# Patent

## Title
Synergistic combination of flumetsulam or diclosulam with isothiazolones

## Abstract

A synergistic antimicrobial composition containing flumetsulam and an isothiazolone biocide chosen from among 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, 2-n-octyl-4-isothiazolin-3-one and N-n-butyl-1,2-benzisothiazolin-3-one. A synergistic antimicrobial composition containing diclosulam and an isothiazolone biocide chosen from 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one and 2-n-octyl-4-isothiazolin-3-one.

## Background
This invention relates to combinations of biocides, the combinations having greater activity than would be observed for the individual antimicrobial compounds.
Use of combinations of at least two antimicrobial compounds can broaden potential markets, reduce use concentrations and costs, and reduce waste. In some cases, commercial antimicrobial compounds cannot provide effective control of microorganisms, even at high use concentrations, due to weak activity against certain types of microorganisms, e.g., those resistant to some antimicrobial compounds. Combinations of different antimicrobial compounds are sometimes used to provide overall control of microorganisms in a particular end use environment. For example, U.S. Pat. No. 5,591,760 discloses a combination of 3-iodo-2-propynyl-butylcarbamate (IPBC) and 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT), but this reference does not suggest any of the combinations claimed herein. Moreover, there is a need for additional combinations of antimicrobial compounds having enhanced activity against various strains of microorganisms to provide effective control of the microorganisms, especially in dry film coatings. The problem addressed by this invention is to provide such additional combinations of antimicrobial compounds.
STATEMENT OF THE INVENTION
The present invention is directed to a synergistic antimicrobial composition comprising: (a) flumetsulam; and (b) an isothiazolone biocide selected from the group consisting of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, 2-n-octyl-4-isothiazolin-3-one (OIT) and N-n-butyl-1,2-benzisothiazolin-3-one (BBIT); wherein a weight ratio of flumetsulam to 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one is from 15:1 to 1:15, a weight ratio of flumetsulam to 2-n-octyl-4-isothiazolin-3-one is from 7:1 to 1:5 and a weight ratio of flumetsulam to N-n-butyl-1,2-benzisothiazolin-3-one is from 15:1 to 1:15.
The present invention is further directed to a synergistic antimicrobial composition comprising: (a) diclosulam; and (b) an isothiazolone biocide selected from the group consisting of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one and 2-n-octyl-4-isothiazolin-3-one; wherein a weight ratio of diclosulam to 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one is from 7:1 to 1:3 and a weight ratio of diclosulam to 2-n-octyl-4-isothiazolin-3-one is from 7:1 to 1:1.5 or 1:3 to 1:7.


DETAILED DESCRIPTION OF THE INVENTION
As used herein, the following terms have the designated definitions, unless the context clearly indicates otherwise. Fluometsulam is N-(2,6-difluorophenyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide. Diclosulam is N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide. The term “antimicrobial compound” refers to a compound capable of inhibiting the growth of or controlling the growth of microorganisms; antimicrobial compounds include bactericides, bacteristats, fungicides, fungistats, algaecides and algistats, depending on the dose level applied, system conditions and the level of microbial control desired. The term “microorganism” includes, for example, fungi (such as yeast and mold), bacteria and algae. The following abbreviations are used throughout the specification: ppm=parts per million by weight (weight/weight), mL=milliliter, ATCC=American Type Culture Collection, and MIC=minimum inhibitory concentration. Unless otherwise specified, temperatures are in degrees centigrade (° C.), and references to percentages are by weight (wt %). Percentages of antimicrobial compounds in the composition of this invention are based on the total weight of active ingredients in the composition, i.e., the antimicrobial compounds themselves, exclusive of any amounts of solvents, carriers, dispersants, stabilizers or other materials which may be present.
Preferably, when the antimicrobial composition comprises flumetsulam and DCOIT, a weight ratio of flumetsulam to DCOIT is from 15:1 to 1:12, preferably from 12:1 to 1:12, preferably from 12:1 to 1:10; preferably from 10:1 to 1:10.
Preferably, when the antimicrobial composition comprises flumetsulam and OIT, a weight ratio of flumetsulam to OIT is from 7:1 to 1:4; preferably from 6:1 to 1:4; preferably from 7:1 to 1:3; preferably from 6:1 to 1:3; preferably from 5:1 to 1:3.
Preferably, when the antimicrobial composition comprises flumetsulam and BBIT, a weight ratio of a weight ratio of flumetsulam to BBIT is from 15:1 to 1:12; preferably from 12:1 to 1:12; preferably from 12:1 to 1:10; preferably from 10:1 to 1:10.
Preferably, when the antimicrobial composition comprises diclosulam and DCOIT, a weight ratio of diclosulam to DCOIT is from 6:1 to 1:3; preferably from 5:1 to 1:3; preferably from 6:1 to 1:2; preferably from 5:1 to 1:2.
Preferably, when the antimicrobial composition comprises diclosulam and OIT, a weight ratio of diclosulam to OIT is from 7:1 to 1:1.5 or 1:3 to 1:6; preferably from 6:1 to 1:1.5 or 1:3 to 1:6; preferably from 5:1 to 1:1.5 or 1:3 to 1:5; preferably from 7:1 to 1:1 or 1:3 to 1:5; preferably from 6:1 to 1:1 or 1:3 to 1:5; preferably from 5:1 to 1:1 or 1:3 to 1:5; preferably from 5:1 to 1:1; preferably from 5:1 to 2:1.
Preferably, flumetsulam in combination with DCOIT and/or OIT is used to inhibit growth of fungi in an aqueous medium. Preferably, the ratio of flumetsulam to DCOIT is from 15:1 to 1:4; preferably from 12:1 to 1:4; preferably from 12:1 to 1:3; preferably from 10:1 to 1:3; preferably from 10:1 to 1:2. Preferably, the ratio of flumetsulam to OIT is from from 7:1 to 1:4; preferably from 6:1 to 1:4; preferably from 7:1 to 1:3; preferably from 6:1 to 1:3; preferably from 5:1 to 1:3.
The antimicrobial compositions described above may contain more than one of the listed isothiazolone biocides and/or other biocides.
Preferably, the antimicrobial combinations of this invention are incorporated into liquid compositions, especially dispersions of polymers in aqueous media. The biocide combinations are particularly useful in preservation of building materials, e.g., adhesives, caulk, joint compound, sealant, wallboard, etc), paints, coatings, polymers, plastics, synthetic and natural rubber, paper products, fiberglass sheets, insulation, exterior insulating finishing systems, roofing and flooring felts, building plasters, wood products and wood-plastic composites. Preferably, the antimicrobial compositions are latex paints or other liquid coating compositions containing the biocide combinations disclosed herein. The biocide combinations are useful for preservation of the dry film coating resulting after application of a paint or other liquid coating composition. Preferably, the antimicrobial composition is an acrylic latex paint comprising one or more of the biocide combinations disclosed herein, or the dry film coating resulting from application of the paint to a surface.
Typically, the amount of the biocide combinations of the present invention to control the growth of microorganisms is from 100 ppm to 10,000 ppm active ingredient. Preferably, the active ingredients of the composition are present in an amount of at least 300 ppm, preferably at least 500 ppm, preferably at least 600 ppm, preferably at least 700 ppm. Preferably, the active ingredients of the composition are present in an amount of no more than 8,000 ppm, preferably 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 2500 ppm, preferably no more than 2,000 ppm, preferably no more than 1,800 ppm, preferably no more than 1,600 ppm. Concentrations mentioned above are in a liquid composition containing the biocide combinations; biocide levels in the dry film coating will be higher.
The present invention also encompasses a method for preventing microbial growth in building materials, especially in dry film coatings, by incorporating any of the claimed biocide combinations into the materials.
EXAMPLES
Sample Preparation:
A single or blend of biocides was post added into white acrylic latex paint free of biocides to give a maximum total active ingredient/s concentration tested. This paint was then diluted with a biocide free acrylic latex paint to give targeted concentrations for the testing. Depending on the type of biocide blends tested, the total biocides concentrations varies from 200 to 5000 ppm. After biocides addition or dilution, each sample was hand mixed for at least a minute until uniformity is achieved. Each of the paint samples as well as a control sample (containing no biocide) were used to prepare films on black plastic-vinyl chloride/acetate copolymer panels (LENETA, Mahwah, N.J.) using a 3 mil (0.0762 mm) bird bar applicator. The panels were thoroughly dried for at least 2 days avoiding direct exposure to sunlight. Square discs (0.5 inch; 1.27 cm2) were cut out from each panel and were used as the substrate for fungal and algal efficacy tests. This sample size allowed for an agar border when the sample disc was placed into the well of the test plate. Each sample was tested in duplicate
Test Conditions:
The appropriate media (BOLD'S 3N for Chlorophytes, BG-11 for Cyanobacteria, and PDA for fungi) were used to support microbial growth. The test plates were maintained at room temp (25° C.-26° C.), in a cycled light-dark environment, for four weeks for algae. Plates for fungal challenge tests were maintained at 30 C for four weeks. At the end of the incubation period the samples were scored for percent area covered by visible microbial growth.
Algal Inoculum


















Medium






for


Organisms
abbreviation

Type
testing







Gloeocapsa
Gs
ATCC 29159
Unicellular,
BG-11


sp.


Colonial





Cyanobacteria


Oscillatoria
Os
ATCC 29135
Filamentous
BG-11


sp.


Cyanobacteria


Nostoc
Nc
CCAP 1453/29
Unicellular,
Bold


commune


Cenobial





Chlorophyte


Trentepohlia
Ta + To
UTEX LB 429 +
Filamentous
Bold


aurea +

CCAP 483/4
Chlorophyte


Trentepohlia


odorata


Chlorella sp.
Cs + Ck
ATCC 30582 +
Unicellular
Bold


UTEX +

ATCC 11468
Chlorophyte


Chlorella


kessleri


Calothrix
Cp
UTEX LB 1952
Filamentous
Bold


parientina


Cyanobacteria









Fungal Inoculum

















Medium for





Growth and


Organisms
abbreviation
ATCC#
Testing


















Aspergillus niger
An
9642
PDA


Penicillium funiculosum
Pf
11797
PDA


Cladosporium herbarum
Ch
11281
PDA


Aureobasidium pullulans
Ap
9348
PDA


Trichoderma viride
Tv
32630
PDA


Alternaria alternata
Aa
20084
PDA









Algal Efficacy Testing—Modified ASTM 5589

ASTM 5589 is a standard accelerated test method for determining resistance of various coatings (including paints) to algal defacement. To accommodate for high-throughput screening, this method was scaled down from petri plates to 6-well plates. A single coupon was placed with a pair of sterile forceps at the center of the agar plug (on top) with the painted surface facing upwards. Algal inoculums were prepared by mixing equal concentrations (1×106 cfu/ml) and equal volumes (depending on number of samples to be inoculated) of like growing organisms.
In Flumetsulam+various IT synergy study, three pool of mixed algae were prepared as the test inoculum, Gloeocapsa sp. and Oscillatoria sp. a mix of cyanobacteria grown on BG-11 media; Chlorella sp., Chlorella kessleri, and Nostoc commune are unicellular chlorphytes that were mixed and grown on Bold media; Trentepohlia aurea, Tretepohlia odorata, and Calotrix parientina are filamentous algae that were mixed and grown on Bold media.
In Diclosulam+various IT synergy study, only two pools of mixed algae were prepared; Gloeocapsa sp. and Oscillatoria sp. grown on BG-11 media and Chlorella sp., Chlorella kessleri, Nostoc commune, Trentepohlia aurea, Tretepohlia odorata, and Calotrix parientina grown on Bold media
Each well that contains a tested coupon was inoculated with 400 μl of organism mixture (1×106 cfu/ml) making sure that the whole surface (paint film as well as the agar surrounding it) was evenly covered. The plates were incubated at room temp (25° C.-26° C.) with cyclic exposure to light (OTT-Lite model #OTL4012P, 40 Watt, 26 KLumen) and dark phases, for a period of four weeks. The total area covered was evaluated at the end of each week according to percent area covered in 5% increments.
Fungal Efficacy Testing—Modified ASTM 5590
ASTM 5590 is a standard accelerated test method for determining resistance of various coatings (including paints) to fungal defacement. To accommodate for high-throughput screening, this method was scaled down from petri plates to 6-well plates. To set up the test, an agar plug was placed at the bottom of each well of the sterile 6-well plate. A single coupon was placed with a pair of sterile forceps at the center of the agar plug (on top) with the painted surface facing upwards. Fungal inoculums were prepared by mixing equal concentrations (1×106 cfu/ml) and equal volumes (depending on number of samples to be tested) of like growing organisms. For Flumetsulam+various IT synergy study, three pools of mixed fungi were prepared as the test inoculum. Cladosporium herbarum was mixed with Aureobasidium pullulans; Aspergillus niger was mixed with Penicillium funiculosum and Alternaria alternata was mixed with Trichoderma viride. For Diclosulam+various IT synergy study, all above fungi were mixed as a single pool. Each well was inoculated with 400 μl of organism mixture (1×106 cfu/ml) making sure that the whole surface (paint film as well as the agar surrounding it) was evenly covered. The plates were incubated at 30° C. in presence of moisture, for a period of four weeks. The total percent area covered was evaluated and recorded at the end of each week after the 2nd week and recorded in increments of 5%.
Synergy Index Calculation
Synergy Index (SI)
The SI is calculated based on F. C. Kull et. Al. method (Applied Microbiology, Vol. 9 (1961). In this study, SI was calculated based on the following formula with the minimum inhibitory concentration chosen based on the percent inhibitory exhibited by the individual biocide against each microorganisms tested.

SI=Qa/QA+Qb/QB 

Qa=the concentration of Biocide A in the blend
QA=The concentration of Biocide A as the only biocide
Qb=The concentration of Biocide B in the blend
QB=The concentration of Biocide B as the only biocide
SI value of <1 in the formula indicates a synergism of the blended biocides exists.
Note: If any of the active with maximum concentration tested did not exhibit some inhibition, this maximum concentration is used to calculate the estimated SI and a sign of less than (<) is included to take into account that higher concentration of the active is needed to achieve the targeted inhibition
NE=no end point at the concentration tested that will meet the percent inhibition criteria set in each SI calculation
Flumetsulam: DCOIT Synergy Study


















AaTv
AnPf
ApCh
Cp + To + Ta
Cs + Ck + Nc
Gs + Os






















1Flumet:1DCOIT








Total conc, ppm
1150
575
575
575
575
575


% inhibition
100
95
100
100
100
100


SI
<1.16
<0.58
0.6
2.7
0.4
2.1


2Flumet:1DCOIT


Total conc, ppm
2588
862.5
862.5
431.25
431.25
431.25


% inhibition
100.0
90
100
95
100
100


SI
<1.99
<0.66
0.7
1.7
0.3
1.1


3Flumet:1DCOIT


Total conc, ppm
1000
1000
1000
1000
1000
1000


% inhibition
100
100
100
100
95
1000


SI
<0.65
<0.65
0.7
3.5
0.7
2.0


5Flumet:1DCOIT


Total conc, ppm
750
1500
750
750
750
750


% inhibition
80
90
95
100
100
100


SI
<0.40
<0.7
0.4
2.3
0.5
1.1


10Flumet:1DCOIT


Total conc, ppm
1650
1650
825
825
1650
825


% inhibition
100
90
100
100
100
100


SI
<0.69
<0.69
0.3
2.2
1.0
0.8


1Flumet:2DCOIT


Total conc, ppm
888
444
444
444
444
444


% inhibition
90
100
100
95
100
100


SI
<1.11
<0.56
0.6
2.4
0.3
2.1


1Flumet:5DCOIT


Total conc, ppm
1380
690
690
690
690
690


% inhibition
100
100
100
100
100
100


SI
<2.1
<1.0
1.0
4.3
0.6
4.0


1Flumet:10DCOIT


Total conc, ppm
632.5
632.5
632.5
632.5
632.5
632.5


% inhibition
90
100
100
100
100
100


SI
<1.01
<1.0
1.0
4.1
0.5
4.0


Flumetsulam


Total conc, ppm
3500
3500
3500
437.5
1750
2625


% inhibition
0
0
90
95
100
100


DCOIT


Total conc, ppm
575
575
862.5
143.75
1150
143.75


% inhibition
85
100
100
100
100
100









Flumetsulam: OTT Synergy Study



















AaTv
AnPf
ApCh
Cp + To + Ta
Cs + Ck + Nc
Gs + Os






















1Flumet:1OIT








Total conc, ppm
750
750
750
750
750
750


% inhibition
100
100
100
100
100
100


SI
<0.50
0.9
<0.5
1.7
1.0
1.7


2Flumet:1OIT


Total conc, ppm
750
750
750
750
750
750


% inhibition
100.0
100
95
100
100
90


SI
<0.4
0.7
<0.4
1.7
0.7
1.7


3Flumet:1OIT


Total conc, ppm
750
750
1500
750
750
750


% inhibition
100
95
95
95
100
100


SI
<0.40
0.6
<0.70
1.7
0.6
7.0


5Flumet:1OIT


Total conc, ppm
1800
687.5
1800
687.5
687.5
687.5


% inhibition
100
95
100
90
100
95


SI
<0.80
0.3
<0.80
1.6
0.4
1.6


1Flumet:3OIT


Total conc, ppm
600
1200
600
600
600
600


% inhibition
100
100
90
100
100
95


SI
<0.5
2.1
<0.50
1.3
1.1
1.3


1Flumet:2OIT


Total conc, ppm
675
1350
675
675
675
675


% inhibition
100
100
100
100
100
100


SI
<0.60
2.1
<0.60
1.5
1.1
1.5


Flumetsulam


Total conc, ppm
3500
3500
3500
437.5
2625
437.5


% inhibition
0
65
0
60
65
90


OIT


Total conc, ppm
900
450
900
450
450
450


% inhibition
100
100
80
100
100
100









Flumetsulam: BBIT Synergy Study



















AaTv
AnPf
ApCh
Cp + To + Ta
Cs + Ck + Nc
Gs + Os






















1Flumet:1BBIT








Total conc, ppm
NE
575
575
NE
1150
575


% inhibition

60
80

80
100


SI

<0.33
<0.58

<0.66
<0.33


2Flumet:1BBIT


Total conc, ppm
NE
431
1725
NE
1725
1725


% inhibition

80
60

80
100


SI

<0.21
<1.32

<0.83
<0.83


3Flumet:1BBIT


Total conc, ppm
NE
1000
NE
NE
1000
3000


% inhibition

80


60
80


SI

<0.43


<0.43
<1.30


5Flumet:1BBIT


Total conc, ppm
NE
1500
NE
3000
3000
3000


% inhibition

80

60
60
60


SI

<0.57

1.2
<1.14
<1.15


10Flumet:1BBIT


Total conc, ppm
NE
825
NE
2475
1650
825


% inhibition

80

100
80
100


SI

<0.28

<0.84
<0.56
<0.28


1Flumet:1.8BBIT


Total conc, ppm
NE
887.5
NE
NE
887.5
887.5


% inhibition

80


60
60


SI

<0.59


<0.59
<0.59


1Flumet:5 BBIT


Total conc, ppm
NE
1035
NE
NE
690
690


% inhibition

80


100
60


SI

<0.8


<0.53
<0.53


1Flumet:10 BBIT


Total conc, ppm
NE
949
NE
NE
949
632.5


% inhibition

80


80
80


SI

<0.77


<0.77
<0.52


Flumetsulam


Total conc, ppm
3500
3500
3500
3500
3500
3500


% inhibition
0
0
0
0
0
0


BBIT


Total conc, ppm
1150
1150
575
1150
1150
1150


% inhibition
0
0
80
0
0
0









Synergy Study of Diclosulam and DCOIT















Aa + Tv + An +
Cp + To + Ta +



Ratios
Pf + Ap + Ch
Cs + Ck + Nc
Gs + Os


















1Diclosulam:1DCOIT





Total conc, ppm
575
575
575


% inhibition
85
100
100


SI
0.5
1.1
1.1


Dicolosulam:2DCOIT


Total conc, ppm
887.5
443.75
443.75


% inhibition
100
100
100


SI
1.0
0.8
0.8


1Diclosulam:5DCOIT


Total conc, ppm
690
690
690


% inhibition
95
100
100


SI
1.0
1.1
1.1


1Diclosulam:10DCOIT


Total conc, ppm
632.5
632.5
632.5


% inhibition
95
100
100


SI
0.9
1.0
1.0


2Diclosulam:1DCOIT


Total conc, ppm
862.5
443.75
443.75


% inhibition
87.5
100
100


SI
0.6
0.9
0.9


5Diclosulam:1DCOIT


Total conc, ppm
1500
750
750


% inhibition
85
100
100


SI
0.8
1.6
1.6


10Diclosulam:1DCOIT


Total conc, ppm
3300
825
825


% inhibition
90
100
100


SI
1.3
1.8
1.8


Diclosulam


Total conc, ppm
3500
437.5
437.5


% inhibition
40
100
100


DCOIT


Total conc, ppm
625
625
625


% inhibition
80
100
100









Synergy Study of Diclosulam+OIT















Aa + Tv +
Cp + To +



Ratios
An + Pf + Ap + Ch
Ta + Cs + Ck + Nc
Gs + Os


















1Diclosulam:1OIT





Total conc, ppm
750
2250
750


% inhibition
100
100
100


SI
<0.9
3.8
1.3


2Dicolosulam:1OIT


Total conc, ppm
750
2250
1500


% inhibition
80
100
100


SI
<0.7
4.3
2.8


3Diclosulam:1OIT


Total conc, ppm
750
2250
750


% inhibition
100
100
100


SI
<0.6
4.5
1.5


5Diclosulam:1OIT


Total conc, ppm
687.5
2700
687.5


% inhibition
100
80
100


SI
<0.3
5.6
1.5


1Diclosulam:3OIT


Total conc, ppm
600
600
600


% inhibition
100
100
100


SI
<1.0
1.0
0.8


1Diclosulam:2OIT


Total conc, ppm
675
675
675


% inhibition
100
100
100


SI
<1.1
1.0
1.0


1Diclosulam:5OIT


Total conc, ppm
540
1080
540


% inhibition
100
100
100


SI
1.0
1.4
0.7


1Diclosulam:10OIT


Total conc, ppm
990
990
990


% inhibition
100
100
100


SI
<2.0
1.2
1.2


Diclosulam


Total conc, ppm
3500
437.5
437.5


% inhibition
0
100
100


OIT


Total conc, ppm
450
900
900


% inhibition
100
100
100

## Claims

1. A synergistic antimicrobial composition comprising: (a) flumetsulam; and (b) an isothiazolone biocide selected from the group consisting of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, 2-n-octyl-4-isothiazolin-3-one and N-n-butyl-1,2-benzisothiazolin-3-one; wherein a weight ratio of flumetsulam to 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one is from 10:1 to 1:10, a weight ratio of flumetsulam to 2-n-octyl-4-isothiazolin-3-one is from 5:1 to 1:3 and a weight ratio of flumetsulam to N-n-butyl-1,2-benzisothiazolin-3-one is from 10:1 to 1:10.

2. The composition of claim 1 in which the isothiazolone biocide is 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one.

3. The composition of claim 1 in which the isothiazolone biocide is 2-n-octyl-4-isothiazolin-3-one.

4. The composition of claim 1 the isothiazolone biocide is N-n-butyl-1,2-benzisothiazolin-3-one.

5. A synergistic antimicrobial composition comprising: (a) diclosulam; and (b) an isothiazolone biocide selected from the group consisting of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one and 2-n-octyl-4-isothiazolin-3-one; wherein a weight ratio of diclosulam to 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one is from 5:1 to 1:2 and a weight ratio of diclosulam to 2-n-octyl-4-isothiazolin-3-one is from 5:1 to 1:1 or 1:3 to 1:5.

6. The composition of claim 5 in which the isothiazolone biocide is 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one.

7. The composition of claim 5 in which the isothiazolone biocide is 2-n-octyl-4-isothiazolin-3-one.

8. The composition of claim 1 which is a building material, paint, coating, polymer, plastic, synthetic or natural rubber, paper product, fiberglass sheet, insulation, exterior insulating finishing system, roofing and flooring felt, building plaster, wood product or wood-plastic composite.

9. The composition of claim 5 which is a building material, paint, coating, polymer, plastic, synthetic or natural rubber, paper product, fiberglass sheet, insulation, exterior insulating finishing system, roofing and flooring felt, building plaster, wood product or wood-plastic composite.