AU651990B2 - Pesticidal products - Google Patents

Description

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r i ii OPI DATE 17/03/92 AOJP DATE 30/04/92 INTERNAl APPLN. ID 83384 91 PCT NUMBER PCT/AU91/00360 .REATY (PCT) (51) International Patent Classification 5 (11) International Publication Number: WO 92/03048 A01N 25/32 Al (43) Internrticil Publication Date: 5 March 1992 (05.03.92) (21) International Application Number: PCT/AU91/00360 (74) Agents: CORBETT, Terence, Guy et al.; Davies Collison, 1 Little Collins Street, Melbourne, VIC 3000 (AU).

(22) International Filing Date: 13 August 1991 (13.08.91) (81) Designated States: AT, AT (European patent), AU, BB, BE Priority data: (European patent), BF (0API patent), BG, BJ (OAPI PK 1700 13 August 1990 (13.08.90) AU patent), BR, CA, CF (OAPI patent), CG (OAPI patent), CH, CH (European patent), CI (OAPI patent), CM (71) Applicants (for all designated States except US): COMMON- (OAPI patent), CS, DE, DE (European patent), DK, WEALTH SCIENTIFIC AND INDUSTRIAL RE- DK (European patent), ES, ES (European patent), FI, SEARCH ORGANISATION [AU/AU]; Limestone FR (European patent), GA (OAPI patent), GB, GB (Eu- Avenue, Campbell, ACT 2601 CIBA-GEIGY ropean patent), GN (OAPI patent), GR (European pa- AUSTRALIA LIMITED [AU/AU]; 140 Bungaree tent), HU, IT (European patent), JP, KP, KR, LK, LU, Road, Pendle Hill, NSW 2145 LU (European patent), MC, MG, ML (OAPI patent), MR (OAPI patent), MW, NL, NL (European patent), (72) Inventor; and NO, PL, RO, SD, SE, SE (European patent), SN (OAPI Inventor/Applicant (for US only) HARRINGTON, Kevin, patent), SU+,TD (OAPI patent), TG (OAPI patent), US.

James [AU/AU]; 34 Chesterville Drive, East Bentleigh, VIC 3165 Published With international search report.

(54)Title: PESTICIDAL PRODUCTS

MORTALITY

100- 0-(57) Abstract (57) Abstract

MONOCROTOFOS

4 h INSTAR LARVAE NUVACRON CONTROL J4-2 200 100 50 25 125 6-25 CONCENTRATION OF AI (ppm) A pesticidal matenal which comprises an inclusion compound or molecular complex of a pesticide and a host molecule characterised in that the host molecule is a mono-, oligo- or polysaccharide ester. A pesticidal composition and a method for combatting insect pests involving the above pesticidal material are also described.

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WO 92/03048 PCT/AU91/00360 PESTICIDAL PRODUCTS This invention relates to new forms of pesticidal products and methods for their manufacture.

Environmental awareness of the dangers of pollution arising from the widespread application of chemical pesticides, as well as the increased cost of developing and registering new pesticides, has stimulated interest in developing formulations that will improve the effectiveness of present pest control agents by, for example, improving their shelf life and increasing their stability and longevity of action in the field. There is also a need to minimise the health and environmental hazards associated with the use of common pesticides such as organophosphates and toxic metallic compounds.

WO 92/03048 PCT/AU91/00360 -2 Typical formulations used to apply known pesticides include dusts and sprays. Dusts are often used to control termites, cockroaches, lepidopterous larvae, grain insects, ants and other urban and rural pests. Sprays, which include emulsions and wettable powders, are extensively employed in combat;- agricultural crop insect pests of cotton, grain, rice, sugar, tobacco, vegetables and fruits as well as wood destroying insects such as termites and wood borers. However, the effectiveness of many pesticide applications is often markedly reduced by factors such as loss of the active ingredient by evaporation, its hydrolysis or inactivation in the presence of moisture or when in contact with soil, and degradation of the pesticide through the action of light. This lack of persistence may make repeated applications essential to ensure continued and adequate pest control.

A further problem in the control of insect pests is that insects can often detect the toxic agents used to the extent that they are repelled and avoid ingesting or coming into contact with the toxicant.

For many years pest control operators in Australia have used arsenic trioxide to eradicate Lermite infestations in and around buildings. The arsenical compound is normally puffed into the galleries created by the termites in infested wood, causing the toxic dust to adhere to the termites' cuticle and appendages such an antennae, legs and hair. This very effective method exploits the insects' behavioural characteristics of social grooming and dead termite control. During the grooming ritual, traces of toxic dust may be ingested by the grooming insect, which will eventually die. Dead termites are eaten by survivors who themselves soon become victims, thus aiding in the translocation of the poison throughout the colony.

However, the distribution of arsenical compounds having a wide spectrum of insecticidal and mammalian toxicity is undesirable, and the alleged carcinogenicity of arsenic, particularly in its trivalent oxidised state, has resulted in a ban on its use for termite eradication in the U.S.A. Similar i L~ 1- WO 92/03048 PCT/A U91/00360 3 restrictions may be imposed in Australia and other countries. Alternative termiticidal dusts have been proposed that rely upon adsorbing known insecticides such as organochlorins, organophosphates or synthetic pyrethroids on finely divided supports such as kaolin or talc. Such insecticidal dusts still present a considerable hazard to the pest control operator as, in most cases, the adsorbed insecticide has a measurable vapour pressure and may be adsorbed through skin contact or inhalation. Moreover, these dusts have generally been found to repel the termites, which seal off the dusted areas to avoid contact with the poison.

There have been many attempts to achieve safer and more effective use of pesticides by developing controlled release systems to allow reduced rates and frequency of application and to minimise evaporation and degradation losses. One such approach is disclosed in Australian Patent Application No.

83/13398 in which biologically active materials are trapped as discontinuous domains within a continuous insoluble matrix gel, the biodegradation of which results in slow release of the active agent. A disadvantage of this method is the difficulty of obtaining complete encapsulation in products that are sufficiently finely divided for dusting applications.

Another known method of stabilising pesticides is to form molecular complexes of the clathrate or inclusion type between the "guest" pesticide and a "host" lattice. Inclusion in organic hosts results in many modifications to the properties of the guest compounds such as fixation of volatile materials, masking of odorous compounds, stabilisation against hydrolysis, protection against oxidation and photolysis, e.g. by ultraviolet light, and the modification of their physical and biological properties.

U.K. Patent No. 1,453,801 discloses the formation of a molecular complex of the clathrate type between the general purpose organophosphate insecticide dichlorvos (DDVP) and cyclodextrins, particularly p-cyclodextrin to provide a stable formulation with powerful insecticidal effects.

i c WO 92/03048 PCT/AU91/00360 -4- Similar complexes have been described between CD and methyl parathion, another organophosphate insecticide, as well as with a range of natural and synthetic pyrethroids.

Dichlorvos (DDVP) is an inexpensive, readily available but volatile and inflammable insecticide. It is also susceptible to rapid hydrolysis by alkali and water and so is devoid of long lasting effects. The DDVP-CD complex, containing 14-16% DDVP based on the mass of p-cyclodextrin, has very low volatility and reacts but slowly with moist air. However, its application to insect control is justified only under dry conditions; if the water-soluble p-cyclodextrin were to dissolve the complex would dissociate with concomitant rapid hydrolysis of the DDVP.

Cyclodextrin complexes of natural pyrethrins and synthetic pyrethroids, containing 6-15% of the toxicants, showed enhanced photostability over the free insecticides which are rapidly degraded in air and light. Persistency of the pyrethroids was enhanced at the expense of some loss in contact insecticidal activity, but the complexes retained their insecticidal activity upon ingestion by insects.

In summary, cyclodextrin-included insecticides are limited in use by cost and low persistency in wet conditions, their application being justifiable only in certain areas. It is an object of this invention to provide inclusion compounds or molecular complexes of the type in question in which one or both, of the above-described disadvantages is minimised or at least reduced.

We have now found that derivatives of other types of polyhydroxylic compounds are also capable of forming inclusion compounds or molecular complexes with pesticides.

In accordance with the present invention there is provided a pesticidal material which comprises an inclusion compound or molecular complex of a ~1 WO 92/03048 PCT/AU91/00360 mono-, oligo- or poly-saccharide ester and a pesticide.

Any suitable known mono-, oligo- or poly-saccharide may be used as the basis of the mono-, oligo- or poly-saccharide ester, for example, glucose and sucrose.

The preferred mono-, oligo- or poly-saccharide esters are mono-, oligo- B or poly-saccharides esterified by carboxylic acids. The carboxylic acids may be mono-, di- or poly-basic, and may be a simple aliphatic or alicyclic carboxylic acid, of suitable carbon chain length, for example fatty acids, such as palmitic acid, or may contain various substituents including hydroxyl groups. Esters of optionally substituted aromatic carboxylic acids are also particularly suitable.

The mono-, oligo- or poly- saccharide ester may contain any number of ester groups up to the maximum permitted by the number of (esterifiable) hydroxy groups available. Preferably the maximum number of hydroxy groups is esterified.

Examples of suitable compounds are: p-D-Glucose (penta) myristate; Mannitol (hexa) palmitate; Pentraerythritol (tetra) palmitate; p-D-Glucose (penta) palmitate; Pentaerythritol (tetra) monosuccinate; IPentaerythritol (tetra) benzoate; Sucrose (octa) benzoate; Mannitol (hexa) benzoate; 3-D-Glucose (penta) cyclohexane carboxylate; Pentaerythritol (tetra) phenylacetate; Pentaerythritol (tetra) cyclohexane carboxylate; or Mannitol (hexa) cyclohexane carboxylate.

WO 92/03048 PCT/AU91/00360 -6- Sucrose benzoate is particularly preferred.

Preferably, the inclusion compounds or molecular complexes are substantially water insoluble. Thus, it will be appreciated that the nature of the acid moiety and the degree of esterification of the mono-, oligo- or poly-saccharide will govern the solubility of the inclusion compound or molecular complex produced.

Pesticides from any of the known classes can be considered for use in accordance with this invention, provided that their molecular dimensions are such as to permit inclusion into or complexing with the mono-, or oligo- or poly-saccharide ester.

Suitable pesticides include the pyrethroid, organophosphorus and carbamate pesticides. Some suitable pesticides identified by their common names as given in "The Pesticides Manual", 7th Edition, 19S3 and published by the British Crop Protection Society, include the organophosphates chlorpyrifos, dichlorvos, fenthion, fenthion ethyl, fenitrothion, fonofos, methacriphos, methomyl, monocrotofos, phoxim, and trithion, and the synthetic pyrethroids fenvalerate, permethrin and cypermethrin.

Whilst the present invention is generally described herein with reference to compounds or complexes which involve pesticide guests, the invention is not restricted to such guests. Any other guest substance may be considered for applications outside the field of insect and other pest control.

The basis and practice of the invention are further described and illustrated by the following non-limiting examples.

WO 92/03048 PCT/AU91/00360 -7- EXAMPLE 1 Preparation of Sucrose octa (Benzoate) Sucrose (12.5g, 0.037 mol) was suspended in pyridine (125 mL) and i benzoyl chloride (43 ml, 0.37 mol) was added slowly with stirring. The Sreaction mixture was then heated to reflux temperature for 1 hour and then allowed to return to room temperature. Aqueous NaHCO 3 was added (430 mL, and the mixture was cooled in an ice bath to produce a gummy yellow solid. After decantation, the solid was washed several times with cold water and finally crystallised from dilute ethanol to give the product m.p. 85-87 OC.

Yield 6.2g, 14% TLC (Chloroform) Rf 0.6 IR (Nujol) 1710 cm EXAMPLE 2 Preparation of an inclusion compound sucrose benzoate and monocrotofos.

Sucrose benzoate (20g) is heated to about 110 C to give a mobile S 20 molten phase. Monocrotofos (technical grade) 5g (equivalent to 4g pure) is i added and the resultant molten mixture (which is very mobile at this temperature) is stirred vigorously for several minutes to ensure effective mixing of the two components, which appear miscible under these conditions.

Agitation is stopped and the molten mixture is allowed to cool to room temperature. The resultant solid mass is ground to pass 50 micron screen and is washed several times with either water or cold ethanol to remove excess monocrotofos monocrotofos which is not formally included, but rather which is merely adhering to the outside surfaces of the host particles). The final product, after drying in air at room temperature, is typically a cream coloured, free flowing powder, with a mean particle diameter of about microns, water insoluble and with monocrotofos content of about 13% (pure.

basis).

i i WO 92/03048 PCT/AU91/00360 -8- This material may then fe formulated to enable it to be sprayed in an aqueous medium.

EXAMPLE 3 Preparation of an indusion compound of glucose penta-palmitate and monorotofos.

Glucose penta-palmitate (20 g) and monocrotofos (5g) are treated as described in Example 2. The final product, after washing with either water or cold ethanol, is an off-white, free flowing powder, with similar particle size as the product described in Example 10. The final product contains about 4% monocrotofos.

EXAMPLE 4 Bioactivity of the inclusion compound of sucrose benzoate and monocrotofos.

The compound produced according to Example 2 is formulated by the addition of wetting agents, detergents and other emulsifying agents so that it forms a stable suspension, effectively dispersed in water. Leaves of cotton, soya and tomato plants are sprayed to run-off or dipped in suspensions of the above at concentrations (of active ingredient) of 200, 100, 50, 25, 12, 6, 3, and 0.8 ppm.

On drying in air, the leaves are infested in separate biassays with larvae of Heliothis armigera in both the first instar (neonate) and 4th instar stages of i development.

-Vi The infested leaves are closed (but not hermetically sealed) in small clear plastic vials and held in a controlled environment (23 50% relative humidity) with normal diurnal variations of light and darkness. Mortality was assessed after 5 days for the first instar larvae and after 3 days for the fourth instar larvae.

I 'I--Y--~LII~III~ WO 92/03048 PCT/AU91/00360 -9- The mortality rates are shown in Figures 1 and 2 which show a plot of mortality rate against the concentration (ppm) of the active ingredient (AI) for the first instar (neonate) larvae (Figure 1) and the fourth instar larvae (Figure 2).

EXAMPLE Preparation of Mannitol hera (Palmitate) Mannitol (5.46 g, 0.03mol) was suspended in pyridine (40mL) and chloroform (5mL) in an ice bath. Palmitoyl chloride (57.8g, 0.21mol) was added slowly with stirring. The precipitated solid was filtered, dissolved in chloroform and washed several times with water. The organic layer was dried over anhydrous NaSO 4 and the solvent removed under reduced pressure to give a viscous orange syrup which was crystallised from chloroform/methanol.

Recrystallisation from the same solvent mixture gave the product m.p. 59-61 C (Lit.64 Yield 19g, TLC (Chloroform) single spot Rf 0.8 IR (Nujol) 1740cm' EXAMPLES 6 to The indicated compounds were each prepared by a method similar to that described in Example 1, from the appropriate sugar and acid anhydride.

EXAMPLE 6 p-D-Glucose penta (Cydohexane Carbox)yate) mp 174-176 C. Yield 6.7g, 67%. TLC (90 Chloroform/10 Hexane) Rf IR (Nujol) 1738 cm 1 L~ i 1 rl I t. WO 92/03048 PCT/A U91/00360 EXAMPLE 7 PentaeiydIuicJ Lera (Phent) aet e) Coarse colourless needles, mp 72 0 C. Yield 7.8g, 64%. TLC (9"1 CHCl 3 /3 MeOH) Rf 0.6. IR (Nujol) 1730 cm".

EXAMPLE 8 Pentaeyhri1 letr (Phenrpropionate) Fine long needles mp 49-51 Yield 2.5gm, 37%. TLC (97 CHCI 3 /3 MeOH) Rf 0.75. IR (Melt) 1730 cmf 1 EXAPLE 9 Pentaeayhrit1 C.dohexanecarbaiate mp (MeOH/CHCI 3 111 0 C, TLC (CHCI 3 Rf 0.7. IR 1735cm'.

EXAMPLE Manritci hexw(Cydohexane Catxlate) mp 135-140 0 C. Yield 3.24g, 435%0. TLC (50 MeOH/50 CHCI) gave a single spot Rf O.S. IR (Nujol) 1735 cm'.

EXAMPLE 11 Preparation o Addus Adducts of the compounds of Examples 5 to 10 with the active ingredients monocrotophos and methacrifos were prepared by one of two methods: -i I t ~p- WO 92/03048 PCT/AU91/00360 Crystallisation, whereby the host and guest were dissolved in a suitable solvent, and the solvent removed slowly under reduced pressure at a moderate temperature (ca. 50 Effective mixing was maintained during this procedure.

Fusion, involving mixing of the solid host with the solid guest and the melting of the resulting composite. The molten mixture was stirred vigorously to promote homogeneity and allowed to cool at room temperature. The resulting solidified mass was ground up.

In each case, the solid products were collected and washed with water (in the case of monocrotophos) and with 80% aqueous methanol (in the case of methacrifos) to remove any active ingredient adhering to the outside surfaces of the adducts.

The content of active ingredient was determined using HPLC methods for monocrotophos and GLC methods for methacrifos.

EXAMPLE 12 Biological Eficacy of Adducs The biological efficacy of adducts prepared according to Example 11 was determined as follows: Freshly-picked cotton leaves were dusted with the adduct, which had been ground to pass a 50 micron screen. The bioassay was conducted using larvae of Heliothis armigera (4th instar).

For the purposes of evaluation, it was assumed that the distribution of adduct over the surface of the leaf was uniform, although this was clearly an approximation. Larvae were selected to be of similar size and weight (30-40 mg) and the leaf area was constant (10cm 2 It was assumed that the L -4 WO 92/03048 PCT/A U91/00360 12 amount of leaf eaten by the larvae was a direct measure of the amount of active ingredient ingested.

Results obtained for the adducts thus assayed are summarised in Table 1.

Notwithstanding the fact that the uneven coverage of the leaf by the adduct prevents more precise interpretation of the data, some interesting observations can be made.

.0 In several cases, insect mortality was maximum even when little or no eating was observed. This mortality was seen to occur very quickly, suggesting poisoning of the larvae by contact.

i ii WO 92/03048 PCT/AU91/00360 13 TABLE 1 (see Key to Headings Below) ExamDle (6) 1 cryst. mono 0.338 30 0.102 cryst. methac 0.576 <1 0.006 100 cryst. mono 0.019 30 0.006 6 cryst. mono 0.013 5 0.0006 100 cryst. methac 0.296 <1 0.003 100 7 cryst. mono 0.014 5 0.0007 100 8 cryst. mono 0.017 20 0.003 cryst. methac 0.198 2 0.006 100 9 fusion mono 0.018 <1 0.0002 100 fusion methac 0.021 <1 0.001 100 10 fusion mono 0.087 <1 0.0009 100 fusion methac 0.082 20 0.016 Key to Table Headings (1) (2) (3) (4) (6) Method of forming adduct. cryst. crystallisation Active ingredient. mono= monocrotophos; methac methacrifos Quantity of active ingredient applied of body weight) Leaf consumed Quantity of active ingredient presumed ingested of body weight) Mortality

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i- 1 L )cl 13a Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

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Claims (8)

1. A pesticidal material which comprises an inclusion compound or molecular complex of a pesticide and a host molecule, characterised in that the host molecule is a mono-, oligo- or poly-saccharide ester.

2. A pesticidal material as claimed in Claim 1, characterised in that the I host molecule is a carboxylic ester of a mono-, oligo- or poly-saccharide. j 10

3. A pesticidal material as claimed in Claim 1 or Claim 2, characterised in that the host molecule is p-D-Glucose (penta) myristate; Mannitol (hexa) palmitate; Pentraerythritol (tetra) palmitate; p-D-Glucose (penta) palmitate; Pentaerythritol (tetra) monosuccinate; Pentaerythritol (tetra) benzoate; Sucrose (octa) benzoate; Mannitol (hexa) benzoate; p-D-Glucose (penta) cyclohexane carboxylate; Pentaerythritol (tetra) phenylacetate; Pentaerythritol (tetra) cyclohexane carboxylate; or Mannitol (hexa) cyclohexane carboxylate.

4. A pesticidal material as claimed in Claim 1, characterised in that the host molecule is a sucrose benzoate. A pesticidal material as claimed in any one of the preceding claims, characterised in that the pesticide is chlorpyrifos, dichlorvos, fenthion, fenthion ethyl, fenitrothion, fonofos, methacriphos, methomyl, monocrotofos, phoxim, trithion, fenvalerate, permethrin or cypermethrin.

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6. A pesticidal composition, characterised in that it comprises as an active ingredient a pesticidal material as claimed in any one of the preceding claims.

7. A method for combating insect pests, characterised in that a pesticidal material or composition as claimed in any one of Claims 1 to 6 is applied to the insects or their locus.

8. Pesticidal materials, pesticidal compositions containing them or methods of combating insect pests involving them, substantially as hereinbefore described with reference to the Examples and/or drawings. DATED this 6th day of June. 1994 Commonwealth Scientific and Industrial Research Organisation By Its Patent Attorneys DAVIES COLLISON CAVE L l40603.n-'orrdah.3384 sc. c