FI61266C - FODERSAMMANSAETTNING VILKEN ANVAENDS SAOSOM HUVUDFODER TILLSATSFODER ELLER FODERBLANDNING - Google Patents

Description

R5F * 1 rb1 (11jAdvertisement ^ 19 66 JS · LBJ (11) UTLÄGGNINGSSKRIFT 0 1 ^ ° 0 ¢ ^ 45) Patent granted 12 07 1902

Patent meddelat ^ (51) Ky.lk.3 / lnt.CI.3 a 23 K 1/17 FINLAND —FINLAND (21) P * t «flttlh.k.mu.-P« «« W.eknlng 762580 (22 ) Hakamltpltvl - AmMuilngtdaf 00.09-76 (23) Alkuptlvi — Gllclgh «ud« g 08.09 * 76 (41) Tullut JulklMkfl - Bllvlt offantllg 12.03-77 _. . '. . , (44) Date of departure and date of issue. - Λ_ Qo

Patent and registration authorities Ans6kan uttagd och utl.akrlftan publkarad 31.03.82 (32) (33) (31) Requested privilege —Begird prkwltet 11.09 * 75

Federal Republic of Germany-Förbundsrepubliken

Tirskland (DE) P 25 ^ 0509-8 (71) Hoechst Aktiengesellschaft, 6230 Frankfurt / Main 80, Federal Republic of Germany-Förbundsrepubliken Tyskland (DE) (72) Fritz Bauer, Bad Soden / Taunus, Gunter Dost, Kelkheim / Taunus, Federal Republic of Germany-Förbundsrepubliken Tyskland (DE) (7 ^) Oy Kolster Ab (5 * 0 Composition of feed used as feed, compound feed or compound feed -Fodersammansättning, vilken används säsom huvudfoder, tillsatsfoder eller foderblandning

It is known that antibiotics are added to feed for animal consumption.

Suitable antibiotics, such as bacitracin, oleandomycin and virginiamycin, are used primarily in animals with a single-cavity stomach and have no particular effect on digestion in the rumen of ruminants. It has now been found that the salinomycin-containing substances according to the invention have a special effect on cellulose-digestible animal species, since they have a particularly advantageous effect on the microculture which is essential for this digestion.

The present invention therefore relates to the use of salinomycin and its physiologically acceptable salts and esters as feed for ruminants and other animal species.

The invention is characterized in that the feed composition contains salinomycin or a physiologically acceptable salt and / or ester thereof in a concentration corresponding to a daily dose of 0.02-5.0, preferably 0.1-1.0 mg / kg body weight.

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The invention relates in particular to improved feed materials for animals with the digestive physiology of ruminants, i.e. capable of digesting crude fibers or cellulose, and the above definition therefore means not only ruminants as such but also, for example, horses and rabbits.

Salinomycin, its salts and esters are described, for example, in GB Patent No. 1,378,413 and in DE-A-2,353,998. They also mention its use as an anticoccidial agent.

Physiologically acceptable salts or esters which can be used instead of or with salinomycin according to the invention are, for example, alkali metal salts, in particular sodium, potassium or ammonium salts, alkaline earth metal salts, in particular magnesium or calcium salts, and alkyl esters, in particular those having 1- 8, preferably 1 to 4 carbon atoms, and a benzyl ester.

According to the invention, it has been found that feeds containing salinomycin improve feed utilization in ruminants and accelerate the growth of animals. Better utilization of feed means that a certain amount of feed achieves a certain weight gain. In addition, it was found that in ruminant rumen the ratio of acetic acid, propionic acid, butyric acid changes when the substances according to the invention are administered in the form of feed, so that the proportion of propionic acid valuable for energy metabolism increases at the expense of acetic acid and butyric acid. It is particularly important that this effect is also achieved with NPN (non protein nitrogen) compounds, which are currently used as a nitrogen source of protein in ruminant feed, such as urea, biuret, diammonium phosphate and the like.

Not only as a pure substance, salinomycin can be similarly used as an active ingredient as a dried mycelium or crude product.

In many cases, the preferred form of administration of the active ingredient is a concentrate to be added to the feed. Such a concentrate or premix can be prepared, for example, by mixing the active ingredient or the active ingredient-containing fungal mycelium or crude product with a physiologically acceptable solid or liquid carrier. Examples of solid carriers which may be used are cereal by-products, such as wheat flour, wheat bran or rice bran, from which oil has been removed, as well as maize flour, soya flour, Bolus Alba or calcium carbonate. Physiological saline solutions, distilled water and physiologically acceptable organic solvents can be used as liquid carriers. Likewise, suitable additives such as emulsifiers, dispersants, suspending agents, wetting agents or coagulants can be added. These concentrates usually contain about 0.5-5% of active ingredient, but may be higher or lower depending on the intended use.

When administering feed materials, the process is carried out as appropriate by adding the premix to the feed by mixing, stirring, shaking, grinding and the like. way. The use of a powdered concentrate has proved to be particularly advantageous.

The substances according to the invention can be added to the supplementary feed or to the complete feed or also to only a part of the daily ration.

The feed to which the active ingredient according to the invention is added is a feed conventionally used in the feeding of ruminants, such as, for example, barley, oats, maize, as well as rackets, hay or a compound feed made therefrom. It is also possible to use ordinary compound feeds or mineral mixtures, salt arrow sites, feed packs and liquid feed as feed materials. Complementary feed for cattle may include dry chips, cornmeal, soybean meal, molasses and oat bran as the main ingredient, as well as a mineral mixture, wheat bran and urea, or licking salt for sheep, such as bone meal and cooking salt.

Another way of supplying the active ingredient is to add it as such or in the form of its concentrate or suspending powder to drinking water or to another beverage such as milk.

Mixing with feed may also be by direct oral administration to animals during or after feeding of a substance of the invention, for example in the form of a solid or liquid preparation such as a tablet, capsule, granules, pill, juice or syrup, or a concentrate as described above. . In this way, the important mixing of the feed according to the invention takes place immediately after its administration in the stomach, and in the same way the result according to the invention, considerably improved food utilization and increased growth are achieved.

The amount of substances according to the invention depends on the classification method. It can always be 0.5-500 mg / kg of feed, i.e. corresponding to 0.02-5.0 mg salinomycin per kg body weight per day. The amount of salinomycin in the feed is preferably selected to correspond to a dosage of 0.1-1.0 mg / kg body weight and per day. But 4 61266 is, of course, possible to significantly exceed the limits indicated in appropriate cases. If the active ingredient is administered to the animal immediately as an oral preparation, the dosage must then be chosen to correspond to the above amounts per kilogram of body weight and per day. Thus, for example, preparations administered directly orally to an adult bovine animal will contain from about 10 to about 500 mg of the active ingredient salinomycin. Preparations intended for smaller ruminants, such as sheep or goats, contain correspondingly smaller amounts of active ingredient.

The following examples are intended to illustrate the invention. Example 1

A feeding experiment was performed using salinomycin on 12 slaughter bulls kept tethered in a barn in single feeding and had an automatic supply of drinking water. Six animals formed the salinomycin experimental group, 6 animals the untreated control group. The average weight of the animals at the start of the experiment was about 350 kg. Duration of the experiment 8 weeks, individual weighing every 2 weeks. The feed consisted of concentrates fed in increasing amounts according to the animals' nutritional needs (2-4 kg per animal and day), as well as silage fermented corn feed (16-20 kg per animal and day). Coal feed:

Barley 26%

Oats 20%

Corn 45%

Calcium carbonate 2%

Hostaphos (Na-Mg-Ca phosphate) 4%

Urea 2%

Sodium bicarbonate 1% 100%

Feed units 657 feed units

Protein 11.1%

The dosage of salinomycin was chosen by administering 100 mg of antibiotic per animal and per day as a 2% concentrate in cornmeal as a feed (in the form of flour).

Table 1 compares the weight gains in the experimental and control groups as well as the improvements in salinomycin results.

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Table 1 61266

Duration of the experiment Mean Mean Weight gain per week Weight gain Weight gain Increase in the experimental group in the control group in the experimental group Percentage in the group 2 14.8 21.3 + 43.9% 4 35.3 39.0 + 10.5% 6 54.8 62.2 + 13 .5% 8 61.5 68.7 + 11.1%

Table 2 compares the dietary intake of the experimental group and the control group as well as the improvement due to the use of salinomycin:

Table 2

Duration of the experiment Mean Mean Improvement in salino week Utilization rate Utilization rate due to mycine + in the comparison group of experimental groups as a percentage 2 3 264 1 865 + 42.9% 4 2 843 2 295 + 19.3% 6 2 777 2 249 + 19.1% 8 3 307 2 777 + 16.0%

Tables 3 and 4 show how the amount of lower molecular fatty acids in the rumen fluid has changed over the 8 experimental weeks in the salinomycin group compared to the control group. In determining these values, test samples were taken by probe and gas chromatographed.

Table 3

Fatty acid type After 8 test weeks, the average amount of fatty acids per 100 ml of rumen fluid in mg

Control group Experimental group C2 190.73 135.65 C3 53.90 80.75 C4 41.92 19.72 ...... I ----- '' .....- ------ II '-------' · 6

Table 4 61266

Fatty acid species Percentage of private fatty acids in rumen fluid after 8 test weeks

Comparison group Experimental group C2 66.56 57.45 C3 18.80 34.20 C4 14.92 8.35 100% 100%

Tables 3 and 4 show that the proportion of propionic acid (C 1-4) valuable for energy metabolism has increased significantly at the expense of acetic acid (C2) and butyric acid (C4), resulting in significantly better food utilization.

Example 2

A feeding experiment using salinomycin was performed on 22 slaughter bulls and 11 animals formed a control group and 11 animals an experimental group. The animals were kept tethered in the barn, fed individually, and given their own drinking water. Their average weight at the beginning of the experiment was 400 kg, the experiment lasted 6 weeks, and the animals were weighed individually every 2 weeks. The feed consisted of concentrate fed in increasing amounts according to the animals' nutritional needs (2-4 kg per animal and day), as well as corn-fermented corn feed (16-20 kg per animal and day).

Forage composition:

Oats 40%

Corn 24%

Urine content 2%

Sodium bicarbonate 1%

Green alfalfa flour 15%

15% dry section

Mineral Blend (Phosca Bully) 3% 100%

Feed units 586 feed units

Protein 12.4%

The dose of salinomycin in the experimental group was 100 mg per animal and per day and the antibiotic was administered as a 2% concentrate with cornmeal among the feed.

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Table 5 shows the weight gain in the experimental and control groups compared with each other and the weight gain improvements achieved with salinomycin:

Table 5

Duration of the experiment Mean weight Average weekly increase Increase in reference weight gain in the experimental group in kg in the experimental group in% per kg 2 17.3 23.6 + 36.4 4 32.1 35.2 + 9.7 6 49.8 53.6 + 7.6

Table 6 shows the improvements in food utilization in the experimental group and the control group compared with each other and with salinomycin:

Table 6

Duration of the experiment Mean Mean Weekly utilization rate of salinomycin in the control group Utilization rate in the control group% improvement in experimental group 2 3 217 2 363 + 26.5 4 3 477 3 176 + 8.7 6 3 387 3 113 + 8.0

Tables 7-8 show how the amount of lower molecular weight fatty acids in the rumen fluid has changed over 6 experimental weeks in the salinomycin group compared to the control group. The order was made as indicated in Example 1.

Table 7

Fatty acid type After six weeks of testing, the average amount of fatty acids in 100 ml of rumen fluid in mg

Comparison group Experimental group C2 278.80 205.92 C3 78.16 95.55 C4 55.90 26.07

Table 8 61266

Fatty acid type Percentage of private fatty acids in rumen fluid after 6 test weeks

Comparison group Experimental group C2 67.53 62.87 C3 18.93 29.17 C4 13.54 7.96 100% 100%

The same conclusions can be drawn from the increase in propionic acid as in Example 1.

Example 3

A feeding experiment using salinomycin was performed on 25 slaughter bulls (black-headed cattle); the animals were fed individually, given their own drinking water, and kept tethered in the barn. The average weight at the start of the experiment was about 260 kg; duration of the experiment 20 weeks, weighing every 4 weeks.

The feed consisted of concentrates fed in increasing amounts according to the animals' dietary needs (2-4 kg / animal and per day) as well as silage fermented corn feed (16-20 kg per animal and per day).

Forage composition:

Barley 26%

Oats 20%

Corn 45%

Calcium carbonate 2%

Hostaphos (Na-Mg-Ca phosphate) 4%

Urine content 2%

Sodium bicarbonate 1% 100%

Feed units 657 feed units

Protein 11.1%

The animals were divided into the following groups:

Group I: 5 animals without treatment (comparison)

Group 11: 6 animals treated with 100 mg monensin per animal and day.

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Group III: 7 animals treated with 50 mg salino-mycin per animal and day.

Group IV: 7 animals treated with 100 mg salino-mycin per animal and day.

Doses of antibiotics in experimental groups II-IV were administered daily among the feed (in powder form).

Score:

The following table shows the average weight gain and food utilization in the control group and in the 3 experimental groups at each weighing after 4-20 experimental weeks. In addition to the absolute values, relative values compared to the untreated control group (in%) are given in the experimental groups.

Weight development after 20 weeks of treatment with salinomycin 50 or 100 mg / animal and day in a dose-dependent manner increased weight gain by + 10% and + 17.8%, while 100 mg monensin per animal and day resulted in weight gain of only +0 , 2%.

Dietary utilization was improved with both salinomycin doses (as well as dose-dependent) by +9.0 and +15.5, whereas 100 mg monensin per animal and day produced only an improvement of + 5.4%.

Experimental Comparison Monensin Salinomycin Salinothycin duration n = 5 100 mg / 50 mg / 100 mg / weeks initial weight per animal and per animal and per animal and 258.8 kg per day per day per day abs. n = 6 n = 7 n = 7 initial weight initial weight initial weight 261.2 kg 260.7 kg 260.7 kg abs. rel. abs. rel. abs. rel.

kg kg% kg% kg%

Average 4 29.0 34.0 117.2 33.9 116.9 35.9 123.8 weight gain 8 64.2 63.8 99.4 72.6 113.1 74.3 115.7 per animal 12 96 , 4 96.5 100.1 106.2 110.2 112.6 116.8 16 130.2 126.0 96.8 144.9 111.3 150.6 115.7 20 164.6 165.0 100 , 2,181.0 ^ 110.0 193.9 ^ 117.8

Average 4 3 305 2 807 84.9 2 855 86.4 2 647 80.1 in favor of food 8 3 259 3 145 96.5 2 900 89.0 2 793 85.7 in favor of 12 3 462 3 246 93.8 3 145 90 , 8 2 929 84.6 continues ...

a 10 61 266 continued from previous page use 16 3 309 3 412 97.2 3 152 89.8 3 005 85.6 feed units / 20 558 3 366 94.6 3 237 +++ 91.0 3 005h- + 84.5 weight gain per kg +++ Meaning: 99.9% probability Example 4

A feeding trial using salinomycin was performed on 26 bulls for slaughter (red-spotted cattle), fed individually, given their own drinking water and kept tethered in a barn, with an average weight of approximately 225 kg at the start of the trial, 20 weeks duration of the trial, and individual weighings every four weeks.

The feed consisted of concentrate fed in increasing amounts (2-4 kg per animal and day) depending on the animals' dietary needs, as well as corn-fermented maize feed (16-20 kg per animal and day).

Barley 26%

Oats 20%

Corn 45%

Calcium carbonate. 2%

Hostaphos (Na-Mg-Ca phosphate) 4%

Urine content 2%

Sodium bicarbonate 1% 100%

Feed units 657 feed units.

Protein 11.1%

The animals were divided into the following groups:

Group I: 6 animals without treatment (control group)

Group II: 6 animals treated with 100 mg of monensin per animal per day.

Group III: 7 animals treated with 50 mg salinomycin per animal per day.

Group IV: 7 animals treated with 100 mg salinomycin per animal per day.

Doses of antibiotic were administered daily in experimental groups II-IV with a compound feed (in powder form).

612 6 6 11

Score:

The following table shows the average weight gain and food utilization in the control group and 3 experimental groups, each weighing after 4-20 experimental weeks.

In addition to the absolute values, relative values have been given in the experimental groups compared to the untreated control group (in percent).

Weight gain occurred after 20 weeks with salinomycin 50 mg or 100 mg / animal and day in a dose-dependent increase in weight gain of + 17.5% and + 21.7%, whereas with 100 mg monensin per animal and day, the difference in weight gain was only + 2.4%.

Dietary utilization improved with both salinomycins (as well as dose-dependently) by + 12.5% and + 15.4%, whereas 100 mg monensin per animal and day did not result in improvement.

Experimental Comparison Monensin Salincrnyzine Salinomycin duration n = 5 100 mct / el and 50 rag / el and 100 mg / el and time of onset day per day per week per week towards sa ti 225.0 n = 6 n = 7 n = 7 ka initial weight initial weight initial weight 223.8 kg 223.6 kg 224.3 kg abs. abs. rel. abs. rel. abs. rel.

kg kg% kg% kg%

Average 4 27.5 26.4 96.0 30.4 110.6 33.5 121.8 Weight gain 8 54.7 53.2 97.3 62.0 113.4 62.7 114.6 per animal 12 83 .5 86.4 103.5 98.0 117.4 101.0 121.0 16 117.3 122.5 104.4 142.1 121.1 147.6 125.8 20 157.5 161.2 102 , 4 185.0 ^ 117.5 191.7 ^ 121.7

Average 4 2 987 3 014 100.9 2 640 88.4 2 318 77.6 for food 8 8 089 3 114 100.8 2 693 87.2 2 638 85.4 Use of feed units / 12 3 238 3 134 96.8 2 780 85.9 2 691 83.1 weight gain per kg 16 3 228 3 166 98.1 2 739 84.6 2 634 81.6 per 20 3 179 3 175 99.9 2 781 ^ 87, 5 2,691 + ^ 84.6 -J | |

Meaning: 99.9% probability

Example 5

Supplementary feed for cattle

Dry section 30% 61266 12

Corn flour 15%

Soybean meal 15%

Molasses 15%

Oat bran 15%

Wheat bran 2.5%

Urine content 1.5%

Mineral mixture 5.0%

Thus, salinomycin mycelium premix (2.5 mg / g) 1.0% 100% 1 kg of complementary feed contains 25 mg salinomycin. Pasture cattle receive 2-4 kg of supplementary feed per day, i.e. 50-100 mg salinomycin.

Example 6 Arrow salt for sheep

Bone powder 6 kg

3 kg of cooking salt

Salincxnysin mycelium as a 1% premix 1 kg 10 kg 10 g of arrow salt contained 10 mg of salinomycin, i. daily dose of sheep.

Claims (6)

13,612 66 Feed composition for use as a main feed, complementary feed or compound feed, characterized in that it contains salinomycin or a physiologically acceptable salt and / or ester thereof in a concentration corresponding to a daily dose of 0.02-5.0, preferably 0.1- 1.0 mg / kg body weight. Feed composition according to Claim 1, characterized in that the salt is an alkali metal salt or an alkaline earth metal salt. Feed composition according to Claim 2, characterized in that the alkali metal salt is a sodium, potassium or ammonium salt and the alkaline earth metal salt is a magnesium or calcium salt. Feed composition according to Claim 1, characterized in that the ester is an alkyl ester or a benzyl ester. Feed composition according to Claim 4, characterized in that the alkyl ester contains 1 to 8, preferably 1 to 4, carbon atoms. Feed composition according to Claim 1, characterized in that it contains salinomycin as a mycelium or as a raw product.