WO2004110425A1 - Use of sorbic aid for prevention of bacterial infections and as performance enhancer for animals - Google Patents

Abstract

Sorbic acid and the salts thereof, of example, K Mg or Ca sorbate are suitable for the prophylaxis and therapy of bacterial infections, in particular, Campylobacter or Salmonella infections in domesticated or domestic animals. Said substances are added to the drinking water or the feed of the animals in concentration of preferably 0.1 to 8 wt.%.

Description

Use of sorbic acid to prevent bacterial infections and as a performance enhancer in animals

The invention relates to the use of sorbic acid and / or its salts to avoid bacterial infections and as a performance enhancer in animals. For this purpose, sorbic acid and / or its salts or mixtures of these substances are preferably added to the drinking water or feed of the animals. Potassium sorbate, magnesium sorbate or calcium sorbate are preferably used as salts. The preparations are preferably used in the rearing of young animals.

Different types of feed enable the growth of various microorganisms. Of these, yeasts and molds are of primary importance as sources for their spoilage and the formation of mycotoxins. They can also affect the digestion of the animals and thus worsen feed conversion and growth. Preservatives such as sorbic acid, propionic acid and formic acid suppress the development of unwanted yeast and mold in feed and thus prevent the adverse effects of these groups of microorganisms. A sufficient antibacterial effect of these substances has not yet been found or described.

In feed with a higher water content, however, bacteria can reproduce and at least survive with a lower water content. If such bacteria get into the animal body, there is the possibility that they multiply there and either lead to animal diseases and losses in animal fattening or even pass to the meat obtained from the animals and meat products made from them.

Industrial production of the feed, longer transport routes and longer storage times in the animal fattening farms have led to a significant increase in the possibilities for the growth of microorganisms in feed. As a result, animal feed has increasingly become a source of contamination for the animals and the products or foods made from them. Protection against bacterial spoilage with the help of preservatives has so far not been satisfactorily possible even with food. There are more favorable starting conditions for the preservation of food than for animal feed. In food production, it is easier to avoid contamination of raw materials and intermediate products, since it is easier to maintain hygienic framework conditions during production and storage, which means that there is already a much lower bacterial load from the outset. If satisfactory protection cannot be achieved with the approved preservatives, the generally more complex and expensive physical methods of preservation such as sterilizing canned goods, pasteurizing products with a limited shelf life or deep-freezing can be used.

Bacterial spoilage of feed can not only have adverse effects on the animals, but can even lead to contamination of slaughtered meat with pathogenic germs. In addition to a health hazard for the consumer, there are also considerable economic losses in livestock breeding with regard to the growth of the animals.

Such bacterial spoilage is much more likely than in animal feed that is contaminated with considerable amounts of microorganisms at the raw material stage and under many conditions that are common in their production and can favor the growth of microorganisms for the reasons mentioned in food. So find z. For example, many microorganisms generally have good opportunities for reproduction at the temperatures prevailing in the stables. If there is a high level of initial contamination, this can increase to bacterial counts even with the feed standing for a limited period, which can be recognized as obvious spoilage.

The possibilities of contamination increase even further under the conditions of the feed preparation, which in practice are often in the barn or near the

Stalls, i.e. an environment with a high risk of contamination. This also applies to feed with a higher water content, which is often only shortly before feeding be prepared.

Another significant risk is the so-called cross-contamination. This means the contamination of animal feed by faeces of useful or domestic animals infected with pathogenic germs. This problem, which occurs particularly in free-range husbandry and inadequate stall hygiene, can build up into a self-reinforcing cycle in such a way that the animal intestine contributes to the continuous multiplication of the germs, which is continually newly contaminated via the path faeces → feed - »intestine.

Infections with Campylobacter and Salmonella in particular are becoming increasingly important in the practice of animal husbandry, although the incidence for Campylobacter infections is now higher in some federal states than for Salmonella infections.

In order to prevent contagion of animals with Campylobacter and Salmonella, it is important to avoid or reduce the contagion with the pathogen. Sufficient cleaning of the direct animal environment, e.g. B. cages, with subsequent disinfection and repeated cleaning. Other measures such as regularly changing the bedding and boiling out the drinking and feeding vessels at temperatures in the range above 80 ^° C. are also very important for prevention. The environment of the animals should be kept clean and hygienic.

Despite these sometimes very complex measures, Campylobacter and Salmonella are infested with a wide variety of animals, leading to high economic losses in animal fattening. The areas where many young animals are kept close together are of particular economic importance. An infection can spread there within a short time.

In order to contain such infections, prophylactic treatment is generally practiced in animal husbandry. The aim is to prevent clinically manifested illnesses, considerable loss of performance (reduced Growth of animals) in animal fattening or total failures of entire groups / herds. For this, antibiotics such as B. decoquinate, amprolium, halofuginone C ⁹ HALOCUR) ₁ monensin (Rumensin ^®) or Toltrazuril ^(® Baycox) added to the feed over a period of 1 to 3 weeks or administered parenterally. However, the use of antibiotics in this area is suspected of being responsible for dangers that arise from resistant bacteria and can also endanger human health in the long term.

For this reason, the professional community is looking for health-less safe means for this purpose. In other areas, too, physiologically and epidemiologically harmful substances that are sometimes not harmless to the environment, such as antibiotics, formaldehyde-releasing substances, halogenated compounds and other z. B. in food and feed for useful or domestic animals replaced by less hazardous substances. The purpose for which these substances are used is primarily to preserve the value of the actual animal feed. In addition, however, its hygienic condition should also be improved or an extended shelf life should be achieved.

Furthermore, in order to comply with the now stricter legal provisions after the use of such agents, in particular after the use of antibiotics, increasingly longer waiting times have to be observed before the animals are slaughtered in order to be able to offer the consumer food that is harmless to health.

The object of the present invention was therefore to provide an anti-infection agent or substances with which bacterial infections, in particular those with Campylobacter and Salmonella, are suppressed in animals or with which the occurrence of such infections can be avoided from the start. This agent or these substances should be harmless to health and easy to handle. Furthermore, they should be easy to process or handle in agriculture, for example as a drinking water or feed additive, and none -Q-

have an adverse impact on the environment. Ultimately, these agents / substances should be particularly suitable for interrupting the contamination cycle via feed contaminated with contaminated faeces.

This object is achieved by the use of sorbic acid and / or its salts or a mixture of these substances for producing an anti-infectious agent or as a feed additive for preventing bacterial infections, in particular Campylobacter or Salmonella infections, in animals and for the treatment of farm animals or pets who are infected with these infections. Since the use of the substances / agents mentioned in the animal fattening has a positive influence on the growth of the animals, also due to the avoidance of infectious diseases, these substances / agents thus also represent so-called performance promoters for useful animals and pets.

Sorbic acid is often used to preserve animal feed. Sorbic acid (= trans, trans-2,4-hexadienoic acid) is a colorless, solid compound that dissolves only slightly in cold water and is used worldwide as a preservative, mainly in food. Sorbic acid and its salts have a very good microbiostatic, antifungal effect. An effect against parasites has not been described so far.

Surprisingly, however, it was found that the administration of sorbic acid and / or its salts enables effective prophylaxis against infection with Campylobacter and Salmonella. In particular under housing conditions that pose an increased risk of cross-contamination of the feed by infected faeces, feed / drinking water enriched with sorbic acid or its salts can be used effectively to break through a self-reinforcing contamination cycle through Campylobacter and Salmonella.

Sorbic acid and / or its salts or mixtures of these substances are preferred without further formulation aids in solid or powder form directly Feed and / or the drinking water of the animals added. In addition, the substances mentioned can also be in any other dosage form / formulation which is customary in animal husbandry or veterinary medicine, such as. B. solutions, emulsions, tablets. The formulation of the substances presents no difficulties and applicable formulation auxiliaries and additives are known to the person skilled in the art. Furthermore, the substances can also be added to the feed as a so-called (feed) premix.

Sorbic acid or its salts can be administered alone or in conjunction with therapy in combination with other antimicrobial substances for this purpose. In addition to common antibiotics and short-chain organic acids such as formic, acetic, propionic and butyric acids, these also include citric acid,

Malic, fumaric or maleic acid, bactericidal enzymes such as. B. lysozymes, oxidases,

Peroxidase or phospholipases and polyunsaturated fatty acids (PUFAs), especially the omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA

(Docosahexaenoic acid) as well as the omega-6 fatty acid ARA (arachidonic acid) as well as oils and triglycerides, which contain these PUFAs.

The combinations of sorbic acid and its salts with one or more of the above-mentioned substances can, depending on the physical state of the other antimicrobially active substances, be prepared in all powder mixtures, solutions, emulsions or suspensions known to the person skilled in the art or in the form of tablets, extrudates or pallets Feed or drinking water can be added together or separately, the sorbic acid or its salts also serving as a carrier of a liquid component. Preferred concentration ranges for the short-chain organic acids are in the range from 0.5 to 40 g / kg of drinking water or feed, but particularly preferably from 1 to 20 g / kg. A preferred concentration range for PUFAs in combination with sorbic acid and its salts is 0.1 mg to 20 g / kg of feed or drinking water, preferably 0.1 mg to 5 g / kg.

The preparations according to the invention are used in farm animals, for. B. at the -J-

Poultry keeping, in mammals such as cattle, pigs, sheep and rodents, preferably rabbits, and in the keeping of pets, preferably dogs, cats and birds. They are used to prevent bacterial infections, in particular Campylobacter and Salmonella infections, in animals and to treat farm animals or pets infected with these infections.

The agents / substances according to the invention are preferably used in those cases in which the risk of cross-contamination of the feed after application is particularly high due to the conditions in the barn or keeping, such as in broilers' free-range or free-range keeping. They not only protect the feed from bacterial infestation, they also act in the intestines of the animals and support the formation of a native, non-pathogenic microflora.

In addition to sorbic acid, potassium sorbate, magnesium sorbate, ammonium sorbate or calcium sorbate are preferably used as salts according to the invention.

Free sorbic acid is preferably added to the feed of livestock and domestic animals, while its salts are more suitable as an additive in drinking water. The amount of sorbic acid or its salts which is suitable for reliably preventing infection, in particular with Campylobacter or Salmonella, or for acting as a performance enhancer, is preferably in the range from 1 to 50 g / kg of drinking water or feed, particularly preferably in the range from 5 to 40 g / kg of drinking water or feed, while the amount of sorbic acid or its salts required to contain or eliminate an existing Campylobacter and Salmonella infection is higher and preferably in the range of 5 to 80 g / kg of drinking water or Animal feed, particularly preferably in the range from 10 to 60 g / kg.

The indication g / kg of feed in the given widths is universal for the relevant animal species. The duration of administration is e.g. B. for: prophylaxis for broilers: subject to possible waiting times ^" before slaughter always during the rearing period (27 to 60 days, with ecological keeping 80 days), with therapy accompanying therapy to the point of absence of symptoms;

Prophylaxis in pigs: subject to possible waiting times, always during the rearing period (approx. 6 months), otherwise until there are no symptoms.

According to the invention, particular preference is given to the use of sorbic acid and / or its salts for preventing infections with Campylobacter and Salmonella in the rearing of young animals and in the keeping of laying hens.

The invention is explained in more detail below with the aid of examples.

Examples: Determination of the germ-reducing activity against Salmonella Typhimurium and Campylobacter jθjuni

Prüfunαsbedinαunαen

Product name: Potassium sorbate Nutrinova (E202) granules, 500 g

Lot No .: 10928

Appearance of the products: white granules

Storage conditions: room temperature Test organisms: Salmonella Typhimurium, DSM 554 L + S-Ch .: R23-080311

Campylobacter jejuni, DSM 4688 L + S-Ch .: F107-129771

Germ load: 10 ² and 10 ⁴ CFU / ml

Test concentrations: 0%, 0.2% and 2.0% sorbic acid corresponding to 0%,

0.268% and 2.68% potassium sorbate exposure times: 0, 24, 48, 72 hours

Counting method: surface method

Incubation conditions: 48 hours, 37 ⁰ C ± 2 ⁰ C

Test method The test substance potassium sorbate (at 0% = no addition) was added to 100 ml peptone water (5 g peptone, 2.5 g yeast extract, 1 g glucose ad 1 liter water; Lot: 16041259) with 10 whey powder (Difco, Lot: 4013760) of potassium sorbate) and the Test batch adjusted to pH 6.0 under sterile cauldrons with 32% HCl. The test batches were inoculated with the test germs at 10 ² and 10 ⁴ CFU / ml and stored in closed glass vessels at room temperature. After the intended exposure times, samples were taken and the number of surviving test germs was determined using a surface spatula method or plate casting method on blood agar plates (BioMerieux, Lot 784873901). All test approaches were carried out in duplicate.

Test results The test germ Salmonella Typhimurium showed in the control batches with 10 ² and 10 ⁴ CFU / ml without addition of sorbic acid a continuous increase in the bacterial count over the examination period of 72 hours. With the addition of 0.2% and 2% sorbic acid, the bacterial count in the batches was reduced by 10 ² and 10 ⁴ CFU / ml over the tested exposure time [cf. Tables 1 to 3 and 1 (bacterial counts of Salmonella typhimurium (incubation with 0.2% sorbic acid) and FIG. 2 (bacterial counts of Salmonella typhimurium (incubation with 2% sorbic acid))].

The test germ Campylobacter jejuni shows in the control batches with 10 ² and 10 ⁴ CFU / ml without addition of sorbic acid a continuous increase in the number of germs over the examination period of 72 hours. With the addition of 0.2% and 2% sorbic acid, the bacterial count in the batches was reduced by 10 ² and 10 ⁴ CFU / ml over the tested exposure time [cf. Tables 4 to 6 and Fig. 3 (Campylobacter jejuni bacterial count (incubation with 0.2% sorbic acid) and Fig. 4 (Campylobacter jejuni bacterial count (incubation with 2% sorbic acid))].

evaluation

In the selected test design. sorbic acid (here: potassium sorbate) in concentrations of 0.2% and 2% is suitable for continuously reducing the number of test germs Salmonella Typhimurium and Campylobacter jejuni over the test period of 72 hours. Table 1: Germ count of Salmonella Typhimurium (incubation with 0% sorbic acid)

Table 2: Germ count of Salmonella Typhimurium (incubation with 0.2% sorbic acid)

Table 3: Germ count of Salmonella Typhimurium (incubation with 2% sorbic acid)

Tabelle 4: Keimzahlen von Campylobacterjejuni (Inkubation mit 0 % Sorbinsäure)

Table 4: Germ count of Campylobacterjejuni (incubation with 0% sorbic acid)

Inoculation with inoculation with 10 ² CFU / ml 10 ⁴ CFU / ml

Exposure time Approach I Approach Il mean Approach I Approach Il mean

Oh 1.1 x 10 ² 1.3 x 10 ² 1.2 x 10 ² 1.7 x 10 ⁴ 1.1 x10 ⁴ 1.4 x 10 ⁴

24 h 7.5 x 10 ² 6.9x10 ² 7.2 x 10 ² 7.3 x 10 ⁴ 1.1 x10 ⁵ 9.2 x 10 ⁴

48 h 2.2 x 10 ³ 8.4x10 ³ 5.3 x 10 ³ 4.3 x 10 ⁶ 2.0x10 ⁶ 3.2 x 10 ⁶

72 h 8.2 x 10 ⁴ 1.2 x 10 ⁵ 1.0x 10 ⁵ 1.1 x 10 ⁷ 1.5 x 10 ⁷ 1.3 x 10 ⁷

Table 5: Bacterial counts of Campylobacterjejuni (incubation with 0.2% sorbic acid)

Table 6: Campylobacterjejuni bacterial counts (incubation with 2% sorbic acid)

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Claims

claims 1. Use of sorbic acid and / or its salts for the production of an anti-infectious agent for the prophylaxis or therapy of bacterial infections in farm animals and pets. 2. Use according to claim 1, characterized in that it is Campylobacter or Salmonella infections. 3. Use according to claim 1 or 2, characterized in that the agent is added to the feed of farm animals and pets. 4. Use according to one or more of claims 1 to 3, characterized in that the agent is added to the drinking water of domestic and domestic animals. 5. Use according to one or more of claims 1 to 4, characterized in that for the prophylaxis of Campylobacter or Salmonella infections sorbic acid and / or its salts 0.1 to 5 wt .-%, based on the feed or drinking water Weight of Food / drinking water can be added. 6. Use according to one or more of claims 1 to 5, characterized in that for the therapy of Campylobacter or Salmonella infections sorbic acid and / or its salts in the feed or Drinking water to 0.5 to 8 wt .-%, based on the weight of the feed / drinking water, are added. 7. Use according to one or more of claims 1 to 6 in the keeping of poultry, in particular laying hens. 8. Use according to one or more of claims 1 to 7 in the Keeping mammals, especially cattle, pigs and sheep. 9. Use according to one or more of claims 1 to 8 in the keeping of rodents, especially rabbits. 10. Use according to one or more of claims 1 to 9 in the keeping of pets, especially dogs, cats and birds. 11. Use according to one or more of claims 1 to 10 in the rearing of young animals. 12. Use of sorbic acid and / or its salts according to one or more of claims 1 to 11. 13. Use of sorbic acid and / or its salts as performance enhancers in farm animals and pets. 14. Use according to claim 13 in an application according to one or more of claims 1 to 11. 15. Means for the prophylaxis and therapy of bacterial infections or for increasing the performance of livestock and pets, containing sorbic acid and / or its salts. * * _* * *