WO2025038984A1

WO2025038984A1 - Portable on-demand sterilization

Info

Publication number: WO2025038984A1
Application number: PCT/US2024/042826
Authority: WO
Inventors: Sumner Barenberg; Robert Cameron; Xiao Tian
Original assignee: Phiex Technologies, Inc.
Priority date: 2023-08-16
Filing date: 2024-08-16
Publication date: 2025-02-20

Abstract

Gas generating and releasing devices, which produce and release chlorine dioxide gas without detectable amounts of any toxic by-products such as chlorine gas, chlorites, or chlorates are provided herein. Such devices are useful for disinfection, sanitation, sterilization, and control of biological or pathogenic contamination.

Description

PORTABLE ON-DEMAND STERILIZATION

FIELD OF THE INVENTION

[0001] A gas generating and releasing device comprising a container with walls and a closure to seal the container, wherein the container is configured to house chlorine dioxide generating components is provided herein. The chlorine dioxide generating and releasing devices are useful in various applications such as disinfection, sanitation, sterilization, and control of biological or pathogenic contamination.

BACKGROUND OF THE INVENTION

[0002] Currently, ethylene oxide is used in the sterilization of medical devices and other products. Ethylene oxide is recognized by the U.S. Food and Drug Administration to have potential adverse impacts on the environment and on public health. The FDA is encouraging changes to ethylene oxide sterilization processes and facilities that will reduce the amount of ethylene oxide on medical devices.

[0003] Chlorine dioxide is a strong oxidizing agent, antiseptic, and bactericide that is used as a disinfectant, bleach and sterilizing agent. Detectable amounts of toxic by-products including chlorine gas, chlorates and/or chlorites have been observed when chlorine dioxide is generated from some conventional chlorine dioxide-generating products.

SUMMARY OF THE INVENTION

[0004] A gas generating and releasing device is provided, which comprises: a container comprising walls, a closure to seal the container, an optional means for releasing gas from at least a portion of the container, and an optional separator defining at least two chambers within the container; and a gas generating combination. The gas generating combination comprises a chlorine dioxide precursor; an oxidizing agent or an acid; an optional quenching compound; an optional diluent; an optional desiccant or dehumidifying agent; and an optional indicator configured to change color when exposed to chlorine dioxide gas to indicate whether gas has been generated. The container is configured to house the gas generating combination within the container. [0005] A gas generating and releasing device is also provided, which comprises: a substrate comprising a front surface, a back surface and a side surface; and a gas generating film. The gas generating film comprises a chlorine dioxide precursor; an oxidizing agent or an acid; an optional quenching compound; an optional diluent; an optional desiccant or dehumidifying agent; and an optional indicator configured to change color when exposed to chlorine dioxide gas to indicate whether gas has been generated. The gas generating film is between the front and back surfaces of the substrate or is on an exterior surface of the front surface, the back surface or the side surface of the substrate.

[0006] Other objects and features will be in part apparent and in part pointed out hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

[0007] Figure 1 is a photograph of dehumidifying polishing media showing hydrophilic media/matrix (shown in white and gray) and desiccant/polishing media particles (shown in black).

[0008] Figure 2 depicts chlorine dioxide gas flow across a hydrophilic media/matrix.

[0009] Figure 3 shows chlorine dioxide concentration as a function of time for 15 Type I device prototypes.

[0010] Figure 4 is a graph depicting the measured CIO2 concentration (shown as a diamond) at approximately 20 minutes for each of the samples as a function of the mass of NaCIO2 present. The theoretical concentration values (shown as a square) expected for the same amount of NaCICh based on the reaction shown in Equation 2 are plotted along with the actual data.

[0011] Figure 5 shows the CIO2 concentration generated as a function of time by various designs which utilized the oxidation of chlorite by persulfate to generate CIO2.

[0012] Figure 6 show titration data for two of the designs shown in FIG. 5 continued out to 24 hours.

[0013] Figure 7 shows CIO2 concentration generated as a function of time for the Sm-ll prototype. [0014] Figure 8 shows CIO2 concentration generated as a function of time for Type III devices containing two different chlorite solution concentrations, 5 and 30%.

[0015] Figure 9 shows CIO2 concentration generated as a function of time for the alternate co-reactants.

[0016] Figure 10 shows CIO2 concentration generated as a function of time for CIO2 scavenger devices.

[0017] Figure 11 depicts a chlorine dioxide generating cartridge device that feeds chlorine dioxide into a rotating porous drum having a closure through which objects to be sterilized are placed. The objects are sterilized by the chlorine dioxide/air fed into the rotating drum, and the air leaving the drum through an outlet is purified with an activated charcoal filter and recycled.

[0018] Figure 12 shows two portable gas generating devices wherein gas generation is activated by twisting a portion of the device to initiate a reaction between the chlorine dioxide precursor and the oxidizing agent or acid.

[0019] Figure 13 shows hang tag devices activated by manually pushing on the circle on the tag.

[0020] Figure 14 depicts a portable decontamination device activated by manually pushing on the circle on the device to rupture a frangible and initiate a reaction between the chlorine dioxide precursor and the oxidizing agent or acid. The gas is released through a gas-permeable, liquid-impermeable covering such as a TYVEK film which seals the openings in the device.

[0021] Figure 15 shows a portable multilayer gas generating device activated by peeling the layer away from a backing or by pressing the layer.

[0022] Figure 16 depicts a portable gas generating device which may include interior frangible dividers activated by pressing the circle on the device to fracture the stress-sensitive frangible.

[0023] Figure 17 depicts microencapsulated precursor ingredients including liquid constituents.

[0024] Figure 18 shows a break seal puck device containing a chlorine dioxide precursor powder, a glass ampule or frangible containing an oxidizing agent or an acid, and an additional glass ampule or frangible containing a diluent, and a break seal pressure point for breaking or fracturing the ampules or frangibles to activate the precursor to generate chlorine dioxide.

[0025] Figure 19 shows a break seal puck device containing a chlorine dioxide precursor powder, a glass ampule or frangible containing an oxidizing agent or an acid, and an additional glass ampule or frangible containing a diluent, and a break seal pressure point for breaking or fracturing the ampules or frangibles to activate the precursor to generate chlorine dioxide.

[0026] Figure 20 depicts a graphic representation of a device comprising a container, a closure to seal the container, a separator defining two chambers within the container, a precursor frangible sachet in a chamber, and a frangible sachet containing a quenching compound in the other chamber.

[0027] Figure 21 shows a portable on demand sterilizer pouch including a multilayer film including a chlorine dioxide precursor at the top of the pouch, a chlorine dioxide gas indicator within an upper chamber of the pouch, a separator between the upper and lower chambers of the pouch, and a quenching agent in the lower chamber of the pouch. An object to be sterilized can be placed in the upper chamber of the pouch by opening the closure, placing the object, and closing the closure (e.g., with a locking mechanism such as a zip lock). Before activation, the indicator can be red to indicate that the object has not been sterilized. During sterilization, the indicator can turn yellow. After sterilization is completed, the indicator can turn green to indicate that the object is sterilized. The multilayer strip is activated manually (e.g., by pulling off a cover strip in contact with the multilayer strip or by pressing the multilayer strip). After the object is sterilized in the upper chamber, the lower chamber is activated so that the chlorine dioxide gas will pass through the separator into the lower chamber and be quenched or absorbed by the quenching agent.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] The present invention relates to gas generating and releasing devices, which generate and release chlorine dioxide gas with an improved safety profile. More specifically, these devices generate and release chlorine dioxide gas without detectable amounts of any toxic by-products such as chlorine gas, chlorates and/or chlorites. [0029] As a first aspect of the invention, a gas generating and releasing device is provided, which comprises: a container comprising walls, a closure to seal the container, an optional means for releasing gas from at least a portion of the container, and an optional separator defining at least two chambers within the container; and a gas generating combination. The gas generating combination comprises a chlorine dioxide precursor; an oxidizing agent or an acid; an optional quenching compound; an optional diluent; an optional desiccant or dehumidifying agent; and an optional indicator configured to change color when exposed to chlorine dioxide gas to indicate whether gas has been generated. The container is configured to house the gas generating combination within the container.

[0030] Chlorine dioxide gas generating devices can be made to provide a wide range of concentrations and delivery periods by separately packaging two or more reactive components to be mixed upon demand by the user by an activation mechanism. The two components are a chlorine dioxide precursor, and an oxidizing agent or an acid. The components can be liquid, solid or a combination of liquid and solid. Various chemistries may be used to generate a wide range of concentrations of the desired gas or combination of gases. The concentration of the reactants can be adjusted to achieve the various gas concentrations.

[0031] Various chemistries can be used to produce a variety of gases. Chlorine dioxide is easily produced either by the acidification (Equation 1 ) or oxidation (Equation 2) of sodium chlorite (NaCIO?). Equation 1

Equation 2

[0032] A container for gas generating and releasing includes but is not limited to a pouch or bag, a sachet, a tube or stick such as a light stick, a plastic housing, a bellows, a channel, a cartridge, a drum, or a puck.

[0033] The container or the walls of the container can be made of any of the materials standardly used in the art including but not limited to polyethylene, polypropylene, polyvinyl chloride, polytetrafluoroethylene such as TEFLON, nonwoven high density polyethylene fiber, such as TYVEK or any combination thereof. [0034] In one aspect, the container is liquid impermeable and gas permeable. Such a container would retain liquid components within the container while allowing release of the generated gas through the container.

[0035] In another aspect, at least a portion of the container is air permeable for gas release.

[0036] When the container includes means for releasing gas from at least a portion of the container, the means for releasing gas can be one or more openings extending through a wall of the container. For example, the container can have pores or openings extending from an interior wall to an exterior wall, which are configured for release of chlorine dioxide. One of ordinary skill in the art can readily select containers with appropriate pore size and density. For example, the container can be adapted to include a porous filter or membrane in a wall of the container. The generated chlorine dioxide gas can exit the device through the pores of the filter or membrane.

[0037] By way of example and not of limitation, the packaging material and design can be used to control the generation and delivery rate of the generated gases ranging from seconds to days, e.g., by manipulating the gas permeability of the container and/or the size and density of the pores within the container.

[0038] The closure that seals the container can be a locking mechanism such as a zip-lock. Such closures are well known and widely commercially available in the art.

[0039] The separator defining at least two chambers within the container can be a membrane, a mesh, a film or a foam.

[0040] When a separator is present, the separator can be made from glass wool, a hydrogel, polyethylene, polypropylene, polyvinyl chloride, polytetrafluoroethylene such as TEFLON, nonwoven high density polyethylene fiber such as TYVEK, or any combination thereof.

[0041] When the separator is a membrane, the membrane can include the membrane materials listed above and/or a foaming agent. The foaming agent can include, but is not limited to, a detergent such as sodium lauryl ether sulfate or ammonium lauryl sulfate, a polyurethane, a polyethylene foam, a hydrophilic fiber, or any combination thereof. [0042]As an example, the container can comprise a separator; the chlorine dioxide precursor in a first chamber of the at least two chambers; and the quenching compound in a second chamber of the at least two chambers. The device is configured such that the separator fractures or breaks upon application of pressure.

[0043] In more general terms, the method of activation can also be varied from simple manual activation by squeezing, breaking, rupturing, disrupting, or crushing a component primary containment, to elaborate remotely actuated mixing, to automated activation in response to external stimuli.

[0044] By way of example and not of limitation, the separator can be a break seal.

[0045] Each chamber can be divided into smaller chambers adapted for items to be placed into each chamber.

[0046] The chamber can be a frangible or can include a frangible, such as an ampule. By way of example, the chlorine dioxide precursor can be in the first of the at least two frangibles and the quenching compound can be in the second of the at least two frangibles.

[0047] Frangibles are well known in the art and can be made from materials such as a composite material, glass, onion skin glass, a plastic, a sealant comprising a low- density polyethylene and oriented polypropylene coextrusion, or any combination thereof.

[0048] When the chambers are frangibles such as the ampules, at least one of the chlorine dioxide precursor and the quenching compound, or preferably both the chlorine dioxide precursor and the quenching compound are liquids.

[0049] Barrier materials can be included in the device to alter the rate at which the generated CIO2 is released into the surrounding environment.

[0050] Altering the concentration of the reactants is an effective method of changing the potency of the device without significantly changing the manufacturing process or device appearance. For example, substitution of the co-reactant (oxidizing agent or acid) used to convert the chlorite to CIO2 can alter the gas generation rate over a wide range. [0051] As noted above, the gas generating combination in the container comprises: a chlorine dioxide precursor; an oxidizing agent or an acid; an optional quenching compound; an optional diluent; an optional desiccant or dehumidifying agent; and an optional indicator configured to change color when exposed to chlorine dioxide gas to indicate whether gas has been generated.

[0052] The gas generating combination comprises from about 10 wt. % to about 35 wt. % of a chlorine dioxide precursor, from about 5 wt. % to about 40 wt. % of an oxidizing agent or from about 1 wt. % to about 10 wt. % of an acid, up about 25 wt. % of a diluent, and up to about 60 wt. % of a desiccant or dehumidifying agent. Preferably, the gas generating combination comprises from about 10 wt. % to about 35 wt. % of a chlorine dioxide precursor, from about 5 wt. % to about 40 wt. % of an oxidizing agent or from about 1 wt. % to about 10 wt. % of an acid, from about 15 wt. % to about 25 wt. % of a diluent, and from about 20 wt. % to about 60 wt. % of a desiccant or dehumidifying agent.

[0053] A preferred composition, which is for extended release of chlorine dioxide over more than 24 hours, is as follows:

[0054] Methods of preparing a moisture-activated powder from a chlorine dioxide precursor (e.g., sodium chlorite), a desiccant (e.g., a silicate and an anhydrous material), and an oxidizing agent (e.g., an inorganic acid-releasing agent) have been described in U.S. Patent Publication No. 2024/0041044 entitled “Moisture-Activated Chlorine Dioxide-Releasing Powder and Method of Manufacture,” which is herein incorporated by reference in its entirety. Such a powder can be used in the gas generating combination or can be incorporated into the gas generating film described herein. The powder can be activated by a diluent such as water or by moisture.

[0055] The chlorine dioxide precursor can be in the form of a powder or microcapsules capable of releasing the chlorine dioxide precursor upon contact of the powder or the microcapsules with the diluent.

[0056] Examples of the chlorine dioxide precursor include, but are not limited to, sodium chlorate, sodium chlorite, ammonium chlorite, a chlorite salt of a primary amine, a chlorite salt of a secondary amine, a chlorite salt of a tertiary amine, a quaternary ammonium chlorite, a trialkylammonium chlorite, or any combination thereof. Preferably, the precursor comprises sodium chlorite. The gas generating combination or film contains from about 10 wt. % to about 35 wt. % of the chlorine dioxide precursor.

[0057] Without being bound by any particular theory, it is desirable to maximize bound and interfacial water while concurrently minimizing available free water in the chlorine dioxide precursor, for example, by embedding the chlorine dioxide precursor in a hydrophilic hydrogel matrix.

[0058] The quenching compounds include, but are not limited to, activated charcoal, carbon, humidity chips, compressed hydrophilic foam, compressed hydrophilic fibers, a superabsorbent polymer, a hydrocolloid, a hydrogel, an osmotic material, an absorbent gelling material, a polyacrylic acid, an ethylene maleic anhydride copolymer, crosslinked carboxymethylcellulose, a polyvinyl alcohol copolymer, sodium bicarbonate and an acid, or any combination thereof. The quenching compound is included in a chamber adjacent to a chamber containing the chlorine dioxide precursor to absorb chlorine dioxide gas after sterilization (see, e.g., Figure 27).

[0059] Suitable oxidizing agents include, but are not limited to, an alpha-hydroxy alcohol, an acyl halide, an anhydride, calcium chloride, a carboxylate of polyphosphate, a condensed phosphate, a dialkyl phosphate, a metal salt, a phosphosiloxane, a phosphate ester, a phosphosilicate, a phosphosilicic anhydride, a polyphosphate, sodium hydrogen ascorbate, sodium persulfate, sodium sulfite, sorbitan monostearate, sorbitol monostearate, sulfonic acid chloride, a sulfonic acid ester, a trialkylsilyl phosphate ester, tetraalkyl ammonium polyphosphate, monobasic potassium phosphate, potassium polymetaphosphate, sodium metaphosphate, a borophosphate, an aluminophosphate, a silicophosphate, a sodium polyphosphate, potassium tripolyphosphate, sodium-potassium phosphate, or any combination thereof. The gas generating combination or film can contain from about 5 wt. % to about 40 wt. % of an oxidizing agent.

[0060] Suitable acids include, but are not limited to, boric acid, carboxylic acid, citric acid, hydrochloric acid, malic acid, a mineral acid, phosphoric acid, sulfonic acid, tartaric acid, or any combination thereof. The gas generating combination or film can contain from about 1 wt. % to about 10 wt. % of the acid.

[0061] Within the container, the oxidizing agent or acid is provided within a chamber separated from the chlorine dioxide precursor prior to activation.

[0062] If the diluent is present in the container, it is placed within a chamber separate from the chlorine dioxide precursor prior to activation.

[0063] The diluent can include, but is not limited to, sodium bicarbonate, a carbide, a clay, glass fiber, a metal oxide, a nitride, a silica gel, a silicate, silicon dioxide, water, a zeolite, or any combination thereof. The gas generating combination or film contains up to about 25 wt. % of the diluent, and preferably from about 15 wt. % to about 25 wt. % of the diluent.

[0064] A desiccant or dehumidifying agent can be included to desiccate and polish (purify) the chlorine dioxide gas that is generated. The desiccant or dehumidifying agent decreases ambient humidity in the container while allowing for diffusion of chlorine dioxide gas from the device. The desiccant or dehumidifying agent includes, but is not limited to activated charcoal, alumina, an aluminosilicate, analcime, arginine, bauxite, calcium carbonate, calcium chloride, calcium sulfate, chabazite, charcoal, chondroitin sulfate, a clay, clinoptilolite, crystalline silica, gelatin, heulandite, glycoaminoglycan, magnesium sulfate, moisture-depleted silica gel, a molecular sieve, montmorillonite clay, natrolite, phillipsite, polylactic acid, potassium permanganate, pure silica, quartz, silica sand, a silicate, silicic oxide, silicon oxide, sodium chloride, sodium sulfate, stibite, a sugar, a zeolite, or any combination thereof. The gas generating combination or film contains up to about 60 wt. % of the desiccant or dehumidifying agent, and preferably from about 20 wt. % to about 60 wt. % of the desiccant or dehumidifying agent.

[0065] The desiccant or dehumidifying agent can be included or embedded within a mitigating layer. The mitigating layer can include, but is not limited to, calcium chloride, a cellulose, a clay, cotton, a hydrogel, a hydrophilic clay, a hydrophobic clay, a natural fiber, a nonwoven polymer, a non-powdered polymer, a powdered polymer, sawdust, silica gel, sodium hydrogen ascorbate, sodium sulfite, sponge particles, talcum powder, a woven polymer, a zeolite, or any combination thereof. For example, a desiccant can be embedded as particles or microcapsules in the mitigating layer or in a dry hydrophilic media such as cotton, a polymer film or fiber or a porous polymer film or fiber.

[0066] The indicator can be any compound available in the art that changes color when exposed to chlorine dioxide gas. Suitable indicators include, without limitation, betacarotene, Yellow #5, rifampin, Yellow #8, tetracycline, Red #40, Red #3, Blue #2, Evans blue, Green #3, Blue #1 , methylene blue, indocyanine green, betanin, beet juice, Blue #29, Blue #97 or Blue #104.

[0067] The indicator can be a separate component of the device and not part of the gas generating combination or gas generating film. The indicator, for example, can be an indicator dye strip.

[0068] The indicator can change color as a function of the reaction kinetics (i.e. , to indicate no sterilization, sterilization in process, or completed sterilization). [0069] The indicator, for example, can be placed near openings, pores or the closure within the container. When the device comprises a gas generating film on a substrate, the desiccant or dehumidifying agent can be an external layer on the gas generating film. The substrate can be, for example, a hang tag, label, dryer sheet, or mask.

[0070] The components of the gas generating combination can be spray dried, microencapsulated or embedded into various films that are coextruded into a multilayer film by methods well known in the art.

[0071]The components of the gas generating combination can also be separated by different components of the device (e.g., separators, chambers, frangibles) to initiate activation of various components when desired.

[0072] Figure 1 shows a dehumidifying agent or desiccant as particles within a hydrophilic media or matrix. Figure 2 shows generated chlorine dioxide gas and moisture flowing through a hydrophilic media or matrix and polished chlorine dioxide gas being released from the media or matrix.

[0073] A gas generating and releasing device is also provided which comprises: a substrate comprising a front surface, a back surface and a side surface; and a gas generating film. The gas generating film comprises: a chlorine dioxide precursor; an oxidizing agent or an acid; an optional quenching compound; an optional diluent; an optional desiccant or dehumidifying agent; and an optional indicator configured to change color when exposed to chlorine dioxide gas to indicate whether gas has been generated. The gas generating film is between the front and back surfaces of the substrate or is on an exterior surface of the front surface, the back surface or the side surface of the substrate.

[0074] The substrate includes but is not limited to a hang tag, a foam, or a film. The substrate can have an optional peelable layer, and the device is configured to generate chlorine dioxide when the substrate is bent or pressed and/or when the peelable layer is peeled away from the substrate. The substrate can be made from materials including but not limited to fibers such as cellulose, polymers, plastics, and other well-known materials for hang tags. [0075] The components of the gas generating film, namely a chlorine dioxide precursor, an oxidizing agent or an acid, and optionally a quenching compound, and/or a diluent, and/or a desiccant or a dehumidifying agent, and /or an indicator have been discussed above.

[0076] The device can be, for example, a multilayered film, a light stick, a foam, or a pouch and can be flat, circular, tubular or any other desired shape. The devices of the invention can be configured, for example, as shown in Figures 11-27.

[0077] The chlorine dioxide gas generating and releasing devices can be used to retard, kill, prevent or control microbiological contamination or biochemical decomposition on a surface of a material, within the material or in the atmosphere surrounding the material. Microbiological contaminants can include bacteria, viruses, mold, and fungi.

[0078] As used herein, retarding, preventing, or controlling biological contamination is also referred to as “sanitization,” “disinfection” or “sterilization.” Biological contamination can include bacteria, viruses such as corona viruses (e.g., SARS-COV-2 and variants thereof such as the Delta or Omicron variants), mold and fungi. Chlorine dioxide, for example, is used following biological warfare to deactivate the biological contaminant (e.g., anthrax) or for other military decontamination.

[0079] The chlorine dioxide gas generating and releasing devices can also be effective in disinfecting electronics without corroding the electronics. This can be advantageous in combatting the effects of a pathogen on electronics in battlefield contamination resulting from the use of biowarfare.

[0080] Having described the invention in detail, it will be apparent that modifications and variations are possible without departing from the scope of the invention defined in the appended claims.

EXAMPLES

[0081] The following non-limiting examples are provided to further illustrate the present invention. EXAMPLE 1

[0082] A Type I device was produced by first sealing a break-neck ampoule (A) containing 5g of a 20% NaCIC>2 (technical) solution. The ampoule was then snugly inserted into a short length of flexible PVC tubing (C). The interior cavity (B) was then filled with 5.3g of a mixture of 25% sodium persulfate (Na2S20s, powdered) in silica gel (200-400 mesh, 60A). The tube was capped with a small glass vial, which had been cut in half to remove the bottom. A gas permeable non-woven polymer (TYVEK) sheet (D) was stretched across the mouth of the vial, and a septum lid (without the septum) was screwed onto the vial to hold the sheet in place.

[0083] A Type II device was fabricated by sealing about 0.2ml concentrated hydrochloric acid in a 4”x1/18” o.d. glass tube (A). This sealed ampoule was placed inside a Vi” o.d. PFA TEFLON tube (C) with one end sealed. Approximately 0.4ml of a solution prepared from equal amounts of a 30% NaCIO2 solution and 2.5 ratio sodium silicate solution (14% NaOH) was then transferred to the TEFLON tube to occupy the annular space (B). The open end of the TEFLON tube was then heat sealed to make a completely encapsulated liquid and liquid filled ampoule.

[0084] A Type III device was a refinement of a Type I device to insure more complete delivery of the chlorite solution to the solid co-reactant. Several sets of this device design were fabricated and are specifically identified in the table below. A thin walled (“onion skin”) glass ampoule (A) was first filled with sodium chlorite solution and sealed. A pouch (D) was then formed by heat sealing TYVEK sheets on three sides. A 5m il thick PVC sheet was heat sealed into a cylinder (C) and placed inside the TYVEK pouch as a protective liner against abrasion from the glass ampoule during activation/crushing. The sealed ampoule was placed inside the PVC lined TYVEK pouch, and the surrounding cavity filled with the Na2S2O8/SiO2 mixture (B). Finally, the open end of the pouch was heat sealed to prevent loss of powder. TABLE 1

r00851 Activation and Testing: The Type I device was activated by flexing the PVC tubing to break the sealed ampoule at the pre-scored neck. The liquid contents were then immediately mixed with the solid by inverting and shaking the device. The liquid was absorbed by the silica, resulting in a semi-solid mixture after activation. This design was initially tested for function only (as indicated by the advancing wave of yellow color in the silica bed as the reactants mixed, and the plume of yellow gas exiting the device through the gas permeable membrane), without quantifying the concentration of chlorine dioxide gas that was generated.

[0086] The effectiveness of the Type I device in a cold sterilization application was evaluated by an outside agency using biological indicators (Bl) to confirm sterilization. One of the Type I devices was placed inside a sterilization bag with two humidification sources (Humid chips), a Bl, and two minor packs to be sterilized, each containing three Bls along with various medical devices and materials. The bag assembly was placed inside a sterilization chamber and pre-conditioned for 4 hours at 50 °C. The CIO2 generator was then activated as described above and the sterilization cycle continued for 15.25 hrs. After two purge cycles of 0.5 and 0.25 hrs, the Bis were removed and incubated for 48 hrs.

[0087] The Type II device was activated by bending the Teflon tube, preferably repeatedly to cause several breaks (and thus mixing points) along the length of the thin ampoule and shaking vigorously. This formulation resulted in a rapid precipitation of the silicate upon mixing leaving a solid mass. Concurrently, CIO2 was produced as the mixture becomes acidic, and diffused through the TEFLON outer wall. This device design was again only qualitatively tested for CIO2 release. After activation, the device was placed in a 16-ounce jar containing a filter paper impregnated with potassium iodide. The formation of brown to purple color on the paper was an indication of the presence of CIO2.

[0088]Type III devices were activated by simply crushing the inner ampoule by squeezing the sides of the pouch. Once the ampoule was crushed, the solution and solid immediately reacted causing evolution of the yellow CIO2 gas into the surrounding atmosphere. The liquid was absorbed by the silica and prevented from escaping by the TYVEK. In addition, considerable moisture vapor was produced by the pouch, greatly increasing the local humidity and enhancing the biocidal efficacy of CIO2.

[0089] This Type III device design was first tested by enclosing an activated device in a large (28”x32”) polyethylene bag containing several postal articles. The bag and articles were prepared to allow sampling of the gas inside each of the enclosures (the bag head space, a box, a large 9”x12” envelope, and a standard 4”x9” envelope) by syringe through a septum port without opening the enclosure. The gas inside the articles was sampled.

[0090] The Type III design was further tested by fabricating various sizes (011114-1 to 15), and activating each in a “non-absorbing”, “non-leaking”, known volume (12.8-liter glass flask with a tight-fitting rubber stopper). The resulting CIO2 concentration was determined by iodometric titration over time as described above. A gas tight syringe was used to periodically remove a sample from the flask through a septum covered syringe port.

EXAMPLE 2

[0091]To compare the effect of the outer barrier material in a Type III sealed pouch, several prototypes of this design were prepared using materials with a range of gas barrier properties. Each was constructed by sealing 1 ml of a 30% NaCICte solution (1.2 grams) in an “onion skin” glass ampoule (A). The ampoule was then covered by a woven nylon sheath (commonly used for electrical cable wrap) and placed in a pouch (D). The remaining cavity of the pouch (B) was then filled with 1 gram of a 50% mixture of Na2S20s in silica powder, and the remaining open end sealed. Prototypes were constructed using TYVEK (“standard”), 4 mil thick polyethylene, 8 mil thick SURLYN 1652, and 5 mil thick PVC film.

[0092] Several alternate device designs were fabricated, again using various materials. Type IV was fabricated from a short length of 3/8” i.d. PVC tubing (TYGON) (C). The top of a small sample vial (cut in half, bottom discarded) was forced inside the tubing, and the cap replaced with a septum cap fitted with two layers of TYVEK film secured in the screw threads of the cap (D). An “onion skin” ampoule (A) containing the NaCIO2 solution was then placed inside the tube, and the annular space (B) filled with the 50% persulfate/SiO2 mixture. A second vial top was placed in the remaining end of the tube and capped similarly.

[0093] A Type V device was similar to the previous example but constructed from a short length of polyethylene heat shrink tubing (C). A plug of glass wool (D) was forced into one end of the tube. An ampoule (A) of the chlorite solution with a protective sheath of woven nylon was placed inside the tube, and the annular space (B) filled with the persulfate/SiO2 mixture. A second glass wool plug was then inserted in the open end of the tube, and the entire assembly was gently heated using a heat gun. The heat shrink was heated until the glass wool plugs were firmly held in place.

[0094] A Type VI device was fabricated by first heat-sealing a 5m il thick PVC film into a cylinder with a slight taper (C). A glass wool plug (D) was then inserted into the larger end and pushed through, so it was firmly wedged in the smaller end. An ampoule (A) of the chlorite solution, sheathed in woven nylon was then inserted. The annular space (B) was then filled with the persulfate mixture, and the open end of the cylinder heat-sealed (resulting in a miniature “toothpaste tube” appearance).

[0095] Finally, a Type VII device was based on the simple “light stick” design previously reported as a Type II device. A Type VII device was designed to activate similarly to the Type II device but release the generated gas more quickly. A PFA TEFLON tube (C) was heat sealed at one end to produce a rounded end. A small glass wool plug (D) was then inserted to the closed end of the tube. An ampoule of sodium chlorite solution (A) fabricated from a 5mm o.d. disposable NMR tube was then inserted, and the annular space (B) filled with the persulfate mixture. A second glass wool plug was then inserted into the tube and the end heat-sealed. Small holes were then drilled into the ends of the sealed tube, so the glass wool plugs acted as barriers to prevent loss of the powder mixture through the holes. Two sizes of this design were fabricated.

[0096]Two additional examples of Type II devices were also fabricated for testing. As described previously, a PFA TEFLON tube (C) was heat sealed, and an ampoule (A) of the chlorite solution inserted. The annular space (B) was filled with an aqueous persulfate solution, and the remaining end of the tube was heat sealed.

[0097] The concentration of the reactants can be used to alter the potency of the device without significantly affecting the manufacturing process. Several Type III devices with reduced chlorite solution concentration were fabricated using a TYVEK pouch and persulfate oxidation. A concentration of 5% NaCIC was used for comparison to the 30% samples. The concentration of the persulfate mixture was also reduced but kept in stoichiometric excess (as in all other examples). [0098] Several alternate reactants were tested by fabricating Type III device prototypes with the persulfate mixture replaced by a mixture containing an acid source. In most cases, the acid source was diluted 50% in silica. In the case of the Poultry Guard (Oil-Dri Corp.) and King William clay (Ralston Purina), these materials were used neat. The following table fully describes the design, material of construction, reactants, and concentrations used in the various prototypes.

TABLE 2

r00991 Results: The initial test of the Type I device resulted in immediate, obvious CIO2 gas release as shown in Figure 3. Additional application specific testing of the devices in cold sterilization resulted in sterility (>6 logs kill) in all devices.

[00100] Figure 4 shows the measured CIO2 concentration (shown as a diamond) at approximately 20 minutes for each of the samples as a function of the mass of NaCIO2 present. The theoretical concentration values (shown as a square) expected for the same amount of NaCIC based on the reaction shown in Equation 2 are plotted along with the actual data.

[00101] The CIO2 concentration generated by each of the prototypes is presented in the following figures. The data sets are grouped so that, for example, samples of like composition may be evaluated relative to design, or samples of like design may be evaluated with respect to composition. Several of the TYVEK pouch Type III devices were run to evaluate the reproducibility of the CIO2 concentration, and as a benchmark for all other designs and compositions. Data for the polyethylene and SURLYN pouch Type III devices were not reported due to rupture of the pouch during activation. Gas pressure inside the sealed pouch immediately after activation ruptured the heat-sealed edge, negating any delay or diffusion control of the CIO2 release by the device materials.

[00102] Figure 5 shows the CIO2 concentration generated by the various designs, all of which utilized the oxidation of chlorite by persulfate to generate CIO2. It should be noted that the Lg-VII sample contained twice the reactant charge as the other samples but produced a lower concentration of CIO2. The reduced efficiency of this sample was due to incomplete mixing in the longer device format. With an internal cavity of approximately 6”x0.375”, this aspect ratio was too great to allow even distribution of the reactants along the entire length.

[00103] The same data was plotted in Figure 6 to show titration data for two of the designs continued out 24 hours. The data illustrates the effect of substituting a non- porous outer wall (PVC) for the extremely permeable TYVEK. The initial concentration generated by the PVC-III sample was depressed, with more of the CIO2 remaining trapped in the pouch. The rate at which the concentration decreases in the flask was also retarded when using the PVC-III device. The CIO2 trapped inside the pouch continues to diffuse out into the flask somewhat compensating for the intrinsic loss of CIO2 concentration due to leakage and adsorption.

[00104] Electrochemical sensor data for the Sm-ll sample is shown below in Figure 7. This design provides a substantial delay (5 hours) before CIO2 concentration begins to build inside the test container. The thicker walls of this design resulted in a considerable diffusion barrier for the CIO2 gas, which caused a more controlled increase in concentration, similar to a permeation tube.

[00105] Data collected for the Type III devices containing two different chlorite solution concentrations, 5% and 30%, is shown in Figure 8. For each of the solution concentrations, the resulting CIO2 concentrations were reproducible.

[00106] Figure 9 shows data for the alternate co-reactants trailed for the generation of CIO2. Only the Poultry Guard sample generated CIO2 as quickly or efficiently as the persulfate oxidation (TYVEK-III). This reaction, however, was more exothermic and could potentially result in undesirable decomposition of the CIO2 product.

[00107] Figure 10 shows data collected while evaluating the CIO2 scavenger devices. In each experiment, the TYVEK-III device was activated and allowed to stand for 30 minutes prior to activating the scavenger.

[00108] Conclusions: Three different designs of device gas generators have been fabricated and proven functional. High levels of CIO2 gas were easily generated instantaneously using these devices. Various gases can be generated using a variety of chemistries, either independently, or in combinations. A wide range of concentrations are possible by varying the amount of reactive components.

[00109] CIO2 concentration was shown to be proportional to the amount of NaCIO2 present, provided the co-reactant was present in excess. The actual amount of CIO2 generated approaches the theoretical amount when sodium persulfate was used to oxidize sodium chlorite, and a porous membrane was used for the device packaging to allow evolution of the gas as it was produced. The immediate generation of CIO2 concentrations capable of cold sterilization and biological decontamination has been demonstrated. [00110] Several designs for manually activated gas generators have been demonstrated. The Type VII “light stick” design was inefficient due to a high aspect ratio resulting in poor mixing of the liquid and solid reagents. The Type II “light stick” device worked quite well due to the presence of the common solvent, water, for the two reactants.

[00111] When introducing elements of the present invention or the preferred embodiments(s) thereof, the articles "a", "an", "the" and "said" are intended to mean that there are one or more of the elements. The terms "comprising", "including" and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements.

[00112] In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.

[00113] As various changes could be made in the above products and methods without departing from the scope of the invention, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

Claims

WHAT IS CLAIMED IS:

1 . A gas generating and releasing device comprising: a container comprising walls, a closure to seal the container, an optional means for releasing gas from at least a portion of the container, and an optional separator defining at least two chambers within the container; and a gas generating combination comprising: a chlorine dioxide precursor; an oxidizing agent or an acid; an optional diluent; and an optional desiccant or dehumidifying agent; an optional quenching compound; and an optional indicator configured to change color when exposed to chlorine dioxide gas to indicate whether gas has been generated, wherein the container is configured to house the gas generating combination within the container.

2. The device of claim 1 wherein the container comprises a pouch or bag, a sachet, a tube or stick, a light stick, a plastic housing, a bellows, a channel, a cartridge, a drum, or a puck.

3. The device of claim 2 wherein the pouch comprises polyethylene, polypropylene, polyvinyl chloride, polytetrafluoroethylene, nonwoven high density polyethylene fiber, or any combination thereof.

4. The device of any one of claims 1 -3 wherein the separator is a membrane, a mesh, a film or a foam.

5. The device of any one of claims 1 -4 wherein the container comprises the separator, and the separator comprises a membrane comprising glass wool, a hydrogel, polyethylene, polypropylene, polyvinyl chloride, polytetrafluoroethylene, nonwoven high density polyethylene fiber, or any combination thereof, and/or a foaming agent comprising a detergent, an amphiphile, a polyurethane, sodium lauryl ether sulfate, ammonium lauryl sulfate, a polyethylene foam, a hydrophilic fiber, or any combination thereof.

6. The device of any one of claims 1 -5 wherein the container is liquid impermeable and gas permeable.

7. The device of claim 6 wherein at least a portion of the container is air permeable.

8. The device of any one of claims 1 -7 wherein the container has pores extending from an interior wall to an exterior wall and configured for release of chlorine dioxide.

9. The device of any one of claims 1 -8 wherein the container comprises the separator; the chlorine dioxide precursor is in a first chamber of the at least two chambers; the quenching compound is in a second chamber of the at least two chambers, and the device is configured such that the separator will fracture upon application of pressure.

10. The device of claim 9 wherein the separator is a break seal.

11 . The device of claim 9 wherein the chlorine dioxide precursor is in a first frangible in the first chamber of the at least two chambers; the quenching compound is in a second frangible in the second chamber of the at least two chambers; and the device is configured such that the frangibles will fracture upon application of pressure.

12. The device of claim 11 wherein the first frangible and the second frangible are each an ampule or a pouch, and the chlorine dioxide precursor and the quenching compound are powders or liquids.

13. The device of claim 9 wherein chlorine dioxide precursor is in the form of a powder or microcapsules capable of releasing the chlorine dioxide precursor upon contact of the powder or the microcapsules with the optional diluent.

14. A gas generating and releasing device comprising: a substrate comprising a front surface, a back surface and a side surface; a gas generating film comprising: a chlorine dioxide precursor; an oxidizing agent or an acid; an optional diluent; and an optional desiccant or dehumidifying agent; an optional quenching compound; and an optional indicator configured to change color when exposed to chlorine dioxide gas to indicate whether gas has been generated, wherein the gas generating film is between the front and back surfaces of the substrate or is on an exterior surface of the front surface, the back surface or the side surface of the substrate.

15. The device of claim 14 wherein the substrate has an optional peelable layer, and the device is configured to generate chlorine dioxide when the substrate is bent or pressed and/or when the peelable layer is peeled away from the substrate.

16. The device of claim 14 wherein the substrate is a hang tag, a foam, or a film.

17. The device of any one of claims 1 -16 wherein the chlorine dioxide precursor comprises sodium chlorate, sodium chlorite, ammonium chlorite, a chlorite salt of a secondary amine, a chlorite salt of a tertiary amine, a quaternary ammonium chlorite, a trialkylammonium chlorite, or any combination thereof.

18. The device of any one of claims 1 -17 wherein the oxidizing agent or acid comprises an alpha-hydroxy alcohol, an acyl halide, an anhydride, boric acid, calcium chloride, a carboxylate of polyphosphate, carboxylic acid, citric acid, a condensed phosphate, a dialkyl phosphate, hydrochloric acid, malic acid, a metal salt, a mineral acid, a phosphosiloxane, a phosphate ester, phosphoric acid, a phosphosilicate, a phosphosilicic anhydride, a polyphosphate, sodium hydrogen ascorbate, sodium persulfate, sodium sulfite, sorbitan monostearate, sorbitol monostearate, sulfonic acid, sulfonic acid chloride, a sulfonic acid ester, tartaric acid, a trialkylsilyl phosphate ester, tetraalkyl ammonium polyphosphate, monobasic potassium phosphate, potassium polymetaphosphate, sodium metaphosphate, a borophosphate, an aluminophosphate, a silicophosphate, a sodium polyphosphate, potassium tripolyphosphate, sodiumpotassium phosphate, or any combination thereof.

19. The device of any one of claims 1 -18 wherein the diluent comprises sodium bicarbonate, a carbide, a clay, glass fiber, a metal oxide, a nitride, a silica gel, a silicate, silicon dioxide, water, a zeolite, or any combination thereof.

20. The device of any one of claims 1 -19 wherein the quenching compound comprises activated charcoal, carbon, humidity chips, compressed hydrophilic foam, compressed hydrophilic fibers, a superabsorbent polymer, a hydrogel, an osmotic material, an absorbent gelling material, a polyacrylic acid, an ethylene maleic anhydride copolymer, crosslinked carboxymethylcellulose, a polyvinyl alcohol copolymer, sodium bicarbonate and an acid, or any combination thereof.

21 . The device of any one of claims 1 -20 wherein the indicator comprises betacarotene, rifampin, Yellow #8, tetracycline, Red #40, Red #3, Blue #2, Evans blue, Green #3, Blue #1 , methylene blue, indocyanine green, betanin, beet juice, Blue #29, Blue #97 or Blue #104.

22. The device of any one of claims 1 -21 wherein the desiccant or dehumidifying agent comprises activated charcoal, alumina, an aluminosilicate, analcime, arginine, bauxite, calcium carbonate, calcium chloride, calcium sulfate, chabazite, charcoal, chondroitin sulfate, a clay, clinoptilolite, crystalline silica, gelatin, heulandite, glycoaminoglycan, magnesium sulfate, moisture-depleted silica gel, a molecular sieve, montmorillonite clay, natrolite, phillipsite, polylactic acid, potassium permanganate, pure silica, quartz, silica sand, a silicate, silicic oxide, silicon oxide, sodium chloride, sodium sulfate, stibite, a sugar, a zeolite, or any combination thereof.

23. The device of claim 22 wherein the desiccant or dehumidifying agent is embedded in or included in a mitigating layer comprised of calcium chloride, a cellulose, a clay, cotton, a hydrogel, a hydrophilic clay, a hydrophobic clay, a natural fiber, a nonwoven polymer, a non-powdered polymer, a powdered polymer, sawdust, silica gel, sodium hydrogen ascorbate, sodium sulfite, sponge particles, talcum powder, a woven polymer, a zeolite, or any combination thereof.

24. The device of any one of claims 1 -23 wherein the tangibles comprise a composite material, glass, onion skin glass, a plastic, a sealant comprising a low density polyethylene and oriented polypropylene coextrusion, or any combination thereof.

25. The device of any one of claims 1 -13 wherein the gas generating combination comprises from about 10 wt. % to about 35 wt. % of the chlorine dioxide precursor, from about 5 wt. % to about 40 wt. % of the oxidizing agent or from about 1 wt. % to about 10 wt. % of the acid, from about 15 wt. % to about 25 wt. % of the diluent, and from about 20 wt. % to about 60 wt. % of the desiccant or dehumidifying agent.