formulations and nasal spray delivery devices configured for intranasal administration. The formulation and delivery are designed to achieve an injection-like pharmacokinetic profile while mitigating dose-related cardiovascular risks described in the disclosure. The document also describes formulation stabilization and pH adjustment targets for the aqueous intranasal epinephrine formulations, including use of chealating and stabilizing agents such as EDTA, or disodium EDTA.
Claims Coverage
The independent claims cover intranasal treatment methods for type-1 hypersensitivity reactions and related conditions. Across the independent claims, the shared coverage is intranasal, single-dose administration of epinephrine, or a salt thereof, as the only pharmaceutically active ingredient, with a dose between about 0.1 mg and about 2.4 mg and efficacy defined by plasma epinephrine concentrations that eliminate symptoms or prevent further progression.
Intranasal single-dose epinephrine formulation for type-1 hypersensitivity treatment
Intranasal administration of a pharmaceutical formulation comprising between about 0.1 mg and about 2.4 mg of epinephrine, or a salt thereof, in a single administered dose, with epinephrine as the only pharmaceutically active ingredient, wherein intranasal administration provides plasma epinephrine concentrations efficacious for elimination or prevention of further progression of symptoms of a type-1 hypersensitivity reaction.
Intranasal single-dose epinephrine formulation for allergic asthma, allergic conjunctivitis, allergic rhinitis, anaphylaxis, angioedema, urticaria, or eosinophilia
Intranasal administration of a pharmaceutical formulation comprising between about 0.1 mg and about 2.4 mg of epinephrine, or a salt thereof, in a single administered dose, with epinephrine as the only pharmaceutically active ingredient, wherein intranasal administration provides plasma epinephrine concentrations efficacious for elimination or prevention of further progression of symptoms of allergic asthma, allergic conjunctivitis, allergic rhinitis, anaphylaxis, angioedema, urticaria, or eosinophilia.
Intranasal single-dose epinephrine formulation for anaphylaxis or acute asthmatic attacks
Intranasal administration of a pharmaceutical formulation to a human with anaphylaxis or acute asthmatic attacks, comprising between about 0.1 mg and about 2.4 mg of epinephrine, or a salt thereof, in a single administered dose, with epinephrine as the only pharmaceutically active ingredient, wherein intranasal administration provides plasma epinephrine concentrations efficacious for elimination or prevention of further progression of symptoms.
Intranasal single-dose epinephrine formulation for idiopathic anaphylaxis or exercise-induced anaphylaxis
Intranasal administration of a pharmaceutical formulation to a human with idiopathic anaphylaxis or exercise-induced anaphylaxis, comprising between about 0.1 mg and about 2.4 mg of epinephrine, or a salt thereof, in a single administered dose, with epinephrine as the only pharmaceutically active ingredient, wherein intranasal administration provides plasma epinephrine concentrations efficacious for elimination or prevention of further progression of symptoms.
Across the independent claims, the core claim structure is consistent: intranasal administration of a single administered dose pharmaceutical formulation containing epinephrine or a salt thereof as the only pharmaceutically active ingredient, with the dose between about 0.1 mg and about 2.4 mg, and efficacy characterized by plasma epinephrine concentrations efficacious to eliminate symptoms or prevent further progression of symptoms for the specified type-1 hypersensitivity reaction categories.
Stated Advantages
Achieves plasma epinephrine concentrations that are efficacious for elimination of one, more than one, or all of the symptoms of the type-1 hypersensitivity reaction.
Achieves plasma epinephrine concentrations that are efficacious for prevention of the further progression of one, more than one, or all of the symptoms of the type-1 hypersensitivity reaction.
Plasma epinephrine concentrations are matched with intramuscular epinephrine, including Cmax, Tmax, and AUC.
The excipients are described as GRAS.
The formulation uses absorption enhancer excipients intended to support intranasal delivery.
Documented Applications
Treatment of a type-1 hypersensitivity reaction in a human by intranasal administration of an epinephrine formulation.
Treatment of allergic asthma, allergic conjunctivitis, allergic rhinitis, anaphylaxis, angioedema, urticaria, or eosinophilia by intranasal administration of an epinephrine formulation.
Treatment of anaphylaxis or acute asthmatic attacks by intranasal administration of an epinephrine formulation.
Treatment of idiopathic anaphylaxis or exercise-induced anaphylaxis by intranasal administration of an epinephrine formulation.
Treatment of type-1 hypersensitivity reactions, including allergic asthma, urticaria, anaphylaxis, acute asthmatic attacks, idiopathic anaphylaxis, and exercise-induced anaphylaxis.
Intranasal delivery of epinephrine formulations.
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