Injecting container

The present invention relates to a device for injecting parenteral injections or infusions. The present invention relates in particular to injection devices which enable the full use of the injectable preparation to be used. The invention also allows the use of an intravenous injection device.

Injection devices have found wide application in the administration of injectable pharmaceutical preparations by parenteral injection or infusion. These types of devices have several important advantages, such as their easy operation and reduced risk of bacterial infection. The injection device generally includes a sleeve that contains liquid injectable formulation. At its front end, the sleeve is terminated with a seal that includes an outlet duct, such as a needle or injection cannula, or infusion tube. At its rear end, the device is closed by a piston that can be moved forward to push the injected preparation out of the device through the discharge duct. This type of injection device is known as a single-chamber injection device.

Two-chamber injection devices are also well known. These types of devices are intended for use with injectable preparations that are always ready for use and their space between the front closure and the rear piston is divided into two chambers that are separated by a sliding wall. The anterior chamber usually contains the solid component of the injected preparation, and the posterior chamber contains the liquid component of this formulation. At a predetermined position in the device, there is a liquid bypass connector in the inner wall of the device, such that the liquid component can bypass the separating sliding wall and flow into the front chamber to mix with the solid component. When forward pressure is applied to the rear piston, this pressure will be transmitted by the liquid to push the sliding wall forward and when this wall is at the level of the bypass connector, the liquid will flow around said wall to mix it with the component in the front chamber. In this way, the two ingredients can be mixed together just before the injection is given, and there will be no time left to decompose the preparation just being mixed. When all the liquid is transferred to the front chamber, the rear piston rests on the sliding wall and by further advancing it will act as a single piston to push the mixed preparation out of the device.

Patent applications No. US-A-4,439,184 discloses a dual-chamber syringe with a double chamber, designed to incorporate two separate liquid bodies one after the other. In a preferred embodiment, antiseptic lubrication and anesthetic lubrication are used to prepare the urethra for catheterization. The features of both anti-septic and anesthetic lubrication make it easier for the C-section to slide into the urethra.

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The purpose and function of single-chamber and dual-chamber injection devices are well known among experts in the field, and there is no need to describe them in detail.

When the administration of the liquid formulation from the injection device is completed and the rear plunger is in the foremost position, there is still some residue remaining in front of the plunger and in the outlet of the device. These debris can be significant, especially when a tube of some length is placed between the outlet and the needle or cannula. This is a disadvantage, which is that a certain amount of the pharmaceutical preparation will not be used by the patient. This disadvantage is even greater when very expensive pharmaceutical preparations such as growth hormones and certain peptides are used.

Various methods have been tried to eliminate this disadvantage. One method was to draw some blood back into the device after the injection, and then inject it again to the patient so that the outlet is flushed out. This practice, however, should not be recommended, as there is a risk that blood components that are very surface sensitive will be destroyed or coagulated to form clots. Another way was to remove the syringe containing the pharmaceutical agent and replace it with a syringe containing the liquid with a rinse such as saline to complete the injection. It is complicated and time consuming, as well as increases the risk of overflow and infection.

The above-mentioned disadvantage is eliminated by the improvement of the present invention.

An injection device according to the invention comprising an outlet duct located at the front end of this device and a piston located inside the device having an additional chamber behind the front piston in the device containing the second liquid, the additional chamber being sealed at its rear end by a rear sliding piston. while at the front end of the device there is a bypass connector allowing the forced flow of a second liquid around the front piston and beyond the front piston through the discharge line, characterized by the fact that the second liquid flowing through the bypass connector located in the additional chamber is the flushing liquid with the discharge line being connected with tube and injection needle or cannula.

The volume of the additional chamber filled with the flushing liquid is at least twice as much as the combined volumes of all spaces in the device before the front piston and the space in the discharge line.

The liquid bypass connector is located in the outer wall of the device.

The liquid bypass connector has the form of a channel in the inner wall of the device or other modifications in the inner wall of the device.

The front piston is located between the chamber with the liquid injectable preparation and the additional chamber with the flushing liquid is elastic and preferably made of butyl rubber.

The sleeve is made of transparent material, preferably of glass.

The injectable liquid preparation is human protein.

Another variant of the injection device according to the invention comprising an exhaust duct positioned at the front end of this device and a piston located inside the device, having behind the front piston an additional chamber in the device containing a second liquid, the additional chamber being sealed at its rear end by a rear sliding piston, while at the front end of the device there is a bypass connector allowing the forced flow of a second liquid around the front piston and beyond the front piston through the discharge line, characterized by the fact that the second liquid flowing through the bypass connector is a flushing liquid, the injection device being a two-chamber, in which the anterior chamber contains the solid component of the injected preparation, and the posterior chamber contains the liquid component of this preparation, the front chamber and rear chamber are separated by a sliding wall and the rear liquid bypass connector is placed in the inner wall of the device causing the liquid component to flow around the sliding wall and mixing it with the solid component and flow to the exhaust duct, while the rear chamber is sealed its back end through the piston

177 284 front, the device having an additional chamber for the flushing liquid behind the front piston, sealed at its rear end by a sliding rear piston.

The flushing liquid volume is at least twice as much as the combined volumes of all spaces in the device in front of the front piston and the spaces in the discharge line.

The liquid bypass connector at the front end of the device is located in the outer wall.

The liquid bypass connector is in the form of a channel in the inner wall of the device, or other modifications in this wall.

The outlet duct through which the flow of the injected preparation is forced is connected to the tube, which in turn is connected to the injection needle or cannula.

Preferably, the solid component is lyophilized human proteins.

The sliding wall between the front chamber and the rear chamber is elastic and preferably made of butyl rubber.

The sleeve is made of transparent material, preferably of glass.

The subject of the invention will be seen in the embodiments of the drawing, in which: Fig. 1 shows the injection device before the injection, Fig. 2 the injection device after the injection but before the rinsing step, Fig. 3 - the injection device during the rinsing step ; Figure 4 shows the injection device after the rinsing step; Figure 5 is a two-chamber injection device before being prepared for injection; FIG. 6 - a two-chamber injection device according to the present invention when preparing it for injection; Figure 7 is a two-chamber injection device after re-feeding the injected preparation to the anterior chamber; Figure 8 is a two-chamber injection device during the intermediate stage after re-introduction of the injected formulation; Figure 9 is a two-chamber injection device in which the flushing solution flows into a chamber formed behind a sliding wall; FIG. 10 - a two-chamber injection device which has been prepared for injection; Figure 11 is a two-chamber injection device during injection; Figure 12 is a two-chamber injection device after the injection has been completed, but before the washing stage; Figure 13 is a two-chamber injection device after the rinsing step.

In the drawings, injection devices are only shown schematically, since the detailed solution is well known to experts in the field. Similar parts in the figures have the same reference numbers. The drawing serves only to illustrate the present invention and not to limit its scope in any way.

Figure 1 shows a single-chamber injection device according to the present invention before starting the administration. The injection device comprises a sleeve 1, which contains the liquid injectable preparation 2, and a chamber containing this preparation, which is sealed at its rear end by means of a front piston 3. At its front end, the device also has an outlet line 4, which is connected to the injection needle or cannula 6 by means of a tube 5.

However, the sleeve 1 extends backwards, where it comprises an additional chamber 9, which is filled with flushing liquid and is sealed at its rear end by a rear piston 10. Moreover, a bypass connector 11 for fluid near the front end of the device is provided. The bypass connector 11 may be positioned in any suitable manner well known to those skilled in the art. For example, it may consist of a channel located in the inner wall of the sleeve 1 or it may have a different form in the inner wall of the sleeve. The bypass connector 11 for liquids can also be of the so-called "reverse" type, in which the interior of the device is equipped in such a way that the piston 3 is deformed when it is in this position. The basic purpose that should be fulfilled by the liquid bypass connector 11 is that the piston 3 does not adhere tightly to the inner wall when it is in the position of the bypass connector 11.

Figure 2 shows a single-chamber injection device after substantially all of the injected formulation has been pushed out of the device. The front piston 3 is located

177 284 is in the most forward position in the sleeve 1, but still a small amount of the injectable preparation 2 remains in the stagnation area in the discharge line 4, tube 5 and liquid bypass fitting 11. In its furthest forward position, the front piston 3 is located at the level of the liquid bypass connector 11 in such a way that a liquid flow path from the chamber behind the front piston 3 around this piston to the stagnant area in front of it is allowed.

Figure 3 shows a single-chamber injection device after starting the leaching step. The rear piston 10 has now been moved forward so that the flushing liquid is forced to flow from the additional chamber 9 through the bypass connector 11 for the liquid around the piston 3 and beyond to the stagnation area in the discharge line 4 and tube 5, thus pushing the injection , already present in the area of ​​stasis, through the injection needle or cannula 6 to the patient.

Figure 4 shows a single-chamber injection device after all flushing liquid has been pushed out of the device. The rear piston now rests on the front piston 3, and the outlet duct 4 and tube 5 contain essentially only flushing liquid 9. In principle, all the injected preparation has already been injected through the needle or injection cannula 6, together with the main flushing liquid, as illustrated by the drop 12.

Figure 3 shows a two-chamber injection device. This device comprises a tubular sleeve 21 that has been divided into a front chamber 22 and a rear chamber 23. The front chamber 22 contains the solid component 24 of the injected formulation, and the rear chamber 23 contains the liquid component 25 of this formulation. The front chamber 22 and the rear chamber 23 are separated by a sliding airtight wall 26, and the rear chamber 23 is sealed at its rear end by the front piston 27. A fluid bypass fitting 28 is provided in the inner wall of the sleeve 21 of the device. An outlet conduit 29 is provided at the front end of the device through which the injection preparation is displaced. The outlet duct 29 is connected to the injection needle or cannula 6 directly through the tube 5 as shown in Figures 1 to 4. For clarity, these details are not shown in Figures 5 to 13.

The abovementioned features of a two-chamber injection device are well known due to prior traditional solutions of two-chamber injection devices.

The sleeve 21 of the injection device of the present invention extends behind the front piston 27, forming an additional chamber 30. The chamber 30 is filled with flushing liquid 31 and is sealed at its rear end by the rear piston 32. Furthermore, a liquid bypass connector 33 is provided on front end of the device.

Figure 6 shows a two-chamber injection device after the rear piston 32 is moved forward so that the sliding wall 26 is placed at the level of the liquid bypass connector 28 and some liquid component 25 is forced to flow from the rear chamber 23 into the front chamber 22. From where, the liquid component 25 is mixed with the solid component 24 to dissolve or suspend to form a ready-to-use injectable preparation. The flushing liquid 31 still remains in the additional chamber 30 between the front piston 27 and the rear piston 32.

Figure 7 shows a two-chamber injection device after all the liquid component has been pushed into the anterior chamber 22. to form the injectable formulation 34 together with the solid component. The front piston 27 now rests on the sliding wall 26, and the rear chamber temporarily does not exist. By moving the rear piston 32 and front piston 27, the secondary chamber 30 with the flushing liquid 31 was moved forward, but in any case did not change its volume.

Figure 8 shows a two-chamber injection device after the rear piston 32 and, as a result, the front piston 27 and, the sliding wall 26 will be moved further forward so that the front piston 27 and the sliding wall 26 cover the liquid bypass connector 28. This connector Bypass 28 is therefore inactive at this stage.

Figure 9 shows a two-chamber injection device after the rear piston is moved further forward so that the front piston 27 is level with the liquid bypass connector 28. With further movement of the rear piston 32, the flushing liquid 31

ΠΊ 284 will begin to flow around the front piston 27 and beyond into the space between the sliding wall 26 and the front piston 27, thus reconstituting the rear chamber 23 and filling them with flushing liquid 31. The injected preparation 34 in the front chamber 22 also moves forward, though still intact.

Figure 10 shows a two-chamber injection device after all the flushing liquid 31 has been pushed into the rear chamber 23. The rear piston 32 now rests on the front piston 27, and the two pistons act as a single piston, while the secondary chamber 30 disappears.

Figure 11 shows a two-chamber injection device after the front pistons 27 and rear 32, and as a result also the sliding wall 26, are moved forward so that the front chamber 22 is filled with the fully injected preparation 34. This preparation can now be pushed out of the device through the outlet conduit 29 so as to begin administering it to the patient. The bypass connector for fluid 28 is now inactive.

Figure 12 shows a two-chamber injection device after essentially all of the injected formulation 34 has been pushed out of the device and administered to the patient. Some part of the preparation now remains in the area of ​​stasis in the device in front of the sliding wall 26 and in the outlet conduit 29 and any tube (not shown) for the needle or injection cannula (not shown). When the sliding wall 26 is in the most forward position, it is located at the level of the front bypass connector for liquid 33, which in this way becomes active and allows the rinsing liquid to bypass the wall sliding 31 34 and the liquid to flow to the stagnant area before wall. With further forward movement of the combined front 27 and rear 32 pistons, the flushing liquid 31 will be forced out through the liquid bypass connector 33 and removed from the device through the discharge line 29 to dislodge the remainder of the injected formulation and push it through the patient needle or injection cannula. From here it is visible. that all the injected preparation will be given to the patient and that nothing will be wasted.

Figure 13 shows a two-chamber injection device after all the flushing liquid has been pushed out through the discharge line 29. Sliding wall 26, front piston 27 and rear piston 32 now abut, and the liquid bypass connector 33 is inactive. Feeding from the device is completed.

The administration of the injectable preparation and subsequent leaching from the single-chamber injection device, as well as the preparation, administration and leaching of the two-chamber injection device is achieved by ejecting the front plunger 3 (Figures 1-4) or the rear plunger 32 (Figures 5-13) to through the piston rod. Such a piston rod can be moved forward due to a simple axial pressure, a screw mechanism, or a combination thereof. Various solutions to achieve this effect are well known to experts in the field, and there is no need to describe them in greater detail here.

The function of the two-chamber injection device according to the present invention is described in the following description.

The injection device is usually delivered to the user as shown and described in Fig. 5. When preparing the preparation device, the user presses the rear piston 32 forward using a suitable piston rod (not shown). This pressure is transmitted by substantially incompressible liquids 25 and 31 in the rear chamber 23 and rear end chamber 30, respectively, so that the sliding wall 26 and the front piston 27 are also pushed forward. When the sliding wall 26 reaches the level of the liquid bypass connector 28, this connector will become active to allow the liquid component 25 to flow around this sliding wall 26 and mix it with the solid component in the front chamber 22. Solid component 24 will be dissolved or dispersed in the liquid component 25 to form an injectable formulation 34.

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When the front piston 27 is moved forward so that all the liquid component is pushed into the front chamber 22, it will lean on the sliding wall 26. Further forward movement of the rear piston 32 will move the front piston 27 and the sliding wall 26 together forward until the front piston 27 will be at the level of the liquid bypass switch 28. This bypass connector 28 will now become active again so that flushing fluid can flow around the front piston 27. With further forward movement of the rear piston 32, the front piston 27 will remain stationary while the sliding wall 26 will be pushed forward and the flushing liquid 31 will bypass the front piston 27 to fill the space created between the sliding wall 26 and the front piston 27. When all liquid the flush will be pushed into this space, the rear piston 32 will rest on the front piston 27, and with further forward movement, these two pistons will act as a single piston.

When the two front pistons 27 and rear 32 are moved further forward, the sliding wall 26 will serve to eject the mixed injection formulation 34 through the outlet duct 29 that has been connected to the needle or injection cannula, possibly through a tube. The injection needle or cannula is now connected to the patient and administration of the injection may occur.

After the administration, the sliding wall 26 is in the most forward position in the sleeve of the device 21, and substantially all of the injected formulation has already been pushed out of the device. However, some of the formulation remains in the stagnant area in the space in front of the sliding wall 26, outlet conduit 29 and attached tube and injection needle. This part will not be consumed by the patient if there are no special circumstances in accordance with the invention.

In the forward-most position, the sliding wall 26 is positioned at the front liquid bypass connector 33 in such a way that a flow path for the flushing liquid around the sliding wall is provided. Further forward pressure on the connected pistons 27 and 32 will then force the flushing liquid 31 to flow around the sliding wall 26 and beyond to the inlet conduit 29 and the tube and needle or cannula attached thereto. After this operation, the flushing liquid 31 will move the remains of the injected preparation so that they are given to the patient, and the outlet duct 29 and the tube are rinsed. In this way no amount of the injected preparation will be wasted. When all the 3L flushing liquid is pushed out of the machine, the feeding is terminated.

An injection device is usually provided in the gripping device to facilitate its use when administering an injection. Such gripping devices are traditional and well known to experts in the field.

The injection device of the present invention does not require any major design changes in known gripping devices. Small changes may be necessary to adapt them to the front bypass connector and the longer device length, but these changes remain within the competence of an expert in this field. The materials used to make the injection devices of the present invention are the same as for conventional injection devices, such as glass and various rubber and plastic materials. Hence, in the case of a device comprising a front chamber which contains a liquid preparation and an additional chamber which contains liquid by flushing the front piston can be made of any elastic material, preferably rubber. However, when the device of the present invention is used for freeze-drying to obtain a solid component, the sliding wall between the front chamber and the rear chamber should be made of elastic material with low water vapor permeability. A suitable material is butyl rubber, preferably halobutyl, such as chlorobutyl or bromobutyl. Therefore, when the device of the present invention is used for freeze-drying, the device sleeve should be made of a rigid material in order to better tolerate the low pressures and temperatures used in the freeze-drying process. A suitable material is glass.

It is important that the volume of flushing liquid is sufficient to thoroughly flush out the stagnant area and remove the remnants of the injected preparation for injection into the patient. It was found that the volume of flushing liquid should be

177 284 at least twice, and preferably at least three times, as much as the combined volume of space in the injection device in front of the front piston or the sliding wall in its forward position and the space in the outlet duct for the injection needle or cannula. This gives the best rinsing effect.

The injection device of the present invention can be used with any of these injectable formulations that have been found to be suitable for conventional injection devices. Therapeutic proteins and peptides may be given as examples. However, the advantages proposed by the present invention become clearer when very expensive preparations, actually those produced as a recombinant DNA product, are administered. Typical examples are growth hormones, certain peptides, anti-cancer drugs, vaccines, interleukins, monoclonal antibodies, tissue plasmin activator (tPA), erythropoietin (EPO), urokinase, streptokinase, low molecular weight heparins and human proteins. More specifically, human proteins are factor VIII, factor IX or antithrombin III, produced as recombinant DNA products. For this type of preparations, avoiding any losses is of great economic importance.

Suitable liquid preparations include, but are not limited to, solutions containing human proteins such as factor VIII, factor IX and antithrombin III, with at least one stabilizing component, such as a surfactant. Suitable solid components of the injectable preparations include, but are not limited to, lyophilized human proteins, preferably factor VIII produced as a recombinant DNA product.

The injection device of the present invention is more widely used for parenteral administration, for example for subcutaneous, intramuscular or intravenous injection. The current device was used only for intravenous injections. More preferably, the injection device of the present invention is used to flush the outlet duct connected to the tube and injection needle or cannula from substantially all of the injectable formulation. The injection device of the present invention is suitably used to administer any human protein, rather than freeze-dried protein.

In the above specification, the present invention has been described with reference to the embodiments shown in the drawing. However, it is obvious to an expert in the field that these embodiments are merely exemplification and are not intended to limit the scope of the present invention in any way. Other variations and modifications of the present invention are possible within the scope of the appended claims.

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