WO2017066887A1 - Device for administering an active substance and method for operating said device - Google Patents

Abstract

The invention relates to a device for administering an active substance, comprising: - a multi-chamber carpule (3) having a bypass (6) in one wall (7) of said multi-chamber carpule (3) and at least one first chamber (8) containing a solid active substance, and a second chamber (9) containing a solvent for said active substance, the second chamber (9) being delimited by a first plug (4) arranged distally in the multi-chamber carpule (3) and by a second plug (5) arranged proximally in the multi-chamber carpule (3); - a mixing device for mixing the active substance and the solvent, comprising a piston rod (2) wherein, when in a mixing process starting position, the second plug (5) is coupled to said piston rod (2) such that the second plug (2) can move back and forth, and a multi-chamber carpule retainer (1) for receiving said multi-chamber carpule (3); and - a first detent arrangement which is provided on the device such that, upon completion of the mixing process, axial displacement of a distal end of the second plug (5) relative to the wall (7) of the multi-chamber carpule (3) is blocked in the proximal direction by means of a distal end of the bypass (6).

Description

 Device for administering an active substance and method for operating this device

The invention relates to a device for administering an active substance and a method for operating this device. The device comprises a Mehitamrnerkarpule with a solid active ingredient and a dissolving liquid, and a mixing device for mixing the active ingredient and the Lösungsfiüssigkeit, wherein the mixing device comprises a piston rod.

Such a device serves to ensure that a liquid-unstable solid active substance can be mixed with a dissolving liquid only shortly before administration and is thus storable. Such devices, for example from WO2008 / 122132 A1 and WO2008 / 122360 A2, are known from the prior art.

Such a liquid-unstable solid active substance, which is mixed with a Lösungsfiüssigkeit shortly before administration, for example, is a recombinant coagulation factor in the form of a lyophilisate, which is used for the treatment of hemophilia

Hemophilia is a hereditary disease that leads to a disruption of blood clotting. The blood of affected patients does not clot or is delayed. This can also lead to spontaneous bleeding that occurs without visible wounds.

The therapy of patients with hemophilia is generally to substitute the missing or defective factor. The regular administration of coagulation factors ensures that their concentration does not fall below a critical value. For most patients, the occurrence of dangerous spontaneous reactions can thus be largely prevented. For therapy, the patients inject themselves regularly, for example, several times a week a certain amount of Gerrnnungsfaktoren in a vein.

As part of a Sifcstituttonstherapie patients with hemophilia A are injected about two to three times a week the missing coagulation factor VIII. Patients with hemophilia B require coagulation factor IX. After appropriate training, patients can administer the appropriate coagulation factors by means of a self-administering device.

In particular, when administering subscribed coagulation factors in the form of a lyophilizate, there is a challenge that, after dissolving the lyophilized coagulation factor in a dissolving fluid and piercing a cannula attached to an administering device of an infusion set into a patient's vein, aspiration of the venous Blood through the cannula of the infusion set, must be made possible. Through a transparent hose of the infusion set For example, the patient may recognize whether the hypodermic needle is in a vein, since aspiration shimmers the color of the aspirated venous blood through the clear tube.

Such devices are known from the prior art.

WO2013 / 149032 A1 describes a device for mixing lyophilized coagulation factors with a solution liquid and for administering the dissolved coagulation factors into a vein of a patient with hemophilia. During the mixing process, an atomizing device is moved in a distal direction of the administering device

WO2013 / 048877 A1 describes a device for administering an active substance, wherein the device for dispensing the active substance has a bendable piston rod.

EP7213S8 B1 describes a device for the administration of an active substance, wherein the bendable Kotbenstange is driven by a spindle drive.

A disadvantage of the above-mentioned devices is that after the mixing process of a solid drug with a Lösungsflüsskjkeit no safe and easy handling of the aspiration and the administration of the dissolved drug can be guaranteed.

It is therefore an object of the present invention to provide a device for administering an active ingredient which, after mixing a solid active substance with a solvent, ensures safe and easy handling of aspiration and administration of the dissolved active ingredient.

Furthermore, it is an object of the invention to provide a method of operating a device for administering an active substance ready for stetting, by which blending of a solid active substance with a liquid, aspirating and administering the dissolved active substance can be carried out safely and easily.

These objects are solved by the subject-matter of the independent claims. Pre-emptive execution orders are defined in the dependent claims.

In the following, distal means a direction toward the infusion set or dead end of the application device towards and proximal to the opposite end. The invention relates to a device for administering an active substance, which comprises a multi-chamber carpule with a bypass in a wall of the multi-chamber carpule and with at least a first chamber with a solid active substance and a second chamber with a solution liquid for the active substance. The second chamber is delimited by a first plug arranged distally in the multi-chamber carpule and a second plug arranged proximally in the multi-chamber carpule. The administering device comprises a mixing device for mixing the active substance and the dissolving liquid with a piston rod and a multi-chamber carpule holder for receiving the multi-chamber carpule. The piston rod is coupled to the second plug in an initial position of the blending operation such that upon reciprocal movement of the piston rod, the second plug is reciprocally movable. Further, a housing for receiving the mixing device is provided, wherein the multi-chamber carpule with the multi-chamber carpule for mixing the active substance and the solution liquid is rotatable relative to the housing in the housing. The mixing process can be done by screwing the multi-chamber carpule holder in the housing. For this purpose, the multi-chamber carpule holder comprises, for example, an external thread which can be in threaded engagement with an internal thread provided on the housing. The multi-chamber carpule accommodated by the multi-chamber carpule holder can be inserted into the housing by means of a combined axial and rotational movement. Alternatively, it is also possible to provide a purely axial mixing movement between the multi-chamber carpal holder and the housing. For this purpose, a longitudinal guide can be provided between the multi-chamber carpal holder and the housing.

Further, a first detent means may be provided on the delivery device such that upon completion of the blending operation, axial displacement of a distal end of the second plug relative to the wall of the multi-chamber carpule is blocked via a distal end of the bypass in the proximal direction. The first latching device serves to allow an axial relative movement between the second plug and the housing, in particular the wall of the multi-chamber carpule, only up to an aspiration stop position. The first latching device can ensure that the first and second plugs are always connected airtight to each other after the mixing process. On the other hand, it can be prevented that after the mixing process of the active substance with the dissolving liquid, air and / or the dissolved active substance can reach the area of the bypass of the multichamber carpule. Furthermore, the first latching device serves for a safe and easier administration of the dissolved active substance.

Particularly preferably, the first latching device can form a first detent position between the wall of the multi-chamber carpule and the piston rod. The first latching device can be designed as a stop device. The first latching device can be realized for example by a snap arm or latching arm on the piston rod, which can abut against a stop surface or recess or latching groove on the wall of the multi-chamber carpule to limit a relative axial movement between the piston rod and the wall of the multi-chamber carpule the Schnapparm or latching arm and the stop surface or recess or latching groove may be formed as an axial stop contact. The Schnapparm or latching arm may be arranged on the circumference of the piston rod. The snap arm or latching arm may extend along the longitudinal axis and be radially biased radially, in particular elastically radially. Alternatively, the wall of the multi-chamber carpule the Schnapparm or latching arm and the piston rod, the stop surface or recess or latching groove. Alternatively, a plurality of snap arms, latching arms, stop surfaces, recesses or latching grooves may be provided in each case.

Further, a second latching device is provided on the device such that during the mixing of the active substance and the solution liquid, an axial displacement or a screw movement of the Mehrkam merkarpulenhalters is prevented relative to the housing in the distal direction. The second locking device can serve the safe mixing of the solid active substance with the dissolution liquid, since a mixing movement in the direction opposite to the mixing direction is prevented. A started mixing process can not be undone. Furthermore, the second locking device may comprise a display device, wherein the display may be given by an acoustically perceptible detent sound. The second latching device may preferably form a second detent position between the housing and the multi-chamber carousel hatcher. For this purpose, for example, a Schnapparm or latching arm may be provided on the Mehrkammerkarpulenhalter which can abut against a stop surface or recess or latching groove on the housing in order to limit a relative axial movement between the Mehrkammer- carpule holder and the housing. The stop contact between the Schnapparm or latching arm and the stop surface or recess or latching groove may be formed as a radial stop contact, the Schnapparm or latching arm may be arranged on the circumference of the multi-chamber carpule holder. The snap arm or latch arm may extend along a circumferential direction and be radially biased radially, in particular elastically. Alternatively, the housing may have the snap arm or latching arm and the multi-chamber carpule holder the stop surface or recess or Rastriile. Alternatively, several Schnapparme, latching arms, stop surfaces, recesses or Rastrilien can be provided in each case.

Particularly preferably, the administration device can comprise one or more second latching devices and / or display devices which ensure and / or display different positions, in particular the relative position between the multi-chamber carpule holder and the housing during the mixing process. By the movement of the multi-chamber carpule holder relative to the housing, first a second detent position and / or display in the delivery position, then the blending position and finally the end position of the priming, the venting position, ensured or displayed, Furthermore, the display device as a visual, tactile or acoustic display be educated. Particularly preferably, the piston rod in the delivery position of the active ingredient and the solution liquid may be spaced from the second stopper and axially fixed to the second stopper in the initial position of the mixing position of the active ingredient and the dissolving liquid. For this purpose, a thread, in particular an external thread on the piston rod and a mating thread, in particular an internal thread on the plug can be used, which can be brought into a threaded engagement. The second plug can also be latched to the piston rod, for example via a Verrasterungsmechanismus such that the second plug with the piston rod axially fixed and preferably rotatably connected. Alternatively, other positive or alternatively non-positive axially fixed connections between the piston rod and the stopper may be provided.

An actuator may be attached to the proximal end of the piston rod. The piston rod is at least partially received by the actuator. The actuating element is arranged axially movable relative to the piston rod. The actuating element can be axially fixed and preferably non-rotatably connected via a first holding device to the piston rod and be axially movable after releasing the first holding device relative to the piston rod. The actuating element is located in a distal position relative to the piston rod when the actuating element via the first holding means with the piston rod axially fixed and preferably non-rotatably connected. The holding connection between the actuating element and the piston rod can be released either by inserting the multi-chamber carpule holder, in particular by a proximal end or by a proximal edge of the multi-chamber carpule holder, wherein the actuating element is pulled by hand from the administering device in the proximal direction may or alternatively may be pushed from the multi-chamber carpal len holder, in particular the proximal end or the proximal edge of the multi-chamber carpule from the administering device in the proximal direction. Consequently, in the end position of the mixing process or after the priming operation, a release button attached to the proximal end of the piston rod can protrude out of the housing. Alternatively, in the end position of the mixing process or after the priming process, an actuating element attached to the proximal end of the piston rod can be pulled out of the housing. The actuator may be configured such that the patient can axially slide the actuator back and forth with a finger.

After the actuating element has moved out of the housing, the actuating element can enter into a axiatfeste and preferably rotationally fixed connection with the piston rod via a second holding device. The actuating element is located in a proximal position relative to the piston rod when the actuating element is connected to the piston rod via the second holding device axially fixed and preferably non-rotatably. The actuator may be connected to the second plug via the piston rod such that upon axial reciprocation of the actuator relative to the housing, the second plug is reciprocable relative to the wall of the multi-chamber carpule. The invention will be described below with reference to several figures. The features disclosed herein further advantageously form the invention. Show it:

Figure 1 a; a longitudinal sectional view of the first embodiment of a Verabreichungsvom ^'rect in a delivery position of a Mehrkam merkarpulenhalters (1)

 FIG. 1b is a longitudinal sectional view of the first embodiment of the administering device in an initial position of the mixing position of the multi-chamber carpal holder (1).

 1c is a longitudinal sectional view of the first embodiment of the administering device in an end position of the mixing position of the multi-chamber carpule holder (1)

FIG. 1 d is a longitudinal sectional view of the first embodiment of the administering device in a priming position of the multi-chamber carpule holder (1)

 Figure 1e is a longitudinal sectional view of the first embodiment of the administering device in an aspiration stop position

 Figure 1f is a longitudinal sectional view of the first embodiment of the administering device in a dispensing position

FIG. 1a shows a longitudinal sectional view of a first embodiment of the administering device in a delivery position of the multi-chamber carpule holder (1). A multi-chamber carpule (3) is received by a multi-chamber carpule holder (1). In a second chamber (9) of the multi-chamber carpule (3), the dissolving liquid and in the first chamber (8) of the multi-chamber carpule (3) of the solid active substance is received, wherein the second chamber by a in the multi-chamber carpule (3) distally arranged first (4 ) and in the multi-chamber carpule (3) proximally arranged second plug (5) is limited. In a wall (7) of the multi-chamber carpule (3), a bypass is provided. The first plug (4) is arranged offset proximally to the bypass (6). The multi-chamber carpule holder (1) and the housing (10) are threadedly engaged via an external thread (1a) of the multichamber carpule holder (1) and an internal thread (10a) of the housing. An actuating element (11) is provided at the proximal end of the housing (10) and a piston rod (2) is provided inside the housing (10). The actuating element (11) is connected via a first holding device with the piston rod (2) axiaifest and preferably rotatably connected. The connection between the actuating element (11) and the piston rod (2) is detachably formed. The piston rod (2) accommodated in the housing (10) is held axially fixed by means of a detachable retaining connection relative to the housing (10).

FIG. 1b is a longitudinal sectional view of the first embodiment of the administering device of FIG. 1b in an initial position of the blending position of the multichamber carpule holder (1). On the distal At the end of the delivery device, an infusion set or other device can be placed with a cannula. The multi-chamber carpule holder (1) accommodated with the multi-chamber carpule (3) is threadedly rotated into the housing (10) relative to the housing (10) and thus moved in the proximal direction. The multi-chamber carpule holder (1) is screwed into the housing (10). By introducing the multi-chamber carpule (1) in the housing (10) comes the Außenge thread (2 a) of the piston rod (2) in a threaded engagement with the internal thread (5 a) of the second plug (5). The second plug (5) is axially fixed to the piston rod and preferably rotatably connected.

FIG. 1c shows a longitudinal sectional view of the first embodiment of the administering device in an end position of the mixing position of the multichamber carpule holder (1). Continuing the insertion movement pushes the piston rod (2) the second plug (5) relative to the wall (7) of the multi-chamber carpule (3) in the distal direction. The driving force is thereby first transferred to the first plug (4) by the dissolving liquid in the second chamber (9) so that both plugs (4, 5) are driven distally. As soon as the first plug (4) comes to lie in the region of the bypass (6), the first plug (4) remains at rest relative to the wall (7) of the multi-chamber carpule (3). The second plug (5) is further driven, so that the solution liquid from the second chamber (9) via the bypass (6) in the first chamber (4) passes and can solve the drug located there. The second plug (5) is driven until it hits the first plug (4). Thereby, the end position of the mixing position of the administering device is achieved. The actuating element (11) can be pushed out of the housing (10) relative to the housing (10) or the piston rod (2) in the proximal direction by the proximal end of the multi-chamber carpule (1) or the proximal edge of the multi-chamber carpule (1). In another embodiment, in the final position of the blending position, a patient may manually pull the actuator (11) relative to the housing (10) or piston rod (2) in the proximal direction. After the actuating element has been moved out of the housing or pulled, or is in a proximal position, the actuating element (11) with the piston rod (2) via a second holding means an axially fixed and preferably rotatable connection received.

FIG. 1d shows a longitudinal sectional view of the first embodiment of the administering device in a priming position of the multi-chamber carpule holder (1). By actuating the actuating element (11), in particular by a movement of the actuating element (11) in the distal direction, the first (4) and second plug (5) are moved in the distal direction. Therefore, superfluous air can escape from the first chamber (8) through the infusion set or the other device with a cannula.

FIG. 1e shows a longitudinal sectional view of the first embodiment of the administering device in an aspiration stop position. After the actuating element (11) is moved out of the housing (10), or in a proximal position, the actuating element (11) with the Piston rod (2) via a second holding device (not shown) enter into an axially fixed and preferably rotationally fixed connection. The actuating element (11) can be connected to the second plug (5) via the piston rod (2) in such a way that the second plug can be moved back and forth relative to the wall of the multi-chamber carpule with axial reciprocation of the actuating element relative to the housing is. The administering device comprises a first latching device (not shown) which is designed so that after completion of the blending operation an axial displacement of a distal end of the second plug (5) relative to the wall (7) of the multi-chamber carpule (3) via a distal end of the bypass (6) is blocked in the proximal direction. This position defines the aspiration stop position. The first latching device can, for example, by a latching arm (not shown) on the piston rod

(2) which is connected to a latching groove (not visible) on the wall (7) of the multi-chamber carpule

(3) or the housing (10) or the multi-chamber carpule holder (1) can strike to limit a relative axial movement between the piston rod (2) and the multi-chamber carpule (3). The latching arm may in particular be radially outwardly biased so that it slides along the wall (7) of the multi-chamber carpule (3) or the housing (10) or the Mehrkammerkarpulenhalters (1) during the axial movement, until the locking arm due to its shape, for example locked as a pawl or hook with the latching groove. A relative axial movement of the piston rod (2) or of the actuating element (11) in the proximal direction can thus be carried out only up to the aspiration stop position. The piston rod (2) or actuator (11) can be reciprocated between the aspiration stop position and, preferably, prior to reaching the dispensing position relative to the housing (10). The relative reciprocation between the piston rod (2) or the actuator (11) and the housing (10) is intended to be such that the patient can control whether the infusion set or the other device has a cannula for administering the solute stuck in the vein. After this inspection or after several such controls, or after these relative reciprocations or several of these reciprocations, the patient further moves the piston rod (2) or actuator (11) in the proximal direction to the dispensing position as in the figure 1fe is reached is reached. The movement of the actuating element (11) is transmitted via the piston rod (2) to the first (4) and the second plug (5), so that the mixed active substance is released from the first chamber (8).

Preferably, a second latching and / or display device (not shown) for latching and / or displaying the individual preparation steps of the administering device can be provided on the administration device. The locking can be designed as reverse rotation. The latching and / or display device comprises at least one latching groove or recess, for example a latching opening, which can interact with at least one latching arm. For example, the latching arm may be provided on the multi-chamber carpule holder (1), which in at least one latching groove or in at least one output. can abut the housing (10) or a housing-fixed part in order to limit a relative axial movement between the housing (10) and the Metirkammerkarpulenhalter (1) in the distal direction. The latching may preferably generate an audible signal which may indicate the achievement of a corresponding position. The latching arm is designed in such a way that, due to its prestressing and shaping, it blocks, for example as a pawl or hook, rewinding or reversing of the multichamber carput holder (1) relative to the housing (10) by a stop on the latching groove or recess It is therefore only possible to move the multi-chamber coil holder (1) further in the proximal direction It is basically possible to arrange the first detent groove over the length of the housing (10) in such a way that after each revolution of the multi-chamber coiled rod holder (1) From the delivery position, the multi-chamber carpule holder (1) is further locked in the proximal direction until, for example, it locks in a further latching groove with the latching arm, whereby the termination of mixing and / or priming and / or emptying the multi-chamber carpule (3) can be displayed Alternatively or in addition to the audible indication, a visual and / or tactile indication and / or a further audible indication may be provided on the delivery device.

Reference numerals;

Claims

claims 1. Device for administering an active substance comprising  a multi-chamber carpule {3} with a bypass (6) in a wall (7) of the multi-chamber carpule (3) and with at least one first chamber (8) with a solid active substance and a second chamber (9) with a solvent liquid for the active substance, wherein the second chamber (9) is delimited by a first plug (4) arranged distally in the multichamber carpule (3) and a second plug (5) arranged proximally in the multichamber carpule (3),  a mixing device for mixing the active substance and the solution liquid comprising a piston rod (2), wherein in an initial position of the mixing process, the second plug (5) is coupled to the piston rod (2) such that upon a reciprocating movement of the piston rod (2 ) the second plug (5) is movable back and forth, and a multi-chamber carpule holder (1) for receiving the multi-chamber carpule (3),  a housing (10) for receiving the mixing device,  wherein the multi-chamber carpule holder (1> with the multi-chamber carpule (3) accommodated therein for mixing the active substance and the dissolving liquid is rotatable relative to the housing (10) into the housing (10),  characterized in that a first latching device is provided on the device such that upon completion of the blending operation, axial displacement of a distal end of the second plug (5) relative to the wall (7) of the multi-chamber carpule (3) via a distal end of the bypass (6) is blocked in the proximal direction. 2. Apparatus according to claim 1, characterized in that the first latching device forms a first detent position between the wall (7) of the multi-chamber carpule (3) and the piston rod (2). 3. Device according to one of the preceding claims, characterized in that a second locking device is provided on the device such that during the mixing of the active substance and the solution liquid, an axial displacement of the multi-chamber carpule holder (1) relative to the housing (10) in the distal Direction is prevented. 4. Apparatus according to claim 3, characterized in that the second latching device forms a second detent position between the housing (10) and the multi-chamber carpule holder (1). 5. Device according to one of the preceding claims, characterized in that the piston rod (2) in a delivery position of the active ingredient and the dissolving liquid spaced from the second Plug (5) is arranged and in the initial position of the mixing of the active ingredient and the solution liquid axially fixed, in particular axially fixed and rotationally fixed to the second plug (5) is connected. 6. Apparatus according to claim 5, characterized in that a thread, in particular an external thread (2a) on the piston rod (2) and a mating thread, in particular an internal thread (5a) on the second plug (5) is used, which in a threaded engagement can be brought. 7. Device according to one of the preceding claims, characterized in that in an end position of the mixing process or after a priming operation at the proximal end of the piston rod (2) mounted actuating member (11) protrudes from the housing (10) in the proximal direction. 8. Device according to one of the preceding claims, characterized in that in an end position mixing process or after a priming operation at the proximal end of the piston rod (2) attached actuating element (11) from the housing (10) in the proximal direction can be pulled out. 9. Apparatus according to claim 7 or 8, characterized in that the actuating element (11) via the piston rod (2) with the second plug (5) is connected, that at an axial reciprocating movement of the actuating element (11) relative to the housing (10) of the second plug (5) relative to the wall (7) of the multi-chamber carpule (3) is movable back and forth. 10. Device according to one of claims 7 to 9, characterized in that the piston rod (2) is at least partially received by the actuating element (11). 11. Method for operating a device according to one of the preceding claims, characterized by the following steps:  Rotation of the multi-chamber carpule holder (1) with the multichamber carpule (3) accommodated therein, relative to and into a housing (10)  Mixing a solid active substance with a solution liquid for the active substance in a multi-chamber carpule (3), wherein the multi-chamber carpule (3) has a bypass (6) in a wall (7) of the multi-chamber carpule (3), at least one first chamber (8) with a solid active substance and a second chamber (9) with a dissolving liquid for the active substance, wherein the second chamber (9) is arranged distally in the multichamber carpule (3) ) and in the multi-chamber carpule (3) proximally arranged second plug (5) is limited Coupling a piston rod (2) with the second plug (5) such that during a reciprocating movement of the piston rod (2), the second plug (5) is movable back and forth Blocking an axial displacement of a distal end of the second plug (5) relative to the wall (7) of the multi-chamber carpule (3) via a distal end of the bypass (7) in the proximal direction after the blending operation. 12. The method according to claim 11, characterized in that during the axial movement, in particular the combined rotational and axial movement of the Mehrkammerkarpulenhalters (1) with the multichamber Karpule (3) received therein relative to and in the housing (10) of the second plug (5 ) with the piston rod (2) coupled. 13. The method according to claim 11 or claim 12, characterized in that during the mixing process or during a priming operation at the proximal end of the piston rod (2) provided actuating element (11) relative to the piston rod (2) moves in the proximal direction. 14. The method according to claim 11 or 12, characterized in that in an end position of the mixing process or after a priming an attached to the proximal end of the piston rod (2) actuating element (11) pulled out of the housing (10) in the proximal direction becomes. 15. The method according to claim 13 or 14, characterized in that the actuating element (11) in a proximal position an axially fixed, in particular an axially fixed and rotationally fixed connection with the piston rod (2) received. 16. The method according to claim 15, characterized in that a reciprocating movement of the Betätigungsseiements (11) causes a reciprocating movement of the second plug (5).