Drug delivery device with laterally flexible needle sleeve

Abstract

A drug delivery device (20) is provided. The drug delivery device (20) comprises: a housing (22) for receiving a drug container (24); a needle sleeve (46) configured to be movable relative to the housing (22) in a first direction (80) from a first position to a second position; wherein the needle sleeve (46) comprises a first section (84) and a second section (86), the first section (84) being configured to move relative to the second section (86) in a second direction (82) perpendicular to the first direction (80) when the needle sleeve (46) is moved from the first position to the second position.

Description

background

[0001] This disclosure relates to a drug delivery device, particularly a very compact and easy-to-use drug delivery device.

[0002] In drug delivery devices, medication is typically delivered to the user via a needle that pierces the user's (or patient's) skin. The medication may be contained within a drug container of the drug delivery device, such as a syringe disposed within the device. Conventional drug delivery devices, including a syringe and an associated actuation mechanism, have a shape substantially corresponding to the shape of the syringe. In particular, conventional drug delivery devices including a syringe have an elongated cylindrical shape, wherein the axis of the drug delivery device may correspond to the axis of the needle. Such drug delivery devices are often referred to as pen-type devices. The cylindrical form can be difficult to manipulate, especially in cases where the user has some degree of motor impairment. Summary of the Invention

[0003] In the following text, the term "distal" refers to the direction in which the drug or agent is dispensed by the drug delivery device. Correspondingly, the term "proximal" refers to the opposite direction. Regarding pen-shaped drug delivery devices, the term "distal" refers to the direction toward the injection site and / or the tip of the needle of the device. Correspondingly, the term "proximal" refers to the direction away from the injection site and / or the tip of the needle of the device.

[0004] The purpose of this disclosure is to promote improvements associated with drug delivery devices, particularly in terms of size, shape, and operability.

[0005] This objective is achieved by the disclosed subject matter, for example, by the subject matter defined in the appended independent claims. Advantageous improvements and extensions are defined in the dependent claims and / or set forth in the description below.

[0006] One aspect of this disclosure relates to a drug delivery device. The drug delivery device includes: a housing for receiving a drug container; and a needle sleeve configured to be movable relative to the housing in a first direction from a first position to a second position; wherein the needle sleeve includes a first segment and a second segment, the first segment being configured to be movable relative to the second segment in a second direction perpendicular to the first direction when the needle sleeve moves from the first position to the second position. For example, the second direction may be a circumferential direction, such as the circumferential direction of the needle sleeve and / or the housing and / or the drug delivery device.

[0007] In one embodiment, the first segment and / or the second segment may have a closed circumference in at least a portion of the first segment and / or the second segment. In other words, the first segment and / or the second segment may include a portion having a closed circumference, such that in said portion, the first segment and / or the second segment extends along the entire circumference of the needle sleeve. In other words, the lateral surfaces of the first segment and / or the second segment may be closed in at least a portion of the first segment and / or the second segment.

[0008] In one embodiment, the first segment may be releasably connected to the second segment. The releasable connection may be configured to allow relative movement between the first segment and the second segment in at least one direction (e.g., circumferential and / or axial).

[0009] When the drug delivery device is positioned at the injection site, the second section of the needle sleeve may face the injection site, and the first section may face away from the injection site. The first and second positions of the needle sleeve may refer only to the position of the entire needle sleeve relative to a first direction, rather than the position of the first section relative to a second direction. The first position may be an initial position, and the second position may be an operational position. The initial position may be the position before the drug delivery device is pressed against the injection site. The operational position may be the position where the needle has pierced the injection site and is thus able to deliver the drug. In this case, the needle sleeve may be configured to protect the injection component of the drug delivery device in the initial position of the needle sleeve and to expose the injection component in the operational position of the needle sleeve.

[0010] Alternatively, the first position can be an operating position, and the second position can be a final position. In this case, the needle sleeve can be configured to protect the injection member in the final position of the needle sleeve. In the final position, the needle sleeve can be locked to prevent movement in the first direction. The injection member can be disposed within or on the housing, can be coupled to or be coupled to a drug container, and can be configured to inject a drug from the drug container into the injection site. The first direction can correspond to the axial direction of the drug delivery device.

[0011] The drug delivery device can be a full-function drug delivery device. The drug can be a pharmaceutical preparation. The drug delivery device can be an autoinjector. In an autoinjector, the energy for the drug delivery operation can be pre-stored in an energy storage component. That is, for example, when preparing the drug delivery device for use, the user does not need to provide the energy for the drug delivery operation. Instead, the energy can be pre-loaded into the drug delivery device by the manufacturer. For example, a drive spring (e.g., a helical spring or a flat helical spring) can be pre-stressed or pre-biased to provide the energy for the drug delivery operation.

[0012] The housing can be mushroom-shaped, comprising a main shaft and a cap on the main shaft. One advantage of this mushroom shape is its compact and convenient design. The main shaft provides a supporting surface for contact with the user's skin during dispensing. During dispensing, the cap faces away from the injection site. The main shaft provides sufficient space to accommodate a drug container, such as a syringe. The cap provides a comfortable gripping area opposite the supporting surface (i.e., facing away from the user's skin during use). Therefore, the mushroom-shaped design offers a very large gripping area compared to cylindrical drug delivery devices. This large gripping area also makes the drug delivery device easier for patients with limited dexterity to hold, such as those with rheumatism.

[0013] In one embodiment, the first segment and the second segment are flexibly connected to each other by a flexible connector and are configured such that when the needle sleeve moves from the first position to the second position, the first segment rotates and the second segment is fixed to prevent rotation. The flexible connector can flex, such that potential energy is stored within the flexible connector when the needle sleeve moves from the first position to the second position.

[0014] In one embodiment, the flexible connector can releasably connect the first segment and the second segment.

[0015] In one embodiment, the flexible coupling includes a torsion spring between the first and second segments. The torsion spring can be biased when the first segment moves relative to the second segment in a second direction or in the opposite direction. For example, the torsion spring can be biased by rotation of the first segment relative to the second segment.

[0016] In one embodiment, the flexible connector includes at least one flexible rod. The flexible rod can be configured to be biased when the first segment moves relative to the second segment in a second direction or vice versa. The flexible connector of the needle sleeve, particularly the needle sleeve, can include two or more flexible rods connecting the first and second segments to each other. When the first segment moves in the second direction, the flexible rod can bend. When the flexible rod bends, it is biased and energy is stored within the bent flexible rod. For example, when the needle sleeve moves in the first direction or vice versa (e.g., from a first position to a second position), the flexible rod can bend in the circumferential direction.

[0017] In one embodiment, the drug delivery device includes at least two flexible rods, as described above, wherein these flexible rods are separated from each other by through recesses within the needle sleeve. Preferably, the needle sleeve may include more than two flexible rods, wherein adjacent flexible rods may be separated by corresponding through recesses within the needle sleeve. For example, the needle sleeve may include 3, 4, 5, 7, 10, 15, 20, 25, 30, 40, 50 or even more flexible rods separated by through recesses.

[0018] In one embodiment, the flexible bar and the through recess may be arranged alternately around at least a portion of the circumference of the needle sleeve. For example, the flexible bar and the through recess may be arranged to cover at least 5% of the circumference of the needle sleeve, i.e., 5% of 360 degrees. For example, the flexible bar and the through recess may be arranged to cover at least or exactly 5%, 10%, 20%, 30%, 50%, 60%, 70%, 80%, or 90% of the circumference of the needle sleeve in the circumferential direction. In one embodiment, the flexible bar and the through recess may be arranged alternately around the entire circumference of the needle sleeve.

[0019] In one embodiment, the angular offset between the two flexible rods caused by the through recess therebetween can be less than or equal to 180 degrees. For example, the angular offset between the two flexible rods caused by the through recess therebetween can be less than or equal to 150 degrees, 135 degrees, 120 degrees, 90 degrees, 45 degrees, 30 degrees, 15 degrees, 10 degrees, 9 degrees, 6 degrees, 5 degrees, or less than 5 degrees, such as 4 degrees, 3 degrees, 2 degrees, or 1 degree.

[0020] In one embodiment, the angle covered by the flexible rod can correspond to the angle covered by the through recess. In other words, the flexible rod and the through recess can cover the same distance in the circumferential direction of the needle sleeve. Alternatively, the flexible rod can extend to cover an angle greater or less than the circumferential extension of the through recess.

[0021] In one embodiment, the needle sleeve is made from a single piece. Specifically, the first and second segments, as well as the flexible connector (e.g., a flexible rod), can be made from the same material. In other words, the needle sleeve, particularly the first and second segments and the flexible connector, can be integrally formed.

[0022] In one embodiment, the first segment is coupled to the housing via a guide interface. The guide interface can be configured such that when the needle sleeve moves in a first direction, the first segment is moved in a second direction via the guide interface. The guide interface may include a guide element and a guide member. The guide element may be disposed at the first segment, and the guide member may be disposed at the housing, or vice versa. The guide element and guide member can be configured such that when the needle sleeve moves in the first direction, the first segment is guided within the guide member by the guide element, thereby allowing movement in the second direction. For example, the guide element may include a guide pin. The guide pin may extend in a direction perpendicular to the first direction. For example, the guide pin may extend in a radial direction. For example, the guide member may include a first channel in which the guide pin is disposed and guided. For example, starting from a first position of the needle sleeve, the first channel may extend obliquely in both the first and second directions, such that when the needle sleeve is pushed in the first direction, the first segment is pushed in the second direction. This movement of the first segment relative to the second segment can bias a flexible connector (e.g., a flexible rod).

[0023] In one embodiment, the guide interface is configured such that when the needle sleeve is in its operating position, relaxation of the flexible coupling allows the first segment to move in a direction opposite to the second direction. For example, after extending obliquely in both the first and second directions, the first channel can extend in a direction opposite to the second direction, for example, in the form of a bend. This shape of the first channel allows the flexible coupling to relax as the guide element (e.g., the guide pin) reaches the bend due to further movement of the needle sleeve in the first direction. Relaxation of the flexible coupling allows the first segment to move in a direction opposite to the second direction because the guide pin can move within the first channel in a direction opposite to the second direction. In other words, the guide pin can move along the bend, thereby allowing the first segment to move in the opposite direction to the second direction.

[0024] In one embodiment, the guide interface is configured such that when the needle sleeve moves from its second position to a third position in a direction opposite to the second direction, the first segment is further moved via the guide interface. For example, when the first segment moves further in the direction opposite to the second direction, the flexible connector (e.g., a flexible rod) can be bent and / or biased. Specifically, when the needle sleeve moves from its first position to its second position, the flexible connector can flex in another direction. The third position can be the final position of the needle sleeve. In this case, the second position can be the operating position, and the first position can be the initial position. In the final position, the injection member can be protected by the needle sleeve, for example, permanently. In other words, the injection member can be kept away from user touch.

[0025] In one embodiment, the guiding interface is configured such that when the needle sleeve moves toward its final position—for example, before the needle sleeve reaches its final position, or when the needle sleeve reaches its final position—the first segment is moved in a second direction by relaxation of the flexible coupling. When the needle sleeve is in its final position, the flexible coupling (e.g., a flexible rod) can relax, and the first segment can be in its corresponding final position relative to the second segment. The flexible coupling can relax completely or only partially, such that some energy can still be stored in the flexible coupling when the needle sleeve is in its final position. This can be advantageous for preventing movement of the first segment relative to the second segment in a direction opposite to the second direction. In other words, this can be advantageous for holding the first segment in its final position.

[0026] In one embodiment, the guide interface includes an engagement element, and a first segment is configured to engage the engagement element when the needle sleeve reaches its third position, such that the needle sleeve is locked in the third position and prevents movement toward the second position. For example, the guide includes an engagement element at or within the guide. In this case, when the needle sleeve reaches its third position, the guide element engages with the engagement element, such that the needle sleeve is locked in the third position and prevents movement toward the second position. The engagement element may be a hook-shaped segment at or within the guide. The guide element may be configured to engage at the hook-shaped segment when a flexible coupling (e.g., a flexible rod) is at least partially relaxed.

[0027] In one embodiment, the guiding interface includes a guiding element and a guide for guiding the guiding element, or comprises thereof. For example, the guiding element may be disposed at a first section, and the guide may be disposed at a housing. The guiding element may include a guide pin, or comprises thereof. The guide may include a first channel, or comprises thereof, in which the guide pin is disposed and guided.

[0028] In one embodiment, the drug delivery device includes a second channel within the housing. The second channel may extend only in the first direction. The second segment may include a torsion protector. The torsion protector and the second channel may be configured to interact to limit movement of the second segment in a second direction or the opposite direction when the needle sleeve moves in the first direction. For example, the torsion protector and the second channel may be configured to interact such that when the needle sleeve moves in the first direction, the torsion protector moves within the second channel in the first direction and fixes the second segment to prevent movement in the second direction or the opposite direction.

[0029] In one embodiment, the second channel may extend in a first direction and a second direction, thereby allowing the second segment to move in the second direction or the opposite predefined direction when the needle sleeve moves in the first direction.

[0030] In one embodiment, the second channel may extend from the distal end of the needle sleeve to a flexible connector, such as the one or more flexible rods. Alternatively or additionally, the second channel may extend in the first direction along a portion of the second segment, for example, less than 90% of the length of the second segment. For example, the second channel may extend in the first direction along less than or exactly 80%, 75%, 70%, 60%, 50%, 40%, 30%, 25%, 20%, 10%, or 5% of the length of the second segment.

[0031] In one embodiment, the angular position of the second channel can be such that if the second channel extends to the flexible connector, the second channel is aligned with one of the through recesses.

[0032] In one embodiment, the housing may include more than one previously described second channel, such as two, three, four, or six second channels. These second channels may be equidistantly positioned about the circumferential direction. The second section may include a corresponding number of torsion guards for interacting with the second channels as described above.

[0033] In one embodiment, the drug delivery device includes an injection member for injecting a drug into an injection site. For example, the injection member may include, or be composed of, a needle for injecting a drug into an injection site. Alternatively, the injection member may include, or be composed of, a nozzle for injecting a drug into an injection site under high pressure.

[0034] In one embodiment, the drug delivery device includes a needle sleeve spring coupled to or connectable to a needle sleeve and configured to move the needle sleeve in a direction opposite to a first direction when the drug delivery device is removed from the injection site, for example, after injection, or if the user removes the drug delivery device from the injection site beforehand. For example, the spring force of the needle sleeve spring may need to be overcome to push the needle sleeve from its initial position to its operating position when the drug delivery device is pressed against the injection site.

[0035] In one embodiment, the drug delivery device includes a drug container within a housing and a drug within the drug container. The drug container may be coupled to or can be coupled to an injection component.

[0036] It should be noted that the features described above and below in conjunction with different embodiments or aspects can be combined with each other, even if such combinations are not expressly disclosed herein. Further features, advantages, and conveniences of this disclosure, and in particular the proposed concepts, will become clear from the following description of exemplary embodiments in conjunction with the accompanying drawings. Attached Figure Description

[0037] Figure 1A side cross-sectional view of the interior of an exemplary embodiment of the drug delivery device in a first state is shown.

[0038] Figure 2 Demonstrated in the second state Figure 1 A side cross-sectional view of the interior of a drug delivery device.

[0039] Figure 3 Showing Figure 1 A bottom view of an exemplary embodiment of the energy storage component of a drug delivery device.

[0040] Figure 4 Demonstrates the third state Figure 1 A side cross-sectional view of the interior of a drug delivery device.

[0041] Figure 5 Demonstrates the fourth state Figure 1 A side cross-sectional view of the interior of a drug delivery device.

[0042] Figure 6 Demonstrates the fifth state Figure 1 A side cross-sectional view of the interior of a drug delivery device.

[0043] Figure 7 A side cross-sectional view of the interior of an exemplary embodiment of a drug delivery device is shown.

[0044] Figure 8 A side cross-sectional view of the interior of an exemplary embodiment of a drug delivery device is shown.

[0045] Figure 9 A perspective view showing an exemplary embodiment of a drug delivery device and a user's hand holding the drug delivery device.

[0046] Figure 10 An exemplary embodiment of the needle sleeve and main rod in a first state is shown.

[0047] Figure 11 Demonstrated in the second state Figure 10 The needle sleeve and main shaft.

[0048] Figure 12 Demonstrates the third state Figure 10 The needle sleeve and main shaft.

[0049] Figure 13 Demonstrates the fourth state Figure 10 The needle sleeve and main shaft.

[0050] Figure 14 Demonstrates the fifth state Figure 10 The needle sleeve and main shaft.

[0051] Figure 15 Demonstrates the sixth state Figure 10 The needle sleeve and main shaft.

[0052] Figure 16 shows the expanded structural formula, molecular formula, and molecular weight of phenotype. Detailed Implementation

[0053] In the accompanying drawings, the same elements, elements of the same kind, and elements that function in the same or similar manner may be labeled with the same reference numerals.

[0054] Figure 1 A side cross-sectional view of the interior of an exemplary embodiment of the drug delivery device 20 in its first state is shown. Specifically, Figure 1 A drug delivery device 20 in its initial state, for example, delivered by a manufacturer, is shown. The drug delivery device 20 includes a housing 22. The housing 22 is held and / or provided for holding a drug container 24. The shape and / or size of the housing 22 may correspond to the shape and size of a large mushroom, including a main stem 21 and a cap 23. The mushroom-shaped housing may be substantially rotationally symmetrical about an axis 45. The axis 45 may be the central axis of the drug delivery device 20.

[0055] A drug container 24 may be at least partially disposed within a main stem 21, for example, within a container inlet 25 of the main stem 21. The drug container 24 includes a dispensing end 28 and a distal end 30 opposite to the dispensing end 28. As shown, the distal end may be offset proximally from the container inlet 25 (e.g., its proximal-facing surface 25.1). The drug container 24 includes a chamber 26. A drug or pharmaceutical preparation (e.g., a liquid preparation) may be disposed within the chamber 26. The chamber 26 is fluid-tightly closed by a stopper 32. The stopper 32 is movably held within the drug container 24 and may seal the drug container toward the distal end 30 of the drug container 24. The stopper 32 may be displaced at the dispensing end 28 toward an outlet of the drug container 24 to dispense the drug held within the chamber 26 through the outlet. In particular, the stopper 32 may be moved toward the dispensing end 28 in a dispensing direction 40. If the stopper 32 moves in the dispensing direction 40, the drug is dispensed at the dispensing end 28 through the outlet. The distribution direction 40 can be parallel to axis 45.

[0056] The outlet of the drug container 24 at the dispensing end 28 may include an injection member. The injection member may be connected to the outlet, for example, the injection member may be retained within the outlet. The injection member may fluidly connect the chamber 26 to the outside of the drug container 24. For example, the injection member may be a needle 27. Alternatively, the injection member may define the outlet. For example, the injection member may include, or may consist of, a nozzle. The needle 27 may be a component of the drug container 24 (e.g., (permanently or releasably) attached to the drug container body) or separate from the drug container 24. In the first case, the drug container 24 may be an syringe. In the second case, the drug container 24 may be a cartridge. When a cartridge is used as the drug container 24, initially, the drug container 24 and the needle 27 may be fluidly separated, and fluid communication may only be established between the interior of the drug container 24 and the needle 27 during operation of the drug delivery device 20. Furthermore, instead of a single needle 27, two or more separate needles may be arranged, one needle (e.g., needle 27) for piercing the skin, and at least one other needle (not shown) for piercing the septum of the drug container 24, wherein the at least one other needle is configured to communicate with the needle 27 for piercing the skin.

[0057] A drive mechanism for driving the drug delivery operation is suitably disposed in the housing 22. The drive mechanism includes: a plunger rod arrangement 35 for driving the plug 32 of the drug container 24 in the dispensing direction 40; a drive member 39 for driving the plunger rod arrangement 35; and an energy storage member 42 coupled to the drive member 39 to rotate the drive member 39.

[0058] The plunger rod arrangement 35 can be connected to the plug 32 via a bearing 34. The plunger rod arrangement 35 can be configured as a telescopic plunger rod arrangement 35. The telescopic plunger rod arrangement 35 may include several sections, such as a first section 37, a second section 38, and optionally more corresponding sections (not shown). The first section 37 can be connected to the plug 32 via a bearing 34. In particular, the first axial end (e.g., the distal end) of the first section 37 can be connected to the bearing 34, specifically to the ball head 36 of the bearing.

[0059] The drive member 39 can be coupled to the housing 22 via a retainer. The retainer can be configured as a suspension. The suspension can be configured to retain the drive member 39 such that the drive member 39 is fixed axially in the distribution direction 40 and conversely, and the drive member 39 can rotate about axis 45. The drive member 39 is coupled to the plunger rod arrangement 35 via a threaded interface. The threaded interface is configured such that rotation of the drive member 39 causes translational movement of the plunger rod arrangement 35, particularly the first segment 37 and the second segment 38, in the distribution direction 40. In particular, the second segment 38 can be operatively coupled to the first segment 37 and the drive member 39 such that rotation of the drive member 39 can be converted by the second segment 38 into translational movement of the first segment 37 in the distribution direction. In particular, the second segment 38 can be operatively coupled to the first segment 37 and the drive member 39 such that rotation of the drive member 39 is primarily converted into translational movement of the second segment 38 in the distribution direction 40. The first segment 37 can translate together with the second segment 38. At the end of the translation of the second segment 38, the drive member 39 can rotate the second segment 38. The rotation of the second segment 38 can cause a further translation of the first segment 37 in the distribution direction 40.

[0060] The threaded interface may include a first threaded interface and a second threaded interface. The first threaded interface may be configured to operatively engage a first segment 37 to a second segment 38. The second threaded interface may be configured to operatively engage the second segment 38 to a drive member 39. The first threaded interface may include a first interface feature at the first segment 37 and a second interface feature at the second segment 38, the first interface feature engaging with the second interface feature. Alternatively or additionally, the second threaded interface includes a third interface feature at the second segment 38 and a fourth interface feature at the drive member 39, the third interface feature engaging with the fourth interface feature. The first interface feature may be a first thread. Alternatively or additionally, the second interface feature may be a second thread. Alternatively or additionally, the third interface feature may be a third thread. Alternatively or additionally, the fourth interface feature may be a fourth thread. In other words, at least one of the first and second interface features may be a thread, and / or at least one of the third and fourth interface features may be a thread. For example, each interface feature may be a thread. Alternatively, the interface feature that interacts with the corresponding thread of the same threaded interface but is not a thread may include one or more bars or pins that engage with the corresponding thread and can provide the same or equivalent functionality as the thread. Each thread may include one, two, or more turns. If one of the threads includes two or more turns, the start and / or end points of the corresponding turns may be axially offset from each other. These threads may have different pitches to manipulate injection speeds, and in particular to provide different injection speeds. Specifically, a first pitch may be provided in the first thread, and a second pitch may be provided in the second thread, wherein the first pitch may be greater than the second pitch.

[0061] The second segment 38 and the drive member 39 can be configured such that rotation of the drive member 39 is converted into translational movement of the second segment 38 until the end of the third thread and / or the end of the fourth thread is reached, and further rotation of the drive member 39 can be converted into rotation of the second segment 38. For example, the second segment 38 and the drive member 39 can be configured such that rotation of the drive member 39 is converted into translational movement of the second segment 38 until the end of the third thread of the second segment 38 reaches the end of the fourth thread of the drive member 39, and further rotation of the drive member 39 can be converted into rotation of the second segment 38.

[0062] The drive member 39 has an axially extending drive member recess, and the second segment 38 has an axially extending second segment recess. The second segment 38 is disposed within the drive member recess, and the first segment 37 is disposed within the second segment recess. In this case, the first thread at the first segment is an external thread, the second thread at the second segment is an internal thread, the third thread at the second segment is an external thread, and the fourth thread at the drive member is an internal thread. The drive member recess and / or the second segment recess are each through recesses extending through the drive member and / or the second segment, respectively. Alternatively, the drive member recess and / or the second segment recess may be closed at their ends facing away from the plug 32.

[0063] Alternatively, the first segment 37 may have an axially extending first segment recess, and the second segment 38 may have an axially extending second segment recess, wherein the second segment 38 may be disposed within the first segment recess, and the drive member 39 may be disposed within the second segment recess (not shown). In this case, the first thread at the first segment is an internal thread, the second thread at the second segment is an external thread, the third thread at the second segment is an internal thread, and the fourth thread at the drive member is an external thread. Each of these segment recesses may be a through recess extending through the corresponding segment. Alternatively, these segment recesses may be closed at their ends facing the plug 32.

[0064] The energy storage member 42 may be a flat helical spring coupled to the drive member 39. Other possible drive energy sources, other than the spring, may include a single battery cell or battery for driving the plunger rod arrangement 35 via a motor, or (where gas pressure can be used to drive the drug delivery operation) a reservoir suitable for providing gas pressure. The flat helical spring may be loaded and locked in the initial state of the drug delivery device 24. The energy storage member 42 is coupled to the drive member 39. In the initial loaded state, energy is stored in the loaded energy storage member 42, i.e., the flat helical spring is biased. If the energy storage member 42 is released, the energy stored in the energy storage member 42 is released and transferred to the drive member 39, causing the drive member 39 to rotate. If the drive member 39 rotates, the rotation is transmitted to the plunger rod arrangement 35 via a threaded interface (e.g., a first threaded interface).

[0065] The drive member 39 can be coupled to the energy storage member 42 such that locking of the rotatable member 39 corresponds to locking of the energy storage member 42. Therefore, if the drive member 39 is held in its initial state, the energy storage member 42 can also be held in its initial state. To hold the drive member 39 in its initial state, the drug delivery device 20 may include a retainer 44. The retainer 44 can be configured to lock the energy storage member 42 in its initial state. The retainer 44 can be operatively coupled to the needle sleeve 46 such that the retainer 44 releases the energy storage member 42 when the needle sleeve 46 is moved into the housing 22. The retainer 44 can be coupled to the housing 22 and can be movable relative to the housing 22, for example, rotatable.

[0066] The needle sleeve 46 may be arranged to protect the needle 27 of the drug delivery device 20. The needle sleeve 46 may project distally from the housing 22 in an initial state. The needle sleeve 46 may move relative to the housing 22 from an initial position or from a first position in the initial state to a second position or a triggered position. The needle sleeve 46 may provide a support surface for contact with the injection site during dispensing operations, the support surface facing away from the cap 23. The needle sleeve 46 may include a release member 56 for operating the retainer 44. The release member 56 may be formed as a protrusion projecting radially, preferably radially outward, from the needle sleeve 46, for example, at the proximal end of the needle sleeve 46. The release member 56 may be formed on the side of the needle sleeve 46 facing away from the support surface.

[0067] The needle sleeve 46 can be configured to extend beyond the tip of the needle 27, which can protrude from the bottom of the housing 22 before the drug delivery operation begins. The needle sleeve 46 can be movably arranged within the main shaft 21. In particular, the needle sleeve 46 can move parallel to axis 45 and can therefore be further introduced into the main shaft 21. During this movement, for example before the needle sleeve 46 reaches a second position, the needle 27 can pierce the user's skin. When the drug delivery device 20 is pressed against the injection site (e.g., the user's skin), the needle sleeve 46 can move relative to the main shaft 21, for example, within the main shaft 21 in a proximal direction. In particular, if the drug delivery device 20 is positioned on the skin, with the bottom surface of the main shaft 21 in contact with the skin, the needle sleeve 46 is pushed into the main shaft 21. If the needle sleeve 46 is pushed into the main shaft 21, the needle 27 is exposed and can pierce the skin. The bottom surface of the main rod 21 can provide at least a portion of a support surface for contact with the injection site during the dispensing operation.

[0068] The needle sleeve 46 can be used as a triggering member of the drug delivery device 20. For example, when the needle sleeve 46 is removed from... Figure 1 and Figure 2The initial or first position depicted in the diagram moves to its second or trigger position (see [reference]). Figure 4 and Figure 5 When the needle sleeve 46 is moved into the main rod 21, the needle sleeve can initiate the drug delivery operation. Specifically, the needle sleeve 46 can be configured to release the retainer 44 when moving from a first position to a second position or when in the second position. Release of the retainer 44 can initiate the drug delivery operation. In one embodiment, release of the retainer 44 may only be possible when the needle sleeve 46 is in the second position. In one embodiment, if the needle sleeve 46 moves into the main rod 21, the release member 56 can act on the retainer 44, causing the retainer 44 to release the locked and biased energy storage member 42. The energy storage member 42 then causes the drive member 39 to rotate, causing the first segment 37 and thus the plug 32 to move in the dispensing direction 40. Therefore, the plug 32 can only move when the drug delivery device 20 presses against the injection site with a force sufficient to move the needle sleeve 46 relative to the main rod 21, thus exposing the needle 27.

[0069] The needle 27 can be protected by a needle shield 50 before its use. The needle shield 50 can cover the needle 27 until it is removed, for example, manually by a user. The needle shield 50 may include an engagement device 52 that can interact with an engagement recess 54 of the needle sleeve 46. For example, the engagement device 52 may include one or more protrusions and / or pins that can be arranged within the engagement recess 54 for securing the needle shield 50 to the needle sleeve 46. The needle shield 50 can be removed from the needle sleeve 46 by rotating the needle shield 50 relative to the needle sleeve 46 and by removing the engagement device 52 from the engagement recess 54 at the end of the rotation. The needle shield 50 may include a ring 59 facing away from the needle sleeve 46. The ring 59 can provide a comfortable gripping structure for holding and removing the needle shield 50. Alternatively, a cap-gripper-needle shield configuration may be provided, and / or the needle shield 50 and ring 59 may be configured such that the needle shield 50 can be easily removed by pulling the ring 59, in particular without any rotation.

[0070] The gripping ring 58 may be disposed at the cap 23 and / or at least partially disposed inside the cap. For example, the cap 23 may provide a recess in which the gripping ring 58 is disposed, such that at least the outer portion of the gripping ring 58 may protrude from the recess. The gripping ring 58 may comprise a material that provides strong friction when gripped by a user's hand. The gripping ring 58 may comprise rubber or may be made of rubber.

[0071] The drug delivery device 20 is an autoinjector. The drug delivery device 20 can be a single-shot device, i.e., it is configured to dispense only one dose. The drug delivery device 20 can be a disposable drug delivery device, i.e., a drug delivery device 20 that is discarded after use. The drug container 24 and / or needle 27 can be secured within the drug delivery device 20, for example, within the housing 22. Therefore, the user may have to perform the movement of piercing the skin with the needle 27 by placing the drug delivery device 20 on the skin.

[0072] Figure 2 Demonstrated in the second state Figure 1 A side cross-sectional view of the interior of the drug delivery device 20. In the second state, the needle sleeve 46 remains in its initial position. However, in the second state, the needle shield 50 is removed from the needle 27 and the needle sleeve 46.

[0073] Figure 3 Showing Figure 1 and Figure 2 A bottom view of an exemplary embodiment of the energy storage member 42 of the drug delivery device 20. In particular, Figure 3 The drug delivery device 20 was shown along Figure 2 The bottom view of the cross-section of line III shown. From Figure 3 As can be seen, the energy storage member 42 may include a hook 60, which is hooked into a corresponding hook recess of the drive member 39. The rotational force provided by the energy storage member 42 can be transmitted as rotational movement of the drive member 39 through the hook 60.

[0074] Figure 4 Demonstrates the third state Figure 1A side cross-sectional view of the interior of the drug delivery device 20. In the third state, the needle sleeve 46 is in its second position and the retainer 44 is triggered. For example, the needle sleeve 46 has moved to its second position by placing the drug delivery device 20 on the injection site and by biasing the needle sleeve spring 48 by pressing the drug delivery device 20 against the injection site while overcoming the force of the needle sleeve spring 48. In this third state, the retainer 44 is triggered, causing it to release the energy storage member 42. Thus, in the third state, the energy of the energy storage member 42 is at least partially released, causing the energy storage member 42 to rotate the drive member 39. As shown, the drive member 39 rotates such that the second segment 38 moves in the dispensing direction 40 by the rotation of the drive member 39 until it reaches the end of the range of the second threaded interface (e.g., the third interface feature and / or the fourth interface feature), and the second segment 38 may not be able to translate further. Due to the connection between the first segment 37 and the second segment 38, the first segment 37 moves together with the second segment 38 in the dispensing direction 40. Furthermore, in the third state, the first segment 37 moves the plug 32 in the dispensing direction 40, thereby performing the dispensing operation. At a point when the second segment 38 may be unable to move further, the second segment 38 begins to rotate.

[0075] Figure 5 Demonstrates the fourth state Figure 1 A side cross-sectional view of the interior of the drug delivery device 20. In the fourth state, the second segment 38 has been rotated by the rotation of the drive member 39. If the second segment 38 rotates, the first segment 37 translates in the dispensing direction 40 due to the first threaded interface. Specifically, in the fourth state, the first segment 37 has translated to the point that the stopper 32 has completed its entire stroke and may not be able to move further in the dispensing direction 40. Therefore, in the fourth state, the dispensing operation has reached its end point, and a given dose of drug has been dispensed.

[0076] Figure 6 Demonstrates the fifth state Figure 1 A side cross-sectional view of the interior of the drug delivery device 20. In the fifth state, the drug delivery device 20 has been removed from the injection site. The needle sleeve 46 is pushed out of the main rod 21 by the force of the needle sleeve spring 48, so that the needle sleeve 46 protects the needle 27. The main rod 21 and the needle sleeve 46, which guide the needle sleeve 46, can be configured such that after the dispensing operation is completed and the drug delivery device 20 is removed from the injection site, the needle sleeve 46 cannot be pushed back into the main rod 21. The following text regarding... Figures 10 to 13 The corresponding structure has been explained.

[0077] Figure 7A side cross-sectional view of the interior of an exemplary embodiment of the drug delivery device 20 is shown. Figure 7 The drug delivery device shown generally corresponds to the drug delivery device 20 described above. Therefore, only the following discussion focuses on this. Figure 7 The drug delivery device 20 shown differs from the drug delivery device 20 described above in the following features: The drug delivery device 20 includes a stabilizing cone 62. The stabilizing cone 62 projects radially outward from the needle sleeve 46 in a distal direction. The stabilizing cone 62 provides an additional support surface that is larger than the support surface of the needle sleeve 46. Therefore, these two support surfaces together provide an even larger support surface, allowing the drug delivery device 20 to be positioned more stably at the injection site.

[0078] Figure 8 A side cross-sectional view of the interior of an exemplary embodiment of the drug delivery device 20 is shown. Figure 8 The drug delivery device 20 shown generally corresponds to one of the drug delivery devices 20 described above. Therefore, only one will be discussed below. Figure 8 The features of the drug delivery device 20 shown are different from those of the drug delivery device 20 described above. Figure 8 The main shaft 21 of the drug delivery device 20 is tapered and includes a large support surface at its distal end, which faces the injection site if the drug delivery device 20 is positioned over an injection site. Specifically, at its distal end, the tapered main shaft 21 includes a radially extending protrusion, preferably extending radially inward, which provides a larger support surface than the support surface of the needle sleeve 46. Together, these two support surfaces provide an even larger support surface, which facilitates a more stable placement of the drug delivery device 20 over the injection site.

[0079] Figure 9 A perspective view showing an exemplary embodiment of the drug delivery device 20 and a user's hand 66 holding the drug delivery device 20. Figure 9 The drug delivery device 20 shown may correspond to one of the drug delivery devices 20 described above. Therefore, only those features not discussed above will be discussed below. The drug delivery device 20 may include finger recesses 64 at the cap 23. The finger recesses 64 may be configured to place at least some of the fingers of a user's hand 66 on the cap 23. The finger recesses 64 facilitate easy and comfortable manipulation of the drug delivery device 20.

[0080] Figure 10 An exemplary embodiment of the needle sleeve 46 and the main rod 21 in a first state is shown. Specifically, Figure 10A side view of the needle sleeve 46 and a cross-sectional side view of the main shaft 21 are shown in the first state. In the first state of the needle sleeve 46, the drug delivery device 20 is not yet placed on the user's skin, and the needle sleeve 46 protects the needle 27. In the first state, the needle sleeve 46 is in its first position. The needle sleeve 46 is configured to be relative to the housing 22 in a first direction 80 (see...). Figure 11 and Figure 12 Move from the first position to the second position (see...) Figure 12 ).

[0081] The needle sleeve 46 includes a first segment 84 and a second segment 86. During drug dispensing operations, the second segment 86 may face the injection site, and the first segment 84 may face away from the injection site. The first segment 84 is configured to be positioned relative to the second segment 86 in a second direction 82 perpendicular to the first direction 80 (see [link to original text]) when the needle sleeve 46 moves from a first position to a second position. Figure 11 The first segment 84 and the second segment 86 can be flexibly connected to each other by a flexible coupling. The first segment 84 and the second segment 86 can be configured such that when the needle sleeve 46 moves from the first position to the second position, the first segment 84 rotates, particularly in the second direction 82, and the second segment 86 is fixed to prevent rotation.

[0082] The first segment 84 can be connected to the housing 22 via a guide interface. The guide interface may include a guide pin 90 of the needle sleeve 46 and a guide of the housing 22. The needle sleeve 46 includes a guide pin 90 at the first segment 84, a torsion protection member 92 at the second segment 86, and at least one (preferably two or more) flexible rods 94 that flexibly connect the first segment 84 to the second segment 86. Thus, for example, the flexible connection between the first segment 84 and the second segment 86 can be provided by the flexible rods 94. The guide pin 90 may protrude radially outward from the outer wall of the needle sleeve 46. Adjacent flexible rods 94 may be separated by a through recess 88 extending through the wall of the needle sleeve 46. The flexible rods 94 and the body of the needle sleeve 46 may be made from one piece, particularly from the same material. The torsion protection member 92 may include a direction parallel to the first direction 80 (i.e., in...). Figure 12 A rod that extends vertically in the middle.

[0083] The main shaft 21 of the housing 22 may include a guide. This guide may include a first channel 96 and a second channel 104. For ease of explanation regarding the interaction between the main shaft 21 and the needle sleeve 46, the first channel 96 may be referred to as the guide. When viewed from the distal end of the main shaft 21, the first channel 96 may initially extend parallel to a first direction 80. In an intermediate section, the first channel 96 may include an inclined portion relative to the first direction 80, and then the first channel again extends parallel to the first direction 80 toward a bend 98. The bend 98 may form the proximal end of the first channel 96. The bend 98 may include two turns, for example, each turning 90 degrees, such that after the bend 98, the first channel 96 may extend substantially opposite to the first direction 80 toward a dead end 100 of the first channel 96. The distal sidewall of the bend 98 may be inclined relative to the first direction 80. Towards the dead end 100, the first channel 96 may include a hook-shaped portion 102 that is inclined relative to the first direction 80. The distal surface of the hook-shaped portion 102 can define a support surface. In the first state of the needle sleeve 46, the guide pin 90 can be arranged in the middle section of the first channel 96, offset distally from the dead end 100, and at the distal end of the inclined portion in the middle section of the first channel 96.

[0084] The torsion protection 92 of the needle sleeve 46 can be arranged within the second channel 104 and can be guided by the second channel 104 during movement of the needle sleeve 46 relative to the main rod 21. The second channel 104 can extend parallel to the first direction 80 and therefore parallel to the direction of movement of the needle sleeve 46 (i.e., the first direction (see...)). Figure 11 The torsion protection element 92 within the second channel 104 can be used as a protective element to prevent the second section 86 from rotating relative to the housing 22, particularly the main rod 21.

[0085] Figure 11 Demonstrated in the second state Figure 10 The needle sleeve 46 and the main rod 21. In the second state of the needle sleeve 46, the needle sleeve 46 has moved from its first position toward its second position. In other words, compared to the first state, in the second state, the needle sleeve 46 has moved partially relative to the main rod 21, for example, because the drug delivery device 20 is at least partially disposed on the user's skin.

[0086] The guide interface can be configured such that when the needle sleeve 46 moves in the first direction 80, the first segment 84 is moved in the second direction 82 via the guide interface. Specifically, in the second state of the needle sleeve 46, the needle sleeve 46 has already moved in the first direction 80, and the guide pin 90 is guided within the first channel 96, for example, along an inclined portion in the middle section of the first channel 96 toward the bend 98. As the guide pin 90 moves along the inclined portion of the first channel 96, the first segment 84 of the needle sleeve 46 can move relative to the second segment 86 perpendicular to the first direction 80 in the second direction 82, and the flexible connector (e.g., flexible rod 94) can be biased by flexure because the second segment 86 of the needle sleeve 46 can be fixed by a torsion guard 92 within the second channel 104 to prevent any rotation.

[0087] Figure 12 Demonstrates the third state Figure 10 The needle sleeve 46 and the main rod 21. In the third state of the needle sleeve 46, the needle sleeve 46 can be in its second position. In other words, in the third state, the needle sleeve 46 is moved as far as possible into the main rod 21, for example, because the drug delivery device 20 is pressed against the user's skin. Therefore, in the third state of the needle sleeve 46, the needle 27 is exposed by the needle sleeve 46. With the needle sleeve 46 in its second position, the guide pin 90 has reached the bend 98 of the first channel 96. Under the force of the biased flexible rod 94, the first section 84 can move in the opposite direction to the second direction 82, and the guide pin 90 can move within the bend 98. In other words, in the third state of the needle sleeve 46, the biased flexible rod 94 forces the guide pin 90 through the bend 98 in the opposite direction to the second direction 82.

[0088] Figure 13 Demonstrates the fourth state Figure 10 The needle sleeve 46 and the main rod 21. In the fourth state, the needle sleeve 46 can still be in its second position, and when the needle sleeve 46 is in its second position, the guide pin 90 can move along the bend 98 under the force of the slack in the flexible connector. In particular, in the fourth state of the needle sleeve 46, the flexible rod 94 can be relaxed, and the first segment 84 can remain stationary relative to the second segment 86. In other words, the first segment 84 and the second segment 86 can be in their initial relative rotational positions according to the first state.

[0089] Figure 14 Demonstrates the fifth state Figure 10The needle sleeve 46 and the main rod 21. In the fifth state, the needle sleeve 46 can move from its second position toward its third position. In the fifth state of the needle sleeve 46, the drug delivery device 20 may have been partially removed from the user's skin. The guide interface can be configured such that when the needle sleeve 46 moves from its second position to the third position in a direction opposite to the first direction 80, the first segment 84 is further moved in a direction opposite to the second direction 82 via the guide interface. In particular, the guide pin 90 can be forced past the hook portion 102 of the first channel 100, such that the first segment 84 rotates relative to the second segment 86, and the flexible coupling (e.g., the flexible rod 94) is biased again. The hook portion 102 can provide an engaging element (support surface) for the guide interface. When the drug delivery device 20 is removed from the user's skin, the needle sleeve 46 can be pushed out of the housing 22, for example by the needle sleeve spring 48, such that the guide pin 90 is forced past the hook portion 102 (see Figure 14 Then, when the needle sleeve 46 reaches its third position, the first section 84 rotates relative to the second section 86 in the second direction 82 due to the force of the biased flexible coupling, and the first section 84, in particular the guide pin 90, can engage with the engagement element (see...). Figure 15 This engagement locks the needle sleeve 46 in the third position, preventing movement toward the second position. The support surface may extend parallel to the second direction.

[0090] In an embodiment not shown, the support surface may be tilted relative to the first direction 80 and / or relative to the second direction 82. This tilt may be configured to limit the movement of the guide pin 90 opposite to the second direction 82 in order to counteract the reversal of the first segment 84, such as rotation opposite to the second direction 82.

[0091] Figure 15 Demonstrates the sixth state Figure 10 The needle sleeve 46 and the main shaft 21. In the sixth state, the needle sleeve 46 is in its third position. In the sixth state, the drug delivery device 20 may have been completely removed from the user's skin, and the needle sleeve 46 can completely cover the needle 27. The guide interface can be configured such that after the guide pin 90 passes the hook portion 102 and before the needle sleeve 46 reaches its third position, the first segment 84 can be moved in the second direction 82 by loosening the flexible coupling. The guide pin 90 can snap into the dead end 100 of the first channel 96, so that the needle sleeve 46 is securely engaged with the main shaft 21.

[0092] The terms “drug” or “pharmaceutical” are used synonymously herein and describe pharmaceutical preparations comprising one or more active pharmaceutical ingredients or pharmaceutically acceptable salts or solvates thereof, and optionally pharmaceutically acceptable carriers. In the broadest sense, an active pharmaceutical ingredient (“API”) is a chemical structure that has a biological effect on humans or animals. In pharmacology, a drug or pharmaceutical preparation is used to treat, cure, prevent, or diagnose a disease or to otherwise enhance physical or mental health. Drugs or pharmaceutical preparations may be used for a limited duration or periodically for chronic disorders.

[0093] As described below, a drug or pharmaceutical preparation may include at least one API or combination thereof in different types of pharmaceutical formulations for the treatment of one or more diseases. Examples of APIs may include small molecules (having a molecular weight of 500 Da or less); polypeptides, peptides, and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); carbohydrates and polysaccharides; and nucleic acids, double-stranded or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids (such as antisense DNA and RNA), small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids may be incorporated into molecular delivery systems (such as vectors, plasmids, or liposomes). Mixtures of one or more drugs are also considered.

[0094] Drugs or pharmaceutical preparations may be contained in primary packaging or "drug reservoirs" suitable for use with drug delivery devices. Drug reservoir 101a may be, for example, a cartridge, syringe, reservoir, or other robust or flexible vessel (bag) configured to provide a suitable chamber for storing (e.g., short-term or long-term storage) one or more drugs. For example, in some cases, the chamber may 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 may be designed to store the drug for about 1 month to about 2 years. Storage may be carried out at room temperature (e.g., about 20°C) or at refrigerated temperatures (e.g., about -4°C to about 4°C). In some cases, the drug reservoir may be or may include a dual-chamber cartridge configured to separately store two or more components (e.g., API and diluent, or two different drugs) of the pharmaceutical preparation to be administered, one component in each chamber. In such cases, the two chambers of the dual-chamber cartridge may be configured to allow mixing between the two or more components before and / or during administration to a human or animal. For example, the two chambers can be configured such that they are in fluid communication with each other (e.g., through a conduit between the two chambers), allowing the user to mix the two components as needed before dispensing. Alternatively or additionally, the two chambers can be configured to allow mixing during the dispensing of the components into a human or animal body.

[0095] The drugs or agents contained in the drug delivery devices described herein can be used to treat and / or prevent many different types of medical barriers. Examples of barriers include, for example, diabetes or diabetes-related complications (such as diabetic retinopathy), thromboembolic barriers (such as deep vein or pulmonary thromboembolism). Other examples of barriers are acute coronary syndrome (ACS), angina pectoris, myocardial infarction, tumors, macular degeneration, inflammation, hay fever, atherosclerosis, and / or rheumatoid arthritis. Examples of APIs and drugs are those described in the following manuals: such as Rote Liste 2014 (e.g., but not limited to main group 12 (antidiabetic drugs) or 86 (oncology drugs)) and Merck Index 15.

[0096] Examples of APIs used to treat and / or prevent type 1 or type 2 diabetes or complications associated with type 1 or type 2 diabetes include insulin (e.g., human insulin, or human insulin analogs or derivatives); glucagon-like peptide-1 (GLP-1), GLP-1 analogs or GLP-1 receptor agonists, or analogs or derivatives thereof; dipeptidyl peptidase-4 (DPP4) inhibitors, or pharmaceutically acceptable salts or solvates thereof; or any mixture of the above. As used herein, the terms “analyte” and “derivative” refer to a polypeptide having a molecular structure that is formally derived from the structure of a naturally occurring peptide (e.g., the structure of human insulin) by deletion and / or exchange of at least one amino acid residue present in a naturally occurring peptide and / or by addition of at least one amino acid residue. The added and / or exchanged amino acid residues may be encoding amino acid residues or other naturally occurring residues or purely synthetic amino acid residues. Insulin analogs are also referred to as “insulin receptor ligands”. Specifically, the term "derivative" refers to a polypeptide having a molecular structure that is formally derived from the structure of a naturally occurring peptide (e.g., human insulin), wherein one or more organic substituents (e.g., fatty acids) are bound to one or more amino acids. Optionally, one or more amino acids present in a naturally occurring peptide may have been missing and / or substituted with other amino acids (including non-coding amino acids), or amino acids (including non-coding amino acids) may have been added to a naturally occurring peptide.

[0097] Examples of insulin analogs are Gly(A21), Arg(B31), Arg(B32) human insulin (glargine insulin); Lys(B3), Glu(B29) human insulin (glutamate insulin); Lys(B28), Pro(B29) human insulin (lispro insulin); Asp(B28) human insulin (aspart 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.

[0098] Examples of insulin derivatives include, for instance, B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (detemir®); 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; and B30-N-myristoyl-ThrB29. LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-γ-glutamyl)-des(B30) human insulin, B29-N-ω-carboxypentadecanoyl-γ-L-glutamyl-des(B30) human insulin (Degludec insulin, Tresiba®); B29-N-(N-lithochyl-γ-glutamyl)-des(B30) human insulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin and B29-N-(ω-carboxyheptadecanoyl) human insulin.

[0099] Examples of GLP-1, GLP-1 analogs, and GLP-1 receptor agonists include, for example, lixilamide (Lyxumia®), exenatide (Exendin-4, Byetta®, Bydureon®, a 39-amino acid peptide produced by the salivary glands of the Gila monster), liraglutide (Victoza®), semaglutide, tasglutide, abiglutide (Syncria®), duraglutide (Trulicity®), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide / HM-11260C (efpeglenatide), HM-15211, CM-3, and GLP-1. Eligen, ORMD-0901, NN-9423, NN-9709, 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, ZP-DI-70, TT-401 (Pegapamodtide), BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Tepirotide (LY3298176), Bamadutide (SAR425899), Exenatide-XTEN, and Glucagon-Xten.

[0100] Examples of oligonucleotides include, for instance, mirtamicin sodium (Kynamro®), a cholesterol-reducing antisense agent used to treat familial hypercholesterolemia, or RG012 used to treat Alport syndrome.

[0101] Examples of DPP4 inhibitors are liraliptin, vedagliptin, sitagliptin, degliptin, saxagliptin, and berberine.

[0102] Examples of hormones include pituitary or hypothalamic hormones or regulatory active peptides and their antagonists, such as gonadotropins (follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotropin, fertility-stimulating hormone), growth hormone (growth hormone), desmopressin, terlipressin, gosorelin, triptorelin, leuprorelin, buserorelin, nafarelin, and goserelin.

[0103] Examples of polysaccharides include glucosamine, 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. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. An example of a hyaluronic acid derivative is Hylan GF 20 (Synvisc®), a sodium hyaluronate.

[0104] As used herein, the term "antibody" refers to an immunoglobulin molecule or its antigen-binding portion. Examples of antigen-binding portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments that retain the ability to bind antigens. Antibodies can be polyclonal antibodies, monoclonal antibodies, recombinant antibodies, chimeric antibodies, deimmunized or humanized antibodies, fully human antibodies, non-human (e.g., mouse) antibodies, or single-chain antibodies. In some embodiments, antibodies have effector functions and can immobilize complement. In some embodiments, the ability of an antibody to bind to an Fc receptor is reduced or absent. For example, an antibody can be an isotype or subtype, an antibody fragment, or a mutant that does not support binding to an Fc receptor, for example, its Fc receptor-binding region has been mutagenized or deleted. The term "antibody" also includes antigen-binding molecules based on tetravalent bispecific tandem immunoglobulins (TBTI) and / or dual variable-region antibody-like binding proteins with cross-binding region orientation (CODV).

[0105] 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 that does not contain the full-length antibody polypeptide but still contains at least a portion of the full-length antibody polypeptide capable of binding to an antigen. Antibody fragments may contain cleaved portions of the full-length antibody polypeptide, but the term is not limited to such cleaved fragments. Antibody fragments that can be used in this invention include, for example, Fab fragments, F(ab')2 fragments, scFv (single-chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments (e.g., bispecific, trispecific, tetraspecific, and multispecific antibodies (e.g., double-chain, triple-chain, and quadruple-chain antibodies)), monovalent or multivalent antibody fragments (e.g., bivalent, trivalent, quadruvalent, and multivalent antibodies), microantibodies, chelated recombinant antibodies, tri- or bivalent antibodies, intracellular antibodies, nanobodies, small modular immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camel-derived antibodies, and antibodies containing VHH. Further examples of antigen-binding antibody fragments are known in the art.

[0106] The term "complementarity-determining region" or "CDR" refers to a short polypeptide sequence within the variable region of both heavy and light chain polypeptides, primarily responsible for mediating specific antigen recognition. The term "frame region" refers to an amino acid sequence within the variable region of both heavy and light chain polypeptides; it is not a CDR sequence and is primarily responsible for maintaining the correct positioning of the CDR sequence to allow antigen binding. Although frame regions, as is known in the art, typically do not directly participate in antigen binding, certain residues within the frame region of some antibodies can directly participate in antigen binding or can affect the ability of one or more amino acids in the CDR to interact with the antigen.

[0107] Examples of antibodies are anti-PCSK-9 mAb (e.g., aliximumab), anti-IL-6 mAb (e.g., thalidomumab), and anti-IL-4 mAb (e.g., dupilumab).

[0108] Further examples of APIs used for the prevention of hemophilia A or B (with or without inhibitors) include siRNAs that target antithrombin. An example of an antithrombin-targeting siRNA is fexocilan. The terms “prevention” and “prophylactic treatment” are used interchangeably herein. It is also contemplated that a pharmaceutically acceptable salt of any API described herein be used in a drug or pharmaceutical preparation in a drug delivery device. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts.

[0109] Those skilled in the art will understand that modifications (additions and / or removals) can be made to the different components, pharmaceutical formulations, devices, methods, systems, and embodiments of the APIs described herein without departing from the full scope and spirit of the invention, which covers such modifications and any and all equivalents thereof.

[0110] Example drug delivery devices may involve needle-based injection systems, as described in Table 1 of Section 5.2 of ISO 11608-1:2014(E). As described in ISO 11608-1:2014(E), needle-based injection systems can be broadly categorized into multiple-dose container systems and single-dose (partially or completely emptied) container systems. The container may be a replaceable container or an integral, non-replaceable container.

[0111] As further described in ISO 11608-1:2014(E), a multiple-dose container system can relate to a needle-based injection device with replaceable containers. In such a system, each container holds multiple doses, the size of which can be fixed or variable (preset by the user). Another multiple-dose container system can relate to a needle-based injection device with an integrated, non-replaceable container. In such a system, each container holds multiple doses, the size of which can be fixed or variable (preset by the user).

[0112] As further described in ISO 11608-1:2014(E), a single-dose container system can relate to a needle-based injection device with a replaceable container. In one example of such a system, each container contains a single dose, in which the entire deliverable volume is discharged (completely emptied). In another example, each container contains a single dose, in which a portion of the deliverable volume is discharged (partially emptied). Also as described in ISO 11608-1:2014(E), a single-dose container system can relate to a needle-based injection device with an integrated, non-replaceable container. In one example of such a system, each container contains a single dose, in which the entire deliverable volume is discharged (completely emptied). In another example, each container contains a single dose, in which a portion of the deliverable volume is discharged (partially emptied).

[0113] Fetrazol as an API in the device

[0114] Fetuximab is a synthetic, chemically modified double-stranded small interfering RNA (siRNA) oligonucleotide that is covalently linked to a tri-antennae N-acetyl-galactosamine (GalNAc) ligand targeting AT3 mRNA in the liver, thereby inhibiting the synthesis of antithrombin. See, for example, Pasi et al., N Engl J Med. [New England Journal of Medicine] (2017) 377(9):819-28. The nucleosides in each strand of feetuximab are linked by 3'-5' phosphodiester or thiophosphate bonds, forming the sugar-phosphate backbone of the oligonucleotide.

[0115] The sense strand and antisense strand contain 21 and 23 nucleotides, respectively. The 3' end of the sense strand is conjugated to the GalNAc-containing moiety (referred to herein as L96) via a phosphodiester bond. The sense strand contains two consecutive phosphate thioester bonds at its 5' end. The antisense strand contains four phosphate thioester bonds, two at the 3' end and two at the 5' end. The 21 nucleotides of the sense strand are hybridized with the complementary 21 nucleotides of the antisense strand, thus forming 21 nucleotide base pairs and a two-base overhang at the 3' end of the antisense strand. See also U.S. Patents 9,127,274, 11,091,759, US2020 / 0163987 A1, and WO 2019 / 014187, the entire contents of which are expressly incorporated herein by reference.

[0116] The two nucleotide chains of non-fortuccinyl are shown below:

[0117] The semantic chain is: 5'Gf-ps-Gm-ps-Uf-Um-Af-Am-Cf-Am-Cf-Cf-Af-Um-Uf-Um-Af-Cm-Uf-Um-Cf-Am-Af-L96 3' (SEQ ID NO:1), and

[0118] Antisense strand: 5' Um-ps-Uf-ps-Gm-Af-Am-Gf-Um-Af-Am-Af-Um-Gm-Gm-Uf-Gm-Uf-Um-Af-Am-Cf-Cm-ps-Am-ps-Gm 3' (SEQ ID NO: 2),

[0119] in,

[0120] Af = 2'-deoxy-2'-fluoroadenosine

[0121] Cf = 2'-deoxy-2'-fluorocytidine

[0122] Gf = 2'-deoxy-2'-fluoroguanosine

[0123] Uf = 2'-deoxy-2'-fluorouridine

[0124] Am = 2'-O-methyladenosine

[0125] Cm = 2'-O-methylcytidine

[0126] Gm = 2'-O-methylguanosine

[0127] Um = 2'-O-methyluridine

[0128] "-" (hyphen) = 3'-5' phosphate diester-linked sodium salt

[0129] "-ps-" = 3'-5' thiophosphate-linked sodium salt

[0130] Furthermore, L96 has the following formula:

[0131] (I).

[0132] As used herein, the terms “2’-deoxy-2’-fluoroadenosine” and “2’-fluoroadenosine” are used interchangeably.

[0133] As used herein, the terms “2’-deoxy-2’-fluorocytidine” and “2’-fluorocytidine” are used interchangeably.

[0134] As used herein, the terms “2’-deoxy-2’-fluoroguanosine” and “2’-fluoroguanosine” are used interchangeably.

[0135] As used herein, the terms “2’-deoxy-2’-fluorouridine” and “2’-fluorouridine” are used interchangeably.

[0136] The expanded structural formula, molecular formula, and molecular weight of phenotype are shown in Figure 16.

[0137] The structure of non-tocopherol can also be described by the following diagram, where X is O:

[0138] .

[0139] Fetozilan is shown in Figure 16 as a sodium salt.

[0140] In some embodiments, the device delivers fexoxilan in an aqueous solution at a concentration of about 40 to about 200 mg / mL (e.g., about 50 to about 150 mg / mL, about 80 to about 110 mg / mL, or about 90 to about 110 mg / mL). Values ​​between these ranges and values ​​are also intended to be part of this disclosure as used herein. Additionally, ranges using any combination of these values ​​as upper and / or lower limits are intended to be included. In other embodiments, the pharmaceutical preparation comprises fexoxilan at a concentration of about 40, about 50, about 75, about 100, about 125, about 150, or about 200 mg / mL in an aqueous solution. In some embodiments, fexoxilan is provided at a concentration of about 100 mg / mL in an aqueous solution.

[0141] The term “delivery” is intended to mean “application”.

[0142] Unless specifically stated or otherwise readily apparent from the context, as used herein, the terms “approximately” or “about” refer to a value within an acceptable margin of error for a particular value as determined by a person of ordinary skill in the art, a range which will depend on how the measurement or determination is performed. For example, “approximately” or “about” may mean a range of up to 10% (i.e., ± 10%). Thus, “approximately” or “about” can be understood as greater than or less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, 0.01%, or 0.001%. When specific values ​​are provided in this disclosure, unless otherwise stated, the meaning of “approximately” or “about” should be assumed to be within an acceptable margin of error for that specific value.

[0143] While the dosage and weight of fexoxicam described herein refer to the weight of fexoxicam free acid (active fraction), administration of fexoxicam to a patient herein refers to administration of fexoxicam sodium (active pharmaceutical ingredient) in a pharmaceutically appropriate aqueous solution (e.g., phosphate-buffered saline at physiological pH). For example, approximately 100 mg / mL fexoxicam means approximately 100 mg of fexoxicam free acid per mL (equivalent to approximately 106 mg of fexoxicam sodium, active pharmaceutical ingredient). Unless otherwise stated, the fexoxicam weights listed in this disclosure are the weight of fexoxicam free acid (active fraction).

[0144] In some embodiments, the pharmaceutical preparation in the device comprises fexoline in phosphate-buffered saline. The phosphate concentration in the solution may be from about 1 to about 10 mM (e.g., about 2, about 3, about 4, about 5, about 6, about 7, about 8, or about 9 mM), and the pH may be about 6.0-8.0. The pharmaceutical preparation described herein may include stabilizers, such as EDTA. The pharmaceutical preparation may be preservative-free. In some embodiments, the fexoline pharmaceutical preparation in the device is preservative-free and contains about 100 mg of fexoline per mL of about 5 mM phosphate-buffered saline (PBS) solution, or is composed of or substantially composed of about 100 mg of fexoline. In some embodiments, the fexoline pharmaceutical preparation in the device is preservative-free and contains, consists of, or substantially consists of fexoline in about 5 mM phosphate-buffered saline (PBS) solution. The PBS solution consists of sodium chloride, disodium hydrogen phosphate (heptahydrate), and sodium dihydrogen phosphate (monohydrate). The pH of pharmaceutical preparations can be adjusted to approximately 7.0 or approximately 7.1 using sodium hydroxide solution and diluted phosphoric acid.

[0145] In some embodiments, the non-folic acid phosphate preparation in the device for subcutaneous delivery contains non-folic acid phosphate in a 5 mM phosphate-buffered saline solution at pH 7.0, the phosphate-buffered saline solution having 0.64 mM NaH₂PO₄, 4.36 mM Na₂HPO₄, and 84 mM NaCl. In some embodiments, the pharmaceutical preparations for the non-folic acid phosphate phosphate solution for subcutaneous delivery are shown in Table 1 below:

[0146] Table 1. Exemplary non-toxican pharmaceutical preparations

[0147]

[0148] Appropriate amount: Appropriate amount

[0149] In some embodiments, pharmaceutical formulations for subcutaneous delivery of non-tuzelan solutions using a device may be described, as shown in Table 2 below.

[0150] Table 2. Exemplary non-toxican pharmaceutical preparations

[0151]

[0152] In some embodiments, the device can be used to deliver a single dose of fetoxil, wherein the single dose comprises about 20 mg to about 80 mg of fetoxil (e.g., about 20 mg, about 25 mg, about 30 mg, about 40 mg, about 50 mg, or about 80 mg). In some embodiments, the device can be used to deliver a single dose of fetoxil, wherein the single dose comprises about 1 mg to about 30 mg of fetoxil (e.g., about 1.25 mg, about 2.5 mg, about 5 mg, about 10 mg, about 20 mg, or about 30 mg).

[0153] In one embodiment, the device can be used to deliver a single dose of about 80 mg of fetacycline. In one embodiment, the device can be used to deliver a single dose of about 50 mg of fetacycline. In one embodiment, the device can be used to deliver a single dose of about 20 mg of fetacycline. In one embodiment, the device can be used to deliver a single dose of about 30 mg of fetacycline. In one embodiment, the device can be used to deliver a single dose of about 10 mg of fetacycline. In one embodiment, the device can be used to deliver a single dose of about 5 mg of fetacycline. In one embodiment, the device can be used to deliver a single dose of about 2.5 mg of fetacycline. In one embodiment, the device can be used to deliver a single dose of about 1.25 mg of fetacycline.

[0154] In some embodiments, a single dose of fexocylan can be delivered in a delivery volume of about 0.5 mL to about 1 mL (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL). Other delivery volumes described herein may also be used.

[0155] In one embodiment, the device can be used to deliver a single dose of about 80 mg of fetacidin (about 100 mg fetacidin / mL) in about 0.8 mL. In one embodiment, the device can be used to deliver a single dose of about 50 mg of fetacidin (about 100 mg fetacidin / mL) in about 0.5 mL. In one embodiment, the device can be used to deliver a single dose of about 20 mg of fetacidin (about 40 mg fetacidin / mL) in about 0.5 mL. In one embodiment, the device can be used to deliver a single dose of about 30 mg of fetacidin (about 60 mg fetacidin / mL) in about 0.5 mL. In one embodiment, the device can be used to deliver a single dose of about 10 mg of fetacidin (about 20 mg fetacidin / mL) in about 0.5 mL. In one embodiment, the device can be used to deliver a single dose of about 5 mg of fetacidin (about 10 mg fetacidin / mL) in about 0.5 mL. In one embodiment, the device can be used to deliver a single dose of about 2.5 mg fetocilan (about 5 mg fetocilan / mL) in about 0.5 mL. In another embodiment, the device can be used to deliver a single dose of about 1.25 mg fetocilan (about 2.5 mg fetocilan / mL) in about 0.5 mL.

[0156] In one embodiment, the device delivers a preventatively effective dose of non-tuximab for preventative treatment of hemophilia in patients in need (e.g., hemophilia A or B patients with or without inhibitors). A “preventatively effective dose” refers to the amount of non-tuximab that helps patients with hemophilia A or B (with or without inhibitors) achieve desired clinical endpoints, such as a reduction in annualized bleeding rate (ABR), annualized joint bleeding rate (AjBR), annualized spontaneous bleeding rate (AsBR), or frequency of bleeding episodes. As used herein, in the context of non-tuximab, the term “treat / treating / treatment” includes preventative treatment of the disease and refers to achieving desired clinical endpoints.

[0157] Patients with hemophilia A or B who have inhibitors are those who have developed alloantibodies against a previously received factor (e.g., factor VIII for hemophilia A or factor IX for hemophilia B). Patients with hemophilia A or B who have inhibitors may have difficulty being treated with alternative clotting factor therapy. Patients without inhibitors are those who do not have such alloantibodies. This treatment approach may be beneficial for both hemophilia A and hemophilia B patients with inhibitors.

[0158] As used herein, a patient with "hemophilia A or B (with or without inhibitors)" may refer to 1) a hemophilia A patient with inhibitors, or 2) a hemophilia B patient with inhibitors, 3) a hemophilia A patient without inhibitors, or 4) a hemophilia B patient without inhibitors. As used herein, "patient" refers to a human patient. "Patient" may also refer to a human subject.

[0159] In some embodiments, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) with a subcutaneous dose of about 50 mg of fenostroside every two months (or every eight weeks). In other embodiments, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) with a subcutaneous dose of about 50 mg of fenostroside every month (or every four weeks). In still other embodiments, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) with a subcutaneous dose of about 80 mg of fenostroside every two months (or every eight weeks). In still other embodiments, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) with a subcutaneous dose of about 80 mg of fenostroside every month (or every four weeks). In still other embodiments, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) with a subcutaneous dose of about 20 mg of fenostroside every two months (or every eight weeks). In yet another embodiment, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) at a subcutaneous dose of approximately 20 mg of fenestrated lanolin per month (or every four weeks). In yet another embodiment, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) at a subcutaneous dose of approximately 10 mg of fenestrated lanolin per month (or every four weeks). In yet another embodiment, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) at a subcutaneous dose of approximately 30 mg of fenestrated lanolin per month (or every four weeks). In yet another embodiment, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) at a subcutaneous dose of approximately 5 mg of fenestrated lanolin per month (or every four weeks). In yet another embodiment, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) at a subcutaneous dose of approximately 2.5 mg of fenestrated lanolin per month (or every four weeks). In yet another embodiment, the device can be used for prophylactic treatment of patients with hemophilia A or B (with or without inhibitors) with a subcutaneous dose of approximately 1.25 mg of fexocylan per month (or every four weeks).

[0160] Accordingly, this article provides a method for prophylactic treatment of patients with hemophilia A or hemophilia B (with or without inhibitors), comprising subcutaneously delivering a prophylactic dose of fetoxiclan to a patient in need using the device. The prophylactic dose of fetoxiclan can be any dose provided herein, such as about 1 mg to about 80 mg, about 1 mg to about 30 mg, or about 20 mg to about 80 mg. The prophylactic dose of fetoxiclan can be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactic dose of fetoxiclan can be delivered monthly (or every four weeks) or every two months (or every eight weeks). Fetoxiclan can be delivered in delivery volumes of about 0.5 mL to about 1 mL (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

[0161] As an example, prophylactic treatment for patients with hemophilia A or hemophilia B (with or without inhibitors) may include subcutaneous delivery of approximately 50 mg of fexoside to the patient in need once a month (or every four weeks) or every two months (or every eight weeks) using this device. Approximately 50 mg of fexoside can be delivered in approximately 0.5 mL of PBS (concentration approximately 100 mg fexoside / mL).

[0162] Furthermore, this article provides a method for reducing the frequency of bleeding episodes in patients with hemophilia A or B (with or without inhibitors), comprising subcutaneously delivering a prophylactic dose of fetoxiclan to a patient in need using the device. The prophylactic dose of fetoxiclan can be any dose provided herein, such as about 1 mg to about 80 mg, about 1 mg to about 30 mg, or about 20 mg to about 80 mg. The prophylactic dose of fetoxiclan can be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactic dose of fetoxiclan can be delivered monthly (or every four weeks) or every two months (or every eight weeks). Fetoxiclan can be delivered in delivery volumes of about 0.5 mL to about 1 mL (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

[0163] As an example, a method to reduce the frequency of bleeding episodes in patients with hemophilia A or B (with or without inhibitors) may include subcutaneously delivering approximately 50 mg of fexoside to the patient in need once a month (or every four weeks) or every two months (or every eight weeks) using this device. Approximately 50 mg of fexoside can be delivered in approximately 0.5 mL of PBS (concentration approximately 100 mg fexoside / mL).

[0164] Furthermore, this article provides a method for reducing the acute bleeding rate (ABR) in patients with hemophilia A or B (with or without inhibitors), comprising subcutaneously delivering a prophylactic dose of fetoxiclan to a patient in need using the device. The prophylactic dose of fetoxiclan can be any dose provided herein, such as about 1 mg to about 80 mg, about 1 mg to about 30 mg, or about 20 mg to about 80 mg. The prophylactic dose of fetoxiclan can be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactic dose of fetoxiclan can be delivered monthly (or every four weeks) or every two months (or every eight weeks). Fetoxiclan can be delivered in delivery volumes of about 0.5 mL to about 1 mL (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

[0165] As an example, a method for reducing ABR in patients with hemophilia A or B (with or without inhibitors) may include subcutaneously delivering approximately 50 mg of fexoside to the patient in need once a month (or every four weeks) or every two months (or every eight weeks) using this device. Approximately 50 mg of fexoside can be delivered in approximately 0.5 mL of PBS (concentration approximately 100 mg fexoside / mL).

[0166] Furthermore, this article provides a method for reducing AjBR in patients with hemophilia A or B (with or without inhibitors), comprising subcutaneously delivering a prophylactic dose of fetoxiclan to a patient in need using the device. The prophylactic dose of fetoxiclan can be any dose provided herein, such as about 1 mg to about 80 mg, about 1 mg to about 30 mg, or about 20 mg to about 80 mg. The prophylactic dose of fetoxiclan can be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactic dose of fetoxiclan can be delivered monthly (or every four weeks) or every two months (or every eight weeks). Fetoxiclan can be delivered in delivery volumes of about 0.5 mL to about 1 mL (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

[0167] As an example, a method for reducing AjBR in patients with hemophilia A or B (with or without inhibitors) may include subcutaneously delivering approximately 50 mg of fexoside to the patient in need once a month (or every four weeks) or every two months (or every eight weeks) using this device. Approximately 50 mg of fexoside can be delivered in approximately 0.5 mL of PBS (concentration approximately 100 mg fexoside / mL).

[0168] Furthermore, this article provides a method for reducing AsBR in patients with hemophilia A or B (with or without inhibitors), comprising subcutaneously delivering a prophylactic dose of fetoxiclan to a patient in need using the device. The prophylactic dose of fetoxiclan can be any dose provided herein, such as about 1 mg to about 80 mg, about 1 mg to about 30 mg, or about 20 mg to about 80 mg. The prophylactic dose of fetoxiclan can be, for example, about 1.25 mg, about 2.5 mg, about 5 mg, about 25 mg, about 30 mg, about 50 mg, or about 80 mg. The prophylactic dose of fetoxiclan can be delivered monthly (or every four weeks) or every two months (or every eight weeks). Fetoxiclan can be delivered in delivery volumes of about 0.5 mL to about 1 mL (e.g., about 0.5 mL, about 0.6 mL, about 0.7 mL, about 0.8 mL, about 0.9 mL, or about 1 mL).

[0169] As an example, a method for reducing AsBR in patients with hemophilia A or B (with or without inhibitors) may include subcutaneously delivering approximately 50 mg of fetoxil to the patient in need once a month (or every four weeks) or every two months (or every eight weeks) using this device. Approximately 50 mg of fetoxil can be delivered in approximately 0.5 mL of PBS (concentration approximately 100 mg fetoxil / mL).

[0170] Any invention described herein is not limited to the description in conjunction with exemplary embodiments. Rather, the invention and the associated disclosures include any new features and any combination of features, particularly any combination of features in the patent claims, even if the features or combinations are not expressly stated in the patent claims or exemplary embodiments.

[0171] Figure Labels

[0172] 20 drug delivery devices

[0173] 21 main rod

[0174] 22 shell

[0175] 23 hats

[0176] 24 medicine containers

[0177] 25 container ports

[0178] 25.1 Surface facing the near side

[0179] 26 chambers

[0180] 27 needles

[0181] 28 distribution terminals

[0182] 30 far end

[0183] 32 plugs

[0184] 34 bearing

[0185] 35 plunger rod arrangement

[0186] 36 ball head

[0187] 37 Part 1

[0188] 38 Part Two

[0189] 39 drive components

[0190] 40 allocation direction

[0191] 42 Energy Storage Components

[0192] 44 retainer

[0193] 45 axis

[0194] 46 needle sleeve

[0195] 48 needle sleeve spring

[0196] 50 needle shield

[0197] 52 Joining device

[0198] 54 engagement recess

[0199] 56 Release Components

[0200] 58 Grab Ring

[0201] 59 rings

[0202] 60 hooks

[0203] 62 stable cone

[0204] 64 finger grooves

[0205] 66 hands

[0206] 80 First Direction

[0207] 82 Second Direction

[0208] 84 Section 1

[0209] 86 Second Section

[0210] 88 through concave part

[0211] 90 Guide Sales

[0212] 92 Torsion Protection Component

[0213] 94 flexible rod

[0214] 96 First Channel

[0215] 98 bends

[0216] 100 Dead Ends

[0217] 102 Hook-shaped part

[0218] 104 Second Channel.

Claims

1. A drug delivery device (20), comprising: a housing (22) for receiving a drug container (24); a needle sleeve (46) configured to be movable relative to the housing (22) in a first direction (80) from a first position to a second position; wherein the needle sleeve (46) comprises a first section (84) and a second section (86), the first section (84) is configured for moving relative to the second section (86) in a second direction (82) perpendicular to the first direction (80) when the needle sleeve (46) is moved from the first position to the second position.

2. The drug delivery device (20) of claim 1, wherein the first and second sections (86) are flexibly coupled to each other by a flexible coupling, and are configured such that the first section (84) rotates and the second section (86) is fixed against rotation when the needle sleeve (46) is moved from the first position to the second position.

3. The drug delivery device (20) of claim 2, wherein the flexible coupling comprises at least one flexible rod (94), and the flexible rod (94) is configured for being biased when the first section (84) moves relative to the second section (86) in the second direction (82) or vice versa.

4. The drug delivery device (20) of claim 3, comprising at least two of said flexible rods (94), wherein the flexible rods (94) are separated from each other by a through recess (88) within the needle sleeve (46).

5. The drug delivery device (20) of any of the preceding claims, wherein the needle sleeve (46) is made in one piece.

6. The drug delivery device (20) of any of the preceding claims, wherein the first section (84) is coupled to the housing (22) by a guiding interface, and the guiding interface is configured such that the first section (84) is moved in the second direction (82) by the guiding interface when the needle sleeve (46) is moved in the first direction (80).

7. The drug delivery device (20) of claim 6, wherein the guiding interface is configured such that the first section (84) is moved in a direction opposite to the second direction (82) by the flexible coupling relaxing when the needle sleeve (46) is in its second position.

8. The drug delivery device (20) of claim 7, wherein the guiding interface is configured such that the first section (84) is further moved in a direction opposite to the second direction (82) by the guiding interface when the needle sleeve (46) is moved from its second position to a third position of the needle sleeve (46) in a direction opposite to the first direction (80).

9. The drug delivery device (20) of claim 8, wherein the guiding interface is configured such that the first section (84) is moved in the second direction (82) by the flexible coupling relaxing before the needle sleeve (46) reaches its third position.

10. The drug delivery device (20) of any one of claims 6 to 9, wherein the guiding interface comprises an engagement element, and the first section (84) is configured to engage with the engagement element when the needle sleeve (46) reaches the third position such that the needle sleeve (46) is locked in the third position against movement towards the second position.

11. The drug delivery device (20) of any one of claims 6 to 10, wherein the guiding interface comprises or consists of a guiding element and a guide for guiding the guiding element.

12. The drug delivery device (20) of one of the preceding claims, comprising a second channel (104) within the housing (22), the second channel (104) extending only in the first direction (80), wherein the second section (86) comprises a twist protection (92), and the twist protection (92) and the second channel (104) are configured to interact such that movement of the second section in the second direction or vice versa is limited.

13. The drug delivery device (20) of claim 12, wherein, the twist protection (92) moves within the second channel (104) in the first direction (80) when the needle sleeve (46) is moved in the first direction (80), thereby fixing the second section (86) against movement in the second direction (82).

14. The drug delivery device (20) of any one of the preceding claims, comprising an injection member for injecting a drug into an injection site.

15. The drug delivery device (20) of any one of the preceding claims, comprising a needle sleeve spring (48) coupled or couplable to the needle sleeve (46) and configured for moving the needle sleeve (46) in a direction opposite to the first direction (80) when the drug delivery device (20) is removed from the injection site.

16. The drug delivery device (20) of any one of the preceding claims, comprising the drug container (24) within the housing (22); and a drug within the drug container (24).

17. The drug delivery device (20) of claim 2 or any one of claims 3 to 15 when dependent on claim 2, wherein the first position is an initial position of the drug delivery device (20) and the second position is an operating position of the drug delivery device.

18. The drug delivery device (20) of any of the preceding claims, wherein, the first direction (80) is an axial direction of the drug delivery device (20) and wherein the second direction (82) is a circumferential direction of the drug delivery device (20).

19. The drug delivery device (20) of any of the preceding claims, wherein, the first section (84) has a closed circumference.

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