DE10045585A1 - Process for sterilizing and depyrogenizing washed containers - Google Patents

Abstract

The invention relates to a method for sterilising and depyrogenating washed containers. According to the invention, depyrogeneration takes place after sterilisation in a separate operational step. Preferably, sterilisation is carried out by condensating a mixture containing steam and hydrogen peroxide steam. In order to depyrogenate, preferably a low pressure plasma is used. Before sterilisation, the containers are freed from eventual residual moisture, for example by means of microwave irradiation.

Description

The invention relates to a method for sterilizing and depyrogenizing washed containers.

Sterilizing is the release of an object from reproductive organisms. This Demand is met by killing all microorganisms. This does not include only the vegetative cells, but also the permanent forms and especially the particular ones resistant bacterial endospores.

Containers to be sterilized, for example in the pharmaceutical industry or at Beverage filling are used and which usually consist of glass or plastic, must be cleaned in a wash before sterilization. These containers pass through a washing machine before they, with a small amount of residual water, enter the Sterilization system.

In the water that is applied to the surfaces of the containers when they are washed, there are always bacterial endotoxins, so-called lipopolysaccharides. These are Cell membrane components of so-called gram-negative bacteria and are released when this die and disintegrate into their cell components. The lipopolysaccharides come into the Bloodstream, so they produce a fever. The lipopolysaccharides must therefore be inactivated Process commonly referred to as depyrogenization.

In practice, depyrogenization usually takes place through treatment in a dry place Heat at about 300 ° C instead. Because this temperature and the length of stay also for sterilization sterilization and depyrogenization are usually suitable in one  carried out joint operation. This, in itself, rational method has the Disadvantage that for the two process steps not necessarily the optimal methods be used. This is especially true when it would be desirable to have containers, for example made of plastic, to sterilize at lower temperatures.

The invention is based on the object of sterilizing and depyrogenizing washed Make containers more variable.

The object is achieved in that the depyrogenization after sterilization in one separate operation is carried out.

The separation of the two work steps against the usual practice makes it possible choose the optimal method for each of the two processes. In particular, this does not exist more the need to carry out sterilization under high thermal loads.

In an embodiment of the invention, depyrogenization is carried out by the action of plasma, because suitable plasma gases are able to, by electron and ion bombardment as well as by chemical reaction to inactivate the lipopolysaccharides. This ignites the plasma a high-frequency generator connected, the high-frequency power can be inductive or can be capacitively coupled, for example with an approved frequency of 13.56 MHz is working.

A low-pressure plasma is advantageously used for the depyrogenation. This has the advantage that a "cold" plasma can be generated, thereby preventing the containers to be depyrogenized or only be exposed to low thermal loads.

A gas is to be used as the plasma gas which is used for depyrogenization in the plasma phase suitable is. This is the case with oxygen, for example, in the maximum possible concentration is enriched with ozone. However, the gas mixture must be Sterile filters are carried, since it is not a sterile gas by nature and because the containers to be depyrogenized already through the previous sterilization process have been made germ-free and, of course, must not be recontaminated. If necessary, a gas mixture can be used, which with another component increases the effect of the ozone-oxygen plasma.  

To simplify the apparatus, it can advantageously be provided that the sterilizing and depyrogenization at intervals in a common treatment chamber is carried out. However, this is not a mandatory requirement.

By separating the process steps of sterilizing and depyrogenizing can now the sterilization, depending on the application, can be carried out in an optimal manner, for example by condensing a water vapor and hydrogen peroxide vapor containing Steam mixture on the surfaces of the containers. When sterilizing using Hydrogen peroxide, which is always present in aqueous solution, is the actual one Kill germs purely chemically, through the action of "activated" hydrogen peroxide. The one here The used term "activate" is undefined, but takes place by suitable heat supply on Hydrogen peroxide is a chemical and / or physical change that ultimately takes place Germ killing causes. Such "activation" of the hydrogen peroxide takes place in one Condensation instead, exactly when it is actually needed for sterilization.

In one embodiment of the invention, the steam mixture is generated in an evaporator and then passed into a treatment chamber, the chamber pressure well below the Vapor pressure of the steam mixture is. Due to the negative pressure in the treatment chamber the vapor mixture to be condensed arrives even without any carrier gas medium all surfaces to be sterilized and wet them with a thin, homogeneous surface Liquid film. A microscopic thinner is almost sufficient for this, almost to the naked eye invisible condensate coating.

The vapor mixture condensed onto the surfaces of the containers to be sterilized can by evacuating to a pressure below the boiling point of water and hydrogen peroxide can be easily removed from the treatment chamber. It is therefore neither an afterthought Cleaning requires subsequent heating to evaporate the condensate.

Residual amounts of water, as mentioned at the beginning, due to the washing process on the containers can adhere, may hinder effective sterilization because the condensate not fast enough or under certain circumstances not at the surfaces to be sterilized or germs contained in the liquid can reach. It is therefore in a further embodiment Invention provided that the washed containers may be sterilized before existing residual moisture can be freed. As a result, the surfaces to be sterilized  the container is placed in a condition that allows effective sterilization by condensation of the steam mixture consisting of water and hydrogen peroxide.

It is particularly advantageous if the removal of the residual moisture by means of drying Microwave radiation is carried out. So that the existing microwave energy is effective is used, the chamber in which the microwave radiation occurs, evacuated. This allows the water to be evaporated, for example, at a temperature of 60 ° C already reach its boiling point. It is possible to get rid of the To carry out residual moisture in the same treatment chamber in which the sterilization takes place. This makes the equipment easier, for example by having one and the same Vacuum pump can be used for the different process steps.

It does not matter whether you work with one or more treatment chambers Applicant considered the most advantageous process steps in combination an exemption the container of residual moisture by microwave radiation, sterilization by Condensing a water vapor and hydrogen peroxide vapor containing Vapor mixture on the surfaces of the containers and depyrogenation by means of a Low-pressure plasma.

Further advantages and features of the invention result from the following description some embodiments.

Show it:

Fig. 1 is a block diagram for explaining the process steps according to the invention,

Fig. 2 shows a schematic representation of a preferred embodiment of the invention.

According to the schematic illustration of FIG. 1 1 through the tank 2 a washing machine, a drying chamber 3, a sterilization chamber 4, a Depyrogenisierungskammer 5, and subsequently a filling station 6 and a closing. 7 The sterilization in the sterilization chamber 4 and the depyrogenization in the depyrogenization chamber 5 takes place according to the invention in separate work steps.

As indicated by arrows, drying is supported by microwave radiation 8 , sterilization by reaction gas supply 9 and depyrogenation by plasma gas supply 10 . A steam mixture of water vapor and hydrogen peroxide vapor can be used as the reaction gas for the sterilization.

The drying chamber 3 , the sterilization chamber 4 and the depyrogenization chamber 5 are connected to a vacuum pump (not shown) via a common vacuum connection 11 .

As indicated by a dash-dotted rectangle, the drying chamber 3 , the sterilization chamber 4 and the depyrogenization chamber 5 can alternatively be combined to form a common treatment chamber 12 , but the process steps of drying, sterilizing and depyrogenizing are carried out at time intervals.

Such a common treatment chamber 12 , which is grounded, is shown schematically in FIG. 2. One can see the already washed containers 1 , which consist for example of glass or plastic and of which a large number is arranged in the treatment chamber 12 . The direction of transport through the treatment chamber 12 runs from the viewer to the drawing level, the treatment chamber 12 being provided with an inlet and outlet openings (not shown) and corresponding locks.

The individual containers 1 are placed in the treatment chamber 12 on a grating 13 . The treatment chamber 12 is connected to a vacuum pump 15 via a vacuum line 14 and a valve 16 . This can be designed for a vacuum below a Pa.

In a first process step, the containers 1 are freed of any residual moisture by a drying process. A microwave generator 17 , which operates at, for example, 2.45 GHz or another suitable frequency, is used for this. The power of the microwave is radiated in the present case, as an example, via a waveguide 18 . In the area of the treatment chamber 12 , the waveguide 18 , which is rectangular in cross section, is widened to form an antenna 19 which is closed off from the treatment chamber 12 by a microwave-transparent window 20 made of quartz glass, for example. The window 20 must be mechanically very stable, since there is negative pressure in the treatment chamber 12 , but there is atmospheric pressure in the antenna 19 and the waveguide 18 .

To match the impedance of the loaded treatment chamber 12 to the wave resistance of the waveguide 18 , an impedance converter 21 is provided, for example a three-screw transformer. To protect the microwave generator 17 in the event of a mismatch, a so-called isolator 22 is attached between the impedance converter 21 and the microwave generator 17 and branches off the reflected wave, for example, into a water load, ie into a water-cooled resistor that has the same wave resistance as the waveguide 18 .

Standing waves can arise when the microwave causing the drying is irradiated into the treatment chamber 12 . This results in places where the field strength and thus the power input reaches a maximum value over time, but also places where the power input is almost zero on average. Containers 1 , which are located at such nodes during the drying process, can be brought into areas in which a power input takes place by moving the grating 13 . Since the wavelength is about 12 cm, the distance between two nodes is about 6 cm. It would therefore be optimal to move the container 1 during the drying period by 6 cm in each spatial direction. Therefore, for the purpose of approximation to this ideal condition the grate 13 are assigned, drive axles 23 and 24, which are connected via crank lever 25 with the grid. 13 The angle levers 24 execute an oscillating circular movement in accordance with the direction of the double arrows, the drive axes 23 and 24 optionally being able to additionally oscillate in their axial direction.

After switching off the microwave generator 17 , the next process step takes place with the subsequent sterilization of the containers 1 . For this purpose, a steam mixture of water vapor and hydrogen peroxide vapor is first generated, it being basically irrelevant whether the steam in question is wet steam or superheated steam. The evaporator or carburetor, the design of which is basically arbitrary, is provided with the reference number 26 . An aqueous solution of hydrogen peroxide with the desired concentration is fed to the evaporator 26 via a feed line 27 and a valve 28 in the direction of the arrow. The evaporator 26 is arranged upstream of the treatment chamber 12 , in which the containers 1 to be sterilized and which have meanwhile dried are located.

As with microwave drying, the treatment chamber 12 is also evacuated in the desired manner for sterilization. The treatment chamber 12 is then isolated from the vacuum pump 15 by closing a valve 16 , so that suction is no longer carried out.

By opening a valve 29 , care is now taken to ensure that the vapor mixture in the evaporator 26 reaches the treatment chamber 12 via the line 30 , preferably by adiabatic expansion. The pressure in the evaporator 26 must therefore be higher than the chamber pressure in the treatment chamber 12 . During the expansion, the volume occupied by the steam mixture increases, as a result of which the steam mixture cools significantly below the dew point and condenses on all accessible surfaces of the container 1 and the grating 13 and the inner walls of the treatment chamber 12 . The pressure in the treatment chamber 12 rises again. After a predetermined time of the vacuum pump 15 is drawn off the condensate by means of the treatment chamber and vented 12 via a supply line 31 and a valve 32 with sterile purge gas.

Depyrogenization then takes place in a further step. This is done with the aid of a low-pressure plasma with the treatment chamber 12 likewise being evacuated.

Via a feed line 33 , plasma gas to be ionized can be introduced into the evacuated treatment chamber 12 , preferably oxygen enriched with ozone. A throttle valve 34 regulates the inflow of the plasma gas. A gas container 35 is provided for the plasma gas itself. So that the already sterilized containers 1 are not recontaminated, the feed line 33 is connected to the treatment chamber 12 via a sterile filter 36 .

A high-frequency generator 37 of, for example, 13.56 MHz or another approved frequency is used to ignite the low-pressure plasma required for the depyrogenation. The high-frequency generator 37 generates an alternating voltage, which is transmitted to the plasma to be formed by an adaptation network 38 , a so-called matchbox. The matching network 38 serves the purpose of matching the impedance of the load to the characteristic impedance of the high-frequency generator 37 . Two identical electrodes 39 and 40 are located within the treatment chamber 12 .

It is important that the electrodes 39 and 40 in the form of plates are electrically insulated from the plasma, which can be done, for example, by a coating that withstands the action of the plasma. This insulation ensures that, on average over time, no direct current can flow through the electrodes 39 and 40 , which would result in an ohmic loss in the electrode edge layer. Preferably, neither of the two electrodes 39 and 40 should be at the same electrical potential as the metallic treatment chamber 12 . Rather, a symmetrical structure should be selected in which the two electrodes 39 and 40 are galvanically separated from the ground potential via a transformer contained in the matching network 38 . Both electrodes 39 and 40 are then equal to the potential of the metallic wall of the treatment chamber 12 , which is expressed in a largely symmetrical plasma geometry.

Claims (12)

1. A method for sterilizing and depyrogenizing washed containers, characterized in that the depyrogenizing is carried out after the sterilization in a separate operation. 2. The method according to claim 1, characterized in that the depyrogenization by Plasma exposure is carried out. 3. The method according to claim 2, characterized in that for depyrogenization Low pressure plasma is used. 4. The method according to claim 2 or 3, characterized in that for generating the plasma a gas mixture containing ozone is used. 5. The method according to claim 4, characterized in that the gas mixture by a Sterile filter is made sterile. 6. The method according to any one of claims 1 to 5, characterized in that the sterilization and the depyrogenization at intervals in a common treatment chamber is carried out. 7. The method according to any one of claims 1 to 6, characterized in that the sterilization by condensing a water vapor and hydrogen peroxide vapor containing Vapor mixture is carried out on the surfaces of the containers. 8. The method according to claim 7, characterized in that the steam mixture in one Evaporator generated and then into a treatment chamber without transport gas flow is directed, the chamber pressure well below the vapor pressure of the steam mixture in the Evaporator lies. 9. The method according to claim 7 or 8, characterized in that the condensed Vapor mixture by evacuating to a pressure below the boiling point of water and Hydrogen peroxide is removed from the treatment chamber.   10. The method according to any one of claims 1 to 9, characterized in that the washed container should be cleaned of any residual moisture before sterilization become. 11. The method according to claim 10, characterized in that the exemption from the Residual moisture is carried out by microwave radiation. 12. The method according to claim 10 or 11, characterized in that the exemption from the Residual moisture is carried out in the same treatment chamber in which the Sterilization takes place.