IP Library › Granted Patent US 12,324,852
Granted Patent B2
US 12,324,852 · App. 17/336,389 · Granted Jun 10, 2025

Administration of benzodiazepine compositions

Inventors: Steve Cartt (Hillsborough, CA); David Medeiros (Sparks, NV); Garry Thomas Gwozdz (Jim Thorpe, PA); Andrew Loxley (Brussels, BE); Mark Mitchnick (East Hampton, NY); David Hale (San Diego, CA); Edward T. Maggio (San Diego, CA)
Assignee: Neurelis, Inc.
A61K9/0043A61K9/008A61K9/08A61K9/10A61K31/355A61K31/5513A61K45/06A61K47/10A61K47/22A61K47/26
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Quick Facts
Patent No.
US 12,324,852
App. No.
17/336,389
Granted
Jun 10, 2025
Kind
B2
Abstract

The invention relates to pharmaceutical compositions comprising one or more benzodiazepine drugs for nasal administration, methods for producing and for using such compositions.

Claims (59)

1. A method of treating bouts of intermittent and stereotypic episodes of increased seizure activity in an epilepsy patient that is distinguishable from other seizures suffered by the patient comprising:

administering a single spray of 100 μL to one nasal mucosal membrane of the patient of a pharmaceutical solution consisting of:

56.47 mg of vitamin E USP +/−5%;

10 mg of diazepam;

0.25 mg of dodecyl maltoside;

10.50 mg of benzyl alcohol +/−5%, and a sufficient quantity of ethanol;

wherein administering the single spray of the pharmaceutical solution to the patient achieves 92.5% to 107.5% of the bioavailability of an equivalent dose of diazepam administered intravenously and is safe and effective in treating the bouts of intermittent and stereotypic episodes of increased seizure activity in the patient; and

wherein administering the single spray of the pharmaceutical solution to the one nasal mucosal membrane of the patient results in a treatment selected from the group consisting of a reduction in the severity of the seizure, a reduction in the probability that the patient will experience a repeat seizure, an increase in the interval between a current seizure and a next seizure in the patient, a reduction in the frequency of seizure in the patient and combinations thereof.

2. The method of claim 1 , wherein the treatment achieves 96% of the bioavailability of an equivalent dose of diazepam administered intravenously.

3. The method of claim 1 , where the treatment achieves a Tmax of about 1.5 hours.

4. The method of claim 1 , wherein the pharmaceutical solution is substantially free of water.

5. The method of claim 1 , wherein the single spray of 100 μL is administered to one nasal mucosal membrane of the patient as a single metered spray.

6. A method of treating bouts of intermittent and stereotypic episodes of increased seizure activity in an epilepsy patient that is distinguishable from other seizures suffered by the patient comprising:

administering a single spray of 100 μL of a stable pharmaceutical solution to one nasal mucosal membrane of the patient and administering a second single spray of 100 μL of the pharmaceutical solution to a second nasal mucosal membrane of the patient, the 100 μL of the pharmaceutical solution consisting of:

56.47 mg of vitamin E USP +/−5%;

7.5 mg of diazepam;

0.25 mg of dodecyl maltoside;

10.50 mg of benzyl alcohol +/−5%, and a sufficient quantity of ethanol;

wherein administering the single spray and the second single spray of the pharmaceutical solution to the patient achieves 92.5% to 107.5% of the bioavailability of an equivalent dose of diazepam administered intravenously and is safe and effective in treating the bouts of intermittent and stereotypic episodes of increased seizure activity in the patient; and

wherein administering the single spray and the second single spray of the pharmaceutical solution to the patient results in a treatment selected from the group consisting of a reduction in the severity of the seizure, a reduction in the probability that the patient will experience a repeat seizure, an increase in the interval between a current seizure and a next seizure in the patient, a reduction in the frequency of seizure in the patient and combinations thereof.

7. The method of claim 6 , wherein the treatment achieves 96% of the bioavailability of an equivalent dose of diazepam administered intravenously.

8. The method of claim 6 , where the treatment achieves a Tmax of about 1.5 hours.

9. The method of claim 6 , wherein the pharmaceutical solution is substantially free of water.

10. A method of treating bouts of intermittent and stereotypic episodes of increased seizure activity in an epilepsy patient that is distinguishable from other seizures suffered by the patient comprising:

administering as a single spray of 100 μL to one nasal mucosal membrane of the patient of a pharmaceutical solution consisting of:

56.47 mg of vitamin E USP +/−5%;

5 mg of diazepam;

0.25 mg of dodecyl maltoside;

10.50 mg of benzyl alcohol +/−5%, and a sufficient quantity of ethanol;

wherein administering the single spray of the pharmaceutical solution to the patient achieves 92.5% to 107.5% of the bioavailability of an equivalent dose of diazepam administered intravenously and is safe and effective in treating the bouts of intermittent and stereotypic episodes of increased seizure activity in the patient; and

wherein administering the single spray of the pharmaceutical solution to the patient achieves results in a treatment selected from the group consisting of a reduction in the severity of the seizure, a reduction in the probability that the patient will experience a repeat seizure, an increase in the interval between a current seizure and a next seizure in the patient, a reduction in the frequency of seizure in the patient and combinations thereof.

11. The method of claim 10 , wherein the treatment achieves 96% of the bioavailability of an equivalent dose of diazepam administered intravenously.

12. The method of claim 10 , where the treatment achieves a Tmax of about 1.5 hours.

13. The method of claim 10 , wherein the pharmaceutical solution is substantially free of water.

14. A method of treating bouts of intermittent and stereotypic episodes of increased seizure activity in an epilepsy patient that is distinguishable from other seizures suffered by the patient comprising:

administering a single spray of 100 μL of a stable pharmaceutical solution to one nasal mucosal membrane of the patient and administering a second single spray of 100 μL of the pharmaceutical solution to a second nasal mucosal membrane of the patient, the 100 μL of the pharmaceutical solution consisting of:

56.47 mg of vitamin E USP +/−5%;

10 mg of diazepam;

0.25 mg of dodecyl maltoside;

10.50 mg of benzyl alcohol +/−5%, and a sufficient quantity of ethanol;

wherein administering the single spray and the second single spray of the pharmaceutical solution to the patient achieves 92.5% to 107.5% of the bioavailability of an equivalent dose of diazepam administered intravenously and is safe and effective in treating the bouts of intermittent and stereotypic episodes of increased seizure activity in the patient;

wherein administering the single spray and the second single spray of the pharmaceutical solution to the patient results in a treatment selected from the group consisting of a reduction in the severity of the seizure, a reduction in the probability that the patient will experience a repeat seizure, an increase in the interval between a current seizure and a next seizure in the patient, a reduction in the frequency of seizure in the patient and combinations thereof.

15. The method of claim 14 , wherein the treatment achieves 96% of the bioavailability of an equivalent dose of diazepam administered intravenously.

16. The method of claim 14 , where the treatment achieves a Tmax of about 1.5 hours.

17. The method of claim 14 , wherein the pharmaceutical solution is substantially free of water.

18. The method of claim 1 , wherein administering the single spray of the pharmaceutical solution to the patient achieves 96% to 97% of the bioavailability of an equivalent dose of diazepam administered intravenously.

19. The method of claim 14 , wherein administering the single spray and the second single spray of the pharmaceutical solution to the patient achieves 96% to 97% of the bioavailability of an equivalent dose of diazepam administered intravenously.

20. The method of claim 1 , wherein administering the single spray of the pharmaceutical solution to the one nasal mucosal membrane of the patient results in treatment in less than about 5 minutes and treatment over about 24 hours.

21. The method of claim 6 , wherein administering the single spray and the second single spray of the pharmaceutical solution to the patient results in treatment in less than about 5 minutes and treatment over about 24 hours.

22. The method of claim 10 , wherein administering the single spray of the pharmaceutical solution to the patient results in treatment in less than about 5 minutes and treatment over about 24 hours.

23. The method of claim 14 , wherein administering the single spray and the second single spray of the pharmaceutical solution to the patient results in treatment in less than about 5 minutes and treatment over about 24 hours.

24. The method of claim 1 , wherein administering the single spray of the pharmaceutical solution to the one nasal mucosal membrane of the patient exhibits a half-life (t 1/2 ) of about 49.2 hours.

25. The method of claim 6 , wherein administering the single spray and the second single spray of the pharmaceutical solution to the patient exhibits a half-life (t 1/2) of about 49.2 hours.

26. The method of claim 10 , wherein administering the single spray of the pharmaceutical solution to the patient exhibits a half-life (t 1/2 ) of about 49.2 hours.

27. The method of claim 14 , wherein administering the single spray and the second single spray of the pharmaceutical solution to the patient exhibits a half-life (t 1/2 ) of about 49.2 hours.

28. The method of claim 1 , wherein dodecyl maltoside is n-dodecyl-β-D-maltoside.

29. The method of claim 6 , wherein dodecyl maltoside is n-dodecyl-β-D-maltoside.

30. The method of claim 10 , wherein dodecyl maltoside is n-dodecyl-β-D-maltoside.

31. The method of claim 14 , wherein dodecyl maltoside is n-dodecyl-β-D-maltoside.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded Nov 14, 2024
From: ORBIMED ROYALTY & CREDIT OPPORTUNITIES III, LP
To: NEURELIS, INC.; AEGIS THERAPEUTICS, LLC
Reel/Frame 069359/0921 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 13, 2021
From: CARTT, STEVE; MEDEIROS, DAVID; GWOZDZ, GARRY THOMAS; LOXLEY, ANDREW; MITCHNICK, MARK; HALE, DAVID; MAGGIO, EDWARD T.
To: HALE BIOPHARMA VENTURES, LLC
Reel/Frame 058369/0466 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 13, 2021
From: HALE BIOPHARMA VENTURES, LLC
To: NEURELIS, INC.
Reel/Frame 058369/0517 →
SECURITY INTEREST Recorded Aug 6, 2021
From: NEURELIS, INC.; AEGIS THERAPEUTICS, LLC
To: ORBIMED ROYALTY & CREDIT OPPORTUNITIES III, LP
Reel/Frame 057111/0242 →
Continuity (6)
Continuation 15470498 · Mar 27, 2017
Continuation 14527613 · Oct 29, 2014
Continuation 13495942 · Jun 13, 2012
Provisional Application 61570110 · Dec 13, 2011
Provisional Application 61497017 · Jun 14, 2011
Related Publication 20220117887A1 · Apr 21, 2022
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