NZ546747A - Stable parasiticide composition - Google Patents
Stable parasiticide compositionInfo
- Publication number
- NZ546747A NZ546747A NZ54674706A NZ54674706A NZ546747A NZ 546747 A NZ546747 A NZ 546747A NZ 54674706 A NZ54674706 A NZ 54674706A NZ 54674706 A NZ54674706 A NZ 54674706A NZ 546747 A NZ546747 A NZ 546747A
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- New Zealand
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Abstract
Disclosed are parasiticidal compositions having a pH of at least 7, the composition comprising an effective amount of at least one tetramisole, an effective amount of at least one macrocyclic lactone, at least one polyol in an amount of 400-980 g/L, at least one organic acid in an amount of 0.1 to 100 g/L, and optionally an effective amount of at least one benzimidazole, salicylanilide, pyrazino isoquinoline derivative, organophosphate or mixture thereof. The compositions are used in methods of treating parasitic infections in warm-blooded animals.
Description
New Zealand Paient Spedficaiion for Paient Number 546747
5467 4 7
1
Stable Parasiticide Composition Technical Field
This invention relates to parasiticide compositions for use in the treatment of parasitic infestations of animals and in particular to compositions including tetramisoles and macrocyclic lactones.
Background art
Insecticide and parasiticide compositions are commonly used in the veterinary field to deliver active substances for controlling pests in and on animals. There are a number of parasiticide actives that are known to be used in this type of treatment. The commonly used actives are from the chemical classes of benzimidazoles, 15 salicylanilides, macrocyclic lactones, tetramisoles, pyrazino isoquinoline derivative and organophosphates. A combination of actives is often employed as a combination can be more effective than treatment with a single active in the face of resistant parasites and the use of combinations may help to delay the development of resistance.
It has been difficult to formulate liquid formulations which contain a mixture of 20 some classes of actives due to chemical incompatibility between active compounds, hydrolysis, low solubility of the active compounds and instability at alkali pH.
When formulating a preparation containing tetramisoles and macrocyclic lactones, traditional formulations require micelles or emulsions to stabilise the macrocyclic lactones at alkaline pH or the use of a salt of tetramisole in an acidic 25 medium. Emulsions and micelle solutions contain large amounts of surfactants and tend to create foaming problems during manufacturing and use in the field. Emulsions and micelle solutions tend to foam when agitated during transport or shaking. Foaming traps air bubbles in the product and therefore a 30 ml dose may be altered to contain for example, 25 mL liquid and 5 mL air. This may cause non-uniformity in dose volume. 30 Emulsions may also suffer from emulsion breakdown at high or low storage temperature, which causes break down of the formulation.
Disclosure of invention
Tetramisoles have a high alkali pH . It is desirable therefore when combining 35 tetramisoles with macrocylic lactones, to stabilize the macrocyclic lactones at an alkali m :\speci\120000\126-127\127718spc.doc
*10051229460*
2
pH but at the same time to ensure that tetramisoles are also stable and prevented from crystallising out of solution in a low alkali environment.
The present invention provides a stable preparation containing a mixture of tetramisole and macrocyclic lactone in an alkaline medium without the need for 5 formation of an emulsion or micelle solution.
In a first aspect the present invention provides a parasiticidal composition having a pH of at least 7, said composition comprising an effective amount of at least one tetramisole and at least one macrocyclic lactone; one or more polyols, and one or more organic acids.
The present inventor has surprisingly found that polyols and organic acids may be used to stabilise a parasitical preparation containing a mixture of actives including macrocyclic lactones and tetramisoles.
In another aspect therefore, the invention provides the use of a liquid composition having a pH of at least 7, which composition comprises one or more 15 polyols and one or more organic acids, to stabilise at least one tetramisole and at least one macrocyclic lactone and to facilitate the administration of a parasiticidally effective amount of said at least one tetramisole and at least one macrocyclic lactone to an animal.
In yet another aspect, the present invention provides a method for treating 20 parasitic infections in an animal comprising administering to the animal a parasticidally effective amount of a composition having a pH of at least 1, said composition comprising at least one tetramisole, at least one macrocyclic lactone, one or more polyols and one or more organic acids.
Throughout this specification the word "comprise", or variations such as 25 "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
The composition of the present invention is suitable for oral and/or topical administration to an animal for example in the form of a drench, a pour-on or a spray-30 on. The composition may also be administered as an injection including subcutaneous and intramuscular injection.
The pH of the composition is at least 7, preferably in the range of from 7 to 12 and more preferably in the range of from 7 to 9.
One or more polyols are included in the composition and these may be selected 35 from the group consisting of propylene glycol, glycerol, sorbitol, polyethylene glycol and mixtures thereof. Broadly, the polyols may be included in an amount of from 400
m:\speci\120000\126-127\127718spc.doc
3
to 980 g/L. Preferably, they are used in an amount of from 800 to 980 g/L. In the case of sorbitol, it is usual to provide the sorbitol as a 70% w/v aqueous solution. In addition, in order for the polyethylene glycols to be liquid, there molecular weight will generally be in the range of about 300-600. However, potentially solid polyethylene 5 glycols could be used in combination with one or more suitable co-solvents.
One or more organic acids are included in the composition and these may be selected from the group consisting of C] - C(, carboxylic acid, C2- Ce dicarboxylic acid and mixtures thereof. Suitable organic acids include but are not limited to, methanoic acid, ethanoic acid, lactic acid, propionic acid, caproic acid, ethandioic acid, 10 hexanedioic acid and mixtures thereof. Preferred are lactic acid and ethanoic acid and most preferred is ethanoic acid. Broadly, the organic acids may be included in an amount of 0.1 - 100 g/L. Preferably, they are used in an amount of from 0.2 - 50 g/L.
Suitable tetramisoles include those suitable for veterinary use such as levamisole. The tetramisoles are included in an effective amount such as in an amount 15 from 5 to 250 g/L, preferably from 10 to 50 g/L.
The macrocyclic lactones include those suitable for veterinary use and may be selected from the group consisting of ivermectin, avermectin, doramectin, milbemycin oxime, moxidectin and mixtures thereof. As used herein, the term "avermectin" refers to avermectin Bl, also known as abamectin, being a mixture containing avermectin 20 Bla and avermectin Bib. The macrocyclic lactones are included in an effective amount such as in an amount from 0.1 to 10 g/L, preferably, from 0.5 to 2.0 g/L.
The composition of the present invention may include one or more other parasiticide actives such as those from the chemical classes of benzimidazoles, salicylanilides, pyrazino isoquinoline derivatives and organophosphates. 25 Benzimidazoles, salicylanilides and pyrazino isoquinoline derivatives may each be included in the composition in amounts of from 5 to 250 g/L, preferably 10 to 50 g/L. Organophosphates may be included in amounts of from 20 to 400g/L, preferably 70 to 200 g/L.
Suitable benzimidazoles include, but are not limited to thiabendazole, 30 cambendazole, parbendazole, mebendazole, fenbendazole, oxfendazole, oxibendazole, albendazole, albendazole sulfoxide, thiophanate, febantel, netobimin, and triclabendazole. Suitable salicylanilides include, but are not limited to brotianide, clioxanide, closantel, niclosamide, oxyclozanide and rafoxanide. Suitable pyrazino isoquinoline derivative include, but are not limited to praziquantel. Suitable 35 organophosphates include, but are not limited to naphthalophos and cythioate.
m:\speci\120000\126-127\127718spc.doc
4
Veterinarily acceptable excipients and adjuvants may be included in the composition such as solvents, stabilisers, pH adjusters, dyes, flavouring agents, preservatives and thickening agents. A person skilled in the art would be well aware of appropriate adjuvants suitable for oral and topical veterinary preparation. Suitable 5 thickening agents include xanthan gum, colloidal silicon dioxide, cellulose gum, guar gum. Polyvinylpyrrolidone (PVP) may be used as a stabiliser. Preferred PVP's are those with a K value of 12 to 97 such as PVP-K15, PVP-K30 and PVP-K90.
Modes for carrying out the invention
In order to better understand the nature of this invention, a number of examples will be described.
Ingredient
Benzimidazoles
Salicylanilides
Macrocyclic lactones
Tetramisoles
Pyrazino isoquinoline derivates Organophosphate
Polyols organic acids
Example 1 g/L
Albendazole 38
Closantel 1
Abamectin 34
Levamisole
800
Propylene
Glycol
Acetic Acid
Example 2 g/L
Mebendazole
1
Ivermectin 34
Levamisole 18.8
Praziquantel
900
PEG 30
Example 3 g/L
Albendazole 38
Oxyclozanide 1
Abamectin 34
Levamisole
120
Naphthalophos q.s. to 1 L Propylene Glycol
Benzyl alcohol
2 5
1:1 Acetic Acetic Acid
Acid / Lactic
Acid
Function
Active Active Active Active Active
Active Solvent
Stabiliser
Co-solvent m:\speci\120000\126-127\127718spc.doc
Polyvinylpyrrolidone 30 10 20
PVP-K29 PVP-K90 PVP-K29
Stabiliser
Ingredient
Sodium hydroxide 30
Water
Example 1 Example 2 Example 3 g/L g/L g/L
3
q.s. to 1 L q.s. to 1 L
Function pH
adjustment Diluent
Table 1 - Ingredient Availability
Ingredient *"
Available from
Hi- ■••••• •••.
Albendazole
Pacific Resources International Pty Ltd ("PRI")
Mebendazole
PRI
Closantel
PRI
Oxyclosanide
PRI
Abamectin
PRI
Ivermectin
PRI
Levamisole
PRI
Praziquantel
PRI
Napthalophos
PRI
Propylene glycol
PRI
PEG 30
PRI
Acetic acid
Asia Pacific Specialty Chemicals Ltd ("APS")
Lactic acid
APS
Benzyl alcohol
APS
PVP-K29, K90
Redox Chemicals
Sodium hydroxide
APS
In examples 1, 2 and 3, tetramisoles and macrocyclic lactones were dissolved in 5 the polyols. Other actives and excipients were then be added to the mixture. The final m:\speci\120000\126-127\127718spc.doc
6
mixture was adjusted to pH 7.0 - 9.0 by using the organic acid followed by homogenisation until uniform.
m:\speci\120000\126-127\127718spc.doc
Claims (48)
- I. A parasiticidal composition having a pH of at least 7, said composition comprising: an effective amount of at least one tetramisole; 5 an effective amount of at least one macrocyclic lactone; at least one polyol in an amount of from 400-980 g/L; at least one organic acid in an amount from 0.1 to 100 g/L; and optionally, an effective amount of at least one benzimidazole, salicylanilide, pyrazino isoquinoline derivative, organophosphate or mixture thereof. 10
- 2. The composition according to claim 1 wherein the at least one polyol is selected from the group consisting of propylene glycol, glycerol, sorbitol, polyethylene glycol and mixtures thereof; and the at least one organic acid is selected from the group consisting of Ci - C(, carboxylic acid, Cj-Cf, dicarboxylic acid and mixtures thereof.
- 3. The composition according to claim 1 wherein the at least one polyol is 15 propylene glycol.
- 4. The composition according to claim 1 wherein the at least one organic acid is selected from the group consisting of methanoic acid, ethanoic acid, lactic acid, propionic acid, caproic acid, ethandioic acid, hexanedioic acid and mixtures thereof.
- 5. The composition according to claim 1 wherein the at least one organic acid is 20 selected from the group consisting of lactic acid, ethanoic acid and mixtures thereof.
- 6. The composition according to any one of claims 1 to 5 wherein the at least one polyol is in an amount of from 800 to 980 g/L.
- 7. The composition according to any one of claims 1 to 6 wherein the at least one organic acid is in an amount of 0.2 - 50 g/L. 25 8. The composition according to any one of claims 1 to 7 having a pH of from 7 to 12.
- 9. The composition according to any one of claims 1 to 7 having a pH of from 7 to
- 9.
- 10. The composition according to any one of claims 1 to 9 wherein the at least one 30 tetramisole is in an amount of from 5 to 250 g/L
- II. The composition according to any one of claims 1 to 9 wherein the at least one tetramisole is in an amount of from 10 to 50 g/L.
- 12. The composition according to any one of claims 1 to 11 wherein the at least one macrocyclic lactone is in an amount of from 0.1 to 10 g/L. 35
- 13. The composition according to any one of claims 1 to 11 wherein the at least one macrocyclic lactone is in an amount of from 0.5 to 2.0 g/L. m:\speci\120000\126-127\127718spc.doc 9 10 15 20 25 30
- 14. The composition according to any one of claims 1 to 13 comprising at least one benzimidazole, salicylanilide and/or pyrazino isoquinoline derivative, respectively in an amount of from 5 to 250 g/L.
- 15. The composition according to any one of claims 1 to 13 comprising at least one benzimidazole, salicylanilide and/or pyrazino isoquinoline derivative, respectively in an amount of from 10 to 50 g/L.
- 16. The composition according to any one of claims 1 to 15 comprising at least one organophosphate in an amount of from 20 to 400g/L.
- 17. The composition according to any one of claims 1 to 15 comprising at least one organophosphate in an amount of from 70 to 200g/L.
- 18. The composition according to any one of claims 1 to 17 comprising at least one benzimidazole selected from the group consisting of thiabendazole, cambendazole, parbendazole, mebendazole, fenbendazole, oxfendazole, oxibendazole, albendazole, albendazole sulfoxide, thiophanate, febantel, netobimin, and triclabendazole.
- 19. The composition according to any one of claims 1 to 18 comprising at least one salicylanilide selected from the group consisting of brotianide, clioxanide, closantel, niclosamide, oxyclozanide and rafoxanide.
- 20. The composition according to any one of claims 1 to 19 comprising at least one pyrazino isoquinoline derivative such as praziquantel.
- 21. The composition according to any one of claims 1 to 20 comprising at least one organophosphate selected from the group consisting of naphthalophos and cythioate.
- 22. The use of a liquid composition having a pH of at least 7, which composition comprises one or more polyols in an amount of from 400 to 980g/L and one or more organic acids in an amount of from 0.1 to lOOg/L, to stabilise at least one tetramisole and at least one macrocyclic lactone and to facilitate the administration of a parasiticidally effective amount of said at least one tetramisole and at least one macrocyclic lactone to an animal.
- 23. Use according to claim 22 wherein the at least one polyol is selected from the group consisting of propylene glycol, glycerol, sorbitol, polyethylene glycol and mixtures thereof; and the at least one organic acid is selected from the group consisting of Ci - C6 carboxylic acid, C2- C6 dicarboxylic acid and mixtures thereof.
- 24. Use according to claim 22 wherein the at least one polyol is propylene glycol.
- 25. Use according to claim 22 wherein the at least one organic acid is selected from the group consisting of methanoic acid, ethanoic acid, lactic acid, propionic acid, caproic acid, ethandioic acid, hexanedioic acid and mixtures thereof. m:\speci\120000\126-127\127718clmgrb.doc 0 6 JUN 2006 RECEIVED 10 10 15 20 25 30
- 26. Use according to claim 22 wherein the at least one organic acid is selected from the group consisting of lactic acid, ethanoic acid and mixtures thereof.
- 27. Use according to any one of claims 22 to 26 wherein the at least one polyol is in an amount of from 800 to 980 g/L.
- 28. Use according to any one of claims 22 to 27 wherein the at least one organic acid is in an amount of 0.2 - 50 g/L.
- 29. Use according to any one of claims 22 to 28 wherein the composition has a pH of from 7 to 12.
- 30. Use according to any one of claims 22 to 28 wherein the composition has a pH of from 7 to 9.
- 31. Use according to any one of claims 22 to 30 wherein the at least one tetramisole is in an amount of from 5 to 250 g/L.
- 32. Use according to any one of claims 22 to 30 wherein the at least one tetramisole is in an amount of from 10 to 50 g/L
- 33. Use according to any one of claims 22 to 32 wherein the at least one macrocyclic lactone is in an amount of from 0.1 to 10 g/L.
- 34. Use according to any one of claims 22 to 32 wherein the at least one macrocyclic lactone is in an amount of from 0.5 to 2.0 g/L.
- 35. A method for treating parasitic infections in a warm-blooded non-human animal comprising administering to the animal a parasticidally effective amount of a composition having a pH of at least 7, said composition comprising at least one tetramisole, at least one macrocyclic lactone, one or more polyols in an amount of from 400 to 980g/L and one or more organic acids in an amount of from 0.1 to lOOg/L.
- 36. A method according to claim 35 wherein the at least one polyol is selected from the group consisting of propylene glycol, glycerol, sorbitol, polyethylene glycol and mixtures thereof; and the at least one organic acid is selected from the group consisting of Ci - C6 carboxylic acid, C2-C6 dicarboxylic acid and mixtures thereof.
- 37. A method according to claim 35 wherein the at least one polyol is propylene glycol.
- 38. A method according to claim 35 wherein the at least one organic acid is selected from the group consisting of methanoic acid, ethanoic acid, lactic acid, propionic acid, caproic acid, ethandioic acid, hexanedioic acid and mixtures thereof.
- 39. A method according to claim 35 wherein the at least one organic acid is selected from the group consisting of lactic acid, ethanoic acid and mixtures thereof.
- 40. A method according to any one of claims 35 to 39 wherein the at least one polyol is in an amount of from 800 to 980 g/L. m:\speci\120000\126-127\127718clmgrb.doc 0 6 JUN 2006 11
- 41. A method according to any one of claims 35 to 40 wherein the at least one organic acid is in an amount of 0.2 - 50 g/L.
- 42. A method according to any one of claims 35 to 41 wherein the composition has apH of from 7 to 12.
- 43. A method according to any one of claims 35 to 41 wherein the composition has a pH of from 7 to 9.
- 44. A method according to any one of claims 35 to 43 wherein the at least one tetramisole is in an amount of from 5 to 250 g/L.
- 45. A method according to any one of claims 35 to 43 wherein the at least one tetramisole is in an amount of from 10 to 50 g/L
- 46. A method according to any one of claims 35 to 43 wherein the at least one macrocyclic lactone is in an amount of from 0.1 to 10 g/L.
- 47. A method according to any one of claims 35 to 43 wherein the at least one macrocyclic lactone is in an amount of from 0.5 to 2.0 g/L.
- 48. A parasiticidal composition substantially as herein before defined with reference to any one of the examples. Dated this 31st day of May 2006. Jurox Pty Ltd Patent Attorneys for the Applicant: F B RICE & CO m:\speci\120000\126-127\127718clmgrb.doc
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2005101039A AU2005101039B4 (en) | 2005-12-20 | 2005-12-20 | Stable Parasiticide Composition |
Publications (1)
Publication Number | Publication Date |
---|---|
NZ546747A true NZ546747A (en) | 2006-10-27 |
Family
ID=35940874
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NZ54674706A NZ546747A (en) | 2005-12-20 | 2006-04-26 | Stable parasiticide composition |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU2005101039B4 (en) |
NZ (1) | NZ546747A (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ594610A (en) | 2011-08-16 | 2013-03-28 | Virbac New Zealand Ltd | Injectable Anthelmintic Formulations cotaining levamisole and one or more macrocyclic lactones for controlling internal parasites in ruminants |
-
2005
- 2005-12-20 AU AU2005101039A patent/AU2005101039B4/en not_active Expired
-
2006
- 2006-04-26 NZ NZ54674706A patent/NZ546747A/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
AU2005101039A4 (en) | 2006-02-02 |
AU2005101039B4 (en) | 2006-03-30 |
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