WO2014205531A1

WO2014205531A1 - Enriched feed for aquaculture

Info

Publication number: WO2014205531A1
Application number: PCT/BR2014/000175
Authority: WO
Inventors: Marili Villa Nova Rodrigues RODRIGUES; Renata Antunes Estaiano DE REZENDE; Felix Guillermo Reyes REYES; Rodney Alexandre Ferreira RODRIGUES
Original assignee: Universidade Estadual De Campinas - Unicamp
Priority date: 2013-06-27
Filing date: 2014-05-26
Publication date: 2014-12-31
Also published as: BR102013016609A2

Abstract

The present invention describes feed enriched with active substances and provided with a polymer coating for aquaculture, capable of reducing the leaching rate of the active principle in water. Besides being used to control diseases that affect animals in aquaculture, including fish, frog and crab farming, this feed can also be used in low concentrations as a prophylactic agent when handling these animals.

Description

Enriched Ration for Aquaculture

Field of the Invention

The present invention relates to an enriched feed for aquaculture. More specifically, the present invention is directed to a biologically active and polymer coated feed enriched feed to reduce the leaching rate of the active to water.

This ration can be used to control diseases that affect animals in aquaculture, including fish farming, ranching and shrimp farming and also be used in low concentrations as a prophylactic agent during the management of these animals.

Background of the Invention

Recent data from the Ministry of Fisheries and Aquaculture (MPA) show that fish farming is one of the fastest growing intensive farming systems in the world, reaching 142 and 146 million tonnes in 2008 and 2009, respectively. Brazil, which has great potential to meet the demand for aquaculture products, accounted for only 0.86% of world fish production in 2009, producing 1,240,813 tons during the whole of 2009, up four places compared to the previous year. the previous year (MPA, 2010).

In Brazil, there are several structures used in intensive aquaculture production systems. The main breeding structures used in fish farming, according to the National Aquaculture Census conducted during 2008, are the reservoirs, followed by the excavated ponds, net ponds (this one grew only in recent years), masonry tanks, boxes without water circulation, among others.

In intensive fish farming, the breeding of animals takes place from the possibility of creating in a small volume of water a high density of fish in confinement (kg fish / m ³ ). inevitably live in constant condition good management practices are necessary to avoid the appearance of infectious and / or parasitic outbreaks among animals.

To combat this stress imbalance, several strategies can be adopted, the most appropriate being those related to preventive management. Good management practices when used rationally within intensive aquaculture can lead to a decrease in mortality rates with consequent increase in productivity.

Infectious disease caused by bacteria and other pathogens is considered a serious problem in fish farming because it represents a potential risk in production, as they are usually present in environments and fish (Martins et al., 2000). These infections, when uncontrolled, have serious consequences, such as injuries that prevent their commercialization or high mortality causing great economic losses.

For proper treatment of bacteriosis, for example, prior knowledge of the causative agent of the disease in question is required. Often, to control a particular disease it is necessary to use antibiotics that, if misused, are not effective during treatment, can also cause damage such as increased bacterial resistance in these animals and production facilities where they are located, as well as higher waste rates in the environment. The presence of medicated residues, available both in fish and in the production environment, presents risks to human health due to their toxicity, as well as potential environmental impact and constitutes a barrier to export.

To treat a sick animal in aquaculture, it is necessary to administer the medicine to the entire population sharing the same environment. In this case, during therapy, the drug becomes available to animals that have difficulty feeding the feed for a certain period of time, thus determining a greater predisposition to strains of resistant microorganisms. Only the use of antibiotics is not sufficient and should be associated with good management practices (Klesius, 1995).

The vast majority of pharmaceutical products used in aquaculture are bioaccumulative and may persist in the environment for long periods after administration (Boyd & Queiroz, 2004). In the case of antibiotics, they can cause various toxic effects on target and non-target organisms due to the accumulation and persistence of these compounds influenced by physical chemical water (pH, temperature, salinity) or environmental (temperature and light) factors (Ferreira, 2007 ).

A large percentage of medicines administered to animals in the most diverse means of production reach the environment through the unconsumed medicated feed and, thus, the accumulation and persistence of these compounds in the environment. Hence the importance of leaching tests that serve to calculate the percentage rate of drug that was lost in the environment after its detachment in the feed.

Several documents related to the types of medicated feed are found in the literature and the most relevant are cited below.

Aquaflor®, a 50% premix with Florfenicol as its active ingredient, very commonly used in tilapia to combat haemorrhagic septicemia caused by mobile Aeromonas and Streptococcus caused by Streptococcus agalactiae, is incorporated with fish or vegetable oil in the proportion of 0.5 - 1.0% of the amount of feed to be offered to the fish. This mixture is added to the feed, thus producing medicated granules. However, the use of vegetable oil in medicated feed can cause severe liver damage to fish and water contamination. The present invention does not employ such material due to its hepatotoxic effect and also does not require extrusion of the active together with feed constituents to prevent possible thermal degradation.

In studies by Carrachi, 2010, oxytetracycline (OTC) medicated diets were used in ecotoxicity and efficacy trials. For each kilo of feed used in these trials, homogeneous, distinct amounts of OTC dissolved in 2% vegetable oil. Then the diet was kept at room temperature for four days, followed by biological assays without previous quantification of the drug in the diet.

Lipids are important and necessary elements in any animal's diet as they provide the body with the necessary energy. However, in high concentrations they can influence the good functioning of the animal organism (Ribeiro et al., 2008). Excess fatty acids administered to animals during treatment with medicated feeds can cause hepatic steatosis with reduction of the maximum speed of enzymatic reactions, as well as undesirable fat accumulation due to carcass lipid resynthesis, altering the chemical composition of the fillet.

Menotta, 2012, describes a premix for use in pig feed containing an antibiotic (amoxicillin) coated with hydrophobic material, used to improve the palatability of medicated feed. In the present invention, a hydrophilic coating is performed on the enriched feed as a whole, not in the microencapsulated form of the active ingredient, which has enabled the reduction of the active leach rate to the aquatic environment.

Alam, 2000, evaluates the necessary levels of amino acids in fish feed, especially methionine (limiting amino acid), aiming at weight gain for warm water fish. The authors cite a procedure using carboxymethyl cellulose (CMC) to prevent amino acid leaching into water, but the efficiency of this leaching coating technique is not demonstrated, it is only focused on fish weight gain from the feed produced. The advantage of the present invention is that the feed does not have to go through a pelletizing process and the feed employed is ready for consumption, with balanced nutritional characteristics including the ease of digestion of these components. In addition, the feed coating was developed in the presence of polymer and absence of oil, which ensures the homogeneity of the active dosage in all granules, as well as avoiding oil baths due to liver damage caused to fish. Langdon, 2003, discusses various formulations (lipid wall capsules, protein wall capsules, liposomes, lipid particles) for preparation of microparticulate feed for larval feed and nutrient leaching rate. Unlike the ration presented in the present

According to the invention, which is applied to fish feed, the formulations described are directed to larvae and therefore require a microparticulate feed, which facilitates the leaching of the compounds due to their larger surface area. For the production of these formulations it is necessary to use more elaborate techniques which increases the cost of the final product.

10 López-Alvarado, 1994, deals with the effect of coating and encapsulation of crystalline amino acids on the feeding of marine fish larvae and their leaching. Three types of microparticulate diets were evaluated in order to increase amino acid retention and the best results were obtained by encapsulating the amino acids with material.

L5 lipid, yielding a leach rate of 1.4% when the capsules were suspended for 2 min in 8.5 buffer. Unlike what was described by López-Alvarado, in the present invention the active ingredient is incorporated into a ready-made feed, which already has all the ideal dietary requirements for the fish. The incorporation of the asset is performed preserving the physical structure of the granule, the

10 nutritional balance in its composition and also ensuring the acceptability of this ration. Coating of the polymer enriched feed led to a loss of only 1.78% of the active when suspended in water at 22 ° C for 5 minutes. In the work cited in this document, because it is larval feeding, it is necessary to obtain microparticulate feed, where the use of

5 lipid walls proved to be promising. Since in the present invention, the particle size of the feed is very different because it is the feeding of fish and coating with hydrophilic polymer led to decreased leaching rate _^

Rigos, 1999, studies the rate of leaching antibiotics lo (oxytetracycline and oxolinic acid) by incorporating them into commercial feed and oil coating. Lower Leaching Rates were obtained with the incorporation of antibiotics in the diet, but what is striking is the short time spent on the medicated diet (1, 2 and 3 min). In addition to the inhomogeneity of the product when oil coating is employed, another major disadvantage is with regard to the hepatotoxicity problem that this oil may cause in fish, which is not found in the present invention.

WO2009023013 and WO2009023014 describe a composition comprising various granular cores containing the active ingredient and polymers for forming a hydrogel to mask the taste. Disadvantageously, none of them refer to the serious leaching problem, nor does it undertake studies to reduce it. In addition, the present invention promotes the incorporation of the active and the polymer into a balanced diet that will play a nutritional and medicinal role, given the difficulty in feeding and medicating via oral animals, bacterial diseases, or any other disease.

US2008031999 of 08/06/2007 describes a fish feed granule comprising an enzyme, copper ion and coating polymers, including PVP. However, two basic differences can be cited. The first difference refers to the absence of studies to verify leaching rates, which advantageously allows the control of drug loss in the production medium. The second and main difference is that the feed of the present invention is already pre-prepared, that is, of commercial origin, balanced according to the needs of each animal species.

Another document, US2008317825, deals with an oral pharmaceutical fish treatment composition which contains at least one pharmaceutical agent, a base additive and a support (polymer), and is intended to disintegrate at least partially into a acid environment. The main difference is that in the present feed the active is homogeneously incorporated directly into the animal feed, that is, when feeding the fish will be medicated in the correct dosage, concomitantly. The coating gastro-resistant has the function of preventing the gastric degradation of the active in order to improve its bioavailability. Therefore, the purpose of this coating differs completely in that it aims at better absorption of the drug into the fish organism and in our work the coating has the role of reducing leaching to the aquatic environment.

US7556802 describes a polymer coated feed (PVP) that contains an enzyme. In the present invention there is no need for high temperatures during feed preparation, which is also suitable for incorporation of thermolabile molecules. Additionally, because of their quick and easy preparation, cross-contamination rates during coating preparation and incorporation of the drug into feed are reduced.

WO2004039172 of 10/31/2002 presents results of the trout feed leaching study which requires a low water temperature. In this study, the water temperature was 15 ° C, which resulted in losses of less than 2% even after 60 min of exposure to water. In this invention it has been found that water temperature and feed time in the aquatic environment contribute significantly to the leaching of compounds, that is, the higher the temperature and / or the longer the leaching. The document cited indicates a wide range of solvents to be employed in the process, including chlorinated solvents, setting the boiling point limitation of the solvent to be below 120 ° C to facilitate evaporation, but no consideration has been given to toxicity. these solvents that even after evaporation may remain at residual levels in the fish. In addition, to reduce asset leaching, the inventors suggest the use of lipophilic agents. Already the present invention efficiently employs polymers which despite their water solubility can efficiently reduce the leaching of the tested asset.

In view of the foregoing, the present invention has advantages in several respects. Firstly, it proposes a new feed enriched with biologically active substance and an appropriate polymeric coating. THE The present invention advantageously employs a polymeric coating which provides for reducing the leaching rate of the active to the aquatic environment. In addition, this coating developed in the presence of polymer eliminates the presence of oil in the composition, ensuring the homogeneity of the active dosage in all granules, as well as avoiding the use of oil baths that have hepatotoxic action to fish. This feed also has ease of processing, without the need for sophisticated equipment and without the use of high temperatures, and can be used for thermolabile assets. Another crucial point is the guarantee of permanence of the buoyancy characteristics and nutritional value of the feed.

Among the various applications presented by this new feed, its use is highlighted in the control of diseases that affect animals in aquaculture, including fish farming, ranching and shrimp farming, and also, in low concentrations, as a prophylactic agent during the management of these animals.

Brief Description of the Invention

The present invention relates to an enriched feed comprising a nutritional carrier or nutritionally balanced carrier for the various aquatic species, biologically active substance and coating polymer.

The nutritional carrier can be selected from the group of pellets, extruded and pelleted granules and other forms of dry food, with different diameters according to the requirements of the species in question. Antibiotic, immunostimulant and antiparasitic classes may be employed as the biologically active feed substance of the present invention and the dosage value may vary according to the molecule, species and disease. The third major component is the coating polymer which can be selected from the polymers formed by multiple vinylpyrrolidone chains, preferably PVP-K30.

Another object of protection of the present invention is an enriched feed composed of an extruded nutritional carrier having 28% crude protein and diameter ranging from 4 to 6 mm; 1.2 g of enrofloxacin per kg of feed and polyvinylpyrrolidone as a coating polymer, ranging from 0.5 to 2.0%.

It is an additional object to use this food in the control of diseases that affect animals in aquaculture, including fish farming, ranching and shrimp farming and also, in low concentrations, as a prophylactic agent during the management of these animals.

Brief Description of the Figures

The structure of the present invention along with additional advantages thereof can be better understood by reference to the appendices and the following description:

Figure 1 shows the chromatograms obtained by HPLC at 280 nm from (A) white feed and (B) enriched feed.

- Figure 2 shows the analytical curve of enrofloxacin. - Figure 3 shows in graph form the enrofloxacin leaching rate (ENR) contained in the diet with and without the addition of PVP under experimental design conditions.

Detailed Description of the Invention

The present invention discloses a stable biologically active and polymer coated feed intended for aquaculture capable of reducing leaching rates to the aquatic environment, ensuring homogeneity of dosage of the administered active ingredient.

The feed of the present invention comprises the following major components: nutritional carrier, biologically active substance and coating polymer.

Carrier is a nutritionally balanced and formulated food for various aquatic species that can be selected from the group of pellets, extruded and pelletized granules and other forms of dry food according to the requirements of the species concerned. Carriers may have different diameters and protein percentage, according to the species and growth phase of the animal that will make use of this protein. product. The diameter is closely related to the coating and can range from 1.7mm for Aievins, up to 2-4mm, 4-6mm, 6-8mm, 8-10mm and 14-20mm for the final stages of growth and termination. fish farmed in excavated ponds.

The biologically active substance employed, both synthetic and natural, can be selected from the classes of antibiotics, immunostimulants, antiparasitics and their associations allowed in aquaculture. Among the antibiotics that can be used are the class of macrolides (erythromycin, josamycin, spiramycin, neoespiramycin, josamycin, tilmicosin), quinolones (sarafloxacin, enrofloxacin, norfloxacin, ofloxacin, difloxacin, tetrolinoxin, oxyquinoline, oxyquinoline) oxytetracycline, tetracycline and chlortetracycline), amphenicols (florfenicol, chloramphenicol, thiamphenicol), sulfonamides (sulfathiazole, sulfamethazine and sulfadimethoxine), pyrimidines (trimetropin) and their combinations. Antiparasitics may include the phosphorus class (trichlorphon), Levaisol and their associations. Immunostimulants include the glycan class (beta glucan), the vitamins (C and E), the polysaccharides (mananoligosaccharides, zimozana, scleroglucana), and Levaisol. The dosage value applied varies according to the molecule, species and disease being treated.

The third main component is the coating polymer that can be selected from those that promote the reduction of the leaching rate of the formulation ingredients, both the active ingredient and the other constituents, avoiding environmental and health damages. Due to all the characteristics mentioned above, the polymers formed by chains of multiple vinylpyrrolidones are excellent materials of choice for coating formation, mainly PVP-K30. In addition to these components, the feed of the present invention may further comprise optional components to provide some desirable feature not achieved with the aforementioned components. Some of these compounds that can be added are as follows: natural scents and essences and synthetic oils in order to increase the palatability of the product, such as the essence of corn.

Example 1: Feed Production

In the coating process a bench mixer was used, simple equipment, low cost and easy operation, making accessible the process of obtaining medicated feed in the aquaculture production system.

The operating conditions, ie mixer speed, spray time and granule drying temperature, were optimized to obtain a homogeneous and stable material. Thus, the rotation of the equipment should be sufficient to allow the entire surface of the feed to be wettable without breaking the material. The spray time should allow homogeneous humidification of the granules, with the coating solution avoiding excess and consequent accumulation of liquids in the equipment. The drying temperature should be mild to allow evaporation of the hydroalcoholic solution without degrading the active should be applied concurrently with the spraying step.

In view of the above, it was established a time of 2 min for spraying, equipment rotation of 80 rpm and a maximum drying temperature of 50 ° C for 10 min.

An initial batch of medicated feed containing 0.5% and 2.0% PVP was produced using optimized process conditions. Material containing 0.5% PVP was also employed in the development and analytical validation stage.

Example 2: Determination of enrofloxacin

Analytical System Compliance

Determination of enrofloxacin content in the medicated feed was performed by high performance liquid chromatography coupled to the diode array detector (HPLC-DAD). The chromatographic separation was performed on an analytical RP18 column monolithic 100 x 3 mm (Merck® Darmstadt, Germany) operating at 40 ^Q C using as eluent a mixture of 0.1% formic acid and acetonitrile in the ratio 92: 8 (v / v) at 1.5 mL min ^"1. The injection volume was 20 μΐ_ and detection at 280 nm.

Sample Preparation

1.0 g of the feed, equivalent to 15 pellets, initially extracted with 10.0 mL of a mixture containing 1% formic acid solution and 70:30 v / v acetonitrile (extracting solution) in a 20 µm falcon tube, was used. .0 mL. Pellet disruption and homogenization was achieved by using the ultraturrax disperser for 1 min, after which the sample was placed in an ultrasound bath for 5 min. Sequentially, the sample was centrifuged at 2800 g for 5 min. To ensure exhaustive sample extraction, this procedure was repeated for one more time and the supernatants pooled in a 25 mL volumetric flask, completing the volume with the extraction solution. This solution was diluted 1: 10 v / v in Milli Q water, and filtered through a 0.22 μιη membrane before injection into the liquid chromatograph.

Validation of the analytical method

The analytical method developed for the determination of ENR in medicated feed was validated following the recommendations of the Guide for Validation of Analytical and Bioanalytical Methods (ANVISA, 2003) and the Guide for Validation of Analytical Procedures and Quality Control - Veterinary Medicines, Pharmaceuticals, Pharmaceuticals and other Substances in Animal Feed Products and Breeds of Biological Origin (MAPA, 2010).

The parameters evaluated were: selectivity, linearity, linear range, precision (intra-run and inter-run) and accuracy.

The selectivity of the method was confirmed by the absence of interfering peak in the white diet (n = 10) in the retention time of the ENR. Figure 1 shows the blank chromatograms and sample containing ENR. The linearity of the method was evaluated by calculating the correlation coefficient (r) of the analytical curve constructed with 6 concentration points, in the range of 1, 13 and 1 1, 29 ml_ ^"1 (Figure 2). The value obtained was r = 0.9997, which meets the minimum acceptable criterion recommended by ANVISA (r = 0.99).

The accuracy of the method represents the dispersion of results between independent and repeated assays of the same sample and was evaluated under repeatability conditions, ie, same-day analysis by the same analyst and same equipment (untrained precision) and reproducibility, or that is, analysis performed on 3 consecutive days by the same analyst and same equipment (precision incurred). Precision results were expressed as the coefficient of variation (CV,%) of the results obtained with 7 replicates using the medicated feed. The ANVISA Validation Guide (2003) recommends that under intra and uneventful accuracy conditions the CV value should not exceed 5.0%.

The result obtained in the determination of the intra-race precision presented coefficient of variation (CV) of 2.98% and the inter-race precision, evaluated in three consecutive days, presented CV of 2.26%, which meet the Validation Guide from ANVISA (2003) r

The accuracy of the method was assessed by the recovery test using ENR-fortified diets at 3 concentration levels corresponding to 50, 100 and 150% of the expected value, which corresponded to concentrations of 600, 1200 and 1800 mg kg ^"1. The results were expressed as the recovery percentage using the following equation:

~ ~ ENR.

% recovery = -

ENR_

Where,

ENR _enc = concentration of ENR determined in fortified feed (μς g ^"1 ); ENR _adá = concentration of ENR added in white ration, ie fortification of ration expressed in μς g ^"1 ;

The results obtained for the three concentration levels were 98.8%, 101.1% and 102.4% recovery, respectively. It should be mentioned that the ANVISA Guide does not recommend recovery percentage values. However, the results obtained are within the acceptance range recommended by the MAPA Validation Guide (2010), which is 97 to 103% for analytes at concentrations of 1000 μ9 g ^{~ 1} .

Table 1 presents the results obtained in the validation of the analytical method.

Table 1: Validation results of the developed analytical method

Parameters Enrofloxacin

Linearity (r) 0.9997

Example 3: Experiment Lane

From the choice of PVP as a coating polymer, a 2 ^4'1 fractional experimental design was carried out to evaluate the most important variables in the leaching test. The variables with the respective studied ranges selected for the study were: pH (7.0 and 7.8), water temperature (22 and 28 ° C), ration time in water (5 and 30 min) and polymer concentration (0.5 and 2.0%). The response evaluated in the experimental design was the percentage of drug leaching, calculated according to the equation below:

„. ,. . . ~ (initial content-final content) „.-. ,,

% leaching = 7— x

initial content 100,

Where the initial and final levels of feed active (dry basis) were determined by the validated analytical method. Table 2 shows the experimental conditions of the tests performed.

Table 2. Experimental conditions of the fractional experimental design test 2 ^{4 "1} .

PVP = polyvinylpyrrolidone.

The ENR content of medicated diets used in experimental design assays, coated with solutions containing 0, 0.5 and 2.0% PVP, were initially quantified by HPLC. Results are presented in Table 3.

Table 3. Enrofloxacin (ENR) content in medicated feeds used in experimental design trials prior to exposure to water.

Coating Moisture ³ Medium content ENR CV ^C

PVP (%) (%, m / m) (%, m / m) ^b (%)

0 12.66 0.097 (n = 3) 1, 3

0.5 13.30 0.1 15 (n = 8) 4.3

2.0 12.89 0.109 (n = 8) 4.4 a. . . ·. B .

the one determined in triplicate; dry base content; ⁰ CV = coefficient of variation.

From the results presented in Table 3, there is a low dispersion of the results (CV less than 4.5%) related to the ENR content in the feeds, thus showing a good uniformity in the process. sprinkling of ENR during the preparation of medicated feed. That is, obtaining a homogeneous feed as to the content of ENR.

Then, the leaching test was performed according to the tests proposed in the experimental design (Table 2). Table 4 presents the results obtained.

Table 4. Responses from fractional experimental design 2 ^{4 "1} .

01 28 2.0 30 7.8 29.97

02 28 2.0 5 7.0 26.71

03 28 0.5 30 7.0 32.52

04 28 0.5 5 7.8 20.16

05 22 2.0 30 7.0 28.42

06 22 2.0 5 7.8 1.78

07 22 0.5 30 7.8 20.58

08 22 0.5 5 7.0 7.95

1 .. .

PVP = polyvinylpyrrolidone.

The responses obtained in the experimental design tests were processed using Statistica software, version 5.0, to determine the effects of the variables.

Table 5 presents the results of the effects of the variables on the leaching rate.

Table 5. Effect of the studied variables in fractional planning on the enrofloxacin leaching rate present in the diet.

Effects Variables (% leaching)

Temperature (° C) 12.66 ^*

PVP ¹ (%) 1, 42

pH -5.78

Time (min) 13.72 ^*

PVP = polyvinylpyrrolidone; ( ^* ) Statistically significant (p <0.05). According to the data in Table 5, the statistically important variables were the temperature and the time spent in the water, both with positive effects in the same order of magnitude. This means that an increase in water temperature from 22 to 28 ° C promotes an increase in leaching rate of 12.66%. For the time spent in the water, an increase from 5 to 30 min promotes an increase in the leaching rate of 13.72 o // o.

Since when used in the coating solution in the 0.5 to 2.0% concentration range, PVP had no significant effect on the feed to water ENR leaching rate, it was decided to repeat the experimental design conditions. without the presence of the polymer in order to verify its efficiency in reducing the leaching rate. Figure 3 presents the results obtained in the ENR leaching rate of the diet with and without PVP coating, using a solution containing 0.5% of the polymer.

It was verified that under all experimental conditions (temperature, time and pH) there was a reduction of the ENR leaching rate when PVP was coated. The best results in reducing the leaching rate were under test conditions 6 (2.0% PVP) and 8 (0.5% PVP), which were performed under conditions of 22 ° C and 5 min residence time. feed in water. Data indicate that a 0.5% PVP coating solution was sufficient to minimize ENR leaching.

Claims

1 . Enriched feed comprising the following main components: nutritional carrier, biologically active substance and coating polymer.

Feed according to Claim 1, characterized in that the carrier is a formulated and nutritionally balanced food for the various aquatic species selected from the group of pellets, extruded and pelleted granules and other forms of dry food, according to the requirements of the species concerned.

Feed according to claim 2, characterized in that the carrier has different diameters, according to the species and growth phase of the animal that will make use of the feed.

Feed according to Claim 3, characterized in that the diameter of the carrier can range from 1.7mm for fingerlings to 2-4mm, 4-6mm, 6-8mm, 8-10mm and 14-20. mm for the final stages of growth and termination of fish farmed in excavated ponds.

Feed according to claim 1, characterized in that the biologically active substance is selected from the classes of antibiotics, antiparasitics and immunostimulants.

Feed according to claim 5, characterized in that the antibiotic is selected from the class of macrolides (erythromycin, josamycin, spiramycin, neoespiramycin, josamycin, tilmicosin), quinolones (sarafloxacin, enrofloxacin, norfloxacin, ofloxacin, danfloxacin, difloxacin, oxolinic acid and flumequine), tetracyclines (oxytetracycline, tetracycline and chlortetracycline), amphenicols (florfenicol, chloramphenicol, thiamphenicol) of sulfonamides (sulfathiazole, sulfamethazine and sulfadimethoxine), pyrimidines (and their combinations).

Feed according to claim 5, characterized in that the antiparasitic to be selected from the phosphorus class, preferably trichlorphon, Levaisol and their combinations.

Feed according to Claim 5, characterized in that the immunostimulant is selected from the class of glycans (beta glucan), the polysaccharides (mananoligosaccharides, zimozana, scleroglucan), Levaisol, vitamins (C and E), Levaisol and their associations.

Feed according to claim 5, characterized in that the dosage value of the biologically active substance varies according to the molecule, species and disease.

Feed according to claim 1, characterized in that the coating polymer is selected from the polymers formed by multiple vinylpyrrolidone chains, preferably PVP-K30.

1 1. Feed according to claim 1, characterized in that it comprises optional components selected from natural and synthetic flavors and essences, preferably corn essence.

12. Enriched feed comprising an extruded nutritional carrier with 28% crude protein and diameter ranging from 4 to 6 mm; 1.2 g of enrofloxacin per kg of feed and a range of 0.5% to 2.0% polyvinylpyrrolidone.

Feed according to claim 12, characterized in that it has a leaching rate of 1.78% for feeds coated with 2.0% PVP and 7.95% leaching for feeds coated with 0.5% PVP. .

Use of the feed described in claims 1 to 13 for use in the control of diseases affecting animals in aquaculture, including fish farming, ranching and shrimp farming.

Use of the feed described in claims 1 to 13 characterized in that it is used at low concentrations as a prophylactic agent during the handling of animals in aquaculture, including fish farming, ranching and shrimp farming.