[go: up one dir, main page]

WO2024189101A1 - Composés d'arylaminobenzamide ou d'isoxazoline destinés à être utilisés dans la lutte contre une infestation parasitaire chez un poisson - Google Patents

Composés d'arylaminobenzamide ou d'isoxazoline destinés à être utilisés dans la lutte contre une infestation parasitaire chez un poisson Download PDF

Info

Publication number
WO2024189101A1
WO2024189101A1 PCT/EP2024/056706 EP2024056706W WO2024189101A1 WO 2024189101 A1 WO2024189101 A1 WO 2024189101A1 EP 2024056706 W EP2024056706 W EP 2024056706W WO 2024189101 A1 WO2024189101 A1 WO 2024189101A1
Authority
WO
WIPO (PCT)
Prior art keywords
fish
modoflaner
caligus
isoxazoline
salmon
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.)
Pending
Application number
PCT/EP2024/056706
Other languages
English (en)
Inventor
Bertrand Havrileck
Regina LIZUNDIA GORBEA
Stéphane Bonneau
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.)
Virbac SA
Original Assignee
Virbac SA
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 Virbac SA filed Critical Virbac SA
Publication of WO2024189101A1 publication Critical patent/WO2024189101A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Images

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A40/00—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
    • Y02A40/80—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in fisheries management
    • Y02A40/81—Aquaculture, e.g. of fish

Definitions

  • the present invention relates to Modoflaner, an arylaminobenzamide compound, for its use in controlling a parasite infestation on a fish and to an isoxazoline for its use in controlling a parasite infestation on a fish, said isoxazoline being administered parenterally.
  • parasitic copepods are common on cultured and wild marine finfish, and are vastly described in the literature regarding their taxonomy and host ranges.
  • Sea lice are ectoparasites of the order Siphonostomatoida or of the family Argulidae. They are the most commonly reported species on marine and brackish water cultured fish throughout the world, accounting for approximately 61% of all reports. Members of this family have been responsible for most of the documented disease outbreaks. They affect fish, particularly farmed fishes of the Salmonidae family, negatively by feeding on the mucus, skin, tissue, and blood of the fish host. Sea lice can cause significant harm (i.e., serious fin damage, skin erosion, bleeding, and open wounds) to host fish, due to their attachment and feeding activities. Additionally, sea lice can cause chronic stress response in fish, which in turn can make them susceptible to other diseases. In addition, it appears that the sea lice have immunomodulatory effects on the host fish and can function as a vector in the transmission of other fish diseases.
  • Severe infestation kills the fish. Mortality rates of over 50%, based on sea lice infestation, have been reported from Norwegian fish farms. In a first phase, sea lice infestation is seen in the appearance of the parasites attached to the fish and later, even more clearly, from the damage caused to skin and tissue. The most severe damage is observed in smolts which are just in the phase in which they change from fresh water to sea water. The situation is made even worse by the specific conditions in the fish farms, where fish, for example salmon, of different age groups but of the same weight class are kept together; where fouled nets or cages are used; where high salt concentrations are to be found; and/or where flow through the nets and cages is minimal and the fish are kept in a very narrow space.
  • Infestation with sea lice is considered one of the most important disease problems in the farming of fishes of the Salmonidae family, especially Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss).
  • Atlantic salmon Salmo salar
  • rainbow trout Oncorhynchus mykiss.
  • lower classification ratings of slaughtered fish and reduced growth rate due to reduced feed intake contribute to the economic losses.
  • sea lice Infestation with sea lice can also occur in other fish species, for example, sea bass, tilapia, carp, and the like. In fact, sea lice are meanwhile widely prevalent and encountered in all fish farms.
  • sea-lousicide treatments are administered topically in bathes or dips or orally in medicated feed which results in the dispersion of the active ingredient in the environment.
  • parenteral administration such as intraperitoneal or intramuscular administration, is environmentally safe.
  • one aim of the present invention is the provision of new treatment options to control parasite infestation, in particular sea lice infestations, on fish, particularly in farmed fish populations.
  • Another aim of the present invention is to provide new treatments that can be used for prolonged control of parasites on fish, for example for at least one, two, three months or more.
  • Another aim of the present invention is to provide new treatments that are selective against the target parasite and/or capable of treating parasite populations, in particular sea lice populations, showing resistance or reduced sensitivity to the current products.
  • Another aim of the present invention is to provide new treatments that are safe to the fish recipients, their human caretakers and the environment.
  • an "infestation” refers to the presence of parasites on the fish in numbers that pose a risk of nuisance or harm to said fish.
  • controlling or control of a parasite infestation encompasses preventing or treating or both preventing and treating parasite infestations.
  • the effect of the treatment can manifest itself directly by killing the parasites, either immediately or after some time has elapsed, or indirectly, for example by partially or completely inhibiting the development of parasites or reducing the number of eggs laid.
  • preventing or prevention of a parasite infestation means avoiding the presence of parasites on a fish in numbers that pose a risk of nuisance or harm to said fish.
  • the parasite infestation may be prevented by administering an effective dose of Modoflaner or the isoxazoline to a non-infested fish, e.g. before said fish enters in contact with a parasite or by administering to a fish that is or has been infested by a parasite an effective dose of Modoflaner or the isoxazoline to prevent a new parasite infestation or a re-infestation by the offspring of the infesting parasite.
  • treating or treatment of a parasite infestation means reducing the number of parasites already present on the fish.
  • the parasite infestation can be treated by administering to an infested fish an effective dose of Modoflaner or the isoxazoline.
  • an “effective dose” refers to the amount of Modoflaner or the isoxazoline that needs to be administered to reduce the number (or count) of the existing or potential parasites on the fish by at least about 5%.
  • the dose is considered effective when the number of existing or potential parasites on the fish is reduced by at least about 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89 %, more preferably by at least about 90%.
  • the dose is considered effective when the number of existing or potential parasites on the fish is reduced by
  • the term "about” refers in particular to a range of values ⁇ 10% of a specific value.
  • the expression “about 20” includes the values 20 ⁇ 10%, i.e. the values 18 to 22.
  • an “effective dose” of Modoflaner or the isoxazoline refers to the amount of Modoflaner or the isoxazoline that needs to be administered to reduce or maintain the number (or count) of gravid (or ovigerous) female sea lice or adult sea lice below a regulatory threshold, i.e. a count of sea lice over which a treatment must be administered.
  • thresholds are 0.1 gravid female / fish during outmigration period of wild salmon, 0.2 gravid female / fish during outmigration period of wild salmon and 0.5 gravid female / fish during the rest of the year, 0.3-0.5 gravid female / fish during outmigration period of wild salmon and 2.0 gravid female / fish during the rest of the year, 1.5 gravid female / fish, 3.0 gravid female / fish, 3.0 adult sea lice.
  • louse refers to a fish parasite of the order Siphonostomatoida or of the family Argulidae.
  • fish refers to the taxonomic class Chondrichthyes (cartilaginous fishes, e.g., sharks and rays) and Osteichthyes (bony fishes) which live in water, have gills or mucus-covered skin for respiration, fins, and may have scales.
  • Chondrichthyes cartilaginous fishes, e.g., sharks and rays
  • Osteichthyes bony fishes which live in water, have gills or mucus-covered skin for respiration, fins, and may have scales.
  • crystalline modification IV of Modoflaner is synonymous with “crystalline form IV of Modoflaner”, or “crystalline polymorphic form IV of Modoflaner” and means in particular Modoflaner comprising from 20 to 100% ( e.g. 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100%) in weight of crystalline
  • fish body weight refers to the bodyweight of an individual fish or weight of the fish biomass.
  • the present invention concerns a parasiticide isoxazoline, preferably selected from the group consisting in fluralaner, afoxolaner, sarolaner and lotilaner, for use in controlling a parasite infestation on a fish, wherein the isoxazoline is administered parenterally to the fish.
  • the isoxazoline may be administered by intraperitoneal injection (e.g. an injection given into the mid ventral line, just below vent), subcutaneous injection, intramuscular injection (e.g. injection into the epiaxial musculature, generally approximately mid-way between the mid-dorsal line and the lateral line), or injection into the dorso-median sinus (e.g. an injection in the mid-dorsal line in the angle at the caudal margin of the cranial dorsal fin).
  • intraperitoneal injection e.g. an injection given into the mid ventral line, just below vent
  • subcutaneous injection e.g. injection into the epiaxial musculature, generally approximately mid-way between the mid-dorsal line and the lateral line
  • injection into the dorso-median sinus e.g. an injection in the mid-dorsal line in the angle at the caudal margin of the cranial dorsal fin.
  • the isoxazoline is preferably administered intraperitoneally or intramuscularly.
  • the isoxazoline is preferably fluralaner.
  • the isoxazoline is administered at a dose ranging from 1 to 100 mg/kg, preferably from 10 to 90 mg/kg, more preferably from 25 to 50 mg/kg, in particular about 40 mg/kg, of fish bodyweight.
  • the isoxazoline especially fluralaner, is administered at a dose ranging from about 40 mg/kg to about 120 mg/kg of fish bodyweight.
  • the isoxazoline is administered at a dose ranging from about 50, 60, 70, 80 or 90 mg/kg to about 120 mg/kg of fish bodyweight.
  • the parasite may be any fish-parasitic crustacean, notably a sea louse. It should be understood that, in the present invention, only parasites that are parasitic to fish are contemplated.
  • the sea louse may in particular belong to the family Argulidae or the order Siphonostomatoida.
  • the parasite belonging to the genus Argulus are of relevance, in particular Argulus foliaceus .
  • the family Caligidae includes the genus Lepeophtheirus and Caligus , in particular the species Caligus acanthopagri, Caligus antennatus, Caligus brevicaudatus, Caligus clemensi, Caligus curtus, Caligus dussumieri, Caligus elongatus, Caligus epidemicus, Caligus fugu, Caligus lalanderi, Caligus latigenitalis, Caligus longicaudatus, Caligus longipedis, Caligus minimus, Caligus multispinosus, Caligus nanhaiensis, Caligus orientalis, Caligus oviceps, Caligus pageti, Caligus patulu, Caligus pelamydis, Caligus punctatus, Caligus rogercresseyi, Caligus rotundigenitalis, Caligus spinosus, Caligus stromii, Caligus teres, Lepe
  • the parasite is a sea louse preferably selected from the group consisting in Lepeophtheirus salmonis, Caligus clemensi, Caligus curtus, Caligus dussumieri, Caligus elongates, Caligus longicaudatus, Caligus rogercresseyi or Caligus stromii , more preferably Lepeophtheirus salmonis, Caligus elongates, or Caligus rogercresseyi .
  • the parasite is a haematophagous parasite, notably a haematophagous sea louse, for example Lepeophtheirus salmonis .
  • the parasite infestation may be with several developmental stages like copepodites, chalimus, pre-adult, adult sea lice or a mixed infestation with various stages.
  • the fish include food fish, breeding fish, aquarium, pond, river, reservoir fish of all ages occurring in freshwater, sea water and brackish water.
  • fish includes fishes of the Salmonidae family, in particular salmons, trouts, chars, freshwater whitefishes, graylings; or from sea breams, porgies, breams, scats, ray-finned fishes, cichlids, oreochromine cichlids, flounders, cods, groupers, basses, black basses, temperate basses, seabasses, for example Asian seabasses, tilapias, mullets, milkfishes, pufferfishes, pompanos, jacks, amberjacks, lates, grunters, perciformes, rabbitfishes, perches, cobias, carps, catfishes, smelts, sweetfishes, rockfishes, chubs, eels, gour
  • salmons such as Atlantic salmon ( Salmo salar ), coho salmon ( Oncorhynchus kisutch ), humpback salmon ( Oncorhynchus gorbuscha ), chum salmon ( Oncorhynchus keta ), chinook salmon ( Oncorhynchus tshawytscha ), masu salmon ( Oncorhynchus masou ), Taiwanese salmon ( Oncorhynchus masou formosanum ), Sockeye salmon or Red salmon ( Oncorhynchus nerka); trouts (genus Oncorhynchus), such as rainbow trout ( Oncorhynchus mykiss ), brown trout ( Salmo trutta ), coastal cutthroat trout ( Oncorhynchus or Salmo clarkii clarkii ), sea trout ( Oncorhynchus my
  • the fish is preferably selected from the group consisting in Atlantic salmon ( Salmo salar ), Coho salmon ( Oncorhynchus kisutch ), Chinook salmon ( Oncorhynchus tshawytscha ) or rainbow trout ( Oncorhynchus mykiss ), notably Atlantic salmon ( Salmo salar ).
  • the fish is preferably selected from the group consisting in Atlantic salmon ( Salmo salar ), Coho salmon ( Oncorhynchus kisutch ), Chinook salmon ( Oncorhynchus tshawytscha ) or rainbow trout ( Oncorhynchus mykiss ), notably Atlantic salmon ( Salmo salar ), and the parasite is a haematophagous parasite, notably a haematophagous sea louse, for example Lepeophtheirus salmonis .
  • the isoxazoline is preferably administered to juvenile fish.
  • the fish is a salmon and the isoxazoline is administered to a smolt, before said smolt is transferred from fresh-water tanks or cages to sea water cages.
  • the smolt weighs between 50 and 350 g, preferably 50 and 150 g, more preferably between 80 and 120 g when the isoxazoline is administered.
  • the isoxazoline may be administered to the fish in a formulation that is a solution (the isoxazoline is dissolved in the formulation), a suspension (the isoxazoline is dissolved in the formulation) or is a long-injectable implant.
  • the isoxazoline is formulated in a non-aqueous polar solvent.
  • the isoxazoline may be present in the formulation in an amount of 10-1000 mg/ml of the formulation, preferably of 100 to 500 mg/ml of the formulation.
  • the formulation may comprise a solvent having solubility for the isoxazoline, in particular selected from the group consisting in glycofurol (tetraglycol), acetone, acetonitrile, benzyl alcohol, butyl diglycol, dimethylacetamide, dimethylsulfoxide, dimethylformamide (DMF), N,N-diethyl-3-methylbenzamide, dipropylene glycol n-butyl ether, ethyl alcohol, isopropanol, methanol, phenylethyl alcohol, isopropanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethylaceamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols, propylene glycol, N-methylpyrrolidone (NMP), 2-pyrrolidone, limonene, eucalyptol, diethylene glycol monoethyl ether, ethylene glycol, diethyl phthal
  • the non-aqueous polar solvent comprises DMSO.
  • the non- aqueous polar solvent may be present in the formulation in an amount of 5-100% by weight, and preferably may be present in an amount of 10-50% by weight.
  • the formulation may comprise a solubilizer, in particular selected from Cremophor EL, Tween, Brij C10, Kolliphor HS15, Cremophor RH40 and mixtures thereof.
  • the solubilizer may be present in the formulation in an amount of 10-95% by weight, preferably may be present in an amount of 30-60% by weight.
  • the formulation may also comprise a hydrophilic polymer, in particular having a molecular weight in the range of 50-2000, such as 100-1800.
  • the hydrophilic polymer is preferably a PEG (polyethylene glycol), a PEG derivative, PPG (polypropylene glycol), or a PPG derivative and mixtures thereof.
  • the hydrophilic polymer is selected from the group consisting in monofunctional PEG, a homobifunctional PEG, a heterobifunctional PEG, a multi-arm PEG, a star-PEG, a polyether, a homobifunctional PPG, or a monofunctional PPG.
  • the hydrophilic polymer comprises PEG, and the hydrophilic polymer may be PEG having a molecular weight of between 200 and 1000 g/mol.
  • the hydrophilic polymer comprises PEG300, PEG400, or PEG600.
  • the hydrophilic polymer may be present in the formulation in an amount of 5-100% by weight, preferably in an amount of about 70-90%, most preferably about 85% by weight.
  • the formulation may comprise a combination of one or more hydrophilic polymer(s) and one or more non-aqueous polar solvent(s), preferably 75-90% by weight of one or more hydrophilic polymer(s) and 10-25% by weight of one or more non-aqueous polar solvent(s).
  • the hydrophilic polymer is present in the formulation in a total amount of about 85% by weight
  • the non-aqueous polar solvent is present in the formulation in a total amount of about 15% by weight.
  • xx mg/ml of isoxazoline refers to the amount of isoxazoline (in mg) that is comprised in 1 ml of the formulation, i.e. in the one or more non-aqueous polar solvent(s), one or more hydrophilic polymer(s) and mixtures thereof.
  • the isoxazoline may be administered in the form of an implant, notably in the form of microspheres, in particular a poly(lactic-co-glycolic acid) (PLGA)- and/or poly(lactic acid) (PLA)-based microspheres.
  • PLGA poly(lactic-co-glycolic acid)
  • PLA poly(lactic acid)
  • the isoxazoline When administered at a dose ranging from 1 to 100 or 120 mg/kg, preferably from 10 to 90 mg/kg, more preferably from 25 to 50 mg/kg, in particular about 40 mg/kg or ranging from about 40 mg/kg to about 120 mg/kg, of fish bodyweight, the isoxazoline, especially fluralaner, provides effective control (e.g.
  • the first aspect also encompasses the use of an isoxazoline for controlling a parasite infestation on a fish, as described above.
  • the first aspect also encompasses also a method of controlling a parasite infestation on a fish as described above, which comprises administering to the fish an effective dose of the isoxazoline, as described above.
  • the first aspect further encompasses the use of an isoxazoline for the manufacture of a medicament intended for controlling a parasite infestation on a fish, as described above.
  • the present invention concerns Modoflaner, for use in controlling a parasite infestation on a fish.
  • a specific arylaminobenzamide compound namely Modoflaner
  • Mode (I) refers to (6-fluoro-N-(3-(2-iodo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenylcarbamoyl)-2-fluoro-phenyl)-nicotinamide, having the following formula: Formula (I)
  • Modoflaner can be prepared following the procedure described in WO2019/059412.
  • Acid and base salts can typically be formed by, for example, mixing Modoflaner with an acid or base, respectively, using various known methods in the art.
  • a salt of Modoflaner is intended to be administered in vivo (i.e., to the fish) for a therapeutic benefit
  • the salt is pharmaceutically acceptable.
  • an acid addition salt can be prepared by reacting a free base compound with an approximately stoichiometric amount of an inorganic or organic acid.
  • salts refers notably to acid addition salts of the pyridine residue of Modoflaner.
  • Modoflaner may be formulated into stable complexes with a solvent, such that the complex remains intact after the non-complexed solvent is removed. These complexes are often referred to as "solvates.” It is particularly desirable to form stable hydrates with water as the solvent.
  • a solvate of Modoflaner as mentioned above may be formed by aggregation of Modoflaner with solvent molecules such as water, alcohols, for example ethanol, aromatic solvents such as toluene, ethers, halogenated organic solvents such as dichloromethane, preferably in a definite proportion by weight.
  • Modoflaner may be made as various crystal polymorphs. Polymorphism is important in the development of veterinary products since different crystal polymorphs or structures of the same molecule can have vastly different physical properties and biological performances.
  • Modoflaner is crystalline modification IV of Modoflaner as described in WO2022/101502.
  • the parasite may be any fish-parasitic crustacean, notably a sea louse.
  • Fish parasites such as copepods, in particular sea lice, have both free-swimming (planktonic) and parasitic life stages, all separated by moults. It should be understood that, in the present invention, only parasites that are parasitic to fish are contemplated.
  • the sea louse may in particular belong to the family Argulidae or the order Siphonostomatoida.
  • the parasites belonging to the genus Argulus are of relevance, in particular Argulus foliaceus .
  • the family Lernanthropidae includes Lernanthropus spp. Species such as Lernanthropus kroyeri, Lernanthropus callinomymicola, Lernanthropus indefinitus, Lernanthropus cynoscicola and Lernanthropus gisleri. These parasites are of particular concern in Mediterranean fish farming.
  • the family Caligidae includes the genus Lepeophtheirus and Caligus , in particular the species Caligus acanthopagri, Caligus antennatus, Caligus brevicaudatus, Caligus clemensi, Caligus curtus, Caligus dussumieri, Caligus elongatus, Caligus epidemicus, Caligus fugu, Caligus lalanderi, Caligus latigenitalis, Caligus longicaudatus, Caligus longipedis, Caligus minimus, Caligus multispinosus, Caligus nanhaiensis, Caligus orientalis, Caligus oviceps, Caligus pageti, Caligus patulu, Caligus pelamydis, Caligus punctatus, Caligus rogercresseyi, Caligus rotundigenitalis, Caligus spinosus, Caligus stromii, Caligus teres, Lepe
  • the parasite is at least one of Lepeophtheirus salmonis, Caligus clemensi, Caligus curtus, Caligus dussumieri, Caligus elongates, Caligus longicaudatus, Caligus rogercresseyi or Caligus stromii , more preferably Lepeophtheirus salmonis, Caligus elongates, or Caligus rogercresseyi .
  • These parasites are of particular concern in Salmonidae farming.
  • the parasite infestation may be with several developmental stages like copepodites, chalimus, pre-adult, adult sea lice or a mixed infestation with various stages.
  • the fish include food fish, breeding fish, aquarium, pond, river, reservoir fish of all ages occurring in freshwater, sea water and brackish water.
  • fish includes fishes of the Salmonidae family, in particular salmons, trouts, chars, freshwater whitefishes, graylings; or from sea breams, porgies, breams, scats, ray-finned fishes, cichlids, oreochromine cichlids, flounders, cods, groupers, basses, black basses, temperate basses, seabasses, for example Asian seabasses, tilapias, mullets, milkfishes, pufferfishes, pompanos, jacks, amberjacks, lates, grunters, perciformes, rabbitfishes, perches, cobias, carps, catfishes, smelts, sweetfishes, rockfishes, chubs, eels, gour
  • salmons such as Atlantic salmon ( Salmo salar ), coho salmon ( Oncorhynchus kisutch ), humpback salmon ( Oncorhynchus gorbuscha ), chum salmon ( Oncorhynchus keta ), chinook salmon ( Oncorhynchus tshawytscha ), masu salmon ( Oncorhynchus masou ), Taiwanese salmon ( Oncorhynchus masou formosanum ), Sockeye salmon or Red salmon ( Oncorhynchus nerka); trouts (genus Oncorhynchus), such as rainbow trout ( Oncorhynchus mykiss ), brown trout ( Salmo trutta ), coastal cutthroat trout ( Oncorhynchus or Salmo clarkii clarkii ), sea trout ( Oncorhynchus my
  • the fish is Atlantic salmon ( Salmo salar ), Coho salmon ( Oncorhynchus kisutch ), Chinook salmon ( Oncorhynchus tshawytscha ) or a trout, in particular rainbow trout ( Oncorhynchus mykiss ), notably Atlantic salmon ( Salmo salar ).
  • Modoflaner may be administered to the fish by any route which provides the sought control of parasite infestation, including enteral administration, notably oral administration, topical administration, or parenteral administration.
  • a number of factors are considered, including, but not limited to the species of fish; the degree of parasite infestation; the response of the fish population; the mode of administration; the bioavailability characteristics of the preparation administered; the dose regimen selected; the use of concomitant medication and the duration of the sought effect.
  • Modoflaner may be administered in a medicated feed (freely taken by the fish or by gavage) or in a medicated water (the drug is dissolved or suspended in the water surrounding the fish).
  • compositions suitable for oral administration notably include a medicated fish feed (e.g. a nutritionally complete feed comprising Modoflaner) typically in the form of granules or pellets and a medicated premix that is added to fish feed, to obtain a medicated fish feed.
  • a medicated fish feed e.g. a nutritionally complete feed comprising Modoflaner
  • a medicated premix typically in the form of granules or pellets
  • a medicated premix that is added to fish feed, to obtain a medicated fish feed.
  • the dose of Modoflaner is in the range of about 0.01 to 500 mg/kg, in particular 1 to 100 mg/kg, of the fish bodyweight.
  • the medicated fish feed may be administered on one day or over the course of several days, until the amount of Modoflaner ingested by the fish is sufficient to provide the sought control of parasite infestation for the desired period.
  • the medicated fish feed is administered to the fish through multiple feedings (i.e. a divided daily dose).
  • a medicated fish feed comprising Modoflaner can be administered 1 time daily, for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, or 15 days, notably 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, or 15 days.
  • Modoflaner may be administered by immersion or dipping (the fish is transferred from its pen or basin to a tank containing water in which Modoflaner is dissolved or suspended and allowed to stay in this tank during a period sufficient to reach an effective dose of Modoflaner), bath treatment (Modoflaner is dissolved and/or suspended in the water where the fish lives), flushing (the fish is immersed in running water or a raceway system wherein Modoflaner is dissolved or suspended), hyperosmotic infiltration (the fish is placed in an hypertonic solution then in water in which Modoflaner is suspended or dissolved or the fish is placed in a hypertonic solution or suspension of Modoflaner), transdermal application, inhalation or intranasal route.
  • immersion or dipping the fish is transferred from its pen or basin to a tank containing water in which Modoflaner is dissolved or suspended and allowed to stay in this tank during a period sufficient to reach an effective dose of Modoflaner
  • bath treatment Mode of the water where the fish lives
  • flushing the
  • compositions for immersion, dipping, bath treatment, flushing, hyperosmotic infiltration, transdermal application, inhalation or intranasal route include powders, granulates, solutions, emulsions micro/nanoemulsions, emulsifiable concentrates, suspensions, nanosuspensions, or suspension concentrates, tablets, water-soluble films or films.
  • the effective dose of Modoflaner is comprised between about 2ppb to about 500ppb, preferably between 20 and 250 ppb, more preferably between 50 and 150 ppb, based on the amount of water used for bathing, immersing, dipping or flushing the fish.
  • the concentration of Modoflaner during administration to the fish by immersion, dipping, bath treatment, or flushing depends on the manner and duration of treatment and also on the age and condition of the fish being treated.
  • a typical immersion, dipping, bath treatment, or flushing time ranges from about 15 minutes to about 4 hours, preferably from about 15 minutes to 2 hours, and more preferably from about 30 minutes to about 1 hour.
  • Modoflaner may be administered by intraperitoneal injection (e.g. an injection given into the mid ventral line, just below vent), subcutaneous injection, intramuscular injection (e.g. injection into the epaxial musculature, generally approximately mid-way between the mid-dorsal line and the lateral line), or injection into the dorso-median sinus (e.g. an injection in the mid-dorsal line in the angle at the caudal margin of the cranial dorsal fin).
  • intraperitoneal injection e.g. an injection given into the mid ventral line, just below vent
  • subcutaneous injection e.g. injection into the epaxial musculature, generally approximately mid-way between the mid-dorsal line and the lateral line
  • injection into the dorso-median sinus e.g. an injection in the mid-dorsal line in the angle at the caudal margin of the cranial dorsal fin.
  • compositions suitable for parenteral administration comprise solutions in a solvent having solubility for Modoflaner, such as glycofurol (tetraglycol), acetone, acetonitrile, benzyl alcohol, butyl diglycol, dimethylacetamide, dimethylsulfoxide, dimethylformamide (DMF), N,N-diethyl-3-methylbenzamide, dipropylene glycol n-butyl ether, ethyl alcohol, isopropanol, methanol, phenylethyl alcohol, isopropanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethylaceamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycols, propylene glycol, N-methylpyrrolidone (NMP), 2-pyrrolidone, limonene, eucalyptol, diethylene glycol monoethyl ether, ethylene glycol, diethyl phthalate,
  • the dose of Modoflaner ranges from about 0.1 mg/kg to 150 mg/kg, preferably from 10 mg/kg to about 150 mg/kg, more preferably from about 10 mg/kg to about 120 mg/kg, even more preferably from 60 to 120 mg/kg, of the fish bodyweight.
  • the dose of Modoflaner to administer depends on several factors, including notably the parasite and the sought duration of activity.
  • the dose of Modoflaner is about 30 mg/kg, about 40 mg/kg, about 50 mg/kg, about 60 mg/kg, about 70 mg/kg, about 80 mg/kg, about 90 mg/kg, about 100 mg/kg, about 110 mg/kg, about 120 mg/kg, about 130 mg/kg, about 140 mg/kg or about 150 mg/kg.
  • Modoflaner is administered by parenteral administration, in particular by intraperitoneal injection or intramuscular injection.
  • the dose administered parenterally is comprised between 60 and 120 mg/kg.
  • the dose of Modoflaner is 90 mg/kg.
  • Modoflaner may be administered subcutaneously, intramuscularly or intraperitoneally to the salmon as an implant comprising Modoflaner and a biodegradable polymer, such as poly(lactic-co-glycolic acid) (PLGA)- and/or poly(lactic acid) (PLA)-based implant, in particular as poly(lactic-co-glycolic acid) (PLGA)- and/or poly(lactic acid) (PLA)-based microspheres.
  • PLGA poly(lactic-co-glycolic acid)
  • PLA poly(lactic acid)-based microspheres
  • Modoflaner may be administered at any time during the life of the fish, either prophylactically (e.g. to prevent the infestation by parasites) or therapeutically (e.g. to treat an already existing parasitic infestation).
  • Modoflaner is preferably administered prophylactically to smolts, before the smolts are transferred from fresh-water tanks or cages to sea water cages and may enter in contact with the parasite.
  • the smolts weight between 50 and 350 g, preferably 50 and 150 g, more preferably between 80 and 120 g.
  • Modoflaner is well-tolerated by the smolts at doses as high as 120 mg/kg. In addition, this dose provides protection against parasites for at least four months despite the important weight gain of the salmon during this period of about tenfold.
  • a single dose of Modoflaner is sufficient to control a parasite infestation for at least 4 months, 5 months or 6 months.
  • a single dose of 90 mg/kg to 120 mg/kg of Modoflaner is sufficient to control a parasite infestation for at least 4 months, 5 months or 6 months.
  • Modoflaner provides a reduction or maintenance of the number (or count) of gravid (or ovigerous) female sea lice or adult sea lice below a regulatory threshold, i.e. a count of sea lice over which a treatment must be administered.
  • thresholds are 0.1 gravid female / fish during outmigration period of wild salmon (ASC), 0.2 gravid female / fish during outmigration period of wild salmon and 0.5 gravid female / fish during the rest of the year (Norway), 0.3-0.5 gravid female / fish during outmigration period of wild salmon and 2.0 gravid female / fish during the rest of the year (Ireland), 1.5 gravid female / fish (Faroe Islands), 3.0 gravid female / fish (Chile and Scotland), 3.0 adult sea lice (British Columbia, Canada).
  • the second aspect also encompasses the use of Modoflaner for controlling a parasite infestation on a fish, as described above.
  • the second aspect also encompasses also a method of controlling a parasite infestation on a fish as described above, which comprises administering to the fish an effective dose of Modoflaner, as described above.
  • the second aspect further encompasses the use of Modoflaner for the manufacture of a medicament intended for controlling a parasite infestation on a fish, as described above.
  • the present invention concerns a method of controlling a sea lice infestation in a farmed Salmonidae comprising administering intraperitoneally or intramuscularly to the fish a pharmaceutical active ingredient selected from the group consisting in Modoflaner and an isoxazoline, preferably lotilaner, afoxolaner, sarolaner or fluralaner, or a pharmaceutical composition comprising a pharmaceutical active ingredient selected from the group consisting in Modoflaner and an isoxazoline, preferably lotilaner, afoxolaner, sarolaner or fluralaner, and one or more pharmaceutical excipients.
  • the frequency of administration to the fish is reduced.
  • the parenteral route of administration of the pharmaceutical active ingredient has a limited environmental impact, notably on the surrounding ecosystems and wild fish when compared to the currently used routes of administration as bath or feed.
  • the farmed Salmonidae is selected from the group consisting in Atlantic salmon (Salmo salar), Coho salmon (Oncorhynchus kisutch), Chinook salmon (Oncorhynchus tshawytscha) and rainbow trout (Oncorhynchus mykiss), notably Atlantic salmon ( Salmo salar ).
  • the pharmaceutical active ingredient is Modoflaner.
  • the dose of Modoflaner ranges from about 0.1 mg/kg to 150 mg/kg, preferably from 1 mg/kg to about 100 mg/kg, more preferably from about 10 mg/kg to about 90 mg/kg, even more preferably from 30 to 50 mg/kg, of the fish bodyweight.
  • the dose of Modoflaner is 30 mg/kg or 40 mg/kg.
  • the dose of Modoflaner is about 30 mg/kg, about 40 mg/kg, about 50 mg/kg, about 60 mg/kg, about 70 mg/kg, about 80 mg/kg, about 90 mg/kg, about 100 mg/kg, about 1100 mg/kg, about 120 mg/kg, about 130 mg/kg, about 140 mg/kg or about 150 mg/kg.
  • the dose of Modoflaner administered parenterally is comprised between 60 and 120 mg/kg. In one particular embodiment, the dose of Modoflaner is 90 mg/kg.
  • the isoxazoline is fluralaner.
  • the dose of fluralaner ranges from 1 to 100 or 120 mg/kg, preferably from 10 to 90 mg/kg, more preferably from 25 to 50 mg/kg, or from about 40 mg/kg to about 120 mg/kg, of fish bodyweight, more particularly about 40 mg/kg, of fish bodyweight.
  • the pharmaceutical active ingredient or the pharmaceutical composition is administered to juvenile fish, in particular to smolts, said juvenile fish or smolt having a weight ranging from 50 to 350 grams, preferably from 50 to 150 g, more preferably ranging from 80 to 120 g.
  • the sea lice is selected from the group consisting in Lepeophtheirus salmonis, Caligus clemensi, Caligus curtus, Caligus dussumieri, Caligus elongates, Caligus longicaudatus, Caligus rogercresseyi or Caligus stromii, more particularly Lepeophtheirus salmonis or Caligus rogercresseyi, or combinations thereof.
  • the sea lice is selected from haematophagous sea lice, for example Lepeophtheirus salmonis .
  • the sea lice is selected from haematophagous sea lice, for example Lepeophtheirus salmonis
  • the fish is selected from the group consisting in Atlantic salmon ( Salmo salar ), Coho salmon ( Oncorhynchus kisutch ), Chinook salmon ( Oncorhynchus tshawytscha ) and rainbow trout ( Oncorhynchus mykiss ), notably Atlantic salmon ( Salmo salar ).
  • the method of controlling a sea lice infestation in a farmed Salmonidae comprises administering intraperitoneally or intramuscularly to the fish a pharmaceutical active ingredient selected from the group consisting in Modoflaner and an isoxazoline, preferably lotilaner, afoxolaner, sarolaner or fluralaner, or a pharmaceutical composition comprising a pharmaceutical active ingredient selected from the group consisting in Modoflaner and an isoxazoline, preferably lotilaner, afoxolaner, sarolaner or fluralaner, and one or more pharmaceutical excipients to a juvenile fish, in particulars to smolts for the initial treatment and thereafter every 3, 4, 5 or 6 months to the fishes collected in sea water cages.
  • the third aspect also encompasses the use of a pharmaceutical active ingredient selected from the group consisting in Modoflaner and an isoxazoline, preferably lotilaner, afoxolaner, sarolaner or fluralaner, or a pharmaceutical composition comprising a pharmaceutical active ingredient selected from the group consisting in Modoflaner and an isoxazoline, preferably lotilaner, afoxolaner, sarolaner or fluralaner, and one or more pharmaceutical excipients for controlling a sea lice infestation in a farmed Salmonidae, wherein the pharmaceutical active ingredient or pharmaceutical composition is administered intraperitoneally or intramuscularly to the farmed Salmonidae, as described above.
  • the third aspect also encompasses a pharmaceutical active ingredient selected from the group consisting in Modoflaner and an isoxazoline, preferably lotilaner, afoxolaner, sarolaner or fluralaner, or a pharmaceutical composition comprising a pharmaceutical active ingredient selected from the group consisting in Modoflaner and an isoxazoline, preferably lotilaner, afoxolaner, sarolaner or fluralaner, and one or more pharmaceutical excipients for use in controlling a sea lice infestation in a farmed Salmonidae, wherein the pharmaceutical active ingredient or pharmaceutical composition is administered intraperitoneally or intramuscularly to the farmed Salmonidae, as described above.
  • the third aspect further encompasses the use of a pharmaceutical active ingredient selected from the group consisting in Modoflaner and an isoxazoline, preferably lotilaner, afoxolaner, sarolaner or fluralaner, or a pharmaceutical composition comprising a pharmaceutical active ingredient selected from the group consisting in Modoflaner and an isoxazoline, preferably lotilaner, afoxolaner, sarolaner or fluralaner, and one or more pharmaceutical excipients for the manufacture of a medicament intended for intraperitoneal or intramuscular administration, for controlling a parasite infestation on a fish, as described above.
  • the present invention concerns Modoflaner for use in controlling a Lepeophtheirus salmonis, Caligus elongates or Caligus rogercresseyi infestation in a Salmonidae, preferably Atlantic salmon ( Salmo salar ), Coho salmon ( Oncorhynchus kisutch ), Chinook salmon ( Oncorhynchus tshawytscha ) or a trout, in particular rainbow trout ( Oncorhynchus mykiss ), wherein a dose of Modoflaner ranging from about 60 to about 120 mg/kg, notably about 90 mg/kg or about 120 mg/kg; of fish bodyweight is administered parenterally, in particular intraperitoneally, to the Salmonidae, said dose providing control of the infestation for at least 4 months, or more than 4 months, 5 months or 6 months.
  • a Salmonidae preferably Atlantic salmon ( Salmo salar ), Coho salmon ( Oncorhynchus kisutch ), Chinook salmon
  • Example 1 evaluation of the efficacy of Modoflaner in treating a sea lice infestation
  • Atlantic salmon (Salmo salar), of about 350g, were sea lice-infested (infection dose of 20 copepodids/fish, Lepeophtheirus salmonis ), 4 weeks prior to the D0 injection described above.
  • the fish were kept in sea water at ambient temperature (about 11 °C), 32 ⁇ average salinity. Fish were fed with automatic feeders.
  • the number of lice at the time of injection (D0) was about 11.1 lice per fish.
  • Modoflaner was injected at D0 in two doses (10 mg/kg and 30 mg/kg), as depicted in Table 1: Group n (number of fish) Dose (mg/kg) Formulation Dose volume (mL/fish) Dosing route T1 20 10 2% solution in DMSO 0.1 IP (intraperitoneal) T2 20 30 6% solution in DMSO 0.1 IP (intraperitoneal) C 20 - DMSO 0.1 IP (intraperitoneal)
  • the number of sea lice in each group was evaluated after 7 days and 14 days.
  • the average number of sea lice in the control group was 9.2 lice / fish and 7.2 lice / fish, respectively.
  • the average number of sea lice was 0.05 lice / fish at 7 days and 0 at 14 days.
  • Modoflaner is effective in treating a sea lice infestation after 7 days at a dose as low as 10 mg/kg when administered intraperitoneally.
  • Example 2 evaluation of the efficacy of Modoflaner in preventing a Sea lice infestation.
  • the efficacy corresponds to the reduction of the mean lice number obtained with Modoflaner in the T1-T3 groups, compared to the C group.
  • Example 3 Efficacy and Safety of fluralaner and modoflaner against sea lice (Lepeophtheirus salmonis) infestations in farmed salmon in natural sea conditions in Norway.
  • the fish were Atlantic salmon (smolts, 500 to 1000 individuals per cage, 3 cages per group) having an average weight at start of 100 g.
  • the fish were vaccinated with conventional vaccine: ALPHA JECT micro 7 from Pharmaq, dose size 0.05 ml injected intraperitoneally.
  • the fish were removed from the unit and put in a container with water added anesthetic (Finquel Vet) before the fish was individually weighed and treated (by injection of product). After treatment the fish was placed in a container with water before they were moved back into their respective trial unit.
  • anesthetic Ferquel Vet
  • the fish were then transferred from Land tanks to R&D Sea. First all fish were individually weighed and injected with the products at R&D Land at a bodyweight between 150 and 200 g and thereafter transferred to R&D Sea within two-three week after weighing. Arriving at R&D Sea the fish were placed in units based on treatment group.
  • the fish were transferred from the sea unit to land containers, one fish per container, and lice that has fallen of each fish were counted. In addition to sea lice counting the fish were weighed, opened and scored by Speilberg scale. No fish or lice was stored after sampling. Fish are maintained in the study units at R&D Sea and identified by unit number until the end of the trial. All remaining fish after trial termination will be euthanized.
  • Delousing Any unit may be subject for delousing if the threshold of 1 adult female per fish in average is reached in the study unit or for animal welfare reason. If the threshold was reached for 2 consecutive samplings all units in the same group were subjected to delousing. All fish were sedated before the lice removed mechanically by point suction on each individual fish. The lice were not stored after counting.
  • the dose of 90 mg/kg of fish resulted in more than 6 months control, at an average of less than 0.5 sea lice per fish.
  • Fluralaner, administered at the dose of 40 mg/kg of fish provided a lesser control and delousing was required at 4 months.
  • both fluralaner at 40 mg/kg of fish and modoflaner at 90 mg/kg of fish administered parenterally provide control of Lepeophtheirus salmonis infestation in sea. Both investigational products were well tolerated.
  • Example 4 Long-term product efficacy trial against sea lice (Caligus rogercresseyi) infestation upon Atlantic salmon (Salmo salar).
  • the objective of the study is to evaluate the efficacy of two experimental injectable products against C. rogercresseyi at chalimus and adult stages on Atlantic post-smolts salmons at 3 and 6-months post application.
  • the investigational products were evaluated against a negative control (0.9% NaCl solution), a positive control (NMP).
  • the investigational products were either fluralaner (solution in NMP) administered at the 40 mg/kg dose or modoflaner (solution in NMP) administered at 90 mg/kg or 120 mg/kg of fish.
  • the fish (646 individuals) was Atlantic salmon (Salmo salar), post-smolts (strain Stofnfiskur). Fish size were ⁇ 60 g at stocking, ⁇ 130 g at injection of control product and ⁇ 180 g at injection of test products. All fish was vaccinated on stocking day with BlueGuard®5-1.
  • test fish were stocked in a hatchery and vaccinated with BlueGuard® 5.1.
  • fish (n: 1200) were anaesthetised in groups of ⁇ 25 then intraperitoneally vaccinated with 0.1 ml of the vaccine.
  • Fish were left to acclimate and immunize for 126 days until proper smoltification. Then, all fish were transferred to a 4000 L tanks to complete their acclimation and immunization periods before injection of the test / control products.
  • test fish were marked, weighed, and injected with the test / positive control product. All fish were starved for 48 hours prior to the handling. Then, and in groups of ⁇ 20 fish at a time, they were anaesthetized and then injected with the corresponding test / control product (0.1 ml intraperitoneally).
  • the Study involved the performance of 3 sea lice challenges after 90 and 180 days (3 and 6 months) according to the following schedule: Challenge n° Study day Number of tanks Number of replicas Number of fish per group per replica Caligus stage counted 1 90 4 2 20-10 Adult 2 180 2 2 10-5 Adult

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne Modoflaner, un composé arylaminobenzamide, pour son utilisation dans la lutte contre une infestation parasitaire chez un poisson et une isoxazoline pour son utilisation dans la lutte contre une infestation parasitaire chez un poisson, ladite isoxazoline étant administrée par voie parentérale.
PCT/EP2024/056706 2023-03-13 2024-03-13 Composés d'arylaminobenzamide ou d'isoxazoline destinés à être utilisés dans la lutte contre une infestation parasitaire chez un poisson Pending WO2024189101A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP23305337 2023-03-13
EP23305337.0 2023-03-13

Publications (1)

Publication Number Publication Date
WO2024189101A1 true WO2024189101A1 (fr) 2024-09-19

Family

ID=85778769

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2024/056706 Pending WO2024189101A1 (fr) 2023-03-13 2024-03-13 Composés d'arylaminobenzamide ou d'isoxazoline destinés à être utilisés dans la lutte contre une infestation parasitaire chez un poisson

Country Status (1)

Country Link
WO (1) WO2024189101A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016042154A1 (fr) 2014-09-19 2016-03-24 Pharmaq As Formulation
WO2017021498A1 (fr) 2015-08-05 2017-02-09 Pharmaq As Agent de lutte contre les parasites des poissons
WO2019059412A1 (fr) 2017-09-20 2019-03-28 Mitsui Chemicals Agro, Inc. Agent de lutte prolongée contre les ectoparasites pour un animal
WO2022101502A1 (fr) 2020-11-16 2022-05-19 Virbac Comprimé comprenant du modoflaner comme principe actif
WO2022226660A1 (fr) * 2021-04-30 2022-11-03 Ohalloran John Utilisation d'isoxazoline pour protéger des poissons contre des parasites

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016042154A1 (fr) 2014-09-19 2016-03-24 Pharmaq As Formulation
WO2017021498A1 (fr) 2015-08-05 2017-02-09 Pharmaq As Agent de lutte contre les parasites des poissons
WO2019059412A1 (fr) 2017-09-20 2019-03-28 Mitsui Chemicals Agro, Inc. Agent de lutte prolongée contre les ectoparasites pour un animal
WO2022101502A1 (fr) 2020-11-16 2022-05-19 Virbac Comprimé comprenant du modoflaner comme principe actif
WO2022226660A1 (fr) * 2021-04-30 2022-11-03 Ohalloran John Utilisation d'isoxazoline pour protéger des poissons contre des parasites

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ZHOU XUEYING ET AL: "Current review of isoxazoline ectoparasiticides used in veterinary medicine", vol. 45, no. 1, 17 March 2021 (2021-03-17), GB, pages 1 - 15, XP093067662, ISSN: 0140-7783, Retrieved from the Internet <URL:https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jvp.12959> [retrieved on 20230726], DOI: 10.1111/jvp.12959 *

Similar Documents

Publication Publication Date Title
US5439924A (en) Systemic control of parasites
WO2022226660A1 (fr) Utilisation d&#39;isoxazoline pour protéger des poissons contre des parasites
EP0353526B1 (fr) Agent renfermant des dérivés de la triazindione contre les parasites
US6982285B2 (en) Control of parasites attached to skin of fish
DK202370418A1 (en) Cyclopropylamide compounds against parasites in fish
JP3170077B2 (ja) 寄生生物の全身的駆除
WO2024189101A1 (fr) Composés d&#39;arylaminobenzamide ou d&#39;isoxazoline destinés à être utilisés dans la lutte contre une infestation parasitaire chez un poisson
EP2310017A1 (fr) Nifurtimox pour le traitement de maladies provoquées par les trichomonadida
US8128943B2 (en) Use of oxazole derivatives for controlling fish parasites
US10765657B2 (en) Selamectin for treatment of sea lice infestations
CN107920531B (zh) 用于对抗鱼类寄生虫的试剂
CA3103102C (fr) Utilisation d&#39;oxime de milbemycine contre les poux de mer sur les poissons
CN101495107A (zh) 鱼类体表寄生虫驱除方法
JP2023078111A (ja) グルタルアルデヒドを含む魚類寄生虫駆除剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24710430

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2024710430

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2024710430

Country of ref document: EP

Effective date: 20251013

ENP Entry into the national phase

Ref document number: 2024710430

Country of ref document: EP

Effective date: 20251013

ENP Entry into the national phase

Ref document number: 2024710430

Country of ref document: EP

Effective date: 20251013

ENP Entry into the national phase

Ref document number: 2024710430

Country of ref document: EP

Effective date: 20251013

ENP Entry into the national phase

Ref document number: 2024710430

Country of ref document: EP

Effective date: 20251013