HRP930083A2 - Veterinary-medical preparation, used as an additive to drinking water or to the animal food, containing the antibiotic mixture of gentamicin and lincomycin; its use in pig-breeding - Google Patents

Description

The technical field to which the invention belongs

The subject of the invention belongs to the field of veterinary medicine, and especially to the field of animal nutrition.

According to the International Classification of Objects (ICC), the subject of the invention is classified, i.e. classified and marked with the symbol A23K 1/17, which defines animal feed with antibiotics.

This invention is a supplementary invention to the Slovenian application P-9200002 and relates to a veterinary medicinal preparation as an additive to drinking water or animal feed, which contains an antibiotic mixture of gentamicin and lincomycin, which can be in the form of free bases or acid addition salts, as gentamicin sulfate and lincomycin hydrochloride, as well as for use for the purpose of prophylaxis, and treatment of dysentery and colibacillosis and prophylaxis of enzootic pneumonia of pigs, and individually for increasing their body weight gain, reducing losses and reducing the number of decrepit animals.

Technical problem

In intensive pig farming, the greatest losses in weanling pigs are caused by gastrointestinal and pneumonic diseases, and for this reason there is a constant need for effective prophylaxis and therapy of these infections with effective antibiotics, or combinations of antibiotics, as an addition to drinking water or animal feed , which would consequently increase the increase in body weight and reduce the deaths of piglets.

State of the art

The use of various antibiotics and combinations of antibiotics, which are added to animal feed or drinking water, is known from the literature to prevent and treat infections in animals for fattening, and at the same time they have an effect on body weight gain. Lincomycin is a known antibiotic, which was described in US patent no. 3086912, which inhibits the growth and reproduction of numerous microorganisms, especially gram-positive bacteria, such as species of staphylococus, Streptococus, Clostridium, Bacillus anthracis and Corynebacterium and some gram-negative bacteria, such as Bordetella and Haemophilus, and some species of Nocardia and Actinomyces. It is particularly effective against Treponemo hyodysenteriae, Mycoplasmo hyopneumoniae and Mycoplasmo galliseticum. It has a bacteriostatic effect on sensitive microorganisms, and at higher concentrations (2 to 3 times higher MIC) it is also bactericidal.

In US patent no. 3 155 580 described galenic forms based on lincomycin, i.e. its acid addition salts, as an active ingredient for the treatment of infections caused by bacteria, in humans and animals. In fattening animals, the antibiotic can be used prophylactically, i.e. to increase body weight.

From US patent no. 3 150 042 the use of lincomycin for the prophylactic and therapeutic treatment of coccidiosis in animals is known, where it is used as an addition to ordinary animal feed or an adequate amount of drinking water. The use of tablets and sterile injection solutions is also described.

Gentamicin is an antibiotic, which was described in US patent no. 3 091 572 and US patent no. 3 136 704 and consists of three structurally related components, gentamicin C1, C2 and C1a. Gentamicin A is also known, which is structurally different from the other components of the complex. In galenic forms, gentamicin appears in the C complex sulfate form (gentamicin sulfate). Gentamicin is a very effective antibiotic against gram-positive and gram-negative microorganisms, such as staphylococcus, pneumomonas and proteus species, and is used both in human medicine and in veterinary medicine.

Spectinomycin is an antibiotic isolated from the fermentation broth of Streptomyces spectabilis and was described in US patent no. 3 234 094. Spectinomycin is active against mycoplasmo, some gram-positive and most gram-negative bacteria, and is used in veterinary medicine. In US patent no. No. 3,245,797 describes an animal feed containing spectinomycin in an amount effective to promote growth in fattening animals.

In US patent no. 3 261 687 describes an animal feed containing a combination of the antibiotic spectinomycin (in the form of a sulfate salt) and lincomycin (in the form of a hydrochloride salt) and a procedure for increasing body weight gain in fattening animals, where the ratio of the antibiotic is from 1 to 10 parts by mass of spectinomycin and 1 the mass fraction of lincomycin, in the composition of animal feed or in drinking water. They state that with this combination of antibiotics in animal feed or drinking water, they achieved unexpectedly good results in increasing body weight gain and the speed with which it grew. At the same time, the combination of both antibiotics in animal feed acts synergistically, and is also applicable for therapeutic and prophylactic treatment of infections in fattened animals.

Furthermore, from US patent no. 3,679,787 known combination of lincomycin and spectinomycin in a dosage unit, in combination with carriers, and is suitable for the treatment of animal diseases, due to their synergistic activity against microplasma infection.

Tiamulin is a semi-synthetic broad-spectrum, antimicrobial antibiotic, which was described in US patent no. 3 919 290 and acts especially on microplasmas, as well as on many gram-positive and gram-negative bacteria. In veterinary medicine, it is used in the prophylaxis and therapy of bloody diarrhea, as well as enzootic pneumonia in pigs, as well as other infections caused by microorganisms sensitive to tiamulin (in the form of respiratory diseases of animals, caused by microorganisms and secondary infections.

Description of the solution to the technical problem with examples

The invention is based on the task of finding a more effective combination of antibiotics in the composition of a veterinary medicinal preparation as an additive to drinking water or animal feed, for use in the prophylaxis and therapy of dysentery and colibacillosis and the prophylaxis of enzootic pneumonia in pigs, and consequently for increasing their body weight gain, reducing losses, as well as to reduce the number of dilapidated piglets and their mortality rate. The results that would be obtained with such a combination of antibiotics in the composition of a veterinary medicine, as an addition to drinking water or animal feed for pigs, would surpass the action of individual antibiotics or known combinations of antibiotics for the same purposes, which would represent a valuable improvement in pig farming.

In the Slovenian patent application P9200002, we described an animal feed and addition to it or to drinking water for poultry farming, which contained an antibiotic mixture of 1 part by mass of gentamicin sulfate and 5 to 60 parts by mass of lincomycin hydrochloride for the prophylaxis and treatment of infections and consequently for increasing their body weight gain , where we increased the success factor to low food conversion and reduced total deaths.

In intensive pig production, gastrointestinal and pneumonic diseases cause the greatest losses in weanling pigs, that is, after the cessation of suckling for about three weeks. Among the causative agents of gastrointestinal diseases, the primary place is occupied by E.coli, which causes disturbances in the intestinal tract of newborn piglets, as well as in old age, especially after weaning. E.coli is a natural inhabitant of the digestive tract, as a co-profit with many other bacteria, where under changed conditions in the body, some compounds of E.coli cause disease.

Pathological conditions in animals are caused only by E.coli variants, which are capable of producing enterotoxins. By the term piglet coli infection, we mean a complex gastrointestinal disease with a diarrheic meaning. We distinguish between three forms of the disease, which are related to the age of the piglets, namely colidiarrhea of newborns from the seventh day of age, colibacillosis of piglets that are still suckling (10 days of age), and coligastroenteritis and colienterotoxemia from the teat of distant piglets.

Another disease, which causes significant direct and indirect losses in intensive pig farming (deaths or deaths due to decrepitude of pigs as a result of the disease) is enzootic (microplasmotic) pneumonia. The primary causative agent of this disease is Mycoplasma hyopneummoniea. In deteriorated microclimatic conditions with the cooperation of some bacteria, it causes a chronic disease with high morbidity (sickness) and low lethality (death). In piglets aged 3 to 8 weeks, the disease starts acutely, and in poor microclimatic conditions, the lethality can be higher than 10%. Deaths occur mainly due to secondary bacterial infections. Pigs affected by enzootic pneumonia have lower growth and lower conversion.

In our research on the possibilities of preventing coliinfections and enzootic pneumonia from the teats of distant piglets, we were surprised to find that by adding a new preparation to the drinking water or usual feed for pigs, in terms of the invention, we achieve the desired purpose, which in terms of prophylactic and therapeutic properties surpasses in the effectiveness of known commercial preparations for the same purpose.

The preparation according to the invention contains lincomycin and gentamicin, it can be in the form of free bases, but better in the form of their pharmaceutically acceptable acid addition salts, such as lincomycin hydrochloride and gentamicin sulfate, in parts by weight of 1:1 to 1:10, in addition to the usual water-soluble base. We achieved the best results with mass ratios of lincocin hydrochloride and gentamicin sulfate from 1:1 to 1:3. The preparation according to the invention can be administered in drinking water or in animal feed. The preparation is given to piglets from the first day of weaning. We examined the preparation in terms of the invention by comparing it clinically in pigs with respect to the commercial preparation Linco-Spectin 44 premix, which contains equal parts of lincomycin hydrochloride and spectinomycin sulfate, and the commercial preparation Tiavet P 2% powder, which contains tiamulin hydrogen fumarate, and can be given in the drink. water or feed for pigs in accordance with the manufacturer's recommendations.

The obtained results of the comparative clinical experiments on pigs showed, which is also shown in example 1, that with the application of the preparations according to the invention, compared to commercial preparations, total losses and deaths with symptoms of diarrhea and pneumonia during breeding are reduced. the percentage of decrepit among which there was no death at all, in addition, the conversion (use of food) is the lowest with the use of the preparation in terms of the invention, as a result, the daily increase in body weight also improves.

Based on the obtained results, we can use the preparation in terms of the invention for the prophylaxis and therapy of dysentery and colibacillosis, as well as for the prophylaxis of enzootic pneumonia in pigs and individually for increasing their body weight.

The combination of both antibiotics in terms of the invention is added to drinking water in a concentration of 1 mg/ml to 200 mg/ml of drinking water, however, the best results are obtained in a concentration of both antibiotics of about 50 mg/ml of drinking water.

We add the combination of both antibiotics as a supplement to animal feed for pigs in a total concentration of 0.5 kg/t to 5 kg/t, preferably around 1.5 kg/t of solid feed.

The invention is explained, but not limited, by the following two examples:

Example 1

Comparing the clinical trial of the antibiotic combination of the invention (lincomycin-gentamicin), the combination of lincomycin-spectinomycin and tiamulin in pigs.

We carried out comparative testing of the mentioned antibiotics, that is, the combination of antibiotics with which we wanted to clinically test the effectiveness of the combination of antibiotics in the sense of the invention, to prevent colibacillosis and enzootic pneumonia of pigs and, consequently, determine the increase in body weight.

We prepared the combination of antibiotics in terms of the invention in the form of a powder preparation, which has the following ingredients:

lincomycin hydrochloride 1.5 g

gentamicin sulfate 4.0 g

polyethylene glycol 4000 powder 2.0 g

lactose 42.5 g

50.0 g

The preparation is prepared by mixing fine-grained hard ingredients in a mixer, which can then be added to drinking water or animal feed.

We applied the antibiotic combination lincomycin-spectinomycin in the form of the commercial preparation Linco-Spectin R44 premix (Upjohn Comp. USA), which contains lincomycin hydrochloride and spectinomycin sulfate in a ratio of 1:1, while we applied tiamulin in the form of the commercial preparation Tiavet P 2% powder ( company Plica HR), which contains tiamulin hydrogen fumarate.

In the clinical trial of the preparation in terms of the invention, we included three groups from the teats of remote piglets:

- a group of 1620 weaned piglets received the preparation according to the invention

- a group of 1687 weaned piglets received the preparation Linco-Spectin 44 premix

- a group of 1602 weaned piglets received the preparation Piavet P 2% powder

The piglets of all three groups were of the same genetic origin.

The preparation according to the invention was applied in drinking water at a dose of 50 g per 100 liters from the first to 21 days after weaning. We did not notice any side effects in the animals that received the preparation according to the invention in their drinking water.

Before moving in the experimental animals, we washed the object with hot water under pressure, and disinfected it with the preparation VirkonR (Krka, SLO), which is a balanced and stabilized mixture of peroxide compounds, surfactants, organic acids and an organic buffer system.

The main ingredient is potassium peroxysulfate (50%). Immediately after moving in, the piglets received the vitamin preparation BCK-forte+E powder (Alkaloid, Skopje) in their drinking water, which contains vitamins A, B, E, C, B1, B2, B6 and B12 in a dose of 200 g per 100 liters of water in 2 days.

From the first to 21 days after weaning, the piglets received the preparation according to the invention in their drinking water at a dose of 50 g per 100 liters of water.

In the piglets being tested, we monitored daily occurrences of diarrhea and pneumonia as well as deaths. We weighed the piglets when they were removed from the teat and when they moved into the feedlot (tables 2 and 3).

The results of the tests after using the preparations according to the invention are shown in tables 2, 3, 4 and 5.

During the clinical testing of the preparation in terms of the invention, we separated 26 piglets (1.6%) that were lagging behind in body weight gain, into two separate pens. None of the mentioned piglets died until they were moved to the feedlot.

During breeding, 3.45% of piglets with signs of diarrhea and 1.3% of piglets with signs of pneumonia died (table 3).

Comparative examination

We tested two groups of pigs of the same age in the same barns.

Before the pigs moved in, we washed the facilities with hot water and disinfected them with VirkonR (Krka, SLO).

In the first experimental group, there were 1,687 weaned piglets that received the product Linco-Spectin 44 in the feed in accordance with the manufacturer's instructions, at a dose of 1 kg per ton of feed for 3 weeks. Piglets started receiving the drug 8 days after weaning.

The second comparison group consisted of 1,602 piglets removed from the teat, and received the preparation Tiavet P 2% powder in the feed in accordance with the manufacturer's instructions, at a dose of 1.25 g per ton of feed in 21 days (table 1). Also, this group started receiving the preparation from the 8th day of weaning.

Piglets in comparative testing were given the vitamin preparation BCK-forte+E in drinking water for 2 days in addition to the antibiotics mentioned in the feed, at a dose of 200 g per 100 liters of water.

In the animals in the comparative testing, we monitored daily occurrences of diarrhea and pneumonia as well as deaths.

We weighed the piglets when they were removed from the teat and when they were moved to the feedlot (tables 2 and 3).

During the clinical testing in the group receiving Linco-Spectin 44 we separated 89 decrepit piglets (5.28%), in the group receiving Tiavet P 2% we separated 112 piglets, which lagged behind in body weight gain (6.9 %). Of these, 27 piglets (30.3%) died in the first group, and 38 piglets (33.9%) in the second group.

Table 1.: Number of animals according to groups, product and dosage

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Table 2: Average body weight of piglets when weaned and moved to the feedlot and average daily weight gain

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Table 2 shows that the group of piglets, which received the preparation according to the invention in their drinking water, achieved the highest average body weight and the highest daily growth when moving to the feedlot.

Table 3: Total losses and deaths with signs of diarrhea or pneumonia and feed conversion during rearing

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Table 3 shows that in the group that received the preparation according to the invention, the total losses and deaths with signs of diarrhea and pneumonia during cultivation were the lowest in comparison with the groups in comparative testing.

Conversion is the lowest in the group that received the preparation according to the invention.

Table 4: Number of dilapidated piglets and proportion of deaths from them

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Table 4 shows that the lowest percentage of decrepit piglets was in the group that received the preparation according to the invention and that none of the decrepit pigs died in that group, and more than 30% in the comparison group.

Table 5 shows the overall results in all groups, which received the preparation according to the invention, Linco-Spectin 44 premix and Tiavet P 2%.

Summary of the results of clinical testing of the preparation in terms of the invention:

Clinical testing of the preparation according to the invention in weaned piglets showed that the preparation has no side effects.

The group of udders of remote piglets, which received the preparation according to the invention, showed improved results compared to the comparison groups, which received the commercial preparations Linco-Specti 44 premix and Tiavet P 2% in terms of:

- average daily growth

- average utilization of food

- percentage of total losses

- percentage of those who died with signs of pneumonia

- percentage of deaths with signs of diarrhea

- percentage of dilapidated

- the percentage of deaths of the decrepit.

Table 5:

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Example 2

The percentage composition of animal feed for pigs to which we give the combination of antibiotics in terms of the invention can be composed of the following ingredients:

Pre-start:

corn 40.23%

barley 10.00%

Wheat flour for feed 5.00%

soy trope 16.20%

Prelac Nutrifit F 2 EDR (milk supplement) 20.00%

fish meal 2.00%

sugar 3.00%

limestone 1.05%

ZoofosR (Ca, P) 0.32%

premix SP (vit.miner.) 1.00%

methionine 0.03%

Beginning:

corn 43.19%

barley 15.00%

Wheat flour for feed 5.00%

soy trope 16.18%

Prelac Nutrifit F 2 ED 15.00%

fish meal 2.00%

limestone 0.93%

ZoofosR 1.33%

premix SP 1.00%

animal salt 0.35%

Lysine 0.02%

methionine 0.01%

Grower:

corn 48.53%

barley 10.00%

wheat 10.00%

soy trope 21.15%

Prelac Nutrifit F 2 ED 4.00%

fish meal 3.00%

limestone 0.79%

Zoofos 1.20%

animal salt 0.42%

Premix SP 0.80%

lysine 0.09%

methionine 0.02%

Pre-start: 8 - 26 days of age

Start: 26 - 47 days of age

Grower: 47 – 80 days of age__

Claims (5)

1. Veterinary medicinal preparation as an addition to drinking water or animal feed for pigs, indicated by the fact that it contains an antibiotic mixture of 1 mass part of lincomycin and 1 to 10 mass parts of gentamicin or their pharmaceutically acceptable acid addition salts and a water-soluble carrier, for use in prophylaxis and therapy dysentery and colibacillosis and prophylaxis of enzootic pneumonia in pigs, and consequently for increasing their body weight. 2. Veterinary medicinal preparation as an addition to drinking water or animal feed for pigs according to claim 1, characterized in that it contains an antibiotic mixture of 1 mass part of lincomycin and 1 to 3 mass parts of gentamicin sulfate. 3. The procedure for the prophylaxis and therapy of dysentery and colibacillosis and the prophylaxis of enzootic pneumonia in pigs, and consequently for increasing their body weight, indicated by the addition of a veterinary co-medicinal preparation, which contains an antibiotic mixture of 1 part by mass of lincomycin hydrochloride and 1 to 10 parts by mass of gentamicin sulfate and the usual carrier medium in drinking water or animal feed for pigs. 4. The use of a veterinary medicinal preparation as an addition to drinking water or animal feed for pigs, indicated by the fact that it contains an antibiotic mixture of 1 part by mass of lincomycin hydrochloride and 1 to 10 parts by mass of gentamicin sulfate and a common carrier base for the prophylaxis and therapy of dysentery and colibacillosis and the prophylaxis of enzootic pneumonia and consequently to increase their body mass gain. 5. Use of a veterinary medicinal preparation as an additive to drinking water or animal feed for pigs according to claim 4, characterized in that it contains an antibiotic mixture of 1 part by mass of lincomycin hydrochloride and 1 to 3 parts by mass of gentamicin sulfate.