NL2020001B1

NL2020001B1 - Coated choline chloride granules

Info

Publication number: NL2020001B1
Application number: NL2020001A
Authority: NL
Inventors: Ketels Eddy; Segers Ludo
Original assignee: Orffa Additives B V
Priority date: 2017-12-01
Filing date: 2017-12-01
Publication date: 2019-06-11

Abstract

The current invention concerns a method for producing coated choline chloride granules for use as a feed supplement, said method comprising the steps of — providing feed-grade choline chloride, said choline chloride being provided as a powder having an average particle size of 80-150 um, — mixing said choline chloride with one or more binders, thereby obtaining a mixture; — granulating the dried mixture, thereby obtaining granules; — drying said granules; and — coating said granules with one or more fats, thereby obtaining fat coated choline chloride granules; wherein said granules are dried at a temperature of between 70°C and 100°C to a moisture content of less than 1 wt%. In a second aspect, the current invention pertains to a feed supplement comprising fat-coated choline chloride granules obtainable by a method according to the present invention.

Description

COATED CHOLINE CHLORIDE GRANULES TECHNICAL FIELD

The invention pertains to the technical field of coated granular feed additives, in particular to fat-coated granules comprising choline chloride.

BACKGROUND

It has become common practice to supplement the diet of animals with certain feed additives, the use of which may either generally improve the health conditions of the animals, or increase feed efficiencies in meat producing animals, or increase milk productivity and/or milk quality in milk producing animals.

Among these additives, special attention has been recently dedicated to choline, with particular reference to the breeding of ruminants.

Choline (2-hydroxyethyl(trimethyl)azanium) is an essential nutrient for normal animal growth and performance. Choline is an essential component for cell walls, nerve transmission (it is a precursor of acetyl-choline), fat metabolism and transport. Choline is also an important donor of methyl groups in various metabolic processes.

Supplemental choline seems to have an effect on feed efficiencies, and promotes the mobilized lipids from adipose tissues through the liver and the mammary gland, thereby improving the energy balance and preventing ketosis in farm animals, and more in particular, in ruminants.

Accordingly, it is important to pass the biologically active substances through the rumen without decomposition by microorganisms to allow the biologically active substances to be effectively digested and absorbed in the abomasum and subsequent digestive tract.

Thus, a so-called rumen-bypass granular agent, i.e., an agent which is not solubilized or decomposed in the rumen and is dissolved and absorbed in the abomasum and downstream thereof, is important to an effective utilization of physiologically active substances in ruminants, and various such granular agents have been developed.

Moreover, it has been found that moisture reduces the rumen-stability and activity of such agents. It is therefore desired to provide an efficient method allowing production of granular choline chloride which comprises a minimal moisture content, and which shows sufficient rumen-bypass characteristics.

The invention aims to provide a solution for at least some of the problems mentioned above. More in particular, the invention aims to provide a method for producing rumen-bypass granular choline chloride agents which comprise a limited moisture content, and a feed additive comprising rumen-bypass granular choline chloride agents with a limited moisture content.

SUMMARY OF THE INVENTION

The present invention describes in a first aspect a method for producing coated choline chloride granules according to claim 1.

Such method has the advantage that a coated choline chloride granule with minimal moisture content can be produced cost-efficiently, simply, and reliably. More in particular, a method according to the present invention allows production of coated choline chloride granules having excellent rumen-bypass characteristics, an optimal bioavailability and an unprecedented bioactivity.

In a second aspect, the invention relates to a granule for use as feed supplement according to claim 9.

These granules comprise a minimal moisture content, have great rumen-bypass and stability characteristics, and show an optimal bioavailability and bioactivity.

DESCRIPTION OF FIGURES

Figure 1 is a chart showing the influence of moisture content on the activity of coated choline chloride according to an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The invention pertains to a method for producing fat coated choline chloride granules.

Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the present invention.

As used herein, the following terms have the following meanings: "A", "an", and "the" as used herein refers to both singular and plural referents unless the context clearly dictates otherwise. By way of example, "a compartment" refers to one or more than one compartment. "About" and "approximately" as used herein referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of +/-20% or less, preferably +/-10% or less, more preferably +/-5% or less, even more preferably +/-1% or less, and still more preferably +/-0.1% or less of and from the specified value, in so far such variations are appropriate to perform in the disclosed invention. However, it is to be understood that the value to which the modifier "about" and "approximately" refer is itself also specifically disclosed. "Comprise," "comprising,", "comprises" and "comprised of" as used herein are synonymous with "include", "including", "includes" or "contain", "containing", "contains" and are inclusive or open-ended terms that specifies the presence of what follows e.g. component and do not exclude or preclude the presence of additional, non-recited components, features, element, members, steps, known in the art or disclosed therein.

The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within that range, as well as the recited endpoints.

The expression "wt%" and "% by weight" (weight percent), here and throughout the description unless otherwise defined, refers to the relative weight of the respective component based on the overall weight of the formulation.

As used herein, the term 'ruminant' means an even-toed hoofed animal which has a complex of 3- or 4-chambered stomach and which is characterized by chewing again what it has already swallowed (e.g.: cattle, bison, sheep, goats and the like).

The term 'feed-grade' means compliant with regulations for good manufacturing practices (GMPs) for animal feed.

In a first aspect, the invention provides a method for producing coated choline chloride granules for use as a feed supplement. A method according to the present invention comprises the steps of - providing feed-grade choline chloride, said choline chloride being provided as a powder having an average particle size of 80-150 pm; - mixing said choline chloride with one or more binders, thereby obtaining a mixture; - drying said mixture to a moisture content of 0-1 wt%; - dry-granulating the dried mixture, thereby obtaining granules; and - coating said granules with one or more fats.

The term 'moisture content' as used herein may include water, humectants, and/or other liquid compounds or compositions of compounds. The moisture content in a product or composition can, for example, be determined by drying a product or composition for at least 12 hours at approximately 40°C, wherein the ratio of the pre-drying mass diminished with the post-drying mass over the postdrying mass represents the moisture content of said product or composition.

Choline may be provided as one or more derivatives selected from the group comprising choline chloride, choline phosphate, choline bitartrate, choline gluconate, choline dihydrogen citrate, choline fumarate, choline carbonate, choline pyrophosphate, and any combination thereof. The preferable derivatives are choline chloride and choline pyrophosphate.

The powder particle size of the choline chloride should be such that the average particle size lies between 80 pm and 150 pm, preferably between 90 and 140 pm, even more preferably between 95 pm and 130 pm, and most preferably approximately 110 pm. The maximum particle size is preferably 250 pm or less, preferably 200 pm or less, and most preferably less than 150 pm. When the particle size becomes smaller, the durability of the granular composition tends to be improved. However, a larger particle size allows for the production of larger, less porous granules. In particular, the hydrophobic binder should be relatively uniformly compatible with the choline chloride, and potentially with the one or more excipients. When the average particle size of the choline chloride is large, the uniformity sufficient to obtain the desired properties is difficult to be attained. Furthermore, when coarse particles are present, the system tends to become non-uniform and therefore, the maximum particle size of choline chloride should be limited.

The particle size can be measured with classical sieve analysis. The high end value is an absolute value (i.e. all particles can pass through a sieve to give particles of e.g. less than about 2 mm). The lower end value is given as the size where more than 99 wt% is larger than the value stated as the lower end value. Attrition may cause some amount of smaller particles to become present, for example during transportation.

It was found that a mixture with a particle size distribution as defined by the present invention shows an optimal flowability and allows the formation of a uniform mixture, thereby optimizing the granulation process of said mixture.

In an embodiment of the present invention, the choline chloride is first grinded in an appropriate grinder (e.g. a jet grinder, a ball mill, a high speed rotational grinder) to obtain the powder particles having the above-specified particle size. However, since choline chloride is remarkably hydroscopic and becomes liquid easily, the grinding operation and the subsequent granulation operation is preferably carried out under conditions such that the choline chloride is prevented from becoming liquid. The inventors have found that such operations are to be effected preferably when the relative humidity is 10% or less, preferably 5% or less, more preferably 3% or less, such as less than 2%, or less than 1%. This can be carried out by grinding the choline chloride under a high temperature heating condition, preferably, while introducing air or under a sealed condition. Any conventional grinder such as a jet grinder, a ball mill, a high speed rotational grinder can be used as long as the above-mentioned operation conditions and the particle size limitations can be realized.

The choline chloride powder is mixed with one or more binders, thereby obtaining a mixture.

As used herein, the term 'binder' is synonymous with 'adjuvans', and means an inert substance which functions as a glue during the granulation process, thereby improving the formation of granules during the granulation process. A binder according to the meaning within the present invention should preferably be hydrophobic, and preferably has a melting point of minimum 100°C. In particular, the one or more binders are selected from the group comprising talc, cellulose derivatives (such as carboxymethylcellulose, methylcellulose and ethylcellulose), gelatin, polyvinylpyrrolidone, agar-agar, lactose, and any mixture thereof.

The binder functions as a matrix to glue the choline chloride particles together in order to obtain a strong granule when granulating the mixture. Mixing the choline chloride powder with a binder also has the advantages that the concentration of choline chloride can be modified, and that the coated granules can be provided in larger sizes thereby simplifying the dosing of choline chloride, for example when using the coated choline chloride granules as a feed supplement.

Although there are no critical limitations to the amount of choline chloride that is mixed with the one or more binders, choline chloride is preferably mixed with one or more binders in a ratio of between 10:90 and 90:10, more preferably between 20:80 and 80:20, even more preferably between 30:70 and 70:30, even more preferably between 40:60 and 60:40, and most preferably approximately 50:50.

In a more preferred embodiment, the mixture comprises a binder content of between 10 wt% and 30 wt% as compared to the total weight of the mixture.

The preferred upper limit mainly depends on the granulation and coating conditions for obtaining the desired granular composition and the preferred lower limit depends on practical and economical aspects. Basically, the durability of the granules increases with the increase in the amount of the binder within the limited range and it is recommended to use a larger amount of the binder when the particle size of the choline chloride is small.

Potentially, one or more excipients, fillers or other active material may be added to the mixture comprising choline chloride and one or more binders. Examples of further materials may include: aromatic compounds to exert a more attractive odor, emulgating compounds and/or polymers to increase viscosity and/or hardness of the coating, such as for example acrylates, polyvinylpyrrolidone polymers and the like; antioxidants; coloring agents and the like.

Desirably, the excipients usable in the present invention are those which are not or only slightly soluble under a neutral condition, but soluble in an acidic condition and acceptable to the living body. Such excipients include, for example, magnesium oxide or a mixture of magnesium oxide and at least one component selected from the group consisting of talc, calcium carbonate, magnesium carbonate, dibasic calcium phosphate (CaHP04), calcium phosphate [Ca3(P04)2], calcium oxide, calcium hydroxide, and calcium sulfate.

The particle size of the excipients should be such that an average particle size is 10 pm or less, preferably 1 to 7 pm, and the maximum particle size is 20 pm or less, preferably 10 pm or less. When the particle size becomes smaller, the durability of the granular composition tends to be improved.

Although there are no critical limitations to the amount of excipient in the composition, the preferred amount is 10% to 50%, more preferably 25% to 40% by weight in the granules before coating, and 7% to 42%, more preferably 18% to 35% by weight as compared to the total weight of the mixture. The preferred upper limit depends on practical and economical aspects and the preferred lower limit depends on the accomplishment of the desired effects.

In particular, said excipients may be selected from the non-limiting group comprising fillers (lactose, cellulose powder, calcium diphosphate, microcrystalline cellulose, sugar alcohols, e.g. mannitol, sorbitol and starch), disintegrants (starch (derivatives), croscarmellose, crosslinked PVP, carboxymethyl cellulose), lubricants (stearic acid, magnesium stearate), glidants (silicon dioxide (aerosil)), colorants, flavoring agents, or any mixture thereof.

The mixture may optionally contain, in addition to the above-mentioned constituents, any ingredients conventionally used in the animal feed, especially for a ruminant, as long as the desired properties are not adversely affected, preferably in an amount of less than 10% by weight in the mixture. Examples of such ingredients are Fe203, Fe2(C03)3, CoO, CuO, MnC03, ZnC03, and ZnO.

Prior to granulation, the mixture may be dried. Preferably, the mixture is dried at a temperature of between 60°C and 110°C, preferably between 65°C and 105°C, and most preferably between 70°C and 100°C.

In another or further embodiment, a method according to the invention comprises sieving the mixture prior to granulating. This sieving step increases the uniformity of the mixture, which in turn results in an increased efficacy and efficiency of the granulation process of said mixture, and additionally, the sieving step allows the removal of particles that are too big.

In particular, the mixture is sieved by means of a sieve having a mesh size of maximally 10 such that the obtained mixture after sieving has an average particle size of maximally 2 mm, and preferably at least 0.1 mm.

Due to the hygroscopic characteristics of the choline chloride, it is not desired to wet-granulate the mixture. Therefore, the dried mixture is preferably dry-granulated to obtain granules which are preferably essentially spherical in shape. These granules will become the core of the final coated choline chloride granules.

The granulation of the mixture is carried out in an atmosphere having a relative humidity of 10% or less, preferably 5% or less, more preferably 4% or less, such as less than 3%, less than 2% or less than 1%.

The binder content is preferably within the range from 10% to 30% by weight in the granules before coating, as mentioned above. Generally speaking, in the case of most starting materials, when the amount of binder is lower than 10 wt%, the granulation becomes difficult, whereas when the amount of the binder is larger than 30 wt%, the particles become larger, i.e., coarse powder particles are sometimes formed, and the desired granulation becomes difficult. Hence, the binder ratio should be controlled, depending upon the kinds and the particle sizes of the choline chloride, and potentially the particle sizes of the excipients.

The granulating step may comprise any method of granulation known to a skilled person in the art, such as roller compaction, slugging and pneumatic dry granulation. Preferably, dry-granulation is performed.

In an embodiment, the granulator in which the mixture is granulated is equipped with a chopping means such as a chopper with, for example, relatively small-sized rotating blades for agglomerating the compounds and chopping the agglomerated or largely granulated particles. This enhances the granulation of the particles into a desirable uniform shape and size.

The particle size distribution of the granules after granulation may be relatively large, and therefore, the resultant granules should preferably be sieved in order to make a selection based on the size of the granules, to obtain granules suitable for use as a feed supplement for ruminants. Preferably, the resulting granules are sieved with one or more sieves having a mesh size of maximum 10. In this way, the selected granules will not have an average particle size larger than 2 mm.

When the particle size of the final product is too large, the granules are sometimes crushed. This allows the recovery of granules which did not pass the sieving step, thereby reducing the amount of unused or lost resources. Evidently, the latter is economically advantageous.

Potentially, the particle size of granules may be too small, causing incomplete coating of the granules in a further step of the method, thereby failing to provide rumen-bypass characteristics to the resultant coated granules. The reason for the potentially incomplete coating is that the small-sized fine particles are likely to agglomerate such that the particles become irregular, thus resulting in granule particles that are difficult to coat.

The resultant granules are dried to a moisture content of equal to or less than 1 wt%. This is crucial to the present invention, as this increases the stability and bioactivity of the choline chloride substantially, as compared to methods known in the art.

The moisture content of the mixture may be determined by any method known to a skilled person, for example, it can be determined by drying a product or composition for at least 12 hours at approximately 40°C, wherein the proportion of the pre-drying mass diminished with the post-drying mass over the post-drying mass represents the moisture content of said product or composition.

More in particular, said granules are dried at a temperature of between 60°C and 110°C, more preferably between 65°C and 105°C, and most preferably between 70°C and 100°C.

In another or further embodiment of the method, the granules are matured prior to coating said granules. Herein, the terms 'matured', 'maturing' and 'maturated' refer to a process wherein the granules are left to rest at a temperature of between 18°C to 25°C, preferably approximately 23°C. Evidently, maturing of the granules occurs in an environment having a moisture content of maximum 1 wt%. This maturation step allows the stabilization of the granules such that coating of these granules is optimized.

In ruminants, most of the vitamins ingested through feeding, are broken down during ’pre-digestion' in the rumen. Ingested vitamins therefore almost never get into the blood of these ruminants, and thus, do not contribute to the health, fitness and/or well-being of the ruminant.

It is therefore preferred to coat the dried granules with one or more fats. Coating the granules with one or more fats improves the stability of the granules in the rumen. As a consequence, such coated granules can resist rumen degradation, and the granules are able to deliver the choline chloride post-rumen, preferably to the abomasum and downstream thereof, and eventually to the small intestine where choline chloride is taken up into the blood. Hence, coating of the granules is crucial to protect hygroscopic choline chloride from rumen fermentation, and to enable delivery of the choline chloride to the post-rumen portion of the digestive tract such that the choline chloride can be taken up in the blood circulation of ruminants. Between the granulation step and the coating process, the granules are stored in a dry and cold atmosphere. Preferably, said atmosphere has a moisture content of less than 10%, preferably less than 5%, such as less than 4%, less than 3%, less than 2%, less than 1% or less than 0.5%. Preferably said atmosphere has a temperature of less than 15°C, preferably less than 10°C, such as 9°C, 8°C, 7°C, 6°C, 5°C, 4°C, 3°C, 2°C or 1°C.

Herein, it is important to note that choline chloride is bioactive only when taken up in the blood of the ruminant. The terms bioactive' and ’bioactivity' are used herein to denote a health or nutrition effect, and not only the energy value of for example fat or carbohydrates. Alternatively, it is possible to add further biologically active compounds during granulation and/or coating of the granules, to produce granules with two or more active ingredients.

Furthermore, the coating provides an odor and moisture barrier for the core. Specifically, the coat hinders the release of odors from the core, and prevents the core - and thus, the choline chloride - from taking up moisture from the environment. In this way, the sometimes unappealing odor of choline chloride does not affect the feed uptake and/or the feeding pattern of ruminants, nor does the stability and activity of the choline chloride become affected through an increase in the moisture content.

Coating of the granules may be performed by any process known to a person skilled in the art, for example by adding a molten coating composition to the granules. In such coating method, 20 to 40 parts, preferably 20 to 30 parts by weight of the molten coating composition is added, based upon 100 parts by weight of the granules. As used herein, the term 'coating composition' refers to a composition comprising at least one hydrophobic coating agent, wherein said hydrophobic coating agent is a fat.

Other coating processes may include for example spray drying, melt extrusion, coacervation, freeze drying, drum drying, belt drying, tray drying, tunnel drying or any combination thereof.

When the amount of the molten coating composition is too small, it is difficult to obtain the preferable coating film sufficient to bypass the rumen. Contrary to this, when the amount is too large, the choline chloride content in the granules becomes undesirably small. According to the present invention, the coating composition may comprise one or more excipients, such as for example a solubility modifier. When the ratio of the coating agent to the solubility modifier is too large, the solubility in the abomasum becomes undesirable. Alternatively, when the ratio is too small, a defective coating is formed and the durability in the rumen is spoiled.

The granules may be coated by any fat suitable for coating, known by a person skilled in the art. Suitable fats for coating the granules are e.g. glyceride esters of fatty acids, alkyl esters of fatty acids, fatty acids, hydroxyl fatty acid analogues of the above, fatty alcohols (like waxes) and mixtures thereof. Fatty acids generally have a number of carbon atoms of 12 or higher, preferably of 16 or higher such as for example 18, 20 and/or 22 carbon atoms. Suitable fatty acids include hydroxy- fatty acids. Preferably, the fatty acid derivative is a triglyceride ester of fatty acids, and more preferably it is the harder fraction of vegetable oils. Preferably, the fatty acids or fatty acid esters have a melting point of about 50°C or higher, preferably 57°C or higher. Generally, the melting point will be about 120°C or lower, preferably 100°C or lower.

Preferably, the granules are coated with one or more fats chosen from the group comprised of (at least partially hydrogenated) soybean oil, (at least partially hydrogenated) palm oil, carnauba wax, (at least partially hydrogenated) coconut oil, candelilla wax, bees wax, (at least partially hydrogenated) cottonseed oil, (at least partially hydrogenated) canola oil, (at least partially hydrogenated) corn oil, (at least partially hydrogenated) olive oil, and any mixture thereof. Most preferably, the granules are coated with at least partially hydrogenated soybean oil.

Although there are no critical limitations to the amount of the one or more fats in the coating or coating composition, the preferable amount is 50% to 100% by weight, more preferably, 75% to 100% by weight of the coating.

The coating process is performed under conditions such that the granules do not absorb moisture from the environment, atmosphere and/or the molten coating composition.

The molten coating composition needs to be solidified in order to shield the core of the coated granules from the environment, and eventually from the rumen digestion to allow the core to bypass the rumen when ingested by ruminants. Therefore, after applying the molten coating composition to the granules, the granules are cooled to a temperature of between 5°C to 25°C.

When coated, the resultant granules may be dried to reduce moisture content. In this way, the coated granules are prevented from clumping together, the durability of the coated granules may be enhanced, and the shelf life can be prolonged. This drying is preferably performed in an atmosphere having a low relative humidity, such as less than 10%, more preferably less than 5% such as less than 4%, 3%, 2% or 1%. In addition, it is important to keep the coated granules at a temperature lower than the melting temperature of fat coating. Preferably, the coated granules are kept at a temperature of between 5°C and 25°C, such as at room temperature.

To assess whether the resultant coated granules meet the regulations, and the predetermined specifications, said resultant granules are subjected to quality analysis. Preferably, the resultant coated granules are subjected to a classical sieving analysis, whereby the one or more sieves have a maximum mesh size of 10. In another or further embodiment, said granules may be subjected to a weighing analysis. During the quality analysis, one or more coated granules which do not meet the regulations and/or predetermined specifications are isolated and discarded. Additionally, the coated granules may be analyzed chemically and microbially to investigate whether the coated particles meet the regulations.

Coated granules which pass the quality analysis can be packaged. Preferably, the packaging is performed in an atmosphere having a relative humidity of 10% or less, preferably 5% or less, more preferably 4% or less, such as less than 3%, less than 2% or less than 1%. More preferably, the packaging material functions as a moisture-barrier such that the packaged granules are shielded from environmental humidity. In addition, the packaging may function as an odor-barrier. Examples of such packaging material are polyethylene and polypropylene.

In a second aspect, the invention provides a feed supplement comprising fat-coated choline chloride granules. Said granules are preferably obtainable by a method according to the present invention and comprise a core comprising choline chloride, and at least one fat coating. The core of the granules comprises a moisture content of 1 wt% or less.

Such fat-coated granules are able to deliver choline chloride to the abomasum in ruminants, thereby bypassing the rumen. Furthermore, the inventors of the present invention have found that a moisture content of 1% or less substantially increases the stability, the bioavailability and the bioactivity of choline chloride. Although it was known that choline chloride is a hygroscopic substance, it is not known in the prior art that such moisture content increases the bioactivity, bioavailability and the stability of choline chloride.

As a consequence, a feed supplement according to the present invention enables an increase in the uptake and activity of choline chloride, thereby allowing substantial reduction of the dosing of choline chloride. Evidently, the need for applying lower doses of choline chloride is economically advantageous. More in particular, the granules in a feed supplement according to the present invention exhibit an activity loss of less than 10%, preferably less than 5%, more preferably less than 2.5%, and most preferably less than 1%, such as 0.5% or 0.1% after rumen fermentation. Herein, the activity loss corresponds to a loss in activity of the choline chloride granules after rumen fermentation as compared to choline chloride granules which did not pass through the rumen, particularly due to degradation during rumen fermentation.

In a preferred embodiment, the core of granules in a feed supplement according to the present invention comprises 10-90 wt%, preferably 20-80 wt%, even more preferably 30-70 wt%, even more preferably 40-60 wt%, and most preferably approximately 50 wt% choline chloride.

The core of coated granules in a feed supplement according to the invention comprises a mixture of at least choline chloride and at least one binder. This allows alternating the dosing of choline chloride in the coated granules, for example depending on the application for which it will be used.

The core or the core mixture may comprise one or more additional components, such as excipients. The excipients may for example be chosen from the group comprising fillers (lactose, cellulose powder, calcium diphosphate, microcrystalline cellulose, sugar alcohols, e.g. mannitol, sorbitol and starch), disintegrants (starch (derivatives), croscarmellose, crosslinked PVP, carboxymethyl cellulose), lubricants (stearic acid, magnesium stearate), glidants (silicon dioxide (aerosil)), colorants, flavoring agents, or any mixture thereof.

The granules in a feed supplement according to the invention preferably have a particle size of maximum 2 mm, preferably more than 0.1 mm. Such particle size is desirable, for example because such particle size provides simple manipulation for the user and an easy miscibility with feed compositions.

Preferably, the granules in the feed supplement are stable at about 50°C or higher for improved storage stability. In a more preferred embodiment, the granules are stable up to 55°C or higher and even more preferably up to about 60°C or higher, such that the granules withstand the temperature at which calf-milk is prepared (about 56-60°C). The upper limit of the stability is not critical, but generally, at a temperature of about 150°C, the product will degrade, and a stability temperature of about 10°C or less will be sufficient in most cases. Stable means in this context, that the granules remain integral particles if kept for 10 min in water at the test temperature. Stability at elevated temperature is also important to withstand temperatures during extrusion and/or pelletizing. In pelletizing feed products often temperatures of up to 90°C are reached for several seconds.

The present invention may be described by the following embodiments: 1. A method for producing coated choline chloride granules for use as a feed supplement, the method comprising the steps of: - providing feed-grade choline chloride, said choline chloride being provided as a powder having an average particle size of 80-150 pm, - mixing said choline chloride with one or more binders, thereby obtaining a mixture; - granulating the dried mixture, thereby obtaining granules; - drying said granules; and - coating said granules with one or more fats, thereby obtaining fat coated choline chloride granules; characterized in that said granules are dried at a temperature of between 70 to 100°C to a moisture content of less than 1 wt%. 2. Method according to previous embodiment 1, wherein choline chloride is mixed with said one or more binders in a ratio between 10:90 and 90:10, preferably between 20:80 and 80:20, more preferably between 30:70 and 70:30, even more preferably between 40:60 and 60:40, and most preferably approximately 50:50. 3. Method according to any of the previous embodiments 1 to 2, wherein the granules are matured prior to coating said granules. 4. Method according to any one of the previous embodiments 1 to 3, wherein the one or more binders are selected from the group comprising of talc, cellulose, carboxymethylcellulose, methylcellulose, ethylcellulose, gelatin, polyvinylpyrrolidone, agar-agar, lactose, and any mixture thereof. 5. Method according to any of the previous embodiments 1 to 4, wherein the mixture is sieved prior to granulating. 6. Method according to previous embodiment 5, wherein the mixture is sieved with one or more sieves having a mesh size of maximum 10. 7. Method according to any of the previous embodiments 1 to 6, wherein the one or more fats are selected from the group comprising soybean oil, at least partially hydrogenated soybean oil, palm oil, at least partially hydrogenated palm oil, carnauba wax, coconut oil, at least partially hydrogenated coconut oil, candelilla wax, bees wax, cottonseed oil, at least partially hydrogenated cottonseed oil, canola oil, at least partially hydrogenated canola oil, corn oil, at least partially hydrogenated corn oil, olive oil, at least partially hydrogenated olive oil, and any mixture thereof. 8. Method according to previous embodiment 7, wherein the coating is partially hydrogenated soybean oil. 9. Method according to any of the previous embodiments 1 to 8, wherein the coated granules are sieved with one or more sieves having a mesh size of maximum 10. 10. A feed supplement comprising fat-coated choline chloride granules, said granules comprising a core comprising choline chloride, and at least one fat coating, characterized in that said granules are obtainable by a method according to any of embodiments 1-9, and wherein said granules comprise a moisture content of equal to or less than 1 wt%. 11. Feed supplement according to previous embodimentlO, wherein the core of said granule comprises 10-90 wt%, preferably 20-80 wt%, even more preferably 30-70 wt%, even more preferably 40-60 wt%, and most preferably approximately 50 wt% choline chloride. 12. Feed supplement according to any of the previous embodiments 10 to 11, wherein said granule has a particle size of between 0.1 mm and 2 mm. 13. Feed supplement according to any of the previous embodiments 10 to 12, characterized in that the granules exhibit a loss in activity of less than 5% after rumen fermentation.

The present invention will be now described in more details, referring to examples that are not limitative.

EXAMPLES

Example 1: Influence of moisture content on activity of coated choline chloride A dilution test was performed to illustrate the impact of moisture content in choline chloride granules (25% choline chloride, 10% starch) coated with hydrogenated soybean oil on the rumen stability of choline chloride. One gram of coated choline chloride granules having a defined moisture content was mixed in 100 ml water. The mixture was stirred for 12 hours, after which the mixture was filtered. The remaining (undissolved) dry matter and the concentration of choline therein was measured. Results are presented in Figure 1.

From the results presented in Figure 1, it is clear that the moisture content has a crucial impact on the stability of coated choline chloride. The lower the moisture content of the choline chloride product, the higher its stability in the rumen, and thus, the higher the bioavailability of choline chloride. It is observed that coated choline chloride granules having a moisture content of less than 1 wt% show sufficient stability to resist rumen fermentation, and thus, such coated granules show an optimal bioavailability in post-rumen portions of the digestive tract of ruminants where the choline chloride can be taken up in the blood of the ruminant.

Example 2: Method for producing coated choline chloride granules

This example pertains to a method for producing a feed supplement comprising fat-coated choline chloride granules suitable for use as a feed supplement for ruminants. 1 kg choline chloride in the form of a powder having an average particle size of 100 pm is mixed for 10 minutes with 1 kg talc powder having an average particle size of 12 pm. The mixture is then granulated by means of roller compaction to obtain granules. The resultant granules are then dried for 60 minutes at a temperature of 85°C thereby achieving a moisture content of 0.9%, and sieved by means of a sieve having a mesh size of 10. Sieving is performed in an atmosphere having a relative humidity of approximately 1%. Granules which do not pass through the sieve are weighed and recycled in a future production process. 200 grams of a coating composition consisting of hydrogenated soybean oil is melted and added to the granules in an atmosphere having a relative humidity of approximately 1%. The granules are carefully agitated through the molten coating composition such that the molten coating composition adheres to the granules, after which the coating composition is solidified to obtain coated granules.

The coated granules are then sieved by means of a sieve having a mesh size of 10, and then subjected to a weight analysis. Coated granules which do not pass the sieving analysis are discarded. The weight analysis takes into account the mass of granules which did not pass the sieve analysis, and gives an accurate estimation of the amount of moisture present in the coated granules, in this example the moisture content is equal to 0.9 wt% according to the weight of the granules.

The fat-coated granules are packaged in a moisture-impermeable and odorblocking polyethylene bag. Said packaging is performed in an atmosphere having a relative humidity of less than 5%.

Claims

A method to produce choline chloride granules coated for use as a feed supplement, the method comprising the following steps: Providing choline chloride suitable for consumption, wherein the choline chloride is provided as a powder with an average particle size of 80- 150 µm; Mixing the choline chloride with one or more binders, whereby a mixture is obtained; Granulating the dried mixture to obtain granules; Drying the grains; and Providing a coating around the granules with one or more fats, whereby a choline chloride granule with a fat coating is obtained; characterized in that the granules are dried at a temperature between 70 and 100 ° C to a moisture content of less than 1% of the total weight of the granules.

Method according to claim 1, wherein choline chloride is mixed with one or more binders at a ratio between 10:90 and 90:10, preferably between 30:70 and 70:30, more preferably between 40:60 and 60:40 , most preferably about 50:50.

Method according to claims 1 or 2, wherein the grains are aged before they are coated.

A method according to any one of the preceding claims 1 to 3, wherein one or more binders are selected from the group comprising talc, cellulose, caboxymethyl cellulose, methyl cellulose, ethyl cellulose, gelatin, polyvinyl pyrrolidone, agar agar, lactose or a mixture thereof.

The method according to any of the preceding claims 1 to 4, wherein the mixture is sieved prior to granulation.

Method according to claim 5, wherein the mixture is sieved with one or more sieves with a mesh size of a maximum of 10.

A method according to any one of the preceding claims 1 to 7, wherein one or more fats are selected from the group comprising soybean oil, at least partially hydrogenated soybean oil, palm oil, at least partially hydrogenated palm oil, carnauba wax, coconut oil, at least partially hydrogenated coconut oil, candelilla wax, beeswax, cottonseed oil, at least partially hydrogenated cottonseed oil, rapeseed oil, at least partially hydrogenated rapeseed oil, corn oil, at least partially hydrogenated corn oil, olive oil, at least partially hydrogenated olive oil, and any mixture thereof.

The method of claim 7, wherein the coating is at least partially hydrogenated soybean oil.

A method according to any one of the preceding claims 1 to 9, wherein the granules provided with a coating are sieved with one or more sieves with a mesh size of at most 10.

A feed additive comprising choline chloride granules provided with a fat coating, the granules comprising a core comprising choline chloride, and at least one fat coating, characterized in that the granules are obtainable by a method according to any one of claims 1 to 9, and wherein moisture content of the pellets is equal to or less than 1% on the total weight of the pellets.

A feed additive according to the preceding claim 10, wherein the amount of choline chloride in the core comprises 10-90%, preferably 20-80%, more preferably 30-70%, even more preferably 40-60% and most preferably 50% on the total weight of the grain.

A feed additive according to any one of the preceding claims 10 to 11, wherein the particle size of the grain is between 0.1 mm and 2 mm.

A feed additive according to any one of the preceding claims 10 to 12, characterized in that the granules exhibit a reduction in activity of less than 5% after rumen fermentation.