DE2164779A1 - Process for the manufacture of sterilized items - Google Patents

Description

«! ECHTSAMV / OLD

THERE. JIT. LM-OHEM-WALTER BEIT

rR JUR. CiPL-CHEM. H.-J. WOLFF DR. JÜÜ. HANS CHR. BtHL

FRANKFURTAMMAJN-HOCHSI, APAOHSTRASSi se

Our no.1.7 585

The Procter & Gamble Company Cincinnati, Ohio, V.St.A.

Process for the manufacture of sterilized items.

The invention relates to a method for the serial sterilization of objects in individual packages, which are suitable for storage and transport after the items have been packed. One or more items are sealed in a gas-permeable packaging, a sterilizing agent is introduced into the packaging, and the package containing both the item and the sterilant is attached to a well-ventilated one Relocation location moved where it will be held until sterilization is complete.

The invention relates generally to the serial sterilization of objects in individual packages according to the Manufacture, and in particular the sterilization of disposable items used in the medical field and in Used in hospitals.

209330/1096

Most hospitals these days use operating rooms and hospital rooms for sheets, handkerchiefs, headgear, masks, towels and the like. Usual- canvas.After use the dirty laundry is first washed, then sterilized in an autoclave and finally in a sleeve Canvas or paper wrapped to keep the laundry in sterile conditions until it is used again. the sterile storage time of this combination is about 30 days.

Some hospitals today use prepackaged, pre-sterilized "disposable" linen. The packaged disposable laundry has a longer storage time than linen made of canvas, which is sterilized by the hospitals themselves. Through the Using disposable linen, the hospitals also have a cost saving because they no longer have as much washing and washing Sterilization systems have to hold up, and because they are also the ones required to operate the systems that are no longer required Save work. The term "laundry" is used here to refer to things such as bedsheets, hospital gowns, face masks, baby diapers etc. include. Sterilized disposable items are also of interest to consumers, e.g. bandages, diapers, sanitary towels and tampons can be sterilized Form to be sold.

The classic way to sterilize items is to use superheated steam as the sterilant used in an autoclave, which implies that you work discontinuously in a large pressure vessel got to. However, items that require sterilization but are sensitive to heat and / or moisture are used adversely affected by the superheated steam. Also enables the discontinuous required for this process

2098-30 / 1090

It does not work smoothly along a production line, and superheated steam is not the most effective Sterilizer, that is, it does not turn off all living organisms, and you have to lengthen the items for Time to expose to superheated steam.

The need for full sterilization of some heat and / or moisture sensitive items that Used by doctors and hospitals has led to the search for more effective sterilants and was looking for faster procedures. Ethylene oxide gas has proven to be very effective and satisfactory as a sterilant proven to completely eliminate microorganisms and organic life. Ethylene oxide is not just extreme effective, but it also does not change the composition or the physical properties of heat and / or moisture sensitive materials.

Ethylene oxide is used in a sterilization process ₅ which is similar to the process in which superheated steam was used as the sterilization agent, since here too the sterilization is carried out intermittently in a large pressure vessel. The method of sterilization currently used by disposable article manufacturers is exemplary of that described in U.S. Patent 2,938,766. The process of this patent requires 7 stages, after which the disposable product is on its own. A gas-permeable protective cover has been enclosed and placed in a pressure chamber. These stages are: (1) preheating, (2) applying a first vacuum, (3) introducing the sterilant into the chamber, (4) the product:; ·;

209030/1098

the sterilant is turned off for up to 4 hours sets, (5) applying a second vacuum, (6) flushing with sterile air and (7) removing the packages. The procedure takes up to 7 hours to complete the 7 levels. The sterilant must be wrapped twice penetrate, first to get in and then to get out, before the package leaves the pressure chamber can be removed.

The disadvantages of previous methods are that (1) the batch mode allows the smooth flow of a Interrupts the production line and causes a bottleneck, (2) the introduction of the sterilant into the Package requires a longer period of time on the product due to the gas penetrating the packaging, and (3) sterilization by this method is relatively expensive.

Another method for sterilizing objects in a package is described in US Pat. No. 3,476,506, the one sterilization apparatus for discontinuous sterilization in relatively rare cases (on a relatively infrequent basis). That sterilization? agent, which is contained in an impermeable ampoule, and the object to be sterilized are together in one gas-permeable outer packaging included. After the outer packaging has been closed, the sterilization initiated by breaking the ampoule exposing the item to the sterilant. The permeability the outer packaging is a measure of the control of the concentration of the sterilant inside and

209530/1098

outside of the packaging. This sterilization process has the disadvantages that waste, namely, the broken ampoule, what remains is that it is a discontinuous process and that it is not easy can be adapted to a manufacturing process.

The present invention is therefore based on the object of producing sterilized objects that can be used in individual, Packagings impermeable to bacteria are sterilized in such a way that they remain in the packagings for a longer period of time Period of time can be handled and stored and still remain sterile, with the packaging and sterilization process can be matched with fast-running packaging tapes and the gaseous Sterilizing agent is introduced very quickly into the packaging and then the permeability of the packaging represents a measure for controlling the concentration of the sterilizing agent and the gradual migration of the sterilizing agent.

In accordance with the present invention, articles that are sterilized and remain sterile until used should, individually packed in gas-permeable packaging that is impermeable to bacteria. A batch of one Gaseous sterilant is introduced into each package and the packages are sent to a storage location where the sterilization process is completed and the concentration of the sterilant inside of the packaging is reduced as the sterilizing agent penetrates the packaging.

209830/1090

The invention is explained in more detail by the following detailed description 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 sealed and the 4th side is still open.

Fig. 2 is a perspective view of the packaged article; after a vacuum was applied to the inside of the packaging and the 4th side was closed.

FIG. 3 shows a section along the line 3-3 of FIG. 2 which shows that there is no excess volume inside 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 insertion of the sterilant, with the injection needle used to introduce the sterilant still is not pulled out.

The invention is based on a preferred embodiment explained.

Fig. 1 shows an object 11, which in its own, individual Package 17 is partially closed. The packaging 17 can be formed by placing 2 films of the same size made of gas-permeable, bacteria-impermeable material,. namely the bottom film 15 and the cover film 16, one above the other lays and these two foils are glued on three sides by means of closure strips 12, an opening remaining so

209830/1098

it is great that the object to be sterilized 11 is inserted between the two packaging films lying one above the other can be.

The packaging material is preferably a thermoplastic, hitζ weldable material that is gas-permeable and is impermeable to bacteria. The permeability constants for each gas (usually expressed as: volume of the gas allowed through [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, i.e. 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, such as shown by a study of the permeability through polyethylene, polytrifluoromonochlorethylene and polyvinylidene chloride which are all crystalline polymers but have very different permeabilities. Polyvinylidene chloride is a symmetrical molecule with a high cohesive energy densityjund 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. Polytrifluoromonochlorethylene is asymmetrical, but has a high cohesive energy density and has a permeability between the other two polymers. thats why the cohesive energy density of a polymer is very important for its permeability.

209830/1098

In an unsymmetrical molecule, like rubber hydrochloride, ' leads to the poor symmetry that affects molecular packing to a more open structure and consequently to a higher permeability. A similar effect should turn out the branching of the polymer chains, as branching leads to a less regular structure that is not easy can be arranged in a space grid. Hence there is an inverse correlation between density and per- ' permeability of a film, i.e. the lower the polymer density, the more its permeability increases.

An increase in the degree of networking can be due to the resulting reduce the passage speed following stabilization of the segment movement. So 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. bacteria are much larger than gas molecules, so bacteria b cannot get through a solid film, the smallest hole - even a gas pore - can, however, be sufficient to allow the bacteria to penetrate. Therefore, the processing of a Foil can be analyzed to determine if there are gas pores in the foil. For example, some foils become electrostatic processed to give the film printability. However, these films are not useful as against Bacteria impermeable films, as this process can cause gas pores in the film.

209830/1098

A 0.076 mm thick sheet of low density polyethylene, known in the packaging art and commercially available from Ethyl Corporation, Baton Rouge, La. as hi-slip shrink Visqueen Film has been found to be the preferred film for making the packages because of its moderately low permeability and other requirements such as e.g. availability, strength, low cost, transparency, flexibility, aging hardening, fulfilled. Other heat breakable Films that can satisfactorily be used are polypropylene and nylon. That used Polypropylene was biaxially oriented and 0.038 mm thick and was commercially available from Hercules, Inc., Wilmington, Del. as BC 120 available.

Heat sealable films are advantageous for use as packaging material since conventional methods and systems for heat sealing can be used to create the bond
between the two lies on top of one another, to effect λ de η foils of the packaging material. If a non-heat-sealable material is used as the packaging material because of its permeability properties or any other properties, the closure strip 12 can be formed between the two sheets 15 and 16 of the packaging material by adhesives which are compatible with the packaging material and which are known in the adhesive art.

The packaging 17, which acts as a sterilization chamber, must have the appropriate permeability properties, i.e. must contain the sterilant long enough to inside the package to effect sterilization, but it must also release the sterilant so quickly that

209830/1098

the concentration within the packaging during transport is so low that there is a risk of physical harm to people is considerably reduced by further leakage. The sterilization of an object depends on a reverse puncture between the concentration of the sterilant and the time during which the item is held is exposed to this concentration of the sterilant. The rate of permeability of a packaging material controls the concentration of the sterilant and the length of time that concentration is maintained · Therefore, selecting a packaging material with the appropriate permeability properties is important when is sterilized within a permeable package.

There are other methods of packaging the item 11 in the package 17, for example by placing the item 11 between two superimposed, heat-weldable foils of the same size, namely bottom foil 15 and cover foil 16 brings before one of the closure strips 12 is applied; after this "stacking up" of bottom sheet 15 - item 11, cover sheet 16, the fastener strips 12 can be applied by any suitable means, such as a heat impulse heat sealer, as known in packaging technology and commercially available from Vertod Company, Brooklyn, N.Y. (hereinafter referred to as a heat sealer) is available.

The package 17 according to Pig. 1, which was sealed on three sides with a heat sealer and into which the object 11 is ready to be closed completely. If the packaging as a sterilization chamber

209830/1098

is used, it is advantageous to first expel all air from the inside of the package, so a Vacuum is applied to the inside of the package before the sterilant is introduced. The in Figures 2 The packages shown in Figures 3 and 3 show that a vacuum package removes any 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 exerting an extremely high internal pressure on the packaging. It also occurs no dilution of the sterilant occurs, and better diffusion and penetration by the sterilant occurs as the air is removed from the package has been 'before the sterilant is introduced.

Preferably, the packaging of article 11 is completed by the fourth side of the package 17 in one Vacuum sealer welded. This is a machine that applies a vacuum to the package, the open edge the packaging and then heat-sealing the open edge of the packaging. A type of vacuum sealer it is that of Standard Packing Corporation, New York, N.Y. marketed vacuum sealer with the designation Flex Vac. The vacuum can also be applied to the packaging after the packaging is completely closed is, for example, by piercing the packaging, connecting it to a vacuum and then re-sealing it, to maintain the vacuum inside the packaging.

Various sterilizing agents and concentrations of sterilizing agents can be chosen. Ethylene oxide is the most preferred sterilant as it is extremely

209830/1098

is effective and commonly available, and a mixture consisting essentially of nominally 12 % ethylene oxide, hH% Freon 11, and 44 % Preon 12, commercially available from The Matheson Company, Inc., East Rutherford, NJ, provides one The preferred mixture because the flammability limit of this mixture is lower than that of ethylene oxide. Another sterilant that could be used is propylene oxide. These sterilants are both noxious and dangerous, that is, they become toxic, flammable and explosive at certain concentrations, and for these reasons they must be handled with care. For example, the maximum allowable concentration of ethylene oxide that humans can be exposed to is 3,000 parts per million (ppm), but ethylene oxide has a built-in warning factor because at 700 ppm it is irritating to the nose and eyes and thus draws attention steers the fact that a potentially toxic condition exists. The recommended 8 hour dose for Ethyleno:; id is 100 ppm; in comparison, a dose of 50 ppm is recommended for ammonia. In concentrations greater than about 30,000 ppm in air is flammable ent _t '■ and if it is included, it is explosive. Liquid ethylene oxide boils, ie evaporates, at about 10.6 ° C at 1 atm pressure.

As shown in Fig. 4, the sterilant can be passed through a hollow probe 13 such as a hyperchromic, stainless, subcutaneous Injection needle no. 10 with a Luer hub, like her known in injection technology and from Beeton, Dickinson & Co., Rutherford, N.J., which is pricked into package 17. The hypodermic needle is attached to a standard gas syringe that is in the

209830/1098

Known in the art and commercially available from Hamilton Co., Inc. Whittier, California as Super Syringe, Model No. 3-15G0 and which has a capacity of 1.5 liters. The syringe is filled with the desired amount of the gaseous sterilant. The hypodermic needle is pushed through a foil of the packaging 17 so that the dispensing opening of the hypodermic needle is within the confines of the "packaging 17", and the sterilant is then introduced through the hypodermic needle 13 into the packaging 17. After the desired amount of sterilization agent was placed in the packaging 17, the injection needle 13 is removed from the packaging 17, and a sealing strip Ik is used to close the opening remaining in the packaging after removing the needle 13. The opening is closed by closing it with the strip Fig. 4 shows the packaging 17 which contains the sterilizing agent in its interior and on which the sealing strip 14 is in a position from which it can be used immediately to close the opening when the needle 13 is pulled out 14 can be made of any material that is impervious to bacteria Conventional cellulose strips, such as the strip sold under the Scotch trademark by the Minnesota, Mining, & Manufacturing Company of St. Paul, Minnesota, have performed well as the sealing strip 14.

There are other methods of maintaining a sterilizing atmosphere within a sealed package. One An alternative to the subcutaneous injection needle is a ΗοΛ-hrlruck'lüsr-- ·, which does not reach into the packaging 17,

BATH ORIGINAL

but allows the sterilizing agent to hit the outer surface of the packaging with such a high pressure that the narrow stream of sterilizing agent is forced through a wall of the packaging 17. 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 sterilization medium W is easily inserted using this machine as a gaseous sterilant, however, the high-pressure nozzle results in both a liquid and a gaseous sterilization agent. A sealing strip 14 is preferably also used in this case in order to close the opening produced in the packaging 17 by admitting the sterilizing agent with a high pressure nozzle.

A third method to get in a sterilizing atmosphere Bringing a package 17 consists in placing the package within an atmosphere of sterilization with.-o?, £. £ forms, fills and seals. The sealed package 17 with enclosed sterilizing agent is then removed the sterilizing atmosphere is moved to the storage location. This method is particularly suitable for use with one of the non-explosive sterilizing gas mixtures.

After the sterilant has been introduced into the package, it is placed in a storage room, in which the sterilization of the item 11 is completed, each package 17 is used for through it included item 11 as a sterilization chamber and

Ö 8

maintains the concentration of sterilant long enough so that the article 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 to keep the sterilant concentration below 100 ppm, the maximum level at which the package can be continuously exposed to ethylene oxide when the ethylene oxide penetrates the 0.076 mm thick, low-density polyethylene film . If storage space is not ventilated, probably increases take place the sterilizing agent concentration, since ^one sterilant is heavier than air and settle hence and will fill a room from the ground sur ceiling. 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 get different sterilization times; in the generally sufficient, but room temperature to achieve more 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.

209830/1098

After a sufficient time for complete sterilization at a given sterilant concentration and a given temperature in the storage space, for example, is passed at 22.8 ⁰ C for 9.1% of ethylene oxide 6 hours the package 17 from the storage space can be removed and ordinary in a Storage room to be brought. When removing the sterilized packaging from the storage room, it must be taken into account whether the sterilizing agent remaining in the packaging, after it has penetrated the packaging, accumulates in concentrations that exceed the toxicity or flammability limit.To be completely safe, the packaging should 17 are preferably stored in the ventilated storage space until essentially all of the sterilizing agent has penetrated the packaging; then too small an amount of sterilizing agent remains for it to accumulate in concentrations above the risk limit.

example 1

One of AEEN teachings of US Patent No. Re. 26 151, made without a plastic support film, folded absorbent pad with a weight of 55.12 g and a size of 11.0 21.0 χ 1.6 cm and a bacterial spore strip, e.g. Spordex (Manufacturer: American Sterilizer Company of Erie, Pennsylvania) were placed between the two superimposed, aforementioned 0.076 mm thick films of low density polyethylene which had previously been heat sealed along the three sides of the package to be produced with a heat sealer. The partially closed

209830/1096

Package was placed in the aforementioned vacuum sealer (Flex Vac) in which a vacuum of about 737 mm Hg was applied to the interior of the package and the fourth side of the package was heat sealed. The package was then removed from the vacuum sealer and sealed again with the heat sealer to ensure that the fourth side was tightly closed. The dimensions of the packaging within the sealing strips were 12.7 × 23 ₉ O I ₃ O cm, so that a packaging area of about 584.2 cm was obtained. iJOO cnr of the above-mentioned nominally 12 #igen ethylene oxide-containing container at room temperature (2I ₉ I 23a9 ° C) and atmospheric pressure were placed in the above-mentioned gas from a pressurized syringe, the sterilizing agent. Then an injection needle No. ₀ 10 was placed on the gas syringe and through a packaging wall into the . single use certain sanitary napkins. Then, the gaseous sterilizing agent mixture was injected into the package, withdrawing the needle from the package and a sealing strip of the above Gellophanbandes mounted üfoei * the left by the needle aperture "The package was flann immediately into a room with a ⁵ constant temperature vr-Γί 22 brought 8 ^c * c in which it was in an open ftelagert _s imperforate shelf ₀ vobet nothing WUfOe placed on the packing _9, the packaging opened after β mirde hours and the Ksirastreifen wame imter using sterile techniques away- un €. lived in a Tpiptiease soy broth-Kultin ⁰ solution and 7 x £ ge long established 3 ^ 0 tiebrüteto The Keiai ° grazing s culture rappelled "because & k © £ O6 lebsäiöso Organisraeii remained in Vei'packung .: It geriögfcer, dis Packaging dem lization agent 6 Stm ^- ; s9E Xanß at 32 _Ρ 8 ^ο 0 aussixsefcssn _s . camouflage

remove all bacteria in the package if the crowd of sterilizing agent was 400 ml of ethylene oxide, too if the sterilant was constantly escaping through the packaging.

Example 2

A package was made in which, as described in Example 1, an absorbent pad, a germ strip and a sterilant were encapsulated; this package was placed in a room with a constant temperature of 49 ° C and removed from the storage room with the temperature of 49 ° C after two hours. The germ strip, which was removed and treated as described in Example i, showed that no living organisms remained in the packaging. It was sufficient to expose the packaging to the sterilant for 2 hours at H9 ° C to remove all bacteria in the packaging if the amount of sterilant was 400 ml of ethylene oxide, even if the sterilant was constantly escaping through the packaging.

Example 3

Mentioned above from which OjO38 mm thick polypropylene sheet was a packaging _s prepared as described in Example 1 in Figure _4, an absorbent pad and a seed strips were encapsulated were UNAE injected into the 500 ml of ethylene oxide, "The package was then constant in a space with a Temperature of 4 ^ 'C and removed after two hours from the storage room with the temperature of 49 ° C. The germ strip, eggs as in example i

was described, removed and treated showed that none living organisms remained in the packaging. It was enough to wrap the sterilant for two hours at 49 "C to expose to all of the bacteria in the package to remove when the amount of sterilant was 500 ml of ethylene oxide, even if the sterilant was constant escaped by penetrating the packaging.

It can thus be seen that the invention provides a method for sterilizing the interior of the packaging which fully meets the above objectives and tasks.

209830/1098

Claims (11)

Patent claims: 1. A method for producing sterilized objects, characterized in that one a) encloses one or more objects in gas-permeable packaging impermeable to bacteria, b) introduces a sterilizing agent into successive packages in such a way that the sterilizing agent is immediately comes into contact with the objects, wherein the amount of sterilizing agent introduced is sufficient to the enclosed To sterilize the object and the inner surfaces and the interior of the packaging, c) brings the packaging containing the sterilizing agent into a well-ventilated storage room and d) the packaging is stored in the storage room, a substantial part of the sterilizing agent being the Packaging penetrates, so that there is a risk of physical harm to people during transport through further penetration of the sterilant is substantially reduced. 2. The method according to claim 1, characterized in that ψ preparing the packaging of a thermoplastic, heat-sealable film. 3. The method according to claim 2, characterized in that a 0.076 mm thick polyethylene film is used as the film . 4. The method according to any one of claims 1 to 3, characterized in that that ethylene oxide is used as a sterilant. 209830/1098 5. The method according to any one of claims 1 to 4, characterized in that that the sterilant is injected through a hollow probe that has previously been pierced into the packaging will. 6. The method according to claim 5, characterized in that the opening made by pulling the probe out of the Packaging created after injection of the sterilizing agent is closed. 7. The method according to any one of claims 1 to 4, characterized characterized in that the sterilant is introduced through the packaging wall by passing a stream of the sterilant can hit the successive packagings under high pressure. 8. The method according to claim 7 » characterized in that the opening, which has arisen in that the stream of sterilizing agent has penetrated into the packaging under high pressure, closes. 9. A method according to any one of claims i to 8, characterized in that the object or objects under vacuum in the separate one gas permeable _s closes for bacteria impermeable packaging. » 10. The method of claim I ₅ characterized in that the inclusion of the one or §egenstände in gas-permeable, bacteria-impermeable packages in a Sterilieationsraittel atmosphere öEwehfühPtj wherein the sufficient amount of the sterilizing sur SterilisatiosisEiittels enclosed in consecutive packages. 11. A sterilized article that has been packaged and treated by the method of claim 1. For: The Procter & Gamble Company Cincinnati, Oh / ίο, V.St.A. (Dr H.J. Wolff) Lawyer