GB2354710A - Paracetamol solution in polyethylene glycol and/or polypropylene glycol for farm animals - Google Patents

Paracetamol solution in polyethylene glycol and/or polypropylene glycol for farm animals Download PDF

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Publication number
GB2354710A
GB2354710A GB0018504A GB0018504A GB2354710A GB 2354710 A GB2354710 A GB 2354710A GB 0018504 A GB0018504 A GB 0018504A GB 0018504 A GB0018504 A GB 0018504A GB 2354710 A GB2354710 A GB 2354710A
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United Kingdom
Prior art keywords
paracetamol
feed
water
animals
composition
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Granted
Application number
GB0018504A
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GB0018504D0 (en
GB2354710B (en
Inventor
Frederic Lucas
Stephen Payan
Jose Daoudal
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Sogeval SA
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Sogeval SA
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Publication of GB2354710A publication Critical patent/GB2354710A/en
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Publication of GB2354710B publication Critical patent/GB2354710B/en
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    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • 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
    • 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
    • A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
    • 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
    • A23K50/70—Feeding-stuffs specially adapted for particular animals for birds
    • A23K50/75—Feeding-stuffs specially adapted for particular animals for birds for poultry
    • 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
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers

Abstract

An antipyretic composition for treating farm animals such as pigs, poultry or calves comprises a non-aqueous solution of 15-25% w/w paracetamol in polyethylene glycol and/or polypropylene glycol, preferably 20% w/w in PEG 200 and/or polypropylene glycol. The solution is for incorporation e.g. by spraying into animal feed or dilution with drinking water. The composition may contain 40-85% w/w polyethylene glycol and 0-45% w/w polypropylene glycol, and/or up to 5% excipients e.g. appetite enhancing agents. A process for incorporation of the composition into drinking water on a farm equipped with a water-circulation unit connected to a water reservoir includes determining the desired amount of composition, adding the composition and agitating. Intermediate dilution may be carried out in a mother solution, with a metering pump to control the amount of mother solution added to the water reservoir. Alternatively, granulated feed may be sprayed with the composition after manufacture of the feed, the amount being determined by desired concentration in the feed and flow rate of the feed in a hopper.

Description

2354710 The present invention relates to an antipyretic composition for
veterinary use suitable for the treatment of factory farm animals intended for human consumption, in particular pigs, poultry or calves.
For reasons of public safety, which will be easily understood, veterinary active ingredients that can be administered to animals intended for human consumption have to satisfy very strict standards and must be registered. on a positive list which may be modified.
At present, only one antipyretic molecule is offered,in veterinary medicine, namely aspirin. However, that molecule has a certain number of disadvantages well known to specialists, including its ulcerogenic character which excludes any long-term treatment of livestock.
In addition, the aspirin molecule is distinguished by poor stability and a marked tendency to hydrolyse, both in aqueous solution and when it is incorporated in powdered form in granulated feed; therefore, it tannot be stored in a ready-for-use Galenical form and has to be absorbed very rapidly after it has been prepared.
It has also recently been discovered that aspirin can cause in children a very serious degen eration of the liver known as Reye's syndrome, which tends to discourage its use in paedi-' atric medicine.
Owing to those various disadvantages, it is desirable for there to be available to veterinary surgeons an antipyretic active ingredient which can be substituted for aspirin.
To that end. there has been proposed accordina, to the invention the paracetamol molecule or 4-hydroxyacetanilide of the formula:
HO 0 N CH3 H 2 the use of which is very widespread in human medicine but the antipyretic properties of which are not currently used in the veterinary field.
Various experiments carried out on animals have demonstrated the antipyretic efficiency of the paracetamol molecule and its harmlessness; it has, in particular, been established that this molecule does not enerate dangerous residues in tissue, which means that the animal treated can be consumed immediately without observing a delay period between the end of treatment and slaueliter.
The absence of toxicity and the quality of the paracetamol molecule having thus been demonstrated, it remained to develop paracetamol-based antipyretic formulations presented in Galenical forms suitable for collective treatments.
The Galenical forms of the paracetamol-based antipyretic formulations proposed in human medicine (water-dispersible or soluble forms. in particular tablets or effervescent powders, or syrups having a low concentration of paracetarnol) are not suitable for the veterinary M I field and. in particular. for the treatment of farm animals. In fact, basically only two Galenical forms are possible in that particular field.
The first of those forms corresponds to a medicinal premix which is to be added to solid feed for livestock in factories approved by the Authorities.
The preparation of such a medicinal premix does not present any particular problem given that the addition of paracetamol in powdered form to wheat flour or corn flour results in a stable product. However. that Galenical form is not always entirely satisfactory because it excludes ariv selective treatment of alven farm animals: the feed containincr the medicinal premix is stored in a silo on the farm and is therefore necessarily consumed by all the farm animals until the stock is exhausted.
3 The second of the possible Galenical forms of a paracetamol-based formulation corresponds to a concentrated solution which is to be incorporated in the animals' feed, in particular in their drinking water, or which is to be sprayed onto granulated feed.
Such a Galenical form. which constitutes the subject-matter of the present invention. has numerous advantages and is, in particular, entirely adaptable to the needs of animals but its development involves the resolution of numerous problems and is therefore particularly complicated.
It is known that paracetamol is very poorly water-soluble at ambient temperature: it is more soluble in hot water but recrystallises as soon as the solution cools. It is also known that paracetamol hydrolyses and oxidises in an aqueous medium. Therefore, it is not possible to preserve aqueous solutions of paracetamol.
At the same time it should be noted that. in the case of a drinkable solution which is to be incorporated in the animals' drinking water. for economic reasons associated with the larsze volumes of water which would then be necessarv. that Galenical form cannot be offered ready for use but must necessarily be prepared by the breeder. before administration. from a soluble powder or from a concentrated solution that can be diluted.
Furthermore. farms are conventionally equipped with circulation circuits for the animals' drinkin!z water which supply troughs adapted to relatively large animals. such as pigs or calves. or small pipettes more especially adapted to poultry: as a general rule. the circuiation circuits are activated automatically by control devices associated. in particular. with level probes placed in the troughs. or with devices detecting the presence of an animal.
The ob-lect accordin!z to the invention is to propose a paracetamo I based antipyretic cornnosition which can be either incorporated in the water provided by those circulation circ;jts or spraved onto granulated feed. That requirement excludes any presentation of the comnosition in the form of a powder. bearing in mind the poor solubility of paracetamol in 4 water at ambient temperature. because the clogging of various elements of the circulation circuit (control devices, pipettes...) would then be almost inevitable.
The object of the present invention is therefore to propose an antipyretic composition for veterinary use which is suitable for the treatment of factory farm animals intended for human consumption, in particular pigs, poultry or calves, and which is in the Galenical form of a concentrated solution which is stable and soluble in cold water in any proportion required for those treatments, the solution being capable of being introduced into the circulation circuits for the animals' drinking water which are provided on numerous farms, or of being sprayed onto granulated feed.
It has surprisingly been possible to satisfy all those requirements by dissolving the paracetamol in a solvent which appears on the positive list giving the substances whose use is authorised in veterinary medicine. namely a low-molecular-weight polyethylene glycol and/or polypropylene glycol.
The invention therefore relates to an antipyretic composition. characterised in that it is constituted by a drinkable solution containing from 15 to 25% by weiaht, preferably approximately 20% by weight. of paracetarnol dissolved in a solvent constituted by a low- molecular-weight polyethylene 2lycol and/or polypropylene glycol.
The solution accordina to the invention contains. preferabiv in proportions by weight. from 40 to 85% of polyethylene crlvcol and from 0 to 45% of polypropylene glycol.
Accordinsi to the invention. the composition may. where appropriate. contain up to 517C of excipients. for example appetite-enhancing agents, or antioxidants or preservatives.
The low-molecular-weight polyethylene glycol which can be used according to the invention must have a sufficiently low viscosity and will as a general rule be from PEG 150 to PEG 300: it has been possible to achieve particularly satisfactory results usincr PEG 200.
The antipyretic composition accordina to the invention is distinguished by its stability in 17 aqueous solution at any concentration but also by its stability over time and by the absence of any degradation phenomenon or precipitation phenomenon even after prolonged storaae.
In order to verify that last property, a study was carried out on the variations in the paracetamol concentration over a period of storacre of 42 months at ambient temperature, on the one hand. and at a temperature of 37C. on the other hand. of compositions according to the invention initially containing 20% by weight of paracetamol dissolved in polyethylene glycol 200.
The test was carried out on three batches of compositions. A. B and C.
The results obtained are compiled in the following Tables.
6 BATCH A T=O T+6 months T+9 months T+12 T+18 T+24 T+30 T+36 T+42 months months months months months months Ambient t. 20.18 19.51 19.87 20.34 20%61 107 19.39 21.00 19.31 370C 20.18 19.53 19.74 20.87 20.58 19.81 19.66 19.57 19.08 BA,rCH B T=O T+6 months T+9 months T+12 T+18 T+24 T+30 T+36 T+42 months months months months months months Ambient t. 21.08 19.51 19.76 21.04 20.51 19.70 21.63 19.25 37')C 21.08 19.43 19.56 20.94 20.63 20.53 19.46- 19.79 19.31 BATCH C T=O T+6 Months T+9 months T+12 T+18 T+24 T+30 T+36 T+42 months months months months months. months Ambient t. 21.32 19.43 19.95 20.01 20.82 20.22 18.45 22.10 19.60 370C 21.32 19.52 19.89 20.13 20.91 21.18 19.67 20.11 19.29 w 7 The Tables prove that the paracetamol concentration of the composition according to the invention has remained practically unchanged over time and remains at the initial value approximately 10%.
The present invention relates also to a process for. incorporating the above-mentioned antipyretic composition -in animal drinking water on a farm equipped with a water-circulation circuit which can be activated automatically by means of control devices associated, in particular, with level probes or with devices detecting the presence of an animal.
According to the invention, the first step in such a-process is to determine a desired concentration of paracetamol in the drinking water, taking into account the prescribed dosage, the growth tables and also the average water consumption of the animals to be treated.
The desired concentration having thus been determined, it is advantageous then to add to thi-circulation circuit the amount of concentrated solution of paracetamol dissolved in a polyol of the above-mentioned type that enables that concentration to be obtained at the troughs or the pipettes where the animals to be treated come to quench their thirst.
According to a first variant of the invention, the water-circulation circuit with which the farm is equipped is connected to a lar ge reservoir containing the amount of water necessary for a group of animals for a specific period, in particular one day.
According to that first variant of the invention. after determining the desired concentration of paracetamol in the drinking water: the arriount of concentrated solution that has to be added to the water contained in the reservoir to obtain drinking water having that paracetamol concentration is calculated, - said amount of concentrated solution is introduced into the reservoir, and - the diluted solution so obtained is agitated.
According to a second variant of the invention, the farm's watercirculation circuit is connected to the water mains.
8 According to that second variant of the invention, a suppllv duct which. on the one hand, is connected to a tank receiving a mother solution having an intermediate paracetarnol concentration and which, on the other hand. comprises a metering pump having a specific metering ratio, is connected to the water-circulation circuit, and after predefining the desired concentration of paracetamol in the drinki no, water:
D I- - a calculation is carried out to establish what the concentration of the mother solution present in the tank must be to obtain drinking water having that concentration, taking the metering ratio of the metering pump into account.
- a calculation is carried out to establish how the concentrated solution must be diluted to obtain the mother solution, - such a mother solution having an intermediate paracetamol concentration is prepared by dilutinthe concentrated solution and it is introduced into the tank.
That variant of the irfvention. accordinc, to which the concentrated solution of paracetamol dissolved in a low-molecular-weight polyethylene glycol undergoes two successive dilutions. is particularly advantageous.
Within the scope of that variant. it is of course necessary for the paracetamol-based formulation to be completely solubilised. at all stages of dilution. in order to exclude any risk of clogging the watercirculation circuit. It should be noted that such clogging could, in particular. occur in the metering pump supply tube. which extends to the bottom of the tank containin(a the mother solution. in the metering pump and also in the control devices permitting the automatic activation of the water-circulation circuit and the pipettes when the solution is intended for poultry.
Accordina to the invention, the metering pump has. as a general rule. a metering ratio of the order of from 1% to 51-c and mav advantaaeousiv be a commercial pump whose metering ratio is adjustable.
9 It should be noted that such a metering pump can, after rinsing, be used for introducing other medicinal active products (antibiotics... into the animals' drinking water.
It has been established that, for farm animals, the dose'.which should be prescribed is, as a,general rule, 30 mg of paracetamol per kg live weight per day.
Taking into account the growth tables and the average water consumption of the animals to be treated, it was determined that, on the one hand, in the case of broilers, the concentration of paracetamol in the drinking water should be of the. order of from 75 to 225 mg per litre, which, if using 4 2% metering pump, corresponds to a mother solution containing from 3.75 to 11.25 g of paracetamol/litre and that-, on the other hand, in ' the case of pigs, the concentration of paracetamol in the drinking water should be of the order of from 300 to 500 mg per litre, which, if a 2% metering pump is used, corresponds to a mother solution containing from 15 to 25 g of paracetamol per litre.
The use of a concentrated solution of paracetamol dissolved -in a lowmolecular-weight polyethylene glycol to 20% clearly enables those data to be observed.
In the case of a circulation circuit connected to a reservoir having a capacity of 1000 litres, it' would thus be necessary to provide for the addition to the reservoir of from 375 ml to 2.5 litres of concentrated solution, while, in the case of a circulation cirouit connected to the water mains and equipped with a 2% metering pump, it would be necessary to provide for the addition of from 1835 ml to 125 ml of concentrated solution per litre of mother solution.
Those figures show that the antipyretic composition according to the invention is entirely suitable for the use for which it is intended.
The present invention relates also to a process for incorporating the above-mentioned antipyretic composition in the animals' diet by sprayinar it onto granulated feed.
According to that process, the antipyretic composition is sprayed onto the feed at the end of I the latter's manufacturing process at the factory, using a spray device especially in a hopper which is equipped with spray nozzles and in which the granulated feed flows by gravity in order to supply an emptying device. such as a lorry or a conveyor belt.
It is important not to spray the antipyretic composition onto the feed until after manufacture has.been completed, so that the composition does not undergo the thermal or mechanical treatments which the granulated feed undergoes in the course of manufacture.
The process also has the advantage that it makes it possible to confine the spray treatment to Z only a specific amount of granulated feed as a function of the user's demand, and to deliver it to him, by way of example, in a compartmentalised lorry in order to treat only diseased animals, which are then isolated.
Accordina to another feature of the process. a desired concentration of paracetarnol in the 2ranulated feed is determined, taking into account the prescribed dosage. the growth tables and also the average feed consumption of the animals to be treated, the amount of antipyretic composition that has to be sprayed is determined as a function of the amount of feed to be treated. especially by measuring the flow rate of the granulated feed which flows in the hopper. and the spray device is controlled in response thereto.

Claims (10)

  1. I Antipyretic composition for veterinary use suitable for the treatment of factory farm animals intended for human consumption, in particular pigs, poultry or calves, characterised in that it is constituted by a concentrated and stabilised non-aqueous solution which, on the one hand. is to be incorporated in the animals' feed, in particular in their drinking water, or sprayed onto granulated feed, and, on the other hand, contains from 15 to 25% by weight, preferably approximately 20% by weight, of paracetamol (4-hydroxyacetanilide) dissolved in a solvent constituted by a low-molecular-weight polyethylene glycol, preferably by PEG 200 and/or polypropylene glycol.
  2. 2. Composition according to claim 1, characterised in that it contains, in proportions by welzht, from 40 to 85% of polyethylene glycol and from 0 to 45% of polypropylene glycol.
  3. 3. Composition according to either claim I or claim 2. characterised in that it contains up to 5% of excipients. for example appetite-enhancing agents.
  4. 4. Use of a concentrated and stabilised non-aqueous solution containing from 15 to 25% by weight, preferably approximately 20% by weight, of paracetamol (4-hydroxvacetanilide) dissolved in a solvent constituted by a low-molecular-weight polyethylene glycol, preferably by PEG 200 and/or by polypropylene glycol, for the preparation of an antipyretic composition for veterinary use which is suitable for the treatment of factory farm animals for human consumption. especially pigs. poultry or calves. and which is to be incorporated in the animals' feed. in particular in their drinking water. or which is to be sprayed onto granulated feed.
  5. 5. Process for incorporating the antipyretic composition accordin2 to any one of claims I to 3 in the animal drinkina water on a farm equipped with a water-circulation circuit which. on the one hand. can be activated automatically by means of control devices and which. on the other hand. is connected to a reservoir containing the amount of water necessary for a group of animals for a specific period. in particular for one day.
    12 characterised in that: - a desired concentration of paracetamol in the drinking water is determined, taking into account the prescribed dosage, the growth tables and also the average water consumption of the animals to be treated. - the amount of concentrated solution that has to be added to the water contained in the reservoir to obtain drinking water having the desired paracetamol concentration is calculated, - said amount of concentrated solution is introduced into the reservoir, and - the diluted solution so obtained is agitated.
  6. 6. Process for incorporating the antipyretic composition according to any one of claims I to 4 in the animal drinking water on a farm equipped with a water-circulation circuit which, on the one hand, can be activated automatically by means of control devices and which, on the other hand. is connected to the water mains. characterised in that: - a supply duct which. on the one hand, is connected to a tank which is to receive a mother solution of paracetamol and which. on the other hand, comprises a metering pump having a z:I specific metering ratio is connected to the water-circulation circuit, - a desired concentration of paracetamol in the drinking water is determined, takinc, into account the prescribed dosage. the growth tables and also the average water consumption of the animals to be treated.
    - a calculation is carried out to establish what the concentration of the paracetamol mother solution present in the tank must be to obtain drinking water having the desired paracetamol concentration. taking the metering ratio of the metering pump into account, - a calculation is carried out to establish how the concentrated solution must be diluted to obtain the mother solution.
    - such a mother solution havina an intermediate paracetamol concentration is prepared by diluting the concentrated solution and it is introduced into the tank.
  7. 7. Process accordinc, to claim 6. characterised in that the metering pump has a metering ratio of the order of from I T to 5
  8. 8. Process according to either claim 6 or claim 7, characterised in that the metering pump is a commercial pump whose metering ratio is adjustable.
  9. 9. Process for incorporating the antipyretic composition according to any one of claims I to 4 in the diet of animals by spraying it onto granulated feed. characterised in that the antipyretic composition is sprayed ont o the feed at the end of the latter's manufacturing process at the factory, using a spray device especially in a hopper which is equipped with spray nozzles and in which the aranulated feed flows bv - ravity in order to supply an emptying device, such as a lorry,or a conveyor belt.
  10. 10. Process according to claim 9. characterised in that - a desired concentration of paracetamol in the granulated feed is determined, taking into account the prescribed dosage, the growth tables and also the average feed consumption of the animals to be treated.
    - the amount of antipyretic composition that has to be sprayed is determined as a function of the amount of feed to be treated. especially by measuring the flow rate of the granulated feed which flows in the hopper. and - the spray device is controlled in response thereto.
GB0018504A 1999-07-29 2000-07-27 Paracetamol solution in polyethylene glycol and/or polypropylene glycol for farm animals Expired - Lifetime GB2354710B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR9909840A FR2796843B1 (en) 1999-07-29 1999-07-29 CONCENTRATED AND STABILIZED ANTIPYRETIC COMPOSITION FOR VETERINARY USE INTENDED TO BE INCORPORATED IN ANIMAL FEEDING AS WELL AS A METHOD OF INCORPORATING THIS COMPOSITION INTO ANIMAL BEVERAGE WATER

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GB0018504D0 GB0018504D0 (en) 2000-09-13
GB2354710A true GB2354710A (en) 2001-04-04
GB2354710B GB2354710B (en) 2004-05-12

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BE (1) BE1012818A3 (en)
CA (1) CA2316731C (en)
DE (1) DE10037121B4 (en)
DK (1) DK177041B1 (en)
ES (1) ES2336164B1 (en)
FR (1) FR2796843B1 (en)
GB (1) GB2354710B (en)
HU (1) HU230460B1 (en)
IT (1) IT1318645B1 (en)
NL (1) NL1015790C2 (en)
PL (1) PL221309B1 (en)
RU (1) RU2218154C2 (en)

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CN107669634A (en) * 2016-09-30 2018-02-09 青岛大学 A kind of paracetamol oral spray and preparation method thereof

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RU2736423C1 (en) * 2020-04-24 2020-11-17 Федеральное государственное бюджетное научное учреждение "Поволжский научно-исследовательский институт производства и переработки мясомолочной продукции" (ГНУ НИИММП) Method of using non-steroidal anti-inflammatory preparations "paracetam - avz" and "ketokvin 10 %" in breeding of replacement chicks of parent flock of chickens

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EP0441307A1 (en) * 1990-02-06 1991-08-14 Showa Yakuhin Kako Co., Ltd. Syrup composition
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HUP0002994A3 (en) 2008-04-28
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ES2336164B1 (en) 2011-01-24
PL221309B1 (en) 2016-03-31
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FR2796843A1 (en) 2001-02-02
HU0002994D0 (en) 2000-10-28
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RU2218154C2 (en) 2003-12-10
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