WO2016111661A1

WO2016111661A1 - Capsule formulation technique for insect growth regulator pyriproxyfen, a juvenile hormone analog

Info

Publication number: WO2016111661A1
Application number: PCT/TR2016/000003
Authority: WO
Inventors: Yildiztekin TUNCAY
Original assignee: Entovest İlaç Κi̇μυα Ve Teknoloji̇ Araştirma Merkezi Sanayi̇ Ti̇caret Li̇mi̇ted Şi̇rketi̇
Priority date: 2015-01-09
Filing date: 2016-01-11
Publication date: 2016-07-14

Abstract

The invention relates to the action that lasts at least 2-3 times longer than the other previous formulations (EW, EC) owing to the novel capsulation formulation of pyriproxyfen, which is used against the agricultural pests. The invention also relates to the use of the CS type in the control of the larvae and nymphs of mosquito- housefly-cockroach within the context of public health. The capsulation manufacturing technique and the superior efficacy obtained are within the scope of the invention.

Description

CAPSULE FORMULATION TECHNIQUE FOR INSECT GROWTH REGULATOR PYRIPROXYFEN, A JUVENILE HORMONE ANALOG Technical Field

The invention relates to the manufacture of the capsule formulation of pyriproxyfen molecule for use in the plant protection, the control of mosquito/housefly larvae and the control of insect pests in the veterinary hygiene and to the use thereof for the mentioned purpose. By means of the invention, prolonged action is obtained and the three (3) generations of the insect pests are taken under control with a single application.

The invention relates to the action that lasts at least 2-3 times longer than the other previous formulations (EW, EC, WDG, G) owing to the novel capsulation formulation of pyriproxyfen, which is used against the agricultural pests (larvae and nymphs) and the larvae of mosquito and housefly. Unlike the prior art, the capsules of pyriproxyfen according to the invention have been observed to be effective also on the insect pest eggs, in addition to the larvae and nymphs. The invention also relates to the use of the CS type in the control of the nymphs of flea and cockroach within the context of public health. The capsulation manufacturing technique and the superior efficacy obtained with this formula are also within the scope of the invention.

Prior Art

Currently, the conventional formulations used in the control of the pests and insects are classified into two groups, namely the liquid and solid formulations. The liquid formulations include Simple Solutions (Water Soluble Concentrates (SL), Solutions for Use in the Seed Dressing (LS), Liquid Formulations Dissolved in Oil (OL), Ultra Low Volume Liquids (UL), Dispersible Solutions (Emulsifiable Concentrates (EC), Dispersible Concentrates (DC), Emulsions (Emulsions (oil in water) (EW), Emulsions for Use in the Seed Dressing (ES), Micro-emulsions (ME), Suspensions (Aqueous Suspension Concentrates (SC), Suspension Concentrates Applied to Seeds (FS), Suspension Concentrates of Oil Origin (OD), Aqueous Suspo-emulsions (SE) and Dual Character Formulations. Solid formulations are classified as Directly Used Solid Formulations (Powder preparations (DP), Powders for Dry Application to the Seeds (DS), Granules (GR), Directly Used Tablets (DT), Solid Formulations used after Dispersion in Water (Wettable Powders (WP), Dispersible Powders for Use in the Seed Dressing (WS), Water Dispersible Granules (WG), Water Dispersible Tablets (WT), Emulsifiable Granules (EG), Emulsifiable Powders (EP), Solid Formulations used after Dissolution in Water (Water-Soluble Powders (SP), Water Soluble Powders for use in the Seed Dressing (WS), Water Soluble Granules (SG) and Water Soluble Tablets (ST)).

Also today, the pesticide manufacturers always search the ways for developing and formulating the pesticides in a way that is safer for the environment, humans and other non-targeted organisms, or they receive the support from the academic institutions in this regard. The increasing environmental consciousness and the research conducted about the harmful effects of the chemicals have accelerated these efforts even further. The harmful effects of the pesticides on the one hand and the health risks and economic losses caused by the insect pests on the other hand prompted the researches to seek a safer and more effective pesticide.

According to current practice, the emulsion concentrate (EC) and oil in water emulsion (EW) formulations of pyriproxyfen are used for the protection of plants. For the control of mosquito and housefly larvae, the formulation types of Emulsion Concentrate (EC), Suspension Concentrate (SC), Granule (Gr) and Water Dispersible Granule (WDG) are used. With the invention, it is aimed to develop the Capsule Suspension (CS, MC) formulation type of pyriproxyfen and to use the same in the control of the insect pests. SC, EC, WDG, Gr and EW formulation types lead to many undesirable results such as the irritation and the harmful effects of the auxiliary substances. Moreover, the fact that these formulation types do not provide the possibility of complete and continuous control of the insect pests due to their short duration of action urged the researchers and the specialists of the industry to seek new means of solutions. For this reason, many molecules other than pyriproxyfen are used by way of capsulation.

Further, the reduction of efficacy as a result of premature vaporization is another important problem with the formulations of the SC, EW, ME, SL, EC, WDG, OD and ODC type.

Until the present, pyriproxyfen has been used against the agricultural pests and other insect pests with the prior formulation types such as Emulsion Concentrate (EC), Oil in Water Formulation (Oil in Water Emulsion-EW), Granule (G) and Water Dispersible Granule (WG, WDG).

Some of these formulation types contain the auxiliary substances that are toxic to environment and non-targeted organisms. Moreover, efficacy of the prior formulations other than the Capsule Suspension (CS) allows the control of only one generation. Capsule suspension (CS) of pyriproxyfen is able to control 3-5 generations depending on the pest species.

The formulations used according to the state of the art for the purpose of plant protection and their ingredients are listed below:

I. Pyriproxyfen 10% EC

II. Pyriproxyfen 5% EC

III. Pyriproxyfen 5% WDG

IV. Pyriproxyfen 10% EW

The formulation types mentioned above provide control for a short time, and therefore they both necessitate too many applications in a season and lead to the result of the escape of the pests during the interim periods.

According to the state of the art, the invention no. US 20030181453 A1 entitled "Synergistic pesticide mixtures comprising pyriproxyfen and pyridaben, used for controlling insects, acarina or nematodes" relates to a pesticide composition comprising 4-phenoxyphenyl 2-(2-pyridyloxy)propyl ether and 2-tert-butyl-5-(4-tert- butylbenzylthio)-4-chloropyridazin-3(2H)-one as the active ingredients and to a method for controlling the pests by the use of 4-phenoxyphenyl 2-(2-pyridyloxy)propyl ether and 2-tert-butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin-3(2H)-one.

Further, the invention no. CN 101379982 B entitled "Insecticidal composition containing pyriproxyfen and avermectin" relates to a composition belonging to the technical field of pesticides and comprising pyriproxyfen and abamectin and synergy.

Further, the invention no. CN 103385251 A entitled "Insecticidal composition comprising pyriproxyfen" is an insecticidal composition comprising pyriproxyfen. Said invention provides synergic effect against various pests that damage the agricultural products. By means of the composition, the pesticide dose is reduced, the pesticide dose on the plants is reduced and the environmental pollution is reduced.

As result, the fact that the conventional formulation types of a molecule having effect on growth and development system during the egg, nymph and mature states of the pests does not allow the intended result and the need for novel formulation types providing longer duration of action have led to the development of the novel technique.

Object of the Invention

The object of the invention obtained based on the mentioned state of the art is to enable the formulation of pyriproxyfen molecule, which is used for the control of insect pests in the plant protection, public health (control of mosquito-housefly larvae) and the animal health, by means of the capsulation (CS, MC) technique being safer for the human and other non-targeted organisms, reducing/eliminating the problem of residue in the foods and the crops and providing prolonged action. Another object of the invention is to develop a novel formulation technique capable of controlling minimum 3 generations by means of a single application. This provides the possibility of both preventing the contamination of the environment and the products owing to the smaller amount of chemical used and of developing a control program with lower cost.

Another object of the invention is to achieve the control of the new resistant nymphs, which will hatch after the application of the pesticide, before they reach the mature state, owing to the insect growth regulator (IGR) active agents.

Another object of the invention is to prevent the labor losses by reducing the number of pesticide applications. Another object of the invention is to obtain a safer formulation with the water-based capsulation instead of the hazardous solvents and other auxiliary substances in the conventional formulations.

Another object of the invention is to provide a solution for the inability to achieve uninterrupted control between the generations, which is a problem of the prior art. Owing to the long term control provided by the capsulation technique, the uninterrupted control of the insect pests becomes possible.

In these studies;

1) The duration of action is prolonged as compared to the prior art, thereby reducing the number of applications during a season.

2) By means of the invention, the adverse effects seen in EC and EW formulations, such as irritation, etc. are eliminated.

3) Long duration of action as well as the possibility to achieve control with 2-fold lower dose explains that the invention has economic value.

4) Active agent is protected from the sun rays by the polymer shell.

In order to achieve the aforesaid objects, the pesticide composition is developed, which is described below with all the details and alternative embodiments. This composition is used for the control of pests in many fields, notably the agricultural pests. In order to provide the aforesaid advantages, the invention provides a capsule formulation of pyriproxyfen molecule for use in the control of insect pests in the plant protection, public health and animal health, comprising pyriproxyfen, emulsifier mixture, solvent, antimicrobial preservative agent, anti-foam agent, anti-freeze agent, reactant 1 , reactant 2, reactant 3, thickener and vehicle, wherein said formulation is safer for the human and other non-targeted organisms, reduces/eliminates the problem of residue in the foods and the crops and provides prolonged action.

The invention also provides a capsulation (CS, MC) method for said formulation comprising the process steps of mixing pyriproxyfen, solvent and capsule reactant 1 to prepare an emulsifiable pyriproxyfen solution, adding emulsifier mixture, antifreeze agent, antimicrobial preservative agent and anti-foam agent into the water to prepare the water phase of the emulsion, emulsifying the prepared pyriproxyfen solution in the water phase with the aid of a high-speed mixer, slowly adding the other reactants, i.e. reactant 2 and reactant 3, into the emulsion formed, resting the mixture in order to terminate the initiated polymerization reaction and then adjusting the viscosity with the aid of the thickener.

Tables;

Table.1. Agricultural Pests,

Table 2. General and preferred ratios of the ingredients constituting the invention Table 3. Test results about the efficacy

Detailed Description of the Invention The invention relates to the use of pyriproxyfen with the capsule suspension (CS) formulation type for the control of the pests in the plant protection (pests mentioned in the following table) and the public health (control of the mosquito and housefly larvae).

The technique for manufacturing the pesticide composition according to the invention is similar to the capsulation technique applications for the other pesticide molecules. The primary feature is the ability to obtain more effective result in the pest control, owing to the capsulation of the pyriproxyfen molecule. In the prior art, the capsulation form of pyriproxyfen was never tried in the plant protection, public health and animal health. Table.1. Agricultural Pests:

While the invention encompasses the encapsulation of the active agent pyriproxyfen via all the known methods, the following ratios and ingredients describe the preferred method of interfacial polymerization technique.

The following table provides the general and preferred weight ratios of the ingredients constituting the invention.

Table 2. General and preferred ratios of the ingredients constituting the invention

The manufacturing technique for the formulation with given contents by percentage comprises the following process steps:

— Mixing pyriproxyfen, solvent and capsule reactant 1 to prepare an emulsifiable pyriproxyfen solution

— Adding emulsifier mixture, anti-freeze agent, antimicrobial preservative agent and anti-foam agent into the water to prepare the water phase of the emulsion — Emulsifying the prepared pyriproxyfen solution in the water phase with the aid of a high-speed mixer

— Slowly adding the other reactants, i.e. reactant 2 and reactant 3, into the emulsion formed

— Resting the mixture in order to terminate the initiated polymerization reaction and then adjusting the viscosity with the aid of the thickener.

The emulsifier mixture mentioned in the table may be a combination of more than one emulsifier or may comprise a single emulsifier. These emulsifiers may belong to ionic, anionic and nonionic group or may be a combination of these groups. The emulsifiers able to be used in the product include amine ethoxylates, EO/PO block polymers, ether sulfates, saturated alcohol alkoxylates, saturated alcohol ethoxylates, sorbitan ester ethoxylates, tributylphenol ethoxylates, phosphate esters, tristryl phenol ethoxylates, sulfonation products, polycondensation products, nonyl phenol ethoxylates, alkyl benzene sulfonates, castor oil ethoxylates, EO/PO alkoxylation products, saturated alcohol ethoxylates, olein sulfonates and sulfosuccinate groups, which may be used alone or in combinations according to different proportions. In the formulation, a 1/1 mixture of tristryl phenol ethoxylate and nonyl phenol ethoxylate groups is preferably used. The solvent mentioned in the table is the liquid medium, in which the normally solid active agent pyriproxyfen is dissolved. Since the invention is realized with the interfacial polymerization technique, it may be formulated using only the water- insoluble solvents. In this regard, the hydrocarbons such as xylene, benzene, toluene, cyclohexane, solvesso 100, solvesso 150, solvesso 200 and exxsol series as well as the vegetable oils obtained from oily seeds, their ethyl and methyl esters and the terpenes of vegetable origin are encompassed by the invention. Instead of only one solvent, a combination of more than one solvent may also be used. In the formulation, the xylene solvent is preferably used. The anti-freeze agent mentioned in the table comprises the glycol derivatives that prevent the freezing at low temperatures as a known practice in the water-based pesticide formulations. These additives are ethylene glycol, monopropylene glycol, dipropylene glycol, diethylene glycol and glycerin. In the formulation, monopropylene glycol is preferably used.

The reactant 1 mentioned in the table refers to the organic compounds that contain isocyanate functional group. The function of the reactant 1 in the formulation is to polymerize on the emulsion droplets-water interface and form a polyurea capsule wall with the aid of catalyst solution following the formation of emulsion by way of addition thereof into the prepared pyriproxyfen oil phase. These compounds may be methyl isocyanate, methylene diphenyl diisocyanate (MDI), hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), naphthalene diisocyanate (NDI), methylene bicyclohexyl isocyanate (HMDI) or isophorone diisocyanate (IPDI).

Reactant 2 and reactant 3 mentioned in the table are amines that form a polyurea capsule shell by undergoing polymerization reaction with the reactant 1 , i.e. the isocyanate group. A premix of reactant 2 and reactant 3 is formed in water to prepare the catalyst solution. The prepared catalyst solution is slowly added on the pyriproxyfen oil phase emulsified in water, thereby initiating the reaction for the formation of the polyurea capsule shell. Amines used in the synthesis of the polyurea capsule shell may belong to the primary, secondary or tertiary amine groups. Said amines include ethylamine, ethylene diamine, diethylene triamine, triethylene tetraamine, dimethylamine, trimethylamine, diethylamine, diisopropylamine, dimethylaminopropylamine and triisopropylamine.

The thickener mentioned in the table refers to the additives able to be used for adjusting the viscosity of the formulation after the polymerization reaction terminates. These include xanthan gum, guar gum, gum arabic, carboxymethyl cellulose, methyl cellulose, hydroxypropyl cellulose. In the formulation, xanthan gum is preferably used.

The vehicle mentioned in the table is water and the anti-foam agent and the antimicrobial preservative agent are the products frequently used in the pesticide formulations. A silicone-based anti-foam agent is preferably used in the formulation.

Table 3. Test results about the efficacy

prior art (Dose: 50

ml/100 L water)

Insect control 85 98 84 94 composition

according to the

invention (Dose:

25 ml/100 L water)

Claims

1. The invention is a formulation of pyriproxyfen molecule for use in the control of insect pests in the plant protection, public health and animal health, which is safer for the human and other non-targeted organisms, reduces/eliminates the problem of residue in the foods and the crops and provides prolonged action, characterized in that it comprises pyriproxyfen, emulsifier mixture, solvent, antimicrobial preservative agent, anti-foam agent, anti-freeze agent, reactant 1 , reactant 2, reactant 3, thickener and vehicle.

2. A formulation according to Claim 1 characterized in that said emulsifiers may belong to ionic, anionic and nonionic group or may be a combination of these groups.

3. A formulation according to Claim 1 or 2 characterized in that said emulsifiers are selected individually or in combination from the group consisting of amine ethoxylates, EO/PO block polymers, ether sulfates, saturated alcohol alkoxylates, saturated alcohol ethoxylates, sorbitan ester ethoxylates, tributylphenol ethoxylates, phosphate esters, tristryl phenol ethoxylates, sulfonation products, polycondensation products, nonyl phenol ethoxylates, alkyl benzene sulfonates, castor oil ethoxylates, EO/PO alkoxylation products, saturated alcohol ethoxylates, olein sulfonates and sulfosuccinate groups.

4. A formulation according to Claim 1 or 3 characterized in that said emulsifiers may be used alone or in combinations according to different proportions.

5. A formulation according to Claim 1 characterized in that a 1/1 mixture of tristryl phenol ethoxylate and nonyl phenol ethoxylate groups is used.

6. A formulation according to Claim 1 characterized in that said solvent is the liquid medium, in which the normally solid active agent pyriproxyfen is dissolved.

7. A formulation according to Claim 1 or 6 characterized in that one or more said solvent is selected from the group consisting of hydrocarbons such as xylene, benzene, toluene, cyclohexane, solvesso 100, solvesso 150, solvesso 200 and exxsol series as well as the vegetable oils obtained from oily seeds, their ethyl and methyl esters and the terpenes of vegetable origin.

8. A formulation according to Claim 1 , 6 or 7 characterized in that said solvent is xylene.

9. A formulation according to Claim 1 characterized in that said anti-freeze agent comprises the glycol derivative that prevents the freezing at low temperatures in the water-based pesticide formulations.

10. An anti-freeze agent according to Claim 9 characterized in that it is ethylene glycol, monopropylene glycol, dipropylene glycol, diethylene glycol and glycerin.

11. An anti-freeze agent according to Claim 10 characterized in that it is monopropylene glycol.

12. A formulation according to Claim 1 characterized in that said reactant 1 refers to the organic compounds that contain isocyanate functional group.

13. A formulation according to Claim 1 or 12 characterized in that said reactant 1 is methyl isocyanate, methylene diphenyl diisocyanate (MDI), hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), naphthalene diisocyanate (NDI), methylene bicyclohexyl isocyanate (HMDI) or isophorone diisocyanate (IPDI).

14. A formulation according to Claim 1 characterized in that said reactant 2 and reactant 3 are amines that form a polyurea capsule shell by undergoing polymerization reaction with the reactant 1 , i.e. the isocyanate group.

15. A formulation according to Claim 1 or 12 characterized in that said reactant 2 and reactant 3, which are the amines used in the synthesis of the polyurea capsule shell, may belong to the primary, secondary or tertiary amine groups.

16. A formulation according to Claim 15 characterized in that the amines are selected from the group consisting of ethylamine, ethylene diamine, diethylene triamine, triethylene tetraamine, dimethylamine, trimethylamine, diethylamine, diisopropylamine, dimethylaminopropylamine and triisopropylamine.

17. A formulation according to Claim 1 characterized in that the thickener is selected from the group consisting of xanthan gum, guar gum, gum arabic, carboxymethyl cellulose, methyl cellulose, hydroxypropyl cellulose.

18. A formulation according to Claim 17 characterized in that said thickener is xanthan gum.

19. A formulation according to Claim 1 characterized in that said vehicle is water.

20. A formulation according to Claim 19 characterized in that said vehicle is silicone-based anti-foam agent.

21. A formulation according to Claim 1 characterized in that it comprises 0,001 - 85% by weight pyriproxyfen.

22. A formulation according to Claim 21 characterized in that it comprises 20% by weight pyriproxyfen.

23. A formulation according to Claim 1 , 2, 3 or 4 characterized in that it comprises 0,001-25% by weight emulsifier mixture.

24. A formulation according to Claim 23 characterized in that it comprises 6% by weight emulsifier mixture.

25. A formulation according to Claim 1 , 6, 7 or 8 characterized in that it comprises 5-50% by weight solvent.

26. A formulation according to Claim 25 characterized in that it comprises 22% by weight solvent.

27. A formulation according to Claim 1 characterized in that it comprises 0,01-59% by weight antimicrobial preservative agent.

28. A formulation according to Claim 27 characterized in that it comprises 0,03% by weight antimicrobial preservative agent.

29. A formulation according to Claim 1 characterized in that it comprises 0,01-60% by weight anti-foam agent.

30. A formulation according to Claim 1 characterized in that it comprises 1 % by weight anti-foam agent.

31. A formulation according to Claim 1 , 9, 10 or 11 characterized in that it comprises 0,1-60% by weight anti-freeze agent.

32. A formulation according to Claim 31 characterized in that it comprises 4% by weight anti-freeze agent.

33. A formulation according to Claim 1 , 12 or 13 characterized in that it comprises 0,01-70% by weight reactant 1.

34. A formulation according to Claim 33 characterized in that it comprises 5% by weight reactant 1.

35. A formulation according to Claim 1 , 14, 15 or 16 characterized in that it comprises 0,01-60% by weight reactant 2.

36. A formulation according to Claim 1 characterized in that it comprises 2% by weight reactant 2.

37. A formulation according to Claim 1 , 14, 15 or 16 characterized in that it comprises 0,01-70% by weight reactant 3.

38. A formulation according to Claim 37 characterized in that it comprises 1% by weight reactant 3.

39. A formulation according to Claim 1 , 17 or 18 characterized in that it comprises 0,001-30% by weight thickener.

40. A formulation according to Claim 39 characterized in that it comprises 0,08% by weight thickener.

41. A vehicle according to Claim 1 or 19 characterized in that it is used at a ratio to add up to 100% in the formulation.

42. The invention is a capsulation (CS, MC) method for the formulation of pyriproxyfen molecule according to any one of Claims 1 to 41 for use in the control of insect pests in the plant protection, public health and animal health, which is safer for the human and other non-targeted organisms, reduces/eliminates the problem of residue in the foods and the crops and provides prolonged action, characterized in that said method comprises the process steps of

mixing pyriproxyfen, solvent and capsule reactant 1 to prepare an emulsifiable pyriproxyfen solution,

adding emulsifier mixture, anti-freeze agent, antimicrobial preservative agent and anti-foam agent into the water to prepare the water phase of the emulsion, emulsifying the prepared pyriproxyfen solution in the water phase with the aid of a high-speed mixer,

slowly adding the other reactants, i.e. reactant 2 and reactant 3, into the emulsion formed,

resting the mixture in order to terminate the initiated polymerization reaction and then adjusting the viscosity with the aid of the thickener.

43. A method according to Claim 42 characterized in that said reactant 1 polymerizes on the emulsion droplets-water interface and forms a polyurea capsule wall with the aid of catalyst solution following the formation of emulsion by way of addition thereof into the prepared pyriproxyfen oil phase.

44. A method according to Claim 42 characterized in that said reactant 2 and reactant 3 form a polyurea capsule shell by undergoing polymerization reaction with the reactant 1 , i.e. the isocyanate group.

45. A method according to Claim 42 or 44 characterized in that a premix of reactant 2 and reactant 3 is formed in water to prepare the catalyst solution, the prepared catalyst solution is slowly added on the pyriproxyfen oil phase emulsified in water, thereby initiating the reaction for the formation of the polyurea capsule shell.