Aerosol delivery systems, compositions and methods

• US 8,945,605 B2
• Filed: 03/14/2013
• Issued: 02/03/2015
• Est. Priority Date: 06/07/2011
• Status: Active Grant

• Current Assignee: Parion Sciences, Inc.
• Original Assignee: Parion Sciences, Inc.
• Inventors: Boucher, Paul, Boucher, Richard, Button, Brian M., Johnson, Michael R., Fink, James B., Hickey, Anthony J., Navratil, Tomas, Thelin, William Robert, Driver, Philip Jerome, Edhouse, Mark Jeffrey, Heijne, Nicholas O., Wilkins, Jonathan Hugh, Abercrombie, Stuart Robert, Taylor, Donal Joseph
• Primary Examiner(s): BARHAM, BETHANY P
• Application Number:
  US13/831,268
• Publication Number:
  US 20140109899A1
• Time in Patent Office: 691 Days
• US Class Current: 424/434
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/4965 Non-condensed pyrazines
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 38/482 Serine endopeptidases (3.4.21)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/12 Aerosols; Foams A61K9/0043, A61K9/0056, A61K9/006, A61K9/0073 take precedence; spray-films A61K9/7015
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61M 11/002 by flow deviation causing inertial separation of transported particles
• CPC Class Codes: A61M 11/003 by passing the aerosol trough sieves or filters
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 11/06 of the injector type
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 15/0086 Inhalation chambers
• CPC Class Codes: A61M 15/025 Bubble jet droplet ejection devices
• CPC Class Codes: A61M 16/0057 Pumps therefor
• CPC Class Codes: A61M 16/0666 Nasal cannulas or tubing devices for improving normal breathing through the nose A61F5/08; nose filters A62B23/06; outside holding devices A61M25/02
• CPC Class Codes: A61M 16/0672 Nasal cannula assemblies for oxygen therapy
• CPC Class Codes: A61M 16/14 by mixing different fluids, one of them being in a liquid phase
• CPC Class Codes: A61M 16/208 Non-controlled one-way valves, e.g. exhalation, check, pop-off non-rebreathing valves
• CPC Class Codes: A61M 2202/0275 : Nitric oxide [NO]
• CPC Class Codes: A61M 2205/33 : Controlling, regulating or measuring
• CPC Class Codes: A61M 2205/52 : with memories providing a history of measured variating parameters of apparatus or patient
• CPC Class Codes: A61M 2206/14 : Static flow deviators in tubes disturbing laminar flow in tubes, e.g. archimedes screws
• CPC Class Codes: A61M 2206/16 : Rotating swirling helical flow, e.g. by tangential inflows
• CPC Class Codes: C12N 15/113 : Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/14 : interfering N.A.
• CPC Class Codes: C12Y 304/21075 : Furin (3.4.21.75)
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

An aerosol preparation assembly includes an entrainment chamber defining an entrainment volume. The entrainment chamber includes a gas inlet port, an aerosol inlet port and an outlet port. The entrainment chamber is configured such that a velocity of a flow of a gas within the entrainment volume is less than a velocity of the flow of the gas within the gas inlet port. The entrainment chamber is configured such that at least a portion of inlet aerosol is entrained into the flow of the gas within the entrainment volume to produce an entrained aerosol flow at the outlet port. The particle selection chamber is configured to receive the entrained aerosol flow and produce an outlet aerosol flow. The particle selection chamber and nozzle are collectively configured such that a volumetric median diameter of the outlet aerosol flow is less than a volumetric median diameter of the inlet aerosol.

Claims

1. An apparatus comprising:

an entrainment chamber defining an entrainment volume, the entrainment chamber including a gas inlet port, an aerosol inlet port and an outlet port, the gas inlet port configured to fluidically couple a gas source to the entrainment volume, the entrainment chamber configured such that a velocity of a flow of a gas within the entrainment volume is less than a velocity of the flow of the gas within the gas inlet port, the aerosol inlet port configured to receive an inlet aerosol produced by an aerosol generator, the entrainment chamber configured such that at least a portion of the inlet aerosol is entrained into the flow of the gas within the entrainment volume to produce an entrained aerosol flow at the outlet port;

a nozzle in fluidic communication with the outlet port of the entrainment chamber, the nozzle configured to accelerate the entrained aerosol flow; and

a particle selection chamber including a cannula coupling port configured to be coupled to a nasal cannula, the particle selection chamber configured to receive the entrained aerosol flow from the nozzle and produce an outlet aerosol flow, the particle selection chamber including an obstructive structure configured to remove particles from the entrained aerosol flow such that a volumetric median diameter of the outlet aerosol flow is less than a volumetric median diameter of the inlet aerosol.

2. The apparatus of claim 1, wherein the inlet port of the entrainment chamber has an expansion ratio entering the entrainment volume of at least two.

3. The apparatus of claim 1, wherein the nozzle is monolithically constructed with at least one of the entrainment chamber or the particle selection chamber.

4. The apparatus of claim 1, wherein the entrainment chamber and the particle selection chamber are monolithically constructed.

5. The apparatus of claim 1, wherein the obstructive structure defines a tortuous path.

6. The apparatus of claim 1, wherein the obstructive structure includes a baffle, the nozzle and the baffle configured such that a portion of the entrained aerosol particles impinges on the baffle.

7. The apparatus of claim 1, further comprising at least one of the following:

a first recirculation port defined by the entrainment chamber, the first recirculation port configured to receive a rained out portion of the inlet aerosol, the first recirculation port fluidically coupled to the aerosol generator;

or

a second recirculation port defined by the particle selection chamber, the second recirculation port configured to receive a rained out portion of the entrained aerosol flow, the second recirculation port fluidically coupled to the aerosol generator.

8. The apparatus of claim 1, wherein the obstructive structure and the nozzle are collectively configured such that the volumetric median diameter of the outlet aerosol flow is substantially independent of the volumetric median diameter of the inlet aerosol.

9. The apparatus of claim 1, wherein the obstructive structure and the nozzle are collectively configured such that the volumetric median diameter of the outlet aerosol flow is between approximately one micron and approximately two microns when the volumetric median diameter of the inlet aerosol is within a range of between approximately two microns and approximately seven microns.

10. The apparatus of claim 1, wherein the obstructive structure and nozzle are collectively configured such that the volumetric median diameter of the outlet aerosol flow is between approximately one micron and approximately two microns.

11. The apparatus of claim 1, wherein the cannula coupling port includes a cannula nozzle and a coupling portion, an effective flow area of a flow path defined by an inner wall of the cannula nozzle being substantially the same as an effective flow area of a flow path defined by an inner wall of the nasal cannula, the coupling portion configured to be coupled to the nasal cannula such that the inner wall of the cannula nozzle and the inner wall of the nasal cannula form a substantially continuous surface.

12. The apparatus of claim 1, further comprising:

the gas source, the gas source configured to produce the flow of a gas within the entrainment volume having a periodic variation in flow rate.

13. The apparatus of claim 1, further comprising:

a cartridge in fluid communication with the aerosol generator, the cartridge containing a medicament from which the inlet aerosol is produced by the aerosol generator.

14. The apparatus of claim 13, wherein the medicament includes hypertonic saline.

15. An apparatus comprising:

an entrainment chamber defining an entrainment volume, the entrainment chamber including a gas inlet port, an aerosol inlet port and an outlet port, the gas inlet port configured to fluidically couple a gas source to the entrainment volume, the aerosol inlet port configured to receive an inlet aerosol produced by an aerosol generator, the entrainment chamber configured such that at least a portion of the inlet aerosol is entrained into a flow of a gas within the entrainment volume to produce an entrained aerosol flow at the outlet port; and

a particle selection chamber including a cannula coupling port configured to be coupled to a nasal cannula, the particle selection chamber configured to receive the entrained aerosol flow from the outlet port of the entrainment chamber and produce an outlet aerosol flow, the particle selection chamber including an obstructive structure configured to remove particles from the entrained aerosol flow such that a volumetric median diameter of the outlet aerosol flow is less than a volumetric median diameter of the inlet aerosol,

the cannula coupling port including a cannula nozzle and a coupling portion, the coupling portion configured to be coupled to the nasal cannula such that an inner wall of the cannula nozzle and an inner wall of the nasal cannula form a substantially continuous surface.

16. The apparatus of claim 15, further comprising:

a nozzle fluidically coupled to the outlet port of the entrainment chamber, the nozzle configured to accelerate the entrained aerosol flow between the entrainment chamber and the particle selection chamber,

the obstructive structure including a baffle, the nozzle and the baffle configured such that a portion of the entrained aerosol in the entrained aerosol flow impinges on the baffle.

17. The apparatus of claim 15, further comprising at least one of the following:

a first recirculation port defined by the entrainment chamber, the first recirculation port configured to receive a rained out portion of the inlet aerosol, the first recirculation port fluidically coupled to the aerosol generator;

or

a second recirculation port defined by the particle selection chamber, the second recirculation port configured to receive a rained out portion of the entrained aerosol flow, the second recirculation port fluidically coupled to the aerosol generator.

18. An apparatus comprising:

an entrainment chamber defining an entrainment volume, the entrainment chamber including a gas inlet port, an aerosol inlet port, and an outlet port, the gas inlet port configured to fluidically couple a gas source to the entrainment volume, the aerosol inlet port configured to receive an inlet aerosol produced by an aerosol generator, the entrainment chamber configured such that a first portion of the inlet aerosol is entrained into a flow of a gas within the entrainment volume to produce an entrained aerosol flow at the outlet port and a second portion of the inlet aerosol is collected within the entrainment chamber;

a particle selection chamber including a cannula coupling port configured to be coupled to a nasal cannula, the particle selection chamber configured to receive the entrained aerosol flow from the outlet port of the entrainment chamber and produce an outlet aerosol flow, the particle selection chamber configured to extract a portion of the entrained aerosol from the entrained aerosol flow such that a volumetric median diameter of the outlet aerosol flow is less than a volumetric median diameter of the inlet aerosol; and

a recirculation port defined by one of the entrainment chamber or the particle selection chamber, the recirculation port configured to receive one of the second portion of the inlet aerosol or the extracted portion of the entrained aerosol, the recirculation port fluidically coupled to the aerosol generator via a recirculation pathway that excludes at least one of the entrainment chamber or the particle selection chamber.

19. The apparatus of claim 18, wherein:

the outlet port includes a nozzle configured to accelerate the entrained aerosol flow between the entrainment chamber and the particle selection chamber; and

the particle selection chamber includes a baffle, the nozzle and the baffle configured such that at least a portion of the extracted portion of the entrained aerosol flow impinges on the baffle.

20. The apparatus of claim 18, wherein the cannula coupling port includes a cannula nozzle and a coupling portion, the coupling portion configured to be coupled to the nasal cannula such that an inner wall of the cannula nozzle and an inner wall of the nasal cannula form a substantially continuous surface.

21. The apparatus of claim 18, further comprising:

a cartridge in fluid communication with the aerosol generator, the cartridge containing a medicament from which the inlet aerosol is produced by the aerosol generator,

wherein the recirculation port is fluidically coupled to the cartridge.

22. The apparatus of claim 18, wherein the medicament includes hypertonic saline.

23. The apparatus of claim 18, wherein the recirculation port is a first recirculation port defined by the entrainment chamber, the recirculation pathway is a first recirculation pathway, the first recirculation port configured to receive the second portion of the inlet aerosol, the first recirculation port fluidically coupled to the aerosol generator via the first recirculation pathway that excludes the entrainment chamber, the apparatus further comprising:

a second recirculation port defined by the particle selection chamber, the second recirculation port configured to receive the extracted portion of the entrained aerosol, the second recirculation port fluidically coupled to the aerosol generator via a second recirculation pathway that excludes the particle selection chamber.

24. An apparatus comprising:

an entrainment chamber defining an entrainment volume, the entrainment chamber including a gas inlet port, an aerosol inlet port and an outlet port, the gas inlet port configured to fluidically couple a gas source to the entrainment volume, the aerosol inlet port configured to receive an inlet aerosol produced by an aerosol generator, the entrainment chamber configured such that at least a portion of the inlet aerosol is entrained into a flow of a gas within the entrainment volume to produce an entrained aerosol flow at the outlet port; and

a particle selection chamber including a cannula coupling port configured to be coupled to a nasal cannula, the particle selection chamber configured to receive the entrained aerosol flow from the outlet port of the entrainment chamber and produce an outlet aerosol flow, the particle selection chamber defining a tortuous path configured to remove particles from the entrained aerosol flow such that a volumetric median diameter of the outlet aerosol flow is less than a volumetric median diameter of the inlet aerosol.