WO2006045528A1 - Injection device with torsion spring and rotatable display - Google Patents

Injection device with torsion spring and rotatable display Download PDF

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Publication number
WO2006045528A1
WO2006045528A1 PCT/EP2005/011287 EP2005011287W WO2006045528A1 WO 2006045528 A1 WO2006045528 A1 WO 2006045528A1 EP 2005011287 W EP2005011287 W EP 2005011287W WO 2006045528 A1 WO2006045528 A1 WO 2006045528A1
Authority
WO
WIPO (PCT)
Prior art keywords
dose
injection device
piston rod
dose setting
setting member
Prior art date
Application number
PCT/EP2005/011287
Other languages
French (fr)
Inventor
Claus Schmidt Moller
Tom Hede Markussen
Christian Peter Enggaard
Original Assignee
Novo Nordisk A/S
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34928585&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2006045528(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to DE602005017182T priority Critical patent/DE602005017182D1/en
Priority to JP2007537215A priority patent/JP5185620B2/en
Priority to CN2005800396135A priority patent/CN101084028B/en
Priority to DK05796880.2T priority patent/DK1819382T3/en
Priority to AU2005298946A priority patent/AU2005298946B2/en
Priority to AT05796880T priority patent/ATE445430T1/en
Priority to US11/665,571 priority patent/US8357120B2/en
Priority to CA2584762A priority patent/CA2584762C/en
Priority to PL05796880T priority patent/PL1819382T3/en
Priority to EP05796880A priority patent/EP1819382B1/en
Application filed by Novo Nordisk A/S filed Critical Novo Nordisk A/S
Priority to KR1020077011422A priority patent/KR101278123B1/en
Publication of WO2006045528A1 publication Critical patent/WO2006045528A1/en
Priority to IL182616A priority patent/IL182616A0/en
Priority to US13/626,541 priority patent/US8684969B2/en
Priority to US14/167,558 priority patent/US9687611B2/en
Priority to US15/606,147 priority patent/US10471214B2/en
Priority to US16/589,566 priority patent/US11446443B2/en
Priority to US17/885,730 priority patent/US20220379036A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31533—Dosing mechanisms, i.e. setting a dose
    • A61M5/31535—Means improving security or handling thereof, e.g. blocking means, means preventing insufficient dosing, means allowing correction of overset dose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/145—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/145—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons
    • A61M5/1452—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons pressurised by means of pistons
    • A61M5/14566—Pressure infusion, e.g. using pumps using pressurised reservoirs, e.g. pressurised by means of pistons pressurised by means of pistons with a replaceable reservoir for receiving a piston rod of the pump
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31533—Dosing mechanisms, i.e. setting a dose
    • A61M5/31545—Setting modes for dosing
    • A61M5/31548—Mechanically operated dose setting member
    • A61M5/3155—Mechanically operated dose setting member by rotational movement of dose setting member, e.g. during setting or filling of a syringe
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31533—Dosing mechanisms, i.e. setting a dose
    • A61M5/31545—Setting modes for dosing
    • A61M5/31548—Mechanically operated dose setting member
    • A61M5/3155—Mechanically operated dose setting member by rotational movement of dose setting member, e.g. during setting or filling of a syringe
    • A61M5/31553—Mechanically operated dose setting member by rotational movement of dose setting member, e.g. during setting or filling of a syringe without axial movement of dose setting member
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
    • A61M2005/2006—Having specific accessories
    • A61M2005/202—Having specific accessories cocking means, e.g. to bias the main drive spring of an injector
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M2005/3125—Details specific display means, e.g. to indicate dose setting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31533—Dosing mechanisms, i.e. setting a dose
    • A61M5/31545—Setting modes for dosing
    • A61M5/31548—Mechanically operated dose setting member
    • A61M5/31556—Accuracy improving means
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31565—Administration mechanisms, i.e. constructional features, modes of administering a dose
    • A61M5/31576—Constructional features or modes of drive mechanisms for piston rods
    • A61M5/31583—Constructional features or modes of drive mechanisms for piston rods based on rotational translation, i.e. movement of piston rod is caused by relative rotation between the user activated actuator and the piston rod
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
    • A61M5/31565—Administration mechanisms, i.e. constructional features, modes of administering a dose
    • A61M5/3159—Dose expelling manners
    • A61M5/31593—Multi-dose, i.e. individually set dose repeatedly administered from the same medicament reservoir

Definitions

  • the present invention relates to an injection device, such as a wind-up pen, wherein numerals indicating the dose to be ejected from the injection device are displayed over an angle of rotation exceeding one revolution.
  • the numerals indicating the dose to be ejected are arranged along a helical path, or alternatively, numerals indicating the dose to be ejected are displayed on a counting device.
  • the present invention ensures that an increased accuracy in dose setting may be obtained.
  • the dose setting scale arranged on the outer surface of the barrels or wheels contains only up to 42 scale units with an incremental of 2. Thus, the accuracy when setting a dose is limited by this rather rough incremental.
  • WO 02/053214 discloses an automatic injection device having a dose indicator barrel capable of rotating more than one revolution.
  • the injection device according to WO 02/053214 applies a linear spring to move a piston rod in the distal direction of the injection device.
  • an injection device applying a linear spring has a built-in axial displacement due to compressions and extensions of the linear spring along the axial direction of the injection device. This linear movement may easily be utilized to provide axial movements of the dose indicator barrel.
  • linear springs are highly non-linear in terms of force vs. compression.
  • a linear spring exhibits relative high mechanical looses.
  • torsion spring-based injection device providing an improved and more user friendly dose setting procedure. It is an object of the present invention to provide such torsion spring-based injection device having an expanded dose scale with a high resolution.
  • an injection device comprising
  • a torsion spring operatively connected to a dose setting member, the dose setting member being adapted to set a dose to be ejected from the injection device, and
  • a rotatably mounted display member adapted to display the dose to be ejected from the injection device in accordance with a setting of the dose setting member, the rotatably mounted display member being rotatable over an angle correspondi ng to at least one revolution of the display member.
  • the display member may be adapted to be moved between two end positions. These two end positions may define or set an axial operation range of the display mem ber.
  • the axial operation range of the display member may be associated with a substantially linear working range of the torsion spring.
  • the working range of the torsion spring utilized to move the display member between the two end positions may constitute only a fraction of the available working range provided by the torsion spring. Thus, by applying a torsion spring only a small and linear working range of the available working range is utilized.
  • the display member may comprise a dose indicator barrel having nume rals arranged along a helical path on an outer surface thereof.
  • the injection device may further comprise - a housing
  • piston rod having a threaded outer surface with a drive track arranged in a longitudinal direction of the outer surface of the piston rod
  • the dose setting member is rotatably mounted and defines a passage for the piston rod, the dose setting member further having a guiding track arranged on an inner surface thereof,
  • a rotatable drive member being adapted to at least partly engage with at least part of the drive track of the piston rod so as to drive the piston rod
  • the dose ind icator barrel has a part engaging at least part of the guiding track of the dose setting member, the dose setting member and the dose indicator barrel being movable in relation to each other, the dose indicator barrel further having a threaded outer surface cooperating with a threaded inner portion of the housing whereby the dose indicator barrel undergoes a combined translational and rotational movement in relatio n to the housing upon rotation of the dose setting member, and
  • the injection device has a threaded portion cooperating with thie threaded outer surface of the piston rod so that rotation of the piston rod relative to tr* e housing results in a longitudinal movement of the piston rod.
  • the drive track dose not necessarily extend over the full length of the piston rod.
  • the drive track may in some cases only extend over a part of the full length of the piston rod.
  • the drive track arranged in the piston rod may be an indentation or groove in the longitudinal direction of the piston rod. Alternatively, it may also be a planar surface or two opposing planar surfaces.
  • the injection device further comprises
  • a housing - a piston rod having a threaded outer surface with a track arranged in a longitudinal direction of the outer surface of the piston rod,
  • the dose setting member is rotatably mounted and defi nes a passage for the piston rod, the dose setting member further having a guiding track arranged on an inner surface S thereof,
  • rotatable drive member having a threaded portion cooperating with at least part of the threaded outer surface of the piston rod
  • the dose indicator barrel has a part engaging at least part of the guiding track of the dose setting member, the dose setting member and the dose indicator barrel being movable ) in relation to each other, the dose indicator barrel further having a threaded outer surface cooperating with a threaded inner portion of the housing whereby the dose indicator barrel undergoes a combined translational and rotational movement in relation to the housing upon rotation of the dose setting member, and
  • injection device has a portion at least partly engaging the track of piston rod so 5 that rotation of the drive member relative to the housing results in a longitudinal movement of the piston rod.
  • the drive member may be adapted to be connected to the dose setting member via a ratchet.
  • This ratchet allows the dose setting member to be rotated in both directions so that a given dose may be either increased or reduced. Due to the force provided by the torsion ) spring onto the ratchet, the dose setting member will remain in any position - i.e. dose value - to which it has been brought.
  • the dose setting member may be adapted to be separated from the driving member. This separation may be achieved in several ways. In one way the separation may be obtained by a retraction of the dose setting member in the axial direction of the injection device. The 5 retraction of the dose setting member must be over a distance sufficient to detach the dose setting member or the drive member from the teeth of the ratchet. Other separation mechanisms, such as pushing the dose setting member or twisting the dose setting member are also applicable.
  • the torsion spring may be arranged between the housing and the dose setting member in ) such a way that when the dose setting member is rotated around the piston rod, the torsion spring is strained.
  • the torsion spring may be a helical spring wh ich extends coaxially with the piston rod, and which interconnects the housing and the dose setting member in such a way that rotation of the dose setting member, in order to set the dose, strains the torsion spring.
  • the injection device may further comprise a locking member adapted to fixate the piston rod in such a way that no relative rotation of the piston rod and the housing is possible when the 5 locking member is in its locking position. This fixation may be provided by a direct engagement of the locking member into the track of the piston rod, or via the drive member.
  • the injection device may fu rther comprise a release button adapted to release the locking member from its locking position. Preferably, the release button is positioned in the distal half of the length of the injection device.
  • the injection device may further comprise a first stopping member for defini ng an outer position of the dose indicator barrel. This outer position of the dose indicator barrel may correspond to a maximum obtainable dose. Another outer position of the dose indicator barrel, given by a second stopping member, may define a stop for providing further doses.
  • the stopping members may form integral parts of the inner surface of the housing.
  • the display member may comprise a counting device having two or more display wheels having numerals arranged on an outer surface thereof.
  • the counting device may have a first and a second wheel.
  • the first wheel is rotated via an optional gear mechanism, such as a planet gear.
  • This first wheel may contain numerals with an incremental of one. The total
  • the second wheel next to the first wheel also contains numerals with an i ncremental of 1. However, this second wheel "counts" the number of revolutions of the first wheel, or alternatively, it "counts” the tens of the first wheel with an incremental of one.
  • Fig. 1 shows a cross-sectional view of a first embodiment of the injection device according to the present invention
  • Fig. 2 shows a cross-sectional view (rotated 90 degrees compared to Fig. 1) of a first 30 embodiment of the injection device according to the present invention
  • Fig. 3 shows a detailed cross-sectional view of a first embodiment of the present invention
  • Fig. 4 shows a detailed cross-sectional view of a second embodiment of the present invention
  • Fig. 5 shows a detailed cross-sectional view of a third embodiment of the present invention.
  • the present invention relates to an injection device comprising a torsion spring in combination with a rotatable dose indicator mechanism capable of being rotated at least one revolution - i.e. over an angle larger than 360 degrees.
  • the dose indicator mechanism may be implemented as a barrel (see Figs. 1-4) or as interconnected wheels (see Fig. 5), the latter being operated as a counting device.
  • the dose indicator mechanism of the present invention is rotatable over an angle of rotation corresponding to at least one revolution.
  • the dose setting scale may contain at least 50, 60, 70, 80, 90, 100 units with an incremental of one.
  • Figs. 1-3 show a cross-sectional view of the injection device accord ing to a first embodiment of the present invention.
  • the dose of medicament to be ejected from the injection device is set by rotating dose setting member 1.
  • the dose setting member L is attached to the housing 5 of the injection device via torsion spring 12.
  • energy is accumulated in torsion spring 12. This energy may be released by releasing locking member 4 whereby the piston rod 2 will rotate and move in the distal direction of the injection device.
  • the distal movement of the piston rod 2 is caused by a rotational movement of the piston rod 2 itself in that the piston rod 2 has a threaded outer surface.
  • the threads of the piston rod 2 engage and co- operate with a threaded portion 3 of the injection device causing the piston rod 2 to perform the distal and axial movement.
  • the inner surface of housing 5 of the injection device is provided with threads 10. These threads are adapted to engage and co-operate with outer threads S of a dose indicator barrel 9.
  • the dose indicator barrel 9 engages with sliding track 11 of the dose setting member 1 in such a way that the dose indicator barrel 9 is able to slide in said sliding track 11 in an axial direction of the injection device.
  • the dose indicator barrel 9 rotates with the dose setting member 1 causing the dose indicator barrel 9 to be axially displaced relative to the housing 5.
  • a window is provided in the housing 5 of the injection device. Through this window, the user of the injection device may view the actual dose setting level from numerals (not shown) provided on an exterior surface of the dose indicator barrel 9. The numerals are arranged along a helical path.
  • An advantage of having the numerals arranged along a helical-like path is that a higher angular resolution is obtainable when a dose is to be set. Due to this higher angular resolution a dose can be set with a significantly higher accuracy. This greater accuracy is obtained since the helical-like path allows for more numerals to be arranged on the dose indicator barrel 9 compared to numerals arranged at the same height on the surface of the dose indicator barrel 9.
  • the dose indicator barrel 9 When a dose has been ejected from the injection device, the dose indicator barrel 9 is adapted to be rotated back to its initial position and it is thereby ready to be set to a new dose.
  • the piston rod 2 has a threaded outer surface. This threaded outer surface engages and co-operates with a threaded portion 3 of the injection device.
  • the piston rod 2 is driven by the drive member 6 that engages a track in piston rod 2.
  • the axial movement of the piston rod 2 is provided by rotating piston rod 2 in the threaded portion 3 of the injection device.
  • Drive member 6 may be locked by the locking member 4. In its locked position, drive member 6 is prevented from rotating.
  • the user of the injection device may activate a spring-loaded push button 15 whereby drive member 6 causes the piston rod 2 to rotate in threaded part 3 of the housing whereby the piston rod 2 rotates and travels in the distal direction of the injection device.
  • the injection device ejects automatically.
  • the dose indicator barrel returns to zero dose.
  • the dose setting member 1 and the drive member 6 are mechanically connected via a self- tightening ratchet 13.
  • the self-tightening ratchet 13 has saw-toothed teeth with approximately vertical oriented flanks as the self-tightening flanks.
  • the dose setting member 1 is arranged to be axially retractable over a distance corresponding to the height of the teeth of the one-way ratchet 13.
  • the a mount of reduction obviously depends on the angle of rotation (in the opposite rotation direction as when a dose is set) of the dose setting member 1.
  • the self-tightenin g ratchet may be formed as a separate component having first and second engaging parts. Alternatively, one of these parts may form an integral pa rt of the dose setting member 1, or alternatively, an integral part the drive member 6.
  • Fig. 4 shows a second embodiment of the present invention.
  • the drive member 6 has a threaded portion cooperating with the threaded outer surface of the piston rod 2.
  • the main difference compared to the first em bodiment is that the piston rod 2 is no longer rotatable relative to the housing 5.
  • This non-rotatable relationship is ensured in that the housing of the injection device has a key 14 which at least partly engages the track 7 of piston rod 2.
  • Fig. 5 shows a thi rd embodiment of the present invention.
  • the dose indicator barrel of the first and second embodiment has been replaced by a counting device having two wheels 15, 16.
  • the number of wheels may be chosen arbitrary, but for simplicity, a counting device having only two wheels is illustrated in Fig. 5.
  • the counting device is operated as follows: When the dose setting member 1 is rotated, the wheel closest to the dose setting member 15 is rotated via an optional planet gear 17. This wheel contains numerals with an incremental of one.
  • the total scale on this wheel may contain 10 units distributed over a scale from 0 to 9, or alternatively, the total scale may contain for example 20 units distributed over two scales each having a scale from 0 to 9.
  • the second wheel 16 next to the first wheel 15 also contains numerals with an incremental of 1. However, this second wheel "counts” the number of revolutions of the first wheel, or alternatively, it "counts” the tens of the first wheel with an incremental of one. Alternatively, the second wheel "counts" the number of half resolutions of the first wheel in case the first wheel contains a scale having 20 units.

Abstract

The present invention relates to an injection device comprising a torsion spring operatively connected to a dose setting member being adapted to set a dose to be ejected from the injection device. A rotatably mounted display member adapted to display the dose to be ejected in accordance with a setting of the dose setting member is also provided. The rotatably mounted display member is adapted to be rotated over an angle corresponding to at least one revolution of the display member. The display member may be implemented as a dose indicator barrel having numerals arranged along a helical path on an outer surface thereof, or alternatively, as a counting device having two or more display wheels having numerals arranged on an outer surface thereof.

Description

INJECTION DEVICE WITH TORSION SPRING AND ROTATABLE DISPLAY
FIELD OF THE INVENTION
The present invention relates to an injection device, such as a wind-up pen, wherein numerals indicating the dose to be ejected from the injection device are displayed over an angle of rotation exceeding one revolution. In particular, the numerals indicating the dose to be ejected are arranged along a helical path, or alternatively, numerals indicating the dose to be ejected are displayed on a counting device. The present invention ensures that an increased accuracy in dose setting may be obtained.
BACKGROUND OF THE INVENTION
Various types of automatic injection devices have been described in the literature. A majority of these automatic injection devices apply dose indicator barrels, dose indicator wheels or the like which, during dose setting, are only allowed to rotate less than one single revolution. The fact that the dose indicator barrel is only allowed to rotate less than one revolution during dose setting puts a limit to the obtainable angular resolution. This limited angular resolution also limits the accuracy of the dose setting procedure.
In prior art injection devices the dose setting scale arranged on the outer surface of the barrels or wheels contains only up to 42 scale units with an incremental of 2. Thus, the accuracy when setting a dose is limited by this rather rough incremental.
Examples of "one revolution" barrels or wheel may for example be found in US 5,725,508, EP 0 338 806 or US 5,104,380.
WO 02/053214 discloses an automatic injection device having a dose indicator barrel capable of rotating more than one revolution. However, the injection device according to WO 02/053214 applies a linear spring to move a piston rod in the distal direction of the injection device. Evidently, an injection device applying a linear spring has a built-in axial displacement due to compressions and extensions of the linear spring along the axial direction of the injection device. This linear movement may easily be utilized to provide axial movements of the dose indicator barrel. However, it is a disadvantage that linear springs are highly non-linear in terms of force vs. compression. In addition, a linear spring exhibits relative high mechanical looses. Thus, due to the problems relating to the non-linear properties and relatively high looses there is a need for injection devices having linear and more efficient injection assisting systems. The above-mentioned problems may be solved by applying a torsion sp ring instead of the linear spring. An injection device applying a torsion spring is conceptual Iy different from linear spring-based devices in that torsion-based systems do not have a built-in axial movement of the spring assisting the user in injecting a dose of medica ment from the injection device. The advantages of torsion-based injection devices are many, the greatest of these probably being that torsion springs respond in a linear manner over a large working range.
Thus, there is a need for a torsion spring-based injection device providing an improved and more user friendly dose setting procedure. It is an object of the present invention to provide such torsion spring-based injection device having an expanded dose scale with a high resolution.
SUMMARY OF THE INVENTION
The above-mentioned object is complied with by providing, in a first aspect, an injection device comprising
- a torsion spring operatively connected to a dose setting member, the dose setting member being adapted to set a dose to be ejected from the injection device, and
- a rotatably mounted display member adapted to display the dose to be ejected from the injection device in accordance with a setting of the dose setting member, the rotatably mounted display member being rotatable over an angle correspondi ng to at least one revolution of the display member.
The display member may be adapted to be moved between two end positions. These two end positions may define or set an axial operation range of the display mem ber. The axial operation range of the display member may be associated with a substantially linear working range of the torsion spring. The working range of the torsion spring utilized to move the display member between the two end positions may constitute only a fraction of the available working range provided by the torsion spring. Thus, by applying a torsion spring only a small and linear working range of the available working range is utilized.
The display member may comprise a dose indicator barrel having nume rals arranged along a helical path on an outer surface thereof.
According to a first embodiment of the present invention, the injection device may further comprise - a housing,
- a piston rod having a threaded outer surface with a drive track arranged in a longitudinal direction of the outer surface of the piston rod,
wherein the dose setting member is rotatably mounted and defines a passage for the piston rod, the dose setting member further having a guiding track arranged on an inner surface thereof,
- a rotatable drive member being adapted to at least partly engage with at least part of the drive track of the piston rod so as to drive the piston rod,
wherein the dose ind icator barrel has a part engaging at least part of the guiding track of the dose setting member, the dose setting member and the dose indicator barrel being movable in relation to each other, the dose indicator barrel further having a threaded outer surface cooperating with a threaded inner portion of the housing whereby the dose indicator barrel undergoes a combined translational and rotational movement in relatio n to the housing upon rotation of the dose setting member, and
wherein the injection device has a threaded portion cooperating with thie threaded outer surface of the piston rod so that rotation of the piston rod relative to tr* e housing results in a longitudinal movement of the piston rod.
It is to be understood that the drive track dose not necessarily extend over the full length of the piston rod. For example, the drive track may in some cases only extend over a part of the full length of the piston rod. Also, the drive track arranged in the piston rod may be an indentation or groove in the longitudinal direction of the piston rod. Alternatively, it may also be a planar surface or two opposing planar surfaces.
Similarly, it is to be understood that other arrangements in terms of the positioning of the threaded portion of for example the dose indicator barrel may be arranged differently.
According to a second embodiment of the present invention, the injection device further comprises
- a housing, - a piston rod having a threaded outer surface with a track arranged in a longitudinal direction of the outer surface of the piston rod,
wherein the dose setting member is rotatably mounted and defi nes a passage for the piston rod, the dose setting member further having a guiding track arranged on an inner surface S thereof,
- a rotatable drive member having a threaded portion cooperating with at least part of the threaded outer surface of the piston rod,
wherein the dose indicator barrel has a part engaging at least part of the guiding track of the dose setting member, the dose setting member and the dose indicator barrel being movable ) in relation to each other, the dose indicator barrel further having a threaded outer surface cooperating with a threaded inner portion of the housing whereby the dose indicator barrel undergoes a combined translational and rotational movement in relation to the housing upon rotation of the dose setting member, and
wherein the injection device has a portion at least partly engaging the track of piston rod so 5 that rotation of the drive member relative to the housing results in a longitudinal movement of the piston rod.
The drive member may be adapted to be connected to the dose setting member via a ratchet. This ratchet allows the dose setting member to be rotated in both directions so that a given dose may be either increased or reduced. Due to the force provided by the torsion ) spring onto the ratchet, the dose setting member will remain in any position - i.e. dose value - to which it has been brought.
The dose setting member may be adapted to be separated from the driving member. This separation may be achieved in several ways. In one way the separation may be obtained by a retraction of the dose setting member in the axial direction of the injection device. The 5 retraction of the dose setting member must be over a distance sufficient to detach the dose setting member or the drive member from the teeth of the ratchet. Other separation mechanisms, such as pushing the dose setting member or twisting the dose setting member are also applicable.
The torsion spring may be arranged between the housing and the dose setting member in ) such a way that when the dose setting member is rotated around the piston rod, the torsion spring is strained. The torsion spring may be a helical spring wh ich extends coaxially with the piston rod, and which interconnects the housing and the dose setting member in such a way that rotation of the dose setting member, in order to set the dose, strains the torsion spring.
The injection device may further comprise a locking member adapted to fixate the piston rod in such a way that no relative rotation of the piston rod and the housing is possible when the 5 locking member is in its locking position. This fixation may be provided by a direct engagement of the locking member into the track of the piston rod, or via the drive member. The injection device may fu rther comprise a release button adapted to release the locking member from its locking position. Preferably, the release button is positioned in the distal half of the length of the injection device.
LO The injection device may further comprise a first stopping member for defini ng an outer position of the dose indicator barrel. This outer position of the dose indicator barrel may correspond to a maximum obtainable dose. Another outer position of the dose indicator barrel, given by a second stopping member, may define a stop for providing further doses. The stopping members may form integral parts of the inner surface of the housing.
L5 In a third embodiment, the display member may comprise a counting device having two or more display wheels having numerals arranged on an outer surface thereof. In this second embodiment the counting device may have a first and a second wheel. When the dose setting member is rotated, the first wheel is rotated via an optional gear mechanism, such as a planet gear. This first wheel may contain numerals with an incremental of one. The total
>0 scale on this wheel may be from 0 to 9. The second wheel next to the first wheel also contains numerals with an i ncremental of 1. However, this second wheel "counts" the number of revolutions of the first wheel, or alternatively, it "counts" the tens of the first wheel with an incremental of one.
BRIEF DESCRIPTION OF TH E DRAWINGS
>5 The present invention will now be described in further details with reference to the accompanying figures, wherein
Fig. 1 shows a cross-sectional view of a first embodiment of the injection device according to the present invention,
Fig. 2 shows a cross-sectional view (rotated 90 degrees compared to Fig. 1) of a first 30 embodiment of the injection device according to the present invention,
Fig. 3 shows a detailed cross-sectional view of a first embodiment of the present invention, Fig. 4 shows a detailed cross-sectional view of a second embodiment of the present invention, and
Fig. 5 shows a detailed cross-sectional view of a third embodiment of the present invention.
While the invention is susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and will be described in detail herein. It should be understood, however, that the invention is not intended to be limited to the particular forms disclosed. Rather, the invention is to cover all modifications, equiva lents, and alternatives falling within the spirit and scope of tine invention as defined by the appended claims.
DETAILED DESCRIPTION OF THE INVENTION
In its most general aspect the present invention relates to an injection device comprising a torsion spring in combination with a rotatable dose indicator mechanism capable of being rotated at least one revolution - i.e. over an angle larger than 360 degrees. For example, the dose indicator mechanism may be implemented as a barrel (see Figs. 1-4) or as interconnected wheels (see Fig. 5), the latter being operated as a counting device. In order to increase the angular resolution compared to known dose indicator mechanisms the dose indicator mechanism of the present invention is rotatable over an angle of rotation corresponding to at least one revolution. The fact that the dose to be ejected is displayed over at least one revolution allows that the dose setting scale may contain at least 50, 60, 70, 80, 90, 100 units with an incremental of one.
Figs. 1-3 show a cross-sectional view of the injection device accord ing to a first embodiment of the present invention. The dose of medicament to be ejected from the injection device is set by rotating dose setting member 1. The dose setting member L is attached to the housing 5 of the injection device via torsion spring 12. When the dose setting member 1 is rotated in order to set a dose to be ejected from the injection device, energy is accumulated in torsion spring 12. This energy may be released by releasing locking member 4 whereby the piston rod 2 will rotate and move in the distal direction of the injection device. The distal movement of the piston rod 2 is caused by a rotational movement of the piston rod 2 itself in that the piston rod 2 has a threaded outer surface. The threads of the piston rod 2 engage and co- operate with a threaded portion 3 of the injection device causing the piston rod 2 to perform the distal and axial movement.
The inner surface of housing 5 of the injection device is provided with threads 10. These threads are adapted to engage and co-operate with outer threads S of a dose indicator barrel 9. The dose indicator barrel 9 engages with sliding track 11 of the dose setting member 1 in such a way that the dose indicator barrel 9 is able to slide in said sliding track 11 in an axial direction of the injection device.
When the dose setting member 1 is rotated in order to set a dose, the dose indicator barrel 9 rotates with the dose setting member 1 causing the dose indicator barrel 9 to be axially displaced relative to the housing 5. A window is provided in the housing 5 of the injection device. Through this window, the user of the injection device may view the actual dose setting level from numerals (not shown) provided on an exterior surface of the dose indicator barrel 9. The numerals are arranged along a helical path.
An advantage of having the numerals arranged along a helical-like path is that a higher angular resolution is obtainable when a dose is to be set. Due to this higher angular resolution a dose can be set with a significantly higher accuracy. This greater accuracy is obtained since the helical-like path allows for more numerals to be arranged on the dose indicator barrel 9 compared to numerals arranged at the same height on the surface of the dose indicator barrel 9.
When a dose has been ejected from the injection device, the dose indicator barrel 9 is adapted to be rotated back to its initial position and it is thereby ready to be set to a new dose. The same applies for an injection device applying a counting device as a dose meter.
As already mentioned, the piston rod 2 has a threaded outer surface. This threaded outer surface engages and co-operates with a threaded portion 3 of the injection device. The piston rod 2 is driven by the drive member 6 that engages a track in piston rod 2. The axial movement of the piston rod 2 is provided by rotating piston rod 2 in the threaded portion 3 of the injection device. Drive member 6 may be locked by the locking member 4. In its locked position, drive member 6 is prevented from rotating. In order to release the drive member 6, the user of the injection device may activate a spring-loaded push button 15 whereby drive member 6 causes the piston rod 2 to rotate in threaded part 3 of the housing whereby the piston rod 2 rotates and travels in the distal direction of the injection device. Thus, when the drive member 6 is released, the injection device ejects automatically. During ejection, the dose indicator barrel returns to zero dose.
The dose setting member 1 and the drive member 6 are mechanically connected via a self- tightening ratchet 13. Preferably, the self-tightening ratchet 13 has saw-toothed teeth with approximately vertical oriented flanks as the self-tightening flanks. In order to reset or reduce an already set dose, the dose setting member 1 is arranged to be axially retractable over a distance corresponding to the height of the teeth of the one-way ratchet 13. Thus, by pulling the dose setting member 1 back, and thereby disengage the dose setting member 1 from the drive member 6, an already set dose can be reduced or even reset. The a mount of reduction obviously depends on the angle of rotation (in the opposite rotation direction as when a dose is set) of the dose setting member 1.
The self-tightenin g ratchet may be formed as a separate component having first and second engaging parts. Alternatively, one of these parts may form an integral pa rt of the dose setting member 1, or alternatively, an integral part the drive member 6.
Fig. 4 shows a second embodiment of the present invention. Compared to the first embodiment, the drive member 6 has a threaded portion cooperating with the threaded outer surface of the piston rod 2. The main difference compared to the first em bodiment is that the piston rod 2 is no longer rotatable relative to the housing 5. This non-rotatable relationship is ensured in that the housing of the injection device has a key 14 which at least partly engages the track 7 of piston rod 2. Thus, when the drive member 6 is free to rotate relative to the housing 5 the piston rod 2 will undergo a translational movement along the axial direction of the injection device.
Fig. 5 shows a thi rd embodiment of the present invention. In this embodi ment the dose indicator barrel of the first and second embodiment has been replaced by a counting device having two wheels 15, 16. In principle the number of wheels may be chosen arbitrary, but for simplicity, a counting device having only two wheels is illustrated in Fig. 5. The counting device is operated as follows: When the dose setting member 1 is rotated, the wheel closest to the dose setting member 15 is rotated via an optional planet gear 17. This wheel contains numerals with an incremental of one. The total scale on this wheel may contain 10 units distributed over a scale from 0 to 9, or alternatively, the total scale may contain for example 20 units distributed over two scales each having a scale from 0 to 9.
The second wheel 16 next to the first wheel 15 also contains numerals with an incremental of 1. However, this second wheel "counts" the number of revolutions of the first wheel, or alternatively, it "counts" the tens of the first wheel with an incremental of one. Alternatively, the second wheel "counts" the number of half resolutions of the first wheel in case the first wheel contains a scale having 20 units.

Claims

1. An injection device comprising
- a torsion spring (12) operatively connected to a dose setting member (1), the dose setting member (1) being adapted to set a dose to be ej ected from the injection device,
> and
- a rotatably mounted display member adapted to displa y the dose to be ejected from the injection device in accordance with a setting of the dose setting member (1), the rotatably mounted display member being rotatabie over an angle corresponding to at least one revolution of the display member.
) 2. An injection device according to claim 1, wherein the disp> lay member is adapted to be moved between two end positions, said two end positions defining an operation range of the display member, said operation range being associated with a substantially linear working range of the torsion spring.
3. An injection device according to claim 1 or 2, wherein the display member comprises a
> dose indicator barrel (9) having numerals arranged along a .helical path on an outer surface thereof.
4. An injection device according to claim 1, wherein the disp lay member comprises a counting device having two or more display wheels having n umerals arranged on an outer surface thereof.
)
5. An injection device according to claim 2 or 3, further com prising
- a housing (5),
- a piston rod (2) having a threaded outer surface with a drive track (7) arranged in a longitudinal direction of said outer surface,
wherein the dose setting member (1) is rotatably mounted and defines a passage for the
> piston rod (2), the dose setting member (1) further having a guiding track (11) arranged on an inner surface thereof, - a rotatable drive member (6) being adapted to at least partly engage with at least part of the drive track (7) of the piston rod (2) so as to drive the piston rod,
wherein the dose indicator barrel (9) has a part engaging at least part of the guiding track (11) of the dose setting member (1), the dose setting member (1) and the dose indicator 5 barrel (9) being movable in relation to each other, trie dose indicator barrel (9) further having a threaded outer surface (8) cooperating withi a threaded inner portion (10) of the housing (5) whereby the dose indicator barrel (9) undergoes a combined translational and rotational movement in relation to the housing (5) upon rotation of the dose setting member (1), and
O wherein the injection device has a threaded portion C 3) cooperating with the threaded outer surface of the piston rod (2) so that rotation of the piston rod (2) relative to the housing (5) results in a longitudinal movement of the piston rod (2).
6. An injection device according to claim 2 or 3, further comprising
- a housing (5),
.5 - a piston rod (2) having a threaded outer surface with a track (7) arranged in a longitudinal direction of said outer surface,
wherein the dose setting member (1) is rotatably mounted and defines a passage for the piston rod (2), the dose setting member (1) further having a guiding track (11) arranged on an inner surface thereof,
!0 - a rotatable drive member (6) having a threaded portion cooperating with at least part of the threaded outer surface of the piston rod (2),
wherein the dose indicator barrel (9) has a part enga ging at least part of the guiding track (11) of the dose setting member (1), the dose setting member (1) and the dose indicator barrel (9) being movable in relation to each other, the dose indicator barrel (9) further [5 having a threaded outer surface (8) cooperating with a threaded inner portion (10) of the housing (5) whereby the dose indicator barrel (9) undergoes a combined translational and rotational movement in relation to the housing (5) upon rotation of the dose setting member (1), and wherein the injection device has a portion at least partly engaging the track (7) of piston rod (2) so that rotation of the drive member (6) relative to the housing (5) results in a longitudinal movement of the piston rod (2).
7. An injection device according to claim 5 or 6, wherein the drive member (6) is adapted to be connected to the dose setting member (1) via a ratchet (13).
8. An injection device according to any of claims 5-7, wherein the torsion spring (12) is arranged between the housing (5) and the dose setting member (1) in such a way that when the dose setting member (1) is rotated around the piston rod (2), the torsion spring (12) is strained.
9. An injection device according to claim 8, wherein the torsion spring (12) is a helical spring which extends coaxially with the piston rod (2).
10. An injection device according to any of claims 5-9, further comprising a locking member (4) adapted to fixate the piston rod (2) in such a way that no relative rotation between of the piston rod (2) and the housing (5) is possible when the locking member (4) is in its locking
5 position.
11. An injection device according to claim 10, further comprising a release button adapted to release the locking member (4) from its locking position.
12. An injection device according to claim 11, wherein the release button is positioned in the distal half of the length of the injection device.
D 13. An injection device according to any of claims 5-12, further comprising a stopping member for defining an outer position of the dose indicator barrel (9), the outer position of the dose indicator barrel (9) correspond ing to a maximum obtainable dose.
PCT/EP2005/011287 2004-10-21 2005-10-20 Injection device with torsion spring and rotatable display WO2006045528A1 (en)

Priority Applications (17)

Application Number Priority Date Filing Date Title
JP2007537215A JP5185620B2 (en) 2004-10-21 2005-10-20 Injection device with torsion spring and rotary indicator
EP05796880A EP1819382B1 (en) 2004-10-21 2005-10-20 Injection device with torsion spring and rotatable display
PL05796880T PL1819382T3 (en) 2004-10-21 2005-10-20 Injection device with torsion spring and rotatable display
DK05796880.2T DK1819382T3 (en) 2004-10-21 2005-10-20 Injection device with torsion spring and swivel display
AU2005298946A AU2005298946B2 (en) 2004-10-21 2005-10-20 Injection device with torsion spring and rotatable display
AT05796880T ATE445430T1 (en) 2004-10-21 2005-10-20 INJECTION DEVICE WITH TORSION SPRING AND ROTATABLE DISPLAY
US11/665,571 US8357120B2 (en) 2004-10-21 2005-10-20 Injection device with torsion spring and rotatable display
CA2584762A CA2584762C (en) 2004-10-21 2005-10-20 Injection device with torsion spring and rotatable display
CN2005800396135A CN101084028B (en) 2004-10-21 2005-10-20 Injection device with torsion spring and rotatable display
DE602005017182T DE602005017182D1 (en) 2004-10-21 2005-10-20 INJECTION DEVICE WITH TORSION SPRING AND ROTATABLE DISPLAY
KR1020077011422A KR101278123B1 (en) 2004-10-21 2005-10-20 Injection device with torsion spring and rotatable display
IL182616A IL182616A0 (en) 2004-10-21 2007-04-17 Injection device with torsion spring and rotatable display
US13/626,541 US8684969B2 (en) 2004-10-21 2012-09-25 Injection device with torsion spring and rotatable display
US14/167,558 US9687611B2 (en) 2004-10-21 2014-01-29 Injection device with torsion spring and rotatable display
US15/606,147 US10471214B2 (en) 2004-10-21 2017-05-26 Injection device with torsion spring and rotatable display
US16/589,566 US11446443B2 (en) 2004-10-21 2019-10-01 Injection device with torsion spring and rotatable display
US17/885,730 US20220379036A1 (en) 2004-10-21 2022-08-11 Injection device with torsion spring and rotatable display

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP04077899 2004-10-21
EP04077899.5 2004-10-21

Related Child Applications (2)

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US11/665,571 A-371-Of-International US8357120B2 (en) 2004-10-21 2005-10-20 Injection device with torsion spring and rotatable display
US13/626,541 Continuation US8684969B2 (en) 2004-10-21 2012-09-25 Injection device with torsion spring and rotatable display

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US (6) US8357120B2 (en)
EP (1) EP1819382B1 (en)
JP (1) JP5185620B2 (en)
KR (1) KR101278123B1 (en)
CN (1) CN101084028B (en)
AT (1) ATE445430T1 (en)
AU (1) AU2005298946B2 (en)
CA (1) CA2584762C (en)
DE (1) DE602005017182D1 (en)
DK (1) DK1819382T3 (en)
ES (1) ES2334808T3 (en)
IL (1) IL182616A0 (en)
PL (1) PL1819382T3 (en)
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ATE445430T1 (en) 2009-10-15
DE602005017182D1 (en) 2009-11-26
US20200030541A1 (en) 2020-01-30
US8684969B2 (en) 2014-04-01
US20220379036A1 (en) 2022-12-01
US20130035641A1 (en) 2013-02-07
KR20070084392A (en) 2007-08-24
JP5185620B2 (en) 2013-04-17
DK1819382T3 (en) 2010-02-15
US8357120B2 (en) 2013-01-22
AU2005298946B2 (en) 2011-06-09
JP2008517233A (en) 2008-05-22
KR101278123B1 (en) 2013-06-24
CA2584762C (en) 2014-03-18
EP1819382A1 (en) 2007-08-22
RU2007114760A (en) 2008-11-27
US20090054839A1 (en) 2009-02-26
US20170259005A1 (en) 2017-09-14
AU2005298946A1 (en) 2006-05-04
ES2334808T3 (en) 2010-03-16
CN101084028A (en) 2007-12-05
US11446443B2 (en) 2022-09-20
US20140303563A1 (en) 2014-10-09
EP1819382B1 (en) 2009-10-14
PL1819382T3 (en) 2010-03-31
RU2388498C2 (en) 2010-05-10
US9687611B2 (en) 2017-06-27
CA2584762A1 (en) 2006-05-04
US10471214B2 (en) 2019-11-12
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ZA200703706B (en) 2008-09-25
IL182616A0 (en) 2007-07-24

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