AU2011241442A1

AU2011241442A1 - Animal feed additive having an antimicrobial and growth-promoting effect

Info

Publication number: AU2011241442A1
Application number: AU2011241442A
Authority: AU
Inventors: Klaus Neufeld
Original assignee: Individual
Current assignee: Individual
Priority date: 2010-04-15
Filing date: 2011-03-24
Publication date: 2012-11-08
Anticipated expiration: 2031-03-24
Also published as: EP2557941B1; AT509728B1; EP2557941A1; BR112012026367B8; BR112012026367B1; BR112012026367A2; KR20130052562A; WO2011127496A1; KR101889859B1; ES2536249T3; AT509728A1; DK2557941T3; AU2011241442B2

Abstract

The invention relates to an animal feed additive having an antimicrobial, growth-promoting, and appetite-stimulating effect, characterized in that the animal feed additive contains a plant extract or plant material, which contains one or more alkaloids, in combination with an extract or material from plants of the Magnolia genus.

Description

WO 2011/127496 Al ANIMAL FEED ADDITIVE HAVING AN ANTIMICROBIAL AND GROWTH-PROMOTING EFFECT The invention relates to an animal feed additive having an antimicrobial, growth-promoting and appetite stimulating effect, use thereof, and a method for promoting growth and stimulating appetite in livestock. "Growth-promoting agents" have been used worldwide in livestock feed over a long period of time. The main group of growth-promoting agents were antibiotic and chemical growth-promoting agents, such as zinc bacitracin, flavophospholipol, virginiamycin, tylosin phosphate, avoparcin, olaquindox and monesin sodium, which were also permitted in Austria as growth promoting feed additives. "Probiotics" or microbiological growth-promoting agents have also been used for a number of years now. The purpose of all growth-promoting agents is to increase the intensity of growth of livestock. Antibiotic and chemical growth-promoting agents have fallen into disrepute in recent years, however, particularly among consumers, and were banned as feed additives in 2006 throughout the European Union. Internationally, the use of antibiotic and chemical growth-promoting agents has become restricted or is now banned. Microbiological growth-promoting agents (probiotics) have been developed with the objective of ensuring economical animal production and, at the same time, of corresponding to the consumer demand for natural animal nutrition. However, probiotics do not entirely meet the economical expectations of modern farming, which is impelled to provide an efficient production process.

- 2 Plant substances having antimicrobial properties have also become established in many countries in animal production. Not least, because in numerous countries the use of chemical and antibiotic growth-promoting agents has been banned. Due to the plant origin, costly extraction methods and volatility of some of these products, many of these substances are not viable for use in farming from the point of view of an economical production process. Patent numbers AT 403873B, EP 0581926B1, EP 1317187B1 and EP 1317188B1 describe such plant growth-promoting agents based on isoquinoline alkaloids. These products have become widespread in recent years throughout the world. Due to the development in agricultural production and a continuous increase in feed prices however, it is necessary to provide these products so that they are more economical for the market and are more efficient in terms of the effect they produce. The invention will provide a solution to this. In accordance with the invention, an animal feed additive having an antimicrobial, growth-promoting and appetite-stimulating effect is proposed and is characterised in that it contains an alkaloid containing plant extract or plant material in combination with an extract or material from plants of the Magnolia genus. The expression "plant material" includes both the whole dried plant and parts thereof, such as leaves, flowers, fruits, roots, rhizomes or the bark. These substances are used predominantly in pulverulent or granulated form. It is also freely possible to extract the plant material so as to then use the liquid extract itself or the vaporised extract.

- 3 The active ingredient components used in accordance with the invention cause a synergy effect in terms of the antimicrobial action with simultaneous growth promotion and/or appetite stimulation of the control animals examined. This synergy effect is to be attributed to the interaction of the alkaloids, in particular isoquinoline alkaloids, with the active ingredients from the Magnolia, such as Magnolol and Honokiol. Further advantageous embodiments of the animal feed additive according to the invention are disclosed in accordance with dependent Claims 2 to 11. The invention further relates to an animal feed that is characterised in that the animal feed additive according to the invention is present in an amount from 0.001 g/t to 10 kg/t of feed. The invention further relates to a method for promoting growth and/or stimulating appetite in livestock, said method being characterised in that the livestock are fed the animal feed according to the invention, which contains the animal feed additive according to the invention in an amount from 0.0001 mg to 350 mg per kg of live weight per day. The invention further relates to the use of the animal feed additive according to the invention for the treatment or preventative treatment of animals against pathogenic microbes. The invention will now be explained in greater detail on the basis of experiments and comparative series of tests.

-4 In an in vitro experiment, it was possible to demonstrate by means of the plate inhibitor test that a combination of a plant extract from Macleaya cordata and a plant extract from Magnolia spp., such as Magnolia acuminata, Magnolia biondii, Magnolia denudata, Magnolia grandiflora, Magnolia kobus, Magnolia obovata, Magnolia officinalis, Magnolia sprengeri, Magnolia tripetala, Magnolia virginiana or Magnolia glauca, in a ratio of 1:1 led to a considerable improvement of the inhibitory effect with respect to Staphylococcus aureus than is the case with the same amount by weight of an extract from Macleaya cordata or an extract from Magnolia spp. To carry out these series of tests, the active ingredients of Macleaya cordata are preferably obtained by extraction from the fruits thereof. The fruits are dried at 50 0C to a dry substance content of at least 91 % and are then ground. The powder thus obtained is extracted in a percolator at a temperature of 100 *C with 0.1 molar hydrochloric acid solution as extraction agent. The extract is then vaporised, taken up in ethanol and set to the desired active ingredient content. The active ingredients from Magnolia officinalis are preferably obtained from the bark by means of supercritical C02 extraction. The raw material is washed and dried at 50 0C to a dry substance content of at least 91 % and then size-reduced. In the extractor, the raw material thus prepared is extracted with supercritical C02 as extraction agent at a flow rate of 1,200 to 1,400 litres per hour for a period of 3.5 hours at a pressure of 25 to 30 MPa and a temperature from 35 to 40 *C. The C02 extract is then taken up in ethanol and set to the desired active substance content.

- 5 An exemplary amount of 25 to 50 mg of obtained animal feed additive according to the invention now has a Sanguinarine content of 1.5 % and can be mixed into a conventional animal feed. It is also possible, however, to provide the animal feed additive according to the invention with an active ingredient content lower than 1.5 % if the active ingredients are obtained from non extracted plant material, for example dried leaves of Macleaya cordata. In such cases, the dosing must be much higher however. On the other hand, what are known as "pre-mixes" and "feed supplements" are also included under the term "feed". Pre-mixes and feed supplements are feed concentrates that are mixed with other feed components so as to produce a final, prepared feed. Pre-mixes and feed supplements therefore contain the animal feed additive according to the invention in a much higher concentration since they are intended to be diluted to a considerable extent. A dosing of 10 kg/t can thus be set. A low dosing of 1 mg/t is set for example if the animal feed additive according to the invention is an extract with a high active ingredient content. In the in vitro test below, feeds that contained the active ingredient combination of Macleaya cordata and Magnolia spp. in a ratio of 1:1 were tested. The specific measured values with regard to this in vitro test were as follows: Active Macleaya Magnolia Macleaya ingredient cordata spp. cordata + extracts Magnolia spp. 1:1 Breadth of 6 mm 5 mm 8-10 mm the zone of -6 inhibition Bacteria Staphylococcus aureus Within the scope of various feed experiments, a considerable improvement in the promotion of growth could be obtained with a combination of an extract of Macleaya cordata and an extract of Magnolia spp. compared to a conventional feed additive produced from Macleaya cordata alone or Magnolia spp. alone. Table 1 Control Macleaya Macleaya group cordata cordata + Magnolia spp. 1:1 Mix-in rate of the - 30 ppm 30 ppm animal feed additive Number of fattened 80 80 80 pigs Experimental period 30-100 kg 0 daily increase (g) 831 868 880 Weight range 30-100 kg 0 daily increase (g) 775 788 801 Weight range 30-53 kg 0 daily increase (g) 868 914 925 Weight range 53-100 kg 0 daily feed intake 2.30 2.33 2.33 (kg) Weight range 30-100 kg 0 daily feed intake 2.57 2.66 2.68 (kg) Weight range 30-100 kg -7 Feed efficiency 30- 2.76 2.69 2.65 100 kg Feed efficiency 30-53 2.28 2.22 2.20 kg Feed efficiency 53- 2.99 2.91 2.90 100 kg Lean meat proportion 59.5 59.9 60.0 It can be seen from the values listed in Table 1 that a lower daily increase in weight (lower by 12 g on average) was observed over the entire fattening period when a material obtained exclusively from Macleaya cordata or extracted from this plant was fed compared to an embodiment of the animal feed additive according to the invention produced from Macleaya cordata and Magnolia spp. in a ratio of 1:1. It is also clear from table 1 that feed intake is increased in all fattening ranges compared to the control group. High-performing fattened pigs with average daily increases of more than 830 g (even in the control group with no growth-promoting feed additive!) are peak performers with extreme feed intake. In these performance ranges, any further increase is to be considered a success. Table 2 Control Magnolia Macleaya group spp. cordata + Magnolia spp. 1:1 Mix-in rate of the - 50 ppm 50 ppm animal feed additive Number of fattened 48 47 50 pigs Experimental period 30-100 kg 0 daily increase (g) 798 819 846 Weight range 30-100 kg 0 daily feed intake 2.24 2.28 2.32 (kg) Weight range 30-100 kg Feed efficiency 30-100 2.81 2.78 2.74 kg With exclusive feeding of extracts and materials produced from Magnolia spp., a lower daily increase in weight (lower by 27 g) was achieved compared to that observed with the animal feed additive according to the invention. In this experiment with the animal feed additive according to the invention, a daily feed intake that was 80 g higher compared to the control group was recorded. Similar values were achieved over the course of series of tests concerning examination of the increase in weight of piglets; see the values from Tables 3 and 4. Table 3 Control Macleaya Macleaya group cordata cordata + Magnolia spp. 1:1 Mix-in rate of the - 25 ppm 25 ppm animal feed additive Number of piglets 49 49 49 Experimental period 40-60 days (age) Rearing phase 12-32 days after weaning 0 body weight at the 13.5 13.2 13.2 start of the experiment (kg) -9 0 body weight at the 25.6 25.7 26.0 end of the experiment (kg) 0 daily increase (g) 607 624 640 0 daily feed intake (g) 895 902 907 Feed efficiency (kg 1.47 1.45 1.42 feed intake/kg increase) Table 4 Control Magnolia Macleaya group spp. cordata + Magnolia spp. 1:1 Mix-in rate of the - 25 ppm 25 ppm animal feed additive Number of piglets 49 49 49 Experimental period 40-60 days (age) Rearing phase 12-32 days after weaning 0 body weight at the 13.1 13.3 13.2 start of the experiment (kg) 0 body weight at the 25.4 26.1 26.2 end of the experiment (kg) 0 daily increase (g) 615 640 650 0 daily feed intake (g) 916 928 922 Feed efficiency (kg 1.49 1.45 1.42 feed intake/kg increase) In all experiments conducted, the feed intake was thus increased compared to the control group. A comparison with those experiment groups supplied with other feed additives likewise known as appetite stimulants was - 10 also predominantly positive. In this regard it can be noted that it is quite normal, within the range of feeding experiments, that not all effects of an additive can be measured to the same extent in all experiments carried out, and that clear biological fluctuations may be observed. Where the animal feed additive according to the invention was fed, not only could an improvement in weight increase above the values of conventionally known growth-promoting agents be observed, but also an improvement in the state of health, which is reflected in a lower loss rate due to disease. Necrotising enteritis, triggered by Clostridium perfringens, poses a big economical problem in birds specifically, particularly in laying hens. The symptoms are chronic enteritis, reduced feed intake, increased water intake, sloppy droppings, changes to plumage, feather pecking and feather eating, weight loss, reduced laying performance with an increased variance in egg weight, reduced working life, susceptibility to infection and increased mortality due to exhaustion or secondary infections, such as E. coli infections. The disease has proven to be protracted and resistant to treatment. The administration of antibiotics is problematic, since the symptoms of the disease recur once treatment is stopped and treatment with antibiotics causes high economical damage due to the withdrawal periods. Eggs cannot be used during treatment and during the withdrawal period, and broilers (fattened chickens) cannot be treated due to the short fattening period thereof. Other possible treatment options, such as changing the feed composition, adapting the raw fibre content or raw protein content in the feed, administering essential - 11 amino acids or fatty acids, adapting the vitamin content or mineral content in the feed, adding organic acids, etc. have proven to be inefficient. In egg-producing farms in which the above-described symptoms have already been observed in various flocks for more than two years, a newly diseased flock was administered the substance according to the invention in a dosing of 100 ppm (100 g per tonne of feed) approximately five weeks after appearance of the first symptoms. A lasting improvement was obtained, the flock was completely free from symptoms and economical egg laying could thus be continued. The following experiments listed in Table 5 show these results. The feed additive according to the invention was also tested compared to known antibiotic growth promoting agents. Table 5 Antibiotic Macleaya Macleaya growth- cordata cordata + promoting Magnolia agent spp. 1:1 Mix-in rate of 15 ppm 50 ppm 30 ppm the animal feed additive Number of 89,500 89,500 90,100 broilers Experimental 36 36 36 period (days) 0 daily increase 43.2 43.6 43.5 (g) Feed efficiency 1.81 1.78 1.78 Losses (% of 7.4 4.2 3.9 broilers) - 12 Table 6 Antibiotic Magnolia Macleaya growth- spp. cordata + promoting Magnolia agent spp. 1:1 Mix-in rate of 15 ppm 50 ppm 30 ppm the animal feed additive Number of 43,200 41,500 42,000 broilers Experimental 35 35 35 period (days) 0 daily increase 44.1 43.8 44.3 (g) Feed efficiency 1.79 1.83 1.81 Losses (% of 5.8 4.9 3.8 broilers) It can thus be seen from the values shown in the tables that losses of 7.4 % were still observed with antibiotic growth-promoting agents known per se. Although an additional reduction in losses is obtained when feeding Macleaya cordata, a further reduction in losses, as shown in Tables 5 and 6, could undoubtedly be attributed to the combined effect of Macleaya cordata and Magnolia spp. Similar results were also observed in egg-laying livestock in terms of the number of eggs laid, classification quality of the eggs, feed efficiency and animal losses. The same effect was also noted in fish in terms of growth intensity, feed intake and loss. Similar positive results were observed in weaned piglets and fattened pigs.

- 13 The diarrhoeal diseases of dysentery, triggered by Brachyspira hyodysenteriae, as well as PIA (porcine intestinal adenomatose), triggered by Lawsonia intracellularis, often occur frequently in weaned piglets and fattened pigs. These diseases are characterised by diarrhoea with grey and watery droppings. The economical damage of these diseases lies in the additional expenditure for treatment, reduced feed intake, poor growth, susceptibility to secondary diseases and increased mortality. Antibiotic medication in the feed for a period of three to four weeks with a hygiene programme running in parallel is a suitable treatment method. Regular antibiotic treatment of this type is viewed with scepticism from a veterinary and epidemiological point of view due to the known problems concerning resistance. This means a considerable cost outlay for farms. In many farms encountering problems with frequent occurrence of dysentery and PIA, a lasting improvement in the symptoms of the disease and a significant reduction in losses (mortality) could be achieved with the animal feed additive according to the invention in a dosing of 60 ppm (60 g per tonne of prepared feed). It could therefore be proven that a new antimicrobially effective substance combination with particularly favourable properties in the field of animal production has been developed using a combination of plant material or extracts of the two plant species Macleaya and Magnolia.

Claims

1. An animal feed additive having an antimicrobial, growth-promoting and appetite-stimulating effect, characterised in that it contains an alkaloid containing plant extract or plant material in combination with an extract or material from plants of the Magnolia genus.

2. The animal feed additive according to Claim 1, characterised in that the extract or material from plants of the Magnolia genus contains Magnolol and/or Honokiol.

3. The animal feed additive according to Claim 1 or 2, characterised in that the alkaloid-containing plant extract or plant material is obtained from plants of the Macleaya and/or Sanguinaria Canadensis genus.

4. The animal feed additive according to one of Claims 1 to 3, characterised in that the alkaloid containing plant extract or plant material is obtained from poppy seeds.

5. The animal feed additive according to one of Claims 1 to 4, characterised in that the alkaloid containing plant extract or plant material is obtained from barberries.

6. The animal feed additive according to one of Claims 1 to 5, characterised in that the alkaloid containing plant extract or plant material contains Sanguinarin and/or Chelerythrin.

7. The animal feed additive according to one of Claims 1 to 6, characterised in that the extract -2 or material is obtained from plants of the Magnolia genus, namely from Magnolia officinalis.

8. The animal feed additive according to one of Claims 1 to 7, characterised in that the extract or plant material is obtained from plants of the Magnolia genus, namely from Magnolia spp., such as Magnolia acuminata, Magnolia biondii, Magnolia denudata, Magnolia grandiflora, Magnolia kobus, Magnolia obovata, Magnolia officinalis, Magnolia sprengeri, Magnolia tripetala, Magnolia virginiana or Magnolia glauca.

9. The animal feed additive according to one of Claims 1 to 8, characterised in that it contains extracts or materials of Macleaya cordata and of Magnolia spp. in equal proportions.

10. The animal feed additive according to one of Claims 1 to 9, characterised in that it contains extracts or materials of Macleaya cordata and Magnolia spp. in proportions of 1:100 to 100:1.

11. The animal feed additive according to one of Claims 1 to 10, characterised in that it contains extracts or plant material with a content of Sanguinarin and/or Chelerythrin in proportions of 1:100 to 100:1 as well as an extract or plant material with a content of Magnolol or Honokiol or a mixture of Magnolol and Honokiol in a ratio from 20:1 to 1:20.

12. An animal feed comprising an animal feed additive according to one of Claims 1 to 11, characterised in that the animal feed additive is present in an amount from 0.001 g/t to 10 kg/t of feed. -3

13. A method for promoting growth and/or stimulating appetite in livestock, characterised in that the livestock are fed an animal feed according to Claim 12, which contains an animal feed additive according to one of claims 1 to 11 in an amount from 0.0001 mg to 350 mg per kg of live weight per day.

14. Use of the animal feed additive according to one of claims 1 to 11 for the treatment or preventative treatment of animals against pathogenic microbes.

15. Use of the animal feed additive according to one of claims 1 to 11 for the treatment of diarrhoeal diseases, in particular such as dysentery and porcine intestinal adenomatose (PIA).

16. Use of the animal feed additive according to one of claims 1 to 11 for the treatment of necrotising enteritis.