EP1560502A1 - Systeme d'administration par voie orale d'un medicament veterinaire et/ou systeme d'administration d'un additif alimentaire, procede de preparation et d'utilisation de ceux-ci - Google Patents

Systeme d'administration par voie orale d'un medicament veterinaire et/ou systeme d'administration d'un additif alimentaire, procede de preparation et d'utilisation de ceux-ci

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Publication number
EP1560502A1
EP1560502A1 EP02788266A EP02788266A EP1560502A1 EP 1560502 A1 EP1560502 A1 EP 1560502A1 EP 02788266 A EP02788266 A EP 02788266A EP 02788266 A EP02788266 A EP 02788266A EP 1560502 A1 EP1560502 A1 EP 1560502A1
Authority
EP
European Patent Office
Prior art keywords
delivery system
feed
feed additive
veterinary drug
active substance
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.)
Withdrawn
Application number
EP02788266A
Other languages
German (de)
English (en)
Inventor
Annamaria Szoke
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
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Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of EP1560502A1 publication Critical patent/EP1560502A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/80—Feeding-stuffs specially adapted for particular animals for aquatic animals, e.g. fish, crustaceans or molluscs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/168—Steroids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/184—Hormones
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/10—Shaping or working-up of animal feeding-stuffs by agglomeration; by granulation, e.g. making powders
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/20—Shaping or working-up of animal feeding-stuffs by moulding, e.g. making cakes or briquettes
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/25—Shaping or working-up of animal feeding-stuffs by extrusion
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals

Definitions

  • the present invention concerns an oral veterinary drug delivery system and/or feed additive delivery system that contains at least one biologically active substance preferably uniformly sorbed into a porous carrier, a method for the preparation of the delivery system, and the application of the product to farmed and pet animals, especially to fish.
  • the oral administration of biologically active substances to animals in feed is a diverse field concerning the type of the delivery system, i. e. the properties of the active substance and the properties of the feed. Another variable i s the distribution of the active substance in the feed, whether it is located throughout the feed or only on its surface.
  • the medicated feed can be prepared by adding the active substance during feed preparation to the feed or combining the active substance with the prepared feed product. Medicated feed can be prepared on farms, in feed mills or by drug and premix manufacturers. Methods for mixing feed ingredients and medication are reported.
  • Chinese patent 1 999- 1 153 12 describes the production of furazolidone- and terramycin-containing fish feed; the drugs are mixed with trace elements, maggot protein, other ingredients of plant origin, and pelleted.
  • Chinese patent 1999- 1 1 1364 describes the preparation of an antiparasitic premix and the usage with fish feed. Abamectin was dissolved in ethanol, mixed with rice husk and dried with hot air. The carrier-drug product was then mixed with the feed ingredients that were fish meal, soy sauce lees, calcium hydrogen phosphate, vitamins and minerals.
  • the recommended preparation of medicated fish feed on farms is surface coating with additional sealing.
  • the procedure is carried out in cement mixers or equivalent equipment: the unmedicated fish feed, the calculated amount of drug, and edible fish oil or vegetable oil are mixed together for several minutes to ensure uniform coating.
  • An example for the preparation of Aquaflor (florfenicol)-containing feed is given on the Syndel International Inc. Aqua Life homepage (www.syndel . com).
  • Tribrissen trimethoprim and sulfadiazine
  • oil is first added to the pellets in the mixer and then the powder is sprinkled into the mixer.
  • Romet-30 (combination of sulphadimethoxine and ormetoprim) is first suspended in edible vegetable oil and the slurry is used to coat the pelleted fish feed.
  • Docosahexaenoic acid and/or its ethyl ester are first mixed with fish oil or vegetable oil and then added to the basic feed.
  • the drug that is concentrated on the surface of the feed spoils the taste of the feed and thus reduces the likeliness of medication ingestion by sick animals with reduced appetite.
  • Experimental scale fish food medication is usually performed by spraying the active ingredient solution onto the food.
  • WO 02/30215 A2 publ i shed patent application that concerns the growing of marine fish in freshwater describes a method for preparing food that contains 7 w/w% sodium chloride and tryptophan.
  • a solution of the calculated amount of sodium chloride and tryptophan was prepared, poured into a hand held sprayer and was then applied to standard freshwater salmonid diet that was rotated in a cement mixer. After absorption of the sodium chloride-tryptophan solution the diet was dried on window screens in a heated rack system. After drying, the pellets were returned to the cement mixer to receive a top dressing that was composed of 50% krill hydrolyzate and 50% Menhaden oil.
  • a spraying process cannot be used safely; the open system is an occupational and environmental hazard.
  • the spraying does not allow the drug solution to penetrate into the feed; the drug is absorbed only into the surface layer.
  • An extra step is required for sealing that involves the use of additional equipment and contamination of the equipment.
  • a clean technology is reported for the preparation of medicated animal foodstuffs in US 6,387,393 that involves the coating of the foodstuff with a cohesive gel containing the drug.
  • the cohesive gel is prepared by mixing the drug with a gelling agent (e.g. cellulose polymer) and other ingredients in a mixer and keeping the dry mixture in sachets. Upon usage the mixture is added to suffi ci ent water to form a suspension for coating the pellets. Pellets are weighed into a suitable mixer (e.g. ribbon blender) and the required amount of drug suspension is added. The mixture is blended for 5 minutes and dispensed into paper sacks. The mixing vessel becomes coated with the gel only to a minimal extent.
  • a gelling agent e.g. cellulose polymer
  • Medicated food for cattle, pigs and fowl can be prepared by this technology.
  • the technology allows for the flexible preparation of medicated foodstuffs and reduces cleaning efforts.
  • the product is not suitable for fish medication; the drug is distributed only on the surface, and the gel coating does not resist leakage.
  • the juveni l e hormone analogue compound 3 -(3 ',7'-dimethyl- octyloxy)pyridine was dissolved in capelin oil for coating the ordinary fish feed pellet for Atlantic salmon in WO 01/07047 A2 published patent application on the control of crustacean infestation of aquatic animals.
  • This method has the advantage that no additional sealing step is required.
  • the application is limited to oil-soluble substances. Efforts have been made for embedding-type or encapsulation-type incorporation of the active substance into the feed.
  • a layered pharmaceutical dosage form for the medication of fish is concerned in WO 89/12442.
  • a drug layer is surrounded with an outer layer that is substantially impermeable to water and the drug, and it contains substances to enhance taste and smell of the product to stimulate the ingestion.
  • the drug layer contains the drug and an aqueous gel-forming carrier material .
  • the dosage form is prepared by co-extruding the outer layer with the medicated inner. Dosage forms of oxytetracycline, flumequine and oxolinic acid for Salmoniformes are claimed.
  • the drug is well enclosed in the system and thus has a low leakage tendency, and is palatable.
  • the drug has to be prepared in advance before knowing the demand. There is also the difficulty of cleaning the extruders in order to avoid cross-contamination.
  • German patent DE I 974 1 1 14 concerns granules, pellets or tablets for veterinary use with a drug-containing core, an inner coating which is acid resistant but soluble at neutral and basic pH values, and an outer coating which is acid labile and insoluble but swellable in neutral and basic media.
  • These compositions are useful for oral administration of antibiotics, vaccines, etc. to fish with the feed; it is placed in the water since the active agent is not immediately released in the water or in the stomach, but is released in the intestine.
  • medicated food has hitherto been prepared principally by two methods: by applying the active substance onto the surface of the carrier after said carrier has been formulated, or by mixing the carrier ingredients with the active substance, thereby introducing said active substance into the mass of the carrier prior to formulation. Both methods have di sadvantages as detailed above.
  • no process for the preparation of medicated foodstuff has been known wherein the active substance is introduced into the bulk of the carrier after the carrier has been formulated.
  • the resulting products have the active material on their surface.
  • Drug substance used to treat and prevent diseases, for contraception, for anesthesia, to increase the resistance of the animal, or to influence its gender.
  • Feed additive substance added to feed to enhance the growth efficiency of the animal, to control parasites, reduce bacterial infections, stimulate certain enzymes, increase appetite, control bloat and feed spoilage.
  • Formulated animal feed feed composed from natural and/or synthetic ingredients as opposed to non-formulated feed and live feed (fish, meat, plants, seeds etc.).
  • Medicated feed feed containing drugs and/or feed additives.
  • Medication, biologically active substance / material drugs and feed additives.
  • Obj ects of the Invention In traditional livestock production as well as in aquaculture the type and amount of required drugs and feed additives cannot be always planned ahead. The same is true for pet animals. There are many factors that affect the usage of medication, e.g. the outbreak of a disease, its type and time; the number of animals that have to be treated; the need for preventive treatment; the hatching rate, litter size, survival rate; the growth stage and weight of the animal that determines the dose, etc.
  • the administration of biologically active substances increases the cost of farming; weak, unhealthy, sick animals are reluctant to ingest drugs orally. Unconsumed and non-absorbed drugs and feed additives pollute the environment.
  • the aim of this invention is to prepare in a flexible manner an oral drug delivery system or feed additive delivery system that contains the biologically active substance in a bioavailable form preferably uniformly sorbed into the bulk of a palatable carrier, preferably animal feed.
  • the medicated feed is prepared from a formulated porous feed that the animal is likely to consume and the medication.
  • the feed On animal farms and aquacultures the feed is usually on hand; the medication can be stored or easily obtained from the manufacturer.
  • drug manufacturers, premix manufacturers and feed mills can produce the medicated feed as orders arrive in a flexible way.
  • the amount of medication that will be included per unit feed can be varied according to the recommended dosage.
  • the medication is preferably uniformly distributed in the feed, not as a coating; thus the palatability of the feed is not altered.
  • the sorption of the medication within the feed assures that no leaching or only insignificant leaching occurs.
  • the method for the preparation allows for laboratory scale, pilot scale and production scale. Closed systems are used at any scale, thus occupational and environmental hazards are excluded.
  • the present invention relates to an easily ingestible and bioavailable oral veterinary drug delivery system and feed additive delivery system which contains the medication preferably uniformly sorbed into the bulk of a porous carrier, preferably feed, and is simply prepared by mixing the solution of the medication with the feed to allow for sorption, followed by the evaporation of the solvent.
  • the process is flexible and can be carried out in laboratory, pilot and industrial scale when need for medication occurs.
  • the technology involves closed systems, e.g. rotary evaporators, drum dryers, thus occupational and environmental hazards are excluded.
  • the product can be used for the medication of farmed animals and pets, preferably in aquaculture.
  • the medication is sorbed within the pores; it is adhered to the feed and thus it is not likely to leak easily into the environment. In those cases when the carrier contains lipophilic substances, the low wettability delays the leaching of the drug as well.
  • the present invention relates to an oral veterinary drug delivery system and/or feed additive delivery system comprising at least one biologically active substance sorbed at least to a substantial extent into the bulk of a carrier and which is obtainable by the steps: a) making available the solution of the biologically active substance and the carrier in a vessel; b) mixing the content of the vessel for a time period sufficient for the sorption of at least a substantial part of the biologically active substance into the carrier, preferably for 10 minutes to 2 hours, more preferably 20 to 30 minutes to promote sorption of the solution of the biologically active substance by the carrier; and c) evaporating the solvent while maintaining mixing until dryness.
  • the terms "at least to a substantial extent/ at least a substantial part of the biologically active substance” means at least 40 w/w%, preferably at least 60 w/w%, more preferably 80 w/w%, even more preferably 90 w/w% and most preferably up to 100 w/w% of the active substance.
  • novel product according to the present invention is a medicated feed that, as a result of the above described preparation process, contains the active substance uniformly sorbed into the bulk of the feed matrix, unlike products that were prepared by applying the biologically active substance onto the surface of the formulated carrier.
  • the skilled person will readily be able to make a distinction between products prepared by premixing the active substance with the carrier prior to formulation and the product according to the present invention e.g. on the basi s of the differences between their active substance distribution profile.
  • the biologically active substance is uniformly sorbed into the carrier.
  • the solvent is selected from the group consisting of acetone, methanol, ethanol, propanol, isopropanol, ethyl acetate, halogenated hydrocarbons, water and any solvent of the active substance having a boiling point of less or equal to 120 °C, and their mixtures.
  • the solvent is evaporated in vacuum and/or in an air or nitrogen stream.
  • mixing is carried out in a vessel selected from the group consisting of rotary evaporator, mixing vessel, agitated vessel, drum dryer, vacuum drum dryer and fluid bed.
  • process steps a) to c) are performed in a closed system.
  • the carrier is a porous material.
  • the carrier is a formulated animal feed selected from the group of feed pellets, granules, extrudates, tablets, flakes and other particulate feed in dry, semi- moi st or moist state.
  • the carrier is a palatable substance for animals.
  • the biologically active substance is selected from the group consisting of parasiticides, anthelmintics, antibacterial agents, antistress agents, animal growth promoters, anti-inflammatory agents, antibiotics, hormones, hormone analogues, oral vaccines, vitamins and any other drugs, and any pharmaceutically acceptable combinations thereof.
  • the biologically active substance is selected from the group consisting of 17- alpha-methyltestosterone, 17-alpha-ethyltestosterone, 17-alpha-methyl- dihydrotestosterone, 17-beta-estradiol, flumequine, oxolonic acid, sarafloxacin, oxytetracycline, sulfadimethoxine, sulfamonomethoxine, ormetoprim, sulfamerazine, ampicillin, penicillin, enrofloxacin, buserelin, chloramphenicol, furazolidone, gentamycin, ivermectin, hexaflumuron, levamisole, metronidazole, nalidixic acid, nitroxynil, nitrofurazone, piromidic acid, streptomycin, sulf
  • the biologically active substance is a hazardous material for the environment and/or the operating personnel.
  • the biologically active substance is radiolabeled.
  • the oral veterinary drug delivery system and/or feed additive delivery system according to the present invention has good storage stability.
  • no or low leaching of the active substance can be experienced from the oral veterinary drug delivery system and/or feed additive delivery system according to the present invention.
  • the oral veterinary drug delivery system and/or feed additive delivery system according to the present invention is bioavailable.
  • the second aspect of the present invention is a process for the preparation of the oral veterinary drug delivery system and/or feed additive delivery system as disclosed above comprising the steps of a) making available the solution of the biologically active substance and the carrier in a vessel; b) mixing the content of the vessel for a time period sufficient for the sorption of at least a substantial part of the biologically active substance into the carrier, preferably for 10 minutes to 2 hours, more preferably 20 to 30 minutes, to promote sorption of the solution of the biologically active substance by the carri er; and c) evaporating the solvent while maintaining mixing until dryness.
  • the solvent is selected from the group consisting of acetone, methanol, ethanol, propanol, isopropanol, ethyl acetate, halogenated hydrocarbons, water and any solvent of the active substance having a boiling point of less or equal to 120 °C, and their mixtures.
  • the solvent is evaporated in vacuum and/or in an air or nitrogen stream.
  • mixing is carried out in a vessel selected from the group consisting of rotary evaporator, mixing vessel, agitated vessel, drum dryer, vacuum drum dryer and fluid bed.
  • steps a) to c) are performed in a closed system.
  • the third aspect of the present invention is the oral veterinary drug delivery system and/or feed additive delivery system as disclosed above for use as a pharmaceutical or feed additive.
  • the oral veterinary drug delivery system and/or feed additive delivery system as disclosed above is for use in aquaculture, especially farming of fish, farming of poultry, swine, cattle, and for pet animals.
  • the HPLC system included two Model 125 programmable pumps, a
  • Methyltestosterone was determined by reverse phase HPLC using a 3 ⁇ m C 1 8 column (Supelco LC18-DB 15cm x 4.6 mm) and a gradient elution program.
  • Mobile phase A was a mixture of 40 volumes methanol, 30 volumes acetonitrile, and 50 volumes water.
  • Mobile phase B included 40 volumes methanol, 30 volumes acetonitrile, and 10 volumes water.
  • the program was 0-5 min. 100% A; 5- 12 min. linear gradient to 40% A, 60% B; 12- 15 min. linear gradient to 100% A; 15-20 min. 100% A.
  • Flow rate was set to 1 mL/min. Under these conditions the methyltestosterone peak appeared at 1 1 min and was separated from matrix components and possible metabolites.
  • Flumequine was analyzed on the same HPLC system using isocratic elution.
  • the mobile phase was composed of 60 volumes buffer (20 mM potassium phosphate, pH 3.2), 20 volumes methanol and 20 volumes tetrahydrofuran.
  • the C 18-column was Beckman Ultrasphere IP, 25cm x 4.6 mm. The flumequine peak appeared at 9.5 mm.
  • Calibration curves for the methyltestosterone determinations were prepared from standard solutions of 17 ⁇ -methyltestoserone and of possible metabolites 4-androsten- 17 ⁇ -methyl-l l ⁇ , l l ⁇ -diol-3-one and ⁇ -4, 6-andro- stadien- 17 ⁇ -methyl - 17 ⁇ -ol-3-one in mobile phase A.
  • Plasma samples were analyzed using an isotope dilution method.
  • a cold spike that contained known amounts of the analyte (17 ⁇ -methyl- testosterone or flumequine and their possible metabolites) was added to the radioactive samples, and the specific activity was calculated from the HPLC quantification and the corresponding peak radioactivities.
  • S x was A dpm /A ana i yte , where Aanaiyte was the amount of analyte as determined by HPLC using the calibration curves, and A dpm was the amount of radioactivity in the corresponding HPLC eluate fractions.
  • Rainbow trout (Oncorhynchus mykiss), average weight 500 g, equal amounts of male and female were selected from a 1000 L fiberglass aquarium. Fish were housed individually in 75 L rectangular glass aquaria that were operated in a flow through state at a constant 15 ⁇ 1 °C temperature. A photoperiod of 12 h light and 12 h dark was maintained. Fish were fed daily with Rangen soft-moist trout feed (Rangen Feed, Buhl, ID) at a rate of 0.5 or 1 % body weight up to the day before medication or surgical experimentation.
  • Rangen soft-moist trout feed Rangen soft-moist trout feed (Rangen Feed, Buhl, ID) at a rate of 0.5 or 1 % body weight up to the day before medication or surgical experimentation.
  • the amount of active substance that was introduced into the feed was calculated in such a manner that the daily dose was included in a fraction of the daily feed ration.
  • Medicated feed pellets were prepared according to Example 1. After removal of the round-bottom flask from the rotavapor, nitrogen was purged through the content of the flask.
  • the weight of the methyltestosterone feed product was 96.64 g.
  • methyltestosterone content was evaluated. The average of the three samples was 20.02 ⁇ 0.604 mg methyltestosterone/g feed (CN - 3.02%).
  • the medicated feed was administered prior the non-medicated feed.
  • MF daily medicated feed
  • C M concentration of medication in the feed (mg/g).
  • TF (g) N x fish body weight (g)
  • N 0.005 or 0.01.
  • the amount of non-medicated feed (NF) was:
  • NF (g) TF - MF.
  • the oral bioavailability of methyltestosterone was determined using the areas under the respective intraarterial (i. a.) and oral plasma (p. o.) concentration-time curves as described by the equation
  • Example 7 Storage stability of the methyltestosterone feed
  • Methyltestosterone feed prepared according to Example 1 was tested for storage stability. Aliquots were placed into three tared crystallization dishes, covered and stored at 4°C. The contents of two dishes were used for controlling the loss of weight during storage at 4°C. Weight loss was checked at the following times after medicated feed preparation: 3 days, 1 , 3 , 4, 9 weeks, 3 , 7 months. The losses of weights were 0.123 % and 0.091 % respectively after 7 months of storage. The methyltestosterone concentration in the feed was checked in the freshly prepared feed and at different times thereafter. Three one-gram samples were measured at each time the feed consistency was checked as described in Example 3. Table 2 shows the average of these three samples.
  • the methyltestosterone concentration after 7 months storage was measured as 1 .30 mg/g or 6.49 % less than on the day of the feed preparation.
  • Flumequine feed preparation For flumequine feed preparation the procedures in Examples 1 and 2 were followed. Unlabeled flumequine was from Sigma Chemical Co. St. Luis, MO; ⁇ 2- 14 C]-flumequine was supplied by Amersham International Pic Buckinghamshire, UK. 100 g Rangen moist trout feed (4 mm) was treated with a total of 0.9004 g of labeled and unlabeled flumequine that was dissolved in 300 mL acetone. The concentration of flumequine in the product was 8.70 ⁇ 0.219 mg flumequine/g feed.
  • Veterinary drugs and feed additives are usually added to the feed either directly during the preparation of the feed; or the medication is added to the feed product in a later step.
  • the present invention provides a drug delivery system where the medication is preferably uniformly distributed through the porous feed in a stable form; a gentle treatment of the porous carrier with the solution of the medication allows for at least 90-97% recovery of the drug/feed additive.
  • Another disadvantage of adding the medication to the feed ingredients during feed preparation is that the whole production line is contaminated with the drug/feed additive. This includes such apparatuses that are difficult to clean, e.g. mixers, extruders, and other pelleting machines.
  • the present invention when the feed is treated with the drug solution in a separate process, only designated equipment get in contact with the active ingredient(s). Moreover, the cleaning of a vacuum evaporator glass bottle or the drum of a vacuum dryer is a relatively simple procedure.
  • Additional disadvantage of medicating feed during feed preparation is that there is no flexibility in the quality and quantity of the drug delivery product once it is prepared.
  • the present method allows for great flexibility: as demand occurs, the appropriate type and amount of medication can be added to the desired carrier using a fast and simple method.
  • the drug delivery system with preferably uniformly sorbed medication in a feed carrier can be prepared on farms, in feed mills or by premix and drug manufacturers.
  • the product is a drug delivery system that is composed of a feed core coated with the medication.
  • weak, unhealthy, sick animals are reluctant to ingest such drug-tasting feed. Therefore, tedious and more expensive delivery systems (inj ections, patches) are the alternative.
  • the medication is not accumulated on the surface; the animals are offered a palatable drug delivery system with the usual feed taste. If it is offered as the initial part of the feeding regime, the animal will most probably consume at least those initial feed portions that are medicated.
  • Previous methods for adding medication to feed include mixing the feed and the drug in open mixers, e.g. cement mixers, or spraying the feed with the drug solutions or suspensions. Both methods are hazards for the environment and for the operating personnel.
  • the present invention offers a method that is carried out in a closed system thus being environmentally and occupationally safe. The importance of a closed system is even more pronounced when radiolabeled compounds are used e.g. for experimental purposes.
  • Using spraying for coating the feed with medication does not ensure uniform distribution of the drug.
  • the present method results in preferably uniform sorption of the drug into the carrier.
  • Scale up from a small-scale rotary evaporator is readily accomplished, e.g. by using a Buchi vacuum evaporator from 20 mL to 50 L volume, and for larger batches a vacuum drum dryer.

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Husbandry (AREA)
  • Birds (AREA)
  • Health & Medical Sciences (AREA)
  • Endocrinology (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Insects & Arthropods (AREA)
  • Fodder In General (AREA)
  • Medicinal Preparation (AREA)
  • Feed For Specific Animals (AREA)

Abstract

L'invention concerne un système d'administration par voie orale d'un médicament vétérinaire et/ou un système d'administration d'un additif alimentaire renfermant au moins une substance active sur le plan biologique, de préférence, uniformément sorbée au moins jusqu'à un certain point dans le volume d'un véhicule poreux, de préférence, un aliment; le système d'administration d'un médicament ou d'un additif alimentaire peut être obtenu par mélange de l'aliment avec une solution de la substance active sur le plan biologique aux fins de sorption, suivie de l'évaporation du solvant. L'invention concerne également des procédés de préparation du système de médicament vétérinaire ou d'additif alimentaire et des utilisations de celui-ci comme produit pharmaceutique ou additif alimentaire. La préparation est effectuée dans un système fermé et sûr au niveau professionnel et environnemental. Les produits selon l'invention peuvent être utilisés pour des animaux d'élevage et des animaux de compagnie, de préférence des poissons d'élevage d'eau douce ou d'eau de mer.
EP02788266A 2002-10-31 2002-12-19 Systeme d'administration par voie orale d'un medicament veterinaire et/ou systeme d'administration d'un additif alimentaire, procede de preparation et d'utilisation de ceux-ci Withdrawn EP1560502A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
HU0203718 2002-10-31
HU0203718A HUP0203718A2 (hu) 2002-10-31 2002-10-31 Orális adagolású, állatgyógyászati hatóanyagot tartalmazó készítmény, és/vagy táplálékkiegészítő készítmény, eljárás annak előállítására és annak alkalmazása
PCT/HU2002/000152 WO2004039172A1 (fr) 2002-10-31 2002-12-19 Systeme d'administration par voie orale d'un medicament veterinaire et/ou systeme d'administration d'un additif alimentaire, procede de preparation et d'utilisation de ceux-ci

Publications (1)

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EP1560502A1 true EP1560502A1 (fr) 2005-08-10

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EP02788266A Withdrawn EP1560502A1 (fr) 2002-10-31 2002-12-19 Systeme d'administration par voie orale d'un medicament veterinaire et/ou systeme d'administration d'un additif alimentaire, procede de preparation et d'utilisation de ceux-ci

Country Status (6)

Country Link
EP (1) EP1560502A1 (fr)
CN (1) CN100426980C (fr)
AU (1) AU2002353246A1 (fr)
HU (1) HUP0203718A2 (fr)
NO (1) NO20052011L (fr)
WO (1) WO2004039172A1 (fr)

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CN102928558A (zh) * 2012-10-30 2013-02-13 四川新希望畜牧科技有限公司 制备甲基紫示踪物的方法

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CN1722956A (zh) 2006-01-18
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CN100426980C (zh) 2008-10-22
WO2004039172A1 (fr) 2004-05-13
NO20052011L (no) 2005-05-30
HUP0203718A2 (hu) 2004-08-30

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