DESC:FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003

COMPLETE SPECIFICATION
(See section 10 and rule 13)

A SYNERGISTIC COMBINATION OF NEONICOTINOID AND INSECT GROWTH REGULATOR FOR COMBATING INSECT MENACE IN AGRICULTURE

Sumitomo Chemical India Ltd.,
a company incorporated in India, having address at
Building No. 1, Ground Floor, Shant Manor Co-op Housing Society Limited, Chakravarti Ashok ‘X’ Road, Kandivli (East), Mumbai, Maharashtra, India, 400101

The following specification particularly describes the invention and the manner in which it is to be performed.
FIELD OF THE INVENTION
The present invention relates to a synergistic combination of neonicotinoid and insect growth regulator for combating insect menace in agriculture.

BACKGROUND OF THE INVENTION
This invention pertains to novel synergistic combination of neonicotinoid and insect growth regulator, used as insecticides for protecting agricultural crops from infestation of insect pests. Neonicotinoids are a class of neuro-active insecticides having mode of action similar to the natural insecticide nicotine. They selectively bind and interact with the insect nicotinic acetylcholine receptor site (nAChRs) exhibiting high selective toxicity to insects over vertebrates and good systemic activity in crops. From Neonicotinoid class of chemicals, Clothianidin was selected as a mixture partner to combine with other different chemical class i.e. Insect Growth Regulators (IGR). Pyriproxyfen, a juvenile hormone analog and an insect growth regulator was taken as another active ingredient for the said combination. It prevents larvae from developing into adulthood and thus rendering them unable to reproduce. Pyriproxyfen mimics a natural hormone in insects and disrupts their growth. It is effective against a variety of insects.
The two insecticides are combined in a particular ratio to show greater insecticidal activity / better bioefficacy than that of the individual insecticides. Each of the two components of the novel synergistic compositions of this invention belong to the applicant. For instance, Clothianidin 50% WDG, Clothianidin 0.5 GR, Pyriproxyfen 10% EC, Pyriproxyfen 10% EW have been invented and developed by Sumitomo Chemical India Limited (hereinafter named as SCIL). These are registered for use as single active ingredient (formulation having only one insecticide) providing control of only a few insect pests as every molecule has its capacity to show its efficacy. At times, this becomes a limitation of formulations based on single insecticide and farmers need to use multiple products for controlling different insect pests, which might lead to deploying labors each time for performing spray application of single insecticide-based products. This becomes a cumbersome and cost-intensive affair. Mixture products of Pyriproxyfen in combination with other active ingredients are available. Similarly, a mixture product of Clothianidin is also available. Development of Combination products has been in existence for long. However, choosing two active ingredients at the optimum strengths delivering better results than its individual components require a lot of precision, analytical ability and dedicated research & development efforts. Developing a mixture product based on neonicotinoid and insect growth regulator classes of chemicals was the challenging task and keeping that in view, SCIL invented a unique formulation of two insecticides i.e. Clothianidin and Pyriproxyfen. A distinctive strength of these two insecticides was devised by SCIL in order to get better performance than its individual components. After many years of research, the mixture formulation proved to be novel in many aspects: a) This combination product was effective against variety of insect pests and the same spectrum of efficacy was not achieved against all such pests together by its individual components. b) The mixture product was found stable for two years. c) Both the individual molecules i.e. Clothianidin and Pyriproxyfen belong to different chemical groups and have different mode of actions, which make them ideal mixture partners for using in Integrated Pest Management practices as well as resistance management strategies. d) There has not been any mixture commercialized in India based on Clothianidin and Pyriproxyfen. e) This mixture product has exhibited its bioefficacy on two different types of crops i.e. cotton, a fibre crop and brinjal, a vegetable crop. Both the crops harbor variety of insect pests and due to this, farmers come across with a lot of economic losses. In view of above, the said mixture product can be considered as novel and a boon to Indian Farmers.

DESCRIPTION OF THE INVENTION
Insecticides are those substance(s) or a combination of substances whose primary function when applied to plants, seeds or rhizosphere is to control various types of insect pests, which are either directly harmful to crops or indirectly interrupt crop growth. Such impact on crops deprive them from nutrient uptake, growth, yield, nutrition efficiency, crop quality, etc. Such insecticide mixture could be used / applied on agricultural crops as a part of Integrated Pest Management practices to protect them from insect pests and thereby enhancing yields.
Synergism is the cooperative action encountered in combinations of two insecticides in which the combined activity of two compounds exceeds the sum of the activities of the compounds when used alone. Keeping this in view, the preferred formulation of the present invention was kept suspoemulsion denoted as SE. Suspoemulsion (SE) formulation was used to combine two active ingredients with different properties into one formulation. They are a combination of two technologies - suspension concentrate (SC) and concentrated aqueous emulsion (EW). The advantages of this particular type of formulation is that it is possible to formulate more than one active ingredient together, broadening the spectrum of activity.
This invention relates to a combination of Clothianidin and Pyriproxyfen developed with other ingredients e.g. adjuvants, inerts, etc and a SE type formulation was prepared by SCIL for protecting crops from insect pests, increasing yields of crops, economically important crops or any other agriculturally important crops. The present invention relates to mixtures having synergistically enhanced action and to a method of improving the health of plants by applying said mixtures to the plants or the locus thereof. An important aspect of this invention is to primarily aim to protect crop from insect pests.
The results show the marked synergistic interaction of the compositions of the invention. A wide range of ratios of individual components were evaluated and it was found that the mortality of insect pests occurred due to synergistic effect of this combination is unexpectedly greater than that to be expected from the added effects of the individual components. This result is particularly striking in view of the fact that the said mixture product proved to be safer to various crops including cotton and brinjal crops as the results reveal that there was no phytotoxicity reported even at double the optimum dose of this mixture. The synergistic compositions of this invention may be employed to control a variety of crop pests particularly in cotton and brinjal, however, experimental trials on various other aspects are still in progress. The mixture formulation is prepared by inincorporating the suitable adjuvants, carriers and other ingredients in order to provide stability to the formulation for at least up to two years without impacting its bioefficacy parameters.
1. Detailed Description of the Invention
The present invention provides synergistic composition comprising:
Component Qty. (% w/w)
Clothianidin a.i 3.50%
Pyriproxyfen a.i 8.00%
Naphtha (Petroleum) heavy aromatic solvent 15.53%
Polyethylene –polypropylene glycol 0.97%
Lignin sulfomethylated 2.52%
Siloxanes 0.19%
1,2-Benzisothiazole-3(2H)-one 0.19%
MgAl silicates / Bentonite 0.43%
Xanthan Gum 0.21%
Propylene Glycol 4.37%
Deionized water QS to make 100%
Total 100.00%

The said synergistic combination of insecticides can be used to increase overall health of crops / plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops or useful plants, while at the same time those parts of plants which grow later are also affected positively.
The ratio of Clothianidin and Pyriproxyfen and the amount of other ingredients in the mixture formulation are devised in a way so that it gives optimum efficacy against insect pests when used in agricultural fields on crops. Yield increase in crops can also be obtained by use of this mixture.
The optimum ratios and total amounts to be employed can in each case be determined by routine experimentation.

Manufacturing Process of Clothianidin 3.5% + Pyriproxyfen 8% SE
Stepwise Details:
Phase – A:
Oil phase: Charging & Mixing: As per recipe, charge the Solvent, Start stirrer. Then charge Pyriproxyfen technical material into a mixing vessel at ambient temperature, mix well till the material get homogeneous liquid.
Phase – B:
Charging & Mixing: As per recipe, charge the soft water, Start stirrer. Then add raw materials Clothianidin technical, adjuvants & emulsifier as per charging sequence into a mixing vessel at ambient temperature, mix well until the material get homogeneous liquid. Add phase A and mix well.
Phase – C:
Gum dispersion: Charging & Mixing: As per recipe, charge the anti-freezing agent into small vessel, Start stirrer. Then add thickener powder, mix it till the material is homogenize.
Thickener solution: Charge required quantity of water as per recipe into a stirrer, start stirrer and add anti-fungal agent then add Gum dispersion and mix it till the material is homogenize.
Process:
Mill phase B into bead mill. Check particle size. If desired particle size achieved, transfer the milled material into a post mixer then add phase C Thickener solution. Mix it till the thickener solution completely disperse. Draw the sample and analyse. If material meet the specification, pack it as per production plan.

Analytical Test Report:
The Analytical Test Report of Clothianidin 3.5%w/w + Pyriproxyfen 8.0%w/w SE is as below:
PARAMETERS OBSERVATIONS*
Sample -1 Sample -2
Appearance The material is in the form of brown coloured liquid free from extraneous matter
pH of 1% aq. solution (25± 1°C) 8.02 8.04
Persistent foam (mL) 2.5 2.5
Wet sieve test
(% material passed through 75 µm) 99.89 99.86
Density (g/mL) 1.035 1.031
Pourability (%)
Residue 0.030 0.029
Rinsed residue 0.007 0.008
Dispersion stability Initial dispersion
0 Hour No sediment and no top cream or oil
0.5 Hour No sediment and no top cream or oil
Re-dispersion 24 hour 2.0 mL of top cream formed
24.5 Hour No sediment and no top cream or oil
Suspensibility
(% w/w) Clothianidin 98.90 98.86
Pyriproxyfen 99.93 99.87
Clothianidin content (% w/w) 3.53 3.51
Pyriproxyfen content (% w/w) 8.06 8.06
*- Average of two replications
Shelf Life
A 30 month storage stability/ shelf-life study was conducted on Clothianidin 3.5%w/w + Pyriproxyfen 8.0%w/w SE. The samples are stored at three different agroclimatic locations viz., Coimbatore (Location 1), Mumbai (Location 2) and Delhi (Location 3). The study time-points of analysis are 0, 6, 12, 18, 24 and 30 months after storage. The study was initiated during January 2015 and the active ingredient content of Clothianidin and Pyriproxyfen with physic-chemical properties such as pH, Persistent foam, Wet sieve, Density, Pourability, Dispersion stability and Suspensibility were studied. The content of Clothianidin and Pyriproxyfen was analysed by HPLC-DAD method.
Analysis of samples collected from three different locations during the 30 months storage (July 2017), showed no significant change in the physico-chemical properties as well as the active ingredient content of Clothianidin and Pyriproxyfen. During the above storage period, the representative packaging material was observed for their specifications, container conditions, as well as performance parameters recommended by CIB & RC. Results showed no significant changes with respect to the above parameters.
Conclusion
Based on the stability analysis, it can be concluded that the shelf life of the Clothianidin 3.5% + Pyriproxyfen 8% SE is 2 years.

BIO-EFFICACY OF CLOTHIANIDIN 3.5% + PYRIPROXYFEN 8% SE (SCPC 835 SE)
COTTON
The bio-efficacy of the mixture product was evaluated for controlling insect Pests of cotton crop at MPUAT, Udaipur (Banswara), Rajasthan; RVSKVV Gwalior (R.A.R. Station- Khandwa) and Viswa-Bharati University, Sriniketan, Birbhum, West Bengal

MPUAT, Udaipur (Banswara)
Based on two years field experiments which were conducted during kharif-2016 and kharif=2017, the below mentioned findings can be concluded:
1. Among the doses of test chemical i.e. SCPC-835 SE @ 1500 and 1250 ml ha-1 were found very effective in controlling the population of whiteflies, jassids, thrips and aphids and are statistically at par.
2. SCPC-835 SE was found safe on crop as it did not cause phytotoxicity in any form (leaf injury, wilting, stunting, vein clearing, necrosis, chlorosis, epinasty and hyponasty) even spray up to 2500 ml ha-1.
3. SCPC-835 SE applied as foliar spray was safer to natural enemies in the cotton ecosystem under field conditions.

RVSKVV Gwalior (R.A.R. Station- Khandwa)
Based on two years field experiments which were conducted during kharif-2016 and kharif-2017, the findings can be concluded as below -
1. Both the doses of test chemical i.e. SCPC-835 SE @ 1500 and 1250 ml/ ha were found very effective in controlling the population of whiteflies, jassids, thrips and aphids and are statistically at par.
2. SCPC-835 SE was found safe on crop as it did not cause phytotoxicity in any form (leaf injury, wilting, stunting, vein clearing, necrosis, chlorosis, epinasty and hyponasty) even spray up to 2500 ml/ ha.
3. SCPC-835 SE applied as foliar spray was found safer to natural enemies in the cotton ecosystem.
Viswa-Bharati University, Sriniketan, Birbhum, West Bengal
It was observed during the course of two season studies with SCPC 835 SE against whitefly, that SCPC 835 SE @1250 ml/ha (44+100 g a.i. /ha) and 1500 (52.5+120) provided good control of Cotton Whitefly and other sucking pests i.e. Jassids, Aphids and Thrips along with significant yield increase. No phytotoxic symptoms on Cotton plant were observed in any of the treated plots with SCPC 835 SE even its double dose. The chemical was safer to two important natural enemies.
BRINJAL
The bio-efficacy of the mixture product was evaluated for controlling insect Pests of brinjal crop at MPUAT, Udaipur (Banswara), Rajasthan; GBPUAT Pantnagar (Uttarakhand) and Viswa-Bharati University, Sriniketan, Birbhum, West Bengal
MPUAT Rajasthan
Field experiments on the bio-efficacy of SCPC- 835 SE at 35+80 g a.i. /ha, 44+100 g a.i. /ha and 52.5+120 g a.i./ha along with alone reference checks viz. Clothianidin 50% WDG 25, Pyriproxyfen 10% EC 100 g a.i./ha against whitefly and other sap sucking insect pests of brinjal and experiment was conducted at Horticulture Farm, Rajasthan College of Agriculture, Udaipur during Kharif, 2016 and Rabi, 2017. The data revealed that three sprays of SCPC- 835 SE @ 52.5+120 g a.i. /ha at 15 days interval caused highest reduction in the population of whitefly and other sap sucking insect pests of brinjal and recorded the highest marketable fruit yield of brinjal which is at par with three sprays of SCPC- 835 SE at the doses of 44+100 g a.i. /ha and found significantly superior over alone reference checks viz. Pyriproxyfen 10% EC at 100 g a.i. /ha and Clothianidin 50% WDG at 25 g a.i. /ha for the control whitefly and other sap sucking insect pests of brinjal. Spray of SCPC- 835 SE at the different doses did not cause adverse effect on common natural enemies present in brinjal ecosystem and even at its double dose of 88+200 g a.i. /ha did not produce any visible phytotoxicity symptoms in brinjal crop. Hence, two season / years study revealed that the SCPC 835 SE @ 44 + 100 g a.i/ha (1250 ml/ha) can be recommended to control whitefly and other sap sucking pests viz. Aphid, Jassids and Thrips of Brinjal crop.
GBPUAT Pantnagar (Uttarakhand)
SCPC-835 SE @1500 ml/ha and SCPC-835 SE @1250 ml/ha was found to be highly effective for management of whitefly, aphid, thrips and jassids in brinjal crop. Brinjal whitefly and other sucking pests multiply faster with higher fecundity thus this application of SCPC-835 SE formulation @1500 and SCPC-835 SE @1250 ml/ha at the interval of 15 days is suitable for managing whitefly aphid, thrips and jassids in brinjal crop. There were no adverse effects of SCPC-835 SE formulation on natural enemies at doses applied. The SCPC-835 SE formulation @1500 ml/ha and @1250 ml/ha were found to be safe to natural enemies. There was no phytotoxicity effect of SCPC-835 SE formulation even at the dose of @2500 ml/ha on brinjal.

Sriniketan, Birbhum (West Bengal)
It is evident from the study conducted during 2016 and 2017 that SCPC 835 SE @ 1250 ml/ha gave excellent control of whitefly and other sucking pest viz Aphid, Thrips & Jassids of Brinjal crop along with significant yield increase. The test chemical has significant better efficacy over its alone components viz. Pyriproxyfen 10% EC & Clothianidin 50% WDG and was safer to two important natural enemies. The product did not show any phytotoxicity symptoms on brinjal crop.
Clothianidin 3.5% + Pyriproxyfen 8% SE
Toxicity studies
1. Acute Oral toxicity in Rat: LD50: 5000 mg/kg
2. Acute Dermal toxicity in Rat: LD50: >5000 mg/kg b.wt.
3. Acute Inhalation toxicity to Rat: LC50: >4.27 mg/L
4. Acute Dermal Irritation to Rabbit: Mild-Irritant
5. Irritation to mucous membrane: Non -Irritant
6. Skin senitization-Guinea Pig: Non -sensitizer.
7. Acute oral toxicity in Chicken: LD 50 >2000 mg/kg b.wt
8. Acute oral toxicity in Pigeon:LD 50 >2000 mg/kg b.wt
9. Toxicity to fish: LC 50 (96h) - 3.39 mg/L
10. Toxicity to Honeybee – Apis mellifera (oral): LD 50 ( 24 h and 48h) oral - 0.07 ug a.i/bee
11. Toxicity to Honeybee – Apis mellifera (contact): LD 50 ( 48h) contact- 0.24 ug a.i/bee
12. Toxicty to Earthworm (Eiesnia foetida): LC50 – 291.7 mg/kg of artificial soil

INDUSTRIAL APPLICABILITY AND ECONOMICAL SIGNIFICANCE
The synergistic insecticidal composition, wherein Clothianidin and Pyriproxyfen are mixed in a distinctive strength as Clothianidin 3.5% and Pyriproxyfen 8% in the formulated product, can be considered as a novel invention. This mixture product of two insecticides (in the distinctive strength as mentioned above) provides better performance (bioefficacy) than its individual components due to the following aspects: a) This combination product is effective against variety of insect pests and the same spectrum of efficacy is not achieved against all such pests together by its individual components. b) The mixture product is found stable for two years, which could be an advantage for its commercialization c) Both the individual molecules i.e. Clothianidin and Pyriproxyfen belong to different chemical groups and have different mode of actions, which make them ideal mixture partners for using in Integrated Pest Management practices as well as resistance management strategies. d) There has not been any mixture commercialized in India based on Clothianidin and Pyriproxyfen. e) This mixture product has exhibited its bioefficacy on two different types of crops i.e. cotton, a fibre crop and brinjal, a vegetable crop. Both the crops harbor a variety of insect pests and due to this, farmers come across with a lot of economic losses. Therefore, this mixture can be considered worthy to farmers earning better profits from their farm outputs.
The foregoing description of the invention has been set merely to illustrate the invention and is not intended to be limiting. Since modifications of the disclosed embodiments incorporating the substance of the invention may occur to persons skilled in the art, the invention should be construed to include everything within the scope of the disclosure.
,CLAIMS:We claim:
1. A synergistic insecticidal composition comprising:
a. Clothianidin in the range of 0.1% to 80% w/w;
b. Pyriproxyfen in the range of 0.1% to 80% w/w; and
c. at least one excipient in the range of 0.05% to 80% w/w.
2. The synergistic insecticidal composition as claimed in Claim 1, wherein Clothianidin is 3.50% w/w, and Pyriproxyfen is 8.0% w/w.
3. The synergistic insecticidal composition as claimed in Claim 1, wherein excipients are selected from the group consisting of wetting agent, thickner, sticking agent, anti-freezing agent, dispersant, anti-foam agent/defoamer, suspension aid, anti-microbial/anti-fungal/anti-bacterial agent, binders / stickers, buffering agent, and surfactant, etc.
4. The synergistic insecticidal composition as claimed in Claim 1, wherein the excipients comprise of:
a. Naphtha (petroleum) heavy aromatic solvent;
b. Polyethylene – polypropylene glycol;
c. Lignin sulfomethylated;
d. Siloxanes;
e. 1,2 – Benzisothiazole 3(2H)-one;
f. MgAl silicates / bentonite;
g. Xanthan gum;
h. Propylene glycol; and
i. Deionized water.
5. The synergistic insecticidal composition as claimed in Claim 4, wherein each excipient is in the range of 0.05 % to 80%
6. The synergistic insecticidal composition as claimed in Claim 4, wherein excipient comprises:
a. 15.53% w/w Naphtha (Petroleum) heavy aromatic solvent;
b. 0.97% w/w Polyethylene –polypropylene glycol;
c. 2.52% w/w Lignin sulfomethylated;
d. 0.19% w/w Siloxanes;
e. 0.19% w/w 1,2-Benzisothiazole-3(2H)-one;
f. 0.43% w/w MgAl silicates / Bentonite
g. 0.21% Xanthan Gum;
h. 4.37% Propylene Glycol; and
i. Q.S. to make 100% Deionized water.
7. The synergistic insecticidal composition as claimed in any of the preceding claims, wherein the said composition is used to control insect and/or pests in conventional, hybrid, and genetically modified varieties of crop and vegetable, including, brinjal (Solanum melongena), cabbage (Brassica oleracea var. capitata), cauliflower (Brassica oleracea var. botrytis), broccoli (Brassica oleracea var. italica), tomato (Solanum lycopersicum), potato (Solanum tuberosum), capsicum (Capsicum annuum), onion (Allium cepa), beetroot (Beta vulgaris subsp. vulgaris), carrot (Daucus carota), cucumber (Cucumis sativus), bitter gourd (Momordica charantia), bottle gourd (Lagenaria siceraria), snakegourd (Trichosanthes cucumerina), pumpkin (Cucurbita), pointed gourd (Trichosanthes dioica), okra (Abelmoschus esculentus), peas (Pisum sativum), spinach (Spinacia oleracea)]; cereals [wheat (Triticum spp), paddy (Oryza sativa), maize (Zea mays), barley (Hordeum vulgare), sorghum (Sorghum bicolor)]; oilseed crops [cotton (Gossypium spp), soybean (Glycine max), sunflower (Helianthus annuus), sesame (Sesamum indicum), rapeseed mustard (Brassica napus), peanut (Arachis hypogaea), coconut (Cocos nucifera)]; plantation crops [sugarcane (Saccharum officinarum), coffee (Coffea arabica), tea (Camellia sinensis)]; pulse crops [pigeon pea (Cajanus cajan), cowpea (Vigna unguiculata), black gram (Vigna mungo), green gram (Vigna radiata), bengal gram (Cicer arietinum), red kidney beans (Phaseolus vulgaris L.), black eyed peas (Vigna unguiculata), lentil (Lens culinaris), white peas (Lathyrus sativus), etc]; fruits [apple (Malus), grape (Vitis vinifera), mango (Mangifera indica), banana (Musa), plum (Prunus domestica), peach (Prunus persica), cherry (Prunus avium), lemon/orange/mandarin (Citrus spp), gooseberry (Ribes uva-crispa), strawberry (Fragaria spp), guava (Psidium guajava), litchi (Litchi chinensis), pineapple (Ananas comosus), sapota (Manilkara zapota)]; spices [cardamom (Elettaria cardamomum), black pepper (Piper nigrum), coriander (Coriandrum sativum), cumin (Cuminum cyminum), cloves (Syzygium aromaticum), turmeric (Curcuma longa), ginger (Zingiber officinale), cinnamon (Cinnamomum verum)].
8. The synergistic insecticidal composition as claimed in any of the preceding claims, wherein the said composition controls insects and/or pests from order including, Hemiptera [whiteflies (Bemisia tabaci; Bemisia spp.), aphids (Aphis gossypii; Aphis spp.), jassids/leafhoppers (Amrasca biguttula; Amrasca spp.) Thysanoptera [thrips (Thrips tabaci; Thrips spp)].
9. The synergistic composition as claimed in Claim 1 to 6, wherein the said synergistic composition can be formulated in different formulations, including, Suspoemulsion (SE), Suspension Concentrate (flowable concentrate) (SC), Capsule Suspension (CS), Dispersible Concentrate (DC), Oil Dispersion (OD), combination / mixture of SC and CS (ZC), a mixed formulation of CS and SE (ZE), a mixed formulation of CS and EW (ZW), Water Soluble Granules (SG), Water Dispersible Granules (WDG / WG), Water Soluble Bags, Wettable Powder (WP), or Soluble Powder (SP).