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
  • A61K31/4164—1,3-Diazoles
  • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
• • 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
  • A61K31/4196—1,2,4-Triazoles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P33/00—Antiparasitic agents
  • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis

Definitions

• the present invention relates to the combined use of substituted benzimidazoles and of 1,2,4-triazine compounds against parasitic protozoa, in particular coccidia.
• Substituted benzimidazoles and . their use as insecticides, fungicides and herbicides has already become known (EP-OS 87 375, 152 360, 181 826, 239 508, 260 744, 266 984, US-P 3 418 318, 3 472 865, 3 576 818, 3 728 994).
• Halogenated benzimidazoles and their action as anthelmintics, coccidiostats and pesticides have become known (DE-OS 2,047,369, EP 597 304 Al).
• the substituted benzimidazoles preferably used according to this invention are described in WO 00/04022 and WO 00/68225.
• coccidiosis An important example of a disease caused by unicellular parasites (protozoa) is coccidiosis. It can cause large losses, especially in poultry rearing. To avoid this, the stocks are treated prophylactically with Coccidioseschn. The development of resistance to the funds used leads to serious problems shortly after the funds are introduced. On the other hand, the use of completely new coccidiosis agents, in particular combinations, makes it possible to control polyresistant parasite strains.
• the invention therefore relates to:
• Products containing in each case at least one active against parasitic protozoa substituted benzimidazole and 1,2,4-triazine derivative containing in each case at least one active against parasitic protozoa substituted benzimidazole and 1,2,4-triazine derivative.
• Preferred benzimidazoles are those of the formula (I)
• Z is hydrogen or the radical -CHR 2 R 3 ,
• R 1 is fluoroalkyl
• R 2 is hydrogen or alkyl
• R 3 is a radical of the formula
• R 4 is alkyl
• R 5 is alkyl or substituted phenyl
• R 6 is alkyl
• X 2 , X 3 and X 4 independently of one another represent hydrogen, halogen, haloalkyl, haloalkoxy, haloalkylthio or haloalkylsulfonyl,
• X 2 and X 3 or X 3 and X 4 together represent a dioxyhaloalkylene radical.
• the substituted benzimidazoles according to the invention are generally defined by the formula (I).
• R! is preferably C 1 -C 4 -fluoroalkyl
• R 2 is preferably hydrogen or C 1 -C 4 -alkyl
• R.4 is preferably C 1 -C 4 -alkyl
• R-> is preferably Ci- ⁇ -alkyl or phenyl, which is optionally mono- or polysubstituted substitu ⁇ ated with Ci- 4 alkyl, d- 4 haloalkyl, halo, nitro, Ci -4 alkoxy, Q ⁇ - Haloalkoxy or optionally one or more times halogen-substituted methylene or ethylenedioxy.
• R 6 is preferably C 1-4 -alkyl
• ⁇ l, X ⁇ , ⁇ 3 and X ⁇ are preferably each independently hydrogen, F, Cl, Br, C 1 -C 4 -haloalkyl, C 1 -C 4 -haloalkoxy, C 1 -C 4 -haloalkylthio, C 1 -C 4 -halogenoalkylsulfonyl, or
• X.sup.1 and X.sup.2 or X.sup.1 and X.sup.2 together represent, according to a further preferred embodiment, a dioxyhalo-C 1 -C 4 -alkylene radical.
• R 1 particularly preferably stands for CF3, CHF2 or CHF.
• R 1 particularly preferably represents hydrogen, methyl, ethyl, n-propyl or isopropyl.
• R4 particularly preferably represents methyl, ethyl, n-propyl or isopropyl.
• R5 is particularly preferably Ci -6 alkyl.
• R ⁇ is particularly preferably methyl or ethyl.
• ⁇ l, X ⁇ , X ⁇ and X ⁇ are more preferably independently of one another hydrogen, F, Cl, Br, CF 3 , CHF 2 , CH 2 F, OCF 3 , OCH 2 F, OCHF 2 , SCF 3 , SCHF 2 , SCH 2 F, SO 2 CF 3 , SO 2 CHF 2 , SO 2 CH 2 F.
• R-> is a radical of the formula
• K? for a remainder of the formula
• RI very particularly preferably represents -CF3.
• R ⁇ is very particularly preferably hydrogen.
• R4 is very particularly preferably methyl.
• X * is most preferably Cl or Br.
• X 1 is very particularly preferably hydrogen.
• XP and X ⁇ together are -OCF2-CF2-O-.
• Alkyl is a straight-chain or branched hydrocarbon radical having 1 to 8, preferably 1 to 6, particularly preferably 1 to 4 carbon atoms, such as. Methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl.
• Alkylene represents a straight-chain or branched hydrocarbon radical having 1 to 4, preferably 1 to 3, particularly preferably 1 to 2, carbon atoms which is linked via two different positions.
• Haloalkyl is an alkyl radical as defined above in which one or more, in particular 1 to 3, hydrogen atoms have been replaced by a halogen atom, in particular fluorine, chlorine or bromine. Accordingly, fluoroalkyl represents an alkyl group in which 1 until all hydrogens have been replaced by fluorine atoms; Preference is given to perfluoroalkyl radicals, for example trifluoromethyl or pentafluoroethyl.
• Haloalkoxy represents a straight-chain or branched alkoxy radical having 1 to 8, preferably 1 to 6, particularly preferably 1 to 4, carbon atoms in which one or more, in particular 1 to 3, hydrogen atoms have been replaced by a halogen atom, in particular fluorine, chlorine or bromine; eg -OCF 3 .
• Haloalkylthio is a straight-chain or branched alkylthio radical having 1 to 8, preferably 1 to 6, more preferably 1 to 4, carbon atoms in which one or more, in particular 1 to 3, hydrogen atoms are replaced by a halogen atom, in particular fluorine, chlorine or bromine were replaced; eg CF 3 S-.
• Haloalkylsulfonyl is a straight-chain or branched alkylsulfonyl radical having 1 to 8, preferably 1 to 6, particularly preferably 1 to 4 carbon atoms, in the alkyl part of which one or more, in particular 1 to 3, hydrogen atoms have been replaced by a halogen atom, in particular fluorine, chlorine or bromine.
• Z in formula (I) is hydrogen and the other substituents may have the meanings given above, including the preferred and particularly preferred meanings.
• the compound of the formula (I-A) (see WO00 / 04022) may be mentioned:
• Z in formula Q) is the radical -CHR 2 R 3 and the other substituents may have the meanings given above, including the preferred and particularly preferred meanings.
• Preferred examples of this embodiment are the compound of the formula (IB) (see WO00 / 04022) and in particular the compound of the formula (IC) (see WO00 / 68225):
• 1,2,4-triazines with activity against parasitic protozoa are known.
• Preferred 1,2,4-triazines are represented by formula (IT):
• R 1 and R 2 independently of one another represent hydrogen or Cl
• R 3 is fluorine or chlorine.
• diclazuril is most preferred.
• the abovementioned active compounds may optionally be present as geometric and / or optical isomers or regioisomers or their isomer mixtures in different compositions. Both the pure isomers and the isomer mixtures can be used according to the invention.
• the active compounds can form salts
• the use in the form of pharmaceutically acceptable salts is also suitable.
• the active ingredients are suitable for favorable toxicity to warm-blooded animals for the control of parasitic protozoa, which occur in livestock and livestock in livestock, breeding, zoo, laboratory, experimental and hobby animals. They are active against all or individual stages of development of the pests and against resistant and normally sensitive strains. By controlling the parasitic protozoa disease, deaths and reductions in performance (eg in the Pro ⁇ production of meat, milk, wool, hides, eggs, honey, etc.) are to be reduced, so that through the use of active ingredients a more economical and easier animal husbandry possible is.
• the parasitic protozoa include:
• Mastigophora such as Trypanosomatidae eg Trypanosoma b. brucei, Tb gambiense, Tb rhodesiense, T. congolense, T. cruzi, T. evansi, T. equinum, T. lewisi, T. percae, T. simiae, T. vivax, Leishmania brasiliensis, L. donovani, L tropica, such as Trichomonadidae eg Giardia lamblia, G. canis.
• Trypanosomatidae eg Trypanosoma b. brucei, Tb gambiense, Tb rhodesiense, T. congolense, T. cruzi, T. evansi, T. equinum, T. lewisi, T. percae, T. simiae, T. vivax, Leishmania brasiliens
• Sarcomastigophora such as Entamoebidae eg Entamoeba histolytica, Hartmanellidae eg Acanthamoeba sp., Hartmanella sp.
• Apicomplexa such as Eimeridae e.g. Eimeria acervulina, E. adenoides, E. alabahmensis, E. anatis, E. anseris, E. arloingi, E. ashata, E. auburnensis, E. bovis, E. brunetti, E. canis, E. chinchilla- e, E clupeamm, E. columbae, E. contorta, E. crandalis, E. debliecki, E. dispersa, E. ellipsoidales, E. falciformis, E. faurei, E. flavescens, E.
• Eimeridae e.g. Eimeria acervulina, E. adenoides, E. alabahmensis, E. anatis, E. anseris, E. arloingi, E. ashata, E. auburnens
• Pneumocystis carinii as well as Ciliophora (Ciliata), e.g. Balantidium coli, Ichthiophthirius spec, Trichodina spp., Epistylis spec
• the active compounds or active compound combinations according to the invention are also active against proteases which occur as parasites in insects.
• parasites of the strain Microsporida in particular of the genus Nosema, may be mentioned.
• the livestock and breeding animals include mammals such as e.g. Cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, fur animals such as e.g. Mink, chinchilla, raccoon, birds such as e.g. Chickens, geese, turkeys, ducks, pigeons, bird species for home and zoo keeping. It also includes farmed and ornamental fish.
• mammals such as e.g. Cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, fur animals such as e.g. Mink, chinchilla, raccoon, birds such as e.g. Chickens, geese, turkeys, ducks, pigeons, bird species for home and zoo keeping. It also includes farmed and ornamental fish.
• Laboratory and experimental animals include mice, rats, guinea pigs, golden hamsters, dogs and cats.
• the fish include farmed, farmed, aquarium and ornamental fish of all ages, living in fresh and salt water.
• the farmed and farmed fish include, for example, carp, eel, trout, whitefish, salmon, bream, roach, rudd, chub, sole, plaice, halibut, Japanese yellowtaü (Seriola quinqueradiata), Japanaal (Anguilla japonica), Red seabream ( Pagurus major), Seabass (Dicentrarchus labrax), Gray mullet (Mugilus cephalus), Pompano, Gilthread seabream (Sparus auratus), Tilapia spp., Chichlid species such as Plagioscion, Channel catfish.
• Particularly suitable are the inventive means for the treatment of fish fry, for example carp of 2 to 4 cm compassion ⁇ length.
• the remedies are also very suitable in the eel mast.
• the application can be both prophylactic and therapeutic.
• Enteral administration of the drugs is e.g. orally in the form of powders, suppositories, tablets, capsules, pastes, potions, granules, drenches, boiled egg, medicated feed or drinking water.
• the dermal application is e.g. in the form of diving (dipping), spraying, bathing, washing, pour-on and spot-on and powdering.
• the parenteral application is e.g. in the form of injection (intramuscular, subcutaneous, intravenous, intraperitoneal) or by implants.
• Suitable preparations are:
• Solutions such as injectable solutions, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, infusion formulations, gels;
• Emulsions and suspensions for oral or dermal application and for injection Semi-solid preparations
• Solid preparations such as powders, premixes or concentrates, granules, pellets, tablets, tablets, capsules; Aerosols and inhalants, active substance-containing moldings.
• Injection solutions are administered intravenously, intramuscularly and subcutaneously.
• Injection solutions are prepared by dissolving the active ingredient in a suitable solvent and possibly adding additives such as solubilizers, acids, bases, buffer salts, antioxidants, preservatives.
• the solutions are sterile filtered and bottled.
• Suitable solvents include: Physiologically acceptable solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol, hydrocarbons, propylene glycol, polyethylene glycols, N-methylpyrrolidone, and mixtures thereof.
• the active compounds can also be dissolved in physiologically tolerated vegetable or synthetic oils which are suitable for injection.
• Solubilizers which may promote the dissolution of the active ingredient in the main solvent or prevent it from precipitating may be mentioned as solubilizers.
• solubilizers examples are polyvinylpyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.
• Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol.
• Oral solutions are applied directly. Concentrates are administered orally after prior dilution to the concentration of use. Oral solutions and concentrates are prepared as described above for the injection solutions, whereby sterile work can be dispensed with.
• Solutions for use on the skin are dripped, brushed, rubbed, sprayed on, sprinkled on or applied by dipping (dipping), bathing or washing. These solutions are prepared as described above for the injection solutions.
• Thickeners are: inorganic thickeners such as bentonites, colloidal silicic acid, aluminum monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and methacrylates.
• Gels are applied to or painted on or placed in body cavities. Gels were prepared by adding solutions prepared as described for the injection solutions with thickening agent sufficient to give a clear mass of ointment-like consistency.
• the thickeners used are the thickening agents specified above. Pour-on formulations are poured or sprayed onto limited areas of the skin, the active ingredient either penetrating the skin and acting systemically or being distributed on the body surface.
• pour-on formulations are prepared by dissolving, suspending or emulsifying the active ingredient in suitable skin-compatible solvents or solvent mixtures. If appropriate, further auxiliaries such as dyes, absorption-promoting substances, antioxidants, light stabilizers, adhesives are added.
• solvents water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenylethanol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, benzyl benzoate, ethers such as alkylene glycol alkyl ethers such as dipropylene glycol monomethyl ether, diethylene glycol mono-butyl ether, ketones such as Acetone, methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide, N-methylpyrrolidone, 2-dimethyl-4-oxy-methylene-l, 3-dioxolane.
• aromatic alcohols such as benzyl alcohol, phenylethanol, phenoxyethanol
• esters such as ethyl acetate, butyl acetate
• benzyl benzoate
• Dyes are all animal-approved dyes that may be dissolved or suspended.
• Absorption promoting substances are e.g. DMSO, spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.
• spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.
• Antioxidants are sulfites or metabisulfites such as potassium metabisulfite, ascorbic acid, butylhydroxytoluene, butylhydroxyanisole, tocopherol.
• Sunscreen agents are e.g. Substances from the class of benzophenones or novantisolic acid.
• Adhesives are e.g. Cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin.
• Emulsions can be used orally, dermally or as injections.
• Emulsions are either water-in-oil type or oil-in-water type.
• a hydrophobic phase may be mentioned: paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic / capric acid biglyceride, triglyceride mixture with vegetable fatty acids of chain length Cg_i 2 or other specially selected natural fatty acids, partial glyceride mixtures saturated or unsaturated, possibly also hydroxyl-containing fatty acids, mono- and diglycerides of Cg / C ⁇ Q fatty acids.
• Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene glycol pelargonate, esters of a branched fatty acid of medium chain length with saturated fatty alcohols of chain length C j gC j g, isopropyl myristate, isopropyl palmitate, caprylic / capric esters of saturated fatty alcohols of chain length C ⁇ -C j g, isopropyl stearate, oleic acid esters, oleic acid decyl esters, ethyl oleate, ethyl lactate, waxy fatty acid esters such as dibutyl phthalate, diisopropyl adipate, the latter related ester mixtures, inter alia fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol
• Fatty acids e.g. Oleic acid and its mixtures.
• hydrophilic phase may be mentioned:
• Alcohols such as e.g. Propylene glycol, glycerol, sorbitol and their mixtures.
• nonionic surfactants e.g. polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ethers;
• ampholytic surfactants such as di-Na-N-lauryl- ⁇ -iminodipropionate or lecithin;
• anionic surfactants such as Na lauryl sulfate, fatty alcohol ether sulfates, mono / dialkyl polyglycol ether orthophosphoric acid ester monoethanolamine salt;
• cationic surfactants such as cetyltrimethylammonium chloride.
• Viscosity-increasing and emulsion-stabilizing substances such as carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes, colloidal Silica or mixtures of the listed substances.
• Suspensions may be administered orally, dermally or as an injection. They are prepared by suspending the active ingredient in a carrier liquid, optionally with the addition of further excipients, such as wetting agents, dyes, absorption-promoting substances, preservatives, antioxidants, light stabilizers.
• carrier liquids As carrier liquids, all homogeneous solvents and solvent mixtures may be mentioned.
• Suitable wetting agents are the surfactants specified above.
• Semi-solid preparations may be administered orally or dermally. They differ from the suspensions and emulsions described above only by their higher viscosity.
• the active compounds are mixed with suitable excipients, if appropriate with the addition of auxiliaries, and brought into the desired form.
• Suitable carriers are all physiologically compatible solid inert substances. All such den ⁇ nen inorganic and organic substances. Inorganic substances are e.g. Common salt, carbonates such as calcium carbonate, bicarbonates, aluminas, silicas, clays, precipitated or colloidal silica, phosphates.
• Organic substances are e.g. Sugar, cellulose, food and feed such as milk powder, animal meals, cereal flours and meals, starches.
• Adjuvants are preservatives, antioxidants, dyes which have already been mentioned above.
• Suitable excipients are lubricants and lubricants such as e.g. Magnesium stearate, stearic acid, talc, bentonites, disintegrants such as starch or cross-linked polyvinylpyrrolidone, binders such as e.g. Starch, gelatin or linear polyvinylpyrrolidone and dry binders such as microcrystalline cellulose.
• lubricants and lubricants such as e.g. Magnesium stearate, stearic acid, talc, bentonites, disintegrants such as starch or cross-linked polyvinylpyrrolidone, binders such as e.g. Starch, gelatin or linear polyvinylpyrrolidone and dry binders such as microcrystalline cellulose.
• the active ingredients may be present in combination with synergists or with other active ingredients.
• polyether antibiotics As further active ingredients in particular polyether antibiotics come into question, such as:
• Semduramicin and especially maduramicin are especially maduramicin.
• Ready-to-use preparations contain the active compounds in each case in concentrations of 0.005 ppm to 50 ppm, preferably from 0.1 to 10 ppm.
• the active compounds in the ratio 1 to 0.01 - 50 to 1 to 1 - 50 before.
• the ratio is I to 25.
• the active ingredients can also be administered together with the feed or drinking water of the animals.
• Feed and food contain 0.005 to 250 ppm, preferably 0.05 to 100 ppm of the active ingredient in combination with a suitable edible material.
• Such food and food can be used both for curative purposes and for prophylactic purposes.
• the preparation of such a feed or foodstuff takes place by mixing a concentrate or a premix containing 0.5 to 30%, preferably 1 to 20% by weight of an active ingredient in admixture with an edible organic or inorganic carrier with conventional feed ⁇ average.
• Edible carriers are e.g. Corn flour or corn and soybean meal or mineral salts, preferably containing a small amount of an edible dust control oil, e.g. Corn oil or soybean oil.
• the premix obtained in this case can then be added to the complete feed before it is fed to the animals.
• Ducks, geese and turkeys 0.005 to 100 ppm, preferably 0.05 to 100 ppm of an active ingredient are mixed with a suitable edible material, eg a nutritious feed. If desired, these amounts can be increased, especially if the active ingredient is well tolerated by the recipient. Accordingly, the administration can be done via the drinking water.
• a suitable edible material eg a nutritious feed.
• preferably amounts of active ingredient of from 0.05 to 100 mg / kg of body weight are administered daily in order to obtain the desired results.
• administering larger amounts it may be expedient to divide them into several individual administrations during the course of the day.
• the effectiveness of the compounds of the invention can be e.g. in caged experiments with the following test arrangement, in which the animals are treated with the respective individual components and with the mixtures of the individual components.
• a medicated feed is prepared so that the required amount of active ingredient is supplemented with a nutritionally balanced animal feed, e.g. with the chick chow specified under, is thoroughly mixed.
• a concentrate or a premix When a concentrate or a premix is to be prepared, which is to be finally diluted in the feed to the values mentioned in the experiment, generally about 1 to 30%, preferably about 10 to 20 wt .-% active ingredient with an edible organic or anorgani ⁇ carrier, eg Corn and soybean meal or mineral salts containing a small amount of an edible de-oiling oil, e.g. Corn oil or soybean oil, mixed.
• an edible organic or anorgani ⁇ carrier eg Corn and soybean meal or mineral salts containing a small amount of an edible de-oiling oil, e.g. Corn oil or soybean oil, mixed.
• the resulting premix can then be added to the whole poultry feed prior to administration.
• the following composition is suitable.
• Such feed contains 18% crude protein, 5% crude fiber, 1% Ca, 0.7% P and 1 kg 1200 i.E. Vitamin A, 1200 i.E. Vitamin D3, 10 mg Vitamin E, 20 mg Zinc bacitracin.
• the infection is carried out by gavage directly into the crop with about 100 000 sporulated oocysts of Eimeria acervulina and each with about 30 000 sporulated oocysts of E. maxima and 40 000 sporulated oocysts of E. tenella. These are highly virulent strains.
• the exact dose of infection is adjusted so that as many as one of three experimentally infected untreated chicks dies due to infection.
• the following criteria are taken into account for the evaluation of the efficacy: weight increases from the beginning of the test to the end of the experiment, infection-related mortality, macroscopic assessment of the faeces with regard to diarrhea and blood excretion on days 5 and 7 pi (evaluation 0 to 6), macroscopic assessment of the intestinal mucosa , in particular the caeca (rating 0 to 6) and the oocyst excretion as well as the proportion (in%) of the oocysts sporulating within 24 hours.
• the number of oocysts in the faeces was determined with the aid of the McMaster counting chamber (see Engelbrecht and co-workers "Parasitological Work Methods in Medicine and Veterinary Medicine, Akademie- Verlag, Berlin (1965)).
• the individual findings are set in relation to the untreated, uninfected control groups and an overall evaluation is calculated (see A. Haberkorn (1986) pp. 263 to 270 in Research in Avian Coc. cidiosis ed. LR McDougald, LP Joyner, PL Long Proceedings of the Georgia Coccidiosis Conference Nov, 18.-20. 1985 Athens / Georgia USA).
• weight% of not inf. control is the ratio of the weight of the treated animals to the weight of the uninfected control group.

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