EP0749324A1 - Formulation veterinaire - Google Patents

Formulation veterinaire

Info

Publication number
EP0749324A1
EP0749324A1 EP95912077A EP95912077A EP0749324A1 EP 0749324 A1 EP0749324 A1 EP 0749324A1 EP 95912077 A EP95912077 A EP 95912077A EP 95912077 A EP95912077 A EP 95912077A EP 0749324 A1 EP0749324 A1 EP 0749324A1
Authority
EP
European Patent Office
Prior art keywords
formulation
wool
fraction
ester
animal
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP95912077A
Other languages
German (de)
English (en)
Other versions
EP0749324A4 (fr
Inventor
Desmond Ronald Hennessy
Alan Darwish
Colin Arthur Maxwell
Ian Maxwell Russell
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Commonwealth Scientific and Industrial Research Organization CSIRO
Australian Wool Research and Promotion Organization AWRAP
Original Assignee
Commonwealth Scientific and Industrial Research Organization CSIRO
Australian Wool Research and Promotion Organization AWRAP
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Commonwealth Scientific and Industrial Research Organization CSIRO, Australian Wool Research and Promotion Organization AWRAP filed Critical Commonwealth Scientific and Industrial Research Organization CSIRO
Publication of EP0749324A1 publication Critical patent/EP0749324A1/fr
Publication of EP0749324A4 publication Critical patent/EP0749324A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • A61K9/0017Non-human animal skin, e.g. pour-on, spot-on
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/02Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11BPRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
    • C11B11/00Recovery or refining of other fatty substances, e.g. lanolin or waxes
    • C11B11/005Lanolin; Woolfat

Definitions

  • 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.
  • Ectoparasites such as blowfly, lice, itch mite and scab, can seriously affect productivity in the sheep and cattle industries.
  • ectoparasites are controlled by the topical application of pesticides o such as organophosphates and synthetic pyrethroids.
  • pesticides such as organophosphates and synthetic pyrethroids.
  • 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
  • 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.
  • 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.
  • Alcohols consist of cholesterol and triterpene alcohols, aliphatic mono alcohols and alkane-l,2-diols. 5 Sterols and triterpene alcohols
  • 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 C ⁇ -C 35 .
  • the major components are C 2 ⁇ , 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
  • 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 C ⁇ 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 ⁇ and C 23 . 0 Wool Grease Acids
  • Wool grease acids consist predominantly of alkanoic, ⁇ -hydroxy and ⁇ - 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 , C ⁇ 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 C ⁇ , 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 , C ⁇ 9 , C 2 ⁇ , C 25 and C 27 .
  • Monoester grease are chiefly of two types (a) fatty acid esters of fatty alcohols and (b) fatty acid esters of sterols.
  • 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.
  • the alcoholic component of diesters of ⁇ -hydroxy acids do not include sterols, they are exclusively long-chain alcohols.
  • ⁇ 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).
  • Cholesterol forms at least 21 esters and is esterified almost entirely by iso and anteiso acids particularly in the ranges C 19 -C 2 ⁇ 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.
  • “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;
  • Steprol ester when used in this specification means a compound such as, but not limited to, cholesteryl palmitate or cholesteryl stearate;
  • Steprol when used in this specification means a compound such as, but not limited to, cholesterol, triterpene alcohol, lanosterol or dihydrolanosterol; and
  • Wood 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 invention provides a wool grease fraction having a substantially neutral oxidation profile.
  • 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.
  • the invention provides formulation for topical application to a wool producing animal, said formulation comprising a light stable ⁇ 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.
  • 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.
  • sterol esters 3o typically about 70%
  • wax esters typically about 25%
  • 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
  • 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.
  • biologically active agents which are solid or crystalline materials.
  • 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.
  • insect growth regulators which may be used include cyromazine, benzoyl ureas and triazines.
  • suitable biologically active substances are diflubenzuron, cyromazine, diazinon, dichlorvos, chlorfenvinphos, fenchlorphos, pr ⁇ petamphos, coumaphos, carbophenthion, amitraz, rotenone, piperonyl butoxide, deltamethrin, cycloprothrin, cypermethrin, ⁇ -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, ⁇ -tocopherol and butylhydroxytoluene.
  • an antioxidant such as vitamin C, ⁇ -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 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.
  • 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.
  • 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.
  • 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
  • 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 V ⁇ 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.
  • 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 ⁇ 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.
  • 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.
  • Fraction 3 Slightly oxidised wax and sterol esters, and more highly saturated fatty acids.
  • 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.
  • 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.
  • Figure 2 depicts a rate of oxidation of each of fractions 1 to 5.
  • 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
  • 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.
  • 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.
  • FIG. 8 depicts the quantities of deltamethrin in wool grease extracted from wool samples taken from a meridian 3 ⁇ of the dorsal-ventral distance from the back-line of the sheep.
  • 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.
  • Figure 10 depicts the percentage of viable lice following in vitro exposure to lice of samples of wool taken from a meridian V ⁇ 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
  • 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.
  • 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
  • the deltamethrin associates with the existing wool grease and stays as a discrete band in the wool.
  • 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.
  • Example 5 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.
  • 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.
  • the formulation of the invention can readily be utilised for the treatment or prophylaxis of a condition or disease in an animal.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Wood Science & Technology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Zoology (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Toxicology (AREA)
  • Dentistry (AREA)
  • Environmental Sciences (AREA)
  • Medicinal Preparation (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)

Abstract

Fraction de suint possédant un profil d'oxydation sensiblement neutre et formulation destinée à une application topique sur des animaux producteurs de laine, cette formulation comprenant un agent actif stable à la lumière dans un véhicule comprenant une fraction de suint possédant un profil d'oxydation sensiblement neutre. Formulation destinée à une application topique sur des animaux producteurs de laine, comprenant un agent actif stable à la lumière dans un véhicule comprenant au moins un ester parmi l'ester de stérol, l'ester de paraffine et l'ester de triterpène contenant des isocholestérols sensiblement non oxydés, ou un analogue de celui-ci. Procédés de fabrication de ces fractions et formulations, et méthodes de lutte contre les parasites à l'aide desdites formulations.
EP95912077A 1994-03-11 1995-03-10 Formulation veterinaire Withdrawn EP0749324A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AUPM4371/94 1994-03-11
AUPM4371A AUPM437194A0 (en) 1994-03-11 1994-03-11 Pesticide formulation
PCT/AU1995/000125 WO1995024219A1 (fr) 1994-03-11 1995-03-10 Formulation veterinaire

Publications (2)

Publication Number Publication Date
EP0749324A1 true EP0749324A1 (fr) 1996-12-27
EP0749324A4 EP0749324A4 (fr) 1997-09-17

Family

ID=3778987

Family Applications (1)

Application Number Title Priority Date Filing Date
EP95912077A Withdrawn EP0749324A4 (fr) 1994-03-11 1995-03-10 Formulation veterinaire

Country Status (7)

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EP (1) EP0749324A4 (fr)
AU (1) AUPM437194A0 (fr)
BR (1) BR9507059A (fr)
CA (1) CA2184994A1 (fr)
NZ (1) NZ282335A (fr)
WO (1) WO1995024219A1 (fr)
ZA (1) ZA952017B (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW524667B (en) 1996-12-05 2003-03-21 Pfizer Parasiticidal pyrazoles
US7514464B2 (en) 2003-12-18 2009-04-07 Pfizer Limited Substituted arylpyrazoles
GB0329314D0 (en) 2003-12-18 2004-01-21 Pfizer Ltd Substituted arylpyrazoles
GB201222820D0 (en) * 2012-12-18 2013-01-30 Croda Int Plc Woolscouring method and composition

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU539105B2 (en) * 1981-10-30 1984-09-13 Wellcome Australia Limited Pour-on formulation for the control of lice
AU2632088A (en) * 1987-11-30 1989-06-01 University Of Queensland, The Improvements in the inhibition of lice

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
No further relevant documents disclosed *
See also references of WO9524219A1 *

Also Published As

Publication number Publication date
EP0749324A4 (fr) 1997-09-17
BR9507059A (pt) 1997-09-02
WO1995024219A1 (fr) 1995-09-14
ZA952017B (en) 1995-12-11
AUPM437194A0 (en) 1994-03-31
CA2184994A1 (fr) 1995-09-14
NZ282335A (en) 1998-07-28

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