Injector device with brake arrangement

Abstract

A syringe device comprises: an outer housing for accommodating a medicament container; and a drive mechanism for dispensing a medicament from the medicament container accommodated in the outer housing. The drive mechanism comprises a plunger rod and a displacement member, the displacement member being configured to displace a distal end of the plunger rod into the medicament container to dispense the medicament. The device further comprises a brake, the brake being configured to slow down the displacement rate of the plunger rod under the force of the displacement member.

Description

Technical Field

[0001] The present invention relates to an injector device for a medicament. Background Art

[0002] Injection devices (e.g., automatic syringes) typically have sealed medicament containers and needles for injecting medicament into patients. During injection, a drive mechanism displaces a plunger into the medicament container to dispense medicament through a needle. Typically, a coil spring provides the motive force for displacing the plunger. When the coil spring extends, the force applied by the spring on the plunger decays according to Hooke's law. Initially, the spring force is high and dispenses medicament at a high rate. For some patients, this high rate of medicament delivery may be uncomfortable. Summary of the invention

[0003] According to the present invention, there is provided a syringe device comprising:

[0004] an outer housing for housing a medicament container; and

[0005] a drive mechanism for dispensing a medicament from a medicament container accommodated in the outer housing; the drive mechanism comprising 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;

[0006] The device further comprises a brake configured to control a displacement rate of the plunger rod under the force of the displacement member.

[0007] The displacement member may comprise a spring.

[0008] Thus, for patients who find relatively high medicament delivery rates uncomfortable, the medicament delivery rate may be slowed, particularly at the beginning of an injection when the spring force is high.

[0009] The brake may include a braking surface that contacts 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.

[0010] An area of ​​the outer surface of the plunger may be covered with a high friction material, the area being arranged to contact the braking surface of the brake during movement of the plunger between an initial position and an end stop position.

[0011] The proportion of the outer surface of the plunger covered by the high friction material may increase toward the distal end of the plunger.

[0012] 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.

[0013] Thus, the friction between the outer surface of the plunger and the braking surface decreases as the plunger is displaced, thereby compensating for the decay of the spring force and resulting in a substantially constant injection rate.

[0014] A region of the outer surface of the plunger may be provided with a channel, the region being arranged to contact the braking surface of the brake during movement of the plunger between an initial position and an end stop position.

[0015] The width and / or depth of the channel may decrease towards the distal end of the plunger.

[0016] Therefore, the contact pressure between the brake and the plunger decreases as the plunger is displaced to compensate for the decay of the spring force.

[0017] 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.

[0018] Thus, the user can pre-set the injection rate according to the patient's preference.

[0019] The braking force adjustment mechanism may include a collar rotatably mounted on the housing, the collar being rotatable about the longitudinal axis of the device to adjust the contact pressure between the braking surface and the outer surface of the plunger rod.

[0020] Therefore, the injection speed is easily adjusted.

[0021] An inner surface of the lining may contact an outer surface of the brake.

[0022] Therefore, the braking force adjustment mechanism is easily constructed.

[0023] The outer surface of the brake may include a gradient such that the thickness of the brake increases in a circumferential direction of the device, so that when the liner is rotated, the contact pressure between the brake surface and the outer surface of the plunger rod varies depending on the rotation direction of the liner.

[0024] The inner surface of the liner may include a gradient such that the thickness of the inner portion of the liner increases in a circumferential direction of the device, so that when the liner is rotated, the contact pressure between the braking surface and the outer surface of the plunger rod varies depending on the rotation direction of the liner.

[0025] The braking force adjustment mechanism may include a sleeve slidably mounted to the housing, the sleeve being 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.

[0026] Thus, an alternative braking force adjustment mechanism is provided which provides an equally easy adjustment of the injection speed.

[0027] An inner surface of the sleeve may contact an outer surface of the brake.

[0028] The outer surface of the stopper may comprise a gradient such that the thickness of the stopper increases in a longitudinal direction of the device such that the contact pressure between the stopper surface and the outer surface of the plunger rod varies depending on the direction in which the sleeve slides along the longitudinal axis.

[0029] The inner surface of the sleeve may 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.

[0030] The plunger rod may be tapered such that the distal end of the plunger rod has a larger diameter than a proximal end of the plunger rod.

[0031] Thus, the friction between the outer surface of the plunger and the braking surface decreases as the plunger is displaced, thereby compensating for the decay of the spring force and resulting in a substantially constant injection rate.

[0032] Also according to the present invention, there is provided a method of operating a syringe device, the method comprising: displacing a plunger rod of the syringe device in a distal direction; and applying a braking force to the plunger rod to slow the displacement rate of the plunger rod.

[0033] The method may further include operating a braking force adjustment mechanism of the injector device to adjust a predetermined rate of displacement of the plunger rod.

[0034] The method may further comprise operating the braking force adjustment mechanism of the injector device to adjust a predetermined displacement rate of the plunger rod in response to information regarding the viscosity of a medicament of the injector device. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0036] FIG1A is a schematic side view of a syringe device and a removable cap embodying the present invention;

[0037] FIG. 1B is a schematic side view of the syringe device of FIG. 1A with the cap removed from the housing;

[0038] FIG2 shows a cross section of an embodiment of the device;

[0039] FIG3 shows a plunger according to an embodiment of the present invention;

[0040] FIG4 shows a cross section of an embodiment of the device;

[0041] FIG5 shows a cross section of a braking force adjustment mechanism according to an embodiment of the present invention;

[0042] FIG6 shows a cross section of an embodiment of the device;

[0043] 7 is a detailed view of a braking force adjustment mechanism according to an embodiment of the present invention; and

[0044] FIG. 8 shows a plunger according to an embodiment of the present invention. DETAILED DESCRIPTION

[0045] As described herein, the drug delivery device can be configured to inject the medicament into the patient. For example, the delivery can be subcutaneous, intramuscular or intravenous. This device can be operated by the patient or a caregiver (such as a nurse or a physician), and can include various types of safety syringes, pen-type syringes or automatic syringes. The device may include a cartridge-based system that requires piercing a sealed ampoule before use. The volume of the medicament delivered with these different devices can vary in the range of about 0.5ml to about 3ml. Another device may include a large volume device ("LVD") or a patch pump, which is configured to adhere to the patient's skin for a period of time (e.g., about 5, 15, 30, 60 or 120 minutes) to deliver a "large" volume of medicament (typically about 2ml to about 50ml). Yet another device may include a prefilled syringe in the housing of the device. The syringe may be fixed in the housing or may be able to move in the housing, such as from a retracted position to an operational extended position.

[0046] In conjunction with specific medicaments, the currently described device can also be customized to operate within the required specification. For example, the device can be customized to inject medicament in a certain time period (for example, about 3 seconds to about 20 seconds for automatic injector). Other specifications can include low-level or minimum-level discomfort, or certain conditions related to human factors, shelf life, validity period, biocompatibility, environmental factors, etc. This change may be caused by various factors, such as, the viscosity of the drug changes in the range of about 3cP to about 50cP. Therefore, the drug delivery device will usually include a hollow needle with a size range from about 25 to about 31 gauges. Common sizes are 17 and 29 gauges.

[0047] The delivery devices described herein may also include one or more automated functions. For example, one or more of the combination of the needle and the cartridge, the needle insertion, the injection of the medicament, and the needle retraction may be automated. The energy for one or more automated steps may be provided by one or more energy sources. The energy source may include, for example, mechanical energy, pneumatic energy, chemical energy, or electrical energy. For example, a mechanical energy source may include a spring, a lever, an 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.

[0048] The one or more automated functions of the automatic injector may each be activated via an activation mechanism. Such an activation mechanism may include an actuator, such as one or more of a button, a lever, a needle sleeve, or other activation components. Activation of the automated function may be a one-step process or a multi-step process. That is, the user may need to activate one or more activation components in order to produce the automated function. For example, in a one-step process, the user may press the needle sleeve against their body to cause the injection of the medicament. Other devices may require multi-step activation of the automated function. For example, the user may be required to press a button and retract the needle shield to cause the injection.

[0049] Additionally, activation of one automated function may activate one or more subsequent automated functions, thereby forming an activation sequence. For example, activation of a first automated function may activate at least two of needle and cartridge engagement, needle insertion, medicament 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.

[0050] Some delivery devices may include one or more functions of a safety syringe, a pen injector, or an auto-injector. For example, a delivery device may include a mechanical energy source configured to automatically inject a medicament (as typically found in an auto-injector) and a dose setting mechanism (as typically found in a pen injector).

[0051] According to some embodiments of the present disclosure, an exemplary drug delivery device 10 is shown in Figures 1A and 1B. As described above, the device 10 is configured to inject a medicament into a patient. The device 10 includes a housing 11, which contains a medicament container 18 defining a reservoir containing the medicament to be injected, and components required to facilitate one or more steps of the delivery process. The medicament container 18 can be a cartridge or a prefilled syringe.

[0052] The device 10 may also include a cap 12 that may be removably mounted to the housing 11. Typically, a user must remove the cap 12 from the housing 11 before the device 10 can be operated.

[0053] As shown, the housing 11 is generally 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 position relatively closer to the injection site, and the term "proximal" refers to a position relatively farther from the injection site.

[0054] The device 10 may further 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 move in a longitudinal direction parallel to the longitudinal axis AA. Specifically, movement of the sleeve 19 in a proximal direction may allow the needle 17 to extend from a distal region D of the housing 11.

[0055] Insertion of needle 17 can occur via several mechanisms. For example, needle 17 can be fixedly positioned relative to housing 11 and initially located within an extended needle sleeve 19. Proximally moving sleeve 19 by placing the distal end of sleeve 19 against the patient's body and moving housing 11 in a distal direction will expose the distal end of needle 17. This relative movement allows the distal end of needle 17 to extend into the patient's body. This insertion is referred to as a "manual" insertion because needle 17 is manually inserted via the patient manually moving housing 11 relative to sleeve 19.

[0056] Another form of insertion is "automatic", whereby the needle 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, the button 13 is located at the proximal end of the housing 11. However, in other embodiments, the button 13 can be located on one side of the housing 11.

[0057] Other manual or automated features may include drug injection or needle retraction or both. Injection is the process of the stopper or piston 14 moving from a proximal position to a more distal position in the reservoir of the cartridge 18 so as to force the medicament from the cartridge 18 through the needle 17. In some embodiments, the drive mechanism is activated to force the medicament to leave the cartridge 18. The drive mechanism includes a drive spring. Before the drive mechanism is activated, the drive spring is in a compressed state. The proximal end of the drive spring can be fixed in the proximal region P of the housing 11, and the distal end of the drive spring can be configured to apply a compressive force to the proximal surface of the piston 14. After activation, at least a portion of the energy stored in the drive spring can be applied to the proximal surface of the piston 14. The compressive force can act on the piston 14 to move it in the distal direction. This distal movement is used to compress the liquid medicament in the cartridge 18, thereby forcing it to leave from the needle 17.

[0058] After injection, the needle 17 can be retracted into the sleeve 19 or the housing 11. When the user removes the device 10 from the patient's body, the retraction can occur when the sleeve 19 moves distally. This can occur 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.

[0059] 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 in a proximal direction relative to the housing 11. This proximal movement can be achieved by using a retraction spring (not shown) located in the distal region D. The compressed retraction spring can provide sufficient force to the cartridge 18 to move it in a proximal direction when activated. After sufficient retraction, any relative movement between the needle 17 and the housing 11 can be locked with a locking mechanism. In addition, the button 13 or other components of the device 10 can be locked as desired.

[0060] FIG. 2 shows a syringe device 10 according to one embodiment of the present invention.

[0061] The syringe device 10 comprises 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 away from the injection site. In the present embodiment, the housing 201 has a curved outer surface for more comfortable operation. Preferably, the housing 201 is cylindrical.

[0062] The medicament container 202 is supported within the outer housing 201 so that the medicament container 202 is held in a fixed relationship relative to the housing 201. The proximal end of the medicament container 202 is sealed by a piston 203, which is displaced into the medicament container 202 in use to dispense medicament from the medicament container 202. The needle 204 is arranged to be in fluid communication with the distal end of the medicament container 202. The needle 204 extends beyond the distal end of the housing 201 so that when the distal end of the housing 201 is pressed against the injection site, the needle 204 pierces the injection site to deliver the medicament subcutaneously.

[0063] The drive mechanism 205 is disposed in the proximal region P of the housing 201. In use, the drive mechanism 205 is configured to displace the piston 203 into the medicament container 202. The drive mechanism 205 includes a displacement member 206 (hereinafter referred to as a drive spring 206), a plunger 207, and a release mechanism 208. Before use, the plunger 207 is held in an initial position by the release mechanism 208 overcoming the force of the spring 206.

[0064] The dose delivery button 209 is disposed in the proximal end of the housing 201 and is mechanically coupled to the release mechanism 208. During use, the dose delivery button 209 is manipulated by the user to cause the release mechanism 208 to release the plunger 207. The spring 206 then pushes the plunger 207 in the distal direction of the device 10. The distal end of the plunger 207 abuts the piston 203, so that the piston 203 is displaced together with the plunger 207 to dispense the medicament from the medicament container 202.

[0065] The plunger 207 comprises an elongated tube 210 having 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, while the proximal end of the spring 206 abuts an inner surface of the device 10. In the illustrated embodiment, the inner surface is an inner surface 212 of the dose delivery button 209.

[0066] 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 corresponding hole 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 can be removed from the hole 215 by manipulating the dose delivery button 209. For example, the dose delivery button 209 can be rotated to move the arm 213 in a circular manner around the longitudinal axis AA of the device 10. In this way, the catch 214 is removed from the hole 215, and the plunger 207 is then free to displace under the force of the spring 206.

[0067] The spring support 216 extends from the inner surface 212 of the dose delivery button 209 and passes through the center of the spring 206. The spring support 216 is configured to support the spring 206 when the plunger 207 is displaced. When the plunger 207 is in the initial position, the spring 206 is almost completely disposed within the plunger 207. However, during displacement of the plunger 207, the spring 206 extends from the proximal end of the plunger 207 and exceeds the support range of the tubular wall 210 of the plunger. The spring support 216 ensures that the spring 206 remains axially aligned with the device when it is deployed.

[0068] The needle sleeve 217 is disposed in the distal end of the housing 201. When the needle sleeve 217 is in the initial position, the needle sleeve 217 extends from the distal end of the housing 201 to shield the needle 204. The needle sleeve 217 can be displaced into the housing 201 in a telescopic manner to expose the needle 204. The needle sleeve 217 is biased into the initial position by the sleeve spring 218. Therefore, the user can press 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.

[0069] A cap 219 and a needle shield 220 are provided for additional safety. The cap 219 is located on the needle sleeve 217 and must be removed together with the needle shield 220 before use.

[0070] During displacement of the plunger 207, the force exerted by the spring 206 on the plunger 207 decays linearly as the spring 206 extends. This will be apparent to any skilled person and can be derived from Hooke's law. It should be understood that this effect is not limited to mechanical coil springs and 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.

[0071] The drop in force due to the extension of the spring results in a corresponding change in the rate at which medicament is dispensed from the medicament container 202: as the spring force decays, the rate at which medicament is dispensed also decays.

[0072] In addition, the injection rate can vary depending on the viscosity of the injected medicament. The viscosity of the medicament varies in the range of about 3 cP to about 50 cP, and this range will have a corresponding effect on the rate at which the medicament is dispensed at a given spring force. Temperature can also affect the viscosity of the medicament, and therefore the rate at which the medicament is dispensed.

[0073] The present invention is intended to provide the user of device 10 with more control over the rate at which medicament is dispensed and to compensate for spring force decay and / or changes in medicament viscosity.

[0074] It has been determined that during an injection, pain perception varies among patients. In some patients, a fast injection is perceived as less painful, while in other patients, a slow injection is perceived as less painful. Having inconsistent delivery rates due to decaying spring force is likely to cause some discomfort at some stage during the injection process for most patients.

[0075] Therefore, the present invention provides a brake 221 to slow the rate of travel of the plunger 207 as it is displaced by the spring 206. The brake 221 comprises a material that is held against the plunger 207 so that the plunger is slowed by friction.

[0076] 2 , the stopper 221 comprises a cylindrical body 2211 having an inner side surface 2212 in contact with an outer surface 222 of the tubular wall 210 of the plunger 207. The body 2211 may be attached to the inner surface of the housing 201, or, as shown, the body 2211 may abut the proximal end of the medicament container 202, such that the body 2211 remains in a fixed relationship relative to the housing 201 during displacement of the plunger 207. Thus, when the plunger 207 is displaced, the outer surface 222 of the plunger 207 slides over the inner side surface 2212 of the body 2211, such that movement of the plunger 207 is resisted by friction between the two surfaces 222, 2212.

[0077] 3 (where the plunger 207 is shown alone), an area 223 of the outer surface 222 of the plunger 207 is covered with a high friction material. The high friction material creates greater friction with the brake 221 than the rest of the outer surface of the plunger 207.

[0078] The proportion of the outer surface 222 covered by the high friction material area increases toward the distal end D of the plunger 207. For example, in the illustrated embodiment, the opposite edges 224 of the high friction material area 223 extending longitudinally along the length of the plunger 207 are inclined so that the width of the area 223 increases toward the distal end D of the plunger 207. Therefore, when the plunger 207 is displaced, the friction between the brake 221 and the plunger 207 decreases. This compensates for the decay of the spring force so that when the plunger 207 is displaced by the spring 206, the high friction material area 223 moves the plunger 207 at a constant speed through its full range of movement between the initial position and the end stop position.

[0079] In another embodiment shown in FIG. 4 , in which the same features retain the same reference numerals, the device further comprises a braking force adjustment mechanism 401. The braking force adjustment mechanism 401 is configured to allow a user to change the speed at which the plunger 207 is displaced (hereinafter referred to as the injection speed). The braking force adjustment mechanism 401 is operable to adjust the force (hereinafter referred to as the braking force) between the brake 221 and the plunger 207. Therefore, if the patient would prefer a slower injection, the braking force adjustment mechanism 401 can be used to reduce the injection speed, and vice versa. Therefore, the braking force adjustment mechanism 401 allows the user to control the injection speed according to their preferences. The braking force adjustment mechanism 401 can also be used to compensate for a specific viscosity of the medicament to be injected. For example, a medicament with a first viscosity will be injected at a first injection speed, while a medicament with a second viscosity will be injected at a second injection speed, wherein the second viscosity is higher than the first viscosity, wherein the second injection speed is slower than the first injection speed. Therefore, if the device is provided with a medicament with a relatively low viscosity, the user can adjust the braking force adjustment mechanism 401 to increase the braking force and maintain the injection speed as close as possible to their preferred injection speed. Likewise, if the device is provided with a medicament having a relatively high viscosity, the user can adjust the braking force adjustment mechanism 401 to reduce the braking force and maintain the injection speed as close as possible to their preferred injection speed. In one embodiment, information about the viscosity of the medicament and the corresponding setting of the braking force adjustment mechanism 401 are provided to the user to allow the user to select from a range of predetermined injection speeds.

[0080] 4, the braking force adjustment mechanism 401 includes a collar 4011 supported in a proximal region of the housing 201, overlapping 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. Rotation of the collar 4011 in one direction increases the injection speed, while rotation in the other direction decreases the injection speed, as will be explained further below.

[0081] Collar 4011 includes an outer surface 4012 that a user can grasp to rotate collar 4011 about longitudinal axis AA of device 10, and an inner surface 4013 that is configured to interact with detent 221. Rotation of collar 4011 in one direction presses detent 221 against plunger 207 with greater force.

[0082] The collar 4011 can be rotated between a first position representing the fastest injection speed and a second position representing the slowest injection speed.

[0083] In the first position, the brake 221 presses against the plunger 207 with the lowest force. In the second position, the brake 221 presses against the plunger 207 with the greatest force. Rotation of the collar 4011 between the first position and the second position changes the force with which the brake 221 presses against the plunger 207. Rotation of the collar 4011 toward the second position increases the force with which the brake 221 presses against the plunger 207. Thus, the collar 4011 can be rotated to fine-tune the injection speed to the patient's preference.

[0084] In this embodiment, the brake 221 is integrally formed with the housing 201 and includes at least one arm 2213 extending from the inner surface of the housing 201. In FIG. 4, two arms 2213 are shown, but it should be understood that the brake 221 may include a plurality of arms 2213 spaced around the inner surface of the housing 201.

[0085] The arm 2213 includes a hinge 2214 and a brake shoe 2215. The hinge 2214 extends away from the inner surface of the housing 201 in a cantilever manner and toward the plunger 207. The brake shoe 2215 extends from the end of the hinge 2214 in the longitudinal direction of the device 10. The brake shoe 2215 provides a brake surface 2216 configured to contact the outer surface 222 of the plunger 207.

[0086] In contrast to the braking surface 2216, the outer surface 2217 of the brake shoe 2215 contacts the inner surface 4013 of the lining 4011. 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 circumferential direction of the device 10. Therefore, when the lining 4011 is rotated, the contact pressure between the inner surface 4013 of the lining and the outer surface 2217 of the brake shoe 2215 varies according to the rotation direction of the lining 4011. If the lining 4011 is rotated in the direction of increasing thickness of the brake shoe 2215, the contact pressure between the inner surface 4013 of the lining and the outer surface 2217 of the brake shoe 2215 increases. Likewise, if the lining 4011 is rotated in the opposite direction, the contact pressure decreases.

[0087] Increasing the contact pressure between the inner surface 4013 of the lining and the outer surface 2217 of the brake shoe 2215 increases the force pressing the brake 221 against the plunger 207 .

[0088] The inner surface 4013 and the outer surface 4012 of the collar 4011 are connected to each other by at least one connecting portion 4014. The connecting portion 4014 extends through a slot 225 in the housing 201. The slot 225 extends in the circumferential direction to allow rotation of the collar 4011.

[0089] FIG5 shows a cross section of the brake force adjustment mechanism 401 of FIG4 taken transversely to the longitudinal axis of the device. In the embodiment illustrated in FIG5, the inner surface 4013 of the liner includes four ridges 4015 (in this case hemispherical protrusions of the inner surface 4013), each of which contacts the outer surface 2217 of a corresponding brake shoe 2215. The ridges 4015 and the brake shoe 2215 are arranged 90 degrees apart to evenly distribute the pressure applied to the outer surface 222 of the plunger 207. The connecting portions 4014 are also arranged 90 degrees apart and are located in corresponding slots in the housing (not shown).

[0090] In an alternative configuration of the embodiment of FIG. 4 , the ridge 4015 of the inner surface 4013 of the liner 4011 is omitted, and instead, the inner surface 4013 is smooth. In this configuration, the inner surface 4013 is provided with a gradient so that the thickness of the inner portion 4016 of the liner 4011 increases in the circumferential direction of the device 10. Therefore, when the liner 4011 is rotated, the contact pressure between the inner surface 4013 of the liner and the outer surface 2217 of the brake shoe 2215 varies according to the rotation direction of the liner 4011. If the liner 4011 is rotated in the direction of increasing thickness of the inner portion 4016 of the liner 4011, the contact pressure between the inner surface 4013 of the liner and the outer surface 2217 of the brake shoe 2215 increases. Likewise, if the liner 4011 is rotated in the opposite direction, the contact pressure decreases. In this configuration, the thickness of the shoe 2215 can be constant in the circumferential direction.

[0091] 6 , in which like features retain like reference numerals, the braking force adjustment mechanism 401 includes a sleeve 4017 supported in a proximal region of the housing 201, overlapping the plunger 207. The sleeve 4017 is slidably supported so 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 speed, while sliding the sleeve in the other direction decreases the injection speed, as will be explained below.

[0092] Sleeve 4017 includes an outer surface 4018 that a user can grip to slide sleeve 4017 along the longitudinal axis of device 10, and an inner surface 4019 that is configured to interact with detent 221. Sliding sleeve 4017 in one direction presses detent 221 against plunger 207 with greater force.

[0093] The sleeve 4017 is slidable between a first position indicating the fastest injection speed and a second position indicating the slowest injection speed.

[0094] In the first position, the brake 221 presses against the plunger 207 with minimal force. In the second position, the brake 221 presses against the plunger 207 with maximum force. Sliding the sleeve 4017 between the first position and the second position changes the force pressing the brake 221 against the plunger 207. Sliding the sleeve 4017 toward the second position increases the force pressing the brake 221 against the plunger 207. Thus, the sleeve 4017 slides to fine-tune the injection speed to the patient's preference.

[0095] 4 and 5, the brake 221 is integrally formed with the housing 201 and includes at least one arm 2213 extending from the inner surface of the housing 201. In FIG6, two arms 2213 are shown, but it should be understood that the brake 221 may include a plurality of arms 2213 spaced around the inner surface of the housing 201.

[0096] The arm 2213 includes a hinge 2214 and a brake shoe 2215. The hinge 2214 extends away from the inner surface of the housing 201 and toward the plunger 207. The brake shoe 2215 extends from the end of the hinge 2214 in the longitudinal direction of the device 10. The brake shoe 2215 provides a brake surface 2216 configured to contact the outer surface 222 of the plunger 207.

[0097] In contrast to 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 portion 4020 of the sleeve 4017 increases in the longitudinal direction of the device. Therefore, 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 slides. If the user slides the sleeve 4017 in the direction of increasing thickness of the inner portion 4020 of the sleeve 4017, the contact pressure between the inner surface 4019 of the sleeve and the outer surface 2217 of the brake shoe 2215 increases. Likewise, if the user slides the sleeve 4017 in the opposite direction, the contact pressure decreases.

[0098] 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 pressing the brake 221 against the plunger 207 .

[0099] 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 in the longitudinal direction of the device 10 to allow the sleeve 4017 to slide as described.

[0100] FIG7 shows a detail of an alternative configuration of the embodiment of FIG6 , in which 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 ridges 4023, which 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 slides. If the user slides the sleeve 4017 in the direction of increasing thickness of the brake shoe 2215, the contact pressure between the inner surface 4019 of the sleeve and the outer surface 2217 of the brake shoe 2215 increases. Likewise, if the user slides the sleeve 4017 in the opposite direction, the contact pressure decreases.

[0101] In the above embodiment, the high friction material area 223 may include a plurality of separate high friction material areas spaced apart around the outer surface 222 of the plunger 207, such that each separate high friction material area contacts the braking surface 2216 of the corresponding brake shoe 2215. For example, the plurality of separate areas 223 include four separate areas spaced apart by 90 degrees.

[0102] In the above embodiment, instead of the high friction material area 223, the plunger 207 may be alternatively provided with at least one channel 226 in its outer surface 222, as illustrated in FIG8 . 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 corresponding brake shoe 2215 covering the channel 226. The width of the channel 226 increases toward the proximal end P of the plunger 207. Therefore, the proportion of the braking surface 2216 of the brake shoe 2215 covering the channel 226 increases as the plunger 207 is displaced toward the end stop, thereby reducing the contact area between the outer surface 222 of the plunger 207 and the braking surface 2216. In addition, the varying width of the channel 226 causes an effective change in the deflection of the brake 221. These combined effects cause a corresponding reduction in the friction between the braking surface 2216 and the plunger 207, which compensates for the attenuation of the spring force. Therefore, the channel is configured to move the plunger 207 at a constant speed through its full range of motion between the initial position and the end stop position. It should be understood that in addition to / instead of changing the width of the channel 226, the friction between the braking surface 2216 and the plunger 207 can also be reduced by increasing the depth of the channel 226 toward the proximal end P of the plunger 207. Specifically, by increasing the depth of the channel 226, the contact pressure between the braking surface 2216 and the plunger is reduced. In this embodiment, at least a portion of the braking surface is located within the channel 226.

[0103] In the above embodiment, the at least one channel 226 may include a plurality of individual channels spaced around the outer surface 222 of the plunger 207, such that each individual channel is disposed below the braking surface 2216 of the corresponding brake shoe 2215. For example, the plurality of individual channels include four individual channels spaced 90 degrees apart.

[0104] In the above embodiment, the plunger 207 can be tapered so 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. Therefore, during displacement of the plunger 207, the contact force between the brake 221 and the plunger 207 decreases as the plunger is displaced toward the end stop position.

[0105] Embodiments of the injector devices described herein are configured to contain a medicament cartridge or a syringe pre-filled with a medicament.Herein, the term "medicament container" is intended to encompass both medicament cartridges and pre-filled syringes.

[0106] The term "drug" or "medicament" is used herein to describe one or more pharmaceutically active compounds. As described below, a drug or medicament may include at least one small molecule or macromolecule or a combination thereof in various types of formulations for treating 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 a molecular delivery system (such as a vector, plasmid or liposome). Mixtures of one or more of these drugs are also contemplated.

[0107] The term "drug delivery device" should encompass any type of device or system configured to distribute a drug into a human or animal body. Without limitation, the drug delivery device can be a syringe device (e.g., a syringe, a pen injector, an automatic injector, a large volume device, a pump, an infusion system, or other devices configured for intraocular, subcutaneous, intramuscular or intravascular delivery), a skin patch (e.g., osmotic, chemical, microneedle), an inhaler (e.g., nasal or pulmonary), an implantable (e.g., a coated stent, a capsule), or a feeding system for the gastrointestinal tract. Using a syringe device including a needle (e.g., a small gauge needle), the currently described drugs may be particularly useful.

[0108] The drug or medicament can be included in a primary package or "drug container" adapted for use with a drug delivery device. The drug container can be, for example, a cartridge, a syringe, a reservoir or other vessel, which is 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 can be designed to store the drug for at least one day (e.g., 1 day to at least 30 days). In some cases, the chamber can be designed to store the drug for about 1 month to about 2 years. Storage can occur at room temperature (e.g., about 20 ° C) or refrigerated temperature (e.g., from about -4 ° C to about 4 ° C). In some cases, the drug container can be or can include a dual-chamber cartridge, which is configured to store two or more components of a drug formulation (e.g., a drug and a diluent, or two different types of drugs) separately, one of which is stored in each chamber. In this case, the two chambers of the dual-chamber cartridge can be configured to allow mixing between the two or more components of the drug or medicament before and / or during distribution to the human or animal body. For example, the two chambers may be configured so that they are in fluid communication with each other (e.g., via a conduit between the two chambers) and allow the user to mix the two components when desired prior to dispensing. Alternatively or additionally, the two chambers may be configured to allow mixing when dispensing the components into the human or animal body.

[0109] Drug delivery devices and drugs described herein can be used to treat and / or prevent many different types of obstacles. Exemplary obstacles include, for example, diabetes or complications associated with diabetes (such as diabetic retinopathy), thromboembolic obstacles (such as deep vein or pulmonary thromboembolism). Other exemplary obstacles are acute coronary syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis.

[0110] Exemplary drugs for treating and / or preventing diabetes or complications associated with diabetes include insulin (e.g., human insulin, or human insulin analogs or derivatives); glucagon-like peptide (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 mixture thereof. As used herein, the term "derivative" refers to any substance that is structurally similar to the original substance so as to have substantially similar functions or activities (e.g., therapeutic effects).

[0111] Exemplary insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (glargine); 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.

[0112] Exemplary insulin derivatives are, 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-myristoylLysB28ProB29 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-lithocholyl-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: lixisenatide / AVE0010 / ZP10 / Lyxumia, exenatide / exendin-4 / Byetta / Bydureon / ITCA 650 / AC-2993 (a 39 amino acid peptide derived from Gila lizard monster), Liraglutide / Victoza, Semaglutide, Taspoglutide, Syncria / Albiglutide, Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / 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.

[0113] An exemplary oligonucleotide is, for example, mipomersen / Kynamro, a cholesterol-reducing antisense therapeutic used to treat familial hypercholesterolemia.

[0114] Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

[0115] Exemplary hormones include pituitary hormones or hypothalamic hormones or regulatory activity peptides and their antagonists, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, tocopherol), growth hormone (somatropin), desmopressin, terlipressin, gonadorelin, triptorelin, leuprorelin, buserelin, nafarelin and goserelin.

[0116] Exemplary polysaccharides include glucosaminoglycanes, 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-mentioned polysaccharides), and / or pharmaceutically acceptable salts thereof. The example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. The example of a hyaluronic acid derivative is Hylan GF 20 / Synvisc, which is a sodium hyaluronate.

[0117] As used herein, the term "antibody" refers to an immunoglobulin molecule or an antigen binding portion thereof. Examples of antigen binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments, which retain the ability to bind to antigens. The antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized antibody or a humanized antibody, a fully human antibody, a non-human antibody (e.g., a mouse antibody) or a single-chain antibody. In some embodiments, the antibody has effector functions and can fix complement. In some embodiments, the antibody has reduced or no ability to bind 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, for example, it has a mutagenic or missing Fc receptor binding region.

[0118] 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, which does not include a full-length antibody polypeptide, but still includes at least a portion of a full-length antibody polypeptide capable of binding an antigen. Antibody fragments can include cleavage portions of full-length antibody polypeptides, although the term is not limited to such cleavage fragments. Antibody fragments that can be used 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)), mini antibodies, chelated recombinant antibodies, triabodies or bibodies, intrabodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and antibodies containing VHH. Other examples of antigen-binding antibody fragments are known in the art.

[0119] The term "complementarity determining region" or "CDR" refers to short polypeptide sequences within the variable region 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 within the variable region of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the correct positioning of the CDR sequences to allow antigen binding. Although the framework region itself is typically not directly involved in antigen binding, as known in the art, certain residues within the framework region of certain antibodies may be directly involved in antigen binding, or may affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0120] 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).

[0121] The compounds described herein can be used in pharmaceutical formulations comprising (a) one or more compounds or pharmaceutically acceptable salts thereof, and (b) a pharmaceutically acceptable carrier. The compounds can also be used in pharmaceutical formulations comprising one or more other active pharmaceutical ingredients, or in pharmaceutical formulations in which the compounds of the invention or pharmaceutically acceptable salts thereof are the sole active ingredients. Thus, the pharmaceutical formulations of the present disclosure encompass any formulation prepared by mixing the compounds described herein and a pharmaceutically acceptable carrier.

[0122] It is also contemplated that pharmaceutically acceptable salts of any drug described herein may be used 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 with cations selected from alkali metals or alkaline earth metals, for example, Na+, or K+, or Ca2+, or ammonium ions N+(R1)(R2)(R3)(R4), wherein R1 to R4 represent, independently of one another, hydrogen, optionally substituted C1 C6-alkyl groups, optionally substituted C2-C6-alkenyl groups, optionally substituted C6-C10-aryl groups, or optionally substituted C6-C10-heteroaryl groups. Other examples of pharmaceutically acceptable salts are known to those skilled in the art.

[0123] Pharmaceutically acceptable solvates are, for example, hydrates or alkanolates, such as methanolate or ethanolate.

[0124] Those skilled in the art will appreciate that various modifications (additions and / or removals) may be made to the various components of the materials, formulations, apparatuses, methods, systems, and embodiments described herein without departing from the overall scope and spirit of the invention, and that the invention encompasses such modifications and any and all equivalents thereof.

Claims

1. A syringe device comprising: an outer shell for accommodating a drug container; and a drive mechanism for dispensing a medicament from a medicament container contained 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 drug container to dispense the drug; wherein the device further comprises a brake configured to control the rate of displacement of the plunger rod under the force of the displacement member; wherein the brake includes a braking surface that contacts 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; wherein the apparatus further comprises a braking force adjustment mechanism configured to adjust a contact pressure between the braking surface and the outer surface of the plunger rod; and wherein the braking force adjustment mechanism comprises a bushing rotatably mounted on the housing, the bushing being rotatable about the 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 being 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.

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

3. The syringe device of claim 2, wherein the proportion of the outer surface of the plunger that is covered by the high friction material increases toward the distal end of the plunger.

4. The syringe device of claim 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 toward the distal end of the plunger.

5. The syringe device of claim 1, wherein a region of the outer surface of the plunger is provided with a channel, the region being arranged to contact the brake surface of the brake during movement of the plunger between an initial position and an end stop position.

6. A syringe device according to claim 5, wherein the width and / or depth of the channel decreases towards the distal end of the plunger.

7. The syringe device of claim 1, wherein an inner surface of the collar contacts an outer surface of the stopper.

8. The syringe device of claim 7, wherein the outer surface of the stopper comprises a gradient such that the thickness of the stopper increases in a circumferential direction of the device, such that when the bushing is rotated, the contact pressure between the stopper surface and the outer surface of the plunger rod varies depending on the rotation direction of the bushing; or The inner surface of the liner includes a gradient so that the thickness of the inner portion of the liner increases in the circumferential direction of the device, so that when the liner is rotated, the contact pressure between the braking surface and the outer surface of the plunger rod changes according to the rotation direction of the liner.

9. The syringe device of claim 1, wherein an inner surface of the sleeve contacts an outer surface of the stopper.

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

11. An injector device according to any preceding claim, wherein the plunger rod is tapered such that the diameter of the distal end of the plunger rod is greater than the diameter of the proximal end of the plunger rod.

12. The syringe device of any one of claims 1-10, wherein the device further comprises a drug container.

13. The syringe device of any one of claims 1-10, wherein the displacement member comprises a spring.

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