MXPA96004044A - Anticoccidiales de carbanil - Google Patents
Anticoccidiales de carbanilInfo
- Publication number
- MXPA96004044A MXPA96004044A MXPA/A/1996/004044A MX9604044A MXPA96004044A MX PA96004044 A MXPA96004044 A MX PA96004044A MX 9604044 A MX9604044 A MX 9604044A MX PA96004044 A MXPA96004044 A MX PA96004044A
- Authority
- MX
- Mexico
- Prior art keywords
- average
- carbanilide
- media
- square
- trifluoromethylsulfonyloxy
- Prior art date
Links
- 230000001165 anti-coccidial Effects 0.000 title description 10
- DGTNSSLYPYDJGL-UHFFFAOYSA-N Phenylisocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 title description 2
- -1 1,1,2,2-tetrafluoroethylsulfonyloxy Chemical group 0.000 claims abstract description 116
- 150000001875 compounds Chemical class 0.000 claims abstract description 51
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims abstract description 5
- 229920001774 Perfluoroether Polymers 0.000 claims abstract description 4
- 125000001475 halogen functional group Chemical group 0.000 claims abstract description 4
- RFMQOHXWHFHOJF-UHFFFAOYSA-N cyano thiocyanate Chemical compound N#CSC#N RFMQOHXWHFHOJF-UHFFFAOYSA-N 0.000 claims abstract description 3
- GWEHVDNNLFDJLR-UHFFFAOYSA-N 1,3-diphenylurea Chemical compound C=1C=CC=CC=1NC(=O)NC1=CC=CC=C1 GWEHVDNNLFDJLR-UHFFFAOYSA-N 0.000 claims description 84
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 28
- 208000003495 Coccidiosis Diseases 0.000 claims description 22
- 206010023076 Isosporiasis Diseases 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 239000002460 polyether antibiotic agent Substances 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
- 235000013305 food Nutrition 0.000 description 29
- 230000000968 intestinal Effects 0.000 description 24
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 24
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- 241000223932 Eimeria tenella Species 0.000 description 20
- 238000000034 method Methods 0.000 description 20
- 229920000570 polyether Polymers 0.000 description 20
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 18
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- 229910052799 carbon Inorganic materials 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- 241000223931 Eimeria acervulina Species 0.000 description 15
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
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- AYYDIRTZCUFMDY-UHFFFAOYSA-N (4-aminophenyl) trifluoromethanesulfonate Chemical compound NC1=CC=C(OS(=O)(=O)C(F)(F)F)C=C1 AYYDIRTZCUFMDY-UHFFFAOYSA-N 0.000 description 9
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- NDTIXHNCNLKURN-UHFFFAOYSA-N (4-nitrophenyl) trifluoromethanesulfonate Chemical compound [O-][N+](=O)C1=CC=C(OS(=O)(=O)C(F)(F)F)C=C1 NDTIXHNCNLKURN-UHFFFAOYSA-N 0.000 description 2
- QZTWVDCKDWZCLV-UHFFFAOYSA-N 1-isocyanato-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(N=C=O)C=C1 QZTWVDCKDWZCLV-UHFFFAOYSA-N 0.000 description 2
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Abstract
The present invention relates to a compound of the formula: characterized in that: R1 represents perfluoroalkylsulfonyloxy of C1-C8 or 1,1,2,2-tetrafluoroethylsulfonyloxy, with the limitation that if R2 is not present, R1 is located in the 4-position. R3 represents C1-C8 perfluoroalkylsulfonylox or 1,1,2,2-tetrafluoroethylsulfonylox, with the limitation that if R4 is not present, R3 is located at the 4 'position, each of R2 and R4 independently represents nitro, halo, cyano, thiocyanate, trifluoroacetylthio, perfluoroalkyl of C 1 -C 2, 1,1,2,2-tetrafluoroethyl, perfluoroalkoxy of C 1 -C 2, 1,1,2,2-tetrafluoroethoxy, perfluoroalkylthio of C 1 -C 2, 1,1,2, 2-tetrafluoroethylthio, C1-C2 perfluoroalkylsulfinyl, 1,1,2,2-tetrafluoroethylsulfinyl, C1-C2 perfluoroalkylsulfonyl or 1,1,2,2-tetrafluoroethylsulfonyl; m represents 0; 1 represents 0, 1 and 2; myn is 1, 2
Description
A TICOCCIDIALES DE CARBANILIDA
Coccidiosis is a disease that animals suffer. This is caused by protozoan organisms, typically the Eimeria. This is particularly devastating among poultry kept in captivity. Many chemotherapeutic agents are used to control the disease. However, there is a risk that the causative organisms will develop resistance after constant or repeated exposures to any particular chemotherapeutic agent. There is also a desire to employ chemotherapeutic agents that are active at low percentages, to minimize the risk of residues, or to reduce the period of time during which the poultry are untreated before being slaughtered to eliminate waste. The search for improved chemotherapeutic agents for the control of coccidiosis therefore continues. The present invention provides a novel and improved chemotherapeutic agent for the control of coccidiosis. The invention provides novel carbanilide compounds, the methods of using the compounds for the control of coccidiosis, and premixes of animal feed and animal feeds which REF: 23053 contain the compounds. The invention also includes the use of the subject compounds in combination with polyether antibiotics. The novel carbanilide compounds of the present invention are defined by the following formula:
wherein R1 represents perfluoroalkylsulfonyloxy of Ci-Cβ or 1,1,2,2-tetrafluoroethylsulfonyloxy, with the limitation that if R2 is not present, R1 is located at the 4 'position; R3 represents perfluoroalkylsulfonyloxy of C? -Cβ or 1,1,2,2-tetrafluoroethylsulfonyloxy, with the limitation that if R4 is not present, R3 is located at the 4 'position; each R 2 and R 4 independently represent nitro, halo, cyano, thiocyanate, trifluoroacetylthio, C 1 -C 2 perfluoroalkyl, 1,1,2,2-tetrafluoroethyl, C 1 -C 2 perfluoroalkoxy, 1,1,2,2-tetrafluoroethoxy, C 1 -C 2 perfluoroalkylthio, 1,1,2,2-tetrafluoroethylthio, C 1 -C 2 perfluoroalkylsulfinyl, 1,1,2,2-tetrafluoroethylsulfinyl, C 1 -C 2 perfluoroalkylsulfonyl, or 1,1,2,2- tetrafluoroethylsulfonyl; m represents 0 or 1; n represents 0, 1, or 2; and the sum of yn is 1, 2, or 3. An important element of those compounds is the group "R1" (and the group "R3" when additionally present.) The compounds of the present invention, wherein both R1 and R3 = perfluoroalkylsulfonyloxy are a preferred embodiment of the present invention, symmetrical compounds are often preferred:
Among perfluoroalkylsulfonyloxy groups, those of C 1 -C 5 are preferred, and those of C 4 -C 4 are often more preferred. The trifluoromethylsulfonyloxy compounds are especially preferred. The substituents R2, if present, are preferably located ortho or ortho and for substituent R1. Preferences similar to the other rings are related when they contain a substituent R3. The present carbanilide compounds are prepared by the known synthesis techniques for the carbanilide compounds. In general, there are two preferred synthetic routes. The first synthetic route is the reaction of an appropriately substituted aniline with an appropriately substituted isocyanate, to produce the desired compound of the present invention.
This reaction is conducted according to the conditions known for this reaction. Typically, the reactants are mixed in a reaction medium, which may be a chlorinated hydrocarbon, DMF, THF, ether, or aromatic hydrocarbon. The reaction proceeds under a wide variety of temperatures, such as from 0 ° C to 100 ° C. However, no advantages have been observed in using low or high temperatures, and more conveniently the reaction is conducted simply at room temperature. The reaction consumes the reagents in equimolar amounts, and as such are used in a desirable manner. The reaction is preferably conducted under nitrogen, to avoid oxidation of the aniline. In addition to that a small amount of a tertiary amine is catalytic. The product is isolated and purified if desired with standard techniques. This synthetic route is illustrated by Examples 1-10, below. A variation of this synthetic route is particularly suitable for the preparation of the symmetrical compounds of the present invention - that is, the compounds wherein m = 1, R = R3, and any further substitution (R2, R4) is identical. These compounds are conveniently prepared by reacting the aniline defined above with phosgene, triphosgene or another reagent which converts the NH2 to an isocyanate. The resulting isocyanate compound reacts directly with the remaining aniline to produce the desired symmetrical compound. This variation is illustrated in Examples 11-13 below. The substituted anilines employed in this synthetic route are prepared themselves from nitrophenols, by reducing the nitro and esterifying the hydroxy group. The sequence of these two reactions is not critical, except that in the group R1 it is somewhat unstable under high temperatures. It is therefore preferred, either, to first reduce and subsequently esterify, or first to esterify and subsequently reduce the nitro group by dissolving a reducing metal, for example, Zn / Cu / HCl in aqueous methanol at ~60 ° or stannous chloride / HCl / Water. H2 / Pd reduction is successful only if the temperature can be maintained below about 25 ° C. A second preferred synthetic route for the present carbanilide compounds is the esterification of a hydroxycarbanilide by means of an appropriate reagent, to obtain the desired compound of the present invention:
The esterifying agent can be a fluorinated alkylsulfonic acid anhydride of the formula (R5S02) wherein R5 represents C? -C8 perfluoroalkyl or 1,1,2,2-tetrafluoroethyl; the corresponding fluoride (R5S02F), or an imide of the formula (R5S02) 2NAr wherein xxAr "is an aryl moiety such as phenyl or pyridyl The anhydride of perlfuoroalkylsulfonic acid in. wherein R5 = trifluoromethyl known as triflic anhydride, is a preferred reagent for the synthesis of the compounds wherein R1 (and R3 if present) = CF3S020- When the alkyl chain in R1 exceeds two carbons, the trifluorides are the preferred reactants.The reaction consumes equimolar amounts of the hydrocarbanilide and the esterifying agent, but a slight excess of esterifying agent is preferred.The reaction generates the corresponding sulfuric acid, and triethylamine or another acid receptor is typically provided to the reaction mixture.The reaction proceeds at temperatures over a range, such as from -70 ° C to 25 ° C. The work and purification are carried out within the standard procedures.This synthetic route is illustrated by l Examples 17 and 19. In addition to the above synthetic methods, certain carbanilides can be prepared from other carbanilides, by techniques well known to those skilled in the art. The oxidation of an unclean substituent is an example of this technique, this is illustrated in Example 18. A review of the article on "Uses of the Trifilo Group in Organic Synthesis", Organic Preparation & Procedures International 9, 175-207 (1977), is incorporated herein by reference. The synthesis of the present carbanilide compounds is illustrated by the following examples. P-Nitrophenol (14.00 grams, 0.1 mole) and triethylamine (10.17 grams, 0.1 mole) were mixed in 500 ml of methylene chloride. Triflic anhydride (28.42 grams, 0.1 mol) was added. The reaction mixture was stirred for one hour, checked by TLC (Thin Layer Chromatography), and an additional 2 grams of triflic anhydride was added. The reaction mixture was stirred another half hour, then worked up, yielding 4- (trifluoromethylsulfonyloxy) -1-nitrobenzene. 4- (Trifluoromethylsulfonyloxy) -1-nitrobenzene (27.1 grams, 0.10 mole) in 300 ml of ethanol was added dropwise to 94.8 grams of stannous chloride (0.5 mole, 5 equivalents) in 525 ml of concentrated HCl, at room temperature. Addition rate was controlled to prevent the temperature of the reaction mixture from rising. The reaction mixture was stirred for 3 hours, 10 N NaOH was added until the pH was ~ 12, and it was extracted into ether. The ether extract was washed with water, dried over magnesium sulfate, and the ether was evaporated to yield 4- (trifluoromethylsulfonyloxy) aniline as a yellowish brown oil. His identity was confined by NMR, EM, and elemental analysis, the last of which showed:
Theorist Found Carbon 34.85 35.10 Hydrogen 2.51 2.57 Nitrogen 5.81 5.89 Example 1 4 '- (Trifluoromethylthio) -4- (Trifluoromethyl-sulfonyloxy) carbanilide
4- (Trifluoromethylsulfonyloxy) aniline (1.00 grams, 0.0041 mol) was mixed with 15 ml of methylene chloride at room temperature under nitrogen. A few drops of triethylamine were added. The 4-trifluoromethylthio) phenyl isocyanate (0.90 grams, 0.0041 mol) in 15 ml of methylene chloride was added dropwise, and the resulting reaction mixture was stirred for two hours. An equal volume of cyclohexane was added and the methylene chloride was evaporated, yielding a white solid, which was separated and recrystallized from isopropanol, m.p. 230-232 ° C. The elemental analysis showed Carbon Theoretical Found 39.13 39.39 Hydrogen 2.19 2.26 Nitrogen 6.09 6.19
Example 2 '-Nitro-4- (Trifluoromethylsulfonyloxy) carbanilide
The title compound was prepared by reacting the 4-nitrophenyl isocyanate with 4- (trifluoromethylsulfonyloxy) aniline with the same general procedures described in Example 1. The compound melted at 243-245 ° C and had the following elemental analysis:
Theorist Found Carbon 41 .48 41.74 Hydrogen 2. 49 2.49 Nitrogen 10 .37 - 10.58
Example 3 4 / - (Trifluoromethyl) -4- (Trifluoromethylsulfonyloxy) carbanilide
The title compound was prepared by reacting 4- (Trifluoromethyl) phenyl isocyanate with 4-trifluoromethylsulfonyloxy) aniline with the same general procedures described in Example 1. The compound melted at 212-214 ° C and had the following elemental analysis:
Theorist Found Carbon 42 .06 41.94 Hydrogen 2. 35 2.38 Nitrogen 6. 54 6.31 Examples 4 and 5 4'-Chloro-3 '- (Tri luoromethyl) -4- (Trifluoromethylsulfonyloxy) carbanilide and 2'-Chloro-3'- ( Trifluoromethyl) -4- (Trifluoromethylsulfonyloxy) carbanilide
The title compound was prepared by reacting the 4-chloro-3- (trifluoromethyl) -phenyl isocyanate with 4- (trifluoromethylsulfonyloxy) aniline with the same general procedures described in Example 1. The 4'-chloro-3'- ( trifluomethyl) isomer melted at 192-194 ° C and had the following elemental analysis:
Theorist Found Carbon 38 .93 39 .67 Hydrogen 1. 96 2. 05 Nitrogen 6. 05 6. 01
The 2'-chloro-3 '- (trifluoromethyl) isomer melted at 167-170 ° C and had the following elemental analysis:
Theorist Found Carbon 38.93 40.12 Hydrogen 1.96 2.21 Nitrogen 6.05 5.89 This had a small amount of starting material.
Example 6 4'-Bromo-4- (Trifluoromethylsulfonyloxy) carbanilide
The title compound was prepared by reacting the 4-bromophenyl isocyanate with 4- (trifluoromethylsulfonyloxy) aniline with the same general procedures described in Example 1. The compound melted at 207-208 ° C and had the following elemental analysis:
Theorist Found Carbon 38. 28 38. 15 Hydrogen 2. 29 2. 39 Nitrogen 6. 38 6.42
Example 7 4'-Chloro-2 '- (Trifluoromethyl) -4- (Trifluoromethylsulfonyloxy) carbanilide
The title compound was prepared by reacting the 4-chloro-2- (trifluoromethyl) phenyl isocyanate with 4- (trifluoromethylsulfonyloxy) aniline with the same general procedures described in Example 1. The compound melted at 160-161 ° C and had the following elementary analysis:
Theorist Found Carbon 38.92 38.95 Hydrogen 1.96 2.14 Nitrogen 6.05 6.29
Example 8 2'-Chloro-5 '- (Trifluoromethyl) -4- (Trifluoromethylsulfonyloxy) carbanilide
The title compound was prepared by reacting the 2-chloro-5- (trifluoromethyl) phenyl isocyanate with 4- (trifluoromethylsulfonyloxy) aniline with the same general procedures described in Example 1. The compound melted at 184-187 ° C and had the following elementary analysis:
Theorist Found Carbon 38.92 39.21 Hydrogen 1.96 2.03 Nitrogen 6.05 6.11 Example 9 4 '- (Trifluoromethylthio) -3-Chloro-4- (Trifluoromethylsulfonyloxy) carbanilide
The title compound was prepared by reacting 4- (trifluoromethyl) phenyl isocyanate with 3-chloro-4- (trifluoromethylsulfonyloxy) aniline with the same general procedures described in Example 1. The compound melted at 207-209 ° C and had the following elementary analysis:
Theorist Found Carbon 36.41 36.70 Hydrogen 1.83 2.10 Nitrogen 5.66 5.43
Example 10 4 '- (1, 1, 1, 2-Tetrafluoro tiltio) -4- (Trifluoromethylsulfonyloxy) carbanilide
The title compound was prepared by reacting the isocyanate of 4- (1,1,1,2,2-tetrafluoroethylthio) phenyl with
4- (trifluoromethylsulfonyloxy) aniline with the same general procedures described in Example 1. The compound melted at 213-215 ° C. The compound can be oxidized by Example 18, to obtain the corresponding compound 4 '- (1,1,2,2-tetrafluoroethylsulfonyl).
Example 11 4.4 '-Bis (Trifluoromethylsulfonyloxy) carbanilide
4- (Trifluoromethylsulfonyloxy) aniline (2.1 grams, 0.001 mole) and triphosgene (0.6 grams, 0.003 mole) were mixed in 60 ml. of 1.2 dichloroethane. The reaction mixture was stirred at reflux while triethylamine (3 mL) was added dropwise. After refluxing for one hour, the reaction mixture was a clear solution. This was balanced with 10 mi. of ether and with 50 ml. of 2N HCl. The solution was then dried over magnesium sulfate and evaporated to dryness. The residue was suspended with 10 ml. of 1,2-dichloroethane and 50 ml of cyclohexane, and filtered to isolate the product as a white solid. This melted at 238-240 ° C and had the following elemental analysis:
Theorist Found Carbon 35.44 35.21 Hydrogen 1.98 2.18 Nitrogen 5.51 5.27 Example 12 3.3 -Dichloro-4,4-BIS (Trifluoromethylsulfonyloxy) carbanilide
The title compound was prepared by reacting the 3-chloro-4- (trifluoromethylsulfonyloxy) aniline with triphosgene the same general procedures of Example 11. The product melted at 252-253 ° C.
Example 13 3,3 '-Bis (Trifluoromethyl) -4,4' -Bis (Tri- Fluoromethylsulfonyloxy) carbanilide
The title compound was prepared by reacting the 3-. { trifluoromethyl) -4- (trifluoromethylsulfonyloxy) aniline with triphosgene with the same general procedures of Example 11. The product melted at 218-220 ° C.
Example 14 A '-Cloro-3,3' -Bis (Trifluoromethyl) -4- (Trifluoromethylsulfonyloxy) carbanilide
4'-Chloro-3, 3'-bis (trifluoromethyl) -4-hydroxycarbanilide (1.00 grams, 2.51 mmol) was added at 10 ml. of methylene chloride. Triflic anhydride (9.78 grams, 2.76 mmol) was added dropwise, followed by triethylamine (0.56 grams, 5.52 mmol), also added by dripping. The reaction mixture turned dark purple. After three hours, the reaction mixture was evaporated to a dark purple gum. NMR showed the desired product as well as triethylamine. The gum was chromatographed on a two-inch silica pad in ethylene chloride, taking 50 ml cuts. The 1-6 cuts contained the product and cuts 3-5 were combined and evaporated to a light brown foam. Ether was added to the foam and evaporated to a white matt foam. The identity of the product was confirmed by NMR.
Example 15 3 'A' -Dichloro-3- (Trifluoromethyl) -4- (Trifluoromethylsulfonyloxy) carbanilide
The 3 ', 4' -Dichloro-3- (trifluoromethyl) -4-hydroxycarbanilide and the triflic anhydride were reacted, with essentially the same procedures as in Example 14, to yield the title compound, m.p. 170-172 ° C.
Example 16 A '-Nitro-3- (Trifluoromethyl) -4- (Trifluoromethylsulfonyloxy) carbanilide
The 4'-Nitro-3- (trifluoromethyl) -4-hydroxycarbanilide and the triflic anhydride were reacted, with essentially the same procedures as Example 14, to produce the title compound. This melted at 226-227 ° C and had the following elemental analysis;
Theorist Found Carbon 38.07 38.49 Hydrogen 1.92 2.13 Nitrogen 8.88 9.04
Example 17 3,4 '-Bis (Trifluoromethyl) -4- (Trifluoromethylsulfonyloxy) carbanilide
3, 4 '-Bis (trifluoromethyl) -4-hydroxycarbanilide and triflic anhydride were reacted with essentially the same procedures as Example 14, to produce the title compound. This melted at 141-143 ° C with decomposition and had the following elemental analysis:
Theorist Found Carbon 38.72 38.98 Hydrogen 1.83 2.01 Nitrogen 5.64 5.83
Example 18 A '- (Trifluoromethylsulfinyl) -4- (Trifluoromethylsulfonyloxy) carbanilide and A' - (Trifluoromethylsulfonyl) -4- (Trifluoromethylsulfonyloxy) -carbanilide
4 '- (Trifluoromethylthio) -4- (trifluoromethyl-sulfonyloxy) carbanilide (6 grams, 0.012 mol) and 33 percent hydrogen peroxide (9 ml) were mixed and stirred at 25 ° C in 40 ml of trifluoroacetic acid. A precipitate formed after about 10 minutes; the CCF suggested the sulfinyl compound (S = 0). The reaction mixture was stirred at 25 ° C for 16 hours, then the TLC showed both sulfinyl and sulfonyl groups. The reaction mixture was heated at 60 ° C for one hour, and subsequently cooled and stirred at 25 ° C for 24 hours. Water (60 ml) was added and the reaction mixture was filtered, the isolated sulfonyl product was dried with air and recrystallized from 1,2-dichloroethane, m.p. 256-257 ° C (centigrade). The product had the following elementary analysis:
Theorist Found Carbon 36. 59 36. 64 Hydrogen 2. 05 2. 00 Nitrogen 5. 69 5. 67
Example 19 A '- (Trifluoromethylthio) -4- (Trifluoromethylsulfonyloxy) carbanilide
This compound, illustrated in Example 1, was also prepared by an alternative method. In this alternative preparation, the 4 '- (trifluoromethylthio) -4-hydroxycarbanilide (2.60 grams; 0.008 mmol) was mixed with 20 ml. of methylene chloride at 0 ° C. Triethylamine (0.88 grams, 0.0088 mmol) was added dropwise, followed by triflic anhydride (2.46 grams, 0.0088 mmol) in a small amount of methylene chloride. The reaction mixture was stirred at 0 ° C for four hours, during which time samples were taken at various times and verified by thin layer chromatography to detect the presence of starting material. After the first two samples, additional triflic anhydride and triethylamine were added. The third sample indicated virtually the absence of starting material and the reaction mixture was worked. The methylene chloride was evaporated, approximately 75 ml were added. of ether, and the resulting mixture was washed three times with IN HCl, dried over magnesium sulfate, and evaporated to remove the ether. The residue was suspended in methylene chloride, filtered, washed with 2N NaOH, and filtered. The product had the following elementary analysis:
Theorist Found Carbon 39.13 39.39 Hydrogen 2.19 2.26 Nitrogen 6.09 6.13
Example 20 A '- (Trifluoromethylsulfonyl) -3-nitro-4- (trifluoromethylsulfonyloxy) carbanilide
The 4"- (Trifluoromethylsulfonyl) -3-nitro-4-hydroxycarbanilide and the triflic anhydride were reacted with essentially the same procedures of Example 14 to produce the title compound, which melted at 175-176 ° C and had the following elemental analysis:
Theorist Found Carbon 33.52 33.82 Hydrogen 1.69 1.81 Nitrogen 7.82 7.56
Other representative compounds of the present invention include the following: 4 '- (trifluoromethylthio) -4- (1, 1,2,2-tetra-fluoroethylsulfonyloxy) carbanilide 4' - (trifluoroethylsulfonyl) -4- (1, 1, 2 , 2-tetra-fluoroethylsulfonyloxy) carbanilide 4 '- (1,1,1,2,2-tetrafluoroethylthio) -4- (1,1,2,2-tetra-fluoroethylsulfonyloxy) carbanilide 4' - (trifluoromethylthio) -4- (perfluoro -n-butylsulphonyloxy) carbanilide 4 '(1,1,2,2-tetrafluoroethylthio) -4- (perfluoro-n-butylsulfonyloxy) carbanilide 4' - (1, 1,2, 2-tetrafluoroethylsulfonyl) -4- ( perfluoro-n-butylsulfonyloxy) carbanilide 4 '- (trifluoromethylthio) -4- (perfluoro-n-octylsulfonyloxy) carbanilide 4' - (trifluoromethylsulfonyl) -4- (perfluoro-n-octylsulfonyloxy) carbanilide 4 '- (1 , 1,2,2-tetrafluoroethylthio) -4- (perfluoro-n-octylsulfonyloxy) carbanilide 4 '- (1,2,2-tetrafluoroethylsulfonyl) -4- (perfluoro-n-octylsulfonyloxy) carbanilide 4' - (trifluoromethylsulfonyl) ) -3-nitro-5- (trifluoromethyl) -2- (trifluoromethyl sulphide) nyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3-nitro-5- (trifluoromethyl) -2- (perfluoro-n-butylsulfonyloxy) carbanilide 4' - (trifluoromethylsulfonyl) -3- (trifluoromethyl) -4- (trifluoromethylsulfonyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3-chloro-5- (trifluoromethyl) -4- (trifluoromethylsulfonyloxy) carbanilide 4' - (trifluoromethylsulfonyl) -3-nitro-5- (trifluoromethyl). 4- (trifluoromethylsulfonyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3- (trifluoromethyl) -4- (perfluoro-n-butylsulfonyloxy) carbanilide 4' - (trifluoromethylsulfonyl) -3-chloro-5- (trifluoromethyl) -4 - (perfluoro-n-butylsulfonyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3-nitro-5- (trifluoromethyl) -4- (perfluoro-n-butylsulfonyloxy) carbanilide 4'-thiocyanato-3-chloro-5- (trifluoromethyl) -4- (trifluoromethylsulfonyloxy) carbanilide 4'-thiocyanato-3- (trifluoromethyl) -4- (trifluoromethylsulfonyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3-chloro-4- (trifluoromethylsulfonyloxy) carbanilide 4' - (trifluoromethylsulfonyl) -3,5-dichloro-4- (trifluoromethylsulfonyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3-fluoro-4- (trifluoromethylsulfonyloxy) carbanilide 4'- (trifluoromethylsulfonyl) -3,5-difluoro-4- (trifluoromethylsulfonyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3-chloro-4- (perfluoro-n-butylsulfonyloxy) carbanilide 4' - (trifluoromethylsulfonyl) -3,5-dichloride o-4- (perfluoro-n-butylsulfonyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3-fluoro-4- (perfluoro-n-butylsulfonyloxy) carbanilide 4' - (trifluoromethylsulfonyl) -3,5-difluoro-4- (perfluoro) -n-butylsulfonyloxy) carbanilide 3, 3'-bis (trifluoromethyl) -4,4'-bis (trifluoromethylsulfonyloxy) carbanilide 3, 3'-bis (trifluoromethyl) -4,4'-bis (perfluoro-n-butylsulfonyloxy) ) carbanilide 3, 3 '-difluoro-4,4'-bis (trifluoroethyl-sulphoryloxy) carbanilide 3, 3'-difluoro-4,4'-bis (perfluoro-n-butylsulphonyloxy) carbanilide 3, 3' - dichloro-4,4'-bis (trifluoromethylsulphonyloxy) carbanilide 3, 3'-dichloro-4,4 '-bis (perfluoro-n-butylsulphonyloxy) carbanilide 3, 3', 5, 5'-tetrachloro-4 4 '' -bis (trifluoromethyl-sulfonyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3-cyano-4- (trifluoromethylsulfonyloxy) carbanilide 4' - (trifluoromethylsulfonyl) -3-cyano-4- (perfluoro-n) -butylsulfonyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3-chloro-5-cyano-4- (trifluoromethylsulfonyloxy) carbanilide 4 '- (trifluoromethylsulfonyl) -3-chloro-5-cyano-4- (perfluoro-n-butylsulfonyloxy) carbanilide 4'-thiocyanato-3-cyano-4- (perfluoro-n-butylsulphonyloxy) carbanilide A '-thiocyanato-3-chloro-5-cyano-4- (perfluoro-n-butylsulfonyloxy) carbanilide 4' - (trifluoroacetylthio) -4- (trifluoromethyl-sulfonyloxy) carbanilide 4 '- (trifluoroacetylthio) -3-chloro-4- (trifluoro-methylsulfonyloxy) carbanilide 4 '- (trifluoroacetylthio) -3, 5-dichloro-4- (trifluoroethylsulfonyloxy) carbanilide 4 '- (trifluoroacetylthio) -3-fluoro-4- (trifluoromethylsulfonyloxy) carbanilide 4'-nitro-4- (perfluoro-n-pentylsulfonyloxy) -carbanilide
The present invention can be used for the control of coccidiosis in any species. Chickens and turkeys are the species most commonly treated for coccidiosis, but the present invention can also be used with other species of poultry, such as ducks, geese, quails, pheasants and ostriches. The invention can also be practiced with species other than poultry, such as cattle, sheep, pigs and the like. The present invention can be used to prevent or treat coccidiosis attributable to any species. The species that commonly cause coccidiosis in chickens are Eimeria acerv? Lina Eimeria brunetti Eimeria maximus Eimeria necatrix Eimeria tenella The species that commonly cause coccidiosis in turkeys are Eimeria meleagrimitis Eimeria gallopavonis Eimeria adenoeides Eimeria dispersed Coccidiosis in other species is attributable to other species of protozoa better known to those skilled in the art. The present invention is practiced in the usual form of anticoccidials, that is, since coccidiosis is a disease of the intestinal tract, an anticoccidial must be administered in such a manner as to reach the intestinal tract. This is typically achieved by incorporating the present agents into the forage. Anticoccidials are sometimes administered via drinking water, and this route is also possible for the present carbanilide compounds. In the most commonly preferred practice, however, the present compounds are administered in the food or feed. The present invention contemplates using a carbanilide compound as an anticoccidial agent; also contemplates using carbanilide in combination with a polyether antibiotic.
Polyethers are a known class of antibiotics that share common structural characteristics. A review article is found in the Kir -Other Encyclopedia of Chemical Technology 4th Ed. Volume # 3, pages 306-322, this article is incorporated herein by reference. Polyethers exhibit anticoccidial activity, and are currently the main chemotherapeutic agents, worldwide, for the control of coccidiosis. The use in the field of many other anticoccidials other than polyethers led to the rapid development or selection of resistant strains. This means that such anticoccidials were of very little value subsequently. The polyethers are unique with respect to the matter of resistance. Some resistance has been confirmed. Its occurrence has not been disseminated, and when it occurs, it generally does not lead to a complete loss of effectiveness. Because of these and their other advantages, polyether antibiotics remain an effective tool for the control of coccidiosis. The present carbanimides are capable of controlling the coccidiosis attributable to the polyether-resistant strains. The combinations of the present carbanilides and the polyethers similarly control the coccidiosis attributable to the polyether resistant strains.
In addition, the use of such combinations is expected to prevent or delay the development of polyether resistance, and thus provide a new tool in the prevention and treatment of coccidiosis. Therefore, in one embodiment of the present invention, a carbanilide was used as the sole anticoccidial, or in combination with a poieter, to prevent or treat coccidiosis due to a polyether-resistant protozoan. Representative polyethers that can be used in the present invention include the following; the annotated reference patents are incorporated herein by reference.
monensin 3,501,568, laidlomycin grisorixina nigericin dianemycin lenoremicina salinomycin 3,857,948 narasin 4,038,384 antibiotic Ionomycin X206 septamicina allorixina antibiotic A204 3705238 lasalocid eteromicina 3,719,753 lisocellina isolasalocida antibiotic A23187 4,582,822 portmicin (antibiotic A80190) 4,683,204 antibiotic kijimicina A82810 5,098,834 maduramicin factor A (X-4868A) 4407946 maduramicin factor C (LLC-23024B) semduramicin
The present active agents are incorporated into an animal feed in the usual form of anticoccidials. Typically, a carbanilide compound, as well as a polyether, are incorporated into a "premix". The premix contains the active agent or agents as well as physiologically acceptable carriers and food products. The premix is relatively concentrated and is adapted to be diluted with other carriers, vitamin and mineral supplements, and food products to form the final animal feed. Premixes of intermediate concentration of active agent between a first premix and the final animal feed are sometimes used in industry and can be used in the implementation of the present invention. When a carbanilide compound is employed as the sole active agent, a desirable premix contains the agent at a concentration of 0.1 to 50.0% by weight. Preferred premixes will generally contain a carbanilide compound at a concentration of 0.5 to 25.0% by weight. When both a carbanilide compound as well as a polyether are employed, the desirable premix contains concentrations of 0.2 to 25.0% by weight of each active agent. The combination therapy can also be obtained by using a premix containing the carbanilide compound and a second premix containing the polyether. Both mixtures are added to carriers, vitamin and mineral supplements, and food products to produce a single animal forage that contains both active agents. The identity of the other components of the premix and the final animal feed is not critical; Exemplary formulations are listed below. In forages or end foods, the concentration of carbanilide, and polyether, if employed is not critical will depend on several factors known to those skilled in the art. Such factors include the relative potency of the particular carbanilide and polyether; and the severity of the coccidial challenge. In general, a forage or final feed using a carbanilide as the sole active agent will contain the carbanilide in a concentration of 0.001 to 0.02% by weight. In the case of combination therapy, a final forage will typically contain the carbanilide at a concentration of 0.0001% to 0.01% by weight, and the polyether at a concentration of 0.0001% to 0.01% by weight. The advantages of combination therapy are maximized if each of the two active agents makes a significant contribution to the total anticoccidial action. In general, carbanilide and polyester are employed in a ratio of 1: 5 to 5: 1. Those skilled in the art will be able to readily determine the appropriate concentrations of carbanilide and polyether antibiotic. Various compounds to be employed according to the present invention were evaluated in a standardized battery test. In this test, the respective compound was well mixed with a small portion of the basic diet, to constitute a premix, and the resulting premix was added to a large amount of the same basic diet. This resulted in the final diet to feed the birds, which contained the respective compound. This diet was in the form of a dough.
The battery test was conducted with Peterson and Hubbar male chickens or Nicholas female turkeys, beginning when the birds were approximately nine days old. There were usually four birds per cage and one to four cages per treatment. All birds were housed in steel cages, 13"x 21" x 9. "The respective diet and water were provided ad libitum beginning around day 9. All birds except those from the uninfected control group were infected with two or three. Eimeria species Some of the strains exhibited resistance to polyethers The infection was by culture incubation of sporulated oocysts, usually two days after the start of the test (in some tests, one day after the start of the test). maintained during the trial for approximately 9 days, at which time they were sacrificed and the intestinal tracts were evaluated to determine the extent of the lesions attributable to coccidiosis.Other parameters evaluated during the trial were mortality, weight gain, and food / The composition of forage or staple food for chickens was as follows:
Ingredients% Yellow corn 51., 796 Soy flour (48.5%) 34. 626 Animal tallow 6., 970 Meat and bone meal 4. .000 Salt (NaCl) 0.355 Dicalcium phosphate 0., 601 D, L -methionine 0,, 276 Natural calcium carbonate 0,, 926 Mineral premix traces, CK-01 (1.00) l 0, .100 Vitamin premix, CK-02 (1.03) 2 0, .250 Selenium premix,. 02% J 0 .100 Total 100.00
1 Traces of mineral premixes provide 80 mg of Mn, 75 mg of Zn, 60 mg of Fe, 8 mg of Cu, and 1 mg of I per kg of forage or whole food. 2 The vitamin premix provides 8000 IU of vitamin A, 2700 IU of vitamin D3, 20 mg of vitamin. E, 1.5 mg of vitamin K, 45 mg of niacin, 12 mg of pantothenic acid, 8 mg of riboflavin, 3 mg of pyridoxine, 2 mg of thiamine, 800 μg of folic acid, 80 μg of biotin, 15 μg of vitamin Bi2 , 500 mg of choline and 125 mg of ethoxyquin per kg of food or complete fodder.
3 The selenium premix provides 200 μg of Se per kg of feed or whole forage. The composition of the food or forage for turkeys was as follows:
Ingredients% Yellow Corn 31.9 Soybean Oil Flour, Peeled Extracted with Solvents (49%) 46.0 Animal Fat (Beef Seed) 5.0 Fish Meal with Soluble Substances 5.0 Alfalfa Meal, Dehydrated (17%) 2.5 Soluble Solids Dried Distilled of Corn 5.0 Diccalcic Phosphate (Food Grade) 2.2 Calcium Parbonate (Natural Calcium Carbonate) 1.4 Vitamin Premix, TK-01 (1.03) 0.5 Salt (NaCl) 0.3 Trace of Mineral Premix TK-01 (1.02) 2 0.1 Hydroxy-analogs of Methionine 0.1 Total 100.0
1 The vitamin premix provides 3000 ui of vitamin A, 900 uci of vitamin D, 40 mg of vitamin E, 0.7 mg of vitamin K, 1000 mg of choline, 0.10 mg of vitamin B12, 0.10 mg of biotin and 125 mg of ethoxyquin per kg of food or complete fodder. 2 The mineral premix traces provide 75 mg of β1, 50 mg of Zn, 25 mg of Fe and 1 mg of I per kg of whole forage feed. The final feed or feed had the respective carbanilide compound of concentrations of 10 to 100 ppm, which equals 0.001 to 0.01% by weight. In those combination therapy trials, the carbanilide compound was present at concentrations of 10 to 60 ppm, equivalent to 0.001 to 0.006% by weight, and the polyether was present in concentrations of 10 to 60 ppm equivalent to 0.001 to 0.006% by weight . The results of the conducted trials as described above are reported in the following tables. The "#" of columns refer to the number of cages. Orality was reported using both (1) due to all causes ("Total"), and (2) due to coccidiosis ("DTC"), only. The weight gain was calculated only for the surviving chickens. The calculations of the food: gain ratio include the mortality weights. Lesions were scored on a scale of 0-12 (intestinal) and 0-4 (cecal), with 0 indicating no lesions and 12 or 4 indicating maximum lesions. Statistical analyzes were carried out by means of the Multiple Student-Ne Man-Keul Intervals Test, using the Gerbhardt Algorithm for samples of unequal size. The means within a column without common alphabetical superscript differ (P <.05).
lab i Inoculated with E. acervulina and E. tenía Score of the lesions Treatment Average Mortality Weight Gain Food / gain Cecal PPM # Total% U DTC% U Mean # Mean »Mean tt Average NC 0 0.0 to: oo 255.4? 2 1,343 a *) 0.00 c 0.00 b
0 -. 0 -) 0.0 to 2: .o a - '. D z 1 o57 a 2 6.00 a 2 3.63 'a Example 1 20 12.5 i 2 o. or a 192.4 a-b 2 1.981 a b. o3 a 2 3.o7 a
40 0.0 to 2: or 196. ^ a-b 2 1.692 a 2 2.75 b 2 1.13 -b * 0 2 12.5 a 2 o. or a 238.9 a-D 2 1,482 a 2 0.67 0.46 b 90 2 0.0. a 2 0.0 a 225.0 a-b 2 1.440 a 0.00 2 3.38 13
Square Fountain Square Square Square Square Square Variety df Half df Half df Half df Half df Half df Medium "
Error of 93.3 5 3.0 1S20. "5 ..105 5 .8.30 5.53 Treatment t> 104.2 or 0.0 332.5 6 0.061 -J 0.33 3.15 Table 2 Inoculated with E. tenella and E. acervulina Score of the injuries Treatment Mortality Average Gain of Weight Food / Earnings Cecal PPM # Total% # DTC% U Average # Average # Average # Medi-i 0.0 to 4 to 4 1. 35.: 4 0. 5 4"> 13 c. ic o o.3 to 4 216.0 - 4 1.853 a 4 8.75 4 3 33 a
Example 1 40 0.0 to 3.0 343.6 to 4 1.36b. "9 4 C. 1 c 50 0.0 to 3.0 330.2 aD 4 1,360 3.26 4 0.39 or ßO 0.0 A 3.0 aD 4 1.331 4 0.00 4 3.06 b 7 0.0 a 3.0 394.5 1.478 - c 4 0.00 4 3.00 b 80 0.0 a 3.0 -.722 • b 4 3.00 4 0.06 D
Square Fountain Square Square Square Square Square Variation df Half df Half df Half df Half df Half df Medium
Error of 7 174.1 7 55.1 ^ 11623.4 3.21-1 '39.52 9.77
Treatment -2 ^ 3.1 22 35.5 22 534.1 22 22 0.29 22 3.04 Table 3 Inoculated with E. Tenella, laboratory strain and maximum E r Score of Injuries
Treatment Average Mortality Weight Gain Alimento Intestinal Ear Gain
PPM # Total% DTC% # Media # Media # Media # Media
NC 0 4 0.0 b 4 0.0 b 4 368.3 a 4 1.325 c 4 0.19 c 4 0.00 c
0 4 25.0 ab 1 25.0 a 4 147.9 d 4 2.490 a 4 3.06 a 4 3.94 a Example 1 40 4 6.3 b 4 0.0 b 4 303.6 4 1542 r 4 4.08 b 4 1.06 b 50 4 0.0 b 4 0.0 b 4 322.0 b 4 1.410 c 4 1.00 4 0.56 ti-c bO 4 6.3 b 4 0.0 b 4 327.1 b 4 1.438 4 0.31 c 4 0.15: 70 4 0.0 b 4 0.0 b 4 317.1 b 4 1.395 c 4 0.13 c 4 0.00 30 4 6.3 b 4 0.0 b 4 225.0 4 1.826 b 4 0.25 c 4 0.00
Square Fountain Square Square Square Square Square Vari ounce df Media df Media df Media df Media di 'Media df Media
Error of 7 528.3 7 428.6"20411.8 0.632 7 35.58 7 9.96 Treatment 22 134.9 22 5o.3 22 639.9 22 0.026 22 1.33 ¡2 0.12 Table 4 Inoculated with E. eleagrimitis, E. gallopavirus and E. adenoeides Score of Injuries
Treatment Average Mortality Weight Gain Food / gain Cecal Intestinal
PPM # Total% # DTC% # Media # Media # Media »Average-NC 0 2 0.0 to 2 0.0 to 177.9 to 2 1,240 b 2 0.00 0-00 b
3 2 0.0 to 2 .0 to 97.3 b 2 1,766 to 2 7.75 a - > 2.63 • a
Example 1 20 3.0 a 2 \ 0 a 112.2 b 1.628 3 2 6.63 ab 2 0.33 b 40 2 0.0 a 3 0 a 149.1 a 1.374 D 2 o.63 ab 0.00 b 60 2 0.0 a 0.0 d 2 i'4.6 a 2 1.283 b 2 6.38 ab 0.00 b 80 0.0 a 2 0.0 a 2 164.6 a 2 1.214 b 2 4.25 ac "> 0.00 b 20 CO a? 1" .4 a 1.277 b 2 0.63 cd 0.00 D 40 2 0.0 a 2 a 130.5 1,300 D 1.25 cd 2 0.00 b 60 2 0.0 a - > 3 '.0 a 195.6 a 2 1.218 b 2 3.63 b-d 0.00 b 30 0.0 a 3.0 a 1".6 a 2 1.197 b 2 0.63 c-d 2 3.00 b
Square Fountain Square 1 Square Square Square Square Vari atiza df Media df Medium df Half df Half df Half df .Media
Error of a 0.0 9 3.0 9 1847.3 1 5 0.074 9 17.67 a 1.36 Treat icntc 0.0 10 3.0 157.4 10 3.005 10 1.23 10 0.03
Table 5 Inoculated with E i. acervulina. E. maximum and E ',. tenella Score of Injuries
Treatment Average Mortality Weight Gain Alimento Intestinal Ear Gain
PPM * Total% n DTC% # Media U Media tt Media U Media
NC 3 2 0.0 a 2 0.0 a 2 336.6 a-b 2 1.323 c 2 0.00! f 2 0.00 b 2 0.0 a 1 3.0 a 2 286.2 b-c 2 1.552 'a 2 6.88 a -b 2 3.75 a
Example 1 10 2 3.0 a 2 3.0 a 2 293.9 a-c 2 1,560 a 2 6.00 a -c 2 3.00 a
40 2 0.0 a 2 3.0 a 2 334.3 a-b 2 1.321 - 2 4.00 b 2 3.25 t
Portmiciiia 10 2 0.0 to 2 0.0 to 261.0: 2 1,544 to 2 3.00. 3 2 3.38 a
40 2 0.0 to 0.0 to 2 324.1 a-b 2 1.368 b-c 2 4.25 b 3.13 a
Portmicin and Example 1 10.10 2 12.5 a 2 12.5 a 2 313.0 a-b 2 1.517 a-b 2 6.25 a -b 2 2.63 a
. 20 2 0.0 to 2 0.0 to 2 330.8 a-b 1.371 b-c 3.13 - «2 0.50 b
40. 40 2 0.0 to 0.0 to 2 321.9 a-b 2 1.327 c 2 1.38 e -e 2 3.00 b
Sal.nomycin 66 2 0.0 a 2 3.0 a - 295.0 a-c 2 1,449 a-c 2 5.25 a -d 2 3.25 a
MaxibanF 100 2 0.0 a - 0.0 a 2 350.0 a - > 1.309 c - 2.33 d - 0.63 b
Square square font (square square square)
It varies »df Average df Average df Average df Average df Average df Average.
Error of 10 23.4 10 23.4 10 1397.3 10 0.022 10 12.03 10 4.83
Treatment - * • 28.4 28.4 11 237.9 11 0.003 11 0.81 11 0.23.
Table 6 Inoculated with I E. adenoeides,, E. mcleagrimitis Score of Injuries
Treatment Average Mortality Weight Gain Food / gain Cecal Intestinal
PPM * Total% # DTC% n Media »Media H Media # Media
NC 3 2 0.0 a 2 3.0 a .39.0 i 2 1.-80 b 2 0.25 b - o.oo 2 0.0 a 2 0.0 a 34.6 b 2 2.215 b 2 9.25 a; 2.25 a-b
Portmicin 13 2 0.0 a 2 3.0 a "9.1 0 2.142 b eco b ~ • 3.00 .- 40 2 3.0 a 2 3.0 a 2 44.6 2 3.067 a 2 0. ^ o" .30 - Example 1 30 2 0.0 a - > 3.0 a ~ > 37.J or 2 2.264 D 0.53 to 3.50 B-c
40 2 3.0 a - > 0.0 to 100.8 c 2 1.341 2 2 - .33 a 2 3.25 a
Portmicin and Example 1 20 * 20 2 0.0 to 2 0.0 to 2 94.8 b 2 1,838 b 2 0.75 b 3.00:
40 * 40 2 0.0 a 2 0.0 a •) 105.1 b 2 1.-05 b - > 1.50 b 3.00 - Square Fountain Square Square Magnet Square
Variety df Media f Media df Media df Media df Media df Media
Error of "" 0.0 3.0 1441.1 3.392 24.1S 3.36
Treatment '0.0 9 C.O 9 165.3 9 3.050 9 1.31 8 3.22
Table? Inoculated with E. tenella and E. acervulina Score of Injuries Treatment Mortality Average Weight Gain Alimentaganancia Intestinal Cecal
PPM U Total% n DTC% # Media # Media # Media it Media
NC 0 2 0.0 to 2 3.0 to 2 246.0 to 2 1.362 to 2 0.00 - 2 0.00;
3 2 3.0 a 2 '0.0 a 2 158.8 a 2 1,766 a 2 9.17 a 2 3.33 a
Example 11 25 2 0.0 a 2 0.0 a 2 196.0 a 2 1,595 a • '.33 a-b 3.00 a
50 2 16.7 a 2 16.7 a 2 139.1 a 2 1.562 a 2 7.17 a -b 2 4.00 a
100 2 0.0 to 2 0.0 to 2 230.3 to 2 1,400 to 2 4.00 b -c • 1.83 b
Example 13 25 2 .3.0 a 2 3.0 a 2 138.5 a 2 1.627 a 2 7.83 a -b 2 3.67 a
50 2 lo. a 2 0.0 a 2 1".3 a 2 2.050 a 2 8.75 a -b 2 3.75 a
100 2 0.0 to 2 3.0 to 2 1-7.6 to 2 1639 to 2 7.50 to -b 2 3.33 a
Example 1 25 2 16.7 a 2 16.7 a 2 228.4 a 2 1,541 a 2 7.17 a -b 2 3.67 a
50 2 3.0 a 2 0.0 a -) 235.7 a 2 1.349 a 2 1.83 - 2 1.33 o
100 2 0.0 to 2 3.0 to 2 229.4 to 2 1.375 to 2 0.00 c 2 0.00 C
Square Fountain Square Square Square
Variety < if Media df Media df Media df Media df Media df Media
Error of 121.2 10 90.9 .3 3 ^ 24.5 30 0.087 13 23.71 .0 4.49 - Treatment 11 151.5 11 101.0. 517.4 11 0.042 1 1.96 il 0.24
Table 8 Inoculated with E. maxim and E. tenella Injury Score
Treatment Average Mortality Weight Gain Alimento Intestinal Ear Gain
PPM # Total% n DTC% # Media # Media # Average H Average
NC 3 4 0.0 d 4 3.0 to 4 353.7 to 4 1,346? 4 3, 30 3. 0 i j 4 25.0 a-c 4 25.0 a 4 186.6. »- f 4 2.187 a 4 3.63 a 3.13 a
Portmicin 15 4 31.3 a 4 31.3 a 4 1S .1 í 4 2.241 a 4 3.33 3.75 a
33 4 0.0 to 4 3.0 d 4 2: 5.6 b-d 4 1,681 fc-c 4 - 69 to 2.94 a
45 4 3.0 d 4 3.0 d 4 298.0 a-z 4 1,561 b-c 4 5.50 0 3.13 a
-0 4 C.O d 4 0.0 a 4 0 .5 a- 4 1.474 D-C 4 1.33 1 1.44 b
Example 1 ^ c 4 31.3 a 4 12.5 b 4 219.9 a 4 2.115 a 4} .00 to 3. 1 a
3 * Ó 4 12.5 a-d 4 0 0 d 4 235.1 a-c 4 1,632 b-c 4 3.44 a 1.42 b
45 4 0.0 d 4 0.0 d 4 322.7 a-c 4 1.376 b-c 4 3.13 c 3.06 J bO 4 12.5 a-d 4 3.0 d 4 314.2 a-c 4 1.479 D-C 4 3.90 d 3.00 i
Portmicin and Example 1 15 * 15 4 0.0 d 4 0.0 d 4 317.8 a-c 4 1.411 b-c 4 3.13 i.19 b-c
* 30 4 6.3 a-d 4 3.0 d 4 322.8 a-c 4 1.425 b-c 4 3.23 i 3.21 i
* 45 4 0.0 d 4 0.0 d 4 330.5 a-c 4 1419 b-c 4 i - 3.30 1
* 60 4 6.3 a-d 4 0.0 d 4 321.9 i-C 4 1,451 b-c 4 Ó!? 6 i 3.13 d
* 15 4 0.0 d 4 0.0 d 4 329.0 a-c 4 1.438 b-c 4 0.75 d 3.63 c-d
* 30 4 0.0 d 4 0.0 d 4 326.1 i-c 4 1. 1 '' b-c 4 0.00 1 3.30 d
* 45 4 0.0 d 4 0.0 d 4 323.4 a-c 4 1.455 b-c 4 0.06 i C 30 d
* 60 4 0.0 d 4 0.0 d 4 338.1 a-c 4 1.432 b-c 4 3.13 d 3.30 d
45 * 15 4 3.0 d 4 3.0 d 4 341.5 to 4 1.357; 4 0.19 i 3.30 d
45 * 30 4 0.3 a-d 4 3.0 d 4 32"'.5 a-c i 1.417 D-C 4 0.30 d 0.30 d
4S * 45 4 12.5 a-d 4 0.0 d 4 233.3 a-b 4 1.432 b-c 4 0.00 i 3.33 d
45 * 60 4 o.3 a-d 4 3.0 d 4 294.8 a-c 4 1499 b-c 4 3.00 d 3 30 d oO-lS 4 6.3 a-d 4 0.0 d 4 327.1 a-c 4 1.395 b-c 4 0.17 i 3.00 i
= 0 * 30 4 6.3 a-d 4 0.0. 4 31 ^ .3 a-c 4 1.441 b-c 4 0.30 i C .30 i
60-45 4 3.0 d 4 0.0 d 290.3 a-c 4 1.506 b-c 4 0.06 -i 3.30 d o 3 * o0 4 25.0 a-c 4 0.0 2 4 251.4 c-a 4 1.705 0 4 3.30 d 3 33 i
Square Fountain Square Square Square
Variable chalk df Media df Average df Average df Average df Average dt Media
Error of 25 408. - 25 252.2 25 «140.4 25 0.249 25 45.91 25 6.58
Treatment 8 120 .: "" 8 30.0"8 -40.3" 9 0.016"9 3.73 -9 3.19 Table 9 Inoculated with E. tenella and E. acervulina Score of the injuries
Treatment Average Mortality Gain of P? so Cecal Food / Gain
PPM u Total% DTC il Media ti Media tt Average # Media
NC 3 0.0 e 0.0 ß 4 336.7 a-c 4 1,382 d-e 4 0.00 e 0.00 .- CI 3 0.0 0.0 e 4 275.5 ß-í 4 1,623 a-b 4 5.63 a 3.13 a
Portmicin 15 6.3 a-ß 0.0? 4 317.5 a-e 4 1.518 a-ß 4 3.31 c 3.69 a
6.3 a-e 6.3 a-0 4 304.5 a-e 4 1,525 a-e 4 1.69 d 3. "" I a
45 3.0 e 0.0 e 4 339.0 a-c 4 1.447 c-e 4 0.44 e 2.38 b
60 12.5 to 0.0 * 4 306.2 a-a 4 1,521 a-e 4 0.00 e 1.96 b
Example 1: c 6.3 a-ß 6.3 1-D 4 289.2 d-í 4 1,631 a 4 4.56 b 3.50 a
33 6.3 a-a 0.0 e 4 315.6 a-e 4 1.479 a-e 4 1.13 d-e 0.23:
45 0.0 e 0.0 < s 4 318.4 a-e 4 1,458 b-e 4 0.00 e 0.00 c
60 6.3 a-ß 0.0 e 4 321.8 a-d 4 1,417 c-e 4 0.00 e 0.00 c
Portmicin and Example 1 15 * 15 0.0 e Q.O • > 4 331.9 a-d 4 1,400 d-e 4 0.69 2.13 b
* 30 0.0 to 3.0 3 4 349.1 to 4 1,388 d-e 4 0.06 9 0.06 c
* 45 0.0 3.0% 4 341.0 a-b 4 1,390 d-e 4 0.00 «? 0.00"- 15 * 60 0.0 e 3.0 • 5 4 329.9 a-d 4 1,459 b-e 4 0.00 0.13 c
* 15 0.0 0.3 -. 4 350.1 to 4 1.354 e 4 0.00 e 3. 8:
* 30 3.0 3.0 e 4 330.2 a-d 4 1.436 c-e 4 0.00 e 0.00 c
* 45 0.0 0.0 322.7 a-d 4 1.364 e 4 0.00 0.00. c
33 * 60 6.3 a-ß 3.0 312.9 a-ß 4 1.472 a-ß 4 0.00 e 0.00 c
45 * 15 6.3 a-ß 3.0 ß 4 326.7 a-d 4 1,373 d-ß 4 0.00 e 0.00 c
45 * 30 0.0 e 0.0 333.1 a-d 4 1.397 d-ß 4 0.00 e 0.00 c
45 * 45 0.0 0.0 e < 328.0 a-d 4 1,406 d-e 4 0.00 e 0.00 c
45 * 60 6.3 a-ß 0.0 294.3 b-f 4 1.518 a-e 4 0.00 0.00. c
60 * 15 0.0 0.0 e 4 313.5 a-e 4 1,439 c-e 4 0.00 e 0.00 c
60 * 30 0.0 3.0? '313.2 a-ß 4 1.435 c-e 4 0.00 3.13 c
60. 45 0.0 e 3.0 • v • 292.8 c-í 4 1,552 a-d 4 0.00 3.30 .- 60 * 60 0.0 3.0 264.3 £ 4 1,589 a-c 4 0.00 e 0.00 c
Square Fountain Square Square Square
Variance df Average df Average df Average df Average df Average df Average
Error of 2c 51. t 25 11.5 25 1817. 3 25 0.02 5 25 9.03 25".40
Treatment 7f 56. 1 78 12.0 78 323. 7 9 0.005 78 0.34 -9 3.13
Table 10 Inoculated with E. tenella and E. acervulina Score of Injuries Treatment Mortality Mean Psa GanaiKia Food / ear gain Cecal
PPM # Total% # DTC / or M Media # Media # Media # Media "NC 3 4 0.0 e 4; .or d 4 349.5 a 4 1,374 4 0.00 d 4 0.00 e
4 18.8 a-c 4 12.5 a 4 218.1 i 4 1867 a 4 9.00 a 4 3.48 a
Portmicina 15 4 6.3 a- * 4 3.0 d 4 271.5 c-e 4 1,671 b-d 4 4.48 b 4 2.98 D
4 0.0 e 4 0.0 d 4 328.1 a-b 4 1.455 e 4 0.44 c 4 1.56;
45 4 18.8 a-c 4 0.0 d 4 306.7 a-ß 4 1.505 c-e 4 0.06 c-d 4 0.13 e bO 4 6.3 a-e 4 3.0 d 4 339.8 a 4 1. 10 e 4 0.00 d 4 0.00 e
Example 1 | 4 12.5 a-e 4 12.5 a 4 257.6 e 4 1,729 b 4 5.00 b 4 3.69 a
4 0.0 e 4 0.0 d 4 322.9 a-c 4 1,480 d-e 4 0.19 c-d 4 1.00 d
45 4 6.3 a-e 4 0.0 d 4 304.9 a-e 4 1.455 e 4 0.00 d 4 0.00 e
60 4 0.0 e 4 0.0 d 4 297.4 a-ß 4 1.452 e 4 0.00 d 4 0.00 e
Portmicin and Example 1 15 * 15 4 0.0 e 4 3.0 d 4 342.7 to 4 1,421 to 4 0.38 c-d 4 0.25. »
-30 4 6.3 a-e 4 0.0 d 4 331.5 a-b 4 1.436 9 4 3.30 i 4 3.08 e
* 45 4 6.3 a-e 4 0.0 d 4 327.6 a-b 4 1.509 c-e 4 0.30 • i 4 0.00 e
* 60 4 6.3 a-e 4 3.0 d 4 300.2 a-e 4 1,514 c-e 4 3 00 .i 4 0.00 e
33 * 15 4 6.3 a-e 4 3.0 d 4 343.9 a 4 1.427 ^ 4 0.30 i 4 0.00
33 * 30 4 0.3 4 3.0 d 4 327.7 a-b 4 1,417 e 4 0.00 d 4 0.00 e
* 45 4 6.3 a-e 4 0.0 d 4 299.9 a-e 4 1,548 c-e 4 3.00 d 4 0.00 e
* 60 4 0.0 4 3.0 d 4 291.1 b-e 4 1,563 b-e 4 n.00 d 4 0.00 e
45 * 15 4 6.2 a-e 4 3.0 d 4 307.5 a-e 4 1,524 c-ß 4 3.30 i 4 0.00 e
45 * 30 4 0.0 e 4 3.0 d 4 330.8 a-b 4 1.385 e 4 0.00 d 4 0.00 e
45 * 45 4 12.5 a-ß 4 0.0 d 4 298.4 a-e 4 1,588 b-e 4 3.00 d 4 0.00 'e
45 * 60 4 6.3 a-e 4 0.3 d 4 295.2 a-e 4 1.507 c-e 4 3.00 d 4 0.00 e
60 * 15 4 6.3 a-e 4 3.0 d 4 314.2 a-d 4 1,497 c-e 4 3.33 d 4 0.00
60 * 30 4 0.0 4 0.0 d 4 308.5 a-ß 4 1.439 * 4 3.00 d 4 0.00 «
63. 45 4 6.3 a-e 4 3.3 d 4 309.6 a-e 4 1,432 d-e 4 3.30 i 4 0.00
63 * 60 4 18.8 a-c 4 3.0 4 262.7 d-e 4 1,696 b-c 4 3.30? 4 3.00 e
Square Fountain Square Square Square
Average df variance 1 If Media df Average df Average df Average df Average
Error of 25 143.1 25 46.2 3o6 ~ .í 25 3.35 '4 25 1 .39;? 5..3
Treatment 78 135 .; "9 lo .3: 9 47 = .. -a - - JC '7" 3; - to
Table 11 Inoculated with E. tenella and E. Maximum Injury Score
Treatment Average Mortality Weight Gain Food / Intestinal gain Cecal PPM * Total% DTC% tt Average ü Medium # Average Average 0.0 e 0.0 e 4 359.4 a 4 1.330 0.63 0.00 d
: c 43.8 to 37.5 to 4 181.0 e 4 2.198 8.50 3.83 a
Portmicin 15 6.3 b-ß 6.3 b 4 250.5 d 4 1.694 b 7.50 3.06 b
6.3 b-e 0.0 e 4 336.5 a-c 4 1.460 c-d 0.94 3.25 c-d
45 0.0 0.0 4 342.4 a-c 4 1.409 d 1.19 3 25 c-d
Í 0.0 e 0.0 e 4 337.0 a-c 4 1.398 d 0.00 3.00 i
Example I 15 o,, 0 e 0.0 e 4 260.0 d 4 1.615 b-c 4 8.44 a 3.31 b
.0 0.0 «4 321.3 a-c 4 1,387 d 4 4.06 b 0.19 c-d
45 12..5 b-c 0.0 e 4 334.3 a-c 4 1,442 c-d 4 0.00 c 0.00 d O 0..0 0.0 «4 300.1 b-c 4 1.467 c-d 4 0.25 3.00 i
Portmicin and Example 1 -5 * lb .0 0.0 354 3 a-b .379 d 0.06 - 0.00 d 15.30 0.0 0.0 353} ab .346 d 0.06 c 0.00 d .5 * 45 0.0 0.0 349 9 ac .336 d 0.00 c 0.00 d 15 * 60 0.0 0.0 307 9 ac .461 cd 0.0 000 0.00 d 30 * 15 0.0 0.0 349 8 ac .307 d 0. .1199 - 0.00 d 20 * 30 3.0 0.0 347 ac .370 d 0..0000 0.00 d 30 * 45 6.3 be 0.0 342 0 ac 1.408 to 0.0000 c 0.00 d 30 * 60 3.0 e 0.0 316 9 ac .443 cd 0.0000 c 0.00 d 45 * 15 0.0 ß 0.0 341 4 ac 1.390 d 0.00 0.00 d 45 * 30 0.0 e 0.0 334 0 ac 1.354 d 0.06 0.00 d 45 * 45 0.0 e 0.0 305.5 ac 1477 cd 1.13 0.25- cd 45 * 60 0.0 ß 0.0 293 0 1.508 cd 0.00 0.00 d 60 * 15 0.0 ß 0.0 308 .2 ac 1.481 cd 0.00 0.00 d 60 * 30 6.3 b-ß 0.0 329 2 ac 1.437 cd 0.00 0.00 d 60 * 45 12. S bc 0.0 310 4 ac 1.475 cd 0.08 0.00 d 50 * 60 6.3 be 0.0 2S3 1 to 1.673 b 0.00 0.00- d
Square Fountain Square Square Square Square Square Variation df Half df Half df Half df Half df Half df Medium
Error 326.0 25 219.5 25 6792.7 3.126 25 28.51 25 .98 Treatment 52.1 79 14.0""? 438.2 3,007 -3 0.48"3 .0o Table 12 Inoculated with E. tenella and E. acervulina Injury Score
Treatment Mortality Medium Gain of Poso Alimentaganancia Intestinal Cecal
PPM? Total% DTC% 4 Average «Mediate tf Average # Media
NC 4 0.0 to 4 3.0 to 4 291.6 to 4 1,438 b-c 4 0.00 b 4 0.00 b
And 4 12.5 to 4 6.3 to 4 203.2 c 4 1.989 to 4 -.94 to 4 3.33 a
Portmicin and Example 1 15 * 15 0.0 to 4 0.0 to 4 279.8 to 4 1.391 b-c 4 0.00 b 4 0.00 b
* 20 0.0 to 4 0.0 to 4 290.0 to 4 1.447 b-c 4 0.00 b 4 3.19 b
* 25 0.0 to 4 0.0 to 4 278.2 to 4 1,428 b-c 4 0.00 b 4 0.00 b
* 30 0.0 to 4 0.0 to 4 282.7 to 4 1.372 b-c 4 0.00 b 4 0.13 b
. 35 6.3 to 4 3.0 to 4 268.3 to 4 1.415 b-c 4 0.00 b 4 0.00 b
40 * 40 0.0 to 4 0.0 to 4 258.6 a-b 4 1.433 b-c 4 0.00 b 4 0.00 b
. 10 0.0 to 4 0.0 to 4 279.6 to 4 1.364 b-c 4 0.06 b 4 0.00 b
26. 7 * 13.3 6.3 to 4 0.0 to 4 291.5 to 4 1.393 b-c 4 0.00 b 4 0.00 b
33. 4 * 16.7 6.3 to 4 3.0 to 4 230.3 4 1.315 b-c 4 0.00 D 4 3.00 b
40 * 20 0.0 a 4 0.0 a 4 253.6 a-o 4 1.471 b-c 4 0.00 4 0.00 b
46. 7-23.3 0.0 a 4 0.0 a 4 252.4 a-D 4 1.446 b-c 4 0.30 b 4 0 00 b
53. * 26.5 0.0 to 4 0.0 to 4 219.9 a-b 4 1.644 b 4 0.00 b 4 0.00 b
22. 5 * /. 5 0.0 to 4 0.0 to 4 292.9 to 4 1.311 r 4 3.00 0 4 C 00 t
* 10 3.0 to 4 1.0 to 4 236.1 4 1.363 b-c 4 3.00 b 4 3.06 b
37. 5 * 12.5 3.0 to 4 3.0 to 4 270.9 to 4 1.376 D-C 4 0.30 b 4 0.00 or
45. 15 0.0 to 4 0.0 to 4 -.404 b-c 4 0.00 b 4 0.00 b
52. 5.17.5 3.0 a 4 c.o a < 263 *. '7 a-b 4 1.407 b-c 4 0.00 c 4 3.30 t or 3.20 0.0 a 4 0.0 a 4 234. "a-D 4 .1.565 b-c 4 0.00 0 4 j.00 b
Square Fountain Square Square Square
Vari ounce df Media df Average df Average df Average r Average df ..Mí ?! '?
17-.rtr Af 19 47.3 19 .3 .3 2344.5 19 3.388 39 12.59 39 2.21 Treatment 60 33.9 60 7.8 b0 301. s 60 0.016 oO 0.00 60 0.02 IflbJaJ3 Inoculated with E, tenella and E. acervulina Score of Injuries
Treatment Average Mortality Weight Gain Food / gain Cecal Intestinal
PPM # Total% # DTC% Media U Media H Media H Medía
NC 0 4 0.0 to 4 0.0 to 316.3 to 1.299 c 4 0.00 c 4 0.00 f
IC 0 4 12.5 a 4 12.5 a 196.6 b 1.803 a 4 7.63 a 4 3.69 a
Portmicin and Example 1 15.15 4 12.5 to 4 6.3 to 315.9 to 1.374 b-c 4 2.33 b 4 3.08 a-b
. 20 4 0.0 to 4 0.0 to 319.2 to 1,304 c 4 0.44 c 4 1.19 d-f
* 25 4 0.0 to 4 0.0 to 313.0 to 1.310 c 4 0.06 c 4 0.38 f
* 30 4 6.3 to 4 0.0 to 311.0 to 1.328 b-c 4 0.00 c 4 0.00 f
* 35 4 0.0 to 4 0.0 to 322.3 to 1.370 b-c 4 0.00 c 4 3.00 £
40 * 40 4 0.0 to 4 0.0 to 306.3 to 1.314 c 4 0.00 c 4 0.00 f
* 10 4 6.3 to 4 0.0 to 298.5 to 1.394 b-c 4 2.06 b 4 2.94 a-b
26. 7 * 13.3 4 0.0 to 4 0.0 to 312.8 to 1.310 c 4 0.38 c 4 1.81 c-e
33. 4 * 16.7 4 0.0 to 4 0.0 to 328.9 to 1.323 b-c 4 0.13 c 4 0.19 £
40 * 20 4 6.3 to 4 3.0 to 306.1 to 1.335 b-c 4 0.06 c 4 0.35 f
46. 7.23.3 4 0.0 to 4 3.0 to 308.8 to 1.348 b-c 4 3.06 4 3.13 £
53. 4 * 26.6 4 0.0 to 4 3.0 to 308.8 to 1.317 b-c 4 0.00 4 0.00 f
22. 5 * 7.5 4 0.0 to 4 3.0 to 287.9 to 1,504 b 4 2.63 b 4 3.38 a
* 10 4 0.0 to 4 0.0 to 325.3 to 1.321 b-c 4 0.69 c 4 2.31 b-c
37. 5 * 12.5 4 3.0 to 4 0.0 to 299.6 to 1.364 b-c 4 0.31 c 4 2.13 b-d
45 * lS 4 0.0 to 4 0.0 to 323.0 to 1.292 c 4 0.13 c 4 1.00 e- £
52. 5 * 17.5 4 0.0 to 4 0.0 to 308.6 to 1.377 b-c 4 0.00 c 4 0.00- £
60 * 20 4 0.0 to 4 0.0 to 300.5 to 1.317 b-c 4 0.06 c 4 0.00 £
Square Fountain Square Square Square
Variety df Media df Media df Media df Media df Media df Media
Error of 19 0.3 19 37.4 19 3028.1 19 0.053 19 12.91 19 7.06
Treatment 60 65.1 60 39.1 60 523.0 60 0.006 60 0.20 60 0.31 Table 14 Inoculated with E. tenella, E. acervulina and E. Maximum Injury Score
Treatment Average Mortality Weight Gain Food / gain Cecal Intestinal
PPM n Total% # DTC% U Average # Average H Average Media
NC 0 4 12.5 to 4 0.0 to 306.6 to 4 1.456 to 4 0.00 r 4 0.00 e
: c 0 4 6.3 to 4 0.0 to 291.7 to 4 1.454 to 4 5.88 a-c 4 2.81 a-b
Portmicin and Example 1 15 * 15 0.0 to 4 0.0 to 299.4 to 4 1.388 to 4 4.69 a-d 4 1.75 b-d
* 20 0.0 to 4 0.0 to 309.1 to 4 1.355 a 4 4.19 a-e 4 2.00 a-c
. 25 0.0 to 4 0.0 to 281.4 to 4 1.434 to 4 1.44 e- £ 4 0.25 d-e
. 30 0.0 to 4 0.0 to 312.9 to 4 1.390 to 4 2.00 d-f 4 0.44 c-e
. 35 6.3 to 4 0.0 to 306.4 to 4 1,400 to 4 1.29 e- £ 4 0.31 d-e
40. 40 0.0 to 4 0.0 to 300.0 to 4 1.359 to 4 1.13 e-f 4 0.00 e
* 10 6.3 to 4 0.0 to 301.3 to 4 1,421 to 4 2.60 d-f 4 2.00 a-c
26. 7.13.3 6.3 to 4 0.0 to 300.1 to 4 1.485 to 4. 3.69 b-ß 4 2.71 a-b
33. 4.16.7 0.0 to 4 3.0 to 312.0 to 4 1.338 to 4 3.94 b-e 4 1.56 b-e
40. 20 0.0 to 4 3.0 to 310.3 to 4 1.362 to 4 2.31 d- £ 4 0.69 c-e
46. 7.23.3 6.3 to 4 3.0 to 305.0 to 4 1.383 to 4 2.46 d- £ 4 0.54 c-e
53. 4 * 26.6 0.0 to 4 0.0 to 303.3 to 4 1,420 to 4 2.31 d-f 4 0.56 c-e
22. 5-7.5 0.0 to 4 3.0 to 271.o to 4 1.493 to 4 6.69 to 4 2.94 a-b
* 10 0.0 to 4 3.0 to 301.6 to 4 1.413 to 4 6.31 a-b 4 3.33 a
37. 5.12.5 0.0 to 4 3.0 to 283.4 to 4 1.485 to 4 3.63 b-e 4 2.38 a-b
45. 15 6.3 to 4 3.0 to 234.1 to 4 1.415 to 4 3.17 c-e 4 1.63 b-d
52. 5.17.5 12.5 a 4 3.0 a 307.1 a 4 1.459 a 4 2.90 d-f 4 0.88 c-e 0 0. 0 0.0 a 4 3.0 a 293.1 a 4 1.364 a 4 1.88 d-f 4 3.56 c-e
Square Fountain Square Square Square
Variety if Media df Media df Media df Media df Media df Media
Error of 19 74.0 19 0.0 19 516.0 19 0.009 19 12.65 19 4.65
Treatment 60 39..5 60 3.0 60 ol0.9 oO 0.010 60 1.64 60 3.45 Table 15 Inoculated with E. tenella and E. maxim Score of Injuries
Treatment Average Mortality Weight Gain Food / gain Cecal Intestinal
PPM n Total% tt DTC% # Media ti Media H Average # Media
NC 0 4 0.0 0 4 0.0 b 4 326.7 a 1.415 b 4 0.13 c 0.00 i xc 0 4 25.0 a 4 25.0 a 4 185.1 b 2.283 a 4 9.13 a 3.81 a
Portmicin and Example 1 15.15 4 0.0 b 4 0.0 b 4 308.6 a 1.414 b 4 0.94 Z 0.81 d
. 20 4 0.0 b 4 0.0 0 4 324.2 to 1.417 b 4 0.00 c 0.00 d
. 25 4 3.0 b 4 3.0 0 4 315.4 to 1.378 b 4 0.00 c 0.00 d
. 30 4 0.0 b 4 0.0 b 4 304.4 a 1.416 b 4 0.00 c 0.00 a
. 35 4 0.0 b 4 3.0 D 4 305.0 to 1.460 b 4 0.00 c 0.00 j
40 * 40 4 • 3.0 b 4 0.0 b 4 296.5 to 1.429 b 4 0.00 c 0.00 d
* 10 4 0.0 b 4 0.0 b 4 323.2 a 1.415 b 4 1.25 c 1.81 b
26. 7.13.3 4 3.0 b 4 3.0 D 4 297.3 to 1.446 b 4 0.56 c 0 25 d
33. 4 * 16.7 4 6.3 D 4 3.0 £ 4 308.4 to 1.512 b 4 0.63 c 0.00 d
40. 20 4 3.0 D 4 3.0 b 4 300.4 to 1,409 b 4 0.06 c 0.00 J
46. 7.23.3 4 3.0 b i 3.0 D 4 303.7 to 1.475 b 4 0.00 0.30 d
53. 4 * 26.6 4 3.2 t 4 3.0 c 4 291.3 a 1.505 b 4 0.00 c 0.00 d
22. 5 * 7.5 4 3.0 b * 0 4 294.8 to -.493 D 4 3.44 b '1!
* 10 4 ^. z 4 3.0 D 4 314.4 to 1.395 D 4 0.31 - 0.06 i
37. 5 * 12.5 4 3.0 c 4 3.3 .0 4 293.2 to 1.507 b 4 3.13 3.00 j
45 * 15 4 3.3 b 3.0 4 314.2 to 1.479 b 4 3.00 Z 0.30 c
52. 5 * 17.5 4 3.0 b 3.0 b 4 302.3 a 1.450 b 4 0.06 0.00 d
60 * 20 4 3.0 ¿- 3.3 b 4 231.3 a 1.522 b 4 0.31 0.00?
Square Fountain Square Square Square
Variance df Average df Average df Average df Average df Average df Average
Error of 19 129. S 39 19 3452.9 19 0.147 19 17.7; 19 3.58
Treatment 60 28.6 oO 23.8 bO 467.7 60 3.019 oO 3.43 bO 3.11 Table 16 Inoculated with E. te ella and E. maxim Score of Injuries
Treatment Average Mortality Weight Gain Food / gain Cecal Intestinal
PPM tt Total% # DTC% # Media tt Media # Media »Media
NC 3 4 3.0 to 4 3.0 a :: - 7th to 4 1,296 4 3.30 z • * 3. 0 d
Ó "4 0.0 a 4 3.0 a 4 245.3 c 4 1.808 a 4 3.00 a 4 3.63 a
Port ictna and Example 1 15 * 15 4 0.0 to 4 0.0 to 290.5 a-c 4 1.535 a-b 4 1.75 4 2.81 a-b
* 20 4 0.0 to 4 3.0 to 300.4 a-c 4 1.449 b 4 0.7 ~ 4 3.75 i
* 25 4 0.0 to 4 3.3 to 334.5 to 4 1.370 b 4 0.06 z 4 0.44 d
* 30 4 0.0 to 4 3.3 to 318.6 a-D 4 1,500 b 4, .00 z 4 0.30 d
* 35 4 0.0 to 4 3.3 to 301.1 a-c 4 1.516 a-b 4 0.30 z 4 0.13 i
40 * 40 4 0.0 a 4 3.0 a 298.6 a-c 4 1.547 a-D 4 3.30 - 4 3.19 1
* 10 4 6.3 to 4 6.3 to 288. i a-c 4 1,560 a-c 4 2.13: 4 2.83 a-D
26. 7.13.3 4 6.3 a 4 3.0 a 302.9 a-c 4 1.582 a-D 4 1.50.: 4 2.98 a
33. 4.16.7 4 3.0 to 4 3.0 to 324.7 a-b 4 1.443 c 4 3.33 4 3.33 d
40. 20 4 0.0 to 4 3.3 to 331.2 to 4 1.392 b 4 3.00: 4 0.31 i
46. 7-23.3 4 0.0 a 4 3.3 a 297.6 a-c 4 1,572 a-b 4 3.00 z 4 0.19 d
53. 4.26.6 4 3.0 a 4 3.0 a 265.3 b-c 4 1 641 a-b 4 3.00 -. 4 0.00 i
22. 5.7.5 4 3.0 to 4 3.0 to 296.0 a-c 4 1,548 a-b 4 5.30 b 4 3.63 a
* 10 4 3.0 to 4 3.C to 330.3 a-c 4 1.519 a-b 4 2.50; 4 2.50 a-b
37. 5 * 12.5 4 3.3 a 4 3.3 a 323.2 a-o 4 1.436 b 4 3.30 - 4 1.81 b-c
45 * 15 4 3.0 a 4 3.0 a 297.0 a-z 4 -.537 a-o 4 2.13; 4 1.36 c-d
52. S.17.5 4 0.0 to 4 3.0 to 7.; a-c 4 1.587 a-b 4 3.00 4 3.13 -j
60 * 20 4 6.3 to 4 3.0 to 276.2 a-c 4 1,637 a-b 4 3.00 4 0.00 d
Square Fountain Square Square Square
Variance df Average df Average df Average df Average df Average df Average
Error of 19 21.3 19".9 19 2284. i 19 3.04 2 19 1-.09 19 7.32
Treatment 00 23.4 63 -.3 oO 561.) oO 0.01 5 bO 1.14 60 3.33 Table 17 Inoculated with E. tenella, E. Acervulina and E. maxim Score of Injuries
Treatment Average Mortality Weight Gain Food / Gut Gain Cecal PPM # Total% # DTC »/« tt Average H Average tt Average tt Average
NC '- "" 0 4 0.0 to 4 0.0 to 328.8 to 1.455 to 4 0.31 e 4 0.00 d
0 4 0.0 to * 0.0 to 265.8 to 1.715 to 4 7.56 to 4 3.50 a
Portmicin V Example 15 * 15 4 0.0 to 4 0.0 to 284.7 to 1.610 to 4 5.38 a-d 4 2.25 b
* 20 4 0.0 to 4 0.0 to 321.4 to 1.523 to 4 3.50 b-e 4 1.25 c-d
* 25 4 6.3 to 4 0.0 to 310.3 to 1.682 to 4 2.69 c-e 4 0.48 d
* 30 4 0.0 to 4 0.0 to 334.9 to 1.438 to 4 2.56 c-e 4 0.13 d
* 35 4 0.0 to 4 0.0 to 315.9 to 1.557 to 4 1.31 e 4 0.13 d
40 * 40 4 6.3 to 4 0.0 to 321.8 to 1.558 to 4 1.25 e 4 0.19 d
* 10 4 6.3 to 4 o.o to 284.1 to 1.667 to 4 6.63 a-b 4 2.83 a-b
26. 7.13.3 4 0.0 to 4 0.0 to 302.2 to 1.589 to 4 6.00 a-c 4 2.44 a-D
33. 4 * 16.7 4 0.0 to 4 0.0 to 313.0 to 1.543 to 4 3.81 b-ß 4 0.75 d
40 * 20 4 0.0 to 4 0.0 to 320.6 to 1.436 to 4 2.69 c-e 4 0.19 d
46. 7-23.3 4 0.0 to 4 0.0 to 317.1 to 1.450 to 4 1.75 e 4 0.31 d
53. 4.26.6 4 0.0 to 4 3.0 to 286.7 to 1.553 to 4 1.63 e 4 0.13 d
22. 5.7.5 4 6.3 to 4 0.0 to 299.8 to 1.667 to 4 5.21 a-d 4 2.50 a-b
* 10 4 6.3 to 4 3.0 to 275.2 to 1.695 to 4 6.17 a-b 4 2.54 a-b
37. 5 * 12.5 4 6.3 to 4 0.0 to 295.6 to 1.656 to 4 5, b5 to-c 4 1.73 b-c
45 * 15 4 6.3 to 4 3.0 to 320.1 to 1.517 to 4 2.88 c-e 4 O.o5 i
52. 5 * 17.5 4 0.3 to 4 3.0 to 315.7 to 1.592 to 4 2.08 d-e 4 0.25 d
60 * 20 4 0.0 to 4 3.0 to 277.7 to 1.772 to 4 2.00 d-e 4 0.13 d
Square Fountain Square Square Square Square
Variance if Media df Average dr Average r Medium df Average df Average
Error of 19 39.5 19 3.0 19 1563.8 19 0.036 19 17.71 19 5.28
Treatment 60 62.5 60 0.0 60 745.8 bO 0.018 60 2.19 60 0.30"Table 18 Inoculated with E. tenella and E. maxim (Control uninfected in this experiment) Injury Score
Treatment Average Mortality Weight Gain Food / gain Cecal Intestinal
PPM # Total% n DTC / o tt Media tt Media tt Media tt Media
NC 3 3.0, - 3.0 < 250.9 a. 1,361,. 0.30 0.00
Example 5 5 1 25.0 e 25.0 d 151.5 h 1.811 d 9.00 b 1 3.50 b
Example 4 50 25.0 I 25.0 d 159.1 9 1 1.905 c 9.00 b 3.50 b
100 1 0.0 i 0.0 1 215.6 c 1 1,480 h 3.75 £ 2.00 f
Example 3 50 1 0.0 1 1 0.0 206.6 d 1 1.502 3 5.50 2.50 *
100 1 100.0 a 1 25.0 d 0 0.0 1 9.980 a 2.30 1 0.00 - Example 1 50 1 0.0 i. 0.0 1 226.1 b 1 1.446 1 1.00 1.50 g
100 1 25.0 e 1 3.0 1 1 196.2 f i 1.305 e 0.30 0.67 Example 6 50 1 25.0: 25.0 d 1 1 * 8.9 i 1.905 c 8.50 3.25 c
100 1 0.0 _ 0.0 3 1 199.4 e * 1,577 £ 7.25 d 2.50 e
Square Fountain Square Square Square
Variance df Media df Average df Average df Media di Media df Average
Error of 5 944.4 9 166.7 9 3843.9 9 6.990 9 13.94 1.84
Treatment 0 0.0 0 0.0 0 0.0 0 0.000 0 3.30 or 0.00 Table 19 Inoculated with E. tenella, E. acervulina and E. Maximum Score of Lesions
Treatment Average Mortality Weight Gain Food / gain Cecal Intestinal
PPM tt Total% tt DTC%? M dia tt Media tt Media tt Media
NC 0 0.0 to 4 0.0 to 4 312.7 to 4 1.334 d 4 0.00 c 4 0.00 e
CI 0 6.3 a 4 6.3 a 4 169.3 c 4 2.146 a 4 8.94 a 4 3.44 a-b
Example 10 18 0.0 to 4 0.0 to 4 175.7 c 4 1.920 b 4 8.81 to 4 3.63 a
36 0.0 to 4 0.0 to 4 218.6 b 4 1.691 c 4 8.31 to 4 2.50 c
54 0.0 to 4 0.0 to 4 275.3 to 4 1.481 d 4 5.13 b 4 1.56 d
72 0.0 to 4 0.0 to 4 232.4 to 4 1.417 d 4 0.94 c 4 0.50 e
Example 1 18 0.0 a 4 0.0 a 4 192.1 b-c 4 1837 b-c 4 8.38 a 4 2.69 b-c
36 0.0 to 4 3.0 to 4 273.4 to 4 1.396 d 4 1.75 c 4 0.81 d-e
54 0.0 to 4 0.0 to 4 276.4 to 4 1.357 d 4 0.00 c 4 0.44 e
72 0.0 to 4 0.0 to 4 270.8 to 4 1.458 d 4 0.13 c 4 0.13 e
Square Fountain Square Square Square
Variation df Average df Average df M dia df Average df Average df Mcdiu
Error of 9 15.6 9 15.6 9 10390.9 9 0.313 9 67.47 9 7.72
Treatment 30 15.6 33 15.6 30 416.2 30 0.014 30 1.28 30 0.27
Table 20 Inoculated with E. tenella and E. Maximum score of the lesions
Treatment Average Mortality Weight Gain Alimento Intestinal Ear Gain
PPM H Total% U DTC% H Average tt Average tt Average _ # Average
NC 0 4 6.3 to 4 3.0 to 4 325.4 to 4 1,444 c 4 0.00 i 4 0.00 i
IC 0 4 25.0 a 4 25.0 a 4 193.3? 4 2.022 a 4 5.81 a-b 4 3.81 a
Example 1 15 4 18.8 a 4 12.5 a 4 204.6 -i 4 1.909 a-b 4 7.00 a 4 4.00 a
4 0.0 to 4 0.0 to 4 271.4 a-d 4 1.529 4 2.50 c 4 2.44 t
45 4 0.0 to 4 0.0 to 4 296.9 a-c 4 1,466 c 4 0.19 i 4 0.31 i
Salinomycin 22 4 12.5 to 4 6.3 to 4 241.1 c-e 4 1,669 a-c 4 4.S3 b 4 3.63 a
44 4 12.5 a 4 12.5 a 4 248.9 b-e 4 1,749 a-c 4 3.25 c 4 3.o9
Salinomycin + Example 1 22 * 15 4 12.5 to 4 12.5 to 4 270.8 a-d 4 1,700 a-c 4 2.69 c 4 3.S6 a
22. 30 4 6.3 to 4 0.0 to 4 296.9 a-c 4 1.490 c 4 0.00 d 4 1.23 r *
22 * 45 4 6.3 to 4 0.0 to 4 292.1 a-c 4 1.473 c 4 0.00 d 4 0.08 d
Sálinomycin. Examplß 1 44 * 15 4 0.0 a 4 0.0 a 4 312.0 a-b 4 1,439 c 4 0.13 d 4 2.50 b
44 * 30 4 6.3 to 4 0.0 to 4 318.3 to 4 1,448 c 4 3.30 d 4 0.54 d
44. 45 4 0.0 to 4 0.0 to 4 305.3 a-c 4 1.404 c 4 3.00 d 4 0.25 d
Salinomycin U < 12.5 to 4 12.5 to 4 218.4 d-e 4 1.918 a-b 4 6.63 to 4 3.5o a
Salinomycin + Example 1 11 * 15 4 25.0 a 4 25.0 a 4 263.7 a-d 4 1,688 a-c 4 4.56 b 4 3.94 a
11 * 30 4 6.3 to 4 0.0 to 4 287.2 a-c 4 1.596 b-c 4 0.38 to 4 1.60 z
11 * 45 4 0.0 to 4 0.0 to 4 3? L.7 a-D 4 1,522 c 4 0.00 d 4 0.00 d
Square Fountain Square Square Square
Variance df Average df Average df Average df Average df Average df Average
Error of j, 274.6 16 312.5 16 o369.2 16 0.146 16 27.27 16 10.56
Treatment 51 226.7 51 156.3 51"94.6 51 0.02 S 51 3.59 1 3 13 4
Table 21 Inoculated with E. tenella and E. acervulina Injury Score
Treatment Average Mortality Weight Gain, < Cecal Intestinal gain / gain
PPM U Total% U DTC0 / »# Media # Media H Average _ tt M dia
NC 0 2 0.0 b 2 3.0 a 2 300.6 a 2 1,371 d 2 0.00 c 2 3.30 -.
IC 0 2 12. S b 2 12.5 a 2 165.7 b-c -) 1,974 b 2 0.13 a 2 3, o3 c
Example 1 12.5 2 25.0 D 12.5 ¿210.7 a-b 2 1.740: 4.21 b ¿4.00 c
2 0.0 b 3.0 a 2 275.6 a • > 1.374 d 2 0.25 c 2 2.25 t
50 2 3.3 0 2 0.0 a _. 291.2 to 2 1,381 d • > 0.00 2 0.63
100 1 50.0 to 1 3.0 to 115.8 c 1 3,416 to 1 0.30 1 0 00 1
Example 18 2 12.5 _, - 12.5 a 2 219.4 a-b 2 1,598 c-d - > 5.75 to 3. "1
2 0.0 2 3.3 to 2 .292.4 to 2 1.361 d 3.13 c 2 0.75
50 • 3.0 C - J.3 a 2 242.9 a-D 2 1,526 c-d 2 0.00 c 2 0.00:
Square Fountain Square Square Square
Variance df Average df Average df Average df Average df Average df Average
Error of 8 381.4 3"5.8 9 6198.6 8 0.500 9 14.12 9 5.69
Treatment 8 78.1 3 3 636.4 9 0.007 9 3.11 3 0.15
Tabia Í Inoculated with E. tenella, E. acervulina and E. Maximum Injury Score
Treatment Average Mortality Weight Gain Alimentaganancia Intestinal Cecal PPM tt Total% tt DTC% tt Average tt Average H Average tt Average
NC 0 305. "to 4 1,374 .00 0.33 IC or 0.0 h .247.0 e-fl 4 1,549 af 4 .50 ac 4 2.50 a- Example 1 15 0.0 0.0 256.2 bh 4 1,525 an 4 9.81 a 4 1.88 b- 30 0.0 0.0 266.3 ah 4 1.489 ah 4 5.63 c- £ 4 0.13 45 3.0 n 3.0 73.2 ah 4 1.42? Bn 4 3.31 di 4 0.00 Portmicina 6.3 an JO h 241.8 gn 4 1.635 a 4 3.69 a 4 3.56 a
4 3 3 .. .00 h 3.0 h 269.0 an 4 1.438 ah 4 6.31 bd 4 2.63 a- 45 4 00. .00 n 0.0 h 258.6 an 4 1561 a 4".63 ac 4 1.75 b- Salinomycin 15 4 6 .3 ah 0.0 245.4 fh 4 1.603 ac 4 9.17 ab 4 3.06 a
4 3, .0 n - .0: 39.3 h 4 1,638 a-b 4 3.25 a-ß 4 3.56 a
45 4 3 .0 0.0 ..55.8 c-h 4 1,562 a-e 4 b.31 b-d 4 2.88 a- Portmicin + Example 1 1S * 15 4. J a-n a-n 1.492 a-h .00 d-g 3.69 d- 15 * 30 4 0 0 .. .00 h 262 a- 1.523 a-n .44 ß-3 3.30
* 45 4 ó6 .., 33 a-h 251 d-h 1,544 a-g .50 9-3 3.06
* 15 4 00 .. .00 275 a-h 1.447 a-h .06 d-h 0.06
* 30 4 ó6. .33 268 a-h 1.454 a-h .75 n-k 0 00
. 45 4 ó6 ..33 a-n 233 a-e 1,430 a-h 0.00
45. 15 4 00 .. .00 h 292 a- £ 1,401 f-h .31 g-j 0.30
45. 30 4 00 ..00 h 6 a-h 1.420 e-h .69 h-K 0.30
4S.45 4 3 ..33 h 2'8 a-h 1.429 a-h .13 j-lc 0.30
Salinomycin + E Ejjeerm nppll Oo 1 15.15 4 0 0 ..33 a-n .. 440 a-h 5.81 c-e 1.-5
. 30 3.0 232 a-c .. 394 g-n 4.44 d-g 0.31 15.45 3.0 3.0 274 a-h .423 d-h 3.31 ß-3 0. C 0
. 15 3.3 292 a-g .529 a-n 4.75 i- < 1.33 33-30 3.3 269 an 1.453 an: • .13 3.30 30.45 3.3 276 an 1.435 ah 1.06 3- 0.33 45 * 15 o.3 a-fi 3.3 294 a or 1.425 cn 4.15 dh 45.30 3.3 264 ah 1.438 ah i.SC; - '3.C6 45.45 12.5 a 23S ad 1.441 an 0.83 jk 3.30
Square Fountain Square Square Square Square Square Vari ounce df Half df Half df Half df Medium df Medium df Medium Error of 28 4S.8 28 5.4 28 1048.4 23 0.023 28 27.90 28 6.17
Treatment 87 44.9 87 5.4 37 350.9 87 0.009 37 1.20 87 0.30 Table 23 Inoculated with E. tenella, E. acervulina and E maximum Injury Score
Treatment Mortality Means Weight Gain Food / Earnings Intestinal Cecal gPM tt Total% # DTC% tt Average tt Average tt Average # Media
NC 0 0.0 h 4 0.0 a 4 311.1 a 4 1.331 b-g 4 0.00 i 4 0.00 c
IC 0 0.0 h 4 3.0 a 4 240.6 f-h 4 1,538 b-e 4 9.44 a 4 2.88 a- Example 1 15 0.0 h 4 3.0 a 4 250.2 c-g 4 1,561 b 4 9 88 a-b 4 3..9 a
0.0 h 4 0.0 a 4 271.3 a-g 4 1.412 b-g 4 ß. ß3 c-d 4 0.31 c
45 3.0 n 4 0.0 a 4 257.4 b-g 4 1540 b-d 4 3.31 f-h 4 0.31 c
Porcmicin 15 0.0 h 4 0.0 a 4 207. h 4 1.912 a 4 9.38 a 4 3.50 a
3.0 h 4 3.0 a 4 252.9 b-g 4 1,522 b-g 4 3.00 a-c 4 2.44 a- 45 0.0 n 4 3.0 a 4 244.1 e-h 4 1,539 b-e 4 7.06 b-d 4 1.13 c
Salinomycin? N 15 6.3 a-a 4 3.0 a 4 228.6 g-h 4 1,837 a 4 8.92 a-b 4 3.10 a
0.0 h 4 3.0 a 4 255.9 b-g 4 1,522 b-g 4 9.44 a-c 4 3.33 a
45 3.0 h 4 3.0 a 4 245.4 d-h 4 1526 b- £ 4 8.06 a-c 4 2.50 a- Portmicina + E | 4 implo 1 15.15 3.0! -. 4 3.0 a 4 286.9 a- £ 4 1,410 b-g 4 4.63 e-f 4 0.38
. 30 3.0 h 4 3.0 a 4 304.8 a-b 4 1,320 e-g 4 2.88 f-h 4 0.00"
. 45 6.3 a-d 4 3.0 a 4 279.1 a-f 4 1.444 b-g 4 1.19 h-i 4 0.00 c
* 15 0.0 h 4 0.0 to 4 2. a-g 4 1.389 b-g 4 2.44 g-h 4"0.00 c
. 30 3.0 h 4 3.0 a 4 299.2 a-c 4 1.339 b-g 4 2.13 h-i 4 0.06 c
* 45 3.0 h 4 3.0 a 4 298.9 a-c 4 1,320 e-g 4 1.56 h-i 4 0.00 c
45. 15 6.3 a-d 4 3.0 a 4 271.0 a-g 4 1419 b-g 4 2.35 g-h 4 0.00 c
45. 30 0.0 h 4 0.0 a 4 293.5 a-e 4 1.387 b-g 4 1.31 h-i 4 0.19 c
45. 45 0.0 h 4 0.0 a 4 283.1 a-f 4 1.326 c-g 4 1.56 n-i 4 '0.00 C
Salinomycin * Example 1 15.15 0.0 n 4 3.0 a 4 264.5 a-g 4 1490 b-g 4 5.81 d-e 4 2.36 b
. 30 0.0 h 4 3.0 a 4 298.0 a-f 4 1,380 b-g 4 4.09 e-f 4 0.38 c
. 45 3.3. 4 3.0 a 4 301.3 a-c 4 1.338 b-g 4 2.06 h-i 4 0.00 '- 30.15 0.3 h 4 3 3 a 4 289.5 a-í 4 1.382 b-g 4 4.44 e-g 4 1.98 b
* 30 3.0 1 4 3 0 a 4 276.6 a-g 4 1470 b-g 4 3 13 f-h 4 3.2
* 45 o.3 a-d 4 3.0 a 4 291.3 a-f 4 1.391 b-g 4 i. h-i 4 3.00 c
45 * 15 0.0 n 4 3.0 a < 335.9 a-b 4 1.295 3 •) 3.13 f-h 4 0.75:
45 * 30 0.0 h 4 0.0 a 4 297, b a-d 4 1.306 f-g 4 2.06 h-i 4 0.0b
45 * 45 0.0 n 4 0.0 a 4 291.4 a-f 4 1.413 b-g 4 1.00 h-i 4 0.19 0
Square Fountain Square Square Square
Variety df Media df_ Media df Media df Media df Media _ df Meclni
Error of 26 19.2 29 3.0 28 3628.9 23 0.082 29 3o .2 5 23 6 41
Treatment 37 21. b 3? : .o 37 407.- 87 J .01 3 = 7 3.95 3 '3.2b
Table 24 Inoculated with E. tenella, E. acervulina and E. Maximum score of the lesions
Treatment Average Mortality Weight Gain Food / gain Cecal Intestinal
PPM tt Total% # DTC% It Media tt Media # Media II Modin
NC 3 4 0.0 h 4 0.0 h 4 333.2 a 4 1.304 g-h 4 0.00 k 4 0 00 e re 0 4 0.0 h 4 0.0 h 4 270.6 f-h 4 1.469 a-b 4 7.88 a 4 2 56 a-D
Example 18 15 4 0.0 h 4 0.0 n 4 277.5 d-h 4 1.426 a-h 4 7.94 a 4 1.50 c
4 6.3 a-d 4 0.0 n 4 303.4 a-h 4 1.347 a-h 4 4.63 b-d 4 3.00 e
45 4 0.0 h 4 0.0 h 4 298.7 a-h 4 1,317 d-h 4 2.56 e-i 4 0.00 e
Example 1 15 i 6.3 a-d 4 6.3 a 4 280.1 b-h 4 1.436 a-g 4 7.13 a 4 2.06 b
4 0.0 h 4 0.0 h 4 294.3 a-h 4 1.392 a-h 4 7.00 a 4 0.13 d-e
45 4 0.0 h 4 0.0 h 4 300.9 a-h 4 1.327 a-h 4 3.69 c-f 4 0.30 e
Portmicin 15 4 0.0 h 4 0.0 h 4 277.8 c-h 4 1.462 a-c 4 8.06 a 4 2.44 a-b
4 0.0 h 4 3 0 h 4 264 8 h 4 1.485 a 4 7.94 a 4 2.94 a
45 4 0.0 h 4 j.0 h 4 276.- e-h 4 1.436 a-g 4 5.63 b 4 1.25 c
Portmicin + Example 18 15 * 15 4 0.0 h 4 0.0 n 4 305.0 a-h 4 1,377 a-h 4 4.69 b-d 4 0.38 d-e
* 30 4 0.0 h 4 0.0 h 4 211.1 a-ß 4 1,340 a-h 4 3.25 d-g 4 0.00 e
* 45 4 0.0 h 4 3.0 n 4 307.9 a-f 4 1.349 a-h 4 1.56 g-k 4 0.00 e
* 15 4 0.0 h 4 3.0 n 4 301.9 a-h 4 1.333 a-h 4 3.94 b-ß 4 0.25-d-e
. 30 4 3.0 h 4 3.0 h 4 298.3 a-h 4 1.384 a-h 4 1.50 g-k 4 0.06 d-ß
. 45 4 0.0 h 4 0.0 h 4 289 6 a-h 4 1.394 a-h 4 0.88 h-k 4 0.00 e
45. 15 4 6.3 a-d 4 3.3 .-, 4 313 9 a-d 4 1,312 e-h 4 2.25 e-j 4 0.00 e
45. 30 4 C.O h 4 0.3 h 4 304 5 a-h 4 1.306 f-h 4 1.13 g-k 4 0.00 e
45. 45 4 0.0 h 4 0.0 n 4 265 6 g-h 4 1,450 a-d 4 0.19 3-k 4 0.00 e
Portmicin + Example 1 15 * 15 4 6.3 a-d 4 3.3 n 4 316.2 a-b 4 1,296 h 4 5.31 b-c 4 0.50 d
* 30 4 0.0 h 4 3.0 4 305 9 a-h 4 1,332 a-h 4 2.94 d-h 4 0.00 e
* 45 4 0.0 h 4 0.0 h 4 295 4 a-h 4 1.343 a-h 4 1.94 ß-k 4 0.00 e
* 15 4 0.0 h 4 0.0 n 4 206 5 a-g 4 1,317 d-h 4 3.30 d-h 4 0.00 e
* 30 4 0.0 h 4 0.0 h 4 305 8 a-h 4 1.323 b-h 4 1.31 £ -k 4 0.13 d-e
* 45 4 0.0 4 3.0 h 4 304 7 a-h 4 1.365 a-h 4 1.56 g-k 4 0.00 e
45 * 15 4 0.0 h 4 3.0 n 4 315 4 a-c 4 1.329 a-h 4 2.o3 e- 1 4 0 co »
45-30 4 0.0 h 4 3.3 n 4 279 5 o-h 4 1.439 a-ß 4 1.44 g-? 4 0.30
45 * 45 4 3.0 h 4 3.0 h 4 230 - b-h 4 1,399 a-h 4 O.o9 .- «. 4 0.00 »
Square Fountain (Square (Square Square Square 1 Square
Variance df Average df Average df Average df Average df Average df Average
Error of 28 19.2 28 5.4 28 1145.8 23 J.013 28 26.2 '7 28 3.25
Treatment 87 21.6 37 5.4 3? 333.7 97 0.004 37 0. '7 97 0.10
An additional trial was conducted, as described above, except that only one cage was used per treatment and only the weight gain, mortality and injury scores were recorded. The data was not statistically evaluated. The results are shown in Table 25.
Table 25 Inoculated with E. acervulina and E. tenella at Mortality Injury Score Treatment Total Weight% Intestinal Mint! PPM F; n *; < gtns? Gain of Weight NC 0 370.2 231.0 3 0.00 0.00 IC 0 264.6 126.8 3 3.75 3.50 Example 14 25 240.1 96.1 50 8.33 3.67 50 320.3 179.5 50 9.00 3.67 100 263.4 125.7 25 0.00 1.33 Example 15 25 255.9 113.8 50 9.00 2.50 50 310.8 173.1 0 2.75 2.75 100 278.6 140.9 0 0.00 0.00 Example 16 25 275.3 137.4 50 9.33 3.67 50 338.3 196.7 25 0.33 2.33 100 324.0 181.9 0 0.00 1.00 Example 17 25 316.7 176.3 0 3.00 4.00 50 313.3 175.2 25 0.00 1.00 100 137.3 -2.8 75 0.00 3.00 Example 11 25 257.4 119.9 0 9.00 3.50 50 0.0 0.0 100 9.00 4.00 100 339.2 200.1 25 0.00 2.67 Example 12 25 215.4 76.7 25 9.00 3.67 50 136.2 -2.7 75 9.00 3.67 100 287.6 147.0 75 9.00 4.00 Example 13 25 168.9 28.4 75 7.50 4.00 50 260.3 118.5 25 7.25 3.25 100 234.2 95.0 25 9.00 3.67 Example 9 25 270.9 130.2 0 7.25 2.50 SO 315.7 176.7 0 3.00 2.00 100 270.0 129.6 0 3.00 0.00
An additional assay was conducted, as described above, except that only one cage was used per treatment; only injury scores were recorded; and the data was not statistically evaluated. The results are shown in Table 26. Mortality did not occur.
TABLE 26
Scores of Intestinal Lesions Ceca
Example 20 2 4 50 3 2 Ave # 1 1 3 Ave # 2 2 4 Ave # 3 Ave # 4
ino Ave # 1 3 4. Ave # 2 3 4 Ave # 3 3 4 Ave # 4 2 4
It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, the following is claimed as property:
Claims (10)
-
- A compound of formula characterized in that R1 represents perfluoroalkylsulfonyloxy of C? -C8 or 1,1,2,2-tetrafluoroethylsulfonyloxy, with the limitation that if R2 is not present, R1 is located in the 4-position; R3 represents perfluoroalkylsulfonyloxy of C? -C8 or 1,1,2,2-tetrafluoroethylsulfonyloxy, with the limitation that if R4 is not present, R3 is located at the 4 'position; each of R 2 and R 4 independently represent nitro, halo, cyano, thiocyanate, trifluoroacetylthio, C 1 -C 2 perfluoroalkyl, 1,1,2-tetrafluoroethyl, C 1 -C 2 perfluoroalkoxy, 1, 1,2, 2 tetrafluoroethoxy, C 1 -C 2 perfluoroalkylthio, 1,1,2,2-tetrafluoroethylthio, C 1 -C 2 perfluoroalkylsulfinyl, 1, 2, 2-tetrafluoroethylsulfinyl, C 1 -C 2 perfluoroalkylsulfonyl, or 1,1,2, 2-tetrafluoroethylsulfonyl; m represents 0 or 1; n represents 0, 1, or 2; and the sum of m and n is l, 2, or 3.
- A compound of formula characterized in that R1 represents perfluoroalkylsulfonyloxy of C? -C8 or 1, 1,2, 2-tetrafluoroethylsulfonyloxy, located in the 4-position or when an R2 is located in the 4 'position, in the 3-position; R3 represents perfluoroalkylsulfonyloxy of C 1 -C 8 6 1, 2, 2-tetrafluoroethylsulfonyloxy, located at the 4'-position or, when an R 4 is located at the 4'-position; and in the 3 'position; each of R2 and R4 independently represent nitro, halo, perfluoroalkyl of C? -C2, 1,1,2,2-tetrafluoroethyl, perfluoroalkoxy of C? -C2, 1,1,2,2-tetrafluoroethoxy, perfluoroalkylthio of C? -C 2, 1,1,2, 2-tetrafluoroethylthio, C 1 -C 2 perfluoroalkylsulfinyl, 1,1,2,2-tetrafluoroethylsulfinyl, C 1 -C 2 perfluoroalkylsulfonyl, or 1,1,2,2-tetrafluoroethylsulfonyl; m represents 0 or 1; n represents 0, 1, or 2; and the sum of m and n is 1 or 23. 3, 3'-bis (trifluoromethyl) -4,4'-bis- (trifluoromethylsulfonyloxy) carbanilide.
- 4. 3,3'-Dichloro-4,4'-bis (trifluoroethylsulfonyloxy) carbanilide.
- 5. The compound according to any of claims 1-4, characterized in that it is used in the prevention or treatment of coccidiosis in warm-blooded animals.
- 6. A premix of feed or animal fodder, characterized in that it comprises from 0.1 to 50.0 weight percent of an active agent, which is a compound according to any of claims 1-4.
- 7. A feed or animal feed, characterized in that it comprises 0.001 to 0.02 weight percent of an active agent, which is a compound according to any of claims 1-4.
- 8. The compound according to any of claims 1-4, characterized in that it is used in combination with a polyether antibiotic to prevent or treat coccidiosis in warm-blooded animals.
- 9. A premix of feed or animal fodder, useful for preventing or treating coccidiosis in a warm-blooded animal, characterized in that it comprises both a polyether antibiotic and a compound according to any of claims 1-4.
- 10. A feed or animal feed, characterized in that it comprises from 0.0001 to 0.01 weight percent of a polyether antibiotic and from 0.0001 to 0.01 weight percent of a compound according to any of claims 1-4.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US21274394A | 1994-03-14 | 1994-03-14 | |
US212,743 | 1994-03-14 | ||
US212743 | 1994-03-14 | ||
PCT/US1995/003333 WO1995024900A1 (en) | 1994-03-14 | 1995-03-14 | Carbanilide anticoccidials |
Publications (2)
Publication Number | Publication Date |
---|---|
MX9604044A MX9604044A (en) | 1997-09-30 |
MXPA96004044A true MXPA96004044A (en) | 1998-07-03 |
Family
ID=
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