Search

US-12616807-B2 - Medical counter measures including dry powder formulations and associated methods

US12616807B2US 12616807 B2US12616807 B2US 12616807B2US-12616807-B2

Abstract

Provided herein are dry powder formulations comprising at least one active pharmaceutical ingredient suitable for nasal application. Also provided are unit dose forms and devices comprising such formulations and methods of using such formulations for the treatment of various conditions including respiratory conditions, hemodynamic collapse, seizures, migraines, and other conditions.

Inventors

  • Scott Lyman
  • Barry Bleske

Assignees

  • Belhaven BioPharma Inc.

Dates

Publication Date
20260505
Application Date
20240520

Claims (20)

  1. 1 . A device for intranasal administration of a pharmaceutical composition comprising: a reservoir and a means for discharging one or more doses of the pharmaceutical composition, wherein the reservoir contains a quantity of the pharmaceutical composition; wherein the pharmaceutical composition is a dry powder comprising: galantamine or a pharmaceutical salt thereof, wherein the pharmaceutical composition provides a dose of about 5 mg to about 75 mg of the galantamine or the pharmaceutical salt thereof; sodium chloride, wherein the pharmaceutical composition comprises about 0.01 mg to about 5 mg of the sodium chloride; and a carrier; wherein the pharmaceutical composition does not include chitosan.
  2. 2 . The device of claim 1 , wherein the device includes a nasal probe, and wherein the nasal probe is constructed and configured to be replaced between discharges.
  3. 3 . The device of claim 1 , wherein the pharmaceutical composition further comprises a vasoactive agent, wherein the vasoactive agent is epinephrine or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition provides a dose of about 0.01 mg to about 10 mg of the epinephrine or the pharmaceutically acceptable salt thereof.
  4. 4 . The device of claim 1 , wherein the pharmaceutical composition further comprises an anti-convulsant agent, wherein the anti-convulsant agent is diazepam or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition provides a dose of about 0.1 mg to about 20 mg of the diazepam or the pharmaceutically acceptable salt thereof.
  5. 5 . The device of claim 1 , wherein the pharmaceutical composition further comprises at least one anticholinergic agent, wherein the at least one anticholinergic agent is atropine or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition provides a dose of about 0.1 mg to about 10 mg of the atropine or the pharmaceutically acceptable salt thereof.
  6. 6 . The device of claim 1 , wherein the pharmaceutical composition further comprises a cholinesterase reactivator, wherein the cholinesterase reactivator is 2-pyridine aldoxime methyl chloride or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition provides a dose of about 1 mg to about 1000 mg of the pyridine aldoxime methyl chloride or the pharmaceutically acceptable salt thereof.
  7. 7 . The device of claim 1 , wherein the pharmaceutical composition further comprises a vasodilator, wherein the vasodilator is phentolamine or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition provides a dose of about 0.01 mg to about 10 mg of the phentolamine or the pharmaceutically acceptable salt thereof.
  8. 8 . The device of claim 1 , wherein the pharmaceutical composition further comprises a catechol-o-methyl transferase (COMT) inhibitor, wherein the COMT inhibitor is entacapone or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition provides a dose of about 5 mg to about 20 mg of the entacapone or the pharmaceutically acceptable salt thereof.
  9. 9 . The device of claim 1 , wherein the pharmaceutical composition further comprises an N-Methyl-D-aspartate (NMDA) receptor antagonist, wherein the NMDA receptor antagonist is memantine, wherein the pharmaceutical composition provides a dose of about 1 mg to about 40 mg of the memantine.
  10. 10 . The device of claim 1 , wherein the pharmaceutical composition further comprises a chelator.
  11. 11 . The device of claim 1 , wherein the pharmaceutical composition further comprises one or more agents selected from a group consisting of a mucosal permeation or penetration enhancer, a mucoadhesive, a mucosal transit slowing agent, a mucosal transport enhancer, or any combination thereof.
  12. 12 . The device of claim 1 , wherein the device has 360° functionality and is constructed and configured to dispense a dose from any position.
  13. 13 . The device of claim 1 , wherein the pharmaceutical composition is a spray-dried powder.
  14. 14 . The device of claim 1 , wherein the device further includes a sensor that is adapted to detect a displacement or a deformation of a portion of the delivery device when the dose is dispensed.
  15. 15 . The device of claim 1 , wherein the device further includes a display, a power supply, a timer, a clock, and/or a printed circuit board, wherein the display is constructed and configured to display a time of dose dispensation.
  16. 16 . The device of claim 1 , wherein the device further includes a communications interface, wherein the communications interface is constructed and configured to transmit data wirelessly to at least one remote device.
  17. 17 . A kit for intranasal administration of a pharmaceutical composition comprising: at least one device, wherein each of the at least one device includes a reservoir and a means for discharging one or more doses of the pharmaceutical composition, wherein the reservoir contains a quantity of the pharmaceutical composition; and a pouch and/or a hard case; wherein the pharmaceutical composition is a dry powder comprising: galantamine or a pharmaceutical salt thereof, wherein the pharmaceutical composition provides a dose of about 5 mg to about 75 mg of the galantamine or the pharmaceutical salt thereof; sodium chloride, wherein the pharmaceutical composition comprises about 0.01 mg to about 5 mg of the sodium chloride; and a carrier; wherein the pharmaceutical composition does not include chitosan.
  18. 18 . The kit of claim 17 , wherein the hard case includes a desiccant plastic, wherein the desiccant plastic includes a base polymer, a channeling agent, and a desiccant.
  19. 19 . The kit of claim 17 , wherein the pouch and/or the hard case incorporates a pouch attachment ladder system (PALS).
  20. 20 . A device for intranasal administration of a pharmaceutical composition comprising: a reservoir and a means for discharging one or more doses of the pharmaceutical composition, wherein the reservoir contains a quantity of the pharmaceutical composition; wherein the pharmaceutical composition is a dry powder comprising: galantamine or a pharmaceutical salt thereof, wherein the pharmaceutical composition provides a dose of the galantamine or the pharmaceutical salt thereof; memantine, wherein the pharmaceutical composition provides a dose of about 1 mg to about 30 mg of the memantine; sodium chloride, wherein the pharmaceutical composition comprises about 0.01 mg to about 5 mg of the sodium chloride; and a carrier; wherein the pharmaceutical composition does not include chitosan.

Description

CROSS REFERENCES TO RELATED APPLICATIONS This application is related to and claims priority from the following U.S. patents and patent applications: this application is a continuation of U.S. application Ser. No. 18/082,311, filed on Dec. 15, 2022, which claims priority to and the benefit of U.S. Provisional Patent Application No. 63/290,948, filed Dec. 17, 2021. Each of the U.S. applications mentioned above is incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to medical counter measures, and more specifically to dry powder formulations and methods of treatment of various conditions using the dry power formulations. 2. Description of the Prior Art It is generally known in the prior art to provide medications for the treatment of various conditions. Medications are often delivered intravenously and by needle and syringe injection, which may be subcutaneous or intra-muscular. Increasingly, medications are delivered by auto-injectors, which may be used within medical facilities or in ambulatory settings by medical and non-medical personnel, caregivers, and patients themselves. Self-administration via auto-injector has dramatically improved the availability of treatment with medications in emergency situations. Alternatives that do not require a needle or syringe have been explored in the prior art. Prior art patent documents include the following: U.S. Pat. No. 10,099,019 for Nasal delivery device by inventors Shahaf, et al., filed Jan. 25, 2017 and issued Oct. 16, 2018, is directed to a method for delivering a substance to the nasal cavity of a subject in which drawing air from a mouthpiece triggers release of a substance to a subject's nasal cavities. The device comprises a container for containing the substance in fluid communication with a nosepiece, a valve with an active configuration and an inactive configuration, and a trigger mechanism to reconfigure the valve from its inactive configuration to its active configuration and vice versa. Drawing air from the mouthpiece, e.g., when the subject takes in air by mouth, activates the trigger mechanism, thereby reconfiguring the valve from its inactive configuration to its active configuration for a predetermined period of time and delivering the substance from the device to a nasal cavity of the subject. U.S. Pat. No. 10,478,574 for Nasal administration by inventors Djupesland, et al., filed Jan. 19, 2006 and issued Nov. 19, 2019, is directed to delivery device for and method of providing for delivery of substance to the central nervous system (CNS) of a subject, the delivery device including a nosepiece unit for insertion into a nasal airway of a subject and including an outlet unit which includes a nozzle for delivering substance into the nasal airway of the subject; and a substance supply unit which is operable to deliver a dose of substance to the nozzle: wherein the delivery device is configured such that at least 30% of the dose as initially deposited in the nasal airway is deposited in an upper posterior region of the nasal airway, thereby providing a CNS concentration of the substance, and hence CNS effect, which is significantly greater than that which would be predicted from a counterpart blood plasma concentration of the substance. U.S. Pat. No. 10,507,295 for Nasal drug delivery device by inventors Hoekman, et al., filed Oct. 28, 2016 and issued Dec. 17, 2019, is directed to a compound delivery device for delivering a plume derived from a propellant and a drug formulation. The drug formulation is in an intranasal dosage form in the form of powder, suspension, dispersion or liquid. The propelled intranasal dosage form is deposited within the olfactory region of the nasal cavity. The drug deposited within the olfactory region is delivered to the brain avoiding the blood-brain-barrier. Hydrofluoroalkane propellant from a pressurized canister is channeled to a diffuser and drug-containing chamber where the intra-nasal dosage form is aerosolized. The aerosolized intra-nasal dosage form passes through a nozzle thus delivering a plume to the olfactory region of a user's nasal cavity. U.S. Pat. No. 10,549,052 for Nasal delivery device by inventors Shahaf, et al., filed Feb. 28, 2013 and issued Feb. 4, 2020, is directed to a two-step mechanism for delivering a flowable substance to the nasal passages, including: a. a nosepiece adapted to be in fluid connection with said nasal passages; b. at least one air-tight enclosure, including predetermined amount of compressed gas in the same; said compressed gas is pressurized to predetermined amount of pressure; c. a charging mechanism, fluidly connected with said air-tight enclosure, characterized by at least two configurations: a retracted position and an extended position; where, when said charging mechanism is transformed from said extended position to said retracted position, said charging mechanism is adapted to enable deliver