ES2336164A1 - Paracetamol solution in polyethylene glycol and/or polypropylene glycol for farm animals - Google Patents

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

Concentrated antipyretic composition and stabilized for veterinary use intended for incorporation into the Food and drink (water) of animals.

The present invention relates to a veterinary antipyretic composition suitable for treatment of livestock animals intended for human consumption, particularly pigs, poultry and calves.

For public safety reasons easy to understand, veterinary active ingredients authorized for administration to animals intended for human consumption must meet very strict standards and must be registered in a positive list that can be modified.

Currently in veterinary medicine it is proposed a single antipyretic preparation, aspirin. Said compound nevertheless it has a certain number of problems well known by specialists among which, we can highlight its ulcergenic character that excludes any prolonged treatment of won.

In addition, the aspirin compound is characterized by having weak stability and a marked tendency to hydrolysis, both in aqueous solutions and in powder form incorporated into granulated foods. It cannot be stored in a Galenic form ready for use and must be absorbed with a lot Speed once it has been prepared.

Moreover, it has recently been discovered that aspirin can cause degeneration in children very severe liver called "Reye's syndrome" which It has motivated its use in pediatric medicine.

These different inconveniences make It is advisable for veterinarians to have a principle antipyretic active that can replace aspirin.

According to this invention, we have the idea of propose, for this purpose, the paracetamol molecule or formula 4 hydroxy-acetanilide:

one

whose use is very widespread in human medicine, but whose properties Antipyretics are not currently used in the field of veterinary

Different experiments with animals have allowed to demonstrate the antipyretic efficacy of the molecule of paracetamol and its harmless character; in particular, we were able establish that said molecule does not generate hazardous waste in tissues, which makes the treated animal can be consumed from immediate mode, without respecting a time between the end of the treatment and its sacrifice.

The quality and absence of toxicity of the paracetamol molecule have already been demonstrated, it remains to elaborate paracetamol-based antipyretic formulas that are presented under Galenic forms adapted for collective treatments.

The galenic forms of formulations Paracetamol-based antipyretics proposed in human medicine (hydro dispersible or soluble formulas, in particular tablets in effervescent powders or even syrups with a concentration weak in paracetamol) have not adapted to the veterinary field and in particular to the treatment of farm animals. Indeed, in that particular field essentially no more can be found than two galenic preparations.

The first of these forms corresponds to a drug preparation or mixture intended to be added to the solid feed for livestock in factories that have The permission of the authorities.

The preparation of said drug mixture does not it involves particular difficulties since adding paracetamol in powder form such as cornmeal or wheat flour It leads to a stable product. So far, this galenic form it is not totally satisfactory since it excludes everything timely treatment of certain farm animals: Indeed, the Food containing the drug mixture is stored in the inside a silo in the farmer's house and therefore must be compulsorily consumed by all animals in the hatchery until That stock runs out.

The second of the galenic formulas of a Paracetamol-based formulation as proven appropriate to a concentrated solution intended for incorporation into the feeding of animals, in particular to the water they drink or to be sprayed on granulated foods.

Said galenic form, which constitutes the object of the present invention, it has numerous advantages and in particular is perfectly adaptable to the needs of animals although reaching that point implies the resolution of numerous problems and it is particularly complicated.

Indeed, it is well known that paracetamol It is very poorly soluble in water at room temperature, it is easier in hot water, but it crystallizes again when the solution is cools On the other hand, it is known that paracetamol oxidizes and hydrolyzes in aqueous media. Therefore, the possibility of conserve aqueous solutions of paracetamol.

In parallel, it should be noted that, in the case of a drinkable solution intended for incorporation into the water of animals, due to economic reasons linked to the importance of the volumes of water that would be necessary, this galenic form does not can be offered ready for employment, but must be prepared by the farmer before being administered to from a soluble powder or a concentrated solution that can be diluted

Farms are traditionally equipped with water circulation circuits so animals can drink that feed batteries adapted to animals of size relatively important such as pigs or the cattle (calves) or a small bathtub more especially adapted to birds. These circulation circuits are, as a rule general, automatically activated by devices command particularly associated with level probes placed inside the batteries or even to detecting devices of the presence of animals

In accordance with the present invention, an attempt is made propose an antipyretic composition based on paracetamol and that can be incorporated into the water provided by the circuits of circulation, and be sprayed on granulated foods (feed). This requirement excludes any submission of a composition in the form of a powder, taking into account the poor solubility of paracetamol in water at room temperature: filling of the different elements of the circulation circuit (pipettes, command devices etc.) would then be almost inevitable.

The present invention also has as its object, propose a veterinary antipyretic composition suitable for the treatment of intensive livestock animals, intended for human consumption, in particular of pigs, poultry or calves, which It is presented in the galenic form of a concentrated solution stable and soluble in cold water in all the necessary proportions for such treatments, which can be introduced into the circuits of water circulation for animals where it can be at provision of numerous individuals or being sprayed on granulated foods.

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For a better understanding of this patent, accompanies a sheet with diagrams diagrams in which:

Fig. 1 represents the first execution sheet of the invention: incorporation of the antipyretic solution to water of watering cattle in which:

-1º.- It is a ring road circuit of Water.

-2º.- It is a water tank to water for a day the cattle.

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Fig. 2 represents the second form of embodiment of the invention: incorporation of the solution water antipyretic watering with dosing pump and duct of adduction, in which:

1º.- It is a water circulation circuit.

2º.- It is the water distribution network.

3º.- It is a dosing pump.

4º.- It is a bucket with stock solution.

5º.- It is the conduit of adduction.

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Fig. 3 represents the incorporation of the antipyretic solution to spray granulated foods in which:

1º.- It is the entrance of granulated food to the hopper.

2nd.- It is the hopper with spray ducts in which granulated foods are sprayed as they fall in the hopper Spraying at the end of the manufacturing process of the food.

3º.- It is the evacuation device; truck or feed conveyor belt.

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Fig. 4 represents the first phase of the system dosing, in which the water inlet A drives the piston B which dragged through the outlet of the mixture, at the same time the dosing piston D sucks the product and injects it inside of the homogenization chamber. At the end of the route, raise the intake valves (2a) and the exhaust valves are closed (1st).

Fig. 5 represents the second phase of said dosing system in which the piston (B) descends and a part of the solution is injected into the chamber of homogenization At the end of its path the exhaust valves (1a) open and the intake valves (2a) close again and The cycle starts again.

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An amazing way to satisfy all these imperatives to dissolve paracetamol in a substance that appears in the positive list that lists the substances whose use It is allowed in veterinary medicine, namely: A Polyethylene low molecular weight glycol and / or polypropylene glycol.

The invention object of this patent makes reference to an antipyretic composition characterized by being constituted by a drinkable solution with a content of between 15 and 25% by weight, preferably with an approximate 20% weight of paracetamol dissolved in a solvent composed of polyethylene low molecular weight glycol and / or polypropylene glycol.

The solution according to the invention contains, preferably weighted proportions of between 40 and 85% of polyethylene glycol and 0 to 45% polypropylene glycol.

According to the invention, this composition can, if necessary, contain up to 5% of excipients, as per example appetite agents or even antioxidants or preservatives

Low molecular weight polyethylene glycol to be used according to the invention must be sufficiently low viscosity and as a general rule of a PEG between 150 and 300; they have was able to obtain particularly satisfactory results when using a PEG 200.

The antipyretic composition according to the invention is characterized by its stability in aqueous solution in all concentration but also for its stability throughout the time and for the absence of degradation phenomena or of precipitation after prolonged storage.

To verify this last property, they have studied the variations of paracetamol concentration during a storage of 42 months both at room temperature and at a temperature of 37 ° C, in compositions according to the invention which originally contained a weight of 20% dissolved paracetamol in polyethylene glycol 200.

This test has been carried out in three batches of composition A, B and C.

The results obtained are reflected in the Tables attached.

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These tables are intended to prove that the paracetamol concentration of the composition according to the the present invention has not varied practically over time and It is equal to the initial value with a variation of + - 10%.

The present invention makes reference thereto mode, to a method of incorporating the composition antipyretic already mentioned to the animals drinking water in a hatchery equipped with a water circulation circuit that can be activated automatically thanks to some associated commands in particular to level probes or detectors of the presence of animals

According to the invention, the first stage of said procedure consists in determining a concentration of paracetamol water, taking into account the prescribed dosage, the animal development or growth tables, as well as those of water consumption, on average, of the animals to be treated.

Once the concentration of setpoint, the quantity should be added to the circulation circuit of concentrated paracetamol solution dissolved in a polyol of mentioned type that allows obtaining said concentration at the level of pipettes or rafts intended to quench the thirst of treated animals

According to a first form of execution of the invention, the water circulation circuit intended for breeding of cattle is connected to a large warehouse containing the amount of water needed for a group of animals for a certain time, particularly for a day.

According to this first variant of the invention, after determining the setpoint concentration For drinking water in paracetamol:

-

Be Calculate the amount of concentrated solution that should be added to the water contained in the tank to obtain a water containing said paracetamol concentration,

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Be enter this amount of concentrated solution in the tank, Y

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Be Stir the solution obtained by this procedure.

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According to a second variant of the invention, the water circulation circuit is connected to the network of water distribution

According to this second variant of the invention, we place on the water circulation circuit a adduction duct attached, on the one hand, to a cuvette intended for receive a stock solution with a 50% concentration in paracetamol and, on the other hand, connected to a dosing pump provided with a dispenser, and after having preset the concentration of drinking water in paracetamol:

-

we calculate what the concentration of the existing stock solution in the cuvette to obtain a water provided with said concentration taking into account the pump dispenser,

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we calculate how we should dilute the concentrated solution to obtain said stock solution,

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We prepare this stock solution with 50% paracetamol concentration by dissolving the solution concentrated and we introduce it inside the battery.

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This variation of the invention according to the which concentrated paracetamol solution dissolved in a low molecular weight polyethylene glycol undergoes two solutions successive results particularly advantageous.

In the picture, it should be well understood the It is imperative that the paracetamol-based formulation be perfectly soluble, in all dissolution states, for exclude any risk of obstruction of the circulation circuit of Water. It should be borne in mind that such obstruction could in particular occur at the level of the pump feed tube dosing that extends at the bottom of the stack containing the stock solution, at the level of the dosing pump and also at the level of the command instruments, allowing activation automatic circuit of water circulation and pipettes in the case that this solution is intended for birds.

In accordance with the present invention, the pump It has, as a general rule, a dispenser of an interval between a 1 and 5% and preferably, it must be a commercial pump in the that the dispenser is adjustable.

It should be noted that said pump Dosage can, after rinsing it, be used for introduce other products into the drinking water of animals active medications (antibiotics ...).

We have been able to establish that for the animals of a farm, the dosage that must be prescribed is, as a rule general 30 mg paracetamol per kilogram of live weight and day.

Taking into account the growth charts or animal development and water consumption, for example, of The animals to be treated. We have been able to determine that, on the one hand, in the case of meat chickens, the concentration of drinking water in paracetamol should be of the order of 75 to 225 milligrams per liter, to which corresponds, if a dosing pump has been used 2% with a stock solution containing 3.75 to 11.25 grams per liter of paracetamol and that, on the other hand, in the case of pigs, the concentration of water in paracetamol should be of the order of 300 and 500 milligrams per liter, which corresponds to whether used a 2% dosing pump with a stock solution containing between 15 and 25 grams per liter of paracetamol.

The use of a concentrated solution of paracetamol dissolved in a low molecular weight polyethylene glycol to 20% that clearly allows respecting the given data.

Indeed, in the case of a circuit of circulation attached to a tank with a capacity of 1000 liters, the added in said deposit of between 375 milliliters to 2.5 liters of concentrated solution, while that in the case of a circulation circuit connected to a network of water distribution and equipped with a 2% dosing pump, the addition of between 18.75 milliliters to 125 should be provided milliliters of concentrated solution per liter of solution mother.

These figures show that the antipyretic composition according to the invention is adapted perfectly to the use to which it is intended.

The present invention also makes reference to a method of incorporating the antipyretic composition mentioned above to feed the animals through their spray on granulated foods.

According to said procedure, the antipyretic composition on said foods at the end of their manufacturing process, with the help of a device spraying, more specifically by means of a hopper provided with spray ducts in which granulated foods fall by gravity to feed an evacuation device as per example a truck or conveyor belt.

It is essential not to spray the composition antipyretic on food until you have finished your manufacturing, so that said composition does not suffer the treatments thermal or mechanical to which granulated foods are subjected in the course of its manufacture.

This procedure presents, among others, the advantage that it allows a spray on an amount determined food granules, depending on the demand of the user and that allows you, for example, in a tow truck supply powdered food only to animals patients who are thus isolated.

According to another feature of this procedure, a consigned concentration of granulated foods in paracetamol, taking into account the dosage prescribed, the growth or development tables of animals, as well as the average consumption of food by the animals to be treated, determining the amount of antipyretic compound that should be pulverized depending on the amount of food to be treated, and specifically, measuring the demand for falling granulated foods inside the hopper, and programming, depending on it, the spray device

Claims (10)

1. Antipyretic composition for veterinary use suitable for the treatment of livestock animals intended for human consumption, in particular pigs, poultry and calves, characterized by containing a concentrated and stabilized solution intended, on the one hand, for incorporation into the water they drink or to be sprayed on the granulated foods, said solution contains, on the other hand, between 15 and 20% by weight and preferably 20% paracetamol (4-hydroxy-acetanilide) dissolved in a low weight polyethylene glycol compound molecular and / or polypropylene glycol. 2. Composition according to claim number 1, characterized in that it contains, in weighted proportions, between 40 and 85% polyethylene glycol and between 0 and 45% polypropylene glycol. 3. Composition as set forth in claims 1 and 2 characterized in that it contains 5% excipients, for example, appetite agents. 4. Composition according to claims 1 to 3, characterized in that it is composed of a PEG of 200.

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5. Method of incorporating the antipyretic composition into the water of watering animals, according to any one of claims 1 to 4, in a farm equipped with a water circulation circuit capable, of one part, of being activated automatically thanks to to some commands and on the other hand connected to a tank that contains a quantity of water necessary for a group of animals during a certain time, specifically during a day, characterized by the following steps:

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Determine a setpoint concentration of water in paracetamol, taking into account the prescribed dosage, the development or growth charts of animals, as well as the average water consumption of the animals to be treated.

-

Calculate the amount of solution concentrate that must be added to the water contained in the tank to obtain a water containing the concentration of slogan in paracetamol,

-

Introduction of that amount of solution concentrated in the reservoir and

-

Shake The solution obtained.

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6. Procedure for incorporating the antipyretic composition into water intended to water animals, in accordance with the provisions of any of claims 1 to 4, in a farm provided with a water circulation circuit capable of being automatically activated thanks to some control organs and, on the other hand, connected to the water distribution network, characterized by the following steps:

-

Hook on the circuit water circulation of a connected adduction duct, of a part, to a raft destined to receive a stock solution of paracetamol and, on the other hand, connected to a pump provided with a dispenser

-

Determination of a concentration of water setpoint in paracetamol, taking into account the dosage prescribed, the development or growth charts of animals, as well as the tables of average water consumption of animals to try.

-

Calculation of what the concentration of the paracetamol stock solution present in the raft to obtain a water containing the concentration recorded of paracetamol, taking into account the doser of the bomb.

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Calculation of how to dilute the concentrated solution to obtain said stock solution.

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Preparation of the stock solution with a 50% concentration of paracetamol, for the dissolution of concentrated and its introduction in the raft.

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7. Method according to claim 6, characterized in that the dosing pump has a dispenser between 1 and 5%. 8. The method as set forth in claims 6 and 7, characterized in that the dosing pump is a commercial pump in which the dispenser is adjustable. 9. Method of incorporating the antipyretic composition according to any one of claims 1 to 4, to feed the animals, spraying it on the granulated foods, characterized in that the antipyretic composition is sprayed on said foods at the end of its manufacturing process , in the same factory and with the help of a spraying device, essentially consisting of a hopper equipped with a spray duct inside which the granulated food falls by gravity, to feed an evacuation device such as a truck or a conveyor belt

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10. Method according to claim number 9, characterized by the following steps;

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Determination of a concentration of slogan of paracetamol granulated foods, taking into account the prescribed dosage, the development or growth tables of the animals, as well as the average food consumption by animals to be treated,

-

Determination of the amount of antipyretic composition that must be sprayed depending on the amount of food to be treated, specifically calculating the demand of granulated foods that fall inside the hopper, Y

-

Device Programming spray according to needs.