U.S. patent application number 11/677618 was filed with the patent office on 2007-08-30 for synergistic mixtures of o-phenylphenol and dazomet.
Invention is credited to Paul E. Carlson, Jodi L. Martin, H. Edwin Nehus.
Application Number | 20070203126 11/677618 |
Document ID | / |
Family ID | 27613303 |
Filed Date | 2007-08-30 |
United States Patent
Application |
20070203126 |
Kind Code |
A1 |
Carlson; Paul E. ; et
al. |
August 30, 2007 |
Synergistic Mixtures of O-Phenylphenol and Dazomet
Abstract
Ortho phenylphenol acts synergistically with various other
antimicrobial compounds commonly used in industrial
applications.
Inventors: |
Carlson; Paul E.;
(Pittsburgh, PA) ; Nehus; H. Edwin; (Pittsburgh,
PA) ; Martin; Jodi L.; (Imperial, PA) |
Correspondence
Address: |
Beck & Thomas, P.C.;SUITE 100
1575 McFARLAND ROAD
PITTSBURGH
PA
15216-1808
US
|
Family ID: |
27613303 |
Appl. No.: |
11/677618 |
Filed: |
February 22, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10345798 |
Jan 16, 2003 |
|
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11677618 |
Feb 22, 2007 |
|
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60349636 |
Jan 17, 2002 |
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Current U.S.
Class: |
514/223.8 |
Current CPC
Class: |
A61K 31/05 20130101;
A61K 31/155 20130101; A61K 31/41 20130101; A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 2300/00 20130101; A61K 2300/00 20130101; C02F
2103/023 20130101; A61K 31/53 20130101; A61K 31/41 20130101; A61K
31/155 20130101; A61K 31/17 20130101; A61K 31/045 20130101; A61K
31/53 20130101; A61K 31/05 20130101; A61K 31/17 20130101; C02F 1/50
20130101; A61K 31/045 20130101 |
Class at
Publication: |
514/223.8 |
International
Class: |
C04B 16/00 20060101
C04B016/00; A61K 31/54 20060101 A61K031/54 |
Claims
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.
Description
RELATED APPLICATION
[0001] 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
[0002] 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
[0003] 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.
[0004] 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
[0005] This invention includes synergistic ratios of aqueous
suspensions of orthophenylphenol or Sodium orthophenylphenate with
the following chemical antimicrobials: [0006] bis (Trichloromethyl)
sulfone [0007] 1-Bromo-3-chloro-5,5-dimethylhydantion [0008]
1,2-Benzisothiazolin-3-one [0009] bromonitrostyrene [0010]
2,2-dibromo-3-nitrilopropionamide [0011]
4,5-dicloro-1,2-dithiol-3-one [0012]
5-chloro-2-methyl-4-isothiazoline-3-one/ [0013]
2-methyl-4-isothiazoline-3-one [0014] Diiodomethyl-p-tolylsulfone
[0015] sodium hypochlorite [0016]
tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione
[0017] 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:
[0018] 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.degree. 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.degree. C.
Optical density (O.D.) readings at 650 nm were taken initially
(t.sub.0) and after time 4 hours (t.sub.4) of incubation.
[0019] The raw data was converted to "bacterial growth inhibition
percentages" according to the following formula: %
Inhibition=[(a-b)/a]100
[0020] where:
[0021] a=(O.D. of control at t.sub.n)-(O.D. of control at
t.sub.0)
[0022] b=(O.D. of treatment at t.sub.n)-(O.D. of treatment at
t.sub.0)
[0023] 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.sub.50) can
be calculated. In the examples (tables) below, the 1.sub.50 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)
[0024] where:
[0025] QA=quantity of compound A in mixture, producing the end
point
[0026] Qa=quantity of compound A.sub.1 acting alone, producing the
end point
[0027] QB=quantity of compound B in mixture, producing the end
point
[0028] Qb=quantity of compound B.sub.1 acting alone, producing the
end point
[0029] 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.
[0030] Example 1 deals with a blend of bis (Trichloromethyl)
sulfone and o-phenylphenol.
EXAMPLE 1
[0031] 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. TABLE-US-00001 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
[0032] TABLE-US-00002 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
[0033] 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. TABLE-US-00003 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
[0034] TABLE-US-00004 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
[0035] 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. TABLE-US-00005 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
[0036] TABLE-US-00006 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
[0037] 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. TABLE-US-00007 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
[0038] TABLE-US-00008 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
[0039] 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. TABLE-US-00009 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
[0040] TABLE-US-00010 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
[0041] 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. TABLE-US-00011 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
[0042] TABLE-US-00012 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
[0043] This example shows the synergistic activity between
o-phenylphenol and
5-chloro-2-methyl-4-isothiazoline-3-one/2-methyl-4-isothiazoline-3-on-
e under a concurrent feed strategy, against article bacterial
consortium in synthetic white water at pH 5.5 and 8.0.
TABLE-US-00013 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
[0044] TABLE-US-00014 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
[0045] 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. TABLE-US-00015 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
[0046] TABLE-US-00016 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
[0047] 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. TABLE-US-00017 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
[0048] 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. TABLE-US-00018 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
[0049] TABLE-US-00019 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
[0050] An additional example of the synergism of Dazomet and NaOPP
can be seen as follows.
[0051] EQUIPMENT used for the experiment are as follows: [0052] 1.
Incubator capable of maintaining a variable temperature range
(25-45 C.); [0053] 2. Samples of each biocide or test compound to
be examined; [0054] 3. Microtiter plates--96 well with lid,
sterile; [0055] 4. 8-12 channel micropipetting device capable of
pipetting 0-250 ul volumes; [0056] 5. Micropipette tips capable of
holding up to 250 ul volumes; [0057] 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; [0058] 7. Pure
cultures of microorganisms of choice grown on appropriate agar
medium; [0059] 8. Sterile distilled water; [0060] 9. 100 mL
volumetric flasks (one for each biocide to be tested); [0061] 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; [0062] 11. Sterile cotton
swabs; [0063] 12. 0.5 MacFarland Turbidity Standard;
[0064] Preparation of Bacterial Inocula
[0065] 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.
[0066] 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.times.10.sup.8 cfu/mL using a 0.5
MacFarland Turbidity Standard. Dilute the 10 mL tube into 90 mL of
sterile 2.times. nutrient broth at pH 7.0, 8.0 and 9.0.
[0067] The following procedure was used: [0068] 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. [0069] 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.times. the concentration desired in the first
well of the combination microtiter plate. The working stock
solution of Biocide B will be 4.times. 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.times. the concentration desired in the
first well of the single biocide microtiter plates.
[0070] Biocide A
[0071] 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.times.8000=8000 ppm
active=8000/0.99=8080 ppm, 0.8 g into 100 mL MeOH and sterile
diH.sub.2O.
[0072] Levels to test are:
[0073] 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
[0074] (For alone plates) A solution was made as follows:
4.times.4000=16000 ppm active=16000/0.99=16161 pm, 1.6 g into 100
mL MeOH and sterile diH.sub.2O. 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.
[0075] Biocide B
[0076] o-Phenylphenol (OPP): (For combination plates) Make a
solution of this product which is 99% active, 4.times.125=500 ppm
active=500/0.99=505 ppm, 0.05 g into 100 mL MeOH and sterile
diH.sub.2O. Level to test is 125 ppm.
[0077] (For alone plates) A solution was made as follows:
4.times.4000=16000 ppm active=16000/0.99=16161 ppm, 1.6 into 100 mL
MeOH and sterile diH.sub.2O. 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 [0078] 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. [0079] 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. [0080] 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. [0081] 6. Place 50 ul of the Biocide B stock
solution into all the rows in columns I through 10 of the
combination microtiter plate. [0082] 7. For the single biocide
microtiter plates, place 100 ul of Biocide A (4.times. 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. [0083] 8. Repeat Step 7 for the Biocide B
microtiter plate. [0084] 9. The 11.sup.th column in all plates
serves as a broth control. Add 100 ul of 2.times. nutrient broth at
either pH 7.0, 8.0 or 9.0 into each well in this column. [0085] 10.
The 11.sup.th column serves as an organism control. [0086] 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.
[0087] Bacterial Plates
[0088] Row A through H: Mixed Inoculum at a strength of 1X10E6
cfu/ml
[0089] 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.
[0090] Quality Control
[0091] The organism control (12.sup.th column) and the nutrient
broth control (11.sup.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. TABLE-US-00020 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
[0092] TABLE-US-00021 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
[0093] TABLE-US-00022 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
[0094] TABLE-US-00023 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
[0095] Interpretation
[0096] Minimum Inhibitory Concentration (MIC)--the lowest
concentration of test compound that results in no evidence of
growth at the end of the incubation period.
[0097] Determine the K value for each combination biocide the MIC
level: K = concentration .times. .times. of .times. .times. Biocide
.times. .times. A .times. .times. in .times. .times. comb
Concentration .times. .times. of .times. .times. Biocide .times.
.times. A .times. .times. alone + concentration .times. .times. of
.times. .times. Biocide .times. .times. B .times. .times. in
.times. .times. comb concentration .times. .times. of .times.
.times. Biocide .times. .times. B .times. .times. alone
##EQU1##
[0098] If K<1, the biocides are considered to be
synergistic.
[0099] If K=1, the biocides are considered to be additive
[0100] If K>1, the biocides are considered to be
antagonistic.
[0101] Results of Bacterial Testing TABLE-US-00024 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
[0102] TABLE-US-00025 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
[0103] TABLE-US-00026 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
[0104] TABLE-US-00027 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
[0105] 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.
[0106] Cement admixtures includes but is not limited to
lignosulfinates, sugars, organic polymers, and slurries such as
calcium carbonate, kaolin, titanium dioxide.
[0107] 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.
[0108] 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).
[0109] From 1:1 to 1:170 include any ratio that range for example
1:70 or 1:2.5.
* * * * *