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WO2024201283A1 - Compositions insecticides et arachnicides et utilisations associées - Google Patents

Compositions insecticides et arachnicides et utilisations associées Download PDF

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Publication number
WO2024201283A1
WO2024201283A1 PCT/IB2024/052873 IB2024052873W WO2024201283A1 WO 2024201283 A1 WO2024201283 A1 WO 2024201283A1 IB 2024052873 W IB2024052873 W IB 2024052873W WO 2024201283 A1 WO2024201283 A1 WO 2024201283A1
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insect
present
insects
compositions
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Michael Anthony Folan
David A. FOLAN
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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
    • A01P7/00—Arthropodicides
    • A01P7/02—Acaricides
    • 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
    • A01N25/00—Biocides, 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
    • A01N25/02—Biocides, 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
    • A01N25/04—Dispersions, emulsions, suspoemulsions, suspension concentrates or gels
    • 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
    • A01N25/00—Biocides, 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
    • A01N25/30—Biocides, 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
    • 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
    • A01N37/00—Biocides, 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
    • A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • 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
    • A01N37/00—Biocides, 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
    • A01N37/06—Unsaturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • 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
    • A01N37/00—Biocides, 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
    • A01N37/44—Biocides, 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 containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • 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
    • A01N37/00—Biocides, 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
    • A01N37/44—Biocides, 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 containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
    • A01N37/46—N-acyl derivatives
    • 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
    • A01P7/00—Arthropodicides
    • A01P7/04—Insecticides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A61K9/0017—Non-human animal skin, e.g. pour-on, spot-on
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on

Definitions

  • the scientific term ‘Arthropod’ includes Crustaceans (lobsters and crabs), Arachnids (spiders, ticks and mites), Hexapoda (Insects - fleas, midge, mosquito and horse-fly), Chilopoda and Decapoda (centipedes and millipedes).
  • Crustaceans lobsters and crabs
  • Arachnids spiders, ticks and mites
  • Hexapoda Insects - fleas, midge, mosquito and horse-fly
  • Chilopoda and Decapoda centipedes and millipedes.
  • arthropods are parasitic on plants (Caterpillar, Aphids, Locust, Mites, Weevils and Whitefly) causing serious economic damage to crop yields.
  • Arthropods that are vectors for infectious disease in human and non-human animals are mainly but not exclusively restricted to midge (e.g. Culicoides greatctatus), mosquito (e.g. Aedes aegypti) , hose-fly (Tabanidae), ticks (e.g. Ixodes Ricinus) and fleas (e.g. Ctenocephalides canis) although other parasitic insects including body lice (e.g. Pediculus humanis) and mites (e.g. Trombiculidae autumnalis and Sarcoptes scabiei) also present a significant health concern. It should be appreciated that the examples given are indicative and that there are a very large number of different species within each category - there are over 112 different species of Mosquito and some 1,350 different species of flea.
  • Arthropod borne diseases are caused by a variety of pathogens, including viruses, bacteria, fungi, and parasites (including protozoa, helminths, and ectoparasites) many of which present serious health concerns in many parts of the world and for many of these there are few safe, effective and affordable interventions.
  • Tularemia is a bacterial disease (Francisella tularensis) transmitted to humans and non-human animals by horse-fly bite, the same insect is noted for transmission of the parasitic worm, Loa loa, and other pathogens such as equine infectious anaemia, anthrax and trypanosomes (trypanosoma/Chagas).
  • Ticks are recognised as the most prodigious vectors for human and non-human animal disease including but not limited to Lyme disease (Borreliosis), Tick Borne Encephalitis, Alkhurma Haemorrhagic Fever, Colorado Tick Fever, Babesiosis, Crimean-Congo Haemorrhagic Fever, Human Granulocytic Anaplasmosis, Ricketsiosis and Tick-Borne Relapsing Fever among the most notable.
  • Lyme disease Boorreliosis
  • Tick Borne Encephalitis Alkhurma Haemorrhagic Fever
  • Colorado Tick Fever Colorado Tick Fever
  • Babesiosis Crimean-Congo Haemorrhagic Fever
  • Human Granulocytic Anaplasmosis Ricketsiosis and Tick-Borne Relapsing Fever among the most notable.
  • Hematophagous organisms that bite mammalian skin do so to feed on fresh blood and they achieve this by incising the skin with specialised cutting mouth parts and inserting a feeding tube through which blood is sucked. They act as vectors for a great variety of pathogens, including viruses, bacteria, fungi, and parasites (including protozoa, helminths, and ectoparasites).
  • pathogens including viruses, bacteria, fungi, and parasites (including protozoa, helminths, and ectoparasites).
  • Insect saliva collected into immersion oil appears as discrete aqueous droplets which may be separated by centrifugation, pooled, and components separated and identified by GC, HPLC, mass spectrometry and nuclear magnetic resonance techniques.
  • the above referenced Journal paper provides good descriptions of the myriad of components that have been isolated and their purported biological activity. It should be noted however that nearly all of the identified components are proteinaceous in nature and by definition, mostly water soluble. It is important to appreciate that any amphipathic or hydrophobic components of insect saliva will partition into the immersion oil from where they cannot be recovered without extensive solvent fractionation techniques which are not reported in current journals. Because of potential phase partitioning of lipophilic components it is likely that current understanding of the insect salivary components is incomplete.
  • insect saliva may also contain lipids, phospholipids, triglycerides and liposomal vesicles which are currently unrecognised, and which may contribute significantly to mammalian physiological response to insect saliva.
  • mast cells and dendritic cells located in the dermis at the bite site.
  • mast cells de-granulate releasing a range of locally active inflammatory agents (bradykinin and histamine) and chemoatractants (chemokines and leukotrienes) that recruit blood borne innate immune cells (neutrophils and monocytes) to the bite site.
  • chemokines and leukotrienes chemokines and leukotrienes
  • Insect saliva contains a range of active components which disrupt, suppress and frustrate the normal immune reaction described above ( L. Simo et. al. The Essential Role of Tick Salivary Glands and Saliva in Tick Feeding and Pathogen Transmission: Frontiers in Cellular Infection Microbiology. Review, 22 June 2017).
  • Sialokinin an insect tachykinin like component in mosquito saliva has been shown to cause rapid reduction in blood vessel barrier effect causing vascular leakage which enables enhanced saliva borne arbovirus infection (Lefteri D. A. et. al. PNAS Research Article, Microbiology, 2022, Vol 119, No 24.)
  • Chemical insecticides are the mainstay of commercial crop protection because they are relatively cheap, effective and frequently long lasting. Chemical insecticides fall into 3 categories - inorganic, organic or synthetic and may be further classified according to mode of action and whether they are inhaled, ingested or absorbed through the body surface of the target insects. Inhaled insecticides are mainly used to fumigate stored crops or seeds and include hydrogen cyanide, naphthalene and nicotine. Ingested insecticides are used to treat plants subject to being eaten by caterpillars for example and these include the arsenicals (copper, lead and calcium arsenite) and fluorine compounds such as sodium fluoride and cryolite. Contact insecticides include the naturally occurring nicotine, pyrethrum, derris root and fractions of petroleum distillation.
  • Chlorinated hydrocarbons of which DDT was the first and most notorious, others include lindane, Aldrin, Dieldrin and chlordane. These are all chemicals noted for their long-lasting effect, i.e. persistence in the environment.
  • Organophosphates of which Malathion and Parathion are notable examples, are chemicals designed to be absorbed into the plant from where they are poisonous to insects (mainly mites and aphids) that suck on the plant sap.
  • Carbamates such as Carbamyl and Carbofuran are chemicals noted for their rapid elimination from human and animal tissue despite which their toxicity has resulted in them being banned in many countries.
  • the carbamate mode of action and toxicity is similar to the organophosphates which is nerve paralysis due to inhibition of the enzyme cholinesterase.
  • Synthetic pyrethroids include Permerthrin, Deltamethrin and Cypermethrin all of which are commonly incorporated into products to treat head and body lice, fleas and mite infestation in humans as well as insecticidal sprays for domestic use against flies, beetles, and cockroaches.
  • Synthetic Pyrethroids are known to be toxic, they act on voltage gated sodium channels in nerves causing an influx of sodium and permanent depolarisation.
  • Formulations to counteract arthropod borne disease in humans are almost exclusively based on repellents designed to be applied to skin and clothing which are intended to prevent insect bites on exposed areas treated with the repellent, examples include the following:
  • the synthetic chemical DEET (diethyltoluamide) is considered to be the most effective repellent and is widely used in skin sprays, lotions and even sunscreens to prevent insect bites, it causes discolouration of clothing.
  • Picaridin is a chemical derived from peppers which has broad spectrum effects combined with low toxicity, it is claimed that it does not damage clothing.
  • BioUD is an extract of wild tomato consisting primarily of 2-undecanone it is promoted as an effective alternative to DEET
  • IR3535 is a synthetic chemical (Ethyl Butylacetylaminopropionate) which is reported to offer similar repellent effects as DEET against a wide range of hematophagous insects.
  • Oil of Lemon Eucalyptus is a natural extract which is promoted as an insect repellent and analgesic it is reported to be effective against a wide range of hematophagous insects.
  • Permerthrin for example is a synthetic pyrethroid which together with similar neurotoxic Insecticidal agents (deltamethrin and Cypermethrin) is used to treat human head lice and scabies, it is known to cause skin rash and irritation and is classified by the US EPA as a carcinogen. Efficacy of all of the pyrethroids is being reduced by a phenomenon known as ‘knockdown resistance’ in insects whereby insects become resistant to these neurotoxic agents.
  • the present invention is a composition comprising an emulsion or a reactive emulsion which comprises a) an effective amount of one or more saturated or unsaturated free fatty acids having from 4 to 22 carbon atoms or an acceptable salt or ester thereof; b) one or more membrane lipids or a hydrolysed derivative thereof, as an emulsifying agent for the free fatty acid(s), or the salt or ester thereof; and c) a diluent or carrier; wherein the fatty acid and membrane lipid together form droplets suspended within the composition, wherein the mean droplet size is less than 1 micron.
  • the present invention is an insecticidal and/or arachnidicidal composition
  • the present invention is a method for the control of insects and/or arachnids, the method comprising contacting said insects and/or arachnids, or a locus at which control is desired, with an effective amount of a composition as described herein.
  • the present invention is a method of treating and/or preventing a physiological and/or an immunological response in a subject in need thereof, wherein said physiological and/or an immunological response is caused by a bite or a sting from an insect and/or arachnid, the method comprising contacting said insects and/or arachnids, said subject, or a locus at which treatment and/or prevention is desired, with a therapeutically effective amount of a composition as described herein.
  • compositions and emulsions of the present invention have unexpected antiparasitic, insecticidal, and/or arachnidicidal effects.
  • an “Insect” is a class of very small animal with six legs, a body divided into three parts and optionally two pairs of wings including, among others, flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, bee, wasp, hornet, sawfly, ant, caterpillar, aphid, locust, weevil, beetle, whitefly, thrip, scale, earwig, caspid, or mealybug.
  • An insecticide as used herein is a compound or composition useful for the control of insects
  • an “Arachnid” is a class of joint-legged invertebrate animals (arthropods), including, among others, spider, scorpions, tick, mite, pseudoscorpion, harvestmen, camel spider, whip spider or vinegaroon.
  • An Arachnidicide as used herein is a compound or composition useful for the control of arachnids.
  • an Acaricide is a compound or composition useful for the control of acari.
  • a “Parasite” is an organism that lives in or on an organism of another species (its host) and/or benefits by deriving nutrients at the host’s expense.
  • protozoa protozoa
  • helminths helminths
  • ectoparasites an Antiparasitic is a compound or composition useful for the control of parasites.
  • a “Mollusk” is any of a large phylum of invertebrate animals (as snails, clams, and octopuses) with a soft body lacking segments and usually enclosed in a shell.
  • Control includes repelling, disabling, immobilizing, incapacitating, paralyzing, crippling, modifying behaviour, rendering moribund, and/or killing, for example a mollusk, parasite, insect and/or arachnid.
  • Phathogen includes viruses, bacteria, fungi, and parasites (including protozoa, helminths, and ectoparasites).
  • the term “Microbe” is a microorganism of microscopic size, which may exist in its single-celled form or as a colony of cells examples include but are not limited to bacteria, yeast, fungi and viruses. Many pathogens are microbes. As used herein an Antimicrobial is a compound or composition useful for the control of microbes.
  • the present invention is an antimicrobial, antiparasitic, insecticidal and/or arachnidicidal composition
  • the present invention is an insecticidal and/or arachnidicidal composition
  • composition As used herein the terms “antimicrobial, antiparasitic, Insecticidal and/or Arachnidicidal composition” and “Composition” are used interchangeably and refer to the compositions of the present invention comprising emulsions or reactive emulsions of the present invention as described herein, and optionally further comprising a diluent or carrier.
  • the present invention is a composition for use in the control of microbes, parasites, mollusks, insects, and/or arachnids. In one embodiment, the present invention is a composition for use in the control of insects, and/or arachnids. In one embodiment, the present invention is a composition for use in the control of microbes, parasites, mollusks, insects, and/or arachnids at a locus.
  • the present invention is a composition for use in the control of mollusks, insects, and/or arachnids at a locus.
  • the present invention is a composition for use in the control of microbes, parasites, mollusks, insects, and/or arachnids at a locus, wherein the locus is a plant or a subject.
  • the present invention is a composition for use in the control of mollusks, insects, and/or arachnids at a locus, wherein the locus is a plant or a subject.
  • the present invention is a composition for use in the control of insects, and/or arachnids.
  • the present invention is a composition for use in the control of insects, and/or arachnids at a locus.
  • the present invention is a composition for use in the control of insects, and/or arachnids at a locus, wherein the locus is a plant or a subject.
  • the present invention is a composition for use in the control of insects and/or arachnids on a plant.
  • the plant is a feed crop (fruit, vegetable or grain), forage crop (grasses), fiber crop (cotton, hemp or flax), oil crop (canola, olive, soybean or corn), ornamental crop (flowers, hedges, trees), or industrial crop (rubber or tobacco).
  • the present invention is a composition for use in the control of insects and/or arachnids on a subject.
  • the subject is a human or non-human animal. In one embodiment of the present invention, the subject is a mammal. In one embodiment, the mammal is a human or non-human mammal. In one embodiment, the mammal is a human. In one embodiment of the present invention, the non-human animal is a household pet, farm animal or zoo animal.
  • the non-human animal is a dog, cat, mouse, rat, gerbil, ferret, hamster, bird, horse, pony, donkey, mule, lama, alpaca, emu, sheep, goat, pig, cow, bull, steer, heifer, deer, tiger, cheetah, wolf, monkey, lion, bear, fox, gorilla, or kangaroo.
  • the subject is not a parasite or arthropod.
  • the subject is a household pet, such as, a dog, cat, bird, rat, mouse, ferret, gerbil or hamster.
  • the subject is a farm animal, such as, a horse, pony, donkey, mule, lama, alpaca, emu, pig, bird, cow, bull, steer, heifer, sheep, or goat.
  • the subject is a zoo animal, such as, bird, deer, tiger, cheetah, wolf, monkey, lion, bear, fox, gorilla, or kangaroo.
  • the compositions of the invention control an insect and/or arachnid upon contact. Without wishing to be bound by theory, it is believed that on contact with an insect, and/or arachnid, the compositions of the present invention rapidly penetrate the natural orifices including the mouth, anus and/or spiracles, physically blocking the insect and/or arachnid’s essential physiological processes and controlling, for example, incapacitating and/or killing the insect and/or arachnid.
  • Contact includes the insect and/or arachnid attending a locus comprising compositions of the present invention and/or the compositions of the present invention being applied directly to the insect and/or arachnid.
  • the compositions are contacted with a locus prior to infestation by insects and/or arachnids to prevent insects and/or arachnids infesting said locus.
  • the locus is a subject, such as a human or non-human animal.
  • the locus is a plant.
  • compositions are contacted directly with an insect and/or arachnid to treat and/or prevent infestation of a locus by said insects and/or arachnids.
  • the locus is a subject, such as a human or non-human animal. In one embodiment the locus is a plant.
  • the term “Infestation” includes where one or more arthropod, such as, an insect and/or arachnid attends a locus at which their attendance is not desired.
  • compositions are contacted with a plant and/or a locus around a plant prior to infestation by insects and/or arachnids to prevent insects and/or arachnids infesting said plant.
  • the compositions are contacted directly with an insect and/or arachnid to treat and/or prevent infestation of a plant by said insects and/or arachnids.
  • the compositions are contacted with a plant to treat and/or prevent infestation by insects and/or arachnids by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention to and/or around said plant.
  • the plant such as, a feed crop (fruit, vegetable or grain), forage crop (grasses), fiber crop (cotton, hemp or flax), oil crop (canola, olive, soybean or corn), ornamental crop (flowers, hedges, trees), or industrial crop (rubber or tobacco) or a locus around the plant is contracted with the compositions of the present invention by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe to treat or prevent infestation by insects and/or arachnids.
  • a feed crop fruit, vegetable or grain
  • forage crop grasses
  • fiber crop cotton, hemp or flax
  • oil crop canola, olive, soybean or corn
  • ornamental crop flowers, hedges, trees
  • industrial crop rubber or tobacco
  • compositions are contacted with a subject prior to infestation by insects and/or arachnids to prevent insects and/or arachnids infesting said subject.
  • the subject is a human or non-human animal.
  • compositions are contacted directly with an insect and/or arachnid to treat and/or prevent infestation of a subject by said insects and/or arachnids.
  • compositions are contacted with a subject to treat or prevent infestation by insects and/or arachnids by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention to said subject.
  • compositions of the present invention are contacted with a subject, for example, human, dog, cat, mouse, rat, gerbil, ferret, hamster, bird, horse, pony, donkey, mule, lama, alpaca, emu, sheep, goat, pig, cow, bull, steer, heifer, deer, tiger, cheetah, wolf, monkey, lion, bear, fox, gorilla, or kangaroo by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention to treat or prevent infestation by insects and/or arachnids.
  • a subject for example, human, dog, cat, mouse, rat, gerbil, ferret, hamster, bird, horse, pony, donkey, mule, lama, alpaca, emu, sheep, goat, pig, cow,
  • compositions of the present invention are contacted with a subject, for example, human, dog, cat, gerbil, ferret, hamster, horse, pony, donkey, mule, sheep, goat, pig, cow, bull, steer or heifer spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention to treat or prevent infestation by insects and/or arachnids.
  • a subject for example, human, dog, cat, gerbil, ferret, hamster, horse, pony, donkey, mule, sheep, goat, pig, cow, bull, steer or heifer spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention to treat or prevent infestation by insects and/or arachnids.
  • compositions of the present invention modify the insect and/or arachnid behaviour at a locus, for example, a plant or subject, for example, repelling the insect and/or arachnid from the plant or subject thus preventing it from eating said plant or biting said subject and/or causing the insect, and/or arachnid to release itself from said subject after biting and/or prior to completion of its blood meal and thus reducing the transmission of a pathogen to a subject.
  • a locus for example, a plant or subject
  • repelling the insect and/or arachnid from the plant or subject thus preventing it from eating said plant or biting said subject and/or causing the insect, and/or arachnid to release itself from said subject after biting and/or prior to completion of its blood meal and thus reducing the transmission of a pathogen to a subject.
  • the compositions of the present invention modify the biological mechanism that insects and/or arachnids use to anchor in a bite site of a subject. In one embodiment of the present invention, the compositions of the present invention cause insects and/or arachnids to be dislodged or to dislodge themselves from a bite site on a subject. In one embodiment of the present invention, the compositions of the present invention modify the biochemistry of a secretion from an arthropod. In one embodiment, a secretion from an arthropod includes, for example, insects and/or arachnid saliva which comprises, for example, a biochemical cement that, for example, ticks use to anchor in a bite site of a subject.
  • cement includes any secretion from an insect and/or arachnid which is or comprises a component would aid in the adhesion of the insect and/or arachnid to a bite site.
  • the insect and/or arachnid is a flea, midge, mosquito, horsefly, gnat, louse, spider, tick, or mite.
  • the insect and/or arachnid is a flea, midge, mosquito, horsefly, tick, or mite.
  • the insect and/or arachnid is a flea, midge, horsefly, tick, or mite.
  • the arachnid is a tick.
  • the invention is a composition useful for control of insects, and/or arachnids, in particular, hematophagous organisms which can act as vectors for a great variety of pathogens, including viruses, bacteria, fungi, and parasites.
  • the invention is a composition for use in treating and/or preventing a disease in a subject in need thereof, wherein said disease is caused by a pathogen transmitted to said subject by an insect, arachnid, and/or parasite the method comprising contacting said parasites, insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention.
  • the invention is a topical composition for use in treating and/or preventing a disease in a subject in need thereof, wherein said disease is caused by a pathogen transmitted to said subject by an insect, arachnid, and/or parasite comprising the method comprising contacting said insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a topical composition of the present invention.
  • the invention is a topical composition for use in treating and/or preventing a subdermal, intradermal or subcutaneous disease in a subject, wherein said disease is caused by a pathogen transmitted to said subject by an insect, arachnid, and/or parasite the method comprising contacting said insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention.
  • the disease is Anaplasmosis, Human Granulocytic Anaplasmosis, Babesiosis, Borrelia mayonii infection, Borrelia miyamotoi infection, Bourbon virus infection, Colorado tick fever, Alkhurma Haemorrhagic Fever, Ehrlichiosis, Heartland virus, Lyme disease , Powassan disease, Rickettsia parkeri rickettsiosis, Rocky Mountain spotted fever (RMSF), STARI (Southern tick-associated rash illness), Tickborne relapsing fever (TBRF), Tularemia, Rickettsiosis, Tick borne encephalitis, Akabane virus, Schmallenberg, Blue-tongue, Equine infectious anaemia, Anthrax, Trypanosomes (trypanosoma/Chagas), Malaria, Dengue, Yellow fever, Zika virus, Chikungunya, Human Lymphatic Filariasis, Black death, Plague, Bu
  • the parasite, insect and/or arachnid is flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, spider, tick, mite, scorpion, pseudoscorpion, harvestmen, camel spider, whip spider, or vinegarroon.
  • the insect is a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, or ant.
  • the Aracnhid is a spider, tick, mite, scorpion, pseudoscorpions, harvestmen or vinegaroons.
  • the flea is Tunga penetrans, chigoe, chigo, chigoe flea, chigo flea, jigger, nigua, sand flea, or burrowing flea.
  • the mite is Sarcoptes scabiei var. hominis, Trombiculidae; harvest mite, berry bug, bush-mite, red bus or scrub-itch mite.
  • the parasite is Loa Loa.
  • the invention is a composition for use in treating and/or preventing a disease in a subject in need thereof, wherein said disease is caused by a pathogen transmitted by an hematophagous organism to said subject , comprising contacting said organism, a locus at which treatment and/or prevention is desired, or said subject with a therapeutically effective amount composition of the present invention and a pharmaceutically acceptable diluent or carrier.
  • the disease is Anaplasmosis, Human Granulocytic Anaplasmosis, Babesiosis, Borrelia mayonii infection, Borrelia miyamotoi infection, Bourbon virus infection, Colorado tick fever, Alkhurma Haemorrhagic Fever, Ehrlichiosis, Heartland virus, Lyme disease , Powassan disease, Rickettsia parkeri rickettsiosis, Rocky Mountain spotted fever (RMSF), STARI (Southern tick-associated rash illness), Tickborne relapsing fever (TBRF), Tularemia, Rickettsiosis, Tick borne encephalitis, Akabane virus, Schmallenberg, Blue-tongue, Equine infectious anaemia, Anthrax, Trypanosomes (trypanosoma/Chagas), Malaria, Dengue, Yellow fever, Zika virus, Chikungunya, Human Lymphatic Filariasis, Black death, Plague, Bu
  • the parasite, insect and/or arachnid is flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, ant, spider, tick, mite, scorpion, pseudoscorpion, harvestmen, camel spider, whip spider, or vinegarroon.
  • the insect is a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, or ant.
  • the Aracnhid is a spider, tick, mite, scorpion, pseudoscorpions, harvestmen or vinegaroons.
  • the flea is Tunga penetrans, chigoe, chigo, chigoe flea, chigo flea, jigger, nigua, sand flea, or burrowing flea.
  • the mite is Sarcoptes scabiei var. hominis, Trombiculidae; harvest mite, berry bug, bush-mite, red bus or scrub-itch mite.
  • the parasite is Loa Loa.
  • the compositions of the present invention treat and/or prevent a subdermal, intradermal or subcutaneous disease in a subject.
  • compositions of the present invention are applied topically to a subject and treat and/or prevent a subdermal, intradermal or subcutaneous disease in said subject.
  • the invention is a composition for use in controlling a parasite, insect and/or arachnid and treating and/or preventing a disease in a subject transmitted to said subject by said parasite, insect and/or arachnid.
  • the invention is an insecticidal, arachnicidal, antiparasitic and/or antimicrobial composition comprising an emulsion or a reactive emulsion of the present invention as described herein.
  • the compositions of the present invention penetrates the skin of a subject and controls a pathogen, such as a parasite that may be embedded there (e.g., Trombiculidae, Sarcoptes scabiei var. hominis, Tunga penetrans) and treats and/or prevents the disease caused by said parasite (e.g., chiggers, scabies, and/or tungiasis).
  • a pathogen such as a parasite that may be embedded there (e.g., Trombiculidae, Sarcoptes scabiei var. hominis, Tunga penetrans) and treats and/or prevents the disease caused by said parasite (e.g., chiggers, scabies, and/or tungiasis).
  • the invention is a composition for use in suppressing, treating and/or preventing a subject’s physiological and/or immunological responses to a bite or a sting from an insect and/or arachnid.
  • the invention is a composition for use in suppressing, treating and/or preventing a subject’s physiological and/or immunological responses to a bite from a hematophagous organism.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to an insect and/or arachnid secretion at a bite or sting site to reduce, for example, inflammation; itchiness; erythema; hives; redness; pain; vasoconstriction; platelet aggregation; degranulation of mast cells; release of dendritic cells; activation of fibroblasts, fibrinogen, bradykinins, histamines, or chemoattractant (chemokines or leukotrienes); transport of neutrophils or monocytes; or generating antigen specific antibodies or T lymphocytes.
  • chemokines or leukotrienes chemoattractant
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a secretion of, for example, a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, , sawfly, ant, spider, tick, mite, scorpion, pseudoscorpion, harvestmen, camel spider, whip spider, or vinegarroon at a bite/sting site.
  • a secretion for example, a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, , sawfly, ant, spider, tick, mite, scorpion, pseudoscorpion, harvestmen, camel spider, whip spider, or vinegarroon at a bite/sting site.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a secretion of, for example, a flea, midge, mosquito, horse-fly, bedbug, gnat, louse, spider, tick, or mite at a bite/sting site.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a secretion of, for example, a flea, midge, mosquito, horse-fly, gnat, louse, tick, or mite at a bite site.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a secretion of, for example, a flea, midge, mosquito, horse-fly tick, or mite at a bite site.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a secretion of a tick or mite at a bite site.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a secretion of a tick a bite site.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a secretion of a mosquito at a bite site.
  • the emulsions and reactive emulsions of the present invention can be used to deliver oil soluble active ingredients, such as for example, insecticides.
  • the emulsions or reactive emulsions of the present further comprise an active ingredient.
  • the emulsions or reactive emulsions of the present further comprise an antimicrobial, antiparasitic, insecticidal and/or arachnidicidal composition.
  • the emulsions or reactive emulsions of the present further comprise an insecticidal composition. This embodiment allows for safer delivery of active ingredients including, for example, insecticides at much lower doses where potency is amplified by delivery in the emulsion or reactive emulsion of the present invention.
  • the emulsions and reactive emulsions further comprise a wetting agent in the water phase.
  • the insecticidal potency of the emulsions and reactive emulsions of the present invention is amplified by the addition of a wetting agent.
  • potency of the emulsions and reactive emulsions is increased by about 10% with the addition of a wetting agent.
  • Suitable wetting agents include glycerol, polysorbate (Tween), propylene glycol and sodium lauryl sulphate.
  • the emulsions and reactive emulsions of the present invention further comprise a wetting agent which comprises between about 0.1% and about 10%, between about 0.5% and about 5%, or between about 1% and about 5% w/w of the water phase.
  • the emulsions and reactive emulsions further comprise an amino acid derivative.
  • Suitable amino acid derivative include N-Acetyl Cysteine and/or Pyrrolidone Carboxylic Acid / Pyroglutamic Acid.
  • the emulsions and reactive emulsions of the present invention further comprise an amino acid derivative at between about 0.1% and about 10%, between about 0.5% and about 5%, or between about 1% and about 2% w/w of the water phase.
  • the emulsions and reactive emulsions further comprise N-Acetyl Cysteine and/or Pyrrolidone Carboxylic Acid / Pyroglutamic Acid.
  • the compositions of the present invention are non-toxic to a subject.
  • Non-toxic compositions includes compositions of the present invention which when contacted with a subject at the doses specified herein are not known to cause any significant adverse effect in said subject.
  • side effects encompasses unwanted and adverse effects. Side effects are always unwanted, but unwanted effects are not necessarily adverse. An adverse effect from a therapy (e.g., prophylactic or therapeutic) might be uncomfortable, harmful, or lethal.
  • Side effects include, but are not limited to fever, chills, lethargy, immunological reactions, gastrointestinal toxicities (including gastric and intestinal ulcerations and erosions), nausea, vomiting, neurotoxicities, nephrotoxicities, renal toxicities (including such conditions as papillary necrosis and chronic interstitial nephritis), hepatic toxicities (including elevated serum liver enzyme levels), myelotoxicities (including leukopenia, myelosuppression, thrombocytopenia and anaemia), dry mouth, metallic taste, prolongation of gestation, weakness, somnolence, pain (including muscle pain, bone pain and headache), hair loss, asthenia, dizziness, extra-pyramidal symptoms, akathisia, cardiovascular disturbances and sexual dysfunction.
  • gastrointestinal toxicities including gastric and intestinal ulcerations and erosions
  • nausea vomiting
  • neurotoxicities including nephrotoxicities, renal toxicities (including such conditions as papillary necrosis and chronic interstitial nephritis)
  • compositions of the present invention are biodegradable.
  • compositions of the present invention not persistent in the environment.
  • compositions of the present invention do not affect pollinating insects
  • compositions of the present invention do not present a toxic residue which might enter the human food chain.
  • compositions of the present invention are significantly safer than commercially available insecticides and pesticides.
  • the emulsions of this invention have been shown to exert minimal cytotoxicity in a wide range of cell types, they have been shown to be safe in topical and oral application, by acute I V. administration and nasal instillation. The components of these emulsions are commonly found in human foods and are safe if accidentally ingested. (Purves et. Al. J. Gen Virol 2023; 104: 001821)
  • the emulsions used in the compositions of the present invention are based on components normally found in food, and frequently used in human parenteral nutrition. As such they are infinitely safer than any of the existing chemical interventions used to protect plant, animal and human against arthropod assault.
  • the present invention is composition comprising an emulsion or a reactive emulsion of free fatty acids in de-lipidised membranes, wherein the fatty acid (oil) is surrounded by the de-lipidised membrane amphipath) in droplet form, wherein the mean droplet size is less than 1 micron, preferably in the region of between 0.8 and 0.6 micron, and preferably less than 0.5 micron.
  • the emulsion “Droplet” size refers to the size of a droplet comprising oil (fatty acid and optionally, for example, triglyceride) surrounded by/coated with de-lipidised membrane, wherein the droplet is suspended in the aqueous layer (for example, diluent carrier) of the compositions of the present invention.
  • the compositions of the present invention comprise emulsions of free fatty acids in de-lipidised membranes.
  • Emulsions of free fatty acids in de-lipidised lecithin useful in the compositions of the present invention are described in WO 2011 061237 the entire contents of which is incorporated here by reference.
  • the manufacturing methods of the emulsions described in WO 2011 061237 can be used in the preparation of the compositions of the present invention.
  • a secondary high pressure homogenisation step has been shown to greatly enhance the insecticidal and arachnidicidal activity of the emulsions used in the compositions of the present invention.
  • the enhanced manufacturing method is described in the methods section herein. Further studies of properties of the emulsions useful in the compositions of the present invention are reported in Fletcher et. Al. A Novel
  • Antiviral Formulation Inhibits a Range of Enveloped Viruses (J. General Virology 2020; 101 : pp 1090-1102), the entire contents of which is incorporated herein by reference.
  • the emulsions of the present invention are formed using homogenisation/micronization by, for example, extrusion or agitation of the lipids and fatty acids.
  • the present invention is a method of manufacturing the emulsions of the present invention, the method comprising:
  • the homogenized emulsions of the present invention with a mean droplet size of less than 1 micron show enhanced efficacy and stability versus non-homogenised emulsions.
  • an “Emulsion” is a dispersion of one immiscible liquid in an immiscible matrix. Typically emulsions are either oil in water or water in oil dispersions wherein the dispersion is prevented from coalescing by an emulsification agent which is usually amphipathic.
  • emulsion includes an oil in water or water in oil dispersion stabilised with amphipathic molecules which may be formed remotely prior to administration or In situ by administering a composition of precursors which assemble into an emulsion at the intended site of action.
  • the emulsions useful in the compositions of the present invention are based on one or a combination of oils, such as, free fatty acids selected from Caproic, Caprylic, Capric, Lauric, Undecylenic, Myristic, Palmitic, palmitoleic, Oleic, Stearic, lineic, linoleic, or linolenic, preferably Caprylic, Capric, undecylenic, lauric and Oleic and more preferably caprylic and Capric.
  • the emulsions of the present invention comprise an oil phase and a water phase. In one embodiment, the emulsions of the present invention are reactive emulsions.
  • a “reactive emulsion” is an emulsion with a depletable oil phase caused by the conversion of the free fatty acids, contained in the reactive emulsion, from oil soluble free acids to water soluble salts (soaps) when the reactive emulsion is subjected to pH change. This transition creates an amphipath with open lipophilic sites in the reactive emulsions. Having an amphipath with open lipophilic sites at a target site allows the amphipath to associate with other lipophilic surfaces such as adjacent cell membranes or an insect cuticle.
  • the reactive emulsions of the present invention create a surface phase inversion at a desired surface, allowing droplets to migrate along said inverted surface.
  • a selection of insects have a raised Tip’ around the spiracle. Where the surface of the lip remains lipophilic this lip is an impediment to aqueous phase ingress.
  • the reactive emulsions of the present invention cause surface phase inversion of a lipophilic surface causing the water repelling effect to be neutralised and/or replaced with phase attraction, thus the instant emulsion droplets can migrate over the surface, for example, the lip and into the spiracle.
  • the terms “reactive emulsion” and “emulsion” can be used herein interchangeably.
  • the presence of a free fatty acid in the emulsion facilitates phase inversion and insecticidal effect of the emulsions and reactive emulsions of the present invention.
  • the use of a free fatty acid as a depletable oil phase facilitates reactivity and delivery of an amphipath with exposed lipophilic sites and consequential surface phase inversion.
  • the ratio of free fatty acid to triglyceride can be used to control rate of reactivity.
  • the oil phase of the emulsions and reactive emulsions of the present invention comprises at least 50% the free fatty acid.
  • the oil phase of the emulsions or reactive emulsions of the present invention comprise between about 10 and about 90% fatty acid, between about 10% and about 70% fatty acid, between about 10% and about 60% fatty acid, between about 10% and about 50% fatty acid, between about 20% and about 50% fatty acid, between about 30% and about 50% fatty acid, or between about 40% and about 50% fatty acid.
  • Reduced efficacy is detectable at inclusion rates down to 10% but there is no detectable efficacy if the oil phase is 100% triglyceride and no free fatty acid.
  • Free fatty acids behave as water insoluble oils at pH values below their dissociation constant, which is normally in the region of pH 5.5. When neutralised at pH above their dissociation constant, free fatty acids become water soluble salts, and this conversion from water insoluble oil to water soluble salt is used in the emulsions of this invention to facilitate delivery of a lipophilic amphipath to a required site of action.
  • fatty acids When protonated as free acids, fatty acids are oils which may be freely dispersed in other oils and triglycerides.
  • Triglycerides are fats / oils comprising a glycerol back-bone with three fatty acids esterified to each of the three hydroxyl groups of glycerol.
  • triglycerides typically have three different esterified fatty acids.
  • Manipulation of the fatty acid composition of a tri-glyceride is achieved by chemical synthesis and so triglycerides consisting exclusively of caprylic acid are available commercially as are mixed capric / caprylic triglycerides which behave as light neutral oils.
  • Dispersion of a free fatty acid or combination thereof in triglyceride oils permits manipulation of the availability of free fatty acid and its conversion rate from free acid oil to water soluble salt which in turn affects rate of availability of de-lipidised amphipath and the anti-arthropod performance characteristics of the emulsion as described in this invention.
  • compositions of the present invention comprise an emulsion or a reactive emulsion which comprises one or more saturated or unsaturated free fatty acids having from 4 to 22 carbon atoms or a pharmaceutically acceptable salt or ester thereof; and one or more membrane lipids or a hydrolysed derivative thereof, as emulsifying agent for the free fatty acid(s) or the salt or ester thereof; and the composition further comprises a diluent or carrier.
  • the free fatty acid is selected from valeric, caproic, caprylic, pelargonic, capric, undecanoic, undecylenic, lauric, myristic, palmitic, stearic, oleic, linoleic and linolenic acids and mixtures thereof, and pharmaceutically acceptable salts and esters thereof.
  • the free fatty acid is selected from one or more of caproic, caprylic, pelargonic, capric, undecylenic and lauric acids, especially caprylic acid.
  • the free fatty acid is selected from caprylic and capric acids. In one embodiment, wherein the free fatty acid is caprylic acid.
  • the membrane lipid is selected from one or more of phospholipids, lecithin, glycerophospholipids, sphingolipids, glycosphingolipids, glycoglycerolipids and cholesterols , and hydrolysed derivatives thereof.
  • the membrane lipid is selected from one or more of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, lecithin, ceramide, sphingomyelin, glycolipids, glycosphingolipids, cerebrosides, gangliosides, glycoglycerolipids, mono-galactosyl di glyceride, lanosterol and cholesterol.
  • the membrane lipid is a phosopholipid selected from one or more of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine and lecithin, especially lecithin.
  • the membrane lipid or hydrolysed derivative thereof is de-lipidised. In one embodiment, the membrane lipid or hydrolysed derivative thereof is de-lipidised lecithin.
  • the de-lipidised lecithin contains less than 3% conjugated extraneous lipid material.
  • compositions of the present invention comprise an emulsion or a reactive emulsion which comprises a free fatty acid selected from one or more of caproic, caprylic, pelargonic, capric, undecylenic and lauric acids, in combination with de-lipidised lecithin.
  • compositions of the present invention comprise an emulsion or a reactive emulsion which comprises a weight ratio of fatty acids to membrane lipids is from about 0.25: 1 to about 10: 1 ; or from about 0.5: 1 to about 10: 1 , or from about 0.5: 1 to about 5.0: 1 , or from about 1.0: 1 to about 2.5: 1, or from about 1.25:1 to about 2.5: 1 , on a weight for weight basis.
  • compositions of the present invention comprise an emulsion or a reactive emulsion which comprises (a) one or more free fatty acids selected from the group consisting of caproic, caprylic, capric, ! auric, palmitic, stearic, oleic, linoleic and linolenic acids and mixtures thereof; and (b) one or more membrane lipids as emulsifying agent for the free fatty acid(s), wherein the membrane lipid is delipidized lecithin, wherein the weight ratio of component (a) to component (b) is from about 0.25: 1 to about 10: 1.
  • compositions of the present invention further comprise one or more pharmaceutically acceptable organic acids or a pharmaceutically acceptable salt or ester thereof; and/or one or more pharmaceutically acceptable organic acid salts.
  • the organic acid is selected from acetic, pyruvic, propionic, glycolic, oxalic, lactic, glyceric, tartronic, malic, maleic, ascorbic, fumaric, tartaric, malonic, glutaric, propenoic, cis or trans butanoic and citric acids and mixtures thereof, and pharmaceutically acceptable salts and esters thereof.
  • the organic acid is citric or lactic acid or the sodium or potassium salt thereof.
  • the organic acid salt is sodium citrate.
  • the organic acid salt is selected from sodium, potassium and calcium
  • the organic acid is a fatty acid salt which may be combined with de- lipidised lecithin formulated as a powder or paste which may be subsequently hydrated with an acidic solution causing the fatty acid salt to transition to a free acid oil spontaneously forming and emulsion with the de-lipidised lecithin as described in W02021/150501 the entire contents of which are incorporated herein by reference.
  • the emulsion is an oil-in-water emulsion.
  • the composition is formulated as a spray, aerosol, liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion, or wipe.
  • Amphipathic molecules are characterised as macromolecules with one aspect being lipophilic (oil soluble) and the opposing aspect being hydrophilic (water soluble). Such molecules are typically found in nature as membrane molecules interfacing between oil / lipid rich environments and largely aqueous environments.
  • An example of a naturally occurring amphipathic molecules are the fat globule membranes that stabilise butterfat droplets dispersed in the aqueous protein rich matrix of milk.
  • amphipaths are normally closely associated or conjugated to lipid or lipid like material, as such their lipophilic sites are fully occupied.
  • a solvent such as acetone
  • the amphipath can be suspended in an aqueous medium and when an oil is added under vigorous agitation an emulsion or a reactive emulsion will be formed with oil droplets surrounded by the amphipath, its lipophilic sites orientated into the oil and its opposing hydrophilic sites oriented into the water phase. And it should be noted that in this emulsified state the lipophilic sites of the de-lipidised amphipath are again fully occupied by the oil phase.
  • Oils used in the product of this invention must contain at least one or more free fatty acids, preferably short to medium chain saturated fatty acids and optionally these may be dispersed in a triglyceride wherein the triglyceride is no more that 60% by weight of the total oil (oil phase).
  • suitable amphipaths may be selected from lanolin, cholesterol, ceramide or lecithin, preferably lecithin may be used in the composition of the present invention.
  • Lecithin is a composition of five separate phospholipids (phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl inositol and phosphatidic acid), which may exist in different ratios depending on the source of the lecithin (soy or egg yolk are common).
  • Lecithin containing no less than 60% phosphatidyl choline and no more that 5% phosphatidic acid are preferred for this invention.
  • Delivery of a free lipophilic amphipath is achieved by using a depletable oil phase - an oil which will provisionally block the amphipath’ s lipophilic sites and subsequently free them when required by transitioning from oil to a water-soluble salt.
  • the surfactant and adhesion inhibitory properties of free fatty acid emulsions is thought to be due to the fact that free fatty acids will transition from oils to water soluble salts when subjected to a pH shift above their pKa and in doing so they expose lipophilic sites on the emulsified amphipath which are free to associate with other lipophilic sites in the immediate environment.
  • reactive emulsions of free fatty acids in de-lipidised amphipath will readily penetrate full thickness animal, such as, porcine skin and will exert an antimicrobial, insecticidal and adhesion inhibitory effect in the subcutaneous tissue. Further, as demonstrated here topical application of free fatty acid emulsions of this invention will modify the physiological response to insect bite significantly reducing erythema and the irritation (itchiness) normally associated with an insect bite.
  • Emulsions of free fatty acids in de-lipidised amphipaths as disclosed in this invention will degrade to mixtures of salts of fatty acids and de-lipidised amphipath when subjected to physiological pH values above the pKa of the fatty acid.
  • the normal pH of mammalian skin is 5.5 but subdermal pH tends towards neutrality.
  • Free fatty acid emulsions on a skin surface will remain relatively stable but when these emulsions migrate through the skin (at an insect bite site for example) they will encounter pH values which will deplete the oil phase, forming water soluble salts of free fatty acids and amphipaths with exposed lipophilic sites. These exposed lipophilic sites will readily bind to other lipophilic surfaces and/or serve as a binding site for lipophilic macromolecules in the vicinity.
  • lipophilic phase attraction is the primary physio-chemical driver for initial association between cells, including association of potential pathogens to mammalian cell surfaces and the association of biochemical ligands to specific receptor sites.
  • the present invention is a method for subdermal, intradermal, or subcutaneous suppression inhibition of a physiological and/or immunological response to insect and/or arachnid bite or sting and subdermal, intradermal, or subcutaneous suppression inhibition of the transmission of arthropod borne infectious disease.
  • Subdermal amphipaths with exposed lipophilic sites as may be generated In situ by transdermal absorption of micro-emulsions of this invention will transiently bind to lipophilic cell surfaces and in so doing will render these cells less accessible to interaction with adjacent cells and with agonist or antagonistic macromolecules in insect saliva and/or pathogens that may be contained therein.
  • Salivary inhibitors of vasoconstriction will be blocked or de-activated
  • Anti -coagulation factors will be inactivated or overcome by pro-coagulation properties of phospholipid amphipaths which mimic platelet activating factors;
  • Pathogens will be inactivated and killed before they migrate from the bite site.
  • the composition is formulated as an emulsion or a reactive emulsion, as described herein, optionally in concentrate form, incorporated and diluted in a carrier formulated as a spray, aerosol, liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe which exerts an insecticidal and/or arachnicidal effect, and which by virtue of its surfactant nature will rapidly migrate into an insect and/or arachnid bite/sting site inhibiting the infectivity of arthropod borne pathogens; modifying a subject’s physiological and/or immunological response to secretions by said insect and/or arachnid; and/or controlling said insect and/or arachnid.
  • a carrier formulated as a spray, aerosol, liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe which exerts an insecticidal and/or arachnicidal effect, and which by virtue of its
  • the present invention is a method for the control of insects and/or arachnids the method comprising contacting said insects and/or arachnids, or a locus at which control is desired, with an effective amount of a composition of the present invention.
  • the present invention is a method for the control of insects and/or arachnids at a locus the method comprising contacting said insects and/or arachnids, or said locus, with an effective amount of a composition of the present invention.
  • the locus is a plant including the locus on or around the plant.
  • the plant is a feed crop (e.g., fruit, vegetable or grain), forage crop (e.g., grasses), fiber crop (e.g., cotton, hemp or flax), oil crop (e.g., canola, olive, soybean or corn), ornamental crop (e.g., flowers, hedges, trees), or industrial crop (e.g., rubber or tobacco).
  • a feed crop e.g., fruit, vegetable or grain
  • forage crop e.g., grasses
  • fiber crop e.g., cotton, hemp or flax
  • oil crop e.g., canola, olive, soybean or corn
  • ornamental crop e.g., flowers, hedges, trees
  • industrial crop e.g., rubber or tobacco
  • the present invention is a method for control of insects, and/or arachnids on a plant the method comprising contacting said plant and/or the locus around said plant, with an effective amount of a composition of the present invention.
  • the present invention is a method for control of insects, and/or arachnids on a plant the method comprising contacting said plant and/or the locus around said plant, with an effective amount of a composition of the present invention.
  • the present invention is a method for control of insects, and/or arachnids on a plant the method comprising contacting said plant and/or the locus around said plant, with an effective amount of a composition of the present invention once, twice or more during the growing season.
  • the present invention is a method for control of insects, and/or arachnids on a plant the method comprising contacting said plant and/or the locus around said plant, with an effective amount of a composition of the present invention daily, weekly, biweekly, monthly, or annually.
  • the present invention is a method for control of insects, and/or arachnids on a plant the method comprising contacting said plant and/or the locus around said plant, with an effective amount of a composition of the present invention prior to planting the plant.
  • the insect and/or arachnid is a caterpillar, aphid, locust, weevil, beetle, whitefly, thrip, scale, earwig, capsid, or mealybug.
  • the plant, locus or insect and/or arachnid is contacted with the compositions of the present invention by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention.
  • the locus is a subject including the locus on or around the subject.
  • the subject is a human or non-human animal. In one embodiment, the subject is a mammal. In one embodiment, the mammal is a human or non-human mammal. In one embodiment, the non-human animal is a household pet, farm animal, or zoo animal. In one embodiment, the non-human animal is a dog, cat, mouse, rat, gerbil, ferret, hamster, bird, horse, pony, donkey, mule, lama, alpaca, emu, sheep, goat, pig, cow, bull, steer, heifer, deer, tiger, cheetah, wolf, monkey, lion, bear, fox, gorilla, or kangaroo. In one embodiment, the subject is not a parasite or arthropod.
  • the present invention is a method for control of insects and/or arachnids on a subject, the method comprising contacting said insects and/or arachnids, a locus at which control is desired, said subject, or an area on or around said subject, such as clothing, blankets, collars, saddles, head collars, tags, jewellery etc., with an effective amount of a composition of the present invention.
  • the present invention is a method for control of insects and/or arachnids on a subject, the method comprising contacting said insects and/or arachnids, a locus at which control is desired, or said subject, with an effective amount of a composition of the present invention ad libitum.
  • the present invention is a method for control of insects and/or arachnids on a subject, the method comprising contacting said insects and/or arachnids, a locus at which control is desired, or said subject, with an effective amount of a composition of the present invention prior to an encounter with said insects and/or arachnids.
  • the present invention is a method for control of insects and/or arachnids on a subject, the method comprising contacting said insects and/or arachnids, a locus at which control is desired, or said subject, with an effective amount of a composition of the present invention daily, weekly, bi-weekly, monthly or annually.
  • compositions are contacted with an insect and/or arachnid, locus or subject by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention.
  • compositions of the present invention are contacted with a subject, for example, human, dog, cat, gerbil, ferret, hamster, horse, pony, donkey, mule, sheep, goat, pig, cow, bull, steer or heifer by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention.
  • a subject for example, human, dog, cat, gerbil, ferret, hamster, horse, pony, donkey, mule, sheep, goat, pig, cow, bull, steer or heifer by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention.
  • the subject is a human.
  • the subject is a household pet, such as, a dog, cat, bird, rat, mouse, ferret, gerbil or hamster.
  • the subject is a farm animal, such as, a horse, pony, donkey, mule, lama, alpaca, emu, pig, bird, cow, bull, steer, heifer, sheep, or goat.
  • a farm animal such as, a horse, pony, donkey, mule, lama, alpaca, emu, pig, bird, cow, bull, steer, heifer, sheep, or goat.
  • the present invention is a method for the modification of insect and/or arachnid behaviour at a locus causing, for example:
  • the insect, and/or arachnid to release itself from a subject after biting said subject and prior to completion of it’s blood meal and thus reducing the transmission of a pathogen; the method comprising contacting said insects and/or arachnids, a locus at which modification is desired, or a subject with an effective amount of a composition of the present invention.
  • Modification or “Modify” include causing minor, partial, median and/or major changes in, for example, insect behaviour.
  • modification of an insect and/or arachnid includes modification of their mental/physical actions as well as their biological and/or physiological responses.
  • the present invention is a method for the modification of, for example, a biochemical cement which an insect and/or arachnid, for example, a tick uses to anchor themselves to a bite site of a subject, the method comprising contacting said insects and/or arachnids, a locus at which modification is desired, or a subject with an effective amount of a composition of the present invention.
  • the methods of the present invention rapidly dislodge embedded ticks from a subject without the need for mechanical intervention.
  • the insect and/or arachnid is a flea, midge, mosquito, horse-fly, gnat, louse, tick, or mite.
  • the insect and/or arachnid is a flea, midge, mosquito, horse-fly tick, or mite.
  • the insect and/or arachnid is a tick or mite.
  • the insect and/or arachnid is a mosquito.
  • the insect and/or arachnid is a tick.
  • the present invention is a method of treating and/or preventing a disease in a subject in need thereof, wherein said disease is caused by transmission of a pathogen from a hematophagous organism to said subject, the method comprising contacting said hematophagous organism, a locus at which modification is desired or said subject, with a therapeutically effective of an emulsion or a reactive emulsion or composition of the present invention and a pharmaceutically acceptable diluent or carrier.
  • the terms “Treat”, “Treatment” and “Treating” refer to medical (therapeutic), non-medical treatments and prophylactic treatments.
  • therapeutic treatments includes the reduction, suppression or amelioration of the progression, severity and/or duration of a condition, or the amelioration of one or more symptoms (including, one or more discernible symptoms) of a condition, resulting from the administration of one or more compositions of the present invention.
  • the therapeutic treatment includes the amelioration of at least one measurable physical parameter of a condition.
  • the therapeutic treatment includes the inhibition of the progression of a condition, either physically by, e.g., stabilization of a discernible symptom, physiologically by, e.g., stabilization of a physical parameter, or both.
  • Non-medical treatments include, for example, treating an infestation by reducing the number or completely eliminating, for example, an arthropod from a locus.
  • the terms “prophylaxis” or “prophylactic use” and “prophylactic treatment” as used herein, refer to preventing rather than treating or curing a condition or infestation.
  • the terms “Prevent”, “Prevention” and “Preventing” refer to the reduction in the risk of acquiring or developing a given condition or infestation, or the reduction or inhibition of the recurrence or said condition or infestation.
  • condition includes disease, illnesses, sickness, infection, and/or biological (including immunological and physiological) response.
  • the subject is a human or nonhuman animal. In another embodiment the subject is a mammal. In one embodiment, the mammal is a human or non-human mammal. In one embodiment, the mammal is a human. In one embodiment of the present invention, the non-human mammal is a household pet, farm animal or zoo animal.
  • the non-human animal is a dog, cat, mouse, rat, gerbil, ferret, hamster, bird, horse, pony, donkey, mule, lama, alpaca, emu, sheep, goat, pig, cow, bull, steer, heifer, deer, tiger, cheetah, wolf, monkey, lion, bear, fox, gorilla, or kangaroo.
  • the subject is not a parasite, insect, and/or arachnid. In one embodiment, the subject is not a parasite or arthropod.
  • the present invention is a method of treating and/or preventing a disease in a subject in need thereof, wherein said disease is caused by a pathogen transmitted to said subject by an insect, arachnid, and/or parasite the method comprising contacting said parasites, insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention.
  • the invention is a method of treating and/or preventing a disease in a subject in need thereof, wherein said disease is caused by a pathogen transmitted to said subject by an insect, arachnid, and/or parasite comprising contacting said parasites, insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject with a therapeutically effective amount topical composition of the present invention and a pharmaceutically acceptable diluent or carrier.
  • the invention is a method of treating and/or preventing a subdermal, intradermal or subcutaneous disease in a subject in need thereof, wherein said disease is caused by a pathogen transmitted to said subject by an insect, arachnid, and/or parasite comprising contacting said parasites, insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject with a therapeutically effective amount composition of the present invention and a pharmaceutically acceptable diluent or carrier.
  • the disease is Anaplasmosis, Human Granulocytic Anaplasmosis, Babesiosis, Borrelia mayonii infection, Borrelia miyamotoi infection, Bourbon virus infection, Colorado tick fever, Alkhurma Haemorrhagic Fever, Ehrlichiosis, Heartland virus, Lyme disease , Powassan disease, Rickettsia parkeri rickettsiosis, Rocky Mountain spotted fever (RMSF), STARI (Southern tick-associated rash illness), Tickborne relapsing fever (TBRF), Tularemia, Rickettsiosis, Tick borne encephalitis, Akabane virus, Schmallenberg, Blue-tongue, Equine infectious anaemia, Anthrax, Trypanosomes (trypanosoma/Chagas), Malaria, Dengue, Yellow fever, Zika virus, Chikungunya, Human Lymphatic Filariasis, Black death, Plague, Bu
  • the parasite, insect and/or arachnid is flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, ant, spider, tick, mite, scorpion, pseudoscorpion, harvestmen, camel spider, whip spider, or vinegarroon.
  • the insect is a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, or ant.
  • the Aracnhid is a spider, tick, mite, scorpion, pseudoscorpions, harvestmen or vinegaroons.
  • the flea is Tunga penetrans, chigoe, chigo, chigoe flea, chigo flea, jigger, nigua, sand flea, or burrowing flea.
  • the mite is Sarcoptes scabiei var. hominis, Trombiculidae; harvest mite, berry bug, bush-mite, red bus or scrub-itch mite.
  • the parasite is Loa Loa.
  • the invention is a method of treating and/or preventing a disease in a subject in need thereof, wherein said disease is caused by a pathogen transmitted by an hematophagous organism to said subject , the method comprising contacting said organism, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention.
  • the disease is Anaplasmosis, Human Granulocytic Anaplasmosis, Babesiosis, Borrelia mayonii infection, Borrelia miyamotoi infection, Bourbon virus infection, Colorado tick fever, Alkhurma Haemorrhagic Fever, Ehrlichiosis, Heartland virus, Lyme disease , Powassan disease, Rickettsia parkeri rickettsiosis, Rocky Mountain spotted fever (RMSF), STARI (Southern tick-associated rash illness), Tickborne relapsing fever (TBRF), Tularemia, Rickettsiosis, Tick borne encephalitis, Akabane virus, Schmallenberg, Blue-tongue, Equine infectious anaemia, Anthrax, Trypanosomes (trypanosoma/Chagas), Malaria, Dengue, Yellow fever, Zika virus, Chikungunya, Human Lymphatic Filariasis, Black death, Plague, Bu
  • the parasite, insect and/or arachnid is flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, ant, spider, tick, mite, scorpion, pseudoscorpion, harvestmen, camel spider, whip spider, or vinegarroon.
  • the insect is a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, or ant.
  • the Aracnhid is a spider, tick, mite, scorpion, pseudoscorpions, harvestmen or vinegaroons.
  • the flea is Tunga penetrans, chigoe, chigo, chigoe flea, chigo flea, jigger, nigua, sand flea, or burrowing flea.
  • the mite is Sarcoptes scabiei var. hominis, Trombiculidae; harvest mite, berry bug, bush-mite, red bus or scrub-itch mite.
  • the parasite is Loa Loa.
  • compositions treat and/or prevent a subdermal, intradermal or subcutaneous disease in a subject.
  • compositions are applied topically to a subject and treat and/or prevent a subdermal, intradermal or subcutaneous disease in said subject.
  • the present invention is a method of treating and/or preventing a disease in a subject in need thereof, wherein said disease is caused by transmission of a pathogen from a hematophagous organism to said subject, the method comprising contacting said insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention prior to an encounter with said insects and/or arachnids.
  • the present invention is a method of treating and/or preventing a disease in a subject in need thereof, wherein said disease is caused by transmission of a pathogen from a hematophagous organism to said subject, the method comprising contacting said insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention daily, weekly, bi-weekly, monthly, or annually.
  • compositions are contacted with an insect and/or arachnid, locus or subject by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention.
  • compositions of the present invention are contacted with a subject, for example, human, dog, horse, cat, bird, rat, mouse, ferret, gerbil, hamster, pig, cow, bull, steer and heifer, sheep, or goat by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention.
  • a subject for example, human, dog, horse, cat, bird, rat, mouse, ferret, gerbil, hamster, pig, cow, bull, steer and heifer, sheep, or goat by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention.
  • the invention is a method for controlling a parasite, insect and/or arachnid and treating and/or preventing a disease in a subject transmitted to said subject by said parasite, insect and/or arachnid.
  • the subject is a human.
  • the subject is a household pet, such as, a dog, horse, cat, bird, rat, mouse, ferret, gerbil or hamster.
  • the subject is a farm animal, such as, a pig, cow, bull, steer and heifer, sheep, or goat.
  • the parasite, insect and/or arachnid is flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, ant, spider, tick, mite, scorpion, pseudoscorpion, harvestmen, camel spider, whip spider, or vinegarroon.
  • the insect is a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, or ant.
  • the Aracnhid is a spider, tick, mite, scorpion, pseudoscorpions, harvestmen or vinegaroons.
  • the flea is Tunga penetrans, chigoe, chigo, chigoe flea, chigo flea, jigger, nigua, sand flea, or burrowing flea.
  • the mite is Sarcoptes scabiei var. hominis, Trombiculidae; harvest mite, berry bug, bush-mite, red bus or scrub-itch mite.
  • the parasite is Loa Loa.
  • the disease is Anaplasmosis, Human Granulocytic Anaplasmosis, Babesiosis, Borrelia mayonii infection, Borrelia miyamotoi infection, Bourbon virus infection, Colorado tick fever, Alkhurma Haemorrhagic Fever, Ehrlichiosis, Heartland virus, Lyme disease , Powassan disease, Rickettsia parkeri rickettsiosis, Rocky Mountain spotted fever (RMSF), STARI (Southern tick-associated rash illness), Tickbome relapsing fever (TBRF), Tularemia, Rickettsiosis, Tick borne encephalitis, Akabane virus, Schmallenberg, Blue-tongue, Equine infectious anaemia, Anthrax, Trypanosomes (trypanosoma/Chagas), Malaria, Dengue, Yellow fever, Zika virus, Chikungunya, Human Lymphatic Filarias
  • the disease is Lyme disease (Borreliosis), Tick Borne Encephalitis, Alkhurma Haemorrhagic Fever, Colorado Tick Fever, Babesiosis, Crimean-Congo Haemorrhagic Fever, Human Granulocytic Anaplasmosis, Ricketsiosis and Tick Borne Relapsing Fever.
  • the disease is Zika virus.
  • the compounds described herein can be formulated into pharmaceutical compositions that further comprise a pharmaceutically acceptable carrier, diluent, adjuvant or vehicle.
  • the present invention relates to a pharmaceutical composition comprising a composition and/or emulsion of the invention described herein, and a pharmaceutically acceptable carrier, diluent, adjuvant or vehicle.
  • the present invention is a pharmaceutical composition comprising an effective amount of an emulsion or a reactive emulsion of the present invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, diluent, adjuvant or vehicle.
  • Pharmaceutically acceptable carriers include, for example, pharmaceutical diluents, excipients or carriers suitably selected with respect to the intended form of administration, and consistent with conventional pharmaceutical practices.
  • a pharmaceutically acceptable carrier may contain inert ingredients which do not unduly inhibit the biological activity of the compounds.
  • the pharmaceutically acceptable carriers should be biocompatible, e.g., non-toxic, non-inflammatory, non-immunogenic or devoid of other undesired reactions or side-effects upon the administration to a subject. Standard pharmaceutical formulation techniques can be employed.
  • the pharmaceutically acceptable carrier, adjuvant, or vehicle includes any and all solvents, diluents, or other liquid vehicle, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, lubricants and the like, as suited to the particular dosage form desired.
  • Remington s Pharmaceutical Sciences, Sixteenth Edition, E. W. Martin (Mack Publishing Co., Easton, Pa., 1980) discloses various carriers used in formulating pharmaceutically acceptable compositions and known techniques for the preparation thereof.
  • any conventional carrier medium is incompatible with the compounds described herein, such as by producing any undesirable biological effect or otherwise interacting in a deleterious manner with any other component(s) of the pharmaceutically acceptable composition, its use is contemplated to be within the scope of this invention.
  • an “Effective amount” includes a “Therapeutically effective amount” and a “Prophylactically effective amount”.
  • the term “Therapeutically effective amount” refers to an amount effective in treating and/or ameliorating a condition or infestation.
  • the term “Prophylactically effective amount” refers to an amount effective in preventing and/or substantially lessening the condition or infestation. Specific examples of effective amounts are described herein.
  • compositions of the present invention comprise between 2% by weight and 60% by weight of an emulsion or a reactive emulsion of the present invention containing no less than 1% by weight and no more than 25% by weight of oil phase wherein the oil phase is no less than 40% by weight of free fatty acid and no more than 60% by weight triglyceride.
  • compositions of the present invention are applied in an amount sufficient to cover the insect or the locus which is the intended target of the insect or the area of a subject affected by hematophagous or parasitic insects.
  • the insect and/or arachnid is a flea, midge, mosquito, horse-fly, gnat, louse, tick, or mite.
  • the insect and/or arachnid is a flea, midge, mosquito, horse-fly tick, or mite.
  • the insect and/or arachnid is a tick or mite.
  • the insect and/or arachnid is a mosquito.
  • the insect and/or arachnid is a tick.
  • present invention is a method for suppression, treatment and/or prevention of a physiological and/or immunological response of a subject in need thereof to a bite and/or a sting from an insect and/or arachnid, the method comprising contacting said insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of composition of the present invention and a pharmaceutically acceptable diluent or carrier.
  • present invention is a method for suppression, treatment and/or prevention of a physiological and/or immunological response of a subject in need thereof to a bite from a hematophagous organism, the method comprising contacting said hematophagous organism, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention.
  • the subject is a human or non-human animal. In another embodiment the subject is a mammal. In one embodiment, the mammal is a human or non-human mammal. In one embodiment, the mammal is a human. In one embodiment of the present invention, the non-human mammal is a household pet, farm animal or zoo animal.
  • the non-human animal is a dog, cat, mouse, rat, gerbil, ferret, hamster, bird, horse, pony, donkey, mule, lama, alpaca, emu, sheep, goat, pig, cow, bull, steer, heifer, deer, tiger, cheetah, wolf, monkey, lion, bear, fox, gorilla, or kangaroo.
  • the subject is not a parasite, insect, and/or arachnid.
  • compositions of the present invention suppress, treat and/or prevent a physiological and/or immunological response of a subject by modification of the biochemistry of tick saliva and/or other secretion.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to an insect and/or arachnid bite and/or sting, wherein the physiological and/or immunological response is, for example, inflammation; itchiness; erythema; hives; redness; pain; vasoconstriction; platelet aggregation; degranulation of mast cells; release of dendritic cells; activation of fibroblasts, fibrinogen, bradykinins, histamines, or chemoattractant (chemokines or leukotrienes); transport of neutrophils or monocytes; or generating antigen specific antibodies or T lymphocytes.
  • physiological and/or immunological response is, for example, inflammation; itchiness; erythema; hives; redness; pain; vasoconstriction; platelet aggregation; degranulation of mast cells; release of dendritic cells; activation of fibroblasts, fibrinogen, brady
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a bite or sting from an insect and/or arachnid, such as, a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, ant, spider, tick, mite, scorpion, pseudoscorpion, harvestmen, camel spider, whip spider, or vinegarroon.
  • an insect and/or arachnid such as, a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, assassin bug, gnat, louse, sawfly, ant, spider, tick, mite, scorpion, pseudoscorpion, harvestmen, camel spider, whip spider, or vinegarroon.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a bite from an insect and/or arachnid, such as, a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, gnat, louse, spider, tick, or mite.
  • a subject such as, a flea, midge, mosquito, horse-fly, tsetse fly, sandfly, blackfly, bedbug, gnat, louse, spider, tick, or mite.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a bite from an insect and/or arachnid, such as, a flea, midge, mosquito, horse-fly, gnat, louse, tick, or mite.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a bite from an insect, such as, a flea, midge, mosquito, horse-fly, gnat, or louse.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a bite from a mosquito.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a bite from an arachnid, such as, a tick or mite.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a bite from a tick.
  • compositions of the present invention suppress, treat and/or prevent a subject’s physiological and/or immunological response to a sting from an insect and/or arachnid, such as, spider, scorpion, or ant.
  • the present invention is a method of suppressing, treating and/or preventing a physiological and/or immunological response in a subject in need thereof, wherein said disease is caused by transmission of a pathogen from a hematophagous organism to said subject, the method comprising contacting said insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention ad libitum.
  • the present invention is a method of suppressing, treating and/or preventing a physiological and/or immunological response in a subject in need thereof, wherein said physiological and/or immunological response is caused by a bite or sting from a hematophagous organism to said subject, the method comprising contacting said insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention prior to an encounter with said insects and/or arachnids.
  • the present invention is a method of suppressing, treating and/or preventing a physiological and/or immunological response in a subject in need thereof, wherein said physiological and/or immunological response is caused by a bite or sting from a hematophagous organism to said subject, the method comprising contacting said insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention once, twice or more.
  • the present invention is a method of suppressing, treating and/or preventing a physiological and/or immunological response in a subject in need thereof, wherein said physiological and/or immunological response is caused by a bite or sting from a hematophagous organism to said subject, the method comprising contacting said insects and/or arachnids, a locus at which treatment and/or prevention is desired, or said subject, with a therapeutically effective amount of a composition of the present invention daily, weekly, biweekly, monthly, or annually.
  • compositions are contacted with an insect and/or arachnid, locus or subject by spraying a spray or aerosol or application of a liquid, gel, powder, paste, ointment, cream, surface coating, soap, dry residue, lotion or wipe comprising the compositions of the present invention.
  • compositions of the present invention prevents and/or treats a disease at, for example, a bite site on a subject by, for example: o modifying the behaviour of an arthropod, such as:
  • ⁇ modifying biological chemistry of an arthropod for example:
  • the present invention is a method for the manufacture of the emulsions of the present invention as described herein.
  • a manufacturing method for a free fatty acid oil in de-lipidised lecithin amphipath is described in WO 2011/ 061237. Similar methods may be employed to construct emulsions of the present invention.
  • a secondary high pressure homogenisation step is employed in addition to the methods of WO 2011/061237, to reduce mean particle (emulsion droplet) size to less than 1 micron, preferably in the region of between 0.8 and 0.6 micron, and preferably still less than 0.5 micron.
  • an oil phase is constructed by blending one or more free fatty acids with or without a neutral tri-glyceride added and dispersing this in a pre-hydrated suspension of amphipath using a laboratory homogeniser such as an Ultra Turax Model T-25 (IKA Works, NC 28405, USA), fitted with S25N-25G dispersing tool running at 6,000 RPM. Emulsification methods are well known to those skilled in the art.
  • the emulsions of the present invention have a mean particle (droplet) size of between 1 and 0.5 microns. In one embodiment, the emulsions of the present invention have a mean particle (droplet) size of between 1 and 0.5 microns as measured using a Malvern Mastersizer 3000 with Malvern Hydro EV Sampler running on software version 3.7.
  • the emulsions of the present invention form the Ultra Turax as described above will have a mean particle (droplet) size of between 1 and 0.5 microns as measured using a Malvern Mastersizer 3000 with Malvern Hydro EV Sampler running on software version 3.7.
  • emulsions of the present invention have a mean particle (droplet) size greater than 1 micron. In another embodiment, the emulsions of the present invention have a mean particle (droplet) size of less than 1 micron.
  • Emulsions with mean droplet size greater than 1 micron will have anti -arthropod, antiarthropod borne infection, anti-parasitic, insecticidal and arachnidicidal activities.
  • emulsions of the present invention which undergo a secondary homogenisation step to reduce the mean droplet size to less than 1 micron have unexpectedly greatly enhanced efficacy and stability with comparison to the prior art emulsions.
  • a secondary homogenisation step is performed using a GEA Niro Soave Panda Plus 200N high pressure homogeniser (or similar) running at 1000 bar pressure and operated according to the manufacturer’s instructions.
  • one or more homogenisation steps are used to achieve adequate reduction of droplet size.
  • the free fatty acid used in the oil phase is selected from Caproic, Caprylic, Capric, Undecylenic, Lauric, Myristic, Palmitic, Stearic, Oleic, Palmitoleic, Linoleic, linolenic and arachidonic acid, preferably Caproic, Caprylic, Capric undecylenic and Oleic, and more preferably still Caprylic and Capric acid.
  • Caproic, Caprylic, Capric undecylenic and Oleic are available from Merck, Germany.
  • the free fatty acid oils are diluted with a neutral triglyceride oil.
  • Suitable oils include those of vegetable origin such as olive, peanut, Canola and coconut.
  • Synthetic triglycerides may also be used and these are preferable for quality reasons. Synthetic triglycerides include those commercially available from Cremer Oleo GmBH, Hamburg Germany marketed under the Miglyol range.
  • Mglyol 812N is a mixed Capric Caprylic Triglyceride and Miglyo 818N is a Caprylic tri-glyceride. Miglyol 812N is preferred.
  • a neutral triglyceide is used to dilute the free fatty acid oil phase.
  • the triglyceride constitutes between 5% and 60% by weight of total oil (oil phase), preferably the neutral triglyceride should be between 5% and 30% by weight more preferably between 10% and 20% of the total oil (oil phase).
  • the total oil (oil phase) is from 2% to 40% of the emulsion of the present invention by weight, preferably 5% to 35% and more preferably 10% to 20%.
  • the emulsions further comprise a surfactant.
  • the surfactant is used to improve dispersion of the oil in the hydrated amphipath.
  • Suitable surfactants may be selected from Anionic, cationic, non-ionic or amphoteric surfactants.
  • Anionic surfactants include salts of free fatty acids such as sodium oleate.
  • Cationic surfactants include lecithin and its constituent phosphatides. Examples of amphoteric surfactants are betaine and sulpho-betaine.
  • Non-ionic surfactants include a series of chemical polymers conventionally known as Tween: Tween 20 is polyoxyethylene sorbitan ester; Tween 40 is polyoxyethylene sorbitan monopalmitate while Tween 80 is polyoxyethylene sorbitan mono-oleate. While any surfactant may be used in the construction of the emulsions of this invention lecithin and one of the Tweens is preferred, preferably lecithin and Tween 80.
  • the amphipath is an emulsification agent which is amphipathic having opposing aspects which are hydrophilic and lipophilic. Suitable amphipaths may be selected from Lanolin, Ceramide, cholesterol or lecithin. As well as being a cationic surfactant, lecithin is also an amphipath. Lecithin is the preferred amphipath. Lecithin exists naturally as a combination of five separate phosphatides: phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl glycerol and phosphatidic acid. The ratio of phosphatides influences the emulsification properties and may be manipulated to modify the characteristics of the emulsions of this invention. Increased concentration of phosphatidyl choline and phosphatidyl ethanolamine are preferred and more preferable lecithins with at least 60% phosphatidyl choline and no more that 5% phosphatidic acid are preferred.
  • an amphipath is de-lipidised in a manner which leaves its constituent lipophilic sites free to associate with the oil phase.
  • de-lipidisation is achieved by repetitive suspension in a solvent such as acetone, precipitation and drying of the precipitate by solvent evaporation.
  • a solvent such as acetone
  • precipitation and drying of the precipitate by solvent evaporation are available commercially as extract of egg or soy.
  • the amphipath used in the methods of the present invention is soy lecithin is which has been de- lipidised to less than 5% by weight of extraneous lipid or oil.
  • a chemically modified lecithin is used to improve electro-static repulsion between emulsified oil droplets thereby improving emulsion stability.
  • Suitable modified lecithin include di-palmitoyl phosphatidyl choline (DPPC) and di-palmitoyl phosphatidyl glycerol (DPPG) both available from Lipoid AG, Steinhausen, Switzerland.
  • chemically modified lecithin comprises no more than 60% by weight of de-lipidised lecithin, preferably between 10% and 50% and more preferably between 20% and 40% by weight of lecithin.
  • the emulsions of the present invention further comprise a thickener such as glycerol, Xanthan gum, Guar gum or gum Acacia.
  • a thickener such as glycerol, Xanthan gum, Guar gum or gum Acacia.
  • long term stability of the emulsions is improved by the use of a thickener such as glycerol, Xanthan gum, Guar gum or gum Acacia.
  • the emulsions further comprise synthetic polymers.
  • synthetic polymers improve the rheology and stability of the emulsions of the present invention. Suitable synthetic polymers include cellulose derivatives such as carboxy methyl cellulose, and the Carbopols from Noveon Polymers, Cleveland, Ohio, USA.
  • the emulsions further comprise acidity regulators and buffers. Further stability and efficacy may be achieved through the use of acidity regulators and buffers to maintain a desired pH during application.
  • Suitable buffers are organic acids and salts thereof including sodium and potassium phosphate, lactate, citrate and benzoate.
  • the product of Table 1 is a 20% oil emulsion which is incorporated in finished formulations at dose loadings of between 1 and 20%, preferably between 2% and 10% and more preferably between 4% and 8%.
  • a lower total oil phase may be used as exemplified in Table 2 where 10% oil with higher neutral tri-glyceride (Miglyol) is demonstrated using Lipoid DPPG to enhance emulsion stability.
  • the product of Table 2 is a 10% oil emulsion which is incorporated in finished formulations I dose loadings of between 1% and 20%, preferably 2% to 10% and more preferably between 4% and 8% by weight.
  • emulsions can be constructed with total oil (oil phase) ranging from 3% to 30% by weight, preferable 5 to 25% and more preferable 10% to 20%.
  • the concentration of the oil phase requires adjustment of the concentration of de-lipidised lecithin or other amphipath to maintain stability of the emulsion.
  • the weight ratio of amphipath to oil is between 0.1 to 1.0 or between 0.5 to 1 or 1 to 1 or 1 to 0.5.
  • the weight ratio of neutral oil to free fatty acid in the oil phase may be varied between 0% and 60% triglyceride to 100% to 40% free fatty acid in order to modulate the potency and rate of release of amphipathic emulsification agent.
  • Cockroaches include the large American cockroach, Periplanetta americans. the smaller Oriental cockroach, Blata orienlaHs. and the smallest German cockroach Blattella germanica.
  • the mid-sized Oriental cockroach was collected from a disused grain store prior to decontamination by a pest control company. Cockroaches are easily cared for in a laboratory setting and are frequently used for education and scientific research purposes. A suitable treatise on the laboratory management of cockroaches is available from Chapman and Hall publishers: W. J. Bell 1981; The laboratory management of cockroach. ISBN 978-0-412- 23990-8
  • Fleas (Siphonaptera), of which there are over 2,500 known species the most common of which are the domestic dog and cat flea, Cteonocephalides canis and C. felis
  • Cat fleas were collected by grooming cats in a pet rescue centre and transported to a laboratory for testing within 1 hour of collection.
  • Ticks (Ixodida) of which there are some 700 species of hard bodies tick and 200 soft bodies.
  • the most notable species associated with arthropod borne infection include the sheep tick Ixodes Ricinus. the black legged deer tick Ixodes scapularis and the lone star tick Amblyomma Americanum.
  • Ixodes Ricinus was collected during summer months from a forest area known to hold a heavy density of red deer and known to be infected with Ixodes. Ticks are easily collected by dragging a white sheet over ground where long grass is growing. Ticks will cling on to the underside of the sheet and can be collected from there using a fine brush to transfer them to a plastic container with lid. Freshly collected ticks were transported to a laboratory for testing within 1 hour of collection.
  • Aedes aegypti were obtained from an established colony and maintained in a laboratory using established methods described in detail by S. W. Masters et.al. Rearing Aedes aegypti Mosquitoes in a Laboratory Setting. Lab Animal Sci Prof. 2020 Nov’; 55(6): 42-45.
  • Midge (Diptera, Ceratopogonidae), there are many different species some bite and some do not. Of the biting midge species Culicoideslegictatus is notorious and responsible for transmission of many animal infections.
  • Head lice were collected by a school hygiene specialist from school children aged 6 years to 10 years by combing hair using a fine toothed comb.
  • Example 1 Anti-arthropod formulation effect on cockroach (Blata orientalis).
  • the emulsion concentrate from Table 1 was diluted to 5% by weight in sterile distilled water: 5 grams of emulsion concentrate was added to 95 grams of water and stirred to disperse fully. It should be noted that this dilution contains 0.8% caprylic acid, 0.2% Miglyol 812N (neutral triglyeride), 0.01% Tween 80, 0.15% de-lipidised lecithin, and 0.0075% xanthan gum. The diluted emulsion was loaded into a HDPE spray bottle.
  • a ’control’ or blank formulation was sterile distilled water in a similar HDPE spray bottle.
  • cockroaches were selected from a batch of 40 collected as described above.
  • insects were evaluated after one hour and scored according to observable movement: 1) immovable, was considered dead or paralysed; 2) moribund, showing some signs of movement; 3) alive, walking and moving freely.
  • test formulation Of the ten insects that received test formulation seven were dead and three were moribund after one hour.
  • the test was repeated three times with no recovery of moribund insects after 10 hours and was therefore considered to be 100% effective after 1 hour.
  • Table 2 formulation is 10% oil (half that of Table 1) the formulation was diluted to 10% in sterile distilled water to achieve an equivalent concentration.
  • a minimum dose volume of 0.2 grams was determined but it should be noted that these results are an estimate of dose volume only, not dose concentration.
  • the actual dose delivered in 0.2 grams of formulation was 1.6mg caprylic acid, 0.4. mg Miglyol, 0.02mg Tween 80, 0.3 mg de-lipidised lecithin and 0.015 mg xanthan gum.
  • Example 2 Evaluation of mode of action of test formulation.
  • the large American cockroach Periplanata americana were used to evaluate mode of action because of their size which greatly facilitates dissection and post mortem evaluation.
  • cockroaches have typical insect anatomy, in particular their breathing apparatus consists of a series of small openings called spiracles located laterally along both sides of their thorax which led to trachea and tracheole disseminated through their body. Breathing relies on a pumping mechanism activated by abdominal muscles. Additionally cockroaches have a mouth, oesophagus, alimentary canal and anal orifice
  • the emulsion concentrate from Table 1 was diluted to 5% by weight in sterile distilled water containing 1% ponceau red dye.
  • a control was used consisting of water only with 1% ponceau red dye.
  • the dyed formulation Upon dissection the dyed formulation was observed to have penetrated the spiracles and travelled throughout the trachea and tracheole. The dyed formulation was also evident in the oesophagus and lower alimentary tract where it had penetrated through the anal orifice. The dyed formulation was not detected in the internal tissue or the fat bodies (energy stores).
  • the mode of action is considered to be a physical rather than chemical intervention, primarily suffocation due to gross blockade of the breathing apparatus.
  • One of the unique characteristics of the emulsions of the present invention is that they exert dramatic wetting of hydrophobic surfaces due to phase inversion by the amphipath.
  • the cuticle of most insects is a waxy surface which is extremely hydrophobic (lipophilic) and which repels water preventing ingress at the spiracles. Provided its lipophilic sites are free to associate, delivery of an amphipath to the insect cuticle and spiracles will result in phase inversion of the surface from lipophilic to hydrophilic permitting immediate ingress of aqueous material to the trachea and also the mouth, oesophagus and anal orifice.
  • Example 3 Efficacy against Head Lice Pediculus humanis captis.
  • the emulsion concentrate from Table 1 was diluted to 5% by dispersing 5 grams in 95 grams of sterile distilled water. This is similar to the test items used in Example 1 and contains the same concentration and ratio of ingredients.
  • Head lice were collected as described above. Test insects were confirmed to be alive before testing.
  • a 10 minute exposure of the 5% aqueous dispersion of test formulation achieved greater than 60% mortality of head lice under the test conditions. Greater efficacy may be anticipated In Vivo use or with higher concentrations over longer exposure times and with optional excipients designed to enhance physical contact with the insects.
  • test formulation was a 5% dispersion of the emulsion concentrate from Table 1 in sterile distilled water containing 1% Ponceau Red dye.
  • the control was ponceau red dye in water only.
  • Test insects were first confirmed to be alive and then placed on cotton gauze sections and immersed in test or control for one hour after which they were rinsed with clean water, dried on blotting paper and examined under a microscope.
  • the mode of action was deemed to be due to physical damage caused by ingress of the formulation through natural orifices.
  • Example 2 a prototype gel was used incorporating the emulsion from Table 1 with added glycerol and Xanthan gum to achieve a slightly sticky formulation that will stay in place when applied to insects that may be residing or embedded in skin, hair or fur.
  • Sodium citrate was also used here as a buffer. The combination of excipients was shown to improve efficacy by controlling pH and increasing contact with the insect’s surface.
  • the formulation is sufficiently sticky to adhere to skin, hair and fur it is pourable and very easy to rinse off with water.
  • Ticks were collected from the field in the manner described above and used in test within one hour of collection.
  • Ticks were assembled in small (35mm) petri dishes in lots of 5 individuals and all confirmed to be alive before exposure to test items.
  • the gel blank had a deleterious effect on one of the five test insects over two hours but four were unaffected. Two hours later and overnight, the affected insect was dead but all of the other four started moving when poked with a tweezers.
  • a 5% aqueous dispersion of the emulsion in Table 1 has a potent effect on ticks (Ixodes Ricirms). Potency is amplified slightly using gel excipients to improve adherence to the insect and an organic acid buffer to maintain acidity. The buffered gel has very little effect without the emulsion.
  • Example 6 In Vivo assessment against tick (Ixodes Ricinus) The protective effect of the gel formulation in Example 5 was demonstrated and also the utility of the same formulation in dislodging embedded tick from a human subject.
  • a one inch wide ring of the gel was applied to the upper leg (thigh) of a human subject, the “treated area”, leaving a three inch diameter inner circle with no gel.
  • Ticks move relatively quickly and the test insect made its way onto the treated area within a minute of placement. As soon as the insect entered the treated area it started showing signs of distress - short jerking movements with front legs waving erratically. Location movement stopped after about 2 minutes and the tick turned itself upside down after 4 minutes. All movement ceased after 8 minutes and the insect was removed to a petri-dish where it was observed for a further four hours and showed no signs of recovery during that time.
  • ticks were then placed on clean untreated human subject’s skin and retained in place by taping an inverted 35mm petri-dish over the insects.
  • the insects wandered inside the isolated area for about 10 minutes before one bit and quickly became embedded in the subject’s skin.
  • the petri-dish was removed along with the other two ticks and the embedded tick was left in place for two hours to become established.
  • an aliquot of about 0.5 ml of the 5% emulsion gel (Example 5, Table 5) was applied to the tick, and spread about 1 cm diameter around the bite site and left for 10 minutes.
  • gentle rotation of a finger caused the tick to come away from the bite site.
  • the tick was placed in a plastic container and observed for a further four hours during which time no movement was observed.
  • the tick was anatomically intact: the scutum and mouth parts were still attached.
  • Culicoides is a genus of biting midge in which there are over 1,000 species and much debate about taxonomic validity: abnormalctatus, recsis and scoticus are examples commonly referenced. Regardless of classification all are potential vectors of viral disease in animals and all are notorious for the irritation they cause to humans especially outdoors during late evenings.
  • Culicoides sp can be collected by trapping them on a muslin screen over an electric light bulb just before dark on summer evenings. Because of the small size it is difficult to determine if they are alive or dead and consequently In Vitro evaluation of efficacy was abandoned.
  • Example 8 Efficacy against fleas (Cteonocephalides felis and C. canis)
  • Cat fleas were collected from a pet rescue centre as described above.
  • a water dispersion of 5% emulsion from Table 1 was constructed by adding 5 grams of emulsion concentrate to 95 grams of sterile distilled water and mixing thoroughly. The emulsion diluent was placed in a hand held HDPE spray bottle for application. A similar spray bottle containing sterile distilled water only was used as a control.
  • DPPG Lipoid di-Palmitoyl-phosphatidylglycerol
  • Example 1 In use as aqueous dispersions (Examples 1, 2, 3 , 4 and 8) the emulsions were diluted to achieve similar concentration of total oil (oil phase), but again, the oil ratio differed.
  • examples 5, 6 and 7 the emulsions was delivered in the form of a gel containing 10% glycerol and 1% Xanthan Gum in 50mM sodium citrate buffer.
  • Example 5 the gel blank was shown to have no effect on the test insect, and so it is reasonable to suggest that none of the gel constituents contributed to efficacy.
  • aqueous dispersion of de-lipidised lecithin and DPPG is prepared by blending the component with water at the desired concentration and allowing at least one hour to fully hydrate. The dispersion should be shaken before use as there is a tendency to settle out.
  • Caprylic acid or Miglyol are water soluble
  • dispersions are achieved with the aid of a laboratory homogeniser (Ultra Turax as described in the methods), however these dispersions will co- acervate and settle out within minutes of being formed and so they were used in this example immediately after they were prepared.
  • the cockroach Blata orientalis was used as described in Example 1 part 3 because of its size, ease of application and predictable response to the formulation.
  • Pairs of insects were treated by applying 0.3 grams (ml) of test items from Table 9 above directly onto their backs following which individual insects were placed in separate plastic containers and observed over a period of one hour and overnight.
  • a 5% aqueous dispersion of the emulsion from Table 1 and sterile distilled water were used as controls.
  • Both Aphids and White Fly are sap-sucking parasites on plants causing significant leaf damage and in addition both are common vectors of plant virus disease. Infestation of glasshouse plants is easily detected by visual inspection of the underside of leaves and the crook between leaf and stem for aphid. Unlike Aphids, Whitefly do fly and tend to disperse in clouds when a plant is disturbed . A particularly heavily infested domestic glasshouse (both whitefly and Aphid) growing tomatoes and strawberries) was selected for testing the formulation.
  • a water dispersion of 5% emulsion from Table 1 was constructed by adding 5 grams of emulsion concentrate to 95 grams of sterile distilled water and mixing thoroughly. The emulsion diluent was placed in a hand held HDPE spray bottle for application .A similar spray bottle containing sterile distilled water only was used as a control.
  • Ants will devastate soft fruit such as strawberries and frequently establish a commensal relationship with Aphids. Ants are known to ‘farm’ aphids by moving them into colonies in order to feed off the honeydew secretions typically seen where infestation is heavy.
  • Ants will establish nests in soft dry soil in glasshouses. Frequently the entrance hole is adjacent to a concrete pathway to give physical support for the subterranean structure . Digging out individual ants nests is pointless because they will spread and establish new nests.
  • a dispersion of the emulsion of Table 1 was used at 10% concentration by adding 10 grams of emulsion concentrate to 90 grams of sterile distilled was and dispensing this from a spray bottle similar to those used to treat aphid infestation.
  • the location of ants nests was determined by visual observation of where individuals were travelling to. Once located the entrance hole and the surrounding ground was saturated with spray of 10% emulsion. Individual ants in the locality were also sprayed. The procedure was repeated twice daily for three days after which no ants were observed entering or leaving the nest entrance. It is thought that ants transiting the sprayed area were affected by the emulsion and died in the nest.
  • the emulsion from Table 1 (reactive emulsion) was adjusted by removing the free fatty acid (caprylic) and replacing it on a weight by weight basis with neutral triglyceride (Miglyol 812N), Table 11, to create a non-reactive emulsion. After high pressure homogenisation the concentrate was diluted to 5% by weight with water. The emulsion of Table 1 diluted to 5% in water was used as a positive control and water was used as a blank.
  • the Oriental Cockroach Blata Orientalis was used to evaluate the efficacy of the non-reactive emulsion and the experimental design was the same as in Example 1. Individual insects were lifted with tweezers and sprayed with either non-reactive test formulation, positive control or water blank, ten insects in each case, and evaluated after 1 hour and 10 hours.
  • Example 12 Reactive Emulsion used as a delivery system for conventional oil soluble insecticides.
  • Permethrin is a pyrethroid derivative, it is routinely used as a treatment for head lice and scabies in humans for which it is approved by FDA as a 1% solution. Permethrin is effective against adult lice but not their eggs. Although considered safe for skin contact it can have serious adverse effect particularly if accidentally swallowed or because of its low vapour pressure it can be inadvertently inhaled.
  • Permethrin Although basically oil soluble, Permethrin is sparingly soluble in water and a water control was prepared by dissolving 0.1% Permethrin in water at 25°C
  • a Reactive Emulsion control was prepared using the formulation in Table 13 by replacing Permethrin with Miglyol at 15% and free fatty acid at 5%.
  • Example 1 Water was used as a blank.
  • the Oriental Cockroach Blata Orientalis was used to evaluate the efficacy of the non-reactive emulsion and the experimental design was the same as in Example 1. Individual insects were lifted with tweezers and sprayed with either non-reactive test formulation, positive control or water blank, ten insects in each case, and evaluated after 1 hour and 10 hours.
  • Example 13 Amplification of Reactive Emulsion Insecticidal Effect using Amino Acid derivatives.
  • N-Acetyl Cysteine NAC
  • PCA Pyrrolidone Carboxylic Acid
  • N-Acetyl Cysteine, CAS # 616-91-1 was obtained in powder form from BOC Sciences, Great Portland Street London, Catalogue number BO689-469 594.
  • the sodium salt of 2-Pyrrolidone-5-Carboxylic Acid, CAS # 54571-67-4 was obtained as a 50% solution in water from Thermo Fisher Scientific, Waltham, Ma, USA catalogue number 232921000.
  • NAC and PCA have slightly basic pH in solution.
  • Reactive Emulsions of this invention are acidic and are kept at or below pH 5.5 to retain reactivity. For this reason 0.1% W/W solutions of NAC and PCA were prepared in 50mM sodium citrate buffer at pH 5.0 and reduced fatty acid Reactive Emulsion concentrate (Table 15) was added to these at 5% by weight.
  • NAC and PCA controls were prepared by dissolving 0.1% of each in 50mM sodium citrate buffer reduced fatty acid Reactive Emulsions were used to illustrate the additive effect of NAC and PCA because the rate of activity of higher concentration fatty acid Emulsions would swamp the effect.
  • Emulsion concentrate A 5% by weight suspension of Emulsion concentrate was prepared in 50mM sodium citrate buffer without either NAC or PCA was prepared as a negative control and 50mM buffer on its own was used as a blank.
  • the Oriental Cockroach Blata Orientalis was used to evaluate the efficacy of the NAC and PCA supplemented reactive emulsion and the experimental design was the same as in Example 1. Individual insects were lifted with tweezers and sprayed with either NAC or PCA supplemented test formulations, negative control or buffer blank, ten insects in each case, and evaluated after 1 hour and 10 hours.
  • a 5% W/W dispersion of reduced fatty acid Reactive Emulsion in 50mM citrate buffer was shown to have 20% efficacy in 1 hour and 30% efficacy after 10 hours.
  • Example 16 Compositions of Free Fatty acids
  • Fatty Acids with carbon chain length from 4 to 22 were investigated. If the Fatty Acid melting point is greater than physiological temperatures at the site of action, the oil phase will be a solid and will react very slowly to any pH change which will in turn limit the rate of collapse and delivery of phase inverting amphipath.
  • a combination of a low and high melting point fatty acid will depress the melting point of the higher entity and so compositions of free fatty acids with combined melting point approximating to the physiological temperature of the site of action may be generated.
  • Table 17 provides a range of free fatty acid with utility in this invention together with their individual melting points.
  • the 16 carbon saturated palmitic acid has a melting point of 63 °C.
  • a similar 16 carbon unsaturated palmitoleic acid with one unsaturated carbon bond has a melting point of -0.1°C.
  • the saturated 18 carbon Stearic acid has a melting point of 70°C, but adding one, two or three unsaturated bonds (Oleic to linolenic) progressively decreases melting point to -11°C.
  • a combination of equal parts of stearic and linolenic acid has a combined melting point of 35°C, which can be decreased further by increasing the relative concentration of linolenic.
  • Equally low melting point triglyceride oils such as Miglyol 812 with a melting point of 6°C can be used in combination with high melting point fatty acids to reduce the combined melting point to useable physiological temperatures.
  • Insecticidal efficacy was demonstrated against the cockroach Blata Orientalis using the method described in Example 1, part 1 and a 10% dispersion of the Lauric / Palmitoleic reactive emulsion in water.

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  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

L'invention concerne des compositions comprenant des émulsions réactives d'acides gras libres et des lipides membranaires et leur utilisation dans la lutte contre les insectes et/ou les arachnides, et en particulier, des organismes hématophages qui peuvent agir en tant que vecteurs pour une grande variété d'agents pathogènes. Les compositions de la présente invention sont également utiles pour la modification de la réponse physiologique et/ou immunologique d'un sujet à, par exemple, une morsure d'un organisme hématophage, ainsi que le traitement et/ou la prévention d'une maladie provoquée par tout pathogène transmis par l'organisme audit sujet.
PCT/IB2024/052873 2023-03-30 2024-03-26 Compositions insecticides et arachnicides et utilisations associées Pending WO2024201283A1 (fr)

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