Dead space flushing syringe

Abstract

To eliminate waste in a syringe for injection of a medical agent, a cylindrical syringe body (101) having in its most distal end a region of reduced inner diameter (105) is fitted with a plunger arrangement (110) attached to a plunger rod. The plunger arrangement is configured with a most proximal seal (112) and a most distal seal (111) connected to and spaced in axial direction by a plunger stem (113). A displacement agent is stored in the annulus around the plunger stem inside the syringe housing, between the most proximal and most distal seals. Medical agent (170) drawn into the syringe body on the distal side of most distal seal, may be expelled by moving plunger arrangement towards the distal end. Thereby, most distal seal folds and adapts to the region of reduced inner diameter and allows displacement agent to pass, flushing out medical agent in syringe dead space.

Description

[0001] Dead Space Flushing Syringe

[0002] Background

[0003] Vaccinations are known to be instrumental in fighting pandemics and diseases. Especially in low-income countries diseases eradicated decades ago in richer countries by means of vaccinations, are still very much existing and causing significant problems among the population. In many some areas of the world, the population also have to deal with diseases and ways of spreading, that is not an issue in other parts of the world. Historically, such issues have contributed to a high child mortality and reduced life expectancy, not to mention a reduced life quality for the population in such areas. Fortunately, the last few decades these health issues have been reduced significantly through vaccination efforts of a very large number of people in those regions.

[0004] Also, in the richer parts of the world, it has recently been proven that vaccinations are essential in fighting disease and ensure public health, not only regarding known diseases but also new viruses and pandemics. The Covid pandemic demonstrated that an effective vaccine can be developed in short time to mitigate the threat of a new virus, but to be effective it is required to perform vaccinations on a large scale. This requires vaccines to become available in very large quantities in very short time. Lack of availability slowed the vaccination efforts down during the beginning of the Covid pandemic and this resulted in more fatalities than would have been experienced, had availability not have been an issue.

[0005] Not only limitations in production capacity or faster rise in demand than ramp up in production can meet, can be the cause of limited availability. Costs may also be a limiting factor, especially in low-income countries. Unfortunately, the need for vaccinations is often higher in countries with the least funds to finance the required efforts.

[0006] Thus, it is in the interest of global public health, that an effective use of an available amount of vaccine is carried out, both in case the world supply of a vaccine is limited and insufficient and if limitations of means only allow for a limited amount of otherwise readily available vaccine to be acquired and distributed.

[0007] The first step in providing a more efficient use of any resource, is to reduce or eliminate the amount of waste of the given resource. Hence, methods of reducing the waste of vaccine substance would contribute to improve the ability to treat a larger part of the world population and faster, which will also make vaccines work more effectively. To reduce waste of vaccine, and drugs in general, the causes of waste must be identified. After production, drugs and vaccines have a limited lifespan and often require storage at less than ambient temperature. If stored for too long or at too high temperature, at some point, the vaccine or drug will have to be discarded and waste is introduced. The obvious solutions for this type of waste, is to spend the vaccine / drug in time and provide the required cooling during storage.

[0008] When administering a drug or vaccine, an amount of drug / vaccine is usually transferred from the vial the drug / vaccine is delivered in from the manufacturer to a syringe, from where it is to be injected into a recipient. The transfer of drug / vaccine from the vial into the syringe is usually done by penetrating a septum on the vial by a needle on the syringe and draw drug / vaccine into the syringe. However, there is a limit how much of the contents that can be extracted this way, depending on procedure used, design of the vial top, needle size and other parameters. This type of waste can be reduced by design of the vial top and the vial size. As the unextractable amount of drug / vaccine in a vial will be a relatively fixed amount with a given vial top, needle size and extraction procedure, the amount of waste can be reduced simply by providing a larger vial. However, the larger the vial is made, the larger is the risk that a vial will not be fully spend before having been stored in unseal (once septum is penetrated) and has to be discarded, where by amount of waste is increased.

[0009] The last cause of waste lies within the syringe. All syringes have a dead space. It is inherent in the principal of a syringe, in which a piston operates inside a cylinder. Any volume in front of the piston prior to filling will not be emptied when returning the piston to that same position during emptying. Thus, the scale of a syringe is not designed to show the contents of the syringe, but how much can be expected to come out of the syringe, when emptying it.

[0010] A standard 1ml syringe designed with a nozzle for attachment of a needle with a Luer-hub, have a dead space of approximately 0,1ml, which means that the syringe itself has a dead space of 10% of its full capacity. As the Luer-hub is based on the idea of a conical fitting, it has to be ensured that a void will always be present between the end of the syringe nozzle and the bottom of the conical hub. Otherwise, the conical sections will not engage and the needle will fall off. This contributes to the dead space of a syringe with detachable needle with a Luer-hub, such that it may be up to 0,15ml for 0,1ml syringe with needle attached.

[0011] Using such a standard syringe and needle to administer a dose of vaccine often in the range of 0,3ml-0,5ml, leads to a waste of between 30%-50%, meaning that for around every 2-3 doses administered, a full dose is wasted and discarded with the used syringes. This have led to the use of low dead space syringes, in which the dead space is reduced significantly, but as long as a standard Luer-connection is used to fit a needle, the dead space will not be lower than about 0,05ml, meaning the waste providing a 0,3ml dose will be about 17%, meaning that for every 6 doses, a full dose is wasted.

[0012] However, introducing the use of low dead space syringes, also introduce an added cost, as low dead space syringes are more expensive to manufacture. In situations where availability of a given drug / vaccine is limited, it makes sense to allow an increased cost of administration in order to reduce waste, to enable administration of a limited amount of vaccine / drug to as many recipients as possible. In other situations where funding is the limit, it may make sense to increase administration cost slightly too, to reduce waste and enable administration to more recipients, as the costs of syringe and needle are usually much lower than the cost of a dose. However, using special syringes and / or needles to reduce waste quickly surpass the cost of drug / vaccine, as it was seen some places in Europe during the Covid pandemic, where syringes costing more than 5 times the price of a dose were used for administration, to enable treatment of as many people as possible with the limited amount of vaccine available, regardless of costs.

[0013] More often, the situation is however a situation on which a limited budget needs provide treatment of as many as possible. In these situations, a reduced waste will enable treatment of more people, but if the cost of reducing the waste is smaller than the cost of the wasted drug / vaccine.

[0014] Thus, means of injection with less dead space or reduced cost compared to other means with similar dead space, would enable treatment of more people for the same means and thereby enable an improvement of global healthcare. It is an objective of the presented invention to provide a syringe that eliminates the issue of dead space, whereby waste in syringes can be eliminated at virtually no additional cost, and thus enable treatment of more people within an available budget.

[0015] Problem to be solved

[0016] As it is inherent in the working principal of a simple syringe, based on a piston with a given stroke inside a cylinder, that the volume inside the syringe in front of the piston at its end-of- travel position towards the outlet cannot be emptied, it follows that when a needle is attached, the volume of the void inside the given needle unit when fitted, will be added to the dead space. Although some needle units do not only attach on to the nozzle of a Luer-lock syringe, but also into the nozzle and thereby fill up some of the void inside the nozzle, there is a limit to how much these needle units can reduce the dead space of the combined injection system. This type of solution also only works with a very specific type of syringe, as the part going into the nozzle needs to go as far into the nozzle as possible, to reduce the dead space volume as much as possible, while at the same time must keep clear of the piston to prevent the needle unit from introducing a premature end-of-travel of the piston and thus introduce a large dead space within the syringe.

[0017] This solution has the drawback that it requires the use of a specific type of syringe (normally a standard syringe) and does not work with a low dead space syringe. This may complicate logistics. Furthermore, a needle hub to be fitted on a Luer-lock syringe is a cost-efficient solution because it is normally not very sensitive to tolerances, as the conical fitting works over a wide tolerance. If the inner diameter of the needle hub is a little on the low side, it will jam onto the nozzle near the nozzle tip and if the inner diameter of the hub is a bit on the large side, within the allowable tolerances, the hub will jam onto the nozzle near the nozzle base. However, a needle unit where a small tube fills the void of the nozzle, does not allow such wide tolerances. If allowed same tolerances as a standard needle unit hub, the small tube section going into the nozzle would have to be short enough to not collide with the piston at its lowest position, even if the needle hub onto is jammed onto the nozzle near its base. This would mean the small tube section only went in very little into the nozzle and reduced the dead space very little, when the hub inner diameter was on the low side of the tolerances and jammed onto the nozzle near the nozzle tip. This means that much smaller tolerances of the conical part of the needle hub is acceptable. As the small tube going into the nozzle of the syringe to reduce the volume also needs to seal the void between the nozzle tip and the bottom of the inner coneshape of the needle hub off, the tube section needs to fit so well inside the nozzle, that practically no annulus is left between the tube and the nozzle, while still making sure the tube is small enough to enter the nozzle. As the manufacturer of the needle units can only adjust the allowable tolerances on the needle units, the allowable tolerances are further reduced, as the existing tolerances of the nozzle will have to be taken into account as well.

[0018] Increasing production accuracy and narrowing the allowable tolerances of the product increases production costs significantly, in most cases well exceeding the cost of the drug / vaccine otherwise wasted. This applies to other known solutions of special connectors, wherein a special syringe is fitted with a connector for a specific needle unit to provide a combined solution with virtually no dead space. They are complicated and based on very small allowable tolerances, which makes production expensive, whereby the added cost will on most cases outweigh the benefits of reducing waste.

[0019] Low dead space syringes wherein a small tab on the piston is designed to fill most of the volume in the nozzle also suffer from increased costs of production due to required tolerances, although the extra cost is normally kept low by allowing some clearance between the tab and inner wall of the nozzle, where by the dead space is reduced a little less.

[0020] Thus, the problem to be solved, is to reduce the dead space of a syringe with needle, without introducing the need for more narrow production tolerances than applicable for a standard syringe to achieve said reduction of dead space.

[0021] It is a further objective to provide a solution that does not require stricter than standard production tolerances and does not require additional parts, compared to a standard syringe, whereby increase in production cost should be negligible, if relevant at all.

[0022] Brief description of claimed Invention

[0023] The claimed invention comprises a cylindrical syringe housing with an end wall with an opening or transitioning into a neck with an opening, wherein a section of the cylindrical housing has a reduced diameter. Said section of reduced diameter may be an axially displaceable insert inside a cylindrical syringe housing of uniform inner diameter or be a fixed insert or integral part of the cylindrical syringe housing having a reduced inner diameter in a section at its distal end. A single plunger with two axially separated seals is slidably arranged inside the cylindrical housing and operable in axial direction of the cylindrical housing by means of a plunger rod. The plunger has a substantially smaller diameter than the inner diameter of the section of larger inner diameter of the cylindrical syringe housing and only slightly smaller than the inner diameter of the section of the cylindrical of reduced inner diameter. A volume of gas (eg. Sterile air) is trapped in the annulus between the stem of the plunger and the larger inner diameter of the cylindrical syringe body, between the two axially separated seals of the plunger, a proximal seal nearest the plunger rod and a distal seal furthest from the plunger rod. By manipulation of said plunger, the volume inside the cylindrical syringe housing in the distal end of the plunger, between the end wall of the syringe housing and the distal plunger seal, including the dead space in the neck and needle or tube, fitted to said neck, can be filled with a liquid active substance. Once filled, the contents can be discharged from the syringe by moving the plunger towards the distal end of the syringe housing by applying force on the plunger rod. The plunger with air trapped between its two seals displaces the volume of active substance on the distal side of the distal plunger seal, until the distal seal reaches the section of reduced inner diameter. The distal seal then deforms and enters the reduced inner diameter of the syringe housing, whereby the sealing between the air-filled annulus between plunger stem and syringe housing is compromised and air is allowed to escape pass the compromised distal seal. As the plunger is moved further towards the distal end of the cylindrical syringe housing, the air inside said annulus is displaced by the reducing diameter of syringe housing, whereby the air starts to displace the volume on the distal side of the distal seal, until the volume of active substance is displaced completely from the volume on the distal side of the distal seal, including the dead space of the neck and an attached needle or tube. (Claim 1)

[0024] Prior art

[0025] Closest prior art is US Patent No. US 10,639,429 B2 disclosing different embodiments of a syringe comprising a cylindrical syringe body having a limiting wall, which transitions into a neck in its distal end, wherein two mechanically connected plungers are axially displaceable, actuated by a plunger rod forming part of the proximal plunger. A flushing medium (e.g. Sterile air, a saline solution or other suitable fluid or gas) is contained between the two plungers, and the active medium to be injected is contained in the volume of the syringe housing in front of the distal plunger. The plungers are mechanically connected to maintain an essentially fixed distance between the plungers, until the distal plunger collides with the end wall of the syringe housing and the medium to be injected has been expelled, except for the volume in the dead space of the syringe and attached needle or catheter tube. When further applying pressure on the plunger rod, forming part of the proximal plunger, the structure connecting the two plungers collapse or deform, thus allowing the proximal plunger to move towards the now stationary distal plunger and reduce the distance between the two plungers inside the syringe housing, whereby the volume between the two plungers is reduced. The medium housed between the two plungers escapes the through slit or valved openings in the distal plunger and flush out remaining active medium in the dead space of the syringe and needle or catheter tube.

[0026] It is from the description obvious that the invention claimed in US 10,639,429 B2 is primarily intended for relatively large syringes, as it is described as a solution that makes it safer and easier in use for injections through a catheter or a butterfly cannula. Furthermore, it is noted in the description that the volume between the plunger should be limited to less than 0,5ml, to rule out the risk of an air embolism when air is used as the flushing medium, which suggest use for intravenous injection and an expected size of dead space about 10 times as large as for the types of syringes normally used for vaccinations. Some of the embodiments shown also indicate a relatively syringe (compared to syringes used for vaccinations), as the required features will be both challenging and expensive to manufacture.

[0027] In particular the embodiment illustrated in figs. 12-14 bears some resemblance to the invention disclosed in this application. However, the embodiment as it is described have some obvious deficiencies, that will not only make it very challenging to scale down, but also make it virtually impossible to realize. The embodiment shown and the description disclose a bellow forming a proximal plunger and a distal plunger, where both the plungers and the stem between them are hollow, to allow the bellow to collapse when the distal plunger meets the end of travel in the syringe housing and thus allow the proximal plunger to move towards the distal plunger. The air housed in the annulus between the bellow and the syringe housing is then to pass the distal plunger though small openings along the edge of the distal plunger, which consequently mean that the distal plunger is not sealing completely between the active medium in front of the distal plunger and the air-filled annulus. This may work, if the openings are small enough to ensure the surface tension of the fluid in the distal end of the syringe prevents the fluid from entering the air-filled annulus through the small openings. However, this will also limit the flow of air though the very small openings and require a significant force to be applied on the plunger rod to provide sufficient air pressure to overcome the flow resistance of the small holes, which will lead to a high airspeed and turbulent flow, forming bubbles and not push the active medium fluid in front of the air. Furthermore, for the air to be able to push the fluid between the syringe end wall and the distal plunger towards the centered outlet, recesses in the face of the distal plunger are described being connected to the small holes along the sealing edge. These recesses themselves increase the dead space of the syringe. This all means that the bellow needs to have very different properties during the different stages of the injection sequence. While drawing the active fluid and during injection of the active fluid, the bellow must act like a solid element with little deformation and elasticity. If axial forces are not transmitted with very little deformation of the bellow, the air inside the bellow and outside the bellow will work as a spring when drawing the active fluid into the syringe and bleeding the syringe of air, making it very difficult to draw a correct dose. If the axial force applied on the plunger rod is not primarily transmitted though the bellow stem, the bellow will be compressed and the air pressure increase, which may lead to air being pushed out of the openings along the distal plunger seal and cause bubbles in the active fluid and thus introduce a risk of blood emboli. To further add to the problem, the description suggests the air inside the bellow able to escape through an opening in the plunger rod or the proximal plunger. This means that the air inside the bellow will not aid in providing stability and rigidity to the bellow unit and thus only the material properties of the bellow can be relied on the prevent air to be released prematurely and cause bubbles in the active fluid. This contradicts the requirement of an elastically compressible bellow (Column 10, L26-27), that will easily collapse and deform, once the distal plunger reach its end-of-travel at the syringe wall.

[0028] Although the invention disclosed in this application relies on the same basic principle of using sterile air or a sterile saline solution to flush the dead space of the syringe and an attached cannula of remains of the active medium to be injected and said sterile air or saline solution is stored in an annulus between a plunger stem and the syringe housing, as disclosed in prior art, novelty and inventive step over prior art is claimed due to the following features of the presented invention. a) The claimed invention relates to a syringe with only one plunger and not two mechanically connected plungers. Although the solution in the herein disclosed invention relates to a plunger with a proximal and a distal seal against the syringe housing, it cannot be considered as two plungers, as the proximal seal cannot move relative to the distal seal, which is the subject matter of the invention disclosed in US 10,639,429 B2. b) US 10,639,429 B2 does not mention or provide any teachings about an insert or feature integrated in the syringe housing designed to displace the majority of the volume of flushing gas or fluid contained in an annulus between two seals on a single plunger. c) US 10,639,429 B2 does not mention or provide any teachings about how to allow air contained in the annulus between two sealed surfaces to escape, as the solution described in US 10,639,429 B2 is based on the distal plunger only being partially sealed. d) US 10,639,429 B2 does not mention or provide any teachings about how to allow air contained in the annulus between two sealed surfaces to escape prior to the distal seal reaching its end-of-travel.

[0029] The invention disclosed in US 10,639,429 B2 is essentially based on the principal of two plungers moving with a fixed distance between them, in parallel inside a cylinder with a fixed diameter, until the distal plunger meets its end of travel and thus stops moving. The proximal plunger then starts moving relative to the distal plunger, whereby a flushing gas or liquid is displaced from the cavity between the distal and the proximal plungers. Hence, the invention disclosed in US 10,639,429 B2 is a syringe in which two temporarily interconnected plungers displace the content of two cavities sequentially by linear movement. First the cavity, consisting of cylindrical housing with an end wall in one end and the distal plunger in the opposing end, containing a drug or active substance is displaced by the distal plunger. Once the volume of said first cavity is displaced by the distal plunger, the volume of the second cavity, consisting of a cylindrical housing ended by the distal plunger in one end and the proximal plunger in the opposing end, is displaced by a linear movement of the proximal plunger.

[0030] In the hereby presented invention, a single plunger with two seals also limits two cavities inside a cylindrical housing, where the first cavity containing the active substance is limited by a cylindrical housing with an end wall in one end and the distal seal in the opposite end. A second volume containing a flushing gas or liquid is also defined by a cylindrical housing with the distal seal in one end and the proximal seal in the opposing end, but as the distal and proximal seals can never move relative to each other in axial direction, it is a single plunger and not two temporarily connected plungers. Thus, the volume of the second cavity is not displaced by linear movement of the proximal seal towards the distal seal, but essentially by a reduction of the cylindrical housing diameter. Thus, the displacement sequence is different. The volume of the first volume containing the active substance is displaced by a linear motion of a plunger in both the hereby disclosed invention and in the invention disclosed in US 10,639,429 B2. But where the volume of the second cavity is displaced by yet a linear motion of a second plunger in the invention disclosed in US 10,639,429 B2, the volume contained in the second cavity in the hereby disclosed invention, is displaced by a reduction of the diameter of the cylindrical housing, essentially being a radial movement of the cylindrical housing wall towards the axial center of the cylinder. The sequence is however not only different in the way the second volume is displaced, but also in timing. Where the displacement of the contents of second volume is initiated prior to the finalization of the displacement of the first volume in the hereby disclosed invention, the displacement of the second volume is only initiated after the displacement of the first volume is ended in the invention disclosed in US 10,639,429 B2, which is also clearly stated in both claims and description of US 10,639,429 B2. Prior art also includes the invention disclosed in KR20230000266A describing a syringe for injection of an active substance (pars. 0033-0042; fig. 3-5 comprising:

[0031] -a cylindrical syringe body - a cylindrical syringe body (barrel 2100) with a limiting wall (connection part 2130) that is transitioning into a neck of reduced inner diameter (discharge pipe 2120),

[0032] - an axially displaceable plunger arrangement (packing 2300) with means of actuation (plunger 2200) and two sealing members (first contact portion 2310, first header 2340) spaced apart in axial direction by a plunger stem (first protrusion 2330), and the first contact portion provides a circumferential seal against the cylindrical syringe body.

[0033] Wherein:

[0034] - the region of reduced inner diameter is located in distal direction of the most proximal sealing member (fig. 4)

[0035] - the plunger arrangement is configured for engagement with the region of reduced inner diameter (pars. 0039-0041) and the region of reduced inner diameter is provided with means to deform the most distal sealing member (diameter of first header is larger than the inner diameter of the discharge pipe, par. 0041) such that the plunger arrangement is adapted to partly slide into the region of reduced inner diameter (par. 0042; fig. 5)

[0036] - the syringe is adapted for drawing a fluid active substance into the cylindrical syringe body through the neck by manipulation of the plunger arrangement (par. 0002), and to be accommodated inside the cylindrical syringe body (par. 0034).

[0037] However, the invention does not disclose a solution where the most distal sealing member provides a circumferential seal against the cylindrical syringe body and the sealing members provide a sealed volume in an annulus between the plunger arrangement and the cylindrical syringe body.

[0038] The invention disclosed in KR20230000266A is essentially what is commonly known as a low dead space syringe, which is a syringe with a protrusion on its plunger to displace most but not all fluid in the neck of the syringe body. In most low dead space syringes, the neck is slightly coned both on the outside, to allow fitting of a Luer-lock needle unit, and on the inside to provide a slip-angle during molding. The protrusion is typically coned too, but at a larger angle, to allow for production tolerances and ensure the protrusion will enter the neck, as well as allow fluid from the volume in the cylindrical syringe housing to pass. Often a small indentation is made in the protrusion, to allow tighter fit in the annulus between the neck and the protrusion, leaving a smaller dead space. The novel feature of the invention disclosed in KR20230000266A is a sealing lip in the tip of the said protrusion, claimed to be aiding in emptying the neck of fluid during injection, and further acting as a lock preventing reuse of the syringe once emptied. In this configuration the dead space of the syringe itself is minimized, but the dead space of the needle hub remains unemptied. In a second embodiment, a second protrusion (2350) adapted for engagement with the needle hub further reduce the dead space of the injection system comprising a syringe with an attached needle unit. However, such a solution requires very small production tolerances increasing costs significantly and still leaves a small dead space. The invention does not disclose or provide any teaching relevant to the concept of providing a syringe with a sealed volume of gas / fluid prior to use, using said gas / fluid in a sealed annulus to flush remaining active substance out of the dead space in syringe and needle unit.

[0039] Detailed description

[0040] The claimed invention comprises a cylindrical syringe housing with an open proximal end and a limiting wall at its distal end. Said limiting wall may have an opening or transition into a neck, suitable for delivering an active substance through. Within said cylindrical housing, as section of reduced inner diameter is established either as an integral part of the cylindrical syringe housing, such that the inner diameter is reduced at the distal end of the housing, or as an inserted separate component able to move in axial direction inside a cylindrical housing with a uniform inner diameter along its entire length.

[0041] A plunger is slidably arranged inside the cylindrical syringe housing and provided with means for manipulating the axial position of the plunger inside the cylindrical syringe housing, secured in the proximal end of the plunger. Said means for manipulation could be a simple plunger rod. The plunger is characterized in having a primary seal in its most proximal end and a secondary seal or separator in the distal direction of the primary seal. Thus, the primary seal and the secondary seal are separated in axial direction by a connecting member or stem, such that the plunger inside the cylindrical syringe housing defines a closed volume as an annulus around the connecting member or stem inside the cylindrical syringe housing, between the two seals. Said closed volume may be filed with atmospheric air, an inert gas or a saline solution or other fluid, any of which may be sterilized. Said air, gas or saline solution will in general be referred to as the "displacement agent". The plunger limiting a closed volume inside the cylindrical syringe housing may be manipulated in axial direction inside the cylindrical syringe housing and will, as longs as it is operated within the section of the main diameter of the syringe housing, act as a solid plunger. By manipulation of the axial position of the plunger within the syringe housing, a volume inside the syringe housing between the plunger and the limiting wall at the distal end of the syringe housing can be varied in size. This volume constitutes the working volume of the syringe.

[0042] When the plunger is operated in the section of main inner diameter of the syringe housing, the plunger acts like a solid plunger and the working volume inside the syringe housing in distal direction of the plunger varies with the axial displacement, such that the change of volume in front (distal direction) of the plunger from a given length of axial plunger movement equals the length of movement time the cross-section area of the main inner diameter of the syringe housing.

[0043] However, when the plunger is moved in distal direction to a position in which the secondary seal (most distal seal) of the plunger enters the section of reduced inner diameter of the syringe housing, being the transition zone between main inner diameter and fully reduced inner diameter, the secondary seal is compromised and the working volume now consist of the volume inside the syringe housing on the distal side of the most proximal primary seal of the plunger and not the most distal secondary seal of the plunger.

[0044] The reduced inner diameter of the syringe housing is designed to be able to compromise and fold the most distal (secondary) seal and accommodate both the folded secondary seal and the stem of the plunger, such that a volume corresponding to the sum of the dead space volume of the syringe neck and the expected dead space volume of an attached needle hub and needle is displaced from the annulus around the stem of the plunger. Thereby, the air stored between the primary and secondary seals of the plunger inside the main diameter of the syringe housing is used as a secondary work media to displace the fluid active substance, that would otherwise be left in the dead space of the syringe and attached needle and needle hub.

[0045] Using the invented syringe, requires the plunger to be placed adjacent to the section of the section of reduced inner diameter in proximal direction and the opening or neck in the limiting wall at the distal end of the syringe housing hydraulically connected to a reservoir of an active fluid substance. This may be provided by attaching a needle with a needle hub to a neck protruding from the limiting wall, and insert said needle in a vial containing said active fluid substance. Once the volume limited by the syringe housing and the plunger is hydraulically connected to a fluid active substance, the plunger can be moved by the means of manipulation (e.g. Plunger rod) in proximal direction inside the syringe housing, whereby the active fluid substance will be sucked into the syringe housing, into the volume inside the syringe housing in front of the plunger. This procedure of filling a fluid active substance into the syringe is almost identical to the procedure of filling a standard syringe. However, when filling a standard syringe, the plunger is normally pushed to its most distal position to limit the volume of air between the plunger and the reservoir of fluid active substance. This is not allowable using the invented syringe, as the secondary and most distal seal, is not allowed to enter the section of reduced inner diameter of the syringe housing during, or prior to, the filling of the syringe, as this would enable fluid active substance to enter the volume between the seals of the plunger. Means to prevent such an error of operation is not disclosed in this invention. However, different means for preventing use of a syringe having been operated wrongly in this manner during preparation and filling, will be presented.

[0046] The lack of option to minimize the volume between the fluid reservoir (vial) and the plunger, as in a standard syringe, means that a substantially larger amount of air will be sucked into the syringe housing during the initial stage of filling the syringe. This means that a larger amount of air has to be bled out prior to injection, compared to when using a standard syringe. As means of preventing use of a syringe having been operated wrongly during preparation and filling will also impact the possibilities of bleeding out air in the syringe, an appropriate procedure will be described in details, even though very similar to how a standard syringe is filled and prepared with a given size of dose.

[0047] When a syringe has been prepared and adjusted to provide a given size of dose, the needle is inserted in the recipient of the fluid active substance. The administrator of the injection can then activate the means of manipulation of the plunger position withing the syringe house and apply pressure on the plunger. The plunger will then start moving in distal direction, whereby fluid active substance will be expelled from the volume inside the syringe housing, in front (distal side) of the plunger, with a rate (volume / second of the plunger velocity times the crosssection area of the main inner diameter of the syringe house, until the most distal seal of the plunger reach the transition zone inside the syringe housing and the inner diameter of the syringe housing begin to decrease.

[0048] As the secondary seal enter the transition zone, in which the inner diameter of the syringe housing is reduced, the rate of injection initially drops as the cross-section area of fluid being pushed in front (distal side) of the secondary seal is getting smaller and smaller and the seal is deformed, while air between the most distal seal and the most proximate seal is being compressed slightly, until the most distal (secondary) seal starts to fold and sealing is compromised. The volume of the reduced inner diameter of the syringe housing now enters the annulus between the most proximate and the most distal seal of the plunger, displacing some of the volume in which air, gas or saline solution was until then stored, where by pressure in the volume between the most proximal seal and the most distal seal of the plunger increases significantly. The increase pressure causes the air, gas or saline solution to exit pass the most distal (secondary) seal through the folds in the seal and displace fluid active substance on the distal side of the most distal (secondary) seal of the plunger.

[0049] The rate of which fluid active substance is expelled now increases, as the most proximal seal still displaces a volume equal to the length of axial displacement pr. time unit times the crosssection area of the larger inner diameter, while the reduced inner diameter further displaces a volume equal to the length of axial displacement pr. time unit times the cross-section area of the diameter reduction. This means that the surface of the fluid active substance, or the boundary between the fluid active substance and the displacing agent stored between the most proximal seal and the most distal seal of the plunger, starts to move faster in distal direction than the plunger is moved in distal direction. Thus, the active fluid substance is displaced and pushed all the way out through the dead space of the syringe, the needle hub and the needle, before the plunger reach its most distal position, limited by either the most proximal seal connecting with the reduction of inner diameter of the syringe housing, or when most distal seal connects with the limiting wall of syringe housing.

[0050] In the following, the above-described invention and exemplary embodiments utilizing the described principals, are described in more details, referring to illustrations of said embodiments. The detailed descriptions and illustrations relate to different configurations and additional features of the components not described in the above, but nevertheless be based on the principals and characterizing features of the disclosed invention. The provided illustrations of embodiments shall be seen as exemplary and may not include all comprehensible combinations of feature and should not be considered a limitation of the scope and extend of the claimed invention,.

[0051] It should also be noted, that the secondary / most distal seal of the plunger is sometimes also referred to as a separator. This is to imply, that the purpose of this feature is to provide a temporary separation between the displacement agent and the fluid active substance, while operating the plunger in the main, or large inner diameter of the syringe housing, but able to adapt to the reduced inner diameter of the syringe housing, where it may allow displacing agent to pass. Thus, the secondary seal / separator my not actually seal, but be designed with a clearance small enough for the surface tension of the fluid active substance to prevent the fluid active substance to pass through said clearance. The primary seal is consistently referred to as a seal, since this is required for various reasons to be an airtight seal with no clearance.

[0052] List of Drawings

[0053] Fig. 1: Exploded view of simple embodiment according to invention.

[0054] Fig. 2: Section view of simple embodiment "as delivered".

[0055] Fig. 3: Section view of simple embodiment prior to filling.

[0056] Fig. 4: Section view of simple embodiment during filling.

[0057] Fig. 5: Section view of simple embodiment after bleeding.

[0058] Fig. 6: Section view of simple embodiment inserted in skin.

[0059] Fig. 7: Section view of simple embodiment during injection step 1.

[0060] Fig. 8: Section view of simple embodiment during injection step 2

[0061] Fig. 9: Section view of simple embodiment during injection step 3.

[0062] Fig. 10: Section view of simple embodiment during injection step 4.

[0063] Fig. 11: Section view of simple embodiment during injection step 5.

[0064] Fig. 12: Section view of simple embodiment during injection step 6.

[0065] Fig. 13: Section view of simple embodiment during injection step 7.

[0066] Fig. 14: Section view of simple embodiment at end-of-dose.

[0067] Figs. 15a-f: Section views of different embodiments of plunger arrangement.

[0068] Fig. 16a-b: Section views of different configurations of the region of reduced inner diameter.

[0069] Fig. 17a-b: Section views of region of reduced inner diameter with one or more flow channels.

[0070] Fig. 18a-d: Section views of different embodiments of fixed diameter reducing inserts. Fig. 19a-d: Section views of first embodiment providing the feature of auto-disabling the syringe after first use, shown in different stages during injection.

[0071] Fig. 20a-b: Section views of second embodiment providing the feature of auto-disabling the syringe after first use, shown in different stages during injection.

[0072] Fig. 21a-c: Section views of embodiment with a floating diameter reducing insert.

[0073] Description of Drawings

[0074] In Fig. 1, the simplest embodiment of a syringe (100) according to the invention is shown in an exploded view, showing the details of each of the required components. A cylindrical syringe body (101) is provided with a limiting wall (102) in the distal end of the syringe body. The limiting wall (102) is in this particular embodiment transitioning into a neck (103), on which an injection needle (not shown) can be fitted, having an opening (104) suitable for the active substance to be delivered through. The cylindrical body (101) has a main inner diameter (106) from the most proximal end of the syringe housing (101) towards the distal end of the syringe housing, where a region of reduced inner diameter (105) follows a region of transition (107) from the main diameter (106) into the reduced inner diameter (105) of the syringe housing. The syringe housing (101) is provided with means of indication of dose size (108), in this embodiment being a simple marking of where the plunger needs to be aligned after filling and bleeding the syringe, in order for a specific dose size to be expelled. The syringe housing (101) may also be provided with means of handling (109). A plunger arrangement (110) is fig. 1 shown as a single plunger component having a distal sealing member (111) and a proximal sealing member (112), separated in axial direction by a plunger stem (113). The plunger (110) is provided with means (114) for attachment of a plunger rod (120) for actuation of the plunger (110) in axial direction. The plunger rod (120) is in this embodiment fitted with means of attachment (121) to the plunger (110). However, the plunger (110) and the means of actuation (120) may be combined and formed by a single component.

[0075] During manufacture, the Plunger arrangement (110) is attached to the plunger rod (120) and inserted into the syringe housing (101) and sterilized. During this assembly, air (130) will be trapped in a sealed volume inside the syringe housing (101) between the most distal seal (111) and the most proximal seal (112) of the plunger arrangement (110) as shown in fig. 2. Sterilization could be done using radiation, which would also sterilize the trapped air (130) inside the syringe housing (101). Provisions for allowing other means of sterilization or filling the enclosed volume (130) with an inert gas or a liquid e.g. a saline solution could be introduced in the syringe housing. The assembled syringe may then be stored until use with the most distal seal (111) near or adjacent to the transition zone (107) at the proximal end of the section of reduced inner diameter (105) inside the syringe housing (101).

[0076] When the syringe is taken into use, a needle unit (300) is fitted on the neck (103) of the syringe housing (101). The needle unit (300) consists of a needle hub (380) with an injection needle or cannula (381). The needle unit (300) is shown in dashed lines in fig. 3, as it is not a part of the invention disclosed. However, the needle unit (300) introduces a dead space, that adds to the dead space of a syringe / needle assembly and with some syringes adds a dead space far larger than the dead space of the syringe itself. As it is the objective of the presented invention to compensate for the dead space of both syringe and needle unit, it is necessary to include the presence of a needle unit in the descriptions and illustrations of the working principal of the presented invention, although the needle unit is not a part of the embodiment of the invention as such, but related to the subject matter of the invention.

[0077] The most common fitting of needle units on syringes, is the Luer-coupling based on a coned syringe neck fitting into a coned opening of a needle hub. This principal requires the two coned surfaces to connect and allow the neck of the syringe to jam in the opening of the needle hub, to fix the needle unit on the syringe neck. This again requires some distance between the end of the syringe neck (103) and the bottom of the opening of the needle hub (180) to remain when the coned neck jams in the coned opening of the needle hub, as the coned fitting would not be able to jam, if the tip of the syringe neck connected with the bottom of the cone-shaped opening prior to the coned surfaces jamming. The Luer-connection standard specifies allowable tolerances of diameter and cone angle of both needle hub hole and syringe neck, and as even the largest allowable neck tip diameter has to be able to engage with the smallest allowable needle hub opening diameter, there is a limit to how small the distance between the bottom of the needle hub opening and the syringe neck tip can be designed and thus, a limit to how small the dead space volume in the needle hub (382) can be designed to be, when the needle unit is attached to the neck of a syringe. Other types of connection systems exists and some are specifically designed to minimize the dead space volume introduced, but it cannot be completely eliminated when taking production tolerances into account and hence very narrow production tolerances are required to minimize dead space, which significantly increase the production costs of syringe and needle unit. In the syringe (200) prepared with a needle unit (300) prior to filling shown in fig. 3, a volume (160) of atmospheric air inside the syringe housing (101) continues out through the neck (103) and into the added dead space volume (382) of the needle hub. Furthermore, a small dead space volume inside the cannula (381) itself is added as well.

[0078] The syringe (200) fitted with a needle unit (300) in fig. 3, is inserted through a vial septum, into a vial (not shown) containing a medicinal agent for injection. This is performed in an essentially vertical position with the needle (distal) end up, which is common practice when drawing a dose into a syringe. The plunger rod (120) and thus the plunger arrangement (110) is then pulled in proximal direction and medicinal agent is drawn through the cannula (381) and needle hub (380) into the syringe, as the volume (160) on the distal side of the most distal seal (111) expands. The plunger arrangement (110) is moved to a position significantly beyond the dose size indicator (108) in proximal direction. A volume of sterilized air (130) or other displacement agent is stored in the annulus around the stem (113) of the plunger arrangement inside the syringe housing (101), between the most distal sealing member (111) and the most proximal sealing member (112) of the plunger arrangement (110).

[0079] In fig. 4 the plunger arrangement (110) has been moved to a position in proximal direction of the dose size indicator (108) on the syringe housing (101) and a volume of medicinal agent (170) had been transferred into the syringe housing (101). As the syringe housing (101) and needle unit (300) contained air in the needle hub (382), the neck of the syringe (103) and inside the syringe housing (160) prior to drawing the volume of medicinal agent (170) into the syringe housing (101), the same volume of air is still present in the syringe. By tapping the syringe housing (101) with a finger, the air moves to the upper part of the volume, which in fig. 4 is in distal direction. Thus, the syringe now contains a volume of medicinal agent (170) on the distal side of the most distal sealing member (111) of the plunger arrangement and a volume of air (160) on top (distal) of the medicinal agent, inside the syringe and needle unit. The cannula tip is still kept inside the vial (not shown). The air (160) is bled out of the syringe and needle by pushing the plunger arrangement (110) towards the distal end inside the syringe housing (101), whereby the air will exit the syringe housing (101) and the needle unit (300) through the cannula (381) into the vial (not shown) containing the medicinal agent.

[0080] The motion in distal direction of the plunger arrangement (110) inside the syringe housing (101) is continued in order to expel excess medicinal agent inside the syringe into the vial (not shown) containing the medicinal agent, until the most distal sealing member (111) of the plunger arrangement (110) reach the dose size indicator (108) on the syringe housing (101) as shown in fig. 5. The syringe is now prepared for injection of a dose of the medicinal agent, of a size corresponding to the dose size indicator (108) and the cannula (381) can be extracted from the vial (not shown) containing the medicinal agent. The entire volume inside the syringe housing (101) and neck (103), as well as the volume (382) inside the needle hub (380) and cannula (381) in front of the most distal sealing member (111) of the plunger arrangement

[0081] (110) is now filled with medicinal agent (170) without any air. The volume inside the syringe housing (101) surrounding the plunger stem (113) between the most distal sealing member

[0082] (111) and the most proximal sealing member (112) is still filled with sterilized air (130). The syringe is now prepared for injection of a dose corresponding to the size indicated by the dose size indicator (108).

[0083] In fig. 6, the cannula (381) of the needle unit (300) is inserted through the skin (698) and into a muscle (699) of a dose recipient (600). The most distal sealing member (111) of the plunger arrangement (110) is aligned with the dose size indicator (108). Injection is started by pushing the plunger rod (120) towards the distal end of the syringe housing (101), where by medicinal agent (170) in the volume inside the syringe housing (101) at the distal side of the most distal sealing member (111) of the plunger arrangement (110) is injected, as shown in figs. 7 and 7a. As the most distal sealing member (111) reach the transition zone (107), the sealing most distal member (107) starts to deform, as the tip of the stem (113) of the plunger arrangement continues into the region of reducing diameter (107), as illustrated in figs. 8 and 8a.

[0084] The outer diameter of the most distal sealing member (111) has to decrease and fold back towards the proximal end of the plunger arrangement (110), and the most distal sealing member (111) starts to fold (880), as illustrated in fig 8a. During the initial stage of the deformation of the most distal sealing member (111), the sterile air in the annulus on the proximal side of the most distal sealing member (111) is compressed a little and air pressure increases. The most distal sealing member (111) then continues to fold, as the diameter decreases further, which compromises sealing. However, due to the increased air pressure, in the annulus (130), the medicinal agent (170) does not enter the annulus, as the pressure of the medicinal agent (170) does not increase, since the medicinal agent (170) can still flow out through the syringe neck (103) and the needle unit (300) and into the recipient of the dose (600).

[0085] The air inside the annulus (130) is further compressed as the plunger arrangement is moved further inside the region of reduced diameter (105), as shown in figs. 9 and 9a, due to the volume of air now being displaced by the increased thickness of the syringe wall (105), while the most distal sealing member (111) continues to deform and fold. At some point the folds on the most distal seal (111) provides sufficiently large leaks for the compressed air in the annulus (130) to pass through the openings (980) in the folds of the most distal sealing member (111) as shown in fig. 9a.

[0086] As the air from the annulus (130) expands through the openings (980) in the folds of the most distal sealing member (111), it displaces some of the medicinal agent (170). If the syringe is placed with its axis tilted less than about 60° from vertical and its proximal end up, the air from the annulus will stay above the fluid medicinal agent (170). The surface tension of the medicinal agent will in small diameter syringes prevent the formation of bubbles. Instead, the air (130) passing (131) through the openings (980) in the most distal sealing member (111) will stay behind (in proximal direction) of the medicinal agent (in distal direction) and cause the liquid surface (171) of the medicinal agent to move in distal direction away from the most distal sealing member (111), as shown in figs. 10 and 10a.

[0087] Air flows (131) through the openings (980) in the folds of the most distal sealing member (111) from the annulus (130) on the proximal side of the most distal sealing member (111) to the distal side of the most distal sealing member, displacing a volume (981) of medicinal agent (170) between the plunger arrangement (110) and the medicinal agent (170).

[0088] As the volume of sterilized air (130) being displaced by the reduced diameter (105) by a given movement of the plunger arrangement (110) is flowing from the proximal side of the most distal sealing member (111) to the distal side of the most distal sealing member (111), the volume of sterilized air (981) between the most distal sealing member (111) of the plunger arrangement (110) and the surface (171) the volume of medicinal agent (170) increases, as the plunger arrangement (110) moves towards the distal end of the syringe housing (101), as illustrated in fig. 11 and 11a. Thus, the distance between the plunger arrangement (110) and the surface (171) of the medicinal agent (170) increases as the plunger arrangement (110) continues moving in distal direction inside the syringe housing (101). For a given distance Dpof movement of the plunger arrangement, the surface (171) of the medicinal agent (170) will move a distance of DSI=DR+ADI. AS the surface (171) of the medicinal agent (171) goes into the further reduced diameter of the neck (103) of the syringe housing (101), as shown in figs. 12 and 12a, the difference in rate of movement will increase, such that the surface (171) of the medicinal agent (170) will then move a distance of DS2=DR+AD2, where AD2 > ADi, when the plunger arrangement is moved a distance of DR. Thereby, the medicinal agent (170) is emptied out of the syringe housing (101) and the syringe neck (103) and only a small amount of medicinal agent (170) remains in the volume (382) inside the needle hub (380) even before the plunger arrangement (110) reaches its end of travel, as illustrated in figs. 13 and 13a.

[0089] When the plunger arrangement (110) reaches its end of travel as illustrated in fig. 14, the volume of air (130) contained in the annulus around the stem (113) has been reduced, as the region of reduced diameter (105) displaced a large part of the volume filled with air prior to injection. The volume of air displaced from the annulus has now displaced all of the medicinal agent, not only emptying the dead space in the syringe neck (103) of the syringe itself, but also in the dead space of the needle hub (380) and the cannula (381), leaving no wasted medicinal agent in the syringe or needle. As a surplus of displacement agent, here sterile air, may also be injected into the recipient, air or inert gas should only be used for intramuscular injections, to avoid the risk of blood embolies. A liquid displacement agent may be used instead of the sterile air (130) described in the above description, for use with intravenous injections.

[0090] Figures 1-14 shows a very simple embodiment, illustrating the subject matter and working principals of the disclosed invention. However, different features may be added and used in different configurations, to improve performance, functionality, safety and usability. In the following different added features will be presented and described as exemplary alternatives of embodiments. The description of added features and their embodiments, as well as the configurations described and illustrated should not be considered a complete list of options thought feasible. The added features and functionalities are considered obvious to the skilled person to introduce, once becoming familiar with the subject matter of the herein disclosed invention.

[0091] It should be obvious to the skilled person, that the three main aspects of realizing the effect of the subject matter of the invention, are:

[0092] - to prevent the plunger arrangement stem (113) from bending out and collapsing, which would both compromise the separation between displacement agent (130) and medicinal agent (170) prematurely, as well as jam the plunger arrangement (110) inside the syringe housing (101) and prevent further movement of the plunger arrangement (110) in distal direction inside the syringe housing (101) and thus completion of the injection.

[0093] - to ensure most distal sealing member (111) folds to adapt to the reduced inner diameter (105) in the distal end of the syringe housing (101). -to ensure the displacement agent (130) stored in the annulus around the plunger arrangement stem (113) between the most proximal sealing member (112) and the most distal sealing member (111) inside the syringe housing (101), is able to flow pass the folded most distal sealing member (111) once adapted to fit inside the region of reduced diameter (105) inside the syringe housing (101).

[0094] Furthermore, it is an objective to ensure ease of use and reduce risk of mistakes and errors due to wrong use.

[0095] Although the plunger arrangement (110) and plunger rod (120) are illustrated in fig. 1-14 as an assembly of two components, with the plunger arrangement (110) made in a flexible material (e.g. Silicone rubber) and the plunger rod made in a more rigid material (e.g. plastic material), it could also be a single unit made by a 2-component mold.

[0096] In fig. 15 an alternative embodiments of plunger arrangements and means of manipulation are shown. In fig 15a, a plunger rod (120a) is shown featuring an integrated most proximal sealing member (112a). A plunger arrangement (110a) in a more flexible material with a plunger stem (113a) and a most distal sealing member (Illa) is attached to the plunger rod (120a) with integrated most proximal sealing member (112a) by a self-locking fitting (121a) or glued into a simple socket. In a further embodiment shown in fig. 15b, wherein a plunger rod (120b) incorporates an integrated most proximal sealing member (112b) and a stem (113b), whereon a most distal sealing member (111b) is secured.

[0097] The plunger arrangement shown in fig. 15b may provide a stiffer stem (113b) than the plunger arrangement stems 113 and 113a, depending on the choice of material. However, the less flexible material chosen, the worse the sealing properties of the most proximal sealing member (112b) will become. Thus, an embodiment as shown in fig. 15c may be preferable. In this embodiment, a plunger rod (120c) extends into a plunger arrangement stem core (122) on which a plunger arrangement (110c) is fitted. The plunger arrangement (110c) consists of a most proximal sealing member (112c), a plunger stem sleeve (113c) and a most distal sealing member (111c). This design prevents the risk of the plunger stem (113, 113a & 113b) bending instead of the most distal seal folding and adapting to the reduced inner diameter of the syringe housing.

[0098] In a further embodiment shown in fig. 15d, a plunger arrangement (llOd) having a most proximal sealing member (112d) and a most distal sealing member (llld), separated by a plunger arrangement stem (113d), is fitted with a stem protrusion (114) to engage with the region of reduced inner diameter (105) prior to the most distal sealing member (llld) reaching the transition zone (107). This will stabilize the stem (113d) and reduce the risk of bend and collapse. The protrusion (114d) will also displace most of the volume in the syringe neck (103) of the housing and thus reduce the mechanical dead space of the syringe, reducing the required volume of displacement agent to be stored in the annulus around the stem (113d) between the two sealing members (llld & 112d) inside the syringe housing. The protrusion (114d) may contain one or more grooves (115d) to allow medicinal agent (170) and displacement agent (130) to pass during injection. Such a protrusion (114d) with one or more grooves (114d) may also be introduced in a solution wherein the plunger rod (120c) has an extension into a plunger arrangement stem core (122), as described above, by extending the stem core (122) of the plunger rod (112c) further into a protrusion (114c) provided with one or more grooves (115c).

[0099] In a further embodiment shown in fig. 15e, a plunger arrangement (llOe) is fitted with multiple sealing members (116) along the stem (113e) between the most proximal seal (112e) and the most distal seal (llle). This design stabilizes the stem (113e) and reduce the risk of the stem (113e) bending and collapsing. As the most distal seal (llle) enters the region of reduced inner diameter (105) inside the syringe housing (101) and folds, it no longer seals. Thereby the second-most distal sealing member becomes the most distal sealing member (llle*), which then enters the region of reduced diameter and folds, whereby the third-most distal sealing member becomes the most distal sealing member, and so forth, according to the invention and the descriptions of the subject matter related to figs 2-14.

[0100] The embodiment shown in fig. 15f shows a plunger arrangement (llOf) having a most proximal sealing member (112f) and a most distal sealing member (lllf) separated by a plunger arrangement stem (113f), wherein a number of fins (117) in longitudinal direction aids the stability of the plunger stem (113f). As the most distal sealing member (lllf) reach the region of reduced inner diameter (105) inside the syringe housing (101) and folds to adapt to the inside of the reduced diameter (105), the fins (117) deform and adapts to the reduced inner diameter (105) of the syringe housing.

[0101] The features described above related to the different embodiments of plunger arrangements illustrated in fig. 15 can be combined and the claimed invention includes all conceivable combinations within the subject matter as defined by the claims, although not all combinations and variations of the described features are illustrated, as the illustrations are only exemplary. During injection, an operator of a syringe such as illustrated in figs. 1-14, will experience a significant increase in required force to be applied on the plunger rod (120), to enable the most distal sealing member (111) to fold and deform while passing the transition zone (107) between main inner diameter (106) and region of reduced inner diameter (105) inside the syringe housing (101), which may be followed by a sudden decrease of required force, once the most distal seal has folded and adapted to the reduced inner diameter region inside the syringe housing, causing the operator of the syringe to accidently increase the injection flow rate (volume / time) and push the plunger to its end-of-travel very suddenly.

[0102] Finned plunger arrangements as shown in figs. 15e and 15f (radial and axial fins) may reduce the sudden reduction of force required and make the injection flow rate more controllable during the final stage of the injection.

[0103] To reduce the sudden increase in required force for folding and adapting the most distal seal to fit inside the region of reduced diameter (105) of the syringe housing (101), different provisions for preparing the most distal sealing member for folding and / or ensuring a more gradual folding to make the increase of required force on the plunger rod (120) smaller and less sudden, can be introduced to the transition zone (107) between the region of main diameter (106) and the region of reduced diameter (105) inside the syringe housing (101).

[0104] The transition zone (107a) between the proximal region of main diameter (106a) and the distal region of reduced diameter (105a) may be made longer than the region of reduced diameter as illustrated in fig. 16a or the region of reduced diameter may be a region of increasingly reducing inner diameter, as illustrated in fig. 16b, where the region of reduced diameter (105b) is limited to an infinitely short section of the most distal region of the syringe housing (101). This will provide a slower and constantly increasing deformation of the most distal sealing member (111) at he the plunger arrangement (110) moves towards the distal end of the syringe housing (101) and not result in a sudden decrease of required force and resulting accidental acceleration of injection flow rate. However, this embodiment will also reduce the volume of air displaced by the diameter decrease and thus require a longer distance between most proximal and most distal sealing members to provide the same displacement volume. This will further increase the minimal dose size the syringe can be designed for, as the most distal sealing member cannot be allowed to be operated inside the transition zone or the region of reduced diameter during filling, bleeding and dose size adjustment.

[0105] The same drawbacks are to some extend related to a solution shown in fig. 16c, in which the transition zone is asymmetric. This allows a more gradual deformation and folding of the most distal sealing member and thus a more gradual increase in required force to operate the plunger rod, but decrease the volume being displaced by the diameter reduction and increasing the minimum dose size the syringe can be designed for.

[0106] In a fourth embodiment, the length of the transition zone (107d) is relatively short, but a number of longitudinal protrusions (118) prepares the folding of the most distal sealing member (llld), whereby the folding is already initiated when the most distal sealing member (llld) reaches the transition zone (107d). This provides a smoother transition from unfolded to folding state of the most distal sealing member and thus, a more gradual increase in force required on the plunger rod (120) to deform the most distal sealing member (llld).

[0107] The objective of the presented invention is to reduce waste of medicinal agent remaining inside the dead space of syringe and needle unit after an injection. As a given volume of medicinal agent remaining in the dead space of syringe and needle is a larger relative waste for smaller doses than for larger doses, the invention is of particular relevance for syringes designed for administering small doses. The smaller a dose to be administered, the smaller a diameter syringe is needed to maintain a given accuracy of dose size adjustment. Hence, the invention disclosed is of particular relevance to small diameter syringes. The smaller main diameter of the syringe housing is required to be, the smaller the diameter in the region of reduced diameter has to be. However, the smaller the diameter of the most distal sealing member is and the smaller it has to become in diameter to fit inside the region of reduced diameter, the smaller the openings in the folds of the deformed most distal sealing member (105) will become. To ensure flow pass the folded most distal seal inside the region of reduced diameter (105), one (fig. 17a) or more (fig. 17b) flow channels (119) may be provided in the region of reduced diameter, such as illustrated in fig. 17. More flow channels, wider and deeper flow channels will reduce flow resistance and require less deformation of the most distal sealing member and thereby decrease the amount of additional force to be applied on the plunger rod for folding and deformation of the most distal sealing member, but at the same time also decrease the volume of displacement agent being displaced.

[0108] The features described above related to the different embodiments of transition zones and flow channels illustrated in figs. 16 and 17 can be combined and the claimed invention includes all conceivable combinations within the subject matter as defined by the claims, although not all combinations and variations of the described features are illustrated, as the illustrations are only exemplary. The region of reduced diameter (105) inside the syringe housing (101) may be an integral part of the syringe housing component design, as shown in fig. 1-17, but may also be provided by a separate component inserted in the syringe housing. Such a solution enables the use of different materials for the syringe housing and the diameter reducing insert and allows the diameter reducing insert to be made in a more flexible material than the syringe housing. Examples of syringe embodiments provided with diameter reducing inserts is shown in fig. 18. In fig. 18a a simple diameter insert (400a) is inserted in a syringe housing (1801), providing a syringe body (1800a) with an interior shape identical to the single-component syringe housing (101) illustrated in fig. 1-14.

[0109] In fig. 18b, a syringe housing (1801) is shown with a diameter reducing insert (400b) having longitudinal protrusions (418) to initiate the folding of the Most distal sealing member (111) of the plunger arrangement. The diameter reducing insert (400b) is also provided with a flow channel (419) to allow displacement agent from the annulus between the most proximal sealing member (112) and the most distal sealing member (111) to pass by the most distal sealing member, once the most distal sealing member enters the region of reduced diameter (405). In this particular embodiment, the flow channel is provided by a cut-out section of the wall of the diameter reducing insert (400b). In a further embodiment, shown in fig. 18c, a diameter reducing insert (400c) is made with multiple flow channels (419c) in the outer surface of the diameter reducing insert (400c). This prevents the flexible folding most distal sealing member (111) of the plunger arrangement (110) to expand partially into the flow channel (419) and limit the flow.

[0110] A diameter reducing insert (400 a-c) as illustrated in fig. 18 may be fixed in the most distal end of a syringe housing (1801) by adhesive, welding, 2-component molding or by friction. Diameter reducing inserts made in a flexible, rubber-like material may be made with a slightly oversized outer diameter and pressed into the distal end of a syringe housing (1801). A diameter reducing insert (400d) may also be fixed by small protrusions (1818) on the inside of a syringe housing (1801d), where the protrusions (1818) will work as both locks securing the diameter reducing insert (400d) as well as fold-advisors initiating folding of the most distal sealing member (111) as the most distal sealing member (111) pass the protrusions (1818) and enters the transition zone (1807).

[0111] It will be obvious to the skilled person, that a syringe as described in the above and illustrated in fig. 1-18 introduces a risk of the operator pushing the plunger arrangement as far towards the distal end of the syringe housing as it can get, as this would be the normal procedure when filling a standard syringe, to minimize the air in the syringe having to be bled out. With a syringe according to the invention, such handling would result in the displacement agent being expelled and most likely medicinal agent being sucked into the annulus around the stem (113) of the plunger arrangement (110) between the most proximal sealing member (112) and the most distal sealing member (111). However, AD Auto Disable) syringes with the purpose of ensuring they can only be used once, are often required for use for vaccination purposes. Such syringes have built-in means for preventing the plunger arrangement from being pulled back (towards the proximal end of the syringe, once the plunger arrangement has been moved towards the distal end. The means of limitations of plunger arrangement movement, are either fitted to a plunger rod (120) and engaging with the syringe housing (101) or an integral part of the means of actuation (120) of the plunger arrangement. Hence, such syringes are normally delivered with the plunger arrangement not at its most distal position and not intended for operation in distal direction until after filling. Operating a syringe according to the invention will thus be no different than operating any standard AD syringe. Moreover, combining known means of achieving AD functionality with a syringe according to the invention, would prevent a syringe being handled wrong to be accidently used, as the AD mechanism would prevent filling of a syringe wherein the plunger arrangement has been prematurely moved to its most distal position inside the syringe housing.

[0112] Besides being compatible with known AD mechanisms ensuring single use of a syringe, the characterizing features of the invention also presents an opportunity to introduce new means of achieving an Auto Disable functionality. Two examples of embodiments with built-in auto disabling functionality are shown in figs. 19 and 20. In fig. 19a a syringe housing (101) contains a plunger arrangement (110) with a most proximal sealing member (112) and a most distal sealing member (111) separated by a stem (113), wherein a piece of stainless-steel or other metallic material (1901) is pre-bend and molded into the stem (113) of the plunger arrangement. The horizontal distance between the ends of the stainless-steel piece is slightly larger than the reduced inner diameter (105), but not large enough to touch the wall of the syringe housing (101) in the region of main inner diameter (106). This allows the plunger arrangement to be operated in both proximal and distal direction, as long at the stainless-steel piece (1901) does not enter the region of reduced inner diameter (105).

[0113] As the plunger arrangement (110) moves towards the distal end of the syringe housing (101) during injection, the most distal seal (111) starts to deform when reaching the transition zone (107), as illustrated in fig. 19b. The most distal seal (111) deforms and enters the region of reduced diameter (105), the stainless-steel piece (1901) reaches the transition zone (107) and 1 is subjected to elastic deformation, illustrated in fig. 19c. The deformation builds up tension in the stainless-steel piece, like a small spring.

[0114] In fig 19d, the plunger arrangement (110) has been moved towards the distal end of the syringe housing (101) during injection and the piece of stainless steel (1901) has been elastically deformed to adapt to the reduced inner diameter (105). This means, that the plunger arrangement (110) can no longer be pulled back in proximal direction, as the edges of the stainless-steel blade or wire (1901) will dig into the softer material of the reduced inner diameter (105) region of the syringe housing (101) and jam at the slightest movement of the plunger arrangement (110) in proximal direction. The plunger arrangement can however still move in distal direction inside the syringe housing (101), until the plunger arrangement (110) meet its end of travel, where it will be stuck. The means of connection between the plunger arrangement (110) and the plunger rod (120) may be designed to snap, if excessive force is used to try and pull back the jammed plunger arrangement (110) towards the proximal end of the syringe housing (101). This ensures that the syringe can only be used once, as well as ensuring the syringe cannot be filled after faulty operation of the syringe, having pushed the plunger arrangement (110) to its most distal position prior to filling.

[0115] A similar functionality is obtained by the embodiment shown in fig. 20. Here, a syringe housing (101) contains a plunger arrangement (110) with a most proximal sealing member (112) and a most distal sealing member (111) separated by a stem (113). The syringe housing (101) further comprises a diameter reducing insert (400e), fixed at the most distal end of the syringe housing (101). The diameter reducing insert (400e) has in its proximal end a transition zone (107) reducing the inner diameter from the main diameter (106) of the syringe housing into smaller diameter (105) of a short length in distal direction, and a slightly increased inner diameter (1902) in the remaining length of the insert in distal direction. The diameter reducing insert (400e) furthermore comprise a flow channel (419) in its inner surface.

[0116] In fig. 20a the most distal sealing member (111) is passing thought the small length of reduced inner diameter (105) during injection and in fig. 20b the most distal sealing member (111) has just passed the small length of reduced inner diameter (105) and entered the region of slightly increased diameter (1902), which allows the folded and deformed most distal sealing member (111) to unfold slightly. Once the most distal sealing member (111) has entered the region of slightly increased inner diameter (1902), the plunger arrangement (110) can no longer be moved further back in proximal direction, as there is no room for the folded most distal sealing member to unfold and refold in the opposite direction. The plunger arrangement (110) is not stuck or prevented from being moved further in distal direction and then back in proximal direction, but it cannot go further back in proximal direction than the position illustrated in fig. 20b. This prevents the syringe from being reused and filled again.

[0117] As the reduction of inner diameter is only required to appear at the most distal end of the syringe housing in a syringe according to the invention, a diameter reducing insert does not necessarily have to be fixed at the distal end of the syringe housing. In the embodiment shown in fig. 21, a diameter reducing insert is introduced to a syringe housing (1801), but not fixed in axial direction inside the syringe housing (1801). During injection, gravity will ensure the insert (500) shown in fig. 21a will slide to the most distal end of the syringe housing (1801), provided that the proximal end of the syringe is pointed in an upwards direction and the density of the diameter reducing insert (500) is higher than the density of the medicinal agent. Otherwise, the most distal sealing member (111) will push the diameter reducing insert (500) towards the most distal end of the syringe housing (1801), provided the friction force between the diameter reducing insert (500) and the syringe housing (1801) is less than required to fold and deform the most distal sealing member (111), as shown in fig. 21b. The most distal sealing member (111) will thus only deform and enter the diameter reducing insert (500) once the diameter reducing insert (500) is positioned as far in distal direction it can get inside the syringe housing, as illustrated in fig. 21c.

[0118] Numerous variations, substitutions, modifications and simplifications of the illustrated and described components may still be within the subject matter as defined by the claims.

[0119] Even though the foregoing embodiments represent the most preferred at present, those of ordinary skill in the art will recognize many possible alternatives that we have not expressly suggested here. While the foregoing written descriptions enable one of ordinary skill to make and use what is considered presently to be best modes of the invention, those of ordinary skill will understand and appreciate the existence of variations, combinations, and equivalents of the specific embodiment, method, and examples herein. It should be understood that the drawings and detailed descriptions herein are to be regarded in an illustrative rather than a restrictive manner, and are not intended to limit the invention to the particular forms and examples disclosed. To the contrary, the invention includes any further modifications, changes, rearrangements, substitutions, alternatives, design choices, and embodiments apparent to those of ordinary skill in the art, without departing from the subject matter of this invention, as defined by the claims included herewith or later added or amended in an application claiming priority to this present filing.

Claims

A syringe for injection of an active substance comprising:- a cylindrical syringe body (101) with a limiting wall (102) in the distal end of said syringe body. Said limiting wall (102) transitioning into a neck (103) or having an opening (104)5 suitable for the active substance to be delivered through.- said cylindrical syringe body including a region of reduced inner diameter (105).- a plunger arrangement (110) axially displaceable in the axial direction inside of said syringe body.- said plunger arrangement provided with means of actuation (120) in axial direction of10 said syringe body.- said plunger arrangement has at least two sealing members (111, 112) spaced apart in axial direction by a plunger stem (113), providing circumferential seals against said cylindrical syringe body (101).Wherein:15 Said region of reduced inner diameter (105) is located in distal direction of most proximal sealing member (112) of plunger arrangement (110) and proximal to said limiting wall (102) of said cylindrical syringe body (101).Said syringe is adapted for drawing a fluid active substance (170) into the cylindrical syringe body through said opening (104) in said limiting wall (102) or through said neck20 (103) in which said limiting wall (102) may transition into, by manipulation of said plunger arrangement (110), and said syringe is further adapted for said fluid active substance to be accommodated inside said cylindrical syringe body (101) between said limiting wall (102) and said plunger arrangement (110).Characterised by:25 Said sealing members (111, 112) of plunger arrangement (110) are configured for providing at least one sealed volume (130) in an annulus between plunger arrangement (110) and cylindrical syringe body (101).Said plunger arrangement (110) is configured for engagement with said region of reduced inner diameter (105) and said region of reduced inner diameter (105) is30 provided with means (107) to deform at least most distal sealing member (111) ofplunger arrangement (110), such that said plunger arrangement (110) is adapted to partly slide into said region of reduced inner diameter (105).

2. A syringe according to Claim 1 wherein said region of reduced inner diameter (105) of5 syringe body (101) is a separate component (400 a-d) inserted in a cylindrical syringe housing (1801) to provide a syringe body (101).

3. A syringe according to claim 1 wherein said region of reduced inner diameter (105) of syringe body (101) is a separate component (400 a-d) inserted and fixed in a cylindrical10 syringe housing (1801) to provide a syringe body (101).

4. A syringe according to any of claims 1-3, in which a sealed volume (130) in the annulus between plunger arrangement stem (113) and cylindrical syringe body (101) and most proximal and most distal seals (112, 111) of plunger arrangement (110) seals against15 cylindrical syringe housing (101), is filled with a gas.

5. A syringe according to Claim 4 in which said gas is sterile air.

6. A syringe according to any of claims 1-3, in which a sealed volume (130) in the annulus20 between plunger arrangement stem (113) and cylindrical syringe body (101) and most proximal and most distal seals (112, 111) of plunger arrangement (110) seals against cylindrical syringe housing (101), is filled with a fluid.

7. A syringe according to Claim 6 in which said fluid is sterile saline solution.

258. A syringe according to any of claims 1-8 wherein at least one recess (119) in the region of reduced diameter (105) is adapted for fluid and / or gas to pass plunger arrangements most distal seal (111) of said plunger arrangement (110).

9. A syringe according to any of claims 1-9 wherein said limiting wall (102) in said cylindrical syringe body(lOl) transitions into a neck (103) and a protrusion (114) on the distal end of the plunger arrangement (110) is adapted to displace part of the volume inside said neck (103).

510. A syringe according to claim 9 wherein at least one recess (115) in said protrusion (114) displacing part of the volume inside said neck, is adapted for fluid and gas to pass through said neck (103).10 11. A syringe according to any of the claims 1-10, in which said plunger arrangement (110) is a single component or unit.

12. A syringe according to any of the claims 1-10 in which the plunger arrangement (110) is an assembly of two or more components.1513. A syringe according to claim 12, wherein the most proximal seal (112a) of the plunger arrangement assembly is part of a plunger actuation component (120a-figl5a).

14. A syringe according to claim 12, wherein the most distal seal (111) of the plunger20 arrangement assembly is part of a plunger component.

15. A syringe according to any of the claims 1-14, wherein the plunger arrangement (110) is configured with one or more volume displacing and / or stabilizing ribs (116 / 117) between most proximal (112) and most distal seals (111) of plunger arrangement.2516. A syringe according to claim ,15 wherein said ribs (116 / 117) are configured to act as seals and able to deform to enable accommodation inside region of reduced diameter(105).

17. A syringe according to any of claims 1-16, wherein a plunger arrangement (110) is adapted to engage with a region of reduced diameter (105) in the distal end of a syringe body (101), wherein said plunger arrangement (110) is fitted with means(1901) of preventing movement in proximal direction once said means (1901) have5 entered said region of reduced inner diameter (105) inside said syringe housing (101).

18. A syringe according to any of claims 1-17, wherein a plunger arrangement (110) is adapted to engage with a region of reduced diameter (105) in the distal end of a syringe body(lOl), wherein said region of reduced diameter (105) is fitted with means10 (1902) of preventing movement of plunger arrangement (110) in proximal direction once said plunger arrangement (110) have entered said region of reduced inner diameter (105) and most distal sealing member (111) have expanded and engaged with said means (1902) inside said region of reduced diameter (105).15

Images