GB2283677A

GB2283677A - Selenium containing anthelmintics based on avermectins and milbemycins

Info

Publication number: GB2283677A
Application number: GB9422588A
Authority: GB
Inventors: Colin Manson Harvey
Original assignee: Ashmont Holdings Ltd
Current assignee: Ashmont Holdings Ltd
Priority date: 1993-11-11
Filing date: 1994-11-09
Publication date: 1995-05-17
Anticipated expiration: 2014-11-09
Also published as: AU682064B2; AU7771794A; GB9422588D0; IE940879A1; NZ250188A; GB2283677B

Abstract

A stable liquid anthelmintic composition containing an active ingredient chosen from the groups of avermectins and milbemycins in combination with a liquid carrier and one or more selenium salts selected from the group of selenium salts which in the chosen liquid carrier do not break down the avermectins or milbemycins present in the composition. When the liquid carrier is a non-aqueous carrier, the selenium salt is chosen from the group comprising selenium oxides, selenium dioxide, selenium trioxide, and selenous acid. When the liquid carrier is an aqueous carrier, the selenium salt is chosen from the group comprising selenium edetate, ethylene diamino tetracetic acid selenium as a sodium salt, selenium amino acid chelates, selenium aminoates, selenium ascorbate, selenium aspartates and selenium proteinates. The composition allows for supplementation of selenium during routine drenching.

Description

FIELD This invention relates to an improved liquid anthelmintic selenium composition and a new method of producing selenized anthelmintic formulations for use as drenches, injectibles or pour-ons.

In particular this invention relates to anthelmintic drench formulations containing as at least one of the active ingredients one or more of the avermectins or milbemycins, and which further contains selenium.

BACKGROUND It is known that it is beneficial to include selenium in drenches in order to allow simple and effective supplementation of selenium with routine drenching.

Traditionally certain anthelmintic drenches have been selenized in New Zealand.

Selenium has been added using sodium selenate and sodium selenite, but these selenized drenches have been limited to those containing drench actives which are stable in the mixtures. These drench actives include benzimidazole and levamisole, but not the avermectins or milbemycins.

Until now it has not been possible to include the selenium additives in drenches containing avermectins or milbemycins as active ingredients. Stability studies have shown that the inorganic salts such as sodium selenate, when incorporated in anthelmintic drenches based on avermectins or milbemycins (such as ivermectin, moxidectin and doramectin), oxidise and break down the active compound. For example: oral ivermectin has a three month life with the addition of 20 mg/ml selenium and a 10 month life with 25 mg/ml selenium additives. Moxidectin oral shelf life after selenium addition is limited to six months.

OBJECT It is an object of this invention to provide a drench formulation which contains as at least one of the active ingredients one or more of the group of avermectins and milbemycins and which further contains selenium, or at least to provide the public with a useful choice.

STATEMENT OF INVENTION The anthelmintic drench formulations of this invention contain as at least one of the active ingredients one or more of the group of avermectins and milbemycins and further contain selenium in a selected form.

Preferably the selenium salt is an organic selenium such as selenium edetate; or an oxide chosen from the group comprising selenium trioxide, selenium dioxide or selenous acid (H2SeO3).

The drench formulations may further contain any of the other additives which are commonly found in drenches.

It has been surprisingly found that the addition of selenium in these forms provides a stable mixture in which avermectins and milbemycins can exist. Organic salts in aqueous solutions do not oxidise and break down the avermectins or milbemycins as was found in the case of sodium selenate or sodium selenite. (Alternatively selenium trioxide and dioxide in a non aqueous carrier can be used to provide a stable formulation.) In one aspect this invention provides an anthelmintic which contains as at least one of the active ingredients an anthelmintic from the groups of avermectins and milbemycins, and a selenium supplement in the form of one of the selected salts.

In another aspect this invention provides a method of simultaneously treating and providing a selenium supplement for non-human animals which comprises treating the animals with a formulation containing as at least one of the active ingredients an anthelmintic from the groups of avermectins and milbemycins, and a selenium supplement in the selected forms.

In a further aspect this invention provides a method of incorporating a selenium supplement into anthelmintics which contain as at least one of the active ingredients an anthelmintic from the groups comprising avermectins and milbemycins, by adding selenium to the anthelmintic composition in the form of an organic selenium salt, selenium dioxide, trioxide, or selenous acid.

In a preferred method of incorporating the selenium supplement in the case of anthelmintic drench the organic selenium salt would be ethylene diamino tetracetic acid selenium as a sodium salt with avermectins or milbemycins, other organic selenium salts are selenium amino acid chelates, selenium aminoates, selenium ascorbate, selenium aspartates and selenium proteinates.

In the case of injectibles or pour-ons in non-aqueous bases the preferred method is the incorporation of selenium dioxide or trioxide.

PREFERRED EMBODIMENTS Example 1 0.1% Moxidectin oral solution1 - to 100 ml Selenium edetate - 0.58 gms (1 - available as VETDECTIN (Trade Mark) oral solution from American Cyanamid).

Example 2 0.08% Ivermectin oral solution 2 - to 100 ml Selenium edetate - 0.46 gms (2 - available as IVOMEC (Trade Mark) oral solution from Merck Sharpe & Dohme.

Example 3 The formulations described in example 1 and example 2 were tested for stability by measuring the percentage active in the sample containing 0. 1% by weight of organic selenium (in the form of selenium edetate).

Percentage Active in Sample Ivennectin Solution Moxidectin Solution Start Date 0.078% 0. 11% + 2 months 0.078% 0.11% + 12months 0.078% 0.11% Additional stability trials are shown in Table 1 and Table 2. Table 1 shows a product stability trial on a formulation containing moxidectin + 0. 1% selenium and Table 2 shows a product stability trial of an ivermectin solution + 0.1% selenium.

TABLE 1

Physical Parameters Chemical Parameters Storage time and Appearance Appearance Density &commat; Viscosity &commat; pH Moxidectin Selenium temperature after inversion 20 C g/mL 20 C Ford &num; 4 g/L g/L Expected Level - - - - 0.99 1.00 Initial (07.04.94) Clear yellow OK 1.044 g/ml 16 seconds 6.4 0.96 g/l 0.92:0.95 liquid 3 months &commat; ambient Clear yellow, OK - some 1.037 g/ml 16 seconds 6.3 0.99 g/l 0.94 some sediment sediment 3 months &commat; 37 C Clear yellow, OK - some 1.037 g/ml 16 seconds 6.4 0.94 G.L 0.94 some sediment sediment TABLE 2

Physical Parameters Chemical Parameters Storage time and Appearance Appearance Density &commat; Viscosity &commat; pH Ivermeetin Selenium temperature after inversion 20 C g/mL 20 C Ford &num; 4 g/L g/L Expected Level - - - - 0.77 g/l 1.01 Initial (07.04.94) Clear pale OK 1.039 g/ml 10 seconds 6.6 0.74 g/l 0.96 yellow liquid 3 months &commat; ambient Clear yellow, OK - somme 1.033 11 seconds 6.3 0.80 g/l 0.97 some sediment sediment 3 months &commat; 37 C Clear yellow OK 1.033 Insufficient 6.4 0.80 G/L 0.94 sample Example 4 Another example would be that of a pour-on product.

Ivermectin 0.5% Selenium trioxide 0.71% Butyl dioxide to 100 Example 5 Or an injectible product.

Ivermectin 0.1% Glycerol formal 20% Selenium trioxide 0.71% Propylene glycol to 100 It will be appreciated that various alterations or modifications may be made to the foregoing without departing from the scope of this invention as claimed.

Claims

CLAIMS:

1. An anthelmintic composition comprising an active ingredient chosen from the groups of avermectins and milbemycins in combination with a liquid carrier and selenium salt selected from the group of selenium salts which in the chosen liquid carrier do not break down the avermectins or milbemycins present in the composition.

2. An anthelmintic composition as claimed in claim 1, wherein the selenium salt is chosen from the group comprising organic selenium salts, selenium oxides, selenium dioxide, selenium trioxide, and selenous acid.

3. An anthelmintic composition as claimed in claim 1, wherein the liquid carrier is an aqueous carrier and the selenium salt is chosen from the group comprising selenium edetate, ethylene amino tetracetic acid selenium as a sodium salt, selenium amino acid chelates, selenium aminoates, selenium ascorbate, selenium aspartates and selenium proteinates.

4. An anthelmintic composition as claimed in claim 1, wherein the liquid carrier is a non-aqueous carrier and the selenium salt is chosen from the group comprising selenium oxides, selenium dioxide, selenium trioxide, and selenous acid.

5. A method of simultaneously providing an anthelmintic and providing a selenium supplement for non-human animals which comprises treating the animals with a formulation containing as at least one of the active ingredients an anthelmintic chosen from the groups of avermectins and milbemycins, and a selenium salt chosen from the group comprising organic selenium salts, selenium oxides, selenium dioxide, selenium trioxide, and selenous acid.

6. A method as claimed in claim 5, wherein the organic selenium salt in the composition is selenium edetate.

7. A method of incorporating a selenium supplement into anthelmintic compositions which contain as at least one of the active ingredients an anthelmintic from the groups comprising avermectins and milbemycins, in combination with a liquid carrier, by adding selenium to the composition in the form of a selenium salt selected from the group of selenium salts which in the chosen liquid carrier do not break down the avermectins or milbemycins present in the composition.

8. A method as claimed in claim 6 wherein the selenium salt is chosen from the group comprising organic selenium salts, selenium oxides, selenium dioxide, selenium trioxide, and selenous acid.

9. An anthelmintic composition substantially as herein described with reference to any one of the examples.

10. A method of simultaneously drenching and providing a selenium supplement for non-human animals substantially as herein described with reference to any one of the examples.