ANTI-MICROBIAL PAPER PRODUCTS HAVING A SUBSTITUTED 1,2-DIHYDROQUINOLINE

PRODUITS PAPIER ANTIMICROBIENS COMPRENANT UNE 1,2-DIHYDROQUINOLINE SUBSTITUEE

English Abstract

Anti-miorobial papers contain a substituted 1,2-dihydroquinoline compound.
Anti-microbial paper products, methods of making such materials, and materials
used to prepare such products involve the use of substituted 1,2-
dihydroquinoline compounds. The compounds can be within, or on the surface of,
the paper product. The compounds do not cause discoloration of the paper
products. Additionally, anti-oxidants may be in the composition.

French Abstract

La présente invention concerne de manière générale des produits papier antimicrobiens, des compositions comprenant des produits papier antimicrobiens, des procédés de fabrication de produits papier antimicrobiens, et des procédés d~inhibition de la croissance ou de la réplication microbienne dans des produits papier.

Claims

CLAIMS
What is Claimed is:
1. A process of producing a paper product, the process comprising
contacting a substituted 1,2-dihydroquinoline compound with a composition
comprising pulp.
2. The process of claim 1, further comprising forming a paper web from
the pulp; and drying the paper web.
3. The process of claim 2, further comprising forming the paper web from
the pulp by extracting water to define paper fibers having a plurality of
interstices, the
substituted 1,2-dihydroquinoline compound being deposited within the
interstices.
4. The process of claim 1, wherein the substituted 1,2-dihydroquinoline is
a compound having the formula:
<IMG>
wherein:
R1, R2, R3 and R4 are independently selected from the group consisting
of hydrogen and an alkyl group having from 1 to about 6 carbons;
R5 is an alkoxy group having from 1 to about 12 carbons.
5. The process of claim 1, wherein the substituted 1,2-dihydroquinoline
compound is 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline.
6. The process of claim 1, wherein the substituted 1,2-dihydroquinoline is
added to the pulp at a concentration of at least 300 ppm.

7. The process of claim 1, wherein the substituted 1,2-dihydroquinoline is
added to the pulp at a concentration of at least 0.1% by weight.
8. The process of claim 1, wherein the substituted 1,2-dihydroquinoline is
added to the pulp at a concentration from about 0.1% to about 6% by weight.
9. The process of claim 1, further comprising adding an additional agent
to the pulp, the agent selected from the group consisting of a surfactant, an
antioxidant, a slimicide, and an anti-microbial.
10. The process of claim 9, wherein the agent is a surfactant selected from
the group consisting of cationic surfactants, non-ionic surfactants and
combinations
thereof.
11. The process of claim 10, wherein the surfactant is selected from the
group consisting of ethoxylated sorbitans, ethoxylated fatty acids,
polysorbate-80,
glycerol oleate, oleate salts, coconate salts, laurelate salts and
combinations thereof.
12. The process of claim 9, wherein the agent is an anti-microbial selected
from the group consisting of halogenated salicylanilides, halogenated
carbanilides,
alkylbenzoylacrylates, thiuram sulfides, quaternary ammonium compounds,
halogenated anilides of thiophene carboxylic acids, chlorohexidines,
dithiocarbamates, halogenated bisphenols, halogenated diphenyl ethers, and
antibiotics.
13. The process of claim 9, wherein the agent is an anti-microbial selected
from the group consisting of 2-bromo-2-nitropropane-1,3-diol; 1,5-pentanedial;
tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione; and 1,3,5-tris-(2-
hydroxyethyl)-1,3,5-hexahydrotriazine.
14. The process of claim 9, wherein the agent is an antioxidant selected
from the group consisting of alpha-lipoic acid, alpha-tocopherol, alpha-
tocopherol
26

acetate, ascorbic acid, ascorbyl palmitate, beta-propiolactone, BHA, BHT,
carvone,
cinnamaldehyde, citral, decanal, dehydroacetic acid, delta-tocopherol,
diacetyl,
dilauryl thiodipropionate, dodecyl gallate, eugenol, gallic acid, limonene,
octyl gallate,
oregano oil, piperonal, propyl gallate, stearyl citrate, TBHQ, and vanillin.
15. The process of claim 1, wherein the 1,2-dihydroquinoline compound
inhibits microbial growth or replication within the paper product or on the
surface of
the paper product.
16. The process of claim 15, wherein the microbe is selected from the
group consisting of a bacterium, a fungi, a yeast and a virus.
17. The process of claim 16, wherein the microbe is selected from the
group consisting of Pseudomonas, Klebsiella, Enterobacter, Bacillus,
Desulphovibrio, Candida, Saccharomyces, and Aspergillus.
18. The process of claim 1, wherein the paper product is paper or
paperboard.
27

19. A method of inhibiting microbial growth or replication in a paper
product, the method comprising contacting the paper product with a substituted
1,2-
dihydroquinoline compound.
20. The method of claim 19, wherein the substituted 1,2-dihydroquinoline is
a compound having the formula:
<IMG>
wherein:
R1, R2, R3 and R4 are independently selected from the group consisting
of hydrogen and an alkyl group having from 1 to about 6 carbons;
R5 is an alkoxy group having from 1 to about 12 carbons.
21. The method of claim 19, wherein the substituted 1,2-dihydroquinoline
compound is 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline.
22. The method of claim 19, wherein the substituted 1,2-dihydroquinoline is
present in the paper product at a concentration of at least 300 ppm.
23. The method of claim 19, wherein the substituted 1,2-dihydroquinoline is
present in the paper product at a concentration of at least 0.1% by weight.
24. The method of claim 19, wherein the substituted 1,2-dihydroquinoline is
present in the paper product at a concentration from about 0.1% to about 5% by
weight.
28

25. The method of claim 19, further comprising contacting an additional
agent with the paper product, the agent selected from the group consisting of
a
surfactant, an antioxidant, a slimicide, and an anti-microbial.
26. The method of claim 25, wherein the agent is a surfactant selected
from the group consisting of cationic surfactants, non-ionic surfactants and
combinations thereof.
27. The method of claim 26, wherein the surfactant is selected from the
group consisting of ethoxylated sorbitans, ethoxylated fatty acids,
polysorbate-80,
glycerol oleate, oleate salts, coconate salts, laurelate salts and
combinations thereof.
28. The method of claim 25, wherein the agent is an anti-microbial selected
from the group consisting of halogenated salicylanilides, halogenated
carbanilides,
alkylbenzoylacrylates, thiuram sulfides, quaternary ammonium compounds,
halogenated anilides of thiophene carboxylic acids, chlorohexidines,
dithiocarbamates, halogenated bisphenols, halogenated diphenyl ethers, and
antibiotics.
29. The method of claim 25, wherein the agent is an anti-microbial selected
from the group consisting of 2-bromo-2-nitropropane-1,3-diol; 1,5-pentanedial;
tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione; and 1,3,5-tris-(2-
hydroxyethyl)-1,3,5-hexahydrotriazine.
30. The method of claim 25, wherein the agent is an antioxidant selected
from the group consisting of alpha-lipoic acid, alpha-tocopherol, alpha-
tocopherol
acetate, ascorbic acid, ascorbyl palmitate, beta-propiolactone, BHA, BHT,
carvone,
cinnamaldehyde, citral, decanal, dehydroacetic acid, delta-tocopherol,
diacetyl,
dilauryl thiodipropionate, dodecyl gallate, eugenol, gallic acid, limonene,
octyl gallate,
oregano oil, piperonal, propyl gallate, stearyl citrate, TBHQ, and vanillin.
29

31. The method of claim 19, wherein the microbe is selected from the
group consisting of a bacterium, a fungi, a yeast and a virus.
32. The method of claim 19, wherein the microbe is selected from the
group consisting of Pseudomonas, Klebsiella, Enterobacter, Bacillus,
Desulphovibrio, Candida, Saccharomyces, and Aspergillus.
33. The method of claim 19, wherein the paper product is paper or
paperboard.

34. A paper product, the product comprising paper and a substituted 1,2-
dihydroquinoline compound.
35. The paper product of claim 34, wherein the substituted 1,2-
dihydroquinoline compound is disposed on the surface of the paper product.
36. The paper product of claim 34, the paper product having paper fibers
comprising a plurality of interstices, the substituted 1,2-dihydroquinoline
compound
being deposited within the interstices.
37. The paper product of claim 34, wherein the substituted 1,2-
dihydroquinoline is a compound having the formula:
<IMG>
wherein:
R1, R2, R3 and R4 are independently selected from the group consisting
of hydrogen and an alkyl group having from 1 to about 6 carbons;
R5 is an alkoxy group having from 1 to about 12 carbons.
38. The paper product of claim 34, wherein the substituted 1,2-
dihydroquinoline compound is 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline.
39. The paper product of claim 34, wherein the substituted 1,2-
dihydroquinoline is present in the paper product at a concentration of at
least 300
ppm.
31

40. The paper product of claim 34, wherein the substituted 1,2-
dihydroquinoline is present in the paper product at a concentration of at
least 0.1%
by weight.
41. The paper product of claim 34, wherein the substituted 1,2-
dihydroquinoline is present in the paper product at a concentration from about
0.1%
to about 5% by weight.
42. The paper product of claim 34, further comprising an additional agent
selected from the group consisting of a surfactant, an antioxidant, a
slimicide, and an
anti-microbial.
43. The paper product of claim 42, wherein the agent is a surfactant
selected from the group consisting of cationic surfactants, non-ionic
surfactants and
combinations thereof.
44. The paper product of claim 43, wherein the surfactant is selected from
the group consisting of ethoxylated sorbitans, ethoxylated fatty acids,
polysorbate-
80, glycerol oleate, oleate salts, coconate salts, laurelate salts and
combinations
thereof.
45. The paper product of claim 42, wherein the agent is an anti-microbial
selected from the group consisting of halogenated salicylanilides, halogenated
carbanilides, alkylbenzoylacrylates, thiuram sulfides, quaternary ammonium
compounds, halogenated anilides of thiophene carboxylic acids,
chlorohexidines,
dithiocarbamates, halogenated bisphenols, halogenated diphenyl ethers, and
antibiotics.
46. The paper product of claim 45, wherein the agent is an anti-microbial
selected from the group consisting of 2-bromo-2-nitropropane-1,3-diol; 1,5-
pentanedial; tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione; and 1,3,5-
tris-(2-
hydroxyethyl)-1,3,5-hexahydrotriazine.
32

47. The paper product of claim 42, wherein the agent is an antioxidant
selected from the group consisting of alpha-lipoic acid, alpha-tocopherol,
alpha-
tocopherol acetate, ascorbic acid, ascorbyl palmitate, beta-propiolactone,
BHA, BHT,
carvone, cinnamaldehyde, citral, decanal, dehydroacetic acid, delta-
tocopherol,
diacetyl, dilauryl thiodipropionate, dodecyl gallate, eugenol, gallic acid,
limonene,
octyl gallate, oregano oil, piperonal, propyl gallate, stearyl citrate, TBHQ,
and
vanillin.
48. The paper product of claim 34, wherein the 1,2-dihydroquinoline
compound inhibits microbial growth or replication within the paper product or
on the
surface of the paper product.
49. The paper product of claim 48, wherein the microbe is selected from
the group consisting of a bacterium, a fungi, a yeast and a virus.
50. The paper product of claim 48, wherein the microbe is selected from
the group consisting of Pseudomonas, Klebsiella, Enterobacter, Bacillus,
Desulphovibrio, Candida, Saccharomyces, and Aspergillus.
51. The paper product of claim 34, wherein the paper product is paper or
paperboard.
52. A composition comprising a substituted 1,2-dihydroquinoline compound
and pulp or a pulp slurry.
33

Description

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ANTI-MICROBIAL PAPER PRODUCTS HAVING A
SUBSTITUTED 1,2-DIHYDROQUINOLINE
FIELD OF THE INVENTION
[0001] The invention generally provides paper products comprising
antimicrobial agents and processes for making paper products comprising
antimicrobial agents. In particular, the antimicrobial agent typically
comprises a
substituted 1,2-dihydroquinoline compound.
BACKGROUND OF THE INVENTION
[0002] Paper and paper products are attractive sources for the growth
of bacteria, fungi, and molds. Antimicrobial agents have been applied to the
surface
of the paper product after manufacture. If the coating is compromised,
however, the
paper or paper product is not longer protected from microbial growth.
Antimicrobial
agents have also been added to the pulp during the paper making process, such
that
they are incorporated into the finished paper product. Generally, high
concentrations
of an antimicrobial agent must be added during manufacture to obtain
substantial
antimicrobial activity in the finished paper product. The use of high
concentrations of
antimicrobial agents not only increases the cost of manufacture, but may also
introduce waste material that has to be treated before release into waterways,
which
further increases the cost of manufacture. There is a need, therefore, for
alternative
antimicrobial agents to provide protection to paper products. These
antimicrobial
agents should be effective at relatively low doses, should present no health
and
environmental concerns, and should not be cost prohibitive.
SUMMARY OF THE INVENTION
[0003] One aspect of the invention provides a process of producing a
paper product. The process comprises contacting a substituted 1,2-
dihydroquinoline
compound with a composition comprising pulp.
[0004] Yet another aspect of the invention encompasses a method of
inhibiting microbial growth or replication in a paper product. The method
comprises
contacting a paper product with a substituted 1,2-dihydroquinoline compound.
[0005] A further aspect of the invention provides a paper product
comprising paper and a substituted 1,2-dihydroquinoline compound.
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Another aspect of the invention encompasses a composition comprising a
substituted 1,2-dihydroquinoline compound and pulp or pulp slurry.
DETAILED DESCRIPTION OF THE INVENTION
[0006] It has been discovered that substituted 1,2-dihydroquinoline
compounds function as anti-microbial agents when contacted with a paper
product or
when contacted with raw materials used in paper manufacturing. In a typical
embodiment of the invention, the compound may be added during the paper
manufacturing process, such as to pulp or pulp slurry, to inhibit microbial
growth or
replication in the paper manufacturing raw materials. Alternatively, the
compound
may be disposed within, on the surface, or within and on the surface of a
paper
product to inhibit microbial growth or replication on the paper product. The
substituted 1,2-dihydroquinoline, when added to a paper product in an
effective
amount as illustrated in the examples, inhibits microbial growth and/or
replication
that could otherwise destroy the paper product or be harmful to the user of
the paper
product. Advantageously, the substituted 1,2-dihydroquinoline compounds also
function as antioxidants, reducing oxidation of the paper product. Moreover,
the
substituted 1,2-dihydroquinolines are thermally stable at temperatures
employed,
and unlike some of the existing mold proofing agents used by the paper
industry,
they do not decompose or undergo the reaction of pyrolysis during paper and
pulp
processing, for example, drying and in a preferred embodiment; the compounds
do
not cause discoloration of the paper products.
I. Paper Products Having Substituted 1,2-Dihydroquinoline Compounds
[0007] One aspect of the present invention provides paper products
having substituted 1,2-dihydroquinoline compounds. Substituted 1,2-
dihydroquinoline compounds suitable for use in the invention generally
correspond to
formula (I):
R4
R R3
R2
N R'
H
2

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(I)
wherein:
R1, R2, R3 and R4 are independently selected from the group
consisting of hydrogen and an alkyl group having from 1 to about 6
carbons;
R5 is an alkoxy group having from 1 to about 12 carbons.
[0008] In another embodiment, the substituted 1,2-dihydroquinoline will
have formula (I) wherein:
R1, R2, R3 and R4 are independently selected from the group
consisting of hydrogen and an alkyl group having from 1 to about 4
carbons; and
R5 is an alkoxy group having from 1 to about 4 carbons.
[0009] In one preferred embodiment, the substituted 1,2-
dihydroquinoline will be 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline having
the
formula:
H
N
6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline, commonly known as ethoxyquin,
is
sold under the trademark SANTOQUIN . The present invention also encompasses
salts of ethoxyquin and other compounds having formula (I). Ethoxyquin and
other
compounds having formula (I) may be purchased commercially from Novus
International, Inc. or made in accordance with methods generally known in the
art,
for example, as detailed in U.S. Patent No. 4,772,710, which is hereby
incorporated
by reference in its entirety.
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[0010] Typically, in each embodiment described herein, the substituted
1,2-dihydroquinoline compound may be formulated as a liquid, powder or
emulsion
and contacted with the paper product. A suitable example of an emulsion
formulation comprises approximately 70% by weight 6-ethoxy-1,2-dihydro-2,2,4-
trimethylquinoline, approximately 23% by weight water, approximately 5% by
weight
Tween and approximately 2% by weight myverol 18-19.
[0011] As will be appreciated by a skilled artisan, the technique for
contacting the substituted 1,2-dihydroquinoline compound with the paper
product
can and will vary, depending upon the paper product and its manufacturing
process.
In one embodiment, the substituted 1,2-dihydroquinoline compounds may be
incorporated into the paper product during its original manufacture. According
to one
alternative of this embodiment, the substituted 1,2-dihydroquinoline is
typically
contacted with at least one raw material in the paper manufacturing process,
such as
pulp or a mixture of pulp and water ("pulp slurry") to minimize spoilage of
the paper,
pulp or pulp slurry. Depending upon the embodiment, the pulp may be produced
from a chemical pulping method or from a mechanical pulping method. The paper
product of the invention is formed from the pulp slurry by extracting water
from the
slurry to form a paper web comprising paper fibers having interstices. Water
may be
removed from the pulp slurry according to generally known methods, for
example, by
applying negative pressure (vacuum) or heat.
[0012] In another embodiment, the substituted 1,2-dihydroquinoline
compounds may be contacted with the paper product contemporaneously as the
interstices are formed. In this embodiment, the paper web having interstices
may be
passed through a size press, according to methods known in the art. The size
press
will typically comprise two squeeze rollers between which the paper web is
passed.
As a part of the process, a composition comprising a substituted 1,2-
dihydroquinoline compound and water or another suitable aqueous carrier, is
dispensed, for example, through hoses emanating from one or more tanks and
directed between the squeeze rollers. The squeeze rollers generally have a gap
between them that defines the thickness of the paper web. As such, by setting
the
gap to a size equal to or smaller as compared to the thickness of the paper
web, the
substituted 1,2-dihydroquinoline compound may be forced into the interstices
of the
paper fibers. Penetration and distribution of the substituted 1,2-
dihydroquinoline
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compound is achieved throughout a substantial portion of the thickness of the
paper.
After passing the paper web through the sizing press, the paper web
incorporated
with the substituted 1,2-dihydroquinoline compound, may be passed over a
heated
drying drum to evaporate the remaining water. The paper product is then ready
for
production into a variety of products, as described in detail below.
[0013] Alternatively, the substituted 1,2-dihydroquinoline compound
may be contacted with the paper product after its manufacture. For example,
the
paper product may be lightly dampened with a solution comprising the
substituted
1,2-dihydroquinoline compound, and then allowed to dry. Typically, this
process
leaves the substituted 1,2-dihydroquinoline compound disposed on the surface
of the
paper product.
[0014] Irrespective of when the substituted 1,2-dihydroquinoline
compound is added in the paper manufacturing process, it is typically added to
the
paper product in an anti-microbial effective amount. The amount of substituted
1,2-
dihydroquinoline that constitutes an "anti-microbial effective amount" can and
will
vary depending upon several factors, such as, the type of paper product, the
microbial target, and the degree of anti-microbial activity desired. Generally
speaking when the substituted 1,2-dihydroquinoline is disposed within or on
the
surface of the paper product, as illustrated in the examples, an effective
amount is a
concentration of at least 250 ppm and more typically, at least 300 ppm. In
another
embodiment, the substituted 1,2-dihydroquinoline compound is added to the
paper
product at a concentration from about 250 ppm to about 1000 ppm. In another
embodiment, the substituted 1,2-dihydroquinoline compound is added to the
paper
product at a concentration from about 400 ppm to about 600 'ppm. Stated
another
way, the substituted 1,2-dihydroquinoline compound is typically added to the
paper
product at a concentration of at least 0.1% by weight. In a further
embodiment, the
substituted 1,2-dihydroquinoline compound is added at a concentration from
about
0.1 % to about 5% by weight. Alternatively, when the substituted 1,2-
dihydroquinoline is added to a raw material during the paper manufacturing
process,
typically it is added at a concentration of about 50 ppm to about 6000 ppm.
[0015] A variety of paper products are encompassed by the present
invention, including paper and paperboard. The paper product may be used to
store
and communicate information. For example, the paper product may be newsprint,

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magazine paper, book paper, printing paper or writing paper. The paper product
may be used to transport and protect food, such as, packaging, sacks, tetra
packs,
paper towels, and paper plates and cups. Alternatively, the paper product may
be
used for personal hygiene. For example, the paper product may be tissues,
toilet
paper, feminine products, and diapers. The paper product may be used for
packaging materials and products. In this application, the paper may be
paperboard
used in the manufacture of corrugated board, folding boxboard, and wrapping.
The
paper product may be used to make specialized papers, such as, monetary
currency, cigarette papers and filter papers, as well as gypsum liners and
special
papers for waxing, insulating, roofing, and asphalting.
[0016] The previous discussion has focused on paper products, but the
invention can also be used with similar materials having non-wood based fiber
construction. For example, the substituted 1,2-dihydroquinoline may be
contacted
with several types of non-wood fibers to inhibit microbial growth and/or
replication.
Non-wood fibers can include fibers woven and nonwoven from wood, plants and/or
other textile fibers including but not limited to Aramid (Nomex/Keviar)
Conductive
Nylon (Polyolefin), Nylon (Bi-component side by side sheath core), Cotton,
Rayon,
Wool, Local and Modacrylic (Fusible co-Pet fiber) ground to its individual
constituents or treated chemically, by digestion with acidic or basic liquors,
to form
Cellulose, the main fibrous component most suited for making paper goods. It
will
be apparent to those skilled in the art that impregnating a fibrous material,
particularly a fibrous sheet material such as paper, will allow for the
antimicrobial
properties of the impregnating material to be added to the physical properties
of the
fibrous material.
ll. Additional Agents
[0017] Another aspect of the invention comprises a paper product
having a substituted 1,2-dihydroquinoline compound and at least one additional
agent. Typically, the agent is selected from the group consisting of a
surfactant, an
anti-microbial, an antioxidant, a slimicide, and a protected or
microencapsulated 2-
hydroxy-4-methylthiobutanoic acid, i.e., hydroxy analog of methionine. The
agent
may be contacted with the paper product contemporaneously with the substituted
1,2-dihydroquinoline compound. Alternatively, the agent may be contacted with
the
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paper product either before or after the substituted 1,2-dihydroquinoline
compound is
contacted with the paper product. The agent may be contacted with the paper
product during its manufacture or after its manufacture according to any
method
known in the art or as detailed herein.
(a) surfactants
[0018] Suitable surfactants for use in combination with the substituted
1,2-dihydroquinoline compound include cationic surfactants, non-ionic
surfactants
and combinations thereof. For example, the surfactant may be selected from the
group consisting of ethoxylated sorbitans, ethoxylated fatty acids,
polysorbate-80,
glycerol oleate, oleate salts, coconate salts, laurelate salts and
combinations thereof.
Suitable combinations of a substituted 1,2-dihydroquinoline compound and a
surfactant are illustrated in Table A.
TABLE A
First Compound Second Compound
Ethox quin ethoxylated sorbitans
Ethoxyguin ethoxylated fatty acids
Ethox uin polysorbate-80
Ethoxyguin glycerol oleate
Ethox uin oleate salts
Ethoxyguin coconate salts
Ethoxyguin laurelate salts
Ethoxyguin combinations thereof
(b) anti-microbial agents
[0019] Several anti-microbial agents are suitable for use in combination
with the substituted 1,2-dihydroquinoline compound. Typically the anti-
microbial
agent selected is an agent that acts synergistically with the anti-microbial
activity of
the substituted 1,2-dihydroquinoline compound. In this context,
"synergistically"
includes not only those anti-microbial agents that enhance the anti-microbial
activity
of the substituted 1,2-dihydroquinoline compound, but also anti-microbial
agents that
inhibit at least one or more microbes of a different spectrum. In one
embodiment,
the anti-microbial agent is selected from the group consisting of halogenated
salicylanilides, halogenated carbanilides, alkylbenzoylacrylates, thiuram
sulfides,
quaternary ammonium compounds, halogenated anilides of thiophene carboxylic
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acids, chlorohexidines, dithiocarbamates, halogenated bisphenols, halogenated
diphenyl ethers, and antibiotics. Examples of suitable halogenated
salicylanilides
include: 5-bromo-salicylanilide; 4',5-dibromo-salicylanilide; 3,4',5-tribromo-
salicylanilide; 6-chloro-salicylanilide; 4'5-dichloro-salicylanilide; 3,4'5-
trichloro-
salicylanilide; 4',5-diiodo-salicylanilide; 3,4',5-triiodo-salicylanilide; 5-
chloro-3'-
trifluoromethyl-salicylanilide; 5-chloro-2'-trifluoromethyl-salicylanilide;
3,5-dibromo-3'-
trifluoromethyl-salicylanilide; 3-chloro-4-bromo-4'-trifluoromethyl-
salicylanilide; 2',5-
dichloro-3-phenyl-salicylanilide; 3',5-dichloro-4'-methyl-3-phenyl-
salicylanilide; 3',5-
dichloro-4'phenyl-3-phenyl-salicylanilide; 3,3',5-trichloro-6'-(p-
chlorophenoxy)-
salicylanilide; 3',5-dichloro-5'-(p-bromophenoxy)-salicylanilide; 3,5-dichloro-
6'-
phenoxy-salicylanilide; 3,5-dichloro-6'-(o-chlorophenoxy)-salicylanilide; 5-
chloro-6'-
(o-chlorophenoxy)-salicylanilide; 5-chloro-6'-beta-naphthyloxy-salicylanilide;
5-chloro-6'-alpha-naphthyloxy-salicylanilide; and 3,3',4-trichloro-5,6'-beta-
naphthyloxy-salicylanilide. By way of non-limiting example, suitable
halogenated
carbanilides include: 3,4,4'-trichloro-carvanilide, the 3,3',4-trichloro
derivatives, and
3-trifluoromethyl-4,4'-dichlorocarbanilide. Examples of suitable bis-phenols
are
represented by the following: 2,2'-methylenebis(4-chlorophenol);2,2'-
methylenebis(4,5-dichlorophenol); 2,2'-methylenebis(3,4,6-trichlorophenol);
2,2'-
thiobis(4,6-dichlorophenol); 2,2'-diketobis(4-bromophenol); 2,2'-
methylenebis(4-
chloro-6-isopropylphenol); and2,2'-isopropylidenebis(6-sec-butyl-4-
chlorophenol).
Examples of suitable quaternary ammonium compounds are:
diisobutylphenoxyethoxyethyidimethylbenzylammonium chloride;
N-methyl-N-(2-hydroxyethyl)-N-(2-hydroxydodecyl)-N-benzyl ammonium chloride;
Cetyl trimethylammonium bromide; Stearyl trimethylammonium bromide; Oleyl
dimethylethylammonium bromide; Lauryidimethylchlorethoxyethylammonium
chloride; Luryidimethylchlorethoxyethylammonium chloride; Alkyl(C8-
C18)dimethyl(3,4-dichlorobenzyl)-ammonium chloride; Lauryl pyridinium bromide;
Lauryl isoquinolinium bromide; and
N(lauroyloxyethylaminoformylnethyl)pyridinium
chloride. Examples of suitable thiocarbamates and the thiuram sulfides
include:
Dsodium ethylene bis-dithiocarbamate (Nabam); Dammonium ethylene bis-
dithiocarbamate(amabam); Zn ethylene bis-dithiocarbamate (ziram); Fe ethylene
bis-
dithiocarbamate (ferbam); Mn ethylene bis-dithiocarbamate (manzate); Tramethyl
thiuram disulfide; Ttrabenzyl thiuram disulfide; Ttraethyl thiura, disulfide;
and
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Ttramethyl thiuram sulfide. In another embodiment, the anti-microbial agent is
selected from the group consisting of 2-bromo-2-nitropropane-1,3-diol (sold
under
the trademark Myacide AS); 1,5-pentanedial (sold under the trademark
Protectol
GA 50); tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione (sold under the
trademark Protectol DZ; and 1,3,5-tris-(2-hydroxyethyl)-1,3,5-
hexahydrotriazine
(sold under the trademark Protectol HT). Suitable combinations of a
substituted
1,2-dihydroquinoline compound and an additional anti-microbial agent are
illustrated
in Table B.
TABLE B
First Compound Second Compound
substituted 1,2- halogenated salicylanilides
dihydroquinoline
compound
substituted 1,2- halogenated carbanilides
dihydroquinoline
compound
substituted 1,2- alkylbenzoylacrylates
dihydroquinoline
compound
substituted 1,2- thiuram sulfides
dihydroquinoline
compound
substituted 1,2- quaternary ammonium compounds
dihydroquinoline
compound
substituted 1,2- halogenated anilides of thiophene carboxylic acids
dihydroquinoline
compound
substituted 1,2- chlorohexidines
dihydroquinoline
compound
substituted 1,2- dithiocarbamates
dihydroquinoline
compound
substituted 1,2- halogenated bisphenols
dihydroquinoline
compound
substituted 1,2- halogenated diphenyl ethers
dihydroquinoline
com ound
substituted 1,2- antibiotics
dihydroquinoline
compound
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Ethoxyguin 5-bromo-salicylanilide
Ethoxyguin 4',5-dibromo-salicylanilide
Ethoxyguin 3,4',5-tribromo-salicylanilide
Ethoxyguin 6-chloro-salic lanilide
Ethoxyquin 4'5-dichloro-salicylanilide
Ethoxyquin 3,4'5-trichloro-salicylanilide
Ethoxyguin 4',5-diiodo-salic lanilide
Ethoxyguin 3,4',5-triiodo-salicylanilide
Ethoxyquin 5-chloro-3'-trifluorometh I-salic lanilide
Ethoxyguin 5-chloro-2'-trifluorometh I-salic lanilide
Ethoxyguin 3,5-dibromo-3'-trifluorometh I-salic lanilide
Ethox uin 3-chloro-4-bromo-4'-trifluorometh I-salic lanilide
Ethox uin 2',5-dichloro-3- hen I-salic lanilide
Ethox uin 3',5-dichloro-4'-meth I-3- hen I-salic lanilide
Ethox uin 3',5-dichloro-4' hen I-3- hen I-salic lanilide
Ethox uin 3,3',5-trichloro-6'- -chloro henox -salic lanilide
Ethox uin 3',5-dichloro-5'- -bromo henox -salic lanilide
Ethox uin 3,5-dichloro-6'- henox -salic lanilide
Ethox quin 3,5-dichloro-6'- o-chloro henox -salic lanilide
Ethox uin 5-chloro-6'- o-chloro henox -salic lanilide
Ethox uin 5-chloro-6'-beta-na hth lox -salic lanilide
Ethox uin 5-chloro-6'-aI ha-na hth lox -salic lanilide
Ethox uin 3,3',4-trichloro-5,6'-beta-na hth lox -salic lanilide
Ethox uin 3,4,4'-trichloro-carvanilide
Ethoxyquin 3,3',4-trichloro derivatives
Ethox uin 3-trifluoromethyl-4,4'-dichlorocarbanilide
Ethoxyguin 2,2'-meth lenebis 4-chloro henol
Ethox uin 2,2'-meth lenebis 4,5-dichloro henol
Ethoxyquin 2,2'-meth lenebis 3,4,6-trichloro henol
Ethoxyguin 2,2'-thiobis 4,6-dichloro henol
Ethox uin 2,2'-diketobis 4-bromo henol
Ethoxyguin 2,2'-meth lenebis 4-chloro-6-iso ro I phenol)
Ethox uin 2,2'-iso ro lidenebis 6-sec-but I-4-chloro henol
Ethoxyquin diisobutylphenoxyethoxyethyidimethylbenzylammonium
chloride
Ethoxyq ui n N-methyl-N-(2-hyd roxyethyl )-N-(2-hyd roxydod ecyl )-N-
benz I ammonium chloride
Ethox uin Cetyl trimethylammonium bromide
Ethoxyquin Stearyl trimethylammonium bromide
Ethoxyquin Oleyl dimethylethylammonium bromide
Ethox uin Laur idimeth Ichlorethox eth lammonium chloride
Ethox uin Lur idimeth Ichlorethox eth lammonium chloride
Ethoxyquin Alkyl(C8-C18)dimethyl(3,4-dichlorobenzyl)-ammonium
chloride
Ethox uin Lauryl pyridinium bromide
Ethoxyguin Lauryl iso uinolinium bromide
Ethoxyquin N lauro loxyeth laminoform Ineth I p ridinium chloride

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Ethoxyguin Dsodium ethylene bis-dithiocarbamate (Nabam)
Ethoxyguin Dammonium ethylene bis-dithiocarbamate amabam
Ethoxyguin Zn ethylene bis-dithiocarbamate (ziram)
Ethoxyguin Fe ethylene bis-dithiocarbamate (ferbam)
Ethoxyguin Mn ethylene bis-dithiocarbamate (manzate)
Ethoxyquin Tramethyl thiuram disulfide
Ethoxyguin Ttrabenzyl thiuram disulfide
Ethoxyquin Ttraethyl thiura, disulfide
Ethox uin Ttramethyl thiuram sulfide
Ethoxyquin 2-bromo-2-nitropropane-1,3-diol (sold under the
trademark M acide AS)
Ethoxyquin 1,5-pentanedial (sold under the trademark Protectol
GA 50)
Ethoxyquin tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2-thione
(sold under the trademark Protectol DZ)
Ethoxyq uin 1, 3, 5-tris-(2-hyd roxyethyl )-1, 3, 5-hexahyd rotriazi ne
(sold under the trademark Protectol HT)
(c) antioxidants
[0020] Several antioxidant agents are suitable for use in combination
with the substituted 1,2-dihydroquinoline compound. Suitable antioxidant
agents are
typically included to reduce degradation or deterioration of the paper
product. For
example, the antioxidant may be selected from the group consisting of trialkyl
phosphites, mixed alkyl/aryl phosphites, alkylated aryl phosphites, sterically
hindered
aryl phosphites, aliphatic spirocyclic phosphites, sterically hindered phenyl
spirocyclics, sterically hindered bisphosphonites, hydroxyphenyl propionates,
hydroxy benzyls, alkylidene bisphenols, alkyl phenols, aromatic amines,
thioethers,
hindered amines, hydroquinones and mixtures thereof. Alternatively, the
antioxidant
may be any of the antioxidants delineated in the Examples, such as, alpha-
lipoic
acid, alpha-tocopherol, alpha-tocopherol acetate, ascorbic acid, ascorbyl
palmitate,
beta-propiolactone, BHA, BHT, carvone, cinnamaldehyde, citral, decanal,
dehydroacetic acid, delta-tocopherol, diacetyl, dilauryl thiodipropionate,
dodecyl
gallate, eugenol, gallic acid, limonene, octyl gallate, oregano oil,
piperonal, propyl
gallate, stearyl citrate, TBHQ, and vanillin. Suitable combinations of a
substituted
1,2-dihydroquinoline compound and an additional antioxidant are illustrated in
Table
C.
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TABLE C
First Compound Second Compound
substituted 1,2-dihydroquinoline trialkyl phosphites
compound
substituted 1,2-dihydroquinoline mixed alkyl/aryl phosphites
com ound
substituted 1,2-dihydroquinoline alkylated aryl phosphites
compound
substituted 1,2-dihydroquinoline sterically hindered aryl
com ound
substituted 1,2-dihydroquinoline phosphites aliphatic spirocyclic
compound phosphites
substituted 1,2-dihydroquinoline sterically hindered phenyl spirocyclics
compound
substituted 1,2-dihydroquinoline sterically hindered bisphosphonites
com ound
substituted 1,2-dihydroquinoline hydroxyphenyl propionates
compound
substituted 1,2-dihydroquinoline hydroxy benzyls
compound
substituted 1,2-dihydroquinoline alkylidene bisphenols
compound
substituted 1,2-dihydroquinoline alkyl phenols
com ound
substituted 1,2-dihydroquinoline aromatic amines
compound
substituted 1,2-dihydroquinoline thioethers
compound
substituted 1,2-dihydroquinoline hindered amines
compound
substituted 1,2-dihydroquinoline Hydroquinones
compound
Ethox uin al ha-li oic acid
Ethoxyguin al ha-toco herol
Ethoxyguin al ha-toco herol acetate
Ethoxyguin ascorbic acid
Ethoxyguin ascorbyl palmitate
Ethox uin beta- ro iolactone
Ethoxyguin BHA
Ethoxyguin BHT
Ethoxyguin carvone
Ethox quin Cinnamaldehyde
Ethox uin citral
Ethox uin decanal
Ethox uin dehydroacetic acid
Ethox uin delta-tocopherol
Ethoxyquin diacetyl
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Ethoxyguin dilauryl thiodi ro ionate
Ethoxyguin dodecyl gailate
Ethoxyguin eugenol
Ethoxyguin gallic acid
Ethoxyguin limonene
Ethoxyquin octyl gallate
Ethox uin oregano oil
Ethoxyguin piperonal
Ethoxyguin propyl gallate
Ethoxyquin stearyl citrate
Ethoxyguin TBHQ
Ethoxyquin vanillin
[0021] As will be appreciated by the skilled artisan, any of the
surfactants, anti-microbials, or antioxidants may be combined, either alone or
in
combination with one another, with the substituted 1,2-dihydroquinoline to
form a
composition of the invention. The concentration of these agents will depend
upon the
application but, in general, will be between about 0.0001 % and about 10% by
weight
of the paper product, more preferably between about 0.001 % and about 7.5%,
most
preferably between about 0.01 lo and about 5%.
(d) slimicides
[0022] A variety of slimicides are suitable for use in combination with
the substituted 1,2-dihydroquinoline compound. Suitable examples of slimicides
include Acticide DW, HF, SPX (from Thor, Inc. known under the isothiazolin
family
of products such as DCOIT, BIT, CIT etc.); Dantochlor and Dantobrom PG
granular of briquette from Lonza, Inc. (known as halogenated hydantoin, e.g.,
1-
bromo-3-chloro-5,5-dimethylhydantoin and/or 1,3-dichloro 5,5 dimethyl
hydantoin
and/or 1,3-dichloro-5-ethyl-5methyl hydantoin); Paxgard BD20, BD88, BKC, EM,
MBT from Pax Chem, Inc. (known as 2-bromo-2-nitropropane-1,3 diol, alkyl
dimethyl
benzyl ammonium chloride, hexahydro-1,3,5-tris (2-hydroxyethyl)-s-triazine,
methylenebisisothiocyanate etc); Paxgard BSL, BU 30L, BU 30, BU 60, MB 10, TC
;
Busan 1223 from Buckmann Lab.; Metasol CB-220, CB-225AD, CB-225 L.C, CMI-
150 from Ondeo-Nalco, Inc. (known as tripropyleneglycol monomethyl ether (80%)
and 1,2 dibromo 2,4-dicyanobutane (20%), (25%), CMIT and MIT at 1.15% and
0.35% respectively). Generally, the ratio of substituted 1,2-dihydroquinoline
to any
of the slimicides referenced herein can and will vary. By way of non-limiting
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example, the ratio 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline to slimicide
may
vary from 0.05 to 99% by weight. Suitable combinations of a substituted 1,2-
dihydroquinoline compound and a slimicide are illustrated in Table D.
TABLE D
First Compound Second Compound
Ethoxyguin Acticide
Ethox uin DantochlorR
Ethox uin Dantobrom
Ethoxyquin 1 -brom o-3-chl oro-5,5-d i m ethyl hyd antoi n
Ethoxyguin 1,3-dichloro 5,5 dimethyl hydantoin
Ethoxyguin 1,3-dichloro-5-eth I-5meth I h dantoin
Ethoxyquin 2-bromo-2-nitropropane-1,3 diol, alkyl
dimethyl benzyl ammonium chloride
Ethoxyquin hexahydro-1,3,5-tris (2-hydroxyethyl)-s-
triazine
Ethox uin meth lenebisisothioc anate
Ethox uin tri rop lene I col monomethyl ether
(e) hydroxyl analog of inethionine
[0023] The substituted 1,2-dihydroquinoline compound may be
combined with a protected or microencapsulated 2-hydroxy 4-methylthio butanoic
acid (HMTBA), i.e., hydroxyl analog of methionine. Suitable hydroxyl analogs
of
methionine include 2-hydroxy-4(methylthio)butanoic acid (sold by Novus
International, St. Louis, Mo under the trade name Alimet ), its salts, esters,
amides,
and oligomers. Representative salts of HMTBA include the ammonium salt, the
stoichiometric and hyperstoichiometric alkaline earth metal salts (e.g.,
magnesium
and calcium), the stoichiometric and hyperstoichiometric alkali metal salts
(e.g.,
lithium, sodium, and potassium), and the stoichiometric and
hyperstoichiometric zinc
salt. Representative esters of HMTBA include the methyl, ethyl, 2-propyl,
butyl, and
3-methylbutyl esters of HMTBA. Representative amides of HMTBA include
methylamide, dimethylamide, ethylmethylamide, butylamide, dibutylamide, and
butylmethylamide. Representative oligomers of HMTBA include its dimers,
trimers,
tetramers and oligomers that include a greater number of repeating units.
[0024] Alternatively, the hydroxy analog of methionine may be a metal
chelate comprising one or more ligand compounds comprising HMTBA together with
one or more metal ions. Irrespective of the embodiment, suitable non-limiting
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examples of metal ions include zinc ions, copper ions, manganese ions, iron
ions,
chromium ions, cobalt ions, and calcium ions. In one embodiment, the metal ion
is
divalent. Examples of divalent metal ions (i.e., ions having a net charge of
+2)
include copper ions, manganese ions, chromium ions, calcium ions, cobalt ions
and
iron ions. In another embodiment, the metal ion is zinc. In yet another
embodiment,
the metal ion is copper. In still another embodiment, the metal ion is
manganese. In
one exemplary embodiment, the metal chelate is HMTBA-Mn. In a further
exemplary
embodiment, the metal chelate is HMTBA-Cu. In an alternative exemplary
embodiment, the metal chelate is HMTBA-Zn.
[0025] As will be appreciated by a skilled artisan, the ratio of ligands to
metal ions forming a metal chelate compound can and will vary. Generally
speaking,
a suitable ratio of ligand to metal ion is from about 1:1 to about 3:1 or
higher. In
another embodiment, the ratio of ligand to metal ion is from about 1.5:1 to
about
2.5:1. Of course within a given mixture of metal chelate compounds, the
mixture will
include compounds having different ratios of ligand to metal ion. For example,
a
composition of metal chelate compounds may have species with ratios of ligand
to
metal ion that include 1:1, 1.5:1, 2:1, 2.5:1, and 3:1. Metal chelate
compounds of the
invention may be made in accordance with methods generally known in the art,
such
as described in U.S. Patent Nos. 4,335,257 and 4,579,962, which are both
hereby
incorporated by reference in their entirety.
[0026] Suitable combinations of a substituted 1,2-dihydroquinoline
compound and HMTBA are illustrated in Table E.
TABLE E
First Compound Second Compound
substituted 1,2-dihydroquinoline HMTBA
compound
substituted 1,2-dihydroquinoline HMTBA-Cu
compound
substituted 1,2-dihydroquinoline HMTBA-Zn
compound
substituted 1,2-dihydroquinoline HMTBA-Mn
compound
Ethoxyguin HMTBA
Ethoxyguin HMTBA-Cu
Ethoxyguin HMTBA-Zn
Ethoxyquin HMTBA-Mn

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[0027] In one preferred embodiment, as detailed above, the HMTBA is
HMTBA-Cu. A preferred composition comprises from about 30% to about 40% by
weight 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline, from about 1% to about
5% by
weight HMTBA-Cu, and from about 55% to about 65% propylene glycol. In a more
preferred embodiment, the composition comprises about 37% by weight 6-ethoxy-
1,2-dihydro-2,2,4-trimethylquinoline, about 2% by weight HMTBA-Cu, and about
60% by weight propylene glycol.
DEFINITIONS
[0028] "Anti-microbial" is an agent that prevents or inhibits the growth,
replication or growth and replication of a microorganism.
[0029] "Microbial" or "microbe" is used in its broadest sense to
encompass several diverse types of microorganisms, such as, fungi, yeast,
bacteria,
virus, and mildew, that grow and/or replicate during paper manufacturing or on
the
finished paper product. Generally, aerobic slime-forming bacteria, such as,
Pseudomonas, Klebsiella, Enterobacter and Bacillus, are problematic during the
paper manufacturing process. Problematic anerobic microorganisms include
Desulphovibrio. In addition, problematic yeast and fungi include Candida,
Saccharomyces, and Aspergillus.
[0030] "Paper" is used in its broadest sense to encompass a substance
composed of fibers interlaced into a compact web, which can be macerated into
pulp, dried and pressed.
[0031] PPM stands for parts per million.
EXAMPLES
[0032] Examples 1 and 2 demonstrate the ability of a composition
comprising ethoxyquin to inhibit microbial growth on paper products. Example 3
demonstrates the antimicrobial properties of antioxidants and other agents.
[0033] Several of the compounds detailed in Table 1, 2, and 3
presented below are commercially available from Novus International, Saint
Louis,
Missouri (i.e., the composition abbreviated Santoquin is ethoxyquin, Biox AUSD
is a
blend of organic acid, inorganic acid and HMTBA and is sold under the trade
name
ACTIVATE US WD; the compound abbreviated is HMBTA-Cu and is sold under the
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trade name MINTREX Cu; and the compound abbreviated Tox-Guard dry is an
antioxidant blend sold under the trade name TOXGUARD).
Example 1. Fungal Resistance Testing of Several Biocides
[0034] Five different biocides at varying concentrations were tested for
fungal resistance using the ASTM D 2020 Standard Test Method for Mildew
(Fungus) Resistance of Paper and Paperboard protocol. This test method was
designed for the qualitative determination of mildew (fungus) resistance of
paper and
paperboard, particularly those types that have been given a fungus resistant
treatment. Specific test conditions applied to this project are described
below, but at
all times the ASTM D 2020 test protocol was strictly followed.
[0035] All five biocides (Santoquin , HMTBA-Cu, BIOX-AUSD, Tox-
Guard*Dry, and Metasol-TK 100) were tested at three different concentrations
(200,
400, and 600 ppm). Santoquin , HMTBA-Cu, and BIOX-AUSD were diluted in
dimethyl sulfoxide (DMSO), while Tox-Guard*Dry and Metasol-TK100 were diluted
in
water. DMSO was used a control diluent. The fungal inoculum was comprised of
three different species: Aspergillus niger ATCC 9642, Aspergillus flavus ATCC
9643,
and Chaetomium globosum ATCC 6205.
[0036] Glass fiber filter paper was treated with the individual test
biocides at the respective concentrations listed in Table 1 and allowed to dry
overnight. The filter paper carriers, tested in triplicate, were placed in
Petri dishes on
mineral salts agar and inoculated with the fungal inoculum. The samples were
incubated at 28 C for 2 weeks and examined daily during the first week of
incubation
for the growth of the test organisms.
[0037] If a sample showed growth of test organisms after seven days of
incubation, the test was discontinued and the sample was reported as fungus
non-
resistant. If no growth was observed on a sample after the first week of
incubation,
the sample was incubated for an additional seven days. If, after two weeks,
the
sample showed growth of the test fungi, the sample was considered fungus non-
resistant. If, after two weeks, there was no detectable growth of test
organisms, the
sample was considered fungus resistant.
[0038] As delineated in Table 1, the samples treated with Metasol-TK
100 showed no growth at the end of the two weeks. Therefore, the Metasol -TK
100
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treated samples were found to be fungal resistant in the ASTM D 2020 test at
all
three concentrations (200, 400, and 600 ppm). Similarly, the samples treated
with
400 and 600 ppm Santoquin showed no fungal growth at the end of two weeks.
Therefore, the Santoquin treated samples were found to be fungal resistant at
400
and 600 ppm. Comparatively, all concentrations of Tox-Guard*Dry, all
concentrations of BIOX-AUSD, all concentrations of HMTBA-Cu, and Santoquin at
200 ppm showed fungal growth, and therefore these samples were labeled fungus
non-resistant.
Example 2. Fungal Resistance Testing of Santoguin
[0039] One biocide sample, labeled Santoquin was tested for fungal
resistance using the ASTM D 2020 Standard Test Method for Mildew (Fungus)
Resistance of Paper and Paperboard protocol. This test method was designed for
the qualitative determination of mildew (fungus) resistance of paper and
paperboard,
particularly those types that have been given a fungus resistant treatment.
Specific
test conditions applied to this project are described below, but at all times
the ASTM
D 2020 test protocol was strictly followed.
[0040] The Santoquin biocide was diluted with DMSO and tested at
two different concentrations: 0.1 % and 1.0%. The biocide Kathon 893 was
diluted to
0.1 % and 1.0% in water and used as a control biocide. DMSO was used as a
control
diluent. The fungal inoculum was comprised of three different species:
Aspergillus
niger ATCC 9642, Aspergillus flavus ATCC 9643, and Chaetomium globosum ATCC
6205.
[0041] Glass fiber filter paper was treated with two different
concentrations (0.1 % and 1.0%) of Santoquin and allowed to dry overnight.
The
filter paper carriers, tested in triplicate, were placed in Petri dishes on
mineral salts
agar and inoculated with the fungal inoculum. The samples were incubated at 28
C
for 2 weeks and examined daily during the first week of incubation for the
growth of
the test organisms.
[0042] If a sample showed growth of test organisms after seven days of
incubation, the test was discontinued and the sample was reported as fungus
non-
resistant. If no growth was observed on a sample after the first week of
incubation,
the sample was incubated for an additional seven days. If, after two weeks,
the
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sample showed growth of the test fungi, the sample was considered fungus non-
resistant. If, after two weeks, there was no detectable growth of test
organisms, the
sample was considered fungus resistant.
[0043] As delineated in Table 2, the samples treated with Santoquin
showed no fungal growth at the end of the two weeks. Therefore, the Santoquin
treated samples were found to be fungal resistant in the ASTM D 2020 test at
both
concentrations (0.1 % and 1.0%) tested. Comparatively, both concentrations of
Kathon 893 and the control diluent showed fungal growth and therefore these
samples were labeled non-fungus resistant.
Example 3. Fungal Resistance Testing of Other Agents
[0044] The antifungal properties of other agents were tested using an in
vitro disk assay (Higgins and Brinkhaus, 1999, J. Appl. Poultry Res. 8:480-
487). In
this assay, paper disks were soaked in a fungal solution and placed on the
surface of
agar plates containing different concentration of the test agent. The radius
of fungal
growth radiating from each disk was considered indicative of the degree of
inhibition
by the agent relative to a control.
[0045] The test agents were diluted in DMSO or water and tested at
several different concentrations. The test agents were added to the agar
solution
after sterilization, but prior to solidification. Sterile paper disks were
soaked in a
suspension of Aspergillus niger ATCC 9642 and Aspergillus flavus ATCC 9643 and
placed on the agar plates. The plates were incubated for 48 hours at 25 C. The
zones of fungal growth (or no growth) were analyzed and the minimum total
inhibitory concentration (%) was estimated for each agent. Table 3 presents
the
minimum inhibitory concentration of each agent, in ranked order.
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Table 1. Biocide Performance in ASTM D 2020 Fungal Resistancy Test
Observed Fungal Growth after 14 Fungus Fungus
Sample Days incubation at 28 C Non-
Resistant Resistant
1 2 3
Control Diluent DMSO Growth Growth Growth x
Metasol-TK 100 200ppm No Growth No Growth No Growth x
Metasol-TK 100 400ppm No Growth No Growth No Growth x
Metasol-TK 100 600ppm No Growth No Growth No Growth x
Tox-Guard*Dry 200ppm Growth Growth Growth x
Tox-Guard*Dry 400ppm Growth Growth Growth x
Tox-Guard*Dry 600ppm Growth Growth Growth x
Santoquin 200ppm Growth Growth Growth x
Santoquin 400ppm No Growth No Growth No Growth x
Santoquin 600ppm No Growth No Growth No Growth X
BIOX-AUSD 200ppm Growth Growth Growth x
BIOX-AUSD 400ppm Growth Growth Growth x
BIOX-AUSD 600ppm Growth Growth Growth X
Mintrex Cu 200ppm Growth Growth Growth x
Mintrex Cu 400ppm Growth Growth Growth x
Mintrex Cu 600ppm Growth Growth Growth X

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Table 2. Santoquin Performance in ASTM D 2020 Fungal Resistancy Test
Observed Fungal Growth after 14 Fungus Fungus
Sample Days incubation at 28 C Non- Resistant
Resistant
Santoquin 0.1 %-1 No growth x
Santoquin 0.1%-2 No growth x
Santoquin 0.1 %-3 No growth x
Santoquin 1.0%-1 No growth x
Santoquin 1.0%-2 No growth x
Santoquin 1.0%-3 No growth x
Kathon 893 0.1 %-1 Growth x
Kathon 893 0.1 %-2 Growth x
Kathon 893 0.1%-3 Growth x
Kathon 893 1.0%-1 Growth x
Kathon 893 1.0%-2 Growth x
Kathon 893 1.0%-3 Growth x
DMSO-1 Growth X
DMSO-2 Growth x
DMSO-3 Growth x
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Table 3. Anti-Fungal Activity of Test Agents
Test Agent Minimum Total Inhibitory
Concentration %
Cinnamaldehyde <0.005
Dehydroacetic Acid 0.01
Propyl Paraben 0.015
EDTA 0.02
BHA (Butylated H drox Anisole 0.025
Copper Sulfate 0.05
Eugenol 0.05
Alpha Lipoic Acid 0.1
Benzoic Acid 0.1
Beta-Propiolactone 0.1
Carvone 0.1
Citral 0.1
Diacetyl 0.1
H drogen Peroxide 0.1
Piperonal 0.1
Sodium Metabisulfite 0.1
Sulfuric Acid 0.1
TBHQ Tert-But IH droQuinone 0.1
Valeric Acid 0.1
Vanillin 0.1
Acetic Acid 0.2
Activate DA 0.2
Alimet HMTBA /Pro ionic Acid (1:3) 0.2
Butyric Acid 0.2
Hexadec I ridinium Cl 0.2
Proprionic Acid 0.2
Sodium Bisulfite 0.2
Xtract 0.2
65%Pro /20%L s/15%NH4OH 0.5
65%Pro /35%NH4OH 0.5
Benzaldehyde 0.5
Boric Acid 0.5
Copper Mintrex Cu HMTBA 2 0.5
EQ Ethox uin Emulsion 0.5
HCI 0.5
Maleic Acid 0.5
Methyl Paraben 0.5
Phosphoric Acid 0.5
Sodium Diacetate 0.5
Acetaldehyde >0.2
Culbac Liquid >0.2
3-H drox -2-Butanone >0.5
3-H drox ro ionic Acid >0.5
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Adipic Acid >0.5
Alpha Tocopherol >0.5
Alpha Toco herol Acetate >0.5
Ascorbic Acid >0.5
Ascorbyl Palmitate >0.5
BHT (Butylated H drox Toluene >0.5
Calcium Acetate >0.5
Calcium Pro ionate >0.5
Citric Acid >0.5
Cysteine >0.5
Decanal >0.5
Delta Tocopherol >0.5
Dilauryl Thiodi ro ionate >0.5
Dodecyl Gallate >0.5
Ethanol >0.5
Ethoxyguin >0.5
Fumaric Acid >0.5
Gallic Acid >0.5
Gluconic Acid >0.5
Glycine >0.5
Glycolic Acid >0.5
HMTBA (2-Hydroxy- >0.5
4 NMeth IThio Butanoic Acid)
Lactic Acid >0.5
Lecithin >0.5
Limonene >0.5
Lysine >0.5
Malonic Acid >0.5
Methionine >0.5
MHA (Methionine Hydroxy Analog) >0.5
Octyl Gallate >0.5
Potassium Acetate >0.5
Potassium Benzoate >0.5
Potassium Sorbate >0.5
Propyl Gallate >0.5
Sodium Acetate >0.5
Sodium Benzoate >0.5
Sodium bi-Phosphate >0.5
Sodium Citrate >0.5
Sodium Gluconate >0.5
Sodium Hexametap hosp hate >0.5
Sodium Lactate >0.5
Sodium Proprionate >0.5
Sodium P ro hos hate >0.5
Sodium Sulfite >0.5
Sodium Thiosulfate >0.5
Stearyl Citrate >0.5
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Tartaric Acid >0.5
ToxGuard Liquid (New sam le >0.5
Tr to han >0.5
DMSO >1
ToxGuard Liquid (Old sam le >2
ToxGuard Dry (Old sample >3
ToxGuard Dry (New sam le >5
24