CN117729954A

CN117729954A - Inhalation device system with counting and blocking assembly

Info

Publication number: CN117729954A
Application number: CN202280051480.7A
Authority: CN
Inventors: 尤尔根·拉威尔特; 史蒂文·杜德利; 阿尔瑙·佩尔迪戈·奥利维拉斯; 安德里亚·卡罗琳娜·赫拉斯·布里奥内斯; 朱莉娅·奥利瓦·莫雷尔; 劳拉·克洛特·卡萨库贝塔; 马克·阿利亚纳·瓜迪亚
Original assignee: Invox Belgium Co
Current assignee: Invox Belgium Co
Priority date: 2021-07-20
Filing date: 2022-07-18
Publication date: 2024-03-19

Abstract

The present invention provides an inhalation device system for inhalation administration of a medically active liquid in an aerosolized form, the system comprising an inhalation device (20) and a replaceable reservoir (30) for containing a plurality of doses of the medically active liquid, wherein a dose of the medically active liquid is dispensed from the inhalation device each time the inhalation device system is actuated, wherein the inhalation device (20) comprises: a housing (21) having a receiving unit (23) with a connection unit (24) adapted to be releasably fluidly connected to a connection port (31) of the exchangeable reservoir (30), the receiving unit (24) being adapted to receive the exchangeable reservoir (30) and to be fluidly connected to the exchangeable reservoir (30); a nozzle (25) for atomizing a medically active liquid; and a pumping unit (40) arranged within the housing (21) adapted to be fluidly connected to the exchangeable reservoir (30) and the nozzle (25), adapted to deliver a medically active liquid from the exchangeable reservoir (30) to the nozzle (25) in a downstream direction, and adapted to move the exchangeable reservoir from a rest position to an activated position upon activation of the pumping unit, wherein the inhalation device system comprises a combined counting and blocking assembly comprising: a counting unit for counting the number of actuations of the inhalation device system (after insertion of the exchangeable reservoir into the inhalation device); and a blocking unit for blocking the movement of the exchangeable reservoir from the rest position to the activated position when a defined number of actuations is reached (after insertion of the exchangeable reservoir into the inhalation device), wherein the counting unit and the blocking unit are physically separated from each other when the exchangeable reservoir is in the rest position, and the counting unit and the blocking unit are adapted to interact with each other each time the exchangeable reservoir is moved from the rest position to the activated position.

Description

Inhalation device system with counting and blocking assembly

Technical Field

The present invention relates to the field of inhalation devices for medically active liquids. In particular, the present invention relates to an inhalation device system comprising an inhalation device and a replaceable reservoir for containing a medically active liquid, wherein the inhalation device system comprises a combined counting and blocking assembly.

Background

Atomizers or other aerosol generators for liquids have long been known in the art. Such devices are used, among other things, in medicine and therapy. In this regard, they are used as inhalation devices, applying the active ingredient in the form of an aerosol (i.e. small droplets embedded in a gas). Such an inhalation device is known, for example, from document EP 0 627 230 B1. The main components of the inhalation device are: a reservoir in which a liquid to be aerosolized is contained; pumping means for generating a pressure high enough to atomize the liquid; and a spray device in the form of a nozzle. By means of a pumping device, liquid is drawn from the reservoir in discrete amounts (i.e. discontinuously) and fed to the nozzle. The pumping device works without propellant and mechanically generates pressure.

A known embodiment of such an inhalation device is described, for example, in document WO 91/14468 A1. In such devices, the pressure in a pumping chamber connected to the housing is created by the movement of a movable hollow piston. The piston is movably arranged inside a fixed cylinder or pumping chamber. An inlet disposed upstream of the hollow piston is fluidly connected to the interior of the reservoir (i.e., the reservoir tube segment). The tip arranged downstream thereof opens into the pumping chamber. Furthermore, a non-return valve is arranged inside the piston tip, which non-return valve prevents liquid from flowing back into the reservoir.

Another inhalation device is known from WO 2018/197730 A1. The hand-held inhalation device disclosed therein comprises: a housing having a user-facing side; an impingement nozzle for generating an atomized aerosol by impingement of at least two liquid jets, the nozzle being fixedly attached to a user facing side of the housing so as to be fixed relative to the housing; a fluid reservoir disposed within the housing; and a pumping unit disposed within the housing and having an upstream end fluidly connected to the fluid reservoir and a downstream end fluidly connected to the nozzle. The pumping unit is adapted to pump fluid from the fluid reservoir to the nozzle, and it comprises a stand pipe adapted to act as a piston in the pumping unit and being firmly attached to the user facing side of the housing, thereby being fixed relative to the housing.

WO 2017/076938 A1 discloses a system with a nebulizer and a container containing a fluid and an indication device for such a nebulizer. The inspection protocol is used to indicate the number of times the container has been used with the nebulizer or can still be used with the nebulizer. The indicating means indicates the number of times the current container has been used or is still usable.

WO 2019/016409 A2 discloses an atomizer for atomizing a liquid from a container and such a container. The nebulizer includes a fluid pump for drawing a dose of liquid from a container and pressurizing each dose for nebulization. The container includes an air pump having a piston/cylinder arrangement to pressurize the liquid in the container to assist in drawing the liquid from the container. The control valve limits the air pressure acting on the liquid.

These known inhalation devices or inhalation device systems typically use a counting and blocking system which typically counts the number of activations of the container and prevents further use of the nebulizer until the container is replaced. Such modular systems are typically attached to and replaced with the containers, which makes the containers more expensive to produce.

It is an object of the present invention to provide an inhalation system with a novel combined counting and blocking assembly which allows for greater flexibility when used in an inhalation device or inhalation device system.

Disclosure of Invention

A first aspect of the invention relates to an inhalation device system for inhalation administration of a medically active liquid in nebulized form,

the system comprises an inhalation device (20) and a replaceable reservoir (30) for containing a plurality of doses of a medically active liquid, wherein a dose of the medically active liquid is dispensed from the inhalation device each time the inhalation device system is actuated,

wherein the inhalation device (20) comprises:

-a housing (21) having a receiving unit (23) with a connection unit (24) adapted to be releasably fluidly connected to a connection port (31) of a replaceable reservoir (30), the receiving unit (24) being adapted to receive the replaceable reservoir (30) and to be fluidly connected to the replaceable reservoir (30);

-a nozzle (25) for atomizing a medically active liquid; and

a pumping unit (40) arranged within the housing (21) adapted to be fluidly connected to the exchangeable reservoir (30) and the nozzle (25), adapted to deliver a medically active liquid from the exchangeable reservoir (30) to the nozzle (25) in a downstream direction, and adapted to move the exchangeable reservoir from a rest position (responding position) to a priming position (priming position) upon priming of the pumping unit,

wherein the inhalation device system comprises a combined counting and blocking assembly comprising: a counting unit for counting the number of actuations of the inhalation device system (after insertion of the exchangeable reservoir into the inhalation device); and a blocking unit for blocking the movement of the exchangeable reservoir from the rest position to the activated position when a defined number of actuations is reached (after insertion of the exchangeable reservoir into the inhalation device),

wherein the counter unit and the blocking unit are physically separated from each other when the exchangeable reservoir is in the rest position, and the counter unit and the blocking unit are adapted to interact with each other each time the exchangeable reservoir is moved from the rest position to the activated position.

Drawings

Fig. 1 shows a cross-sectional view of an inhalation device system with a cartridge (cartridge) inserted into the inhalation device according to the prior art.

Figure 2 shows an exemplary embodiment of an inhalation device system according to the present invention.

Figure 3 shows a schematic view of the lower part of an inhalation device system showing the lower part of the device with a counting unit and a replaceable reservoir in the form of a container system comprising a blocking unit.

Fig. 4A, 4B and 4C show an overview of an exemplary embodiment of a counting unit.

Fig. 5A and 5B show an overview of an exemplary embodiment of a blocking unit, which is optionally attached to a replaceable reservoir.

Fig. 6A, 6B and 6C show exemplary embodiments of a counting unit and its possible interactions with a blocking unit.

Fig. 7A, 7B, 7C and 7D illustrate alternative exemplary embodiments of the counting unit.

Fig. 8A, 8B and 8C illustrate exemplary embodiments of a blocking unit and a blocking mechanism.

Detailed Description

The present invention provides an inhalation device system for the inhaled administration of a medically active liquid in an aerosolized form,

Wherein the inhalation device (20) comprises:

-a nozzle (25) for atomizing a medically active liquid; and

-a pumping unit (40) arranged within the housing (21) adapted to be fluidly connected to the exchangeable reservoir (30) and the nozzle (25), adapted to deliver a medically active liquid from the exchangeable reservoir (30) to the nozzle (25) in a downstream direction, and adapted to move the exchangeable reservoir from a rest position to an activated position upon activation of the pumping unit;

The inhalation device system according to the invention is suitable for inhaled administration of a pharmaceutically active liquid in nebulized form, wherein the term "pharmaceutically active liquid" as used herein refers to a liquid compound or composition having pharmacological activity or a liquid compound or composition comprising a compound or composition having pharmacological activity and being capable of ameliorating or preventing a symptom associated with a disease, disorder or condition, in particular a disease, disorder or condition of the respiratory system, such as a pulmonary disease, disorder or condition of a subject, in particular a warm-blooded animal or human, in particular a human. Specific examples of such diseases, disorders or conditions include, but are not limited to, pulmonary diseases or conditions such as asthma and/or Chronic Obstructive Pulmonary Disease (COPD), in particular COPD, or interstitial lung diseases affecting the lung stroma and lung tissue, such as those associated with the airways and/or the air sac (alveoli), for example, pulmonary fibrosis, such as Idiopathic Pulmonary Fibrosis (IPF), interstitial pneumonia or sarcoidosis.

Furthermore, the term "inhaled administration" as used herein refers to the route of administration as follows: wherein the medically active liquid is delivered to the respiratory system of the subject, in particular to the lower respiratory system, such as the lungs, by inhalation by the subject of an air stream or other carrier gas stream comprising the medically active liquid in atomized or aerosolized form. The terms "aerosolized", "aerosolized" or "aerosolized" as used herein synonymously refer to the state of a pharmaceutically active liquid in the form of an aerosol having at least two phases: a gaseous continuous phase, such as air or other carrier gas, comprising a dispersed liquid phase in the form of small droplets; the liquid phase, i.e. the pharmaceutically active liquid, may itself represent a liquid solution, dispersion, suspension or emulsion. In a particular embodiment, such aerosols have respirable particles or droplets, preferably having a mass median aerodynamic diameter (as measured by laser diffraction) of no greater than about 10 μm, particularly no greater than about 7 μm, or no greater than about 5 μm, respectively.

In a particular embodiment, the term "pharmaceutically active liquid" as used herein refers to a pharmaceutically active liquid in the form of a pharmaceutical composition comprising at least one Active Pharmaceutical Ingredient (API), more specifically at least one inhalable active pharmaceutical ingredient. More specifically, such at least one inhalable active pharmaceutical ingredient may be selected, for example, from the group consisting of Long Acting Muscarinic Antagonists (LAMA), long Acting Beta Agonists (LABA) and inhalable glucocorticoids (ICS), as well as analgesics and antidiabetics, which may be used alone or in combination with each other.

Examples of Long Acting Muscarinic Antagonists (LAMA) include, but are not limited to: aclidinium bromide; glycopyrronium salts such as glycopyrronium bromide; lei Fen narcissus; tiotropium, such as tiotropium bromide; turnip ammonium bromide; oxygen tropium bromide; fluotropium bromide; ipratropium bromide; trospium chloride; tolterodine.

Examples of Long Acting Beta Agonists (LABA) include, but are not limited to, salbutamol, afoterol, bambuterol, bitolterol, bromosalmeterol, carboplatin, clenbuterol, fenoterol, formoterol, hexenalin, ibuteterol, indacaterol, ethylisoprenaline, isoprenaline levosalbutamol, mabuterol Luo Meilu jun (mabuterol meluadrine), oxacinaline, odaterol, metaisoprenaline, isobutanol, procaterol, theaprocaterol, ramitretinol, ritodrine, salmeterol, sha Jiaan alcohol, soterenol, sha Fengte rol (sulphonterol), thiamide, terbutaline, terbuterol.

Examples of inhalable glucocorticoids (ICS) include, but are not limited to, prednisolone, prednisone, buticaterol propionate, flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofluminide, dexamethasone, etifool-dichloroacetic acid, deflazacort, etifool, loteprednol, RPR-106541, NS-126, ST-26.

Furthermore, the active pharmaceutical ingredient may be selected from: analgesics, such as opioid analgesics (e.g., morphine, fentanyl) or non-opioid analgesics (e.g., salicylic acid derivatives, e.g., acetylsalicylic acid) or cannabinoids (e.g., tetrahydrocannabinol); antidiabetic agents such as insulin.

The pharmaceutically active liquid or liquid pharmaceutical composition that may be nebulized or aerosolized by the present inhalation device system may comprise at least one active pharmaceutical ingredient as described above, but may also comprise a mixture of two or more active pharmaceutical ingredients that can be administered by inhalation.

The pharmaceutically active liquid or pharmaceutical composition that may be aerosolized by the inhalation device system according to the present invention is preferably formulated as a composition suitable for and suitable for inhalation use, in other words, a composition that may be nebulized or aerosolized for inhalation and physiologically acceptable for inhalation by a subject.

The pharmaceutically active liquid or pharmaceutical composition that may be administered by the present inhalation device system or may be contained in a corresponding exchangeable reservoir may be in the form of a dispersion, for example a suspension having a liquid continuous phase and a solid dispersed phase, or in the form of a solution.

In a further embodiment, a pharmaceutically active liquid or pharmaceutical composition as described above optionally comprises one or more physiologically acceptable excipients suitable for inhalation use. Excipients that may be characterized in the composition may include, but are not limited to, one or more buffers, salts, taste masking agents, surfactants, lipids, antioxidants, and co-solvents for adjusting or controlling the pH of the solution, which may be used to enhance or improve solubility, such as ethanol or ethylene glycol.

In certain embodiments, the pharmaceutically active liquid as described above may be substantially free of propellants, such as Hydrofluorocarbon (HFA) propellants.

In a further particular embodiment, the pharmaceutically active liquid as described above may be an aqueous solution, wherein one or more active pharmaceutical ingredients as described above are dissolved and dissolved in a liquid carrier solution comprising water. Such aqueous solutions may optionally further comprise one or more excipients as described above.

The inhalation device system of the present invention comprises an inhalation device and a replaceable reservoir for containing a medically active liquid. In a particular embodiment, the inhalation device of the inhalation device system of the present invention may be a hand-held device, or in other words, may be a mobile device, which may be conveniently held and used with one hand and is adapted to deliver an atomized, medically active aerosol as described above for inhalation therapy. In order to be suitable for inhalation therapy, the device must be capable of expelling a pharmaceutically active aerosol as follows: the particle size is inhalable, i.e. small enough to be absorbed by the lungs of the patient or user, with the inhalable particles being within the above-mentioned range. In this respect, inhalation devices are substantially different from devices such as those disclosed in US 2004/0068222Al which expel a spray for oral or nasal administration.

The inhalation device of the present system comprises a housing defining a housing of the inhalation device, in particular a housing accommodating and/or attaching other components of the inhalation device inside. The housing may have a user facing side that is accessible to a user of the inhalation device, in particular for inhalation administration as described above. In a particular embodiment, the user facing side may be a mouthpiece (mouthpiece) that can be introduced into the mouth of a user, in particular for inhalation or administration of an atomized medical active liquid.

Furthermore, the housing may have a lower portion, preferably at the upstream end of the inhalation device, which may be moved, opened or detached and at least partially removed to open the housing and allow access to the receiving unit into which the exchangeable reservoir may be inserted. The term "upstream" as used herein refers to the direction or location in which the inhalation device delivers the medically active liquid during operation in terms of the present inhalation device, inhalation device system, cartridge system or other components. In contrast, the term "downstream" as used herein refers to the direction or position of the inhalation device that is opposite to the direction or position in which the medically active liquid is delivered during operation.

The lower portion of the housing is preferably movable to provide access to a receiving unit as defined below. In one embodiment, it corresponds to a movable element that is accessible to the receiving unit. In some embodiments, the movable element is permanently attached to the housing, in particular embodiments, the movable element is connected to the housing, for example by a hinge. In other embodiments, the movable element may be detachable from the housing.

In some embodiments, the housing of the inhalation device has a fixed portion and at least one movable portion, the fixed portion comprising the pumping unit, the nozzle and the receiving unit, and the movable portion being movable from a closed state to an open state and/or from a rest position to an activated position.

The inhalation device, or more specifically the housing of the present inhalation device, comprises a receiving unit adapted to receive a replaceable reservoir or cartridge system as described in further detail below. The receiving unit has a connection unit adapted to be releasably fluidly connected to a connection port of the exchangeable reservoir. The term "fluid connection" as used herein means that, in terms of two elements, a connection, preferably a gas-and/or liquid-tight connection, is established or may be established that allows a fluid, such as a gas or a liquid, to be transferred from one element to another, preferably in such a way that the fluid is completely transferred from one element to the other.

In some embodiments, the movable portion of the housing is in the form of a cover that covers and encloses the receiving unit of the housing.

The receiving unit of the housing is adapted to receive, or in some embodiments, fully receive and fluidly connect to, a replaceable reservoir as described in further detail below. This means that, in particular with regard to the term "fully received" as used herein, such a replaceable reservoir may be fully introduced into the receiving unit of the housing, such that the receiving unit and the housing may fully enclose or encase the replaceable reservoir, preferably in such a way that: when introduced into the receiving unit, the surface of the exchangeable reservoir is completely surrounded by the housing of the inhalation device.

The inhalation device of the system of the present invention further comprises a nozzle for atomizing the medically active liquid. Those skilled in the art are aware of different kinds of nozzles suitable for nebulization, aerosol or aerosolization of a medically active liquid to be administered by the system of the present invention, such as impact nozzles, swirl nozzles, orifice nozzles, surface impact nozzles or multi-fluid nozzles. However, in certain embodiments, the nozzle of the present inhalation device is of the impact type. This means that the nozzle is adapted to discharge at least two liquid jets which are directed to impinge and break up into small aerosol droplets. In a particular embodiment, the nozzle is firmly attached to the housing, in particular to the user facing side of the housing of the inhalation device, such that the nozzle is fixed or immovable with respect to the housing or at least with respect to the user facing side of the housing (e.g. the patient), or more particularly the side or part of the nozzle that is introduced into the user's mouth when the device is used.

The inhalation device of the system of the present invention further comprises a pumping unit arranged within the housing of the inhalation device. The pumping unit is adapted to be fluidly connected to the reservoir, in particular via the connection unit of the receiving unit. In a particular embodiment, the pumping unit is fluidly connected to the reservoir via a connection unit of the receiving unit. Furthermore, the pumping unit is also adapted to be fluidly connected to the nozzle, or in a specific embodiment, to the nozzle, and is also adapted to deliver the medically active liquid from the reservoir to the nozzle, or in other words, to the nozzle, in a downstream direction.

In a particular embodiment, the inhalation device of the present invention comprises a pumping unit adapted and adapted to deliver the nebulized medically active liquid in a discontinuous manner, i.e. in the form of discrete units, wherein one unit is delivered per pumping cycle. In this regard, inhalation devices differ from commonly known nebulizers such as jet nebulizers, ultrasonic nebulizers, vibrating mesh nebulizers, or electrohydrodynamic nebulizers, which typically continuously generate and deliver a nebulized aerosol over a period of several seconds to several minutes, such that the aerosol requires multiple sequential respiratory events to be inhaled by a patient or user. In contrast, the inhalation device of the present invention is adapted to generate and expel discrete units of aerosol, wherein each unit corresponds to the amount (i.e. volume) of fluid (i.e. a medically active liquid) pumped by the pumping unit into the nozzle in one pumping cycle, wherein the fluid is immediately aerosolized and delivered to the user or patient. Vice versa, the amount of liquid pumped by the pumping unit in one pumping cycle determines the amount of pharmacologically active agent received by the patient per administration. Thus, it is very important that the pumping unit operates accurately, reliably and reproducibly for achieving the desired therapeutic effect. Such inhalation devices, which in particular comprise a pumping unit as described in further detail below, exhibit high precision and repeatability, are known to the person skilled in the art and are described in WO 2018/197730 A1, the disclosure of WO 2018/197730 A1 being incorporated herein in its entirety. However, it should be noted that the specific design of the pumping unit may vary, and that other pumping units, such as the unit described in US2012/0090603 Al, may also be used in the inhalation device of the present invention, US2012/0090603 Al being incorporated herein in its entirety by reference.

In a particular embodiment, the pumping unit may also be arranged within the housing and may be adapted to act as a piston pump, also called a plunger pump, wherein the standpipe acts as a piston or plunger and is longitudinally movable within the hollow cylinder. The pumping unit may have an upstream end fluidly connected to the replaceable reservoir and a downstream end fluidly connected to the nozzle. In a further particular embodiment, the pumping unit may comprise a riser, a hollow cylinder and lockable means for storing potential energy, the riser may be adapted to act as a piston in the pumping unit. The lockable device, such as a coil spring or other elastic element, is capable of storing potential energy when locked and may be adapted to release the stored energy when unlocked. The lockable device may be arranged outside the hollow cylinder and mechanically engaged to the hollow cylinder such that unlocking the device results in a pushing longitudinal movement of the cylinder towards the downstream end of the pumping unit. The inner section of such hollow cylinder forms a pumping chamber of variable volume depending on the position of the standpipe relative to the cylinder, the upstream end of such standpipe moving in the hollow cylinder.

Typically, if the lockable device for storing potential energy is locked and stores potential energy, the inhalation device system is in an activated state; in the activated state, the reservoir is in an activated position. If the lockable device for storing potential energy is released and unlocked, the inhalation device system is in a resting state and the replaceable reservoir is in a resting position.

The hollow cylinder providing the pumping chamber may be directly or indirectly (such as through an optional reservoir tube (or reservoir tube segment)) fluidly connected to the replaceable reservoir, or more specifically, directly or indirectly to a connection port of the replaceable reservoir. Similarly, the inner (upstream) end of the standpipe facing the reservoir may be received in a hollow cylinder, and the standpipe may be fluidly connected directly or indirectly to the nozzle in a fluid-tight manner at its downstream or outer end.

In this context, the expression "hollow cylinder" refers to a part or member that is hollow in the sense of comprising an internal void having a cylindrical shape, or comprising a segment having a cylindrical space. In other words, the external shape of the respective parts or members is not required to be cylindrical, as it is applicable to other types of piston pumps. Furthermore, the expression "hollow cylinder" does not exclude the following operating states of the respective parts or components: wherein the "hollow" space may be filled with a material, such as a liquid to be atomized.

As used herein, longitudinal movement is movement along the main axis of the hollow cylinder, while propulsive movement is movement of the component in a downstream (or forward) direction.

In a particular embodiment, the stand pipe of the pumping unit of the inhalation device of the present invention may be arranged downstream of the cylinder and may be firmly attached to the user facing side of the housing so as to be fixed with respect to the housing or at least with respect to the portion of the housing comprising the user facing side of the housing. For the avoidance of doubt, the term "fixedly attached" refers to attachment, either directly or indirectly (i.e. via one or more connecting members), to prevent relative movement between the various members. Since the nozzle is preferably also fixed relative to the housing or a corresponding part of the housing, the standpipe is preferably also fixed relative to the nozzle, and in these embodiments the pumping action is effected by longitudinal movement of the hollow cylinder. In this embodiment, the pushing movement of the cylinder arranged in an upstream position with respect to the standpipe results in a reduction of the volume of the pumping chamber, and the repelling movement of the cylinder results in an increase of the volume. In other words, in these embodiments, the standpipe maintains its position relative to the housing, and the hollow cylinder can change its position relative to the housing, particularly along the longitudinal axis of the housing, thereby effecting in-cylinder piston movement of the fixed standpipe in the movable cylindrical member.

This arrangement differs from other impact type suction devices, as disclosed in US2012/0090603 Al, which rely on a pumping unit with a standpipe in an upstream position and a cylindrical member in a downstream position, wherein the standpipe is movable and the cylindrical member is fixed to the housing. A key advantage of having a device for securing a riser as described above is that the channel between the pumping chamber and the exchangeable reservoir can be designed in such a way that it has less restrictions in terms of its dimensions. Because the inlet valve does not have to be accommodated in a narrow riser, a significantly larger and easier to manufacture inlet valve (also referred to as a check valve) can be accommodated. In contrast, the fixed riser design of the pumping unit allows the use of the following check valves: the size of which is limited only by the internal dimensions of the housing or the dimensions of the means for storing potential energy. In other words, the diameters of the valve, the standpipe and (if used) the reservoir tube need not match each other. Furthermore, since in this embodiment there is no need to connect the movable piston to the exchangeable reservoir, the means providing the fluid connection with the reservoir may be designed independently of the movable means (i.e. the hollow cylinder), allowing the individual parts to be adapted to their respective individual functions. In this regard, the fixed riser design according to this particular embodiment provides for a higher design flexibility because the movable hollow cylinder provides a better opportunity to design a mechanically stable connection with the reservoir due to its sturdy structure and size than a less sturdy movable riser. Furthermore, in this embodiment, the connection between the hollow cylinder and the exchangeable reservoir may be designed with a larger diameter, so that a higher flow rate and fluid viscosity becomes possible. Furthermore, the support for the exchangeable reservoir may be integrated into any component comprising the cylinder. Furthermore, in this embodiment, any vent for pressure balancing of the exchangeable reservoir may be transferred from the reservoir body itself to, for example, a connector forming an interface between the exchangeable reservoir and the hollow cylinder of the pumping unit, thereby facilitating construction and avoiding the necessity of providing a substantially "open" reservoir body. This is particularly important in the case of a reservoir designed as a replaceable reservoir, as is the case in the present invention.

As mentioned above, the lockable device for storing potential energy may be adapted to store energy in its locked state and to release the stored energy when unlocked. In a particular embodiment, the lockable device is mechanically engaged to the hollow cylinder such that unlocking the device results in a pushing longitudinal movement of the hollow cylinder towards the downstream end of the pumping unit. During this movement, the internal volume of the cylinder, i.e. the volume of the pumping chamber, decreases. Vice versa, when the means for storing potential energy are in the locked state, the hollow cylinder is in its most upstream position, in which the volume of the pumping chamber is maximum. The locked state may also be considered an activated state. When the state of the device for storing energy is changed from the unlocked state to the locked state (which may be referred to as activating the device), the hollow cylinder performs a repulsive longitudinal movement, i.e. a movement from its most downstream position towards its most upstream position. The pumping cycle comprises two successive opposite movements of the hollow cylinder: starting from its most downstream position to its most upstream (or start-up) position; and is driven back to its most downstream position by the lockable device for storing potential energy now releasing its energy. In a preferred embodiment, the exchangeable reservoir moves with the hollow cylinder during said movement.

In a particular embodiment, the pumping unit is a high pressure pumping unit and is adapted to operate or discharge fluid at a pressure of at least about 50 bar. In other preferred embodiments, the operating pressure of the pumping unit is at least about 10 bar, or at least about 100 bar, or about 2 bar to about 1000 bar, or about 50 bar to about 250 bar, respectively. As used herein, the operating pressure is the pressure at which the pumping unit discharges from its pumping chamber in the downstream direction (i.e. towards the nozzle) a pharmaceutically active liquid to be administered (such as an inhalable aqueous liquid formulation of a pharmacologically active ingredient). In this context, the expression "suitable for operation" means that the components of the pumping unit are selected in terms of material, size, surface quality and finish so as to be able to operate under a specific pressure.

Furthermore, such a high-pressure pumping unit means that the lockable device for storing potential energy is capable of storing and releasing a sufficient amount of energy to drive the propelling longitudinal movement of the cylinder with a force to obtain a corresponding pressure.

The lockable device for storing potential energy can be designed as a tension spring or a compression spring. Alternatively, in addition to a metal body or a plastic body, a gaseous medium or a material using magnetic force may be used as a means for energy storage. By compression or tensioning, potential energy is fed to the device. One end of the device may be supported at or within the housing at a suitable location; thus, this end is substantially fixed. The other end of the device may be connected to a hollow cylinder of a pumping unit providing a pumping chamber; thus, this end is essentially movable. The means for storing potential energy may be locked after a sufficient amount of energy is carried so that energy may be stored until unlocking occurs. When unlocked, the device may release potential energy (e.g., spring energy) to a cylinder having a pumping chamber, which is then driven for movement (in this case, longitudinally). Typically, the energy release occurs suddenly, so that a high pressure can be built up in the pumping chamber before a large amount of the medically active liquid is discharged, which can lead to a pressure drop. In fact, during a significant part of the discharge phase, there is a balance between the pressure transmitted by the means for storing potential energy and the amount of medically active liquid that has been discharged. Thus, during this phase the amount of the medically active liquid remains substantially constant, which is a significant advantage for devices that utilize manual force of the user for draining, such as the devices disclosed in documents US2005/0039738 Al, US2009/0216183 Al, US2004/0068222Al or US2012/0298694 Al, since the manual force is dependent on the individual user or patient and is likely to vary greatly during the draining phase, resulting in uneven droplet formation, size and number. The device according to the invention ensures that the inhalation device provides highly reproducible results compared to the prior art.

In a further embodiment, the means for storing potential energy may also be provided in the form of a high pressure gas container. With the proper arrangement and repeatable intermittent activation (i.e., opening) of the arrangement, a portion of the energy stored within the gas container may be released to the gas cylinder. This process may be repeated until the remaining energy is insufficient to again build up the desired pressure in the pumping chamber. After this, the gas container must be refilled or replaced.

In a particular embodiment, the lockable device for storing potential energy is a spring having a load of at least 10N in the deflected state. In a preferred embodiment, the means for storing potential energy is a compression spring made of steel having a load of about 1N to about 500N in its deflected state. In other preferred embodiments, the steel compression spring has a load of about 2N to about 200N, or about 10N to about 100N, in its deflected state.

In a preferred embodiment, a single dose of the drug (i.e. an aerosol of the nebulized medically active liquid) is contained in one unit, i.e. in the volume delivered from the pumping unit to the nozzle, for generating the aerosol in one single pumping cycle. In this case, the user or patient will only need to activate and actuate the device once per administration (i.e. per administration event) and inhale the released aerosol in one breath action.

In another preferred embodiment, a single dose of drug consists of two units of aerosol, thus requiring two pumping cycles. Typically, the user or patient will activate the inhalation device, actuate it to release and inhale a unit of aerosol, and then repeat the process. Alternatively, three or more aerosol units may constitute a single dose.

The volume of fluid (e.g., a medically active liquid) pumped by the pumping unit of the present inhalation device system in one pumping cycle may preferably be in the range of about 0.1 μl to about 1000 μl, or in the range of about 1 μl to about 250 μl, or in the range of about 2 μl to about 150 μl. In particular, the volume may be in the range of about 2 μl to about 50 μl, or in the range of about 5 μl to about 25 μl, more particularly in the range of about 10 μl to about 20 μl, such as about 15 μl. These volume ranges are almost the same as the volume of liquid phase contained in one unit of aerosol produced by the inhalation device, but may have minor differences due to minor losses of liquid in the device.

In a further particular embodiment, the pumping unit of the inhalation device comprises an inlet valve, also called a check valve or inlet check valve, positioned in the hollow cylinder. According to this embodiment, the inner space of the hollow cylinder, i.e. the pumping chamber, is fluidly connected with the fluid reservoir via an inlet check valve. While the inlet valve allows liquid to flow into the pumping chamber, the medically active liquid is prevented from flowing back towards or back into the replaceable fluid reservoir. In a preferred embodiment, the inlet valve may be located at or near the upstream end of the cylinder so that substantially the entire internal volume of the hollow cylinder may be used to act as a pumping chamber. Alternatively, the inlet valve may be more centrally located along the (longitudinal) main axis of the hollow cylinder to define an upstream section of the cylinder upstream of the inlet valve and a downstream section downstream of the inlet valve. In this case, the pumping chamber is located in the downstream section.

As mentioned above, one of the advantageous effects of a particular embodiment of the pumping unit with a fixed or non-movable piston as described above is that an inlet valve with a relatively large size can be accommodated at this location, i.e. at the upstream end of the pumping chamber. This is particularly advantageous because it allows the fluid conduit within the valve to have a larger size, thereby achieving a high fluid velocity which translates into a rapid filling of the pumping chamber during actuation of the inhalation device. Furthermore, for inhalation therapy, it is also possible to use a medical active liquid having a higher viscosity than that of a general liquid preparation for inhalation (such as a high concentration solution of a soluble active ingredient).

In a further embodiment, the inlet valve may be adapted to open only when the pressure difference between the upstream side and the downstream side of the valve (i.e. the fluid reservoir side and the pumping chamber side) is above a predetermined threshold value, and to remain closed as long as the pressure difference is below this threshold value. In this context, the term "pressure difference" means that, regardless of the absolute pressure value, only the relative pressure difference between the two sides is relevant to determining whether the valve is closed or open. For example, if the pressure on the upstream (reservoir) side is already positive (e.g. due to thermal expansion, 1.01 bar), but the pressure on the downstream (pumping chamber) side is ambient pressure (e.g. 1.0 bar, no activation means), the pressure difference (here: 0.01 bar) is below a threshold value (e.g. 20 mbar), which causes the valve to remain closed even if subjected to positive pressure in the opening direction. This means that the check valve remains closed until the threshold pressure is reached, thus keeping the passage between the reservoir and the pumping chamber safely closed, for example when the inhalation device is not in use. Examples of threshold pressure differences are between 1 and 1000 millibar, more preferably between about 10 and about 500 millibar, or between about 1 and about 20 millibar.

When the inhalation device of the present inhalation device system is actuated, energy is released as the means for storing potential energy changes its state from a locked state to an unlocked state, causing the air cylinder to perform a propelling longitudinal movement and creating a significant pressure in the pumping chamber. A significant pressure differential is created due to the high pressure in the pumping chamber and the significantly lower pressure in the fluid reservoir, which exceeds the threshold value of the pressure differential, so that the check valve opens and allows the pumping chamber to fill with medical liquid from the replaceable reservoir.

The type of valve that may be designed to operate with such a threshold pressure differential is a preloaded spring ball valve. The spring pushes the ball into the valve seat and the ball valve will open only when the pressure acting against the spring force exceeds the spring force. Other valve types that may be operated with such a threshold pressure differential depending on the configuration are duckbill valves or flap valves.

An advantage of such a valve operated with a threshold pressure difference is that the reservoir may remain closed until the inhalation device is actively used, thereby reducing unwanted splashing of the medically active liquid stored in the cartridge system during transport of the device, or evaporation during long-term storage of the device.

In a further particular embodiment, the suction means of the system according to the invention may further comprise an outlet valve inside the riser or at the end of the riser, to avoid backflow of liquid or air from the riser into the hollow cylinder. In many cases, the use of such outlet valves has proven to be advantageous. Typically, the downstream end of the standpipe is located near the nozzle. The nozzle is in fluid communication with the outside air. The pumping chamber must be refilled, driven by the advancing longitudinal movement of the cylinder, after a certain amount of the medically active liquid delivered from the pumping unit is expelled in aerosol form through the nozzle. For this purpose, the cylinder slides back on the standpipe to its previous upstream position (i.e. performs a repulsive longitudinal movement), thereby increasing the internal volume of the pumping chamber. At the same time, a relatively negative pressure (sometimes also referred to as "negative pressure") is created within the pumping chamber, which causes liquid to be drawn into the pumping chamber from a replaceable reservoir located upstream of the pumping chamber. However, this relative negative pressure may also propagate downstream through the standpipe to the outside of the nozzle and may cause air to be drawn into the device through the nozzle or nozzle opening, respectively. This problem can be avoided by providing an outlet valve (also called outlet check valve) which is open towards the nozzle opening and which blocks in the opposite direction.

Alternatively, as described in the context of the inlet valve described above, the outlet valve is of a type that blocks below a threshold pressure differential (and opens above the threshold pressure differential). If a ball valve with a spring is used, the spring force must be directed to the pumping chamber such that the outlet valve opens when the difference between the internal pressure of the pumping chamber and the ambient pressure exceeds a threshold pressure difference. The advantages of such a valve correspond to the respective advantages described above.

As described above, the outlet valve may be positioned within the riser as described above. Alternatively, the inhalation device comprises an outlet valve which is not integrated within the standpipe, but is positioned at or near one end of the standpipe, in particular at or near its downstream end (e.g. in a separate connector between the standpipe and the nozzle). This embodiment may be advantageous in certain situations, for example, where a particularly small diameter riser is required, thereby making integration of the valve difficult. By accommodating the outlet valve downstream of the standpipe, a relatively large diameter valve can be used, simplifying the requirements on valve design.

In a further alternative embodiment, no outlet valve is present. This embodiment may be possible because the fluid channel of the impulse nozzle may have a relatively small cross-section, resulting in only a small or very slow back flow of the medically active liquid under given pressure conditions during actuation of the inhalation device. If the amount of reflux is considered acceptable in view of the particular product application, the design of the inhaler can be simplified by omitting the outlet valve.

In any case, all other options and preferences described for other device features apply to both alternative embodiments, whether the inhalation device is designed with or without an outlet valve.

The inhalation device system of the present invention comprises a replaceable reservoir for containing a medically active liquid provided in the form of a cartridge system. The cartridge system of the present invention has a total volume V ₀ Wherein the term "total volume" as used herein refers to the volume of the entire cartridge system, including all parts thereof, such as the outer wall of the cartridge system. In a typical embodiment, the total volume V of the entire cartridge system ₀ May be selected in the range of about 0.1mL to about 100mL, or in the range of about 0.1mL to about 50mL, or in the range of about 0.2mL to about 30mL, such as in the range of about 2.5mL to about 20mL, or in the range of about 5mL to about 15 mL.

The replaceable cartridge system of the present invention has an upstream end and a downstream end and includes a container portion having an effective volume V for containing a medically active liquid and a connection port _e The connection port is adapted to releasably fluidly connect the cartridge system to the pumping unit, in particular via a connection unit of a receiving unit of the inhalation device.

In an exemplary embodiment, the effective volume V of the container portion of the present replaceable cartridge system _e Selected in the range of about 0.1mL to about 50mL, or in the range of about 0.1mL to about 25mL, or in the range of about 1mL to about 15mL, or in the range of about 1mL to about 10mL, specifically in the range of about 3mL to about 6mL, or in the range of about 6mL to about 9mL, more specifically in the range of about 4.0mL to about 5.0mL, or in the range of about 7.0mL to about 8.0 mL.

In certain embodiments, the connection port of the container portion may be in the form of a cap, such as a cap mounted on the downstream end of the container portion. The connection port may have an opening that allows for establishing a fluid connection with the interior cavity of the container portion and the medically active liquid contained therein. The term "effective volume" refers to the volume of the entire container portion, including all components thereof, such as the outer wall of the container portion or a connection port (such as a cap). The term "cavity" or "lumen" as used herein in connection with a hollow body such as a container portion or other component refers to an interior space or cavity within such hollow body, whether or not such interior space or cavity is completely or only partially surrounded by an outer wall of the hollow body.

In a further specific embodiment, the container portion of the present replaceable cartridge system may be in the form of a flexible container, or may be in the form of a rigid container (or in other words, a dimensionally stable container). The term "rigid" or "dimensionally stable" as used herein refers to the container portion not changing its shape or volume when the medically active liquid contained therein is expelled from the container during standard operation of the present inhalation device system, or in other words, when the medically active liquid is withdrawn from the container portion by the pumping unit during nebulization and administration of the medically active liquid. In a particular embodiment of the inhalation device system, the container portion of the replaceable cartridge system is in the form of a dimensionally stable container. In a further specific embodiment, the container portion of the present replaceable cartridge system is in the form of a dimensionally stable container comprising a flexible or collapsible inner container as described in further detail below, wherein the inner container contains a medically active liquid to be administered by the inhalation device system of the present invention.

In general, the container portion, particularly when provided in a dimensionally stable form, may have any suitable shape that allows for the introduction of the container portion or the entire replaceable cartridge system comprising such container portion into an inhalation device of the present inhalation device system. In particular embodiments, suitable shapes include, but are not limited to, bottle-like or tubular or cylindrical, where symmetrical and asymmetrical shapes may be achieved. This may achieve an advantageous embodiment, in particular with respect to the axial symmetry of the container device or the entire cartridge system about a main rotational axis connecting the centre of its upstream end with the centre of its downstream end, in which embodiment the container device or the cartridge system may be inserted into the inhalation device in a specific orientation only or may not be inserted into the inhalation device in a specific orientation only. However, in a preferred embodiment, the inhalation device or the entire cartridge system may have a substantially circular cross-sectional shape such that the container device or the cartridge system may be introduced into the inhalation device independently of the rotational orientation about the longitudinal spindle.

In a further embodiment, the container portion may be in the form of a bottle having a (main) opening, preferably at the downstream end of the bottle, for filling or draining the medically active liquid to be stored and administered. It should be noted, however, that the container portion may comprise further (secondary) openings, for example for ventilation purposes.

In a specific implementationIn an embodiment, the container portion of the replaceable reservoir may include an inner container containing a medically active liquid and having a maximum internal volume V _i . The term "internal volume" (V) as used herein in relation to the container portion _i ) Refers to the total internal volume of the container portion that may be (partially or completely) filled with a liquid, in particular a medically active liquid to be administered by the inhalation device system according to the present invention. Thus, the internal volume V of the container part completely filled with the medically active liquid _i Corresponds to the volume of the medically active liquid contained in such a fully filled container portion. In a typical embodiment, the maximum internal volume V _i Substantially corresponding to the effective volume V of the container portion _e And may preferably be selected in the range of 0.1mL to about 15mL, or in the range of about 1mL to about 10mL, specifically in the range of about 3mL to about 6mL, or in the range of about 6mL to about 9mL, more specifically in the range of about 4.0mL to about 5.0mL, or in the range of about 7.0mL to about 8.0 mL. However, in a further embodiment, the maximum internal volume V of the inner container is selected _i Can be smaller than the effective volume V of the container part _e This results in the case that not the entire cavity of the container portion is filled with an optional inner container.

For example, the inner container, which may be accommodated in the container portion of the reservoir, may be designed to be collapsible, such as by a flexible or elastic wall. The effect of this design is that upon repeated use of the device involving progressive emptying of the reservoir, the flexible or elastic wall bends or folds to reduce the internal volume of the reservoir, so that the negative pressure required to extract a certain amount of liquid during use does not need to be significantly increased. In particular, the alternative inner container of the exchangeable holder may be designed as a collapsible bag. The advantage of a collapsible bag is that the pressure inside the reservoir is almost independent of the filling level and that the effect of thermal expansion is almost negligible. Furthermore, the construction of this type of reservoir is rather simple and already mature. However, in further embodiments, the inner container may have a non-flexible or rigid form, wherein pressure equalization with the surrounding atmosphere during administration of the medical liquid stored therein is achieved by other means, such as an inlet valve or a movable piston.

In certain embodiments, the container portion of the cartridge system may be made or fabricated from a polymeric material, in particular a thermoplastic polymer such as polyethylene, polypropylene, polyoxymethylene (POM), and polystyrene. In alternative embodiments, the container portion may be made of a metal such as stainless steel, aluminum, or other suitable metals or mixtures thereof. However, in a preferred embodiment, the container portion is made of polyethylene or polypropylene, preferably polypropylene. It should be noted, however, that the separate structure of the container part, such as the connection port, which is preferably in the form of a lid, may be formed of the same or another metallic or non-metallic material as described above.

In general, the cartridge system may have a symmetrical or asymmetrical cross-sectional shape. An asymmetric cross section may be advantageous in case it is important for the cartridge system to be introduced or received in the receiving unit of the inhalation device only in a specific orientation. On the other hand, in particular for facilitating insertion of the cartridge system, it may be advantageous for example for infants or disabled users to have a symmetrical cross-section, such as a circular cross-section (perpendicular to the main central axis connecting the downstream and upstream ends of the exchangeable cartridge system).

The inhalation device system of the present invention comprises a combined counting and blocking assembly comprising a counting unit for counting the number of actuations of the inhalation device system and a blocking unit for blocking the movement of the exchangeable reservoir from the rest position to the activated position when a defined number of actuations is reached. The counter unit and the blocking unit are physically separated from each other when the exchangeable reservoir is in the rest position, and the counter unit and the blocking unit are adapted to interact with each other each time the exchangeable reservoir is moved from the rest position to the activated position.

In a preferred embodiment, the counting and blocking assembly is manually operated and does not include electronic components.

The blocking unit of the assembly prevents further use of the reservoir after a predetermined number of uses. The inhalation device system may comprise a further blocking mechanism which prevents use of the inhalation device system under defined conditions. Examples of such a blocking system are found in WO 2019/122251 A1. If additional blocking systems are included in the inhalation device system, the blocking systems may work in conjunction with each other or independently of each other.

The counting and blocking assembly of the invention is characterized in that the blocking unit and the counting unit are physically separated from each other when the exchangeable reservoir is in the rest position. Thus, the two units may be reset and/or replaced independently of each other.

In the context of the present invention, physically separated from each other means that the movable part of the counting assembly is not in contact with the movable part of the blocking assembly when the reservoir is in the rest position. In some embodiments, the counter unit and the blocking unit may each independently include a housing that separates the components of the two. The housings of the individual units may or may not be permanently in contact and include openings that allow the blocking unit and the movable portion of the counting unit to interact when the reservoir is moved.

In a preferred embodiment, the blocking unit and the counting unit each comprise a housing separating the two systems. Preferably, the two housings are not in contact with each other when the exchangeable reservoir is in the rest position, and the two housings are in contact or at least very close to each other when the exchangeable reservoir is in the activated position.

The counting assembly and the blocking assembly interact when the inhalation device is ready to be used and the reservoir is moved to the activated position. In the context of the present invention, interaction means bringing at least two units into close physical proximity. In a preferred embodiment of the invention, the counting unit and the blocking unit of the combined counting and blocking assembly interact with each other when the reservoir is moved.

The interaction may be bi-directional or unidirectional. Preferably, the type of interaction depends on the state of the inhalation device system. For example, in one embodiment, the blocking unit and the counting unit may be bi-directional when the replaceable reservoir is replaced and not in use, the blocking unit resetting the counting unit and the counting unit activating the blocking unit. If the predetermined number of uses of the reservoir is reached, the interaction will cause the blocking mechanism of the blocking unit to activate and block further uses of the reservoir. The blocking unit may activate the counting unit if the reservoir is in use and has not reached a predetermined number of uses.

The result of said interaction between the blocking unit and the counting unit preferably depends on the state of the inhalation device and the exchangeable reservoir. For example, if a new reservoir is inserted, the interaction between the counting unit and the blocking unit may reset the counting unit and/or initialize the blocking unit. After a predetermined number of uses, the interaction between the counting unit and the blocking unit activates the blocking unit and blocks further use of the reservoir. Between these two states, the interaction may be limited and may include only bringing the two units into contact, i.e. bringing the movable part of one unit into contact with the movable part of the other unit, or the interaction is limited to moving the part of one unit through the other unit into the opening of the housing of the one unit. In some embodiments, the counting unit may be reset, preferably after replacement of the reservoir or by replacement of the reservoir. Preferably, the counting unit comprises an indexing means (indexing means) to indicate the number of actuations and/or remaining uses of the inhalation device system before the reservoir is replaced.

In a particular embodiment, the blocking unit resets or activates the counting unit upon interaction after insertion of a new exchangeable reservoir and after the counting unit activates the blocking mechanism in the blocking unit. When the device is used after insertion of the exchangeable reservoir, but the maximum number of uses of the reservoir has not been reached, the blocking unit activates the counting unit to count the number of uses during each interaction. Once the predetermined number of uses is reached, the counting unit activates the blocking unit and prevents further use of the reservoir.

In some embodiments, the interaction between the units is achieved by movement of one unit. In a preferred embodiment, the blocking unit may be moved or axially or longitudinally moved during the activation step of the device, so as to interact with the counting unit while the latter remains in the same axial position. In some embodiments, the counting unit may be moved or moved axially or longitudinally during the activation step of the device, so as to interact with the blocking unit.

The counting unit and the blocking unit may be firmly attached to the inhalation device system or a component thereof. The counting unit and the blocking unit may be attached or connected to different parts of the inhalation device system. In some embodiments, one unit is attached to the housing and the other unit is attached to the replaceable reservoir. In some embodiments, one unit is reversibly and replaceably attached to the housing, while the other unit is fixed to the replaceable reservoir. In some embodiments, one unit is permanently attached to the housing or a portion thereof, while the other unit is permanently attached to the replaceable reservoir and replaced with the reservoir.

In some embodiments, the counting unit is attached to a housing of the inhalation device system. In a particular embodiment, the counting unit is attached to the lower part of the housing. In some embodiments, the housing lower portion is removable or detachable. In some embodiments, the counting unit is removably connected to the housing lower portion. In another embodiment, the counting unit is non-removably connected to the lower part of the housing. The lower housing portion may be removable or detachable to allow replacement of the replaceable reservoir.

In some embodiments, the counting unit is attached to an inner surface of a housing of the inhalation device system. In a particular embodiment, the counting unit is removably attached to the inner surface of the housing. In other embodiments, the counting unit is permanently attached to the inner surface of the housing. In some embodiments, the counting unit is attached to an inner surface of the movable portion of the housing.

In some embodiments, one unit of the counting and blocking assembly is attached to the replaceable reservoir. In a preferred embodiment, the blocking unit of the modular assembly is attached to the exchangeable reservoir. In some embodiments, the blocking unit is securely attached to the replaceable reservoir and replaced with the reservoir. In these embodiments, the blocking unit moves with the reservoir in the inhalation device system. In order to allow smooth operation of the inhalation device system, it is preferred that the entire cartridge assembly does not interfere with the inhaler body. Thus, preferably, the blocking unit has substantially the same cross-sectional diameter as the exchangeable reservoir. In some embodiments, the cross-sectional diameter is smaller than a cross-sectional diameter of the reservoir. It is particularly preferred that the blocking unit and the exchangeable reservoir have a circular cross section.

The blocking unit may be attached to the exchangeable reservoir in any way. The person skilled in the art knows suitable means for attachment. The blocking unit may be glued or welded to the exchangeable reservoir. Preferably, the blocking unit is attached to an outer surface of the exchangeable reservoir. In some embodiments, the blocking unit is attached to the outer surface of the replaceable reservoir by a force fit connection or a form fit connection.

The blocking unit may be attached to the exchangeable reservoir by a housing of the blocking unit. The housing of the blocking unit may comprise an opening at the downstream end, which opening is connected to the exchangeable reservoir. The opening of the housing of the blocking unit desirably has a diameter corresponding to the outer diameter of the upstream end of the replaceable reservoir. The opening may for example comprise a thread for connecting the blocking unit to the exchangeable reservoir.

The replaceable reservoir may be in the form of a replaceable cartridge having an upstream end and a downstream end, and the blocking unit is attached to the upstream end of the replaceable reservoir.

If the barrier unit is attached to the exchangeable reservoir, the barrier unit and the exchangeable reservoir are preferably assembled and sterilized before filling the reservoir with the medically active liquid.

Preferably, the blocking unit is not removable or is difficult to remove from the reservoir. In a preferred embodiment, wherein the blocking unit is attached to the exchangeable reservoir, the force required to remove the blocking unit from the exchangeable reservoir is greater than the force required to remove the exchangeable reservoir from the receiving unit of the inhalation device. In these embodiments, the blocking unit is replaced with the reservoir.

In some embodiments, the exchangeable reservoir is provided in the form of a cartridge having an outer (dimensionally stable) housing comprising an inner container in the form of a bag, in particular in the form of a collapsible bag, containing the medically active liquid, and to which the blocking unit is attached.

In some embodiments, the replaceable reservoir comprising the blocking unit has a cylindrical shape with a central longitudinal axis (a) connecting a connection port (32) of the replaceable reservoir (31) at a downstream end of the replaceable reservoir (30) with an upstream end of the blocking unit attached to the upstream end of the replaceable reservoir.

The blocking unit includes a blocking mechanism.

In some embodiments, the blocking unit further comprises a housing comprising the blocking mechanism. In a preferred embodiment, the blocking unit comprises a housing and a blocking mechanism, wherein the housing of the blocking unit comprises an opening for interaction between the counting unit and the blocking mechanism. In some embodiments, the opening is located at an upstream end of the blocking unit.

The blocking mechanism preferably prevents the exchangeable reservoir from moving from the rest position to the activated position after activation.

This movement may be prevented by the blocking unit itself or by interaction with other parts of the inhalation device system. In a preferred embodiment, the blocking mechanism blocks movement of the exchangeable reservoir together with the activation mechanism of the counting unit.

The counting unit comprises a counting mechanism and an activating mechanism. The counting mechanism counts actuation of the inhalation device system. The term "actuation of the inhalation device system" refers to all steps that initiate the release of fluid. The steps include: rotating the lower portion of the housing to activate the mechanism to move the reservoir to the activated position; the actuator member is activated to release the reservoir from the activated position and release the fluid.

In the context of the present invention, the counting mechanism thus preferably counts at least one of the following:

rotation of at least one housing part;

movement of the exchangeable reservoir;

activation of the actuator member.

In a preferred embodiment, the counting mechanism counts the actuations as early as possible. For example, if the counting mechanism counts the rotations of the lower part of the housing, it is preferable to count the rotations earlier during the rotations. In a preferred embodiment, the counting mechanism is activated by a vertical movement of a counting member which is moved by rotating the lower part of the housing. The counting member may be part of the blocking unit.

The counting unit may comprise indicator means for displaying the number of uses. In some embodiments, the indicator device displays the remaining number of uses of the reservoir, while in other embodiments, the indicator device displays the number of uses of the reservoir.

Alternatively, it is also possible to choose: the counting mechanism is operated by the interaction of the blocking unit with the counting unit when the exchangeable reservoir is moved from the rest position to the activated position.

In addition to the counting mechanism, the counting unit also comprises an activation mechanism. In a preferred embodiment, the activation mechanism interacts with the blocking unit, preferably with a blocking mechanism of the blocking unit.

The result of the interaction of the activation mechanism with the blocking unit depends on the state of the blocking unit and the counting unit. In a preferred embodiment of the invention, the interaction of the activation mechanism with the blocking unit will result in one of the following:

if the reservoir is replaced after a predetermined number of uses, the interaction will reset the counting unit;

if the reservoir is already in use and a predetermined number of uses is reached, the interaction will activate the blocking mechanism and prevent further use of the reservoir;

If the reservoir is already in use, but the predetermined number of uses has not been reached, the interaction will not be active, or the interaction will activate the counting unit, counting one use of the inhalation device system.

In some embodiments, the activation mechanism includes an activation member. In a preferred embodiment, the activation mechanism comprises a movable activation member. The activation member may be a gear or a pin. In a preferred embodiment, the activation member is a pin. In some embodiments, the activation mechanism is driven by a counting mechanism. In other embodiments, the activation mechanism may be driven independently of the counting mechanism.

In some embodiments, the activation member of the activation mechanism interacts with the blocking mechanism and/or the counting mechanism. In some embodiments, the activation member interacts with a movable element in the blocking mechanism. In some embodiments, the activation member is a pin that interacts with the blocking mechanism after a predetermined number of uses. For example, after a predetermined number of uses of the reservoir, the activation member deflects the movable member in the blocking mechanism, resulting in activation of the blocking mechanism. In some embodiments, the activation of the blocking mechanism is reversible. In a preferred embodiment, said activation of the blocking mechanism is irreversible.

In a preferred embodiment, the activation member of the activation mechanism of the counter unit enters the opening of the blocking unit to interact with the blocking mechanism when the exchangeable reservoir is moved from the rest position to the activated position. Once a predetermined number of uses is reached, the movable activation member activates the blocking mechanism.

In some embodiments, the movable activation member is driven by a counting mechanism. In some embodiments, the movable activation member is moved gradually or stepwise with each activation of the counting mechanism. In this case, the activation member may be a pin protruding from the counter unit, which pin interacts with the blocking unit when the reservoir is moved. The pin may change position when the counting unit is activated. In this way, the position of the activation member is controlled by the counting unit.

In a preferred embodiment, the activation member is movable and gradually movable, for example by stepwise movement, and the position of the member is dependent on the number of uses of the exchangeable reservoir.

In a preferred embodiment, the activation member is controlled by a counting mechanism. In some embodiments, the counting mechanism includes a rotatable member having an optional circular inclined ramp upon which the activation member is supported. In a preferred embodiment, each activation of the counting mechanism causes the rotatable member to move on the inclined ramp, preferably by sliding on the upper surface of the inclined ramp.

In a preferred embodiment, the rotatable member is moved, preferably gradually, along the inclined surface of the ramp under the drive of the counting mechanism. Movement of the rotatable member also drives the activation member, which moves slowly upward in an axial or downstream direction as the rotatable member moves over the inclined surface. When the rotatable member reaches the highest point of the ramp, the activating member is in the highest position.

In a particular embodiment of the invention, the activation member is at the highest point of the inclined surface after said predetermined number of uses and/or at the highest point when a new exchangeable reservoir is inserted. Subsequent actuation of the inhalation device system will move the activation member to the lowest position on the inclined surface after replacement of the reservoir, preferably resetting the counting unit simultaneously. Each actuation of the inhalation device system will then cause the activation member to move gradually, for example by a stepwise movement, to move to the uppermost position on the tilting member, when the uppermost position is reached after a predetermined number of uses, the blocking mechanism of the blocking unit is activated.

The rotatable member and the activation member may be one single piece or may be two separate pieces. In a preferred embodiment, the rotatable member and the activation member are one piece or the activation member is connected to the rotatable member.

In a particular embodiment, the blocking mechanism includes an opening for the activation member. The opening allows access for the activation member, which will be limited by the blocking element after activation of the blocking mechanism. After a predetermined number of uses, the activation member will be positioned towards the upper end of the ramp and prevent greater movement of the reservoir due to the limited space behind the opening, since the blocking member is preferably no longer movable until the reservoir is replaced to allow resetting of the counting mechanism.

In a particular embodiment, the blocking system comprises two members connectable to each other. The member has a moving configuration and a blocking configuration. The first member or stationary member comprises a hollow tube in which at least a portion of the second member or moving member is movable. In the mobile configuration, the second member is driven by the activation member of the counting unit during movement of the reservoir and moves within the hollow tube of the first member. The members may be implemented as plungers and cams. In the mobile configuration, the non-mobile member maintains the same relative position with respect to the reservoir. If the activation member is moved far enough after a predetermined number of uses, the two members interlock in a blocking configuration. In the blocking configuration, the two members move to a blocking position, optionally interlocking, and restricting space for the activation member. In the blocking position, both members are stationary and cannot move.

In alternative embodiments, the blocking system may comprise two members, a moving member and a guiding member. The guide member includes a hollow tube that allows the moving member to move. The moving member and the guide member may be implemented in the form of a plunger and a cam. The movement of the moving element is driven by the activation member of the counting unit. The moving member or the guiding member may comprise a protruding element. The blocking unit optionally comprises a recess or a corresponding protrusion which fits the protruding element of one of the above mentioned components. Depending on the number of uses, the moving element moves during actuation of the inhalation device system. After a predetermined number of uses, the projection of the moving element or the guiding element moves into said recess, preventing further movement of the moving element, thereby restricting the space behind the opening to allow the activation member to only partially enter through the opening of the housing of the blocking unit and thus avoiding complete entry of the activation member.

In another aspect, the present invention relates to a method of containing a medically active liquid for nebulization andand is suitable for a cartridge system of an inhalation device system (10) as defined above. The replaceable cartridge system of the present invention has an upstream end and a downstream end and includes a container portion having an effective volume V for containing a medically active liquid and a connection port _e The connection port is adapted to releasably fluidly connect the cartridge system to the pumping unit, in particular via a connection unit of a receiving unit of an inhalation device, wherein a blocking unit as defined above is connected to an upstream end of the container portion.

The general cartridge system has been defined and explained in detail above and the above details may be combined with the specific embodiments defined below.

In a further particular embodiment, the container part of the present replaceable cartridge system is in the form of a dimensionally stable container to which the blocking unit as defined above is attached.

The blocking unit may be permanently or removably attached. Preferably, the blocking unit is permanently attached. The blocking unit is a blocking unit as defined above and preferably comprises a housing connected to the container. The housing may be of the same or different material as the container, the outer housing of the cartridge.

As mentioned above, the cartridge system is preferably assembled and sterilized prior to filling the cartridge system with the medical fluid.

In another aspect, the present invention relates to an inhalation device for an inhalation device system, wherein the inhalation device comprises:

-a housing having a receiving unit with a connection unit adapted to be releasably fluidly connected to a connection port of the exchangeable reservoir, the receiving unit being adapted to receive and be fluidly connected to the exchangeable reservoir;

-a nozzle for atomizing a medically active liquid; and

a pumping unit arranged within the housing, adapted to be fluidly connected to the nozzle and the exchangeable reservoir, adapted to deliver the medically active liquid from the exchangeable reservoir to the nozzle in a downstream direction, and adapted to move the exchangeable reservoir from a rest position to an activated position when the pumping unit is activated,

wherein the inhalation device comprises at least one of the following:

a counting unit as defined above, adapted to interact with the blocking unit; and/or

A blocking unit as defined above, adapted to interact with the counting unit.

In a preferred embodiment, the inhalation device comprises a counting unit as defined above adapted to interact with the blocking unit. In a particular embodiment, the blocking unit interacting with the counting unit is part of the exchangeable reservoir. The inhalation device may comprise other blocking means for blocking operation, but which do not interact with the counting unit in a manner as defined above.

The invention further relates to the following numbered examples:

1. an inhalation device system (10) for inhalation administration of a medically active liquid in an aerosolized form, the system comprising an inhalation device (20) and a replaceable reservoir (30) for containing a plurality of doses of the medically active liquid, wherein a dose of the medically active liquid is dispensed from the inhalation device each time the inhalation device system is actuated,

Wherein the inhalation device (20) comprises:

-a nozzle (25) for atomizing a medically active liquid; and

a pumping unit (40) arranged within the housing (21) adapted to be fluidly connected to the exchangeable reservoir (30) and the nozzle (25), adapted to transfer a medically active liquid from the exchangeable reservoir (30) to the nozzle (25) in a downstream direction, and adapted to move the exchangeable reservoir from a rest position to an activated position upon activation of the pumping unit,

Wherein the counting unit and the blocking unit are physically separated from each other when the replaceable cartridge is in the rest position, and the counting unit and the blocking unit are adapted to interact with each other each time the replaceable cartridge is moved from the rest position to the activated position.

2. The inhalation device system according to item 1, wherein the counting unit is attached to the housing of the inhalation device.

3. The inhalation device system according to item 1 or 2, wherein the blocking unit is attached to the replaceable reservoir.

4. An inhalation device system according to any preceding claim, wherein the combined blocking and counting unit is manually operated and does not comprise electronic components.

5. An inhalation device system according to any preceding claim, wherein the housing of the inhalation device has a fixed portion (comprising the pumping unit, the nozzle and the receiving unit) and a movable portion (movable from a closed to an open state and from a rest to an activated position), and wherein the counting unit is attached to the movable portion of the housing.

6. The inhalation device system according to item 5, wherein the movable portion of the housing is in the form of a cover which covers and closes the receiving unit of the housing.

7. An inhalation device system according to any preceding claim, wherein the counting unit is (permanently) attached to an inner surface (of the movable part) of the housing of the inhalation device.

8. An inhalation device system according to any preceding claim, wherein the counting unit (upon replacement of the replaceable reservoir) is resettable.

9. An inhalation device system according to any preceding claim, wherein the blocking unit is firmly attached to the exchangeable reservoir.

10. The inhalation device system of any one of claims 1 to 8, wherein the blocking unit is releasably attached to the replaceable reservoir.

11. An inhalation device system according to any preceding claim, wherein the replaceable reservoir is in the form of a replaceable cartridge having an upstream end and a downstream end, and the blocking unit is attached to the upstream end of the replaceable cartridge.

12. An inhalation device system according to any preceding claim, wherein the barrier unit has a housing containing the barrier mechanism.

13. The inhalation device system of claim 12, wherein the housing of the blocking unit comprises an opening for physical interaction between the counting unit and the blocking mechanism.

14. The inhalation device system of claim 13, wherein the opening of the blocking unit is located at the upstream end of the blocking unit.

15. An inhalation device system according to any preceding claim, wherein the counting unit comprises a counting mechanism and an activation mechanism.

16. An inhalation device system according to any preceding claim, wherein the activation mechanism interacts with a blocking mechanism of the blocking unit.

17. An inhalation device system according to any preceding claim, wherein the activation mechanism comprises an activation member (in the form of a pin) for interacting with the blocking mechanism of the blocking unit.

18. The inhalation device system of claim 17, wherein the activation member of the counting unit enters the opening of the blocking unit to interact with the blocking mechanism when the replaceable reservoir moves from the rest position to the activated position.

19. An inhalation device system according to item 17 or 18, wherein the position of the activation member is controlled by a counting mechanism.

20. An inhalation device system according to any preceding claim, wherein the counting mechanism operates by (physical/mechanical) interaction with the blocking unit when the exchangeable reservoir is moved from the rest position to the activated position.

21. An inhaler device system according to any preceding claim, wherein the counting mechanism comprises an index device to indicate the number of actuations of the inhaler device system (after insertion of the replaceable cartridge).

22. An inhalation device system according to any preceding claim, wherein the counting mechanism comprises a rotatable member having a (circular) inclined ramp on which the activation member is supported.

23. An inhalation device system according to any preceding claim, wherein the blocking unit comprises a blocking member which is initially activated in order to be able to "transition" to a blocking state (after insertion of the replaceable cartridge) upon interaction with the counting mechanism after a defined number of actuations of the inhalation device system.

24. An inhalation device system according to any preceding claim, wherein the blocking member of the blocking unit moves to the blocking position when a defined number of actuations is reached (after insertion of the exchangeable reservoir into the inhalation device).

25. Inhalation device system (10) according to any of the preceding claims, wherein the exchangeable reservoir is provided in the form of a cartridge with an outer (dimensionally stable) housing comprising an inner container for containing the medically active liquid in the form of a bag, in particular in the form of a collapsible bag.

26. The inhalation device system (10) according to any one of claims 10 to 25, wherein the force required to remove the blocking unit from the exchangeable reservoir is higher than the force required to remove the exchangeable reservoir from the receiving unit (23) of the inhalation device (20).

27. The inhalation device system (10) according to any one of the preceding claims, wherein the exchangeable reservoir comprising the blocking unit has a cylindrical shape with a central longitudinal axis (a) connecting a connection port (32) of the exchangeable reservoir (31) at the downstream end of the exchangeable reservoir (30) with the upstream end of the blocking unit attached to the upstream end of the exchangeable reservoir.

28. The inhalation device system (10) according to any one of the preceding claims, wherein the exchangeable reservoir (31) has an upstream end (34) and a downstream end (35), and wherein the connection port (32) is located at the downstream end (34) of the exchangeable reservoir (31), and wherein the extension of the blocking unit is attached to the upstream end (35) of the exchangeable reservoir.

29. The inhalation device system (10) according to any one of the preceding claims, wherein the blocking unit (33) is attached to the outer surface of the exchangeable reservoir (31) by a force fit connection or a form fit connection.

30. The inhalation device system (10) according to any one of the preceding claims, wherein the blocking unit (33) has substantially the same cross-sectional diameter as the exchangeable reservoir (31).

31. The inhalation device system (10) according to any one of the preceding claims, wherein the blocking unit (33) and the exchangeable reservoir (30) have a circular cross section.

32. The inhalation device system (10) according to any one of the preceding claims, wherein the (housing of the) barrier unit (33) has an opening (37) at the downstream end, the opening having a diameter corresponding to the (outer) diameter of the upstream end (34) of the exchangeable reservoir.

33. The inhalation device system (10) according to any one of the preceding claims, wherein the exchangeable reservoir (31) and the blocking unit (33) are assembled and sterilized before filling the cartridge system (30) with the medically active liquid.

34. The inhalation device system (10) according to any one of the preceding claims, wherein the replaceable reservoir (30) has an effective volume V selected in the range of about 0.1mL to about 15mL _e 。

35. The inhalation device system (10) according to any one of the preceding claims, wherein the pumping unit (40) of the inhalation device (20) comprises:

-an upstream end fluidly connected to a replaceable reservoir (30);

-a downstream end fluidly connected to a nozzle (25);

wherein the pumping unit further comprises:

(i) A standpipe (43) having an upstream end, wherein the standpipe (43) is adapted to act as a piston in a pumping unit and is fixedly attached to a user facing side of the housing (21) to be stationary relative to the housing (21); and

(ii) A hollow cylinder (41) located at an upstream end (44) of the standpipe, wherein the upstream end of the standpipe (43) is inserted into the cylinder (41) such that the cylinder (41) can move longitudinally on the standpipe (43).

36. The inhalation device system (10) of claim 35, wherein the pumping unit (40) comprises:

(iii) Lockable means (46) for storing potential energy when locked and releasing the stored energy when unlocked, the means (46) being arranged outside the cylinder (41) and mechanically engaged to the cylinder (41) such that unlocking the means (46) results in a pushing longitudinal movement of the cylinder (41) towards the downstream end of the pumping unit.

37. An inhaler system according to any preceding claim, wherein the inhaler is a hand-held inhaler.

38. An inhalation device system according to any preceding claim, wherein the inhalation device is a soft mist inhaler comprising at least one impact nozzle.

39. The inhalation device system of claim 38, wherein the at least one impingement nozzle comprises at least two channels to eject at least two streams of a medically active liquid, wherein the at least two liquid channels are oriented such that the trajectories of the at least two streams intersect at least one point of impingement.

40. An inhaler device system according to any preceding claim, wherein the inhaler device system and/or the pharmaceutically active liquid does not comprise a propellant, such as a Hydrofluorocarbon (HFC) propellant.

41. A replaceable cartridge system (30) for containing a medically active liquid for nebulization and being adapted for use in an inhalation device system (10) according to any of the preceding claims, wherein the cartridge system comprises: a container portion having an effective volume V for containing a medically active liquid _e The method comprises the steps of carrying out a first treatment on the surface of the And is connected withA connection port adapted to releasably fluidly connect the cartridge system to the pumping unit, in particular via a connection unit of a receiving unit of an inhalation device, wherein the blocking unit is connected to an upstream end of the container portion.

Detailed description of the drawings

The invention will be further described with reference to the accompanying drawings. The accompanying drawings illustrate specific, but non-limiting, embodiments of the invention.

Fig. 1 shows an inhalation device system (10) according to the prior art comprising an inhalation device (20) and a replaceable reservoir in the form of a cartridge system (30) inserted into the inhalation device (wherein the different elements of the cartridge system are not shown). The inhalation device (20) comprises a housing (21) having a lower portion (22) which can be detached from the inhalation device (20) and removed to open the housing (21) and allow access to a receiving unit (23) into which a replaceable cartridge system (30) can be inserted. Furthermore, the receiving unit (23) has a connection unit (24) adapted to be releasably fluidly connected to a connection port (32) of the exchangeable reservoir.

The inhalation device (20) also has a nozzle (25) at the downstream end of the inhalation device to atomize the medically active liquid. The inhalation device further has a pumping unit (40) arranged within the housing (21). As described in detail above, the pumping unit (via the connection unit (24) of the receiving unit (23)) is fluidly connected to the reservoir and to the nozzle (25) and is adapted to pump the medically active liquid from the reservoir (30) to the nozzle (25) in a downstream direction.

The pumping unit (40) comprises: an upstream end (41) fluidly connected to the replaceable reservoir (30); a downstream end (42) fluidly connected to the nozzle (25); wherein the pumping unit (40) further comprises: (i) A standpipe (43) having an upstream end (44), wherein the standpipe (43) is adapted to act as a piston in the pumping unit (40), and wherein the standpipe (43) is fixedly attached to a user facing (downstream) side of the housing (21) so as to be stationary relative to the housing (21); and (ii) a hollow cylinder (45) located upstream of the standpipe (43), wherein an upstream end (44) of the standpipe is inserted into the cylinder (45) such that the cylinder (45) can move longitudinally on the standpipe (43).

As shown in fig. 1, the pumping unit (40) further includes: (iii) Lockable means (46) for storing potential energy when locked and releasing the stored energy when unlocked, the means (46) being arranged outside the cylinder (45) and mechanically engaged with the cylinder (45) such that unlocking the means (46) results in a pushing longitudinal movement of the cylinder (45) towards the downstream end (42) of the pumping unit.

Fig. 2 shows an exemplary embodiment of an inhalation device system (10) according to the present invention in a fully assembled state. The inhalation device system comprises an inhalation device (20) having a plug-in exchangeable reservoir in the form of a cartridge system (30). In this particular embodiment, the inhalation device comprises a counting unit (32), while the cartridge system of the reservoir comprises a blocking unit (33).

The counting unit is part of a lower housing part (22) of the inhalation device (20). The housing lower portion (22) may be removably detached or opened, such as by a hinge (not shown).

The cartridge system (30) comprises a blocking unit (33) adapted to interact with the counting unit (32).

Fig. 3 shows a schematic view of the lower part (22) of the housing without the upper part of the housing. The counting unit (32) is located in a removable base (27) of the inhalation device system. The replaceable cartridge system (30) comprises a container portion (31) and a blocking unit (33). The blocking unit (33) is physically separated from the counting unit (32) and comprises a counting member (65) capable of interacting with the counting unit.

Fig. 4A to 4C show an exemplary embodiment of a counting unit (32) according to the invention. Fig. 4A shows a view of the inside of the housing (51) of the counting unit, and shows the counting unit in an assembled state. Fig. 4B shows a detailed view of the components of the counting unit, and fig. 4C shows the counting unit assembled without the inhalation device.

The counting unit (32) comprises a housing (51) in which the counting mechanism is located. The counting mechanism includes a movable sled (54) that drives a counting gear (53) to move an indicator member (55) including face teeth (face teeth) and an inclined ramp (58). An index device (56) is provided on the outside of the indicator member (55) to indicate the number of uses of the inhalation device system. The counting unit further comprises an activating member (52) which is movable on the inclined ramp to an increased height based on the position on the inclined ramp. The activation member is adapted to interact with the blocking mechanism.

Fig. 5 shows an overview of an embodiment of a cartridge system according to the invention, comprising a blocking unit according to the invention. Fig. 5A shows a container part (31) of a cartridge system, which container part may be connected to a housing (61) of a blocking unit comprising a counting member (65) for interaction with the counting unit. The blocking system includes a plunger (62) and a cam (63) that can interact with and be retained by a spring (64) mechanism.

Fig. 5B shows the interior of the housing (62) of the blocking unit, which housing comprises a protrusion (66) which limits the movement of the plunger (62) and the cam (63) depending on the state of the blocking unit.

Fig. 6A to 6C show embodiments of a counting mechanism and possible interactions of a blocking unit with a counting unit. Figure 6A shows the inhalation device system in a resting position. The counting member of the blocking system is above the opening of the counting unit and does not interact with the counting unit. The movable sled (54) of the counting mechanism is in an intermediate position. The position of the activation member (52) on the inclined ramp (58) of the indicator member (55) depends on the number of previous uses. Fig. 6A shows an early stage shortly after insertion of a new exchangeable reservoir, wherein the activation member (62) is located in a lower position on the inclined ramp.

Figure 6B shows the inhalation device system in the activated position. The counting member (65) of the blocking unit has entered the opening (57) of the counting unit, thereby moving the movable sledge (54). The movement of the movable sled drives a counter gear (53), which in turn moves an indicator member (55) such that an index device (56) advances and an activation member (52) moves up an inclined ramp. Fig. 6B further shows that the activation member does not interact with the blocking unit until a predetermined number of uses is reached.

Fig. 6C shows the counter unit and the blocking unit interacting after a predetermined number of uses. The activation member (52) has moved on the inclined ramp (58) and is now able to interact with the blocking unit by interacting with the plunger (62).

Fig. 7A to 7D show alternative embodiments of the counting mechanism. The counting mechanism includes an activation member (52) that is placed on an inclined ramp (58) to interact with the blocking mechanism after a predetermined number of activations.

Fig. 7A shows the counting mechanism through a section of the housing (51), and fig. 7B shows the counting mechanism in section. Fig. 7C shows the internal components of the housing (51) and the activation member (52) placed on the inclined ramp (58).

Fig. 7D shows the components of the counting mechanism separated.

An alternative counting mechanism includes a drive member (57) instead of a movable sled (54). The drive member comprises a helical guide thread (70) and radially arranged gear teeth (69). The helical guide thread (69) interacts with a guide member (68) arranged at the housing (51) of the counting unit. The drive member is movable and is capable of returning to its original position by means of a spring (64).

In order to activate the counter unit, the counter member (55) of the blocking unit enters the opening (57) of the housing (51) and moves the drive member (67). The drive member is guided by a guide member (68) to move a gear (53), which in turn moves the indexing means (56), thereby also moving the activation member along the inclined ramp (58) until the activation member interacts with the blocking unit. In some embodiments, it is also possible for the drive member to directly move the indexing means.

Fig. 8A to 8C show an embodiment of the blocking mechanism. Fig. 8A shows the blocking mechanism in an initial position, wherein the cam (63) is held in place by a protrusion (66) inside the housing (61) of the blocking unit. The plunger (62) is movable within the cam (63) and is activatable by the activating member (52) of the counting unit. The cam and plunger are held in place by a spring (not shown).

Fig. 8B and 8C illustrate the activation of the blocking mechanism. After activation of the activation member (52) of the counting unit, the plunger (62) will move and activate the cam (63), thereby removing the cam from the protrusion (66) (fig. 8B). Due to a spring mechanism (not shown), the cam (62) will move along the projection (66) to a blocking position (fig. 8C) preventing further movement of the plunger (62) and cam (63). In this case, the activation member (52) of the counting unit prevents further movement of the cartridge, thereby preventing further use of the cartridge.

List of reference numerals

10. Inhalation device system

20. Inhalation device

21. Shell body

22. Lower part of the housing

23. Receiving unit

24. Connection unit

25. Nozzle

26. Cover

27. Removable base

30. Replaceable cartridge system

31. Container portion

32. Counting unit

33. Barrier unit

40. Pumping unit

41. Upstream end of pumping unit

42. Downstream end of pumping unit

43. Vertical pipe

44. Upstream end of riser

45. Hollow cylinder of pumping unit

46 lockable device for storing potential energy

51. Shell of counting unit

52. Activating member

53. Gear wheel

54. Movable skid

55 indicator member with sloped ramp and face teeth

56. Index device

57. An opening

58. Inclined slope

61. Housing of a blocking unit

62. Plunger piston

63. Cam

64. Spring

65. Counting component

66. Protrusions

67. Driving member

68. Guide member

69. Gear teeth

70. Spiral guide thread

Claims

wherein the inhalation device (20) comprises:

-a housing (21) having a receiving unit (23) with a connection unit (24) adapted to be releasably fluidly connected to a connection port (31) of the exchangeable reservoir (30), the receiving unit (24) being adapted to receive the exchangeable reservoir (30) and to be fluidly connected to the exchangeable reservoir (30);

-a nozzle (25) for atomizing the medically active liquid; and

a pumping unit (40) arranged within the housing (21) adapted to be fluidly connected to the exchangeable reservoir (30) and the nozzle (25), adapted to transfer the medically active liquid from the exchangeable reservoir (30) to the nozzle (25) in a downstream direction, and adapted to move the exchangeable reservoir from a rest position to an activated position upon activation of the pumping unit,

it is characterized in that the method comprises the steps of,

the inhalation device system includes a combined count and block assembly comprising: a counting unit for counting the number of actuations of the inhalation device system (after insertion of the exchangeable reservoir into the inhalation device); and a blocking unit for blocking the movement of the exchangeable reservoir from the rest position to the activated position when a defined number of actuations is reached (after insertion of the exchangeable reservoir into the inhalation device),

wherein the counter unit and the blocking unit are physically separated from each other when the replaceable cartridge is in the rest position, and the counter unit and the blocking unit are adapted to (physically) interact with each other each time the replaceable cartridge is moved from the rest position to the activated position,

Wherein the blocking unit is attached to the replaceable reservoir and the counting unit is attached to the housing of the inhalation device; or alternatively

The counting unit is attached to the replaceable reservoir and the blocking unit is attached to the housing of the inhalation device.

2. The inhalation device system of claim 1, wherein the counting unit is attached to the housing of the inhalation device, and wherein the blocking unit is attached to the replaceable reservoir.

3. An inhalation device system according to any preceding claim, wherein the replaceable reservoir is in the form of a replaceable cartridge having an upstream end and a downstream end, and a blocking unit is attached to the upstream end of the replaceable cartridge.

4. An inhalation device system as claimed in any preceding claim, wherein the blocking unit has a housing containing a blocking mechanism.

5. The inhalation device system of claim 4, wherein the housing of the blocking unit comprises an opening for interaction between the counting unit and the blocking mechanism.

6. An inhalation device system according to any preceding claim, wherein the counting unit comprises a counting mechanism and an activation mechanism.

7. An inhalation device system according to any preceding claim, wherein the activation mechanism interacts with the blocking mechanism of the blocking unit.

8. An inhalation device system according to any preceding claim, wherein the activation mechanism comprises an activation member for interacting with the blocking mechanism of the blocking unit, wherein the activation member is movable and the position of the activation member changes with each actuation of the inhaler device system.

9. The inhalation device system of claim 8, wherein the activation member is moved gradually or stepwise with each actuation.

10. An inhalation device system according to claim 8 or 9, wherein the activation member of the blocking unit enters the opening of the blocking unit to interact with the blocking mechanism when the exchangeable reservoir is moved from the rest position to the activated position.

11. An inhalation device system according to any preceding claim, wherein the counting mechanism operates by interaction with the blocking unit as the exchangeable reservoir moves from the rest position to the activated position.

12. An inhalation device system according to any preceding claim, wherein the blocking unit comprises a blocking mechanism which limits the space of the activation member after a predetermined number of uses such that the exchangeable reservoir can no longer be moved to the activated position.

13. A replaceable cartridge system for an inhalation device system comprising a combined counting and blocking assembly according to any one of claims 1 to 12, for containing a medically active liquid for nebulization and adapted for use in an inhalation device system according to any one of the preceding claims, wherein the cartridge system comprises: a container portion having an effective volume V for containing the medically active liquid _e The method comprises the steps of carrying out a first treatment on the surface of the And a connection port adapted to releasably fluidly connect the cartridge system to the pumping unit, in particular via the connection unit of the receiving unit of the inhalation device, wherein the cartridge system comprises a blocking unit adapted to interact with a counting unit of an inhalation device comprising a combined counting and blocking assembly according to any one of claims 1 to 12.

14. An inhalation device for an inhalation device system comprising a combined counting and blocking assembly according to any one of claims 1 to 12, wherein the inhalation device comprises:

-a housing having a receiving unit with a connection unit adapted to be releasably fluidly connected to a connection port of the exchangeable reservoir, the receiving unit being adapted to receive the exchangeable reservoir and to be fluidly connected to the exchangeable reservoir;

-a nozzle for atomizing the medically active liquid; and

a pumping unit arranged within the housing, adapted to be fluidly connected to the nozzle and the exchangeable reservoir, adapted to deliver the medically active liquid from the exchangeable reservoir to the nozzle (in a downstream direction), and adapted to move the exchangeable reservoir from a rest position to an activated position upon activation of the pumping unit,

wherein the inhalation device comprises at least one of the following:

-a counting unit adapted to interact with a blocking unit of a combined counting and blocking assembly according to any one of claims 1 to 12; and/or

-a blocking unit adapted to interact with a counting unit of a combined counting and blocking assembly according to any one of claims 1 to 12.