WO2025224091A1

WO2025224091A1 - Pumping device comprising multiple valves

Info

Publication number: WO2025224091A1
Application number: PCT/EP2025/060903
Authority: WO
Inventors: Gord DAENEN; Steven Dudley; Jürgen Rawert
Original assignee: Invox Belgium NV
Current assignee: Invox Belgium NV
Priority date: 2024-04-23
Filing date: 2025-04-22
Publication date: 2025-10-30
Anticipated expiration: 2026-10-23

Abstract

The disclosure provides a high-pressure medical pumping device (1) for providing discrete portions of a medical fluid (F) in pressurized form, wherein the pumping device (1) comprises an outlet check valve (5) comprising a self-closing mechanism and an inlet check valve (4) configured to be closed by medical fluid (F) flowing back in the upstream direction.

Description

TITLE: PUMPING DEVICE COMPRISING MULTIPLE VALVES

Description

FIELD OF THE INVENTION

The invention relates to the field of pumping devices for inhalation devices for delivering a medically active fluid in aerosolized form for inhalation therapy. In particular, the invention relates to high-pressure medical pumping device comprising an inlet valve and an outlet valve, wherein the outlet valve comprises a self-closing mechanism.

BACKGROUND OF THE INVENTION

Nebulizers or other aerosol generators for liquids are known from the art since a long time ago. Amongst others, such devices are used in medical science and therapy. There, they serve as inhalation devices for the application of active ingredients in the form of aerosols, i.e. small liquid droplets embedded in a gas. Such an inhalation device is known e.g. from document EP 0 627 230 Bl. Components of this inhalation device include a reservoir in which the liquid that is to be aerosolized is contained; a pumping device for generation of a pressure being sufficiently high for nebulizing; as well as an atomizing device in the form of a nozzle. By means of the pumping device, the liquid is drawn in a discrete amount, i.e. not continuously, from the reservoir, and fed to the nozzle. The pumping device works without propellant and generates pressure mechanically.

A known embodiment of such an inhalation device is presented in document WO 91/14468 Al. In such a device, the pressure in the pumping chamber which is connected to the housing is generated by movement of a moveable hollow piston. The piston is moveably arranged inside the immobile cylinder or pumping chamber. The (upstream arranged) inlet of the hollow piston is fluidically connected to the interior of the reservoir (reservoir pipe section). Its (downstream arranged) tip leads into the pumping chamber. Furthermore, a check valve that inhibits a back flow of liquid into the reservoir is arranged inside the tip of the piston. For filling the piston, the same is directly connected with its upstream end to the reservoir. By pulling out the piston of the pumping chamber provided inside a hollow cylinder, its interior volume is enlarged, such that an increasing under pressure is built up inside the pumping chamber. This pressure propagates through the hollow piston into the reservoir, such that liquid is sucked from the same into the piston. At the same time, said valve opens at its tip, since the pressure inside the reservoir is higher than inside the (yet empty) pumping chamber. The pumping chamber is being filled. At the same time, a spring is loaded, and locked at the motion’s end when the moveable piston has reached its lower dead centre (in the case of a vertically arranged device) and the pumping chamber is filled.

The spring can be manually unlocked. The stored energy is then abruptly released. The piston is again pushed in direction of the pumping chamber and into the same, thus decreasing its interior volume. The check valve is now closed, such that a growing pressure builds up inside the pumping chamber, since the liquid is inhibited from flowing back into the reservoir. Eventually, this pressure results in ejection of the liquid from the nozzle which is arranged at the downstream end of the pumping chamber.

In order to face the risk of a reverse flow of already ejected liquid or even outside air, a further check valve, subsequently being called outlet valve, can be arranged at the downstream end of the pumping chamber just before the nozzle, allowing emitted liquid to pass, but blocking incoming gas or liquid.

The piston is arranged inside the pressure spring, which is designed as helical spring, thus limiting its outside diameter. Also because of the typically small volume (e.g. 15 pl), the piston is designed with a thin interior (and often also exterior) diameter.

An improved inhalation device utilising a non-moveable piston is disclosed in WO 2018/197730 Al. The device overcomes some of the drawbacks of the prior art.

SUMMARY OF THE INVENTION

In a first aspect, the disclosure relates to a high-pressure medical pumping device (1) for providing discrete portions of a medical fluid (F) in pressurized form, wherein the pumping device (1) comprises a fluid inlet (2); a fluid outlet (3); and a pumping unit (10) fluidically connecting the fluid inlet (2) with the fluid outlet (3) and being adapted to generate the discrete portions of the medical fluid (F) in pressurized form and to convey the discrete portions of the medical fluid (F) in a downstream direction from the fluid inlet (2) to the fluid outlet (3); wherein the pumping unit (10) comprises a pump cylinder (11) comprising a pump chamber (12) located within the pump cylinder (11), the pump chamber (12) comprising a fluid opening (13) and a piston opening (14); a piston (20) comprising a first end (21) and a second end (22) located opposite of the first end, wherein the piston (20) is at least partly located within the pump chamber (12) of the pump cylinder (11) such that at least the first end (21) of the piston is located within the pump chamber (12), and wherein the piston (20) and the pump cylinder (11) are arranged for back and forth stroke movement of at least one of the piston (20) and the pump cylinder (1) relative to each other, wherein the piston (20) comprises a fluid channel (23) fluidically connecting the first end (21) of the piston with the second end (22) of the piston and being adapted to convey the medical fluid (F) from the first (21) or second end (22) of the piston to the corresponding opposite end of the piston; an inlet check valve (4) fluidically connecting the fluid inlet (2) with the pumping unit (10) and being permeable in the downstream direction; and an outlet check valve (5) fluidically connecting the fluid outlet (3) with the pumping unit (10) and being permeable in the downstream direction, wherein the outlet check valve (5) comprises a self-closing mechanism; and wherein the inlet check valve (4) is adapted (arranged) to be closed by medical fluid (F) flowing back in the upstream direction.

In a further aspect, the present disclosure provides for an inhalation device (100) for the administration of a medical fluid (F) in aerosolized form comprising a high-pressure medical pumping device according to the disclosure.

In yet a further aspect, the disclosure provides for the use of an inhalation device comprising a high-pressure pumping device according to the disclosure for the generation of an inhalable aerosol.

DESCRIPTION OF THE DRAWINGS

Figure 1A depicts an inhalation device.

Figure IB Depicts a zoomed in version of the outlet side of the high pressure medical pumping unit.

Figure 2A depicts a part of an inhalation device comprising a high-pressure medical pumping device, comprising a duckbill valve as an outlet check valve with a self-closing mechanism. Figure 2B depicts a part of an inhalation device comprising a high-pressure medical pumping device, comprising an umbrella valve as an outlet check valve with a self-closing mechanism.

Figure 2C depicts a part of an inhalation device comprising a high-pressure medical pumping device, comprising a ball valve with a biasing element in the form of a spring as outlet check valve with self-closing mechanism.

DETAILED DESCRIPTION OF THE INVENTION

The following terms or expressions as used herein should normally be interpreted as outlined in this section, unless defined otherwise by the description or unless the specific context indicates or requires otherwise:

The terms ‘a’, ‘an’ or ‘the’ do not exclude a plurality; i.e. the singular forms ‘a’, ‘an’ and ‘the’ should be understood as to include plural referents unless the context clearly indicates or requires otherwise. In other words, all references to singular characteristics or limitations of the present disclosure shall include the corresponding plural characteristic or limitation, and vice versa, unless explicitly specified otherwise or clearly implied to the contrary by the context in which the reference is made. The terms ‘a’, ‘an’ and ‘the’ hence have the same meaning as ‘at least one’ or as ‘one or more’ unless defined otherwise.

The expressions, ‘one embodiment’, ‘an embodiment’, ‘a specific embodiment’ and the like mean that a particular feature, property or characteristic, or a particular group or combination of features, properties or characteristics, as referred to in combination with the respective expression, is present in at least one of the embodiments of the disclosure. The occurrence of these expressions in various places throughout this description do not necessarily refer to the same embodiment Moreover, the particular features, properties or characteristics may be combined in any suitable manner in one or more embodiments.

The terms ‘essentially’, ‘about’, ‘approximately’, ‘substantially” and the like in connection with an attribute or value include the exact attribute or the precise value, as well as any attribute or value typically considered to fall within a normal range or variability accepted in the technical field concerned. For example, the term ‘about’ in connection with a value or range of values as used herein shall mean that such value or range of values includes typical deviations from such values of up to +/- 5% (abs.J, or up to about +/-4%, or up to +/- 3% up to +/- 2%, up to +/- 1%, up to +/- 0.5%. In a first aspect, the disclosure relates to a high-pressure medical pumping device (1) for providing discrete portions of a medical fluid (F) in pressurized form. The high-pressure medical pumping device is in particular suitable to be used in an inhalation device, preferably a hand-held inhalation device. Said inhalation device allows for the aerosolization of a medical fluid for inhalation therapy.

The term "medical fluid” or "medically active fluid” as used herein is to be interpreted broadly and encompasses a fluid or preferably a liquid that may be applied or administered to a subject, for example by inhalation, and that preferably is physiologically and/or pharmaceutically acceptable. In some embodiments, the medically active fluid may be waterbased 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 ingredients liquid such as a solution or dispersion. In some embodiments, the medically active fluid may be a liquid composition comprising an aqueous or alcoholic liquid solvent or, in other words, vehicle and optionally at least one medically active ingredient and optionally at least one pharmaceutically acceptable excipient wherein the term "excipient” as used herein means a compound which may be comprised by the medically active fluid including, but are not limited to, one or more buffering agents to regulate or control pH of the solution such as hydrochloric acid, chelating agents such as EDTA, salts such as sodium chloride, taste-masking agents, surfactants, lipids, antioxidants, co-solvents, and combinations thereof, which may be used to enhance or improve solubility as well as preservatives such as benzalkonium chloride.

Suitable excipients are known to the skilled person and are described, e.g. in standard pharmacopoeias such as U.S.P. or Ph. Eur., or in the Handbook of Pharmaceutical Excipients, 6th ed. Rowe et al, Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009.

In some embodiments, the medically active fluid may simply be water or an aqueous solution of sodium chloride. In further embodiments, the medically active fluid may comprise at least one active pharmaceutical ingredient, for example selected from the groups of long acting muscarinic antagonists (LAMAs), for example tiotropium, aclidinium, umeclidinium and glycopyrrolium, or long acting beta antagonists (LABAs) for example olodaterol, vilanterol, or inhalable glucocorticoids (ICSs) such as predinisolone, ciclesonide, beclomethasone and others. The medically active fluid as described above may be provided in discrete portions in pressurized form by the high-pressure medical pumping unit of the present disclosure. The terms "discrete portion” or "portion” or "unit dose” are used herein synonymously and refer to a predetermined amount in which the medical fluid is provided by the present medical pumping device or, more specifically, the corresponding pumping unit at a single time or, in other words, upon a single actuation of the pumping device.

In some embodiments, the medically active fluid to be compressed and conveyed by the present pumping device may be free from any propellant such as a gaseous propellant and in some embodiments is not provided or stored in a reservoir in the form of a mixture comprising such a propellant

In some embodiments, one discrete portion of the medical fluid has a volume selected in the range of from about 1 pl to about 1000 pL or even above or from about 1 pL to about 750 pL or to about 500 pL or from about 1.5 pL to about 500 pL or to about 400 pL or from about 2 pL to about 300 pL or to about 200 pL or from about 2 pL to about 150 pL or from about 5 pL to about 100 pL or from about 10 pL to about 75 pL or from about 15 pL to about 50 pL or from about 20 pL to about 40 pL or to about 30 pL.

The high pressure medical pumping device (1) according to the disclosure comprises a fluid inlet (2), a fluid outlet (3) and a pumping unit (10) fluidically connecting the fluid inlet (2) with the fluid outlet (3) and being adapted to generate the discrete portions of the medical fluid (F) in pressurized form and to convey the discrete portions of the medical fluid (F) in a downstream direction from the fluid inlet (2) to the fluid outlet (3).

The term "fluid inlet” as used herein is also to be interpreted broadly and generally refers to an opening or inlet through which the medical fluid to be pressurized and conveyed can enter the pumping device, for example in the form of tubing or other fluidic connection. In some embodiments, the medical fluid may enter the present pumping device via the fluid inlet in non-pressurized form or in a form in which the fluidic pressure of the medical fluid is lower than the fluidic pressure of the medical fluid leaving the pumping device via the fluid outlet as described below after being pressurized. Accordingly, the fluid inlet of the pumping device is also sometimes referred to as a "low pressure end” of the pumping unit from which the medical fluid is conveyed in a downstream direction towards the fluid outlet by the pumping unit as described below. Correspondingly, the term "fluid outlet” as used herein generally refers to an opening or outlet to which the medical fluid in pressurized form is conveyed to and through which can exit the pumping device, for example in the form of tubing or other fluidic connection. In some embodiments, the medical fluid may exit the present pumping device via the fluid outlet in pressurized form or in a form in which the fluidic pressure of the medical fluid is higher than the pressure of the medical fluid entering the pumping device via the fluid inlet as described above before being pressurized. Accordingly, the fluid outlet of the pumping device is also sometimes referred to as a "high pressure end” of the pumping unit to which the medical fluid is conveyed in a downstream direction from the fluid inlet by the pumping unit as described below.

In some embodiments of the presenthigh-pressure medical pumping device, the liquid inlet is fluidically connected or connectable to a reservoir for holding the medical fluid. The term "reservoir” as used herein may be interpreted broadly as relating to a container which is suitable for holding or storing the medical fluid that is to be pressurized and dispensed. In some embodiments, the reservoir may be in the form of a dimensionally stable or flexible container, for example a dimensionally stable or flexible bottle with an outlet opening which may be fluidically connected to the fluid inlet of the pumping device. In some embodiments, the reservoir may hold the medical fluid in non-pressurized form or, in other words, at atmospheric pressure. In further embodiments, the reservoir may be firmly attached to or connected with the fluid inlet of the pumping device. In alternative embodiments, however, the reservoir may be designed to be removably attached to the fluid inlet of the present inhalation device.

The pumping unit of the high-pressure medical pumping device (1) comprises: a pump cylinder (11) comprising a pump chamber (12) located within the pump cylinder (11), the pump chamber (12) comprising a fluid opening (13) and a piston opening (14); and a piston (20) comprising a first end (21) and a second end (22) located opposite of the first end, wherein the piston (20) is at least partly located within the pump chamber (12) of the pump cylinder (11) such that at least the first end (21) of the piston is located within the pump chamber (12), and wherein the piston (20) and the pump cylinder (11) are arranged for back and forth stroke movement of at least one of the piston (20) and the pump cylinder (12) relative to each other, an inlet check valve (4) fluidically connecting the fluid inlet (2) with the pumping unit (10) and being permeable in the downstream direction; and an outlet check valve (5) fluidically connecting the fluid outlet (3) with the pumping unit (10) and being permeable in the downstream direction

The piston (20) used in the pump chamber of the high pressure medical pumping device (1) of the disclosure additionally comprises a fluid channel (23) which is fluidically connecting the first end (21) of the piston with the second end (22) of the piston and which conveys the medical fluid (F) from the first (21) or second end (22) of the piston to the corresponding opposite end of the piston.

The inlet check valve (4) of the pumping unit (10) of the high pressure medical pumping device (1) is configured or adapted or arranged to be closed by medical fluid (F) flowing back in the upstream direction.

The outlet check valve (5) of the pumping unit (10) of the high pressure medical pumping device (1) according to the disclosure comprises a self-closing mechanism.

The outlet check valve (5) may be any suitable valve that comprises a self-closing mechanism.

In the context of the present disclosure a check valve with self-closing mechanism refers to a check valve that closes and seals immediately after the pressure opening the valve is gone, preferably due to a force effective on said valve or a part of the valve. This selfclosing mechanism may be realized due to material properties, i.e. an elastic, pre-shaped material which immediately returns to the original position or by using a biasing means to exert a force to close the valve. In some embodiments, the self-closing valve is resilient in that due to a closing force, it reverts to the original position or shape. In some embodiments, the outlet check valve (5) is resiliently biased in a closed position.

A check valve comprising a self-closing mechanism preferably operates in any orientation of the valve or device. Preferably, the opening of the valve is only dependent on the pressure difference between the upstream and downstream side of the valve.

Examples of self-closing valves based on material properties include for example duckbill valves and umbrella valves. An alternative example for a check valve with a self-closing mechanism is a ball valve with a biasing element for exerting a biasing force on the ball of the ball check valve. Other valves utilizing biasing elements as a self-closing mechanism may be used as well. Said biasing element may be any kind of biasing element. An example of a biasing element is a spring. In contrast to a ball valve with a biasing element, a regular ball valve without a biasing element is not a check valve with a self-closing mechanism in the sense of the present disclosure.

Accordingly, in one embodiment the disclosure relates to a high-pressure medical pumping device (1) as defined above, wherein the outlet check valve (5) comprises a ball checkvalve, a duckbill valve or an umbrella valve. In a particular embodiment, the outlet check valve (5) comprises a ball check valve comprising a ball and a biasing element (6) for exerting a biasing force on the ball of the ball check valve. In a preferred embodiment, the biasing element is a spring.

In some embodiments, the outlet check valve comprises a ball check valve, wherein the ball check valve comprises a ball and a biasing element in the form of a spring. The ball may be of any suitable material, in particular an elastic deformable material, preferably polymeric materials.

Preferably, the ball of the outlet check valve (5) is a plastic or rubber ball. In the case of a rubber ball, the ball may be made of natural or synthetic rubber. In some embodiments the ball of the outlet check valve (5) as defined above is made from synthetic rubber. In particular embodiments the ball is made of EPDM rubber. In case of plastic, suitable materials include, but are not limited to, polypropylene (PP), polyethylene (PE), or polyoxymethylene (POM).

The spring may be made from any suitable material. Preferably, the spring is a metallic spring. In some embodiments the spring is a steel spring in particular a stainless steel spring. Preferably, the spring exerts a force between about 0.05 N up to 1 N on the ball valve. In particular embodiments, the spring exerts a force between 0.08 and 0.125 N. In an alternative embodiment, the spring exerts a force between 0.08 and 0.125 N. In a further embodiment, the spring exerts a force between 0.32 to 0.59 N on the ball of the outlet check valve (5).

In preferred embodiments, the inlet check valve (4) does not comprise a self-closing mechanism as defined above. As noted above, the inlet check valve is adapted or arranged to be closed by medical fluid (F) flowing back in the upstream direction. As such, the medical fluid flowing back is exerting a force to close the valve.

The inlet check valve (4) may be a ball valve and said ball valve is closed by medical fluid (F) flowing back in the upstream direction in addition to gravitational forces. Accordingly, in one embodiment of the disclosure, the high-pressure medical pumping device (1) is as defined above, wherein the inlet check valve (4) does not comprise a self-closing mechanism as defined above. In a particular embodiment, the inlet check valve (4) comprises a ball check valve. In a preferred particular embodiment, the inlet check valve (4) comprises a ball check valve, wherein the ball check valve does not comprise a biasing element for exerting a biasing force on the ball of the ball check valve. In particular embodiments, the inlet check valve (4) does not comprise a spring.

In a particular embodiment, the disclosure relates to a high-pressure medical pumping device

(I) for providing discrete portions of a medical fluid (F) in pressurized form, wherein the pumping device (1) comprises:

- a fluid inlet (2);

- a fluid outlet (3); and

- a pumping unit (10) fluidically connecting the fluid inlet (2) with the fluid outlet (3) and being adapted to generate the discrete portions of the medical fluid (F) in pressurized form and to convey the discrete portions of the medical fluid (F) in a downstream direction from the fluid inlet (2) to the fluid outlet (3); wherein the pumping unit (10) comprises:

- a pump cylinder (11) comprising a pump chamber (12) located within the pump cylinder

(II), the pump chamber (12) comprising a fluid opening (13) and a piston opening (14); and

- a piston (20) comprising a first end (21) and a second end (22) located opposite of the first end, wherein the piston (20) is at least partly located within the pump chamber (12) of the pump cylinder (11) such that at least the first end (21) of the piston is located within the pump chamber (12), and wherein the piston (20) and the pump cylinder (11) are arranged for back and forth stroke movement of at least one of the piston (20) and the pump cylinder (11) relative to each other, wherein the piston (20) comprises a fluid channel (23) fluidically connecting the first end (21) of the piston with the second end (22) of the piston and being adapted to convey the medical fluid (F) from the first (21) or second end (22) of the piston to the corresponding opposite end of the piston; and - an inlet check valve (4) fluidically connecting the fluid inlet (2) with the pumping unit (10) and being permeable in the downstream direction, wherein the inlet check valve (4) comprises a ball check valve and preferably does not comprise a biasing element (6) for exerting a biasing force on the ball of the ball check valve; and

- an outlet check valve (5) fluidically connecting the fluid outlet (3) with the pumping unit (10) and being permeable in the downstream direction, wherein the outlet check valve (5) comprises a ball check valve comprising a ball and a biasing element (6) for exerting a biasing force on the ball of the ball check valve, specifically a spring.

The inventors found that a pumping device comprising an outlet check valve with a selfclosing mechanism improves the device. The use of an outlet check valve with a self-closing mechanism improves the aerosol and increases safety of the device. An outlet valve with selfclosing mechanism further improves protection from contamination of the device, in particular microbial contamination.

The presenthigh-pressure medical pumping device further comprises a pumping unit fluidically connecting the fluid inlet with the fluid outlet and to generate the discrete portions of the medical fluid in pressurized form and to convey the discrete portions of the medically active fluid (in a downstream direction) from the fluid inlet to the fluid outlet.

The term "fluidically connecting” as used herein is to be interpreted broadly and refers to all structures through which a fluid or liquid, specifically the medical fluid, may be transported from one part of the device to another part of the device, preferably without significant loss of the liquid to be transported. Such a fluidic connection may be implemented, for example, by a non-permeable encased structure such as tubing through which the fluid may be transported or conveyed or by another fluidic structure that allows for the lossless transport of such fluid as, for example by the pumping unit of the presenthigh-pressure pumping device.

In some embodiments, the pumping unit functions as a piston pump, also referred to as plunger pump comprising a piston or plunger, which is axially displaceable within a hollow cylinder. The inner segment of the hollow cylinder, in which at least a segment of the piston moves, forms a pumping chamber which has a variable volume, depending on the position of the piston relative to the cylinder. Accordingly, the pumping unit of the present high-pressure pumping device comprises a pump cylinder comprising a pump chamber located within the pump cylinder, the pump chamber comprising a fluid opening. As described above, the pump cylinder may also be referred to as a "hollow cylinder” corresponding to a part or member which is hollow in the sense that it comprises an internal void which has a cylindrical shape, or which has a segment having a cylindrical space. In other words, and as is applicable to other types of piston pumps, it is not required that the external shape of the respective part or member is cylindrical. Moreover, the expression "hollow cylinder” does not exclude an operational state of the respective part or member in which the "hollow” space may be filled with material, e.g. with a medical fluid, such as a liquid to be nebulised.

The pump cylinder or, more specifically, the pump chamber, further comprises a fluid opening (in addition to the opening of the pump cylinder into which the piston is introduced (in the operational state). The fluid opening may be, depending on the design of the pumping unit as described further below, fluidically connected or connectable with either the fluid inlet or the fluid outlet of the pumping device and, accordingly, may either be located at the low-pressure side of the pumping unit to allow the medical fluid to be conveyed and pressurized to enter the pump chamber, or may be located at the high-pressure side of the pumping unit to allow the pressurized discrete portions of medical fluid to exit the pump chamber.

The presenthigh-pressure medical pumping device further comprises a piston, specifically a longitudinal piston, comprising a first end and a second end located opposite of the first end, wherein the piston is at least partly located within the pump chamber of the pump cylinder such that at least the first end of the piston is located within the pump chamber. The piston, in some embodiments, is a longitudinal cylinder with preferably a circular cross-sectional area with a first end to be introduced into the internal void of the pump cylinder. In some embodiments, the first and the second end of the piston may be located within the pump chamber (in the operational state of the pumping unit) which means that the entire piston is located within the cylindrical internal void (pump chamber) of the piston. In alternative embodiments, the piston may be located within the pump chamber (in the operational state) such that only the first end is located within the pump chamber and, accordingly, the second end is located outside of the pump chamber (in the operational state).

The piston and the pump cylinder of the pumping unit are arranged for back-and-forth stroke movement of at least one of the piston and the pump chamber relative to each other. During such back-and-forth stroke movement of either the piston relative to the pump chamber or of the pump chamber relative to the piston or of both, with movement of the piston and the pump chamber relative to one another, the volume of the pump chamber as defined by the corresponding (internal surface) of the pump chamber and (the outer surface of) the first end of the piston varies according to the corresponding position of the piston within the pump chamber during the longitudinal back-and-forth stroke movement This allows for the compression and conveyance of the medical fluid when introduced into the pump chamber during a stroke-like movement of either the piston or the pump cylinder or of both relative to each other, in which the volume of the pump chamber is reduced.

In some embodiments, one pumping cycle of the pumping unit comprised by the present high-pressure medical pumping device starts with a situation in which the piston is positioned maximally within (i.e., in the innermost position of) the pump cylinder (resulting in a minimal volume of the pump chamber) and comprises a relative movement of the piston to a position in which it is maximally extracted from the pump cylinder (repulsive movement; resulting in a maximum volume of the pump chamber) followed by a relative back movement of the piston to its initial position (propulsive movement). In some embodiments, one discrete portion of the medical fluid in pressurized form to be delivered by the present high- pressure medical pumping device is delivered per pumping cycle. In some embodiments, the medical fluid is sucked into the pump chamber during the repulsive movement of the piston relative to the pump cylinder and is pressurized and expelled from the pump chamber during the propulsive movement of the pumping cycle.

As described above, the volume of the pump chamber may vary in the course of the strokelike movement of either one of the piston or the pump cylinder. In some embodiments, the pump chamber (as defined by the inner walls of the pump cylinder and the first end of the piston) of the presenthigh-pressure medical pumping device may have a (maximal) volume selected within the range of from about 1 pL to about 100 pL, preferably of from about 5 pL to about 50 pL, or from about 15 pL to about 30 pL. For the avoidance of doubt, this volume refers to the maximum volume of the pump chamber in an operational state of the pumping unit in which the piston is in its outermost position relative to the pump cylinder.

In some embodiments, the diameter of the piston (as measured perpendicular to the main axis of the piston) is essentially constant over and preferably corresponds or essentially corresponds the inner diameter of the pump chamber over the entire segment of the piston introduced into the pump chamber. The piston of the pumping unit comprises a fluid channel fluidically connecting the first end of the piston with the second end of the piston and being adapted to convey the medical fluid from the first or second end of the piston to the corresponding opposite end of the piston. This fluid channel or, more specifically, the second end of this fluid channel, may be, depending on the design of the pumping unit as described further below, fluidically connected or connectable with either the fluid inlet or the fluid outlet of the pumping device and, accordingly, may either be located at the low-pressure side of the pumping unit to allow the medical fluid to be conveyed and pressurized to enter the pump chamber, or may be located at the high-pressure side of the pumping unit to allow the pressurized discrete portions of medical fluid to exit the pump chamber. In the first case the (second end of) the fluid channel may be in fluidic connection with the fluid inlet of the pumping device and in the second case the (second end of) the fluid channel may be in fluidic connection with the fluid outlet of the pumping device, in both cases optionally via a check valve as described above in connection with fluid opening of the pump cylinder.

In some embodiments, the fluid channel may extend along the entire length of the piston from the first end of the piston to the opposite second end the piston. In further embodiments, the fluid channel may have a circular or non-circular cross-sectional shape, preferably, a circular cross-sectional shape. In yet further embodiments, the fluid channel may have a main axis extending from the first end of the piston to the second end of the piston, which, in some embodiments, corresponds to the main axis of the piston.

In some embodiments of the presenthigh-pressure medical pumping device, the fluid opening of the pump cylinder may be fluidically connected or connectable to the fluid inlet of the pumping device (and optionally to the reservoir) and located downstream of the fluid inlet of the pumping device and the second end of the piston may be fluidically connected or connectable to the fluid outlet of the pumping device. In further embodiments, the pumping unit may comprise a check valve and the check valve may be located within the pump cylinder and/or may be positioned adjacent to the fluid inlet of the pump cylinder. In these embodiments, the piston may be arranged in a fixed position within the pumping unit such that the piston is immobile during back-and-forth stroke movement of the pump chamber. For example, the piston may be attached to the housing of either the pumping device, or, in some embodiments, of the inhalation device comprising such pumping device. In some embodiments, the piston may be attached to or fixed by a corresponding holding structure. In alternative embodiments of the presenthigh-pressure medical pumping device, the fluid opening of the pump cylinder may be fluidically connected or connectable to the fluid outlet of the pumping device and located upstream of the fluid outlet of the pumping device and the second end of the piston may be connected or connectable to the fluid inlet of the pumping device. In further embodiments, the pumping unit may have a check valve located within the piston, and optionally positioned at the first end of the piston. In these embodiments, the pump cylinder may be arranged in a fixed position within the pumping unit such that the pump cylinder is immobile during back-and-forth stroke movement of the piston. For example, the pump cylinder may be attached to the housing of either the pumping device, or, in some embodiments, of the inhalation device comprising such pumping device. In some embodiments, the pump cylinder may be attached to or fixed by a corresponding holding structure.

In some embodiments of the presenthigh-pressure medical pumping device, one discrete portion of the medical fluid in pressurized form is generated by one stroke movement of at least one of the piston and the pump cylinder.

The high-pressure medical pumping device (1) according to the disclosure is suitable to provide discrete portions of medical fluid (F) in pressurized form of at least about 100 bar or higher. In particular, the pumping unit is adapted to provide the discrete portions of the medical fluid (F) in pressurized form at a pressure of at least about 100 bar.

Adaptation of the pumping unit to provide discrete portions of the medical fluid (F) in pressurized form at a pressure of at least about 100 bar involves use of particular materials, geometry and sizes of the components.

In some embodiments the piston comprises or is made from an injection-mouldable material, preferably a polymeric injection-mouldable material. Any injection mouldable material may be used, however, polymeric materials, in particular thermoplastic polymeric materials are preferred. The material may also be a mix of materials instead of a single material.

In some embodiments of the disclosure, the piston consists of said injection-mouldable material.

Suitable injection mouldable materials include, but are not limited to, polyoxymethylene (POM), polyether ether ketone (PEEK), and polyphenylene oxide (PPO/PPE), particularly polyether ether ketone (PEEK). In case of mixtures, the suitable materials include, but are not limited to, PEEK, PPO/PPE or POM and at least one further injection-mouldable polymeric material selected from the group consisting of polyacrylic acids, (such as polyfmethyl methacrylate (PMMA)), acrylonitrile butadiene styrene (ABS), polyamides, polylactic acid (polylactide, PLA), polybenzimidazole PBI), polyether sulfone (PES), polyoxymethylene (POM), polyether ether ketone (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 oxide (PPO), polyphenylene sulphide (PPS), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), polyvinylidene fluoride PVDF) and polytetrafluorethylene (PTFE).

In some embodiments, the piston is made of a composite material comprising an injection mouldable material. In such embodiments, the injection-mouldable material may be an injection-mouldable material as defined above. In preferred embodiments, the composite material is an injection-mouldable material as defined above comprising a non-injection- mouldable material.

Suitable non-injection mouldable materials are known to the skilled person and include, but are not limited to, glass, metals, ceramics, 2 DPA-1 (for example in the form of fibres, beads, granules or other suitable structures) or other solid materials, for example carbon fibre.

The pump cylinder is preferably made of a non-compressible or non-deformable material. The pump cylinder may comprise or essentially consist of a metal or a polymeric material selected from the group consisting of acrylonitrile butadiene styrene (ABS), acrylonitrile styrene acrylate (ASA), styrene acrylonitrile copolymer (SAN), acrylonitrile butadiene styrene (ABS), polyamides, polylactic acids (polylactide, PLA), polybenzimidazoles (PBI), polycarbonates (PC), polyether sulfone (PES), polyoxymethylene (POM), polyether ether ketone (PEEK) and polyphenylene oxide (PPO).

In particular embodiments, the pump cylinder comprises or essentially consists of a thermoplastic polymeric material selected from polyoxymethylene (POM; CAS Registry number 9002-81-7), polyether ether ketone (PEEK; CAS Registry number 29658-26-2), and poly(p-phenylene oxide (PPO) (also known as poly-p-phenylene ether (PPE); CAS Registry number 25134-01-4). In yet further embodiments, the pump cylinder comprises or essentially consists of PEEK, either in the form of a composite material or in the form of a non-composite material, i.e. without comprising any non-inj ection-mouldable materials. In further embodiments, the pump cylinder may comprise the thermoplastic polymeric material in the form of a composite material as described in detail above.

In one of the preferred embodiments, the pumping unit is a high-pressure pumping unit and configured to operate, or to expel 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 from about 2 bar to about 1000 bar, or from about 50 bar to about 250 bar, respectively. In some embodiments, the operating pressure may be in the range of at least about 150 bar or at least about 175 or at least about 200 bar, for example from about 100 bar to about 1000 bar or even 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, the operating pressure is the pressure at which the pumping unit expels fluid, in particular a medically active fluid or liquid, such as an inhalable aqueous liquid formulation of a pharmacologically active ingredient, from its pumping chamber, in a downstream direction, i.e., towards a nozzle. In this context, the expression "adapted to operate" means that the components of the pumping unit are selected with respect to the materials, the dimensions, the quality of the surfaces and the finish are selected such as to enable operation at the specified pressure.

In particular embodiments, the pumping unit (10) of the high-pressure medical pumping device (1) is adapted to provide the discrete portions of the medical fluid (F) in pressurized form ata pressure of at least about 100 bar, or of at least about 150 bar, or of at least about 175 bar or of at least about 200 bar.

In some embodiments, the pumping unit (10) of the high-pressure medical pumping device (1) is adapted to provide the discrete portions of the medical fluid (F) in pressurized form at a pressure of between about 75 bar and about 250 bar, or of between about 100 bar and 200 bar, or of between about 125 bar and 175 bar.

In some embodiments, the pumping unit (10) of the high-pressure medical pumping device (1) is adapted to provide the discrete portions of the medical fluid (F) in pressurized form at a pressure of about 100 bar, or of about 150 bar, or of about 175 bar or of about 200 bar. Preferably, the high-pressure medical pumping device (1) according to the disclosure is configured to be comprised by an inhalation device (100) for the administration of the medical fluid (F) in aerosolized form for inhalation. In some embodiments, the high-pressure medical pumping device (1) as defined above is comprised by an inhalation device (100). Said inhalation device is preferably a handheld inhalation device.

In order for the high-pressure medical pumping device (1) according to the disclosure to be adapted to be comprised in an inhalation device, the device is preferably connectable to other parts of the inhalation device. In particular, the high-pressure medical pumping device (1) is preferably fluidically connectable to a reservoir and a nozzle. The high-pressure medical pumping device is preferably also integratable with the priming and/or release mechanism of an inhalation device.

Accordingly, in some embodiments, the disclosure relates to a high-pressure medical pumping device (1) as defined above, wherein the fluid outlet (3) is fluidically connectable or fluidically connected to a nozzle (40) for discharging and optionally aerosolizing the conveyed medical fluid (F) in pressurized form. Said nozzle may be any suitable kind of nozzle. In some embodiments said nozzle is an impingement-type nozzle.

In embodiments in which the presenthigh-pressure medical pumping device is comprised by an inhalation device, such a nozzle may be adapted to aerosolize or, in other words, to nebulize the pressurized discrete portions of medical fluid. Suitable nozzles in this regard comprise but are not limited to, for example, swirl nozzles, impingement-type nozzles, nozzle plates (Raleigh principle), flat fan nozzles, hollow cone nozzles, full cone nozzles, solid stream nozzles and others.

The pumping unit of the high-pressure medical pumping device may be setup in any suitable way. In one embodiment of the disclosure the fluid opening (13) of the pump cylinder (12) is fluidically connected to the fluid inlet (2) of the pumping device (1) via the inlet check valve (4) and located downstream of the fluid inlet (2) of the pumping device (1) and wherein the second end (22) of the piston (20) is fluidically connected to the fluid outlet (3) of the pumping device via the outlet check valve (5).

In this embodiment of the disclosure, the inlet check valve (4) may be comprised by the pump cylinder (11) and/or is positioned adjacent to the fluid opening (13) of the pump chamber. In this case, adjacent to the fluid opening refers to adjacent in an upstream or downstream direction. The inlet check valve (4) controls flow between the pump chamber and a reservoir of medical fluid (F).

In some embodiments of the disclosure as defined above, the piston (20) is arranged in a fixed position within the pumping unit (1) such that the piston (20) is immobile during back- and-forth stroke movement of the pump chamber (12).

In an alternative embodiment of the disclosure, the fluid opening (13) of the pump cylinder (11) is fluidically connected to the fluid outlet (3) of the pumping device (1) via the outlet check valve (5) and located upstream of the fluid outlet (3) of the pumping device (1) and wherein the second end (22) of the piston (20) is fluidically connected to the fluid inlet (2) of the pumping device (1) via the inlet check valve (4).

In some embodiments, the inlet check valve may be comprised by the piston. The inlet check valve may be comprised anywhere in the piston, preferably, the inlet check valve (4) is positioned at the first end or second end of the piston.

In some embodiments of the disclosure, the inlet check valve (4) is comprised by the piston (20), and optionally positioned at the first end (21) or the second end (22) of the piston (20).

In some embodiments of the disclosure as defined above, the piston is immobile. In a different embodiment of the disclosure, the piston is moveable and the pump cylinder is immobile during a pump cycle.

In some embodiments, the presenthigh-pressure medical pumping device or, more specifically, the pumping unit comprises a drive unit adapted for driving the stroke movement of at least one of the piston and the pump cylinder. The drive unit allows for the propulsion or retraction of at least one of the piston and the pump cylinder relative to each other, especially during the part of the pumping cycle in which the volume of the pump chamber is reduced and, accordingly, the discrete portion of the medical fluid is to compressed. The drive unit may be in any suitable form that allows for the generation of a stroke-like back-and-forth movement of the piston relative to the pump cylinder. In some embodiments, it may comprise a motor, such as an electrical motor or a means for the storage and release of potential energy to be transformed into kinetic energy of the piston and/or the cylinder, for example a spring, a compressed gas or a compressed elastomeric material.

In particular embodiments, the drive unit may be adapted to exert a driving force on at least one of the piston and pump cylinder of at least about 30 N or at least about 35 N or at least about 40 N or selected within the range of from about 50 N to about 200 N or to about 150 N or to about 100 N. In further particular embodiments, the drive unit may be adapted to exert a driving force on at least one of the piston and pump cylinder in the range of from about 30 N to about 150 N or to about 100 N, or selected within the range of from about 35 N to about 80 N.

In further embodiments, the pumping unit of the presenthigh-pressure medical pumping device may comprise a lockable means for storing potential energy when locked and for releasing the stored energy when unlocked, the means being arranged outside of and being mechanically coupled to at least one of the pump cylinder and the piston such that unlocking the means results in a propulsive longitudinal movement of at least one of the pump cylinder and the piston towards the corresponding other one of the pump cylinder and the piston. In some embodiments, the means for storing potential energy as referred to above may comprise a spring, such as a spring made of steel or another elastic metal or material. In particular embodiments, such as a spring may have a load within the ranges described above in connection with driving force of the drive unit of at least about 30 N or at least about 35 N or at least about 40 N or selected within a range of from about 50 N to about 200 N or to about 150 N or to about 100N in a deflected state or selected in the range of from about 30 N to about 150 N or to about 100 N, or selected within the range of from about 35 N to about 80 N in a deflected state. In further embodiments, the pumping unit may further comprise a lock for locking the lockable means. This may allow the driving means to be tensioned or loaded and, in a separate step, to be triggered by unlocking the lockable means for storing potential energy to drive the pumping unit

In a further aspect, the present disclosure provides for an inhalation device for the administration of a medical fluid in aerosolized form comprising a high-pressure medical pumping device as described in detail above. As already mentioned, in some embodiments, the inhalation device according to this aspect of the disclosure may be a mobile inhalation device, more particularly a hand-held inhalation device that may be carried and used by a user holding and operating it with one or both hands of such user. Such inhalation devices are, for example, disclosed in documents WO 91/14468 Al or WO 2018/197730 Al as already referred to above.

For the avoidance of doubt, it should be noted that all embodiments, features, definitions, explanations and combinations thereof as disclosed in connection with the pumping device of the first aspect of the disclosure also apply to this second aspect of the disclosure as well as all further aspects of the disclosure although not being repeated in connection with the present and all further aspects of the disclosure.

The disclosure relates in addition to the following numbered items:

1. A high-pressure medical pumping device (1) configured to provide discrete portions of a medical fluid (F) in pressurized form, wherein the medical pumping device (1) comprises:

- a fluid inlet (2);

- a fluid outlet (3); and

- a pumping unit (10) fluidically connecting the fluid inlet (2) with the fluid outlet (3) and configured to generate the discrete portions of the medical fluid (F) in pressurized form and to convey the discrete portions of the medical fluid (F) in a downstream direction from the fluid inlet (2) to the fluid outlet (3); wherein the pumping unit (10) comprises:

- a pump cylinder (11) comprising a pump chamber (12) located within the pump cylinder (11), the pump chamber (12) comprising a fluid opening (13) and a piston opening (14);

- a piston (20) comprising a first end (21) and a second end (22) located opposite to the first end, wherein the piston (20) is at least partly located within the pump chamber (12) ofthe pump cylinder (11) such that at least the firstend (21) ofthe piston is located within the pump chamber (12), and wherein the piston (20) and the pump cylinder (11) are arranged for back and forth stroke movement of at least one of the piston (20) and the pump cylinder (1) relative to each other, wherein the piston (20) comprises a fluid channel (23) fluidically connecting the first end (21) of the piston with the second end (22) of the piston and configured to convey the medical fluid (F) from the first (21) or second end (22) of the piston to the corresponding opposite end of the piston;

- an inlet check valve (4) fluidically connecting the fluid inlet (2) with the pumping unit (10), the inlet check valve allowing unidirectional flow in the downstream direction; and - an outlet check valve (5) fluidically connecting the fluid outlet (3) with the pumping unit (10), the outlet check valve allowing unidirectional flow in the downstream direction, wherein the outlet check valve (5) comprises a self-closing mechanism; and wherein the inlet check valve (4) is configured to be closed by medical fluid (F) flowing back in the upstream direction. The high-pressure medical pumping device (1) according to item 1, wherein the outlet check valve (5) comprises a ball check valve, a duckbill valve or an umbrella valve. The high-pressure medical pumping device (1) according to item 2, wherein the outlet check valve (5) comprises a ball check valve comprising a ball and a biasing element (6) for exerting a biasing force on the ball of the ball check valve, specifically a spring. The high-pressure medical pumping device (1) according to any one of the preceding items, wherein the inlet check valve (4) comprises a ball check valve. The high-pressure medical pumping device (1) according to item 4, wherein the inlet check valve (4) does not comprise a biasing element for exerting a biasing force on the ball of the ball check valve, specifically a spring. The high-pressure medical pumping device (1) according to any one of the preceding items, wherein the pumping unit (10) is configured to provide the discrete portion of the medical fluid (F) in pressurized form at a pressure of at least about 100 bar, or of at least about 150 bar, or of at least about 175 bar or of at least about 200 bar. The high-pressure medical pumping device (1) according to any one of the preceding items wherein the pumping device (10) is configured to be comprised by an inhalation device (100) for the administration of the medical fluid (F) in aerosolized form for inhalation. The high-pressure medical pumping device (1) according to any one of the preceding items, wherein the fluid outlet (3) is fluidically connected to a nozzle (7) configured to discharge the discrete portion of the medical fluid (F) and optionally aerosolizing the discrete portion of the medical fluid (F) in pressurized form. The high-pressure medical pumping device (1) according to any one of the preceding items, wherein the fluid opening (13) of the pump cylinder (11) is fluidically connected to the fluid inlet (2) of the pumping device (1) via the inlet check valve (4) and the fluid opening (13) is located downstream of the fluid inlet (2) of the pumping device (1) and wherein the second end (22) of the piston (20) is fluidically connected to the fluid outlet (3) of the pumping device via the outlet check valve (5).

10. The high-pressure medical pumping device (1) according to any one of the preceding items, wherein the inlet check valve (4) is located within the pump cylinder (11) and/or is positioned adjacent to the fluid opening (13) of the pump chamber.

11. The high-pressure medical pumping device (1) according to any one of the preceding items, wherein the piston (20) is fixed within the pumping unit (1) such that the piston (20) is immobile during back-and-forth stroke movement of the pump chamber (12).

12. The high-pressure medical pumping device (1) according to any one of items 1 to 8, wherein the fluid opening (13) of the pump cylinder (11) is fluidically connected to the fluid outlet (3) of the pumping device (1) via the outlet check valve (5) and the fluid opening (13) is located upstream of the fluid outlet (3) of the pumping device (1) and wherein the second end (22) of the piston (20) is also fluidically connected to the fluid inlet (2) of the pumping device (1) via the inlet check valve (4).

13. The high-pressure medical pumping device (1) according to any one of the preceding items, wherein the inlet check valve (4) is located within the piston (20), and optionally positioned at the first end (21) or the second end (22) of the piston (20).

14. The high-pressure medical pumping device (1) according to any one of the preceding items, wherein the pump cylinder (11) is fixed within the pumping unit (10) such that the pump cylinder (11) is immobile during back-and-forth stroke movement of the piston (20).

15. The high-pressure medical pumping device (1) according to any one of items 3 to 14, wherein the biasing element of the ball check valve exerts a biasing force on the ball within a range of about 0.05 N up to 1 N.

16. The high-pressure medical pumping device (1) according to item 15, wherein the biasing element of the ball check valve exerts a biasing force on the ball within a range of about 0.08 and 0.125 N, optionally between about 0.32 to 0.59 N. 17. The high-pressure medical pumping device (1) according to any one of the preceding items, wherein the piston (20) comprises an injection-mouldable polymeric material, specifically wherein the injection-mouldable material is a thermoplastic polymeric material.

18. The high-pressure medical pumping device (1) according to item 17, wherein the injection-mouldable polymeric material is selected from the group consisting of polyoxymethylene (POM), polyether ether ketone (PEEK), polyphenylene oxide (PPO/PPE), and combinations thereof, particularly polyether ether ketone (PEEK).

19. The high-pressure medical pumping device (1) according to items 17 or 18, wherein the injection-mouldable polymeric material is a mixture or blend comprising at least one injection-mouldable material selected from the group consisting of PEEK, PPO/PPE and POM and at least one further injection-mouldable polymeric material selected from the group consisting of polyacrylic acids, (such as poly(methyl methacrylate (PMMA)), acrylonitrile butadiene styrene (ABS), polyamides, polylactic acid (polylactide, PLA), polybenzimidazole PBI), polyether sulfone (PES), polyoxymethylene (POM), polyether ether ketone (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 oxide (PPO), polyphenylene sulphide (PPS), polypropylene (PP), polystyrene (PS), polyvinyl chloride (PVC), polyvinylidene fluoride PVDF) polytetrafluorethylene (PTFE), and combinations thereof.

20. The high-pressure medical pumping device (1) according to any one of items 17 to 19, wherein the piston comprises a composite material comprising an injection-mouldable material.

21. The high-pressure medical pumping device according to item 20, wherein the composite material further comprises a non-injection-mouldable material.

22. The high-pressure medical pumping device (1) according to item 20 or 21, wherein the composite material comprises at least one non-injection-mouldable material selected from the group consisting of glass, metals, ceramics, 2 DPA-1 (for example in the form of fibres, beads, granules or other suitable structures) or other solid materials, for example carbon fibre, and combinations thereof. 23. The high-pressure medical pumping device according to any one of the items 17 to 22, wherein the piston essentially consists of the injection-mouldable material.

24. The high-pressure medical pumping device (1) according to any one of the preceding items, wherein the pump cylinder (11) comprises or essentially consists of a non- compressible and/or non-deformable material, for example stainless steel, PEEK, ..., preferable PEEK.

25. The high-pressure medical pumping device (1) according to any one of items 3 to 23, wherein the ball of the outlet check valve (5) comprises or essentially consists of an elastically deformable material.

25. An inhalation device (100) for the administration of a medical fluid (F) in aerosolized form comprising a high-pressure medical pumping device according to any one of items 1 to 24.

The high-pressure medical pumping device is further described with reference to the figures.

Figure 1A depicts a high-pressure medical pumping device (1) in an inhalation device (lOO)withouta self-closing outlet valve. The device comprises a reservoir (30) for a medical fluid) which is fluidically connected to the high-pressure medical pumping device (1). Said high pressure medical pumping device comprises a fluid inlet (2), fluidically connected to the reservoir (30), and a fluid outlet, fluidically connected to a nozzle (7). Said nozzle is preferably an impingement type nozzle, however, the nozzle may be any suitable nozzle.

The high-pressure medical pumping device further comprises an inlet valve, in figure 1 depicted in the form of a ball valve. The ball valve provides access for the fluid to the pump chamber (12). In this embodimentthe fluid opening (13) is connected with the fluid inlet (2) of the device. The alternative embodiment, wherein the fluid opening (13) of the pumping unit (10) is connected to the fluid outlet (13) is not depicted.

The pump chamber is formed by the pump cylinder (11) and the piston (20). The pump chamber (12) itself is of variable size. Depending on the embodiment of the inhalation device, either the piston (20) or the pump cylinder (11) is moveable. In the depicted embodiment, the pump cylinder (11) is moveable. The piston (20) is fluidically connected to the pump chamber (12) via the first end (21) and connected to the pump cylinder (11) by the piston opening (14) of the pump cylinder (11). The second end (22) of the piston connects to the outlet valve (5). In order to generate the fluidic connection between outlet valve (5) and pump chamber (12) the piston (20) includes a fluid channel (23).

Figure IB shows a detailed view of the outlet section of the high-pressure medical pumping device. The section shows the outlet valve (5) in form of a ball valve, which allows the medical fluid (F) to pass to the nozzle (7) and the fluid outlet

Figures 2A, 2B and 2C show different versions of the outlet area of the high-pressure medical according to the present disclosure.

In Figure 2 A the outlet valve (5) is a duckbill valve as self-closing valve. The duckbill check valve opens upon release of the fluid (F) and allows the fluid to pass towards the nozzle (7) and fluid outlet.

Figure 2B shows an umbrella valve as self-closing valve instead of a duckbill valve as an outlet valve (5).

The embodiment depicted in Figure 2C shows a ball valve with a biasing element (6) in the form of a spring as the outlet valve (5). The force of the fluid (F) opens the outlet valve (5) and the force of the biasing element (6) enables the self-closing mechanism after release of the fluid. By adapting the force of the spring the release of the fluid can be better controlled and improved.

Figure Legend

F fluid

1 high pressure medical pumping device

2 fluid inlet

3 fluid outlet

4 inlet check valve

5 outlet check valve

6 biasing element 7 nozzle

10 pumping unit

11 pump cylinder

12 pump chamber 13 fluid opening

14 piston opening

20 piston

21 first end

22 second end

23 fluid channel

30 fluid reservoir

100 inhalation device

Claims

Dr i z.'rrurrcr Claims

- a fluid inlet (2);

- a fluid outlet (3); and

(11), the pump chamber (12) comprising a fluid opening (13) and a piston opening (14);

- a piston (20) comprising a first end (21) and a second end (22) located opposite to the first end, wherein the piston (20) is at least partly located within the pump chamber (12) of the pump cylinder (11) such that at least the first end (21) of the piston is located within the pump chamber (12), and wherein the piston (20) and the pump cylinder (11) are arranged for back and forth stroke movement of at least one of the piston (20) and the pump cylinder (1) relative to each other, wherein the piston (20) comprises a fluid channel (23) fluidically connecting the first end (21) of the piston with the second end (22) of the piston and configured to convey the medical fluid (F) from the first (21) or second end (22) of the piston to the corresponding opposite end of the piston;

- an inlet check valve (4) fluidically connecting the fluid inlet (2) with the pumping unit (10), the inlet check valve allowing unidirectional flow in the downstream direction; and

- an outlet check valve (5) fluidically connecting the fluid outlet (3) with the pumping unit (10), the outlet check valve allowing unidirectional flow in the downstream direction, wherein the outlet check valve (5) comprises a self-closing mechanism; and wherein the inlet check valve (4) is configured to be closed by medical fluid (F) flowing back in the upstream direction.

2. The high-pressure medical pumping device (1) according to claim 1, wherein the outlet check valve (5) comprises a ball check valve, a duckbill valve or an umbrella valve.

3. The high-pressure medical pumping device (1) according to claim 2, wherein the outlet check valve (5) comprises a ball check valve comprising a ball and a biasing element (6) for exerting a biasing force on the ball of the ball check valve, specifically a spring.

4. The high-pressure medical pumping device (1) according to any one of the preceding claims, wherein the inlet check valve (4) comprises a ball check valve.

5. The high-pressure medical pumping device (1) according to claim 4, wherein the inlet check valve (4) does not comprise a biasing element for exerting a biasing force on the ball of the ball check valve, specifically a spring.

6. The high-pressure medical pumping device (1) according to any one of the preceding claims, wherein the pumping unit (10) is configured to provide the discrete portion of the medical fluid (F) in pressurized form at a pressure of at least about 100 bar, or of at least about 150 bar, or of at least about 175 bar or of at least about 200 bar.

7. The high-pressure medical pumping device (1) according to any one of the preceding claims, wherein the pumping device (10) is configured to be comprised by an inhalation device (100) for the administration of the medical fluid (F) in aerosolized form for inhalation.

8. The high-pressure medical pumping device (1) according to any one of the preceding claims, wherein the fluid outlet (3) is fluidically connected to a nozzle (7) configured to discharge the discrete portion of the medical fluid (F) and optionally aerosolizing the discrete portion of the medical fluid (F) in pressurized form.

9. The high-pressure medical pumping device (1) according to any one of the preceding claims, wherein the fluid opening (13) of the pump cylinder (11) is fluidically connected to the fluid inlet (2) of the pumping device (1) via the inlet check valve (4) and the fluid opening (13) is located downstream of the fluid inlet (2) of the pumping device (1) and wherein the second end (22) of the piston (20) is fluidically connected to the fluid outlet (3) of the pumping device via the outlet check valve (5).

10. The high-pressure medical pumping device (1) according to any one of the preceding claims, wherein the inlet check valve (4) is located within the pump cylinder (11) and/or is positioned adjacent to the fluid opening (13) of the pump chamber.

11. The high-pressure medical pumping device (1) according to any one of the preceding claims, wherein the piston (20) is fixed within the pumping unit (1) such that the piston (20) is immobile during back-and-forth stroke movement of the pump chamber (12).

12. The high-pressure medical pumping device (1) according to any one of claims 3 to 11, wherein the biasing element of the ball check valve exerts a biasing force on the ball within a range of about 0.05 N up to 1 N.

13. The high-pressure medical pumping device (1) according to claim 12, wherein the biasing element of the ball check valve exerts a biasing force on the ball within a range of about 0.08 and 0.125 N, optionally between about 0.32 to 0.59 N.

14. The high-pressure medical pumping device (1) according to any one of claims 3 to 13, wherein the ball of the outlet check valve (5) comprises or essentially consists of an elastically deformable material.

15. An inhalation device (100) for the administration of a medical fluid (F) in aerosolized form comprising a high-pressure medical pumping device according to any one of claims 1 to 14.