AU620863B2 - Liquid pour-on formulation - Google Patents

Description

4 14 4

AUSTRALIA

Patents Act COMPLEfE SPECIFICATION

(ORIGINAL)

620863 6ft~ 6 2 o^ 0C1 Class Int. Class Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority Related Art: t Applicant(s): Sentrachem Limited Anderson Street,, Johannesburg,, Transvaal, SOUTH AFRICA 'Address for Service is: PHILLIPS OBMONDE FITZPATRICK Patent and Trade Mark Attorneys 367 Collins Street Melbourne 3000 AUSTRALIA Complete Specification for the invention entitled: LIQUID POUR-ON FORMULATION Our Ref 130703 POF Code: 1503/63545 The following statement is a full description of this invention, including the best method of performing it known to applicant(s): 1 6006 k 1 2 BACKGROUND OF THE INVENTION This invention relates to a liquid pour-on formulation, and more particularly to such a formulation for application to cattle.

A pour-on formulation is one which has an active ingredient dissolved, emulsified or suspended in a suitable solvent or solvent mixture which is tolerated by skin. The formulation is applied to the skin of the animal to be treated and allowed to run over the skin to cover a reasonable area. To be effective, such pour-on formulations generally do not need to cover che entire surface of the animal being treated.

Pour-on formulations of insecticides have been known for many years.

South African Patent No. 83/3066 describes a pour-on formulation for sheep which comprises a pyrethroid in admixture with an organic liquid carrier. Examples of suitable organic liquid carriers are paraffin oil, a glycol, a mixture of xylene, cyclohexanone, and vegetable oil, and esters and alkylamides of fatty acids. Examples of suitable pyrethroids are cypermethrin, permethrin, phenothrin, cyfluthrin, cyphenothrin, tralomethrin, tralocythrin and phenvalerate.

3 I -3- South African Patent No. 81/6661 describes an insecticidal composition comprising a non-systemic insecticide admixed with an aliphatic hydrocarbon oil. The composition is said to be capable of being applied to an animal as a pour-on. Examples of suitable non-systemic insecticides are organo phosphates, organo chlorides, formamidines and pyrethroids. The disclosure of the specification is restricted to the use of such formulations on pigs.

South African Patent No. 81/5273 describes a pour-on formulation of a compound which is active against ticks, characterised in that the formulation contains 0,1 to 30 parts by weight of the active compound, 10 to 80 parts by weight of one or more spreading oils, 20 to 95 parts by weight of one or more solvents which are tolerated by skin and 0 to 20 parts by SI weight of further auxiliaries. Examples of suitable active compounds include synthetic pyrethroids, amidines and II thioureas. Examples of suitable spreading oils are oily liquids which distribute themselves particularly readily on the skin such as silicone oils, fatty acid esters, triglycerides, fatty alcohols and fatty acids. The specification provides some in vivo test data on the use of particular formulations j *for the control of ticks on cattle.

It is an object of the present invention to provide a pour-on t formulation for the control of ticks on cattle.

SUMMARY OF THE INVENTION According to the present invention, there is provided a liquid pour-on formulation for use in the control of lice, nuisance flies and ticks on cattle comprising 0,1 to 2 percent by weight of a compound of the formula I:

CN

V C1 CzzCH CH 3

-C

V CI CH 3 7 dissolved in a liquid paraffinic oil containing less than 1 percent aromatics by weight and further including a silicone oil which is soluble in the paraffinic oil. The compound (I) C exists in various isomeric 9 9Se* 0* 09 9*@9

S

9 9 9* 99 9 99 9 9 9 9 99 DMW/3546U r i -4- C C- 4 H C CH3 S" ssolved in a liquid paraffinic oil containing less than 1 .perent apematies.-The compound exists in various -izsmcric forms. The invention covers the use of all active isomers 9* alone or in combination with inactive isomers. Particular S compounds of this formula are cypermethrin and alphamethrin.

Further according to the invention, there is provided a method of controlling lice, nuisance flies and ticks on cattle which i* comprises the application of a formulation as defined above on to the skin of cattle.

DESCRIPTION OF EMBODIMENTS The liquid pour-on formulation of the invention is designed specifically for the control of lice, nuisance flies and ticks on cattle. For this application, there are several essential features of the formulation.

First, the pyrethroid active ingredient has been found to have skin irritant properties for cattle and it is therefore essential that the liquid paraffinic oil has a low aromatics content, i.e. at least less than 1 percent aromatics by weight and preferably no aromatics at all. These paraffiiiic oils will be liquid at ambient temperature and will contain, in general, a high content of iso-paraffins. An example of a particularly suitable paraffinic oil is that sold under the trade name WHITEREX. Trials have been carried out with xylene and paraffin oils containing more than 1 percent aromatics and up to 8 percent aromatics. In all such cases the skin irritation to the cattle was unacceptably high.

Second, the active ingredient is a compound of the formula I above. Preferably, the compound is cypermethrin which has a ratio of cis:trans isomers in the range 40 to 50 60 to typically 47:53.

The formulation -pf:gfrabl also has a spreading agent in the form of a silicone oil which itself must be soluble in the j* 5 paraffinic oil. This, it has been found, allows for more effective and rapid spreading of the formulation over the skin S.Q of the cat~te to which it has been applied. The silicone oil ,S prefe-r ly zhld bo present in the formulation in an amount of at least 5% by mass, preferably 5 to 20% by mass. Examples of suitable silicone oils are polydimethyl cyclosiloxanes such as those *sold by Dow Corning under the designation Dow Corning 344 and 345: m oo.

A>7 6- DOW CORNING 344 FLUID (TETRAMER) CH 3 CH3 Si z N Si *Si 0 00 *0 0 0 0 0 0 0 0 CH 3 CH3 DOW CORNING 345 FLUID (PENTAMER)

V

0 0*0 00000.

0 0 00 0 0 0 00

CH

CH3 Si 0 CH 3 '3 I CHM Si

S

CH 3 CH 3 Si

C

P

a -7- It must be noted that the related straight chain methyl siloxanes such as that sold by Dow Corning under No. 200 are not soluble in paraffinic oils and are ineffective in the practice of the invention. Dow Corning 200 fluid has the formula:

S

ii

I

S

S

*5

''I

-3 CH

CH

3 Si 0 Si CH

C

3

CH

3 The above-mentioned South African Patent 81/5273 while suggesting the use of silicone oils in general contains no disclosure of any specific silicone oil, nor any teaching or suggestion that such silicone oil must be soluble in a liquid paraffinic oil in order to produce an effective pour-on formulation for cattle. Further, there is r- disclosure or teaching in that patent to the effect that when a liquid paraffin oil is used in conjunction with a pyrethroid of formula that the liquid paraffin oil must have a very low aromatics content.

The invention will be illustrated by the following examples.

EXAMPLE 1 A pour-on formulation for cattle contained the following ingredients: I .2 i -8- Ingredient Cypermethrin Whiterex 309 Amount (g/e) 11,1 g 830,5 g

S

*r S 6@ *6 6* The cypermethrin contained 90% Cypermethrin and 10% related reaction products. The cis:trans isomer ratio was 47:53.

Whiterex 309 is a paraffinic oil containing no detectable aromatics by clay gel analysis.

The formulation was produced by simply blending the molten cypermethrin into the paraffinic oil and removing any insolubles by filtration.

This formulation was subjected to a number of field trials to evaluate its efficacy in controlling a range of ticks on cattle. The formulation proved to be both efficacious and safe in all these trials. One such trial will now be described: 1. AIM: This trial was carried out to determine the efficacy of a pouron formulation (Trial formulation Cypermethrin 1% m/v) on natural tick infestation on cattle in the district of Magudu, Zululand.

All trial animals were examined for any signs of irritation or hairloss.

S

05 9 S S r

I

1-cl- -9- 2. TRIAL FORMULATION: The following formulations were used during the course of the trial: 2.1 Trial formulation Pour-on formulation as in Example 1.

2.2 Drastic Deadline (Bayer) Pour-on remedy with flumethrin 1% m/v as active ingredient.

4ib l TRIAL PREMISES: The trial was carried out on the farm Sterland of Mr RS van Heerden in the district of Magudu, Zululand.

The following tick species were present in large numbers: Rhipicephalus evertsi evertsi Red legged tick Amblyomma hebraeum Bont tick Hyalomma species Bont legged tick *Boophilus decoloratus (Blue tick) were present in limited numbers.

4. TRIAL ANIMALS: Fifteen Brahman crossbred cattle of both sexes were used in the trial. The body mass of the animals varied from 430 600kg.

Trial animals were divided at random according to tick counts into different groups: Trial formulation Drastic Deadline Control Group r ia i 10 TRIAL PERIOD: The trial commenced on 14 April 1987 and was concluded on 16 June 1987.

09 S 800 0 9 9 .9 6. TRIAL PROCEDURE: 6.1 The trial animals were individually marked and allocated to one of three groups according to tick counts: Group 1 Trial formulation at 1 ml/10 kg body mass Group 2 Drastic Deadline at 1 ml/10 kg body mass Group 3 Because of high tick counts the control group was sprayed with an organophosphate on day 1 and were thereafter left untreated.

6.2 The trial was visited weekly and a complete tick count was done. All the trial animals were examined carefully for any sign of irritation or loss of hair.

6.2 The three groups were placed in seperate camps.

6.4 The control group was exchanged during the trial with similar animals to prevent harm because of the high number of ticks.

The remainder of the animals on the farm were dipped with an organophosphate.

i I. i 11 7. RESULTS: GROUP DAY TOTAL TICK NUMBERS PER GROUP A. hebraeum R.e.evertsi Hyalomma spp.

P H V P H V P H V

FORMULATION

DEADLINE

CONTROL

FORMULATION

DEADLINE

CONTROL

FORMULATION

DEADLINE

CONTROL

FORMULATION

DEADLINE

CONTROL

FORMULATION

DEADLINE

CONTROL

O 185 14 157 13 167 16 173 8 167 151 6 7 41 22 39 14 68 21 13 28 29 16 0 ::a 400* a t a.

040 "to:a @0 0 a a

FORMULATION

DEADLINE

CONTROL

FORMULATION

DEADLINE

CONTROL

FORMULATION

DEADLINE

CONTROL

35 18 0 0 0 58 1 42 12 9 76 49 12 81 P male and female unengorged A. hebraeum.

H half engorged female A. hebraeum.

V fully engorged female A. hebraeum.

The significance of P, H and V lie in the time the ticks have spent on the animal and thus in the efficacy of the dip used.

REMARKS:

B. decoloratus ticks were only present in a limited number on control animals.

There was no signs of irritation or loss of hair during the course of the trial.

12 12 8. CONCLUSION The trial formulation gave excellent control of natural tick infestations in the district of Magudu, Zululand after weekly treatments. It seems from above-mentioned results that trial formulation has a definite repellent effect on ticks. No sign of irritation or loss of hair was encountered during the trial.

To improve the spreading properties of the formulation, it was decided to investigate the addition of various spreading agents. A variety of silicone oils were tried ranging from such oils having a water-like consistency to those having a Le high viscosity. It was found that straight chain siloxanes such as hexamethyldisiloxane were not suitable. Suitable silicone oils were found to be those which were soluble in the paraffinic oil. Particularly useful silicone oils were found to be Dow Corning 344 and 345, described above. An improved formulation (Example 2) was produced containing the following ingredients.

Ingredient Amount g/e Cypermethrin 11,1 g Dow-Corning 344 95,5 g Whiterex 309 745,0 g The cypermethrin was 90% technical as used in the first example, and the Whiterex 309 was also the same as that used in Example 1. The formulation was produced by blending the molten cypermethrin into the paraffinic oil whereafter the Dow-Corning 344 was stirred into the blend until it was homogeneous.

i 13 Foreign material was removed by filtration.

This formulation was also subjected to a wide range of field trials to evaluate its efficacy in the control of ticks on cattle. This formulation was found to spread more effectively and quicker than the formulation of Example 1. Again, a wide variety of ticks could be controlled using this formulation.

One such trial will now be described: 1. AIM To determine the efficacy of the formulation of Example 2 against natural infestation of adult ticks in the field.

SThe formulation was compared with the formulation of Example 1.

r i 2. TRIAL FORMULATION 2.1 Formulation of Example 1.

.0 6 2.2 Formulation of Example 2.

2.3 No controls were used.

3. TRIAL PREMISES: The trial was conducted on the farm of Mr CJ Bezuidenhout in the Groblersdal district. Facilities consisted only of a rudimentary kraal and pressure run.

4. TRIAL PERIOD: The trial was carried out on 9 November 1988 and terminated on 23 November 1988 when satisfactory control of the adult tick population was demonstrated.

L

CT

EaYI~YIW-VY1*E~9XF*P*I I r 14 TRIAL ANIMALS: The cattle involved were of an Afrikaner/Brahman cross-breed, of all shapes and sizes, including at least 2 bulls.

6. TRIAL PROCEDI)URE: 6.1 Ten tagged animals were selected at random and tick numbers of the various species were obtained.

6.2 The larger group of selected animals were treated with the trial formulation of Example 2.

6.3 The smaller group of selected animals were treated with formulation of Example 1.

S

S

0 S. S

S

0 6.4 The following tick species were encountered in large numbers: 6.4.1 Amblyomma Hebraeum Bont tick 6.5 The following tick species were encountered singly on occasion: 6.5.1 Rhipicephalus evertsi -'Red-legged tick

SSSOS.

0

S.

I

S 55 6.5.2 Hyalomma spp. Bont-legged tick 6.5.3 Rhipicephalus appendiculatus Brown ear tick 2 15 7. RESULTS:

FORMU-

LATION

DATE TICK SPECIES A 1- I n 4-V Example 2

S..

30

S

S.

SW

5*

S

S

S. S S 9/11 16/11 23/11 9/11 16/11 23/11 I *U IIJJL aU uIi L1L~.l LJ.

P H V 152 24 1 R.appendiculatus Hyalomma spp.

Hyalomma. spp.

Example 1 Hyalomma spp.

P male and female unengorged A. hebraeum.

H half engorged female A. hebraeum.

V fully engorged female A. hebraeum.

The significance of P, H and V lie in the time the ticks have spent on the animal and thus in the efficacy of the dip used.

8. CONCLUSIONS The efficacy of both formulations was clearly established with no toxic symptoms being observed and no sign of skin irritation or loss of hair was observed.

A liquid pour-on formulation of the invention was subjected to trials to establish its efficacy in controlling sucking lice, biting lice and nuisance flies on cattle. The nature of the trials and the. 'results obtained are set out hereinafter in Trials A and B.

II I 16 TRIAL A 1. AIM: This tria. was carried out to determine the efficacy of trial formulation A351 (Cypermethrin 1% m/v) at a dosage rate of lml/lOkg body mass on sucking lice (Lignognathus vituli) and biting lice (Damalinia bovis) on cattle.

i 2. TRIAL FORMULATION: 2.1 Active 0 09 0 9 00 0 0 0 4 9*9* *4 *9*9 9 Trial formulation A351 contains Cypermethrin 1% m/v with a purity degree of 90,0% and a 50:50 ratio of a cis and trans isomers.

2.2 Base The active ingredient is dissolved in a paraffin oil base (Whiterex 309) which acts as carrier.

3. TRIAL PREMISES: The trial was carried out on the following premises: 3.1 Owner: 3.2 Farm: Mnr PJ Holtzhausen Venterspoort 3.3 District: Griekwastad 4. TRIAL ANIMALS: The following animals were used in the trial: 4.1 Breed: 4.2 Age: 4.3 Number: 4.4 Sex: Afrikaners 3 months 6 years 41 Cows with calves 4cb i- I A 1 f 17 The condition of the cattle varied from fair to very bad. Differing degrees of lice infestation were present on the shoulders, neck, pectoral area, dewlap, escutcheon and root of the tail. Some of the animals had crust formation of exudate surrounding the root of the tail.

TRIAL PROCEDURE: 5.1 Complete macro and microscopic examinations were carried out on the trial animals. L. vituli and D. bovis infestation was diagnosed.

5.2 Thirteen animals with the highest lice infestation were individually marked with ear tags.

5.3 The animals were divided as follows: Us r Eight animals Five animals Trial formulation A351 Control

S.O.S.

0

S

5.4 Trial formulation A351 was applied at a dosage rate of 1 ml/lOkg body mass, on the back from the base of the skull to the root of the tail.

5.5 The treatment was repeated after 1.4 days.

5.6 The remainder of the cattle in the herd were also treated with trial formulation A351.

A minimum dosage of 20 ml were used on animals lighter than 200kg.

5.7 The treated and control groups were separated during the course of the trial.

5.8 Complete macro and microscopic examinations for the presence of lice on the cattle were made on day 0, 14 and 42.

5.9 The untagged cattle were also examined on day 42 for the presence of any lice.

T -7 I 1-~ Il 18 6. RESULTS: 6.1 L. vituli The following results were obtained: 4* 0 9 *99 9.

*9 9 9999 9..

9 GROUP DEGREE OF INFESTATION DAY 0 DAY 14 DAY 42 A351 Cattle 3 0 Cattle 8 0 Cattle 9 0 0 Cattle 28 0 0 Cattle 29 0 Cattle 30 0 0 Cattle 36 0 0 Cattle 41 0 0 Control 24 38 1 2 5 6.2 D. bovis: GROUP DEGREE OF INFESTATION DAY 0 DAY 14 DAY 42 A351 3 0 9 0 28 0 0 30 0 36 0 41 0 0 Control 24 2 5 0 Negative Light infestation Medium infestation Heavy infestation Macro and microscopic examinations were carreid out on the remainder of the herd on day 42 and no sign of lice were found. Crusts and exudate had also reduced and the general condition of all the cattle had improved.

I

*S

S

S. S S S eS Sc 19 8. CONCLUSION Mixed lice infestation (sucking and biting) on cattle were killed by two treatments of trial formulation A351 with an interval of 14 days at a dosage rate of Iml/10kg body mass.

TRIAL B 1. AIM: This trial was carried out to determine the efficacy of Trial formulation A351 (Cypermethrin 1% m/v) as a pour-on formulation at a dosage rate of lml/10 kg body mass on the nuisance fly M. domestica on cattle.

2. TRIAL FORMULATION: 2.1 Active Trial formulation A351 contains 1% Cypermethrin with a purity degree of 90,0% and a 50:50 ratio of a cis and trans isomers.

2.2 Base The active ingredient is dissolved in a paraffin oil base (Whiterex 309) which acts as carrier.

3. TRIAL PREMISES: The trial was conducted on the following premises: 3.1 Owner: 3.2 Farm: Mr Bill Thwaite Edanvales

S

55 S S 3.3 District: Krugersdorp 4. TRIAL ANIMALS: The following animals were used in the trial: 4.1 Breed: 4.2 Age: 4.3 Sex: 4.4 Number: Friesland 3 6 years Female

__I

I

L

1 20 TRIAL PROCEDURE: 5.1 The premises was visited, flies were caught and a diagnosis was made of M. domestica.

This diagnosis was verified by Dr Nevill, Department Entomology at Onderstepoort.

All the animals had clear signs of fly irritation (excessive tail movements, lashing of ears, swinging of the head and knocking of feet).

5.2 The trial animals grazed in two groups in different parts of the farm.

Group 1 40 Lactating cows Group 2 35 Dry crws and calves 5.3 Fly counts were made as follows on all the animals in both groups: 9 o o 9 9* Day 1 15 Day 16 46 daily (excluding Saturdays and Sundays) Three times a week 5.4 Fly counts were made at the time of day when highest fly activity was expected.

The total number of flies on the head, one side and feet were counted and the average calculated.

5.6 Wind and temperature changes were noted.

5.7 All the animals were treated on day 8, 15, 21, 28 and 42 with trial formulation A351 at a dosage rate of 1 ml/10 kg. The product was applied from the base of the skull to the base of the tail.

5.8 The animals in Group 1 were fed in the camp and those in Group 2 daily grazed for a short period on cultivated pastures.

*09999 9 0* 0 9 *r 99 21 6. RESULTS:

V

V

S.

S 0@

S.

S

*5* @0 0

S*

00 0 0 0 50 0 0 00 *5 0 0 9* *00 0 000000 0. 0 0 0 00 The animals in the treated group became more restful during the course of the trial but the animals in the control group showed no sign of change. The following number of flies was found: WEATHER DAY AVERAGE NUMBER SUN- CLOUD TEMPERATURE WIND FLIES PER ANIMAL SHINE SEMI COVER 15- 21- LIGHT STRONG CONTROL A351 1 47 53 2 43 48 3 50 57 4 33 5 45 51 8* 55 51 9 49 33 +I 10 54 18 11 45 24 +F 12 37 15* 57 17 45 7 +F 19 54 4 21* 41 +F 23 45 3 24 47 4 26 40 3 +F 28* 49 30 53 4 32 50 2 34 49 3 36 54 38 46 12 40 47 18 42* 46 29 44 53 9 -F 46 50 3 Treated with trial formulation A351 L S q 1 I CI 22 8. CONCLUSION Weekly treatment with trial formulation A351 at a dosage rate of Iml/lOkg body mass causes a reduction in nuisance fly M. domestica on cattle. The animals in the treated group were notably more restful than the untreated animals t

,I

i^ et 0 0 e 0* 0• 0 00 0 0 ft ft ftftftf ft ft

Claims (10)

1. A liquid pour-on formulation for use in the control of lice, nuisance flies and ticks on cattle comprising 0,1 to 2 percent by weight of a compound of the formula I: CI\ CN CHI C=CH CO.OCH O CI CH 3 CH I!k 0 0 *00* 00 0 @000 0 000* *0 0 00 0 0 @0 dissolved in a liquid paraffinic oil containing less than 1 percent aromatics by weight and further including a silicone oil which is soluble in the paraffinic oil.

2. A formulation according to claim 1 wherein the paraffinic oil contains no aromatics.

3. A formulation according to claim 1 or claim 2 wherein the compound is cypermethrin which has a ratio of cis:trans isomers in the range 40 to 50:60 to

4. A formulation according to claim 1 or claim 2 wherein the compound is cypermethrin which has a ratio of cis:trans isomers of 47:53. *0 0 S@ S 0* S ~0 *S S 0 SS 55 S S 9 5005 S S A formulation according to claim 1 wherein the silicone oil is a polydimethyl cyclosiloxane.

6. A formulation according to claim 5 wherein the polydimethyl cyclosiloxane has the formula: CH, CH S3 CH 3 C3 Si Si 1 H CH C '0 0 C3 CH3 _I >7 25

7. A formulation according to claim 5 wherein the polydimethyl cyclosiloxane has the formula: CH 3 CH 3 0 >Si CH 3 0 Si 0 CH3 3 Si i CH 3 0 I Si Si CH Si H 3 3 CH, CH,

8. A formulation according to any one of claims 5 to 7 wherein the silicone oil is present in the formulation in an amount of at least 5 percent by mass.

9. A formulation according to any one of claims 5 to 7 wherein the silicone oil is present in the formulation in an amount of 5 to percent by mass. A pour-on formulation according to claim 1 and substantially as herein described with reference to each of the examples. 26

11. A method of controlling lice, nuisance flies and ticks on cattle including the steps of applying a formulation according to any one of the preceding claims on to the skin of cattle.

12. A method according to Claim 11 substantially as hereinbefore described with reference to any one of the examples. S. DATED: 3 June 1991 PHILLIPS ORMONDE FITZPATRICK Attorneys For: SENTRACHEM LIMITED (0070h) i 1 I i| i J