Suction device with integral piston

Abstract

The present invention provides a handheld inhalation device for administering a medically active fluid (F) in atomized (vaporised) form for inhalation therapy, comprising: (a) a housing (1) having a user-facing side; (b) a nozzle (6) for generating an atomized aerosol by collision of at least two liquid jets, the nozzle (6) being securely attached to a user-facing side of the housing (1) so as to be stationary relative to the housing (1); (c) a fluid reservoir (2) arranged within the housing (1) for containing a medically active fluid; and (d) a pumping unit arranged within the housing (1), while the pumping unit comprises a riser and a holder in the form of a one-piece unit.

Description

Technical Field

[0001] This invention relates to the field of inhalation devices for delivering atomized medical active fluids for inhalation therapy. Specifically, this invention relates to handheld inhalation devices including a pumping unit having a riser and a corresponding retainer in a one-piece unit form. The invention also relates to a corresponding method. Background Technology

[0002] Pumping devices or units for use in medical devices, specifically for pumping medical fluids, are well known in the art. For example, such devices are found in inhalation devices for administering medical fluids or active ingredients in aerosol form (i.e., small droplets embedded in a gas). Such inhalation devices are described, for example, in document WO 91 / 14468 A1. Essential components of such an inhalation device are: a reservoir containing the liquid to be atomized; a pumping device for generating sufficient pressure for atomization; and a spraying device in the form of a nozzle. By means of the pumping device, the liquid is drawn from the reservoir in discrete amounts (i.e., discontinuously) and supplied to the nozzle. The pumping device operates without a propellant and generates pressure mechanically.

[0003] The document further discloses the following embodiment: Pressure in the pumping chamber connected to the housing is generated by the movement of a movable hollow piston. The piston is movably arranged inside a stationary cylinder or pumping chamber. The upstream inlet of the hollow piston is fluidly connected to the interior of a reservoir (reservoir piping section). The downstream end of the hollow piston leads to the pumping chamber. Furthermore, a check valve to prevent liquid backflow into the reservoir is arranged inside the end of the piston.

[0004] To fill the piston, it is directly connected to the reservoir via its upstream end. By pulling out the piston of the pumping chamber located inside the hollow cylinder, the internal volume of the pumping chamber is expanded, resulting in insufficient increased pressure to build up inside the pumping chamber. This pressure is transmitted through the hollow piston to the reservoir, causing liquid to be drawn from the reservoir into the piston. Simultaneously, the valve mentioned above opens at its end because the pressure inside the reservoir is higher than the pressure inside the (still empty) pumping chamber. The pumping chamber is being filled. Meanwhile, a spring is loaded, and when the movable piston has reached its bottom dead center (in the case of a vertically arranged device) and the pumping chamber is fully filled, the spring is locked at the end of its movement.

[0005] Further examples of pumping devices are disclosed in US 2014 / 0076308 A1 for generating discrete quantities of medical fluid in pressurized form for inhalation. This document discloses a particular inhaler having a pumping unit with a pressure chamber and a delivery tube serving as a piston within the pressure chamber. The delivery tube has a one-way valve located at its downstream end within the pressure chamber.

[0006] The piston is housed within a compression spring designed as a helical spring, which limits its outer diameter. Furthermore, due to its typically small size (e.g., 15µl), the piston is designed with a small inner diameter (which is also usually the outer diameter).

[0007] The typically small internal diameter of the delivery pipe (or, in other words, the movable piston), for example, 0.3 mm to 1.0 mm, coupled with the small size of the check valve disposed therein, is a disadvantage of the described construction. The small diameter results in high flow resistance, meaning that, in particular, higher viscosity media can only flow in and through the piston very slowly. In other words, the described construction is particularly suitable for low-viscosity (aqueous) liquids and for injecting low doses of such liquids. Furthermore, manufacturing a sufficiently tight small-diameter check valve presents difficulties.

[0008] WO 2018 / 197730 A1 discloses an improved suction device utilizing a non-movable piston. This device overcomes some of the disadvantages of the aforementioned prior art.

[0009] Furthermore, the pumping unit of the aforementioned device is designed to generate discrete portions of the medical fluid to be atomized under the high pressure conditions necessary for atomizing the corresponding medical fluid, typically in the range of about 10 bar to about 100 bar and above. Therefore, the components corresponding to the pumping unit, particularly the corresponding piston used to generate pressure, are made of mechanically stable and pressure-resistant materials, typically metals such as stainless steel.

[0010] However, this is particularly relevant to the aforementioned space constraints and results in the need for precisely machined metal parts, which significantly increases the overall manufacturing cost of the device, especially for devices used in a limited number of times.

[0011] Therefore, the object of the present invention is to provide an improved high-pressure medical pumping device for providing discrete portions of pressurized medical fluids, which overcomes at least one of the aforementioned disadvantages of prior art devices. Further objects of the invention will become clear based on the following description, examples, and claims. Summary of the Invention

[0012] In a first aspect, the present invention relates to a handheld inhalation device for delivering a medically active fluid (F) in nebulized form for inhalation therapy, comprising: (a) A housing (1) having a side facing the user; (b) Nozzle (6) for generating atomized aerosol by the collision of at least two liquid jets, nozzle (6) being securely attached to the user-facing side of housing (1) so as to be fixed relative to housing (1); (c) A fluid reservoir (2), arranged within the housing (1), for containing medically active fluids; and (d) A pumping unit, arranged within the housing (1), the pumping unit having: -The upstream end, which is fluidly connected to the fluid reservoir (2); and - Downstream end, which is fluidly connected to the nozzle (6). The pumping unit is adapted to pump medical active fluid (F) from the fluid reservoir (2) to the nozzle (6). The pumping unit further includes: (i) A riser (5) having an upstream end and a downstream end, wherein the riser (5) is adapted to be used as a piston in a pumping unit; (ii) A retainer (10) located downstream of the riser and securely attached to the user-facing side of the housing (1) to be fixed relative to the housing (1) for retaining the riser; (iii) A hollow cylinder (9) located upstream of a riser (5), wherein the upstream end of the riser (5) is inserted into the cylinder (9) such that the cylinder (9) can move longitudinally on the riser (5); and (iv) A lockable device (7) for storing potential energy, which stores potential energy when locked and releases the stored energy when unlocked, the device (7) being arranged outside the cylinder (9) and mechanically coupled to the cylinder (9) such that the unlocking device (7) allows the cylinder (9) to move longitudinally toward the downstream end of the pumping unit. Among them, the retainer (10) and the riser (5) are one-piece units.

[0013] In a specific embodiment of the first aspect, the present invention provides a handheld inhalation device for delivering a nebulized medical active fluid (F) for inhalation therapy, comprising: (a) A housing (1) having a user-facing side, the housing further comprising a container configured for attaching a riser (5); (b) Nozzle (6) for generating atomized aerosol by the collision of at least two liquid jets, the nozzle (6) being securely attached to the user-facing side of the housing (1) so as to be fixed relative to the housing (1); (c) A fluid reservoir (2), arranged within the housing (1), for containing medically active fluids; and (d) A pumping unit, arranged within the housing (1), the pumping unit having: -The upstream end, which is fluidly connected to the fluid reservoir (2); and - Downstream end, which is fluidly connected to the nozzle (6). The pumping unit is adapted to pump medical active fluid (F) from the fluid reservoir (2) to the nozzle (6). The pumping unit further includes: (i) Riser (5), which as a whole includes: The riser section has an upstream end and a downstream end; The retainer section (10), located at the downstream end of the riser section, is attached to the container of the housing and securely attaches the riser (5) to the user-facing side of the housing (1) so as to be fixed relative to the housing (1). (ii) A hollow cylinder (9) located upstream of a riser (5), wherein the upstream end of the riser (5) is inserted into the cylinder (9) such that the cylinder (9) can move longitudinally along the riser section; and (iii) A lockable device (7) for storing potential energy, which stores potential energy when locked and releases the stored energy when unlocked, the device (7) being arranged outside the cylinder (9) and mechanically connected to the cylinder (9) such that the unlocking device (7) allows the cylinder (9) to be moved longitudinally toward the downstream end of the pumping unit.

[0014] In a second aspect, the present invention provides a one-piece unit comprising a riser and a retainer, which is adapted to be incorporated into an inhalation device according to a first aspect of the present invention.

[0015] In a third aspect, the present invention provides a method for manufacturing a one-piece unit according to a second aspect of the present invention, wherein the method comprises injection molding of an injection-moldable material.

[0016] In a fourth aspect, the present invention provides a method for generating a mist-like aerosol of a medically active liquid. This method may involve using, in any embodiment thereof, an inhalation device as described in the first aspect of the present invention above. Attached Figure Description

[0017] Figure 1 An embodiment of the inhalation device according to the invention before its first use is illustrated schematically.

[0018] Figure 2 It shows the relationship with Figure 1 It is a device similar to the one in the device, but without an outlet valve.

[0019] Figure 3 It shows Figure 1 In one embodiment, the pumping chamber has been filled.

[0020] Figure 4 The situation during the first actuation of the device is shown.

[0021] Figure 5 The result shows the situation at the end of the first actuation.

[0022] Figure 6 The image shows the situation after the pump chamber has been refilled.

[0023] Figure 7 Another embodiment of the inhalation device according to the invention is depicted, which includes a riser and a retainer configured as a one-piece structure.

[0024] Figures 8 to 10 An embodiment of a high-pressure medical pumping device for providing discrete portions of a pressurized medical fluid (F) is depicted.

[0025] Figures 11 to 13 Alternative embodiments of a high-pressure medical pumping device for providing discrete portions of a pressurized medical fluid (F) are described. Detailed Implementation

[0026] Unless otherwise defined in the specification, or unless the specific context indicates or requires otherwise, the following terms or expressions used herein shall generally be interpreted as set forth in this section: The terms “comprise,” “comprises,” and “comprising,” as well as similar expressions, should be interpreted in an open-ended and inclusive manner as “including, but not limited to,” the terms “consist of,” “consists of,” and “consisting of” as used herein are so-called closed-ended languages, meaning that only the mentioned components exist.

[0027] The terms “a” or “an” do not exclude multiple; that is, the singular forms “a,” “an,” and “the” should be understood to include the plural referent unless the context clearly indicates or requires otherwise. In other words, all references to the singular feature or limitation in this disclosure should include the corresponding plural feature or limitation, and vice versa, unless otherwise expressly stated or implied to the contrary in the context of the reference. The terms “a,” “an,” and “the” therefore have the same meaning as “at least one” or “one or more”, unless otherwise defined.

[0028] The terms "one embodiment," "an embodiment," and "specific embodiment" mean that a particular feature, property, or characteristic, or a particular set or combination of features, properties, or characteristics, exists in at least one embodiment of the invention when referenced in conjunction with the corresponding term. These terms appearing in different places throughout the specification do not necessarily refer to the same embodiment. Furthermore, in one or more embodiments, a particular feature, property, or characteristic may be combined in any suitable manner.

[0029] Terms such as “substantially,” “about,” “approximately,” and “generally” associated with attributes or numerical values ​​include exact attributes or precise numerical values, as well as any attribute or numerical value that is generally considered to fall within the normal range or variability acceptable in the relevant technical field. For example, the term “about” as used herein associated with a numerical value or range of numerical values ​​should mean that the numerical value or range of numerical values ​​contains a typical deviation from the numerical value by a maximum of + / - 5% (absolute value), or a maximum of about + / - 4%, or a maximum of + / - 3%, a maximum of + / - 2%, a maximum of + / - 1%, or a maximum of + / - 0.5%.

[0030] According to a first aspect of the invention, the invention provides a handheld inhalation device for delivering atomized, or in other words, atomized medical active fluid for inhalation therapy.

[0031] More specifically, the device includes a housing having a user-facing side, a nozzle (specifically, an impingement nozzle as described further below) for generating an atomized aerosol through the collision of at least two liquid jets, a fluid reservoir disposed within the housing for containing a medically active fluid, and a pumping unit also disposed within the housing. The nozzle is securely attached, or in other words, attached to the user-facing side of the housing for fixation relative to the housing. The pumping unit has an upstream end fluidly connected to the fluid reservoir and a downstream end fluidly connected to the nozzle. Furthermore, the pumping unit is adapted to pump the medically active fluid from the fluid reservoir to the nozzle, and includes a riser adapted to function as a piston in the pumping unit, a retainer for retaining the riser located downstream of the riser, or more specifically, at the downstream end of the riser, and securely attached to the user-facing side of the housing for fixation relative to the housing. The pumping unit further includes a hollow cylinder and a lockable device for storing potential energy.

[0032] The riser is securely attached to the user-facing side of the housing so as to be fixed relative to the housing via a retainer. In the context of this invention, the term "retainer" refers to a structural element integrated with the downstream end of the riser, which engages with other features of the handheld inhaler, such as those for attachment to the housing. Thus, the retainer provides a stable and fixed position for the riser relative to other components of the handheld inhaler. Typically, the retainer is wider than the diameter of the riser and preferably includes features for attachment and / or fixation to other parts of the inhaler.

[0033] A hollow cylinder is located upstream of the riser, and the upstream end of the riser is inserted into the cylinder, allowing the cylinder to move longitudinally along the riser. A lockable device is capable of storing potential energy when locked and is adapted to release the stored energy when unlocked. This device is arranged outside the cylinder and mechanically coupled to it, such that unlocking the device allows the cylinder to move longitudinally in a propulsive manner toward the downstream end of the pumping unit. According to the invention, the retainer and the riser are a single unit, or in other words, an integral single unit, or in other words, provided in a form that prevents them from being separated from each other in a reversible or non-destructive manner. Thus, the retainer for retaining the riser and securing it relative to the rest of the pumping unit and the suction device is in the form of a single unit, wherein the riser and the retainer cannot be removed from each other in a non-destructive and reversible manner.

[0034] As used herein, a handheld inhalation device is a mobile device that can be easily held in one hand and is suitable for delivering a nebulized medical-active aerosol for inhalation therapy. For suitability for inhalation therapy, the device must be able to spray a medical-active aerosol with a particle size that is inhalable, i.e., small enough to be absorbed by the lungs of a patient or user. Typically, the mass median aerodynamic diameter of the inhalable particles does not exceed about 10 μm, particularly not more than about 7 μm, or not more than about 5 μm. In this respect, this inhalation device differs significantly from devices that spray nebulizers for oral or nasal administration (such as those disclosed in US 2004 / 0068222 A1).

[0035] According to the present invention, the inhalation device is capable of delivering atomized aerosols, particularly for delivering medically active fluids in atomized form. As used herein, an aerosol is a system having at least two phases: a continuous phase, which is gaseous, and a dispersed liquid phase comprising small droplets. Optionally, the liquid phase itself may be a liquid solution, dispersion, suspension, or emulsion.

[0036] The term "medically active fluid" as used herein should be interpreted broadly and refers to fluids or preferred liquids that can be administered to a subject, for example, by inhalation or oral administration, and which are preferably physiologically and / or pharmaceutically acceptable. In some embodiments, a medically active fluid may be water or another physiologically and / or pharmaceutically acceptable liquid compound or mixture of liquid compounds, or a liquid composition comprising one or more physiologically and / or pharmaceutically acceptable liquid components, such as solutions or dispersions. In some embodiments, a medically active fluid may be a liquid composition comprising an aqueous or alcoholic liquid solvent, or in other words, a vehicle, and optionally at least one medically active ingredient and optionally at least one pharmaceutically acceptable excipient, wherein the term "excipient" as used herein refers to compounds that may be included in a medically active fluid, including, but not limited to, one or more buffers (such as hydrochloric acid), chelating agents (such as EDTA), salts (such as sodium chloride), masking agents, surfactants, lipids, antioxidants, and cosolvents that may be used to enhance or improve solubility, and preservatives (such as benzalkonium chloride) for adjusting or controlling the pH of the solution.

[0037] Suitable excipients are known to those skilled in the art and are described, for example, in standard pharmacopoeias such as the United States Pharmacopeia or the European Pharmacopoeia, or in Handbook of Pharmaceutical Excipients, 6th ed. Rowe et al., Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009.

[0038] In some embodiments, the medically active fluid may be simply water or an aqueous solution of sodium chloride. In further embodiments, the medically active fluid may include at least one active pharmaceutical ingredient, such as those selected from the group consisting of: long-acting muscarinic antagonists (LAMAs), such as tiotropium, aclidinium, umeclidinium, and glycopyrrolium; or long-acting beta-antagonists (LABAs), such as olodaterol and vilanterol; or inhaled corticosteroids (ICS), such as prednisolone, cistanoic acid, beclomethasone, etc.

[0039] For the generation of atomized aerosols, a suitable nozzle is important. In some embodiments of the inhalation device of the present invention, the nozzle is an impact nozzle. This means that the nozzle is adapted to spray at least two liquid jets that are guided to collide and break into small aerosol droplets. The nozzle is securely attached to the user-facing side of the housing of the inhalation device in such a way that, when the device is used, the nozzle is fixed or immovable relative to the housing or at least relative to the user-facing (e.g., patient-facing) side or portion of the housing.

[0040] A fluid reservoir arranged within the housing is adapted to contain or store a medically active fluid or liquid from which an aerosol is generated and delivered by an inhalation device.

[0041] The pumping unit, also arranged within the housing, is suitable for use as a piston pump, also known as a plunger pump, wherein the riser acts as a piston or plunger that can move longitudinally within the hollow cylinder. The inner section of the hollow cylinder—in which the upstream end of the riser moves—forms a pumping chamber whose volume varies depending on the position of the riser relative to the cylinder.

[0042] The hollow cylinder providing the pumping chamber is fluidly connected directly or indirectly to the fluid reservoir, for example by means of an optional reservoir conduit (or reservoir conduit section). Similarly, the riser—whose inner (upstream) end facing the reservoir may be housed in the hollow cylinder—is fluidly connected directly or indirectly in a liquid-tight manner to the nozzle at its downstream or outer end.

[0043] In the context of this document, the term "hollow cylinder" refers to a hollow portion or component in the sense that its internal voids have a cylindrical shape or that have sections containing cylindrical spaces. In other words, and applicable to other types of piston pumps, it does not require the external shape of the corresponding portion or component to be cylindrical. Furthermore, the term "hollow cylinder" does not preclude the following operating state of the corresponding portion or component: in which the "hollow" space may be filled with material, such as a liquid to be atomized.

[0044] As used in this article, longitudinal movement means movement along the main axis of the hollow cylinder, while propulsive movement is movement in part in the downstream (or forward) direction.

[0045] Importantly, the riser of the pumping unit of the inhalation device of the present invention is arranged downstream of the cylinder and is securely attached to the user-facing side of the housing via a retainer described further below, so as to be fixed relative to the housing or at least relative to the portion of the housing including the user-facing side. For the avoidance of doubt, the term "securely fixed" means fixed directly or indirectly (i.e., via one or more connecting parts) to prevent relative movement between the parts. Since the nozzle is also fixed relative to the housing or a corresponding portion of the housing, the riser is also fixed relative to the nozzle, and the pumping action is affected by the longitudinal movement of the hollow cylinder. Propulsive movement of the cylinder relative to the riser, positioned upstream, results in a decrease in the volume of the pumping chamber, while repulsive movement of the cylinder results in an increase in volume. In other words, the riser maintains its position relative to the housing, thus allowing the hollow cylinder to change its position relative to the housing, particularly along its longitudinal axis, so that the fixed riser can undergo piston-in-cylinder-type movement within the movable cylindrical member.

[0046] This arrangement differs from other impact-type suction devices, which rely on a pumping unit with a riser upstream and a cylindrical member downstream, where the riser is movable and the cylindrical member is fixed to the housing, as disclosed in US 2012 / 0090603 A1. A key advantage of the device design of this invention is that the passage between the pumping chamber and the fluid reservoir can be designed with fewer limitations in its size. For example, a significantly larger inlet valve (also called a check valve) can be accommodated, which is easier to manufacture because it does not have to be contained within a narrow riser. Conversely, the design of the suction device of this invention allows for the use of a check valve whose size is limited only by the internal size of the housing or the size of the device used to store potential energy. In other words, the diameters of the valve, riser, and reservoir piping (if used) do not need to be matched. Furthermore, since there is no need to connect a movable piston to the fluid reservoir, the components for fluid connection to the reservoir can be designed independently of the movable parts (i.e., the hollow cylinder), thus adapting each part to its respective independent function. In this respect, the design of the device of the present invention offers greater design flexibility because the movable hollow cylinder, due to its robust structure and size, provides better opportunities for designing a mechanically stable connection with the reservoir compared to a less robust movable riser. Furthermore, the connection between the hollow cylinder and the fluid reservoir can be designed with a larger diameter, making higher flow rates and fluid viscosities feasible. In addition, the support for the reservoir can be integrated into any component including the cylinder. Furthermore, any vent for reservoir pressure balancing can be moved from the reservoir body itself to (e.g.) a connector forming a joint between the reservoir and the hollow cylinder, thereby facilitating construction and avoiding the necessity of providing a substantially "open" reservoir body.

[0047] As described above, a lockable device for storing potential energy is adapted to store energy in its locked state and to release the stored energy when unlocked. The device is mechanically coupled to a hollow cylinder such that unlocking the device allows the cylinder to move longitudinally in a pushing motion toward 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. Conversely, when the device for storing potential energy is locked, the hollow cylinder is in its upstream position, where the volume of the pumping chamber is at its maximum. The locked state can also be considered the primed state. When the state of the device for storing energy changes from the unlocked state to the locked state—which can be referred to as priming the device—the hollow cylinder performs a pushing longitudinal movement, i.e., a longitudinal movement from its downstream position toward its upstream position. The pumping cycle consists of two successive and opposite movements of the cylinder: a movement from its downstream position to its upstream (or primed) position, and a movement back to its downstream position driven by the device for storing potential energy now releasing its energy.

[0048] In one preferred 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 between about 2 bar and about 1000 bar, or between about 50 bar and about 250 bar. In some embodiments, the operating pressure may be in the range of at least about 150 bar, at least about 175 bar, or at least about 200 bar, for example from about 100 bar to about 1000 bar or higher, or from at least about 125 bar, for example from about 125 bar to about 750 bar, or from at least about 150 bar, for example from about 150 bar to about 500 bar, or from at least about 175 bar, for example from about 175 bar to about 400 bar, or from at least about 200 bar, for example from about 200 bar to about 300 bar, or from about 100 bar or from about 150 bar to about 300 bar. As used herein, operating pressure is the pressure at which a pumping unit discharges fluid from its pumping chamber in a downstream direction (i.e., toward the nozzle), particularly a medically active fluid or liquid, such as an inhalable aqueous liquid formulation of a pharmacologically active ingredient. In this context, the expression "suitable for operation" means selecting components of the pumping unit in terms of materials, dimensions, surface quality, and finish to enable operation at a specific pressure.

[0049] Furthermore, this high-pressure pumping unit means that the device for storing potential energy can store and release a sufficient amount of energy to drive the propulsive longitudinal movement of the cylinder by a force that can obtain the corresponding pressure.

[0050] The device for storing potential energy can be designed as a tension spring or a compression spring. Alternatively, in addition to a metallic or plastic body, a gaseous medium or a material utilizing magnetic force can also be used as an energy storage device. Potential energy is supplied to the device through compression or tension. One end of the device can be supported at or in a suitable location within the housing; thus, this end can be substantially fixed. Through the other end, the device can be connected to a hollow cylinder providing a pumping chamber; thus, this end can be substantially movable. The device can be locked after being loaded with a sufficient amount of energy, so that the energy can be stored until unlocking occurs. When unlocked, the device can release potential energy (e.g., spring energy) into the cylinder having the pumping chamber, which is then driven to perform (in this case, longitudinal) movement. Typically, the energy release occurs abruptly, allowing high pressure to build up within the pumping chamber, followed by the ejection of a large volume of liquid, which causes a pressure drop. In fact, for a considerable portion of the ejection phase, there is a balance between the pressure supplied by the device for storing potential energy and the amount of liquid already ejected. Therefore, the amount of liquid remains substantially constant during this phase, which is a significant advantage for devices that use the user's manual force for dispensing, such as those disclosed in documents US 2005 / 0039738 A1, US 2009 / 0216183 A1, US 2004 / 0068222 A1, or US 2012 / 0298694 A1, because manual force depends on the individual user or patient and is likely to vary greatly during the dispensing phase, resulting in uneven droplet formation, size, and number. Compared to the prior art, the device according to the invention ensures that the inhalation device provides highly reproducible results.

[0051] Devices for storing potential energy can also be provided in the form of highly pressurized gas containers. Through proper arrangement of the highly pressurized gas container and repeatable intermittent start-up (opening), a portion of the energy stored within the gas container can be released into the cylinder. This process can be repeated until the remaining energy is insufficient to establish the desired pressure in the pumping chamber again. After this, the gas container must be refilled or replaced.

[0052] In one preferred embodiment, the device for storing potential energy is a spring having a load of at least 10 N in the deflected state. In a particularly preferred embodiment, the device for storing potential energy is a compression spring made of steel having a load of about 1 N to about 500 N in the deflected state. In other preferred embodiments, the compression spring made of steel has a load of about 2 N to about 200 N, or about 10 N to about 100 N, in the deflected state. In specific embodiments, for example, the spring may have a load of at least about 30 N, at least about 35 N, or at least about 40 N in the deflected state, or a load selected in the range of about 50 N to about 200 N, about 150 N, or about 100 N, or a load selected in the range of about 30 N to about 150 N, or about 100 N, in the deflected state, or a load selected in the range of about 35 N to about 80 N. In a further embodiment, the pumping unit may further include a locking member for locking the lockable device. This allows the drive unit to be tensioned or loaded, and in a separate step, the drive unit can be triggered by unlocking the lockable device for storing potential energy to drive the pumping unit.

[0053] The inhalation device according to the invention is preferably adapted to deliver atomized medically active aerosol in a discontinuous manner (i.e., in discrete units), wherein one unit is delivered per pumping cycle. In this respect, the device differs from common nebulizers, such as jet nebulizers, ultrasonic nebulizers, vibrating screen nebulizers, or electrohydrodynamic nebulizers, which typically produce and deliver atomized aerosol continuously over time intervals of seconds to minutes, requiring multiple continuous breathing actions for the aerosol to be inhaled by the patient or user. Instead, the inhalation device of the invention is adapted to produce and spray discrete units of aerosol, each unit corresponding to the amount (i.e., volume) of fluid (i.e., medically active fluid or liquid) pumped into the nozzle by the pumping unit in one pumping cycle, wherein the fluid is immediately atomized at the nozzle and delivered to the user or patient. Conversely, 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. Therefore, precise, reliable, and reproducible operation of the pumping unit is crucial for achieving the desired therapeutic effect.

[0054] In a preferred embodiment, a single dose of the drug (i.e., a mist of a medically active fluid or liquid) is contained in a single unit, that is, delivered from a pumping unit to the volume of a nozzle used to generate the aerosol in a single pumping cycle. In this case, the user or patient only needs to prime and actuate the device once per administration (i.e., per administration event) and inhale the released aerosol in one breathing action.

[0055] In another preferred embodiment, a single dose consists of two units of aerosol, thus requiring two pumping cycles. Typically, the user or patient will activate the device to release and inhale one unit of aerosol, and then repeat the process. Alternatively, three or more aerosol units can constitute a single dose.

[0056] The volume of fluid (e.g., medically active liquid) pumped by the pumping unit in a pumping cycle is preferably in the range of about 2 µL to about 150 µL. Specifically, this volume range can be between about 0.1 µL and about 1000 µL, or between about 1 µL and about 250 µL, or between about 1 µL and about 250 µL, or between about 2 µL and about 150 µL, or between about 5 µL and about 100 µL, or between about 10 µL and about 75 µL, or between about 15 µL and about 50 µL, or between about 20 µL and about 40 µL or about 30 µL, or between about 10 µL and about 30 µL or about 20 µL. This volume range is almost identical to the liquid phase volume contained in one unit of aerosol produced by the inhalation device, and may vary slightly due to minor liquid losses within the device.

[0057] In another preferred embodiment, the pumping unit includes an inlet valve, also referred to as a check valve or inlet check valve, positioned within or adjacent to the hollow cylinder. According to this embodiment, the internal space of the hollow cylinder (i.e., the pumping chamber) is fluidly connected to a fluid reservoir via the inlet check valve. The inlet valve allows liquid to flow into the pumping chamber but prevents backflow of liquid toward or into the fluid reservoir. The inlet valve can be located at or near the upstream end of the cylinder so that almost the entire internal volume of the hollow cylinder is available for use as the pumping chamber. Alternatively, the inlet valve can be positioned more centrally along the (longitudinal) main axis of the hollow cylinder to define an upstream section and a downstream section of the cylinder, the upstream section being upstream of the inlet valve and the downstream section downstream of the valve. In this case, the pumping chamber is located in the downstream section.

[0058] As described above, one of the advantages of the inhalation device design of the present invention is that a relatively large inlet valve can be accommodated in this location, namely at the upstream end of the pumping chamber. This is particularly advantageous because it allows for a larger fluid conduit within the valve, thereby enabling high fluid velocities and rapid filling of the pumping chamber during inhalation device startup. Furthermore, it becomes feasible to use liquids with a viscosity higher than that of conventional inhalation liquid formulations (e.g., highly concentrated solutions of soluble active ingredients) for inhalation therapy.

[0059] According to some embodiments, the inlet valve can be adapted to open only when the pressure difference between the upstream and downstream sides of the valve (i.e., the fluid reservoir side and the pump chamber side) is higher than a predetermined threshold, and remain closed as long as the pressure difference is below that threshold. The term "pressure difference" as used in this context refers to the relative pressure difference between the two sides that determines whether the valve is blocked or open, regardless of the absolute pressure value. For example, if the pressure on the upstream (reservoir) side is already positive (e.g., 1.01 bar due to thermal expansion), but the pressure on the downstream (pump chamber) side is ambient pressure (1.0 bar, unactuated), then the pressure difference (here: 0.01 bar) is below a threshold (e.g., 20 mbar), which causes the valve to remain closed even when subjected to positive pressure in the opening direction. This means the check valve remains closed until the threshold pressure is reached, thereby keeping the passage between the reservoir and the pump chamber safely closed (e.g., when the suction device is not in use). Examples of threshold pressure differences are in the range of 1 mbar to 1000 mbar, more preferably between about 10 mbar and about 500 mbar, or between about 1 mbar and about 20 mbar.

[0060] When the suction device is actuated, energy is released as the device for storing potential energy changes its state from locked to unlocked. This causes the cylinder to perform its propulsive longitudinal movement, creating significant pressure in the pumping chamber. This generates a substantial pressure differential (due to the high pressure in the pumping chamber and the much lower pressure in the fluid reservoir) that exceeds a pressure differential threshold, causing the check valve to open and allowing the pressure chamber to fill with liquid from the reservoir.

[0061] One type of valve designed to operate under this threshold pressure difference is a spring-loaded ball valve. The spring pushes the ball into the valve seat, and the ball valve only opens when the pressure resisting the spring force exceeds the spring force. Other types of valves that can operate under this threshold pressure difference, depending on their construction, are duckbill valves or flap valves.

[0062] The advantage of this type of valve, which operates under a threshold pressure difference, is that the reservoir can remain closed until the suction device is actively used, thus reducing unnecessary splashing of reservoir liquid during device transport or evaporation during long-term storage of the device.

[0063] As described above, the pumping unit includes a riser having an upstream end and a downstream end, wherein the riser is adapted to function as a piston in the pumping unit. Furthermore, the pumping unit of the suction device of the present invention includes a retainer for holding the riser, the retainer being located downstream of the riser and securely attached to the user-facing side of the housing for fixation relative to the housing. According to the invention, the riser and retainer are in the form of a one-piece unit, or in other words, also in the form of an integral one-piece unit as described above, to produce a single structure including the riser and retainer such that the riser and retainer cannot be removed or detached from each other in a non-destructive manner, or in other words, the riser and retainer are arranged such that there is no intermediate phase between the riser and the corresponding retainer.

[0064] In some embodiments, the retainer and riser may comprise an injection-moldable polymer material, or in other words, be made of a material comprising an injection-moldable polymer material. The term "injection-moldable polymer material" as used herein is generally understood to mean any plastic polymer material that becomes flexible or moldable at a certain (elevated) temperature and solidifies upon cooling. In some embodiments, the retainer and riser comprise or are made of a material comprising at least one thermoplastic injection-moldable polymer material. In some embodiments, a one-piece unit comprising a retainer and riser may comprise different injection-moldable polymer materials, as further described below. However, in some embodiments, the retainer and riser may comprise the same injection-moldable polymer material.

[0065] In certain embodiments, risers and retainers in the form of one-piece units can be manufactured by injection molding at least one thermoplastic polymer material (e.g., by one-step injection molding of a selected thermoplastic polymer material).

[0066] In a particular embodiment, the one-piece unit including the riser and retainer may comprise a thermoplastic polymer material selected from the group consisting of: polyoxymethylene (POM; CAS No. 9002-81-7), polyetheretherketone (PEEK; CAS No. 29658-26-2), and poly(p-phenylene oxide) (PPO) (also known as poly(p-phenylene ether) (PPE; CAS No. 25134-01-4). In a further particular embodiment, the injection-moldable polymer material comprising the one-piece unit (including the riser and retainer) of the inhalation device and pumping unit of the present invention is polyetheretherketone (PEEK).

[0067] In a further embodiment, the injection-moldable polymer material included in the one-piece unit (including the riser and retainer) of the inhalation device of the present invention may be a mixture or blend, including at least one of PEEK, PPO / PPE and POM, and at least one other injection-moldable polymer material selected from the group consisting of: acrylonitrile butadiene styrene copolymer (ABS), acrylonitrile styrene acrylate (ASA), styrene acrylonitrile copolymer (SAN), polyacrylic acid (such as polymethyl methacrylate (PMMA)), acrylonitrile butadiene styrene copolymer (ABS), acrylonitrile butadiene styrene copolymer (ASA), polyacrylic acid (such as polymethyl methacrylate (PMMA)), acrylonitrile butadiene styrene copolymer (ASA), polyacrylic acid (such as polymethyl methacrylate (PMMA)), acrylonitrile butadiene styrene copolymer (ASA), polymethyl methacrylate (PMMA ... ABS), polyamide, polylactic acid (polylactide, PLA), polybenzimidazole (PBI), polycarbonate (PC), polyethersulfone (PES), polyoxymethylene (POM), polyetheretherketone (PEEK), polyetherimide (PEI), polyethylene (PE) (such as ultra-high molecular weight polyethylene (UHMWPE), high-density polyethylene (HDPE), medium-density polyethylene (MDPE), low-density polyethylene (LDPE)), polyphenylene ether (PPO), polyphenylene sulfide (PPS), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), polyvinylidene fluoride (PVDF), and polytetrafluoroethylene (PTFE).

[0068] In a further specific embodiment, the injection-moldable polymer material may be a mixture or blend, including polyetheretherketone (PEEK) and at least one of the following: polybenzimidazole (PBI, for example, poly[2,2'-( between [Phenylidene)-5,5'-dibenzimidazole; CAS No. 32075-68-6), polylactic acid (polylactide, PLA), and polyethersulfone (PESU / PES; CAS No. 25608-63-3). In a further specific embodiment, the injection-moldable material may be a mixture or blend comprising poly(terephthalamide) oxide (PPO / PPE) and polystyrene (thereby obtaining Noryl) TM (Commercially available materials). In yet another specific embodiment, the injection-molded material may be a mixture or blend of polyoxymethylene (POM) and polytetrafluoroethylene (PTFE).

[0069] In some embodiments, the one-piece unit (including riser and retainer) included in the inhalation device of the present invention may be substantially composed of an injection-molded material as described above, wherein the term “substantially composed of” as used herein means that the piston is composed of a selected thermoplastic polymer material in a weight ratio of at least 85% (relative to the total weight of the piston) or at least 90% or at least 95% or at least 97% or at least 98% or at least 99%.

[0070] In a further specific embodiment, the riser includes a fluid channel, which may be formed from an injection-molded material as described above.

[0071] In further embodiments, the one-piece unit including the riser and retainer may include a composite material comprising an injection-moldable material. In these embodiments, in addition to the injection-moldable material, the composite material may include a non-injection-moldable material. In some embodiments, the non-injection-moldable material included in the composite material may be at least one material selected from glass, metal, ceramic, 2 DPA-1 (e.g., in the form of fibers, beads, granules, or other suitable structures), or other solid materials (e.g., carbon fiber). In some embodiments, the non-injection-moldable material may be directly introduced into a selected injection-moldable material, and the resulting mixture may be injection-molded, for example, in the case of glass or carbon fiber. In alternative embodiments, the non-injection-moldable material may be introduced into a mold and overmolded by the injection-moldable material, a process also referred to by those skilled in the art as "insert molding."

[0072] In a further embodiment, only a portion of the one-piece unit, including the riser and retainer, may comprise or be substantially composed of the composite material described above, while other portions of the one-piece unit do not comprise non-injectable moldable materials. For example, the riser may not comprise non-injectable moldable materials and may be substantially composed of the thermoplastic injection-moldable material described above, while the retainer may comprise one or more non-injectable moldable materials described above. This may be particularly advantageous in embodiments where the riser and retainer have different dimensions and therefore different requirements (e.g., regarding mechanical stability).

[0073] In exemplary embodiments, the riser may be an elongated structure with an internal fluid channel and a circular cross-sectional diameter, while the corresponding retainer may be a mechanically more robust structure supporting the riser. For example, in these embodiments, the retainer may have a larger size, particularly a larger diameter, and may comprise a mechanically more robust material such as a composite material, while the riser may comprise or be substantially composed of a thermoplastic injection-molded material (such as PEEK, POM, or PPO / PPE). Thus, in some embodiments, the riser included in the one-piece unit may be substantially composed of an injection-molded material (such as PEEK, POM, or PPO / PPE), and the retainer may comprise the same injection-molded material, and in addition, further comprise injection-molded or non-injection-molded materials, such as materials in the form of the aforementioned composite materials. The retainer, or in other words, the retainer section (or in other words, the retainer section and the riser section) of the one-piece unit comprising the retainer and the riser can have all suitable sizes and cross-sectional shapes, for example, it can be in the form of a cylinder having a circular, elliptical, square, star-shaped or other cross-sectional shape, as long as these shapes and sizes are suitable for attaching the one-piece unit comprising the riser and the retainer to the housing in a mechanically stable manner.

[0074] As a further advantage, in these embodiments, the retainer may further include additional functional elements, such as a filter structure located downstream of the riser (and fluidly connected to the riser), or even a cascaded structure of multiple (continuous) filters. This also makes the design of the riser and corresponding retainer advantageous, eliminating the need for a separate additional retaining structure for such filter structures.

[0075] As described above, the riser includes a fluid channel, which can be formed from the injection-molded material described above. In some embodiments, the fluid channel fluidly connects an upstream end of the riser to a downstream end of the riser for delivering a medically active fluid. In some embodiments, the diameter of the fluid channel, preferably a constant diameter, can be selected from a range of up to about 5 mm, or up to about 4 mm, or up to about 3 mm, or up to about 2 mm, or selected from a range of about 0.05 mm to about 5 mm, or selected from a range of about 0.1 mm to about 4 mm, or about 3 mm, or about 2 mm, or selected from a range of about 0.1 mm to about 1 mm, or selected from a range of about 0.2 mm to about 0.8 mm, or selected from a range of about 0.03 mm to about 0.7 mm, or selected from a range of about 0.4 mm to about 0.6 mm, for example, 0.5 mm. In another embodiment, the (outer) diameter of the riser (perpendicular to the main axis connecting the upstream end and the downstream end of the riser) can be selected in the range of about 1 mm to about 10 mm, or about 7.5 mm, or about 5 mm, or about 3 mm, or about 2 mm, or in the range of about 1.5 mm to about 2 mm, for example, 1.5 mm or 1.8 mm.

[0076] In another embodiment, the length of the riser can be selected in the range of about 10 mm to about 30 mm, about 15 mm to about 25 mm, or about 20 mm, for example, about 17 mm.

[0077] In addition, the riser may include a coating, such as a polytetrafluoroethylene (PTFE) coating, applied to the outer surface of the piston. However, in some embodiments, the piston does not include a surface coating.

[0078] In some embodiments, the hollow cylinder included in the pumping unit of the inhalation device of the present invention may include or be substantially composed of a metal or polymer material selected from the group consisting of: acrylonitrile butadiene styrene copolymer (ABS), acrylonitrile styrene acrylate (ASA), styrene acrylonitrile copolymer (SAN), acrylonitrile butadiene styrene copolymer (ABS), polyamide, polylactic acid (polylactide, PLA), polybenzimidazole (PBI), polycarbonate (PC), polyethersulfone (PES), polyoxymethylene (POM), polyether ether ketone (PEEK), and polyphenylene ether (PPO).

[0079] In certain embodiments, the pump barrel comprises or is substantially composed of a thermoplastic polymer material selected from polyoxymethylene (POM; CAS No. 9002-81-7), polyetheretherketone (PEEK; CAS No. 29658-26-2), and poly(p-phenylene oxide) (PPO) (also known as poly(p-phenylene ether) (PPE; CAS No. 25134-01-4). In other embodiments, the pump barrel comprises or is substantially composed of PEEK, either as a composite material or as a non-composite material, i.e., excluding any non-injection moldable materials.

[0080] In a further embodiment, the pump barrel may comprise a thermoplastic polymer material in the form of a composite material, as described above in conjunction with a one-piece unit comprising a riser and a corresponding retainer.

[0081] A surprising finding is that, despite the considerable physical and mechanical stresses acting on the riser and retainer during operation of the pumping unit due to fluid pressures reaching approximately 100 bar or even higher, the riser and retainer of the pumping unit of the inhalation device of the present invention can still be fabricated as a one-piece unit, preferably a one-piece unit made of an injection-moldable material. Furthermore, a surprising finding is that a riser comprising, or even substantially comprising, an injection-moldable material can meet the high physical and mechanical requirements that a riser, as a piston in a medical high-pressure pumping unit, must meet, such as mechanical and chemical stability, surface properties (e.g., roughness), dimensional accuracy, temperature and pressure intolerance, chemical neutrality and tolerance, and hardness. This is particularly surprising given that the riser included in the one-piece unit (including the retainer) is hollow, thus including a fluid channel extending along the main axis of the riser. Despite the high physical and mechanical requirements and the fine structure of the riser (e.g., internal fluid channels), it is surprising to find that the riser can be manufactured by injection molding of materials, in the form of a one-piece unit including a retainer, the aforementioned materials including injection-moldable polymer materials. However, this can be considered a significant advantage when compared to current riser structures made of metals such as stainless steel, which must be reliably attached to the support and retaining structure in a separate manufacturing step. Furthermore, the one-piece riser and corresponding retainer design of this invention allows the riser to be positioned as close as possible to all functional structures located downstream of the riser (e.g., optional pre-filters and filters and / or nozzles), thereby avoiding any hollow spaces or dead zones formed before these structures.

[0082] Regarding the surface characteristics of the riser and retainer (e.g., riser section and retainer section of the retainer), the surface may have at least partially or entirely an average surface roughness (RA) between 0.010 μm and 0.060 μm, between 0.010 μm and 0.030 μm, preferably between 0.012 μm and 0.025 μm, or between 0.025 μm and 0.050 μm. In one aspect of this disclosure, the riser and retainer comprise a composite material, and the surface may have a molded surface finish according to the SPI A2 standard. In particular, it is advantageous for the riser and retainer to have these surface characteristics at the joints with other structures. For example, as described above, at the joint between the riser and retainer and the nozzle, these surface characteristics ensure a favorable interaction between the surface and, for example, a seal (such as an O-ring), which can ensure a proper seal between the nozzle and the riser and retainer.

[0083] The inventors discovered further advantages of using injectable materials. A surprising discovery was that pistons made from injectable materials are suitable for high-pressure medical pumping devices (such as the inhalation device according to the invention).

[0084] Therefore, in one aspect, the present invention relates to a high-pressure medical pumping device for providing discrete portions of a pressurized medical fluid, wherein the pumping device comprises: -Fluid inlet; - Fluid outlet; and - A pumping unit fluidly connected to a fluid inlet and a fluid outlet, and adapted to produce a discrete portion of a pressurized medical fluid, and adapted to deliver the discrete portion of the medically active fluid (downstream) from the fluid inlet to the fluid outlet; The pumping unit includes: - A pump casing, comprising a pump chamber located within the pump casing, the pump chamber including a fluid opening; and - A piston, comprising a first end and a second end opposite the first end, wherein the piston is at least partially located within a pump chamber of a pump barrel, such that at least the first end of the piston is located within the pump chamber, and wherein the piston and the pump barrel are arranged such that at least one of the piston and the pump chamber reciprocates relative to each other during a stroke. The piston includes a fluid passage fluidly connecting a first end of the piston to a second end of the piston, and is adapted to deliver medical fluid from either the first or second end of the piston to a corresponding opposite end of the piston; and The pumping unit is adapted to deliver discrete portions of pressurized medical fluid at a pressure of at least 100 bar; and The piston is made of an injection-moldable polymer material.

[0085] In a particular embodiment, the present invention relates to a handheld inhalation device for delivering medically active fluids, comprising a high-pressure medical pump as defined above.

[0086] The material of the piston can be as specified above.

[0087] In a further embodiment, the suction device of the present invention may further include an outlet valve located inside the riser or at the end of the riser to prevent liquid or air from flowing back from the riser into the hollow cylinder. In many cases, the use of such an outlet valve will prove advantageous. Typically, the downstream end of the riser is located near the nozzle. The nozzle is in fluid communication with the outside air. After a certain amount of liquid, supplied from the pumping unit through the nozzle, is atomized and sprayed, driven by the propulsive longitudinal movement of the cylinder, the pumping chamber must be refilled. For this purpose, the cylinder slides back to its previous upstream position on the riser (i.e., performing a repulsive longitudinal movement), increasing the internal volume of the pumping chamber. Simultaneously, a negative pressure (sometimes referred to as "underpressure") is generated inside the pumping chamber, causing liquid to be drawn into the pumping chamber from the fluid reservoir located upstream of the pumping chamber. However, this negative pressure can also be transmitted downstream through the riser to the outside of the nozzle, thus potentially causing 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 known as an outlet check valve) that opens toward the nozzle opening and blocks in the opposite direction.

[0088] Alternatively, the outlet valve can be of the type that blocks when the pressure difference is below a threshold (and opens when it is above a threshold), as described above in the context of the inlet valve. If a spring-loaded ball valve is used, the spring force must be aligned with the pumping chamber so that the outlet valve opens when the difference between the internal pressure of the pumping chamber and the ambient pressure exceeds the threshold pressure difference. The advantages of this type of valve correspond to the aforementioned advantages.

[0089] As described above, the outlet valve can be located within the riser. Alternatively, the suction device may include an outlet valve that is not integrated into the riser but is located at or near one end of the riser, particularly at or near its downstream end, for example, within a retainer located downstream of the riser as described above for holding the riser in place. This embodiment may be advantageous in certain situations, such as when a riser with a particularly small diameter is required, making valve integration difficult. By housing the outlet valve downstream of the riser, a relatively large-diameter valve can be used, thus simplifying the requirements for valve design.

[0090] In alternative embodiments, an outlet valve may be absent. These embodiments may be feasible because the fluid passage of an impingement nozzle can have a relatively small cross-section, resulting in only small or very slow backflow during device startup under given pressure conditions. If the backflow rate is considered acceptable for a particular product application, the inhaler design can be simplified by avoiding an outlet valve.

[0091] In any case, regardless of whether the inhalation device is designed with an outlet valve, all other choices and preferences regarding the description of other device features apply to these two alternative embodiments.

[0092] In a further embodiment, the inhalation device of the present invention may include a fluid reservoir securely attached to the hollow cylinder so that it can move within the housing together with the hollow cylinder. This means that during each injection phase of the pumping cycle, the fluid reservoir moves together with the hollow cylinder from an initial (“upstream”) position toward a final (“downstream”) position, where the pumping chamber has its maximum internal volume and at the final (“downstream”) position its minimum volume; and in a subsequent “start-up” step, the fluid reservoir returns together with the hollow cylinder to its initial (“upstream”) position.

[0093] As used herein, the expression "firmly attached" encompasses both permanent and non-permanent (i.e., releasable) forms of attachment. Furthermore, this expression includes both direct and indirect (i.e., via one or more connectors) types of attachment. Also, as stated above, "firmly attached" means that the corresponding parts are fixed to each other in a manner that substantially prevents them from moving relative to each other. In other words, two parts firmly attached to each other can only move together, while relative to each other, they are immovable or fixed in place.

[0094] One advantage of this embodiment, where the fluid reservoir is securely attached to the hollow cylinder, is that it minimizes the dead zone volume between the reservoir and the pumping chamber.

[0095] According to an alternative embodiment, the fluid reservoir can be fluidly connected to the hollow cylinder by means of a flexible tubular element and can be securely attached to the housing. According to this embodiment, when the cylinder performs its longitudinal movement, the reservoir is not securely attached to the hollow cylinder and therefore does not move with it. Instead, the reservoir is securely (but optionally removably) attached to the housing or a portion of the housing, directly or indirectly. One advantage of this embodiment is that the energy suddenly released when the device for storing potential energy is unlocked acts only on the hollow cylinder and not on the fluid reservoir. This may be particularly advantageous when the fluid reservoir has a relatively large mass when it is initially in its initial state (fully filled) and decreases during use. The higher acceleration of the hollow cylinder will translate into higher pressure in the pumping chamber.

[0096] To avoid ambiguity, all other choices and preferences regarding other device features described above and below apply to both alternatives, regardless of whether the fluid reservoir is securely attached to the hollow cylinder.

[0097] In some embodiments, the fluid reservoir is designed to be collapsible, such as by means of flexible or elastic walls. The effect of this design is that, during repeated use of the device involving the gradual emptying of the reservoir, the flexible or elastic walls bend or fold 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 require a significant increase. In particular, the reservoir can be designed as a collapsible bag. The advantage of a collapsible bag is that the pressure within the reservoir is almost independent of the filling level, and the effects of thermal expansion are negligible. Furthermore, this type of reservoir is relatively simple to construct and is well-established.

[0098] A similar effect can be achieved using a rigid container with a movable bottom (or walls), by which the internal volume of the reservoir can be continuously reduced.

[0099] In a second aspect, the present invention provides a one-piece unit comprising a riser and a retainer, which is adapted to be included in an inhalation device according to a first aspect of the invention. The one-piece unit according to this aspect of the invention is adapted to be included in an inhalation device according to a first aspect of the invention, and more specifically, is adapted (as a piston) to be included in a pumping unit of an inhalation device according to a first aspect of the invention.

[0100] To avoid ambiguity, it should be noted that all embodiments, features, definitions, descriptions, and combinations thereof disclosed in connection with the first aspect of the pumping apparatus of the present invention are equally applicable to this second aspect of the invention and all other aspects of the invention, although they are not repeated in connection with the present and all other aspects of the invention.

[0101] In a third aspect, the present invention provides a method for manufacturing a one-piece unit comprising a riser and a corresponding retainer according to a second aspect of the invention, wherein the method comprises injection molding of an injection-moldable material. In this context, it should be noted that general techniques for injection molding of injection-moldable polymeric materials (optionally in the form of composite materials) are known to those skilled in the art and are well documented in relevant standard literature, for example see Plastics Technology Handbook, M. Chanda, CRC Press, Nov. 2017, ISBN 9781498786218.

[0102] In a fourth aspect, the present invention provides a method for generating a nebulized aerosol of a medically active liquid. This method may involve using, in any embodiment thereof, an inhalation device as described above according to the first aspect of the invention. Therefore, all the choices and preferences above regarding the features of the inhalation device are equally applicable to the method provided according to the invention.

[0103] Specifically, the method includes the following steps: (a) A handheld inhalation device according to a first aspect of the invention is provided, wherein the fluid reservoir of the inhalation device comprises a medically active liquid, and wherein the means for storing potential energy is in an unlocked state; (b) The inhalation device is activated by changing its state from an unlocked state to a locked state using a device for storing potential energy, thereby causing the hollow cylinder to perform a repulsive longitudinal movement on the riser toward the upstream end of the pumping unit, so that the medically active liquid flows from the fluid reservoir into the hollow cylinder; and subsequently (c) The inhalation device is actuated by unlocking it using a device for storing potential energy, thereby achieving a propulsive longitudinal movement of the cylinder toward the downstream end of the pumping unit, and the medical active liquid is sprayed from the hollow cylinder in the downstream direction through a nozzle.

[0104] According to the present invention, during the movement of the hollow cylinder relative to the housing and nozzle, the riser remains stationary, while the cylinder providing the pumping chamber changes its relative position. In other words, the pumping chamber is movably supported within the housing, while the riser and nozzle are securely and permanently or statically attached to the housing and / or nozzle via retainers.

[0105] This method improves upon known methods in the prior art by relying on the use of a particularly advantageous inhalation device, wherein the component corresponding to the riser (i.e., the hollow piston) is movable relative to the housing and the nozzle, while the riser is stationary.

[0106] According to a further embodiment, the described method can be performed by means of an inhalation device that provides one, several, or all of the foregoing features, such as: a reservoir securely attached to a hollow cylinder or a housing, and optionally configured as a collapsible bag; an inlet check valve, optionally operable by using a threshold pressure differential; a device for storing potential energy, such as a spring; a locking device; and an outlet valve, for example, disposed inside the riser or between the riser and the nozzle. For an explanation of the corresponding operation of the features, refer to the sections of the specification relating to the corresponding device features.

[0107] According to a further specific and advantageous embodiment, the present invention provides a method for generating an aerosol of a medically active liquid by means of an inhalation device, the device comprising a housing, a pumping device having a pumping chamber, a riser integrally formed with a retainer, and a nozzle, the method being accomplished by performing the following steps: - The inner end of the riser is moved into the inner volume of the pumping chamber, thereby reducing the inner volume of the pumping chamber and increasing the pressure of the liquid contained within that volume; and - The liquid is sprayed through the outer end of the riser and the nozzle to form a spray; The method described above is characterized in that, during the movement, the riser remains stationary relative to the housing and / or nozzle, while the pumping chamber changes its relative position.

[0108] As shown above, the present invention overcomes the shortcomings of known technologies, particularly those related to manufacturing costs and the number of process steps. The present invention also enables the atomization and delivery of higher viscosity liquids into aerosols with high reproducibility and in a short time.

[0109] The following is a list of embodiments numbered E1 to E32 included in this invention: E1. A handheld inhalation device for delivering a nebulized medical active fluid (F) for inhalation therapy, comprising: (a) A housing (1) having a side facing the user; (b) A nozzle (6) for generating an atomized aerosol by the collision of at least two liquid jets, the nozzle (6) being securely attached to the user-facing side of the housing (1) so as to be fixed relative to the housing (1); (c) A fluid reservoir (2) disposed within the housing (1) for containing the medically active fluid; and (d) A pumping unit, arranged within the housing (1), the pumping unit having: -The upstream end, which is fluidly connected to the fluid reservoir (2); and -The downstream end is fluidly connected to the nozzle (6). The pumping unit is adapted to pump the medical active fluid (F) from the fluid reservoir (2) to the nozzle (6). The pumping unit further includes: (i) A riser (5) having an upstream end and a downstream end, wherein the riser (5) is adapted to serve as a piston in the pumping unit; (ii) A retainer (10) located downstream of the riser and securely attached to the user-facing side of the housing (1) to be fixed relative to the housing (1) for retaining the riser; (iii) A hollow cylinder (9) located upstream of the riser (5), wherein the upstream end of the riser (5) is inserted into the cylinder (9) such that the cylinder (9) is longitudinally movable on the riser (5); and (iv) A lockable device (7) for storing potential energy, which stores potential energy when locked and releases the stored energy when unlocked, the device (7) being disposed outside the cylinder (9) and mechanically coupled to the cylinder (9) such that the device (7) is unlocked so that the cylinder (9) can be pushed longitudinally toward the downstream end of the pumping unit. The retainer (10) and the riser (5) are one-piece units.

[0110] E2. The inhalation device according to claim 1, wherein the retainer (10) and the riser (5) comprise an injection-moldable polymer material.

[0111] E3. The inhalation device according to embodiment E1 or E2, wherein the retainer (10) and the riser (5) are made of a material comprising at least one thermoplastic injection-molded polymer material.

[0112] E4. The inhalation device according to any of the foregoing embodiments, wherein the retainer (10) and the riser (5) comprise the same injection-moldable polymer material.

[0113] E5. The inhalation device according to any of the foregoing embodiments, wherein the riser (5) and the retainer (10) in the form of a one-piece unit are manufactured by injection molding at least one thermoplastic polymer material.

[0114] E6. The inhalation device according to any of the foregoing embodiments, wherein the injection-moldable polymer material is selected from the group consisting of: polyoxymethylene (POM), polyetheretherketone (PEEK), and polyphenylene ether (PPO / PPE).

[0115] E7. The inhalation device according to any of the foregoing embodiments, wherein the injection-moldable polymer material is a mixture or blend comprising at least one injection-moldable material and at least one additional injection-moldable polymer material, wherein the at least one injection-moldable material is selected from the group consisting of PEEK, PPO / PPE, and POM, and the at least one additional injection-moldable polymer material is selected from the group consisting of: acrylonitrile butadiene styrene copolymer (ABS), acrylonitrile styrene acrylate (ASA), styrene acrylonitrile copolymer (SAN), polyacrylic acid (such as polymethyl methacrylate (PMMA)), acrylonitrile butadiene... Styrene copolymer (ABS), polyamide, polylactic acid (polylactide, PLA), polybenzimidazole (PBI), polycarbonate (PC), polyethersulfone (PES), polyoxymethylene (POM), polyetheretherketone (PEEK), polyetherimide (PEI), polyethylene (PE) (such as ultra-high molecular weight polyethylene (UHMWPE), high-density polyethylene (HDPE), medium-density polyethylene (MDPE), low-density polyethylene (LDPE)), polyphenylene ether (PPO), polyphenylene sulfide (PPS), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), polyvinylidene fluoride (PVDF), and polytetrafluoroethylene (PTFE).

[0116] E8. The inhalation device according to any of the foregoing embodiments, wherein the at least one injectable material is polyetheretherketone (PEEK).

[0117] E9. The inhalation device according to any of the foregoing embodiments, wherein the piston comprises a composite material, the composite material comprising an injection-moldable material.

[0118] E10. The inhalation device according to embodiment E9, wherein, in addition to the injectable material, the composite material also includes a non-injectable material.

[0119] E11. The inhalation device according to embodiment E9 or E10, wherein the composite material comprises at least one non-injectable material selected from glass, metal, ceramic, 2 DPA-1 (e.g., in the form of fibers, beads, granules or other suitable structures) or other solid materials such as carbon fiber.

[0120] E12. The inhalation device according to any of the foregoing embodiments, wherein the riser is substantially composed of the injection-molded material.

[0121] E13. The inhalation device according to any one of the preceding claims, wherein the fluid passage (11) of the riser is formed of an injection-molded material.

[0122] E14. The inhalation device according to any of the foregoing embodiments, wherein the hollow cylinder comprises metal or polymer materials such as acrylonitrile butadiene styrene copolymer (ABS), acrylonitrile styrene acrylate (ASA), styrene acrylonitrile copolymer (SAN), acrylonitrile butadiene styrene copolymer (ABS), polyamide, polylactic acid (polylactide, PLA), polybenzimidazole (PBI), polycarbonate (PC), polyethersulfone (PES), polyoxymethylene (POM), polyether ether ketone (PEEK), and polyphenylene ether (PPO).

[0123] E15. An inhalation device according to any of the foregoing embodiments, wherein the riser includes a fluid channel fluidly connecting an upstream end of the riser to a downstream end of the riser for delivering the medically active fluid.

[0124] E16. The inhalation device according to embodiment E15, wherein the diameter of the fluid channel is selected in the range of about 0.1 mm to about 1 mm.

[0125] E17. The inhalation device according to any of the foregoing embodiments, wherein the diameter of the riser (perpendicular to the main axis connecting the upstream end and the downstream end of the riser) is selected in the range of about 1 mm to about 3 mm.

[0126] E18. An inhalation device according to any of the foregoing embodiments, wherein the retainer further includes a filter structure located downstream of the riser (and fluidly connected to the riser).

[0127] E19. The inhalation device according to embodiment E18, wherein the filter structure comprises a cascaded structure of a plurality of (continuous) filters.

[0128] E20. The inhalation device according to any of the foregoing embodiments, wherein the nozzle includes an impact nozzle.

[0129] E21. The inhalation device according to any of the foregoing embodiments, wherein the pumping unit further includes a locking member for locking the lockable device.

[0130] E22. The inhalation device according to any of the foregoing embodiments, wherein the pumping unit is a high-pressure pumping unit adapted to discharge fluid (F) at a pressure of at least 50 bar.

[0131] E23. The inhalation device according to any of the foregoing embodiments, wherein the device (7) for storing potential energy is a spring having a load of at least 10N in the deflected state.

[0132] E24. An inhalation device according to any of the foregoing embodiments, the inhalation device being adapted to deliver atomized medical active aerosol in discrete units, wherein one unit is delivered per pumping cycle.

[0133] E25. The inhalation device according to Example E24, wherein a unit aerosol contains 2µL to 150µL of liquid phase.

[0134] E26. The inhalation device according to any of the foregoing embodiments, wherein the pumping unit further includes an inlet valve (4) located downstream or at the downstream end of the hollow cylinder (9).

[0135] E27. The inhalation device according to embodiment E26, wherein the inlet valve (4) is adapted to open only when the pressure difference between the upstream and downstream sides of the inlet valve (4) is higher than a predetermined threshold, and wherein the predetermined threshold is in the range of 1 mbar to 20 mbar.

[0136] E28. The inhalation device according to any of the foregoing embodiments further includes an outlet valve (8) inside the riser (5) to prevent liquid (F) or air from flowing back from the riser (5) into the hollow cylinder (9).

[0137] E29. An inhalation device according to any of the foregoing embodiments, wherein the fluid reservoir (2) is securely attached to the hollow cylinder (9) so that it can move together with the hollow cylinder (9) within the housing (1).

[0138] E30. An inhalation device according to any of the foregoing embodiments, wherein the fluid reservoir (2) is fluidly connected to the hollow cylinder (3) by means of a flexible tubular element and is securely attached to the housing (1).

[0139] E31. The inhalation device according to any of the foregoing embodiments, wherein the fluid reservoir (2) is designed as a collapsible bag.

[0140] E32. A method for generating a mist aerosol of a medically active liquid (F), comprising the following steps: - Provide a handheld inhalation device as defined in any of the foregoing embodiments, wherein the fluid reservoir (2) of the inhalation device comprises a medically active liquid (F), and wherein the device (7) for storing potential energy is in an unlocked state; - The inhalation device is activated by changing the state of the device (7) for storing potential energy from the unlocked state to the locked state, thereby causing the hollow cylinder (9) to perform a repulsive longitudinal movement on the riser (5) toward the upstream end of the pumping unit, so as to allow medically active liquid (F) to flow from the fluid reservoir (2) into the hollow cylinder (9); and subsequently - The inhalation device is actuated by unlocking the device (7) for storing potential energy, thereby enabling the cylinder (9) to move longitudinally toward the downstream end of the pumping unit, and the medical active liquid (F) is sprayed from the hollow cylinder (9) in the downstream direction through the nozzle (6).

[0141] In a particular embodiment, the present invention relates to the following further embodiments of a high-pressure medical pumping device comprising a piston made of an injection-molded material: A1. A high-pressure medical pumping device for providing discrete portions of a pressurized medical fluid, wherein the pumping device comprises: -Fluid inlet; - Fluid outlet; and - A pumping unit fluidly connected to the fluid inlet and the fluid outlet, adapted to generate a discrete portion of the medical fluid in pressurized form, and adapted to deliver the discrete portion of the medically active fluid (downstream) from the fluid inlet to the fluid outlet; The pumping unit includes: - A pump casing, comprising a pump chamber located within the pump casing, the pump chamber including a fluid opening; and A piston comprising a first end and a second end opposite the first end, wherein the piston is at least partially located within the pump chamber of the pump barrel, such that at least the first end of the piston is located within the pump chamber, and wherein the piston and the pump barrel are arranged such that at least one of the piston and the pump chamber reciprocates relative to each other during a stroke. The piston includes a fluid channel fluidly connecting a first end of the piston to a second end of the piston, and is adapted to deliver the medical fluid from either the first or second end of the piston to a corresponding opposite end of the piston; and The pumping unit is adapted to provide discrete portions of pressurized medical fluid at a pressure of at least about 100 bar; and The piston comprises an injection-moldable polymer material.

[0142] A2. The high-pressure medical pumping device according to embodiment A1, wherein the medical pumping unit is adapted to provide discrete portions of pressurized medical fluid at a pressure of at least about 150 bar, or at least about 175 bar, or at least about 200 bar.

[0143] A3. The high-pressure medical pumping device according to embodiment A1 or A2, wherein the medical pumping device includes a check valve fluidly connected to the fluid inlet and the pumping unit (and located between the fluid inlet and the pumping unit).

[0144] A4. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the pumping device is adapted to be included in a mobile inhalation device, preferably included in a handheld mobile inhalation device.

[0145] A5. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the pumping device is adapted to be included in an inhalation device for administering a medical fluid in the form of an atomized liquid for inhalation.

[0146] A6. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the liquid inlet is fluidly connected to a reservoir for containing the medical fluid, such as a reservoir in the form of a dimensionally stable or flexible container.

[0147] A7. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the fluid outlet is fluidly connected to a nozzle for discharging and optionally atomizing the pressurized medical fluid being delivered, such as an impact nozzle for atomizing the medical fluid by colliding at least two liquid jets of the medical fluid.

[0148] A8. A high-pressure medical pumping device according to any of the foregoing embodiments, wherein the fluid opening of the pump barrel is fluidly connected to the fluid inlet of the pumping device (and optionally to the reservoir) and is located downstream of the fluid inlet of the pumping device, and wherein the second end of the piston is fluidly connected to the fluid outlet of the pumping device.

[0149] A9. The high-pressure medical pumping device according to embodiment A8, wherein the pumping unit includes a check valve, and wherein the check valve includes a fluid inlet in the pump barrel and / or positioned adjacent to the pump barrel.

[0150] A10. The high-pressure medical pumping device according to embodiment A8 or A9, wherein the piston is arranged in a fixed position within the pumping unit such that the piston remains stationary during the reciprocating stroke of the pump chamber.

[0151] A11. A high-pressure medical pumping device according to any one of embodiments A1 to A8, wherein the fluid opening of the pump barrel is fluidly connected to the fluid outlet of the pumping device and is located upstream of the fluid outlet of the pumping device, and wherein the second end of the piston is connected to the fluid inlet of the pumping device.

[0152] A12. The high-pressure medical pumping device according to embodiment A11, wherein the pumping unit includes a check valve, the check valve being included in the piston and optionally positioned at a first end of the piston.

[0153] A13. The high-pressure medical pumping device according to embodiment A11 or A12, wherein the pump barrel is arranged in a fixed position within the pumping unit such that the pump barrel remains stationary during the reciprocating stroke of the piston.

[0154] A14. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein a discrete portion of the pressurized medical fluid is generated by a stroke motion of at least one of the piston and the pump barrel.

[0155] A15. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the injection-molded material is a thermoplastic polymer material.

[0156] A16. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the injection-moldable polymer material is selected from the group consisting of polyoxymethylene (POM), polyetheretherketone (PEEK), and polyphenylene oxide (PPO / PPE).

[0157] A17. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the injection-moldable polymer material is a mixture or blend comprising at least one injection-moldable material and at least one other injection-moldable polymer material, wherein the at least one injection-moldable material is selected from the group consisting of PEEK, PPO / PPE, and POM, and the at least one other injection-moldable polymer material is selected from the group consisting of: polyacrylic acid (such as polymethyl methacrylate (PMMA)), acrylonitrile butadiene styrene copolymer (ABS), polyamide, polyemulsion... Acids (polylactide, PLA), polybenzimidazole (PBI), polyethersulfone (PES), polyoxymethylene (POM), polyetheretherketone (PEEK), polyetherimide (PEI), polyethylene (PE) (such as ultra-high molecular weight polyethylene (UHMWPE), high-density polyethylene (HDPE), medium-density polyethylene (MDPE), low-density polyethylene (LDPE)), polyphenylene ether (PPO), polyphenylene sulfide (PPS), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), polyvinylidene fluoride (PVDF), and polytetrafluoroethylene (PTFE).

[0158] A18. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the at least one injection-molded material is polyetheretherketone (PEEK).

[0159] A19. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the piston comprises a composite material, and the composite material comprises an injection-moldable material.

[0160] A20. The high-pressure medical pumping device according to embodiment A19, wherein, in addition to the injectable material, the composite material also includes a non-injectable material.

[0161] A21. The high-pressure medical pumping device according to embodiment A19 or A20, wherein the composite material comprises at least one non-injectable molding material selected from glass, metal, ceramic, 2 DPA-1 (e.g., in the form of fibers, beads, granules or other suitable structures) or other solid materials such as carbon fiber.

[0162] A22. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the piston is substantially composed of the injection-molded material.

[0163] A23. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the fluid channel of the piston is formed of an injection-molded material.

[0164] A24. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the pumping unit of the high-pressure medical pumping device of the present invention includes a pump barrel that may comprise or is substantially composed of a metal or polymer material, the polymer material being selected from the group consisting of: acrylonitrile butadiene styrene copolymer (ABS), acrylonitrile styrene acrylate (ASA), styrene acrylonitrile copolymer (SAN), acrylonitrile butadiene styrene copolymer (ABS), polyamide, polylactic acid (polylactide, PLA), polybenzimidazole (PBI), polycarbonate (PC), polyethersulfone (PES), polyoxymethylene (POM), polyether ether ketone (PEEK), and polyphenylene ether (PPO).

[0165] A25. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the main axis of the fluid channel is connected to the center of the first end and the second end of the piston, and wherein the diameter of the fluid channel is perpendicular to the main axis, the diameter being selected in the range of about 0.1 mm to about 1 mm, preferably in the range of about 0.3 mm to about 0.7 µm.

[0166] A26. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the outer diameter of the piston (perpendicular to the main axis) is selected in the range of about 1 mm to about 10 mm, preferably in the range of about 1 mm to about 3 mm.

[0167] A27. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the volume of the pump chamber (defined by the inner wall of the pump barrel and the first end of the piston) is in the range of about 1µL to about 100µL, preferably selected in the range of about 15µL to about 30µL.

[0168] A28. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the pumping unit includes a drive unit adapted to drive the stroke movement of at least one of the piston and the pump barrel.

[0169] A29. The high-pressure medical pumping device according to embodiment A28, wherein the drive unit is adapted to apply a driving force to at least one of the piston and the pump barrel in the range of about 35 N to about 80 N.

[0170] A30. A high-pressure medical pumping device according to any of the foregoing embodiments, wherein the pumping unit includes a lockable device for storing potential energy, which stores potential energy when locked and releases the stored energy when unlocked, the device being disposed outside and mechanically coupled to at least one of the pump barrel and the piston, such that the device is unlocked to allow at least one of the pump barrel and the piston to propel longitudinally toward the corresponding other of the pump barrel and the piston.

[0171] A31. The high-pressure medical pumping device according to embodiment A30, wherein the device for storing potential energy includes a spring, for example a spring having a load of at least 35N in a deflected state.

[0172] A32. The high-pressure medical pumping device according to embodiment A30 or A31, wherein the pumping unit further includes a locking member for locking the lockable device.

[0173] A33. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein each pumping cycle delivers a discrete portion of the medical fluid.

[0174] A34. The high-pressure medical pumping unit according to any of the foregoing embodiments, wherein the volume of a discrete portion of the medical fluid is selected in the range of 2µL to about 150µL.

[0175] A35. The high-pressure medical pumping device according to any of the foregoing embodiments, wherein the medical fluid is a liquid composition comprising an aqueous or alcoholic liquid carrier and optionally at least one medically active ingredient and optionally at least one pharmaceutically acceptable excipient.

[0176] A36. An inhalation device for administering a medical liquid in the form of an atomized liquid, the inhalation device comprising a high-pressure medical pump according to any one of embodiments A1 to A35.

[0177] A37. A piston for use in the pumping unit of a high-pressure medical pumping apparatus according to any one of embodiments A1 to A36.

[0178] A38. A method for manufacturing a piston according to embodiment A37, wherein the method comprises injection molding of an injection-moldable material.

[0179] Detailed description of the attached diagram Figure 1A schematic, but not to scale, illustration of an inhalation device according to the invention is shown. In the illustrated device, a riser (5) is attached to a housing (1) via a retainer (10), wherein the riser (5) and the retainer (10) are in the form of a single unit. Figure 1 The image shows the condition before the first use.

[0180] The inhalation device includes a housing (1) preferably shaped and sized to be held in one hand and operated with a single finger (e.g., thumb or forefinger (not shown)). A fluid reservoir (2) for storing a medically active liquid (F) is located inside the housing (1). The depicted reservoir (2) is designed to be collapsible, such that during repeated use of the device and emptying of the reservoir, the flexible or elastic walls deform, so that the negative pressure required to draw liquid from the reservoir remains substantially constant over time. A similar effect can be achieved using a rigid container with a movable bottom, by which the internal volume of the reservoir can also be continuously reduced (not shown).

[0181] Furthermore, the inhalation device includes a pumping unit having a hollow cylinder (9) within the housing (1), which forms a pumping chamber (3) for generating the desired pressure necessary for the jet liquid (F) and the atomized liquid. The pumping unit may also include other components not shown in the figure, such as buttons, locking devices, etc.

[0182] A spring is provided as a device (7) for storing potential energy. The spring is connected to the cylinder (9) through one end (the upward or downstream end) and supported on the housing (1) (the lower part in the figure).

[0183] The suction device further includes a riser (5) having at least one internal end (5A) facing the reservoir or upstream, which can be accommodated in the aforementioned cylinder (9). In other words, the riser (5) can be at least partially pushed into the hollow cylinder (9), resulting in a reduction in the internal volume of the pumping chamber (3). The term "internal volume" describes the volume of the space extending from the inlet of the cylinder (9) facing the reservoir to the location of the internal end (5A) of the riser (5). In the depicted case, the riser (5) is almost completely contained within the cylinder (9). Therefore, the internal volume of the pumping chamber (3) located between the inlet valve (4) and the internal end (5A) of the riser (5) is minimized.

[0184] Preferably, the hollow cylinder (9) section (or segment) that serves as or houses the pumping chamber (3) and houses the riser (5) has a circular inner cross-section whose diameter is relatively close (e.g., except for small gaps) to match the diameter of the circular outer cross-section of the corresponding segment of the riser (5). Of course, other (e.g., non-circular) cross-sectional shapes are also feasible.

[0185] According to the described embodiment, the inlet valve (4) is arranged between the reservoir (2) and the inlet of the pumping chamber (3) formed by the cylinder (9).

[0186] Furthermore, the inhalation device includes a nozzle (6) that is liquid-tightly connected to the outer (or downstream) end (5B) of the riser (5). The nozzle (6) is an impingement nozzle for generating an atomized aerosol through the collision of at least two liquid jets. Preferably, the cross-section of the liquid-containing channel is relatively small, typically in the micrometer range.

[0187] Similarly, an optional outlet valve (8) inside the riser (5) is depicted to prevent liquid or air from flowing back from the outside to the outer end (5B) of the riser. The outlet valve (8) is located in the inner end (5A) of the riser (5). Liquid (F) can pass through the outlet valve (8) in the direction of the nozzle (6), but the outlet valve (8) blocks unwanted backflow in the opposite direction.

[0188] from Figure 1 As can be seen, the riser (5) has a fluid passage (11) and is designed to be fixed relative to the housing (1), and is securely attached to the housing (1) via a retainer (10). The retainer (10), which is schematically shown here, can of course have any suitable size and cross-sectional shape, for example, it can be a cylinder with a circular, elliptical, square, star-shaped or other cross-sectional shape. The riser (5) (which is in the form of a one-piece unit with the retainer (10)) is also securely attached to the nozzle (6) via the retainer (10), which in turn is also attached to the housing (1). Conversely, the hollow cylinder (9) providing the pumping chamber (3) is designed to be movable relative to the housing (1) and the nozzle (6). The benefits of this design have been explained; refer to the corresponding section in the description above.

[0189] Reference Figure 2 Depicting with Figure 1 The device is similar to the one described above. However, Figure 2 The illustrated embodiment lacks an (optional) outlet valve (8). All other components are present and function similarly. In this embodiment, the pumping chamber (3) extends upward from downstream of the valve (4) to the nozzle (6), where fluid resistance increases significantly. In an alternative embodiment with a particularly small internal diameter of the riser (5), the pumping chamber (3) extends upward only from downstream of the valve (4) to the upstream internal end (5A) of the riser (5).

[0190] Figure 3 It shows Figure 1In this embodiment, the pumping chamber has been filled. The hollow cylinder (9) has been moved to its upstream position, thereby loading the device (7) for storing potential energy. The outlet valve (8) is closed due to the negative pressure inside the pumping chamber (3), and the inlet valve (4) is opened toward the fluid reservoir (2). The increasingly collapsing walls of the reservoir (2) keep the internal pressure inside the reservoir (2) almost constant, while the pressure inside the pumping chamber (3) decreases due to the propulsive longitudinal movement of the hollow cylinder (9), thus increasing the volume of the pumping chamber (3). Therefore, the pumping chamber (3) has been filled with liquid (F) from the reservoir (2).

[0191] exist Figure 4 In, it is shown Figure 1 The situation after the first actuation of the inhalation device. The device (7) for storing potential energy has been removed from... Figure 3 The loading position shown is released. The device (7) for storing potential energy pushes the cylinder (9) downstream so that it slides on the riser (5). The inner end (5A) of the riser (5) is closer to the inlet check valve (4), which is now closed. As a result, the pressure inside the pumping chamber (3) increases, keeping the inlet valve (4) closed, but opening the outlet valve (8). Liquid (F) flows from the riser (5) through its outer end (5B) to the nozzle (6).

[0192] Figure 5 It shows Figure 1 The device is in its final state at the end of the aerosol spraying phase. The device (7) for storing potential energy is in its most relaxed end position (spring fully extended). Furthermore, the hollow cylinder (9) has been almost completely pushed onto the riser (5), so that the internal volume of the pumping chamber (3) has reached its minimum. Most of the liquid (F) previously contained in the pumping chamber (3) has passed through the outlet valve (8) into the main section of the riser (5). Some of the liquid (F) is pushed toward and through the nozzle (6), where it is atomized, causing the atomized aerosol to be sprayed toward the user or patient.

[0193] exist Figure 6 In the middle, it is described Figure 1 The device after refilling the pumping chamber. The hollow cylinder (9) has moved upstream (repulsively), thus increasing the volume of the pumping chamber (3) supplied by the cylinder (9). The device (7) for storing potential energy has been loaded (spring compressed). As the cylinder (9) moves away from the nozzle (6), a negative pressure is generated in the pumping chamber (3), thereby closing the outlet valve (8) and opening the inlet check valve (4). Thus, more liquid (F) is drawn from the reservoir (2) into the pumping chamber (3). The pumping chamber (3) of the suction device is refilled and ready for the next injection of liquid (F) by releasing the spring.

[0194] Figure 7 Another embodiment of the inhalation device according to the invention is depicted, wherein... Figures 1 to 6 The structures in the embodiments are referred to by the same reference numerals. It can be seen that the riser (5) with the fluid channel (11) is also configured as a one-piece unit with the retainer (10). In this particular embodiment, the riser (5) and the retainer (11) in the form of a one-piece unit are made of polyetheretherketone (PEEK).

[0195] Figures 8 to 10 The illustration depicts a schematic, but not to scale, embodiment of the invention, in which a piston made of an injection-molded material is used to provide discrete portions of a pressurized medical fluid (F) in a high-pressure medical pumping device (101) of the invention. The pumping device (101) includes a fluid inlet (102), a fluid outlet (103), and a pumping unit (110) fluidly connecting the fluid inlet (102) and the fluid outlet (103). The pumping unit is adapted to produce discrete portions of the pressurized medical fluid (F) and to deliver discrete portions of the medically active fluid (F) downstream from the fluid inlet (102) to the fluid outlet (103). The pumping unit (110) includes a pump barrel (111) that includes a pump chamber (112) located within the pump barrel (111). The pump chamber (112) includes a fluid opening (113). The high-pressure medical pumping device (101) also includes a piston (120) having a first end (121) and a second end (122) opposite to the first end, wherein the piston (120) is at least partially located within the pump chamber (112) of the pump barrel (111), such that at least the first end (121) of the piston is located within the pump chamber (112). The piston (120) and the pump barrel (111) are arranged for at least one of the piston (120) and the pump chamber (112) to reciprocate relative to each other.

[0196] The piston (120) includes a fluid passage (123) fluidly connecting a first end (121) of the piston to a second end (122) of the piston, and is adapted to deliver medical fluid (F) from either the first end (121) or the second end (122) of the piston to the corresponding opposite end of the piston. Figures 8 to 10 In the illustrated embodiment, the pumping unit (110) of the high-pressure medical pumping device (101) further includes a check valve (104) located in the pump chamber near and downstream of a fluid opening (113) in the pump chamber. (As in conjunction with...) Figure 9 and Figure 10 And further detailed description below Figures 11 to 13 exist Figure 8As can be seen, the pumping unit (110) of the high-pressure medical pumping device of the present invention is adapted to provide discrete portions of a pressurized medical fluid (F) at a pressure of at least about 100 bar. According to the invention, the piston (120) comprises an injection-moldable polymer material.

[0197] exist Figures 8 to 10 In the illustrated embodiment, the fluid inlet (102) of the high-pressure medical pumping device may be connected to, for example, a reservoir (130, not shown), and the fluid outlet (103) may be connected to, for example, a nozzle (140, not shown). This enables the pumping of discrete portions of pressurized medical fluid (F) from the fluid inlet (102) in a downstream direction toward the fluid outlet (103).

[0198] Figure 8 The state of the high-pressure medical pumping device (101) at the start of a pumping cycle is depicted. In this case, the piston (120) is maximally introduced into the pump chamber (112) of the pump barrel (111), resulting in a minimum volume of the pump chamber (112).

[0199] Figure 9 Depicting and Figure 8 The same high-pressure medical pumping device (101) is depicted, but in a state or condition following a pumping cycle. Figure 9 This illustrates the high-pressure medical pumping device (101) after the piston (120) and / or the pump barrel move (repulsively) relative to each other, causing the piston (120) to move outward out of the pump barrel (111) (i.e., downstream). To avoid confusion, this repulsive relative movement can be achieved by the respective movement of the piston (120) alone or the pump barrel (111) alone, or by the respective simultaneous movement of the piston (120) and the pump barrel (111). Figure 9 As can be seen, through this relative repulsive movement, medical fluid (F) is delivered or pumped from the reservoir (130, not shown) to the pump chamber (112) via the fluid inlet (102), the fluid opening (113) of the pump barrel, and the check valve (104).

[0200] Figure 10 Depicting and Figure 8 and Figure 9 The same high-pressure medical pumping device (101) is depicted, but in a subsequent state or condition of the pumping cycle. Figure 10The diagram illustrates a high-pressure medical pumping device (101) after a propulsive relative movement of the piston (120) and / or the pump barrel (111) relative to each other results in the piston (120) moving inward back into the pump barrel (111) (i.e., in the upstream direction). To avoid ambiguity, this propulsive relative movement can be achieved by the respective movement of the piston (120) alone or the pump barrel (111) alone, or by the respective simultaneous movement of the piston (120) and the pump barrel (111). From Figure 10 As can be seen, through this relative propulsive movement, discrete portions of the medical fluid (F) are delivered or pumped from the pump chamber (112) via the fluid passage (123) of the piston toward the fluid outlet (103), which may, for example, be fluidly connected to a nozzle (140, not shown)). Thus (and after the ejection of discrete portions of the pressurized medical fluid (F), the high-pressure medical pumping device (101) is ready for the next pumping cycle.

[0201] Figures 11 to 13 An alternative embodiment of the high-pressure medical pumping device (101) of the present invention is shown, which is similar to... Figures 8 to 10 The difference in the embodiment is that the fluid inlet (102) (optionally fluidly connected to the reservoir (130, not shown)) is located near the second end (122) of the piston, and the fluid outlet (103) is located near the fluid opening (113) of the pump chamber (optionally fluidly connected to the nozzle (140, not shown).

[0202] Figure 11 This alternative embodiment of the high-pressure medical pumping device (101) is depicted at the beginning of a pumping cycle. In this case, the piston (120) is maximally introduced into the pump chamber (112) of the pump barrel (111), resulting in a minimum volume of the pump chamber (112). It should be noted that in this embodiment, the high-pressure medical pumping device (101) does not include a check valve; however, such a check valve may be implemented, for example, at the first end (121) or the second end (122) of the piston, or in the fluid passage (123) of the piston, or at the fluid inlet (102).

[0203] Figure 12 Depicting and Figure 11 The same high-pressure medical pumping device (101) is depicted, but in a state or condition following a pumping cycle. Figure 12 The diagram illustrates a high-pressure medical pumping device (101) after a (repulsive) movement of the piston (120) and / or the pump barrel relative to each other causes the piston (120) to move outward out of the pump barrel (i.e., in the upstream direction). To avoid ambiguity, this repulsive relative movement can be achieved by corresponding movement of the piston (120) alone or the pump barrel (111) alone, or by corresponding simultaneous movement of the piston (120) and the pump barrel (111). From Figure 12 As can be seen, through this relative repulsive movement, medical fluid (F) is delivered or drawn from the reservoir (130, not shown) into the pump chamber (112) via the fluid inlet (102) and the fluid passage (123) of the piston.

[0204] Figure 13 Depicting and Figure 11 and Figure 12 The same high-pressure medical pumping device (101) is depicted, but in a state or condition following a pumping cycle. Figure 13 The diagram illustrates a high-pressure medical pumping device (101) after a propulsive relative movement of the piston (120) and / or the pump barrel relative to each other causes the piston (120) to move inward back into the pump barrel (i.e., downstream). To avoid ambiguity, this propulsive relative movement can be achieved by corresponding movement of the piston (120) alone or the pump barrel (111) alone, or by corresponding simultaneous movement of the piston (120) and the pump barrel (111). Figure 13 As can be seen, through this relative propulsive movement, discrete portions of the medical fluid (F) are delivered or pumped from the pump chamber (112) via the fluid opening (113) of the pump barrel toward the fluid outlet (103), which may, for example, be fluidly connected to a nozzle (140, not shown)). Thus (and after the ejection of discrete portions of the pressurized medical fluid (F), the high-pressure medical pumping device is ready for the next pumping cycle.

[0205] List of reference numerals 1. Shell 2. Fluid storage tank, storage container 3 Pumping Chamber 4 Inlet Valves 5 risers 5A internal end 5B External End 6 nozzles 7. Devices for storing potential energy 8 outlet valves 9 Hollow cylinders, tubes 10 retainers 11 (Riser) Fluid passage 12 containers 101 High-Pressure Medical Pumping Device 102 fluid inlet 103 Fluid Outlet 104 Check Valve 110 pumping unit 111 Pump Cylinder 112 Pump Room Fluid opening in pump chamber 113 120 piston The first end of the 121 piston The second end of the 122 piston Fluid passage for pistons 123 130 storage 140 nozzles 150 drive units 160 housing 170 retains structure 100 portable inhalation devices F Liquids, Fluids

Claims

1. A handheld inhalation device for delivering a nebulized medical active fluid (F) for inhalation therapy, comprising: (a) A housing (1) having a side facing the user; (b) A nozzle (6) for generating an atomized aerosol by the collision of at least two liquid jets, the nozzle (6) being securely attached to the user-facing side of the housing (1) so as to be fixed relative to the housing (1); (c) A fluid reservoir (2) disposed within the housing (1) for containing the medically active fluid; as well as (d) A pumping unit, arranged within the housing (1), the pumping unit having: -The upstream end, which is fluidly connected to the fluid reservoir (2); and -The downstream end is fluidly connected to the nozzle (6). The pumping unit is adapted to pump the medical active fluid (F) from the fluid reservoir (2) to the nozzle (6). The pumping unit further includes: (i) A riser (5) having an upstream end and a downstream end, wherein the riser (5) is adapted to serve as a piston in the pumping unit; (ii) A retainer (10) located downstream of the riser, securely attached to the user-facing side of the housing (1) to be fixed relative to the housing (1) for retaining the riser; (iii) A hollow cylinder (9) located upstream of the riser (5), wherein the upstream end of the riser (5) is inserted into the cylinder (9) such that the cylinder (9) is capable of longitudinal movement on the riser (5); and (iv) A lockable device (7) for storing potential energy when locked and for releasing the stored energy when unlocked, the device (7) being disposed outside the cylinder (9) and mechanically coupled to the cylinder (9) such that unlocking the device (7) causes the cylinder (9) to move longitudinally toward the downstream end of the pumping unit. The retainer (10) and the riser (5) are one-piece units.

2. The inhalation device according to claim 1, wherein, The retainer (10) and the riser (5) comprise an injection-moldable polymer material, optionally at least one thermoplastic injection-moldable polymer material.

3. The inhalation device according to any one of the preceding claims, wherein, The retainer (10) and the riser (5) are made of the same injection-moldable polymer material.

4. The high-pressure medical pumping device according to claim 2 or 3, wherein, The injection-moldable polymer material is selected from the group consisting of polyoxymethylene (POM), polyetheretherketone (PEEK), and polyphenylene oxide (PPO / PPE), preferably PEEK.

5. The high-pressure medical pumping device according to any one of claims 2 to 4, wherein, The injection-moldable polymer material is a mixture or blend comprising at least one injection-moldable material and at least one other injection-moldable polymer material, wherein the at least one injection-moldable material is selected from the group consisting of PEEK, PPO / PPE, and POM, and the at least one other injection-moldable polymer material is selected from the group consisting of: acrylonitrile butadiene styrene copolymer (ABS), acrylonitrile styrene acrylate (ASA), styrene acrylonitrile copolymer (SAN), polyacrylic acid (such as polymethyl methacrylate (PMMA)), and acrylonitrile butadiene styrene copolymer (ABS). Polyamide, polylactic acid (polylactide, PLA), polybenzimidazole (PBI), polycarbonate (PC), polyethersulfone (PES), polyoxymethylene (POM), polyetheretherketone (PEEK), polyetherimide (PEI), polyethylene (PE) (such as ultra-high molecular weight polyethylene (UHMWPE), high-density polyethylene (HDPE), medium-density polyethylene (MDPE), low-density polyethylene (LDPE)), polyphenylene ether (PPO), polyphenylene sulfide (PPS), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), polyvinylidene fluoride (PVDF), and polytetrafluoroethylene (PTFE).

6. The high-pressure medical pumping device according to any one of claims 2 to 5, wherein, The at least one injection-molded material is polyetheretherketone (PEEK).

7. The high-pressure medical pumping device according to any one of the preceding claims, wherein, The one-piece unit, including the riser (5) and the retainer (10), comprises a composite material, which includes an injection-moldable material.

8. The high-pressure medical pumping device according to any one of the preceding claims, wherein, The riser is essentially composed of the injection-molded material.

9. The inhalation device according to any one of the preceding claims, wherein, The riser includes a fluid channel fluidly connecting the upstream end of the riser to the downstream end of the riser for delivering the medically active fluid. Optionally, the diameter of the fluid channel is selected in the range of about 0.1 mm to about 1 mm.

10. The inhalation device according to any one of the preceding claims, wherein, The diameter of the riser is selected in the range of approximately 1 mm to approximately 3 mm.

11. The inhalation device according to any one of the preceding claims, wherein, The length of the riser is selected in the range of approximately 10 mm to approximately 30 mm.

12. The inhalation device according to any one of the preceding claims, wherein, The nozzle includes an impact nozzle.

13. The inhalation device according to any one of the preceding claims, wherein, The pumping unit is a high-pressure pumping unit, which is adapted to discharge fluid (F) at a pressure of at least 50 bar.

14. The inhalation device according to any one of the preceding claims, wherein, The device (7) for storing potential energy is a spring that has a load of at least 40 N in the deflected state.

15. The inhalation device according to any one of the preceding claims, adapted to deliver the atomized medical active aerosol in discrete units, wherein, Each pumping cycle delivers one unit, optionally wherein the unit of the aerosol contains 2 µL to 150 µL of liquid phase.

16. A handheld inhalation device for delivering a nebulized medical active fluid (F) for inhalation therapy, comprising: (a) A housing (1) having a user-facing side, the housing further comprising a container configured for attaching a riser (5); (b) A nozzle (6) for generating an atomized aerosol by the collision of at least two liquid jets, the nozzle (6) being securely attached to the user-facing side of the housing (1) so as to be fixed relative to the housing (1); (c) A fluid reservoir (2) disposed within the housing (1) for containing the medically active fluid; as well as (d) A pumping unit, arranged within the housing (1), the pumping unit having: -The upstream end, which is fluidly connected to the fluid reservoir (2); and -The downstream end is fluidly connected to the nozzle (6). The pumping unit is adapted to pump the medical active fluid (F) from the fluid reservoir (2) to the nozzle (6). The pumping unit further includes: (i) Riser (5), which as a whole includes: The riser section has an upstream end and a downstream end; A retainer section (10) located at the downstream end of the riser section is attached to the container of the housing and securely attaches the riser (5) to the user-facing side of the housing (1) so as to be fixed relative to the housing (1). (ii) a hollow cylinder (9) located upstream of the riser (5), wherein the upstream end of the riser (5) is inserted into the cylinder (9) such that the cylinder (9) is capable of longitudinal movement along the riser section; and (iii) A lockable device (7) for storing potential energy when locked and for releasing the stored energy when unlocked, the device (7) being arranged outside the cylinder (9) and mechanically coupled to the cylinder (9) such that unlocking the device (7) causes the cylinder (9) to move longitudinally toward the downstream end of the pumping unit.

Images