WO2022023366A1 - Insect control composition - Google Patents

Insect control composition Download PDF

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Publication number
WO2022023366A1
WO2022023366A1 PCT/EP2021/071049 EP2021071049W WO2022023366A1 WO 2022023366 A1 WO2022023366 A1 WO 2022023366A1 EP 2021071049 W EP2021071049 W EP 2021071049W WO 2022023366 A1 WO2022023366 A1 WO 2022023366A1
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WIPO (PCT)
Prior art keywords
insect control
limonene
control composition
composition according
geraniol
Prior art date
Application number
PCT/EP2021/071049
Other languages
French (fr)
Inventor
Avijit DAS
Prerna DHAWADE
Sumana DUTT CHOUDHURY
Mayank Kapoor
Anil Kumar MAKKAPATI
Bhagyasree MIRIYALA RAMESHBABU
Kunal Mukhopadhyay
Pranoti PATHAK
Sandeep Kumar SATHUA
Shanthakumar SHANMUGAM PERUMAL
Vimmy SUVARNA
Adeeti VERMA
Original Assignee
Reckitt & Colman (Overseas) Hygiene Home Limited
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Publication date
Application filed by Reckitt & Colman (Overseas) Hygiene Home Limited filed Critical Reckitt & Colman (Overseas) Hygiene Home Limited
Priority to AU2021318836A priority Critical patent/AU2021318836A1/en
Publication of WO2022023366A1 publication Critical patent/WO2022023366A1/en

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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08Oxygen or sulfur directly attached to an aromatic ring system
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/02Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
    • A01N25/04Dispersions, emulsions, suspoemulsions, suspension concentrates or gels
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/30Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests characterised by the surfactants
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N27/00Biocides, pest repellants or attractants, or plant growth regulators containing hydrocarbons
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/02Acyclic compounds
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/06Unsaturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N49/00Biocides, pest repellants or attractants, or plant growth regulators, containing compounds containing the group, wherein m+n>=1, both X together may also mean —Y— or a direct carbon-to-carbon bond, and the carbon atoms marked with an asterisk are not part of any ring system other than that which may be formed by the atoms X, the carbon atoms in square brackets being part of any acyclic or cyclic structure, or the group, wherein A means a carbon atom or Y, n>=0, and not more than one of these carbon atoms being a member of the same ring system, e.g. juvenile insect hormones or mimics thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/08Magnoliopsida [dicotyledons]
    • A01N65/22Lamiaceae or Labiatae [Mint family], e.g. thyme, rosemary, skullcap, selfheal, lavender, perilla, pennyroyal, peppermint or spearmint
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/08Magnoliopsida [dicotyledons]
    • A01N65/28Myrtaceae [Myrtle family], e.g. teatree or clove
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/08Magnoliopsida [dicotyledons]
    • A01N65/36Rutaceae [Rue family], e.g. lime, orange, lemon, corktree or pricklyash
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • A01N65/40Liliopsida [monocotyledons]
    • A01N65/44Poaceae or Gramineae [Grass family], e.g. bamboo, lemon grass or citronella grass
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01PBIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P17/00Pest repellants
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01PBIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00Arthropodicides
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present disclosure relates to an insect control composition.
  • the present disclosure relates to an insect control composition that has high activity against mosquito larvae and pupae, while being safe to use around children and household pets.
  • Insect borne diseases are a serious threat to public health.
  • Mosquitoes for instance, are the primary carrier for parasites that cause malaria and viruses that cause dengue fever, Chikungunya, Zika and yellow fever.
  • Several approaches have been developed for managing mosquito populations and mitigating the threat to health posed by mosquitoes. The most common approach is to use a chemical insecticide to kill mosquito larvae or pupae or to repel or kill adult mosquitoes.
  • chemical insecticides can be toxic to humans and other non-target organisms.
  • the widespread global use of chemical insecticides has resulted in mosquitoes developing resistance to many chemical insecticides. Similar issues have been reported in relation to other insect pests, such as cockroaches.
  • Natural products such as essential oils, have gained significant interest as potential vector control agents in view of their high target specificity and low toxicity towards humans and other non-target organisms. They are also friendlier to the environment than chemical insecticides and do not tend to accumulate along food chains.
  • Several essential oils have been investigated as potential insecticides. In one study, thyme oil, catnip oil, amyris oil, eucalyptus oil and cinnamon oil were tested against mosquito larvae and as repellents against adult mosquitoes (see Zhu et al., Journal of the American Mosquito Control Association, 2006, 22(3): 515-5220). In another study, the larvicidal and repellent potential of Mentha piperita essential oil was investigated (see Kumar et al., Asian Pacific Journal of Tropical biomedicine, 2011 , 1(2): 85-88).
  • Emulsified oil-in-water product forms are desirable for use in coolers, accumulated waters, overhead tanks and the like, as well as for use in sprays, and it is believed that such formulations could provide a potent mode for making insect repellents and killing products.
  • the present inventors have found that providing a physically stable formulation of certain essential oil components (that is, without phase separation) is extremely challenging.
  • the requirement for a surfactant can influence the interaction of the oils with the target organism. For instance, surfactants can change the wettability of mosquito larvae, affecting their ability to incorporate essential oils. Accordingly, even if an essential oil or a component thereof has known insecticidal activity, this does not necessarily mean that the insecticidal activity will be high once incorporated into a surfactant- containing oil-in-water dispersion.
  • an environmentally friendly insect control composition having high insecticidal activity, for instance against mosquito larvae and mosquito pupae.
  • the present invention provides an insect control composition
  • a continuous aqueous phase comprising a continuous aqueous phase, a discontinuous oil phase and a non-ionic surfactant, wherein the discontinuous oil phase comprises:
  • Basil oil geraniol, 1,8-cineole or a combination thereof, preferably basil oil.
  • the present inventors have found that this combination of essential oil components (thymol, limonene, and basil oil, geraniol and/or 1,8-cineole), in combination with a non-ionic surfactant, is particularly effective at killing mosquito larvae and pupae. It has also been found that it is possible to provide aqueous dispersions of these essential oil components exhibiting high physical stability.
  • the composition according to the invention comprises a continuous aqueous phase, a discontinuous oil phase and a non-ionic surfactant, wherein the discontinuous oil phase comprises: thymol, limonene; and basil oil.
  • the present inventors have inventors have found that the combination of thymol, limonene, and basil oil; in combination with a non-ionic surfactant, provides aqueous dispersions (i.e. , the composition is diluted in water), which exhibit high physical stability and are particularly effective at killing mosquito larvae and pupae after only 4 hours.
  • the present invention provides a bottle comprising an insect control composition as defined in relation to the first second aspect.
  • the present invention provides a method for killing or repelling insects comprising applying to the insects or to a target site of insect activity or infestation an insect control composition as defined in relation to the first aspect.
  • the present invention provides a use of an insect control composition as defined in relation to the first aspect for killing or repelling insects.
  • the present invention provides a method for manufacturing an insect control composition, the method comprising mixing thymol, limonene, and basil oil, geraniol, and/or 1 ,8-cineole, a non-ionic surfactant and water to form an insect control composition comprising a continuous aqueous phase, a discontinuous oil phase and the non ionic surfactant, wherein the discontinuous oil phase comprises the thyme oil, the limonene, and the basil oil, the geraniol, and/or the 1,8-cineole.
  • insect control composition it is meant a composition capable of killing or repelling insects, such as mosquitoes, cockroaches, houseflies, fruit flies, fleas, ticks weevils, ants, aphids, billbugs and moths.
  • insect control composition a composition capable of killing or repelling insects, such as mosquitoes, cockroaches, houseflies, fruit flies, fleas, ticks weevils, ants, aphids, billbugs and moths.
  • insect control composition when used as an insecticide, can be used in coolers, accumulated waters, or overhead tanks.
  • insect control composition when used as an insect repellent, the composition is preferably suitable for topical application. That is, the composition is preferably suitable for direct application to a part of the human or animal body. Preferably, the composition is suitable for direct application to the skin, for example the face, scalp, feet, limbs or trunk.
  • the insect control composition comprises a continuous aqueous phase and a discontinuous oil phase.
  • the composition comprises a dispersion of a discontinuous oil phase in a continuous aqueous phase.
  • the phases are physically distinct.
  • the continuous aqueous phase comprises water and, optionally, a polar water-miscible liquid such as those described herein.
  • the discontinuous oil phase is present in an amount of at least 5 wt% by weight of the composition, more preferably from 6 to 15 wt%, and most preferably from 8 to 12 wt%.
  • the discontinuous oil phase comprises thymol.
  • Thymol is also known as 2-isopropyl-5- methylphenol (IPMP). It is a monoterpenoid phenol derivative of cymene, found in thyme oil.
  • IPMP 2-isopropyl-5- methylphenol
  • the thymol used in the present invention is obtained from thyme oil (an essential oil), although it may alternatively be produced synthetically.
  • the thymol is present in an amount of from 1 to 5 wt% by weight of the composition, more preferably from 2 to 4 wt%.
  • the discontinuous oil phase further comprises limonene.
  • Limonene (1-methyl-4-(prop-1-en- 2-yl)cyclohex-1-ene) is a colourless liquid aliphatic hydrocarbon classified as a cyclic monoterpene, and is the major component in the oil of citrus fruit peels.
  • the limonene preferably is or comprises D-limonene.
  • the limonene used in the present invention is obtained from citrus fruit rind, for instance orange rind or lemon rind, although it may alternatively be produced synthetically.
  • the limonene is present in an amount of from 1 to 10 wt% by weight of the composition, more preferably from 2 to 8 wt%, and most preferably from 4 to 6 wt%.
  • the discontinuous oil phase further comprises basil oil, geraniol, and/or 1 ,8-cineol, preferably basil oil.
  • Basil oil is an essential oil obtained from the basil leaves and flowering tops ( Ocinum basilicum L or sweet basil). Its main constituent (at least 70%) is methyl cinnamate.
  • Geraniol ((2E)-3,7-Dimethyl-2,6-octadien-1-ol) is an alcohol monoterpenoid. It is the primary component of rose oil, palmarosa oil and citronella oil. Preferably, the geraniol, where used in the present invention, is obtained from rose oil, palmarosa oil or citronella oil, although it may alternatively be produced synthetically.
  • 1,8-cineole (1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octane, also known as eucalyptol) is a cyclic ether monoterpenoid and is the primary component of eucalyptus globulus oil.
  • the 1,8-cineole where used in the present invention, is obtained from eucalyptus globulus oil, although it may alternatively be produced synthetically.
  • the basil oil, the geraniol, the 1,8-cineole, or the combination thereof is present in an amount of from 0.3 to 5 wt.% by weight of the composition, more preferably from 0.5 to 5 wt.%, most preferably from 0.5 to 4 wt.%.
  • the composition comprises geraniol
  • the geraniol is preferably present in an amount of from 1 to 5 wt.%, more preferably from 2 to 4 wt.%.
  • the composition comprises 1,8-cineole
  • the 1 ,8-cineole is preferably present in an amount of from 0.3 to 3 wt.%, more preferably from 0.5 to 2 wt.%.
  • the basil oil is preferably present in an amount from 0.3 to 2 wt.%, based on the total weight of the composition, more preferably from 0.5 to 1 wt.%.
  • the limonene and the thymol are present in a weight ratio of limonene to thymol of from 1:2 to 3:1, more preferably from 1:1 to 2.5:1, and most preferably from 1.5:1 to 2:1.
  • the thymol and the basil oil, the monoterpenoid selected from geraniol and 1,8- cineole, or the combination thereof are present in a weight ratio of thymol to monoterpenoid of from 1:2 to 10:1, more preferably from 1:1 to 6:1.
  • the composition comprises geraniol
  • the thymol and the geraniol are preferably present in a weight ratio of thymol to geraniol of from 1 :2 to 2:1, more preferably from 0.8:1 to 1.2:1.
  • composition comprises 1 ,8-cineole
  • thymol and the 1 ,8-cineole are preferably present in a weight ratio of thymol to 1 ,8-cineole of from 2:1 to 6:1, more preferably from 4:1 to 6:1.
  • composition comprises basil oil
  • the thymol and the basil oil are preferably present in a weight ratio of thymol to basil oil of from 1:1 to 5:1 , more preferably from 2:1 to 5:1.
  • the limonene and the basil oil, geraniol, 1,8-cineole, or the combination thereof are present in a weight ratio of limonene to basil oil, geraniol, 1 ,8-cineole, or the combination thereof, of from 1:2 to 15:1, more preferably from 1.5:1 to 12:1.
  • the composition comprises geraniol
  • the limonene and the geraniol are preferably present in a weight ratio of limonene to geraniol of from 1 :2 to 3:1, more preferably from 1 :1 to 2:1, and most preferably from 1.4:1 to 1.8: 1.
  • the composition comprises 1 ,8-cineole
  • the limonene and the 1 ,8- cineol are preferably present in a weight ratio of limonene to 1,8-cineol of from 5:1 to 15:1 , more preferably from 8:1 to 12:1.
  • the composition comprises basil oil
  • the limonene and the basil oil are preferably present in a weight ratio of limonene to basil oil of from 1 : 1 to 10:1, more preferably from 2:1 to 7:1, most preferably from 3:1 to 6:1.
  • the thymol, limonene, geraniol, 1 ,8-cineole, and basil oil are all essential oil components, that is, they can be obtained from essential oils, such as those listed above.
  • the essential oil components used in the present invention are obtained from essential oils (as opposed to being produced synthetically), they may be extracted from the essential oil before being incorporated into the insect control composition.
  • the composition may comprise the essential oil itself.
  • the discontinuous oil phase consists of: thymol; limonene; and basil oil, geraniol, and/or 1 ,8-cineole, preferably basil oil; or the essential oils from which the thymol, limonene and basil oil, geraniol and/or 1,8-cineole are obtained.
  • the composition comprises no essential oil components other than the thymol, limonene, and basil oil, geraniol, and/or 1,8-cineole, or the essential oils from which the thymol, limonene, and basil oil, geraniol, and/or 1,8-cineole are obtained.
  • the insect control composition further comprises a non-ionic surfactant.
  • the non ionic surfactant is present in an amount of at least 10 wt.% by weight of the composition, more preferably from 15 to 30 wt.%, and most preferably from 18 to 22 wt.%.
  • the non-ionic surfactant may be incorporated into the discontinuous oil phase and/or the continuous aqueous phase, but is preferably incorporated into the discontinuous oil phase.
  • the present inventors have found that the combination of essential oil components described herein (thymol, limonene, and basil oil, geraniol and/or 1,8-cineole), in combination with a non-ionic surfactant, is able to form a physically stable oil-in-water dispersion having high insecticidal activity, particularly against mosquito larvae and mosquito pupae. While thymol, limonene, basil oil, geraniol and 1 ,8-cineole are all individually known to have insecticidal activity, the present inventors have discovered a synergy between these actives that was hitherto unknown.
  • the actives surprisingly retain their insecticidal activity, particularly larvicidal activity, in the presence of a non-ionic surfactant.
  • a non-ionic surfactant influences the wettability of the larvae surface, facilitating the incorporation of the essential oil components into the larvae.
  • the non-ionic surfactant preferably is or comprises a fatty acid ester of a sugar, a fatty acid ester of a polyoxyalkylenated sugar, or a combination thereof.
  • the sugar is sorbitan and/or the fatty acid is oleic acid.
  • the polyoxyalkylenated sugar is a polyoxyethylenated sugar.
  • the polyoxyalkylenated sugar comprises from 10 to 30 alkoxy groups, more preferably from 15 to 25.
  • An exemplary fatty acid ester of a sugar is sorbitan monooleate, such as Span® 80 (from Croda Industrial Chemicals).
  • An exemplary fatty acid ester of polyoxyalkylenated sugar is a polyoxyethylene sorbitan monooleate such as polyoxyethylene (20) sorbitan monooleate, also known as polysorbate-80 or Tween® 80 (from Sigma Aldrich).
  • the non-ionic surfactant of the present invention is or comprises polyoxyethylene (20) sorbitan monooleate.
  • the non-ionic surfactant has a hydrophilic-lipophilic balance (HLB) of at least 14, preferably as determined by Griffin’s method.
  • HLB hydrophilic-lipophilic balance
  • the non-ionic surfactant is preferably a high-HLB surfactant.
  • Tween-80 for instance, has an HLB of 15.0.
  • the preferred non-ionic surfactants of the present invention are useful in providing a physically stable oil-in-water dispersion of the essential oil components described herein.
  • the inclusion of these surfactants has surprisingly been found to assist in maintaining or enhancing the larvicidal activity of the essential oil components in the formulation.
  • the continuous aqueous phase of the insect control composition comprises water and, optionally, a polar water-miscible liquid.
  • the polar water- miscible liquid is selected from the group consisting of C1-C4 alcohols, polyethylene glycol, ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, glycerol, diethylene glycol mono ethyl ether, propylene carbonate and mixtures of two or more thereof.
  • the polar water-miscible liquid acts as a co-surfactant, which helps to form and stabilise the oil-in-water dispersion.
  • the polar water-miscible liquid is or comprises one or more C1-C4 alcohols, more preferably ethanol, isopropanol and/or butanol. Most preferably, the polar water-miscible liquid is or comprises isopropyl alcohol.
  • the water is present in an amount of at least 25 wt.% by weight of the composition, more preferably from 30 to 60 wt.%.
  • the polar water-miscible liquid, where present, is preferably present in an amount of from 5 to 50 wt.% by weight of the composition, more preferably from 15 to 35 wt.%.
  • the composition further comprises one or more additives, such as antioxidants, colourants and/or bitterants.
  • additives such as antioxidants, colourants and/or bitterants.
  • the composition further comprises between 0.05 to 1 wt.% of an inorganic sodium salt by weight of the composition, preferably between 0.1 to 0.5 wt.%, more preferably between 0.15 to 0.25 wt.%, even more preferably about 0.2 wt.%; wherein preferably the inorganic sodium salt is selected from the group consisting of bicarbonate, sodium carbonate, sodium phosphate, sodium polyphosphate, and combinations thereof, most preferably wherein the inorganic sodium salt is sodium bicarbonate.
  • compositions comprising an inorganic sodium salt remain stable for at least 2 years. This can be translated into a longer shelf life of the compositions.
  • the composition consists essentially of or consists of the aforementioned components (that is, the discontinuous oil phase, the continuous aqueous phase, the non ionic surfactant and, where present, the one or more additives), preferably in the aforementioned amounts.
  • the composition is in the form of an oil-in-water dispersion.
  • the composition is in the form of an emulsion.
  • the emulsion may be in the form of a macroemulsion or a microemulsion.
  • Macroemulsions are distinct from microemulsions in that they have a larger mean oil droplet diameter.
  • macroemulsions are thermodynamically unstable. As a result of this relative thermodynamic instability, macroemulsions are typically prepared in a different manner from microemulsions.
  • the composition is in the form of a microemulsion, preferably having a mean oil droplet diameter (D 4, 3) of from 1 to 100 nm.
  • droplet diameter is measured by use of a Malvern Mastersizer 2000 laser diffraction particle size analyser.
  • Microemulsions due to their small mean oil droplet size and low interfacial intension, are recognized as a very good delivery system of oils.
  • Natural oil based microemulsion technology could provide a very potent mode for making insect repellants and killing products.
  • the combinations of essential oil components and non-ionic surfactants described herein have been found to provide physically stable microemulsions having excellent larvicidal activity.
  • the insect control composition kills at least 90%, more preferably at least 95%, and most preferably 100% of mosquito larvae when tested under the conditions used in the Examples.
  • the insect control composition preferably kills at least 90%, most preferably at least 95% and most preferably 100%, of late third instar or early fourth instar mosquito larvae of Culex quinquefasciatus within 24 hours of being applied to the larvae, preferably as a 1:4000 dilution in water.
  • the insect control composition most preferably fills at least 90%, more preferably at least 95% and most preferably 100%, of late third instar or early fourth instar mosquito larvae of Culex quinquefasciatus and/or Aedes aegypti within 4 hours of being applied to the larvae, preferably as 1 :3000 dilution in water.
  • the insect control composition is physically stable for at least 3 months at 30 °C, as measured at 75% Relative Humidity (RH), more preferably for at least 6 months, and most preferably for at least 12 months.
  • RH Relative Humidity
  • the stability is measured after storage in a closed, airtight container.
  • the present invention provides an insect control composition in the form of a microemulsion comprising a continuous aqueous phase, a discontinuous oil phase and from 15 to 30 wt.% of a non-ionic surfactant by weight of the composition, wherein the discontinuous oil phase comprises: thymol, limonene; and basil oil, geraniol, 1,8-cineole or a combination thereof, preferably basil oil wherein the non-ionic surfactant is a polyoxyalkylene sugar monooleate having a HLB of at least 14, wherein the thymol, limonene and basil oil, geraniol, 1 ,8-cineole, or combination thereof, are present in amounts, by weight of the composition, of from 2 to 4 wt.%, from 2 to 8 wt.% and from 0.5 to 5 wt.% respectively, wherein the limonene and the thymol are present in a weight ratio of limonene to th
  • the present invention provides a bottle comprising an insect control composition as defined in relation to the first or second aspect.
  • the bottle is a screw cap bottle.
  • the bottle is a spray bottle, preferably a trigger spray bottle.
  • the present invention provides a method for killing or repelling insects comprising applying to the insects or to a target site of insect activity or infestation an insect control composition as defined in relation to the first aspect.
  • the insects are mosquitoes.
  • the insects are preferably mosquito larvae or mosquito pupae.
  • the method kills at least 90%, more preferably at least 95%, and most preferably 100% of insects (such as mosquito larvae or mosquito pupae) that are initially present at the target site of insect activity or infestation when the composition is applied.
  • the composition may be applied to the insects or target site of insect activity or infestation in the form of a spray.
  • the method comprises: a) providing 0.1 ml_ to 5ml_ of the composition according to any of the claims 1-16, preferably 0.5ml_ to 2.5 ml_, more preferably 1ml_ to 2ml_, even more preferably about 1ml_; b) providing 1L to 10 L of water, preferably 2L to 7.5L, more preferably in 3 L to 5L, even more preferably about 3L; c) diluting the composition provided in step a) in the water provided in step b) to obtain a diluted composition; d) applying the diluted composition of step c) to insects or to a target site of insect activity or infestation.
  • the present invention provides a use of an insect control composition as defined in relation to the first aspect for killing or repelling insects.
  • the insects are mosquitoes.
  • the composition may be used to kill mosquito larvae and/or mosquito pupae, or to repel adult mosquitoes.
  • the present invention provides a method for manufacturing the insect control composition of the first aspect, the method comprising mixing: thymol; limonene; basil oil, geraniol, 1,8-cineole, or a combination thereof, preferably basil oil; a non-ionic surfactant;
  • an insect control composition comprising a continuous aqueous phase, a discontinuous oil phase and the non-ionic surfactant, wherein the discontinuous oil phase comprises the thymol, the limonene and the basil oil, geraniol, 1,8-cineole, or a combination thereof.
  • the mixing is performed at room temperature (for instance at from 20 to 25 °C).
  • the continuous aqueous phase of the composition comprises water and a polar water-miscible liquid.
  • the method preferably comprises: (i) dissolving or dispersing the non-ionic surfactant in water to form a solution or a dispersion; (ii) dissolving or dispersing the thymol, limonene and basil oil, geraniol, 1,8-cineole, or a combination thereof, in the polar water-miscible liquid to form a premix; and (iii) combining the premix with the solution or dispersion formed in step (i).
  • the method further comprises at least partially filling a bottle with the insect control composition.
  • microemulsions comprising various combinations of essential oil components and surfactants was prepared.
  • the compositions were in accordance with Compositions 1 to 14 as shown in Table 1.
  • the method used to prepare the microemulsions included the following steps:
  • step (iii) combining the premix with the clear homogeneous solution of step (i).
  • composition 14 only the composition in accordance with the present invention (Composition 14) provided both physical stability (no observed phase separation) and high bio-efficacy (100% mortality rate of mosquito larvae after 24 hours). The remaining compositions were physically unstable and/or less efficacious.
  • Table 1 Chemical compositions of microemulsions of Example 1, physical observations and bioefficacy results
  • microemulsions were prepared in accordance with the chemical compositions shown in Tables 2 to 4.
  • the microemulsions were prepared in accordance with the method of Example 1.
  • the microemulsions were also observed for physical stability and their bio efficacy was tested in accordance with the method of Example 1 , although with different dilutions of the compositions in water as shown in the tables below.
  • the physical stability of the compositions was determined by an accelerated stability study. The compositions were stored in a closed, airtight container at 55 °C for 2 weeks. A “pass” means that no phase separation or other visible changes were observed after the 2 weeks, whereas a “fail” means that phase separation was observed.
  • composition 20 Only the composition in accordance with the present invention (Composition 20) provided both physical stability (no observed phase separation) and high bio-efficacy (100% mortality rate of mosquito larvae after only 4 hours). Indeed, the bio-efficacy of Composition 20 was highest even though it was used in a far more dilute form than the remaining compositions.
  • Table 3 Chemical composition of a dual-active microemulsion of Example 2, physical observations and bio-efficacy results
  • Table 4 Chemical composition of triple-active microemulsion of Example 2, physical observations and bioefficacy results
  • compositions according to the invention are effective against disease-causing mosquito larvae.
  • These microemulsion formulations have a toxic effect on mosquito larvae of, in particular, Aedes aegypti and Culex quinquefasciatus, which are responsible for causing diseased such as dengue and malaria.
  • the present inventors have observed that the formulations according to the invention, even when applied diluted (as composition 20 of example 2), remain effective for at least one week after the application.

Abstract

The present invention relates to an insect control composition comprising a continuous aqueous phase, a discontinuous oil phase and a non-ionic surfactant, wherein the discontinuous oil phase comprises thymol, limonene and basil oil, geraniol, 1,8-cineole or a combination thereof, preferably basil oil. It further relates to a bottle comprising the composition according to the invention. It further relates to a method for killing or repelling insects and to a use of an insect control composition for killing or repelling insects. Finally, it relates to a method of manufacturing an insect control composition.

Description

Insect control composition
The present disclosure relates to an insect control composition. In particular, the present disclosure relates to an insect control composition that has high activity against mosquito larvae and pupae, while being safe to use around children and household pets.
Insect borne diseases are a serious threat to public health. Mosquitoes, for instance, are the primary carrier for parasites that cause malaria and viruses that cause dengue fever, Chikungunya, Zika and yellow fever. Several approaches have been developed for managing mosquito populations and mitigating the threat to health posed by mosquitoes. The most common approach is to use a chemical insecticide to kill mosquito larvae or pupae or to repel or kill adult mosquitoes. However, chemical insecticides can be toxic to humans and other non-target organisms. Moreover, the widespread global use of chemical insecticides has resulted in mosquitoes developing resistance to many chemical insecticides. Similar issues have been reported in relation to other insect pests, such as cockroaches.
Natural products, such as essential oils, have gained significant interest as potential vector control agents in view of their high target specificity and low toxicity towards humans and other non-target organisms. They are also friendlier to the environment than chemical insecticides and do not tend to accumulate along food chains. Several essential oils have been investigated as potential insecticides. In one study, thyme oil, catnip oil, amyris oil, eucalyptus oil and cinnamon oil were tested against mosquito larvae and as repellents against adult mosquitoes (see Zhu et al., Journal of the American Mosquito Control Association, 2006, 22(3): 515-5220). In another study, the larvicidal and repellent potential of Mentha piperita essential oil was investigated (see Kumar et al., Asian Pacific Journal of Tropical biomedicine, 2011 , 1(2): 85-88).
Developing suitable delivery vehicles for essential oils and combinations of essential oils has proven challenging. Emulsified oil-in-water product forms are desirable for use in coolers, accumulated waters, overhead tanks and the like, as well as for use in sprays, and it is believed that such formulations could provide a potent mode for making insect repellents and killing products. However, the present inventors have found that providing a physically stable formulation of certain essential oil components (that is, without phase separation) is extremely challenging. Moreover, the requirement for a surfactant can influence the interaction of the oils with the target organism. For instance, surfactants can change the wettability of mosquito larvae, affecting their ability to incorporate essential oils. Accordingly, even if an essential oil or a component thereof has known insecticidal activity, this does not necessarily mean that the insecticidal activity will be high once incorporated into a surfactant- containing oil-in-water dispersion.
There remains a need for essential oil-based oil-in-water formulations that are effective insect control agents. In particular, there is a need for essential oil-based oil-in-water dispersions having high insecticidal activity while maintaining good physical stability.
Accordingly, it is one object of the present invention to provide an environmentally friendly insect control composition having high insecticidal activity, for instance against mosquito larvae and mosquito pupae.
It is an alternative and/or additional object to provide an essential oil-based insect control composition having high insecticidal activity and good physical stability.
According to a first aspect, the present invention provides an insect control composition comprising a continuous aqueous phase, a discontinuous oil phase and a non-ionic surfactant, wherein the discontinuous oil phase comprises:
Thymol;
Limonene;, and
Basil oil, geraniol, 1,8-cineole or a combination thereof, preferably basil oil.
The present inventors have found that this combination of essential oil components (thymol, limonene, and basil oil, geraniol and/or 1,8-cineole), in combination with a non-ionic surfactant, is particularly effective at killing mosquito larvae and pupae. It has also been found that it is possible to provide aqueous dispersions of these essential oil components exhibiting high physical stability.
In a preferred embodiment the composition according to the invention comprises a continuous aqueous phase, a discontinuous oil phase and a non-ionic surfactant, wherein the discontinuous oil phase comprises: thymol, limonene; and basil oil. The present inventors have inventors have found that the combination of thymol, limonene, and basil oil; in combination with a non-ionic surfactant, provides aqueous dispersions (i.e. , the composition is diluted in water), which exhibit high physical stability and are particularly effective at killing mosquito larvae and pupae after only 4 hours.
According to a second aspect, the present invention provides a bottle comprising an insect control composition as defined in relation to the first second aspect.
According to a third aspect, the present invention provides a method for killing or repelling insects comprising applying to the insects or to a target site of insect activity or infestation an insect control composition as defined in relation to the first aspect.
According to a fourth aspect, the present invention provides a use of an insect control composition as defined in relation to the first aspect for killing or repelling insects.
According to a fifth aspect, the present invention provides a method for manufacturing an insect control composition, the method comprising mixing thymol, limonene, and basil oil, geraniol, and/or 1 ,8-cineole, a non-ionic surfactant and water to form an insect control composition comprising a continuous aqueous phase, a discontinuous oil phase and the non ionic surfactant, wherein the discontinuous oil phase comprises the thyme oil, the limonene, and the basil oil, the geraniol, and/or the 1,8-cineole.
The present invention will now be described further. In the following passages different aspects/embodiments of the invention are defined in more detail. Each aspect/embodiment so defined may be combined with any other aspect/embodiment or aspects/embodiments unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.
The present invention provides an insect control composition. By “insect control” composition, it is meant a composition capable of killing or repelling insects, such as mosquitoes, cockroaches, houseflies, fruit flies, fleas, ticks weevils, ants, aphids, billbugs and moths. Thus, the composition is preferably an insecticide or insect repellent composition. Preferably, the composition is suitable for killing mosquito larvae and/or mosquito pupae. Alternatively or in addition, the composition may be suitable for repelling adult mosquitoes. The insect control composition, when used as an insecticide, can be used in coolers, accumulated waters, or overhead tanks. Alternatively, when the insect control composition is used as an insect repellent, the composition is preferably suitable for topical application. That is, the composition is preferably suitable for direct application to a part of the human or animal body. Preferably, the composition is suitable for direct application to the skin, for example the face, scalp, feet, limbs or trunk.
The insect control composition comprises a continuous aqueous phase and a discontinuous oil phase. In other words, the composition comprises a dispersion of a discontinuous oil phase in a continuous aqueous phase. The phases are physically distinct. The continuous aqueous phase comprises water and, optionally, a polar water-miscible liquid such as those described herein. Preferably, the discontinuous oil phase is present in an amount of at least 5 wt% by weight of the composition, more preferably from 6 to 15 wt%, and most preferably from 8 to 12 wt%.
The discontinuous oil phase comprises thymol. Thymol is also known as 2-isopropyl-5- methylphenol (IPMP). It is a monoterpenoid phenol derivative of cymene, found in thyme oil. Preferably, the thymol used in the present invention is obtained from thyme oil (an essential oil), although it may alternatively be produced synthetically. Preferably, the thymol is present in an amount of from 1 to 5 wt% by weight of the composition, more preferably from 2 to 4 wt%.
The discontinuous oil phase further comprises limonene. Limonene (1-methyl-4-(prop-1-en- 2-yl)cyclohex-1-ene) is a colourless liquid aliphatic hydrocarbon classified as a cyclic monoterpene, and is the major component in the oil of citrus fruit peels. The limonene preferably is or comprises D-limonene. Preferably, the limonene used in the present invention is obtained from citrus fruit rind, for instance orange rind or lemon rind, although it may alternatively be produced synthetically. Preferably, the limonene is present in an amount of from 1 to 10 wt% by weight of the composition, more preferably from 2 to 8 wt%, and most preferably from 4 to 6 wt%.
The discontinuous oil phase further comprises basil oil, geraniol, and/or 1 ,8-cineol, preferably basil oil. Basil oil is an essential oil obtained from the basil leaves and flowering tops ( Ocinum basilicum L or sweet basil). Its main constituent (at least 70%) is methyl cinnamate.
Geraniol ((2E)-3,7-Dimethyl-2,6-octadien-1-ol) is an alcohol monoterpenoid. It is the primary component of rose oil, palmarosa oil and citronella oil. Preferably, the geraniol, where used in the present invention, is obtained from rose oil, palmarosa oil or citronella oil, although it may alternatively be produced synthetically.
1,8-cineole (1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octane, also known as eucalyptol) is a cyclic ether monoterpenoid and is the primary component of eucalyptus globulus oil. Preferably, the 1,8-cineole, where used in the present invention, is obtained from eucalyptus globulus oil, although it may alternatively be produced synthetically.
Preferably, the basil oil, the geraniol, the 1,8-cineole, or the combination thereof, is present in an amount of from 0.3 to 5 wt.% by weight of the composition, more preferably from 0.5 to 5 wt.%, most preferably from 0.5 to 4 wt.%. Where the composition comprises geraniol, the geraniol is preferably present in an amount of from 1 to 5 wt.%, more preferably from 2 to 4 wt.%. Where the composition comprises 1,8-cineole, the 1 ,8-cineole is preferably present in an amount of from 0.3 to 3 wt.%, more preferably from 0.5 to 2 wt.%. Where the composition comprises basil oil, the basil oil is preferably present in an amount from 0.3 to 2 wt.%, based on the total weight of the composition, more preferably from 0.5 to 1 wt.%.
Preferably, the limonene and the thymol are present in a weight ratio of limonene to thymol of from 1:2 to 3:1, more preferably from 1:1 to 2.5:1, and most preferably from 1.5:1 to 2:1.
Preferably, the thymol and the basil oil, the monoterpenoid selected from geraniol and 1,8- cineole, or the combination thereof are present in a weight ratio of thymol to monoterpenoid of from 1:2 to 10:1, more preferably from 1:1 to 6:1. Where the composition comprises geraniol, the thymol and the geraniol are preferably present in a weight ratio of thymol to geraniol of from 1 :2 to 2:1, more preferably from 0.8:1 to 1.2:1. Where the composition comprises 1 ,8-cineole, the thymol and the 1 ,8-cineole are preferably present in a weight ratio of thymol to 1 ,8-cineole of from 2:1 to 6:1, more preferably from 4:1 to 6:1. Where the composition comprises basil oil, the thymol and the basil oil are preferably present in a weight ratio of thymol to basil oil of from 1:1 to 5:1 , more preferably from 2:1 to 5:1. Preferably, the limonene and the basil oil, geraniol, 1,8-cineole, or the combination thereof, are present in a weight ratio of limonene to basil oil, geraniol, 1 ,8-cineole, or the combination thereof, of from 1:2 to 15:1, more preferably from 1.5:1 to 12:1. Where the composition comprises geraniol, the limonene and the geraniol are preferably present in a weight ratio of limonene to geraniol of from 1 :2 to 3:1, more preferably from 1 :1 to 2:1, and most preferably from 1.4:1 to 1.8: 1. Where the composition comprises 1 ,8-cineole, the limonene and the 1 ,8- cineol are preferably present in a weight ratio of limonene to 1,8-cineol of from 5:1 to 15:1 , more preferably from 8:1 to 12:1. Where the composition comprises basil oil, the limonene and the basil oil are preferably present in a weight ratio of limonene to basil oil of from 1 : 1 to 10:1, more preferably from 2:1 to 7:1, most preferably from 3:1 to 6:1.
It is to be understood that the thymol, limonene, geraniol, 1 ,8-cineole, and basil oil are all essential oil components, that is, they can be obtained from essential oils, such as those listed above. Where the essential oil components used in the present invention are obtained from essential oils (as opposed to being produced synthetically), they may be extracted from the essential oil before being incorporated into the insect control composition. Alternatively, the composition may comprise the essential oil itself.
Preferably, the discontinuous oil phase consists of: thymol; limonene; and basil oil, geraniol, and/or 1 ,8-cineole, preferably basil oil; or the essential oils from which the thymol, limonene and basil oil, geraniol and/or 1,8-cineole are obtained.
Preferably, the composition comprises no essential oil components other than the thymol, limonene, and basil oil, geraniol, and/or 1,8-cineole, or the essential oils from which the thymol, limonene, and basil oil, geraniol, and/or 1,8-cineole are obtained.
The insect control composition further comprises a non-ionic surfactant. Preferably, the non ionic surfactant is present in an amount of at least 10 wt.% by weight of the composition, more preferably from 15 to 30 wt.%, and most preferably from 18 to 22 wt.%. The non-ionic surfactant may be incorporated into the discontinuous oil phase and/or the continuous aqueous phase, but is preferably incorporated into the discontinuous oil phase. The present inventors have found that the combination of essential oil components described herein (thymol, limonene, and basil oil, geraniol and/or 1,8-cineole), in combination with a non-ionic surfactant, is able to form a physically stable oil-in-water dispersion having high insecticidal activity, particularly against mosquito larvae and mosquito pupae. While thymol, limonene, basil oil, geraniol and 1 ,8-cineole are all individually known to have insecticidal activity, the present inventors have discovered a synergy between these actives that was hitherto unknown. It has also been found that the actives surprisingly retain their insecticidal activity, particularly larvicidal activity, in the presence of a non-ionic surfactant. Without wishing to be bound by theory, it is believed that the non-ionic surfactant influences the wettability of the larvae surface, facilitating the incorporation of the essential oil components into the larvae.
The non-ionic surfactant preferably is or comprises a fatty acid ester of a sugar, a fatty acid ester of a polyoxyalkylenated sugar, or a combination thereof. Preferably, the sugar is sorbitan and/or the fatty acid is oleic acid. Preferably, the polyoxyalkylenated sugar is a polyoxyethylenated sugar. Preferably, the polyoxyalkylenated sugar comprises from 10 to 30 alkoxy groups, more preferably from 15 to 25. An exemplary fatty acid ester of a sugar is sorbitan monooleate, such as Span® 80 (from Croda Industrial Chemicals). An exemplary fatty acid ester of polyoxyalkylenated sugar is a polyoxyethylene sorbitan monooleate such as polyoxyethylene (20) sorbitan monooleate, also known as polysorbate-80 or Tween® 80 (from Sigma Aldrich). Most preferably, the non-ionic surfactant of the present invention is or comprises polyoxyethylene (20) sorbitan monooleate.
Preferably, the non-ionic surfactant has a hydrophilic-lipophilic balance (HLB) of at least 14, preferably as determined by Griffin’s method. In other words, the non-ionic surfactant is preferably a high-HLB surfactant. Tween-80, for instance, has an HLB of 15.0.
The preferred non-ionic surfactants of the present invention are useful in providing a physically stable oil-in-water dispersion of the essential oil components described herein. The inclusion of these surfactants has surprisingly been found to assist in maintaining or enhancing the larvicidal activity of the essential oil components in the formulation.
As mentioned above, the continuous aqueous phase of the insect control composition comprises water and, optionally, a polar water-miscible liquid. Preferably, the polar water- miscible liquid is selected from the group consisting of C1-C4 alcohols, polyethylene glycol, ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, glycerol, diethylene glycol mono ethyl ether, propylene carbonate and mixtures of two or more thereof. The polar water-miscible liquid acts as a co-surfactant, which helps to form and stabilise the oil-in-water dispersion. Preferably, the polar water-miscible liquid is or comprises one or more C1-C4 alcohols, more preferably ethanol, isopropanol and/or butanol. Most preferably, the polar water-miscible liquid is or comprises isopropyl alcohol.
Preferably, the water is present in an amount of at least 25 wt.% by weight of the composition, more preferably from 30 to 60 wt.%. The polar water-miscible liquid, where present, is preferably present in an amount of from 5 to 50 wt.% by weight of the composition, more preferably from 15 to 35 wt.%.
In some embodiments, the composition further comprises one or more additives, such as antioxidants, colourants and/or bitterants.
In a preferred embodiment, the composition further comprises between 0.05 to 1 wt.% of an inorganic sodium salt by weight of the composition, preferably between 0.1 to 0.5 wt.%, more preferably between 0.15 to 0.25 wt.%, even more preferably about 0.2 wt.%; wherein preferably the inorganic sodium salt is selected from the group consisting of bicarbonate, sodium carbonate, sodium phosphate, sodium polyphosphate, and combinations thereof, most preferably wherein the inorganic sodium salt is sodium bicarbonate.
The present inventors have observed that compositions comprising an inorganic sodium salt remain stable for at least 2 years. This can be translated into a longer shelf life of the compositions.
Preferably, the composition consists essentially of or consists of the aforementioned components (that is, the discontinuous oil phase, the continuous aqueous phase, the non ionic surfactant and, where present, the one or more additives), preferably in the aforementioned amounts.
As noted above, the composition is in the form of an oil-in-water dispersion. Preferably, the composition is in the form of an emulsion. The emulsion may be in the form of a macroemulsion or a microemulsion. Macroemulsions are distinct from microemulsions in that they have a larger mean oil droplet diameter. Moreover, unlike microemulsions, macroemulsions are thermodynamically unstable. As a result of this relative thermodynamic instability, macroemulsions are typically prepared in a different manner from microemulsions. Preferably, the composition is in the form of a microemulsion, preferably having a mean oil droplet diameter (D4,3) of from 1 to 100 nm. In the context of the present invention, droplet diameter is measured by use of a Malvern Mastersizer 2000 laser diffraction particle size analyser. Microemulsions, due to their small mean oil droplet size and low interfacial intension, are recognized as a very good delivery system of oils. Natural oil based microemulsion technology could provide a very potent mode for making insect repellants and killing products. The combinations of essential oil components and non-ionic surfactants described herein have been found to provide physically stable microemulsions having excellent larvicidal activity.
Preferably, the insect control composition kills at least 90%, more preferably at least 95%, and most preferably 100% of mosquito larvae when tested under the conditions used in the Examples. In particular, the insect control composition preferably kills at least 90%, most preferably at least 95% and most preferably 100%, of late third instar or early fourth instar mosquito larvae of Culex quinquefasciatus within 24 hours of being applied to the larvae, preferably as a 1:4000 dilution in water. The insect control composition most preferably fills at least 90%, more preferably at least 95% and most preferably 100%, of late third instar or early fourth instar mosquito larvae of Culex quinquefasciatus and/or Aedes aegypti within 4 hours of being applied to the larvae, preferably as 1 :3000 dilution in water.
Preferably, the insect control composition is physically stable for at least 3 months at 30 °C, as measured at 75% Relative Humidity (RH), more preferably for at least 6 months, and most preferably for at least 12 months. The stability is measured after storage in a closed, airtight container. By “physically stable” it is meant that the composition appears as a homogeneous liquid with no gross apparent rheological or appearance changes from t=0.
In an especially preferred embodiment, the present invention provides an insect control composition in the form of a microemulsion comprising a continuous aqueous phase, a discontinuous oil phase and from 15 to 30 wt.% of a non-ionic surfactant by weight of the composition, wherein the discontinuous oil phase comprises: thymol, limonene; and basil oil, geraniol, 1,8-cineole or a combination thereof, preferably basil oil wherein the non-ionic surfactant is a polyoxyalkylene sugar monooleate having a HLB of at least 14, wherein the thymol, limonene and basil oil, geraniol, 1 ,8-cineole, or combination thereof, are present in amounts, by weight of the composition, of from 2 to 4 wt.%, from 2 to 8 wt.% and from 0.5 to 5 wt.% respectively, wherein the limonene and the thymol are present in a weight ratio of limonene to thymol of from 1 :1 to 2.5: 1 , wherein the thymol and the basil oil, the geraniol, the 1 ,8-cineole, or the combination thereof, are present in a weight ratio of thymol to basil oil, geraniol, 1,8-cineole, or a combination thereof, of from 1:1 to 6:1 , wherein the limonene and the basil oil, the geraniol, the 1,8-cineole, or the combination thereof, are present in a weight ratio of limonene to basil oil, geraniol, 1,8- cineole, or a combination thereof, of from 1.5:1 to 12:1, wherein the continuous aqueous phase of the insect control composition comprises water and a polar water-miscible liquid, wherein the polar water-miscible liquid is isopropyl alcohol.
According to a second aspect, the present invention provides a bottle comprising an insect control composition as defined in relation to the first or second aspect. In some embodiments, the bottle is a screw cap bottle. In other embodiments, the bottle is a spray bottle, preferably a trigger spray bottle.
According to a third aspect, the present invention provides a method for killing or repelling insects comprising applying to the insects or to a target site of insect activity or infestation an insect control composition as defined in relation to the first aspect. Preferably, the insects are mosquitoes. Where the method is for killing insects, the insects are preferably mosquito larvae or mosquito pupae. Preferably, the method kills at least 90%, more preferably at least 95%, and most preferably 100% of insects (such as mosquito larvae or mosquito pupae) that are initially present at the target site of insect activity or infestation when the composition is applied. The composition may be applied to the insects or target site of insect activity or infestation in the form of a spray.
In an embodiment, the method comprises: a) providing 0.1 ml_ to 5ml_ of the composition according to any of the claims 1-16, preferably 0.5ml_ to 2.5 ml_, more preferably 1ml_ to 2ml_, even more preferably about 1ml_; b) providing 1L to 10 L of water, preferably 2L to 7.5L, more preferably in 3 L to 5L, even more preferably about 3L; c) diluting the composition provided in step a) in the water provided in step b) to obtain a diluted composition; d) applying the diluted composition of step c) to insects or to a target site of insect activity or infestation.
According to a fourth aspect, the present invention provides a use of an insect control composition as defined in relation to the first aspect for killing or repelling insects. Preferably, the insects are mosquitoes. For instance, the composition may be used to kill mosquito larvae and/or mosquito pupae, or to repel adult mosquitoes.
According to a fifth aspect, the present invention provides a method for manufacturing the insect control composition of the first aspect, the method comprising mixing: thymol; limonene; basil oil, geraniol, 1,8-cineole, or a combination thereof, preferably basil oil; a non-ionic surfactant;
- water and optionally further ingredients; to form an insect control composition comprising a continuous aqueous phase, a discontinuous oil phase and the non-ionic surfactant, wherein the discontinuous oil phase comprises the thymol, the limonene and the basil oil, geraniol, 1,8-cineole, or a combination thereof.
Preferably, the mixing is performed at room temperature (for instance at from 20 to 25 °C).
Preferably, the continuous aqueous phase of the composition comprises water and a polar water-miscible liquid. In these embodiments, the method preferably comprises: (i) dissolving or dispersing the non-ionic surfactant in water to form a solution or a dispersion; (ii) dissolving or dispersing the thymol, limonene and basil oil, geraniol, 1,8-cineole, or a combination thereof, in the polar water-miscible liquid to form a premix; and (iii) combining the premix with the solution or dispersion formed in step (i). Preferably, the method further comprises at least partially filling a bottle with the insect control composition.
The foregoing aspects may be freely combined with any of the foregoing aspects disclosed herein.
All percentages used in this disclosure are by weight unless otherwise specified.
The present invention will now be described in relation to the following non-limiting Examples.
Example 1
A series of microemulsions comprising various combinations of essential oil components and surfactants was prepared. The compositions were in accordance with Compositions 1 to 14 as shown in Table 1. The method used to prepare the microemulsions included the following steps:
(i) slowly adding the surfactant to the water under continuous stirring until a clear homogeneous solution was formed;
(ii) dissolving the essential oil components in the isopropyl alcohol to form a premix; and
(iii) combining the premix with the clear homogeneous solution of step (i).
Physical observations were made on the compositions and are shown in Table 1. The bio efficacy of each of the compositions were tested in accordance with a percentage mortality method. In particular, 25 late third instar or early fourth instar larvae of Culex quinquefasciatuswere placed in a glass beaker and an aqueous solution of each composition (0.05 ml_ composition in 200 ml_ water) was added to the beaker. The number of dead larvae was monitored over 24 hours. The method was performed in triplicate, with the average mortality percentages presented in Table 1.
As can be seen from Table 1 , only the composition in accordance with the present invention (Composition 14) provided both physical stability (no observed phase separation) and high bio-efficacy (100% mortality rate of mosquito larvae after 24 hours). The remaining compositions were physically unstable and/or less efficacious.
Figure imgf000014_0001
Table 1: Chemical compositions of microemulsions of Example 1, physical observations and bioefficacy results
Example 2
Further microemulsions were prepared in accordance with the chemical compositions shown in Tables 2 to 4. The microemulsions were prepared in accordance with the method of Example 1. The microemulsions were also observed for physical stability and their bio efficacy was tested in accordance with the method of Example 1 , although with different dilutions of the compositions in water as shown in the tables below. The physical stability of the compositions was determined by an accelerated stability study. The compositions were stored in a closed, airtight container at 55 °C for 2 weeks. A “pass” means that no phase separation or other visible changes were observed after the 2 weeks, whereas a “fail” means that phase separation was observed.
The results are shown in Tables 2 to 4. Only the composition in accordance with the present invention (Composition 20) provided both physical stability (no observed phase separation) and high bio-efficacy (100% mortality rate of mosquito larvae after only 4 hours). Indeed, the bio-efficacy of Composition 20 was highest even though it was used in a far more dilute form than the remaining compositions.
Figure imgf000015_0001
Table 2: Chemical compositions of single-active microemulsions of Example 2, physical observations and bioefficacy results
Figure imgf000016_0001
Table 3: Chemical composition of a dual-active microemulsion of Example 2, physical observations and bio-efficacy results
Figure imgf000016_0002
Table 4: Chemical composition of triple-active microemulsion of Example 2, physical observations and bioefficacy results
For the formulation shown in Table 4 and using the same dilution, similar results were obtained with Aedes aegypti larvae.
It has been shown that the compositions according to the invention, especially when provided as a microemulsion, are effective against disease-causing mosquito larvae. These microemulsion formulations have a toxic effect on mosquito larvae of, in particular, Aedes aegypti and Culex quinquefasciatus, which are responsible for causing diseased such as dengue and malaria. In addition, the present inventors have observed that the formulations according to the invention, even when applied diluted (as composition 20 of example 2), remain effective for at least one week after the application. The foregoing detailed description has been provided by way of explanation and illustration, and is not intended to limit the scope of the appended claims. Many variations in the presently preferred embodiments illustrated herein will be apparent to one of ordinary skill in the art, and remain within the scope of the appended claims and their equivalents.

Claims

1. An insect control composition comprising a continuous aqueous phase, a discontinuous oil phase and a non-ionic surfactant, wherein the discontinuous oil phase comprises: thymol, limonene; and basil oil, geraniol, 1,8-cineole, or a combination thereof, preferably basil oil.
2. An insect control composition according to claim 1, wherein the non-ionic surfactant is or comprises a fatty acid ester of a sugar, a fatty acid ester of a polyoxyalkylenated sugar, or a combination thereof.
3. An insect control composition according to claim 1 or claim 2, wherein the non-ionic surfactant is or comprises sorbitan monooleate or a polyoxyethylene sorbitan monooleate.
4. An insect control composition according to any of the preceding claims, wherein the non-ionic surfactant has a hydrophilic-lipophilic balance (HLB) of at least 14.
5. An insect control composition according to any of the preceding claims, wherein the non-ionic surfactant is present in an amount of at least 10 wt.% by weight of the composition, preferably from 15 to 30 wt.%, more preferably from 18 to 22 wt.%.
6. An insect control composition according to any of the preceding claims, wherein the limonene is D-limonene.
7. An insect control composition according to any of the preceding claims, wherein the thymol is present in an amount of from 1 to 5 wt.% by weight of the composition.
8. An insect control composition according to any of the preceding claims, wherein the limonene is present in an amount of from 1 to 10 wt.% by weight of the composition.
9. An insect control composition according to any of the preceding claims, wherein the basil oil, the geraniol, the 1,8-cineole, or the combination thereof, is present in an amount of from 0.3 to 5 wt% by weight of the composition, preferably from 0.5 to 5 wt.%, more preferably from 0.5 to 4 wt.%.
10. An insect control composition according to any of the preceding claims, wherein the limonene and the thymol are present in a weight ratio of limonene to thymol of from 1:2 to 3:1.
11. An insect control composition according to any of the preceding claims, wherein the thymol and the basil oil, the geraniol, the 1,8-cineole, or the combination thereof, are present in a weight ratio of thymol to basil oil, geraniol, 1,8-cineole, or a combination thereof of from 1:2 to 10:1.
12. An insect control composition according to any of the preceding claims, wherein the limonene and the basil oil, the geraniol, the 1,8-cineole, or the combination thereof are present in a weight ratio of limonene to basil oil, geraniol, 1 ,8-cineole, or a combination thereof of from 1 :2 to 15:1.
13. An insect control composition according to any of the preceding claims, wherein the continuous aqueous phase comprises a polar water-miscible liquid selected from the group consisting of C1-C4 alcohols, polyethylene glycol, ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, glycerol, diethylene glycol mono ethyl ether, propylene carbonate and mixtures of two or more thereof, preferably the polar water-miscible liquid is or comprises isopropyl alcohol.
14. An insect control composition according to any of the preceding claims, wherein the composition further comprises between 0.05 to 1 wt.% of an inorganic sodium salt by weight of the composition, preferably between 0.1 to 0.5 wt.%, more preferably between 0.15 to 0.25 wt.%, even more preferably about 0.2 wt.%; wherein preferably the inorganic sodium salt is selected from the group consisting of bicarbonate, sodium carbonate, sodium phosphate, sodium polyphosphate, and combinations thereof, most preferably wherein the inorganic sodium salt is sodium bicarbonate.
15. An insect control composition according to any of the preceding claims, wherein the composition is in the form of a microemulsion.
16. An insect control composition according to any of the preceding claims, wherein the non-ionic surfactant is a polyoxyalkylene sugar monooleate having a H LB of at least 14 and is present in an amount of from 15 to 30 wt.% by weight of the composition, wherein the thymol, limonene and basil oil, geraniol, 1 ,8-cineole, or combination thereof are present in amounts, by weight of the composition, of from 2 to 4 wt.%, from 2 to 8 wt.% and from 0.5 to 5 wt.% respectively, wherein the limonene and the thymol are present in a weight ratio of limonene to thymol of from 1 :1 to 2.5: 1 , wherein the thymol and the basil oil, the geraniol, the 1 ,8-cineole, or the combination thereof are present in a weight ratio of thymol to basil oil, geraniol, 1 ,8-cineole, or a combination thereof, of from 1:1 to 6:1 , wherein the limonene and the basil oil, geraniol, the 1,8-cineole, or the combination thereof are present in a weight ratio of limonene to basil oil, geraniol, 1 ,8-cineole, or a combination thereof, of from 1.5:1 to 12:1, wherein the continuous aqueous phase of the insect control composition comprises water and a polar water-miscible liquid, wherein the polar water-miscible liquid is isopropyl alcohol, and wherein the composition is in the form of a microemulsion.
17. An insect control composition according to any of the preceding claims, wherein the composition is an insecticide or insect repellent composition, preferably for killing or repelling mosquitoes.
18. A bottle comprising the composition according to any of the preceding claims.
19. A method for killing or repelling insects comprising applying to the insects or to a target site of insect activity or infestation an insect control composition according to any of the claims 1-17.
20. A method according to claim 19, wherein the method comprises: a) providing 0.1 mL to 5mL of the composition according to any of the claims 1-17, preferably 0.5mL to 2.5 mL, more preferably 1mL to 2mL, even more preferably about 1mL; b) providing 1L to 10 L of water, preferably 2L to 7.5L, more preferably in 3 L to 5L, even more preferably about 3L; c) diluting the composition provided in step a) in the water provided in step b) to obtain a diluted composition; d) applying the diluted composition of step c) to insects or to a target site of insect activity or infestation.
21. Use of an insect control composition according to any of the claims 1-17 for killing or repelling insects.
22. A method for manufacturing an insect control composition according to any of the claims 1-17, the method comprising mixing: thymol; limonene; basil oil, geraniol, 1,8-cineole, or a combination thereof, preferably basil oil; a non-ionic surfactant; and - water to form an insect control composition comprising a continuous aqueous phase, a discontinuous oil phase and the non-ionic surfactant, wherein the discontinuous oil phase comprises the thymol, the limonene and the basil oil, geraniol, 1,8-cineole, or a combination thereof.
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