Claims for Patent: 12,324,838

Summary for Patent: 12,324,838

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:	US18/327,621
Patent Claims:	1. A single-use, pre-primed nasal spray device comprising a single reservoir containing a nasal spray pharmaceutical formulation, wherein, the nasal spray pharmaceutical formulation has a volume between about 100 μL and about 140 μL and consists of: between about 1 mg/mL and about 40 mg/mL of epinephrine, or a salt thereof; water; an alkyl glycoside; one or more isotonicity agents selected from the group consisting of dextrose, glycerin, mannitol, potassium chloride, and sodium chloride; optionally ethylenediaminetetraacetic acid (EDTA) or disodium salt thereof, as a stabilizing agent; optionally benzalkonium chloride as a preservative; optionally one or more antioxidants selected from the group consisting of alpha tocopherol, D-α-tocopherol polyethylene glycol 1000 succinate, ascorbic acid, isoascorbic acid, butylated hydroxyanisole, citric acid monohydrate, potassium metabisulfite, sodium bisulfite, sodium metabisulfite, and sodium sulfite; and optionally one or more pH adjustment agents selected from the group consisting of adipic acid, ammonium chloride, citric acid, acetic acid, hydrochloric acid, lactic acid, phosphoric acid, propionic acid, sulfuric acid, tartaric acid, sodium hydroxide, sodium citrate, sodium bicarbonate, sodium carbonate, and combinations thereof, to adjust the pH to a final pH between about 2.0 and about 6.0; wherein one actuation of the nasal spray device delivers about 100 μL of the nasal spray pharmaceutical formulation into one nostril of a human. 2. The nasal spray device of claim 1, wherein: the nasal spray pharmaceutical formulation consists of between about 5 mg/mL and about 40 mg/ml of epinephrine; water; an alkyl glycoside that is dodecyl maltoside; sodium chloride; ethylenediaminetetraacetic acid (EDTA) or disodium salt thereof; benzalkonium chloride; sodium metabisulfite; and hydrochloric acid, sodium hydroxide, or both hydrochloric acid and sodium hydroxide as pH adjustment agents to adjust the pH to a final pH between about 3.0 and about 5.0. 3. The nasal spray device of claim 1, wherein: the nasal spray pharmaceutical formulation consists of about 3 mg/mL, about 4 mg/mL, about 5 mg/mL, about 6 mg/mL, about 7 mg/mL, about 8 mg/mL, about 9 mg/mL, about 10 mg/mL, about 11 mg/mL, about 12 mg/mL, about 13 mg/mL, about 14 mg/mL, about 15 mg/mL, about 16 mg/mL, about 17 mg/mL, about 18 mg/mL, about 19 mg/mL, or about 20 mg/ml of epinephrine; water; an alkyl glycoside that is dodecyl maltoside; sodium chloride; ethylenediaminetetraacetic acid (EDTA) or disodium salt thereof; benzalkonium chloride; optionally sodium metabisulfite; and hydrochloric acid, sodium hydroxide, or both hydrochloric acid and sodium hydroxide as pH adjustment agents to adjust the pH to a final pH between about 3.0 and about 5.0. 4. The nasal spray device of claim 1, wherein: the nasal spray pharmaceutical formulation consists of about 10 mg/mL, about 11 mg/mL, about 12mg/mL, about 13 mg/mL, about 14 mg/mL, about 15 mg/mL, about 16 mg/mL, about 17mg/mL, about 18 mg/mL, about 19 mg/mL, or about 20 mg/mL of epinephrine; water; an alkyl glycoside that is dodecyl maltoside; sodium chloride; ethylenediaminetetraacetic acid (EDTA) or disodium salt thereof; benzalkonium chloride; optionally sodium metabisulfite; and hydrochloric acid, sodium hydroxide, or both hydrochloric acid and sodium hydroxide as pH adjustment agents to adjust the pH to a final pH between about 3.0 and about 5.0. 5. A single-use, pre-primed nasal spray device comprising a single reservoir containing a nasal spray pharmaceutical formulation, wherein the nasal spray device is a single-dose nasal spray device and one actuation of the single-dose nasal spray device emits about 100 μL of a nasal spray pharmaceutical formulation, wherein the emitted nasal spray pharmaceutical formulation consists of 1 mg of epinephrine, water, dodecyl maltoside, sodium chloride, benzalkonium chloride, disodium salt of ethylenediaminetetraacetic acid (EDTA), sodium metabisulfite, and hydrochloric acid, sodium hydroxide, or both hydrochloric acid and sodium hydroxide as pH adjustment agents to adjust the pH to a final pH between about 3.0 and about 5.0. 6. A single-use, pre-primed nasal spray device comprising a single reservoir containing a nasal spray pharmaceutical formulation, wherein the nasal spray device is a single-dose nasal spray device and one actuation of the single-dose nasal spray device emits about 100 μL of a nasal spray pharmaceutical formulation, wherein the emitted nasal spray pharmaceutical formulation consists of 2 mg of epinephrine water, dodecyl maltoside, sodium chloride, benzalkonium chloride, disodium salt of ethylenediaminetetraacetic acid (EDTA), sodium metabisulfite, and hydrochloric acid, sodium hydroxide, or both hydrochloric acid and sodium hydroxide as pH adjustment agents to adjust the pH to a final pH between about 3.0 and about 5.0. 7. A single-use, pre-primed nasal spray device comprising a single reservoir containing a nasal spray pharmaceutical formulation, wherein the nasal spray pharmaceutical formulation has a volume between about 100 μL and about 140 μL and consists of about 10 mg/mL or 20 mg/mL of epinephrine; water; dodecyl maltoside; sodium chloride; ethylenediaminetetraacetic acid (EDTA) or disodium salt thereof; benzalkonium chloride; sodium metabisulfite; and hydrochloric acid, sodium hydroxide, or both hydrochloric acid and sodium hydroxide, to adjust the pH to a final pH between about 3.0 and about 5.0; and wherein one actuation of the nasal spray device delivers about 100 μL of the nasal spray pharmaceutical formulation into one nostril of a human. 8. A single-use, pre-primed nasal spray device comprising a single reservoir containing a nasal spray pharmaceutical formulation, wherein: the nasal spray pharmaceutical formulation has a volume between about 100 μL and about 140 μL and consists of about 3 mg/mL, about 4 mg/mL, about 5 mg/mL, about 6 mg/mL, about 7 mg/mL, about 8 mg/mL, about 9 mg/mL, about 10 mg/mL, about 11 mg/mL, about 12 mg/mL, about 13 mg/mL, about 14 mg/mL, about 15 mg/mL, about 16 mg/mL, about 17 mg/mL, about 18 mg/mL, about 19 mg/mL, or about 20 mg/mL of epinephrine; water; between about 0.15% (w/v) and about 0.35% (w/v) of dodecyl maltoside; between about 0.2% (w/v) and about 1.2% (w/v) of sodium chloride; ethylenediaminetetraacetic acid (EDTA) or disodium salt thereof; between about 0.001% (w/v) and about 0.2% (w/v) of benzalkonium chloride; optionally sodium metabisulfite; and hydrochloric acid, sodium hydroxide, or both hydrochloric acid and sodium hydroxide, to adjust the pH to a final pH between about 3.0 and about 5.0; and wherein one actuation of the nasal spray device delivers about 100 μL of the nasal spray pharmaceutical formulation into one nostril of a human. 9. The nasal spray device of claim 8, wherein: the nasal spray pharmaceutical formulation consists of about 10 mg/mL, about 11 mg/mL, about 12mg/mL, about 13 mg/mL, about 14 mg/mL, about 15 mg/mL, about 16 mg/mL, about 17mg/mL, about 18 mg/mL, about 19 mg/mL, or about 20 mg/mL of epinephrine; water; between about 0.15% (w/v) and about 0.35% (w/v) of dodecyl maltoside; between about 0.2% (w/v) and about 1.2% (w/v) of sodium chloride; ethylenediaminetetraacetic acid (EDTA) or disodium salt thereof; between about 0.001% (w/v) and about 0.2% (w/v) of benzalkonium chloride; optionally sodium metabisulfite; and hydrochloric acid, sodium hydroxide, or both hydrochloric acid and sodium hydroxide to adjust the pH to a final pH between about 3.0 and about 5.0. 10. The nasal spray device of claim 8, wherein: the nasal spray pharmaceutical formulation consists of about 10 mg/mL of epinephrine; water; about 0.25% (w/v) dodecyl maltoside; about 0.9% (w/v) of sodium chloride; disodium salt of ethylenediaminetetraacetic acid (EDTA); about 0.04% (w/v) of benzalkonium chloride; sodium metabisulfite; and hydrochloric acid, sodium hydroxide, or both hydrochloric acid and sodium hydroxide to adjust the pH to a final pH between about 3.0 and about 5.0. 11. The nasal spray device of claim 8, wherein: the nasal spray pharmaceutical formulation consists of about 20 mg/mL of epinephrine; water; about 0.25% (w/v) dodecyl maltoside; about 0.9% (w/v) of sodium chloride; disodium salt of ethylenediaminetetraacetic acid (EDTA); about 0.04% (w/v) of benzalkonium chloride; sodium metabisulfite; and hydrochloric acid, sodium hydroxide, or both hydrochloric acid and sodium hydroxide to adjust the pH to a final pH between about 3.0 and about 5.0.