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-11918655-B2
Publication Date
2024-03-05
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 treatment of a type-1 hypersensitivity reaction in a human by administering a nasal spray pharmaceutical formulation comprising epinephrine, or a salt thereof, as the only pharmaceutically active ingredient. The formulation is administered in a defined intranasal dose volume and epinephrine concentration range, and the administration provides plasma epinephrine concentrations efficacious for elimination of one, more than one, or all of the symptoms, or efficacious for prevention of the further progression of one, more than one, or all of the symptoms.
For anaphylaxis, the formulation is administered as a single dose of an aqueous pharmaceutical formulation with one actuation of a single-dose nasal spray device into one nostril. The treatment is defined by epinephrine-only activity, defined dose amount and intranasal volume, and plasma epinephrine concentrations efficacious for elimination of anaphylaxis symptoms with a time to maximum epinephrine plasma concentrations (Tmax) of less than 45 minutes.
The formulation further includes an absorption enhancement agent and additional excipients such as isotonicity agents, stabilizing agents, antioxidants, preservatives, and pH adjustment agents to adjust the pH to a final pH between about 3.0 and about 5.0. In some embodiments, dodecyl maltoside, sodium chloride, EDTA or disodium salt thereof, benzalkonium chloride, sodium metabisulfite, hydrochloric acid, sodium hydroxide, or both are specified.
Claims Coverage
The independent claims cover intranasal epinephrine-only formulations for type-1 hypersensitivity reactions and anaphylaxis, with defined concentration and dose-volume ranges, excipient and pH systems, and a Tmax requirement for anaphylaxis embodiments.
Epinephrine-only intranasal treatment for type-1 hypersensitivity
Intranasally administering a nasal spray pharmaceutical formulation to a human with a type-1 hypersensitivity reaction, where epinephrine, or a salt thereof, is the only pharmaceutically active ingredient, with defined concentration and dose-volume ranges, providing plasma epinephrine concentrations efficacious for elimination of symptoms and/or prevention of further progression of symptoms.
Epinephrine-only intranasal formulation with dodecyl maltoside, sodium chloride, EDTA, benzalkonium chloride, and pH 3.0 to 5.0
Intranasally administering a nasal spray pharmaceutical formulation including dodecyl maltoside as an absorption enhancement agent, sodium chloride as an isotonicity agent, EDTA or disodium salt thereof as a stabilizing agent, benzalkonium chloride as a preservative, optional sodium metabisulfite as an antioxidant, and hydrochloric acid, sodium hydroxide, or both to adjust pH to a final pH between about 3.0 and about 5.0.
Single-dose epinephrine-only intranasal anaphylaxis treatment with Tmax less than 45 minutes
Intranasally administering to a human with anaphylaxis a single dose of an aqueous pharmaceutical formulation comprising about 1.0 mg to about 2.0 mg of epinephrine as the only pharmaceutically active ingredient, with one actuation of a single-dose nasal spray device into one nostril, providing plasma epinephrine concentrations efficacious for elimination of anaphylaxis symptoms with a time to maximum epinephrine plasma concentrations (Tmax) of less than 45 minutes.
The independent claims center on intranasal delivery of epinephrine-only formulations for type-1 hypersensitivity reactions and anaphylaxis, with constrained concentration and dose-volume ranges and plasma epinephrine efficacy for symptom elimination and/or prevention of further progression. Additional claim coverage includes specific excipient systems, a final pH between about 3.0 and about 5.0, and for anaphylaxis embodiments a Tmax limit of less than 45 minutes.
Stated Advantages
Provides plasma epinephrine concentrations efficacious for elimination of one or more symptoms of the type-1 hypersensitivity reaction, including anaphylaxis.
Provides plasma epinephrine concentrations efficacious for prevention of further progression of one or more symptoms of the type-1 hypersensitivity reaction, including anaphylaxis.
In anaphylaxis embodiments, achieves efficacious plasma epinephrine concentrations with a time to maximum epinephrine plasma concentrations (Tmax) of less than 45 minutes.
Documented Applications
Treating type-1 hypersensitivity reactions in a human, including allergic asthma, allergic conjunctivitis, allergic rhinitis, anaphylaxis, angioedema, urticaria, eosinophilia, or combinations thereof.
Emergency treatment of anaphylaxis in a human using a single intranasal actuation into one nostril and achieving efficacious plasma epinephrine with Tmax less than 45 minutes.
Treating anaphylaxis in a human with a single dose aqueous epinephrine-only intranasal formulation delivered with one actuation into one nostril.
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