Field of disclosure

The present invention lies in the field of dosing units for an ambulatory infusion system. The invention lies further in the field of ambulatory infusion systems that include a dosing unit. Furthermore, the invention lies in the field of methods initializing a dosing unit.

Background, prior art

Ambulatory infusion devices are well known in the art for example in the therapy of Diabetes Mellitus by Continuous Subcutaneous Insulin Infusion ( CSI I ) as well as in pain therapy or cancer therapy and are available from a number of supplies, such as Roche Diagnostics GmbH , Germany, or Medtronic M ini Med Inc. , CA, USA.

The EP 1 970677A1 discloses a system with a miniaturized metering piston pump with a dosing cylinder that is repeatedly coupled to and filled from a larger reservoir, followed by coupling the dosing cylinder to an infusion site and infusing the liquid drug out of the dosing cylinder in incremental steps and over an extended time period via displacing a piston. For alternatively coupling the dosing cylinder to the reservoir and the infusion site, a valve system is proposed. Reference is made to the EP 1 970677A1 for the basic operational principle and design of a dosing unit in accordance with the present document.

Summary of disclosure

To ensure safe operation, the piston must be in sliding and sealing engagement with the inner wa ll of a metering cavity ( bore) of the dosing cylinder. In order to achieve a sealing engagement and accordingly liquid tightness, a sealing member of the piston needs to be biased against the inner wa ll of the metering cavity. At least the sealing member of the piston is made from a comparably soft materia l, such as an elastomers or thermoplastic elastomers.

While the dosing unit is typically designed as disposable and its actual application time ( i. e. the time in which it is used for drug infusion ) lies in a typical range of some days, the dosing unit may be stored for a time period of up to one year or even more prior to being actually used. (Thermoplastic) elastomers, however, are known to significantly creep if tensioned or biased over an extended time period. Creep of the piston in the sealing member results in a reduced fluidic tightness or even com plete loss of fluidic tightness. Maintaining fluidic tightness over the storing time and application time is accordingly a crucial and critical issue.

It is an overall object of the present invention to improve the situation regarding fluidic tightness of a dosing unit. This overall object is ach ieved by the subject of the independent claims. Particularly favourable em bodiments are defined by the dependent claims and further exemplary embodiments as described in this document. The invention is based on the insight that fluidic tightness, while being essential during application of the dosing unit for drug infusion, is not required for the preceding storing period. For the storing period, the dosing unit may accordingly be in a configuration where is relieved, i.e. unbiased or biased only to an extent where creep may be ignored. I n this configuration, however, the engagement between piston and dosing cylinder may not be tight.

According to an aspect, the overall object is achieved by providing a dosing unit for use in an ambulatory infusion system. A dosing unit in accordance with the present disclosure includes a dosing cylinder and a piston. The piston is arranged inside the dosing cylinder. The piston is arranged in a sliding displaceable manner along a displacement axis. The inner volume of the dosing cylinder in wh ich the piston is arranged is also referred to as "metering cavity". The metering cavity typically has a cylindrical or section-wise cylindrical shape and extends along the displacement axis.

The piston is convertible from a storing configuration into an operational configuration. A circumferential sealing member of the piston is mechanically relieved in the storing configuration and is in sealing and sliding engagement with a circumferential inner surface of the dosing cylinder in the operational configuration.

The dosing unit further includes a config uration switch member. The configuration switch member is typically in operative mechanical coupling with the piston. The configuration switch member is movable relative to the piston from a storing position into an operational position, thereby switching the piston configuration from the storing configuration to the operational configuration.

A force may be exerted onto the circumferential sealing member by the configuration switch member directly or via the piston as intermediate component. For this purpose, the piston may be radially elastic.

Storing the piston and in particular its circumferential sealing member in the relieved storing configuration has the before-discussed advantage that the circumferential sealing member does not creep over time. Accordingly, the time period for which the dosing unit may be stored prior to its use without adversely affecting its characteristics and specifications is increased.

Favourably, the switching from the storing configuration to the operational configuration is irreversible. In this way, it is ensured that the operational configuration is maintained over the application time of the dosing unit. In some em bodiments, the dosing unit includes a valve unit, the valve unit being reversibly switchable between a filling configuration and a draining configuration, wherein the valve unit fluidic couples the dosing cylinder with a filling port in the filling configuration and with a draining port in the draining configuration. In such em bodiments that include a valve unit, the dosing unit may especially be desig ned in accordance with the disclosure of the EP 1 970677A1 as discussed before.

The present invention, however, may equally be applied to dosing units and am bulatory infusion systems of different general designs. The dosing cylinder may especially realized or include a typically cylindrical drug cartridge, such as an insulin cartridge, that comprises a liquid volume in a range of, e.g. 1 ml to 4 ml, sufficient for uninterrupted infusion therapy for a num ber of days or even a week or more. Like for the cylinder of a dosing unit in accordance with the EP 1 970677A1 , the liquid is administered from the cartridge substantially continuously and in incremental steps. Such cartridge, however, is not refilled from a larger reservoir but discarded after emptying. In such embodiments, a valve unit is not required. Corresponding infusion pum ps are also referred to as syringe-driver pumps.

In this document, the following terminology is used: The terms "proximal" and "distal" indicate directions along the displacement axis. A piston movement into the proximal direction decreases the liquid volume (also referred to as "active volume") within the metering cavity, while a piston movement in the distal direction increases the active volume. In operation, liquid is according ly drawn into the metering cavity by a piston movement in the distal direction and expelled out of the metering cavity by a piston movement into the proximal direction. The terms "inwards" and "outwards" refer to radial directions perpendicular to the displacement axis. The inwards direction points from the periphery of the dosing cylinder towards the displacement axis. The outwards direction points from the displacement axis towards the periphery.

In some embodiments, the piston is a two-element piston with a hard piston element and a soft piston element. In such embodiments, the soft piston element acts as sealing member, with a circumferential surface of the soft piston member contacting the inner circumferential surface of the metering cavity, thus establishing a sealing and sliding engagement in the operational configuration.

In some embodiments with a two-element piston, the piston is injection-moulded and the soft piston element is made from thermoplastic elastomers. This type of embodiment where the piston is made by two-com ponent injection moulding is particularly favourably regarding large scale manufacturing costs. For thermoplastic elastomers, however, creeping is particularly critical. Therefore, the present invention is particularly favourable in this context. Alternatively, however, the piston may be generally made from a hard materia l, e.g . hard plastics, and a soft piston element is provided as dedicated separate component, e.g. as miniaturized elastomeric O-ring seal and mounted to the hard piston element only during assembly.

In some embodiments, the configuration switch member is mova ble from the storing position into the operational position by displacing the configuration switch member relative to the piston along the displacement axis. Via this relative displacement, the piston is radially extended, thus biasing the circumferential sealing member against the circumferential inner surface of the metering cavity and establishing the sealing.

Alternatively or additionally, the configuration switch member may, fully or in part, be radially movable with respect to the displacement axis for switching from the storing configuration to the operational configuration. In some embodiments, the configuration switch member is arranged, at least partly, within a bore or recess of the piston. For such embodiments, movement of the configuration switch member from the storing position to the operational position is associated with a displacement of the configuration switch member within the bore or recess. Favourably, the configuration switch member is arranged in a bore or recess in a proximal section of the piston. The arrangement of the configuration switch member in a bore or recess of the piston allows a particular compact design of the dosing unit.

In some embodiments, the configuration switch member overlaps, in axial direction, with the circumferential sealing member. It is generally favourable to axially align the force that is exerted by the configuration switch member onto the circumferential sealing member in the operational configuration with the circumferential sealing member.

I n some embodiments, the configuration switch member includes a spring member, the spring member being biased in the storing position and being fully or partly relieved upon movement from its storing position into its operational position For such embodiments, the movement of the spring member from its initial biased ( i.e. deflected ) configuration towards its released ( i. e. non -deflected ) configuration results in the circumferential sealing member being biased against the circumferential inner wall of the dosing cylinder. The corresponding biasing force is accordingly a spring force. As will be discussed in more detail below in the context of exemplary embodiments, the spring member may especially be realised by spring-loaded arms that extend parallel to the displacement axis.

In some embodiments, the piston and the configuration switch member are designed to force-lock and /or positively lock the configuration switch member relative to the piston in the operational position. Force locking may especially be realized via a radial force acting between the circumferential inner surface of the metering cavity, the piston, the piston. and the configuration switch member. Here, the soft piston element serves as resilient biasing member and is arranged between the metering cavity wall and the configuration switch member. The configuration switch member is favourably made from a hard material, such as hard plastics. For positive locking of the configuration switch member relative to the piston, interacting hooks, catches, protrusion, recesses and the like may be provided .

In some embodiments, the configuration switch member includes a stop member, the stop member being axially spaced apart from the piston in the storing position. Movement of the configuration switch member from the storing position into the operational position is associated with a movement of the stop member towards the piston. The stop member may especially be an e.g. disk-shaped radial protrusion that is arranged proximal of the piston front surface in the storing position. The stop member hitting the piston surfaces stops the movement of the config uration switch member in the operational position.

In some em bodiments with a stop member, the configuration switch member is arranged to be displaced from the storing position into the operationa l position via the stop member interacting with a blocking surface of the dosing cylinder.

In some em bodiments, the piston includes or is operatively mechanically coupled to a threaded piston member, the threaded piston member being arranged to engage a threaded counter-member for displacing the piston. The threaded piston member may, e.g. include an outer thread that engages a threaded counter-member in form of an inner thread of a rotational drive sleeve. The drive sleeve may be part of the dosing unit or of a separate drive un it. Alternatively, an inner thread as threaded counter member may be provided as part of the dosing cylinder.

According to a further aspect, the overall object is achieved by providing an ambulatory infusion system. Typically, such am bulatory infusion system is designed to be continuously carried by a user over an extended time period and concealed from view. The am bulatory infusion system includes a dosing unit as described before as well as further below in the context of exemplary embodiments. The ambulatory infusion system further includes an electric drive unit, the drive unit operatively mechanically coupling to the piston for displacing the piston inside the metering cavity. I n embodiments where the dosing unit includes a valve unit as discussed before, the drive unit may further couple to the valve unit for switching the valve unit between the filling configuration and the draining configuration.

According to a still further object, the overall object is ach ieved by providing a method for initializing a dosing unit of an am bulatory infusion system. The dosing un it of such ambulatory infusion system includes a dosing cylinder and a piston. The piston is arranged sliding displaceable along a displacement axis inside the dosing cylinder.

The method includes the steps of: a ) providing the dosing unit with a piston of the dosing unit being in a storing configuration, wherein a circumferential sealing member of the piston is mechanically relieved in the storing configuration; b) moving a configuration switch member relative to the piston from a storing position into an operationa l position.

By moving the configuration switch member, the piston is switched from the storing configuration into an operational configuration. A sealing engagement of the circumferential sealing member and a circumferential inner surface of the metering cavity is thereby established.

In some embodiments, the step of moving the configuration switch member relative to the piston from the storing position into the operational position includes moving the piston in a proximal direction with a movement of the configuration switch member in the proximal direction being blocked by an interaction of the configuration switch member and the dosing cylinder.

Exemplary embodiments

In the following, exemplary embodiments are discussed in more detail with additional reference to the figures.

Fig. 1 shows an exemplary dosing unit in accordance with the present disclosure with the piston being in the storing configuration.

Fig. 2 shows the dosing unit of Fig. 1 with the piston being in the operational configuration. Fig. 3 shows a further exem plary dosing unit in accordance with the present disclosure with the piston being in the storing configuration.

Fig. 4 shows the dosing unit of Fig. 3 with the piston being in the operational configuration.

In the figures, the proximal direction is indicated by "p" wh ile the distal direction is indicated by "d". Identical or substantially identical elements in various figures are generally referenced only once.

In the following, reference is first made to Fig. 1 . Fig. 1 shows an exemplary embodiment of a dosing unit 1 in accordance with the present disclosure together with a drive sleeve 2 of an electric drive unit. The dosing unit 1 includes a stationary part 1 0, a dosing cylinder 1 1 , and a piston 1 2. Additionally, the dosing unit 1 includes a configuration switch member 3.

The dosing cylinder 1 1 is rotatable and sealingly supported in a recess or dosing cylinder bore ( not referenced ) of the stationary part 1 0. The dosing cylinder 1 1 has a longitudinal symmetry axis which defines the displacement axis A.

The piston 1 2 has a body 1 20 that generally extends along the displacement axis A. Like the stationary part 1 0 and the dosing cylinder 1 1 , the piston body 1 20 is made of hard plastics. In a proximal section of the piston 1 2, a circumferential sealing member 1 21 is arranged . The circumferential sealing member 1 21 is made from a comparatively soft materia l, in particular a thermoplastic elastomer (TPE), and is formed with the piston body 1 20 in an integral way by two-component injection moulding. In com bination, the body 1 20 and the sealing member 1 21 have a plane proximal front surface.

The dosing cylinder 1 1 is generally hollow and of tubular shape with an open distal and a closed proximal front surface. The inner volume of the dosing cylinder 1 1 forms a metering cavity of circular cross section. The metering cavity accordingly forms an elongated bore or recess of the dosing cylinder 1 0. The metering cavity has a metering cavity main section 1 1 0 and a proximal metering cavity recess 1 1 1 . As compared to the metering cavity ma in section 1 1 0, the proximal metering cavity recess 1 1 1 is substantially shorter and has a substantially smaller inner diameter. The metering cavity main section 1 1 0 and the proximal metering cavity recess 1 1 1 are concentric with and extend along the displacement axis A. In operation, a variable volume V of the metering cavity 1 1 0, 1 1 1 , proximal of the piston 1 2 and the configuration switch member 3 , is filled with liquid (also referred to as "active volume"). Alternatively, the metering cavity may not be two-parted but have a cylindrical shape of a single dia meter. Distal from the piston body 1 20, the piston 1 2 has a threaded piston member 1 23 that is realized as inner-threaded tubular recess. The inner thread ( not shown ) of the threaded piston member 1 23 is, in an operational state, in engagement with a threaded counter- member 20 that is realized as outer-threaded pin of the drive sleeve 2 (outer thread not shown ). The piston 1 2 and the cylinder dosing cylinder 1 1 are further in engagement via an anti-rotation member as known in the art ( not shown ). By rotating the drive sleeve 2, the piston 1 2 is accordingly linearly displaceable along the axis A within the dosing cylinder 1 1 , in proximal or distal direction, respectively, thereby decreasing or increasing respectively the active volume V.

By a coupling mechanism ( not shown ), the dosing cylinder 1 1 is further selectively operatively and mechanically coupleable with the drive sleeve 2. When rotating the drive sleeve 2 in the coupled or engaged state, both the dosing cylinder 1 1 and the piston 1 2 are accordingly rotated in combination relative to the stationary part 1 0, substantially or fully without relative movement between the dosing cylinder 1 0 and the piston 1 1 . When rotating the drive sleeve 2 in the uncoupled or disengaged state, only the piston 1 2 is axially displaced as explained before, while the dosing cylinder 1 1 does not move.

In a circumferential wall (side wall ) at the proximal end of the proximal metering cavity recess 1 1 1 , a dosing cylinder aperture ( not visible) is arranged . An inlet aperture and an outlet aperture ( both not visible) are further arranged in the stationary part 1 0. In dependence of the rotational position of the cylinder relative to the stationary part 1 0, the dosing cylinder aperture may fluidic couple the active volume V with the inlet aperture, or, alternatively, with the outlet aperture. Favourably, stops, blocks or the like are present that limit the movement of the dosing cylinder 1 1 relative to the stationary part 1 0. In the following, operation of the configuration switch member 3 and associated features is explained in more detail. A distal section ( not separately referenced ) of the configuration switch member 3 is received in a config uration switch member recess 1 22 in a proximal area of the piston 1 2. The configuration switch member 3 has a cylindrical or pin -shaped configuration switch member body 30 and a disk-shaped stop member 32, with the disk diameter corresponding to and being favourably slightly smaller than the outer diameter of the piston 1 2 and the inner diameter of the distal metering cavity 1 1 0, respectively. The configuration switch member 3 is typically made from hard plastics.

The dia meters of the configuration switch member recess 1 22 and the configuration switch member body 30 are favourably adjusted such that the configuration switch member 3 is displaceable with respect to the piston 1 2 along the displacement axis A under substantial friction between the configuration switch member recess 1 22 and the configuration switch member body 30. Adjacent to and distal from the stop member 32, the config uration switch member 3 has a bracing member 3 1 that is exemplarily realized as ring -shaped protrusion ( i.e. section of larger diameter) . A corresponding piston bracing recess 1 22a is present in a proximal section of the piston body 1 20. The piston bracing recess 1 22a is realized as recess of a diameter slightly smaller than the bracing member 3 1 .

Fig 1 shows the dosing unit 3 in an initial state prior to its first use, with the active volume V not being filled with liquid and the configuration switch member 3 being in its storing position. The piston 1 2 is accordingly in its storing configuration. The dosing cylinder 1 1 and the piston 1 2, in particular the piston body 1 20 and the circumferential sealing member 1 21 , are dimensioned such that the contact of the circumferential outer surface of the circumferential sealing member 1 21 on the one hand and the circumferential inner wall of the dosing cylinder 1 1 , on the other hand , is loose. No or little mechanical stress is accordingly exerted onto the circumferential sealing member. In this state, no or only little sealing is present between the circumferential sealing member 1 21 and the dosing cylinder 1 2.

In the following, reference is additionally made to Fig. 2. Fig. 2 shows the dosing unit 1 in its operational configuration. For switching the piston 1 2 from the storing configuration as shown in Fig. 1 into the operational configuration as shown in Figure 2, the piston 1 2 is, together with the configuration switch member 3 , displaced along the displacement axis A in proximal direction. During this process, the proximal pin -shaped section of the configuration switch member body 30 is introduced into the proximal metering cavity recess 1 1 1 . Since the displacement of the plunger 1 2 and the configuration switch member 3 results in a decrease of the active volume V, the dosing cylinder aperture is favourably fluidic coupled with the outlet aperture, thus allowing initially present gas (typically air or an inert gas) to exit the dosing cylinder 1 1 . Upon the stop member front surface 32a contacting or hitting the metering cavity front wall 1 1 0a as blocking surface, the configuration switch member 3 is stopped and further displacement is prevented .

Further advancement of the piston 1 2 in proximal direction is accordingly associated with a displacement of the configuration switch member 3 in distal direction relative to the piston 1 2. The configuration switch member body 30 is accordingly further inserted into the configuration switch member recess 1 22, favourably under frictional force as explained above. Finally, the bracing member 3 1 is pressed into the piston bracing recess 1 22a. Since the piston bracing recess 1 22a has a somewhat smaller diameter than the bracing member 3 1 as explained before, a proximal section of the piston body 1 20 is radially braced outwards. Thereby, the circumferential sealing member 1 21 is pressed and biased against the circumferential inner wall of the dosing cylinder 1 1 , thus establishing fluid-tight sealing. Favourably, the piston body 1 20 is, at least in a proximal section, radial elastic, thus supporting the radial outwards bracing of the piston body 1 20. At its distal end ( pointing towards the piston body 1 20 ), the ring -shaped bracing member 3 1 is favourably chamfered ( not shown ) to support introduction into the piston bracing recess 1 22a.

In the following, reference is additionally made to Fig. 3 and Fig. 4, showing a further exem plary embodiment of a dosing unit 1 in accordance with the present disclosure. I n Fig. 3, the piston 1 2 is in the storing configuration, while it is in the operational configuration in Fig. 4. I n the following, only those elements and features are discussed that are different as compared to the previously discussed exem plary embodiment.

In the embodiment of Fig. 3 and Fig . 4, the piston 1 2 is a hollow tubular structure over its whole length. Proximal of the threaded piston recess 1 23 , a proximal piston recess 1 20 of smaller diameter is arranged . Proximal to the proximal piston recess 1 20, the config uration switch member recess 1 22 is arranged wh ich has a frustro-conical shape in this embodiment.

The circumferential sealing member 1 21 is arranged proximal and flush with the piston body 1 20 and engages the piston body 1 20 via positive locking. The configuration switch member recess 1 22 extends through the circumferential sealing member 1 21 in form of an axial through-hole of the circumferential sealing member 1 21 .

The configuration switch member 3 of this embodiment includes spring members in form of spring arms 34 and deflection protrusions 35 that are arranged at the distal ends of the spring arms 34 and point radially outwards. In the storing configuration as shown in Fig. 3, the spring arms 34 are radially deflected inwards from their un biased config uration by the deflection protrusions 35 contacting the inner circumferential wa ll of the configuration switch member recess 1 22. The spring arms 34 are accordingly radially biased. Simila r to the before-discussed em bodiment, switching from the storing configuration to the operational configuration is achieved by displacing the piston 1 2 in proximal direction while preventing displacement of the configuration switch member 3. At some point, the deflection protrusions 35 will exit the configuration switch member recess 1 22. The spring arms 34 will accordingly flex outwards, towards their unbiased configuration as shown in Fig. 4. The spring arms 34 flexing outwards causes a corresponding radial outwards flexing or bracing of the piston body 1 20 wh ich is favourably radial elastic. Thereby, the circumferential sealing member 1 21 is pressed and biased against the circumferential inner wall of the dosing cylinder 1 1 , thus establishing fluid-tight sealing. The before-discussed exem plary dosing units in accordance with the present disclosure may be modified and /or varied in a number of ways.

While hard plastics are typically used for the components of the dosing unit 1 (with exception of the circumferential sealing member 1 21 ), other materia ls such as ceramics, glass, or metal may also be used for some or all of the components alone or in com bination with other materials.

Furthermore, alternative drive arrangements may be used. In particular, rather than providing the threaded engagement between the drive sleeve 2 and the piston 1 2, a threaded engagement may be present between the piston 1 2 and the dosing cylinder 1 1 . In such embodiments, an electric drive un it and the dosing unit 1 may be operatively mechanically coupled by a rotational engagement for torque transmission, while enabling free sliding movement of the piston 1 2 relative to the drive sleeve 2 in axial direction. In still further embodiments, no threaded engagement is present and the piston 1 2 operatively couples to a linear displaceable plunger rod of the electric drive system. Furthermore, the valve switching for coupling the dosing cylinder aperture with the inlet aperture or outlet aperture may be realised in a different way. In particular, a functionally separate control valve may be provided for this purpose. In such embodiments, no rotation of the dosing cylinder 1 1 relative to the stationary member 1 0 is required. Furthermore, the stationary member 1 0 and the dosing cylinder 1 1 may be designed for axial rather than rotational sliding engagement. In such em bodiments, valve switching is achieved by axially displacing the dosing cylinder 1 1 relative to the stationary member 1 0.

Further locking means may be provided at the piston body 1 20 and /or the configuration switch member 3 for locking the configuration switch member 3 relative to the piston 1 2 in the operational position by force locking and /or positive locking.

It is to be generally noted that the technical realization of all aspects of the dosing unit that are unrelated to the engagement and sealing between piston and dosing cylinder is not essential. Therefore, the dosing units of the before-described exem plary embodiments are exem plary. In particular, the EP 1 970677, EP25 1 0962, EP25 1 0960, EP26969 1 5 , EP2457602, WO201 2/069308, WO201 3/029999 , EP2753380, EP21 63273 , EP2361 646 each disclose dosing units and/or systems including a dosing unit that may be modified in accordance with the present disclosure. As discussed before in the general description, the dosing unit may especially comprise or be realized as drug cartridge of generally known design and as widely used in infusion systems and devices, e.g. infusion pumps, of the syringe-driver type. Reference signs

A displacement axis

V liquid-filled volume of metering cavity

d Distal

p Proximal

I dosing unit

1 0 stationary part

I I dosing cylinder

1 1 0 distal metering cavity section

1 1 0a blocking surface / metering cavity front wall

I I I proximal metering cavity recess

1 2 piston / plunger

1 20 piston body

1 20a proximal piston recess

1 20b locking protrusion counter shoulder

1 21 circumferential sealing member

1 22 configuration switch member recess

1 22a piston bracing recess

1 23 threaded piston member / threaded piston recess

2 drive sleeve

20 threaded counter-member

3 configuration switch member

30 configuration switch member body

3 1 bracing member

32 stop member

32a stop member front surface

34 spring arm / spring member

35 locking protrusion