SI9200002A - Cattle food and addition to it or to drinking water, containing antibiotic combination of gentamycine with lincomycine or clindamycine - Google Patents

Description

ANIMAL FOOD AND SUPPLEMENTS OR DRINKING WATERS CONTAINING AN ANTIBIOTIC MIXTURE OF GENTAMICIN WITH LINCOMYCIN OR CLINDAMYCIN

Field of the Invention (MPK A23K 1/17)

The present invention relates to the field of veterinary medicine and relates to animal food and additives to it or to drinking water containing an antibiotic mixture of gentamicin with linkomycin or gentamicin with clindamycin, which may be in the form of free bases, but preferably in the form of their pharmacologically acceptable acid addition salts, for the prophylaxis and therapy of infections and, consequently, for the increase in weight gain in fattened animals, as well as for the prophylaxis and therapy of infections, and consequently for the increase in weight gain in fattened animals.

A technical problem

There is a continuing need for effective prophylaxis and therapy of infections and, consequently, for weight gain in fattened animals such as poultry, calves, pigs, lambs, and antibiotics and / or combinations of antibiotics are sought in this regard, as additives to animal feed or drinking water, to bring about the desired success.

The state of the art

Linkomycin is a known antibiotic that has been described in U.S. Pat. 3086912, which inhibits the growth and reproduction of many microorganisms, in particular gram positive bacteria. In U.S. Pat. 3155580 describes galenic forms based on lincomycin or its acid addition salts, as an active ingredient for the treatment of bacterial, human and animal infections. In fattened animals, the antibiotic can be used prophylactically or for weight gain as a growth promoter. Linkomycin hydrochloride may be administered to normal animal feed in dosage units.

From U.S. Pat. 3150042 is known for the use of linkomycin for the prophylactic and therapeutic treatment of coccidiosis in animals, using an antibiotic as an adjunct to normal animal feed, or to an adequate amount of drinking water. The use of tablets and sterile injectable solutions is also described.

Clindamycin is the generic name for 7 (S) -chloro-7-deoxyline clomycin, which has been described in U.S. Pat. 3475407, no. 3496163, no. 3509127 and no. 3539689 as a base or as an acid addition salt thereof, used in oral or parenteral galenic forms for the treatment of humans and animals infected with bacteria, coccidia and mycoplasma.

The therapeutic forms of clindamycin are similar to those used for linkomycin, except that clindamycin is also effective against plasmodia and more effective against bacterial infections. It is also used prophylactically as a feed additive in livestock.

Gentamicin is an antibiotic that has been described in U.S. Pat. 3091572 and no. 3136704 and consists of three structurally related components, gentamicins C _x , C ₂ and C _la . Gentamicin A is also known, which differs from other components of the complex. In galenic forms, gentamicin sulfate (gentamicin sulfate) is present. Gentamicin is a very effective antibiotic against gram-positive and gram-negative microorganisms, such as staphylococcus, klebsiela, pneunomonas and proteus, and is used in both human and veterinary medicine.

In U.S. Pat. 3261687 discloses animal food and weight gain in healthy fattened animals in a ratio of 1 to 10 wt. parts of spectinomycin and 1 wt. portion of linkomycin, in animal feed composition. They state that this combination of antibiotics in animal food or drinking water has produced unexpectedly good results in increasing weight gain and flight speed, as well as in increasing the performance factor. At the same time, the combination of both antibiotics in animal feed works synergistically and is also suitable for the therapeutic and prophylactic treatment of poultry, pigs, sheep and cattle.

Description of a solution to a technical case problem

The invention is based on the task of finding an effective mixture of antibiotics as additives 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 therefore rapidly increase the weight gain of fatteners animals and increased the performance factor, with low food conversion. The results obtained with a new mixture of antibiotics, in addition to animal feed or drinking water, would be better than the results obtained with the use of individual antibiotics, or would exceed some of the known combinations of antibiotics for the same purposes as in the aforementioned U.S. Pat. 326187 said combination of linkomycin-spectinomycin, which would represent a valuable improvement in animal husbandry.

Surprisingly, we have found that the desired target is achieved with a mixture of gentamicin antibiotics with lincomycin or gentamicin with clindamycin, preferably in the form of their acid addition salts, such as a mixture of gentamicin sulfate and lincomycin hydrochloride, and added to normal animal food or drinking water.

It has been found that effective prophylactic and therapeutic effects and, as a result, maximum final body weight are obtained by drinking animals, such as poultry, which contain a combination of gentamicin with lincomycin or clindamycin in drinking water or in conventional foods. Gentamicin sulfate blend with lincomycin hydrochloride is particularly effective.

Compared to the use of the known antibiotic mixture of spectinomycin and linkomycin (Linco-Spectin 100, The Upjohn Comp., USA) in animal feed and Drinking water, or with individual antibiotics, has the highest success factor, in addition to greater weight gain and lower mortality, in a new breed of antibiotics of the invention in animal husbandry. The improved results shown by tests with the new antibiotic blend compared to the known linkomycin-spectinomycin combination were truly surprising, all the more so since very little gentamicin in combination with linkomycin is required to achieve improved results. The results obtained are also important from an economic point of view, since the rearing of fattened animals results in a higher body weight gain, lower mortality and higher success factor, while reducing the total consumption of both antibiotics by using the new antibiotic mix.

Improved results are achieved by using a new blend of antibiotics in livestock breeding such as calves, pigs, lambs and poultry (chickens, ducks, geese, turkeys). Antibiotics are added to normal animal food or drinking water at a ratio of 1 wt. gentamicin and 5 to 60 parts by weight of linkomycin or clindamycin, preferably in the form of their acid addition salts.

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

The antibiotic mixture can be used in the form of pure components or preferably in the form of a liquid or solid premix, that is, in concentrated form, before the addition of food or drinking water. The solid premix can be prepared by mixing antibiotics with solid diluents, such as lactose, starch, flour or. soya flour, calcium carbonate, etc., which is added to food or dispersed in drinking water. Conventional animal foods may also contain supplements such as iodized salt, vitamins A, B, C or D, minerals and other suitable salts, preservatives ...

The new combination of antibiotics works synergistically in prophylaxis and therapy in infections of animals with microparasites, including bacteria, coccidia and mycoplasma, and in particular individual bacteria.

The invention is explained, but they do not limit the following examples:

EXAMPLE 1

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

We performed comparative testing of the above antibiotics in broilers, in order to determine weight gain, growth rate and success factor. Antibiotics were administered in the form of commercial preparations, namely gentamicin powder (LEK-Ljubljana, YU) containing 10% gentamicin, linkomycin-spectinomycin (Linco-Spectin 100, Upjohn Comp., USA) and amoxicillin (Simivet-Pliva, YU). The combination of antibiotics of the invention of linkomycin-gentamicin was administered in the form of a premix with lactose and powdered polyethylene glycol 400.

The antibiotic concentrations used in Table 1 below are calculated by the proportion of individual antibiotics in the preparations or premixtures. The experiment included 69,600 ARBOR-ACRES chicks hatched from the eggs of one group of parents over the same time period. They were placed in 4 facilities (C1, C2, C3 and C4) with 17400 chickens per object.

The animals received the first antibiotic in drinking water for the first three days of life and on days 13, 14, and 15, as can be seen in Table 1.

Table 1.

Object Antibiotic

Age (days) Dose (g / 100 1 drinking water)

Cl gentamicin sulfate 1,2,3 0.5 C2 gentamicin sulfate + 1,2,3 0.5 linkomycin hydrochloride 18,0 C3 linkomycin hydrochloride + 1,2,3 16.6 spectinomycin sulfate 33.35 C4 amoxicillin trihydrate 1,2,3 2.5

At 13.14 and 15 days of age, the chicks were given the same antibiotic concentrations, only in the C4 facility did the concentration of amoxicillin trihydrate increase to 5g per 100 liters of drinking water.

The objects in which the animals for testing were housed were disinfected with the following activities: mechanical cleaning, washing with cold water, washing with hot water (80 ° C), pouring with 0.5% Izosan solution (Lek-Ljubljana), fumigation with 10% aqueous formaldehyde solution. The disinfected facilities were closed for 14 days. The disinfection performance was monitored by microbiological analysis of swabs taken - 10 ³ (Koch's decimal dilution method, i.e. 1000 dilution).

We used 8 to 10 cm thick sunflower seeds for the litter. Before settling the chickens, the litter was disinfected with a 2% aqueous solution of blue gal. The buildings were heated with gas heaters and ventilated with fans, and the temperature controlled by thermostats. The recommended temperature for AA (Arbor-Acres) broilers is as follows:

A week of old 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 AA standard, the daily water consumption is broilers according to different temperatures. Age Amount of water consumed in liters at 21 ° C 1 30 2 60 3 91 4 121 5 155 6 185

The composition of the food used was based on AA norms:

Starter · Finisher Finisher-final

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 % 0.90-1.00 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 CS (coccidiostatic) + + -

AA * weekly weight for broilers is:

Mr

149

371

674

1040

1458

1900 'The AA standard (Arbor Acres) is named after AAF Inc.Glastonbury Connecticut, America's largest poultry producer.

Weights of chickens were monitored by weighing on days 1, 14, 21, 28, 35, and slaughtered at day 42.

The number of animals and the weight of day-old chicks by group are shown in Table 2.

Table 2

Facility Number of chickens. Weight in grams

Cl 17 400 43 C2 17 400 37 C3 17 400 40 C4 17 400 41

The table shows that at the beginning of the tests, the chicks in the Cl object were the heaviest, followed by the chicks from the C4 objects and then C3, and the lightest ones were the chicks in the C2 object. The difference between the maximum and minimum weight is 6 g.

The health status of chickens by groups was monitored by clinical pathoanatomical and bacteriological examinations. A sample of the internal organs of five animals was taken once each week for bacteriological examination.

Animals were vaccinated at 14 days of age against Newcastle disease (application to water).

Test results

The results of weighing the chicks on the first day of age and in subsequent breeding weeks are shown in Table 3.

Table 3:

Obj. Body mass Body mass Body mass Body mass DSP (g) 1.week 2.week 3.week (N = 149g) (N = 371g) (N = 674g)

Cl 43 141 361 666 C2 37 139 373 682 C3 40 144 362 666 C4 41 137 352 655

Object Body weight 4.week (= 1040g) Body weight 5.week (N = 1458g) Body weight 6.week Cl 1040 1466 1840 C2 1114 1490 1870 C3 996 1432 1850 C4 986 1457 1770

N = AA norm for body weight over a period of time

DSP = day old chicks

The weekly weight gain of chickens by group is shown in Table 3A.

Table 3A:

Obj. Weight dsp 1 .day Prir.tel.m. Prir.tel.m. Prir.tel 1.week (g) 2.week (g) 3.week Cl 43 98 220 305 C2 37 102 234 309 C3 40 104 218 304 C4 41 96 215 303

Object Prir.tel.m. Prir.tel.m. Prir.tel.m. 4.week (g) 5.week (g) 6.week (g) Cl 374 426 374 C2 432 376 380 C3 430 436 418 C4 331 471 313

It is clear from both Tables 3 and 3A that in the first week the chickens did not reach the norms of body weight in either of the experimental groups. The highest weight gain was achieved by chickens in facility C3 and the lowest in facility C4.

In the second week, chickens from the C2 facility had the highest body weight and exceeded the norm by 2 grams. In other facilities, the chickens did not meet the norms for weight gain. Chicks from the Cl and C3 facility achieved approximately the same weight and were around lOg below the norm. Again, the worst weight was given to chickens from the C4 facility, and they fell behind the 19g standard.

In the third week, the chickens from the C2 facility again had the highest weight and were the only ones to reach and exceed the standard by 8g. Chicks from Cl and C3 establishments achieve exactly the same weight in the same time period, 8g below the standard.

The chicks in the C4 facility still have the lowest weight (19g below standard).

In the fourth week, chickens in the Cl facility achieved body weight according to AA, and chicks from the C2 facility exceeded it by 74g. Chicks from C3 facility were 44g below standard and from C4 facility by 54g below AA standard.

At the fifth week of age, the weighing results in the C2 facility again exceeded the AA standard by 32g, in the Cl facility by only 8g, and the body weight in the C3 and C4 facility did not reach the AA standard.

The highest final weight, which is also the most economically interesting item, was reached by chicks from the C2 visit, although they had the lowest body weight at the time of settlement. According to body mass data at slaughter, the C3 and Cl object are then followed, while the C4 object deviates from C2 according to the final weight data for lOOg.

Data on food conversion are shown in Table 4 (Conversion tells us how much food is needed per 1 kg of body weight gain)

Table 4:

Object kg

Cl

C2

C3

C4

1.96

1.96

1.94

2.05

In chicken farming, conversion is a very important factor.

The table above shows that the least feed for chickens from C3 facility (l, 94kg), from Cl and C2 0.02g more and from C4 facility 0, 11g more feed was consumed per kg of growth.

Data on weekly mortality of chickens by facilities are shown in Table 5.

Table 5:

Age Death in obj. Death in obj. Death in obj. Death v ob j. (these days) Cl (%) 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 common 6.21 4.63 5.99 5.34

In the second and third weeks, we see in the table a fairly uniform death in all facilities. The clinical and pathological picture was equally balanced. The chickens were killed mainly due to strokes and ascites (watermill), but also due to feverishness. Towards the end of the third week, some chickens with swollen head disease were observed in the C3 facility and also slightly higher deaths (chicken does not see, water and food do not occur, ).

In the fourth week after the death toll, the C3 facility stands out. We mentioned earlier that towards the end of the third week we saw chickens with swollen heads, the number of them increased greatly ^ and thus the deaths. The second problem in this facility is cachexia.

In other facilities, ascites and cachexia are the main problems.

In the sixth week, death generally rises especially in the C4 facility, where the classic form of CRD (Cronic respiratory disease) occurs, as well as ascites and cachexia. In the C3 facility, the number of cases of swollen heads has subsided, with ascites and cachexia being the main problem, as well as some cases of CRD.

Cachexia and some cases of CRD occur in the CI and C2 facility.

Success Factor Say (I)

Comparison of data on total mortality, final weight, and group-by-group conversion is shown in Table 6.

Table 6

CI C2

C3 C4 total death (%) 6.21 4.63 5.99

5.34 body final

weight (kg) 1.84 1.87 1.85 1.77 conversion 1.96 1.96 1.94 2.05 the success factor 1,992 2,098 th most common 2,007 th most common

1,844 th most common

Table 6 shows three performance indicators for each breed (death, weight, conversion). However, it is precisely when we inspect these that we can get a false picture of the success of a particular breeding. So we have a performance factor that tells us exactly which breeding is most successful.

The table shows that object C2 has the highest performance factor, followed by object C3, and CI and C4.

The quantities of meat obtained, the consumption of feed and the quantities of meat lost as a result of death are shown in Table 7. (calculated per 1000 animals).

Feed = heavier x meat conversion = 71% of broilers

Table 7:

CI C2 C3 C4 Quantity obtained 1306 1327 1313 1256 meat (kg) Food Consumption (kg) 3600 3660 3580 3628 The amount of lost meat due to death (kg) 80 61 77 66

The table above shows that as you gain weight, feed consumption increases. The only exception is the C4 facility, where despite its low weight, high food consumption.

Conclusion

Total mortality is lowest in the group receiving the combination of antibiotics of the invention, i.e., linkomycin-gentamicin (object C2) 4.63%, followed by amoxicillin trihydrate (object C4) 5.43%, combinationomomycinspectinomycin (object C3) 5, 99% followed by gentamicin (CI facility) 6.21%.

The final body weight was highest in the group receiving the linkomycin-gentamicin combination (object C2) l, 87kg, followed by the combination of linkomycin-spectinomycin (object C3) l, 85kg, gentamicin (object CI) l, 84kg followed by amoxicillin trihydrate (object C4) l, 77kg, which deviates significantly from the other three groups.

The performance factor was highest in the group receiving the combination of antibiotics linkomycin-gentamicin (object C2), followed by object C3 and finally CI and C4.

Conversion was lowest in the group treated with the combination antibiotic linkomycin-spectinomycin (object C3) 1.94 kg of feed per 1 kg increment, in the group tested with the combination antibiotic linkomycin-gentamicin the conversion value was 1.96 the same as in the group tested with gentamicin. The antibiotic-treated group, amoxicillin, however, consumed the most feed per kg of growth (2.05).

EXAMPLE 2

Preparation for the treatment and breeding of animals

Linkomycin hydrochloride 360g Gentamicin sulfate lOg polyethylene glycol 4000 powder 40g lactose 590g

l.OOOg

The preparation is prepared by mixing fine-grained solids in a blender, which can then be added to drinking water or animal feed. <\

Claims (9)

PATENT APPLICATIONS 1. Animal food and additives thereto or drinking water, characterized in that it contains an antibiotic mixture of 1 part by weight of gentamicin and 5 to 60% by weight. parts of lincomycin or clindamycin or their pharmacologically acceptable acid addition salts, for the prophylaxis and therapy of infections and, consequently, for the gain of weight gain in fattened animals. 2. Animal food and additives to it or drinking water according to claim 1, characterized in that it comprises gentamicin sulfate and lincomycin hydrochloride or clindamycin hydrochloride as an antibiotic mixture. 3. Animal food and its additive or drinking water according to claim 1, which contains 1 wt. part of gentamicin sulfate and 5 to 60 wt. parts of lincomycin hydrochloride. 4. Animal feed and supplement to it or drinking water according to claims 1 to 3 in poultry farming. 5. Animal food and its or drinking water additives according to claims 1 to 4, characterized in that it contains 0.1 to 5g of gentamicin sulfate and 0.5 to 30g of linkomycin hydrochloride in 100 1 of water. 6. Process for preparing animal feed and its additives or drinking water, characterized in that 1 wt. gentamicin portion, 5 to 60 wt. parts of lincomycin or clindamycin, or a pharmacologically acceptable acid addition salt thereof, and a customary water-soluble carrier. 7. A process for preparing an animal feed and its additive or drinking water according to claim 6, characterized in that 1 wt. part of gentamicin sulfate and 5 to 60 wt. parts of lincomycin hydrochloride and the usual water-soluble carrier base. 8. Use of animal feed and its additive or drinking water, characterized in that it contains 1 wt.% As an antibiotic mixture. gentamicin and 5 to 60 parts by weight of linkomycin or clindamycin or their pharmacologically acceptable acid addition salts, for the prophylaxis and therapy of infections and, consequently, for the increase in weight gain in fattened animals. 9. The use of animal feed and its additives or drinking water according to claim 8, characterized by the fact that it contains 1 wt. part of gentamicin sulfate and 5 to 60 wt. parts of lincomycin hydrochloride for the prophylaxis and therapy of infections and, consequently, for the increase in weight gain in poultry.