(12) United States Patent
`Misselbrook et al.
`
`I 1111111111111111 11111 lllll 111111111111111 11111 lllll 111111111111111 11111111
`US006387388Bl
`US 6,387,388 Bl
`May 14, 2002
`
`(10) Patent No.:
`(45) Date of Patent:
`
`(54) PESTICIDAL FORMULATION
`
`(75)
`
`Inventors: John Misselbrook, Southampton (GB);
`Robert F. Peterson, Jr., Abington, PA
`(US)
`
`(73) Assignee: Merck & Co., Inc., Rahway, NJ (US)
`
`(*) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by O days.
`
`(21) Appl. No.: 09/318,111
`
`(22) Filed:
`
`May 25, 1999
`
`(Under 37 CFR 1.47)
`
`Related U.S. Application Data
`
`(63) Continuation of application No. 09/146,463, filed on Sep. 3,
`1998, now abandoned, 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.
`
`Int. CI.7 ................................................ AOlN 25/12
`(51)
`(52) U.S. Cl. . …….. ………….. 424/409; 424/405; 424/406;
`424/417; 514/30
`(58) Field of Search .. …….. …………... 424/405, 408-409,
`424/717-421; 514/30, 29, 28
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`3,090,723 A
`4,411,694 A
`4,439,488 A *
`4,834,977 A
`5,288,710 A
`5,656,615 A *
`5,714,157 A
`
`5/1963 Pastac
`10/1983 Smith et al.
`3/1984 Trimnell et al. ……. 428/402.24
`5/1989 Kohama et al.
`2/1994 Cvetovich
`8/1997 Camden ...................... 514/76
`2/1998 Sandell et al.
`
`FOREIGN PATENT DOCUMENTS
`
`DE
`EP
`
`4 336 307
`0 112 438
`
`4/1995
`4/1984
`
`GB
`GB
`JP
`JP
`WO
`WO
`WO
`
`2221621
`2 238 960
`5 6081 510
`6 092 803
`WO 90/12503
`WO 95/00153
`WO 95/20877
`
`* 2/1990
`6/1991
`7 /1981
`4/1994
`11/1990
`1/1995
`8/1995
`
`OTHER PUBLICATIONS
`
`Banaker, "Role of Ingredients and Exceipients in Develop(cid:173)
`ing Pharmaceuticals", Manufacturing Chemist, p. 32 (Apr
`1994).
`J.L. Hudson and O.R. Tarwater, "Reduction of Pesticide
`Toxicity by Choices of Formulation" ACS Symposium
`series#371. Pesticide Formulations, Ch. 11, pp. 124-130
`(1988).
`Lerk, C.F., "Consolidation and Compaction of Lactose",
`Drug Development and Industrial Pharmacy, 19, 2359
`(1993).
`Derwent WPI Database, Abstract 94--147816, "Water
`Soluble agricultural chemical granules----comprise water
`soluble agricultural chemical active component", Japan
`Patent Pub. JP 6092 803 (Apr. 5, 1994).
`Food and Agriculture Organization of the United Nations,
`"Manual of the Development and Use of FAQ Specification
`for Plant Protection Products", FAO Plant Production and
`Protection Paper#85, Appendix C, pp. 96-104 1985
`* cited by examiner
`
`Primary Examiner-Neil S. Levy
`(74) Attorney,Agent, or Firm—J. Eric Thies; David L. Rose
`ABSTRACT
`(57)
`
`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
`
`11 Claims, No Drawings
`
`1
`
`TIDE 1005
`
`

`

`1
`
`US 6,387,388 Bl
`
`2
`
`PESTICIDAL FORMULATION
`
`CROSS REFERENCE TO RELATED
`APPLICATIONS
`
`This application is a continuation of U.S. Ser. No. 09/146,
`463, filed Sep. 3, 1998,ABD, which is a continuation of U.S.
`Ser. No. 08/744,809, filed Nov. 6, 1996, ABD, which claims
`priority under 35 U.S.C. §119(e) from U.S. Ser. No.
`60/006,346, filed Nov. 8, 1995.
`
`FIELD OF THE INVENTION
`
`table powders (WP), water dispersible granules (WDG) or
`dry 且owables (DF), but they do not even mention soluble
`granule (SG) formulations.
`The soluble granule (SG) formulation of the present
`5 invention has numerous advantages over the corresponding
`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 dis(cid:173)
`solved in water the SG formulation provides a clear solution
`10 which is aesthetically pleasing. The SG formulation also
`minimizes the use of ingredients of environmental concern
`by eliminating the need for volatile organic compounds and
`The p resent mvent10n relates to pesticidal compos1t10ns
`employing fillers which are biologically derived, thereby
`diminishing the potential environmental impact. In add山on,
`comprising a water-soluble pesticide and process for their
`manufacture. More specifically, the invention relates to 15 formulations of higher concentration (hence lower cost per
`kg of active mgredient formulated can be achieved without
`soluble granule (SG) formulations comprising a water-
`)
`soluble pesticide and a water-soluble filler.
`any loss in biological activity with respect to a liquid
`formulation. Because the dried granules in the SG formu(cid:173)
`BACKGROUND OF THE INVENTION
`lation are of roughly constant bulk density, the granules may
`Emulsifiable concentrate (EC) agricultural formulations 20 be measured by volume, thus making them equally conve-
`of pesticides are well known in the art. These formulations
`nient to liquid formulations in ease of use
`generally comprise emulsifying and dispersing agents in
`More importantly, however, use of the instant SG formu-
`add山on to the pesticide to give a uniform solution.
`lation is less risky to personnel than the corresponding liquid
`formulation. Risk of exposure is generally evaluated under
`However, these agricultural formulations suffer numerous
`drawbacks because they are liquid. In particular, liquid
`the guide: risk=hazardxexposure. Because the instant SG
`pesticidal formulations must be handled carefully to mini-
`formulation is less toxic, the hazard is decreased. In
`add山on, the probab山ty of contact is lower when the mate-
`mize safety concerns, particularly dermal and ocular irrita-
`rial is in a solid rather than a liquid form and hence the
`tion.
`degree of exposure is also reduced. The present invention
`Although solvent-free pesticidal compositions are known,
`most solvent-free pesticidal formulations have lower bioac- 30 also affords relatively hard non-dusty granules, thereby even
`further diminishing the risk of exposure to dust from the
`tivity than the corresponding emulsifiable concentrate for-
`mulations. Thus, one s伈lled in the art frequently has been
`composition. Also, the present invention may be practiced
`forced to choose between using a solvent to give a more
`without the use of mineral fillers which contain crystalline
`bioactive formulation but with higher dermal and ocular
`silica, a known carcinogen. Thus, the present invention
`toxicity, or having a less active solid formulation
`山m1mshes the risk of exposure and provides greater handler
`safety, especially with regard to ocular irritation, than a
`The present invention overcomes the drawbacks of liquid
`liquid formulation.
`formulations by taking advantage where possible of the
`water solub山ty of the pesticide to furnish a composition in
`Accordingly, the present invention provides a relatively
`divided form so that it will dissolve in water.
`safe, bionatural delivery system for a pesticide which is
`40 water soluble at the concentration at which it is employed.
`Certain methods for preparing water-soluble granules of
`pesticides are known in the art. PCT Publication No. WO
`90/12503 discloses the formation of alkaline salts of soluble
`· ·T h e present invention relates to a pesticidal composition
`acidic or phenolic pesticides to give a granular compos1t10n
`U.S. Pat. No. 4,511,395 discloses wettable herbicidal pow- 45 of a water-soluble pesticide and processes for its manufac(cid:173)
`ture. More specifically, the invention relates to a soluble
`der compositions which comprise a swelling hydrous silicate
`clay. EPO Publication No. EP 0,111,112 discloses pesticide
`granule (SG) pesticidal formulation comprising a water-
`soluble pesticide and a water-soluble filler. The present
`granules comprising an inert carrier and a pesticide, and
`which are coated with finely divided silica.
`invention provides a pesticidal formulation with efficacy
`The use of lactose as a solid filler to make tablets is well so equal to the corresponding liquid formulation, yet with
`improved handler safety, such as lower eye irritation
`known in the pharmaceutical industry. (See e.g. Lerk, C. F.,
`"Consolidation and Compaction of Lactose" Drug Devel-
`opment and Industrial Pharmacy, 19, 2359 (1993); "Role of
`Ingredients and Excipients in Developing Pharmaceuticals"
`The present invention is directed to an pesticidal compo-
`Manufacturing Chemist, p. 32 (April 1994). Nevertheless, 55
`s1t10n comprising a water-soluble pesticide and processes for
`the use of lactose or other water-soluble fillers as agricultural
`its manufacture. More specifically, the invention relates to a
`inert ingredients is not common in formulating pesticides for
`soluble granule (SG) formulation comprising a water-
`crop protection. Hudson and Tarwater (Reduction of Pesti-
`soluble pesticide, such as emamectin benzoate, and a water-
`cide Toxicity by Choices of Formulation, J. L. Hudson and
`0. R. Tarwater, in ACS Symposium series #371, Pesticide 60 soluble filler, such as lactose.
`The pesticidal composition of the present invention com-
`Formulations, B. Cross and H. B. Scher, eds.) discuss the
`effect the choice of formulation on toxicity, and state (on p.
`prises: a water-soluble pesticide; and a water-soluble filler.
`129) that the ocular irritation can be very different for
`The present pesticidal composition may further comprise
`different formulations of the same active ingredient, and that
`a wetting surfactant; and/or a dispersing surfactant.
`changes in the other toxicity categories may occur. 65 Optionally, a defoaming agent may also be present
`Nevertheless, they do not discuss how such diminished
`Preferably the water-soluble pesticide is selected from
`toxicity may be achieved. Furthermore, they mention wet-
`emamectin or an agriculturally acceptable salt thereof. Pref-
`
`25
`
`35
`
`SUMMARY OF IBE INVENTION
`
`DETAILED DESCRIPTION OF THE
`INVENTION
`
`2
`
`

`

`3
`
`US 6,387,388 Bl
`
`4
`
`More preferred pesticidal compositions of the present
`erably the water-soluble filler is selected from: lactose,
`sucrose, glucose, and the 1如e. Preferably the wetting sur-
`invention comprise 1 to 50% by weight of emamectin
`benzoate; 40 to 99% by weight of lactose; O to 10% by
`factant is selected from: sodium N-methyl-N-oleyl taurate,
`weight of sodium N-methyl N-oleyl taurate; 0 to 2% by
`sodium N-methyl-N-palmityl taurate, sodium N-methyl-N-
`oleoyl taurate, sodium dioctyl sulfosuccinate and other s weight of sodium alkyl naphthalene sulfonate; and O to 1 %
`sodium alkyl sulfosuccinates, sodium lauryl sulfate, alpha-
`(
`by weight of polyorganosiloxane not to the exclusion of
`(p-nonylphenyl)-omega-hydroxy poly(oxyethylene) with an
`other ingredients). Even more preferred pesticidal compo(cid:173)
`average of 8-12 moles of ethylene oxide, and alpha-(p-
`sitions are those which may comprise 1 to 20% by weight of
`octylphenyl)-omega-hydroxy poly(oxyethylene) with an
`emamectin benzoate.
`average of 7-12 moles of ethylene oxide. Preferably the
`Even more preferred pesticidal compos山ons of the
`dispersing surfactant is selected from: sodium alkyl naph- 10
`present invention comprise 1 to 20% by weight of emamec-
`thalene sulfonate, sodium napthalene sulfonate, calcium
`tin benzoate; 60 to 99% by weight of lactose; 5 to 10% by
`lignosulfonate, sodium lignosulfonate, and ammonium
`weight of sodium N-methyl N-oleyl taurate; 0.5 to 2% by
`lignosulfonate. Preferably the defoaming agent is selected
`from: methylated s山cones, polyorganosiloxane, and
`weight of sodium alkyl naphthalene sulfonate; and Oto 0.5%
`2-ethylhexanol.
`15 by weight of polyorganos1loxane (not to the exclus10n of
`More preferably the water-soluble pesticide is emamectin
`other ingredients). Still more preferred pesticidal composi-
`or emamectin benzoate. More preferably the water-soluble
`tions are those which comprise 1 to 10% by weight of
`filler is lactose. More preferably the wetting surfactant is
`emamectin benzoate
`sodium N-methyl N-oleyl taurate. More preferably the dis-
`It will be appreciated by one skilled in the art that the sum
`persing surfactant is sodium alkyl naphthalene sulfonate. 20 of the proportions of emamectin benzoate, lactose, sodium
`More preferably the defoaming agent is polyorganosiloxane.
`N-methyl N-oleyl taurate, sodium alkyl naphthalene sul-
`The pesticidal composition of the present invention may
`fonate and polyorganosiloxane are not greater than 100% by
`be provided in the form of a wettable powder but preferably
`weight and that the exact concentrations of the components
`is in the form of a water-soluble granule. Similarly, the
`may vary depending on the presence of impurities
`pesticidal composition of the present invention may be
`Especially preferred pesticidal formulations are as fol-
`provided as an aggregate, a matrix, or a monolith, such as a
`lows
`brick, pellet, tablet, stick, film, sheet, and the like.
`Soluble granules comprising about 5.3% by weight of
`Preferably, the pestlc1dal compos1t10n of the present mven-
`emamectin benzoate; about 86% by weight of lactose; about
`tion is embedded in a water-soluble matrix or monolith. It
`7.5% by weight of sodium N-methyl N-oleyl taurate; about
`also will be appreciated by one skilled in the art that the 30
`1 % by weight of sodium alkyl naphthalene sulfonate; about
`present mvention further includes encasement of the instant
`0.1 % by weight of polyorganosiloxane
`pesticidal compositions in a water-soluble package, such as
`The present invention further includes a process for
`a pouch, sachet, bag, capsule, and the 1出e
`preparing a soluble granule formulation which process com-
`The pesticidal compositions of the present invention 35 pnses:
`comprise 0.1 to 90% by weight of a water-soluble pesticide,
`(1) forming a powder blend of a water-soluble pesticide
`preferably emamectin benzoate; and 30 to 99.9% by weight
`and a water-soluble filler;
`of a water-soluble filler, preferably lactose (not to the
`(2) adding water to the blend;
`exclusion of other ingredients).
`(3) extruding the wet blend through a die to form gran-
`It will be appreciated by one skilled in the art that the sum
`ules; and
`of the proportions of the water-soluble pesticide and the
`(4) drying the granules to remove the water.
`water-soluble filler are not greater than 100% by weight and
`The present invention is further directed to a soluble
`that the exact concentrations of the components may vary
`granule formulation prepared by such process
`depending on the presence of impurities
`In a preferred embodiment, the process for preparing a
`In a more preferred embodiment, the pesticidal compo-
`45 soluble granule formulation comprises:
`sitions of the present invention comprise 0.1 to 60% by
`(1) forming a powder blend of a water-soluble pesticide,
`weight of a water-soluble pesticide, preferably emamectm
`a water-soluble filler, a wetting surfactant and a dis-
`benzoate; 40 to 99.9% by weight of a water-soluble filler; 0
`persing surfactant;
`to 50% by weight of a wetting surfactant; 0 to 50% by
`(2) adding water to the blend;
`weight of a dispersing surfactant; 0 to 5% by weight of a 50
`defoaming agent (not to the exclusion of other ingredients).
`(3) extruding the wet blend through a die to form gran-
`ules; and
`It will be appreciated by one skilled in the art that the sum
`of the proportions of the water-soluble pesticide, the water-
`(4) drying the granules to remove the water.
`soluble filler, the wetting surfactant, the dispersing surfac-
`Optionally, in this process a defoaming agent may be
`tant and the defoaming agent are not greater than 100% by 55 added to the powder blend
`weight and the exact concentrations of the components may
`The present invention is further directed to a soluble
`vary depending on the presence of impurities.
`granule formulat10n prepared by such process
`In one embodiment of the present invention the formu-
`Specifically exemplifying the present invention is the
`lation contains about 0.1 to 90% by weight of the water-
`process comprising the steps of:
`(1) formmg a powder blend of a emamectin benzoate and
`soluble pesticide.
`lactose;
`Preferred pesticidal compositions of the present invention
`comprise 0.1 to 60% by weight of emamectin benzoate; 40
`(2) adding water to the blend;
`to 99.9% by weight oflactose; 0 to 25% by weight of sodium
`(3) extruding the wet blend through a die to form gran-
`N-methyl N-oleyl taurate; 0 to 10% by weight of sodium
`ules; and
`alkyl naphthalene sulfonate; and O to 3% by weight of 65
`(4) drying the granules to remove the water.
`polyorganosiloxane (not to the exclusion of other
`A preferred embodiment which specifically exemplifies
`the present invention is the process comprising the steps of
`ingredients).
`
`60
`
`25
`
`40
`
`3
`
`

`

`5
`
`US 6,387,388 Bl
`
`6
`
`The term "water-soluble filler" as used herein includes
`(1) forming a powder blend of a emamectin benzoate,
`any water soluble or water dispersible agent which may be
`lactose, sodium alkyl naphthalene sulfonate, sodium
`employed to dilute the pesticide. Preferred water-soluble
`N-methyl N-oleyl taurate, and polyorganosiloxane;
`agents include those which are biologically derived. Appro-
`(2) adding water to the blend;
`s priate water-soluble fillers include lactose, glucose, fructose,
`(3) extruding the wet blend through a die to form gran-
`ules; and
`mannose, manmtol, sucrose, such as confect10ner's sugar,
`(4) drying the granules to remove the water.
`black sugar, brown sugar, soft brown sugar, other sugars or
`saccharides, microcrys~alline cellulose, powdered cellulose,
`The present invention is further directed to a soluble
`calcium phosphate(s), morganic water-soluble salts, and the
`granule formulation of emamectin benzoate prepared by
`10 like, and mixtures thereof. Examples of lactose which can be
`such process.
`used in the present invention include hydrated a-lactose,
`The present invention is further directed to a delivery
`anhydrous a-lactose, hydrated~-lactose, anhydrous
`system for water-soluble pesticides, in particular, emamectin
`benzoate, which comprises soluble granules and the use
`~-lactose, and the like, and mixtures thereof.
`thereof.
`Any surfactants can be used as the surfactant in the
`.
`The present invention further provides a method for
`15 present mvention, as long as it will emulsify the desired
`administering the water-soluble pesticide comprising
`pesticide, or the pesticide when mixed with water. Examples
`.
`(1) formulating the water-soluble pesticide as a soluble
`of such surfactants mclude glycerine fatty acid esters,
`granule;
`sucrose fatty acid esters, sorbitan fatty acid esters, fatty acid
`()
`2 mixing with water a portion of the soluble granule
`salts, alkyl sulfates, alkylbenzene sulfonic acid salts, alkyl
`sufficient to give the desired amount of active mgred1-
`20 aryl ethers and polyoxyethylenated products thereof, ethyl-
`ent of the water-soluble pesticide; and
`ene oxide add山on products of higher alcohols, polyoxyeth-
`(3) applying the pesticide/water mixture.
`ylene polyoxypropylene glycol, lignin sulfonic acid salt,
`The present invention is further directed to a pesticide/
`polyoxyethylene styrylphenyl ether, polyoxyethylene alkyl
`water mixture prepared by such process.
`esters, alkyl aryl sulfates, and the 1出e. The surfactants may
`The application of the pesticide/water mixture may be
`conducted by methods well known in the art, including, 25 be used singly or in a suitable combination. Surfactants
`spraying, misting, dripping, infusing, injecting, irrigatmg, ·w h i c h can uniformly mix with the desired pesticide or the
`and the like.
`pesticides and water are preferred but it is not always
`necessary to use such surfactants. It is sufficient that surfac-
`The term "water-soluble pesticide" as used herein
`includes any biologically active pesticidal agent or crop
`tants be dissolved in water when the pesticidal composition
`protection chemical which is water soluble at the concen- 30 is diluted with water.
`The term "wetting surfactant" as used herein includes any
`tration in which it is employed (i.e. the agent is water soluble
`at the volume used in field application). Such water-soluble
`agent which may be employed to enhance the wetting
`properties of the formulation such as sodium N-methyl-N-
`pesticides include certain fungicides, herbicides, such as
`plant growth regulators, and insecticides, such as
`oleyl taurate, sodium N-methyl-N-palmityl taurate, sodium
`nematocides, anti-helmentics, and miticides. Exemplary 35 N-methyl-N-oleoyl taurate, sodium dioctyl sulfosuccinate
`water-soluble pesticides which may be employed in the
`and other sodium alkyl sulfosuccinates, sodium lauryl
`sulfate, alpha-(p-nonylphenyl)-omega-hydroxy poly
`present invention include: the fungicides: blasticidin-S,
`kasugamycin, and hymexanol; the herbicides: acifluorfen,
`(oxyethylene) with an average of 8-12 moles of ethylene
`oxide, and alpha-(p-octylphenyl)-omega-hydroxy poly
`glyphosate, and glufosinate; the plant growth regulants:
`gibberellic acid, maleic hydrazide and dikegulac; and the 40 (oxyethylene) with an average of 7-12 moles of ethylene
`insecticides: acephate, emamectin, and emamectin benzoate.
`oxide.
`A particularly preferred water-soluble pesticide is
`The term "dispersing surfactant" as used herein includes
`emamectin, or an agriculturally acceptable salt thereof, such
`any agent which may be employed to enhance the dispersion
`as the salt formed with benzoic acid, salicyclic acid, gallic
`of the formulation when mixed in water such as sodium
`如d, benzenesulfonic acid, hydrochloric and citric acid, 45 alkyl naphthalene sulfonate, sodium naphthalene sulfonate,
`calcium lignosulfonate, sodium lignosulfonate, and ammo-
`especially emamectin benzoate. One skilled in the art will
`readily appreciate that these pesticides exh伽t sufficient
`nium lignosulfonate
`water solubility that they will dissolve when mixed with
`The term "defoaming agent" as used herein includes any
`water at the labeled use rate. For example, commercial label
`agent which may be employed to reduce the tendency of the
`use rates of acephate are as high as 1.33 lb (0.60 kg) in a so formulation to induce the generation of foam when added to
`water such as methylated silicones, polyorganosiloxane, and
`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
`2-ethylhexanol
`In addition to the pesticide, the water-soluble filler, the
`soluble in water at its maximum label use rate. Similarly,
`emamectin benzoate is soluble at about 10? ppm in water.
`wetting surfactant, the dispersing surfactant and the defoam-
`Thus, at a typical use rate 3.4 g of emamectm benzoate will 55 ing agent, the instant pesticidal compositions may also
`· b T
`be soluble in about 34 liters of water.
`appropriately contam sta 11zers, synergists, colonng agents,
`The term "water-soluble granule" as used herein is
`etc.
`intended to include a~y g~anular or pelletized compositions
`The pesticidal compositions of the present invention are
`which permit the active mgredient to be in solution after
`generally spread after diluting with water. One skilled in the
`dissolving in water. It is not necessary for all of the ingre- 60 art will appreciate that when diluted with water, the dilution
`magnification of the pesticidal composition varies depend-
`dients of the water-soluble granule to be in solution as long
`as the active ingredient itself is in solution. Thus, the present
`ing upon the kind of pesticide, the kind of harmful organism
`to be controlled, the kind of crops to be treated, the 灿nd of
`invention includes within its scope water-soluble granules in
`which some of the ingredients may be relatively insoluble.
`blight to be mitigated, the kind of weeds to be controlled, the
`The actual physical form of the instant pesticidal composi- 65 time period for treatment, the method of a~plication, etc. and
`is not definitively given but is generally m a range of from
`tion is not critical to the proper function of the present
`invention.
`20 to 10,000 times.
`
`4
`
`

`

`US 6,387,388 Bl
`
`7
`A preferred water-soluble pesticide for use in the formu(cid:173)
`lations of the present invention is emamectin benzoate.
`Certain avermectin Bla/Blb compounds which have activ(cid:173)
`ity as agricultural insecticides are disclosed in U.S. Pat. No.
`4,310,519 (issued Jan. 12, 1982). The compound 4"deoxy4"-
`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 dis(cid:173)
`closed in U.S. Pat. No. 5,288,710 (issued Feb. 22, 1994).
`In particular, U.S. Pat. No. 5,288,710 discloses the ben(cid:173)
`zoate salt of 4"-deoxy-4"-epi-methylamino avermectin Ela/
`Blb (emamectin benzoate) which has the structure, e.g
`
`s
`
`8
`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;
`Namatosp订oides, Syphacia, Aspiculuris in rodents; the
`arthropod ectoparasites of animals and birds such as ticks,
`mites, lice, fleas, and blowfly; in sheep Lucilia sp.; biting
`insects and such migrating diperous larvae as Hypoderma
`10 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
`
`CH/CH
`OCH/
`
`H
`
`,
`H'L
`" 儿。
`
`(HorCH3)
`
`c f o n
`
`OH
`
`animals such as swine, sheep, horses, cattle, goats, dogs, cats
`This compound may be readily prepared by the method-
`ology describe therein. The other ingredients in the subject 40 and poultry. Among the helminths, the group of worms
`described as nematodes causes widespread and often times
`formulations are either commercially available, or are
`readily prepared by methods known in the art.
`senous mfect10n m vanous species of ammals. The most
`The use of the present formulations will be readily
`common genera of nematodes infecting the animals referred
`apparent to one skilled in the art. In particular, formulations
`to above are Haemonchus, Trichostrongylus, Ostertag团，
`comprising emamectin benzoate may be utilized e.g. as 45 Nematodirus, Cooperia, Ascaris, Bunostomum,
`described in U.S. Pat. No. 5,288,710.
`Oesophagostomum, Chabertia, Trichuris, Strongylus,
`The pesticidal compositions of the present invention may
`Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara,
`be used to exterminate or control harmful organisms or
`Ascaridis, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and
`regulate plant growth
`Parascans. Certam of these, such as Nematodirus, Cooperia
`The pesticidal compositions of the present invention are
`and Oesphagostomum attack primarily the intestinal tract
`particularly useful in combating agricultural pests that inflict
`while others, such as Haemonchus and Ostertagia, are more
`damage upon crops while they are growing or while in
`prevalent in the stomach while still others such as Dictyo-
`storage. The compounds are applied using known tech-
`caulus are found in the lungs. These pesticides are also
`niques as sprays, dusts, emulsions and the like, to the
`useful against parasites which infect humans. The most
`growing or stored crops to effect protection from such
`common genera of parasites of the gastro-intestinal tract of
`agncultural pests.
`55 man are Ancylostoma, Necator, Ascaris, Strongyloides,
`For example, the compound emamectin and the agricul-
`Trichinella, Capillaria, Trichuris, and Enterobius. Other
`turally acceptable salts thereof, in particular, emamectin
`medically important genera of parasites which are found in
`benzoate exhibit significant parasiticidal activity as
`the blood or other tissues and organs outside the gastrointes-
`anthelmintics, ectoparasiticides, insecticides and acaricides,
`tinal tract are the filiarial worms such as Wuchereria, Brug团，
`60 Onchocerca and
`oa, Dracuncu us and extra mtestinal
`m human and ammal health and in agriculture.
`L
`stages of the intestinal worms Strongyloides and Trichinella
`Emamectin and the agriculturally acceptable salts thereof
`are useful against insect pests of stored grains such as
`The compounds are also of value against arthropods para-
`Tribolium sp., Tenebrio sp., and of agricultural plants such
`sitizing man, b山ng insects and, other dipterous pests caus-
`as spider mites, (Tetranychus sp.), aphids, (Acyrthiosiphon
`ing annoyance to man. These pesticides are also active
`~p.); against migratory orthopterans such as locusts and 65 against household pests such as the cockroach, Blatella sp.,
`immature stages of insects living on plant tissue. These
`clothes moth, Tineola sp., Carpet beetle, Attagenus sp., and
`pesticides are useful as a nematocide for the control of soil
`the housefly Musca domestica.
`
`50
`
`5
`
`

`

`9
`
`US 6,387,388 Bl
`
`10
`transfered to sieving equipment where particles outside the
`specified range of 4 to 50 mesh were segregated. The overall
`campaign yield was 91 % with yield losses due to segrega(cid:173)
`tion of product falling outside the particle size specification
`The final product meeting the particle size was bulk pack(cid:173)
`aged in 10 kg bags
`
`Soluble Granule Formulation of Emamectin Benzoate
`
`If desired, the pesticidal compositions of the present
`invention may be employed to formulate a liquid drench.
`The drench is normally a solution, suspension or dispersion
`of the active ingredient usually in water together with
`suspending agent such as bentonite and a wetting agent or s
`like excipient. Generally, the drenches also contain an
`antifoaming agent.
`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 10
`typ~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
`Emamectin Benzoate
`undue expenmentat10n.
`Methods for preparing the formulations of the present 15 Polyorganosiloxane
`invention are illustrated in the following Examples. The
`following examples are given for the purpose of illustrating
`the present mvention and shall not be construed as bemg
`limitations on the scope or spirit of the instant invent10n.
`
`Ingredient
`
`Sodium alkyl naphthalene sulfonates
`Sodium N-methyl N-oleyl taurate
`Lactose
`
`EXAMPLE 1
`
`Representative compositions of the emulsifiable concen(cid:173)
`trate (EC) formulation and of the soluble granule (SG)
`formulation are given below:
`
`20
`
`Emamectin Benzoate
`Polyorganosiloxane
`
`Sodium alkyl naphthalene sulfonates
`Sodium N-methyl N-oleyl taurate
`Lactose
`25 Water
`
`Trade name
`
`(Techmcal AI)
`Antifoam/
`Rhodorsil EP-6703
`Sellogen DFL
`Adinol OT-64
`Lactose DCL 21
`
`(Techmcal AI)
`Antifoam/
`Rhodorsil EP-6703
`Sellogen DFL
`Adinol OT-64
`Lactose DCL 21
`(Techmcal)
`
`%w/w
`
`5 20
`0 10
`
`1 00
`7 50
`86 2
`坚
`
`512
`0 098
`
`0 984
`7 38
`84 88
`10 0
`
`Emulsifiable Concentrate Formulation of Emamectin Benzoate
`
`Ingredient
`
`Trade name
`
`%w/w
`
`Emamectin Benzoate
`Butylated hydroxytoluene
`Paraffinic oil
`POE 30 castor 011
`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
`
`The emulsifiable composition was made by blending all
`ingredients together and stirring until dissolved.
`
`Soluble Granule Formulation of Emamectin Benzoate
`
`Ingredient
`
`Trade name
`
`(Technical AI)
`Emamectin Benzoate
`Rhodorsil EP 6703
`Polyorganosiloxane
`Sodium alkyl naphthalene sulfonates Sellogen DFL
`Sodium N-methyl N-oleyl taurate
`Adinol OT-64
`Anhydrous lactose
`Direct Tableting Grade
`
`Emamectin Benzoate
`Polyorganosiloxane
`Sodium alkyl naphthalene sulfonates
`Sodium N-methyl N-oleyl taurate
`Anhydrous lactose
`Water
`
`(Technical AI)
`Rhodorsil EP 6703
`Sellogen DFL
`Adinol OT-64
`Direct Tableting Grade
`(Technical)
`
`%w/w
`
`5.31
`0.10
`1.00
`7.50
`86.09
`竺
`1.078
`0.020
`0.200
`1.500
`17.207
`2.795
`
`The soluble granule formula