NZ336832A - Anthelmintic formulation comprising praziquantel, a macrolide, a preservative, buffer salts, defoaming agent, dispersing agent and water - Google Patents

Abstract

This anthelminitic composition comprises: a) at least on macrolide; b) Praziquantel; c) a wetting agent; d) a preservative; e) buffer salts; f) a defoming agent g) a dispersing agent; and h) water.

Description

Patents Form # 5 NEW ZEALAND Patents Act 1953 COMPLETE SPECIFICATION AFTER PROVISIONAL #: 336832 DATED : 21 July 1999 TITLE: Anthelmintic Formulation We, Ancare New Zealand Limited Address: 48 Diana Drive, Glenfield, Auckland, New Zealand Nationality: A New Zealand company do hereby declare the invention for which we pray that a patent may be granted to us and the method by which it is to be performed, to be particularly described in and by the following statement: , i uml fHUHIiHTV OF'Oc OF N.Z PF05.JWP FEE CODE 1050 2 0 jul 2000 received.

FIELD OF THE INVENTION This invention relates to formulations containing a combination of the anthelmintics. BACKGROUND Praziquantel and macrolides have different parasite specificities. In general macrolides are 5 effective in the elimination of a broad spectrum of internal and external parasites of cattle, sheep and other farm animals. However they are substantially ineffective against the trematodes and in particular tapeworms.

There are a number of trematodes which are important parasites of cultivated farm species. These include by way of example Monezia spp and the horse tapeworm Anacephlea.

Praziquantel by comparison is effective against tapeworms. However it is difficult to formulate a liquid composition of praziquantel.

It is therefore desirable to treat animals with a combination of at least one macrolide and praziquantel to obtain maximum benefit of treatment.

Obviously it is possible to administer the two independently but within a limited time of 15 each other. However this is costly and time consuming. The time involved in double dosing all of a herd of cattle or a flock of sheep is considerable.

It is therefore desirable to formulate a composition which is capable of maintaining both macrolides and praziquantel in bioavailable states in a stable formulation.

For the purposes of this specification "stable veterinary liquid anthelmintic composition 20 suitable for administration to warm-blooded animals" means: A liquid composition having the required shelf life enabling it to be sold as an animal remedy or veterinary medicine. Such a composition should also be capable of being stored at ambient temperatures; it should travel well; and should be easily mass-administered to farm animals throughout its shelf life. This term includes liquids which van be delivered as an injection, or as a pour on, 25 or as an oral drench. Registration in accordance with the Animal Remedies Act 1967 (or .,,,-^u.viUHL KHUPERTV OF^'oif OF N.Z 2 0 ju l 2000 received T8417CS1,500/EB/nk equivalent legislation) typically requires such a composition to exhibit a shelf life of one to two years preferably at least 2 years.

OBJECT It is an object of this invention to provide a composition which stably contains both 5 praziquantel and at least one macrolide, or one which at least provides the public with a useful choice.

STATEMENT OF THE INVENTION In one aspect the invention relates to a composition suitable, for administration to warmblooded non-human animals comprising an effective amount of at least one macrolide and 10 an effective amount of praziquantel in suspension, together with a wetting agent, a preservative, buffer salts, a defoaming agent, a dispersing agent and water to volume.

Preferably the macrolide is present in the range 0.05 to 0.5% w/v.

Preferably the macrolide is selected from the group comprising the avermectins and the milbemycins.

More preferably the macrolide is selected from moxidectin, ivermectin, abamectin, and doramectin.

Preferably the praziquantel is present in the range from 1-5% w/v.

Preferably the wetting agent is present in the range of 1-30% w/v.

Preferably the wetting agent is selected from the group polyoxyethylated vegetable oils, 20 polyoxyethylene sorbitan monoisostearate, and polyoxyethylene (20) sorbitan monooleate.

Preferably the wetting agent is polyoxyethylene (20) sorbitan monooleate.

Preferably the preservative is present in the range 0-5% w/v.

Preferably the preservative is selected from the group benzyl alcohol, methyl paraben and formalin. —l khupertv QFc;cjf OF N.Z 2 0 jul 2000 _received T84 ] 7CS1,500/EB/nk More preferably the preservative is benzyl alcohol.

Preferably the defoaming agent is present in the range from 0.5-2% w/v.

Preferably the defoaming agent is silicon dioxide or defoaming agent RD.

More preferably the defoaming agent is silicon dioxide.

Preferably the dispersing agent is present in the range from 0-1% w/v.

Preferably the dispersing agent is selected from the group comprising PEG 6000 and other PEG compounds.

More preferably the dispersing agent is PEG 6000.

In addition the composition may include buffering agents, thickeners and other adjuvants 10 whish assist in the final formulation. In addition the composition may include mineral and elements which assist in the action of the actives.

PREFERRED EMBODIMENT These and other aspects of this invention, which should be considered in all its novel aspects will be apparent from the following example.

It has been surprisingly found that it is possible to devise a formulation which satisfies the requirements of both macrolides and praziquantel.

Example Raw Material: % w/v Water PEG 40 Stearate PEG 6000 Defoamer RD T8417CS1.500/EB/nk 52.00 3.50 4.00 0.20 ,^w.u*L rHUWBfl-v OF-CE OF N.Z 2 0 jul 2000 received Praziquantel 3.75 Aerosil 200 0.50 MPG 0.40 Xanthan Gum 0.20 Water 5.0 Sodium dihydrogen phosphate 0.5 (NaH2P04.2H20) Disodium hydrogen phosphate 0.5 (Na2HP04.2H20) Selenium chelate 0.25 chelated minerals - NZ mix 10.00 Abamectin 0.10 Benzyl alcohol 2.00 Polysorbate 80 3.00 Water To volume lOO.OOmL Manufacturing Instructions: 1. In a clean, dry mixing vessel, stir and heat to dissolve the first water aliquot, the PEG 40 stearate and the PEG 6000. 2. Stir in the Defoamer RD. 3. Silverson in the praziquantel. 4. Silverson in the Aerosil 200.

. Premix the MPG and the xanthan gum and silverson this into the batch until it is smooth and lump free. fhupertv ofpce" OF N.Z jul 2000 received T8417CS1.500/EB/nk 6. In another clean, dry, mixing vessel, stir and heat if necessary to dissolve each one before the next is added; the second water aliquot, the sodium dihydrogen phosphate, the disodium hydrogen phosphate, the selenium chelate and the chelated minerals - NZ mix. 7. In another clean dry mixing vessel, heat and stir to dissolve the abamectin in the benzyl alcohol. 8. Stir in the polysorbate 80. 9. To the praziquantel phase, add the mineral phase and mix well.

. Then silverson in the abamectin phase. 11. Make up to volume with water and mix well. 12. Package the product.

Example 2 Raw Material: % w/v Moxidectin 0.5- 0.05 Tween 80 5-30 Benzyl Alcohol 0-2% Sodium Phosphate Dibasic Less than 0.5 Sodium Phosphate Monobasic Less than 1 Praziquantel 1-5 PEG 6000 2-5 Silicon dioxide 0.5-2 Water To volume I UML rKUPERTV OFFICE! OF N.2 lOO.OOmL 2 0 jul 2000 received T84l7CS1.500/EB/nk Manufacturing Instructions: 1. In one vessel use 1/3 volume of warm water dissolve the PEG 6000. 2. Separately warm the Tween and dissolve the moxidectin in it. The resultant solution is 5 then dispersed in the warm water and PEG 6000. 3. Suspend the praziquantel into this solution . 4. Add the benzyl alcohol or other preservative.

. The suspension is made up to volume and other ingredients added. 6. Finally the pH is adjusted to 7.5 .

VARIATIONS The inclusion of macrolides other than abamectin as outlined in the example will necessitate variation of the above to compensate for the modified solubility properties of the new macrolide. Also more that one macrolide may be included.

The example formulation given is suitable for administration by oral drench, the invention is 15 equally applicable to formulations suitable for administration by injection and pour on.

Finally, it will be appreciated that various other alterations and modifications may be made to the forgoing without departing from the spirit and scope of this invention.

T8417CSI ,500/EB/nk .uuu i urtL KKUPERTV 0Fc'CE OF N.Z 2 0 jul 2000 RECEIVED

Claims (19)

WE CLAIM

1. A composition suitable for administration to warm-blooded non-human animals including an effective amount of at least one macrolide and an effective amount of praziquantel in suspension, together with a wetting agent, a preservative, buffer salts, a defoaming agent, a dispersing agent and water to volume.

2. A composition as claimed in claim 1, wherein the macrolide is present in the range 0.05 to 0.5% w/v.

3. A composition as claimed in either of claims 1 or 2 wherein the macrolide is selected from the group comprising the avermectins and the milbemycins.

4. A composition as claimed in any of claims 1 to 3 wherein, macrolide is moxidectin, ivermectin, abamectin, or doramectin.

5. A composition as claimed in any of claims 1 to 4 wherein, the praziquantel is present in the range from 1-5% w/v.

6. A composition as claimed in any of claims 1 to 5 wherein, the wetting agent is present in the range of 1 -30% w/v.

7. A composition as claimed in any of claims 1 to 6 wherein, the wetting agent is selected from the group polyoxyethylated vegetable oils, polyoxyethylene sorbitan monoisostearate, and polyoxyethylene (20) sorbitan monooleate.

8. A composition as claimed in any of claims 1 to 7 wherein, the wetting agent is polyoxyethylene (20) sorbitan monooleate.

9. A composition as claimed in any of claims 1 to 8 wherein, the preservative is present in the range 0-5% w/v.

10. A composition as claimed in any of claims 1 to 9 wherein, the preservative is selected from the group benzyl alcohol, methyl paraben and formalin. iWERTV QF'CE OF N.

Z 2 0 jul 2000 T8417CSI ,500/EB/nk RECEIVED -9-

12. A composition as claimed in any of claims 1 to 11 wherein the defoaming agent is present in the range from 0.5-2% w/v.

13. A composition as claimed in any of claims 1 to 12 wherein the defoaming agent is silicon dioxide or defoaming agent RD.

14. A composition as claimed in any of claims 1 to 13 wherein the defoaming agent is silicon dioxide.

15. A composition as claimed in any of claims 1 to 14 wherein the dispersing agent is present in the range from 0-1 % w/v.

16. A composition as claimed in any of claims 1 to 15 wherein the dispersing agent is selected from the group comprising PEG 6000 and other PEG compounds.

17. A composition as claimed in any of claims 1 to 16 wherein the dispersing agent is PEG

18. A composition suitable for administration to warm blooded non-human animals, substantially as herein described.

19. A method of treatment of trematodes in warm blooded non-human animals by application of the composition as claimed in any previous claim. PIPERS Attorneys for ANCARE NEW ZEALAND LIMITED 6000. Vfi&OTY OFFICE OF N.Z. 1 5 SEP 2000 RECEIVED T8417CS1,500/F.B/nk