DRUG RESERVOIR FOR SEPARATE STORAGE OF SUBSTANCES

Abstract

The present invention provides a drug reservoir (1) comprising a reservoir body (2) extending between an outlet end (4) and a proximal end (7), a front piston (8) arranged in a pre-use position within the reservoir body (2) between the outlet end (4) and the proximal end (7), a rear piston (9) arranged within the reservoir body (2) between the front piston (8) and the proximal end (7) a distal chamber (10) defined by the outlet end (4), a first portion of the reservoir body (2), and the front piston (8), the distal chamber (10) holding first contents (18), a proximal chamber (11) defined by the front piston (8), a second portion of the reservoir body (2), and the rear piston (9), the proximal chamber (11) holding second contents (12, 19) comprising a proximal liquid volume (19), and bypass means (3) allowing fluid flow past the front piston (8) in an advanced position of the front piston (8) in the reservoir body (2), wherein the second contents (12, 19) further comprises a proximal gas volume (12) lying within a volume range having a predetermined minimum value.

Claims

1. A drug reservoir comprising: a reservoir body extending between an outlet end and a proximal end, a front piston arranged in a pre-use position within the reservoir body between the outlet end and the proximal end, a rear piston arranged within the reservoir body between the front piston and the proximal end, a distal chamber defined by the outlet end, a first portion of the reservoir body, and the front piston, the distal chamber holding first contents, a proximal chamber defined by the front piston, a second portion of the reservoir body, and the rear piston, the proximal chamber holding second contents comprising a proximal liquid volume, and a bypass structure allowing fluid flow past the front piston in an advanced position of the front piston in the reservoir body, wherein the second contents further comprises a proximal gas volume lying within a volume range having a predetermined minimum value.

2. The drug reservoir according to claim 1, wherein the predetermined minimum value is 15 μl.

3. The drug reservoir according to claim 1, wherein the volume range is a predetermined closed volume range.

4. The drug reservoir according to claim 3, wherein the predetermined closed volume range is 15 μl to 200 μl.

5. The A drug reservoir according to claim 3, wherein the predetermined closed volume range is 20 μl to 50 μl.

6. The drug reservoir according to claim 1, wherein the first contents comprises a distal liquid volume and a distal gas volume, and wherein the distal gas volume is smaller than the proximal gas volume.

7. The drug reservoir according to any of the preceding claim 1, wherein the proximal gas volume comprises air.

8. The drug reservoir according to claim 1, wherein the proximal gas volume comprises an inert gas.

9. The drug reservoir according to claim 1, further comprising a hollow needle fixedly arranged at the outlet end and fluidly connected with the distal chamber.

10. A drug delivery device comprising: a drug reservoir according to claim 1, and a dose expelling structure for pressurising the proximal chamber, the dose expelling structure comprising an actuatable piston rod adapted to transfer an expelling force to the rear piston.

11. The drug delivery device according to claim 10, further comprising a housing extending along a reference axis, wherein the dose expelling structure is powered by a spring member operatively coupled with the piston rod and adapted to store energy releasable to urge the piston rod towards the outlet end.

12. The drug delivery device according to claim 11, further comprising: a retention structure which when enabled retains the spring member in a tensioned state, and a sleeve member extending axially along a portion of the housing and comprising a release structure, wherein the sleeve member is configured for proximal displacement relative to the housing and the retention structure from a first position in which the retention structure is enabled to a second position in which the retention structure is disabled by the release structure and stored energy consequently is released from the spring member.

13. A method of filling a drug reservoir comprising a generally cylindrical main body with a bypass section, a closed outlet end, and an open end, the method comprising: (i) arranging the drug reservoir at least substantially vertically with the open end facing upward, (ii) introducing a first liquid volume into the drug reservoir through the open end such that a first interior portion of the generally cylindrical main body, including the bypass section, is covered by liquid in a vertical position of the drug reservoir where the open end faces upward, (iii) in a first sub-atmospheric pressure environment inserting a first piston into the generally cylindrical main body to a first piston position at least substantially adjoining the free surface of the first liquid volume, thereby establishing a front chamber holding the first liquid volume, (iv) introducing a second liquid volume into the drug reservoir through the open end, and (v) in a second sub-atmospheric pressure environment of a surrounding gas inserting a second piston into the generally cylindrical main body to a second piston position, thereby establishing a rear chamber, where the second piston position is determined such that the rear chamber holds the second liquid volume and a rear chamber gas volume lying within a volume range having a predetermined minimum value.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0049] In the following the invention will be further described with references to the drawings, wherein

[0050] FIG. 1 is a longitudinal section view of a drug reservoir according to an exemplary embodiment of the invention in a pre-use state,

[0051] FIGS. 2a-2c are graphs showing an initial force application to the rear reservoir piston in cases without a proximal gas volume, respectively with two different proximal gas volumes,

[0052] FIG. 3 is a principle sketch of the process for filling the drug reservoir with two liquid volumes,

[0053] FIG. 4 is a longitudinal section view of an exemplary drug delivery device employing the drug reservoir of FIG. 1,

[0054] FIG. 5 is a longitudinal section view of the drug delivery device in a ready to use state,

[0055] FIGS. 6-10 are longitudinal section views of the drug delivery device in different in-use states, and

[0056] FIG. 11 is a longitudinal section view of the drug delivery device in a post use, emptied state.

[0057] In the figures like structures are mainly identified by like reference numerals.

DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0058] When/If relative expressions, such as “upper” and “lower”, “left” and “right”, “horizontal” and “vertical”, “clockwise” and “counter-clockwise”, etc., are used in the following, these refer to the appended figures and not necessarily to an actual situation of use. The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only.

[0059] FIG. 1 is a longitudinal section view of a drug reservoir 1 according to an exemplary embodiment of the invention. The drug reservoir 1 is depicted in a pre-use state, i.e. in a state as supplied by the manufacturer (albeit without a rigid needle protector).

[0060] The drug reservoir 1 has a generally cylindrical reservoir body 2 with a bypass channel 3 and a narrowed distal end portion 4. An injection needle 5 is fixed to the distal end portion 4 and establishes fluid communication to a reservoir outlet 6. A front piston 8 is arranged in the reservoir body 2 between the reservoir outlet 6 and an open proximal end 7, and a front chamber 10 is thereby defined by the reservoir outlet 6, a front portion of the reservoir body 2 comprising the bypass channel 3, and the front piston 8. A rear piston 9 is arranged in the reservoir body 2 between the front piston 8 and the open proximal end 7, and a rear chamber 11 is thereby defined by the front piston 8, a middle portion of the reservoir body 2, and the rear piston 9. The rear piston 9 has a cavity 13 adapted to receive an end portion of a piston rod (not shown).

[0061] The front chamber 10 holds a first liquid substance 18, and the rear chamber 11 holds a second liquid substance 19 as well as a proximal gas volume 12, sketched in the form of a gas bubble in the liquid drug 19. The proximal gas volume 12 is deliberately introduced in the rear chamber 11 in order to reduce the force required to perform an expelling of the reservoir contents through the injection needle 5, as will be described in further detail below. In the present example the proximal gas volume is 15 μl.

[0062] If a piston rod is inserted into the cavity 13 and a distally directed force is applied to the rear piston 9 the rear piston 9 will stay in its initial position until the applied force exceeds a certain threshold required to overcome the static friction in the contact interface between the sealing exterior surface of the rear piston 9 and the inner wall of the reservoir body 2.

[0063] FIGS. 2a-2c indicate the initial force required to set the rear piston 9 into motion in three different cases, where the graph in FIG. 2a is the force profile for a drug reservoir without a proximal gas volume, the graph in FIG. 2b is the force profile for a drug reservoir with a proximal gas volume of 15 μl, and the graph in FIG. 2c is the force profile for a drug reservoir with a proximal gas volume of 20 μl.

[0064] In a dual chamber drug reservoir without a proximal gas volume in the rear chamber the liquid acts as a rigid connection between the front piston and the rear piston. The single force peak, F.sub.0, in FIG. 2a reflects the fact that, in such a device, in order to set the rear piston into motion the front piston needs to be set into motion also, due to the incompressibility of the liquid. According to the present experiments a break loose force of approximately 15N is required to overcome the static friction in the system comprising both pistons.

[0065] In contrast thereto, as the graph in FIG. 2b shows, when a predetermined proximal gas volume of 15 μl is present in the rear chamber 11 the gas will add some flexibility to the system which will result in the rear piston 9 breaking loose before the front piston 8. A smaller force, F.sub.r,15, just short of 7N is required in this case to set the rear piston 9 into motion, as the proximal gas volume is compressed. The force rises subsequently, as the gas becomes fully compressed and the liquid/gas system consequently acts as a rigid connection between the two pistons, until the front piston 8 breaks loose at a next force peak, F.sub.f,15, around 11N. A sudden drop in the force level following the breaking loose of the front piston 8 reflects the transition from static friction to kinetic friction between the pistons and the inner reservoir wall. As the liquid in the front chamber 10 is pressurised and forced out through the small lumen of the injection needle 5 at a continued motion of the front piston 8, the force again increases some, due to the flow resistance in the injection needle 5, but does not approach the level of F.sub.0.

[0066] In FIG. 2c the difference is even more pronounced. Depicting results of experiments with a proximal gas volume of 20 μl in the rear chamber 11, the graph reveals a comparable force, F.sub.r,20, for breaking loose the rear piston 9 but a significantly smaller force, F.sub.f,20, in the area of 9N, for subsequently breaking loose the front piston 8. All in all, as the graphs indicate, when a proximal gas volume of at least 15 μl is present in the rear chamber 11 the required maximum force for initiating and carrying through a drug expelling action is reduced because the flexibility provided by said gas volume enables the rear piston 9 to break loose from the reservoir wall separately from the front piston 8.

[0067] FIG. 3 is a principle sketch of the process for filling the drug reservoir 1 with two liquid volumes. From left to right the process steps include holding the drug reservoir 1 in an upright position with the injection needle 5 sealed up by a needle plug 41 and introducing a predetermined volume of the first liquid substance 18 into the reservoir body 2 through the proximal end 7.

[0068] Having filled a distal portion of the reservoir body 2 to a level where the bypass channel 3 is covered the drug reservoir 1 is placed in a first sub-atmospheric pressure environment 100. The front piston 8 is arranged in a radially compressed state in an insertion tube 80 having an inner diameter which is smaller than the inner diameter of the reservoir body 2, and the insertion tube 80 is introduced into the reservoir body 2 through the proximal end 7, notably without touching the inner wall of the reservoir body 2. The front piston 8 is then pushed through the insertion tube 80 and expands into contact with the inner wall of reservoir body 2 just above the free surface of the first liquid substance 18, thereby establishing the front chamber 10, and the drug reservoir 1 is subsequently re-exposed to normalised pressure conditions. The negative pressure in the front chamber 10 due to the front piston 8 being inserted in the first sub-atmospheric pressure environment 100 will cause the front piston 8 to move towards the first liquid substance 18, closing any gap to the free surface thereof.

[0069] A predetermined volume of the second liquid substance 19 is introduced into the reservoir body 2 though the proximal end 7 and fills a space above the front piston 8. The drug reservoir 1 is then placed in a second sub-atmospheric pressure environment 200 of a surrounding gas, and the insertion tube 80, now carrying the rear piston 9 in a radially compressed state, is introduced into the reservoir body 2 in a manner similar to the above described. This time the pressure is controlled such that when the rear piston 9 is deposited in the reservoir body 2, thereby establishing the rear chamber 11, and the drug reservoir 1 is subsequently re-exposed to normalised pressure conditions a volume of the surrounding gas remains in the rear chamber 11 as a free gas volume lying within a volume range having a predetermined minimum value.

[0070] FIG. 4 is a longitudinal section view of the drug reservoir 1 forming part of an exemplary, dedicated auto-injector 20. The auto-injector 20 comprises a tubular housing 21 closed proximally by a transversal end wall 22 and accommodating a drug expelling mechanism including a piston rod 30 having a head portion 31 inserted into the cavity 13 and a shoulder portion 32 adapted to apply a distally directed force to the rear piston 9.

[0071] A couple of snap arms 24 extend distally from the transversal end wall 22 into the interior of the housing 21, ending in respective claws 26 with “v”-shaped interfacing portions 27 configured for engagement with corresponding depressions 33 in the piston rod 30. Each snap arm 24 has a proximal carving 25 which provides flexibility and allows for radial deflection of the claw 26.

[0072] A pre-tensioned compression spring 65 is arranged within the piston rod 30 and supported proximally by a central pin 23 which extends distally from the transversal end wall 22. The spring 65 is adapted to act between a distal end portion of the piston rod 30 and the transversal end wall 22.

[0073] The drug reservoir 1 is held within the housing 21 and is closed distally by a rigid needle protector 40 carrying the needle plug 41. An elongated sleeve 50 is arranged concentrically with, and between, the drug reservoir 1 and the housing 21. The sleeve 50 is axially displaceable relative to the housing 21, biased in the proximal direction by a sleeve spring 75, and comprises a radially enlarged proximal end portion 51 with a narrow adjoining section 53. In the shown pre-use state of the auto-injector 20 the sleeve 50 is in its maximum extended position relative to the housing 21, and the proximal end portion 51 is axially aligned with the claws 26, physically preventing the interfacing portions 27 from leaving the depressions 33. The auto-injector 20 is thus safely cocked, as the spring 65 is maintained in its pretensioned state because the piston rod 30 is unable to undergo axial motion relative to the housing 21.

[0074] FIG. 5 is a longitudinal section view of the auto-injector 20 in a ready-to-use state, after removal of the rigid needle protector 40 and the needle plug 41. The sleeve 50 is still in its maximum extended position relative to the housing 21, where a distal sleeve end portion 52 covers the injection needle 5 and thus protects the user from accidental needle stick injuries.

[0075] The distal sleeve end portion 52 has a sleeve rim 54 adapted to abut, and be pressed against, the user's skin at the desired injection site during drug expelling.

[0076] FIGS. 6-11 illustrate in a step-wise manner the dose expelling sequence of the auto-injector 20. Firstly, the user places the sleeve rim 54 in contact with a desired skin location (not shown) and presses the housing 21 against the skin. This causes the distal sleeve end portion 52 to compress the sleeve spring 75, as the housing 21 and the sleeve 50 undergo relative axial motion from the mutual position shown in FIG. 5 to that shown in FIG. 6. In essence the sleeve 50 is displaced proximally relative to the housing 21 and this causes the respective enlarged proximal end portions 51 to slide proximally along the claws 26. At some point, when the distal sleeve end portion 52 is pressed back sufficiently far that the tip of the injection needle 5 is exposed and has penetrated the skin surface, the sleeve 50 reaches a position relative to the snap arms 24 in which the enlarged proximal end portions 51 are no longer axially aligned with the claws 26. Instead, the claws 26 are axially aligned with the narrow adjoining section 53 and thereby no longer prevented from radial displacement.

[0077] The pre-tensioned spring 65 constantly provides a distally directed bias to the piston rod 30, so when the claws 26 are no longer radially fixated the axial force from the spring 65 and the respective configurations of the interfacing portions 27 and the depressions 33 will cause the snap arms 24 to deflect radially about the proximal carvings 25, leading to a disengagement of the claws 26 from the piston rod 30 and a resultant release of the spring 65. This is indicated in FIG. 7.

[0078] The initial result of the release of the spring 65 is also seen in FIG. 7. The presence of the proximal gas volume 12 enables a small compression of the rear chamber 11, so as the force from the expanding spring 65 pushes the piston rod 30 forward the rear piston 9 breaks loose from the inner wall of the reservoir body 2 while the front piston 8 remains stationary, the spring 65 at this point thus having to overcome only the static friction between the rear piston 9 and the reservoir body 2 (and not also the static friction between the front piston 8 and the reservoir body 2). In FIG. 7 the compression of the rear chamber 11 is illustrated by a reduced size of the proximal gas volume 12.

[0079] When the proximal gas volume 12 is fully compressed the contents of the rear chamber 11 will transfer the force from the spring 65 to the front piston 8 which will then break loose and move distally in the reservoir body 2 along with the rear piston 9, the second liquid substance 19 and the compressed proximal gas volume. The rear chamber 11 as such is thus displaced within the reservoir body 2, while a volume of the first liquid substance 18 is forced out through the injection needle 5, until the front piston 8 reaches the bypass channel 3, as shown in FIG. 8, at which point the second liquid substance 19 is forced into the bypass channel 3 and past the front piston 8 as the spring 65 keeps expanding.

[0080] The rear chamber 11 eventually collapses as the rear piston 9 approaches the front piston 8 and the second liquid substance 19 is transferred to the front chamber 10 where it mixes with the remains of the first liquid substance 18. FIG. 9 depicts the state of the auto-injector 20 immediately after the collapse of the rear chamber 11.

[0081] The mixed first liquid substance 18 and second liquid substance 19 is now expelled from the front chamber 10 through the injection needle 5 as the rear piston 9, under the influence of the piston rod 30 and the spring 65, pushes the front piston 8 further distally in the reservoir body 2. In FIG. 10 the front piston 8 covers the distal end of the bypass channel 3 and thus seals off the front chamber 10 in the proximal direction.

[0082] The drug expelling continues until the front piston 8 reaches a constriction of the reservoir body 2 at the reservoir outlet 6, after which the injection needle 5 is pulled out of the skin by the user moving the housing 21 away from the injection site. As the pressure between the skin surface and the sleeve rim 74 is relieved the sleeve spring 75 expands and urges the sleeve 50 distally relative to the housing 21 until the distal sleeve end portion 52 again covers the injection needle 5. The auto-injector 20 is now in a post-use state, as shown in FIG. 11, and may be discarded safely with no risk of accidental needle stick injuries.