CA1200200A - Anthelmintics - Google Patents
AnthelminticsInfo
- Publication number
- CA1200200A CA1200200A CA000419253A CA419253A CA1200200A CA 1200200 A CA1200200 A CA 1200200A CA 000419253 A CA000419253 A CA 000419253A CA 419253 A CA419253 A CA 419253A CA 1200200 A CA1200200 A CA 1200200A
- Authority
- CA
- Canada
- Prior art keywords
- active
- formula
- compounds
- group
- animals
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Abstract A composition for controlling helminths in both domestic animals and productive animals, which contains as active component a synergistic active-substance combi-nation. This active-substance combination comprises the individual compounds of the formula I
(I), wherein n is 0 or 1, and of the formula II
(II) wherein R1 is the group -NH-COOR-R3, in which R3 is an alkyl group having 1 to 9 carbon atoms, preferably methyl, or R1 is a thiazol-4-yl group, R2 is an alkyl group having 1 to 4 carbon atoms, preferably n-propyl, phenyl unsubstituted or substituted by halogen or alkyl, or it is a cycloalkyl group having 3 to 6 carbon atoms, and X is O, S, SO, CO, methylene, preferably S or SO, or an -NH-COO group, including the isomers embraced by the formula II, and also the acid addition salts of these compounds.
The synergistic compositions are used for controlling nematodes, cestodes and particularly trematodes in animals.
The active-substance combinations can be added to the feed or introduced into the drinking troughs, or can be admin-istered in preparations made up with customary carriers. in the solid or liquid form, to the animals perorally, by injectlon or by the pour-on method.
(I), wherein n is 0 or 1, and of the formula II
(II) wherein R1 is the group -NH-COOR-R3, in which R3 is an alkyl group having 1 to 9 carbon atoms, preferably methyl, or R1 is a thiazol-4-yl group, R2 is an alkyl group having 1 to 4 carbon atoms, preferably n-propyl, phenyl unsubstituted or substituted by halogen or alkyl, or it is a cycloalkyl group having 3 to 6 carbon atoms, and X is O, S, SO, CO, methylene, preferably S or SO, or an -NH-COO group, including the isomers embraced by the formula II, and also the acid addition salts of these compounds.
The synergistic compositions are used for controlling nematodes, cestodes and particularly trematodes in animals.
The active-substance combinations can be added to the feed or introduced into the drinking troughs, or can be admin-istered in preparations made up with customary carriers. in the solid or liquid form, to the animals perorally, by injectlon or by the pour-on method.
Description
1~.3~;~0~!
Case 5 13753/-ANTHELMINTICS
The present inventlon relates to novel anthelmintic compositions containing as active component an active-substance combination, and to the use o-f the compositions for controlling helminths, particularly trematodes, both in domestic animals and in productive animals.
The active-substance combinations on which the compositions according to the invention are based have a synergistic activity exceeding in an advantageous manner the additive effect of the individual active substances forming the combination. The active-substance combinations comprise the following individual active substances:
a compound of the formula I
C l~ N~
~ s - CH ( I ), Cl/ Cl I~
wherein n is O or l, and a compound of the formula II
Case 5 13753/-ANTHELMINTICS
The present inventlon relates to novel anthelmintic compositions containing as active component an active-substance combination, and to the use o-f the compositions for controlling helminths, particularly trematodes, both in domestic animals and in productive animals.
The active-substance combinations on which the compositions according to the invention are based have a synergistic activity exceeding in an advantageous manner the additive effect of the individual active substances forming the combination. The active-substance combinations comprise the following individual active substances:
a compound of the formula I
C l~ N~
~ s - CH ( I ), Cl/ Cl I~
wherein n is O or l, and a compound of the formula II
2 ~\ ~
Il \--R
.~ .\ ~ l (II) ' '~'' wherein Rl is the group -NH-COO-R3, in which R3 is an alkyl group having 1 to 9 carbon atoms, preferably methyl~ or R
is a thiazol-4-yl group, R2 is an alkyl group having 1 to 4 carbon atoms, preferably n-propyl, phenyl unsubstituted or substituted by halogen or alkyl, or it is a cycloalkyl group having 3 to 6 carbon atoms, and X is 0, S, SO, CO, methylene, preferably S or SO, or an -NH-COO group, including the isomers embraced by the formula II, and also tlle acid addition salts of these compounds.
The compounds described in the foregoing as active-sub~stance components of the compositions according to the invention are already known individually as being compounds having anthelmintic activity. Compounds of the formula I
are described for example in the German Offenlegungsschrift No. 2~815,621, and those of the formula II in Am. Journ.
Vet. Res. 37, 1515-16 (1976), in the Belgian Patent Spec-ification No. 793 358, and in Vet. Rec. 101, (9) 260-63, 1977.
The combination of different chemical compounds to produce a synergistic intensification of activity for controlling pests is gaining to an increasing extent in importance because of the possibility the combination offers for effectively counteracting the ever more frequent appearance of resistance of parasites to individual compounds. Consequently, the normally necessitated increase in the amounts of active substance used to overcome this build-up of resistance of the parasites can largely be avoided~ The resulting saving in the amounts of active substance applied has both economical and, by virtue of a lessening of environmental contamination, significant ecological advantages. In the administration of anthel-mintics to productive animals, this can mean a reduction in the dose applied, with which is simultaneously associated a lowering of the level of intoxication of the treated animals, with the result that their effective output during the treatment is not impaired.
Helminthic diseases among domestic animals and productive animals are widespread. These diseases lead to a reduc~ion in the growth and in the output of the afEected animals, and can even reswlt in their death. A
particularly dangerous helminthic disease is Fasciolose~
which is caused by parasitic liver flukes (for example lo Fasciola he2atica, Fasciola gigantica and Fascioloides spp.) and which occurs especially in ruminants, such as sheep and cattle. The losses attributable to this helminthic disease can assume considerable proportions, particularly when this disease occurs in epidernic form in herds of cattle. The control and prevention of Fasciolose are therefore looked upon as a serious problem urgentLy requiring a solution in order to avoid such9 above all economically grave, losses in animal production. In spite of the numerous known preparations in the field covering the control of helminths , it has hitherto not been possible to develop active substances which, in addition to having good general anthelminthic properties, exhibit a satis-factory action against adult and juvenile Fasciola genera in sheep and cattle while simultaneously having low toxicityO
It has now been found that the active-substance combinations which are contained in the compositions according to the invention, and which comprise a compound of the formula I and compounds of the formula II, display a high level of anthelmintic activity, having not only a wide spectrum of activity against nematodes, cestodes and trematodes, but also a very strongly marked action against Fasciola spp. in domestic animals and in productive animals o~
(ruminants and horses). To be emphasised as being particularly advantageous is the fact that the active-substance combinations on which the compositions according to the invention are based have, even in very small doses, a total action against liver flu~es in sheep, especially al.so against juveni.le stages, so that side-effects, wllich could result in an i.mpairment of the development and of the effective output of the treated animals during the period oE treatment, are avoidecl by virtue of small doses.
The action of the active-substance combinations against Fasclola hepatica is significantly above the adclitive action of the individual compounds forming the combinations.
The following combinations are to be regarded as being preferred:
~) 5-chloro-6-(2',3'-dichlorophenoxy)-2-methylthio-benzimidazole either with B) [5-(propylthio)-lH-benzimidazol-2-yl3-carbamic acid methyl ester ("~lbendazol")*, or with C) [5-(phenylthio)-lH-benzimidazol-2-yl.]-carbamic acid methyl ester ("Fenbendazol")*.
The applicable weight ratios of compounds of the formula I to compounds of the formula II for the active-substance combinations according to the present invention are within the range of l:So to 50:1. The combina-tion ratio of l:10 to 10:1 is particularly favoura.ble for bringing into effect the synergistic action.
Tests on sheep infested with Fasciola hepatica 36 sheep were artificially infested with metacercaria of Fasciola hepatica. For this purpose, the metacercaria were injected, in an aqueous 004% suspension of carboxy-methyl cellulose, directly into the rumen of the test *Trade Mark t. "
J~O~
animals. The animals were divided for medication into approximately equally large groups and into three control groups. After four weeks, the active substances were administered to the animals, in doses of 5 to 10 mg/kg of body weight, according to the specified combination.
The sheep were kept during the test in paddock boxes under normal conditions. In order to tes~ the action of the individual active-substance combinations, a count was made in the faeces, using a standard technique, 12 to 15 weeks after infestation and 8 to 11 weeks aEter medica~ion, of the eggs deposited by the ]iver flukes.Thetesta~m~s Nos,1-25,not belonging to group B and control group B'(=animals Nos.
26-36),were subsequently killed, and the number of liver flukes present was determined. The results were as follows:
Table 1 Sheep Substance EPG* ~ Adult flukes No. or mixture --(dose mg/kg) 14th 15th num- mean % re-week week ~ ber value duction l 65 125 12 3A (5.0) o 5 2 10.2 ~9.4 ~ 10 0 l~i o 0 0 6 5 o 4 7A + C (5.0 -~ 0 0 0 1.0 99.0 8 5.0) o o o 9 o o o lo o lo 2 12A + B (5.0 + o 15 0 0.8 99.2 13 ' o o 0 14 o o 0 ~o 300 78 16untreated 700 500 115 \ /
17control A' 510 620 11995.8 19 920 240 105 ,' O~
Iable 2 Sheep Substance EPG~i Adult flukes No. (dose mg/kg3 found by au opsy 12th 13th num- mean % re-week week ber value duction S~l 21 C (5.o - - 77 71 0 23 untreated 58 24 control C' ~ ~ 70 70 ><
82 ~/
26 360 lllO
27 B (4.6) 370 560 _ _ - **
32 untreated1290 1270 \ /
33 control Bl580 660
Il \--R
.~ .\ ~ l (II) ' '~'' wherein Rl is the group -NH-COO-R3, in which R3 is an alkyl group having 1 to 9 carbon atoms, preferably methyl~ or R
is a thiazol-4-yl group, R2 is an alkyl group having 1 to 4 carbon atoms, preferably n-propyl, phenyl unsubstituted or substituted by halogen or alkyl, or it is a cycloalkyl group having 3 to 6 carbon atoms, and X is 0, S, SO, CO, methylene, preferably S or SO, or an -NH-COO group, including the isomers embraced by the formula II, and also tlle acid addition salts of these compounds.
The compounds described in the foregoing as active-sub~stance components of the compositions according to the invention are already known individually as being compounds having anthelmintic activity. Compounds of the formula I
are described for example in the German Offenlegungsschrift No. 2~815,621, and those of the formula II in Am. Journ.
Vet. Res. 37, 1515-16 (1976), in the Belgian Patent Spec-ification No. 793 358, and in Vet. Rec. 101, (9) 260-63, 1977.
The combination of different chemical compounds to produce a synergistic intensification of activity for controlling pests is gaining to an increasing extent in importance because of the possibility the combination offers for effectively counteracting the ever more frequent appearance of resistance of parasites to individual compounds. Consequently, the normally necessitated increase in the amounts of active substance used to overcome this build-up of resistance of the parasites can largely be avoided~ The resulting saving in the amounts of active substance applied has both economical and, by virtue of a lessening of environmental contamination, significant ecological advantages. In the administration of anthel-mintics to productive animals, this can mean a reduction in the dose applied, with which is simultaneously associated a lowering of the level of intoxication of the treated animals, with the result that their effective output during the treatment is not impaired.
Helminthic diseases among domestic animals and productive animals are widespread. These diseases lead to a reduc~ion in the growth and in the output of the afEected animals, and can even reswlt in their death. A
particularly dangerous helminthic disease is Fasciolose~
which is caused by parasitic liver flukes (for example lo Fasciola he2atica, Fasciola gigantica and Fascioloides spp.) and which occurs especially in ruminants, such as sheep and cattle. The losses attributable to this helminthic disease can assume considerable proportions, particularly when this disease occurs in epidernic form in herds of cattle. The control and prevention of Fasciolose are therefore looked upon as a serious problem urgentLy requiring a solution in order to avoid such9 above all economically grave, losses in animal production. In spite of the numerous known preparations in the field covering the control of helminths , it has hitherto not been possible to develop active substances which, in addition to having good general anthelminthic properties, exhibit a satis-factory action against adult and juvenile Fasciola genera in sheep and cattle while simultaneously having low toxicityO
It has now been found that the active-substance combinations which are contained in the compositions according to the invention, and which comprise a compound of the formula I and compounds of the formula II, display a high level of anthelmintic activity, having not only a wide spectrum of activity against nematodes, cestodes and trematodes, but also a very strongly marked action against Fasciola spp. in domestic animals and in productive animals o~
(ruminants and horses). To be emphasised as being particularly advantageous is the fact that the active-substance combinations on which the compositions according to the invention are based have, even in very small doses, a total action against liver flu~es in sheep, especially al.so against juveni.le stages, so that side-effects, wllich could result in an i.mpairment of the development and of the effective output of the treated animals during the period oE treatment, are avoidecl by virtue of small doses.
The action of the active-substance combinations against Fasclola hepatica is significantly above the adclitive action of the individual compounds forming the combinations.
The following combinations are to be regarded as being preferred:
~) 5-chloro-6-(2',3'-dichlorophenoxy)-2-methylthio-benzimidazole either with B) [5-(propylthio)-lH-benzimidazol-2-yl3-carbamic acid methyl ester ("~lbendazol")*, or with C) [5-(phenylthio)-lH-benzimidazol-2-yl.]-carbamic acid methyl ester ("Fenbendazol")*.
The applicable weight ratios of compounds of the formula I to compounds of the formula II for the active-substance combinations according to the present invention are within the range of l:So to 50:1. The combina-tion ratio of l:10 to 10:1 is particularly favoura.ble for bringing into effect the synergistic action.
Tests on sheep infested with Fasciola hepatica 36 sheep were artificially infested with metacercaria of Fasciola hepatica. For this purpose, the metacercaria were injected, in an aqueous 004% suspension of carboxy-methyl cellulose, directly into the rumen of the test *Trade Mark t. "
J~O~
animals. The animals were divided for medication into approximately equally large groups and into three control groups. After four weeks, the active substances were administered to the animals, in doses of 5 to 10 mg/kg of body weight, according to the specified combination.
The sheep were kept during the test in paddock boxes under normal conditions. In order to tes~ the action of the individual active-substance combinations, a count was made in the faeces, using a standard technique, 12 to 15 weeks after infestation and 8 to 11 weeks aEter medica~ion, of the eggs deposited by the ]iver flukes.Thetesta~m~s Nos,1-25,not belonging to group B and control group B'(=animals Nos.
26-36),were subsequently killed, and the number of liver flukes present was determined. The results were as follows:
Table 1 Sheep Substance EPG* ~ Adult flukes No. or mixture --(dose mg/kg) 14th 15th num- mean % re-week week ~ ber value duction l 65 125 12 3A (5.0) o 5 2 10.2 ~9.4 ~ 10 0 l~i o 0 0 6 5 o 4 7A + C (5.0 -~ 0 0 0 1.0 99.0 8 5.0) o o o 9 o o o lo o lo 2 12A + B (5.0 + o 15 0 0.8 99.2 13 ' o o 0 14 o o 0 ~o 300 78 16untreated 700 500 115 \ /
17control A' 510 620 11995.8 19 920 240 105 ,' O~
Iable 2 Sheep Substance EPG~i Adult flukes No. (dose mg/kg3 found by au opsy 12th 13th num- mean % re-week week ber value duction S~l 21 C (5.o - - 77 71 0 23 untreated 58 24 control C' ~ ~ 70 70 ><
82 ~/
26 360 lllO
27 B (4.6) 370 560 _ _ - **
32 untreated1290 1270 \ /
33 control Bl580 660
3~ 860 850 / \
Key (Tables 1 + 2) substance A: 5-chloro-6-(2',3'-dichlorophenoxy)-2-methyl-thiobenzimidazole, substance C: [5-(phenylthio)-lH-benzimidazol-2-yl]-carbamic acid methyl ester ("Fenbendazol"), substance B: [5-(propYlthio)-lH-benzimidazol-2-yl]-carbamic acid methyl ester ("Albendazol").
FPG~ N~lmber ~ eggs o~liverfLukes per gram of faeces (week after carrying out of artificial infestation with metacercaria);
`~*: It is known from the literature that Albendazol in a comparab:Le dose is ineffective against 6-week-old and younger Liver flukes (Austral. Vet. J. 55, 431-432, 1979; Br:it. Vet. J. 138, 371-382~ 1982).
Results The active-substance combinations on which the compo-sitions according to the invention are based exhibited a degree of effec~iveness of over 99%, even against juvenile Fasciola hepatica. The action of these combinations is therefore significantly above the additive action of the individual compounds forming the combinations.
After administration of therapeutically effective doses of the active-substance combinations, clinical tests revealed no toxicity symptoms in the test animals.
The active-substance combinations according to the invention are used to control parasitic helminths in domestic and productive animals, such as cattle, sheep, goats~ horses, cats and dogs, and also in the red deer preserves. The combinations can be administered either in single doses to the animals, or in repeated doses, the single doses being, depending on the species of animal, preferably between 0.5 and 100 mg per kg of body weight.
A better effect can be obtained in some cases by a protracted administration, or smaller complete doses may suffice. The active substances or the mixtures containing them can also be added to the feed or be introduced into drinking troughs. The finished feed contains the active~
substance combinations preferably at a concentration of o.Oo5 to 0.1 per cent by weight. The compositions can be administered to the animals perorally in the form of solutions, emulsions, suspensions (drenches), powders, tablets, boluses or capsules. These preparations are prepared by the use for example of customary solid carriers~
such as kaolin, talcum, bentonite, sodium chloride, calcium phosphate or cottonseed meal, or by ~he use of liquids that do not react with the active substances, such as oils and other solvents and diluents harmless to the animal organism.
~ZJ~ 32~
Provided that the physical and toxicological properties of solutions or emulsions permit it, the active-substance combinations can be also injected into the animals subcutaneously, or can be applied by means of the pour-on-method. Furthermore, administration of the activesubstances to the animals is also possible by means of licking stones (salt) or molasses blocks.
When the anthelmintic compositions are in the form of feed concentrates, the main carriers used are feed materials, such as hay, production feed, fodder grain or protein concentrates. The feed can contain, in addition to the active substances, also additives, vitamins, anti-biotics, chemotherapeutical agents, or other pesticides, chiefly bacteriostatics, fungistatics, coccidiostatics, and also hormone preparations, substances having anabolic activity, or other substances promoting growth, affecting the quality of the meat of slaughter cattle, or being in some other way beneficial for the organism. They can also be combined with insecticides and acaricides, by virtue of which the action o~ the compositions is broadened and adapted to suit the given circumstances.
The anthelminthic compositions according to the invention are produced in a manner known per se by the intimate mixing and grinding of the active-substance combinations, comprising compounds of the Eormula I and compounds o~ the formula II, with suitable carriers, optionally with the addition of dispersing agents or solvents which are all inert to the active substances.
The anthelmintic compositions according to the invention can be used for example in the following preparations:
Solid preparations:
granulates (coated granules, impregnated granules and homogeneous granules); water dispersible concentrates of ~3~21~
active substance (wettable powders).
Liquid preparations:
solutions, pastes, emulsions or dispersions, such as ready-for-use suspensions (drenches).
The particle size of the carriers is advantageously up to about 0.1 mm for dusts and wettable powders, and 0.01 - 0.5 mm for granulates.
The concentration of the active-substance combinations in the solid preparations is 0.5 to 80%, and 0.5 to 50%
in the liquid preparations.
To these mixtures can also be added additives stabil-ising the active-substance combinations, and/or nonionic, anionic and cationic-active substances, which ensure for example better wettability (wetting agents) and dispers-lS ibility (dispersing agents).
Example: Water-dispersible powder mixture parts by weight o-f an active-substance combination of compounds of the formula I with compounds of the formula II are thoroughly mixed, in a mixer, with 0 7.5 parts by weight of an absorbent carrier, for example silicic acid, 59.4 parts by weight of a carrier, for example bolus alba or kaolin, 0.5 part by weight of oleic acid, 5.3 parts by weight of octylphenylpolyglycol ether, and 2.3 parts by weight of a stearyl-benzimidazole derivative.
This mixture is ground in a dowelled disk mill or an air-jet mill until the particle size is 5-15~um. The wettable powder thus obtained gives a good suspension in water.
Key (Tables 1 + 2) substance A: 5-chloro-6-(2',3'-dichlorophenoxy)-2-methyl-thiobenzimidazole, substance C: [5-(phenylthio)-lH-benzimidazol-2-yl]-carbamic acid methyl ester ("Fenbendazol"), substance B: [5-(propYlthio)-lH-benzimidazol-2-yl]-carbamic acid methyl ester ("Albendazol").
FPG~ N~lmber ~ eggs o~liverfLukes per gram of faeces (week after carrying out of artificial infestation with metacercaria);
`~*: It is known from the literature that Albendazol in a comparab:Le dose is ineffective against 6-week-old and younger Liver flukes (Austral. Vet. J. 55, 431-432, 1979; Br:it. Vet. J. 138, 371-382~ 1982).
Results The active-substance combinations on which the compo-sitions according to the invention are based exhibited a degree of effec~iveness of over 99%, even against juvenile Fasciola hepatica. The action of these combinations is therefore significantly above the additive action of the individual compounds forming the combinations.
After administration of therapeutically effective doses of the active-substance combinations, clinical tests revealed no toxicity symptoms in the test animals.
The active-substance combinations according to the invention are used to control parasitic helminths in domestic and productive animals, such as cattle, sheep, goats~ horses, cats and dogs, and also in the red deer preserves. The combinations can be administered either in single doses to the animals, or in repeated doses, the single doses being, depending on the species of animal, preferably between 0.5 and 100 mg per kg of body weight.
A better effect can be obtained in some cases by a protracted administration, or smaller complete doses may suffice. The active substances or the mixtures containing them can also be added to the feed or be introduced into drinking troughs. The finished feed contains the active~
substance combinations preferably at a concentration of o.Oo5 to 0.1 per cent by weight. The compositions can be administered to the animals perorally in the form of solutions, emulsions, suspensions (drenches), powders, tablets, boluses or capsules. These preparations are prepared by the use for example of customary solid carriers~
such as kaolin, talcum, bentonite, sodium chloride, calcium phosphate or cottonseed meal, or by ~he use of liquids that do not react with the active substances, such as oils and other solvents and diluents harmless to the animal organism.
~ZJ~ 32~
Provided that the physical and toxicological properties of solutions or emulsions permit it, the active-substance combinations can be also injected into the animals subcutaneously, or can be applied by means of the pour-on-method. Furthermore, administration of the activesubstances to the animals is also possible by means of licking stones (salt) or molasses blocks.
When the anthelmintic compositions are in the form of feed concentrates, the main carriers used are feed materials, such as hay, production feed, fodder grain or protein concentrates. The feed can contain, in addition to the active substances, also additives, vitamins, anti-biotics, chemotherapeutical agents, or other pesticides, chiefly bacteriostatics, fungistatics, coccidiostatics, and also hormone preparations, substances having anabolic activity, or other substances promoting growth, affecting the quality of the meat of slaughter cattle, or being in some other way beneficial for the organism. They can also be combined with insecticides and acaricides, by virtue of which the action o~ the compositions is broadened and adapted to suit the given circumstances.
The anthelminthic compositions according to the invention are produced in a manner known per se by the intimate mixing and grinding of the active-substance combinations, comprising compounds of the Eormula I and compounds o~ the formula II, with suitable carriers, optionally with the addition of dispersing agents or solvents which are all inert to the active substances.
The anthelmintic compositions according to the invention can be used for example in the following preparations:
Solid preparations:
granulates (coated granules, impregnated granules and homogeneous granules); water dispersible concentrates of ~3~21~
active substance (wettable powders).
Liquid preparations:
solutions, pastes, emulsions or dispersions, such as ready-for-use suspensions (drenches).
The particle size of the carriers is advantageously up to about 0.1 mm for dusts and wettable powders, and 0.01 - 0.5 mm for granulates.
The concentration of the active-substance combinations in the solid preparations is 0.5 to 80%, and 0.5 to 50%
in the liquid preparations.
To these mixtures can also be added additives stabil-ising the active-substance combinations, and/or nonionic, anionic and cationic-active substances, which ensure for example better wettability (wetting agents) and dispers-lS ibility (dispersing agents).
Example: Water-dispersible powder mixture parts by weight o-f an active-substance combination of compounds of the formula I with compounds of the formula II are thoroughly mixed, in a mixer, with 0 7.5 parts by weight of an absorbent carrier, for example silicic acid, 59.4 parts by weight of a carrier, for example bolus alba or kaolin, 0.5 part by weight of oleic acid, 5.3 parts by weight of octylphenylpolyglycol ether, and 2.3 parts by weight of a stearyl-benzimidazole derivative.
This mixture is ground in a dowelled disk mill or an air-jet mill until the particle size is 5-15~um. The wettable powder thus obtained gives a good suspension in water.
Claims (5)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A synergistic composition for controlling parasitic helminths, which composition contains as active component an effective amount of an active substance combination in synergistic proportions comprising at least one compound of the formula I
(I) wherein n is 0 or 1, and at least one compound of the formula II
(II) wherein R1 is the group -NH-COO-R3, in which R3 is an alkyl group having 1 to 9 carbon atoms, or R1 is a thiazol-4-yl aroup, R2 is an alkyl group having 1 to 4 carbon atoms, phenyl unsubstituted or substituted by halogen or alkyl, or it is a cycloalkyl group having 3 to 6 carbon atoms, and X is O, S, SO, CO, methylene, or an -NH-COO group, including the isomers embraced by the formula II, and also the acid addition salts of these compounds, together with suitable carriers and/or distributing agents and diluents.
(I) wherein n is 0 or 1, and at least one compound of the formula II
(II) wherein R1 is the group -NH-COO-R3, in which R3 is an alkyl group having 1 to 9 carbon atoms, or R1 is a thiazol-4-yl aroup, R2 is an alkyl group having 1 to 4 carbon atoms, phenyl unsubstituted or substituted by halogen or alkyl, or it is a cycloalkyl group having 3 to 6 carbon atoms, and X is O, S, SO, CO, methylene, or an -NH-COO group, including the isomers embraced by the formula II, and also the acid addition salts of these compounds, together with suitable carriers and/or distributing agents and diluents.
2. A composition for controlling parasitic helminths, according to Claim 1, which contains as active component an active-substance combination comprising:
5-chloro-6-(2',3'-dichlorophenoxy)-2-methylthiobenzimidazole and [5-(propylthio)-1H-benzimidazol-2-yl]-carbamic acid methyl ester, together with suitable carriers and/or distributing agents and diluents.
5-chloro-6-(2',3'-dichlorophenoxy)-2-methylthiobenzimidazole and [5-(propylthio)-1H-benzimidazol-2-yl]-carbamic acid methyl ester, together with suitable carriers and/or distributing agents and diluents.
3. A composition for combating parasitic helminths, according to Claim 1, which contains as active component an active-substance combination comprising:
5-chloro-6-(2',3'-dichlorophenoxy)-2-methylthiobenzimidazole and [5-(phenylthio)-1H-benzimidazol-2-yl]-carbamic acid methyl ester, together with suitable carriers and/or distributing agents and diluents.
5-chloro-6-(2',3'-dichlorophenoxy)-2-methylthiobenzimidazole and [5-(phenylthio)-1H-benzimidazol-2-yl]-carbamic acid methyl ester, together with suitable carriers and/or distributing agents and diluents.
4. An anthelmintic composition according to anyone of Claims 1 to 3, wherein the weight ratio, in the active-substance combination, of compounds of the formula I to compounds of the formula II is 1:50 to 50:1.
5. An anthelmintic composition according to Claims 1 to 3, wherein the weight ratio, in the active-substance combination, of compounds of the formula I to compounds of the formula II is 1:10 to 10:1.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH17982 | 1982-01-13 | ||
| CH179/82-7 | 1982-01-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1200200A true CA1200200A (en) | 1986-02-04 |
Family
ID=4181065
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000419253A Expired CA1200200A (en) | 1982-01-13 | 1983-01-11 | Anthelmintics |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0084516B1 (en) |
| JP (1) | JPS5936613A (en) |
| AU (1) | AU1031183A (en) |
| BG (1) | BG38936A3 (en) |
| CA (1) | CA1200200A (en) |
| DE (1) | DE3361358D1 (en) |
| DK (1) | DK10583A (en) |
| ES (1) | ES8503199A1 (en) |
| GB (1) | GB2113091B (en) |
| IL (1) | IL67659A (en) |
| MA (1) | MA19678A1 (en) |
| PH (1) | PH19183A (en) |
| ZA (1) | ZA83186B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| YU2792A (en) * | 1991-01-19 | 1995-01-31 | Hoechst A Ktiengesellschaft | DISPERSIONS OF FINE PARTICLES, ANTIHELMINTENTALLY EFFECTIVE DERIVATIVES, BENZIMIDAZOLE OR BENZTIAZOLE OR PRO-BENZIMIDAZOLE IN WATER |
| AU687062B2 (en) * | 1993-05-26 | 1998-02-19 | Commonwealth Scientific And Industrial Research Organisation | Controlled release antiparasitic compositions |
| ES2170099T3 (en) * | 1993-05-26 | 2002-08-01 | Commw Scient Ind Res Org | ANTIPARASITARY COMPOSITIONS. |
| AU679753B2 (en) * | 1993-06-15 | 1997-07-10 | Australian National University, The | Synergistic anthelmintic compositions |
| ZA944191B (en) * | 1993-06-15 | 1995-02-08 | Univ Australian | Synergistic anthelmintic compositions |
| AUPQ770200A0 (en) * | 2000-05-23 | 2000-06-15 | Commonwealth Scientific And Industrial Research Organisation | Tablets for animals |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH634306A5 (en) * | 1977-04-12 | 1983-01-31 | Ciba Geigy Ag | BENZIMIDAZOLE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND ANTHELMINTIC AGENTS CONTAINING THESE COMPOUNDS AS ACTIVE INGREDIENTS. |
| JPS57139012A (en) * | 1981-02-23 | 1982-08-27 | Sankyo Co Ltd | Anthelmintic composition |
-
1983
- 1983-01-03 MA MA19895A patent/MA19678A1/en unknown
- 1983-01-07 DE DE8383810006T patent/DE3361358D1/en not_active Expired
- 1983-01-07 EP EP83810006A patent/EP0084516B1/en not_active Expired
- 1983-01-10 PH PH28368A patent/PH19183A/en unknown
- 1983-01-11 GB GB08300647A patent/GB2113091B/en not_active Expired
- 1983-01-11 CA CA000419253A patent/CA1200200A/en not_active Expired
- 1983-01-11 IL IL67659A patent/IL67659A/en unknown
- 1983-01-12 BG BG8359320A patent/BG38936A3/en unknown
- 1983-01-12 ZA ZA83186A patent/ZA83186B/en unknown
- 1983-01-12 DK DK10583A patent/DK10583A/en not_active Application Discontinuation
- 1983-01-12 AU AU10311/83A patent/AU1031183A/en not_active Abandoned
- 1983-01-12 ES ES518931A patent/ES8503199A1/en not_active Expired
- 1983-01-13 JP JP58002934A patent/JPS5936613A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| MA19678A1 (en) | 1983-10-01 |
| EP0084516A1 (en) | 1983-07-27 |
| IL67659A (en) | 1985-07-31 |
| GB8300647D0 (en) | 1983-02-09 |
| JPS5936613A (en) | 1984-02-28 |
| AU1031183A (en) | 1983-07-21 |
| PH19183A (en) | 1986-01-23 |
| DE3361358D1 (en) | 1986-01-16 |
| ZA83186B (en) | 1983-10-26 |
| DK10583A (en) | 1983-07-14 |
| GB2113091A (en) | 1983-08-03 |
| EP0084516B1 (en) | 1985-12-04 |
| DK10583D0 (en) | 1983-01-12 |
| ES518931A0 (en) | 1985-02-16 |
| ES8503199A1 (en) | 1985-02-16 |
| GB2113091B (en) | 1985-07-31 |
| BG38936A3 (en) | 1986-03-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1061213C (en) | Combating fish parasites | |
| JP4495256B2 (en) | Composition for systemic control of parasites of isothermal animals | |
| CA1200200A (en) | Anthelmintics | |
| US3065133A (en) | Imidazoles for the control of histomoniasis | |
| NZ205238A (en) | Synergistic mixtures as anthelmintic | |
| US5416102A (en) | Method of preventing the reinfestation of dogs and cats by fleas | |
| EP2393366B1 (en) | Herbal compositions for the control of hematophagous parasites | |
| EP0125004B1 (en) | Synergistic antiparasitic compositions | |
| US4436737A (en) | Anthelmintic compositions | |
| JPH07188009A (en) | Anti-coccidium composition | |
| CA1217430A (en) | Anthelmintics | |
| US3987181A (en) | Certain 2-trifluoromethylbenzimidazoles as anthelmintics | |
| IE832793L (en) | Synergistic anthelmintic composition. | |
| US4034110A (en) | Anthelmintics effective against liver flukes | |
| US4659713A (en) | Quinoxalinedione compounds useful for controlling coccidiosis | |
| Larson et al. | Acute and subchronic toxicity of mirex in the rat, dog, and rabbit | |
| US4070476A (en) | Topical anthelmintic compositions and methods of use | |
| US3968209A (en) | Anthelmintic use of phosphorylated thioureas | |
| JPH07173055A (en) | Anticoccidium composition | |
| US2797182A (en) | Cadmium anthranilate containing anthelmintics | |
| US3382148A (en) | Composition and methods for controlling coccidiosis in poultry | |
| US4042703A (en) | Method of treating and preventing coccidiosis | |
| CA1123455A (en) | 2,4-dichloro-n-(chloro-(2,4- dichloropheyl)methylene)benzenecarbohydrazonyl chloride, method of making and method of controlling manure breeding insects | |
| Bosman | A comparison of sheep worm dosing routines, as adjudged by wool production, and bodyweight changes | |
| CA2444841A1 (en) | Increasing phosphorus uptake from the gut of dairy cows by supplementing with 1-alpha-hydroxylated vitamin d |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |