Instructions for using the dose divider

Abstract

A method for using a dose divider comprising first and second arms, each having a front portion that jointly forms a channel for receiving a syringe plunger rod. An elastic hinge pivotably connects the first and second arms so that the dose divider is reversibly movable between a first configuration and a second configuration. In the second configuration, the dose divider is configured to receive a plunger rod in a channel formed between the front portions of the first and second arms. The channel is configured to receive a particular outer shape of the plunger rod. The front portions of the first and second arms are closer when the dose divider is in the first configuration than when it is in the second configuration. The method includes moving the dose divider from the first configuration to the second configuration by applying force to the first and second arms so that the first arm pivots in a first direction relative to the second arm using the elastic hinge.

Description

[Technical Field]

[0001] This disclosure relates to a dose divider for attachment to a syringe plunger rod, a system including a dose divider and a syringe, and a method of using the dose divider and syringe. [Background technology]

[0002] Respiratory syncytial virus (RSV) is a major cause of severe acute lower respiratory tract illness (LRI) in infants and children and is a common cause of severe pneumonia requiring hospitalization in children worldwide. Global estimates suggest that in 2015, there were approximately 33 million RSV-related LRI cases and 118,000 deaths in children under 5 years of age. It is estimated that over 80% of all RSV-related LRIs and over 50% of RSV-related deaths in low- and middle-income countries occurred in infants 6 months of age or older.

[0003] A syringe is typically a drug container that includes a container having an outlet from which the drug can be discharged during drug delivery, and a plunger rod that can be operated by the user to cause the drug to be delivered from the outlet. Such a plunger rod may include, for example, a plunger or piston within the drug container, which can be moved within the drug container to dispense the drug.

[0004] Some medications are intended to be delivered in two or more doses from a single container. In such cases, the user may need to operate the plunger rod through a first range of motion to dispense the first dose, and then operate the plunger rod through one or more subsequent ranges of motion to dispense subsequent doses. Some patients may find it difficult to operate the plunger to dispense the desired amount of medication in separate doses each time. Alternatively, patients may, due to inexperience with the device or a misunderstanding of the instructions for use, accidentally dispense an unintended amount of medication or dispense the entire amount of medication at once. [Overview of the project] [Means for solving the problem]

[0005] According to a first aspect of this disclosure, a dose divider is provided for releasably mounting on the plunger rod of a syringe, the dose divider being A first arm and a second arm opposite the first arm, each including its front portion, the front portion of the first arm and the front portion of the second arm forming a channel between them for receiving a plunger rod, To allow the dose divider to move reversibly between the first and second configurations, an elastic hinge is provided to pivotally connect the first arm and the second arm. Includes, When the dose divider is in the second configuration, the dose divider is configured to receive a plunger rod in a channel through an opening formed between the front of the first arm and the front of the second arm, and the channel has a shape configured to receive a specific outer shape of the plunger rod. The front of the first arm and the front of the second arm are closer together when the dose divider is in the first configuration than when it is in the second configuration. This may provide a dose divider that is easier for the user to control / operate. This may provide a dose divider that is easier to reposition on the plunger rod.

[0006] The elastic hinge may be configured to bias the dose divider toward the first configuration. This may provide a dose divider that securely grips the plunger rod and / or is compatible with two or more types of plunger rods.

[0007] The first arm and the second arm may each include a rear portion, and the dose divider may be configured to move from the first configuration to the second configuration by the user moving the rear portion of the first arm toward the rear portion of the second arm. This may provide a dose divider that is easy for the user to control / operate. This may provide a dose divider that is easy to reposition on the plunger rod.

[0008] The outer surfaces of the rear of the first arm and the outer surfaces of the rear of the second arm may include their respective grip configurations. This may provide a dose divider that is easy for users, such as users with reduced manual dexterity, to control / operate.

[0009] Each grip configuration may include multiple ridges. This may provide a dose divider that is easier for users, such as those with reduced manual dexterity, to control and operate.

[0010] The dose divider may further include a stop configuration located at at least one of the rears of a first arm and a second arm, the stop configuration being positioned between the first and second arms to restrict the rear of the first arm from moving toward the rear of the second arm. This may provide a dose divider that is easy for the user to control / operate. This may prevent damage to the dose divider due to the rears coming too close to each other.

[0011] The stop configuration may include a first projection located on the rear of a first arm and a second projection located on the rear of a second arm, wherein the first and second projections may be configured to come into contact with each other when the rear of the first arm is moved toward the rear of the second arm, in order to restrict the rear of the first arm from moving further toward the rear of the second arm.

[0012] The first projection may include a groove configured to receive at least a portion of the second projection when the first projection and the second projection are in contact with each other.

[0013] The front of the first arm and the front of the second arm may each include a guide surface for guiding the plunger rod through the opening toward the channel. This may provide a dose divider that is easy for the user to control / operate and facilitates mounting the dose divider to the plunger rod.

[0014] The dose divider may further include at least one of a first block protrusion and a second block protrusion disposed between the channel and the elastic hinge to prevent the plunger rod from exiting the channel. This makes it easier for the user to insert the plunger rod into the correct position within the channel and can prevent damage to the elastic hinge.

[0015] The dose divider can be integrally formed from a single piece of material, and optionally, the material is a polymer. This can provide a dose divider that is easy and inexpensive to manufacture and is easy to modify.

[0016] The dose divider can be formed by an additive manufacturing or molding process.

[0017] The elastic hinge can be formed from a polymer.

[0018] The elastic hinge can include curved portions coupled to the ends of the respective straight portions.

[0019] The elastic hinge can include curved portions coupled to the respective straight portions at their respective ends. This can provide a compact hinge having good flexibility and elastic properties.

[0020] The elastic hinge can be a living hinge integrally formed with the first arm and the second arm.

[0021] According to a second aspect of the present disclosure, there is provided a drug delivery device including a dose divider according to any of the previous disclosures and a syringe, the syringe including a plunger rod, and the dose divider being removably coupled to the plunger rod.

[0022] The syringe can include an atomizer and can be configured for nasal administration of the drug.

[0023] The drug can be an RSV vaccine.

[0024] The drug delivery device may be configured to administer the RSV vaccine nasally, with approximately 1 / 2 dose delivered to each nostril of the patient.

[0025] The drug delivery device may be configured to deliver a nasal dose of approximately 0.2 mL of RSV vaccine, with approximately 0.1 mL delivered to each nostril.

[0026] The drug delivery device may be configured to administer a second dose nasally, with approximately 1 / 2 of the dose delivered to each nostril of the patient.

[0027] The drug delivery device may be configured to deliver a second dose of approximately 0.2 mL of RSV vaccine, with approximately 0.1 mL delivered to each nostril.

[0028] The drug delivery device has an average droplet size D of about 10 - 120 μm , , , , , ,

[0031] and may be configured to deliver it.

[0029] The average droplet size D delivered to each nostril v50 may be about 10 - 120 μm, about 30 - 110 μm, about 50 - 110 μm, about 70 - 110 μm, or about 80 - 110 μm.

[0030] The drug delivery device may be configured to deliver an average shot volume of about 85 μL - about 120 μL, about 90 μL - about 115 μL, or about 9 5 μL - about 115 μL to each nostril.

[0031] According to a third aspect of the present disclosure, a method of using a dose divider is provided, the dose divider comprising a first arm and a second arm opposite the first arm, each including a respective front portion, the front portions of the first arm and the second arm forming a channel for receiving the plunger rod of a syringe, the first arm and the second arm, and an elastic hinge pivotally coupled to the first arm and the second arm such that the dose divider is reversibly movable between a first configuration and a second configuration and including When the dose divider is in the second configuration, the dose divider is configured to receive a plunger rod in a channel through an opening formed between the front of the first arm and the front of the second arm, and the channel has a shape configured to receive a specific outer shape of the plunger rod. The front of the first arm and the front of the second arm are closer together when the dose divider is in the first configuration than when the dose divider is in the second configuration. The method is, While the dose divider is connected to the plunger rod of the syringe, the plunger rod is moved within a first range of motion relative to the syringe container to dispense a first dose of the drug contained in the syringe, Remove the dose divider from the plunger rod, While the dose divider is detached from the plunger rod, move the plunger rod in a second range of motion relative to the container to dispense a second dose of the drug contained in the syringe. Includes.

[0032] A fourth aspect of this disclosure provides a method for using a dose divider, wherein the dose divider is A first arm and a second arm opposite the first arm, each including its front portion, the front portion of the first arm and the front portion of the second arm forming a channel for receiving the plunger rod of a syringe, the first arm and the second arm, Elastic hinges are pivotably coupled to the first and second arms so that the dose divider can move reversibly between the first and second configurations. Includes, When the dose divider is in the second configuration, the dose divider is configured to receive a plunger rod into a channel through an opening formed between the front of the first arm and the front of the second arm, and the channel has a shape configured to receive a specific outer shape of the plunger rod. The front of the first arm and the front of the second arm are closer together when the dose divider is in the first configuration than when the dose divider is in the second configuration. The method involves moving the dose divider from a first configuration to a second configuration by applying force to the first arm and the second arm such that the first arm pivots in a first direction relative to the second arm using an elastic hinge.

[0033] The first arm and the second arm of the dose divider may each include a rear portion, and applying force to the first arm and the second arm may include applying force to the rear portions of the first arm and the second arm such that the rear portions of the first arm and the second arm pivot toward each other, and the front portions of the first arm and the second arm pivot toward each other in opposite directions.

[0034] The rear of the first arm may include a first projection, and the rear of the second arm may include a second projection. The method is, The method further includes moving the rear of the first arm toward the rear of the second arm such that the first projection and the second projection come into contact with each other, restricting further movement of the rear of the first arm toward the rear of the second arm.

[0035] The first projection may include a groove configured to receive at least a portion of the second projection when the first projection and the second projection are in contact with each other.

[0036] The outer surface of the rear of the first arm and the outer surface of the rear of the second arm may include their respective grip configurations, and optionally, each grip configuration may include multiple ridges.

[0037] The dose divider may further include a stop configuration located at least one of the rear of the first arm and the rear of the second arm, The stop configuration is positioned between the first and second arms to restrict the rear of the first arm from moving toward the rear of the second arm.

[0038] The method may further include moving the dose divider from a first configuration to a second configuration, and then moving the dose divider to a second configuration by releasing the forces applied to the first and second arms such that the first arm pivots in a second direction opposite to the first direction relative to the second arm using an elastic hinge.

[0039] The method may further include either connecting the dose divider to the plunger rod of the syringe or detaching the dose divider from the plunger rod of the syringe while the dose divider is in the second configuration.

[0040] The method may further include moving the plunger rod within a first range of motion relative to the syringe container to dispense a dose of the drug contained in the syringe while the dose divider is coupled to the plunger rod of the syringe.

[0041] The elastic hinge may be configured to bias the dose divider toward the first configuration.

[0042] The front portion of the first arm and the front portion of the second arm may each include a guide surface for guiding the plunger rod through the opening toward the channel.

[0043] The dose divider may further include at least one of a first block projection and a second block projection positioned between the channel and the elastic hinge to prevent the plunger rod from exiting the channel.

[0044] The dose divider may be formed integrally from a single piece of material, and optionally, the material is a polymer.

[0045] The elastic hinge may include curved sections connected to their respective straight sections at each end.

[0046] The curved portion may curve away from the front end of the dose divider, such that the apex of the curved portion is located at the rear of the elastic hinge.

[0047] Elastic hinges can be arched.

[0048] The elastic hinge may be a living hinge formed integrally with the first arm and the second arm.

[0049] According to the fifth aspect of this disclosure, The vial containing the drug, A syringe including a container and a plunger rod, A needle, configured to be attached to a syringe so that a drug can be drawn from a vial into a container via the needle, An atomizer configured to be attached to a syringe, A dose divider according to any of the previous disclosures, configured to be coupled to a plunger rod and A system including this is provided.

[0050] The drugs may include vaccines.

[0051] The vaccine could be an RSV vaccine.

[0052] The syringe may be configured for nasal administration of the drug.

[0053] The system can be configured to administer the RSV vaccine intranasally, with approximately half a dose delivered to each nostril of the patient.

[0054] The system can be configured to deliver an intranasal dose of RSV vaccine at approximately 0.2 mL, with approximately 0.1 mL delivered to each nostril.

[0055] The system can be configured to administer a second dose intranasally, with approximately half a dose delivered to each nostril of the patient.

[0056] The system may be configured to deliver a second dose of RSV vaccine, approximately 0.2 mL, with approximately 0.1 mL delivered to each nostril.

[0057] The system has an average droplet size of approximately 10-120 μm. v50 It can be configured to deliver.

[0058] Average droplet size D delivered to each nostril v50 The size can be approximately 10-120 μm, approximately 30-110 μm, approximately 50-110 μm, approximately 70-110 μm, or approximately 80-110 μm.

[0059] The system can be configured to deliver an average shot volume of approximately 85 μL to 120 μL, 90 μL to 115 μL, or 95 μL to 115 μL to each nostril.

[0060] According to a sixth aspect of this disclosure, a method for using the system is provided, and the system is The vial containing the drug, A syringe including a container and a plunger rod, A needle, configured to be attached to a syringe so that a drug can be drawn from a vial into a container via the needle, An atomizer configured to be attached to a syringe, A dose divider configured to reversibly move from a first configuration to a second configuration, Includes, When the dose divider is in the second configuration, the dose divider is configured to receive the plunger rod, When the dose divider is in the first configuration, the dose divider is configured to be coupled with a plunger rod. The method is, While the needle is connected to the syringe, the drug is drawn from the vial into the syringe container via the needle, The dose divider is connected to the plunger rod, Removing the needle from the syringe, Attaching the atomizer to the syringe, While the dose divider is connected to the plunger rod and the atomizer is connected to the syringe, the plunger rod is moved within a first range of motion relative to the syringe container in order to dispense a first dose of the drug from the container out of the atomizer, After discharging the first dose of medication, remove the dose divider from the plunger rod, While the dose divider is detached from the plunger rod and the atomizer is connected to the syringe, move the plunger rod within a second range of motion relative to the container to dispense a second dose of the drug out of the container and out of the atomizer. Includes.

[0061] The dose divider may include a first arm and a second arm opposite the first arm, each including its front portion, the front portions of the first arm and the front portions of the second arm forming a channel for receiving a plunger rod between them, and elastic hinges pivotably coupled to the first arm and the second arm so that the dose divider is reversibly movable between the first and second configurations.

[0062] When the dose divider is in the second configuration, it may be configured to receive a plunger rod into a channel through an opening formed between the front of the first arm and the front of the second arm.

[0063] When the dose divider is in the first configuration, the channel may have a shape configured to receive a specific outer shape of the plunger rod.

[0064] The front portions of the first arm and the second arm may be closer together when the dose divider is in the first configuration than when it is in the second configuration.

[0065] The atomizer may be inserted at least partially into the patient's first nostril while a first dose of the drug is being dispensed, and the atomizer may be inserted at least partially into the patient's second nostril while a second dose of the drug is being dispensed.

[0066] The method may further include attaching the needle to the syringe before drawing the drug from the vial into the syringe.

[0067] The drugs may include vaccines.

[0068] The vaccine could be an RSV vaccine.

[0069] The method may include intranasal administration of the RSV vaccine, in which approximately half a dose is delivered to each nostril of the patient.

[0070] The method may include delivering an intranasal dose of approximately 0.2 mL of RSV vaccine, with approximately 0.1 mL delivered to each nostril.

[0071] The method may include administering a second dose intranasally, so that approximately half a dose is delivered to each nostril of the patient.

[0072] The method may involve delivering a second dose of the RSV vaccine in approximately 0.2 mL, with approximately 0.1 mL delivered to each nostril.

[0073] The method involves an average droplet size of approximately 10-120 μm. v50 This may include delivering [something].

[0074] Average droplet size D delivered to each nostril v50 The size can be approximately 10-120 μm, approximately 30-110 μm, approximately 50-110 μm, approximately 70-110 μm, or approximately 80-110 μm.

[0075] The method may include delivering an average shot volume of approximately 85 μL to 120 μL, approximately 90 μL to 115 μL, or approximately 95 μL to 115 μL to each nostril.

[0076] The elastic hinge may be configured to bias the dose divider toward the first configuration.

[0077] The dose divider may include a first arm and a second arm, each including a front and a rear section, and the dose divider may be configured to move from a first configuration to a second configuration by the user moving the rear section of the first arm toward the rear section of the second arm.

[0078] The outer surface of the rear of the first arm and the outer surface of the rear of the second arm may include their respective grip configurations.

[0079] Each grip configuration may include multiple ridges.

[0080] The dose divider may further include a stop configuration located at at least one of the rear of a first arm and the rear of a second arm, the stop configuration being positioned between the first arm and the second arm to restrict the rear of the first arm from moving toward the rear of the second arm.

[0081] The stop configuration may include a first projection located on the rear of a first arm and a second projection located on the rear of a second arm, wherein the first and second projections may be configured to contact each other when the rear of the first arm is moved toward the rear of the second arm in order to restrict the rear of the first arm from moving further toward the rear of the second arm.

[0082] The first projection may include a groove configured to receive at least a portion of the second projection when the first projection and the second projection are in contact with each other.

[0083] The front portion of the first arm and the front portion of the second arm may each include a guide surface for guiding the plunger rod from the opening toward the channel.

[0084] The dose divider may further include at least one of a first block projection and a second block projection, positioned between the channel and the elastic hinge, for preventing the plunger rod from moving out of the channel.

[0085] The dose divider may be formed integrally from a single piece of material, and optionally, the material may be a polymer.

[0086] The dose divider may be formed by an additive manufacturing or molding process.

[0087] Elastic hinges can be formed from polymers.

[0088] The elastic hinge may include curved sections joined at each end to each straight section.

[0089] The elastic hinge may be a living hinge formed integrally with the first arm and the second arm.

[0090] These and other aspects of the present disclosure will be revealed and clarified by referring to the embodiments described below.

[0091] Herein, embodiments of the present invention will be described simply as examples, with reference to the attached drawings. [Brief explanation of the drawing]

[0092] [Figure 1] This is a perspective view of a syringe suitable for use in embodiments of the present disclosure, with the plunger rod shown in its initial position. [Figure 2] Figure 1 is a side view of the syringe. [Figure 3] Figures 1 and 2 are side views of the syringe after the plunger rod has been moved from its initial position. [Figure 4] This is a perspective view of a dose divider according to an embodiment of the present disclosure when the dose divider is in the first configuration. [Figure 5] This is a top view of the dose divider shown in Figure 4, which is part of the first configuration. [Figure 6] This is a top view of the dose divider in Figure 4, which is part of the second configuration. [Figure 7] The second configuration consists of perspective views of the dose dividers shown in Figures 4-6, which are attached to the syringes shown in Figures 1-3. [Figure 8] This is a perspective view of the dose divider in the first configuration shown in Figure 7, which is attached to the plunger rod of a syringe. [Figure 9] Figure 8 is a side view of the dose divider and syringe. [Figure 10] Figures 8 and 9 are cross-sectional side views of the dose divider and syringe, with the dose divider connected to the syringe and the plunger rod in its initial position. [Figure 11] Figure 10 is a cross-sectional side view of the dose divider and syringe, with the plunger rod in the intermediate position. [Figure 12] Figure 11 is a cross-sectional side view of the dose divider and syringe with the plunger rod in the end position. [Figure 13] This is a flowchart illustrating the usage of a dose divider and syringe. [Modes for carrying out the invention]

[0093] Aspects of this disclosure provide an improved dose divider, also known as a dose divider clip. This dose divider may be easier for the user to control, for example, when removing or attaching the dose divider to the plunger rod of a syringe. This dose divider may be easier to control, especially for users with reduced manual dexterity. This dose divider may be easier to reuse, for example, it may allow repeated attachment and detachment to the plunger rod of a syringe. This dose divider may be coupled to many different types of plunger rods having different cross-sections. This dose divider may be flexible in use, for example, it may be mounted at many different positions along the plunger rod. This dose divider may be easier to reposition on the plunger rod, for example, from a position near the proximal end of the plunger rod to a position near the distal end of the plunger rod.

[0094] Figures 1-3 show syringes 10 suitable for use in various embodiments of the present disclosure. Syringe 10 has a proximal end P and a distal end D, is generally elongated, and has a central axis XX. Syringe 10 includes a drug container 11 (hereinafter, "container 11"), an actuator 12 in the form of a plunger rod or piston rod 12, and a finger grip 13 optionally fixed to the proximal end of container 11. Container 11 is elongated and includes an outer side wall 14 defining a drug chamber 15 for containing the drug. Container 11 is open at the proximal end P and includes an outlet 16 at the distal end D opposite the proximal end of container 11. The term "distal" refers to a location relatively close to the outlet 16 from which the drug is delivered during use, while the term "proximal" refers to a location relatively far from the outlet 16. The distal region of the plunger rod 12, which is received within the container 11, is in close contact with the inner wall of the container 11, which can prevent the drug from flowing out from the open proximal end P of the container 11. The proximal end of the plunger rod 12 includes an end face 20, which the user presses during use to dispense the drug (described in more detail below). The end face 20 extends beyond the plunger rod 12 in at least one direction perpendicular to the axis XX. Therefore, the distal face 21 of the end face 20, which is opposite the proximal end of the container 11, may eventually come into contact with the proximal end of the container 11 when the plunger rod 12 is pushed into the chamber 15, preventing the plunger rod 12 from moving further into the chamber 15.

[0095] The outlet 16 includes a narrow section leading to the nozzle of the container 11. An atomizer 17 may be provided at the outlet 16. The atomizer 17 and / or the outlet 16 may include a connector, such as a Luer lock, for tightly connecting the atomizer 17 to the outlet 16. In some examples, the atomizer 17 may be formed to facilitate insertion of the outlet into an opening to which the drug is to be delivered, such as a nostril. The atomizer 17 may consist of a drug passage configured to spray the liquid drug through the outlet 16 and through the atomizer 17.

[0096] The atomizer 17 may have a conical shape as shown in Figures 1 and 2, with a tapered outer surface, and its width decreasing from the proximal end (where the atomizer 17 is connected to the outlet 16) to the distal end (where the atomizer 17 is first inserted into the hole). The conical shape of the atomizer 17 may allow for more consistent and accurate direction of the sprayed drug toward a desired target when inserted into a hole such as a nostril. For example, when the atomizer 17 is inserted into the nasal cavity through a nasal valve, the drug may be more consistently and accurately directed toward the upper part of the patient's nasal cavity.

[0097] Atomizer 17 has an average droplet size of approximately 10-120 μm. v50 It can be configured to deliver. Average droplet size D delivered to each nostril v50 The size can be approximately 10-120 μm, approximately 30-110 μm, approximately 50-110 μm, approximately 70-110 μm, or approximately 80-110 μm.

[0098] The atomizer 17 may have a tip diameter of approximately 4 mm to 5 mm at its distal end, for example, approximately 4.3 mm. The atomizer 17 may have a dead space of less than approximately 0.3 mL, for example, less than approximately 0.2 mL. In some examples, the dead space may be approximately 0.15 mL.

[0099] The atomizer 17 may be formed from medical-grade polycarbonate material. Other suitable materials may also be considered.

[0100] The atomizer 17 may conform to ISO-594 (using a suitable Luer lock) for connecting the syringe 10 to the atomizer 17, and the syringe 10 may also conform to ISO-594 (using a suitable Luer lock).

[0101] The container 11 described herein may be any suitable shape or configuration, such as a hollow tube or other body. In some examples, the piston 18 may be located within the drug chamber 15 in close contact with the inner wall of the container 11. In such a configuration, the piston 18 may be attached to the distal end of the plunger rod 12 (see Figure 2), thus eliminating the need to make the plunger rod 12 in close contact with the inner wall of the container 11.

[0102] During use, the drug 19 is supplied into the drug chamber 15 and remains within the chamber 15 by a seal of the plunger rod 12 and / or piston 18 at the proximal end of the chamber 15 and a narrow outlet 16 at the distal end of the chamber 15, which is provided with a cap, valve, temporarily breakable seal, or other opening / closing mechanism. Alternatively, the narrow outlet 16 alone may prevent the drug 19 from leaking out of the distal end of the chamber 15. The drug 19 may be discharged from the chamber 15 in one or more doses by moving the plunger rod 12 linearly distally into the chamber 15, thereby reducing the volume of the chamber 15 between the outlet 16 and the plunger rod 12 and / or piston 18, and pushing the drug 19 out of the outlet 16 (and the atomizer 17, if present).

[0103] Figure 2 is a cross-sectional side view of the syringe 10 of Figure 1 in its initial state, showing the plunger rod 12 in its initial position relative to the container 11. The syringe 10 in Figure 2 may be in a state before drug delivery, with the chamber 15 containing drug 19 equivalent to one or more doses to be delivered, and the distal surface 21 of the end face 20 being at a distance L1 from the proximal end of the container 11 along the central axis XX.

[0104] During use, the user can apply force to the plunger rod 12 via the end face 20 in the direction from the proximal end to the distal end of the container 11, thereby translating the plunger rod 12 relative to the container 11. By translating the plunger rod 12 toward the distal end of the container 11 and further into the chamber 15 in this manner, the plunger rod 12 and / or piston 18 apply force to the drug 19 in the chamber 15, thereby causing at least a portion of the drug 19 to be discharged from the chamber 15 through the outlet 16 and an optional atomizer 17.

[0105] Figure 3 is a cross-sectional side view of the syringe 10 of Figure 2 in its final state after the plunger rod 12 has been moved from its initial position relative to the container 11 to its final position relative to the container 11, and at least a portion of the drug 19 has been discharged from the chamber 15 during the process. Figure 3 shows that some of the drug 19 still remains in the chamber 15, but in other examples, substantially all of the drug 19 may have been discharged from the chamber 15.

[0106] Figure 3 shows that the plunger rod 12 and end face 20 are moved parallel to the central axis XX of the syringe 10 by a distance equal to L1, so that the distal surface 21 of the end face 20 abuts against the proximal end of the container 11, thereby preventing the plunger rod 12 from moving further into the container 11 and chamber 15. However, in other examples, further translational movement of the plunger rod 12 into the container 11 and chamber 15 can be prevented if the distal end of the plunger rod 12 or piston 18 abuts against the distal end of the chamber 15, which can occur even if the distal surface 21 of the end face 20 does not abut against the proximal end of the container 11.

[0107] The amount of drug 19 dispensed from syringe 10 during the transition between the initial state shown in Figure 2 and the final state shown in Figure 3 may be equivalent to a dose of the drug. However, in other examples, the amount of drug 19 dispensed may correspond to two doses, or even three or more doses. In such scenarios, the user of syringe 10 may want to dispense less than the total dose of the drug contained in syringe 10 during a single drug delivery procedure. For example, the user may want to dispense one dose of drug 19 from multiple doses of drug 19 contained in chamber 15. Therefore, the user may move the plunger rod 12 toward container 11 within a first range of motion over a specific distance, resulting in the dispensing of an amount of drug 19 equivalent to one dose (or different required doses) from syringe 10, after which further movement of the plunger rod 12 is stopped. As an example, this specific distance may be less than L1 shown in Figure 2. The user may then, at a later point, perhaps after moving the syringe 10 to a different location on the patient, move the plunger rod 12 over a different distance in a second range of motion toward the distal end of the container 11 to dispense one or more subsequent doses of the drug 19. Thus, the syringe 10 may be used to dispense two or more distinct doses of the drug 19.

[0108] For example, if the amount of drug 19 dispensed from syringe 10 during the transition between the initial state shown in Figure 2 and the final state shown in Figure 3 is equal to two doses of drug 19, the user may move the plunger rod 12 a distance equivalent to half the length of L1 to dispense the first dose, and then move the plunger rod 12 again a distance equivalent to half the length of L1 to dispense the second dose. If syringe 10 is used for intranasal vaccine administration, the user may dispense the first dose through the patient's first nostril and the second dose through the patient's second nostril.

[0109] It may be difficult for the user to accurately divide the dose of drug 19 by moving the plunger rod 12 of syringe 10 by a predetermined distance, which is part of the total range of motion of the plunger rod 12. For example, it may be difficult to accurately determine how far to move the plunger rod 12. As a result, accidental under-dosing or over-dosing may occur, which could lead to adverse effects on the patient and / or waste of drug.

[0110] Figures 4-6 show a dose divider 30 (dose divider element or dose divider clip) according to one or more embodiments of the present disclosure, which can be used to divide the dose of drug 19 contained in a syringe 10. The dose divider 30 is configured to be detachably coupled to the plunger rod 12 of the syringe 10, which may allow the user to more easily and accurately dispense two or more individual doses of drug 19 from the syringe 10. The syringe 10 may be one of those described above with respect to Figures 1-3, but it should be noted that the syringes 10 shown in Figures 1-3 are shown as examples, and the dose divider 30 can be used with any suitable syringe 10.

[0111] Figure 4 shows a perspective view of the dose divider 30, and Figures 5 and 6 show top views of the dose divider 30 of Figure 4. Figure 5 shows the dose divider 30 in the first configuration, and Figure 6 shows the dose divider 30 in the second configuration, which will be explained later.

[0112] As shown in Figures 4 and 5, the dose divider 30 is generally elongated and has a front end and a rear end with respect to its central axis YY, the front end being near the upper opening 58 in Figure 5 and the rear end being near the lower rear parts 45a and 45b in Figure 5.

[0113] The dose divider 30 includes a first arm 41 and a second arm 42 positioned on each side of the central axis YY. The first arm 41 and the second arm 42 are spaced apart from each other and positioned opposite each other, and each may extend substantially parallel to the central axis YY.

[0114] The first arm 41 includes a front portion 44a located at the front end of the first arm 41 and a rear portion 45a located at the rear end of the first arm 41. Similarly, the second arm 42 includes a front portion 44b located at the front end of the second arm 42 and a rear portion 45b located at the rear end of the first arm 41. The term "front" refers to a position relatively close to the front end of the dose divider 30, and the term "rear" refers to a position relatively far from the front end.

[0115] The front portion 44a of the first arm 41 is positioned opposite the front portion 44b of the second arm 42, so that the front portions 44a and 44b are on opposite sides of axis YY, and the inner surface 46a of the front portion 44a of the first arm 41 faces the inner surface 46b of the front portion 44b of the second arm 42. The front portions 44a of the first arm 41 and 44b of the second arm 42 form a channel 47 between them for receiving the plunger rod 12 of the syringe 10, as will be discussed later. The channel 47 is formed between the inner surfaces 46a and 46b.

[0116] The rear portion 45a of the first arm 41 is positioned on the opposite side of the rear portion 45b of the second arm 42, so that the rear portions 45a and 45b are on opposite sides of axis YY, and the inner surface 48a of the rear portion 45a of the first arm 41 faces the inner surface 48b of the rear portion 45b of the second arm 42.

[0117] The first arm 41 and the second arm 42 are pivotably connected by an elastic hinge, and the first arm 41 can pivot with respect to the second arm 42 via the elastic hinge. An elastic hinge 49 pivotably connects the first arm 41 and the second arm 42, thereby allowing the dose divider 30 to move reversibly between a first configuration in which the first arm 41 is in a first position with respect to the second arm 42 and a second configuration in which the first arm 41 is in a second position with respect to the second arm 42. The dose divider 30 can be moved from the first configuration to the second configuration by the user by bringing the rear parts 45a, 45b closer together, and this movement causes the first arm 41 to pivot with respect to the second arm 42 using the elastic hinge 49, thereby moving the front parts 44a, 44b further apart. The elasticity of the elastic hinge 49 biases the dose divider from the second configuration to the first configuration, thereby releasing the force that was bringing the rear parts 45a and 45b closer together, causing them to move apart, the first arm 41 to pivot in the opposite direction relative to the second arm 42, and the front parts 44a and 44b to move closer together. The first and second configurations will be described in more detail later.

[0118] The elastic hinge 49 may be coupled at one end to the first arm 41 at a position between the front portion 44a and the rear portion 45a of the first arm 41, and at the other end to the second arm 42 at a position between the front portion 44b and the rear portion 45b of the second arm 42.

[0119] The elastic hinge 49 may be arched, as shown in Figures 4 and 5. In particular, the elastic hinge 49 may be curved in a plane parallel to the axis YY, with the apex of the curve positioned toward the rear of the elastic hinge 49. This allows the elastic hinge 49 to provide good elastic properties while remaining compact, and thus a compact dose divider 30 can be obtained.

[0120] Figure 4 shows an elastic hinge 49 including a pair of substantially parallel straight sections 50a, 50b on each side of axis YY, facing each other and spaced apart from each other. The straight sections 50a, 50b extend in a direction substantially parallel to axis YY. The first straight section 50a of the pair of straight sections 50a, 50b is coupled at its front end to the first arm 41 at a position between the front 44a and rear 45a of the first arm 41. The second straight section 50b of the two straight sections 50a, 50b is coupled at its front end to the second arm 42 at a position between the front 44b and rear 45b of the second arm 42. Figure 5 shows the first straight section 50a and the second straight section 50b, each of which curves away from the central axis YY closer to its respective front end, and these are adjacent to the locations where they are coupled to the first arm 41 and the second arm 42, respectively.

[0121] The elastic hinge 49 shown in Figure 5 further includes a curved portion 51 that connects the rear ends of the straight portions 50a and 50b. The curved portion 51 curves in the opposite direction to the front end of the dose divider 30, and the apex of the curved portion is located at the rear of the elastic hinge 49.

[0122] The elastic hinge 49 may be a living hinge formed integrally with the first arm 41 and the second arm 42. This results in a simple hinge that is easy to manufacture and eliminates the need for more complex elements such as metal springs and bearings. In some examples, the elastic hinge 49 may be formed from a polymer such as polylactic acid (PLA).

[0123] The rear portion 45a of the first arm 41 and the rear portion 45b of the second arm 42 may each have grip configurations 52a, 52b on their respective outer surfaces 53a, 53b, positioned for the user to grip when moving the dose divider 30 between the first and second configurations, or when attaching and detaching the dose divider 30 to the plunger rod 12. The grip configurations 52a, 52b provide an improved gripping surface for the user to hold the rear portions 45a, 45b, for example, by increasing the friction between the rear portions 45a, 45b and the user's fingers.

[0124] Figures 4 and 5 show grip configurations 52a and 52b, each containing multiple protrusions such as ridges 54a-f, 54a'f'. Each ridge 54a-f, 54a'f' extends along the outer surfaces 53a, 53b of their respective rear portions 45a, 45b in a direction substantially perpendicular to the central axis YY, and the ridges 54a-f, 54a'f' are spaced apart from each other in a direction substantially parallel to the central axis YY. Such a configuration may provide improved friction and grip for the user to connect and disconnect the dose divider 30 from the syringe 10, as will be discussed later. Figures 4 and 5 show grip configurations 52a and 52b, each containing six ridges 54a-f, 54a'f', but in other examples, any number of ridges 54a-f, 54a'f' can be used for each grip configuration 52a and 52b. In other examples, one or both grip configurations 52a, 52b may include features different from the raised portions 54a~f, 54a'f', which are, for example, raised portions, grooves, adhesive surfaces and / or high-friction surfaces such as rubber. In some examples, the grip configurations 52a, 52b may be provided on only one of the rear portions 45a, 45b.

[0125] As described above, the front portions 44a and 44b of the dose divider 30 form an elongated channel 47 for receiving the plunger rod 12 when the dose divider 30 is coupled to the plunger rod 12. The channel 47 extends from the top surface 55 of the dose divider 30 to the bottom surface 56 of the dose divider 30 and is open at both ends so that the plunger rod 12 can be received in the channel 47, the dose divider 30 can slide along the plunger rod 12 and the plunger rod 12 can translate within the channel 47.

[0126] The top surface 55 is formed from the top surfaces of the front portions 44a and 44b surrounding one end of the channel 47, and the bottom surface 56 is formed from the bottom surfaces of the front portions 44a and 44b surrounding the other end of the channel 47. The distance L3 between the top surface 55 and the bottom surface 56, which corresponds to the height of the dose divider 30, may in some examples be a dimension L3 of 16 mm to 19 mm, for example, 17 mm to 18 mm, or more specifically, a dimension L3 equal to 17.5 mm.

[0127] The height of the dose divider 30 corresponds to the volume of the dose to be dispensed, as described elsewhere in this application. For example, a dose divider 30 having a dimension L3 equal to 17.5 mm may correspond to the dispensing of a 0.1 mL dose of drug. In other examples, a dose divider 30 having a dimension L3 equal to 35.0 mm may correspond to the dispensing of a 0.2 mL dose of drug, and a dose divider 30 having a dimension L3 equal to 26.25 mm may correspond to the dispensing of a 0.15 mL dose of drug. However, other values ​​for dimension L2, dose volume, and the ratio of dimension L2 to dose volume may also be considered. For example, a dose divider 30 having a dimension L3 equal to 20.0 mm may correspond to the dispensing of a 0.2 mL dose of drug, or a dose divider 30 having a dimension L3 equal to 10.0 mm may correspond to the dispensing of a 0.2 mL dose of drug.

[0128] In some examples, different dose dividers 30 may have different colors corresponding to the dose volume they can dispense (i.e., the color corresponds to the dimension L3 of the dose divider 30). For example, a red dose divider 30 (or at least a portion of the dose divider 30 is colored red) may indicate that the dose divider 30 has a dimension L3 equal to 17.5 mm and therefore corresponds to the dispensing of a dose of 0.1 mL, and a green dose divider 30 (or at least a portion of the dose divider 30 is colored green) may indicate that the dose divider 30 has a dimension L3 equal to 35.0 mm and therefore corresponds to the dispensing of a dose of 0.2 mL. The colors, dimensions L3 and dose volumes are given as examples, and it is assumed that other colors, L3 dimensions, or dose volumes, and / or combinations thereof may be used.

[0129] In some examples, dose dividers 30 corresponding to different dose volumes may be distinguished by means other than (or in addition to) color, for example, by marking the dose divider 30 with a mark indicating the dose volume, or by forming at least a portion of the dose divider 30 from a specific material and / or having specific surface properties that indicate the dose volume.

[0130] The channel 47 may have a substantially constant cross-section along its length. The cross-section of the channel 47 may closely correspond to the cross-section of the plunger rod 12, thereby ensuring that the plunger rod 12 is firmly received in the channel 47 when the dose divider 30 is coupled to the plunger rod 12. However, the cross-section of the channel 47 may be slightly larger in each dimension than the cross-section of the plunger rod 12 so that the plunger rod 12 can slide freely within the channel 47. Figures 4 and 5 show a channel having a star-shaped cross-section formed from a series of ridges and grooves formed along the length of the channel 47, but it is also conceivable that the channel 47 may be provided with a different cross-section instead. The channel 47 may have a specific shape configured to receive a particular outer shape of the plunger rod 12, thereby ensuring that the plunger rod 12 is tightly received within the channel 47.

[0131] The front portions 44a and 44b of the first and second arms 41 and 42 are separated by a gap at their front ends to form an opening 58. The opening 58 is located at the front end of the dose divider 30, and the channel 47 is located at the rear of the opening 58. The opening 58 is configured to receive the plunger rod 12 while the dose divider 30 is coupled to the plunger rod 12. The opening 58 connects to the side of the channel 47, and the plunger rod 12 can enter the channel 57 through the opening 58 when the dose divider 30 is coupled to the plunger rod 12.

[0132] Each of the front sections 44a, 44b may include lips 57a, 57b formed on the inner surfaces 48a, 48b of each front section 44a, 44b at the front end of the front section 44a, 44b. Each lip 57a, 57b extends elongated along the direction from the top surface 55 to the bottom surface 56 of the dose divider 30, parallel to the longitudinal axis of the channel 47. The rear side of each lip 57a, 57b forms part of the wall of the channel 47. The lips 57a, 57b form an opening 58 between them.

[0133] The opening 58 is elongated and extends parallel to the longitudinal axis of the lips 57a, 57b and the channel 47. The opening has a width W1 between the lips 57a, 57b, representing the minimum distance between the lips 57a, 57b. The dose divider 30 is configured such that, when the dose divider 30 is coupled to the plunger rod 12 as described later, the lips 57a, 57b prevent the plunger rod 12 from being removed from the channel 47 in a direction toward the front of the dose divider 30 (i.e., perpendicular to axis XX and parallel to axis YY). This is achieved by shaping the dose divider 30 such that, when the dose divider 30 is coupled to the plunger rod 12, the width W1 of the opening 58 is smaller than the corresponding width of the plunger rod 12, as will be described later in relation to Figure 6. The width W1 of the opening 58 changes as the dose divider 30 moves from the first configuration shown in Figure 5 to the second configuration shown in Figure 6, which is due to the first arm 41 pivoting around the elastic hinge 49 with respect to the second arm 42.

[0134] The dose divider 30 may also include first and second guide surfaces 60, 61. The first and second guide surfaces 60, 61 are configured to guide the plunger rod 12 into the channel 47 through the opening 58 while the dose divider 30 is attached to the plunger rod 12.

[0135] Figures 4 and 5 show the first guide surface 60 formed at the front end of the front portion 44a of the first arm 41 and the second guide surface 61 formed at the front end of the front portion 44b of the second arm 42. The first guide surface 60 and the second guide surface 61 are inclined relative to each other to guide the plunger rod 12 toward the opening 58 when the dose divider 30 is coupled to the plunger rod 12. The first guide surface 60 and the second guide surface 61 are angled such that they approach each other as one moves along the axis YY from the front end to the rear end of the dose divider 30. As will be described later, the guide surfaces can be used to assist in guiding the plunger rod 12 into the opening 58, so that the user does not need to apply substantial pressure or use high precision.

[0136] The dose divider 30 may include a block feature 62 positioned to prevent the plunger rod 12 from moving toward the rear of the dose divider 30 when the plunger rod 12 is positioned within the channel 47. Figures 4 and 5 show a block feature 62 including a first block projection 63 and a second block projection 64, both positioned toward the rear of the channel 47, between the channel 47 and the elastic hinge 49. The first block projection 63 is located on the elastic hinge 49, on the first linear section 50a of the elastic hinge 49, and projecting toward the axis YY in a direction substantially perpendicular to the axis YY. The second block projection 64 is also located on the elastic hinge 49, this time on the second linear section 50b of the elastic hinge 49, and likewise projecting toward the axis YY in a direction substantially perpendicular to the axis YY, but in the opposite direction to the first block projection 63. The first block projection 63 and the second block projection 64 are substantially aligned with each other in a plane parallel to axis YY and separated by a distance W2. Figures 4 and 5 show that each of the first block projection 63 and the second block projection 64 takes the form of a ridge extending perpendicular to the channel 47 along its longitudinal axis.

[0137] The first block projection 63 and the second block projection 64 may be sized such that the distance W2 is small enough to prevent the plunger rod 12 from exiting the channel 47 and moving toward the rear of the dose divider 30 when the dose divider 30 is in its first configuration. As discussed elsewhere, when the dose divider 30 is moved from its first configuration to its second configuration, the first block projection 63 and the second block projection 64 move apart from each other, increasing the distance W2. Therefore, the first block projection 63 and the second block projection 64 may also be sized such that the distance W2 remains small enough to prevent the plunger rod 12 from exiting the channel 47 and moving toward the rear of the dose divider 30 when the dose divider 30 is in its second configuration.

[0138] The dose divider 30 may further include a stop configuration 66 for restricting the relative movement of the rear portion 45a of the first arm 41 and the rear portion 45b of the second arm 42. Figures 4 and 5 show the stop configuration 66 positioned on the inner surfaces 48a, 48b of the rear portions 45a, 45b of the first arm 41 and the second arm 42. In particular, the stop configuration 66 is shown to include a first projection 67 extending from the inner surface 48a of the rear portion 45a of the first arm 41 and a second projection 68 extending from the inner surface 48b of the rear portion 45b of the second arm 42. The first projection 67 and the second projection 68 are each positioned approximately midway along the length of their respective rear portions 45a, 45b, but other positions along the length of their respective rear portions 45a, 45b may also be used instead.

[0139] The first projection 67 and the second projection 68 each extend substantially in opposite directions toward the central axis YY and are separated by a shortest distance W3. When the dose divider 30 is moved from the first configuration to the second configuration by bringing the rear portions 45a and 45b of the first arm 41 and the second arm 42 closer together, the first projection 67 and the second projection 68 move toward each other, the distance W3 between them decreases, and they are eventually positioned so that the first projection 67 contacts the second projection 68 and the rear portions 45a and 45b do not move any further (i.e., the point where W3=0). This is illustrated by the second configuration of the dose divider 30 shown in Figure 6.

[0140] By adjusting the dimensions of the stop configuration 66, such as the distance the first projection 67 and / or the second projection 68 extend from their respective rear portions 45a and 45b, the amount by which the rear portions 45a and 45b can be brought closer together is adjusted, along with the amount by which the front portions 44a and 44b can be moved apart. Thus, by providing the stop configuration 66 in the dose divider 30, a simple means can be provided to adjust the amount by which the front portions 44a and 44b can be moved apart, and therefore the amount by which the width W1 of the opening 58 can be changed, which means that the dose divider 30 can be easily adjusted to receive plunger rods 12 of different dimensions. By providing the stop configuration 66 for limiting the relative movement between the rear portions 45a and 45b, excessive movement of the rear portions 45a and 45b, which could break or otherwise damage the first and / or second arms 41, 42 and / or elastic hinges 49, can also be prevented.

[0141] Figures 4 and 5 both show a first projection 67 and / or a second projection 68 extending as ridges perpendicular to the axis YY from near the top of the dose divider 30 to near the bottom of the dose divider 30, along the inner surfaces 48a and 48b of the rear portions 45a and 45b. However, it is conceivable that the first projection 67 and / or the second projection 68 may take a different form.

[0142] In some examples, the stop configuration 66 may be located on only one of the first arm 41 and the second arm 42. For example, the rear portion 45a of the first arm 41 may include a first projection 67 extending from the inner surface 48a of the rear portion 45a of the first arm 41, while there is no corresponding second projection 68 on the second arm 42. In this case, the first projection 67 would be configured to contact the inner surface 48b of the rear portion 45b of the second arm 42 when the rear portions 45a and 45b are brought close to each other, thereby preventing the rear portions 45a and 45b from moving further toward each other.

[0143] Figures 4 and 5 show a first projection 67 having a groove 69 configured to receive at least a portion of the second projection 68. The groove 69 is formed on the surface of the first projection 67 that abuts against the second projection 68 when the rear portions 45a and 45b are brought close to each other. The groove 69 increases the length of the first projection 67 from the top to the bottom of the first projection 67. By providing the groove 69 on the first projection 67, when the first projection 67 and the second projection 68 come into contact, the second projection 68 is reliably guided into the groove 69 and firmly received, reducing the possibility of misalignment between the first projection 67 and the second projection 68, which could lead to the first projection 67 and the second projection 68 not coming into contact.

[0144] The dose divider 30 may be formed from a single piece of material. In some examples, the dose divider 30 may be formed entirely or in part from a polymer such as polylactic acid (PLA). Since PLA is biodegradable and compostable, forming the dose divider 30 from PLA may reduce the environmental impact in general waste streams. Alternatively, other suitable polymers or materials may be used.

[0145] A dose divider 30 made from a single material such as a single polymer can be formed using a molding process such as an injection molding process that uses a single or multiple cavity mold.

[0146] In some cases, the dose divider 30 may be formed from two or more materials. For example, one or more of the grip components 52a, 52b may be formed from a different material than the rest of the dose divider 30. For example, one or more of the grip components 52a, 52b may be formed from a plastic that is softer and / or more flexible than the plastic used to form the rest of the dose divider 30, which can maintain the overall structural integrity of the dose divider 30 while improving user comfort when the user grips the dose divider 30. A dose divider 30 made from multiple materials, such as multiple polymers, can be formed using a molding process such as an injection molding process. Such a dose divider 30 may be formed using overmolding or insert molding.

[0147] In some cases, the dose divider 30 may be formed in whole or in part by an additive manufacturing process (also known as three-dimensional (3D) printing).

[0148] Figures 4 and 5 show the dose divider 30 in its first configuration before the process of attaching it to the plunger rod 12. The dose divider 30 is movable between the first and second configurations, and the second configuration of the dose divider is shown in Figure 6.

[0149] To connect the dose divider 30 to the plunger rod 12, the user moves the dose divider 30 from a first configuration (for example, shown in Figure 5) to a second configuration (for example, shown in Figure 6) by applying compressive force to the outer surfaces 53a, 53b of the rear portions 45a, 45b of the first arm 41 and the second arm 42, as shown in Figures 6 and 7, thereby bringing the rear portions 45a, 45b closer together.

[0150] As shown in Figures 6 and 7, when the user brings the rear sections 45a and 45b closer together by squeezing them between the thumb and other fingers, the elastic hinge 49 causes the first arm 41 to pivot relative to the second arm 42. As the rear sections 45a and 45b pivot toward each other, the front sections 44a and 44b move toward each other. As a result, the lips 57a and 57b move toward each other, increasing the width W1 of the opening 58. The first and second guide surfaces 60 and 61 also move toward each other, as do the inner surfaces 46a and 46b of the front sections 44a and 44b that form the channel 47. The shape of the channel 47 (e.g., cross-section) changes as the user moves the dose divider 30 from the first configuration (e.g., shown in Figure 5) to the second configuration (e.g., shown in Figure 6) (e.g., the width increases). The first block projection 63 and the second block projection 64 also move toward each other, increasing the distance W2. The joint movement of the rear sections 45a and 45b is ultimately restricted by the stop configuration 66, which causes the first projection 67 and the second projection 68 to come into contact, as shown in Figure 6, thereby preventing further relative movement.

[0151] When the dose divider 30 is in the second configuration, it is configured to receive the plunger rod 12 into the channel 47 through an opening 48 formed between the front portion 44a of the first arm 41 and the front portion 44b of the second arm 42. That is, the user can move the plunger rod 12 into the channel 47 through the opening 48. When the dose divider 30 is in this second configuration, the channel 47 has a shape (i.e. cross-section) configured to receive a specific outer shape (i.e. cross-section) of the plunger rod 12. The shape of the channel 47 is larger than the shape of the plunger rod 12, allowing the plunger rod 12 to be inserted into the channel 47.

[0152] The user rotates the first arm 41 with respect to the second arm 42 so that the dose divider 30 is in a second configuration, and the opening 48 is wide enough to receive the plunger rod 12 (i.e., the width W1 is sufficient to accommodate the width of the plunger rod 12). At this time, the user can bring the plunger rod 12 closer to the front end of the dose divider 30, so that the longitudinal axis XX of the plunger rod 12 is substantially parallel to the longitudinal axis of the channel 47 and the opening 58. The user moves the plunger rod 12 from the opening 58 into the channel 47, as shown in Figure 7, so that the plunger rod 12 is positioned inside the channel and coaxial with the channel 47.

[0153] The plunger rod 12 may come into contact with one or both of the first and second guide surfaces 60, 61 before entering the opening 58. When the user moves the plunger rod 12 toward the opening 58 of the dose divider 30, the reaction force between one or both of the guide surfaces 60, 61 and the plunger rod 12 causes the plunger rod 12 to align with the opening 58 and is ultimately guided into the opening 58. Thus, the guide surfaces 60, 61 provide a greater tolerance for coupling the dose divider 30 with the plunger rod 12, and as a result, the user is not required to be precise in aligning the plunger rod 12 with the dose divider 30.

[0154] When the dose divider 30 is in the second configuration, the width W1 of the opening is wider than the width of the plunger rod 12, allowing the plunger rod 12 to be freely inserted through the opening 58. However, in other examples, the width W1 of the opening 58 may be slightly smaller than the width of the plunger rod 12. In such examples, the user applies force to the plunger rod 12 toward the opening 58 by bringing it close to the opening 58 as before. This force, transmitted to the guide surfaces 60, 61 or lips 57a, 57b, causes the front portions 44a, 44b of the first and second arms 41, 42 to separate from each other by the flexibility of the first and / or second arms 41, 42, resulting in an increase in the width W1 of the opening 58. As the user continues to apply force, the opening 58 widens until the plunger rod 12 can eventually pass through the channel 47 and enter it. The width W1 of the opening 58 when the dose divider 30 is in the second configuration can be selected by adjusting the dimensions of the stop configuration 66, as described above.

[0155] As shown in Figure 6, when the dose divider 30 is moved from the first configuration to the second configuration, the first block projection 63 and the second block projection 64 move apart from each other, and the distance W2 between them increases. However, the first block projection 63 and the second block projection 64 can be sized such that, regardless of whether the dose divider 30 is in the first or second configuration, the distance W2 between the first block projection 63 and the second block projection 64 remains small enough to prevent the plunger rod 12 from moving from the channel 47 toward the rear of the dose divider 30, as shown in Figures 7 and 8.

[0156] When the plunger rod 12 is received within the channel 47 of the dose divider 30, as shown in Figure 8, the user can release the first arm 41 and the second arm 42, at which point the dose divider 30 returns from the second configuration to the first configuration by the elasticity of the elastic hinge 49, with the front parts 44a and 44b moving closer together and the rear parts 45a and 45b moving apart. The shape (e.g., cross-section) of the channel 47 changes (e.g., width decreases) when the user releases the dose divider 30 from the second configuration to the first configuration, so that the plunger rod 12 is snugly received within the channel 47. When the dose divider 30 is in the first configuration, the channel 47 has a shape (e.g., cross-section) configured to receive a specific outer shape (e.g., cross-section) of the plunger rod 12. That is, the shape of the channel 47 closely corresponds to the shape of the plunger rod 12, so that the plunger rod 12 is securely received within the channel 47.

[0157] The syringe 10 and dose divider 30 shown in Figure 8 may be collectively referred to as a drug delivery device 70. The drug delivery device 70 may be a nasal spray administration device.

[0158] Figure 7 is a perspective view of the proximal end of syringe 10, such as the dose divider 30 in Figures 4-6 and syringe 10 as already described in Figures 1-3. Figure 7 shows the dose divider 30 in a second configuration, coupled to the plunger rod 12 of syringe 10 in the manner described above. The plunger rod 12 is inserted through the opening 58 of the dose divider 30 and received within the channel 47, and the plunger rod 12 is substantially coaxial with the channel 47. The cross-section of the channel 47 when the dose divider 30 is in the second configuration is wider than the cross-section of the channel 47 when the dose divider 30 is in the first configuration, because the front portions 44a and 44b of the first arm 41 and the second arm 42 are separated from each other.

[0159] To complete the coupling of the dose divider 30 to the plunger rod 12, the user releases the rear portions 45a, 45b of the first arm 41 and the second arm 42, as shown in Figure 8. Due to the elasticity of the elastic hinge 49 connecting the first arm 41 and the second arm 42, the dose divider 30 moves back to its first configuration, and the front portions 44a, 44b of the first arm 41 and the second arm 42 move closer together again. This reduces the cross-section of the channel 47, allowing the channel 47 to surround the plunger rod 12 more tightly than before. The lips 57a, 57b move closer together, narrowing the width W1 of the opening 58 and preventing the plunger rod 12 from moving away from the dose divider 30 again. The drug delivery device 70 is now ready to deliver the first dose of the drug 19.

[0160] Figure 9 shows the dose divider 30 and syringe 10 from Figure 8 from a side view, with the dose divider 30 coupled to the plunger rod 12 of the syringe 10. Figure 9 shows that the dose divider 30 is coupled to the distal end of the portion of the plunger rod 12 that extends outside the container 11, so that the dose divider 30 abuts against the proximal end of the container 11, and the distal surface 21 of the end face 20 is separated from the dose divider 30. However, in other examples, the dose divider 30 may be coupled to another portion of the plunger rod 12 that extends outside the container 11, for example, closer to the end face 20, so as not to abut against the proximal end of the container 11.

[0161] The operation of the dose divider 30 will now be described with reference to Figures 10-12. This operation will be described in relation to its use with a nasal drug administration syringe 10, i.e., a syringe 10 for delivering medication into the patient's nasal cavity. However, this concept is not intended to be limited to use with a nasal drug administration syringe 10, and may be equally applicable to various other forms of syringes 10 in which medication is intended to be delivered in two or more separate doses.

[0162] Regarding the nasal drug administration syringe 10, the volume of drug, such as vaccine, in the syringe 10 often needs to be delivered to each nostril of the patient, and often the volume of drug is divided equally into doses for each nostril. When using such a syringe 10, the syringe 10 starts from the initial position shown in Figure 10. The distal surface 21 of the end face 20 of the plunger rod 12 is positioned parallel to the central axis XX at a distance L2 from the proximal end of the container 11. The dose divider 30 has a distance L3 between its top surface 55 and bottom surface 56. Length L4 corresponds to L2-L3. This length L4 is the length of the plunger rod 12, excluding the distance between the distal surface 21 of the end face 20 and the proximal end of the container 11, and the distance between the top surface 55 and bottom surface 56 of the dose divider 30. L4 corresponds to the maximum distance the plunger rod 12 can be moved toward the container 11 while the dose divider 30 is coupled to the plunger rod 12, and therefore corresponds to the maximum amount of drug 19 that can be dispensed during such movement. This amount of drug 19 may correspond to a first dose of drug 19.

[0163] Figure 10 shows the distance L4, which is the continuous length between the distal surface 21 of the end face 20 of the plunger rod 12 and the proximal surface of the dose divider 30. However, in cases where the dose divider 30 does not initially contact the proximal end of the container 11, L4 may include both the length between the distal surface 21 of the end face 20 and the upper surface 55 of the dose divider 30 and the length between the bottom surface 56 of the dose divider 30 and the proximal end of the container 11.

[0164] In Figure 10, the plunger rod 12 is in its initial starting position, and the drug 19 has not been discharged from the chamber 15 at all. Also in this initial position, the dose divider 30 is coupled to the plunger arm 12 as described above. The dose divider 30 may be in its first configuration and cannot be removed from the plunger 12 unless it is moved to its second configuration as described above, or such removal may be prevented otherwise. This can prevent the dose divider 30 from accidentally detaching from the plunger rod 12. The plunger rod 12 is translatably movable with respect to the dose divider 30 parallel to the central axis XX, thereby allowing the plunger rod 12 to slide within the channel 47 of the dose divider 30.

[0165] The user (which may be the patient if the drug is self-administered, or a healthcare worker or other user if the drug is administered to the patient by a third party) inserts the atomizer 17 (or the outlet 16 if the atomizer 17 is not present) into the patient's first nostril. The user then places their index and middle fingers on the finger grip 13 and presses the end face 20 with their thumb, moving the plunger rod 12 distally toward the distal end of the container 11 in an axial direction. This pushes the piston 18 distally within the chamber 15, forcing the drug 19 out of the outlet 16 through the drug passage of the atomizer 17, and spraying the drug so that it is inhaled by the patient.

[0166] The user continues to move the plunger rod 12 distally across this first range of motion until the plunger rod 12 can no longer be moved by the dose divider 30. That is, the user continues to move the plunger rod 12 distally across this first range of motion until the distal surface 21 of the end face 20 contacts the dose divider 30 (e.g., the upper surface 55 of the dose divider 30) and the bottom surface 56 of the dose divider 30 contacts the proximal end of the container 11, at which point the plunger rod 12 can no longer be moved distally. This first range of motion has a distance corresponding to L4.

[0167] If the dose divider 30 is initially coupled to the plunger rod 12 and the dose divider 30 is in contact with the proximal end of the container 11, the contact between the dose divider 30 and the proximal end of the container 11 causes the plunger rod 12 to translate distally within the channel 47 of the dose divider 30, and as it enters the container 11, the dose divider 30 is held in a predetermined position relative to the container 11. On the other hand, if the dose divider 30 is initially coupled closer to the proximal end of the plunger rod 12 and the dose divider 30 is not initially in contact with the proximal end of the container 11, the dose divider 30 may move together with the plunger rod 12 as the plunger rod 12 is moved distally, until the dose divider 30 eventually comes into contact with the proximal end of the container 11, and from this point onward, the dose divider 30 is fixed with respect to the container 11, and as the plunger rod 12 is moved further distally, the plunger rod 12 translates within the channel of the dose divider 30 until the distal surface 21 of the end face 20 finally comes into contact with the dose divider 30.

[0168] Figure 11 shows the syringe 10 from Figure 10 after the plunger rod 12 has moved distally through its first range of motion. At this point, the plunger rod 12 is in an intermediate position, and the first dose of the drug 19 has already been delivered to the patient. At this point, the plunger rod 12 has been moved into the container 11 by a distance equal to L4, and the distance L2 between the distal surface 21 and the proximal end of the container 11 is approximately equal to L3.

[0169] Subsequently, the user removes the syringe 10 from the first nostril and detaches the dose divider 30 from the plunger rod 12. This can be achieved by moving the dose divider 30 to its second configuration by moving the rear ends of the first arm 41 and the second arm 42 together, as described above, and by sliding the plunger rod 12 out of the channel, through the opening 58 and along axis YY opposite to the rear end of the dose divider 30. The plunger rod 12 is in an intermediate position having been moved over the first range of motion corresponding to L4, but some of the drug 19 for the subsequent dose to be delivered remains in the chamber 15.

[0170] At this point, the user inserts the atomizer 17 into the patient's other nostril. Since the dose divider 30 has been removed, the plunger rod 12 is no longer prevented from moving further distally in the axial direction by the dose divider 30. The user then pushes the end face 20 again, moving the plunger rod 12 distally in the axial direction, which pushes the piston 18 distally within the chamber 15, causing the remaining drug 19 to be discharged from the outlet 16 through the drug passage of the atomizer 17 and sprayed so that the drug is inhaled by the patient. The user continues to move the plunger rod 12 distally through this second range of motion until the distal surface 21 of the end face 20 abuts against the proximal end of the container 11 or the piston 18 abuts against the distal end of the chamber 15, preventing further distal movement. At this point, the plunger rod 12 is in the end position, and the remaining drug 19 has been discharged as the second final dose to be delivered to the patient. Figure 12 shows the syringe 10 from Figure 11 with the dose divider 30 removed and the plunger rod 12 in the end position.

[0171] Considering the above, the volumes of the first and second doses of the drug to be delivered can be controlled by controlling the first and second ranges of motion of the plunger rod 12, which can be controlled by selecting the dimensions L3 of the dose divider 30 and / or the dimensions L4 of the syringe 10 as needed. In embodiments where the first and second doses should be equal, it will be found that the dimension L3 can be selected to be equal to L4.

[0172] The aforementioned dose divider 30 provides a simple and effective method for enabling the user to reliably divide the drug delivery process into two (or more) separate doses. The dose divider 30 provides an effective method for ensuring that the drug 19 is divided as intended and that the user does not mistakenly deliver too much / all of the drug as the first dose.

[0173] The dose divider 30 may enable the administration of accurate doses without requiring the user to possess precise motor skills and / or visual acuity to confirm the dose volume.

[0174] Figure 13 is a flowchart showing a method 140 of using the dose divider 30 with the syringe 10 according to an aspect of this disclosure.

[0175] In an optional step 141, the user fills the chamber 15 of the syringe 10 with the drug 19 using any suitable technique. For example, the user may connect a needle to the syringe 10 (for example, to the outlet 16 of the syringe 10 using any suitable connector) and draw the drug 19 from the vial into the chamber 15 in the container 11 via the needle. In other examples, the syringe 10 may be pre-filled with the drug 19 before the user receives the syringe 10, for example, by a third-party manufacturer.

[0176] In an optional step 142, the user moves the dose divider 30 from its first configuration to its second configuration, as described above.

[0177] In an optional step 143, the user connects the dose divider 30 to the plunger rod 12 of the syringe 10 in the manner described above.

[0178] In some cases, the dose divider 30 may already be attached to the syringe 10 before the user receives the syringe 10, for example, by a third-party manufacturer, in which case steps 142 and 143 do not need to be performed.

[0179] In step 144, the user discharges the first dose of medication by moving the plunger rod 12 within the first range of motion in the manner described above.

[0180] If the needle is attached to the syringe 10 and used to draw the drug 19 from the vial, the user will remove the needle from the syringe 10 after drawing the drug 19, but before dispensing the first dose.

[0181] When dispensing a dose using the atomizer 17, the user attaches the atomizer 17 to the outlet 16 of the syringe 10 if it has not been attached beforehand. This is done before dispensing the first dose of the drug 19, and after removing the needle from the syringe 10 if the needle was used to draw out the drug 19 as described above.

[0182] In step 145, the user removes the dose divider 30 from the plunger rod 12 of the syringe 10 in the manner described above.

[0183] In step 146, the user discharges the second dose of medication by moving the plunger rod 12 through a second range of motion in the manner described above.

[0184] While a specific example is described in which the dose divider 30 can be slid along the plunger rod 12 when coupled to it, it should be understood that in other examples, the dose divider 30 may be configured not to slide along the plunger rod 12 when coupled to it, or such movement may be substantially prevented. In such a situation, the user will couple the dose divider 30 to its initial position along the plunger rod 12 so that the dose divider 30 does not initially contact the proximal end of the container 11 (i.e., there is separation between the bottom surface 56 of the dose divider 30 and the proximal end of the container 11). Thus, the user can move the plunger rod 12 distally over a first range of motion corresponding to a distance that can be set to correspond to a first dose between the dose divider 30 and the proximal end of the container 11. Subsequently, the user may remove the dose divider 30 and move the plunger rod 12 distally over a second range of motion equal to the dimension L3 of the removed dose divider 30 (if the dose divider 30 is not initially connected to the plunger rod and the upper surface 55 of the dose divider 30 is in contact with the distal surface 21 of the end face 20, this is the sum of the distance between the upper surface 55 of the dose divider 30 and the distal surface 21 of the end face 20).

[0185] It should be understood that aspects of this disclosure may be used to deliver three or more precise doses of drug 19 from a syringe 10. For example, two or more dose dividers 30 may be coupled to a plunger rod 12, with each dose divider 30 coupled to the plunger rod 12 in the same manner as described with respect to Figures 7-9, but with each dose divider 30 spaced apart along the axial length of the plunger rod 12 (along axis XX). The dimensions L2 of each dose divider 30 may be selected to correspond to the amount of drug 19 discharged when the dose divider 30 is detached from the plunger rod 12 and the plunger rod 12 is moved distally over a distance L2.

[0186] If each of the multiple dose dividers 40 can slide freely axially along the plunger rod 12, the dose dividers 40 can be removed in any order chosen by the user to dispense the dose of medication corresponding to the dimension L2 of the dose divider being removed. This provides flexibility in the order in which doses are delivered. On the other hand, if the dose dividers 40 are configured not to slide axially along the plunger rod 12 (or such sliding is prevented), this may require the user to remove the multiple dose dividers 40 in a specific order to ensure that all doses are dispensed correctly. More specifically, the dose dividers 40 should be removed starting with the dose divider 30 closest to the proximal end of the container 11, then the next closest dose divider 30, and so on, until the dose divider 30 furthest from the container 11 is removed, with medication 19 being dispensed each time a dose divider 40 is removed. This situation ensures that specific doses are administered in a specific order, which may improve safety and / or compliance.

[0187] The dose divider 30 can be used with conventional syringes, without necessarily having to adapt these syringes to the dose divider 30. Alternatively, the dose divider 30 may be designed to be adapted for use with a specific syringe 10 and / or drug 19 by adjusting one or more dimensions of the dose divider, such as dimensions L3, W1, W2, or W3.

[0188] The dose divider 30 described herein may be easy for the user to use and control, for example, when attaching the dose divider 30 to and / or reattaching it to the plunger rod 12. For example, by providing a first arm 41 including a front portion 44a and a rear portion 45a, a second arm 42 including a front portion 44b and a rear portion 45b, and an elastic hinge 49 connecting the first arm 41 and the second arm 42, a dose divider 30 that can be attached to and detached from the plunger rod 12 can be obtained simply by compressing the rear portions 45a and 45b together and separating the front portions 44a and 44b together. Thus, the dose divider 30 may be easy to operate. By providing the front sections 44a, 44b and rear sections 45a, 45b that extend over a substantial distance from the elastic hinge 49, the lever effect provided by the first and second arms 41, 42 and the elastic hinge 49 allows the front sections 44a, 44b to be separated from each other by applying only a relatively small compressive force to the rear sections 45a, 45b. The dose divider 30 may be easier to use and / or control for users with impaired manual dexterity.

[0189] The dose divider 30 described herein may be easier to reuse. For example, by providing a first arm 41 including a front portion 44a and a rear portion 45a, a second arm 42 including a front portion 44b and a rear portion 45b, and an elastic hinge 49 connecting the first arm 41 and the second arm 42, the dose divider 30 may be repeatedly attached to and detached from the plunger rod 12 of the syringe 10. Thus, the dose divider 30 may be reusable rather than single-use. The arrangement of the elastic hinge 49 described herein allows the first arm 41 and the second arm 42 to pivot repeatedly reciprocating relative to each other, so that the elastic hinge 49 does not deteriorate as much, thereby extending the life of the dose divider 30.

[0190] The dose divider 30 described herein can be used flexibly. For example, it can be mounted along the plunger rod 12 at many different positions, such as the proximal end of the plunger rod 12, the distal end of the plunger rod 12, or an intermediate point between the proximal and distal ends of the plunger rod 12. Furthermore, the dose divider 30 may be easier to reposition on the plunger rod 12 after it has been mounted. For example, it may be easier to move the dose divider 30 from a position closer to the proximal end of the plunger rod 12 to a position closer to the distal end of the plunger rod 12, for example, by squeezing the rear portions 45a and 45b together to slide the dose divider 30 along the plunger rod 12, and then releasing the rear portions 45a and 45b. Such flexibility can be achieved by providing a first arm 41 including a front portion 44a and a rear portion 45a, a second arm 42 including a front portion 44b and a rear portion 45b, and an elastic hinge 49 connecting the first arm 41 and the second arm 42.

[0191] The dose divider 30 described herein can be coupled to multiple types of plunger rods 12, for example, plunger rods 12 each having a different cross-section in terms of size and / or shape. Depending on the configuration of the dose divider 30, such as the arrangement of the elastic hinge 49, the dose divider 30 may be adaptable to a particular plunger rod 12 to which it is attached, so that the opening 58 and channel 47 can expand or contract as needed to insert the plunger rod 12 into the channel 47 and then hold it securely. The cross-sectional profile of the channel 47 may be customized to match the cross-sectional profile of a particular plunger rod 12 and / or multiple plunger rods 12. The dose divider 30 described herein may be adaptable to plunger rods 12 of different shapes.

[0192] Aspects of the present disclosure may be used for nasal drug administration. For example, the drug 19 contained in the syringe 10 may contain a respiratory syncytial virus (RSV) vaccine in which the required vaccine dose is 0.1 mL per nostril. In this example, the user may fill the container 11 of the syringe 10 with 0.2 mL of the vaccine drug 19 before attaching the dose divider 30 to the plunger rod 12 of the syringe 10, as described above. In this example, the dose divider 30 should have a dimension L2 corresponding to the length of the plunger rod 12, which allows for the delivery of 0.1 mL of vaccine (i.e., one dose per nostril). For example, the dose divider may have a dimension L2 of 16 mm to 19 mm, for example, a dimension L2 of 17 mm to 18 mm, or more specifically, a dimension L2 equal to 17.5 mm. The user administers a 0.1 mL dose of vaccine into the patient's first nostril in the manner described above, then removes the dose divider 30 and administers the remaining 0.1 mL of the second dose of vaccine into the patient's second nostril. In some cases, the required vaccine dose may be other than 0.1 mL per nostril, and in some cases, the drug 19 may be a type of vaccine other than the RSV vaccine, or a non-vaccine drug 19. In some cases, embodiments of the present disclosure may be used for forms of drug delivery other than intranasal administration, such as subcutaneous injection or intramuscular injection, but are not limited to these.

[0193] In some examples, it is stated that the user attaches the dose divider 30 to the plunger rod 12 of the syringe 10 before administering the drug. However, in some examples, it should be understood that the dose divider 30 is already attached to the plunger rod 12 before the user receives the syringe 10, for example, by a third-party manufacturer.

[0194] In some cases, the user administering the drug may fill the syringe container 11 with the drug 19 before, for example, connecting the dose divider 30 to the plunger rod 12. However, in other cases, the syringe container 11 may be pre-filled with the drug 19 before the user receives the syringe 10, for example, by a third-party manufacturer.

[0195] This specification describes systems, apparatus, components, and methods that may be related to the delivery of respiratory syncytial virus (RSV) vaccines using nasal spray administration devices.

[0196] As used herein, “RSVΔNS2 / Δ1313 / I1314L” refers to RSVΔNS2 / Δ1313 / I1314L(NIH) or RSVΔNS2 / Δ1313 / I1314L(Sanofi). Each of ΔNS2 / Δ1313 / I1314L(NIH) and RSVΔNS2 / Δ1313 / I1314L(Sanofi) contains attenuated live RSV resulting from (i) a 523-nucleotide (nt) deletion in the NS2 gene (ΔNS2), (ii) an amino acid deletion in the L protein, and (iii) a genetically stabilizing mutation in the L gene. The attenuated live RSV of RSVΔNS2 / Δ1313 / I1314L(Sanofi) also contains a nucleotide modification at position 14456, representing a change from thymine (T) to adenine (A) in the non-coding region.

[0197] As used herein, “RSVΔNS2 / Δ1313 / I1314L vaccine” refers to “RSVΔNS2 / Δ1313 / I1314L(NIH) vaccine” or “RSVΔNS2 / Δ1313 / I1314L(Sanofi) vaccine.” RSVΔNS2 / Δ1313 / I1314L(NIH) vaccine contains an effective dose of RSVΔNS2 / Δ1313 / I1314L(NIH). RSVΔNS2 / Δ1313 / I1314L(Sanofi) vaccine contains an effective dose of RSVΔNS2 / Δ1313 / I1314L(Sanofi).

[0198] Exemplary Method and Use In some embodiments, a method is provided for delivering a dose of RSV vaccine using a nasal spray administration device.

[0199] In some embodiments, a nasal spray administration device is used in a method for administering a dose of an RSV vaccine containing attenuated live RSV. In some embodiments, a method is provided for administering a dose of an RSV vaccine using a nasal spray administration device, wherein the RSV vaccine comprises an effective amount of attenuated live RSV (RSVΔNS2 / Δ1313 / I1314L(NIH) vaccine) having (i) a 523 nucleotide (nt) deletion in the NS2 gene (ΔNS2), (ii) an amino acid deletion in the L protein, and (iii) a genetically stabilizing mutation in the L gene, or an RSVΔNS2 / Δ1313 / I1314L(Sanofi) vaccine further comprising nucleotide modifications in the non-coding region representing a change from thymine (T) to adenine (A). In some embodiments, the codon encoding serine at position 1313 of the L protein is deleted, resulting in a deletion of an amino acid in the L protein (Δ1313). In some embodiments, a genetically stabilizing mutation in the L gene (I1314L) results from a leucine amino acid residue substitution for isoleucine at position 1314.

[0200] In some embodiments, a method is provided for administering a dose of RSV vaccine using a nasal spray administration device. In some embodiments, the pediatric patient may be between 6 and 18 months of age.

[0201] In some embodiments, the RSV vaccine is administered intranasally using a nasal spray dispenser, with approximately half a dose delivered to each nostril. In some embodiments, the RSV vaccine is administered intranasally so that the entire dose is delivered to one nostril. In some embodiments, the RSV vaccine is administered intranasally with half a dose delivered to one nostril, and the remaining half dose delivered to the same nostril after the first half dose has been absorbed. In some embodiments, the RSV vaccine is administered intranasally using a nasal spray dispenser, with different doses delivered to one or both nostrils.

[0202] In some embodiments, the RSV vaccine is administered intranasally in a liquid formulation using a nasal spray dispenser. In some embodiments, the RSV vaccine dose is administered intranasally at approximately 0.2 mL using a nasal spray dispenser. In some embodiments, a 0.2 mL dose is administered intranasally, with approximately 0.1 mL delivered to each nostril. In some embodiments, the RSV vaccine dose is administered intranasally at approximately 0.01 mL, 0.02 mL, 0.05 mL, 0.1 mL, 0.2 mL, 0.3 mL, 0.4 mL, 0.5 mL, 0.6 mL, 0.7 mL, 0.8 mL, 0.9 mL, 1.0 mL, 1.1 mL, 1.2 mL, 1.3 mL, 1.4 mL, or 1.5 mL using a nasal spray dispenser. As described above, the dose may be divided equally between two nostrils, unevenly between two nostrils, or the entire amount may be delivered to one nostril in one or more deliveries.

[0203] In some embodiments, a method is provided in which a first dose of the RSV vaccine is administered using a nasal spray administration device, and a second dose of the RSV vaccine is administered using a nasal spray administration device.

[0204] In some embodiments, a method is provided for administering a first dose of RSV vaccine using a nasal spray dosing device, which includes a spray nozzle that sprays the RSV vaccine and directs the spray chamber from the top of the nasal passage toward the nasal cavity. In some embodiments, a method is provided for administering a dose of RSV vaccine using a nasal spray dosing device, which includes a spray nozzle that sprays the RSV vaccine and directs the spray chamber from the top of the nasal passage toward the nasal cavity. In some embodiments, a nasal spray dosing device includes a barrel operationally connected to the spray nozzle and a plunger that is movable within the barrel and advances the RSV vaccine through the spray nozzle. In some embodiments, a nasal spray dosing device further includes a dose divider for dividing the dose of RSV vaccine into two or more deliveries. In some embodiments, a dose divider can divide the dose of RSV vaccine into about half the volume to be delivered to the subject. In some embodiments, a dose divider is used to deliver half doses to each nostril of the subject.

[0205] In some embodiments, the nasal spray delivery device delivers an average droplet size D of 10 to 120 μm V50 In some embodiments, the nasal spray delivery device delivers an average droplet size D of 10 to 120 μm, about 30 to 110 μm, about 50 to 110 μm, about 70 to 110 μm, or about 80 to 110 μm V50 In some embodiments, the nasal spray delivery device delivers an average shot weight of about 95 mg to about 135 mg, about 100 mg to about 130 mg, or about 100 mg to about 130 mg, or about 100 mg to about 130 mg, or about 105 mg to about 130 mg. In some embodiments, the nasal spray delivery device delivers an average shot volume of about 85 μL to about 120 μL, about 90 μL to about 115 μL, or about 95 μL to about 115 μL

[0206] In some embodiments, provided is the use of the nasal spray delivery device described herein for administering a dose of an RSV vaccine to a subject, the RSV vaccine comprising an effective amount of live attenuated RSV. In some embodiments, the use is of a live attenuated RSV (RSVΔNS2 / Δ1313 / I1314L (NIH) vaccine) that has a 523 nucleotide (nt) deletion in the NS2 gene (ΔNS2), an amino acid deletion in the L protein, and a genetic stabilizing mutation in the L gene, or an RSVΔNS2 / Δ1313 / I1314L (Sanofi) vaccine that further comprises a nucleotide modification in a non-coding region that represents a change from thymine (T) to adenine (A)

[0207] Immunogenicity In both the low-dose and high-dose groups, approximately 70 percent (70%) of vaccinated individuals achieved a quadruple increase in neutralizing antibody titer after a second dose, in contrast to 61% and 47% after a single dose in the low-dose and high-dose RSV-naive groups. This increase in the proportion of participants achieving a quadruple increase after a second dose supports the appropriateness of using a second dose in this population. The 70% who achieved this doubling after a second dose are consistent with the expected clinical efficacy target of 70% for this candidate. A quadruple increase in serum neutralizing antibody titer was achieved in 75% after one or two doses of vaccination. The proportion of RSV-experienced participants (36% and 22% in the low-dose and high-dose groups, respectively) also achieved a quadruple increase in neutralizing antibody titer after vaccination, suggesting potential benefits for this subgroup as well. It should be noted that this is derived from a moderate sample of participants at this point in the interim analysis (20 out of 97 vaccinated individuals).

[0208] In summary, these data strongly support the use of the RSVΔNS2 / Δ1313 / I1314L(Sanofi) vaccine in duration-of-effect studies of candidates, including administration at 5.6 and 6.2 log PFU / dose.

[0209] Vaccine virus shedding and infectivity After each vaccine administration, viral infectivity was assessed by examining vaccine virus shedding in addition to neutralizing antibody titers or doubling of serum IgG levels. High levels of vaccine infectivity (over 80% and over 70% in the RSV-naive groups after the first and second doses, respectively) support the vaccine candidate as a promising candidate associated with good immunity acquisition. When infectivity was examined after either vaccine administration, over 90% of participants had evidence of infection. Relatively high infectivity was observed in a small cohort of participants who had experienced RSV (80% and 33.3% in low-dose and high-dose recipients after the first dose, and 60% and 50% after the second dose), suggesting the potential of this group. In addition, the rate of vaccine virus shedding in RSV-naive participants after the second dose (approximately 20%) was significantly lower compared to after the first dose (over 70%), as previously reported in the literature for other effective attenuated live mucosal virus vaccines, and subsequent "challenges" in the form of second vaccination are characterized by a significant decrease in vaccine virus shedding. It should be noted that the shedding data available for this cohort was from a single time point after each vaccination (7 days post-vaccination). While this coincides with the peak time of viral shedding reported in the literature for other RSV live attenuated vaccine (LAV) trials, some shedding may have been missed. Given this limitation of available shedding data, the results obtained are particularly encouraging.

[0210] Overall conclusion The interim analysis results showed promising safety, immunogenicity, and infectivity profiles for the RSVΔNS2 / Δ1313 / I1314L(Sanofi) candidate.

[0211] No safety concerns were identified after administration of one or two dose levels of the clinical trial RSVΔNS2 / Δ1313 / I1314L(Sanofi) vaccine, or based on baseline serological status.

[0212] Conclusions regarding immunogenicity based on vaccine virus shedding and baseline IgA serostatism indicate that significant immunity acquisition was demonstrated at both dose levels, with 70% of RSV-naive vaccine recipients achieving a 4-fold response in serum neutralizing antibody response after a second dose at both dose levels compared to RSV-naive participants. [Explanation of Symbols]

[0213] 10 syringes 11. Medication container 12 Plunger Rods 13 Finger Grips 14. Outer side wall of the container 15. Drug Chamber 16 Exit 17 Atomizer 18 pistons 19. Medications 20 End face 21 Distal surface 30 Dose Divider 41 First Arm 42 Second Arm 44a Front of the first arm 44b Front of the second arm 45a Rear of the first arm 45b Rear of the second arm 46a Front inner surface of the first arm 46b Front inner surface of the second arm 47 channels 48a Rear inner surface of the first arm 48b Rear inner surface of the second arm 49 Elastic hinge 50a First straight section 50b Second straight section 51 Curved section 52a, 52b Grip configuration 53a Rear outer surface of the first arm 53b Rear outer surface of the second arm 54a~f, 54a'~f' Ridge 55 Top 56 Bottom 57a, 57b Lip 58 Opening 60 First guide surface 61 Second guide surface 62 Block Features 63 First block protrusion 64 Second block projection 66 Stop Configuration 67 First projection 68 Second projection 69 Groove 70 Drug delivery devices

Claims

1. A method for using a dose divider (30), wherein the dose divider is A first arm (41) and a second arm (42) facing the first arm, each including its respective front portion (44a, 44b), the front portion (44a) of the first arm and the front portion (44b) of the second arm forming a channel (47) between them for receiving the plunger rod (12) of the syringe (10), the first arm (41) and the second arm (42), To enable the dose divider to move reversibly between the first configuration and the second configuration, an elastic hinge (49) is provided to pivotally connect the first arm and the second arm. Includes, When the dose divider is in the second configuration, the dose divider is configured to receive the plunger rod in the channel through an opening formed between the front portion of the first arm and the front portion of the second arm, and the channel has a shape configured to receive a specific outer shape of the plunger rod. The front portion of the first arm and the front portion of the second arm are closer together when the dose divider is in the first configuration than when the dose divider is in the second configuration, and the method is Moving the dose divider from the first configuration to the second configuration by applying force to the first arm (41) and the second arm (42) such that the first arm pivots in a first direction relative to the second arm using the elastic hinge (49). Methods that include...

2. The method according to claim 1, wherein the first arm (41) and the second arm (42) of the dose divider each include their respective rear portions (45a, 45b), and applying the force to the first arm (41) and the second arm (42) includes applying the force to the rear portion (45a) of the first arm and the rear portion (45b) of the second arm such that the rear portion (45a) of the first arm and the rear portion (45b) of the second arm pivot toward each other, and the front portion (44a) of the first arm and the front portion (44b) of the second arm pivot toward each other in opposite directions.

3. The rear portion of the first arm includes a first projection (67), and the rear portion of the second arm includes a second projection (68). The aforementioned method, Move the rear portion of the first arm toward the rear portion of the second arm so that the first projection and the second projection come into contact with each other, thereby restricting further movement of the rear portion of the first arm toward the rear portion of the second arm. It further includes, Optionally, the first projection includes a groove (69) configured to receive at least a portion of the second projection when the first projection and the second projection are in contact with each other. The method according to claim 2.

4. The method according to claim 2 or 3, wherein the outer surface of the rear of the first arm and the outer surface of the rear of the second arm each include a grip configuration (52a, 52b), and optionally each grip configuration includes a plurality of ridges (54a-f, 54a'-f').

5. The dose divider includes a stop configuration (66) located at least one of the rear of the first arm or the rear of the second arm, The method according to any one of claims 2 to 4, wherein the stop configuration is positioned between the first arm and the second arm to restrict the rear portion of the first arm from moving toward the rear portion of the second arm.

6. After moving the dose divider from the first configuration to the second configuration, the force applied to the first arm (41) and the second arm (42) is released so that the first arm pivots in a second direction opposite to the first direction relative to the second arm using the elastic hinge (49), thereby moving the dose divider from the second configuration to the first configuration. The method according to any one of claims 1 to 5, further comprising:

7. While the dose divider is in the second configuration, the dose divider is coupled to the plunger rod (12) of the syringe (10), or the dose divider is detached from the plunger rod (12) of the syringe (10). The method according to any one of claims 1 to 6, further comprising:

8. While the dose divider is connected to the plunger rod (12) of the syringe (10), the plunger rod is moved within a first range of motion relative to the syringe container (11) in order to dispense a dose of the drug contained in the syringe. The method according to any one of claims 1 to 7, including

9. The method according to any one of claims 1 to 8, wherein the elastic hinge is configured to bias the dose divider toward the first configuration.

10. The method according to any one of claims 1 to 9, wherein the front portion of the first arm and the front portion of the second arm each include a guide surface (60, 61) for guiding the plunger rod through the opening toward the channel.

11. The method according to any one of claims 1 to 10, wherein the dose divider includes at least one of a first block projection (63) and a second block projection (64) positioned between the channel and the elastic hinge to prevent the plunger rod from exiting the channel.

12. The method according to any one of claims 1 to 11, wherein the elastic hinge includes a curved portion (52) connected to each of the straight portions (50a, 50b) at each end.

13. The method according to claim 12, wherein the curved portion is curved toward the opposite side from the front end of the dose divider such that the apex of the curved portion is at the rear of the elastic hinge.

14. The method according to any one of claims 1 to 11, wherein the elastic hinge is arch-shaped.

15. A method for using the system, wherein the system is The vial containing the drug, A syringe (10) including a container (11) and a plunger rod (12), A needle, configured to be attached to the syringe so that the drug can be drawn from the vial into the container (11) via the needle, An atomizer (17) configured to be coupled to the syringe, A dose divider (30) configured to move reversibly from a first configuration to a second configuration, wherein when the dose divider is in the second configuration, the dose divider is configured to receive the plunger rod, and when the dose divider is in the first configuration, the dose divider is configured to be coupled to the plunger rod, and Includes, The aforementioned method, While the needle is connected to the syringe, the drug is drawn from the vial into the container of the syringe via the needle, The dose divider is connected to the plunger rod, Removing the needle from the syringe, The atomizer (17) is attached to the syringe, While the dose divider is coupled to the plunger rod and the atomizer is coupled to the syringe, the plunger rod is moved within a first range of motion relative to the container of the syringe in order to discharge a first dose of the drug (19) from the container to the atomizer. After discharging the first dose of the drug, the dose divider is removed from the plunger rod. While the dose divider is detached from the plunger rod and the atomizer is coupled to the syringe, the plunger rod is moved within a second range of motion relative to the container in order to discharge a second dose of the drug from the container out of the atomizer. Methods that include...

16. The method according to claim 15, wherein at least a portion of the atomizer is inserted into the patient's first nostril while the first dose of the drug is being dispensed, and at least a portion of the atomizer is inserted into the patient's second nostril while the second dose of the drug is being dispensed.

17. The method according to claim 15 or 16, comprising attaching the needle to the syringe before drawing the drug from the vial into the syringe.

18. The method according to any one of claims 15 to 17, wherein the drug comprises a vaccine, and optionally the vaccine is an RSV vaccine.

19. The dose divider includes a first arm (41) and a second arm (42), each including a front section (44a, 44b) and a rear section (45a, 45b), The dose divider is configured such that the user can move from the first configuration to the second configuration by moving the rear portion (45a) of the first arm toward the rear portion (45b) of the second arm. The method according to any one of claims 15 to 18.

20. The dose divider includes a stop configuration (66) located at least one of the rear of the first arm or the rear of the second arm, The stop configuration (66) is positioned between the first arm and the second arm to restrict the rear portion of the first arm from moving toward the rear portion of the second arm. The method according to claim 19.

21. The stop configuration includes a first projection (67) located on the rear of the first arm and a second projection (68) located on the rear of the second arm. The first projection and the second projection are configured to contact each other when the rear portion of the first arm is moved toward the rear portion of the second arm, in order to restrict the rear portion of the first arm from moving further toward the rear portion of the second arm. Optionally, the first projection includes a groove (69) configured to receive at least a portion of the second projection when the first projection and the second projection are in contact with each other. The method according to claim 20.

22. A method for using a dose divider (30), wherein the dose divider is A first arm (41) and a second arm (42) facing the first arm, each including its respective front portion (44a, 44b), wherein the front portion (44a) of the first arm and the front portion (44b) of the second arm form a channel (47) between them for receiving the plunger rod (12) of the syringe (10), the first arm and the second arm, To enable the dose divider to move reversibly between the first configuration and the second configuration, an elastic hinge (49) is provided to pivotally connect the first arm and the second arm. Includes, When the dose divider is in the second configuration, the dose divider is configured to receive the plunger rod in the channel through an opening formed between the front portion of the first arm and the front portion of the second arm, and the channel has a shape configured to receive a specific outer shape of the plunger rod. The front portion of the first arm and the front portion of the second arm are closer together when the dose divider is in the first configuration than when the dose divider is in the second configuration, and the method is While the dose divider is coupled to the plunger rod of the syringe, the plunger rod is moved within a first range of motion relative to the syringe container to discharge a first dose of the drug (19) contained in the syringe, Removing the dose divider from the plunger rod, While the dose divider is detached from the plunger rod, the plunger rod is moved within a second range of motion relative to the container to discharge a second dose of the drug contained in the syringe. Methods that include...

23. A method for using a dose divider (30), To move the dose divider from the first configuration to the second configuration, force is applied to the first arm (41) and the second arm (42) of the dose divider, and the first arm is pivoted in the first direction relative to the second arm using the elastic hinge (49) connecting the first arm and the second arm. Includes, A method wherein, when the dose divider is in a second configuration, the dose divider is configured to receive the plunger rod of a syringe (10) in a channel formed between the front of the first arm and the front of the second arm.

24. The method according to claim 23, wherein the first arm (41) and the second arm (42) of the dose divider each include their respective rear portions (45a, 45b), and applying the force to the first arm (41) and the second arm (42) includes applying the force to the rear portion (45a) of the first arm and the rear portion (45b) of the second arm such that the rear portion (45a) of the first arm and the rear portion (45b) of the second arm pivot toward each other and the front portion (44a) of the first arm and the front portion (44b) of the second arm pivot toward each other in opposite directions.

25. The method according to claim 24, comprising moving the rear portion of the first arm toward the rear portion of the second arm such that the first projection on the rear portion of the first arm and the second projection on the rear portion of the second arm come into contact with each other, thereby restricting further movement of the rear portion of the first arm toward the rear portion of the second arm.

26. The method according to claim 25, wherein the first projection includes a groove (69) configured to receive at least a portion of the second projection when the first projection and the second projection are in contact with each other.

27. The method according to any one of claims 24 to 26, wherein the outer surface of the rear of the first arm and the outer surface of the rear of the second arm include their respective grip configurations (52a, 52b).

28. The method according to claim 27, wherein each grip configuration includes a plurality of ridges (54a-f, 54a'-f').

29. The dose divider includes a stop configuration (66) located at least one of the rear of the first arm or the rear of the second arm, The method according to any one of claims 24 to 28, wherein the stop configuration is positioned between the first arm and the second arm to restrict the rear portion of the first arm from moving toward the rear portion of the second arm.

30. The method according to any one of claims 23 to 29, further comprising moving the dose divider from the first configuration to the second configuration, and then moving the dose divider from the second configuration to the first configuration by releasing the force applied to the first arm (41) and the second arm (42) such that the first arm pivots in a second direction opposite to the first direction with respect to the second arm using the elastic hinge (49).

31. The method according to any one of claims 23 to 30, comprising coupling the dose divider to the plunger rod (12) of the syringe (10) or detaching the dose divider from the plunger rod (12) of the syringe (10) while the dose divider is in the second configuration.

32. The method according to any one of claims 23 to 31, comprising moving the plunger rod (12) of the syringe (10) within a first range of motion with respect to the container (11) of the syringe in order to discharge a dose of the drug contained in the syringe.

33. The method according to any one of claims 23 to 32, wherein the elastic hinge is configured to bias the dose divider toward the first configuration.

34. The method according to any one of claims 23 to 33, wherein the front portion of the first arm and the front portion of the second arm each include a guide surface (60, 61) for guiding the plunger rod toward the channel through an opening formed between the front portion of the first arm and the front portion of the second arm.

35. The method according to any one of claims 23 to 34, wherein the dose divider includes at least one of a first block projection (63) and a second block projection (64) positioned between the channel and the elastic hinge to prevent the plunger rod from exiting the channel.

36. The method according to any one of claims 23 to 35, wherein the elastic hinge includes a curved portion (52) connected to each of the straight portions (50a, 50b) at each end.

37. The method according to claim 36, wherein the curved portion is curved toward the opposite side from the front end of the dose divider such that the apex of the curved portion is at the rear of the elastic hinge.

38. The method according to any one of claims 23 to 37, wherein the elastic hinge is arch-shaped.

39. A method of using the system, While the needle is connected to the syringe of the system, the drug is drawn from the vial of the system into the container of the syringe via the needle. The dose divider is connected to the plunger rod of the syringe, Removing the needle from the syringe, The atomizer (17) is attached to the syringe, While the dose divider is coupled to the plunger rod and the atomizer is coupled to the syringe, the plunger rod is moved within a first range of motion relative to the container of the syringe in order to discharge a first dose of the drug (19) from the container to the atomizer. After discharging the first dose of the drug, the dose divider is removed from the plunger rod. While the dose divider is detached from the plunger rod and the atomizer is coupled to the syringe, the plunger rod is moved within a second range of motion relative to the container in order to discharge a second dose of the drug from the container out of the atomizer. Methods that include...

40. The method according to claim 39, wherein at least a portion of the atomizer is inserted into the patient's first nostril while the first dose of the drug is being dispensed, and at least a portion of the atomizer is inserted into the patient's second nostril while the second dose of the drug is being dispensed.

41. The method according to claim 39 or 40, comprising attaching the needle to the syringe before drawing the drug from the vial into the syringe.

42. The method according to any one of claims 39 to 41, wherein the drug comprises a vaccine, and optionally the vaccine is an RSV vaccine.

43. The dose divider includes a first arm (41) and a second arm (42), each including a front section (44a, 44b) and a rear section (45a, 45b), The dose divider is configured to move from the first configuration to the second configuration by the user moving the rear portion (45a) of the first arm toward the rear portion (45b) of the second arm, and when the dose divider is in the second configuration, it is configured to receive the plunger rod, and when the dose divider is in the first configuration, it is configured to be coupled to the plunger rod. The method according to any one of claims 39 to 42.

44. The dose divider includes a stop configuration (66) located at least one of the rear of the first arm or the rear of the second arm, The stop configuration (66) is positioned between the first arm and the second arm to restrict the rear portion of the first arm from moving toward the rear portion of the second arm. The method according to claim 43.

45. The stop configuration includes a first projection (67) located on the rear of the first arm and a second projection (68) located on the rear of the second arm. The first projection and the second projection are configured to contact each other when the rear portion of the first arm is moved toward the rear portion of the second arm, in order to restrict the rear portion of the first arm from moving further toward the rear portion of the second arm. The method according to claim 44.

46. The method according to claim 44 or 45, wherein the first projection includes a groove (69) configured to receive at least a portion of the second projection when the first projection and the second projection are in contact with each other.

47. While the dose divider is coupled to the plunger rod of the syringe, the plunger rod is moved within a first range of motion relative to the syringe container in order to discharge a first dose of the drug (19) contained in the syringe, The dose divider is removed from the plunger rod, While the dose divider is detached from the plunger rod, the plunger rod is moved within a second range of motion relative to the container in order to discharge a second dose of the drug contained in the syringe. A method for using a dose divider (30), including the method described above.

48. The aforementioned dose divider is A first arm (41) and a second arm (42) facing the first arm, each including its respective front portion (44a, 44b), the front portion (44a) of the first arm and the front portion (44b) of the second arm forming a channel (47) between them for receiving the plunger rod (12) of the syringe (10), the first arm (41) and the second arm (42), To enable the dose divider to move reversibly between the first configuration and the second configuration, an elastic hinge (49) is provided to pivotally connect the first arm and the second arm. Includes, When the dose divider is in the second configuration, the dose divider is configured to receive the plunger rod in the channel through an opening formed between the front portion of the first arm and the front portion of the second arm, and the channel has a shape configured to receive a specific outer shape of the plunger rod. The front portion of the first arm and the front portion of the second arm are closer when the dose divider is in the first configuration than when the dose divider is in the second configuration. A method of using the dosage divider (30) according to claim 47.

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