MX2008001780A - Membrane sterilization - Google Patents

Abstract

A method for disinfecting or sterilizing an article comprising enclosing the article or article part inside a container having a wall of which at least a part is a semipermeable fabric or membrane and introducing an amount of vaporizable biocide, preferably hydrogen peroxide in water, to the interior of said container in solution, vapour, liquid or preferably nebulant form. The semipermeable fabric or membrane is selected to allow the biocide to pass from inside to outside of the container as a vapour at atmospheric pressure and to provide a barrier against entry of micro-organisms. The biocide is allowed to exit the container through said membrane while at or above atmospheric pressure, a fluid eg air is directed to flow adjacent the outside of the membrane to expedite vapour removal from the interior side. The article is exposed to the biocide for a time sufficient to disinfect or sterilize the article.

Description

STERILIZATION WITH MEMBRANE FIELD OF THE INVENTION This invention relates to a method for disinfecting or sterilizing a surface and is a modification or improvement of the invention described in our co-pending application entitled "Enhanced Aerosol", the content of which is incorporated herein by reference. The method has a particular application for disinfecting or sterilizing medical instruments, but is not limited to that use. Although the invention is capable of sterilization, it will be understood that the invention can also be advantageously used for high level disinfection and disinfection. References in the present sterilization include disinfection, where the context admits it.

BACKGROUND OF THE INVENTION In our copending application there is disclosed a method for disinfecting or sterilizing a surface comprising the steps of: (1) nebulizing a solution comprising a sterilizing agent in a solvent, to form a mist of finely divided particles of the solution in a gas stream , the solution includes a solvent that has a lower boiling point than the sterilizing agent; (2) subjecting the nebulizer to energy of a kind and for a duration sufficient to vaporize the solvent, preferably to the sterilizing agent, whereby the concentration of the agent in the nebulized particles is increased; (3) remove the vaporized solvent in step 2 from the gaseous stream at or above atmospheric pressure and, if necessary, cool the mist to below 70 ° C; and (4) exposing the surface to the nebulizer of step 3 for a sufficient time to sterilize the surface. The main advantages of that process is that (a) the need for vacuum associated with the commercial steam processes of the prior art is avoided, (b) the need for a rinsing step associated with the commercial solution processes of the prior art, and (c) the need for temperatures above 60 ° C, which are harmful to many materials, and (d) is more effective than nebulization and steam processes of the prior art, especially when treated occluded surfaces, which coincide and with a lumen. In the preferred embodiments, it uses hydrogen peroxide at concentrations which are not classified as skin irritants and which are safe to transport and handle (unlike commercial steam and plasma procedures, which use peroxide solutions at 60% corrosive and irritants, which require special packaging and handling precautions). The prior art is widely discussed in our co-pending application. We have now discovered that at least some of the benefits produced by the method of our co-pending application can be achieved simply by alternative means with some surprising additional and unexpected advantages. Any discussion of the prior art through the specification should in no way be construed as an admission that such prior art is widely known or forms part of the general knowledge common in the field. The present invention arose from the need for a method for sterilizing diagnostic ultrasound ("DU") probes. These instruments are used for a variety of intracavity procedures, including intrarectal, intravaginal and esophageal examination, and should be sterilized to avoid cross infection. The instruments are sensitive to temperature and can not be heated above 55-60 ° C. Several different plastics can be used in their external construction, which may involve joined or matching parts. DU probes have electrical connectors that are sensitive to corrosion. Frequently, the procedures are of short duration, but sterilization can take much longer than a procedure, therefore, a multiplicity of instruments is needed to allow the procedures to be carried out during the long sterilization cycles. Each instrument is expensive and the need for multiple instruments adds greatly to the cost of exams. further, procedures are often performed in locations where there is no access to centralized or specialized sterilization equipment, such as plasma sterilizers, which employ high vacuum and cost more than $ 100,000. Currently, DU probes are commonly disinfected using high-level disinfectants, such as glutaraldehyde or liquid OPA (ortho phthalyl aldehyde), both of which are associated with a high risk to Occupational Health and Safety, as well as a risk to the patients for the waste. Currently, no sterilization procedure is available for these instruments, and high-level disinfection is not considered fully satisfactory by the health professionals who use these instruments. It will be understood that the invention is not limited to the use for sterilizing DU probes and can also be used to disinfect or sterilize other articles or surfaces. In addition, DU probes are not usually stored in a sterile environment, and best practice requires that, in such cases, they are disinfected immediately before use. Cummins 4744951, describes a process in which hydrogen peroxide is vaporized and concentrated in a first chamber by means of heat and pressure reduction (for example, 0.01 atmospheres). Water vapor is preferably extracted from the vapor of hydrogen peroxide through a vacuum pump. The peroxide vapor thus concentrated is then admitted into an evacuated sterilization chamber, in which it is allowed to come into contact with an article to be sterilized. The process suffers from the main disadvantages that are associated with the need for a vacuum and evacuation system.

OBJECTS OF THE INVENTION It is an object of the invention to provide improved means for disinfecting or sterilizing medical instruments, which avoids or lessens at least some of the disadvantages of the prior art. It is an object of the preferred embodiments of the invention to provide improved disinfection or sterilization means, suitable for the treatment of ultrasound probes, or ultrasound radiology probes, without requiring the reduction of pressure. Unless the context clearly requires otherwise, through the description and claims, the words "comprises", "comprising" and the like must be considered in an inclusive sense as opposed to an exclusive or exhaustive sense; that is, in the sense of "including, in a non-exclusive manner".

BRIEF DESCRIPTION OF THE INVENTION According to a first aspect, the present invention provides a method for disinfecting or sterilizing an article or part of an article, comprising the steps of (1) enclosing the article or part of the article within a container having a wall in the container. which at least one part is a semi-permeable fabric or membrane; (2) introducing a quantity of vaporizable biocide into the interior of the container; (3) the semipermeable fabric or membrane is selected to allow the biocide to pass from the interior to the exterior of the container as a vapor at atmospheric pressure and to provide a barrier against the entry of microorganisms; (4) allow the biocide to exit the container through the membrane, while at or above atmospheric pressure; and (5) exposing the article or part of the article to the biocide for a sufficient time to disinfect or sterilize the article. By preference, the entire process is performed at atmospheric pressure and sufficient of the biocide is removed, so that the residue of the biocide, if any, in the article or part of the article is at or below acceptable levels. According to a second highly preferred aspect, the present invention provides a method for disinfecting or sterilizing an article or part of the article, comprising the steps of: (1) enclosing the article or part of the article within a container having a wall in which at least one part is a semi-permeable fabric or membrane; (2) introducing a biocide as a nebulizer into the container; (3) the semipermeable fabric or membrane is selected to allow vapor to pass from the interior to the exterior of the container, while providing a barrier against the entry of microorganisms and against the exit of the nebulized particles; (4) allow steam to exit the vessel through the membrane or above atmospheric pressure; and (5) exposing the article or part of the article to the nebulizer for a sufficient time to disinfect or sterilize the article. According to a third aspect, the invention provides a method according to the first or second aspect, wherein a fluid is directed to flow adjacent to the outside of the membrane, for rapid removal of the vapor from the inside. By preference, the fluid is air, more preferably, air conditioning with moisture. According to a fourth aspect, the invention provides a method according to any of the preceding aspects, wherein the biocide is a solution of hydrogen peroxide in water. The semipermeable fabric or membrane selected according to the third step of the method, can be a woven or non-woven fabric, or it can be a sheet or a film or a combination thereof, and can be of a single-layer construction or with multiple layers. The term "semipermeable membrane" is used herein, wherein the context allows to include all such fabrics and membranes having the selected properties. The semipermeable membrane can be hydrophobic or hydrophobic in nature. In the first step of the method, the article to be sterilized is enclosed in a container having a wall, of which at least a part is a semipermeable membrane. In some cases, the entire article does not need to be sterilized, and it is sufficient to enclose the part of the article that requires treatment. By "enclose", it is meant that the article or at least the part to be disinfected, is enclosed in the container, in such a way that after sterilization (which takes place inside the container), no microorganism can enter the container or get in touch with the locked portion of the article, while remaining locked. It will be understood that although the invention is capable of being used for sterilization (ie achieving a reduction of log 6 is the spores), it can be used with advantage to achieve a lower standard of disinfection. The container may be a rigid or semi-rigid chamber constructed of, or having openings covered by, the semi-permeable membrane or may be a chamber, pouch or pocket formed in the semi-permeable membrane. In the second step, a biocide is introduced into the interior of the container. In preferred embodiments, the biocide is a hydrogen peroxide solution that is nebulized, and the nebulizer is then introduced into the interior of the container. In a highly preferred embodiment, a peroxide solution having an initial concentration of at least 6%, preferably 20% -35%, and more preferably 30% -35%, is nebulized. Preferably, the solution is nebulized in an ultrasonic nebulizer operated at 2.4 MHz, which generates an aerosol in which the particles having a distribution in the size range of about 1-10 microns are suspended in a stream of air. As used herein, the term "nebulized" describes droplets of liquid (ie, particles of finely divided liquid) entrained in a gas stream. A system of droplets of liquid entrained or suspended in a gas is an "aerosol". In the preferred embodiments, the container is provided with sealable means for introducing a fluid, whereby aerosol nebulization can be admitted into the interior of the container. The sealable means may, for example, be an inlet opening, provided with a shut-off valve, or with a one-way valve, which allows fluid to enter the container, but which prevents fluid outflow, or a tube that communicates with the interior, and capable of being sealed with heat, or it can be a self-sealing septum capable of being pierced by a nebulized injection nozzle. By any such means, an aerosol outlet of the nebulizer is placed in communication with the interior of the enclosure via the inlet opening. However, it will be understood that in other embodiments, the aerosol can be introduced by being generated within the interior of the container or within a compartment in communication with the container, so that the container can be sealed before the aerosol is formed. The third step of the method, in combination with the fourth, allows the vapor to permeate out of the chamber through the semipermeable membrane at atmospheric pressure. The semipermeable membrane is selected with respect to the need to provide a barrier for the entry of microorganisms and that requirement ensures that the nebulized particles are initially unable to permeate out and concentrate (particles per liter) in the container. Without wishing to adhere to a theory, it is believed that as the water vapor permeates out of the container through the membrane as described hereinafter, and as the air permeates in, the water evaporates from the drops of the nebulizer with the In order to restore the equilibrium vapor pressure inside the container. The continuous evaporation of the droplets results in the peroxide solution in the nebulizer becoming more concentrated, and in that the droplets shrink in size. As our co-pending application shows, these smaller concentrated nebulized particles, are significantly more effective as a sterilant than the hydrogen peroxide vapor of the prior art, and the sterilizers and processes with peroxide nebulization of the prior art. The air that permeates into the container is sterile because the membrane is not penetrable by the microorganisms. The article or part of the article is exposed to the nebulizer for a sufficient time to disinfect the article at a desired level or to sterilize it. The container can be sealed after sufficient nebulization has been introduced into the container. This may take place before or after the article has been completely disinfected or sterilized, and before or after substantially all of the water vapor has been removed. In the case where the inlet is provided with a one-way valve, the container is sealed in the relevant sense at all times, after the article or part of the article has been enclosed. Eventually, the nebulized particles vaporize completely and pass through the semipermeable membrane, leaving the dry and free content of the harmful residue. In the highly preferred embodiments of the invention, a fluid is allowed to flow adjacent to the outside of the membrane for rapid vapor removal from the interior. Preferably, the fluid is air, more preferably, it is preconditioned air (eg, dehumidified air). The air flow provides an "external current" that eliminates the molecules that permeate to the outside of the membrane, which improves the efficiency of the elimination of the vapor inside the container. The term "outside stream" is used herein to denote an air flow on the side of the outer membrane of the interior of the container, and while the direction of flow will usually be in the opposite direction to that of the nebulized to the container , that is, a "countercurrent", the direction of the flow is not critical, and where the context admits the term "external current", it does not pretend to imply any particular flow direction, and it includes a countercurrent.

According to a fifth aspect, the invention provides a method according to any of the preceding aspects, wherein the semipermeable membrane is selected to remove one or more vapors by a pervaporation process. Although the invention is described herein with reference to hydrogen peroxide as the biocide, it is considered that the invention will be equally applicable when the biocide is other than peroxide or a peroxy compound, or it can be used with other known vaporizable biocides or biocides when the suitable solvents (which do not need to be aqueous) are dissolved. In addition, although it is highly preferred to introduce the biocide as an aerosol, in the less preferred embodiments, the biocide can be introduced as a vapor, and the vapor is subsequently removed at atmospheric pressure by an outside air stream (or other fluid), adjacent to the outside of the membrane. The introduction of the biocide as an aerosol is largely preferred because much higher initial densities of the biocide can be achieved per liter of the container than with a vapor. Our co-pending application indicates that the aerosols according to the invention, which are believed to be the same or similar to the aerosols produced in this process, are more effective than the vapor. In other aspects, the invention provides apparatus for performing the method, containers for use in the method, and compositions formed during the use of the method.

According to a sixth aspect, the present invention provides a method for disinfecting or sterilizing an article or part of the article, comprising the steps of (1) enclosing the article or part of the article within a first container having a wall , of which at least one part is a semi-permeable fabric or membrane; (2) the semipermeable fabric or membrane is selected to allow the vapor to pass from the interior to the exterior of the container, while providing a barrier against the entry of microorganisms and against the exit of the nebulized particles; (3) admitting a biocide solution comprising a biocide dissolved in a solvent to the second container; (4) concentrating the biocide in the second container by removing the solvent at atmospheric pressure, to form a concentrated bichocide (5) introducing the concentrated biocide as a liquid or a vapor or a combination thereof, from the second container to the first; and Y wherein the steps (3) - (5) are performed at or at approximately atmospheric pressure. In the preferred embodiments according to the sixth aspect, the invention is performed in a manner similar to that described by Cummins, but differs in that a solution of hydrogen peroxide in water, of for example, a concentration of 35%, is concentrated first as a nebulized in a chamber by removing water through a membrane at atmospheric pressure. The concentrated nebulizer is then admitted into another chamber, which is in a desired manner a bag or other container having a semipermeable membrane, defined as a wall or part thereof which is then sealed. This allows the article to be sterilized and stored sterile in the second container and allows the removal of the residual hydrogen peroxide. In the alternate embodiments of the fifth aspect, the concentrated hydrogen peroxide is admitted to the first container as a concentrated vapor.

BRIEF DESCRIPTION OF THE DRAWINGS The invention will be described more particularly by way of example only, with reference to the accompanying drawings, wherein: Figure 1 is a schematic diagram in vertical cross section (not to scale) of a first embodiment of a container for use in the invention . Figure 2 is a schematic diagram showing a flow diagram of one embodiment of a method of the invention, which employs a container according to the first embodiment.

Figure 3 is a schematic diagram showing a flow chart of a more sophisticated mode than that of Figure 2 of a method of the invention, which employs a container according to the first embodiment. Figure 4 is a schematic diagram in vertical cross section (not to scale) of a second embodiment of a container for use in the invention. Figure 5 (a) is a schematic diagram in vertical cross section (not to scale), showing a third embodiment of a container for use in the invention, and Figure 5 (b) is a schematic diagram showing how the embodiment Polished in 5 (a) can be sealed around a part of an article. Figure 6 conceptually illustrates a sterilizing unit adapted to cooperate with a container, as illustrated in Figures 5a and b, in an open configuration. Figure 7 illustrates the apparatus of Figure 7 in a closed configuration. Figure 8 shows the data in graphical form of Example 1, which uses a Tyvek ™ membrane. Figure 9 shows the data in graphical form of Example 3, which uses a Kimguard ™ membrane.

Figures 10, 11 show data in graphical form of Example 5. which shows how the concentration of water and peroxide, respectively, in the vessel, decreases as a function of time and flow of the outside stream. Figure 12 shows the data in graphical form of Example 6, and illustrates the decline in peroxide concentration in the vessel, as a function of time and humidity of the countercurrent air. Figure 13 shows the data in graphical form of Example 6, and illustrates the decline in peroxide concentration in the vessel as a function of time and peroxide concentration. The same numbers are used to identify parts in a drawing that has a function corresponding to the same part in another.

DESCRIPTION OF THE PREFERRED MODALITIES With reference to Figure 1, a first embodiment of a container 1 for use in the invention is shown. In this embodiment, the container 1 is in the form of a cylindrical cassette or chamber shown schematically in vertical cross section, but the container can be rectangular, any other suitable shape or formless. In the present example, the container 1 has a floor 3, a cylindrical wall 4, and a removable cover 5 that can be sealingly attached to the container 1, for example, by means of a threaded connection with intermeshing screw 7 and an intermediate seal 6. The seal 6 can be a ring in the case of a cylindrical chamber. The cover 5 is removable, so that an article 2 can be sterilized, can be placed in, or removed from the container 1. The article 2 is supported above the floor of the chamber by a perforated plate or gauze 10, which provides preferred support for article 2 at the contact points of the minimum matching surface area. In the present embodiment, the removable cover 5 has a large opening 8, which is covered by a semi-permeable membrane 9 sealed at its edges with the lid by means not illustrated in the drawing. By way of example, a membrane 9 can be bonded to the cover 5 by means of an adhesive or can be remotely sealed on the opening and held in place by a frame with suitable seals or the like. If desired, the membrane can be supported by an open mesh or perforated plate grid (not shown), to provide physical support. The cover 5 with the semipermeable membrane 9 constitutes an upper wall of the container. Desirably, the arrangement is such as to provide a substantial area of the wall of the container 1 that is semipermeable. Indicatively, in one example, the container 1 has a volume of approximately 5 liters, and the opening 8 has an area of approximately 450 square cm of semipermeable membrane. The semi-permeable membrane 9 in the present example is made of KIMGUARD ™, a lint-free three-layer laminated fabric, having an inner layer that is hydrophobic and resistant to bacterial penetration.

The two outer layers provide resistance and strength against abrasion. The cloth is permeable by virtue of the microscopic channels that provide a tortuous path that limits the passage of particles to those of less than 0.2 microns. This fabric allows the vapors of water and hydrogen peroxide to permeate through the channels of the fabric. The channels do not allow the passage of bacteria in the chamber and do not allow the nebulizer to pass out. Other fabrics and membranes which are permeable to water vapor and to hydrogen peroxide vapors and impenetrable by bacteria, for example, TYVEK ™ can be used. However, we have found that KIMGUARD ™ is 2-3 times more permeable to hydrogen peroxide vapor than TYVEK ™ under the conditions in which we use it. As will be discussed hereinafter, other semipermeable membrane materials, such as NAFION ™ (which is hydrophilic) and the like may also be employed. In the present embodiment, a tubular inlet 13 communicates with the interior of the container 1 via the inlet valve 11, which is also capable of sealing the enclosure. Upstream of the inlet valve, the present example has a connector 12. Referring to Figure 2, there is shown a flow chart schematically illustrating the method of the invention. The cover 5 of the container 1 is removed, an article 2 to be sterilized is enclosed inside the container 1, and the cover replaced, seals the article inside. The inlet valve 11 of the container 1 is placed in communication with the outlet of the aerosol 16 of a nebulizer 17 via a connector 18 adapted for connection to a connector 12 of the container 1. The nebulizer 17 is, for example, a nebulizer such as the one described in our copending application with reference to Figures 3 and 4 thereof, and operated at 2.4 MHz and has a liquid inlet 19, an air inlet 20, as well as an outlet of the nebulizer 16. A peroxide solution of hydrogen in water at a concentration of, for example, 35%, is fed from the reservoir 21 via the liquid inlet 19 to the nebulizer 17, which receives the air at its air inlet 20 from a fan or a bellows 22, which extracts the air of the atmosphere at 23. This air is not necessarily sterile, but it is desirably filtered, and if preferred, it could be sterilized, for example, by a hepafilter. The 35% hydrogen peroxide solution is nebulized in the air stream by the nebulizer 17, which produces an aerosol in which the finely divided particles or droplets of the 35% hydrogen peroxide solution are suspended as a nebulizer and which flows out of the nebulizer at the outlet of the aerosol 16. Typically, more than 90% of the drops of hydrogen peroxide in the nebulizer emanating from the outlet 16, are in the range of 1 -10 microns with the average size around of 3-5 microns ("microparticles"). With the valve 11 open, the aerosol of the nebulizer 17 is propelled into the interior of the container 1 by the fan 22. The droplets in the range of microns of hydrogen peroxide have a large air / liquid interface and at ambient or low temperatures (for example, below 60 ° C) and at atmospheric pressure, the water has a much higher vapor pressure than hydrogen peroxide and evaporates from the surface of the drop in preference to hydrogen peroxide. This water vapor is able to permeate through the semipermeable fabric 9 and does so with surprising speed. The removal of water vapor can be facilitated by blowing a stream of air from the "outside stream" onto the outer surface of the semipermeable membrane. The air stream from the outside stream removes the water molecules that reach the outer surface of the membrane 9 and facilitates the permeation from inside the container 1. As the water vapor leaves the chamber, more water evaporates from the surface of the vessels. drops of liquid in order to reestablish the partial pressure of water in the vapor phase in equilibrium with the liquid in the nebulized drops. The aerosol that enters the container 1 is unable to escape from the container, because the particle size is larger compared to the pore size of the membrane. The particles of the liquid become more concentrated as the water vapor is removed, and the more it evaporates from the drops, the concentration in the drops approaches 60% or more, the concentration of hydrogen peroxide. The drops are also reduced in diameter. As the nebulizer droplets become smaller, their diffusion coefficient increases exponentially. In our co-pending application, we have shown that these more concentrated particles, smaller in the presence of water, at relative humidities below about 80%, and preferably below 60%, are not only effective for sterilizing open exposed surfaces in a remarkably short time, but they are also able to penetrate between the surfaces that match, which is important for sterilizing instruments at support points, or in the case of lumens, at the connection points (if any). In contrast to the method described in our copending application, nebulization does not need in this invention to be subjected to energy of a kind and for a duration sufficient to vaporize the solvent in preference to the sterilizing agent, whereby the concentration of the agent in the Nebulized particles. The permeation through the semipermeable membrane 9 achieves a similar result, also without the use of vacuum, but in this case, without the expenditure of so much energy. Although the peroxide concentrations in the drops produced from the 30-35% peroxide solution typically approach 60% or more, it is not always necessary that such a high concentration of peroxide be reached. For example, in other preferred embodiments, an initial solution having a concentration of 10 to 15% peroxide can be nebulized and concentrated to about 45 to 60% peroxide. Any initial concentration of peroxide can be used, and is concentrated to any level up to the theoretical maximum achievable under the prevailing relative humidity and temperature conditions. Generally, in practical terms, a peroxide concentration of 10-15% to 30-35% is used as the initial solution, which is concentrated up to 45-60% or more in the nebulizer.

The nebulizer can be introduced into the container 1 continuously or intermittently, for example, 2 seconds on / 18 seconds off; or 5 seconds on / 15 seconds off; during a period of, for example, 2 minutes. The container 1 can then be isolated from the nebulizer by closing the valve 11. The removal of the vapor from the container through the semi-permeable membrane 9 can continue. As the concentration of hydrogen peroxide in the droplets increases, the proportion of hydrogen peroxide in the vapor in equilibrium with the droplets increases. Any peroxide vapor that vaporizes also permeates out of the chamber through the semipermeable membrane 9, and is removed in the air flowing out. Eventually, the aerosol droplets inside the container 1 decrease in size to a point where they become so small that they are capable of permeating the membrane 9, or vaporize completely and permeate the membrane like molecules. The sterile air, filtered by the membrane, permeates into the chamber as water vapor permeates outward. With the completion of the exemplified two minute cycle, the container 1 is isolated from the nebulizer 17 by means of the valve 11 (or if a non-return valve is used, the nebulizer can be turned off) and the external air flow continues for an additional period , for example, 8 minutes. The container 1 can then be disconnected at the connector 12 and removed for storage of the sterile article until required.

After removing the sterile article 2 for use, the container 1 can be reused. In the preferred embodiments, the permeation continues until substantially all of the remaining hydrogen peroxide in the container has evaporated and permeated outwardly. (By "substantially all" in this context, it means that the remaining peroxide has been reduced to a level of residue that is considered acceptable.) Thus, the remaining peroxide has vaporized and has a concentration below approximately 100 ppm, level in the which the amount of peroxide that condenses on the surface will be at a concentration of below about 1 microgram / square cm). In the less preferred embodiments, an air source, eg, sterile hot dry air, can be blown into the container 1 via the inlet valve 11 (by means not illustrated in Figure 2) for rapid peroxide removal and drying of article 2 before sealing the container. This drying air can be allowed to pass through the semipermeable membrane or a second outlet 15 provided with a valve or a non-return valve or the like can optionally be provided to allow a higher flow rate of the drying air through and out. of the device. However, it will be appreciated that a major advantage of using an outside air stream on the outside of the membrane to remove residual water and peroxide is that the air from the outside stream does not need to be sterile, while the air used to drying from the inside would need to be sterile, for example, filtered through a hepafilter. By preference, the outside air stream (and any air streams containing hydrogen peroxide), is fed through a catalytic destructor to return the innocuous peroxide before it is ventilated, or through a recovery unit that allows it to recover to reuse it. In each case, the valve 11 is closed before the termination of the sterilization. With reference to Figure 3, a more sophisticated flowchart for performing a method according to the invention is shown. This apparatus includes the parts described with reference to Figure 2 and those parts that perform the same function as previously described. In the embodiment illustrated in Figure 3, the container 1 enclosing the article 2 is placed with a larger external camera 14 having a removable cover 39 or other access means, such as a door. The nebulizer is supplied from the nebulizer 17 to the container 1 in the manner previously described, the feed line penetrates the wall of the external chamber 14. The air from the atmosphere is extracted by a fan or bellows 30, conditioned by conventional means (e.g. , heated to 45 ° C, and has the water removed at 20% RH) in a unit 31, and is conducted to the external chamber 14 in 36 and then directed tangentially as a fluid flow 25 adjacent to the surface of the semipermeable fabric 9 external to the container 1. This flow of air from the external stream leaves the external chamber 14 at 37 and is then optionally directed by the valve 32 and the non-return valve 33 to be recirculated through the conditioner 31, or to be treated in a catalytic destroyer 34 (desirable, but not essential), and ventilated at 35. An additional fan such as at 38, may optionally be provided on the side of the outlet 37 of the chamber 14. In a preferred variation of the embodiments described above, a NAFION ™ membrane is replaced by the KIMGUARD ™ fabric previously described, used for the semi-permeable membrane 9. NAFION ™ is a copolymer of tetrafluoroethylene and perfluoro-3,6-dioxa acid -4-methyl-octen-sulphonic. Such materials are hydrophilic and have very high hydration water. NAFION ™ is capable of absorbing 22% by weight of water. In this variation, absorption proceeds as a reaction with first order kinetics. The water molecules pass through the membrane and then evaporate into the surrounding air until equilibrium with external moisture is reached in a continuous process called pervaporation. A flow of the external stream of air on the outer side of the membrane, provides rapid removal of moisture from the external surface and accelerates the pervaporation process. Unlike simple permeation, where molecules simply diffuse through open pores, in pervaporation, the membrane is active by selectively removing molecules from one side of the membrane to the other, and can do so at speeds differentials for different types of chemical molecules.

In this specification, where the context allows references to a semi-permeable fabric or membrane, it includes fabrics or membranes suitable for pre-evaporation, as well as those only suitable for simple permeation, and references to permeation include references to pervaporation. n. Membranes other than those described and membranes may be used and may include membranes suitable for pervaporation. A second embodiment of a container for use in the invention is illustrated schematically in Figure 4, in which a cassette 40 is provided which is divided into two chambers by a semi-permeable membrane separation 9. The separation can be supported or reinforced. In the present example, the upper chamber 41 is the sterilization chamber corresponding to the container 1, and has walls 4, a floor 3 and a cover 5 that is removable to allow an article 2 to be sealed in the upper chamber. The article 2 is supported on an open mesh gauze or grid 10. A seal 6 between the cover 5 and the interior, prevents the entry of bacteria when the cover is in the closed sealed configuration. The cover 5 can be held in place in sealing engagement against the seal 6 by any suitable means, for example, clamps (not shown). The floor 3 defines a large opening 43 which penetrates from the upper chamber to the lower chamber, and which is covered by a semi-permeable membrane or fabric 9 which in the present example is a membrane of NAFION ™. The upper chamber 41 of the cassette has a tubular inlet 13 with a valve 11 and a connector 12, and optionally has an outlet tube 44 with the valve 45. The lower chamber 46 has an inlet 47 which is connected to an air source of the external current that is preferably associated with means (heaters, condensers or the like), to precondition it with respect to temperature and relative humidity and an air outlet 48. In use, this mode can be connected in a circuit similar to that previously described with reference to Figure 2. The interior of the upper chamber 41 may be connected to the nebulizer 17 via the inlet tube of the aerosol 9 and the valve 10 in a manner similar to the container of Figure 1. The outlet 45 if is present, it would be closed. The aerosol is unable to pass out of the upper chamber 41 through the membrane 9, and densities with high concentrations of the peroxide spray may accumulate within the chamber 41. When the concentration is sufficiently high, the chamber 41 may be sealed. The air inlet 47 in the lower compartment 46 is connected to the air source of Figure 2 at 36, while the outlet of the lower chamber would be connected to the circuit of Figure 2 at 37. The lower chamber 46 thus performs the function that in Figure 2 was performed by the larger chamber 14. A stream of air flowing to the lower chamber 46 at the entrance 47 through the lower chamber 46 and on the surface of the NAFION ™ membrane (exterior to the upper chamber 41) and outward via the outlet 48, rapidly removes the vapor from the lower chamber 46 and in turn, accelerates the vapor permeation out of the upper chamber 41. As the water vapor is removed, the particles from the mist of the peroxide solution in chamber 41 becomes more concentrated and becomes smaller. As the procedure continues, eventually the entire aerosol consists of a highly concentrated peroxide solution, the peroxide vaporizes, still at atmospheric pressure, at a rate similar to the rate of peroxide removal, until no aerosol remains and the article is dry and sterile. As previously discussed, after sufficient aerosol has been admitted and sufficient time has passed to achieve a desired disinfection / sterilization rate, hot air, dry air, or hot dry air can be allowed to circulate towards, through and out of the upper chamber to accelerate the reduction of residual peroxide, if any, to acceptable levels. A third highly preferred embodiment will now be described with reference to Figure 5a and 5b. In this embodiment of a container for use in the invention, the container is a bag 50 formed of a semipermeable membrane. The bag is desirably supplied open at one end 51, so that an article can be inserted therein. In the present example, the article to be disinfected is an ultrasound radiology probe 55, which has a long cable 53 with an electrical connector at the end of the remote cable to the probe. In such a case, it may be sufficient to place the part of the probe that requires sterilization. In the bag and to leave the connection cable of the probe and the electrical connector (or at least that portion of which does not need to be sterile), it extends out of the bag. Only a small portion of the cable that attaches to the probe is shown in the drawings. Once the part of the article is placed in the bag 50, the open end 51 can be sealed by any suitable means. In the present example, the open neck is wound around the cable and tape is placed in such a manner that the probe is sealed inside the bag, as shown in the sequence of Figure 5a and 5b. In the case where an article can be completely placed inside the bag, the neck of the bag can be placed, for example, by heat sealing or winding the end and holding the roll, by the use of sealants or removable putties, or another suitable means for preventing bacteria from entering the bag 50 after sterilization and before reopening. It will be understood that the bag 50 does not need to be made completely from the semi-permeable membrane and may include one or more panels of other suitable materials, such as a strong transparent clear waterproof film. The bag 50 can be of any suitable shape and can be reinforced to maintain a shape, or it can include a removable skeleton structure to aid in shape maintenance and handling, or it can be shapeless. Desirably, the bag is provided with an integral aerosol inlet opening 52, by means of which it can be attached to an outlet of the nebulizer, such as 16 in Figure 2, the opening is equipped with a non-return valve in a manner that the aerosol or fluid can only flow into the bag, or can have a self-sealing portion, through which a tap can penetrate for injection. The opening 52 can be provided with a protective cap or cap. In this embodiment, the bag 50 containing the sealed article within it, or the part of the article to be sterilized sealed therein, is placed in a console 60, conceptually shown in Figures 6, 7, provided with means adapted to connect the integral bag opening with a spray fountain. The unit illustrated in Figures 6, 7, is adapted to sterilize the two bags 50 at the same time, but units can be designed for one or any other number of bags. As shown in Figure 6, the console 60 has two chambers 14, in which the bags 50 can be suspended and closed by means of hinged doors 61 or the like. The console 60 includes a nebulizer 17 (not visible in Figure 6), the outlet of the aerosol 16 (not visible in Figure 6) of which, it is connected by means of a hose 62, and the connector 63 for interconnectable connection with the entrance opening 52 of the bags 50. The doors 61 (of which only one is illustrated in Figure 6), can then be closed to surround the bags 50. The circuits electrically connected to the control panel 64 of the console 60, provide that the nebulizer 17 is energized according to the selected program, whereby an aerosol containing, for example, 35% hydrogen peroxide as the nebulizer, is supplied to the bag 50 via the hose 62 and the connector 63 at a predetermined speed and duration (for example, intermittently, for example 2 seconds on, 5 seconds off, for a period of, for example, 2 minutes). The console 60 and the cover of the hinged door 61 cooperate to provide an isolated environment surrounding the connected bag 50 and corresponding according to the external chamber 14 of Figure 3. The control panel 64 also provides air circulation of the outside stream on the outer surface of the bag 50, to remove water vapor and hydrogen peroxide vapor that permeates outwardly. For example, the air can be removed from the back of the unit by a fan, passed over a heating element 65 and is restricted by the design of the chamber to flow over the surface of the bag. The air can then be vented to the top (if the unit is designed for operation in a gas cabinet) or is directed through a catalytic peroxide destructor before venting (not visible in the drawing). Figure 7 shows the conceptual unit of Figure 6 with the doors closed.

EXAMPLE 1 A camera similar to that shown in Figure 1, but with a rectangular shape, was provided with a TYVEK ™ fabric membrane, the chamber has a volume of 0.5 liters and the membrane has an area of 110 cm2. The chamber was placed in the external chamber 14 of the circuit of Figure 3, which was operated under the following conditions: Initial concentration of hydrogen peroxide: 35% Cassette temperature: nominal 50 ° C, (actual 49.5- 51.0 ° C) Nebulizer power: 10 w Misting speed: 2 g / minute Aerosol flow speed: 2 m / second Misting duration: 2 minutes Working cycles A. 2 seconds on / 10 seconds off B. 5 seconds on / 15 seconds off C. 10 seconds on and 10 seconds off Air flow rate of outside air stream flow: 4.5 L / minute.

The nebulizer was injected into the chamber for the duration of the two minute nebulization, with the nebulizer being operated in accordance with work cycle A. At the conclusion of two minutes, the cassette was sealed, and the air passed as a flow countercurrent on the outer surface of the membrane for 8 minutes (total run, 10 minutes). During the two minutes of nebulization (spray injection) and the subsequent 8 minutes, the concentration of water vapor and hydrogen peroxide vapor in the sterilization chamber was verified. The concentration of water vapor and hydrogen peroxide in the air of the outside stream was also verified (in the practice of the invention, it may be preferred to run the flow of the outside stream from an earlier or later stage in the cycle). Figure 8 graphically shows how the concentration of the water vapor (expressed as relative humidity) and the hydrogen peroxide vapor (expressed as ppm), varies with time within the container 1 during the 10 minute period. The temperature was also verified and remained at 50 ° C with only a minor variation. With reference to Figure 8, it can be seen that the concentration of water vapor rises rapidly, reaching about 40% humidity (over the course of about 3.5 minutes), and subsequently declines to about 9 minutes, then drops abruptly. The hydrogen peroxide vapor also has a maximum rapidly to slightly above 3000 ppm within the container 1, during the course of the first three minutes (time at which the nebulization has ceased), and subsequently declines almost exponentially to the 9 minutes, then drops abruptly to about 9 minutes to less than about 100 ppm. It is believed that the rapid initial rise in peroxide vapor and water concentrations indicates a rapid equilibrium between the partial pressure of the water vapor in the container and the water in the nebulizer, the maximums are due to the concentration of peroxide that reaches the point where the peroxide and water evaporate at a constant ratio, and the decline is due to the elimination of the decreasing amounts of water remaining within the chamber. After 10 minutes, less than 1 microgram / cm2 can be detected on the surface of the articles taken from the camera. Very similar results were obtained with the work cycles B and C, but longer water removal periods were required.

EXAMPLE 2 Example 1 was repeated, but using a flow velocity of the outside air of 12.0 L / minute. The results were very similar in terms of the observed profile, but the elimination of the water and the peroxide occurs much more quickly, the peroxide is substantially eliminated within the course of about 7 minutes.

EXAMPLE 3 In this example, the procedure of Example 1 was repeated under the same conditions as Example 1, except that the TYVEK 9 membrane was replaced with a KIMGUARD ™ 9 membrane. The results are shown in Figure 9.

EXAMPLE 4 In this example, the procedure of Example 1 was repeated under the same conditions as Example 1, except that the TYVEK 9 membrane was replaced with a NAFION ™ membrane. The results obtained were very similar to those obtained with TYVEK and KIMGUARD ™.

EXAMPLE 5 Figure 10 shows how the water vapor removal rate of the vessel changes over time for different air flow velocities of the outdoor stream. In this Example, a KIMGUARD ™ 9 membrane was used under the conditions as in Example 1. The faster the air flows from the outside stream, the faster water is removed, but this is subject to the law of declining returns. . Although there was a significant benefit in increasing air flow from 0 to 4.5 m / second, there was less additional benefit going from 4.5 to 9.0 m / second and even less benefit going from 9.0 to 12.0 m / second. Figure 11 shows the corresponding effect of the extraction rate of hydrogen peroxide (initial concentration of 35%). The amount of hydrogen peroxide declines rapidly, and removal is greatly improved by the air flow, but the benefit of increasing the air flow velocity above 4.5 m / second is small, and above 7.5 m / second It is marginal. Very similar results were obtained with TYVEK or NAFION membranes.

EXAMPLE 6 Example 1 was repeated using KIMGUARD as the fabric of the membrane, but varying the concentration of the hydrogen peroxide solution fed to the nebulizer. The air flow velocity of the external current was 3 m / second. The effect on the% RH and the concentration of the peroxide in the vessel 1 as a function of time is shown in Figures 12 and 13, respectively. The hydrogen peroxide solution of 35% or less would not be classified as irritant to the skin in rabbits by the criteria of E.U.A. (ECETOC, 1996), and is capable of handling without special precautions. Figures 12, 13 show that initial peroxide concentrations below 20% can also be used, but at the cost of somewhat longer elimination times.

EXAMPLE 7 The size of the nebulized particle in the aerosol emanating from the aperture 45 when membrane 9 was a KIMGUARD ™ semipermeable membrane, was compared to the particle size when membrane 9 was from NAFION ™. It was found that the particle size distribution changes to smaller particles as a function of the velocity of the external flow of air on the outside of the semipermeable membrane. Tables 1 to 4 exemplify the effect. Table 1 shows the particle size distribution of a nebulizer of an ultrasonic nebulizer fed with a 30% hydrogen peroxide solution at various temperatures.

TABLE 1 Table 2 shows the data of the size of the nebulized particle when a NAFION membrane was used with several air flow velocities on the outer side.

TABLE 2 Table 3 shows the particle size data of the nebulizer when a KIMGUARD membrane was used at various air flow velocities on the outer side.

TABLE 3 EXAMPLE 8 Table 4 illustrates the effectiveness of the system biocide using a KIMGUARD bag as the container. Microbiology was described in our co-pending application. The bag has a surface area of 644 square cm. Air with a HR = 20%, was blown on the outside of the bag to 12 m / second through the exposure time. A log 6 reduction in the bioburden was obtained in the course of 5 minutes, by nebulizing a 10% peroxide solution and in the course of 2 minutes nebulizing a 30% peroxide solution. The residual peroxide concentrations at the conclusion were below 250 ppm. The residues on the surface of the article were below 1 microgram per square cm.

O CC a < OR EXAMPLE 9 (Waste) Example 2 was repeated with different work cycles and using samples of various materials under the conditions shown below. Residual peroxide levels were then measured. Table 5 shows the residual peroxide levels in the materials selected to be representative of those commonly found in the DU probes. In this example: The supply was 1 minute in total. The exposure time was 2 minutes. The drying / aeration time was 2 minutes. The total elapsed cycle time was 5 minutes.

TABLE 5 * below the detection level of the test, ** Acrylonitrile-butyrene-styrene.

Although the invention has been described herein with reference to hydrogen peroxide as the sterilizing agent, the invention may utilize other peroxides, peroxy compounds or complexes of any of these. Other kinds of biocides may be used, including non-exclusively, halogenated biocides, phenolic biocides and biocides of a quaternary compound, and it may be advantageous to use solvents other than water. Similarly, although the invention has been exemplified hereinbefore with reference to the initial solutions having 35% peroxide, other initial concentrations may be used, although concentrations between about 20% and 35% are preferred. The container having a wall of which at least a part is a semipermeable membrane or fabric, may be of any suitable shape and design with respect to the requirements of the process described herein, and may be sealed in any impenetrable manner for microorganisms . Other semipermeable membranes or fabrics may be selected based on the teachings provided herein. The container can be permanently connected to the nebulizer circuit or it can be able to be connected and disconnected by means of a tube and bobbin connection, by suitable connectors or other means. The apparatus can be made of any suitable material and the process can be verified by instruments that by preference, verify the external flow more than the inside of the container, but can check the conditions inside the container if desired. The nebulizer does not need to be ultrasonic, and any other means to form an aerosol can be used, including sprays, jets and other devices. It is conceivable that the peroxide can be pre-packaged and stored as an aerosol in the aerosol container and can be admitted from the aerosol container. It is also considered that cassettes incorporating an ultrasonic transducer can be used to generate an aerosol in situ within the enclosed container, which would be provided with electrical connections to the outside to provide energization and control. Although it is highly preferred to employ an aerosol to perform the sterilization, the concept of the invention would also be applicable to processes in which a predetermined solid or liquid sterilizer, such as peroxide, is admitted to the container as a vapor or as a solid or liquid that vaporizes later. Several such procedures have been described (e.g., in US 6451254, US 6673313, US 6656426), all of which involve concentrating a hydrogen peroxide solution by lowering the pressure to preferentially evaporate the water and remove water to through a vacuum pump before the vaporization of the solution. The principles taught herein can be applied to concentrate the peroxide in such processes with steam by permeation or pervaporation through a membrane, without the need for pressure reduction. However, the benefits (described in our co-pending application) of using the aerosol of the invention would be lost as the sterilant is lost. If a lumen or device such as an endoscope having one or more lumens is to be treated, the aerosol can be directed through the lumen, as well as around its exterior and for that purpose, suitable connections or manifolds can be provided, for example, in the chamber 41 of the cassette of Figure 4. Although the method has been described herein and exemplified with reference to the examples, wherein the entire procedure is performed in a container, it will be understood that the steps of the procedure can be performed in different ways. cameras. For example, the step of concentrating the nebulizer (and / or a vapor) can be carried out in a chamber without reducing the pressure, and the step of contacting the article with the concentrated nebulizer (and / or vapor) can be carried out. in a different container.

The invention can be incorporated in other forms and all of such variations that will be apparent to those skilled in the art from the teachings herein are considered to be within the inventive concept described herein.

Claims (34)

1. NOVELTY OF THE INVENTION
2. CLAIMS 5 1. A method for disinfecting or sterilizing an article or part of the article, comprising the steps of (1) enclosing the article or part of the article.
3. «Article inside a container having a wall, in which at least one part is a semi-permeable fabric or membrane; (2) introducing a quantity of vaporizable biocide into the interior of the container; (3) the semipermeable web or membrane is selected to allow the biocide to pass from the interior to the exterior of the container as a vapor at atmospheric pressure, and to provide a barrier against the entry of microorganisms; (4) allow the biocide to exit the container through the membrane, while at or above atmospheric pressure, (5) expose the article or part 5 of the article to the biocide for a sufficient time to disinfect or sterilize Article. 2. The method according to claim 1, further characterized in that the biocide is introduced into the container in step 2 as a solution. 3. The method according to claim 1 or claim 2, further characterized in that the biocide is introduced into the container in step 2 as a nebulizer.
4. 4. - The method according to claim 1 or claim 2, further characterized in that the bokid is introduced into the container in step 2 as a vapor.
5. 5. The method according to claim 1 or claim 2, further characterized in that the bokid is introduced into the container in step 2 as a liquid.
6. 6. The method according to any of the preceding claims, further characterized in that the semipermeable fabric or membrane is selected to allow steam to pass from the interior to the exterior of the container, while preventing the entry of microorganisms.
7. 7 .- The method according to any of the preceding claims, further characterized in that a fluid is directed to flow adjacent to the outside of the membrane, for rapid removal of steam from the interior side.
8. 8. The method according to claim 7, further characterized in that the fluid is air.
9. 9. The method according to claim 7 or 8, further characterized in that the fluid is air conditioned with moisture.
10. 10. The method according to any of the preceding claims, further characterized in that the biocide is a solution of hydrogen peroxide in a solvent.
11. 11. The method according to claim 10, further characterized in that the solvent is water.
12. 12. - The method according to any of the preceding claims, further characterized in that the membrane is selected from woven and nonwoven fabrics, sheets or films or combinations thereof in a single layer or multilayer structure and is hydrophobic or hydrophilic .
13. 13. A method for disinfecting or sterilizing an article or part of the article comprising the steps of (1) enclosing the article or part of the article within a sterilization chamber, (2) admitting a biocide solution comprising a biocide dissolved in a solvent, to a pre-chamber that communicates with the sterilization chamber; the prechamber has a wall or part thereof comprising a fabric or semi-permeable membrane selected to allow the vapor to pass from the interior to the exterior of the prechamber, while providing a barrier against the entry of microorganisms and against the exit of the particles of the pre-chamber. nebulized (3) concentrating the biocide in the prechamber by removing the solvent at atmospheric pressure, to form a concentrated biocide, (4) introducing the concentrated biocide as a liquid or vapor or a combination thereof from the second container to the first; and wherein steps (2) - (5) are performed at or above atmospheric pressure.
14. 14. The method according to claim 13, further characterized in that the biocide is introduced into the container in step 2 as a solution.
15. 15. - The method according to claim 13 or 14, further characterized in that the biocide is introduced into the container in step 2 as a nebulizer.
16. 16. The method according to any of claims 13 to 15, further characterized in that the biocide is introduced into the container in step 2 as a vapor.
17. 17. The method according to any of claims 13 to 16, further characterized in that the biocide is introduced into the container in step 2 as a liquid.
18. 18. The method according to any of claims 13 to 17, further characterized in that the semipermeable fabric or membrane is selected to allow steam to pass from the interior to the exterior of the container, while preventing the entry of microorganisms.
19. 19. The method according to any of claims 13 to 18, further characterized in that a fluid is directed to flow adjacent to the outside of the membrane for rapid removal of steam from the interior side.
20. 20. The method according to claim 19, further characterized in that the fluid is air.
21. 21. The method according to claim 19 or 20, further characterized in that the fluid is air conditioned with moisture.
22. 22. - The method according to any of claims 13 to 21, further characterized in that the biocide is a solution of hydrogen peroxide in a solvent.
23. 23. The method according to claim 22, further characterized in that the solvent is water.
24. 24. The method according to any of claims 13 to 23, further characterized in that the membrane is selected from woven and non-woven fabrics, sheets or films or combinations thereof, in a structure with a single layer or with multiple layers and it is hydrophobic or hydrophilic.
25. 25. The method according to any of claims 13 to 24, further characterized in that solvent is removed from the prechamber by providing the prechamber with a wall, of which at least a part is a semipermeable fabric or membrane chosen to allow the steam passes from the interior to the exterior of the container, while providing a barrier against the entry of microorganisms and against the exit of the particles from the mist; and allowing the solvent to be removed from the second container as a vapor, with reference to the biocide.
26. 26. The method according to any of claims 13-25, further characterized in that the biocide solution is admitted to the prechamber as a nebulizer.
27. 27. The method according to any of claims 13 to 26, further characterized in that the elimination of the solvent from the prechamber is accelerated, directing a gas or gas stream with controlled humidity in contact with the outside of the wall membrane. of the prechamber.
28. 28. The method according to any of claims 13 to 27, further characterized in that the elimination of the solvent from the prechamber continues until the ratio of solvent to vapor of biocide reaches an equilibrium ratio and / or the ratio of the solvent to the Biocide in the remaining mist drops reaches a balance.
29. 29. The method according to claim 28, further characterized in that the prechamber is isolated from the sterilization chamber until one or more equilibrium ratios are reached.
30. 30. The method according to any of claims 13 to 29, further characterized in that the biocide is introduced to the prechamber as a liquid in the form of a nebulizer.
31. 31. The method according to any of claims 13 to 30, further characterized in that the biocide is hydrogen peroxide.
32. 32. The method according to any of claims 13 to 31, further characterized in that the biocide is introduced to the prechamber as a liquid having a concentration of less than 35% and in the form of a nebulization.
33. 33.- The method according to any of claims 13 to 32, further characterized in that the biocide is introduced into the sterilization chamber as a liquid having a concentration of more than 55% and in the form of a nebulization.
34. 34.- The method according to any of claims 13 to 33, further characterized in that the biocide is introduced into the sterilization chamber as a vapor of constant concentration and at an atmospheric pressure or higher.