DK141921B - Microbiocidal agent for non-drug use. - Google Patents

Description

(S) \ Ra / (11) PUBLICATION MANUAL 141 921 DENMARK (61) lnt C | 3 A 01 H 59/00 '(21) Application No. 85Ο / 72 (22) Filed on 25 · Feb · 1972 (23) Race day 25 · f®b. 1972 (44) The increase submitted and _ p

the presentation document published on · JU1. Lyou

Dl THE RECTORATE FOR

PATENT AND TRADE MARKET (30) Priority granted from it

Feb 24 1971, 118520, US

(71) THE LOW CHEMICAL COMPANY, 929 East Main Street, Midland, Michigan, US.

(72) Inventor: Clarence Llewellyn Moyle, P.0. Box 58, Clare, Michigan, US:

Paul Andrew Wolf, 1500 East Fine River Road, Midland, Michigan, US.

(74) Plenipotentiary in the proceedings:

The engineering company Budde, Schou & Co.

(54) Microbicide for Non-drug Use.

The present invention relates to a microbiocidal agent for non-drug use, i.e. for use in the control of microorganisms such as bacteria, fungi and algae, which agent contains a dibromo cyanoacetamide similar to the formula

N s C - CBr2-C0-NHR

wherein R represents hydrogen or methyl, which agent is characterized in that it also contains a halide salt selected from alkali metal, alkaline earth metal, ammonium bromides and iodides.

2 141921

The dibromo-cyanoacetamide compounds used in the invention have considerable antimicrobial and disinfectant activity. Thus, 2,2-dibromo-2-cyanoacetamide is a potent and fast-acting antimicrobial agent in aqueous systems at concentrations as low as 0.5 parts per ml. million.

The water-soluble halide salts used in the composition of the invention are selected from alkali metal, alkaline earth metal and ammonium bromides and iodides, e.g. sodium, potassium, calcium, magnesium and ammonium bromides and iodides. In a more limited sense, such salts can be termed active disinfectants, especially when used in extremely concentrated solutions such as 10% and above, in which the osmotic pressure is an important factor. At the levels normally used for disinfection, the halide salts themselves show little or no antimicrobial effect, and in many cases they can even contribute the necessary ions to the microbial nutrition. In the agent of the invention, the water-soluble halide salts are used as a source of halide ions which, although having little or no detectable antimicrobial or disinfectant effect only under the conditions of use, greatly increase the disinfectant effect of the dibromo-cyanoacetamide compounds with which they are used.

It has been found that the combination of such dibromo cyanoacetamide compounds with aqueous bromide or iodide ions provides greatly increased disinfectant effect compared to the action of the individual components thereof. These results show increased and accelerated microbial destruction. Eg. has a combination of 10 parts by weight of 2,2-dibromo-2-cyanoacetamide and 90 parts by weight of sodium iodide microbial killing rates indicated in logarithmic units per more than 10 times the value that can be obtained with each component alone. The results obtained with the combination also show greatly increased antimicrobial net effect over a given period of time.

Thus, the agent of the invention can be used in conventional measures for the control of microorganisms. It is particularly useful when used in the presence of water, in aqueous preparations subjected to microbial attacks, either for disinfecting and preserving aqueous solutions and suspensions such as cutting oil emulsions, drilling oil emulsions, industrial wastewater, industrial cooling water, swimming pools, paper pulp slurries and the like. which is subject to attack by bacteria, fungi and / or algae, or for disinfection of solid surfaces that are subject to microbial infections such as walls, floors, pipes, sinks, project work, machinery, and containers, by application of aqueous disinfectants containing antimicrobial amounts of the active combination.

Under usual conditions, the destruction of microorganisms with a disinfectant requires contact between the organisms and the disinfectant for a certain period of time during which the organisms are destroyed. The rate of disinfection effect depends on several different factors, such as the nature of the substrate, the concentration of the disinfectant, the concentration and type of the organisms, the temperature, the age of the micro-growth and the like. The antimicrobial effect obtained within a given time of exposure under a particular set of conditions may also depend on such factors as the rate of reproduction of surviving microorganisms relative to the rate at which the disinfectant is removed from the system, the rate of introduction for new micropopulations, and the relationship between the disinfectant speed of action and concentration of disinfectant. For most disinfectants, the rate of antimicrobial action and the effect obtained within a given time span can be increased by using very high antimicrobial concentrations of the active antimicrobial agent.

The efficiency of the disinfectant dibromo-cyanoacetamide component is remarkably increased by the presence of the bromide or iodide component without any increase in the concentration of the dibromo-cyanoacetamide component. The results obtained in the practice of the invention can be characterized as synergism, since the net antimicrobial effect produced by using both components is greater than the additive result that could be expected from the activity of each component alone. However, since the agent of the invention provides excellent antimicrobial results when the halide component is used at concentrations well below the levels at which such salts have significant antimicrobial action, the results obtained with the agent of the invention can be characterized rather as an enhancement of action than a synergism. Since the agent of the invention provides increased rates of disinfecting activity, the results obtained with the agent of the invention can in practice also be characterized as accelerated antimicrobial activity.

4 141921

In practical use of the agent of the invention, an antimicrobial amount of a mixture of a dibromoacetamide compound and one or more halide salts is contacted with the microorganisms, their residence or their substrate in any convenient manner, this contact being carried out in the presence of water.

The exact antimicrobial amount to be used may vary depending on such factors as the organisms to be combated, the compounds specifically used, the ratio of the halide to the dibromo cyanoacetamide in the mixture and the antimicrobial action desired during a particular contact time. In general, good antimicrobial results can be obtained with concentrations of approx. 0.5 to 10,000 or even more parts by weight of the mixture per liter. million parts by weight of the finished aqueous composition. In a manner of use of the agent, the dibromo-cyanoacetamide compound and a water-soluble halide salt are added to an aqueous composition which is subjected to microbial infestation or infected with microorganisms to provide an antimicrobial amount of the mixture in the final aqueous composition. In another way, the ingredients are mixed together. water to provide an antimicrobial amount of the mixture therein, and the resulting aqueous mixture is applied to the microorganisms, their sites or substrates.

The ratios to be used between the dibromo cyanoacetamide and the halide salt can vary considerably. Usually at least 0.05 moles of halide ion are provided. moles of dibromo cyanoacetamide, and excellent results can be obtained with mixtures containing from ca. 3 to nearly 100% by weight of water-soluble halide salt component. In general, at least approx. 3 parts by weight of halide salt to 97 parts by weight of haloalkanoacetamide compound. The maximum amount of halide ion to be used with the dibromo cyanoacetamide is not critical for achieving highly accelerated rates of activity or increased antimicrobial activity. Thus, the maximum amounts of halide salt to be used depend on such factors as economics and the desired absolute amount of salt to be present after complete or complete disinfection. Generally, the amount of salt used in the mixture is such that an antimicrobial amount of the final aqueous composition contains less of the salt component than that required to achieve inhibition and killing of microorganisms at osmotic pressure under the same conditions and the salt is used. preferably in amounts at which the salt itself has no antimicrobial action under the same conditions. In a convenient process, the halide salt is used in an amount of from approx. 3 to approx. 99% by weight of the finished mixture and the best results are usually obtained with disinfectants, where according to the invention the halide salt is conveniently present and present in an amount of 20 to 97% by weight, based on the combined weight of the dibromo-cyanoamide and halide. The magnitude of the accelerating effect of the disinfectant is generally greater, the higher the halide concentration, and mixtures containing water-soluble halide salt from 40 to 95% have e.g. excellent accelerated antimicrobial activity.

By appropriate use, an aqueous composition subjected to microbial infestation is treated by the addition of a microbiocidal agent of the invention containing the halide salt or salts in sufficient quantity to provide a proportion of the halide salt from ca. 40 to approx. 95% by weight of the combination of halide salt and dibromo-cyanoacetamide.

The agent of the invention can be formulated as ready-to-use disinfectants with the addition of a suitable liquid carrier such as water, alcohols, liquid hydrocarbons and the like or finely divided solid carriers such as talc, bentonite or attapulgitles. An excess of the halide salt in excess of the amount required to achieve a desired enhanced antimicrobial effect is not detrimental and can serve as a carrier which even provides for any further accelerated activity. Such compositions may be prepared as direct application agents or as concentrates to be diluted or dispersed in a liquid carrier such as water, either before or during use. In general, the solid compositions have greater storage stability than the liquid solutions or suspensions, and solids containing the active combination of one or more dibromo-cyanoacetamides and one or more halide salts are highly preferred. Such solids preferably comprise a mixture of about 3 to approx. 99 parts by weight of the halide salt component and approx. 1 to approx. 97 parts by weight of the bromocanoacetamide component in intimate admixture with a surfactant dispersant. The agent in the form of a solid concentrate will usually contain from about 5 to approx. 99% by weight of the active mixture. The surfactant may include solid emulsifier such as finely divided bentonite, pyrophyllite, full soil, attapulgite, silica, other clay species and mineral carriers, as well as liquid and solid ionic and non-ionic wetting agents and dispersing agents, alkaline earth metal alkaline metal, alkaline earth metal, compound organic ester derivatives, compound ether alcohols, sucrose metal lovates, condensation products of alkylene oxides with phenols and organic acids, polyoxyethylene derivatives of sorbitan esters or sugar esters, mahogany soaps and the like. The solids may be prepared as finely divided solids in the form of powders or moist powders, granules, pellets, dispersible or soluble tablets adapted to disperse the active mixture rapidly when added to water. They may also include other additives such as deodorizers, perfumes, dyes and the like, as desired.

The agent loses its antimicrobial activity over a period of a few hours to a few days when dispersed in water at an alkaline pH of 8 to 14. The resulting compositions can then be discarded in the environment with relatively little detrimental effect or provided to facilities. microbiological treatment of wastewater. In addition to the halide and dibromo cyanoacetamide constituents, a preferred agent comprises sufficiently a solid water-soluble base, such as an alkali metal hydroxide, carbonate, bicarbonate, phosphate or borate or a buffer salt mixture which provides a pH of at least about 8 when dissolved or dispersed in water to provide an antimicrobial amount of the mixture therein.

The accelerated disinfection effect obtained by the agent of the invention serves to provide rapid disinfection, within a few seconds to one or two hours, while the presence of the water-soluble base serves to rapidly remove the disinfecting properties of the resulting disinfected aqueous composition again. . The exact amounts of the water-soluble base and disinfectant combination to be used in such compositions depend on such factors as the pH of the aqueous preparation to be disinfected, the specifically used basic substance, the micropopulation to be eradicated, and the shelf life of the preparation before being discarded. . In general, the composition should include sufficient water-soluble base to provide a pH of about 10 8 to approx. 10 in an aqueous composition when dissolved therein at a sufficient rate to provide from ca. 50 to about 500 parts of dibromo cyanoacetamide per million parts of the finished aqueous dispersion.

The following examples serve to illustrate the composition of the invention.

ΙΑ 1921 7

Example 1

The increased antimicrobial activity achieved with the agent of the invention is illustrated using a culture of Staphylococcus aureus in the logarithmic weight phase. An aqueous culture medium is prepared as follows:

Ingredients Quantity

Dicalium phosphate 2.3 g

Casamino acids 5.0 g

Uracil 5.0 mg Yeast extract 1.0 g

Saline 2.5 ml

Water up to 975 ml &

The saline solution contains 4 g of magnesium sulfate heptahydrate, 0.2 g of ferrous sulfate heptahydrate and 0.15 g of manganese sulfate monohydrate in 100 ml of water. The pH of the above solution is adjusted to 7.2-7.4 and the solution sterilized and aseptically mixed with 25 ml of sterile aqueous 10% glucose solution.

1 ml of an actively growing culture of Staphylococcus aureus in the above medium is used as inoculum or graft to 9.0 ml of sterile medium to which a test compound is added. The graft fluid contains approx. 1200 to 1800 million organisms per milliliter. Alik-vot parts are taken at time intervals after inoculation and plated to produce bacterial counts.

The organism counts obtained after 30, 60 and 120 minutes of exposure or exposure to the representative test compounds are listed in the table below.

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The above results illustrate the significant increase in the strength and acceleration of the disinfectant effect obtained with combinations containing from ca. 0.05 to approx. 10 moles of halide ion per moles of dibromo cyanoacetamide or from ca. 3 to approx. 91% by weight of halide salt in the combination.

Example 2 In a similar manner to the operation described above in Example 1, sodium iodide and 2,2-dibromo-2-cyanoacetamide are used against Staphylococcus aureus as a test organism. The mixtures are prepared in the culture medium by adding sufficient 2,2-dibromo-2-cyanoacetamide to provide a final concentration of 125 parts by weight of the antimicrobial agent per minute. million parts by weight of the finished dispersion, and adding varying amounts of sodium iodide to separate culture vessels, so as to provide a series of cultures containing the two components in different weight ratios. The bacterial counts are obtained after the organisms have been exposed for 5 minutes to the microbial mixtures listed in Table II below.

Table II

Experiment No. Weight Ratio of Average Organic Metal DBCA to Nal (Organisms per ml) 1 100/0 8 x 106 2 80/20 6.5 x 106 3 60/40 7 x 105 4 40/60 1.3 x 103 5 20 / 80 0 - 100 6 5/95 0-5 7 0/100 * 2.6 x 107

Sodium iodide at a concentration of 125 parts per million.

The average figures found at time zero are approx.

2.5 x 10 organisms per ml. The above results show the remarkable increase in rapid antimicrobial activity achieved by the use of the agent of the invention compared to sodium iodide alone, which even gives a slightly larger number at the count, or by 2,2-dibromo-2-cyanoacetamide alone.

U1921

Example 3 10

The procedure for example 2 is repeated using 62.5 parts of 2,2-dibromo-2-cyanoacetamide per liter. million parts finished dispersion. The initial bacterial counts show approx. 6.3 x 10 ml. The counts obtained after exposure times of 5 and 5, respectively.

35 minutes are listed in the table below.

Table III

The weight

Combine mixture between 5 min. 35 min.

ning limb DBCA / Nal count decrease count count decrease when cut by count% count% DBCA 62.5 ppm 100/0 6.3xl07 0 3.2xl07 49

Mixture 80/20 4.5x107 29 5.9x102> 99.9

Mixture 60/40 8.7x106 86 0-5> 99.9

Mixture 40/60 2.0x102> 99.9 0-5> 99.9

Mixture 20/80 0-5> 99.9 0-5> 99.9

Mixture 5/95 0-5> 99.9 0-5> 99.9

Nal 62.5 ppm 0/100 6.4x107 -2+ 6.8x107 -8+

Negative count reduction by count indicates increase by count.

Example 4

Similar operations are performed as described above in Examples 2 and 3, using a gram-negative sample organism, Aerobacter aerogenes, and an exposure time of 6 minutes. The average counts found in such operations where the organism is exposed to 2,2-dibromo-2-cyanoacetamide and sodium iodide at concentrations of 50 parts per million, 6.2 and 94 organisms per million, respectively. ml. After exposing the organism for 6 minutes to a medium containing 50 parts of 2,2-dibromo-2-cynaoacetamide and 12.5 parts of sodium iodide per The average organism count is between 200 and 350 organisms per million parts of the medium. ml. Culture containers containing 50 parts of 2,2-dibromo-2-cyanoacetamide and sufficient amounts of sodium iodide to provide weight ratios of the acetamide compound to the halide compound of 60/40, 40/60, 20/80 and 5/95 are nearly sterile after six minutes. having counts from 0 to 5 organisms per ml.

Example 5 11 141921

A series of synthetic powder detergents are prepared containing 2,2-dibromo-2-cyanoacetamide and sodium bromide either individually or in a combination containing 90% by weight sodium bromide. These detergent-containing agents also contain a linear sodium alkylate sulfonate as surfactant dispersant, sodium carbonate as excipient and sodium tripolyphosphate as sequestering agent and excipient. The agents are dispersed in water in an amount of 0.5 g of each agent of 100 ml of finished dispersion to obtain a variety of liquid compositions. 100 ml of each composition is seeded with 1 ml of an actively growing suspension of Escherichia coli, and aliquot portions are taken after 30 seconds of exposure and the decrease in bacterial count after 30 seconds of exposure is determined. In such operations, a composition containing 40 parts of sodium carbonate, 30 parts of sodium tripolyphosphate and 10 parts of the surfactant dispersant as well as 18 parts of sodium bromide is found to give exactly the same results as those obtained with a control composition containing the first three components mentioned above in the conditions set out above. but no sodium bromide. A composition containing 40 parts of sodium carbonate, 30 parts of sodium tripolyphosphate, 10 parts of the surfactant dispersant, and 2 parts of the bromocanoacetamide is found to give a decrease by counting less than one log during the indicated 30-minute period. Three compositions (A, B and C) containing 2 parts of 2,2-dibromo-2-cyanoacetamide and 18 parts of sodium bromide in admixture with 40 parts of sodium carbonate and (A) 10 parts of the surfactant, (B) 30 parts of sodium tripolyphosphate or ( C) 10 parts of the surfactant plus 30 parts of sodium tripolyphosphate are found to give diminished counts of 2.34, 2.19 and 2.45 logarithmic units, respectively.

Example 6

In similar operations as described above in Example 5, a variety of detergent compositions are dispersed which are dispersed in water. 100 g of each of the resulting dispersions are seeded with 1 ml of a 24 h culture of Escherichia coli. After 30 seconds of contact time, 1 ml of the grafted mixture is taken out and diluted with sterile deionized water to determine the count reduction.

In such operations, a dispersion containing 0.2% by weight of 12% sodium carbonate, 0.05% of linear sodium alkylate sulfonate, 0.15% of sodium tripolyphosphate, 0.09% of sodium bromide and 0.01% of 2,2-dibromo-2-cyanoacetamide is shown. say to give a count reduction of over 99% or more than 2.1 logarithmic units over the 30-minute exposure period. A composition containing the above ingredients in the same amounts in weight percent except that sodium abromide is omitted is found to give a count reduction of approx. 95.9% or 1.39 logarithmic units. A composition containing the first four of the above ingredients at the above concentrations and a control composition containing only sodium carbonate, the surfactant and sodium tripolyphosphate is found to give virtually identical results, count reductions below 82% or less than 0.75 logarithmic units, the latter two compositions showing colonies which are too numerous to be counted at the highest dilution.