WO2013024067A1 - Use of antioxidants for improving animal health - Google Patents
Use of antioxidants for improving animal health Download PDFInfo
- Publication number
- WO2013024067A1 WO2013024067A1 PCT/EP2012/065806 EP2012065806W WO2013024067A1 WO 2013024067 A1 WO2013024067 A1 WO 2013024067A1 EP 2012065806 W EP2012065806 W EP 2012065806W WO 2013024067 A1 WO2013024067 A1 WO 2013024067A1
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- WO
- WIPO (PCT)
- Prior art keywords
- antioxidants
- cows
- dairy
- antioxidant
- goats
- Prior art date
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
Definitions
- the invention relates to a new use of antioxidants for improving animal health.
- an increase or improvement of the endogenous radical defense system a reduction of inflammatory processes and / or a prevention and / or reduction of fertility problems is achieved by the use of antioxidants and antioxidant substances.
- the need for food has increased worldwide.
- there was an intensification of production especially in the area of meat and milk production.
- the increased number of animals also brings problems. Infections can spread more easily and affect a variety of consumers more quickly.
- prophylactic efforts are made, which focus primarily on the hygiene in the farms.
- Dangerous pathogens of diseases include in particular bacteria. Diseases caused by bacteria and endangering livestock, in particular in the dairy industry e.g. Mastitis, phlegmitis and metritis. These are one of the main causes of losses in the dairy industry.
- antibiotics have been withdrawn in the European Union as prophylaxis in feed.
- mastitis e.g. Antiseptic emulsions or disinfectants are proposed, with which the udder of the dairy cattle is treated.
- an antiseptic composition comprising from 10 to 50% by volume of lemongrass oil.
- a dietary intake of active ingredients would be a simpler and less expensive solution.
- DE 000060217319 T2 proposes the use of a prebiotic which was produced from an oligosaccharide.
- a reduction in inflammatory processes was suggested only by the reduced expression of IL-6 mRNA peripheral blood immunocytes.
- a mixture of at least two antioxidants one of which is a quinoline compound, is added to the feed to prevent oxidation of the fats and lipids contained in the feed, even after feeding to ruminants. It is thought that this could improve the antioxidant status of ruminants.
- Feed additives with antioxidant effects are also known from DE 600 30 253 T2, US Pat. No. 6,156,355, EP 1 392 131 B1, WO 01/58271 A1, WO 2004/091307 A2 and CA 26 183 80 A1.
- the human and veterinary use of antioxidant compositions is further described in DE 696 17 945 T2, DE 60 2004 013 441 T2, WO 2004/1 12776 A2 and WO 2009/108120 A1.
- a prediction of the effect and in particular the effectiveness of antioxidants is not possible, since the effect and effectiveness are not limited to individual oxidation reactions, but are dependent on numerous parameters and complex relationships at the cellular level and even at the animal level.
- Another object of the present invention is to provide substances which are not only used in prophylaxis and act only here, but which can also be used to directly assist in the treatment of diseases and / or problems, in particular fertility problems.
- An additional object of the present invention is the provision of substances which fulfill the abovementioned objects, in particular in ruminants.
- the aim is to reduce oxidative processes that take place in the digestive tract of the animals, so that the oxidative stress for the animal is reduced
- the object is achieved by using antioxidants and antioxidant substances to increase and / or improve the endogenous radical defense system and / or reduce inflammatory processes.
- Another solution is the use of antioxidants to reduce inflammatory processes and / or fertility problems.
- Another solution is the use of antioxidants to help treat inflammatory processes and / or fertility problems.
- antioxidants are used to improve animal health and to increase the endogenous radical defense system and / or to reduce inflammatory processes in such a way that markers for oxidative stress, such as e.g. dROMS (derivatives of reactive oxygen metabolites) and TBARS (
- Thiobarbituric acid reactive substances are reduced in the blood.
- antioxidants in dairy cows in the transit phase and in the phase of high lactation has a positive effect on animal health, preferably on udder health, expressed by a lower cell count (Somatic cell count, SCC) in the milk and by a change in the milk Levels of gene expression of GPX, SOD, catalase and proinflammatory cytokines such as TNF-alpha, interleukin 1 beta or interleukin 6.
- SCC Somatic cell count
- antioxidants for antioxidants as well as for substances with antioxidant effect, where singular and plural of these terms are equivalent.
- Antioxidants in the context of the present invention are substances which bind free radicals and thus prevent their harmful effects.
- Antioxidants can be substances that trap free radicals and block chain reactions. However, they may also be substances with reducing properties, i. Substances that are easily oxidized without forming harmful products. In this case, the antioxidants have a lower redox potential than the substances to be protected. However, antioxidants are also substances which enhance the antioxidant action of others and are included in the group of synergistic antioxidants.
- One embodiment of the present invention relates to the use of antioxidants as well as antioxidant agents for the preparation of an agent for preventing and assisting the treatment of inflammatory processes in animals, preferably selected from the group consisting of mastitis, metritis, laminitis and fertility problems.
- the following embodiments relate to both the use of antioxidants to improve animal health, as well as their use in support of animal health Treatment of inflammatory processes and support of the treatment of fertility problems.
- the following embodiments relate to the use of antioxidants for improving animal health, as well as their use for the preparation of an agent for the prevention of inflammatory processes and prevention of fertility problems.
- the inflammatory processes are mastitis, laminitis, and / or metritis.
- antioxidants are used to reduce fertility problems.
- Fertility problems in the sense of the invention relate to one or more features selected from the following group:
- the animals whose animal health is improved according to the invention are animals selected from the group consisting of farm animals, e.g. Ruminants, non-ruminants, cattle, cows, dairy cows, goats, dairy goats, sheep, dairy sheep, swine, sows, broilers, poultry, parents, chicks, chickens, turkeys, geese, ducks, horses.
- farm animals e.g. Ruminants, non-ruminants, cattle, cows, dairy cows, goats, dairy goats, sheep, dairy sheep, swine, sows, broilers, poultry, parents, chicks, chickens, turkeys, geese, ducks, horses.
- animals selected from the group consisting of ruminants, in particular cattle, cows, dairy cows, goats, dairy goats, sheep and milk sheep, in particular dairy cows.
- antioxidants are used selected from the group consisting of BHT (E 321), BHA (E320), propyl gallate, (E 310), ethoxyquin (E 324), citric acid (E 330), THBQ (319), tocopherols, rosemary extract, and carnitine.
- a combination of antioxidants comprising at least one antioxidant selected from the group consisting of BHT (E 321), BHA (E320), propyl gallate (E310), ethoxyquin (E 324), citric acid (E 330 ), THBQ (E 319), as well as carnitine.
- antioxidant mixture It is particularly preferable to use a combination of these antioxidants as an antioxidant mixture.
- antioxidants alone or in combination with each other or with the o.g. can be used are selected from the group consisting of:
- E220-E228 sulfur dioxide and • E350-E352: malate salts
- E300-E302 E304: ascorbic acid, • E355: adipic acid
- E306-E309 tocopherol and its • E357: potassium adipate
- E310-E312 Gallate •
- E385 calcium disodium ethylene
- E319 tert-butylhydroquinone (TBHQ) diamine tetraacetate (CaNa2EDTA)
- E334-E337 tartaric acid and salts of • N-acetylcysteine
- E338-E343 phosphoric acid and • aminobenzoic acid, dihydroxy salts of phosphoric acid benzoic acid Caffeic acid • gluconic acid
- Flavonoids Flavonoids, flavones and / or • Q10
- Zeaxanthin • lonox for example 100, 300
- a preferred antioxidant mixture contains 5 to 25 wt% BHT (E 321), 1 to 10 wt% propyl gallate (E 310), 1 to 5% ethoxyquin (E 324), 1 to 5% TBHQ and / or 10 to 50% citric acid (E 330).
- the antioxidant mixture contains 10 to 20 wt% BHT, 3 to 8% propyl gallate, 2 to 4% ethoxyquin, 2 to 4% TBHQ, and / or 15 to 40% citric acid.
- a particularly preferred antioxidant mixture contains 17% BHT, 6% propyl gallate, 2%, ethoxyquin, 4% TBHQ and / or 25% citric acid.
- the antioxidant mixture contains 5 to 15% rosemary extract, 5 to 20% natural tocopherol, 1 to 10% TBHQ and / or 1 to 5% BHT, preferably 7.5% rosemary extract, 10% natural tocopherol, 5% TBHQ and / or 3.2% BHT.
- the antioxidant mixture contains 10 to 30% propyl gallate, 1 to 10% BHA (E 320), 1 to 20% citric acid.
- the antioxidant mixture contains 15 to 25% propyl gallate, 5 to 15% BHA and 5 to 15% citric acid, more preferably 20% propyl gallate, 10% BHA and 10% citric acid.
- Antioxidants mixtures liquid A preferred liquid antioxidant mixture contains 1 to 20% by weight of propyl gallate (E 310), 10 to 40% ethoxyquin (E 324), 1 to 25% TBHQ and / or 1 to 15% citric acid (E 330). In a preferred embodiment, the liquid antioxidant mixture contains 1 to 15% by weight of propyl gallate (E 310), 15 to 30% ethoxyquin (E 324), 1 to 20% TBHQ and / or 1 to 10% citric acid (E 330).
- a particularly preferred liquid antioxidant mixture 1 to 10% by weight of propyl gallate (E 310), 20 to 30% ethoxyquin (E 324), 1 to 25% TBHQ and / or 1 to 8% citric acid (E 330), in particular 26, 5% Etoxyquin, 10% TBHQ, 7.5% propyl gallate and / or citric acid 4%.
- the antioxidant mixture contains 1-30% TBHQ, 1-10% propyl gallate and / or 4% citric acid.
- At least 2, 3, 4, 5 or more of the abovementioned antioxidants are preferably used for the antioxidant mixture, preferably 3 or 4, in particular 4.
- ethoxyquin is replaced by THBQ, wherein the antioxidant mixture contains 1 to 20% by weight, preferably 2 to 10% THBQ.
- the antioxidant mixture is used in a proportion of 1 to 1,000 mg per kg of feed TS, preferably 50 to 750 mg per kg, more preferably 75 to 500 mg per kg, in particular 100 to 200 mg per kg of feed TS.
- the antioxidant mixture may also contain the following additional substances: silicates, salts, carbonates, dicalcium phosphates, dextrins, starches, dextrose, fatty acids, vegetable oils, emulsifiers (E490, E484, E432, E433, E434, E435, E436)
- the subject matter of the present invention is furthermore one of the antioxidant mixtures described above.
- the present invention also provides a process for the preparation of one of the antioxidant mixtures described above.
- composition containing antioxidants, the feed, feed or drinking water of the animals is admixed.
- the present invention relates to a method of producing an animal feed comprising the following steps:
- the preparation is carried out in the simplest case by mixing the components.
- the simplest form of mixing is bringing the components together in a mixer.
- Such mixers are known to the person skilled in the art.
- the mixers can be operated discontinuously or continuously.
- the components to be mixed are introduced in the desired ratio and then mixed for a sufficient time in the range of minutes to hours.
- the mixing time and the mixing stress are determined so that the two components are homogeneously distributed in the mixture.
- both components are added continuously, optionally after a premix.
- the residence time and mixing stress should be selected so that both components are homogeneously distributed in the mixture.
- the mixture is usually carried out at room temperature, but can also be carried out at higher or lower temperatures. In a preferred embodiment, the mixtures are carried out at room temperatures.
- the mixture can be carried out at atmospheric pressure, in a vacuum or at elevated pressure.
- mixing at normal pressure is to be preferred.
- the mixture is possible in a mill or over a movement of the entire container. Examples of this are tumble mixers, drum mixers or the like.
- pneumatic mixers Another possibility is the use of pneumatic mixers.
- the mixture of solids is described, for example, in Ullmann's Encyclopedia of Industrial Chemistry, Sixth Edition, 2000, Mixing of Solids.
- the mixtures are optionally prepared at room temperature by combining the components in a mixer and optionally heating to 60 ° C.
- a premix of parts of the mixture is prepared.
- the present invention thus relates to feed additives for animals comprising an antioxidant mixture according to the invention and / or prepared by the process according to the invention and the use of the antioxidants or antioxidant mixture as feed additive or in feed additives or corresponding mixtures of substances.
- the feed additives can be added to all common feeds.
- the invention also includes feed containing the feed additives of the invention and their use for animal nutrition
- feed or “animal feed” and feed additives are any substances or products which are processed, partially processed or unprocessed and intended for oral administration. Accordingly, animal feeds and feed additives may be both in solid form and in liquid form. Thus, also drinking water for animals is included.
- the feedingstuffs are feed within the meaning of Article 3 (4) of Regulation (EC) No. 178/2002.
- the feedstuffs may be either feed materials, compound feeds, premixes or additives, these being defined in LFGB ⁇ 3, numbers 1 1, 12 and 13 in the version of 26.4.2006.
- Suitable feeds may include one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or more ingredients selected from the group consisting of: corn, barley, wheat, oats, rye, triticale, sorghum , Silage (eg corn silage, grass silage), rice and bran, semolina and flours, soybeans, soya products such as soybean meal, rapeseed, rape seed extract, cottonseed and meal, sunflower seeds, sunflower seed meal, linseed, linseed meal, oil seed expeller, field beans and peas, gluten , Gelatin, tapioca, yeasts, single cell protein, fishmeal, salts, minerals, trace elements, vitamins, amino acids, oils / fats and the like.
- ingredients selected from the group consisting of: corn, barley, wheat, oats, rye, triticale, sorghum , Silage (eg corn silage, grass silage), rice and bran,
- the feeds are regularly put together so that the corresponding need for nutrients for the respective species is optimally covered.
- the feed also contains substances which, in particular, individually or in the form of preparations, are intended to be added to feed
- further ingredients may be included.
- the choice of other ingredients depends on the selected field of use and the selected dosage form of the agent thus available.
- Further constituents in the context of the present invention are, for example, the following substances: vitamins, carotenoids, trace elements, further antioxidants, enzymes, amino acids, minerals, carnitine, emulsifiers, stabilizers, preservatives, binders, anti-caking agents and / or flavorings.
- the feed and the feed additives may contain additives or carriers.
- additives or carriers is understood to mean substances in solid and liquid form which serve to improve product properties, such as dust behavior, flow properties, water absorption capacity, dissolution behavior and storage stability, for example silicates and carbonates / or mixtures thereof may be based on sugars such as lactose or maltodextrin, based on cereal or legume products such as corn cob meal, wheat bran and soybean meal, based on mineral salts including calcium, magnesium, sodium, potassium salts, as well as D - Pantothenic acid or its salts themselves (chemically or fermentatively produced D-Pantothenklasalz) be.
- Suitable liquid components are listed, for example, in US Pat. No. 7,910,604 B2, in Sp. 5, Z. 52 - Sp.10, Z. 50.
- a compilation of usable dry components can be found in US Pat. No. 7,910,604 B2, Sp. 10, Z. 15 - Sp. 1 1, No. 64.
- the terms “improvement”, “increase”, “increase”, “decrease”, “reduction”, the corresponding verbs as well as synonyms of all these terms mean a change of 1% - 100%, preferably 5% - 20% of a property compared to a control.
- prevention and / or "avoidance”
- the corresponding verbs as well as synonyms of all these terms mean that animals to which antoxidants according to the invention are administered exhibit significantly lower symptoms of oxidative stress, inflammatory processes and / or fertility problems compared to a control.
- control means identical or approximately identical animals compared with and without treatment by the feed additive according to the invention
- suitable controls is a routine component of each experimental set-up known to the person skilled in the art Animal animals around groups of animals, in a number that allows the expert to perform a statistical evaluation, In particular, a statistical evaluation can be made that indicates a significant change in characteristics, such as with the Student T-Test.
- analogous conditions means that all environmental conditions, such as food, feed, water, temperature, humidity, housing conditions, etc., are kept equal between the experiments to be compared.
- the characteristic referred to above may in one embodiment be animal health.
- animal health is used in the present invention in the same sense as EFSA (European Food Safety Authority) or the Federal Veterinary Office (BfT) and the EU as part of the Animal Health Strategy for the European Union 2007-2013.
- an improvement in animal health can also be made clear by an increase or improvement of the endogenous radical defense system and / or the reduction of inflammatory processes compared to control animals.
- animal health means the absence of diseases such as mastitis, claw inflammation and / or metritis.
- animal health means that normal values of one or more parameters are present selected from the group consisting of:
- Oxidative stress markers dROMS and / or TBARS
- TNF-alpha TNF-alpha
- interleukin 1-beta TNF-alpha
- interleukin 1-beta TNF-alpha
- interleukin 6-beta TNF-alpha
- improved animal health can also mean a faster recovery, a more easy course of disease-for example, fewer or weaker symptoms-compared to control animals.
- improved animal health in a variant of the present invention means that fewer animals within a group of experimental animals become ill and / or have disease symptoms than a group of control animals.
- a positive side effect of the use of antioxidants according to the invention is the increase in the vitamin E content in blood, milk and body tissue.
- antioxidants according to the invention are the increased expression of GPX (glutathione peroxidase) and SOD (superoxide dismutase).
- the expression per inflammatory cytokines such as TNF-alpha, interleukin 1 - beta and / or interleukin 6 is reduced.
- the support of the treatment of inflammatory processes in animals by the antioxidants according to the invention can lead to positive effects, preferably synergistic effects in the treatment, that is, the effects, such as diminution or disappearance of the symptoms, are greater or occur faster than by treatment the animals with pharmaceutical and / or medicinal agents alone, without administration of the antioxidants of the invention.
- Example 1 a) Animal nutrition For the experiments, 60 cows with the same average lactation and milk yield are used. The 60 cows are divided into 3 groups of 20 animals. To obtain a representative average, one group has the following composition: 8 cows with first lactation, 6 cows with second lactation and 6 cows with third or higher lactation.
- the cows receive their normal feed, in the form of a, TMR (Total Mixted Ration of Alfalfa, Maissillage, Dried Meat (DDGS), corn, barley and soybean meal).
- TMR Total Mixted Ration of Alfalfa, Maissillage, Dried Meat (DDGS), corn, barley and soybean meal.
- a group of 20 cows serves as a control.
- antioxidants are added according to the invention, e.g. 150 mg of a mixture of antioxidant to 1 kg / feed TM.
- This food has a recommended vitamin E content (1 000 IU / D).
- the third group contains a diet free of antioxidants but with an elevated vitamin E content (3,000 IU / D).
- the feed intake of the individual animals is determined, for example by means of the Calan gates and a Data Ranger feeding system.
- the amount of milk is determined daily.
- composition of the milk is determined monthly as part of the DHIA test (Dairy herd Information Association)
- a milk analysis is carried out to determine, for example, the fat content, protein content, lactose content, solids content, MUN (milk urea) and SCC (the number of somatic cells).
- the weight of the dairy cows and the general condition are determined on the following days: 28a. p., 21 ap, 14a. p., 7a. p., 0, 7p.p., 14 pp, 21 pp, 28p. p., 56 pp and 84p. p.
- the vitamin E content is determined in blood, liver, adipose tissue and / or milk.
- the determination is advantageously carried out on at least 10 animals from a group on the days DIM: - 21, 7 and 56, for example. A larger number of measurements is particularly advantageous.
- the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase in blood and liver is measured at the same time as described above.
- the oxidative stress on the markers dROMS and TBARS in blood is also determined at this time.
- the change in gene expression in adipose tissue and liver can be determined with a so-called Bovine Affymetrix Gene Array.
- the level of gene expression of GPX and SOD, the proinflammatory cytokines, e.g. TNF-alpha, interleukin 1 beta or interleukin 6 are determined using these DNA arrays.
- the number of somatic cells in the milk in the animals receiving anti-oxidants according to the invention was significantly lower than in the control animals, indicating a better udder health.
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Abstract
The invention relates to a new use of antioxidants for improving animal health. In particular, as a result of using antioxidants and also substances with an antioxidative effect, an increase or improvement in the endogenous radical defence system, a reduction in inflammatory processes and/or a prevention of and/or reduction in fertility problems is achieved.
Description
VERWENDUNG VON ANTIOXIDANTIEN ZUR VERBESSERUNG DER USE OF ANTIOXIDANTS TO IMPROVE THE
TIERGESUNDHEIT ANIMAL HEALTH
Die Erfindung betrifft eine neue Verwendung von Antioxidantien zur Verbesserung der Tiergesundheit. Insbesondere wird durch die Verwendung von Antioxidantien sowie Stoffen mit antioxidativer Wirkung eine Erhöhung bzw. Verbesserung des endogenen Radikal-Abwehr- Systems, eine Reduktion inflammatorischer Prozesse und/oder eine Verhinderung und/oder Verringerung von Fruchtbarkeitsproblemen erzielt. In den letzten Jahrzehnten hat sich der Bedarf an Lebensmitteln weltweit erhöht. Als Folge fand eine Intensivierung der Produktion, insbesondere auch im Bereich der Fleisch- und Milchproduktion, statt. Die erhöhte Tierzahl bringt allerdings auch Probleme mit sich. Infektionen können sich leichter ausbreiten und betreffen schneller eine Vielzahl von Verbrauchern. Besonders im Bereich der hochleistenden Tieren ist es wichtig, Infektionen zu vermeiden bzw. die Ausbreitung von Krankheiten schnell einzudämmen. Hierzu werden prophylaktische Anstrengungen unternommen, die sich vor allem auf die Hygiene in den Betrieben konzentrieren. The invention relates to a new use of antioxidants for improving animal health. In particular, an increase or improvement of the endogenous radical defense system, a reduction of inflammatory processes and / or a prevention and / or reduction of fertility problems is achieved by the use of antioxidants and antioxidant substances. In recent decades, the need for food has increased worldwide. As a result, there was an intensification of production, especially in the area of meat and milk production. The increased number of animals, however, also brings problems. Infections can spread more easily and affect a variety of consumers more quickly. Especially in the field of high-performing animals, it is important to avoid infections or to reduce the spread of diseases quickly. For this purpose, prophylactic efforts are made, which focus primarily on the hygiene in the farms.
Zu gefährlichen Erregern von Krankheiten gehören insbesondere Bakterien. Krankheiten, die durch Bakterien hervorgerufen werden und Nutztiere gefährden sind, insbesondere in der Milchwirtschaft z.B. die Mastitis, die Klauenentzündung und die Metritis. Diese stellen eine der Hauptursachen für die Verluste in der Milchindustrie dar. Dangerous pathogens of diseases include in particular bacteria. Diseases caused by bacteria and endangering livestock, in particular in the dairy industry e.g. Mastitis, phlegmitis and metritis. These are one of the main causes of losses in the dairy industry.
Die herkömmliche Behandlung erfolgt meistens durch Verabreichung von Antibiotika. Die Verabreichung von Antibiotika führte auch zu einer Steigerung der Lebendmassezunahme. Diese Wirkung ist nicht nur auf einen allgemein verbesserten Gesundheitszustand der Tiere zurückzuführen, sondern auch auf eine bessere Nutzung der Nährstoffe sowie der Futterenergie. Neben den relative hohen Ausgaben für den Wirkstoff und der Gefahr des Entstehens neuer, Antibiotika-resistenter Bakterienstämme sind noch weitere Nachteile zu vermerken, wie z.B. der Verbleib von Antibiotikaresten in Milch und Fleisch, sowie die dadurch sich ergebende Aufnahme in die menschliche Nahrungskette. Conventional treatment is usually by administration of antibiotics. The administration of antibiotics also resulted in an increase in the weight gain. This effect is not only due to a generally improved state of health of the animals, but also to a better use of nutrients and feed energy. In addition to the relatively high costs of the active ingredient and the risk of developing new, antibiotic-resistant bacterial strains, further disadvantages are to be noted, such as e.g. the retention of antibiotic residues in milk and meat, and the resulting uptake into the human food chain.
Um die Nachteile einer Behandlung mit Antibiotika zu vermeiden, wurde z.B. in der DE 00001971 15952 A1 ein Verfahren und einen Apparat zur Verwendung darin zur Verfügung
gestellt, bei welchem Ozon durch eine Zitzenöffnung einer Brust ins Innere der Brust eingespritzt wird. Ein Nachteil dieses Verfahrens ist jedoch, dass die Behandlung jedes Nutztieres einzeln erforderlich ist. Eine Aufnahme von Wirkstoffen über die Nahrung wäre bedeutend einfacher. In order to avoid the disadvantages of a treatment with antibiotics, for example, DE 00001971 15952 A1 has made available a method and an apparatus for use therein in which ozone is injected through a teat opening of a breast into the interior of the breast. A disadvantage of this method, however, is that the treatment of each farm animal is required individually. Taking in nutrients would be much easier.
Um die Erkrankung von Nutztieren und die Ausbreitung von Krankheiten zu verhindern, wurden lange Jahre vorsorglich, vor dem Auftreten von Krankheitssymptomen, Antibiotika verfüttert. To prevent the disease of livestock and the spread of disease, antibiotics were fed for many years as a precaution, before the onset of disease symptoms.
Innerhalb der Europäischen Union wurde in der Europäischen Union Antibiotika die Zulassung als Prophylaxe in Futtermitteln entzogen. Within the European Union, antibiotics have been withdrawn in the European Union as prophylaxis in feed.
Zur Prävention von Mastitis werden z.B. antiseptische Emulsionen oder Desinfektionsmittel vorgeschlagen, mit denen das Euter des Milchviehs behandelt wird. In der DE 1 1 2008 003749 T5 wird z.B. eine antiseptische Zusammensetzung, umfassend 10 bis 50 Vol.% Zitronengrasöl eingesetzt. Auch gegenüber solchen Verfahren, in denen eine Applikation der Wirkstoffe auf die Euter erforderlich ist, wäre eine Aufnahme von Wirkstoffen durch die Nahrung eine einfachere und kostengünstigere Lösung. For the prevention of mastitis, e.g. Antiseptic emulsions or disinfectants are proposed, with which the udder of the dairy cattle is treated. In DE 1 1 2008 003749 T5, e.g. an antiseptic composition comprising from 10 to 50% by volume of lemongrass oil. Also, compared to such methods in which an application of the active ingredients to the udder is required, a dietary intake of active ingredients would be a simpler and less expensive solution.
Zur Reduzierung entzündlicher Prozesse, insbesondere bei älteren Haustieren, wurde in der DE 000060217319 T2 die Verwendung eines Präbotikums vorgeschlagen, das aus einem Oligosaccharid erzeugt wurde. Eine Verminderung inflammatorischer Prozesse wurde allerdings lediglich durch die verminderte Expression der IL-6 mRNA Immunozyten des peripheren Bluts nahe gelegt. Gemäß der Lehre des US-Patents US 7,910,604 wird eine Mischung aus mindestens zwei Antioxidantien, wobei eines davon eine Chinolinverbindung ist, dem Futter zugesetzt, um eine Oxidation der im Futter enthaltenen Fette und Lipide auch nach der Verfütterung an Wiederkäuer zu verhindern. Es wird vermutet, dass sich dadurch der antioxidative Status der Wiederkäuer verbessern könnte. In order to reduce inflammatory processes, in particular in older domestic animals, DE 000060217319 T2 proposes the use of a prebiotic which was produced from an oligosaccharide. However, a reduction in inflammatory processes was suggested only by the reduced expression of IL-6 mRNA peripheral blood immunocytes. According to the teachings of US Pat. No. 7,910,604, a mixture of at least two antioxidants, one of which is a quinoline compound, is added to the feed to prevent oxidation of the fats and lipids contained in the feed, even after feeding to ruminants. It is thought that this could improve the antioxidant status of ruminants.
Futterzusätze mit antioxidativen Wirkungen sind ferner aus DE 600 30 253 T2, US 6,156,355, EP 1 392 131 B1 , WO 01/58271 A1 , WO 2004/091307 A2 und CA 26 183 80 A1 bekannt. Der human- und tiermedizinische Einsatz von antioxidativen Zusammensetzungen ist ferner in DE 696 17 945 T2, DE 60 2004 013 441 T2, WO 2004/1 12776 A2 und WO 2009/108120 A1 beschrieben.
Eine Vorhersage der Wirkung und insbesondere der Effektivität von Antioxidantien ist nicht möglich, da Wirkung und Effektivität nicht auf einzelne Oxidationsreaktionen begrenzt sind, sondern abhängig von zahlreichen Einflussgrößen und komplexen Zusammenhängen auf Zellebene und sogar Tierebene sind. Feed additives with antioxidant effects are also known from DE 600 30 253 T2, US Pat. No. 6,156,355, EP 1 392 131 B1, WO 01/58271 A1, WO 2004/091307 A2 and CA 26 183 80 A1. The human and veterinary use of antioxidant compositions is further described in DE 696 17 945 T2, DE 60 2004 013 441 T2, WO 2004/1 12776 A2 and WO 2009/108120 A1. A prediction of the effect and in particular the effectiveness of antioxidants is not possible, since the effect and effectiveness are not limited to individual oxidation reactions, but are dependent on numerous parameters and complex relationships at the cellular level and even at the animal level.
Es besteht ein Bedarf an Stoffen, insbesondere Zusatzstoffe für Futtermittel, um oxidativen Stress in Tieren zu vermeiden. Ferner sollen auch inflammatorische Prozesse, wie z.B. Mastitis, Metritis, Laminitis und/oder bakterielle Infektionen reduziert, verhindert und/oder ihre Behandlung mit pharmazeutisch, medizinischen Wirkstoffen unterstützt werden. Eine Wirkung von Antioxidantien auf inflammatorische Prozesse konnte bisher noch nicht nachgewiesen werden und wurde auch noch nicht erwähnt. There is a need for substances, especially feed additives, to avoid oxidative stress in animals. Furthermore, inflammatory processes, e.g. Mastitis, metritis, laminitis and / or bacterial infections can be reduced, prevented and / or their treatment supported with pharmaceutical, medicinal agents. An effect of antioxidants on inflammatory processes has not yet been demonstrated and has not yet been mentioned.
Es besteht ferner ein erhöhter Bedarf an Stoffen, insbesondere Zusatzstoffen für Futtermittel, die prophylaktisch eingesetzt werden dürfen und können, und zu einer erhöhten bzw. verbesserten Tiergesundheit führen. Besonders vorteilhaft sind hier Stoffe, die gegenüber Antibiotika einen Preisvorteil haben und/oder ebenfalls zu einer Steigerung der Lebendmassezunahme, der Milchleistung und/oder der Tiergesundheit führen. There is also an increased demand for substances, in particular additives for animal feed, which may and may be used prophylactically and lead to increased or improved animal health. Particularly advantageous here are substances that have a price advantage over antibiotics and / or also lead to an increase in living mass gain, milk yield and / or animal health.
Eine weitere Aufgabe der vorliegenden Erfindung ist die Bereitstellung von Stoffen, die nicht nur in der Prophylaxe eingesetzt werden und nur hier wirken, sondern die auch zur unmittelbaren Unterstützung der Behandlung von Krankheiten und/oder Problemen, insbesondere Fruchtbarkeitsprobleme, eingesetzt werden können. Another object of the present invention is to provide substances which are not only used in prophylaxis and act only here, but which can also be used to directly assist in the treatment of diseases and / or problems, in particular fertility problems.
Zusätzliche Aufgabe der vorliegenden Erfindung ist die Bereitstellung von Stoffen, welche die oben genannten Aufgaben insbesondere bei Wiederkäuern erfüllen. Es sollen oxidative Prozesse reduziert werden, die im Verdauungstrakt der Tiere stattfinden, so dass der oxidative Stress für das Tier verringert wird An additional object of the present invention is the provision of substances which fulfill the abovementioned objects, in particular in ruminants. The aim is to reduce oxidative processes that take place in the digestive tract of the animals, so that the oxidative stress for the animal is reduced
Gelöst wird die Aufgabe durch Verwendung von Antioxidantien sowie von Stoffen mit antioxidativer Wirkung zur Erhöhung und/oder Verbesserung des endogenen Radikal-Abwehr- Systems und/oder einer Reduktion inflammatorischer Prozesse. The object is achieved by using antioxidants and antioxidant substances to increase and / or improve the endogenous radical defense system and / or reduce inflammatory processes.
Eine weitere Lösung ist die Verwendung von Antioxidantien zur Reduzierung von inflammatorischen Prozessen und/oder Fruchtbarkeitsproblemen. Another solution is the use of antioxidants to reduce inflammatory processes and / or fertility problems.
Weitere Lösung ist die Verwendung von Antioxidantien zur Unterstützung der Behandlung von
inflammatorischen Prozessen und/oder Fruchtbarkeitsproblemen. Another solution is the use of antioxidants to help treat inflammatory processes and / or fertility problems.
In einer weiteren Variante der vorliegenden Erfindung werden Antioxidantien zur Verbesserung der Tiergesundheit sowie zur Erhöhung des endogenen Radikalabwehrsystems und/oder zur Reduktion inflammatorischer Prozesse so eingesetzt, dass Marker für oxidativen Stress wie z.B. dROMS (derivates of reactive oxygen metabolites) und TBARS ( In a further variant of the present invention, antioxidants are used to improve animal health and to increase the endogenous radical defense system and / or to reduce inflammatory processes in such a way that markers for oxidative stress, such as e.g. dROMS (derivatives of reactive oxygen metabolites) and TBARS (
Thiobarbituric acid reactive substances ) im Blut reduziert werden. Thiobarbituric acid reactive substances) are reduced in the blood.
Insbesondere wirkt sich der erfindungsgemäße Einsatz von Antioxidationsmitteln bei Milchkühen in der Transitphase sowie in der Phase der Hochlaktation positiv auf die Tiergesundheit, bevorzugt auf die Eutergesundheit aus, ausgedrückt durch eine geringere Zellzahl (Somatic cell count, SCC) in der Milch sowie durch eine Veränderung des Niveaus der Genexpression von GPX, SOD, Katalase und der proinflammatorischen Zytokine wie z.B. TNF-alpha, Interleukin 1 Beta oder Interleukin 6. In particular, the use according to the invention of antioxidants in dairy cows in the transit phase and in the phase of high lactation has a positive effect on animal health, preferably on udder health, expressed by a lower cell count (Somatic cell count, SCC) in the milk and by a change in the milk Levels of gene expression of GPX, SOD, catalase and proinflammatory cytokines such as TNF-alpha, interleukin 1 beta or interleukin 6.
Im Folgenden steht der Begriff „Antioxidantien" für Antioxidantien ebenso wie für Stoffe mit antioxidativer Wirkung, wobei Singular und Plural dieser Begriffe gleichwertig sind. In the following, the term "antioxidants" for antioxidants as well as for substances with antioxidant effect, where singular and plural of these terms are equivalent.
Antioxidantien im Sinne der vorliegenden Erfindung sind Stoffe, welche freie Radikale binden und so deren schädliche Wirkung verhindern. Antioxidants in the context of the present invention are substances which bind free radicals and thus prevent their harmful effects.
Antioxidantien können Stoffe sein, die freie Radikale einfangen und so Kettenreaktionen blockieren. Es können aber auch Stoffe mit reduzierenden Eigenschaften sein, d.h. Stoffe, die leicht oxidiert werden, ohne schädliche Produkte zu bilden. In diesem Fall müssen die Antioxidantien ein geringeres Redoxpotential als die zu schützenden Stoffe vorweisen. Unter Antioxidantien sind jedoch auch Stoffe zu verstehen, welche die antioxidative Wirkung anderer verstärken und zu der Gruppe der synergetischen Antioxidantien gezählt werden. Antioxidants can be substances that trap free radicals and block chain reactions. However, they may also be substances with reducing properties, i. Substances that are easily oxidized without forming harmful products. In this case, the antioxidants have a lower redox potential than the substances to be protected. However, antioxidants are also substances which enhance the antioxidant action of others and are included in the group of synergistic antioxidants.
Eine Ausführungsform der vorliegenden Erfindung betrifft die Verwendung von Antioxidantien sowie von Stoffen mit antioxidativer Wirkung zur Herstellung eines Mittels zur Vorbeugung und Unterstützung der Behandlung von inflammatorischen Prozessen bei Tieren, bevorzugt ausgewählt aus der Gruppe bestehend aus Mastitits, ,Metritis, Laminitis und Fruchtbarkeitsproblemen. Die folgenden Ausführungsformen betreffen sowohl die Verwendung von Antioxidantien zur Verbesserung der Tiergesundheit, als auch deren Verwendung zur Unterstützung der
Behandlung von inflammatonschen Prozessen und Unterstützung der Behandlung von Fruchtbarkeitsproblemen. One embodiment of the present invention relates to the use of antioxidants as well as antioxidant agents for the preparation of an agent for preventing and assisting the treatment of inflammatory processes in animals, preferably selected from the group consisting of mastitis, metritis, laminitis and fertility problems. The following embodiments relate to both the use of antioxidants to improve animal health, as well as their use in support of animal health Treatment of inflammatory processes and support of the treatment of fertility problems.
Ferner betreffen die folgenden Ausführungsformen sowohl die Verwendung von Antioxidantien zur Verbesserung der Tiergesundheit, als auch deren Verwendung zur Herstellung eines Mittels zur Verhinderung von inflammatorischen Prozessen und Verhinderung von Fruchtbarkeitsproblemen. Further, the following embodiments relate to the use of antioxidants for improving animal health, as well as their use for the preparation of an agent for the prevention of inflammatory processes and prevention of fertility problems.
In einer weiteren Ausführungsform handelt es sich bei den inflammatorischen Prozessen um die Mastitis (Euterentzündung), Laminitis (Klauenentzündung) und/oder Metritis (Gebärmutterentzündung ). In another embodiment, the inflammatory processes are mastitis, laminitis, and / or metritis.
In einer Alternative der vorliegenden Erfindung werden Antioxidantien verwendet, um Fruchtbarkeitsprobleme zu verringern. Fruchtbarkeitsprobleme im Sinne der Erfindung betreffen eines oder mehrere Merkmale ausgewählt aus folgender Gruppe: In an alternative of the present invention, antioxidants are used to reduce fertility problems. Fertility problems in the sense of the invention relate to one or more features selected from the following group:
- einen geringen Besamungsindex. - a low insemination index.
- eine verlängerte Zwischentragezeit. - an extended intermediate carrying time.
- eine verlängerte Zwischenkalbezeit. - an extended intermediate calving period.
- eine geringe Trächtigkeitsrate aus einer Erstbesamung. - a low pregnancy rate from a first insemination.
- eine geringe Befruchtungsrate. - a low fertilization rate.
- eine geringe Anzahl der Würfe pro Tier. - a small number of litters per animal.
- eine hohe Embryosterblichkeit oder high embryo mortality or
- eine geringe Schlupfrate. - a low hatching rate.
Bei den Tieren, deren Tiergesundheit erfindungsgemäß verbessert wird, handelt es sich um Tiere, ausgewählt aus der Gruppe bestehend aus landwirtschaftlichen Nutztieren, z.B. Wiederkäuern, Nichtwiederkäuern, Rindern, Kühen, Milchkühen, Ziegen, Milchziegen, Schafen, Milchschafen, Schwein, Zuchtsauen, Mastgeflügeltiere, Legegeflügel, Elterntiere, Küken, Hühner, Puten, Gänse, Enten, Pferden. The animals whose animal health is improved according to the invention are animals selected from the group consisting of farm animals, e.g. Ruminants, non-ruminants, cattle, cows, dairy cows, goats, dairy goats, sheep, dairy sheep, swine, sows, broilers, poultry, parents, chicks, chickens, turkeys, geese, ducks, horses.
Besonders bevorzugt handelt es sich um Tiere, ausgewählt aus der Gruppe bestehend aus Wiederkäuern, insbesondere Rindern, Kühe, Milchkühe, Ziegen, Milchziegen, Schafe und Milchschafe, insbesondere Milchkühe. Particularly preferred are animals selected from the group consisting of ruminants, in particular cattle, cows, dairy cows, goats, dairy goats, sheep and milk sheep, in particular dairy cows.
Ebenso ist die erfindungsgemäße Verwendung bei anderen Tieren, insbesondere bei
Haustieren möglich. Beispiele sind die Verwendung bei Reitpferden, Zuchtpferd allgemein die Anwendung bei Stoffwechselstörungen von beliebigen Tieren. Likewise, the use according to the invention in other animals, especially in Pets possible. Examples are the use in riding horses, breeding horse generally the application in metabolic disorders of any animals.
Bevorzugt werden Antioxidantien verwendet ausgewählt aus der Gruppe bestehend aus BHT (E 321 ), BHA (E320), Propylgallat, (E 310), Ethoxyquin (E 324), Zitronensäure (E 330), THBQ (319), Tocopherole, Rosmarinextrakt, sowie Carnitin. Preferably, antioxidants are used selected from the group consisting of BHT (E 321), BHA (E320), propyl gallate, (E 310), ethoxyquin (E 324), citric acid (E 330), THBQ (319), tocopherols, rosemary extract, and carnitine.
In einer weiteren Ausführung der vorliegenden Erfindung wird eine Kombination von Antioxidantien eingesetzt, enthaltend mindestens ein Antioxidans ausgewählt aus der Gruppe bestehend aus BHT (E 321 ), BHA (E320), Propylgallat (E310), Ethoxyquin (E 324), Zitronensäure (E 330), THBQ (E 319), sowie Carnitin. In a further embodiment of the present invention, a combination of antioxidants is used, comprising at least one antioxidant selected from the group consisting of BHT (E 321), BHA (E320), propyl gallate (E310), ethoxyquin (E 324), citric acid (E 330 ), THBQ (E 319), as well as carnitine.
Besonders bevorzugt wird eine Kombination dieser Antioxidantien als Antioxidantien-Mischung eingesetzt. It is particularly preferable to use a combination of these antioxidants as an antioxidant mixture.
Weitere Antioxidantien, die allein oder in Kombination untereinander oder mit den o.g. eingesetzt werden können, werden ausgewählt aus der Gruppe bestehend aus: Further antioxidants, alone or in combination with each other or with the o.g. can be used are selected from the group consisting of:
E220-E228:Schwefeldioxid und • E350-E352:Malatsalze E220-E228: sulfur dioxide and • E350-E352: malate salts
Salze der schwefligen Säure • E354: Calciumtartrat Salts of sulphurous acid • E354: calcium tartrate
E300-E302, E304:Ascorbinsäure, • E355: Adipinsäure E300-E302, E304: ascorbic acid, • E355: adipic acid
ihre Salze und Fettsäureester • E356: Natriumadipat their salts and fatty acid esters • E356: sodium adipate
E306-E309:Tocopherol und seine • E357: Kaliumadipat E306-E309: tocopherol and its • E357: potassium adipate
Ester • E363: Bernsteinsäure und/oder deren Ester • E363: succinic acid and / or its
E315, E316:lsoascorbinsäure und Salze E315, E316: isoascorbic acid and salts
Natriumsalz • E380: Triammoniumcitrat Sodium salt • E380: triammonium citrate
E310-E312:Gallate • E385: Calciumdinatriumethylen- E310-E312: Gallate • E385: calcium disodium ethylene
E319:tert-Butylhydrochinon (TBHQ) diamin-tetraacetat (CaNa2EDTA)E319: tert-butylhydroquinone (TBHQ) diamine tetraacetate (CaNa2EDTA)
E320:Butylhydroxyanisol (BHA) • E392:Rosmarinextrakt (wirksameE320: butylhydroxyanisole (BHA) • E392: rosemary extract (effective
E321 :Butylhydroxytoluol (BHT) Inhaltsstoffe insbesondere CarnosolE321: Butylated hydroxytoluene (BHT) Ingredients especially Carnosol
E330-E333: Citronensäure und Salze und Carnosolsäure) E330-E333: citric acid and salts and carnosic acid)
der Citronensäure • E586:4-Hexylresorcin citric acid • E586: 4-hexylresorcinol
E334-E337: Weinsäure und Salze der • N-acetylcystein E334-E337: tartaric acid and salts of • N-acetylcysteine
Weinsäure • Benzyl-isothiocyanat Tartaric acid • Benzyl isothiocyanate
E338-E343: Phosphorsäure und • Aminobenzoesäure, Dihydroxy- Salze der Phosphorsäure benzoesäure
Caffeinsäure • Gluconsäure E338-E343: phosphoric acid and • aminobenzoic acid, dihydroxy salts of phosphoric acid benzoic acid Caffeic acid • gluconic acid
Alpha-, beta-Carotenarotene • Hydroxyzimtsäure Alpha, beta-carotenarotene • hydroxycinnamic acid
Carvacrol • Hydroxytyrosol Carvacrol • hydroxytyrosol
Chlorogensäure • Apfelsäure und/oder deren Salze Chlorogenic acid • malic acid and / or its salts
Canthaxantin • Hydroxyhamstoff Canthaxantine • Hydroxyurea
Carnosol • Hydroxyglutarsäure Carnosol • Hydroxyglutaric acid
Eugenol • Thymol Eugenol • Thymol
Caryophyllen • Rosmarinsäure und/oder Salze davon Caryophyllene • rosmarinic acid and / or salts thereof
Extrakte aus Gewürznelken, • Maltol Extracts of cloves, • maltol
Kaffeebohnen, Eukalyptus, Rosmarin, • Sesamol Coffee beans, eucalyptus, rosemary, • Sesamol
Kleie, Salbei, Weizenkeimlingen • Hydroxybenzylphophinsäure und/oder Piment • Esculetin Bran, sage, wheat seedlings • Hydroxybenzylphophinic acid and / or allspice • Esculetin
Ellagsäure • Silymarin Ellagic acid • silymarin
Trimethylquinolin sowie substituierte • Trihydroxybutyrophenon Trimethylquinoline and substituted trihydroxybutyrophenone
Trimethylquinoline • Tyramin Trimethylquinoline • tyramine
Flavonoide, Flavon und/oder • Q10 Flavonoids, flavones and / or • Q10
Flaovonol, Flavonanon • Methylgallat Flaovonol, flavonanone • methyl gallate
Gallsäure • Monoglyceridcitrat Gallic acid • monoglyceride citrate
Coumarinsäure • Phenothiazin Coumaric acid • phenothiazine
Thiodipropionat-Fettsäure-ester • Gum gaiacum Thiodipropionate fatty acid ester • Gum gaiacum
Buthylphenol • Ferulinsäure Butylphenol • Ferulic acid
Erythorbinsäure und/oder Salze • Stearylcitrat Erythorbic acid and / or salts • Stearyl citrate
davon • Tocotrienol of which • tocotrienol
Fumarinsäure • Tryptamin Fumaric acid • tryptamine
Hesperitin • Tyrosol Hesperitin • tyrosol
Glycin • Vanilinsäure Glycine • Vanilic acid
Zeaxanthin • lonox, zum Beispiel 100, 300 Zeaxanthin • lonox, for example 100, 300
Oxalsäure und/oder Salze davon • Harnsäure Oxalic acid and / or salts thereof • uric acid
Fraxetin • Liponsäure Fraxetine • Lipoic Acid
Lecithin • Esculin Lecithin • Esculin
Lutein • DPPD (N,N'-Diphenyl-p- Lutein • DPPD (N, N'-diphenyl-p-)
Lycopen phenyldiamin) Lycopene phenyldiamine)
Hydroquinon • Epigallocatechin und/oder dessen Hydroquinone • epigallocatechin and / or its
Milchsäure und/oder Salze davon Gallat
Quercitin Naphthoflavon Lactic acid and / or salts thereof, gallate Quercitin naphthoflavone
6-Ethoxy-1 ,2-dihydro-2,2,4- 5-Methoxytryptamine 6-ethoxy-1,2-dihydro-2,2,4-5-methoxytryptamine
trimethylquinolin N o rhyd rog u aj a retsä u re trimethylquinoline N o rhyd rog u aj a retsä u re
Morin Sinapinsäure Morin sinapinic acid
Vitamin K Resveratrol (trans-) Vitamin K resveratrol (trans-)
Phosphatidylcholin Thiodipropionsäure Phosphatidylcholine thiodipropionic acid
Polyphosphat Syringinsäure Polyphosphate syringic acid
Propylgallat Phytylubichromel Propyl gallate Phytylubichromel
Palmitylcitrat Octylgallat Palmityl citrate octyl gallate
Antioxidantien-Mischungen: Pulver Antioxidant Blends: Powder
Eine bevorzugte Antioxidantien-Mischung enthält 5 bis 25 Gew.% BHT (E 321 ), 1 bis 10 Gew.% Propylgallat (E 310), 1 bis 5 % Ethoxyquin (E 324), 1 -5% TBHQ und/oder 10 bis 50% Zitronensäure (E 330). A preferred antioxidant mixture contains 5 to 25 wt% BHT (E 321), 1 to 10 wt% propyl gallate (E 310), 1 to 5% ethoxyquin (E 324), 1 to 5% TBHQ and / or 10 to 50% citric acid (E 330).
In einer bevorzugten Ausführung enthält die Antioxidantien-Mischung 10 bis 20 Gew.% BHT, 3 bis 8 % Propylgallat, 2 bis 4 % Ethoxyquin, 2 bis 4 % TBHQ und/oder 15 bis 40 % Zitronensäure. In a preferred embodiment, the antioxidant mixture contains 10 to 20 wt% BHT, 3 to 8% propyl gallate, 2 to 4% ethoxyquin, 2 to 4% TBHQ, and / or 15 to 40% citric acid.
Eine besonders bevorzugte Antioxidantien-Mischung enthält 17 % BHT, 6 % Propylgallat, 2%, Ethoxyquin, 4 % TBHQ und/oder 25 % Zitronensäure. A particularly preferred antioxidant mixture contains 17% BHT, 6% propyl gallate, 2%, ethoxyquin, 4% TBHQ and / or 25% citric acid.
In einer weiteren Ausführung enthält die Antioxidantien-Mischung 5 bis 15% Rosmarinextrakt, 5 bis 20% natürliches Tocopherol, 1 bis 10% TBHQ und/oder 1 bis 5% BHT, bevorzugt 7,5% Rosmarinextrakt, 10% natürliches Tocopherol, 5% TBHQ und/oder 3,2% BHT. In a further embodiment, the antioxidant mixture contains 5 to 15% rosemary extract, 5 to 20% natural tocopherol, 1 to 10% TBHQ and / or 1 to 5% BHT, preferably 7.5% rosemary extract, 10% natural tocopherol, 5% TBHQ and / or 3.2% BHT.
In einer weiteren Ausführungsform enthält die Antioxidantien-Mischung 10 bis 30 % Propylgallat, 1 bis 10 % BHA (E 320), 1 bis 20 % Zitronensäure. In another embodiment, the antioxidant mixture contains 10 to 30% propyl gallate, 1 to 10% BHA (E 320), 1 to 20% citric acid.
In einer bevorzugten Variante enthält die Antioxidantien-Mischung 15 bis 25 % Propylgallat, 5 bis 15 % BHA und 5 bis 15 % Zitronensäure, besonders bevorzugt sind 20 % Propylgallat, 10 % BHA sowie 10 % Zitronensäure. In a preferred variant, the antioxidant mixture contains 15 to 25% propyl gallate, 5 to 15% BHA and 5 to 15% citric acid, more preferably 20% propyl gallate, 10% BHA and 10% citric acid.
Antioxidantien Mischungen: flüssig
Eine bevorzugte flüssige Antioxidantien-Mischung enthält 1 bis 20 Gew.% Propylgallat (E 310), 10 bis 40 % Ethoxyquin (E 324), 1 bis 25 % TBHQ und/oder 1 bis 15 % Zitronensäure (E 330). In einer bevorzugten Ausführung enthält die flüssige Antioxidantien-Mischung 1 bis 15 Gew.% Propylgallat (E 310), 15 bis 30 % Ethoxyquin (E 324), 1 bis 20 % TBHQ und/oder 1 bis 10 % Zitronensäure (E 330). Antioxidants mixtures: liquid A preferred liquid antioxidant mixture contains 1 to 20% by weight of propyl gallate (E 310), 10 to 40% ethoxyquin (E 324), 1 to 25% TBHQ and / or 1 to 15% citric acid (E 330). In a preferred embodiment, the liquid antioxidant mixture contains 1 to 15% by weight of propyl gallate (E 310), 15 to 30% ethoxyquin (E 324), 1 to 20% TBHQ and / or 1 to 10% citric acid (E 330).
Eine besonders bevorzugte flüssige Antioxidantien-Mischung 1 bis 10 Gew.% Propylgallat (E 310), 20 bis 30 % Ethoxyquin (E 324), 1 bis 25 % TBHQ und/oder 1 bis 8 % Zitronensäure (E 330), insbesondere 26,5% Etoxyquin, 10% TBHQ, 7,5% Propylgallat und/oder Zitronensäure 4%. A particularly preferred liquid antioxidant mixture 1 to 10% by weight of propyl gallate (E 310), 20 to 30% ethoxyquin (E 324), 1 to 25% TBHQ and / or 1 to 8% citric acid (E 330), in particular 26, 5% Etoxyquin, 10% TBHQ, 7.5% propyl gallate and / or citric acid 4%.
In einer weiteren Ausführungsform enthält die Antioxidantien-Mischung 1 -30% TBHQ, 1 -10% Propylgallat und/oder 4% Zitronensäure. In another embodiment, the antioxidant mixture contains 1-30% TBHQ, 1-10% propyl gallate and / or 4% citric acid.
Bevorzugt werden für die Antioxidantien-Mischung mindestens 2, 3, 4, 5 oder mehrere der oben genannten Antioxidantien verwendet, bevorzugt 3 oder 4, insbesondere 4. At least 2, 3, 4, 5 or more of the abovementioned antioxidants are preferably used for the antioxidant mixture, preferably 3 or 4, in particular 4.
In einer weiteren Ausführungsform wird Ethoxyquin durch THBQ ersetzt, wobei die Antioxidantien-Mischung 1 bis 20 Gew.%, bevorzugt 2 bis 10 % THBQ enthält. Die Antioxidantien-Mischung wird in einem Anteil von 1 bis 1 .000 mg je kg Futter TS, bevorzugt 50 bis 750 mg pro kg, besonders bevorzugt 75 bis 500 mg je kg, insbesondere 100 bis 200 mg je kg Futter TS eingesetzt. In another embodiment, ethoxyquin is replaced by THBQ, wherein the antioxidant mixture contains 1 to 20% by weight, preferably 2 to 10% THBQ. The antioxidant mixture is used in a proportion of 1 to 1,000 mg per kg of feed TS, preferably 50 to 750 mg per kg, more preferably 75 to 500 mg per kg, in particular 100 to 200 mg per kg of feed TS.
Die Antioxidantien-Mischung kann neben den Antioxidantien noch folgende zusätzliche Stoffe enthalten: Silikate, Salze, Carbonate, Dicalziumphosphate, Dextrine, Stärken, Dextrosen, Fettsäuren, Pflanzenöle, Emulgatoren (E490, E484, E432, E433, E434, E435, E436) In addition to the antioxidants, the antioxidant mixture may also contain the following additional substances: silicates, salts, carbonates, dicalcium phosphates, dextrins, starches, dextrose, fatty acids, vegetable oils, emulsifiers (E490, E484, E432, E433, E434, E435, E436)
Gegenstand der vorliegenden Erfindung ist ferner eine der oben beschriebenen Antioxidantien-Mischungen. Gegenstand der vorliegenden Erfindung ist außerdem ein Verfahren zur Herstellung einer der oben beschriebenen Antioxidantien-Mischungen. The subject matter of the present invention is furthermore one of the antioxidant mixtures described above. The present invention also provides a process for the preparation of one of the antioxidant mixtures described above.
Erfindungsgemäß wird eine Zusammensetzung, enthaltend Antioxidantien, dem Futter, den Futtermitteln oder dem Trinkwasser der Tiere beigemischt. According to the invention, a composition containing antioxidants, the feed, feed or drinking water of the animals is admixed.
Demgemäß betrifft die vorliegende Erfindung ein Verfahren zu Herstellung eines Tierfutters
umfassend folgende Schritte: Accordingly, the present invention relates to a method of producing an animal feed comprising the following steps:
o Herstellung einer der oben beschriebenen Antioxidantien-Mischungen, o Preparation of one of the antioxidant mixtures described above,
o Mischen der Antioxidantien-Mischung mit einem herkömmlichen Tierfutter und/oder Mix the antioxidant mixture with a conventional animal feed and / or
Futtermittel in einem Anteil von 1 bis 1 .000 mg je kg Futter TS, bevorzugt 50 bis 750 mg pro kg, besonders bevorzugt 75 bis 500 mg je kg, insbesondere 100 bis 200 mg je kg Futter TS (Trockensubstanzgehalt). Feed in a proportion of 1 to 1,000 mg per kg of feed TS, preferably 50 to 750 mg per kg, more preferably 75 to 500 mg per kg, in particular 100 to 200 mg per kg of feed TS (dry matter content).
Die Herstellung erfolgt im einfachsten Fall durch Mischen der Komponenten. The preparation is carried out in the simplest case by mixing the components.
Die einfachste Form der Mischung ist das Zusammenbringen der Komponenten in einem Mischer. Solche Mischer sind dem Fachmann bekannt. Die Mischer können diskontinuierlich oder kontinuierlich betrieben werden. Im diskontinuierlichen Mischer werden die zu mischenden Komponenten im gewünschten Verhältnis vorgelegt und dann eine hinreichende Zeit im Bereich von Minuten bis Stunden gemischt. Die Mischzeit und die Mischbeanspruchung werden so festgelegt, dass die beiden Komponenten homogen verteilt in der Mischung vorliegen. Im Fall der kontinuierlichen Mischung werden beide Komponenten kontinuierlich zugegeben, gegebenenfalls nach einer Vormischung. Auch im kontinuierlichen Mischer ist die Verweilzeit und Mischbeanspruchung so zu wählen, dass beide Komponenten homogen verteilt in der Mischung vorliegen. Die Mischung wird üblicherweise bei Raumtemperatur durchgeführt, kann aber auch bei höheren oder niedrigeren Temperaturen durchgeführt werden. In einer bevorzugten Ausführungsform werden die Mischungen bei Raumtemperaturen durchgeführt. Die Mischung kann bei Normaldruck, im Vakuum oder bei Überdruck durchgeführt werden. Für die hier beschriebenen Mischaufgaben ist die Mischung bei Normaldruck zu bevorzugen. Alternativ ist die Mischung in einer Mühle oder über eine Bewegung des gesamten Behälters möglich. Beispiele hierfür sind Taumelmischer, Trommelmischer oder ähnliches. Eine weitere Möglichkeit besteht in der Verwendung von pneumatischen Mischern. Die Mischung von Feststoffen ist beispielsweise in Ullmann's Encyclopedia of Industrial Chemistry, Sixth Edition, 2000, Mixing of Solids beschrieben. The simplest form of mixing is bringing the components together in a mixer. Such mixers are known to the person skilled in the art. The mixers can be operated discontinuously or continuously. In the batch mixer, the components to be mixed are introduced in the desired ratio and then mixed for a sufficient time in the range of minutes to hours. The mixing time and the mixing stress are determined so that the two components are homogeneously distributed in the mixture. In the case of continuous mixing, both components are added continuously, optionally after a premix. Even in a continuous mixer, the residence time and mixing stress should be selected so that both components are homogeneously distributed in the mixture. The mixture is usually carried out at room temperature, but can also be carried out at higher or lower temperatures. In a preferred embodiment, the mixtures are carried out at room temperatures. The mixture can be carried out at atmospheric pressure, in a vacuum or at elevated pressure. For the mixing tasks described here, mixing at normal pressure is to be preferred. Alternatively, the mixture is possible in a mill or over a movement of the entire container. Examples of this are tumble mixers, drum mixers or the like. Another possibility is the use of pneumatic mixers. The mixture of solids is described, for example, in Ullmann's Encyclopedia of Industrial Chemistry, Sixth Edition, 2000, Mixing of Solids.
Mischung flüssiger Antioxidantien Mixture of liquid antioxidants
In einer Variante der vorliegenden Erfindung werden die Mischungen ggf. bei Raumtemperatur durch das Zusammenbringen der Komponenten in einem Mischer und gegebenenfalls Erwärmen auf bis zu 60°C hergestellt. Gegebenenfalls wird eine Vormischung aus Teilen der Mischung hergestellt.
Gegenstand der vorliegenden Erfindung sind somit Futtermittelzusatzstoffe für Tiere enthaltend eine erfindungsgemäße Antioxidantien-Mischung und/oder hergestellt nach dem erfindungsgemäßen Verfahren sowie die Verwendung der Antioxidantien bzw. Antioxidantien- Mischung als Futtermittelzusatzstoff oder in Futtermittelzusatzstoffen bzw. entsprechenden Stoffgemischen. Die Futtermittelzusatzstoffe können allen üblichen Futtermitteln zugesetzt werden. In one variant of the present invention, the mixtures are optionally prepared at room temperature by combining the components in a mixer and optionally heating to 60 ° C. Optionally, a premix of parts of the mixture is prepared. The present invention thus relates to feed additives for animals comprising an antioxidant mixture according to the invention and / or prepared by the process according to the invention and the use of the antioxidants or antioxidant mixture as feed additive or in feed additives or corresponding mixtures of substances. The feed additives can be added to all common feeds.
Die Erfindung umfasst auch Futtermittel enthaltend die erfindungsgemäßen Futtermittelzusatzstoffe und deren Verwendung zur Tierernährung The invention also includes feed containing the feed additives of the invention and their use for animal nutrition
Im Zusammenhang mit der vorliegenden Erfindung sind unter "Futtermitteln" oder "Tierfutter" sowie Futtermittelzusatzstoffen jedwede Stoffe oder Erzeugnisse zu verstehen, die verarbeitet, teilweise verarbeitet oder unverarbeitet und die zur oralen Verabreichung bestimmt sind. Demgemäß können Tierfutter und Futtermittelzusatzstoffe sowohl in fester Form als auch in flüssiger Form vorliegen. Somit ist auch Tränkwasser für Tiere eingeschlossen. In the context of the present invention, "feed" or "animal feed" and feed additives are any substances or products which are processed, partially processed or unprocessed and intended for oral administration. Accordingly, animal feeds and feed additives may be both in solid form and in liquid form. Thus, also drinking water for animals is included.
Die Futtermittel sind Futtermittel im Sinne des Artikels 3 Nr. 4 der Verordnung (EG)Nr. 178/2002. Bei den Futtermitteln kann es sich sowohl um Einzelfuttermittel, Mischfuttermittel, Premixe, Zusatzstoffe handeln wobei diese im LFGB § 3, Ziffern 1 1 , 12 und 13 in der Fassung vom 26.4.2006 definiert sind. The feedingstuffs are feed within the meaning of Article 3 (4) of Regulation (EC) No. 178/2002. The feedstuffs may be either feed materials, compound feeds, premixes or additives, these being defined in LFGB § 3, numbers 1 1, 12 and 13 in the version of 26.4.2006.
Geeignete Futtermittel können ein, zwei, drei, vier, fünf, sechs, sieben, acht, neun, zehn, elf, zwölf oder mehr Bestandteile enthalten ausgewählt aus der Gruppe bestehend aus: Mais, Gerste, Weizen, Hafer, Roggen, Triticale, Sorghum, Silagen (z.B. Maissilage, Grassilage), Reis und Kleien, Grieskleien sowie Mehle dieser Getreidearten, Sojabohnen, Sojaprodukte wie Sojaextraktionsschrot, Raps, Rapsextraktionsschrot, Baumwollsaat und Extraktionsschrot, Sonnenblumenkerne, Sonnenblumenextraktionsschrot, Leinsaat, Leinextraktionsschrot, Expeller von Ölsaaten, Ackerbohnen und Erbsen, Gluten, Gelatine, Tapioka, Hefen, Single Cell Protein, Fischmehl, Salze, Mineralstoffe, Spurenelemente, Vitamine, Aminosäuren, Öle/Fette und dergleichen. Suitable feeds may include one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or more ingredients selected from the group consisting of: corn, barley, wheat, oats, rye, triticale, sorghum , Silage (eg corn silage, grass silage), rice and bran, semolina and flours, soybeans, soya products such as soybean meal, rapeseed, rape seed extract, cottonseed and meal, sunflower seeds, sunflower seed meal, linseed, linseed meal, oil seed expeller, field beans and peas, gluten , Gelatin, tapioca, yeasts, single cell protein, fishmeal, salts, minerals, trace elements, vitamins, amino acids, oils / fats and the like.
Die Futtermittel werden regelmäßig so zusammengesetzt, dass der entsprechende Bedarf an Nährstoffen für die jeweilige Tierart optimal gedeckt wird.
In einer weiteren Ausführungsform der vorliegenden Erfindung enthält das Futtermittel außerdem solche Stoffe, die insbesondere einzeln oder in Form von Zubereitungen dazu bestimmt sind, Futtermitteln zugesetzt zu werden, um The feeds are regularly put together so that the corresponding need for nutrients for the respective species is optimally covered. In a further embodiment of the present invention, the feed also contains substances which, in particular, individually or in the form of preparations, are intended to be added to feed
• die Beschaffenheit der Futtermittel oder der tierischen Erzeugnisse zu beeinflussen, · den Bedarf der Tiere an bestimmten Nähr- oder Wirkstoffen zu decken oder die tierische Erzeugung zu verbessern, insbesondere durch Einwirkung auf die Magen- und Darmflora oder die Verdaulichkeit der Futtermittel oder durch Verringerung von Belästigungen durch Ausscheidungen der Tiere, oder • to influence the nature of feed or animal products, • to meet the needs of animals for certain nutrients or active substances or to improve animal production, in particular by affecting the stomach and intestinal flora or the digestibility of the feedingstuffs or reducing them Harassment by excreta of the animals, or
• besondere Ernährungszwecke zu erreichen oder bestimmte zeitweilige ernährungsphysiologische Bedürfnisse der Tiere zu decken. • to achieve special nutritional purposes or to meet certain temporary nutritional needs of the animals.
In einer weiteren Ausführungsform können weitere Bestandteile enthalten sein. Die Wahl der weiteren Bestandteile richtet sich dabei nach dem gewählten Einsatzgebiet und gewählten Darreichungsform des so erhältlichen Mittels. Als weitere Bestandteile im Sinne der vorliegenden Erfindung werden beispielsweise folgende Stoffe genannt: Vitamine, Carotinoide, Spurenelemente, weitere Antioxidantien, Enzyme, Aminosäuren, Mineralstoffe, Carnitin, Emulgatoren, Stabilisatoren, Konservierungsmittel, Bindemittel, Antibackmittel und/oder Geschmacksstoffe. In a further embodiment, further ingredients may be included. The choice of other ingredients depends on the selected field of use and the selected dosage form of the agent thus available. Further constituents in the context of the present invention are, for example, the following substances: vitamins, carotenoids, trace elements, further antioxidants, enzymes, amino acids, minerals, carnitine, emulsifiers, stabilizers, preservatives, binders, anti-caking agents and / or flavorings.
In einer weiteren Ausführungsform können das Futtermittel und die Futtermittelzusatzstoffe Zuschlagstoffe bzw. Trägerstoffe enthalten. Unter "Zuschlagstoffen" bzw. „Trägerstoffen" werden Stoffe in fester und flüssiger Form verstanden, die der Verbesserung der Produkteigenschaften, wie Staubverhalten, Fließeigenschaften, Wasseraufnahmefähigkeit, Lösungsverhalten und Lagerstabilität dienen. Ebenso kommen z.B. Silikate sowie Carbonate in Betracht. Zuschlagstoffe bzw. Trägerstoffe und/oder Mischungen davon können auf der Basis von Zuckern z.B. Lactose oder Maltodextrin, auf der Basis von Getreide- oder Hülsenfruchtprodukten z.B. Maisspindelmehl, Weizenkleie und Sojaschrot, auf der Basis von Mineralsalzen u.a. Calcium-, Magnesium-, Natrium-, Kaliumsalze, sowie auch D- Pantothensäure oder deren Salze selbst (chemisch oder fermentativ hergestelltes D- Pantothensäuresalz) sein. In a further embodiment, the feed and the feed additives may contain additives or carriers. The term "additives" or "carriers" is understood to mean substances in solid and liquid form which serve to improve product properties, such as dust behavior, flow properties, water absorption capacity, dissolution behavior and storage stability, for example silicates and carbonates / or mixtures thereof may be based on sugars such as lactose or maltodextrin, based on cereal or legume products such as corn cob meal, wheat bran and soybean meal, based on mineral salts including calcium, magnesium, sodium, potassium salts, as well as D - Pantothenic acid or its salts themselves (chemically or fermentatively produced D-Pantothensäuresalz) be.
Geeignete flüssige Komponenten sind z.B. in der US 7,910,604 B2, in Sp. 5, Z. 52 - Sp.10, Z. 50 aufgezählt. Eine Zusammenstellung einsetzbarer trockener Komponenten ist in der US 7.910,604 B2, in Sp. 10, Z. 15 - Sp. 1 1 , Z. 64 zu finden. Die Begriffe „Verbesserung", „Erhöhung", „Steigerung", „Erniedrigung", „Verringerung", die
entsprechenden Verben sowie Synonyme all dieser Begriffe bedeuten eine Änderung um 1 % - 100% bevorzugt 5% - 20% einer Eigenschaft im Vergleich zu einer Kontrolle. Suitable liquid components are listed, for example, in US Pat. No. 7,910,604 B2, in Sp. 5, Z. 52 - Sp.10, Z. 50. A compilation of usable dry components can be found in US Pat. No. 7,910,604 B2, Sp. 10, Z. 15 - Sp. 1 1, No. 64. The terms "improvement", "increase", "increase", "decrease", "reduction", the corresponding verbs as well as synonyms of all these terms mean a change of 1% - 100%, preferably 5% - 20% of a property compared to a control.
Die Begriffe „Verhinderung" und/oder „Vermeidung", die entsprechenden Verben sowie Synonyme all dieser Begriffe bedeuten, dass Tiere denen erfindungsgemäß Antoxidantien zugeführt werden im Vergleich zu einer Kontrolle signifikant geringere Symptome von oxidativem Stress, inflammatorische Prozessen und/oder Fruchtbarkeitsproblemen zeigen. The terms "prevention" and / or "avoidance", the corresponding verbs as well as synonyms of all these terms mean that animals to which antoxidants according to the invention are administered exhibit significantly lower symptoms of oxidative stress, inflammatory processes and / or fertility problems compared to a control.
Der Begriff „Kontrolle" bedeutet identische bzw. annähernd identische Tiere mit und ohne Behandlung durch die erfindungsgemäßen Futtermittelzusatzstoff verglichen werden. Die Wahl von geeigneten Kontrollen ist ein dem Fachmann bekannter Routinebestandteil eines jeden Versuchsaufbaus. Vorteilhaft handelt es sich sowohl bei den Kontrolltieren als auch bei den Versuchstieren um Gruppen von Tieren, in einer Anzahl, die dem Fachmann eine statistische Auswertung erlaubt. Insbesondere kann eine statistische Auswertung erfolgen, die eine signifikante Änderung von Eigenschaften anzeigt, wie z.B. mit dem Student T-Test. The term "control" means identical or approximately identical animals compared with and without treatment by the feed additive according to the invention The choice of suitable controls is a routine component of each experimental set-up known to the person skilled in the art Animal animals around groups of animals, in a number that allows the expert to perform a statistical evaluation, In particular, a statistical evaluation can be made that indicates a significant change in characteristics, such as with the Student T-Test.
Vergleiche werden vorzugsweise jeweils unter analogen Bedingungen durchgeführt. Der Ausdruck "analoge Bedingungen" bedeutet, dass alle Umweltbedingungen wie zum Beispiel Nahrung, Futter, Wasser, Temperatur, Feuchtigkeit, Stallgegebenheiten etc. zwischen den zu vergleichenden Experimenten gleichgehalten werden. Comparisons are preferably carried out under analogous conditions. The term "analogous conditions" means that all environmental conditions, such as food, feed, water, temperature, humidity, housing conditions, etc., are kept equal between the experiments to be compared.
Die oben bezeichnete Eigenschaft kann in einer Ausführungsform die Tiergesundheit sein. Der Begriff „Tiergesundheit" wird in der vorliegenden Erfindung in der gleichen Bedeutung verwendet wie von der EFSA (Europäische Behörde für Lebensmittelsicherheit) oder dem BfT (Bundesverband für Tiergesundheit) sowie von der EU im Rahmen der Tiergesundheitsstrategie für die Europäische Union 2007 bis 2013. The characteristic referred to above may in one embodiment be animal health. The term "animal health" is used in the present invention in the same sense as EFSA (European Food Safety Authority) or the Federal Veterinary Office (BfT) and the EU as part of the Animal Health Strategy for the European Union 2007-2013.
Im Wesentlichen handelt es sich dabei nicht nur um die Abwesenheit von Krankheiten im Tier, sondern allgemein um das Wohlergehen der Tiere. Erfindungsgemäß kann eine Verbesserung der Tiergesundheit auch durch eine Erhöhung bzw. Verbesserung des endogen Radikalabwehrsystems und/oder der Reduktion inflammatorischer Prozesse gegenüber Kontrolltieren deutlich werden. Essentially, this is not just about the absence of disease in the animal, but more generally about the welfare of the animals. According to the invention, an improvement in animal health can also be made clear by an increase or improvement of the endogenous radical defense system and / or the reduction of inflammatory processes compared to control animals.
In einer Ausführung der Erfindung bedeutet Tiergesundheit die Abwesenheit von Krankheiten wie Mastitis, Klauenentzündung und/oder Metritis.
In einer bevorzugten Ausführungsform der vorliegenden Erfindung bedeutet Tiergesundheit, dass Normalwerte eines oder mehreren Parameter vorliegen, ausgewählt aus der Gruppe bestehend aus: In one embodiment of the invention, animal health means the absence of diseases such as mastitis, claw inflammation and / or metritis. In a preferred embodiment of the present invention, animal health means that normal values of one or more parameters are present selected from the group consisting of:
Marker für oxidativen Stress: dROMS und/oder TBARS, Oxidative stress markers: dROMS and / or TBARS,
- Vitamin E-Gehalt in Blut, Milch und/oder Körpergewebe, Vitamin E content in blood, milk and / or body tissue,
Expressionsniveau der GPX, Katalase und/oder SOD in Leber und Fettgewebe, und/oder Expression level of GPX, catalase and / or SOD in liver and adipose tissue, and / or
Expressionsniveau pro inflammatorischer Zytokine: TNF-Alpha, Interleukin 1 -Beta und/oder Interleukin 6. Expression level per inflammatory cytokine: TNF-alpha, interleukin 1-beta and / or interleukin 6.
Eine verbesserte Tiergesundheit kann im Sinne der vorliegenden Erfindung auch eine schnellere Genesung, ein leichterer Krankheitsverlauf - zum Beispiel weniger oder abgeschwächte Symptome - im Vergleich zu Kontrolltieren bedeuten. In Bezug auf hochleistende Tiere bedeutet verbesserte Tiergesundheit in einer Variante der vorliegenden Erfindung, dass weniger Tiere innerhalb einer Gruppe von Versuchstieren erkranken und/oder Krankheitssymptome aufweisen als eine Gruppe von Kontrolltieren. For the purposes of the present invention, improved animal health can also mean a faster recovery, a more easy course of disease-for example, fewer or weaker symptoms-compared to control animals. In terms of high yielding animals, improved animal health in a variant of the present invention means that fewer animals within a group of experimental animals become ill and / or have disease symptoms than a group of control animals.
Ein positiver Nebeneffekt der erfindungsgemäßen Verwendung von Antioxidantien ist die Erhöhung des Vitamin E-Gehalts in Blut, Milch und Körpergewebe. A positive side effect of the use of antioxidants according to the invention is the increase in the vitamin E content in blood, milk and body tissue.
Ein weiterer Effekt der erfindungsgemäßen Verwendung von Antioxidantien ist die erhöhte Expression der GPX (Glutathion-Peroxidase) und der SOD (Superoxid-Dismutase). Another effect of the use of antioxidants according to the invention is the increased expression of GPX (glutathione peroxidase) and SOD (superoxide dismutase).
Außerdem wird die Expression pro inflammatorischer Zytokine wie TNF-Alpha, Interleukin 1 - Beta und/oder Interleukin 6 verringert. In addition, the expression per inflammatory cytokines such as TNF-alpha, interleukin 1 - beta and / or interleukin 6 is reduced.
Die Unterstützung der Behandlung von inflammatorischen Prozessen bei Tieren durch die erfindungsgemäßen Antioxidantien kann zu positiven Effekten, bevorzugt synergetischen Effekten bei der Behandlung führen, das heißt, die Effekte, wie zum Beispiel Nachlassen oder Verschwinden der Symptome, sind größer oder treten schneller ein als durch Behandlung der Tiere mit pharmazeutischen und/oder medizinischen Wirkstoffen allein, ohne Verabreichung der erfindungsgemäßen Antioxidantien. The support of the treatment of inflammatory processes in animals by the antioxidants according to the invention can lead to positive effects, preferably synergistic effects in the treatment, that is, the effects, such as diminution or disappearance of the symptoms, are greater or occur faster than by treatment the animals with pharmaceutical and / or medicinal agents alone, without administration of the antioxidants of the invention.
Beispiel 1 : a)Tierernährung
Für die Versuche werden 60 Kühe mit gleicher durchschnittlicher Laktation und gleicher Milchleistung verwendet. Die 60 Kühe werden in 3 Gruppen ä 20 Tiere aufgeteilt. Um einen repräsentativen Durchschnitt zu erfassen, hat eine Gruppe die folgende Zusammensetzung: 8 Kühe mit erster Laktation, 6 Kühe mit zweiter Laktation und 6 Kühe mit dritter oder höherer Laktation. Example 1: a) Animal nutrition For the experiments, 60 cows with the same average lactation and milk yield are used. The 60 cows are divided into 3 groups of 20 animals. To obtain a representative average, one group has the following composition: 8 cows with first lactation, 6 cows with second lactation and 6 cows with third or higher lactation.
Die Kühe erhalten ihr normales Futter, in Form einer, TMR (Total Mixted Ration aus Alfalfa, Maissillage, Trockenschlempe (DDGS), , Mais, Gerste und Sojabohnenextraktionsschrot. The cows receive their normal feed, in the form of a, TMR (Total Mixted Ration of Alfalfa, Maissillage, Dried Meat (DDGS), corn, barley and soybean meal).
Eine Gruppe von 20 Kühen dient als Kontrolle. In das Futter einer zweiten Gruppe werden erfindungsgemäß Antioxidationsmittel hinzugefügt, z.B. 150 mg einer Mischung von Antioxidationsmittel auf 1 kg/Futter-TM. Dieses Futter hat einen den Empfehlungen entsprechenden Vitamin E-Gehalt (1 .000 IU/D). Die dritte Gruppe enthält ein Futter ohne Antioxidationsmittel, aber mit erhöhtem Vitamin E-Gehalt (3.000 IU/D). A group of 20 cows serves as a control. Into the feed of a second group antioxidants are added according to the invention, e.g. 150 mg of a mixture of antioxidant to 1 kg / feed TM. This food has a recommended vitamin E content (1 000 IU / D). The third group contains a diet free of antioxidants but with an elevated vitamin E content (3,000 IU / D).
Die Milchkühe werden an individuelle Fütterungsanlagen (sog. Calan-Gates) gewöhnt. Die Eingewöhnung beginnt am Tag 21 vor der Geburt (pre partum). Die Verabreichung des jeweiligen Futters beginnt am Tag 14 vor der Geburt und wird fortgeführt bis zum 84. Laktationstag. b) Messungen The dairy cows are accustomed to individual feeding systems (so-called calan gates). Familiarization begins on day 21 before birth (pre partum). Administration of each feed begins on day 14 before birth and continues until the 84th day of lactation. b) measurements
In dieser Zeit wird die Futteraufnahme der einzelnen Tiere bestimmt, beispielsweise mittels der Calan-Gates und eines Data-Ranger-Fütterungssystems. During this time, the feed intake of the individual animals is determined, for example by means of the Calan gates and a Data Ranger feeding system.
Die Milchmenge wird täglich bestimmt. The amount of milk is determined daily.
Die Zusammensetzung der Milch wird monatlich im Rahmen des DHIA-Tests bestimmt (Dairy herd Information association) The composition of the milk is determined monthly as part of the DHIA test (Dairy herd Information Association)
Alle 2 Wochen wird eine Milchanalyse durchgeführt, um beispielsweise den Fettgehalt, Proteingehalt, Laktosegehalt, Feststoffgehalt, MUN (Milchharnstoff) und SCC (die Anzahl der somatischen Zellen) zu bestimmen. Every 2 weeks, a milk analysis is carried out to determine, for example, the fat content, protein content, lactose content, solids content, MUN (milk urea) and SCC (the number of somatic cells).
Ferner wird das Gewicht der Milchkühe sowie die allgemeine Verfassung an folgenden Tagen bestimmt: 28a. p., 21 a. p., 14a. p., 7a. p., 0 ,7p.p., 14 p.p., 21 p.p., 28p. p., 56 p.p. und 84p. p .
Der Vitamin E-Gehalt wird in Blut, Leber, Fettgewebe und/oder Milch bestimmt. Vorteilhaft erfolgt die Bestimmung an mindestens 10 Tieren aus einer Gruppe an den Tagen DIM: - 21 , 7 und 56 beispielsweise. Eine größere Anzahl von Messungen ist besonders vorteilhaft. Die Aktivität der Glutathionperoxidase (GPX), Superoxiddismutase (SOD) und Katalase in Blut und Leber wird zur selben Zeit wie oben beschrieben gemessen. Furthermore, the weight of the dairy cows and the general condition are determined on the following days: 28a. p., 21 ap, 14a. p., 7a. p., 0, 7p.p., 14 pp, 21 pp, 28p. p., 56 pp and 84p. p. The vitamin E content is determined in blood, liver, adipose tissue and / or milk. The determination is advantageously carried out on at least 10 animals from a group on the days DIM: - 21, 7 and 56, for example. A larger number of measurements is particularly advantageous. The activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase in blood and liver is measured at the same time as described above.
Ferner wird zu diesem Zeitpunkt auch der oxidative Stress über die Marker dROMS und TBARS in Blut bestimmt. Furthermore, the oxidative stress on the markers dROMS and TBARS in blood is also determined at this time.
Zusätzlich kann die Veränderung der Genexpression in Fettgewebe und Leber mit einem sog. Bovine Affymetrix Gene Array bestimmt werden. Insbesondere wird das Niveau der Genexpression von GPX und SOD, den proinflammatorischen Zytokinen wie z.B. TNF-alpha, Interleukin 1 Beta oder Interleukin 6 mit diesen DNA-Arrays bestimmt. In addition, the change in gene expression in adipose tissue and liver can be determined with a so-called Bovine Affymetrix Gene Array. In particular, the level of gene expression of GPX and SOD, the proinflammatory cytokines, e.g. TNF-alpha, interleukin 1 beta or interleukin 6 are determined using these DNA arrays.
Beispiel 2: Tierernährung Example 2: Animal nutrition
134 Milchkühe wurden in diesem Versuch eingesetzt. Diese wurden in eine Versuchsgruppe, die 150mg Antioxidantien/kg Futter Trockensubstanz zusätzlich zur normalen Ration erhielten und eine Kontrollgruppe ohne zusätzliche Antioxidantienergänzung aufgeteilt ( 67 Tiere pro Gruppe). Bei der Gruppenzuteilung wurden die Laktationszahl und die Milchleistung berücksichtigt. Die Fütterung bestand aus einer Teil-TMR (Grassilage, Maissilage, Biertreber) und zusätzlicher leistungsabhängiger Kraftfuttergabe (Gerste, Weizen, Mais, Mineralfutter) Milchmenge, Inhaltsstoffe und Zellzahlgehalte wurden über einen Zeitraum von 5 Monaten alle zwei Wochen ermittelt. 134 dairy cows were used in this trial. These were divided into a study group receiving 150 mg antioxidants / kg diet dry matter in addition to the normal diet and a control group without additional antioxidant supplementation (67 animals per group). The group allocation included lactation and milk yield. The feeding consisted of a partial TMR (grass silage, corn silage, spent grains) and additional performance-based concentrate feed (barley, wheat, corn, mineral feed). Milk quantity, ingredients and cell count were determined every two weeks over a period of 5 months.
Die Anzahl der somatischen Zellen in der Milch bei den Tieren, die erfindungsgemäß Antioxidationsmittel erhielten (150mg/ kg Futter Trockensubstanz) war signifikant geringer als bei den Kontrolltieren, was auf eine bessere Eutergesundheit hindeutet.
The number of somatic cells in the milk in the animals receiving anti-oxidants according to the invention (150 mg / kg diet dry matter) was significantly lower than in the control animals, indicating a better udder health.
Claims
1 . Verwendung von Antioxidantien sowie Stoffen mit antioxidativer Wirkung zur Erhöhung / Verbesserung des endogenen Radikal-Abwehr-Systems (eRDS) und/oder zur Reduktion inflammatorischer Prozesse. 1 . Use of antioxidants and antioxidant substances to increase / improve the endogenous radical defense system (eRDS) and / or to reduce inflammatory processes.
2. Verwendung gemäß Anspruch 1 dadurch gekennzeichnet, dass es sich bei den 2. Use according to claim 1, characterized in that it is in the
inflammatorischen Prozessen um Euterentzündungen (Mastitis), Klauenentzündungen und/oder Metritis handelt Inflammatory processes are mastitis, claw inflammation and / or metritis
3. Verwendung gemäß Anspruch 1 dadurch gekennzeichnet, dass es sich um 3. Use according to claim 1, characterized in that it is
Verhinderung und/oder Verringerung von Fruchtbarkeitsproblemen handelt. Prevention and / or reduction of fertility problems.
4. Verwendung gemäß Anspruch 1 dadurch gekennzeichnet, dass es sich um Tiere 4. Use according to claim 1, characterized in that it is animals
handelt, ausgewählt aus der Gruppe, bestehend aus landwirtschaftlichen Nutztieren, Wiederkäuern und Nichtwiederkäuern, Rindern, Kühen, Milchkühen, Ziegen, selected from the group consisting of livestock, ruminants and non-ruminants, cattle, cows, dairy cows, goats,
Milchziegen, Schafe, Milchschafe, Schweinen, Zuchtsauen, Geflügel, Mastgeflügel- und Legegeflügelelterntieren, Küken, Hühner, Puten, Gänsen, Enten, Pferden, besonders bestehend aus Wiederkäuern, insbesondere Rindern, Kühe, Milchkühe, Ziegen, Milchziegen, Schafe und Milchschafe, bevorzugt Milchkühe. Dairy goats, sheep, dairy sheep, pigs, sows, poultry, poultry and laying poultry, chicks, chickens, turkeys, geese, ducks, horses, especially ruminants, in particular cattle, cows, dairy cows, goats, milking goats, sheep and milk sheep Dairy cows.
5. Verwendung gemäß Anspruch 1 dadurch gekennzeichnet, dass es sich um eine 5. Use according to claim 1, characterized in that it is a
Kombination von Antioxidantien handelt, ausgewählt aus der aus der Gruppe, bestehend aus BHT (E321 ), BHA, Propylgallat (E310), Ethoxyquin (E324), Combination of antioxidants selected from the group consisting of BHT (E321), BHA, propyl gallate (E310), ethoxyquin (E324),
Zitronensäure (E330), THBQ (E319) sowie Carnitin. Citric acid (E330), THBQ (E319) and carnitine.
6. Verwendung gemäß Anspruch 1 dadurch gekennzeichnet, dass die Antioxidantien als Antioxidantien-Mischung in einem Anteil von 1 bis 1 .000 mg je kg Futter TS, bevorzugt 50 bis 750 mg pro kg, besonders bevorzugt 75 bis 500 mg je kg, insbesondere 100 bis 200 mg je kg Futter TS (Trockensubstanzgehalt) eingesetzt wird. 6. Use according to claim 1, characterized in that the antioxidants as an antioxidant mixture in a proportion of 1 to 1, 000 mg per kg of feed TS, preferably 50 to 750 mg per kg, more preferably 75 to 500 mg per kg, in particular 100 up to 200 mg per kg of feed TS (dry matter content) is used.
7. Verwendung gemäß Anspruch 1 dadurch gekennzeichnet, dass als Antioxidantien eine Antioxidantien-Mischung mit 5 bis 25 Gew.% BHT (E 321 ), 1 bis 10 Gew.% Propylgallat (E 310), 1 bis 5 % Ethoxyquin (E 324), 1 -5% TBHQ und/oder 10 bis 50% Zitronensäure (E 330) und/oder eine Antioxidantien-Mischung mit 1 bis 20 Gew.% Propylgallat (E 310), 10 bis 40 % Ethoxyquin (E 324), 1 bis 25 % TBHQ und/oder 1 bis 15 % 7. Use according to claim 1, characterized in that as antioxidants an antioxidant mixture with 5 to 25 wt.% BHT (E 321), 1 to 10 wt.% Propyl gallate (E 310), 1 to 5% ethoxyquin (E 324) , 1 -5% TBHQ and / or 10 to 50% citric acid (E 330) and / or an antioxidant mixture containing 1 to 20% by weight of propyl gallate (E 310), 10 to 40% ethoxyquin (E 324), 1 to 25% TBHQ and / or 1 to 15%
1 Zitronensäure (E 330) und/oder eine Antioxidantien-Mischung mit 10 bis 30 % 1 Citric acid (E 330) and / or an antioxidant mixture with 10 to 30%
Propylgallat, 1 bis 10 % BHA (E 320), 1 bis 20 % Zitronensäure und/oder eine Antioxidantien-Mischung mit 5 bis 15% Rosmarinextrakt, 5 bis 20% natürliches Tocopherol, 1 bis 10% TBHQ und/oder 1 bis 5% BHT verwendet wird. Propyl gallate, 1 to 10% BHA (E 320), 1 to 20% citric acid and / or an antioxidant mixture with 5 to 15% rosemary extract, 5 to 20% natural tocopherol, 1 to 10% TBHQ and / or 1 to 5% BHT is used.
8. Verwendung gemäß Anspruch 1 dadurch gekennzeichnet, dass die Konzentration der Marker für oxidativen Stress im Blut reduziert werden. 8. Use according to claim 1, characterized in that the concentration of the markers for oxidative stress in the blood are reduced.
9. Verwendung von Antioxidantien zur Prophylaxe und/oder Unterstützung der 9. Use of antioxidants for the prophylaxis and / or support of
Behandlung von inflammatorischen Prozessen und/oder Fruchtbarkeitsproblemen. Treatment of inflammatory processes and / or fertility problems.
10. Verfahren zur Verbesserung der Tiergesundheit, dadurch gekennzeichnet, dass 10. A method for improving animal health, characterized in that
Antioxidantien und/oder Stoffe mit antioxidativer Wirkung als Futterergänzungsmittel verfüttert werden. Antioxidants and / or substances with antioxidant effects are fed as feed supplements.
1 1 . Verfahren zur Unterstützung der Behandlung von inflammatorischen Prozessen 1 1. Method for supporting the treatment of inflammatory processes
und/oder Fruchtbarkeitsprobleme, dadurch gekennzeichnet, dass Antioxidantien und/oder Stoffe mit antioxidativer Wirkung als Futtergänzungsmittel verfüttert werden. and / or fertility problems, characterized in that antioxidants and / or substances with antioxidant activity are fed as feed supplements.
12. Verfahren nach Anspruch 1 1 dadurch gekennzeichnet, dass die inflammatorischen12. The method according to claim 1 1, characterized in that the inflammatory
Prozesse ausgewählt werden aus der Gruppe bestehend aus Mastitis, Processes are selected from the group consisting of mastitis,
Klauenentzündung, Metritis und Fruchtbarkeitsproblemen. Claw inflammation, metritis and fertility problems.
13. Verfahren nach Anspruch 1 1 dadurch gekennzeichnet, dass eine Kombination von Antioxidantien verfüttert wird, ausgewählt aus der Gruppe bestehend aus: bestehend aus BHT (E321 ), BHA, Propylgallat (E310), Ethoxyquin (E324), Zitronensäure (E330), THBQ (E319) sowie Carnitin. 13. The method of claim 11, characterized in that a combination of antioxidants is fed, selected from the group consisting of: consisting of BHT (E321), BHA, propyl gallate (E310), ethoxyquin (E324), citric acid (E330), THBQ (E319) as well as carnitine.
14. Verfahren nach Anspruch 1 1 dadurch gekennzeichnet, dass dass es sich um Tiere handelt, ausgewählt aus der Gruppe, bestehend aus landwirtschaftlichen Nutztieren,14. The method according to claim 1 1, characterized in that they are animals selected from the group consisting of farm animals,
Wiederkäuern und Nichtwiederkäuern, Rindern, Kühen, Milchkühen, Ziegen, Ruminants and non-ruminants, cattle, cows, dairy cows, goats,
Milchziegen, Schafe, Milchschafe, Schweinen, Zuchtsauen, Geflügel, Mastgeflügel- und Legegeflügelelterntieren, Küken, Hühner, Puten, Gänsen, Enten, Pferden, besonders bestehend aus Wiederkäuern, insbesondere Rindern, Kühe, Milchkühe, Ziegen, Milchziegen, Schafe und Milchschafe, bevorzugt Milchkühe. Dairy goats, sheep, dairy sheep, pigs, sows, poultry, poultry and laying poultry, chicks, chickens, turkeys, geese, ducks, horses, especially ruminants, in particular cattle, cows, dairy cows, goats, milking goats, sheep and milk sheep Dairy cows.
2 2
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CN104824371A (en) * | 2015-04-10 | 2015-08-12 | 周建康 | Novel liquid antioxidant and preparation method thereof |
CN110810643A (en) * | 2019-12-17 | 2020-02-21 | 北京九州大地生物技术集团股份有限公司 | Feed for promoting milk yield of dairy sheep and preparation method and application thereof |
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EP2904911A1 (en) * | 2014-02-11 | 2015-08-12 | Evonik Degussa GmbH | Use of guanidinoacetic acid and/or creatine for increasing the hatching rate |
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Cited By (2)
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CN104824371A (en) * | 2015-04-10 | 2015-08-12 | 周建康 | Novel liquid antioxidant and preparation method thereof |
CN110810643A (en) * | 2019-12-17 | 2020-02-21 | 北京九州大地生物技术集团股份有限公司 | Feed for promoting milk yield of dairy sheep and preparation method and application thereof |
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