High-pressure suction device

Abstract

The present invention relates to the field of inhalation devices for medically active liquids. In particular, it relates to an inhalation device that delivers particularly high pressure for nebulization. The inhalation device comprises a housing (1), a reservoir (2), a pump unit (3) connected to a means for delivering mechanical energy (4) to the pump unit (3), and a nozzle (5). The pump unit (3) comprises a hollow cylindrical part (3A) and a piston (3B). The cylindrical part (3A) has an interior space (3C) with a defined first cross section (A1) configured to receive the upstream end (3B') of the piston (3B). The cylindrical part (3A) and the piston (3B) are linearly movable relative to each other to form a pump chamber with a variable volume. According to the present invention, the means for delivering mechanical energy (4) is pressurized gas, and the device comprises a pressure chamber (6) having an internal volume for holding the pressurized gas, the walls of the pressure chamber (6) being provided by a plunger (7) configured to perform a reciprocating linear motion so as to vary the internal volume of the pressure chamber (6), the plunger (7) being mechanically coupled to the piston (3B) or cylindrical portion (3A), the plunger (7) presenting a cross section (A2) greater than the cross section (A1) of the pump chamber.Furthermore, a method for generating an aerosol of a medically active liquid by an inhalation device is disclosed. [Selected Figure] Figure 1

Description

[Technical Field]

[0001] The present invention relates to the field of inhalation devices for medically active liquids, in particular to inhalation devices that deliver particularly high pressures for nebulization. [Background technology]

[0002] Nebulizers and other aerosol generators for liquids have long been known in the art. Among other things, such devices are used in medicine and therapy. In medicine and therapy, they function as inhalation devices for administering active ingredients in the form of aerosols, i.e., small droplets embedded in a gas. Such inhalation devices are known, for example, from U.S. Pat. No. 5,623,999. The essential components of such inhalation devices are a reservoir containing the liquid to be aerosolized, a pump unit for generating a sufficiently high pressure for atomization, and an atomizing device in the form of a nozzle.

[0003] An improvement to such an inhalation device is disclosed in US Pat. No. 5,699,499, filed by the same applicant as the present invention, the contents of which are incorporated herein in their entirety.

[0004] Depending on the specific application, the volume of nebulized liquid per dose is typically in the range of approximately 15 μl for currently available soft mist inhaler devices, although delivery of larger volumes, up to 250 μl per dose, would be desirable. Even conventional propellant-driven metered-dose inhalers are only suitable for delivering doses of up to 50–80 μl per actuation. One potential solution is to repeat the administration cycle one or more times, so that a single dose is delivered over two or more consecutive device actuations. However, this increases the release time, which is further increased by the additional time required to refill the device's pump chamber. Furthermore, repeated, reproducible actuation of the device by the user can be problematic, especially for active ingredients that must be effective immediately, such as asthma medications. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] European Patent No. 0 627 230 [Patent Document 2] International Application No. PCT / EP2018 / 061056 Summary of the Invention [Problem to be solved by the invention]

[0006] The object of the present invention is to provide a device which avoids the drawbacks of the known art. The device must be capable of releasing a large amount of medically active liquid in a sufficiently short time, in just one administration cycle. [Means for solving the problem]

[0007] In a first aspect, the present invention provides an inhalation device for generating an aerosol of a medically active liquid, comprising: The device comprises a housing (1), a reservoir (2) within the housing (1) for storing a medically active liquid, a pump unit (3) downstream of the reservoir (2) for generating pressure, connected to means for delivering mechanical energy (4) to the pump unit (3), and a nozzle (5) downstream of the pump unit (3), the pump unit (3) comprises a hollow cylindrical portion (3A) and a piston (3B), the cylindrical portion (3A) having an interior space (3C) with a defined first cross section (A1) configured to receive an upstream end (3B') of the piston (3B), the cylindrical portion (3A) and the piston (3B) being linearly movable relative to each other to form a pump chamber having a variable volume; the means for delivering mechanical energy (4) is pressurized gas, the inhalation device comprises a pressure chamber (6) having an internal volume for holding the pressurized gas, the walls of the pressure chamber (6) being provided by a plunger (7) configured to perform a reciprocating linear motion so as to vary the internal volume of the pressure chamber (6); The plunger (7) is mechanically coupled to the piston (3B) or the cylindrical portion (3A) of the pump unit (3), An inhalation device is provided in which the plunger (7) presents a cross section (A2) that is larger than the cross section (A1) of the pump chamber.

[0008] In a second aspect, the present invention provides a method for generating an aerosol of a liquid by means of an inhalation device according to the first aspect of the invention, the method comprising: - during the filling stage, providing a negative gauge pressure in the pump chamber by increasing the volume of the pump chamber, thereby - filling the pump chamber with liquid from the reservoir (2) by negative gauge pressure; - in the discharge stage, providing a positive gauge pressure in the pressure chamber (6) having a second cross section (A2), whereby - causing the plunger (7) to move; - mechanically transmitting motion to the piston (3B) or cylindrical part (3A) so as to reduce the volume of the pump chamber and generate a positive pressure in its internal space, thereby - expelling the medically active liquid from the pump chamber through a nozzle (5), whereby the pressure in the pressure chamber (6) is amplified. DETAILED DESCRIPTION OF THE INVENTION

[0009] 1. An inhalation device for generating an aerosol of a medically active liquid, comprising: The device comprises a housing (1), a reservoir (2) within the housing (1) for storing a medically active liquid, a pump unit (3) downstream of the reservoir (2) for generating pressure, connected to means for delivering mechanical energy (4) to the pump unit (3), and a nozzle (5) downstream of the pump unit (3), the pump unit (3) comprises a hollow cylindrical portion (3A) and a piston (3B), the cylindrical portion (3A) having an interior space (3C) with a defined first cross section (A1) configured to receive an upstream end (3B') of the piston (3B), the cylindrical portion (3A) and the piston (3B) being linearly movable relative to each other to form a pump chamber having a variable volume; the means for delivering mechanical energy (4) is pressurized gas, the inhalation device comprises a pressure chamber (6) having an internal volume for holding the pressurized gas, the walls of the pressure chamber (6) being provided by a plunger (7) configured to perform a reciprocating linear motion so as to vary the internal volume of the pressure chamber (6); The plunger (7) is mechanically coupled to the piston (3B) or the cylindrical portion (3A) of the pump unit (3), The object is solved by a suction device in which the plunger (7) presents a cross section (A2) that is larger than the cross section (A1) of the pump chamber.

[0010] Advantageous embodiments are set forth in the respective dependent claims, the subsequent description and the accompanying drawings.

[0011] The inhalation device is suitable for generating aerosols from medically active liquids for inhalation therapy. In particular, the inhalation device is adapted for generating and releasing dose-by-dose nebulized aerosols suitable for pulmonary delivery of medically active ingredients. The term medically active liquid as used herein also includes medically active fluids.

[0012] Typically, such an inhalation device comprises a housing and a reservoir for storing a liquid, such as a medically active liquid, within the housing. The reservoir may have a capacity for storing a liquid volume of, for example, about 1 to about 50 ml, or about 5 to about 15 ml. The device comprises a pump unit downstream of the reservoir, preferably based on the piston or plunger pump principle, and a nozzle downstream of the pump unit. Obviously, the pump unit is fluidly connected to both the nozzle and the reservoir.

[0013] The pump unit, which serves to generate the pressure, is connected to or driven by a means for delivering mechanical energy to the pump unit. By this means, the pump unit is supplied with a predefined, relatively constant peak amount of mechanical energy sufficient to generate the required discharge pressure, typically in the range of about 30 bar to about 300 bar, as described in further detail below. As a result, the discharge or delivery performance of the device is highly reproducible compared to devices in which the discharge pressure is supplied manually by the user and therefore varies significantly during the discharge phase.

[0014] More specifically, the pump unit typically includes a hollow cylindrical portion having an internal space with a volume ranging from about 1 μl to about 500 μl, or from about 5 μl to about 250 μl. Note that the term "cylindrical portion" refers to a part having a cylindrical inner surface, and that the outside and the portion not in contact with the riser pipe and / or the seal do not have to be cylindrical.

[0015] The pump unit further includes a piston. The interior space of the cylindrical portion has a defined cross-section (hereinafter also referred to as the "first" cross-section) and is configured to receive the upstream end of the piston. It is clear that the cross-section of the piston must substantially match the cross-section of the interior space. If the interior space actually has a wider cross-section, only the portion of the cross-section that matches the cross-section of the piston is used in this definition of "first cross-section." Therefore, alternatively, the cross-section of the piston can also be used to further describe the present invention.

[0016] Furthermore, the barrel and piston are linearly movable relative to one another to form a pumping chamber having a variable volume, so that by changing the volume, the pressure within the pumping chamber changes accordingly.

[0017] According to the present invention, the aforementioned means for delivering mechanical energy is pressurized gas.

[0018] Among other things, known devices utilize elastic springs as a means for delivering mechanical energy, which is manually loaded prior to the expulsion phase. While springs have the advantage of providing, in principle, an unlimited number of dosing cycles, the amount of mechanical energy that can be stored in such springs in a single cycle is therefore limited, as are the pressure obtainable in the pump chamber, and thus the dosage and time.

[0019] In contrast, the present invention utilizes a means by which much higher pump pressures can be delivered, and depending on the specific embodiment, pressure can also be delivered for a longer period within a pump cycle, thus allowing for a larger dose per cycle.

[0020] The device further includes a "pressure chamber" (not to be confused with the aforementioned pump chamber). This pressure chamber has an internal volume for holding pressurized gas. One wall of the pressure chamber is provided by a movable plunger configured to perform a reciprocating linear motion to vary the internal volume of the pressure chamber. In other words, the plunger is driven by an increase (or decrease) in pressure within the pressure chamber containing the pressurized gas. The higher the pressure, the greater the force acting on the plunger.

[0021] Furthermore, the plunger is mechanically coupled to the piston or barrel (depending on which of these components of the pump unit is movable). As a result, when the plunger moves, the piston or barrel moves. In other words, the plunger "drives" the piston or barrel, thus causing a change in volume (and therefore pressure) within the pump chamber.

[0022] To achieve pressure amplification, the plunger presents a (second) cross-section that is larger than the (first) cross-section of the pump chamber to which it is mechanically coupled. In this way, a "pneumatic lever" mechanism is provided that exploits the fact that force is proportional to the product of pressure and area. Due to the different areas, i.e., the first and (larger) second cross-sections, the first pressure (in the pressure chamber) is converted into a second (and higher) pressure in the pump chamber. This pressure can be advantageously used for high delivery rates and / or short delivery times.

[0023] Preferably, the ratio of the second cross section to the first cross section is greater than 2, or greater than 5, preferably greater than 10, e.g., in the range of about 10 to about 500. As a result, the pressure can be increased by more than 10 times, e.g., about 10 to about 100 times. For example, the means for supplying mechanical energy can provide pressurized gas with a pressure of 10 bar, resulting in a pressure of 100 bar in the pump chamber of the pump unit. This is particularly advantageous because such high pressures enable a long aerosol release phase, high release rates, and thereby large volumes of liquid that can be delivered per pump cycle. Another potential advantage is that liquids with viscosities higher than typical aqueous formulations can be aerosolized, such as liquids with viscosities in the range of about 1 to about 100 mPa·s (cP). Furthermore, the present invention is particularly suitable for inhalation devices exhibiting nozzles requiring high operating pressures, such as impingement nozzles. The present invention can spray an amount typically within the range of about 1 μl to about 500 μl, or about 5 μl to about 250 μl, for example about 50 μl, within a time period of 1.5 to 2.0 seconds, depending on the viscosity of the liquid and the nozzle type.

[0024] According to one embodiment, the pressurized gas is provided by a container filled with pressurized gas and / or liquefied gas. Preferably, the container contains liquefied gas, and as is commonly known, a container containing any liquefied gas (without being completely filled with liquefied gas) also contains any pressurized gaseous (non-liquid) gas in equilibrium with the liquid gas. Examples of potentially useful liquefied gases include liquefied propane, n-butane, isobutane, nitrous oxide, carbon dioxide, dimethyl ether, methyl ethyl ether, hexafluoroacetone, hydrofluoroalkanes (such as HFA134a or HFA227), or any mixture thereof. Among the preferred liquefied gases used in accordance with the present invention are liquefied propane, propane / butane mixtures, and / or nitrous oxide.

[0025] Preferably, the container is part of a replaceable cartridge, so that when the residual pressure in the container falls below a minimum threshold, the container can be removed from the housing of the inhalation device and a new cartridge can be inserted. A single cartridge can easily reach, for example, 50 to 200 cycles.

[0026] According to another embodiment, the pressurized gas is provided by a chamber that can be manually pressurized and that can temporarily hold and controllably release the pressurized gas. This means that the pressure in the pressure chamber can be manually increased, for example, by repeatedly activating a pump. Such a pump can be operated by linear and rotary motion and is preferably part of the inhalation device. The inhalation device can include means for monitoring the pressure and / or means for indicating when a sufficient volume of pressure exists to use the device. Once the required pressure is reached, the device can be used. Because the manual loading of the pressure chamber occurs before the actual administration, there is no interruption in administration, as is the case with devices known in the art that utilize a series of administration strokes.

[0027] While embodiments using a container or cartridge containing liquefied gas offer a particularly comfortable user experience, the latter embodiment, i.e., an embodiment using on-demand manually pressurized gas, is highly versatile due to its potential independence from the need for refilling, except with respect to the liquid being aerosolized, e.g., a medically active liquid. Also, the fact that the device according to the latter embodiment is in an inactivated state and does not contain pressurized components may be advantageous in that it must comply with fewer applicable regulatory requirements.

[0028] According to one embodiment, the piston is hollow. The hollow space can serve as a means for fluidly connecting the pump chamber with a nozzle or a reservoir. To this end, the downstream end of the piston can be directly or indirectly fluidly connected to a nozzle, or the upstream end of the piston may provide a direct or indirect fluid connection to a reservoir.

[0029] In another embodiment, the piston is solid. In this case, other means must be provided to provide an outlet from the pumping chamber. This can be achieved, for example, by providing one or more openings in the sidewall of the pumping chamber near the inlet connected to the reservoir that are not covered by the upstream end of the piston during any phase of the pumping cycle. The openings are then connected to a nozzle.

[0030] According to one embodiment, the piston is stationary and rigidly attached to the housing or nozzle, and the hollow cylinder is movable relative to the housing or nozzle. This embodiment can be referred to as a "movable chamber" embodiment, since most of the chamber, including the sidewall, is movable. The movement of the hollow cylinder is driven by a mechanically coupled plunger.

[0031] According to another embodiment, the hollow cylinder is stationary and rigidly attached to the housing or nozzle, and the piston is movable relative to the housing or nozzle. This embodiment can therefore be referred to as a "moving piston" embodiment. The piston movement is driven by a mechanically coupled plunger.

[0032] According to another embodiment, the barrel and the piston are movable. The relative movement of both parts relative to each other still results in the desired volume change of the pump chamber. Both parts may be movable in parallel or anti-parallel directions in response to the thrust movement of the plunger.

[0033] In one embodiment, a check valve is arranged upstream of the pump chamber to "actively" block the backflow of liquid in the direction of the reservoir. Here, the term "actively" indicates that a dedicated component is provided to prevent backflow. In contrast, "passive" means are means that function solely due to their dimensions, such as a particularly thin tube or a specially shaped outlet opening to a nozzle. In any case, measures must be taken to at least reduce this backflow.

[0034] In one embodiment, in addition to the "direct" pneumatic / hydraulic coupling described above, which utilizes differently sized pressure-bearing areas, a mechanical lever mechanism is provided to further increase the amplification effect of the ratio described above. In other words, amplification can be further increased by providing an additional mechanical lever, for example, which transfers a long, weak stroke to a short, strong stroke. Such a lever can be configured, for example, as a two-arm lever or can utilize a cam mechanism using an inclined surface as the lever means.

[0035] In another embodiment, means are provided for temporarily storing mechanical energy loadable by the forward movement of the plunger, the means being configured to effect backward movement of the plunger by unloading the stored energy.

[0036] In other words, this means (not to be confused with the aforementioned means for delivering mechanical energy, which results in an increase in pressure in the pump chamber) serves to create a vacuum or negative gauge pressure in the pump chamber so that the pump chamber is refilled with liquid from the reservoir. This is achieved by loading this means with an amount of mechanical energy during the discharge phase that is sufficient to "push" the barrel away from the piston and vice versa during the refill phase, thereby expanding the internal space of the pump chamber. This amount of energy is significantly less than the amount provided by the means for delivering mechanical energy, and therefore the energy available for administration is only slightly reduced by the loading of the means for temporarily storing mechanical energy.

[0037] In this way, the means for temporarily storing mechanical energy functions as a means for resetting the volume of the pumping chamber.

[0038] Preferably, the means for temporarily storing mechanical energy is an elastic spring, a gas spring, or a magnetic spring. The spring is arranged so that one end rests against the inner wall of the housing and the other end rests against the movable part (piston or cylindrical part). Energy is stored by compressing the spring during the discharge phase and is released again when the spring relaxes, resetting the volume of the pump chamber.

[0039] Obviously, if tension springs or the like are used, the design will need to be adjusted accordingly.

[0040] In a preferred embodiment, the nozzle of the inhalation device is selected from a nozzle type that exhibits or requires high operating pressures to atomize the liquid. For example, the nozzle may require pressures of 30 bar or more, such as 30-300 bar, or 50 bar or more, such as 50-300 bar, or 100 bar or more, such as 100-300 bar.

[0041] In one particularly advantageous embodiment, the nozzle is of the impingement type. Such nozzles are well known and rely on the collision of two or more colliding jets of liquid to produce a fine, sufficiently homogeneous spray into droplets that can be inhaled by the user. To further increase the amount of liquid that can be atomized in one cycle, the nozzle can also be provided with multiple layers of nozzle outlets, or multiple pairs of nozzle outlets in one layer.

[0042] According to another embodiment, the nozzle is of the Raleigh or swirl type.

[0043] In other embodiments, the volume of the pump chamber reaches at least 15 μl, or at least 30 μl, or at least 50 μl, or between about 100 μl and 250 μl, respectively.

[0044] In yet another embodiment, the pump unit is configured to provide a peak pressure in the pump chamber of at least 30 bar, preferably at least 100 bar, and most preferably at least 200 bar. The means for delivering mechanical energy is configured to provide a pressure in the pressure chamber of at least 10 bar, preferably at least 20 bar, and most preferably at least 50 bar. As used herein, these (peak) pressure values ​​refer to the maximum pressure in the pump chamber during a pump cycle.

[0045] Experiments have shown that this amount is sufficient to provide the user with a sufficiently large amount of atomized medically active liquid in a single dosing cycle.

[0046] In a more preferred embodiment, the pump chamber has an internal volume of at least about 50 μl, for example from about 50 μl to about 500 μl, or up to about 250 μl, and is configured to provide a peak pressure of at least about 100 bar.

[0047] In one embodiment, (i) the plunger and (ii) the piston and / or barrel are movable in parallel directions, and both component groups can be positioned next to each other, but can also be aligned with each other so that their respective directions of movement are collinear.

[0048] In one embodiment, the pressure chamber is provided by two parallel plates, such as disks, that can slide within the housing. Increasing the distance between the plates increases the volume of the pressure chamber, and vice versa. One of the plates can function as a mechanical connection or "coupling" to the pump unit. Thus, when the pressure chamber expands, the "coupling" plate preferably moves independently to decrease the volume of the pump chamber. After the release phase, the coupling plate remains in place to release the gas accumulated in the pressure chamber, while the other "pressure" plate moves to decrease (reset) the volume of the pressure chamber again. During the refill phase, both plates move in parallel, thereby expanding the volume of the pump chamber while keeping the volume of the pressure chamber constant.

[0049] The term "medically active liquid" as used herein should be understood in a broad sense and in certain embodiments refers to a liquid or liquid composition that may be useful in the treatment, stabilization or prevention of a condition, disorder or disease, particularly a pulmonary condition, disorder or disease in an animal or human, preferably a human.

[0050] In certain embodiments, the "medically active liquid" may be a compound or a mixture of compounds itself. In other specific embodiments, the medically active liquid may be a solution, suspension, or dispersion of an ingredient or active ingredient in a physiologically acceptable carrier or liquid. In even more specific embodiments, the physiologically acceptable carrier liquid may be water or an aqueous mixture comprising water and one or more additional physiologically acceptable solvents, such as ethanol, propylene glycol, or polyethylene glycol.

[0051] In more specific embodiments, the medically active liquid can be an aqueous solution of a physiologically acceptable salt, such as sodium chloride (saline). In certain embodiments, the medically active liquid used herein can be an aqueous solution of sodium chloride (saline), with typical sodium chloride concentrations ranging from about 0.5% to about 15% by weight, or from about 0.9% to about 10% by weight, or from about 2% to about 5% by weight, or about 4% by weight, e.g., about 3.0% by weight, where the concentrations refer to the weight of the final aqueous solution.

[0052] In certain embodiments, the term "medically active liquid" as used herein may refer to a medically active liquid in the form of a pharmaceutical composition comprising at least one active pharmaceutical ingredient (API), more particularly at least one inhalable active pharmaceutical ingredient. More specifically, such at least one inhalable active pharmaceutical ingredient may be selected, for example, from long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs) and inhalable glucocorticoids (ICSs), as well as analgesics and antidiabetic agents, alone or in combination with each other.

[0053] Examples of long-acting muscarinic antagonists (LAMAs) include, but are not limited to, aclidinium bromide, glycopyrronium salts such as glycopyrronium bromide, lebefenacin, tiotropium such as tiotropium bromide, umeclidinium bromide, oxitropium bromide, flutropium bromide, ipratropium bromide, trospium chloride, and tolterodine.

[0054] Examples of long-acting beta-agonists (LABAs) include, but are not limited to, albuterol, arformoterol, bambuterol, bitolterol, broxaterol, carbuterol, clenbuterol, fenoterol, formoterol, hexoprenaline, ibuterol, indacaterol, indacterol, isoetharine, isoprenaline, levosalbutamol, mabuterol, melaudrine, metaproterenol, olodaterol, orciprenaline, pirbuterol, procaterol, reproterol, rimiterol, ritodrine, salmeterol, salmefamol, soterenot, sulfonterol, tialamde, terbutaline, and terbuterol.

[0055] Examples of inhalable glucocorticoids (ICS) include, but are not limited to, prednisolone, prednisone, butixocort propionate, flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, dexamethasone, etiprednol dichloroacetate, deflazacort, etiprednol, loteprednol, RPR-106541, NS-126, and ST-26.

[0056] Additionally, the active pharmaceutical ingredient may be selected from an analgesic, such as an opioid analgesic (e.g., morphine, fentanyl) or a non-opioid analgesic (e.g., salicylic acid derivatives, e.g., acetylsalicylic acid) or a cannabinoid (e.g., tetrahydrocannabinol), an antidiabetic agent such as insulin.

[0057] The medically active liquid or liquid pharmaceutical composition that can be nebulized or aerosolized by the present inhalation device can contain at least one active pharmaceutical ingredient as described above, but can also contain mixtures of two or more active pharmaceutical ingredients that can be administered by inhalation.

[0058] Medically active liquid or pharmaceutical compositions that can be aerosolized by an inhalation device according to the present invention are preferably formulated as compositions that are suitable and adapted for inhalation use, in other words, compositions that can be nebulized or aerosolized for inhalation and that are physiologically acceptable for inhalation by the patient.

[0059] The medically active liquid or pharmaceutical composition that may be administered by the inhalation device according to this aspect of the invention, or that may be contained within the inhalation device and reservoir, may be in the form of a dispersion, e.g., a suspension having a liquid continuous phase and a solid dispersed phase, or in the form of a solution.

[0060] In a further embodiment, the medically active liquid or pharmaceutical composition as described above may optionally contain, in addition to one or more active pharmaceutical ingredients, one or more physiologically acceptable excipients suitable for inhalation use. Excipients that may be included in the composition may include, but are not limited to, one or more buffers for adjusting or controlling the pH of the solution, salts, taste-masking agents, surfactants, lipids, antioxidants, and cosolvents, such as ethanol or glycol, that may be used to enhance or improve solubility.

[0061] In certain embodiments, such medically active liquids may be essentially propellant-free.

[0062] In further specific embodiments, the medically active liquid may be an aqueous solution, in which one or more active pharmaceutical ingredients are dissolved and solubilized in a liquid carrier solution containing water. Such an aqueous solution may optionally contain one or more excipients, as described above.

[0063] In a second aspect, the present invention also relates to a method for producing an aerosol of a medically active liquid by means of an inhalation device as defined above, and in order to avoid repetition, reference is made to the description of such an inhalation device and its preferred embodiments, as well as to the medically active liquid and preferred embodiments.

[0064] The method includes the following steps that form a complete administration cycle: During the filling phase, a negative gauge pressure is provided in the pump chamber by increasing its volume. This can be generated, for example, by partially retracting the piston and / or the hollow cylinder from the other components, depending on which of these components are movable. The energy for this action is preferably provided by the aforementioned means for temporary storage of mechanical energy. The increase in volume and negative gauge pressure causes the pump chamber to fill with liquid, or more specifically, with medically active liquid from a reservoir to which the pump chamber is fluidly connected. Preferably, a collapsible bag can contain the liquid so that progressive emptying of the reservoir does not increase back pressure within the reservoir. During the next ejection phase, a positive gauge pressure is applied to the pressure chamber. It should be remembered that the pressure chamber has a second cross section that is larger than the first cross section of the pump chamber / piston. As a result, the wall / plunger is exposed to a positive pressure. -Positive gauge pressure influences the thrust movement of the plunger. The higher the pressure and the larger the second cross-sectional area, the greater the force acting on the plunger. Due to the mechanical coupling between the plunger and the pump unit, the motion is mechanically transferred or converted to the piston or the cylinder, depending on which is movable, so that the volume of the pump chamber decreases. It should be remembered that the pump chamber has an internal space of a first cross section. As a result, a positive pressure is generated within the internal space of the pump chamber. -The pressure in the pump chamber increases, causing the medically active liquid to be expelled from the pump chamber through a nozzle where the liquid is atomized.

[0065] Since the ratio of the second cross-section of the pressure chamber to the first cross-section of the interior space of the pump chamber is greater than 1, the pressure in the pressure chamber is amplified relative to the pressure in the pump chamber according to this ratio. As a result, a high delivery rate of the liquid to be atomized per actuation of the device (or per pump cycle) and / or an extended duration of aerosol release can be achieved. In particular, large volumes of liquid can nevertheless be atomized within a sufficiently short period of time, e.g., a volume of about 50 μl in 1 to 3 seconds.

[0066] In one embodiment, the pressure in the pressure chamber is provided by opening a valve to a container with pressurized gas.

[0067] Thus, according to one embodiment, the pressure in the pressure chamber is kept relatively constant during the ejection phase, and as a result, the pressure that is amplified and transmitted to the pump chamber is also constant, resulting in a more constant volumetric flow rate of the atomized liquid from the nozzle.

[0068] According to another embodiment, only at the beginning of the release phase, a short pulse of pressurized gas is released into the pressure chamber, resulting in a decrease in pressure as its volume increases.

[0069] In yet another embodiment, the pressure in the pressure chamber is provided by manually pressurizing the pressure chamber, resulting in an increase in pressure before the expulsion phase begins, and a decrease in pressure during the expulsion phase as the volume increases.

[0070] According to a preferred embodiment, following the discharge of liquid from the pump chamber due to the volume reduction, the aforementioned means for temporarily storing the mechanical energy applied during the discharge phase releases the stored energy, which again increases the internal volume of the pump chamber, thereby generating a negative gauge pressure therein and thereby refilling the pump chamber with liquid from the reservoir.

[0071] In another embodiment, the energy required to "reset" the volume of the pump chamber is supplied manually, i.e., by manually pushing the respective parts into the reset position.

[0072] While the volume of the pump chamber is "resetting," the volume of the pressure chamber is also reset to its initial (minimum) value. At the same time, the pressurized gas should be vented from the pump chamber so that a reduction in volume can be achieved with minimal effort, i.e., without having to work against high pressure to further compress already pressurized gas. Thus, in one embodiment, at the beginning of the refill phase, or between the release and refill phases, the contents of the pressure chamber are vented from the device to the external environment.

[0073] It is preferable to use a valve for this purpose, which can be opened and closed automatically and manually.

[0074] In a third aspect, the present invention relates to the use of an inhalation device according to the first aspect of the invention for administering by inhalation a medically active liquid in aerosolized form to an animal or human, preferably a human.

[0075] In a fourth aspect, the present invention relates to a method for the treatment, stabilisation or prevention of a pulmonary disease or condition (e.g. asthma or chronic obstructive pulmonary disease (COPD)) by inhalation administration of a medically active liquid, wherein the medically active liquid is generated and administered by an inhalation device according to the first aspect of the invention.

[0076] It should be noted that with regard to these aspects, all embodiments, preferred embodiments and combinations thereof described above in relation to the first and / or second aspects of the invention apply correspondingly. [Brief explanation of the drawings]

[0077] The invention will now be described with reference to the accompanying drawings.

[0078] [Figure 1] 1 is a schematic diagram of some components of one embodiment of an inhalation device. [Figure 2] FIG. 2 shows the apparatus of FIG. 1 at the end of the filling stage. [Figure 3] FIG. 2 shows the device of FIG. 1 in the release stage. [Figure 4] FIG. 2 shows the device of FIG. 1 in a refilling stage.

[0079] All drawings are not to scale, include only selected components, and are presented only at a level of detail sufficient to explain the invention. Although a functioning sample will obviously require additional components, these will be known to those skilled in the art and have been omitted here for the sake of brevity.

[0080] FIG. 1 shows a schematic diagram of some of the components of one embodiment of an inhalation device.

[0081] Depicted are the components of an inhalation device useful for generating an aerosol. Arranged inside a housing 1 is a reservoir 2 for storing a liquid F. The depicted reservoir 2 comprises a collapsible bag containing the liquid F (liquid not shown). Arranged downstream of the reservoir 2 is a pump unit 3. The pump unit 3 is connected to a means for delivering mechanical energy 4, which supplies mechanical energy 4 to the pump unit 3.

[0082] A nozzle 5 is arranged downstream of the pump unit 3. In the example shown, the nozzle 5 is of the impingement type.

[0083] As can be seen, the pump unit 3 comprises a hollow cylindrical portion 3A and (in this case) a hollow piston 3B. The hollow cylindrical portion 3A is stationary and rigidly attached to the housing 1, while the piston 3B is movable relative to the housing 1. In the embodiment shown, the plunger 7 and the piston 3B are movable in parallel directions, in fact along a straight line.

[0084] The cylindrical portion 3A has an internal space 3C with a defined first cross section A1. The cross section A1 can have any shape but is preferably circular. The internal space 3C is configured to receive the upstream end 3B' of the piston 3B. If the internal space 3C is wider, only the portion of the space 3C that actually serves to receive the piston 3B is considered. The cylindrical portion 3A and the piston 3B are linearly movable relative to each other to form a pumping chamber. Due to the possibility of linear movement, the pumping chamber has a variable volume.

[0085] According to the present invention, the means for delivering mechanical energy 4 is, as mentioned above, pressurized gas. The inhalation device comprises a pressure chamber 6 having an internal volume for holding pressurized gas. The walls of the pressure chamber 6 are provided by a plunger 7. The plunger 7 is configured to perform a reciprocating linear movement (up and down in the figure). The internal volume of the pressure chamber 6 is related to the position of the plunger, which in turn depends on the pressure within the pressure chamber. An increase in pressure results in a propulsive movement (here, upward), and a decrease in pressure results in a backward movement (here, downward).

[0086] The plunger 7 is mechanically coupled to the piston 3B and, in an embodiment not shown, can alternatively or additionally be coupled to the cylindrical portion 3A. As can be seen, the plunger 7 presents a cross section A2 that is larger than the cross section A1 of the pumping chamber. As a result, a pressure amplification is achieved, i.e. the pressure in the pumping chamber is higher than the pressure in the pressure chamber 6 by an amplification factor or ratio determined by the ratio of the cross sections A2 to A1.

[0087] In the illustrated embodiment, the pressurized gas is provided by a container 8 containing liquefied gas. Part of the gas is present in gaseous form (above the level of the liquid portion, depicted in black). A valve 9 separates the container 8 from the pressure chamber 6.

[0088] A valve 10 is further arranged in the outlet duct of the pressure chamber 6. A check valve 11 is arranged upstream of the pump chamber in order to block any possible backflow of liquid in the direction of the reservoir 2.

[0089] Means are provided for temporarily storing mechanical energy 12, in this embodiment realized by an elastic spring, which mechanical energy can be loaded by a forward (here upward) movement of the plunger 7. The means 12 is arranged and configured to unload its stored energy, thereby bringing about a backward (here downward) movement of the plunger 7 as shown below.

[0090] In this and subsequent figures, like reference numerals are used for like parts, with some references omitted in the subsequent figures for clarity, and the housing 1 is no longer shown.

[0091] Figure 2 shows the situation at the end of the filling phase, when the volumes of the pumping and pressure chambers have been reset. The piston 3B is in its most retracted position relative to the cylindrical part 3A, so the internal volume of the pumping chamber 3C is at its maximum. The plunger 7 is in its lowest position, so the volume of the pressure chamber 6 is very small or almost zero. The means for temporarily storing mechanical energy 12 is relaxed and ready to load mechanical energy.

[0092] Figure 3 shows the ejection stage. Here, valve 9 opens, allowing pressurized gas to flow from container 8 into pressure chamber 6. Plunger 7 moves in the direction of arrow 13 (here upwards), transmitting the force acting on it to piston 3B. The liquid contained in the pump chamber is thus ejected under high pressure through nozzle 5. Arrows 14 indicate two colliding liquid beams that produce the desired spray. Means 12 is compressed and therefore temporarily stores mechanical energy.

[0093] Figure 4 shows the situation during the refilling phase. Valve 10 is now open, allowing the pressurized gas to leave pressure chamber 6. Valve 9 is closed, preventing fresh gas from entering chamber 6. A negative gauge pressure forms in the pump chamber, which then refills from reservoir 2. The direction of flow is indicated by arrow 15.

[0094] The backward movement of the plunger, indicated by arrow 13, is driven by means of a temporary storage of mechanical energy 12, which releases it to the pump unit 3, more precisely to the plunger 7 connected to the piston 3B. A check valve 11 prevents the backflow of liquid from the outside into the hollow piston 3B.

[0095] The movement of the plunger 7 ends when it is in the reset position shown in Figure 2. The cycle is then completed and another cycle can start from the beginning. [Explanation of symbols]

[0096] 1. Housing 2 reservoirs 3 Pump Unit 3A Hollow cylindrical section 3B Piston 3C Internal space 4. Means for delivering mechanical energy 5 nozzles 6. Pressure Chamber 7 Plunger 8 containers 9,10 valves 11 Check valve 12 Means for temporary storage of mechanical energy 13, 14, 15 Arrows A1 First cross section A2 Second cross section F liquid

[0097] The following numbered list of items are embodiments encompassed by the present invention.

[0098] Item 1 1. An inhalation device for generating an aerosol of a medically active liquid, comprising: The device comprises a housing (1), a reservoir (2) for storing a medically active liquid within the housing (1), a pump unit (3) for generating pressure downstream of the reservoir (2) and connected to a means for delivering mechanical energy (4) to the pump unit (3), and a nozzle (5) downstream of the pump unit (3). Equipped with a pump unit (3) comprising a hollow cylindrical portion (3A) and a piston (3B), the cylindrical portion (3A) having an interior space (3C) with a defined first cross section (A1) configured to receive an upstream end (3B') of the piston (3B), the cylindrical portion (3A) and the piston (3B) being linearly movable relative to each other to form a pump chamber having a variable volume; 1. The inhalation device, wherein the means for delivering mechanical energy (4) is pressurized gas, comprises a pressure chamber (6) having an internal volume for holding the pressurized gas, the walls of the pressure chamber (6) being provided by a plunger (7) configured to perform a reciprocating linear motion so as to vary the internal volume of the pressure chamber (6), the plunger (7) being mechanically coupled to the piston (3B) or the cylindrical portion (3A), and wherein the plunger (7) presents a cross section (A2) that is larger than the cross section (A1) of the pump chamber.

[0099] Item 2 Item 1, inhalation device according to item 1, wherein the ratio is greater than 10.

[0100] Item 3 Pressurized gas - Containers filled with pressurized and / or liquefied gas (8), or - A chamber that can be manually pressurized and that can temporarily hold and controllably release pressurized gas 3. An inhalation device according to item 1 or 2, supplied by

[0101] Item 4 4. An inhalation device according to any one of items 1 to 3, wherein the piston (3B) is hollow.

[0102] Item 5 - the piston (3B) is immobile and rigidly attached to the housing (1) or the nozzle (5), and the hollow cylindrical part (3A) is movable relative to the housing (1) or the nozzle (5), or - the hollow cylindrical part (3A) is immobile and rigidly attached to the housing (1) or the nozzle (5), and the piston (3B) is movable relative to the housing (1) or the nozzle (5); An inhalation device according to any of the preceding items.

[0103] Item 6 An inhalation device according to any of the preceding items, wherein a check valve (11) is arranged upstream of the pump chamber to block the backflow of liquid in the direction of the reservoir (2).

[0104] Item 7 10. An inhalation device according to any of the preceding items, additionally provided with a mechanical lever mechanism to further increase said ratio.

[0105] Item 8 An inhalation device according to any of the preceding items, wherein means are provided for temporarily storing mechanical energy (12) that can be loaded by the forward movement of the plunger (7), and the means are configured to bring about backward movement of the plunger (7) by unloading the stored energy.

[0106] Item 9 9. The inhalation device according to item 8, wherein the means for temporarily storing mechanical energy (12) is an elastic spring, a gas spring, or a magnetic spring.

[0107] Item 10 An inhalation device according to any of the preceding items, wherein the nozzle (5) is of the collision type and / or the volume of the pump chamber is at least 30 μl, or at least 50 μl, or about 100 to about 250 μl, and the pump unit (3) is configured to provide a pressure of at least 100 bar in the pump chamber.

[0108] Item 11 An inhalation device according to any of the preceding items, wherein (i) the plunger (7) and (ii) the piston (3B) and / or the cylindrical portion (3A) are movable in parallel directions.

[0109] Item 12 - during the filling stage, providing a negative gauge pressure in the pump chamber by increasing the volume of the pump chamber, thereby - filling the pump chamber with liquid from the reservoir (2) by negative gauge pressure; - in the discharge stage, providing a positive gauge pressure in the pressure chamber (6) having a second cross section (A2), whereby - causing the plunger (7) to move; - mechanically transmitting motion to the piston (3B) or cylinder (3A) so as to reduce the volume of the pump chamber and generate positive pressure in its internal space, and thereby - expelling the medically active liquid from the pump chamber through a nozzle (5); Including, The pressure in the pressure chamber (6) is amplified. A method for producing a liquid aerosol using an inhalation device as defined in item 1.

[0110] Item 13 12. The method according to item 11, wherein the pressure in the pressure chamber (6) is supplied by opening a valve (9) to the container (8) with pressurized gas or by manually pressurizing the pressure chamber (6).

[0111] Item 14 14. The method according to item 12 or 13, wherein following the release of liquid from the pump chamber due to the decrease in volume, the means for temporarily storing the mechanical energy (12) loaded during the release phase releases the stored energy, thereby increasing the internal space of the pump chamber again, resulting in an internal negative pressure and refilling the pump chamber with medically active liquid from the reservoir (2).

[0112] Item 15 15. The method according to any of items 12 to 14, wherein at the start of the refilling phase the contents of the pressure chamber (6) are released to the atmosphere.

Claims

1. 1. An inhalation device for generating an aerosol of a medically active liquid, comprising: a housing (1), a reservoir (2) within said housing (1) for storing said medically active liquid, a pump unit (3) downstream of said reservoir (2) for generating pressure, said pump unit (3) being connected to means for delivering mechanical energy (4) to said pump unit (3), and a nozzle (5) downstream of said pump unit (3). Equipped with the pump unit (3) comprises a hollow cylindrical portion (3A) and a piston (3B), the cylindrical portion (3A) having an interior space (3C) with a defined first cross section (A1) configured to receive an upstream end (3B') of the piston (3B), the cylindrical portion (3A) being stationary and rigidly attached to the housing (1) or the nozzle (5), the piston (3B) being linearly movable relative to the housing (1) or the nozzle (5) to form a pump chamber having a variable volume; the means for delivering mechanical energy (4) is pressurized gas, the inhalation device comprises a pressure chamber (6) having an internal volume for holding the pressurized gas, the walls of the pressure chamber (6) being provided by a plunger (7) configured to perform a reciprocating linear movement so as to vary the internal volume of the pressure chamber (6); The plunger (7) is mechanically coupled to the piston (3B) of the pump unit (3); the plunger (7) presents a cross section (A2) that is larger than the cross section (A1) of the pump chamber, The piston (3B) is hollow, The suction device further comprises a check valve (11) arranged upstream of the pump chamber to block the backflow of liquid in the direction of the reservoir (2).

2. 2. Inhalation device according to claim 1, wherein the ratio of the cross section (A2) of the plunger (7) to the cross section (A1) of the pump chamber is greater than 2.

3. 2. The inhalation device of claim 1, wherein the ratio of the cross section (A2) of the plunger to the cross section (A1) of the pump chamber is greater than 10.

4. The pressurized gas a container (8) filled with pressurized and / or liquefied gas, or a chamber that can be manually pressurized and that can temporarily hold and controllably release said pressurized gas; 3. An inhalation device according to claim 1 or 2, supplied by

5. 4. An inhalation device according to claim 2 or 3, additionally provided with a mechanical lever mechanism to further increase the ratio amplification effect.

6. 6. An inhalation device according to claim 1, wherein means are provided for temporarily storing mechanical energy (12) that can be loaded by the forward movement of the plunger (7), said means being configured to bring about a backward movement of the plunger (7) by unloading the stored energy.

7. 7. Inhalation device according to claim 6, wherein said means for temporarily storing mechanical energy (12) is an elastic spring, a gas spring or a magnetic spring.

8. 8. Inhalation device according to any one of claims 1 to 7, wherein the nozzle (5) is of the impingement type.

9. 9. An inhalation device according to any one of claims 1 to 8, wherein the volume of the pump chamber reaches at least 30 μl, or at least 50 μl, or about 100 to 250 μl.

10. 10. Inhalation device according to any one of the preceding claims, wherein the pump unit (3) is configured to provide a pressure of at least 100 bar in the pump chamber.

11. (i) the plunger (7) and (ii) the piston (3B) is movable in a parallel direction; An inhalation device according to any one of claims 1 to 10.

12. - during the filling phase, providing a negative gauge pressure in the pumping chamber by increasing the volume of the pumping chamber, whereby - filling the pump chamber with liquid from the reservoir (2) by the negative gauge pressure; - during the expulsion phase, providing a positive gauge pressure in the pressure chamber (6) having the cross section (A2) of the plunger (7), whereby - causing the movement of said plunger (7); - mechanically transmitting said motion to said piston (3B) or said cylindrical part (3A) so as to reduce the volume of said pump chamber and generate a positive pressure in its internal space, and thereby - expelling said medically active liquid from said pump chamber through said nozzle (5); Including, The pressure in the pressure chamber (6) is amplified, performed by a person other than a doctor or a person under the doctor's instructions, 12. A method for producing a liquid aerosol using an inhalation device as defined in any one of claims 1 to 11.

13. 13. The method according to claim 12, wherein the pressure in the pressure chamber (6) is supplied by opening a valve (9) to a container (8) with pressurized gas or by manually pressurizing the pressure chamber (6).

14. 14. The method according to claim 12 or 13, wherein following the expulsion of liquid from the pump chamber by a decrease in its volume, the means for temporarily storing mechanical energy (12) loaded during the expulsion phase releases the stored energy, thereby increasing the internal space of the pump chamber again, resulting in a negative pressure in the internal space and refilling the pump chamber with medically active liquid from the reservoir (2).

15. 15. A method according to claim 14, wherein at the start of the refilling, the contents of the pressure chamber (6) are vented to the atmosphere.

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