阅读说明：本技术 动物饲料材料 (Animal feed material ) 是由 蒂姆·古森斯 菲利普·弗洛里蒙德·马格达莱纳·范·梅里塞尔 勒内·克瓦克尔 皮埃尔·克莱门特· 于 2018-12-20 设计创作，主要内容包括：本发明涉及家畜动物饲料领域,尤其涉及一种有效预防和/或治疗家畜致病性感染和/或提高家畜生产效率的饲料材料。已经发现,将多糖丁酰酯经肠施用于家畜动物会导致下肠道中丁酸盐浓度增加。与其他丁酸盐制剂或产品相比,这导致了下肠道和粪便中病原体的减少和更好的生长性能结果。因此,本发明提供了新型多糖丁酰酯、包含所述多糖丁酰酯的组合物(例如饲料添加剂和/或饲料),以及所述多糖丁酰酯作为饲料添加剂的用途(例如用于预防或治疗家畜的病原性感染和/或提高家畜生产的效率)。(The invention relates to the field of livestock animal feed, in particular to a feed material which is effective in preventing and/or treating livestock pathogenic infection and/or improving livestock production efficiency. It has been found that enteral administration of the polysaccharide butyryl ester to livestock animals results in an increased concentration of butyrate in the lower intestinal tract. This results in a reduction of pathogens in the lower intestinal tract and faeces and better growth performance results compared to other butyrate formulations or products. Accordingly, the present invention provides novel polysaccharide butyryl esters, compositions (e.g., feed additives and/or feedstuffs) comprising the polysaccharide butyryl esters, and uses of the polysaccharide butyryl esters as feed additives (e.g., for preventing or treating pathogenic infections in livestock and/or increasing the efficiency of livestock production).)

1. A feed grade composition comprising a cellulose butyryl ester, said cellulose butyryl ester further comprising an acetyl ester group, wherein said cellulose butyryl ester is characterized by a number average molar mass of 1000000g/mol, preferably 5000-500000g/mol, preferably 7000-250000g/mol, preferably 10000-100000g/mol, preferably 12000-50000g/mol, preferably 13000-25000g/mol, most preferably 15000-17000 g/mol.

2. A composition according to claim 1, wherein the average number of butyryl groups per monosaccharide unit is in the range of 0.1-4, preferably 1-3.5, preferably 1.75-3.25, preferably 2.25-3, preferably 2.5-2.95.

3. The composition according to any of the preceding claims, wherein the cellulose butyryl ester is characterized by an acetyl content of at least 1 wt.%, preferably at least 2 wt.%, preferably at least 3 wt.%, preferably at least 4 wt.%, of the total weight of cellulose butyryl ester.

4. The composition according to any one of the preceding claims, which is a feed material comprising 0.1-80 wt.%, preferably 0.5-60 wt.%, preferably 1-50 wt.%, preferably 2-40 wt.%, preferably 3-30 wt.%, preferably 4-20 wt.%, preferably 5-15 wt.% cellulose butyrate and one or more other feed grade materials.

5. The composition of claim 4, wherein the other ingredient is selected from the group consisting of: technical additives, sensory additives, nutritional additives, animal technical additives, anticoccidial agents and tissue stabilizers.

6. A composition according to any one of claims 1-3, which is an animal feed composition comprising 0.0001-10 wt.% cellulose butyryl ester, preferably 0.001-5 wt.%, preferably 0.005-1 wt.%, preferably 0.0075-0.5 wt.%, preferably 0.01-0.1 wt.% cellulose butyryl ester, and one or more animal feed ingredients.

7. The composition of any one of the preceding claims, in the form of a powder.

8. The composition of any one of claims 1-6, in the form of a compressed dose, granules, or pellets.

9. The composition according to claim 8, wherein cellulose butyryl ester is uniformly distributed in the primary particles constituting the composition.

10. A cellulose butanoate, which further comprises an acetyl ester group, wherein the cellulose butanoate is characterized by a number average molar mass of 1000000g/mol, preferably 500000g/mol, preferably 7000 250000g/mol, preferably 10000-100000g/mol, preferably 12000-50000g/mol, preferably 13000-25000g/mol, most preferably 15000-17000g/mol, for use in a method of treatment for prophylaxis or therapy.

11. A cellulose butyryl ester further comprising an acetyl ester group, wherein the cellulose butyryl ester is characterized by a number average molar mass of 1000000g/mol, preferably 5000-500000g/mol, preferably 7000-250000g/mol, preferably 10000-100000g/mol, preferably 12000-50000g/mol, preferably 13000-25000g/mol, most preferably 15000-17000g/mol, for preventing or treating a pathogen infection, preferably an infection of one or more of a bacterium, eimeria, virus and fungus, preferably a bacterium, preferably Clostridium acetobutylicum (Clostridium acetobutylicum), Escherichia coli (Escherichia coli), streptococcus cremoris (streptococcus cremoris), Lactococcus lactis (Lactococcus cremoris), Lactococcus cremoris (Lactococcus cremoris), Clostridium perfringens (Clostridium perfringens), Campylobacter jejuni (Campylobacter) One or more of Campylobacter coli (Campylobacter coli), Lawsonia intracellularis (Lawsonia intracellularis), Brachyspira hyodysenteriae (Brachyspira hyodysenteriae), Enterococcus ceaeae (Enterococcus caecorum), Streptococcus suis (Streptococcus suis), and Salmonella enteritidis (Salmonella enteritidis).

12. A cellulose butyryl ester further comprising acetyl ester groups, wherein the cellulose butyryl ester is characterized by a number average molar mass of 1000000g/mol, preferably 5000-500000g/mol, preferably 7000-250000g/mol, preferably 10000-100000g/mol, preferably 12000-50000g/mol, preferably 13000-25000g/mol, most preferably 15000-17000g/mol, for improving the intestinal flora.

13. A composition according to any one of claims 10 to 12, wherein the average number of butyryl groups per monosaccharide unit is in the range 0.1 to 4, preferably 1 to 3.5, preferably 1.75 to 3.25, preferably 2.25 to 3, preferably 2.5 to 2.95.

14. Use of a composition according to any one of claims 10-13, wherein the polysaccharide butyryl ester is characterized by an acetyl content of at least 1 wt.%, preferably at least 2 wt.%, preferably at least 3 wt.%, preferably at least 4 wt.%, based on the total weight of the polysaccharide butyryl ester.

15. A non-therapeutic method for

The conversion rate of the feed is reduced,

increase the weight of the living body, or

Increase the average daily gain of the plant,

comprising applying a cellulose butyryl ester, said cellulose butyryl ester further comprising an acetyl ester group, wherein said cellulose butyryl ester is characterized by a number average molar mass of 1000000g/mol, preferably of 5000-500000g/mol, preferably of 7000-250000g/mol, preferably of 10000-100000g/mol, preferably of 12000-50000g/mol, preferably of 13000-25000g/mol, most preferably of 15000-17000 g/mol.

16. The non-therapeutic method according to claim 15, wherein the average number of butyryl groups per monosaccharide unit is in the range of 0.1-4, preferably 1-3.5, preferably 1.75-3.25, preferably 2.25-3, preferably 2.5-2.95.

17. The non-therapeutic method according to claim 15 or 16, wherein the polysaccharide butyryl ester is characterized by an acetyl content of at least 1 wt.%, preferably at least 2 wt.%, preferably at least 3 wt.%, preferably at least 4 wt.%, based on the total weight of cellulose butyryl ester.

18. The composition for use according to any one of claims 10-14, wherein the animal to be treated is a poultry species.

19. The non-therapeutic method of any one of claims 15-17, wherein the animal to be treated is a poultry species.

20. Use of a cellulose butanoate, which further comprises an acetyl ester group, or of a composition according to any of claims 1 to 9 in animal feed, wherein the cellulose butanoate is characterized by a number average molar mass of 2000-1000000g/mol, preferably 5000-500000g/mol, preferably 7000-250000g/mol, preferably 10000-100000g/mol, preferably 12000-50000g/mol, preferably 13000-25000g/mol, most preferably 15000-17000 g/mol.

21. Use according to claim 20, wherein the average number of butyryl groups per monosaccharide unit is in the range of 0.1-4, preferably 1-3.5, preferably 1.75-3.25, preferably 2.25-3, preferably 2.5-2.95.

22. Use according to claim 20 or 21, wherein the polysaccharide butyryl ester is characterized by an acetyl group content of at least 1 wt.%, preferably at least 2 wt.%, preferably at least 3 wt.%, preferably at least 4 wt.%, based on the total weight of the cellulose butyryl ester.

23. A method of preparing an animal feed composition, the method comprising:

providing a first animal feed component,

providing a cellulose butyryl ester further comprising an acetyl ester group, wherein the cellulose butyryl ester is characterized by a number average molar mass of 1000000g/mol, preferably of 5000-500000g/mol, preferably of 7000-250000g/mol, preferably of 10000-100000g/mol, preferably of 12000-50000g/mol, preferably of 13000-25000g/mol, most preferably of 15000-17000g/mol, and

mixing the first animal feed component with cellulose butyryl ester to a homogeneous mixture.

24. The method according to claim 23, wherein the average number of butyryl groups per monosaccharide unit is in the range of 0.1-4, preferably 1-3.5, preferably 1.75-3.25, preferably 2.25-3, preferably 2.5-2.95.

25. The method according to claim 23 or 24, wherein the cellulose butyryl ester is characterized by an acetyl content of at least 1 wt.%, preferably at least 2 wt.%, preferably at least 3 wt.%, preferably at least 4 wt.%, based on the total weight of cellulose butyryl ester.

Technical Field

The invention relates to the field of livestock animal feed, in particular to a feed material which is effective in preventing and/or treating livestock pathogenic infection and/or improving livestock production efficiency.

Background

The increasing global demand for animal products requires new strategies to improve the efficiency of animal product production. Optimization of nutrient utilization is an essential element of these strategies. Consumer and government concerns about food safety, reducing environmental impact, improving animal welfare, and careful use of antibacterial drugs have created additional demands on animal husbandry.

One area of particular interest in animal husbandry is the elimination of pathogens, such as Salmonella (Salmonella) and other pathogenic bacteria. Salmonella is one of the most important causes of food-borne infections in humans, mainly due to consumption of poultry or contaminated eggs. The agricultural sector attempts to reduce the number of salmonella infections by different measures, such as vaccination, intensive hygiene measures and/or administration of antibiotics, probiotics, acidifiers or short and medium chain fatty acids and salts thereof.

In recent years, the bacteriostatic action of volatile short-chain fatty acids on gram-negative bacteria has attracted attention. The volatile short-chain fatty acid is composed of biodegradable weak organic acid, and can eliminate pathogenic microorganisms without significantly affecting intestinal flora. It has been demonstrated that volatile short chain fatty acids can inhibit the growth of haemolytic strains of E.coli (Escherichia coli) by 50%. Many short chain fatty acid compositions have been developed for use as feed additives to achieve pathogen reduction in animals.

EP1354520 describes a feed additive and its preparation by spray cooling, which is a microcapsule comprising n-butyric acid in a matrix comprising a lipid structure (wax). According to EP1354520, microencapsulation of butyric acid is particularly helpful to combat the difficulties associated with the volatility and rancid smell of butyric acid, which creates difficulties in handling as a feed additive. The formulation is also shown to be stable to gastric degradation in EP 1354520.

Van Immerseel et al (2005Poultry Science 84:1851-1856) compared the effect of butyric acid as a Poultry feed additive with butyric acid embedded in a fat matrix. They reported that in the group to which butyric acid embedded in the fat matrix was administered, colonization of the cecum by salmonella and fecal shedding of salmonella was significantly reduced.

WO2007/124949 describes the use of 3-hydroxybutyrate and poly-3-hydroxybutyrate compounds as feed additives.

BE1023491 describes a feed additive comprising butyric acid in a wax matrix comprising microcrystalline wax and its production by melt extrusion.

It is an object of the present invention to provide an animal feed additive having an improved effect in the prevention or treatment of pathogenic infections in livestock and/or in the improvement of the efficiency of livestock production.

Disclosure of Invention

The present inventors have surprisingly found that these objects can be achieved with certain esters of a polysaccharide and butyric acid.

It has been found that enteral administration of the polysaccharide butyryl ester of the invention to a livestock animal results in an increased concentration of butyrate in the lower intestinal tract. The inventors hypothesized that this correlates with the effectiveness of the butyryl ester polysaccharide in the presence of pathogenicity in the lower intestine and feces observed in vivo tests. It was also surprisingly found that administration of the polysaccharide butyryl ester resulted in better growth performance results compared to other butyrate formulations or products. The polysaccharide butyryl ester according to the invention provides a very desirable combination of improved Average Daily Gain (ADG) and Average Daily Feed Intake (ADFI) with reduced Feed Conversion Ratio (FCR) and mortality during the refeeding period, and shows no adverse effects during the slaughtering period.

Butyric acid is believed to stimulate the growth of intestinal villi and/or alter the development of gastrointestinal microorganisms. Butyric acid is also thought to down-regulate the expression of genes involved in salmonella invasion at low doses. Other benefits contemplated by the inventors when using the polysaccharide butyryl composition of the invention may include improved retention of intestinal contents in the small intestine, improved digestion/absorption of methionine and/or a more diverse microbial population in the lower gastrointestinal tract.

The source of the increased concentration of butyric acid may be a prebiotic effect (such as, but not limited to, a prebiotic effect on butyric acid producing bacteria), direct release of butyric acid resulting from degradation of the polysaccharide butyryl ester, any other mechanism resulting in an increased concentration of butyric acid, or a combination thereof. Without wishing to be bound by any theory, the inventors believe that the effect observed on the polysaccharide butyryl ester of the invention may also be related to the presence of more microorganisms capable of polysaccharide fermentation in the lower gastrointestinal tract than in the upper gastrointestinal tract.

Accordingly, the present invention provides novel polysaccharide butyryl esters, compositions (e.g., feed additives and/or feedstuffs) comprising the polysaccharide butyryl esters, and uses of the polysaccharide butyryl esters as feed additives (e.g., for preventing or treating pathogenic infections in livestock and/or increasing the efficiency of livestock production).

These and other aspects of the invention will become apparent from the following detailed description and the accompanying examples.

Drawings

FIG. 1: example 1-measured butyrate concentration in ileal inocula.

FIG. 2: example 1-measured butyrate concentration in colonic inoculum.

FIG. 3: example 1-measured butyrate concentration in cecal inocula.

FIG. 4: example 2-measured butyrate concentration in colon.

Detailed Description

A first aspect of the invention relates to a feed grade composition comprising the polysaccharide butyryl ester.

Butyric acid is a volatile short-chain aliphatic monocarboxylic acid with a molecular formula of CH₃-CH₂-CH₂-COOH. As used herein, the terms "butyric acid" and "butyrate" are used interchangeably and should be interpreted to mean the protonated (acid, butyric acid) and deprotonated (conjugate base, butyrate) forms, respectively. Those skilled in the art will appreciate that this is becauseButyric acid is a weak acid, which, when dissolved in an aqueous medium, is usually present in protonated and deprotonated forms, the concentration of each depending on the ph of the medium. The acid form can be absorbed by the intestinal wall and the cell membrane of the microorganism.

As used herein, the term "polysaccharide butyryl ester" refers to a compound known as a compound comprising a polysaccharide molecule as a central moiety, the polysaccharide molecule being derivatized/substituted with a plurality of butyric acid molecules by forming ester bonds between the carboxylic acid moiety of the butyric acid molecule and the hydroxyl groups of the polysaccharide.

As used herein, the term "polysaccharide" refers to a polymer comprising a backbone comprising monosaccharide repeating units and/or derivatized monosaccharide repeating units, typically cyclic pentose (particularly C) sugars ₅Aldose or ketose), or cyclic hexose (especially C)₆Aldose or ketose). C₅-C₆Non-limiting examples of aldoses include allose, altrose, glucose, mannose, gulose, idose, galactose, talose, ribose, arabinose, xylose, lyxose. C₅-C₆Non-limiting examples of ketoses include ribulose, xylulose, fructose, sorbose, and tagatose. As used herein, the term "monosaccharide derivative" refers to any chemically or enzymatically modified monosaccharide unit.

The polysaccharide may be a homopolysaccharide or a heteropolysaccharide, preferably a homopolysaccharide.

The polysaccharide may be modified or unmodified. In a preferred embodiment of the present invention, there is provided a polysaccharide butyryl ester, wherein the polysaccharide is selected from the group consisting of: starch, modified starch, amylopectin, modified amylopectin, amylose, modified amylose, chitosan, chitin, guar gum, modified guar gum, locust bean gum, tara gum, konjac flour, fenugreek gum, aloe mannan, modified cellulose, oxidized polysaccharide, sulfated polysaccharide, cationic polysaccharide, gum arabic, karaya gum, xanthan gum, kappa, iota or lambda carrageenan, agar, alginate, callose, laminarin, xylan, mannan, galactomannan, hemicellulose, pectin, arabinoxylan, xanthan gum, aspergillus niger polysaccharide, allopatry polysaccharide, laminarin, lichenin, glycogen, pullulan, dextran, umbilican, inulin, fructan, carrageenan, galactose, furcellaran, fucoidan, agarose, chitosan, guar gum, carrageenan, guar gum, porphyran, alginic acid, cutin sulfate, chondroitin sulfate, heparin and cellulose, preferably selected from the group consisting of: hemicellulose, starch and cellulose, most preferably the polysaccharide is cellulose.

In a preferred embodiment of the present invention, there is provided a polysaccharide butyryl ester, wherein the polysaccharide is selected from the group consisting of: a water-insoluble polysaccharide.

For the purpose of the present invention, the polysaccharide butyryl ester can be formed chemically, enzymatically, fermentatively by biosynthesis of natural or genetically modified organisms and the like. Typically, according to the present invention, the polysaccharide butyryl ester is produced by esterification (e.g., acid-catalyzed esterification) of a polysaccharide.

The number of substituents on the (anhydro) monosaccharide units of the polysaccharide can be expressed in terms of weight percent or the average number of substituents attached to the ring, a concept known to polysaccharide chemists as "degree of substitution" (d.s.). At C₆In the case of monosaccharides, if all three available positions on each unit are substituted, then d.s. is designated 3; if on average two are substituted on each ring, the d.s. is designated as 2, and so on. Similarly, the number of substituents on the polysaccharide can be expressed as a percentage of available positions for substitution.

In one embodiment of the present invention, the average number of butyryl groups per monosaccharide unit (d.s.) of the polysaccharide butyryl ester is in the range of 0.1 to 4. For example, according to the embodiments, the d.s. may be at least 0.25, at least 0.5, at least 0.75, at least 1.0, at least 1.25, at least 1.5, at least 1.75, at least 2.0, at least 2.25, or at least 2.5, and/or it may be less than 3.75, less than 3.5, less than 3.25, or less than 3. In exemplary embodiments, the d.s. is in the range of 0.5 to 3.5, in the range of 1.0 to 3.25, in the range of 1.5 to 3, or in the range of 2.0 to 2.95.

In a particularly preferred embodiment of the invention, the polysaccharide butyryl ester is a cellulose butyryl ester having an average number of butyryl groups per monosaccharide unit in the range of from 0.1 to 4, preferably from 1 to 3.5, preferably from 1.75 to 3.25, preferably from 2.25 to 3, preferably from 2.5 to 2.95.

In other embodiments, the polysaccharide butyryl ester has a butyryl content of at least 5 wt.% of the polysaccharide butyryl ester by weight, preferably at least 10 wt.%, at least 15 wt.%, at least 20 wt.%, at least 25 wt.%, at least 30 wt.%, at least 35 wt.%, at least 40 wt.%, at least 45 wt.%, at least 50 wt.%, or at least 55 wt.%. In an embodiment of the invention, the polysaccharide butyryl ester is a cellulose butyryl ester, characterized by a butyryl content in the range of 5-80 wt.% polysaccharide butyryl ester by weight, preferably 25-70 wt.%, 40-60 wt.%, or 50-56 wt.%.

In other embodiments, the butyryl ester of the polysaccharide has a butyryl content (expressed as a percentage of available polysaccharide hydroxyl groups that are substituted) of at least 5%, preferably at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, or at least 55%. In other embodiments, the butyryl content of the polysaccharide butyryl ester (expressed as a percentage of available polysaccharide hydroxyl groups that are substituted) results in a degree of substitution of 100% or less, e.g., less than 99%, less than 98%, less than 97%, less than 95%, less than 90%, less than 85%, less than 80%, or less than 75%.

In an embodiment of the invention, the polysaccharide butyryl ester is a cellulose butyryl ester characterized by a butyryl content (expressed as a percentage of available polysaccharide hydroxyl groups substituted) in the range of 5-80%, preferably 25-70%, 40-60%, or 50-56%.

In other preferred embodiments, the polysaccharide butyryl ester according to the present invention further comprises an acetyl ester group. In an embodiment of the invention, the polysaccharide butyryl ester comprises butyryl and acetyl groups, the molar ratio of butyryl to acetyl groups being at least 1/1, preferably at least 1.5/1, at least 2/1, at least 2.5/1, at least 3/1, at least 3.5/1, at least 4/1, at least 5/1, at least 6/1, at least 7/1, at least 8/1, at least 9/1, or at least 10/1. In an embodiment of the invention, the polysaccharide butyryl ester comprises butyryl and acetyl groups, the molar ratio of butyryl to acetyl groups being less than 100/1, preferably less than 75/1, less than 50/1, less than 40/1, less than 30/1, less than 25/1, less than 20/1, or less than 15/1. In an embodiment of the invention, the polysaccharide butyryl ester comprises acetyl groups and is characterized by a polysaccharide butyryl ester having an acetyl group content of at least 1 wt.%, preferably at least 2 wt.%, preferably at least 3 wt.%. In an embodiment of the invention, the polysaccharide butyryl ester comprises acetyl groups and is characterized by a polysaccharide butyryl ester having an acetyl group content of at most 10 wt.%, preferably at most 8 wt.%, preferably at most 5 wt.%.

According to the invention, the polysaccharide butyryl ester is a cellulose butyryl ester, characterized in that the acetyl content is in the range of 0.1-60 wt.% of cellulose butyryl ester, preferably 0.5-45 wt.%, preferably 1-30 wt.%, preferably 2-15 wt.%, preferably 3-10 wt.%, preferably 4-6 wt.%.

In an embodiment of the invention, the polysaccharide butyryl ester has a number average molar mass (M)_n) May be in the range of 2,000-1,000,000g/mol, preferably in the range of 5,000-500,000g/mol, 7,000-250,000g/mol, 10,000-100,000g/mol, 12,000-50,000g/mol, 13,000-25,000g/mol, or 15,000-17,000 g/mol. In an embodiment of the invention, the polysaccharide butyryl ester is characterized by a number average molar mass (M)_n) At least 2,000g/mol, preferably at least 4,000g/mol, preferably at least 8,000g/mol, preferably at least 12,000 g/mol. Furthermore, in an embodiment of the invention, the polysaccharide butyryl ester is characterized by a number average molar mass (M)_n) Less than 1,000,000g/mol, preferably less than 500,000g/mol, preferably less than 250,000g/mol, preferably less than 100,000g/mol, preferably less than 70,000g/mol, preferably less than 65,000g/mol, preferably less than 30,000g/mol, preferably less than 25,000g/mol, preferably less than 17,000 g/mol. The number average molar mass (M) _n) Can be determined by suitable methods known to the person skilled in the art, such as, for example, permeation, static light scattering, sedimentation equilibrium, gel permeation chromatography, viscometry, sedimentation velocity, dynamic light scattering, end group compositionAnd (6) performing precipitation and the like. Determination of the number-average molar mass (M)_n) The preferred method of (3) is gel permeation chromatography.

According to the invention, the composition comprising the polysaccharide butyryl ester is a feed grade composition. As used herein, the term "feed grade" refers to a food suitable for consumption by an animal, particularly livestock. In one embodiment, this means that the composition has been determined to be safe, functional and suitable for its intended use in animal food. For example, it is suitably treated and labeled, and/or complies with the appropriate regulations in the relevant jurisdictions regarding the use of the composition in animal food.

In an embodiment of the invention, the feed-grade composition comprises at least one further ingredient selected from the group consisting of: feed additives, feed grade formulation aids or excipients, and nutritional ingredients.

It will be appreciated that the choice and (relative) amounts of such additional ingredients will depend on the precise form and use of the feed grade composition. Embodiments are contemplated wherein the feed-grade composition is a feed additive or feed material. Embodiments are also contemplated wherein the feed grade composition is a feed premix or ready to use feed or forage. Unless otherwise indicated, the terms "feed additive" and "feed material" are used interchangeably herein and generally refer to a composition containing a high concentration of the polysaccharide butyryl ester, the composition being designed and prepared for mixing with feed or forage to provide a sufficient amount/dosage of the polysaccharide butyryl ester. It should be understood that these terms herein do not refer to the legal definitions used in animal feed regulations, which may vary between jurisdictions and/or change over time. Notwithstanding the former, it should be understood that the feed-grade compositions of the present invention may be provided in the form of a qualified feed additive or feed material in a strict legal (i.e., regulatory) sense.

In an embodiment of the invention, the feed grade composition is a feed material comprising the polysaccharide butyryl ester in combination with at least one other feed grade material. In an embodiment of the invention, a feed material is provided comprising 0.1-80 wt.%, preferably 0.5-60 wt.%, 1-50 wt.%, 2-40 wt.%, 3-30 wt.%, 4-20 wt.%, 5-15 wt.% of the polysaccharide butyryl ester and one or more other feed grade substances.

In an embodiment of the invention there is provided a feed material as defined herein, wherein the at least one other feed grade material is selected from the group consisting of: technical additives, sensory additives, nutritional additives, animal technical additives, anticoccidial agents and tissue stabilizers.

Examples of technical additives suitable for combination with the polysaccharide butyryl ester of the present invention include preservatives, antioxidants, emulsifiers, stabilizers, thickeners, gelling agents, binders, substances for controlling radionuclide contamination, anti-caking agents, acidity regulators, silage additives and denaturants.

Examples of sensory additives suitable for incorporation with the polysaccharide butyryl ester of the present invention include colorants and flavoring compounds. Coloring agent is to be interpreted broadly and may mean a substance which adds or restores color to the feed, a substance which adds color to food of animal origin when fed to an animal and/or a substance which is beneficial to the color of ornamental fish or ornamental bird.

Examples of nutritional additives suitable for combination with the polysaccharide butyryl ester of the invention include vitamins, provitamins and chemically well-defined substances with similar effects; a compound of a trace element; amino acids, salts and analogs thereof; urea and its derivatives.

Examples of animal technology additives suitable for combination with the polysaccharide butyryl ester of the present invention include digestibility enhancers, intestinal flora stabilizers and substances that favorably influence the environment. In a preferred embodiment of the invention, the at least one other feed grade material comprised in the feed is a binder, an anti-caking agent, a stabilizer, a carrier and/or a preservative. In a preferred embodiment of the invention, the at least one further feed grade material is selected from the group consisting of: yeast products, clays, fatty acid salts, silicates, sepiolite, bentonite, clinoptilolite, guar gum, xanthan gum, formic acid, sodium formate, calcium formate, acetic acid, calcium acetate, sodium propionate, calcium propionate, lactic acid, calcium lactate, tocopherol-rich extracts from vegetable oils and wheat bran. The yeast product as used herein should be interpreted broadly and may refer to yeasts and products derived therefrom, such as inactivated dry yeasts, yeast cell walls, autolysates or nucleotides obtained from e.g. Saccharomyces cerevisiae (Saccharomyces cerevisiae), Saccharomyces carlsbergensis (Saccharomyces carlsbergensis), Kluyveromyces lactis (Kluyveromyces lactis), Kluyveromyces fragilis (Kluyveromyces fragilis), Torulaspora delbrueckii (Torulaspora delbrueckii) and the like. In an embodiment of the invention, there is provided a feed material as defined above comprising at most 50 wt.%, preferably at most 40 wt.%, at most 30 wt.%, at most 25 wt.%, at most 20 wt.%, at most 18 wt.%, at most 15 wt.%, at most 10 wt.%, or at most 5 wt.% of the polysaccharide butyryl ester, based on the total weight of the composition.

In an embodiment of the invention, there is provided a feed material as defined herein comprising one or more other feed grade materials, for example a feed grade material as defined above, in an amount (combined) of at least 1 wt.%, preferably at least 2 wt.%, at least 3 wt.%, at least 5 wt.%, at least 10 wt.%, at least 20 wt.%, at least 30 wt.%, at least 40 wt.%, or at least 50 wt.%, based on the total weight of the composition.

In an embodiment of the invention, the feed grade composition is a livestock feed, also known as forage, comprising the polysaccharide butyryl ester described herein and one or more animal feed ingredients. As understood by those skilled in the art, the term "feed ingredient" as used herein refers to a feed component that provides the general nutrients required for the normal growth and development of an animal, the key nutrients being amino acids, carbohydrates, lipids, vitamins and minerals. Generally, feed ingredients are broadly divided into protein sources, energy sources, fat sources and mineral sources.

Accordingly, in an embodiment of the invention there is provided a livestock feed as defined herein, wherein the one or more feed ingredients are selected from the group consisting of: a protein source, an energy source, a fat source, and a mineral source. Suitable examples of protein sources include soybean meal, rapeseed meal, palm kernel meal, sunflower meal, peas, soybeans, lupins, fish meal, poultry meal, and plasma. Suitable examples of energy sources include corn, wheat, barley, and rice. Suitable examples of fat sources include fish oil, animal fats and oils, corn oil, soybean oil, rice bran oil, palm oil, and rapeseed oil. Suitable examples of mineral sources include calcium, magnesium, phosphorus, potassium, sodium, copper, selenium, zinc, iron, manganese, iodine, cobalt.

In an embodiment of the invention there is provided a livestock feed as defined herein, comprising at least 0.0001 wt.% of the polysaccharide butyryl ester, preferably at least 0.001 wt.%, at least 0.005 wt.%, at least 0.01 wt.%, at least 0.025 wt.%, at least 0.05 wt.%, or at least 0.1 wt.%, based on the total weight of the composition. In an embodiment of the invention there is provided a livestock feed as defined herein, comprising at most 10 wt.% of the polysaccharide butyryl ester, preferably at most 5 wt.%, at most 2 wt.%, at most 1 wt.%, at most 0.5 wt.%, or at most 0.1 wt.%, based on the total weight of the composition.

In an embodiment of the invention, the feed grade composition has a free acid content of less than 5 wt%, preferably less than 2 wt%, preferably less than 1 wt%, preferably less than 0.5 wt%, preferably less than 0.1 wt%, preferably less than 0.05 wt%, preferably less than 0.01 wt% of the composition. The free acid content can be determined by suitable methods known to those skilled in the art.

In an embodiment of the invention, the feed grade composition has a water content of less than 5 wt%, preferably less than 2 wt%, preferably less than 1 wt%, preferably less than 0.5 wt%, preferably less than 0.1 wt%, preferably less than 0.05 wt%, preferably less than 0.01 wt% of the composition. The water content can be determined by suitable methods known to the person skilled in the art, for example by Karl-Fischer titration.

The feed grade composition comprising the polysaccharide butyryl ester as described above may be provided in the form of a powder, a compressed dose, a granule or a pellet. In a preferred embodiment, the polysaccharide butyryl ester is homogeneously distributed throughout the feed grade composition.

In a preferred embodiment, the feed grade composition is provided in the form of a compressed dose, granules or pellets and the polysaccharide butyrate is distributed in the primary particles that make up the food grade composition.

In a highly preferred embodiment, the feed grade composition is provided in the form of a compressed dose, granule or pellet, wherein the primary particles that make up the food grade composition do not comprise distinguishable layers or phases. In a very preferred embodiment, the feed grade composition is provided in the form of a pressed formulation, granules or pellets, wherein the primary particles constituting the food grade composition comprising the polysaccharide butyryl ester do not comprise a coating consisting of more than 70% by weight of the total coating, more than 50% by weight of the total coating, or more than 20% by weight of the total coating, or comprising more than 70% by weight of the total coating, more than 50% by weight of the total coating, or more than 20% by weight of the total coating.

A second aspect of the invention relates to a method of treating an animal by administering the polysaccharide butyryl ester as defined herein. Generally, as will be appreciated from the foregoing, such a method comprises enterally (particularly orally) administering the polysaccharide butyryl ester to an animal, preferably in admixture with animal feed, for the purpose of affecting the physiological state of the animal, particularly improving the intestinal health, condition and/or performance of the animal. Thus, the methods of the invention may have prophylactic or therapeutic effects. The process of the invention may also have purely economic objectives.

According to the invention, the animal is preferably a livestock animal, including poultry, aquatic species and mammalian species. Examples of poultry include poultry, such as turkeys, ducks, and chickens. Examples of aquatic species include fish species (such as salmon, trout, tilapia, catfish, and carp), and crustacean species (including shrimp and prawn). Examples of mammalian species include ruminant species (e.g., sheep, goats, and cattle), as well as non-ruminant species (e.g., horses, pigs, and swine). In a preferred embodiment of the invention, the animal is selected from the group consisting of monogastric animals with a posterior intestinal fermentation. In other preferred embodiments, the animal is selected from the group consisting of: chicken, pig, horse, calf, goat, sheep, rabbit, dog, cat and fish. In a more preferred embodiment, the animal is selected from the group consisting of: chicken, pig, horse, calf, goat, sheep and rabbit, more preferably selected from the group consisting of: chicken, pig, horse and calf, more preferably selected from the group consisting of: chickens and pigs, most preferably chickens.

In an embodiment of the invention, the animal to be treated may be an animal in weaning period, an animal in development period or an animal in slaughtering period. In a preferred embodiment, the animal is an animal at a developmental stage.

In an embodiment of the invention, the method of treatment comprises feeding the animal a feed or forage, typically a feed or forage containing the polysaccharide butyryl ester as defined elsewhere herein. The optimal treatment regimen may depend on the species being treated and/or the effect desired, and it will be within the ability of those skilled in the art, based on the present teachings, to determine an appropriate treatment regimen. In an embodiment of the invention, the treatment will comprise enteral (e.g. oral) administration of the polysaccharide butyryl ester, preferably at least 0.001 wt.%, at least 0.005 wt.%, at least 0.01 wt.%, at least 0.025 wt.%, at least 0.05 wt.%, or at least 0.1 wt.%, at a dose of at least 0.0001 wt.%, based on the total weight of the animal feed consumed by the animal within 24 hours. In an embodiment of the invention, there is provided a treatment as defined herein, comprising enterally (e.g. orally) administering the polysaccharide butyryl ester, preferably at most 5 wt.%, at most 2 wt.%, at most 1 wt.%, at most 0.5 wt.%, or at most 0.1 wt.%, at a dose of at most 10 wt.%, based on the total weight of the animal feed consumed by the animal within 24 h.

In an embodiment of the invention, the polysaccharide butyryl ester is administered at a dose that: at least once weekly, preferably at least once every three days, more preferably at least once every two days, most preferably once daily.

The method of the invention may be carried out for a variety of reasons, which will be apparent on the basis of the foregoing, in particular for the purpose of improving and/or maintaining the health of the animal and/or for the purpose of improving the performance of the animal.

Accordingly, in an embodiment of the invention, there is provided a method as defined herein, wherein said method is non-therapeutic. Accordingly, there is provided a method as defined herein, wherein the animal to be treated is a healthy or normal animal. In a preferred embodiment of the invention, the method is aimed at reducing feed conversion ratio, increasing live body weight and/or increasing average daily gain.

In embodiments of the invention, the method may be intended to increase the weight of a living body by more than 1%, preferably more than 2%, preferably more than 4%, preferably more than 6% within a given time period, e.g. slaughter or day 35, preferably day 35. In a preferred embodiment, the method is intended to increase the weight of the living body by 1-12%, preferably 2-6%, in a given time. The skilled person can determine the increase in weight of the living body at a given time by routine experimentation, for example in vivo using a control group.

In an embodiment of the invention, the method may be aimed at reducing the feed conversion rate calculated over a given period of time (e.g. a supplementary feeding period or a present period, preferably a supplementary feeding period) by more than 1%, preferably by more than 2%, preferably by more than 4%, preferably by more than 6%. In a preferred embodiment, the method is intended to reduce the calculated feed conversion ratio in a given period by 1-12%, preferably 2-6%. The skilled person can determine the calculated decrease in feed conversion ratio over a given period of time by routine experimentation, for example in vivo using a control group.

In an embodiment of the invention, the method may be aimed at increasing the average daily gain calculated over a given period of time (e.g. a supplementary feeding period or a life-span, preferably a supplementary feeding period) by more than 1%, preferably by more than 2%, preferably by more than 4%, preferably by more than 6%. In a preferred embodiment, the method is intended to increase the average daily gain calculated over a given period of time by 1-12%, preferably 2-6%. The skilled person can determine the calculated increase in average daily gain over a given period of time by routine experimentation, for example in vivo using a control group.

In an embodiment of the invention, there is provided a method as defined herein, wherein the method is carried out with the aim of improving or maintaining the health of an animal.

Thus, in an embodiment of the invention, there is provided a method as defined herein, wherein the animal to be treated is an animal suffering from or at risk of suffering from a disease or pathology. Furthermore, in an embodiment of the invention, there is provided a method as defined herein for the therapeutic and/or prophylactic treatment of a disorder or pathology in an animal.

More specifically, in an embodiment of the invention, there is provided a method as defined herein, wherein the animal to be treated is an animal suffering from or at risk of a pathogen infection, preferably an intestinal pathogen infection, more preferably a caecum and/or colon pathogen infection. In an embodiment of the invention, there is provided a method as defined herein for the treatment and/or prevention of a pathogen infection, preferably an intestinal pathogen infection, more preferably a caecum and/or colon pathogen infection. According to the invention, the pathogen may be selected from bacteria, eimeria, viruses and fungi, more preferably the pathogen is selected from bacteria, most preferably from Clostridium acetobutylicum (Clostridium acetobutylicum), Escherichia coli (Escherichia coli), Streptococcus cremoris (Streptococcus cremoris), Lactococcus lactis (Lactococcus lactis), Lactococcus cremoris (Lactococcus cremoris), Clostridium perfringens (Clostridium perfringens), Campylobacter jejuni (Campylobacter jejuni), Campylobacter coli (Campylobacter coli), lawsonia intracellularis (lawsonialcellalutella), Brachyspira hyodysenteriae (brachiococcus caecum), Streptococcus suis (Streptococcus suis), salmonella typhi (salmonella capsulatus) and combinations thereof, preferably Clostridium proconvulus, Clostridium proconceptis, Clostridium proconcepti, and combinations thereof.

In one embodiment, a method as defined herein is provided, wherein the animal to be treated is an animal suffering from or at risk of suffering from a gut flora dysbiosis, in particular a caecum and/or colon dysbiosis. In an embodiment of the present invention, there is provided a method as defined herein for improving the intestinal microbiota and/or maintaining a healthy intestinal microbiota of an animal, in particular improving the caecum and/or colon microbiota and/or maintaining a healthy caecum and/or colon microbiota. In an embodiment of the invention, there is provided a method as defined herein which results in and/or aims at increasing the number of microorganisms from bacteria of the genus lactobacillus or bifidobacterium in the gastrointestinal tract, preferably the lower gastrointestinal tract, preferably the cecum or colon. In an embodiment of the invention, there is provided a method as defined herein, which results in and/or aims at increasing the ratio of the number of microorganisms from bacteria of the genus lactobacillus or bifidobacterium compared to the number of microorganisms from bacteria of the family enterobacteriaceae in the gastrointestinal tract, preferably the lower gastrointestinal tract, preferably the cecum or colon. In an embodiment of the present invention, there is provided a method as defined herein, which results in and/or aims at increasing the ratio of the number of microorganisms from bacteria of the genus lactobacillus or bifidobacterium compared to the number of microorganisms from bacteria of the genus salmonella in the gastrointestinal tract, preferably the lower gastrointestinal tract, preferably the cecum or colon. In an embodiment of the invention, there is provided a method as defined herein that results in and/or aims at improving the intestinal microbial flora, including increasing the ratio of the number of microorganisms from bacteria of the genus lactobacillus or bifidobacterium compared to the number of microorganisms from bacteria of the genus salmonella in the gastrointestinal tract, preferably the lower gastrointestinal tract, preferably the cecum or colon, wherein said ratio is approximated by determining the number of microorganisms representing one bacterium of each genus and calculating the ratio using the numbers of microorganisms representing the bacteria. According to such embodiments, decreasing or increasing the number of microorganisms or the ratio of the number of microorganisms should be interpreted broadly and may for example be understood to mean one or more of the following:

The decrease or increase in the number of Colony Forming Units (CFU) is determined 1-10 days, preferably 1-5 days, preferably 3 days, after the start of the treatment, by suitable methods known to the person skilled in the art, and compared with a group of untreated animals.

A decrease or increase in the number of Colony Forming Units (CFU) measured in the same animal before treatment and 1 to 10 days, preferably 1 to 5 days, preferably 3 days after the start of treatment, determined using suitable methods known to the person skilled in the art, or

Any other method known to the person skilled in the art for determining the effect of the polysaccharide butyryl ester used according to the invention on the feed supplement.

Another aspect of the present invention relates to the use of the polysaccharide butyryl ester as defined herein and/or a feed grade composition containing said polysaccharide butyryl ester as defined herein in the method of treatment as defined above.

Another aspect of the present invention relates to the use of a polysaccharide butyryl ester as defined herein and/or a feed grade composition containing said polysaccharide butyryl ester as defined herein, in the preparation of a composition for use in a method of treatment as defined herein above.

Another aspect of the present invention relates to a polysaccharide butyryl ester as defined herein and/or a feed-grade composition comprising said polysaccharide butyryl ester as defined herein, for use in a method of treatment as defined herein above.

Another aspect of the invention relates to the use of the polysaccharide butyryl ester as defined herein as an animal feed component or ingredient.

Another aspect of the invention relates to a method of preparing an animal feed composition as described herein, the method comprising:

providing a first animal feed component,

providing a polysaccharide butyryl ester, and

mixing the first animal feed component with the polysaccharide butyryl ester to a homogeneous mixture.

In one embodiment, the method comprises:

providing a first animal feed component,

providing the polysaccharide with a butyryl ester,

mixing the first animal feed component with the polysaccharide butyryl ester to a homogeneous mixture, and granulating the homogeneous mixture.

Accordingly, the present invention has been described with reference to certain embodiments discussed above. It will be appreciated that these embodiments are susceptible to various modifications and alternative forms, which are well known to those skilled in the art. Many modifications may be made to the structures and techniques described herein, in addition to those described above, without departing from the spirit and scope of the present invention. Thus, while specific embodiments have been described, these are merely examples and do not limit the scope of the invention. Furthermore, for a proper understanding of the present document and the claims hereof, it should be understood that the verb "to comprise" and its conjugations is used in its non-limiting sense to mean that items following the word are included, but items not specifically mentioned are not excluded. In addition, reference to an element by the indefinite article "a" or "an" does not exclude the possibility that more than one of the element is present, unless the context clearly requires that only one of the elements be present. Thus, the indefinite article "a" or "an" usually means "at least one". The following examples are for illustrative purposes only and are not intended to limit the scope of the present invention in any way.