Injection device with attention diverting mechanism

Abstract

The present disclosure relates to features of an injection device arranged to provide a sensory distraction to a user during insertion of a needle into the skin. According to a first aspect, the present specification discloses an injection device comprising: an elongated housing having a proximal end and a distal end and being configured to receive a medicament container; a needle housing for holding a needle in position at the distal end of the elongated housing; and a needle sleeve mounted within the housing, wherein the needle sleeve and needle housing are movable relative to each other between a first configuration in which the needle sleeve will enclose a needle held in a needle holder and a second configuration in which a needle held in the needle housing will protrude from the needle sleeve in a distal direction, wherein the needle sleeve comprises a portion configured to vibrate and / or rotate during movement between the first configuration and the second configuration using energy from the user action.

Description

Technical Field

[0001] This disclosure relates to features of an injection device arranged to provide a sensory distraction to the user during needle insertion into the skin. Background Technology

[0002] Injection devices (such as autoinjectors) are known in the art for dispensing medications to a patient's injection site. Such devices typically include a body and a cap, a syringe with a needle located within the body, and the cap is removably attached to the body to protect the needle of the syringe. To dispense medication, the cap is first removed from the body to expose the needle. The needle is then inserted into the patient at the injection site to dispense the medication.

[0003] Inserting a needle into a user's body is typically associated with pain and discomfort. Additionally, users may become anxious and tense during needle insertion, leading to additional pain. Summary of the Invention

[0004] According to a first aspect, this specification discloses an injection device comprising: an elongated housing having a proximal end and a distal end, and configured to receive a drug container; a needle housing for holding a needle in 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 between a first configuration and a second configuration by a user action, in the first configuration the needle sleeve surrounds a needle held in a needle holder, and in the second configuration the needle held in the needle housing extends distally from the needle sleeve, wherein the needle sleeve includes a portion configured to vibrate and / or rotate using energy from the user action during movement between the first and second configurations.

[0005] In the 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 the second configuration, the needle sleeve can be in a retracted position, in which the needle sleeve is received further within the housing than in the extended position. The needle housing can be substantially fixed relative to the elongated housing such that the needle is shielded when the needle sleeve is in the extended position and exposed when the needle sleeve is in the retracted position.

[0006] The needle sleeve may include an outer sleeve and an inner sleeve, the inner sleeve including the portion configured for vibration and / or rotation. The outer sleeve may extend beyond the inner sleeve in the distal direction.

[0007] The inner sleeve may include one or more recessed tracks. The housing may include one or more engagement portions arranged to engage with the one or more tracks to induce vibration and / or rotation of the inner sleeve during movement of the needle sleeve between the extended position and the retracted position. The one or more tracks may extend helically about the inner sleeve, wherein the inner sleeve is free to rotate relative to the elongated housing. The one or more tracks may be in a zigzag pattern on the surface of the inner sleeve, thereby causing the inner sleeve to vibrate during movement between the first configuration and the second configuration. The one or more engagement portions may include a ratchet arrangement configured to resist movement between the first configuration and the second configuration but not to resist movement between the second configuration and the first configuration.

[0008] The user's action may include manually pressing down the elongated housing laterally in the distal direction.

[0009] The portion of the needle sleeve configured for vibration and / or rotation may include one or more brushes extending in the distal direction. The portion of the needle sleeve configured for vibration and / or rotation may alternatively or additionally include one or more protrusions and / or ridges extending in the distal direction. The portion of the needle sleeve configured for vibration and / or rotation may alternatively or additionally include one or more piezoelectric elements.

[0010] The injection device may further include: a piston rod capable of longitudinal movement within the housing; and a piston spring configured to bias the piston rod toward a distal end of the housing to engage the drug container when received within the housing;

[0011] The needle sleeve is configured to suppress vibration and / or rotation of the portion during longitudinal movement of the piston rod in the distal direction.

[0012] The injection device may further include: a piston rod capable of longitudinal movement within the housing; and a piston spring configured to bias the piston rod toward a distal end of the housing to engage a drug container when received within the housing, wherein the portion of the needle sleeve configured for vibration and / or rotation is further configured to vibrate and / or rotate during longitudinal movement of the piston rod in the distal direction.

[0013] The needle sleeve can be fixed relative to the elongated housing. In the first configuration, the needle housing can be in a retracted position, in which the needle held in the needle housing is shielded by the needle sleeve. In the second configuration, the needle housing can be in an extended position, in which the needle in the needle housing extends beyond the needle sleeve in the distal direction.

[0014] The injection device may further include a needle for dispensing a drug from the injection device, the needle being held in a position at the distal end of the elongated housing, the position being substantially fixed relative to the elongated housing such that the needle is shielded when the needle sleeve is in the extended position and exposed when the needle sleeve is in the retracted position.

[0015] The injection device may also include a pharmaceutical container received within the housing.

[0016] According to another aspect, this specification discloses a method of using the injection device, the method comprising: preparing the injection device in a first configuration; and applying a user action to change the configuration of the injection device from the first configuration to the second configuration.

[0017] According to another aspect, this specification discloses a method for inducing vibration and / or rotation of a portion of an injection device having a distal end and a proximal end, the distal end including a needle sleeve and a needle, the method comprising: moving the injection device between a first configuration and a second configuration under a user action, wherein in the first configuration the needle sleeve surrounds the needle, and in the second configuration the needle extends distally beyond the needle sleeve; and using energy from the user action during the movement between the first configuration and the second configuration to vibrate and / or rotate a portion of the distal end of the injection device. Attached Figure Description

[0018] The embodiments will now be described by way of non-limiting example with reference to the accompanying drawings, wherein:

[0019] Figures 1a and 1b illustrate exemplary drug delivery devices;

[0020] Figure 2 shows a view of an example of the distal end of the injection device;

[0021] Figure 3 shows a cross-sectional view of an embodiment of the injection device;

[0022] Figures 4a-c show examples of surface patterns at the distal end of the attention-transfer section of the injection device;

[0023] Figure 5 shows a cross-sectional view of an embodiment of the injection device; and

[0024] Figures 6a-c show examples of tracks used on the inner sleeve of the needle housing. Detailed Implementation

[0025] As described herein, drug delivery devices can be configured to inject medication into a patient. Delivery can be subcutaneous, intramuscular, or intravenous. Such devices can be operated by a patient or caregiver (such as a nurse or physician) and can include various types of safety syringes, pen syringes, or auto-injectors. The devices may include cartridge-based systems that require piercing a sealed ampoule before use. The volume of medication delivered using these different devices can range from about 0.5 ml to about 3 ml. Another device may include a high-volume device (“LVD”) or patch pump 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 may include a pre-filled syringe within the housing of the device. The syringe may be fixed within the housing or may be movable within the housing, for example, from a retracted position to an extended operating position.

[0026] In combination with specific medications, the device described herein can also be customized to operate within required specifications. For example, the device can be customized to inject the medication over a specific time period (e.g., approximately 3 to 20 seconds for an autoinjector and approximately 10 to 60 minutes for an LVD). Other specifications may include low or minimal levels of discomfort, or certain conditions related to human factors, shelf life, expiration date, biocompatibility, environmental factors, etc. This variation can occur due to various factors, such as the viscosity of the medication, which varies from approximately 3 cP to approximately 50 cP. Therefore, drug delivery devices will typically include hollow needles ranging in size from approximately 25 to approximately 31 gauges. Common sizes are 17 and 29 gauges.

[0027] The delivery device described herein may also include one or more automated functions. For example, one or more of the following processes may be automated: needle and cartridge assembly, needle insertion, drug injection, and needle retraction. Energy for one or more automated steps may be provided by one or more energy sources. Energy sources may include, for example, mechanical energy, pneumatic energy, chemical energy, or electrical energy. For example, a mechanical energy source may include a spring, lever, elastomer, or other mechanical mechanism that stores or releases energy. One or more energy sources may be combined into a single device. The device may also include gears, valves, or other mechanisms that convert energy into movement of one or more components of the device.

[0028] The one or more automated functions of an autoinjector can each be activated via an activation mechanism. This activation mechanism may include actuators, such as buttons, levers, needle sleeves, or other activating components. Activation of the automated function can be a one-step or multi-step process. That is, the user may need to activate one or more activation components to produce the automated function. For example, in a one-step process, the user may press down on the needle sleeve against their body to induce injection of the drug. Other devices may require multi-step activation of the automated function. For example, the user may need to press a button and retract the needle sheath to induce injection.

[0029] Furthermore, activation of one automated function can activate one or more subsequent automated functions, thus forming an activation sequence. For example, activation of the first automated function can activate at least two of the following: needle and cartridge assembly, needle insertion, drug injection, and needle retraction. Some devices may also require a specific sequence of steps to cause the one or more automated functions to occur. Other devices may operate in a series of independent steps.

[0030] Some delivery devices may include one or more functions of a safety syringe, pen syringe, or autoinjector. For example, a delivery device may include a mechanical power source configured to automatically inject the drug (as typically found in autoinjectors) and a dosage setting mechanism (as typically found in pen syringes).

[0031] According to some embodiments of this disclosure, an exemplary drug delivery device 10 is shown in Figures 1A and 1B. As described above, device 10 is configured to inject a drug into a patient. Device 10 includes a housing 11 that typically contains a cartridge or pre-filled syringe defining a reservoir containing the drug to be injected, and components necessary to facilitate one or more steps of the delivery process.

[0032] The device 10 may also include a cap 12 that can be detachably mounted to the housing 11. Typically, the user must remove the cap 12 from the housing 11 before the device 10 can be operated.

[0033] As shown in the figure, the shell 11 is generally cylindrical and has a substantially constant diameter along the longitudinal axis AA. The shell 11 has a distal region D and a proximal region P. The term "distal" refers to the location relatively closer to the injection site, and the term "proximal" refers to the location relatively farther away from the injection site.

[0034] The device 10 may also include a needle sleeve 19 coupled to the housing 11 to allow the sleeve 19 to move relative to the housing 11. For example, the sleeve 19 may be movable in a longitudinal direction parallel to the longitudinal axis AA. Specifically, movement of the sleeve 19 in the proximal direction may allow the needle 17 to extend from the distal region D of the housing 11. In some embodiments, the needle sleeve 19 may alternatively be fixed relative to the housing 11 or formed as part of the housing 11.

[0035] Insertion of the needle 17 can occur via several mechanisms. For example, the needle 17 can be fixedly positioned relative to the housing 11 (e.g., within a needle housing (not shown)) and initially located within an extended needle sleeve 19. Proximal movement of the sleeve 19 by placing it against the patient's body and moving the housing 11 in a distal direction exposes the distal end of the needle 17. This relative movement allows the distal end of the needle 17 to extend into the patient's body. This insertion is referred to as "manual" insertion because the needle 17 is manually inserted by the patient manually moving the housing 11 relative to the sleeve 19.

[0036] Another form of insertion is "automatic," whereby the pin 17 moves relative to the housing 11. This insertion can be triggered by movement of the sleeve 19 or by another form of activation (such as button 13). As shown in Figures 1A and 1B, button 13 is located at the proximal end of the housing 11. However, in other embodiments, button 13 may be located on one side of the housing 11.

[0037] Other manual or automated features may include drug injection or needle retraction, or both. Injection is the process by which the stopper or piston 14 moves from a proximal position to a more distal position within the reservoir of cartridge 18 to force the drug out of cartridge 18 through needle 17. In some embodiments, a drive spring (not shown) is compressed before device 10 is activated. The proximal end of the drive spring may be fixed within a proximal region P of housing 11, and the distal end of the drive spring may be configured to apply a compressive force to the proximal surface of piston 14 (also referred to as a “plunger”). Upon activation, at least a portion of the energy stored in the drive spring can be applied to the proximal surface of piston 14. This compressive force can act on piston 14 to move it in a distal direction. This distal movement is used to compress the liquid drug within cartridge 18, thereby forcing it out of needle 17. This distal movement may be referred to as “pressing down” piston 14.

[0038] After injection, the needle 17 can retract into the sleeve 19 or the housing 11. Retraction can occur when the user removes the device 10 from the patient's body, as the sleeve 19 moves distally. This can happen while the needle 17 remains fixedly positioned relative to the housing 11. Once the distal end of the sleeve 19 has moved past the distal end of the needle 17 and the needle 17 is covered, the sleeve 19 can be locked. This locking can include locking any proximal movement of the sleeve 19 relative to the housing 11.

[0039] Another form of needle retraction can occur if the needle 17 moves relative to the housing 11. This movement can occur if the cartridge 18 within the housing 11 moves proximally relative to the housing 11. This proximal movement can be achieved using a retraction spring (not shown) located in the distal region D. A compressed retraction spring, when activated, can provide sufficient force to the cartridge 18 to move it proximally. After full retraction, any relative movement between the needle 17 and the housing 11 can be locked by a locking mechanism. Additionally, the button 13 or other components of the device 10 can be locked as needed.

[0040] In some implementations, the injection device can be a needle-free device, such as a jet injector. In this type of device, there is no needle. The medication is administered by expelling it from the injection device as a high-pressure fluid stream that penetrates the recipient's skin.

[0041] Figure 2 shows a view of an example of the distal end of the injection device. The distal end 20 of the injection device includes a needle sleeve 19, which includes a portion 21 (also referred to herein as an “attention-diverting portion”) configured to vibrate and / or rotate during movement between an extended position and a retracted position. The needle sleeve 19 is arranged to shield (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 shields the needle may be referred to herein as the “first configuration”, and the configuration in which the needle is exposed may be referred to herein as the “second configuration”. In Figure 2, the needle sleeve 19 is in the extended position (i.e., the first configuration).

[0042] The user actuates / moves the needle sleeve 19 between an extended position and a retracted position. The needle sleeve 19 is configured to use energy from the user actuation / movement to cause vibration and / or rotation of the attention diversion section 21, thereby allowing the needle 17 to enter the skin and flesh to provide sensory attention diversion.

[0043] For example, when performing an injection, the user places the distal end of the extended needle sleeve 19 onto the target injection site on the skin. The user applies force to the housing 11 in the distal direction, for example by grasping the housing and pushing it toward the injection site, causing the housing 11 to move laterally toward the injection site. This action is referred to herein as “pressing down” the housing. As the housing 11 moves laterally, the needle sleeve 19 retracts into the housing 11. With the needle 17 fixed relative to the housing, the needle 17 extends from the needle sleeve 19 and pierces the skin at the injection site during this movement of the housing.

[0044] During the retraction of the needle sleeve 19 into the housing, the attention-diverting portion 21 provides sensory stimulation in the area of ​​the injection site through vibration and / or rotation. The energy required to provide this vibration / rotation is extracted from the downward pressure of the housing 11. For example, a ridge within the needle sleeve 19 / attention-diverting portion 21 may rub / vibrate against the inner surface of the housing 11 to generate a vibratory sensation during downward pressure to mask the pain of needle 17 insertion. Other examples of how vibration / rotation of the attention-diverting portion 21 can be provided will be described below.

[0045] In some embodiments, such as the one shown in FIG2, the attention transfer portion 21 is provided by one or more rings at the distal end of the needle sleeve 19, said one or more rings being configured to rotate and / or oscillate during the depressurization of the housing 11. The one or more rings / attention transfer portions 21 may be positioned such that they are not under pressure during the depressurization of the housing 11, i.e., they do not directly contact the skin at the injection site, even under high pressure.

[0046] In addition to vibration / rotation during the retraction of the needle housing 19, in some embodiments, the attention-diverting portion 21 may also vibrate and / or rotate during the injection itself (i.e., during the pressing of the plunger / stopper / piston into the drug cartridge). The plunger / piston may engage with the needle sleeve 19 to use the energy from the plunger press to cause vibration / rotation of the needle sleeve 19. The needle sleeve 19 may be provided with internal features that engage with the plunger / piston to provide vibration / rotation. For example, the inner side of the needle sleeve 19 may be rough and in contact with the piston / plunger, such that movement of the piston / plunger causes vibration of the needle sleeve 19. Alternatively, the needle sleeve may have internal tracks that engage with features on the piston / plunger in a manner similar to those on the housing 11. This can divert the user's attention throughout the injection process (i.e., from needle insertion to the end of drug delivery).

[0047] In other embodiments, the needle sleeve 19 is configured not to rotate / vibrate during the depressing of the piston into the medication cartridge. This prevents the needle 17 from being moved during medication dispensing, which could cause additional pain.

[0048] In some embodiments, the needle sleeve 19 may be fixed relative to the housing 11, wherein the needle housing is movable relative to the housing 11 between a position in which the needle 17 held in the needle housing is shielded by the needle sleeve 19 (i.e., the first configuration) and a position in which the needle 17 held in the needle housing extends distally beyond the needle sleeve 19 (i.e., the second configuration). The portion of the needle sleeve 19 configured to vibrate and / or rotate utilizes energy from the user's movements during movement between the first and second configurations.

[0049] Generally, the relative movement between the needle sleeve 19 and the needle housing can be used to move between a first configuration in which the needle 17 held by the needle housing is shielded 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 movement is used to vibrate and / or rotate a portion of the needle sleeve 19 to divert attention. One of the needle sleeve 19 and the needle housing may be fixed relative to the housing 11. Alternatively, both the needle sleeve 19 and the needle housing may be movable relative to the housing 11.

[0050] In needle-free injection devices, vibrating and / or rotating portions 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 attention diversion during the penetration of the high-pressure drug flow through the skin. Mechanisms for generating the high-pressure drug flow may also be used to power the vibration and / or rotation of the vibrating and / or rotating portions. Alternatively, the vibrating and / or rotating portions may be powered independently.

[0051] Figure 3 shows a cross-sectional view of an embodiment of the 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 an attention-transfer portion 21, which is a portion configured to vibrate and / or rotate during the depressurization of the housing 11. The outer sleeve 23 may extend further distally than the inner sleeve 22, such that the outer sleeve 23 will contact the user's skin during use and prevent the inner sleeve 22 from directly contacting the user's skin / applying only slight pressure to the user's skin. In this way, the movement of the inner sleeve will not clamp the user's skin and move it relative to the needle 17 during needle insertion, which could cause additional pain.

[0052] The inner sleeve 22 can rotate freely relative to the outer sleeve 23, either fully or partially (i.e., within certain limitations). The inner sleeve 22 can be constrained vertically relative to the outer sleeve 23. This freedom and / or constraint can serve to limit any additional forces required to press down on the housing 11 during use.

[0053] The housing 11 includes one or more engagement features 24 (also referred to herein as “force-applying features”) arranged to engage with features on the surface of the inner sleeve 22 to transfer energy from the movement of the housing 11 to the inner sleeve 22, causing the attention-transfer portion 21 to rotate and / or vibrate. For example, the surface of the inner sleeve 22 may be rough and / or include multiple ridges and / or protrusions. As the one or more engagement features 24 pass over these features, the 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 causing the attention-transfer portion 21 of the needle sleeve 19 to vibrate.

[0054] Alternatively or additionally, the one or more engagement features 24 may engage with one or more tracks on the surface of the needle housing 19. In embodiments where the needle sleeve 19 comprises an inner sleeve 22 and an outer sleeve 23, the tracks may be on the inner sleeve 22. The tracks are used to guide the movement of the inner sleeve 22 relative to the housing 11 during the depressurization of the housing. An embodiment in which the engagement portion is coupled to the tracks on the inner sleeve 22 is described in more detail below with reference to Figures 5 and 6. In embodiments where the needle sleeve 19 is a single piece, the tracks may be on the surface of the needle sleeve 19 and cause the entire needle sleeve 19 to rotate or vibrate during the depressurization of the housing 11.

[0055] In embodiments where multiple joining portions 24 are present, the joining portions 24 may be arranged symmetrically about the inner side of the housing 11. This arrangement can help keep the inner sleeve in a central position. For example, in the illustrated embodiment, the joining portions 24 are arranged at radially opposite positions on the inner side of the housing 11. However, the joining portions 24 may be arranged in other symmetrical configurations, such as a configuration with triple rotational symmetry, wherein the joining portions 24 are offset by an angle of 120 degrees about the inner side of the housing 11, or a configuration with quadruple rotational symmetry, wherein the joining portions 24 are offset by an angle of 90 degrees about the inner side of the housing 11. Other regular angular offsets of the joining portions 24 may also be used alternatively.

[0056] In some embodiments, the engagement portions 24 have angular intervals symmetrical about the inner side of the housing 11 with respect to the longitudinal axis of the housing, but offset in the lateral / longitudinal direction. This arrangement gives the engagement portions 24 a discontinuous, screw-like symmetry. For example, the second engagement portion may be offset by 120 degrees relative to the first engagement portion, but offset in the lateral direction. The third engagement portion may be offset by 120 degrees relative to the second engagement portion, but offset in the lateral direction. Thus, the engagement portions 24 are symmetrically arranged in their angular coordinates, but displaced in the longitudinal direction. This arrangement can be advantageous when the needle housing has a single track on its surface, allowing the needle housing 19 to remain centered.

[0057] Figures 4a-c illustrate examples of surface patterns at the distal end of the attention-transfer portion of the injection device. In some embodiments, the attention-transfer portion 21 of the needle sleeve 19 may include one or more surface features 25a-c arranged to provide sensory stimulation to an area surrounding the injection site when the attention-transfer portion vibrates and / or rotates. During vibration / rotation of the attention-transfer portion 21, protrusions 25a-c may contact the user's skin to provide the user with a sensation of attention transfer.

[0058] In some embodiments, surface features 25a-c are arranged such that the outer sleeve 23 of the needle sheath 19 extends only slightly beyond surface features 25a-c. Then, during use, surface features 25a-c will make only slight contact with the user's skin in the injection area, thereby providing a distracting sensation without adversely affecting the downward pressure of the housing 11 or clamping and moving the user's skin during needle 17 insertion. In other words, during vibration and / or rotation of the distraction portion 21, surface features 25a-c apply only slight pressure to the user's skin.

[0059] Surface features may include one or more protrusions on the surface of the attention transfer portion 21. For example, the protrusions may include a plurality of ridges 25a on the surface of the attention transfer portion 21, as shown in FIG4a. The ridges 25a may be regularly or irregularly spaced on the surface of the attention transfer portion 21. The plurality of ridges 25a may have regular or irregular shapes. The protrusions may alternatively or additionally include ridges 25b, 25c on the surface of the attention transfer portion 21. The ridges 25b may be angled toward or away from the direction of rotation of the attention transfer portion, as shown in FIG4b. Alternatively, the ridges 25c may be aligned in the radial direction, as shown in FIG4c.

[0060] In some embodiments (not shown), the attention diversion section 21 includes one or more brushes extending in a distal direction. The brushes may extend slightly beyond the outer sleeve 23 of the needle sleeve 19 and bend under pressure. During rotation and / or vibration of the attention diversion section 21, the brushes provide a "scratching" sensation to distract the user from the pain of the needle 17 entering the skin.

[0061] Figure 5 shows a cross-sectional view of an embodiment of the injection device 50. In some embodiments, the one or more engagement features on the housing 11 are arranged to engage with one or more recessed tracks 26 on the surface of the inner sleeve 22 of the needle housing. During the downward and downward pressure of the housing 11 in the distal direction, the one or more engagement portions 24 travel within the tracks 26 on the inner sleeve 22, transferring force / energy from the housing 11 to the inner sleeve 22 to cause the attention-transfer portion to vibrate and / or rotate.

[0062] The characteristics of the one or more tracks 26 can be customized to produce different effects on the movement of the inner sleeve 22 / attention transfer portion 21. In some embodiments, the one or more tracks 26 may extend helically around the inner sleeve 22. The engagement feature 24 then causes the inner sleeve 22 to rotate as the housing 11 is pressed down. In some embodiments, the one or more tracks 26 may be in a zigzag shape on the surface of the inner sleeve 22. The engagement feature 24 then causes the inner sleeve 22 to oscillate / vibrate as the housing 11 is pressed down. The one or more tracks 26 may be a combination of helical and zigzag shapes to provide rotational and vibratory motion to the inner sleeve 22 / attention transfer portion 21 as the housing 11 is pressed down.

[0063] In some embodiments, multiple engagement portions 24 may be received in rails 26. Multiple rails 26 may exist on the surface of the inner sleeve 22, each rail being coupled to one or more different engagement portions 24. These features can help stabilize the injection device 50 during use.

[0064] In some embodiments, the engagement portion includes a ratchet arrangement configured to resist movement of the needle sleeve between an extended and retracted position, but not against movement of the needle sleeve between a retracted and extended position. The engagement portion 24 can be hinged such that it folds back when the housing 11 is displaced proximally relative to the needle housing 19 (i.e., when the needle housing 19 is moving between a retracted and extended position), but remains extended and engages 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 an extended and retracted position). This reduces resistance during the retraction of the needle 17 from the body.

[0065] Figures 6a-c show examples of tracks 26a-c used on the needle housing 19. Different sensations can be achieved on the user's skin by changing the shape of the tracks 26. In the illustrated example, the needle sleeve 19 includes an inner sleeve 22 and an outer sleeve 23, the inner sleeve having tracks 26a-c. However, the tracks can alternatively be formed as part of a single needle sleeve 19.

[0066] Figure 6a shows a swing track 26a on the surface of the inner sleeve 22. The swing track 26a provides a substantially smooth "wavy" track on the inner sleeve 22. When the housing 11 is pressed down, the engagement feature 24 (not shown) of the housing 11 connecting to the track 26a causes the inner sleeve 22 to swing about the longitudinal axis AA. In some embodiments, a single swing track 26a is provided. Alternatively, two or more swing tracks 26a offset about the longitudinal axis AA may be provided.

[0067] Figure 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, the engagement feature 24 (not shown) of the housing 11 connecting 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 may be provided.

[0068] Figure 6c shows a zigzag track 26c on the surface of the inner sleeve 22. The zigzag track 26c provides a sharp, stepped track on the inner sleeve 22. When the housing 11 is pressed down, the engagement feature 24 (not shown) of the housing 11 connecting to the track 26c causes the inner sleeve 22 to vibrate / oscillate sharply about the longitudinal axis AA. In some embodiments, a single zigzag track 26c is provided. Alternatively, two or more zigzag tracks 26c offset about the longitudinal axis AA may be provided.

[0069] In some embodiments, the vibrating and / or rotating portion may include one or more piezoelectric devices. Movement of the injection device between a first and a second configuration can generate electricity in the piezoelectric devices, which causes the vibrating and / or rotating portion to vibrate and / or rotate. Alternatively or additionally, the generated electricity can be used to apply a gentle electric shock to the patient's skin to distract them from the sensation of the needle entering the skin.

[0070] The embodiments of the injection device described herein are configured to receive a pharmaceutical cartridge or a pre-filled syringe. In this document, the term "pharmaceutical container" is intended to encompass both pharmaceutical cartridges and pre-filled syringes.

[0071] The terms "drug" or "pharmaceutical" are used herein to describe one or more pharmaceutically active compounds. As described below, a drug or pharmaceutical agent may comprise at least one small molecule or macromolecule or combination thereof in various types of formulations for the treatment of one or more diseases. Exemplary pharmaceutically active compounds may include small molecules; polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and 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 may be incorporated into molecular delivery systems (such as vectors, plasmids, or liposomes). Mixtures of one or more of these drugs are also contemplated.

[0072] The term "drug delivery device" should encompass any type of device or system configured to dispense a drug into a human or animal. Without limitation, a drug delivery device can be an injection device (e.g., syringe, pen syringe, autoinjector, bulk device, pump, infusion 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 lung), an implantable device (e.g., coated stent, capsule), or a feeding system for the gastrointestinal tract. The drugs described herein may be particularly useful when using injection devices that include needles (e.g., small-gauge needles).

[0073] The drug or pharmaceutical preparation may be contained in a primary encapsulation or "drug container" adapted for use with a drug delivery device. The drug container may be, for example, a cartridge, syringe, reservoir, or other vessel configured to provide a suitable chamber for storing (e.g., short-term or long-term storage) one or more pharmaceutically active compounds. For example, in some cases, the chamber may be designed to store the drug for at least one day (e.g., from 1 day to at least 30 days). In some cases, the chamber may be designed to store the drug for about one month to about two years. Storage may occur 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 may be or may include a dual-chamber cartridge configured to separately store two or more components of a pharmaceutical preparation (e.g., drug and diluent, or two different types of drugs), one component in each chamber. In this case, the two chambers of the dual-chamber cartridge may be configured to allow mixing of the two or more components of the drug or pharmaceutical preparation before and / or during administration to a human or animal. For example, the two chambers can be configured such that they are in fluid communication with each other (e.g., through a conduit between the two chambers) and allow the user to mix the two components when needed before dispensing. Alternatively or additionally, the two chambers can be configured to allow mixing during dispensing of the components into a human or animal body.

[0074] The drug delivery devices and drugs described herein can be used to treat and / or prevent many different types of disorders. Exemplary disorders include, for example, diabetes or diabetes-related complications (such as diabetic retinopathy) and thromboembolic disorders (such as deep vein or pulmonary thromboembolism). Other exemplary disorders include acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis, and / or rheumatoid arthritis.

[0075] Exemplary medicines for the treatment and / or prevention of diabetes or diabetes-related complications include insulin (e.g., human insulin, or human insulin analogs or derivatives); glucagon-like peptide-1 (GLP-1), GLP-1 analogs or GLP-1 receptor agonists, or analogs or derivatives thereof; dipeptidyl peptidase-4 (DPP4) inhibitors, or pharmaceutically acceptable salts or solvates thereof; or any mixtures thereof. As used herein, the term “derivative” means any substance that is structurally sufficiently similar to the original substance to have substantially similar functions or activities (e.g., therapeutic effects).

[0076] Exemplary insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (glargine insulin); Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) human insulin; Asp(B28) human insulin; human insulin wherein the proline at position B28 is replaced by Asp, Lys, Leu, Val, or Ala, and wherein the Lys at position B29 can be replaced by Pro; Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) human insulin.

[0077] 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-Thr B29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-γ-glutamyl)-des(B30) human insulin; B29-N-(N-lithochyl-γ-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 are, for example: lixumia / AVE0010 / ZP10 / Lyxumia, exenatide / Gydureon exopeptide-4 / Byetta / Bydureon / ITCA 650 / AC-2993 (a 39-amino acid peptide derived from Gila exopeptide). (produced by the salivary glands of monster), liraglutide / Victoza, semaglutide, taspoglutide, Syncria / albiglutide, Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langnatide / HM-11260C, CM-3, GLP-1Eligen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen, Viador-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.

[0078] An example oligonucleotide is, for instance, mipomersen / Kynamro, a cholesterol-reducing antisense agent used to treat familial hypercholesterolemia.

[0079] Exemplary DPP4 inhibitors include vidagliptin, sitagliptin, denagliptin, saxagliptin, and berberine.

[0080] Exemplary hormones include pituitary hormones or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotropin, fertility-stimulating hormone), growth hormone (growth hormone), desmopressin, terlipressin, gosorelin, triptorelin, leuprorelin, buserorelin, nafarelin, and goserelin.

[0081] Exemplary polysaccharides include glucosaminoglycane, hyaluronic acid, heparin, low molecular weight heparin or ultra-low molecular weight heparin or derivatives thereof, or sulfated polysaccharides (e.g., polysulfated forms of the above polysaccharides), and / or pharmaceutically acceptable salts thereof. 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 GF 20 / Synvisc, which is a sodium hyaluronate.

[0082] As used herein, the term "antibody" refers to an immunoglobulin molecule or its antigen-binding portion. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind antigens. Antibodies can be polyclonal antibodies, monoclonal antibodies, recombinant antibodies, chimeric antibodies, deimmunized or humanized antibodies, whole-human antibodies, non-human antibodies (e.g., mouse antibodies), or single-chain antibodies. In some embodiments, antibodies have effector function and can fix complement. In some embodiments, antibodies have reduced or no ability to bind to Fc receptors. For example, antibodies can be isotypes or subtypes that do not support binding to Fc receptors, antibody fragments, or mutants, for example, having a mutagenic or missing Fc receptor-binding region.

[0083] The term "fragment" or "antibody fragment" refers to a polypeptide (e.g., antibody heavy chain and / or light chain polypeptide) derived from an antibody polypeptide molecule, excluding full-length antibody polypeptides but still including at least a portion of a full-length antibody polypeptide capable of binding antigens. Antibody fragments may include cleaved portions of full-length antibody polypeptides, although the term is not limited to such cleaved fragments. Antibody fragments that can be used in this 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., double-chain, triple-chain, and quadruple-chain antibodies)), microantibodies, chelated recombinant antibodies, tri- or bispecific antibodies, intracellular antibodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camel-derived antibodies, and antibodies containing VHH. Further examples of antigen-binding antibody fragments are known in the art.

[0084] The term "complementarity-determining region" or "CDR" refers to a short polypeptide sequence within the variable region of both heavy and light chain polypeptides, primarily responsible for mediating specific antigen recognition. The term "frame region" refers to an amino acid sequence within the variable region of both heavy and light chain polypeptides; it is not a CDR sequence and is primarily responsible for maintaining the correct positioning of the CDR sequence to allow antigen binding. Although the frame region itself typically does not directly participate in antigen binding, as is known in the art, certain residues within the frame region of some antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0085] Exemplary antibodies are anti-PCSK-9 mAb (e.g., Alirocumab), anti-IL-6 mAb (e.g., Sarilumab), and anti-IL-4 mAb (e.g., Dupilumab).

[0086] The compounds described herein can be used in pharmaceutical formulations comprising (a) one or more compounds or pharmaceutically acceptable salts thereof, and (b) pharmaceutically acceptable carriers. The compounds can also be used in pharmaceutical formulations comprising one or more other active pharmaceutical ingredients, or in pharmaceutical formulations in which the compound of the present invention or a pharmaceutically acceptable salt thereof is the sole active ingredient. Therefore, pharmaceutical formulations of this disclosure cover any formulation prepared by mixing the compounds described herein with a pharmaceutically acceptable carrier.

[0087] Pharmaceutically acceptable salts of any of the drugs described herein may also be contemplated for use in drug delivery devices. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Acid addition salts are, for example, HCl salts or HBr salts. Basic salts are, for example, salts having cations selected from: alkali metals or alkaline earth metals, such as Na+, or K+, or Ca2+, or ammonium ions N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently represent: hydrogen, optionally substituted C1-C6-alkyl groups, optionally substituted C2-C6-olefin groups, optionally substituted C6-C10-aryl groups, or optionally substituted C6-C10-heteroaryl groups. Further examples of pharmaceutically acceptable salts are known to those skilled in the art.

[0088] Pharmaceutically acceptable solvates are, for example, hydrates or alkanolates, such as methanolate or ethanolate.

[0089] Those skilled in the art will understand that various modifications (additions and / or removals) can be made to various components of the substances, preparations, apparatus, methods, systems and embodiments described herein without departing from the full scope and spirit of the invention, which covers such modifications and any and all equivalents thereof.

Claims

1. An injection device, comprising: An elongated shell having a proximal end and a distal end, and configured to receive a pharmaceutical container; A needle housing for holding the needle in a position at the distal end of the elongated housing; and A needle sleeve, which is installed inside the elongated housing. The needle sleeve and needle housing are movable relative to each other between a first configuration and a second configuration by a user action. In the first configuration, the needle sleeve surrounds the needle held in the needle holder. In the second configuration, 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 the user's movements during movement between the first and second configurations. The needle sleeve includes an outer sleeve and an inner sleeve, the inner sleeve including a portion configured for vibration, wherein: The inner sleeve includes one or more recessed tracks; and The elongated housing includes one or more engagement portions arranged to engage with one or more tracks to induce vibration of the inner sleeve during movement of the needle sleeve between an extended position and a retracted position, wherein the one or more tracks are in the form of a zigzag or oscillating track on the surface of the inner sleeve, thereby causing the inner sleeve to vibrate during movement between the first configuration and the second configuration.

2. The injection device according to claim 1, wherein: 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 elongated housing; and In the second configuration, the needle sleeve is in a retracted position, in which the needle sleeve is received further within the elongated housing than in the extended position.

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

4. The injection device according to claim 1 or 2, wherein the outer sleeve extends beyond the inner sleeve in the distal direction.

5. The injection device according to claim 1 or 2, wherein the one or more tracks extend helically around the inner sleeve, and wherein the inner sleeve is freely rotatable relative to the elongated housing.

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

7. The injection device according to claim 1 or 2, wherein the portion of the needle sleeve configured for vibration and / or rotation comprises: One or more brushes extending in the distal direction; One or more protrusions and / or ridges extending in the distal direction; And / or one or more piezoelectric devices.

8. The injection device according to claim 1 or 2, wherein the injection device further comprises: A piston rod, which is capable of moving longitudinally within the elongated housing; and A piston spring configured to bias the piston rod toward the distal end of the elongated housing to engage the medication container when received within the elongated housing. The needle sleeve is configured to suppress vibration and / or rotation of the portion during longitudinal movement of the piston rod in the distal direction.

9. The injection device according to claim 1 or 2, wherein the injection device further comprises: A piston rod, which is capable of moving longitudinally within the elongated housing; and A piston spring configured to bias the piston rod toward the distal end of the elongated housing to engage the medication container when received within the elongated housing. The portion of the needle sleeve configured for vibration and / or rotation is further configured to vibrate and / or rotate during the longitudinal movement of the piston rod in the distal direction.

10. The injection device according to claim 1 or 2, wherein the needle sleeve is fixed relative to the elongated housing, and wherein: In the first configuration, the needle housing is in a retracted position, in which the needle held within the needle housing is shielded by the needle sleeve; and In the second configuration, the needle housing is in an extended position, in which the needle in the needle housing extends beyond the needle sleeve in the distal direction.

11. The injection device according to claim 1 or 2, further comprising a needle for dispensing a drug from the injection device, the needle being held in a position at the distal end of the elongated housing, the position being substantially fixed relative to the elongated housing such that the needle is shielded when the needle sleeve is in the extended position and exposed when the needle sleeve is in the retracted position.

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