Drug delivery device and precise delivery method for injectable drugs

Abstract

A method and system for operating a syringe-based drug delivery device to expel a dose of fluid from a delivery catheter, such as a needle, is described herein. The method involves advancing a plunger rod of a syringe-based drug delivery device from a dose start position to a dose end position in an axial direction of the plunger rod. This in turn advances a plunger plug in the barrel of the syringe-based drug delivery device. The plunger tip is compressed when the plunger rod reaches the dose end position for the first time. The difference between the dose start position and the dose end position takes into account compression of the plunger plug due to resistance of the fluid when expelled through the delivery conduit.

Description

Cross - Reference to Related Applications

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 416,825, filed on October 17, 2022, entitled "Novel Drug Delivery Device for Precision Delivery of Injectable Drugs", the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0002] This application relates generally to injectable drug delivery devices, and more particularly, to devices for injecting sub-milliliter volumes of viscous injectable formulations. Background Art

[0003] Syringes are commonly used to administer injectable therapeutic agents or fluids. As Figure 1 shown, a syringe typically consists of a cylindrical syringe barrel, an elastic plunger head (which slides along the axis of the syringe barrel when the user manipulates the plunger rod), and a needle. The plunger head, syringe barrel, and needle enclose a drug fluid chamber, and the needle tip provides the only outlet for the drug fluid.

[0004] Due to the emergence of high-intensity biopharmaceuticals, bispecific antibody therapies, and long-acting formulations, the viscosity of drug formulations has been increasing. The Hagen-Poiseuille equation (shown below) can be used to demonstrate the relationship between the injection force (F) required during drug delivery and the viscosity (μ) of the formulation. Q – volumetric flow rate, μ – dynamic viscosity, L – needle length, D – inner diameter of the needle, A – inner cross-sectional area of the syringe

[0005] The Hagen-Poiseuille equation shows that an increase in viscosity results in an increase in the required injection force, and how other parameters (such as the inner diameter of the needle and the diameter of the syringe) affect the injection force. The Hagen-Poiseuille equation also shows that even for drug formulations with low viscosities, very thin needles (such as those used in subretinal injections) can result in high injection forces.

[0006] In a traditional syringe, the resilient plunger head is compressible. When a user advances the plunger rod to administer the drug contained in the syringe, the drug solution is pressurized, thereby forcing the fluid through the needle. For high-viscosity formulations and / or when injecting formulations through a fine needle, the pressure within the fluid chamber may increase to an extent that causes compression of the plunger head, even as the drug is being dispensed through the needle. Thus, some portion of the user input for injecting the drug fluid may result in axial compression (and radial displacement) of the plunger head rather than injection of the drug fluid. In such cases, even though the user's tactile feedback may indicate that injection is occurring, in reality the user may simply be compressing the plunger. In the case of larger volumes (in milliliters), this effect (axial compression of the plunger head) is a small fraction of the axial travel distance of the plunger head advanced to administer the entire dose. However, for sub-milliliter volumes, the degree of axial compression of the plunger head, for high-viscosity formulations and / or when injecting formulations through a fine needle, may have a significant impact on delivering the expected dose volume relative to the axial travel distance of the plunger head. Thus, if the amount of axial user input does not account for axial compression, the plunger head may not achieve the axial travel distance required to administer the entire dose and may result in under-dosing.

[0007] In applications where the user (e.g., a clinician) cannot visually inspect the plunger head during injection, such as in intraocular injections, the user may rely solely on touch, which can be misleading in the case of sub-milliliter doses described above. Additionally, injection devices incorporating traditional syringes are designed to axially advance the plunger head a certain distance without considering plunger head compression, which can result in significant under-dosing when administering sub-milliliter volumes of drug. Thus, viscous formulations, sub-milliliter dose volumes, and / or injecting sub-milliliter volumes through very fine injection needles may exacerbate the drug delivery challenges of using syringes or syringe-based systems. SUMMARY OF THE INVENTION

[0008] Embodiments of the present disclosure are directed to providing methods and syringe-based drug delivery device designs to address the challenges in applications involving high injection forces to inject sub-milliliter volumes. In certain embodiments, an exemplary injection device can ensure accurate and precise injection of sub-milliliter doses when plunger head compression occurs. To account for plunger head compression, the injection stroke provided by the user can be the sum of the theoretical axial plunger head travel distance for dispensing the expected dose and the expected axial plunger head compression for the injection force. For example, injection stroke = theoretical axial plunger head travel distance for the target dose + expected axial plunger head compression

[0009] In the case of this exemplary manual injection device, if the total plunger head travel distance required to inject a certain dose is two millimeters, but the axial plunger head compression corresponding to the expected injection force is one millimeter, the injection stroke for delivering the target dose can be three (two plus one) millimeters. If there is space for axial rebound of the plunger, the injection needle can be removed before the rebound occurs after the injection stroke is completed. In some embodiments, the dose may be a drug pre-filled in the syringe barrel and / or a drug transferred from a vial to the syringe barrel.

[0010] The exemplary injection device may include a gear drive system that includes compound gears and is designed to reduce the injection force felt by the user. Thus, the force input by the user may be amplified, and a smaller user input force can generate a higher injection force to advance the plunger head. Such a device can also provide stability to the user in sensitive applications, such as intraocular injections. Some embodiments may not employ a gear drive system.

[0011] Unlike traditional syringe barrels, the exemplary injection device described herein may have an injection stroke that ends when the plunger rod contacts the housing of the exemplary injection device. Advancing the plunger head to the dose start position can be achieved by a ratchet mechanism that is configured to prevent the plunger rod from springing back relative to the user input when the plunger rod is axially advanced in a pre-activation step. Additionally, unlike traditional syringe barrels, the exemplary injection device may include a plunger rod locking mechanism that is configured to hold the axial position of the plunger rod at the end of the dose. This feature can ensure that the only outlet / relief path for the pressurized drug chamber is for the drug to be discharged through the needle.

[0012] According to some embodiments, an exemplary method is described herein, including: advancing a plunger rod of a syringe barrel-based drug delivery device along an axial direction of the plunger rod from a dose start position to a dose end position, thereby advancing a plunger head within the barrel of the syringe barrel-based drug delivery device to discharge a certain dose of fluid from a delivery conduit of the syringe barrel-based drug delivery device, wherein the plunger head is compressed when the plunger rod first reaches the dose end position, and the difference between the dose start position and the dose end position takes into account the compression of the plunger head due to the resistance of the fluid as it is discharged through the delivery conduit.

[0013] According to some embodiments, the dose end position is defined by the abutment of a portion of the plunger rod against the body of the syringe barrel-based drug delivery device.

[0014] According to some embodiments, the dose end position is defined by at least one of a visual marker, an audible indication, and a tactile indication.

[0015] According to certain embodiments, one end of the plunger head is mounted at one end of the plunger rod such that the end of the plunger head mounted at one end of the plunger rod travels the difference between the dose start position and the dose end position.

[0016] According to certain embodiments, the plunger head is coupled to a drive rod that is at least partially disposed within the barrel of the syringe-based drug delivery device, and the drive rod and the plunger rod are operatively coupled such that the drive rod and the plunger rod translate different amounts.

[0017] According to certain embodiments, the plunger rod is axially locked at the dose end position.

[0018] According to certain embodiments, before advancing the plunger rod of the syringe-based drug delivery device from the dose start position to the dose end position, the exemplary method may further include advancing the plunger rod to the dose start position and waiting for the fluid to stop flowing out of the delivery catheter. In certain embodiments, the exemplary method may further include indicating the dose start position of the plunger rod visually, audibly, and / or haptically.

[0019] According to certain embodiments, the plunger rod engages a ratchet that is configured to prevent the plunger rod from being pushed backward due to compression of the plunger head.

[0020] According to certain embodiments, before advancing the plunger rod of the syringe-based drug delivery device from the dose start position to the dose end position, the exemplary method may further include inserting the delivery catheter into the injection site and withdrawing the delivery catheter from the injection site before the plunger head rebounds.

[0021] According to certain embodiments, when the delivery catheter is withdrawn from the injection site, the difference between the dose start position and the dose end position of the fluid contact end of the plunger head is less than the difference between the dose start position and the dose end position of the plunger rod.

[0022] According to certain embodiments, an exemplary syringe-based drug delivery device is described herein, comprising: a housing including a barrel for containing a dose of fluid; a delivery catheter coupled to the barrel and configured to be inserted into an injection site to deliver the dose of fluid; a plunger head positioned within the barrel; a plunger rod operatively coupled to the plunger head for moving the plunger head to deliver the dose of fluid; and at least one of a visual, an audible, and a tactile indication for respectively indicating: (a) a dose start position of the plunger rod and (b) a dose end position of the plunger rod, wherein the difference between the dose start position and the dose end position takes into account compression of the plunger head during delivery of the dose of fluid.

[0023] According to certain embodiments, at least one of the visual, audible, and tactile indications of the dose end position includes an abutment between the plunger rod and the housing of the syringe-based drug delivery device that prevents further advancement of the plunger rod.

[0024] According to certain embodiments, one end of the plunger head is mounted to one end of the plunger rod such that the end of the plunger head mounted to the one end of the plunger rod travels the difference between the dose start position and the dose end position.

[0025] According to certain embodiments, the plunger head is mounted to a drive rod that is at least partially disposed within the barrel of the syringe-based drug delivery device, and the drive rod and the plunger rod are operatively coupled such that the drive rod and the plunger rod translate different amounts.

[0026] According to certain embodiments, the plunger rod engages the housing at the dose end position such that the plunger rod cannot move backward from the dose end position.

[0027] According to certain embodiments, the exemplary device may further include a ratchet configured to prevent the plunger rod from being pushed backward due to rebound of the plunger head when the plunger is advanced to the dose start position.

[0028] According to certain embodiments, when the delivery catheter is withdrawn from the injection site, the difference between the dose start position and the dose end position of the fluid contact end of the plunger head is less than the difference between the dose start position and the dose end position of the plunger rod. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0030] Figure 1 Shows an external view of a conventional syringe.

[0031] Figures 2A - 2D Shows external views of the various operating stages of a conventional syringe.

[0032] Figure 3 Shows an exploded view of an exemplary syringe-based drug delivery device that includes a mechanism for reducing the injection force felt by a user.

[0033] Figures 4A - 4E Shows external views of the various operating stages of an exemplary syringe-based drug delivery device that includes a mechanism for reducing the injection force felt by a user.

[0034] Figures 5A - 5E Shows cross-sectional views of an exemplary syringe-based drug delivery device having a plunger rod at various operating stages. The plunger rod is configured to be locked to a dose end position through a locking position.

[0035] Figure 6 Shows an external view of a mechanism for reducing the injection force felt by a user. The mechanism is part of an exemplary syringe-based drug delivery device.

[0036] Figures 7A - 7D Shows a cross-sectional view of the interaction between a dial and a drive rod of an exemplary syringe-based drug delivery device.

[0037] Figures 8A - 8C Shows a cross-sectional view of a ratchet mechanism for advancing a plunger rod and a drive rod towards a dose start position. The ratchet mechanism is part of an exemplary syringe-based drug delivery device.

[0038] Figures 9A - 9E Shows various views of a dial and a ratchet mechanism configured to be combined into one component. The dial and the ratchet mechanism are part of an exemplary syringe-based drug delivery device. Detailed Description

[0039] Now, implementations and examples of aspects of the systems and methods described herein and their variants will be described in detail. Although several exemplary variants of the systems and methods are described herein, other variants of the systems and methods may include any suitable combination of aspects of the systems and methods described herein, having combinations of all or part of the aspects.

[0040] According to various embodiments, syringe-based drug delivery devices are described herein that include mechanisms to prevent under-dosing when injecting sub-milliliter volumes of viscous injectable formulations. An exemplary syringe-based drug delivery device can include visual, audible, and / or tactile indicators to indicate when a full injection stroke has been completed. These indicators can account for the compression of the plunger stopper during the injection of the formulation, thereby providing an accurate dose rather than an under-dose.

[0041] The exemplary device can include a barrel that houses a dose of the formulation (i.e., injectable drug). One end of the barrel can lead to a needle through which the formulation can be expelled. The other end of the barrel can lead to a plunger stopper that is used to push the formulation out of the needle. The compression of the plunger stopper can be due to the resistance of the formulation as it is expelled through the needle. The plunger stopper can be operatively coupled to a plunger rod that a user can push to deliver the dose of the formulation. Since the plunger stopper may be compressible in nature, pushing the plunger rod a distance "X" may not mean that the plunger stopper moves the entire distance "X". Instead, a portion of the plunger stopper may be compressed, meaning that not all of the formulation can be expelled from the barrel through the needle (i.e., under-dosing). To deliver an accurate dose of the formulation, the plunger rod can be advanced in the axial direction through a full injection stroke, starting at a "dose start" position and ending at a "dose end" position. This in turn pushes the plunger stopper through the barrel, expelling the formulation out of the needle. When the plunger rod first reaches the "dose end" position, the plunger stopper may be compressed.

[0042] The settings of the "dose start" and "dose end" positions can account for the compression of the plunger stopper, thereby allowing a full dose of the formulation to be dispensed. As described above, the indicators can alert the user when the "dose start" and "dose end" positions are reached, allowing the user to accurately determine that the full injection stroke has been completed. In some embodiments, the device can include a dial with numbers that rotates when the plunger rod is pressed. The change in the dial numbers can correspond to specific positions of the dose.

[0043] A method of using a syringe-based drug delivery device can include advancing a plunger rod of the syringe-based drug delivery device from a dose start position to a dose end position along an axial direction of the plunger rod, thereby advancing a plunger head within a barrel of the syringe-based drug delivery device to expel a dose of fluid from a delivery conduit of the syringe-based drug delivery device, wherein the plunger head is compressed when the plunger rod first reaches the dose end position, and a difference between the dose start position and the dose end position accounts for compression of the plunger head due to resistance of the fluid as it is expelled through the delivery conduit. The dose end position can be defined by abutment between a portion of the plunger rod and a body of the syringe-based drug delivery device. The dose end position can be defined by at least one of a visual marker, an audible indication, and a tactile indication. The plunger head can be mounted at one end thereof to one end of the plunger rod such that an end of the plunger head mounted to the one end of the plunger rod travels the difference between the dose start position and the dose end position. The plunger head can be coupled to a drive rod that is at least partially disposed within the barrel of the syringe-based drug delivery device, and the drive rod and the plunger rod can be operatively coupled such that the drive rod and the plunger rod translate different amounts. The plunger rod can be axially locked at the dose end position.

[0044] Before advancing the plunger rod of the syringe-based drug delivery device from the dose start position to the dose end position, the exemplary method can further include advancing the plunger rod to the dose start position and waiting for the fluid to stop flowing out of the delivery conduit. In certain embodiments, the exemplary method can further include indicating the dose start position of the plunger rod in a visual, audible, and / or tactile manner. The plunger rod engages a ratchet configured to prevent the plunger rod from being pushed backward due to compression of the plunger head. Optionally, before advancing the plunger rod of the syringe-based drug delivery device from the dose start position to the dose end position, the exemplary method can further include inserting the delivery conduit into an injection site and withdrawing the delivery conduit from the injection site before the plunger head rebounds. When the delivery conduit is withdrawn from the injection site, a difference between a dose start position of a fluid contact end of the plunger head and a dose end position of the fluid contact end of the plunger head can be less than a difference between the dose start position and the dose end position of the plunger rod.

[0045] According to one aspect, an exemplary syringe-based drug delivery device may include: a housing including a barrel for containing a dose of fluid; a delivery catheter coupled to the barrel and configured to be inserted into an injection site to deliver the dose of fluid; a plunger head positioned within the barrel; a plunger rod operatively coupled to the plunger head for moving the plunger head to deliver the dose of fluid; and at least one of a visual, an audible, and a tactile indication for respectively indicating: (a) a dose start position of the plunger rod and (b) a dose end position of the plunger rod, wherein a difference between the dose start position and the dose end position takes into account compression of the plunger head during delivery of the dose of fluid. The at least one of the visual, audible, and tactile indication of the dose end position may include an abutment between the plunger rod and the housing of the syringe-based drug delivery device that prevents further advancement of the plunger rod.

[0046] The plunger head may be mounted at one end thereof to one end of the plunger rod such that an end of the plunger head mounted to the one end of the plunger rod travels the difference between the dose start position and the dose end position. The plunger head may be mounted to a drive rod that is at least partially disposed within the barrel of the syringe-based drug delivery device and the drive rod and the plunger rod are operatively coupled such that the drive rod and the plunger rod translate different amounts. The plunger rod may engage the housing at the dose end position such that the plunger rod cannot move backward from the dose end position. The exemplary device may further include a ratchet configured to prevent the plunger rod from being pushed backward due to rebound of the plunger head when the plunger is advanced to the dose start position. When the delivery catheter is withdrawn from the injection site, a difference between a dose start position of a fluid contact end of the plunger head and a dose end position of the fluid contact end of the plunger head may be less than a difference between the dose start position and the dose end position of the plunger rod.

[0047] In the following description of various embodiments, reference is made to the accompanying drawings which illustrate specific embodiments in which the disclosure may be practiced. It is to be understood that other embodiments and examples may be practiced and changes may be made without departing from the scope of the present disclosure.

[0048] In addition, it should be understood that the singular forms "a", "an", and "the" used in the following description are also intended to include the plural forms unless the context clearly dictates otherwise. It should also be understood that the term "and / or" as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. It should be further understood that the terms "comprises" and / or "comprising" specify the presence of the stated features, integers, steps, operations, elements, components, and / or units, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, units, and / or combinations thereof.

[0049] Certain terms are used in this specification only for convenience and reference purposes and are not limiting. For example, the words "upward", "downward", "right", and "left" refer to the directions shown in the accompanying drawings to which reference is made. The words "inward" and "outward" refer respectively to directions toward and away from the geometric center of the component and its designated part. The words "forward" and "distal" refer to the direction toward the end of the component closest to the body, and the words "backward" and "proximal" refer to the direction toward the end of the component farthest from the body. Such terms include the specifically mentioned words, their derivatives, and words of a similar nature.

[0050] Figures 2A - 2DShows the various operating phases of a syringe-based delivery system, which system includes a cylindrical syringe barrel 1. The inner surface of the syringe barrel 1 may or may not be lubricated so that the resilient plunger head 2 can be axially translated along the central axis of the syringe barrel 1 by means of a plunger rod 3 configured to be manipulated by a user. Typically, the user adjusts the position of the plunger head 2 to the dose start position by aligning a portion (e.g., the tip) of the plunger head 2 with a dose volume marking (not shown) printed on the outer surface of the syringe barrel 1. In the illustrated embodiment, the dose start position is visually indicated by a marking 12 on the plunger rod 3, which indicates that the plunger head 2 is in the dose start position when it is aligned with the proximal end of the syringe barrel 1. In some embodiments, a tactile and / or audible indication of the dose start position may be provided. For example, a protrusion on the plunger rod 3 may contact a portion of the syringe barrel 1 to provide the user with tactile feedback and / or an audible sound. An injectable drug 4 may be contained within the syringe barrel 1. Once at the dose start position, the user may wait until the injectable drug 4 stops flowing out of the needle of the needle assembly 5, which may indicate that the plunger head 2 has rebounded. For an injection using a delivery catheter (e.g., the needle assembly 5, including the needle), the user may insert the needle of the needle assembly 5 into the target injection site and axially press the plunger rod 3 until it reaches the dose end position. The dose end position may be defined by the abutment between the plunger rod 3 and the syringe barrel 1, and / or may be indicated to the user visually, audibly, and / or tactilely. In the illustrated embodiment, the plunger rod 3 includes a dose end position indication 12. When this indication 12 is aligned with the proximal end of the syringe barrel 1, it may indicate the dose start position.

[0051] In the absence of compression of the plunger head 2, the dose end position can be when the plunger head reaches the bottom of the syringe barrel 1. The distance D1 is the length of the injection stroke of the plunger rod 3 in the axial direction from the dose start position SOD to the dose end position EOD1 to dispense a sub-milliliter injection volume V.

[0052] Figure 2C Shows a syringe-based delivery system in a scenario where the plunger head 2 has been compressed by a distance D2, such that the dose end position is now EOD2. The difference between the dose end positions EOD2 and EOD1 (equal to D2) will correspond to the volume of drug that would not be dispensed (i.e., the underdose) due to the compression of the plunger head 2 if the plunger rod 3 were not further advanced and the needle assembly 5 were withdrawn from the injection site before the head rebounds. To dispense the same drug volume V corresponding to the Figure 2B scenario above (and to bring the plunger head 2 to the same dose end position EOD1), an additional injection stroke D2 is required, as shown in Figure 2DAs shown. The distance D2 is the difference along the axial direction of the plunger rod 3 between EOD1 and EOD2. Thus, when plunger head 2 compression occurs during sub-milliliter volume injection, the injection stroke for delivering a sub-milliliter injection volume V will be D1 + D2, as Figure 2D As shown. Accordingly, a syringe-based delivery system can include a visual, audible, or tactile indication of the end-of-dose position of the plunger rod 3. In the illustrated embodiment, this is in the form of a visual indication 12 on the plunger rod 3. The user can push the plunger rod 3 until the visual indication 12 aligns with the proximal end of the syringe barrel 1. Once this occurs, the full dose has been dispensed and the user can withdraw the needle from the injection site before plunger head 2 rebound occurs.

[0053] Figure 3 An exploded view of an exemplary syringe-based drug delivery device is shown, the device including a mechanism for reducing the injection force felt by the user. The device may include a cap 6-1 and a housing 6-2, which together can be regarded as the body of the device. The cap 6-1 and the housing 6-2 may include mating features configured to be fastened together. The device may include a plunger rod 10-2 and a drive rod 10-1, which interact with a compound gear 7 that can be axially constrained within the body of the device by a pin 8. The device may include a rotary ratchet 9-2 and a beam (not shown) on the housing 6-2, which can be configured to ensure that the plunger rod 10-2 and the drive rod 10-1 do not move retrogressively due to any resilience force exerted by the plunger head 2 when advanced to the start-of-dose position. The device may include a dial 9-1, which can interact with features on the drive rod 10-1 to axially advance the drive rod 10-1 (through the compound gear 7 and / or the plunger rod 10-2) towards the start-of-dose position. In some embodiments, the dial 9-1 and the rotary ratchet 9-2 may be combined into one component. In some embodiments, the drug 4 may be pre-filled in the syringe barrel 1 of the device and sealed by a plunger head 2 and an end cap 12. The syringe barrel 1 can be fixed to the body of the device (e.g., the cap 6-1 and the housing 6-2) using a clip 12. An elastic circular O-ring (or X-ring) can be placed within the body of the device to minimize rotational slip of the syringe barrel 1 relative to the device body.

[0054] Figures 4A - 4E An external view of the various stages of operation of an exemplary syringe-based drug delivery device (such as the Figure 3 device) is shown. Figure 4A A device pre-filled with the drug 4 received by the user is shown. Figure 4B Removing the end cap 12 from the syringe barrel 1 is shown. Figure 4C Attaching the needle assembly 5 to the syringe barrel 1 to replace the end cap 12 is shown. Figure 4DShows the plunger head 2 being advanced to the dose start position. Rotating the dial 9-1 will advance the plunger rod 10-2 and the drive rod 10-1, thereby advancing the plunger head 2 towards the dose start position. In some embodiments, the drive rod 10-1 may be at least partially disposed within the syringe barrel 1. The drive rod 10-1 and the plunger rod 10-2 may be coupled in an operatively connected manner such that when the dial 9-1 is rotated, the translation amounts of the drive rod 10-1 and the plunger rod 10-2 are different. In some embodiments, one end of the plunger head 2 may be mounted at one end of the plunger rod 10-2 such that the said end of the plunger head 2 travels at least a portion of the distance between the dose start position and the dose end position. In some embodiments, the dose start position and / or the dose end position may be defined by at least one of a visual marker, an auditory indication, and / or a tactile indication. In some embodiments, the plunger rod 10-2 may be axially locked at the dose end position.

[0055] At Figure 4D the dose start position shown, the printed dose amount 14 may be visible in the window 15, providing visual confirmation. At the same time, the dial 9-1 may reach a hard stop (not shown here) at the dose start position and may not be rotatable. In some embodiments, before the plunger rod 10-2 is advanced from the dose start position to the dose end position, the plunger rod 2 may remain at the dose start position until the fluid (e.g., from the drug 4) stops flowing out of the needle assembly 5. For example, once the dose start position is reached, the ratchet 9-2 may prevent the retrograde movement of the drive rod 10-1 due to the rebound of the plunger head 2. The user may wait until the drug 4 stops dripping from the needle assembly 5 after the plunger head 2 has sufficiently rebounded. Figure 4E Shows the device after reaching the dose end position. As shown, the plunger rod 10-2 may abut against the housing 6-2 of the device. At the instant of the dose end position, the plunger head 2 may still be compressed. The user may remove the needle assembly 5 from the injection site after the plunger rod 10-2 contacts the device body (e.g., the cap 6-1 and the housing 6-2). In some embodiments, the locking feature 13 may be locked into the cap 6-1 of the device (as Figure 5E shown), which may prevent the retrograde movement of the plunger rod 10-2 and the drive rod 10-1. Returning to Figure 4A and Figure 4E , the window 15 may display a printed mark 16 for visual confirmation of the dose end. The travel distance of the plunger rod 10-2 from its position shown in Figure 4D to the position of the plunger rod 10-2 shown in Figure 4E is the injection stroke; this travel distance may account for the compression of the plunger head 2. The injection stroke may be the nominal travel distance for the plunger head 2 to deliver the expected dose of the drug 4 plus the estimated compression of the plunger head 2 due to the expected injection force.

[0056] In some embodiments, the needle assembly 5 can be inserted into the injection site (e.g., the arm of a human patient) before the plunger rod 10-2 is advanced from the dose start position to the dose end position. The plunger rod 10-2 can engage a ratchet mechanism (e.g., Figures 5A - 5D ratchet 9-2) to prevent the plunger rod from being pushed backward due to the compression (i.e., rebound) of the plunger plug 2. The needle assembly 5 can be withdrawn from the injection site before the plunger plug 2 rebounds. In some embodiments, the difference between the dose start position and the dose end position at the end of the drug 4 near the plunger plug 2 may be less than the difference between the dose start position and the dose end position of the plunger rod 10-2 when the needle assembly 5 is withdrawn from the delivery site.

[0057] Figures 5A - 5E Illustrates the locking of the plunger rod 10-2 in the dose end position in an exemplary syringe-based drug delivery device (such as Figure 3 the device). Figure 5A Illustrates the device after the needle assembly 5 is attached. Figure 5B Illustrates a cross-sectional view of the device, showing the clip 12 of the device. The clip 12 may have two protrusions 22 (only one is shown), which move in the track 21 of the cap 6-1 and the housing 6-2 (not shown) to fasten the syringe 1 to the cap 601 and the housing 6-2 (i.e., the body of the device). The ratchet 9-2 can be constrained by the body of the device and attached to the dial 9-1 (e.g., locked in the helical direction and axially). Figure 5C Illustrates the device with the locking feature 13 along the plunger rod 10-2. As Figure 5C shown, the plunger rod 10-2 is near the dose end position but has not reached that position. At this position, the ramp feature of the locking feature 13 can be briefly deflected toward the axis of the plunger rod 10-2 before its entry point into the cap 6-1. Figure 5D Illustrates Figure 5C the state of the device after reaching the dose end position. As Figure 5D shown, the ramp feature of the locking feature 13 (which can be near the user) has been pushed past a step 17 on the cap 6-1. The locking feature 13 can no longer be deflected by the cap 6-1, so it can relax back to its original position (i.e., strike the surface on the cap 6-1), generating an audible indication that the dose end position has been reached. The ramp feature of the locking feature 13 can be restricted by the step 17 on the cap 6-1, thus preventing the reverse movement of the plunger rod 10-2. Figure 5E Shows the step 17, the clip 21, and the cap 6-1 in more detail.

[0058] Figure 6 Illustrates a mechanism for reducing the user's effort in operating an exemplary syringe-based drug delivery device (e.g., Figure 3The injection force felt when using the device). The user can contact and / or manipulate the plunger rod 10-2. The plunger rod 10-2 may have serrated teeth 18 that can engage with the larger gear 21 of the compound gear 7. The drive rod 10-1 may also include a row of teeth (rack) 19 that can engage with the smaller gear 20 of the compound gear 7. In some embodiments, the larger gear 21 and the smaller gear 20 may together form the compound gear 7. The ratio of the travel distance of the plunger rod 10-2 to the travel distance of the drive rod 10-1 may be equal to the ratio of the diameters of the larger gear 21 and the smaller gear 20. The ratio of the force felt by the user during reaction to the injection force may be approximately inversely proportional to the above ratio. Friction involved in the moving parts may increase the force felt by the user. In some embodiments, the damping mechanism may include an axial bonding feature 23 designed to prevent rotation of the drive rod 10-1. The protrusion 22 of the drive rod 10-1 may interact with the internal thread 24 in the dial 9-1 (as Figures 7A - 7D shown).

[0059] Figures 7A - 7D illustrates the interaction of the dial 9-1 with the drive rod 10-1 of an exemplary syringe-based drug delivery device (such as Figure 3 the device shown). Figure 7A Shows a cross-section of the device. Figure 7B , Figure 7C and Figure 7D show cross-sectional views that illustrate the state of the device when the needle (not shown) is attached, when the plunger rod 10-2 reaches the dose start position, and when the plunger rod 10-2 reaches the dose end position. The protrusion 22 of the drive rod 10-1 may interact with the internal thread of the dial 9-1 (as Figure 6 shown). When the dial 9-1 is rotated in one direction (e.g., the dose setting direction), the protrusion 22 may be axially advanced through the internal thread 24 until the protrusion closest to the user in the protrusion 22 exits the thread 24 and reaches the dose start position, as Figure 7C shown. Figure 7D Shows the position of the protrusion when the dose end position is reached.

[0060] Figures 8A - 8C illustrates the ratchet feature of an exemplary syringe-based drug delivery device (such as Figure 3 the device shown). The ratchet feature can be used when advancing the plunger rod 10-2 and the drive rod 10-1 towards the dose start position. Figure 8A Shows the rotation direction of the device and the dial 9-1. Figure 8B Shows another view of the device, where the cap 6-1 is removed to expose the ratchet 9-2 and the beam 25, which is part of the housing 6-2. Figure 8CThe ratchet design element is enlarged, showing planar surfaces that can impact the planar surface 26 on the ratchet 9-2. In some embodiments, these planar surfaces may be edges 27 that only allow rotation in the direction indicated by the arrow in Figure 8A Figure 9. The rotary dial 9-1 and / or the ratchet 9-2 can advance the drive rod 10-1 when setting the drug dose. Thus, the reverse movement of the plunger rod 10-2 and the drive rod 10-1 can be blocked by the planar surfaces represented by the planar surface 26 and the edge 27 (as shown in FIG. 9).

[0061] Figures 9A - 9E Different views of the dial 9-1 and the ratchet 9-2 are shown, and both can be combined into one component in an exemplary syringe-based drug delivery device. The bottom view shows the internal thread 24, which can direct the protrusion 22 of the drive rod 10-1 towards a position corresponding to the set dose. Once at the dose start position, the surface of the protrusion 22 closest to the user may be located on the planar surface 28. In some embodiments, the drive rod 10-1 may no longer be axially advanced, but the reverse movement of the drive rod 10-2 (and thus, the plunger rod 10-2) can be blocked by the planar surface 28. In some embodiments, the dose start position may not be affected by the rebound of the plunger plug 2. Another surface orthogonal to the surface of the protrusion 22 closest to the user can impact a planar surface (e.g., edge 29) when the user attempts to rotate the dial 9-1 in the dose-setting direction. This can prevent the dial 9-1 from rotating further, which can indicate to the user that the dose start position has been reached.

[0062] For those skilled in the art, for some applications (e.g., applications where it is not necessary to reduce the force felt by the user), the gear 7 may not be included. In such embodiments, the plunger rod 10-2 and the drive rod 10-1 can be one component (e.g., there can be only one plunger rod, and the plunger plug is mounted or otherwise coupled thereto). Removing the teeth 18 and 19, one or more features of the plunger rod 10-2 and / or the drive rod 10-1 can be combined into one rod.

[0063] In some embodiments, an external compressed gas source may be coupled to an exemplary syringe-based drug delivery device to provide the high injection force required to deliver sub-milliliter doses through a very fine injection needle (i.e., 37G or finer). In some embodiments, delivering a dose through such a device may or may not involve compression of the plunger head. The compressed gas source may be actuated by a foot pedal, which can free the doctor's hands in the case of an injection into a sensitive area (e.g., the subretinal space). In some embodiments, the device may achieve a slower injection speed than manual operation. To facilitate the transfer of the drug from the vial to the syringe, priming of the device, and delivery of the target volume from the dose start position to the dose end position, a user-selectable dial may be operable by the user. In some embodiments, the device may further include an adapter that connects the syringe-based module to the external compressed gas source. Unlike traditional syringe-based systems, the adapter may include dose reference markings to provide an indication of the injection progress without the clinician having to release their grip on the syringe.

[0064] For purposes of explanation, the foregoing description has been made with reference to specific embodiments. However, the above illustrative discussion is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations are possible in light of the above teachings. The embodiments were chosen and described in order to best explain the principles of the techniques and their practical applications. Thus, others skilled in the art can best utilize the techniques and various embodiments with various modifications, as appropriate for the particular use contemplated.

[0065] Although the present disclosure and examples have been described in full with reference to the accompanying drawings, it should be noted that various changes and modifications will become apparent to those skilled in the art. These changes and modifications should be understood to be included within the scope of the present disclosure and examples as defined by the claims. Finally, the entire disclosures of the patents and publications mentioned in this application are incorporated herein by reference.

Claims

1. A method, comprising: advancing a plunger rod of a syringe-based drug delivery device along an axial direction of the plunger rod from a dose start position to a dose end position, thereby advancing a plunger head within a barrel of the syringe-based drug delivery device to expel a dose of fluid from a delivery conduit of the syringe-based drug delivery device, wherein the plunger head is compressed when the plunger rod first reaches the dose end position, and a difference between the dose start position and the dose end position takes into account compression of the plunger head due to resistance of the fluid when being expelled through the delivery conduit.

2. The method according to claim 1, wherein, the dose end position is defined by abutment between a portion of the plunger rod and a body of the syringe-based drug delivery device.

3. The method according to claim 1 or claim 2, wherein, the dose end position is defined by at least one of a visual marker, an audible indication, and a tactile indication.

4. The method according to any one of the preceding claims, wherein, one end of the plunger head is mounted at one end of the plunger rod such that the end of the plunger head mounted at one end of the plunger rod travels the difference between the dose start position and the dose end position.

5. The method according to any one of the preceding claims, wherein, the plunger head is coupled to a drive rod, the drive rod is at least partially disposed within the barrel of the syringe-based drug delivery device, and the drive rod and the plunger rod are operatively coupled such that the drive rod and the plunger rod translate different amounts.

6. The method according to any one of the preceding claims, wherein, the plunger rod is axially locked at the dose end position.

7. The method according to any one of the preceding claims, comprising: before advancing the plunger rod of the syringe-based drug delivery device from the dose start position to the dose end position, advancing the plunger rod to the dose start position and waiting for the fluid to stop flowing out of the delivery conduit.

8. The method according to claim 7, comprising indicating the dose start position of the plunger rod in a visual, audible, and / or tactile manner.

9. The method according to any one of the preceding claims, wherein, the plunger rod engages a ratchet configured to prevent the plunger rod from being pushed backward due to compression of the plunger head.

10. The method according to any one of the preceding claims, comprising: before advancing the plunger rod of the syringe-based drug delivery device from the dose start position to the dose end position, inserting the delivery conduit into an injection site; and pulling out the delivery conduit from the injection site before the plunger head rebounds.

11. The method according to claim 10, wherein, When the delivery catheter is withdrawn from the injection site, the difference between the dose start position and the dose end position of the fluid contact end of the plunger head is less than the difference between the dose start position and the dose end position of the plunger rod.

12. An injection syringe-based drug delivery device, comprising: a housing including a barrel for containing a dose of fluid; a delivery catheter coupled to the barrel and configured to be inserted into an injection site to deliver the dose of fluid; a plunger head positioned within the barrel; a plunger rod operatively coupled to the plunger head for moving the plunger head to deliver the dose of fluid; and at least one of visual, auditory, and tactile indicia for respectively indicating: (a) the dose start position of the plunger rod and (b) the dose end position of the plunger rod, wherein the difference between the dose start position and the dose end position takes into account the compression of the plunger head during delivery of the dose of fluid.

13. The injection syringe-based drug delivery device according to claim 12, wherein the at least one of the visual, auditory, and tactile indicia of the dose end position includes an abutment between the plunger rod and the housing of the injection syringe-based drug delivery device, the abutment preventing further advancement of the plunger rod.

14. The injection syringe-based drug delivery device according to claim 12 or claim 13, wherein one end of the plunger head is mounted on one end of the plunger rod such that the end of the plunger head mounted on one end of the plunger rod travels the difference between the dose start position and the dose end position.

15. The injection syringe-based drug delivery device according to any one of claims 12-14, wherein the plunger head is mounted to a drive rod, the drive rod being at least partially disposed within the barrel of the injection syringe-based drug delivery device, and the drive rod and the plunger rod being operatively coupled such that the drive rod and the plunger rod translate different amounts.

16. The injection syringe-based drug delivery device according to any one of claims 12-15, wherein the plunger rod engages the housing at the dose end position such that the plunger rod cannot move backward from the dose end position.

17. The injection syringe-based drug delivery device according to any one of claims 12-16, comprising a ratchet configured to prevent the plunger rod from being pushed backward due to the rebound of the plunger head when the plunger is advanced to the dose start position.

18. The injection syringe-based drug delivery device according to any one of claims 12-17, wherein when the delivery catheter is withdrawn from the injection site, the difference between the dose start position and the dose end position of the fluid contact end of the plunger head is less than the difference between the dose start position and the dose end position of the plunger rod.

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