Drug delivery device and method for disconnecting drug administration element from at least portion of drug delivery device

Abstract

A drug delivery device (100) comprising a housing (102) for receiving a drug reservoir (101a) and comprising at least one support member is disclosed. The drug administration element (110) may be fluidly coupled to or may be fluidly coupleable to the drug reservoir (101a). The drug administration element (110) may define a drug outlet of the drug delivery device (100). The at least one support member may or may be coupleable to the drug administration element (110) to support the drug administration element (110) relative to the housing (102). The at least one support member may be configured to allow radial displacement of the housing (102) relative to the drug administration element (110) during a drug delivery operation.

Description

[0001] This disclosure relates to a drug delivery device. The drug delivery device can be an autoinjector or a manually or semi-automatically operated device. An energy storage element can be used in both autoinjectors and semi-automatically operated devices to transmit driving force for the injection operation. The energy storage element can be biased at the factory or by the user before use.

[0002] Medications may include insulin or GLP-1 (glucagon-like peptide). However, other medications may also be injected.

[0003] Self-administration is a significant advantage of these devices, as no medical personnel intervention is required. However, some patients may have reduced dexterity, such as due to tremors or decreased dexterity in their fingers, or they may be in a hurry, have difficulty concentrating, etc. Therefore, needle insertion and / or injection, as well as needle removal, may cause unnecessary pain.

[0004] The same problem may also be associated with other insertion and / or injection devices (such as lancets, syringes, pre-filled syringes, etc.).

[0005] The purpose of this disclosure is to provide an improved drug delivery device. This device should preferably be easy and / or comfortable to use, and / or include as few parts as possible. Furthermore, preferably, causes of pain should be reduced, for example, minimized. In addition, a corresponding method should also be provided.

[0006] This objective is achieved by the drug delivery device according to claim 1. Further embodiments are given in the dependent claims. The subject matter of the other independent claims may also achieve this objective.

[0007] According to an embodiment, a drug delivery device may include:

[0008] - A housing for receiving and / or for holding a drug reservoir, and / or

[0009] - At least one supporting member.

[0010] According to another embodiment, the drug delivery device can be an autoinjector, particularly a FLAI (Fast and / or Large Autoinjector). Large can mean an injection volume ranging from 2 ml to 10 ml, or from 2 ml to 5 ml, or from 2 ml to 3 ml. Fast can mean injecting a large volume of drug even within a range of 5 s to 20 s, for example, less than 20 s for a volume of 3 ml or for a volume ranging from 2 ml to 3 ml, or less than 30 s for a volume ranging from 5 ml or for a volume ranging from 3 ml to 5 ml. The viscosity of the drug can range from 1 cp to 50 cp (centipoise), for example, from 3 cp to 50 cp or from 15 cp to 30 cp. The diameter of the drug application element (e.g., the needle) can range from about size 25 to about size 31. Common sizes are size 27 and 29. However, size 25 can be used for fast and large autoinjectors. Larger volumes of medication can be used, such as medications for autoimmune diseases, especially those containing antibodies (e.g., monoclonal antibodies).

[0011] According to an embodiment, the housing may include an outer surface not surrounded by other parts of the drug delivery device. This outer surface may be a gripping surface that is gripped by a user or patient during use of the drug delivery device, such as during the injection of a drug into the body of a patient or animal.

[0012] According to an embodiment, the drug delivery device may have a longitudinal axis. The housing may extend along the longitudinal axis. The housing may include a proximal end and a distal end. The distal end may be closer to the needle of the drug delivery device than the proximal end. The housing may include only one portion or several portions, such as a main portion, such as an elongated cylindrical body, and preferably includes a rear housing portion that closes the main portion of the housing from the rear side of the housing (e.g., at the proximal end of the housing).

[0013] According to embodiments, the drug application element may be fluidly coupled to or fluidly coupled to a drug reservoir. The drug application element may define or may form a drug outlet of a drug delivery device. A typical example of a drug application element is a needle. The drug reservoir may be a container, such as a cartridge, syringe, plastic bag, or other fluid storage portion having a distal septum that can be pierced by a needle.

[0014] According to an embodiment, the at least one support member may be mechanically coupled to, or may be coupled to, the drug application element to support the drug application element relative to the housing. The support member and the drug application element may be mechanically coupled indirectly, for example, only via the drug reservoir or via at least one additional part of the drug reservoir and the drug delivery device. Alternatively, the support member and the drug application element may be directly coupled.

[0015] According to an embodiment, the at least one support member can be configured to allow radial displacement, such as radial displacement of the housing relative to the drug application element during a drug delivery operation. Therefore, the drug application element (e.g., a needle) can be disconnected from the housing or other parts of the drug delivery device, or the drug application element can be mechanically disconnected from another part of the housing or drug delivery device. The disconnection can be radial, and this disconnection preferably prevents radial movement of the housing from being transmitted to the drug reservoir and / or the drug application element (e.g., the needle) during insertion of the needle or other drug application element and / or during injection of the drug contained in the drug reservoir and / or during retraction of the needle or other drug application element and / or during other operations of the drug delivery device. Conversely, movement (e.g., radial movement of the needle or other drug application element) cannot be transmitted to other parts of the housing or drug delivery device, such as to the drug reservoir. This disconnection can reduce pain during injection and / or allow for precise injection, for example, with respect to injection depth and / or injection angle.

[0016] The relative radial displacement and / or movement of the drug application element and / or drug reservoir, such as the relative radial displacement and / or movement of the longitudinal axis of the drug application element and / or drug reservoir, may be parallel to the longitudinal axis of the drug delivery device and parallel to the housing.

[0017] Alternatively, this disconnection can allow the longitudinal axis of the drug delivery element and / or drug reservoir to pivot relative to the longitudinal axis of the housing and / or the longitudinal axis of other parts of the drug delivery device. The pivot angle between these two axes can be in the range of 1 to 5 degrees, or 1 to 3 degrees, or at least one, two, or three degrees. Angles greater than 3 degrees can be achieved with variations in the geometry of the associated parts. This angle can be less than 20 degrees, less than 10 degrees, or less than 6 degrees.

[0018] The at least one support member may include:

[0019] - Radial support members, such as soft materials, radially retaining portions (arms), and / or hinged arms (e.g., radially extending arms, or arms that extend radially and axially, e.g., proximally), and / or

[0020] - Axial support members, such as support arms extending parallel to or along the plunger, and / or

[0021] - Other types of support components.

[0022] Radial support members can radially support the drug reservoir and / or drug delivery element relative to the housing. Axial support members can axially support the drug reservoir and / or drug delivery element relative to the housing. Other types of support members can support the drug reservoir and / or drug delivery element both radially and axially. Details of embodiments of the support members are described below.

[0023] A radial support member can provide holding space for at least one drug reservoir within the housing. The radial support member may include at least one of at least a soft material portion for securing the drug reservoir and / or at least one flexible holding portion for securing the drug reservoir. This at least one of the soft material portion and / or the at least one flexible holding portion may allow at least a portion of the drug reservoir relative to the housing, or allow the entire drug reservoir to shift radially relative to the housing, during use of the drug delivery device. Since the drug reservoir can be mechanically coupled to a drug delivery element (e.g., a needle) in a rigid manner, the drug delivery element can also be radially disconnected from the housing, for example.

[0024] The relative radial displacement of the drug application element and / or drug reservoir (e.g., needle) relative to the housing may be at least 0.5 mm, at least 1 mm, at least 1.5 mm, at least 2 mm, or at least 3 mm, and / or may alternatively or additionally be less than 10 mm or less than 5 mm. With variations in the geometry of the associated parts, radial displacements exceeding 3 mm are possible.

[0025] Relative pivoting movement may exist between the drug delivery element / reservoir and the housing, for example, in the range of 1 to 5 degrees or in the range of 1 to 3 degrees, as described above. Pivoting may occur around a holding point / region in the proximal half, proximal third, or proximal quarter of the drug reservoir. Exemplarily, the syringe may have a needle length of 7.5 mm. The pivot point (fulcrum) may be 50 mm away from the needle exit, for example, a radius. Thus, the circumference of the circle is Pi (3.14) multiplied by, for example, a radius of 50 mm, resulting in, for example, 157 mm. In a given example, a pivot of 1 degree corresponds to a displacement of approximately 0.44 mm, a pivot of 2 degrees corresponds to a displacement of approximately 0.88 mm, and a pivot of approximately 3 degrees corresponds to a displacement of approximately 1.3 mm, and so on.

[0026] Before use, such as during transport of the drug delivery device, the drug reservoir may not be present in the holding space and / or the drug delivery device. Therefore, the user must, for example, insert or assemble the drug reservoir into or onto the drug delivery device shortly before injection, such as less than an hour before the drug is injected into the patient.

[0027] Alternatively, the drug reservoir can be assembled into the drug delivery device during factory production. Therefore, the use of the drug delivery device can be simplified.

[0028] According to an embodiment, the at least one support member may include a radial support member configured to radially support the drug reservoir during injection of the drug contained therein.

[0029] According to another embodiment, the radial support member may support the drug reservoir only at a portion of the drug reservoir whose axial length is at most three-quarters, at most two-thirds, at most half, or at most one-third of the axial length of the drug reservoir (preferably, the length of the cylindrical main body portion of the drug reservoir or the total length of the glass body of the drug reservoir).

[0030] According to another embodiment, the radial support member can support the proximal portion of the drug reservoir or can be configured to support the drug reservoir.

[0031] According to an embodiment, the radial support member may permanently support the drug application element and / or drug reservoir, for example, during storage of the drug delivery device and / or during injection and at least during injection and / or retraction.

[0032] The radial support member may include a soft material or a material with varying hardness. The soft material may be included within at least a portion of the soft material. The soft material may have a Shore A hardness below 90, 85, 80, 75, 70, 65, 60, 55, or below 50. The Shore A hardness may be greater than 5, greater than 10, greater than 15, greater than 20, or greater than 30. The Shore A hardness may be less than 90 (e.g., silicone, rubber), less than 85 (e.g., silicone, rubber), less than 75 (e.g., silicone, rubber), less than 70 (e.g., silicone), less than 65 (e.g., silicone), less than 60 (e.g., silicone), less than 55 (silicone), less than 50 (e.g., silicone), less than 40, or less than 35. Other materials, such as foam, rubber, etc., may also be used. Gels, such as gels contained in plastic bags or other suitable flexible bags, may also be used. The gel may have a Shore A hardness in the range of, for example, 45 to 98.

[0033] The Shore hardness measurement method was developed in 1915 by Albert Shore Corporation in the United States. Shore hardness is a material property of elastomers and plastics, and is defined in standards such as DIN (German Industrial Standard), EN (European Standard), ISO (International Organization for Standardization) 868, DIN ISO 7619-1, and ASTM (originally the American Society for Testing and Materials, now an international organization) D2240-00.

[0034] Shore A hardness measurement can be performed on soft elastomers, for example, using a needle with a blunt end. A Shore hardness tester can be used to measure Shore A hardness. The front surface of the truncated cone can have a diameter of 0.79 mm. The angle of the truncated cone can be 35 degrees. A weight of 1 kg can be used to press the needle into the soft material. The holding time can be 15 seconds. A penetration depth of 2.54 mm (0.1 inch) or greater corresponds to a Shore A hardness of zero. If the penetration depth is 0 mm, the hardness corresponds to 100 Shore A. Several scales are defined and can be used for measurement if appropriate.

[0035] Shore D hardness can also be used for elastomers, such as rigid or tough elastomers. The measuring needle can have a spherical or hemispherical end with a diameter of 0.2 mm. The needle can be narrowed at a 30-degree angle. A weight of 5 kg can be used to press the needle into the material. The holding time can again be 15 seconds.

[0036] Therefore, Shore A value 30 can correspond to Shore D value 6, Shore A value 55 can correspond to Shore D value 14, and Shore A value 75 can correspond to Shore D value 25, etc.

[0037] Other methods for determining hardness can also be used, such as the International Rubber Hardness Standard, which is known as microhardness in Germany, for example.

[0038] The soft material may extend from the inner wall of the housing to the holding space, or, if the drug reservoir is assembled within the holding space, to the drug reservoir. Alternatively, an inner housing may be used, which may be disposed between the inner surface of the housing and the holding space and / or the drug reservoir (if it is assembled within the holding space). The soft material and / or the inner housing may extend angularly upward along the entire circumference or at least half of the circumference. Several segments of soft material may be present, for example, with equal angular distances between two adjacent segments.

[0039] Only a portion of a soft material, such as a single tubular section, can be used at a suitable axial location in the drug delivery device. Alternatively, two or more portions of soft material can be used, arranged along the longitudinal axis of the drug delivery device with an axial distance greater than 0 mm or greater than 1 mm between adjacent portions. The distance between these portions of the soft material can be in the range of 5 mm to 30 mm or 10 mm to 50 mm, or it can have another suitable value. Therefore, a less soft material can be used.

[0040] Soft materials are particularly suitable for disconnecting drug delivery elements from the housing. Furthermore, soft materials can also provide some axial support, for example, if the friction between the drug reservoir and the soft material has a large or appropriate value.

[0041] According to an embodiment, the soft material, or at least a portion thereof, may include or may have a tubular shape. The inner lumen portion of the tube may be surrounded by the tube wall. The inner lumen portion may extend from the proximal end to the distal end of the tube. The inner lumen portion of the tube may form a holding space for retaining a drug reservoir. Therefore, the soft material has a simple shape and can be easily manufactured.

[0042] According to an alternative embodiment, the radial support member may include at least one flexible holding portion. This flexible holding portion may include at least one flexible element. The flexibility of the flexible element may be selected such that the at least one flexible element can be bent by radial forces during use of the drug delivery device. The flexible element may be or may include an elongated arm, beam, or sheet, etc.

[0043] Only one flexible retaining portion may be used at a suitable axial position on the longitudinal axis of the drug delivery device. Alternatively, two or more flexible retaining portions may be used, arranged along the longitudinal axis of the drug delivery device such that the axial distance between adjacent flexible retaining portions is greater than 0 mm or greater than 1 mm. This distance may be in the range of 5 mm to 30 mm or in the range of 10 mm to 50 mm, or may have another suitable value.

[0044] According to an embodiment, the flexible retaining portion may include at least one straight element extending radially inward to a retaining space for the drug reservoir. Therefore, a straight arm that can be easily manufactured can be used, for example, by injection molding. An elongated arm, such as one having a circular or elliptical cross-section, is preferred; a straight arm is also desirable.

[0045] Alternatively, the flexible holding portion may include a helical winding element. The helix of the helical winding portion may be parallel to or correspond to the longitudinal axis of the drug delivery device. The helical holding portion may be formed as a wound arm or a wound sheet. The helical wound arm may have a circular or elliptical cross-section.

[0046] According to an embodiment, the at least one support member may include at least one pre-injection support member. The at least one pre-injection support member may be configured to be in a first state before the drug application element is inserted into the patient's tissue (e.g., into the skin). The at least one pre-injection support member may be configured to be in a second state when the drug application element is inserted into the patient's tissue. In the first state, the pre-injection support member may, for example, support the drug application element and / or the drug reservoir radially, radially only, or radially and / or axially. In the second state, the pre-injection support member may not support the drug application element, or may support the drug application element to a lesser extent compared to the support in the first state; for example, the radial support force may be reduced by at least 50% compared to the holding force in the first state. The pre-injection support member may be moved back to the first state after injection or may be allowed to move back to the first state. Alternatively, the pre-injection support member may remain in the second state after injection.

[0047] Pre-injection support components may include flexible arms, electronically movable arms, articulated arms, telescopic arms, etc.

[0048] During the injection phase, the axially movable needle cap can disconnect the injection forearm or stabilizing arm from the drug reservoir and / or drug application element (e.g., from the syringe), thereby disconnecting the syringe or other element from the radial movement of the body or housing, or conversely, thereby disconnecting the housing from the radial movement of the syringe or another drug container.

[0049] Pre-injection support members can be used alone or in combination with other radial support members (such as soft materials and / or flexible retaining parts).

[0050] According to another embodiment, the drug delivery device may include at least one needle cap that is axially movable along a longitudinal axis from a first position to a second position proximal to the first position. In the first position, the needle cap covers or can be configured to cover a needle disposed on or potentially disposed on a drug reservoir. In its second position, the needle may be exposed or can be configured to be exposed. The housing may include at least one stabilizing arm forming a pre-injection support member, the at least one stabilizing arm being configured to stabilize the radial and / or axial position of the drug reservoir before the needle disposed on or potentially disposed on the drug reservoir is inserted into the patient's skin and / or tissue. The at least one stabilizing arm may extend from the housing or from another portion of the drug delivery device toward and through the drug reservoir. The at least one stabilizing arm may be positioned along the path of the needle cap during the movement of the needle cap from the first position to the second position. Therefore, the at least one stabilizing arm may be removed by the needle cap during the movement of the needle cap from the first position to the second position. The needle cap may include at least one arm, such as a long arm, extending at least half the axial length of the needle cap and extending proximally from the distal portion of the needle cap. At least two long arms may be used on the needle cap. The at least one long arm of the needle cap may be used to trigger the expulsion of a drug or for other purposes.

[0051] The needle cap may include at least one connecting arm that is coupled to a pre-injection support member, such as to a stabilizing arm(s), to switch it from a first state to a second state. The connecting arm on the needle cap may also extend proximally from a distal portion of the needle cap (e.g., the needle protection portion). The connecting arm of the needle cap may be much shorter than the at least one long arm extending proximally, for example, to activate drug / agent injection. Therefore, the at least one connecting arm may be formed as a short arm on the needle cap.

[0052] Pre-injection support or stabilization can preferably be performed on the distal portion or distal part of the drug reservoir and / or drug delivery element.

[0053] According to an embodiment, the at least one support member may include an axial support member configured to axially support the drug delivery element, for example, via a drug reservoir. The axial support member may include at least one support arm that may extend in a distal direction, preferably from a proximal portion of the housing, for example from a rear portion of the housing inserted into the housing during assembly of the drug delivery device.

[0054] The axial support member may extend parallel to or substantially parallel to the longitudinal axis of the drug delivery device. "Substantially parallel" may mean that the angle between the longitudinal axis of the axial support member and the longitudinal axis of the drug delivery device is, for example, in the range of 0 to 3 degrees. However, other arrangements of the axial support members that are not parallel or substantially parallel may also be used.

[0055] The drug delivery element can be axially supported by an axial support member, for example, indirectly supported via a drug reservoir. Furthermore, the axial support member can also provide radial support, or it can provide only axial support without radial support. These two variations are described in more detail below.

[0056] The axial support of the axial support member can be in two axial directions, such as in the distal direction and in the proximal direction. Alternatively, the axial support can be in only one axial direction, such as only in the distal direction and not in the proximal direction, or only in the proximal direction and not in the distal direction. The first variation is described in more detail below, for example, by using at least one line (rope) or filament. The second variation can be feasible in a similar manner compared to the first variation.

[0057] According to another embodiment, the drug delivery device may include a plunger or piston rod configured to transmit force to a drug contained within a drug reservoir. When the plunger is in a pre-injection state, the at least one axial support member or axial support arm may extend along and / or parallel to the plunger / piston rod. The at least one axial support member or axial support arm may have a corresponding distal portion that will be or is configured to position the drug reservoir in an axial position. The at least one axial support member or axial support arm may allow radial movement of the portion of the drug reservoir closest to the at least one axial support member or axial support arm, or closest to at least two axial support arms. Relative radial movement of the drug reservoir and / or drug delivery member relative to the housing and / or relative to the at least one support member / arm may be possible.

[0058] The axial support member can be configured to define / limit the axial position of the drug reservoir and / or drug delivery member within or relative to the housing, or can define / limit the axial position of the drug reservoir within the housing at least in the distal direction or in both the distal and proximal directions.

[0059] Axial support members / arms can be rigid or flexible, such as elastically flexible.

[0060] As described above, the axial support member / arm may extend from the proximal portion of the housing or from the rear portion of the housing into which it is inserted. Alternatively, however, other portions may be arranged between the proximal portions of the axial support member / arm(s) and the proximal portion of the housing, or between the rear portions of the housing (rear subassemblies). This will be described in more detail below, for example, regarding the flexible portions of the connecting elements, which may be elastic, such as elastic wires, or may not be elastic, such as filaments.

[0061] According to an embodiment, the at least one axial support member / arm may carry a low-friction material that allows the drug reservoir and / or drug delivery element to move radially relative to the at least one support member / arm with lower frictional force compared to the main material of the at least one support arm. The low-friction material may include PTFE (polytetrafluoroethylene) or another suitable material (e.g., grease, etc.) or be composed of the latter. The low-friction material may be a separate layer of material that can be applied to the base material of the axial support member / arm. The base material may be different from the low-friction material; for example, the low-friction material may be applied using two-component injection molding. The low friction between the proximal end of the drug reservoir (e.g., the proximal end of the proximal face of the drug reservoir flange) and the distal end of the at least one support arm may allow easy radial movement of the drug reservoir and / or drug delivery element relative to the housing, thereby, for example, reducing pain during needle insertion, injection, and / or needle retraction.

[0062] According to an embodiment, the at least one support arm may carry a ball bearing or other bearing including rolling elements at its distal end, such as a proximal ball bearing disposed on the proximal surface of the syringe flange. The ball bearing may axially, preferably via a drug reservoir, support the drug delivery element. Further, the ball bearing may allow radial displacement / movement of the drug reservoir / drug delivery element relative to the axial support member / arm. The proximal side of the syringe flange or drug reservoir may form an abutment surface for the balls of the ball bearing. Alternatively, the ball bearing may be mounted on the proximal side of the drug reservoir, and the balls may abut against the distal end of the axial support member / arm.

[0063] A second or distal ball bearing can be arranged on the distally facing surface of the syringe flange, thereby providing improved radial freedom of movement. The balls of this ball bearing can abut against the proximal facing surface of the housing. Alternatively, the distal ball bearing can be mounted on the proximal facing surface of the housing or inner housing, and the balls can abut against the distally facing surface of the syringe flange.

[0064] According to another embodiment, the drug delivery device may include an inner housing disposed within a housing, which may be referred to as an outer housing. The inner housing may simplify the assembly of the drug delivery device or may have other technical effects.

[0065] The soft material and / or flexible retaining portion may be arranged at least partially or completely within the inner shell. The soft material and / or flexible retaining portion may be held by the inner shell.

[0066] The inner housing may include a proximal face that can support a ball bearing or serve as the abutment surface for the balls of a ball bearing disposed on a flange of a drug reservoir, preferably an syringe barrel. The ball bearing may be a distal ball bearing used in addition to the proximal ball bearing described above. Alternatively, a circumferential flange disposed on the inner side of the outer housing may serve as the abutment surface for supporting a ball bearing or forming the balls of a ball bearing (e.g., a distal ball bearing).

[0067] According to an embodiment, the at least one support arm may include an orifice at its distal end. This orifice may be configured to engage with a flange of a drug reservoir, preferably with a flange of a syringe. The orifice may engage with a portion of the flange, for example, a portion of the flange may be housed within the orifice. A clearance (playback) between the sidewall of the orifice and the flange may provide freedom for pivoting and / or radial displacement of the drug container / drug delivery element. Alternatively, the flange portion may not have a clearance (playback) within the orifice. However, relative movement of the drug container relative to the axial support member / arm is possible due to the flexibility of the axial support member or for other reasons.

[0068] Similarly, the support arm can extend from the proximal portion of the housing or from the rear portion of the housing into which it is inserted. The support arm including the orifice can be rigid or flexible. The support arm can have a thinner portion compared to adjacent portions. The thinner portion can promote or increase the flexibility of the support arm.

[0069] According to an embodiment, the proximal end of the at least one support arm can be connected to a proximal portion or a rear portion of the housing via at least one connecting element, such as the rear portion inserted into the housing. The connecting element can be configured to transmit no axial pressure or a smaller axial pressure compared to the axial tensile force it can transmit. Preferably, the at least one connecting element may comprise or be composed of at least one filament. The filament may comprise, for example, plastic, textiles, or other suitable materials, or may be composed of them. Several filaments may be woven or braided together to form the connecting element. The tensile strength of the connecting element may be less than, equal to, or greater than the tensile strength of the support arm. Alternatively, a wire, such as one made of or containing metal, may be used. The wire may be elastic or may not be elastic. Thus, by using this connecting element, an axial support member / arm that can be radially displaced / moved relative to the longitudinal axis of the housing can be provided, thereby allowing radial displacement of the drug reservoir / drug delivery member relative to the housing, or conversely, allowing radial displacement of the housing relative to the drug reservoir / drug delivery member. Therefore, axial support members can contribute to pain relief or other medical benefits during the use of drug delivery devices.

[0070] The connecting elements can bridge axial distances ranging from 5 mm to 30 mm.

[0071] Axial force may be transmitted in one direction, either solely or primarily, by the connecting element, such as tensile force in the distal direction. Other support members may provide axial holding forces in other directions, for example, as described above: radial support members, such as soft materials, or pre-injection support members. The connecting element may be combined with embodiments of axial support arms, wherein the distal portion of the support arm includes at least one orifice for a flange of the injection barrel.

[0072] Elasticity can mean that the corresponding elastic part has a first shape (structure) before a force is applied. Applying a force can cause the part to take on a second shape or a second structure. After the force is removed, the part can return to or can relax back to the first shape (structure), preferably without the application of another force, i.e., in a self-relaxing manner.

[0073] Examples of elastic, flexible materials / parts that can be used as connecting elements are, for example, plastic or metal leaf springs. Tensile forces can also be transmitted. However, compressive forces can only be transmitted by the connecting element up to the point where the leaf spring is deflected (e.g., bent, such as elastically bent).

[0074] In summary, the above describes multiple support components, each of which allows for pain relief or provides other medical benefits and / or technical effects during the use of the drug delivery device, such as in relation to injection depth, injection angle, injection uniformity, etc.

[0075] According to an embodiment, the holding space for the drug reservoir and / or the drug reservoir itself may be radially surrounded by a tubular distance space, which does not include radial support elements or only includes at least one pre-injection support element removed from the drug reservoir before or during injection. The tubular distance space may extend around the drug reservoir or around the holding space of the drug reservoir, and extend along a length that is at least axial in length of the drug reservoir or at least 90% of that length. Preferably, during injection of the drug contained within the drug reservoir, the drug reservoir may not be radially supported or may only be radially supported at its proximal end.

[0076] Therefore, support for the drug reservoir and / or drug application element can be provided solely by elements of the drug delivery device arranged proximal to the drug reservoir relative to it. This allows the drug application element and / or drug reservoir to freely “float” radially, for example, during injection or during other operational phases of the drug delivery device.

[0077] The length of a drug reservoir can be measured excluding the needle or another drug application element, or including the needle or other drug application element.

[0078] According to another embodiment, the drug delivery device may include a plunger having a distal end. The distal end of the plunger and the proximal end of a plug within the drug reservoir may be configured to engage with a lateral back clearance (playback), preferably with a lateral back clearance (playback) of at least 0.5 mm or at least 1 mm. The plug may include a proximal blind hole configured to interact with the distal portion of the plunger. Alternatively, the proximal surface of the plug may be substantially flat and / or without a special blind hole that interacts with the plug during drug injection. The plunger may have a small-diameter distal portion that interacts with the blind hole. The diameter of this small-diameter portion may be smaller than the diameter of the main portion of the plunger. This small-diameter portion may have a constant diameter and may extend at least 1 mm or at least 2 mm along the longitudinal axis. Alternatively, the plunger may not have a separate small-diameter portion.

[0079] This embodiment allows for an angle between the longitudinal axis of the plunger / piston rod and the axis of the drug reservoir without the risk of jamming. However, the plug can be made of a flexible material, allowing for an angle greater than zero degrees between the two axes, with no additional backlash (clearance) or no backlash (clearance) between the distal portion of the plunger / piston rod and the blind hole within the plug.

[0080] According to an embodiment, the housing may be the outer shell of a drug delivery device. According to an embodiment, the drug delivery device may include an inner housing disposed within the outer shell. According to an embodiment, the at least one support member may be configured to further allow radial displacement of the inner housing relative to the outer shell.

[0081] Axial displacement of the inner housing relative to the outer housing may be impossible, or only possible to a lesser extent compared to radial movement between the inner and outer housings. This embodiment allows for a greater degree of radial movement compared to, for example, other embodiments. According to another embodiment, the longitudinal axis of the drug delivery container may be substantially parallel to the longitudinal axis of the plunger / piston rod, independent of radial displacement of the drug delivery element relative to the outer housing, especially during drug / pharmaceutical injection, e.g., throughout the injection phase. This avoids contact between the inner surface of the drug delivery container and the outer surface of the plunger / piston rod during drug injection. Therefore, injection can be performed in a repeatable and reliable / safe manner. Breakage of the drug delivery container, such as the glass portion breaking, can be prevented.

[0082] The at least one support member may include a soft material portion and / or a flexible holding element (e.g., an arm, beam, or sheet), as described in the embodiments mentioned above. Alternatively, a gel may be used.

[0083] According to an embodiment, the drug delivery device may include an axial support element disposed on the housing. According to an embodiment, this axial support element may be configured to allow radial displacement of the proximal end of the inner housing relative to the proximal end of the outer housing. Therefore, a greater radial displacement of the needle or drug application element relative to the housing can be achieved.

[0084] According to another embodiment, the axial support element may include a surface with a low coefficient of friction, such as a surface made of Teflon (which may be a trademark) or coated with a low-friction material. In embodiments, the axial support element may include a bearing, particularly a bearing that includes rotating elements (e.g., balls, cylinders, etc.).

[0085] According to another embodiment, the axial support element may include at least one elastic element, such as at least one spring element, particularly including or made of plastic. However, other materials may also be used, such as spring elements including or made of metal.

[0086] According to embodiments, the drug delivery device may include at least one or both of the following:

[0087] - A drive spring, which can be configured to drive the plunger or the plunger distally, or

[0088] - An axially movable needle cap that can be axially moved along the longitudinal axis of the housing or drug delivery device from a first position to a second position proximal to the first position.

[0089] Therefore, the drug delivery device can be an autoinjector that allows for easy injection, for example, the injection of drugs may not require manual driving force.

[0090] In a first position, the needle cap may cover or be configured to cover the needle (or another drug delivery element) disposed on or potentially disposed on the drug reservoir. In a second position, the needle cap is exposed or may be configured to expose the needle. The needle cap may be triggered and / or may allow drug delivery to be triggered, for example, by unlocking the plunger from a locked position / state.

[0091] According to another embodiment, a method for disconnecting a needle or other drug application element from at least a portion of a drug delivery device is disclosed. Preferably, this method can be performed to disconnect the drug application element from at least a portion of the drug delivery device according to any of the foregoing embodiments. Therefore, the same technical effects mentioned above for the drug delivery device can be applied to this method.

[0092] The method may include:

[0093] - A radial support member is used, the radial support member comprising at least one of at least one soft material for holding the drug reservoir or at least one flexible holding portion for holding the drug reservoir.

[0094] The at least one of the soft material or the at least one flexible holding portion may be configured to allow at least a portion or the entire drug reservoir to be radially displaced relative to the housing of the drug delivery device during the insertion of a drug application element disposed on or potentially disposed on the distal end of the drug reservoir into the patient’s tissue.

[0095] Therefore, the same technical effects mentioned above for drug delivery devices can be applied to this method.

[0096] The following discusses in detail the making and use of the presently preferred embodiments. However, it should be understood that this disclosure provides many applicable concepts that can be implemented in a wide variety of specific environments. The specific embodiments discussed are merely illustrative of particular ways of making and using the disclosed concepts and do not limit the scope of the claims.

[0097] Furthermore, unless otherwise specified, the same reference numerals refer to the same technical features. As used herein, the words "may" or "may" indicate or can indicate the possibility of doing so and the actual technical implementation. The present concept of this disclosure will be described below with respect to preferred embodiments in a more specific context, namely, drug delivery devices, particularly drug delivery devices for humans or animals. However, the disclosed concept can also be applied to other situations and / or arrangements, such as for lancets, syringes, pre-filled syringes, or other syringes.

[0098] The features and technical advantages of the embodiments disclosed herein have been summarized quite extensively above. Additional features and advantages of the embodiments disclosed herein will be described below (e.g., in the subject matter of the dependent claims). Those skilled in the art will understand that the disclosed concepts and specific embodiments can be readily used as the basis for modifying or designing other structures or processes for achieving the same or similar purposes as those specifically discussed herein. Those skilled in the art will also recognize that equivalent constructions do not depart from the spirit and scope defined in this disclosure, such as in the appended claims.

[0099] To gain a more complete understanding of the currently disclosed concept and its advantages, please refer now to the following description in conjunction with the accompanying drawings. The drawings are not to scale. In the drawings:

[0100] Figures 1A to 1D Cross-sections of a drug delivery device according to the first embodiment and in different operating states.

[0101] Figure 2 A general second embodiment of the drug delivery device,

[0102] Figures 3A to 3C A third embodiment of the drug delivery device,

[0103] Figure 4 Fourth embodiment of the drug delivery device,

[0104] Figure 5 Fifth embodiment of the drug delivery device,

[0105] Figures 6A to 6E Other variations of the embodiments,

[0106] Figure 7 The last embodiment, and

[0107] Figure 8. Extended structural formula, molecular formula, and molecular weight of phenotype.

[0108] A cylindrical coordinate system can be used as a reference, where each position can be defined by three coordinates: axial value (height, distance to the zero plane), radial distance to the axis, and the angle between the current radial position and the plane defined as having a zero angle. In this document, the term "at an axial position" can refer to having axial coordinates.

[0109] The term "distal" is used herein to refer to a direction, end, or surface that is arranged or is to be arranged facing or toward the dispensing end of a drug delivery device or its components and / or away from, or to be arranged away from, or away from the proximal end. Conversely, the term "proximal" is used to refer to a direction, end, or surface that is arranged or is to be arranged away from or away from the dispensing end and / or distal end of a drug delivery device or its components. The distal end can be the end closest to the dispensing end and / or furthest from the proximal end, and the proximal end can be the end furthest from the dispensing end. The proximal surface can be away from the distal end and / or facing the proximal end. The distal surface can face the distal end and / or away from the proximal end. For example, the dispensing end can be the needle tip at which the needle unit is mounted or to be mounted to the device.

[0110] The distal direction can be the direction in which the needle tip is oriented. The proximal direction can be the opposite of the distal direction. The distal and proximal directions can be aligned along the main axis. The main axis can be collinear with the needle or extend through the needle. Unless otherwise described, any or all moving parts of the injection device can be configured to move along and / or rotate about the main axis. The radial direction can be any direction orthogonal to the main axis. The main axis can be the axis along which most of the components of the injection device are arranged and / or oriented. The main axis can be the axis of the injection device with the smallest moment of inertia or at least close to such an axis.

[0111] Unless otherwise specified, reference numerals with the same last two digits may refer to the same or similar elements, such as main housing portions 102 and 302.

[0112] Embodiments may relate to drug delivery devices that include other activation mechanisms or are operated by manual driving force. Reference is made in this regard to WO 2014 / 033195 A1 or WO 2014 / 033197 A1, which are incorporated herein by reference for all legal purposes. An injection button may provide at least one user interface element for initiating and / or performing dose delivery operations of the drug delivery device. A toggle grip or knob may provide a user interface element for initiating and / or performing dose setting operations using a dose setting surface (e.g., the circumferential surface of the toggle grip or knob). A delivery surface may be used to initiate dose delivery. The delivery surface may be the proximal P-surface of the toggle grip or knob.

[0113] The device can be of the selector extension type, meaning its length can increase during dose setting or dose selection. Other injection devices with similar kinematic properties to selector extension and buttons are known during dose setting and dose dispensing operation modes, such as the Kwikpen sold by Eli Lilly. ® and Savvio ® Devices and Novo Nordisk's FlexPen® FlexTouch ® and Novopen ® 4. Devices, or devices from other manufacturers. Therefore, applying the general principles disclosed herein to these devices is straightforward, and further explanation will be omitted. Alternatively, the proposed concepts can be used in non-selective elongated devices, but include, for example, torsion springs that can be biased by rotating a selector knob. Furthermore, fully mechanically or electromechanically driven drug delivery devices can be used, such as drug delivery devices including electric motors.

[0114] However, the general principles of this disclosure are not limited to this kinematic property. Certain other embodiments are conceivable, such as those applied to other injection devices from Sanofi or other manufacturers, in which a container for the drug is present, which can be axially moved relative to the housing of the drug delivery device to insert and / or retract a needle.

[0115] Figures 1A to 1D An embodiment of a drug delivery device 100 is illustrated. Device 100 can be adapted as a device in a drug delivery arrangement further described above and below. These figures show different states of device 100 during its operation.

[0116] Figure 1A A drug delivery device 100 is shown in its initial or delivered state. The drug delivery device 100 may include a housing 102. The housing 102 may be configured to hold and / or retain a drug / medication reservoir 101a therein. A drug, such as a liquid drug or drug Dr, may be disposed in the drug reservoir 101a. The housing 102 may be configured or set to hold a needle 110 and / or retain a needle, see [reference needed]. Figure 1C In the claims, needle 110 may be referred to as a drug delivery element. However, other drug delivery elements are also possible, such as a nozzle. In other words, needle 110 may be disposed within housing 102 or may be disposed within housing. Needle 110 may be an integral part of drug reservoir 101a, for example, permanently or releasably attached to the body of drug reservoir 101a, or separate from drug reservoir 101a. In the first case, drug reservoir 101a may be a syringe, such as a PFS (prefilled syringe). In the second case, drug reservoir 101a may be a cartridge. When a cartridge is used as drug reservoir 101a, initially, drug reservoir 101a and needle 110 may be fluidly disconnected, and fluid communication between the interior of drug reservoir 101a and needle 110 may only be established during operation of drug delivery device 100.

[0117] A drive mechanism 106 may be provided to drive the drug delivery operation and may be suitably disposed within the housing 102. The drive mechanism 106 may include a plunger rod 104. The drug delivery device 100 may further include a drive energy source, such as a drive spring (e.g., a compression spring (not explicitly shown)) or gas or compressed air. The drive energy source may be arranged to drive the plunger rod 104 in a distal direction D relative to the drug reservoir 101a during the drug delivery operation. During this movement, a stopper or plug (e.g., see stopper (plug) 323a in FIG. 3) that may be movably held in the drug reservoir 101a and may seal the drug container proximally may be displaced toward the outlet of the drug reservoir 101a to dispense the drug Dr or medication held within the drug reservoir 101a through the outlet. The outlet may be formed or defined by a needle 110, see [reference needed]. Figure 1C .

[0118] Other potential driving energy sources, unlike springs, include an electric unit or battery for driving the plunger rod 104 via a motor, or a reservoir suitable for providing gas pressure, which can be used to drive drug delivery operations.

[0119] The drug delivery device 100 may be an autoinjector. The energy used to drive the drug delivery operation in the autoinjector may be provided by the components of the drug delivery device 100, rather than being applied to the device by the user during operation of the device 100, as is the case with many spring-driven pen-type variable-dose injectors, in which energy is typically applied to the spring by the user during the dose setting procedure.

[0120] The drug delivery device 100 may suitably be a single-shot device, i.e., it is used only to dispense a single dose. The drug delivery device 100 may be a disposable drug delivery device, i.e., a device 100 that is discarded after use. The device 100 may be a pen-type device. The drug reservoir 101a and / or needle 110 may be axially fixed within the drug delivery device 100 (e.g., within the housing 102) or may be movable relative to the housing 102 (e.g., for piercing the skin). In the first case, the user may have to perform the movement to pierce the skin with the needle 110. In the second case, the piercing of the skin with the needle 110 may be driven by a needle insertion mechanism of the drug delivery device 100. Automatic needle retraction may also be used. The drug reservoir 101a may be held or retained within the housing 102 by an optional holding / supporting member 101b (e.g., via a syringe carrier or other carrier for the drug reservoir 101a). Apart from the syringe and housing 102, other embodiments do not include additional syringe carriers or other drug reservoir carriers. Therefore, the drug reservoir 101a can be directly carried by the housing 102, as described in more detail below.

[0121] like Figure 1A As shown, the drug delivery device 100 may further include a cap 112. The cap 112 may be disposed at the distal end D of the drug delivery device 100. The cap 112 may be detachably connected to the remainder of the device 100, for example, to the housing 102 and / or to another component or member of the drug delivery device 100. The cap 112 may cover the distal end D and / or needle channel opening of the remainder of the drug delivery device 100 through which a needle 110 (e.g., the distal needle tip) may pierce the skin from within the drug delivery device 100 during or for the purpose of drug delivery. The cap 112 may include, for example, a needle cap / shroud remover or extractor made of metal, which may engage a rigid needle shroud / shroud RNS that may cover the needle 110, such that, for example, when the cap 112 is detached from or disconnected from the device 100, the rigid needle shroud RNS is removed from the needle 100 together with the cap 112. The housing 102 may suitably cover most of the length of the drug delivery device 100, such as 60% or 70% or higher of the total length of the drug delivery device 100 (in the case where the cap 12 is attached and / or the cap is removed).

[0122] Figure 1B A drug delivery device 100 with the cap 112 removed is shown. According to... Figure 1B The device 100 can be in a ready-to-operate state, for example, a state ready to perform a drug delivery operation when the operation is triggered. As shown, the drug delivery device 100 may further include a needle cap NC. The needle cap NC may protrude distally from the housing 102 and / or may be covered by the cap 112 while the cap 112 is still attached to the housing 102. The needle cap NC may be movable relative to the housing 102 from an initial position or a first position to a second position or a triggered position. The needle cap NC may be configured to extend beyond the distal tip of the needle 110 that may protrude from the housing 102 before the drug delivery operation begins, for example in the first position. The needle cap NC may be movable relative to the housing 102 in a proximal direction. During this movement, for example before the needle cap NC reaches the second position, the needle 110 may pierce the user's skin.

[0123] The needle cap NC can be used as a trigger member 108 of the drug delivery device. As a trigger member 108, the needle cap NC, when... Figure 1B The initial position or first position shown is shifted proximally to the second position or trigger position (see...). Figure 1CWhen the needle cap 104 is in the second position, the drug delivery operation of the drug Dr can be automatically initiated. The drug delivery operation can be initiated by removing a mechanical lock that prevents the plunger rod 104 from moving in the distal direction, or by moving the plunger rod 104 to unlock the mechanical lock via the moving needle cap NC. Alternatively, the needle cap NC can be used to trigger the drug delivery operation only when moving from the first position to the second position, and suitably when in the second position. In this case, a separate triggering element (e.g., a trigger button on the proximal end of the housing 102) can be provided to initiate the drug delivery operation. The trigger button can only be operated to initiate the drug delivery operation of the drug Dr when the needle cap NC is in the second position. In yet another alternative, only the needle cap NC can be provided to prevent needle pricks before and / or after using the drug delivery device 100. In this case, the needle cap NC can be completely disconnected from the drive mechanism 106 and / or can not participate in the triggering or implementation of the drug delivery operation at all.

[0124] The needle cap NC can be configured to rest against the user's skin during injection. Therefore, the distal surface of the needle cap NC can provide a support surface or support surface BF. The support surface BF can define and / or extend around a needle channel opening disposed in the needle cap NC. The support surface 16 can be annular, oval, elliptical, rectangular, square, etc., and is circumferentially closed and / or defined by inwardly projecting radially inward from the inner wall of the needle cap NC (e.g., its distal cylindrical portion). The support surface BF can suitably be the distal surface of the needle cap NC, for example, facing distally.

[0125] Figure 1C The needle cap NC is shown in a second position relative to the housing 102. This is, for example, the position when drug delivery operation has been initiated, can be initiated, and / or when the needle pierces the skin. The needle 110 can protrude axially from the support surface BF of the drug delivery device 100 (specifically through the needle channel opening in the needle cap NC) and pierce the skin by the distance it protrudes beyond the support surface BF (the skin is not shown in this figure, see, for example, see...). Figure 3B The distance to the skin (S) can be a representation of the injection depth or equal to the injection depth. The device 100 can be maintained in contact with the skin until the drug delivery operation of the drug Dr has been completed, which can be indicated by optional auditory, tactile, and / or visual cues provided by the drug delivery device 100. Optionally, the user can also be signaled to indicate the start of drug delivery.

[0126] After the drug delivery operation of Drug Dr has been completed (e.g., piston rod 104 has moved distally), device 100 can be removed from the skin (see [link]). Figure 1D The needle cap NC can be spring-loaded (not shown, see e.g., see [link]). Figure 3A The spring 336 in the device is biased toward a first position relative to the housing 102. Therefore, when the device 100 is removed from the skin, the needle cap NC can move toward the first position relative to the housing 102. The needle cap NC can move distally relative to the housing 102 (e.g., beyond its first position) into a final position, a third position, or a locked position. In this position, the needle cap NC can be suitably locked axially relative to the housing 102 to prevent movement in the proximal direction P, for example, by a locking engagement between the locking feature of the needle cap NC and the housing 102. Because the needle cap NC is axially locked, the needle cap can no longer be proximally displaced relative to the housing 102 to a second position and / or a first position. This protects the user from needle pricks after use. In this state, the device 100 can be locked, see [reference needed]. Figure 1D .

[0127] Alternatively, a movable needle cap may be omitted. Therefore, the distal device portion can rest against the user's skin. Needle injection can be performed via a needle insertion mechanism. An optional needle retraction mechanism can also be used. Triggering can be performed using a proximal triggering element (e.g., the proximal knob of the improved device 100).

[0128] The drug delivery device 100 may include an electronic unit that may be mechanically connected to a proximal region P or another region of the drug delivery device 100. The electronic unit may be used not only in the drug delivery device 100, but also in other drug delivery devices similar to or identical to the drug delivery device 100. Alternatively, the electronic unit may be an integrated part of the drug delivery device 100. The electronic unit may be used to monitor drug delivery, such as the amount, time, and date of the dose.

[0129] 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.

[0130] 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.

[0131] 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.

[0132] 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.

[0133] 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.

[0134] 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.

[0135] 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.

[0136] 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.

[0137] 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.

[0138] Examples of DPP4 inhibitors are liraliptin, vedagliptin, sitagliptin, degliptin, saxagliptin, and berberine.

[0139] 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.

[0140] 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.

[0141] 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).

[0142] 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.

[0143] 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.

[0144] 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).

[0145] Other 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 fentocilan. The terms "prevention" and "prophylactic treatment" are used interchangeably herein.

[0146] It is also considered that a pharmaceutically acceptable salt of any API described herein may 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.

[0147] 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.

[0148] 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 multi-dose container systems and single-dose (partially or completely emptied) container systems. The container may be a replaceable container or an integrated, non-replaceable container.

[0149] As further described in ISO 11608-1:2014(E), a multi-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 multi-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).

[0150] 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 emptied (completely emptied). In another example, each container contains a single dose, in which a portion of the deliverable volume is emptied (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 emptied (completely emptied). In another example, each container contains a single dose, in which a portion of the deliverable volume is emptied (partially emptied).

[0151] Fetrazol as an API in the device

[0152] 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.

[0153] 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.

[0154] The two nucleotide chains of non-fortuccinyl are shown below:

[0155] 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

[0156] 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),

[0157] in

[0158] Af = 2'-deoxy-2'-fluoroadenosine

[0159] Cf = 2'-deoxy-2'-fluorocytidine

[0160] Gf = 2'-deoxy-2'-fluoroguanosine

[0161] Uf = 2'-deoxy-2'-fluorouridine

[0162] Am = 2'-O-methyladenosine

[0163] Cm = 2'-O-methylcytidine

[0164] Gm = 2'-O-methylguanosine

[0165] Um = 2'-O-methyluridine

[0166] "-" (hyphen) = 3'-5' phosphate diester-linked sodium salt

[0167] "-ps-" = 3'-5' thiophosphate-linked sodium salt

[0168] And L96 has the following formula:

[0169] (I).

[0170] As used herein, the terms “2’-deoxy-2’-fluoroadenosine” and “2’-fluoroadenosine” are used interchangeably.

[0171] As used herein, the terms “2’-deoxy-2’-fluorocytidine” and “2’-fluorocytidine” are used interchangeably.

[0172] As used herein, the terms “2’-deoxy-2’-fluoroguanosine” and “2’-fluoroguanosine” are used interchangeably.

[0173] As used herein, the terms “2’-deoxy-2’-fluorouridine” and “2’-fluorouridine” are used interchangeably.

[0174] The expanded structural formula, molecular formula, and molecular weight of phenotype are shown in Figure 8.

[0175] The structure of non-tocopherol can also be described by the following diagram, where X is O:

[0176] .

[0177] Fetocetamol is shown in Figure 8 as a sodium salt.

[0178] 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.

[0179] The term “deliver / delivers / delivering” is intended to mean “administer / administers / administering”.

[0180] Unless specifically stated or otherwise 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.

[0181] 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).

[0182] 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 consists of or substantially consists 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.

[0183] In some embodiments, the non-folic acid phosphate formulation in the device for subcutaneous delivery contains non-folic acid phosphate phosphate buffer at pH 7.0 with 0.64 mM NaH₂PO₄, 4.36 mM Na₂HPO₄, and 84 mM NaCl. In some embodiments, the pharmaceutical formulations of the non-folic acid phosphate phosphate solution for subcutaneous delivery are shown in Table 1 below:

[0184] Table 1. Exemplary non-toxican pharmaceutical preparations

[0185]

[0186] Appropriate amount: Appropriate amount

[0187] In some embodiments, pharmaceutical formulations for subcutaneous delivery of non-tuzelan solutions using a device may be described, as shown in Table 2 below.

[0188] Table 2. Exemplary non-toxican pharmaceutical preparations

[0189]

[0190] 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).

[0191] 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.

[0192] 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.

[0193] 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.

[0194] 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.

[0195] 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.

[0196] 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.

[0197] 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).

[0198] 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).

[0199] 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).

[0200] 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).

[0201] 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).

[0202] 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).

[0203] 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).

[0204] 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).

[0205] 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).

[0206] 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).

[0207] 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).

[0208] Figure 2 A general second embodiment of a drug delivery device 200, such as drug delivery device 100, is shown. Drug delivery device 200 may include:

[0209] - A drug reservoir 201a, such as a medicine container 101a, and / or

[0210] - Retaining / supporting member 201b, which holds the drug reservoir in place, and / or

[0211] - Housing 202, for example, similar to housing 102.

[0212] As indicated by the two arrows Arr2a and Arr2b, relative radial movement in the radial direction R of the drug reservoirs 101a, 201a and / or needle 110 and housing 202 is possible due to at least one of the measures mentioned in this specification. These measures are, for example:

[0213] - Use soft materials and / or flexible retaining components, and / or

[0214] - Using proximal support arms, these proximal support arms can support the drug reservoir 101a, 201a at the proximal end, for example on the flange of the syringe or on another proximal portion.

[0215] Therefore, this disclosure describes the concept of disconnecting the needle 110 and / or prefilled syringe (PFS) or other drug reservoir 101a, 201a in an automated injection pen or other drug delivery device 100, 200 from the housing 102, 202.

[0216] This disclosure can be used for automated injection pens or for manually driven pens. From the user's perspective, the use of devices 100, 200 will be the same as or can be the same as the use of known drug delivery devices. Disconnection of needle 110 allows needle 110 to float freely to a certain extent perpendicular to the injection axis A.

[0217] Furthermore, this disclosure aims to alleviate injection pain that may be caused to patients due to slight axial and / or radial movement that may occur during injection. These movements may be due to hand tremors or intentional or unintentional movement. This disclosure appears particularly relevant to patients who have difficulty keeping the device still (e.g., those with Parkinson's disease), elderly patients who self-administer medication, infants, and young children.

[0218] By disconnecting the needle 110 from the housing 102, the use of devices 100, 200 (e.g., including syringe 323 PFS) becomes significantly more comfortable for the user due to less or no force between the user's skin and the needle 110. While current development may focus on autoinjectors and free-floating mechanisms for primary drug packaging, it could also be applicable to any needle-based injection system, regardless of how it is actuated or by whom the drug is administered.

[0219] Figures 3A to 3C A third embodiment of a drug delivery device 300 (e.g., drug delivery devices 100, 200, etc.) is shown. The drug delivery device 300 may include a main housing portion 302 or body, such as a cylindrical housing 302 or a substantially cylindrical housing 302. A piston rod or plunger 304, which may correspond to a piston rod 104, may be arranged in the proximal portion of the housing 304. The piston rod 304 may have a tubular shape.

[0220] The inner housing 327 may be disposed within the housing 302. The inner housing 327 may be shorter than the main housing 302; for example, its axial length may be less than half the axial length of the housing 304. The inner housing 327 may have a proximal flange that extends radially inward from the wall of the inner housing 327, for example forming the inner surface of the wall of the inner housing 327.

[0221] The soft material 321 can be disposed within the inner housing 327. Therefore, the soft material 321 does not need to be in direct physical contact with the housing 302. The soft material 321 can form a radial support member configured to radially support the drug reservoir 323 during injection of a drug Dr that can be contained within the drug reservoir 323. The drug reservoir 323 can be disposed within the holding space RS.

[0222] The soft material 321 may have a Shore A hardness of less than 90, 85, 80, 75, 70, 65, 60, 55, or less than 50, and / or may include one of the materials mentioned in the first part of the specification. Furthermore, the soft material 321 may have a tubular shape. The inner cavity of the tube may be surrounded by the wall of the tube. The inner cavity of the tube may form a holding space RS for holding the drug reservoirs 101a, 323.

[0223] The drug reservoir 323 may be a pre-filled syringe pf. A resilient stopper (plug) 323a may be arranged to move within the drug reservoir 323 pf and to close the drug reservoir 323 proximally. A plunger 304 may interact with the stopper 323a to expel the drug Dr contained within the drug reservoir 323 through a needle 310 corresponding to the needle 110. An optional blind hole may be arranged in the proximal face of the stopper 323a.

[0224] The prefilled syringe PFS may include a distal tapered portion for holding the needle 310, an intermediate cylindrical portion (e.g., a cylindrical portion), and a proximal flange Fl. The flange Fl may have a circular shape or a circular shape including two optional flat surfaces on the opposite radial side or side of the flange Fl.

[0225] The drug delivery device 300 may include an axially movable needle cap (shroud) 324 NC. The needle cap 324 NC may include:

[0226] - A distal tubular portion comprising a distally facing support surface BF adapted to contact the patient's skin S. See also: Figure 3B ,

[0227] - Two proximal arms 324a, such as the long arms of the needle cap 324 NC, extend from the distal tubular portion to the proximal end 324b of the needle cap NC. In the inactive state of the plunger 304, the proximal end 324b can be positioned near the proximal end of the plunger / piston rod 304. Therefore, the needle cap NC can be used to trigger injection of drug Dr by unlocking the plunger 304, or it can achieve injection by unlocking the plunger 304.

[0228] - At least two arms 331, such as the short arm 331 described in more detail below.

[0229] The drug delivery device 300 may include a rear subassembly or rear portion 325 that can be inserted into a proximal opening of the housing 302. The rear subassembly 325 may include:

[0230] - Optional rod 325a, which can be arranged within the hollow cavity of plunger 304, and

[0231] - The two arms 328 are described in more detail below.

[0232] A first low-friction element 326a (e.g., a first ball bearing BB) may be disposed on the distal end of arm 328. The balls of the ball bearing BB may abut against the proximal face of flange Fl. A second low-friction element 326b (e.g., a second ball bearing BB) may be disposed on the distal face of flange Fl or on the flange of inner housing 327. In a first variant, the balls of the second ball bearing BB may abut against the distal face of flange Fl. In a second variant, the balls of the second ball bearing BB may abut against the flange of inner housing 327. Instead of inner housing 327, a flange similar to that of inner housing 327 but disposed on housing 302 may be used. However, inner housing 327 simplifies the assembly of drug delivery device 300, particularly the assembly of the ball bearings BB.

[0233] Instead of the first ball bearing BB and / or the second ball bearing BB, a flat surface can be used, such as a proximal and / or distal surface coated with a low-friction material (e.g., PTFE or grease).

[0234] Therefore, the at least one support arm 328 can carry a ball bearing BB at its distal end. The ball bearing can preferably axially support a drug delivery element, such as a needle 310, via drug reservoirs 101a, 323 PFS.

[0235] The first arm 328 may form an axial support member, such as a support arm extending distally from the rear portion 325 parallel to or along the plunger or piston rod 304. The axial support member (e.g., the first arm 328) may be configured to axially support a drug delivery element (e.g., needles 110, 310). The first arm 328 may be a rigid or flexible arm. The first arm 328 may include optional thinner portions, for example, on its inner and / or outer sides, see [reference needed]. Figure 4 The thinner portion, 428c.

[0236] The second arm 329 may be disposed on the distal portion of the housing 304. The second arm 329 may form a radial and / or axial support member, such as a hinged arm or a pre-injection support member. The second arm 329 may be rigid or flexible.

[0237] Therefore, the aforementioned at least one support member may include at least one pre-injection support member, such as two second arms 329. This at least one pre-injection support member (e.g., arm 329) may be configured to be in a first state before the drug application element (e.g., needles 110, 310) is inserted into the tissue of the patient's Pat. The at least one pre-injection support member 329 may be configured to be in a second state when the drug application element (e.g., needles 110, 310) is inserted into the tissue of the patient's Pat. Figure 3A In the first configuration shown, the pre-injection support member (e.g., arm 329) can radially and / or axially support the drug delivery element (e.g., needle 310). This support can be indirect, via support of the drug reservoir / container 323 PFS, for example, on the distal portion of the cylindrical section of the drug reservoir 323 PFS. Figure 3B In the second state shown, the pre-injection support member does not support the drug application element (e.g., needles 110, 310), or provides less support to the drug application element (needles 110, 310) compared to the support in the first state.

[0238] The needle cap 324 NC may include a recess 330 on its inner side. The recess 330 may be complementary to the arm 329, for example, at least on the sides facing each other or pointing towards each other.

[0239] The needle cap 324 NC may include a third arm 331. The third arm 331 may extend proximally from the tubular portion of the needle cap 324 NC. The third arm 331 may be a rigid arm or a flexible arm. The third arm 331 may have the same angular position as the second arm 329. Thus, when the needle cap 324 NC moves proximally during the insertion of the needle 310 into the skin S of the patient's Pat, the second arm 329 may be moved into the recess 330 by the third arm 331.

[0240] The drug delivery device 300 may consist of only two springs:

[0241] - Drive spring 334, which can drive the plunger or piston rod 302 during injection, and

[0242] - Needle cap spring 336, which can bias needle cap 324 NC to the distal direction D.

[0243] The drive spring 334 may be disposed within the piston rod 304, for example, on an optional rod 325b. Alternatively, the drive spring 304 may be disposed on the outside of the piston rod 304. The drive spring 334 may abut against the proximal surface at the bottom of the inner cavity of the piston rod 304 and against the distal surface of the rear subassembly / rear portion 325.

[0244] A needle cap spring 336 may be disposed within the distal tubular portion of the needle cap 324 NC. The needle cap spring 336 may surround the distal portion of the conical portion and / or cylindrical portion of the needle 310, the drug reservoir 323, and / or the body portion. The needle cap spring 336 may abut against the inner bottom surface of the tubular portion of the needle cap 324 NC and against a protrusion 338, which will be described in more detail below.

[0245] The housing 304 may include an inner support protrusion 338, such as a circular protrusion extending along the entire circumference or a portion of the circumference of the inner surface of the housing 304. The support protrusion 338 may, for example, support the soft material 321 and / or the inner housing distally during injection.

[0246] The distal length L1 of the cylindrical portion of the drug reservoir 323 PFS may not be covered by the soft material 321. Conversely, the proximal length L2 may be covered by the soft material 321. The sum of lengths L1 and L2 may be the total length of the drug reservoir 323 PFS, such as the total length of the glass portion of the reservoir 323 PFS. Length L1 may be shorter than length L2. However, length L2 may be at least one-quarter of length L. Other possibilities for the value of length L2 are mentioned in the first part of the specification. If length L corresponds to the total length of the glass body of the syringe 323 PFS or to the total length of another drug container, the same ratio of lengths L1, L2, and length L may be applied.

[0247] Figure 3B The second state of the drug delivery device 300 is shown, for example, with the needle cap 324 NC in its second position, see proximal end 324b, which has been moved proximally a distance D3, see double-headed arrow. The drug delivery device 300 presses against the patient Pat's skin S, thereby moving the needle cap 324 NC proximally. The basic operating principle of the drug delivery device 300 can be the same as that in known autoinjectors or other known drug delivery devices. The plunger 304 can be triggered by the axial displacement of the needle cap 324 NC. Soft material 321 can surround the syringe barrel 323 PFS and can isolate it from the housing 302. Due to the low Shore A hardness of soft material 321, wobbling of the syringe barrel 323 in the radial R direction is possible.

[0248] Positioning of the injection cartridge 323 PFS in the axial direction A can be achieved by positioning the flange Fl between the arm 328 of the rear subassembly 325 and the inner housing 327. The contact surfaces can be on (a plurality of) low-friction elements 326a, 326b, such as at least one axial ball bearing BB or at least one PTFE-coated surface. This allows for radial movement of the PFS 323 while maintaining its axial position.

[0249] The two arms 329 (e.g., flexible arms) can center the needles 110, 310 before piercing the skin S. During the injection phase, the needle cap 324 NC can disconnect the arms 329 from the syringe 323, and the syringe 323 PFS can be disconnected from the radial movement of the body or housing 302. During injection, the flexible arms 329 that stabilize the PFS 323 radially and / or axially can be pushed into the recesses 330 in the body / housing 302 by the needle cap 324 NC. This allows the syringe 323 PFS to be disconnected in the radial R direction.

[0250] Due to the use of arms 328, 329 and / or 331 and / or due to the use of soft material 321 and low-friction elements 326a, 326b, the drug reservoir 323 PFS can radially “float” during injection. For example, this allows for relative radial movement or displacement between the housing 304 and the drug reservoir 323 PFS carrying needles 110, 310, for example, to alleviate pain in patient P and / or achieve the other medical advantages and technical effects described above. Radial “floating” can, of course, be achieved using more or fewer measures or other means. Arms 329 and / or 331 can be omitted. Alternatively, soft material 321 and / or inner housing 327 can be omitted. Omitting arm 328 can also be an option.

[0251] Figure 3C The device 300 was displayed. Figure 3B The section shown is on section CC. An example of a ball bearing BB that can be used as a low-friction element 326a and / or 326b is illustrated. Ball bearing BB may include:

[0252] - Ball bearing 340, for example, at least three balls or at least eight balls.

[0253] - A cage 342 that can hold the ball 340 in place, and

[0254] - An optional housing portion that can carry the cage 342 and / or can be used to mount the ball bearing BB. Alternatively, the cage 342 can have a receiving function and / or a mounting function.

[0255] Figure 4A fourth embodiment of a drug delivery device 400, such as drug delivery device 100, is shown. Drug delivery device 400 may include parts identical or similar to those of drug delivery devices 100, 200, or 300, such as parts 302 (main housing portion) to 324 (needle cap NC), 324a, 324b, etc., especially arms 329 and 331. The soft material 421 is modified compared to soft material 321. Soft material 421 is held in place without a separate inner housing. Therefore, soft material 421 can be adjacent to the housing 302 (body) of drug delivery device 400, for example, in direct physical contact. However, in another embodiment, an inner housing may also be used in drug delivery device 400. This inner housing may or may not have a proximal flange, as the design of arm 428 differs from that of arm 328.

[0256] The rear sub-assembly / rear portion 425 can be similar to the rear assembly 325. Therefore, an optional rod 325a may also be present in the rear assembly 425.

[0257] Two arms 428 can be used instead of arm 328. At least one support arm 328 or both arms 328 may include an orifice 428a on their distal end 428b. The orifice 428a may be configured to connect to a flange Fl of the drug reservoir 101a, 323 PFS, preferably to a flange Fl of the syringe PFS. The distal portion 428b of the arm 328 may be disposed distal to the flange Fl. Additionally, an optional thinner portion 428c may be disposed on the arm 328, for example, to improve the flexibility of the arm 328. Similarly, the arm 328 may be rigid or flexible.

[0258] therefore, Figure 4 Another variation of the axial positioning of the syringe 323 PFS is shown, for example, via a flexible design of the arm 428 of the rear subassembly 425. The flange Fl of the syringe 323 can be clamped in the arm 428 of the rear subassembly 425. The flexible design of the arm 428 allows for movement of the distal end 428b of the arm 428 and / or the proximal portion of the syringe 323 PFS in the radial R direction.

[0259] Similarly, the disengagement of needle 310 can be achieved by using arms 329, 331, soft material 321, and / or using arm 428 and / or the thinner portion 428c. Disengagement of needle 310 can reduce pain for patient P and / or provide other medical and / or technical benefits. Radial "floating" can, of course, be achieved using more or fewer measures or other methods. Therefore, arms 329 and / or 331 can be omitted. Alternatively, soft material 321 can be omitted.

[0260] Figure 5A fifth embodiment of a drug delivery device 500, such as drug delivery device 100, is shown. Drug delivery device 500 may include parts that are the same as or similar to those of devices 100, 200, 300, and 400, such as portions 302 (main housing portion) to 324 (needle cap NC), 324a, 324b, etc., especially arms 329 and 331. Soft material 421 may also be used in device 500, for example, without an inner housing. However, an inner housing may of course be used in device 500.

[0261] The rear subassembly 525 may be similar to the rear subassembly / rear portion 325. Therefore, an optional rod 325a may also be present in the device 500 to guide the piston rod 304 and / or drive spring 334 to move distally.

[0262] The first arm 528 can be rigid or flexible. The first arm 528 may have an aperture 458a and a distal portion 528b. Therefore, the distal end of arm 528 can be similar to or the same as the distal end of arm 428. However, arm 528 does not extend to the rear subassembly 525, but only to the connecting element disposed between the respective arm 528 and the rear subassembly 525. An optional second portion 528c may be present proximal to the connecting element. Alternatively, the proximal ends of (multiple) connecting elements may be disposed directly on the rear subassembly 525.

[0263] (Multiple) connecting elements may include at least one filament (rope) 528d. Alternatively, the aforementioned filament or other elements may be used as connecting elements.

[0264] Therefore, the proximal end of the at least one support arm 328 can be coupled to a proximal portion of the housing 102 or a rear portion 525 of the housing 102, which can be inserted into the housing 102 via at least one connecting element. The connecting element can be configured to not transmit axial pressure or to transmit a smaller axial pressure compared to the axial tensile force it can transmit. As already mentioned, the at least one connecting element may include or be composed of at least one filament.

[0265] The connecting element can bridge the axial distance D5, for example, in the range of 5 mm to 30 mm or in the range of 10 mm to 20 mm.

[0266] Similarly, this can be achieved by using arms 329, 331, soft material 321 and / or using arm 528 and / or a similar thinner portion 428c (see [link to documentation]). Figure 4The needle 310 can be disconnected by using a thinner portion and / or connecting element (e.g., filament 528d). Disconnection can reduce pain for patient P and / or provide other medical and / or technical benefits, such as those described above. Radial "floating" can, of course, be achieved using more or fewer measures or other means. Therefore, arms 329 and / or 331 can be omitted. Alternatively, soft material 321 can be omitted.

[0267] Therefore, another variation of axial positioning of PFS 323 could be connecting the element holding flange Fl to the rear subassembly 525 via a cord or wire 528d. The cord or wire 528d could only transmit tension, for example, holding the syringe 323 PFS in place when the plunger 324 is released. Further, the cord or other connecting element could radially and pressure-wise disengage the syringe 323 PFS. In this case, the pressure on the syringe 323 PFS during needle insertion could be maintained by a flexible arm 329 designed to position the syringe 323 PFS before injection begins and / or by a soft material 421. Additionally or alternatively, the plunger 304 could provide axial support during needle insertion of needles 110, 310.

[0268] Figures 6A to 6E Variations of other embodiments are shown. For example... Figure 6A As shown, disconnection allows the housings 102, 202, etc., to pivot relative to axis A2 of the drug reservoirs 101a, 202a, etc., or conversely, preferably during use of the drug delivery devices 100 to 500, such as during injection. Therefore, an angle An2 can exist between axis A2 and longitudinal axis A of the drug delivery devices 100 to 500, the value of which is in the range of 1 degree to 5 degrees or another suitable range.

[0269] Figure 6B A retaining portion HPb, which can be used in place of the soft material 321, is shown in drug delivery devices 100 to 500. At least three retaining portions, or at least four retaining portions HP1b to HP4b, or more than four retaining portions, can be used. These retaining portions can all have the same design or can have different designs from each other. These retaining portions can extend radially inwards only, or radially and axially from the housing 102, etc., extending into the holding space RS or into the drug reservoirs 101a, 323, etc. Thus, the retaining portion can be a radially extending arm. Figure 6B Four different designs were showcased:

[0270] - The fixed portion of HP1b may not include a special free end.

[0271] - The retaining portion HP2b may include an arc-shaped free end.

[0272] - The retaining portion HP3b may include a straight free end, which is arranged perpendicular to the main portion and / or axis of the retaining portion HP3b, and

[0273] - The retaining portion HP4b may include a soft end or a hard end portion, for example, in a spherical or hemispherical shape.

[0274] These free ends can be configured to physically contact, or may contact, drug reservoirs 101a and 323 PFS. Other designs are also possible. Retaining the free ends of portions HP1b to HP4b can prevent damage to the fragile drug reservoirs 101a and 323 PFS.

[0275] Therefore, the radial support member may include at least one flexible holding portion HP. The at least one flexible holding portion HP may include at least one flexible element. The flexibility of the flexible element may be selected such that during use of the drug delivery device 100 to 500 or another device, the at least one flexible element may be bent by a radial force. The flexible holding portion may include at least one straight element extending radially inward to at least one retaining space RS for the drug reservoirs 101b, 323, etc.

[0276] like Figure 6C As shown, a helical retaining portion HPc can be used. The flexible retaining portion HP may include a helical winding element. The helix of the helical winding portion may be parallel to the longitudinal axis A around its winding axis, or may correspond to the longitudinal axis A of the drug delivery device 100 to 500 or another device. Drug reservoirs 323 PFS, etc., may be arranged within a holding space RS, which may also be arranged within the center of the helix. The helix may be formed from an elongated arm or from a sheet as described above.

[0277] like Figure 6D As shown, a single retaining portion HPd, such as retaining portions HPb or HPc, can be used to retain the drug reservoir. The retaining portion HPd can have a length L1d that is much shorter than the length of the drug reservoir, for example, less than 30% or less than 10% of the aforementioned length L. The retaining portion HPd can be arranged on the proximal portion of the drug reservoir, for example, to allow pivoting relative to the housing 102. Alternatively, only a short tubular or annular soft material can be used as the retaining portion HPd.

[0278] like Figure 6EAs shown, at least two retaining portions HP1e and HP2e may be used in drug delivery devices 100 to 500 or another drug delivery device, see, for example, HPb, HPc or a short annular soft material portion. Adjacent retaining portions HP1e, HP2e, etc. may have an axial distance D6, which may be in the range of 5 mm to 30 mm or in another suitable range.

[0279] Figure 7 The last embodiment, namely drug delivery device 700, is shown. Drug delivery device 700 may include:

[0280] - A pharmaceutical container 701a, such as a pharmaceutical container including a flange 701c.

[0281] - Main housing portion 702, which forms an outer shell, the outer shell including, for example, a cylindrical shape or a substantially cylindrical shape.

[0282] - Inner housing portion 702b, which includes an optional distal stop element 702c.

[0283] - Piston rod 704,

[0284] - Drive mechanism 706, such as drive spring,

[0285] - Actuating elements, not shown, such as an axially movable needle sleeve (shroud), and

[0286] - Optional needle 710.

[0287] Similarly, the drug Dr can be contained within the drug container 701a. The drug Dr can be one of the drugs mentioned in the drug list above.

[0288] Soft material portions 721a and / or 721b may be arranged between the outer shell 702 and the inner shell 702b. Alternatively, a single, longer soft material portion may be used instead of both soft material portions 721a and 721b.

[0289] In another embodiment, instead of or in addition to the soft material portion 721a, flexible retaining portions HP7a to HP7d, such as arms, beams, or sheets, can be used. Additional retaining portions can be arranged in other cross-sections, for example, perpendicular to the drug delivery device 700. Figure 7 The cross-section shown can also extend through the longitudinal axis A of the drug delivery device 700. Furthermore, flexible holding portions (e.g., arms or beams) can be used in the proximal half, for example, between the wider portion of the outer shell 702 and the inner shell 702b.

[0290] The inner housing portion 702b may include two cylindrical portions. The inner housing 702b may be an integrally formed part, for example, using injection molding. In another embodiment, the inner housing may include more than one part, but at least two parts, which may be assembled together, for example, using threaded or snap-fit ​​connections or another type of connection.

[0291] Compared to the proximal portion of the inner shell 702b, the distal portion of the inner shell 702b can have a smaller diameter. The inner diameter of the distal portion of the shell 702b can be adapted to the outer diameter of the main portion of the pharmaceutical container 701a.

[0292] The inner diameter of the proximal portion of the housing 702b can be adapted to the outer diameter of the flange 701c, for example, if the flange 701c includes at least one flat portion, typically including two flat portions on opposite sides, then it is adapted to the maximum outer diameter.

[0293] In another embodiment, the inner housing 702b may have a constant or substantially constant diameter along its main length, i.e., at least 90% of its axial length. Therefore, an injection cartridge including the flange 701c can be inserted laterally, or a drug container without a flange can be used.

[0294] The piston rod 704 (e.g., a plunger) may have a hollow cylindrical shape. Therefore, a drive spring 706 may be arranged within the piston rod 704. An optional pin 740 may be used to stabilize the drive spring 706 within the piston rod 704. In another embodiment, the drive spring 706 may be arranged on the outside of the piston rod 704.

[0295] In addition, the piston rod 704 may include at least one radially extending wing or protrusion 742. The protrusion 742 can be used to release the piston rod 704 to initiate the injection of drug Dr.

[0296] The axially movable needle sleeve or cannula may include a long arm extending proximally to P. The proximal ends of these long arms may be configured to interact with at least one lateral projection of the piston rod 704. The long arms may extend within the inner housing 702b or outside the inner housing 702b but within the outer housing 702. The length of the lateral projection of the piston rod 704 may be adapted accordingly.

[0297] The rear portion 748 of the inner housing 702b can hold two rigid arms 750a, 750b, which extend distally from the rear portion 748. The rear portion 748 can be configured as a cover to close the inner housing 702b proximally. However, complete closure is optional.

[0298] Each rigid arm 750a, 750b can carry a corresponding elastic element 760, such as a spring element, particularly a plastic spring element. The elastic element 760 can be axially biased, for example, biased distally to the flange 701c or another proximal portion of the container 701a. A radial degree of freedom may exist between the elastic element 760 and the flange 701c or the other proximal portion. However, this radial degree of freedom may not be necessary within the inner housing 702b, since the inner housing 702b is radially movable relative to the outer housing 702. Axial movement between the inner housing 702b and the outer housing may be impossible, as described in more detail below.

[0299] The shape of the rear portion 780 of the housing 702 can be determined to close the cover of the housing 702 proximally. However, complete closure is optional. At least one optional arm 782 or at least one optional other support structure may be present, extending distally from the cover or rear portion 780 of the housing 702. An axial support element 784 (e.g., a ball bearing as described above, or a radially extending surface, such as a surface coated with Teflon (which may be a trademark) or other low-friction material) may be arranged on the at least one optional arm 782 or on the at least one optional other support structure on the rear portion 780. The axial support element 784 can prevent the inner housing 702b from moving proximally relative to the housing 702. However, radial movement of the inner housing, especially the proximal end of the inner housing 702b, relative to the housing 702 is possible, see arrow 790.

[0300] Compared to the other embodiments described above, this radial degree of freedom of movement can be greater. Furthermore, the piston rod 104 can always be parallel to the drug container 701a, thereby allowing for complete injection of the drug Dr within a short time. For example, contact between the piston rod 704 and the drug container 701a, especially the glass portion of the drug container 701a, can be avoided.

[0301] A step S1 may be present at the boundary between the narrower distal portion and the wider proximal portion of the inner housing 702c. The step S1 can be used to prevent distal movement of the inner housing 702c, for example, through abutment between the step S1 and the soft material 721a or a rigid retainer of the soft material 721a. However, other stop elements SE1 to SE4 may be used to prevent distal movement of the inner housing 702b. Stop elements SE1 and / or SE3 may be arranged on the outer housing 702. Stop elements SE2 and / or SE4 may be arranged on the inner housing 702c. Combinations of stop elements SE1 to SE4 may be used, for example, as long as there is radial space between the opposing stop elements on the inner housing 702b and the outer housing 702, thereby allowing radial displacement of the inner housing 702b relative to the outer housing 702. Other axial fixing elements may be used in other embodiments.

[0302] Assembly can be performed in the following ways, for example, for Figure 7 Examples shown:

[0303] - The inner housing 702b is assembled by introducing the drug container 701a (injection cartridge), drive mechanism 706, and plunger 704 together with the rear portion 748.

[0304] - The soft material portions 721a and / or 721b and / or the retaining portions HP7a to HP7b can be arranged on the outer side of the inner housing 702b before or after assembling the inner housing 702b. In an embodiment, the soft material portions 721a and / or 721b and / or the retaining portions HP7a to HP7b can be an integral part of the inner housing 702b.

[0305] - The soft material portions 721a and / or 721b and / or the retaining portions HP7a to HP7b, along with the assembled inner housing, can be inserted into the outer housing 702, and

[0306] - The outer casing 702 is enclosed by the rear portion 780.

[0307] Optional infusion steps can be performed during or after assembly.

[0308] In other words, drug delivery devices 100 to 500 or another type of drug delivery device may include:

[0309] - Housing 102, etc., for receiving drug reservoir 101a,

[0310] The drug application elements 110 and 310 may be fluidly connected to or be fluidly connected to the drug reservoir 101a, and the drug application elements 110 and 310 define the drug outlet of the drug delivery device 100 to 500, and / or

[0311] - At least one support member, which may be mechanically coupled or connectable to the drug application elements 110, 310, to support the drug application elements 110, 310 relative to the housings 102, 302.

[0312] The at least one support member may be configured to allow the housings 102, 302, etc. to be radially displaced relative to the drug application elements 110, 310 during drug delivery operations.

[0313] A method for disconnecting a drug application element (e.g., needle 110, 310, etc.) from at least a portion of a drug delivery device 100 to 500 or another drug delivery device may include:

[0314] - A radial support member 101b is used, which includes at least one of a soft material for holding the drug reservoir 101a or a flexible holding portion HP for holding the drug reservoir 101a, 323 PFS.

[0315] Among them, at least one of the soft material 321 or the flexible holding portion HP can be configured to allow at least a portion of the drug delivery element disposed on or potentially disposed on the distal end D of the drug reservoir 101a to be radially displaced relative to the housing 102, 302 of the drug delivery device 100 to 500 during insertion into the tissue (e.g., skin S) of the patient Pat.

[0316] Although the embodiments and advantages of this disclosure have been described in detail, it should be understood that various changes, substitutions, and alterations can be made therein without departing from the spirit and scope of this disclosure as defined by the appended claims. For example, those skilled in the art will readily understand that many of the features, functions, processes, and methods described herein can be changed while still remaining within the scope of this disclosure. Furthermore, the scope of this application is not intended to be limited to the specific embodiments of the systems, processes, manufactures, methods, or steps described herein. Those skilled in the art will readily understand from the disclosure that systems, processes, manufactures, methods, or steps that are currently existing or to be developed later, performing substantially the same functions or achieving substantially the same results as the corresponding embodiments described herein, can be utilized according to this disclosure. Accordingly, the appended claims are intended to include such systems, processes, methods, or steps within their scope. Further, the embodiments mentioned in the first part of the specification can be combined with the examples in the second part of the specification relating to Figures 1 through 8.

Claims

1. A drug delivery device (100), comprising: Housing (102) for receiving drug reservoir (101a). The drug application element (110) is fluidly connected to or may be connected to the drug reservoir (101a), and the drug application element (110) defines the drug outlet of the drug delivery device (100), and At least one support member is connected to or may be connected to the drug application element (110) to support the drug application element (110) relative to the housing (102). The at least one support member is configured to allow the housing (102) to be radially displaced relative to the drug delivery element (110) during drug delivery operations.

2. The drug delivery device (100) according to claim 1, wherein, The at least one support member includes a radial support member configured to radially support the drug reservoir (101a) during injection of the drug (Dr) contained in the drug reservoir (101a).

3. The drug delivery device (100) according to claim 2, wherein, The radial support member comprises a soft material, preferably at least a portion of the soft material, and The soft material (321) has a Shore A hardness of less than 90, 85, 80, 75, 70, 65, 60, 55 or less than 50.

4. The drug delivery device (100) according to claim 3, wherein, The soft material (321) includes a tubular shape, wherein the inner cavity of the tube is surrounded by the wall of the tube, and wherein the inner cavity of the tube forms a holding space (RS) for holding the drug reservoir (101a).

5. The drug delivery device (100) according to claim 2, wherein, The radial support member (101b) includes at least one flexible retaining portion (HP). The at least one flexible holding portion (HP) includes at least one flexible element, and The flexibility of the flexible element is selected such that the at least one flexible element can be bent by radial force during use of the drug delivery device (100).

6. The drug delivery device (100) according to claim 5, wherein, The flexible retaining portion (HP) includes at least one straight element extending radially inward to the retaining space (RS) for the drug reservoir (101a), or The flexible holding portion (HP) includes a spiral winding element (HPc), and The spiral of the spiral winding portion is parallel to or corresponds to the longitudinal axis (A) around its winding axis.

7. The drug delivery device (100) according to any one of the preceding claims, wherein, The at least one support member includes at least one pre-injection support member (329). The at least one pre-injection support member (329) is configured to be in a first state before the drug delivery element (110) is inserted into the patient's (Pat) tissue. The at least one pre-injection support member (329) is configured to be in a second state when the drug delivery element (110) is inserted into the patient's tissue. In this first state, the pre-injection support member (329) supports the drug delivery element (110), and In the second state, the pre-injection support member (329) does not support the drug application element (110), or provides less support to the drug application element (110) compared to the support in the first state.

8. The drug delivery device (100) according to any one of the preceding claims, wherein, The at least one support member includes an axial support member configured to axially support the drug delivery element (110), and The axial support member includes at least one support arm (328) extending in the distal direction.

9. The drug delivery device (100) according to claim 8, wherein, The at least one support arm (328) carries a low-friction material that allows the drug reservoir (101a) to move radially (R) relative to the at least one support arm (328) with a lower frictional force compared to the main material of the at least one support arm (328). Preferably, the low-friction material comprises or is composed of PTFE, and / or The at least one support arm (328) carries a ball bearing (BB) at its distal end. The ball bearing (BB) preferably supports the drug delivery element axially via the drug reservoir (101a).

10. The drug delivery device (100) according to claim 8, wherein, The at least one support arm (328) includes an opening (428a) at its distal end (428b), and The orifice (428a) is configured to connect to the flange (Fl) of the drug reservoir (101a), preferably to the flange (Fl) of the syringe (323, PFS), and / or The proximal end of the at least one support arm (328) is connected to the proximal portion of the housing (102) or to the rear portion (525) of the housing (102) via at least one connecting element. Specifically, compared to the axial tensile force that the connecting element can transmit, the connecting element is configured to not transmit axial compressive force or to transmit a small axial compressive force. Preferably, the at least one connecting element comprises or is composed of at least one filament.

11. The drug delivery device (100) according to any one of the preceding claims, wherein, The retention space (RS) for the drug reservoir (101a) and / or the drug reservoir (101a) being radially surrounded by a tubular distance space that does not include a radial support element or only includes at least one pre-injection support element removed from the drug reservoir before or during injection. The tubular space extends along at least the axial length (L) of the drug reservoir or at least 90% of that length (L), and Preferably, during the injection of the drug (Dr) contained in the drug reservoir (101a), the drug reservoir (101a) is not radially supported or is only radially supported at its proximal end.

12. The drug delivery device (700) according to any one of the preceding claims, wherein, The housing (102) is the outer housing (702) of the drug delivery device (700). The drug delivery device (700) includes an inner housing (702b) disposed within the outer housing (702), and The at least one support member is configured to also allow the inner housing (702b) to be radially displaced relative to the outer housing (702).

13. The drug delivery device (700) according to claim 12, wherein, The drug delivery device (700) includes an axial support element disposed on the housing (702), and The axial support element is configured to allow the proximal end of the inner housing (702c) to be radially displaced relative to the proximal end of the outer housing (702).

14. The drug delivery device (100) according to any one of the preceding claims, wherein, The drug delivery device (100) includes at least one or both of the following: Drive spring (334), which is configured to drive plunger (104) or plunger (104) distally. An axially movable needle cap (324, NC) is provided, which can be axially moved along the longitudinal axis (A) of the drug delivery device from a first position to a second position proximal to the first position. In the first position, the needle cap (NC) covers or is configured to cover the needle (110) disposed on or potentially disposed on the drug reservoir (101a), and in the second position, the needle cap (NC) is exposed or is configured to expose the needle.

15. A method for disconnecting a drug application element (110) from at least a portion of a drug delivery device (100), preferably from at least a portion of the drug delivery device (100) according to any one of the preceding claims, the method comprising: The radial support member (101b) includes at least one of at least a soft material for holding the drug reservoir (101a) or at least one flexible holding portion (HP) for holding the drug reservoir (101a). The at least one of the soft material (321) or the at least one flexible holding portion (HP) is configured to allow at least a portion of the drug reservoir (101a) to be radially (R) displaced relative to the housing of the drug delivery device (100) during the insertion of a drug application element (110) disposed on or potentially disposed at the distal end (D) of the drug reservoir (101a) into the tissue of a patient (Pat).

16. A drug delivery device (100), comprising: Housing (102) for receiving drug reservoir (101a). The drug application element (110) is fluidly connected to or may be connected to the drug reservoir (101a), and the drug application element (110) defines the drug outlet of the drug delivery device (100), and At least one support member is connected to or may be connected to the drug application element (110) to support the drug application element (110) relative to the housing (102). The at least one support member is configured to allow the housing (102) to radially displace relative to the drug delivery element (110) during drug delivery operations. The at least one support member includes a radial support member configured to radially support the drug reservoir (101a) during injection of the drug (Dr) contained in the drug reservoir (101a). The radial support member comprises a soft material, and The soft material extends from the inner wall of the housing (102) to the drug reservoir (101a).

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