AEROSOL DELIVERY OF AT LEAST TWO LIQUID COMPOSITIONS

Abstract

The invention relates to the field of inhalation methods and inhalation devices for liquids. In particular, the invention relates to an inhalation method using an inhalation device adapted to separately eject at least two liquid compositions each having different properties, and to a method for the generation of an aerosol of at least two medicinal formulations by means of such inhalation device.

Claims

1. An inhalation device for the generation of an aerosol of at least two liquid compositions, the device comprising at least a first and second reservoir containing at least a first and a second liquid composition, wherein the inhalation device is a pump-actuated inhaler adapted to release upon actuation a metered dose of the first liquid composition from the first reservoir and a metered dose of the second liquid composition from the second reservoir, wherein the first and second reservoir for storing the first and second liquid composition are fluidically connected to at least a first and second pumping chamber for generation of a first pressure inside said first pumping chamber and a second pressure inside said second pumping chamber a first and second riser pipe, each of which can be received with a reservoir-facing, interior end in said first and second pumping chamber, wherein the interior volume of the first and second pumping chamber is changeable by means of relative motion of the first and second pumping chamber to the first and second riser pipe, at least a first exit area and a second exit area adapted to separately eject the first and second liquid composition from the inhalation device, a first potential energy storage unit coupled with one end of the first pumping chamber, and a second potential energy storage unit coupled with one end of the second pumping chamber.

2. The inhalation device according to claim 1, wherein the first and second pumping chamber coupled to a separate potential energy storage unit generates a desired pressure for releasing the at least two liquid compositions.

3. The inhalation device according to claim 1, wherein each of the first and second riser pipe is immobile and firmly attached to the device and/or to the first and second exit area, and each of the first and second pumping chamber is movable relative to the device and/or to the first and second exit area.

4. The inhalation device according to claim 1, wherein the first potential energy storage unit and the second potential energy storage unit each produce the same force.

5. The inhalation device according to claim 1, wherein the first potential energy storage unit and the second potential energy storage unit each produce a different force.

6. The inhalation device according to claim 4, wherein the force is about 5 newtons (N) to about 200 newtons (N).

7. The inhalation device according to claim 1, wherein the first potential energy storage unit and the second potential energy storage unit each comprise a spring.

8. (canceled)

9. The inhalation device according to claim 1, wherein the metered dose of the first liquid composition has the same volume than the metered dose of the second liquid composition.

10. The inhalation device according to claim 1, wherein the metered dose of the first liquid composition has a different volume than the metered dose of the second liquid composition.

11. The inhalation device according to claim 1, wherein the first liquid composition comprises a long-acting beta agonist and the second liquid composition comprises an inhaled corticosteroid.

12. The inhalation device according to claim 11, wherein the first liquid composition comprises a mixture of a long-acting beta agonist and a long-acting muscarinic antagonist and the second liquid composition comprises an inhaled corticosteroid.

13. (canceled)

14. (canceled)

15. (canceled)

16. The inhalation device according to claim 12, wherein the long-acting muscarinic antagonist is tiotropium bromide, the long-acting beta agonist is olodaterol, and the inhaled corticosteroid is ciclesonide.

17. (canceled)

18. (canceled)

19. The inhalation device according to claim 1, wherein the first exit area and the second exit area are incorporated into a single nozzle.

20. The inhalation device according to claim 1, wherein the first exit area is incorporated into a first nozzle and the second exit area is incorporated into a second nozzle.

21. (canceled)

22. The inhalation device according to claim 1, wherein the first reservoir and the second reservoir are incorporated into a single cartridge unit.

23. The inhalation device according to claim 1, wherein the first reservoir is incorporated into a first cartridge unit and the second reservoir is incorporated into a second cartridge unit.

24. The inhalation device according to claim 1, wherein the inhalation device is a soft-mist-inhaler.

25. The inhalation device according to claim 24, wherein the soft-mist inhaler comprises at least two impingement-type nozzles, each impingement-type nozzle having two ejection channels with two corresponding ejection trajectories, wherein the two ejection trajectories of one impingement-type nozzle have one collision point in which the two ejection trajectories intersect.

26. A method of treating or preventing a disease or condition in a subject in need thereof, the method comprising a step of administering a metered dose of a first liquid composition and a second liquid composition using an inhalation device according to claim 1.

27. (canceled)

28. (canceled)

29. A first reservoir containing a first liquid composition comprising a long-acting beta agonist and a second reservoir containing a second liquid composition comprising an inhaled corticosteroid, wherein the first and second reservoirs are adapted for use with an inhalation device according claim 1.

30. (canceled)

Description

DESCRIPTION OF THE DRAWINGS

[0089] FIG. 1 shows the main components of an inhalation device useful for carrying out the invention.

[0090] In FIG. 1, the main components of an exemplary inhalation device useful for carrying out the invention are depicted schematically and not-to-scale, at the situation prior to first use. The depicted device represents a non-limiting embodiment of the inhalation devices of the present invention disclosed herein.

[0091] The inhalation device comprises a housing 1, which is preferably shaped and dimensioned such that it can be held with one hand and can be operated by one finger, e.g., the thumb (not shown). The device further comprises two reservoirs 2A, 2B for the respective storage of a medically active liquid F1, F2. The depicted reservoirs 2A, 2B are designed to be collapsible; that means that during proceeding emptying, the elastic or at least limp walls buckle, so that the relative negative pressure (i.e., partial vacuum) which is necessary for extraction of a certain amount of liquid F1, F2 is not, or almost not, increased. A similar effect can be achieved via alternative embodiments, in which a rigid container has a movable bottom by means of which the interior volume of the respective reservoir can also be successively be reduced (not shown).

[0092] Further, the inhalation device comprises a pumping unit with two pumping chambers 3A, 3B for generation of the desired pressures which are necessary for emitting liquid F1, F2 and nebulizing the same. The pumping unit can also comprise additional components that are not depicted (push button, locking device, etc.).

[0093] At least two potential energy storage units 6A, 6B (e.g., springs) are provided, each of which is coupled with one (upwards directed) end to the pumping chambers 3A, 3B and which is supported at housing 1 (lower part of the figure).

[0094] The inhalation device further comprises at least two riser pipes 4A, 4B with at least one respective reservoir-facing, interior end 4A′, 4B′ which can be received in said pumping chambers 3A, 3B. In other words, riser pipes 4A, 4B can at least partially be pushed into pumping chambers 3A, 3B, resulting in a decrease of the interior volumes of pumping chambers 3A, 3B. The term “interior volume” describes that volume which extends from the reservoir-facing inlet of the pumping chamber 3A, 3B to the place where the interior end 4A′, 4B′ of the riser pipe 4A, 4B is located.

[0095] Preferably, in the section which serves for the reception of the riser pipes, pumping chamber 3A, 3B has section with a circular inner cross section that corresponds to the (then also) circular outside cross section of the according riser pipe section. Of course, other cross section shapes are possible as well.

[0096] Further, the inhalation device comprises two exit areas 5A, SB, each of which is connected liquid-tight to the respective exterior ends 4A″, 4B″ of riser pipes 4A, 4B. Exit areas 5A, 5B are suitable for nebulizing/atomizing liquid in a single stream or at least two streams by using the principle of two colliding liquid jets. Exit areas 5A, 5B which are depicted as an example comprises two separate nozzle units, but the exit areas 5A, 5B may also be included in one nozzle unit (not depicted). Each of the two exit areas 5A, 5B is connected to an individual pumping chamber 3A, 3B and thus, liquid reservoirs 2A, 2B. Each liquid F1, F2 has its own pumping chamber 3A, 3B in order to avoid undesired mixing.

[0097] Riser pipes 4A, 4B are designed to be immobile and firmly attached to the device. Riser pipes 4A, 4B are also firmly attached to exit areas 5A, 5B, which in turn are attached to the device as well. On the contrary, pumping chambers 3A, 3B are designed to be movable with respect to the device and exit areas 5A, 5B. The benefits of this design have already been explained; reference is made to the respective sections above.

ITEM LIST

[0098] Amongst others, the present invention relates to the following specific embodiments: [0099] 1. An inhalation device for the generation of an aerosol of at least two liquid compositions, the device comprising at least a first and second reservoir (2A, 2B) containing at least a first and a second liquid composition (F1, F2), wherein the inhalation device is a pump-actuated inhaler adapted to release upon actuation a metered dose of the first liquid composition (F1) from the first reservoir (2A) and a metered dose of the second liquid composition (F2) from the second reservoir (2B), wherein the inhalation device comprises a first and second reservoir (2A, 2B) for storing the first and second liquid composition (F1, F2) fluidically connected to at least a first and second pumping chamber (3A, 3B) for generation of a first pressure inside said first pumping chamber (3A) and a second pressure inside said second pumping chamber (3B), a first and second riser pipe (4A, 4B), each of which can be received with a reservoir-facing, interior end (4A′, 4B′) in said first and second pumping chamber (3A, 3B), wherein the interior volume of the first and second pumping chamber (3A, 3B) is changeable by means of relative motion of the first and second pumping chamber (3A, 3B) to the first and second riser pipe (4A, 4B), at least a first exit area and a second exit area (5A, 5B) adapted to separately eject the first and second liquid composition (F1, F2) from the inhalation device, a first potential energy storage unit (6A) coupled with one end of the first pumping chamber (3A), and a second potential energy storage unit (6B) coupled with one end of the second pumping chamber (3B). [0100] 2. The inhalation device according to embodiment 1, wherein the first and second pumping chamber (3A, 3B) coupled to a separate potential energy storage unit (6A, 6B) generates a desired pressure for releasing the at least two liquid compositions. [0101] 3. The inhalation device according to any one of embodiments 1 to 2, wherein each of the first and second riser pipe (4A, 4B) is immobile and firmly attached to the device and/or to the first and second exit area (5A, 5B), and each of the first and second pumping chamber (3A, 3B) is movable relative to the device and/or to the first and second exit area (5A, 5B). [0102] 4. The inhalation device according to any one of embodiments 1 to 3, wherein the first potential energy storage unit (6A) and the second potential energy storage unit (6B) each produce the same force. [0103] 5. The inhalation device according to any one of embodiments 1 to 3, wherein the first potential energy storage unit (6A) and the second potential energy storage unit (6B) each produce a different force. [0104] 6. The inhalation device according to embodiment 4 or 5, wherein the force is about 5 newtons (N) to about 200 newtons (N). [0105] 7. The inhalation device according to any one of embodiments 1 to 6, wherein the first potential energy storage unit (6A) and the second potential energy storage unit (6B) each comprise a spring. [0106] 8. The inhalation device according to claim 7, wherein each spring has the same or different spring rate (k) from about 50 newtons/meter (N/m) to about 5.000 newtons/meter (N/m). [0107] 9. The inhalation device according to any one of embodiments 1 to 8, wherein the first exit area (5A) and the second exit area (5B) are incorporated into a single nozzle. [0108] 10. The inhalation device according to any one of embodiments 1 to 8, wherein the first exit area (SA) is incorporated into a first nozzle and the second exit area (5B) is incorporated into a second nozzle. [0109] 11. The inhalation device according to any one of embodiments 1 to 10, wherein the first exit area (5A) comprises at least two channels to eject the first liquid composition (F1) from the device and the second exit area (5B) comprises at least two channels to eject the second liquid composition (F2) from the device. [0110] 12. The inhalation device according to any one of embodiments 1 to 11, wherein the first reservoir and the second reservoir are incorporated into a single cartridge unit or the first reservoir is incorporated into a first cartridge unit and the second reservoir is incorporated into a second cartridge unit. [0111] 13. The inhalation device according to any one of embodiments 1 to 12, wherein the metered dose of the first liquid composition (F1) has the same volume than the metered dose of the second liquid composition (F2). [0112] 14. The inhalation device according to any one of embodiments 1 to 12, wherein the metered dose of the first liquid composition (F1) has a different volume than the metered dose of the second liquid composition (F2). [0113] 15. The inhalation device according to any one of embodiments 1 to 14, wherein the first liquid composition (F1) and the second liquid composition (F2) comprise the same or different solvent compositions. [0114] 16. The inhalation device according to embodiment 15, wherein the first liquid composition (F1) comprises an aqueous solution and the second liquid composition (F2) comprises an organic solution or a mixture of aqueous and organic solutions. [0115] 17. The inhalation device according to embodiment 16, wherein the organic solution comprises an alcoholic solution. [0116] 18. The inhalation device according to any one of embodiments 1 to 17, wherein the first liquid composition comprises a long-acting beta agonist and the second liquid composition comprises an inhaled corticosteroid. [0117] 19. The inhalation device according to embodiment 18, wherein a metered dose of the first liquid composition comprising the long-acting beta agonist has a volume of at least 1 μL and a metered dose of the second liquid composition comprising the inhaled corticosteroid has a volume of at least 1 μL. [0118] 20. The inhalation device according to embodiment 19, wherein the metered dose of the first liquid composition comprises an amount of at least 1 μg of the long-acting beta agonist, and wherein the metered dose of the second liquid composition comprises an amount of at least 1 μg of the inhaled corticosteroid. [0119] 21. The inhalation device according to any one of embodiments 18 to 20, wherein the first liquid composition comprises a mixture of a long-acting beta agonist and a long-acting muscarinic antagonist and the second liquid composition comprises an inhaled corticosteroid. [0120] 22. The inhalation device according to embodiment 21, wherein a metered dose of the first liquid composition comprising the long-acting beta agonist and long-acting muscarinic antagonist has a volume of at least 1 μL and a metered dose of the second liquid composition comprising the inhaled corticosteroid has a volume of at least 1 μL. [0121] 23. The inhalation device according to embodiment 22, wherein the metered dose of the first liquid composition comprises an amount of at least 1 μg of the long-acting beta agonist and an amount of at least 1 μg of the long-acting muscarinic antagonist, and wherein the metered dose of the second liquid composition comprises an amount of at least 1 μg of the inhaled corticosteroid. [0122] 24. The inhalation device according to any one of embodiments 18 to 23, wherein the long-acting beta agonist is selected from the group consisting of albuterol, arformoterol, bambuterol, bitolterol, broxaterol, carbuterol, clenbuterol, fenoterol, formoterol, hexoprenaline, ibuterol, indacaterol, indacterol, isoetharine, isoprenaline levosalbutamol, mabuterol meluadrine, metaproterenol, olodaterol, orciprenaline, pirbuterol, procaterol, reproterol, rimiterol, ritodrine, salmeterol, salmefamol, soterenot, sulphonterol, tiaramde, terbutaline, and terbuterol. [0123] 25. The inhalation device according to any one of embodiments 18 to 24, wherein the long-acting beta agonist is olodaterol. [0124] 26. The inhalation device according to any one of embodiments 21 to 25, wherein long-acting muscarinic antagonist is selected from the group consisting of aclidinium bromide, glycopyrronium bromide, revefenacin, tiotropium bromide, umeclidinium bromide, oxitropium bromide, flutropium bromide, ipratropium bromide, trospium chloride, and tolterodine. [0125] 27. The inhalation device according to any one of embodiments 21 to 26, wherein long-acting muscarinic antagonist is tiotropium bromide. [0126] 28. The inhalation device according to any one of embodiments 18 to 27, wherein the inhaled corticosteroid is selected from the group consisting of prednisolone, prednisone, butixocort propionate, flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, dexamethasone, etiprednol-dichloroacetat, deflazacort, etiprednol, loteprednol, RPR-106541, NS-126, and ST-26. [0127] 29. The inhalation device according to any one of embodiments 18 to 28, wherein the inhaled corticosteroid is ciclesonide. [0128] 30. The inhalation device according to any one of embodiments 21 to 29, wherein the long-acting muscarinic antagonist is tiotropium bromide, the long-acting beta agonist is olodaterol, and the inhaled corticosteroid is ciclesonide. [0129] 31. The inhalation device according to any one of embodiments 1 to 30, wherein the first reservoir (2A) is firmly attached to the first pumping chamber (3A) and the second reservoir (2B) is firmly attached to the second pumping chamber (3B) and thus movable inside the device; or wherein the first reservoir (2A) is connected to the first pumping chamber (3A) with a first flexible element and the second reservoir (2B) is connected to the second pumping chamber (3B) with a second flexible element, and wherein the first and second reservoirs (2A, 2B) are each firmly attached to the device. [0130] 32. The inhalation device according to any one of embodiments 1 to 31, wherein each of the first liquid composition and the second liquid composition further comprises one or more excipients, buffering agents, and/or co-solvents. [0131] 33. The inhalation device according to any one of embodiments 1 to 32, for use in the treatment or prevention of disease or condition. [0132] 34. The inhalation device according to any one of embodiments 1 to 33, for use in the treatment or prevention of a lung disease or condition. [0133] 35. The inhalation device of embodiment 34, wherein the lung disease or condition is asthma or chronic obstructive pulmonary disease (“COPD”). [0134] 36. The inhalation device of any one of embodiments 18 to 35, wherein the long-acting beta agonist is dissolved in the first liquid composition, and the inhaled corticosteroid is dissolved in the second liquid composition. [0135] 37. The inhalation device of embodiment 36, wherein the first liquid composition further comprises a long-acting muscarinic antagonist dissolved in the first liquid composition. [0136] 38. A method of treating a subject suffering from a disease or condition, the method comprising a step of administering an effective amount of at least two active ingredients to said subject using a device according to any one of embodiments 1 to 37. [0137] 39. The method of embodiment 38, wherein the disease or condition is a lung disease or condition. [0138] 40. The method of according to any one of embodiments 38 to 39, wherein the at least two active ingredients comprise a long-acting beta agonist and an inhaled corticosteroid. [0139] 41. The method of embodiment 40, wherein the at least two active ingredients comprise a long-acting beta agonist, a long-acting muscarinic antagonist, and an inhaled corticosteroid. [0140] 42. The method according to any one of embodiments 39 to 41, wherein the lung disease or condition is asthma or chronic obstructive pulmonary disease (“COPD”). [0141] 43. A method of treating a subject suffering from a disease or condition, the method comprising a step of administering an effective amount of at least two liquid compositions each comprising an active ingredient to said subject using a device according to any one of embodiments 1 to 37. [0142] 44. A method for delivering at least two liquid compositions to a subject in need thereof, comprising the step of providing an inhalation device according to any one of embodiments 1 to 37 to said subject. [0143] 45. The method according to any one of embodiments 43 to 44, wherein the at least two liquid compositions comprise a long-acting beta agonist and an inhaled corticosteroid. [0144] 46. The method of embodiment 45, wherein the at least two liquid compositions comprise a first liquid composition comprising a long-acting beta agonist and a long-acting muscarinic antagonist and a second liquid composition comprising an inhaled corticosteroid. [0145] 47. A first reservoir containing a first liquid composition comprising a long-acting beta agonist and a second reservoir containing a second liquid composition comprising an inhaled corticosteroid, wherein the first and second reservoirs are adapted for use with an inhalation device according to any one of embodiments 1 to 37. [0146] 48. The reservoir of embodiment 47, wherein the first liquid composition further comprises a long-acting muscarinic antagonist.

LIST OF REFERENCES

[0147] 1 housing

[0148] 2A,2B first and second reservoirs

[0149] 3A,3B first and second pumping chambers

[0150] 4A,4B first and second riser pipes

[0151] 4A′,4B′ interior end

[0152] 4A″,4B″ exterior end

[0153] 5A,5B first exit area and second exit area

[0154] 6A,6B potential energy storage units

[0155] F1,F2 first and second liquid compositions