AU2005101039A4 - Stable Parasiticide Composition - Google Patents
Stable Parasiticide Composition Download PDFInfo
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- AU2005101039A4 AU2005101039A4 AU2005101039A AU2005101039A AU2005101039A4 AU 2005101039 A4 AU2005101039 A4 AU 2005101039A4 AU 2005101039 A AU2005101039 A AU 2005101039A AU 2005101039 A AU2005101039 A AU 2005101039A AU 2005101039 A4 AU2005101039 A4 AU 2005101039A4
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- Australia
- Prior art keywords
- acid
- amount
- composition
- tetramisole
- macrocyclic lactone
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Description
AUSTRALIA
Patents Act 1990 Jurox Pty Ltd COMPLETE SPECIFICATION INNOVATION PATENT Invention Title: Stable Parasiticide Composition The following statement is a full description of this invention including the best method of performing it known to us:- Technical Field U This invention relates to parasiticide compositions for use in the treatment of parasitic infestations of animals and in particular to compositions including tetramisoles and ,1 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 CN commonly used actives are from the chemical classes of benzimidazoles, 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 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 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.
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 tetramisoles with macrocylic lactones, to stabilize the macrocyclic lactones at an alkali 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.
m:\speci\120000\1 26-127\1261 OOcmpgrb.doc in N, The present invention provides a stable preparation containing a mixture of
O
tetramisole and macrocyclic lactone in an alkaline medium without the need for formation of an emulsion or micelle solution.
O 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 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 parasitic infections in an 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 and one or more organic acids.
Throughout this specification the word "comprise", or variations such as "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 sprayon. 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 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 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 m:\speci\120000\1 26-127\126100cmpgrb.doc n 4 Saddition, in order for the polyethylene glycols to be liquid, there molecular weight will U generally be in the range of about 300-600. However, potentially solid polyethylene glycols could be used in combination with one or more suitable co-solvents.
COne or more organic acids are included in the composition and these may be selected from the group consisting of C 1
C
6 carboxylic acid, C 2
C
6 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, 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 010 amount of 0.1 100 g/L. Preferably, they are used in an amount of from 0.2 50 g/L.
C Suitable tetramisoles include those suitable for veterinary use such as levamisole. The tetramisoles are included in an effective amount such as in an amount 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 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.
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, 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 organophosphates include, but are not limited to naphthalophos and cythioate.
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 m:\speci\120000\126-127\126100cmpgrb.doc appropriate adjuvants suitable for oral and topical veterinary preparation. Suitable 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 Modes for carrying out the invention In order to better understand the nature of this invention, a number of examples will be described.
Ingredient Example 1 Example 2 Example 3 Function g/L g/L g/L Benzimidazoles 25 25 25 Active Albendazole Mebendazole Albendazole Salicylanilides 38 38 Active Closantel Oxyclozanide Macrocyclic lactones 1 1 1 Active Abamectin Ivermectin Abamectin Tetramisoles 34 34 34 Active Levamisole Levamisole Levamisole Pyrazino -18.8 Active isoquinoline Praziquantel derivates Organophosphate 120 Active Naphthalophos Polyols 800 900 q.s. to 1 L Solvent Propylene Glycol 10 Acetic Acid organic acids Benzyl alcohol Polyvinylpyrrolidone PEG 30 2 1:1 Acetic Acid Lactic Acid 5 10 PVP-K90 Propylene Glycol 5 Acetic Acid 20 PVP-K29 Stabiliser Co-solvent Stabiliser 5 30 PVP-K29 m:\speci\120000\126-127\1261 OOcmpgrb.doc Ingredient Sodium hydroxide Water Example 1 30 Example 2 911 3 Example 3 Function pH adjustment Diluent q.s. tolIL q.s. tolIL Table 1 Ingredient Availability Ingredient Available from Albendazole Pacific Resources International Pty Ltd
("PRI'
t -Mebendazole
PRI
Closantel PRI -Oxyclosanide
PRI
-Abamnectin
PRI
Ivermectin
PMI
Levamisole PRI -Praziguantel
PRI
-Napthalophos
PRI
-Propylene glycol
PRI
PEG 30 PMI Acetic acid Asia Pacific Specialty Ltd ("APS") Lactic acid -APS -Benzyl alcohol
APS
_PVP-K29, K90 Redox Chemicals Sodiumn hydroxide
APS
In examples 1, 2 and 3, tetramisoles and macrocyclic lactones were dissolved in the polyols. Other actives and excipients were then be added to the mixture. The final mixture was adjusted to pH 7.0 9.0 by using the organic acid followed by homogenisation until uniform.
m:\speci\1 20000\1 26-1 27\1 261O0cmpgrb.doc Table 2 Stability Evaluation of Example 1 Storage Time Abendazole Abamectin Levamisole Closantel g/L g/L g/L g/L Temperature Temperature Temperature Temperature 0 C 30 0 C 30 0 C 30 0
C
Initial 26.2 0.95 33.7 40.9 1 month 25.8 0.95 34.0 40.6 The stability of Example 1 was evaluated by storing samples for various times at 0 C. The results of the stability trial is set out in Table 2 from which it can be seem that the samples were stable for the time tested. The result for levamisole is within allowable analytical error.
It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.
m:\speci\120000\126-127\1261 OOcmpgrb.doc
Claims (3)
- 2. The composition according to claim 1 wherein the at least one polyol is selected C from the group consisting of propylene glycol, glycerol, sorbitol and polyethylene glycol, preferably propylene glycol and mixtures thereof; the at least one organic acid is selected from the group consisting of C 1 C 6 carboxylic acid and C 2 C 6 dicarboxylic acid, preferably methanoic acid, ethanoic acid, lactic acid, propionic acid, caproic acid, ethandioic acid, hexanedioic acid and mixtures thereof.
- 3. The composition according to claim 1 or claim 2 wherein the at least one polyol is in an amount of from 800 to 980 g/L and the at least one organic acid is in an amount of 0.2 50 g/L.
- 4. The composition according to any one of claims 1 to 3 wherein the at least one tetramisole is in an amount of from 5 to 250 g/L, preferably from 10 to 50 g/L; and the at least one macrocyclic lactone is in an amount of from 0.1 to 10 g/L, preferably from to 2.0 g/L. The use of a liquid composition having a pH of at least 7, which composition comprises one or more 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. Dated this twentieth day of December 2005 Jurox Pty Ltd Patent Attorneys for the Applicant: F B RICE CO m:\speci\120000\1 26-127\1261 OOcmpgrb.doc
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2005101039A AU2005101039B4 (en) | 2005-12-20 | 2005-12-20 | Stable Parasiticide Composition |
NZ54674706A NZ546747A (en) | 2005-12-20 | 2006-04-26 | Stable parasiticide composition |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2005101039A AU2005101039B4 (en) | 2005-12-20 | 2005-12-20 | Stable Parasiticide Composition |
Publications (2)
Publication Number | Publication Date |
---|---|
AU2005101039A4 true AU2005101039A4 (en) | 2006-02-02 |
AU2005101039B4 AU2005101039B4 (en) | 2006-03-30 |
Family
ID=35940874
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU2005101039A Expired AU2005101039B4 (en) | 2005-12-20 | 2005-12-20 | Stable Parasiticide Composition |
Country Status (2)
Country | Link |
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AU (1) | AU2005101039B4 (en) |
NZ (1) | NZ546747A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2744495B1 (en) | 2011-08-16 | 2017-01-18 | Virbac | Anthelmintic formulations and treatments |
-
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
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2744495B1 (en) | 2011-08-16 | 2017-01-18 | Virbac | Anthelmintic formulations and treatments |
Also Published As
Publication number | Publication date |
---|---|
NZ546747A (en) | 2006-10-27 |
AU2005101039B4 (en) | 2006-03-30 |
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FGI | Letters patent sealed or granted (innovation patent) | ||
MK22 | Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry |