A novel animal feed additive composition

Abstract

The present invention relates to the use of an animal feed additive composition for control of undesired microbial growth, the composition comprising, glycerol ester selected from the group consisting of; mono-, di- and tripropionin, -butyrin, -valerin and mixtures thereof, vegetable oil, tannin, and / or saponins. The present invention also relates to the use of the animal feed additive for promoting intestine growth, alleviating or mitigating effects from necrotic enteritis, modulating gut flora and / or as an additive to drinking water.

Description

[0001] A novel animal feed additive composition

[0002] DESCRIPTION

[0003] The present invention refers to the use of a glycerol ester based composition of at least one short chain fatty acid, vegetable oil together with tannins and / or saponins for preventing, mitigating and / or alleviating necrotic enteritis in the gastric tract of animals.

[0004] Disruption of gut integrity and permeability contributes to enteritis which left untreated can become necrotic. Necrotic enteritis is an acute infection affecting galloanserans. Galloanserans are divided into the subgroups galliformes (landfowls) like chicken, turkey, grouse and pheasant, and anseriforms (waterfowls) like ducks, goose and swan. Necrotic enteritis has become an emerging problem especially among poultry and is characterized by severe necroses of intestinal mucosa. The clinical illness is usually very short and often the only signs are a sudden increase in mortality. However, birds with depression, ruffled feathers, and diarrhea may also be seen. The gross lesions are primarily found in the small intestine (jejunum), which may be ballooned, friable, and contain a foul-smelling, brown fluid.

[0005] Not only landfowls and waterfowls are affected by necrotic enteritis, also other farm animals such as, but not limited to, swine, bovine, goat, sheep, rabbit and horse.

[0006] Necrotic enteritis is known to affect also aquatic vertebrates such as from species such as salmon, catfish, carp, arctic char, trout, tilapia, eels, tuna, and invertebrates such as crabs, shrimp crayfish, mussels and oysters.

[0007] The causative agent is the gram-positive, obligate, anaerobic bacteria Clostridium perfringens. There are two primary C. perfringens types, A and C, associated with necrotic enteritis in galloanserans. Toxins produced by the bacteria cause damage to the small intestine, but also liver lesions, and mortality.

[0008] C. perfringens is a nearly ubiquitous bacteria readily found in soil, dust, feces, feed, and for example used poultry litter. It is also a normal inhabitant of the intestines of healthy galloanserans. Development of necrotic enteritis depends on the presence of predisposing factors, such as mucosal damage caused by pathogens and feed containing high protein levels.

[0009] Because C. perfringens is nearly ubiquitous, it is important to counteract changes in the intestinal microflora that would promote its growth. This has earlier been accomplished by routinely adding antibiotics to the feed. However, since the ban of growth promoting antibiotics in the European Union in 2006, necrotic enteritis has become an emerging disease among, for instance, poultry. There is a great need for alternative methods to counteract this disease or malfunction.

[0010] An alternative to counteracting harmful bacteria like C. perfringens through antibiotics is to try to balance or normalize the gut flora. The gut flora consists of a complex of microorganism species that live in the digestive tract. In this context gut is synonymous with intestinal and flora with microbiota and microflora. The microorganisms perform a host of useful functions, such as fermenting unused energy substrates, training the immune system, preventing growth of harmful, pathogenic bacteria, regulating the development of the gut, producing vitamins for the host and producing hormones to direct the host to store fats. However, in certain conditions, some species are thought to be capable of causing diseases or malfunction by producing infection or increasing cancer risk for the host.

[0011] The ailments described above is in some way related to demand for high productivity in farming for meat, milk and egg. Animals as listed above are provided with feed designed to increase productivity, be it muscle mass, milk or egg, which causes stress on intestine and an environment for microbial imbalance in said intestine. The problem is accordingly multifaceted, i.e. the need to avoid antibiotics, since overuse of this have and will continue to create antibiotic resistant bacteria. An animal with a healthy gastric tract, as well as a healthy microbiota in said gastric tract will also have a natural ability to have a natural defense against harmful microbiota.

[0012] The present invention discloses the use of a glycerol ester based composition for preventing and / or alleviating necrotic enteritis in the gastric tract of animals while at the same time enhance the gut health by improving the villus / crypt ratio together with creating an environment in the gastric tract beneficial to, what can be described as, a healthy gut flora. The use of said composition for modulating the gut flora of animals is also disclosed. Use of the composition according to the invention balances or normalizes the gut flora of animals in such a way that the growth of pathogenic species is inhibited and diseases like necrotic enteritis are prevented. One mechanism behind this effect is presently believed to be that the growth of helpful bacteria is favored and that this prevents the growth of pathogenic species by competing for nutrition and attachment sites to the epithelium of the colon.

[0013] The present invention further discloses the use of the glycerol ester based composition for use in drinking water for animals which is an important and often forgotten way to administer gut health enhancing and improving villus / crypt ratio.

[0014] The present invention relates to a novel mixed glycerol ester composition comprising short chain fatty acid glycerol ester molecules. The composition can be useful for mitigating moderate to severe gut health challenges in animals and, in particular, it has shown to be effective for mitigating and / or alleviating necrotic enteritis in poultry.

[0015] It is well known in the art that different short chain fatty acids have multiple positive effects both on animal gut health and performance in general as well as against specific pathogenic bacteria. Utilizing glycerol esters of short chain fatty acids is a technology to achieve the targeted delivery of these acids to the gastrointestinal tract of an animal. There are several advantages associated with delivering the said acids in the form of glycerol esters. Some of the acids, like propionic acid, butyric acid and valeric acid are either corrosive and / or have a pungent, unpleasant odor, which causes handling, safety, manufacturing and transport challenges. Said glycerol esters do not have these issues related to smell or corrosiveness. Delivering short chain fatty acids to an animal in the form of glycerol esters is also a good way to transport the fatty acids to the lower regions of the gastrointestinal tract of an animal. Free short chain fatty acids are likely to be adsorbed and / or disintegrated to a degree in the higher regions of the gastrointestinal canal and will reach the cecum or large intestine in far lower concentrations than intended for an effective dose. Glycerol esters on the other hand will to a large extent reach these regions in a partly dissociated form and a large proportion of the fatty acid will be released and adsorbed in these regions.

[0016] Glycerol esters of butyric acid are well known as feed additives because of their ability to improve animal performance and decrease the feed conversion ratio of animals. Further on, glycerol esters of different short chain fatty acids have been shown to inhibit different disease-causing bacteria. For example, it is known from EP3229605 that a glycerol ester composition comprising trivalerin inhibits gram-negative pathogens like Salmonella. Further on, EP3273797 discloses that a glycerol ester composition comprising monovalerin inhibits the gram-positive bacteria Clostridium perfringens, which causes necrotic enteritis in chicken.

[0017] The present invention has revealed a new type of animal feed additive composition, comprising glycerol ester, vegetable oil, tannins and / or saponins. This unique animal feed additive composition has indicated to be an effective tool for mitigating and alleviating moderate to severe gut health challenges in animals and to increase performance both in non-challenged and challenged animals. The animal feed additive composition according to the present invention can be useful for mitigating multifactorial gut health syndromes like necrotic enteritis.

[0018] Necrotic enteritis can be relatively asymptomatic, but young or immunocompromised animals may suffer severe symptoms and death.

[0019] While necrotic enteritis can infect a wide variety of animals, including humans, birds, and livestock, they are usually species-specific and do not spread between species.

[0020] Most knowledge on necrotic enteritis has been obtained from poultry, causing loss of several billion € yearly in commercial poultry production with tremendous economic impact. The economic significance of necrotic enteritis is attributed to decreased animal production (higher feed conversion, growth depression and increased mortality) and the costs involved in treatment and prevention.

[0021] The search for effective and more sustainable alternatives for mitigating gut health challenges in animals, like necrotic enteritis, has revealed a novel animal feed additive composition.

[0022] The invention accordingly relates, in a first aspect, to an animal feed additive composition characterized in that it comprises: a) 10-50 parts by weight, preferably 20-40 parts by weight, of a glycerol ester selected from the group consisting of: mono, di and tripropionin, mono, di and tributyrin, mono, di and trivalerin and mixtures thereof, and b) 1 -25 parts by weight, preferably 5-10 parts by weight, of an oil selected from the group consisting of: sunflower oil, rapeseed oil, peanut oil, soybean oil, corn oil, palm oil, olive oil and combinations thereof, and c) 0.3-8 parts by weight, preferably 0.4-2 parts by weight, of a tannin and / or a saponin, where said tannin preferably is an hydrolysable tannin such as a gallotannin, even more preferably a tannin from chestnut extract.

[0023] According to one embodiment of the invention, the animal feed composition further comprises 10 - 200 parts by weight, preferably 50 - 170 parts by weight, more preferably 100-160 parts by weight, of water.

[0024] According to one embodiment of the invention the animal feed additive composition further comprises 1 -5 parts by weight of caseinate.

[0025] According to one embodiment of the invention the animal feed additive composition further comprises 0.3 - 8 parts by weight of soy protein.

[0026] According to one embodiment of the invention the animal feed composition is in the form of an aqueous emulsion, preferably emulsified through mechanical micronization.

[0027] According to a preferred embodiment of the invention, the amount of glycerol ester a) and the amount of oil b) is calculated by density so that a)*n1 + b)*n2 = 1 ±0.05 where 1 is the density of water and n1 is the amount in % by weight of the glycerol ester and n2 is the amount in % by weight of oil.

[0028] The average droplet size of the glycerol ester and oil is preferably in the range 0.05 - 5 pm. It will accordingly through a careful calculation of the density, aiming as close as possible to the density of water, of the glycerol ester to oil blend. The micronization is suitably performed through ultrasonic treatment. The micronization is more preferably performed through high pressure homogenization.

[0029] According to a preferred embodiment of the invention, the oil in the animal feed composition is sunflower oil.

[0030] According to one embodiment of the invention the animal feed additive composition further comprises 0.5 - 5 part per weight of a metal formate, acetate, propionate or combinations thereof and wherein the metal is selected from the group consisting of: sodium, potassium and calcium. The pH in the animal feed additive is advantageously adjusted to pH in the range 6 - 7.

[0031] According to one embodiment of the invention the animal feed additive composition further comprises 1 % by weight of potassium sorbate. This can suitably be added having a function as a preservative. It is advantageous to also add an antioxidant to avoid discoloration as potassium sorbate is known to oxidize adding a yellow or brown tone to the composition it is added to.

[0032] The animal feed additive composition is according to one embodiment of the invention administered to the animal feed to an amount of 0.2 - 0.8 gram per kilogram of feed, suitably to an amount of 0.4 - 0.6 gram per kilogram of feed.

[0033] According to a particularly suitable embodiment of the invention the animal feed additive composition is administered to the animal drinking water, preferably to an amount of 0.1 - 0.5 gram per liter of water. According to a preferred embodiment of the invention the animal feed additive composition is administered to the animal drinking water to an amount of 0.15 - 0.3 gram per liter of water.

[0034] The animal feed additive composition is advantageous for adding to drinking water, which is an often forgotten way to administer feed additives.

[0035] It also opens up for alternative ways to process so called TMR (total mixed rations) and other type of readily made animal feed products like feed pellets.

[0036] The animal feed additive composition may accordingly be added to drinking water or used in the preparation of feed pellets, TMR (total mixed ration) or the like for a landfowl including a chicken, a turkey, a grouse or a pheasant, a waterfowl including a duck, a goose or a swan, a swine, a bovine, a goat, a sheep, a rabbit and a horse; preferably for a chicken or a turkey.

[0037] In a further aspect, the invention also relates to a use where the animal feed additive composition is administered via the solid feed in aquafarming. It may accordingly be used in the preparation of feed pellets used in the aquafarming of aquatic vertebrates such as from species such as salmon, catfish, carp, arctic char, trout, tilapia, eels, tuna, and also invertebrates such as crabs, shrimp, crayfish. A typical inmix of the animal feed additive composition of the present invention shall then be in the range 0.2 - 0.8 gram per kilogram of feed, preferably 0.4 - 0.6 gram per kilogram of feed.

[0038] In a further aspect, the present invention relates also to the animal feed additive composition according to the present invention for use in the prevention, mitigation and / or alleviation of necrotic enteritis in the gastric tract of an animal.

[0039] In other words, according to this further aspect the present invention relates to a method for preventing, mitigating and / or alleviating necrotic enteritis in the gastric tract of an animal comprising the step of administering the animal feed additive composition according to the first aspect of the present invention to said animal.

[0040] Preferably, said animal is a landfowl, including a chicken, a turkey, a grouse or a pheasant, a waterfowl, including a duck, a goose or a swan, a swine, a bovine, a goat, a sheep, a rabbit, or an horse, more preferably a chicken or a turkey, when the animal feed additive composition is administered adding it to drinking water or used in the preparation of feed pellets, TMR (total mixed ration) or the like.

[0041] Preferably, said animal is an aquatic vertebrate such as from species such as salmon, catfish, carp, arctic char, trout, tilapia, eels, or tuna, or an aquatic invertebrate such as a crab, a shrimp, or a crayfish, when the animal feed additive composition is administered via the solid feed in aquafarming.

[0042] In a still further aspect, the present invention relates also to the animal feed additive composition according to the present invention for a use selected from the group consisting of:

[0043] - control of undesired microbial growth,

[0044] - an intestine growth promotor,

[0045] - alleviating or mitigating effects from necrotic enteritis,

[0046] - a gut flora modulator,

[0047] - an additive to drinking water.

[0048] In a still further aspect, the present invention relates to an aqueous emulsion comprising the animal feed additive composition according to the first aspect of the invention.

[0049] In one embodiment of the invention, said aqueous emulsion is prepared through mechanical micronization.

[0050] Maintaining a strong gut health is important for all animal, in order to be able to manage different gut health challenges like bacteria, parasites and viruses. Some of the most challenging diseases among animals are so called multifactorial gut health syndromes, like necrotic enteritis. The animal feed additive composition according to the present invention can be useful for mitigating such multifactorial gut health syndromes in animals. According to another embodiment, the present invention refers to the use of said feed additive for improving the feed conversion ratio of animals.

[0051] EMBODIMENT EXAMPLES

[0052] The present invention is illustrated in the below Embodiment Examples, which is to be construed as merely illustrative and not limiting in any way.

[0053] - Example 1a - d discloses a method and compositions for manufacturing a stabile waterborne emulsion of the composition according to the invention.

[0054] - Example 2 disclose results from a field study.

[0055] Example 1a

[0056] 75 parts per weight of tributyrin were mixed with 25 parts per weight of sunflower oil. This mix was then mixed with 5 parts per weight of tannin from chestnut extract and 1 .5 parts per weight of caseinate. The composition thus obtained was then mixed with 150 parts per weight of water and thus it was then micronized utilizing ultrasonic mixing.

[0057] Example 1 b

[0058] 85 parts per weight of a glycerol-mono-butyrin I glycerol-di-butyrin mixture were mixed with 15 parts per weight of sunflower oil. This mix was then mixed with 5 parts per weight of tannin from chestnut extract and 1 .5 parts per weight of caseinate. The composition thus obtained was then mixed with 150 parts per weight of water and thus it was the micronized utilizing ultrasonic mixing.

[0059] Example 1c

[0060] 95 parts per weight of glycerol-trivalerin were mixed with 5 parts per weight of sunflower oil. This mix was then mixed with 5 parts per weight of tannin from chestnut extract and 1 .5 parts per weight of caseinate. The composition thus obtained was then mixed with 150 parts per weight of water and thus it was the micronized utilizing ultrasonic mixing.

[0061] Example 1d

[0062] 75 parts per weight of a glycerol-mono-valerin I gycerol-tri-valerin mixture were mixed with 25 parts per weight of sunflower oil. This mix was then mixed with 5 parts per weight of tannin from chestnut extract and 1 .5 parts per weight of caseinate. The composition thus obtained was then mixed with 150 parts per weight of water and thus it was the micronized utilizing ultrasonic mixing.

[0063] The average droplet size where analyzed after two days of storage in room temperature and was in all examples 1 a - 1 d above found to be in the range 0.1 - 2pm. All examples where found to be stable over time with no separation into a visible oil and water phase, i.e. no sedimentation was detectable.

[0064] Example 2

[0065] A Randomized Complete Block Design (RCBD) with 3 experimental treatments was used to test the feed composition on chickens. Treatments were balanced by initial weight. All the chickens were vaccinated against coccidia with Evant® (Hipra) orally by spray at 1 day of life (Eimeria acervulina, Eimeria maxima, Eimeria mitis, Eimeria praecox, and Eimeria tenella) using an overdose (10x the recommended dose) and used litter from other batches was added, after being analyzed in order to create a biological challenge.

[0066] Treatment

[0067] T1 Negative Control Control (C)

[0068] T2 Positive Control C + coccidiostat (Montebari™)

[0069] T3 The composition according to Example 1 c of the present invention, dosage 250 mg / L of drinking water.

[0070] Number of treatments: 6 Animals per replicate: 20 Replicates per treatment: 10 Animals per treatment:

[0071] All birds were provided with the same balanced and traditional diet adapted to age, i.e. starter diet 0-7 days, grower diet 8 - 21 days and finisher diet 22 - 42 days. All birds had free access to drinking water but only the test group T3 had access to drinking water containing 250 mg I liter of the composition according to the present invention.

[0072] The birds were analyzed for lesions in the gastric tract after the test period

[0073] TMLS: Total Mean Lesion Score. Values indicated are the mean values for the 10 replicates (measured in 3 broilers). Values range from 0 to 6. The T1 group (control) had a TMLS of 2.7 while the group T2 receiving a coccidiostat had a TMLS of 2.8. The group T3 receiving treatment according to the invention had the lowest TMLS at only 1 .1 and accordingly performed best of the three groups.

Claims

CLAIMS1 . An animal feed additive composition characterized in, that it comprises: a) 10-50 parts by weight of a glycerol ester selected from the group consisting of; mono, di and tripropionin, mono, di and tributyrin, mono, di and trivalerin and mixtures thereof, and b) 1 -25 parts by weight of an oil selected from the group consisting of: sunflower oil, rapeseed oil, peanut oil, soybean oil, corn oil, palm oil, olive oil and combinations thereof, and c) 0.3-8 parts by weight of a tannin and / or a saponin.

2. The animal feed additive composition according to claim 1 , wherein it further comprises 1 -5 parts by weight of caseinate.

3. The animal feed additive composition according to claim 1 or 2, wherein it further comprises 0.3-8 parts by weight of soy protein.

4. The animal feed additive composition according to any of claims 1 - 3, wherein the amount of glycerol ester a) and the amount of oil b) is calculated by density so that a)*n1 + b)*n2 = 1 ±0.05 where 1 is the density of water and n1 is the amount in % by weight of the glycerol ester and n2 is the amount in % by weight of oil.

5. The animal feed additive composition according to claim 3 or 4, wherein an average droplet size of the glycerol ester and oil is in the range 0.05 - 5 pm.

6. The animal feed additive composition according to any of claims 1 - 5, wherein the animal feed additive composition further comprises 0.5 - 5 part per weight of a metal formate, acetate, propionate or combinations thereof and wherein the metal is selected from the group consisting of: sodium, potassium and calcium.

7. The animal feed additive composition according any of the claims 1 - 6, wherein the pH in the animal feed additive is in the range 6 - 7.

8. The animal feed additive composition according to any of the claims 1 - 7, wherein the animal feed additive composition is administered to the animal feed to an amount of 0.2 - 0.8 gram per kilogram of feed.

9. The animal feed additive composition according to claim 8, wherein the animal feed additive composition is administered to the animal feed to an amount of 0.4 - 0.6 gram per kilogram of feed.

10. The animal feed additive composition according to any of the claims 1 - 9 wherein the animal feed additive composition is administered to the animal drinking water, preferably to an amount of 0.1 - 0.5 gram per liter of water.1 1. The animal feed additive composition according to claim 10 wherein the animal feed additive composition is to an amount of 0.15 - 0.3 gram per liter of water.

12. The animal feed additive composition according to any of the claims 1 - 9 wherein the animal feed additive composition is administered via the solid feed in aquafarming.

13. The animal feed additive composition according to any of claims 1 - 12, for use in the prevention, mitigation and / or alleviation of necrotic enteritis in the gastric tract of animals.

14. The animal feed additive composition according to any of claims 1 - 12, for an use selected from the group consisting of:- control of undesired microbial growth,- an intestine growth promotor,- alleviating or mitigating effects from necrotic enteritis,- a gut flora modulator,- an additive to drinking water.

15. An aqueous emulsion comprising the animal feed additive composition according to any of claims 1 - 7.

16. The aqueous emulsion according to claim 15, wherein said aqueous emulsion is prepared through mechanical micronization.