Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
-
This invention relates to an improved antimicrobial agent
that is effPctive against broad groups of microorganisms, and more
particularly relates in a preferred embodiment to an improved anti-
microbial agent that has low toxicity for animal and plant life.
The inventhon essentially is directed to the ~ormulation of
a disubstituted aryl compound in which the first substituent is an
oleophilic group adapted to penetrate the lipoid layers of microcells
and the second substituent is a hydrophilic group to which an anti-
microbial agent is coordinated. By coordinating the antimicrobial
agent with the disubstituted aryl compound, a synergistic effect is
observed in which there is a marked increase in the mocrobicidal
activity of the antimicrobial agent, which activity is far greater
than can be accounted for by the contribution of any antimicrobial
properties of the disubstituted aryl compound. Since the anti-
microbial agent is coordinated with the hydrophilic constituent,
the antimicrobial agent is solubilized on a molecular basis. By
coordinating the antimicrobial agent with the aryl compound, the ~;
antimicrobial agent can be carried along~with the compound and so
be poised to enter a cell when its protective membrane is breached
by the combined attack of hydrophilic and oleophilic substituents `
of the aryl compound.
The coordinate bond between the disubstituted aryl compound
and the microbicidal agent may be broken by conventional means such
as formation of an insol!uble or nonionizable compound from either
,
of the two components of the coordinate bond. It is desirable at
times to guard against such bond-breaking by means such as pH
adjustment or chelation of undesirable ions.
For the protection of certain substrates, it actually may be
desirable, however, to allow the coordinate bond to break during
or after treatment of the substrate. This happens in the treatment
of wood, for example, so that once deposited in the wood, the anti-
microbial agent changes from a water-soluble to a water-insoluble
:
form, thereby retaining high residual activity. In this case, the
initial coordinate bond has served a very useful purpose in
allowing the antimicrobial agent to be deposited within and on the
wood on a molecular basis.
SUMMARY STATEMENT OF T~E INVENTION
According to the invention, there is provided an improved
antimicrobial composition constituted as a substituted aryl
compound including an oleophilic substituent, a hydrophilic substit-
uent, and an antimicrobial agent coordinated with the hydrophilic
substituent.
In one aspect the invention may be understood to provide
an alkyl group compatible with the semipermeable membrane of the
microbe to be controlled, as the oleophilic substituent.
From a further aspect the invention provides that such alkyl
group is substantially straight-chained and contains about six to
about twenty-four carbon atoms.
From yet another aspect the invention contemplates that the
alkyl group has six or less carbon atoms and includes a chlorine
substituent.
It is a further provision of the invention that the anti-
microbial composition may have a water-soluble hydrophilic substit-
uent, in the ionizable sense; and that such hydrophilic substituent
is a sulfo or hydroxyl group. -
The invention also contemplates the provision of a p~henyl
or naphthyl as the substituted aryl.
In a specific form the invention may utilize as antimicrobial
agent a metal chelate of oxine.
In another specific form the invention may utilize as anti-
microbial agent a metal chelate of oxine, where the metal is mercury,
copper, cadmium, nickel, tin, aluminum, or zinc.
The antimicrobial composition according to the invention
may also comprise alkyl (C6 to C18) benzene sulfonic acid coordin-
~ - 2 -
: ';
- .. . . ~... . : .
:
ated with a metal chelate of oxine; or it may comprise an alkyl (C6 to C18)
substituted phenol coordinated through the hydraxyl group.
The invention further provides that there may be utilized as
active antimicrobial agent, an imidazole, a benzimidazole, or a thiazole,
and that such active antimicrobial agent ma~ be: 2-~4-thiazolyl) benzimidazole
diiodomethyl-para-tolyl sulfone; para-chloro-phenol diiodomethylsulfone;
2-n-octyl-4-isothiazolin-3-one; 2-benziisothiazolin-3-one; or 8-h-ydroxy
quinoline.
Accordingly, the present invention relates to a composition
comprising an insecticidal agent or an antimicrobial agent selected from the
group consisting of metal chelates or oxine, imidazoles, benzimidazoles,
thiazoles, diiodomethyl-para-tolyl sulfone, para-chlorphenol diiodomethyl
sulfone, 2-n-octyl-4-isothiazolin-3-one, 2-benzisothiazolin-3-one, 8~hydroxy-
qulnoline and cis-N-(trichlorcmethyl)thio-4-cyclohexane-1,2-dicar~oximide in
combination with an aryl co~pound having one hydrophilic and one oleophilic
substituent, said aryl compound being present in an am~unt sufficient to
solubilize the insecticidal or antimicrobial agent.
The inventicn contemplates as practical compositions, a mixture of~
1-10 parts by ~eight of an antimicrobial or insecticidal agent; 5 - 83 parts
by weight of a disubstituted aryl compoundi and 1 - 50 parts by weight of
a polar diluent; further providing that the disubstituted aryl ccmpound
includes an oleophilic substituent, a hydrophilic substituent, c~nd that the
active antimicrobial or insecticidal agent is coordinated with the hydrophilic
substituent.
As an extension of the aspect recited immediately hereinabove the
polar diluent may be selected fro~ methc~nol, ethanol, isopropanol, n-butanol,
dimethylformamide, N-methyl-pyrrolidone, ethylene glycol, propylene glycol
or water.
~ 'rom yet another aspect the invention may be understood to provide
a method of preparing a novel antimicrobial c~mpositian, wl~ch comprises add
ing 1 to 10 parts by weight of c~n antimicrobial agent to 5 to 83 p~arts by
weight of an aryl compound disubstituted with an oleophilic alkyl group
- 3 -
',
. ~
.~ , .. . . . . ......... . .
:.: . .. . - ... : , . . . .
coNtaining 6 to 24 car~on atoms and a hydrophilic hydroxyl or sul~o group
and 1 to 50 pa~ts by weight o~ a water-soluble polar organic solvent to
co~rdinate the antimicrobial agent with the hydrophilic group and effect
solubilization of the antimicrobial agent.
In the method recited hereinabove the imlention may further
provide as antimicrobial agent the reaction product of a metal salt~ oxide
or hydroxide with 8-hydr~xyqulnoline; and such reaction may be arranged to
proceed in situ in the antimicrobial composition.
'
- 3a -
..
THE OLEOPHILIC SUBSTITUENT
The oleophilic substituent of the compos;tion of this
invention should have a degree of stereochemical compatibility
with the structure of the semipermeable membrane of the cell. A
common structure meeting this criterion is an essentially unsubst-
ituted straight-chained hydrocarbon having a length that is
significant with respect to the thickness of the cell wall. This
generally requires, as a minimum9 an alkyl chain with about six car-
; bon atoms in it. On the other hand, the alkyl chain should not
be too long; since the freedom of mobility of an alkyl chain
increases with ;ncreasing chain length, alkyl chains begin to coil
if a certain length is exceeded. When the coiling is significant,
it can cause steric hindrance and make permeation of the cell
wall difficult. While the maximum length of the alkyl chain can
only be determined with respect to a given environment and a
specific cell structure, it is believed to be a fair generalization
to suggest that an alkyl chain much longer than 1~ carbon atoms, -
and, more especially, one longer than 24 carbon atoms, will lose
its effectiveness in penetrating the cell wall.
The preferred alkyl groups of this invention are not
excessively branched or substituted to the extent that they lead
to steric hindrance. Nonetheless, some substitutes along the
hydrocarbon chain, such as chlorine, may improve the oleophilic ~ -
properties of the "shaped charge" and may be used to advantage. It
has also been observed that chlorine substitution may permit the
use of shorter alkyl chains.
It can be understood that no rigid definition can be given
as to the length, composition and configuration of the oleophilic
group as these parameters necessarily must be adjusted for the
microbial species of the bacteria and fungi that are to be attacked.
- 4 -
T~E HYDROPHILIC SUBSTITUENT
The hydrophilic substituent of the aryl campound must be
capable of forming a strong coordinate bond with the microbicidal
agent. There are not many hydrophilic substituents to choose from
that will coordinate well with a compound having microbicidal
properties, and two of the most effective and chemically accessible
are the~ulfo and the hydroxyl radicals.
THE ARYL COMPOUND
A preferred aryl compound is benzene which is believed
to be most effective and, perhaps to a lesser extent, naphthalene.
Aryl compounds comprised of more than two ring structures may -
lose their effectiveness for several reasons, among them being the
fact that their size becomes large as compared with the oleophilic
substituent and will tend to cause steric hindrance to the oleo-
philic substituent in penetrating the wall of the microorganism.
While not essential in the practice of this invention, secondary
substituents of the aryl group may sometimes prove desirable,
particularly if they are capable of withdrawing electrons to
increase the strength of the coordination bond between the hydro-
philic substituent and the microbicidal agent. Substituents which
function in this manner are, for example, -N02, -CN and -CHO.
Electron-withdraw;ng substituents should be used sparingly and
with discretion if overloading of the ring structure of the aryl
compound is to be avoided. ;
THE ANTIMICROBIAL AGENT
As set forth above, the antimicrobial agent must coordin
ate with the hydrophilic substituent to form a reasonably stable
bond if it is to be solubilized and be effective in the practice
of this invention.
One particular advantage of this invention lies in the fact
; that antimicrobial agents that have known low toxicity toward
plant and animal life may be made more effective by formulating
- 5 -
~ '.
.. . . ..
,r~
them in accordance with this invention, thus greatly increasing
their utility. Of these, for example, the metal chelates of
8-hydroxy-quinolinol (oxine) are quite prominent, particularly
copper-8-quinolinolate (hereinafter called "Cu-8-Q"). The follow-
ing is a listing taken from literature references of the relative
effectiveness of several metal quinolinolates in descending order
of activity:
mercury
copper
cadmium
nickel
lead
cobalt
zinc
iron
calcium. ~
Aluminum and tin have also proved useful. ;
Other groups of compounds which have been found effective as
ant;microbial agents when coordinated with substituted aryl compos-
itions of this invention include the imidazoles and the thiazoles.One of particularly good microb;cidal activity is a benzim;dazole
marketed by Riedel-de-Haen AG of Seelze/Hanover, West GErmany, ~ ;
under its product designation "Mergal BCM", which is believed to
be 2-(methoxy-carbamoyl)-benzimidazol. ~ i
The follow;ng Examples are given to show the effect;veness
of one of the preferred microbicidal compositions of this invention
in which dodecylbenzene sulfonic acid (DDBSA) is selected as the
disubstituted aryl compound and ~u-8-Q is selected as the microbicide.
The oleophilic substituent of the benzene ring of DDBSA is the 12-
carbon-membered (approximately) alkyl chain and the hydroph;lic
substituent is the fulfo group. The oleophilic hydrocarbon chain
on the DDBSA is essentially a tetramer of propylene and usually
will vary, as commercially available, from between 11 and 13 carbon
atoms. Most DDBSA commonly available is straight-chained, but
-- 6
some is branched (the so-called "soft" and "hard" DDBSA's), and
both have proven effective in the practice of this invention.
The Cu~-Q used in the Examples is prepared by the reaction
of 8-hydroxy quinolinol with a copper compound such as copper
hydrate (cupric hydroxide). -
A diluent is used with the mixture of DDBSA and cu-8-n
which not only serves as a viscosity-reducing agent, but also, it
is believed, permits ionization of the alkyl benzene sulfonic acid
to achieve complete solubility of the compound. It has been found
that complete solubilization is effected most easily through the
use of a highly polar organic solvent which is water miscible; a
partial list of suitable diluents for use in the present invention
is given immediately below:
Methanol
Ethanol
Isopropanol
n-Butanol -
Dimethylformamide
N-methyl-2-pyrrolidone
Ethylene glycol
Water
Propylene glycol
Stoddard solvent
Toluene
Broadly speaking, for every part by weight of the metal-8-
quinolinate, it is preferred to include from 5 to 50 parts by
weight DDBSA and I to 50 parts by weight of the polar diluent. The
most preferred composition according to the present invention
contains from 2 to 10 parts by weight of Cu-8-Q, 25 to 83 parts by
weight of the alkyl benzene sulfonic acid, and 15 to 35 parts by
weight of the diluent per 100 parts by weight of the concentrate.
One specific composition produced according to the present invention
contains about 5 parts by weight of Cu-8-Q, about 64 parts by weight
of DDBSA, and about 31 parts by weight of methanol. Additionally,
it has been found useful to add minor amounts, e.g., 5% by weight,
of ethylene glycol, to improve shelf life.
. - . . .
One method of producing the compositions of the present
invention is to mix the diluent with the DDBSA and stir in the
- 7 -
quinolinate. The mixing may be accompanied by liberation of
exothermic heat of reaction which speeds up the solution of all
components.
Another suitable process ~or preparing the concentrate
consists in first reacting copper hydroxide with a mixture of
methanol and DDBSA to form a metal salt. Then 8-hydroxy quinoline
is stirred in to form the metal chelate.
The concentrates prepared as above are diluted, preferably
with water, prior to use and essentially may be diluted to any
degree. Other diluents may be used, including xylene, -isopropanol,
ethylene glycol, and napththa. The diluted solutions can be
applied by a known technique, such as brushing, spraying, dipping
or wiping.
In the Examples that Follow, the efFectiveness of the
various formulations was determined by treating freshly cut pine
boards by dip immersion for 10 seconds in the formulation to be
tested. The boards, along with an untreated control board, were
placed in a chamber for a period of time indicated and mainta;ned
at a temperature of about 80F and a humidity of about 70%.
When the boards were removed from the chamber, they were
visually compared with the control. The results of the effective-
ness of the fungicide are expressed as the percentage of the total
surface area of the board covered by stain and mold. Thus, the
lower the percentage, the better the activity as a fungicide.
All parts given in the Examples are parts by weight.
E X A M P E E S
~ .
Examples I to I I I .
To establish the inherent fungicidal properties of
Cu-8-Q, it was dissolved in a strong mineral acid and in maleic
acid and the results compared with a solution of similar Cu-8-Q
concentration made in accordance with this invention. Each Example
was diluted 1:400 with water for use.
Cu-8-Q Solubilizing Agent Diluent and %Stain
Example Amount and Amount Amount 42 Days
- :
~ - 8 -
I 10 DDBSA/50 Methanol/40 29
II 10 98% H2S04/20 Water/70 53
III 10 Maleic acid/50 Water/40 58
As can be seen, dissolving Cu-~-Q in sulfuric acid and in
Maleic acid is not nearly as effective as solubilizing it with a
disubstituted aryl compound of the instant invention.
EXAMPLES IV to VIII :~
In these Examples, Cu-8-0 was dissolved in compounds
closely related to DDBSA save for the fact that they did not
have the oleophilic substituent or "shaped charge" as described
in this specification.
In the Examples IV to VIII that follow, the data given in
the table is for the concentrate. In all cases, th;s concentrate
was diluted by 400 parts water to 1 part concentrate prior to
treating the test specimen.
Example Cu-8-Q Solubilizing agent Diluent and % Stain
_No. Amount and Amount Amount ~ s
IV 5 DDBSAj64 Methanol/31 17 ;~
V 5 ~p-toluene sulfonic Methanol/31 52
acid/64
VI 5 1-napthalene sul- Methanol/31 74
fonic acid/64
VII 5 Benzene sulfonic Methanol/31 92 -
acid/64
VIII 5 Methane sulfonic Methanol/31 62
From the foregoing, it can be seen that compounds formed -
~by the substitution of a sulfonic group on an otherwise unsubstit-
uted aryl compound are quite effective as fungicides. Some improve- ~
ment is noted by additionally substituting a methyl group, but a ~;
most dramatic improvement is noted if the second substituent is a ~ ~
12-carbon alkyl group that is an oleophilic shaped charge within ~ -
the scope of this 1nvention. Tridecylbenzene sulfonic acid proved
very efFective, too. However, 4-dodecylated oxydibenzene sulfonic
acid proved less effective although it is considered useful in
g
certain instances and within the scope of this invention.
EXAMPLES IX to XI
In order to prove the effectiveness of a fungicide
made in accordance with this invention, the composition of Example IV
was diluted 1:200 wi~h water and treated boards compared with
those treated with three of the standard fungicidal compositions
now in common use.
% Stain and Mold, 28 d.
EXAMPLE Test 1 Test 2
No. Sodium tetrachlorophenate 16.40% 20 7
Other sodium chlorophenates 4.43%
IX Phenyl mercuric lactate 0.40%
Inerts 65.11%
Methanol 13.~6%
Dilution: 1:100 in water.
DDBSA/50% 2 l2
X Tetrachlorophenol 34.23%
2,4,5 trichlorophenol 1.90%
other chlorinated phenols 9.25%
Inerts 4.62%
Dilution: 1:250 in water
XI Borax 57.0%
Sodium pentachlorophenate 31.6% 2
Other sodium chlorophenates 4,4%
Inerts 7.0%
Dilution: 10 lbs./800 lbs. water.
In contrast to the foregoing, the control treated with the
composition of Example IV eviced 17% stain and mold in Test 1, and
0% in Test 2.
EXAMPLE XI I
The followin0 composition was prepared in accordance
with previously stated techniques:
copper hydrate: 1.70 -~
8-hydroxy quinoline 4.44
DDBSA 6`4.81
Methanol 15.05
Isopropanol 14.00
This composition was diluted with water and tested, in
compàrison with a sodium tetrachlorophenate (23%) liquid concentrate
also diluted in water, against organisms on three species of green
;~ 40 lumber: Douglas Fir, Amabilis Fir, and Ponderosa Pine. The
organisms were:
' - 1 0 - , "
, '
~,
~$~i;A~
, . .
Cephaloascus fragrans - a brown mold that ;nfests
certain wood species.
Trichoderma virgatum a common mold
Mixed spores a combination of two molds:
(Penicillium sp. and Aspergillis
niger) ancl a fungus (Ceratocystis
pilifera) that causes blue stain
in wood.
The freshly cut wood samples were dip treated (15-second
immersion) with the test fungicides and then inoculated with spore
suspensions oF the above described fungi. The test boards, together
with untreated control boards, were then placed in a warm, humid
chamber for four weeks. The results are set forth in the table
below in which:
A = Douglas Fir 0 = no growth
B = Amabilis Fir 1 = no growth in 2 weeks
C = Ponderosa Pine 2 = medium ~rowth
X = C. fragrans
3 = heavy growth, 4 weeks
Y = T. virgatum
4 = heavy yrowth, 2 weeks
Z = Mixed Spores
XA XB XC YA YB YC ~A ZB ZC
Tetrachlorophenol composition 1:100 4 4 4 0 0 3 3 4 4
Example XII composition 1:240 2 0 1 3 0 4 4 3 4
Tetrachlorophenol composition 1:50 2 0 4 0 0 1 3 2 4 -~
Example XII composition 1:250 0 0 1 3 0 1 2 2 2
Tetrachlorophenol composition 1:25 2 2 3 0 0 1 0 0 3
Example XII composition 1:60 0 0 0 1 0 0 0 0 0
Tetrachlorophenol composition 1:12/5 0 1 0 0 0 0 0 0 2
Exampl~ XII composition 1:30 0 0 0 0 0 0 0 0 0
Controls (no treatment) 4 4 4 3 4 4 4 4 4
; 30 The chlorophenol composition above is typical of the type
employed to control sap stain and mold in green lumber. In the
case of the tested wood species, the chlorophenol types are noted,
:.. ~
however, for poor control of C. fragrams, the result of which is
common use of mercury-based fyb~icides (such as phenyl mecuric
acetate) in combination with the chlorophenol to achieve needed
control. The composition of Example XII, however, does exhibit
- 1 1 - ,
' ,
.. . . . . - . . . . .. . . ~ .
superior control of C. fragrans. .
~XAMPLES XIII to XVII
To demonstrate the fungicidal properties of various
metal-8-quinolinolates, solutions were prepared using 5 parts of
the indicated metal-8-~uinolinolate, 64 parts DDBSA and 31 parts
methanol.
Metal Ouino- % Stain
Example linolate 28 Days
XIII Copper 17
XIV Tin 20
XV Aluminum 28
XVI Nickel 39
XVII Zinc 46
The foregoing metal-8-quinolinolates also may be prepared by
in-situ reactin~ oxine with an appropriate metal in the DDBSA/
Methanol reaction medium.
Example XV I I I
~; A Cu-8-Q fungicidal formulation was prepared utilizing - ~.
substituted aryl compounds of the alkyl phenol type to demonstrate
the e~fectiveness of a hydroxyl ~roup replacement for the sulfo
group as the hydrophilic substituent in the practice of this invention
Copper hydrate 1.
8-hydroxy quinoline 4.1
Nonyl phenol 74.5
Heavy armoatic naphtha 20.0 ::
The above mixture of ingredients was heated at 180F
until solution of the Cu-8-Q, formed in situ, was complete. This .
composition then was reduced from 5% Cu-8-Q content to 0.25% by
dilution with mineral spirits.
; Cotton duck cloth (10 oz.) was treated to refusal by dip :
immersion in the test solution, dried and buried in sheep manure ~
saturated with water. At the same time, control cloth was buried .. .
to~ether with the cloth treated as stated, and together with cloth
treated with a commercial Cu-8-Q composition (Cunilate 217~)
solubi~ized in nickel acetate and 2-ethyl hexoic acid containing
- - 12 -
0.25% Cu-8-Q in a mineral spirits carrier. At the end of 28 days
at 75F, the cloths were removed from the sheep manure, washed
and checked for loss in strength, with these results:
Untreated cotton duck - Very high strength loss
Example XVII~ composition - zero to very low loss
Cunilate 2174 treated - moderate strength loss
Example XIX
Another test evaluation illustrates the considerable
effectiveness of the composition of Example XVIII against Lenzites
trabea , a widespread fungus causing destructive wood decay,
especially in above-ground locations where very few types of decay
fungi can withstand the elevated temperatures encountered. The
test method employed is an industry standard -- the National
Woodwork Manufacturers' Association M-1-70 Soil Block Test. It
consists of treating, by impregnation to saturation, of Ponderosa
Pine blocks with the test fungicide solution in a toluene carrier.
After drying, the blocks are subjected to a severe water leaching ; ;
procedure, after which the blocks are redried and inoculated with
a Lenzites trabea fungus culture. At the end of the test period,
the blocks are measured for weight loss which indicates the
degree of wood decay.
Example XVI I I 0 . 028~ Cu-8-Q - 15 . 0% Weight loss
Example XVIII ~.065% Gu-8-Q 5.6%
Cunilate 2174 0.093% Cu-8-Q 21.9%
It is plainly evident that the composition of this invention
used in the foregoing test provides superior protection to the wood.
Xylene, benzene, toluene, Stoddard solvent, heavy petroleum
oils and naphthas are suitable for diluting this class of compos-
itions of this invention. Generally, solvents with higher aromatic-
ity provide longer solution stability -- i.e. no precipitation of
Cu-8-Q. Greater solution stability is achieved by increasing the
ratio of alkyl phenyl to Cu-8-Q and/or by increasing the ratio of -
- 13 -
:.
, : . - . : .
alkyl phenol to Cu-8-Q and/or by increasing the ratio of alkyl
phenol/Cu-8-Q composition to petroleum solvent and/or diluent.
Generally preferred are the alkyl phenols which are
liquid at room temperature, particularly nonyl and dodecylphenol
because of low cost and commercial availability.
To impart additional water repellency to this class of
compositions, waxes and certain resins, including certain silicone
and resin ester resins,may be incorporated, as may other means
well known in the art.
Examples XX to XXII
To demonstrate the very real synergistic effect
achieved in the practice of this invention, Cu-8-Q and DDBSA were
tested alone and combined to determine their effectiveness in
controllin~ mold and sap stain on freshly cut lumber.
ExampleFormwlation % Mold at 28 Days ~ -
XXX'~^'0.025% Cu-&-Q aqueous 89
dispersion
XXI0.035% DDBSA aqueous
solution
XXII*Mixture of the solutions
of Examples XX and XXI 6
(*agitated for 30-60 minutes before use to allow formation
of coordinate bond between Cu-8-Q and DDBSA)
Examples XXIII to XXIX
As further evidence of the effectiveness of micro-
bicides prepared in accordance with this invention, a number of
tests were conducted utilizing DDBSA as the substituted aryl
compound of this invention coordinated with the below-listed
microbicidal agents. A 1:200 use dilution in water was prepared
from concentrates containing 65 parts DDBSA, 30 parts Methanol,
and 5 parts of the microbicidal agent. Fresh-cut green pine test
boards were dip-treated and evaluated for stain and mold after 30
days in the aforementioned constant atmosphere chamber:
14
2~
Example Microbicidal Agent % Mold & Stain
.
XXIII Cu-8-Q 3
XXIV 2-(4-thiazolyl) benzimida~ole 14
XXV cis-N-(trichloromethyl) thio 23
~-cyclohexane-1,2-dicarboximide
XXVI diiodomethyl-para-tolyl sulfone 8
XXVII para-chlorophenol diiodomethyl 6
sulfone
XXVIII 2-n-octyl-4-isothiazolin-3-one 10
XXIX 2-benzisothiazolin-3-one 14
XXX 2-(methoxy-carbamoyl)-benzimidazol 2
XXXI 8-hydroxy quinoline 10
In some instances, it may prove advantageous to include
-~ other microbicides in a given formulation to increase the over-all
spectrum of antimicrobial activity. Such additional microbicides
need not necessarily be o~ the type thus far described in this ~
; specification. For example, when treating ~reen lumber to inhibit
sap stain or mold, it is somet;mes desirable, to get broader
protection, to include a chlorophenol such as pentachlorophenol, : .
tetrachlorophenol, or 2,4,5-trichlorophenol, in the composition of .
this invention. It is also within the scope oF this invention to .~
include insecticides. Surprisingly, it has been found that when .~
a number of well-known insecticides are added to water-soluble :
..
compos;tions of this invention, the insecticide is solubilized and ~ ;
remains so when diluted with water for use. Insecticides exhibit-
ing such unusual behaviour include:
0,0-dimethyl-S-(1,2-dicarbethoxyethyl)phosphorodithionat;
.l 1,2,4~5,6,7,8,8-octochloro-2,3,3a,4,7,7a-hexahydro-4,7- ~ ..
; methanoiodane;
. 1,1,1-trichloro-2,2-bis(p-methoxyphenyl)ethanol; and .. ;
1-naphthyl N-methylcarbamate.
These widely used insecticides have heretofore been available only
in non-water=soluble ~orms such as dusts, wettable powders and
emulsifiable concentrates. Availability as true water solutions
oFFers considerable advantage in handling, mixing, stability and
application uniFormity.
- 15 -
i2~i
Example XXXII
Some of the compositions of this invention exhibit unexp-
ected insecticidal activity when compared to the conventional
solubilized Cu-8-Q compositions and when compared to a known
insecticide (pentachlorophenol). Against termites in a soil burial
test in Memphis, Tennessee, the following compositions were
evaluated: .
(a) Example XII, diluted with water to a 0.25% Cu-8-Q
content;
(b) Example XVIII, diluted with mineral spirits to a
0.25% Cu-8-Q content;
(c) Cunilate 2174, diluted with mineral spirits to a
0.25% Cu-8-Q content, and
(d) A 5.0% pentachlorophenol solution in mineral spirits
containing 4% propylene glycol ether to provide
sufficient pentachlorophenol solubility and to
prevent sublimation from the wood. ~ :
Dry southern yellow pine stakes, 3/4" square x 24" long,
were dip-impregnated with the test solutions, allowed to dry for
20 one week, and then buried to a depth of 12" in the ground for 15
months, at which time these results were observed:
Solution ~ickup Termite
Treatment (lbs/ft ) Rating* _
None (control stakes) -- 36
Example XII 1.79 83
Example XVIII 1.13 80
5% pentachlorophenol 1.28 84
solution
Cunilate 2174 1.26 56 ~ . -
(*Termite Rating:
0 = stakes totally destroyed;
100 = stakes unattacked.
Both compositions of this invention exhibited termite
control essentially equal to that of pentachlorophenol solution
and definitely superior to both the untreated control stakes and
those treated with Cunilate 2174.
.
- 16 -
:
$ ~
Example XXXIII
The composition set forth below was prepared by
previously described procedures:
copper hydrate 0.70
8-hydroxy quinoline 2.08
Isopropanol 32.00
DDBSA 40-00
Water, demineralized 25.22
When evaluated as a germicide by the A.O.A.C. Use Dilution i-
Method (12th Edition, 1975), use dilution in distilled water, 10
ring carriers per organism (incubated at 27C For 48 hours), the
results set forth in the table below were obtained after 10 -
minutes contact time at 20C. In the table, A = subculture and
B = resubculture
NegatlvePos~tlve
Use Dilution A B A B
Staphylococcus aureous 1:500 10 10 0 0
Salmonella cholerasuis 1:500 10 10 0 0
Pseudomonas aeruginosa 1:400 10 10 0 0
Aerobacter aerogenes 1:500 10 10 0 0
(The calculated acute LD of the foregoing
formulation prior to diq~tion with water for
use is 4160 mg. per kilogram of body weight,
(rat, oral administration) ).
A 10-minute kill is required by the Environmental Protec-
tion Agency - an agency of the United States government - against
the first three pathogens to permit a germicide to be offered ~or
sale as a hospital germicide. The fourth organism is a major cause
of slime in recirculated cooling water systems and pulp and paper
mills, thereby indicating the usefulness of the composition as a
; 30 slimicide.
Example XXXIV
Using approved A.O.A.C. methods for fungal evaluation,
the composition of Example XXXIII was evaluated as a fungicide
against Aspergillis niger ~a widespread black mold) and Trichophyton
mentagro~tes (known as the cause of 'athlete's foot'):
:'..-''.
~ : '
,
. . .
r$~ J ~
Aspergillis niger - 1:200 use dilution in distilled
water - no growth after 10 minute
exposure;
Trichophyton mentagrophytes - 1:750 use dilution in
distilled water - no ~rowth a~ter
10 minutes exposure.
Similar results were obtained by substituting zinc-8-
quinolinolate or aluminum-8-quinolinolate in the composition of
this Example; sinc oxide and aluminum hydroxide are reacted
respectively with 8-hydroxy quinoline instead of copper hydrate.
Example XXXV
' .'
Copper hydrate 0.70
8-hydroxy quinoline 2.08
Nonyl phenol-E0
surfactant* 20.00
DDBSA 45.00
Isopropanol 15.00
Water, distilled 17.22
~ (* 1 mol nonyl phenol to 6 mols ethylene oxide).
; 20 The composition was prepared by the procedure already
described and evaluated for efficacy against ciliated protozoan
and two types of viruses with these results:
Hemaglutination Assays
**
HA Titre
Untreated Treated (1:50)* Treated
Virus (1:200*)
.
Adenovirus 128 0 0
Newcastle Disease
virus 512 0 0
(*1:50 and 1:200 use dilutions of compositions in
water in contact with virus suspension for 15 minutes)
(** HA Titre is a measure of the number of infectious
virus particles present in the test suspension).
Pla~e Assays
Via the same procedure as above, the untreated virus susp- -
ensions contained ~ ~ x 104 pfu/ml of Adenovirus particles and
21 x 105 pfu/ml Newcastle Disease virus particles, respectively.
After treatment with the 1:50 and 1:200 use dilutions, readings of
.'
- 18 -
'.
0 pfu/ml were obtained. i~ch pfu unit represents one infectious
virus particle. A reading of zero pfu represents total inactiv-
ation of the infectious virus.
Protozoan Inhibition
.
Inhibition o-f growth of ciliated protozoan (Tetrahymena)
in pond water was obtained at a 6 ppm concentration of test compos-
ition after 6 hour and 72 hour contact times. l~e 6 ppm reading
represents the MIC (Minimum Inhibitory Concentration~. ;
T~e following data illustrates the high efficacy of the
composition against the microorganisms tested:
Example XXXVI
The compositions of this invention exhibit control of
a number of plant and crop diseases, as illustrated by using the
followiny composition:
Copper hydrate 1.70
8-hydroxy quinoline 4.4~
Isopropanol 35.00
DDBSA 58.86
~ Valencia oranges
; 20 The composition was tested on harvested fruit against
Phompsis stem-end rot and Diplodis rot, at a 1:100 use dilution
in water, 2-minute dip application. After 3 weeks at 70F, the
followin~ percentages of decay were noted:
Control (untreated) oranges - 9.5% rot.
Treated oranges - 5.3% rot.
B. Sugar Cane
An agar seeding test against Ceratocystis paradoxa
(which causes rotting at the seed pieces) at a 1:10,000 (100 ppm)
use dilution ;n water exhibited a 3.0 mm inhibition zone. :
C. Peach trees -
T~e composition was tested against Taphrina deformans
(which causes leaf curl disease), by spraying four trees twice with
an interval of two weeks, with a 1:400 use dilution in water. Three
- 19 - :
.. . .
:
, . . . .. ... . . . . . .
2 ~ ~ :
months later, 100 leaves on each test tree were rated for leaf
curl:
Treated leaves - 13.5% leaf curl
Control (untreatecl) 100 % leaf curl.
D. Cotton
Effectiveness against six fungi and one bacterium
~Xanthomonas malvecearum) that are associated with disease of
cottonseed or seedlings and other plants was evaluated in vitro,
using the ~ollowing compositions, respectively numbered #1 and #2:
Composition #1 Copper hydrate1.70
8-hydroxy quinoline 4.44
Methanol 4.00
Isopropanol 30.86
DDBSA 59.00
Composition #2 Copper hydrate2.80
8-hydroxy quinoline 8.20
Methanol 4.00
Isopropanol 26.00
DDBSA 59.00
Both compositions were prepared in accordance with
procedures described in previous Examples.
The following results were obtained5 expressed in terms
of parts per million (ppm) of test composition in water and the
relative growth inhibition provided at each test strength on the
respective organisms. In the table below:
O designates no apparent inhibition;
1 indicates some inhibition
2 indicates considerable inhibition, i.e.
little growthi
3 indicates total inhibition - no ~rowth.
,, .
Composition #1 Tests 01 5 25 100 500 1000
Test Organisms Concentrations, parts per million (ppm)
.
Pythium ultimum (41B) O O 0 1 2 3 3
Rhizoctonia solani (lD) 9 0 9 1 ~ 3 3
Fusarium (4A) O 3 3 3 3
Fusarium (4D) O 1 1 2 2 2 3
Fusarium roseum (4C) O O 0 1 2 2 3
Colletotrichum gossypii (35A) O O 0 1 2 2 2
Xanthomonas malvacearum (2A) O O O 0 2 2 3
- 20 -
.
' .
~$ ~
Composition #2 Tests
0 1 5 25 100 500 1000
Organisms Concentrations, parts per million_ __
Pythium ultimum (41B) O 0 1 2 2 2 2
Rhizoctonia solani (lD) O 0 1 2 2 2 2
Fusarium (4A) O 0 1 1 1 2 2
Fusarium (4D) O 0 1 1 2 2 2
Fusarium roseum (4C) O 0 2 2 2 2 2
Colletotrichum gossypi (35A) O O 0 2 2 2 2
Xanthomonas malvacearum (2A) O O 0 1 1 2 2 `
100 200 500 1000 2000
Concentrations, parts per million
Aspergillis sp. - O - O
Helminthsporium oryzae - - - O - 2 2
Mucor mucedo - - - O
Penicillium sp. - - - O
Rhizopus sp. - - - O
It is within the scope of this invention to modify the
disclosed compositions to improve performance or alter physical
properties to meet the needs of specific end uses. For example,
in addition to varying the relative amounts of materials used,
modifications For speciFic end uses can be made as by adding
thixotropes, cleansing agents, detergents, soil anti-redepositing
agents, film-forming agents, and other useful additives.
At high concentrations of use dilution, some ~f the
compositions of the invention, particularly the aryl sulfonic acids,
exhibit skin irritation, but it has been found that this can
largely be prevented by variously incorporating minor amounts of
a polyvinyl pyrrolidone or a nonyl phenol-ethylene oxide product
in the compositions of this invention.
Discoloration of substrates may occur, but this frequently
can be avoided by contacting the treated substrate, such as wood,
with a water solution of monoammonium phospha-te. Darkening may
also occur from a chemical reaction, as with iron, and corrosive
inhibitors may usefully be included in the compositions of this
invention.
- 21
