CA1294216C - Coccidiocidal agents comprising a polyether antibiotic - Google Patents

Abstract

Abstract of the disclosure Coccidiocidal agents which contain a polyether antibiotic from the group of salinomycin or narasin or their salts or esters in combination with one or more active ingredients from the group of meticlorpindol, methyl benzoquate, nicarbazin, amprolium, beclotiamine or halofuginone or its salt show synergistic efficacies. These are considerably stronger than the activities of the single ingredients suggest.

Description

HECHST AKTIENGESELLSCHAFT HOE 86/F 086 Dr.AU/mU

COCG idiocidal ~gents Sal;nomycin and narasin ~s 4-methyLsalinD~ycin) ~re known ~s ~ polyether ~ntibiotic from German O~fenl~ungsschrift 2,353,998 ~nd ~A Antibiotics 30, pages 53D-532 t1977), see also Merck lndex 10th edition, page 920, 1200 (1983).
Their use as ~nticsccidiosis ~gents is ~lso descr;bed there. These antibiotics ~r~ prepared by fer0entation, see ~ritish Patent 1,37R,413 and German Patene 2,525,095.

lt has now been found that the attion of salinomycin and narasin ~hen combined ~ith other known coccidiocidal active compQunds is increased beyond ~he expected degree.

The invention thus rel~tes to cocr,idiocidal 3gents which contain ~ polyether ~ntibiotic ~elected from the group com-prising salinomycin, nar~sln or their physiologically ac-ceptable salt or ester ln combinatlon with one or more actlve compounds æelected from the group comprising meticlor-pindol, m~thyl benzoquate, nicarbazin, amprolium, beclo-tiamine or halo~uginone or its salt.
T~o-component comb;nations are of particular interest.
Three-component combinations can ~lso be used ~ccording to the invention; of the latter, the combination of salinomycin or narasin with meticlorpindol and methyl benzo~uate is preferred.

Instead of ~ m its muxture with ethopabate can be used in these combinations. The o~ination p~ers ~o be used according to the inv~ntion for salinomycin and nar~sin have ~een kno~n in veterinary ~edicine for ~ relatively long ti~e. They are ~ll described in the Merck Ind~x, 10th editi~n, pubLished by Merck ~ Co., Inc. ~S~ (1983): ~etitlorpindol l3,5-dichloro-2,6-dimethyl-4-pyridinol) ~n pD9~ ~41; ~ethyl benroquate ~nequinate; 3-~ethoxyc~rbonyl-6-n-bu~yl-7-ben~yloxy-4-Z~6 oxoquinoline~ on page 928; nicarbazin (complex of N,N'-bis(4~nitrophenyl)urea with 4,6-dimethyl-2(1H)-pyrimidi-none) on page 931; ethopabate ~methyl-(4-acetamido-2-ethoxy-benzoate~on page 544; amprolium (1-~4-amino-2-propyl-5-pyrimidinyl)methyl~-2-methyl- piperidinium chloride~ on page 613; beclotiamine ~3~(4-amino-2-me~hyl-5-pyri~idinyl)-methyl~-5-(2-chloroethyl)~-4~methyl-thiazolium chloride on page 144; and halofuginone (7-bromo-6-chloro-febrifugine) on page 662. In addition to ~alofuginone, physiologically acceptable salts thereof, such as the hydrohalides, in particular hydrobromide, acetate, lactate, alkali metal or alkaline earth metal salts and salt of aceturic acid, see German Offenlegungsschrift 2,934,069, are also included according to the invention, as well as all the optical iso-mers and mixtures thereof. Amprolium or beclotiamine can also be used as their hydrochloride addition salts. Instead of heclotiamine also its analogous naphthalene-1,5-disul-fonate salt can be used accordin~ to the invention.

'l'he combination of meticlorpindol and methyl benzoquate is known as the commercial product ~R~Lerbek (ICI). The com-bination of amprolium and ethopabate is known as the com-mer c~l product (R)Amprol Mix Super (Merck, Sharp & Dohme AGV~T) The combinations according to the ;nvention exhibit syner-gist;c effects in combating toccidiosis, in particular coccidiosis in poultry.

~hen large numbers ~f poultry ~re kept in a confined space, for ~xa~ple in the f~ttening of poultry or rearing of poultry, there is alw~ys the potential danger of a coccidial inf~ction c~used by Eimeria species, and if not combated the~other2Peutically this l~ds eo serious economic lssses. Coccidi~l infections ~s a rule cause depressed weigh~ Dnd excretion of bloodstained dropPings, ~hich srise ~s ~ cons~quence Dt lesisns in the inteseinal ~29~;21~;

~ucous ~embrane. Severe coccidial in~ections ;n poultry as a rule ~lso le~d to ~ high m~rtality.

~y using the conlbinations ~ccording t~ the invention, considerabl2 ~dvanta~es result in co~p~rison ~;th the corresponding individu~l sctive comp~unds, since smaller amounts of coctidiocidal ~ents tan be e~ployed This resu(ts in ~ reduction in the ~oxic s;de e~fetts of the pr~duct in compar;son ~ith odministration of the individual ~ctive compounds, sn incre~se in profitability and ~ reduc-t;on of the residues in ehe edible tissues fro~ th8 poultry.

~he ~eight rdtios of the 3ctive compounds can v~ry ~ithin wide limits in the ~g~n~s according ~o the inven~ion. In combinations o~ ~alinomycin or nar~in with the other in-gredients, t~ey are a) ~ith meticlorpindol, bet~een 5:1 and 1:25, in particu-lar bet~een 1.5:1 ~nd 1:5, b) ~ith ~ethyl ben~oquate, bet~een 100:1 3nd 1:3, in par-ticular bet~een ~0:1 and 5:1, c) ~ith nicnrb~zin, between 6:1 and 1:15, in particular bet~een 3:1 ~nd 1:4, d) with h~lofuginone, bet~een 160:1 ~nd 3:1, in particular between 100:1 and 8~ nd e) ~ith a mixeure of ~etielorpindol and ~ethyl b~n~oquater bet~een 20:1 and 1:20, in particulsr 10:1 and 1:5 f~ with amprolium, between 1:1 and 1:5 g) with beclotiamine, between 1-1 and 1:5~
h) with a mixture of amprolium and ethopabate, between 1:1 and 1:5.
(in each case the values refer to the ratio of he polyether antibiotic to the combination partner).
The weight ratio of meticlorpindol to methyl benzoquate in case 3~ e) can vary between 20:1 and 7:1 whereas ~he weight ratio of amprolium tO ethopabate in case h) can vary between 30:1 and 10:1.

~4~

The compounds ~cc~rding to the invention are quite gener-ally suitable for the protection of poultry, that is to say for the treatment of ~r;cultural commerci~l poultry, such 3s chic~ens~ turkeys~ ducks or ~eese, ~s ~ell as other birds, such as, for example, phe~sants, quail or guinea-~o~l; the latter species of birds have recently aLso been reared in far~s for economic use and, like chickens, are affected Srequently snd massively by Coccidia.

~or success~ul protetti~n of the poultry fr~ coccidiosis, the sgent~ ~ccording to the invention can be used at any ti~e. In p~rticul~r, they c~n be used in broiler farms or houses for r~ring young hens, since there is ~ high risk of infection for the poultry population there because o~ the per~anent forms of th~ Cocc;dia toocysts) continu-ally excreted in the droppings. Since there is al~ays the risk of an ou~bre~k of toccidiosis under thes~ c~nditi~ns, the coccidiocid~l ~gents according to the invention should be used tontinuously on the poultry and before ~n outbreak of coccidiosis. Mo~ever, the agents according to the ;nvention c~n also be administered over short intervals of time, that is to say over a fe~ d~ys.

The use ot the agents according to the invention and methods for combating coccidiosis are carri~d out in the custom~ry m~nner. Oral administr~tion is pri~rily sui~-~ble, in accordanc~ with the location of ehe Coccidia in the intestinal eract. The ~ctive co~p4und combin~tions according to the invention can thereby be ~ixed ~ith feed-3û stuf~s or ~ith drinking ~ater.

~he active co~pound concentr~tions of ~he co~binations inthe feedstuffs or in the drinking ~ater c~n vary ~ithin cert~;n linits. They ~re in gener3l bet~een S ~nd 300 ppm o~ the active compound ~ombina~ion, bas~d ~n t~e feeds~uf~
or drink~ng wat~r.

~;29~;216 The particularly preferred concentrations tor combating coccidiosis are, in the case of the feedstuffr in each case 15 to 70 ppm, in particular 25 to 45 ppm, of salino-mycin or narasin ~nd a) 15 to 150 ppm, in particul~r 30 to 125 ~pm, of meticlorpindol, b) 1 to 30 ppm, in particular 1.25 to 5 ppm, of ~ethyl benzoquate, c) 15 to 150 ppm, in p~rticular 30 to 100 pp~ ~f nicar-baz ln, d~ 0~5 to 3 ppm, in p~rticuLar 0.75 to 1~5 pp~O of halo-fuginone~
e) 5 to 120 ppm, in particulAr 8 to 30 ppm, ot ~eticlor-pindol/nethyl ben20quate~
f) 100 to 150 ppm of amprolium~
g) 40 to 125 ppm of beclotiamine, h) 30 to 100 ppm of amprolium/ethopabate.

If drinkin~ w~ter 15 used, ln each case abo~t hal~ of the concentratlons stated ls pre~erably used.
All the concentr~tions, ratios, p~rtst a~ounts or percen-tages mentioned ~re based on weight units.

The active compound concentr3tions of the coccidiocidal ~gents are based on feed or drink;ng ~ater ~or~ulations ~d libitum, that is to say for free intake of feed or drinking ~ater over ~ fattening or re~ring period cus-tomary in practice. Ho~ever~ because of particular factors resulting in practice, ;~ ~y be that the poultry expert ~ust ~ake ~n up~ard adjust~ent in these use concentr~tions if the poultry is suPplied ~ieh different stocks of feed or ~ter. ~n that case, ho~ever~ only so~e of ~he feed or ~ater stocks contains ~the ~gents accGrding ~c the inven-tion.

~4;~16 Suitable vehicles for the synergisticalLy active coccidio-eidal agents ~ccording to the invention are all the feed formulations customary in the poultry industry. The for-~ulations for poultry feed described belo~ are e~amples of ~ormulations ~hich and customary in practice, Ho~ever, it is ~oreover ~lso possible to US2 other feedstuffs based on ~ny c@real grains and tontaining vitamin concentrates, ~ineral concentrates or other ~ct;ve tompounds and feed ~dditives in ~ny desired concentration. 80th conventional dry, ~ealy or pelleted ~eedstuffs and liquid suspension feeds, ;ncludin~ f~edstu~s such as distillation pulp and ~;lk by-products, c~n be used with the agents according to the invention.

To prepare the poultry feed according to the invention, A concentrated premix contDining the synergistically active coccidiocidal agents in a high concentrstion, for example from 0~2 to 75Z, is usually f;rst prepared. For this purpose, the coccidiocidal agents and physislog;cally 2~ ~ccept~ble vehicles, such ~s propylene glycols, polyethy-lene glycols, inert oils, such ~s v~getable oils, highly refined ~ineral oils, ethanol, ~ater or ~queous alcohols, either are dispersed or ~re 0ixed into inert ~ehicles, such as vermiculite, diatomaceous earth, attapulgite, c~lcium carbona~e or bolus alba. Organic vehicles, such as ~heatbran, co~rse cornmeal, soybean flour, lucerne flour, rice husks or ground corn cobs, ~nd uny other desired or~anic veh;cles from vegetable prnducts, ~re like~ise suit~ble for this purpose.

~2~Zl~

The synergist;cally ~ctive agents ~ccording to the inven-~ion can furthermore also be administered to poultry together ~ith the drinking ~ter~ They ~re incorporated into the drink;ng ~aeer by ~dd;ng ~ su;table ~mount of a ~ater-soluble or w3ter^suspendable form of the particular agent to the drink;ng ~ater. 5uch ~or~ulat;ons Are in ~ener~l prepared by sel~ctiny a ~a~er-soluble form of the bgents. lf this is undesir~ble or cannot ~e prepared, ~ater-insoluble forms, for example suspens;ons, can also be used.
1~ Physiologit~lly ~ccept3bLe ~uxiliaries~ ~ith which the coccidiocidal a~ent~ according to the invention ~re kept in suspensions in ~ater over ~ prolonged period, are used to pr~p~re the for0ul~tions. ~uxiliaries which ~re suit-able for this ~re s~elling ~3ents, such as ~l~in~tes, gelatin, carboxymethylcellulose or polyvinylpyrrolidone.
Ho~ever, the agents ~ccording to the invention c~n also be suspended ~ith various surface-active compounds, sueh as, for example, ~i~h the aid of Lecithin, naph~halene-sulfonates~ ~lkylben~enesul~onates, alkylphenol-poly-ethylene oxide adducts or polyoxyethylene sorbit~n esters.A concentr~ted suspension or ~ dry formulat;on of the coccidiocid~l 2gen~s accord;ng to the invention ~nd the suspending agonts in cert~in ~ixin~ ratios is usually first prepared, and is then diluted wieh the drinking ~ter to the desired use ccncentration, or the premixes ~re ~ixed in suit~ble concentrations ~ieh the feedstuffs tustomary in practice. The drinking ~ater or feed oædit~ted in this ~ay is then offered to the poultry, either initi~lly ad libitum or ov~r ~ c~rt~in ~r;od~

The tre~t~ent ~ethod according to the invention can also be ex~ended tG other methods for the treatment ond feeding of poultry. If, for examp~e, the compositions according to the invention can be combined with other active com-pounds, such as, for example, ~i~h gro~th-promoting agents or antiparasit;cs, uhich on the one hand are 3ynthet;c agents or on the other hand are fermentation products in the broadest sense.

~lthough the invent;on is particularly directed to~ards ehe protection of pouLtry from coccidial infections, it can also accordingl~ be used on other domest;c Dnd commer-eial ~nimals~ such ~s, for example~ o~her birds, rabbits, hogs and rumin~nts.

The inveneion thus ~lso relaees to a ~ethod for ehe treat-~ent of poultry coccid;osisO ~hich comprises administering the abovementioned ~ctive ~gents orally ad libitum to poultry, and in particular either as a feedstuff or by ~eans of the drinking ~ater.

The inventicn is illustrated by the follo~ing examples.

A. Examples of animal feed compositions , ~ . _ ~he follouing e~amples relate ~o ~nimal feed compositions ~hich can be used for administration of the active compound combination according eO the invention.

I ~
.

Fishmeal ~60-65X) ~.0 Feeding yeast 2.0 Beef tallo~ 4.7 Soybean ~eal (44~) 2400 Luc~rne ~eal 1.0 C~rn 44.89 Wheat 6.35 ~2~ 16 g ~heat ~hite shorts 8.5 Calcium phosphate 1.4 Calcium carbonate 0.96 Trace elsment premix 0.04 S Cattle salt 0-09 DL-methionine 07 100.0 a) ~ :
V;tamin A I.U. 12,DD0 93 I.U. 1,500 E ~9 18 ~1 ~9 1.5 ~2 ~9 6 P~ntothenic ~cid ~9 9 Nicotinic acid ~g 24 Vitamin B6 ~9 4.5 e~2 ~cg 24 K3 mg 3 Choline chloride m9 10300 b) 1.0 kg of_feed contains .

Mn ~g 106 Zn mg 71 Fe mg 44 Cu mg 3.56 I mg 0.4 Co mg 0.16 lI. ~ (0-8th ~eek) ~Fishme~l (60-~S~) : 5,0 Lucerne ~eal ~.o Soybean meal ~4bX~ 13.0 feedin~ ye3st 2.8 ~eet tallo~ 2~0 Barley 6.0 Oats 6.0 Sorn 37.0 ~heat 13.0 Whea~bran 703 Calcium carbonate feed talc 1.29 tR)Nostaphos Trace element premix* 0 04 10D.O

See Example Ib); Yit~mins as described in Example la) are furthermore added.

III. ~ ~9th-20th ~eek) Lucerne ~eal 6.0 Soybe~n meal (44X) 10.24 Feeding yeast 1~8 Beef tallo~ 2.0 8arley 8.0 Oats 6.0 Corn 40.0 ~heat 15.0 ~he3tbr~n 8.3 Calcium carbonate 1.53 ~R)Host~phos 1.02 Trace element prem;x 0.04 DL-methionine 0 07 100 . O

: : See Example Ib); vitamins are furthermore added, see Example Ia) :
IV. ~ (from the 21st ~eek) tomposit_on in X by wei~ht Fishme~l ~60-65X) 1.5 Soybean ~eal S4bX) lQ.31 ~eef tallo~ 1.0 Oats 6.7 Corn 40.0 Wheae lB.O
S ~heat ~hite shorts 3~
DL-methionine 0007 Feed paprika 0,3 Salcium carbonate 8.16 ~R)Hostaphos 1.91 Trace element premix 0.05 100.0 Vitamins as described in Ex3mple Ia3 are furthermore ~dded~

V. Feed for_turkeys ~composition in ~ by weight3 Turkey Turkey ~urkey starter fatten;ng fattening feed feed I feed II
0-8th ~eek 9th-12th 13th-16th ~ eek _ week Fishmeal 9.0 5.0 2.0 Feeding yeast 4.5 2~ .0 Fflt 3.1 g.7 Soybean ~eal 26.0 23.9 23~87 Lucerne ~eal 4.~ 2.0 0.95 ~arley 5.3 4.5 5.0 : Oats 1.0 ~.45 Corn 3S.04 40.02 39.9D
~he3t 5.3 S.O 5.0 Wheat ~hite shcrts 5~95 470 3.8 ~heatbran 4.0 Calcium phosph3te 1.58 1~30 2.71 Calcium c~rbon~te 1.35 1.~ D.9$
Trace ele~ent pre-~ix~ 0.04 n.o4 \ 0.04 C~ttle s~lt 0.24 0.84 O.b4 Uethionine 0.1 0.1 0 18 100,0 100.D 100.0 Vitamin mixture per kg of feed _ . . . _ Vitamin A ~.U. 12,0D0 8,0D0 8,000 D3 I.U~ 1,500 1,DOD 100~0 E mg 1~ 12 12 B1 ~9 1.5 ~2 ~9 b.O 4 4 Pantothenic acid mg 9.0 6 6 Nicotinic acid ~9 24.0 16 16 Vitamin ~ ~9 4.5 3 3 B12 mcg 24.0 16 16 K3 ~9 3~0 2 2 Choline ehloride mg ~,3D0 1,300 1,300 1 kg of feed contains: 106 ~g of Mn; 71 ~g of Zn;
44 mg of Fe; 3.56 ~9 of Cu; 0.4 mg of I3 D.16 mg of Co.

. Biological ex3mples The coccidiostatic effect of the present agents has been investigated on chickens infected ~ith Coccidia, The experimental investig~tions described below demsnstrate the efficacy of the v~rious combinations according to the invention with the aid of a few examples. The salinomycin is used here in the form of ~ sodium salt of the mycelium ~hich has been prepared by fermentation and has not been separ~ted.

To deeer~ine and evaluate the coccidiostatic effect of the agents according to the invention, so-called in~ection controls (untreated~ ;n~ected birds) 3nd ~ero controls tuntre3ted, non-intected birds) ~re used in ~ll the gxperimental investig~tions descr;bed belo~. The birds of both sexes used for ~hese (LSL chickensO Loh~nn, ~allau, FRG) ~ere randomi~ed and groups of 16 Dnimals each ~ere ~ade up~ The infected groups treated ~ith the agents : ~ccording to th~ inv~ntion ~ere ~de uP by the s~me ~ethod. The bir~s, ~xcluding those of the ~ero control, ~ere infected with a viru~ene Eimeria tenella strain, which leads to severe (reProducible) lesions in the ceca in S-days old chickens. The coccidiocidal 3gents ~ere mi~ed ~ith the feed for pou~ry in ppm amounts; the particular concentrations can be seen from the follo~ing Tables la to 1e.

The degree of ~everity of the pathological-~natomical changes in the ~ucous ~embrane in the ceca caused by the infection is usually (ExperimentaL Pardsi~ology VoLume 28, ~5 1970; or Lon~, P.L.: ~he ~iology of ehe CGCC idia, 19R2, Univ. Park Press) expressed in the form of damage values (= lesion vaLues)~ called " ~ " belo~ ~scaLe from 0 to 4~. At the end o~ the investigations, the animals ~ere s~crificed 5 ~ays ~fter infection and ~ere : 15 investigated for all the typical pathologic~l ~natomical changes caused by cocc;diosis.

Description and evaluation of ~he damage tlesion scores):
0 to 4 . _ 0 - birds in ~hich no lesions are detectable in the intestinal tract 1 - birds ~ith ~ few circu~scribed sm~ll lesions (pet-echiae) in the eeca 2 - birds ~ith several, circ~mseribed lesions tpet-echiae) some~hat larger tban described under 1 3 = birds ~i~h numerDus hemorrhagic lesions of a relatively large area and partly tontluent.

4 = bords ~ith large ~re3 he~orrha~ic lesions, ~hith af~ert the entire intestinal ~ucous ~embran~ of the c~ca ~nd 2lso adj~cent sections of the intestine ; 30 tileu~ and rectu~)~ The pict~re of extremely severe hemorrhogic ~nteritis over ~ l~r~e ~re~, ~hich 3S a rule leads to the death of the bird, is prevented.

~z~

Liquid and bloodsta;ned dropping are ;ncreasing~Y de-posited ~ith the damage described under 1 to 4. The depressed ~eight as a result of refusal of food likewise torrelates ~ith the intrease in "Lesion scores"~

The relevance of the lesion scores for evalu3ting the coccidioc;dal actic~n of the agents accordin~ to the invention bec~mes clear from the observations mentioned.

~he lesion scores are l;sted in Tables 1a-le, on the one hand as individual values per snimal w;thin a group, and on the other hand as mean values of the corresPonding yroup o~ birds.

ln all the experi~ents, groups of 16 LSL chickens one week old ~ere kept under constant housing cond;tions in ~;re cages containing 4 birds each per ~ire cage. The feed medicated ~ith the agents ~ccording to the invention uas offered ad libitum from day D-1 (one day before infection) untiL day D+S t5 days ~fter infection). The control groups tzero group and infection control) received non~edicated ~eed. The particular ~roups of birds ~ere thus fed with the same feed for 7 days. On the day of infection ~= DO), 200,000 sporulated oocysts of the abovementioned E.
tenella strain ~ere ~dministered to each bird by a stomach eube.

~tter parti3l digestion of the oocysts in the s~all intes-tine, the infectious sporo~oites ~ere rele~sed from these permanent forms and then attacked the epitheli3l cells of ehe intestinal ~ucous membr~ne and multiplied there ~assively by changing ~or~. ~he numerous schiz~nts ~hich develop from the sporo~oites destroy ~he intestin3l epi-~heliu~ by repe3ted division processes. ~ pe~k of the destructive ef~ect of the schizonts on the intes~inal epiehelium is reached 5 days ~fter infectionO ~he "lesion scores" ~ere therefore determined at this point in time _ ~5 -;n the manner described above.

The synergist;c effect of the agents according to the invention tcombinations~ is sho~n below in ~Dbles la-1e, and in part;cular, on the one hand the effect of the indi-vidual acti~e compounds in the use concentration rustomaryin practice, and on the other h~nd the super~dditive or synergistic effect resulting ~rom various co~binations of the individual active compound. The 'lles;on scores" of ~he infec~;on controls ~nd ehe zero controLs ~non-infected animals) ære used for balancing with the particular medi-cated and infected groups of ~nimals.

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Claims (16)

1. A coccidiocidal agent which contains a polyether antibiotic selected from the group comprising salinomycin, narasin or their physiologically acceptable salt and ester in combination with one or more active compounds selected from the group comprising meticlorpindol, methyl benzoquate, amprolium, beclotiamine or halofuginone or its salt.

2. An agent as claimed in claim 1, which contains salinomycin or narasin in the form of its physiologically acceptable salts or esters.

3. An agent as claimed in claim 2, which contains salinomycin or narasin in the form of its alkali metal or alkaline earth metal salts.

4. An agent as claimed in claim 2, which contains salinomycin or narasin as the sodium, potassium, ammonium, magnesium or calcium salt.

5. An agent as claimed in claim 3, which contains salinomycin or narasin as the sodium, potassium, ammonium, magnesium or calcium salt.

6. An agent as claimed in claim 1, 2 or 3, which contains salinomycin or narasin as the Na salt.

7. An agent as claimed in claim 4 or 5, which contains salinomycin or narasin as the Na salt.

8. An agent as claimed in claim 1, which contains salinomycin or narasin as the mycelium or crude product.

9. An agent as claimed in claim 1, 2 or 3, which contains salinomycin or narasin in combination with meticlorpindol and methyl benzoquate.

10. An agent as claimed in claim 4, 5 or 8, which contains salinomycin or narasin in combination with meticlorpindol and methyl benzoquate.

11. An agent as claimed in claim 1, 2 or 3, which contains salinomycin or narasin in combination with amprolium and ethopabate.

12. An agent as claimed in claim 4, 5 or 8, which contains salinomycin or narasin in combination with amprolium and ethopabate.

13. An agent as claimed in claim 1, 2 or 3, which additionally contains poultry feed or drinking water.

14. An agent as claimed in claim 4, 5 or 8, which additionally contains poultry feed or drinking water.

15. The use of an agent as claimed in claim 1, 2 or 3, for combating poultry coccidiosis.

16. The use of an agent as claimed in claim 4, 5 or 8, for combating poultry coccidiosis.