WO2024180081A1

WO2024180081A1 - Controlled dose syringe

Info

Publication number: WO2024180081A1
Application number: PCT/EP2024/054985
Authority: WO
Original assignee: Dunne, Stephen Terence
Priority date: 2023-02-28
Filing date: 2024-02-27
Publication date: 2024-09-06

Abstract

A syringe system (1) for delivering a drug or medical formulation into the body of a patient, comprising a hollow needle (200) positioned at a distal end (113) of a housing, and an actuator provided for manual operation by a user, wherein said actuator is mechanically coupled to the interior of said needle (200) by a plunger system, shall be provided that is particularly suitable for delivering micro doses of said drug or formulation. In accordance with the invention, this is achieved by that said plunger system comprises an actuator plunger rod (118a, 144a, 306) and a delivery plunger rod (118b, 128, 144b) mechanically coupled to said actuator plunger rod (118a, 144a, 306) by a transmission system, wherein said transmission system converts a stroke of said actuator plunger rod (118a, 144a, 306) into a stroke of said delivery plunger rod (118b, 128, 144b) at a predetermined conversion ratio.

Description

Specification

Controlled Dose Syringe

The invention relates to a syringe system, in particular an accurate or micro dose manually operated syringe system. More specifically, the invention relates to a syringe system for delivering a drug or medical formulation into the body of a patient, comprising a hollow needle positioned at a distal end of a housing or attachable to said distal end, and an actuator provided for manual operation by a user, wherein said actuator is mechanically coupled to the interior of said needle or said distal end by a plunger system.

Glass and plastic pre-filled syringes or ready-to-fill syringes are supplied for use with the drug formulation already in the syringe and ready to use. There are two formats. The first has a Luer connection for attaching a hypodermic needle. The second format, the staked needle syringe, has the needle already attached. Both formats need to be lubricated with silicone oil to facilitate stopper or piston travel.

An alternative to pre-filled syringes are cartridges that comprise of a glass or plastic barrel, a pierceable septum held by a crimped metal ferrule at one end and a stopper/piston at the other. A septum piercing needle or cannula is used to perforate or pierce the septum making a fluid pathway between the cartridge drug contents and the injection needle or connecting port. Such arrangements are typically used in pen injectors such as insulin pens and cartridge-based dentistry syringes.

Both pre-filled syringes have moving pistons or stoppers that can be attached to a plunger rod having a plunger flange at the end which is designed to be manually pushed usually by the thumb in order to deliver the liquid formulation or drug.

Cartridges are available in both ready to fill and much cheaper bulk formats. They can be filled like syringes by capping, filing, and stoppering or bubble free by stoppering, filling and caping. Some injections and in particular ophthalmic injections require very small dose volumes and can be as small as 20 microliters. Conventional syringes, however, are of limited use for delivery of such small quantities since they require a very careful handling for proper dosage.

It is therefore an object of the present invention to provide a syringe that is particularly suitable for delivering such micro doses. In particular, a syringe should be provided that can be used with various drug containers including cartridges and pre-filled syringes, for delivery of particularly small doses.

In accordance with the invention, this objective is achieved with a syringe system as defined in claim 1.

More specifically, in accordance with one aspect of the invention, the object identified above is achieved with a plunger system comprising an actuator plunger rod and a delivery plunger rod mechanically coupled to said actuator plunger rod by a transmission system, wherein said transmission system converts a stroke of said actuator plunger rod into a stroke of said delivery plunger rod at a predetermined conversion ratio.

Preferred embodiments of the invention are defined in the dependent claims.

The invention is based upon the consideration that small dose volumes typically require a very small displacement of the stopper or the plunger driving the stopper, in the barrel of the syringe or, alternatively, in the pre-filled cartridge. In order to allow for such particularly small displacements on the delivery side of the syringe, a proper and relatively easy to handle actuation of the driving plunger in accordance with an embodiment of the invention may be achieved by providing a transmission system between actuator and stopper/ plunger that converts a stroke applied to the actuator by the user to a relatively smaller displacement of the plunger or stopper for the actual drug deliver. In particular, the axial plunger flange movement in accordance with an embodiment of the invention may be larger than the stopper axial movement.

In particular, a syringe system in accordance with aspects of the present invention may comprise one or more of: A syringe housing with finger pads or flange or finger rings at the proximal end and an injection port at the distal end capable of firmly holding; a drug container with drug delivery means at the distal end of the barrel and a stopper/pis- ton disposed near the proximal end of the barrel to contain the medicament or other formulation between the distal and proximal ends, a mechanical advantage mechanism comprising of a pivoted lever that translates the axial movement of an actuation plunger rod into a smaller axial movement of a delivery plunger rod and where the mechanical advantage mechanism is held in a movable housing that is free to move axially relative to the syringe housing from a first position to a second position where it is locked into the second position; an actuation plunger rod with finger pad at its proximal end and initially in communication at its distal end with the movable housing of the mechanical advantage mechanism; a delivery plunger rod with its proximal end attached to the pivoted lever of the mechanical advantage mechanism and its distal end in contact with but not attached to the container stopper; where when pressed by the user the actuation plunger rod causes the axial movement from the first to a second position of the movable housing axially displacing the delivery plunger rod readying the syringe system for the injection and where; when used with a cartridge; a septum needle is rigidly held in the syringe housing and is in fluid communication with an injection port projecting from the distal end of the syringe housing and where the cartridge is held axially in a first position and is prevented from substantially moving unaided axially forwards within the syringe housing and where the movement of the mechanical advantage mechanism movable housing pushes the delivery plunger rod and cartridge from first position to a second position where the septum needle perforates the septum and thereafter pushes the cartridge stopper priming the syringe system; or a threaded fitting including means to connect an injection needle and septum needle combination projecting from the distal end of the syringe housing and where the cartridge is held axially in position and is prevented from moving axially within the syringe housing and where after the user attaches the double needle perforating the septum the movement of the mechanical advantage mechanism movable housing pushes the delivery plunger rod and stopper priming the syringe system; and when used with a pre-filled syringe; the pre-filled syringe and/or the injection port projects from the distal end of the syringe housing and the pre-filled syringe is held axially in position and is prevented from moving axially within the syringe housing and where the movement of the mechanical advantage mechanism movable housing pushes the delivery plunger rod and stopper priming the syringe system; where after priming the device the movable housing is locked into its second position at the second position and unable to travel further axially whereupon the actuation plunger rod is rotated allowing the actuation plunger rod to communicate with and push axially against the pivoted lever whereafter when the actuation plunger rod is pressed a precise dose of the contents of the container are expelled through the injection port determined by the axial movement of the delivery plunger rod where the axial movement of the delivery plunger rod is determined by the movement of the pivoted lever and its precise external dimensions and shape.

In one aspect, considered independently inventive, the transmission system may comprise a conversion lever. In this embodiment, the conversion lever preferably may be mounted in a housing pivotable about an axis such that the actuator plunger, for driving rotation of said conversion lever around said axis, engages said conversion lever at a driving offset with respect to that axis, and said delivery plunger is positioned for engagement by said conversion lever at a receiving offset with respect to said axis. In such design, predefined stroke ratios may be provided in a highly reliable and highly precise way. This preferred embodiment in particular allows for high conversion rates for the stroke, thus enabling very small displacements of the delivery plunger rod at “regular” displacements of the actuator plunger rod, thereby allowing reliable delivery of particularly small doses.

In an aspect of the invention according to this embodiment, the conversion lever preferably may be profiled, having a number of flat surfaces and a number of curved surfaces, wherein, after completion of the intended rotation of the conversion lever, the conversion lever may come to rest in a position in which a first of the flat surfaces abuts a flange of the actuation plunger. A second of said flat surfaces then may abut on a flange of said delivery plunger. In a preferred embodiment, considered independently inventive, the lever in this design may be configured such that the first, “upper” flat surface basically is parallel to the second, “lower” flat surface. This configuration, in the end position, provides “intrinsic stability”, in the sense that once the rotation of the lever reaches is designed end position and the flat surfaces are in contact with their respective counterparts, i. e. the flanges of the respective plunger rods, it can no longer rotate in the direction of rotation. Thereby, the rotation is self-limiting, so no additional stop is required. This is particularly useful for a “priming” design.

In yet another preferred embodiment, considered independently inventive, the transmission system is designed for first having a priming stroke of said actuator rod before an actual ejecting stroke for ejection of the drug or formulation out of said hollow needle is enabled. In such setup, ejection of the drug or formulation from within said hollow needle by said delivery plunger may be blocked until after said priming stroke has been executed. In particular, in one aspect the housing of the applicator system may comprise at least two housing components movable in relation to each other, wherein a priming stroke may be affected by moving two of said housing components relative to each other, in particular by. pushing two of said housing components together.

Preferably, in such an embodiment in which priming is desired, ejection of said drug or medical formulation from within said hollow needle by said delivery plunger rod is blocked until after said priming stroke has been executed.

If priming is not required, the mechanical advantage mechanism housing maybe fixed into position relative to the syringe housing or the mechanism may be fixed to the housing. In this case the user simply rotates to unlock if required and presses the plunger finger pad and injects the container contents via the mechanical advantage mechanism.

The pivoted lever may be a pivoted cam shaped element or a simple pivoted cantilever or any other pivoted lever.

There may be a tolerance gap between the mechanical advantage mechanism movable housing and the actuation plunger rod and the delivery plunger rod where it is allowed to freely and axially move. These tolerance gaps are taken up when the device is primed. The axial movement of the actuation plunger rod doesn’t determine the axial movement of the delivery plunger rod but its axial movement must be sufficient to fully rotate or pivot the pivoted lever from its first position to its second position. These two positions are determined by stops on the movable housing.

The injection port may be an injection needle for subcutaneous, intravitreal or other injection or it may be a connector such as a luer connector or other connector type where an injection needle or line may be connected.

Note that if the injection needle is fixed, to the syringe body or to the pre-filled syringe, the syringes can generally only be used sequentially on one subject or patient. If the device has a luer or threaded connection the needle may be replaced after each dose and can used sequentially with multiple patients or daily or with other intervals depending on the drug with single or multiple patients.

Once priming is done the syringe is used by first rotating the plunger rod and then inserting the needle into the injection site and pressing the plunger rod. The movement of the plunger rod is larger than the movement of the stopper giving better feedback to the user especially when very small doses are injected and where the stopper movement is less than 2mm or less than 1mm. The mechanical advantage is also very advantageous when viscous liquid are injected.

In the case of pre-filled syringes, the pre-filled syringe may be held by the shoulder at its distal end like a cartridge or by its flanges at its proximal end, in which case most of the syringe barrel can be exposed beyond a short syringe housing facilitating the viewing of the drug contents.

Where possible the user may replace the needle after each dose is delivered.

The cartridge or pre-filled syringe may be inserted before sterilization or by the user.

The cartridge or pre-filled syringe maybe be inserted axially or radially. When inserted axially the user attaches or positions the plunger rod after inserting the cartridge. When inserted radially or sideways the plunger rod may already be in place. The invention is generally a single use device where one container is used either supplied installed or inserted by the user. Some embodiments may be re-usable where more than one container can be used and in particular in the case of a cartridge base device where the septum needle is replaced along with the injection needle or in the case of a pre-filled syringe-based device where the needle is attached by the user. In both cases the drug containers are inserted by the user.

With a movable cartridge the cartridge may be held in the first position by a deformable or movable stop on the cartridge shoulder or cap to prevent the cartridge moving forward during transport or handling or after insertion by the user. The cartridge may be held or further held in place by friction or interference fit. The device may have a locking mechanism that holds the cartridge in place before use. If the device has a locking mechanism this needs to be unlocked so that the cartridge can be pushed to the second position by pressing the plunger rod. The lock may hold the deformable stops in the closed position that are released by activating a switch or button or other means such as removing a cap.

The device when used with a cartridge may include a cap to cover the injection needle or luer or other connection prior to use. In the case of a movable cartridge the cap may be used to lock the cartridge at the first position before use. This locking feature may be part of the cap or the housing in which case the lock is held in the locked position by the cap.

The drug container may be filled with or without an air or gas bubble. This can be expelled during priming before the first injection.

The drug container may be a double chamber or a dual chamber container. In this case the first axial movement is additionally used to mix the contents of the two chambers while the second axial movement may be used to prime and expel any air in the container. When the drug container is a cartridge and in particular a moving cartridge the first axial movement also moves the cartridge forwards wherein the septum is perforated by the septum needle before mixing takes place. The drug container contents may be a liquid and a dry powder or two liquids.

The whole assembly including with or without the drug container may be terminally sterilized in a blister or other outer packaging. Depending on the drug type and packaging and device materials the system can be sterilized using moist heat (steam), dry heat, gamma radiation or other radiation, ethylene oxide gas, vaporized hydrogen peroxide, chlorine dioxide gas, vaporized peracetic acid or nitrogen dioxide. When terminally sterilized with the drug container in place the terminal sterilization may be adjusted to only sterilize the outside surfaces of the syringe and the drug container. However, it can also be adjusted and be used to additionally sterilize the drug contents themselves if required.

Further it must be noted that the present invention may be terminally sterilized with a prefilled syringe containing the drug formulation with a Luer connector and with an accurate fixed injection dose as low as 10 microliters. This feature is quite unique to the present invention.

The drug container barrel may be made of glass or plastic such as COC or COP. The syringe system may be adapted for subcutaneous, intramuscular, intradermal, ophthalmologic, intravascular, intravenous or any other type of injections.

The current invention may be used to deliver or inject any liquid into any body including human or animal for any purpose.

In another aspect of the invention, which is considered independently inventive, the syringe may by intended for ocular, intravitreal or intraocular injections where accuracy of dose is very important. For this application, preferably the small diameter 0,5ml pre-filled syringe, either staked needle or Luer version, may be used. The small diameter would give sufficient stroke length for feedback as the dose is around 20 to 50 microliters. Another big advantage of the present invention is that the user cannot inadvertently reverse the plunger rod travel eliminating the chance of air being sucked into the needle and injected into the eye.

The current invention may have an indicator either visual, audio or tactile to warn the user of the end of priming and/or dosing status.

The current invention is a great improvement over the use of vials and disposable syringes as far fewer user steps are required with less likelihood of clinical errors as no transfer of drug solution from vial to syringe is required.

The current invention is a great improvement over existing state of the art micro-dose delivery systems as it is of a simpler construction. The current invention in one aspect is a micro-dose syringe system which is elegant in its simplicity, and which is easy to implement that may be terminally sterilised along with the drug contents.

In particular, a syringe in accordance with the present invention may be terminally sterilized with a pre-filled syringe or cartridge containing the drug formulation capable of delivering an accurate fixed injection dose as low as 10 microliters. No transfer of drug solution from vial to syringe is needed even for very small injection doses. This feature is quite unique to the present invention.

Ocular pre-filled syringes are generally required to be terminal sterilized. If a pre-filled syringe is used, then only a Luer version may be used as staked needle pre-filled syringes cannot be sterilized because the needle is in contact with the syringe contents and sealed by a gas permeable cap. In use the user needs to attach a needle after removing the device from a sterile blister potentially loosing sterility.

In another aspect of the present invention a staked needle cartridge system is used which can be terminally sterilized as the injection needle is not in contact with the contents during sterilization but at the same time is an integral part of the device. This is a big advantage as the device is ready to use after removing from the sterile blister.

Various embodiments of the present invention, by way of example, are provided in the figures. Therein,

Figure 1a shows a ‘state of the art’ standard ISO 13926 Cartridge.

Figure 1 b shows a ‘state of the art’ standard ISO 11040 Luer pre-filled syringe.

Figure 2a shows a single dose, cartridge based, syringe generally as per

PCT/EP2022/075752 comprising a fixed septum needle and means to attach an injection needle or Luer.

Figure 2b shows a single dose, cartridge based, syringe generally as per the prior art with means to attach a double ended needle. Figure 3 shows the invention with an integrated precise multi dosing mechanism as apply to and for use with an axially movable cartridge in combination with a fixed septum needle.

Figures 4 show the transmission box details of the present invention with an integrated precise multi dosing mechanism for use with an axially fixed cartridge and means to receive a double ended needle.

Figures 5 show the transmission box details of the present invention with an integrated precise multi dosing mechanism for use with a pre-filled syringe.

Figures 6 show the transmission box details of the present invention with an integrated precise multi dosing mechanism for use with an axially movable cartridge in combination with a fixed septum needle.

Figures 7 show a pivoted lever or lever/cam with a self-limiting feature for use with the present invention.

Figures 8 show alternatives arrangements of the transmission box relative to the prefilled syringe or cartridge.

Figure 9 shows an alternative pivoted lever.

Figures 10 show a complete assembly of the present invention using a pre-filled syringe.

Figures 11 and 12 show an alternative complete assembly of the present invention using a pre-filled syringe.

Generally identical parts are provided with the same reference numbers in all figures. The invention will be explained below primarily with reference to the embodiments shown. Aspects mentioned below, separately or in combination with each other, may be considered independently inventive. However, other embodiments are of course also conceivable and covered by the present invention. Embodiments of the present invention include syringe systems 1 preferably suitable for use with pre-filled cartridges 110 or for use as pre-fillable syringes 110a.

In Figure 1a a cartridge 110 has a plastic or glass barrel 111 , an open proximal end 119 and a necked and flanged end 113b at a distal end 113 forming a shoulder 113a with the barrel 111. A movable stopper 112 at open end 119 and a rubber cap assembly 95 at the necked end or distal end 113 seal the drug formulation solution 117 within the barrel 111. Cap assembly 95 has a septum 114 which is held in place by a metal crimp or ferrule 115 which is in turn crimped to the cartridge neck 113. Ferrule 115 has a hole 116 to allow needle insertion through the septum 114.

Such cartridges are fully described in ISO 13926 and can have glass or plastic barrels.

In the following Figures the cap 95 may refer to the combination of a ferrule and a septum assembly as described in Figure 1a.

In Figure 1b a pre-fillable syringe 110a has a plastic or glass barrel 111a having an open proximal end 119a with a finger flange 121 and a necked end 113 forming a Luer connection 98 sealed by a shield 96 at the distal end 113. A movable stopper plunger 112a at open proximal end 119a and the needle shield 96 at the distal end seal the drug formulation solution 117 within the barrel 111a.

Figure 2a shows a basic single-dose syringe system of the prior art. A cartridge 110 is mounted within a housing or housing 127 at a first position. A Luer connection 123 as a means for attaching a hollow needle 200 is located at the distal end of the syringe housing. A septum needle 124 is firmly held at the front end or distal end of housing 127 and in fluid communication with a Luer or other connector 123 at the distal end of the housing 127. Cartridge 110 is axially free to move under user force in the direction of the septum needle 124 to a second position and when axially pushed by pushing plunger rod 128a at pad 129a it forces septum needle 124 to pierce the cartridge cap 95 thereby establishing fluid communication between the cartridge liquid contents and the Luer connection 123.

The user can push the plunger rod 128a using the thumb pad 129a and finger flanges 131 in the usual way to axially push the cartridge 110 to a second position to enable the syringe system and prime the system if required and perform the injection of contents 117 via Luer connection 123. Connection 123 maybe a Luer slip or a Luer lock for hypodermic needles or tubing.

Gas-access pathways 135 may be placed in housing 127 to facilitate gas sterilization of the needle assembly.

Cartridge 110 may be locked into place in the first position before use to prevent the cartridge septum being inadvertently pierced by needle 124. Alternatively, cartridge 110 may be held in the first position by friction and for instance by friction at the cartridge shoulder.

Figure 2a shows the embodiment where the cartridge 110 is movable from a first position to a second position and where the housing 127 has a septum needle 124 firmly attached. Where the cartridge 110 is fixed in position and the user attaches a double ended needle the cartridge is always fixed in the second position and a septum needle is not attached to the housing but there is a passageway to allow the double ended needle through. This is shown in Figure 2b.

In Figure 2b the Luer connection has been replaced with a screw fitting 123a including a hole or passageway 136 to allow the insertion of a septum needle. Cartridge 110 is fixed into position and unable to move axially. Such an arrangement can be used with state of the art dental and/or insulin double ended needles.

Figure 3 shows the basic concept of the present invention with an integrated precise multi dosing mechanism for use with a movable cartridge with fixed septum needle.

The plunger rod in accordance with one aspect of the invention is split into two parts; an actuation plunger rod 144a connected to a thumb pad 146 and a delivery plunger rod 144b connected to the cartridge stopper 112 where the two rods 144a and 144b are connected together via a transmission box 140. The transmission box 140 has a gearing arrangement where actuation plunger rod 144a travels a greater distance than delivery plunger rod 144b giving the user a better feel when very small volumes are injected with the corresponding very small movement of the stopper 112 and delivery plunger rod 144b.

In Figure 3 the device is shown with a cartridge 110. To prime, the cartridge 110 is moved forward so that septum needle 124 perforates septum 114 expelling air trapped in the needle and expelling any air trapped in the cartridge 110. Note that cartridge 110 is shown with a Luer slip connector 123 for receiving a hypodermic needle which is attached prior to priming the device.

Note that the same concept with a transmission box 140 can be applied to an axially fixed cartridge or an axially fixed pre-filled syringe.

Figures 4 show an embodiment of the present invention with an accurate dosing system. In Figures 4, only the mechanical advantage mechanism of the syringe system is shown, together with its relationship with the actuation plunger rod 306 and delivery plunger rod 128. The embodiment shown is for use with an axially fixed cartridge 110. A cartridge barrel 304 is held securely to a syringe main housing 302. An actuation piston rod 306 has an extension 306a off center and of small cross section. A movable housing 312 holds a pivoted lever or lever 321 pivoted at axis 321a. Travel stops 323 and 323a limit the rotational travel of pivoted lever 321. Movable housing 312 has hole 312a at its upper end and is fully open at its lower end.

In Figure 4a the movable housing 312 is in a first position and generally free to move between tolerance gaps 307 and 307a. In this position the syringe system is ready to use and the extension 306a is in axial line with the top of movable housing 312. To prime the device the user presses actuation plunger rod 306. This action pushes the movable housing 312 downwards against delivery plunger rod 128. The two tolerance gaps 307, 307a are closed and the pivoted lever 321 engages with delivery plunger rod 128. In accordance with aspects of the invention, pivoted lever 321 is prevented from pivoting by travel stop 323. Further pushing of the actuation plunger rod 306 causes delivery plunger rod 128 to move axially downwards priming the device by expelling some drug solution and any gas bubble. The delivery plunger rod travels by distance 331. The final resting position after priming is shown by Figure 4b where the movable housing 312 in accordance with yet another aspect of the invention is locked by lock 325 to prevent further movement at its second position. Note that to expel any gas bubbles the orientation as shown in Figures 3 would need to be reversed with the delivery plunger rod at the top.

After priming the user rotates the actuation plunger rod 306 until extension 306a is axially in line with movable housing hole 312a. This position is shown in Figure 4c. The user then simply pushes the actuation plunger rod again whereupon it pushes against pivoted lever 321 forcing it to pivot where its lower surface pushes against the delivery plunger rod 128. Tolerance gap 307b is closed when the actuation plunger rod 306 is first pushed. The distance travelled by the actuation plunger rod is 333 while the smaller distance travelled by the delivery plunger rod is 335 and the rotation of pivoted lever is stopped by stop 323a. The ratio of the two is the mechanical advantage. The ratio is a function of the shape and size of the pivoted lever 321 and the axial distance between stops 323 and 323a.

Figures 5 show an embodiment of the present invention with an accurate dosing system. The embodiment shown is for use with an axially fixed pre-filled syringe. The mechanism is the same as that described in Figures 4. The differences are:

The syringe barrel 304a has a flange 304b held in housing 302 by feature 302a. The stop 323a of Figures 4 is replaced by the movable housing 312 side wall and lock 325 of Figures 4 is replaced by allowing the movable housing to be held by the syringe barrel 304a at point 326 in a second position.

In both Figures 4 and 5 it can be seen that the tolerance gaps 307, 307a and 307b have no effect on the final axial travel distance of the delivery plunger rod 128 during the injection stroke and the tolerances are taken up by the actuation plunger rod 306 travel during the priming stroke. This ensures an accurate dose during the injection stroke defined only by the shape and size of the pivoted lever 321 and the axial distance between stops 323 and 323a or stop 323 and the movable housing side wall.

Figures 6 shows one embodiment of the present invention with an accurate dosing system. The embodiment shown is for use with a movable cartridge 110 and fixed septum needle 124 as described in Figure 3. The mechanism is the same as that described in Figures 4 except that during the priming stroke the movement of the delivery plunger rod 128 first pushes the whole cartridge barrel 304 into its second position where the cartridge septum is pierced to allow priming.

The cartridge housing may have an integral staked needle which can be terminally sterilized as the injection needle is not in contact with the contents during sterilization but at the same time is an integral part of the device. This is a big advantage as the device is ready to be used after removing from the sterile blister. Note that in Figures 4, 5 and 6 the pivoted lever 321 can alternatively be arranged to reverse the mechanical advantage with more axial movement of the delivery plunger rod 128 than the actuation plunger rod 306.

In Figures 7 another pivoted lever or lever/cam 801 is shown which has a self-limiting feature. Lever 801 if free to rotate as shown by arrow 802 and has three flat surfaces 831 , 833 and 835 and is pivoted at axel 811 with center 813. In Figure 7a the lever 801 is shown before injecting the accurate injection dose but after priming. An actuation plunger rod 803 has a flange 805 abutting on top of curved surface 837 of lever 801. The lower flat surface 835 of lever 801 abuts on flange 806 of delivery plunger rod 803.

In Figure 7b the lever 801 is shown after delivering the accurate injection dose. Lever 801 has been rotated as shown by 802 in Figure 7a by plunger rod 803 when pushed as shown by arrow 804. The flat surface 831 is now abutting the flange 805 of actuation plunger rod 803. The vertical centerline 817 of axel 811 passes through the actuation plunger rod 803 flange 805. Once the rotation of the lever 801 reaches the shown position it can no longer rotate in the direction of rotation 802. The rotation is self-limiting, so no stop 323 as shown in Figures 5 and 6 is required. This is a great advantage of this independently inventive embodiment as this eliminates another possible tolerance issue.

Such a lever 801 as described in Figures 7 in accordance with aspects of the invention may be used with the devices shown in Figures 4, 5 and 6.

Figure 8a shows a schematic of the invention where the mechanical advance mechanism 401 is held within the confines of housing 110b while in Figure 8b the mechanism 403 is held outside the confines of the housing 110c.

In Figure 8a a axially movable cartridge in combination with a fixed septum needle is shown while in Figure 8b a staked needle pre-filled syringe is shown. In must be noted that alternatively Figure 8a can be used with a pre-filed syringe and Figure 8b with an axially movable or a fixed cartridge.

In Figure 9 an alternative pivoted lever is shown. A beam and fulcrum arrangement or cantilever arrangement has a beam 451 pivoted at point 452. Beam 451 is shown in engagement with actuation plunger rod 306b at a horizontal distance 421 from pivot 452 and with delivery plunger rod 128b at horizontal position 423 which is closer to the pivot point 452. The beam or pivoted lever 451 is also held in position by stop 323c.

When pushed by actuation plunger rod 306b it pivots to position as shown by 453 and its travel is limited by the side wall of the movable housing or by a stop 333b. The distance travelled by the actuation plunger rod 306b is 425 and the distance covered by the delivery plunger rod 128b is 427. The ratio of the two is the mechanical advantage. The ratio is a function of the ratio of the pivot distances 421 and 423 of the pivoted lever 451 and the axial distance between stops 323c and 333b.

Figures 10 show one embodiment of the complete assembly of the current invention. Figure 10a shows the device from the outside while Figure 10b shown a cross section of the device rotated relative to Figure 10a by 90 degrees. Main housing 302 has a transmission housing 312 provided slidably within. Transmission housing 312 has within a pivoted lever 321. An actuation plunger rod 118a and a delivery plunger rod 118b are in communication with the lever 321.

A pre-fillable syringe 110a has a needle 200 attached to its distal end and a barrel 111a with a stopper 112 and contents 117 within.

Pre-fillable syringe 110a is attached to the outer housing 302 by its flange 121 and firmly held in position by a finger grip 126 by a thread 126a. Syringe 110a is shown with a hypodermic needle 200 attached. Syringe 110a may be a staked needle syringe where needle 200 is glued into syringe barrel 111a or it may have a Luer connector or other connector arranged to receive a needle 200.

A lock or key 142 prevents the actuation plunger rod 118a moving during handling and priming of the device. To prime the device thumb pad 120 is depressed by the user at which point the inner housing 312 travels relative to the outer housing 302 moving the delivery plunger rod 118b and hence stopper 112a filling the needle 200 with liquid contents and removing air in the needle 200 and any trapped air bubble in the syringe. At the end of the priming stroke inner housing 312 is held axially firmly withing outer housing 302 by interference fit or a lock or snaps or by any other means.

To inject the contents via needle 200 the user removes the lock 142 and presses thumb pad 120 which will cause the lever 321 to pivot and push lower lunger rod 118 and stopper 112a to deliver the exact volumetric dose. The dose volume is determined by the lever 321 dimensions.

Figure 11 shows an exploded view of the transmission housing of another embodiment of the complete assembly of the current invention. Main housing 302b has a transmission housing 312b within. Transmission housing 312b has within a pivoted lever 321. In Figure 11 the delivery plunger rod is not shown.

The embodiment of Figure 11 is only different to the embodiment shown in Figure 10 in that the transmission housing 312b has pin 314 that engages with an inner thread on the main housing 302b. To prime the device the transmission housing 312b is rotated by grip 313. To change the dose volume the lever 321 can be changed. For a 20 microliter dose lever 321d is used and for a 50 microliter dose lever 321e is used.

The embodiment of Figure 11 in accordance with aspects of the invention has advantages over the embodiment shown in Figure 10. In Figure 10 the end of priming is reached when the axial movement reaches interference fit or snaps. Because of tolerances it may be difficult to hold the transmission housing axially without any movement. Because the dosing stroke can be very small any axial movement of the transmission housing during dosing can lead to great dosing volume errors. In Figure 11 the transmission housing 312 is rotated within the main housing 302 coming to a tight fit at the end with no axial movement possible.

Figures 12 show the same embodiment as Figure 11. In Figure 12a the device is shown before use without a needle attached to Luer 123. Lock 142 is in place and the transmission housing 312a is fully extended from the main housing 302a. In Figure 12b needle 200 has been attached to Luer 123 and the device has been primed by rotating the transmission housing 312a by grip 313. The distance 171 travelled by the syringe stopper 112 is prime volume of contents 117 sufficient to purge any gas bubble in the syringe and fill the needle 200 with liquid. In Figure 12c the device has been used. Lock 142 has been removed and finger pad 120 has been pressed resulting in the rotation of lever 321 by actuation plunger rod 118a and the and the displacement of stopper 112 by amount shown by 169 delivering a precise dose of contents 118b to the injection site. List of reference numerals

1 syringe system

95 cap

96 shield

98 Luer connection

110 cartridge

110a pre-fillable syringe

110b, 110c housing

111 , 111a barrel

112, 112a stopper

113 distal end

114 septum

115 ferrule

116 hole

117 drug formulation

118a actuation plunger rod

118b delivery plunger rod

119, 119a proximal end

120 thumb pad

121 flange

123 Luer connection

123a screw fitting

124 septum needle

126 finger grip

126a thread

127 housing

128 delivery plunger rod

128a plunger rod

129a pad

131 finger flanges

135 gas-access pathway

136 passageway

140 transmission box

142 lock

144a actuation plunger rod b delivery plunger rod thumb pad amount distance needle main housing cartridge barrela syringe barrel b flange actuation plunger roda extension , 307a, 307b tolerance gap transmission housinga hole grip pin , 321d, 321e lever a axis , 323a travel stop c stop lock point , 333, 335 distance b stop , 403 advance mechanism distance position distance distance beam pivot position lever arrow actuation plunger rod arrow , 806 flange Axle center centerline , 833, 835 flat surface curved surface

Claims

1. A syringe system (1) for delivering a drug or medical formulation into the body of a patient, comprising a housing having a distal end (113) to which a hollow needle (200) may be attached, and an actuator provided for manual operation by a user, wherein said actuator is mechanically coupled to the interior of said needle (200) or said distal end (113) of said housing by a plunger system, said plunger system comprising an actuator plunger rod (118a, 144a, 306) and a delivery plunger rod (118b, 128, 144b) mechanically coupled to said actuator plunger rod (118a, 144a, 306) by a transmission system, wherein said transmission system converts a stroke of said actuator plunger rod (118a, 144a, 306) into a stroke of said delivery plunger rod (118b, 128, 144b) at a predetermined conversion ratio.

2. The syringe system (1) of claim 1 , wherein said transmission system comprises a conversion lever (321 , 451 , 801).

3. The syringe system (1) of claim 2, wherein said conversion lever (321 , 451 , 801) is mounted in said housing pivotable about an axis (321a, 452, 813) such that said actuator plunger rod (118a, 144a, 306), for driving rotation of said conversion lever (321 , 451 , 801) around said axis (321a, 452, 813), engages said conversion lever (321 , 451 , 801) at a driving offset with respect to that axis (321a, 452, 813), and said delivery plunger rod (118b, 128, 144b) is positioned for engagement by said conversion lever (321 , 451 , 801) at a receiving offset with respect to said axis (321a, 452, 813).

4. The syringe system (1) of claim 2 or 3, wherein said conversion lever (321 , 451 , 801) is profiled and has a number of flat surfaces (831 , 833, 835) and a number of curved surfaces (837), wherein, after completion of rotation of said conversion lever (321 , 451 , 801), a first of said flat surfaces (831) abuts a flange (805) of said actuation plunger.

5. The syringe system (1) of any one of claims 1 to 4, wherein said transmission system is designed for first having a priming stroke of said actuator plunger rod (118a, 144a, 306), before an actual ejecting stroke for ejection of said drug or medical formulation out of said distal end (113) is enabled.

6. The syringe system (1) of claim 5, wherein said housing comprises at least two housing components movable in relation to each other, and wherein said priming stroke is affected by moving two of said housing components relative to each other.

7. The syringe system (1) of claim 5 or 6, wherein ejection of said drug or medical formulation from within said hollow needle (200) or said distal end (113) by said delivery plunger rod (118b, 128, 144b) is blocked until after said priming stroke has been executed.

8. The syringe system (1) of any one of claims 1 to 7, further comprising an indicator system positioned at a proximal end of said housing.