IE69667B1 - Formulations comprising praziquantel and another anthelmintic - Google Patents

Formulations comprising praziquantel and another anthelmintic

Info

Publication number
IE69667B1
IE69667B1 IE920446A IE920446A IE69667B1 IE 69667 B1 IE69667 B1 IE 69667B1 IE 920446 A IE920446 A IE 920446A IE 920446 A IE920446 A IE 920446A IE 69667 B1 IE69667 B1 IE 69667B1
Authority
IE
Ireland
Prior art keywords
praziquantel
anthelmintic
composition
levamisole
formulation
Prior art date
Application number
IE920446A
Other versions
IE920446A1 (en
Inventor
Colin Manson Harvey
Original Assignee
Ancare Distributors
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=19923486&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IE69667(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Ancare Distributors filed Critical Ancare Distributors
Publication of IE920446A1 publication Critical patent/IE920446A1/en
Publication of IE69667B1 publication Critical patent/IE69667B1/en

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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Anthelmintic compositions containing praziquantel (a pyrazinoisoquinoline derivative; (2(Cyclohexylcarbonyl))- 1,2,3,6,7,-11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one) together with at least one other anthelmintic. Formulations are described containing; (i) praziquantel and levamisole, (ii) praziquantel and albendazole, (iii) praziquantel and oxfendazole, (iv) praziquantel and moxidectin, (v) praziquantel and ivermectin. The avermectin component may be replaced by Milbemycin D, or other milbemycins.

Description

This invention relates to pharmaceutical compositions for the treatment of helminthiasis in warm-blooded animals, more particularly cattle, sheep, goats, and other domesticated herbivores.
BACKGROUND * Helminthiasis is a widely occurring disease in farmed animals. It commonly causes clinical disease and has significant adverse economic effects on farming economies when present at subclinical levels. Over the past twenty-five years a number of initially successful anthelmintic agents, with relatively specific effects on the metabolism of smaller or larger groups of endoparasites have been discovered, trialled, and used successfully to control helminthiasis on farms. Various groups of compounds have a greater or lesser spectrum of activity - that is to say they are able to destroy a wider or smaller range of parasite. For example, the widely used ivermectin is active against parasitic roundworms and also against some ectoparasites, yet it is inactive against tapeworms because of a difference in their biochemical constitution. Triclabendazole” is active only against the liver fluke Fasciola hepatica.
Unfortunately, resistance to the effects of particular compounds or related families has usually developed with time, after repeated use of the same compound, and has become one of the major problems in the use of these anthelmintic agents. In fact, the growth of drench resistance seems to be overtaking the ability of scientists to develop new drenches. The spread of sheep measles (cysts of the taenia ovis species of tapewoim) is one such problem.
There is a need, therefore, for alternative anthelmintic formulations having the breadth of activity of the benzimidazole drugs (for example) but which slows the advancement of drench resistance.
OBJECT It is an object of this invention to provide novel pharmaceutical compositions having anthelmintic activity.
X According to the invention there is provided an anthelmintic composition including an effective amount of the anthelmintic praziquantel together , with effective amounts of at least one other anthelmintic, wherein the other anthelmintic is selected from the group comprising the avermectins; * milbemycins; levamisole; tetramisole; or a substituted benzimidazole carbamate, with the proviso that it does not include febantel, pyrantel, oxamniquine nor furapromidium.
Praziquantel (2(Cyclohexylcarbonyl))-12,3,6,7 ,-11 b-hexahydro~4H-pyrazino[2,l* a]isoquinolin-4-one) has for many years been used to control cestode infestations and schistosomiasis in humans. The surprising discovery that the efficacy of praziquantel can j Q be enhanced in domesticated animals by simultaneous administration with other anthelmintics has been exploited in the present invention, which offers improved efficacy in the control of cestodes, together with simultaneous control of nematode infestations.
Examples of suitable benzimidazole drugs include drugs such as mebendazole, fenbenIg dazole, oxfendazole, albendazole, cambendazole, parbendazole, oxibendazole, flubendazole and cyclobendazole.
Preferably, in the case of compositions incorporating levamisole, the composition has a pH less than 4.0 and in the most preferred aspect the pH is about 3.0.
Optionally, the composition may contain other veterinary products (including other anthelmintics).
The anthelmintic compositions of the invention may be used for treating 25 helminthiasis in animals.
When administered to sheep we prefer to administer the composition as a drench having an effective amount of praziquantel in the range of 4 to 4 mg/kg of body weight Since praziquantel is a relatively insoluble material, we have devised formulations for administration in the form of drenches and examples are included in this specification.
♦· We have previously found that combining benzimidazole drenches with levamisole drenches results in an unstable product due to die different pH values needed to maintain the stability of the individual products. Mixtures of levamisole as tbe hydrochloride together with praziquantel are stable, provided that the pH of the mixture is lower than approximately 4.
These and other aspects of the invention, which will be considered in all its novel aspects, will be apparent from the following description, which is given by way of example only.
GENERAL FORMULATION A typical formula for this invention would include the following active ingredients: praziquantel AND benzimidazole OR levamisole OR ivermectin OR moxidectin OR doramectin active in a range of activity from 05 - 15% w/v active in a range of activity from 1 - 15% w/v active in a range of activity from 1 - 10% w/v active in a range of activity from 0.05 - 1% w/v active in a range of activity from 0.05 - 1% w/v active in a range of activity from 0.05 - 1% w/v and one or more of the following ingredients to enhance stability and characteristics of the composition: viscosity agents surfactants sanitizers acidifiers stabilizers EXAMPLE I: PranquantelZLevamisoIe HQ Drench ·'? pH of 3.4 Viscosity @ 20 *C Density at 20 ’C = 1.025 kg/1 = 20 sec. (Ford no. 4 cup) ingredient gm! 100ml Water (hot) 2.0 Polyoxystearate 40USP/NF 2.50 PEG 6000* 3.00 praziquantel 1.88 Defoamer RD 0.20 Water (cold) to 100 ml Potassium sorbate BP 0.18 Citric Acid (anhyd) BP 0.30 Levamisole HCl BP 3.75 Xanthan Gum USP/NF 0J0 Mono propylene glycol BP 0.40 Colloidal anhydrous silica BP 1.00 Foimalehyde solution BP 0.20 100.00 *PEG 6000 is an abbreviation for Polyethylene Glycol 6000 USP/NF.
We have found that it is possible to make an acidified praziquantel drench in which the stability of levamisole can be maintained without affecting die praziquantel component. The acidity of the resulting product is preferably of a pH of less than 4.0, preferably around 3.0. A lower pH do wn to 2.0 is preferable if minerals are added to the drench. We have found that the pH of the above examples will vary slightly on a batch by batch basis.
Manufacturing Instructions for Composition of Example 1 1. Praziquantel premix - measure the hot water into a premix vessel, add the PEG 6000 and polyoxystearate 40 and mix until fully melted (approximately 65’C). Use external heating if required. Add the praziquantel and Defoamer RD and silverson until smooth and lump free. 2. Measure the bulk of die cold water into the production tank, add the potassium sorbate, citric acid, and levamisole hydrochloride and stir to dissolve. 3. Add the hot praziquantel premix to the production tank and stir until fully dispersed and lump-free. 4. Premix the Monopropylene glycol and Xanthan Gum, add to the batch and silverson until dispersed and until the viscosity has fully developed.
. Add tiie colloidal anhydrous silica and silverson until fully dispersed. 6. When the batch temperature is below 40*C add the formalin and stir to dissolve. 7. Add the remaining water to make up to volume. 8. Take a test sample for laboratory analysis.
The procedure called silversoning” is essentially mixing or dispersing in a device providing high shear rates within the fluid.
EXAMPLE 2: Prazjquanrr.l/Alhf.nHayoIe Drench By way of a second embodiment, a combination with an albendazole would be prepared using the following constituents: Water (hot) gmllOOrrd 2.00 PEG 6000 2.50 Polyoxystearate 40 3.00 Albendazole 238 Defoamer RD 030 Praziquantel 230 Water (cold) to 100ml Potassium soibate 0.18 Citric acid 030 Xanthan Gum USP/NF 030 Monopropylene glycol 0.40 Formalin 030 Colloidal anhydrous silica 1.00 100 ml The pH of such a suspension is expected to be in the range of from 3.5 to 5.5.
Combinations with other benzimidazole-type compounds can be formulated in a manner similar to that of Example 2.
EXAMPLE 3: Praziquantel/Iveimectin Drench Combinations with avermectin-related compounds can be made as non-aqueous or aqueous suspensions depending on the stability of the avexmectin compound. For example, a formulation including ivermectin and praziquantel could be: gmllOOml Ivermectin 0.1 Praziquantel 1.88.
Propylene glycol 40.00 Water to 100ml The suspension would have a neutral pH.
Other avennectins such as doramectin ormoxidectin may be used in place of ivermectin.
It is also possible to prepare a solution of praziquantel with appropriate organic solvents.
The resulting product is not only stable but also allows the farmer to obtain control of a wider range of parasites.
EXAMPLE 4: Praaquantel/Oxfendaznle A combination with an albendazole would be prepared using the following constituents: Water (hot) gml100ml 2.00 PEG 6000 2J0 Polyoxystearate 40 3.00 Oxfendazole 2265 Defoamer RD 020 Praziquantel 250 Water (cold) to 100ml Potassium sorbate 0.18 Citric acid 0.30 Xanthan Gum USP/NF 0.20 Monopropylene glycol 0.40 Foimalin 020 Colloidal anhydrous silica 1.00 100 ml EXAMPLES: Prariquantel/Moxidcctin gmllOOnd Praziquantel 2.0 Moxidectin 0.10 Propylene glycol 20.0 Xanthan Gum USP/NF 0.2 Water to 100 ml 100ml EXAMPLES: Praziquantel/Ivcrmectin gm! 100ml Praziquantel XO Ivennectin 0.08 Ethanol 20.0 Propylene glycol to 100ml 100 ml In addition, it is possible to include in the composition other veterinary products including ectoparasiticides, as well as other endoparasiticides, minerals, and trace elements as required. In the following trials reference will be made to the praziquantel/Levamisole formulation of Example 1. In some of the trials the formulation of Example 1 may include minerals and trace elements.
The compositions may be administered to mammals preferably by mouth as a drench, and as a single dose.
TRIALS The formulation of Example 1 has been shown in a series of New Zealand trials to be highly effective in controlling benzimidazole resistant roundworms and tapeworms in sheep.
While levamisole has been well researched for the control of helminths in sheep, there historically has been little information on praziquantel in the ovine. Thomas & Gonnert [Research in Veterinary Science (1978) 24,20] report a high efficacy in the control of Moniezia spp at a dose of 2.5mg/kg, while other studies against liver tapeworm (Stilesia 2q hepatica) demonstrated efficacy at 15mg/kg.
A recent study by C. Bauer [Veterinary Record (1990) 127, 353-354] demonstrated an adequate efficacy against Moniezia expensa in lambs at a dose of 3.75mg/kg. Based on this study a praziquantel dose of 3.75mgZkg was chosen.
TRIAL I Summary Two groups of milk lambs - slaughter at ten days. The formulation of Example 1 at a dose of 2mI/10kg of body weight. epg Reduction % Formulation of Example 1 Control Strong 98% (800%) Nem. % Reduction worm Haemonchus spp 100% counts versus controls Osteztagia spp 97% Nematodirus spp 100% Tiichostrongylus spp 100% Cooperia 100% Moniezia Scoleces 100% Segments 98% A high level of efficacy was demonstrated by the formulation of Example 1 against roundworms and tapeworms.
TRIAL REPORT I OBJECTIVE To assess by dosing and slaughter trial the efficacy and dose compatibility of the formulation of Example 1 mt lambs in die control of tapeworm and roundworm.
MATERIALS The formulation of Example 1 TRIAL DESIGN Two groups of lambs were divided into two random groups as follows: Group 1 Ο Dosed with the formulation of Example 1 Dose rate 2 ml/lOkg bodyweight Lambe Nos. 43,42,55,23,14,61,45,47 All lambs were tagged, weighed and faecal sampled predosing.
All lambs were slaughtered at 10 days post treatment and tapeworm and nematode worm counts done on the abomasum and small intestine.
Reaction of animals at drenching observed and no effects noticed EGGSGRAM W DAY CRITICAL SLAUGHTER WORM COUNTS Tag No. Wgt Dose Stmng. Nem. Stang. Nem. Haem. Ostert. Trich. Nema. Trich. Coop. MONEZ1A kgs ml Seolex Segments mL GROUP 1 - UEWTAPEAmWOkg 43 22 83 250 42 24 9.6 SO SS 20 8Ό 350 23 15 6.0 650 14 16 6.4 2200 61 17 63 300 45 22 8.8 250 47 19 73 200 500 200 400 SO MEAN 531.2 — 62 1373 — — · • 03 GROUP?-CONTROL 37 20 1650 - 3750 - 150 14000 - 200 2200 400 8 3 20 16 1000 - 2800 - 250 1400 - - 1000 200 8 100 5 -26 900 - 1400 - 40 6000 - - 2600 400 3 1 11 19 600 - 950 - 180 800 - - 600 200 - - 17 20 600 - 2650 - 70 3000 - 100 700 500 2 8 63 17 400 - 2400 - 140 5800 - 100 2000 800 2 45 51 18 100 - 960 - 10 1600 - 100 600 100 2 60 32 18 200 - 450 — 30 2400 — — 500 200 2 35 MEAN 6812 - 6168.7 - 878 4375 - 623 1275 350 33 313 The tabulated results above show for each result the weights of the lambs, the dose administered, the faecal egg counts piedosing and the 10 day worm counts. The efficacy e of the formulation of Example 1 on Moniezia expansa is demonstrated. The levamisole shows no diminution in its efficacy on the common nematodes in lambs. t TRIAL Π &2Q2Q2SX Three groups of lambs - slaughter at ten days.
Group 1 Formulation of Example 1 - lml/5kg Group 2 Albendazole - lml/5kg Group 3 Control - untreated % epg Reduction Formulation of Example 1 Albendazole Control Strong 15% 45% (788%) Nem 100% + + % Reduction Haemonchus spp 60% 30% worm counts Ostertagia spp 82% 96% versus Nematodirus spp 85% (23%) controls Trichostrongylus spp 100% 25% Coopcriaspp Moniezia • — Scoleces 99% 19% Segments 100% 23% Clear evidence of resistant nematodes to levamisole and albendazole. Albendazole resistant moniezia were cleared by the formulation of Example 1.
TRIAL REPORT Π OBJECTIVE To assess by dosing and slaughter trial the efficacy and dose compatibility of the formulation of Example 1 on lambs in the control of tapeworm and roundworm.
MATERIALS 1. Formulation of Example 1 8mg/kg levamisole/3.75 mg/kg praziquantal 2. Albendazole TRIAL DESIGN Three groups of lambs were divided into three random groups as follows: Group 1 - 8 Lambs, Group 2-8 Lambs, Group 3- 7 Lambs.
Group 1 Dosed with the formulation of Example 1 (3.75 mg/kg praziquantal) (8mg/kg levamisole) Dose rate 1 ml/1 kg bodyweight Lamb Nos. 50,54,37,75,35,35,30,61,52 Group 2 Albendazole lml/5kg 25 Lamb Nos. 48,64,56,33,60,58,44,59 Group 3 Control Lamb Nos. 40,32,57,49,43,46,51 All lambs were tagged, weighed and faecal sampled predosing.
All lambs were slaughtered at 10 days post treatment and tapeworm and nematode worm counts done on the abomasum and small intestine.
Reaction of animals at drenching observed and no effects noticed.
EGGSX3RAM 10 DAY CRITICAL SLAUGHTER WORM COUNTS Tag No. Wgt Dose Strong. Nam. Strong. Nam. Haem. Ostert. Trich. Nama. Trich. Coop. MONEZIA kgs ml Scolax Segments $ mL GROUP 1-UEVITAPE II (Imiekg) 50 16 36 1900 100 - - - 100 - 100 - 54 14 36 50 - - - - - 30 - 37 14 36 450 75 13 36 600 - - - 10 - - - 35 14 36 350 50 750 - - 200 - 100 - - 1 30 14 36 900- - 2850 - 100 1900 - - - _ _ 61 .12 25 300 - - 20 - - - _ _ 52 26 56 300 - Missing LEAN 6065 196 514 - 145 3195 - 326 - - 0.14 GROUP 2-ALBENDAZOLE flmlStart 48 16 - 750 - so - 30 100 - 100 - - 55 - 64 14 - - - 500 - X 100 - 20 - - 4 - 56 14 - 450 - ISO - - - - 700 - - 11 40 33 13 - 150 - 400 - 20 - - 1000 100 - 34 10 60 14 - 2250 - 1000 200 40 100 - 100 - - 39 27 56 14 - 900 - 700 50 20 - 100 100 - - 16 14· 44 12 - 700 - 150 50 100 200 - 100 - - 29 3 59 26 950 - 400 — - - - 10 - 4 - MEAN 768.7 — 4168 375 306 62.5 125 2665 1125 24.0 11.1 GROUP 3-CONTROL 40 450 - 1350 - 40 1200 - 300 100 - 24 15 32 850 - 7300 500 60 2500 - 400 200 - 3 - 57 500 950 50 30 1000 - 300 - - 18 1 49 - - 1750 150 20 400 - - - - 52 45 43 750 - 1060 - X 3200 - 200 IX - 49 X 46 450 - 13450 - 40 2200 - 100 500 - 32 2 400DEAD-;MEAN 485.7 43060 116.0 3681750 - . 2166 1SOO - 206 155 The tabulated results above show for each.result the weights of the lambs, the dose administered, the faecal egg counts predosing and post dosing and the 10 day worm counts. The efficacy of the formulation of Example 1 on Moniezia expansa is demonstrated. The levamisole and albendazole group results shows efficacy on the common nematodes in lambs is not as high as desired as resistance appears to be present to both these actives.
The albendazole was not effective in its efficacy against Monezia expansa. The formulation of Example 1 shows a very successful level of elimination of this tapeworm when in combination with levamisole.
TRIAL REPORT ΠΙ LOCATION OBJECTIVE To assess by dosing and slaughter trial the efficacy and dose compatibility of the formulation of Example 1 on lambs in the control of tapeworm and roundworm.
MATERIALS 1. The formulation of Example 1 including minerals, and trace elements such as copper, cobalt, selenium, iodine and zinc. 8mg/kg levamisole/3.75 mg/kg praziquantal with Minerals 2. Albendazole (Valbazen) TRIAL DESIGN Three groups of lambs were divided into three random groups as follows: Group 1-8 Lambs, Group 2-8 Lambs, Group 3-8 Lambs » Group 1 Dosed with the formulation of Example 1 including minerals and trace elements such as copper, cobalt, selenium, iodine and zinc. (3.75 mg/kg praziquantal) (8mg/kg levamisole) Dose rate 1 ml/5 kg bodyweight Lamb Nos. 17,20,23,33,36,37,102,108 v Group 2 Albendazole lml/5kg m Lamb Nos. 12,21,26,39,43,46,51,103 Group 3 Control Lamb Nos. 10,11,18,32,41,49,105,109 All lambs were tagged, weighed and faecal sampled predosing. All lambs were slaughtered at 9 days post treatment and tapeworm and nematode worm counts done on the ' abomasum and small intestine.
Reaction of animals at drenching observed and no effects notice.
EGGS/GRAM 10 DAY CRITICAL DAUGHTER WORM COUNTS Tag No. Wgt Dose Strong. Nem. Strong. Nam. Haem. Osten. Trick Nona. Trick Coop. MONIEZIA kgs mi Scotex Segments mL GROUP 1-LEVITAPE fl (1ml6kg) 17 28 22 26 26 24 102 23 108 32 6.0 150 50 ___ _____ 4.0 200 - 50 _____ .0-- - ___ _____ 50 - 100 ___ _____ 5Λ 50 - 50 - - - - - _ __ 200- - ___ _____ 50- - ___ _____ MEAN 93.76 - 375 GROUP 2 - ALBENDAZOLE Π rnVSkol 12 26 55 50 - 5 - 160 - - - - - 3 10 21 22 45 - - -. - 10 - - - - 5 - 26 28 55 100 - - - 50 - - - - - - 39 24 55 100 - - - 20 - - - - 1 - 43 26 53 150 - 50 - - - - - - 1 5 46 30 65 - - 50 35 51 28 55 100 5 103 20 45 300 - - - 450 - — - — — — — MEAN 1005 - 13.1 - 863 - - - - - 65 11.8 CROUP 3-CONTROL 10 22 100 — 600 — 650 100 — - 700 200 6 110 11 24 250 - 2250 - 1400 400 - - 2200 40002 85 18 22 - - 400 - 880 300 - 100 1800 32002 80 32 30 SO - - - 400 600 - 100 200 300 8 15 41 26 100 - 50 - 50 100 - - 200 .- - - 49 22 50 - 960 - 560 200 - 100 - - - - 105 24 150 - 1400 - 700 100 - - 1600 4800 2 55 109 26 - 1150 - 970 200 - - 800 1400- 40 MEAN 875 850 7013250 375 9375 1738 25 48.1 -ί The tabulated results above show for each result the weights of the lambs, the dose administered, the faecal egg counts predosing and post dosing and the 9 day worm counts. The efficacy of the formulation of Example 1 including minerals and trace elements on Moniezia expansa is demonstrated. The albendazole group results shows efficacy on the common nematodes in lambs is not as high as desired as resistance appears to be present to this active forHaemonchus contortus.
The albendazole was not effective in its efficacy against Monezia expansa. The formulation of Example 1 shows a very successful level of elimination of this tapeworm when in combination with levamisole, with no dimunition in efficacy by levamisole against the common nematodes in lambs.
VARIATIONS ί A range of compositions have been described suitable for 4 the treatment or prevention of helminthiasis in sheep and goats. The trials show dose rates of 3.75 mg/kg of praziquantel and 8mg/kg of levamisole. We have discovered 'that the dose rate Of the formulation of Example 1 can be reduced, thereby reducing the dose rate of praziquantel to about 2mg/kg whilst preventing sheep measles in lambs. Preferred dose rates for lambs and sheep are in the range of 2-7.5 mg/kg of live body weight of praziquantel, giving a comparable range of levamisole of 4-16 mg/kg of live body weight.
Any of the avermectins, ivermectin, moxidectin, doramectin, could be replaced by Milbemycin D or other members of the Milbemycin family (Merck Index 6112, 11th Edition).
Finally it will be appreciated that various other alterations and modifications may be made to the foregoing without departing from the scope of this invention as set forth in the following claims.

Claims (10)

    1. , wherein the formulation is a drench and contains from 0.5 to 15% w/v of praziquantel. 1, wherein the composition includes levamisole, and the composition has a pH of less than 4.0.
  1. » 1. An anthelmintic composition including an effective amount of the anthelmintic praziquantel together with effective amounts of at least one other
  2. 2. , wherein the pH is about 3.0. 15 4. An anthelmintic composition as claimed in claim
  3. 3. An anthelmintic composition as claimed in claim
  4. 4. , wherein the formulation contains levamisole 20 hydrochloride from l to 10% w/v.
  5. 5. An anthelmintic composition as claimed in claim 5 anthelmintic, wherein the other anthelmintic is selected from the group comprising the avermectins; milbemycins; levamisole; tetramisole; or a substituted benzimidazole carbamate, with the proviso that it does not include febantel, pyrantel, oxamniquine nor furapromidium. 10 2. An anthelmintic composition as claimed in claim
  6. 6. An anthelmintic composition as claimed in claim t 4, wherein the formulation contains from 0.05 to 1% w/v of ivermectin or moxidectin or doramectin.
  7. 7. An anthelmintic composition as claimed in claim 25 4, wherein the formulation contains from 1-15% w/v of a benzimidazole chosen from the group comprising mebendazole, fenbendazole, oxfendazole, albendazole, cambendazole, parbendazole, oxibendazole, flubendazole and cyclobendazole.
  8. 8. An anthelmintic composition as claimed in any one of claims 1 to 7, wherein the praziquantel is suspended in a liquid carrier.
  9. 9. An anthelmintic composition substantially as herein described with reference to any one of the Examples.
  10. 10. Use of a composition according to any of the preceding claims in treating helminthiasis in animals.
IE920446A 1991-02-12 1992-02-11 Formulations comprising praziquantel and another anthelmintic IE69667B1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
NZ23708691 1991-02-12

Publications (2)

Publication Number Publication Date
IE920446A1 IE920446A1 (en) 1992-08-12
IE69667B1 true IE69667B1 (en) 1996-10-02

Family

ID=19923486

Family Applications (1)

Application Number Title Priority Date Filing Date
IE920446A IE69667B1 (en) 1991-02-12 1992-02-11 Formulations comprising praziquantel and another anthelmintic

Country Status (3)

Country Link
GB (1) GB2252730B (en)
IE (1) IE69667B1 (en)
NZ (2) NZ247278A (en)

Families Citing this family (71)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BG61064B1 (en) * 1993-08-12 1996-10-31 Илия Илиев Medicamentous form for the deparasitation of animals
DE4400464A1 (en) * 1994-01-11 1995-07-13 Bayer Ag Endoparasiticidal agents
NZ260018A (en) * 1994-03-03 1995-10-26 Bomac Lab Ltd Benzimidazole compositions and anthelmintic compositions
US5387598A (en) * 1994-04-13 1995-02-07 Rossignol; Jean-Francois Composition and galenic formulation suitable for combatting affections of the lower abdomen
AU691990B2 (en) * 1994-11-28 1998-05-28 Virbac S.A. Equine anthelmintic formulations
AUPM969994A0 (en) 1994-11-28 1994-12-22 Virbac S.A. Equine anthelmintic formulations
AU694016B2 (en) * 1995-05-10 1998-07-09 Virbac (Australia) Pty Limited Canine anthelmintic preparation
DE19520275A1 (en) * 1995-06-02 1996-12-05 Bayer Ag Endoparasiticidal agents
US5861142A (en) * 1996-03-25 1999-01-19 Schick; Mary Pichler Method for promoting hair, nail, and skin keratinization
CA2260143C (en) * 1996-07-30 2004-07-13 Ashmont Holdings Limited Anthelmintic formulations
FR2755824B1 (en) * 1996-11-19 1999-01-08 Virbac Sa GALENIC FORMULATION OF BENZIMIDAZOLES FOR TOPICAL USE, PREPARATION METHOD AND USES THEREOF
DE19654079A1 (en) 1996-12-23 1998-06-25 Bayer Ag Endo-ecto-parasiticidal agents
ES2359973T3 (en) 1998-03-19 2011-05-30 MERCK SHARP & DOHME CORP. LIQUID POLYMER COMPOSITIONS FOR THE CONTROLLED RELEASE OF BIOACTIVE SUBSTANCES.
PE20011289A1 (en) * 2000-04-07 2001-12-21 Upjohn Co ANTIHELMINE COMPOSITIONS INCLUDING MACROCYCLIC AND SPIRODIOXEPINOINDOLES LACTONES
DE60118132T2 (en) * 2000-10-10 2006-10-19 Wyeth anthelmintics
US6893652B2 (en) * 2001-08-27 2005-05-17 Wyeth Endoparasiticidal gel composition
US20040151759A1 (en) * 2002-08-16 2004-08-05 Douglas Cleverly Non-animal product containing veterinary formulations
US20050245582A1 (en) 2002-09-12 2005-11-03 The Hartz Mountain Corporation High concentration topical insecticides containing pyrethroids
US7396819B2 (en) 2003-08-08 2008-07-08 Virbac Corporation Anthelmintic formulations
US7671034B2 (en) 2003-12-19 2010-03-02 Merial Limited Stabilized formulation of ivermectin feed premix with an extended shelf life
DK1713468T3 (en) * 2004-02-03 2010-08-16 Wyeth Llc Anthelmintic composition
US7582612B2 (en) 2004-03-12 2009-09-01 Hartz Mountain Corporation Multi-action anthelmintic formulations
EP1734954A4 (en) * 2004-04-07 2007-05-30 Intervet Int Bv Efficacious composition of a benzimidazole, an avermectin and praziquantel and related methods of use
US20060068020A1 (en) * 2004-09-24 2006-03-30 Cottrell Ian W Encapsulated pharmaceutical agents
WO2006061214A1 (en) * 2004-12-10 2006-06-15 Bayer Healthcare Ag Anthelmintic composition
US7348027B2 (en) * 2005-04-08 2008-03-25 Bayer Healthcare Llc Taste masked veterinary formulation
US8362086B2 (en) 2005-08-19 2013-01-29 Merial Limited Long acting injectable formulations
HUE027891T2 (en) 2006-07-05 2016-11-28 Merial Inc 1-Aryl-5-alkyl pyrazole derivative compounds, processes of making and methods of using thereof
LT2639228T (en) 2007-05-15 2016-11-10 Merial, Inc. Aryloazol-2-yl cyanoethylamino compounds, method of making and method of using thereof
EP2222168B1 (en) 2007-11-26 2018-09-12 Merial, Inc. Solvent systems for pour-on formulations for combating parasites
US20110144046A1 (en) * 2008-08-18 2011-06-16 Charles Robert Hillier Anthelmintic compositions
CA2737102C (en) 2008-10-08 2014-02-18 Wyeth Llc Benzimidazole anthelmintic compositions
RS58508B1 (en) 2008-11-14 2019-04-30 Merial Inc Enantiomerially enriched aryloazol-2-yl cyanoethylamino paraciticidal compounds
KR101660068B1 (en) 2008-11-19 2016-09-26 메리얼 인코포레이티드 Compositions comprising 1-arylpyrazole alone or in combination with formamidine for the treatment of parasitic infection
BR112012013482B1 (en) 2009-12-04 2018-11-06 Basf Se bis-organosulfuric compounds pesticides
PL3078664T3 (en) 2009-12-17 2019-08-30 Merial Inc. Antiparasitic dihydroazole compositions
UA108641C2 (en) 2010-04-02 2015-05-25 PARASITICID COMPOSITION CONTAINING FOUR ACTIVE AGENTS AND METHOD OF APPLICATION
WO2013003168A1 (en) 2011-06-27 2013-01-03 Merial Limited Novel insect-repellent coumarin derivatives, syntheses, and methods of use
ES2618813T3 (en) 2011-06-27 2017-06-22 Merial, Inc. Amido-pyridyl ether compounds and compositions and use against parasites
CN103957701B (en) 2011-09-12 2017-05-03 梅里亚有限公司 Parasiticidal compositions comprising an isoxazoline active agent, methods and uses thereof
US20130079394A1 (en) 2011-09-23 2013-03-28 Cnrs (Centre National Recherche Scientifique) Indirect modeling of new repellent molecules active against insects, acarids, and other arthropods
CN104023720B (en) 2011-11-17 2016-10-26 梅里亚有限公司 Comprise the compositions of arylpyrazole and substituted imidazole, its method and purposes
PL3061454T3 (en) 2012-02-06 2021-09-20 Boehringer Ingelheim Animal Health USA Inc. Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof
JO3626B1 (en) 2012-02-23 2020-08-27 Merial Inc Topical compositions comprising fipronil and permethrin and methods of use
EP3453702A3 (en) 2012-04-20 2019-05-15 Merial, Inc. Parasiticidal compositions comprising benzimidazole derivatives, methods and uses thereof
EP2922845B1 (en) 2012-11-20 2018-06-20 Merial, Inc. Anthelmintic compounds and compositions and method of using thereof
PL2950795T3 (en) 2013-01-31 2018-09-28 Merial, Inc. Method for treating and curing leishmaniosis using fexinindazole
NZ719916A (en) 2013-11-01 2017-09-29 Merial Inc Antiparasitic and pesticidal isoxazoline compounds
EP3131398B1 (en) 2014-04-17 2019-10-23 Boehringer Ingelheim Animal Health USA Inc. Use of malononitrile compounds for protecting animals from parasites
US10045979B2 (en) 2014-05-19 2018-08-14 Merial Inc. Anthelmintic compounds
PT3157912T (en) 2014-06-19 2019-06-04 Boehringer Ingelheim Animal Health Usa Inc Parasiticidal compositions comprising indole derivatives, methods and uses thereof
AU2015339096B2 (en) 2014-10-31 2018-08-02 Boehringer Ingelheim Animal Health USA Inc. Parasiticidal composition comprising fipronil
UY36570A (en) 2015-02-26 2016-10-31 Merial Inc INJECTABLE FORMULATIONS OF PROLONGED ACTION THAT INCLUDE AN ISOXAZOLINE ACTIVE AGENT, METHODS AND USES OF THE SAME
US20170020848A1 (en) 2015-04-08 2017-01-26 Merial Inc. Extended release injectable formulations comprising an isoxazoline active agent, methods and uses thereof
UY36683A (en) 2015-05-20 2016-12-30 Merial Inc DEPSIPEPTIDE COMPOUNDS AS ANTHELMINICS
US20160347829A1 (en) 2015-05-27 2016-12-01 Merial Inc. Compositions containing antimicrobial IgY antibodies, for treatment and prevention of disorders and diseases caused by oral health compromising (OHC) microorganisms
UY37137A (en) 2016-02-24 2017-09-29 Merial Inc ANTIPARASITARY COMPOUNDS OF ISOXAZOLINE, INJECTABLE FORMULATIONS OF PROLONGED ACTION THAT INCLUDE THEM, METHODS AND USES OF THE SAME
WO2018039508A1 (en) 2016-08-25 2018-03-01 Merial, Inc. Method for reducing unwanted effects in parasiticidal treatments
WO2018071535A1 (en) 2016-10-14 2018-04-19 Merial, Inc. Pesticidal and parasiticidal vinyl isoxazoline compounds
AU2017361099A1 (en) 2016-11-16 2019-06-06 Boehringer Ingelheim Animal Health USA Inc. Anthelmintic depsipeptide compounds
AU2018292285B2 (en) 2017-06-26 2023-05-25 Boehringer Ingelheim Animal Health USA Inc. Dual active parasiticidal granule compositions, methods and uses thereof
AU2018318945A1 (en) 2017-08-14 2020-03-05 Boehringer Ingelheim Animal Health USA Inc. Pesticidal and parasiticidal pyrazole-isoxazoline compounds
WO2019157241A1 (en) 2018-02-08 2019-08-15 Boehringer Ingelheim Animal Health USA Inc. Parasiticidal compositions comprising eprinomectin and praziquantel, methods and uses thereof
CA3106092A1 (en) 2018-07-09 2020-01-16 Boehringer Ingelheim Pharma Gmbh & Co. Kg Anthelminthic heterocyclic compounds
CN113260419A (en) 2018-11-20 2021-08-13 勃林格殷格翰动物保健美国公司 Indazolyl cyanoethylamino compounds, compositions thereof, methods of making the same, and methods of using the same
AU2020208145B2 (en) 2019-01-16 2023-02-02 Boehringer Ingelheim Vetmedica Gmbh Topical compositions comprising a neonicotinoid and a macrocyclic lactone, methods and uses thereof
JP2022522200A (en) 2019-03-01 2022-04-14 ベーリンガー インゲルハイム アニマル ヘルス ユーエスエイ インコーポレイテッド Chlorthron composition for injection, its method and use
SG11202109786UA (en) 2019-03-19 2021-10-28 Boehringer Ingelheim Animal Health Usa Inc Anthelmintic aza-benzothiophene and aza-benzofuran compounds
CN114144172A (en) 2019-07-22 2022-03-04 英特维特国际股份有限公司 Soft chewable veterinary dosage forms
CA3183100A1 (en) 2020-05-29 2021-12-02 Boehringer Ingelheim Pharma Gmbh & Co. Kg Anthelmintic heterocyclic compounds
AU2021410052A1 (en) 2020-12-21 2023-08-03 Boehringer Ingelheim Vetmedica Gmbh Parasiticidal collar comprising isoxazoline compounds

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2362539C2 (en) * 1973-12-17 1986-05-07 Merck Patent Gmbh, 6100 Darmstadt 2-Acyl-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino [2,1-a] isoquinolines, processes for their preparation and pharmaceuticals containing these compounds
US4303659A (en) * 1979-08-22 1981-12-01 Pfizer Inc. Schistosomicidal compositions
US4447414A (en) * 1982-12-21 1984-05-08 Cutter Laboratories, Inc. Carnivore anthelmintics
DE3705227A1 (en) * 1987-02-19 1988-09-01 Bayer Ag ANTHELMINTHIC ACTIVE COMBINATIONS

Also Published As

Publication number Publication date
NZ247278A (en) 1995-03-28
GB2252730B (en) 1994-12-14
GB9202978D0 (en) 1992-03-25
IE920446A1 (en) 1992-08-12
NZ237086A (en) 1993-07-27
GB2252730A (en) 1992-08-19

Similar Documents

Publication Publication Date Title
IE69667B1 (en) Formulations comprising praziquantel and another anthelmintic
AU695582B2 (en) Anthelmintic formulations
US10449179B2 (en) Stable veterinary anthelmintic formulations
AU2006322120B2 (en) Benzimidazole non-aqueous compositions
AU2009283313B2 (en) Anthelmintic compositions
NZ585223A (en) Anthelmintic composition comprising milbemycin, triclabendazole and a non-surfactant rheology modifier
KR101318603B1 (en) Benzimidazole anthelmintic compositions
NZ515772A (en) Pesticidal emulsion composition containing levamisole in the aqueous phase and an anthelmintic in the organic phase
AU2003203465B2 (en) Anthelminthic Formulation
NZ570591A (en) Anthelmintic compositions
AU2014101200A4 (en) Anthelmintic compositions
EP1713468B9 (en) Anthelmintic composition
CN113260419A (en) Indazolyl cyanoethylamino compounds, compositions thereof, methods of making the same, and methods of using the same
NZ329247A (en) Anthelmintic compositions containing solubilised benzimidazoles such as oxfendazole and a carrier including a pyrrolidone
NZ550279A (en) Medicament
AU2006249206A1 (en) Stable biocidal compositions

Legal Events

Date Code Title Description
SPCF Request for grant of supplementary protection certificate

Free format text: SPC017/2002: 20020722, EXPIRES: 20120213

MM4A Patent lapsed
SPCW Supplementary protection certificate withdrawn

Spc suppl protection certif: SPC017/2002

Filing date: 20020722