WO2021150167A1 - Procédé destiné à repousser des insectes nuisibles - Google Patents

Procédé destiné à repousser des insectes nuisibles Download PDF

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Publication number
WO2021150167A1
WO2021150167A1 PCT/SG2021/050030 SG2021050030W WO2021150167A1 WO 2021150167 A1 WO2021150167 A1 WO 2021150167A1 SG 2021050030 W SG2021050030 W SG 2021050030W WO 2021150167 A1 WO2021150167 A1 WO 2021150167A1
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Prior art keywords
massoia lactone
compound
lactone
composition
massoia
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PCT/SG2021/050030
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English (en)
Inventor
Lianghui Ji
Yu Cai
Feng Guang GOH
Soon Hwee NG
Heng Zhang
Si Te NGOH
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Temasek Life Sciences Laboratory Limited
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Priority to EP21743851.4A priority Critical patent/EP4096406A1/fr
Publication of WO2021150167A1 publication Critical patent/WO2021150167A1/fr

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P17/00—Pest repellants
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION 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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
    • A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom

Definitions

  • the present invention relates to methods and compositions for repelling arthropod pests, more particularly for repelling the insect pests’ mosquitoes and flies.
  • the compositions of the invention include massoia lactone and/or a structurally related compound.
  • Mosquitoes are devastating disease vectors. They are able to transmit diseases from an infected host to another host during blood feeding that provides the female mosquitoes with the nutrient for egg production. Aedes, which is one of the genus of mosquito, are now found in all continents except for Antarctica, spreading diseases like chikungunya, dengue fever, yellow fever and Zika [Vector Borne Disease [wwwdotwhodotint/en/news- room/fact-sheets/detai l/vector-borne-diseases] .
  • Anopheles Another genus of mosquito known as the Anopheles is the vector for transmitting Malaria which accounts for more than 400,000 deaths in the world annually [Bernier UR, Kline DL, et a!., PLoS Negl Trop Dis. 2019, 13(3): e0007188]. With vector-borne diseases accounting for more than 17% of all infectious diseases, the world health organization had responded by providing strategies and guidelines for vectors control, personal protection against vectors, management of outbreaks, training in diagnosis and development of new tools.
  • insect repellent is an effective strategy to reduce mosquito bites and disease transmission.
  • the active ingredients are usually compounds such as N,N-diethyl-mefa-toluamide (DEET), citronella oil, lemon eucalyptus oil and picaridin. While DEET is still considered the ‘golden standard’ as the active compound in many commercially available mosquito repellents due to its effectiveness, it has adverse health effects like skin irritation, breathing difficulty, burning eyes and headaches [ protesty S, Clere N, Apaire-Marchais V, Faure S, Lapied B: EurJ Pharmacol.
  • the present invention provides methods of using alternative compounds and compositions for repelling arthropod pests, more preferably insect pests.
  • the bark oil of massoia tree contains several lactones, notably C10 ((R)-5,6-Dihydro-6-pentyl-2H-pyran-2-one), C12 and C14 delta-lactone with a double bond at the C2 position in the lactone ring ( Figure 1).
  • Massoia lactones are very safe to humans as it has been used extensively as a natural flavouring agent for food and beverage. It has a sweet, creamy and milky odour that is similar to that of coconut. Massoia lactone repelled mosquitoes and flies and was at least as effective as DEET in repelling mosquitoes. Moreover, the repellent effect lasted longer than that for DEET.
  • the present disclosure provides a method of repelling an arthropod pest, the method comprising contacting a subject or article with a composition comprising massoia lactone compound ((R)-5,6-Dihydro-6-pentyl-2H-pyran-2-one), a massoia lactone-like compound or mixture thereof.
  • the arthropod may be a mosquito or fly, or other pest. Pests may be selected from the group comprising ants, cockroaches, fleas, flies such as sand flies, mites, mosquitos, spiders, ticks, termites and wasps.
  • the present disclosure provides a composition for use in repelling arthropod pests, comprising at least one massoia lactone compound, a massoia lactone-like compound or mixture thereof.
  • the present disclosure provides use of massoia lactone, a massoia lactone-like compound or mixture thereof as an arthropod pest repellent.
  • the present disclosure provides use of massoia lactone, a massoia lactone-like compound or mixture thereof, in the manufacture of an arthropod pest repellent.
  • Figure 1 shows the molecular structures of compounds tested in the present disclosure.
  • FIG. 2 is a schematic diagram of a modified cage for hand assay.
  • Wiring mesh for viewing of mosquito and air exchange. 2. 10% CO2 and 90% air mixture are introduced at 3NI/min (normal liters per minute) into the cage via a fly pad placed at the top of the cage. 3. Wre mesh from screen port is replaced with cling wrap for a better view of the opposite screen port. 4. Posterior end of the cage contains an opening covered by sleeves that had been removed for illustration purposes. 5. Wire mesh of screen port is replaced with a cut out of a cloth that is soaked with the tested compound. 6. A 90 mm Petri dish cover with a cut out of 70 mm is placed over the screen port to create a gap between the cloth and the hand. 7. Filter paper covering the side of the cage facing the tester to minimize air exchange and to block the vision.
  • Figure 3 is a schematic diagram of a setup for 2-choice assay for Drosophila melanogaster repellent assay.
  • Figure 5 shows a bar graph of the results of the 2-choice trap assay.
  • Majority of female flies avoided the trap that contains massoia lactone at all concentrations tested and entered trap with solvent (grey bar).
  • Figure 6 shows bar graphs of the repellency of dose ranges of (A) DEET and (B) massoia lactone toward Ae. aegypti mosquitoes.
  • Figure 7 shows a bar graph of the repellency over time of 2% (v/v) massoia lactone and 2% (v/v) DEET evaluated by hand-based pull-push assay immediately (0 h), 2.5 h and 5 h after application.
  • Figure 8 shows a bar graph comparing repellency between massoia lactone and essential oils; eucalyptus and citronella. All tests were done with 2% (v/v) concentration in ethanol.
  • Figure 9 shows a bar graph comparing repellency between 2% (v/v) massoia lactone- ethanol and a citronella oil based commercial anti-mosquito spray.
  • Figure 10 shows bar graphs comparing the repellency of massoia lactone (ML) (A) and DEET (0.01% to 0.5%) (B) for Culex quinquefasciatus established using the hand assay.
  • article is used herein to mean an object such as a man-made product comprised of fabric or solid substrate that said pest comes in contact with or comes in close proximity to.
  • the article may include items of furniture, items of clothing and the solid substrate may be a household surface such as a window or door frame or wall.
  • the term “arthropod pest repellent” or “insect repellent' or “repellent compound” or “repellent composition” will refer to a compound or composition which deters arthropods, more particularly insects, from subjects or articles of manufacture. Most known repellents are not active poisons at all, but rather prevent damage to plants/animals or articles of manufacture by making insect food sources or living conditions unattractive or offensive. Typically, repellents are a compound or composition that can be either topically applied to the subject; or, the compound or composition is incorporated into an article to produce an insect repellent article that deters insects from the nearby 3-dimensional space in which the subject or article exists.
  • the effect of the insect repellent is to drive the insects away from or to avoid: 1.) the subject, thereby minimizing the frequency of insect “bites” to the subject; or 2.) the article.
  • Repellents may be in various forms as described herein and as understood in the art.
  • extract refers to any compound, composition or material which is extracted from a plant or part(s) thereof.
  • massoia lactone compound may be extracted from the bark oil of massoia tree ( Cryptocaria massoia).
  • massoia lactone compound may be produced by yeast fermentation and solvent-extracted from yeast cells.
  • Massoia lactone or “Massoia lactone compound” is herein defined as C10 massoia lactone with lUPAC name (R)-5,6-Dihydro-6-pentyl-2H-pyran-2-one.
  • Massoia lactone-like compound is herein defined as a compound that has structural similarities with massoia lactone.
  • the compound may contain a delta- lactone ring. Examples are shown in Figure 1.
  • C12 massoia lactone (5,6- dihydro-6-heptyl-2H-pyran-2-one)
  • C14 massoia lactone (5,6-dihydro-6-nonyl-2H- pyran-2-one) are considered as massoia lactone-like compounds.
  • pest is herein defined as an organism, usually an arthropod, which has characteristics that are regarded by humans as detrimental or unwanted, for example by biting and in some cases causing disease.
  • pest includes but is not limited to insects.
  • the pest may be selected from the group comprising ants, cockroaches, fleas, flies, mites, mosquitoes, spiders, ticks, termites, wasps and the like.
  • Mosquitoes and/or flies may represent a significant hazard in some environments.
  • subject includes both human and animal subjects and parts thereof. Typically, subjects are considered to be insect-acceptable food sources or insect-acceptable habitats. Human subjects may be vulnerable to, for example, mosquito-borne disease such as malaria, Dengue virus and Zika virus. Animal subjects include but are not limited to mammals, including household pets, livestock animals and birds that are vulnerable to insect-borne diseases and/or infestations. DETAILED DESCRIPTION OF THE INVENTION
  • the present invention relates to the identification of novel insect repelling agents based on screening of massoia lactone and compounds that are structurally similar using Ae. aegypti and Drosophila melanogaster as the model insects.
  • the present disclosure provides a method of repelling an arthropod pest, the method comprising contacting a subject or article with a composition comprising a massoia lactone compound, a massoia lactone-like compound or mixture thereof.
  • Contacting of the composition may be by way of any method known in the art including, for example, spraying, pouring, dipping, in the form of concentrated liquids, solutions, suspensions, sprays, powders or the like, formulated to deliver a composition in an effective concentration to repel an arthropod pest.
  • the pest is selected from the group comprising ants, cockroaches, fleas, flies, mites, mosquitoes, sand flies, spiders, ticks, termites and wasps.
  • the pest is an insect.
  • the pest is a mosquito or fly.
  • the mosquito may be from, for example, the Aedes genus, the Culex genus, or from the Anopheles genus.
  • Aedes species are known to transmit diseases such as Dengue and Zika
  • Culex species are known to transmit Japanese encephalitis
  • Anopheles species are known to transmit malaria.
  • the mosquito is selected from the species Ae. aegypti, the species C.
  • the fly may be a biting fly and/or may carry a disease.
  • Flies can spread diseases because they feed freely on human food and filthy matter alike.
  • the diseases that flies can transmit include enteric infections (such as dysentery, diarrhoea, typhoid, cholera and certain helminth infections), eye infections (such as trachoma and epidemic conjunctivitis), poliomyelitis and certain skin infections (such as yaws, cutaneous diphtheria, some mycoses and leprosy).
  • Biting flies may also feed on animal blood and transmit disease such as Trypanosomiasis (sleeping sickness) transmitted by the tsetse fly and Leishmaniasis transmitted by infected sand flies.
  • the subject is a human, or animal such as a household pet, livestock animal or bird.
  • the composition may be applied to a surface of, or impregnated in, an article.
  • the article is comprised of fabric or other solid substrate that said pest comes in contact with or comes in close proximity to.
  • the article may include items of furniture, items of clothing, such as bracelets, hairbands, waistbands, shoe laces, leather belts, caps and similar items, candles, air diffusers, oil diffusers, incense, tablets, and the solid substrate may be a household surface such as a window or door frame or wall or even home paints.
  • the formulation of the pest control composition can include combining the active produced in accordance with the invention with a suitable carrier or vehicular formulation appropriate to the end-use administration of the pest control composition.
  • the pest control composition may be formulated with appropriate ingredients to provide a desired form of the composition, including, without limitation, lotions, oils, creams, cosmetics, gels, spray formulations, etc.
  • the composition is formulated for topical application.
  • the composition is a foam, gel, cream, lotion, spray, patch, suspension, emulsion, microemulsion, emulsifiable concentrate or other appropriate form.
  • the composition is formulated as an aerosol or surface spray.
  • the composition comprises massoia lactone, a massoia lactone like compound or mixture thereof is at least 0.001% (v/v), 0.01% (v/v), at least 0.1% (v/v), at least 0.5% (v/v), at least 1% (v/v), at least 5% (v/v), at least 10% (v/v), at least 15% (v/v).
  • the composition comprises massoia lactone, a massoia lactone-like compound or mixture thereof in the range of 0.001 % to 15% (v/v), preferably in the range of 0.01% to 15% (v/v), 0.01% to 5% (v/v), more preferably in the range 0.05% to 2% (v/v).
  • the massoia lactone-like compound is selected from the group comprising: 5,6-dihydro-6-heptyl-2H-pyran-2-one, 5,6-dihydro-6-nonyl-2H-pyran-2-one, 6-Amy-a-pyrone, 4,6-Dimethyl-a-pyrone, 2,6-Dimethyl-y-pyrone, 2H-Pyran-2-one, 4- Hydroxy-6-methyl-2-pyrone, 4-Methoxy-6-methyl-2H-pyran-2-one, d-Valerolactone, y- Hexalactone, g-Octalactone, g-Nonanoic lactone, d-Nonalactone, d-Decalactone, Eugenol, 2-Undecanone, ethyl pyruvate, and/or cyclopentanone.
  • the massoia lactone compound is C10 massoia lactone and/or the massoia-like compound
  • the present disclosure provides a pest-repellent composition for use in repelling arthropod pests, comprising at least one massoia lactone compound, a massoia lactone-like compound or mixture thereof.
  • Liquid formulations of the composition according to any aspect of the present disclosure may be aqueous-based or non-aqueous (i.e. organic solvents), or combinations thereof, and may be employed as foams, gels, creams, lotions, sunblock, oils, gels, sprays (including aerosol and surface), suspensions, emulsions, microemulsions oremulsifiable concentrates or the like.
  • the composition according to any aspect of the present disclosure may be formulated for dispersal.
  • the composition according to any aspect of the present invention may be employed alone or in mixtures with one another and/or with such solid and/or liquid dispersible carrier vehicles as described herein or as otherwise known in the art.
  • liquid formulations of the invention it is possible to blend a massoia lactone compound, a massoia lactone-like compound or mixture thereof with commonly used adjuvants or auxiliary agents such as emulsifying or dispersing agent, spreading agent, wetting agent, suspending agent, preservative, propellant and film-forming agent.
  • adjuvants or auxiliary agents such as emulsifying or dispersing agent, spreading agent, wetting agent, suspending agent, preservative, propellant and film-forming agent.
  • Examples of the emulsifying or dispersing agents usable in the present invention include soaps, polyoxyethylene fatty acid - alcohol ethers such as polyoxyethylene oleyl ether, polyoxyethylene alkylaryl ethers such as polyoxyethylene nonylphenyl ether, polyoxyethylene fatty acid esters, fatty acid glyceride, sorbitan fatty acid esters, sulfuric esters of higher alcohols, and alkylaryl sulfonates such as sodium dodecylbenzenesulfonate;
  • examples of the spreading and wetting agents include glycerine and polyethylene glycol;
  • examples of the suspending agents include casein, gelatin, alginic acid, carboxymethyl cellulose, gum arabic, hydroxypropyl cellulose and bentonite;
  • examples of preservatives include methyl p-hydroxybenzoate, ethyl p- hydroxybenzoate, propyl phydroxy benzoate, and butyl p-hydroxybenz
  • Carriers usable in the preparation of cream formulations include hydrocarbons such as liquid paraffin, vaseline and paraffin; silicones such as dimethylsiloxane, colloidal silica and bentonite; monohydric alcohols such as ethanol, stearyl alcohol, lauryl alcohol and cetyl alcohol; polyhydric alcohols such as polyethylene glycol, ethylene glycol and glycerin; carboxylic acids such as lauric acid and stearic acid; and esters such as beeswax and lanoline.
  • hydrocarbons such as liquid paraffin, vaseline and paraffin
  • silicones such as dimethylsiloxane, colloidal silica and bentonite
  • monohydric alcohols such as ethanol, stearyl alcohol, lauryl alcohol and cetyl alcohol
  • polyhydric alcohols such as polyethylene glycol, ethylene glycol and glycerin
  • carboxylic acids such as lauric acid and stearic acid
  • esters such as beeswax
  • the massoia lactone-like compound is selected from the group comprising: 5,6-dihydro-6-heptyl-2H-pyran-2-one, 5,6-dihydro-6-nonyl-2H-pyran-2-one, 6-Amy-a-pyrone, 4,6-Dimethyl-a-pyrone, 2,6-Dimethyl-y-pyrone, 2H-Pyran-2-one, 4- Hydroxy-6-methyl-2-pyrone, 4-Methoxy-6-methyl-2H-pyran-2-one, d-Valerolactone, y- Hexalactone, g-Octalactone, g-Nonanoic lactone, d-Nonalactone, d-Decalactone, Eugenol, 2-Undecanone, ethyl pyruvate, and/or cyclopentanone.
  • the pest is selected from the group comprising ants, cockroaches, fleas, flies, mites, mosquitos, spiders, ticks, termites and wasps.
  • the pest is an insect.
  • the pest is a mosquito or fly.
  • the mosquito may be from, for example, the Aedes genus, the Culex genus, or from the Anopheles genus.
  • Aedes species are known to transmit diseases such as Dengue and Zika
  • Culex species are known to transmit Japanese encephalitis
  • Anopheles species are known to transmit malaria.
  • the mosquito is selected from the species Ae. aegypti, the species C.
  • the chemical purity of massoia lactone extract may be in various ranges.
  • the massoia lactone extract may have 0.1 to at least 95% chemical purity.
  • the concentration of agents in the composition according to any aspect of the present invention may vary widely depending upon the nature of the particular formulation, particularly whether it is a concentrate or to be used directly as known to a skilled person.
  • the concentration of massoia lactone extract in the composition may be at least about 0.001% to 50% (v/v), 0.001% to 25% (v/v), 0.001% to 15% (v/v), 0.01% to 15% (v/v), 0.01% to 10% (v/v), 0.01% to 5% (v/v) or 0.1% to 2% (v/v) depending on the formulation and application.
  • the amount of massoia lactone, a massoia lactone-like compound or mixture thereof is in the range of 0.05% to 2% (v/v).
  • the present disclosure provides use of massoia lactone, a massoia lactone-like compound or mixture thereof, for repelling an arthropod pest.
  • the arthropod pest is selected from the group comprising ants, cockroaches, fleas, flies, mites, mosquitoes, spiders, ticks, termites and wasps.
  • the arthropod pest is an insect.
  • the pest is a mosquito or fly.
  • the mosquito may be from, for example, the Aedes genus, the Culex genus, or from the Anopheles genus.
  • Aedes species are known to transmit diseases such as Dengue and Zika
  • Culex species are known to transmit Japanese encephalitis
  • Anopheles species are known to transmit malaria.
  • the mosquito is selected from the species Ae. aegypti, the species C. quinquefasciatus, the species Anopheles sinensis and the species Anopheles gambiae.
  • the amount of massoia lactone, a massoia lactone-like compound or mixture thereof is in the range of 0.001% to 15% (v/v). In some embodiments, the amount of massoia lactone is in the range of 0.01% to 15% (v/v), preferably 0.05% to 2% (v/v).
  • the present disclosure provides use of massoia lactone, a massoia lactone-like compound or mixture thereof, in the manufacture of an arthropod pest repellent.
  • the arthropod pest is selected from the group comprising ants, cockroaches, fleas, flies, mites, mosquitoes, spiders, ticks, termites and wasps.
  • the arthropod pest is an insect.
  • the pest is a mosquito or fly.
  • the mosquito may be from, for example, the Aedes genus, the Culex genus, or from the Anopheles genus.
  • Aedes species are known to transmit diseases such as Dengue and Zika, Culex species are known to transmit Japanese encephalitis, whereas Anopheles species are known to transmit malaria.
  • the mosquito is selected from the species Ae. aegypti, the species C. quinquefasciatus, the species Anopheles sinensis and the species Anopheles gambiae.
  • massoia lactone is used.
  • the Aedes aegypti (Ae. aegypti ) (Singapore strain) mosquitoes used were maintained at Temasek Life Sciences Laboratory (TLL) Arthropod facility. The strain was obtained from EHI/National Environment Agency in April 2017. Adult mosquitoes were reared in environmental chambers at 28 ⁇ 1 °C and 75 to 80% relative humidity on a 12:12 hour photoperiod. Adult mosquitoes were provided with 10% sugar solution and the larvae were fed with a mixture of ground fish food flakes (TETRAMIN®, Tetra, Spectrum Brands Pet LLC, VA, US) and dry yeast granule (2:1). Blood feedings were carried out using membrane feeding system (HEMOTEK®, Hemotek Ltd, UK) with pathogen-free mini pig blood or rabbit blood and mouse skins as the membrane.
  • HEMOTEK® Hemotek Ltd, UK
  • the Culex quinquefasciatus (Singapore strain) used were maintained at Temasek Life Sciences Laboratory (TLL) Arthropod facility.
  • the strain was obtained from EHI/National Environment Agency in Feb 2020.
  • Adult mosquitoes were reared in environmental chambers at 28 ⁇ 1 °C and 75 to 80% relative humidity on a 12:12 hour photoperiod.
  • Adult mosquitoes were provided with 10% sugar solution and the larvae were fed with a mixture of ground fish food flakes (TETRAMIN®, Tetra, Spectrum Brands Pet LLC, VA, US) and dry yeast granule (2:1).
  • Blood feedings were carried out using membrane feeding system (HEMOTEK®, Hemotek Ltd, UK) with pathogen-free rabbit blood and mouse skins as the membrane.
  • a set of at least 3 repeats, 20 females Ae. aegypti or C. quinquefasciatus mosquitoes aged 5-7 days are placed in a cage (30 cm x 30 cm x 30 cm) and allowed to acclimatize for 10 minutes prior to the start of the experiment.
  • the mosquitoes were starved for 12 hours with access only to water.
  • Female mosquitoes which exhibit host seeking behaviour were transferred from the rearing cage to the testing cage.
  • the cage (30 cm x 30 cm x 30 cm) was purchased from Bug Dorm (shopdotbugdormdotcom). It contains an opening with a sleeve for transferring of mosquitoes and two screen ports (wired screen with donut lid) on the left and right side of the cage that has a circumference of 9 cm ( Figure 2).
  • the wired screen of one screen port is replaced with cling wrap for a better view and the wired screen of the other screen port is replaced with a disc of fabric (circumference: 10 cm) that had been soaked with the test compound.
  • C10 massoia lactone was initially produced by yeast fermentation and extracted by H2SO4 hydrolysis of yeast cells followed by ethyl acetate extraction according to the methods described previously [Ji L, Ngoh ST, W02017030503 A1], incorporated herein by reference in their entirety.
  • the C10 massoia lactone was purified by fractional distillation. The solvent was removed thoroughly using a rotary evaporator (Heidolph, Germany) set at 120 °C and massoia lactone was collected by heating the residual at 200°C under a vacuum of about 20 mBar or below. A second distillation may be performed until C10 massoia lactone reached at least 95% as judged by GCMS analysis.
  • C10 massoia lactone was also purchased from Sigma-Aldrich (W374400, natural, 395%).
  • DEET 97%, SKU: D100951
  • Other compounds including DEET (97%, SKU: D100951), were purchased from Sigma- Aldrich (USA). The compounds were dissolved in 100% ethanol to make up 1 ml of solution according to the concentration stated in corresponding experiment. 1 ml of the solution was added drop-wise onto a cut out of a piece of fabric with a circumference of 10 cm. The fabric was left to dry in a fume hood for 5 minutes prior to usage or longer in the case of duration experiments. The dried fabric was placed in between the donut lid and onto the cage.
  • the number of mosquitoes landing and probing on the fabric were recorded every minute for a period of 5 minutes and the sum of landing and probing during these 5 minutes was divided by 5 to get an average.
  • the average number for the treatment was then divided by the average number for the control treatment (solvent only) to get a landing percentage.
  • the repellency is calculated by subtracting 100 percentage to this landing percentage.
  • the hand repellent assay is a rapid screening method developed to screen compounds for their mosquito repellent property. Using a human hand as the attractant, the compounds are tested for their repellent property by creating a barrier with a piece of fabric soaked with 1 ml of diluted compound of interest. Mosquitoes that land on the fabric and probe are quantified every minute for 5 minutes to account for the percentage of repellency that the compound provides.
  • the screening method allows for the study of different concentrations of the compounds and their effectiveness in repelling the mosquitoes. The effectiveness of the compound through time can also be determined with the assay.
  • Massoia lactone was also tested for repellency against Culex quinquefasciatus mosquitoes using the push-pull hand repellent assay. Our results show that massoia lactone exhibited strong repellency against Culex quinquefasciatus (Figure 10). A dosage-dependent response of Culex quinquefasciatus to massoia lactone and DEET was observed and showed Culex quinquefasciatus mosquitoes are more sensitive to the repellents than Ae. aegypti (cf. Fig. 10A and Fig. 6A). 0.5% (v/v) of massoia lactone provided 100% protection against Culex quinquefasciatus which is more effective when comparing to results from Ae. Aegypti.
  • the duration of effective repellency is an important considering factor for making a mosquito repellent.
  • 2% massoia lactone was compared to 2% of DEET in the hand-based “push-pull” repellent assay. After application onto the fabrics, the samples were left to dry under the fume hood (with constant airflow) for 5 minutes (defined as 0 h), 150 minutes (defined as 2.5 h) or 300 minutes (5 h) before repellency test.
  • 2% DEET showed 100% repellency (or protection) at 0 h, its repellency dropped to 92.3% by 2.5 h and further to 74.07% by 5 h ( Figure 7).
  • 2% massoia lactone gave 100% repellency throughout the 5 h testing period.
  • Massoia lactone-based formulation out-performed popular essential oil-based products Some essential oils have been reported to have mosquito repellent activity. The repellency of massoia lactone -ethanol was compared with eucalyptus oil and citronella oil. Both are commonly found in some repellent products. In the hand-based “push-pull” assay, 2% (v/v) eucalyptus oil only exhibits 25.56% repellency ( Figure 8). A 2% (v/v) citronella oil in ethanol showed strong repellency at 96.18% at 0 h, however, it dropped quickly to 26.21% after 2.5 h.
  • the assay consisted of 2 traps (control, various concentration of massoia lactone) placed within a 150 mm c 150 mm c 150 mm acrylic plastic cage. Each trap (cylindrical vial; 23 mm D x 72 mm H) was filled with 1 ml of apple cider vinegar as bait and stoppered with a cotton plug ( Figure 2). C10 massoia lactone was diluted to a concentration ranging from 0.5% to 50% (v/v) with ethanol absolute. 100 pi of the diluted massoia lactone was applied onto a filter paper disc (25 mm diameter with a 6 mm hole at the centre), and the ethanol was evaporated before the filter paper was placed on the cotton plug of the trap.
  • Control trap was set up similarly with just the solvent (EtOH).
  • a trimmed 200 mI pipette tip (25 mm; opening diameter: 6 mm; exit diameter: 3 mm) was inserted through both the hole of filter paper and the cotton plug to form a channel extending into the trap which the flies could enter but not leave.
  • the 2 traps were then positioned separately at opposite corners of the cage ( Figure 3). 40 - 50 females were placed in each cage and were allowed to freely choose between these 2 traps.
  • the assay was performed in the dark at 25 °C and the number of flies in and outside the traps were counted after 24 h.
  • C10 massoia lactone (ML) and its saturated derivative, d-decalactone showed excellent repellency.
  • gamma-lactone such as g-nonanoic lactone and g-octalactone showed comparable repellency at this concentration.
  • Eugenol is more similar to DEET and also exhibited strong repellent activity against Aedes aegpyti mosquitoes ( Figure 4).
  • Undecanone which resembles to the tail region of lactones, showed significant repellency.
  • Molecules with pyrone rings also showed significant repellent activity.
  • ethyl pyruvate a reported strong inhibitor of the Ae.
  • aegypti CO2 receptor in mosquito olfactory neuron [Tauxe GM, et al., Cell 2013, 155(6):1365-1379], showed weak activity. This could be due to different assay conditions and setup used for assay.
  • cyclopentanone is a strong attractant although it has the same ring structure of gamma-lactones ( Figure 1) [Tauxe GM, etal., Ce//2013, 155(6): 1365-1379] Therefore, an effective repellent molecule requires both a hexa or penta carbon/oxygen ring and an alkyl or alkene tail of at least 3 carbons. The double bond inside the ring structure appeared to play a small role, possibly through modulating boiling point to affect protection duration.
  • Massoia lactone has a boiling point of 287 °C, almost identical to DEET (288 °C). Nevertheless, C10 massoia lactone gave better repellency at 0.5-1% (v/v) ( Figure 6) and at prolonged time lapse ( Figure 7) suggesting that massoia lactone is a significantly more potent repellent for Ae. aegypti mosquitoes than DEET. As massoia lactone has a boiling point significantly higher than that of eugenol (254 °C), we consider massoia lactone is more stable than eugenol and would be a better ingredient for insect repellents as it will last longer.
  • massoia lactone [Ji L, Ngoh ST. W02017030503 A1]
  • massoia lactone has an advantage of being an environmentally-friendly and a potentially safer active ingredient for mosquito repelling formulations.
  • Massoia lactone may function as a repellent in many more insect species, including other mosquito species such as Culex and Anopheles. Indeed, in the “push-pull” hand-based assay, massoia lactone also repels Culex quinquefasciatus ( Figure 10), suggesting it likely functions as a general mosquito repellent. To see if massoia lactone could function as a repellent to other insects, we performed a repellency assay using Drosophila melanogaster. A 2-choice assay was set up ( Figure 3). Our results showed that massoia lactone displayed clear repellency against female fruit flies in a dosage-dependent manner, between 0.5% and 10% (v/v) ( Figure 5).
  • Fletcher BS Bateman MA, Hart NK, Lamberton JA: Identification of a fruit fly attractant in an Australian plant, Zieria smithii, as O-methyl eugenol. Journal of Economic Entomology 1975, 68(6): 815-816. 4. Hao H, Wei J, Dai J, Du J: Host-seeking and blood-feeding behavior of Aedes albopictus (Diptera: Culicidae) exposed to vapors of geraniol, citral, citronellal, eugenol, or anisaldehyde. J Med Entomol. 2008, 45(3): 533-539.
  • Ji L, Ngoh ST Methods for fermentative production of massoia lactone. In.: WIPO (PCT); 2017: WO2017030503 A1. 6. Keith S, Harper C, Ashizawa A, Williams RL, Llados F, Coley C, Carlson-Lynch
  • Tauxe GM MacWilliam D, Boyle SM, Guda T, Ray A: Targeting a dual detector of skin and C02 to modify mosquito host seeking. Cell 2013, 155(6): 1365-1379.

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Abstract

L'invention concerne des procédés et des compositions destinés à repousser les arthropodes nuisibles, plus particulièrement les moustiques et les mouches. Les compositions selon l'invention comprennent de la massoia lactone et/ou un composé de type massoia lactone. Le composé de type massoia lactone est sélectionné dans le groupe comprenant : 5,6-dihydro-6-heptyl-2H-pyran-2-one, 5,6-dihydro-6-nonyl-2H-pyran-2-one, 6-Amy-a-pyrone, 4,6-diméthyl-a-pyrone, 2,6-diméthyl-y- pyrone, 2H-pyran-2-one, 4-hydroxy-6-méthyl-2-pyrone, 4-méthoxy-6-méthyl-2H-pyran-2-one, δ-valérolactone, y-hexalactone, y-octalactone, γ-nonanoïque lactone, δ-nonalactone, δ-décalactone, eugénol, 2-undécanone, éthyl pyruvate et/ou cyclopentanone.
PCT/SG2021/050030 2020-01-21 2021-01-20 Procédé destiné à repousser des insectes nuisibles WO2021150167A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023227811A1 (fr) * 2022-05-24 2023-11-30 Consejo Superior De Investigaciones Científicas (Csic) Composition attractive pour les mouches
WO2024084006A1 (fr) * 2022-10-21 2024-04-25 Firmenich Sa Compositions pour lutter contre les arthropodes

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013165477A1 (fr) * 2012-05-02 2013-11-07 Bedoukian Research, Inc. Lutte contre les moustiques et répulsion des moustiques
WO2014028835A2 (fr) * 2012-08-17 2014-02-20 Olfactor Laboratories Incorporated Compositions et méthodes pour attirer et repousser les insectes
WO2014144685A2 (fr) * 2013-03-15 2014-09-18 The Regents Of The University Of California Procédés pour l'identification de répulsifs et d'attractifs pour arthropodes, et composés et compositions identifiés pour de tels procédés
WO2015063238A1 (fr) * 2013-11-04 2015-05-07 Wageningen Universiteit Compositions insectifuges et procédés d'utilisation
WO2018140718A1 (fr) * 2017-01-27 2018-08-02 Bedoukian Research, Inc. Formulations permettant de lutter contre et de repousser les arthropodes piqueurs

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013165477A1 (fr) * 2012-05-02 2013-11-07 Bedoukian Research, Inc. Lutte contre les moustiques et répulsion des moustiques
WO2014028835A2 (fr) * 2012-08-17 2014-02-20 Olfactor Laboratories Incorporated Compositions et méthodes pour attirer et repousser les insectes
WO2014144685A2 (fr) * 2013-03-15 2014-09-18 The Regents Of The University Of California Procédés pour l'identification de répulsifs et d'attractifs pour arthropodes, et composés et compositions identifiés pour de tels procédés
WO2015063238A1 (fr) * 2013-11-04 2015-05-07 Wageningen Universiteit Compositions insectifuges et procédés d'utilisation
WO2018140718A1 (fr) * 2017-01-27 2018-08-02 Bedoukian Research, Inc. Formulations permettant de lutter contre et de repousser les arthropodes piqueurs

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023227811A1 (fr) * 2022-05-24 2023-11-30 Consejo Superior De Investigaciones Científicas (Csic) Composition attractive pour les mouches
WO2024084006A1 (fr) * 2022-10-21 2024-04-25 Firmenich Sa Compositions pour lutter contre les arthropodes

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