WO2005016356A1 - Formulations anthelminthiques ameliorees - Google Patents

Formulations anthelminthiques ameliorees Download PDF

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Publication number
WO2005016356A1
WO2005016356A1 PCT/US2004/025000 US2004025000W WO2005016356A1 WO 2005016356 A1 WO2005016356 A1 WO 2005016356A1 US 2004025000 W US2004025000 W US 2004025000W WO 2005016356 A1 WO2005016356 A1 WO 2005016356A1
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WO
WIPO (PCT)
Prior art keywords
formulation
ivermectin
active ingredient
pyrantel
docsl
Prior art date
Application number
PCT/US2004/025000
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English (en)
Inventor
Ian William Cottrell
Arimas Das Nandy
Albert Ahn
Richard Fisher
Original Assignee
The Hartz Mountain Corporation
Chanelle Pharmaceuticals Manufacturing Ltd.
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
Priority claimed from US10/637,807 external-priority patent/US7396819B2/en
Application filed by The Hartz Mountain Corporation, Chanelle Pharmaceuticals Manufacturing Ltd. filed Critical The Hartz Mountain Corporation
Publication of WO2005016356A1 publication Critical patent/WO2005016356A1/fr

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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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin

Definitions

  • the invention relates generally to anthelmintic formulations which can have significant parasiticidal activity as anthelmintics, ectoparasiticides, insecticides and acaricides in animal health and more particularly to solid anthelmintic formulations containing ivermectin.
  • ivermectin is hygroscopic and therefore tends to be undesirably unstable. It has also been seen that ivermectin is unstable in both acidic and basic solutions and is susceptible to photodegradation and oxidative degradation. Accordingly, it is very difficult to prepare a solid composition, such as a tablet, containing ivermectin without having to resort to using a large amount of filler material to make up the bulk of the tablet in order to maintain the integrity of the compound and even then, degradation problems can exist. This problem is compounded when additional drugs are intended to be included in the same formulation, as ivermectin can degrade or be degraded by other drugs.
  • a multidrug anthelmintic formulation in solid form that can be formed into a solid or tablet of optimal size, palatable to animals and which can be easily administered to the affected animal.
  • a pharmaceutical formulation for use in the treatment of helminthiasis of mammals, and particularly tapeworm, hookworm, roundworm, whipworm and heartworm of domestic animals and farm animals. Accordingly, the present invention provides a method of treating helminthiasis in mammals, which method comprises administering to the mammal in need thereof, an anthelmintically effective amount of a pharmaceutical formulation of the invention.
  • the present invention also provides a composition and a method for preparing a pharmaceutical formulation containing ivermectin and a method and composition that can contain ivermectin plus other active compositions such as hexahydropyrazinoisoquinolines, anthelmintic pyrimidines such as tetrahydropyrimidines and benzimidazoles or probenzimidazoles.
  • active compositions such as hexahydropyrazinoisoquinolines, anthelmintic pyrimidines such as tetrahydropyrimidines and benzimidazoles or probenzimidazoles.
  • An example of a hexahydropyrazinoisoquinoline is praziquantel
  • an example of a tetrahydropyrimidine is a pyrantel, such as pyrantel pamoate.
  • An example of a benzimidazole is fenbendazole.
  • One preferred method involves isolating the ivermectin through granulation, in particular, spray granulation.
  • the other drugs can also be granulated or spray granulated.
  • the granules can be left in a powder form, tabletted or packed into a capsule (i.e., encapsulated).
  • One method of preparation of the formulation comprises the following steps:
  • SSL-DOCSl l 8 3 769vl (a) preparing a first and second; a first, second and third or a first, second, third and fourth (or more) combination including the first and second; the first, second and third or the first, second, third and fourth active ingredient, respectively;
  • the present invention relates to anthelmintic active compound combinations including avermectins or macrolide endectocides, hexahydropyrazinoisoquinolines, anthelmintic pyrimidines such as tetrahydropyrimidines and benzimidazoles or probenzimidazoles.
  • Acceptable tetrahydropyrimidines include, for example, pyrantel, morantel and oxantel.
  • An acceptable pyrantel that may be used is pyrantel pamoate.
  • Acceptable hexahydropyrazinoisoquinolines include, for example, praziquantel.
  • Acceptable macrolide endectocides include, for example, avermectins.
  • Acceptable avermectins include, for example, ivermectin, doramectin, selamectin and abamectin.
  • SS -DOCSl 148 3 769vl include, for example, mebendazole, oxibendazole, fenbendazole, oxfendazole, triclabendazole, flubendazole, ricobendazole, thiabendazole, and albendazole.
  • Acceptable probenzimidazoles include, for example, febantel.
  • a formulation of active ingredients comprising ivermectin, praziquantel, pyrantel (pamoate) and fenbendazole or febantel is particularly preferred.
  • the active ingredients target different pathogenic organisms that can adversely affect the health of a mammal.
  • ivermectin kills a variety of internal and external parasites; a number of worms including stomach worms, intestinal worms, lungworms, barber's worms, lice and mites. This particular combination is particularly effective in fighting a wide variety of organisms.
  • an active ingredient e.g. a benzimidazole or ivermectin
  • an active ingredient is intended to cover pharmaceutically active forms thereof such as salts, hydrochlorides, chelates, and so forth.
  • the formulation may also be useful in overcoming problems seen with single drug resistance.
  • the inclusion of greater than one anthelmintic in the formulations discussed herein may have an increased likelihood of eliminating a particular helminth that is resistant to other included anthelmintic compounds. Even if the helminth is resistant to one, two or three of the ingredients, it is likely that at least one of the other ingredients will be effective at eliminating the helminth in question.
  • the disease or group of diseases described generally as helminthiasis is due to infestation of an animal host with parasitic worms known as helminths.
  • Helminthiasis is a prevalent and serious economic problem in domesticated animals such as swine, sheep, horses, cattle, goats, dogs, cats and poultry.
  • the group of worms described as nematodes causes widespread and often times serious infection in various species of animals.
  • Still other parasites may be located in other tissues and organs of the body such as the heart and blood vessels, subcutaneous and lymphatic tissue and the like.
  • the parasitic infections known as helminthiases lead to anemia, malnutrition, weakness, weight loss, severe damage to the walls of the intestinal tract and other tissues and organs and, if left untreated, may result in death of the infected host.
  • the antiparasitic agents of this invention find their primary use in the treatment and/or prevention of helminthiasis, they are also useful in the prevention and treatment of diseases caused by other parasites, for example, arthropod parasites such as ticks, lice, fleas, mites and other biting insects in domesticated animals and poultry. Repeat treatments are given as required to combat re-infestations and are dependent upon the species of parasite. The techniques for administering these materials to animals are known to those skilled in the field of veterinary medicine.
  • the preparations are suitable for combating pathogenic endoparasites which occur in animal husbandry and animal breeding in productive, breeding, zoo, laboratory, experimental animals and pets, and have a favorable toxicity to warm-blooded animals. In this connection, they are active against all or individual stages of development of the pests and against resistant and normally sensitive species.
  • pathogenic endoparasites it is intended that disease, cases of death and reduction in production (for example in the production of meat, milk, wool, hides, eggs, etc.) are reduced so that more economic and simpler animal husbandry is possible by means of the use of the pharmaceutical formulation.
  • Productive and breeding animals include mammals, such as, for example, cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer and reindeer, pelt animals, such as, for example, mink, chinchilla and raccoons, birds, such as, for example, chickens, geese, turkeys and ducks, fresh and salt-water fish, such as, for example, trout, carp and eels, and reptiles.
  • mammals such as, for example, cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer and reindeer
  • pelt animals such as, for example, mink, chinchilla and raccoons
  • birds such as, for example, chickens, geese, turkeys and ducks
  • fresh and salt-water fish such as, for example, trout, carp and eels, and reptiles.
  • Laboratory and experimental animals include mice, rats, guinea pigs, hamsters, dogs and cats.
  • Pets include dogs and cats.
  • the formulation according to the invention is particularly preferably administered to dogs and cats, but is suitable for other mammals.
  • Administration can take place both prophylactically and therapeutically .
  • formulations can be administered directly or in the form of suitable preparations, enterally, parenterally or dermally.
  • Enteral administration of the formulations takes place, for example, orally in the form of powder, tablets, capsules, pastes, potions, granules, orally administered solutions, suspensions and emulsions, boli, medicated feed or drinking water.
  • Suitable preparations are : oral solutions and concentrates for oral administration after dilution; emulsions and suspension for oral administration; and semisolid preparations; formulations in which the active compound is processed in an ointment base or in an oil-in-water or water-in-oil emulsion base; solid preparations, such as powders, premixes or concentrates, granules, pellets, tablets, caplets, boli and capsules, with tablets the preferred form;
  • SSL-DOCSl 148 3 769vl oral solutions are prepared by dissolving the active compound in a suitable solvent and, if appropriate, adding additives such as solubilizers, acids, bases, buffer salts, antioxidants and preservatives. The solutions are filtered and packed under sterile conditions.
  • Solvents may include: physiologically acceptable solvents, such as water, alcohols, such as ethanol, butanol, benzyl alcohol, glycerol, propylene glycol and polyethylene glycol, N-methylpyrrolidone, and mixtures of the same.
  • physiologically acceptable solvents such as water
  • alcohols such as ethanol, butanol, benzyl alcohol, glycerol, propylene glycol and polyethylene glycol, N-methylpyrrolidone, and mixtures of the same.
  • the active compounds can, if appropriate, also be dissolved in physiologically acceptable vegetable or synthetic oils.
  • Solubilizers may include: solvents which promote dissolution of the active compound in the main solvent or substances which prevent precipitation of the active compound. Examples are polyvinyl pyrrolidone, polyoxyethylated castor oil and polyoxyethylated sorbitan esters.
  • One particularly preferred formulation of the invention comprising four active ingredients, is preferably administered in the form of capsules, more preferably tablets.
  • a preferred formulation of the present invention contains 0.005 - 25% ivermectin, preferably 0.01 - 15%, and most preferably 0.012 - 5%, with 0.013 or 0.016% as a preferred example.
  • a preferred formulation of the present invention can contain 2.0 - 58% of a secondary anthelmintic drug, such as an isoquinoline, preferably praziquantel, preferably 6 - 41%, and most preferably 8.2 - 23%, with 8.7% or 10.56% as a preferred example.
  • a preferred formulation of the present invention can contain 1.5 - 76% of an anthelmintic pyrimidine, preferably pyrantel, such as pyrantel pamoate, preferably 11.2 - 52%, and most preferably 21.2 - 33%, with 25.04%> or 30.40% as a preferred example.
  • a preferred formulation of the present invention can contain 25.3 - 62.5% of a benzimidazole, preferably fenbendazole, preferably 30.0 - 45.2%, and most preferably 35.3% as a preferred example.
  • a benzimidazole preferably fenbendazole, preferably 30.0 - 45.2%, and most preferably 35.3% as a preferred example.
  • a preferred formulation of the present invention can contain 15.2 -37.6 % of a probenzimidazole, preferably febantel, preferably 19.4 - 31.6%, and most preferably 21.4%.
  • a preferred dosage of avermectin is about 5 - 7 ⁇ g/Kg body weight of the animal administered monthly, preferably 5.5 - 6.5 ⁇ g/Kg body weight, with 6 ⁇ g/Kg body weight as a preferred example.
  • a preferred dosage of anthelmintic pyrimidines, e.g., pyrantel pamoate, is about 4.25 - 5.75 mg/Kg body weight administered monthly, preferably 4.75 - 5.25 mg Kg, with 5 mg as a preferred example.
  • a preferred dosage of hexahydropyrazinoisoquinaline is about 4.25 - 5.75 mg/Kg body weight administered monthly, preferably 4.75 - 5.25 mg/Kg, with 5 mg as a preferred example.
  • a preferred dosage of benzimidazole, e.g., fenbendazole is about 37 - 63 mg/Kg body weight administered monthly, preferably 42 - 58 mg/Kg, with 50 mg as a preferred example.
  • a preferred dosage of febantel is about 18 - 32 mg/Kg body weight administered monthly, preferably 21 - 29 mg/Kg, with 25 mg as a preferred example.
  • the active compound should be mixed with suitable excipients, if appropriate, with addition of auxiliaries, and converted to the form desired.
  • One preferred method of preparation of the formulation comprises the following steps: (a) preparing a first and second; a first, second and third or a first, second, third and fourth (or more) combination including the first and second; the first, second and third or the first, second, third and fourth active ingredient, respectively;
  • SSL-DOCSl 148 3 769vl (c) granulating one or all of the solutions, especially by spray granulation, from (b) by combining with a dry combination;
  • Spray granulation involves the spraying of liquid (i.e., solution, suspension melt and so forth) onto a powder or granules while simultaneously building particle size and removing the volatile liquid by drying.
  • liquid i.e., solution, suspension melt and so forth
  • the active By mixing an active ingredient with a carrier in the liquid phase, the active can become "encapsulated” or substantially covered in a matrix of carrier after the spray granulation process.
  • Granulation is generally performed by spraying liquid into the fluidized powder. The granules can subsequently be dried with heated air.
  • Suitable excipients may include physiologically acceptable inert solids such as, for example, sodium chloride, calcium carbonate, hydrogen carbonates, aluminum oxides, silicas, clays, precipitated or colloidal silicon dioxide and phosphates.
  • excipients may include, for example, sugar, cellulose, Croscarmellose Sodium (i.e., carboxymethyl cellulose), Aerosil, nutrients and feedstuff ' s, such as milk powder and pork liver powder, animal meals, ground and crushed cereal meals, Avicel PHI 02 and starches.
  • Auxiliaries can include preservatives, antioxidants and colorants.
  • auxiliaries can include lubricants, such as, for example, magnesium stearate, stearic acid, talcum and bentonites, disintegration-promoting substances, such as starch or transversely crosslinked polyvinyl pyrrolidone, binders, such as, for example, starch, gelatin or linear polyvinyl pyrrolidone, and dry binders, such as microcrystalline cellulose.
  • lubricants such as, for example, magnesium stearate, stearic acid, talcum and bentonites
  • disintegration-promoting substances such as starch or transversely crosslinked polyvinyl pyrrolidone
  • binders such as, for example, starch, gelatin or linear polyvinyl pyrrolidone
  • dry binders such as microcrystalline cellulose.
  • the formulation can also be in the form of a chewable, such as a beef- chewable containing ground or minced beef or other meat, in addition to other excipients listed above.
  • carrier material The materials in the final formulation, such as the excipients, auxiliaries, synergists and other materials, which aid in delivery, shelf-life, desired physical structure and so forth will be referred to herein generally as carrier material.
  • carrier material could be pharmaceutically active under certain circumstances.
  • EXAMPLE 1 Preparation of Tablets or Caplets Containing Ivermectin. Praziquantel. Pyrantel and Fenbendazole
  • Russel Sieve fitted with 20# sieve and collected in a stainless steel drum (a) Avicel PH102 (b) Croscarmellose Sodium
  • citrate buffer solution was placed on a hot plate and heated to a temperature of 55 ⁇ 5° C.
  • Granulation was continued by spraying 300g of purified water at room temperature. Additional purified water was sprayed until the desired consistency was achieved.
  • SSL-DOCSl 148 37 69vl 9,000g of purified water with the impeller and the chopper set on low speed. Additional purified water was added to achieve the good granular mass.
  • the granulated mixture was dried using a fluid bed drier and transferred to a double polythene lined suitable container.
  • Russel Sieve fitted with 20# sieve and collected in a stainless steel drum (a) Praziquantel USP (b) Povidone (c) Croscarmellose Sodium (d) Avicel PH102
  • the delumped material was mixed in a drum tumbler for 20 minutes.
  • the mixture was added to a Diosna mixer and 10 L of purified water was gradually added with the impeller on low speed with the chopper activated for 5 minutes.
  • the choppers were set on fast speed and run for 3 minutes.
  • the granules were dried in a fluid bed drier and transferred to a double polythene lined suitable container.
  • SSL-DOCSl 1483769vl stirred with medium agitation until the components had completely dissolved. The resulting
  • Eudragit solution was allowed to settle until the air bubbles had escaped.
  • the praziquantel fenbendazole granulated mixture was added to the spray granulator and coated with the Eudragit E-100 solution. The resulting material was transferred to a double polythene lined suitable container.
  • the first four excipients were sifted through a 500# sieve and collected in a suitable container. Then the Magnesium Stearate was sifted through a 500# mesh sieve. The four mixtures containing the active ingredients of the formulation (i.e., Mixtures A, B and C) and the excipient mixture were blended in a drum tumbler for 25 minutes. The sifted Magnesium Stearate was added and blended for an additional 5 minutes. [0063] The formulation was then either compressed into tablets or caplets of 1800 mg or 3600 mg or the granules were packaged into sachets.
  • EXAMPLE 2 Preparation of Tablets or Caplets Containing Ivermectin. Praziquantel. Pyrantel and Febantel
  • Russel Sieve fitted with 20# sieve and collected in a stainless steel drum (a) Avicel PHI 02 (b) Croscarmellose Sodium (c) Povidone
  • the delumped material resulting from the step above was added to the drum tumbler and blended for 20 minutes.
  • Purified water was added to a stock pot with citric acid and sodium citrate dihydrate. The contents were mixed for 5 minutes with a stirring rod.
  • Polyethylene glycol flakes were added to a separate stock pot and heated with a water bath to a temperature of 50-65° C to melt the flakes. The solution was maintained at this temperature. Ivermectin was added to the melted polyethylene glycol with gentle stirring until the compound was dissolved. The solution was maintained at 50-65° C.
  • citrate buffer solution was placed on a hot plate and heated to a temperature of 55 ⁇ 5°C.
  • Granulation was continued by spraying 300g of purified water at room temperature. Additional purified water was sprayed until the desired consistency was achieved.
  • the granulated mixture was dried using a fluid bed drier and transferred to a double polythene lined suitable container.
  • Russel Sieve fitted with 20# sieve and collected in a stainless steel drum (a) Praziquantel USP (b) Povidone (c) Croscarmellose Sodium (d) Avicel PHI 02
  • the delumped material was mixed in a drum tumbler for 20 minutes.
  • the mixture was added to a Diosna mixer and 10 L of purified water was gradually added with the impeller on low speed with the chopper activated for 5 minutes.
  • the choppers were set on fast speed and run for 3 minutes.
  • the granules were dried in a fluid bed drier and transferred to a double polythene lined suitable container.
  • Russel Sieve fitted with 20# sieve and collected in a stainless steel drum (a) Avicel PH102 (b) Croscarmellose Sodium (c) Povidone
  • the granulated mixture was dried using a fluid bed drier and transferred to a double polythene lined suitable container.
  • Russel Sieve fitted with 20# sieve and collected in a stainless steel drum (a) Praziquantel USP (b) Povidone (c) Croscarmellose Sodium (d) Avicel PHI 02
  • SSL-DOCSl 1483769vl four mixtures containing the active ingredients of the formulation (i.e., Mixtures G, H and I) and the excipient mixture were blended in a drum tumbler for 25 minutes. The sifted Magnesium Stearate was added and blended for an additional 5 minutes. [00118] The formulation was then either compressed into tablets or caplets of 1800 mg or 3600 mg or the granules were packaged into sachets.
  • Russel Sieve fitted with 20# sieve and collected in a stainless steel drum (a) Avicel PHI 02 (b) Croscarmellose Sodium (c) Povidone
  • Ivermectin was added to the ethanol with gentle stirring at room temperature until the compound was dissolved.
  • SSL-DOCSl 1483769vl [00131] The following materials (in the order listed below) were passed through a
  • the granulated mixture was dried using a fluid bed drier and transferred to a double polythene lined suitable container.
  • Russel Sieve fitted with 20# sieve and collected in a stainless steel drum (a) Praziquantel USP (b) Povidone (c) Croscarmellose Sodium (d) Avicel PHI 02
  • SSL-DOCSl 1483769vl The delumped material was mixed in a drum tumbler for 20 minutes. The mixture was added to a Diosna mixer and 28,684g of isopropyl alcohol was gradually added with the impeller on low speed with the chopper activated for 5 minutes. The choppers were set on fast speed and run for 3 minutes. The granules were dried in a fluid bed drier and transferred to a double polythene lined suitable container. [00139] Excipient Mixture:
  • Magnesium Stearate was added and blended for an additional 5 minutes.
  • the formulation was then either compressed into tablets or caplets of 1800 mg or 3600 mg or the granules were packaged into sachets.

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

Abstract

La présente invention concerne un procédé de préparation d'une formulation pharmaceutique contenant de l'ivermectine et un procédé et une composition contenant de l'ivermectine ainsi que des hexahydropyrazinoisoquinolines, des tétrahydropyrimidines et des benzimidazoles ou du fébantel. Des exemples d'hexahydropyrazinoisoquinolines, de tétrahydropyrimidines et de benzimidazoles comprennent respectivement le praziquantel, le pamoate de pyrantel et le fenbendazole. Cette invention se rapporte également à une formulation pharmaceutique destinée à être utilisée dans le traitement de l'helminthose chez les mammifères et notamment le ténia, l'ankylostome, le ver rond, le trichure et la filaire des chiens chez les animaux domestiques et les animaux de ferme. La présente invention concerne également une méthode de traitement de l'helminthose chez les mammifères, ladite méthode consistant à administrer au mammifère nécessitant un tel traitement, une quantité efficace du point de vue anthelminthique d'une formulation pharmaceutique selon l'invention.
PCT/US2004/025000 2003-08-08 2004-08-03 Formulations anthelminthiques ameliorees WO2005016356A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US10/637,807 2003-08-08
US10/637,807 US7396819B2 (en) 2003-08-08 2003-08-08 Anthelmintic formulations
US10/800,407 US7396820B2 (en) 2003-08-08 2004-03-12 Anthelmintic formulations
US10/800,407 2004-03-12

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WO2005016356A1 true WO2005016356A1 (fr) 2005-02-24

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1734954A1 (fr) * 2004-04-07 2006-12-27 Intervet International BV Composition efficace d'un benzimidazole, d'une avermectine et de praziquantel et procedes d'utilisation associes
WO2008148027A1 (fr) * 2007-05-25 2008-12-04 First Priority, Inc. Combinaison antiparasitaire et procédé permettant de traiter des animaux domestiques
WO2011027333A1 (fr) * 2009-09-07 2011-03-10 Douglas Robert Cleverly Préparations anthelmintiques granulées
GB2475701A (en) * 2009-11-26 2011-06-01 Michael Hilary Burke An orally administered anthelmintic unit dose and process for the preparation thereof
US9233100B2 (en) 2012-02-06 2016-01-12 Merial, Inc. Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof
US11285101B2 (en) 2012-04-04 2022-03-29 Intervet Inc. Soft chewable pharmaceutical products

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4814347A (en) * 1985-07-22 1989-03-21 The Upjohn Company Anthelmintic spiroketals and method of use
US5036069A (en) * 1987-02-19 1991-07-30 Bayer Aktiengesellschaft Anthelmintic active compound combinations
US5945317A (en) * 1996-08-30 1999-08-31 Merck & Co., Inc. Antiparasitic agents

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4814347A (en) * 1985-07-22 1989-03-21 The Upjohn Company Anthelmintic spiroketals and method of use
US5036069A (en) * 1987-02-19 1991-07-30 Bayer Aktiengesellschaft Anthelmintic active compound combinations
US5945317A (en) * 1996-08-30 1999-08-31 Merck & Co., Inc. Antiparasitic agents

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1734954A4 (fr) * 2004-04-07 2007-05-30 Intervet Int Bv Composition efficace d'un benzimidazole, d'une avermectine et de praziquantel et procedes d'utilisation associes
EP1734954A1 (fr) * 2004-04-07 2006-12-27 Intervet International BV Composition efficace d'un benzimidazole, d'une avermectine et de praziquantel et procedes d'utilisation associes
WO2008148027A1 (fr) * 2007-05-25 2008-12-04 First Priority, Inc. Combinaison antiparasitaire et procédé permettant de traiter des animaux domestiques
AU2020202781B2 (en) * 2009-09-07 2021-05-13 Argenta Innovation Limited Granulated anthelmintic preparations and delivery systems
WO2011027333A1 (fr) * 2009-09-07 2011-03-10 Douglas Robert Cleverly Préparations anthelmintiques granulées
AU2022200149B2 (en) * 2009-09-07 2023-06-15 Argenta Innovation Limited Granulated anthelmintic preparations and delivery systems
US20120238516A1 (en) * 2009-09-07 2012-09-20 Douglas Robert Cleverly Granulated anthelmintic preparations and delivery systems
US11253593B2 (en) 2009-09-07 2022-02-22 Argenta Innovation Limited Granulated anthelmintic preparations and delivery systems
GB2475701A (en) * 2009-11-26 2011-06-01 Michael Hilary Burke An orally administered anthelmintic unit dose and process for the preparation thereof
GB2475701B (en) * 2009-11-26 2011-10-19 Michael Hilary Burke A process for the preparation of an orally administered anthelmintic unit dose tablet
US9931320B2 (en) 2012-02-06 2018-04-03 Merial Inc. Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof
US10596156B2 (en) 2012-02-06 2020-03-24 Boehringer Ingelheim Animal Health USA Inc. Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof
US9259417B2 (en) 2012-02-06 2016-02-16 Merial, Inc. Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof
US9233100B2 (en) 2012-02-06 2016-01-12 Merial, Inc. Parasiticidal oral veterinary compositions comprising systemically-acting active agents, methods and uses thereof
US11285101B2 (en) 2012-04-04 2022-03-29 Intervet Inc. Soft chewable pharmaceutical products
US11337917B2 (en) 2012-04-04 2022-05-24 Intervet Inc. Soft chewable pharmaceutical products

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