CS239619B1 - Means for feeding feed for livestock with growth stimulating effect - Google Patents

Abstract

The product contains as active ingredients cyanoacetylhydrazone-2-formylquinoxaline-1,4-dioxide (generically designated as Cyadox) in combination with antibiotics or sulfonamides and is excellently suited for suppressing and preventing microbial infectious diseases, especially of the digestive tract, significantly improving the overall health of animals, weight gain and improving feed conversion.

Description

The invention relates to a composition for medicating feed for farm animals with a strong growth-stimulating effect, which, as a carrier and/or excipient, optionally contains other additives. It contains cyanoacetylhydrazone of 2-formylquinoxaline-1,4-dioxide (generically designated as Cyadox) as one of the active ingredients.

The composition according to the invention is excellently suited for suppressing and preventing microbial infectious diseases, especially of the digestive and respiratory tract, coccidiosis, and at the same time stimulates the growth of livestock and improves feed conversion. The composition according to the invention significantly improves the overall health of animals, reduces mortality, increases weight gain and feed utilization.

These new compositions serve primarily as additives to feeds and feed mixtures for livestock, such as pigs, calves, poultry and others, and can be used both to treat infested livestock and for prevention, while also stimulating growth and improving feed conversion.

It is known from the literature (AO No. 195 508; US Pat. No. 4 225 604; DE Pat. No. 2 829 580) that Cyadox is effective against gram-positive and gram-negative microorganisms and has significant coccidiostatic effects and is highly effective as a growth stimulant for livestock. Its great advantage is that it is a practically non-toxic substance, since its LD^q = 15 g/kg (rat).

The use of a number of antibiotics of various types for the treatment of infectious diseases and as growth stimulants in livestock is generally known. The use of sulfonamides for the control of infectious diseases in animals is also well known. However, not all antibiotics used have stimulatory activity. For example, neomycin itself does not act as a growth stimulant (GB Pat. No.

140 315). Sulfonamides generally do not have growth-stimulating activity.

It has now surprisingly been shown that combinations of Cyadox with certain antibiotics, such as tylosin, bacitracin, oxytetracycline, chlortetracycline, flavomycin, virginiamycin, spectinomycin, thiamulin or apramycin, and combinations of Cyadox with certain sulfonamides, such as phthalazole (2-/N-phthalylsulfanylamino/thiazole) or sulfadimidine (4,6-dimethyl-2-sulfanilamidopyrimidine), have unexpected advantages. For example, when Cyadox alone at a dose of 100 ppm/kg feed and tylosin alone at a dose of 100 ppm/kg feed and a combination of 100 ppm Cyadox + 100 ppm tylosin are administered to early weaned piglets, both weight gain and feed conversion are higher in the combination than the sum of the effects of the individually administered components. This is a true synergistic effect that could not have been predicted in advance.

An analogous effect was observed when applying feed medicated with the Cyadox-sulfonamide combination. For example, when Cyadox alone at a dose of 100 ppm/kg feed and phthalazole alone at a dose of 100 ppm/kg feed and a combination of 100 ppm Cyadox + 100 ppm phthalazole per kg feed are applied to pigs in pre-fattening weighing around 50 kg, compared to the untreated control, the weight gain in the combination is higher than the sum of the effects of the individual components.

Again, a synergistic effect is evident here.

The term tylosin in this document means the beech base, or the corresponding amount of salt with acids, such as hydrochloride, sulfate, phosphate, tartrate, or dried fermentation broth with the antibiotic. The term bacitracin means the substance as such or its complex compounds with metals, for example Zn-bacitracin. Similarly, the other antibiotics and sulfonamides mentioned are understood here as such, i.e. amphoteric, basic or acidic substances, but also as pharmaceutically acceptable salts with organic or inorganic acids or bases, or complex salts, or chelates, or as mycelium containing the antibiotic.

Due to the very low toxicity of Cyadox and the mentioned antibiotics and sulfonamides, there is no risk of harm when applying the composition according to the invention in the event of an unintentional overdose of medicated feed, and when applied as a veterinary medicine, appropriate doses can be used to suppress infectious diseases in infected farms, especially in bacterial enteritis, coccidiosis and systemic diseases in general.

The synergistic composition according to the invention may contain a mixture of Cyadox and an antibiotic, or Cyadox and a sulfonamide in any mutual weight ratio, for example in the range of 1:10 to 10:1, in particular approximately 1:1, but may contain both an antibiotic and a sulfonamide in addition to Cyadox. In the preparation of medicated feeds, this mixture is preferably added in the form of a premix to nutritionally balanced feed mixtures with biofactors in an amount of 20 to 500 g of each component per ton of feed, or in a suitable veterinary pharmaceutical form in an amount of 1 to 100 mg of active ingredients per 1 kg of live weight per day.

Dosage forms suitable for the application of the synergistic agent according to the invention may be solid or liquid, e.g. granules, capsules, boli, oral pastes, suspensions, etc., and may contain compatible solvents or thickeners, carriers of organic or inorganic origin, e.g. ground limestone, kaolin, talc, starch, sugars, cellulose, ground plant residues and similar substances usually used for the preparation of dosage forms, as well as conventional excipients, or other pharmaceutically active substances. Of the excipients, it is particularly necessary to emphasize the addition of pharmaceutically suitable surfactants, such as non-ionic, cationic or anionic surfactants with good emulsifying, dispersing and wetting properties, or mixtures thereof. Surfactants may also form part of premixes and feed mixtures and may be selected from a large number of known compounds. Surfactants are added in an amount of 0.5 to 10 kg per ton of feed.

Application forms of the synergistic mixture according to the invention, such as conventional veterinary dosage forms, as well as premixes, concentrates, feed mixtures containing the necessary biofactors, and other preparations of this type, are produced in a known manner, e.g. by thorough mixing or grinding of active ingredients with solvents, thickeners, carriers, excipients, biofactors, surfactants.

The invention also relates to the use of a synergistic composition according to the invention.

The synergistic composition according to the invention can be advantageously used for the treatment and prevention of diarrheal diseases and salmonellosis in pigs and other livestock, coccidiosis and other systemic diseases. This composition also stimulates the growth of livestock, to a greater extent than its individual components, improves feed utilization and the overall health of animals, prevents losses due to animal mortality in the early stages of life, and thus increases the efficiency of large-scale poultry, pig and cattle farms.

The following examples illustrate the use and effectiveness of the invention, but do not limit its numerous possible variations and its scope.

Example 1

Early weaned piglets, crosses of the Noble White x Landrace breed, born within 6 days, were brought from the farrowing house on the 5th day after weaning and after another 7 days of adaptation period at the biostation, the actual experiment was started. The piglets were divided into boxes in groups of 8 to 12 pieces. The boxes were equipped with a slatted floor and wooden heated floors. For the entire 4 weeks of the experiment, all groups were fed a complete mixture for early weaned piglets ČOS 2. The mixture used in the experimental groups was enriched with active substances through the addition of biofactors (premix) as follows:

Group I. - control, mixture alone

II. - Cyadox at a dose of 100 mg per 1 kg of mixture

III. - technical tylosin in a dose of 100 mg of active substance (base) per 1 kg of mixture

IV. - Cyadox at a dose of 100 mg per 1 kg of the mixture in combination with technical \tylosin at a dose of 100 mg of active substance (base) per 1 kg of the mixture.

The animals were weighed individually at the beginning and at the end of the experiment (day 28). Feed consumption was monitored daily by individual groups and feed conversion was calculated on this basis. The overall health of the piglets was monitored daily. The results are summarized in the following table.

Table No. 1

Group I. II. III. IV. Substances used Check Cyadox Tylosin Cyadox <100) + (doses in ppm) (01 (100) tech. (100) Tylosin those. <100) Number of piglets 12 12 11 5x8 Duration of the experiment in days 28 28 28 28 Initial weight x (kg) 10.30 10.28 9.13 7.10 Increase Index (%) 100.00 109.80 125.90 150.60 Conversion of mixture x 2.0 1.99 1.90 1.61 Index (%) 100.0 99.5 (0.5) 92.2 (-7.8) 84.3 (-15.7)

Example 2

In pig fattening, a stationary occurrence of bloody diarrhea is observed in 20 to 25% of animals. These are pre-fattening pigs of the BU x PC + L breed, weighing about 50 kg, housed in pens of 10 to 15 pigs. The diagnosis of the disease was determined on the basis of pathological-anatomical, bacteriological and bacterioscopic examination. Vibrio coli was found to be the causative agent of the diarrheal disease.

Experiment organization: Pigs were divided into 4 groups with different numbers of animals (see Table 2) and fed with a SOL mixture, to which active substances were added in the form of a premix as follows:

Group I - SOL mixture itself

II. group - Phthalazole 100 ppm

Group III - Cyadox 100 ppm

Group IV - combination Cyadox 100 ppm + Ftalazol 100 ppm

The substances were applied for 14 days. In groups III. (Cyadox) and IV. (Cyadox + Ftalazol) no bloody diarrhea was observed, the tested substances had a 100% therapeutic effect. In groups I (control) and II (Ftalazol) bloody diarrhea was observed in 20 to 30% of the animals. At the end of the experiment, 20 pigs from both groups had to be sent for compulsory slaughter due to poor health (from group I. 15, from group II. 5 pigs). The health status and weight gains of the animals treated with the mixture according to the invention compared to the other groups are evident from the following table No. 2.

Table No. 2

Group I. II. III. IV. Substances (doses in ppm in feed) Check (0) Phthalazole (100) Cyadox (100) Cyadox + Phthalazole (100) (100) Number of pigs 73 20 12 74 Duration of the experiment in days 14 14 14 14 Initial weight x kg 50.48 50.62 47.80 53.13 Final weight x kg 59.43 59.61 57.90 64.93 Total gain x kg 8.95 8.99 10.10 11.80 Daily gain x g 639 642 721 843 Increase index in % 100 100.5 112.8 131.8

Example 3

In the farrowing house, MMA syndrome, bronchopneumonia occur in sows and diarrheal diseases occur in piglets. The occurrence of diarrhea is regular during weaning of piglets.

Experiment organization: Weaned piglets of the BD x L breed weighing 7 to 12 kg were housed in two pens of 18 pigs each. One pen served as a control, in the other pen 1% by weight of a premix containing 1.0% by weight of Cyadox and 1.0% by weight of tylosin was added to the feed mixture ČOS 1 and ČOS 2, which corresponds to doses of 100 ppm Cyadox and 100 ppm tylosin. Piglets were individually weighed before the start of the experiment and on the 22nd day after the end of the experiment.

After placing the weaned piglets in the pen, diarrhea was observed in approximately 40% of the piglets in both groups within 48 hours. In the experimental group, diarrhea disappeared as early as the 3rd day after placement in the pen. The piglets were in good health, with no clinical signs of illness until the end of the experiment.

In the control group, diarrhea persisted until day 11 of the experiment. The rapid cessation of diarrhea in the experimental group was reflected in weight gain and also in feed conversion, as can be seen from Table 3.

Table No. 3

Group Tentative Control Duration of the experiment 22 days 22 days Dose of substances in feed Cyadox 100 ppm Tylosin 100 ppm - Initial weight x in kg 9.61 9.58 Final weight x in kg 21.30 18.19 Total gain x in kg 11.69 8.61 Daily gain x in kg 0.530 0.390 Index x of the increase in % 135.89 100.0 Feed conversion in kg 1.59 2.03 Index in % 78.33 100.0

Example 4

On a pig breeding and fattening farm, regular occurrences of colienterotoxemia are observed from the 5th to the 7th day after weaning piglets into pens, bronchitis and bronchopneumonia, scurvy and parakeratosis.

Weaned piglets, PC x L x D breed, weighing 7 to 10 kg, were housed in groups in pens. The piglets were divided into two groups of 33 and individually weighed before the start of the experiment and on the 21st day (after its completion). When placing the weaned piglets in the pens, all piglets were treated with Axetocal (an injectable vitamin preparation). The test preparation was administered in the form of a premix containing 1.0% by weight of Cyadox and 1.0% by weight of tylosin and added in an amount of 1% by weight to the feed mixture ČOS 1 and ČOS 2, which corresponds to 100 ppm of Cyadox and 100 ppm of tylosin per 1 kg of feed mixture.

Medicated piglets were calmer, more adaptable, and better tolerated temperature fluctuations in the barn. No diarrhea or other diseases were observed. In control piglets, diarrhea occurred from

On the 2nd day after housing, diarrhea occurred in 20 to 30% of the animals, and from the 8th to the 12th day, diarrhea was sporadic. Diarrhea-prone piglets were treated with Carbo medicinalis + Celaskon pulv.

The good health of piglets treated with the test product was reflected in increased weight gain and improved feed conversion, as can be seen from Table No. 4.

Table No. 4

Group Tentative Control Duration of the experiment 20 days 20 days Dose of substances in feed Cyadox 100 ppm Tylosin 100 ppm - Initial weight x in kg 6.10 5.96 Final weight x in kg 14.03 10.98 Daily gain x in kg 0.400 0.250 Index x of the increase in % 160.0 100.0 Feed conversion in kg 1.79 2.13 Index in % 84.04 100.0

Example 5

In the fattening plant, a stationary occurrence of bloody diarrhea is observed in about 5 to 10% of the animals. These are pre-fattening pigs of the BU x PC x L breed weighing about 40 kg, housed in pens of about 15 pigs. The diagnosis of the disease was determined on the basis of pathological-anatomical, bacteriological and bacterioscopic examination. Vibrio coli was found to be the causative agent of the diarrheal disease.

Organization of the experiment: Pigs were divided into two groups, control 38 animals, experimental 31 animals and fed with a SOL mixture, to which in the experimental group was added 1% by weight of the tested preparation in the form of a premix containing 1% by weight of Cyadox and 1% by weight of sulfadimidine. The tested preparation was administered for 21 days.

No further bloody diarrhea was observed in the experimental group, the tested preparation was 100% effective. In the control group, bloody diarrhea was observed in 5 to 10% of the animals throughout the entire period. At the end of the experiment, one pig was sent for mandatory slaughter due to its very poor health.

I

The good health of the treated animals was reflected in the performance indicators shown in Table 5.

Table No. 5

Group

Experimental

Control

Duration of the experiment

Dose of substances in feed

Initial weight x in kg Final weight x in kg Total gain x in kg Daily gain x in kg Gain index x in % Feed conversion in kg

Index in % of days

Cyadox 100 ppm Sulfadimidine 100 ppm

38.52

55.13

16.61

0.790

143.64

3.34

80.87 days

41.71

53.21

11.50

AND

0.550

100.0

4.13

100.0

Example 6

In a large-scale pig farm, bloody diarrhea and bronchopneumonia were observed in 10 to 20% of pigs. These were pre-fattening pigs weighing about 50 kg housed in pens. The diagnosis of the disease was determined on the basis of pathological-anatomical, bacteriological and bacterioscopic examination. Treponema hyodysenteriae and Vibrio coli were found to be the causative agents of the diarrheal disease.

Organization of the experiment: Pigs were divided into a control group - 45 pigs and an experimental group - 40 pigs. The tested preparation was mixed into the experimental group in the form of premixes in the mixture for fattening pigs SOL and was administered for 17 days.

In the experimental group, bloody diarrhea disappeared within 3 days. In the control group, diarrhea occurred during the experiment, bloody in some pigs. 1 pig from the control group died during the experiment (day 14).

The therapeutic effect of the tested product was reflected in objective performance indicators, i.e. in weight gain and feed conversion, as can be seen from Table 6.

Table No. 6

Group Tentative Control Duration of the experiment 17 days 17 days Dose of substances in feed Cyadox 100 ppm Phthalazole 100 ppm - Initial weight x in kg 61.03 58.98 Final weight x in kg 72.78 66.32 Total gain x in kg 11.75 7.34 Daily gain x in kg 0.690 0.430 Index x of the increase in % 160.47 100 _A 0

Continuation of table no. 6

Group Tentative Control Feed conversion in kg 3.35 3.87 Index in % 86.56 100.0

Explanation of abbreviations of the feed mixtures used:

COS 1 (% by weight)

fish meal 6 skimmed milk powder 30 to 36 extracted soybean meal 16 to 20 flaxseed 5 wheat germ 3 oatmeal (rice) 5 to 13 potato flakes 6 to 10 sugar 5 dicalcium phosphate 0.5 biofactor supplement 1 mineral feed additive III 0.5 barley 9 to 15 100, What 2 (% by weight) fish meal 6 to 10 skimmed milk powder 5 to 10 extracted soybean meal 14 to 19 corn 0 to 20 wheat 10 to 30 barley 12 to 25 wheat flour for feed 5 to 10 oatmeal 0 to 10 cereal ₍ sprouts) 0 to 4 potato flakes 0 to 10 sugar 3 feed salt 0.2 dicalcium phosphate 0.5 biofactor supplement 1 mineral feed additive III 0.5 whey powder 0.4 100 SOL (% by weight) extracted soybean meal 3 to 6 wheat 15 to 40 barley 20 to 60 corn 0 to 30 oats 0 to 10 rye 0 to 5 feed legumes 0 to 3 meat and bone meal or poultry meal or wine lees .0 to 3

microbial protein or sulfite yeast or potato protein 0 to 3 mineral and vitamin concentrate SOL 2 bran 0 to 10

100

Biofactor supplement for ČOS type feed mixtures:

vitamins A, D ₂ , C and E, essential amino acid lysine, antioxidant stabilizer (Curasan).

Biofactor supplement for SOL feed mixtures:

vitamin D ₂ , essential amino acid lysine, antioxidant stabilizer.

Mineral feed additive - MKP III - for feed mixtures of the ČOS type:

% by weight of calcium carbonate and trace element salts.

Mineral and vitamin concentrate for SOL type feed mixtures - MVK SOL:

(% by weight)

MD I 1.5 wheat feed flour 8.5 feed salt 15.0 feed limestone 50.0 biofactor supplement SOL 25.0

100

Mineral supplement - MD I:

sulfate copper 80 000 mg sulfate ferrous 400 000 mg oxide ; cyanide 200 000 mg manganese carbonate 100 000 mg iodide potassium 1 000 mg sulfate cobalt 100 mg sulfate calcium 50 500 mg feed flour 1,000 000 mg

Claims (2)

PREVENTION OF THE INVENTION A composition for the treatment of feedstuffs for livestock with a growth-stimulating effect, comprising, in addition to carriers and / or excipients, optionally other additives, characterized in that it contains 2-formylquinoxaline-1,4-dioxide cyanacetylhydrazone in combination with tylosin as active ingredients or a sulfonamide, wherein their weight ratio to each other is from 10: 1 to 1:10. 2. A composition according to claim 1 wherein the sulfonamide is 2- (N-phthalylsulfanilylamino) thiazole or 4,6-dimethyl-2-sulfanilamidopyrimidine.