Injection device with distraction mechanism

Abstract

The present disclosure relates to features of an injection device that are arranged to provide a sensory distraction to a user during insertion of a needle into the skin. According to a first aspect, the present disclosure discloses an injection device including: an elongated housing having a proximal end and a distal end and configured to receive a container of a medicament; a needle housing for holding a needle at a position at the distal end of the elongated housing; and a needle sleeve mounted within the housing, wherein the needle sleeve and the needle housing are movable relative to each other by user manipulation between a first configuration in which the needle sleeve surrounds a needle held in a needle holder and a second configuration in which the needle held in the needle housing extends distally from the needle sleeve, and wherein the needle sleeve includes a portion configured to vibrate and / or rotate using energy from the user manipulation during movement between the first and second configurations.

Description

[Technical field]

[0001] The present disclosure relates to features of an injection device that are arranged to provide a sensory distraction to the user during insertion of the needle into the skin. [Background technology]

[0002] Injection devices, such as auto-injectors, are known in the art for administering medication to an injection site of a patient. Such injection devices often include a body portion and a cap, where a needle syringe is located within the body portion and the cap is removably attached to the body portion to shield the needle of the needle syringe. To administer the medication, the cap is first removed from the body portion to expose the needle. The needle is then inserted into the patient's body at the injection site to administer the medication.

[0003] The insertion of a needle into a user's body is often associated with pain and discomfort to the user. In addition, the user may become anxious and tense during needle insertion, resulting in further pain. Summary of the Invention [Means for solving the problem]

[0004] According to a first aspect, the present specification discloses an injection device including: an elongate housing having a proximal end and a distal end and configured to receive a container of a medicament; a needle housing for holding a needle at a position at the distal end of the elongate housing; and a needle sleeve mounted within the housing, wherein the needle sleeve and the needle housing are movable relative to one another by user manipulation between a first configuration in which the needle sleeve surrounds a needle held in a needle holder and a second configuration in which the needle held in the needle housing extends distally from the needle sleeve, and wherein the needle sleeve includes a portion configured to vibrate and / or rotate using energy from the user manipulation during movement between the first and second configurations.

[0005] In a first configuration, the needle sleeve can be in an extended position in which the needle sleeve extends at least partially from the distal end of the housing. In a second configuration, the needle sleeve can be in a retracted position in which the needle sleeve is received deeper within the housing than in the extended position. The needle housing is substantially fixed relative to the elongate housing such that when the needle sleeve is in the extended position, the needle is concealed and when the needle sleeve is in the retracted position, the needle is exposed.

[0006] The needle sleeve may include an outer sleeve and an inner sleeve, the inner sleeve including a portion configured to oscillate and / or rotate. The outer sleeve may extend distally beyond the inner sleeve.

[0007] The inner sleeve may include one or more recessed tracks. The housing may include one or more engagement portions arranged to couple with the one or more tracks to cause oscillation and / or rotation of the inner sleeve during movement of the needle sleeve between the extended and retracted positions. The one or more tracks extend helically around the inner sleeve, where the inner sleeve is free to rotate relative to the elongated housing. The one or more tracks are in a zigzag form on a surface of the inner sleeve, thereby causing the inner sleeve to oscillate during movement between the first and second configurations. The one or more engagement portions may include a ratchet device configured to resist movement between the first and second configurations and not resist movement between the second and first configurations.

[0008] The user operation may include manually depressing the elongate housing laterally in a distal direction.

[0009] The portion of the needle sleeve configured to vibrate and / or rotate may include one or more distally extending brushes. The portion of the needle sleeve configured to vibrate and / or rotate may alternatively or additionally include one or more distally extending protrusions and / or peaks. The portion of the needle sleeve configured to vibrate and / or rotate may alternatively or additionally include one or more piezoelectric devices.

[0010] The injection device further includes: a piston rod longitudinally movable within the housing; and a piston spring configured to bias the piston rod toward a distal end of the housing to engage a container of medicament when received within the housing, wherein the needle sleeve is configured to inhibit vibration and / or rotation of the portion during longitudinal movement of the piston rod in the distal direction.

[0011] The injection device further includes: a piston rod longitudinally movable within the housing; and a piston spring configured to bias the piston rod toward a distal end of the housing to engage a container of medicament when received within the housing, wherein the portion of the needle sleeve configured to oscillate and / or rotate is further configured to oscillate and / or rotate during longitudinal movement of the piston rod in the distal direction.

[0012] The needle sleeve is fixed relative to the elongate housing, in a first configuration the needle housing is in a retracted position in which a needle retained within the needle housing is obscured by the needle sleeve, and in a second configuration the needle housing is in an extended position in which a needle within the needle housing extends distally beyond the needle sleeve.

[0013] The injection device further includes a needle for expelling medicament from the injection device, the needle being held at a position at the distal end of the elongate housing that is substantially fixed relative to the elongate housing such that the needle is concealed when the needle sleeve is in the extended position and the needle is exposed when the needle sleeve is in the retracted position.

[0014] The injection device may further include a container of medication received within the housing.

[0015] According to a further aspect, the present specification discloses a method of using an injection device, the method including: preparing the injection device in a first configuration; and applying a user action to change a configuration of the user device from the first configuration to a second configuration.

[0016] According to further aspects, the present specification discloses a method for causing vibration and / or rotation of a portion of an injection device, the injection device having a distal end and a proximal end, the distal end including a needle sleeve and a needle, the method including: moving the injection device under user manipulation between a first configuration in which the needle sleeve surrounds the needle and a second configuration in which the needle extends distally beyond the needle sleeve; and using energy from the user manipulation to vibrate and / or rotate a portion of the distal end of the injection device during movement between the first and second configurations.

[0017] Embodiments will now be described, by way of non-limiting examples, with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0018] [Figure 1a] FIG. 1 illustrates an exemplary drug delivery device. [Figure 1b] FIG. 1 illustrates an exemplary drug delivery device. [Diagram 2] FIG. 1 shows an example of a distal end of an injection device. [Diagram 3] 1A-1D are cross-sectional views of an embodiment of an injection device. [Figure 4a] FIG. 13 shows an example of a surface pattern at the distal end of the distraction portion of an injection device. [Figure 4b] FIG. 13 shows an example of a surface pattern at the distal end of the distraction portion of an injection device. [Figure 4c]FIG. 13 shows an example of a surface pattern at the distal end of the distraction portion of an injection device. [Diagram 5] FIG. 1 is a cutaway view of an embodiment of an injection device. [Figure 6a] 13A-13C show examples of trajectories for use on the inner sleeve of the needle housing. [Figure 6b] 13A-13C show examples of trajectories for use on the inner sleeve of the needle housing. [Figure 6c] 13A-13C show examples of trajectories for use on the inner sleeve of the needle housing. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] Drug delivery devices as described herein are configured to inject medication into a patient. For example, delivery is subcutaneous, intramuscular, or intravenous. Such devices are operated by the patient or a caregiver such as a nurse or physician and can include various types of safety syringes, pen injectors, or auto-injectors. The devices can include cartridge-based systems that require a sealed ampoule to be pierced prior to use. The amount of medication delivered with these various devices can range from about 0.5 ml to about 3 ml. Another device can include a large volume device ("LVD") or patch pump that is configured to adhere to the patient's skin for a period of time (e.g., about 5, 15, 30, 60, or 120 minutes) to deliver a "large" volume of medication (typically about 2 ml to about 50 ml). Yet another device can include a pre-filled syringe within the housing of the device. The syringe is fixed within the housing or is movable within the housing, for example, from a retracted position to an operational extended position.

[0020] In combination with a particular drug, the devices described herein are also customized to operate within the required specifications. For example, the device is customized to inject the drug within a particular time period (e.g., about 3 seconds to about 20 seconds for an autoinjector, about 10 minutes to about 60 minutes for an LVD). Other specifications can include low or minimal levels of discomfort, or specific conditions regarding human factors, shelf life, expiration date, biocompatibility, environmental considerations, etc. Such variations can arise due to a variety of factors, such as, for example, drugs ranging in viscosity from about 3 cP to about 50 cP. As a result, drug delivery devices often include hollow needles ranging in size from about 25 to about 31 gauge. Common sizes are 17 and 29 gauge.

[0021] The delivery devices described herein may also include one or more automated features. For example, one or more of needle and cartridge coupling, needle insertion, drug injection, and needle retraction may be automated. Energy for one or more automated steps is provided by one or more energy sources. The energy sources may include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, a mechanical energy source may include a spring, lever, elastomer, or other mechanical mechanism to store or release energy. One or more energy sources may be combined into a single device. The device may further include gears, valves, or other mechanisms to convert energy into movement of one or more components of the device.

[0022] The one or more automatic functions of the auto-injector are each activated by an activation mechanism. Such an activation mechanism may include one or more of an actuator, e.g., a button, a lever, a needle sleeve, or other activation components. Activation of the automatic function may be a one-step or a multi-step process. That is, a user may be required to activate one or more activation components to trigger the automatic function. For example, in a one-step process, a user may depress a needle sleeve against the user's body to trigger an injection of the medication. Other devices may require multi-step activation of the automatic function. For example, a user may be required to depress a button and retract a needle shield to trigger an injection.

[0023] Additionally, activation of one automated function may activate one or more subsequent automated functions, thereby forming an activation sequence. For example, activation of a first automated function may activate at least two of needle and cartridge coupling, needle insertion, drug injection, and needle retraction. Some devices may also require a specific sequence of steps to cause one or more automated functions to occur. Other devices may operate with independent sequence of steps.

[0024] Some delivery devices can include one or more features of a safety syringe, a pen injector, or an auto-injector. For example, a delivery device can include a mechanical energy source (as typically found in an auto-injector) configured to automatically inject a medication, and a dose setting mechanism (as typically found in a pen injector).

[0025] According to some embodiments of the present disclosure, an exemplary drug delivery device 10 is shown in Figures 1A and 1B. The device 10, as described above, is configured to inject a medication into a patient's body. The device 10 includes a housing 11 that typically includes a cartridge or pre-filled syringe that defines a reservoir containing the medication to be injected, and components required to facilitate one or more steps of the delivery process.

[0026] The device 10 may also include a cap 12 that is removably attached to the housing 11. Typically, a user must remove the cap 12 from the housing 11 before the device 10 can be operated.

[0027] As shown, the housing 11 is substantially cylindrical and has a substantially constant diameter along a longitudinal axis AA. The housing 11 has a distal region D and a proximal region P. The term "distal" refers to a location relatively closer to the site of injection and the term "proximal" refers to a location relatively further from the site of injection.

[0028] The device 10 can also include a needle sleeve 19 coupled to the housing 11 to permit movement of the sleeve 19 relative to the housing 11. For example, the sleeve 19 can move in a longitudinal direction parallel to the longitudinal axis AA. Specifically, movement of the sleeve 19 in the proximal direction can permit the needle 17 to extend from a distal region D of the housing 11. In some embodiments, the needle sleeve 19 is alternatively fixed relative to the housing 11 or formed as part of the housing 11.

[0029] Insertion of needle 17 can occur via several mechanisms. For example, needle 17 may be fixedly positioned relative to housing 11, e.g., within a needle housing (not shown), and initially positioned within an extended needle sleeve 19. Proximal movement of sleeve 19 by placing the distal end of sleeve 19 against the patient's body and moving housing 11 distally will uncover the distal end of needle 17. Such relative movement allows the distal end of needle 17 to extend into the patient's body. Such insertion is referred to as a "manual" insertion, since needle 17 is manually inserted by the patient's manual movement of housing 11 relative to sleeve 19.

[0030] Another form of insertion is "automated," whereby needle 17 moves relative to housing 11. Such insertion is triggered by movement of sleeve 19 or by another form of actuation, such as, for example, button 13. As shown in Figures 1A and 1B, button 13 is located at the proximal end of housing 11. However, in other embodiments, button 13 is located on the side of housing 11.

[0031] Other manual or automated functions can include drug injection or needle insertion, or both. Injection is the process in which the bung or piston 14 is moved from a proximal location to a more distal location within the reservoir of the cartridge 18 to force the medicament out of the cartridge 18 through the needle 17. In some embodiments, the drive spring (not shown) is under compression before the device 10 is activated. The proximal end of the drive spring is fixed within the proximal region P of the housing 11, and the distal end of the drive spring is configured to apply a compressive force to the proximal surface of the piston 14 (also referred to as the "plunger"). After activation, at least a portion of the energy stored in the drive spring is applied to the proximal surface of the piston 14. This compressive force acts against the piston 14 to move it in a distal direction. Such distal movement acts to compress the liquid medicament within the cartridge 18 and force it out of the needle 17. Such distal movement is referred to as "pushing down" the piston 14.

[0032] After injection, needle 17 is retracted within sleeve 19 or housing 11. Retraction may occur when sleeve 19 moves distally as the user removes device 10 from the patient's body. This may occur because needle 17 remains fixedly positioned relative to housing 11. Once the distal end of sleeve 19 passes the distal end of needle 17 and needle 17 is sheathed, sleeve 19 is locked. Such locking may include locking any proximal movement of sleeve 19 relative to housing 11.

[0033] Another form of needle retraction may occur when the needle 17 is moved relative to the housing 11. Such movement may occur when the cartridge 18 within the housing 11 is moved proximally relative to the housing 11. This proximal movement is accomplished using a retraction spring (not shown) located in the distal region D. When activated, the compressed retraction spring can provide sufficient force to the cartridge 18 to move it proximally. After sufficient retraction, the relative movement between the needle 17 and the housing 11 is locked by a locking mechanism. Additionally, the button 13 or other components of the device 10 may be locked as desired.

[0034] In some embodiments, the injection device is a needle-free device, such as a jet injector. In this type of device, there is no needle. The agent is administered by expelling the agent from the injection device as a high pressure stream of liquid that penetrates the recipient's skin.

[0035] FIG. 2 shows a diagram of an example of a distal end of an injection device. The distal end 20 of the injection device includes a needle sleeve 19 that includes a portion 21 (also referred to herein as a "distraction portion") configured to oscillate and / or rotate during movement of the needle sleeve 19 between an extended position and a retracted position. The needle sleeve 19 is positioned to obscure (i.e., cover) the needle 17 when in the extended position and to expose the needle 17 when in the retracted position. The configuration in which the needle sleeve 19 obscures the needle is referred to herein as the "first configuration" and the configuration in which the needle is exposed is referred to as the "second configuration." In FIG. 2, the needle sleeve 19 is in the extended position (i.e., the first configuration).

[0036] User actuation / manipulation moves needle sleeve 19 between an extended position and a retracted position. Needle sleeve 19 is configured to use energy from user actuation / manipulation to cause vibration and / or rotation of distraction portion 21, thereby providing sensory distraction from the penetration of needle 17 into the skin.

[0037] For example, when performing an injection, a user may place the distal end of needle sleeve 19, when in the extended position, at a target injection site on the skin. The user applies a force to housing 11 in a distal direction by grasping housing 11 and pushing it toward the injection site, causing housing 11 to move laterally toward the injection site. This action is referred to herein as "pushing down" the housing. Needle sleeve 19 retracts into housing 11 as housing 11 moves laterally. Because needle 17 is fixed relative to the housing, needle 17 extends from needle sleeve 19 and pierces the skin at the injection site during this movement of the housing.

[0038] During retraction of the needle sleeve 19 into the housing, the distraction portion 21 provides sensory stimulation to the area of ​​the injection site by vibrating and / or rotating. The energy required to provide such vibration / rotation is extracted from the depression of the housing 11. For example, a peak within the needle sleeve 19 / distraction portion 21 may rub / vibrate against the inner surface of the housing 11 to create a vibration sensation during depression to distract from the pain of needle 17 insertion. Other examples of how the vibration / rotation of the distraction portion 21 is provided are described below.

[0039] 2, the distraction portion 21 is provided by one or more rings at the distal end of the needle sleeve 19 that are configured to rotate and / or oscillate during depression of the housing 11. The one or more rings / distraction portions 21 may be positioned such that they are not under pressure during depression of the housing 11, i.e., such that they do not directly contact the skin at the injection site, even under high pressure.

[0040] In addition to vibrating / rotating during retraction of the needle housing 19, the distraction portion 21 may also vibrate and / or rotate in some embodiments during the injection itself, i.e., during depression of the plunger / bung / piston into the drug cartridge. The plunger / piston may engage with the needle sleeve 19 to cause the needle sleeve 19 to vibrate / rotate using energy from the plunger depression. The needle sleeve 19 may include internal features that engage with the plunger / piston to cause the vibration / rotation. For example, the inside of the needle sleeve 19 is contoured and in contact with the piston / plunger, so that the movement of the piston / plunger causes the needle sleeve 19 to vibrate. Alternatively, the needle sleeve may have internal tracks that engage with features on the piston / plunger in a manner similar to the features on the housing 11. This may provide distraction to the user throughout the entire process of the injection, i.e., from needle insertion to the end of drug delivery.

[0041] In another embodiment, the needle sleeve 19 is configured not to rotate / vibrate during depression of the piston into the drug cartridge, which prevents the needle 17 from being moved during release of the drug, which may cause additional pain.

[0042] In some embodiments, the needle sleeve 19 is fixed relative to the housing 11 with the needle housing movable relative to the housing 11 between a position in which the needle 17 held within the needle housing is obscured by the needle sleeve 19 (i.e., a first configuration) and a position in which the needle 17 held within the needle housing extends distally beyond the needle sleeve 19 (i.e., a second configuration). The portion of the needle sleeve 19 that is configured to oscillate and / or rotate uses energy from a user manipulation during movement between the first and second configurations.

[0043] Generally, relative motion between the needle sleeve 19 and the needle housing is used to move between a first configuration in which the needle 17 held by the needle housing is obscured by the needle sleeve, and a second configuration in which the needle 17 held by the needle housing extends distally beyond the needle sleeve 19. Energy from this relative motion is used to vibrate and / or rotate a portion of the needle sleeve 19 to provide distraction. One of the needle sleeve 19 and the needle housing is fixed relative to the housing 11. Alternatively, both the needle sleeve 19 and the needle housing are movable relative to the housing 11.

[0044] In needle-free injection devices, the vibrating and / or rotating portion may be present at the distal end of the housing (i.e., the portion of the injection device that contacts the patient's skin during needle-free injection) to provide distraction during skin penetration by the high pressure drug stream. The mechanism used to generate the high pressure stream of drug is also used to provide energy for the vibration and / or rotation of the vibrating and / or rotating portion. Alternatively, the vibrating and / or rotating portion is powered separately.

[0045] 3 shows a cross-sectional view of an embodiment of an injection device 30. In some embodiments, such as the one shown here, the needle sleeve 19 includes an inner sleeve 22 and an outer sleeve 23. The inner sleeve 22 includes a distraction portion 21 - i.e., a portion configured to vibrate and / or rotate during depression of the housing 11. The outer sleeve 23 may extend further distally than the inner sleeve 22 such that the outer sleeve 23 contacts the user's skin during use and prevents the inner sleeve 22 from directly contacting the user's skin / applying only light pressure to the user's skin. In this way, movement of the inner sleeve does not grip the user's skin and move it against the needle 17 during needle insertion, which may cause additional pain.

[0046] The inner sleeve 22 can rotate fully or partially (i.e., with some constraint) relative to the outer sleeve 23. The inner sleeve 22 is constrained vertically relative to the outer sleeve 23. Such freedom and / or constraint may act to limit any additional force required to depress the housing 11 during use.

[0047] The housing 11 includes one or more engagement features 24 (also referred to herein as "forcing features") that are positioned to engage features on a surface of the inner sleeve 22 to transfer energy from the movement of the housing 11 to the inner sleeve 22 to rotate and / or vibrate the distraction portion 21. For example, the surface of the inner sleeve 22 may be contoured and / or include multiple ridges and / or peaks. As the one or more engagement features 24 pass over these features, friction between the one or more engagement features 24 and the surface features of the inner sleeve 22 causes the inner sleeve 22 to vibrate, thereby vibrating the distraction portion 21 of the needle sleeve 19.

[0048] Alternatively or additionally, one or more engagement features 24 may engage with one or more tracks on a surface of the needle housing 19. The tracks are on the inner sleeve 22 in embodiments where the needle sleeve 19 includes an inner sleeve 22 and an outer sleeve 23. The tracks act to guide the movement of the inner sleeve 22 relative to the housing 11 during depression of the housing. An embodiment in which the engagement portion is coupled to tracks on the inner sleeve 22 is described in further detail below with reference to Figures 5-6. In embodiments where the needle sleeve 19 is a single piece, the tracks are on a surface of the needle sleeve 19 and may cause the entire needle sleeve 19 to rotate or vibrate during depression of the housing 11.

[0049] In embodiments where there are multiple engagement portions 24, the engagement portions 24 are symmetrically arranged around the inside of the housing 11. Such an arrangement may assist in maintaining the inner sleeve in a centered position. For example, in the embodiment shown, the engagement portions 24 are arranged at radially opposed positions around the inside of the housing 11. However, the engagement portions 24 may be arranged in other symmetrical arrangements, such as an arrangement having three-fold rotational symmetry where the engagement portions 24 are arranged at 120 degree angular offsets around the inside of the housing 11, or a configuration having four-fold rotational symmetry where the engagement portions 24 are arranged at 90 degree angular offsets around the inside of the housing 11. Other conventional angular offsets of the engagement portions 24 may alternatively be used.

[0050] In some embodiments, the engagement portions 24 have symmetric angular distances around the inside of the housing 11 relative to the longitudinal axis of the housing, but are offset laterally / longitudinally. Such an arrangement results in a discrete screw-like symmetry in the engagement portions 24. For example, the second engagement portion is positioned at an angular offset of 120 degrees relative to the first engagement portion, but is offset laterally. The third engagement portion is positioned at an angular offset of 120 degrees relative to the second engagement portion, but is offset laterally. Thus, the engagement portions 24 are symmetrically positioned in their angular coordinates, but are displaced in the longitudinal direction. Such an arrangement is beneficial for keeping the needle housing 19 centered when the needle housing has a single track on its surface.

[0051] 4a-c show examples of surface patterns at the distal end of the distraction portion of an injection device. In some embodiments, the distraction portion 21 of the needle sleeve 19 may include one or more surface features 25a-c arranged to provide sensory stimulation to the area around the injection site when the distraction portion vibrates and / or rotates. The protrusions 25a-c may contact the user's skin during vibration / rotation of the distraction portion 21 to provide a distraction sensation to the user.

[0052] In some embodiments, the surface features 25a-c are positioned such that the outer sleeve 23 of the needle sleeve 19 extends slightly beyond the surface features 25a-c. During use, the surface features 25a-c then lightly contact the user's skin in the area of ​​injection, thereby providing a distraction sensation without adversely affecting the depression of the housing 11 during use, or gripping or moving the user's skin during needle 17 insertion. In other words, the surface features 25a-c apply only light pressure to the user's skin during vibration and / or rotation of the distraction portion 21.

[0053] The surface features may include one or more protrusions from the surface of the attention diversion portion 21. The protrusions may include, for example, a plurality of ridges 25a on the surface of the attention diversion portion 21, as shown in FIG. 4a. The ridges 25a are regularly or irregularly spaced on the surface of the attention diversion portion 21. The plurality of ridges 25a may have a regular or irregular shape. The protrusions may alternatively or additionally include apexes 25b, 25c on the surface of the attention diversion portion 21. The apexes 25b are inclined towards or away from the direction of rotation of the attention diversion portion, as shown in FIG. 4b. Alternatively, the apexes 25c are aligned radially, as shown in FIG. 4c.

[0054] In some embodiments (not shown), the distraction portion 21 includes one or more distally extending brushes. The brushes extend slightly beyond the outer sleeve 23 of the needle sleeve 19 and may bend when under pressure. During rotation and / or vibration of the distraction portion 21, the brushes provide a "tickling" sensation to distract the user from the pain of the needle 17 penetrating the skin.

[0055] 5 shows a cutaway view of an embodiment of an injection device 50. In some embodiments, one or more engagement features on the housing 11 are positioned to engage with one or more recessed tracks 26 on a surface of the inner sleeve 22 of the needle housing. During depression of the housing 11 in the distal direction, the one or more engagement portions 24 ride within the tracks 26 on the inner sleeve 26, transferring force / energy from the housing 11 to the inner sleeve 22 to vibrate and / or rotate the distraction portion.

[0056] The characteristics of the one or more tracks 26 are tailored to provide different effects on the movement of the inner sleeve 22 / attention distraction portion 21. In some embodiments, the one or more tracks 26 may extend around the inner sleeve 22 in a spiral. The engagement feature 24 then causes the inner sleeve 22 to rotate when the housing 11 is pressed down. In some embodiments, the one or more tracks 26 are in the form of a zigzag on the surface of the inner sleeve 22. The engagement feature 24 then causes the inner sleeve 22 to oscillate / vibrate when the housing 11 is pressed down. The one or more tracks 26 are a combination of a spiral and a zigzag to provide both a rotational and a vibrational movement to the inner sleeve 22 / attention distraction portion 21 when the housing 11 is pressed down.

[0057] In some embodiments, multiple engagement portions 24 are received in the tracks 26. Multiple tracks 26 may be present on the surface of the inner sleeve 22, each coupled to one or more different engagement portions 24. These features may help stabilize the injection device 50 during use.

[0058] In some embodiments, the engagement portion includes a ratchet device configured to resist movement of the needle sleeve between the extended and retracted positions and not resist movement of the needle sleeve between the retracted and extended positions. The engagement portion 24 is hinged such that it folds when the housing 11 is displaced proximally relative to the needle housing 19 (i.e., when the needle housing 19 is moving between the retracted and extended positions) but extends and remains engaged with the needle sleeve 19 when the housing 11 is displaced distally relative to the needle housing 19 (i.e., when the needle housing 19 is moving between the extended and retracted positions). This can reduce resistance during retraction of the needle 17 from the body.

[0059] Figures 6a-c show examples of tracks 26a-c for use on needle housing 19. By varying the shape of tracks 26, different sensations are achieved on the user's skin. In the example shown, needle sleeve 19 includes inner sleeve 22 and outer sleeve 23 having tracks 26a-c. However, the tracks may alternatively form part of a single needle sleeve 19.

[0060] 6a shows an oscillating track 26a on the surface of the inner sleeve 22. The oscillating track 26a provides a substantially smooth "wavy" track on the inner sleeve 22. When the housing 11 is pressed down, an engagement feature 24 (not shown) of the housing 11 that is coupled to the track 26a causes the inner sleeve 22 to oscillate about the longitudinal axis AA. In some embodiments, a single oscillating track 26a is provided. Alternatively, two or more oscillating tracks 26a are provided, offset about the longitudinal axis AA.

[0061] 6b shows a helical track 26b on the surface of the inner sleeve 22. The helical track 26b extends around the inner sleeve 22. When the housing 11 is pressed down, an engagement feature 24 (not shown) on the housing 11 that is coupled to the track 26b causes the inner sleeve 22 to rotate. In some embodiments, a single helical track 26b is provided. Alternatively, two or more offset helical tracks 26b are provided.

[0062] 6c shows a zigzag track 26c on the surface of the inner sleeve 22. The zigzag track 26c provides a steep stepped track on the inner sleeve 22. When the housing 11 is pressed down, an engagement feature 24 (not shown) of the housing 11 that is coupled to the track 26c causes the inner sleeve 22 to rapidly vibrate / oscillate about the longitudinal axis AA. In some embodiments, a single zigzag track 26c is provided. Alternatively, two or more zigzag tracks 26c are provided, offset about the longitudinal axis AA.

[0063] In some embodiments, the vibrating and / or rotating portion may include one or more piezoelectric devices. Movement of the injection device between the first and second configurations may cause the piezoelectric devices to generate electricity that causes the vibrating and / or rotating portion to vibrate and / or rotate. Alternatively or additionally, the generated electricity is used to deliver a mild shock to the patient's skin to distract the patient from the sensation of the needle penetrating the skin.

[0064] The embodiments of the injection devices described herein are configured to receive either a drug cartridge or a drug pre-filled syringe. As used herein, the term "drug container" is intended to encompass both drug cartridges and pre-filled syringes.

[0065] The term "drug" or "medicament" is used herein to describe one or more pharmacologic active compounds. As described below, a drug or medicament may include at least one small molecule or macromolecule or combinations thereof in various types of formulations for the treatment of one or more diseases. Exemplary pharmacologic active compounds may include small molecules, polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes), carbohydrates and polysaccharides, as well as nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids can be incorporated into vectors, plasmids, or molecular delivery systems such as liposomes. Mixtures of one or more of these drugs are also contemplated.

[0066] The term "drug delivery device" is intended to encompass any type of device or system configured to administer a drug to a human or animal body. Without limitation, the drug delivery device may be an injection device (e.g., a syringe, pen injector, auto-injector, large volume device, pump, perfusion system, or other device configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), a skin patch (e.g., osmotic, chemical, microneedle), an inhaler (e.g., nasal or pulmonary), an implant (e.g., coated stent, capsule), or a delivery system for the gastrointestinal tract. The drugs described herein may be particularly useful in injection devices that include a needle, e.g., a small gauge needle.

[0067] The drug or agent can be contained in a primary package or "drug container" adapted for use in a drug delivery device. The drug container can be, for example, a cartridge, syringe, reservoir, or other vessel configured to provide a chamber suitable for storage (e.g., short-term or long-term storage) of one or more pharma- ceutically active compounds. For example, in some cases, the chamber can be designed to store the drug for at least one day (e.g., from one day to at least 30 days). In some cases, the chamber can be designed to store the drug for about one month to about two years. Storage can be at room temperature (e.g., about 20° C.) or at refrigerated temperatures (e.g., from about −4° C. to about 4° C.). In some cases, the drug container can be or include a dual-chamber cartridge configured to separately store two or more components of a drug formulation (e.g., a drug and a diluent, or two different types of drugs), one in each chamber. In such cases, the two chambers of the dual-chamber cartridge can be configured to allow mixing between two or more components of a drug or agent prior to and / or during administration to the human or animal body. For example, the two chambers can be configured to be in fluid communication with each other (e.g., via a conduit between the two chambers) and to allow mixing of the two components by a user, if desired, prior to administration. Alternatively or additionally, the two chambers can be configured to allow mixing upon administration of the components to the human or animal body.

[0068] The drug delivery devices and drugs according to the present invention can be used for the treatment and / or prevention of many different types of disorders. Exemplary disorders include, for example, diabetes or complications associated with diabetes, such as diabetic retinopathy, thromboembolic disorders, such as deep vein thromboembolism or pulmonary thromboembolism. Further exemplary disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis.

[0069] Exemplary drugs for the treatment and / or prevention of diabetes or complications associated with diabetes include insulin, e.g., human insulin, or a human insulin analog or derivative, glucagon-like peptide (GLP-1), a GLP-1 analog or GLP-1 receptor agonist, or an analog or derivative thereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or a pharma- ceutically acceptable salt or solvate thereof, or any mixture thereof. As used herein, the term "derivative" refers to any substance that is sufficiently structurally similar to the original substance so as to have substantially the same functionality or activity (e.g., therapeutic effect).

[0070] Exemplary insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin in which the proline at position B28 is replaced by Asp, Lys, Leu, Val or Ala and Lys at position B29 may be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0071] Exemplary insulin derivatives include, for example, B29-N-myristoyl-des(B30) human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl-LysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin; B30-N-myristoyl-ThrB29Lys B30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1 analogs and GLP-1 receptor agonists include, for example, lixisenatide / AVE0010 / ZP10 / Lyxumia, exenatide / exendin-4 / Byetta / Bydureon / ITCA650 / AC-2993 (a 39 amino acid peptide produced by the salivary glands of the flathead monster), liraglutide / Victoza, semaglutide, taspoglutide, synclear / albiglutide, dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langrena These include: cefotide / HM-11260C, CM-3, GLP-1 Erigen, ORMD-0901, NN-9924, NN-9926, NN-9927, nodexene, Viadol-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, exenatide-XTEN and glucagon-Xten.

[0072] An exemplary oligonucleotide is, for example, the cholesterol-lowering antisense therapeutic mipomersen / quinamro for the treatment of familial hypercholesterolemia.

[0073] Exemplary DPP4 inhibitors are vidagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

[0074] Exemplary hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, lutropin, chorion gonadotropin, menotropin), somatropine (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin, and goserelin.

[0075] Exemplary polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or very low molecular weight heparin or derivatives thereof, or sulfated polysaccharides, such as the above-mentioned polysaccharides in polysulfated form, and / or their pharmaceutically acceptable salts.An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium.An example of a hyaluronic acid derivative is Hylan G-F20 / Synvisc, sodium hyaluronate.

[0076] The term "antibody" as used herein refers to an immunoglobulin molecule or an antigen-binding portion thereof. Examples of antigen-binding portions of an immunoglobulin molecule include F(ab) and F(ab')2 fragments that retain the ability to bind to an antigen. The antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (e.g., murine) antibody, or a single chain antibody. In some embodiments, the antibody has effector function and is capable of fixing complement. In some embodiments, the antibody has reduced or no binding ability to Fc receptors. For example, the antibody can be an isotype or subtype, an antibody fragment, or a mutant that does not support binding to Fc receptors, e.g., has a mutation or deletion of the Fc receptor binding region.

[0077] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., antibody heavy and / or light chain polypeptide) derived from an antibody polypeptide molecule that does not include the full-length antibody polypeptide but comprises at least a portion of the full-length antibody polypeptide that is still capable of binding to an antigen. An antibody fragment may include truncated portions of a full-length antibody polypeptide, but the term is not limited to such truncated fragments. Antibody fragments useful in the present invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments, such as bispecific, trispecific, and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), minibodies, chelating recombinant antibodies, tribodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

[0078] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences in the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences in the variable regions of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the proper arrangement of CDR sequences to allow antigen binding. Although framework regions themselves typically do not directly participate in antigen binding, as is known in the art, certain residues in the framework regions of a particular antibody may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDR to interact with an antigen.

[0079] Exemplary antibodies are anti-PCSK-9 mAbs (e.g., alirocumab), anti-IL-6 mAbs (e.g., sarilumab), and anti-IL-4 mAbs (e.g., dupilumab).

[0080] The compounds described herein can be used in pharmaceutical preparations that include (a) the compounds or their pharmaceutically acceptable salts, and (b) pharmaceutically acceptable carriers.The compounds can also be used in pharmaceutical preparations that include one or more other active pharmaceutical ingredients, or in pharmaceutical preparations in which the compounds or their pharmaceutically acceptable salts are the only active ingredient.Thus, the pharmaceutical preparations of the present disclosure encompass any preparation made by mixing the compounds described herein with a pharmaceutically acceptable carrier.

[0081] Pharmaceutically acceptable salts of any of the drugs described herein are contemplated for use in the drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and base salts. Acid addition salts are, for example, HCl or HBr salts. Base salts are, for example, salts with a cation selected from an alkali or alkaline earth metal, for example, Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), where R1 to R4 are each independently: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharma-ceutically acceptable salts are known to those skilled in the art.

[0082] Pharmaceutically acceptable solvates are, for example, hydrates or alkanolates, such as methanolates or ethanolates.

[0083] Those skilled in the art will understand that modifications (addition and / or removal) of the various components of the materials, formulations, devices, methods, systems, and embodiments described herein may be made without departing from the full scope and spirit of the invention, which encompasses such modifications and any and all equivalents thereof.

Claims

1. 1. An injection device comprising: an elongate housing having a proximal end and a distal end and configured to receive a container of a medicament; a needle housing for holding a needle in position at a distal end of the elongate housing; a needle sleeve mounted within the elongated housing; Including, wherein the needle sleeve and the needle housing are user-operated movable relative to one another between a first configuration in which the needle sleeve surrounds a needle held in the needle holder and a second configuration in which the needle held in the needle housing extends distally from the needle sleeve; the needle sleeve includes a portion configured to vibrate using energy from a user manipulation during movement between the first configuration and the second configuration; the needle sleeve includes an outer sleeve and an inner sleeve, the inner sleeve including a portion configured to vibrate; the inner sleeve includes one or more recessed tracks; the elongated housing includes one or more engagement portions disposed to couple with the one or more tracks to induce oscillation of the inner sleeve during movement of the needle sleeve between the extended position and the retracted position; the one or more tracks are in a zigzag configuration on a surface of the inner sleeve, thereby causing the inner sleeve to oscillate during movement between the first and second configurations; The injection device.

2. In the first configuration, the needle sleeve is in an extended position in which the needle sleeve extends at least partially from the distal end of the elongate housing; 2. The injection device of claim 1, wherein in the second configuration, the needle sleeve is in a retracted position in which the needle sleeve is received deeper within the elongate housing than in the extended position.

3. 3. The injection device of claim 2, wherein the needle housing is substantially fixed relative to the elongate housing such that when the needle sleeve is in the extended position, the needle is concealed and when the needle sleeve is in the retracted position, the needle is exposed.

4. An injection device according to any one of claims 1 to 3, wherein the outer sleeve extends distally beyond the inner sleeve.

5. 2. The injection device of claim 1, wherein the one or more engagement portions include a ratchet arrangement configured to resist movement between the first and second configurations and not resist movement between the second and first configurations.

6. An injection device as described in any one of claims 1 to 5, wherein the portion of the needle sleeve configured to vibrate includes one or more distally extending brushes, one or more distally extending protrusions and / or peaks, and / or one or more piezoelectric devices.

7. a piston rod longitudinally movable within the elongated housing; a piston spring configured to bias the piston rod toward a distal end of the elongated housing to engage a container of medicament when received within the elongated housing; Further comprising: An injection device according to any one of claims 1 to 6, wherein the needle sleeve is configured to suppress vibrations of the part during longitudinal movement of the piston rod in the distal direction.

8. a piston rod longitudinally movable within the elongated housing; a piston spring configured to bias the piston rod toward a distal end of the elongated housing to engage a container of medicament when received within the elongated housing; Further comprising: An injection device according to any one of claims 1 to 7, wherein the portion of the needle sleeve configured to vibrate is further configured to vibrate during longitudinal movement of the piston rod in the distal direction.

9. The needle sleeve is fixed relative to the elongated housing: In a first configuration, the needle housing is in a retracted position in which the needle retained within the needle housing is obscured by the needle sleeve; An injection device according to any one of claims 1 to 8, wherein in the second configuration the needle housing is in an extended position in which the needle within the needle housing extends distally beyond the needle sleeve.

10. 10. An injection device according to any one of claims 1 to 9, further comprising a needle for expelling medicament from the injection device, the needle being held at a position at a distal end of the elongate housing that is substantially fixed relative to the elongate housing such that the needle is concealed when the needle sleeve is in the extended position and exposed when the needle sleeve is in the retracted position.

11. A method for operating an injection device according to any one of claims 1 to 10, comprising the steps of: Providing an injection device in a first configuration; and changing a configuration of the user device from a first configuration to a second configuration by application of a user action.

12. A method of actuating an injection device according to any one of claims 1 to 11, the injection device having a distal end and a proximal end, the distal end including a needle sleeve and a needle, the method comprising: moving, under user manipulation, the injection device between a first configuration in which the needle sleeve surrounds the needle and a second configuration in which the needle extends distally beyond the needle sleeve; and vibrating a portion of the distal end of the injection device during movement between the first and second configurations using energy from a user manipulation.

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