The present invention relates to a micro encapsulated additive provided with an editable external coating, as well as to the use thereof.

FIELD OF THE INVENTION

In the last decades many documents have been published on rumen stable and rumen protected feed additives. Ruminant animals have evolved a large pre-gastric fermentation process that enables digestion of feedstuffs normally indigestible by mammalian hydrolytic-enzymatic processes.

Micro encapsulated additives are known from European patent application number EP 0 234 921. European patent application number EP 0 234 921 discloses a silage additive, for addition to animal feedstuff material in order to produce a preservative effect by ensilage, comprising a stable composition containing molasses and vinegar, wherein at least one bacterial inoculant, such as Streptococcus faecium and Lactobacillus plantarum, is included in the composition, in which the bacterial inoculant is in a micro-encapsulated form.

European patent application number EP 3 703 507 relates to a process of encapsulating or coating an animal feed ingredient, e.g. an amino acid, the method comprising: mixing an emulsifier with a coating agent, thereby forming a coating mixture; and placing the coating mixture over an animal feed ingredient particle, thus encapsulating or coating the animal feed ingredient, wherein the emulsifier is selected from the group lecithin, monoglyceride, sorbitan ester, polyglycerols, and combinations thereof, and wherein the coating agent is selected from the group consisting of an oil and a fatty acid, and combinations thereof. The pastillated granule is in a shape approximating a half-sphere having an aspect ratio (diameter/height) of 1.5 to 2.5 and has a size of 2.2-5.0 mm or 2.2-3.5 mm. The amino acid has a particle size of 50-120 mesh or 80-110 mesh and is present in the pastillated granule at 25- 85% by weight, 25-75% by weight, or 35-75% by weight.

International application WO 2016/154574 discloses a rumen by-pass composition, comprising a first rumen by-pass component and a nutritional composition, wherein the first rumen by-pass component comprises a fatty acid composition, i.e. a palmitic acid compound, wherein the nutritional composition is configured to substantially bypass rumen when administered to a ruminant. The rumen by-pass composition is formed as solid particles and at least partially encapsulates the nutritional composition.

US 2019/200664 relates to a method for making thermally stable particulate micronutrient formulations, comprising providing particles of an iron supplement mixed with an antioxidant polymer such as hyaluronic acid and/or one or more fat soluble vitamin, dispersing the iron mixture or vitamin in a pH-sensitive enteric polymer, forming particles by spray drying or spin disking, and wherein the particles are sprayed into starch or other non-agglomerating polymeric powder to form a powder coating when the particles contain fat soluble vitamins. Formulations are made up of one or more micronutrients distributed in a first matrix which is coated or encapsulated by a second matrix formed by one or more pH-sensitive, thermally stable materials.

W02009026115 relates to a method for acidifying the diet of a mammal without negatively impacting the palatability of the diet, the method comprising combining the mammal's feed ration with a microgranule comprising a core material consisting essentially of at least two anionic salts; and a shell wall that encapsulates the core material, wherein one of the anionic salts is a chloride and one of the anionic salts is a sulfate, wherein the anionic salts are selected from the group consisting of ammonium chloride, ammonium sulfate, calcium chloride, calcium sulfate, magnesium sulfate, and magnesium chloride. The shell wall is a material selected from the group consisting of a biopolymer, a semi-synthetic polymer, edible wax, and a mixture thereof, wherein the microgranule has an average diameter ranging from about 1 micron to about 1500 microns and the microgranule comprises from about 40% to about 60% by weight of anionic salts and from about 40% to about 60% by weight of the shell wall.

US 2006/073193 relates to the use of a granule comprising a core comprising an active compound and a coating comprising a salt for steam treated pelletized feed compositions, wherein the granule comprises at least 75% of active compound with retained activity after steam pelleting, the granule comprises one or more of the following: the particle size of the granule is below 400 micrometre, the thickness of the salt coating is at least 8 micrometre, the active compound is thermo labile, the granule further comprise a wax coating, the granule further comprise a lactic acid source, and the active compound in the core of the granule is an enzyme.

With modern encapsulation methods it is possible to produce hot melt coatings that will give good water stability of the additive. However, an issue with these hot melt coatings (HMC) is that they are indigestible since they have a very poor digestibility of about 9 % about 40% and as a result of volume contraction will form coating defects during storage and low temperature exposure.

An object of the present invention is to provide feed additives that are not easily metabolized by micro-organisms in the rumen in such a way that during the retention time in the rumen of about 2-14h the additive is not fermented and arrives in the abomasum intact.

Another object of the present invention is to provide micro encapsulated additives that are stable during production and storage.

Another object of the present invention is to provide micro encapsulated additives wherein the amount of coating digested is suitable for releasing the components of the encapsulated core in abomasum and / or small intestine.

An object of the present invention is thus to provide feed additives which are rumen bypass and become bio-available in the intestine and that can be stored and applied under cold conditions without loss of coating integrity.

STATEMENTS OF THE INVENTION

The present invention thus provides in a first aspect a micro encapsulated additive provided with an editable external coating, wherein the editable external coating is a hot-melt coating, the additive having a particle size of more than 50 micron and less than 500 micron and the coating having a layer thickness of more than 5 micron and less than 50 microns.

In an example the particle size is at least 100 micron, preferably at least 150 micron and at most 400 micron, preferably at most 350 micron.

In an example the layer thickness of the coating is at least 10 micron, preferably at least 15 micron and at most 40 micron, preferably at most 30 micron.

The present inventor found that micro encapsulated additives with an editable external hot-melt coating can only be water (rumen) stable (e.g. hours submersed in an aqueous solution) and at the same time be digestible in the intestine, when the particle size is within a specific range of more than 50 micron and less than 500 micron and when the coating has a layer thickness of more than 5 micron and less than 50 micron. At these particle sizes and coating thickness the addition of auxiliaries like emulsifier (e.g. glycerol monostearate), plasticizers and calcium carbonate in the coating layer can further enhance the digestibility of the micro encapsulated additive. The present inventor found that a hot-melt coating has a poor digestibility because they are too thick. The ruminant has a very low capacity to digest the coating layer. When the layer is too thick, only a small amount will be digested, which is not enough to liberate the active ingredient in the core before it leaves the small intestine. Thus, by providing a specific ratio between the size of the core, i.e. the additive(s), and the hot-melt coating a rumen stable and intestinal digestible micro encapsulated additive is obtained.

The present inventor found that when using such micro encapsulated additives the digestion will be optimal (large surface for enzymatic digestion, no emulsification required). In addition, the present inventor also found that when using such micro encapsulated additives the amount of coating digested will be enough to release the core, i.e. the enzymes only have to digest the coating that will give the steep increase of water (rumen) stability. ). Moreover, the present inventor also found that when using such micro encapsulated additives a stable production and storage is guaranteed wherein no coating defects are encountered that may destroy the coating and the release properties of the hot-melt coating, and volume contraction will not cause coating defects under normal storage conditions. The digestion of the coating may start at the low pH in the abomasum, e.g. by adding calcium carbonate to the hot- melt coating, and during its passage through the small intestine which will enable the ruminant to absorb the additive, also identified as digestibility or bio-availability.

In an example the coating comprises several layers, wherein the sum of the thickness of the individual layers is more than 5 micron and less than 50 micron.

During the coating process a coating agent is applied on the surface of the core and therefor the percentage of coating in the coated particle will increase. At the same time the water (rumen) stability will increase. The relationship between the number of coating layers and the water stability is shown in the enclosed Figure 1. As can be seen figure 1 resembles a pH graphic. The coating process will be stopped when the addition of more coating only gives a moderate increase in rumen (water) stability. From Figure 1 one will notice that a high increase in water stability will end after the deposition of four layers of coating. In such a situation the cow only has to digest the coating that gave the steep increase of water stability.

An example of a shape of the core is a sphere. The shape of a sphere will provide the thinnest coating. Other shapes will have higher surface/volume ratio and therefor need more coating. Sharp edges, thin plates etc. will be more difficult to coat and therefor need a thicker coating. Core materials that are hygroscopic, e.g. ammonium chloride, calcium chloride, need a thicker layer to reduce the water vapour permeability (WVP) or need coating materials that have a lower WVP, such as beeswax.

It is known that tension in the coating will occur and increase during solidification/crystallization and storage. Since hot-melt coatings are polymorphic they are prone to volume contraction. Hot-melt coatings have also a reduced plasticity and therefor prone to coating defects. This coating tension that is the cause of the above mentioned defects, can be reduced by lowering the hot-melt coating span. By reducing the absolute surface of the core, the present inventor reduced the absolute tension in the hot-melt coating. When using a core with a particle size of <500 micron the present inventor has achieved a stable hot-melt coating for storage under normal storage conditions. For stability at extreme sub-zero temperatures (e.g. -20°C) the particle size must be in the range of <200 micron.

In another example the percentage coating (vol.%) in the micro encapsulated additive ranges between 5 vol.% and 80 vol.%. for an additive having a particle size of more than 50 micron and less than 500 micron.

The retention time in the rumen is mainly influenced by the particle size and weight of the feed material. The rumen has a pylorus of about 2 mm. Water and in water dissolved feed materials have a retention time of about 2 h, while long structural carbohydrates can have a retention time up to12 h. The present inventor found that using a core of <500 micron and a coating percentage of about 33% provided a good rumen stability.

The present inventor found that coating defects will occur as a result of volume contraction after solidification and surface roughness. Large particles have higher mounts and deeper valleys than smaller particles. This altitude variation will cause more coating defects because the coating will contract towards the peak and valley and that will cause the coating to crack on the slope. Although smaller core particles have more surface and therefor need a higher hot-melt coating percentage (%) because of the higher surface/volume ratio, the coating diameter is absolute thinner (microns) than of a larger core with a larger span, with a lower hot-melt coating percentage. This aspect has been shown in Figure 2.

In an example the additive is at least one compound chosen from the group of B vitamins, vitamins A, vitamins C, vitamins K, vitamins D, vitamins E, group of amino acids, cysteine, histidine, alanine, glycine, arginine, threonine, valine, leucine, isoleucine, phenylalanine, glutamine, glutamic acid methionine, lysine, tryptophan, antibiotics, group of products with antibiotic properties, monolaurin or glycerol monolaurate, mid chain fatty acids, caproic acids, caprylic acid, capric acid, lauric acid, (poly)unsaturated fatty acids, choline chloride, silicium dioxide , a group of glucogenic precursors, dextrose, sucrose, oligosaccharides, disaccharides, denaturated starch, molasse, maltodextrin, mono propylene glycol, glycerol, vegetable protein, group with anionic properties, calcium chloride, ammonium chloride, hydrochloric acid, magnesium chloride, insect protein, talc, (poly)unsaturated fatty acids, rapeseed oil, emulsifiers, ethoxylated sorbitan esters, polysorbate, glycerol monostearate, lecithin, urea, poly ethylene glycol (PEG), micro-organisms, lactobacillus, lactobacillus bifidus, yeasts, such as brewer’s yeast, markers, such as arabinose, xylose, or a combination of one or more thereof. In an example the additive may comprise one or more additives.

In an example the hot-melt coating is at least one compound chosen from the group of hydrogenated palm oil, including fractionated hydrogenated palm oil, hydrogenated soybean oil, hydrogenated corn oil, hydrogenated vegetable oils, hydrogenated coconut oil, waxes, beeswax, carnauba wax, candelita wax, poly ethylene glycol, calcium carbonate, mono- and di glycerides, glycol monolaurate, glycerol monostearate, emulsifiers, ethoxylated sorbitan esters, polysorbate, surface tension reducers, hydrogenated coconut oil, calcium salts of fatty acids, lecithin, hydrogenated rapeseed oil, hydrogenated cottonseed oil, hydrogenated sunflower oil, hydrogenated fatty acids, stearic acid, palmitic acid, unsaturated triglycerides and fatty acids, gelatin and lauric acid, or a combination of one or more thereof. In an example the editable external coating may comprise one or more hot-melt coatings.

In an example the core material may also comprise one or more components listed above as hot-melt coating. This will result in a composite core material, i.e. one or more additives mixed with one or more hot-melt coatings. The composite core is surrounded by the editable external coating. In an example the editable external coating may comprise one or more hot-melt coatings.

In an example the micro encapsulated additive provided with an editable external coating the additive is methionine and the coating comprises hydrogenated palm oil. In an example the micro encapsulated additive provided with an editable external coating the additive is lysine and the coating comprises hydrogenated palm oil.

In an example the micro encapsulated additive provided with an editable external coating the additive is choline chloride and the coating comprises hydrogenated palm oil.

In an example the micro encapsulated additive provided with an editable external coating the additive is dextrose and the coating comprises hydrogenated palm oil.

In an example the micro encapsulated additive provided with an editable external coating the additive is propylene glycol and the coating comprises hydrogenated palm oil.

In an example the micro encapsulated additive provided with an editable external coating the additive is glycerol monolaurate and the coating comprises hydrogenated palm oil.

In an example the micro encapsulated additive provided with an editable external coating the additive is ammonium chloride and the coating comprises hydrogenated palm oil.

The present inventor found that the hot-melt coating must be stable under high (40°C) and low temperature (-20°C). In addition, the hot-melt coating must be stable under high humidity for long period of time. The final micro encapsulated additive will be mixed with other ingredients which may contain (crystal) water and stored in bags. The additive must be stable in liquid water solutions for about 2-14 h (rumen). The hot-melt coating must be stable during mixing with other feed ingredients and the coating must be digestible otherwise the additive is not released. In this report we mean with an HMC, a physical external coating.

In the present description the term “micro encapsulated additive” includes an embodiment wherein the active ingredient or additive is to be seen as core surrounded by the hot-melt coating. The coating technique for manufacturing the micro encapsulated additive is for example fluidized bed dryer with Wurster process. According to the Wurster technology a spray nozzle is located at the bottom of the fluidized bed. The particles are moved with a fluidizing air stream that is designed to induce a cyclic upward flow of particles, past the spray nozzle. The nozzle sprays atomized droplets of coating solution or suspension concurrently with the particle flow, depositing droplets on the surfaces of the particle as they pass upward into an expansion chamber. The Wurster fluid bed process is used to apply a hot melt coating. Wax is heated to a molten state and sprayed in the same manner as a solution suspension. Process parameters are adjusted to congeal molten wax droplets on the surfaces of the circulating particles. The classical pan coater technique consisting of a drum coater with an automatic spraying system can also be used for manufacturing the micro encapsulated additives.

In an example of a method for the preparation of the micro encapsulated additive provided with an editable external coating a carrier for the additive is used, especially when the additive is a liquid component. In a first step the carrier, for example silicium dioxide, is brought into contact with the liquid component and the liquid component is absorbed by the porous carrier material. In a second step the carrier material including the additive is coated with the coating material.

In another example of a method for the preparation of the micro encapsulated additive provided with an editable external coating the core material may comprise a combination of materials, for example a component that is solid at room temperature but liquid when heated. Such a component is heated above its melting temperature and then the liquid component is mixed with the additive, i.e. the active material. After mixing the composition thus obtained the composite is spray cooled and solid granules are obtained. These granules are subsequently provided with the coating material.

The present invention also relates to the use of a micro encapsulated additive provided with an editable external coating as discussed above for preparing a feed composition for ruminants.

The present invention also relates to a feed composition for ruminants comprising a micro encapsulated additive provided with an editable external coating as discussed above.

The present invention also relates to the use of a micro encapsulated additive provided with an editable external coating as discussed wherein during a retention time in the rumen of about 2-14h the additive is not fermented and arrives in the abomasum intact for releasing the components of the encapsulated core in abomasum and / or small intestine.

Example As core material ammonium chloride (manufacture Dallas Group of America) having a core diameter of 323 micron was coated with a vegetable-based triglyceride, i.e. hydrogenated palm oil. The diameter of the micro encapsulated additive provided with an editable external coating was 400 micron.

A simple test was conducted to demonstrate the digestibility of the fat coating in the field. Ammonium chloride (NhUCI) was used as an active matter in this test. This raw material is often used in feed as an anionic salt to acidify the blood (and therefore the urine). The ammonium chloride was coated with the fat coating (as described above) and has a rumen stability of 65% at 18 hours. When the pH drops till the target level (which is calculated with the standard DCAD formula) it is certain that the (ammonium) chloride is fully bio-available. DCAD stands for dietary cation- anion difference. It is a simple calculation of adding together the milliequivalents of dietary cations (sodium + potassium) and subtracting the sum of the milliequivalents of dietary anions (chloride + sulfur).

Three experiments were set up with different rations and DCAD values. On the first test day the urinary pH was measured. During the experiments the urinary pH was randomly tested to monitor pH changes. In the early morning of day 4 (trial 2 and 3) and on day 5 (trial 1) the final urinary pH was measured. Used procedure: for every measurement 100 till 300 ml urine was collected for pH measurement (HANNA HI 98127). The accuracy was 0,1 (supplement 1).

Trial 1 (far-off) consisted of a test group (4 multiparous cows, 3 heifers) and a Control group (5 multiparous cows, 2 heifers), Trial 2 (far-off) consisted of a test group (3 multiparous cows, 5 heifers) and a Control group (3 multiparous cows, 5 heifers) and Trial 3 (close-up) consisted of only 5 multiparous cows.

Table 1: Ration composition in % DM

* Coated ammonium chloride with 32% coating and 65% rumen stability

In trial 1 and 2 the same basic ration was used. The only difference is the feeding rate of the coated ammonium chloride. In trial 3 a close-up ration was used with several other feed stuffs in it.

Every day the cows received a TMR. The ration of the test group was spread out (supplement 1). The coated NhUCI was divided over the feed and mixed in with a fork. The procedure was the same every day and performed by the same person to obtain a homogeneous result. To exclude blending and cross feeding a partition was made between the different groups. Every morning and evening the feed was pushed back into the feed bunker. In trial 3 the same procedure was followed except for the absence of a control ration. Around 10 am the head gate was closed, and the feed refusals removed. Thereafter fresh feed was supplied.

The DM intake of trial 1 , 2, and 3 was ±13.5 kg, ±13.0 kg and ±14 kg. This means that the cows consumed respectively 210, 315 and 350 grams coated NH4CI/cow/day. At the beginning and at the end of the experiments the urinary pH was measured. These values are shown in table 2. Table 2: Urinary pH

When the DCAD value is -3 the urinary pH can be expected to drop until ± 7.0. When the DCAD value is -14 the pH should drop till 5.4. The pH of trial 2 and 3 was respectively 5.3 and 5.5 and approached the value of 5.4.

If the coating is not available in the intestine, the chlorides would not be released because the coating didn’t break down. The estimated effect on urinary pH is shown in table 3.

Table 3: Estimated results of trial 3 when fat coating is (in) digestible in the intestine.

In this experiment the urinary pH dropped to 5.5. The calculated urinary pH, at a 100% release rate would drop to 5.4. The calculated pH at a 0% release rate is 7.8. Therefore, it can be concluded that the coating released 100% of the active ingredient (ammoniochloride) in the intestine.