VETERINARY FORMULATION

Abstract: A wool grease fraction having a substantially neutral oxidation profile and a formulation for topical application to wool producing animals, said formulation comprising a light stable active agent in a vehicle comprising a wool grease fraction having a substantially neutral profile. A formulation for topical application to wool producing animals, said formulation comprising a light stable active agent in a vehicle comprising at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. Processes for manufacturing the fractions and formulations and methods of controlling pests employing the formulations.

Description: Veterinary Formulation Technical Field This invention relates to a formulation for topical application to animals and to a method for preparing such a formulation. The invention also concerns the use 5 of the formulation in the treatment of animals. Background Art Ectoparasites such as blowfly, lice, itch mite and scab, can seriously affect productivity in the sheep and cattle industries. Typically, ectoparasites are controlled by the topical application of pesticides o such as organophosphates and synthetic pyrethroids. Among other agents which may be used are insect growth regulators, such as benzoyl ureas and triazines. The control agents are usually applied as liquid formulations, by plunge or spray dipping, by jetting with a hand held spray or in a race, or by a back-line spray or pour-on. 5 In the sheep industry the treatment is commonly carried out in early season, ie within 24 hours after shearing (offshears), or, less frequently, later in the season when; the wool is longer. Particularly with early season treatments, it has been found that when applied along the back-line of the animal, the pesticide component of currently available commercial formulations migrates very poorly from the 0 application site. While diffusion may be fairly rapid during the first few days after treatment, typically less than 10% of the applied pesticide diffuses away from the application site within the first 10 days. When applied topically to sheep, pesticides, and many other animal health products, tend to associate with wool grease to form a wool grease/pesticide 5 composition which essentially exists as a discrete, localised layer on wool staples and as the wool grows, so the pesticide-containing layer moves away from the skin surface (the site of for example lice predilection) and contact with the lice or other organisms is reduced or eliminated completely. Apart from reduced efficacy at the application site, a further problem o associated with an essentially immobile deposit of a pesticide in particular is that extensive areas of the fleece may receive concentrations of pesticide which are sub- lethal to pests, and such areas will therefore remain susceptible to damaging invasion by flies, lice and the like. To compensate, it has become common in the industry to apply relatively massive amounts of pesticide, which introduces 5 unwelcome costs, results in the presence of pesticide residues in wool and wool by¬ products and increases the potential of wool scouring liquors to create environmental pollution. There is also an increased risk of shearers and other people handling the treated animals being harmed by exposure to toxic chemicals. As greater pesticide mobility should allow the same pesticidal effect to be achieved by the application of less pesticide than is usual with conventional formulations, solvent-based formulations have received attention in recent times. Unfortunately there has been little success in identifying a solvent which materially 5 enhances the spread of back-line applied pesticides or other active agents. Background of the Invention In the course of searching for a solvent to enhance the spread of back-line applied active agents, particularly pesticides, the inventors were of the opinion that formulations based on wool grease or components of wool grease, when applied to o the sheep, may provide a more mobile deposit of the pesticide allowing the biologically active material to move to the required parts of the fleece. This resulted in isolating the various fractions of wool grease and testing the ability of some of these fractions to enhance the spread of a back-line applied pesticide. Set out as follows are the details known to the inventors of the components of 5 wool grease. Quantities given with respect to the constituents of these classes are of necessity approximate due to differences between the published results presumably reflecting the differing breed, diet, age, environment of the animals from which the wool was obtained and the degree of sophistication of techniques used in such analysis. 0 Wool grease is the lipid material in the fleece recoverable from raw wool by extraction with solvents such as hexane. It is a complex mixture of high molecular weight esters and some free alcohols and acids with a small amount of hydrocarbons. Esters comprise the bulk of wool grease and contain both sterol and wax 5 esters which in turn can be mono or diesters (1,2). Sterol esters are steroids such as but not limited to cholesterol, lanosterol and related sterols (isocholesterol or triterpene alcohols) esterified to higher fatty acid (eg. cholesteryl palmitate). These esters are the major component of wool wax. Wax esters are long chain water insoluble alcohols esterified to higher fatty acids (such as but not limited to palmitic o acid stearyl ester) (1,3). Hydrocarbons are long chain alkanes such as, but again not limited to, octadecane. Wool Grease Alcohols Alcohols consist of cholesterol and triterpene alcohols, aliphatic mono alcohols and alkane-l,2-diols. 5 Sterols and triterpene alcohols These comprise 68-72% of wool grease alcohols with cholesterol as the major steroid present (about 50%) followed by lanosterol and dihydro lanosterol (about 45%). Other isocholesterols may be present in small amounts (4-8). Aliphatic mono alcohols These comprise about 17-22% of wool grease alcohols and consist of normal, iso and anteiso alcohols (4-6). (By "iso" in this specification in connection with both alcohols and acids it is meant branched with terminal isopropyl group and 5 even carbon atom number. By "anteiso" in this specification it is meant branched with terminal isobutyl group and odd carbon atom number.) Normal mono alcohols constitute approximately 2% of total grease alcohols. At least 16 members of this series have been identified and they are present in the chain length range C J4 -C 34 . The major components are C 2 o, C 22 , C 24 and C 26 - o Iso mono alcohols constitute approximately 6.5% of total grease alcohols. At least 11 members of this series have been identified and they are present in the chain length range C 14 -C 36 . The major components are C 20 , C 22 and C 26 - Anteiso mono alcohols constitute the major class in aliphatic mono alcohols 6.5-9% of total grease alcohols. At least 11 members of this series have been s identified and they are present in the chain length range Cπ-C 35 . The major components are C 2 ι, C 25 , C 2 and C 29 - Alkane-1,2 diols These comprise about 8-9% of wool grease alcohols and consist of normal, iso and anteiso 1,2 diols. o Normal 1,2 diols constitute only about 1 % of total grease alcohols. At least 14 members of this series have been identified and they are present in the range Cι 2 -C 26 - The major components are C l6 , Cι 8 and C 2 o- Iso 1,2 diols constitute the major class in aliphatic diols 4-6% of total grease alcohols. At least 9 members of this series have been identified and they are 5 present in the chain length range Cι 4 -C 30 . The major components are C 18 , C 2 o, C 22 and C 2 . Anteiso 1,2 diols constitute about 2% of total grease alcohols. At least 8 members of this series have been identified and they are present in the chain length range C 15 -C 29 . The major components are C 2 ι and C 23 . 0 Wool Grease Acids Wool grease acids consist predominantly of alkanoic, α-hydroxy and ω- hydroxy acids. Each group contains normal, iso and anteiso series of various chain lengths. These acids are almost fully saturated with less than 1 % unsaturated. Wool grease contains approximately equal amounts of acids and alcohols (1, 4-6). 5 Normal acids constitute about 10% of total grease acids. At least 27 members of this series have been identified and they are present in the chain length range C 8 -C 38 . The major components are C 14 , Cι 6 , C 18 , C 2 and C 26 - Iso acids constitute about 22% of total grease acids. At least 17 members of this series have been identified and they fall in the range C 8 -C 0 . The major components are Cι , C 16 , C 18 , C 2 o, C 2 and C 2 6- Anteiso acids constitute the largest group of these acids, about 28 % of total grease acids. At least 18 members of this series have been identified and they are present in the range C 7 -C 1 . The main components are C 13 , Cι 9 , C 2 ι, C 25 and C 27 . Hydroxy acids Number of Chain Length Mjijor % of wool acids components wax acids identified a hydroxy normal 23 0-C32 C16 17 a hydroxy iso 12 Ci2"C3 4 Ci8, C 2 9 hydroxy anteiso 12 C11-C33 C19, C23, C25 3 ωhydroxy normal 14 C22-C36 C30J C32 3 ωhydroxy iso 8 C22-C36 C30, C32 0.5 ωhydroxy anteiso 7 C23-C35 C25» C31 1 unsaturated varies not determined mainly Ciβ, minimal polyhydroxy not C, 8 determined Esterification Monoesters Monoester grease are chiefly of two types (a) fatty acid esters of fatty alcohols and (b) fatty acid esters of sterols. In fresh wool grease monoesters are derived by combination of monocarboxylic acids with steroids, namely, cholesterol and lanosterol and some other triterpene alcohols. Only a small amount of monoesters is derived by combination of simple acid with long chain alcohol. In contrast the alcoholic component of diesters of α-hydroxy acids do not include sterols, they are exclusively long-chain alcohols. In the a, β diesters, normal acids are more abundant than iso-acids which are more plentiful than anteiso acids (7- 10). Diesters Wax and sterol diesters form about a third of total esters and consist of two types: Type 1 consists of 2-hydroxy acid esterified with both a fatty alcohol and a fatty acid. Another variant of this type is where the 2-hydroxy acid is esterified with an unsubstituted fatty acid and a sterol, the latter being predominantly cholesterol (11). Type 2 diesters consist of long chain 1,2 diols in which both hydroxy groups are esterified to unsubstituted fatty acids. Sterol diesters and wax diesters are present in approximately equal amounts (11). The acid component of sterol esters range between C 14 and C 31 with normal, iso and anteiso acids present (4-6). Lanosterol forms at least 24 esters and is esterified mainly by iso acids and anteiso acids particularly in the range C 15 -C 20 (9). Cholesterol forms at least 21 esters and is esterified almost entirely by iso and anteiso acids particularly in the ranges C 19 -C 2 ι and C 25 -C 27 (9). Based on the random combination of acids and alcohols, an almost infinite number of esters may be present (1) but these esters must contain specific combinations and it has been calculated that wool grease must contain at least 8000 mono and diesters (9). In fact, the number could dramatically exceed that in view of more recent work (5,6). Nevertheless it has to be assumed that the most common esters are those formed between the major components. Fatty Acid C No. Systematic name Common name Formula M 4 Butanoic Butyric CH 3 (CH 2 ) 2 COOH 88.1 5 Pentanoic Valeric CH 3 (CH 2 ) 3 COOH 102.1 6 Hexanoic Caproic CH 3 (CH 2 ) 4 COOH 116.1 7 Heptanoic Enanthic CH 3 (CH 2 ),COOH 130.1 8 Octanoic Caprylic CH 3 (CH 2 ) 6 COOH 144.2 9 Nonanoic Pelargonic CH 3 (CH 2 ) 7 COOH 158.2 10 Decanoic Capric CH 3 (CH 2 ) 8 COOH 172.3 11 Hendecanoic Undecyclic CH 3 (CH 2 ) 9 COOH 186.3 12 Dodecanoic Laurie CH 3 (CH 2 ) 10 COOH 200.3 13 Tridecanoic Tridecylic CH 3 (CH 2 )„COOH 214.3 14 Tetradecanoic Myristic CH 3 (CH 2 ), 2 COOH 228.4 15 Pentadecanoic Pentadecylic CH 3 (CH 2 ) t3 COOH 242.4 16 Hexadecanoic Palmitic CH 3 (CH 2 ) 14 COOH 256.4 17 Heptadecanoic Margaric CH 3 (CH 2 ) 15 COOH 270.4 18 Octadecanoic Stearic CH 3 (CH 2 ) 16 COOH 284.4 20 Eicosanoic/Icosanoic Arachidic CH 3 (CH 2 ) 18 COOH 312.5 22 Docosanoic Behenic CH 3 (CH 2 ) 20 COOH 340.5 24 Tetracosanoic Lignoceric CH 3 (CH 2 ) 22 COOH 368.6 26 Hexacosanoic Cerotic CH 3 (CH 2 ) 24 COOH 396.6 28 Octacosanoic Montanic CH 3 (CH 2 ) 26 COOH 424.7 30 Triacontanoic Melissic CH 3 (CH 2 ) 28 COOH 452.8 33 Tritriacontanoic Psyllic CH 3 (CH 2 ) 31 COOH 494.8 35 Pentriacontanoic Ceroplastic CH 3 (CH 2 )3 3 COOH 522.9 Fatty Alcohol C No. Fatty Alcohol Common Name Formula M 10 Decanol decyl alcohol C 10 H 22 O 158.3 12 Dodecanol lauryl alcohol C 12 H 26 O 186.3 14 Tetradecanol myristyl alcohol Ci-jHsoO 214.4 16 Hexadecanol cetyl alcohol CιβH 3 O 242.4 18 Octadecanol stearyl alcohol CιsH 38 θ 270.5 20 Icosanol arachidyl alcohol C 2 oH 4 O 298.5 22 Decosanol behenyl alcohol C 22 H 46 O 326.5 24 Tetracosanol lignoceryl alcohol C 2 H 5 oO 354.6 26 Hexacosanol ceryl alcohol C 26 H 54 O 382.7 28 Octacosanol motanyl alcohol C 8 H 58 O 410.8 30 Tricotanol melissyl alcohol C 3 oH 62 O 438.8 Object of the Invention It is an object of this invention to provide a formulation for topical application to an animal. Definitions "Wool producing animals" when used in this specification means a sheep and includes, but is not limited to, an animal such as a llama, alpaca, goat and rabbit which produces a natural fibre used commercially as a substitute for the wool of sheep; "Pesticide" when used in this specification means a substance for destroying pests which can be detrimental to a wool producing animal and includes, but is not limited to, an acaricide, a bactericide, a fungicide, an insecticide, an anthelmintic agent, an attractant, an anti-viral agent, a wound protectant and a repellant; "Sterol ester" when used in this specification means a compound such as, but not limited to, cholesteryl palmitate or cholesteryl stearate; "Sterol" when used in this specification means a compound such as, but not limited to, cholesterol, triterpene alcohol, lanosterol or dihydrolanosterol; and "Wax ester" when used in this specification means a compound such as, but not limited to, palmitic acid lauryl ester or stearic acid lauryl ester. Disclosure of the Invention The present inventors have found that certain chemically definable fractions of wool grease and the compounds contained therein are unexpectedly effective in promoting the dispersion of active agents, particularly biologically active agents, over skin surfaces. Freshly secreted wool grease is largely non-oxidised, but progressively oxidises on exposure to air. The present inventors have established that certain grease fractions are much more rapidly oxidised than others, and surprisingly that there is a marked correlation between resistance to oxidation and effectiveness in promoting the dispersion of entrained synthetic pyrethroids and like substances over the skin of a treated animal. The dramatic variation in oxidation susceptibility of wool grease fractions, and the discovery of the connection between oxidation susceptibility and lack of diffusion over animal skin, has now made it possible to 5 propose veterinary formulations for topical application which offer comparable or better effect than conventional formulations. In a first embodiment, the invention provides a wool grease fraction having a substantially neutral oxidation profile. In a second embodiment, the invention provides a formulation for topical io application to wool producing animal, said formulation comprising a light stable active agent in a vehicle comprising a wool grease fraction having a substantially neutral oxidation profile. In a third embodiment, the invention provides formulation for topical application to a wool producing animal, said formulation comprising a light stable ι s active agent in a vehicle comprising at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. The invention also includes processes for manufacturing the fractions and formulations and to methods of controlling pests employing the formulations. 20 It is preferred that the fraction substantially comprises triterpene esters containing substantially unoxidised isocholesterols. It is most preferred that the fraction substantially comprises the sterol esters and wax esters (both as herein defined). Substances having similar hydrophilic-lipophilic values and/or oxidation 25 resistant properties to the sterol esters, wax esters, triterpene esters containing substantially unoxidised isocholesterols or analogues thereof may also be used in the formulations of the invention. The preferred vehicle or fraction from wool grease for use in the invention is therefore largely a fresh non oxidised and non polar mixture of sterol esters 3o (typically about 70%), wax esters (typically about 25%) and usually comprising small amounts of substantially unoxidised isocholesterol esters and saturated hydrocarbons. Preferably all free fatty acids, aliphatic fatty alcohols, sterols and oxidised relatively polar compounds are removed by column chromatography. On alkaline hydrolysis (saponification) of sterol esters or wax esters, wool grease 35 alcohols and wool grease acids are the two lipid classes obtained (1, 4-6). The sterol ester and the wax ester may each independently be a monoester or a diester. It is preferred that the sterol ester is of a sterol and a long chain fatty acid and the wax ester is of a long chain insoluble alcohol and a long chain fatty acid. The long chain fatty acid from which each of the sterol ester and the wax ester can be produced preferably contains from 7 to 36 carbon atoms. The alcohol from which the wax ester can be produced preferably contains from 14 to 36 carbon atoms. 5 Generally the higher the concentration of sterol or wax ester in the formulations of this invention the more rapid will be diffusion of the ingredients over skin to which the formulation has been applied. Preferably when the active agent being used is a pesticide, and in particular a synthetic pyrethroid, a pesticide to ester ratio in the range 1:20 to 1:200 will be a suitable basis for most o formulations. The present invention is particularly suitable for the delivery of biologically active agents which are solid or crystalline materials. Typically such agents are pesticides, which include acaricides, antiparasitic agents, insecticides, anthelmintic agents, insect growth regulators, fungicides, antibiotics, anti- viral agents, s attractants, wound protectants and repellents, however, the invention is not to be seen as restricted to use solely with such agents. The pesticides used in formulations according to this invention may be, in particular, pyrethroids or organophosphates. Examples of insect growth regulators which may be used include cyromazine, benzoyl ureas and triazines. Particular 0 examples of suitable biologically active substances are diflubenzuron, cyromazine, diazinon, dichlorvos, chlorfenvinphos, fenchlorphos, prόpetamphos, coumaphos, carbophenthion, amitraz, rotenone, piperonyl butoxide, deltamethrin, cycloprothrin, cypermethrin, α-cypermethrin, cyhalothriri, bifenthrin, permethrin, phenothrin, flumethrin, cyfluthrin, cyphenothrin, tralomethrin, tralocythrin or 5 fenvalerate, magnesium fluorosilicate, abamectin, ivermectin, moxidectin, doramectin and diazinon. Formulations according to this invention may also include an antioxidant such as vitamin C, α-tocopherol and butylhydroxytoluene. A further embodiment of this invention provides a process for producing a o formulation for topical application to a wool producing animal, said process comprising mixing an active agent with a substance comprising at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. A still further embodiment of this invention provides a process for producing 5 a formulation for topical application to a wool producing animal, said process comprising mixing an active agent with a substance having substantially similar hydrophilic-lipophilic values and/or oxidation resistant properties to at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. Another embodiment of this invention provides a method for the treatment or prophylaxis of a wool producing animal, which method comprises the topical application of an effective amount of a formulation in accordance with the present invention. The skin irritancy problems which can arise when using conventional formulations, particularly when the active agent is a synthetic pyrethroid, are less likely to occur with the formulations of the present invention. This is because, they are able to allow the same biological effect to be achieved with a much smaller payload of active ingredient, and also because the wool grease component of the formulation decreases skin penetration by the active ingredient. It will be noted, also, that the invention makes use of materials which are eminently acceptable environmentally, particularly as the components of an animal's own secretions or analogues thereof may be used. Because of the present surprising discovery (arising from experimental work involving fractions of wool grease with a differing susceptibility to oxidation) of the connection between oxidation susceptibility and lack of diffusion over the skin of a wool producing animal, the inventors are confident that those fractions also having a substantially neutral oxidation profile as shown in Example 2 herein and those components, in particular the various predominant esters of wool grease also having a substantially neutral oxidative profile (including analogues and mixtures thereof) and substantially similar compounds are equally encompassed b the invention. Similarly it is to be understood that the formulations and methods of this invention are not to be limited to the use of sterol or wax esters obtained from wool grease, or to their synthetic analogues, but also embrace the use of such substances from other natural sources. The formulation of the invention may be liquid and would therefore normally be applied by plunge or spray dipping, by jetting with a hand held spray or in a race, or by a back-line spray or pour-on. Because the present invention facilitates the preparation of formulations thicker than conventional ones, and may be thixotropic or in the form of a paste, it offers the possibility of using a wider variety of application techniques than hitherto, such as the use of ribbed or spiked rollers to deposit the chemical at skin level, possibly as elements of races in which the rollers make contact with the back and sides of the animals to be treated or other applicators adapted to penetrate the fleece of the animal. Brief Description of the Drawings Figure 1 illustrates the thin layer chromatography profile of wool grease as conducted in Example 1. Figure 2 illustrates the oxidation of wool grease fractions with time after shearing. Figure 3 illustrates the circular 'map' of initial "spot" distribution studies conducted in Example 4. 5 Figure 4 illustrates the movement of deltamethrin in Clout-S, fraction 1 and fraction 5 into concentric rings at 1 , 4 and 7 days after application. Figure 5 illustrates the quantity of deltamethrin remaining at point of application and in skin swab 5 days after deltamethrin was applied as Clout-S and in fraction 1 and fraction 5 vehicles, o Figure 6 illustrates the in vivo trials. Concentration of deltamethrin in wool sampled near back-line application strip assessed after application as Clout-S and in fraction 1 and fraction 5 vehicles. Figure 7 illustrates the in vivo trials. Concentration of deltamethrin assessed in wool sampled at VΛ dorsal-ventral distance. 5 Figure 8 illustrates the in vivo trials. Concentration of deltamethrin assessed in wool sampled at % dorsal- ventral distance. Figure 9 illustrates the in vitro exposure of wool samples (collected from near back-line over 42 days after application of deltamethrin in Fraction 1 and Clout-S) to synthetic pyrethroid-resistant lice. 0 Figure 10 illustrates the in vitro exposure of wool samples (collected at' VA dorsal-ventral distance over 42 days after application of deltamethrin in Fraction 1 and Clout-S) to synthetic pyrethroid-resistant lice. Figure 11 illustrates the in vitro exposure of wool samples (collected at 3 Λ dorsal-ventral distance over 42 days after application of deltamethrin in Fraction 1 5 and Clout-S) to synthetic pyrethroid-resistant lice. Figure 12 illustrates the in vivo trials, of deltamethrin applied as Clout-S and in fraction 1 and fraction 5 vehicles. Total amount of deltamethrin remaining at point of application 98 days after application assessed. Figure 13 illustrates the autoradiograph of samples of wool collected from o back-line of sheep treated with deltamethrin as Clout-S and in fraction 1 and fraction 5 vehicles. Figure 14 illustrates the in vivo trials comparing deltamethrin in Clout-S and in a fraction 1 vehicle. Concentration of deltamethrin in wool sampled adjacent to the back-line assessed after application of deltamethrin in fraction 1 and Clout-S. 5 Figure 15 illustrates the in vivo trials comparing deltamethrin in Clout-S and in a fraction 1 vehicle. Concentration of deltamethrin in wool sampled at V* dorsal-ventral distance assessed after application of deltamethrin in fraction 1 and Clout-S. Figure 16 illustrates the in vivo trials comparing deltamethrin. in Clout-S and 0 in a fraction 1 vehicle. Concentration of deltamethrin in wool sampled at % dorsal-ventral distance assessed after application of deltamethrin in fraction 1 and Clout-S. Best Mode and Other Modes for Carrying Out the Invention The invention will now be described with reference to specific examples. It will be appreciated that the following examples illustrate only some of the many variables which are within the ambit of the invention. It will also be realised that quantities stated are, of necessity, approximate. Example 1 Wool grease was fractionated by silica gel chromatography into the following basic groups which were identified by thin layer chromatography against known reference standards. This is illustrated in figure 1 in which A represents the location of hydrocarbons (small amounts), sterol esters, eg. cholesterol palmitate, wax esters, eg. palmitic acid lauryl eater. B represents the location of triterpene esters containing substantially unoxidised isocholesterols. C represents the location of slightly oxidised sterol esters, wax esters and saturated fatty acids. D represents the location of free fatty acids, some free sterols, eg. lanosterol and highly oxidised esters. E represents the location of sterols, oxidised sterols, oxidised or polar lipids, peroxides and aldehydes. The following table sets out the legend for the x- axis of figure 1. 1 2 3 4 5 6 7 Fraction 1 Fraction 2 Fraction 3 Fraction 4 Fraction 5 Diglycerides Cholesterol 8 9 10 11 12 13 14 Lanosterol Palmitic Triglycerides Lauryl Cholesterol Squalene Wool Grease Acid palmitate stearate The major components of the fractions are set out below. Fraction 1 Sterol and wax esters; small amounts of hydrocarbons. Fraction 2 Triterpene esters containing substantially unoxidised isocholesterols. Fraction 3 Slightly oxidised wax and sterol esters, and more highly saturated fatty acids. Fraction 4 Free fatty acids, free sterols (cholesterol, lanosterol), and more highly oxidised esters. Fraction 5 Hydroxylated sterols, oxidised lipids containing peroxides and aldehydes, polar unsaturated compounds, free alcohols and hydroxy acids. Wool Grease Extractions Wool was clipped from insecticide-free and lice-free sheep, then extracted with petroleum spirit (BR 40-60°C) (Ajax Univar) containing 0.01 % butylhydroxy toluene. The wool was repeatedly extracted in all-glass beakers, to avoid contact with gloves or any plastic component. The extract was allowed to settle, then filtered through Whatman No.l filter paper, followed by rotary evaporation at 32-37 °C. The wax obtained was then further evaporated under vacuum in a desiccator containing silica gel until a constant weight was obtained. Column Fractionation Fractionation was performed on sintered glass columns (porosity No. 3). The 5 column dimensions were 34mm I.D. and 204mm in height (130mL capacity). Silica gel HF254 was used as the adsorbent. The column was fitted to a side arm flask connected to a vacuum pump and packed, then washed with at least one column volume petroleum spirit and with the solvent to top the wax was applied as a solution in petroleum spirit at an approximate concentration of 0.4-0.5g/mL. The wax components were eluted with petroleum spirit containing increasing amounts of diethyl ether (Ajax, Univar), then more polar solvents such as chloroform and methanol to elute very polar fractions. All solvents used contained 0.01 % butylhydroxytoluene. Elution profile s Packed column using 52g adsorbent, then applied 1.8g grease. One hundred mL fractions were collected. Elution Step Elution Vol. mL Solvent Sub-fraction 1 100 petroleum spirit 1 2 200 3% diethyl ether 2.1, 2.2 3 200 5% diethyl ether 3.1, 3.2 4 200 10% diethyl ether 4.1, 4.2 5 . 200 20% diethyl ether 5.1, 5.2 6 200 30% diethyl ether 6.1, 6.2 7 200 60% diethyl ether 7.1, 7.2 8 200 100% diethyl ether 8.1, 8.2 9 200 chlorofor /methanol 50:50 9.1, 9.2 All fractions were spotted on a silica gel G TLC plate and developed in a tank containing petroleum spirit:diethyl etheπacetic acid 90:10:1. Detection of the lipid fractions was achieved by spraying the plates with 0.2% 2',7'-dichlorofluorescein o in methanol or ethanol, then viewing under UV light (UVA and UVC). Fractions with similar RF values were combined to give 5 main fractions: Sub-fraction Appearance Fraction No. 2.1 to 3.1 waxy, translucent, clear, slightly runny 1 3.2 to 4.1 waxy, more solid than fraction 1, creamy 2 4.2 to 5.1 slightly yellow, more solid, fatty, oily 3 5.2 to 6.1 as for fraction 3 but more oily 4 6.2 to 9.2 yellow, brown, fatty, solidifies easily 5 This preparation was scaled up to a preparative scale using similar elution profile Formulation of Synthetic Pyrethroid in Fraction 1 and Fraction 5 Deltamethrin was dissolved in approximately 3mL equal parts acetone :petroleum spirit (40°-60° Univar) then thoroughly mixed with approximately 8g of fraction 1 or fraction 5. The acetone:petroleum spirit was 5 then removed by evaporation. The quantity of deltamethrin added to fraction 1 or fraction 5 carrier was adjusted to give a final concentration of lOmg deltamethrin/mL carrier. Example 2 To determine the rates of oxidation of the fractions under field conditions, o samples of wool grease were taken from animals at spaced intervals after shearing, and the oxidation levels of the fractions were measured by the method of Asakawa et al (12). The fraction 1 sample of Example 1 was found to have oxidised to 0.03 units 3 days after secretion, and the oxidation had increased to only 0.2 units by 140 days; whereas the oxidation of a fraction 5 sample of Example 1 was 2.8 units s and 7.6 units after 3 and 140 days respectively (one unit of oxidation is equivalent to lnmole malondialdehyde/50mg sample). Example 3 Figure 2 depicts a rate of oxidation of each of fractions 1 to 5. Under field conditions samples of wool grease were taken from animals at spaced intervals 0 after shearing from 3 to 21 days and the oxidation levels of the fractions were measured by the method of Asakawa et al (12). Fractions 1 and 2 in particular remain relatively unoxidised over the time studied. Fraction 3 showed slight oxidation over the time while fraction 4 and fraction 5 were relatively highly oxidised with fraction 5 being the most oxidised fraction. 5 Example 4 Three 10mm diameter spots of [ 14 C]-deltamethrin were applied 25cm apart to the backs of each of eight freshly shorn sheep, either as Clout-S (a commercially available aqueous preparation produced by Pitman-Moore for the topical treatment of sheep lice) or dissolved in a solution of fractions 1 or 5 of wool grease prepared o according to the method of Example 1 above. Outside a 5mm wide buffer zone around each applied spot, concentric 20mm wide rings (Figure 3) of wool and skin grease were collected from the sheep on days 1, 4 and 7 after shearing. The total amount of deltamethrin in each annulus was determined by liquid scintillation spectrometry. The integrity of the extracted [ 14 C] as deltamethrin was confirmed 5 in random samples using high performance liquid chromatography. When the deltamethrin was applied as the commercial formulation, Clout-S, there was only limited diffusion, the greater part of the dose remaining within the application spot. When the deltamethrin was applied in fraction 5 of wool grease, (the most oxidised fraction) diffusion was similar to that of Clout-S, and the greater part of deltamethrin still remained at the application site. However, enhanced diffusion of deltamethrin was clearly demonstrated when deltamethrin was applied in the minimally oxidised fraction 1. By day 7 the quantity of deltamethrin diffusing to annulus 4 was equivalent to, or greater than, the quantity which had diffused only to annulus 1 when applied in Clout-S or fraction 5. Figure 4 depicts the results of the amount of deltamethrin in Clout-S, fraction 1 and fraction 5 in each annulus 1 , 4 and 7 days after shearing, Figure 5 depicts the amount of deltamethrin remaining at the point of application in wool and on skin of the sheep five days after application of deltamethrin in each of Clout-S, fraction 1 and fraction 5. When the applied spot was removed by clipping the wool at skin level after days 1, 4 and 7, over 95% of the applied dose of Clout-S and fraction 5 5 formulations was retained in this wool sample. When administered in fraction 1, as little as 74% of the deltamethrin remained after 7 days, indicating a significantly greater diffusion from the application site. (Table 1). Analyses of skin lipid swabs from the site of application, after removal of wool containing applied formulations, showed that by day 7 less deltamethrin was associated with skin lipids when applied as Clout-S or in fraction 5 than when ' applied in fraction 1 (Table 2). That is, there was an enhanced distribution of deltamethrin towards the skin surface, where it would be most likely to be effective in control of lice and other skin residing pests. Table 1 5 % Deltamethrin Remaining on Wool at Centre Day Clout-S Fraction 1 Fraction 5 1 97.3 74.8 97.0 4 98.8 67.9 97.1 7 97.9 74.0 93.0 Table 2 % Deltamethrin Remaining in Skin Grease Day Clout-S Fraction 1 Fraction 5 1 2.7 10.1 9.3 4 0.6 3.9 3.5 7 0.04 2.8 0.9 It is clear that less deltamethrin remains on the wool at the point of application when in fraction 1 than in fraction 5 or Clout-S. Of the deltamethrin o remaining at the point of application, a higher portion of deltamethrin is in the skin grease when applied in fraction 1 in contrast to the deltamethrin in Clout-S or fraction 5. Example 5 A 30cm x 1cm line of [ C]-deltamethrin was applied along the dorsal mid- line ("back-line") of replicate merino sheep within two to three hours after shearing, either as Clout-S (in six sheep) or dissolved in solutions of each of 5 fraction 1 (in five sheep) or fraction 5 (in three sheep). Wool samples were collected from the sheep at spaced time intervals after application over a period of 100 days. Figure 6 depicts the quantities of deltamethrin in wool grease extracted from wool samples taken adjacent (within 50mm) of the back-line at spaced intervals over 100 days. A higher diffused concentration of deltamethrin in fraction 1 can be noted especially from 20 days on in contrast to low levels of deltamethrin in fraction 5 and Clout-S, clearly indicating a poorer spread over the period of deltamethrin from the back-line when applied in fraction 5 and Clout-S rather than in fraction 1. s Figure 7 depicts the quantities of deltamethrin in wool grease extracted from wool taken from a meridian X A of the dorsal-ventral distance from the back-line of the sheep. Again a higher concentration of deltamethrin over the 100 day period when applied in fraction 1 can be noted when compared with the concentrations of deltamethrin in fraction 5 and Clout-S. 0 Figure 8 depicts the quantities of deltamethrin in wool grease extracted from wool samples taken from a meridian 3 λ of the dorsal-ventral distance from the back-line of the sheep. Once again the concentration of deltamethrin over the 100 day period when applied in fraction 1 is higher than that in fraction 5 and Clout-S. Example 6 5 As in Example 5 a 30cm x 1cm line of deltamethrin was applied along the back-line of sheep within two to three hours from shearing either as Clout-S or dissolved in a solution of fraction 1. Wool samples were collected from replicate sheep at spaced intervals after application over a period of 42 days and the samples then exposed in vitro to pyrethroid-resistant lice. The percentage of viable lice o remaining in each sample of wool was determined after 24 hours exposure of the wool to lice. Figure 9 depicts the percentage of viable lice following in vitro exposure to lice of samples of wool taken adjacent (within 50mm) of the back-line at 1, 4, 8, 14, 21, 28 and 42 days after deltamethrin was applied. 5 Figure 10 depicts the percentage of viable lice following in vitro exposure to lice of samples of wool taken from a meridian VΛ of the dorsal-ventral distance from the back-line of the sheep at 1, 4, 8, 14, 21, 28 and 42 days after deltamethrin was applied. It is clear from each of figures 9 and 10 that the insecticidal properties of wool from sheep treated with deltamethrin in fraction 1 is consistently higher over the 42 day period than the sheep treated with Clout-S due to the greater concentration/availability of deltamethrin in the wool of the sheep treated with 5 fraction 1 than in the wool of the sheep treated with Clout-S. Figure 11 depicts the percentage of viable lice following in vitro exposure to lice of samples of wool taken from a meridian % of the dorsal-ventral distance from the back-line of the sheep at 1, 4, 8, 14, 21, 28 and 42 days after deltamethrin was applied. It is clear from figure 11 that even at this distance of o sampling from the mid-line application of deltamethrin, the fraction 1 containing deltamethrin is more efficacious than Clout-S. Example 7 Again as described in Example 5 a 30cm x 1cm line of [ 14 C]-deltamethrin was applied along the back-line of freshly shorn Merino sheep either as Clout-S or 5 dissolved in solutions of each of fraction 1 or fraction 5. Wool grease was extracted from all of the wool in the back-line application strip collected 98 days after application and the total amount of [ C]-deltamethrin remaining as a percentage of the amount initially applied was determined. The results are depicted in Figure 12. In sheep treated with both deltamethrin in fraction 5 and o Clout-S, 95% or more deltamethrin remained at the application point. Only about 66% of the fraction 1 -applied deltamethrin remained in the application strip indicating that about 33 % of the fraction 1 -applied deltamethrin had diffused away from the application point. Example 8 5 Again as in Example 5 a 30cm x 1cm line of [ 14 C] deltamethrin was applied along the back-line of freshly shorn sheep either as Clout-S or dissolved in a solution of each of fraction 1 and fraction 5. Wool samples were taken from the back-line of replicate sheep 98 days after application of deltamethrin and placed on an x-ray plate for an autoradiograph. o Figure 13 depicts the position of [ 14 C] deltamethrin in relation to the whole wool staple length. In sample 429, being wool containing Clout-S, and in sample 673, being wool containing the fraction 5 applied deltamethrin, the deltamethrin activity is at the top of the wool which is the region of the length of the wool which remains on the sheep when the deltamethrin was applied following shearing. 5 Clearly when in the form of Clout-S or when dissolved in fraction 5 the deltamethrin associates with the existing wool grease and stays as a discrete band in the wool. In contrast sample 675, being wool containing the fraction 1 -applied deltamethrin, the deltamethrin presence is indicated by a distinct shadow down the wool staple over at least a further 1 to 1.5cm clearly indicating that deltamethrin in the fraction 1 vehicle continues to exchange with freshly secreted wool grease for several months after application resulting in the presence of greater amounts of deltamethrin down towards the skin where lice and other ectoparasites dwell. 5 Example 9 The trials conducted in Example 5 were repeated in further sheep except that the deltamethrin was applied either as Clout-S (in three sheep) or dissolved in a solution of fraction 1 (in three sheep). The wool samples were collected at spaced intervals after application over a period of 42 rather than 100 days. o Figure 14 depicts the quantities of deltamethrin in wool grease extracted from wool samples taken adjacent (within 50mm) of the back-line over the period and indicates that between 8 and 28 days, and to a lesser extent after 28 days, a higher diffuse concentration of deltamethrin was obtained in samples taken from the fraction 1 -deltamethrin treated sheep than in samples taken from sheep treated with s Clout-S. Figures 15 and 16 depict the quantities of deltamethrin in wool grease extracted from meridians l A and % respectively of the dorsal-ventral distance from the back-line. Again a higher concentration of deltamethrin over the 42 day period can be noted in the samples taken from the fraction 1 -deltamethrin treated sheep o than from those sheep treated with Clout-S. References 1. Truter, E.V. Wool Wax Chemistry and Technology. Cleaver-Hume Press Ltd 1, London 1956. 2. J. L. Hoare. Wool Research Organisation Report. The Recovery and 5 Characterization of Wool Grease. In New Zealand, 1976. 3. Christie. W.W. Lipid Analysis. Isolation, Separation, Identification and Structural Analysis of Lipids. Pergamon Press, 1982. 4. Downing, D.T., Kranz, Z.H. and Murray, K.E. Studies in Waxes. Australian Journal of Chemistry, 13, 80, 1960. 0 5 (A) Fawaz, F., Chaigneau, M. and Puisieux, F. Ann. Pharm. Franc. 32(3), 215, 1974. (B) Fawaz, F., Chaigneau, M. and Puisieux, F. Ibid 32(5), 301, 1974. (C) Fawaz, F., Chaigneau, M. and Puisieux, F. Ibid 31 , 217, 1973. (D) Fawaz, F., Miet, C. and Puisieux, F. Ibid 32, 59, 1974. 6. Motiuk, K. Wool Wax Alcohols: A Review and Wool Wax Acids: A 5 Review. J. Am. Oil Chem. Soc, 56, 1979 (SD&C Technical), 651-658 and 91-97. 7. Downing, D.T., Strauss, J.S., Ramasastry, P., Abel, M., Lee, C.W. and Pochi, P. E. The Journal of Investigative Dermatology, 64, 215-219, 1975. 8. Lamparczyk, H. and Miszkiel, M. Gas Chromatographic Evaluation of Wool Alcohols supported by Principal Component Analysis. Chromatographia, 31 No.(5/6), 1991. 9. Crabtree, H.E. and Truter, E.V. Constitution of some Steroid Esters of s Wool Wax. J. Sci. Food Agric, 25, 1441-1449, 1974. 10. Nicolaides, N., Fu, H.C. and Ansari, M.N.A. Diester Waxes in Surface Lipids of Animal Skin. Lipids, 5 No. 3, 299, 1969. 11. Kolattukudy, P.E. Chemistry and Biochemistry of Natural Waxes. Elsevier (edited by P.E. Kolattukudy), 1-48, 1976. o 12. Asakawa, T and Matsushita, S. Thiobarbituric Acid Test for Detecting Lipid Peroxides, Lipids, Vol 14, No 4, 1979 Industrial Applicability The formulation of the invention can readily be utilised for the treatment or prophylaxis of a condition or disease in an animal.

Claims: Claims 1. A wool grease fraction having a substantially neutral oxidation profile. 2. The fraction as claimed in claim 1, wherein said fraction substantially comprises sterol esters and wax esters. 3. The fraction as claimed in claim 1, wherein said fraction substantially comprises triterpene esters containing substantially unoxidised isocholesterols. 4. A formulation for topical application to wool producing animal, said formulation comprising a light stable active agent in a vehicle comprising a wool grease fraction having a substantially neutral oxidation profile, 5. A formulation as claimed in claim 4, wherein said fraction substantially comprises sterol esters and wax esters. 6. A formulation as claimed in claim 4, wherein said fraction substantially comprises triterpene esters containing substantially unoxidised isocholesterols. 7. A formulation for topical application to wool producing animal, said formulation comprising a light stable active agent in a vehicle comprising at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. 8. The formulation as claimed in claim 7, wherein said sterol ester is of a sterol and a long chain fatty acid. 9. The formulation as claimed in claim 8, wherein said sterol comprises at least one of a cholesterol, triterpene alcohol, lanosterol, dihydrolanosterol or isocholesterol. 10. The formulation as claimed in any one of claims 7 to 9, wherein said wax ester is of a long chain water insoluble alcohol and a long chain fatty acid. 11. The formulation as claimed in claim 10, wherein said alcohol contains from 14 to 36 carbon atoms. 12. The formulation as claimed in any one of claims 8 to 11 , wherein said fatty acid contains from 7 to 36 carbon atoms. 13. The formulation as claimed in any one of claims 7 to 12, wherein said sterol ester comprises at least one of cholesteryl palmitate or cholesteryl stearate. 14. The formulation as claimed in any one of claims 7 to 12, wherein said wax ester comprises at least one of palmitic acid lauryl ester or stearic acid lauryl ester. 15. The formulation as claimed in any one of claims 7 to 12, wherein said sterol ester or said wax ester is a monoester or a diester. 16. The formulation as claimed in any one of claims 4 to 15, further comprising a hydrocarbon. 17. The formulation as claimed in any one of claims 4 to 16, further comprising an antioxidant. 18. The formulation as claimed in claim 17, wherein said antioxidant is at least one of vitamin C, α-tocopherol or butylhydroxy toluene. 19. A formulation for topical application to an animal, said formulation comprising a substance having substantially similar hydrophilic-lipophilic values 5 and/or oxidation resistant properties to at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. 20. A formulation as claimed in any one of claims 4 to 19, together with at least one of an acceptable carrier, diluent, excipient or adjuvant. o 21. The formulation as claimed in any one of claims 4 to 20, wherein said active agent is a pesticide. 22. The formulation as claimed in claim 21, wherein said pesticide is at least one of an acaricide, an antibiotic, a fungicide, an insecticide, an anthelmintic agent, an insect growth regulator, an anti-viral agent, an attractant, a wound s protectant or a repellent. 23. The formulation as claimed in claim 21 , wherein said pesticide is at least one of a pyrethroid or an organophosphate. 24. The formulation as claimed in claim 23, wherein said pyrethroid is at least one of deltamethrin, cycloprothrin, cypermethrin, α-cypermethrin, o cyhalothrin, bifenthrin, permethrin, phenothrin, flumethrin, cyfluthrin, cyphenothrin, tralomethrin, tralocythrin or fenvalerate. 25. The formulation as claimed in claim 23 or claim 24, wherein said organophosphate is diazinon. 26. The formulation as claimed in any one of claims 22 to 25, wherein said 5 insect growth regulator is at least one of cyromazine, a benzoyl urea or a triazine. 27. The formulation as claimed in any one of claims 21 to 26, wherein said pesticide is at least one of abamectin, ivermectin, moxidectin or doramectin. 28. The formulation as claimed in any one of claims 21 to 27, wherein the ratio of said pesticide to said ester is from 1:20 to 1:200. 0 29. A formulation for topical application to a wool producing animal, said formulation being substantially as hereinbefore described with reference to any one of the examples but excluding the comparative examples. 30. A process for producing a formulation for topical application to a wool producing animal, said process comprising mixing an active agent with the fraction 5 of any one of claims 1 to 3. 31. A process for producing a formulation for topical application to a wool producing animal, said process comprising mixing an active agent with a substance comprising at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. 32. A process for producing a formulation for topical application to a wool producing animal, said process comprising mixing an active agent with a substance having substantially similar hydrophilic-lipophilic values and/or oxidation resistant properties to at least one of a sterol ester, a wax ester, a triterpene ester containing 5 substantially unoxidised isocholesterols or an analogue thereof. 33. A process for producing a formulation for topical application to a wool producing animal, said process being substantially as hereinbefore described with reference to any one of the examples. 34. A formulation for topical application to a wool producing animal o produced by the process of any one of claims 30 to 33. 35. A method for the treatment or prophylaxis of a condition, infestation or disease in a wool producing animal requiring said treatment or prophylaxis which method comprises topically applying to said animal an effective amount of a formulation as claimed in any one of claims 4 to 29 or 34. s 36. The method as claimed in claim 35, wherein said condition, infestation or disease can be induced by an ectoparasite. 37. The method as claimed in claim 36, wherein said ectoparasite is at least one of a blowfly, lice, itch mite or scab. 38. The method as claimed in any one of claims 35 to 37, wherein said 0 animal is a sheep. 39. The method as claimed in any one of claims 35 to 37, wherein said animal is a llama, alpaca, goat or rabbit. 40. The method as claimed in any one of claims 35 to 39, wherein said formulation is a liquid. 5 41. The method as claimed in any one of claims 35 to 40, wherein said formulation is applied as a continuous spray. 42. The method as claimed in any one of claims 35 to 41, wherein said formulation is a paste or is a thixotropic agent. 43. The method as claimed in any one of claims 35 to 42, wherein said o formulation is applied by means of at least one line along the back, side or over a flank of said animal. 44. The method as claimed in any one of claims 35 to 43, wherein said formulation is applied with an applicator adapted to penetrate the wool of said animal. 5 45. The method as claimed in claim 44, wherein said applicator is a ribbed or a spiked roller, a comb or other hand or mechanically operated applicator. AMENDED CLAIMS [received by the International Bureau on 16 August 1995 ( 16.08.95) ; original cl aims 1 + 20 amended ; remaining claims unchanged (3 pages ) ] I . A carrier for topical formulation of useful active ingredients in human and veterinary applications, comprising a wool grease fraction having a substantially neutral oxidation profile. 2. The fraction as claimed in claim 1, wherein said fraction substantially comprises sterol esters and wax esters. 3. The fraction as claimed in claim 1, wherein said fraction substantially comprises triterpene esters containing substantially unoxidised isocholesterols. 4. A formulation for topical application to wool producing animal, said formulation comprising a light stable active agent in a vehicle comprising a wool grease fraction having a substantially neutral oxidation profile. 5. A formulation as claimed in claim 4, wherein said fraction substantially comprises sterol esters and wax esters. 6. A formulation as claimed in claim 4, wherein said fraction substantially comprises triterpene esters containing substantially unoxidised isocholesterols. 7. A formulation for topical application to wool producing animal, said formulation comprising a light stable active agent in a vehicle comprising at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. 8. The formulation as claimed in claim 7, wherein said sterol ester is of a sterol and a long chain fatty acid. 9. The formulation as claimed in claim 8, wherein said sterol comprises at least one of a cholesterol, triterpene alcohol, lanosterol, dihydrolanosterol or isocholesterol. 10. The formulation as claimed in any one of claims 7 to 9, wherein said wax ester is of a long chain water insoluble alcohol and a long chain fatty acid. I I . The formulation as claimed in claim 10, wherein said alcohol contains from 14 to 36 carbon atoms. 12. The formulation as claimed in any one of claims 8 to 11, wherein said fatty acid contains from 7 to 36 carbon atoms. 13. The formulation as claimed in any one of claims 7 to 12, wherein said sterol ester comprises at least one of cholesteryl palmitate or cholesteryl stearate. 14. The formulation as claimed in any one of claims 7 to 12, wherein said wax ester comprises at least one of palmitic acid lauryl ester or stearic acid lauryl ester. 15. The formulation as claimed in any one of claims 7 to 12, wherein said sterol ester or said wax ester is a monoester or a diester. 16. The formulation as claimed in any one of claims 4 to 15, further comprising a hydrocarbon. 17. The formulation as claimed in any one of claims 4 to 16, further comprising an antioxidant. 18. The formulation as claimed in claim 17, wherein said antioxidant is at least one of vitamin C, α-tocopherol or butylhydroxy toluene. 19. A formulation for topical application to an animal, said formulation comprising a substance having substantially similar hydrophilic-lipophilic values and/or oxidation resistant properties to at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. 20. A formulation as claimed in any one of claims 4 to 19, together with at least one of an acceptable further carrier, diluent, excipient or adjuvant. 21. The formulation as claimed in any one of claims 4 to 20, wherein said active agent is a pesticide. 22. The formulation as claimed in claim 21 , wherein said pesticide is at least one of an acaricide, an antibiotic, a fungicide, an insecticide, an anthelmintic agent, an insect growth regulator, an anti-viral agent, an attractant, a wound protectant or a repellent. 23. The formulation as claimed in claim 21 , wherein said pesticide is at least one of a pyrethroid or an organophosphate. 24. The formulation as claimed in claim 23, wherein said pyrethroid is at least one of deltamethrin, cycloprothrin, cypermethrin, α-cypermethrin, cyhalothrin, bifenthrin, permethrin, phenothrin, flumethrin, cyfluthrin, cyphenothrin, tralomethrin, tralocythrin or fenvalerate. 25. The formulation as claimed in claim 23 or claim 24, wherein said organophosphate is diazinon. 26. The formulation as claimed in any one of claims 22 to 25, wherein said insect growth regulator is at least one of cyromazine, a benzoyl urea or a triazine. 27. The formulation as claimed in any one of claims 21 to 26, wherein said pesticide is at least one of abamectin, ivermectin, moxidectin or doramectin. 28. The formulation as claimed in any one of claims 21 to 27, wherein the ratio of said pesticide to said ester is from 1 :20 to 1:200. 29. A formulation for topical application to a wool producing animal, said formulation being substantially as hereinbefore described with reference to any one of the examples but excluding the comparative examples. 30. A process for producing a formulation for topical application to a wool producing animal, said process comprising mixing an active agent with the fraction of any one of claims 1 to 3. 31. A process for producing a formulation for topical application to a wool producing animal, said process comprising mixing an active agent with a substance comprising at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. 32. A process for producing a formulation for topical application to a wool producing animal, said process comprising mixing an active agent with a substance 5 having substantially similar hydrophilic-lipophilic values and/or oxidation resistant properties to at least one of a sterol ester, a wax ester, a triterpene ester containing substantially unoxidised isocholesterols or an analogue thereof. 33. A process for producing a formulation for topical application to a wool producing animal, said process being substantially as hereinbefore described with o reference to any one of the examples. 34. A formulation for topical application to a wool producing animal produced by the process of any one of claims 30 to 33. 35. A method for the treatment or prophylaxis of a condition, infestation or disease in a wool producing animal requiring said treatment or prophylaxis which 5 method comprises topically applying to said animal an effective amount of a formulation as claimed in any one of claims 4 to 29 or 34. 36. The method as claimed in claim 35, wherein said condition, infestation or disease can be induced by an ectoparasite. 37. The method as claimed in claim 36, wherein said ectoparasite is at least o one of a blowfly, lice, itch mite or scab. 38. The method as claimed in any one of claims 35 to 37, wherein said animal is a sheep. 39. The method as claimed in any one of claims 35 to 37, wherein said animal is a llama, alpaca, goat or rabbit. 5 40. The method as claimed in any one of claims 35 to 39, wherein said formulation is a liquid. 41. The method as claimed in any one of claims 35 to 40, wherein said formulation is applied as a continuous spray. 42. The method as claimed in any one of claims 35 to 41, wherein said 0 formulation is a paste or is a thixotropic agent. 43. The method as claimed in any one of claims 35 to 42, wherein said formulation is applied by means of at least one line along the back, side or over a flank of said animal. 44. The method as claimed in any one of claims 35 to 43, wherein said 5 formulation is applied with an applicator adapted to penetrate the wool of said animal. 45. The method as claimed in claim 44, wherein said applicator is a ribbed or a spiked roller, a comb or other hand or mechanically operated applicator. STATEMENT UNDER ARTICLE 19 Claims 1 and 20 have been amended. The remaining claims are unchanged. Claims as amended are both novel and comprise an inventive step given all of the prior art referred to in the international search report, on the following basis. 1. AU,B,21947/83 describes a pour-on formulation for the control of ectoparasites, particularly for use on Merino sheep, said formulation comprising pyrethroids. It does not describe a wool grease fraction with a substantially neutral oxidation profile, nor the use of such a fraction as a vehicle for the delivery of pharmaceuticals. 2. AU,A,26320/88 describes a method of killing and/or repelling lice or preventing lice feeding and/or oviposition by mixing the extracts from the seeds or kernels of meliaceous plants, particularly the neem tree, with an inert carrier and applying the mixture to the fleece, skin or coat of an animal. However, this invention does not describe the use of a wool grease fraction with a substantially neutral oxidation profile, nor the use of such a fraction as a vehicle for the delivery of pharmaceuticals. 3. The documents: Cosmetics and Toiletries Volume 105 (1990) page 108, Grant and Hackh's Chemical Dictionary 5th Edition (Grant, R et al) McGraw-Hill (1987) page 330 and The Merck Index 11th Edn. Merck & Co. Inc. (1989) Monograph No. 5231 page 845, all refer to the compound lanolin or its constituents, a fat like secretion of the sebaceous glands of sheep, which is deposited onto the wool fibres, containing a complex mixture of esters, polyesters of high weight alcohols and fatty acids. It does not describe a wool grease fraction with a substantially neutral oxidation profile, nor the use of such a fraction as a vehicle for delivery of pharmaceuticals. 4. Derwent WPAT Online Abstract Accession No. 93-172616, JP,A,05105612 (KURODA JAPAN KK) describes an external agent for skin, such as cosmetics, quasi drug, or medicine blended with an ester of a lanolin fatty acid and a 12 to 22 carbon saturated or straight chain alcohol. The objective of the invention is to give an improved external agent for skin, which provides for example, excellent combing properties, softness, luster, setting properties etc. It does not describe the use of a wool fraction with a substantially neutral oxidation profile, nor the use of such a fraction as a vehicle for biologically active agents. 5. Derwent WPAT Online Abstract Accession No. 78-42812A, JP,A,53049002 (TOYOBO KK) describes the saponification of a wool grease by the use of an alkaline catalyst into a wood alcohol. The objective of the invention is a method for separating isocholesterol and cholesterol from wood alcohol by the use of isopropyl alcohol and lower fatty acids. The method of separating wool grease components described by the applicant is superior to that described in this prior art reference. Also this prior art reference makes no mention of a wool grease fraction with a substantially neutral oxidation profile, nor the use of such a fraction as a vehicle for biologically active agents. 6. The documents: Textile Research Journal Volume 58 (1988) (Leaver, I.H. et al) pages 593-600 and Journal of the Textile Institute Volume 65 (1974) (McCracken, J.R. et al) pages 261-270 describe methods for the fractionation of wool grease. However, the method of separating wool grease fractions described by the applicant is superior to that described in these prior art references. Also this document is not an enabling reference for the use of a wool grease fraction as a vehicle for delivery of pharmaceuticals.

Inventors: DARWISH ALAN, HENNESSY DESMOND RONALD, MAXWELL COLIN ARTHUR, RUSSELL IAN MAXWELL, DARWISH, ALAN, HENNESSY, DESMOND, RONALD, MAXWELL, COLIN, ARTHUR, RUSSELL, IAN, MAXWELL
Applicants: AUSTRALIAN WOOL RESEARCH & PRO, COMMW SCIENT IND RES ORG, DARWISH ALAN, HENNESSY DESMOND RONALD, MAXWELL COLIN ARTHUR, RUSSELL IAN MAXWELL, AUSTRALIAN WOOL RESEARCH & PROMOTION ORGANISATION, COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH OR, DARWISH, ALAN, HENNESSY, DESMOND, RONALD, MAXWELL, COLIN, ARTHUR, RUSSELL, IAN, MAXWELL
Application year: 1995
Main classification: A61K47
IPC codes: A01N25, A61K9, A61K47, C11B11