Devices and methods for nebulizing fluids for inhalation

• US 7,360,536 B2
• Filed: 01/07/2003
• Issued: 04/22/2008
• Est. Priority Date: 01/07/2002
• Status: Active Grant

• Current Assignee: Novartis Pharma AG (Novartis Ag)
• Original Assignee: Aerogen, Inc. (Nektar Therapeutics)
• Inventors: Patel, Rajan, Klimowicz, Michael A.
• Primary Examiner(s): Yu; Justine R.
• Assistant Examiner(s): MATTER, KRISTEN CLARETTE
• Application Number:
  US10/338,194
• Publication Number:
  US 20030150446A1
• Time in Patent Office: 1,932 Days
• Field of Search: 128/200.14, 128/200.17, 128/200.19, 128/200.21, 128/200.22, 128/203.12, 128/203.14, 12820323- 25, 128/203.28, 202/309, 202/390, 604/48, 604/58, 604/140, 604/141, 604/264, 604/275, 239/338
• US Class Current: 128/200.14
• CPC Class Codes: A61M 11/005 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 11/007 Syringe-type or piston-type sprayers or atomisers
• CPC Class Codes: A61M 15/0065 Inhalators with dosage or measuring devices A61M15/0028 takes precedence; dosage devices incorporated in aerosol cans B65D83/52
• CPC Class Codes: A61M 15/0066 with means for varying the dose size
• CPC Class Codes: A61M 15/0085 using ultrasonics spraying or atomising liquids using ultrasonic vibrations in general B05B17/06
• CPC Class Codes: A61M 2016/0021 with a proportional output signal, e.g. from a thermistor
• CPC Class Codes: A61M 2016/0024 with an on-off output signal, e.g. from a switch
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61M 2205/583 by visual feedback
• CPC Class Codes: A61M 2205/584 having a color code
• CPC Class Codes: A61M 2205/8206 battery-operated
• CPC Class Codes: B05B 17/0646 Vibrating plates, i.e. plates being directly subjected to the vibrations, e.g. having a piezoelectric transducer attached thereto

Abstract

A nebulizer comprising an aerosol generator and a titration mechanism comprising a dosing mechanism, a screw assembly, a plunger and an actuator, wherein the dosing mechanism is rotatably mounted in the nebulizer and the plunger is mounted in the nebulizer to travel along a longitudinal axis substantially perpendicular to the plane of rotation of the dosing mechanism. The actuator is mounted to the nebulizer to travel in the direction of the longitudinal axis. The screw mechanism allows the rotation of the dosing mechanism to fix a variable distance of travel of the plunger based on the selected dose, without moving the plunger longitudinally. This allows the user to verify and if necessary correct the selected dose prior to any drug being released from the vial. Operation of the actuator causes longitudinal movement, through the screw mechanism, to the plunger. The actuator always moves a fixed distance along the longitudinal axis, while the plunger always moves a variable distance depending on rotation of the dosing mechanism to a selected dose.

Claims

1. A nebulizer comprising:

a medicine vial assembly having a tab, wherein the medical vial assembly contains a medicine fluid;

a reservoir assembly having a detent, wherein the reservoir assembly engages the medicine vial assembly in fluid communication therewith and the detent and the tab interlock to hold together the medical vial assembly and the reservoir assembly;

an aerosol generator mounted in fluid communication with the reservoir assembly; and

a titration mechanism comprising;

a plunger situated to act upon the medicine vial assembly, a screw assembly mechanically engaged with the plunger, a dose selection mechanism mechanically engaged with the screw assembly to permit a user to select an amount of medical fluid to be moved from the medical vial assembly into the reservoir assembly, and an actuator button moveably mounted to act upon the screw assembly to cause linear movement of the plunger;

wherein operation of the dose selection mechanism selectively sets the linear distance the plunger will be caused to move when the actuator button is pressed, wherein movement of the plunger causes the plunger to act upon the vial assembly in such a manner so as to displace fluid from the vial assembly into the reservoir assembly, and wherein the fluid in the reservoir assembly can be ejected from the reservoir as a mist by operation of the aerosol generator.

2. The nebulizer of claim 1 wherein the tab interlocks with the detent to prevent uncoupling and holds the vial assembly and the reservoir assembly together.

3. The nebulizer of claim 1 wherein the medicine vial assembly further comprises a collar having a plurality of tabs and the reservoir assembly comprises a plurality of detents that interlock within the tabs to hold together the vial assembly and the reservoir assembly.

4. The nebulizer of claim 3 wherein the tabs interlock with the detents to hold the vial assembly and the reservoir assembly in mutual assembly with each other.

5. The nebulizer of claim 4 wherein the tabs interlock with the detents to prevent disassembly of the vial assembly and the reservoir assembly once they are assembled together.

6. The nebulizer of claim 1 wherein the reservoir assembly comprises a reservoir and a cannula in fluid communication with the reservoir and wherein the cannula engages in fluid communication with the medicine vial assembly.

7. The nebulizer of claim 6 wherein the reservoir assembly further comprises a channel connecting the cannula with the reservoir in fluid communication.

8. The nebulizer of claim 6 further comprising a valve that opens to permit fluid to move from the medicine vial into the reservoir and closes to prevent reverse flow of fluid from the reservoir to the medicine vial.

9. The nebulizer of claim 1 wherein the medicine vial assembly comprises a moveable portion that may be moved by advancement of the plunger.

10. The nebulizer of claim 9 wherein the reservoir assembly comprises a reservoir and a cannula in fluid communication with the reservoir and wherein the cannula is received within the medicine vial assembly.

11. The nebulizer of claim 10 wherein the cannula is received within the medicine vial and wherein movement of the plunger causes fluid to move from the medicine vial through the cannula into the reservoir.

12. The nebulizer of claim 1 wherein the medicine vial assembly comprises a vial containing medicine fluid, an opening of the vial and a movable stopper situated within the opening of the vial, wherein the plunger acts on the movable stopper when the actuator button is pressed thereby moving fluid out of the medicine vial.

13. The nebulizer of claim 1 wherein the reservoir assembly permanently engages the medicine vial assembly.

14. A nebulizer comprising:

a container having a tab, wherein the container contains fluid, a reservoir having a detent, wherein the reservoir is in fluid communication with the container and the detent and the tab interlock to hold together the container and the reservoir, an aerosol generator situated to eject fluid from the reservoir as an aerosol, a dose selection mechanism permitting a user to select an amount of fluid to be moved from the container into the reservoir, an actuator moveably mounted on the nebulizer wherein operation of the actuator by a user causes the selected amount of fluid to be moved from the container into the reservoir, and a plunger moveably mounted in the nebulizer, wherein operation of the actuator moves the plunger to act upon the container, and the dose selection mechanism sets the distance of movement of the plunger.

15. The nebulizer of claim 14 further comprising a plunger moveably mounted in the nebulizer and wherein the distance of movement of the plunger is set by operation of the dose selection mechanism and the movement of the plunger is effected by operation of the actuator.

16. The nebulizer of claim 15 wherein the container comprises an opening and a moveable seal friction fit within the opening and wherein the plunger is positioned to act upon the moveable seal when the actuator is operated.

17. The nebulizer of claim 16 wherein the moveable seal is moved through the container by action of the plunger upon it.

18. The nebulizer of claim 17 wherein the container defines a longitudinal axis therein and the stopper is moved through the container in a direction parallel to the longitudinal axis.

19. The nebulizer of claim 18 wherein the actuator is moveably mounted to move in a direction substantially parallel to the longitudinal axis of the container.

20. The nebulizer of claim 18 further comprising a retainer that releasably captures the actuator when the actuator is fully moved a distance from an initial position to a predetermined actuation position.

21. The nebulizer of claim 20 further comprising a release mechanism operable to release the retainer to allow the actuator to return to an initial position from a predetermined actuation position.

22. The nebulizer of claim 21 further comprising a reset mechanism that resets a visual indicator from a selected fluid amount indication to a zero indication.

23. The nebulizer of claim 22 further wherein the release mechanism and the reset mechanism are linked together such that operation of the release mechanism causes operation of the reset mechanism to reset the visual indictor.

24. The nebulizer of claim 23 wherein the dose selection mechanism comprises an electronically operable numerical display and an electronic circuitry responsive to rotation of the knob such that rotation of the knob to select a particular distance of movement of the plunger causes the numerical display to display a value corresponding to the amount of fluid that will be displaced by a selected distance of movement of the plunger.

25. The nebulizer of claim 24 wherein the electronic circuitry is responsive to operation of the release mechanism such that operation of the release mechanism causes the numerical display to be reset to an initial numerical value.

26. The nebulizer of claim 14 wherein the dose selection mechanism comprises a knob that is rotatably mounted on the nebulizer, and the degree of rotation sets the distance of movement of the plunger and a visual indicator acted upon by rotation of the knob to provide a visual indication of the amount of fluid displaced by a selected distance of movement of the plunger.

27. The nebulizer of claim 26 wherein the visual indicator comprises a numerical display and numbers from 0 to a predetermined maximum and the numbers each correspond to the amount of fluid that will be displaced by a selected distance of movement of the plunger.

28. The nebulizer of claim 27 wherein the dose selection mechanism comprises an electronically operable numerical display and electronic circuitry responsive to rotation of the knob.

29. The nebulizer of claim 26 wherein the knob is rotatably mounted to rotate in a plane substantially perpendicular to the longitudinal axis of the container.

30. The nebulizer of claim 26 wherein the knob is rotatably mounted to rotate circumferentially with respect to the longitudinal axis of the container.

31. A method of delivering a nebulized fluid for inhalation, comprising:

providing an aerosol generator;

providing a container having a tab, wherein the container contains a fluid to be nebulized;

providing a reservoir having a detent, wherein the reservoir is in fluid communication with the container and with the aerosol generator;

interlocking the tab and the detent to hold together the container and the reservoir;

providing a plunger positioned to act upon the container in a manner to displace fluid therefrom;

providing a screw assembly operable through a range of operating positions situated to act upon the plunger to selectively limit the distance of movement of the plunger;

selecting a distance of movement of the plunger by a dose selection mechanism operating the screw assembly to a selected operating position;

providing an actuator movably mounted to act upon the screw assembly to cause linear movement of the plunger through the selected distance of movement to displace fluid from the container into the reservoir; and

operating the aerosol generator to eject fluid from the reservoir as a nebulized fluid for inhalation.

32. The method of claim 31 wherein the container defines a longitudinal axis and the plunger is moveable in a direction substantially parallel to the longitudinal axis.

33. The method of claim 32 further providing a visual indicator linked to the screw assembly such that operation of the screw assembly causes a visual indication corresponding to the distance of movement the plunger can move for a selected position of operation of the screw assembly.

34. The method of claim 33 wherein the visual indicator is one of a liquid crystal display and a light emitting diode and the visual indicator is linked to the screw assembly by an electronic circuitry such that operation of the screw assembly causes the visual indicator to display one of a range of numerical values that corresponds to the distance of movement of the plunger for a selected position of operation of the screw assembly.

35. The method of claim 34 wherein each of the numerical values corresponds to a precalculated fluid volume to be displaced from the container by movement of the plunger a distance based on a selected position of operation of the screw assembly.

36. The method of claim 33 wherein the step of selecting a distance of movement of the of the plunger by operating the screw assembly to a selected operating position is carried out by selecting a position of operation of the screw assembly based on a displayed numerical value.

37. The method of claim 31, further comprising providing a selection knob linked to the screw assembly and a visual indicator linked to the selection knob such that operation of the selection knob causes operation of the screw assembly and operation of the visual indicator.

38. A nebulizer comprising:

a container having a tab, wherein the container contains fluid, a reservoir having a detent, wherein the reservoir is in fluid communication with the container and the detent and the tab interlock to hold together the container and the reservoir, an aerosol generator situated to eject fluid from the reservoir as an aerosol, a dose selection mechanism permitting a user to select an amount of fluid to be moved from the container into the reservoir, an actuator moveably mounted on the nebulizer wherein operation of the actuator by a user causes the selected amount of fluid to be moved from the container into the reservoir, and a plunger moveably mounted in the nebulizer, wherein the distance of movement of the plunger is set by operation of the dose selection mechanism and the movement of the plunger is effected by operation of the actuator.

39. The nebulizer of claim 38 wherein the container defines a longitudinal axis therein and a stopper is moved through the container in a direction parallel to the longitudinal axis.

40. The nebulizer of claim 38 wherein the actuator is moveably mounted to move in a direction substantially parallel to a longitudinal axis of the container.

41. The nebulizer of claim 38 wherein the dose selection mechanism comprises a knob that is rotatably mounted on the nebulizer, and the degree of rotation sets the distance of movement of the plunger and a visual indicator acted upon by rotation of the knob to provide a visual indication of the amount of fluid displaced by a selected distance of movement of the plunger.

42. The nebulizer of claim 38 further comprising a visual indicator, wherein the visual indicator comprises a numerical display and numbers from 0 to a predetermined maximum and the numbers each correspond to the amount of fluid that will be displaced by a selected distance of movement of the plunger.

43. The nebulizer of claim 38 further comprising a knob rotatably mounted to rotate in a plane substantially perpendicular to a longitudinal axis of the container.

44. The nebulizer of claim 43 wherein the knob is rotatably mounted to rotate circumferentially with respect to the longitudinal axis of the container.

45. The nebulizer of claim 38 further comprising a retainer that releasably captures the actuator when the actuator is fully moved a distance from an initial position to a predetermined actuation position.

46. The nebulizer of claim 45 further comprising a release mechanism operable to release the retainer to allow the actuator to return to the initial position from the predetermined actuation position.

47. The nebulizer of claim 46 further comprising a reset mechanism that resets the visual indicator from a selected fluid amount indication to a zero indication.

48. The nebulizer of claim 47 further wherein the release mechanism and the reset mechanism are linked together such that operation of the release mechanism causes operation of the reset mechanism to reset the visual indictor.

49. A method of aerosolizing a liquid, comprising,

providing a nebulizer comprising an aerosol generator;

providing a titration mechanism in the nebulizer, the titration mechanism comprising a dosing mechanism, a screw mechanism, an actuator and a plunger, the plunger movable along a longitudinal axis within the nebulizer, the actuator movable a fixed distance X along the axis defined by the plunger and the dosing mechanism rotatable in a plane substantially perpendicular to the longitudinal axis;

providing a vial mechanism comprising a vial and a tab, the vial having a longitudinal axis and a movable seal movable along the longitudinal axis;

providing a reservoir mechanism having a detent, wherein the reservoir mechanism is in fluid communication with the vial mechanism;

interlocking the tab and the detent to hold together the vial mechanism and the reservoir mechanism;

inserting the vial mechanism into the nebulizer such that the longitudinal axis of the vial is substantially parallel to the longitudinal axis of the plunger;

rotating the dosing mechanism to select a dose,

operating the screw mechanism, by rotating the dosing mechanism, to set a variable distance Y of travel of the plunger corresponding to a selected dose without imparting longitudinal travel of the plunger;

moving the actuator longitudinally the fixed distance X to move the plunger longitudinally the selected variable distance Y;

moving a movable stopper the variable distance Y by movement of the plunger the selected variable distance Y;

displacing a volume of liquid, corresponding to the selected dose, from the vial to contact the aerosol generator; and

operating the aerosol generator to aerosolize the liquid.

50. The method of claim 49, wherein the aerosol generator comprises an aerosolization element having a first face, a second face and a plurality of apertures therethrough and wherein operating the aerosol generator comprises vibrating the aerosolization element.

51. The method of claim 49, further comprising inserting a reservoir into the nebulizer, and wherein the liquid is displaced from the vial into the reservoir.

52. The method of claim 49, wherein the nebulizer further comprises a reservoir, and wherein the liquid is displaced from the vial into the reservoir.

53. A method of nebulizing a liquid comprising:

providing a titration mechanism comprising a longitudinally moveable plunger, the movement thereof defining a longitudinal axis, a longitudinally moveable actuator to move the plunger, the movement of the actuator defining a longitudinal axis, and a screw mechanism to set the distance of travel of the plunger;

providing a rotatably mounted dosing mechanism, the rotation thereof defining an axis of rotation,

providing a vial mechanism comprising a vial defining a longitudinal access, a tab, and a moveable seal moveable along the longitudinal access of the vial;

providing a reservoir mechanism having a detent;

interlocking the tab and the detent to hold together the vial mechanism and the reservoir mechanism;

providing an aerosol generator;

controlling operation of the aerosol generator;

placing the vial mechanism within the nebulizer such that the longitudinal axis of the vial is substantially coaxial with the axis of rotation of the dosing mechanism;

rotating the dosing mechanism to select a dose;

moving the actuator to move the plunger such that fluid is dispensed from the vial; and

operating the aerosol generator to nebulize the liquid.