WO2005117914A2 - Biocidal solution - Google Patents

Biocidal solution Download PDF

Info

Publication number
WO2005117914A2
WO2005117914A2 PCT/US2005/019665 US2005019665W WO2005117914A2 WO 2005117914 A2 WO2005117914 A2 WO 2005117914A2 US 2005019665 W US2005019665 W US 2005019665W WO 2005117914 A2 WO2005117914 A2 WO 2005117914A2
Authority
WO
WIPO (PCT)
Prior art keywords
solution
fac
biocidal
ph
concentration
Prior art date
Application number
PCT/US2005/019665
Other languages
French (fr)
Other versions
WO2005117914A3 (en
Inventor
Zsolt Kortvelyesi
Howard Mann
Gilbert Gordon
Original Assignee
Sterilox Technologies, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US57660604P priority Critical
Priority to US60/576,606 priority
Application filed by Sterilox Technologies, Inc. filed Critical Sterilox Technologies, Inc.
Publication of WO2005117914A2 publication Critical patent/WO2005117914A2/en
Publication of WO2005117914A3 publication Critical patent/WO2005117914A3/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients

Abstract

A biocidal solution containing a mixture of free available chlorine and chlorine dioxide. A method of producing such a biocidal solution using electrolysis or acidification is also provided. The biocidal solution can be used to disinfect a surface such as sterilize a medical device, decontaminate a food item, treat water, or reduce or eliminate biofilm.

Description

A BIOCIDAL SOLUTION

CROSS-REFERENCE TO RELATED APPLICATIONS The present application claims priority to U.S. Provisional Application No. 60/576,606 filed on June 4, 2004.

FIELD OF THE INVENTION The present invention relates to a biocidal solution containing free available chlorine and chlorine dioxide.

BACKGROUND OF THE INVENTION Electrochemically activated brine solutions can be very effective biocides, as the activated species in such solutions act to oxidize biological material or micro-organisms. Such biocidal solutions have numerous commercial uses such as sterilizing or disinfecting drinking water, treating food and food preparation apparatus, and sterilizing or disinfecting medical apparatus. These solutions typically utilize a much lower salt concentration and are also sometimes referred to as "superoxidised water solutions". The free available chlorine (FAC) content of an electrochemically activated brine solution is seen as the primary indicator of its biocidal efficacy and solutions with high levels of FAC can be readily produced. In general, the FAC content of an electrochemically activated brine solution contains a combination of chlorine species, more specifically aqueous chlorine (Cl2(aq)), hypochlorous acid (HOC1), and hypochlorite ions (OCL"). The pH of such a solution will have an effect on the proportion of these constituents in the solution. Chlorine dioxide does not contribute significantly to the FAC levels of an electrochemically activated brine solution. To produce electrochemically activated solutions having high levels of FAC, brine (or 'input solution') being passed into the electrolytic cell producing the solution needs to be of a high salt concentration. However, an input solution with a high salt concentration has a negative effect on equipment producing electrochemically activated solutions, due to the corrosive nature of the salt in the input solution. Further, the residual salt content of the electrochemically activated solution will also be high when the salt concentration of the input solution is high. This means that traditional electrochemically activated solutions with high FAC levels, because they have a high residual salt concentration, will also be corrosive against many devices that a user may wish to sterilize or disinfect. The FAC itself can also have a negative effect on materials requiring sterilization, for example, FAC will attack the polyurethane coatings on flexible endoscopes. FAC reacts rapidly with organic substances quickly consuming a substantial proportion of the active species (FAC). This is desirable when the organic substances are micro-organisms themselves. However, when the organic substances are, for example, residual protein material on an improperly cleaned or pre-washed medical device, the biocidal efficacy of the solution is quickly lost as the FAC reacts with the residual protein material, and is often lost before the device to be sterilized or disinfected has been sterilized or disinfected. Electrochemically activated solutions with relatively low FAC concentrations can still be effective broad spectrum biocides but, with respect to the materials being sterilized or disinfected, such solutions still suffer the negative effects, albeit to a lesser degree, associated with high level FAC solutions. However, lowering the FAC concentration (and hence also lowering the residual salt concentration) of the solutions to reduce their corrosive nature sacrifices biocidal efficacy. Chlorine dioxide (ClO2) has a long history of use as a disinfectant for the preparation of drinking water, and a shorter history of use as a disinfectant/sterilizing agent for medical devices. ClO2 is typically prepared for use in a healthcare setting by either the acidification or electrolysis of sodium chlorite solutions. In comparison to chlorine solutions, such as hypochlorous acid solutions, ClO2 solutions are less sensitive to organic contamination, that is, ClO2 tends to recycle itself to continue its biocidal activity. ClO2 solutions are also less susceptible to changes in solution pH and are more oxidising than chlorine solutions. However, depending upon the concentration, ClO2 solutions have potentially dangerous toxicological properties, possess greater hazards in storage and are more corrosive to metals. Because of such effects, use of ClO2 as a disinfectant/sterilizing agent for medical devices and other surfaces has been of limited beneficial value. Accordingly, there is an ongoing need for a biocidal solution that is not only effective but that also has a high level of compatibility with the devices and other surfaces they are to sterilize or disinfect.

SUMMARY OF THE INVENTION In an embodiment, the present invention provides a biocidal solution comprising free available chlorine and chlorine dioxide. In another embodiment, the present invention provides a method of disinfecting a surface by exposing the surface to a biocidal solution comprising free available chlorine and chlorine dioxide.

BRIEF DESCRIPTION OF THE DRAWINGS FIGURE 1 is a chart depicting the pH dependence of the rate of a FAC-ClO reaction. FIGURE 2 is a chart depicting the disinfection times as a function of disinfectant concentrations atpH 7.0. FIGURE 3 is a chart depicting the disinfection times as a function of disinfectant concentrations at pH 7.5 FIGURE 4 is a chart comparing sterile cylinders when different disinfectants and pretreatment methods are used. FIGURE 5 is a chart comparing the number of bacteria lost with different solutions and pretreatment methods.

DETAILED DESCRIPTION OF THE INVENTION As used herein, the term "FAC" refers to free available chlorine in a solution. It will of course be appreciated that other halides, when free in solution, also have biocidal efficacy and the present invention encompasses such other halides at the concentrations required to be equally effective as any stated concentration of FAC. A person skilled in the art will be readily able to determine such equivalent concentrations. Similarly, it will be appreciated that other halide dioxides, other than chlorine dioxide have biocidal efficacy and the present invention encompasses such other halide dioxides at the concentrations required to be equally effective as any stated concentration of FAC. A person skilled in the art will be readily able to determine such equivalent concentrations. The term "electrochemical cell" as used herein includes, unless the context otherwise requires, multiple electrochemical cells arranged either in series or in parallel, or a combination series-parallel arrangement. The invention has been described below primarily with reference to chlorine based acids and salts. It will of course be appreciated by those skilled in the art that the chlorine based acids and salts described herein could be replaced with other halide based acids and salts, and such other acids and salts are encompassed by the present invention. Similarly, although the invention has been described with reference to sodium salts, it should be understood that other metal salts can be used and a person skilled in the art will readily be able to determine which of such other salts are appropriate. In an embodiment, the present invention provides a biocidal solution comprising a mixture of ClO2 and a FAC such as elemental chlorine (Cl2), hypochlorous acid (HOC1) and/or hypochlorite ions (OCF). Without wishing to be bound by theory, it is believed that such mixtures form highly biocidal reactive intermediates which are stable for periods long enough to be useful to decontaminate medical devices, and other surfaces and items. Further, a biocidal solution according to the present invention can contain low concentrations of such reactive intermediates such that the solution is non-corrosive to many devices, surfaces, and items that may require sterilization, yet is still effective in biocidal terms. In a preferred embodiment, the present invention provides a biocidal solution having a chlorine dioxide concentration of about 0.1 to about 400 ppm and more preferably of about 80 to about 400 ppm and a FAC concentration of about 0.1 to about 350 ppm and more preferably of about 80 ppm to about 350 ppm. A biocidal solution containing a mixture of FAC and ClO2, according to the present invention, can be made by electrolysis or acidification. With respect to electrolysis, a biocidal solution of the present invention can be produced by passing a mixture of a chloride salt solution and a chlorite salt solution through an electrolytic cell or by separately electrolyzing a chloride salt solution and a chlorite salt solution and then mixing the two solutions together. It would of course also be possible to pass the chloride and chlorite salt solutions as a mixture or individually through several electrochemical cells, and such cells may be arranged either in series or parallel. More specifically, in an embodiment, an electrochemical cell used to produce a biocidal solution of the present invention has an anode chamber and a cathode chamber which produces respective anolyte and catholyte solutions, hi this embodiment, the biocidal activity of the biocidal solution is conferred to the solution primarily in the anode chamber. The method includes supplying to the cell a solution including a chlorite salt or other salt that will release chlorine dioxide when subject to electrolysis and a chloride salt. The method further comprises applying current to the cell to produce a biocidal solution comprising chlorine dioxide and FAC. Preferably, the concentrations of the chlorite salt and chloride salt and amount of current supplied are sufficient to impart to the biocidal solution an FAC concentration of 0.1 to 350ppm, more preferably 80- 350ppm, and chlorine dioxide concentration of 0.1 to 400ppm, more preferably 80- 400ppm. In another embodiment, the present invention provides a method of producing a biocidal solution in an electrolytic cell that comprises the steps of: (a) providing first and second electrolytic cells, each cell having an anode chamber and a cathode chamber which produce respective anolyte and catholyte solutions; (b) supplying to the first cell a solution including a chlorite (or other halite) salt or other salt that will release chlorine dioxide upon electrolysis and supplying to the second cell a solution including a chloride salt; (c) supplying electric current to the first cell to produce a first electrolyzed solution including chlorine dioxide and supplying electric current to the second cell to produce a second electrolyzed solution including FAC; and (d) mixing said first and second solutions to provide a biocidal solution comprising FAC and ClO2. Preferably, the biocidal solution has a FAC concentration of 0.1 to 350 ppm, more preferably 80- 350ppm, and a chlorine dioxide concentration of 0.1 to 400 ppm, more preferably 80- 400ppm. With respect to preparing a biocidal solution of the present invention by acidification, such a method involves acidifying a chlorite salt solution (or any other salt solution that produces chlorine dioxide when acidified) and mixing the acidified chlorite salt, which now includes ClO2 in solution, with an electrochemically activated chloride solution. A chlorate salt could also be used, as could other salts that produce chlorine dioxide when acidified. Specifically, in an embodiment, a method of producing a biocidal solution of the present invention includes acidifying a first solution including a chlorite salt or other salt that will release chlorine dioxide when subject to electrolysis and adding the first solution to a second solution of an electrochemically activated chloride solution to produce a biocidal solution comprising FAC and ClO2. Preferably, the chlorine dioxide concentration of the biocidal solution is 0.1 to 400pm and more preferably 80-350ppm and the FAC concentration of the biocidal solution is 0.1 to 350ppm and more preferably 80-300ppm. For all methods of the present invention, the person skilled in the art can readily determine appropriate concentrations for the chemical ingredients required to produce a biocidal solution of the present invention as well as the electrochemical conditions, for example appropriate current and pH, that should be applied to such ingredients. In a preferred embodiment of the invention, 80% of the biocidal active species is still present after 4 hours production. The pH of a biocidal solution of the present invention is preferably 6.1 to 6.3. In alternative embodiments of the invention, the pH may be any value between 5.8 to 7.5. The invention can also be effective outside these ranges. For example, pH values up to about 8 may also be used. When the pH is less than about 7.5, hypochlorous acid will be the primary contributor to the FAC component of the solution. At a pH of above about 7.5, hypochlorite ions will be the primary contributor. It is possible to characterize the solutions of the invention by, amongst other techniques, infrared analysis and high performance liquid chromatography (HPLC). A biocidal solution of the present invention provides improved biocidal performance in the presence of organic load, good materials compatibility with both plastics and metals, and acceptable toxicological profiles. A biocidal solution of the present invention can be used, for example, to sterilize and disinfect medical devices; treat food groups to make them safer for human consumption and improve shelf life of the commercial product by reducing microbial load naturally present or artificially introduced to the food groups; improve the shelf-life of non-food organic items such as flowers by reducing the microbial load on the subject that is to have its shelf-life extended; reduce or eliminate biofilm, such as biofilm within water lines by killing micro-organisms residing in the water lines; and otherwise decontaminate water.

EXAMPLES

Example 1 : Stability Measurement of CIO? and Cl2 Solutions of pure aqueous chlorine dioxide (ClO2) and free available chlorine (Cl2) were prepared and analyzed by amperometric titration to measure the concentrations of ClO2 and Cl2 as a function of time. By using amperometric titration, the concentrations of both ClO2 and Cl2 and the individual concentrations of ClO2 and Cl2 were measured directly. Solutions were more than 95% pure, which was sufficient to carry out preliminary kinetic experiments on the differences in reactivity (i.e. chemical stability) as a function of time at pH 7 and pH 9 in order to determine the pH for the continuing, preliminary experiments. 200 mg/L of ClO solution and 200 mg/L of Cl2 solution (1:1 ratio) were mixed in phosphate buffer. Samples from mixture were analyzed on the minutes and many hours time scale for starting components of ClO2 and Cl2. It was determined that at pH 7, the mixture is most reactive and at pH of 9, the mixture is least reactive.

Example 2: Effect of pH on Rate of Reaction of FAC* and C1Q2 50 to 200 mg/L of FAC (Cl2, HOC1, and OC1") solution and 12.5 to 200 mg/L of ClO2 solution (FAC/ClO2 ratio of between 1:1 ' and 8:1) are mixed in pH 6.5 and 7.5 phosphate buffers. Concentration of the reagents are measured by spectrophotometric analysis. TABLE 1 shows the wavelengths for the absorbance maxima and the molar absorbances (M^cm ) for the three reactants and the chlorite ion by-product.

FAC (Free Available Chlorine) represents the different chlorine species present in aqueous solution. The three species, that can be present in solution depending on the pH, are elemental chlorine TABLE 1 Molar absorbances of the reactants HOC1, OCT, ClO2 and the chlorite ion product at different wavelengths

Figure imgf000009_0001

TABLE 2 shows the half-life and tγ^ of chlorine dioxide at pH 7.5 at 1:1 and 4:1 FAC/ClO ratio and TABLE 3 shows the same parameters at pH of 6.5. The reaction of FAC and ClO2 is faster at pH of 7.5 than at 6.5 (at pH of 6.5, the reaction is about 5 to 6 times slower). Specifically, at pH 7.5 the slowest reaction (50 mg/L FAC & 12.5 mg/L ClO2) has a half-life of ~28 minutes, whereas at pH 6.5 the fastest reaction (200 mg/L FAC & 200 mg/L ClO2) has -39 minute half-life (t1/2 for 50 mg/L FAC & 12.5 mg/L ClO2 at pH 6.5 is ~113 minutes). As can also be seen from TABLE 2, the half-life of ClO2 increases with decreasing chlorine concentration. At higher concentrations, the chlorite ion slows the reaction which would result in a longer lifetime for chlorine dioxide.

TABLE 2 Half-life (t Y2) and the time required for 75% consumption (t 75%)of ClO2 at pH 7.5

Figure imgf000009_0002

(Ck), hypochlorous acid (HOC1), and hypochlorite ion (OC1"). TABLE 3 Half life (t Vi) and the time required for 75% consumption (t 75%)of ClO at pH 6.5

Figure imgf000010_0002

Based on these measurements, the order of each of the species in the rate law can be determined. This results in the following equation:

Figure imgf000010_0001

The products of the FAC-ClO2 reaction depend on the pH. With increasing pH, the amount of chlorite formed increases, which then further reacts with chlorine. For this reason, the chlorite concentration shows a maximum as a function of time — this is determined by the relative rates of the FAC-ClO2 and the FAC-chlorite reactions — and then starts decreasing. This is clearly observed at pH 7.5, but at 6.5 the chlorite formation is lower and its concentration remains practically constant during the measurement.

Example 3: Measuring the effects of pH, reactant concentrations, and temperature on the chlorine (FAC) - chlorine dioxide (C1Q2) reaction The FAC concentration is varied between 50 mg/L and 300 mg/L and the CIO2 concentration is changed between 12.5 mg/L and 200 mg/L. The ClO2 to FAC ratios varies between 1:1 to 1:24. The measurements are taken at two pH values, 6.5 and 7.5, set by using phosphate buffers, and at two temperatures, 22 °C and 35 °C. The purpose of these kinetic studies is to predict the stability of the FAC-CIO2 mixtures to be produced using electrolysis or by direct mixing of stable reactive components. The temperature study is carried out in order to determine the role that the increase or decrease of temperature has on the reaction. By comparing the rates of the reaction at different reactant concentrations, it is possible to determine the order with respect to a species in the rate law. TABLE 6 shows the rate constants for two FAC species at two temperatures. The rate constant for the chlorine dioxide - hypochlorite ion pathway is about three orders of magnitude higher, than for the chlorine dioxide - hypochlorous acid reaction. This means that at pH values at which CIO" is present, the reaction proceeds through this pathway almost exclusively. Thus, the rate of the overall reaction depends on the fraction of the FAC which is present as hypochlorite ion. The fraction of this species is increasing with increasing pH, resulting in faster reaction which is in agreement with our experimental findings.

TABLE 6 Comparison of the Rate Constants For the Different Reaction Pathways and Temperatures

Figure imgf000011_0001
In TABLE 6, the rate constants at 35 ° C also are shown. From this table it can be seen that at this higher temperature the reaction takes place approximately three times faster, which is due to the temperature dependence of the rate of the main reaction, between OC1" and CIO2. Higher disinfectant (FAC & CIO2) concentrations may be used which would result in higher initial disinfection, but the high concentration of these species may decrease rapidly due to the reaction between FAC & CIO2. This would mean that high concentration of the corrosive species would be present only for a short time, which would result in lower corrosion, thereby increasing disinfection efficiency and decreasing corrosion. In a preferred embodiment, 1-2 g/L ClO2 and FAC are used and after 2-3 hours, a relatively high (500-600 mg/L) CIO2 concentration is maintained but a low FAC (~50 mg/L or less) concentration is maintained. The ClO2 is less corrosive, thus, its high concentration would not contribute significantly to the corrosion but would provide sufficient disinfectant residual. Example 4: Preparing a Mixture of FAC and Chlorine Dioxide A 100 ml chlorite solution (a chlorine dioxide precursor solution) is prepared from solid sodium chlorite using distilled or deionized water. The chlorite solution contains approximately 24,000 mg/L of sodium chlorite. Equal volumes of the chlorite solution and a 1.0 M HC1 solution are mixed and the mixture is allowed to react for five minutes during which chlorine dioxide forms. The concentration of this chlorine dioxide solution, after the 5 minute reaction time with HC1, is approximately 6,000 mg/L ClO2. After this reaction time, this solution is used for preparing the Working Stock Solutions of ClO2. Working Stock Solutions are prepared from concentrated stock solutions of FAC (4,000 mg/L) and ClO2 (-6000 mg/L). TABLE 7 and TABLE 8 shows the compositions of the Working Stock Solutions. Each solution is brought to 50 mL volume with distilled water.

TABLE 7

Figure imgf000012_0001
Figure imgf000013_0001
Four different synthetic mixtures are prepared from the Working Stock Solutions as follows:

Figure imgf000013_0002

TABLE 6 provides the time required for 95%> of ClO2 to react with the FAC (t95»o).

TABLE 6

Figure imgf000013_0003

Example 5: Preparing a FAC-C1Q?_ Mixture Five test solutions are prepared on the apparatus described in GB patent 2352728 (Sterilox Medical (Europe) Limited). The hypochlorous acid-ClO2 mixture solution is prepared by passing a mixture of sodium chloride and sodium chlorite through one electrolytic cell. Final pH of the solution is 7.0. Example 6: Preparing FAC-C1Q?_ Mixture Separate solutions of hypochlorous acid and ClO2 are each prepared on the apparatus described in GB patent 2352728. The solutions are then mixed to form 5 test solutions. Final pH of the solution is 7.0.

Example 7: Preparing FAC-ClOτ_ Mixture Five test solutions are prepared by acidifying a sodium chlorite solution and mixing the acidified sodium chlorite solution with an electrochemically activated chloride solution. Again, solutions are prepared such that the final pH is 7.0.

Examples 8. 9. and 10: Preparing FAC-CIO? Mixture

Examples 7, 8, and 9 are each respectively the same as Examples 4, 5 and 6 but the solutions were produced such that their final pH is 7.8. Because of the higher pH, hypochlorite ions are the primary contributor to FAC for these solutions.

Example 11 : Preparing a Mixture of FAC and Chlorine Dioxide 1. Preparing Buffers and Ethanol Solution a. Buffer 1 (pH 6.5) 55.196g of NaH2PO »H2O and 170ml of NaOH solution (1.0M) are added to a 1L volumetric flask and the flask is filled to the mark with distilled water to produce a 6.5 pH buffer solution. b. Buffer 2 (pH 7.0) 55.196g of NaH2PO4 »H2O and 277ml of NaOH solution (1.0M) are added to a 1L volumetric flask and the flask is filled to the mark with distilled water to produce a 7.0 pH buffer solution. c. Buffer 3 (pH 7.5) 55.196g of NaH2PO4*H2O and 355ml of NaOH solution (1.0M) are added to a 1L volumetric flask and the flask is filled to the mark with distilled water to produce a 7.5 pH buffer solution. d. 5% Ethanol Solution 6.4 ml of 96% ethanol is diluted to 100 mL. 2. Preparing Chlorite Solution (chlorine dioxide precursor solution) A 100 ml chlorite solution (a chlorine dioxide precursor solution) is prepared from solid sodium chlorite using distilled or deionized water. The chlorite solution contains approximately 24,000 mg/L of sodium chlorite. 3. Preparing a Chlorine Dioxide (CIO2) Solution Equal volumes of the chlorite solution and a 1.0 M HCl solution are mixed and the mixture is allowed to react for five minutes during which chlorine dioxide forms. The concentration of this chlorine dioxide solution, after the 5 minute reaction time with HCl, is approximately 6,000 mg/L ClO2. 4. Preparing a Diluted Chlorine Dioxide Solution (600 mg/L) 30 mL of the pH 7 buffer solution and 10ml of the CIO2 solution are added to a 100 ml volumetric flask and the resultant solution is diluted to the mark with distilled water to produce a diluted chlorine dioxide solution (600 mg L). 5. Preparing Diluted FAC Solutions a. Diluted FAC solution (650 mg/L) 19mL of a FAC solution (bleach, pH 11, 4,000 mg/1) is diluted to 100 mL with distilled water to produce a diluted FAC solution (650 mg/1). b. Diluted FAC solution (600 mg/L) 30 ml of the 7.0 pH buffer solution and 17 mL of the FAC solution are added to a 100 mL volumetric flask and the resultant solution is diluted to the mark with distilled water to produce a diluted FAC solution (600 mg/1). 6. Preparing a FAC/CIO2 Mixture 5ml of the diluted FAC solution (600 mg/1) and 5 ml of the diluted ClO2 solution are mixed to produce a FAC/CIO2 mixture. The following different disinfectants are prepared and pretreatment methods are performed to assess biocidal efficacy:

Figure imgf000015_0001
Figure imgf000016_0001

Example 12: Efficacy of Solutions of Example 11 Against C. Sporosenes Inoculated Onto Porcelain Penicylinders 1. Preparation of Bacterial Culture Clostridium sporogenes (ATCC #3584, Manassas, Virginia) is maintained in 20 ml of soil extract nutrient broth containing 10% egg meet medium (SEEM) (Difco Laboratories) in a 25 x 150 mm screw-capped test tube incubated for 72±8 hours at 35±2°C. From this C. sporogenes bacterial stork, 0.8 ml is inoculated into 80 ml SEEM and incubated for 72±8 hours at 35±2°C. The suspension of C. sporogenes is decanted through moist sterile cotton in a glass funnel. This filtered suspension of C. sporogenes is used immediately to label cylindrical carriers (Fisher Scientific, Pittsburgh, PA). 2. Preparation of Cylindrical Carriers Cylindrical carriers are washed with Triton X-100 by swirling in a beaker and rinsing four times with tap water and twice with deionized water. These cylinders are then sterilized in a steam sterilizer at 121 °C for twenty minutes. The sterile cylinders are then dried in an oven at 60°C. When cool, these sterile cylinders are ready to be labeled with C. sporogenes. 3. Labeling and Drying of Cylindrical Carriers Approximately 30 ml of the cotton-filtered suspension of C. sporogenes is placed into a 100 ml glass beaker. Twenty-five (25) cylindrical carriers are added to the suspension. The cylinders are allowed to soak in the suspension for 60 seconds and then transferred to a double layer of filter paper in a petri plate and stood on end. The petri plates containing spore-labeled carriers are placed into a vacuum desiccator chamber above Drierite desiccant. A vacuum is drawn on the desiccator chamber for 20 minutes at 15 mm of Hg. The spore-labeled carriers are allowed to dry for 24±4 hours at ambient temperature. 4. Determining the Number of CFU/ml of Bacteria in the Suspension Used to Label Cylindrical Carriers Serial ten-fold dilutions of bacterial culture as used to label carriers are made as 1.0 ml into 9 ml portions of fluid thioglycollate medium (FTM) (Difco Laboratories) One (1.0) ml portions of several dilutions are placed into petri plates. Approximately 25 ml of molten nutrient agar (at 45 °C) are added to the petri plates and gently swirled to mix. The plates are incubated at 35±2°C for > 72 hours anaerobically. Colony counts are multiplied by the appropriate dilution factor to determine colony-forming units (CFU) per ml (CFU/ml) of bacteria in the culture suspensions used to label carriers. 5. Test Procedure Ten (10 ml) of the solutions of Example 11 are placed into sterile 25 x 150 mm capped test tubes and allowed to come to temperature in a 25±1°C water bath. One tube is prepared for each carrier. Using sterile flamed forceps, one labeled carrier is placed into each tube of disinfectant. After 15, 30, 60, 120, and 240 minutes of exposure, a sterile flamed nichrome wire hook is used to remove each spore-labeled carrier from the disinfectant and to place it into 10 ml of FTM contained in a plastic centrifuge tube with a rubber stopper. The tubes are agitated for 60 seconds on a vortex mixer and serial tenfold dilutions are made as 1.0 ml into 9 ml FTM. One (1.0) ml portions of several dilutions are placed into petri plates. Approximately 25 ml of molten nutrient agar (held at 45° C) are added to the petri plates and gently swirled to mix. The plates are allowed to solidify and then incubated anaerobically for > 72 hours at 35±2°C in a GasPak Anaerobic Chamber System (Becton Dickinson, Cockeysville, MD) Three C. sporogenes-labeled cylinders are tested per exposure time per test chemistry. All tubes are incubated for 3 days at 35±2°C and then scored for growth (+) or no growth (-). 6. Validation of Neutralization A sterile carrier is placed into 10 ml of a solution containing 200 mg/L of ClO2 and 200 mg/L of FAC in a buffer having 7.0 pH. The carrier is transferred from the disinfectant, with an additional 0.1 ml of disinfectant, to a test tube containing 10 ml of FTM. One serial ten-fold dilution is made as 1.0 ml into 9 ml of FTM and approximately 200 CFU of C. sporogenes (in 1.0ml of broth) are added to each tube. This is done twice. These tubes are incubated for 3 days at 35±2°C and then scored for growth (+) or no growth (-) of bacteria. Growth validated that the recovery process neutralizes any inhibitory activity of test-strength disinfectant. 7. Measure of the Number of Spores Per Labeled Cylindrical Carrier One bacteria labeled carrier is placed into 10 ml of FTM in a 18 x 11 mm plastic tube with silicone rubber stopper and agitated on a vortex mixer for 60 seconds. This is followed with a serial of ten-fold dilutions as 1.0 ml into 9 ml portions of FTM. One (1.0) ml portions of several dilutions are placed into petri plates. Approximately 25 ml of molten nutrient agar (at 45° C) is added to the petri plates and gently swirled to mix. The plates are allowed to dry and then incubated anaerobically for > 72 hours at 35±2°C. The colonies are counted and multiplied by the appropriate dilution factor to determine the number of spores on a spore-labeled carrier. This assay procedure is repeated for 5 cylinders. 8. Results Figure 4 shows a comparison of the sterile cylinders when different disinfectants and pretreatment methods are used. Figure 5 shows a comparison of the number of bacteria lost with different solutions and pretreatment methods. As indicated by Figures 4 and 5, a high level oxidizing solution capable of rapid disinfection is created using a mixture of FAC and ClO2. At pH of 7.0, a biocidal solution of 300 mg/1 of FAC and 300 mg/1 of ClO2 achieves the same level of disinfection as a 650 mg/1 solution of FAC. Due to the lower FAC concentration, however, this biocidal solution is less corrosive than a 650 mg/1 solution of FAC.

Example 13: Disinfection Times of a FAC-C1Q2 Mixture FIGURE 1 shows how the rate of the reaction of FAC and CIO2 changes with pH of 7.0 and 7.5. FIGURES 2 and 3 show the dependence of the disinfection time on the disinfectant concentrations at both pH values. At pH 7.0, the disinfection time is linearly dependent on the reciprocal of the bleach (FAC) concentration. However, in contrast to the role of bleach, the rate of disinfection is independent of the chlorine dioxide concentration. The absence of chlorine dioxide dependence can be described based on the previously determined rate law. The reaction between FAC and CIO2 takes place slower at pH 7.0, meaning that the amounts of intermediates are low as compared to pH 7.5 and their concentrations are controlled by the amount of OCl" present. Although not wishing to be bound by theory, from the concentration dependence at pH 7.5, the intermediates are thought to play role in the disinfection. These two facts together result in that the CIO2 concentration has no significant effect on the disinfection time. At pH 7.5, the concentration dependence for disinfection is different than at the pH 7.0. At the higher pH, the disinfection time depends on the concentration of both reactants. Although not wishing to be bound by theory, the unexpected effectiveness of the synthetic mixtures and the complex pH-concentration dependence of the disinfection time is thought to be due to the role of intermediates which are formed in these solutions. At higher pH (7.5), the concentration of hypochlorite ion is higher, resulting in an increase in the concentration of this intermediate. Although not wishing to be bound by theory, this increased amount of intermediate is thought to be responsible for the more effective disinfection at this pH value. By taking into account the previously measured concentration dependence, to achieve a 5 minute disinfection time at pH 7.0, the present invention provides a biocidal solution comprising 1,200 mg/L FAC and 200 mg/L CIO2. To achieve a 5 minute disinfection time at pH 7.5, the present invention also provides a biocidal solution comprising 300 mg/L of each disinfectant. This lower concentration would result in less toxic and less corrosive solutions. TABLE 8 provides additional biocidal solutions according to the present invention and their disinfection times. Solutions 1 and 2 have a slightly longer disinfection time than Solution 3. In each case, one of the sterilants is in lower concentration than in Solution 3.

TABLE 8 Composition of the Proposed Synthetic Mixtures And Their Estimated Disinfection Time

Figure imgf000020_0001

As shown from this Example, the efficacy of a FAC/CIO2 solutions at pH 7.5 increases more rapidly with increasing disinfectant concentration than at pH 7.0. For this reason if rapid disinfection is needed, a FAC/ClO2 solution at pH 7.5 may be used. But if the toxicity of the disinfectant solutions is more important, a FAC/CIO2 solution at pH 7.0 may be used, because the disinfectant concentrations can be decreased without a significant loss of their efficiency. However, the disinfection time is about 30 to 60 minutes when using a FAC/CIO2 solution at pH 7. Based on the test results, the time required for total disinfection (disinfection time), shows a different dependence on either ClO2 and FAC concentration at the two tested pH values (7.0 and 7.5). At pH 7.5 (the pH value which was tested in both cases) , the disinfection time depends on the square of both the FAC and ClO concentrations. It is thought that the pH changes the relative amount of intermediates and synergistic effects of the disinfectant. The foregoing description and examples have been set forth merely to illustrate the invention and are not intended as bemg limiting. Each of the disclosed aspects and embodiments of the present invention may be considered individually or in combination with other aspects, embodiments, and variations of the invention. In addition, unless otherwise specified, none of the steps of the methods of the present invention are confined to any particular order of performance. Modifications of the disclosed embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art and such modifications are within the scope of the present invention. Furthermore, all references cited herein are incorporated by reference in their entirety.

Claims

We claim:
1. A biocidal solution comprising a free available chlorine and a chlorine dioxide.
2. The biocidal solution of claim 1, wherein the free available chlorine is an elemental chlorine, a hypochlorous acid, a hypochlorite ion, or any combination thereof.
3. The biocidal solution of claim 1, wherein the concentration of the chlorine dioxide is about 0.1 to about 400 ppm.
4. The biocidal solution of claim 3, wherein the concentration of the chlorine dioxide is about 80 to about 400 ppm.
5. The biocidal solution of claim 1, wherein the concentration of the free available chlorine is about 0.1 to about 350 ppm.
6. The biocidal solution of claim 5, wherein the concentration of the free available chlorine is about 80 to about 350 ppm.
7. A method of producing the biocidal solution of claim 1, comprising: passing a mixture of a chloride salt solution and a chlorite salt solution through an electrolytic cell.
8. A method of producing the biocidal solution of claim 1 , comprising: separately electrolyzing a chloride salt solution and a chlorite salt solution; and mixing the chloride salt solution and the chlorite salt solution together.
9. A method of disinfecting a surface comprising: providing the biocidal solution of claim 1; and exposing the surface to the biocidal solution of claim 1 to disinfect the surface.
10. A method of sterilizing a medical device comprising: providing the biocidal solution of claim 1; and exposing the medical device to the biocidal solution of claim 1 to sterilize the medical device.
11. A method of reducing or eliminating biofilm comprising: providing the biocidal solution of claim 1; and exposing the biofilm to the biocidal solution of claim 1 to eliminate or reduce the biofilm.
PCT/US2005/019665 2004-06-04 2005-06-03 Biocidal solution WO2005117914A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US57660604P true 2004-06-04 2004-06-04
US60/576,606 2004-06-04

Publications (2)

Publication Number Publication Date
WO2005117914A2 true WO2005117914A2 (en) 2005-12-15
WO2005117914A3 WO2005117914A3 (en) 2007-04-19

Family

ID=35463335

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/019665 WO2005117914A2 (en) 2004-06-04 2005-06-03 Biocidal solution

Country Status (1)

Country Link
WO (1) WO2005117914A2 (en)

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010075477A3 (en) * 2008-12-22 2010-08-19 Oculus Innovative Sciences, Inc. Methods of treating or preventing biofilm associated infections with free available chlorine water
US8029740B2 (en) 2008-07-11 2011-10-04 The Invention Science Fund I, Llc Event-triggered self-sterilization of article surfaces
US8114346B2 (en) 2007-08-17 2012-02-14 The Invention Science Fund I, Llc Event-triggered ultraviolet light sterilization of surfaces
US8162924B2 (en) 2007-08-17 2012-04-24 The Invention Science Fund I, Llc System, devices, and methods including actively-controllable superoxide water generating systems
US8216173B2 (en) 2007-08-17 2012-07-10 The Invention Science Fund I, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US8460229B2 (en) 2007-08-17 2013-06-11 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having components that are actively controllable between transmissive and reflective states
US8585627B2 (en) 2008-12-04 2013-11-19 The Invention Science Fund I, Llc Systems, devices, and methods including catheters configured to monitor biofilm formation having biofilm spectral information configured as a data structure
US8647292B2 (en) 2007-08-17 2014-02-11 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having components that are actively controllable between two or more wettability states
US8706211B2 (en) 2007-08-17 2014-04-22 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having self-cleaning surfaces
US8702640B2 (en) 2007-08-17 2014-04-22 The Invention Science Fund I, Llc System, devices, and methods including catheters configured to monitor and inhibit biofilm formation
US8734718B2 (en) 2007-08-17 2014-05-27 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having an actively controllable therapeutic agent delivery component
US8753304B2 (en) 2007-08-17 2014-06-17 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having acoustically actuatable waveguide components for delivering a sterilizing stimulus to a region proximate a surface of the catheter
US8840873B2 (en) 2005-03-23 2014-09-23 Oculus Innovative Sciences, Inc. Method of treating second and third degree burns using oxidative reductive potential water solution
US8871278B2 (en) 2011-03-18 2014-10-28 Puricore, Inc. Stabilized hypohalous acid solutions
US9005263B2 (en) 2007-08-17 2015-04-14 The Invention Science Fund I, Llc System, devices, and methods including actively-controllable sterilizing excitation delivery implants
US9072726B2 (en) 2006-01-20 2015-07-07 Oculus Innovative Sciences, Inc. Methods of treating or preventing inflammation and hypersensitivity with oxidative reductive potential water solution
US9101678B2 (en) 2011-11-03 2015-08-11 Elwha Llc Heat-sanitization of surfaces
US20160152495A1 (en) * 2014-08-01 2016-06-02 Gordon & Rosenblatt, Llc Methods for eradicating biofilms from plumbing systems
US9381214B2 (en) 2011-03-18 2016-07-05 Puricore, Inc. Methods for treating skin irritation
US9474831B2 (en) 2008-12-04 2016-10-25 Gearbox, Llc Systems, devices, and methods including implantable devices with anti-microbial properties
EP3174393A4 (en) * 2014-07-30 2017-12-27 Ecolab USA Inc. Dual biocide generator
US10342825B2 (en) 2009-06-15 2019-07-09 Sonoma Pharmaceuticals, Inc. Solution containing hypochlorous acid and methods of using same

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1074515A2 (en) * 1999-08-06 2001-02-07 Sterilox Medical (Europe) Limited Electrochemical treatment of an aqueous solution
US6306281B1 (en) * 1999-11-30 2001-10-23 Joseph Matthew Kelley Electrolytic process for the generation of stable solutions of chlorine dioxide

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1074515A2 (en) * 1999-08-06 2001-02-07 Sterilox Medical (Europe) Limited Electrochemical treatment of an aqueous solution
US6306281B1 (en) * 1999-11-30 2001-10-23 Joseph Matthew Kelley Electrolytic process for the generation of stable solutions of chlorine dioxide

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BLOCK S.S.: 'Disinfection, Sterilization, and Preservation', 1991, LEA & FEBIGER, PHILADELPHIA pages 142 - 143, XP002205787 *

Cited By (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8840873B2 (en) 2005-03-23 2014-09-23 Oculus Innovative Sciences, Inc. Method of treating second and third degree burns using oxidative reductive potential water solution
US9072726B2 (en) 2006-01-20 2015-07-07 Oculus Innovative Sciences, Inc. Methods of treating or preventing inflammation and hypersensitivity with oxidative reductive potential water solution
US9782434B2 (en) 2006-01-20 2017-10-10 Sonoma Pharmaceuticals, Inc. Methods of treating or preventing inflammation and hypersensitivity with oxidative reductive potential water solution
US9149648B2 (en) 2007-08-17 2015-10-06 The Invention Science Fund I, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US8216173B2 (en) 2007-08-17 2012-07-10 The Invention Science Fund I, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US8282593B2 (en) 2007-08-17 2012-10-09 The Invention Science Fund I, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US8343086B2 (en) 2007-08-17 2013-01-01 The Invention Science Fund I, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US8162924B2 (en) 2007-08-17 2012-04-24 The Invention Science Fund I, Llc System, devices, and methods including actively-controllable superoxide water generating systems
US8366652B2 (en) 2007-08-17 2013-02-05 The Invention Science Fund I, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US8414517B2 (en) 2007-08-17 2013-04-09 The Invention Science Fund I, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US8460229B2 (en) 2007-08-17 2013-06-11 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having components that are actively controllable between transmissive and reflective states
US9005263B2 (en) 2007-08-17 2015-04-14 The Invention Science Fund I, Llc System, devices, and methods including actively-controllable sterilizing excitation delivery implants
US8647292B2 (en) 2007-08-17 2014-02-11 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having components that are actively controllable between two or more wettability states
US8706211B2 (en) 2007-08-17 2014-04-22 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having self-cleaning surfaces
US8702640B2 (en) 2007-08-17 2014-04-22 The Invention Science Fund I, Llc System, devices, and methods including catheters configured to monitor and inhibit biofilm formation
US8734718B2 (en) 2007-08-17 2014-05-27 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having an actively controllable therapeutic agent delivery component
US8753304B2 (en) 2007-08-17 2014-06-17 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having acoustically actuatable waveguide components for delivering a sterilizing stimulus to a region proximate a surface of the catheter
US8114346B2 (en) 2007-08-17 2012-02-14 The Invention Science Fund I, Llc Event-triggered ultraviolet light sterilization of surfaces
US9687670B2 (en) 2007-08-17 2017-06-27 Gearbox, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US8888731B2 (en) 2007-08-17 2014-11-18 The Invention Science Fund I, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US8343434B2 (en) 2008-07-11 2013-01-01 The Invention Science Fund I, Llc Event-triggered self-sterilization of article surfaces
US8029740B2 (en) 2008-07-11 2011-10-04 The Invention Science Fund I, Llc Event-triggered self-sterilization of article surfaces
US8585627B2 (en) 2008-12-04 2013-11-19 The Invention Science Fund I, Llc Systems, devices, and methods including catheters configured to monitor biofilm formation having biofilm spectral information configured as a data structure
US9474831B2 (en) 2008-12-04 2016-10-25 Gearbox, Llc Systems, devices, and methods including implantable devices with anti-microbial properties
WO2010075477A3 (en) * 2008-12-22 2010-08-19 Oculus Innovative Sciences, Inc. Methods of treating or preventing biofilm associated infections with free available chlorine water
US10342825B2 (en) 2009-06-15 2019-07-09 Sonoma Pharmaceuticals, Inc. Solution containing hypochlorous acid and methods of using same
US9392787B2 (en) 2011-03-18 2016-07-19 Puricore, Inc. Stabilized hypohalous acid solutions
US9414584B2 (en) 2011-03-18 2016-08-16 Puricore, Inc. Stabilized hypohalous acid solutions
US10034942B2 (en) 2011-03-18 2018-07-31 Realm Therapeutics, Inc. Stabilized hypohalous acid solutions
US9925217B2 (en) 2011-03-18 2018-03-27 Realm Therapeutics, Inc. Methods for treating inflammation associated with allergic reaction
US8871278B2 (en) 2011-03-18 2014-10-28 Puricore, Inc. Stabilized hypohalous acid solutions
US9381214B2 (en) 2011-03-18 2016-07-05 Puricore, Inc. Methods for treating skin irritation
US9421286B2 (en) 2011-11-03 2016-08-23 Elwha Llc Heat-sanitization of surfaces
US10179181B2 (en) 2011-11-03 2019-01-15 Elwha Llc Heat-sanitization of surfaces
US9101678B2 (en) 2011-11-03 2015-08-11 Elwha Llc Heat-sanitization of surfaces
EP3174393A4 (en) * 2014-07-30 2017-12-27 Ecolab USA Inc. Dual biocide generator
US20160152495A1 (en) * 2014-08-01 2016-06-02 Gordon & Rosenblatt, Llc Methods for eradicating biofilms from plumbing systems
EP3174832A4 (en) * 2014-08-01 2018-04-25 Gordon & Rosenblat LLC Methods for treating premise plumbing

Also Published As

Publication number Publication date
WO2005117914A3 (en) 2007-04-19

Similar Documents

Publication Publication Date Title
Venkitanarayanan et al. Efficacy of electrolyzed oxidizing water for inactivating Escherichia coli O157: H7, Salmonella enteritidis, and Listeria monocytogenes
AU742315B2 (en) Electrolytic synthesis of peracetic acid and other oxidants
FI86256C (en) Foerfarande Foer sterilisering of ytor, som aer through traengliga Foer gas with klordioxidgas.
Jeong et al. The effect of electrode material on the generation of oxidants and microbial inactivation in the electrochemical disinfection processes
AU717894B2 (en) Stabilized alkali or alkaline earth metal hypobromite and process for its production
EP0677990B1 (en) Compositions and uses thereof
US4681739A (en) Use of chlorine dioxide gas as a chemosterilizing agent
Guentzel et al. Reduction of bacteria on spinach, lettuce, and surfaces in food service areas using neutral electrolyzed oxidizing water
Landa-Solis et al. MicrocynTM: a novel super-oxidized water with neutral pH and disinfectant activity
US5683654A (en) Process to manufacture stabilized alkali or alkaline earth metal hypobromite and uses thereof in water treatment to control microbial fouling
US6878287B1 (en) Dental equipment and method of operating such equipment
Broadwater et al. Sensitivity of three selected bacterial species to ozone
Al-Haq et al. Disinfection effects of electrolyzed oxidizing water on suppressing fruit rot of pear caused by Botryosphaeria berengeriana
US20050139808A1 (en) Oxidative reductive potential water solution and process for producing same
US20040037737A1 (en) Method of and equipment for washing, disinfecting and/or sterilizing health care devices
Patermarakis et al. Disinfection of water by electrochemical treatment
RU2247143C1 (en) Malt production process
US6555055B1 (en) System for preventing and remediating biofilms in dental equipment
Diao et al. Electron microscopic investigation of the bactericidal action of electrochemical disinfection in comparison with chlorination, ozonation and Fenton reaction
US20040055896A1 (en) Biocidal solution
US6652889B2 (en) Concentrated aqueous bromine solutions and their preparation and use
Rahman et al. Electrolyzed water as a novel sanitizer in the food industry: current trends and future perspectives
US20100189805A1 (en) Electrochemically treated water, method and device for the production thereof, and the use thereof as a disinfection agent
US5696046A (en) Cold sterilant solution
Cursons et al. Effect of disinfectants on pathogenic free-living amoebae: in axenic conditions.

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase in:

Ref country code: DE

WWW Wipo information: withdrawn in national office

Country of ref document: DE

122 Ep: pct application non-entry in european phase