Variable dose syringe

Abstract

The invention relates to a variable dose syringe comprising a dose setter operably coupled to a plunger rod and comprising a rotatable body comprising a set of one or more stops, and one or more retainers for engaging the set of one or more protrusions of the plunger rod according to at least a rotational position of the set of one or more retainers relative to the set of one or more protrusions, wherein a first rotational adjustment device associated with the dose setter is configured to set a first dose increment by adjusting a relative axial position between the rotatable body and the plunger rod, and a second rotational adjustment device associated with the dose setting assembly is configured to set a second dose increment greater than the first dose increment by adjusting a relative rotational alignment between the set of one or more stoppers and the set of one or more protrusions.

Description

[0001] This invention application is a divisional application based on an invention patent application with an application date of November 13, 2020, application number 202080092499.7 (international application number PCT / US2020 / 060589) and name “Variable Dose Syringe”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 62 / 935,193, filed on November 14, 2019, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0004] The present disclosure relates generally to drug delivery devices and, more particularly, to dosing systems for prefilled syringes. Background Art

[0005] Syringes are commonly used to administer injectable therapeutic agents or fluids. Syringes are usually composed of a cylindrical barrel, and the inner surface of the barrel is lubricated to enable the elastic plunger stop to be axially manipulated with the plunger rod. Considering the intended application, several types of syringes are designed. Some syringes can also be used to store injectable drugs within a few months; these involve special construction materials of syringes, including syringes without lubricants. Syringes designed for storing drugs are called prefillable syringes (PFS). Some syringes have injection needles pre-attached to the syringe barrel, while some other syringes have a Luer lock feature to connect to other delivery catheters, such as catheters, injection ports, etc. Dose marks are printed on the outer surface of some syringe barrels as a reference for users to set doses; this is conventional dose metering.

[0006] Dosage metering allows different amounts of a drug (e.g., drug doses) to be administered by simply changing the volume of the drug for a given concentration of the drug. The need to administer different drug doses (i.e., dosage metering) is driven by many factors; for example, in tumor treatment, dosage metering helps administer a certain amount of drug based on the patient's weight. Another illustrative example is the injection of insulin, where the amount of insulin injected is based on the patient's blood glucose level.

[0007] Most drugs have a therapeutic window that maximizes drug efficacy. The amount of drug administered at a level below the therapeutic window can result in suboptimal efficacy of the drug, and conversely, the amount of drug administered at a level exceeding the limit of the therapeutic window can expose the patient to the toxic effects of the drug. The accuracy and precision of drug dose delivery are important for ensuring the best therapeutic outcome for a given drug. For sub-milliliter injection volumes, the accuracy and precision of drug delivery are more challenging. In the case of applications involving treatment of pediatric patients, injection of highly effective therapeutic agents (e.g., insulin, tumor agents, immunotherapy, etc.), targeted organ delivery (e.g., eyes, brain, inner ear, etc.), injection of sub-milliliter volumes is relevant.

[0008] Consistent with the need for accurate, precise drug delivery, there is a need to minimize the number of SKUs (stock keeping units) that drug manufacturers must maintain in order to simplify the supply chain logistics of drugs that need to be metered for the reasons mentioned above. Each drug SKU has overhead associated with formulation development, regulatory approval, testing, manufacturing, storage, customer support, etc. Maintaining multiple SKUs of the same drug will have inherent redundancy, which results in increased costs to provide the drug to patients.

[0009] Conventional dose metering using current syringes has limitations on the volume range of a given syringe and is inaccurate and imprecise for administering microliter-sized volumes. Conventional syringes are also limited in the availability of features that maximize the safety of drug administration, e.g., needle stick prevention, counterfeit prevention, prevention of abuse of unused drugs, etc.

[0010] Injection devices also need to incorporate needle safety to mitigate the risk of needle stick injuries in order to comply with regulations or ensure suitability for administration in a home setting. Activation of the needle safety should be independent of the dose volume injected. Moreover, it is important to prevent premature activation of the needle safety mechanism which could result in non-therapeutic or underdosing.

[0011] Pen injectors have been widely used to inject insulin. Pen injectors allow the user to select a dose (injection volume) and self-administer the drug. There are some limitations to the widespread applicability of pen injectors - a) pen injectors include a cartridge (rather than a syringe), b) they require a dedicated injection needle, c) are designed for multiple uses, d) the maximum injection volume that can actually be delivered is about 1 mL, e) needle safety is not included.

[0012] In any injectable dose delivery system comprising a cylindrical barrel (syringe or cartridge), the volume of the injected dose is defined by the difference between the dose start position of the plunger stop and the dose end position of the plunger stop (see Figure 1). Errors in dose volume are caused by variability in setting the above-mentioned dose start position and / or variability caused by the dose end position. This variability ultimately translates into inaccuracy and imprecision in the final dose volume delivered. Sources of this variability include user error and / or tolerances of delivery system components.

[0013] Manually operated traditional dose delivery systems can deliver a certain range of volumes. All manually operated traditional injectable dose delivery systems use the same volume resolution to set the dose volume, regardless of whether the dose volume is selected at the lower end of the delivery volume range or the upper end of the delivery volume range. This results in limiting the maximum deliverable volume of the device (e.g., pen-type syringe) with higher injection volume resolution, or causes the inaccuracy and imprecise (e.g., traditional subcutaneous syringe and prefilled syringe) of low volume (microliter range). Simply increasing the volume range of the above-mentioned higher resolution device will cause the overall size of the device to be increased to a degree that makes it impractical. Similarly, large volume devices (e.g., 5 milliliters of maximum volume syringes) will not be suitable for delivering small volumes (e.g., 10 microliter doses). When used, there is a compromise between dose volume resolution and volume range in the prior art of manually operated drug delivery systems.

[0014] The outer diameter of the elastic plunger stop is slightly oversized relative to the inner diameter of the syringe - this helps to form a seal in pre-filled syringes and non-pre-filled syringes. After the plunger stop is inserted into the syringe, and during storage, the plunger stop continues to apply a radially outward force to the inner diameter of the syringe barrel, thereby generating "static friction". After long-term storage of such pre-filled syringes, additional effort is required to overcome the static friction in order to loosen the plunger stop from its original position. The user force applied axially is generally referred to as the "loosening" force. Overcoming static friction with the loosening force causes the user to temporarily lose control of the plunger rod stroke. If a priming step is required before injection, the consequences of this loss of control are particularly serious. Priming is important to ensure the patency of the delivery catheter (e.g., needle). Priming will help minimize the risk of air being delivered as part of the injection, and therefore minimize underdosing. Over-priming results in exceeding the minimum volume required to perform the priming step, which can lead to potential underdosing of the maximum dose and / or drug waste. Overcoming the static friction of the plunger stop is uncomfortable for the user. Summary of the invention

[0015] According to various embodiments, a plunger rod assembly for a syringe includes fine and coarse dose setting capabilities. The syringe may include one or more dials for achieving fine dose setting and for achieving coarse dose setting. According to various embodiments, the dose delivery starting position of the plunger rod of the plunger rod assembly that pushes the stopper in the syringe barrel to deliver the dose is the same, regardless of the dose setting, and the dose setting end point for controlling the stop position of the plunger rod is different for different doses. According to various embodiments, one or more rotational inputs can achieve fine dose setting and coarse dose setting. In some embodiments, different dials are used as user inputs for fine and coarse dose settings, while in other embodiments, the same dial is used as user input for fine and coarse dose settings.

[0016] According to various embodiments, a plunger rod assembly for a syringe includes: a body; a plunger rod, which is at least partially received in the body and includes a set of one or more protrusions; and a dose setter, which is operably coupled to the plunger rod and includes a rotatable body, the rotatable body including a set of one or more stops for engaging the set of one or more protrusions of the plunger rod at least according to a rotational position of the set of one or more stops relative to the set of one or more protrusions, wherein a first rotational adjustment device associated with the dose setter is configured to set a first dose increment by adjusting the relative axial position between the rotatable body and the plunger rod, and a second rotational adjustment device associated with the dose setting assembly is configured to set a second dose increment greater than the first dose increment by adjusting the relative rotational alignment between the set of one or more stops and the set of one or more protrusions.

[0017] In any of these embodiments, the first rotation adjustment device may include a rotatable dial that engages the rotatable body and can rotate relative to the rotatable body to axially translate the rotatable body relative to the main body. In any of these embodiments, the rotatable dial may include threads that engage threads of the rotatable body.

[0018] In any of these embodiments, the second rotation adjustment device may include a dial for rotating the rotatable body. In any of these embodiments, the rotatable body may translate relative to the dial. In any of these embodiments, the rotatable body and the dial may be fixed relative to each other.

[0019] In any of these embodiments, the first rotation adjustment device can adjust the axial position of the rotatable body relative to the main body.

[0020] In any of these embodiments, the first rotational adjustment device can adjust the axial position of the plunger rod relative to the body.

[0021] In any of these embodiments, the plunger rod may be rotationally fixed.

[0022] In any of these embodiments, the rotatable body may be laterally offset relative to the plunger rod.

[0023] In any of these embodiments, the rotational axis of the rotatable body may intersect the plunger rod.

[0024] In any of these embodiments, the set of one or more protrusions may include a single protrusion and the set of one or more stops may include a plurality of stops.

[0025] In any of these embodiments, the set of one or more protrusions may include a plurality of protrusions and the set of one or more stops may include a single stop.

[0026] In any of these embodiments, the first rotation adjustment device may include a slot in the rotatable body that receives a portion of the plunger rod, and the slot includes an inclined surface that axially pushes the portion of the plunger rod received in the slot when the rotatable body rotates. In any of these embodiments, the set of one or more protrusions may include a single protrusion, and the portion of the plunger rod is a single protrusion. In any of these embodiments, the portion of the plunger rod can be disengaged from one circumferential end of the slot so that continued rotation of the rotatable body does not cause further axial translation of the plunger rod relative to the rotatable body.

[0027] According to various embodiments, a plunger rod assembly includes: a body; a plunger rod at least partially received in the body and including one or more protrusions; and a dose setter including a rotatable body including one or more first stops aligned with the one or more protrusions to define a dose delivery end position of the plunger rod, wherein different alignments of the one or more first stops with the one or more first protrusions define different dose settings, and a second stop engaging the one or more protrusions of the plunger rod to define a dose delivery start position of the plunger rod, wherein the dose delivery start position of the plunger rod is the same for different dose settings.

[0028] In any of these embodiments, the one or more protrusions of the plunger rod may include a first protrusion, and wherein engagement between the first protrusion and the second stop defines a dose delivery start position, and engagement between the first protrusion and the one or more first stops defines a dose delivery end position.

[0029] In any of these embodiments, one or more protrusions of the plunger rod may include a first protrusion and a second protrusion, and the engagement between the first protrusion and the second stop defines a dose delivery start position, and the engagement between the second protrusion and one or more first stops defines a dose delivery end position.

[0030] In any of these embodiments, the second stop may include a slot for receiving the first protrusion of one or more protrusions.

[0031] In any of these embodiments, the slot may include an inclined surface that pushes the first protrusion received in the slot when the rotatable body rotates in the rotation direction.

[0032] In any of these embodiments, when the rotatable body continues to rotate in the rotation direction, the first protrusion may disengage from the slot.

[0033] In any of these embodiments, the dose setter may include a rotatable dial that engages the rotatable body and may rotate relative to the rotatable body to axially translate the rotatable body relative to the body.

[0034] In any of these embodiments, the rotatable dial may include threads that engage the threads of the rotatable body.

[0035] In any of these embodiments, the dose setter may include a dial for rotating the rotatable body.

[0036] In any of these embodiments, the rotatable body may translate relative to the dial.

[0037] In any of these embodiments, the rotatable body and the dial may be fixed relative to each other.

[0038] In any of these embodiments, the rotatable body may translate relative to the body to define the dose delivery end position of the plunger rod.

[0039] In any of these embodiments, the translation of the rotatable body may provide a first resolution of dose setting, and the rotation of the rotatable body defines a second resolution of dose setting.

[0040] In any of these embodiments, the plunger rod may be rotationally fixed.

[0041] In any of these embodiments, the rotatable body may be laterally offset relative to the plunger rod.

[0042] In any of these embodiments, the axis of rotation of the rotatable body may intersect the plunger rod.

[0043] In any of these embodiments, the rotatable body may include a second stop.

[0044] In any of these embodiments, the assembly may include a locking mechanism to rotationally constrain the dose setting dial in the end-dose delivery position of the plunger rod.

[0045] According to various embodiments, the syringe includes any of the plunger rod assemblies described above.

[0046] In any of these embodiments, the syringe can be a pre-filled syringe.

[0047] In any of these embodiments, the syringe may be a disposable syringe used to inject only one dose.

[0048] In any of these embodiments, the syringe may include a retractable needle cover that locks in the extended position at the end of dose delivery.

[0049] According to various embodiments, a method of setting and delivering a dose using a prefilled syringe includes: applying a first rotational input to a dose setter of the syringe to adjust the relative axial position between at least a portion of the dose setter and a plunger rod of the syringe to set a first dose increment; applying a second rotational input to the dose setter of the syringe to adjust the rotational position of at least a portion of the dose setter to set a second dose increment, wherein the second dose increment is greater than the first dose increment; and axially advancing the plunger rod to deliver a dose from a dose-independent dose starting position.

[0050] In any of these embodiments, the first rotational input may be applied to a dial that is rotatable relative to at least a portion of the dose setter.

[0051] In any of these embodiments, the second rotational input may be applied to a second dial rotatably coupled to at least a portion of the dose setter.

[0052] In any of these embodiments, at least a portion of the dose setter is axially translatable relative to the second dial.

[0053] In any of these embodiments, at least a portion of the dose setter is axially translatable relative to the first dial.

[0054] In any of these embodiments, the first and second rotational inputs may be applied to a dial of at least a portion of the dose setter.

[0055] In any of these embodiments, applying the first rotational input may axially advance the plunger rod relative to the syringe barrel.

[0056] In any of these embodiments, applying the first rotational input may axially advance at least a portion of the dose setter relative to the syringe barrel.

[0057] In any of these embodiments, at least a portion of the dose setter may include at least one stop, the plunger rod may include at least one protrusion, and adjusting the rotational position of at least a portion of the dose setter may include aligning the at least one stop with the at least one protrusion.

[0058] In any of these embodiments, the second rotational input may be applied after the first rotational input is completed.

[0059] In any of these embodiments, the method may further include constraining the dose setter after delivering the dose.

[0060] According to various embodiments, a method of setting and delivering a dose using a prefilled syringe includes adjusting a relative axial position between at least a portion of a dose setter of a syringe and a plunger rod of the syringe; rotating at least a portion of the dose setter to align at least one stop of at least a portion of the dose setter with at least one protrusion of the plunger rod; and axially translating the plunger rod to deliver the dose until at least one protrusion of the plunger rod engages at least one stop of at least a portion of the dose setter.

[0061] The method of claim 50, wherein adjusting the relative axial position between at least a portion of the dose setter and the plunger rod comprises adjusting the axial position of at least a portion of the dose setter relative to a syringe barrel.

[0062] In any of these embodiments, adjusting the relative axial position between at least a portion of the dose setter and the plunger rod may include adjusting the axial position of the plunger rod relative to the syringe barrel.

[0063] In any of these embodiments, adjusting the relative axial position between at least a portion of the dose setter and the plunger rod may include a user applying a rotational input to the dose setter.

[0064] In any of these embodiments, a rotational input may be applied to a dial of the dose setter, which rotates relative to at least a portion of the dose setter and may engage at least a portion of the dose setter such that at least a portion of the dose setter is axially translated by rotation of the dial.

[0065] In any of these embodiments, the rotational input may be applied to a dial that is translationally fixed relative to at least a portion of the dose setter.

[0066] In any of these embodiments, rotating at least a portion of the dose setter can include a user-applied rotational input.

[0067] In any of these embodiments, the plunger rod may remain translationally fixed while at least a portion of the dose setter is rotated.

[0068] In any of these embodiments, at least a portion of the dose setter may remain translationally fixed while at least a portion of the dose setter is rotated.

[0069] In any of these embodiments, the method may further include axially restraining the plunger rod at the end of dose delivery.

[0070] According to various embodiments, a method of delivering a dose using a prefilled syringe includes setting a dose of the syringe by setting an end of travel of a plunger rod of the syringe; axially translating the plunger rod of the syringe to deliver the dose from a dose-independent starting position; and displaying a dose delivery completion indication at the end of travel of the plunger rod.

[0071] In any of these embodiments, the method may further include generating an audible indication of dose delivery completion at the end of travel of the plunger rod.

[0072] In any of these embodiments, the method may further include locking a dose setter of the syringe device at the end of travel of the plunger rod.

[0073] In any of these embodiments, the method may further include withdrawing the syringe from the injection site and locking the needle shield in place after dose delivery is complete.

[0074] In any of these embodiments, after dose delivery is complete, a portion of the dose corresponding to the difference between the total dose and the delivered dose may remain in the syringe.

[0075] It should be understood that any variations, aspects, features and options described with regard to apparatus and components are also applicable to methods, and vice versa. It will also be clear that any one or more of the above variations, aspects, features and options can be combined.

[0076] Specifically, the present invention includes but is not limited to the following:

[0077] 1. A plunger rod assembly for a syringe, comprising:

[0078] main body;

[0079] a plunger rod at least partially received in the body and comprising a set of one or more protrusions; and

[0080] A dose setter operably coupled to the plunger rod and comprising a rotatable body comprising a set of one or more stops for engaging the set of one or more projections of the plunger rod at least in accordance with a rotational position of the set of one or more stops relative to the set of one or more projections, wherein a first rotational adjustment device associated with the dose setter is configured to set a first dose increment by adjusting a relative axial position between the rotatable body and the plunger rod, and a second rotational adjustment device associated with the dose setting assembly is configured to set a second dose increment greater than the first dose increment by adjusting a relative rotational alignment between the set of one or more stops and the set of one or more projections.

[0081] 2. The plunger rod assembly of claim 1 , wherein the first rotational adjustment device comprises a rotatable dial engaging the rotatable body and being rotatable relative to the rotatable body to axially translate the rotatable body relative to the main body.

[0082] 3. The plunger rod assembly of claim 2, wherein the rotatable dial comprises threads that engage threads of the rotatable body.

[0083] 4. The plunger rod assembly according to any one of items 1 to 3, wherein the second rotation adjustment device comprises a dial for rotating the rotatable body.

[0084] 5. The plunger rod assembly of clause 4, wherein the rotatable body is capable of translating relative to the dial.

[0085] 6. The plunger rod assembly of clause 4, wherein the rotatable body and the dial are fixed relative to each other.

[0086] 7. The plunger rod assembly according to any one of items 1 to 6, wherein the first rotation adjustment device adjusts the axial position of the rotatable body relative to the main body.

[0087] 8. The plunger rod assembly according to any one of items 1 to 7, wherein the first rotation adjustment device adjusts the axial position of the plunger rod relative to the body.

[0088] 9. The plunger rod assembly according to any one of items 1 to 8, wherein the plunger rod is rotationally fixed.

[0089] 10. The plunger rod assembly of any one of clauses 1 to 9, wherein the rotatable body is laterally offset relative to the plunger rod.

[0090] 11. The plunger rod assembly according to any one of items 1 to 10, wherein the rotation axis of the rotatable body intersects the plunger rod.

[0091] 12. The plunger rod assembly of any one of items 1-11, wherein the set of one or more protrusions comprises a single protrusion and the set of one or more stops comprises a plurality of stops.

[0092] 13. The plunger rod assembly of any one of items 1 to 12, wherein the set of one or more protrusions comprises a plurality of protrusions and the set of one or more stops comprises a single stop.

[0093] 14. A plunger rod assembly according to any one of items 1-13, wherein the first rotation adjustment device includes a narrow groove in the rotatable body for receiving a portion of the plunger rod, and the narrow groove includes an inclined surface, which axially pushes the portion of the plunger rod received in the narrow groove when the rotatable body rotates.

[0094] 15. The plunger rod assembly of clause 14, wherein the set of one or more protrusions comprises a single protrusion, and the portion of the plunger rod is the single protrusion.

[0095] 16. A plunger rod assembly according to item 14 or item 15, wherein the portion of the plunger rod can be disengaged from one circumferential end of the narrow slot so that continued rotation of the rotatable body does not cause further axial translation of the plunger rod relative to the rotatable body.

[0096] 17. A plunger rod assembly comprising:

[0097] main body;

[0098] a plunger rod at least partially received in the body and comprising one or more protrusions; and

[0099] A dose setting device comprising:

[0100] a rotatable body comprising one or more first stops aligned with the one or more protrusions to define an end-of-dose delivery position of the plunger rod, wherein different alignments of the one or more first stops with the one or more first protrusions define different dose settings, and

[0101] A second stop engages one or more protrusions of the plunger rod to define a dose delivery start position of the plunger rod, wherein the dose delivery start position of the plunger rod is the same for the different dose settings.

[0102] 18. A plunger rod assembly according to claim 17, wherein the one or more protrusions of the plunger rod include a first protrusion, and wherein the engagement between the first protrusion and the second stop member defines a dose delivery start position, and the engagement between the first protrusion and the one or more first stops defines the dose delivery end position.

[0103] 19. A plunger rod assembly according to claim 17 or claim 18, wherein the one or more protrusions of the plunger rod include a first protrusion and a second protrusion, and wherein the engagement between the first protrusion and the second stop member defines the dose delivery start position, and the engagement between the second protrusion and the one or more first stop members defines the dose delivery end position.

[0104] 20. The plunger rod assembly of any one of clauses 17-19, wherein the second stop comprises a slot that receives a first protrusion of the one or more protrusions.

[0105] 21. The plunger rod assembly according to item 20, wherein the narrow slot includes an inclined surface, which pushes the first protrusion received in the narrow slot when the rotatable body rotates in the rotation direction.

[0106] 22. The plunger rod assembly according to item 21, wherein the first protrusion disengages from the narrow slot when the rotatable body continues to rotate in the rotational direction.

[0107] 23. The plunger rod assembly of any one of clauses 17 to 22, wherein the dose setter comprises a rotatable dial engaging the rotatable body and being rotatable relative to the rotatable body to axially translate the rotatable body relative to the main body.

[0108] 24. The plunger rod assembly of clause 23, wherein the rotatable dial comprises threads which engage threads of the rotatable body.

[0109] 25. The plunger rod assembly of any one of clauses 17 to 24, wherein the dose setter comprises a dial for rotating the rotatable body.

[0110] 26. The plunger rod assembly of clause 25, wherein the rotatable body is capable of translating relative to the dial.

[0111] 27. The plunger rod assembly of clause 25, wherein the rotatable body and the dial are fixed relative to each other.

[0112] 28. A plunger rod assembly according to any one of clauses 17 to 27, wherein the rotatable body is translatable relative to the main body to define an end-dose delivery position of the plunger rod.

[0113] 29. The plunger rod assembly of clause 28, wherein translation of the rotatable body provides a first resolution of dose setting and rotation of the rotatable body defines a second resolution of dose setting.

[0114] 30. The plunger rod assembly of any one of clauses 17 to 29, wherein the plunger rod is rotationally fixed.

[0115] 31. The plunger rod assembly of any one of items 17-30, wherein the rotatable body is laterally offset relative to the plunger rod.

[0116] 32. The plunger rod assembly according to any one of items 17 to 31, wherein the rotation axis of the rotatable body intersects the plunger rod.

[0117] 33. The plunger rod assembly of any one of items 17-32, wherein the rotatable body comprises the second stop.

[0118] 34. A plunger rod assembly according to any of clauses 17 to 33, comprising a locking mechanism for rotationally restraining the dose setting dial in the end-dose delivery position of the plunger rod.

[0119] 35. A syringe comprising a plunger rod assembly according to any one of items 1-34.

[0120] 36. A syringe according to claim 35, wherein the syringe is a pre-filled syringe.

[0121] 37. A syringe according to claim 36, wherein the syringe is a disposable syringe used only for injecting one dose.

[0122] 38. The syringe of claim 35 or claim 36, further comprising a retractable needle cover that locks in the extended position at the end of dose delivery.

[0123] 39. A method of setting and delivering a dose using a prefilled syringe, comprising:

[0124] applying a first rotational input to a dose setter of the syringe to adjust a relative axial position between at least a portion of the dose setter and a plunger rod of the syringe to set a first dose increment;

[0125] applying a second rotational input to the dose setter of the syringe to adjust the rotational position of the at least a portion of the dose setter to set a second dose increment, wherein the second dose increment is greater than the first dose increment; and

[0126] The plunger rod is axially advanced to deliver the dose from a dose-independent dose start position.

[0127] 40. A method according to clause 39, wherein the first rotational input is applied to a dial which is rotatable relative to the at least part of the dose setter.

[0128] 41. A method according to clause 40, wherein the second rotational input is applied to a second dial, the second dial being rotationally coupled to the at least part of the dose setter.

[0129] 42. A method according to clause 41, wherein said at least part of said dose setter is axially translatable relative to said second dial.

[0130] 43. A method according to clause 42, wherein said at least part of said dose setter is axially translatable relative to said first dial.

[0131] 44. A method according to any one of clauses 39 to 43, wherein the first and second rotational inputs are applied to a dial of the at least a portion of the dose setter.

[0132] 45. A method according to any one of items 39-44, wherein applying the first rotational input will axially advance the plunger rod relative to the barrel of the syringe.

[0133] 46. ​​A method according to any one of clauses 39 to 45, wherein applying the first rotational input advances the at least a portion of the dose setter axially relative to the barrel of the syringe.

[0134] 47. A method according to any one of items 39-46, wherein at least a portion of the dose setter includes at least one stop member, the plunger rod includes at least one protrusion, and adjusting the rotational position of at least a portion of the dose setter includes aligning the at least one stop member with the at least one protrusion.

[0135] 48. A method according to any of items 39-47, wherein the second rotational input is applied after the first rotational input is completed.

[0136] 49. A method according to any one of clauses 39-48, further comprising constraining the dose setter after delivering the dose.

[0137] 50. A method of setting and delivering a dose using a prefilled syringe, comprising:

[0138] adjusting the relative axial position between at least a portion of a dose setter of the syringe and a plunger rod of the syringe;

[0139] rotating at least a portion of the dose setter to align at least one stop of the at least a portion of the dose setter with at least one protrusion of the plunger rod; and

[0140] The plunger rod is axially translated to deliver the dose until the at least one protrusion of the plunger rod engages the at least one stop of at least a portion of the dose setter.

[0141] 51. A method according to clause 50, wherein adjusting the relative axial position between the at least part of the dose setter and the plunger rod comprises adjusting the axial position of the at least part of the dose setter relative to the barrel of the syringe.

[0142] 52. A method according to clause 50 or clause 51, wherein adjusting the relative axial position between the at least part of the dose setter and the plunger rod comprises adjusting the axial position of the plunger rod relative to the barrel of the syringe.

[0143] 53. A method according to any one of clauses 50 to 52, wherein adjusting the relative axial position between at least a portion of the dose setter and the plunger rod comprises a rotational input applied to the dose setter by a user.

[0144] 54. A method according to claim 53, wherein the rotational input is applied to a dial of the dose setter, the dial rotates relative to the at least part of the dose setter and engages the at least part of the dose setter such that the at least part of the dose setter is axially translated via the rotation of the dial.

[0145] 55. A method according to clause 53, wherein the rotational input is applied to a dial that is translationally fixed relative to the at least part of the dose setter.

[0146] 56. A method according to any of clauses 50-55, wherein rotating said at least a portion of said dose setter comprises a user applied rotational input.

[0147] 57. A method according to any one of clauses 50 to 56, wherein the plunger rod remains translationally fixed while the at least part of the dose setter is rotated.

[0148] 58. A method according to any one of clauses 50 to 57, wherein said at least part of said dose setter remains translationally fixed while said at least part of said dose setter is rotated.

[0149] 59. The method according to any one of items 50-58, further comprising axially constraining the plunger rod at the end of dose delivery.

[0150] 60. A method of delivering a dose using a prefilled syringe, comprising:

[0151] Setting the dose of the syringe by setting the end of travel of the plunger rod of the syringe;

[0152] axially translating the plunger rod of the syringe to deliver the dose from a dose-independent starting position; and

[0153] A dose delivery complete indication is displayed at the end of the plunger rod's travel.

[0154] 61. A method according to item 60, further comprising generating an audible indication of dose delivery completion at the end of travel of the plunger rod.

[0155] 62. A method according to item 60 or item 61, further comprising locking a dose setter of the syringe device at the end of travel of the plunger rod.

[0156] 63. A method according to any one of items 60-62, further comprising withdrawing the syringe from the injection site and locking the needle shield in place after dose delivery is completed.

[0157] 64. A method according to any one of items 60-63, wherein after dose delivery is completed, a portion of the dose corresponding to the difference between the total dose and the delivered dose remains in the syringe. BRIEF DESCRIPTION OF THE DRAWINGS

[0158] The present invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0159] Figure 1 A conventional syringe is shown, which is a syringe with the left end being the patient end and the right end being the non-patient end;

[0160] Figure 2 A syringe according to various embodiments is shown which is a variable dose device;

[0161] Figure 3 According to various implementation schemes Figure 2 Exploded views of various aspects of the syringe barrel;

[0162] Figure 4a and Figure 4b Various aspects of a dose stop according to various embodiments are shown;

[0163] Figure 5 and Figure 6 is an example of a dose setting dial according to various embodiments, Figure 5 The left figure of is the top view, front view and bottom view from top to bottom; Figure 6 For coarse dose setting dial, Figure 6 The left side of the figure shows, from top to bottom, a top view, a front view, and a bottom view of the coarse dose setting dial;

[0164] Figure 7 shows a plunger rod according to various embodiments;

[0165] Figure 8 shows a housing of a plunger rod assembly according to various embodiments;

[0166] Fig. 9 Various features for retaining a plunger rod assembly on a syringe body are shown, particularly showing syringe retention, according to various embodiments;

[0167] Fig.10 A dose setter according to various embodiments is shown, which is a dose setting mechanism;

[0168] Fig.11 a. Fig.11 b and Fig.11 c shows various dosage settings according to various embodiments;

[0169] Fig.11 a' shows the position of the plunger rod relative to the groove according to various embodiments;

[0170] Fig.12 1. The process for setting and delivering a dose according to various embodiments is shown, specifically a 0.440 mL dose, with left panel AC being a front view and right panel AC being a side view;

[0171] Fig.13 illustrates locking of a dose setting dial at the end of dose delivery according to various embodiments;

[0172] Fig.14 illustrates an exemplary plunger stopping force according to various embodiments, specifically a plunger stopper being loose;

[0173] Fig.15 A syringe according to various embodiments, specifically a second embodiment variable dose syringe, components are shown;

[0174] Fig.16The plunger rod according to various embodiments is shown, and the right figure is a left side view, a front view, a right side view and a rear view of the plunger rod from left to right, and the upper end of each view is the patient end and the lower end is the non-patient end;

[0175] Fig.17 shows a housing according to various embodiments;

[0176] Fig.18 Shows a latch according to various embodiments, with the second, third, and fourth figures from left to right showing a cutaway plane, a cross-sectional view, and a cutaway plane, respectively;

[0177] Fig.19 and Fig. 20 shows aspects of a dose setter according to various embodiments, Fig.19 The dose setting dial and the dose stop are shown, the second figure from left to right is a rear view, and the third figure from top to bottom is a bottom view, a front view and a top view; Fig. 20 is a cross-sectional view of a dose setting dial and a dose stop, wherein the leftmost arrow indicates the cut plane;

[0178] Fig.21 and Fig. 22 shows a cover according to various embodiments, Fig.21 The three pictures below are the front view, side view and back view of the cover from left to right. Fig. 22 The cover is shown attached to the housing;

[0179] Fig.23 A process for setting and delivering a dose according to various embodiments is shown, specifically the case of setting and delivering a 0.2 mL dose volume;

[0180] Fig.24 shows a process for setting and delivering a dose according to various embodiments, specifically setting and delivering a 2.0 mL dose volume;

[0181] Fig.25 shows a fine resolution plunger rod stroke, in particular a high resolution plunger rod stroke, according to various embodiments, the upper panel showing dose setting, the lower panel showing start, both panels on the left being front views, both panels on the right being rear views;

[0182] Fig.26The plunger rod strokes of two different dose settings according to various embodiments are shown, specifically the rough resolution of dose administration - 0.2 mL, 2.0 mL volume (cross-sectional view) and plunger rod locking, the second and third images from left to right are the dose start and dose end of 0.2 mL volume, respectively, and the fourth and fifth images from left to right are the dose start and dose end of 2.0 mL volume, respectively;

[0183] Fig. 27 and Fig.28 shows a syringe cap according to various embodiments, Fig. 27 A second embodiment is shown with a syringe cover and needle stick prevention features, Fig.28 The situation of needle stick protection is shown;

[0184] Fig.29 A syringe according to various embodiments is shown, which is a third embodiment;

[0185] Fig.30 The plunger rod according to various embodiments is shown, which is the plunger rod of Embodiment 3. The second, third, fourth and fifth figures from left to right are respectively the left side view, the front view, the right side view and the back view of the plunger rod, and the upper end of each view is the patient end, and the lower end is the non-patient end;

[0186] Fig.31 shows alternative plunger rod designs according to various embodiments;

[0187] Fig.32 and Fig.33 shows a dose setter according to various embodiments, Fig.32 The dose setting dial is shown, and the right figure is a top view, a front view and a bottom view of the dose setting dial from top to bottom; Fig.33 Dose setting dial beam operation is shown;

[0188] Fig.34 Shown are covers according to various embodiments, with the second panel being a front view of the cover, the upper panel being a rear view, and the lower panel being a top view from left to right;

[0189] Fig.35 Shows a housing according to various embodiments, the second figure from left to right is a side view of the housing, the third figure from left to right is a bottom view, a front view and a top view from top to bottom;

[0190] Fig.36 An end-of-dose indicator according to various embodiments is shown, which is an end-of-dose barrel, and the right figure is a top view, a front view, and a bottom view of the end-of-dose barrel from top to bottom;

[0191] Fig.37A disk for preventing the plunger rod from rotating according to various embodiments is shown, and the right figure is a top view, a front view, and a bottom view of the disk from top to bottom;

[0192] Fig.38 Window covers according to various embodiments are shown, and the second and third figures from left to right are a side view and a front view of the window cover, respectively;

[0193] Fig.39 A syringe according to various embodiments is shown as an assembled embodiment without a cap;

[0194] Figure 40-Figure 42 Various dose settings and dose deliveries according to various embodiments are shown, Fig.40 The dose setting is shown; Fig.41 The relative positions of the dose setting dial and the plunger rod during dose setting are shown; Fig.42 Setting and delivering 0.2 mL and 2.0 mL doses are shown; and

[0195] Fig.43 A syringe with a needle shield according to various embodiments is shown, which is an embodiment with a needle shield. DETAILED DESCRIPTION

[0196] According to various embodiments, the devices and methods described herein relate to controlled dose delivery, such as using a syringe or cartridge. In order to provide appropriate resolution when setting a low volume (less than 100 microliters) or a higher volume (>100 microliters to milliliters) dose, various embodiments include separate features for higher volume and low volume dose settings - hereinafter generally referred to as coarse and fine dose settings, respectively. The combination of these two settings provides a wide range of dose setting options from low microliters to milliliters in a compact configuration that is practical to use. Separating the coarse and fine injection dose volume settings avoids the redundancy of having microliter level resolution for milliliter dose volumes, but provides the necessary resolution for injection microliter volumes.

[0197] According to various embodiments, the controlled dose delivery device may include a syringe, a plunger stop, a plunger rod, a dose stop, one or more dose setting dials, which may include a fine dose setting dial and a coarse dose setting dial or a single dial that can control fine and coarse dose settings. According to various embodiments, the syringe may be a pre-filled syringe with an elastic plunger stop translated by a plunger rod. The plunger rod moves axially to distribute the injectable drug filled in the syringe. The amount of the plunger rod axial stroke defines the volume of the injected dose. The plunger rod translates axially until the design feature on the plunger rod abuts against the "stop" feature of the dose stop.

[0198] According to various embodiments, the dose stop may have one or more radially arranged "stop" features, and the plunger rod may have one or more radially arranged protrusions, and the corresponding alignment between the stop features and the protrusions corresponds to the dose setting. The "stop" features and / or the protrusions may be arranged at different longitudinal / axial positions. For example, the dose stop may include multiple stop features at different axial and circumferential positions, and rotation of the dose stop may align a specific stop feature with the protrusion of the plunger rod to set a dose corresponding to the specific stop feature. Aligning different stop features with the protrusions will set different doses.

[0199] According to various embodiments, the fine dose setting dial may engage with the dose stop such that rotation of the fine dose setting dial causes axial translation of the dose stop, which axially translates one or more stop features of the dose stop to provide fine adjustment of the dose setting. The dose stop and / or the dial may have threads, and the thread angle and pitch may define the resolution of the fine dose adjustment. The selectivity of the alignment of a particular stop feature with a particular protrusion may provide coarse dose setting adjustability, while the axial / longitudinal position of the dose stop may provide fine dose setting adjustability. Thus, the user may select the amount of the dose by a combination of the fine dose setting dial and the coarse dose setting dial.

[0200] According to various embodiments, the higher resolution of the plunger rod stroke is reserved for a portion of the entire plunger rod stroke, for example, for micro-advancing the plunger rod to prime the syringe in a controlled manner and / or to help overcome the static friction of the plunger stop. According to various embodiments, a single dose setting dial combines features of high resolution and coarse resolution for axial translation of the plunger rod. As described above, one or more stop features corresponding to the amount of various user-selectable doses can be incorporated into the dose setting dial or the plunger rod. The plunger rod may include one or more radially extending protrusions, one or more of which may be used for dual purposes, namely interacting with one or more stop features on the dose setting dial and enabling the plunger rod to be micro-advanced (high resolution stroke) by a partial rotation of the dose setting dial. The plunger rod may include features that provide audible and visual end-of-dose indications, as well as tactile end-of-dose indications generated by the protrusions on the plunger rod abutting against the stop features on the dose setting dial at the end of the dose. Visual and audible end-of-dose indications are important for providing the user with confirmation that the injection process is completed in the system, wherein the end-of-dose position of the plunger rod varies according to the dose selected by the user.

[0201] According to various embodiments, according to various embodiments, stop features corresponding to the amount of various user-selectable doses are incorporated into the plunger rod. Depending on the selected dose volume, one of these stop features can translate until it reaches the stop feature of the dose stop to define the end of delivery of the intended dose (dose end). According to some embodiments, simultaneous with the end of the dose is an audible and / or visual dose end indication to the user. The visual dose end indication may include a dose end barrel that translates axially toward the injection end stroke, wherein the colored features of the marking are visible to the user when approaching the injection end stroke.

[0202] According to various embodiments, the syringe is a pre-filled disposable syringe for injecting only one dose. According to various embodiments, in the absence of administration of the maximum possible volume of the drug in the syringe, the undelivered drug remaining in the syringe is considered a biohazard. In order to minimize the possibility of misusing such unused drug by reusing the device, the plunger rod and dose setting dial can be locked in place.

[0203] According to various embodiments, the drug delivery device may include one or more needle safety features for embodiments in which the needle is pre-attached (fixed) to the syringe barrel in any of the above-described device embodiments. According to various embodiments, the needle safety device is actuated independently of the dosing mechanism. According to other embodiments, the needle safety device is actuated by the injection stroke, such as near the end of the dose. The actuation of the needle safety device can disable the injection device. Therefore, according to various embodiments, the actuation of the needle safety device by completing the injection can disable the injection device and ensure that the needle safety device is only actuated when the dose selected by the user is delivered.

[0204] According to various embodiments, the prefillable syringe may have a flange, such as circular or having diametrically opposed flat surfaces, and one or more features on an element incorporated into the syringe retaining component of the device minimize rotation of the syringe, regardless of the design of the syringe flange.

[0205] In the following description of the present disclosure and embodiments, reference is made to the accompanying drawings, in which specific embodiments that can be implemented are shown by way of illustration. It should be understood that other embodiments and examples can be implemented, and changes can be made, without departing from the scope of the present disclosure.

[0206] In addition, it should also 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 "includes", "including", "comprises", and / or "comprising", when used herein, 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 groups thereof.

[0207] Figure 1 A conventional syringe-based delivery system is shown, which includes a cylindrical barrel 1, the inner surface of which can be lubricated to enable an elastomeric plunger stopper 2 to translate along the barrel axis by a standard plunger rod 3. The user can select a dose by aligning the tip of the stopper with a dose volume marker 4 printed on the outer surface of the barrel 1. This will be the dose start position. Then, the user inserts a delivery catheter (e.g., a needle, catheter, etc. connected to or pre-attached to the syringe) into the injection site and axially depresses the plunger rod 3 until the plunger stopper bottoms out. The above dose marker 4 provides the same resolution for dose setting regardless of whether the user selects a dose at the low or high end of the volume range. In Figure 1 the example shown, if the expected dose is less than 0.1 ml, a higher resolution is desired to ensure accurate and precise delivery. Conversely, in the example shown, the resolution required to accurately and precisely deliver a 0.9 ml dose is sufficient. In addition, if a pre-filled syringe (where 1 ml of drug is filled by the drug manufacturer) is to be used to administer a low volume (e.g., Figure 1 0.1 ml in the current example), the user will have to eject 0.9 ml of the drug before administering the injection. In the case of potent drugs such as chemotherapeutic agents, oncolytic viruses, gene therapies, etc., exposing the wasted drug to the user can be harmful to the user, caregiver, and family members. This situation is unique to all non-pen syringe-based drug delivery device solutions in the prior art. If only a portion of the total drug encapsulated in the syringe is to be delivered, it is desirable to administer only the expected dose and retain the remaining dose in the syringe. The used syringe with the undelivered drug can be safely disposed of without unnecessary exposure to the drug.

[0208] According to various embodiments, Figure 2Variable dose syringe 100 is shown in the figure, it is configured to provide the user with control of the dosage setting resolution, so that the user can select the injection volume and prevent unnecessary exposure to excessive medicine. Variable dose syringe embodiment provides the separate fine and rough setting of expected dose volume. The embodiment shown is intended to deliver up to 1 milliliter with setting dose resolution 0.1 milliliter or 0.01 milliliter (that is, 10 microliters), depending on the expected volume to be injected. Therefore, 100 dosage volume levels (0.01 milliliter minimum dose to 1 milliliter maximum dose, increment is 0.01 milliliter) can be realized by the variable dose syringe shown in this article. Figure 3 Components of a variable dose syringe 100 according to various embodiments are shown. For example, a standard prefillable syringe 9 with a maximum fill volume of 1 ml can be used, with a needle pre-attached (fixed) therein, but it should be understood that the apparatus, methods and principles described herein can be used with any syringe size and any syringe configuration.

[0209] The variable dose syringe 100 includes a plunger rod assembly, which can be attached to the proximal end of the syringe 9, for example, by a clip 14 and an X-ring 15. The plunger rod assembly can include a housing 16 (also referred to herein as a body), a plunger rod 10, a dose setter including a rotatable body 13 (hereinafter also referred to as a "dose stop") and one or more dials (diales 11 and 12 are shown). The syringe 9 can be filled with an injectable drug 8 and include an elastic plunger stop 7. According to various embodiments, fine and coarse dose volume settings are facilitated by a fine dose setting dial 11 and a coarse dose setting dial 12, respectively. The device includes a dose stop 13. The above components are supported or contained in the housing 16. The prefillable syringe 9 is retained on the housing 16 by a clip 14 and an elastic X-ring 15.

[0210] Pre-filled syringes with pre-attached (or fixed) needles are typically provided to the user in a ready-to-inject form. Similarly, according to various embodiments, the variable dose syringe 100 may have a pre-filled syringe 9 in which the axial position of the plunger rod 10 is in a dose start position provided to the end user. The dose end position may be defined by a dose stop 13. Embodiments of the dose stop 13 are Figure 4a As shown in Figure 4aAs shown, the end of dose is facilitated by a stop surface 18 on the dose stop 13. Each stop surface 18 is arranged circumferentially and each corresponds to a coarse dose volume that can be set. The axial position of each stop surface 18 is defined by the dose volume amount on the coarse dose setting dial 12. The dose stop 13 comprises four spline segments 19, each having the same length, arranged at the same axial position on the dose stop 13 and arranged at 90 degrees relative to each other. These spline segments 19 interact with the coarse dose setting dial 12. The dose stop 13 also comprises a thread 20, which interacts with the fine dose setting dial 11. In Figure 4b 1 shows a partial expansion of the dose stop surfaces of the cylindrical dose stop 13, the stop surface 18a corresponds to the lowest volume on the coarse dose setting dial 12, and the stop surface 18j corresponds to the highest volume on the coarse dose setting dial 12. The end-of-dose position of the plunger rod 10 is determined by one of the stop surfaces 18, the axial position of which is a combination of the coarse dose setting and the axial advancement of the dose stop 13 mediated by the rotation of the fine dose setting dial 11. The resolution of the fine dose setting is determined by the angle of the internal thread 20.

[0211] Figure 5 An example of a fine dose setting dial 11 is shown, which includes an outer thread 21 to match the pitch and thread angle of the inner thread 20. Indicia 22 corresponding to fine dose levels providing finer resolution of dose setting are printed on the cylindrical surface of the fine dose setting dial 11. Radial grooves 23f are located on the bottom surface. Each groove 23f is spaced apart at an angle defined by the amount of rotation of the fine dose setting dial 11 so that the axial translation of the dose stop 13 corresponds to the dose volume resolution provided by the fine dose setting dial 11. The grooves 23f help to fix the rotational position of the fine dose setting dial 11. The dose stop 13 is arranged in the cavity 24. The longitudinal grooves 27f on the cylindrical surface of the fine dose setting dial 11 are separated by the same angle as 23f; these longitudinal grooves play a role in locking the fine dose setting dial at the end of the injection. The friction between the mating threads 20 and 21 axially constrains the dose stop 13.

[0212] Figure 6An example of a coarse dose setting dial 12 is shown in FIG, which includes an axial keyway 25 which aligns with and accommodates a spline segment 19 on a dose stop 13. A radial groove 23c is located on the top surface. The groove 23c helps to fix the rotational position of the coarse dose setting dial 12. Each groove 23f is spaced at the same angle as the angle between the stop surfaces 18, and the number of grooves 23c is one more than the number of stop surfaces 18. The longitudinal grooves 27c on the cylindrical surface of the coarse dose setting dial 12 are spaced at the same angle as 23c; these longitudinal grooves play a role in locking the fine dose setting dial at the end of an injection. The dose stop 13 is disposed in a cavity 28. Indicia 26 corresponding to a coarse dose level providing a coarse resolution of the dose setting are printed on the cylindrical surface of the fine dose setting dial 12.

[0213] According to various embodiments, the plunger rod 10 is characterized by Figure 7 . The locking blade 29 and the low dose locking blade 30 are longitudinally disposed but axially separated from each other and from the dose stop mark 31. The user performs the injection by pushing the finger seat 32, which helps to axially translate the plunger 10 until the dose stop mark travel is interrupted by the stop surface 18 on the dose stop 11; the stop surface and its axial distance from the start of the injection are defined by the fine dose setting dial 11 and the coarse dose setting dial 12. The distal end 43 of the plunger rod meets the side of the plunger stop 7 opposite to the drug contact side. In some applications, the distal end 43 may be adapted to cooperate with the plunger stop 7.

[0214] Figure 8 38. The features of the housing 16 are shown in FIG. The axial cavities 33 and 34 contain the dose stop 13 and the plunger rod 10, respectively. The fine dose setting dial 11 is placed in the side slot 35, while the coarse dose setting dial 12 is placed in the side slot 36. Along the axis of the device, the side slot 35 is bounded by a hollow circular beam with a marking tip 17f. The tip of 17f helps to record the dose setting position of the fine dose setting dial 11 when located in the groove of the radial groove 23f. Along the axis of the device, the side slot 36 is also bounded by a hollow circular beam with a marking tip 17c. The tip of 17c helps to record the dose setting position of the coarse dose setting dial 12 when located in the groove of the radial groove 23c. The deflection of the two circular beams is sufficient to rotate the fine and coarse dose setting dials. The fine and coarse dose setting dials are axially constrained by the housing 16 and radially constrained by the dose stop 13. The syringe is attached to the housing 16 by placing it in the cavity 38.

[0215] The clip 14 and x-ring 15 can be used to attach the pre-filled syringe 9 to the housing 16 (see Fig. 9). The x-ring is placed in cavity 38. To attach the syringe 9 to the housing 16, the syringe flange 41 is placed between the clip 14 and the housing 16 when inserted into the cavity 38, so that the tabs 39 on the clip 14 are aligned with the axial keyways on the housing 16 until the inclined slot 37 is reached. Using a torque wrench with an adapter to engage the slot 39, the clip is turned along the ramp defined by the slot 37 until it is tight. The pre-filled syringe is now secured to the housing 16, and therefore to the device.

[0216] The mating features 19 and 25 can be used to enable the coarse dose setting dial 12 to be rotationally keyed to the dose stop 13, and to enable the coarse dose setting dial 12 to slide axially relative to the dose stop 13. The stop surface 18 on the dose stop 13 defines the end-dose position of the plunger rod dose stop mark 31. Rotation of the fine dose setting dial 11 causes an axial translation of the dose stop 13. The end-dose position is defined by the axial position of the stop surface 18, which in turn depends on the combination of the volume selected on the coarse dose setting dial 12 and the volume selected on the fine dose setting dial 11. Manipulation of the fine dose setting dial 11 adjusts the axial position of the stop surface 18 corresponding to each setting of the coarse dose setting dial 12. Therefore, the user can selectively adopt a higher resolution dose setting or a coarse resolution dose setting or a combination thereof to effectively set the dose volume to be injected. Compared with variable dose systems such as pen-type injectors in the prior art, another dose setting advantage is that the user does not have to set the target dose volume through all dose levels. For example, to set a 0.2 ml dose, the user only needs to rotate the coarse dose setting dial 12 to set a 0.2 ml dose without having to go through 0.01 ml increments up to 0.2 ml.

[0217] Fig.11 a shows the positions of the coarse dose setting dial 12 and the fine dose setting dial 11 before the user operates to set a dose according to various embodiments. According to various embodiments, the dose starting position of the plunger rod 10 is defined by the abutment between the locking blade 29 of the plunger rod 10 and the proximal end of the dial 11, which prevents the plunger rod 10 from being advanced by the user. The markings 17c and 17f on the circular beam on the housing 16 provide a visual reference for the user to set the dose volume based on the markings 22 and 26 on the fine and coarse setting dials, respectively. Fig.11 The examples of 11a, 11b and 11c of FIG. 1 show dose volumes set to 0.000, 0.460 and 1.000 ml of injection. Corresponding to when the dose volume is 0.000, the locking blade 29 of the plunger rod 10 is not longitudinally aligned with the groove 27f, as shown in 11a'. The dose setting makes the locking blade longitudinally aligned with the groove 27f. The plunger rod 10 is now in the dose start position.

[0218] Fig.12 Various aspects of the internal mechanism for dose setting and end of dose for an exemplary 0.440 ml injection according to various embodiments are shown. The internal mechanism including the fine dose setting dial 11, the coarse dose setting dial 12, the dose stop 13 and the plunger rod 10 corresponding to the device state received by the user is shown in "a". Rotating the fine dose setting dial to align the "40" mark with the mark 17f on the housing 16, and rotating the coarse dose setting dial to align the "0.4" mark with the mark 17c on the housing 16 helps to rotationally align and axially position the stop surface 18 on the dose stop 13; this is shown in "b". "c" shown is after the user depresses the plunger rod 10 causing the plunger rod 10 to translate axially until the end of dose mark 31 abuts the stop surface 18; this also provides tactile feedback to the user that the intended dose has been delivered. The total axial travel described above is the injection stroke 42.

[0219] It may be advantageous to lock the dose setting dial after the injection has been completed; this option is available in Fig.13 For the same 0.440 ml example above, Fig.13 "b" in Figure 4 shows the internal mechanism when the user sets a dose. After the injection stroke 42 is completed, the locking blade 29 is axially translated within the grooves 27c and 27f of the coarse dose setting dial 12 and the fine dose setting dial 11. The presence of the locking blade 29 prevents further rotation of the fine dose setting dial 11 or the coarse dose setting dial. This makes the device unable to be used to deliver any undelivered drug in the syringe 9 after the intended dose is over. Only for low dose volumes, the low dose locking blade 30 functions to lock the coarse dose setting dial.

[0220] In embodiments involving pre-filled syringes or pre-filled cartridges, after aseptic filling of the drug, the syringe (or cartridge) is stopped with an elastic plunger stop. The plunger stop is radially oversized relative to the inner diameter of the syringe (or cartridge) to provide and maintain a sterile barrier. Over time and during storage of the pre-filled drug, the elastic plunger stop will generate an inertia called static friction to the movement, wherein the plunger stop must be loosened before it can translate axially. Fig.14 An exemplary injection force curve illustrating this phenomenon is shown. Static friction has several practical implications. An increase in the amount of axially applied force 5 to overcome static friction can cause the user to lose control of the plunger stop travel (due to momentum). This loss of user control ultimately results in wasted medication. An increase in force 5 can also trigger an occlusion alarm in an automated delivery system such as an infusion pump. In addition, Fig.14, the amount of plunger stop travel corresponding to when static friction begins to take effect is very small relative to the total expected travel of the plunger stop to administer the expected volume of drug. It is desirable to be able to controllably advance the plunger stop to overcome static friction before showing that the drug can be advanced by a predictable force 6.

[0221] In view of the above, in drug delivery applications based on pre-filled syringes (or cartridges), it is desirable to have a higher resolution of the plunger stop stroke to overcome static friction, i.e., to reserve a higher resolution for the plunger stop stroke amount only for overcoming the plunger stop static friction. A coarser resolution can then be provided for other preset dose volume amounts. Presetting dose levels is only possible when the various doses of a given injectable drug 8 are known in advance. Fig.15 A variable dose syringe 43 according to various embodiments is shown, which can overcome plunger stopper static friction and provide fine and coarse resolution. The syringe 43 can be used, for example, to deliver a minimum of 0.2 ml and a maximum of 2.0 ml (i.e., 10 dose volume levels - 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0 ml) in increments of 0.2 ml. It should be understood that these delivery amounts and increments are merely exemplary, and the syringe 43 can be configured to deliver any suitable amount and increment.

[0222] The syringe 43 includes a plunger rod assembly that can be assembled to the syringe 9. The plunger rod assembly can include a plunger rod 44, a housing 45, a cap 46, and a dose setting device 47 (also referred to herein as a dose setting dial 47). The illustrated embodiment includes a pre-filled syringe 9 containing an injectable drug 8 stopped by a plunger stop 7. Similar to Figure 2 The prefilled syringe 9 is fixed to the housing 45 using a clip 14 and an elastic x-ring.

[0223] According to various embodiments, the plunger rod 44 is Fig.16. The patient end of the plunger rod 44 includes a disc 48 to allow the user to manually advance the plunger rod 44 after setting the dose. The cylindrical patient end 49 abuts the plunger stop 7 when assembled. The end 49 can also be modified to have a thread that interlocks with the axial non-drug contact side of the plunger stop 7. A pull latch 47 can be used to provide control of the axial plunger rod 44 stroke. The plunger rod 44 includes four longitudinal ribs 50, which, together with the features on the housing 45 and the cover 46, help prevent the plunger rod 44 from rotating during device operation. The marking 51 includes a high-resolution drive surface 52 on the non-patient end and a stop surface 53 on the patient end. The plunger rod 44 also includes a beam 54, which helps to provide an audible end-of-dose indication and axially locks the plunger rod 44 once the selected dose is fully delivered (dose end). The plunger rod 44 also includes a flat surface with a dose end mark 55 corresponding to various deliverable dose volumes. The intervals of the dose volume mark correspond to the injection stroke of the respective dose volume.

[0224] According to various embodiments, the housing 45 is Fig.17 . It includes a dose setting latching ratchet 56. A flange portion 57 is provided for the user to grip the device during injection. A cavity 58 radially constrains the plunger rod 44. A side slot 59 is provided to allow the user to access the dose setting dial 47. An axial slot 60 provides alignment for inserting the tab 40 on the clip 14 during insertion of the syringe 9 before attachment. Slot 61 provides an inclined slot for the tab 40 when the clip 14 is rotated to securely attach the syringe 9 to the housing 45. In Fig.18 Detailed description of the latch 56 according to various embodiments is shown in FIG. 5 , which consists of a hemispherical peg 63 and a latch 62. The height of the hemispherical peg is slightly greater than the height of the latch 62. The latch 56 provides tactile and audible feedback to the user during dose setting, and interacts with features on the dose setting dial 47 housed within a concave cylindrical portion 66 of the housing 45. Surfaces 64 and 65 help to axially constrain the dose setting dial 47.

[0225] The dose setting dial 47 according to various embodiments is Fig.19. The dose setting dial 47 comprises a rotatable body having a plurality of dose stops 76 which engage the markings 51 of the plunger rod 44 to stop the axial travel of the plunger rod 44, thereby controlling the end of dose delivery. The portion 67 of the dose setting dial 47 is contained within the portion 66 of the housing 45. The dose markings 68 are printed to enable the user to select the injection volume (dose setting). The portion markings 69 include a “→” marking indicating to the user the initial rotation direction of the dose setting dial 47. Only one of these markings 68 is visible to the user through the cover 46. The surface 69 abuts against the surface 64 of the housing 45, constraining the dose setting dial 47 axially towards the patient end. The surface 70 is constrained by the surface 65 of the housing 45, thereby constraining the dose setting dial 47 in the non-patient end direction. The dose setting dial 47 consists of a plurality of longitudinal splines 71. The markings 51 of the plunger rod 44 are constrained within these splines 71. The longitudinal groove 72 on the portion 67 of the surface of the dose setting dial 47 interacts with the pegs 62 and 63 of the latch 56. Among them, the grooves 72a, 72b and 72c are longer than the other grooves to accommodate the pegs 62 and 63. The rest of the groove 72 accommodates only the peg 63. When not in use, the pegs 62 and 63 are located in the groove 72a. The shape of the groove 72a ensures that the dose setting dial 47 is rotated only in the direction indicated by the "→" part of the mark 68. After rotating the dose setting dial 47 by an angle corresponding to 74°, and when reaching the groove 72b, the dose volume is set to 0.2 ml. The shape of the groove 72b (same as the shape of 72a) prevents the user from returning to "→"; this groove 72 accommodates the pegs 62 and 63. Continuous rotation towards the other hemispherical groove 72 only engages the hemispherical peg 63. The hemispherical shape of the other groove 72 allows bidirectional rotation of the dose setting dial 47, except in the positions corresponding to 0.2 and 2.0 ml. This arrangement prevents transition from 2.0 ml to the "→" position or from 0.2 ml to the "→" position, but at the same time allows the user to flexibly move back and forth between other dose levels before injection. The side slot 73 provides and defines the high resolution of this embodiment. The slot constrains the mark 51 of the plunger rod 44. When the device is not in use, the mark 51 is located at position 75a. The surface 52 of the mark 51 contacts the surface 73a. When the dose setting dial 47 is rotated, the mark 51 axially translates a distance 75 to a position 75b. Once the mark 51 reaches 75b, there is more axial constraint on the stop surface 53 on the plunger rod 44. For any dose volume that can be set in this embodiment, the plunger rod 44 is in the axial dose starting position. In this example, the dose setting at this rotational position of the dose setting dial 47 is 0.2 ml. Distance 75 is a fine resolution of the axial translation of the plunger rod 44, which helps to overcome the static friction of the plunger stop 7 and in some cases also helps to irrigate the delivery catheter, such as an injection needle.The end-of-dose position is defined by surfaces 76 that are axially separated based on an injection stroke corresponding to a dose volume selected by the user by rotating the dose setting dial 47. The surface 76 corresponding to the user-set dose volume is longitudinally aligned with the stop surface 53 on the plunger rod 44. The plunger rod 44 is contained within a cavity 78.

[0226] Fig. 20 A cross-sectional view of features on the dose setting dial 47 is provided. Surface 77 engages the tip of beam 54 of the plunger rod 44. At the end of the dose, the beam 54 strikes surface 77 to provide an audible end-of-dose indication. Surface 79 engages beam 54, thereby axially locking the plunger rod 44 in the non-patient direction at the end of the dose. Thus, at the end of the dose, the plunger rod is axially locked in the patient direction by the engagement of surfaces 53 and 76, and axially locked in the non-patient direction by the interaction of beam 54 and surface 79. The user interface 80 on the dose setting dial 47 for rotating it may include ridges or textures for gripping. Figure 2 Unlike the previous embodiment shown, the fine resolution travel and dose stops are encoded onto the dose setting dial 47 .

[0227] The interaction between surfaces 73a and 52 is similar to Figure 2 The coarse dose setting interaction between surfaces 53 and 76 is similar to Figure 2 Features 18 and 31 of the embodiment described herein.

[0228] According to various embodiments, the device cover 46 is Fig.21 43. It comprises the other half of the flange 57 and the slot 59 for the dose setting dial 47. The surfaces 64 and 65 together with the surfaces inside the housing 45 provide axial constraint to the dose setting dial 47 internally. The slot 81 on the top surface engages to constrain the rib 50 of the plunger rod 44 rotationally. Since the plunger rod 44 is axially locked when the end of the dose is reached, the rotational locking of the plunger rod 44 by the slot 81 prevents the rotation of the dose setting dial 47 because its spline 71 is rotationally keyed with the marking 51 of the plunger rod 44. Therefore, at the end of the dose, in addition to the plunger rod 44 being axially locked, the dose setting dial 47 is rotationally locked, thereby disabling the device and preventing reuse, even if some amount of undelivered drug 8 remains in the syringe 9 contained in the device 43. At the end of the dose, the window 82 provides visibility for the marking 55 corresponding to the injected dose volume. During dose setting, only the marking 68 corresponding to the dose volume setting is visible to the user through the window 83. Upon receiving the device 43, the user sees "→" in the window 83. The pinhole 85 is used during assembly, such as Fig. 22A locating pin 85 that is slightly oversized (radially) relative to the pinhole 85 is used to assemble the cover 46 to the housing 45. The locating pin 85 can also be incorporated as a post and molded into the cover 46 or housing 45 as part of the mold.

[0229] The device for setting and delivering a 0.2 ml dose operates at Fig.23 . The device received by the user is shown as shown in "a". "→" is visible in window 83. The corresponding axial position of the plunger rod 44 is shown as "86". The user rotates the dial 47 in the direction indicated by the "→" mark 68. Once the dose setting dial is rotated by angle 74, the dose volume is now set to "0.2" ml (depicted in "b"). The corresponding axial position 87 of the plunger rod 44 is the dose start position. Once the delivery catheter, such as a needle, is at the injection site, the user uses the disk 48 to depress the plunger rod 44 until the plunger rod 44 cannot translate further; this is the dose end position depicted by 88. In this position, the mark 55 is also visible in the window 82, thereby providing a visual dose end indication to the user. At the end of the dose, the marks 68 and 55 are the same dose volume amount. The position of the patient end 49 of the plunger rod 44 at the dose start 87' and the dose end 88' is also shown. The axial position differences between 88 and 87 and between 88' and 87' are the same and represent the injection stroke of the dose set by the user, in this case 0.2 ml. The distance traveled between position 86 and position 87 of the plunger rod 44 is a fine resolution stroke that helps overcome the static friction of the plunger stop 7. This stroke is Fig.19 The same as shown in 75. In some cases, this fine resolution stroke can also help to priming the delivery catheter to minimize the risk of underdosing.

[0230] Fig.24 Operation of the device for setting and delivering a 2.0 ml dose is shown according to various embodiments. Even when the dose is set to 2.0 ml, the corresponding dose start position 87 is the same as when the 0.2 ml dose is set; this is also true for all other dose volumes in between. The dose end position corresponding to the 2.0 ml dose is indicated by 89, and the corresponding position of the patient end of the plunger rod is 89'. The axial difference between 89 and 87 and 89' and 87' is the injection stroke of the 2.0 ml dose in the syringe 9.

[0231] Fig.25 Also shown is a fine resolution stroke to overcome the static friction (and potential priming) of the plunger stop 7. The front and rear views (housing not shown) show how rotation of the dose setting dial 47 moves the marking 51 from 75a to 75b, resulting in a higher resolution of the axial stroke 75 (e.g. Fig.19 shown).

[0232] Fig.26The cross-sectional view in shows the device operation (dose start and dose end) of delivering exemplary 0.2 ml dose and 2.0 ml dose according to various embodiments. When setting a 0.2 ml dose, the plunger rod 44 mark 51 and the beam 54 are longitudinally aligned with the dose end position 76 corresponding to the 0.2 ml dose volume. The plunger rod 44 position here is 87. When the user depresses the plunger rod 44, the plunger rod 44 translates axially until the stop surface 53 reaches the dose end position 76. At the same time, the beam 54 deflects onto the surface 79. The surface 90 of the beam 54 is axially constrained by the surface 78 in the non-patient direction. The user rotates the dose setting dial 47 to set a 2.0 ml dose until the rotational position corresponding to the dose end position 76 of the 2.0 ml dose is longitudinally aligned with the stop surface 53 of the plunger rod 44.

[0233] To protect the syringe 9 incorporated into the device, it may be necessary to include a cap. Furthermore, to minimize the risk of needle stick injuries and comply with regulations (or to facilitate injection at home), it is desirable to incorporate a safety mechanism to protect the needle after use. Fig. 27 An exemplary cover 91 is shown. The syringe cover 91 can be an extension of the housing 45, with diametrically opposed windows 94 to enable the user to check the drug in the syringe 9 before injection. The needle safety clip 92 pivots about the hinge 95. When the user receives the device with the enclosed drug, the needle safety clip is aligned as shown in "a". When the cap 93 is removed (as shown in "b"), the elastic beam 98 moves the needle safety clip 92 in the direction 99. Surface 96 ensures that the insertion angle of the needle 97 is perpendicular to the injection site to ensure the correct depth of insertion of the exposed needle. Once the injection is fully administered and the device is removed from the injection site, the user can push the needle safety clip 92 in the direction 99' until it is locked with the needle 97 (shown in "c"). The tip of the needle 97 is now fully enclosed in the safety clip 92. Fig.28 The latch 100 shown captures the needle 97 to prevent exposure to a used needle 97.

[0234] and Figure 2 The syringe 100 shown is different, and the syringe 43 comprises the sequential deployment of fine resolution and coarse resolution.The syringe 43 described in the text first relates to higher resolution, and then is the various dosage levels (coarse resolution) limited by the dosage end position 76.The syringe 43 is also illustrated as having 10 dosage volume levels in this article.However, various embodiments comprising being less than 10 or more than 10 dosage levels are included in the scope of the present disclosure.

[0235] According to various embodiments, the coarse resolution can be deployed before the fine resolution of the plunger rod 44 travels. This is relevant in applications where the delivery catheter has a large dead zone, for example, for delivery using a catheter tube, the dose volume is very small relative to the volume required to irrigate the catheter. In this case, when the dose setting dial, such as 47, is set to the irrigating position, the dose end position 76 (whose distance corresponds to the stroke required for the irrigating volume) is longitudinally aligned with the stop surface 53 of the plunger rod 44. This irrigating stroke is a coarse resolution. At the end of the irrigating stroke, the beam 54 is not locked. There is also no spline 71, allowing the dose dial 47 to be rotated at the end of the irrigating to set the desired dose volume. The axial position of the dose end position 76 for small doses provides fine resolution.

[0236] Likewise, embodiments are envisioned where it is desired to deliver several equal or unequal volumes sequentially. This can be achieved by removing the splines 71 in the dose setting dial 47 in the syringe 43, which are removed to enable sequential delivery of several equal or unequal volumes.

[0237] The various embodiments described above have fine and coarse resolutions encoded into the dose setting dial 47. According to various embodiments, Fig.29 A syringe 101 is shown in where fine and coarse resolutions are encoded onto the plunger rod 102 and a stop surface on the dose setting dial 103 that is the opposite of embodiment 43 .

[0238] The syringes 100 and 43 discussed above may have fine and coarse resolutions for dose volume and plunger rod travel encoded onto the dose setting dial. Alternatively, fine and coarse resolutions for dose volume and plunger rod travel may be encoded onto the plunger rod, as described below with respect to Fig.29 The embodiment shown includes a pre-filled syringe 9 filled with an injectable drug 8, which is closed by an elastic plunger stopper 7. The syringe has a pre-attached (fixed) needle 97 as a delivery conduit. The filled syringe is fixed to the device using a clip 14 and an elastic x-ring 15. Embodiment 101 shows a minimum of 0.2 ml and a maximum of 2.0 ml delivered, with an increment of 0.2 ml, for a total of 10 dose volume levels.

[0239] Fig.29 The plunger rod 102 of the embodiment in the embodiment includes a patient end 111p and a non-patient end 111np (see Fig.30). The user depresses the disc 111np axially to administer the dose. The plunger rod 102 includes a cylindrical fine resolution peg 109 and a plurality of pegs 110 corresponding to different dose volumes that can be set and injected using the device 101. Peg 110a corresponds to the lowest deliverable dose volume and peg 110c corresponds to the highest deliverable dose volume. Fig.30 Also shown are axial slots 112d and 112a, both of which help prevent the plunger rod 102 from rotating during operation of the device. Slots 112b and 112c help improve the manufacturability of the plunger rod 102. Surface 110s of the plug 110 is associated with the end of dose. Surface 100l of the plug 110 is associated with the axial locking of the plunger rod 102 in the non-patient direction after the end of dose. Fig.31 1 shows modifications to the plunger rod 102 within the scope of the device 101. The fine resolution peg 109a can have a flat surface, and the patient end 111p-a of the plunger rod 102 can have a flat surface that contacts the plunger stop 7 (eg, Fig.31 This end of the plunger rod may have other modifications to engage with the plunger stop 7.

[0240] According to various embodiments, the dose setting dial 103 is characterized by Fig.32Detailed in . The dose setting dial 103 comprises a rotatable body comprising a first stop having a surface 118a defining a dose delivery start position of the plunger rod 102 and a second stop having a surface 122a defining a dose delivery end position of the plunger rod 102. The dose setting dial 103 may comprise three sections - user contact and dose setting 113, dose volume reference 114 and end of dose device 115. Indicia 116 are printed on the cylindrical portion 114 to provide a visual aid to the user of the dose volume to be set. The dose setting dial 103 has an axial cavity 117 in which the plunger rod 102 is placed. The end of dose device 115 comprises a portion of a cylinder 114s having features on a cylindrical surface extending radially towards the axis of the dose setting dial 103. Through side slots 118 and 119 are present on the cylinder 114s. The slot 118 engages the fine resolution peg 109 (or 109a). Surface 118a contacts a surface on the peg 109 on its non-patient side. The slot 119 is divided by a beam 120 into a primary end of dose slot 121e, a start of dose slot 121s and a secondary end of dose slot 122. When the user selects and sets a dose volume for injection, the peg 110 corresponding to the selected dose volume on the plunger rod 102 is longitudinally aligned with the slot 121e. Except for the lowest dose volume setting and in all other dose volumes set by the user, the peg 110 corresponding to the dose just below the user selected dose is longitudinally aligned with the secondary end of dose slot 122. At the end of delivery of the aforementioned user selected dose volume, the aforementioned peg corresponding to the immediately lower volume is contained and constrained within the secondary end of dose slot 122 and is axially constrained by surface 122a. The beam 120 is deflected by the peg corresponding to the selected dose volume just before the end of the dose and then returns to the secondary end of dose slot 122. Fig.32 The position shown provides an audible end-of-dose indication. The user is able to rotate the dose setting dial 103 by manipulating the user contact and dose setting segments 113. The bottom of the dose setting dial 103 has features for controlling and aligning the dose setting dial. The rectangular groove segments 124 each correspond to a different dose volume that can be set using this embodiment; there is also a rectangular groove segment 124a corresponding to the "→" mark 116. Groove 124b corresponds to the lowest injection volume (0.2 ml), while groove 124c corresponds to the highest injection volume (2.0 ml) that can be set in the embodiment 101 shown here. The circular groove segment 123 covers the cumulative rotation angle of the dose setting dial 103 between the lowest dose volume and the highest dose volume, that is, the angle between 123b and 123c. 123a corresponds to the position of the "→" mark 116. The inclined surface 125 enables the beam 138 on the housing 105 to traverse from the inside of the groove starting from 123a to the outside of the groove. The interaction between surfaces 118 and 109 is similar to Figure 2The coarse dose setting interaction between the pin 110 and the surface 122a is similar to Figure 2 Features 18 and 31 of the embodiment described herein.

[0241] Fig.33 1 shows various views of the beam 120 through the multiple parts forming the dose setting dial 103. Surface 120a contacts the plunger rod 102. The protrusion 120-1 on the beam 120 helps to axially constrain the bolt 110 (and therefore the plunger rod 102), which corresponds to the dose volume setting for injection in the non-patient direction. At the end of dose delivery, the bolt 110 corresponding to the dose volume setting and the beam 140 of the dose end barrel 106 are constrained between surfaces 120b and 121a. Before the dose is about to end, the ramp feature on 120-1 enables the beam 140 to deflect the beam 120 from "b" to "a". After the bolt 110 corresponding to the dose volume setting has reached the end-of-dose position, the beam 120 relaxes back to position "a", and the surface 120b locks the retraction of the plunger rod 102. This also produces an audible sound indicating the end of the dose. For all dose volumes except the lowest dose volume, the peg 110 corresponding to the volume just below the set volume is axially constrained between surfaces 120c and 122a at the end of the dose. For all dose volume levels except the lowest settable volume, the peg 110 also deflects the beam 120 from "d" to "c" just before the end of the dose. Once the end of the dose is reached, the peg 110 disengages from the beam 120, allowing it to relax back to position "d", which also produces an audible indication of the end of the dose.

[0242] According to various embodiments, the cover 104 is Fig.34 104. The cutout 126 on the cover 104 provides a window only for the dose markings 116 corresponding to the dose volume set by the user. Other markings are obscured by the rest of the cover 104. Slots 127c provide the user with access to the segments 114 of the dose setting dial 103, which enables the user to rotate the dose setting dial 103 in order to set the dose volume. To facilitate attachment to the housing 105, the cover 104 has a plurality of cylindrical posts 128p. Slots 129c together with the same slots 129h in the housing 105 allow placement and axial restraint of the disc 107. Anti-rotation feature 112a The plunger rod inclined slot 131c is used to engage the tab 40 of the clip 14 for attaching the syringe 9 in the same manner as the previously disclosed embodiment. 132c is used to engage features in the dose end barrel 106. The dose end barrel is visible through the slot 133. Semicircular transverse slots 134c are also incorporated into the cover 104 to help attach the needle shield device.

[0243] According to various embodiments, the housing 105 is Fig.35131c. Slot 129h is complementary to slot 129c to ensure placement and axial restraint of disc 107. Similar to slot 131c, 131h is used to engage one of the tabs 40 of the clip 14 used in the attachment of the syringe 9. During assembly, the tabs 40 of the clip 14 are axially aligned with the axial keyway 135 until they reach the slots 131h and 131c. The clip 14 is twisted until the syringe 9 is tightly fixed to the housing 105. Slot 132h is identical and complementary to slot 132c on the cover 104. The semicircular transverse slot 134h can help attach a needle shield device. The housing 105 also includes two symmetrical slots 136 that cross each other radially to allow the user to check the drug 8 in the syringe 9 before injection. Features 136a and 136b are formed by the intersection of the slot 136 and the axial keyway 135. The latch beam 137 interacts with the rectangular groove segment 124 on the dose setting dial 103. The surfaces 137a and 137c are angled so that they can transition in and out of the rectangular groove segment 124 depending on the rotation direction of the dose setting dial 103. Each time the latch beam 137 transitions into the rectangular groove segment 124, the user hears an audible sound and provides tactile feedback to the user. When the latch beam 137 is contained within the rectangular groove segment, the user can see the corresponding dose marking 116 through the cutout 126 on the cover 104. For example, when the latch beam 137 is contained within the rectangular groove segment 124a, "→" is visible through the cutout 126. In addition, when the latch beam 137 is contained within the rectangular groove segment 124b, "0.2" is visible through the cutout 126. In addition, in this example, when the latch beam 137 is contained within the rectangular groove segment 124c, "2.0" is visible through the cutout 126. The latch beam 138 is disposed within the circular groove segment 123. Upon first receipt by a user, the latch beam 138 is positioned so that the surface 138a contacts the edge 123a; at the same time, the "→" marking 116 is visible through the cutout 126. The surface 138a ensures that the user's rotational input to the dose setting dial 103 can be applied only in the direction of the ramp 125 to 123b by deflecting the latch beam 138. Once the surface 138a is located at 123b, the "0.2" portion of the marking 116 is visible through the cutout 126. Once located at 123b, the latch beam returns to its undeflected state and the surface 138a prevents the dose setting dial 103 from rotating in the direction 125. The rotation angle between 123a and 123b is the same as the rotation angle between the "→" and "0.2" markings 116. Therefore, the surface 138b prevents the dose setting dial 103 from transitioning from "0.2" to "→". After the transition from "→" to "0.2", the dose setting dial 103 is allowed to continue to rotate until the surface 138c contacts 123c, at which point the "2.0" (maximum deliverable dose of the illustrated embodiment) marking 116 is visible through the cutout 126. The dose setting dial 103 can be rotated in either direction except when the latch beam 138 is located at 123b and 123c.The interaction between the surface 138 c and the surface through the edge 123 c prevents the transition from “2.0” to the “→” marking 116 on the dose setting dial 103 .

[0244] The end-of-dose cartridge 106 is Fig.36 104 and housing 105, respectively. A colored band 139 is printed on the outer cylindrical surface of the end-of-dose barrel 106; this band 139 provides a visible end-of-dose indication to the user and is visible to the user at the end of the dose through the slot 133 on the cover 104. The inner diameter of the end-of-dose barrel 106 defining the cavity 117 is slightly larger than the segment 115 on the dose setting dial 103, and its outer diameter is smaller than the diameter of the segment 114 of the dose setting dial 103. The end-of-dose barrel 106 is placed coaxially with the dose setting dial 103. The radially inwardly directed beam 140 is disposed in the slot 121s of the dose setting dial 103 at the start of a dose; this rotatably keys the end-of-dose barrel 106 to the dose setting dial 103. When the patient-facing side of the plug 110 corresponding to the dose volume set by the user is axially advanced toward 121a of the dose setting dial 103 to deliver the dose, the beam 140 is advanced from the slot 121s to the slot 121e. At the end of the dose, the beam 140 is located between the plug 110 and the surface 121a. This axial translation causes the hemispherical plug on the beam 141 to be released from the slots 132c, 132h and makes the colored band 139 visible to the user through the slot 133 on the cover 104 at the end of the dose. This method of indicating the end of the dose to the user is the same regardless of the injection volume. This provides consistency in conveying information to the user. It is conceivable that the end of dose barrel 106 may alternatively be a portion of a cylinder.

[0245] Fig.37 A disk 107 is shown that can be placed in 129c and 129h. It includes a radially inwardly directed protrusion 143 that is placed in the slot 112d of the plunger rod 102. The protrusion 143 helps prevent rotation of the plunger rod 102. The X-ring 15 is placed around the cylindrical feature 142. When assembled, the plunger rod 102 is placed in the cavity 117.

[0246] Fig.38 Two optically clear window covers 108 are shown attached to slots 136. Window covers 108 are attached to housing 105 by first placing feature 143 into 136a of housing 105 and then placing clip 142 into 136b, locking it and covering slots 136.

[0247] According to various embodiments, Fig.39 In FIG. 1 , the assembled syringe 101 without its cap 104 is shown as 101 ′.

[0248] According to various embodiments, Fig.40 A partial external view of a dose setting using embodiment 101 is shown in FIG. "a" corresponds to the view when the user receives the embodiment. The axial position of the plunger rod 102 is marked as 144. When the user rotates the dose setting dial 103 to obtain "b" (0.2ml), "c" (0.4ml), "d" (0.8ml), "e" (1.0ml), "f" (1.8ml) or "g" (2.0ml), the axial position of the plunger rod 102 changes to 145. However, this axial position 145 is the same regardless of the dose volume setting for "b", "c", "d", "e" or "f". The axial translation from 144 to 145 is a fine resolution of the plunger rod 102 stroke, followed by a coarse resolution of the plunger rod 102 stroke.

[0249] exist Fig.41 The relative positions of the plunger rod 102 and the dose setting dial 103 after the initial translation facilitated by the fine resolution stroke are shown in b'. The fine resolution stroke is completed when the surface 118a axially advances the peg 109a to the position shown in b'. B' corresponds to a 0.2 ml dose volume starting dose in the illustrated embodiment. Upon further rotation of the dose setting dial 103 as shown in c', the peg 109a is placed behind the maximum inner diameter of the segment 114, but at the same axial position as b'. Continuous rotation of the dose setting dial 103 produces views d', e', f' and g', in which the peg 109a is positioned in its axial position shown in b' and c'.

[0250] Dose setting and dose delivery for 0.2 and 2.0 ml dose volumes Fig.42, illustrating the interaction between the dose setting dial 103 and the plunger rod 102. The position of the dose setting dial 103 relative to the plunger rod 102 before dose setting is shown by "a". Once the dose setting dial 103 is rotated to set a dose volume of 0.2 ml (shown in "b"), the plunger rod 102 advances from axial position 144 to position 145; this is a fine resolution stroke that helps overcome the static friction of the plunger stop 7 in a controlled manner. At the same time, the peg 110a on the plunger rod 102 is longitudinally aligned with the stop surface 121a. After the user axially advances the plunger rod 102 to administer the 0.2 ml set dose as shown in "c", the axial position 146 of the plunger rod 102 is the end-of-dose position. Simultaneously with this end-of-dose position 146, the peg 110a is in 121e. Between the patient-facing side of the peg 110a and the stop surface 121a is the beam 140 of the end-of-dose barrel 106 (not shown here for visibility). "d" describes the configuration when setting a 2.0 ml dose (the maximum dose of the illustrated embodiment). The axial position 145 of the plunger rod 102 at the start of the dose is the same in "d" as in "b". The pegs 110c and 110b on the plunger rod are longitudinally aligned with the stop surfaces 121a and 122a of the dose setting dial 103, respectively. After the user axially advances the plunger rod 102 to administer a 2.0 ml set dose as shown in "e", the axial position 147 of the plunger rod 102 is the dose end position. Simultaneously with this dose end position 147, the peg 110c is in 121e. Between the patient-facing side of the peg 110c and the stop surface 121a is the beam 140 of the dose end barrel 106 (not shown here for visibility). Moreover, at this time, the peg 110b is axially constrained in the cavity 122 and contacts the surface 122a. The cavity 122 is empty only in the case of the lowest dose volume (0.2 ml in the illustrated example). For all other doses, the cavity 122 constrains the peg 110 on the plunger rod axially and rotationally, which corresponds to a volume just below the level set for injection.

[0251] In some applications it may be desirable to shield the view of the needle before and after an injection. Embodiment 148 shows one such example in which a needle shield 149 shields the view of the injection needle 97. The needle shield 149 is guided into the track 135 of the housing 105. An end-of-process indicator barrel is contained within the needle shield 149. When the needle shield 149 is pressed against the injection site to insert the shielded needle 97, the needle shield 149 rotates a slide 150 when retracted into the housing 105, which includes a track for guiding features on the needle shield 149. The slide 150 is axially constrained within the slots 134c and 134h. After the injection process is completed, the spring 152 pushes the needle shield 149 to cover the needle 97 and axially locks the needle shield 149 due to the locking features on the slide 150.

[0252] For the purpose of explanation, the above description has been described with reference to specific embodiments. However, the above illustrative discussion is not intended to be exhaustive or to limit the invention to the precise form disclosed. In view of the above teachings, many modifications and variations are possible. The embodiments are selected and described in order to best explain the principles of the technology and its practical application. Thus, other persons skilled in the art can best utilize the technology and various embodiments with various modifications suitable for the intended specific use.

[0253] 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 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 defined by the claims. Finally, the entire disclosures of the patents and publications mentioned in this application are incorporated herein by reference.

[0254] The present invention further includes the following:

[0255] 1. A plunger rod assembly for a syringe, comprising:

[0256] main body;

[0257] a plunger rod at least partially received in the body and comprising a set of one or more protrusions; and

[0258] A dose setter operably coupled to the plunger rod and comprising a rotatable body including a set of one or more stops for engaging the set of one or more projections of the plunger rod at least in accordance with a rotational position of the set of one or more stops relative to the set of one or more projections, wherein a first rotational adjustment device associated with the dose setter is configured to adjust the relative axial position between the rotatable body and the plunger rod, and a subsequent rotational adjustment device associated with the dose setting assembly is configured to set a dose increment by adjusting the relative rotational alignment between the set of one or more stops and the set of one or more projections.

[0259] 2. The plunger rod assembly of claim 1, wherein the first rotational adjustment device comprises a rotatable dial that engages the rotatable body and is rotatable relative to the rotatable body to cause the rotatable body to translate axially relative to the main body.

[0260] 3. The plunger rod assembly of claim 2, wherein the rotatable dial comprises threads that engage threads of the rotatable body.

[0261] 4. The plunger rod assembly according to any one of clauses 1 to 3, wherein the subsequent rotation adjustment means comprises a second dial for rotating the rotatable body.

[0262] 5. The plunger rod assembly of clause 4, wherein the rotatable body is capable of translating relative to the second dial.

[0263] 6. The plunger rod assembly according to any one of clauses 1 to 3, wherein the subsequent rotational adjustment device receives the same dial as the first rotational adjustment device.

[0264] 7. The plunger rod assembly according to any one of items 1 to 3, wherein the first rotation adjustment device adjusts the axial position of the plunger rod relative to the body.

[0265] 8. The plunger rod assembly according to any one of clauses 1 to 3, wherein the plunger rod is rotationally fixed.

[0266] 9. The plunger rod assembly according to any one of items 1 to 3, wherein the rotation axis of the rotatable body intersects the plunger rod.

[0267] 10. The plunger rod assembly of any one of clauses 1 to 3, wherein the set of one or more protrusions comprises a single protrusion and the set of one or more stops comprises a plurality of stops.

[0268] 11. The plunger rod assembly of any one of items 1-3, wherein the set of one or more protrusions comprises a plurality of protrusions and the set of one or more stops comprises a single stop.

[0269] 12. A plunger rod assembly according to any one of items 1-3, wherein the first rotation adjustment device includes a narrow groove in the rotatable body for receiving a portion of the plunger rod, and the narrow groove includes an inclined surface, which axially pushes the portion of the plunger rod received in the narrow groove when the rotatable body rotates.

[0270] 13. The plunger rod assembly of clause 12, wherein the set of one or more protrusions comprises a single protrusion, and the portion of the plunger rod is the single protrusion.

[0271] 14. A plunger rod assembly according to item 12, wherein the portion of the plunger rod is disengageable from one circumferential end of the narrow slot so that continued rotation of the rotatable body does not cause further axial translation of the plunger rod relative to the rotatable body.

[0272] 15. A method of defining a fluid volume using a prefilled syringe, the method comprising:

[0273] applying a first rotational input to a dose setter of the syringe to adjust a relative axial position between at least a portion of the dose setter and a plunger rod of the syringe; and

[0274] applying a subsequent rotational input to the dose setter of the syringe to adjust the rotational position of the at least a portion of the dose setter to set a dose increment,

[0275] The start of the dose axial position of the plunger rod is the same for different dose settings.

[0276] 16. A method according to clause 15, wherein the first rotational input is applied to a rotatable dial and causes an axial translation relative to the plunger rod.

[0277] 17. A method according to clause 16, wherein the second rotational input is applied to a dial which is translationally fixed relative to the plunger rod and rotationally coupled to the at least a portion of the dose setter.

[0278] 18. A method according to clause 15, wherein the first and second rotational inputs are applied to a dial of the at least a portion of the dose setter.

[0279] 19. A method according to any one of items 15-18, wherein applying the first rotational input causes the plunger rod to be axially advanced relative to the barrel of the syringe.

[0280] 20. A method according to any one of items 15-18, wherein at least a portion of the dose setter includes at least one stop, the plunger rod includes at least one protrusion, and adjusting the rotational position of at least a portion of the dose setter includes aligning the at least one stop with the at least one protrusion.

[0281] 21. The method of any one of clauses 15-18, further comprising constraining the dose setter after delivering the dose.

Claims

1. A plunger rod assembly for a syringe, include: main body; a plunger rod at least partially received in the body and including a set of one or more protrusions; as well as A dose setter operably coupled to the plunger rod and comprising a rotatable body comprising a set of one or more stops for engaging the set of one or more projections of the plunger rod at least in accordance with a rotational position of the set of one or more stops relative to the set of one or more projections, wherein a first rotational adjustment device associated with the dose setter is configured to set a first dose increment by adjusting a relative axial position between the rotatable body and the plunger rod, and a second rotational adjustment device associated with the dose setting assembly is configured to set a second dose increment greater than the first dose increment by adjusting a relative rotational alignment between the set of one or more stops and the set of one or more projections.

2. The plunger rod assembly of claim 1, wherein the first rotational adjustment device comprises a rotatable dial that engages the rotatable body and is rotatable relative to the rotatable body to axially translate the rotatable body relative to the main body. 3 . The plunger rod assembly of claim 2 , wherein the rotatable dial includes threads that engage threads of the rotatable body.

4. The plunger rod assembly according to any one of claims 1 to 3, wherein the second rotation adjustment device comprises a dial for rotating the rotatable body.

5. The plunger rod assembly of claim 4, wherein the rotatable body is translatable relative to the dial.

6. The plunger rod assembly of claim 4, wherein the rotatable body and the dial are fixed relative to each other.

7. The plunger rod assembly according to any one of claims 1 to 6, wherein the first rotation adjustment device adjusts the axial position of the rotatable body relative to the main body.

8. The plunger rod assembly according to any one of claims 1 to 7, wherein the first rotation adjustment device adjusts the axial position of the plunger rod relative to the body.

9. The plunger rod assembly of any one of claims 1-8, wherein the plunger rod is rotationally fixed.

10. The plunger rod assembly of any one of claims 1-9, wherein the rotatable body is laterally offset relative to the plunger rod.

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