US20070203126A1 - Synergistic Mixtures of O-Phenylphenol and Dazomet - Google Patents

Synergistic Mixtures of O-Phenylphenol and Dazomet Download PDF

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US20070203126A1
US20070203126A1 US11/677,618 US67761807A US2007203126A1 US 20070203126 A1 US20070203126 A1 US 20070203126A1 US 67761807 A US67761807 A US 67761807A US 2007203126 A1 US2007203126 A1 US 2007203126A1
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ppm
naopp
phenylphenol
ratio
biocide
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Paul Carlson
H. Nehus
Jodi Martin
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Lanxess Corp
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Verichem Inc
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Assigned to VERICHEM, INC. reassignment VERICHEM, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MARTIN, JODI L., CARLSON, PAUL E., NEHUS, H. EDWIN
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    • C—CHEMISTRY; METALLURGY
    • C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
    • C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
    • C02F1/00—Treatment of water, waste water, or sewage
    • C02F1/50—Treatment of water, waste water, or sewage by addition or application of a germicide or by oligodynamic treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • C—CHEMISTRY; METALLURGY
    • C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
    • C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
    • C02F2103/00—Nature of the water, waste water, sewage or sludge to be treated
    • C02F2103/02—Non-contaminated water, e.g. for industrial water supply
    • C02F2103/023—Water in cooling circuits

Definitions

  • This invention relates to synergistic mixtures of o-phenylphenol and/or its sodium salt with tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione commonly used in cement admixtures and slurries.
  • O-phenylphenol and Sodium orthophenylphenate are used extensively as antimicrobial agents in various industrial applications such as preservation of various materials including paints, adhesives etc. as well as to control unwanted microorganisms found in various process waters such as cooling water, paper mills and petroleum production.
  • Microbiological growth can cause contamination of products that requires the use of preservatives, as well as process waters, where Antimicrobials are required to prevent contamination.
  • Preservatives are required for a broad range of products including but not limited to adhesives, cosmetics and toiletries, disinfectants and sanitizers, leather, metalworking fluids, paints and coatings, plastics and resins, latex polymers, textiles and wood. Failure to preserve these products adequately will result in spoilage and loss of the materials to be preserved and will result in an economic loss. Similarly, microbiological growths can have dire consequences if process waters are not adequately treated. Process waters include but are not limited to: industrial recirculating water, paper products and paper, petroleum production and leather tanning.
  • This invention includes synergistic ratios of aqueous suspensions of orthophenylphenol or Sodium orthophenylphenate with the following chemical antimicrobials:
  • any ratio of OPP to the other antimicrobial within the range of 1%-99% to 99%-1% by weight may demonstrate a synergistic effect to some degree, but we prefer to use the most efficient combinations, which may include a wide range of ratios, as will be seen below.
  • Orthophenylphenol was found to produce synergistic blends with other antimicrobials.
  • the synergistic blends were determined using a dose protocol.
  • the actives were evaluated in synthetic white water with pH values of 5.5 and 8.0.
  • the materials were tested against an artificial bacterial consortium containing approximately equal numbers of six bacterial strains. Although the test strains are representative of organisms present in paper mill systems, the effect is not limited to these bacteria.
  • Two of the strains were Kiebsiella pneumoia (ATCC 13883) and Pseudomonas aeruginosa (ATCC 15442).
  • the other four strains were isolated from papermill systems and have been identified as Curtobacterium flaccumfaciens, Burkhlderia cepacia, Bacillus maroccanus, and Pseudomonas glethei. Each strain was inoculated at 37° C. overnight, then suspended in sterile saline. Equal volumes of each strain were then combined to prepare the consortium. The bacterial consortium was distributed into the wells of a microtiter plate in the presence or absence of various concentrations of the active materials. The microtiter plates were incubated at 37° C. Optical density (O.D.) readings at 650 nm were taken initially (t 0 ) and after time 4 hours (t 4 ) of incubation.
  • O.D. Optical density
  • the inhibition values can be plotted versus dosage for each active and the particular blend. This results in a dose response curve from which the dosage to yield 50% inhibition (1 50 ) can be calculated.
  • the 1 50 values are expressed as parts per million (ppm) of active material.
  • SI is less than 1, synergism exists; if SI is greater than 1, antagonism exists, if SI is equal to 1, an additive effect exists.
  • Example 1 deals with a blend of bis (Trichloromethyl) sulfone and o-phenylphenol.
  • This example shows the synergistic activity between o-phenylphenol and bis (Trichloromethyl) sulfone under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
  • Sulfone* & NaOPP @ pH 5.5 ppm ppm Synergy Sulfone NaOPP Ratio Sulfone:NaOPP Index 1.154 0.00 100:0 1.00 0.504 3.91 1.0:7.8 0.67 0.236 7.81 1.0:33.0 0.39 0.170 15.63 1.0:92.0 0.53 0.156 31.25 1.0:200.8 0.73 0.000 56.78 0:100 1.00
  • This example shows the synergistic activity between o-phenylphenol and 5-chloro-2-methyl-4-isothiazoline-3-one/2-methyl-4-isothiazoline-3-one under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
  • This example shows the synergistic activity between o-phenylphenol and tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
  • Pseudomonas sp. Escherchia coli
  • Enterobacter sp. Enterobacter sp.
  • Alcaligenes sp. Alcaligenes faecalis.
  • a sterile cotton swab to harvest some of the growth.
  • Place swab into a tube containing 10 mL sterile phosphate buffer Compare and adjust the turbidity of the organisms in the tube to 1 ⁇ 10 8 cfu/mL using a 0.5 MacFarland Turbidity Standard.
  • Row A through H Mixed Inoculum at a strength of 1X10E6 cfu/ml
  • microtiter plate Incubate the microtiter plate at the desired temperature for the desired amount of time. This plate represents the biostatic activity of the test compound(s). Bacterial plates are usually incubated at 35-37 C. for 24 hours.
  • the organism control (12 th column) and the nutrient broth control (11 th column) wells serve as controls for this experiment. If no growth appears in the organism control or if growth appears in the broth control, the test is invalid and must be repeated.
  • Layout of Combination Biocide Plate each level was replicated 8 times Biocide A (8X) Dazomet Biocide B (4X) OPP Well# Stock Sol 8000 ppm Stock Sol.
  • Biocide A (4X) Dazomet Well # Stock Sol. (4000 ppm) 1 1000 2 500 3 250 4 125 5 62.5 6 31.25 7 15.6 8 7.8 9 3.9 10 1.95 11 nutrient broth 12 organism control
  • MIC Minimum Inhibitory Concentration
  • K concentration ⁇ ⁇ of ⁇ ⁇ Biocide ⁇ ⁇ A ⁇ ⁇ in ⁇ ⁇ comb Concentration ⁇ ⁇ of ⁇ ⁇ Biocide ⁇ ⁇ A ⁇ ⁇ alone + concentration ⁇ ⁇ of ⁇ ⁇ Biocide ⁇ ⁇ B ⁇ ⁇ in ⁇ ⁇ comb concentration ⁇ ⁇ of ⁇ ⁇ Biocide ⁇ ⁇ B ⁇ ⁇ alone
  • o-phenylphenol we mean for it to include the sodium salt and/or mixtures of OPP with its sodium salt.
  • Cement admixtures includes but is not limited to lignosulfinates, sugars, organic polymers, and slurries such as calcium carbonate, kaolin, titanium dioxide.
  • from 8:1 to 1:8 includes any ratio within in that range such as 1:2, 1:3, 1:4, 1:5, 2:3, 2:4, 2:8, 7:1, 7:2, 5.2:1, or 1:5.2.
  • Antimicrobial includes any antimicrobial agents, biocides and preservatives. It can be any chemical that inhibit the growth of microorganisms. They are used depending on the products functions and the nature of the end use in the industrial sector. Antimicrobials will inhibit the growth of and or kill microorganisms in their applications, leading to sterile conditions. Antimicrobial agents consist of commodity chemicals as well as specialty chemicals and can be classified as oxidizing types and nonoxidizing types.
  • the performance of the antimicrobial is described as sterilant (kills all types of life forms completely), sproicidal (kills spores), disinfectant (kills all infectious bacteria), cidal (kills all organisms) and sanitizers (reduces the number of microorganisms to a safe level), antiseptic (prevents infections) and static (prevents growth of the microorganisms).
  • From 1:1 to 1:170 include any ratio that range for example 1:70 or 1:2.5.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Hydrology & Water Resources (AREA)
  • Engineering & Computer Science (AREA)
  • Environmental & Geological Engineering (AREA)
  • Water Supply & Treatment (AREA)
  • Organic Chemistry (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

Ortho phenylphenol acts synergistically with various other antimicrobial compounds commonly used in industrial applications.

Description

    RELATED APPLICATION
  • This application is a continuation of U.S. application Ser. No. 10/345,798, filed Jan. 16, 2003, which claims the benefit of U.S. Provisional Application No. 60/349,636 filed Jan. 17, 2002. Application Ser. Nos. 10/345,798 and 60/349,636 are incorporated by reference.
    • TECHNICAL FIELD
  • This invention relates to synergistic mixtures of o-phenylphenol and/or its sodium salt with tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione commonly used in cement admixtures and slurries.
    • BACKGROUND OF THE INVENTION
  • O-phenylphenol and Sodium orthophenylphenate (separately or collectively sometimes herein known as “OPP”, orthophenylphenol or o-phenylphenol) are used extensively as antimicrobial agents in various industrial applications such as preservation of various materials including paints, adhesives etc. as well as to control unwanted microorganisms found in various process waters such as cooling water, paper mills and petroleum production.
  • Microbiological growth can cause contamination of products that requires the use of preservatives, as well as process waters, where Antimicrobials are required to prevent contamination. Preservatives are required for a broad range of products including but not limited to adhesives, cosmetics and toiletries, disinfectants and sanitizers, leather, metalworking fluids, paints and coatings, plastics and resins, latex polymers, textiles and wood. Failure to preserve these products adequately will result in spoilage and loss of the materials to be preserved and will result in an economic loss. Similarly, microbiological growths can have dire consequences if process waters are not adequately treated. Process waters include but are not limited to: industrial recirculating water, paper products and paper, petroleum production and leather tanning. Process waters are of concern because when fouled with biofilms that develop from the indigenous microbes present, biofilms may develop into thick gelatinous like masses. Slime is produced by a wide range of bacteria, fungi, and yeast. Slime will interfere with the process resulting in a loss of heat transfer, corrosion and fouling. Slime also detracts from systems cleanliness.
    • SUMMARY OF THE INVENTION
  • This invention includes synergistic ratios of aqueous suspensions of orthophenylphenol or Sodium orthophenylphenate with the following chemical antimicrobials:
      • bis (Trichloromethyl) sulfone
      • 1-Bromo-3-chloro-5,5-dimethylhydantion
      • 1,2-Benzisothiazolin-3-one
      • bromonitrostyrene
      • 2,2-dibromo-3-nitrilopropionamide
      • 4,5-dicloro-1,2-dithiol-3-one
      • 5-chloro-2-methyl-4-isothiazoline-3-one/
      • 2-methyl-4-isothiazoline-3-one
      • Diiodomethyl-p-tolylsulfone
      • sodium hypochlorite
      • tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione
  • Generally, any ratio of OPP to the other antimicrobial within the range of 1%-99% to 99%-1% by weight may demonstrate a synergistic effect to some degree, but we prefer to use the most efficient combinations, which may include a wide range of ratios, as will be seen below.
    • DETAILED DESCRIPTION OF THE INVENTION:
  • Orthophenylphenol was found to produce synergistic blends with other antimicrobials. The synergistic blends were determined using a dose protocol. The actives were evaluated in synthetic white water with pH values of 5.5 and 8.0. The materials were tested against an artificial bacterial consortium containing approximately equal numbers of six bacterial strains. Although the test strains are representative of organisms present in paper mill systems, the effect is not limited to these bacteria. Two of the strains were Kiebsiella pneumoia (ATCC 13883) and Pseudomonas aeruginosa (ATCC 15442). The other four strains were isolated from papermill systems and have been identified as Curtobacterium flaccumfaciens, Burkhlderia cepacia, Bacillus maroccanus, and Pseudomonas glethei. Each strain was inoculated at 37° C. overnight, then suspended in sterile saline. Equal volumes of each strain were then combined to prepare the consortium. The bacterial consortium was distributed into the wells of a microtiter plate in the presence or absence of various concentrations of the active materials. The microtiter plates were incubated at 37° C. Optical density (O.D.) readings at 650 nm were taken initially (t0) and after time 4 hours (t4) of incubation.
  • The raw data was converted to “bacterial growth inhibition percentages” according to the following formula:
    % Inhibition=[(a−b)÷a]·100
  • where:
  • a=(O.D. of control at tn)−(O.D. of control at t0)
  • b=(O.D. of treatment at tn)−(O.D. of treatment at t0)
  • The inhibition values can be plotted versus dosage for each active and the particular blend. This results in a dose response curve from which the dosage to yield 50% inhibition (150) can be calculated. In the examples (tables) below, the 150 values are expressed as parts per million (ppm) of active material. The synergism index (SI) was calculated by the equations described by F. C. Kull, P. C. Eisman, H. D. Sylwestrowicz, and R. L. Mayer (1961), Applied Microbiology 9, 538-541. The values are based on the amount needed to achieve a specified end point. The end point selected for these studies was 50% inhibition of bacterial growth.
    Synergy Index (SI)=(QA÷Qa)+(QB÷Qb)
  • where:
  • QA=quantity of compound A in mixture, producing the end point
  • Qa=quantity of compound A1 acting alone, producing the end point
  • QB=quantity of compound B in mixture, producing the end point
  • Qb=quantity of compound B1 acting alone, producing the end point
  • If SI is less than 1, synergism exists; if SI is greater than 1, antagonism exists, if SI is equal to 1, an additive effect exists.
  • Example 1 deals with a blend of bis (Trichloromethyl) sulfone and o-phenylphenol.
    • EXAMPLE 1
  • This example shows the synergistic activity between o-phenylphenol and bis (Trichloromethyl) sulfone under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
    Sulfone* & NaOPP @ pH 5.5
    ppm ppm Synergy
    Sulfone NaOPP Ratio Sulfone:NaOPP Index
    1.154 0.00 100:0   1.00
    0.504 3.91 1.0:7.8  0.67
    0.236 7.81 1.0:33.0 0.39
    0.170 15.63 1.0:92.0 0.53
    0.156 31.25  1.0:200.8 0.73
    0.000 56.78  0:100 1.00
  • Sulfone* & NaOPP @ pH 8.0
    Ppm ppm Synergy
    Sulfone NaOPP Ratio Sulfone:NaOPP Index
    1.34 0.00 100:0   1.00
    0.77 3.91 1.0:5.0  0.67
    0.54 7.81 1.0:14.4 0.56
    0.45 15.63 1.0:34.5 0.61
    0.35 31.25 1.0:89.4 0.76
    0.05 62.50  1.0:1230.4 0.97
    0.00 67.8  0:100 1.00

    *Sulfone - Bis(trichlormethyl)sulfone
    • EXAMPLE 2
  • This example shows the synergistic activity between o-phenylphenol and 1-Bromo-3-chloro-5,5-dimethylhydantion under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
    BCDMH* & NaOPP @ pH 5.5
    ppm ppm Synergy
    BCDMH NaOPP Ratio BCDMH:NaOPP Index
    14.60 0.00 100:0  1.00
    9.10 3.91 1.0:0.4 0.67
    9.88 7.81 1.0:0.8 0.78
    10.98 15.63 1.0:1.4 0.95
    10.86 31.25 1.0:2.9 1.14
    6.25 67.52  1.0:10.8 1.29
    5.62 62.50  1.0:11.1 1.18
    3.13 82.87  1.0:26.5 1.27
    1.56 83.18  1.0:53.2 1.17
    0.78 80.42  1.0:102.9 1.08
    0.39 81.38  1.0:208.3 1.07
    0.20 76.21  1.0:390.2 0.99
    0.10 76.13  1.0:779.6 0.98
    0.00 78.40  0:100 1.00
  • BCDMH* & NaOPP @ pH 8.0
    ppm ppm Synergy
    BCDMH NaOPP Ratio BCDMH:NaOPP Index
    34.37 0.00 100:0  1.00
    11.51 3.91 1.0:0.3 0.37
    13.22 7.81 1.0:0.6 0.45
    15.92 15.63 1.0:1.0 0.58
    20.74 31.25 1.0:1.5 0.85
    20.94 62.50 1.0:3.0 1.09
    12.50 90.71 1.0:7.3 1.07
    6.25 116.26  1.0:18.6 1.08
    3.13 127.26  1.0:40.7 1.08
    1.56 136.91  1.0:87.6 1.10
    0.78 144.84  1.0:185.4 1.14
    0.39 137.29  1.0:351.5 1.07
    0.20 136.00  1.0:696.3 1.06
    0.10 131.07   1.0:1342.2 1.02
    3.13 127.26  0:100 1.00

    *BCDMH—1-Bromo-3-chloro-5,5-dimethylhydantoin
    • EXAMPLE 3
  • This example shows the synergistic activity between o-phenylphenol and 1,2-Benzisothiazolin-3-one under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
    BIT* & NaOPP @ pH 5.5
    ppm ppm Synergy
    BIT NaOPP Ratio BIT:NaOPP Index
    1.46 0.00 100:0    1.00
    1.14 3.91 1.0:3.4   0.83
    1.15 7.81 1.0:6.8   0.88
    1.15 15.63 1.0:13.6  0.97
    1.00 31.25 1.0:31.2  1.05
    0.63 53.37 1.0:85.4  1.06
    0.49 62.50 1.0:128.5  1.07
    0.31 73.11 1.0:233.9  1.07
    0.16 75.81 1.0:485.2  1.00
    0.08 78.91 1.0:1010.1 0.98
    0.04 75.98 1.0:1945.1 0.92
    0.02 81.73 1.0:4184.8 0.96
    0.01 82.29 1.0:8426.5 0.96
    0.00 84.96 0:100  1.00
  • BIT* & NaOPP @ pH 8.0
    ppm ppm Synergy
    BIT NaOPP Ratio BIT:NaOPP Index
    2.86 0.00 100:0  1.00
    2.77 3.91 1.0:1.4 1.01
    2.87 7.81 1.1:2.7 1.07
    2.88 15.63 1.0:5.4 1.14
    2.40 31.25  1.0:13.0 1.11
    2.28 62.50  1.0:27.4 1.34
    0.63 118.64  1.0:189.8 1.24
    0.31 117.62  1.0:376.4 1.12
    0.16 124.59  1.0:797.4 1.13
    0.08 121.17   1.0:1551.0 1.07
    0.04 118.13   1.0:3024.0 1.03
    0.02 120.98   1.0:6194.3 1.05
    0.01 117.97   1.0:12080.4 1.02
    0.00 116.41  0:100 1.00

    *BIT—1,2-Benzisothiazolin-3-one
    • EXAMPLE 4
  • This example shows the synergistic activity between o-phenylphenol and bromonitrostyrene under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
    BNS* & NaOPP @ pH 5.5
    ppm ppm Synergy
    BNS NaOPP Ratio BNS:NaOPP Index
    1.19 0.00 100:0    1.00
    1.14 3.91 1.0:3.4   1.01
    1.20 7.81 1.0:6.5   1.10
    1.04 15.63 1.0:15.0  1.05
    0.85 31.25 1.0:36.6  1.07
    0.63 45.57 1.0:72.9  1.03
    0.45 62.50 1.0:140.4  1.07
    0.31 73.45 1.0:235.0  1.08
    0.16 84.59 1.0:541.4  1.07
    0.08 89.51 1.0:1145.7 1.06
    0.04 91.28 1.0:2336.7 1.04
    0.02 92.98 1.0:4760.7 1.04
    0.00 90.47 0:100  1.00
  • BNS* & NaOPP @ pH 8.0
    ppm ppm Synergy
    BNS NaOPP Ratio BNS:NaOPP Index
    3.08 0.00 100:0   1.00
    3.19 3.91 1.0:1.2  1.07
    2.83 7.81 1.0:2.8  0.98
    2.90 15.63 1.0:5.4  1.07
    2.96 31.25 1.0:10.6 1.21
    2.50 39.46 1.0:15.8 1.13
    2.00 62.50 1.0:31.2 1.16
    1.25 86.33 1.0:69.1 1.11
    0.63 107.36  1.0:171.8 1.07
    0.31 124.73  1.0:399.1 1.11
    0.16 128.83  1.0:824.5 1.10
    0.08 131.28  1.0:1680.4 1.09
    0.04 120.73  1.0:3090.6 0.99
    0.02 115.35  1.0:5905.9 0.94
    0.00 123.16  0:100 1.00

    *BNS—Bromonitrostyrene
    • EXAMPLE 5
  • This example shows the synergistic activity between o-phenylphenol and 2,2-dibromo-3-nitrilopropionamide under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
    DBNPA & NaOPP @ pH 5.5
    ppm ppm Synergy
    DBNPA NaOPP Ratio DBNPA:NaOPP Index
    1.69 0.00 100:0  1.00
    1.71 0.49 1.0:0.3 1.02
    1.68 0.98 1.0:0.6 1.00
    1.72 1.95 1.0:1.1 1.04
    1.71 3.91 1.0:2.3 1.06
    1.58 7.81 1.0:4.9 1.02
    1.54 15.63  1.0:10.1 1.09
    1.44 31.25  1.0:21.7 1.20
    1.25 62.03  1.0:49.6 1.44
    1.21 62.50  1.0:51.6 1.42
    0.63 84.50  1.0:135.2 1.33
    0.31 88.90  1.0:284.5 1.19
    0.16 95.11  1.0:608.7 1.17
    0.08 97.67   1.0:1250.1 1.15
    0.00 88.38  0:100 1.00
  • DBNPA & NaOPP @ pH 8.0
    ppm ppm Synergy
    DBNPA NaOPP Ratio DBNPA:NaOPP Index
    3.01 0.00 100:0  1.00
    2.88 0.49 1.0:0.2 0.96
    2.73 0.98 1.0:0.4 0.91
    2.82 1.95 1.0:0.7 0.95
    2.94 3.91 1.0:1.3 1.00
    2.80 7.81 1.0:2.8 0.99
    2.81 15.63 1.0:5.6 1.05
    2.72 31.25  1.0:11.5 1.13
    2.50 55.48  1.0:22.2 1.23
    2.54 62.50  1.0:24.6 1.30
    1.25 121.24  1.0:97.0 1.30
    0.63 126.72  1.0:202.7 1.13
    0.31 121.38  1.0:388.4 0.99
    0.16 140.84  1.0:901.4 1.08
    0.08 109.38   1.0:1400.1 0.82
    0.00 137.13  0:100 1.00

    *DBNPA—2,2-Dibromo-3-nitrilopropionamide
    • EXAMPLE 6
  • This example shows the synergistic activity between o-phenylphenol and 4,5-dicloro-1,2-dithiol-3-one under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
    Dithiol & NaOPP @ pH 5.5
    ppm ppm Ratio Synergy
    Dithiol NaOPP Dithiol:NaOPP Index
    0.073 0.00 100:0   1.00
    0.070 0.49 1.0:6.9  0.97
    0.074 0.98 1.0:13.2  1.03
    0.091 1.95 1.0:21.5  1.26
    0.079 3.91 1.0:49.2  1.12
    0.073 7.81 1.0:107.5 1.06
    0.069 15.63 1.0:227.1 1.08
    0.061 31.25 1.0:514.7 1.10
    0.058 62.50  1.0:1080.9 1.32
    0.039 75.14  1.0:1923.7 1.17
    0.000 0.07 0:100 1.00
  • Dithiol & NaOPP @ pH 8.0
    ppm ppm Synergy
    Dithiol NaOPP Ratio Dithiol:NaOPP Index
    0.16 0.00 100:0   1.00
    0.16 0.49 1.0:3.0  1.00
    0.16 0.98 1.0:6.0  1.01
    0.17 1.95 1.0:11.6 1.05
    0.17 3.91 1.0:22.6 1.09
    0.17 7.81 1.0:46.3 1.10
    0.16 15.63 1.0:95.5 1.13
    0.17 31.25  1.0:183.6 1.28
    0.20 62.50  1.0:320.3 1.67
    0.08 138.33  1.0:1770.6 1.52
    0.04 137.46  1.0:3519.0 1.28
    0.00 132.71  0:100 1.00

    * Dithiol - 4,5-Dichloro-1,2-dithiol-3-one
    • EXAMPLE 7
  • This example shows the synergistic activity between o-phenylphenol and 5-chloro-2-methyl-4-isothiazoline-3-one/2-methyl-4-isothiazoline-3-one under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
    Iso* & NaOPP @ pH 5.5
    ppm ppm % Synergy
    Iso NaOPP Ratio Iso:NaOPP Inhibition Index
    0.09 0.00 100:0   50 1.00
    0.09 3.91 1.0:41.4  50 1.10
    0.08 7.81 1.0:93.1  50 1.03
    0.07 15.63 1.0:219.8 50 0.98
    0.06 29.35 1.0:469.5 50 1.05
    0.06 31.25 1.0:549.3 50 1.01
    0.03 51.17  1.0:1637.4 50 0.97
    0.02 62.50  1.0:2649.1 50 1.02
    0.02 71.02  1.0:4545.4 50 1.03
    0.01 72.33  1.0:9258.8 50 0.96
    0.00 71.54  1.0:18313.3 50 0.91
    0.00 76.93  1.0:39390.6 50 0.95
    0.00 82.73 0:100 50 1.00
  • Iso* & NaOPP @ pH 8.0
    ppm ppm % Synergy
    Iso NaOPP Ratio Iso:NaOPP Inhibition Index
    0.09 0.00 100:0   50 1.00
    0.09 3.91 1.0:41.4  50 1.13
    0.09 7.81 1.1:86.4  50 1.12
    0.08 15.63 1.0:191.7 50 1.09
    0.08 31.25 1.0:381.2 50 1.23
    0.06 53.65 1.0:858.4 50 1.20
    0.07 62.50 1.0:955.8 50 1.31
    0.03 93.37  1.0:2987.9 50 1.21
    0.02 116.98  1.0:7486.9 50 1.09
    0.01 114.13  1.0:14609.0 50 1.09
    0.00 119.07  1.0:30481.2 50 1.09
    0.00 114.29  1.0:58514.5 50 1.02
    0.00 114.14 0:100 50 1.00

    *Iso - Mixture of 5-Chloro-2-methyl-4-isothiazolin-3-one and 2-Methyl-4-isothiazolin-3-one
    • EXAMPLE 8
  • This example shows the synergistic activity between o-phenylphenol and Diiodomethyl-p-tolylsulfone under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
    DIMTS* & NaOPP @ pH 5.5
    ppm ppm Synergy
    DIMTS NaOPP Ratio DIMTS:NaOPP Index
    31.65 0.00 100:0   1.00
    25.82 3.91 1.0:0.15 0.86
    46.44 7.81 1.0:0.17 1.56
    36.85 15.63 1.0:0.4  1.35
    34.20 31.25 1.0:0.9  1.45
    25.00 35.97 1.0:1.4  1.22
    12.50 58.85 1.0:4.7  1.10
    6.33 62.50 1.0:9.9  0.94
    6.25 64.52 1.0:10.3 0.97
    3.13 77.03 1.0:24.6 1.02
    1.56 87.63 1.0:56.1 1.09
    0.78 90.32  1.0:115.6 1.10
    0.39 80.40  1.0:205.8 0.97
    0.20 77.72  1.0:397.9 0.93
    0.10 82.24  1.0:842.2 0.98
    0.00 84.10  0:100 1.00
  • DIMTS* & NaOPP @ pH 8.0
    ppm ppm Synergy
    DIMTS NaOPP Ratio DIMTS:NaOPP Index**
    22.84 0.00 100:0  1.00
    33.78 3.91 1.0:0.1 1.52
    31.04 7.81 1.0:0.3 1.44
    28.66 15.63 1.0:0.5 1.42
    25.20 31.25 1.0:1.2 142
    14.75 62.50 1.0:4.2 1.29
    6.25 63.44  1.0:10.2 0.92
    3.13 71.82  1.0:23.0 0.87
    1.56 93.40  1.0:59.8 1.02
    0.78 96.85  1.0:124.0 1.02
    0.39 104.09  1.0:266.5 1.08
    0.20 94.29  1.0:482.8 0.97
    0.10 99.53   1.0:1019.2 1.02
    0.00 97.74  0:100 1.00

    *DIMTS - Diiodomethyl-p-tolylsulfone

    **synergy Index Values Calculated Using 40% Inhibition of Bacterial Growth
    • EXAMPLE 9
  • This example shows the synergistic activity between o-phenylphenol and sodium hypochlorite under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
    NaOCl* & NaOPP @ pH 5.5
    ppm ppm Synergy
    NaOCl NaOPP Ratio NaOCl:NaOPP Index**
    55.27 0.00 100:0   1.00
    22.93 3.91 1.0:0.17 0.49
    31.92 7.81 1.0:0.24 0.72
    31.73 15.63 1.0:0.49 0.86
    35.57 31.25 1.0:0.88 1.21
    25.00 43.82 1.0:1.8  1.25
    12.50 56.87 1.0:4.5  1.26
    6.25 57.65 1.0:9.2  1.16
    3.13 65.39 1.0:20.9 1.25
    1.56 61.92 1.0:39.6 1.16
    0.78 61.29 1.0:78.5 1.13
    0.39 53.86  1.0:137.9 0.99
    0.20 48.05  1.0:246.0 0.88
    0.10 47.55  1.0:486.9 087
    0.00 54.92  0:100 1.00

    *NaOCl - Sodium Hypochlorite

    **Synergy Index Values Calculated Using 30% Inhibition of Bacterial Growth
    • EXAMPLE 10
  • This example shows the synergistic activity between o-phenylphenol and tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione under a concurrent feed strategy, against article bacterial consortium in synthetic white water at pH 5.5 and 8.0.
    Dazomet* & NaOPP @ pH 5.5
    ppm ppm Ratio Synergy
    Dazomet NaOPP Dazomet:NaOPP Index
    6.176 0.00 100:0   1.00
    3.848 3.91 1.0:1.0  0.66
    1.089 7.81 1.0:7.2  0.25
    1.119 15.63 1.0:14.0 0.33
    0.366 31.25 1.0:85.4 0.36
    0.368 62.50  1.0:170.0 0.66
    0.000 56.78  0:100 1.00
  • Dazomet* & NaOPP @ pH 8.0
    Ppm ppm Ratio Synergy
    Dazomet NaOPP Dazomet:NaOPP Index
    5.34 0.00 100:0  1.00
    5.66 3.91 1.0:0.7 1.09
    4.97 7.81 1.0:1.6 0.98
    4.70 15.63 1.0:3.3 0.98
    4.59 31.25 1.0:6.8 1.06
    4.51 62.50  1.0:13.9 1.24
    2.43 125.0  1.0:51.5 1.24
    0.00 158.32  0:100 1.00

    *Dazomet - tetrahydo-3,5-dimethyl-2H-1-3-5-thiadiazine-2-thione
  • An additional example of the synergism of Dazomet and NaOPP can be seen as follows.
  • EQUIPMENT used for the experiment are as follows:
      • 1. Incubator capable of maintaining a variable temperature range (25-45 C.);
      • 2. Samples of each biocide or test compound to be examined;
      • 3. Microtiter plates—96 well with lid, sterile;
      • 4. 8-12 channel micropipetting device capable of pipetting 0-250 ul volumes;
      • 5. Micropipette tips capable of holding up to 250 ul volumes;
      • 6. Sterile microbiological culture broth. Trypticase Soy Broth (TSB) or Nutrient Broth (NB) is recommended for bacteria and Sabouraud Maltose Broth (SMB) or Sabouraud Dextrose Broth (SDB) is recommended for yeasts and molds. In the case of this particular study the microbiological culture medium was Nutrient Broth at pH 7.0, 8.0 and 9.0;
      • 7. Pure cultures of microorganisms of choice grown on appropriate agar medium;
      • 8. Sterile distilled water;
      • 9. 100 mL volumetric flasks (one for each biocide to be tested);
      • 10. Sterile 10 mL tubes of Phosphate buffer (Butterfield's buffer pH 7.2+/−0.2). Contains purified water, monobasic potassium phosphate and sodium hydroxide for pH adjustment;
      • 11. Sterile cotton swabs;
      • 12. 0.5 MacFarland Turbidity Standard;
  • Preparation of Bacterial Inocula
  • The day before testing, perform a streak plate of each organism to be tested on an appropriate agar medium (Trypticase Soy Agar). Organisms tested in this study were.
  • Wild strain bacteria isolated from previously contaminated industrial systems and which were identified as: Pseudomonas sp., Escherchia coli, Enterobacter sp., Alcaligenes sp. and Alcaligenes faecalis. On the day of the test, use a sterile cotton swab to harvest some of the growth. Place swab into a tube containing 10 mL sterile phosphate buffer. Compare and adjust the turbidity of the organisms in the tube to 1×108 cfu/mL using a 0.5 MacFarland Turbidity Standard. Dilute the 10 mL tube into 90 mL of sterile 2× nutrient broth at pH 7.0, 8.0 and 9.0.
  • The following procedure was used:
      • 1. Design the layout of the microtiter plates based on the number of organisms to test and the number of biocides and desired concentrations to test. A separate microtiter plate is required for testing each biocide alone, in addition to the combination microtiter plate.
      • 2. Prepare a working stock solution of each biocide to be tested. For the combination microtiter plate, the working stock solution of Biocide A will be 8× the concentration desired in the first well of the combination microtiter plate. The working stock solution of Biocide B will be 4× the concentration desired in the first well of the combination microtiter plate. For the alone microtiter plates, the working stock solutions of Biocide A and Biocide B will both be 4× the concentration desired in the first well of the single biocide microtiter plates.
  • Biocide A
  • Tetrahydro-3-5-dimethyl-2H-1,3-5-thiadiazine-2-thione (Dazomet): (For combination plates) A solution of this product, which is 99% active, was made as follows: 8×8000=8000 ppm active=8000/0.99=8080 ppm, 0.8 g into 100 mL MeOH and sterile diH2O.
  • Levels to test are:
  • 1000 ppm, 500 ppm, 250 ppm, 125 ppm, 62.5 ppm, 31.2 ppm, 15.6 ppm, 7.8 ppm, 3.9 ppm, 1.95 ppm
  • (For alone plates) A solution was made as follows: 4×4000=16000 ppm active=16000/0.99=16161 pm, 1.6 g into 100 mL MeOH and sterile diH2O. Levels to test are: 4000 ppm, 2000 ppm, 1000 ppm, 500 ppm, 250 ppm, 125 ppm, 62.5 ppm, 31.2 ppm, 15.6 ppm, 7.8 ppm, 3.9 ppm, 1.95 ppm.
  • Biocide B
  • o-Phenylphenol (OPP): (For combination plates) Make a solution of this product which is 99% active, 4×125=500 ppm active=500/0.99=505 ppm, 0.05 g into 100 mL MeOH and sterile diH2O. Level to test is 125 ppm.
  • (For alone plates) A solution was made as follows: 4×4000=16000 ppm active=16000/0.99=16161 ppm, 1.6 into 100 mL MeOH and sterile diH2O. Levels to test are: 4000 ppm, 2000 ppm, 1000 ppm, 500 ppm, 250 ppm, 125 ppm, 62.5 ppm, 31.2 ppm, 15.6 ppm, 7.8 ppm, 3.9 ppm, 1.95 ppm
      • 3. Place 50 ul of sterile distilled water in all of the rows in columns 1 through 10, and 100 ul of sterile distilled water in all of the rows in columns 11 and 12 of the 96 well combination microtiter plate. Place 100 ul of sterile distilled water in each well of the 96 well alone microtiter plates.
      • 4. For the combination microtiter plate, place 50 ul of the Biocide A stock solution into all of the rows in column 1 of the combination microtiter plate.
      • 5. Serially dilute Biocide A twofold across the microtiter plate through column 10. Mix each well by pipetting up and down as you are performing the dilution scheme.
      • 6. Place 50 ul of the Biocide B stock solution into all the rows in columns I through 10 of the combination microtiter plate.
      • 7. For the single biocide microtiter plates, place 100 ul of Biocide A (4× working stock solution) into all rows in the column. Serially dilute Biocide A two fold across the microtiter plate through column 10. Mix each well by pipetting up and down as you are performing the dilution 5 scheme.
      • 8. Repeat Step 7 for the Biocide B microtiter plate.
      • 9. The 11th column in all plates serves as a broth control. Add 100 ul of 2× nutrient broth at either pH 7.0, 8.0 or 9.0 into each well in this column.
      • 10. The 11th column serves as an organism control.
      • 11. Add 100 ul of the inoculum to the appropriate rows of the microtiter plate in columns 1 through 10 and 12 as listed below.
  • Bacterial Plates
  • Row A through H: Mixed Inoculum at a strength of 1X10E6 cfu/ml
  • Incubate the microtiter plate at the desired temperature for the desired amount of time. This plate represents the biostatic activity of the test compound(s). Bacterial plates are usually incubated at 35-37 C. for 24 hours.
  • Quality Control
  • The organism control (12th column) and the nutrient broth control (11th column) wells serve as controls for this experiment. If no growth appears in the organism control or if growth appears in the broth control, the test is invalid and must be repeated.
    Layout of Combination Biocide Plate each level was replicated 8 times
    Biocide A (8X)
    Dazomet Biocide B (4X) OPP
    Well# Stock Sol 8000 ppm Stock Sol. 500 ppm Ratio A:B
    1 1000 125 8:1
    2 500 125 4:1
    3 250 125 2:1
    4 125 125 1:1
    5 62.5 125 1:2
    6 31.25 125 1:4
    7 15.6 125 1:8
    8 7.8 125  1:16
    9 3.9 125  1:30
    10 1.95 125  1:65
    11 nutrient broth nutrient broth
    12 organism control organism control
  • Layout of Alone Biocide Plate the levels were replicated 8 times:
    Biocide A (4X) Dazomet
    Well # Stock Sol. (4000 ppm)
    1 1000
    2 500
    3 250
    4 125
    5 62.5
    6 31.25
    7 15.6
    8 7.8
    9 3.9
    10 1.95
    11 nutrient broth
    12 organism control
  • Layout of Alone Biocide Plate #2 the levels were replicated 8 times:
    Well #
    Biocide A (4X) Dazomet
    Stock Sol. (16000 ppm)
    1 4000
    2 2000
    3 1000
    4 nutrient broth
    5 organism control
    Biocide B (4X) OPP
    Stock Sol. (4000 ppm)
    1 1000
    2 500
    3 250
    4 125
    5 62.5
    6 31.25
    7 15.6
    8 7.8
    9 3.9
    10 1.95
    11 nutrient broth
    12 organism control
  • Layout of Alone Biocide Plate #2 the levels were replicated 8 times:
    Biocide A (4X) OPP
    Well # Stock Sol. (16000 ppm)
    1 4000
    2 2000
    3 1000
    4 nutrient broth
    5 organism control
  • Interpretation
  • Minimum Inhibitory Concentration (MIC)—the lowest concentration of test compound that results in no evidence of growth at the end of the incubation period.
  • Determine the K value for each combination biocide the MIC level: K = concentration ⁢   ⁢ of ⁢   ⁢ Biocide ⁢   ⁢ A ⁢   ⁢ in ⁢   ⁢ comb Concentration ⁢   ⁢ of ⁢   ⁢ Biocide ⁢   ⁢ A ⁢   ⁢ alone + concentration ⁢   ⁢ of ⁢   ⁢ Biocide ⁢   ⁢ B ⁢   ⁢ in ⁢   ⁢ comb concentration ⁢   ⁢ of ⁢   ⁢ Biocide ⁢   ⁢ B ⁢   ⁢ alone
  • If K<1, the biocides are considered to be synergistic.
  • If K=1, the biocides are considered to be additive
  • If K>1, the biocides are considered to be antagonistic.
  • Results of Bacterial Testing
    MIC RESULTS against
    mixed inoculum of
    bacteria
    Biocide pH PPM
    Dazomet 7.0 2000
    Dazomet 8.0 2000
    Dazomet 9.0 4000
    OPP 7.0 2000
    OPP 8.0 1000
    OPP 9.0 500
  • Dazomet* &
    NaOPP @ pH 7.0
    ppm ppm Ratio Synergy
    Dazomet NaOPP Dazomet:NaOPP Index
    1000 125 8:1 0.5625
    500 125 4:1 0.3125
    250 125 2:1 0.1875
    125 125 1:1 0.1250
    62.5 125 1:2 0.0938
    31.25 125 1:4 0.0781
    15.6 125 1:8 0.0700
  • Dazomet* &
    NaOPP @ pH 8.0
    ppm ppm Ratio Synergy
    Dazomet NaOPP Dazomet:NaOPP Index
    1000 125 8:1 0.6250
    500 125 4:1 0.3750
    250 125 2:1 0.2500
    125 125 1:1 0.1875
    62.5 125 1:2 0.1562
  • Dazomet* &
    NaOPP @ pH 9.0
    ppm ppm Ratio Synergy
    Dazomet NaOPP Dazomet:NaOPP Index
    1000 125 8:1 0.5
    500 125 4:1 0.375

    *Dazomet - tetrahydo-3,5-dimethyl-2H-1-3-5-thiadiazine-2-thione
  • In the claims below, where we use the term o-phenylphenol we mean for it to include the sodium salt and/or mixtures of OPP with its sodium salt.
  • Cement admixtures includes but is not limited to lignosulfinates, sugars, organic polymers, and slurries such as calcium carbonate, kaolin, titanium dioxide.
  • from 8:1 to 1:8 includes any ratio within in that range such as 1:2, 1:3, 1:4, 1:5, 2:3, 2:4, 2:8, 7:1, 7:2, 5.2:1, or 1:5.2.
  • Antimicrobial includes any antimicrobial agents, biocides and preservatives. It can be any chemical that inhibit the growth of microorganisms. They are used depending on the products functions and the nature of the end use in the industrial sector. Antimicrobials will inhibit the growth of and or kill microorganisms in their applications, leading to sterile conditions. Antimicrobial agents consist of commodity chemicals as well as specialty chemicals and can be classified as oxidizing types and nonoxidizing types. In these categories, the performance of the antimicrobial is described as sterilant (kills all types of life forms completely), sproicidal (kills spores), disinfectant (kills all infectious bacteria), cidal (kills all organisms) and sanitizers (reduces the number of microorganisms to a safe level), antiseptic (prevents infections) and static (prevents growth of the microorganisms).
  • From 1:1 to 1:170 include any ratio that range for example 1:70 or 1:2.5.

Claims (12)

1. An antimicrobial synergistic mixture of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione and o-phenylphenol wherein the mixture is determined to be antimicrobial synergistic by having a synergistic index of less than 1.
2. An antimicrobial synergistic mixture as recited in claim 1 wherein the ratio of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione to o-phenylphenol is from 8:1 to 1:8.
3. An antimicrobial synergistic mixture as recited in claim 1 wherein at around a pH of 5.5 the ratio of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione to o-phenylphenol is from 1:1 to 1:170.
4. An antimicrobial synergistic mixture as recited in claim 1 wherein at around a pH of 7.0 the ratio of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione to o-phenylphenol is from 8:1 to 1:8.
5. An antimicrobial synergistic mixture as recited in claim 1 wherein at around a pH of 8.0 the ratio of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione to o-phenylphenol is from 8:1 to 1:2.
6. An antimicrobial synergistic mixture as recited in claim 1 wherein at around a pH of 8.0 the ratio of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione to o-phenylphenol is around 4:1.
7. A method of controlling antimicrobials in cement admixtures and slurries comprising:
a. providing a cement admixture; and
b. adding an antimicrobial synergistic mixture of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione and o-phenylphenol wherein the mixture is determined to be antimicrobial synergistic by having a synergistic index of less than 1
8. A method as recited in claim 7 wherein the ratio of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione to o-phenylphenol is from 8:1 to 1:8.
9. A method as recited in claim 7 wherein at around a pH of 5.5 the ratio of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione to o-phenylphenol is from 1:1 to 1:170.
10. A method as recited in claim 7 wherein at around a pH of 7.0 the ratio of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione to o-phenylphenol is from 8:1 to 1:8.
11. A method as recited as recited in claim 7 wherein at around a pH of 8.0 the ratio of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione to o-phenylphenol is from 8:1 to 1:2.
12. A method as recited in claim 7 wherein at around a pH of 8.0 the ratio of tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione to o-phenylphenol is around 4:1.
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US8957129B2 (en) 2012-05-07 2015-02-17 Rhodia Operations Aqueous coatings and paints incorporating one or more antimicrobial biosurfactants and methods for using same
EP3006505A1 (en) 2012-05-07 2016-04-13 Rhodia Operations Aqueous coatings and paints incorporating one or more antimicrobial biosurfactants and methods for using same
WO2016196116A1 (en) * 2015-05-31 2016-12-08 Dow Global Technologies Llc Microbicidal composition containing ortophenylphenol and isothiazolinone
CN107979974A (en) * 2015-05-31 2018-05-01 陶氏环球技术有限责任公司 Microbicide compositions containing o-phenylphenol and isothiazolinones
JP2018516251A (en) * 2015-05-31 2018-06-21 ダウ グローバル テクノロジーズ エルエルシー Bactericidal composition containing orthophenylphenol and isothiazolinone
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AU2003210557A1 (en) 2003-09-02
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US7262222B2 (en) 2007-08-28

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