Claims for Patent: 9,763,876

Summary for Patent: 9,763,876

Title:	Administration of benzodiazepine compositions
Abstract:	The invention relates to pharmaceutical compositions comprising one or more benzodiazepine drugs for nasal administration, methods for producing and for using such compositions.
Inventor(s):	Cartt; Steve (Union City, CA), Medeiros; David (South San Francisco, CA), Gwozdz; Garry Thomas (Jim Thorpe, PA), Loxley; Andrew (Philadelphia, PA), Mitchnick; Mark (East Hampton, NY), Hale; David (San Diego, CA), Maggio; Edward T. (San Diego, CA)
Assignee:	Hale Biopharma Ventures, LLC (Encinitas, CA)
Application Number:	14/527,613
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,763,876
Patent Claims:	1. A method of treating a patient with a disorder which is treatable with a benzodiazepine drug, comprising: administering to one or more nasal mucosal membranes of a patient a pharmaceutical solution for nasal administration consisting of a benzodiazepine drug, one or more natural or synthetic tocopherols or tocotrienols, or any combinations thereof, in an amount from about 30% to about 95% (w/w); ethanol and benzyl alcohol in a combined amount from about 10% to about 70% (w/w); and an alkyl glycoside. 2. The method of claim 1, wherein the natural or synthetic tocopherols or tocotrienols is Vitamin E. 3. The method of claim 1, wherein the benzodiazepine drug is selected from the group consisting of: alprazolam, brotizolam, chlordiazepoxide, clobazam, clonazepam, clorazepam, demoxazepam, diazepam, flumazenil, flurazepam, halazepam, midazolam, nordazepam, medazepam, nitrazepam, oxazepam, lorazepam, prazepam, quazepam, triazolam, temazepam, loprazolam, or any pharmaceutically-acceptable salts thereof, and any combinations thereof. 4. The method of claim 3, wherein the benzodiazepine drug is diazepam, or a pharmaceutically-acceptable salt thereof. 5. The method of claim 1, wherein the solution contains about 1 to about 20% (w/v) of benzodiazepine. 6. The method of claim 5, wherein the solution contains about 1 to about 20% (w/v) of diazepam. 7. The method of claim 1, wherein the one or more natural or synthetic tocopherols or tocotrienols are selected from the group consisting of: .alpha.-tocopherol,.beta.-tocopherol, .gamma.-tocopherol, .delta.-tocopherol, .alpha.-tocotrienol, .beta.- tocotrienol, .gamma.- tocotrienol, .delta.-tocotrienol, tocophersolan, any isomers thereof, any esters thereof, any analogs or derivatives thereof, and any combinations thereof. 8. The method of claim 1, wherein the solution contains ethanol from 1 to 25% (w/v) and benzyl alcohol from 1 to 25% (w/v). 9. The method of claim 8, wherein the benzodiazepine drug is present in the pharmaceutical solution in a concentration of from about 10 mg/mL to about 250 mg/mL. 10. The method of claim 9, wherein the benzodiazepine drug is present in the pharmaceutical solution in a concentration of from about 20 mg/mL to about 50 mg/mL. 11. The method of claim 1, wherein the one or more natural or synthetic tocopherols or tocotrienols, or any combinations thereof, is in an amount from about 45% to about 85% (w/w). 12. The method claim 11, wherein the one or more natural or synthetic tocopherols or tocotrienols, or any combinations thereof, is in an amount from about 60% to about 75% (w/w). 13. The method of claim 1, wherein the ethanol and benzyl alcohol is in a combined amount from about 15% to about 55% (w/w). 14. The method of claim 13, wherein the ethanol and benzyl alcohol is in a combined amount from about 25% to about 40% (w/w). 15. The method of claim 1, wherein the solution comprises ethanol from 10 to 22.5% (w/v) and benzyl alcohol from 7.5 to 12.5% (w/v). 16. The method of claim 1, wherein the solution is in a pharmaceutically-acceptable spray formulation. 17. The method of claim 16, wherein the benzodiazepine is administered in a therapeutically effective amount from about 1 mg to about 20 mg. 18. The method of claim 17, wherein said pharmaceutical solution is in a pharmaceutically-acceptable spray formulation having volume from about 10 .mu.L to about 200 .mu.L. 19. The method of claim 18, wherein the administration of the pharmaceutical solution comprises spraying at least a portion of the therapeutically effective amount of the benzodiazepine into at least one nostril. 20. The method of claim 18, wherein the administration of the pharmaceutical solution comprises spraying at least a portion of the therapeutically effective amount of the benzodiazepine into each nostril. 21. The method of claim 20, wherein the administration of the pharmaceutical solution comprises spraying a first quantity of the pharmaceutical solution into the first nostril, spraying a second quantity of the pharmaceutical solution into a second nostril, and optionally after a pre-selected time delay, spraying a third quantity of the pharmaceutical solution into the first nostril. 22. The method of claim 21, further comprising, optionally after a pre-selected time delay, administering at least a fourth quantity of the pharmaceutical solution to the second nostril. 23. The method of claim 21, wherein nasal administration of the pharmaceutical solution begins at any time before or after onset of symptoms of a disorder which is treatable with the pharmaceutical solution. 24. The method of claim 1, wherein the solution contains at least about 0.01% (w/w) of an alkyl glycoside. 25. The method of claim 24, wherein the solution contains about 0.01% to 1% (w/w) of an alkyl glycoside. 26. The method of claim 25, wherein the solution contains about 0.01% to 1% (w/w) of dodecyl maltoside. 27. The method of claim 1, wherein the solution consists of diazepam, vitamin E, ethanol, benzyl alcohol and dodecyl maltoside. 28. The method of claim 1, wherein the solution consists of about 56.47% (w/v) vitamin E, about 10.5% (w/v) benzyl alcohol, about 10% (w/v) diazepam, about 0.25%(w/v) dodecyl maltoside, q.s. dehydrated ethanol. 29. The method of claim 1, wherein the solution consists of diazepam, alkyl glycoside, vitamin E, ethanol, and benzyl alcohol. 30. The method of claim 1, wherein the solution consists of diazepam from 5 to 15% (w/v), dodecyl maltoside from about 0.01 to 1% (w/v) , vitamin E from 45 to 65% (w/v), ethanol from 10 to 25% (w/v) and benzyl alcohol from 5 to 15% (w/v). 31. The method of claim 1, wherein the solution consists of diazepam from 5 to 15% (w/v), dodecyl maltoside from 0.01 to 1% (w/v), vitamin E from 45 to 65% (w/v), ethanol from 10 to 25% (w/v)and benzyl alcohol from 5 to 15% (w/v). 32. The method of claim 1, wherein the solution consists of diazepam from 9 to 11% (w/v), dodecyl maltoside from 0.1 to 0.5% (w/v), vitamin E from 50 to 60% (w/v), ethanol from 15 to 22.5% (w/v) and benzyl alcohol from 7.5 to 12.5% (w/v). 33. The method of claim 1, wherein the solution consists of diazepam 10% (w/v), dodecyl maltoside from 0.15 to 0.3% (w/v), vitamin E from 50 to 60% (w/v), ethanol from 17 to 20% (w/v) and benzyl alcohol from 10 to 12% (w/v). 34. The method of claim 1, wherein said treatment achieves bioavailability that is from about 80 to 125% of that achieved with the same benzodiazepine administered intravenously. 35. The method of claim 34, wherein said treatment achieves bioavailability that is from about 90 to 110% of that achieved with the same benzodiazepine administered intravenously. 36. The method of claim 35, wherein said treatment achieves bioavailability that is from about 92.5 to 107.5% that obtained with the same benzodiazepine administered intravenously.