MICROBICIDAL COMPOSITION

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Information

Patent Application
20160219882

References
Source

Publication Number
20160219882
Date Filed
October 03, 2014
9 years ago
Date Published
August 04, 2016
7 years ago

Inventors
Original Assignees
- DowDuPont Inc.
- ROHM & HAAS COMPANY

CPC
International Classifications
- A01N43/90
- A01N33/20
- A01N43/76

Information

Abstract

A synergistic microbicidal composition having two components. The first component is a nonionic surfactant with structure: R1O(CH2CH(CH3)O)5(CH2CH2O)9H, where R1 is a C8 alkyl group. The second component is cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride. The weight ratio of the nonionic surfactant to cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride is from 1:0.2 to 1:1.1429.

Description

This invention relates to microbicidal compositions containing cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride (CTAC), 4,4-dimethyloxazolidine (DMO) or tris(hydroxymethyl)nitromethane (Tris Nitro) and a surfactant.

A composition containing 5-chloro-2-methylisothiazolin-3-one, 2-methylisothiazolin-3-one and a nonionic dispersant is disclosed in U.S. Pat. No. 4,295,932. The composition contains a 3:1 mixture of 5-chloro-2-methylisothiazolin-3-one and 2-methylisothiazolin-3-one, and a copolymer of ethylene oxide and propylene oxide which appears to have the same composition as PLURONIC L61 or TERGITOL L61 dispersant. However, there is a need for combinations of microbicides having synergistic activity against various strains of microorganisms to provide effective control of the microorganisms. Moreover, there is a need for such combinations containing lower levels of individual microbicides for environmental and economic benefit. The problem addressed by this invention is to provide such synergistic combinations of microbicides.

STATEMENT OF THE INVENTION

The present invention is directed to a synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure:

- R¹O(CH₂CH(CH₃)O)₅(CH₂CH₂O)₉H
  
  where R¹is a C₈alkyl group; and (b) cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride; wherein a weight ratio of said nonionic surfactant to cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride is from 1:0.2 to 1:1.1429.

The present invention is further directed to a synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure:

- R²O(CH₂CH(CH₃)O)₃(CH₂CH₂O)₅H
  
  where R²is a mixture of C₈-C₁₄linear alkyl groups; and (b) cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride; wherein a weight ratio of said nonionic surfactant to cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride is from 1:0.04 to 1:0.9143.

The present invention is further directed to a synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure:

- R²O(CH₂CH(CH₃)O)₃(CH₂CH₂O)₇H
  
  where R²is a mixture of C₈-C₁₄linear alkyl groups; and (b) cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride; wherein a weight ratio of said nonionic surfactant to cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride is from 1:0.016 to 1:0.0571.

The present invention is further directed to a synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure:

- R¹O(CH₂CH(CH₃)O)₅(CH₂CH₂O)₉H
  
  where R¹is a C₈alkyl group; and (b) 4,4-dimethyloxazolidine; wherein a weight ratio of said nonionic surfactant to 4,4-dimethyloxazolidine is from 1:0.0286 to 1:0.1143 or 1:0.32 to 1:0.9143.

The present invention is further directed to a synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure:

- R²O(CH₂CH(CH₃)O)₃(CH₂CH₂O)₅H
  
  where R²is a mixture of C₈-C₁₄linear alkyl groups; and (b) 4,4-dimethyloxazolidine; wherein a weight ratio of said nonionic surfactant to 4,4-dimethyloxazolidine is from 1:0.06 to 1:0.6857.

The present invention is further directed to a synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure:

- R²O(CH₂CH(CH₃)O)₃(CH₂CH₂O)₇H
  
  where R²is a mixture of C₈-C₁₄linear alkyl groups; and (b) 4,4-dimethyloxazolidine; wherein a weight ratio of said nonionic surfactant to 4,4-dimethyloxazolidine is from 1:0.024 to 1:0.2743.

The present invention is further directed to a synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure:

- R²O(CH₂CH(CH₃)O)₃(CH₂CH₂O)₇H
  
  where R²is a mixture of C₈-C₁₄linear alkyl groups; and (b) tris(hydroxymethyl)nitromethane; wherein a weight ratio of said nonionic surfactant to tris(hydroxymethyl)nitromethane is from 1:0.16 to 1:1.8286.

The present invention is further directed to methods for inhibiting the growth of microorganisms in aqueous media by adding to an aqueous medium a nonionic surfactant as described herein and cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride, 4,4-dimethyloxazolidne or tris(hydroxymethyl)nitromethane in the ratios described herein.

DETAILED DESCRIPTION OF THE INVENTION

“CTAC” is cis-1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride, CAS No. 51229-78-8, “DMO” is 4,4-dimethyloxazolidine, CAS No. 51200-87-4, and “Tris Nitro” is tris(hydroxymethyl)nitromethane, CAS No. 126-11-4. As used herein, the following terms have the designated definitions, unless the context clearly indicates otherwise. The term “microbicide” refers to a compound capable of inhibiting the growth of or controlling the growth of microorganisms; microbicides include bactericides, fungicides and algaecides. 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.), references to percentages are percentages by weight (wt %) and amounts and ratios are on an active ingredient basis, i.e., total weight of CTAC and the nonionic surfactant. Numbers of polymerized units of propylene oxide or ethylene oxide are number averages.

Preferably, the weight ratio of the nonionic surfactant with structure:

- R¹O(CH₂CH(CH₃)O)₅(CH₂CH₂O)₉H
  
  where R¹is a C₈alkyl group to CTAC is from 1:0.2857 to 1:1.1429, preferably from 1:0.5714 to 1:1.1429. Preferably, the weight ratio of the nonionic surfactant with structure:
- R²O(CH₂CH(CH₃)O)₃(CH₂CH₂O)₅H
  
  where R²is a mixture of C₈-C₁₄linear alkyl groups to CTAC is from 1:0.0457 to 1:0.9143.

The present invention is further directed to a method for inhibiting the growth of S. aureus, in an aqueous medium by adding: (a) a nonionic surfactant with structure:

- R²O(CH₂CH(CH₃)O)₃(CH₂CH₂O)₅H
  
  where R²is a mixture of C₈-C₁₄linear alkyl groups; and (b) CTAC; wherein a weight ratio of said nonionic surfactant to CTAC is from 1:0.0457 to 1:0.9143.

The present invention is further directed to a method for inhibiting the growth of S. aureus, in an aqueous medium by adding: (a) a nonionic surfactant with structure:

- R²O(CH₂CH(CH₃)O)₃(CH₂CH₂O)₇H
  
  where R²is a mixture of C₈-C₁₄linear alkyl groups; and (b) Tris Nitro; wherein a weight ratio of said nonionic surfactant to Tris Nitro is from 1:0.16 to 1:1.8286.

R²is a mixture of C₈-C₁₄linear alkyl groups. Preferably, the C₈-C₁₄linear alkyl groups comprise from 50 to 85 wt % C₈-C₁₀linear alkyl groups and 15 to 50 wt % C₁₂-C₁₄linear alkyl groups, preferably from 60 to 75 wt % C₈-C₁₀linear alkyl groups and 25 to 40 wt % C₁₂-C₁₄linear alkyl groups, preferably about 70 wt % C₈-C₁₀linear alkyl groups and about 30 wt % C₁₂-C₁₄linear alkyl groups. Preferably, the linear alkyl groups are derived from seed oil. Preferably, R¹is 2-ethylhexyl.

Preferably, each of the compositions is substantially free of microbicides other than the nonionic surfactant and CTAC, DMO or Tris Nitro, i.e., it has less than 1 wt % of microbicides other than the nonionic surfactant and CTAC, DMO or Tris Nitro based on total weight of active ingredients, preferably less than 0.5 wt %, preferably less than 0.2 wt %, preferably less than 0.1 wt %. Preferably, when the nonionic surfactant and CTAC, DMO or Tris Nitro are added to an aqueous medium, the medium is substantially free of other microbicides, i.e., it has less than 1 wt % of microbicides other than the nonionic surfactant and CTAC, DMO or Tris Nitro based on total weight of active ingredients, preferably less than 0.5 wt %, preferably less than 0.2 wt %, preferably less than 0.1 wt %.

The compositions of this invention may contain other ingredients, e.g., defoamers and emulsifiers. The microbicidal compositions of the present invention can be used to inhibit the growth of microorganisms or higher forms of aquatic life (such as protozoans, invertebrates, bryozoans, dinoflagellates, crustaceans, mollusks, etc) by introducing a microbicidally effective amount of the compositions into an aqueous medium subject to microbial attack. Suitable aqueous media are found in, for example: industrial process water; electrocoat deposition systems; cooling towers; air washers; gas scrubbers; mineral slurries; wastewater treatment; ornamental fountains; reverse osmosis filtration; ultrafiltration; ballast water; evaporative condensers; heat exchangers; pulp and paper processing fluids and additives; starch; plastics; emulsions; dispersions; paints; latices; coatings, such as varnishes; construction products, such as mastics, caulks, and sealants; construction adhesives, such as ceramic adhesives, carpet backing adhesives, and laminating adhesives; industrial or consumer adhesives; photographic chemicals; printing fluids; household products, such as bathroom and kitchen cleaners; cosmetics; toiletries; shampoos; soaps; personal care products such as wipes, lotions, sunscreen, conditioners, creams, and other leave-on applications; detergents; industrial cleaners; floor polishes; laundry rinse water; metalworking fluids; conveyor lubricants; hydraulic fluids; leather and leather products; textiles; textile products; wood and wood products, such as plywood, chipboard, flakeboard, laminated beams, oriented strandboard, hardboard, and particleboard; petroleum processing fluids; fuel; oilfield fluids, such as injection water, fracture fluids, and drilling muds; agriculture adjuvant preservation; surfactant preservation; medical devices; diagnostic reagent preservation; food preservation, such as plastic or paper food wrap; food, beverage, and industrial process pasteurizers; toilet bowls; recreational water; pools; and spas.

The specific amount of the microbicidal compositions of this invention necessary to inhibit or control the growth of microorganisms in an application will vary. Typically, the amount of the composition of the present invention is sufficient to control the growth of microorganisms if it provides from 300 to 10,000 ppm (parts per million) active ingredients of the composition. It is preferred that the active ingredients (i.e., nonionic surfactant and CTAC, DMO or Tris Nitro) of the composition be present in the medium to be treated in an amount of at least 500 ppm, preferably at least 600 ppm, preferably at least 800 ppm. It is preferred that the active ingredients of the composition be present in the locus in an amount of no more than 6,000 ppm, preferably no more than 5,000 ppm, preferably no more than 4,000 ppm, preferably no more than 3,000 ppm, preferably no more than 2,500 ppm, preferably no more than 2,000 ppm. In a method of this invention, a composition is treated to inhibit microbial growth by adding, together or separately, the nonionic surfactant and CTAC, DMO or Tris Nitro, in amounts that would produce the concentrations indicated above.

EXAMPLES

Surfactants and biocides were evaluated for synergy by determining the synergy index (S.I.) of the combination. Synergy index was calculated based on minimum inhibitory concentrations (MIC) of two antimicrobial compounds (A and B) alone and in combinations. The tests organisms were Gram negative bacteria (Pseudomonas aeruginosa ATCC #15442), Gram positive bacteria (Staphylococcus aureus ATCC #6538), yeast (Candida albicans ATCC #10203) and mold (Aspergillus niger ATCC #16404). Contact time for the bacteria was 24 and 48 hours, yeast was 48 and 72 hrs, and 3 and 7 days for mold. The test was carried out in 96 well microtiter plates.

Surf. A R¹O(CH₂CH(CH₃)O)₅(CH₂CH₂O)₉H, where R¹is 2-ethylhexyl

Surf. D R²O(CH₂CH(CH₃)O)₃(CH₂CH₂O)₅H

Surf. E R²O(CH₂CH(CH₃)O)₃(CH₂CH₂O)₇H

In Surf. D and Surf. E, R²is a mixture of C₈-C₁₄linear alkyl groups (70% C₈-C₁₀linear alkyl and 30% C₁₂-C₁₄linear alkyl)

Inoculums Used

Inoculum Size of organisms (CFU/ml)

Aspergillus

Candida

Staphylococcus

Pseudomonas

niger

albicans

Surfac-

aureus

aeruginosa

ATCC#
ATCC#

tants
ATCC# 6538
ATCC # 15442
16404
10203

Surf. A
1.156E+06
8.134E+07
1.156E+06
1.156 +06

Surf. D
1.808E+05
1.156E+08
1.156E+06
5.726E+05

Surf. E
1.808E+06
5.727E+07
5.726E+05
1.808E+06

TABLE 4

Media Used

Media Used for testing

Staphylococcus

Pseudomonas

Aspergillus

Candida

aureus

aeruginosa ATCC #

niger

albicans

ATCC# 6538
15442
ATCC# 16404
ATCC# 10203

10% Tryptic soy
10% Tryptic soy
Potato dextrose
Potato dextrose

broth
broth
broth
broth

The pH of the Triptic soy broth was 7.3 and the Potato dextrose broth was 5.1.

The test results for demonstration of synergy of the MIC combinations are shown in the tables below. Each table shows the results for combinations of two components against the microorganisms tested with incubation times; the end-point activity in ppm measured by the MIC for compound A alone (CA), for component B alone (CB), and the mixture (Ca) and (Cb); the calculated SI value; and the range of synergistic ratios for each combination tested. SI is calculated as follows:

Ca/CA+Cb/CB=Synergy Index (“SI”)

Wherein:

- CA=concentration of compound A in ppm, acting alone, which produced an end point (MIC of Compound A).
- Ca=concentration of compound A in ppm, in the mixture, which produced an end point.
- CB=concentration of compound B in ppm, acting alone, which produced an end point (MIC of Compound B).
- Cb=concentration of compound B in ppm, in the mixture, which produced an end point.
  
  When the sum of Ca/CA and Cb/CB is greater than one, antagonism is indicated. When the sum is equal to one, additivity is indicated, and when less than one, synergism is demonstrated.

The ratio ranges at which CTAC, DMO or Tris Nitro and the surfactants were tested are as summarized in the following tables:

Organism
ATCC#
From
To
Ratio Range

CTAC with Surf. A

Staphylococcus aureus

6538
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Aspergillus niger

16404
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Candida albicans

10203
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Pseudomonas aeruginosa

15442
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

CTAC with Surf. E

Staphylococcus aureus

6538
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Aspergillus niger

16404
2.0:20,000
10,000:218.75
1:0.0001-1:45.7143

Candida albicans

10203
2.0:20,000
10,000:218.75
1:0.0001-1:45.7143

Pseudomonas aeruginosa

15442
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

CTAC with Surf. D

Staphylococcus aureus

6538
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Aspergillus niger

16404
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Candida albicans

10203
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Pseudomonas aeruginosa

15442
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Organism
ATCC#
From
To
Ratio Range

DMO with Surf. A

Staphylococcus

6538
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

aureus

Aspergillus

16404
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

niger

Candida

10203
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

albicans

Pseudomonas

15442
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

aeruginosa

DMO with Surf. E

Staphylococcus

6538
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

aureus

Aspergillus

16404
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

niger

Candida

10203
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

albicans

Pseudomonas

15442
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

aeruginosa

DMO with Surf. D

Staphylococcus

6538
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

aureus

Aspergillus

16404
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

niger

Candida

10203
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

albicans

Pseudomonas

15442
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

aeruginosa

Organism
ATCC#
From
To
Ratio Range

TrisNitro with Surf. A

Staphylococcus aureus

6538
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Aspergillus niger

16404
0.02:20,000
100:218.75
1:0.000001-1:0.45714

Candida albicans

10203
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Pseudomonas aeruginosa

15442
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

TrisNitro with Surf. E

Staphylococcus aureus

6538
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Aspergillus niger

16404
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Candida albicans

10203
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Pseudomonas aeruginosa

15442
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

TrisNitro with Surf. D

Staphylococcus aureus

6538
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Aspergillus niger

16404
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Candida albicans

10203
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

Pseudomonas aeruginosa

15442
0.2:20,000
1,000:218.75
1:0.00001-1:4.5714

A: Surf. A

B: CTAC

Media: PDB

Inoculum size: 1.156E+06

A. niger

ATCC#16404
No Synergy

C. albicans

ATCC#10203
No Synergy

A: Surf. A

B: CTAC

Media: 1/10 TSB

Inoculum size: 1.156E+06

S. aureus

ATCC# 6538
No Synergy

A: Surf. A

B: CTAC

Media: 1/10 TSB

Inoculum size: 1.156E+06

PPM AI MIC Values (3^rdDay)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

P. aeruginosa

>20000
600
20000
500
<1.83
1:0.0250

ATCC#15442
>20000
600
10000
500
<1.33
1:0.0500

>20000
600
5000
500
<1.08
1:0.1000

>20000
600
2500
500
<0.96
1:0.2000

>20000
600
1750
500
<0.92
1:0.2857

>20000
600
875
500
<0.88
1:0.5714

>20000
600
437.5
500
<0.86
1:1.1429

A: Surf. D

B: CTAC

Media: PDB

Inoculum size: 1.156E+06

PPM AI MIC Values (3rd day)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

A. niger

>20000
1000
10000
600
<1.10
1:0.0600

>20000
1000
10000
800
<1.30
1:0.0800

ATCC#16404
>20000
1000
5000
800
<1.05
1:0.1600

>20000
1000
2500
800
<0.93
1:0.3200

>20000
1000
1750
800
<0.89
1:0.4571

>20000
1000
875
800
<0.84
1:0.9143

A: Surf. D

B: CTAC

Media: PDB

Inoculum size: 5.726E+05 CFU/ml

PPM AI MIC Values (48 hrs)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

C. albicans

>20000
1000
10000
400
<0.90
1:0.0400

ATCC#10203
>20000
1000
10000
500
<1.00
1:0.0500

>20000
1000
10000
600
<1.10
1:0.0600

>20000
1000
10000
800
<1.30
1:0.0800

>20000
1000
5000
400
<0.65
1:0.0800

>20000
1000
5000
500
<0.75
1:0.1000

>20000
1000
5000
600
<0.85
1:0.1200

>20000
1000
5000
800
<1.05
1:0.1600

A: Surf. D

B: CTAC

Media: 1/10 TSB

Inoculum size: 1.808E+05

PPM AI MIC Values (24 hrs)

Test
Alone
Combination

Ratio

Organism
CA
CB
Ca
Cb
S.I.
(Ca:Cb)

S. aureus

>20000
300
10000
80
<0.77
1:0.0080

ATCC# 6538
>20000
300
10000
100
<0.83
1:0.0100

>20000
300
10000
200
<1.17
1:0.0200

>20000
300
5000
200
<0.92
1:0.0400

>20000
300
5000
80
<0.52
1:0.0160

>20000
300
5000
100
<0.58
1:0.0200

>20000
300
1750
80
<0.35
1:0.0457

>20000
300
1750
100
<0.42
1:0.0571

>20000
300
1750
200
<0.75
1:0.1143

>20000
300
875
200
<0.71
1:0.2286

>20000
300
437.5
200
<0.69
1:0.9143

>20000
300
218.75
200
<0.68
1:0.2286

A: Surf. D

B: CTAC

Media: 1/10 TSB

Inoculum size: 1.156E+06

P. aeruginosa

ATCC#15442
No Synergy

A: Surf. E

B: CTAC

Media: PDB

Inoculum 1.808E+05

A. niger

ATCC 16404
No synergy

A: Surf. E

B: CTAC

Media: PDB

Inoculum 1.808E+05

PPM AI MIC Values (48 hrs)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

C. albicans

>20000
2997
10000
1999
<1.17
1:0.1999

ATCC 10203

A: Surf. E

B: CTAC

Media: 1/10 TSB

Inoculum size: 5.72E+07

P. aeruginosa

ATCC#15442
No synergy

A: Surf. E

B: CTAC

Media: 1/10 TSB

Inoculum size: 1.8E+06

PPM AI MIC Values (24 hrs)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

S. aureus

>20000
200
10000
80
<0.90
1:0.0080

ATCC# 6538
>20000
200
10000
100
<1.00
1:0.0100

>20000
200
5000
80
<0.65
1:0.0160

>20000
200
5000
100
<0.75
1:0.0200

>20000
200
2500
100
<0.63
1:0.0400

>20000
200
1750
100
<0.59
1:0.0571

A: Surf. A

B: Tris Nitro

No synergy:

S. aureus, A. niger, C. albicans, Ps. aeruginosa

A: Surf. D

B: TrisNitro

Media: 1/10 TSB

Inoculum size: 1.16E+08

PPM AI MIC Values (24 hrs)

Test
Alone
Combination

Ratio

Organism
CA
CB
Ca
Cb
S.I.
(Ca:Cb)

Ps. aeruginosa

>20000
800
20000
1000
<2.25
1:0.0500

ATCC#15442
>20000
800
10000
1000
<1.75
1:0.1000

>20000
800
5000
1000
<1.50
1:0.2000

>20000
800
2500
800
<1.13
1:0.3200

>20000
800
1750
1000
<1.34
1:0.5714

>20000
800
875
800
<1.04
1:0.9143

>20000
800
437.5
600
<0.77
1:1.3714

>20000
800
437.5
800
<1.02
1:1.8286

>20000
800
218.75
800
<1.01
1:3.6571

No synergy: S. aureus, A. niger, C. albicans

A: Surf. E

B: TrisNitro

Media: 1/10TSB

Inoculum size: 5.727E+07 CFU/ml

PPM AI MIC Values (24 hrs)

Test
Alone
Combination

Ratio

Organism
CA
CB
Ca
Cb
S.I.
(Ca:Cb)

Ps. aeruginosa

>20000
1000
20000
1000
<2.00
1:0.0500

ATCC#15442
>20000
1000
10000
1000
<1.50
1:0.1000

>20000
1000
5000
1000
<1.25
1:0.2000

>20000
1000
2500
1000
<1.13
1:0.4000

>20000
1000
1750
1000
<1.09
1:0.5714

>20000
1000
875
1000
<1.04
1:1.1429

>20000
1000
437.5
800
<0.82
1:1.8286

>20000
1000
437.5
1000
<1.02
1:2.2857

>20000
1000
218.75
800
<0.81
1:3.6571

>20000
1000
218.75
1000
<1.01
1:4.5714

A: Surf. E

B: TrisNitro

Media: 1/10TSB

Inoculum size: 1.808E+06 CFU/ml

PPM AI MIC Values (24 hrs)

Test
Alone
Combination

Ratio

Organism
CA
CB
Ca
Cb
S.I.
(Ca:Cb)

S. aureus

>20000
500
20000
500
<2.00
1:0.0250

ATCC# 6538
>20000
500
10000
400
<1.30
1:0.0400

>20000
500
5000
400
<1.05
1:0.0800

>20000
500
2500
400
<0.93
1:0.1600

>20000
500
1750
300
<0.69
1:0.1714

>20000
500
1750
400
<0.89
1:0.2286

>20000
500
875
400
<0.84
1:0.4571

>20000
500
437.5
400
<0.82
1:0.9143

>20000
500
218.75
400
<0.81
1:1.8286

>20000
500
218.75
500
<1.01
1:2.2857

No synergy: A. niger, C. albicans

A: Surf. A

B: DMO

Media: PDB

Inoculum size: 1.156E+06 CFU/ml

PPM AI MIC Values (3^rdDay)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

A. niger

>20000
60
10000
50
<1.33
1:0.0050

ATCC#16404
>20000
60
5000
50
<1.08
1:0.0100

>20000
60
2500
50
<0.96
1:0.0200

>20000
60
1750
50
<0.92
1:0.0286

>20000
60
875
50
<0.88
1:0.0571

>20000
60
437.5
50
<0.86
1:0.1143

A: Surf. A

B: DMO

Media: PDB

Inoculum size: 1.156E+06 CFU/ml

PPM AI MIC Values (3^rdDay)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

C. albicans

>20000
1000
10000
800
<1.30
1:0.0800

ATCC#10231
>20000
1000
5000
800
<1.05
1:0.1600

>20000
1000
2500
800
<0.93
1:0.3200

>20000
1000
875
800
<0.84
1:0.9143

A: Surf. A

B: DMO

Media: 1/10 TSB

Inoculum size: 8.134+07 CFU/ml

PPM AI MIC Values (24 hrs)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

P. aeruginosa

>20000
80
20000
60
<1.75
1:0.0030

ATCC#15442

A: Surf. A

B: DMO

Media: 1/10 TSB

Inoculum size: 1.156E+06 CFU/ml

PPM AI MIC Values (24 hrs)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

S. aureua

>20000
50
20000
40
<1.80
1:0.0020

ATCC#6538

A: Surf. D

B: DMO

Media: 1/10 TSB

Inoculum size: 1.16E+08

P. aeruginosa

ATCC#15442
No Synergy

A: Surf. D

B: DMO

Media: PDB

Inoculum size: 1.156E+06

PPM AI MIC Values (3rd day)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

A. niger

>20000
400
10000
300
<1.25
1:0.0300

ATCC#16404
>20000
400
5000
300
<1.0
1:0.0600

>20000
400
437.5
300
<0.77
1:0.6857

A: Surf. D

B: DMO

Media: PDB

Inoculum size: 5.726E+05 CFU/ml

PPM AI MIC Values (48 hrs)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

C. albicans

>20000
1000
10000
800
<1.30
1:0.0800

ATCC#10231
>20000
1000
5000
800
<1.05
1:0.1600

A: Surf. D

B: 1135

Media: 1/10 TSB

Inoculum size: 1.16E+08

PPM AI MIC Values (24 hrs)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

S. aureus

>20000
80
10000
50
>1.13
1:0.0050

ATCC#6538
>20000
80
10000
60
>1.25
1:0.0060

>20000
80
5000
50
<0.88
1:0.0100

>20000
80
5000
60
<1.00
1:0.0025

>20000
80
2500
60
<0.88
1:0.0120

>20000
80
1750
50
<0.71
1:0.0240

>20000
80
1750
60
<0.84
1:0.0286

>20000
80
875
50
<0.67
1:0.0343

>20000
80
875
60
<0.79
1:0.0571

>20000
80
437.5
50
<0.65
1:0.0686

>20000
80
437.5
60
<0.77
1:0.1143

>20000
80
218.75
60
<0.76
1:0.1371

A: Surf. E

B: DMO

Media: PDB

Inoculum size: 1.808E+06

PPM AI MIC Values (48 hrs)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

C. albicans

>20000
1000
10000
600
<1.10
1:0.0600

ATCC#10203
>20000
1000
10000
800
<1.30
1:0.0800

>20000
1000
5000
600
<0.85
1:0.1200

>20000
1000
5000
800
<1.05
1:0.1600

A: Surf. E

B: DMO

Media: PDB

P. aeruginosa

ATCC#15442
No Synergy

A: Surf. E

B: DMO

Media: PDB

Inoculum size: 1.56E+06 CFU/ml

PPM AI MIC Values (3^rdDay)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

A. niger

>20000
800
10000
600
<1.25
1:0.0600

ATCC#16404
>20000
800
5000
600
<1.00
1:0.1200

>20000
800
437.5
600
<0.77
1:1.3714

A: Surf. E

B: DMO

Media: 1/10 TSB

Inoculum size: 1.80E+06 CFU/ml

PPM AI MIC Values (24 hrs)

Test
Alone
Combination

Organism
CA
CB
Ca
Cb
S.I.
Ratio (Ca:Cb)

ATCC#6538
>20000
80
10000
50
<1.13
1:0.0050

>20000
80
10000
60
<1.25
1:0.0060

>20000
80
5000
50
<0.88
1:0.0100

>20000
80
5000
60
<1.00
1:0.0120

>20000
80
2500
60
<0.88
1:0.0240

>20000
80
1750
60
<0.84
1:0.0343

>20000
80
875
60
<0.79
1:0.0686

>20000
80
437.5
50
<0.65
1:0.1143

>20000
80
437.5
60
<0.77
1:0.1371

>20000
80
218.75
60
<0.76
1:0.2743

The following biocides had no synergy against any organism tested when paired with the following surfactants:

Surf. A

Sodium Benzoate, TRIS NITRO

Surf. E

DMDMH

Surf. D

CS-1246, OPP, DMDMH

In the following combinations, the ratio of surfactant to biocide where synergy was observed were not commercially relevant, i.e., a ratio of 1:0.2 or greater (less biocide relative to surfactant). At these ratios, the biocide levels in a formulated product would be too low to be practical:

Surf. A

DIDAC, IPBC

Surf. E

CMIT/MIT, IPBC, OIT, TTPC, WSCP

Surf. D

CMIT/MIT, OIT, DIDAC

(MBIT, IPBC, WSCP were synergistic only at 1:0.05 or worse except for one data point)

Claims

1. A synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure: R1O(CH2CH(CH3)O)5(CH2CH2O)9H
2. The synergistic microbicidal composition of claim 1 in which R1 is 2-ethylhexyl.
3. A synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure: R2O(CH2CH(CH3)O)3(CH2CH2O)5H
4. The synergistic microbicidal composition of claim 3 in which said mixture of C8-C14 linear alkyl groups comprises from 60 to 75 wt % C8-C10 linear alkyl groups and 25 to 40 wt % C12-C14 linear alkyl groups.
5. A synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure: R1O(CH2CH(CH3)O)5(CH2CH2O)9H
6. The synergistic microbicidal composition of claim 5 in which R1 is 2-ethylhexyl.
7. A synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure: R2O(CH2CH(CH3)O)3(CH2CH2O)5H
8. The synergistic microbicidal composition of claim 7 in which said mixture of C8-C14 linear alkyl groups comprises from 60 to 75 wt % C8-C10 linear alkyl groups and 25 to 40 wt % C12-C14 linear alkyl groups.
9. A synergistic microbicidal composition comprising: (a) a nonionic surfactant with structure: R2O(CH2CH(CH3)O)3(CH2CH2O)7H
10. The synergistic microbicidal composition of claim 9 in which. said mixture of C8-C14 linear alkyl groups comprises from 60 to 75 wt % C8-C10 linear alkyl groups and 25 to 40 wt % C12-C14 linear alkyl groups.

PCT Information

Filing Document	Filing Date	Country	Kind
PCT/US2014/058953	10/3/2014	WO	00

Provisional Applications (1)

	Number	Date	Country
	61886340	Oct 2013	US