MX2008001782A - Apparatus for concentrating a nebulant - Google Patents

Abstract

Apparatus for concentrating a nebulant comprising a nebulant flow conduit and a counter-flow conduit, or preferably, a plurality of alternating nebulant flow conduits and corresponding counter-flow conduits eg in layered or coaxial arrangement, and wherein at least a portion of the nebulant flow conduit and said counter-flow conduits define respective opposed sides of agas permeable membrane. In use a nebuliser is in communication with the nebulant flow conduit and the nebulant flow and counter-flow are in the same or opposite directions and act to concentrate the amount of active in a droplet eg from 35wt%to 60wt%hydrogen peroxide in water to disinfect and/or sterilize an article.

Description

APPARATUS TO CONCENTRATE A NEBULIZER FIELD OF THE INVENTION This invention relates to a method and apparatus for concentrating aerosols, such as those that can be used, for example, to disinfect or sterilize a surface. The method and apparatus are particularly suitable for disinfecting or sterilizing medical instruments, but are not limited to that use.

BACKGROUND OF THE INVENTION The present application incorporates as a reference all the co-pending applications of the applicants AU2005904181, AU 2005904196 and AU 2005904198. As indicated in these co-pending applications, sterilization procedures and apparatuses that set out the following criteria are highly desirable: (a) to avoid the need for vacuum (b) to avoid the need for a rinsing step (c) to avoid the need for temperatures above 60 ° C. Many of the prior art methods employ vacuum and / or rinsing steps. These have the effect of increasing the complexity and cost of the apparatus required, and can prolong the time of the disinfection or sterilization process considerably (which means more downtime for expensive medical instruments). The use of high temperatures can also increase the complexity and cost of sterilization instruments, but more importantly, it can damage many materials. It is desired to provide disinfection methods and apparatuses that meet these criteria, and at the same time obtain the greatest possible efficiency in destruction of pathogens, especially when dealing with occluded, equalized and lumen surfaces. It is advisable that the disinfection methods use hydrogen peroxide. Hydrogen peroxide at low concentrations is safe to transport, sell and handle and is extremely known, with few or no regulatory barriers to its use. However, there are problems with those methods which require hydrogen peroxide at a high concentration as a starting material. For example, commercial steam and plasma processes use as a starting material 60% peroxide irritant and corrosive solutions which require special packing and handling precautions. When hydrogen peroxide is used in the form of small droplets (sprayed, ultrasonically nebulized, etc.), the particles tend to deposit as droplets on surfaces and the residual layer of peroxide is a potential problem. Medical instruments, food packaging and other disinfected items need to be stored dry to avoid repeated contamination. Importantly, surgical instruments should not contain residual peroxide at levels above 1 microgram / cm2. However, the removal of residual peroxide is very difficult.

It requires either washing, which introduces the associated problems previously discussed in the co-pending applications with respect to liquid systems, prolonged periods of drying at high temperatures (which completely negate any advantage arising from rapid down times and low process temperature) or it requires the use of catalase or other chemical means to decompose the peroxide (which requires even drying and creates a series of problems with residual chemicals left in the instruments) or the use of vacuum. Therefore, it is advisable to provide a system that uses the minimum possible amount of peroxide to obtain a desired effect. Any discussion of the prior art throughout the specification, in no way should be considered as an admission that said prior art is widely known or is part of the general knowledge common in the field.

OBJECTIVES OF THE INVENTION It is an object of the invention to provide improved methods and apparatus for disinfecting or sterilizing medical instruments, which avoid or improve at least some of the disadvantages of the prior art. It is an object of the preferred embodiments of the invention to provide improved methods and apparatus capable of concentrating and improving the properties of an aerosol. Unless the context clearly requires otherwise, throughout the description and claims, the words "comprise", "comprising", and the like will be interpreted in an inclusive sense as opposed to an exclusive or exhaustive sense; that is, in the sense of "includes, but is not limited to".

BRIEF DESCRIPTION OF THE INVENTION According to a first aspect, the present invention provides an apparatus for concentrating a nebulizer comprising: A nebulizer flow conduit; A counterflow conduit; and wherein at least a portion of said nebulizer flow conduit and said counterflow conduit define respective opposite sides of a gas permeable membrane.

According to a second aspect, the present invention provides an apparatus for concentrating a nebulizer comprising: A plurality of alternating nebulizer flow conduits and corresponding counterflow conduits; and wherein at least a portion of each said nebulizer flow conduit and an adjacent counterflow conduit define respective opposite sides of a gas permeable membrane. The alternating nebulizer flow conduits and counterflow conduits may be in a layered configuration. Alternatively, they may be in a coaxial, concentric tubular arrangement. Each nebulizer flow conduit comprises an inlet and an outlet. Each counterflow conduit comprises an inlet and an outlet.

Preferably, the flow of nebulizer and counterflow are in opposite directions. However, they may be in the same direction, or any other direction, for example, perpendicular flows. According to a third aspect, the invention provides an apparatus for concentrating a nebulizer comprising: A nebulizer flow conduit; At least two backflow ducts; and wherein at least a portion of said nebulizer flow conduit and said counterflow conduits define respective opposite sides of gas permeable membranes.

According to a fourth aspect, the invention provides an apparatus for concentrating a nebulizer comprising: At least two nebulizer flow conduits; A counterflow conduit; and wherein at least a portion of said counterflow conduit and said nebulizer flow conduits define respective opposite sides of gas permeable membranes. According to a fifth aspect, the present invention provides a method for concentrating a nebulizer, comprising the steps of: (1) providing a nebulizer flow of an active in a solvent and having a first active: solvent ratio in a first side of a gas permeable membrane; and (2) providing a counterflow of a gas on a second side of the gas permeable membrane whereby said ratio on the first side is increased to a second active: solvent ratio greater than the first active: solvent ratio. The concentrated nebulizer is preferably used to disinfect and / or sterilize an article. The nebulizer preferably is a water nebulizer and a biocide. Preferably, the biocide is hydrogen peroxide. The first solvent to solvent ratio is preferably about 30% by weight.

The second active: solvent ratio is preferably about 70% by weight. The backflow of gas is provided at a rate and for such a time that the second ratio is not capable of another increase. Preferably, the gas is air, preferably air conditioning with moisture. The semi-permeable fabric or membrane can be a woven fabric, or non-woven, or it can be a sheet or film or a combination thereof and can be a single layer or a multi-layer construction. The term "semi-permeable membrane" is used in the present when the context permits, to include all those fabrics and membranes having the selected properties. The semi-permeable membrane can be hydrophobic or hydrophilic in nature. The semi-permeable membrane is selected to ensure that the particles of the nebulizer can not penetrate initially. In this specification, where the context permits, references to a semi-permeable fabric or membrane include suitable fabrics or membranes for pervaporation, as well as those only suitable for simple penetration, and references to penetration include references to pervaporation. Membranes other than those described may be used and may include membranes suitable for pervaporation.

In a highly preferred embodiment, a peroxide solution having an initial concentration of at least 6%, preferably 20% -35%, and 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 scale scale distribution of about 1-10 microns are suspended in an air stream. As used herein, the term "nebulizer" describes droplets of liquid (ie, finely divided liquid particles) entrained in a gas stream. A system of liquid droplets entrained or suspended in a gas is an "aerosol". Without intending to be limited to theory, it is believed that as water vapor penetrates through the membrane, the water evaporates from the nebulizer droplets in order to restore the equilibrium vapor pressure inside the duct. Nebulizer flow. Continuous evaporation from the droplets results in the peroxide solution in the nebulizer becoming more concentrated, and the droplets reducing in size. These smaller particles of more concentrated nebulizer are significantly more effective as a sterilant than the hydrogen peroxide vapor of the prior art, possibly because a much higher concentration of sterilant can be obtained per unit volume than with steam and is more effective than the sterilizers and peroxide nebulizer processes of the prior art.

The air that enters the nebulizer flow conduit is sterile because the membrane can not be penetrated by microorganisms. According to a sixth aspect, the invention provides a method according to any of the preceding aspects, wherein the semi-permeable membrane is selected to remove one or more vapors through a pervaporation process. Although the invention is described herein with reference to hydrogen peroxide as the biocide, the invention can be applied in the same way when the biocide is another peroxide or peroxy compound, or it can be used with other vaporizable biocides or biocides when dissolved in solvents. suitable (which do not need to be aqueous). Further, although the introduction of the biocide as an aerosol is more preferred, in less preferred embodiments, the biocide can be introduced as a vapor and the vapor subsequently removed at atmospheric pressure by an adjacent external air stream (or other fluid). to the outside of the membrane. The introduction of the biocide as an aerosol is preferred to a greater extent because much higher initial biocide densities can be obtained per liter of container than with a vapor. The copending 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.

According to a seventh 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 first container having a wall of which at least one part is a semi-permeable fabric or membrane; (2) The semi-permeable fabric or membrane is selected to allow the vapor to pass from the inside to the outside of the container while providing both a barrier against the entry of microorganisms and against the exit of particles from the nebulizer; (3) Admit a biocidal solution comprising a biocide dissolved in a solvent in a second container; (4) Concentrate the biocide in the second container by removing solvent, to form a concentrated biocide; (5) Introduce the concentrated biocide as a liquid or a vapor or a combination thereof from the second container to the first; and Where steps (4) - (5) are performed at or above atmospheric pressure. In preferred embodiments according to the sixth aspect, a solution of hydrogen peroxide in water, for example, of a concentration at 35% is first concentrated as a nebulizer in a chamber by the removal of water through a membrane at atmospheric pressure. . The concentrate nebulizer is subsequently admitted to another chamber, which conveniently is a bag or other container having a semi-permeable membrane that is defined as a wall or part thereof which is subsequently sealed. This allows the article to be sterilized and stored sterile in the second container and allows the removal of residual hydrogen peroxide and water. Preferably, the invention provides in particular, a nano-nebulizer having 90% of particles in the 3-5 μm scale and a peroxide concentration of > 70% by weight and a water concentration less than 30% by weight. According to an eighth aspect, the invention consists of a nano-nebulizer comprising a solution of hydrogen peroxide suspended in finely divided form, wherein the liquid particles have a concentration of more than 60% by weight of hydrogen peroxide, and a diameter average of less than 1.0 microns. Preferably, the drops have an average diameter of less than 0.8 microns. It will be appreciated that in the aerosol systems of the prior art, the liquid peroxide particles have had a concentration of less than 35% by weight of hydrogen peroxide and an average diameter exceeding 2 microns. The relationship between particle size and particle dropping velocity in an aerosol is not linear, and thus a small reduction in particle diameter greatly increases the suspension stability as well as the increase of the total surface area of the gas / liquid interface.

Conveniently, the nebulizer according to the seventh aspect has a peroxide density (grams of hydrogen peroxide / liter of aerosol) much greater than the peroxide density of a vapor just below its saturation limit at a temperature and humidity corresponding.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a reproduction of a figure of US 4,797,255 which shows (curve A) how the boiling point of a water / peroxide mixture changes with the concentration at atmospheric pressure and (curve B) how the composition of the gas changes; Figure 2 is a diagram of a first simple embodiment of the present invention; Figure 3 is a diagram of a sterilization apparatus showing the preconcentrator of the present invention; Figure 4 is a more detailed schematic diagram of a sterilization apparatus showing the preconcentrator of the present invention; Figure 5 shows another embodiment of the present invention; Figures 6A and 6B show nebulizer and counterflow flow patterns in one embodiment of the present invention; Figures 7A and 7B show the plates that can be used to separate semi-permeable membranes in those embodiments of the present invention using stacked dispositions; Figures 8A and 8B show results of a membrane concentrator of the present invention; and Figure 9 shows an ultrasonic probe in a disinfectant arrangement with a nebulizer of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED MODALITIES The invention will now be described in the context of sterilization, but it will be appreciated that the preconcentrators and preconcentration methods of the present invention can be used in a variety of fields where concentrated nebulizers are desired, eg, drug delivery, paint / printing, food preparation, manufacturing of materials and the like. For example, a number of such procedures have been described (US 6451254, US 6673313 and US 6656426) which all involve the concentration of a hydrogen peroxide solution by reducing the pressure to preferably evaporate water and remove the water through a Vacuum pump before vaporizing the solution. The general preconcentration method of the present takes place in the context of the following, and can be seen with reference to figure 3. An article to be sterilized 1 is placed in a sterilization chamber 2. The sterilization chamber 2 can be any suitable container, but advantageously is a bag made of a semipermeable membrane, or a sealed container having a window of a semi-permeable membrane 3. A preconcentration chamber 4 of the present invention is connected upstream of the sterilization chamber 2. The sterilization chamber 2 and preconcentrator 4 are connected so that the flow between the preconcentrator and sterilization chamber can be opened or closed by means of a valve 5. An ultrasonic nebulizer 6 is connected upstream of the pre-concentrator chamber. A solution of hydrogen peroxide having an initial concentration of preferably about 30-35% is nebulized in an ultrasonic nebulizer. The nebulizer 6 can be fed with sterilizing solution in a continuous or intermittent manner from a volumetric delivery 7, for example, while maintaining a predetermined liquid level in the nebulizer, or it can be provided with a single injection metering system, for example, a cartridge that provides sufficient solution for one or a plurality of sterilization cycles. Alternatively, a pre-packaged sterilizing solution can be provided in a capsule which can be placed in a nebulizer adapted for the capsule to be in contact with the ultrasonic transducer of the nebulizer. In this case, means are provided for piercing the capsule so that it can release the solution as a nebulizer. In another modality, the sterile solution can be provided in a capsule having an integral ultrasonic transducer adapted to be energized through contacts that extend through the capsule wall when the capsule is inserted into the nebulizer. The nebulizer 6 does not need to be ultrasonic, and any other means can be used to form an aerosol including sprays, jets, and other devices. It can be envisaged that the peroxide can be pre-packaged and stored as an aerosol in an aerosol container and can be admitted from the aerosol container. It is also contemplated that cassettes incorporating an ultrasonic transducer may be used to generate an in-situ aerosol inside the enclosed container which may be provided with electrical connections to the outside to provide energization and control. The nebulizer 6 preferably operates at around 2.4 MHz to form an aerosol typically with more than 90% of the droplets having between 1 and 10 μm in diameter, with the average size being approximately 3-5 μm in diameter ("microparticles" ). Although the present invention has been described with reference to nebulization by means of an ultrasonic nebulizer, it will be understood that other means for nebulization may be employed including sprays, jet nebulizers, piezoelectric nebulizers, and similar nebulizer generating devices. As described in the co-pending application (PCT / AU99 / 00505), smaller particles can be obtained by including a surfactant, for example an alcohol, in the sterilizing solution at the time of using the ultrasonic nebulization. It is not necessary for an ultrasonic nebulizer to operate continuously and in preferred embodiments of the invention, the nebulizer is turned on and off cyclically, (or at irregular intervals) operating, for example, at about 20 seconds per minute. The aerosol or nebulizer of microparticles is subsequently propelled in the preconcentrator 4 by means of a fan 8 upstream of the nebulizer 6. The microparticles formed by the nebulizer 6 are entrained in a gas stream, which in the preferred embodiment, is air. It is an important advantage of the preferred embodiments of the invention with respect to the prior art that a sterile filtered air source is not required. In contrast, the invention is capable of extracting non-sterile air from the sterilization chamber, and sterilizing it while recirculating it in use. However, if preferred, aseptic filtered air may be used. The gas stream is not necessarily air, and for example, it can be an inert gas such as nitrogen, or argon; or it can be oxygen or ozone. In general terms, the preconcentrator 4 works by exposing the aerosol droplets to one side 10 of a semi-permeable membrane 9 while a stream of air moves through the other face 11 of this semi-permeable membrane. This leads to preferential evaporation of water from the aerosol droplets, causing them to become more concentrated with respect to hydrogen peroxide. As a result of the preferential evaporation of water, the aerosol droplets within the preconcentrator 4 become more concentrated with respect to the hydrogen peroxide with the concentrations approaching 60% or more. Preferably, the water continues to evaporate from the droplets until this maximum concentration of hydrogen peroxide is reached, after which the peroxide and water evaporate in a fixed equilibrium ratio. Once formed, the highly concentrated small drops then make contact with the item that will be sterilized. There are two possible preferred modes of operation of the preconcentrator: In the first operating mode, which is a batch-based concentration process, the path between the concentrator 4 and sterilization chamber 2 is turned off and an aerosol of a peroxide solution of 35% hydrogen in water with droplet sizes between 1 and 10 μm is taken to the pre-concentrating chamber 4. Subsequently, the pre-concentrating chamber is isolated (when both valves 5 and 12 are closed) and the aerosol in the pre-concentrator 4 is subsequently concentrated. The concentration in the preconcentrator occurs until the maximum concentration of peroxide is reached, after which the peroxide and water evaporate in a fixed proportion of equilibrium. Once this maximum concentration is reached, the path between the preconcentrator and sterilization chamber is opened upon opening the valve 5 and the concentrated nebulizer is introduced into the sterilization chamber 2.

In the second alternative operating mode, which is a continuous concentration method, the path between the preconcentrator 4 and the sterilization chamber 2 is left open. An aerosol of a 35% hydrogen peroxide solution in water with droplet sizes between 1 and 10 μm enters the preconcentration chamber 4 and passes continuously through the preconcentrator with fan drive 8. As the droplets spray passes through the pre-concentrator 4, the water is preferably removed. The residence time of the drops in the preconcentrator is such that the maximum possible concentration of peroxide is reached by the time they leave the preconcentrator. The nebulizer can be introduced into the preconcentrator 4 continuously or intermittently, for example, two seconds on / 18 seconds off; or 5 seconds on / 15 seconds off; for a period, for example, 2 minutes. However, regardless of whether batch-based mode a) or continuous mode b) is used, or even if some combination of continuous or batch-based modes is used, the aerosol drops that come out of pre-concentrator 4 and enter the chamber of sterilization 2 are at their maximum concentration of hydrogen peroxide that can be reached. As the concentration of hydrogen peroxide in the droplets increases, the proportion of hydrogen peroxide in the vapor in equilibrium with the droplets increases.

Once the concentrated nebulizer is introduced into the sterilization chamber 2, it makes contact with the article that will be sterilized 1 and acts on the pathogens on the surface. The sterilization chamber 2 can be subsequently sealed from the pre-concentrator 4. Because the peroxide concentration is at a maximum, no further concentration of the peroxide solution occurs in the sterilization chamber 2. Any evaporation in the sterilization chamber occurs so that the peroxide and water evaporate in a fixed proportion of equilibrium. Subsequently, the concentrated biocide is allowed to make contact with the article that will be sterilized. The item that will be sterilized can be stored in the sterilization chamber until needed. This also allows the removal of residual hydrogen peroxide and water. To expand each of the steps, as shown in Figure 4, the cycle begins with nebulization of hydrogen peroxide at 27-35% in microdroplets within a nebulization chamber 6 using a piezoceramic ultrasonic transducer that vibrates at 2.4 MHz. The transducer can operate continuously or in accordance with a suitable duty cycle so that the nebulization is intermittent. The spray of the nebulizer has microdroplets which have the same composition as the volumetric solution from which they were derived. Once produced, the dew of the nebulizer is transported through a driving fan 8 to the membrane concentrator system 4 where it is concentrated by means of evaporation in submicron sized particles or nano-nebulizer. The membrane concentrator 4 is preferably a multi-layer device where the nebulizer flows on membrane layers which have an alternating air flow on the other side. The selective removal of a proportion of water vapor from the nebulizer occurs in the membrane concentrator due to the differential partial pressures of water and hydrogen peroxide. The concentrator can be electrically heated if it is required to provide the desired effect. Not only do the drops become more concentrated (-60 - 70%), due to the loss of solvent (water) they become smaller. The smaller droplets also increase the surface area / volume and thus become more stable. The net result is an ultrafine, stable and concentrated or nano-fogging mist. At the point of exit from the concentrator, the spray is "terminally" concentrated, so that no other concentration of hydrogen peroxide occurs in the sterilization chamber. In a simple embodiment, seen in Figure 2, the membrane concentrator is a modular, stackable assembly, consisting of 4 main components - flow layer, end plate, connecting rod and membrane sheet. Figure 5 shows a preferred stack of concentrator modules. The flow layers 10 and 11 are defined by thin, square or rectangular plates 12 with a large open area in the interior and four grooves (galleries) running parallel to the outer edges, two of which are connected to the interior space through of slots. The orientation of the flow layers (when using square sections), determines the number of layers that are common for any particular gallery, therefore, two different flow lines can operate in a single assembly through the assembly method. The end plates 13 allow the connection of pipe or external devices to the membrane assembly and each end plate has two connection points which correspond to two gallery slots. The slots in these end plates form a manifold, which directs flow up a particular gallery by connection and the connections are offset 90 ° from one another to ensure that they access different galleries. For example, when five layers of flow are stacked one on top of the other in alternate orientations, ie, 90 ° to each other, and separated by sheets of membrane material, they form two groups of flow layers, one having two layers of flow 15 and the other having three separate flow layers 16 within the block. These flow layers are assigned to either the nano-nebulizer (15 in the present case) or cross-flow / counter-flow connections (16 in the present case) and through the regulation of their flow rates, controlled diffusion is possible. The connecting bars are used to compress the layers between the end plates and create a vapor seal, although any design that allows the blocks to fit together in a suitable sealed arrangement can be used. The membrane material 9 also acts as a packing between the layers. Although the vapor pressure of the hydrogen peroxide at room temperature is negligible, and preferably the water evaporates in the membrane concentrator, as a precaution against any flow of hydrogen peroxide leaving the system, the counterflow is carried directly to the destroyer module catalytic where it is treated safely. The semi-permeable membrane 9 in the present example is preferably made of KIMGUARD ™, a three-layer lint-free laminated fabric using polypropylene and having an inner layer which is hydrophobic and resistant to bacterial penetration. The two outer layers provide resistance to abrasion and strength. As a multilayer fabric, it does not have a real pore size, but the fabric is permeable by virtue of microscopic channels that provide a tortuous path that limits the passage of particles to those less than 0.2 microns, that is, it is impermeable to microorganisms less than 0.2 microns. This fabric allows the vapors of hydrogen peroxide and water to penetrate through the channels of the fabric. The channels do not allow the passage of bacteria into the chamber and do not allow the nebulizer to leave. Kimguard has a hydrostatic repellency of 3.8 kPa (hydrophobicity measure) and a transverse dimensional tensile load of 70 Newtons and a machine directional tensile load of 130 Newtons.

The semi-permeable membrane 9 can be any other suitable semi-permeable membrane which facilitates the removal of water and which at the same time is impermeable to microorganisms and nebulising particles. Other fabrics and membranes which are permeable to water vapor and hydrogen peroxide vapors and impenetrable to bacteria can be used, for example TYVEK ™ and SPUNGUARD ™ (However, it has been found that KIMGUARD ™ is 2-3 times more permeable to hydrogen peroxide vapor than TYVEK ™ under the conditions in which it is used herein As will be discussed below, other semi-permeable membrane materials such as NAFION ™ (which is hydrophilic) and the like may also be employed. ™ is a copolymer of tetrafluoroethylene and perfluoro acid 3,6, dioxa-4-methyl-octen-sulfonic acid, these materials are hydrophilic and have a very high hydration water, NAFION ™ is capable of absorbing 22% by weight of water. this variation, the absorption proceeds as a first-order kinetic reaction.The water molecules pass through the membrane and then evaporate into the surrounding air until equilibrium is reached with the humed external ad in a continuous procedure called pervaporation. An external current flow of air on the outer side of the membrane provides a rapid removal of moisture from the outer surface and accelerates the pervaporation process. Unlike a simple penetration, where the molecules simply diffuse through the open pores, in the pervaporation, the membrane is active to selectively remove molecules from one side of the membrane to the other, and can do this to Differential speeds for different types of chemical molecule. In the embodiments described above, the sterilizing agent is a hydrogen peroxide solution as a 35% by weight solution in water which acted as the solvent. Water is the preferred solvent for use with peroxide. The water boils at 100 ° C while the hydrogen peroxide boils at more than 151 ° C at atmospheric pressure. Hydrogen peroxide boils at 151.4 ° C to 760 mm. Figure 1 taken from US 4,797,255 shows (curve A) how the boiling point changes at atmospheric pressure of a water / peroxide mixture with concentration and (curve B) how the gas composition changes. As shown, pure water boils at 100 ° C at atmospheric pressure. It is evident from Figure 1 that the concentration of hydrogen peroxide in the vapor at less than 100 ° C is negligible at atmospheric pressure. The solvent, for example, may be an aqueous or non-aqueous alcohol selected in combination with the sterilizing agent that will be used. The addition to the water of ethyl alcohol results in an azeotropic mixture which reduces the boiling point of the solvent and this allows the water to boil vigorously at lower temperatures than would otherwise be possible. The addition of other azeotropic agents would be equally beneficial. The use of azeotropes to facilitate the removal of solvent from the nebulizer solution particles is within the scope of the invention. It is contemplated that for some biocides, non-aqueous solvents or a combination of suitable solvents may be employed. In the case of hydrogen peroxide, as the water boils vigorously, the concentration of the sterilizing agent increases. If a 35% peroxide solution is used in the invention, the micronebulizer after the steps of heating and removing water vapor will have a concentration, for example, of 60 to 80%. This has the advantage that the starting material can be handled in a relatively safe manner, that the concentration occurs during the process and that subsequently there is no additional need to handle the peroxide. In addition, the average particle size is greatly reduced, the micropubbing particles in the preferred embodiments have an average diameter of less than 1 miera., preferably less than 0.1 microns. The small particle size results in a very stable suspension with negligible sedimentation, provides a significant increase in the liquid / gas interface area, and very high concentrations of liquid sterilant per liter of nebulizer. The inventors believe that there may be a higher concentration of peroxide molecules at the gas / liquid interface in these nanoparticles than what occurs in microparticles. Solutions of a concentration lower or higher than 35% can be used as a starting material and excellent results are obtained with solutions of hydrogen peroxide of 1% or 3% as well as with solutions of 40%, but the time to reach a result Satisfactory with equalized or occluded surfaces was less than optimal with peroxide concentrations below 30%, and handling issues result in a preference for concentrations below 35%. Although the preferred embodiments described have employed aqueous solutions of hydrogen peroxide as the sterilizing agent, solutions of other peroxides and peroxy compounds as well as solutions of peroxy complexes (including complexes not soluble in water in organic solvents) can be employed. Sterilization agents other than peroxides can also be used in the invention, including without limit halo compounds, phenolic compounds, halogenophenolic compounds and other known biocides, with a suitable selection of solvent. Although peroxide concentrations in droplets produced from 30-35% peroxide solution typically reach 60% or more, it is not always necessary to achieve such a high concentration of peroxide. For example, in other preferred embodiments, a starting solution which has a concentration of 10 to 15% peroxide is nebulized and concentrated to about 45 to 60% peroxide. Any starting peroxide concentration can be used, and concentrated at a level up to the theoretical maximum that can be reached under the prevailing relative humidity and temperature conditions. Generally, in practical terms, a peroxide concentration of 10-15% at 30-35% is employed as the starting solution, which is concentrated up to 45-60% or more in the nebulizer.

In an example in which the item to be disinfected is part of an ultrasonic probe 20, for example, a probe of a type that can be inserted into a body cavity for diagnostic purposes, the part of the probe 20 that will be treated is encloses in a chamber 2 (as exemplified in Figure 9). In this case, the camera is a specially configured camera designed so that the entire article does not need to be in the camera, enclosing only that part of the probe that will be treated. The probe can be suspended inside the chamber by means of a seal around the gland where the power cable enters the probe. The nano-nebulizer is then transported to chamber 2 where it is applied to a target surface. The ultrasound device can be inserted into the camera through any of the panels in the device. A possible entry is from the top through a screw cap in which the cable of the device is held and held in place with the insertion in the chamber. The passage of the nano-nebulizer from the concentrator to the chamber is regulated by a check valve 5. The check valves 5 and 12 can control whether the device operates in the form of batches, continuously or through some combination thereof. If the device operates in the form of batches, the valve 5 opens at the appropriate time after the concentration has occurred.

If the device operates continuously, the valve remains open, with the flow rates and residence times of the nebulizer calibrated in advance to be at a maximum when leaving the chamber. Typically, the chamber 2 is constructed with a thermally conductive metal such as stainless steel or aluminum. Various coatings can be applied inside the chamber such as Teflon to reduce the risk of decomposition of the peroxide. The disinfection chamber is electrically heated using heater tracking cable applied to the conductive metal surface. Alternatively, or additionally, hot air can be blown into the chamber. The atmosphere of the chamber for supplying the fan is made up of another chamber connection which is placed on the opposite side of the chamber towards the inlet. The chamber itself is isolated from the generation and recirculation circuit by means of valves which are coupled once the nano-nebulizer cycle is completed (approximately 1-1.5 minutes). This isolation of the adjacent circuit is called "suspended time" or more commonly, "hold" time. The surface of the object 1 to be treated with the nebulizer is exposed to the nano-fogging particles for a sufficient time to sterilize the surface. Surprisingly, it has been found that the resulting nano-nebulizer is not only more rapidly effective than the aerosols of the prior art, but is also highly effective in penetrating matched surfaces, and treating occluded surfaces which are not directly exposed. Although the reason for this is not clear, it may be that a very high density of nano-foggers (eg, 2.0 mg / l or greater than 40% relative humidity) is distributed throughout the volume of the sterilization chamber while that at the same time there is little or no real condensation on the surface. The nano-fogging particles have a much larger surface area in the gas / liquid interface than the original micro-fogging particles and are significantly smaller in diameter, and consequently remain suspended for longer periods. Without intending to be limited to theory, applicants herebelieve that nanoparticles collide on the surface at a frequency greater than the microparticles of the prior art, and have a longer residence time on the surface than vapor molecules . Compared to the prior art aerosol procedures, the surfaces treated by the invention can be dried quickly and relatively not contaminated with residual peroxide. When treating a lumen, it is preferred that the lumen be connected to receive a flow of the nebulizer through the lumen. In an advisable manner, external and even surfaces are also exposed to the nebulizer in the chamber or cassette. The chamber 2 can be formed entirely of a semi-permeable membrane or fabric or can have a wall of which at least a part is a semi-permeable membrane or fabric and can have any suitable shape or design considering the requirements of the process described herein and can be sealed in any way impenetrable to microorganisms. Other membranes or semi-permeable fabrics may be selected based on the teaching provided herein. The container can be permanently connected to the nebulizer circuit or it can be able to be connected and disconnected through a tube and spigot connection, through suitable connectors or other means. Once the suspended time is completed (approximately 1 - 2 minutes), the system moves to the catalytic destruction mode or simply "empty". It is in this cycle that a suction fan is connected which controls (opens under pressure) a check valve that is connected to the chamber while another valve allows fresh air to enter the chamber at a controlled rate. This cycle moves the nano-nebulizer to the catalytic destroyer module where a catalyst is used to convert the hydrogen peroxide into oxygen and harmless water vapor. The catalytic destroyer module is composed of ceramic honeycomb layers cooked with metal oxide that interspersed equally treated ceramic beds packaged in a suitable container. The amount of catalyst is proportional to the amount of peroxide extracted from the chamber as well as the flow velocity of the chamber. The termination of this cycle takes approximately 1 minute and after completion, the camera can be accessed to recover the disinfected target device. In this configuration, the total cycle time for high level disinfection approaches 5 minutes or less. It is understood that the time to reach sterilization is more onerous and can take significantly longer. In some preferred embodiments, the density of droplets in the aerosol that passes from the pre-concentrator to the sterilization chamber can be measured by passing an infrared beam through the connecting conduit to a detector and measuring the attenuation of the beam. This varies with the droplet density of the aerosol and gives a measure of the amount of peroxide liquid / unit of time entering the sterilization chamber. The infrared is preferably of a frequency which is not absorbed by peroxide per se and therefore does not register peroxide vapor, if any. A knowledge of aerosol density, temperature and residence time allows certification of the result if desired. The preconcentrator can be operated in such a way that it always emits nebulizer comprising peroxide at a predetermined theoretical maximum concentration, thus avoiding the need to determine the peroxide concentration at any point of the sterilization process.

EXAMPLES Figures 8A and 8B show the resulting concentration of peroxide after use of the membrane concentrator of the present invention. Figures 8A and 8B compare the percentage of relative humidity (RH) and peroxide (H2O2) levels (ppm) measured within a 3 liter chamber with an aerosol flow rate at 9 I / minute in the membrane concentrator before described, or bypassing it completely. The starting peroxide concentration was 30%. The membrane used in this case was KIMGUARD, although similar profiles are obtained with NAFION and TYVEK. By deviating the membrane / modulus concentration (FIG. 8A) 46% relative humidity and a peroxide level of about 980 ppm are revealed. However, when using the membrane concentrator, it can be seen (Figure 8B) that the corresponding concentration of peroxide is more than 2100, and that the relative humidity decreased to 28%. Indeed, the use of the preconcentrator of the present invention has eliminated a large amount of water, leading to more than twice the peroxide concentration. Tables 1, 2 and 3 below indicate that the increase in backflow results in an increase in peroxide concentration in the 3 liter chamber over a period of 5 minutes with NAFION showing the greatest effect.

TABLE 1 Influence of backflow velocity in membrane modulus of NAFION in the ratio between hydrogen peroxide and water by weight in the disinfection chamber at 50 ° C TABLE 2 Influence of backflow velocity in membrane module of TYVEK in the ratio of hydrogen peroxide to water by weight in the disinfection chamber at 50 ° C TABLE 3 Influence of backflow velocity in membrane modulus of KIMGUARD in the ratio between hydrogen peroxide and water by weight in the disinfection chamber at 50 ° C Table 4 below indicates the effect of the nano-nebulizer procedure using the membrane concentrator on carriers inoculated with 5x106 cfu β. stearothermophilus / carrier with 400 ppm hard water and 5% horse serum. The flow velocity of the aerosol was 9 I / min, the counterflow was 9 I / min, the temperature in the chamber was 50 ° C and the starting concentration of the peroxide was 30%. The peroxide supplied was 0.11 g / l.

TABLE 4 Time relationship for spore reduction in different surface conditions The following is illustrative of the types of particle sizes that can be obtained through the preconcentrators of the present invention. Table 5 shows the particle size distribution of a nebulizer from an ultrasonic nebulizer fed with 30% hydrogen peroxide solution at various temperatures. This would represent the input particle sizes for the preconcentrators of the present invention.

TABLE 5 Table 6 shows the particle size data at 25 ° C of the nebulizer when a NAFION membrane was used with various air flow velocities on the outer side.

TABLE 6 Table 7 shows the particle size data at 25 ° C of the nebulizer when a KIMGUARD membrane was used with various air flow velocities on the outer side.

TABLE 7 It can be seen that the particle size has decreased by approximately half in the case of Nafion (which corresponds to a drop volume reduction of approximately 30% of the original size) and approximately one third in the case of Kimguard (corresponding to a drop volume reduction of approximately 13% of the original size). 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 biocide can be used including unlimited halogenated biocides, phenolic biocides and biocides of quaternary compounds and it may be convenient to use solvents other than water. In a similar way, although the invention has been exemplified herein primarily with respect to starting solutions having 35% peroxide, other starting concentrations may be employed, although concentrations between about 20% and 35% are preferred. The principles presented in this document can be applied to concentrate the peroxide in such vapor processes by penetration or pervaporation through a membrane, without the need for pressure reduction. However, the benefits (described in the co-pending application) of using the aerosol of the invention would be lost as a sterilant would be lost.

Claims (35)

NOVELTY OF THE INVENTION CLAIMS

1. - An apparatus for concentrating a nebulizer comprising: a nebulizer flow conduit; a counterflow conduit; and wherein at least a portion of said nebulizer flow conduit and said counterflow conduit define respective opposite sides of a gas permeable membrane.

2. The apparatus according to claim 1, further characterized in that it additionally comprises a nebulizer in communication with the nebulizer flow conduit.

3. The apparatus according to claim 1 or 2, further characterized in that it additionally comprises humidity control means for controlling the humidity of a backflow entering the backflow duct.

4. The apparatus according to any of claims 1-3, further characterized in that it comprises: a plurality of alternating nebulizer flow conduits and corresponding counterflow conduits; and wherein at least a portion of each said nebulizer flow conduit and an adjacent counterflow conduit define respective opposite sides of a gas permeable membrane.

5. - The apparatus according to any of claims 1-4, further characterized in that the alternating nebulizer flow conduits and counterflow conduits are in a layer configuration.

6. The apparatus according to any of claims 1-4, further characterized in that the alternating nebulizer flow conduits are in a coaxial, concentric tubular arrangement.

7. The apparatus according to any of claims 1-3, further characterized in that it is for concentrating a nebulizer, comprising: a nebulizer flow conduit; at least two backflow ducts; and wherein at least a portion of said nebulizer flow conduit and said counterflow conduits define respective opposite sides of gas permeable membranes.

8. The apparatus according to any of claims 1-3, further characterized in that it is for concentrating a nebulizer, comprising: at least two nebulizer flow conduits; a counterflow conduit; and wherein at least a portion of said counterflow conduit and said nebulizer flow conduits define respective opposite sides of gas permeable membranes.

9. The apparatus according to any of the preceding claims, further characterized in that each nebulizer flow conduit comprises an inlet and an outlet, each counterflow conduit comprises an inlet and an outlet, and the nebulizer flow and the backflow are in equal or opposite directions.

10. The apparatus according to any of claims 1 to 7, further characterized in that each nebulizer flow conduit comprises an inlet and an outlet, and the counterflow conduit directs a counterflow in a direction at an angle towards the direction of Nebulizer flow.

11. A method for concentrating a solution consisting of an active in a solvent and having a first active: solvent ratio comprising the steps of: (1) nebulizing the solution to form a nebulizer having drops wherein the concentration of active is in about said first ratio, (2) providing a flow of the nebulizer to a first side of a gas permeable membrane; and (3) providing a counterflow of a gas to a second side of the gas permeable membrane to increase said first ratio of active: solvent on the first side to a second active: solvent ratio greater than the first active: solvent ratio .

12. A method for concentrating a nebulizer comprising the steps of: (1) providing a flow of a nebulizer consisting of an active in a solvent and having a first active: solvent ratio to a first side of a permeable membrane to gas; and (2) providing a counterflow of a gas to a second side of the gas permeable membrane to increase said first ratio of active: solvent on the first side to a second active: solvent ratio greater than the first active: solvent ratio .

13. The method according to claim 11 or 12, further characterized in that the active is a biocide and the concentrated nebulizer is used to disinfect and / or sterilize an article.

14. The method according to any of claims 11-13, further characterized in that the solvent is water.

15. The method according to any of claims 11-14, further characterized in that the active is selected from hydrogen peroxide or a peroxy compound.

16. The method according to any of claims 11-15, further characterized in that the first ratio of active to solvent is less than 35% by weight.

17. The method according to any of claims 11-16, further characterized in that the second ratio of active: solvent is greater than 60% by weight.

18. The method according to any of claims 11-17, further characterized in that the backflow of gas is provided at a rate and for a time such that the second ratio reaches an equilibrium ratio above which it will no longer increase .

19. The method according to any of claims 11 - 18, further characterized in that the gas is air or air conditioning with moisture.

20. - The method according to any of claims 11-19, further characterized in that the semi-permeable fabric or membrane is a woven, or non-woven fabric, or a sheet or film or a combination thereof and a construction of a single layer or multiple layers.

21. The method according to any of claims 11-20, further characterized in that the semipermeable membrane is hydrophobic.

22. The method according to any of claims 11-21, further characterized in that the semipermeable membrane is selected to ensure that the nebulizer particles in the first active: solvent ratio are initially unable to penetrate through it.

23. The method according to any of claims 11-22, further characterized in that the membrane is suitable for pervaporation.

24. The method according to any of claims 11-23, further characterized in that the nebulizer is an aqueous peroxide solution having an initial concentration of 6% -35% by weight of peroxide.

25. The method according to any of claims 11-24, further characterized in that the solution is nebulized in an ultrasonic nebulizer operated at more than 2.0 MHz and which generates an aerosol in which the particles have a scale distribution about 1 - 10 microns in size are suspended in a stream of air.

26. The method according to any of claims 11-25, further characterized in that the semipermeable membrane is selected to remove one or more vapors through a pervaporation process.

27. A method for disinfecting or sterilizing an article, comprising contacting a suitable biocidal solution concentrated through a method of any of claims 9-24 with the article as a nebulizer or vapor.

28.- A method to disinfect or sterilize an article, comprising the steps of: (1) vaporizing a solution consisting of an active in a solvent and having a first active: solvent ratio, (2) providing a steam flow to a first side of a gas permeable membrane; and (3) providing a gas backflow to a second side of the gas permeable membrane to increase said first ratio of active: solvent on the first side to a second active: solvent ratio greater than the first active: solvent ratio, and (4) allowing, or causing the vapor from step 2 to contact the article for a sufficient time to disinfect or sterilize it.

29. The method according to claim 28, further characterized in that it is carried out at atmospheric or higher pressure.

30. The method according to any of claims 27 or 28, further characterized in that the backflow of gas is provided at a rate and for a time such that the second ratio reaches an equilibrium ratio above which it will no longer increase.

31.- 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 inside a first container having a wall of which at least one part is a semi-permeable fabric or membrane; (2) the semi-permeable fabric or membrane is selected to allow steam to pass from the inside to the outside of the container and at the same time provide a barrier against the entry of microorganisms and against the exit of nebulizer particles; (3) admitting a biocidal solution comprising a biocide dissolved in a solvent in a second container; (4) concentrating the biocide in the second container by removing the solvent, to form a concentrated biocide, (5) introducing the concentrated biocide as a liquid or a vapor or a combination thereof from the second container to the first; and wherein steps (4) - (5) are performed at atmospheric or higher pressure.

32. The method according to claim 31, further characterized in that the concentration step is in accordance with any of claims 11 - 26.

33.- The method according to claim 31, further characterized in that the membrane of the first container is impenetrable to microorganisms and the article is sterilized and stored sterile in the first container.

34.- The method according to any of claims 11-33, further characterized in that the nebulizer in the first ratio has 90% of particles in the 3 - 5 μm scale.

35. The method according to any of claims 11-34, further characterized in that the nebulizer in the second ratio has an average particle diameter of less than 1.0 microns.