HRP930004A2 - Animal food, an additive to it, or to drinking water, containing the antibiotic mixture of gentamicin with lincomycin or clindamycin - 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 Patents (IPC), the subject of the invention is classified, i.e. classified and marked with the classification symbol A23K 1/17, which defines animal feed with antibiotics. As can be seen, the invention belongs to the field of veterinary medicine, and relates to animal food and its addition, which contains an antibiotic mixture of gentamicin with lincomycin or gentamicin with clindamycin, which can be in the form of free bases, but always primarily in the form of their pharmacologically acceptable acid of addition salts, for prophylaxis and therapy of infections and consequently for increasing body weight gain in fattened animals as well as for the procedure for prophylaxis and therapy of infections, and as a consequence for increasing body weight gain in fattened animals.

Technical problem

There is a constant need for effective prophylaxis and treatment of infection and, consequently, for increasing body weight gain in fattened animals, such as poultry, calves, piglets, lambs, and for this purpose, antibiotics are sought, or a combination of antibiotics as an addition to animal feed or drinking water, with which would reach the desired success.

State of the art

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. US patent no. 3155580 describes 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 fattened animals, the antibiotic can be used prophylactically, i.e. to increase body weight as a growth stimulator. Lincomycin hydrochloride can be administered in common food in dosage units.

From US patent no. 3150042 is the known use of lincomycin for the prophylactic and therapeutic treatment of coccidiosis in animals, where antibiotics are used as an addition to ordinary animal feed or to an appropriate amount of drinking water. The use of tablets and sterile injection solutions is also described.

Clindamycin is the generic name for 7(S)-chloro-7-deoxy-lincomycin, which was described in US Pat. Nos. 3475407, no. 3496163, no. 3509127 and no. 3539689 as a base, or as its acid addition salts, which in oral or parenteral galenic forms are used in the treatment of humans and animals, infected with coccidio bacteria and microplasma.

Therapeutic forms of clindamycin are used similarly to clindamycin, except that clindamycin is effective against plasmodia and even more effective against bacterial infections. It is also used prophylactically, as a feed supplement for fattened cattle.

Gentamicin is an antibiotic, which was described in US patents no. 3091572 and no. 3136704 and consists of three structurally related components, gentamicin C1, C2 and C1a. Gentamicin A is also known, which differs from the other components of the complex. In galenic forms, gentamicin occurs in the form of sulfate (gentamicin sulfate).

Gentamicin is a very effective antibiotic against gram-positive and gram-negative microorganisms, such as types of staphylococcus, Klebsiella, pneumomonas and proteus, and is used both in human medicine and in veterinary medicine.

In US patent no. 3261687 describes animal feed and a procedure for increasing body weight in healthy fattened animals in a ratio of 1 to 10 parts by mass of spectinomycin and 1 part by mass of lincomycin in the composition of animal feed. They state that with this combination of antibiotics in animal feed or drinking water, they achieved unexpectedly good results in increasing body mass gain and speed of reaching it, as well as in increasing the success factor. At the same time, the combination of antibiotics in animal nutrition acts synergistically, and is also suitable for therapeutic and prophylactic treatment of poultry, pigs, sheep and cattle.

Description of solutions to technical problems

The invention is based on the task of finding an effective mixture of antibiotics as an addition to animal feed or drinking water for animals such as poultry, pigs, calves and lambs, which would be effective in the prophylaxis and therapy of infections, and would consequently increase body weight gain quickly. fattening animals and success factor with low feed conversion.

The results obtained with a new mixture of antibiotics, as an additive to animal feed or drinking water, would be better than the results obtained with the use of individual antibiotics, that is, they would be better than some known combination of antibiotics for the same purposes, as in the above-mentioned US patent no. . 3261687 mentioned the combination of lincomycin-inspektinomycin, which would represent a significant improvement in animal husbandry.

We were surprised to find that the required goal can be achieved with a mixture of antibiotics gentamicin with lincomycin or gentamicin with clindamycin, primarily in the form of their acid addition salts, such as a mixture of gentamicin sulfate and lincomycin hydrochloride, and we add them to common animal feed or drinking water.

We found that we achieve effective prophylactic and therapeutic effects and, as a result, the highest final body mass with fattening animals such as poultry, which in drinking water or in ordinary food contains a combination of gentamicin with lincomycin or clindamycin. A mixture of gentamicin sulfate with lincomycin hydrochloride is especially effective.

In comparison with the use of the well-known mixture of antibiotics spectinomycin and lincomycin (Linco - Spectin 100, the Upjohn Comp., USA) in animal feed, as well as in drinking water, that is, with certain antibiotics, there is a new mixture of antibiotics in the sense of the invention in animal breeding, in addition to a greater increase in body weight mass and less death, is also the highest success factor. The improved results, which the tests showed with the new antibiotic mixture compared to the known lincomycin-spectinomycin combination, were really surprising, and all the more so, because the improved results were already achieved with a very small proportion of gentamicin in combination with lincomycin.

The established results are also significant from an economic point of view, because when breeding fattened animals with the use of a new mixture of antibiotics, we achieve a higher increase in body weight, lower mortality and a higher success factor, with at the same time a lower total consumption of both antibiotics.

We also achieve improved results with the use of a new mixture of antibiotics in the breeding of fattened animals, such as calves, piglets, lambs and poultry (chickens, ducks, geese, turkeys). Antibiotics are added to common animal feed or drinking water in a ratio of 1 mass part of gentamicin and 5 to 60 mass parts of lincomycin or clindamycin, preferably in the form of their acid addition salts.

The dose of the new mixture of antibiotics in food or drinking water is determined according to the type of animal, age, weight and average daily amount of food or drinking water consumed.

We can use the antibiotic mixture in the form of pure components, but it is more convenient to prepare a liquid or solid premix, that is, in the form of a concentrate, before adding it to food or drinking water. We can prepare a solid premix by mixing antibiotics with a solid diluent such as lactose, starch, flour or soy flour, calcium carbonate and others, which we add to food or disperse in drinking water.

Common animal food can also contain additives such as iodized salt, vitamins A, B, C or D and other exemplary salts, minerals, preservatives.....

The new combination of antibiotics works synergistically in the prophylaxis and therapy of animal infections with microparasites, including bacteria, coccidioides and microplasma, especially with certain bacteria.

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

Example 1

Comparative testing of antibiotics gentamicin, combination lincomycin - gentamicin, combination lincomycin - spectinomycin and amoxicillin in broilers.

We performed comparative testing of the mentioned antibiotics in broilers, with which we wanted to determine the increase in body weight, growth rate and success factor. Antibiotics were applied in the form of commercial preparations, namely gentamicin powder (LEK-Ljubljana, YU) with a content of 10% gentamicin, lincomycin-spectinomycin (Linco-SpectinR 100, company Upjohn Comp. USA) and amoxicillin (SimivetR-Pliva YU). We applied the antibiotic combination according to the invention Lincomycin-gentamicin in the form of a premix with lactose and powdered polyethylene glycol 400.

In table 1 below, the listed concentrations of antibiotics are calculated taking into account the proportion of individual antibiotics in the preparations, that is, the premix. In the experiment, we included 69,600 chickens of ARBOR-ACRES provenance, hatched from the eggs of one group of parents in the same time period, we placed them in 4 facilities (C1, C2, C3 and C4) with 17,400 chickens per facility.

The animals were given a specific antibiotic in their drinking water for the first three days of life, and on days 13, 14 and 15, as can be seen from Table 1.

Table l.

[image]

At the age of 13, 14 and 15 days, the chickens received a higher concentration of antibiotics, only in facility C4 we increased the concentration of amoxicillin trihydrate to 5 g per 100 liters of water for chickens.

The facilities in which we housed the animals for testing were disinfected using the following activities: mechanical cleaning, rinsing with cold water, rinsing with hot water (80°C), spraying with a 0.5% solution of IzosanR (LEK - Ljubljana), processing using gas with 10% aqueous solutions of formaldehyde. We kept the facilities that were so exposed closed for 14 days. We controlled the success of the decontamination using the microbiological analysis of the swabs taken - 103 (Koch's method of decimal dilution, that is dilution 1000).

For spreading, we used sunflower husks in a layer of 8 to 10 cm. We disinfected the mat with a 2% aqueous solution of blue galica before settling the chickens. The objects were heated with gas heaters and ventilated with fans, and the temperature was controlled with thermostats. The recommended temperature for broilers according to the norm A A (Arbor - Acres) is as follows:

Week of age Temperature (°C)

1 32 - 35

2 29 - 32

3 26 - 29

4 23 - 26

5 21 - 23

6 21

7 21

According to the norm A A is the daily water consumption in liters per 100 broilers dosed at different temperatures and ages:

Age Amount of water used in

liters at a temperature of 21°C

1 30

2 60

3 91

4 121

5 155

6 185

The composition of the food used was based on A A standards:

Start Duration End

0 - 23 days 24 - 38 days 38 - 42 days (slaughter)

Total proteins % 23.0 20.5 18.5

Total fat % 5-7 5-7 5-7

Ca % 0.95-1.00 0.95-1.00 0.80-0.95

P % 0.45-0.50 0.41-0.50 0.38-0.45

NaCl % 0.30-0.50 0.30-0.50 0.30-0.50

The week of Mr

1 149

2 371

3 674

4 1040

5 in 1458

6 in 1900

* The standard AA (Arbor Acres) is named after the company AAF Inc. Glastonbury Connecticut, America's largest poultry producer.

We monitored the weight of the chickens by weighing them on the 1st, 14th, 21st, 28th, 35th day and at slaughter (42nd day).

The number of animals and the weight of one-day-old chicks according to the groups can be seen from table 2.

Table 2

Facility Number of chicks Weight in grams

C 1 17 400 43

C 2 17 400 37

C 3 17 400 40

C 4 17 400 41

The table shows that at the beginning of the tests, the heaviest chickens were in facility C 1, followed by chickens from facility C 4, and then C 3, while the lightest chickens were in facility C 2. The difference between the highest and lowest weight is 6 g.

We monitored the health condition of the chickens according to the groups using clinical pathoanatomical and bacteriological examinations. Every week, we took a sample of the internal organs of five animals for bacteriological examination.

Animals were vaccinated at 14 days of age against atypical fowl disease (application in water).

Test results

The results of weighing chickens on the first day of age and during further weeks of rearing are shown in Table 3.

Table 3

Object Body mass Body mass Body mass Body mass

DSP (g) 1st week 2nd week 3rd week

(N=149g) (N=371g) (N=674g)

C 1 43 141 631 6666

C 2 37 139 373 682

C 3 40 144 362 666

C 4 41 137 352 655

Object Body mass Body mass Body mass

(=1040g) 4th week 5th week (=1458g) 6th week

C 1 1040 1466 1840

C 2 1114 1490 1870

C 3 996 1432 1850

C 4 986 1457 1770

N = normative AA for body mass in a certain period of time.

DSP = day old chicks

The weekly increase in body weight of chickens according to groups is shown in table 3A:

Table 3A:

Object Weight DSP Increment i.e. mass Increment i.e. mass Increment i.e. mass

1st day 1st week (g) 2nd week (g) 3rd week (g)

C 1 43 98 220 305

C 2 37 102 234 309

C 3 40 104 218 304

C 4 41 96 215 303

Object Increase in mass Increase in mass Increase in mass

4th week (g) 5th week (g) 6th week (g)

C 1 374 426 374

C 2 432 376 380

C 3 430 436 418

C 4 331 471 313

It is evident from both tables 3 and 3A that in the first week the chickens of none of the experimental groups reached the standards in body weight. The highest body mass was achieved by chickens in facility C 3, and the lowest in facility C 4.

In the second week, the chickens from facility C 2 had the highest body mass, exceeding the norm by 2 grams. In the other facilities, the chickens did not reach the standards in terms of body weight gain. Chickens from C 1 and C 3 facilities reached approximately the same weight, and were about 10 g below the norm. Again, chickens from facility C 4 had the lowest weight and were behind the norm by 19 g.

In the third week, the chickens from facility C 2 had the highest weight, and they were the only ones to reach and surpass the norm by 8 g. The chickens from facility C 1 and C 3 reached exactly the same weight in the same period of time, 8 g below the norm.

Chickens in facility C 4 still have the lowest weight (19 g below the norm).

In the fourth week, the chickens in facility C 1 reached the body weight according to the norm AA, and the chickens from facility C 2 exceeded it by 74 g. The chickens from facility C 3 were 44 g below the norm, from facility C 4 by 54 g below. norm AA.

In the fifth week of age, the weighing results in the C 2 facility again exceeded the AA norm by 32 g, in the C 1 facility by only 8 g, the body mass in the C 3 and C 4 facility did not reach the AA norm. The highest final body weight was achieved by chickens from the C 2 facility, although they had the lowest body weight during settlement. According to data on body mass at slaughter, C 3 and C 1 object followed, while C 4 object deviates from C 2 according to data on final body weight by 100 g.

Data on food conversion are shown in table 4:

(The conversion shows us how much food is needed for 1 kg of body weight gain)

Table 4

Object kg

C 1 1.96

C 2 1.96

C 3 1.94

C 4 2.05

Conversion is a very important factor in raising chickens.

From the table above, we can see that for 1 kg of growth, chickens from C 3 facility consumed the least amount of feed (1.94 kg), from C 1 and C 2 facilities 0.2 g more, and from C 4 facility 0.11 g more feed. .

Data on the weekly death of chickens according to groups are shown in table 5.

Table 5

Age Death in obj. He will die in obj. He will die in obj. He will die in obj.

(weeks) C1 (%) C2 (%) C3 (%) C4 (%)

1 1.85 0.56 0.44 0.60

2 0.63 0.52 0.40 0.60

3 0.59 0.69 0.95 0.81

4 0.93 0.79 1.85 0.69

5 0.99 0.77 1.12 0.71

6 1.21 1.30 1.24 1.93

total 6.21 4.63 5.99 5.34

For the second and third week, we see in the table fairly uniform deaths across all facilities. The clinical and pathological picture was also uniform. Chickens died mainly due to dropsy and ascites (dropsy), and also due to indigestion. Towards the end of the third week, we notice in the C 3 facility several chickens with the disease of swollen heads and also somewhat increased deaths (the chicken cannot see, does not reach water and food and dies). In the fourth week, according to the mortality data, object C 3 jumps out. We mentioned before that towards the end of the third week, we noticed chickens with swollen heads, the number of these increased greatly, and thus the mortality. Another problem in that building was cachexia (deterioration). In other facilities, the main problem is ascites and cachexia. In the sixth week, deaths generally increase, especially in facility C 4, where the classic form of CRD ("Chronic respiratory disease") occurs, in addition to ascites and cachexia. In the C 3 facility, the number of cases of swollen heads has stabilized, and the main problem is ascites and cachexia, in addition to several cases of SRD.

Breeding success factor (I)

Comparison of data on total death, final body mass, conversion according to individual groups is shown in table 6.

Table 6

C1 C2 C3 C4

total death (%) 6.21 4.63 5.99 5.34

final body weight (kg) 1.84 1.87 1.85 1.77

conversion 1.96 1.96 1.94 2.05

success factor 1.992 2.098 2.007 1.844

In table 6 we see three indicators of the success of each breeding (mortality, body mass, conversion). However, when examining them, one can get a wrong picture of the success of some cultivation. That's why we have a success factor, which tells us exactly which cultivation is the most successful. In the table we see that object C 2 has the highest success factor, followed by object C3, and C1 and C4.

The amount of mass gained, feed consumption and the amount of meat lost due to death are shown in table 7 (calculated per 1000 animals).

Feed = weight x conversion

meat = 71% from broiler

Table 7

C1 C2 C3 C4

The amount obtained

of meat (kg) 1306 1327 1313 1256

Food consumption (kg) 3600 3660 3580 3628

Amount lost

for meat, deaths (kg) 80 61 77 66

In the table above, we can see that with the increase in body weight, the consumption of feed also increases. The only exception is the C 4 facility, where, despite the low weight, the consumption of food is high.

Conclusion

The total deaths are the lowest in the groups that received the combination of antibiotics according to the invention, i.e. lincomycin-gentamicin (object C 2) 4.63%, followed by amoxicillin trihydrate (object C 4) 5.43%, combinations of lincomycin-spectinomycin (object C 3) 5.99 and then gentamicin (object C1) 6.21%.

The final body weight was the highest in the group receiving the combination of lincomycin-gentamicin (object C 2) 1.87 kg, followed by the combination lincomycin-spectinomycin (object C 3) 1.85 kg, gentamicin (object C 1) 1.84 kg and then amoxicillin trihydrate (object C 4) 1.77 kg, which deviates sensitively from the other three groups.

The success factor is highest in the group that received the antibiotic combination lincomycin - gentamicin (object C 2), followed by object C 3 and finally C 1 and C 4.

Conversion is the lowest in the group treated with the combination of lincomycin-spectinomycin (object C 3) 1.94 kg of feed for 1 kg of gain in the group tested with the antibiotic combination lincomycin-gentamicin, where the conversion value is 1.96, the same as in the group tested with gentamicin . The group that was treated with the antibiotic amoxicillin consumed the most feed per kg of gain (2.05).

Example 2

Preparation for the treatment and breeding of animals

Lincomycin hydrochloride 360 g

Gentamicin sulfate 10 g

Polyethylene glycol 4000 in powder 40 g

Lactose 590 g

1,000 g

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

Claims (9)

1. Animal food and an addition to it or drinking water, characterized by the fact that it contains an antibiotic mixture of 1 part by mass of gentamicin and 5 to 60 parts by mass of lincomycin or clindamycin or their pharmacologically acceptable acid addition salts, for the prophylaxis and therapy of infection and consequently to increase growth body mass in fattened animals. 2. Animal feed and addition to it or drinking water according to claim 1, characterized in that it contains gentamicin sulfate and lincomycin hydrochloride or clindamycin hydrochloride as an antibiotic mixture. 3. Animal feed and addition to it or drinking water according to claim 1, which as an antibiotic mixture contains 1 mass part of gentamicin sulfate and 5 to 60 mass parts of lincomycin hydrochloride. 4. Animal feed and addition to it or drinking water according to requirements 1 to 3 for poultry farming. 5. Animal feed and addition to it or drinking water according to claims 1 to 4, characterized in that it contains 0.1 to 5 g of gentamicin sulfate per 100 1 of water and 0.5 to 30 g of lincomycin hydrochloride per 100 1 of water. 6. A procedure for prophylaxis and therapy of infection and consequently for increasing body weight gain in fattened animals, characterized by the fact that it includes feeding with animal feed and addition to it or drinking water, which contains 1 mass part of gentamicin and 5 to 60 mass parts of lincomycin or clindamycin or its acid addition salts. 7. The method according to claim 6, characterized in that it includes feeding poultry with animal feed and an additive to it or drinking water, which contains 1 mass part of gentamicin sulfate and 5 to 60 mass parts of lincomycin hydrochloride. 8. Use of animal food and addition to it or drinking water, indicated by the fact that the antibiotic mixture contains 1 part by mass of gentamicin and 5 to 60 parts by mass of lincomycin or clindamycin or their pharmacologically acceptable acid addition salts, for the prophylaxis and therapy of infections and consequently to increase growth body mass in fattened animals. 9. Use of animal feed and addition to it or drinking water according to claim 8, characterized by the fact that it contains 1 part by mass of gentamicin sulfate and 5 to 60 parts by mass of lincomycin hydrochloride for prophylaxis and therapy of infections, and consequently for increasing body weight gain in poultry.