METHOD FOR REDUCING MICROBIOLOGICAL CONTAMINATION

Abstract

A method for reducing microbiological contamination in a closed chamber (6), formed by at least two interconnected components (1, 4), by introducing a germicidal medium into the chamber (6).

Claims

1. A method for reducing microbiological contamination in a closed chamber (6), formed by at least two interconnected components (1, 4), by introducing a germicidal medium into the chamber (6).

2. The method according to claim 1, characterized in that the medium inside the chamber (6) is exposed to the effects of an energy source.

3. The method according to claim 1, characterized in that a germicidal fluid, preferably in liquid form, is introduced into the chamber (6) as the medium.

4. The method according to claim 1, characterized in that the fluid at least partially changes from the liquid phase to the gaseous phase, preferably transitions to the gaseous phase due to heating by means of an energy source.

5. The method according to claim 1, characterized in that the fluid in the chamber (6) is at least partially vaporized and condensed at least once, preferably vaporized and recondensed several times.

6. The method according to claim 1, characterized in that the energy for heating is introduced in the form of radiation, preferably in the form of radiation pulses.

7. The method according to claim 1, characterized in that the radiation essentially only directly heats the fluid.

8. The method according to claim 1, characterized in that the fluid is at least partially chemically modified and/or degraded during its residence time in the chamber (6).

9. The method according to claim 1, characterized in that the fluid is held in the chamber (6) for a residence time, during which the concentration of the fluid and/or its degradation products can be at least a partially reduced by permeation out of the chamber (6).

10. The method according to claim 1, characterized in that the course of the change in the concentration of the fluid and/or its degradation products in the chamber (6) is tracked using non-destructive, preferably spectroscopic methods.

11. The method according to claim 1, characterized in that the fluid is evaporated by means of dielectric heating using radio waves in the frequency range of 5 MHz to 50 MHz.

12. The method according to claim 1, characterized in that evaporation of the fluid is effected by dielectric heating using microwaves in the frequency range of 500 MHz to 30 GHz, preferably having frequencies of 915 MHz or 2450 MHz or 5800 MHz.

13. The method according to claim 1, characterized in that a solution containing chlorine, ozone or a peroxide, preferably hydrogen peroxide, is provided as the fluid.

14. The method according to claim 1, characterized in that a solution containing water and/or at least one alcohol, preferably water and ethanol, as a solvent is provided as the fluid.

15. The method according to claim 1, characterized in that an antiseptic is provided as the fluid, which preferably contains at least one alcoholic active substance, particularly preferably ethanol and/or isopropanol.

16. The method according to claim 1, characterized in that a cap (4) and the head (2) of a container (1), preferably a filled container (1) for medical purposes, are provided as the components forming the chamber (6).

17. The method according to claim 1, characterized in that the components (2, 4) are essentially formed from at least one plastic, preferably polyolefin, particularly preferably polypropylene and/or polyethylene.

18. The method according to claim 1, characterized in that the filled container (1) is produced using the BFS process.

19. The method according to claim 1, characterized in that the filled container (1) has a head membrane (8) having at least one depression.

20. The method according to claim 1, characterized in that the filled container (1) is a multilayer container, preferably having at least one layer containing an ethylene-vinyl alcohol copolymer or a cycloolefin polymer or cycloolefin copolymer.

Description

[0018] The invention is explained in detail with reference to the drawings below. In the drawings:

[0019] FIG. 1 shows a perspective oblique view of a partial representation of a state-of-the-art infusion container, to the neck collar of which a cap can be attached;

[0020] FIG. 2 shows a simplified longitudinal section of a cap that can be attached to the container of FIG. 1; and

[0021] FIG. 3 shows in simplified longitudinal section the neck collar of the container of FIG. 1 with the cap of FIG. 2 attached.

[0022] The method of chemical sterilization according to the invention is explained with reference to the attached drawing, using an infusion bottle made of plastic having a tightly attached plastic cap and manufactured according to the BFS process known per se by way of example, wherein an aqueous is hydrogen peroxide solution is provided as the germicidal medium. In a analogous way, the invention can also be applied to other container systems mentioned above and using other solvents, germicidal agents, such as known disinfectants (antiseptics), which are also mentioned above. The container denoted by the numeral 1 and shown in FIG. 1, which is manufactured and filled according to the BFS process, has a neck collar 2 at the container neck 3 and above it a head membrane 8 forming the tight container closure and which can be perforated for an infusion process, as described in DIN ISO 15759.

[0023] FIG. 2 shows a cap 4, made of a rigid plastic material and also is formed according to DIN ISO 15759 and, as shown in FIG. 3, that can be tightly welded to the neck collar 2 of the container 1 at the cap edge along a welding point 7, for instance by means of hot plate welding. The cap 4 could also be tightly connected to the container 1 by over molding. As shown in FIGS. 2 and 3, elastomeric elements 5 sealing the system during use are located at the opening areas of the top of the cap 4 at points that can be pierced by a cannula or spike for an infusion procedure. The elastomeric elements 5 are, as described for instance in the application DE 10 2017 000 048.4, which shows a post-published state of the art, made of an elastomer, which is suitable for being cohesively welded to the material of the cap 4. FIG. 3 shows a chamber 6 closed up in a sealed manner in the cap 4, when the latter is connected to the neck collar 2, which chamber extends along the inside of the circular cylindrical side wall 10 of the cap 4 and along the head membrane 8 and forms an interstice of relatively small volume, which is chemically sterilized by the method according to the invention.

[0024] For this purpose, in the example of the method to be described here, a small volume (approx. 0.01 ml to 0.3 ml) of an aqueous hydrogen peroxide solution is metered onto the head membrane 8, for instance by dropping or spraying, and then the cap 8 is sealingly connected to the neck collar 2 so that the chamber 6 is closed in a sealed manner. Alternatively, the fluid can also be sprayed onto the inner surfaces of the cap 4. Direct heating of the applied fluid is achieved by microwave radiation. This has the advantage of heating the fluid directly, while the walls of chamber 6 are warmed only slightly, if at all, such that the radiation itself contributes only indirectly to the reduction of the germ count. At a preferred frequency of microwave radiation in a frequency range of 500 MHz to 30 GHz, the fluid is at least partially evaporated and thus distributed homogeneously inside the chamber 6. Due to the increase in volume during evaporation, this results in an overpressure in chamber 6 and thus to the pressure-induced overheating of the hydrogen peroxide. On the one hand, this initiates the chemical decomposition of the hydrogen peroxide into the harmless substances water and oxygen, on the other hand, even surfaces that are difficult to access, such as undercuts, gaps, channels and the like, are reliably reached.

[0025] Advantageously, microwave pulses are used, which result in a pulsating continuous, at least partial evaporation and repeated micro-condensation of the hydrogen peroxide, a preferred type of condensation, in which extremely small droplets, not visible to the naked eye, are generated. This is also where the thermal break-down of the hydrogen peroxide to water and oxygen sets in. In contrast thereto, in the known methods of sterilizing insulators using gaseous hydrogen peroxide, care must be taken to prevent break-down from occurring in the vaporizer.

[0026] An advantage of the method according to the invention is also no carrier gas being required to transport the gaseous hydrogen peroxide, but generating gaseous hydrogen peroxide directly in the chamber 6 to be sterilized and at least partially degrading it there. It was also found that even sensitive filling products present in the container 1 were not measurably affected. It is assumed that the hydrogen peroxide is already broken-down to a large extent before there is any noticeable permeation into the filling product. Due to the low adsorption and permeation of hydrogen peroxide to and into polyolefins, especially to low-density polyethylenes, such container materials are preferable. As described in DE 103 47 908 A1 for instance, multilayer containers can also be used, whose barrier layers - for example made of ethylene vinyl alcohol copolymer (EVOH) or cycloolefinic components such as cycloolefin copolymers COC (trade name Topas) or cycloolefin polymers COP (trade name Zeonor)—minimize the permeation of the germicidal active substances of the fluid, especially oxygen or alcohols, into the interior of container i but not through the cap 4. It is also advantageous to use container headpieces having depressions in the head membrane, as shown in detail in DE 10 2013 012 809 A1.

[0027] An advantage of the procedure according to the invention is the very simple gravimetric or volumetric metering of the fluid via the liquid phase and the fact that the sterilization conditions can be easily adapted to the volume of the chamber 6, to the geometry of the container system and to its germ load via the quantity and concentration of the hydrogen peroxide solution (typically 3%-35%) introduced into the chamber 6, and can be controlled via the duration, the intensity and the pulse shape of the microwave. It has been found that a higher reduction in the number of germs can be achieved by several short-term microwave irradiation cycles than by a few, longer-lasting ones. Furthermore, it has been shown that increased hydrogen peroxide concentrations in the gas phase result advantageously in a reduction in the number of germs and the use of ethanolic-aqueous hydrogen peroxide solutions improves the wetting of the surfaces to be sterilized and thus also increases the germination reduction.

[0028] Experiments to prove the germ count reduction were performed by means of bio-indicators using spores of Geobacillus stearothermophilus. 0.02-0.2 ml of 35% aqueous H.sub.2O.sub.2 solution were metered onto the head membranes 8 of filled 250-ml-infusion bottles made of LDPE, the head membranes having different diameters (20-30 mm), and an HDPE cap 4 was welded on the head membranes 8. The volume of the chambers 6 formed in that way was in the range of approximately iml to approximately 3m1 on average. Sterilization experiments were performed using a microwave chamber having an adjustable microwave power of 0.6 KW to 6 KW and an MW transmission frequency of 2450 MHz. The direction of irradiation was parallel to the head membrane 8, i.e. perpendicular to the longitudinal axis of vessel 1. The filled area of vessel 1 was additionally shielded using a close-meshed wire net.

[0029] Surprisingly, a significant reduction in the germ count was achieved even in narrow gaps only a few millimeters wide, in particular between the head membrane 8 and the cap 4 and between the vessel head and the cylindrical part 10 of the cap 4. This was all the more successful the more frequently microcondensation occurred, i.e. for an increasing number of irradiation cycles and the resulting pressure pulses.

[0030] Moreover, the method in accordance with the invention permits a simple and direct verification of the leak-free application of the infusion cap 4, for instance verification by spectroscopic methods. For this purpose, the content of hydrogen peroxide in the gaseous phase and/or the oxygen content in the chamber 6 can be determined in a non-destructive manner. Laser absorption spectrometers having typical wavelengths in the infrared range between 760 nm and 2000 nm are suitable for this purpose. Alternatively, the concentration of gaseous hydrogen peroxide can be monitored and measured using photo fragmentation laser-induced fluorescence (PF-LIF).

[0031] Typically, low power levels are sufficient to generate the microwave pulses, preferably at frequencies of 896 MHz/915 MHz/922 MHz (L band) or 2450 MHz (S band) or 5.8 GHz (C band). When using radio waves (frequency range 5 MHz-50 MHz), more power is required due to the weaker coupling, but there is less interference, which significantly reduces so-called hot spots, which cannot always be avoided when using microwaves.