HRP920949A2 - Method and device for injection - Google Patents

Description

The technical field to which the invention belongs

The invention belongs to the field of devices for introducing agents into the body, and especially relates to syringes for injections. Designation according to the International Classification of Patents: A 61 M 5/24.

Technical problem

The invention solves the problem of how to design a device for injecting injections that will allow carrying ampoules with two-component medications and mixing these, usually sensitive, components during injection.

State of the art

This invention relates to devices for injecting injections, particularly for use in ambulatory treatment. More specifically, the invention relates to a device by which a solution for injecting a substance is prepared immediately before injection, or several doses are prepared before the first injection.

Devices for injecting injections in ambulatory treatment where the medication is in solution have been known for a long time and have been widely used, for example, in the treatment of diabetes with insulin. Such devices are usually made so that the patient himself can easily assemble one cylindrical ampoule for one or more doses, one injection needle and a dosing device in one convenient holder, after which he can easily give himself the necessary injection. With this device, ampoules and needles can be easily replaced with new ones. When folded, such injection devices are often shaped like a fountain pen and can be easily carried by the patient.

In addition, the so-called two-chamber or mixing vessels or cylindrical ampoules for preparing solutions of sensitive substances immediately before injection. Such containers are divided into two chambers separated by a movable wall or piston. The sensitive medicament is contained in the anterior chamber in a dry, usually freeze-dried state, and the anterior end of the anterior chamber is sealed by a single wall that can be penetrated by an injection needle. The liquid that needs to dissolve the sensitive substance before injection is in the back chamber. The two chambers are separated by a front movable wall, and the rear end of the rear chamber is sealed by means of a rear movable wall. In addition, there is a connecting channel in the vessel wall that can connect the front and back chambers.

In the pre-injection storage position, there is no connection between the anterior and posterior chambers. The entrance, as well as the exit of the connecting channel, ends in the anterior chamber.

When the container is to be prepared for injection, the rear movable wall in the rear chamber moves forward, and due to the incompressibility of the liquid, the front movable wall will also move forward until it reaches a position opposite the connecting channel in the container wall. When the rear movable wall moves further forward after that, the liquid will be pushed through the overflow channel into the front chamber where it will come into contact with the medication and dissolve it. When injected, these two walls will act together as a single piston and force the prepared injection solution through a single needle inserted through the anterior end wall in the anterior chamber.

In some cases, the medication can be so sensitive that special measures must be taken to protect the substance from mechanical influences at the time of dissolution as well as during further handling of the solution. This applies, for example, to freeze-dried growth hormones where even a simple mixing of the substance and liquid can lead to unacceptable biochemical changes. Therefore, the preparation of the injection container must be carried out with the greatest possible care.

It would be highly desirable to have available a device for injecting injections that can be easily carried and applied like the simple cylindrical ampoules known so far, in which the medication is in a liquid state as a solution, suspension or emulsion, and which at the same time will be able to use the advantages of containers for mixing when injecting sensitive substances.

Description of the solution to the technical problem

According to the invention, a device was created for preparing a solution for injecting one or more substances sensitive to the deterioration of properties, and for injecting this solution.

The aim of the device according to the invention is to prepare a solution, emulsion or suspension in water of one or more sensitive drugs for one or more consecutive injections, using a known multi-chamber cylindrical ampoule, which is sealed at its front end with a membrane that can be pierced by a needle for injections, and is limited from the rear by the front movable wall, then the rear space containing one water phase, which is limited at the front end by the front movable wall, and is limited from the rear by the rear movable wall, as well as a connecting channel made in the wall ampoule between the rear and front spaces, wherein the rear movable wall moves forward and drives the aqueous phase and the front movable wall, until it reaches opposite the overflow channel, so that the liquid phase on further forward movement of the rear movable wall flows past the front movable wall into the anterior space and dissolves, emulsifies or suspends the medication. What is characteristic of the device is that the water phase flows calmly from above through the medicine, avoiding cherry and air mixing.

The device according to the invention is characterized by the fact that it includes:

a) a container for the components of the solution for injection, in which these components are kept separate, but can be mixed by external action to mix and dissolve, which is made in the form of a tube that is hermetically sealed at its front by means of a single membrane that is penetrable, wherein a space between the penetrable wall and one front movable wall holds the solid components of the injection solution, and the space between the front movable wall and one rear movable wall holds the liquid components of the injection solution, while in a connecting channel formed in the tubular wall, placed in such a way that, when the rear movable wall is moved forward together with the liquid and the front movable wall, the liquid can flow past the front movable wall and mix with the solid components and form a solution;

b) a holder in which the container can be fixed so that the components of the solution for injection are brought into contact and mixed, which is made of two tubular elements that can be threadedly connected and encompass the container, so that when these elements are threadedly connected, the front end container with a penetrable membrane is exposed at the front end of the holder to be pierced by the injection needle, the rear movable wall at the rear of the container is moved forward with the liquid and with the front movable wall so that the liquid is forced to flow through the coupling a channel into the space of solid components, in order to mix with them and form a solution;

c) an injection needle holder which is adapted to be placed on the front of the container holder so that the needle can be connected to the interior of the container through a penetrable membrane, and

d) a dosing device connected to the container holder, by the action of which the rear movable wall in the container moves forward, thereby releasing certain doses of the solution for injection, whereby the dosing device is brought to the initial dosing position when the parts of the container holder are threaded.

The invention also includes a more universally usable device for preparing injection solutions from the components placed in the container according to point a) above.

In the following text, the invention is described in more detail with reference to the attached drawings.

One embodiment of the device according to the invention is shown in the drawings.

Figure 1 of the drawing shows a two-chamber cylindrical ampoule having two chambers for use in an injection device.

Figure 2 presents a general view of the injection device according to the invention.

Figure 3 shows the same device in a disassembled state.

Figure 4 is a cross-section of the device in a disassembled state.

Figure 5 shows the device ready for injection.

Figure 6 shows, schematically, the appearance of the first embodiment of the device according to the invention in the position before preparing the injection solution.

Figure 7 shows, schematically, the appearance of the device from Figure 6 after preparation of the injection solution.

Figure 8 represents, schematically, the appearance of the device shown in Figures 6 and 7 when introducing the prepared solution into the injection needle.

Figure 9 shows, schematically, the appearance of the second embodiment of the invention in the position before preparing the solution for injection.

Figure 10 shows, schematically, the appearance of the device from Figure 9 after preparation of the injection solution.

Fig. 11 shows, schematically, the appearance of the device according to Figs. 9 and 10 with the inserted tube, cannula, prepared for injection.

A section of the two-chamber cylindrical ampoule used in the injection device according to the invention is shown in Figure 1. The ampoule consists of a tube 1, preferably made of glass or plastic, which is made with a neck with a flange 2 on its front part. The front part is sealed with a membrane 3 made of rubber or a suitable plastic material, which is attached by a metal capsule 4. The capsule 4 has an opening 5 in its middle part, so that there the membrane 3 is uncovered. The edge part of the capsule is bent around the flange 2, so that the membrane 3 is attached to the front opening of the ampoule.

The ampoule is divided into a front space 6 and a back space 7 by means of a movable partition 8. The rear end of the ampoule is sealingly closed by a movable wall 9, which, at the same time, also seals the rear chamber 7. The two movable walls 8 and 9 can be moved forward in ampoule ensuring sealing against the wall of the ampoule, whereby this ampoule has a circular cylindrical shape for this purpose.

The front chamber 6 of the ampoule contains one or more medications 10 in a dry state, preferably freeze-dried. In this form, even sensitive substances have relatively good stability. The rear chamber 7 contains the liquid phase 11, which is intended for dissolving the dry substance for injection. This liquid phase usually consists of water or physiological saline, and such additional substances as are common in pharmacological practice and may be added to the solution.

In the wall of the ampoule there is a connecting channel, in the form of a depression that is placed and extends in the longitudinal direction of the ampoule. The overflow channel 12 is placed so that it is completely in the front space 6 before the ampoule is prepared for injection, and its length is such that it allows flow past the movable wall 8.

Figure 2 shows the injection device according to the invention in a folded state so that the patient can easily carry it with him. The device is usually shaped like a fountain pen and consists of a front housing 13 that includes a two-chamber cylindrical ampoule according to Figure 1 for the agent to be injected, a rear housing 14 that includes a mechanism for dosing and applying the agents, and a protective cap 15 over the needle for injection. The mechanism for dosing and applying the agent is made in one of the known ways and will not be described in detail here. It usually works in such a way that the control knob 16 on the back of the device is turned so that one index is placed against one scale which determines one suitable dose. When administering drugs, the control button is pressed, which releases a certain dose through the needle. Many different embodiments of such a single drug dosing and delivery mechanism are known in the past and can be used in the injection devices of the present invention.

Figure 3 shows the injection device in a disassembled state. Here the protective cap 15 has been removed so that the front part 17 of the needle with its holder 18 is shown. The needle can be screwed onto the front part of the front housing 13 by means of the holder and can be easily replaced. Thereafter, the protective cap 15 must be kept in place at all times to maintain sterility and should not be removed until just before injection. An opening 19 is made on the front case 13 through which the user can easily check whether an ampoule has been inserted and how much injection solution is left.

The back housing 14 can be screwed into the front housing 13 by means of the thread 20. Simultaneously with this screwing, the inserted two-chambered cylindrical ampoule for injection is prepared, which will be described in more detail in the following text.

Fig. 4 represents a view, partly in longitudinal section, of the disassembled injection device of Fig. 3. Here it is evident that a two-chambered cylindrical capsule of the type shown in Fig. 1 is inserted into the front housing 13 and moved so far forward that its membrane 3 is exposed in order to punctured by a needle. In the rear housing 14, the dosing and dispensing mechanism is shown schematically and marked 22. This mechanism has a forward-directed operating rod 23. By activating it, the two-component cylindrical ampoule is first prepared for injection, after which certain doses of the injection agent can be dispensed using control button 16.

The rear housing 14 can be screwed into the front housing 13 by means of an external thread 20 that engages with an internal thread 24.

Figure 5 shows the device assembled and ready for injection. Here, the rear movable wall 9 is moved so much that it comes into contact with the front movable wall 8. The latter is moved so much that it comes opposite the connecting channel 12 and the liquid phase flows past the front movable wall 8 and mixes with the dry medicament. The pointed back part 21 of the needle also broke through the membrane 3. The two movable walls 8 and 9 in mutual contact were moved so much that all the air from the front space 6 was forced out through the needle. The device is ready for injection.

The operation of the device after it is prepared for injection is as follows:

In the rear case 14, the operating rod 23 and the control button 16 of the mechanism 22 for dosing and distribution are first placed in the initial or zero position. This is done in a manner determined by the construction of the mechanism, which is otherwise known. Then, the back housing 14 is screwed into the front housing 13 until the working rod 23 rests completely on the rear movable wall 9 in the two-chamber cylindrical ampoule.

If the back housing continues to screw, the operating lever will push the back movable wall 9 forward in the cylindrical ampoule, and as the liquid 11 in the back space 7 is essentially

irrepressible, the front movable wall 8 will also be pushed forward. A certain overpressure will occur in the front chamber 6 because the air cannot escape.

When the forward movable wall 8 is pushed sufficiently to be opposite the overflow channel 12, fluid communication between the anterior and posterior chambers will be established. With further forward movement of the rear movable fish 9, the liquid will be forced into the front chamber 6 through the overflow channel 12. At this stage, or stage, the front movable wall 8 will not move.

When all the liquid has been forced into the front space, the rear movable wall 9 will come into mechanical contact with the front movable wall 8. The liquid will dissolve the dry medicament 10 and form an injectable solution ready for use. The holder 18 with the attached needle 17 is then screwed onto the front housing 13, whereby the membrane 3 of the cylindrical ampoule is pierced by the rear tip 21 of the needle, and the excess pressure in the front chamber is released.

By further pushing the control button 16, the operating rod 23 is activated so that the walls 8 and 9 move further forward and the air in the cylindrical ampoule will exit through the needle 17. The device is now ready for injection as shown in Figure 5.

When preparing the device, it is necessary to hold it vertically, with the needle pointing upwards, and the threading must not be done too quickly. In this way, the liquid will calmly climb through the substance and dissolve it, while there is no strong mixing. Such strong mixing is not suitable for many sensitive substances because it can adversely affect the matter.

This is one recommended embodiment where the two-chamber cylindrical ampoule 1 is placed in the front housing 13 and the solid medication is dissolved before the needle 21 pierces the membrane 3 of the ampoule. Since overpressure occurs, the tendency for foaming and blistering is reduced when the liquid and solid material are mixed, which is less harmful to the medication. However, for medications that are not so sensitive, the needle holder 18 with the needle can be screwed onto the front part 13 of the housing before the cylindrical ampoule is inserted and the two housings are screwed together. The rear tip of the needle will then pierce the membrane 3 before the solid and liquid are mixed without overpressurizing the mixing chamber.

When the device is to be used to administer medicine by injection, the protective cap is first removed from the needle. After that, the desired dose is determined using the control button 16 and by pressing the control button, the dose is released through the needle. After that, subsequent doses can be given as long as there is solution for injection in the cylindrical ampoule. After each discharge, the needle is usually replaced with a new sterile needle. This can be easily done by unscrewing the holder 18 with the attached needle from the front end of the injection device and then screwing on a new holder with the needle. At the same time, the rear pointed end of the needle will pierce the membrane and establish a fluid connection to the inside of the ampoule.

The embodiment shown in Figure 6 includes one holder in which the container 1 can be placed. The holder consists of two tubular elements that can be connected by threading, namely the front tubular element 24 and the rear tubular element 28. The front tubular element 24 has a narrowing 25 in at its front end, in which the flange 2 of the ampoule neck 1 can be placed. At its rear part, the front tubular element is designed with an internal thread 28 into which the external thread 27 on the rear tubular element 28 can be screwed. At its rear end, the rear tubular element 28 has closed back wall 29, to which is attached from the inside a stationary piston in the rear tubular element 28, wherein this piston has a diameter smaller than the internal diameter of the ampoule and extends towards the ampoule 1.

When preparing the solution for injection, the rear tubular element 28 is screwed into the front tubular element 24, whereby it is advisable to hold the holder vertically with the tapered neck 25 facing upwards. When the rear tubular element 28 is screwed into the front tubular element 24, the stationary piston 30 will move the rear tubular wall upwards and compress the fluid 11 in the rear space 7. The fluid will exert pressure on the front wall 8 so that the latter will move upwards to a position directly opposite of the connecting channel 12, in which position the liquid 11 can flow calmly through the connecting channel 12 into the front space 6 and mix with the medication 10. While the two tubular elements 24 and 28 are screwed into each other, a very quiet flow of liquid into the front space 6 takes place , which is closed by a membrane at the front end of the ampoule. When the liquid flows into the front space 8, a pressure higher than atmospheric occurs in it, so that a small pocket 31 of compressed gas is formed in the upper end of the ampoule, which is shown in Figure 7, which shows the holder in the position when the tubular elements 24 and 28 are completely twisted into each other, and all the liquid has overflowed into the front space 6. Thanks to the smooth flow of liquid into the upper space 6 at a pressure higher than atmospheric, the formation of foam during mixing is prevented. Of course, the device can be turned several times afterwards, if necessary, to completely dissolve the medication in the liquid.

When the injection solution prepared in this way is discharged, the device is turned to the position shown in Figure 8, with the front part of the ampoule 1 facing downwards, so that the gas in the front space 6 of the ampoule 1 is collected at the upper part and not near the membrane . The solution for injection can be taken by means of a tube, a cannula 32 which is introduced through the membrane and transferred to a conventional syringe 33 for subcutaneous injection in a known manner. It is easier to extract the injection solution from the ampoule 1 thanks to the higher than atmospheric pressure acting in the front space 6 of the ampoule, so that the solution will flow under its own pressure at least initially through the tube, the cannula 32 into the syringe 33 for giving subcutaneous injections.

As mentioned earlier, the second embodiment of the device according to the invention is shown in figures 9 to 11, where it has the same components as the device shown in figures 6 and 7. The main difference is that the device according to figures 9 to 11 is designed to be directly connected to one cannula, a tube, at the narrowed neck 25 of the front ring element 24. In addition, the rear wall 29 of the front tubular element 28 is not closed but has one central opening 34 through which the working rod 35 passes. The working rod 35 is integrally connected with the piston 30 in the last tubular element, wherein the piston is not connected to the last tubular element 28 but is limitedly movable in the longitudinal direction by means of the operating lever 35. As with the device shown in Figures 6 to 8, the outer diameter of the piston 30 is smaller than the inner diameter ampoule 1, but at the same time is larger than the diameter of the opening 34 in the rear wall 29, so that the piston 30 cannot be pulled out of the rear tubular element 28. The two tubular elements 24 and 28 are screwed together and into the other from the position shown in Figure 9, in which the components of the injection solution are completely separated from each other, in the same way as described in connection with the first embodiment according to Figures 6 to 8, until complete mixing is achieved and the device is in the position shown in Figure 10. In this position, the cover 36 is placed on the narrowed neck 25 of the front tubular element 24. In addition, the cannula, the tube 32 is attached to the cover 35, thereby piercing the membrane of the ampoule 1 when the cover is placed on the narrowed neck 25 This is done in a vertical position when the throat 25 is facing upwards. The device is ready to be used as a syringe for giving injections, whereby this is done by pressing the operating rod 35 so that the piston 30 moves the two movable walls 8 and 9 forward into the front space 6 in the ampoule, so that the gas is first removed from the ampoule, then the injection solution is discharged through the cannula 32 in a known manner.

One very practical and simple instrument for preparing a solution for injection is obtained with a device according to the invention. As mentioned above, the device ensures a very calm and safe mixing of the components of the injection solution. If mixing is done too quickly, the result is particle formation and opalescence. Both are expressions of gathering into lumps. It is recommended that the device be made of plastic, and in that case the price of the device will be very low, so the device can be used once. The pitch of the threads on the elements is not critical, but it is recommended that it be within the limits of 0.5 to 10 mm.

It is most convenient for the device according to the invention to be used for subcutaneous injections, but other procedures for administering the injection according to current medical practice are also possible, such as, for example, intramuscular injection.

When the cylindrical ampoule is empty, the injection device is disassembled by unscrewing and the empty capsule is removed. The dosing mechanism is set to zero and after that the device can be prepared for injection again, as mentioned above. The user can easily carry the assembled and prepared device with him to use it at convenient times.

It may be necessary to protect sensitive medications, especially of the polypeptide type, against mechanical action when in dissolved form. Especially critical moments are turning the dried powder into a solution, on the one hand, and on the other hand, further handling of the prepared solution. The latter will be especially important when dealing with preparations for a larger number of doses that must be handled several times.

The use of conventional packaging and syringes does not contribute to the protection against mechanical stress, which, however, this invention provides. The establishment of a solution from a dry powder using the invention is done in a very careful way determined by the construction, so that the medication is spared. As the solution is prepared under a certain overpressure, foaming and formation of bubbles is prevented at this stage. Further handling of the prepared solution will also be very gentle according to the invention. Virtually all the air that was in contact with the solution is removed when the injection device is prepared to give the first injection from the newly installed two-chamber cylindrical ampoule. In this way, the intermediate phase that leads to negative effects on the sensitive medication when handling the container with the solution is avoided, so after that the container can be handled without taking special account of the sensitivity of the solution.

For this reason, it is possible to prepare a single solution that can be used for a longer or shorter time in a gentle way, and to transport the prepared solution without lowering the quality of the sensitive medication due to mechanical stress. This is why the invention enables even sensitive medications to be available for comfortable outpatient treatment.

Medicaments that can be used in the device shown can consist of any substance or mixture of substances that are used in two-chamber ampoules known up to now, or are suitable for this purpose. However, sensitive materials that cannot be stored for long periods of time in solution and that tend to change when dissolved are particularly suitable. Examples of such substances are various polypeptides such as hormones and interferon. It has been found that the invention is particularly suitable for the preparation and injection of growth hormone solutions. They are very sensitive and easily modified when a solution is prepared from them. By using the invention presented in this case, such an impact is significantly reduced. This is extremely unexpected and the experts could not have predicted it.

Dry medications are usually in a freeze-dried or lyophilized state before preparation of a solution for injection from water to which agents for adjusting osmotic pressure, preservatives, etc. are often added, in accordance with current pharmacological practice. It is also possible that the liquid phase itself may contain dissolved substances that may have some pharmacological action that can then be used together with the action of an agent that is later dissolved in the liquid.

Another embodiment is where the liquid may consist of an injectable fat emulsion, such as that described in US Pat. 4 073 943 and 4 168 308. In this case, the dry substance for injection contains a water-soluble or hydrophilic agent that dissolves or disperses in the aqueous phase of the emulsion in the mixture.

The injection device is made of some suitable element such as metal, for example stainless steel or aluminum alloy or some suitable plastic material. The choice of metal is completely within the scope of work of experts.

In addition, it should be noted that the method and device according to the invention are shown in the drawings and described in detail only as examples, and that other embodiments are also possible within the scope of the patent claims.

Claims (4)

1. Device for injecting injections, for preparing solutions of substances sensitive to degradation and for injecting this solution, indicated by the fact that it contains a) a container (1) for the components of the injection solution, in which the components are kept separate but can be brought together by external action to mix and dissolve, and which is made as a tube (1) that is hermetically sealed at its front by means of a membrane (3) which can be penetrated, where in the space (6) between the membrane which can be penetrated and the front movable wall (8) there are solid components (10) of the injection solution, while in the space (7) between the front movable wall (8) and the rear movable wall (9) contains the liquid component (11) of the injection solution, and that in the tubular wall there is a connection channel (12) positioned so that when the rear movable wall (9) moves forward together with the liquid ( 11) and the front movable wall (8), and the liquid can flow past the front movable wall (8) and mix with the solid components (10) until a solution is obtained; b) a holder in which the container (1) can be fixed in such a way that the components of the injection solution can be brought into contact and mixed, which is made of two tubular elements (13, 14) that can be screwed into each other and enclose the container ( 1) so that when the elements are threaded together the front part of the container with the membrane (3) that can be pierced is exposed at the front end of the holder to be pierced by the needle (17, 21) for injections, and that at the rear end is the rear movable wall ( 9) moved forward together with the liquid (11) and the front movable wall (8) so that the liquid (11) is forced to flow through the connecting channel (12) to the space (6) with the solid components to mix and shape them solution; c) a holder (18) for a needle (17) for injections prepared to be placed on the front part of the holder (13) of the container so that the needle (21) can be connected to the space (6) of the container through a membrane (3) that can be pierced; and d) a dosing device (22) with a holder (14) of the container, the action of which forces the movable wall (9) in the container to move forward in a controlled manner, thereby issuing certain doses of the injection solution, whereby the device (22 ) for dosing, set a starting position for dosing when it is attached to the holders (13, 14) of the container with screws. 2. Device for injecting injections, for preparing a solution for injection of medication from substances sensitive to decomposition, characterized in that the components of the solution for injection are kept in a container (1) in which the components are separated, but can be collected to mix and dissolve by external influence and which is made as a tube that is hermetically sealed at its front end (2) by means of a breakable membrane, which contains a space (6) between a breakable wall and a front movable wall (8) in which there are solid components (10) of the injection solution, while in the space (7) between the front movable wall (8) and the rear movable wall (9) there are liquid components of the injection solution, and which has a connecting channel (12) in the tubular wall arranged so that, when the rear movable wall (9) moves forward together with the liquid (11) and the front movable wall (8), the liquid (11) can flow past the front movable wall (8) and mix with the solid components (10) to obtain a solution, and that the device comprises a holder (24, 28) in which the container can be fixed so that the components (10, 11) of the injection solution can be brought into contact and mixed, and which is made of two tubular elements (24, 28) that can be screwed into each other, whereby the front part (2) of the container (1) with a membrane that can be pierced is worn at the front part (25) of the holder, and what is at the rear part of the container ( 1) the rear tubular wall (9) moves forward together with the liquid (11) and the front movable wall (8) by means of a piston (30) placed at the rear part (28) of the holder which pushes the rear movable wall (9) of the vessel, container (1) ) so that the liquid (11) can be made to flow through the connecting channel (12) into the space (6) of the solid components (10) and mix with them until a solution is obtained. 3. The device according to claim 2, characterized in that the piston (30) is immovably placed at the rear part (28) of the holder and that the front part (24) of the holder is designed with one opening directly in front of the membrane that can be pierced in the container, so that is one tube, the cannula can be inserted through the opening and the tearable membrane to withdraw the prepared injection solution for the syringe (33) for giving the injections. 4. Device according to claim 2, characterized in that the piston (30) is made with a working rod (35) that extends through the rear wall (29) at the rear part (28) of the holder, and that one connection to one cannula (32 ) placed at the front part (25) of the holder which can be adapted to the holders (24, 25) and then pierces the membrane of the container (1).