KR910009391B1 - Method of sterizating by chlorine dioxide and apparatus of its - Google Patents

Abstract

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Description

Pollution surface treatment method and device

The accompanying Figure 1 shows an apparatus for carrying out the method of the invention.

The present invention relates to fungicide compositions containing chlorine dioxide gas and novel sterilizers.

As technical uses continue to be introduced for new materials that cannot be sterilized by radiation treatment, heat sterilization or exposure to liquid systems, there has been a need to develop other sterilization means.

The main modern method for this purpose is based on the use of gaseous chemicals. However, such chemical compounds must be used selectively since only those killing spores are classified as chemical fungicides. A wide range of antimicrobials are available, but most can kill resistant bacterial spores. Microbiocide can be specifically defined as killing the organism in which the suffix of “cide” is attached, for example, bactericide kills bacteria and antifungal kills fungi. Salvirus kills virus and sporidide kills bacteria and fungal spores. Since bacterial spores are the most difficult to destroy, only spore killers can be considered identical to chemical fungicides. Spore killers can be defined as chemicals that, if properly used, can destroy all forms of microorganisms, including bacterial spores and fungal spores and viruses.

(E.I. Dupont Co.)의 혼합물로 사용된다. 의약제품의 살균에 있어서, 산화 에틸렌 300-1200㎎/ℓ의 쳄버 농도에서 확실한 살균을 위해 일반적으로 130-140℉ 정도의 고온이 사용된다. 예비 습윤화 후 일반적으로 최소화 4.0시간의 가스노출 시간이 사용된다. 또한 산화 에틸렌은 유리, 도기, 경플라스틱과 금속과 같은 비다공성 물질상에서 보다는 종이 또는 직물과 같은 다공성 물질상에서 건성 포자를 사멸시키는데 더욱 효과적이다.Ethylene oxide gas and formaldehyde gas are used to sterilize many hospital and medical research facilities or work areas where heat sterilization or liquid sterilization cannot be easily performed. Formaldehyde, if used in high concentrations, may leave a solid para-formaldehyde residue. For this reason, formaldehyde is often avoided for the sterilization of precision equipment or environments where allergic reactions can occur. Unlike formaldehyde, ethylene oxide, which penetrates well into porous materials, is strongly absorbed by rubber and many plastics, so its vapor is not easily removed by simple ventilation. The publication of research papers on the mutagenicity and oncogenicity of ethylene oxide and formaldehyde, although not strictly prohibited, requires strict restrictions on the use of these compounds as fungicides. These limitations will significantly increase the costs associated with ethylene oxide sterilization. Apart from its potential health risks, ethylene oxide is difficult to control the concentrations and temperatures necessary for effective sterilization. Ethylene oxide is commonly used as a mixture with an inert gas such as fluorocarbon, since 3-80% concentration of ethylene is very explosive in air, for example 12% ethylene oxide and 88% Freon 12

(EI Dupont Co.) as a mixture. In the sterilization of pharmaceutical products, a high temperature, generally 130-140 ° F., is used to ensure sterilization at a chamber concentration of 300-1200 mg / l ethylene oxide. After prewetting, gas exposure times of at least 4.0 hours are generally used. Ethylene oxide is also more effective at killing dry spores on porous materials such as paper or textiles than on nonporous materials such as glass, pottery, light plastics and metals.

Gas phase disinfection in the rate method of C.W.Bruch and M.K.Bruch [M.A. Benarde, Ed., Marcel Decker, Pub., New York (1970), pages 149-207. Chlorine dioxide has long been known to be biologically active, and early studies have shown that chlorine dioxide has bactericidal properties and virus eradication and spore disappearance when used as an aqueous solution at a minimum concentration of about 0.20-0.25 mg / l. Known. Chlorine dioxide from W. J. masschelein; Chemical Properties and Environmental Effects of Oxygen Chlorine Compounds, R.G. Rice, ed., Ann Arbor Science Pub (1979); G.M. See Ridenour, et al., Water Sewage Works 96, 279 (1949). However, the most recent patents have demonstrated that aqueous chlorine dioxide alone is not sporicidal unless used in the presence of stabilizers. See Snyder, U.S. Patent No. 4,073,888. Sterilization methods using aqueous chlorine dioxide are difficult to formulate and handle, have all the general disadvantages associated with the use of aqueous disinfectants, including those that cannot be sterilized for instruments or materials that are sensitive to humidity, and precipitate upon drying.

Little is known about the gaseous chemistry of chlorine dioxide in air. At concentrations above about 10% (ie about 288 mg per liter), the compound is unstable and sometimes explodes, possibly due to impact or light catalyzed decomposition. For this reason, chlorine dioxide gas cannot be stored. In aqueous solutions of the same concentration, this is very stable. The chemical properties of chlorine dioxide dissolved in water are thought to be affected by hydrate production. At low temperatures (but above 0 ° C.), high concentrations of chlorine dioxide precipitate in hydrates of somewhat variable composition; Warming up can redissolve them. Chlorine dioxide in the warmed solution still has some water molecules accumulated in it. Such hydrates, of course, do not occur in the vapor state.

In general, the chlorine dioxide in the air will significantly change its chemistry because of its lack of effect due to polar solvents and the distance between each other in the gas phase. Eventually, only relatively small molecules will have sufficient vapor pressure to coexist with chlorine dioxide. Thus, compounds commonly used in natural water reactions (eg proteins, certain amino acids, humic and fulvinic acids) will not work in the vapor state.

Powder compositions formulated to release 10-10,000 ppm of chlorine dioxide gas are known (US Pat. No. 3,951,515). Free chlorine dioxide gas is known to be useful for killing bacteria and inhibiting fungal growth on fruit in shipment. Due to handling problems associated with chlorine dioxide, differences in the chemical properties of gas and solution states, and inconsistencies in the above-cited operations, chlorine dioxide gas has not proven useful at any concentration as a chemical fungicide.

Accordingly, it is an object of the present invention to use chlorine dioxide gas as a spore killer for many chemicals commonly used in chemical fungicides, ie medical and therapeutic devices and products.

Another object of the present invention is to use chlorine dioxide gas as a chemical fungicide under short exposure times and at ambient temperature, pressure and relative humidity.

It is also another object of the present invention to use chlorine dioxide as a chemical fungicide for materials such as medical devices sealed with gas-permeable packaging. The main object of the present invention is to use chlorine dioxide as a chemical fungicide on a non-permeable surface dried before sterilization.

Other objects, advantages and novel features of the invention will become apparent to those skilled in the art through the following description and appended claims.

The object of the present invention is achieved by exposing a microbially contaminated surface of a medical or dental instrument to an atmosphere containing an effective concentration of chlorine dioxide gas. Chlorine dioxide gas acts to sterilize its surface at ambient temperature, pressure and humidity. An effective concentration of chlorine dioxide gas is determined at a concentration at which explosion, corrosion and residue deposits are rarely a problem, and the gas can be used with devices that minimize the possibility of toxic concentrations of chlorine dioxide leaking into the working environment. have.

Chlorine dioxide gas can be prepared by any method known in the art. A preferred method is to disproportionate the sodium chlorite solution in the presence of an acid. Specifically, the dilute solution of aqueous potassium persulfate is treated with a dilute solution of aqueous sodium chlorite in an ambient temperature, that is, 20-30 ° C., in a closed reaction vessel. Rosenblatt, et al., J. Org Chem. See 28, 2790 (1963).

The temperature of the chlorine dioxide atmosphere formed in the space above the stirred reaction mixture can be controlled by external heating or cooling.

Preferred amounts of chlorine dioxide gas are injected into a suitable exposure chamber containing objects that have been adequately partially evacuated and sterilized. Chlorine dioxide gas is injected into the exposure chamber in a mixture of chlorine dioxide at a concentration used for sterilization with a carrier gas that is inert (ie, non-reactive with chlorine dioxide). The final internal pressure can be adjusted to one atmosphere or more using nitrogen, argon or other inert gas. At the end of the exposure period, the exposure chamber is evacuated and washed with filtered inert gas or air to remove chlorine dioxide. The exhausted chlorine dioxide can be easily destroyed by passing it through a reducing agent, for example passing the chlorine dioxide through a column of sodium thiosulfate fractions. The attached figure 7 shows an apparatus for carrying out the method of the invention. The exposure chamber 10 is connected to a controlled mixture of chlorine dioxide and nitrogen via a tube 11. Chlorine dioxide generated from the chlorine dioxide gas generating means 21 is introduced through the hole 14. Nitrogen gas is introduced through the orifice 20 from a suitable type of feeder. The vacuum pump 13 is connected to the interior of the exposure chamber 10 so that the interior of the exposure chamber is in a vacuum state during operation. The temperature gauge 15 is connected to the interior of the exposure chamber via a thermocouple to check the temperature during operation. The tube 12 is connected to all devices of the present invention, namely thermoelectric pairs, vacuum pumps and chlorine dioxide destruction devices. After the vacuum pump 13 lowers the pressure inside the exposure chamber 10, the valve 17 is closed to prevent the exhausted atmosphere from flowing back into the exposure chamber. A mixture of chlorine dioxide 14 and nitrogen 20 is introduced into the exposure chamber to effect sterilization. After the sterilization process is performed, air is injected into the exposure chamber so that the exposure chamber is restored to the pressure of atmospheric pressure.

The vacuum pump 13 then discharges the gas through the tube 16 out of the exposure chamber and provides it to the means 19 for destroying the chlorine dioxide gas in the exposure chamber. The means 19 includes a reducing agent, which acts to destroy chlorine dioxide when the reducing agent and the chlorine dioxide gas contact each other. The monitoring device 18 is located below the reducing device to monitor whether chlorine dioxide has been destroyed. The destroyed gas is discharged into the atmosphere through the vacuum pump 13. The composition of chlorine dioxide used in many sterilization methods is standard method, such as that of Wheeler, et al. [Micorchem. J., 23, 168-164 (1978)]. The atmospheric sample inside the exposure chamber is obtained via a septum-port using a gas-tight syringe. The volume of the sample varies with the expected chlorine dioxide concentration in its atmosphere. The atmosphere is preferably taken at the beginning or end of the exposure time. The contents of the syringe are injected into a suitable container, a cuvette containing the same amount of chemical that reacts to produce a color based on chlorine dioxide concentration. After completion of the reaction, the solution absorbance at the inherent wavelength is measured and the chlorine dioxide concentration is determined via a reference curve. The method is generally suitable for use in any known colorimetric method for chlorine dioxide analysis.

The spores of the standard experimental organism used to determine the effective sterilization concentration of chlorine dioxide gas were the spores of the Bacillus Substilis var. Niger (ATCC 9372). It is known that the spores of this microorganism are quite resistant to sterilization and are often used to measure the effectiveness of gas sterilizers. The Spore Problem of PMBorick and REPepper "Disinfection", [MABenarde, Ed., Marcel Decker, Pub., NY, (1970) P 85-102 ] AM Cook and M. W. Brown [J. Appl. Bact. 28, 361 (1965). Chlorine dioxide at this concentration is considered to be effective as a disinfectant if the initial 10 ⁵ -10 ⁷ spores show no concentration on nutrient medium when observed after 9 days of exposure to any concentration of chlorine dioxide. The standard suspension of spores of the Bacillus subtilisniger strain is J. Appl. As described by Dudd and Daley in Bacteril, 49, 89 (1980). Experimental paper strips for incubation are prepared by adding 0.2 ml of methanol suspension of spores to a 7 × 35 mm strip of pre-sterilized Whatman 3 mm paper in a glass petri dish. The paper is vacuum dried before use (30 ° C. and 30 in. Hg for 30 minutes) and left at ambient temperature and humidity (20-30 ° C., 40-60% relative humidity). The spores applied to each paper strip prepared in this way were 1.4 × 10 ⁶ spores.

Experimental pieces of metal foil were prepared by making small cups of square aluminum foil of 18 × 28 mm. They are sterilized in glass petri dishes. To each cup add 0.2 ml of methanol suspension of spores. The cup is dried at ambient temperature and left at ambient temperature and humidity prior to use. Spores added to each cup were approximately 1.4 × 10 ⁶ spores.

The foil and paper strips in the glass petri dish are left in the exposure chamber and exposed to various concentrations of chlorine dioxide in nitrogen over 1.0 hour. In general, the test is carried out using four to six identical Petri dishes at the same time for each. A range of gas concentrations is used to determine the effective sterilization concentrations for each surface.

After exposure, the paper strips are transferred to tubes in each sterile growth promoting medium and growth is observed at appropriate intervals. Aluminum foil cups are shaken with glass beads in water to remove spores. Spore suspension is contacted with a suitable medium preparation and growth is observed. If no growth is observed after the incubation period, this sterilization is due to the exposed material. Exposure of the strip of paper for about 1 hour to a low chlorine dioxide gas concentration of 40 mg / l at room temperature of about 27 ° C. and about 60% relative humidity provides nearly similar sterilization conditions for each strip, i.e. spore growth 9 days after culture This will not be observed. Surprisingly, considering the action of ethylene oxide, the spores proved to be no longer resistant when exposed to aluminum. Almost similar sterilization results were obtained for the foil cups at low chlorine dioxide gas concentrations of about 35 mg / l. After exposure of each substance to lower chlorine dioxide concentrations, including low concentrations of 11 mg / l, a number of tests were performed to obtain bactericidal effects.

The practice of the present invention is further described with reference to the following detailed examples.

Example 1

A 1000 ml two-neck round bottom flask was equipped with a dropping funnel and a magnetic stirrer. An inlet tube for nitrogen gas equipped with a glass wool filter and a needle valve is installed so that nitrogen is introduced below the surface of the reaction mixture. A needle valve is fitted to the outlet tube and installed to allow gas to pass from the reaction vessel into the exposure vessel.

A 2000 ml glass reaction water tube equipped with a septum stopper port, barometer, inlet port and outlet port is used as the exposure vessel. The outlet tube of the 1000 ml flask is connected to the inlet port of the exposure chamber.

In a typical experiment a 1000 ml flask was filled with 100 ml of 8% aqueous sodium chlorite solution under nitrogen. All valves are closed and 2.0 g of potassium persulfate solution dissolved in 100 ml of water is added with stirring. The reaction mixture is allowed to complete the generation of chlorine dioxide gas at 27 ° C. for 30-45 minutes.

3-6 spore coated paper strips or aluminum foil cups are placed in the exposure chamber, each placed in a separate glass petri dish. The exposure chamber is burned with nitrogen, sealed and evacuated (30 in. Hg). Open the outlet valve on the tube drawn from the reaction vessel to adjust the amount of chlorine dioxide gas entering the reaction vessel by looking at the pressure increase indicated on the barometer. The outlet valve is closed and the pressure in the exposure vessel is injected to nitrogen to 1 atm. The atmosphere in the exposed container is taken immediately by removing 0.5-2.0 ml of air through the septum using an airtight syringe. The concentration of chlorine dioxide is determined by Wheeler, et al., Microchem. J., 23, 160 (1978) method. After 60 minutes, the atmosphere is taken again. The exposure chamber is evacuated and refilled with filtered gas. Repeat the evacuation and refilling steps, open the exposure chamber and remove the contents under sterile conditions.

The paper strips are aseptically transferred to each typticase soy broth tube and incubated at 37 ° C. Observations to determine the presence of spores are made after 24 and 48 hours. After 48 hours, non-growing tubes are incubated for a week and observed every 24 hours. If no growth is observed after one week, record the paper strip as negative or sterilized.

After exposure, the foil is transferred to a separate tube containing 20 ml of sterile water and some glass beads. After vigorous stirring to remove and suspend spores, 0.1 ml of suspension is added to a pair of plates of trypticase soy agar. The plate is incubated at 37 ° C. and the paper strip is observed as described above. The experiment is also carried out on suitable control strips and foils. The results of 18 specific laboratories are summarized in Table 1 as Example 2-19.

TABLE 1

Exposure time-1 hour. Number of pieces of paper or foil cups in which growth was observed / exposure time Number of pieces of paper or foil cups.

The results of Example 2-19 demonstrated that chlorine dioxide at a concentration of at least 40 mg / l is effective for sterilizing paper strips contaminated with Bacillus subtilis raisin and thus effective for killing other microorganisms. Irregular growth occurrences observed in Examples 5, 7, 14 can be neglected due to experimental errors. More precise control of the experimental procedures and biological standards demonstrates effective sterilization over the entire concentration of the gas used. At similar concentrations, other porous organic surfaces such as rubber, gas-permeable plastics, sponges, plant materials, wood, etc. are expected to be sterilized without causing any degradation or residue sticking. A chlorine dioxide concentration of at least 35 mg / l is suitable for sterilizing aluminum foil contaminated with raisins. The growth observed on the foil in Example 6 is due to experimental errors, as it consistently shows sterilization results in the lower gas concentration range. From these results, other non-porous surfaces such as stainless steel, plated steel, metals such as aluminum and nickel, or nonporous plastics, medical or dental instruments or equipment made of porcelain, ceramics, or glass may not normally penetrate. It has been found that it can be easily sterilized under similar conditions.

Chlorine dioxide gas can also be used to successfully sterilize commercial spore strips sealed with gas permeable envelopes. A method that can be used to sterilize the materials is described below.

Example 20

Each 6 Spordi ^* paper spore strips (American sterile riser) containing a spore mixture of B. aureus subtilis and B. aureus sterostermo pyrus (NCTC 10003) and sealed with a sterile envelope of glassy paper. Coporation Sean Erie, Pa.) Is exposed to an atmosphere containing 50 and 100 mg / l chlorine dioxide gas as described in Example 1. The sealed spore strip is removed from the exposure chamber and incubated as described in Example 1 by opening under sterile conditions. Observation of growth after 9 days of culture indicates that the strip was effectively sterilized under the above conditions.

Chlorine dioxide effectively sterilizes contaminated surfaces sealed with gas-permeable container materials such as coated and uncoated paper, plastic plates, etc., without reacting distinctly with the container materials. The easy permeability of such containers of effective concentrations of chlorine dioxide can be applied to the sterilization of medical products which are preferably sterilized after packaging to ensure they are preserved in sterile state during shipment and storage.

Thus, it has been proved that chlorine dioxide gas is effectively a chemical fungicide for many dry surfaces under conditions of ambient temperature, pressure and humidity. Surfaces sealed with a gas-permeable material are also effectively sterilized under these conditions. Although effective concentrations of sterilization have been suggested by the methods of the above examples, lower concentrations may also be effective for sterilizing related substances.

Representative embodiments of the present invention have been described for the purpose of describing the present invention in more detail, and those skilled in the art will understand that various changes or modifications can be made without departing from the scope of the present invention.

Claims (10)

(a) drying the surface contaminated by microorganisms at ambient temperature and humidity; (b) removing most of the air in contact with the surface; (c) contacting the surface with an atmosphere containing a sterile amount of chlorine dioxide gas in an inert gas mixture, the inert gas being in an amount capable of adjusting the pressure of the gas mixture to about 1 atmosphere. A method for treating contaminated surfaces, which is present. The process of claim 1 wherein an atmosphere composed of at least about 11 mg / l chlorine dioxide gas is used. The method of claim 1 wherein the surface is made of a material that is impermeable to chlorine dioxide gas. 4. The method of claim 3 wherein the material is selected from the group consisting of metals, glass, porcelain, pottery or plastics. The method of claim 4, wherein the surface of the medical or dental instrument is sterilized. 6. The method of claim 1 or 5, further comprising sealing the surface with a gas permeable material prior to performing step (b). An exposure chamber 10, means for evacuating the exposure chamber 13, and means 21 for generating a sterile amount of chlorine dioxide gas, wherein the chlorine dioxide gas generating means inerts the chlorine dioxide gas. Apparatus for sterilizing instruments, characterized in that it is connected with a means (11) for mixing with the carrier gas and injecting into the exposure chamber. 8. The device of claim 7, wherein the device is a medical or dental device having a gas impermeable surface. The device of claim 7 or 8, wherein the inert carrier gas is nitrogen. 9. Apparatus according to claim 7 or 8, comprising means (19) for destroying chlorine dioxide gas by contacting chlorine dioxide gas with a reducing agent after the sterilization process is completed.

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