AU2007202548B1

AU2007202548B1 - Pesticide Composition

Info

Publication number: AU2007202548B1
Application number: AU2007202548A
Authority: AU
Inventors: Kai Kin Lau
Original assignee: Zoetis Services LLC
Current assignee: Zoetis Services LLC
Priority date: 2007-06-01
Filing date: 2007-06-01
Publication date: 2007-11-01
Anticipated expiration: 2027-06-01
Also published as: GB2449746B8; GB2449746A8; GB2449746A; GB0809203D0; IE20080400A1; GB2449746B

Description

AUSTRALIA

Patents Act 1990 JUROX PTY LTD COMPLETE SPECIFICATION STANDARD PATENT Invention Title.

Pesticide Composition The following statement is a full description of this invention including the best method of performing it known to us:-

O

c-2-

C)

00Technical Field SThis invention relates to insect growth regulator (IGR) compositions for external use in the prevention and control of insect and acarid infestations of animals and in particular to diazine and triazine IGR compositions.

N Background art The diazine and triazine IGR's of low water solubility are generally provided as a wettable powder, a suspension concentrate or a dilute aqueous solution. The wettable powder has the disadvantage that it is dusty and therefore poses a hazard to persons handling the product at the time of manufacture or at the time of application. The suspension concentrate suffers from sedimentation and caking during storage and requires vigorous shaking of the product before use. Uniformity of dosing can be adversely affected by insufficient shaking prior to use or during prolonged continuous use, resulting in under- or overdosing. The suspension concentrate may also increase in viscosity at low temperatures requiring more force to dispense through a drenching gun thus causing difficulty in dispensing. The wettable powder and suspension concentrate are generally diluted with water prior to use. The dilute aqueous solution, on the other hand, is generally used without further dilution. The dilute aqueous formulations have a low active content and contain a large amount of water. As a result, transportation of the product to an end user may be cumbersome and costly.

Disclosure of invention It is desirable to provide a formulation that can support a high concentration of a diazine or triazine IGR in solution, a formulation which may be diluted with water as required and may be applied topically.

Accordingly, in a first aspect, the present invention provides a composition comprising an effective amount of an IGR of formula (I)

SH

2

N

N= R 1 R4 N N R2

R

3 Swherein R| is hydrogen, CI-C 6 alkyl, C 2

-C

6 alkenyl or C 2

-C

6 alkynyl,

SR

2 is hydrogen, Ci-Clo alkyl or C 3

-C

6 cycloalkyl, or a radical selected from the group consisting of-(CH 2 3

-(CH

2 4 and -(CH 2

R

3 is a radical selected from the group consisting of-NH 2 and -NH-CO-H, and

R

4 is C-CN or N; one or more organic solvents selected from the group consisting of polyols, glycol ethers, glycerol ether acetates, CI-C 8 alkyl pyrrolidones, acetal and mixtures thereof; one or more organic acids selected group consisting of Ci-C 6 carboxylic acids, C 2

-C

6 dicarboxylic acids and mixtures thereof; and optionally one or more surfactants.

In the composition of the present invention, the IGR of formula is solubilised thus avoiding the problems of a wettable powder or suspension as discussed above.

The composition may be used neat or diluted with water prior to use.

Accordingly, in a second aspect, the invention provides a method of preventing or controlling insect and acarid infestations of a warm blooded animal, the method comprising topically administering to the animal a composition comprising an effective amount of an IGR of formula (as defined above); one or more organic solvents selected from the group consisting of polyols, glycol ethers, glycerol ether acetates, Ci-

C

8 alkyl pyrrolidones, acetal and mixtures thereof; one or more organic acids selected group consisting of CI-C 6 carboxylic acids, C 2

-C

6 dicarboxylic acids and mixtures thereof; and optionally one or more surfactants, wherein said method optionally comprises diluting the composition with water prior to topically administering to the animal.

In a third aspect, the present invention is directed to use of an effective amount of an IGR of formula (as defined above) which is solubilised in a composition which consists essentially of: one or more organic solvents selected from the group consisting of polyols, glycol ethers, glycerol ether acetates, CI-C 8 alkyl pyrrolidones, acetal and mixtures thereof; 498284_ .doc -4c4 one or more organic acids selected group consisting of Ci-C 6 carboxylic acids, C 2

-C

6 dicarboxylic acids and mixtures thereof; and optionally, one or more surfactants, O in the preparation of a composition for preventing or controlling insect and acarid infestations of a warm blooded non human animal.

0 Throughout this specification the word "comprise", or variations such as tt "comprises" or "comprising", will be understood to imply the inclusion of a stated 0 element, integer or step, or group of elements, integers or steps, but not the exclusion of r any other element, integer or step, or group of elements, integers or steps.

Throughout this specification, the term "consisting essentially of' is intended to I exclude elements which would materially affect the properties of the claimed composition.

The IGR is preferably a diazine of formula (II):

H

2

N

N R1

N

N R2 R3 wherein RI is hydrogen, CI-C 6 alkyl, C 2

-C

6 alkenyl or C 2

-C

6 alkynyl,

R

2 is hydrogen, Ci-Clo alkyl or C 3

-C

6 cycloalkyl, or a radical selected from the group consisting of-(CH2) 3

-(CH

2 4 and -(CH 2 5 and

R

3 is a radical selected from the group consisting of-NH 2 and -NH-CO-H.

More preferably, in formulae and Ri is hydrogen, R 2 is C 3

-C

6 cycloalkyl and R 3 is -NH 2 Most preferred IGR's are 4,6-diamino-2-cyclopropylaminopyrimidine- 5-carbonitrile (dicyclanil) and N-cyclopropyl-l,3,5-triazine-2,4,6-triamine (cyromazine).

Cyromazine and dicyclanil respectively, may be included in the composition of the present invention in a concentration of up to 400g/L. The composition is suitable for topical administration to an animal, for example as a dip, a pour-on, a spray-on or a jetting formulation. The composition may be diluted with water prior to use and the level of dilution will vary with the initial concentration of cyromazine and the selected method of application. The cyromazine and dicyclanil respectively, may be included in the composition of the t- invention in an amount of from 10g/L to 400g/L, preferably an amount of from 1OOg/L to 300g/L.

The one or more organic solvents included in the composition are selected from O the group consisting of polyols, glycol ethers, glycerol ether acetates, CI-Cg alkyl pyrrolidones, acetal and mixtures thereof. Suitable polyols include but are not limited 00 to propylene glycol, glycerol and polyethylene glycol. Suitable glycol ethers include t) but are not limited to dipropylene glycol monomethylether, butyl icinol and butyl di 0 icinol. Suitable glycerol ether acetates include but are not limited to ethylene glycol monobutylether acetate and propylene glycol monoethyl ether acetate. Suitable Ci-C 8 alkyl pyrrolidones include but are not limited to N-methyl pyrrolidone, 1-octyl-2 N pyrrolidinone and lauryl pyrrolidone. Suitable acetal include but are not limited to glycerol formal and tetraglycol. Preferably the organic solvents are selected from one or more of glycerol formal, tetraglycol and propylene glycol. More preferably, the solvent is a mixture of propylene glycol with glycerol formal or tetraglycol.

The total concentration of the solvent may be in the range of from 200 to 900g/L, preferably from 300 to 600g/L.

One or more organic acids are included in the composition of the invention selected from the group consisting of CI-C 6 carboxylic acids, C 2

-C

6 dicarboxylic acids and mixtures thereof. Suitable organic acids include but are not limited to formic acid, acetic acid, lactic acid, propionic acid, caproic acid ethandioic acid, hexanedioic acid and mixtures thereof. Preferred are lactic acid and acetic acid and most preferred is lactic acid.

The acid may be included in a concentration in the range of from 10 to 300g/L, preferably 100 to 200g/L.

The composition optionally contains one or more surfactants. The one or more surfactants may be selected from nonionic surfactants such as Cs-Clo alkylphenyl ethoxylates such as ethoxylated nonylphenyl and ethoxylated octylphenyl, sorbitan fatty acid ester ethoxylates such as polyoxyethylene sorbitan fatty acid esters.

The Cs-Clo alkyl phenyl ethoxylates preferably contain from 2 to 100 moles of ethylene oxide and may be selected from the commercially available Teric series products such as those identified as Teric N9 and Teric X8. The sorbitan fatty acid ester ethoxylates preferably contain from 4 to 20 moles of ethylene oxide and may be selected from polysorbate 60 and polysorbate Preferably the surfactant is present in the composition at a concentration in the range of from 10 to 200g/L, more preferably in the range of from 30 to 1OOg/L.

498284_1.doc NI Veterinarily acceptable excipients and adjuvants may be included in the composition such as colour, thickening agent, anti foaming agent and preservative.

Description of the Drawings Figure l a shows dose (ppm) against larvae survival numbers for a composition 00 of the present invention (RD183) for assay 1 of in vitro tests as described in example 7 t below.

Figure l b shows dose (ppm) against larvae survival numbers for a composition N of the present invention (RD184) for assay 1 of in vitro tests as described in example 7 below.

r Figure Ic shows dose (ppm) against larvae survival numbers for a comparative composition not of the present invention for assay 1 of in vitro tests as described in example 7 below.

Figure 2a shows dose (ppm) against larvae survival numbers for a composition of the present invention (RD183) for assay 2 of in vitro tests as described in example 7 below.

Figure 2b shows dose (ppm) against larvae survival numbers for a composition of the present invention (RD184) for assay 2 of in vitro tests as described in example 7 below.

Figure 2c shows dose (ppm) against larvae survival numbers for a comparative composition not of the present invention for assay 2 of in vitro tests as described in example 7 below.

Figure 3a shows dose (ppm) against percent larval mortality for a composition of the present invention (RD 183) for assay 2 of in vitro tests as described in example 7 below.

Figure 3b shows dose (ppm) against percent larval mortality for a composition of the present invention (RD184) for assay 2 of in vitro tests as described in example 7 below.

Figure 3c shows dose (ppm) against percent larval mortality for a comparative composition not of the present invention for assay 2 of in vitro tests as described in example 7 below.

Modes for carrying out the invention In order to better understand the nature of this invention a number of examples will be described.

498284 l.doc Example 1 Quantity Supplier Cyromazine 260 g/L Pacific Resource Teric N9 45 g/L ICI Acetic Acid 118 g/L Sigma Chemicals Tetraglycol 500 g/L Tiger Chemicals Propylene glycol q.s. to 1 L Pacific Resource Example 2 Quantity Supplier Cyromazine 300 g/L Pacific Resource Teric N9 50 g/L ICI Acetic Acid 10 g/L Sigma Chemicals Glycerol Formal 500 g/L Tiger Chemicals Lactic Acid 100 g/L Sigma Chemicals Propylene glycol q.s. to 1 L Pacific Resource The formulations of Example 1 and 2 were prepared by dissolving cyromazine in a mixture of the surfactant, organic solvent and acid followed by high speed mixing until uniform.

Example 3 Quantity Supplier Dicyclanil 250 g/L Tiger Chemicals Teric N9 45 g/L ICI Acetic Acid 200 g/L Sigma Chemicals Tetraglycol 300 g/L Tiger Chemicals Propylene glycol q.s. to 1 L Pacific Resource Example 4 Quantity Supplier Dicyclanil 50 g/L Tiger Chemicals Teric N9 50 g/L ICI Acetic Acid 50 g/L Sigma Chemicals Glycerol Formal 500 g/L Tiger Chemicals Lactic Acid 100 g/L Sigma Chemicals Propylene glycol q.s. to 1 L Pacific Resource 498284_1.doc Example Quantity Supplier Dicyclanil 100 g/L Tiger Chemicals Teric N9 50 g/L ICI Acetic Acid 50 g/L Sigma Chemicals Glycerol Formal 300 g/L Tiger Chemicals Lactic Acid 100 g/L Sigma Chemicals Propylene glycol 100 g/L Pacific Resource Water q.s. to 1 L Example 6 Quantity Supplier Dicyclanil 100 g/L Tiger Chemicals Teric N9 50 g/L ICI Acetic Acid 50 g/L Sigma Chemicals Glycerol Formal 200 g/L Tiger Chemicals Lactic Acid 100 g/L Sigma Chemicals N-methylpyrrolidone 200 g/L Pacific Resource Water q.s. to 1 L The formulations of Example 3-5 were prepared by dissolving dicyclanil in a mixture of the surfactant, organic solvent and acid followed by high speed mixing until uniform. Where applicable, the final volume is made up with water.

Example 7 The relative activity of three dicyclanil formulations was assessed against 1st instar Lucilia cuprina larvae using an in vitro chromatography paper test system. The study compared two formulations of the present invention RD183 and RD184 described below, with a reference formulation labelled as formulation RD185.

RD 183 Quantity Supplier Dicyclanil 50 g/L Tiger Chemicals Teric X 15 g/L ICI Acetic Acid 150 g/L Sigma Chemicals Glycerol Formal 200 g/L Tiger Chemicals Water q.s. to L 498284_ .doc 0

O

-9- RD184 Quantity Supplier Dicyclanil 50 g/L Tiger Chemicals Teric X 15 g/L ICI Propylene Glycol 50 g/L Pacific Resource Glycerol Formal 20 g/L Tiger Chemicals Lactic Acid 150 g/L Sigma Chemicals N-methylpyrrolidone 20 g/L Pacific Resource Water q.s. to 1 L Reference formulation RD185 dicyclanil suspension 50g/L dicyclanil Method Each experimental formulation was dissolved in acetone and mixed in blood serum to give the desired range of test concentrations. The concentrations used in the assays are shown in Figures 1 and 2. Dilutions in serum were prepared the day before commencement of the assay and allowed to sit in a fumehood overnight to allow the solvent to evaporate. A method approximately similar to that described by Roxburgh and Shanahan (1973) (Bull. Ent. Res. 63:99) was used. Chromatography paper cut to 12cm x 3cm strips was rolled, inserted into 5cm x 1.5cm diameter flat bottom glass vials and a Iml aliquot of the test concentration in serum added to each vial. There were three replicates for each test concentration for each test formulation.

Approximately 30 freshly emerged 1st instar Lucilia cuprina larvae were added to the top of the chromatography paper and the vials covered with a filter paper top held in place with an elastic band. The vials were held in darkness at 280C and larval survival assessed at 48 h.

In assay 1 (Figs la, b, no extra serum was added. In assay 2 (Figs 2a, b, c), an extra 1 ml aliquot of the appropriate serum/test compound was added after 24h. The number of live and dead larvae was recorded and compared to the controls.

Results and interpretation Results for assay 1 (Figs la,b,c) provided a preliminary indication of larval survival, and subsequently supported in assay 2 (Figs 2a,b,c), of the approximate concentration range of activity of the different formulations.

N In assay 1, no larvae survived at concentrations above 0.02ppm for RD183. For RD184, 5 larvae survived at 0.04ppm but none at 0.16ppm. There was one larva alive at 0.64ppm. For RD185, there were 26 larvae alive at 0.04ppm, but none at any O concentrations above that (Figs 1 a, b and c).

In assay 2, a restricted range of concentrations between 0.01 and 2.56 ppm was 00 used. Larval survival is plotted for this assay to enable easy comparison with the results )n of assay 1 (Figs 2 a, b and but percent mortality for the three formulations is also Spresented (Fig 3 a, b, and c).

Assay 2 provided comparable results to assay 1 with no larvae surviving above 0.02 ppm for RD183 and RD184 (100% mortality), but 60 larvae surviving at this CN concentration for formulation RD185 (46% mortality). No larvae survived at the next highest test concentration (0.08ppm) for RD 185.

It is a surprising that formulations RD183 and RD184 of the present invention were more larvacidal than reference formulation RD185 in this assay system.

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.

498284 l.doc

Claims

1. A composition comprising: O an effective amount of a diazine of formula (II): H 2 N 00 N N R2 R3 wherein RI is hydrogen, Ci-C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, R 2 is hydrogen, Ci-Clo alkyl or C 3 -C 6 cycloalkyl, or a radical selected from the group consisting of-(CH 2 3 -(CH 2 4 and -(CH 2 )5 and R 3 is a radical selected from the group consisting of-NH 2 and -NH-CO-H; solubilised in a composition consisting essentially of one or more organic solvents selected from the group consisting of polyols, glycol ethers, glycerol ether acetates, Ci- C 8 alkyl pyrrolidones, acetal and mixtures thereof; one or more organic acids selected from the group consisting of CI-C 6 carboxylic acids, C 2 -C 6 dicarboxylic acids and mixtures thereof; and optionally one or more surfactants.

2. A composition according to claim 1 wherein in the diazine of formula R 1 is hydrogen, R 2 is C 3 -C 6 cycloalkyl and R 3 is -NH 2

3. A composition according to claim 1 wherein the diazine of formula (II) is dicyclanil.

4. A composition according to any one of claims 1 to 3, wherein the one or more organic solvents is selected from the group consisting of propylene glycol, glycerol, polyethylene glycol, dipropylene glycol monomethylether, butyl icinol, butyl diicinol, ethylene glycol monobutylether acetate, propylene glycol monoethyl ether acetate, N- methyl pyrrolidone, I-octyl-2 pyrrolidinone, lauryl pyrrolidone, glycerol formal, tetraglycol and mixtures thereof.

5. A composition according to any one of claims 1 to 4 wherein the one or more organic acids is selected from the group consisting of formic acid, acetic acid, lactic acid, propionic acid, caproic acid, ethandioic acid, hexandioic acid and mixtures thereof. -12- o 6. A composition according to any one of the preceding claims wherein the at least one C organic solvent is included in an amount of from 200 to 900g/L. O 7. A composition according to claim 6 wherein the organic solvent is included in an amount of from 300 to 600g/L. 0

8. A composition according to any one of the preceding claims wherein the organic Ssolvent is selected from one or more of glycerol formal, tetraglycol and propylene 0 glycol.

9. A composition according to any one of the preceding claims wherein the at least one organic acid is included in an amount of from 10 to 300g/L. A composition according to claim 9 wherein the organic acid is included in an amount of from 100 to 200g/L. A composition according to any one of the preceding claims wherein the organic acid is selected from lactic acid, acetic acid and mixtures thereof.

11. A method of preventing or controlling insect and acarid infestations of a warm blooded animal, the method comprising topically administering to the animal a composition comprising: an effective amount of a diazine of formula (II): H 2 N N R1 R3 wherein R 1 is hydrogen, CI-C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, R 2 is hydrogen, Ci-Clo alkyl or C 3 -C 6 cycloalkyl, or a radical selected from the group consisting of-(CH 2 3 -(CH 2 4 and -(CH 2 )5 and R 3 is a radical selected from the group consisting of-NH 2 and -NH-CO-H; solubilised in a composition consisting essentially of one or more organic solvents selected from the group consisting ofpolyols, glycol ethers, glycerol ether acetates, C 1 C 8 alkyl pyrrolidones, acetal and mixtures thereof; one or more organic acids selected group consisting of CI-C 6 carboxylic acids, C 2 -C 6 dicarboxylic acids and mixtures thereof; and optionally one or more surfactants, wherein said method optionally comprises diluting the composition with water prior to topically administering to the animal. S12. A method according to claim 11 wherein in the diazine of formula RI is Shydrogen, R 2 is C 3 -C 6 cycloalkyl and R 3 is -NH 2

13. A method according to claim 12 wherein the diazine of formula (II) is dicyclanil. 0 14.Use of an effective amount of a diazine of formula (II): H 2 N 0 N R, NC N N 2 R 3 wherein RI is hydrogen, CI-C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, R 2 is hydrogen, Ci-Cio alkyl or C 3 -C 6 cycloalkyl, or a radical selected from the group consisting of-(CH 2 3 -(CH 2 4 and -(CH 2 5 and R 3 is a radical selected from the group consisting of-NH 2 and -NH-CO-H, said diazine being solubilised in a composition which consists essentially of: one or more organic solvents selected from the group consisting of polyols, glycol ethers, glycerol ether acetates, Ci-C 8 alkyl pyrrolidones, acetal and mixtures thereof; one or more organic acids selected group consisting of CI-C 6 carboxylic acids, C 2 -C 6 dicarboxylic acids and mixtures thereof; and optionally, one or more surfactants, in the preparation of a composition for preventing or controlling insect and acarid infestations of a warm blooded animal. Use according to claim 14 wherein in the diazine of formula RI is hydrogen, R 2 is C 3 -C 6 cycloalkyl and R 3 is -NH 2

16. Use according to claim 15 wherein the diazine of formula (II) is dicyclanil.

17. A composition comprising an effective amount of dicyclanil substantially as hereinbefore described with reference to examples 3 to 7, excluding comparative examples. 498284 1.doc

18. A method of preventing or controlling insect and acarid infestations of a warm Sblooded animal, the method comprising topically administering to the animal a _dicyclanil composition substantially as hereinbefore described with reference to O examples 3 to 7, excluding comparative examples. 00 Dated this first day of June 2007 SJurox Pty Ltd Patent Attorneys for the Applicant: C F B RICE CO 498284 l.doc