Biocompatible, non-toxic additive

Abstract

A biocompatible, non-toxic additive for a core comprising: alkyl cellulose ether; and smectite is provided. The smectite is preferably bentonite. The alkyl cellulose ether may be methylcellulose, ethy

Description

The present invention relates to a biocompatible, non-toxic additive for an animal feed pellet, and a method for producing the biocompatible, non-toxic additive. The present invention also relates to a method for providing a pellet comprising the biocompatible, non-toxic additive. BACKGROUND OF INVENTION Trace element deficiency in grazing species of animals, including cattle, goats, sheep and deer, can lead to problems in reproduction, productivity in dairy herds, and other health issues such as disease. These deficiencies are often linked to low levels of trace elements in the animal's feed, especially in foraging animals whose trace element intake is dependent on the presence of these elements in the soil. These deficiencies can also move up the food chain into humans as a result of consuming both meat and milk. A convenient way of supplying these animals with minerals, vitamins or other dietary needs is by means of administering a slow release bolus. A bolus may be administered by mouth and fits in either of the first two stomach compartments of the animal. The supplement is released over a period of time. There is therefore a need for an improved method for addressing trace element deficiency in animals. There is a need for a biocompatible, non-toxic additive which is configured to provide for sustained supply of trace elements into an animal. There is a need for an improved method for providing a biocompatible, non-toxic additive for a core, such as a bolus. SUMMARY OF INVENTION According to a first aspect of the present invention, there is provided a biocompatible, non-toxic additive for a core (for example an animal feed pellet) comprising: alkyl cellulose ether; and smectite. The additive may for example be water insoluble or sparingly water soluble. The additive may be provided as a coating for applying to an outer surface of a core, for example of an animal feed pellet. The additive may be combined with components of a core, for example with components of an animal feed pellet, to provide an additive-containing core (for example additive-containing animal feed pellet). The smectite is present to enhance rigidity and brittleness of the additive. The presence of smectite therefore helps to control the rate of degradation of the additive-containing core or additive coating, and therefore the rate of release of the core. Preferably, the smectite comprises bentonite. Smectite and alkyl cellulose ether are approved for use with animal feeds and medicines by worldwide regulatory bodies such as US Food &Drug Administration (FDA). The alkyl cellulose ether may be any suitable alkyl cellulose ether. Preferably, the alkyl cellulose ether has a molecular weight in the range of between 40,000 AMW to 1,300,000 AMW (average molecular weight). For example, if the alkyl cellulose is ethyl cellulose, the molecular weight is preferably in the range of between 75KDa (75,000 AMW) and 400KDa (400,000 AMW), preferably between 150KDa (150,000 AMW) and 250KDa (250,000 AMW). In one embodiment, the alkyl group of the alkyl cellulose is a Ci-Cio alkyl group, preferably a C1-C5 alkyl group. The alkyl group of the alkyl cellulose is preferably selected from one or more of: methyl; ethyl; or any combination thereof. Preferably, the alkyl cellulose is ethyl cellulose. The alkyl group of the alkyl cellulose may be hydroxsubstituted. For example, the alkyl cellulose may comprise one or more of: hydroxypropyl cellulose; hydroxypropylmethyl cellulose, or any combination thereof. Preferably, the alkyl cellulose comprises hydroxypropyl cellulose. The additive may comprise a combination of alkyl cellulose ethers selected to provide the desired insolubility or sparing solubility of the additive in water. In one embodiment, the additive comprises ethyl cellulose and bentonite. Preferably, the alkyl cellulose is present within the additive in an amount of at least 10% w / w. The alkyl cellulose is preferably present within the additive in an amount of no more than 90% w / w. In one embodiment, the alkyl cellulose is present within the additive in an amount of between 30% and 70% w / w. Preferably, the alkyl cellulose is present within the additive in an amount of approximately 60% w / w. Preferably, smectite is present within the additive in an amount of at least 10% w / w. Smectite is preferably present within the additive in an amount of no more than 90% w / w. In one embodiment, smectite is present within the additive in an amount of between 20% and 80% w / w. Preferably, smectite is present within the additive in an amount of approximately 40% w / w. The additive may further comprise one or more active ingredients. The additive may for example comprise one or more plant based additives and / or heat sensitive additives. The additive when applied to a core, for example animal feed pellet, may reduce methane output from an animal, such as for example ruminant animals. A core may comprise a methane reducing additive, such as for example bromoform. The additive may be incorporated with the core or coated on the core, thereby reducing the rate of degradation of the core. The additive may therefore reduce the rate of release of the methane reducing additive. For example, the additive may be provided within or on a core to provide for sustained release of the methane reducing additive. The coating is preferably free from non-biodegradable components. Preferably, the coating is free from vinyl ester resin, for example free from styrene. The core is preferably a bolus. A bolus is an object containing and releasing predetermined supplement or medicine and is configured to release these ingredients at a predetermined rate to improve or maintain the health of the animal. A bolus may comprise predetermined trace elements. For example, a bolus may comprise one or more of: vitamin A, vitamin D, vitamin E, cobalt carbonate, zinc sulphate, calcium iodate, copper oxide, zinc sulphate, manganese sulphate, sodium selenite, biotin, or any combination thereof. The core, for example a bolus, may be configured to be administered directly into the rumen of an animal. The core, for example a bolus, together with the coating are configured to slowly break down over a predetermined time period. Preferably the coating (and optionally the core) is configured to break down, within for example the rumen of an animal, over a time period of at least 1 month, preferably at least 2 months, for example at least 4 months. Preferably, the coating (and optionally the core) is configured to break down, within for example the rumen of an animal, over a time period of no more than 1 year, preferably no more than 10 months, for example no more than 8 months. Preferably, the coating (and optionally the core) is configured to break down, within for example the rumen of an animal, over a time period of between 1 month and 1 year, preferably between 2 months and 10 months, for example between 4 months and 8 months. According to second aspect of the present invention, there is provided a smectite incorporated alkyl cellulose-solvent mixture comprising: alkyl cellulose ether; smectite; and a solvent-system. Preferably, the solvent-system comprises at least one alkyl ester and at least one alcohol. The at least one alkyl ester preferably comprises at least one Ci-Cw alkyl ester, preferably at least one C2-C5 alkyl ester. The at least one alcohol preferably comprises at least one C1-C5 alcohol, preferably propanol. In one embodiment, the solvent-system comprises at least Ci-Cw alkyl ester and at least one C1-C5 alcohol. Preferably, the solvent-system comprises at least CrC6 alkyl ester and propanol. The ratio of the at least one alkyl ester to the at least one alcohol in the smectite incorporated alkyl cellulose-solvent mixture is preferably at least 2:1. Preferably, the ratio of the at least one alkyl ester to the at least one alcohol in the smectite incorporated alkyl cellulose-solvent mixture is no more than 8:1. In one embodiment, the ratio of the at least one alkyl ester to the at least one alcohol is in the range of from 3:1 to 6:1. The smectite incorporated alkyl cellulose-solvent mixture may be applied to a core, for example animal feed, preferably an animal feed pellet. According to a third aspect of the present invention, there is provided a composition (for example an animal feed composition) comprising: a core (for example a pellet), and a biocompatible, non-toxic additive as herein described. The additive may be applied to an outer surface of the core. The additive may be combined within the core. In one embodiment, the additive is provided as a coating which substantially encapsulates the core. Preferably, at least a portion of the core remains free from contact with the additive, to enable the additive free portion of the core to be contacted by digestive fluids within the rumen of an animal. The additive requires the presence of the core to retain its integrity. For example the core may have an additive free end. As a result, when an underlying portion of the core has been dissolved, the overlying portion of the coating breaks away from the core exposing further portions of the core. As a result, the rumen fluid comes into contact with the further portions of the core causing the core to dissolve and to supply nutrients from the core to the animal. The core may comprise: a binder (for example magnesium stearate), a lubricant, and one or more trace elements. The binder, lubricant and trace elements are preferably mixed to form a homogenous mixture. The core may be compressed into a predetermined shape, for example under pressure. For example, the core may be cylindrical or spherical or disc shaped. The core may comprise a weight formed of material having a high overall specific gravity, for example an iron weight, to prevent regurgitation of the core by an animal. The core together with the additive may have any suitable dimensions. In one embodiment, the core together with the additive has a length of at least 50 mm, preferably at least 60 mm, for example 75 mm. Preferably, the core together with the additive has a length of no more than 100 mm, preferably no more than 80 mm. In one embodiment, the core together with the additive has a length of between 50 mm and 100 mm, preferably between 60 mm and 80 mm. The additive may be applied as a coating having any suitable thickness. Preferably, the coating has a thickness of at least 0.05 mm, preferably at least 0.1 mm. Preferably, the coating has a thickness of no more than 0.5 mm, preferably no more than 0.3 mm. In one embodiment, the coating has a thickness of between 0.1 mm and 0.3 mm. The duration of controlled release of the core may be controlled by one or more of: the composition of the additive, the amount of additive present, the thickness of the coating, the dimensions of the core, and / or the density of the core. According to a fourth aspect of the present invention, there is provided a method for the preparation of a biocompatible, non-toxic additive as herein described, comprising: dissolving alkyl cellulose in a solvent-system to provide an alkyl cellulose-solvent mixture; introducing smectite into the alkyl cellulose-solvent mixture to provide a smectite incorporated alkyl cellulose-solvent mixture; and evaporating the solvent from the smectite incorporated alkyl cellulose-solvent mixture to provide an additive. Preferably, the alkyl cellulose is dissolved in the solvent-system by high shear mixing. The smectite is preferably incorporated into the alkyl cellulose-solvent mixture under high shear. According to a further aspect of the present invention, there is provided a method for incorporating a biocompatible, non-toxic additive with a core (for example a pellet), the method comprising: dissolving alkyl cellulose in a solvent-system to provide an alkyl cellulose-solvent mixture; introducing smectite into the alkyl cellulose-solvent mixture to provide a smectite incorporated alkyl cellulose-solvent mixture; treating a core with the smectite incorporated alkyl cellulose-solvent mixture to provide a smectite-incorporated alkyl cellulose-solvent containing core; and evaporating solvent from the smectite-incorporated alkyl cellulose-solvent containing core to provide a core comprising a biocompatible, non-toxic additive. The smectite incorporated alkyl cellulose-solvent mixture may be applied as a coating to an outer surface of a core. The smectite incorporated alkyl cellulose-solvent mixture may be incorporated by mixing together with components which form the core. The core (for example the pellet) may be coated with the smectite incorporated alkyl cellulose-solvent mixture by dipping or spraying. The core (for example the pellet) is preferably coated with the smectite incorporated alkyl cellulose-solvent mixture by dipping. The core may be dipped or sprayed for a predetermined time period, for example for at least 2 seconds, preferably at least 4 seconds. The core may be repeatedly dipped or sprayed. The composition may comprise a core and a plurality of layers of coatings of additive. The layers of additive coating may be sequentially applied to the core. The composition may comprise a plurality of additive coating layers, wherein at least one additive coating layer has a different composition to the other additive coating layers. Dip coating enables the method to integrate easily into existing production lines. The weight of the additive coating on a core may be at least 1 g, preferably at least 2 g. The evaporation of the solvent may take place over a predetermined time period. For example, the solvent may be evaporated over a time period of at least 1 hour, preferably at least 2 hours. The solvent may be evaporated over a time period of no more than 24 hours, for example no more than 12 hours. The additive of the core is preferably sufficient such that the core is predominantly covered with the coating whilst providing an additive free portion of the core configured in ue for exposure to digestive fluids within the rumen. Preferably, the method requires no additional steps to coat the core with the additive coating. Preferably, the smectite incorporated alkyl cellulose-solvent mixture is applied to the core without requiring heating. As such, the additive may be applied to a core comprising heat sensitive additives without risk of degrading the additives during manufacture. The additive of the present invention is applied to the core, for example an animal feed pellet, and is configured to control release of active ingredients present within the core. The additive of the present invention when applied to the core is able to provide for controlled and consistent release of active ingredients present within the core. The additive of the present invention is biocompatible and non-toxic, and therefore can be used without producing any environmentally harmful byproducts. The additive is preferably composed entirely of components of natural origin. In use, the composition comprising the core and the additive of the present invention is preferably introduced into the rumen of an animal. The rumen juices (at a temperature of 37.5 °C to 40 °C) begin to breakdown an additive-free portion of the core. In one embodiment, an end of the core may be additive-free. For example, the core may be substantially cylindrical in shape and an end of the core may be additive-free. The additive begins to separate / break away from the core, thereby exposing further portions of the core for sustained release the required material (for example trace elements) into the rumen juices. According to a further aspect of the present invention, there is provided an apparatus for incorporating a core with a biocompatible, non-toxic additive, the apparatus comprising: a carrier for receiving and retaining at least one core; a reservoir comprising a smectite incorporated alkyl cellulose-solvent mixture as herein described; in which the reservoir is in fluid communication with the carrier to provide smectite incorporated alkyl cellulose-solvent mixture for incorporation with the or each core(s) mounted (for example retained) on the carrier. In one embodiment, the reservoir is in fluid communication with the carrier to provide smectite incorporated alkyl cellulose-solvent mixture for coating an outer surface of the core(s) mounted (for example retained) on the carrier. The reservoir may comprise a chamber configured to contain the smectite incorporated alkyl cellulose-solvent mixture, and at least one outlet in communication with the chamber. The outlet may for example be a spray nozzle configured to supply the smectite incorporated alkyl cellulose-solvent mixture to outer surfaces of the core(s) retained on the carrier. In one embodiment, the outlet(s) may be configured to receive the carrier and / or the core(s) therethrough for dipping into the smectite incorporated alkyl cellulose-solvent mixture. The one embodiment, the outlet is configured to supply the smectite incorporated alkyl cellulose-solvent mixture for mixing with the core(s) on the carrier. The apparatus may comprise a plurality of carriers enabling batchwise coating of a plurality of cores. According to a further aspect, the present invention provides the use of a composition comprising: a core comprising trace elements, and an additive as herein described for the treatment of diseases associated with trace element deficiency (such as for example selenium, cobalt, vitamin E or copper deficiency) in grazing animals, such as for example cattle, sheep, goats or deer. Trace element deficiency can lead to poor coat condition, lack of live weight and decreased fertility of the animal. Trace element deficiencies include for example parasitic gastroenteritis, pine, white muscle disease, nutritional muscular dystrophy, stiff lamb disease. According to a further aspect, the present invention provides the use of a composition comprising: a core, and an additive as herein described to reduce methane output in grazing animals, such as for example cattle, sheep, goats or deer. Embodiments of the present invention will now be described in more detail. BRIEF DESCRIPTION OF FIGURES Figure 1 is a photograph of a bolus with two coating layers of an additive according to one embodiment of the present invention; Figures 2A-C are photographs of the bolus of Figure 1 after 24 hours in a saline solution (Figure 2A) and after 2 weeks in a saline solution (Figures 2B-2C); Figures 3A-B are photographs of the coating of the additive according to one embodiment of the present invention (Figure 3A) and a conventional coating (vinyl resin); Figures 4A-D are photographs of boluses coated with an additive according to one embodiment of the present invention when exposed in ruminant fluid over time: Figure 4A (1 week); Figure 4B (2 week); Figure 4C (3 weeks); and Figure 4D (4 weeks). DETAILED DESCRIPTION Example 1 - Smectite Incorporated alkyl cellulose-solvent mixture A smectite incorporated alkyl cellulose-solvent mixture was prepared comprising: 10% to 90% w / w of at least one alkyl cellulose ether, in which the alkyl group of the alkyl cellulose is a C1-C10 alkyl group, and in which the at least one alkyl cellulose ether has a molecular weight in the range of between 75KDa and 400KDa; 10% to 90% w / w smectite; and a solvent-system comprising at least one Ci-Cio alkyl ester, and at least one C1-C5 alcohol, in which the ratio of the at least one Ci-Cio alkyl ester to the at least one C1-C5 alcohol is between 2:1 and 8:1. Example 2 - Method for producing a coated animal feed pellet An animal feed pellet was dipped twice into the bentonite incorporated ethyl cellulose-propanol mixture of Example 1. The mixture predominantly coated the outer surface of the animal feed pellet whilst leaving a coating-free portion for exposure to rumen digestive fluids once administered to an animal. The solvent was removed by evaporation to provide an additive coating comprising ethyl cellulose and bentonite. Example 3 - Solubility Test for coated animal feed pellet A bolus was coated with the bentonite incorporated ethyl cellulose-propanol mixture of Example 1 according to the method of Example 2. The bolus was repeatedly coated to comprise two layers of additive coating (as shown in Figure 1). It can be seen that the bolus has is substantially cylindrical in shape and has one end which is coating / additive free. The additive coated bolus is placed in saline solution and monitored over time. Figures 2A to 2C show that over time, the coating fragments and breaks away from the bolus when the underlying core dissolves in saline solution. The fragmentation of the coating exposes further sections of the bolus to the saline solution which will subsequently dissolve over time. After 24 hours (as shown in Figure 2A), an end of the coating adjacent the coating / additive free end of the bolus, begins to split, fragment and pull away from the underlying bolus. After 2 weeks (a shown in Figure 2B) bolus adjacent the coating / additive free end ha continued to dissolve resulting in larger sections of the coating to break away and fragment, exposing further sections of the bolus to the saline solution. The presence of the coating, which is sparingly soluble (or insoluble) in water, therefore controls exposure of the underlying bolus to external fluid such a rumen fluids, and therefore controls the release or degradation of the underlying bolus over time. The additive of the present invention, in the form of a coating, has been found to successfully provide for sustained release of ingredients within a bolus over a predetermined time period whilst having a substantially reduced thickness compared to conventional styrene-containing coatings. As shown in Figure 3A, the additive coating of the present invention has a thickness of 0.16 mm and provides for similar release properties as the conventional styrene containing coating shown in Figure 3B having a thickness of 0.34 mm. Therefore, the coating of the present invention provides for improved sustained release of ingredients within an underlying bolus whilst requiring the consumption of less materials during manufacture of the coated bolus. As shown in Figures 4A-D, the degradation of the 2-layer additive coated bolus of Figure 1 within rumen fluids was monitored over a four week period after administration to an animal. A first end of the substantially cylindrical bolus is free of additive coating. As shown in Figure 4A, the free end of the bolus begins to dissolve into the rumen fluids. However, the majority of the additive coating remains in tact surrounding the remaining portions of the bolus. As shown in Figure 4B, the free end of the bolus begins to dissolve into the rumen fluids and adjacent portions of the additive coating begin to detach and break away from the underlying bolus. The detachment of the additive coating over time exposes further portions of the underlying bolus to rumen fluids, providing for sustained, controlled release of ingredients within the bolus into the rumen fluids. Over time, as shown in Figures 4C and 4D, this process continues. Additive coating free portions of the bolus at or adjacent the end therefore continue to dissolve into the rumen fluids, thereby weakening the overlying coating layer, causing the additive coating to fragment, detach and break away from the bolus. Fragmentation and detachment of the additive coating thereby exposes still further portions of the bolus to the rumen fluids to provide further release of ingredients within the bolus.

Claims

1. A biocompatible, non-toxic additive for a core comprising:alkyl cellulose ether; andsmectite.

2. A biocompatible, non-toxic additive as claimed in claim 1, in which smectite comprises bentonite.

3. A biocompatible, non-toxic additive as claimed in either of claims 1 and 2, in which the alkyl cellulose ether has a molecular weight in the range of between 40,000 AMW to 1,300,000 AMW.

4. A biocompatible, non-toxic additive as claimed in any preceding claim, in which the alkyl group of the alkyl cellulose is a Ci-Cio alkyl group.

5. A biocompatible, non-toxic additive as claimed in any preceding claim, in which the alkyl group of the alkyl cellulose is a Ci-Cs alkyl group.

6. A biocompatible, non-toxic additive as claimed in any preceding claim, in which the alkyl group of the alkyl cellulose is selected from one or more of: methyl; ethyl; or any combination thereof.

7. A biocompatible, non-toxic additive as claimed in claim 6, in which the alkyl cellulose is ethyl cellulose.

8. A biocompatible, non-toxic additive as claimed in any preceding claim, in which the alkyl group of the alkyl cellulose is hydroxsubstituted.

9. A biocompatible, non-toxic additive as claimed in claim 8, in which the alkyl cellulose comprises one or more of: hydroxypropyl cellulose; hydroxypropylmethyl cellulose, or any combination thereof.

10. A biocompatible, non-toxic additive as claimed in claim 9, in which alkyl cellulose comprises hydroxypropyl cellulose.

11. A biocompatible, non-toxic additive as claimed in any preceding claim, in which alkyl cellulose comprises ethyl cellulose, and the smectite comprises bentonite12. A biocompatible, non-toxic additive as claimed in any preceding claim, in which alkyl cellulose is present within the coating in an amount of at least 10% w / w.

13. A biocompatible, non-toxic additive as claimed in any preceding claim, in which alkyl cellulose is present within the coating in an amount of no more than 90% w / w.

14. A biocompatible, non-toxic additive as claimed in any preceding claim, in which alkyl cellulose is present within the coating in an amount of between 30% and 70% w / w.

15. A biocompatible, non-toxic additive as claimed in any preceding claim, in which alkyl cellulose is present within the coating in an amount of approximately 60% w / w.

16. A biocompatible, non-toxic additive as claimed in any preceding claim, in which smectite is present within the coating in an amount of at least 10% w / w.

17. A biocompatible, non-toxic additive as claimed in any preceding claim, in which smectite is present within the coating in an amount of no more than 90% w / w.

18. A biocompatible, non-toxic additive as claimed in any preceding claim, in which smectite is present within the coating in an amount of approximately 40% w / w.

19. A biocompatible, non-toxic additive as claimed in any preceding claim, in which the coating is resin free.

20. A smectite incorporated alkyl cellulose-solvent mixture comprising:alkyl cellulose ether;smectite; anda solvent-system.

21. A smectite incorporated alkyl cellulose-solvent mixture as claimed in claim 20, in which the solvent-system comprises at least one alkyl ester and at least one alcohol.

22. A smectite incorporated alkyl cellulose-solvent mixture as claimed in claim 21, in which the at least one alkyl ester comprises at least one Ci-Cio alkyl ester, preferably at least one C2-C5 alkyl ester.

23. A smectite incorporated alkyl cellulose-solvent mixture as claimed in any one of claims 20 to 22, in which the alcohol comprises at least one C1-C5 alcohol, preferably propanol.

24. A smectite incorporated alkyl cellulose-solvent mixture as claimed in any one of claims 20 to 23, in which the ratio of the at least one alkyl ester to the at least one alcohol is at least 2:1.

25. A smectite incorporated alkyl cellulose-solvent mixture as claimed in any one of claims 20 to 24, in which the ratio of the at least one alkyl ester to the at least one alcohol is no more than 8:1.

26. A smectite incorporated alkyl cellulose-solvent mixture as claimed in any one of claims 20 to 25, in which the ratio of the at least one alkyl ester to the at least one alcohol is in the range of from 3:1 to 6:1.

27. A composition comprising: a core, and an additive as claimed in any one of claims 1 to 19 applied to or incorporated within the core.

28. A composition as claimed in claim 27, in which the core is predominantly coated with at least one coating layer of the additive.

29. A composition as claimed in claim 28, in which the at least one coating layer of the additive has a thickness of between 0.1 mm and 0.3 mm.

30. A composition as claimed in claim 29, in which the composition is an animal feed composition.

31. A method for the preparation of an additive as claimed in any one of claims 1 to 19, comprising:dissolving alkyl cellulose in a solvent-system to provide an alkyl cellulose-solvent mixture;introducing smectite into the alkyl cellulose-solvent mixture to provide a smectite incorporated alkyl cellulose-solvent mixture; andevaporating the solvent from the smectite incorporated alkyl cellulose-solvent mixture to provide a water soluble biodegradable coating.

32. A method as claimed in claim 31, in which the alkyl cellulose is dissolved in the solvent-system by high shear mixing.

33. A method as claimed in either of claims 31 and 32, in which the smectite is incorporated into the alkyl cellulose-solvent mixture under high shear.

34. A method for incorporating a biocompatible, non-toxic additive with a core (for example a pellet), the method comprising:dissolving alkyl cellulose in a solvent-system to provide an alkyl cellulose-solvent mixture;introducing smectite into the alkyl cellulose-solvent mixture to provide a smectite incorporated alkyl cellulose-solvent mixture;treating a core with the smectite incorporated alkyl cellulose-solvent mixture to provide a smectite-incorporated alkyl cellulose-solvent containing core; andevaporating solvent from the smectite-incorporated alkyl cellulose-solvent containing core to provide a core comprising a biocompatible, non-toxic additive.

35. A method as claimed in claim 34, in which the core is coated with the smectite incorporated alkyl cellulose-solvent mixture by dipping or spraying.

36. An apparatus for incorporating a core with a biocompatible, non-toxic additive, the apparatus comprising:a carrier for receiving at least one core;a reservoir comprising a smectite incorporated alkyl cellulose-solvent mixture as claimed in any one of claims 20 to 26;in which the reservoir is in fluid communication with the carrier to provide smectite incorporated alkyl cellulose-solvent mixture for incorporation with the or each core(s) mounted on the carrier.

37. Use of a composition comprising: a core comprising trace elements, and a biocompatible, non-toxic additive as claimed in any one of claims 1 to 19 for the treatment of diseases associated with trace element deficiency in grazing animals.

38. Use of a composition comprising: a core, and a biocompatible, non-toxic additive as claimed in any one of claims 1 to 19 to reduce methane output in grazing animals.

Images