AU2010210021B2 - The use of nickel in agriculture - Google Patents

Abstract

Abstract A method of maintaining or improving animal health, productivity and/or fertility by administering nickel to a non-human animal in a daily dose of about 0.001mg/kg/day to 1mg/kg/day by way of a trace element mineral supplement comprising nickel and a veterinary acceptable carrier, wherein the trace element mineral supplement does not contain starch or a protein source.

Description

AUSTRALIA Patents Act 1990 COMPLETE SPECIFICATION Standard Patent Applicant(s): OMNIA SPECIALITIES NZ LIMITED Invention Title: The use of nickel in agriculture The following statement is a full description of this invention, including the best method for performing it known to me/us: - 2 THE USE OF NICKEL IN AGRICULTURE FIELD OF INVENTION The present invention relates to the utilization of nickel in agriculture. 5 BACKGROUND Iron, cobalt, copper and zinc are all commonly recognised as important elements for plant and animal health. Nickel occurs in the periodic table flanked by Fe 10 & Co and Cu & Zn, however, nickel is never listed in trace element supplements for animals or plants. Copper, cobalt, selenium, iodine, zinc, manganese, chromium and boron always predominate in such recommendations. The Nickel Institute is a non profit organization 15 that represents the interests of 24 companies which together produce more than 90% of the world's annual nickel output. The Institute was established on January 1, 2004, through the merger of the Nickel Development Institute (NiDI) and the Nickel Producers Environmental 20 Research Association (NiPERA). The Nickel Institute has reviewed the direct and circumstantial evidence supporting the concept of essentiality of nickel in humans, animals, plants and microorganisms. As further data is developed to clarify 25 the essential role of nickel, a more quantitative requirement for this micronutrient will be developed. In plants and microorganisms nickel is known to function in several metalloenzymes including ureases, several hydrogenases and carbon monoxide dehydrogenase. 30 Nickel has been used to overcome a few specific plant ailments, including in Pecan, little leaf disorder and replant problems, little leaf of river birch and blister rust (Exobasidium vexans) on tea and cereals in Ceylon in 1959 (Plant Diseases and their Chemical control. E. Evans, 35 Blackwell Scientific Publications 1968). Horticulture and agriculture are becoming more - 3 intensive operations, particularly with dairy herds where up to several hundred animals may be involved. These require large inputs of nutrients to maintain productivity and high health. At the same time consumers are demanding 5 a more balanced approach and the organic movement is growing support. The organic approach cannot sustain intensive production, however there is room for middle ground where both approaches are accommodated. In horticulture this is referred to as integrated control 10 where chemical inputs are reduced and targeted for times of maximum effect. The produce is of high quality and residue free. The Apple Futures programme, run by PipFruit New Zealand, espouses this concept and aims to produce high quality, residue-free fruit. There is therefore a 15 need to provide new ways to address these issues in horticulture and agriculture. Although numerous detailed studies have been conducted with animals to determine the important role nickel plays in animal metabolism no products are sold 20 with nickel incorporated into trace element supplements. The present invention relates to the utilization of nickel in agriculture. OBJECT 25 It is an object of this invention to provide compositions, and methods to enhance the growth and/or health of animals. SUMMARY OF THE INVENTION 30 In a first broad aspect the invention provides a trace element mineral supplement for maintaining or improving animal health, productivity and/or fertility comprising nickel and a veterinary acceptable carrier, wherein the trace element mineral supplement does not 35 contain starch or a protein source. Thus, the present invention relates to the utilization of nickel in agriculture, in particular to facilitate animal health, disease control and growth, to enhance nutrient uptake and to increase nutrient values of animal tissues. Nickel provides beneficial effects to animals and plants directly, and also consequential health 5 benefits for consumers of plants treated with nickel. The invention provides a trace element mineral supplement for veterinary or agricultural use comprising nickel and a veterinary acceptable carrier for maintaining or improving animal health, productivity and/or fertility, wherein the 10 supplement does not contain starch or a protein source and is for administration of a daily dose of nickel of about 0.001mg/kg/day to 1mg/kg/day, to the animal. The daily dose of nickel is preferably from about 0.01mg/kg/day to 0.50mg/kg/day, more preferably from about 15 0.1mg/kg/day to 1mg/kg/day, and even more preferably about 0.15mg/kg/day to 0.40mg/kg/day. The daily dose of nickel can be achieved by: administration daily; slow release form to provide the daily dose; or an overdose that will make at least the 20 daily dose available to the animal, wherein the overdose is not toxic to the animal. The animals may be any animals, in particular farmed animals, for example, cattle, sheep, pigs, goats, poultry. The trace element mineral supplement may be 25 formulated as a drench, preferably a daily drench, a salt block, a food additive, such as an additive in a cereal feed etc., a water supply additive, an oral supplement or a composition for administration by injection. Preferably the supplement is formulated as a water supply additive. 30 In a preferred embodiment, the trace element mineral supplement comprises nickel in a dosage range of 1-500 mg of nickel, preferably 25-1000 mg of nickel, more preferably 50-1500 mg of nickel, even more preferably 100 150 mg of nickel. Preferably, the dosage form has a total 35 volume of 10ml. More preferably, the dosage form comprises 15mg/ml of nickel. More preferably, the unit dosage form comprises 2.3mg/l of nickel. Alternatively, - 5 the unit dosage form comprises 0.1-1mg of nickel (preferably in the form of nickel sulphate). The trace element mineral supplement according to the invention preferably includes one or more trace elements 5 selected from copper, zinc, manganese, cobalt, iodine, selenium, boron and chromium. In a preferred embodiment, the trace element mineral supplement comprises about 100mg nickel, 300mg zinc, 120mg copper, 2.4mg cobalt, 7.2mg iodine, 1.2mg selenium, 5mg boron, and 0.01mg chromium. 10 According to the invention, nickel may be used in any appropriate form in the compositions and methods disclosed herein, for example (but not limited to), nickel metal, nickel chloride (NiCl 2 ), nickel sulphide (NiS), nickel sulphate (NiSO 4 ), nickel oxide (NiO), nickel nitrate 15 (Ni(N0 3

)

2 , nickel subsulfide (Ni 3

S

2 ) and nickel lignosulfonate. Nickel is preferably applied as a salt, more preferably the salt is nickel sulphate although nickel chloride and other nickel salts may be used. The trace element mineral supplement according to the 20 invention includes a suitable carrier, preferably a carrier selected from molasses, glycerol and propylene glycol. In a preferred embodiment, the trace element mineral supplement according to the invention comprises 50g/l 25 nickel sulphate in 5% glycerol. This supplement is preferably provided to cattle at about 10ml (112mg) per cow/day, to sheep at about 5 ml (56mg) per sheep preferably once or twice a year. This supplement may also be administered as a daily dose to animals in drinking 30 water at 0.2ml/litre (2.2mg). In another preferred embodiment, the trace element mineral supplement according to the invention comprises 100g/l nickel sulphate in 5% glycerol. Preferably, the trace element mineral supplement of 35 the invention increases the fertility of the animal, increasing milk production of the animal and/or increases rumen efficiency of a ruminant animal, particularly the - 6 efficiency of one or more of the following enzymes: superoxide dismutase, urease, hydrogenase, methyl com reductase, co dehydrogenase and acetyl coA synthase. In a further embodiment, the invention provides a 5 method of maintaining or improving animal health, productivity and/or fertility by administering nickel to a non-human animal in a daily dose of about 0.001mg/kg/day to 1mg/kg/day by way of a trace element mineral supplement according to the invention. Preferably, fertility and/or 10 milk production is increased. The animal is preferably a farmed animal on a pasture-based diet. The animal is preferably selected from cattle, sheep, pigs, goats and poultry. In another embodiment, the invention provides a 15 method of synchronising estrous and/or ovulation in a group of animals by administering nickel to each animal in the group in a daily dose of about 0.01mg/kg/day to 1mg/kg/day by way of a trace element mineral supplement according to the invention. 20 In yet another embodiment, the invention provides a method of increasing rumen efficiency in a ruminant animal by administering nickel to a non-human animal in a daily dose of about 0.01mg/kg/day to 1mg/kg/day by way of a trace element mineral supplement according to the 25 invention. Preferably, the efficiency of one or more of the following enzymes is increased: superoxide dismutase, urease, hydrogenase, methyl com reductase, co dehydrogenase and acetyl coA synthase. Preferably, the animal is a cow, to which nickel is administered in a 30 daily dose of 0.2-500mg/day, preferably 0.2-200 mg/day, more preferably 0.2-150 mg/day. The invention also relates to the use of nickel for the manufacture of a composition for treating an animal according to a method of the invention. 35 BRIEF DESCRIPTION OF THE FIGURES Figure 1: shows the recommended daily dose rates of - 7 several trace elements to cows. The inventor considers the daily dose of nickel per cow is about 100-150mg/day. Figure 2: shows the condition of cows in March 2010 after a season of Nickel supplementation 5 DETAILED DESCRIPTION The inventor has recognised for the first time the key role played by nickel in many aspects of microbial, plant and animal metabolism. 10 The invention relates to compositions and methods for improving animal health by administering nickel to an animal. According to the invention, nickel may be used in any appropriate form in the compositions and methods disclosed herein, for example (but not limited to), nickel 15 metal, nickel chloride (NiCl 2 ), nickel sulphide (NiS), nickel oxide (NiO), nickel nitrate (Ni(N0 3

)

2 , nickel subsulfide (Ni 3

S

2 ) and nickel lignosulfonate. Nickel is preferably administered in the form of a salt. The salt is preferably nickel sulphate although nickel chloride and 20 other nickel salts may be used. It is believed that the application of nickel to animals improves metabolic processes in animals viz., protein synthesis, calcium, iron (red blood cells), copper, and molybdenum and vitamin B-12 metabolism, due to 25 the involvement of nickel in protein synthesis, calcium, iron, copper, molybdenum and vitamin B-12 metabolism. According to the invention, administration of nickel to ruminant animals increases rumen efficiency and reduces emission of methane. The inventor postulates that 30 increasing a ruminant's intake of nickel increases efficiency of microbial metabolism in the rumen. Within the rumen the following reactions are catalysed by nickel dependant enzymes; superoxide dismutase, urease, hydrogenase, methyl com reductase, co dehydrogenase and 35 acetyl coA synthase. Nickel supplementation could well affect the composition of milk due to altered up take and composition of rumen fatty acids.

- 8 Nickel may be applied alone or with fertilizer to elevate pasture or feed crop levels of nickel (as discussed in NZ Patent No. 578964 filed by the present inventor, which is incorporated herein by reference). The 5 treated pasture or feed crop also has higher nutritional value due to the ability of nickel to improve the uptake of nutrients, such as those selected from nitrogen, iron, manganese, calcium, potassium, phosphorous, sulphur, zinc, copper and nickel. Animal health benefits when animals 10 feed on the pasture or feed crop with elevated levels of nickel, and other nutrients. However, elevated levels of trace elements in pasture do not necessarily guarantee animals receive sufficient amounts. Therefore, daily dosing of animals with trace 15 element blends including; copper, zinc, manganese, cobalt, iodine, selenium, boron and chromium is common practice, especially in the dairy industry. The physiological importance of each element and the deficiency symptoms they invoke are well known and widely discussed in the 20 literature given to farmers. Nickel deficiency in animals evokes similar responses of ill thrift, depressed red cell blood levels and rough coat etc and this mineral should also be included in trace element blends. Uptake of nickel by animals by administration of a 25 composition comprising nickel or by ingesting treated feed, such as a crop or pasture, boosts animal health, in a similar manner to that touted for presently available mineral supplements which almost always comprise; copper, zinc, manganese, cobalt, iodine, selenium, boron and 30 chromium. For each of these elements several points of key physiological importance are claimed. For example, cobalt plays a key role in promoting bacterial growth in the rumen which is essential for vitamin B12 formation which facilitates the breakdown of propionic acid (a major 35 ruminant energy source). Cobalt also helps in the transport of folic acid to the liver. Deficiency symptoms of cobalt are ill thrift, lack of energy and poor -9 conception rates. Nickel plays a role in vitamin B12 metabolism as well as that of calcium, zinc, protein synthesis and red blood cell formation. As with other trace elements nickel 5 deficiency causes depressed growth, unthriftyness, rough hair coat, altered iron metabolism, depressed levels of calcium, zinc, haemoglobin and red blood cell counts and reduced survival of offspring. Nickel is an essential trace element for ruminant 10 health. Nickel can activate/inhibit crucial enzyme reactions, regulate protein synthesis, boost levels of haemoglobin and stimulate production of red blood cells. Nickel plays an interactive role in the functioning of metabolic systems like vitamin B-12. Nickel regulates 15 plasma levels of copper, zinc, molybdenum and iron, stimulates liver and kidney function; improves calcium uptake, zinc utilization and synthesis of homocysteine. Nickel also facilitates the survival of offspring. It is believed that the application of nickel to 20 animals increases red blood cell formation, increases calcium and zinc uptake, and increases protein synthesis, and thus muscle (meat) production, and increases survival rates of offspring. The potential impact of supplementing diets of 25 animals with nickel can be realised if one considers the insignificant role this important trace element is playing at present. As explained in NZ Patent No. 578964 filed by the present inventor naturally occurring levels of nickel in pasture are very low. For instance, a basal level of 30 say 0.08mg/kg of nickel in pasture means that fixation of urea-based fertilizers will be inefficient. The low levels of nickel in pasture are too low to impact on animal health. For example, a cow can consume approx 20kg DM/day which means that the daily intake of nickel by the 35 cow would be (20kg x 0.08mg/kg) = 1.6 mg Ni/day. If pasture had 5-10mg/kg of nickel (due to application of nickel according to NZ Patent No. 578964 filed by the - 10 present inventor), daily intake of nickel by the cow would be 100/200 mg per day respectively. The present invention relates to application of nickel at between 0.2-500mg to an animal such as a cow per day, preferably, 0.2-200 5 mg/day and more preferably 0.2-150mg/day. Trace elements are a particularly vital component in dairy cow nutrition. Inadequate levels can directly impact the cow; reducing milk production, decreasing fertility and causing metabolic disorders like lameness, bone 10 structure, rumen performance etc. During winter cows have a high trace element requirement due to late stages of pregnancy, low pasture intake, cool temperatures and high rainfall. Pre-calving, birthing and cycling are particularly demanding. Good management requires 15 implementation of intensive trace element supplementation before and during stress periods to avoid deficiencies. Animals may be dosed with nickel according to any means for supplementing animals with nutrients known in the art. Animals may be drenched with nickel by 20 application of nickel in their drinking water, or other direct oral application of formulation comprising nickel, such as with a drenching gun, by way of a pill or the like, or injected with a suitable formulation comprising nickel. Alternatively, or additionally, nickel may be 25 provided in mineral supplements in the form of salt blocks, in cereal feeds, in dry powder or pellet form etc. Nickel, for example in the form of dry pellet or powder, may be added to an animal's feed. The invention encompasses such trace element mineral supplements 30 comprising nickel. According to the invention any animals, particularly farmed animals such as cattle, sheep, pigs, goats and poultry, may be administered trace element mineral supplements comprising nickel according to the invention. 35 Animals are preferably administered with nickel at a dose of from about 0.001mg/kg/day to 1mg/kg/day, preferably about 0.01mg/kg/day to 0.50mg/kg/day, more - 11 preferably from about 0.01mg/kg/day to 1mg/kg/day, even more preferably about 0.15mg/kg/day to 0.40mg/kg/day, and more preferably about 0.29mg/kg/day to 0.33mg/kg/day. The daily dose of nickel can be achieved by: 5 administration daily; slow release form to provide the daily dose; or an overdose that will make at least the daily dose available to the animal, wherein the overdose is not toxic to the animal. Preferably, nickel is applied to cattle daily at a 10 dose of 0.2-500mg/day, 0.2-200mg/day, 0.2-150mg/day or 100-150mg/day. In a particular embodiment, nickel is administered to cows 3-4 weeks pre-calving and then daily for at least 100 days. The dose is preferably 10mls of a 15 mg/ml dose of 15 nickel (preferably in the form of nickel sulphate) daily following calving for 100 days. In another embodiment, nickel is administered to cows post-calving for the milking season. Each cow is preferably given 100-250mg of nickel per day. 20 In a particularly preferred embodiment, the invention relates to a dosage form comprising 100mg of nickel, preferably nickel sulphate, or other nickel salt. More preferably, the dosage form comprises 100mg nickel, 300mg zinc, 120mg copper, 2.4mg cobalt, 7.2mg iodine, 1.2mg 25 selenium, 5mg boron, and 0.01mg chromium. The composition of the invention may also be manufactured in larger amounts with the trace elements in these ratios for dispensing to animals. In a preferred embodiment, the trace element 30 supplement of the invention comprises nickel, preferably as nickel sulphate, and a carrier, optionally together with water. The carrier is preferably palatable to an animal, and may be, for example, molasses, propylene glycol or glycerol. In a preferred embodiment, the 35 carrier is glycerol. The trace element supplement can be prepared as a concentrate and subsequently diluted to provide nickel in the preferred dosages of the invention.

- 12 In another preferred embodiment, the trace element supplement of the invention comprises 25mg/ml of nickel, preferably as nickel sulphate in 25% glycerol. The preferred dosage rate of this formulation is 4-6ml/day to 5 deliver 100-150mg nickel per day to an animal such as a cow. However, trace element supplement may be administered to the animal at a dosage to provide between lmg-500mg of nickel per day. In a preferred embodiment, the trace element mineral 10 supplement according to the invention comprises 50g/l nickel sulphate in 5% glycerol. This supplement is preferably provided to cattle at about 10ml (112mg) per cow/day, to sheep at about 5 ml (56mg) per sheep preferably once or twice a year. This supplement may also 15 be administered as a daily dose to animals in drinking water at 0.2ml/litre (2.2mg). In another preferred embodiment, the trace element mineral supplement according to the invention comprises 100g/l nickel sulphate in 5% glycerol. 20 Several trace element supplements are currently available for animals, however, nickel is never listed as a supplement. Nickel is a contaminant in palm oil and other fatty acids that are used in some animal feeds, however, it has been seen to be a potentially toxic 25 contaminant rather than one for the benefit of animals. APAG, the European Oleochemicals and Allied Products Group, has undertaken to limit the amount of nickel in fatty acids for use in animal feed to 200ppm (0.02%). Odell et al (1970) "Nickel Toxicity in the Young 30 Bovine" J.Nutrition 100,1447-1454, fed 14 week old Holstein calves 0, 62.5, 250 and 1000ppm Ni (NiC03) for 8 wks. Growth was reduced slightly by 250ppm and greatly by 1000ppm. (Significant reduction weight projected at 300mg). The latter group lost weight but were not 35 emaciated and appeared younger suggesting a relationship between nickel and growth hormones. Internal organs were not affected, apart from kidneys at the highest dose.

- 13 The inventor considers that an optimum dose of nickel for animals per day is about 0.15mg/kg/day to 0.40mg/kg/day. The inventor believes that the optimum daily dose of 5 nickel for cows is about 100-150mg/day. A cow of about 350kg is preferably given 100mg/day of nickel, whereas a cow over 450kg is preferably given 150mg/day of nickel. Clearly, nickel is well tolerated by bovines and a daily dose rate of 100-150mg for mature cows would not be 10 excessive. The recommended daily dose rates for cows of several trace elements, zinc, manganese, copper, cobalt, iodine, selenium, boron and chromium are shown in figure 1. The inventor considers that the preferred daily dose of nickel 15 per cow is about 100-150mg/day, and this is also indicated in figure 1. The present invention relates to a trace element mineral supplement comprising nickel together with other trace elements, preferably in a dosage form comprising 20 100-150mg of nickel. Until the discovery of the role of nickel in jack bean urease (1975), no biological role for nickel was known. Urease is commonplace in bacteria and plants and catalyzes the hydrolysis of urea to release NH4*. 25 In 1975 the National Academy of Sciences published a monograph on nickel, ("Monograph on the evaluation of carcinogenic risks to humans", Vol 49, Nickel. Washington DC. National Academy of Sciences Publishing Office 1975) and concluded that the nickel ion (II) could either 30 activate or inhibit several enzymatic reactions of crucial importance in humans and animals. Evidence from animals on nickel deficient diets has shown organelle disruption, decreases in phospholipids, altered iron metabolism causing depressed hematopoiesis and thin, unthrifty 35 animals. Studies in goats, sheep and rats suggest a role for nickel in calcium, copper, zinc, molybdenum and vitamin B-12 metabolism.

- 14 Emerging evidence supports the concept of essentiality of nickel in humans, animals, plants and microorganisms. Given the prominence of nickel in the periodic table 5 and its location between cobalt and copper makes its absence in agriculture and horticulture practices to date seem all the more incredulous. However, nickel has been widely considered to be highly toxic, and this is possibly one reason why little attention has been paid to the use 10 of nickel in agriculture and horticulture. As used herein, where an amount of nickel sulphate (NiSO 4 ) is referred to by weight, it is meant the weight of nickel sulphate hexahydrate, ie, NiSO 4 .6H 2 0, unless otherwise stated. Where the amount of nickel is referred 15 to by weight, it is meant the weight of nickel as active ingredient. According to the invention, nickel may be used in any appropriate form in the compositions and methods disclosed herein, for example (but not limited to), nickel metal, 20 nickel chloride (NiCl 2 ), nickel sulphate (NiSO 4 ), nickel sulphide (NiS), nickel oxide (NiO), nickel nitrate (Ni(N0 3

)

2 , nickel subsulfide (Ni 3

S

2 ) and nickel lignosulfonate. Thus, where methods and compositions are described as including nickel sulphate, other forms of 25 nickel may be substituted. Example 1. Fowl feeding trial The water in a fowl house occupied by 4 fowls and 2 roosters was treated with nickel sulphate to give a level 30 of 125 mg/L on 1 April 2009. Three months later no ill effects were observed and fowl health was excellent. Example 2. Cattle feeding trial During the 2009-2010 milking season a trial was 35 conducted in Auroa, South Taranaki on a herd of 60 Holstein cows milked once a day, the herd having been milked for the last 30years.

- 15 The trial started in early October once the cows had calved and were in regular milking. Cows were fed a Nickel sulphate supplement daily mixed with molasses. Within ten days of Nickel sulphate supplementation significant 5 changes were observed in the cows. These are noted below; 1. The cows were keen to enter the shed and even young cows were pushing past older cows. 2. The Ni was well accepted by the animals 3. The cows were relaxed and easy to handle 10 4. Milk production increased by approximately 15% over the same time last year under essentially similar conditions 5. All of the cows cycled rapidly and came into season about the same time, even the older cows which can be 15 very difficult to get in calf. The Farmer has never seen this before. Many farmers inject B12 to help cows cycle. Nickel plays a part in regulating the synthesis of B12 and reproductive hormones. 6. All cows conceived on the first service 20 7. The motions of the cows were quite liquid which is typical of high performing animals 8. Food consumption of the animals did not increase 9. The trial started out feeding approx 200-250 mg of Ni per cow per day. Half way through the season the dose 25 was halved to around 100-120 mg of Ni per cow without any noticeable difference 10. When the Ni supplement was withdrawn for a few days the cows noticed immediately and became agitated until the Ni was resumed 30 11. The cows were still milking well and were in excellent condition when dried off in early March due to ill health of the farmer Figure 2 shows the condition of cows in March 2010 after a season of Nickel supplementation 35 Example 3. Cattle feeding trial - Milk production A herd of cows were fed nickel at a rate of - 16 10ml/cow/day during the milking season for a period of 17 days. Over the 17 day trial period, production of milk solids increased steadily from 3.7kgMS/ha/day to 3.95kgMS/ha/day. This is an increase of 6.8% over the 17 5 day trial. Example 4. trace element mineral supplement The following is an example of a trace element mineral supplement according to the invention. 10 Trace element mineral supplement example 1 BATCH SIZE 1000 Litres (Litres): RAW MATERIAL %w/v water 90.00 900.00 kg Nickel Sulphate 5.00 50.00 kg Glycerol 5.00 50.00 kg 100 1000 Manufacturing Instructions: 1. Add initial Load 3/4 water from meter to water tank. 2. Commence Commence stirring a moderate stirring speed. 3. Add Nickel Add Nickel crystals from bags Sulphate via top hatch. 4. Add Glycerol Add Glycerol via top hatch 5. Add final water Top up withfinal water 6. Continue Continue stirring overnight.

- 17 mixing 7. Take lab sample Take sample to lab for testing On lab approval, pack out via 20 8. Pack Out. micron filter to packaging S.G @ 20 0 C = 1.040 The trace element mineral supplement of example 4 is preferably provided to cattle at about 10ml (112mg) per cow/day, to sheep at about 5 ml (56mg) per sheep 5 preferably once or twice a year. The supplement can be administered for example by way of a drench gun. This supplement may also be administered as a daily dose to animals in drinking water, preferably at 0.2ml/litre (2.2mg). 10 The term "comprising" as used in this specification means "consisting at least in part of". When interpreting each statement in this specification that includes the term "comprising", features other than that or those prefaced by the term may also be present. Related terms 15 such as "comprise" and "comprises" are to be interpreted in the same manner. Wherein the foregoing description reference has been made to integers, features, elements or components having known equivalents then such equivalents are incorporated 20 as if individually set forth. Although the invention has been described by way of examples and with reference to possible embodiments, it is to be appreciated that improvements and/or modifications may be made to the illustrative embodiments without 25 departing from the scope or spirit of the invention. It is to be understood that, if any prior art publication is referred to herein, such reference does not constitute an admission that the publication forms a part of the common general knowledge in the art, in Australia - 18 or any other country.

Claims (68)

1. A method of maintaining or improving animal health, productivity and/or fertility by administering nickel to a 5 non-human animal in a daily dose of about 0.001mg/kg/day to 1mg/kg/day by way of a trace element mineral supplement comprising nickel and a veterinary acceptable carrier, wherein the trace element mineral supplement does not contain starch or a protein source. 10

2. A method according to claim 1 wherein the fertility of the animal is increased.

3. A method according to claim 1 wherein the 15 productivity of the animal is increased.

4. A method according to claim 3 wherein milk production of the animal is increased. 20

5. A method of synchronising estrous and/or ovulation in a group of non-human animals by administering nickel to each animal in the group in a daily dose of about 0.01mg/kg/day to 1mg/kg/day by way of a trace element mineral supplement comprising nickel and a veterinary 25 acceptable carrier, wherein the trace element mineral supplement does not contain starch or a protein source.

6. A method of increasing rumen efficiency in a ruminant animal by administering nickel to a non-human animal in a 30 daily dose of about 0.01mg/kg/day to 1mg/kg/day by way of a trace element mineral supplement comprising nickel and a veterinary acceptable carrier, wherein the trace element mineral supplement does not contain starch or a protein source. 35

7. A method according to claim 6 wherein the efficiency of one or more of the following enzymes is increased: - 20 superoxide dismutase, urease, hydrogenase, methyl com reductase, co dehydrogenase and acetyl coA synthase.

8. A method according to any one of claims 1-7 wherein 5 the daily dose of nickel is from about 0.01mg/kg/day to 0.50mg/kg/day.

9. A method according to any one of claims 1-7, wherein the daily dose of nickel is from about 0.1mg/kg/day to 10 1mg/kg/day.

10. A method according to any one of claims 1-7, wherein said daily dose of nickel is about 0.15mg/kg/day to 0.40mg/kg/day. 15

11. A method according to any one of claims 1-10 wherein the animal is a farmed animal on a pasture-based diet.

12. A method according to claim 11 wherein the animal is 20 selected from cattle, sheep, pigs, goats and poultry.

13. A method according to any one of claims 1-12 wherein the animal is a cow. 25

14. A method according to claim 13 wherein nickel is administered to the cow in a daily dose of 0.2-500mg/day.

15. A method according to claim 14 wherein nickel is administered to the cow in a daily dose of 0.2-200 mg/day. 30

16. A method according to claim 15 wherein nickel is administered to the cow in a daily dose of 0.2-150 mg/day.

17. A method according to any one of claims 1-16 wherein 35 the daily dose of nickel is achieved by: administration daily; slow release form to provide the daily dose; or an overdose that will make at least the daily dose available - 21 to the animal, wherein the overdose is not toxic to the animal.

18. A method according to any one of the preceding 5 claims, wherein said supplement is formulated as a drench, a salt block, a food additive, a water supply additive, an oral supplement or a composition for administration by injection. 10

19. A method according to claim 18 wherein said supplement is formulated as a water supply additive.

20. A method according to any one of claims 1-18 wherein the trace element mineral supplement comprises nickel in a 15 dosage range of 1-500 mg of nickel.

21. A method according to any one of claims 1-18 wherein the trace element mineral supplement comprises nickel in a dosage range of 25-1,000 mg of nickel. 20

22. A method according to any one of claims 1-18 wherein the trace element mineral supplement comprises nickel in a dosage range of 50-1500 mg of nickel. 25

23. A method according to any one of claims 1 to 22 wherein said supplement is formulated as a unit dosage form comprising 0.1 - 1 mg/kg/day of nickel.

24. A method according to claim 23, wherein the unit 30 dosage form has a total volume of 10ml.

25. A method according to any one of claims 1-18 wherein the unit dosage form comprises 2.2mg of nickel. 35

26. A method according to any one of claims 1-25, wherein the trace element mineral supplement includes one - 22 or more trace elements selected from copper, zinc, manganese, cobalt, iodine, selenium, boron and chromium.

27. A method according to claim 26, wherein the trace 5 element mineral supplement comprises about 100mg nickel, 300mg zinc, 120mg copper, 2.4mg cobalt, 7.2mg iodine, 1.2mg selenium, 5mg boron, and 0.01mg chromium.

28. A method according to any one of claims 1-27 wherein 10 the nickel is in the form of nickel metal, nickel chloride (NiCl2), nickel sulphide (NiS), nickel sulphate (NiSO4), nickel oxide (NiO), nickel nitrate (Ni(N03) 2 , nickel subsulfide (Ni 3 S 2 ) or nickel lignosulfonate. 15

29. A method according to any one of claims 1-28 wherein the nickel is in the form of nickel sulphate.

30. A method according to any one of claims 1-29, wherein the trace element mineral supplement includes a carrier 20 selected from molasses, glycerol and propylene glycol.

31. A method according to any one of claims 1-30 wherein the trace element mineral supplement comprises 50g/l nickel sulphate in 5% glycerol. 25

32. The use of nickel in the manufacture of a trace element mineral supplement for maintaining or improving animal health, productivity and/or fertility, wherein the trace element mineral supplement comprises nickel and a 30 veterinary acceptable carrier and is prepared for the administration of nickel to a non-human animal in a daily dose of about 0.001mg/kg/day to 1mg/kg/day, wherein the trace element mineral supplement does not contain starch or a protein source. 35

33. A use according to claim 32 wherein the fertility of the animal is increased. - 23

34. A use according to claim 32 wherein the productivity of the animal is increased. 5

35. A use according to claim 34 wherein milk production of the animal is increased.

36. The use of nickel in the manufacture of a trace element mineral supplement for synchronising estrous 10 and/or ovulation in a group of non-human animals, wherein the trace element mineral supplement comprises nickel and a veterinary acceptable carrier and is prepared for the administration of nickel to each animal in the group in a daily dose of about 0.01mg/kg/day to 1mg/kg/day, wherein 15 the trace element mineral supplement does not contain starch or a protein source.

37. The use of nickel in the manufacture of a trace element mineral supplement for increasing rumen efficiency 20 in a ruminant animal, wherein the trace element mineral supplement comprises nickel and a veterinary acceptable carrier and is prepared for the administration of nickel to a non-human animal in a daily dose of about 0.01mg/kg/day to 1mg/kg/day, wherein the trace element 25 mineral supplement does not contain starch or a protein source.

38. A use according to claim 37 wherein the efficiency of one or more of the following enzymes is increased: 30 superoxide dismutase, urease, hydrogenase, methyl com reductase, co dehydrogenase and acetyl coA synthase.

39. A use according to any one of claims 32-38 wherein the daily dose of nickel is from about 0.01mg/kg/day to 35 0.50mg/kg/day. - 24

40. A use according to any one of claims 32-38, wherein the daily dose of nickel is from about 0.1mg/kg/day to 1mg/kg/day. 5

41. A use according to any one of claims 32-38, wherein said daily dose of nickel is about 0.15mg/kg/day to 0.40mg/kg/day.

42. A use according to any one of claims 32-41 wherein 10 the animal is a farmed animal on a pasture-based diet.

43. A use according to claim 42 wherein the animal is selected from cattle, sheep, pigs, goats and poultry. 15

44. A use according to any one of claims 32-43 wherein the animal is a cow.

45. A use according to claim 44 wherein said daily dose of nickel is 0.2-500 mg/day. 20

46. A use according to claim 45 wherein said daily dose of nickel is 0.2-200 mg/day.

47. A use according to claim 46 wherein said daily dose 25 of nickel is 0.2-150 mg/day.

48. A use according to any one of claims 32-47 wherein the supplement is prepared to achieve the daily dose of nickel by: administration daily; slow release form to 30 provide the daily dose; or an overdose that will make at least the daily dose available to the animal, wherein the overdose is not toxic to the animal.

49. A use according to any one of claims 32-48, wherein 35 said supplement is formulated as a drench, a salt block, a food additive, a water supply additive, an oral supplement or a composition for administration by injection. - 25

50. A use according to claim 49 wherein said supplement is formulated as a water supply additive. 5

51. A use according to any one of claims 32-49 wherein the trace element mineral supplement comprises nickel in a dosage range of 1-500 mg of nickel.

52. A use according to any one of claims 32-49 wherein 10 the trace element mineral supplement comprises nickel in a dosage range of 25-1,000 mg of nickel.

53. A use according to any one of claims 32-49 wherein the trace element mineral supplement comprises nickel in a 15 dosage range of 50-1500 mg of nickel.

54. A use according to any one of claims 32-53 wherein said supplement is formulated as a unit dosage form comprising 0.1-1 mg/kg/day of nickel. 20

55. A use according to claim 54, wherein the unit dosage form has a total volume of 10ml.

56. A use according to any one of claims 32-49 wherein 25 the unit dosage form comprises 2.2mg of nickel.

57. A use according to any one of claims 32-56, wherein the trace element mineral supplement includes one or more trace elements selected from copper, zinc, manganese, 30 cobalt, iodine, selenium, boron and chromium.

58. A use according to claim 57, wherein the trace element mineral supplement comprises about 100mg nickel, 300mg zinc, 120mg copper, 2.4mg cobalt, 7.2mg iodine, 35 1.2mg selenium, 5mg boron, and 0.01mg chromium. - 26

59. A use according to any one of claims 32-58 wherein the nickel is in the form of nickel metal, nickel chloride (NiCl 2 ), nickel sulphide (NiS), nickel sulphate (NiSO 4 ), nickel oxide (NiO), nickel nitrate (Ni(N0 3 ) 2 , nickel 5 subsulfide (Ni 3 S 2 ) or nickel lignosulfonate.

60. A use according to any one of claims 32-59 wherein the nickel is in the form of nickel sulphate. 10

61. A use according to any one of claims 32-60, wherein the trace element mineral supplement includes a carrier selected from molasses, glycerol and propylene glycol.

62. A use according to any one of claims 32-61 wherein 15 the trace element mineral supplement comprises 50g/l nickel sulphate in 5% glycerol.

63. A method according to claim 1 substantially as herein described or exemplified. 20

64. A method according to claim 5 substantially as herein described or exemplified.

65. A method according to claim 6 substantially as herein 25 described or exemplified.

66. A use according to claim 32 substantially as herein described or exemplified. 30

67. A use according to claim 36 substantially as herein described or exemplified.

68. A use according to claim 37 substantially as herein described or exemplified.