EP1417129A1

EP1417129A1 - Method and device for sterilizing containers

Info

Publication number: EP1417129A1
Application number: EP02754336A
Authority: EP
Inventors: Kurt Burger; Guenter Schneider; Thomas Beck; Wolfgang Szczerba; Bernd Wilke; Johannes Rauschnabel; Sascha Henke; Bernd Goetzelmann; Heinrich Van De Loecht; Wolfgang Schmitt
Original assignee: Robert Bosch GmbH
Current assignee: Robert Bosch GmbH
Priority date: 2001-08-08
Filing date: 2002-07-09
Publication date: 2004-05-12
Also published as: WO2003016143A1; JP2004538218A; US20050019209A1; DE10138938A1; US7485258B2

Abstract

The invention relates to a method and a device for sterilizing containers (2). The inventive method is characterized by carrying out, in at least one process step, a plasma treatment in a chamber (5) by inducing an electromagnetic oscillation in such a manner that the plasma (8) is induced in a vacuum close to the areas of the container (2) to be sterilized. The areas of the container (2) to be sterilized are brought closer to the oscillating device (9) between the entry (4) and the exit (6) in the chamber (5) when the container (2) and/or the oscillating device (9) is moved for one or more predetermined intervals in such a manner that a plasma is induced in said areas in the interior and/or exterior of the container. The chamber (5) is provided with a transport device that effects a substantially rotating movement of the container (2) during the transport from the entry (4) to the exit (6) in the chamber (5).

Description

Method and device for the sterilization of containers

State of the art

The invention relates to a method for the sterilization of containers and a device for carrying out the method, starting from the generic features of the main and secondary claims.

It is well known to eliminate harmful microorganisms or germs in containers in medicine or food technology, e.g. in the case of ampoules, septa glasses, syringes, vials or other so-called parenterals packaging or in beverage bottles, physical or chemical processes.

The sterilization of equipment and packaging by the action of dry heat is known for example from WO-9839216 AI or EP 0512244 AI.

Furthermore, in a water vapor method which is known per se with an aqueous pre-cleaning, the containers can be exposed to hot or superheated steam for a predetermined period of time. The duration of the process This requires large systems in order to be able to sterilize large quantities in the production flow. However, this water vapor sterilization is not able to completely remove so-called pyrogenic, ie inflammatory degradation products and cell residue components of killed germs.

The two aforementioned methods have their specific disadvantages. The dry action of heat requires that the equipment to be treated be made of temperature-stable materials, e.g. Steel, ceramics or glass, must be made. In addition, the heat treatment, especially in the area of Parenteralia bottling, must be followed by complex cooling, in particular with regard to energy, space and investment costs, in order to be able to fill temperature-sensitive active substances at room temperature.

Therefore, for sterilization, chemicals such as peracetic acid or hydrogen peroxide in the vapor phase, e.g. known from DE 24 35 037 AI, or gaseous ethylene oxide applied. Although a treatment, for example, with hydrogen peroxide vapor leads to the oxidation of killed cell components, but requires careful cleaning and a correspondingly high cost. In addition, many packaging materials, e.g. many plastics, not stable against hydrogen peroxide. Up to now, both methods can only be applied to glass containers, since the necessary temperatures for plastic containers are too high.

In addition, from DE 25 30 113 AI known methods with UV radiation or according to WO 95 33 651 AI with gamma radiation, have made use of their sterilizing properties and are therefore used in the sterilization of objects and packaging. EP 0 377 799 A1 discloses a method in which a plasma with an electromagnetic radiation having a frequency of about 2.45 GHz is generated for the sterilization of objects. The object is for this purpose completely exposed to a low-pressure plasma and irradiated in an extension with an additional heat source. Sterilization by means of a plasma has hitherto been substantially concentrated on the application in the treatment of medical devices, for example in catheters or transfusion sets.

For the use of objects in medicine, such as. for medical instruments or for the packaging of parenterals, sterilization, ie the depletion of germinant organisms, is not sufficient in the previously described known methods. In addition, it must be ensured here that inflammatory residual components, so-called endotoxins, which are removed from the killed germs, are at least permanently inactivated in their pyrogenic action. This is especially true for the so-called lipopolysaccharides of Gram-negative bacteria, which are located on the outside of the cell wall and, if they enter the bloodstream, can provoke defense reactions.

The requirement of adequate endotoxin depletion via heat requires at least 300 ° C. container temperature and is currently only achieved over a long heat exposure of> 5 minutes, followed by an even longer cooling phase. In the case of plasma sterilization with hydrogen peroxide, the plasma serves only to remove the peroxide residues from the substrates. The sterilizing effect is the conventional chemical action of hydrogen peroxide. The process times are therefore correspondingly long, ie usually greater than 30 minutes. This plasma process thus requires a great deal of time and the use of an aggressive chemical, for example hydrogen peroxide or peracetic acid, which must be completely eliminated before further use of the devices. In addition, special devices are necessary in order to ensure adequate germ and endo-toxin removal even in the interior of the hollow bodies in the case of hollow bodies, as described, for example, in US Pat. No. 5,200,158 A1. Furthermore, from the technical article "RE Peeples and NR Anderson, Journal of Parenteral Science and Technology, Volume 39/1 pages 9-15, 1985" discloses a method in which by means of a microwave coupling a plasma in a vial for the purpose of endotoxin depletion The plasma was ignited with the help of a laser flash and held up for only a few seconds, whereby a large temperature gradient occurred within the vial, eg at the bottom 31 C ° and at the lip 1665 C ° Use of a microwave source and a laser and the unsatisfactory ignition safety, especially with different hollow body formats, and the enormous temperature gradient are particularly disadvantageous for use in packaging technology.

Advantages of the invention

A method for the sterilization of containers or articles, in which the excitation of an electromagnetic oscillation is performed such that a plasma in a vacuum in the vicinity of the sterilized areas of the container is excitable, is according to the invention with the characterizing features of the main claim developed in an advantageous manner. For this the areas of the container to be sterilized between the introduction and the discharge in the chamber are approximated by movement of the container and / or the vibration generating device for one or more predetermined periods such that in these areas inside and / or outside of the container a plasma is excited.

The embodiments of the method according to the invention and the devices which can be constructed for this purpose use the excitation of a high-frequency or microwave plasma in the low-pressure range, or in a vacuum, by guiding the containers to be treated of the type specified at a defined distance for coupling in Microwave field with simultaneous rotation and transport of the container along the plasma source, or a source cascade, to avoid all-round treatment and avoidance of contact contamination. It has a particularly advantageous effect that the transport device is also exposed to the plasma with all surfaces which may come into contact with the container.

Furthermore, it can be achieved in a particularly advantageous manner, the assurance of an extended plasma zone between the container task (infiltration) and the container removal (discharge). All objects, gases or particles must pass through this plasma zone to get from the infiltration to the discharge. This ensures that the sterile filling area in the discharge can not experience carry-over contamination from the infiltration area. The length of the plasma zone also ensures that any local or temporal inhomogeneities of the plasma effect on the surfaces of the container over the treatment time be balanced, with only a corresponding safety margin should be taken into account.

Due to the short process time and the efficiency of the treatment, since only the surface is treated, even the use of plastics as container material is possible. So far, however, was only possible as a container material in most of the known devices because of the use of heat tunneling.

According to one embodiment, a transport device is present in the chamber, which causes a substantially rotating movement of the container during the transport from the introduction to the discharge in the chamber. Advantageously, the plasma source, i. the device for generating the electromagnetic vibrations seen outside of the chamber and from the interior of the chamber this is separated by an arrangement by which a coupling of the electromagnetic oscillations in the chamber to be sterilized areas of the containers and a pressure separation of the vacuum Chamber of the deviating pressure outside the chamber is effected.

According to another advantageous embodiment, a transport device is provided in the chamber, which also causes a substantially rotating movement of the container during transport from the infiltration to the discharge in the chamber. In this case, however, the at least one plasma source is mounted with the device for generating the electromagnetic oscillations within the chamber and separated from the interior of the chamber by an arrangement. By this arrangement, a coupling of the electromagnetic vibrations in the chamber to the sterilized areas of the containers can be effected. The at least one plasma source can thereby be mounted directly in one or more transport rollers for moving and transporting the containers.

The arrangement by which a coupling of the electromagnetic oscillations into the chamber to the regions of the containers to be sterilized takes place can advantageously be a layer of quartz, of oxide ceramics or of Teflon.

The at least one plasma source can be designed, for example, to generate the electromagnetic oscillations in the microwave range. Here, this plasma source is separated from the chamber by a microwave transparent tube or plate. Microwave coupling into the chamber is then effected by a slot discoupling or a horn expansion of a waveguide. On the other hand, the at least one plasma source can also have an electrode for generating the electromagnetic oscillations, with which a capacitive high-frequency coupling can be induced by ion bombardment into the chamber. It is also an advantageous arrangement with a coil, or a worm antenna, applicable, with an inductive Hochfrequenkunginkopplung in the chamber through a corresponding window in the arrangement for separating the plasma source from the chamber is effected. In addition, in the window of the arrangement for separating the plasma source from the chamber, a Faraday shield can be attached, with which the magnetic field can be decoupled at least partially from the electrical effect of the radiated field.

The transport of the container with the device according to the invention can be made according to a first embodiment in a simple manner that the containers during transport in the chamber horizontally in Transport direction lie on at least two transport rollers, which are driven in such a way around a likewise horizontally lying in the direction of transport axis of rotation. In this case, the containers can be rotated past the coupling region of the plasma source and transported at the same time.

In a second embodiment, the containers are in the chamber during transport in a rotating tube, in the middle or around which at least one plasma source is arranged. The tube is driven about an axis of rotation lying horizontally in the transport direction in such a way that the containers can be rotated past the coupling region of the plasma source and simultaneously transported.

According to a third embodiment, the containers lie during transport in the chamber on an inclined plane, so that the containers roll about an axis of rotation transversely to the transport direction and the containers are vorbeidrehbar past the Einkopplungsbereich of the plasma source and simultaneously transportable.

Furthermore, a fourth embodiment is advantageous in which the containers lie during transport in the chamber on at least one roller with a worm gear, which is driven about a horizontally lying in the transport direction rotation axis such that the containers on the coupling region of the plasma source vorbeidrehbar and simultaneously are transportable. In a modification of this embodiment, vertically arranged, rotating rollers may be arranged as worm drive, which transport the containers in their midst. The containers can be transported in a particularly advantageous manner with their opening facing down through the plasma. With a fifth embodiment, it can be achieved that the containers lie during transport in the chamber in a device which can be moved in the transport direction and which consists of rollers which can be rotated transversely to the transport direction and between which the containers come to lie. The containers, which roll during the movement of the device in the transport direction about an axis of rotation transversely to the transport direction, are guided in such a way that the containers can be pre-rotated and simultaneously transported at the coupling region of the plasma source. The rotational movement of the rollers can be done in a simple manner by a chain or tooth drive on which the device is movable and engage in the corresponding teeth of the rollers. It is also advantageous if at least one further plasma source is arranged below and / or laterally next to the chamber, with which a sterilization of the transport device and / or containers dropped by the transport device can be carried out. In addition, the method according to the invention can be advantageously improved by determining the sterilizing effectiveness of the plasma by measuring the light emission, in particular with regard to the occurrence, the duration and the spectral components of the light.

drawing

Embodiments of devices for carrying out the method according to the invention for the sterilization of containers will be explained with reference to the drawing. Show it: FIG. 1 shows a schematic view of a device with a transport device arranged in a low-pressure or vacuum chamber for passing through the containers to be sterilized, wherein a plasma is excited in the chamber,

2 shows a section through the transport device according to FIG. 1 with two rollers, FIG.

FIG. 3 shows a circuit diagram for excitation of the plasma with a high-frequency capacitive coupling of the electromagnetic field,

FIG. 4 shows a circuit diagram for excitation of the plasma with a high-frequency inductive coupling of the electromagnetic field,

5 shows a modification of the arrangement according to FIG. 5 with a Faraday shield, FIG.

FIG. 6 shows a schematic view of an embodiment of a transport device in which the containers are moved in a rotating tube in the middle of which the plasma source is arranged,

FIG. 7 shows a cross section through the arrangement according to FIG. 6,

8 shows a schematic view of an exemplary embodiment of a transport device in which the containers move on an inclined plane, FIG.

9 is a schematic view of an embodiment of a transport device in which the loading conditions are moved by a worm drive,

FIG. 10 shows a schematic view of an exemplary embodiment of a transport device in which the containers are moved by a chain transport device,

Figure 11 is a plan view of the chain transport device of Figure 10 and

Figure 12 is a schematic view of a device with one of the aforementioned transport devices, wherein in the chamber a plasma is excited by two opposing plasma sources.

Description of the embodiments

1 shows a first embodiment of a device 1 is shown, are introduced with the containers 2 in an unsterile region 3 of the device 1. The containers 2 are then transported through a first lock 4 into a low-pressure or vacuum chamber 5 with a mechanical arrangement, which is not described here, and move there by means of a transport device described in greater detail below in the direction of a second lock 6 for removal into a sterile area 7 the device 1, from which they can then be removed.

FIG. 1 shows the generation of a plasma 8 in the chamber 5 through the field of a microwave transmitter as a plasma source, this being schematically indicated by arrows 9. FIG. 2 shows the first embodiment of 1, in which the containers 2 are rotated during transport from the lock 4 to the lock 6 by means of rollers or rollers 10 and 11, so that all areas of the containers 2 in the same way to the plasma 8 are exposed.

The two transport rollers 10 and 11 according to FIG. 2 can be slightly inclined in order to overcome the distance between the locks 4 and 6 by means of gravity. Due to the constant rotation of the containers 2, the friction is minimized.

An example of a plasma source is a line source which coaxially conveys the microwave radiation into a vacuum, a quartz tube defining the boundary between the vacuum and the internal normal pressure and inside a concentrically arranged metal rod acting as an inner conductor. The plasma, which is excited on the outside of the quartz tube, serves as an outer conductor. This principle can be operated cascaded with an array of the mentioned line sources in order to form a planar plasma. The microwave arrangement is usually operated at frequencies of 300 MHz to 30 GHz.

Furthermore, a quartz plate is applicable instead of the quartz tube. Instead of quartz as a tube or plate material, other microwave permeable materials, such as e.g. Oxide ceramics or Teflon be applied. It is also possible, by means of a slot extraction or a Hornaufweitung a waveguide to couple the microwave radiation surface in the vacuum.

In this context, with reference to the transport device according to Figures 1 and 2 instead of the two horizontally rotating transport rollers 10 and 11 of any material and rotating quartz tubes with a Copper rod can be used inside, so that the rollers 10 and 11 so the actual plasma sources would be.

The principal mode of action of the plasma sterilization with the proposed arrangement is explained below.

In the field of coupling the high-frequency or microwave radiation, here plasma source 9 of Figure 1, the field strength is greatest and can be stimulated here also the easiest. However, as an electrical conductor, the plasma can also be shielded by the fact that radiation can be absorbed and removed; Thus, further propagation of the radiation is prevented or at least mitigated.

As a result of the minimal removal of the container 2 for the purpose of being coupled in by the plasma source 9, a so-called dense plasma between the coupling and the container 2 is avoided in the exemplary embodiment described here. Therefore, a sufficient part of the radiated power is also in the interior of the container 2 in order to stimulate a plasma 8 there as well. The distance between the wall of the container 2 and the coupling can therefore be chosen so that either only inside or at least predominantly inside, only outside at a great distance or inside and outside a plasma is applied simultaneously. If multiple plasma sources 9 are used, complete treatment of all wall regions of the container 2 could be achieved successively or simultaneously at the same time.

FIG. 3 shows a capacitive high-frequency coupling (RF) for plasma generation for electromagnetic waves of approximately 10 kHz to 27 MHz. The coupling takes place between an electrode 20 and a counter electrode 21, which may be the grounded housing of the vacuum chamber 5, to ground, wherein the electrode 20 has a high Ion bombardment can ensure, if this electrode 20 has a smaller area in relation to the much larger area of the counter electrode 21.

An inductive high-frequency coupling by a coil as a worm antenna 22 can be seen from FIG. This screw antenna 22 is in atmospheric pressure and is mounted above a quartz or Teflon window 23 in the chamber 5, which separates the chamber interior under vacuum from the outside under normal or atmospheric pressure.

FIG. 5 shows an inductive high-frequency coupling, as shown in FIG. 4, with additional introduction of a so-called Faraday shield 23, which contributes to decoupling the magnetic from the electrical effect of the irradiated field.

In the following embodiments are still different ways of transporting the containers 2 are given with simultaneous rotation in the device 1. In the embodiment of Figure 6 and Figure 7, the containers 2 are in a nearly horizontal or slightly inclined rotating tube 24, in the middle, for example, a quartz tube 12, as described with reference to Figure 2, is placed. Alternatively, one or more plasma sources may also be arranged around the rotating tube 24, in which case the tube 24 is made of quartz or Teflon.

FIG. 8 shows an exemplary embodiment in which the containers 2 are unrolled on an inclined plane 25. By gravity, the transverse to the transport direction 26 containers 2 are set in rotation about its longitudinal axis. In an embodiment according to Figure 9, the two horizontally arranged rollers 27 and 28 (see rollers 10 and 11 of Figure 2) have a thread or a thread-shaped applied zone with a higher friction coefficient to the rest of the surface of the roller and act as a worm drive so that the containers 2 can be transported in a defined manner from the lock 4 to the lock 6. It may also be sufficient to provide only one roller with such a thread structure and to use the second roller without thread structure as an abutment, possibly with a low coefficient of friction of its surface.

The rolls with the thread 27 and 28 according to FIG. 9 can also be made vertical or almost vertical, if e.g. is ensured by a third roller or a plate with a low coefficient of friction of the surface that the containers 2 do not fall out of the guide. In this case, it is also possible that the containers 2 can be transported with their opening down. As a plate can also be the coupling window of the electric field that is mounted to excite a plasma in a vacuum.

The containers can be transported according to Figure 10 and 11 on rollers 32 which are driven on a chain 33 via a gear drive. The chain links are designed so that the containers 2 lying on them are set in rotation about their longitudinal axis.

In order to achieve even more reliable sterilization of the previously described transport devices, according to FIG. 12, one or more additional plasma sources 34, 35 can be placed below or next to the transport device, here for example according to FIG. The plasma source 35 under the transport device could do so be used, possibly from the treatment area falling down containers 2, or other objects, parts or particles also to sterilize.

Claims

claims

1) Method for the sterilization of containers (2), in which

- In at least one step in a chamber (5) a plasma treatment by excitation of an electromagnetic oscillation is performed such that the plasma (8) is excited in a vacuum in the vicinity of the areas of the container to be sterilized (2), characterized that

the areas of the container (2) to be sterilized between the sluice (4) and the discharge (6) in the chamber (5) with constant movement of the container (2) and / or the vibration generating device (9) for one or more predetermined periods are approximated to the vibration generating device (9), that in these areas inside and / or outside of the container, a plasma (8) is excited. 2) Method according to claim 1, characterized in that

the plasma treatment is sterilization and / or depyrogenation.

3) Method according to claim 1 or 2, characterized in that with a measurement of the light emission, in particular with regard to the occurrence, the duration and the spectral components of the light, the sterilizing efficiency of the plasma (8) is determined.

4) Device for carrying out the method according to one of the preceding claims, characterized in that

in the chamber (5) a transport device is provided, which causes a substantially rotating movement of the container (2) during transport from the inflow (4) to the discharge (6) in the chamber (5) and that

the plasma source (9) with the device for generating the electromagnetic oscillations is mounted on the outside of the chamber (5) and is separated from the interior of the chamber (5) by an arrangement by which a coupling of the electromagnetic oscillations into the chamber (5 ) to the sterilized areas of the containers (2) and a pressure separation of the vacuum of the chamber (5) from the deviating pressure outside the chamber (5) is effected. 5) Device for carrying out the method according to one of the preceding claims, characterized in that

the at least one plasma source (9) is mounted with the device for generating the electromagnetic oscillations within the chamber (5), which in turn is subdivided and the plasma source (9) is separated from the treatment chamber of the chamber (5) by this subdivision in that, nevertheless, an electromagnetic field can be coupled into the container or containers (2).

6) Device according to claim 5, characterized in that

- The at least one plasma source in one or more transport rollers (10,11) is mounted for movement and transport of the containers.

7) Device according to claim 5 or 6, characterized in that

the arrangement by which the electromagnetic oscillations are coupled into the chamber to the regions of the containers to be sterilized is a layer or other arrangement of quartz, oxide ceramic or Teflon. 8) Device according to one of claims 4 to 7, characterized in that

the at least one plasma source for generating the electromagnetic oscillations in the microwave range is separated from the chamber by a tube or plate permeable to microwaves, and in that

a Mikrowelleneinkopplung in the chamber by a slotted decoupling or from a Hornaufweitung a waveguide is effected.

9) Device according to one of claims 4 to 7, characterized in that

the at least one plasma source for generating the electromagnetic oscillations is an electrode with which a capacitive high-frequency coupling can be effected by ion bombardment into the chamber.

10) Device according to one of claims 4 to 7, characterized in that

the at least one plasma source for generating the electromagnetic oscillations is a coil with which an inductive high-frequency coupling into the chamber can be effected by a corresponding window in the arrangement for separating the plasma source from the chamber.

11) Apparatus according to claim 10, characterized in that in the window of the arrangement for separating the plasma source from the chamber, a Faraday plate is mounted, with which at least partially the magnetic of the electrical effect of the irradiated field can be decoupled.

12) Device according to one of claims 4 to 11, characterized in that the containers are horizontal during transport in the chamber in the transport direction on at least two transport rollers which are driven about a likewise horizontally lying in the transport direction of rotation axis such that the containers at the coupling region The plasma source can be rotated past and transported at the same time.

13) Device according to one of claims 4 to 11, characterized in that

the containers lie in a rotating tube during transport in the chamber, in the middle or around which the at least one plasma source is arranged and the tube is driven about a horizontal axis of rotation in the direction of transport such that the containers are at the coupling region of the plasma source are rotatable and transportable at the same time.

1H) Device according to one of claims 4 to 11, characterized in that the containers lie on an inclined plane during transport in the chamber, so that the containers roll around a rotation axis transversely to the transport direction, so that the containers are rotatable past the Einkopplungsbereich of the plasma source and simultaneously transported.

15) Device according to one of claims 4 to 11, characterized in that

- The containers during transport in the chamber on or on at least one roller with a screw thread or other thread-shaped structure higher friction are ben driven around a horizontally lying in the transport direction axis of rotation such that the containers on the coupling region of the plasma source vorbeidrehbar and are simultaneously transportable.

16) Device according to one of claims 4 to 11, characterized in that

the containers are during transport in the chamber on a movable device in the transport direction, which consists of transversely to the direction of transport rotatable rollers and between which the containers come to rest, and that

- The containers, during the movement of the device in the transport direction, about a rotational axis transverse to

Roll transport direction, so that the containers on

Einkopplungsbereich the plasma source vorbedrehbar and are simultaneously transportable. lϊ) Apparatus according to claim 16, characterized in that

the rotational movement of the rollers is effected by a chain or tooth drive on which the device is movable and engage in the corresponding teeth of the rollers.

18) Device according to one of claims 4 to 1 ?, characterized in that

at least one further plasma source is arranged below and / or laterally of the chamber, with which a sterilization of the transport device and / or containers (29) dropped by the transport device can be carried out.