WO/2018/101662 | METHOD FOR PREPARING HARD CAPSULE AND HARD CAPSULE PREPARED THEREBY |
WO/2023/217589 | POLYAMIDE MICROCAPSULES |
WO/2008/120975 | ENCAPSULATING WITH THE AID OF A DOUBLE SUSPENSION |
SCHEX ROLAND (CH)
SCHAEFER CHRISTIAN (CH)
ZWICK THOMAS (CH)
URBAN KAI (CH)
WO2020093962A1 | 2020-05-14 | |||
WO2020093919A1 | 2020-05-14 | |||
WO2020093960A1 | 2020-05-14 | |||
WO2019185894A1 | 2019-10-03 | |||
WO2019185938A2 | 2019-10-03 | |||
WO2019185900A1 | 2019-10-03 | |||
WO2019185898A1 | 2019-10-03 | |||
WO2019185940A1 | 2019-10-03 | |||
WO2019185904A1 | 2019-10-03 | |||
WO2008080152A2 | 2008-07-03 | |||
WO2019185942A1 | 2019-10-03 | |||
WO2019185888A1 | 2019-10-03 |
US20180343909A1 | 2018-12-06 | |||
US20040209963A1 | 2004-10-21 | |||
US20190075831A1 | 2019-03-14 | |||
US20060115534A1 | 2006-06-01 | |||
CN109517080A | 2019-03-26 | |||
EP3478660A1 | 2019-05-08 | |||
EP0972777A2 | 2000-01-19 |
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Claims 1. A feed additive comprising a) at least a fat-soluble vitamin in an amount in the range of from 1 to 40 weight-%; b) at least a lignosulfonate in an amount in the range of 12 to 34.9 weight-%, preferably in an amount in the range of from 13 to 34.9 weight-%, more preferably in an amount in the range of from 15 to 34.9 weight-%; and c) at least a compound selected from hexose-dimers, modified hexose-dimers, hexose-oligomers, modified hexose-oligomers, hexose-polymers, modified hexose-polymers, and any mixture thereof in an amount of at least 10 weight-%; preferably at least two compounds selected from starch hydrolysates, starches and modified food starches, whereby at least one compound is different from starches, and any mixture thereof in an amount of at least 15 weight-%; wherein the lignosulfonate and the compound c) form a matrix in which the fat-soluble vitamin is encapsulated; wherein the amount of ethoxyquin in the feed additive is ≤ 0.5 weight-%; and wherein the amount of butylated hydroxytoluene in the feed additive is ≤ 0.5 weight-%, all amounts based on the total weight of the dry matter of the feed additive. 2. The feed additive according to claim 1, wherein the fat-soluble vitamin is vitamin A or a derivative thereof, vitamin D or a derivative thereof or any mixture thereof. 3. The feed additive according to claim 1 and/or 2, wherein the lignosulfonate is sodium lignosulfonate or calcium lignosulfonate or any mixture thereof. 4. The feed additive according to any one or more of the preceding claims additionally comprising an antioxidant. 5. The feed additive according to any one or more of the preceding claims additionally comprising a powder-coating agent. 6. The feed additive according to claim 5, wherein the feed additive comprises the fat-soluble vitamin in an amount in the range of from 5 to 35 weight-%, the lignosulfonate in an amount in the range of from 10 to 45 weight-%, the compound c) in an amount in the range of from 15 to 70 weight-%, the antioxidant in an amount in the range of from 0.05 to 15 weight-%, the powder- coating agent in an amount in the range of from 1 to 30 weight-%, and residual moisture in an amount in the range of from 0 to 10 weight-%, all amounts based on the total weight of the feed additive. 7. A process for the manufacture of a feed additive according to any one or more of the preceding claims comprising the following steps: i) Providing a matrix by dissolving the lignosulfonate and the compound c) and optionally a water-soluble antioxidant in water; ii) Providing an active phase by heating the fat-soluble vitamin and optionally the fat-soluble antioxidant, and if, present, an oil; iii) Dispersing the active phase obtained in step ii) into the matrix obtained in step i) to obtain a dispersion; iv) Drying said dispersion obtained in step iii), preferably in presence of a powder-coating agent, to obtain the feed additive. 8. A dispersion as obtained after having performed step iii) of the process according to claim 7. 9. A dispersion comprising a) at least a fat-soluble vitamin; b) at least a lignosulfonate; and c) at least a compound selected from hexose-dimers, modified hexose-dimers, hexose-oligomers, modified hexose-oligomers, hexose-polymers, modified hexose-polymers, and any mixture thereof in an amount of at least 10 weight-%; d) at least an antioxidant in an amount in the range of from 0 to 15 weight-%; wherein the lignosulfonate(s) and the compound c) form a matrix in which the fat-soluble vitamin is encapsulated; wherein the amount of ethoxyquin in the dispersion is ≤ 0.5 weight-%; and wherein the amount of butylated hydroxytoluene in the dispersion is ≤ 0.5 weight-%, whereby all amounts are based on the total weight of the dry matter of the feed additive. 10. Feed comprising a feed additive according to any one or more of claims 1 to 6. 11. The feed according to claim 10 being a milk replacer for calves, foals, young goats, young sheep and camel foals. 12. The feed according to claim 10 being feed for poultry further comprising cereals, minerals, vegetable oils, amino acids and proteins. 13. The feed according to claim 10 being feed for swine further comprising corn, micronutrients and amino acids. 14. The feed according to claim 10 being pet food for dogs and cats further comprising meat, vegetable proteins, grains, fiber sources, fats and/or oils, and micronutrients. 15. Use of the feed additive according to any one or more of claims 1 to 6 or the feed according to any one or more of claims 10 to 14 for supplementing said fat-soluble vitamin(s) to an animal excluding humans. 16. A method of supplementing said fat-soluble vitamin(s) to an animal excluding humans by administering a feed additive according to any one or more of claims 1 to 6 or a feed according to any one or more of claims 10 to 14 to said animal. |
Further examples of suitable antioxidants that can be used in the feed additives of the present invention are compounds of formula (III) and (IV), wherein R 1b and R 2b are independently from each other H or C1-11-alkyl or (CH2)n─OH with n being an integer from 1 to 6 or R 1b and R 2b together represent a keto group, and wherein R 3b , R 4b , R 5b , and R 6b are independently from each other H or C 1-6 -alkyl or C1-6-alkoxy, and R 7b is H or C1-6-alkyl, as disclosed in WO 2019/185898. “alkyl” and “alkoxy” hereby encompass linear alkyl and branched alkyl, and linear alkoxy and branched alkoxy, respectively. Preferred examples of compounds of formula (III) and (IV) are the following compounds (12)-(19): Further suitable antioxidants are compounds of formula (V), whereby R 1 , R 2 and R 3 are independently from each other H or linear C1-6-alkyl or branched C3-8-alkyl, whereby preferably R 1 is H or methyl or ethyl or n-propyl or iso-propyl or tert-butyl and R 2 and R 3 are independently from each other H or methyl or ethyl, with the further preferences as disclosed in WO 2019/185940.
Also, the compounds of formula (VI) with n being 1 or 2, R 1b and R 3b being independently from each other H or C1-5-alkyl, and R 2b being either H or C1-5-alkyl or C1-5-alkyloxy, preferably with the proviso at least one of R 1b , R 2b and R 3b being H, as disclosed in WO 2019/185904 can be used as antioxidants in the feed additives of the present invention. Hereby the following compounds of formulae (VI-1) and (VI-2) are especially preferred: The asterisks * mark each a chiral/stereogenic center, i.e. all possible isomers having any configuration at said centers are encompassed by the term “compound of formula (VI-1)” and “compound of formula (VI-2)”, respectively. Further suitable antioxidants are gallic acid derivatives such as the ones disclosed in WO 2008/080152, hydroxycinnamic acids such as e.g. ferulic acid (= 3-(4-hydroxy- 3-methoxyphenol)prop-2-enoic acid), hydroxycoumarines, hydroxybenzoic acids such as e.g. gallic acid (= 3,4,5-trihydroxybenzoic acid) and syringic acid (= 4-hydroxy- 3,5-dimethoxy-benzoic acid), propyl gallate, rosmarinic acid and carnosic acid. Also suitable fat-soluble antioxidants are compounds of the following formulae (VII) and (VIII) with R 1c , R 2c and R 3c being independently from each other H or C 1-4 -alkyl as published in WO 2019/185942 and WO 2019/185888, respectively. Preferred examples thereof are tocotrienols and tocopherols of the formulae (20) to (27) as shown below. The asterisks * mark each a chiral/stereogenic center. The term “compound of formula (VII)/(VIII)” encompasses all possible isomers having any configuration at said centers. Especially preferred examples of the compound of formula (VII) are the following compounds of formulae (20) (= alpha-tocotrienol), (21) (= beta-tocotrienol), (22) (= gamma-tocotrienol) and (23) (= delta-tocotrienol), whereby all possible diastereomers and enantiomers are included. Especially preferred examples of the compound of formula (VIII) are the following compounds of formulae (20) (= alpha-tocopherol), (21) (= beta-tocopherol), (22) (= gamma-tocopherol) and (23) (= delta-tocopherol), whereby all possible diastereomers and enantiomers are included. The asterisks * mark each a chiral/stereogenic center. The term “compound of formula (20)/(21)/(22)/(23)/(24)/(25)/(26)/(27)” encompasses all possible isomers having any configuration at said centers. The most preferred fat-soluble antioxidant is ^-tocopherol, especially DL- ^- tocopherol. In case the fat-soluble vitamin is vitamin E, the vitamin E may itself act as antioxidant, so that the amount of vitamin E is increased accordingly. Water-soluble antioxidants In general any water-soluble antioxidant being allowed in feed and known to the person skilled in the art may be used. Preferred examples of water-soluble antioxidants are ascorbic acid and salts thereof, such as alkali and earth alkali salts of ascorbic acid and ascorbyl-2- phosphate salts as disclosed in EP-A 972777. Especially preferred are alkali and earth alkali salts of ascorbic acid. The most preferred water-soluble antioxidant is sodium ascorbate. Most preferred antioxidants in the feed additive according to the present invention Most preferred is the use of ^-tocopherol as sole antioxidant in an amount ranging from 0.05 to 10 weight-%, preferably ranging from 0.1 to 7 weight-%, more preferably ranging from 0.5 to 5 weight-%, most preferably ranging from 1 to 3 weight-%, based on the total weight of the dry matter of feed additive. If a mixture of alpha-tocopherol and sodium ascorbate is used as antioxidant, the weight ratio of alpha-tocopherol to sodium ascorbate ranges preferably from 5:1 to 1:5, more preferably from 3:1 to 1:3, even more preferably from 2.5:1 to 1:2, most preferably from 2:1 to 1:1.5. If a mixture of alpha-tocopherol and ascorbic acid is used as antioxidant, the weight ratio of alpha-tocopherol to ascorbic acid ranges preferably from 5:1 to 1:5, more preferably from 3:1 to 1:3, even more preferably from 2.5:1 to 1:2, most preferably from 2:1 to 1:1.5. Feed additives according to the present invention The feed additive may be in liquid (= dispersion) or solid form. The composition of a preferred solid feed additive according to the present invention is shown in the following Table 1, where the ingredients and their amounts are given. The amounts are given in weight-% and are based on the total weight of the dry matter of the feed additive. The amounts of all ingredients sum up to a total weight of 100%. It is understood that each single preferred amount of one ingredient may be combined with each preferred single amount of any other ingredient. A preferred feed additive comprising a powder-coating agent is one, wherein the total amount of the compounds a) to d) is at least 90 weight-%, preferably at least 95 weight-%, preferably at least 97 weight-%, based on the total weight of the dry matter of the feed additive without the weight of the powder-coating agent. Table 1: Composition of a solid feed additive according to the present invention, whereby the feed additive comprises a powder-coating agent. All amounts except the residual moisture are based on the total weight of the dry matter of said feed additive. The amount of the residual moisture is based on the total weight of said feed additive. All amounts sum up to 100 weight-%.
Preferred embodiments of the feed additives according to the present invention Advantageously, the feed additives of the present invention do not comprise beeswax which is in discussion because of increasing levels of pesticide residues. Prefeably, the feed additives do also not comprise any ingredient from animal origin such as e.g. gelatin. The composition of preferred solid feed additives according to the present invention, which comprise a powder-coating agent, are listed in the following Table 2. The total amounts of all ingredients are based on the total weight of the feed additive and sum up to 100 weight-%. It is understood that each single preferred amount of one ingredient may be combined with each preferred single amount of any other ingredient. Table 2
Instead of dextrins, also glucose syrups or dried glucose syrups can be used together with modified OSA-starch. Further preferred feed additives according to Table 2 are feed additives, wherein the total amount of the compounds a) to d) is at least 90 weight-%, preferably at least 95 weight-%, preferably at least 97 weight-%, based on the total weight of the dry matter of the feed additive excluding the powder-coating agent. Especially preferred feed additives according to the present invention are the following ones, whereby all amounts sum up to 100 weight-%, based on the total weight of the dry matter of the feed additive: A) A feed additive comprising 15 to 25 weight-% of Vitamin A acetate or another vitamin A derivative; 25 to 34.9 weight-% of at least a lignosulfonate; 1o to 30 weight-%, preferably 13 to 20 weight-%, of at least a modified food starch; 1o to 30 weight-%, preferably 13 to 20 weight-%, of at least a dextrin or a glucose syrup or any mixture thereof, preferably of at least a dextrin; 1.0 to 4.5 weight- % of a fat-soluble antioxidant, preferably of dl- ^-tocopherol; 0 to 3.5 weight- % of a water-soluble antioxidant, preferably of sodium ascorbate or ascorbic acid; 5 to 12 weight-% of a powder-coating agent, preferably of silica or fluidized starch; all amounts based on the total weight of the dry matter of the feed additive, whereby preferably the weight ratio of the modified food starch to the dextrin/glucose syrup is 1.2 : 1 to 1 : 1.2, most preferably whereby the weight ratio of the modified food starch to the dextrin/glucose syrup is 1.05 : 1 to 1 : 1.05. (See examples 2, 3 and 5). B) A feed additive comprising 15 to 25 weight-% of Vitamin A acetate or another vitamin A derivative; 25 to 34.9 weight-% of at least a lignosulfonate; 1o to 20 weight-% of at least a modified food starch; 3 to 10 weight-% of at least a dextrin or a glucose syrup or any mixture thereof, preferably of at least a dextrin; 1.0 to 4.5 weight-% of a fat-soluble antioxidant, preferably of dl- ^- tocopherol; 0 to 3.5 weight-% of a water-soluble antioxidant, preferably of sodium ascorbate or ascorbic acid; 15 to 25 weight-% of a powder-coating agent, preferably of fluidized starch; all amounts based on the total weight of the dry matter of the feed additive, whereby preferably the weight ratio of the modified food starch to the dextrin/glucose syrup is 2.5 : 1 to 1.8 : 1. (See example 1). C) A feed additive comprising 13 to 23 weight-% of Vitamin A acetate or another vitamin A derivative; 8 to 18 weight-% of at least a lignosulfonate; 25 to 45 weight-%, preferably 30 to 40 weight-%, of at least a modified food starch; 3 to 15 weight-%, preferably 5 to 10 weight-%, of at least a dextrin or a glucose syrup or any mixture thereof, preferably of at least a dextrin; 10 to 15 weight- % of native starch; 1.0 to 4.5 weight-% of a fat-soluble antioxidant, preferably of dl- ^-tocopherol; 0 to 3.5 weight-% of a water-soluble antioxidant, preferably of sodium ascorbate or ascorbic acid; 5 to 20 weight-%, preferably 8 to 14 weight-%, of a powder-coating agent, preferably of silica or fluidized starch; all amounts based on the total weight of the dry matter of the feed additive, whereby preferably the weight ratio of the modified food starch to the dextrin/glucose syrup is 5 : 1 to 4 : 1. (See example 4). D) A feed additive comprising 15 to 25 weight-% of Vitamin A acetate or another vitamin A derivative; 30 to 40 weight-% of at least a lignosulfonate; 1o to 25 weight-%, preferably 13 to 22 weight-%, of at least a modified food starch; 1o to 25 weight-%, preferably 13 to 22 weight-%, of at least a dextrin or a glucose syrup or any mixture thereof, preferably of at least a dextrin; 1.0 to 4.5 weight- % of a fat-soluble antioxidant, preferably of dl- ^-tocopherol; 0 to 3.5 weight- % of a water-soluble antioxidant, preferably of sodium ascorbate or ascorbic acid; 0.1 to 2.5 weight-% of an anti-caking agent, preferably of silica; all amounts based on the total weight of the dry matter of the feed additive, whereby preferably the weight ratio of the modified food starch to the dextrin/glucose syrup is 1.2:1 to 1:1.2, most preferably whereby the weight ratio of the modified food starch to the dextrin/glucose syrup is 1:1. (See example 6). These preferred feed additives comprise residual moisture in the amount as disclosed above. Especially preferred embodiments thereof do consist only of the ingredients given above and do not comprise any further ingredients except of residual moisture, preferably in the amount as cited above. If the feed additives are liquid, the amounts of their ingredients have to be adjusted accordingly to obtain feed additives with the same relative amounts of the feed additives (see also Tables 1 and 2). The amount of water in said liquid feed additives is preferably in the range of from 35 to 70 weight-%, more preferably in the range of from 40 to 65 weight-%, even more preferably in the range of from 45 to 60 weight- %, most preferably in the range of from 50 to 55 weight-%, based on the total weight of the liquid feed additive. Processes of the present invention The present invention is also directed to a process for the manufacture of a feed additive with all the preferences as cited above comprising the following steps: i) Providing a matrix by dissolving the lignosulfonate and the compound c) and optionally a water-soluble antioxidant in water; ii) Providing an active phase by heating the fat-soluble vitamin(s) and optionally the fat-soluble antioxidant(s), and if, present, an oil; iii) Dispersing the active phase obtained in step ii) into the matrix obtained in step i) to obtain a dispersion; iv) Drying said dispersion obtained in step iii), preferably in presence of a powder-coating agent, to obtain the feed additive. The feed additive may be used in liquid or in solid form. The liquid form is obtained after step iii), the solid form after step iv). Preferably the feed additive of the present invention is used in solid form. The single steps are disclosed in more detail below. Step i) The amounts of the lignosulfonate b), the compound c) and the water-soluble antioxidant d), if present, are chosen so that the final amounts of these compounds in the resulting dispersion or feed additive after having performed steps i) to iii) and i) to iv), respectively, is as described above. Preferably this step is performed at a temperature in the range of from 25 to 85°C, more preferably at a temperature in the range of from 30°C to 80°C, even more preferably at a temperature in the range of from 40°C to 75°C, most preferably at a temperature in the range of from 50°C to 70°C. Step ii) The amounts of the fat-soluble vitamin a) and the fat-soluble antioxidant d), if present, and the oil, if present, are chosen so that the final amounts of these compounds in the resulting dispersion or feed additive after having performed steps i) to iii) and i) to iv), respectively, is as described above. Preferably the dissolution temperature is chosen so as to dissolve the fat-soluble vitamin a) and the fat-soluble antioxidant d), if present, completely. Usually it is necessary to heat up the suspension obtained when mixing all compounds present in this step to get a solution. If Vitamin A and/or a derivative thereof is the fat- soluble vitamin the heating is continued until the mixture is liquified. The temperature to which the mixture is heated up is e.g. in the range of from 40 to 90°C, more preferably the temperature is in the range of from 50 to 80°C, most preferably the temperature is in the range of from 55 to 65°C. Step iii) Preferably this step, i.e. the mixing of the aqueous phase obtained in step i) and the active phase obtained in step ii), is performed at a mixing temperature in the range of from 30 to 70°C, more preferably at a mixing temperature in the range of 35 to 65°C, even more preferably at a mixing temperature in the range of 40°C to 60°C to obtain a dispersion. The dispersing step can be achieved by using a rotor-stator device or a high- pressure homogenizer or both. Other devices known to the person skilled in the art may also be used. If rotor-stator device and/or a high-pressure homogenizer is used, a pressure drop in the range of 70 to 1000 bar, more preferably in the range of 100 to 300 bar, is preferably applied. Step iv) By the drying step the dispersion is converted into a solid form. The conversion to the solid form can be achieved by any method known to the person skilled in the art where a powder-coating agent is used, preferably by a powder-catch technique, whereby the sprayed dispersion droplets are caught by a powder-coating agent (so-called “catch media”), such as e.g. silica or starch, and dried. Suitable powder coating agents include corn starch, as well as starches from other botanical sources, silica, modified silica, tricalcium phosphate, calcium carbonate, sodium carbonate, potassium carbonate, magnesium carbonate, calcium oxide, magnesium oxide, dicalcium diphosphate, calcium silicate, magnesium silicate, magnesium trisilicate, sodium aluminum silicate, talc, kaolin, calcium stearate, magnesium stearate, cellulose or mixtures thereof. Especially preferred are starch (i.e. corn starch as well as starches from other botanical sources), silica, tricalcium phosphate and hydrophobically modified silica, whereby corn starch or starches from other botanical sources such as waxy corn, wheat, tapioca, pea and potato are especially preferred. In another embodiment of the present invention, the conversion to the solid form can be achieved by any method known to the person skilled in the art where no adsorbent or powder-coating agent is used, e.g. by spray-drying, spray-drying in combination with fluidised bed granulation. The resulting feed additive does neither comprise an adsorbent nor a powder-coating agent; the amounts of the ingredients and their ranges are the same as given above, but based on the total weight of the feed additive without the weight of the adsorbent and without the weight of a powder-coating agent. In an embodiment of this solid form, 0.1 to 2.0 weight-% of an anti-caking agent may be used, based on the total weight of the feed additive including the weight of said anti-caking agent. As anti-caking agent the compounds as mentioned above as examples of powder-coating agents may be used, especially any form of silica as mentioned above. Characteristics of the feed additives of the present invention Preferably the inner phase of the feed additive according to the present invention, i.e. the inner phase of the liquid feed additive after step iii) or the inner phase of the solid feed additive after step iv), when re-dispersed in deionized water, has a median particle size [D50] in the range of from 100 to 1000 nm, preferably in the range of from 120 to 650 nm, more preferably in the range of from 150 to 400 nm, measured via laser diffraction (red and blue light laser) using especially the particle analyzer Malvern Mastersizer 3000 (Malvern Panalytical, Worcester, UK) and the following parameters: Dispersant Refractive Index: 1.330 ; Particle Refractive Index: 1.456 ; Particle Absorption Index: 0.000 ; Scattering Model: Mie; Analysis Model: General Purpose; i.e. the particles have an average diameter according to volume distribution within the ranges as given above. Preferably the particle size D[50] of the spray-dried final powder is in the range of from 30-200 µm, preferably 50-150 µm, more preferably 75-125 µm measured via laser diffraction (red light laser) using the particle analyzer Malvern Mastersizer 3000 (Malvern Panalytical, Worcester, UK) and the following parameters: Dispersant Refractive Index: 1.000; Particle Refractive Index: 1.000 ; Particle Absorption Index: 0.000 ; Scattering Model: Fraunhofer; Analysis Model: General Purpose; i.e. the particles have an average diameter according to volume distribution within the ranges as given above. Preferably the particle size D[50] of the powder-catch final powder is in the range of from 100-800 µm, preferably 150-600 µm, more preferably 200-450 µm measured via laser diffraction (red light laser) using the particle analyzer Malvern Mastersizer 3000 (Malvern Panalytical, Worcester, UK) and the following parameters: Dispersant Refractive Index: 1.000; Particle Refractive Index: 1.000 ; Particle Absorption Index: 0.000 ; Scattering Model: Fraunhofer; Analysis Model: General Purpose; i.e. the particles have an average diameter according to volume distribution within the ranges as given above. The formulations of the present invention show preferably a bulk density ranging from 0.38-0.70 g/cm 3 . Furthermore, the formulations of the present invention show preferably a tap density ranging from 0.50-0.80 g/cm 3 . The bulk density and the tap density are measured as follows: A 250 ml glass cylinder is filled with the sample. The volume and the weight are measured. Bulk density is the weight divided by the volume. For measuring the tap density the sample is tapped with a 2000 Taps with a Stampfvolumeter JEL STAV II (J. Engelsmann AG). The tapped volume is measured. Tap density is the weight divided by the tapped volume. These bulk and tap densities guarantee a good homogeneity of the feed additive according to the present invention in feed and feed premixes, especially in milk replacers especially for mammals such as calves, foals, young goats, young sheep and camel foals. “Young” in this context means the time from birth of the mammal until the mammal would be lactated by its mother. A milk replacer is especially a powder, which is dissolved in water, and administered to young mammals, such as preferably calves, foals, young goats, young camels and young sheep, instead of milk from the animals’ mother. The milk replacer preferably contains essential nutrients including proteins, amino acids, carbohydrates, fats, vitamins and minerals. Thus, another embodiment is also a milk replacer, especially as described above, comprising a feed additive according to the present invention. Dispersions according to the present invention The present invention is also directed to the dispersion as obtained after having performed step iii) as well as to the following dispersion comprising: - at least a fat-soluble vitamin; - at least a lignosulfonate; - at least a compound selected from hexose-dimers, modified hexose- dimers, hexose-oligomers, modified hexose-oligomers, hexose-polymers, modified hexose-polymers, and any mixture thereof in an amount ≥ 10 weight-%; preferably at least two compounds selected from starch hydrolysates, starches and modified food starches, whereby at least one compound is different from starches, and any mixture thereof in an amount of at least 15 weight-%; - at least an antioxidant in an amount in the range of from 0 to 15 weight-%; wherein the amount of ethoxyquin in said dispersion is ≤ 0.5 weight-%; and wherein the amount of butylated hydroxytoluene in said dispersion is ≤ 0.5 weight-%; all amounts based on the total weight of the dry matter of said dispersion. The amount of water in the dispersion is chosen in such a way so that its final amount in the dispersion is preferably in the range of from 40 to 65 weight-%, more preferably its final amount is in the range of from 45 to 60 weight-%, most preferably its final amount is in the range of from 50 to 55 weight-%, based on the total weight of the dispersion. The amount of the fat-soluble vitamin in the dispersion is chosen in such a way so that its final amount in the dispersion is preferably in the range of from 1.0 to 40 weight-%, more preferably its final amount is in the range of from 5.0 to 35 weight- %, even more preferably its final amount is in the range of from 10 to 30 weight-%, most preferably its final amount is in the range of from 15 to 25 weight-%, based on the total weight of the dry matter of the dispersion. The amount of the lignosulfonate is chosen in such a way so that its final amount in the dispersion is preferably in the range of from 12 to 34.9 weight-%, more preferably its final amount is in the range of from 13 to 34.9 weight-%, most preferably its final amount is in the range of from 15 to 34.9 weight-%, based on the total weight of the dry matter of the dispersion. The amount of the compound c) is chosen in such a way so that its final amount in the dispersion is preferably in the range of from 15 to 70 weight-%, more preferably its final amount is in the range of from 20 to 65 weight-%, most preferably its final amount is in the range of from 20 to 45 weight-%, based on the total weight of the dry matter of the dispersion. The total amount of the antioxidant is chosen in such a way so that its final amount in the dispersion is preferably in the range of from 0.1 to 12 weight-%, more preferably its final amount is in the range of from 0.5 to 10 weight-%, most preferably its final amount is in the range of from 1 to 8 weight-%, based on the total weight of the dry matter of the dispersion. The particle sizes of the dispersion are the same as given above for the inner phase of the solid/dried feed additive. The preferences for the ingredients a) to c), the antioxidant and the powder- coating agent also apply here. The viscosity of the dispersion with a water content in the range of from 40-65 weight-%, preferably 40-60 weight-%, measured at 65°C with a Kinexus viscosimeter (Malvern Panalytical, Worcester, UK) at a shear rate of 100/sec and with a Cylinder C25 (DIN), is preferably in the range of from 80 to 1000 cPs (= mPas), more preferably in the range of from 300-600 cPs, most preferably in the range of from 400 to 500 cPs. It is understood that the present invention encompasses any possible combination of any preference(s) with any other preference(s). Feed according to the present invention The present invention is also directed to feed comprising the feed additive according to the present invention with the preferences as given above. Feed (or ‘feedingstuff’) means any substance or product, including additives, whether processed, partially processed or unprocessed, intended to be used for oral feeding to animals. Feed in the context of the present invention is especially feed for broilers including starter, grower, finisher; broiler breeders including starter, grower (pullets), layers and male breeders, for layers and other poultry such as e.g. hens and duck layers, layers breeders, ducks and geese, partridges, quails and pheasants, ostrich and emu, for turkeys including starter, grower, finisher; for turkey breeders including starter, grower, layers and male breeders, for ruminants including calves, milk replacer, heifers, beef cattle, breeding bulls, sheep and goats; for horses, especially foals, leisure horses, race horses, mares and stallions, for rabbits, for mick and foxes, for swine including fattening pigs: pre-starter, starter, grower, finisher; breeders: replacement gilts, sows, boars, and feed for companion animals, especially for dogs and cats. The amount of the feed additive and the fat-soluble vitamin respectively follows the regulatory guidelines in the regions depending on the specific animal species and its age. In the Supplementation Guidelines the amount of the vitamins A and D3 is given in International Units (“I.U.”). To ensure that the active content in the feed is communicated in a systematic way, “I.U.” is used as a universal unit for fat soluble vitamins because there are different forms of the vitamins with varying amounts of fat-soluble vitamins. The feed additive comprising the fat-soluble vitamin according to the present invention is usually added to feed in form of a premix, i.e. a mixture with other micro-nutrients such as other vitamins or their formulations and minerals. The premix inclusion in feed is < 1 weight-% for many species. Advantageously, feed additives according to the present invention comprising lignosulfonate(s), starch hydrolysates such as especially dextrins and modified food starch such as especially OSA starch show a brown color which makes them especially suitable for premixes which show the same color. Advantageously, feed additives according to the present invention comprising lignosulfonate(s), starch hydrolysates such as especially dextrins, modified food starch such as especially OSA starch and native starch, preferably in a weight ratio of (1-3) to 1 to (2-6) to (1-3), show a yellow color which makes them especially suitable for milk replacements for calves, foals, young goats, young sheep and camel foals, which show the same color. The amount of the feed additive comprising the fat-soluble vitamin needed to be included into the feed is calculated based on the active content of the feed and the targeted dosage of the fat-soluble vitamin in the final feed considering said inclusion level. The conversion factors of the fat-soluble vitamins are as follows: 1 I.U. Vitamin A corresponds to 0.344 μg of Vitamin A acetate; 1 I.U. Vitamin D 3 corresponds to 0.025 μg of Vitamin D 3 ; 1 g of Vitamin K3 (menadione) corresponds to 2.0 g of menadione sodium bisulfite (“MSB”) and to 2.3 g of menadione nicotin-amide bisulfite (“MNB”); 1 g of Vitamin E corresponds to 1.0 g of DL- ^-tocopheryl acetate. The following Table 3 shows the amounts of the fat-soluble vitamins added per kg of air-dry feed. The exact amount is depending on several factors such as phase/age of the animal, animal species and legal local limits. Table 3 Below are given non-limiting examples of feed to which the feed additives of the present invention may be added. Feed for poultry The feed for poultry differs from region to region. In the following Tables I and II typical examples for diets in Europe and Latin America are given. These diets include cereals such as wheat, rye, maize/corn, minerals such as NaCl, vegetable oils such as soya oil, amino acids and proteins. Thus, an embodiment of the present invention is also feed for poultry comprising the feed additive according to the present invention, cereals, minerals, vegetable oils, amino acids and proteins. Table I: European diet Table II: Latin American diet Pet food Pet foods are formulated to meet nutrient specifications using combinations of multiple ingredients to meet the targeted nutrient specification. Poultry meal e.g. is an ingredient that is commonly found in Dog and Cat foods. The nutrient specifications for a complete and balanced dog or cat food will meet or exceed the guidelines provided by AAFCO (American Association of Feed Control Officials). The ingredient composition of pet-food can include any legal feed ingredient so number of combinations are not quite infinite but close. Some examples of ingredient used in dog and cat foods can be found in Table III below: Table III:
A further embodiment of the present invention is pet food comprising meat, vegetable proteins, grains, fiber sources, fats and/or oils, micronutrients and a feed additive according to the present invention. Feed for Swine Reference is made here to the NATIONAL SWINE NUTRITION GUIDE, 2010, whereby two non-limiting examples are given below. Table IV: Corn and Soybean Meal Diet
Table V: High fiber ingredient diet Thus, another embodiment of the present invention is feed for swine comprising corn, micronutrients, amino acids and a feed additive according to the present invention. Further embodiments according to the present invention The present invention is also directed to the use of the feed additive according to the present invention with the preferences as given above for supplementing fat- soluble vitamin(s) to an animal, especially those cited above, excluding humans, as well as to the use of feed according to the present invention with the preferences as given above for supplementing fat-soluble vitamin(s) to an animal, especially those cited above, excluding humans. Further embodiments of the present invention are methods of supplementing fat- soluble vitamin(s) to an animal excluding humans by administering a feed additive according to the present invention with the preferences as given above or a feed according to the present invention with the preferences as given above to said animal. Hereby the supplementation of vitamin A acetate or vitamin D3 or both is especially preferred. The invention is now further illustrated in the following non-limiting examples. Examples Examples 1-6: Preparation of the feed additive according to the present invention comprising vitamin A acetate The used ingredients and their amounts are given in Table 4, the characteristics of the feed additives in Tables 5 and 6. As compound c) a mixture of an OSA starch and dextrin yellow is used, whereby additionally native starch may be present. As compound b) calcium lignosulfonate (as commercially available from Borregaard LignoTech, Norway) is used, as a fat-soluble antioxidant dl- α- tocopherol and as a water-soluble antioxidant sodium ascorbate or ascorbic acid. Compounds b), c) and the water-soluble antioxidant are dissolved in deionized water to obtain the so-called “matrix”. The crystalline vitamin A acetate and the fat-soluble antioxidant are heated at 65°C under stirring in a water bath until the complete melting of the crystals to obtain the so-called “active phase”. Subsequently, the active phase is pre-emulsified into the matrix at 5500 rpm by using a rotor-stator homogenizer. Afterwards, the emulsion is further emulsified at 6000 rmp for 30 minutes. Subsequently, the emulsion is sprayed into the catch medium (fluidized starch or silica). The solid formulation remains in the catch medium for 45-60 minutes to obtain beadlets. After drying the dried beadlets are sieved and the fraction with a particle size in the range of 160 to 630 µm is used for the further tests (stability, process loss etc. ).
T Example 4 Example 5 Example 6 (Powder-Catch) (Spray- drying) 17.5 19.6 19.6 12.8 31.4 35.32 35.3 16.5 18.54 7.7 16.5 18.54 12.8 — — 2.5 4.0 4.0 — 3.0 (ascorbic 3.0 (ascorbic acid) acid) 11.4 (fluidized 9.0 (fluidized 1.0 (silica) starch) starch) Vitamin A acetate stability during stress testing exposing prototypes to 40°C and 75% relative humidity (feed additives according to examples 1-4) Aliquots of 120 mg are weighed into perforated capped plastic tubes. Thus, the samples are exposed to the environment during storage for 4 and 8 weeks in climatized rooms at 40°C and 75% relative humidity. The total vitamin A acetate concentration is determined by HPLC (high performance liquid chromatography) at the respective storage time. In brief, the aforementioned aliquot of 120 mg is transferred to a flask containing 200 mg BHT (butylated hydroxytyrosol). BHT prevents further degradation of the vitamin A acetate during the analytical procedure. Subsequently, the sample is re-dispersed in 10 mL deionized water at 50°C. After adding 100 mL ethanol and 80 ml dichloromethane, the mixture is kept for 30 min at room temperature. Afterwards, the sample is made up to 200 mL with dichloromethane and an aliquot of 10 mL is centrifuged for 5 min at 4000 rpm. The supernatant of the centrifuged stock solution is filled into amber glass vials for HPLC analysis. Vitamin A retentions are calculated based on the initial concentration. Each test is performed two times. The average of the results is shown in Table 5. The accuracy is ± 5%. The starting value is 100%. The results show that the feed additive of vitamin A acetate is stable under both conditions for at least 2 weeks. Process Loss To measure the vitamin A acetate process losses of solid particles the following procedure is followed: 100 mg dry beadlets are transferred in a 200 mL volumetric flask. 5 mL of 2 wt% ammonia solution (Merck Group, Germany) and 50 mg of amylase (Merck Group, Germany) are added in the flask. The flask is added in an ultrasound water bath for 10 min, set at 70°C. Afterwards, the flask is cooled down to room temperature Ethanol is added until the meniscus of the volumetric flask and then the flask is shaked smoothly, until a homogenous dispersion is obtained. 2 mL of the dispersion are then collected and injected in the HPLC. Color measurements Color measurements are performed with a colorimeter (Hunter Lab Ultra Scan Pro) which can other than a spectrophotometer express color values according to the psychophysical perception of color by human eye. Color measurements are carried out after CIE guidelines (Commission International d’Eclairage). Values can be expressed either as planar coordinates L*a*b* with L* being the measuring value for lightness, with a*being the value on the red-green- axis and with b* being the value on the yellow-blue-axis. Instrument settings: Color scale : CIE L*a*b* / L*C*h* Light source definition: D65 daylight equivalent Geometry : Diffuse / 10° Wavelengths: scan 400 to 800 nm Sample measurement area diameter: 19.812 mm (large) Calibration mode: Reflection including shining. Table 5
The particles sizes, the bulk and tap densities are measured as disclosed above and the results shown in the following Table 6. Table 6