AU2004294226A1 - Improved parasiticide composition - Google Patents
Improved parasiticide composition Download PDFInfo
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- AU2004294226A1 AU2004294226A1 AU2004294226A AU2004294226A AU2004294226A1 AU 2004294226 A1 AU2004294226 A1 AU 2004294226A1 AU 2004294226 A AU2004294226 A AU 2004294226A AU 2004294226 A AU2004294226 A AU 2004294226A AU 2004294226 A1 AU2004294226 A1 AU 2004294226A1
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Description
WO 2005/053746 PCT/AU2004/001688 1 IMPROVED PARASITICIDE COMPOSITION Technical Field This invention relates to parasiticide compositions, especially water washable liquid compositions for veterinary use. 5 Background of the Invention Insecticide and parasiticide compositions are widely used in the veterinary field to deliver active substances in liquid form to animals, particularly farm animals. The insecticide/parasiticide compositions may be given to the animal orally (by way of drench) orby application to an external part of the animal. When applied to an external 10 part of the animal the insecticidefparasiticide composition is referred to as a "pour-on composition". The desirability of pour-on compositions stems from ease of use, especially when application along with effectiveness is achieved. The essence of a pour-on composition is that it is formulated as a liquid for topical application to the skin of an animal, such as along the back of the animal. 15 Desirably, a pour-on composition spreads on the skin so as to deliver effectively the insecticide/parasiticide composition to the animal. Pour-on compositions and compositions used in drenching are applied from an applicator device such as an applicator gun. It is standard practice for farmers to clean the applicator device with water after they have finished administering or applying the 20 insecticide/parasiticide composition to the animal. It may be the case, however, that the active ingredient of the insecticide/parasiticide composition is water insoluble and in such a situation the following problem (i) and possibly (ii) occur: (i) the applicator becomes clogged due to crystallisation of the active substance from the insecticide/parasiticide composition; and 25 (ii) a change in the concentration of the active substance administered from the applicator may occur as a result of the active substance crystallising in the applicator and being included in the next dose of insecticide/ parasiticide administered to the animal. Insect growth regulators (IGR), such as triflumuron, are used to destroy insect 30 larva. Essentially, IGR's prevent the fonxuation of new chitin during the insects moulting stage. Chitin is the substance that makes up. the insects exoskeleton and IGR's act as a chitin synthesis inhibitor by preventing the enzyme necessary to produce chitin from functioning. In particular, IGR's are an external parasiticide which prevents the development of immature lice present in the fleece of sheep. 35 Accordingly, IGR'!s such as triflumuron are used as active substances in parasiticide compositions but due to the fact that they are water insoluble, the problems WO 2005/053746 PCT/AU2004/001688 2 noted above are experienced when a parasiticide composition containing IGR's are applied to an animal via an applicator device. More specifically, the applicator becomes clogged due to crystallisation of the JOIGR from the parasiticide composition The crystallisation is due to low solubility of IGR in water and limited solvation power 5 of the solvent system in the composition. It would be desirable, therefore, to provide a water washable parasiticide composition containing an IGR. However, given the insolubility of this compound in water, there is a technical difficulty to be met in providing such a composition. Parasiticide compositions containing IGR's are routinely applied to animals 10 whose hide/fur/wool is removed for human use. It is therefore necessary to ensure that the levels of IGR residing in the hide/fur/wool intended for human contact is at an acceptable level. Additionally, it is particularly desirable that the IGR loading in the waste water from textile scouring plants is also at an acceptable level. Currently the A.P.V.M.A. (Australian Pesticides and Veterinary Medicines Authority) has been 15 asked by the Australian Wool Residue Management Council to conduct a review of sheep ectoparasiticides, with particular priority given to backline products. The concern comes about from both the Australian government and wool industry with regards to public health, occupational safety, environmental and trade implications of pesticide residues on Australian wool. These concerns have driven the wool industry to 20 make efforts to reduce the levels of pesticide residues on Australian raw wool. The animals to which the parasiticide compositions containing IOR's are routinely applied, may also be reared for human consumption. It is therefore necessary to ensure that the amount of IGR residing in the consumable portions of the animal is at an acceptable level prior to consumption. The concentration of IGR in human-food 25 products derived from the animal is required to be below a Maximum Residue Limit (MRL) as set by the relevant governing authority in each country. The inventors are aware of a number of pour-on parasiticides compositions currently on the market that are only able to meet the MRL for tissues after a substantial withholding period has been observed, some being excluded from ever being used in milk producing animals, 30 Having regard to this requirement, it would therefore be desirable to provide a parasiticide composition in which the amount of IGR that can be found in human-food products derived from the animal meets the MRL in a period of time that is less than the withholding period specified for currently available parasiticide compositions Any discussion of documents, acts, materials, devices, articles or the like which 35 has been included in the present specification is solely for the purpose of providing a context for the present invention.. It is not to be taken as an admission that any or all of WO 2005/053746 PCT/AU2004/001688 3 these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application. Summary of Invention 5 In work leading up to the present invention, the inventors have identified a need for a parasiticide composition that is dispersed over the animals skin to effectively control parasites on/in an animal and results in a residual loading of the parasiticide in the hide, fur, wool and/or consumable portions of the animal that is acceptable for human contact/consumption and textile scouring effluent. 10 The present inventors have now found a means to provide an improved parasiticide composition based on an insect growth regulator (IGR), that is water washable and is effective against lice once applied to an animal and has a low level of IGR residing in the hide, fur, wool and/or consumable portions of the animal after application of the parasiticide composition to the animal. Surprisingly, this has been 15 achieved by including into the parasiticide composition specific amounts of one or more emollients together with one or more solvents. In a first aspect, the present invention is directed to a water washable parasiticide composition comprising: 0.01 - 30% w/v of one or more insect growth regulators; 20 0.01 - 20% w/v of one or more emollients; the balance being one or more organic solvents. The water washable parasiticide composition may further include one or more surfactants. Preferably, the stable insecticide/parasiticide composition includes one or more 25 synthetic pyrethroids, more preferably about 0.01-5% wiv of one or more synthetic pyrethroids (SP). In a second aspect, the present invention is directed to a method of treating parasites in/on an animal, the method comprising administering to the animal an effective amount of the parasiticide composition according to the first aspect of the 30 invention. With regard to the method of treating parasites in an animal according to the second aspect of the invention, it will be understood that an "effective amount of the parasiticide composition" means that the amount of the pasasiticide composition of the invention that is administered to the animal must be effective in treating, by way of 35 killing or repelling, the parasites on/in the animal. The present inventors have found that an "effective amount of parasiticide composition" may be achieved using a dose WO 2005/053746 PCT/AU2004/001688 4 volume that is calculated using (i) the weight of the animal or (ii) the surface area of the animal. Using (i), the preferred "effective amount of the parasiticide composition" is a dosage volume of about 10-100 mL per 50 kg of bodyweight of animal. 5 Using (ii), it has surprisingly een found that one dose volume of the parasiticide composition may be used to cover a wide range of surface areas within the target species population. Calculating a dose volume for application based on the surface area of an animal rather than its body weight has several advantages. Firstly, it allows the product to be tailored to meet its mode of administration and action. 10 Secondly, the dose regime is simplified for the applicator. Thirdly, it permits the manufacturer to select a dose volume suitable for a pour-on for a defined purpose within a simplified dosage regime. Tables 3 and 4 provide preferred dosage volumes based on (i) the weight of the animal (Table 3) and (ii) the surface area of the animal (TI'able 4) for different 15 compositions according to preferred embodiments of the first aspect of the invention. For convenience of the end user, the surface area calculations were converted back to weight range in kg. In a third aspect, the present invention is directed to the use of the parasiticide composition according to the first aspect of the invention in the preparation of a 20 medicament for the treatment of parasites in/on an animal. In a fourth aspect, the present invention is directed to a method of cleaning a device containing a water washable parasiticide composition according to the first aspect of the invention, the method comprising washing the device with au aqueous solution in a manner so as to effectively remove substantially all of the composition 25 from the device. Throughout the specification it will be understood that the term "water washable" means that when water is added to the parasiticide composition, the insect growth regulator (IGR) forms a coarse emulsion which contains fine crystals of insect growth regulator. 30 The insect growth regulator (IGR) is preferably selected from one or more of the group consisting of triflumuron, cyromazine, diflubenzron, fluazuron and methoprene and mixtures thereof.. More preferably, the IGR is triflumuron. The IGR is included in the composition in a concentration of about 0.01-30% w/v. In one embodiment, the preferred concentration of IGR is in the range of about 0.1-20%w/v, most preferably 35 about 0.1-10% w/v, even more preferably about 0.1-5% w/v. In another embodiment, WO 2005/053746 PCT/AU2004/001688 5 the preferred concentration of IGR is about 0.1-30%w/v, more preferably about 2 30%w/v. A variety of emollients may be used in the parasiticide composition of the present application. These include but are not limited to one or more of the following: 5 fatty acid esters such as cetyl acetate, cetyl palmitate, myristic acid isopropyl ester, palmitic acid isopropyl ester, steric acid isopropyl ester, cetyl lactate (e.g. Pelemol CL, Wickenol 507), acetylated lanoline (e.g. Ritacetyl), cetyl palmitate (e.g. Cutina CP), octyl stearate (e.g. Cetiol 868), isooctyl stearate, lauric acid hexyl ester (e.g. Cetiol A), butyl adipate, dibutyl adipate (e.g. Cetiol B), octyl palmitate and myrtistyl myristate 10 (e.g. Cegesoft C and Cetiol MM), myristyl lactate (e.g. Cetiol 868), glycol isostearate, caprylic acid ester and capric acid ester; a mixture of glycol distearate, laureth-4 and cocamidopropyl betaine (e.g. Euperlan PK 3000); a mixture of sodium laureth sulfate, glycol distearate and cocamide MEA (e.g. Euperlan PK 771); a mixture of glycol distearate, sodium laureth sulfate, cocamide MEA and Laureth-9 (e.g. Euperlan .PK 15 810); a mixture of triethylene glycol distearate and sodium laureth sulfate (e.g Euperlan PK 900); long chain fatty alcohols such as n-octyl dodecanol (e.g. Eutanol G), cetyl alcohol, cetyl steryl alcohol, oleyl alcohol; lanolin oil and derivatives (e.g. Lantrol HP, Ritalan); triglycerides, such as caprylic/capric triglyceride (e.g. Myritol 318) and glycol isostearate; sterols such as beta-sitosterol, campesterol, stigmasterol (e.g Avocardin); 20 distilled wool wax alcohols (e.g. Super Hartolan) and mixtures thereof. Preferably, the fatty acid esters have an alcohol component with a chain length of Cl - C2 or C4-C18 and/or an acid component with a chain length of C4 - C13 or 015 - C30. Even more preferably, the fatty acid esters have an alcohol component with a chain length of C4-C18, such as cetyl acetate, cetyl palmitate, lanoline acetate; 25 and/or an acid component with a chain length of CS - C13 or 015 - C24, such as palmitic acid isopropyl ester, storic acid isopropyl ester, lauric acid hexyl ester (e.g. Cetiol A), caprylic acid ester and capric acid ester. SPreferably, the fatty alcohols have a chain length of C8 - 018, such as cetyl alcohol, etyl steryl alcohol, oleyl alcohol, octyl dodecanol. 30 Preferably, the triglycerides have a vegetable fatty acid component with a chain length of C8-C12, such as eaprylic/capric triglyceride (e.g. Myritol 318) and glycol isostearate. Accordingly, in a preferred embodiment of the invention, the emollient is selected from one or more of the following: fatty acid esters having an alcohol 35 component with a chain length of C1 - C2 or C4-C18; fatty acid esters having an acid component with a chain length of C4 - C13 or C15 - C30; a mixture of glycol WO 2005/053746 PCT/AU2004/001688 6 distearate, laureth-4 and cocamidopropyl betaine; a mixture of sodium laureth sulfate, glycol distearate and cocamide MEA; a mixture of glycol distearate, sodium laureth sulfate, cocamide MEA and Laureth-9; a mixture of triethylene glycol distearate and sodium laureth sulfate; long chain fatty alcohols; lanolin oil; triglycerides; sterols; 5 distilled wool wax alcohols and mixtures thereof In an even more preferred embodiment, the one or more emollients is selected from fatty acid esters having an alcohol component with a chain length of C4--C18 such as cetyl acetate, cetyl palmitate, lanoline acetate; fatty acid esters having an acid component with a chain length of C8 - C13 or C15- C24 such as palmitic acid 10 isopropyl ester, steric acid isopropyl ester, laurie acid hexyl ester (e.g. Cotiol A), caprylic acid ester and capric acid ester; a mixture of glycol distearate, laureth-4 and cocamidopropyl betaine (e.g. Euperlan PK 3000); a mixture of sodium laureth sulfate, glycol distearate and coeamide MEA (e.g. Euperlan PK 771); a mixture of glycol distearate, sodium laureth'sulfate, cocamide MEA and Laureth-9 (e.g. Euperlan PK 15 810); a mixture of triethylene glycol distearate and sodium laureth sulfate (e.g Euperlan PK 900); long chain fatty alcohols of chain length CS - C18 such as cotyl alcohol, cetyl steryl alcohol, oleyl alcohol; octyl dodecanol; lanolin oil and derivatives thereof (e.g. Lantrol HP, Ritalan); triglycerides having a vegetable fatty acid component with a chain length of C8-C12 such as caprylic/capric triglyceride (e.g. Myritol 318) and 20 glycol isostoarate ; sterols such as beta-sitosterol, campesterol, stigmasterol (e.g. Avocardin); distilled wool wax alcohols (e.g. Super Hartolan) and mixtures thereof In a most preferred embodiment, the one or more emollients are selected from the group consisting of lanolin acetate, cetyl acetate, lauric acid hexyl ester; caprylic/capric triglyceride, palmitic acid isopropyl ester, cetyl alcohol and mixtures 25 thereof The one or more emollients may be combined with one or more surfactants (e.g. Solulan 98). Typically, the one or more emollients will be used in a concentration of about 0.01-20 %w/v. In one embodiment, the preferred concentration of emollient is about 0.02 - 10%w/v, more preferably about 0.05-5%w/v. In another embodiment, the 30 preferred concentration of emollient is about 0.1-20%w/v, more preferably 0.5 20%w/v. It has surprisingly been found that the addition of an emollient into the IGR containing parasiticide composition of the present invention provides both a low residue and water washable IGR composition. In a preferred embodiment of the 35 invention, in which the parasiticide composition contains triflumuron as the [GR, the inventors have found that the emollient reduces the crystal size of the triflumuron WO 2005/053746 PCT/AU2004/001688 7 during washing with water in such a way that the applicator device will not clog and can be reused again. One or more organic Solvents are included in the composition of the invention. Preferably, the one or more organic solvents are selected from the group consisting of 5 alcohols such as aliphatic and aromatic alcohols; glycols; aliphatic and/or aromatic aldehydes; ketones; aliphatic and/or aromatic hydrocarbons; polyols; glycol ethers; glycol ether acetate; C1 - C8 alkyl pyrrolidones; aliphatic and/or aromatic esters and mixtures thereof. Examples of aliphatic alcohols include but are not limited to methanol, butanol 10 and isopropyl alcohol. Examples of aromatic alcohols include but are not limited to benzyl alcohoL Examples of glycols include but are not limited to polyethylene glycols and polypropylene glycols. Examples of aliphatic hydrocarbons include but are not limited to octane. Examples of aromatic hydrocarbons include but are not limited to toluene, xylene and blends such as -Solvesso 150 and Solvesso 200. Examples of 15 ketones include but are not limited to acetone, 3-buten-2-one, butanone and oyclohexanone. Examples of glycol ethers include but are not limited to dipropyleneglycol monomethyl ether, butyl icinol and butyl di-icinol. Examples of C 1 Ca alkyl pyrrolidones include but are not limited to N-methyl pyrrolidone, 1-octyl-2 pyrrolidinone and lautyl pyrrolidone. Examples of aromatic esters include but are not 20 limited to benzyl benzoate. Examples of aliphatic esters include but are not limited to methyl acetate, ethyl acetate. Preferably, the organic solvent is selected from one or more of the group consisting of dipropyleneglycol monomethyl ether, N-methyl pyrrolidone, benzyl alcohol, toluene, xylene, benzyl benzoate, cyclohexanone, butyl di-icinol and ethyl 25 acetate and mixtures thereof. The organic solvent forms the balance of the composition. The total concentration of the solvent may be in the range of 10-99.9% w/v. Preferably, the concentration used is in the range of 20-99.5% most preferably 30-99:5% w/v. A preferred solvent is a mixture of dipropyleneglycol monomethyl ether and N-methyl 30 pyrrolidone. In a preferred embodiment of the first aspect of the invention, in which only one organic solvent is used, the solvent is benzyl alcohol, Solvesso 150 or Solvesso 200. In another preferred embodiment of the first aspect, in which both a pridiary and a secondary organic solvent are used, the primary solvent is preferably selected from N 35 methyl pyrrolidone (NMP), Solvesso 150 and Solvesso 200; and the secondary solvent WO 2005/053746 PCT/AU2004/001688 is selected from benzyl benzoate, cyclohexanone, butyl di-icinol, dipropyleneglycol monomethyl ether (DPM) and ethyl acetate. The parasiticide composition optionally includes one or more surfactants. The one or more surfactants may be selected from non-ionic, anionic, cationic or 5 amphoteric surfactants and mixtures thereof Preferably, one or more non-ionic and/or one or more anionic surfactants are used. The surfactant may also function as a spreading agent. One or more non-ionic surfactants may be selected from the group consisting of C8-C10 alkylphenol ethoxylates, such as ethoxylated nonylphenol; C9-C17 alcohol 10 ethoxylates; C8-C20 alkyl amine ethoxylates; castor oil ethoxylates; lanolin alcohol ethoxylates; sorbitan fatty acid ester ethoxylates; sorbitan fatty acid esters; allkyl aryl sulphonates and mixtures thereof The C8-C 10 alkylphenol ethoxylates preferably contain from 2 to 100 moles of ethylene oxide and may be selected from but not limited to the commercially available 15 Terio N Series products, such as those identified as Terido N9, Teric N20 and Teric N100I. The C9-C17 alcohol ethoxylates preferably contain from 2 to 25 moles of ethylene oxide and may be selected from but not limited to the commercially available products identified as Teric 9A2 and Teric 16A16. The C8-C20 alkyl amine ethoxylates preferably contain from 5 to 20 moles of ethylene oxide and may be 20 selected from but not limited to the commercially available products identified as Teric 13M15 and Teric 18M20. The castor oil ethoxylates preferably contain from 5 to 60 moles of ethylene oxide and may be selected from but not limited to the commercially available products identified as Cremophor EL, Acconon CA-5 and Teric 380. The lanolin alcohol ethoxylates preferably contain from 5 to 40 moles of ethylene oxide and 25 may be selected from but not limited to the commercially available products identified as Polycol 5 and Polycol 40. The sorbitan fatty acid ester ethoxylates preferably contain 4 to 20 moles of ethylene oxide and may be selected from but not limited to Polysorbate 20, Polysorbate 60 and Polysorbate 80. The sorbitan fatty acid esters preferably have a chain length of C18-C60 and more preferably have an HLB of 2-9 30 and may be selected from but not limited to sorbitan monoisostearate, sorbitan monostearate, Hodag SML and Span 25. Preferably, the nonionic surfactant is one or more sorbitan fatty acid ester ethoxylates (e.g. Polysorbate 80) Anionic surfactants may be selected from the group consisting of C9 - C13 35 alkyl benzene sulphonates such as sodium dodecylbenzenesulphonate and C9 - 013 alkyl sulphates such as sodium lauryl sulphate and mixtures thereof.
WO 2005/053746 PCT/AU2004/001688 9 Preferably, the surfactant is present in the parasiticide composition in a concentration of about 0.005 - 30%w/v. In one embodiment, the concentration of surfactant is preferably in the range of about 0.01 - 20% w/v, more preferably about 0.02-10% and most preferably about 0.05-5% w/v. In another embodiment, the 5 concentration of surfactant is preferably about 0.1-30%w/v, more preferably about 0.5 30%w/v. One or more synthetic pyrethroids (SP) may be used in the composition of the present invention. The synthetic pyrethroid (SP) is preferably selected from one or more of the group consisting of alphacypermethrin, cypermethrin, deltamethrin, 10 permethrin, bifenthrin and cyfluthrin and mixtures thereof. The SP may be included in the composition in a concentration of about 0.01-5.0% w/v, more preferably about 0.075-5%/ow/v. From preliminary results, the present inventors believe that the inclusion of one or more SP's in the composition of the present invention will also result in a low level 15 of SP residing in the hide, fur, wool and/or consumable portions of the animal after application of the parasiticide composition to the animal. The composition according to the invention may further include one or more fragrances. Fragrances may be in the form of essential oils including but not limited to eucalyptus oil, tea tree oil, orange oil, garlic oil and clove oil or terpenes such as d 20 limonene, a-pinene, ji-pinene, 03-myrcene and terpinolene and mixtures thereof. Preferably, fragrances are present in a range of about 1 - 5% more preferably, about 0.5 - 5% The availability of insect growth regulators, emollients, solvents, surfactants, synthetic pyrethroids and fragrances is shown in Tables 11-16, 25 The composition may further include additives which are commonly used in insecticide/parasiticide compositions including but not limited to dyes and oils such as hydrocarbon oils, mineral oils, vegetable oils and mixtures thereof The compositions of the invention may be produced by dissolving one or more IGR's in one or more organic solvents, followed by addition of the emollient and 30 optionally surfactant to the solution. The resulting solution is preferably mixed until homogenous. It will be appreciated that compositions of the invention may be produced by varying the order in which the ingredients are combined. The composition according to the first aspect of the invention may be in the form of an emulsifiable concentrate which may be further diluted with water before 35 usu. Preferably such a composition includes one or more IGR's in an amount of about 0.1-30%w/v, more preferably 2-30%w/v; one or more emollients in an amount of about WO 2005/053746 PCT/AU2004/001688 10 0.1-20%w/v, preferably about 0.5-20%w/v; the balance being one or more organic solvents. Even more preferably, the composition of the invention in the form of an emulsifiable concentrate includes one or more surfactants in an amount of about 0.1 30%w/v, preferably 0.5-30%w/v. .5 The composition according to the present invention, before or after dilution with water, may be given externally to the animal as a pour-on, spray-on or dip preparation. The composition is preferably applied externally to the skin of the animal using an applicator device, such as a gun or spray, or by submerging the animal in a bath of the dip formulation. 10 Whilst compositions made according to the invention will find the greatest application in sheep, they are also useful in treating cattle, deer, buffalo, cats, horses, dogs and goats. It will be appreciated that the parasiticide composition may be used to treat a variety of parasites which include but are not limited to lice parasites. In particular, the 15 parasiticide composition is used to treat the lice parasite in the fleece of sheep. According to one preferred embodiment of the first aspect of the invention, there is provided a water washable parasiticide composition comprising: 0.2 - 10% w/v triflumuron; 0.05 - 5% w/v one or more emollients selected from the group consisting of 20 lanolin acetate, cetyl acetate, laurie acid hexyl ester, caprylic/capric triglyceride, palmitic acid isopropyl ester, cetyl alcohol and mixtures thereof; 0.05 - 5% w/v one or more surfactants selected from the group consisting of C8 C10 alkylphenol ethoxylates, C9-CI17 alcohol ethoxylates, C8-C20 alkyl amine ethoxylates, castor oil ethoxylates, lanolin alcohol ethoxylates, sorbitan fatty acid ester 25 ethoxylates, sorbitan fatty acid esters and mixtures thereof; and 0.075- 5% w/v of one or more synthetic pyrethroids selected from the group consisting of alphacypermethrin, cypermethrin, deltamethrin, permethrin, bifenthrin and cyfluthrin and mixtures thereof-, 0.5- 5% w/v one or more fragrances selected from the group consisting of 30 eucalyptus oil, tea tree oil, orange oil, garlic oil and clove oil or terpenes such as d limonene, a-pinene, 3-pinene, j-myrcene and terpinolene and mixtures thereof; the balance being an organic solvent or a mixture of organic solvents selected from one or more of the group consisting of dipropyleneglycol monomethyl ether, N methyl pyrrolidone, benzyl alcohol, toluene, xylene, benzyl benzoate, cyclohexanone, 35 butyl di-icinol and ethyl acetate.
WO 2005/053746 PCT/AU2004/001688 11 Throughout the specification, the parasiticide composition according to the first. aspect of the invention may be referred to as a "low residue composition", a "composition that has a low residue level", a composition that results in a "low level of IGR and optionally SP residue" or a composition that will "reduce the residue loading". 5 In this context, "low residue", "low level of TOIGR and optionally SP residue" and "reduce the residue loading" is referring to the level of IGRT and optionally SP, residing in the hide, fur, wool and/or consumable portions (e.g. meat, fat and/or milk) of the animal to which the parasiticide composition has been applied. Preferably, "low residue", "low level of IGR and optionally SP residue" and "reduce the residue loading" 10 means that the level of insect growth regulator (IGR) and optionally synthetic pyrethroid (SP) present in the hide, fur, wool or consumable portions of the animal, is in a concentration that is recognised as acceptable for human contact and/or consumption within a time period that is less than the withholding period for currently available IGR containing products as specified by the relevant authorities in each 15 country, that is there is no need to treat the hide, fur, wool, and/or consumable portions to reduce the levels of IGT or SP. For instance, the inventors have surprisingly found that when triflumuron is used as the IGR in a preferred embodiment of the first aspect of the invention, the level of triflumuron is below the Maximum Residue Level set by the Australian Pesticides and Veterinary Medicines Authority of 2mg/kg in a period of 20 time that is less than the 14 day withholding period currently set for available parasiticides containing triflumuron. It will be understood that the Maximum Residue Limit (MRL) is the maximum concentration of a residue, resulting from the registered use of an agricultural or veterinary chemical, that is recommended to be legally permitted or recognised by the 25 relevant authority in a particular country, as being acceptable in or on a food, agricultural commodity or animal feed. The concentration is expressed in milligrams per kilogram of the commodity. MRL values for some IGR's published by the Australian Pesticides and Veterinary Medicines Authority are given in Table 1 below. 30 WO 2005/053746 PCT/AU2004/001688 12 Table 1: IGR Food MRL (mg/kg) Cyromazine Cattle meat 0.05 Sheep meat 0.2 Diflubenzuron Cattle meat (itt the fat) 0.02 Sheep meat (in the fat) 0.05 Methoprene Meat (mammalian, in the fat) 0.3 Triflunron Sheep meat (in the fat) 2 5 The Maximium Residue Levels for various IGR's as set by governing authorities in some other countries are given below in Table.2. 10 Table 2: MRL (mg/kg) IGR Tissue Australia NZ Codex US EPA US EU FSIS Cyromazine Cattle meat 0.05 *0,1 0.05 . 0,05 0.05 Cattle fat 0.05 0.05 Cattle meat by products 0.05 0,05 0.05 Cattle kidney 0.2 Sheep Meat 0.2 *0.1 0.05 0.05 _ 0.05 Sheep meat by products 0.05 0.05 Diflubenzuron Cattle meat (in the fat) 0.02 *0.1 Cattle meat 0.05 0.05 Cattle fat 0.05 0.05 Cattle meat by products 0.15 0.05 Sheep meat (in the fat) 0.05 *0.1 Sheep meat .. 0.05 0.05 Sheep meat by products 0.15 0.05 Sheep fat I. 0.05 WO 2005/053746 PCT/AU2004/001688 13 Methoprene Meat (mammaliam in the 0.3 *0.1 fat Cattle meat .0.1 Cattle fat .. 0.1 Cattle meat by products 0.1 Sheep meat(in the fat) 0.05 *0.1 Sheep meat 0.1 Sheep meat by products 0.1 Sheep fat 0.1 Triflumuron Sheep meat (in the fat) 2 0.05 0.05 Sheep meat 0.05 0.05 , Sheep (edible offal) * Z default MRL is 0.1 mg/kg Different withholding periods often apply to milk and meat. It will be understood that the withholding period for milk is the minimum period of time that must elapse between the last treatment of an animal with a veterinary medicine and the 5 next milking from which milk from that animal can be used for human consumption or supplied for processing. It will be understood that the withholding period for meat is the minimum period of time that must elapse between the last treatment of an animal with a veterinary medicine and its slaughter for human consumption. In Australia and most other countries throughout the world, all veterinary medicines and chemicals 10 intended for treatment of food-producing animals are required to have a withholding period stated on the label. As noted above, the Maximum Residue Limits (MRL) Standard published by the Australian Pesticides and Veterinary Medicines Authority set the MRL for triflumuron in sheep meat in the fat at 2 mg/kg (or 2 ug/g). The current triflumuron 15 containing parasiticidal products have the Meat Withholding Period set at 14 days. This means that livestock for human consumption must be withheld from slaughter for 14 days after application of the triflumuron containing product to the animal to ensure that the levels of triflumuron do not exceed the MRL. The inventors believe that the parasiticide composition according to the present 20 invention will also result in a low residue level in the fur, wool and bide of an animal treated with a parasiticide composition of the present invention containing one or more IGR's, particularly IGR's selected from the group consisting of triflumuron, cyromazine, diflubenzuron, fluazuron and methoprene and mixtures thereof.
WO 2005/053746 PCT/AU2004/001688 14 Residue and Safety Trials were carried out using the parasiticide composition according to a preferred embodiment of the first aspect of the invention as a pour-on composition. In one study in which trials were carried out on sheep, the results surprisingly showed that the residue level of the parasiticide composition, according to 5 Example 1, in the perirenal fat of the sheep is about 8 fold lower than the MRL when measured one (1) day after external application. of the composition to the sheep (see Table 5). This result is surprising given that the cument parasiticide products on the market containing comparable amounts of triflumuron (ZAPP@ Bayer) and (Epic@ Jurox) specify that a 14 day withholding period is required before the treated animals 10 can be slaughtered for human consumption," indicating that the residue level of triflumuron is well above the MRL one (1) day after application of the composition to the animal. The result indicate that for livestock treated with a parasiticide composition according to a preferred embodiment of the first aspect of the present invention, the level of IGR will advantageously meet the MRL almost immediately after application 15 to the animal and accordingly will not be subject to the Meat Withholding Period required for livestock treated with the triflumuron parasiticide compositions known to the present inventors that are currently on the market. In another study in which trials were carried out on horses, preliminary results revealed that lice counts conducted 21 days after application of the composition of the 20 invention according to Example 5 and Example 1 resulted in an average lice drop of 99.4% and 97.6 % respectively (see Table 9). The efficacy studies undertaken by the present inventors also indicate that compositions of the invention containing lower concentrations of IGR are as effective as compositions containing higher concentrations of IGR in controlling lice on sheep. 25 For example, the inventors have found that compositions containing 1.0 g/L Triftlumuron (0.1% w/v) and 0,4 g/L alpha-oypermethrin (0.04% w/v) (e.g see Example 7) control the lice counts over a 140 day period as effectively as compositions containing 25 g/L Triflumuron (2.5% w/v) (e.g see Example 1). The results shown below in Table 8 indicate that a 10 fold reduction in the amount of active dosed to the 30 sheep is as effective in reducing the lice to a levelof control over a period of 140 days. An additional benefit of the present invention is it's reduced loading on the waste water from the effluent of textile scouring plants. For instance, with reference to Table 7, the inventors have surprisingly found that when Triflumuron (0.1% w/v) (according to the composition described in Example 8) is used as the IGR in a solvent 35 composition of the present invention, the level of Triflumuron in the wool of a sheep was found to be 5.5 - 6.0 fold less (based on comparison of averages from each sample WO 2005/053746 PCT/AU2004/001688 15 group) than the level of insecticide from a composition containing Triflumuron (2.5% w/v) according to Example 1. Accordingly, using a lower concentration of triflumuron in the composition of the invention is as effective as a composition of the invention containing higher 5 concentrations of triflumuron and has resulted in reduced loading of IGR in the waste water from the effluent of a textile scouring plant. The present inventors have surprisingly found that the parasiticide composition of the present invention provides a composition that is efficacious against !ice at low levels of active, is minfast and reduces the residue loading in the wool of a sheep being 10 treated with such a composition. This has been achieved by providing a parasiticide composition comprising one or mote solvent-combinations, one or more emollients and aqueous carrier and optionally one or more surfactant combinations. The term rainfast, will be understood to mean that the IGR has a higher tolerance to water when the dosed animal is exposed to rain or the animal is wet upon application. The IGR and SP are 15 fully solubilised in the parasiticide composition of the present application and improves the tolerance of the IGR to water. The inventors believe that this water tolerance reduces the amount of precipitated IGR around the point of application and allows the active to spread further around the body thereby improving it's efficacy. This improved efficacy allows the active concentration to be reduced, which in turn reduces 20 the amount of residue on the animal. Without being bound by theory, it is believed that the em-nollient plays a vital role in the parasiticide composition of the present invention by aiding solubilisation of the IGR and optionally SP and helping the IGR or IGR/SP combination to stay close to the skin as well as along the length of the wool staple. The improvement in the solubility 25 of the IGR or IGRISP combination has allowed for a prolonged release of the IGR or IGR/SP combination, thus allowing the amount of active required to be effective to be reduced. The formulation of the present invention is lipophilic and accordingly, the composition of the present invention has a tendency to solubilise well with the wool 30 wax. Without being bound by theory, the present inventors believe that the composition of the present invention, being lipophilio, has a high tolerance to water and accordingly allows the active to move freely throughout an aqueous environment.. Throughout this specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated 35 element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
WO 2005/053746 PCT/AU2004/001688 16 Modes for Carrying out the Invention In order to better understand the nature of this invention, a number of examples will now be described. 5 (A) Examples of parasiticide compositions: Example 1 U~ Triflumuron IOR 25 Cetyl acetate/lanolin acetate/ Emollienteomollient/ 5 Polysorbate 80 surfactant N-methylpyrrolidone solvent 290 dipropyleneglycol monomethyl ether solvent q.s to 1L The composition in Example 1 was prepared by dissolving the triflumuron in N methylpyrrolidone and dipropyleneglycol monomethyl ether, followed by the addition 10 of cetyl acetate, lanolin acetate and Polysorbate 80. Example 2 A" . ': ' - . ..... ..... .. .. ,.., ........ . Triflumuron IGR 25 Myritol 318 emollient 20 Cetiol A emollient 50 N-methylpyrrolidone solvent 290 dipropyleneglycol monomethyl ether solvent q.s. to 1L The composition in Example 2 w s prepared by dissolving the triflumuron in N 15 mnethylpyrrolidone and dipropyleneglycol monomethyl ether, followed by the addition of Cetiol A and Myritol 318. Example 3 Cyromazine IGR 20 Ce~yl Alcohol emollient 5 Dipropyleneglyrol monomethyl ether solvent q.s. to IL Eucalyptus oil fragrance 35 WO 2005/053746 PCT/AU2004/001688 17 The composition in Example 3 was prepared by dissolving the cyromazine in dipropyleneglycol monomnethyl ether, followed by the addition of the emollient and fragrance. Dipropyleneglycol monoethyl ether was added to make up to volume 5 Example 4 Ditlubenzuron IGR 25 Palmitic acid isopropyl ester emollient 2 Glycol ether solvent q.s. The composition in Example 4 was prepared by dissolving the Diflubenzuron Glycol ether, followed by the addition of the emollient. 10 Example 5 Triflumuron IGR 2.3 Alpha Cypermethrin Synthetic Pyrethrin 0.95 Cetyl acetate/lanolin acetate/ Emollientlemollient/ 5 Polysorbate 80 surfactant Glycol ether . solvent 500 Aromatic hydrocarbon solvent q.s D-limonene Fragrance 50 The composition in Example 5 was prepared by dissolving the triflumuron and alpha-cypermethrin in glycol ether and part of the aromatic hydrocarbon, followed by the addition of the emollient, fragrance and the remainder of the solvent. 15 Ex_anje..6 _ _ _ _ _ _ _ _ _ ... . . . ., ' ' • , t. . ... . . .. ... . :,,..... ',v',o,. "j%: " . ." Triflumuron IGR 25 Alpha Cypermethrin Synthetic Pyrethrin 10 Cetyl acetate/lanolin acetate/ Emollient/emollient/ 5 Polysorbate 80 surfactant N-nmethylpyrrolidone solvent 290 dipropyleneglycol monomethyl ether solvent q.s to 1L WO 2005/053746 PCT/AU2004/001688 18 The composition in Example 6 was prepared by dissolving the triflumuron and alphacypermethrin in N-methylpyrrolidone and dipropyleneglycol monomethyl ether, followed by the addition of cetyl acetate, lanolin acetate and Polysorbate 80. 5 Example 7 Triflumuron IGR 1 Alpha Cypermnnethrin Synthetic Pyrethrin 0.4 Cetyl acetate/lanolin acetate/ Emollientlemollient/ 5 Polysorbate 80 surfactant N-methylpyrrolidone solvent 290 dipropyleneglycol monomethyl ether solvent q.s to 1L The composition in Example 7 was prepared by dissolving the triflumuron and alphacypermethrin in N-methylpyrrolidone and dipropyleneglycol monomethyl ether, followed by the addition of cetyl acetate, lanolin acetate and Polysorbate 80,. 10 Example 8 Triflumuron IGR 1 Cetyl acetate/lanolin acetate/ Emollient/emollient/ 5 Polysorbate 80 surfactant N-methylpyrrolidone solvent 290 dipropyleneglycol mouomethyl ether solvent q.s to 1L The composition in Example 8 was prepared by dissolving the triflumuron in N methylpyrrolidone and dipropyleneglycol monomethyl ether, followed by the addition 15 of cetyl acetate, lanolin acetate and Polysorbate 80. (B) Dose Volume Calculations As previously noted, an "effective amount of parasiticide composition" may be achieved using a dose volume that is calculated using (i) the weight of the animal or (ii) 20 the surface area of the animal. Table 3 provides dose volumes calculated on (i) the weight of the animal for a composition according to Example 1. It can be seen that for an animal weighing <10 WO 2005/053746 PCT/AU2004/001688 19 kg and up to 95 kg, seven different dose volumes are required to effectively administer the composition to each animal. Table 3: Composition containing Triflumuron (25 g/L) S according to Example 1: Body weight of animal Dose volume (mL): (kg): 5 10 10 11-20 12 21-30 15 31-55 20 56-75 25 76-85 30 86-95 35 5 For weights above 95 kg an additional 5 mL per 10 kg is added. Using (ii), it has been found that one dose volume of the parasiticide composition may be used to cover a wider range of surface areas. 10 The approximate surface area (m) of animal weighing between 8 and 120 kg was derived from the following equation: *Approximate surface area (m 2 ) = 10.1 x (weight in grams
)
1 10,000 15 * D C Plumb (ed) (1999) Veterinary Drug Handbook 3rd edition, Iowa State University Press, Ames. 750 pages The following dose volumes as shown in Table 4 are for a composition of the invention 20 according to Example 5 and have been calculated based on the surface area of the animal rather than the body weight. For convenience of the end user, the surface area calculations were converted back to a weight range in kg. It can be seen that for an animal weighing 20 kg and up to 104 kg, only four different dose volumes are required to effectively administer the composition to each animal.
WO 2005/053746 PCT/AU2004/001688 20 Based on the above, calculating the dose volume based on (ii) the surface area provides a more convenient dosage regime for the end user when the composition is required to be administered to a number of animals of varying weight. S Table 4: Composition containing Triflumuron (2.3 g/L) according to Example 5 Body weight of animal Dose volume (mL): (kg): _ 20 10 21-40 20 41-80 30 81-104 40 For weights above 104 kg an additional 10 mL is added. (C) Residue level data 10 The Maximum Residue Limits (MRL) Standard published by the Australian Pesticides and Veterinary Medicines Authority set the MRL for triflumuron in sheep meat in the fat at 2 mg/kg (or 2 ug/g). Residue and Safety Trials were carried out on sheep using the composition of Example 1 as a pour-on composition. The improved parasiticide composition 15 according to Example 1 was applied at a concentration of 27.3 (mg/kg of Body Mass) via an applicator gun to the skin of a sheep in a manner known to be effective in applying liquid parasiticides to an animal. One (1) day after application of the composition to the sheep, the sheep was slaughtered and the level of tiflumuron in the perirenal fat of the sheep was determined using known methods. Surprisingly, the 20 residue level of triflumuron in the perirenal fat of the sheep was found to be approximately 0.2 mg/kg, one (1) day after application of the composition to the sheep. This is about 8 times less than the MRL set by the Australian Pesticides and Veterinary Medicines Authority (A.P.V.M.A.) The maximum residue found was 0.454 which is approximately 4.5 times less that the MRL set by the A.P.V.M.A. The results are 25 shown in Table 5 and 6 show the data from 0 -10 days and 10 - 66 days respectively.
WO 2005/053746 PCT/AU2004/001688 21 Table S. Contents of Triflumuron in Kidney, muscle, peri-renal and backfat from sheep treated with a composition according to Example 1 (2.5%w/v Triflumuron) : 0 - 10 Days Slaughter. Sheep # Triflumuron in Triflumniuron in Triflumuron in TriflUmuron in Kidney (pg/g Muscle (g/g peri-renal fat backfat (pg/g kidney tissue) muscle) (pg/g fat tissue) fat tissue) Group 1: Control, No Treatment 3350 ND ND ND ND 5235 ND ND ND ND Group 2: Triflumuron, 1 day sacrifice 2279 ND ND 0.291 0.053 2283 ND ND 0.262 0.062 2289 ND ND 0.351 0.216 5236 ND ND 0.213 0.056 5239 ND ND 0.177 0.037 5259 ND ND 0.251 0.033 Group 3: Triflumuron, 5 day sacrifice 2280 ND ND 0.422 0.252 2282 N ND 0.514 0.323 3392 ND ND 0.349 0.356 3396 ND ND 0,293 .- 0.186 5233 ND ND 0.231 0.210 5238 N ND 0,217 0.236 Group 4: Tritlumuron, 7 day sacrifice 2813 ND ND 0.385 0.219 3327 ND ND 0.454 0.312 3391 ND ND 0.294 0.322 5234 ND ND 0.252 0,163 5258 IND N 0.197 0.182 5260 ND ND 0,282 0.176 Group 5: Triflumuron, 10 day sacrifice 3328 ND ND 0.285 0.256 3393 ND ND 0.146 0.102 3394 ND. ND 0.193 0.136 WO 2005/053746 PCT/AU2004/001688 22 5231 ND ND 0.324 0.237 5237 ND ND 0.165 0.153 5240 D ND 0.130 0.112 Table 6. Contents of Triflumuron in Kidney, muscle, peri-renal and backfat from sheep treated with a composition according to Example 1 (2.5%w/v Triflumuron):. 10 - 66 Days Slaughter. 5 Sheep # Triflumuron in Triflumuron in Triflumuron in Triflumuron in Kidney (pg/g Muscle (pg/g peri-renal fat backfat (pgfg kidney tissue) muscle) (pg/g fat tissue) fat tissue) Group 1: Control, No Treatment 5022 ND ND ND ND 5027 ND ND ND ND Group 2: Triflumuron, 10 day Sacrifice 5009 ND <LOQ 0.099 0.130 5014 ND 0.168 0.182 5025 ND <LOQ 0.164 0.152 5057 ND <LOQ 0.303 0.311 5062 ND <LOQ 0.159 0.162 5066 ND <LOQ 0.212 0.203 Group 3: Triflumuron, 14 day Sacrifice 5005 ND ND 0.161 0.153 5008 ND ND 0.265 0.108 5030 ND ND 0.114 0.121 5051 ND <LOQ 0.149 0.104 5063 ND <LOQ 0.11 0.118 5064 ND <LOQ 0,189 0.203 Group 4: Trflumuron, 21 day Sacrifice 5010 ND <LOQ <LOQ 0.053 5013 ND <LOQ 0.075 0.07 5024 ND <LOQ 0.079 0.115 5026 ND <LOQ 0.278 0.210 5056 ND <LOQ 0.171 0.141 WO 2005/053746 PCT/AU2004/001688 23 5061 N D 0.119 0.170 Group 5: Triflumuron, 42 day Sacrifice 5003 ND ND 0.083 ND 5011 ND ND 0.129 0.091 .5018 ND <LOQ . 0.223 0.108 5054 D ND <LOQ ND 5067 ND ND 0.065 <LOQ 5068 ND ND 0.097 <LOQ Group 6! Triflumuron, 60 day Sacrifice 5006 ND ND <LOQ <LOQ 5015 ND ND <LOQ ND 5017 ND ND <LOQ <LOQ 5019 ND ND <LOQ ND 5058 ND ND <LOQ <LOQ 5065 ND ND <LOQ ND Group 7: Triflumuron, 66 day Sacrifice 5001 ND ND <LOQ ND 5002 ND ND <LOQ <LOQ 5023 ND ND <LOQ <LOQ 5028 ND ND <LOQ <LOQ 5029 ND ND <LOQ <LOQ 5055 ND ND <LOQ ND ND -no data . LOQ=Limit of Quantation Wool residue results: 5 Wool residue studies were conducted 140 and 168 days after treatment of sheep with compositions of the invention and the average concentration of triflumurou residue remaining in the wool was calculated. Table 7 provides results for high and low concentrations oftriflumuron in compositions according to the invention, WO 2005/053746 PCT/AU2004/001688 24 Table 7 -Wool Residue Results: Triflumuron Time (# Triflumuron Triflumuron Wool concentration: days from formulation Residue Applicatio concentration concentration n) (mg/mL) (Tg/kg) High Triwlumuron concentration 2.5% wiv triflumuron 140 25 22 (Examplel 1) 1023 2.5% w/v triflumuron 140 25 32 (Example 1) 2.5% wlv triflumuron 140 25 36 (Example 1) 2.5% w/v triflumuron 140 25 46 (Example 1) 2.5% w/v tritlumuron 140 25 32 (Example 1) 2.5% w/v triflurouron 140 25 34 (Example 1) Average 34 Low Triflumuron concenutraton 0.1%w/v triflaMuron 168 1 2.6 (Example 8) 0. 1%w/v triflumuron 168 1 1.1 (Example 8) O, 1%w/v triflumuron 168 1 2 (Example 8) Average 1.9 5 (D) Efficacy Studies The efficacy studies undertaken by the present inventors indicate that compositions containing 1.Og/L Triflumuron (0.1% w/v) (according to Example 8), 1.0 g/L Triflumuron (0.1% w/v) and 0.4 g/L alpha-cypermethrin (0.04% w/v) (according to 10 Example 7) control the lice counts over a 140 day period as effectively as compositions according to the invention with higher concentrations of triflunmuron, specifically, 25 g/L triflumuron (2.5% w/v) according to Example 1 and 25 g/L Triflumuron (2.5% w/v) and 10 g/L alpha-cypermethrin (1.0% w/v).(according to Example 6). The results shown below indicate that a 10 fold reduction in the amount of active dosed to the 15 sheep is as effective in reducing the lice to a level of control over a period of 140 days. The results are shown in Table 8.
WO 2005/053746 PCT/AU2004/001688 25 Table 8: Treatment Active Triflumuron Alpha Volume of 140 Day % with Dose (mg) eypermethrin Dose (niL) Drop in composition Dose (mg) lice from according day zero to: level Example 1 Triflumuron 500 0 20 100 (2.5% wlv) Example 6 Triflumuron 500 200 20 99.9 (2.5% w/v) & Alpha cypermethrin (1% w/v) Example 7 Triflumuron 50 20 50 99.9 (0.1% w/v) & Alpha cypermnnethrin (0.04% w/v) Example 8 Trifluinuron 50 0 50 99.3 (0.1% w/v) Efficacy in horses 5 Table 9 shows the result on lice count 21 days after applying the composition of the invention according to Example 5 and Example 1 to horses. These preliminary results reveal that lice counts conducted 21 days after application resulted in an average lice drop of 99.4% and 97.6 % respectively. 10 WO 2005/053746 PCT/AU2004/001688 26 Table 9: Horse # Treatment Lice Count % Lice Drop Day 0 Day 21 1* Untreated 205 38 81.5 2 Untreated 144 89 38,2 3 Untreated 86 58 32.6 4 Untreated 149 35 76.5 5 Untreated 80 40 50.0 6 Untreated 45 22 51.1 7 Untreated 178 186 -4,5 AM mean 126.7 66,9 46.5 8 Example 5 263 0 100 9 Example 5 166 0 100 10 Example 5 729 21 97.1 11 Example 5 74 1 98.6 12 ExampleS 31 0 100 13 Example 5 86 0 100 14 Example 5 62 0 100 AM mean 201.6 3.1 99.4 15 Example 1 200 11 94.5 16 Example 1 63 0 100.0 17 Example 1 112 0 100.0 18 Example 1 104 12 88.5 19 Example 1 35 0 100.0 20 Example 1 95 0 100.0 21 Example 1 78 0 100.0 AM mean 98.1 3.3 97.6 E) Rainfast Testing 5 Testing was conducted on thirty (30) mixed lousy merino sheep following treatment with a Triflumuron formulation as backline pour-ons, followed by simulated WO 2005/053746 PCT/AU2004/001688 27 rainfall of 20 mm one hour after and one our before application. The formulation as described in Example 1 was used in the study. Sheep were housed outdoors for a duration of the study and lice counts were carried out using a standard technique at 28, 56, 98 and 140 days after application. 5 All treatment groups showed good activity against heavily infested lousy sheep. By day 140, no lice were found on animals treated with the composition of Example 1 treated wet. Only a single adult louse could be located on one sheep in the group in which the sheep were treated with the composition of Example 1 followed by wetting the animal. By day 56 no immature lioe were found on any of the treated sheep. Both 10 the dry and wet untreated control groups experienced a decrease in lice numbers at day 28 but by day 140 the number had begun to increase. The results are detailed in Table 10. Table 10 - Rainfast Test Results: .15 Sheep Weight Lice Count: Id kg Day 0 Day 28 Day 56 Day 98 Dayl40 Dry animal treated with formulation according to Example 1 1 90 44.8 349 22 5 0 0 2 155 42.8 800 33 14 1 0 3 389 45 674 33 10 0 0 4 443 43.4 800 42 11 2 0 5 449 44.8 509 7 5 1 0 6 507 43.2 792 54 -10 0 0 AM 44 654 31.8 9.2 0.7_ 0.0 Dry animal treated with formulation according to Example 1 and animal then wet 7 12 45 800 64 22 1 0 8 22 49.4 698 21 21 1 0 9 159 48.6 571 16 6 0 0 10 164 53.5 800 17 8 0 0 11 298 48.6 800 34 9 1 1 12 3833 48.6 413 7 4 0 0 AM 49 680.3 26.5 11.7 0.5 0.2 WO 2005/053746 PCT/AU2004/001688 28 Wet animal treated with formulation according to Example 1 13 58 49.6 686 9 11 0 0 14 143 49.4 709 12 8 0 0 15 316 52.5 746 30 12 0. 0 16 334 50.5 760 11 6 0. 0 17 337 49.6 749 56 15 0 0 18 446 49.6 800 30 14 2 0 AM 50.2 741.1 24.7 11 0.3 0.0 Dry ControlI 19 59 52.5 595 120 218 132 160 20 322 59.5 800 662 444 477 632 21 374 53.5 526 148 51 89 173 22 448 53 623 145 100 171 329 23 3824 53,5 779 551 545 422 627 24 3847 . 53 800 405 267 319 560 Wet control AM 54.2 687.2 338.5 270.8 268.3 413.5 25 112 58.5 660 142 134 94 414 26 116 54 708 105 77 126 282 27 365 60 800 178 125 188 337 28 505 61.5 800 153 215 477 690 29 552 59.5 800 613 646 614 800 30 597 56 700 191 113 106 402 Ingredient Availability: Table 11 - Insect Growth Re gulators (IGR) ii* ......... . Triflumuron Pacific Resource Cyromazine Pacific Resource Diflubenzuron Pacific Resource Methoprene Pacific Resource 5 WO 2005/053746 PCT/AU2004/001688 29 Table 12 - Emollients panlmitic acid isopropyl ester; steric acid isopropyl ester; Pelemol CL, Henkcel/Cogrnd Wickenol 507, Cutina CP, Ritacetyl, , Isopropyl palmitate, Isopropyl stearate and Eutanol 0; lanolin oil; Lantrol I-HP, Ritalan, Myritol 32, Myritol 318; Euperlan PK; isooctyl stearate, laurie acid hexyl ester, butyl adipate, myristyl myristate cetyl acetate; lanolin acetate; cetyl palmitato; octyl palmitate; Cotiol Bronson & 868, Cetiol A, Cetiol B, Cogesoft C and Cetiol MM Jacobs Table 13 - Surfaetants I,' .'. ? " " : "' ";. . :: .J. . i :n.,.ll .' tj L..: ' ,,, .'. ': . '::.::...: "*.".- *. ; " , "' l', Terio N9, Teric N20, Teric NOO1, Teric 9A2, Teric 16A16, Terio 13M15, Teria 18M20 and Teric 380 . ICI Cremophor EL BASF Corporation Aeconon CA-5 Karishamus USA Inc Polycol 5 and Polycol 40 CRODA Polysorbate 20 (trade name Tween 20), Polysorbate 60 (trade name Tween 60) and Polysorbate 80 (trade name Tween 80) ICI Hodag SML Calgene Span 25. ICI 5 Table 14 - Solvents Dipropylenegmlycol monomethyl ether ICI N-methyl pyrrolidone APS Butyl di-icinol, glycol ether ICI Solvesso 200, Solvesso 150 Redox Chemicals 10 WO 2005/053746 PCT/AU2004/001688 30 Table 15 - Synthetic Pyrethroids Alpha cyprnethrin ISAGRO Delta cyper-methrin ISAGRO Table 16 - Perfumes .5 D-Linmonene Bronson & Jacobs Orange Oil Bronson & Jacobs Tea Troee Oil Bronson & Jacobs Eucalyptus Oil Broison & Jacobs Combination of emollient/surfactant The emollient/surfaectant mixture, cetyl acetate/lanolin acetate/Polysorbato 80, is available from Ethnichem. 10 It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodimrnents without departing from the spirit or scope of the invention as broadly described. The present embodiments arc, therefore, to be considered in all respects as illustrative and not restrictive.
Claims (27)
1. A water washable parasiticide composition comprising: 0.01 - 30% w/v of one or more insect growth regulators; 0.01 - 20% w/v of one or more emollients; 5 the balance being one or more organic solvents.
2. The water washable parasiticide composition according to claim 1 wherein the composition fin-rther includes one or more surfactants.
3. The water washable parasiticide composition according to claim 1 or 2 wherein the composition includes a surfactant in an amount of about 0.005 - 30%w/v. 10 4. The water washable parasiticide composition according to any one of claims 1-3 wherein the composition includes one or more synthetic pyrethroids.
5. The water washable.parasiticide composition according to any one of claims 1-4 wherein the composition includes one or more synthetic pyrethroids in an amount of about 0.01-5% w/v. 15 6. The water washable parasiticide composition according to any one of claims 1 5, wherein the one or more insect growth regulators are selected from the group consisting of triflumuron, cyromazine, diflubenzuron, fluazuron, methoprene and umixtures thereof.
7. The water washable parasiticide composition according to any one of claims 1-6 20 wherein the insect growth regulator is triflumuron.
8. The water washable parasiticide composition according to any one of claims 1-7 wherein the one or more insect growth regulators are included in the composition in a concentration of about 0.1-30% w/v.
9. The water washable parasiticide composition according to any one of claims 1-8 25 wherein the one or more insect growth regulators are included in the composition in a concentration of about 0.1-20%w/v.
10. The water washable parasiticide composition according to any one of claims 1-9 wherein the one or more insect growth regulators are included in the composition in a concentration of about 0.1-10% w/v. 30 11. The water washable parasiticide composition according to any one of claims 1 10 wherein the one or more insect growth regulators are included in the composition in a concentration of about 0.1-5% w/v.
12. The water washable parasiticide composition according to any one of claims 1 11 wherein the one or more emollients are selected from the group consisting of fatty 35 acid esters; a mixture of glycol distearate, laureth-4 and cocamidopropyl betaine; a mixture of sodium laureth sulfate, glycol distearate and cocamide MEA; a mixture of WO 2005/053746 PCT/AU2004/001688 32 glycol distearate, sodium laureth sulfate, cocamide MEA and Laureth-9; a mixture of triethylene glycol distearate and sodium laureth sulfate; long chain fatty alcohols; lanolin oil and derivatives thereof; triglycerides; sterols; distilled wool wax alcohols and mixtures thereof. 5 13. The water washable parasiticide composition according to claim 12 wherein the fatty acid esters are selected from the group consisting of cetyl acetate, cetyl palmitate, myristic acid isopropyl ester, palhnitic acid isopropyl ester, steric acid isopropyl ester, cetyl lactate, acetylated lanoline, cetyl pairnlmitate, octyl stearate, isooctyl stearate, laurie acid hexyl ester, butyl adipate, dibutyl adipate, octyl palmitate and myrtistyl myristate, 10 myristyl lactate, and glycol isostearate, caprylio acid ester and capric acid ester.
14. The water washable parasiticide composition according to any one of claims 12 or 13 wherein the long chain fatty alcohols are selected from the group consisting of n octyl dodecanol, cetyl alcohol, cetyl stery] alcohol and oleyl alcohol.
15. The water washable parasiticide composition according to any one of claims 12 15 14 wherein the triglycerides are selected from the group consisting of caprylic triglyceride, capric triglyceride and glycol isostearate.
16. The water washable parasiticide composition according to any one of claims 12 15 wherein the sterols are selected from the group consisting of beta- sitosterol, campesterol, stigmasterol. 20 17. The water washable parasiticide composition according to any one of claims 1 16 wherein the one or more emollients are selected from the group consisting of fatty acid esters having an alcohol component with a chain length of Cl - C2 or C4-C18; fatty acid esters having an acid component with a chain length of C4 - C13 or C015 C30; a mixture of glycol distearate, laureth-4 and cocan-idopropyl betaine; a mixture of 25 sodiurn laureth sulfate, glycol distearate and cocamide MEA; a mixture of glycol distearate, sodium laureth sulfate, cocamide MEA and Laureth-9; a mixture of triethylene glycol distearate and sodium laureth sulfate; long chain fatty alcohols; lanolin oil; triglycerides; sterols; distilled wool wax alcohols and mixtures thereof.
18. The water washable.parasiticide composition according to claim 17 wherein the 30 fatty acid esters are selected from fatty acid esters having an alcohol component with a chain length of C4-C 18 and/or fatty acid esters having an acid component with a chain length of C8 - C13 or C15 - C24.
19. The water washable parasiticide composition according to claim 17 or 18 wherein the long chain fatty alcohols have a chain length CS - C18. WO 2005/053746 PCT/AU2004/001688 33
20. The water washable parasiticide composition according to any one of claims 17 19 wherein the triglycerides have a vegetable fatty acid component with a chain length of C8-C12.
21. The water washable parasiticide composition according to claim 18 wherein the 5 fatty acid esters having an alcohol component with a chain length of C4-CI8 are selected from the group consisting of cetyl acetate, cetyl palmitate, lanoline acetate and mixtures thereof.
22. The water washable parasiticide composition according to claim 18 wherein the fatty acid esters having an acid component with a chain length of C8 - 013 or C15 10 C24 are selected from the group consisting of palmitic acid isopropyl ester, steric acid isopropyl ester, caprylic acid ester and capric acid ester, laurie acid hexyl ester and mixtures thereof
23. The water washable parasiticide composition according to any one of claims claim 17-22 wherein the long chain fatty alcohols are selected from the group 15 consisting of n-octyl dodecanol, cetyl alcohol, cetyl steryl alcohol, oleyl alcohol and mixtures thereof.
24. The water washable parasiticide composition according to any one of claims 17 23 wherein the triglycerides are selected from the group consisting of caprylic triglyceride, capric triglyceride, glycol isostearate and mixtures thereof. 20 25. The water washable parasiticide composition according to any one of claims 17 24 wherein the sterols are selected from the group consisting of beta-sitosterol, campesterol, stigmasterol and mixtures thereof.
26. The water washable parasiticide composition according to any one of claims 1 25 wherein the one or more emollients are selected from the group consisting of lanolin 25 acetate, cetyl acetate, lauric acid hexyl ester, caprylic/capric triglyceride, palmitic acid isopropyl ester, cetyl alcohol and mixtures thereof,
27. The water washable parasiticide composition according to any one of claims 1 26 wherein the one or more emollients are present in a concentration of about 0.1-20 %w/v. 30 28. The water washable parasiticide composition according to any one of claims 1 27 wherein the one or more emollients are present in a concentration of about 0.02 I 0%w/v.
29. The water washable parasiticide composition according to any one of claims 1 28 wherein the one or more emollients are present in a concentration of about 0.05 35 5%w/v. WO 2005/053746 PCT/AU2004/001688 34
30. The water washable parasiticide composition according to any one of claims 1 29 wherein the one or more organic solvents are selected from the group consisting of aliphatic and/or aromatic alcohols; glycols; aliphatic and/or aromatic aldehydes; ketones; aliphatic and/or aromatic hydrocarbons; polyols; glycol ethers; glycol ether 5 acetate; Cl - CS alkyl pyrrolidones.; aliphatic and/or aromatic esters; and mixtures thereof
31. The water washable parasiticide composition according to claim 30 wherein the aliphatic alcohols are selected from the group consisting of methanol, butanol, isopropyl alcohol and mixtures thereof; the aromatic alcohol is benzyl alcohol; the 10 glycols are selected from the group consisting of polyethylene glycols, polypropylene glycols and mixtures thereof; the aliphatic hydrocarbon is octane; the aromatic hydrocarbons are selected from the group consisting of toluene, xylene and mixtures thereof; the ketones are selected from the group consisting of acetone, 3-buten-2-one, butanone, cyclohexanone and mixtures thereof; the glycol ethers are selected from the 15 group consisting of dipropyleneglycol monomethyl ether, butyl icinol, butyl di-icinol and mixtures thereof; the Ci-Cs alkyl pyrrolidones are selected from the group consisting of N-methyl pyrrolidone, I-octyl-2-pyrrolidinone, lauryl pyrrn'olidone and. mixtures thereof; the aromatic ester is benzyl benzoate; and the aliphatic esters are selected from the group consisting of methyl acetate, ethyl acetate and mixtures 20 thereof.
32. The water washable parasiticide composition according to any one of claims 1 31 wherein the one or more organic solvent is selected from one or more of the group consisting of dipropyleneglycol monomethyl ether, N-methyl pyrrolidone, benzyl alcohol, toluene, xylene, benzyl benzoate, cyclohexanone,-butyl di-icinol, ethyl acetate 25 and mixtures thereof.
33. The water washable parasiticido composition according to any one of claims 1 32 wherein the one or more organic solvent are present in an amount of about 10
99.9% w/v. 34. The water washable parasiticide composition according to any one of claims 1 30 33 wherein the one or more organic solvent are present in an amount of about 20 99.5% w/v. 35. The water washable parasiticide composition according to any one of claims 1 34 wherein the one or more organic solvent are present in an amount of about 30 99,5% w/v. WO 2005/053746 PCT/AU2004/001688 35 36. The water washable parasiticide composition according to any one of claims 1 35 -wherein the one or more surfactants are one or more non-ionic surfactants and/or one or more anionic surfactants. 37. The water washable composition according to claim 36 wherein the one or more 5 non-ionic surfactants is selected from the group consisting of C8-C10O alkylphenol ethoxylates, such as ethoiylated nonylphenol; C9-C17 alcohol ethoxylates; C8-C20 alkcyl amine ethoxylates; castor oil ethoxylates; lanolin alcohol ethoxylates; sorbitan fatty acid ester ethoxylates; sorbitan fatty acid esters; alkyl aryl sulphonates and mixtures thereof; and wherein the one or more anionic surfactants are selected from the 10 group consisting of C9 - C13 alkyl benzene sulphonates and C9 - C13 alkyl sulphate and mixtures thereof. 38. The water washable parasiticide composition according to any one of claims 1 37 wherein the surfactant is one or more sorbitan fatty acid esters. 39. The water washable parasiticide composition according to any one of claims 1 15 38 wherein the one or more surfactants is present in an amount of about 0.1- 30%w/v. 40. The water washable parasiticide composition according to any one of claims 1 38 wherein the one or more surfactants is present in an amount of about 0.01 - 20% w/v. 41. The water washable parasiticide composition according to any one of claims 1 20 38 wherein the one or more surfactants is present in an amount of about 0.02-10%. 42. The water washable parasiticide composition according to any one of claims 1 38 wherein the one or more surfactants is present in an amount of about 0.05-5% w/v. 43. The water washable parasiticide composition according to any one of claims 1 38 wherein the composition is in the form of an emulsifiable concentrate. 25 44. The water washable parasiticide composition according to claim 43 wherein the emulsifiable concentrate is diluted with water. 45. The water washable parasiticide composition according to any one of claims 1 44 wherein the composition includes one or more synthetic pyrethroids selected from the group consisting of alphacypermethrin, cypermethrin, deltamethrin, permethrin, 30 bifenthrin and eyfluthrin and mixtures thereof. 46. The water washable parasiticide composition according to any one of claims 1 45 wherein the composition further includes one or more fragrances. 47. The water washable parasiticide composition according to any one of claims 1 46 wherein the composition further includes one or more fragrances selected from the 35 group consisting ofessential oils and terpenes and mixtures thereof. WO 2005/053746 PCT/AU2004/001688 36 48. The water washable parasiticide composition according to claim 47 wherein the essential oils are selected from the group consisting of eucalyptus oil, tea tree oil, orange oil, garlic oil and clove oil and the terpenes are selected from the group consisting of d-limnonene, a-pinene, P-pinene, P-myrcene and terpinolene and mixtures 5 thereof. 49. The water washable parasiticide composition according to any one of claims 1 48 wherein the composition further includes one or more fragrances in an amount of about 1 - 5%w/v. 50. A water washable parasiticide composition comprising: 10 0.2 - 10% w/v triflumuron; 0.05 - 5% w/v of one or more emollients selected from the group consisting of lanolin acetate, cetyl acetate, lauric acid hexyl ester, caprylic/capric triglyceride, palmitic acid isopropyl ester, cetyl alcohol and mixtures thereof; 0.05 - 5% w/v one or more surfactants selected from the group consisting of CS 15 C10 alkylphenol ethoxylates, C9-C17 alcohol ethoxylates, C8-C20 alkyl amine ethoxylates, castor oil ethoxylates, lanolin alcohol ethoxylates, sorbitan fatty acid ester ethoxylates, sorbitan fatty acid esters and mixtures thereof; and 0.075- 5% w/v of one or more synthetic pyrethroids selected from the group consisting of alphacypermethrin, cypermethrin, deltamethrin, permethrin, bifenthrin 20 and cyfluthrin and mixtures thereof; 0.5- 5% w/v of one or more fragrances selected from the group consisting of eucalyptus oil, tea tree oil, orange oil, garlic oil and clove oil, d-limonene, a-pinene, f pinene, P-myrcene and terpinolene and mixtures thereof; the balance being an organic solvent, or a mixture of organic solvents selected 25 from one or more of the group consisting of dipropyleneglycol monomethyl ether, N methyl pyrrolidone, benzyl alcohol, toluene, xylene, benzyl benzoate, cyclohexanone, butyl di-icinol and ethyl acetate and mixtures thereof. 51. A water washable parasiticide composition substantially as hereinbefore described with reference to any one of Examples 1-8. 30 52. A method of treating parasites in/on an animal, the method comprising administering to the animal an effective amount of the parasiticide composition according to any one of claims 1-51. 53. The method according to claim 52 wherein the parasiticide composition is administered to the animal in a dosage volume of about 10-100 mL per 50 kg of body 35 weight of animal WO 2005/053746 PCT/AU2004/001688 37 54. Use of the parasiticide composition according to any one of claims 1-51 in the preparation of a medicament for the treatment of parasites in/on an animal. 55. A method of cleaning a device containing a water washable parasiticide composition according to any one of claims 1-51, the method comprising washing the 5 device with an aqueous solution in a manner so as to effectively remove substantially all of the composition from the device.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2004294226A AU2004294226A1 (en) | 2003-12-04 | 2004-12-02 | Improved parasiticide composition |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2003906726 | 2003-12-04 | ||
AU2003906726A AU2003906726A0 (en) | 2003-12-04 | Improved parasiticide composition | |
PCT/AU2004/001688 WO2005053746A1 (en) | 2003-12-04 | 2004-12-02 | Improved parasiticide composition |
AU2004294226A AU2004294226A1 (en) | 2003-12-04 | 2004-12-02 | Improved parasiticide composition |
Publications (1)
Publication Number | Publication Date |
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AU2004294226A1 true AU2004294226A1 (en) | 2005-06-16 |
Family
ID=36660034
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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AU2004294226A Abandoned AU2004294226A1 (en) | 2003-12-04 | 2004-12-02 | Improved parasiticide composition |
Country Status (1)
Country | Link |
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AU (1) | AU2004294226A1 (en) |
-
2004
- 2004-12-02 AU AU2004294226A patent/AU2004294226A1/en not_active Abandoned
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