# US 12,599,611 B2 · Methods and compositions for treating seizure disorders in pediatric patients > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,599,611 B2 - Document ID: US12599611B2 - Status: Granted - Kind: B2 - Application number: 17/837,198 - Filed: 2022-06-10 - Published: 2022-12-22 - Granted: 2026-04-14 - Earliest claimed: 2021-06-10 - Assignees: Neurelis, Inc. - Applicants: Neurelis, Inc. - Inventors: Adrian L. Rabinowicz; Enrique J. Carrazana - Web page: https://patentgrep.com/patent/US12599611B2 ## CPC - A61K 31/5513: 1,4-Benzodiazepines, e.g. diazepam {or clozapine} - A61K 9/0043: {Nose} - A61K 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]} - A61K 9/08: Solutions {(composition of solutions A61K47/00)} - A61K 31/355: Tocopherols, e.g. vitamin E - A61K 31/7016: Disaccharides, e.g. lactose, lactulose (lactobionic acid A61K31/7032) - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61P 25/08: Antiepileptics; Anticonvulsants - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Compositions for intranasal delivery of benzodiazepines, such as diazepam, midazolam, and lorazepam and methods for their use to treat and prevent seizures in pediatric subjects aged 2-5, inclusive. Compositions for rapid therapeutic onset with a decreased incidence and/or severity of adverse effects after administration and methods of improving patient compliance with a prescribed treatment regimen. ## Claims ### Claim 1 A method of treating intermittent, stereotypic episodes of frequent seizure activity that are distinct from a subject's usual seizure pattern in a pediatric subject that is 2 to 5 years old and 23 to 33 kg in body weight having epilepsy, said method comprising: intranasally administering a pharmaceutical solution to the pediatric subject, wherein the pharmaceutical solution is one spray in each nostril of 100 μL of pharmaceutical solution having a diazepam concentration of 75 mg/mL, 0.25% w/v dodecyl maltoside, and a carrier system comprising 10.5% w/v benzyl alcohol; wherein said administering is to a nasal mucosal membrane of the pediatric subject to treat the intermittent, stereotypic episodes of frequent seizure activity that are distinct from the subject's usual seizure pattern in the pediatric subject. ### Claim 2 (depends on 1) The method of claim 1, wherein the carrier system further comprises 56.5% w/V vitamin E and an amount of ethanol sufficient to reach a volume of 100 μL. ### Claim 3 (depends on 1) The method of claim 1, wherein the pharmaceutical solution is provided in a pre-primed single use dosage device. ### Claim 4 (depends on 1) The method of claim 1, wherein said administering reduces clinical seizure activity in the pediatric subject for a period of at least 48 hours after said administering. ### Claim 5 (depends on 1) The method of claim 1, wherein said administering prevents a second seizure in the pediatric subject for a period of at least 8 hours after said administering. ### Claim 6 (depends on 1) The method of claim 1, wherein said administering prevents a second seizure in the pediatric subject for a period of at least 48 hours after said administering. ### Claim 7 (depends on 1) The method of claim 1, wherein the pediatric subject does not require a second administration of said composition within at least 24-hours of experiencing a first seizure. ### Claim 8 (depends on 1) The method of claim 1, wherein the administering is performed in a prodromal phase or pre-ictal phase of a seizure. ### Claim 9 (depends on 1) The method of claim 1, wherein the administering is performed in an ictal phase of a seizure. ### Claim 10 (depends on 1) The method of claim 1, wherein said administering achieves 96% to 97% bioavailability of an equivalent dose of intravenously administered diazepam. ### Claim 11 (depends on 1) The method of claim 1, wherein the pharmaceutical solution is self-administered by the subject. ### Claim 12 A method of treating intermittent, stereotypic episodes of frequent seizure activity that are distinct from a subject's usual seizure pattern in a pediatric subject that is 2 to 5 years old and 6 to 11 kg in body weight having epilepsy, said method comprising: intranasally administering a pharmaceutical solution to the pediatric subject, wherein the pharmaceutical solution is one spray in a single nostril of 100 μL of the pharmaceutical solution having a diazepam concentration of 50 mg/mL, 0.25% w/v dodecyl maltoside and a carrier system comprising 10.5% w/v benzyl alcohol; wherein said administering is to a nasal mucosal membrane of the pediatric subject to treat the intermittent, stereotypic episodes of frequent seizure activity that are distinct from the subject's usual seizure pattern in the pediatric subject. ### Claim 13 (depends on 12) The method of claim 12, wherein the carrier system further comprises 56.5% w/V vitamin E and an amount of ethanol sufficient to reach a volume of 100 μL. ### Claim 14 (depends on 12) The method of claim 12, wherein the pharmaceutical solution is provided in a pre-primed single use dosage device. ### Claim 15 (depends on 12) The method of claim 12, wherein said administering reduces clinical seizure activity in the pediatric subject for a period of at least 48 hours after said administering. ### Claim 16 (depends on 12) The method of claim 12, wherein said administering prevents a second seizure in the pediatric subject for a period of at least 8 hours after said administering. ### Claim 17 (depends on 12) The method of claim 12, wherein said administering prevents a second seizure in the pediatric subject for a period of at least 48 hours after said administering. ### Claim 18 (depends on 12) The method of claim 12, wherein the pediatric subject does not require a second administration of said composition within at least 24-hours of experiencing a first seizure. ### Claim 19 (depends on 12) The method of claim 12, wherein the administering is performed in a prodromal phase or pre-ictal phase of a seizure. ### Claim 20 (depends on 12) The method of claim 12, wherein the administering is performed in an ictal phase of a seizure. ### Claim 21 (depends on 12) The method of claim 12, wherein said administering achieves 96% to 97% bioavailability of an equivalent dose of intravenously administered diazepam. ### Claim 22 (depends on 12) The method of claim 12, wherein the pharmaceutical solution is self-administered by the subject. ### Claim 23 A method of treating intermittent, stereotypic episodes of frequent seizure activity that are distinct from a subject's usual seizure pattern in a pediatric subject that is 2 to 5 years old and 12 to 22 kg in body weight having epilepsy, said method comprising: intranasally administering a pharmaceutical solution to the pediatric subject, wherein the pharmaceutical solution one spray in a single nostril of 100 μL of the pharmaceutical solution having a diazepam concentration of 100 mg/mL, 0.25% w/v dodecyl maltoside and a carrier system comprising 10.5% w/v benzyl alcohol; and wherein said administering is to a nasal mucosal membrane of the pediatric subject to treat the intermittent, stereotypic episodes of frequent seizure activity that are distinct from the subject's usual seizure pattern in the pediatric subject. ### Claim 24 (depends on 23) The method of claim 23, wherein the carrier system further comprises 56.5% w/V vitamin E and an amount of ethanol sufficient to reach a volume of 100 μL. ### Claim 25 (depends on 23) The method of claim 23, wherein the pharmaceutical solution is provided in a pre-primed single use dosage device. ### Claim 26 (depends on 23) The method of claim 23, wherein said administering reduces clinical seizure activity in the pediatric subject for a period of at least 48 hours after said administering. ### Claim 27 (depends on 23) The method of claim 23, wherein said administering prevents a second seizure in the pediatric subject for a period of at least 8 hours after said administering. ### Claim 28 (depends on 23) The method of claim 23, wherein said administering prevents a second seizure in the pediatric subject for a period of at least 48 hours after said administering. ### Claim 29 (depends on 23) The method of claim 23, wherein the pediatric subject does not require a second administration of said composition within at least 24-hours of experiencing a first seizure. ### Claim 30 (depends on 23) The method of claim 23, wherein the administering is performed in a prodromal phase or pre-ictal phase of a seizure. ### Claim 31 (depends on 23) The method of claim 23, wherein the administering is performed in an ictal phase of a seizure. ### Claim 32 (depends on 23) The method of claim 23, wherein said administering achieves 96% to 97% bioavailability of an equivalent dose of intravenously administered diazepam. ### Claim 33 (depends on 23) The method of claim 23, wherein the pharmaceutical solution is self-administered by the subject.