Classifications

• • 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
  • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
  • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
  • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
  • A01N47/34—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the groups, e.g. biuret; Thio analogues thereof; Urea-aldehyde condensation products
• • 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
  • A61K31/16—Amides, e.g. hydroxamic acids
  • A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
• • 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
  • A61P33/10—Anthelmintics
  • A61P33/12—Schistosomicides

Definitions

• the present invention relates to compositions for the systematic control of warm-blooded animal parasites 5 comprising an effective quantity of a particular aryl- benzoylurea.
• the present invention relates to compositions comprising an effective quantity of l-[3-chloro-4- (1,1, 2-trifluoro-2-trifluoromethoxyetho- 10 xy) phenyl] -3- (2 , 6-difluorobenzoyl) urea and a pharmaceutically acceptable carrier and their use for the systematic control of warm-blooded animal parasites.
• the present invention also relates to the use of 1- [ 3-chloro-4- (1,1, 2-trifluoro-2-trifluoromethoxyetho- 15 xy) phenyl] -3- (2 , 6-difluorobenzoyl) urea as such for the systemic control of warm-blooded animal parasites.
• European patent EP 271.923 describes the compound corresponding to l-[3-chloro-4- (1, 1, 2-trifluoro-2-tri- fluoro ethoxyethoxy) phenyl ] -3- (2 , 6-difluorobenzoyl) urea having formula ( i;
• the above patent also discloses a method for fighting infestations caused by harmful insects which consists in distributing the compound having formula (I) , as such or in the form of a suitable composition, onto the surface of the infested area.
• This method of application is effective for the treatment of agricultural cultivations, basins and waterways, industrial and civil sites, but its utility is limited if the compound having formula (I) is to be adopted in the veterinary and zootechnical field, for example, for protecting domestic animals from these parasites which feed by sucking their host's blood, such as flees, ticks, louse, etc.
• the compound having formula (I) is surprisingly effective in protecting warm-blooded animals from ectoparasites and endoparasites, if it is systemically carried into the blood of the animal host as such or, preferably, by means of a suitable pharmaceutically acceptable compo- s ition .
• the compound having formula (I) has a very low oral toxici- ty, both acute and chronic, on mammels and birds, it does not have mutagen and tetragen effects and does not have the tendency to accumulate in adipose tissues, the use of this compound having formula (I) , as well as being particularly effective, is also safe and harmless for the animals treated.
• compositions comprising an effective quantity of l-[3-chlo- ro-4- (1,1, -trifluoro-2-trifluoromethoxyethoxy) phenyl ] 3- (2 , 6-difluorobenzoyl) rea having formula (I):
• compositions can be used for the syste - ic control of warm-blooded animal parasites.
• the compound having formula (I) can be prepared by means of a process which comprises the reaction of 3-chloro-4- (1,1, 2-trifluoro-2-trifluoromethoxyethoxy) - aniline having formula ( II ) :
• the compound having formula (I) can be prepared by a process which comprises the reaction of 3-chloro-4- (1,1, 2-trifluoro-2-trifluoromethoxyethoxy) phenylisocyanate having formula (IV):
• inert solvents suitable for the purpose are aromatic hydrocarbons such as, for example, benzene, toluene, xylene, chlorobenzene; chlorinated hydrocarbons such as, for example, methylene chloride, chloroform, carbon tetrachloride, dichloroethane; ethers such as, for example, diisopropylether, tetrahy- drofuran, dioxane.
• the compounds having formula (III) and (V) can be prepared according to methods which are well known in literature.
• the compound having formula (V) is also commercially available.
• the compound having formula (II) can be prepared as described, for example, in European patent EP 2-71.923.
• the compound having formula (IV) can be prepared starting from the compound having formula (II) and phosgene, operating according to an analogous procedure to that described, for example, by Blatt in: "Organic Synthesis” (1959), Collective Vol. 2, pages 453-455, John Wiley Ed. , New York.
• Carriers which can be used for the purposes of the present invention can be liquids or solids according to the method of administration.
• the above compositions can be administered in any form which allows them to be introduced into the blood of the animal to be protected such as, for example, orally or by percutaneous administration.
• Carriers which are suitable for the purpose are those which do not have harmful effects on the animals to be treated and which do not negatively influence the method of application or the desired results.
• liquid carriers which can be used for the purposes of the present invention are: water, N-methylpyrrolidone, vegetable oil, glycols, etc.
• solid carriers which can be used for the present invention are: talc, clay, molasses in powder form, cellulose and its derivatives, lactose, starch, colloidal silica, magnesium stearate, stearic acid, etc.
• the compound having formula (I) can also be administered to the animals to be treated as such.
• the oral administration can be carried out by mixing the compound having formula (I) , as such or formulated with a suitable carrier, in the food or drinking water, or administering it in the form of long drinks, tablets, capsules, etc.
• This formulation can be, for example, a concentrated suspension which is mixed with the water or a dry preparation which is mixed and suspended in the water. In both cases, it is preferable to have the compound having formula (I) in a finely pulverized form.
• the compound having formula (I) can be easily formulated into capsules or tablets, according to the methods traditionally used in pharmaceutical practice.
• Gelatine capsules contain the active principle (com- pound having formula (I) , in the present case) and solid carriers such as, for example, colloidal silica, lactose, starch, derivatives of cellulose, magnesium stearate, stearic acid and the like. These carriers can also be used to make tablets.
• Both tablets and capsules can be produced as drugs with controlled release in order to provide a continuous release of the active principle for a certain period, for example, several hours .
• the percutaneous administration can be conve- niently carried out by means of subcutaneous, dermal, intermuscular or intravenous injection according to the methods normally used in pharmaceutical and veterinary practice.
• the percutaneous administration can also be carried out by absorption of the compound having formula (I) through the epidermis of the animal to be treated. This absorption takes place as a result of surface treatment of the animal to be treated by immersion, wetting, spraying, powdering, smearing, etc.
• an injectable suspension can be conveniently prepared by suspending the compound having formula (I) , in the form of fine powder, in a formulation of pharmaceutically acceptable liquid carriers.
• Liquid carriers which can be used for the purpose are, for example, vegetable oils such as peanut oil, corn oil, etc; glycols such as polyethylene glycols, etc; water, etc.
• emulsifying agents such as, for example, emulsifying agents, suspending agents, disper- sers, thickners, surface-active agents, etc.
• emulsifying agents which can be used for the purpose are: salts of dodecylbenzenesulfonate and toluenesulfonate, adducts of ethylene oxide and
• esters of oleic acid or stearic acid etc.
• dispersers which can be used for the purpose are: salts of naphthalenesulfonate, lignin sulfonate, sulfates of fatty alcohols, etc.
• thickners which can be used for the purpose are: carboxymethylcellulose, polyvinylpyrrol- idone, gelatine, alginates, etc.
• Examples of surface-active agents which can be used are: lecithin, esters of polyoxyethylene sorbitan, etc.
• compositions of the present invention can contain, as well as the compound having formula (I) , other antiparasitic agents such as, for example, other insecticides, acaricides, anthelminthics, etc.
• insecticides and/or acaricides which can be used for the purposes of the present invention are: chlorpyrifos, coumaphos, dichlorvos, diazinon, dimethoate, fenthion, malathion and other phosphorganic products; lindane, nicotine, rotenone, natural pyretri- nes and synthetic pyretroids; avermectine, milbemicine and their derivatives, fenoxycarb, pyriproxyfen, diofenolan, l-(5-chloro-4-pentinyloxy) -4-phenoxybenzene and other products with a young hormone activity; imidacloprid, acetamiprid, nitenpyram, fipronil.
• compositions of the present invention can contain, in addition to the compound having formula (I), other biologically active substances such as, for example, medicines, growth promoters, vitamins, mineral salts, etc.
• compositions of the present invention or the compound having formula (I) as such are the following: mites belonging to the suborders Mesostigmata,
• Sarcoptiformes, Trombidiformes and Onchychopalpi- da - louse belonging to the orders Anoplura and Mal- lophaga; ticks belonging to the Ixodidae and Argasidae families; flees belonging to the Pulicidae and Ceratophylli- dae families; bugs of various types;
• Triatoma and other Heteroptera diptera belonging to the suborders Brackycera
• Warm-blooded animals which can be treated using the compositions of the present invention or the compound having formula (I) as such are, apart from human beings, domestic animals such as cattle, horses, sheep, goats, poultry, pigs, dogs and cats.
• the present invention also relates to the use of the above compositions for the systemic control of warm-blooded animals.
• the dosage of the compound having formula (I) can vary depending on various factors such as the means of administration, the type and degree of infestation, the age, state of health, body weight of the animal to be treated, the frequency of the treatment, desired effects. Dosages of the compound having formula (I) generally between 0.01 mg and 1000 mg per kg of the body weight of the animal to be treated, preferably between 0.1 mg and 100 mg per kg of body weight, are sufficient to eradicate the parasites without prejudicing the health of the animals treated. Some illustrative examples are provided for a better understanding of the invention and for its embodiment, but do not restrict the scope of the invention in any way.
• EXAMPLE 1 Preparationof 3-chloro-4- (l,l,2-trifluoro-2-trifluoro- methoxyethoxy) aniline having formula (II).
• Perfluoromethylvinylether (1.66 g, 10 mmoles) , in a mixture consisting of 2-chloro-4-aminophenol (1.44 g, 10 mmoles) , di ethylsulfoxide (20 ml) , toluene (20 ml) and potassium carbonate in powder form at 85% (100 mg) is bubbled into a 100 ml flask, under nitrogen, at 0°C.
• a solid mixture is prepared consisting of Compound (I), obtained as described in Example 2, and clay in the following weight percentages: 5% of Compound (I) ; 95% of clay.
• Formulation of Compound (I) in tablet-form Following the conventional procedures, tablets are prepared each containing Compound (I) in a finely pulverized form (100 mg) , colloidal silica (0.2 mg) , magnesium stearate (5 mg) , microcrystalline cellulose (275 mg) , starch (11 mg) and lactose (98.8 mg) . Tablets containing dosages of between 20 mg and 200 mg of active principle can be analogously prepared.
• EXAMPLE 5 Preparation of Compound (I) in gelatine capsules.
• Standard capsules consisting of two parts of hard gelatine, are filled with a mixture of lactose (150 mg) , cellulose (50 mg) , magnesium stearate (6 mg) and Compound (I) in a finely pulverized form (25 mg) .
• One group (Cl and C2) is treated for 10 consecutive days with a daily dosage of 5 mg/kg of body weight of Compound (I) , administered orally by the addition to the daily diet of the composition obtained as described in Example 3.
• the second group of dogs (C3 and C4) is used as a control and is fed with the same diet as the first group but without the addition of Compound (I) .
• the eggs of the flees used for the infestation are collected on sheets of paper placed under the cages where the dogs are kept for the whole duration of the treatment.
• the eggs are counted, placed on an artificial culture me- dium and incubated. The number of pupae and adults of flees which emerge is determined and indicated in Table 1.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• General Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• Public Health (AREA)
• Plant Pathology (AREA)
• Tropical Medicine & Parasitology (AREA)
• Pest Control & Pesticides (AREA)
• Epidemiology (AREA)
• Engineering & Computer Science (AREA)
• Dentistry (AREA)
• Wood Science & Technology (AREA)
• Zoology (AREA)
• Environmental Sciences (AREA)
• Agronomy & Crop Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Agricultural Chemicals And Associated Chemicals (AREA)
• Medicinal Preparation (AREA)

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Cited By (12)

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Citations (5)

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• 1996
  • 1996-12-12 IT IT96MI002602A patent/IT1290845B1/it active IP Right Grant
• 1997
  • 1997-12-09 ES ES97954387T patent/ES2181056T3/es not_active Expired - Lifetime
  • 1997-12-09 AU AU58561/98A patent/AU727536B2/en not_active Expired
  • 1997-12-09 JP JP52623698A patent/JP4495256B2/ja not_active Expired - Lifetime
  • 1997-12-09 US US09/319,261 patent/US6136836A/en not_active Expired - Lifetime
  • 1997-12-09 DE DE69715657T patent/DE69715657T2/de not_active Expired - Lifetime
  • 1997-12-09 WO PCT/EP1997/006965 patent/WO1998025466A1/en not_active Ceased
  • 1997-12-09 EP EP97954387A patent/EP0944321B1/en not_active Expired - Lifetime
  • 1997-12-09 CA CA002274556A patent/CA2274556C/en not_active Expired - Lifetime
  • 1997-12-09 NZ NZ336252A patent/NZ336252A/xx not_active IP Right Cessation
  • 1997-12-09 AT AT97954387T patent/ATE224139T1/de active

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