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`US 20020114821Al
`
`(19) United States
`(12) Patent Application Publication
`Lescota et al.
`
`(10) Pub. No.: US 2002/0114821 Al
`Aug. 22, 2002
`(43) Pub. Date:
`
`(54) PESTICIDAL FORMULATION
`
`(76)
`
`Inventors: Regina D. Lescota, Belmar, NJ (US);
`Pradip K. Mookerjee, Flemington, NJ
`(US); John Misselbrook,
`Southhampton (GB); Robert F.
`Peterson JR., Abington, PA (US)
`
`which is a continuation of application No. 08/744,
`809, filed on Nov. 6, 1996, now abandoned.
`
`(60) Provisional application No. 60/006,346, filed on Nov
`8, 1995.
`
`Publication Classification
`
`Correspondence Address:
`MERCK AND CO INC
`PO BOX2000
`RAHWAY, NJ 070650907
`
`(21) Appl. No.:
`
`09/963,113
`
`(22) Filed:
`
`Sep.25,2001
`
`Related U.S. Application Data
`
`(60) Division of application No. 09/318,111, filed on May
`25, 1999, which is a continuation of application No.
`09/146,463, filed on Sep. 3, 1998, now abandoned,
`
`(51)
`
`Int. CI.7 ……………………. AOlN 57/18; AOlN 37/00;
`AOlN 25/08
`(52) U.S. Cl. ……………………… 424/409; 504/206; 504/320
`
`(57)
`
`ABSTRACT
`
`The present invention is directed to a pesticidal composition
`of a water-soluble pesticide and processes for its manufac(cid:173)
`ture. More specifically, the invention relates to a soluble
`granule (SG) pesticidal formulation comprising a water(cid:173)
`soluble pesticide and a water-soluble filler. The present
`invention provides a pesticidal formulation with efficacy
`equal to the corresponding liquid formulation, yet with
`improved handler safety, such as lower eye irritation
`
`1
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`PESTICIDAL FORMULATION
`
`FIELD OF THE INVENTION
`[0001] The present invention relates to pesticidal compo(cid:173)
`sitions comprising a water-soluble pesticide and process for
`their manufacture. More specifically, the invention relates to
`soluble granule (SG) formulations comprising a water(cid:173)
`soluble pesticide and a water-soluble filler.
`
`BACKGROUND OF THE INVENTION
`[0002] Emulsifiable concentrate (EC) agricultural formu(cid:173)
`lations of pesticides are well known in the art. These
`formulations generally comprise emulsifying and dispersing
`agents in addition to the pesticide to give a uniform solution.
`However, these agricultural formulations suffer numerous
`drawbacks because they are liquid. In particular, liquid
`pesticidal formulations must be handled carefully to mini(cid:173)
`mize safety concerns, particularly dermal and ocular irrita(cid:173)
`tion.
`
`[0003] Although solvent-free pesticidal compositions are
`known, most solvent-free pesticidal formulations have lower
`bioactivity than the corresponding emulsifiable concentrate
`formulations. Thus, one skilled in the art frequently has been
`forced to choose between using a solvent to give a more
`bioactive formulation but with higher dermal and ocular
`toxicity, or having a less active solid formulation.
`
`[0004] The present invention overcomes the drawbacks of
`liquid formulations by taking advantage where possible of
`the water solub山ty of the pesticide to furnish a composition
`in divided form so that it will dissolve in water.
`
`[0005] Certain methods for preparing water-soluble gran(cid:173)
`ules of pesticides are known in the art. PCT Publication No.
`WO 90/12503 discloses the formation of alkaline salts of
`soluble acidic or phenolic pesticides to give a granular
`composition. U.S. Pat. No. 4,511,395 discloses wettable
`herbicidal powder compositions which comprise a swelling
`hydrous silicate clay. EPO Publication No. EP 0,111,112
`discloses pesticide granules comprising an inert carrier and
`a pesticide, and which are coated with finely divided silica.
`
`[0006] The use of lactose as a solid filler to make tablets
`is well known in the pharmaceutical industry. (See e.g. Lerk,
`C. F., "Consolidation and Compaction of Lactose"Drug
`Development and Industrial Pharmacy, 19, 2359 (1993);
`"Role of Ingredients and Excipients in Developing Pharma(cid:173)
`ceuticals"Manufacturing Chemist, p. 32 (April 1994). Nev(cid:173)
`ertheless, the use of lactose or other water-soluble fillers as
`agricultural inert ingredients is not common in formulating
`pesticides for crop protection. Hudson and Tarwater (Reduc(cid:173)
`tion of Pesticide Toxicity by Choices of Formulation, J. L.
`Hudson and 0. R. Tarwater, inACS Symposium series #371,
`Pesticide Formulations, B. Cross and H. B. Scher, eds.)
`discuss the effect the choice of formulation on toxicity, and
`state (on p. 129) that the ocular irritation can be very
`different for different formulations of the same active ingre(cid:173)
`dient, and that changes in the other toxicity categories may
`occur. Nevertheless, they do not discuss how such dimin(cid:173)
`ished toxicity may be achieved. Furthermore, they mention
`wettable powders (WP), water dispersible granules (WDG)
`or dry flowables (DF), but they do not even mention soluble
`granule (SG) formulations.
`
`sponding liquid formulation of a given pesticide. Because it
`is a solid, the SG formulation exhibits improved ease of
`handling relative to the liquid formulation. Nevertheless,
`when dissolved in water the SG formulation provides a clear
`solution which is aesthetically pleasing. The SG formulation
`also minimizes the use of ingredients of environmental
`concern by eliminating the need for volatile organic com(cid:173)
`pounds and employing fillers which are biologically derived,
`thereby diminishing the potential environmental impact. In
`add山on, formulations of higher concentration (hence lower
`cost per kg of active ingredient formulated) can be achieved
`without any loss in biological activity with respect to a liquid
`formulation. Because the dried granules in the SG formu(cid:173)
`lation are of roughly constant bulk density, the granules may
`be measured by volume, thus making them equally conve(cid:173)
`nient to liquid formulations in ease of use.
`
`[0008] _More importantly, however, use of the instant SG
`formulat10n is less risky to personnel than the corresponding
`liquid formulation. Risk of exposure is generally evaluated
`under the guide: risk=hazardxexposure. Because the instant
`SG formulation is less toxic, the hazard is decreased. In
`addition, the probability of contact is lower when the mate(cid:173)
`rial is in a solid rather than a liquid form and hence the
`degree of exposure is also reduced. The present invention
`also affords relatively hard non-dusty granules, thereby even
`further diminishing the risk of exposure to dust from the
`composition. Also, the present invention may be practiced
`without the use of mineral fillers which contain crystalline
`silica, a known carcinogen. Thus, the present invention
`diminishes the risk of exposure and provides greater handler
`safety, especially with regard to ocular irritation, than a
`liquid formulation.
`
`[0009] Accordingly, the present invention provides a rela(cid:173)
`tively safe, bionatural delivery system for a pesticide which
`is water soluble at the concentration at which it is employed.
`
`SUMMARY OF IBE INVENTION
`
`[0010] The present invention relates to a pesticidal com(cid:173)
`position of a water-soluble pesticide and processes for its
`manufacture. More specifically, the invention relates to a
`soluble granule (SG) pesticidal formulation comprising a
`water-soluble pesticide and a water-soluble filler. The
`present invention provides a pesticidal formulation with
`efficacy equal to the corresponding liquid formulation, yet
`with improved handler safety, such as lower eye irritation
`
`DETAILED DESCRIPTION OF THE
`INVENTION
`[0011] The present invention is directed to an pesticidal
`composition comprising a water-soluble pesticide and pro(cid:173)
`cesses for its manufacture. More specifically, the invention
`relates to a soluble granule (SG) formulation comprising a
`water-soluble pesticide, such as emamectin benzoate, and a
`water-soluble filler, such as lactose.
`
`[0012] The pesticidal composition of the present invention
`comprises: a water-soluble pesticide; and a water-soluble
`filler.
`
`[0013] The present pesticidal composition may further
`comprise: a wetting surfactant; and/or a dispersing surfac(cid:173)
`tant. Optionally, a defoaming agent may also be present
`
`[0007] The soluble granule (SG) formulation of the
`present invention has numerous advantages over the corre-
`
`[0014] Preferably the water-soluble pesticide is selected
`from: emamectin or an agriculturally acceptable salt thereof.
`
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`Preferably the water-soluble filler is selected from: lactose,
`sucrose, glucose, and the like. Preferably the wetting sur(cid:173)
`factant is selected from: sodium N-methyl-N-oleyl taurate,
`sodium N-methyl-N-palmityl taurate, sodium N-methyl-N(cid:173)
`oleoyl taurate, sodium dioctyl sulfosuccinate and other
`sodium alkyl sulfosuccinates, sodium lauryl sulfate, alpha(cid:173)
`(p-nonylphenyl)-omega-hydroxy poly(oxyethylene) with an
`average of 8-12 moles of ethylene oxide, and alpha-(p(cid:173)
`octylphenyl)-omega-hydroxy poly(oxyethylene) with an
`average of 7-12 moles of ethylene oxide. Preferably the
`dispersing surfactant is selected from: sodium alkyl naph(cid:173)
`thalene sulfonate, sodium napthalene sulfonate, calcium
`lignosulfonate, sodium
`lignosulfonate, and ammonium
`lignosulfonate. Preferably the defoaming agent is selected
`from: methylated silicones, polyorganosiloxane, and 2-eth(cid:173)
`ylhexanol.
`
`[0015] More preferably the water-soluble pesticide is ema(cid:173)
`mectin or emamectin benzoate. More preferably the water(cid:173)
`soluble filler is lactose. More preferably the wetting surfac(cid:173)
`tant is sodium N-methyl N-oleyl taurate. More preferably
`the dispersing surfactant is sodium alkyl naphthalene sul(cid:173)
`fonate. More preferably the defoaming agent is polyorga(cid:173)
`nosiloxane.
`
`[0016] The pesticidal composition of the present invention
`may be provided in the form of a wettable powder but
`preferably is in the form of a water-soluble granule. Simi(cid:173)
`larly, the pesticidal composition of the present invention
`may be provided as an aggregate, a matrix, or a monolith,
`such as a brick, pellet, tablet, stick, film, sheet, and the like
`Preferably, the pesticidal composition of the present inven(cid:173)
`tion is embedded in a water-soluble matrix or monolith. It
`also will be appreciated by one skilled in the art that the
`present invention further includes encasement of the instant
`pesticidal compositions in a water-soluble package, such as
`a pouch, sachet, bag, capsule, and the 1出e
`
`[0017] The pesticidal compositions of the present inven(cid:173)
`tion comprise 0.1 to 90% by weight of a water-soluble
`pesticide, preferably emamectin benzoate; and 30 to 99.9%
`by weight of a water-soluble filler, preferably lactose (not to
`the exclusion of other ingredients).
`
`[0018]
`It will be appreciated by one skilled in the art that
`the sum of the proportions of the water-soluble pesticide and
`the water-soluble filler are not greater than 100% by weight
`and that the exact concentrations of the components may
`vary depending on the presence of impurities
`
`In a more preferred embodiment, the pesticidal
`[0019]
`compositions of the present invention comprise 0.1 to 60%
`by weight of a water-soluble pesticide, preferably emamec(cid:173)
`tin benzoate; 40 to 99.9% by weight of a water-soluble filler;
`0 to 50% by weight of a wetting surfactant; 0 to 50% by
`weight of a dispersing surfactant; 0 to 5% by weight of a
`defoaming agent (not to the exclusion of other ingredients).
`
`[0020]
`It will be appreciated by one skilled in the art that
`the sum of the proportions of the water-soluble pesticide, the
`water-soluble filler, the wetting surfactant, the dispersing
`surfactant and the defoaming agent are not greater than
`100% by weight and the exact concentrations of the com(cid:173)
`ponents may vary depending on the presence of impurities
`
`In one embodiment of the present invention the
`[0021]
`formulation contains about 0.1 to 90% by weight of the
`water-soluble pesticide.
`
`~0022]_ Preferred pesticidal compositions of the present
`mvent10n comprise 0.1 to 60% by weight of emamectin
`benzoate; 40 to 99.9% by weight of lactose; 0 to 25% by
`weight of sodium N-methyl N-oleyl taurate; 0 to 10% by
`weight of sodium alkyl naphthalene sulfonate; and O to 3%
`by weight of polyorganosiloxane (not to the exclusion of
`other ingredients).
`
`[0023] More preferred pesticidal compositions of the
`present invention comprise 1 to 50% by weight of emamec(cid:173)
`tin benzoate; 40 to 99% by weight of lactose; 0 to 10% by
`weight of sodium N-methyl N-oleyl taurate; 0 to 2% by
`weight of sodium alkyl naphthalene sulfonate; and O to 1 %
`by weight of polyorganosiloxane (not to the exclusion of
`other ingredients). Even more preferred pesticidal compo(cid:173)
`sitions are those which may comprise 1 to 20% by weight of
`emamectin benzoate.
`
`[0024] E ven more preferred pestlc1dal compos1t10ns of the
`present mvention comprise 1 to 20% by weight of emamec(cid:173)
`tin benzoate; 60 to 99% by weight of lactose; 5 to 10% by
`weight of sodium N-methyl N-oleyl taurate; 0.5 to 2% by
`weight of sodium alkyl naphthalene sulfonate; and Oto 0.5%
`by weight of polyorganosiloxane (not to the exclusion of
`other ingredients). Still more preferred pesticidal composi(cid:173)
`tions are those which comprise 1 to 10% by weight of
`emamectin benzoate.
`
`[0025]
`It will be appreciated by one skilled in the art that
`the sum of the proportions of emamectin benzoate, lactose,
`sodium N-methyl N-oleyl taurate, sodium alkyl naphthalene
`sulfonate and polyorgano-siloxane are not greater than
`100% by weight and that the exact concentrations of the
`components may vary depending on the presence of impu(cid:173)
`ntles.
`
`[0026] Especially preferred pesticidal formulations are as
`follows:
`
`[0027] Soluble granules comprising about 5.3% by weight
`of emamectin benzoate; about 86% by weight of lactose;
`about 7.5% by weight of sodium N-methyl N-oleyl taurate;
`about 1 % by weight of sodium alkyl naphthalene sulfonate;
`about 0.1 % by weight of polyorganosiloxane
`
`[0028] The present invention further includes a process for
`preparing a soluble granule formulation which process com(cid:173)
`pnses:
`
`(1) forming a powder blend of a water-soluble
`[0029]
`pesticide and a water-soluble filler;
`
`[0030]
`
`(2) adding water to the blend;
`
`(3) extruding the wet blend through a die to
`[0031]
`form granules; and
`
`[0032]
`
`(4) drying the granules to remove the water.
`
`[0033] The present invention is further directed to a
`soluble granule formulation prepared by such process
`
`In a preferred embodiment, the process for prepar(cid:173)
`[0034]
`ing a soluble granule formulation comprises:
`
`(1) forming a powder blend of a water-soluble
`[0035]
`pesticide, a water-soluble filler, a wetting surfactant
`and a dispersing surfactant;
`
`[0036]
`
`(2) adding water to the blend;
`
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`US 2002/0114821 Al
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`(3) extruding the wet blend through a die to
`[0037]
`form granules; and
`
`[0038]
`
`(4) drying the granules to remove the water.
`
`[0039] Optionally, in this process a defoaming agent may
`be added to the powder blend.
`
`[0040] The present invention is further directed to a
`soluble granule formulation prepared by such process
`
`[0041] Specifically exemplifying the present invention is
`the process comprising the steps of
`
`(1) forming a powder blend of a emamectin
`[0042]
`benzoate and lactose;
`
`[0043]
`
`(2) adding water to the blend;
`
`(3) extruding the wet blend through a die to
`[0044]
`form granules; and
`
`[0045]
`
`(4) drying the granules to remove the water.
`
`[0046] A preferred embodiment which specifically exem(cid:173)
`plifies the present invention is the process comprising the
`steps of:
`
`(1) forming a powder blend of a emamectin
`[0047]
`benzoate, lactose, sodium alkyl naphthalene sul(cid:173)
`fonate, sodium N-methyl N-oleyl taurate, and poly(cid:173)
`organosiloxane;
`
`[0048]
`
`(2) adding water to the blend;
`
`(3) extruding the wet blend through a die to
`[0049]
`form granules; and
`
`[0050]
`
`(4) drying the granules to remove the water.
`
`[0051] The present invention is further directed to a
`soluble granule formulation of emamectin benzoate pre(cid:173)
`pared by such process.
`
`[0052] The present invention is further directed to a deliv(cid:173)
`ery system for water-soluble pesticides, in particular, ema(cid:173)
`mectin benzoate, which comprises soluble granules and the
`use thereof.
`
`[0053] The present invention further provides a method
`for administering the water-soluble pesticide comprising
`
`(1) formulating the water-soluble pesticide as
`[0054]
`a soluble granule;
`
`(2) mixing with water a portion of the soluble
`[0055]
`granule sufficient to give the desired amount of
`active ingredient of the water-soluble pesticide; and
`
`[0056]
`
`(3) applying the pesticide/water mixture.
`
`[0057] The present invention is further directed to a pes(cid:173)
`ticide/water mixture prepared by such process.
`
`[0058] The application of the pesticide/water mixture may
`be conducted by methods well known in the art, including,
`spraying, misting, dripping, infusing, injecting, irrigating,
`and the like.
`
`[0059] The term "water-soluble pesticide" as used herein
`includes any biologically active pesticidal agent or crop
`protection chemical which is water soluble at the concen(cid:173)
`tration in which it is employed (i.e. the agent is water soluble
`at the volume used in field application). Such water-soluble
`pesticides include certain fungicides, herbicides, such as
`
`plant growth regulators, and insecticides, such as nemato(cid:173)
`cides, anti-helmentics, and miticides. Exemplary water(cid:173)
`soluble pesticides which may be employed in the present
`invention include: the fungicides: blasticidin-S, kasugamy(cid:173)
`cin, and hymexanol; the herbicides: acifluorfen, glyphosate,
`and glufosinate; the plant growth regulants: gibberellic acid,
`maleic hydrazide and dikegulac; and the insecticides: aceph(cid:173)
`ate, emamectin, and emamectin benzoate. A particularly
`preferred water-soluble pesticide is emamectin, or an agri(cid:173)
`culturally acceptable salt thereof, such as the salt formed
`with benzoic acid, salicyclic acid, gallic acid, benzene(cid:173)
`sulfonic acid, hydrochloric and citric acid, especially ema(cid:173)
`mectin benzoate. One skilled in the art will readily appre(cid:173)
`ciate that these pesticides exhibit sufficient water solubility
`that they will dissolve when mixed with water at the labeled
`use rate. For example, commercial label use rates of aceph(cid:173)
`ate are as high as 1.33 lb (0.60 kg) in a minimum of 3 gallons
`(11.4 liters) of water. Because 650 g of acephate is soluble
`in 1 liter of water, the acephate is fully soluble in water at
`its maximum label use rate. Similarly, emamectin benzoate
`is soluble at about 100 ppm in water. Thus, at a typical use
`rate 3.4 g of emamectin benzoate will be soluble in about 34
`liters of water.
`
`[0060] The term "water-soluble granule" as used herein is
`intended to include any granular or pelletized compositions
`which permit the active ingredient to be in solution after
`dissolving in water. It is not necessary for all of the ingre(cid:173)
`dients of the water-soluble granule to be in solution as long
`as the active ingredient itself is in solution. Thus, the present
`invention includes within its scope water-soluble granules in
`which some of the ingredients may be relatively insoluble.
`The actual physical form of the instant pesticidal composi(cid:173)
`tion is not critical to the proper function of the present
`invention.
`
`[0061] The term "water-soluble filler" as used herein
`includes any water soluble or water dispersible agent which
`may be employed to dilute the pesticide. Preferred water(cid:173)
`soluble agents include those which are biologically derived.
`Appropriate water-soluble fillers include lactose, glucose,
`fructose, mannose, mannitol, sucrose, such as confectioner's
`sugar, black sugar, brown sugar, soft brown sugar, other
`sugars or saccharides, microcrystal~ine cellulose, powdered
`cellulose, calcium phosphate(s), morganic water-soluble
`salts, and the like, and mixtures thereof. Examples of lactose
`which can be used in the present invention include hydrated
`a-lactose, anhydrous a-lactose, hydrated~-lactose, anhy(cid:173)
`drous~-lactose, and the like, and mixtures thereof.
`sur actants can be used as the surfactant m the
`f
`[0062] Any
`present invention, as long as it will emulsify the desired
`pesticide, or the pesticide when mixed with water. Examples
`of such surfactants include glycerine fatty acid esters,
`sucrose fatty acid esters, sorbitan fatty acid esters, fatty acid
`salts, alkyl sulfates, alkylbenzene sulfonic acid salts, alkyl
`aryl ethers and polyoxyethylenated products thereof, ethyl(cid:173)
`ene oxide addition products of higher alcohols, polyoxyeth(cid:173)
`ylene polyoxypropylene glycol, lignin sulfonic acid salt,
`polyoxyethylene styrylphenyl ether, polyoxyethylene alkyl
`esters, alkyl aryl sulfates, and the 1出e. The surfactants may
`be used singly or in a suitable combination. Surfactants
`which can uniformly mix with the desired pesticide or the
`pesticides and water are preferred but it is not always
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`necessary to use such surfactants. It is sufficient that surfac(cid:173)
`tants be dissolved in water when the pesticidal composition
`is diluted with water.
`
`to be controlled, the time period for treatment, the method of
`application, etc. and is not definitively given but is generally
`in a range of from 20 to 10,000 times.
`
`[0063] The term "wetting surfactant" as used herein
`includes any agent which may be employed to enhance the
`wetting properties of the formulation such as sodium N-me(cid:173)
`thyl-N-oleyl taurate, sodium N-methyl-N-palmityl taurate,
`sodium N-methyl-N-oleoyl taurate, sodium dioctyl sulfas(cid:173)
`uccinate and other sodium alkyl sulfosuccinates, sodium
`lauryl sulfate, alpha-(p-nonylphenyl)-omega-hydroxy poly(cid:173)
`(oxyethylene) with an average of 8-12 moles of ethylene
`oxide, and alpha-(p-octylphenyl)-omega-hydroxy poly(oxy(cid:173)
`ethylene) with an average of 7-12 moles of ethylene oxide
`
`[0064] The term "dispersing surfactant" as used herein
`includes any agent which may be employed to enhance the
`dispersion of the formulation when mixed in water such as
`sodium alkyl naphthalene sulfonate, sodium naphthalene
`sulfonate, calcium lignosulfonate, sodium lignosulfonate,
`and ammonium lignosulfonate.
`
`[0068] A preferred water-soluble pesticide for use in the
`formulations of the present invention is emamectin ben(cid:173)
`zoate. Certain avermectin Bla/Blb compounds which have
`activity as agricultural insecticides are disclosed in U.S. Pat.
`No. 4,310,519 (issued Jan. 12, 1982). The compound
`4"deoxy-4"-epi-methylamino avermectin hydrochloride is
`disclosed in U.S. Pat. No. 4,874,749 (issued Oct. 17, 1989)
`as having properties as an agricultural insecticide. Stable
`salts of 4"-deoxy-4"-epi-methylamino avermectin Bla/Blb
`are disclosed in U.S. Pat. No. 5,288,710 (issued Feb. 22,
`1994).
`
`In particular, U.S. Pat. No. 5,288,710 discloses the
`[0069]
`benzoate salt of 4"-deoxy-4"-epi-methylamino avermectin
`Bla/Blb (emamectin benzoate) which has the structure,
`e.g.:
`
`cfon
`
`(HorCH3)
`
`OH
`
`term "defoaming agent" as used herein
`[0065] The
`includes any agent which may be employed to reduce the
`tendency of the formulation to induce the generation of foam
`when added to water such as methylated silicones, polyor(cid:173)
`ganosiloxane, and 2-ethylhexanol
`
`In addition to the pesticide, the water-soluble filler,
`[0066]
`the wetting surfactant, the dispersing surfactant and the
`defoaming agent, the instant pesticidal compositions may
`also appropriately contain stabilizers, synergists, coloring
`agents, etc.
`
`[0067] The pesticidal compositions of the present inven(cid:173)
`tion are generally spread after diluting with water. One
`skilled in the art will appreciate that when diluted with
`water, the dilution magnification of the pesticidal composi(cid:173)
`tion varies depending upon the kind of pesticide, the kind of
`harmful organism to be controlled, the kind of crops to be
`treated, the kind of blight to be mitigated, the kind of weeds
`
`[0070] This compound may be readily prepared by the
`methodology describe therein. The other ingredients in the
`subject formulations are either commercially available, or
`are readily prepared by methods known in the art.
`
`[0071] The use of the present formulations will be readily
`apparent to one skilled in the art. In particular, formulations
`comprising emamectin benzoate may be utilized e.g. as
`described in U.S. Pat. No. 5,288,710.
`
`[0072] The pesticidal compositions of the present inven(cid:173)
`tion may be used to exterminate or control harmful organ(cid:173)
`isms or regulate plant growth.
`
`[0073] The pesticidal compositions of the present inven(cid:173)
`tion are particularly useful in combating agricultural pests
`that inflict damage upon crops while they are growing or
`while in storage. The compounds are applied using known
`
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`5
`
`Aug. 22, 2002
`
`techniques as sprays, dusts, emulsions and the 1出e, to the
`growing or stored crops to effect protection from such
`agricultural pests.
`
`with suspending agent such as bentonite and a wetting agent
`or like excipient. Generally, the drenches also contain an
`antifoaming agent.
`
`[0074] For example, the compound emamectin and the
`agriculturally acceptable salts thereof, in particular, ema(cid:173)
`mectin benzoate exhibit significant parasiticidal activity as
`anthelmintics, ectoparasiticides, insecticides and acaricides,
`in human and animal health and in agriculture.
`
`[0075] Emamectin and the agriculturally acceptable salts
`thereof are useful against insect pests of stored grains such
`as Tribolium sp., Tenebrio sp., and of agricultural plants
`such as spider mites, (Tetranychus sp.), aphids, (Acyrthio(cid:173)
`siphon sp.); against migratory orthopterans such as locusts
`and immature stages of insects living on plant tissue. These
`pesticides are useful as a nematocide for the control of soil
`nematodes and plant parasites such as Meloidogyne sp
`which may be of importance in agriculture. These pesticides
`are also active against other plant pests such as the southern
`army worm and Mexican bean beetle larvae. These pesti(cid:173)
`cides also have activity against Dirofilaria in dogs; N ama(cid:173)
`tosp订oides, Syphacia, Aspiculuris in rodents; the arthropod
`ectoparasites of animals and birds such as ticks, mites, lice,
`fleas, and blowfly; in sheep Luc山a sp.; biting insects and
`such migrating diperous larvae as Hypoderma sp. in cattle;
`Gastrophilus in horses; and Caterebra sp. in rodents. In
`addition these compounds are also active against parasitic
`worms known as helminths. Helminthiasis is a prevalent and
`serious economic problem in domesticated animals such as
`swine, sheep, horses, cattle, goats, dogs, cats and poultry
`Among the helminths, the group of worms described as
`nematodes causes widespread and often times serious infec(cid:173)
`tion in various species of animals. The most common genera
`of nematodes infecting the animals referred to above are
`Haemonchus, Trichostrongylus, Ostertag团， Nematodirus,
`Cooperia, Ascaris, Bunostomum, Oesophagostomum, Chab(cid:173)
`ertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Cap(cid:173)
`illaria, Hetera伈s, Toxocara, Ascaridis, Oxyuris, Ancylos(cid:173)
`toma, Uncinaria, Toxascaris and Parascaris. Certain of these,
`such as Nematodirus, Cooperia and Oesphagostomum attack
`primarily the intestinal tract while others, such as Haemon(cid:173)
`chus and Ostertagia, are more prevalent in the stomach while
`still others such as Dictyocaulus are found in the lungs.
`These pesticides are also useful against parasites which
`infect humans. The most common genera of parasites of the
`gastro-intestinal tract of man are Ancylostoma, Necator,
`Ascaris, Strongyloides, Trichinella, Capillaria, Trichuris,
`and Enterobius. Other medically important genera of para(cid:173)
`sites which are found in the blood or other tissues and organs
`outside the gastrointestinal tract are the filiarial worms such
`as Wuchereria, Brug团， Onchocerca and Loa, Dracunculus
`and extra intestinal stages of the intestinal worms Strongy(cid:173)
`loides and Trichinella. The compounds are also of value
`against arthropods parasitizing man, b山ng insects and, other
`dipterous pests causing annoyance to man. These pesticides
`are also active against household pests such as the cock(cid:173)
`roach, Blatella sp., clothes moth, Tineola sp., Carpet beetle,
`Attagenus sp., and the housefly Musca domestica.
`
`If desired, the pesticidal compositions of the
`[0076]
`present invention may be employed to formulate a _liquid
`drench. The drench is normally a solution, suspens10n or
`dispersion of the active ingredient usually in water together
`
`[0077] The optimum amount of pesticide to be employed
`for best results will, of course, depend upon the particular
`pesticide employed, the species of animal or plant to be
`treated and the type and severity of parasitic infection or
`infestation. The optimum amount of pesticide
`to be
`employed is considered to be readily determined by one
`skilled in the art without undue experimentation.
`
`[0078] Methods for preparing the formulations of the
`present invention are illustrated in the following Examples.
`The following examples are given for the purpose of illus(cid:173)
`trating the present invention and shall not be construed as
`being limitations on the scope or spirit of the instant inven(cid:173)
`tion.
`
`EXAMPLE 1
`
`[0079] Representative compositions of the emulsifiable
`concentrate (EC) formulation and of the soluble granule
`(SG) formulation are given below:
`
`Emulsifiable Concentrate Formulation of Emamectin Benzoate
`
`Ingredient
`
`Trade name
`
`%w/w
`
`Emamectin Benzoate
`Butylated hydroxytoluene
`Paraffinic oil
`POE 30 castor oil
`Polysorbate 80
`1-hexanol
`
`(Techmcal AI)
`BHr
`Semtol 70
`Witconol 300
`Tween 80
`Epal 6
`
`240
`1 00
`6 40
`18 00
`18 00
`5420
`
`[0080] The emulsifiable composition was made by blend(cid:173)
`ing all ingredients together and stirring until dissolved
`
`Soluble Granule Formulation of Emamectin Benzoate
`
`Ingredient
`
`Trade name
`
`%w/w
`
`(Techmcal AI)
`Emamectin Benzoate
`Rhodorsil EP 6703
`Polyorganosiloxane
`Sodium alkyl naphthalene sulfonates Sellogen DFL
`Adinol OT-64
`Sodium N-methyl N-oleyl taurate
`Anhydrous lactose
`Duect Tableting Grade
`
`Ingredient
`
`Trade name
`
`(Techmcal AI)
`Emamectin Benzoate
`Rhodorsil EP 6703
`Polyorganosiloxane
`Sodium alkyl naphthalene sulfonates Sellogen DFL
`Adinol OT-64
`Sodium N-methyl N-oleyl taurate
`Anhydrous lactose
`Duect Tableting Grade
`Water
`(Techmcal)
`
`5 31
`0 10
`1 00
`7 50
`86 09
`
`kg
`
`1 078
`0 020
`0 200
`1 500
`17 207
`2 795
`
`[0081] The soluble granule formulation was prepared as
`follows on a pilot scale in 5x20 kg lots to give 100 kg of
`formulation. The first step in the process was the dry
`blending of the active ingredient emamectin benzoate with
`the excipients followed by the add山on of approximately
`14% by weight of water in a 60 liter portable blender. The
`wet mass was then transfered to a basket extruder filled with
`a 0.8 mm screen. The extrudate was dried on a fluidized bed
`
`6
`
`

`

`US 2002/0114821 Al
`
`6
`
`Aug. 22, 2002
`
`dryer for approximately 12 minutes at about 60°C. The
`granules were transfered to sieving equipment where par(cid:173)
`tides outside the specified range of 4 to 50 mesh were
`segregated. The overall campaign yield was 91 % with yield
`losses due to segregation of product falling outside the
`particle size specification. The final product meeting the
`particle size was bulk packaged in 10 kg bags
`
`Soluble Granule Formulation of Emamectm Benzoate
`
`Ingredient
`
`Trade name
`
`Emamectin Benzoate
`Polyorganosiloxane
`
`(Techmcal AI)
`Antifoam/
`Rhodorsil EP-6703
`Sodium alkyl naphthalene sulfonates Sellogen DFL
`Adinol OT-64
`Sodium N-methyl N-oleyl taurate
`Lactose DCL 21
`Lactose
`
`Ingredient
`
`Trade name
`
`Emamectin Benzoate
`Polyorganosiloxane
`
`(Techmcal AI)
`Antifoam/
`Rhodorsil EP-6703
`Sodium alkyl naphthalene sulfonates Sellogen DFL
`Adinol OT-64
`Sodium N-methyl N-oleyl taurate
`Lactose DCL 21
`Lactose
`Water
`(Techmcal)
`
`%w/w
`
`5 20
`010
`
`1 00
`7 50
`86 2
`
`kg
`
`512
`0 098
`
`0 984
`7 38
`8488
`10 0
`
`[0082] The soluble granule form