# Patent

## Title
Trace elements

## Abstract

The inventions discloses a trace element solution, which comprises at least the following metals: zinc; manganese; selenium; and copper; and which comprises a concentration of the metals of at least 90 mg/ml. The solution may comprise the following concentrations: at least 60 mg/ml zinc; at least 10 mg/ml manganese; at least 5 mg/ml selenium; and at least 15 mg/ml copper. The solution may comprise chromium, iodine and chromium.

## Background
FIELD OF INVENTION
The present invention relates to trace elements.
BACKGROUND TO INVENTION
It has been found that there is a deficiency of certain trace elements in pastures for livestock in particular areas around the world. Various suggestions have been made to provide the required trace elements to such animals. Different chemical compounds and complexes have been investigated for applying the trace elements by way of licks, drenches or injections.
In general the problem with injectable solutions is that the concentrations of the minerals in the solutions is too low. This means that relatively large quantities have to be injected, which in turn causes tissue damage and also abscesses at the site of injection. Furthermore, it is generally the case that different trace elements seldomly are individually sufficient. This means that two or more trace element solutions have to be provided by way of separate injections.
ZA 1982/6778 (Laurie) discloses a trace element solution and a method of providing the trace elements to livestock. These trace element solution include ethylene diamino tetra acetic acid complex of the required mineral in suitable quantities. However, the trace element solution includes no selenium or selenite compound.
In the specification and claims the expression EDTA refers to ethylene diaminotetraacetic acid (C10H16O8N2 or (HO2CH2C)2NCH2CH2N—(CH2CO2H)2).
U.S. Pat. No. 4,335,116 (Howard) discloses mineral-containing therapeutic compositions containing EDTA complexes of trace elements. Notably, U.S. Pat. No. 4,335,116 utilises tetra-sodium EDTA, a selenium glycine complex, and metal chlorides for the preparation of the EDTA complexes. Unfortunately, the chloride ions cause contamination and each complex solution is to be made individually. Furthermore, overnight time is required for complexing and heating up afterward to speed up the process, requires extra apparatus. If mixtures are required, the individual solutions are to be blended. If various concentrations as well as compositions are to be made, it can only be done in a cumbersome way, requiring extra apparatus. A further problem arises when mixtures of high concentration are needed. In certain cases it would be impossible to deliver them, because mixing is always accompanied by dilution. The maximum concentration achieved with this method was 13.5 mg/ml.
U.S. Pat. No. 6,638,539 (Laurie et al) discloses a method of preparing a trace element solution, which includes the steps of providing at least one EDTA-complex, of providing a sodium selenite solution, and of combining the EDTA-complexes and the sodium selenite solution. However, the method enables production of a trace element solution of only about 55 mg/ml.
U.S. Pat. No. 7,285,292 (Laurie et al) discloses a trace element solution, which comprises at least one metal selected from the group comprising selenium, copper, zinc, manganese and chromium and which comprises a concentration of the metal(s) of at least 60 mg/ml. The solution further comprises at least one compound selected from the group comprising iodine, potassium iodide, sodium iodide, iron, iron chloride, zinc oxide, manganese sulphate, sodium selenite, copper carbonate, sodium carbonate, anhydrous disodium EDTA and sodium hydroxide. The trace element solution is prepared by a method consisting essentially of the steps of preparing a MnCO3 mixture in a container; adding an EDTA/NaOH mixture to the container and subsequently adding at least one metal compound; and adding Na2SeO3 to the container to obtain the trace element solution. The method also comprises the step of adding CrCl3.6H2O to the trace element solution.
Unfortunately the known solutions and methods therefore cannot provide solutions with suitable composition with high enough concentrations and sufficient ratios and sufficient concentrations of the various metals.
It is an object of the invention to suggest methods and means for overcoming these problems.
SUMMARY OF INVENTION
According to the invention, a trace element solution, which comprises at least the following metals:

    
    
        (a) zinc;
        (b) manganese;
        (c) selenium; and
        (d) copper;

and which comprises a concentration of the metals of at least 90 mg/ml.

    
    


Also according to the invention, a method of preparing a trace element solution comprising at least one metal selected from the group comprising zinc, manganese, selenium, and copper and comprising a concentration of the metals of at least 90 mg/ml, said method consisting essentially of the steps of:

    
    
        (a) heating water;
        (b) adding manganese carbonate to the water;
        (c) adding zinc oxide to the water; and
        (d) adding copper carbonate to the water to form a liquid mixture;
        (e) adding a dry mixture comprising EDTA and/or EDDS and NaOH to the liquid mixture; and
        (f) adding Na2SeO3 to form the trace element solution.
    
    


Yet further according to the invention, a trace element solution as prepared by the method as described herein.
Yet further according to the invention, a method of providing trace elements to animals, such as livestock, which comprises the steps of preparing a trace element solution as described herein and of providing the solution in a suitable quantity to an animal.
The method of preparing a trace element solution may be a continuous batch process.
The solution may comprise the following concentrations:

    
    
        (a) at least 60 mg/ml zinc;
        (b) at least 10 mg/ml manganese;
        (c) at least 5 mg/ml selenium; and
        (d) at least 15 mg/ml copper.
    
    


The solution may comprise chromium.
The solution may comprise iodine.
The solution may comprise at least 5 mg/ml chromium.
The solution may comprise at least 50-300 mg/ml iodine.
The ratio of zinc to manganese may be at least 2:1
The ratio of zinc to manganese may be at least 4:1
The ratio of zinc to copper may be at least 2:1 or 4:1
The ratio of zinc to selenium may be at least 4:1 or 12:1
The solution may comprise at least one compound selected from the group comprising chromium, iron, iodine, potassium iodide, sodium iodide, iron chloride, zinc oxide, manganese sulphate, manganese carbonate, sodium selenate, sodium selenite, copper carbonate, sodium carbonate, anhydrous disodium EDTA and sodium hydroxide.
At least one of the metal(s) may be provided in the form of an EDTA complex and/or an EDDS complex.
The EDTA source may be EDTA acid, disodium EDTA, tetra-sodium EDTA, calcium EDTA, potassium EDTA and/or any other EDTA source.
The solution may comprise chloro-cresol and/or benzyl alcohol as preservative.
The solution may be an injectable solution.
The solution may be a drenchable solution.
Step (a) may heat the water to 70 degrees Celcius.
The adding in step (e) may occur slowly to prevent excessive frothing.
The solution may be a clear blue solution.
The temperature of the solution may reach 100 degrees Celcius.
The solution may be allowed to cool.
The solution may after cooling have a temperature of 50 degrees Celcius.
Chloro-cresol may be added to the solution and stirred until dissolved.
The pH of the solution may be adjusted.
Water may be added to the solution.
The method may comprise the step of adding CrCl3.6H2O to the trace element solution.
The method may comprise the step of adjusting the pH of the trace element solution to 6.0 to 8.0
The method may comprise the step of adjusting the pH of the trace element solution by adding at least one compound selected from the group comprising NaOH and EDTA.
The trace element solution may be diluted.
The temperature of the MnCO3 mixture may be at least 60 degrees Celsius.
Water having a temperature of at least 70 degrees Celsius may be added to the MnCO3 mixture.
The addition of the EDTA/NaOH mixture may occur gradually with small quantities.
The method may comprise the step of cooling the trace element solution prior to addition of the Na2SeO3.
The MnCO3 mixture may be obtained directly and/or prepared by mixing MnSO4 and Na2CO3.
The metal compound may be selected from the group comprising ZnO, CuCO3, Na2CO3, MnSO4 and FeCl3.
The metal compound may be selected from the group comprising metal oxides, metal hydroxides and metal carbonates.


DESCRIPTION OF EXAMPLE
The invention will now be described by way of an example of injectable solutions in accordance with the invention.
The example relates to a method to prepare a trace element solution predominantly to be used for cattle and includes the mineral elements zinc, manganese, selenium and copper.
The method enables preparation of 25 liters of the solution containing at least 60 mg Zn, 10 mg Mn, 5 mg Se, and 15 mg Cu per ml.
In a 25 liter plastic container, water is heated to a temperature of 70 degrees Celsius so that the process can proceed at a temperature of at least 60 degrees Celsius.
0.556 Kilogram of manganese carbonate is added to the heated water whilst mixing.
1.890 Kilogram of zinc oxide is added to the mixture.
0.700 Kilogram of copper carbonate is added to the mixture slowly to form a liquid mixture.
In a separate container 10.17 kilogram EDTA and 2.70 kilogram of NaOH are mixed to form a dry mixture.
The dry mixture is slowly added to the liquid mixture to prevent excessive frothing and allow the reaction to complete and to leave a clear blue solution.
The temperature of the solution may reach 100 degrees Celsius and is allowed to cool to 50 degrees Celsius.
26.25 g of Chloro-cresol is added to the solution and is stirred until dissolved.
The solution is then cooled to room temperature.
The recorded pH of the solution is now 4.656.
0.303 Kilogram of Na2SeO3 is added.
The recorded pH of the solution is now 5.115.
The pH is adjusted to 6.860 by adding a 50% NaOH solution.
The solution is now diluted with water to obtain the required weight, namely 1.300 kg/l.
The resultant trace element solution has a composition as follows:

    
    
        (a) 60 mg/ml of zinc;
        (b) 10 mg/ml manganese;
        (c) 5 mg/ml selenium; and
        (d) 15 mg/ml copper.
    
    


The invention therefore provides a trace element solution which is tissue friendly, i.e. is not damaging or irritant to the tissue of animals and which comprises zinc, manganese, selenium and copper and at a concentration of the metals of at least 90 mg/ml.
The trace elements in solution are in a scientifically formulated ratio according to the post-absorption requirements of the animals.
As an example the trace element solution comprises

    
    
        (a) at least 60 mg/ml of zinc;
        (b) at least 10 mg/ml manganese;
        (c) at least 5 mg/ml selenium; and
        (d) at least 15 mg/ml copper.
    
    


The solution may furthermore comprise at least 5 mg/ml chromium and at least 50-300 mg/ml iodine.
The method of preparing a trace element solution in accordance with the invention thus enables the production of a solution comprising an adequate trace mineral concentration so that a 5 to 10 milliliter injection can make a significant impact on the trace mineral status of the animal and an injection is provided at a rate of between 1 ml per 50 kg bodyweight (BW) and 1 ml per 100 kg BW, i.e. a practically applicable injectable supplement and a product that can improve the trace mineral status of an animal is provided. This is important as livestock producers will only inject livestock if a real benefit can be demonstrated. The subcutaneous injection is the preferred route to minimize tissue damage, but intra-muscular injection can also be used.

## Claims

1. A method of preparing a trace element solution with a concentration of the metals of at least 90 mg/ml, said method comprising:
(a) heating water;
(b) adding manganese carbonate to the water wherein manganese sulphate and sodium carbonate are not used in situ manufacture of the manganese carbonate;
(c) adding zinc oxide to the water;
(d) adding copper carbonate to the water to form a liquid mixture;
(e) adding a dry mixture comprising ethylene diaminotetraacetic acid (EDTA) and/or ethylenediamine-N,N′-disuccinic acid (EDDS) and NaOH to the liquid mixture; and
(f) adding Na2SeO3 to form the trace element solution with a concentration of metals of at least 90 mg/ml,
wherein the trace element solution has at least 60 mg/ml zinc.

2. The method as claimed in claim 1, in which in step (a) the water is heated to 70° C.

3. The method as claimed in claim 1, in which step (e) occurs slowly to prevent excessive frothing.

4. The method as claimed in claim 1, further comprising adding chloro-cresol to the solution and stirred until dissolved.

5. The method as claimed in claim 1, in which the pH of the solution is adjusted.

6. The method as claimed in claim 1, further comprises adding CrCl3.6H2O to the trace element solution.

7. The method as claimed in claim 1, further comprises adjusting the pH of the trace element solution to 6.0 to 8.0.

8. The method as claimed in claim 1, further comprises adjusting the pH of the trace element solution by adding at least one compound selected from the group consisting of NaOH and EDTA.

9. The method as claimed in claim 1 further comprises cooling the trace element solution prior to addition of the Na2SeO3.

10. The method as claimed in claim 1, which is a batch process.

11. A trace element solution which is prepared by the method as claimed in claim 1.

12. A method of preparing a trace element solution with a concentration of metals being at least 90 mg/ml, said method consisting essentially of the steps of:
(a) heating water;
(b) adding manganese carbonate to the water wherein manganese sulphate and sodium carbonate are not used in situ manufacture of the manganese carbonate;
(c) adding zinc oxide to the water;
(d) adding copper carbonate to the water to form a liquid mixture;
(e) adding a dry mixture comprising ethylene diaminotetraacetic acid (EDTA) and/or ethylenediamine-N,N′-disuccinic acid (EDDS) and NaOH to the liquid mixture; and
(f) adding Na2SeO3 to form the trace element solution having at least 90 mg/ml of metals,
wherein the trace element solution has at least 60 mg/ml zinc.

13. The trace elements solution of claim 11, wherein the metals have the following concentrations:
(a) at least 10 mg/ml manganese;
(b) at least 5 mg/ml selenium; and
(c) at least 15 mg/ml copper.

14. The trace elements solution of as claimed in claim 11, in which the ratio of zinc to manganese is at least 2:1.

15. The trace elements solution of claim 11, in which the ratio of zinc to manganese is at least 4:1.

16. The trace elements solution of claim 11, in which the ratio of zinc to copper is at least 2:1 or 4:1.

17. The trace elements solution of claim 11, in which the ratio of zinc to selenium is at least 4:1 or 12:1.

18. The trace elements solution of claim 11, in which at least one of the metals is provided in the form of an ethylene diaminotetraacetic acid (EDTA) complex and/or an ethylenediamine-N,N′-disuccinic acid (EDDS) complex.

19. The trace elements solution of claim 17, in which the EDTA source is EDTA acid, disodium EDTA, tetra-sodium EDTA, calcium EDTA, potassium EDTA and/or any other EDTA source.

20. A trace element solution with a concentration of the metals of at least 90 mg/ml, produced by the method of claim 12.

21. The trace elements solution of claim 20, wherein the metals have the following concentrations:
(a) at least 10 mg/ml manganese;
(b) at least 5 mg/ml selenium; and
(c) at least 15 mg/ml copper.

22. The trace elements solution of claim 20, in which the ratio of zinc to manganese is at least 2:1.

23. The trace elements solution of claim 20, in which the ratio of zinc to manganese is at least 4:1.

24. The trace elements solution of claim 20, in which the ratio of zinc to copper is at least 2:1 or 4:1.

25. The trace elements solution of claim 20, in which the ratio of zinc to selenium is at least 4:1 or 12:1.

26. The trace elements solution of claim 20, in which at least one of the metals is provided in the form of an ethylene diaminotetraacetic acid (EDTA) complex and/or an ethylenediamine-N,N′-disuccinic acid (EDDS) complex.

27. The trace elements solution of claim 26, in which the EDTA source is EDTA acid, disodium EDTA, tetra-sodium EDTA, calcium EDTA, potassium EDTA and/or any other EDTA source.