Injection device having a brake device

Abstract

The injection device includes: an outer housing for receiving a medication container; and a drive mechanism for dispensing a medication from a medication container received in the outer housing. The drive mechanism includes a plunger rod and a displacement member configured to displace a distal end of the plunger rod into the medication container to dispense the medication. The device further includes a brake configured to receive a force from the displacement member to slow the displacement rate of the plunger rod.

Description

[Technical field]

[0001] The present invention relates to a drug injection device. [Background technology]

[0002] Injection devices, such as auto-injectors, typically include a sealed container of medication and a needle for injecting the medication into a patient. During an injection, a drive mechanism displaces a plunger into the medication container to dispense the medication from the needle. A coil spring typically provides the power to displace the plunger. As the coil spring expands, the force it exerts on the plunger decays according to Hooke's Law. Initially, the spring force is large and displaces the medication at a high rate. Some patients may find this high rate of medication delivery uncomfortable. Summary of the Invention [Means for solving the problem]

[0003] According to the present invention there is provided an injection device comprising: an outer housing for receiving the medication container; a drive mechanism for dispensing a medicament from a medicament container received in an outer housing, the drive mechanism including a plunger rod and a displacement member configured to displace a distal end of the plunger rod into the medicament container to dispense the medicament; Here, an injection device is provided, further comprising a brake configured to receive a force of the displacement member and control a displacement speed of the plunger rod.

[0004] The displacement member may include a spring.

[0005] Thus, the rate of drug delivery can be slowed down for patients who find a relatively high rate of drug delivery uncomfortable, especially at the beginning of the injection where the spring force is high.

[0006] The brake may include a braking surface in contact with an outer surface of the plunger rod such that movement of the plunger rod is resisted by friction between the braking surface and the outer surface of the plunger rod.

[0007] A region of the outer surface of the plunger is covered with a high friction material, said region being positioned to contact a braking surface of the brake during movement of the plunger between the initial position and the end stop positions.

[0008] The percentage of the outer surface of the plunger that is covered by the high friction material may increase towards the distal end of the plunger.

[0009] The coefficient of friction of the high friction material may change from a relatively low coefficient of friction to a relatively high coefficient of friction toward the distal end of the plunger.

[0010] Thus, the frictional force between the outer surface of the plunger and the braking surface decreases as the plunger is displaced, compensating for the decay of the spring force and providing a substantially constant injection rate.

[0011] An area of ​​the outer surface of the plunger includes a channel, said area being positioned to contact a braking surface of the brake during movement of the plunger between the initial position and the end stop position.

[0012] The width and / or depth of the channel decreases towards the distal end of the plunger.

[0013] Thus, the contact pressure between the brake and the plunger decreases as the plunger is displaced, compensating for the decay of the spring force.

[0014] The device may further include a braking force adjustment mechanism configured to adjust the contact pressure between the braking surface and the outer surface of the plunger rod.

[0015] Thus, the user can pre-set the injection rate according to patient preference.

[0016] The braking force adjustment mechanism may include a collar rotatably mounted to the housing, the collar being rotatable about a longitudinal axis of the device to adjust the contact pressure between the braking surface and the outer surface of the plunger rod.

[0017] Thus, the injection rate is easily adjusted.

[0018] The inner surface of the collar may contact the outer surface of the brake.

[0019] Therefore, the braking force adjustment mechanism can be easily constructed.

[0020] The outer surface of the brake may include a gradient such that the thickness of the brake increases circumferentially around the device, such that as the collar rotates, the contact pressure between the brake surface and the outer surface of the plunger rod varies depending on the direction of rotation of the collar.

[0021] The inner surface of the collar can include a gradient such that the thickness of the inner portion of the collar increases circumferentially around the device, such that as the collar rotates, the contact pressure between the brake surface and the outer surface of the plunger rod varies depending on the direction of rotation of the collar.

[0022] The braking force adjustment mechanism can include a sleeve slidably mounted to the housing, the sleeve configured to slide along a longitudinal axis of the device to adjust the contact pressure between the braking surface and the outer surface of the plunger rod.

[0023] Thus, an alternative braking force adjustment mechanism is provided which also provides easy adjustment of the injection rate.

[0024] The inner surface of the sleeve may contact the outer surface of the brake.

[0025] The outer surface of the brake can include a gradient such that the thickness of the brake increases in the longitudinal direction of the device, such that the contact pressure between the brake surface and the outer surface of the plunger rod varies depending on the direction the sleeve slides along the longitudinal axis.

[0026] The inner surface of the sleeve can include a gradient such that the thickness of the inner portion of the sleeve increases in the longitudinal direction of the device, such that the contact pressure between the braking surface and the outer surface of the plunger rod varies depending on the direction in which the sleeve slides along the longitudinal axis.

[0027] The plunger rod is tapered such that the diameter at the distal end of the plunger rod is greater than the diameter at the proximal end of the plunger rod.

[0028] Thus, the frictional force between the outer surface of the plunger and the braking surface decreases as the plunger is displaced, compensating for the decay of the spring force and providing a substantially constant injection rate.

[0029] The present invention also provides a method of operating an injection device, the method comprising: displacing a plunger rod of the injection device in a distal direction; and applying a braking force to the plunger rod to slow the rate of displacement of the plunger rod.

[0030] The method may further include operating a brake force adjustment mechanism of the injection device to adjust the predetermined displacement speed of the plunger rod.

[0031] The method may further comprise operating a brake force adjustment mechanism of the injection device to adjust the predetermined displacement speed of the plunger rod in response to information about the viscosity of the medicament of the injection device.

[0032] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0033] [Figure 1A] 1 is a schematic side view of an injection device embodying the present invention and a removable cap. [Figure 1B] FIG. 1B is a schematic side view of the injection device of FIG. 1A with the cap removed from the housing. [Diagram 2] FIG. 2 is a cross-sectional view of one embodiment of a device. [Diagram 3] FIG. 2 illustrates a plunger according to an embodiment of the present invention. [Figure 4] FIG. 2 is a cross-sectional view of one embodiment of a device. [Diagram 5] 2 is a cross-sectional view of a braking force adjustment mechanism according to an embodiment of the present invention. FIG. [Figure 6] FIG. 2 is a cross-sectional view of one embodiment of a device. [Figure 7] FIG. 4 is a detailed view of the braking force adjustment mechanism according to the embodiment of the present invention. [Figure 8] FIG. 2 illustrates a plunger according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0034] The drug delivery devices described herein are configured to inject a drug into a patient. For example, delivery can be subcutaneous, intramuscular, or intravenous. Such devices can be operated by the patient or a caregiver, such as a nurse or doctor, and can include various types of safety syringes, pen injectors, or auto-injectors. The devices can include cartridge-based systems that require piercing a sealed ampoule before use. The amount of drug delivered with these various devices can be about 0.5 mL to about 3 mL. Another device can include a large 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" amount of drug (usually about 2 mL to about 50 mL). Yet another device can include a pre-filled syringe within the housing of the device. The syringe can be fixed within the housing or movable within the housing, for example, movable from a retracted position to an actuated extended position.

[0035] In combination with a particular drug, the devices described herein are also customized to operate within required specifications. For example, the device is customized to inject the drug within a certain period of time (e.g., about 3 seconds to about 20 seconds for an auto-injector). Other specifications may include shelf life, expiration date, biocompatibility, environmental considerations, etc., for low or minimal levels of discomfort, or some conditions related to human factors. Such differences may arise due to a variety of factors, such as, for example, drugs with viscosities ranging 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.

[0036] The delivery device described herein may also include one or more automated features. For example, one or more of the following are automated: bringing together the needle and cartridge, needle insertion, drug injection, and needle retraction. Energy for one or more automated steps is provided by one or more energy sources. The energy sources may include, for example, mechanical energy, pneumatic energy, chemical energy, or electrical energy. For example, the mechanical energy source may include a spring, lever, elastomer, or other mechanical mechanism for storing or releasing energy. One or more energy sources may be integrated into a single device. The device may further include gears, valves, or other mechanisms for converting energy into the movement of one or more components of the device.

[0037] The one or more automated features of the auto-injector are each activated via an activation mechanism. Such an activation mechanism may include an actuator, such as one or more buttons, levers, needle sleeves, or other activation mechanisms. Activation of an automated feature may be a one-step or multi-step process. That is, the user may be required to activate one or more activation components to cause the automated feature to occur. For example, a one-step process may require the user to depress the needle sleeve against the user's body to inject medication. Other devices may require multi-step activation of an automated feature. For example, the user may be required to depress a button and retract a needle shield to cause an injection to occur.

[0038] In addition, 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 bringing the needle and cartridge together, 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 by a sequence of discrete steps.

[0039] Some delivery devices may include one or more features of a safety syringe, a pen injector, or an auto-injector. For example, one delivery device may include a mechanical energy source configured to automatically inject a medication (commonly found in auto-injectors) and a dose setting mechanism (commonly found in pen injectors).

[0040] An exemplary drug delivery device 10 according to some embodiments of the present disclosure is shown in Figures 1A and 1B. As described above, the device 10 is configured to inject a medication into a patient's body. The device 10 includes a housing 11 that includes a medication container 18 that defines a reservoir containing the medication to be injected, and components necessary to facilitate one or more stages of the delivery process. The medication container 18 can be a cartridge or a pre-filled syringe.

[0041] Device 10 may also include a cap 12 that is removably attachable to housing 11. Typically, a user must remove cap 12 from housing 11 before device 10 is operated.

[0042] As shown, the housing 11 is substantially cylindrical and has a substantially constant diameter along the 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.

[0043] The device 10 may also include a needle sleeve 19 coupled to the housing 11 such that the sleeve 19 can move 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 a proximal direction can allow the needle 17 to extend from a distal region D of the housing 11.

[0044] Insertion of needle 17 can occur via a number of mechanisms. For example, needle 17 is fixedly mounted relative to housing 11 and is initially in an extended needle sleeve 19. The distal end of sleeve 19 is placed against the patient's body and housing 11 is moved distally, thereby moving sleeve 19 proximally to uncover the distal end of needle 17. This relative movement allows the distal end of needle 17 to extend into the patient's body. Such insertion is referred to as "manual" insertion, since needle 17 is manually inserted by the patient's manual movement of housing 11 relative to sleeve 19.

[0045] Another form of insertion is "automated," whereby needle 17 moves relative to housing 11. Such insertion may be actuated by movement of sleeve 19 or by another form of actuation, such as, for example, button 13. As shown in FIGS. 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.

[0046] Other manual or automated functions may include drug injection or needle retraction, or both. Injection refers to the process of moving the bung or piston 14 from a proximal position to a more distal position within the cartridge 18 to force the medicament from the cartridge 18 through the needle 17. In some embodiments, a drive mechanism 20 is activated to expel the medicament from the cartridge 18. The drive mechanism 20 includes a drive spring 21. The drive spring 21 is compressed before the drive mechanism 20 is activated. A proximal end of the drive spring 21 is fixed within the proximal region P of the housing 11, and a distal end of the drive spring 21 is configured to apply a compressive force to a proximal face of the piston 14. Following activation, at least a portion of the energy stored in the drive spring 21 is applied to the proximal face of the piston 14. This compressive force acts on the piston 14 to move it in a distal direction. Such distal movement acts to compress the liquid medicament within the cartridge 18, expelling the liquid medicament from the needle 17.

[0047] Following injection, needle 17 can be retracted into sleeve 19 or housing 11. Retraction can occur when sleeve 19 moves distally as the user moves device 10 away from the patient's body. Retraction can occur when needle 17 remains in a fixed position relative to housing 11. Sleeve 19 is locked when the distal end of sleeve 19 passes the distal end of needle 17, sheathing needle 17. Such locking can include locking proximal movement of sleeve 19 relative to housing 11.

[0048] Another form of needle retraction may occur when the needle 17 moves relative to the housing 11. Such movement may occur when the cartridge 18 within the housing 11 moves proximally relative to the housing 11. This proximal movement is accomplished using a retraction spring (not shown) in the distal region D. The compressed retraction spring, when activated, can provide sufficient force to the cartridge 18 to move the syringe proximally. After sufficient retraction, a locking mechanism locks the relative movement between the needle 17 and the housing 11. Additionally, the button 13 or other components of the device 10 may be locked as desired.

[0049] FIG. 2 shows an injection device 10 according to one embodiment of the present invention.

[0050] The injection device 10 includes an elongated outer housing 201 having a proximal region P and a distal region D. The distal region D is relatively closer to the injection site and the proximal region P is relatively further from the injection site. In this embodiment, the housing 201 has a curved outer surface for easier handling. Preferably, the housing 201 is cylindrical.

[0051] The drug container 202 is supported within the outer housing 201 such that the drug container 202 is held in a fixed relationship relative to the housing 201. The proximal end of the drug container 202 is sealed by a piston 203 which, in use, is displaced within the drug container 202 to dispense the drug from the drug container 202. A needle 204 is provided in fluid communication with the distal end of the drug container 202. The needle 204 extends past the distal end of the housing 201 such that when the distal end of the housing 201 is pressed against an injection site, the needle 204 penetrates the injection site and the drug is delivered subcutaneously.

[0052] The drive mechanism 205 is provided in the proximal region P of the housing 201. The drive mechanism 205 is configured to displace the piston 203 into the drug container 202 in use. The drive mechanism 205 includes a displacement member 206 (hereinafter drive spring 206), a plunger 207, and a release mechanism 208. Before use, the plunger 207 is held in an initial position against the force of the spring 206 by the release mechanism 208.

[0053] A dose delivery button 209 is provided at the proximal end of the housing 201 and is mechanically coupled to a release mechanism 208. In use, the dose delivery button 209 is operated by a user causing the release mechanism 208 to release the plunger 207. The spring 206 then pushes the plunger 207 distally of the device 10. The distal end of the plunger 207 abuts the piston 203, which displaces together with the plunger 207 to dispense medicament from the medicament container 202.

[0054] The plunger 207 includes an elongated tube 210 with a closed distal end 211. The spring 206 is a coil spring and is disposed within the plunger 207. The distal end of the spring 206 abuts the closed end 211 of the plunger 207 and the proximal end of the spring 206 abuts an inner surface of the device 10. In the illustrated embodiment, this inner surface is the inner surface 212 of the dose delivery button 209.

[0055] The release mechanism 208 includes arms 213 extending from an inner surface 212 of the dose delivery button 209. A catch 214 is provided at the distal end of each arm 213. The catch 214 is configured to cooperate with a respective aperture 215 in the tubular wall 210 of the plunger 207 to hold the plunger 207 against the force of the spring 206. The catch 214 is released from the aperture 215 by manipulating the dose delivery button 209. For example, the dose delivery button 209 rotates the arm 213 in a circular motion about the longitudinal axis AA of the device 10. In this manner, the catch 214 is released from the aperture 215 and the plunger 207 is free to be displaced under the force of the spring 206.

[0056] The spring support 216 extends from the inner surface 212 of the dose delivery button 209 through the center of the spring 206. The spring support 216 is configured to support the spring 206 as the plunger 207 is displaced. When the plunger 207 is in an initial position, the spring 206 is disposed almost entirely within the plunger 207. However, during displacement of the plunger 207, the spring 206 extends from the proximal end of the plunger 207 and out of the support area of ​​the plunger tubular wall 210. The spring support 216 ensures that the spring 206 remains axially aligned with the device as it extends.

[0057] A needle sleeve 217 is provided at the distal end of the housing 201. The needle sleeve 217 extends from the distal end of the housing 201 to hide the needle 204 when the needle sleeve 217 is in an initial position. The needle sleeve 217 is telescopically displaceable into the housing 201 to expose the needle 204. The needle sleeve 217 is biased towards the initial position by a sleeve spring 218. Thus, the user presses the distal end of the device 10 against the injection site to displace the needle sleeve 217 into the housing 201 and cause the needle 204 to penetrate the injection site.

[0058] A cap 219 and needle shield 220 are provided for added security. The cap 219 fits over the needle sleeve 217 and must be removed along with the needle shield 220 prior to use.

[0059] During plunger 207 displacement, the force that spring 206 exerts on plunger 207 decays linearly as spring 206 expands, as will be apparent to those skilled in the art and derived from Hooke's Law. It should be understood that this effect is not limited to mechanical coil springs, but extends to other types of displacement members 206, such as compressed gas actuators and other types of pneumatic or mechanical springs. The illustrated embodiment includes a coil spring 206 by way of example only.

[0060] As the force decreases due to the spring expanding, the rate at which the drug is dispensed from the drug container 202 changes correspondingly: as the spring force decays, the rate at which the drug is dispensed also decays.

[0061] Additionally, the speed of injection may vary depending on the viscosity of the drug being injected. Drugs range in viscosity from about 3 cP to about 50 cP, which range has a corresponding effect on the rate at which the drug is dispensed for a given spring force. Temperature may also affect the viscosity of the drug, and therefore the rate at which the drug is dispensed.

[0062] The present invention aims to give the user of the device 10 more control over the rate at which medication is administered, as well as to compensate for changes in spring force damping and / or medication viscosity.

[0063] It has been found that different patients experience pain during injections differently, with some patients perceiving a faster injection as less painful, whereas others perceive a slower injection as less painful. As the delivery rate is not constant due to the decay of the spring force, some discomfort is likely to occur at some stage during the injection for the majority of patients.

[0064] Therefore, the present invention provides a brake 221 to slow the rate of advancement of the plunger 207 as the spring 206 displaces the plunger 207. The brake 221 comprises a material that is held against the plunger 207 so that the plunger is slowed down by friction.

[0065] 2, the brake 221 includes a cylindrical body 2211 with an inner surface 2212 in contact with an outer surface 222 of the cylindrical wall 210 of the plunger 207. The body 2211 is attached to the inner surface of the housing 201, or as shown, the body 2211 can abut the proximal end of the drug container 202, such that the body 2211 is held in a fixed relationship relative to the housing 201 during displacement of the plunger 207. Thus, as the plunger 207 is displaced, the outer surface 222 of the plunger 207 slides across the inner surface 2212 of the body 2211, so that movement of the plunger 207 is resisted by friction between the two surfaces 222, 2212.

[0066] 3 (plunger 207 shown separately), a region 223 of the outer surface 222 of plunger 207 is covered with a high friction material that provides greater friction with brake 221 than the remainder of the outer surface of plunger 207.

[0067] The proportion of the outer surface 222 covered by the region of high friction material increases towards the distal end D of the plunger 207. For example, in the illustrated embodiment, the opposing edges 224 of the region of high friction material 223 extending longitudinally along the length of the plunger 207 are sloped such that the width of said region 223 increases towards the distal end D of the plunger 207. Thus, friction between the brake 221 and the plunger 207 decreases as the plunger 207 is displaced. This compensates for the damping of the spring force, so that when the plunger 207 is displaced by the spring 206, the region of high friction material 223 causes the plunger 207 to move at a constant speed over the entire range it moves between the initial position and the end stop position.

[0068] In another embodiment shown in FIG. 4, where similar features retain the same reference numbers, the device further includes a brake force adjustment mechanism 401. The brake force adjustment mechanism 401 is configured to allow the user to change the speed at which the plunger 207 is displaced (hereinafter referred to as the injection speed). The brake force adjustment mechanism 401 is operable to adjust the force between the brake 221 and the plunger 207 (hereinafter referred to as the brake force). Thus, if the patient prefers a slower injection, the brake force adjustment mechanism 401 can be used to reduce the injection speed and vice versa. Thus, the brake force adjustment mechanism 401 allows the user to control the injection speed according to his / her preference. The brake force adjustment mechanism 401 can also be used to compensate for the individual viscosity of the medicament to be injected. For example, a medicament having a first viscosity is injected at a first injection speed, and a medicament having a second viscosity higher than the first viscosity is injected at a second injection speed, where the second injection speed is slower than the first injection speed. Thus, if the device comprises a drug with a relatively low viscosity, the user can adjust the braking force adjustment mechanism 401 to increase the braking force to maintain the injection rate as close as possible to the user's preferred injection rate. Similarly, if the device comprises a drug with a relatively high viscosity, the user can adjust the braking force adjustment mechanism 401 to decrease the braking force to maintain the injection rate as close as possible to the user's preferred injection rate. In one embodiment, the user is provided with information regarding the viscosity of the drug and the corresponding setting of the braking force adjustment mechanism 401 to allow the user to select from a range of predetermined injection rates.

[0069] 4, the braking force adjustment mechanism 401 includes a collar 4011 supported in a proximal region of the housing 201 that overlaps the plunger 207. The collar 4011 is rotatably supported such that a user can rotate the collar 4011 about the longitudinal axis AA of the device 10. Rotating the collar 4011 in one direction increases the injection rate and rotating it in the other direction decreases the injection rate, as described further below.

[0070] The collar 4011 includes an outer surface 4012 that a user can grasp to rotate the collar 4011 about the longitudinal axis AA of the device 10; and an inner surface 4013 that is configured to interact with the brake 221. When the collar 4011 is rotated in one direction, the brake 221 is pressed against the plunger 207 with a greater force.

[0071] Collar 4011 rotates between a first position (which provides the fastest injection rate) and a second position (which provides the slowest injection rate).

[0072] In the first position, the brake 221 presses against the plunger 207 with the least force. In the second position, the brake 221 presses against the plunger 207 with the most force. Rotation of the collar 4011 between the first and second positions changes the force with which the brake 221 presses against the plunger 207. Rotation of the collar 4011 towards the second position increases the force with which the brake 221 presses against the plunger 207. Thus, by rotating the collar 4011, the injection speed can be fine-tuned to suit the patient's preference.

[0073] In this embodiment, the brake 221 is integrally formed with the housing 201 and includes at least one arm 2213 extending from an inner surface of the housing 201. Although two arms 2213 are shown in Figure 4, it will be understood that the brake 221 may include multiple arms 2213 spaced about the inner surface of the housing 201.

[0074] The arm 2213 includes a hinge 2214 and a brake shoe 2215. The hinge 2214 cantilevers from an inner surface of the housing 201 toward the plunger 207. The brake shoes 2215 extend longitudinally of the device 10 from either end of the hinge 2214. The brake shoes 2215 provide a braking surface 2216 configured to contact the outer surface 222 of the plunger 207.

[0075] Opposite the braking surface 2216, the outer surface 2217 of the brake shoe 2215 contacts the inner surface 4013 of the collar 4011. The outer surface 2217 of the brake shoe 2215 is provided with a slope such that the thickness of the brake shoe 2215 increases in the circumferential direction of the device 10. Thus, when the collar 4011 is rotated, the contact pressure between the inner surface 4013 of the collar and the outer surface 2217 of the brake shoe 2215 varies depending on the direction of rotation of the collar 4011. When the collar 4011 is rotated in a direction in which the thickness of the brake shoe 2215 increases, the contact pressure between the inner surface 4013 of the collar and the outer surface 2217 of the brake shoe 2215 increases. Similarly, when the collar 4011 is rotated in the opposite direction, said contact pressure decreases.

[0076] Increasing the contact pressure between the inner surface 4013 of the collar and the outer surface 2217 of the brake shoe 2215 increases the force with which the brake 221 is pressed against the plunger 207 .

[0077] The inner and outer surfaces 4013, 4012 of the collar 4011 are connected to one another by at least one connecting portion 4014. The connecting portion 4014 extends through a slot 225 in the housing 201. The slot 225 extends circumferentially to allow the collar 4011 to rotate.

[0078] Figure 5 shows a cross section of the brake force adjustment mechanism 401 of Figure 4 transverse to the longitudinal axis of the device. In the embodiment shown in Figure 5, the inner surface 4013 of the collar includes four bumps 4015 (in this case hemispherical protrusions on the inner surface 4013), each of which contacts the outer surface 2217 of a respective brake shoe 2215. These bumps 4015 and brake shoes 2215 are spaced 90 degrees apart to evenly distribute the pressure applied to the outer surface 222 of the plunger 207. The connecting portions 4014 are also spaced 90 degrees apart and sit in corresponding slots in the housing (not shown).

[0079] In an alternative configuration of the embodiment of FIG. 4, the bumps 4015 on the inner surface 4013 of the collar 4011 are omitted and the inner surface 4013 is smooth. In this configuration, the inner surface 4013 is provided with a gradient such that the thickness of the inner portion 4016 of the collar 4011 increases in the circumferential direction of the device 10. Thus, when the collar 4011 is rotated, the contact pressure between the inner surface 4013 of the collar and the outer surface 2217 of the brake shoe 2215 changes depending on the direction of rotation of the collar 4011. When the collar 4011 is rotated in a direction that increases the thickness of the inner portion 4016 of the collar 4011, the contact pressure between the inner surface 4013 of the collar and the outer surface 2217 of the brake shoe 2215 increases. Similarly, when the collar 4011 is rotated in the opposite direction, the contact pressure decreases. In such a configuration, the thickness of the shoe 2215 may be constant in the circumferential direction.

[0080] 6, the braking force adjustment mechanism 401 includes a sleeve supported at a proximal region of the housing 201 that overlaps the plunger 207. The sleeve 4017 is slidably supported such that a user can slide the sleeve 4017 along the longitudinal axis AA of the device 10. Sliding the sleeve 4017 in one direction increases the injection rate and sliding it in the other direction decreases the injection rate, as described further below.

[0081] The sleeve 4017 includes an outer surface 4018 that a user can grip to slide the sleeve 4017 about the longitudinal axis AA of the device 10; and an inner surface 4019 that is configured to interact with the brake 221. When the sleeve 4017 is slid in one direction, the brake 221 is pressed against the plunger 207 with a greater force.

[0082] The sleeve 4017 is slidable between a first position (which provides the fastest injection rate) and a second position (which provides the slowest injection rate).

[0083] In the first position, the brake 221 presses against the plunger 207 with the least force. In the second position, the brake 221 presses against the plunger 207 with the most force. Sliding the sleeve 4017 between the first and second positions changes the force with which the brake 221 presses against the plunger 207. As the sleeve 4017 slides towards the second position, the force with which the brake 221 presses against the plunger 207 increases. Thus, by sliding the sleeve 4017, the injection speed can be fine-tuned to suit the patient's preference.

[0084] 4 and 5 embodiment, the brake 221 includes at least one arm 2213 extending from an inner surface of the housing 201. Although two arms 2213 are shown in FIG. 6, it will be appreciated that the brake 221 may include multiple arms 2213 spaced about the inner surface of the housing 201.

[0085] The arm 2213 includes a hinge 2214 and a brake shoe 2215. The hinge 2214 extends from an inner surface of the housing 201 toward the plunger 207. The brake shoes 2215 extend from either end of the hinge 2214 in the longitudinal direction of the device 10. The brake shoes 2215 provide a braking surface 2216 configured to contact the outer surface 222 of the plunger 207.

[0086] Opposite the braking surface 2216, the outer surface 2217 of the brake shoe contacts the inner surface 4019 of the sleeve 4017. The inner surface 4019 of the sleeve 4017 is provided with a gradient such that the thickness of the inner part 4020 of the sleeve 4017 increases in the circumferential direction of the device. Thus, the contact pressure between the inner surface 4019 of the sleeve and the outer surface 2217 of the brake shoe 2215 varies depending on the direction in which the sleeve 4017 is slid. If the user slides the sleeve 4017 in a direction in which the thickness of the inner part 4020 of the sleeve 4017 increases, the contact pressure between the inner surface 4019 of the sleeve and the outer surface 2217 of the brake shoe 2215 increases. Similarly, if the user slides the sleeve 4017 in the opposite direction, said contact pressure decreases.

[0087] Increasing the contact pressure between the inner surface 4019 of the sleeve and the outer surface 2217 of the brake shoe 2215 increases the force with which the brake 221 is pressed against the plunger 207 .

[0088] The inner portion 4020 of the sleeve is connected to the outer portion 4021 of the sleeve 4017 by at least one connecting portion 4022. The connecting portion 4022 extends through a slot in the housing 201. The slot extends longitudinally of the device 10 to allow the sleeve 4017 to slide as described.

[0089] FIG. 7 shows a detailed view of an alternative configuration of the embodiment of FIG. 6, where the outer surface 2217 of the brake shoe 2215 is provided with a gradient such that the thickness of the brake shoe 2215 increases in the longitudinal direction of the device 10. In this embodiment, the inner surface 4019 of the sleeve 4017 includes bumps 4023 that contact the outer surface 2217 of the brake shoe 2215. Thus, the contact pressure between the inner surface 4019 of the sleeve and the outer surface 2217 of the brake shoe 2215 varies depending on the direction in which the sleeve 4017 is slid. When the user slides the sleeve 4017 in a direction in which the thickness of the brake shoe 2215 increases, the contact pressure between the inner surface 4019 of the sleeve and the outer surface 2217 of the brake shoe 2215 increases. Similarly, when the user slides the sleeve 4017 in the opposite direction, said contact pressure decreases.

[0090] In the above embodiment, the region of high friction material 223 may include a plurality of separate regions of high friction material spaced about the outer surface 222 of the plunger 207 such that each separate region of high friction material contacts the braking surface 2216 of a respective brake shoe 2215. For example, the plurality of separate regions 223 includes four separate regions spaced at 90 degree intervals.

[0091] In the above embodiment, instead of the region 223 of high friction material, the plunger 207 comprises at least one channel 226 in its outer surface 222, as shown in FIG. 8. The at least one channel 226 is configured to reduce the contact area between the outer surface 222 of the plunger 207 and the braking surface 2216 of the respective brake shoe 2215 that overlaps the channel 226. The width of the channel 226 increases towards the proximal end P of the plunger 207. Thus, the percentage of the braking surface 2216 of the brake shoe 2215 that overlaps the channel 226 increases as the plunger 207 is displaced towards the end stop, and the contact area between the outer surface 222 of the plunger 207 and the braking surface 2216 decreases. Furthermore, changing the width of the channel 226 effectively changes the deflection of the brake 221. These effects combine to correspondingly reduce the friction between the braking surface 2216 and the plunger 207, thereby compensating for the damping of the spring force. In this manner, the channel is configured to move at a constant velocity throughout the range of movement of the plunger 207 between the initial position and the end stop position. It should be appreciated that as well as / instead of varying the width of the channel 226, it is also possible to reduce friction between the braking surface 2216 and the plunger 207 by increasing the depth of the channel 226 toward the proximal end P of the plunger 207. In particular, by increasing the depth of the channel 226, the contact pressure between the braking surface 2216 and the plunger is reduced. In such an embodiment, at least a portion of the braking surface is within the channel 226.

[0092] In the above embodiment, the at least one channel 226 may include a plurality of separate channels spaced apart about the outer surface 222 of the plunger 207 such that each separate channel is disposed beneath the braking surface 2216 of a respective brake shoe 2215. For example, the plurality of separate channels includes four separate channels spaced apart at 90 degree intervals.

[0093] In the above embodiment, the plunger 207 is tapered such that the outer diameter of the plunger 207 at the distal end of the plunger 207 is slightly larger than the outer diameter of the plunger 207 at the proximal end of the plunger 207. Thus, during displacement of the plunger 207, the contact force between the brake 221 and the plunger 207 decreases as the plunger is displaced towards the end stop position.

[0094] The injection device embodiments described herein are configured to receive a drug cartridge or a pre-filled syringe, where the term "drug container" is intended to encompass both drug cartridges and pre-filled syringes.

[0095] 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.

[0096] 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.

[0097] 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.

[0098] 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.

[0099] 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).

[0100] 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.

[0101] 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.

[0102] An exemplary oligonucleotide is, for example, the cholesterol-lowering antisense therapeutic mipomersen / quinamro for the treatment of familial hypercholesterolemia.

[0103] Exemplary DPP4 inhibitors are vidagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

[0104] 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.

[0105] 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.

[0106] 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.

[0107] 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.

[0108] 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.

[0109] 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).

[0110] 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.

[0111] 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.

[0112] Pharmaceutically acceptable solvates are, for example, hydrates or alkanolates, such as methanolates or ethanolates.

[0113] 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 includes such modifications, and any and all equivalents thereof.

Claims

1. 1. An injection device comprising: an outer housing for receiving the medication container; a drive mechanism for dispensing a medicament from a medicament container received in the outer housing, the drive mechanism including a plunger rod and a displacement member configured to displace a distal end of the plunger rod into the medicament container to dispense the medicament; wherein the brake is configured to receive a force of the displacement member to control a displacement rate of the plunger rod, the brake including a brake surface contacting an outer surface of the plunger rod such that movement of the plunger rod is resisted by friction between the brake surface and the outer surface of the plunger rod; further including a brake force adjustment mechanism configured to adjust the contact pressure between the braking surface and the outer surface of the plunger rod; the braking force adjustment mechanism includes a collar rotatably mounted on the housing, the collar being rotatable about a longitudinal axis of the device to adjust the contact pressure between the braking surface and the outer surface of the plunger rod; or The braking force adjustment mechanism includes a sleeve slidably mounted to the housing, the sleeve configured to slide along a longitudinal axis of the device to adjust the contact pressure between the braking surface and the outer surface of the plunger rod. The injection device.

2. 2. The injection device of claim 1, wherein an area of ​​an outer surface of the plunger is covered with a high friction material, said area being arranged to contact a braking surface of the brake during movement of the plunger between the initial position and the end stop position.

3. An injection device as described in claim 2, wherein the proportion of the outer surface of the plunger covered by the high friction material increases toward the distal end of the plunger.

4. 4. An injection device according to claim 2 or 3, wherein the coefficient of friction of the high-friction material changes from a relatively low coefficient of friction to a relatively high coefficient of friction towards the distal end of the plunger.

5. 2. The injection device of claim 1, wherein an area of ​​an outer surface of the plunger comprises a channel, said area being arranged to contact a braking surface of the brake during movement of the plunger between the initial position and the end stop position.

6. An injection device as described in claim 5, wherein the width and / or depth of the channel decreases towards the distal end of the plunger.

7. 2. The injection device of claim 1, wherein an inner surface of the collar contacts an outer surface of the brake.

8. an outer surface of the brake includes a gradient such that the thickness of the brake increases circumferentially around the device, so that as the collar rotates, the contact pressure between the brake surface and the outer surface of the plunger rod varies depending on the direction of rotation of the collar; or 8. The injection device according to claim 7, wherein the inner surface of the collar includes a gradient such that the thickness of the inner portion of the collar increases in a circumferential direction of the device, whereby, when the collar rotates, the contact pressure between the brake surface and the outer surface of the plunger rod varies depending on the direction of rotation of the collar.

9. 2. The injection device of claim 1, wherein an inner surface of the sleeve contacts an outer surface of the brake.

10. the outer surface of the brake includes a gradient such that the thickness of the brake increases in the longitudinal direction of the device, whereby the contact pressure between the brake surface and the outer surface of the plunger rod varies depending on the direction that the sleeve slides along the longitudinal axis; or 10. The injection device of claim 9, wherein the inner surface of the sleeve includes a gradient such that the thickness of the inner portion of the sleeve increases in the longitudinal direction of the device, whereby the contact pressure between the braking surface and the outer surface of the plunger rod varies depending on the direction in which the sleeve slides along the longitudinal axis.

11. An injection device according to any one of claims 1 to 10, wherein the plunger rod is tapered such that the diameter at the distal end of the plunger rod is greater than the diameter at the proximal end of the plunger rod.

12. An injection device according to any one of claims 1 to 11, wherein the device further comprises a reservoir of medicament.

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