Claims for Patent: 11,744,895

Summary for Patent: 11,744,895

Title:	Intranasal epinephrine formulations and methods for the treatment of disease
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.
Inventor(s):	Richard Lowenthal, Edward T. Maggio, Robert G. Bell, Pratik Shah
Assignee:	Aegis Therapeutics LLC
Application Number:	US17/396,044
Patent Claims:	1. A method of treatment of a type-1 hypersensitivity reaction in a human comprising an 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 to the human with the type-1 hypersensitivity reaction; wherein epinephrine, or a salt thereof, is the only pharmaceutically active ingredient in the pharmaceutical formulation; and wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the elimination of one, more than one, or all of the symptoms of the type-1 hypersensitivity reaction; or wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the prevention of the further progression of one, more than one, or all of the symptoms of the type-1 hypersensitivity reaction. 2. A method of treatment of a type-1 hypersensitivity reaction in a human, comprising an 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, to the human in need thereof; wherein epinephrine, or a salt thereof, is the only pharmaceutically active ingredient in the pharmaceutical formulation; and wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the elimination of one, more than one, or all of the symptoms of allergic asthma, allergic conjunctivitis, allergic rhinitis, anaphylaxis, angioedema, urticaria, or eosinophilia; or wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the prevention of the further progression of one, more than one, or all of the symptoms of allergic asthma, allergic conjunctivitis, allergic rhinitis, anaphylaxis, angioedema, urticaria, or eosinophilia; and wherein the type-1 hypersensitivity reaction is caused by stinging insects, biting insects, allergen immunotherapy, foods, drugs, diagnostic testing substances or other allergens. 3. A method of treatment of allergic asthma in a human, comprising an 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, to the human in need thereof; wherein epinephrine, or a salt thereof, is the only pharmaceutically active ingredient in the pharmaceutical formulation; and wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the elimination of one, more than one, or all of the symptoms of allergic asthma; or wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the prevention of the further progression of one, more than one, or all of the symptoms of allergic asthma. 4. A method of treatment of urticaria in a human, comprising an 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 to the human in need thereof; wherein epinephrine, or a salt thereof, is the only pharmaceutically active ingredient in the pharmaceutical formulation; and wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the elimination of one, more than one, or all of the symptoms of urticaria; or wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the prevention of the further progression of one, more than one, or all of the symptoms of urticaria. 5. The method of claim 4, wherein the pharmaceutical formulation comprises about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1.0 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2.0 mg, about 2.1 mg, about 2.2 mg, about 2.3 mg, or about 2.4 mg of epinephrine, or a salt thereof, in a single administered dose. 6. The method of claim 4, wherein the pharmaceutical formulation comprises about 0.3 mg, about 0.5 mg, about 1.0 mg, or about 2.0 mg of epinephrine, or a salt thereof, in a single administered dose. 7. The method of claim 4, wherein the pharmaceutical formulation comprises about 1.0 mg or about 2.0 mg of epinephrine, or a salt thereof, in a single administered dose. 8. The method of claim 4, wherein the pharmaceutical formulation further comprises one or more of other agents as excipients selected from the group consisting of absorption enhancement agents, isotonicity agents, stabilizing agents, antioxidants, preservatives, and pH adjustment agents. 9. The method of claim 8, wherein the absorption enhancement agents are selected from the group consisting of surfactants, fatty acids, bile salts, cyclodextrins, phospholipids, and alcohols. 10. The method of claim 8, wherein the absorption enhancement agents are selected from the group consisting of alkylglycosides, polysorbate 20, polysorbate 80, oleic acid, salt of oleic acid, sodium lauryl sulfate, sodium glycocholate, sodium taurocholate, and sodium taurodihydrofusidate. 11. The method of claim 8, wherein the absorption enhancement agents are selected from the group consisting of undecyl maltoside, dodecyl maltoside, tridecyl maltoside, tetradecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate, and sucrose mono-tetradecanoate. 12. The method of claim 8, wherein the absorption enhancement agent is an alkylglycoside. 13. The method of claim 8, wherein the absorption enhancement agent is dodecyl maltoside. 14. The method of claim 8, wherein the isotonicity agents are selected from the group consisting of dextrose, glycerin, mannitol, potassium chloride, and sodium chloride. 15. The method of claim 8, wherein the antioxidants are selected from the group consisting of alpha tocopherol, D-a-tocopherol polyethylene glycol 1000 succinate, ascorbic acid, isoascorbic acid, butylated hydroxyanisole (BHA), citric acid monohydrate, potassium metabisulfite, sodium bisulfite, sodium metabisulfite, and sodium sulfite. 16. The method of claim 8, wherein the pharmaceutical formulation is a water, water-ethanol, or water-propylene glycol solution; and wherein the total volume of the single administered dose of the pharmaceutical formulation is about 25 μL, about 50 μL, about 75 μL, about 100 μL, about 125 μL, about 150 μL, about 175 UL, about 200 μL, or about 250 μL. 17. The method of claim 8, wherein the pharmaceutical formulation is a water solution; and wherein the total volume of the single administered dose of the pharmaceutical formulation is about 25 μL, about 50 μL, about 75 μL, about 100 μL, about 125 μL, about 150 μL, about 175 μL, about 200 μL, or about 250 μL. 18. A method of treatment of anaphylaxis or acute asthmatic attacks in a human, comprising an intranasal administration of a pharmaceutical formulation to the human with anaphylaxis or acute asthmatic attacks; wherein the pharmaceutical formulation comprises between about 0.1 mg and about 2.4 mg of epinephrine, or a salt thereof, in a single administered dose; wherein epinephrine, or a salt thereof, is the only pharmaceutically active ingredient in the pharmaceutical formulation; and wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the elimination of one, more than one, or all of the symptoms of anaphylaxis or acute asthmatic attacks; or wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the prevention of the further progression of one, more than one, or all of the symptoms of anaphylaxis or acute asthmatic attacks. 19. The method of claim 18, wherein the pharmaceutical formulation comprises about 0.3 mg, about 0.5 mg, about 1.0 mg, or about 2.0 mg of epinephrine, or a salt thereof, in a single administered dose. 20. The method of claim 18, wherein the pharmaceutical formulation comprises about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1.0 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2.0 mg, about 2.1 mg, about 2.2 mg, about 2.3 mg, or about 2.4 mg of epinephrine, or a salt thereof, in a single administered dose. 21. The method of claim 18, wherein the symptoms are selected from the group consisting of hives, generalized itching, nasal congestion, wheezing, difficulty breathing, cough, cyanosis, lightheadedness, dizziness, confusion, slurred speech, rapid pulse, palpitations, nausea or vomiting, abdominal pain or cramping, skin redness or inflammation, nasal flaring, and intercostal retractions. 22. The method of claim 18, wherein the pharmaceutical formulation further comprises one or more of other agents as excipients selected from the group consisting of absorption enhancement agents, isotonicity agents, stabilizing agents, antioxidants, preservatives, and pH adjustment agents. 23. The method of claim 22, wherein: the absorption enhancement agents are selected from the group consisting of alkylglycosides, polysorbate 20, polysorbate 80, oleic acid, salt of oleic acid, sodium lauryl sulfate, sodium glycocholate, sodium taurocholate, and sodium taurodihydrofusidate; the isotonicity agents are selected from the group consisting of dextrose, glycerin, mannitol, potassium chloride, and sodium chloride; and the antioxidants are selected from the group consisting of alpha tocopherol, D-a-tocopherol polyethylene glycol 1000 succinate, ascorbic acid, isoascorbic acid, butylated hydroxyanisole (BHA), citric acid monohydrate, potassium metabisulfite, sodium bisulfite, sodium metabisulfite, and sodium sulfite. 24. The method of claim 22, wherein the pharmaceutical formulation is a water, water-ethanol, or water-propylene glycol solution; and wherein the total volume of the single administered dose of the pharmaceutical formulation is about 25 μL, about 50 μL, about 75 μL, about 100 μL, about 125 μL, about 150 μL, about 175 μL, about 200 μL, or about 250 μL. 25. A method of treatment of a type-1 hypersensitivity reaction in a human, comprising an 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, to the human in need thereof; wherein epinephrine, or a salt thereof, is the only pharmaceutically active ingredient in the pharmaceutical formulation; and wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the elimination of one, more than one, or all of the symptoms selected from the group consisting of generalized hives, itching, flushing, angioedema, a burning sensation of the skin, swelling of the tongue or throat, shortness of breath, wheezes, coronary artery spasm, myocardial infarction, dysrhythmia, cardiac arrest, tachycardia, and bradycardia; or wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the prevention of the further progression of one, more than one, or all of the symptoms selected from the group consisting of generalized hives, itching, flushing, angioedema, a burning sensation of the skin, swelling of the tongue or throat, shortness of breath, wheezes, coronary artery spasm, myocardial infarction, dysrhythmia, cardiac arrest, tachycardia, and bradycardia. 26. A method of treatment of idiopathic anaphylaxis or exercise-induced anaphylaxis in a human comprising an intranasal administration of a pharmaceutical formulation to the human with idiopathic anaphylaxis or exercise-induced anaphylaxis; wherein the pharmaceutical formulation comprises between about 0.1 mg and about 2.4 mg of epinephrine, or a salt thereof, in a single administered dose; wherein epinephrine, or a salt thereof, is the only pharmaceutically active ingredient in the pharmaceutical formulation; wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the elimination of one, more than one, or all of the symptoms of the idiopathic anaphylaxis or exercise-induced anaphylaxis; or wherein the intranasal administration of the single administered dose of the pharmaceutical formulation to the human provides plasma epinephrine concentrations in the human that are efficacious for the prevention of the further progression of one, more than one, or all of the symptoms of the idiopathic anaphylaxis or exercise-induced anaphylaxis.