Drug delivery device and method for precise delivery of injectable medications - Patents.com

Abstract

Described herein are methods and systems for operating a syringe-based medication delivery device to expel a dose of fluid from a delivery conduit, such as a needle. The method includes advancing a plunger rod of a syringe-based medication delivery device axially along the plunger rod from a start-dose position to an end-dose position. This advances the plunger stopper within the barrel of the syringe-based medication delivery device. The plunger stopper is compressed when the plunger rod reaches the end-of-dose position for the first time. The difference between the start and end dose positions represents the compression of the plunger stopper caused by the resistance of the fluid to expulsion through the delivery conduit.

Description

[Technical Field]

[0001] The present invention relates to drug delivery devices and methods. CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 416,825, filed October 17, 2022, entitled "Novel Drug Delivery Device for Precise Delivery of Injectable Medication," the disclosure of which is incorporated herein by reference in its entirety.

[0002] Technical Field This application relates generally to injectable drug delivery devices, and more particularly to devices for the injection of sub-milliliter volumes of viscous injectable formulations.

[0003] background Syringes are commonly used to administer injectable therapeutics or fluids. As shown in Figure 1, a syringe typically consists of a cylindrical syringe barrel, an elastomeric plunger stopper that slides along the axis of the syringe barrel upon user manipulation of the plunger rod, and a needle. The plunger stopper, syringe barrel, and needle encapsulate a drug fluid chamber with a needle orifice that provides the only exit point for the drug fluid.

[0004] Increasingly, the viscosity of drug formulations is increasing due to the emergence of high-strength biologic drugs, bispecific antibody therapeutics, and long-acting formulations. The Hagen-Poiseuille equation (reproduced below) can be used to describe the relationship between the injection force (F) required during drug delivery and the viscosity (μ) of the formulation. F=128QμLA / πD 4 Q - volumetric flow rate, μ - kinematic viscosity, L - needle length, D - needle inner diameter, A - Syringe inner cross-sectional area

[0005] The Hagen-Poiseuille equation shows how increasing viscosity leads to greater injection forces, and how other parameters, such as needle inner diameter and syringe diameter, affect injection force. The Hagen-Poiseuille equation also shows that very thin needles, such as those used for subretinal injections, can increase injection forces even if the viscosity of the drug being injected is low.

[0006] In conventional syringes, the elastomeric plunger stopper is compressible. When a user advances the plunger rod to administer the drug contained in the syringe, the drug solution is pressurized and flows through the needle. For highly viscous formulations and / or when the formulation is injected through a thin-gauge needle, pressure can build up in the fluid chamber enough to cause compression of the plunger stopper even as the drug is being dispensed through the needle. Thus, some user input to inject the drug solution can cause axial compression (with radial displacement) of the plunger stopper rather than injection of the drug solution. In this case, the user's tactile feedback may indicate that injection is occurring, but in reality the user may simply be compressing the plunger. For larger volumes (milliliters), this effect (axial compression of the plunger stopper) is only a small percentage of the axial movement of the plunger stopper to administer the entire dose. However, for volumes less than 1 milliliter, the extent of axial compression of the plunger stopper can be significant relative to the axial movement of the plunger stopper to deliver the intended dose volume for highly viscous formulations and / or when the formulation is injected through a thin gauge needle. Thus, if the amount of axial user input is not representative of axial compression, the plunger stopper may not achieve the axial movement necessary to administer the full dose, and an underdose may result.

[0007] In applications where a user (e.g., a clinician) cannot visually inspect the plunger stopper during injection, such as ocular injection, the user may rely entirely on tactile sensation, which can be misleading, as in the situation described above involving submilliliter doses. Additionally, injection devices incorporating conventional syringes are designed to advance the plunger stopper axially a certain distance without considering plunger stopper compression, which can result in significant underdosing when administering submilliliter amounts of formulation. Thus, viscous formulations, submilliliter doses, and / or injection of submilliliter amounts through very thin needles can amplify the challenges of drug delivery with syringes or syringe-based systems.

[0008] overview Embodiments of the present disclosure are directed toward methods and syringe-based drug delivery device designs to address challenges in applications involving high injection forces for injecting sub-milliliter volumes. In certain embodiments, an exemplary injection device may ensure that an accurate and precise sub-milliliter dose is injected when plunger stopper compression occurs. To account for plunger stopper compression, the injection stroke provided by the user may be the sum of the theoretical axial plunger stopper travel distance to expel the expected dose and the expected axial plunger stopper compression for the injection force. For example, Injection stroke = Theoretical axial plunger stopper movement for the target dose + Expected axial plunger stopper compression

[0009] For this exemplary manual injection device, if the total plunger stopper travel to inject a dose is 2 millimeters, but the axial plunger stopper compression corresponding to the expected injection force is 1 millimeter, the injection stroke to deliver the target dose may be 3 (2 + 1) millimeters. If there is room for axial decompression of the stopper, the injection needle may be removed following completion of the injection stroke before decompression occurs. In some embodiments, the dose may be a medication pre-filled into a syringe and / or transferred from a vial to the syringe.

[0010] Exemplary injection devices may include a gear train involving compound gears configured to attenuate the injection force experienced by the user. Thus, user input forces may be amplified, and smaller user input forces may generate larger injection forces to advance the plunger stopper. Such devices may also provide stability to the user in delicate applications, such as ocular injection. In some embodiments, a gear train may not be used.

[0011] Unlike conventional syringes, the exemplary injection devices described herein may have an injection stroke that terminates when the plunger rod contacts the housing of the exemplary injection device. Advancement of the plunger stopper to the start of dose position may be achieved via a ratcheted mechanism configured to prevent the plunger rod from bouncing back in the direction opposite to user input as it is advanced axially during the priming step. Furthermore, unlike conventional syringes, the exemplary injection devices may include a plunger rod locking mechanism configured to maintain the axial position of the plunger rod at the end of the dose. This feature may ensure that the only outlet / relief for the pressurized medication chamber is for medication to flow out through the needle.

[0012] According to some embodiments, described herein is an exemplary method comprising advancing a plunger rod of a syringe-based drug delivery device in an axial direction of the plunger rod from a start of dose position to an end of dose position to advance a plunger stopper within a barrel of the syringe-based drug delivery device to expel a dose of a fluid from a delivery conduit of the syringe-based drug delivery device, wherein the plunger stopper is compressed when the plunger rod first reaches the end of dose position, and wherein the difference between the start of dose position and the end of dose position represents compression of the plunger stopper caused by resistance of the fluid to expulsion through the delivery conduit.

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

[0014] According to some embodiments, the end-of-administration location is defined by at least one of a visual marker, an audible indicator, and a tactile indicator.

[0015] According to some embodiments, the plunger stopper is attached at one end to the end of the plunger rod, and the one end of the plunger stopper attached to that end of the plunger rod moves by the difference between the start of administration position and the end of administration position.

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

[0017] According to some embodiments, the plunger rod is axially locked in the end-of-dose position.

[0018] According to some embodiments, the exemplary method may further comprise advancing the plunger rod to the start-of-dose position and waiting for the fluid to stop flowing out of the delivery conduit before advancing the plunger rod of the syringe-based drug delivery device from the start-of-dose position to the end-of-dose position. In some embodiments, the exemplary method may further comprise providing a visual, audible, and / or tactile indication of the start-of-dose position of the plunger rod.

[0019] According to some embodiments, the plunger rod engages a ratchet configured to prevent the plunger rod from being pushed back due to the compression of the plunger stopper.

[0020] According to some embodiments, the exemplary method may further comprise inserting the delivery conduit into an injection site before advancing the plunger rod of the syringe-based drug delivery device from the start administration position to the end administration position, and withdrawing the delivery conduit from the injection site before depressurizing the plunger stopper.

[0021] According to some embodiments, the difference between the start of administration position of the fluid contacting end of the plunger stopper and the end of administration position of the fluid contacting end of the plunger stopper is less than the difference between the start of administration position and the end of administration position of the plunger rod when the delivery conduit is withdrawn from the injection site.

[0022] According to some embodiments, described herein is an exemplary syringe-based drug delivery device comprising: a housing including a barrel for containing a dose of fluid; a delivery conduit coupled to the barrel, the delivery conduit configured for insertion into an injection site to deliver the dose of fluid; a plunger stopper disposed within the barrel; a plunger rod operably coupled to the plunger stopper, the plunger stopper moving to deliver the dose of fluid; and at least one of a visual, audible, and tactile indicator of (a) a start dose position of the plunger rod and (b) an end dose position of the plunger rod, respectively, wherein a difference between the start dose position and the end dose position represents compression of the plunger stopper during delivery of the dose of fluid.

[0023] According to some embodiments, at least one of the visual, audible and tactile indicators of the end-of-dose position comprises an abutment between the plunger rod and the housing of the syringe-based drug delivery device, the abutment preventing the plunger rod from being advanced further.

[0024] According to some embodiments, the plunger stopper is attached at one end to the end of the plunger rod, and the one end of the plunger stopper attached to the end of the plunger rod moves by the difference between the start administration position and the end administration position.

[0025] According to some embodiments, the plunger stopper is attached to a drive rod that is at least partially disposed within the barrel of the syringe-based medication delivery device, and the drive rod and the plunger rod are operably coupled such that the drive rod and the plunger rod move by different amounts.

[0026] According to some embodiments, the plunger rod engages the housing at the end-of-dose position such that the plunger rod cannot move rearwardly from the end-of-dose position.

[0027] According to some embodiments, the exemplary device may further comprise a ratchet configured to prevent the plunger rod from being pushed back due to decompression of the plunger stopper when the plunger rod is advanced to the start of administration position.

[0028] According to some embodiments, the difference between the start of administration position of the fluid contact end of the plunger stopper and the end of administration position of the fluid contact end of the plunger stopper is less than the difference between the start of administration position and the end of administration position of the plunger rod when the delivery conduit is withdrawn from the injection site. [Brief explanation of the drawings]

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

[0030] FIG. 1 depicts an external view of a conventional syringe.

[0031] 2A-2D (FIG. 2A to FIG. 2D) depict external views of various stages of operation of a conventional syringe.

[0032] FIG. 3 depicts an exploded view of an exemplary syringe-based drug delivery device that includes a mechanism for attenuating the injection force experienced by the user.

[0033] 4A-4E (FIG. 4A to FIG. 4E) depict external views of various stages of operation of an exemplary syringe-based drug delivery device equipped with a mechanism for attenuating the injection force experienced by a user.

[0034] 5A-5E (FIG. 5A to FIG. 5E) depict cross-sectional views of various stages of operation of an exemplary syringe-based drug delivery device having a plunger rod configured to be locked into an end-of-dosage position via a locking position.

[0035] 6 depicts an external view of a mechanism for attenuating the injection force experienced by a user, the mechanism being part of an exemplary syringe-based drug delivery device.

[0036] 7A-7D (FIGS. 7A to 7D) depict cross-sectional views of the interaction between the dial and drive rod of an exemplary syringe-based drug delivery device.

[0037] 8A-8C (FIG. 8A to FIG. 8C) depict cross-sectional views of a ratcheting mechanism that advances the plunger rod and drive rod toward a dose initiation position, the ratcheting mechanism being part of an exemplary syringe-based drug delivery device.

[0038] 9A-9E (FIG. 9A to FIG. 9E) show various views of a dial and ratchet mechanism configured to fit together into one piece, which is part of an exemplary syringe-based drug delivery device. DETAILED DESCRIPTION OF THE INVENTION

[0039] Detailed Description Reference may now be made in detail to implementations and examples of various aspects and variations of the systems and methods described herein. Although several exemplary variations of the systems and methods are described herein, other variations of the systems and methods may include those in which aspects of the systems and methods described herein are combined in any suitable manner, including combinations of all or part of the described aspects.

[0040] Described herein, according to various embodiments, is a syringe-based drug delivery device that includes a mechanism for preventing underdosing during injection of sub-milliliter amounts of viscous injectant. Exemplary syringe-based drug delivery devices can include a visual, audible, and / or tactile indicator to indicate when a full injection stroke has been completed. The indicator can represent compression of the plunger stopper during injection of the formulation, thereby providing an accurate dose instead of an underdose.

[0041] An exemplary device may include a barrel containing a dose of formulation (i.e., an injectable drug). One end of the barrel may lead to a needle through which the formulation may be expelled. The other end of the barrel may lead to a plunger stopper for forcing the formulation out of the needle. Compression of the plunger stopper may be caused by the resistance of the formulation to expulsion through the needle. The plunger stopper may be operably connected to a plunger rod that may be pressed by a user to deliver the dose of the formulation. The plunger stopper may originally be a Because the plunger rod may be compressible (by nature), pushing the plunger rod a distance "X" may not mean that the plunger stopper moves the full distance "X." Instead, a portion of the plunger stopper may be compressed in size, meaning that not all of the formulation may be forced out of the barrel through the needle (i.e., an underdose). To deliver the correct dose of formulation, the plunger rod may be advanced axially through the entire injection stroke, starting from a "start-of-dose" position and ending at an "end-of-dose" position. This, in turn, advances the plunger stopper through the barrel and forces the formulation out of the needle. The plunger stopper may be compressed when the plunger rod first reaches the "end-of-dose" position.

[0042] "Start of dose" and "end of dose" locations can be set to represent compression of the plunger stopper, which allows the entire dose of formulation to be expelled. As previously mentioned, indicators can alert the user when the "start of dose" and "end of dose" locations have been reached, allowing the user to accurately determine when a full injection stroke has been completed. In some embodiments, the device can include a numbered dial that rotates when the plunger rod is depressed. Changes in the numbers on the dial can correspond to specific positions in the dose.

[0043] A method for using a syringe-based drug delivery device may include advancing a plunger stopper within a barrel of the syringe-based drug delivery device to advance a plunger rod of the syringe-based drug delivery device axially from a start-dose position to an end-dose position to expel a dose of fluid from a delivery conduit of the syringe-based drug delivery device, wherein the plunger stopper is compressed when the plunger rod first reaches the end-dose position, and the difference between the start-dose position and the end-dose position represents compression of the plunger stopper caused by resistance of the fluid to expulsion through the delivery conduit. The end-dose position may be defined by an abutment between a portion of the plunger rod and a body of the syringe-based drug delivery device. The end-dose position may be defined by at least one of a visual marker, an auditory indicator, and a tactile indicator. The plunger stopper may be attached at one end to the end of the plunger rod, and the end of the plunger stopper attached to the end of the plunger rod moves by the difference between the start-dose position and the end-dose position. The plunger stopper can be coupled to a drive rod that is at least partially disposed within the barrel of the syringe-based medication delivery device, and the drive rod and plunger rod can be operatively coupled such that the drive rod and plunger rod move by different amounts. The plunger rod can be axially locked in an end-of-dose position.

[0044] Before advancing the plunger rod of the syringe-based drug delivery device from the start-of-dose position to the end-of-dose position, the exemplary method may further include advancing the plunger rod to the start-of-dose position and waiting for fluid to stop flowing out of the delivery conduit. In some embodiments, the exemplary method may further include providing a visual, audible, and / or tactile indication of the start-of-dose position of the plunger rod. The plunger rod may engage with a ratchet configured to prevent the plunger rod from being pushed back due to compression of the plunger stopper. Optionally, before advancing the plunger rod of the syringe-based drug delivery device from the start-of-dose position to the end-of-dose position, the exemplary method may further include inserting a delivery conduit into an injection site and withdrawing the delivery conduit from the injection site before depressurizing the plunger stopper. The difference between the start of administration position of the fluid contact end of the plunger stopper and the end of administration position of the fluid contact end of the plunger stopper may be smaller than the difference between the start of administration position and the end of administration position of the plunger rod when the delivery conduit is withdrawn from the injection site.

[0045] According to one aspect, an exemplary syringe-based medication delivery device may include a housing with a barrel for containing a dose of fluid, a delivery conduit coupled to the barrel, the delivery conduit configured for insertion into an injection site to deliver the dose of fluid, a plunger stopper disposed within the barrel, a plunger rod operably coupled to the plunger stopper and configured to move the plunger stopper to deliver the dose of fluid, and at least one of a visual, audible, and tactile indicator of (a) a start-of-dose position of the plunger rod and (b) an end-of-dose position of the plunger rod, wherein a difference between the start-of-dose position and the end-of-dose position represents compression of the plunger stopper during delivery of the dose of fluid. The at least one visual, audible, and tactile indicator of the end-of-dose position may include an abutment between the plunger rod and the housing of the syringe-based medication delivery device, the abutment preventing the plunger rod from being further advanced.

[0046] The plunger stopper may be attached at one end to the end of the plunger rod, the end of the plunger stopper moving by a difference between a start-of-dosing position and an end-of-dosing position. The plunger stopper may be attached to a drive rod at least partially disposed within the barrel of the syringe-based drug delivery device, the drive rod and the plunger rod being operably coupled so that the drive rod and the plunger rod move by different amounts. The plunger rod may engage with the housing at the end-of-dosing position to prevent the plunger rod from moving backward from the end-of-dosing position. Exemplary devices may further include a ratchet configured to prevent the plunger rod from being pushed back due to decompression of the stopper when the plunger rod is advanced to the start-of-dosing position. The difference between the start-of-dosing position of the fluid-contacting end of the plunger stopper and the end-of-dosing position of the fluid-contacting end of the plunger stopper may be smaller than the difference between the start-of-dosing position and the end-of-dosing position of the plunger rod when the delivery conduit is withdrawn from the injection site.

[0047] In the following description of various embodiments, reference is made to the accompanying drawings, in which is shown by way of illustration specific embodiments which can be practiced. It is understood that other embodiments and examples can be made or modified without departing from the scope of the disclosure.

[0048] Additionally, as used in the following description, the singular forms "a," "an," and "the" are understood to be intended to include the plural forms as well, unless the context clearly dictates otherwise. The term "and / or," as used herein, is also understood to refer to and include any and all possible combinations of one or more of the associated listed items. Furthermore, it is also understood that the terms "comprise," "including," "comprising," and / or "comprising," when used herein, specify the presence of claimed 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 groups thereof.

[0049] Certain terms are used in this description for convenience and reference only and are not limiting. For example, the words "upper," "lower," "right," and "left" refer to directions in the drawings to which reference is made. The words "inward" and "outward" refer to directions toward and away from, respectively, the geometric center of the arrangement and its designated portion. The words "forward" and "far" refer to directions toward the end of the arrangement closest to the object, and the terms "rearward" and "near" refer to directions toward the end of the arrangement farthest from the object. This term includes the specifically mentioned words, derivatives thereof, and words of a similar nature.

[0050] 2A-2D depict various stages of operation of a syringe-based delivery system including a cylindrical syringe barrel 1. The syringe barrel 1 may or may not be lubricated on its internal surface to allow elastomeric plunger stopper 2 to move axially along the central axis of the syringe barrel 1 using a plunger rod 3 configured to be manipulated by a user. Typically, a user adjusts the location of the plunger stopper 2 to a start-of-dosing position by aligning a portion (e.g., the tip) of the plunger stopper 2 with a dosage scale (not shown) printed on the outer surface of the syringe barrel 1. In the depicted embodiment, the start-of-dosing position is visually indicated by a marker 12 on the plunger rod 3, which indicates that the plunger stopper 2 is in the start-of-dosing position when aligned with the proximal end of the syringe barrel 1. In some embodiments, a tactile and / or audible indicator of the start-of-dosing position may be provided. For example, a protrusion on the plunger rod 3 may contact a portion of the syringe barrel 1 to provide tactile feedback and / or an audible sound to the user. The injection agent 4 may be contained within the syringe barrel 1. Once at the start-of-administration position, the user may wait until the injection agent 4 stops flowing out of the needle of the needle assembly 5, which may indicate that the plunger stopper 2 has been depressurized. For injections involving a delivery conduit (e.g., a needle-containing needle assembly 5), the user may insert the needle of the needle assembly 5 into the target injection site and axially depress the plunger rod 3 until it reaches the end-of-administration position. The end-of-administration position may be defined by an abutment between a portion of the plunger rod 3 and the syringe barrel 1 and / or may be indicated to the user visually, audibly, and / or tactilely. In the depicted embodiment, an end-of-administration position indicator 12 is provided on the plunger rod 3. Alignment between this indicator 12 and the proximal end of the syringe barrel 1 may indicate the starting point for administration.

[0051] In the absence of compression of the plunger stopper 2, the end-of-dosing position may be when the plunger stopper reaches the bottom of the syringe barrel 1. Distance D1 is the length of the injection stroke along the axial direction of the plunger rod 3 as it moves from the start-of-dosing position SOD to the end-of-dosing position EOD1 to expel an injection volume V of less than 1 milliliter.

[0052] FIG. 2C depicts a syringe-based delivery system in a scenario in which the plunger stopper 2 has been compressed a distance D2 such that the end-of-dose position is now EOD2. The difference between the end-of-dose positions EOD2 and EOD1 (equal to D2) may correspond to the amount of medication that would not be dispensed (i.e., an underdose) due to compression of the plunger stopper 2 if the plunger rod 3 were not further advanced and the needle of the needle assembly 5 were withdrawn from the injection site before the stopper was depressurized. To dispense the same volume V of medication corresponding to the scenario in FIG. 2B (and to have the plunger stopper 2 reach the same end-of-dose position EOD1), an additional injection stroke D2 is required, as depicted in FIG. 2D. Distance D2 is the difference between EOD1 and EOD2 along the axial direction of the plunger rod 3. Thus, when compression of the plunger stopper 2 occurs during injection of a sub-milliliter volume, the injection stroke to deliver the sub-milliliter injection volume V may be D1 + D2, as depicted in FIG. 2D. Thus, the syringe-based delivery system may include a visual, audible, or tactile indicator of the end-of-dose position of the plunger rod 3. In the depicted embodiment, this is in the form of a visual indicator 12 on the plunger rod 3. The user may depress the plunger rod 3 until the visual indicator 12 aligns with the proximal end of the syringe barrel 1. Once this occurs, the full dose has been expelled and the user may withdraw the needle from the injection site before decompression of the plunger stopper 2 occurs.

[0053] FIG. 3 depicts an exploded view of an exemplary syringe-based drug delivery device equipped with a mechanism for attenuating the injection force experienced by a user. The device may include a cover 6-1 and a housing 6-2, both of which may collectively be considered the body of the device. The cover 6-1 and the housing 6-2 may include mating features configured to securely connect to one another. The device may include a plunger rod 10-2 and a drive rod 10-1, which interact with a compound gear 7, which may be axially constrained within the body of the device by a pin 8. The device may include a rotational ratchet 9-2 along with a beam (not shown) on the housing 6-2, which may be configured to ensure that the plunger rod 10-2 and the drive rod 10-1 do not experience retrograde travel from any decompression force exerted by the plunger stopper 2 as they advance to the start of delivery position. The device may include a dial 9-1 that may interact with a mechanism on the drive rod 10-1 to axially advance the drive rod 10-1 (via the compound gear 7 and / or plunger rod 10-2) toward a dose start position. In some embodiments, the dial 9-1 and rotational ratchet 9-2 may be combined into a single component. In some embodiments, the medication 4 may be pre-loaded into the syringe barrel 1 of the device and enclosed by the plunger stopper 2 and tip cap 12. The syringe barrel 1 may be secured to the device body (e.g., the cover 6-1 and housing 6-2) using clips 12. A circular elastomeric O-ring (or X-ring) may be positioned within the device body to minimize rotational slippage of the syringe barrel 1 relative to the device body.

[0054] 4A-4E show external views of various stages of operation of an exemplary syringe-based medication delivery device, such as the device of FIG. 3. FIG. 4A depicts the device once pre-filled with medication 4 and received by a user. FIG. 4B depicts removal of tip cap 12 from syringe barrel 1. FIG. 4C depicts installation of needle assembly 5 to syringe barrel 1 in place of tip cap 12. FIG. 4D depicts advancement of plunger stopper 2 to a start-of-dose position. Rotation of dial 9-1 advances plunger rod 10-2 and drive rod 10-1, which, in turn, advances plunger stopper 2 toward a start-of-dose position. In some embodiments, drive rod 10-1 can be at least partially disposed within syringe barrel 1. Drive rod 10-1 and plunger rod 10-2 can be operatively coupled such that drive rod 10-1 and plunger rod 10-2 move different amounts when dial 9-1 is rotated. In some embodiments, one end of the plunger stopper 2 can be attached to the end of the plunger rod 10-2 such that the end of the plunger stopper 2 moves at least a portion of the distance between the start and end of the dose position. In some embodiments, the start and / or end of the dose position can be defined by at least one of a visual marker, an audible indicator, and / or a tactile indicator. In some embodiments, the plunger rod 10-2 can be axially locked at the end of the dose position.

[0055] At the start-of-dose position shown in FIG. 4D, 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) at the start-of-dose position and may not rotate. In some embodiments, the plunger rod 10-2 may be held at the start-of-dose position until fluid (e.g., medication 4) stops flowing out of the needle assembly 5 before advancing the plunger rod 10-2 from the start-of-dose position to the end-of-dose position. For example, once the start-of-dose position is reached, the ratchet 9-2 may prevent the drive rod 10-1 from moving backward as the plunger stopper 2 depressurizes. The user may wait until the medication 4 stops dripping from the needle assembly 5 once the plunger stopper 2 has sufficiently depressurized. FIG. 4E depicts the device after the end-of-dose position has been reached. As shown, the plunger rod 10-2 may bottom out against the device housing 6-2. Just after the end-of-dose position, the plunger stopper 2 may still be compressed. The user can remove the needle assembly 5 from the injection site after the plunger rod 10-2 contacts the device body (e.g., the cover 6-1 and housing 6-2). In some embodiments, a locking mechanism 13 can lock the device cover 6-1 (as shown in FIG. 5E), which can prevent reverse movement of the plunger rod 10-2 and drive rod 10-1. Referring back to FIGS. 4A and 4E, a window 15 can display a printed mark 16 to visually confirm the end of administration. The movement of the plunger rod 10-2 from its position shown in FIG. 4D to the position shown for the plunger rod 10-2 in FIG. 4E is the injection stroke; this movement can account for the compression of the plunger stopper 2. The injection stroke can be the nominal travel of the plunger stopper 2 to deliver the intended dose of medication 4, plus the estimated compression of the plunger stopper 2 given the expected injection force.

[0056] In some embodiments, the needle assembly 5 can be inserted into an injection site (e.g., a human patient's arm) before advancing the plunger rod 10-2 from a start-of-dose position to an end-of-dose position. The plunger rod 10-2 can engage a ratchet mechanism, such as ratchet 9-2 in FIGS. 5A-5D , to prevent the plunger rod from being pushed back in response to compression (i.e., decompression) of the plunger stopper 2. The needle assembly 5 can be withdrawn from the injection site before decompression of the plunger stopper 2. In some embodiments, the difference between the start-of-dose and end-of-dose positions of the end of the plunger stopper 2 proximal to the medicament 4 can be less than the difference between the start-of-dose and end-of-dose positions of the plunger rod 10-2 when the needle assembly 5 is withdrawn from the delivery site.

[0057] 5A-5E depict an exemplary syringe-based drug delivery device, such as the device of FIG. 3, with the plunger rod 10-2 locked in the end-of-dose position. FIG. 5A shows the device after the needle assembly 5 has been attached. FIG. 5B depicts a cross-sectional view of the device exposing the device's clip 12. The clip 12 may have two protrusions 22 (only one shown) that travel within a track 21 in the cover 6-1 and within the housing 6-2 (not shown) to secure the syringe 1 to the cover 601 and the housing 6-2 (i.e., the device's body). The ratchet 9-2 may be constrained by the device's body and attached to the dial 9-1 (e.g., may be rotationally and axially locked). FIG. 5C depicts a device with a locking mechanism 13 along the plunger rod 10-2. As shown in FIG. 5C, the plunger rod 10-2 is near the end-of-dose position but has not yet reached it. In this position, the ramp feature of the locking mechanism 13 may be briefly deflected toward the axis of the plunger rod 10-2 by the entry point in the cover 6-1. FIG. 5D depicts the device of FIG. 5C after it has reached the end-of-dose position. As shown in FIG. 5D, the ramp feature of the locking mechanism 13, which may be closer to the user, is pushed past a step 17 on the cover 6-1. The locking mechanism 13 may no longer be deflected by the cover 6-1 and may thus ease toward its home position (i.e., impact the surface of the cover 6-1), generating an audible indication that the end-of-dose position has been reached. The ramp feature of the locking mechanism 13 may be limited by the step 17 on the cover 6-1, which may prevent reverse movement of the plunger rod 10-2. FIG. 5E depicts the step 17, clip 21, and cover 6-1 in more detail.

[0058] FIG. 6 depicts a mechanism for damping the injection force experienced by a user when operating an exemplary syringe-based medication delivery device, such as the device of FIG. 3 . The user may feel and / or manipulate the plunger rod 10-2. The plunger rod 10-2 may have sawtooth patterned teeth 18 that may mesh with the larger gear 21 of the compound gear 7. The drive rod 10-1 may also include a rack of teeth 19 that may mesh with the smaller gear 20 of the compound gear 7. In some embodiments, the larger gear 21 and the smaller gear 20 together may comprise the compound gear 7. The ratio of the movement of the plunger rod 10-2 to the movement 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 forces experienced by the user in response to an injection input may be approximately the reciprocal of this ratio. Frictional forces associated with the moving parts may add to the force experienced by the user. In some embodiments, the damping mechanism can include an axial keying feature 23 configured to prevent rotation of the drive rod 10-1. Protrusions 22 on the drive rod 10-1 can interact with internal threads 24 on the dial 9-1 (as shown in FIGS. 7A-7D).

[0059] 7A-7D illustrate the interaction of the dial 9-1 with the drive rod 10-1 of an exemplary syringe-based drug delivery device, such as the device of FIG. 3. FIG. 7A depicts a cross-section of the device. FIGS. 7B, 7C, and 7D depict cross-sectional views showing the state of the device once a needle (not shown) is attached, once the plunger rod 10-2 has reached the start-of-dose position, and once the plunger rod 10-2 has reached the end-of-dose position, respectively. The protrusion 22 of the drive rod 10-1 may interact with the internal threads of the dial 9-1 (as shown in FIG. 6). When the dial 9-1 is turned in one direction (e.g., the dose-setting direction), the protrusion 22 is advanced axially by the internal threads 24 until the protrusion of the protrusion 22 closest to the user exits the threads 24, and the start-of-dose position is reached, as shown in FIG. 7C. FIG. 7D depicts the position of the protrusion when the end-of-dose position is reached.

[0060] 8A-8C depict a ratchet mechanism of an exemplary syringe-based drug delivery device, such as the device of FIG. 3. The ratchet mechanism can be used to advance the plunger rod 10-2 and drive rod 10-1 toward a dose start position. FIG. 8A depicts the direction of rotation of the device and dial 9-1. FIG. 8B depicts another view of the device with the cover 6-1 removed to expose the ratchet 9-2 and beam 25 that is part of the housing 6-2. The ratchet design element is enlarged in FIG. 8C, showing planes 26 that can impinge against the plane of the ratchet 9-2. In some embodiments, these planes can be edges 27 that allow rotation only in the direction indicated by the arrow in FIG. 8A. Rotating the dial 9-1 and / or ratchet 9-2 can advance the drive rod 10-1 during drug dose setting. Thus, retrograde movement of plunger rod 10-2 and drive rod 10-1 may be prevented by the planes represented by plane 26 and edge 27 (as shown in FIG. 9).

[0061] 9A-E show different views of the dial 9-1 and ratchet 9-2, which may be combined as a single component in an exemplary syringe-based drug delivery device. The bottom diagram shows the internal threads 24 that may guide the protrusion 22 of the drive rod 10-1 toward a position corresponding to the set dose. Once in the start-of-dose position, the surface of the protrusion 22 closest to the user may rest on flat surface 28. In some embodiments, the drive rod 10-1 may no longer advance axially; however, the drive rod 10-2 (and thus the plunger rod 10-2) may be prevented from moving backward by flat surface 28. In some embodiments, the start-of-dose position may not be affected by decompression of the plunger stopper 2. When the user attempts to turn the dial 9-1 in the dose-setting direction, another surface perpendicular to the surface of the protrusion 22 closest to the user may collide with a flat surface (e.g., edge 29). This may prevent further rotation of the dial 9-1 and indicate to the user that the start-of-dose position has been reached.

[0062] It will be apparent to those skilled in the art that in certain applications (e.g., applications that do not require attenuation of the force experienced by the user), gear 7 may not be included. In such an embodiment, plunger rod 10-2 and drive rod 10-1 may be a single component (e.g., there may be only one plunger rod to which a plunger stopper is attached or otherwise coupled). With the exception of teeth 18 and 19, one or more features of plunger rod 10-2 and / or drive rod 10-1 may be coupled as a single rod.

[0063] In some embodiments, an external compressed gas source can be connected to an exemplary syringe-based drug delivery device to provide the device with the high injection forces necessary to deliver submilliliter doses through very small injection needles (i.e., 37G or smaller). In some embodiments, dose delivery through such devices may or may not involve compression of a plunger stopper. The compressed gas source can be activated using a foot pedal, freeing the clinician's hands for injections into sensitive areas such as the subretinal space. In some embodiments, the device can allow for slower injection rates than would be possible manually. A user-selectable dial can be operated by the user to facilitate transferring medication from the vial to the syringe, priming the device, and enabling delivery of a targeted volume from a start point to an end point. In some embodiments, the device can further include an adapter that connects the syringe-based module to an external compressed gas source. Unlike conventional syringe-based systems, the adapter may include dose reference markings to provide an indication of injection progress without the clinician having to loosen their grip on the syringe.

[0064] The foregoing description has been set forth with reference to specific embodiments for purposes of explanation. However, the illustrative discussion above is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of the above teachings. The embodiments were chosen and described to best explain the principles of the technology and their practical application. Those skilled in the art will thereby be able to best utilize the technology and various embodiments, with various modifications as adapted to the particular use contemplated.

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

Claims

1. 1. A method comprising advancing a plunger stopper within a barrel of a syringe-based drug delivery device to advance a plunger rod of the syringe-based drug delivery device in an axial direction of the plunger rod from a start-of-dosing position to an end-of-dosing position to expel a dose of fluid from a delivery conduit of the syringe-based drug delivery device, wherein the plunger stopper is compressed when the plunger rod first reaches the end-of-dosing position, and the difference between the start-of-dosing position and the end-of-dosing position represents compression of the plunger stopper caused by resistance of the fluid to expulsion through the delivery conduit.

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

3. 10. The method of claim 1, wherein the end-of-administration location is defined by at least one of a visual marker, an audible indicator, and a tactile indicator.

4. 2. The method of claim 1, wherein the plunger stopper is attached at one end to the end of the plunger rod, and the one end of the plunger stopper attached to the end of the plunger rod moves by the difference between the administration start position and the administration end position.

5. 10. The method of claim 1, wherein the plunger stopper is coupled to a drive rod that is at least partially disposed within the barrel of the syringe-based medication delivery device, and the drive rod and the plunger rod are operably coupled such that the drive rod and the plunger rod move by different amounts.

6. 10. The method of claim 1, wherein the plunger rod is axially locked in the end-of-dose position.

7. 2. The method of claim 1, comprising advancing the plunger rod of the syringe-based drug delivery device to the start-of-administration position and waiting for the fluid to stop flowing out of the delivery conduit before advancing the plunger rod of the syringe-based drug delivery device from the start-of-administration position to the end-of-administration position.

8. 8. The method of claim 7, comprising providing a visual, audible and / or tactile indication of the start of dose position of the plunger rod.

9. 2. The method of claim 1, wherein the plunger rod engages a ratchet configured to prevent the plunger rod from being forced backward due to the compression of the plunger stopper.

10. 2. The method of claim 1, inserting the delivery conduit into an injection site before advancing the plunger rod of the syringe-based medication delivery device from the start-of-administration position to the end-of-administration position; withdrawing the delivery conduit from the injection site prior to depressurizing the plunger stopper.

11. 11. The method of claim 10, wherein a difference between a start of administration position of the fluid contact end of the plunger stopper and an end of administration position of the fluid contact end of the plunger stopper is less than a difference between the start of administration position and the end of administration position of the plunger rod when the delivery conduit is withdrawn from the injection site.

12. 1. A syringe-based drug delivery device comprising: a housing comprising a barrel for containing a dose of fluid; a delivery conduit coupled to the barrel, the delivery conduit configured for insertion into an injection site to deliver the dose of the fluid; a plunger stopper disposed within the barrel; a plunger rod operatively coupled to the plunger stopper to move the plunger stopper to deliver the dose of the fluid; and (b) at least one of a visual, an audible, and a tactile indicator of a respective start-of-dose position of the plunger rod and an end-of-dose position of the plunger rod; a difference between the start dose position and the end dose position representing compression of the plunger stopper during delivery of the dose of the fluid; Syringe-based drug delivery devices.

13. 13. The syringe-based drug delivery device of claim 12, wherein the at least one of the visual, audible, and tactile indicators of the end-of-administration position comprises an abutment between the plunger rod and a housing of the syringe-based drug delivery device, the abutment preventing the plunger rod from being advanced further.

14. 13. A syringe-based drug delivery device as described in claim 12, wherein the plunger stopper is attached at one end to the end of the plunger rod, and the one end of the plunger stopper attached to the end of the plunger rod moves by the difference between the administration start position and the administration end position.

15. 13. The syringe-based medication delivery device of claim 12, wherein the plunger stopper is attached to a drive rod that is at least partially disposed within the barrel of the syringe-based medication delivery device, and the drive rod and the plunger rod are operably coupled such that the drive rod and the plunger rod move by different amounts.

16. 13. The syringe-based medication delivery device of claim 12, wherein the plunger rod engages with the housing at the end-of-dosing position such that the plunger rod cannot move rearward from the end-of-dosing position.

17. 13. The syringe-based medication delivery device of claim 12, further comprising a ratchet configured to prevent the plunger rod from being pushed back due to decompression of the plunger stopper when the plunger rod is advanced to the administration start position.

18. 13. The syringe-based drug delivery device of claim 12, wherein the difference between the administration start position of the fluid contact end of the plunger stopper and the administration end position of the fluid contact end of the plunger stopper is less than the difference between the administration start position and the administration end position of the plunger rod when the delivery conduit is withdrawn from the injection site.

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