WO2007053902A1 - Méthode pour traiter des parasites - Google Patents

Méthode pour traiter des parasites Download PDF

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Publication number
WO2007053902A1
WO2007053902A1 PCT/AU2006/001685 AU2006001685W WO2007053902A1 WO 2007053902 A1 WO2007053902 A1 WO 2007053902A1 AU 2006001685 W AU2006001685 W AU 2006001685W WO 2007053902 A1 WO2007053902 A1 WO 2007053902A1
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WO
WIPO (PCT)
Prior art keywords
animal
formulation
water
macrocyclic lactone
aqueous formulation
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PCT/AU2006/001685
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English (en)
Inventor
Michael Joseph Findlay
Original Assignee
Bomac Animal Health Pty Limited
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Filing date
Publication date
Priority claimed from AU2005906236A external-priority patent/AU2005906236A0/en
Application filed by Bomac Animal Health Pty Limited filed Critical Bomac Animal Health Pty Limited
Priority to AU2006313007A priority Critical patent/AU2006313007C1/en
Publication of WO2007053902A1 publication Critical patent/WO2007053902A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION 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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/116—Heterocyclic compounds
    • A23K20/121—Heterocyclic compounds containing oxygen or sulfur as hetero atom
    • A23K20/126—Lactones
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/195—Antibiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
    • A23K50/75—Feeding-stuffs specially adapted for particular animals for birds for poultry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides

Definitions

  • the invention relates to treating or preventing an infestation by a parasite in or on an animal .
  • Macrocyclic lactones are used to treat infestations by endoparasites and ectoparasites in or on animals.
  • Macrocyclic lactones include the LL-F28249 compounds, the milbemycins and the avermectins .
  • the LL-F28249 family of compounds are natural endectocidal agents isolated from the fermentation broth of Streptomyces cyaneogriseus subsp. noncyanogenus .
  • the LL- F28249 family of compounds includes moxidectin.
  • milbemycins also known as the B-41 series of antibiotics, are naturally occurring macrocyclic lactones isolated from the microorganism Streptomyces hygroscopicus subsp. aureolacr ⁇ mosus.
  • the milbemycins include milbemycin A, milbemycin B, milbemycin D and others.
  • the avermectins also known as the C-076 family of compounds, are a family of closely related compounds produced by Streptomyces avermitilis or by synthetic or semisynthetic means. Members of the avermectin family include avermectin A Xa , A 2a , B la , B 2a , Ai b , A 2b , B ib and B 2b .
  • the avermectins include ivermectin, abamectin, doramectin, eprinomectin and others.
  • Ivermectin is a semisynthetic derivative of abamectin. Ivermectin contains at least 80% of 22,23- dihydroavermeetin Bi a and not more than 20% of 22,23- dihydroavermectin B ⁇ b .
  • Macrocyclic lactones including ivermectin, have been used to treat endoparasites, such as worms, and ectoparasites, such as lice and mites, in or on animals.
  • the formulations containing ivermectin approved for use in Australia for the treatment of parasites in or on pigs are formulations that are administered in admixture with the animal's feed or administered by subcutaneous injection.
  • Oral drenches containing ivermectin have been approved for use in Australia to treat parasites in or on horses, dogs, cattle and sheep.
  • Topical formulations containing a macrocyclic lactone have been approved for use in Australia to treat parasites in or on cattle.
  • the present invention provides a method of treating or preventing an infestation by a parasite in or on an animal, the method comprising providing an aqueous formulation comprising a macrocyclic lactone to the animal and allowing the animal to drink the aqueous formulation for an extended period.
  • the extended period during which the animal is allowed to drink the aqueous formulation is typically greater than about 6 days. In some embodiments, the extended period is from about 7 to about 14 days. In other embodiments, the extended period is about 3 months or about 100 days.
  • the macrocyclic lactone is present in the aqueous formulation at a concentration such that by drinking the aqueous formulation, the animal consumes a parasiticidally effective amount of the macrocyclic lactone.
  • the aqueous formulation comprises the macrocyclic lactone at a concentration such that when the aqueous formulation is drunk by the animal, the animal consumes about 50 to about 300 ⁇ g, for example, about 100 to about 300 ⁇ g, of the macrocyclic lactone per kg liveweight of the animal per day.
  • aqueous formulation is the only, or the principal, source of water available to the animal for drinking .
  • the macrocyclic lactone is in solution in the aqueous formulation.
  • the macrocyclic lactone may be any macrocyclic lactone.
  • the macrocyclic lactone may be an LL-F28249 compound (for example, moxidectin) , a milbemycin (for example, milbemycin A, milbemycin B or milbemycin D) , or an avermectin (for example, ivermectin, abermectin, doramectin or eprinomectin) .
  • the macrocyclic lactone is ivermectin.
  • the aqueous formulation comprises two or more macrocyclic lactones.
  • the animal is an intensively farmed animal kept in a controlled environment.
  • the animal may be a mammal or a bird.
  • the animal may, for example, be a pig, poultry (e.g. a chicken, turkey, guineafowl, duck or goose), cattle (e.g. cattle kept in a feed lot) or sheep.
  • the parasite may be a worm, lice or mite.
  • the parasite may be selected from one or more of gastrointestinal roundworms, kidney worms, lungworms, lice and mange mites.
  • the macrocyclic lactone is provided in a concentrate that is added to a source of water available to the animal for drinking, to produce the aqueous formulation.
  • the present invention provides a method of treating or preventing an infestation by a parasite in or on an animal, comprising mixing a formulation comprising: one or more macrocyclic lactones; one or more co-solvents;r one or more preservatives; one or more buffers; and water, with a source of water available to the animal for drinking to form an aqueous formulation comprising the one or more macrocyclic lactones, and allowing the animal to drink the aqueous formulation for an extended period.
  • the present invention provides a method of treating or preventing an infestation by a parasite in or on an animal, the method comprising administering a macrocyclic lactone in an amount of from about 50 to about 300 ⁇ g per kg liveweight of the animal per day to the animal in the animal's drinking water for an extended period.
  • the present invention provides a formulation comprising: one or more macrocyclic lactones; one or more co-solvents; one or more preservatives; one or more buffers; and water, when added to a source of water available to an animal for drinking .
  • the present invention provides a formulation comprising: one or more macrocyclic lactones; one or more co-solvents; one or more preservatives; one or more buffers; and water, when added to a source of water available to an animal for drinking to form the aqueous formulation used in the method of the first aspect of the present invention.
  • the formulation of the third or fourth aspect of the present invention may be added to the source of water available to the animal for drinking in an amount which results in the source of water comprising the one or more macrocyclic lactones in an amount of from about 250 to about 10,000 ⁇ g/L.
  • the one or more macrocyclic lactones is in solution in the formulation of the third or fourth aspect of the present invention.
  • the formulation of the third or fourth aspect of the present invention comprises: the macrocyclic lactone (s) in an amount of 0.1 to 100 g/L; the co-solvent (s) in an amount of 200 to 300 g/L; the preservative (s) in an amount of 20 to 50 g/L; and the buffer (s) in an amount of 8 to 15 g/L.
  • the present invention provides a method of treating or preventing an infestation by a parasite in or on an animal, the method comprising providing an aqueous formulation comprising a macrocyclic lactone to the animal and allowing the animal to drink the aqueous formulation for an extended period.
  • the aqueous formulation is prepared and provided to the animal by adding the macrocyclic lactone to a source of water available to the animal for drinking, that is, the macrocyclic lactone is added to the animal's drinking water.
  • the macrocyclic lactone is added to all sources of water available to the animal for drinking.
  • the macrocyclic lactone is added to the source of water available to the animal for drinking in an amount such that the resultant aqueous formulation comprises from about 250 to about 10,000 ⁇ g/L of the macrocyclic lactone.
  • the aqueous formulation comprises the macrocyclic lactone in an amount of from about 250 to about 2,500 ⁇ g/L.
  • the concentration of the macrocyclic lactone in the aqueous formulation is from about 500 to about 2,500 ⁇ g/L. In some embodiments, the concentration is less than about 2,000 ⁇ g/L.
  • the aqueous formulation comprises the macrocyclic lactone at a concentration such that when the animal drinks the aqueous formulation, the animal consumes about 50 to about 300 ⁇ g of the macrocyclic lactone per kg liveweight of the animal per day.
  • the extended period is typically a period of more than about 6 days. In some embodiments, the extended period is a period of more than about 7 days, for example, a period of from about 7 to about 100 days (e.g. from about 7 to about 14 days) . In other embodiments, for example where the animal is infected with a very persistent parasite, it may be more appropriate to treat the animal for a period of 14 to 21 days or longer. In some embodiments, the extended period is 7 days, 10 days, 14 days, 21 days or 28 days. In some embodiments, the extended period is 60 days, 90 days, 3 months or 100 days.
  • the macrocyclic lactone is ivermectin. However, other macrocyclic lactones may be used. In some embodiments, the aqueous formulation comprises two or more macrocyclic lactones.
  • the macrocyclic lactone is in solution in the aqueous formulation.
  • the methods of the present invention may be used to treat or prevent an infestation by any parasite that is killed or whose growth or reproduction is inhibited by a macrocyclic lactone.
  • ivermectin and other macrocyclic lactones can be used to treat or prevent infestations by worms, lice and mange mites in or on an animal.
  • the methods of the present invention can, for example, be used to treat or prevent infestations by large round worm ⁇ Ascris suum) , small brown stomach worm ⁇ Hyostrongylus rubidus) , nodule worm (Oesophagostomum spp) , stomach worm (Ascarops strongylina) , intestinal thread worm (Strongyloides ransomi) , kidney worms (Stephanurus dentatus) , lung worms (Metastrongylus spp) , lice ⁇ Haematopinus suis) and mange mites (Sarcoptes scabiel var.
  • the methods of the present invention can, for example, be used to treat or prevent infestations by round worm (Ascaridia galli) , caecal worm (Heterakis gallinae) , hairworm (Capillaria spp.), lice (Manacanthus stramineus; Menocan gallinae L.) and mites (Acarina spp.) in or on poultry.
  • the methods of the present invention can be used to treat or prevent infestations by these or similar parasites in or on other animals.
  • the animal may be any mammal or bird.
  • the animal may, for example, be a companion animal such as a dog or cat, 'a domestic animal such as a horse, pony, mule, llama, alpaca, pig, cow or sheep, or a zoo animal such as a primate, felid, canid, bovid or ungulate.
  • the animal is a pig, camel, deer, cow, sheep, goat, antelope, llama, alpaca, monkey, horse, donkey, mule, mouse, rat, rabbit, guinea pig or buffalo.
  • the animal is a chicken, turkey, guineafowl , duck or goose .
  • the macrocyclic lactone is present in the aqueous formulation at a concentration such that when the aqueous formulation is drunk by the animal, the animal consumes a parasiticidally effective amount of the macrocyclic lactone.
  • a parasite effective amount it is meant an amount effective to reduce the number of parasites in or on an animal or to prevent an infestation by a parasite in or on an animal.
  • the phrase "infestation by a parasite” includes a single parasite, that is, an animal has an infestation by a parasite if one or more individuals of that parasite species are present in or on the animal .
  • the parasiticidally effective amount of a macrocyclic lactone will vary with factors such as the type of animal treated, the particular parasite, the extent of the parasitic infestation, the age, weight and condition of the animal, the particular macrocyclic lactone used, and the duration of treatment.
  • a parasiticidally effective amount of a macrocyclic lactone would readily be able to be determined by a veterinarian.
  • a parasiticidally effective amount of a macrocyclic lactone may, for example, be determined by reference to conventional doses of the macrocyclic lactone used for the prevention or treatment of infestations by the parasite when the macrocyclic lactone is administered by another means, e.g. when administered as an oral drench.
  • a parasiticidally effective amount of ivermectin may be about 200 ⁇ g/kg liveweight per day.
  • the aqueous formulation comprising the macrocyclic lactone is a dilute solution of the macrocyclic lactone.
  • the concentration of the macrocyclic lactone in the aqueous formulation is typically less than 10,000 ⁇ g/L. In some embodiments, the concentration is from 500 to 2,500 ⁇ g/L. In some embodiments, the concentration is less than 2,000 ⁇ g/L.
  • the animal is allowed to drink the aqueous formulation over an extended period by making the aqueous formulation accessible to the animal for drinking, and leaving the animal in the presence of the aqueous formulation for the extended period under conditions such that the animal drinks the aqueous formulation.
  • the aqueous formulation comprising the macrocyclic lactone is the only source of water available to the animal throughout the extended period.
  • other sources of water may be available to the animal at the same time as the aqueous formulation comprising the macrocyclic lactone or at different times during the period of treatment, for example, at different times of the day.
  • the methods of the present invention are used to treat multiple animals simultaneously, eg a herd of pigs.
  • An advantage of the methods of the present invention is that they can be used to treat or prevent an infestation by a parasite in or on an animal with less handling of the animal than treatment regimens that involve the administration of a drench or an injection.
  • the administration of a drench or an injection to an animal can be stressful for the animal, which may reduce weight gain by the animal. For larger animals such as pigs, injecting the animal can also be stressful and dangerous for the animal handler.
  • administration of the macrocyclic lactone via the animal's drinking water over an extended period can be more effective in treating persistent parasites than treatment regimens involving the administration a single dose of the macrocyclic lactone.
  • An advantage of the methods of the present invention compared to administering the macrocyclic lactone, or other parasiticidal agents, in an in-feed medication mixed with the animal's feed is that the methods of the present invention allow for more accurate dosing as sick animals may not eat as much as a healthy animal but typically continue to drink. Further, by administering the macrocyclic lactone in the drinking water over an extended period, any short term fluctuations in water consumption by an animal will have little effect on the total dosage consumed by the animal over the extended period, minimising variations in the total dosage consumed by different animals in a herd of animals being treated by the method of the present invention.
  • a macrocyclic lactone in the water drunk by an animal further allows for more rapid commencement and cessation of administration of the macrocyclic lactone to a herd of animals than treatment using an in-feed medication, allowing the manager of the animals to respond quickly to changing circumstances.
  • a macrocyclic lactone can typically be quickly included in the drinking water for a herd of animals, and the inclusion of the macrocyclic lactone in the drinking water can also be quickly stopped.
  • an in-feed medication is used to treat a herd of animals, it is typically not economically viable to cease treatment by removing any uneaten feed that has been mixed with the in- feed medication and the feed mixed with the in-feed medication therefore typically remains available to the animals until all the feed has been consumed.
  • the aqueous formulation comprising the macrocyclic lactone is prepared shortly before the aqueous formulation is provided to the animal for drinking.
  • the aqueous formulation comprising the macrocyclic lactone is prepared by mixing a formulation comprising the macrocyclic lactone (referred to below as “the concentrated formulation") with water to form the aqueous formulation.
  • the concentrated formulation may, for example, comprise one or more macrocyclic lactones, one or more solvents, one or more preservatives, one or more buffers and water.
  • the concentrated formulation may also comprise other components such as flavours (e.g. sucrose, lactose, artificial sweeteners such as saccharine, salt or yeasty extracts) or colouring agents (e.g. food grade dyes) .
  • the method of the first aspect of the present invention comprises mixing a formulation comprising: one or more macrocyclic lactones; one or more so-solvents; one or more preservatives; one or more buffers; and water, with water, providing the resultant aqueous formulation to the animal and allowing the animal to drink the aqueous formulation over an extended period.
  • the concentrated formulation may, for example, contain the constituents referred to in Table 1 in the amounts referred to in Table 1.
  • co-solvent or co-solvents solubilise the macrocyclic lactone in the formulation and assist in maintaining the macrocyclic lactone in solution when the concentrated formulation is mixed with water.
  • Suitable co-solvents include propylene glycol, a mixture of propylene glycol and Ecoteric T80/Tween 80, a mixture of propylene glycol and propyl alcohol, or a mixture of propylene glycol and glycol formal.
  • Other suitable co-solvents include vegetable oils, myglyol 840 and mineral oils. A mixture of different co-solvents may be used.
  • the preservative or preservatives act to preserve the macrocyclic lactone during storage of the concentrated formulation and after the concentrated formulation has been mixed with water. Any preservative soluble in the concentrated formulation may be used. Suitable preservatives include benzyl alcohol, methyl paraben and propyl paraben .
  • the buffer or buffers maintain the pH of the concentrated formulation during storage of the concentrated formulation.
  • the buffers are typically selected to maintain the pH of the concentrated formulation at about 5.5 to 7.5.
  • formulations comprising: one or more macrocyclic lactones; one or more so-solvents ; one or more preservatives; one or more buffers; and water, can be prepared comprising 0.1 to 100 g/L of the macrocyclic lactone (s).
  • these formulations comprise water as a solvent.
  • Water is a relatively cheap solvent compared to the solvents used in some prior art formulations containing a macrocyclic lactone at a similar concentration.
  • such formulations, containing water as a solvent can be prepared which are stable during storage for many months. Without wishing to be bound by theory, it is believed that the presence of the preservative (s) and the buffer (s) in the formulation stabilise the macrocyclic lactone in the formulation.
  • An example of a concentrated formulation is the formulation set out in Table 2.
  • This concentrated formulation consists of the constituents referred to in Table 2 in the amounts referred to in Table 2.
  • the concentrated formulation set out in Table 2 may be mixed with water to form an aqueous formulation comprising ivermectin for use in the treatment or prevention of an infestation by a parasite such as large round worm ⁇ Ascaris suum) , small brown stomach worm (Hyostrongylus rubidus) , nodule worm (Oesophagostomum spp) , stomach worm ⁇ Ascarops strongylina) , intestinal thread worm ⁇ Strongyloides ransomi) , kidney worms ⁇ Stephanurus dentatus) , lung worms (Metastrongylus spp) , lice (Haematopinus suis) or mange mites (Sarcoptes scabiel var. suis) , in or on pigs in accordance with
  • the formulation set out in Table 2 is a micellar solution containing the ivermectin in solution.
  • the ivermectin When the formulation set out in Table 2 is mixed with water to form an aqueous formulation comprising less than about 10,000 ⁇ g/L of ivermectin, the ivermectin remains in solution in the aqueous formulation due to the low concentration of ivermectin in the aqueous formulation.
  • the macrocyclic lactone is present in the aqueous formulation at a concentration sufficient to treat or prevent an infestation by a parasite in or on an animal (i.e. a concentration sufficient to provide a parasiticidally effective amount of the macrocyclic lactone) when the aqueous formulation is drunk by the animal over an extended period.
  • concentration sufficient to provide a parasiticidally effective amount of the macrocyclic lactone will vary with the weight of the animal and the water consumption of the animal.
  • the typical weight range, typical daily water consumption and suitable concentrations of ivermectin in the animal's drinking water to provide a dose of about 100 ⁇ g of ivermectin per kg liveweight per day for various classes of pigs are set out in Table 3.
  • the concentrated formulation set out in Table 2 When the concentrated formulation set out in Table 2 is mixed with water to form an aqueous formulation comprising ivermectin for use in the treatment or prevention of an infestation by a parasite in or on pigs, the concentrated formulation is typically mixed with water in an amount to form an aqueous formulation containing a concentration of ivermectin sufficient to provide about 100 ⁇ g of ivermectin per kg liveweight per day when the aqueous formulation is drunk by the pigs.
  • the aqueous formulation is typically provided to the pigs for drinking for a period of from about 7 to 14 days, however, depending on the nature of the parasite being treated, this period can be extended.
  • the concentration of ivermectin in the aqueous formulation is typically within the ranges set out in Table 3.
  • the concentrated formulation is mixed with water to form the aqueous formulation shortly before the aqueous formulation is drunk by the pigs.
  • the aqueous formulation is drunk by the pigs within less than a day after the concentrated formulation is mixed with water to form the aqueous formulation.
  • An advantage of the methods of the present invention using the concentrated formulation set out in Table 2 to form the aqueous formulation comprising the macrocyclic lactone is that when the concentrated formulation is mixed with water to form an aqueous formulation comprising ivermectin in an amount of less than about 10,000 ⁇ g/L, the ivermectin is in solution in the water.
  • the ivermectin when the aqueous formulation is consumed by a pig, the ivermectin is in a form that can be readily absorbed by the pig.
  • feed mixed with an in-feed medication containing ivermectin is consumed by a pig the ivermectin needs to be dissolved before it can be absorbed by the pig.
  • the aqueous formulation comprising the macrocyclic lactone is provided to the animal (s) for drinking over an extended period of time. If the aqueous formulation comprising the macrocyclic lactone is the only source of water available to the animal (s) , providing the aqueous formulation to the animal (s) over ' an extended period advantageously minimises the effects of any fluctuations in day to day water consumption (for example due to changes in temperature) on the total dose of the macrocyclic lactone consumed by the animal (s) over the treatment period compared to shorter treatment periods.
  • the aqueous formulation may be provided to the animal (s) in a manner that results in the animal (s) consuming a predetermined amount of the macrocyclic lactone per day, irrespective of any fluctuation in water consumption from day to day.
  • the aqueous formulation comprising the macrocyclic lactone may be supplied to the animal (s) using a large gravity feed medication tank which will be drunk until empty, and then non-medicated water supply would commence for the remainder of the day.
  • This method may advantageously reduce the overall cost of the treatment program by ensuring that the animals are not over-dosed with the macrocyclic lactone.
  • the aqueous formulation comprising the macrocyclic lactone is prepared by mixing a concentrated solution of the macrocyclic lactone with water using a proportionating pump, such as those sold under the trade mark DOSATRON (manufactured by DOSATRON INTERNATIONAL, RUE PASCAL, B. P. 6, 33370 TRESSES, BORDEAUX, FRANCE) .
  • DOSATRON manufactured by DOSATRON INTERNATIONAL, RUE PASCAL, B. P. 6, 33370 TRESSES, BORDEAUX, FRANCE
  • Such pumps are currently used for medicating drinking water with products such as vitamins, electrolytes, and nutritional supplements. These pumps are installed in the water supply line, and operate without electricity, using water pressure as the power source.
  • the water pressure activates the injector, which takes up a percentage of the concentrated solution of the product to be mixed with the water from a stock solution container. Inside the injector, the concentrate is mixed with the water, and the water pressure forces the solution downstream.
  • the amount of concentrate is directly proportional to the
  • Example 1 Comparison of the method of the present invention and an in-feed control program
  • Trials were carried out to compare the efficacy of administering ivermectin in the drinking water of pigs over an extended period with an in-feed treatment regimen in inhibiting intestinal parasitism due to Ascaris suum in pigs.
  • Treatment group (A) was administered ivermectin in the pigs' drinking water at a dosage of 100 ⁇ g/kg liveweight/day for 7 days ending 7 days prior to slaughter.
  • the pigs had free access to the medicated drinking water and free access to feed throughout this 7 day period.
  • the pigs had free access to unmedicated drinking water and free access to food.
  • Treatment group (B) was treated with the commercial product sold under the name "Wormtec" by Morantel in admixture with the pigs' feed.
  • the product was mixed with the pigs' feed in accordance with the directions on the label for the product .
  • the label states that the product contains 3O g morantel citrate per kg.
  • the product was mixed with the feed at 1 kg per tonne of finished feed.
  • the pigs had free access to the medicated feed until all this feed had been consumed (all the medicated feed was consumed before 7 days before slaughter) .
  • the pigs Prior to commencement of the administration of the medicated feed and after all the medicated feed had been consumed, the pigs had free access to unmedicated feed. Throughout the trial, the pigs had free access to drinking water.
  • Example 2 Comparison of the method of the present invention with control, in-feed and injection treatment regimens
  • the trial pigs were relocated to individual pens and introduced to a fully fed ration and water in individual drinkers. Pens were raised with metal mesh floors and were vigorously cleaned at least once daily (using a high pressure water hose) to prevent any further infections occurring post relocation. Individual daily water consumption and feed intake were monitored from day -7 to day 0 to confirm normal water intake and feed intake and to assist with dose calculations. Individual faecal samples were collected between day -3 and -1 (inclusive) , and individual strongyle faecal egg counts performed (along with a single bulk coproculture for larval differentiation) .
  • trial pigs were ranked (from highest to lowest) on individual strongyle faecal egg counts, sequentially blocked (into fours) and randomly allocated from within each block to four treatment groups, each of twelve pigs. Allocation was such that each group had a similar group mean strongyle faecal egg count and range of egg counts within the group.
  • Trial pigs in Group 2 were treated with the test formulation (the formulation set out on Table 2) for seven days in their drinking water to provide a dosage of ivermectin of 100 ⁇ g/kg liveweight/day . Medication was mixed up and supplied once daily. Water plus medication was supplied in individual drinkers and individual daily water intake assessment (Group 2 only) continued from day 0 to 6 inclusive, to determine actual administered dose rates .
  • Pigs in Group 3 commenced treatment with a registered ivermectin-based in feed medication (Ivomec Premix for Pigs ® ) , at 100 ⁇ g/kg in feed. Medication was mixed up according to label directions in the pigs' feed and supplied once daily from day 0 to day 6 inclusive. Medicated feed was supplied in individual feeders and individual daily feed intake (Group 3 only) continued from day 0 to day 6 inclusive, to determine actual administered dose rates.
  • a registered ivermectin-based in feed medication Ivomec Premix for Pigs ®
  • Medication was mixed up according to label directions in the pigs' feed and supplied once daily from day 0 to day 6 inclusive.
  • Medicated feed was supplied in individual feeders and individual daily feed intake (Group 3 only) continued from day 0 to day 6 inclusive, to determine actual administered dose rates.
  • Pigs in Group 4 were treated once on day 0 (via subcutaneous injection) with Ivomec Antiparasitic Injection for Pigs ® according to day 0 bodyweight, at the label dose rate (300 ⁇ g/kg) .
  • HPLC validated analytical method no. PHARMl was used for Ivermectin active ingredient content testing and CIPAC methods for examination of physical parameters.

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Abstract

La présente invention décrit une méthode pour traiter ou empêcher une invasion parasitaire dans ou sur un animal. La méthode consiste à administrer une formule aqueuse comprenant une lactone macrocyclique à l'animal et à permettre à l'animal de boire la formule aqueuse sur une période prolongée.
PCT/AU2006/001685 2005-11-10 2006-11-10 Méthode pour traiter des parasites WO2007053902A1 (fr)

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WO2015091898A1 (fr) * 2013-12-20 2015-06-25 Intervet International B.V. Compostions d'isoxazoline et leur utilisation dans la prévention ou le traitement d'infestations parasitaires chez des animaux
US10272071B2 (en) 2013-12-20 2019-04-30 Intervet Inc. Use of isoxazoline derivatives for the treatment or prevention of arthropod infestations in poultry
RU2791637C2 (ru) * 2013-12-20 2023-03-13 Интервет Интернэшнл Б.В. Изоксазолиновые композиции и их применение в профилактике или лечении паразитарных инвазий животных

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015091898A1 (fr) * 2013-12-20 2015-06-25 Intervet International B.V. Compostions d'isoxazoline et leur utilisation dans la prévention ou le traitement d'infestations parasitaires chez des animaux
US10272071B2 (en) 2013-12-20 2019-04-30 Intervet Inc. Use of isoxazoline derivatives for the treatment or prevention of arthropod infestations in poultry
RU2688919C1 (ru) * 2013-12-20 2019-05-23 Интервет Интернэшнл Б.В. Изоксазолиновые композиции и их применение в провилактике или лечении паразитарных инвазий животных
US10456358B2 (en) 2013-12-20 2019-10-29 Intervet Inc. Isoxazoline compositions and use thereof in the prevention or treatment of parasite infestations in animals
US10653675B2 (en) 2013-12-20 2020-05-19 Intervet Inc. Use of isoxazoline derivatives for the treatment or prevention of arthropod infestations in poultry
US11304934B2 (en) 2013-12-20 2022-04-19 Intervet Inc. Use of isoxazoline derivatives for the treatment or prevention of arthropod infestations in poultry
RU2791637C2 (ru) * 2013-12-20 2023-03-13 Интервет Интернэшнл Б.В. Изоксазолиновые композиции и их применение в профилактике или лечении паразитарных инвазий животных
US11883530B2 (en) 2013-12-20 2024-01-30 Intervet Inc. Isoxazoline compositions and use thereof in the prevention or treatment of parasite infestations in animals
EP4306168A3 (fr) * 2013-12-20 2024-03-13 Intervet International B.V. Compositions d'isoxazoline et leur utilisation dans la prévention ou le traitement d'infestations de parasites chez des animaux

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