Note: Descriptions are shown in the official language in which they were submitted.
2075303
. ~0 92103047 PCT/GB91/01413
- 1 -
P~STICIDAL F0RMVLATIONS
The present invention relates to formulatlons, particularly pesticidal
formulations which contain two incompatible pesticides, to ~ethods for
making such formulations and their use in controlling pests.
It has been found that an anhydrous for~ulation of a pesticide, i.e.
one which does not contain an aqueous phase, may be formulated with a
second immiscible phase which contains a second pesticide. This has
the advantage that incompatible pesticides may be incorporated in the
same formulation.
Accordingly, the present invention provides a two-phase formulation,
the first phase of which comprises a first active ingredient, a stabi-
liser, and optionally an emulsifier or wetting or dispersing agent,
and a carrier or solvent for the active ingredient; and a second phase
immiscible with the first phase which comprises a second active
ingredient and optionally an emulsifier or wetting or dispersing agent
and a carrier or solvent for the second active ingredient.
Normally, the first active ingredient is dissolved or dispersed into
the first phase but when the active ingredient is a liquid a solvent
is not always required. The second phase which is immiscible with the
first phase contains the second active ingredient either dissolved or
dispersed in the-second phase. Preferably, the first phase is a water
i~miscible phase and the second phase is a water phase.
The first and second active ingredients are preferably physically
and/or chemically incompatible when contained in a single phase, i.e.
the presence of one of the actives in a formulation normally affects
adversely the stability or utility of the other active. In addition,
the active ingredient in the first phase may be one which has
properties, for example irritancv or noxious vapour, which may be
avoided by formulating it according to the present invention. Thus,
it may have been possible previously to prepare stable but irritant
.
W O 92/03W7 2 U 7 5 3 0 3 PCT/~B91/0141~
formulations of the active ingredients; formulations according to the
present invention may avoid such irritancy. By active ingredient we
mean both non-biologlcally and biologically active compounds. For
example, the aceive ingredlents may be selected from insecticides,
acarlcides, herblcldes, fungicldes, insect and plant growth
rsgulators, pheromones, insect behaviour modifiers, biological control
agents (e.g. viruses, bacteria and eggs of parasites), dyes, perfumes,
flavours, bactericides, lubricants, medicaments, food supplements,
paints, polishes, lacquers (including hair lacquer), textile
treatments (including sizes), or other active ingredients which are
limited in their use by their incompatibility with other active
ingredients. Examples of incompatible actives include combinations of
pesticldes selected from arthropodicides (insecticldes, acaricides),
herbicides, fungicides or insect and plant growth regulators.
Exa~ples of incompatible pesticides are the pyrethroids and
organophosphate insecticides, the pyrethroid and formamidine
insecticides, ~-cyano-pyrethrold insecticides and thiazole
anthelmintics, and pyrethroids and tributyl tin fungicides.
Examples of pyrethroid insecticides include those of the formula ~I)
x O
11
f ~o c-P.
~ ~ ~ (I)
where R is / Z
C~-C
\~ ~ L
/\
CN3 C~3
207~303
NO 92/03~47 PCT/GB91/01413
- 3 -
r\
or t~ R~
~C`'~
: R
and n ls 0 or 1,
Rl is halo, CF3 or CHF2O, R2 is hydrogen or halo, and Z and zl are
each independently selected from halo, CF3 and methyl, X is hydro~en
or halo, and X is H, CN or C~CH
,
C H O ~y~\~
--o~_C--CrzCrz{~
~,.,~,
Examples of pyrethroids are 3-phenoxybenzyl-(lRS)-cis,trans-3-(2,2-
dichlorovinyl-2,2-di- methyl- cyclopropane-l-carboxylate (permethrin),
: (RS)-a-cyano-3-phenoxybenzyl-(lRS)-cis,trans-3-(2,2-dichlorovinyl)-
2,2-dimethylcyclopropane-1-carboxylate (cypermethrin) and its indivi-
~,' ` .
', ',: .
'. ' '.
.~, . .
:
20753~3
W O 92/03W7 PCT/CB91/01413
- 4
dual lsomers such as the (lRS) cis lsomer (alphamethrin),
(S)-~-cyano-3-phenoxybenzyl-(IR)-çL~-3-(2,2-dibromovinyl)-2,2-dimethyl
cyclopropane-l-carboxylate (deltamethrin), or a reaction mixture
comprising two enantiomeric palrs in approximately ratio 2:3
(S)-o-cyano-3-phenoxybenzyl-(IR)-çl~-3-(2,2-dichlorovinyl)-2,2-dimeth-
ylcyclopropanecarboxylate and (R)-~-cyano-3--phenoxybenzyl (IS)-cis-3-
(2,2-dichlorovlnyl)-2,2-dlmethylcyclopropanecarboxylate with (S)-~--
cyano-3-phenoxybenzyl (IR)-trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-
cyclopropanecarboxylate and (R)-~-cyano-3-phenoxybenzyl(IS)-trans-3-
(2,2-dichlorovinyl)-2,2--dimethylcyclopropanecarboxylate (beta-cyper-
methrin), (RS)-~-cyano-3-phenoxybenzyl-(Z)-(IRS)-cis-3-(2-chloro-3,3,-
3-trifluoro propenyl)-2,2-dimethylcyclopropanecarboxylate (cyhaloth-
rin) and a mixture of its (S)(Z)-(IR)-cis and (R)(Z)-(IS)-cis-iso-
mers;
(RS)-o-cysno-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate
(fenvalerate) and the single (S), (S) isomer (esfenvalerate)
(RS)-~-cyano-3-phenoxybenzyl (5)-2-(4-difluoromethoxyphenyl)-3-methyl
butyrate (flucythinate), (RS)-~-cyano-3-phenoxybenzyl N(2-chloro-
u,o,u-trifluoro-p-tolyl)-D- valinate (fluvalinate), (RS)-o-cyano-4-
fluoro-3-phenoxybenzyl(IRS)-cis-trans-3-(2,2-dichlorovinyl)-2,2-di-
methylcyclopropanecarboxy late (cyfluthrin), (RS)-~-cyano-4-fluoro-3-
phenoxybenzyl(IRS)-cis-trans-3-(2-chloro-2(4-chlorophenyl)vinyl)-2,2-
dimethylcyclopropanecarboxylate (flumethrin), 2-methylbiphenyl-3-yl-
methyl(Z)-(IRS,3RS)-3-(2-chloro-3,3,3-trifluoroprop-l-enyl)2,2-dimeth-
yl cyclopropane carboxylate (Bifenthrin);
the allethrins, for example (lRS)-3-allyl-2-methyl-4-oxocylopent-2-
enyl (lR,3R)-2,2-dlmethyl-3-(2-methylprop-l-enyl)cyclopropanecarboxy-
late (bioallethrin), (lS)-allyl-2-methyl-4-oxocyclopent-2-enyl (lR,-
3R)-2,2-dimethyl-3-(2-methylprop-l-enyl)cyclopropanecarboxylate (S-bi-
oallethrin), and mixtures of allethrin isomers (esbiothrin);
the resmethrins, for example 5-benzyl-3-furylmethyl(IRS, 3RS; IRS,
3SR)-2,2-dimethyl-3-(2-methyl-prop-l-enyl)cyclopropanecarboxylate
(resmethrin) and 5-benzyl-3-furylmethyl (lR,3R)-2,2-dimethyl-3-(2-
methylprop-l-enyl)cyclopropanecsrboxylate (bioresmethrin).
- 207~3~3
W O 92/03047 PCT/GB9l/~1413
- 5 -
Examples of organophosphate insecticides are:
0,0-dimethyl-0-3,5,6-trichloro-2-pyridylphosphorothioate (Chloropyri-
fos-methyl)
Examples of formamidine insecticides include N-methyl bis(2,4-xylyl-
aminomethyl)amine (Amitraz). Examples of thiazole anthelmintics
include 2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]thlazole(levamisole).
Examples of fungicides include tributyl tin oxide.
Particularly preferred examples of incompatible actives in the
formulations of the present invention include deltamethrin and
chlorpyrifos methyl in an aqueous system.
Ihe f{rst phase is preferably dispersed within the second phase. The
stablliser forms a barrier at the interface between the dispersed
first phase and the second phase. The stabiliser is preferably a
film-forming alkanol eg. an alkanol which can act as an evaporation
retardsnt in an aqueous spray system as described in European Patent
Speclfication 331474. It is preferably a primary alcohol; preferably
wlth no more than one or two side substitutions selected from methyl,
ethyl, trifluoromethyl and halo (e.g. fluoro or chloro), with such
substitutions preferably remote from the alcohol group (preferably at
least 7 carbon atoms away from the hydroxyl group), and preferably the
alkanol is not substituted st all; preferably C16 20; preferably
saturated; and preferably a solid at 27C, Octadecan-l-ol and,
particularly, hexadecan-l-ol are preferred. Hexadecan-l-ol (also
known as cetyl alcohol) is usually available commercially as a mixture
with a minor propor~ion of octadecan-l-ol (stearyl alcohol) and such
"cetostearyl alcohol" is quite satisfacto~y. Heptadecan-l-ol performs
adequately but is much more expensive. Other highly effective
film-forming agents include l-hexadecylamine, l-heptadecylamine and
l-octadecylsmine. Less preferred film-forming agents include
hexadecan-2-ol, 1,2-hexadecandiol, methyl stearate, stearyl acetate,
methyl palmitate and 1,2-octadecandiol. N-alkoxyalkanols may be used,
2~753~3
W O 92/03047 . PCT/Gn91/01~13
- 6 -
( 2)210C2H40H, CH3(CH2)2l0c3H6oH~ C~3(cH2)l7oc2H4oH or
CH3(CH2)l50C2H40H, as may oxyethylene-docosanol and mixtures of any of
the said film-forming compounds.
The emulslfier may be any suitable compound or mixture of compounds.
Cationic emulsifiers can be used, but they tend to irritate the user's
eyes. AnionLc emulsifiers such as calcium dodecyl benzene sulphate
(CDBS) or sodium d-isopropyl naphthalene sulphonate (SDNS) can also be
used, but these are not as effective at stabilising the emulsion
whilst maintaining evaporation recarding properties. Preferably, the
emulsifler is a non-ionic compound, or mixture of non-ionic compounds,
having an HL~ (hydrophilic/lipophllic balance) of 6-20 and preferably
8-18. Suitable compounds include polyoxyethylene stearyl ethers
(PSE), polyoxyethylene monolaurates (PEM), polyoxyethylene
mono-oleates (PMO), sorbitan mono-oleate (SMO), nonylphenol ethoxylate
(NPE), polyethylene glycol (PEG) and blends of oleyl ethoxylate (10
mole), and PEG20 glyceryl oleate (OE/PGO).
These emulsifiers are available as follows:
Abbrev. Trade name Suoplier
OE/PGO Tegoplant Th.
EMll Goldschmidt
Ltd.
PSE Bri; 72, Brij 76, ICI Speciality
Bri~ 78 Chemicals
PEM Tween 20 ICI Speciality
Chemicals
SMO Span 80 ICI Speciality
Chemicals
PMO Tween 80 ICI Speciality
Chemicals
., ~; ~ . . .
207~3~3
W O 92/03W7 PCT/CB91/0141
- 7
NPE Ethylan Lankro
KEO,55,BV Chemicals
; Limited
CD~S Arylan CA Lankro
Chemicals
Limited
: SDN Aerosol OS Cyanamid GB
~, ~ Ltd.
:- The solvent, for the first phase, preferably has a low relative
molecular mass, namely less than about 200. Suitable compounds
include aromatic hydrocarbons, lower alkyl esters, lower ketones,
lower alkanols and lower alksnes, the term n lower" ~eaning Cl 12
: preferably Cl 10 and more preferably Cl 8
, ; Particular solvents include the following, all available from Exxon
. Chemicals Llmited;
,. .
~ "Solvesso 150n - An aromat$c hydrocarbon solvent (C9 to Cll) with a
: distillation range 190 to 210C.
"Solvesso 200n - An aromatic hydrocarbon solvent (C10 to C12) with a
- distillation range 226 to 290C.
nExxate 700n - Heptyl acetate 99~ pure, or
Odourless kerosene - A mixture of high boiling non-aromatic
,: hydrocarbons consisting of paraffins and naphthenes with a
- distillation range of 180 to 270C.
She first phase may comprise more than one active ingredient
. . (optionally with a synergist or potentiator, which is regarded as an
: active ingredient for the purpose of the Formula below), more than one
solvent, more than one emulsifier and/or more than one stabiliser,
togeeher vi~h D~her lngredLen~s such as perLu=es and dyes.
';
. .
.
.
2075303
., WO 92/03047 PCl /~ B9 1/01413
- 8
"
In A preferred aspect, the first phase of the formulation satisfies
the formula :
mass of o~l DhAse s oil X ~xp ~ /4)+~ ln(AX ~]
mass of stabiliser Mstabiliser C
~,
where L i9 less than or equal to lS, ~ - 700376, B - -1.51, C - 0.8472
oil is the weighted average relative molar mass of the oil phase
~stabiliser is the average molar mass of the stabiliser, and
X - ( oil)l'8
:~ Y
,:
where Y is the molar solubility ratio of the formulation, defined as
the minimum number of moles of oil phase which will dissolve the
stabiliser, divided by the number of moles of stablliser, provided
that, in the Formula above, any solvent which has no liquid phase at
27 C at atmospheric pressure is excluded.
The "oil phase" is the liquid non aqueous phase and will comprise one
or more of the active ingredient, the solvent therefor and in so~e
cases the emulsifier.
For the avoidance of doubt, and to clarify any ambiguities which may
arise in the printing or copying of this specification, it is to be
noted that the relational symbol in the Formula is n less than or equal
to", ~Exp" means the exponential of what follows in brackets, "ln"
means the natural logarithm, i.e. log , L is divided by 4, X is raised
to the power B, B is a negative value ~minus 1.51) and, in the
definition of X, Moil is raised to the power 1.8.
Preferably L is less than 12, 10, or 8 and is most preferably less
than 5. A distilled water spray has an "L" value of about 26, and
most conventional diluted formulations have a value of about 22-30.
W O 92/03047 2 0 7 ~ 3 0 ~ PCT/GB9l/0l4l3
: - 9 -
In the formulations of the invention, "L" can be set at a desired
value in order to calculate the required ratios of the ingredients.
Hoil, the aversge moleculsr welght of the oil phase, ls the weighted
aversge, i.e. taking into account the relative proportions of the
ingredients.
The value ~yn, namely the molar solubility ratio of the formulation,
may be derived empirically by making up at 40C a series of mixtures
wlth different ratios of oil phase to alkanol, allowing the mixtures
to cool to 27C, leaving the cool mixtures for at least 48 hours at
27 C, snd determining the amount, in moles, of the oil phase which is
needed to dissolve completely a given amount of retardant, in moles.
- The former is then divided by the latter to give Y.
Preferred film-forming compounds include C16 20 saturat
such 8S hexadecan-l-ol and C16 18 saturated amines.
Preferred emulsifiers and solvents for the first phase are as
described hereinbefore for European Patent Specification 331474, which
is incorporated herein by reference.
~'
.~ The use of the formulations of the present invention will be dependent
upon the nature of the active ingredients included within the
-~. formulation but the formulations will commonly be used to control
pesticidal infestations such as insec~, acarine or helminth or
. microbial infestations. The application rate of the active
:. ingredlents will correspond to the application rates of these actives
when applied conventlonally for that particular use.
:
: A preferred formulation of the present invention contains 20~
- chlorpyrlfos methyl and 1% deltamethrin, cetyl alcohol being the
stabiliser. This formulation is useful for the treatment of stored
crops such as grain, in particular against insect pests, of the orders
Coleoptera (e,g. Anobium, Ceutorh~nchus, Rhvnchophorus, Cosmo~olites,
2075~
W O 92/03047 PCT/GB91/01413
- 10 -
Lis5s~hQ~trus, Mell~ethes, ~YpothlLemus, Hvlesinus, AcalYmma, Lema,
PsYlllodes, Lept~notsrsa, Gonocephalu~, Agrio~es, Dermolepida,
HeteronYchus, Phaedon, TrlbQliu_, Sltophilus, OrYzaephilus,
RhYzoDertha, Proste~hanus, CrYp~oletes, Trogode~a, Tvpheae,
Dlab~otlca, ~nh_nomus or Anth~enus spp.), Lepidoptera (e.g EDhestia,
Mamestra, ~arlas, Pectinophora, Ostrl~la, TrichoDlusia, Pieris,
Plodia, Sltotroga, CorcYra, LaphYgma, Agrotls, Amathes, Wiseana,
TrvDorvsa, piatrae, SDorganothls, CYdia, Archips, Plutella, Chilo,
Hellothis, Spodoptera or Tineola spp.), Diptera (e.g. Musca, Aedes,
AnoDheles, Culex, Glossina, Simulium, Stomoxys, Haematobia, Tabanus,
Hyd~otaea, Lucilia, Chrvsomia, Callltroga, Dermatobia, Gasterophilus,
HYpoderma, HvlemYia, Atherigona, Chlorops, PhvtomYza, Ceratitis,
Liriomy~ and Melophaeus spp.), Phthiraptera (Malophaga e.g. Damalina
spp. and AnoDlura e.g. Linogna~hus and HaematoDinus spp.), Hemiptera
(e.g. ADhis, Bemisia, Phorodon, Aeneolamia, Empoasca, Parkinsiella,
Pyrilla, Aon~diella, Coccus, Pseudocoçus, Helopeltis, LYgus,
~y~dercus, OxYcarenus, Nezara, Ale~urodes, Triatoma, Psvl~a, MYSUS,
Megoura, P~hYlloxera, Adelves, Nllo~arvata, Nephrotetlx or Cimex spp.),
Orthoptera (e.g. ocusta, Gryllus, Schistocerca or Acheta spp.),
Dlctyoptera (e.g. 31attella, Per~planeta or Blatta spp.) Hymenoptera
(e.g. Athalia, Cephus, ~ , Solenopsis or Monomorium spp.), Isoptera
(e.g. Odontotermes and Reticulitermes spp.), Siphonaptera (e.g.
Cte~çephalides or Pulex spp.), Thysanura (e.g. Lepisma spp.),
Dermaptera (e.g. Forficula spp.), Pscoptera (e.g. PeriDsocus spp.) and
Thysanoptera (e.g. ThriDs tabaci),. Acarine pests include ticks, e.g.
members of the genera Boophilus, Ornithodorus, Rhipicephalus,
Amblvomma, HYalomma, Ixodes, HaemaDhYsalis, pe~macentor and Anocentor,
and mites and manges such as Aca~us, Tvrophagus, GlycvDhagus,
Tetranychu~, Psoroptes, Notoednes, Sarço~tes, Psorergates, ChorioDtes,
Eutromb~ _, Demodex, Panonvchus, Brvobia, Eriophves, Blaniulus,
poly~hagotarsonemus, Scutigerella, and Oniscus spp. and Periplaneta,
Blatta, Blattella and Lapisma.
:
- 207~303
W O 92/0304~ PC~/GB91/01~13
The formulations of the pregent invention may be prepared as follows:
1) The first actlve is dlssolved in a solvent to form, or is itself,
the first phase.
2) The stabiliser is dissolved into the first phase.
3) The second active ingredient ls dispersed in part of the second
phsse.
4) The suractsnts are dispersed either lnto the first phase or ineo
the part of the second phase containing the second active
ingredient.
S) The first phase is then dispersed into that part of the second
phase that does not contsin the second active ingredient.
: 6) The remainder of the second phase containing the second active
ingredient is mixed with the mixture of the first phase and the
other part of the second phase.
Step (6) is not carried out under high sheer conditions.
Therefore the second portion of the second phase simply combines
.with the first portion of the second phase and the end result is
a first-phase-in-second-phase dispersion or emulsion.
The present invention will now be described in more detail by way of
the ~ollowing examples. Example 1 describes formulations according to
the present invention containir.g pyrethro~d and an organophosphorus
insecticide. Example 2 shows the result of tests to demonstrate the
stability of formulations according to the present invention. Example
3 shows the results of biological tests on various insect pests.
1 2a7a333
` W O 92/03047 . PCT/CB91/01413
j. - 12
~xam~Le L Formulstions
Ingredients ~ wJw
.i chlorpyrifos methyl 19.lS
solvesso 150 l9.lS
water (deionised) 51.40
emulsifiers 2.00
Deltamethrln (20~ SC) 5.20
The deltamethrin ~20~ SC) contains deltamethrin (20~) in wa~er with
surfactant, thlckening agents and biologlcal preservative.
The oil phase was prepared by dissolving cetyl alcohol in a solution
of chlorpyrifos methyl in Solvesso 150 at a temperature up to 50C.
The emulsifiers were added to the water at 60C and the resultant
aqueous solution cooled to 50C (aqueous phase).
The oil phsse was added to the aqueous phase at 50C with vigoro~s
mixing and the resultant emulsion cooled to 20C.
A 20~ aqueous suspension of deltamethrin was added with stirrlng at
20-25C
r Example 2 - Stabillty testing
Tests were carrled out on the stability of active ingredients in a
- formulation according to the present lnvention (A) and in a two-phase
ormulation that does not contain stabiliser (B).
Ltlon A Results
. ~ A chlorpyrifos methyl/Deltamethrin Formulation with film forming agent
was prepared in a similar manner to Example l above.
Typical Stability Data: chlorpyrifos methyl (CPMe) tests (figures +
104)
',~
. .
.
~ ~ W 0 9~/03047 20753~3 PCT/c~391/0141~
Time ln months 25 C 38 C 50 C
. (M)
Initlal 100100 100
~,
3 M or 4 M 101103 103
~ 6 H 102100 103
r
. ~ 12 M 10194 101
'' ~ Typical Stabillty Data : Delta~ethrin (DLTM)
; Time in months 25 C 38 C 50 C
(M)
:. Inltial 100100 100
.'' ' ' .
: : 3 M or 4 M 96 99 98
6 M 97 103 103
,,., ~ .
~. 12 M 98 94 76
~i":'.'',
. FormulatiQns_B - results
~ ~ A chlorpyrifos methyl/Deltamethrin Formulation without film forming
:y: agent.
.- Typical Stabillty Dsta : CPME
Time in months 25 C 38 C 50 C
,. (M)
. : Inltial 100 100 100
.,
3 M 112 106 71
'
/
207~30~
W O 92/03047 PCT/GB91/01413
- 14 -
Typical StabilLty Data : DLTM
TLme in months 25C 38C 50C
(M)
Initlal lO0lO0 lO0
3 M 7575 16
The results show formulations (B) without film forming agent are
" relatively unstable.
Exa,,m"p~ Biological ,,testi~g
Protocol: Appropriately water-diluted formulation was sprayed on to
- 400 tonnes of grain at Wail, Victoria. It was applied to the grain
' , stream during turning at one litre spray per tonne. Treated grain was
,'~ sampled at lntervals by means of a vacuum probe. Bioassays were
, conducted by holding lO0 adult insects on 150g or 300g grain. After 3
" weeks incubation at 25C, 55-60~ relative humidity the insects were
sieved off and mortality counted. The grain was further sieved at 7,
9, and ll weeks to remove and mortality count adult progeny.
Ç ~ (1) 0.24:4.9mg~kg deltamethrin:chlor~yrifos-methYl
: .
,~ Insects Months of 4 Progeny Progeny
; tested post-treatment Mortality numbers suppression
storage living dead
'-
Sitophilus 0 lO0 0 4 99.8
oryzae l.5 lO0 0 0 lO0
3 lO0 0 0 lO0
4.5 lO0 0 0 lO0
6 lO0 0 0 lO0
9 100 0 0 100
,
W O 92/03047 2 0 7 5 3 ~ 3 PCT/GB91/01413
Rhyzoperthn O 100 O 0 100
domlnlcs 1.5 100 O O 100
3 100 O O 100
4.5 100 O O 100
6 100 O O 100
9 100 0 0 100
Trlbolium O 100 O O 100
. castaneum 1.5 100 O 1 99.7
. 3 100 O O 100
4.5 100 O 1 99.5
6 100 O 4 99.0
9 100 O 0 100
: Queensland O 100 O O 100
. Tribolium 1.5 100 O 2 97
castaneum 3 99 0 O 100
279 4.5 99 O 1 99.7
6 100 O 4 99.0
9 95 0 O 100
Oryzaephilus O 100 O O 100
: surinamensis 1.5 100 O O 100
3 100 O 2 99.7
4.5 99 O O 100
6 95 O 1 99.9
9 100 0 0 100
Results show good control of insect pests for post-treatment storage
up to 9 months.
:
