JPH0210714B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention uses specific hydroxy-substituted esters of thiolsulfonic acids to treat Legionella pneumophila, the causative bacterium of Legionnaires Disease.
pneumophila) in the water system. More specifically, the compounds 2-hydroxyethyl methanethiolsulfonate and 2-hydroxypropyl methanethiolsulfonate are used in commercial and industrial cooling water systems, cooling towers, and evaporative recovery systems where Legionella pneumophila may grow. It is useful as a disinfectant to inhibit the growth of this pathogen in water appliances, air cleaning systems, and other water systems. Legionnaires' disease is a severe and sometimes fatal pneumonia-like respiratory disease. The causative bacteria of this disease are
The disease was identified after an outbreak among people who attended a July 1976 American Legion meeting at the Bellevous Straft Hotel in Philadelphia. Of the 182 people affected by this outbreak,
29 people died. After a 1976 outbreak among its members who had traveled to Philadelphia, the U.S. Centers for Disease Control and Public Health Services (CDC) in Atlanta, Georgia conducted intensive efforts to determine the cause of this respiratory illness. It started. Since then, the disease has become known as "Legionaire's disease." Then CDC
confirmed that the causative bacterium was a Gram-negative bacterium and named it Legionella pneumophila.
Subsequent research by the CDC has shown that Legionella pneumophila is not a new species and is likely related to a disease that began in the late 1940s. For a general discussion of the pathogenesis of this disease, see Eickhoff's “Etiology of Legionnaires' Disease.”
[Ann.Inter.Med., Vol.90, pp.499-502 (1979)]
Please refer to During the CDC investigation, L. pneumophila was collected from cooling towers and evaporative condensers of air conditioning or chilled water systems in buildings or facilities that were involved in outbreaks of Legionnaires' disease. For example, see the Eickhoff paper cited earlier. Etiological data suggest that the infection may have resulted from inhalation of contaminated water aerosols originating from these sources. Although the exact route of transmission has not yet been determined, CDC recommends that cooling water systems, cooling towers, evaporative condensers, and air We believe it is prudent to take steps to control or inhibit the growth of this pathogen in cleaning systems and other water systems. Bacteria and other microorganisms are known to grow in cooling towers and other water systems, causing slime formation, equipment contamination, corrosion, bad breath, and other problems. It is therefore common practice to employ chemical treatments and other methods to control the growth of these problematic organisms. However, these control methods were usually not designed to completely eradicate these organisms, but only to maintain microbial growth at acceptable levels to minimize slime formation and other problems. On the other hand, in the case of pathogenic bacteria such as L. pneumophila, it is desirable to completely eradicate these organisms and to use treatment agents and methods that are economically and safely employable. Legionnaires' disease is caused by L. in cooling water systems and other water systems that can generate aerosols.
Since it was first known to be associated with the presence of pneumophila, studies have been conducted to determine the efficacy of various commercial fungicides commonly used to control other microorganisms in these types of water systems. However, these substances generally pose problems such as slime formation and handling problems, but are adequate to the extent necessary to control organisms that are normally non-phagocytic.
Most of the test substances were unable to provide the control necessary to eliminate L. pneumophila as a waterborne pest to an extent that could be safely and economically employed. For most commonly used substances, the concentrations of chemicals required to completely eradicate L. pneumophila with reasonable contact times are several times higher than those needed to control other organisms; The processing costs involved were economically unfeasible. Other substances that may inhibit the growth of this organism at reasonable concentrations have had other drawbacks, such as relatively high toxicity to fish and other aquatic organisms or significant foaming properties. This latter property makes these substances harmful to the environment or causes problems in the operation of cooling systems. For example, the material poly[oxyethylene (dimethylimino) ethylene (dimethylimino) ethylene
Dichloride] is useful for inhibiting algal and bacterial growth in industrial water systems. See, eg, US Pat. No. 3,771,989 to Pella et al. This specification states that this fungicide is 2.0ppm.
has been reported to completely inhibit the growth of several species of algae and cyanobacteria commonly found in cooling water systems. However, in standard in vitro experiments, L.
120 ppm of this fungicide was required to completely control or completely kill pneumophila. “Resistance of Legionella pneumophila to fungicides” by Harris et al. [Dev.Ind.
Microbiol., Vol. 21, pp. 265-271 (1980)]. Halogenated amides, such as 2,2-dibromo-3-nitrilopropionamide (DBNPA), are also useful as antimicrobial agents in cooling water systems and other water systems. For example, U.S. Pat. No. 3,647,610 by Wolf and “2,
2-dibromo-3-nitrilopropionamide,
Compound with slime formation inhibiting activity “[Appl.
Microbiol..Vol.24, No.4, pp.581-584 (1972)]
Please refer to DBNPA was proven to be more effective than many other fungicides in inhibiting the growth of L. pneumophila. This compound 4ppm
This is because it was completely killed after 2 hours of contact time. For example, see the report by Harris et al. cited earlier. However, now Dow Chemical Company (Midland, Michigan) has produced Dow Antimicrobial 7287 (20% active DBNPA) and Dow Antimicrobial 8536 (5% active DBNPA).
The cost of this compound, which is manufactured and sold under the trade name , makes it expensive to use even at this concentration. Furthermore, this compound, like many other compounds used in cooling water treatment, has a relatively high toxicity to fish. It has been demonstrated that L. pneumophila is highly sensitive to free chlorine. For example, Scalley et al.'s “Laboratory study of disinfectants against Legionella pneumophila” [Appl. Envir.
Microbiol., Vol.40, No.4, pp.697-700 (1980)]
Please refer to They found that 3.3 ppm of chlorine derived from calcium hypochlorite kills L. pneumophila by 100%.
found that it can be killed. However, as they point out, chlorine is particularly unstable in the presence of organic substances, which can quickly neutralize its potency. To obtain the free chlorine levels necessary to control L. pneumophila under actual service conditions, excessive amounts of calcium hypochlorite are required, resulting in significant Corrosive conditions will result. Additionally, wastewater containing high residual chlorine may be harmful to the environment. Other fungicides that have been reported to be effective in controlling L. pneumophila are a combination of N-alkyldimethylbenzylammonium chloride (12.5%) and bis(tri-n-butyltin) oxide (2.25%). It is. For example, Grace et al., “Sensitivity of Legionella pneumophila to three cooling tower fungicides” [Appl.Environ.Microbiol.
Vol. 41, No. 1, pp. 233-236 (1981)]. This paper reports that 2 ppm of this combination completely kills L. pneumophila in an aqueous medium in a contact time of 3 hours.
However, this type of quaternary ammonium compound is surface active and causes foaming problems in circulating cooling water systems as well as in other water systems. Additionally, quaternary ammonium compounds are generally highly toxic to fish, and heavy metal compounds such as organotin compounds in this combination are not necessarily acceptable in wastewater entering lakes, rivers, and other public waters. . In the paper cited above, Grace et al. also tested another compound widely used as a cooling water disinfectant, methylene bis(thiocyanate). They found that the minimum lethal concentration of this compound against L. pneumophila was 62 ppm with a contact time of 3 hours. This results in
The use of this compound would not be economically viable for the control of this fungus. In addition to the prior art fungicides outlined above, all of these compounds also have relatively high toxicity to fish. For example, as mentioned above, DBNPA, which shows comparatively good efficacy in suppressing the growth of L. pneumophila, is used in the "Technical Handbook for Dow Antimicrobial 7287 and Dow Antimicrobial 8536" published by Dow Chemical Company (1980). )
According to 96% of this compound ranged from 0.9 to 1.8 ppm in rainbow trout and bluegill salmon.
Time LC has a value of ₅₀ . This means that concentrations within this range of this compound will kill 50% of these fish after 96 hours of exposure in a static fish toxicity test. Of course, this compound degrades rapidly and is not permanently present in the water system.
In practice, the problem of fish death generally does not occur.
However, if wastewater from a cooling tower, for example, flows directly into a fish-inhabited lake or river without going through a wastewater treatment system, this or other fungicides with similarly high fish toxicity may be used. If it had to be used at the relatively high concentrations required for pneumophila, it would seem possible that fish would die. It is therefore an object of the present invention to provide a method for controlling the growth of L. pneumophila in water systems, which eliminates the drawbacks of the prior art methods. This and other objects, features, and advantages of the invention will become apparent as the description progresses. To accomplish the foregoing and related ends, the invention includes the features hereinafter fully described and particularly pointed out in the claims. Although the following description details certain specific embodiments of the invention, they are illustrative of only a few of the various ways in which the principles of the invention may be employed. In summary, we use 2-hydroxyethyl methanethiolsulfonate (HEMTS) or 2-hydroxypropyl methanethiolsulfonate (HPMTS) as fungicides alone or in combination with each other or other fungicides. It has been found that the objects and advantages mentioned above are thereby achieved. When these compounds are used to treat water systems, the killing dose that completely inhibits Legionella pneumophila (100% lethal) is much greater than that of other fungicides used in prior art methods to control this fungus. low. Furthermore, at least one of these two substances has been shown to be relatively non-toxic to fish. Furthermore, these compounds are not corrosive to structural materials when used at the low concentrations required to control L. pneumophila. The bactericidal agent of the present invention is a 2-thiol sulfonic acid.
It is a type of compound that can be described as a hydroxyalkyl ester. One method for producing this type of compound is by Batskuman et al. in U.S. Pat. No. 3,859,322.
It is stated in the specification of the No. The process consists of reacting an alkali metal salt of thiolsulfonic acid with a 1,2-epoxide in the presence of an organic acid. Preferred compounds of the invention can be prepared by reacting sodium methanethiol sulfonate with ethylene oxide or propylene oxide in the presence of acetic acid as described in this patent. These compounds are further characterized by the names 2-hydroxyethyl methanethiolsulfonate and 2-hydroxypropyl methanethiolsulfonate, respectively, and have the structure: 2-Hydroxyethyl methanethiolsulfonate 2-Hydroxypropyl Methanethiolsulfonate When these compounds are used to inhibit the growth of Legionella pneumophila in accordance with the teachings of the present invention, suitable amounts range from 0.1 to 2.5 ppm of water.
The preferred amount of water is in the range of 0.25 to 10 ppm. Of course, higher amounts of the compound may be used without any deleterious effects, but these relatively high amounts increase operating costs and limit practical benefits. Both of these compounds are water soluble and compatible with many other water soluble disinfectants commonly used in the treatment of water systems such as circulating cooling water systems. They can therefore be formulated with other compatible bactericidal, algicidal or fungicidal agents to easily provide broad spectrum microbial control in a single formulation. One of these compounds, 2-hydroxypropyl methanethiolsulfonate, has been found to be relatively non-toxic to fish.
For example, a solution containing 80% 2-hydroxypropyl methanethiolsulfonate gave a 96 hour LC ₅₀ of 78 ppm for bluegill sunfish and a 96 hour LC ₅₀ of greater than 56 ppm for rainbow trout. Such concentrations are much higher than those required to achieve complete control of L. pneumophila. Therefore, the use of this compound for the treatment of water systems poses less harm to the aquatic environment than that posed by other fungicides commonly used for the treatment of these systems. The following specific examples are provided to more fully describe the nature of the invention. It will be understood, however, that the invention is not limited to the specific terms or details set forth in these examples, except as such limitations are expressly stated in the claims. Example 1 The efficacy of the compound 2-hydroxyethyl methanethiolsulfonate in inhibiting the growth of the bacterium Legionella pneumophila was tested according to the following test record. Legionella pneumophila (Philadelphia strain, serological group 1), provided by the Centers for Disease Control and Prevention (Atlanta, Georgia) to Methodist Hospital (Memphis, Tennessee), where this study was conducted, was first treated with 1% Isovitalex (BBL) and 1% The cells were grown and maintained on Mueller-Hinton agar supplemented with % hemoglobin, then grown and maintained on FG agar at 35° C., PH 6.9 and 2.5% CO ₂ . To prepare the test inoculum, the bacteria were grown on FG agar plates for 72 hours;
Resuspended in 0.85% saline in distilled water at pH 6.9.
Cell concentration was adjusted to 6×10 ⁸ /ml. A diluted stock solution of 2-hydroxyethyl methanethiol sulfonate was prepared using a sterile 0.85% diluted stock solution containing 1000 mg/ml of this compound.
% NaCl was freshly prepared immediately prior to testing by weighing a sufficient amount to prepare a liquid stock solution.
Sterile stock solution 0.85% so that if 1.0ml of inoculum is added to the contact bottle this will contain a total of 100ml
Added to saline solution. Tests were conducted at a contact temperature of 24° C. with contact times of 2 and 8 hours. A 4 mm loopful from each contact bottle was then smeared onto FG agar plates, followed by incubation at 35° C. for 10 days under 2.5% CO ₂ . The number of colonies on each plate was counted at the end of the culture period. The results are summarized in Table 1. The following numbers were used to explain the results. 4 = Number of colonies on collection plate 300 or more 3 = Number of colonies on collection plate 151-300 2 = Number of colonies on collection plate 51-150 1 = Number of colonies on collection plate 1-50 0 = Growth None Table 1 Suppression of L. pneumophila by 2-hydroxyethyl methanethiolsulfonate

[Table] These results indicate that L. pneumophila was highly inhibited by the addition of only 0.25 ppm of 2-hydroxyethyl methanethiolsulfonate, and completely inhibited by 0.5 ppm of this compound after only 2 hours of contact time. It shows. Example 2 Using the same method as described in Example 1, the compound 2-hydroxypropyl methanethiolsulfonate was evaluated for its efficacy in inhibiting L. pneumophila growth. The results are shown in Table 2. The numerical values used to explain the degree of inhibition are the same as those used in Table 1.

[Table] These tests showed that the growth of L. pneumophila was highly inhibited with a contact time of only 2 hours by a concentration of 0.5 ppm of 2-hydroxypropyl methanethiolsulfonate, and completely inhibited after a contact time of 8 hours. It shows that A 2-hydroxypropyl methanethiolsulfonate concentration of 1.0 ppm resulted in 100% killing of L. pneumophila after only 2 hours of contact time. Example 3 The following compounds or mixtures of compounds commonly used in the treatment of cooling water were evaluated by the same method as described in Example 1. The minimum inhibitory concentration of each compound required to kill Legionella pneumophila in as little as 2 hours of contact time is shown in Table 3. The results for the compounds of the invention 2-hydroxyethyl methanethiolsulfonate (HEMTS) and 2-hydroxypropyl methanethiolsulfonate (HPMTS) are entered in the same table for comparison. Bactericidal agent A: Potassium N-methyldithiocarbamate 14.7 parts Disodium dianodithioimide carbonate
20.3 parts Fungicide B: Potassium dimethyldithiocarbamate Fungicide C: 2,2-dibromo-3-nitrilopropionamide Fungicide D: Poly[oxyethylene (dimethylimino) ethylene (dimethylimino) ethylene dichloride]

[Table] These tests are based on methanethiol sulfonic acid 2
-Hydroxypropyl and methanethiol 2-hydroxyethyl sulfonate clearly shows that it is significantly superior to other commonly used fungicides in inhibiting the growth of Legionella pneumophila in aqueous media. Having described certain embodiments of the invention,
The invention is not limited to these as many modifications may be made and it is therefore intended that all such modifications which are within the true spirit of the invention be encompassed within the scope of the following claims. It will be understood.

Claims (1)

[Scope of Claims] 1. Contacting Legionella pneumophila with an ester selected from the group consisting of 2-hydroxyethyl methanethiolsulfonate and 2-hydroxypropyl methanethiolsulfonate in an amount sufficient to suppress the growth and proliferation of Legionella pneumophila. A method for inhibiting the growth and proliferation of Legionella pneumophila in a water system, comprising: 2. The method of claim 1, wherein the ester is 2-hydroxyethyl methanethiolsulfonate. 3. The method of claim 1, wherein the ester is 2-hydroxypropyl methanethiolsulfonate. 4. An ester selected from the group consisting of 2-hydroxyethyl methanethiolsulfonate and 2-hydroxypropyl methanethiolsulfonate in an amount sufficient to inhibit the growth and proliferation of Legionella pneumophila bacteria in commercial and industrial cooling. Consisting of adding to the water of the water system,
A method according to claim 1. 5. The method of claim 4, wherein the ester is 2-hydroxyethyl methanethiolsulfonate. 6. The method of claim 4, wherein the ester is 2-hydroxypropyl methanethiolsulfonate. 7 Adding an ester selected from the group consisting of 2-hydroxyethyl methanethiolsulfonate and 2-hydroxypropyl methanethiolsulfonate to the water of the air cleaning system in an amount sufficient to inhibit the growth and proliferation of Legionella pneumophila bacteria. Claim 1 consisting of
The method described in section. 8. The method of claim 7, wherein the ester is 2-hydroxyethyl methanethiolsulfonate. 9. The method of claim 7, wherein the ester is 2-hydroxypropyl methanethiolsulfonate. 10 An amount of an ester selected from the group consisting of 2-hydroxyethyl methanethiolsulfonate and 2-hydroxypropyl methanethiolsulfonate in an amount sufficient to inhibit the growth and proliferation of Legionella pneumophila bacteria is added to the evaporator of a cooling and air conditioning system. 2. A method according to claim 1, comprising adding to the water in a condenser. 11 The ester is methanethiol sulfonic acid 2-
Claim 10, which is hydroxyethyl
The method described in section. 12 The ester is methanethiol sulfonic acid 2-
Claim 1 which is hydroxypropyl
The method described in item 0.