GB2141997A - Method for the preparation of mixtures of pharmaceutical liquids - Google Patents

Abstract

The method entails the use of storage containers (3, 4, 5) for the individual mixture components, in an arrangement with a vacuum chamber (18) to receive a container (14) to be filled and with a connecting hose (7) for each storage container, as well as a hose (13) connected to the container (14) to be filled, which is also joined to the connecting hoses (7) of the storage containers (3, 4, 5). After the desired predetermined amount of each mixture component is dispensed, the connecting hose (7) to the corresponding storage container (3, 4, 5) is clamped and, after the clamping of all the connecting hoses (7), the hose (13) is closed and cut downstream from the clamping. <IMAGE>

Description

SPECIFICATION Method for the preparation of mixtures of pharmaceutical liquids The invention relates to a method for the preparation of mixtures of pharmaceutical Liquids, for example, infusion soLutions; with storage containers containing at least two of the individual mixture components, a vacuum chamber to receive the container to be filled, and with a connecting hose for each storage container as well as a hose connected to the container and connected through a hose connection to the connecting hose of the storage container.

Preparations comprising several different components have to be mixed for the most diverse fields of application in medicine, especially for parenteral feeding in which the individual components often cannot be sterilized or prepared or stored together. For medical as well as practical reasons, a mixed administration is, however, still preferred. In many instances, it is thereffore necessary to prepare the mixture in an additional container which actuaily means preparing a brand new medicine by the hands of a physician or pharmacist. When these mixtures are frequently used, it is often desirable to have them available in storage. It is obvious that this preparation of mixed solutions, such as, for example, mixed infusion solutions, generally penetrates the sealed system of the storage containers, which is most undesirable.The object is therefore to accomplish a virtually contaminationfree preparation of such mixtures, i.e. a preparation without manual manipulation, with the individual components of the mixture having a predetermined proportion to one another.

The state of the art provides for the filling of sterile bag-like containers by pumping in the individual components. The filling amount is determined by the reference output volume of the pump. Additionally, the total mixture is weighed. In addition to the fact that such mixture preparation and filling methods do not meet present demands for rapid processing, the known arrangements are not sealed systems, and thus are not contamination-free.

Furthermore, there is the danger of particles rubbing off from the pump hose. Finally, the dosage system of this apparatus regarding the individual components is not sufficiently reliable, depending solely on the total weight of the mixture. Thus, the individual components might not have the desired proportion to one another.

There is therefore an urgent need for an arrangement which allows extremely rapid filling of containers with a mixture of pharmaceutical liquids, precisely adhering to the predetermined amounts of the individual components, and being contamination-free in a virtually sealed system. By avoiding any handling of the arrangement and the containers during filling, it is possible to prepare such special pharmaceutical liquid mixtures to be used according to medical prescription, and to keep them stored by pharmacists, not by the manufacturers. The air inherent in the system and present, for example, in the racking hose, can be ignored.

The object of the invention designed for a method of the initially described type and in accordance with the basic principle of the invention is accomplished in such a way that, after reaching the desired predetermined amount of each mixture component, the connecting hose to the corresponding storage container is clamped and that, after the clamping of all the existing connecting hoses, the hose is closed and cut downstream from the clamping.

The container, maintained under external vacuum, is connected to the storage containers holding the individual components of the mixture to be prepared through a hose, hose connection and connecting hoses. Because of the vacuum effect, all mixture components can be transfferred to the container at the same time.

It is within the scope of the invention that the reaching of the desired predetermined amount of each mixture component is registered by indicating the entry of air into the corresponding connecting hoses.

An apparatus for the use of this special method is characterized in that each of the connecting hoses connected to a storage container is guided through a sensor for the indication of an air content in the corresponding hose and subsequently through a clamping device connected to the sensor and in that the hose connected to the container is guided through a sealing device, which has two sealing points arranged at a distance from each other and an intermediate cutting device and which is connected with the clamping device.

If a storage container is empty and if the connecting hose leading to the hose connection is subsequently filled with air, then this condition is immediately registered by the corresponding, preferably optically acting sensor, and the concomitantly released signal is transferred to the corresponding clamping device. This effects the immediate clamping of the respective hose. The vacuum acting in the vacuum chamber, and transferred to the container to be filled, ceases to act on the corresponding storage container, while the emptying of the additional containers containing the other mixture componenets continues. The described process (i.e. that the sensor arranged with each connecting hose clamps the respective hose when the corresponding storage container is empty and air appears in the hose) continues until the last sensor has been activated.This then activates the downstream sealing device, which mechanically, or de pending on the substance, seals the hose leading to the container to be filled in two places at a distance from one another. At the same time, the hose is cut between the two sealing points. It is useful if this arrangement is turned off at the same time. Having removed the negative pressure in the chamber, it can be opened and the filled container removed. The entire process takes less than two minutes, and is thus essentially faster than any arrangement heretofore known in the state of the art.

It is within the scope of the invention according to the basic principle, to provide the hose connection at the sides facing the container to be filled, with two or more hose connections for the connection of several hoses, each of which is connected to a container. In this specific embodiment, the hose connection is not only connected to two or more storage containers (which would mean that the mixture can comprise two or more individual components), but it can at the same time be connected to more than one container to be filled. Clearly, several containers can be brought to the vacuum chamber at the same time in this embodiment and thus be filled at the same time.It is, on the other hand, in the case of correspondingly smaller vacuum chambers, also possible to bring only one container (i.e. one bag or the like) of all bags connected to the hose connection to the vacuum chamber for filling, while the other bags connected with the hose connection remain outside the vacuum chamber. A positive differential pressure acts on the container to be filled, while a negative differential pressure acts on the containers located outside the chamber. The difference between the two pressures results in only the container located in the vacuum chamber being filled. The desired sealed system for contamination-free filling of pharmaceutical mixtures is maintained in this embodiment as well. The individual bags connected to the system can successively be brought into the chamber and filled.

It has been shown to be disadvantageous if there is an unnecessarily large distance between the sealing device and the bags located in the vacuum chamber. The filling hose, remaining on the container, being sealed at its free end, is often viewed as disturbing in later use. The invention therefore provides for the sealing device to be located inside the vacuum chamber. This results in an extremely short hose length between the sealing device and the bag to be filled. The sealing device can also be arranged on the bottom side of the cover of the vacuum chamber or on the inside of the chamber wall, in any event at a location where the distance to the bag in the chamber is minimal.

The invention is based on the mixture proportions being determined by correspondingly measuring volume in the storage containers.

However, it is also possible to determine the respective weight of the mixture proportions with the total amount being the amount of the total mixture measured according to the weight. In order to Esccmplish this, the indi !í dual mixture components are filled into the container in chronological succession and the reaching of the desired predetermined amount of each mixture component is established by determining the corresponding weight of the container, the corresponding connecting hose is clamped and the connecting hose of the subsequent storage container opened.

An apparatus used for this slightly altered method provides for a scale inside the vacuum chamber, with the container attached to the scale in freely movable fashion and with the scale, as well as the clamping device, whether placed inside or outside the vacuum chamber, connected to a control device used for the preprogramming of the weight of the individual mixture components. In this embodiment, the functional process comprises the individual mixture components being filled in the containers in chronological succession. If the requisite amount of the first mixture portion has been filled into the container, the scale releases a signal which activates the clamping device. When the desired filling level has been reached, the sealing of the connecting hose is also effected, with an amount of liquid still present in the respective storage container.At the same time, the signal released from the scale opens the previously closed clamping device of the subsequent storage container and its mixture components now flow into the container. The described process is repeated until the last storage container, with the last mixture component, has been reached. The guidance of the scale is programmed so that the weights of the individual components of the mixtures are added to one another.

If the last storage container has supplied the desired and intended amount of liquid for the mixture to be prepared, the clamping device is closed and the clamping device, as in the above embodiment, is directed to sealing the hose leading to the container as well as to the cutting device. After having opened the vacuum chamber, the filled container can be removed and labled. Thereafter, the next bag can be brought into the chamber and filled without renewed connection of a new container and the concomitantly-related risk of contamination.

The sealing device of the arrangement according to the invention is especially dependable, and the arrangement can be correspondingly simplified when, as the invention further provides, two operable metal sleeves are pushed onto the hose connected to the container, at a distance from one another corresponding to the distance of the sealing posi tion of the sealing device with the hose having the metal sleeves then being inserted into the sealing device. The hose can thus be clamped easily and reliably in a mechanical fashion by clamping the sleeves. Of course, welding the hose represents an alternative.

Additional characteristics, details and advantages of the invention can be observed in the following description of a few preferred embodiments, as well as from the drawings.

The drawings illustrate: Figure 1 is a first embodiment in schematic representation.

Figure 2 is an enlarged detail of this embodiment.

Figure 3 is a varied embodiment in broken representation.

Figure 4 is an additional embodiment, and Figure 5 is an additional variation of the invention, in schematic representation as well.

In the illustrated embodiment, three storage containers 3, 4 and 5 in their emptying position, i.e. with the sealed opening 6 pointing downwardly, have been hung on a stand 1 or other frame in corresponding holders 2.

A connection hose 7 of suitable cross-section is connected to each of the container seals 6.

In general, these hoses are made of PVC.

These connection hoses 7 are guided past a sensor 9 which addresses the air contained in the hoses 7 in the direction of a hose connection 8. Sensors 9 can, for example, function optically. A clamping device 10 is connected to each sensor 9, which operates magnetically, for example, and, if released by a signal from sensor 9, clamps the respective connecting hose 7, preventing a continued conveyance from the respective storage containers 3, 4, 5.

Hose connection 8 has connection pieces 11, corresponding to the number of connection hoses 7, tightly connecting the hoses 7.

In the embodiment in Figures 1 and 2, a single downstream connection piece 1 2 is provided, which is furthermore tightly connected to the hose 13, leading to the container to be filled, i.e. bag 14. Hose 1 3 terminates at 1 5 at the head of the bag 14.

Container 14 as well as the hose system comprising hose 1 3 and connecting hoses 7, hose connection 8 and connection cannulas 16, form a unit which is produced and packaged in sterile fashion and not removed from the packaging (not illustrated) until ready to use, i.e. for the filling of container 14.

The arrangement furthermore comprises a vacuum chamber 1 8 which is sealed by a hinged cover 1 9 and is connected to the vacuum generator 21 via conduit 20 (not illustrated in detail). In the upper area of wall 22, an airtight inlet for the hose 1 3 leading to container 14 is provided. The vacuum generator 21 has a sealing device 23 through which hose 1 3 is led. Two slightly movable sleeves 24 are pushed onto hose 1 3 in a tightly fitting fashion.As can be seen from Figure 1, these are located in the sealing device 23 in the area of the two sealing points 25 which have corresponding utensils for the deformation of sleeves 24 and thus for the sealing of hose 1 3. Between the two sealing points 25, a cutting knife 26 of abutting device has been arranged in order to separate hose 1 3 between the two sealing points 24.

The embodiment according to Figures 1 and2 operates as follows: The containers 3, 4 and 5 hanging on stand 1 contain the necessary equal or differing amounts of the various mixture components for the pharmaceutical mixture to be prepared. Cannulas 1 6 of connecting hoses 7 are connected to container seals 6 and to the hoses placed into unit 27 which comprises sensors 9 and clamping devices 10 and can also be attached to the stand 1.Then, hose 1 3 arranged downstream from hose connection 8 is placed into the sealing device 23 and the bag 14, arranged at the end of hose 13, is hung onto a hanger 28 on the inside of cover 1 9 of vacuum chamber 1 8. By using the vacuum generator 21, the chamber 18 is placed under negative pressure, and upon opening clamping devices 10, the contents of storage containers 3, 4 and 5 flow through the hose system into the containers 14 to be filled (PVC bags). If the storage containers 3, 4 and 5 contain differing amounts, the corresponding sensor 9 of the connection hose 7 of the storage containers 3, 4 and 5 having the smallest filling amount registers air filling first.

This immediately releases a signal, closing the corresponding clamping device 10, which can be operated, magnetically, for example. Thus, this hose is blocked and no air can enter into container 14. This process is repeated with the remaining storage containers. When the last sensor 9 registers, all clamping devices 10 are closed, and sealing device 23 is re- leased, the sealing points 25 of which seal hose 13, leading to container 14, at two points at a distance from one another. Then, the cutting device 26 cuts the piece of hose situated between the two sealing points. At the same time, the vacuum generator 21 is turned off and vacuum chamber 1 8 ventilated so that cover 1 9 can be opened and container 14 located therein removed, labeled and transferred for further treatment.

The embodiment according to Figure 3 differs from the one just described in that the hose connection 8 has more than one connecting hose on the downstream side. Three connection pieces 1 2 in the illustrated embodiment are each connected to a hose 1 3 leading to a container 14. Two or more than three such connection pieces 1 2 can be provided on hose connection 18. The same applies to connection pieces 11 leading to the storage containers 3, 4 and 5.

In this embodiment, a container 14 to be filled is received in vacuum chamber 1 8 and filled in the manner described above, while the other bags 14 remain outside the vacuum chamber. Due to the various differential pressures, containers 14 outside the vacuum chamber 1 8 remain unfilled, and the liquid only fills container 1 4 inside the vacuum chamber 18. In this manner, a number of containers 1 4 can be successively filled, presuming correspondingly large storage containers 3, 4 and 5 or smaller filling volumes of containers 14, suitable for example for pediatric purposes.

Figure 4 illustrates an embodiment with an electronic scale 30 inside the vacuum chamber 18. It is mounted on the inside of cover 1 9 (which seals chamber 10) and has a hanger 28 to receive container 14 to be filled, which hangs freely in the vacuum chamber 10. Scale 30 is connected to a control device 31 in which the filling systems, corresponding to the programming of the mixture components in the storage containers 3, 4 and 5 are respectively labelled A, B and C. The control unit 31 is additionally connected to unit 27 which comprises sensors 9 and clamping devices 10. In this embodiment, which naturally also can be designed as described in Figure 3, the determination of the component proportions forming the basis of the mixture to be prepared is made according to weight.For this purpose, all clamping devices 10 are closed at the beginning of the filling process.

They are opened, one by one, in order to fill the preprogrammed amount determined by control device 31. As soon as this filling of container 14 has been accomplished, as indicated by scale 30, control device 31 is given a corresponding signal. This in turn addresses unit 27. Thus, the previously opened clamping device 10 is closed and the subsequent one is opened so that the next mixture component can flow into container 14. The weight of the first mixture component is added to the desired weight proportion of the second component in control device 31. If this weight is reached by the corresponding filling of container 14, and indicated by the electronic scale, control device 31 is again addressed and from here, unit 27 or its clamping devices 10. This process continues until all mixture parts have been filled up to the desired amounts. If a storage container 3, 4 or 5 is emptied so that air gets into the connecting hose 7, the corresponding sensor 9 would register and close the connecting hose 7.

The embodiment according to Figure 5 is characterized by the sealing device 23 being arranged inside the vacuum chamber 18. This results in a very short end 32 of hose 1 3 remaining on the bag 14 after cutting hose 13 between the two sealing points 25. This remaining end is no longer disturbing when using container 14 later on.

Claims (11)

1. Method for the preparation of mixtures of pharmaceutical liquids. for example infusion solutions, from at least two storage containers for the individual mixture components, in an arrangement with a vacuum chamber to receive the container to be filled and with a connecting hose for each storage container, as well as a hose connected to the container, which is joined to the connecting hoses of the storage containers via a hose connection, characterized in that, after the reaching of the desired predetermined amount of each mixture component, the connecting hose (7) to the corresponding container (3, 4, 5) is clamped and that, after the clamping of all the existing connecting hoses (7), the hose (13) is closed and cut downstream from the clamping.

2. Method in accordance with claim 1, characterized in that the reaching of the desired predetermined amount of each mixture component is registered by indicating the air intake in the corresponding connecting hoses (7).

3. Method in accordance with claim 1, characterized in that the individual mixture components are successively drawn off into the container and in that the reaching of the desired predetermined amount of each mixture is established by determining the corresponding weight of the container (14), that the corresponding connecting hose (7) is clamped and that the connecting hose (7) of the subsequent storage container is opened.

4. Apparatus for the preparation of mixtures of pharmaceutical liquids, for example infusion solutions, with at least two storage containers for the individual mixture components and a vacuum chamber to receive the container to be filled and with a connecting hose for each storage container, as well as a hose connected to the container, which is joined to the connecting hoses of the storage containers via a hose connection, using the method described in claim 1, characterized in that each connection hose (7) connected to a storage container (3, 4, 5) is guided through a sensor (9) for the indication of air content in the connecting hose (7) and subsequently through a clamping device (10) connected to the sensor (9) and in that the hose (13) connected to the container (14) is guided through a sealing device (23), which has two sealing points (25) arranged at a distance from one another and an intermediate cutting device (26) connected to the clamping device (10).

5. Apparatus for the preparation of mixtures of pharmaceutical liquids, for example infusion solutions, with at least two storage containers for the individual mixture components and a vacuum chamber to receive the container to be filled and with a connecting hose for each storage container, as well as a hose connected to the container, which is joined to the connecting hoses of the storage containers via a hose connection, using the method described in claim 2, characterized in that a scale (30), preferably an electronic scale, is arranged inside the vacuum chamber (18) and that the containers (14) are arranged to be freely movable on it and that the scale (30), as well as the clamping device (10), are connected to a control device (31) for the preprogramming of the weight of the individual mixture components.

6. Apparatus according to claims 3 or 4, characterized in that the hose connection (8) has two or more connection pieces (12) for the connection of several hoses (13), each connected to a container (14).

7. Apparatus according to any of the claims 3 to 5, characterized in that the sealing device (23) is arranged inside the vacuum chamber (18).

8. Apparatus according to any of the claims 3 to 6, characterized in that two flexible metal sleeves (24) are arranged in a formfit fashion on the hose (13) connected to the container (14) at a distance from one another corresponding to the distance of the sealing points (25) of the sealing device (23), and in that the hose (1 3) with the metal sleeves (24) is placed in the sealing device (23).

9. Apparatus according to any of the claims 3 to 7, characterized in that the clamping device (10) has a magnetic drive.

10. Apparatus according to any of the claims 3 to 8, characterized in that the container (14) forms a unit with the hose (hoses) (13), the hose connection (8) and the connecting hoses (7), as well as with their tubes (16).

11. Apparatus according to any of the claims 1 to 9, characterized in that the sealing device (23) has a pneumatic or hydraulic drive.

1 2. Method for the preparation of mixtures of pharmaceutical liquids, substantially as described with reference to Figures 1 and 2, Figure 3, Figure 4 or Figure 5 of the accompanying drawings.

1 3. Apparatus for the preparation of mixtures of pharmaceutical liquids, substantially as hereinbefore described with reference to Figures 1 and 2, Figure 3, Figure 4 or Figure 5 of the accompanying drawings.