Filling apparatus, useful for containers for pharmaceutical uses, comprises support and locating device, gauged cylinder unit, closure device, actuating device, and programmed control device

ES 2 255 772 B1

DESCRIPTION

Apparatus for filling containers for pharmaceutical and similar uses.

The present invention refers to an apparatus for filling containers intended for pharmaceutical and similar uses, that is, an apparatus for single or repetitive automatic dosing, with programmable volume and proportions, of solutions of various kinds, to destination containers of different formats. . The dosage will be carried out through the use of replaceable sanitary equipment when changing the formulation that will avoid any contact between the device, the substances used and other drugs.

The application of the invention is to prepare, in the appropriate dose and concentration for each patient, solutions that will be subsequently administered intravenously, starting from substances contained in containers of any presentation, volume and concentration.

The apparatus object of this patent has two functions, which can be used either separately or together. On the one hand, it can prepare formulations in solution, starting from stock solutions, according to a pre-established program and that can be dosed into containers (generally vials), in sterile form or not, depending on whether or not the The formulation resists or not a heat sterilization process, or it can be dispensed sterile, due to the effect of filtration through membrane filters. In this case, since the efficiency of the filtration to guarantee sterilization depends on the integrity of the membrane, the device automatically checks it by means of the so-called bubble point. Dispensing to the definitive containers must be carried out with the maximum guarantees of sterility, either in laminar flow cabinets or the optimal solution, consisting of flexible plastic containers, which already have a membrane filter incorporated prior to their sterilization. immovable.

The main application of the apparatus object of the present invention lies in allowing the solution to be administered with the appropriate composition to be prepared in the hospital pharmacy services themselves. The device that is the object of the Spanish Utility Model no. 9300684 It was also intended for filling pharmaceutical application containers, especially for infusing solutions, but in said Utility Model, the apparatus was of the gear pump type with which the solutions handled in the apparatus came into contact, requiring a Thorough cleaning when changing the type of solution. Also, the dosed volume was controlled by weight.

The objective of the present invention is to achieve an apparatus in which an easy combination of various components of a medicinal solution is achieved, without the need to proceed to the subsequent washing of the internal organs of the apparatus, allowing the programming of the doses in a volumetric way with programming previous dose by the operator and dosing automatically, accurately and safely.

An essential part of the present invention is that the apparatus object of the same has means to actuate a displacement element of a piston and cylinder assembly that acts as a pump, effecting the aspiration and expulsion by the controlled movement of the plunger and having means for opening and closing a series of conduits of a distributor assembly that connects the apparatus with the different containers for the components of the solutions and the final containers destined to contain the themselves, as well as air to carry out the bubble point test of bags that have a sterilizing filter as disclosed in the object of Spanish Utility Model No. 9103692.

In the case of filling said bags or other containers with a sterile presentation filter, starting from solutions of origin that are also sterile, the apparatus object of the present invention will carry out a filter integrity test, compressing air at a pressure slightly lower than the point of filter bubble for the last dosed substance and checking that the pressure does not drop for, for example, 5 seconds, evidence that the air at that pressure cannot overcome the surface tension of the liquid that clogs the pores, showing that the diameter of the pores is correct and that the filter is not damaged.

Therefore, the apparatus object of the present invention comprises an electromechanical apparatus that, installed mainly in hospital pharmacy services, allows the operator (personnel trained as laboratory technicians) to program the doses and proportions necessary for each patient, making the apparatus dosing automatically, accurately and safely. The design of the device, as well as the different functions it presents, provides all the information (visual through the screen and printed through a printer or external PC) and control devices (keyboard) necessary for the operator to carry out the procedure.

The apparatus will be especially suitable for the use of devices made up of a plunger and piston element, for example, a syringe, with a distributor attached to the pump and to the set of starting and receiving containers for solutions and air, which will be completely removable as it is a single-use device that is essentially composed of a syringe as a means for driving and controlling the dose and a distributor whose outputs are selectively clamped by the valves of the invention to regulate the flow of liquids during the process. Said distributor has several conduits, for example six, that communicate with a common central point of the distributor and that can be put in communication with each other in the previously programmed way. A first conduit is connected to the plunger pump, for example, an impeller syringe, a second is used as an air inlet through a membrane filter, a third is connected to a waste container for liquids left over from the purges, a fourth is connected to the destination container and a fifth to the container with the source solution, if the procedure is limited to the fractionation of a container into individual doses for patients. If the concentration of the source solution is modified with the addition of a diluent, the container with said diluent is connected to the sixth conduit of the distributor. If this is not the case, said sixth conduit is sealed by means of a plastic piece inserted therein.

If the source solution is in non-sterile form in a container, an extender can be attached to the sterile single-use device, which facilitates

ES 2 255 772 B1 the connection to said container. Said extender is essentially composed of a tube with a male luer-lock connector at one end and a twist-off valve at the other.

If the source solution is in bottles with a small volume in relation to the dose required for patients, it is possible to connect to the sterile single-use device a sterile single-use device that allows the aspiration of the liquid from up to six connected bottles simultaneously. Likewise, it is possible to insert the suction tube of the disposable single-use equipment into a housing in the front of the apparatus that, by means of an optical detector, allows the detection of the exhaustion of the original containers.

The procedure basically consists of a series of successive operations that are synthetically indicated below.

a) Prepare the device (start-up and programming of the dosage parameters: substance / s to be used and its dosage parameters, dose, concentration, operating mode) and give the order to execute the procedure.

b) Install the single-use device in its housings on the front of the appliance.

c) Install the container / s with the substance / s of origin in the support / s of the device.

d) Puncture the container / s with the substance / s of origin with the spine / s connected to the distributor.

e) Connect the destination container.

Once these operations have been carried out by the user, the device will continue the procedure according to the programmed parameters, as synthetically indicated below:

a) Aspirate a small volume of liquid to purge the single-use device lines.

b) Remove the air from the purge remaining in the syringe to the waste container.

c) Aspirate the programmed volume (if it is greater than 50 ml, the dosage is divided into repetitive cycles of 50 ml and the last with the rest less than 50 ml).

d) Unload the liquid from the syringe to the destination container.

e) If the programmed dose has not been completed, repeat steps c) and d).

f) Once the dose is completed, if the destination container has a 0.22 μιη filter, aspirate air and try to discharge it into the destination container at the integrity test pressure programmed for the solution used. If dosing is not possible, the filter will be considered correct.

g) Print a label with the composition of the destination container and the result of the integrity test.

Once the destination container has been filled, the device will allow the user to repeat the process as many times as desired, being possible by modifying the dose and concentration of the preparation. It will not be possible to modify the source substance (s) without discarding the single-use device.

If any source substance runs out during the procedure, the device will aspirate air and, before discharging the liquid from the syringe to the destination container, it will detect the presence of said air, checking that the contents of the syringe are compressible. alerting the user of such a situation and allowing him to replace the exhausted source container and continue normally (after purging the single-use device) or dose the liquid portion of the syringe content to the destination container and end the procedure.

If the user wishes to detect the exhaustion of the source solution before the aspirated air reaches the distributor and the syringe, and said source solution is of sufficient transparency, it is possible to introduce the conduit of the single-use device that is connected to the source container. in a housing provided on the front of the device, where an optical device will allow detecting the exhaustion of the solution.

The device will make it possible to identify the users who make the preparations by means of a name and an access code. The user's name will appear on the printed label to allow traceability.

Figure 1 shows, in a simplified way, the set of component parts of the apparatus object of the present invention, which make it possible to implement the procedure object of the same.

Figure 2 shows a simplified view of the tube pinch valve mechanism.

Figure 3 shows a simplified perspective view of the apparatus object of the present invention.

Figure 4 shows a simplified view of the sterile single-use device.

Figure 5 shows a simplified view of the extender for filtering non-sterile source solutions.

Figure 6 shows a simplified view of the arrangement of the elements in the apparatus during a fractionation process of source solutions with a mixture of two substances to modify the concentration.

Figure 7 shows a simplified view of the arrangement of the elements in the apparatus during an addition procedure to prepare doses greater than the volume of the individual source containers.

Figure 8 shows a simplified view of the sterile single-use device that allows the connection of 6 bottles simultaneously.

According to the figures, and in particular, according to the schematic representation of figure 1, the apparatus object of the invention comprises a sterile single-use device composed, for example, of a cylinder and piston pump, for example , the syringe (1) and a distributor (12), which will be inserted into the housings provided for this purpose on the front of the device. An electronic card (9) will generate electrical impulses to the five valve motors (11) and the motor (7) for driving the plunger (2) of the syringe (1) to control the aspiration and discharge of liquid and air according to the user-programmed parameters. Each of the valves (11) is formed by a fixed part (45) and a mobile part

ES 2 255 772 B1 (46) (figure 2) that seals or releases the passage of the liquid through the conduit inserted between the two. The moving part (46) is linearly displaced by a spindle (47), whose nut (48) is fixed to said moving part (46). Said spindle (47) is also driven by a motor (not shown). The volume measurement will be carried out indirectly by the relative optical encoder (8) coupled to the motor (7) for driving the piston (2). A spindle (5) coupled to this motor (7) by means of the coupling (6) generates the linear movement of the plunger (2) of the syringe (1) that is installed in the housing (3) that moves jointly with the nut (4) of said spindle (5). The housing body (3) comprises a load cell, not shown, which converts the force exerted on said piston (2) into an electrical signal that is processed by the control card (9) so that knowing the diameter of the piston (2) and the force exerted on it, it will be possible to indirectly obtain the pressure of the fluid inside the syringe (1) and, therefore, govern the motor (7) by means of a control algorithm that ensures that said pressure corresponds to that programmed by the user.

The information exchange with the operator will be carried out by means of the keyboard and screen (10). The operator will program the characteristics of the solutions and the doses and concentrations of the preparations, as well as other auxiliary functions, and will receive information on the status of the procedure at all times.

According to the figures, and in particular, according to the schematic representation of figure 6, during a fractionation procedure the container with the source solution (13) will hang from the support rods (16) (or -39- , figure 3, if it is a bottle). In case of mixing solutions, the second container (14) will also hang from the support rods (17). The destination container, in the case of figure 6, a bag (15) with a 0.22 μm filter (18), will be hung on the support (19) that will be fixed at the desired height on the bar (21) by means of the thumb (20). The sterile single-use device will be inserted into the front of the device. The syringe (1) will be fixed on the upper (28) and lower (29) supports. The plunger (2) of the syringe (1) in the housing (3). The distributor (12) on the fixed body of the valves (11). The five routes of the distributor (12) (the sixth is connected to the syringe -1-) will be connected as follows: A first to the container of the source solution (13) through the conduit (26) and nailing the punch (24) of its end in the neck (23) of said container. A second to the destination container through the conduit (38) and connecting the male luer connector (22) at its end to the 0.22 µm filter (18). In the case of treating the destination container of a device with a female luer, the male-male luer adapter (40) (figure 4) will be inserted between the male luer connector (22) of the single-use device and said destination container. A third way will be connected to a membrane filter (34) to allow the aspiration of air for the integrity test. A fourth to the waste container (33) through a conduit (30) and connecting the male luer (31) at its end to the female luer (32) inserted in the cap of said waste container (33). A fifth will remain sealed if it is a fractionation or will be connected to the second container with source solution (14) through the conduit (35) and nailing the punch (36) of its end in the neck (37) of said container. If it is desired to use the optical liquid detection device, the conduit (26) must be inserted into the housing (25) of said detector.

Figure 3 shows the body (53) of the apparatus, carrying the supports for bags and containers (16), (16 '), (17), (17'), as well as the support bases (49) and (50), valve body (11) and housings (28) and (29), for the syringe (1), as well as the housing (3) carrying the load cell.

Figure 5 shows a simplified view of an extender (45) for filtering solutions that are not sterile in origin, comprising the terminal couplings (46) and (47), the first of which comprises a "twist-" device. off ". The extender can also be used to fill large bags, of the order of 3 liters, from tanks.

Containers can also be filled starting from different components in separate containers, as can be seen in Figures 7 and 8, in which a multiple collector (41) equipped with several inlets (42), (42 ') can be seen , (42 ") ... for respective containers from which a single container (43) is fed.

According to the figures, and in particular, according to the schematic representation of figures 7 and 8, if the source solutions are presented in bottles, the sterile single-use device for connection of up to six bottles (41) can be used, formed by 6 punches interconnected by the conduits (42), and finished with a twist-off (46) where the punch (24) of the sterile single-use device installed in the device will be nailed. The bottles will be hung on their respective hooks on the support (54), the corresponding punch being driven into each one of them.

Everything that does not affect, alter, change or modify the essence of the apparatus described, will be variable for the purposes of the present invention.