SYNERGISTIC ANTIMICROBIAL COMPOSITION

Abstract

A synergistic antimicrobial composition comprising: (a) diamine and (b) dithio-2,2-bis-benzmethylamide.

Claims

1. A synergistic antimicrobial composition comprising: (a) diamine; and (b) dithio-2,2-bis-benzmethylamide; wherein a weight ratio of the diamine to dithio-2,2-bis-benzmethylamide is from 10:1 to 1:10.

2. A synergistic antimicrobial composition comprising: (a) diamine; and (b) dithio-2,2-bis-benzmethylamide; wherein a weight ratio of the diamine to dithio-2,2-bis-benzmethylamide is from 9:1 to 1:10.

3. A method of inhibiting the growth of or controlling the growth of microorganisms in an aqueous medium comprising adding to the aqueous medium the composition of claim 1.

4. A method of inhibiting the growth of or controlling the growth of microorganisms in an aqueous medium comprising adding to the aqueous medium the composition of claim 2.

5. An aqueous medium comprising the synergistic antimicrobial composition of claim 1.

6. An aqueous medium comprising the synergistic antimicrobial composition of claim 2.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0005] As used herein, the following terms have the designated definitions, unless the context clearly indicates otherwise. The term antimicrobial compound refers to a compound capable of inhibiting the growth or propagation of microorganisms, and/or killing microorganisms; antimicrobial compounds include bactericides, bacteriostats, bacteriostatics, bacteriostatins, fungicides, fungistats, algaecides and algistats, depending on the dose level applied, system conditions and the level of microbial control desired. The term microorganism includes, for example, fungi (such as yeast and mold), bacteria and algae. The following abbreviations are used throughout the specification: ppm=parts per million by weight (weight/weight), mL=milliliter. Unless otherwise specified, temperatures are in degrees centigrade ( C.), and references to percentages are by weight (wt. %). Percentages of antimicrobial compounds in the composition of this invention are based on the total weight of active ingredients in the composition, i.e., the antimicrobial compounds themselves, exclusive of any amounts of solvents, carriers, dispersants, stabilizers or other materials which may be present. Lastly, all range value endpoints are inclusive and combinable (e.g. ranges expressed as from 10:1 to 1:10 and alternatively 3:1 and 1:3 may also include, for example 10:3).

[0006] As used herein, diamine(s) refers to N-(3-Aminopropyl)-N-dodecylpropane-1,3-diamine, cas #2372-82-9 and dithio-2,2-bis-benzmethylamide or DTBMA corresponds with cas #: 2527-58-4.

[0007] In some embodiments of the invention, a weight ratio of the diamine to dithio-2,2-bis-benzmethylamide (DTBMA) is from 10:1 to 1:10, alternatively from 9:1 to 1:9 and further alternatively from 3:1 to 1:3.

[0008] In some embodiments of the invention, the antimicrobial combination is useful for inhibiting microbial growth in an aqueous medium for example as an in-can preservative. The composition also is useful for controlling microorganisms in other aqueous media including but not limited to industrial water and water containing/contaminated media, such as cooling water, air washer, heat exchangers, boiler water, pulp and paper mill water, other industrial process water media such as: ballast water, wastewater, metalworking fluids, oil and gas, latex, paint, coatings, adhesives, inks, tape joint compounds, pigment, water-based slurries, personal care and household products such as detergent, filtration systems (including reverse osmosis and ultrafiltration systems), toilet bowel, textiles, leather and leather production system, or a system used therewith.

[0009] Typically, the amount of the biocide combinations of the present invention to control the growth of microorganisms is from 10 ppm to 5,000 ppm active ingredient. In some embodiments of the invention, the active ingredients of the composition are present in an amount of at least 20 ppm, alternatively at least 50 ppm, alternatively at least 100 ppm, alternatively at least 150 ppm, alternatively at least 200 ppm. In some embodiments, the active ingredients of the composition are present in an amount of no more than 2,000 ppm, alternatively no more than 1,000 ppm, alternatively no more than 500 ppm, alternatively no more than 400 ppm, alternatively no more than 300 ppm, alternatively no more than 250 ppm, alternatively no more than 200 ppm, alternatively no more than 100 ppm, alternatively no more than 50 ppm. Concentrations mentioned above are in a liquid composition containing the biocide combinations.

[0010] The present invention also encompasses a method for reducing, or inhibiting, or preventing microbial growth in the use areas described above, especially in in-can preservative applications, by incorporating the claimed biocide combination into the materials.

Examples

[0011] The synergism of the biocides combination of the present invention was determined using the method described by Kull, F. C., et. al in Applied Microbiology 9:538-541 (1961). The formula to calculate the synergy index (SI) is

Qa/QA+Qb/QB=SI

Where

[0012] QA=concentration of compound A in ppm, acting alone produced an end point (growth/no growth)
Qa=concentration of compound A in ppm, in the mixture, which produced an end point (growth/no growth)
QB=concentration of compound B in ppm, acting alone produced an end point (growth/no growth)
Qb=concentration of compound B in ppm, in the mixture, which produced an end point (growth/no growth)

[0013] In this study, biocide end point is defined as exhibiting at least 4 log bacterial or yeast reduction or maintaining a maximum 2 log bacterial or yeast count at the specified contact time. If end point could not be established, the highest concentration of biocide tested will be used as the end point for the calculation and the SI will be recorded in less than or < values

[0014] Synergism within two biocides is demonstrated when the SI has a value less than 1. The mixtures showed an additive effect if SI is equal to 1 and antagonistic if SI is greater than 1. The Minimum Inhibitory Test (MIC) is designed to evaluate the lowest concentration of a biocide, biocide blend or biocide combination to prevent bacteria, yeast, or fungi from growing in a defined broth. After incubation, the samples are rated based on visually detectable turbidity.

[0015] This test was carried out with a dilution factor of 1.5 for the biocides.

[0016] The following biocide products/mixtures were tested against two bacteria strains and one yeast:

Minimum Inhibitory Concentration (MIC) Testing Protocol

[0017] 1. Test samples were prepared in equal volumes in transparent containers. The biocide dilutions were done in tryptic soy broth (TSB) at pH of 7.3 for the bacteria and in malt extract broth (MEB) at pH 5.4 for the fungi strain. [0018] 16 samples per biocide product and species to be tested were prepared in duplicates by serial dilution with a dilution factor of 1.5. [0019] Per strain of micro-organism two samples not containing any biocide was added as a control. [0020] 2. Each test sample was inoculated with a microbe suspension to result in a level of 110.sup.6 CFU/ml in case of the bacteria species and 110.sup.5 CFU/ml for the fungi species respectively. [0021] Preparation of the microbe suspensions: [0022] Bacterial cultures:

TABLE-US-00001 Pseudomonas aeruginosa DSM # 939 ATCC# 15442 Staphylococcus aureus DSM # 799 ATCC# 6538 [0023] The cultures were maintained as glycerol stocks at 80 C. in cryovials, were thawed and then 100 l spread on TSA agar plates. After incubation for 1 day at 30 C. the strains were harvested with buffer pH 7.3. [0024] The concentration of cells was assessed by using a standard viable count technique. [0025] For the inoculum, dilutions were made in buffer pH 7.3. [0026] Yeast culture:

TABLE-US-00002 Candida albicans DSM #1386 ATCC# 10231 [0027] The cultures were maintained as glycerol stocks at 80 C. in cryovials, are thawed and then 100 l spread on MEA (malt extract agar) petri dishes. [0028] The yeast strain plates were incubated at 28 C. for 1-2 days then harvested with buffer pH 5.0. [0029] Based on total viable count results, the inoculum was prepared. [0030] 3. The incubation of test samples:

TABLE-US-00003 Bacteria 30 C. for 2 days Yeast 28 C. for 2 days [0031] 4. Reading was done visually by a growth/no growth rating. Growth of the microorganisms leads to turbidity after the incubation, clarity indicates no growth. The lowest concentration that shows no growth in the broth after incubation is taken as the MIC value.

[0032] The results of two biocides exhibiting synergy against the bacteria and yeast are presented in Tables 1-3.

TABLE-US-00004 TABLE 1 Biocidal efficacy and synergy of Diamine and DTBMA against Pseudomonas aeruginosa DSM # 939 Minimum Concentration Active (active ppm) weight ratio of to Inhibit Growth Synergy Diamine:DTBMA Diamine DTBMA Index Diamine alone 148 0 9:1 27 3 0.19 3:1 22 7 0.18 1:1 15 15 0.17 1:3 7 22 0.15 1:10 4 40 0.21 DTBMA alone 0 222

TABLE-US-00005 TABLE 2 Biocidal efficacy and synergy of Diamine and DTBMA against Staphylococcus Aureus DSM # 799 Minimum Concentration Active (active ppm) weight ratio of to Inhibit Growth Synergy Diamine:DTBMA Diamine DTBMA Index Diamine alone 44 0 9:1 27 3 0.74 3:1 10 3 0.38 1:1 10 10 0.73 1:3 3 10 0.57 1:9 2 18 0.93 DTBMA alone 0 20

TABLE-US-00006 TABLE 3 Biocidal efficacy and synergy of Diamine and DTBMA against Candida Albicans DSM # 1386 Minimum Concentration Active (active ppm) weight ratio of to Inhibit Growth Synergy Diamine:DTBMA Diamine DTBMA Index Diamine alone 148 0 9:1 18 2 0.13 3:1 33 11 0.30 1:1 22 22 0.30 1:3 16 49 0.44 1:9 3 27 0.20 DTBMA alone 0 148