DE2164779C3 - Process for making sterilized articles - Google Patents

Description

The invention relates to the method for producing sterilized ones as defined in the claims Objects.

The inventive method is for the serial sterilization of objects, in particular of those for single use, used in the medical field and in hospitals in individual packaging suitable for storage and transport after the items were packed, excellently suited.

Most hospitals these days use in operating theaters and hospital rooms for sheets, Shawls, headgear, masks, towels and the like, common canvas. After using it will the dirty laundry is washed first, then sterilized in an autoclave and finally in one Cover made of canvas or paper packed to keep the laundry under sterile conditions until it is renewed is used. The sterile storage time for this combination is around 30 days.

Some hospitals today use packaged, pre-sterilized "disposable" linen. The packaged disposable laundry has a longer storage time than the linen made of linen, which is sterilized by the hospitals themselves. By using disposable linen, hospitals also have a cost saving because they no longer have to keep as many washing and sterilization systems and because they also save the work required to operate the systems that are no longer required. The term "laundry" is used here to refer to things such as B. bed sheets, hospital gowns, face masks, baby diapers and the like. Sterilized disposable items are also of interest to consumers; so can z. B. bandages, diapers, sanitary towels and tampons are sold in sterilized form.
The classic way to sterilize objects is to use superheated steam as the sterilant in an autoclave; this requires discontinuous work over a long period of time, and objects which are sensitive to heat and / or moisture are also adversely affected.

The need for full sterilization of some more heat and / or moisture sensitive Items that are used by doctors and hospitals has resulted in instead of Steam using ethylene oxide gas as a sterilant, which is not only extremely effective, but also the composition or the physical properties of heat and / or moisture sensitive Materials not changed.

The previously known such sterilization processes can be divided into 3 groups (cf. New packaging, 10/1960, pp. 926-932), namely the following:

a) The contents are sealed in gas-permeable plastic packaging with ethylene oxide sterilized.

The product is filled into largely gas-impermeable plastic packs, these are filled with ethylene oxide and then immediately sealed.
c) The contents are sterilized in the unsealed plastic packs by means of ethylene oxide and these are immediately closed after the gas has been removed.

So is known from US-PS 2938766 Sterilization process for disposable items - batch sterilization with ethylene oxide carried out in a large pressure vessel; it requires ■ 55 changes 7 steps and up to 7 hours after placing the disposable product to be sterilized in a gas impermeable Protective cover has been packed and placed in a pressure chamber. These stages are: (1) preheating, (2) applying a first vacuum, bo (3) introducing the sterilant into the chamber, (4) the product is exposed to the sterilant for up to 4 hours; (5) a second is applied Vacuum, (6) purging with sterile air, and (7) removing the packages. The sterilant must have the Penetrate packaging twice, first to get in and then to get out before the package can be removed from the pressure chamber.

b)

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The disadvantages of this previous method are that the objects to be sterilized can be packed on a conventional production line at high speed, However, that afterwards (1) the batch sterilization of the production flow prior to the storage of the packaged and sterilized items and causes a bottleneck in production, (2) the introduction of the sterilant in the package by means of penetration of the packaging by the gas from externally requires a relatively long period of time, and (3) sterilization by this method is proportionate is expensive.

Sterilization of the packaged goods with z. B. Ethylene oxide in an unsealed packaging ' Curing and closing of the latter before sterilization has taken place or after sterilization and removal of the sterilizing agent is similarly time-consuming and requires an interruption in the production line.

According to the discontinuous sterilization process known from US Pat. No. 3,476,506, the in an impermeable ampoule containing sterilization agent and the object to be sterilized together Enclosed in a gas-permeable outer package. After closing the Outer packaging, sterilization is initiated by breaking the ampoule, with the object exposed to the sterilant. The permeability of the outer packaging is a measure for controlling the concentration of the sterilant inside and outside the packaging. This sterilization method has the disadvantages that inside the packaging waste, namely the broken Ampoule, that it is a discontinuous process and that it is not easily attached to one Manufacturing process can be adapted.

The present invention is therefore based on the object of a packaging and sterilization method to provide that with high-speed conventional packaging production lines can be carried out without interruption. The solution to this problem is made possible by that the gaseous sterilant is introduced into the packaging very quickly, and that the gradual migration of the sterilant into the storage period of the end products will.

In accordance with the present invention, articles that are sterilized and pending use should remain sterile, individually packaged in gas-permeable packaging that is impermeable to bacteria. A load of gaseous sterilant then becomes rapid in any package introduced, and the packages are taken to a storage location where the sterilization process is completed by increasing the concentration of the sterilant inside the packaging decreases as it escapes through the packaging.

The invention is illustrated by the following detailed e> o Description explained in more detail with reference to the drawings.

Fig. 1 is a perspective view of one to be sterilized Item within the limits of its unsealed packaging, with 3 sides b5 are closed and the 4th side is still open;

Fig. 2 is a perspective view of the packaged After a vacuum is applied to the in-

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55 inside the packaging was put on and the 4th side was closed;

FIG. 3 is a section along line 3-3 of FIG Figure 2, which shows that there is no excess volume within the package after the vacuum is applied and the 4th side of the packaging is closed;

Figure 4 is a perspective view of the package after the sterilant has been introduced, the The injection needle used to introduce the sterilant has not yet been withdrawn.

The invention is explained on the basis of a preferred embodiment.

1 shows an object 11 which is partially closed in its own individual packaging 17 is. The packaging 17 can be formed by placing 2 sheets of the same size made of gas-permeable, Material impermeable to bacteria, namely the bottom sheet 15 and the cover sheet 16, placed one on top of the other and these two films are glued on three sides by means of closure strips 12, with an opening remains, which is so large that the object to be sterilized 11 between the two superimposed Packaging films can be introduced.

The packaging material is preferably a thermoplastic, heat-sealable material, that is gas-permeable and impermeable to bacteria. The permeability constants for each gas (usually expressed as: volume of gas allowed [at normal temperature and pressure], per Unit of time, per gas-permeable film surface, per gas partial pressure differential across the film, per Unit of film thickness, d. H. Volume / time / film area / pressure differential / film thickness) vary greatly depending on the nature of the sheet material, the changes being physical and chemical Properties of the film are related. Amorphous polymers have higher permeabilities than crystalline ones Polymers. For example, highly crystalline cellulose has a lower permeability than the less crystalline cellulose acetate. However, the crystallinity alone does not necessarily determine the transmission speed, as by an investigation of the permeability through polyethylene, polytrifluoromonochlorethylene and polyvinylidene chloride, all of which are crystalline polymers, but very much have different permeabilities. Polyvinylidene chloride is a symmetrical molecule with a high cohesive energy density and has a very low permeability. Polyethylene is even more symmetrical, but the cohesive energy density is much lower and it has a much larger permeability constant. Polytrifluormonochlorethylene is asymmetrical, but has a high cohesive energy density and has a permeability between the other two polymers. Therefore, the cohesive energy density is one Polymer is very important for its permeability.

In an unsymmetrical molecule, such as rubber hydrochloride, the poor symmetry, which adversely affects the molecular packing, leads to an open structure and consequently to a higher permeability. A similar effect should result from the branching of the polymer chains, as a branch leads to a less regular structure that cannot easily be arranged in a space lattice can. Hence there is an inverse correlation between the density and the permeability of a

Slide, d. that is, the lower the polymer density, the more its permeability increases.

An increase in the degree of crosslinking can be due to the stabilization of the segment movement that follows reduce the passage speed. It was found that irradiated polyethylene is less permeable than untreated polyethylene. On the other hand, increasing mobility increases the chains the easier passage.

The thermoplastic films are impermeable to bacteria as long as they are free of any holes are. Bacteria are much larger than gas molecules, therefore bacteria cannot get through a solid Foil can reach the smallest hole - even a gas pore - but can be enough for the bacteria to penetrate to enable. Therefore, the processing of a slide must be analyzed to determine whether There are gas pores in the film. So z. B. some foils processed electrostatically to the foil To give printability. However, these films are not useful as bacteria impermeable Foils, as this process can cause gas pores in the foil.

A 0.076 mm thick film made of low-density polyethylene commonly used in packaging technology has proven to be the preferred film for producing the packaging, as it has a moderately low permeability has and other requirements, such as. B. Availability, strength, low cost, Transparency, flexibility, aging hardening, fulfilled. Other heat sealable films that appear in more satisfactory Way that can be used are made of commercially available polypropylene and nylon. That used Polypropylene was biaxially oriented and 0.038 mm thick and is commercially available.

Heat sealable films are advantageous for use as packaging material because of conventional processes and equipment for heat welding can be applied to the connection between to effect the two superimposed foils of the packaging material. If because of his Permeability properties or any other properties a non-heat sealable Material is used as packaging material, the closure strip 12 can be between the two Sheets 15 and 16 of the packaging material are formed by adhesives that are bonded to the packaging material are compatible and which are known in adhesive technology.

The packaging 17, which acts as a sterilization chamber, must have suitable permeability properties have, d. H. it must contain the sterilant long enough to stay inside the package to effect sterilization, but it must use the sterilant also release so quickly that the concentration within the packaging during transport is so small that the risk of physical harm to people from further leakage is considerable is decreased. The sterilization of an object is dependent on an inverse function between the concentration of the sterilant and the time during which the object is exposed to it Concentration of the sterilant is exposed. The rate of permeability of a packaging material controls the concentration of the sterilant and the length of time during which this concentration is present. Therefore, choosing a packaging material with the appropriate one

Permeability properties are important when sterilizing inside a permeable package.

There are other methods of packaging article 11 in package 17, for example by the object 11 between two superimposed, heat-sealable sheets of the same Size, namely bottom film 15 and cover film 16 brings before one of the closure strips 12 is applied will; After this “stacking” of the base film 15 - object 11 - cover film 16, the closure strips 12 can be applied with any suitable device, e.g. B. with a heat pulse welding machine, as it is known in packaging technology and is commercially available.

The package 17 according to FIG. 1, which has been closed on three sides with a heat sealing device and into which the article 11 has been inserted, is ready to be completely closed.
It is advantageous to first expel all air from inside the package; therefore, a vacuum is applied to the interior of the package before the sterilant is introduced. The packages shown in Figures 2 and 3 show that a vacuum package removes all possible air.

The expelled air takes unwanted organisms with it and leaves more "free" space for the sterilant so that the sterilant can be introduced without an extremely high To exert internal pressure on the packaging. There is also no dilution of the sterilant on, and better diffusion and penetration by the sterilant occurs when the air has been removed from the packaging before the sterilant is introduced.

Preferably, the packaging of item 11 is completed by removing the fourth side of the package 17 welded in a commercially available vacuum welder. This is a machine which applies a vacuum to the package, clamps the open edge of the package and then the open edge The edge of the packaging is heat-sealed. The vacuum can also be applied to the packaging, after the package is completely closed, e.g. B. by piercing the packaging, to a Then vacuum and then welded again to create the vacuum inside the packaging maintain.

Various sterilants and concentrations of sterilants can be chosen.

Ethylene oxide is the most preferred sterilant because it is extremely effective and widely available and a mixture consisting essentially of nominally 12% ethylene oxide, 44% Freon 11 and 44% Freion 12, which is commercially available, is a preferred blend because of the limit of flammability this mixture is below that of ethylene oxide. Another sterilant that used is propylene oxide. These sterile agents are used at certain concentrations

Faotations toxic, flammable and explosive, and for these reasons, they must be handled carefully. For example, the maximum allowed is Concentration of ethylene oxide human exposure to 3000 ppm. Ethylene oxide has every

e, 5 is a natural warning factor, since it is at 700 pm irritates the nose and eyes, and in this way draws attention to the fact that one is potentially toxic condition exists. The recommended

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8 hour dose for ethylene oxide is 100 ppm; in comparison, a dose of 50 ppm is recommended for ammonia. It is flammable at concentrations greater than about 30,000 ppm in air, and when contained it is explosive. Liquid ethylene oxide boils, that vaporizes at about 10.6 ⁰ C at Ibar.

As shown in Figure 4, the sterilant through a hollow probe 13, e.g. B. a hyperchromic, stainless, subcutaneous injection needle No. 10 with a Luer approach, as it is known in injection technology and is commercially available, which is included in the packaging 17 is stabbed. The injection needle is attached to a standard gas syringe, which is also commercially available and which has a capacity of 1.5 liters. The syringe comes with the desired amount of the gaseous sterilant filled. The injection needle is pushed through a Foil of the packaging 17 pushed so that the delivery opening of the injection needle is within the The limits of the packaging 17 are located, and the sterilant is then passed through the injection needle 13 introduced into the packaging 17.

After the desired amount of the sterilant has been placed in the package 17, is the hypodermic needle 13 is removed from the package 17 and a sealing strip 14 is used, to close the opening remaining in the package after the needle 13 has been removed. the The opening is closed by covering it with the strip 14. Fig. 4 shows the packaging 17, which contains the sterilizing agent inside and on which the sealing strip ί4 is in one position is located, from which it can be used immediately to close the opening when the needle 13 is withdrawn will. The sealing strip 14 can be made of any material that is effective against bacteria Forms impermeable seal. Commercially available cellophane strips have proven to be sealing strips 14 well proven.

In an alternative embodiment of the method according to the invention, a high-pressure nozzle is used instead of the subcutaneous injection needle, which does not reach into the packaging 17, but allows the sterilizing agent to hit the outer surface of the packaging with such a high pressure that the narrow stream of the sterilizing agent through a wall the packaging 17 is forced. A device for introducing sterilant in this manner is similar to the pneumatic inoculation device used by the United States Armed Forces to vaccinate, forcing the serum through the epidermis of the "shot" recipient. A liquid sterilant is more easily introduced with the aid of this system than a gaseous sterilant, but the high-pressure nozzle introduces both a liquid and a gaseous sterilant. A sealing strip 14 is preferably also used in this case in order to close the opening produced in the packaging to 17 by admitting the sterilizing agent with a high pressure nozzle.

After the sterilant has been introduced into the package, it is placed in a storage room brought, in which the sterilization of the article 11 is completed. Any packaging 17 serves for the opposing

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50 stood 11 as a sterilization chamber and maintains the sterilant concentration for a sufficient time so that the object 11 and the interior of the package 17 are sterilized. The conditions in this storage room are not critical, with the exception that the storage room should be well ventilated. Ventilation is therefore necessary to prevent the concentration of the sterilant from increasing to values above the toxicity or flammability limit of the sterilant used. It is sufficient to completely change the air about once every minute in order to keep the sterilant concentration below 100 ppm, the maximum dose at which the package can be continuously exposed to the ethylene oxide when the ethylene oxide contains the e.g. B. 0.76 mm thick low density polyethylene film penetrates. If the storage space is not ventilated, increases in the concentration of sterilant are likely to occur as the sterilant is heavier than air and consequently will settle and fill a floor-to-ceiling space. The air removed from the storage space can be processed in order to remove the sterilizing agent contained in it or to render it harmless.

The temperature in the storage room can be varied to accommodate different sterilization times to obtain; In general, however, room temperature is sufficient to achieve satisfactory sterilization times. Temperatures of 21.1 ° C and above are preferred. At temperatures below 21.1 ° C the time required for sterilization can be very long. Higher temperatures lead to shorter sterilization times, because they accelerate the chemical process in which the bacteria are destroyed.

Having sufficient time for complete sterilization at a given sterilant concentration and a given temperature in the storage room, e.g. B. 6 hours at 22.8 ° C for 9.1% ethylene oxide, the packaging 17 can be removed from the storage room and taken to an ordinary storage room. When removing the sterilized packaging from the storage room, it must be taken into account whether the sterilization agent remaining in the packaging, after it has penetrated the packaging, accumulates in concentrations that the toxicity- or exceed the flammability limit. To be on the safe side, the packaging should 17 are preferably stored in the ventilated storage room until essentially that all sterilizing agent has penetrated the packaging; then too small an amount remains Sterilizing agent so that it could accumulate in concentrations above the hazard limit.

example 1

According to the US-PS Re. 26151 without plastic backing sheet manufactured, collapsed absorbent pad weighing 55.12 g and a size of 11.0 X 21.0 X 1.6 cm and a bacteria-germ strip were between two superimposed, above-mentioned 0.076 mm thick films of polyethylene lower Density previously determined along the three sides of the package to be made with a heat sealer had been heat-sealed.

The partially closed packaging was placed in the above-mentioned vacuum welding apparatus by applying a vacuum of about 980 mbar to the interior of the packaging and heat-sealing the fourth side of the packaging. The package was then removed from the vacuum sealer and sealed again with the heat sealer to ensure that the fourth side was securely closed. The dimensions of the package within the sealing strips were 12.7 X 23.0 X 1.0 cm, so that a packaging area of about 584.2 cm ^{2 was} obtained. 400 cm ^{3 of} the above nominally 12% ethylene oxide was filled into the above gas syringe from a pressurized container containing the sterilant at room temperature (21.1-23.9 ° C.) and atmospheric pressure. A No. 10 hypodermic needle was then placed on the gas syringe and stuck through a packaging wall into the disposable bandage. The gaseous mixture of sterilizing agents was then injected into the packaging, the needle was pulled out of the packaging, and a sealing strip of the above-mentioned cellophane tape was attached over the opening left by the needle. The package was then immediately moved to a constant temperature room of 22.8 ° C by storing it on an open, imperforate shelf with nothing placed on the package. The package was opened after 6 hours, and the seed strip was placed removed using sterile techniques, and in a tripticase soy broth culture solution and incubated for 7 days at 35 ⁰ C. The germ line culture shows that no living organisms remained in the package. It was sufficient to expose the packaging to the sterilant for 6 hours at 22.8 ° C to remove all bacteria in the packaging when the amount of sterilant was 400 ml of ethylene oxide, even if the sterilant was constantly escaping through the packaging.

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Example 2

A package was produced in which, as described in Example 1, an absorbent pad, a germ strip and a sterilizing agent were encapsulated; This package was placed in a room with a constant temperature of 49 ⁰ C and removed after two hours from the storage space with the temperature of 49 ° C.

ίο The germinal strip, as described in Example 1 removed and treated showed that no living organisms remained in the package. It was sufficient to expose the packaging to the sterilant for 2 hours at 49 ° C to remove all bacteria to be removed from the packaging if the amount of sterilization agent was 400 ml of ethylene oxide, even if the sterilizing agent was constantly escaping through the packaging.

Example 3

A packaging was made from the above-mentioned, 0.038 mm thick polypropylene film, encapsulated in the, as described in Example 1, an absorbent pad and a germ strip

and were injected with 500 ml of ethylene oxide. The packaging was then put in a room with a at a constant temperature of 49 ° C and after two hours out of the storage room with the Temperature of 49 ° C away. The germ line,

μ which was removed and treated as described in Example 1 showed that no living organisms remained in the packaging. It was sufficient to expose the packaging to the sterilant for two hours at 49 ° C to remove all bacteria in the packaging when the amount of sterilant was 500 ml of ethylene oxide, even if the sterilant was constantly escaping through the packaging.

It can therefore be seen that, according to the invention, a method for sterilizing the interior of the packaging has been provided which fully achieves the aforementioned objects and objectives.

1 sheet of drawings

Claims (3)

Patent claims: 1. A process for the manufacture of sterilized articles, wherein one a) one or more objects in gas-permeable, includes packaging impervious to bacteria, b) introduces a sterilizing agent into successive packages in such a way that the Sterilizing agent immediately comes into contact with the objects, with the amount of sterilizing agent introduced sufficient to cover the enclosed object and the interior surfaces and the interior space to sterilize the packaging, c) the packaging containing the sterilizing agent in a well-ventilated storage room brings and d) the packaging is stored in the storage room, with a substantial part of the sterilizing agent penetrating the packaging, so that the risk of physical harm to people during transport is significantly reduced through further penetration of the sterilizing agent, characterized in that the sterilizing agent is passed through a hollow probe injected, which is pierced into the packaging beforehand, and closes the opening that was created by pulling the probe out of the packaging after injection of the sterilizing agent. 2. The method according to claim 1, characterized in that the sterilizing agent through the packaging wall by passing a stream of the sterilant under high Pressure on the successive packagings and the opening that results has arisen that the sterilization medium flow in the packaging has penetrated under high pressure, seals. 3. The method according to claim 1 or 2, characterized in that one is used as the sterilizing agent Ethylene oxide used.