Compositions and methods for managing pest infections in companion animals

Abstract

The present disclosure provides a method for reducing, preventing, or controlling parasitic infection or infestation in a companion animal. The method comprises providing an animal feed comprising a pest control agent, and administering the animal feed to one or more companion animals during infection or infestation for 1 to 20 days. The method may comprise wherein the pest control agent comprises an Azadirachtin A enriched Azadirachtin A extract, and wherein the concentration of Azadirachtin A administered to the companion animal by the animal feed may comprise 0.01 mg to 5 mg Azadirachtin A / kg body weight per day. Other aspects are also included herein.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 381,357, filed October 28, 2022, and entitled "COMPOSITIONS AND METHODS FOR THE MANAGEMENT OF PEST INFECTIONS IN COMPANION ANIMALS", which is hereby incorporated by reference in its entirety. Technical Field

[0003] The present disclosure relates to compositions and methods for reducing, preventing, or controlling pest infections or infestations in companion animals. Specifically, the present disclosure provides compositions and methods for reducing, preventing, or controlling pest infections or infestations by administering one or more pest control agents as an in - feed or a supplement composition to various types of companion animals. Background Art

[0004] If left uncontrolled, parasitic infections and infestations in companion animals can affect the long - term health and welfare of the animals. The most common parasites that cause harm to companion animals include various arthropods, commonly known as fleas, ticks, mites, worms, flies, or lice. These parasites can themselves cause disease or can act as vectors for the transmission of microbial diseases in companion animals. It is very important to mitigate the negative impacts of such pests in order to protect the health of the animals and provide their well - being. It is also very important to control such pests to eliminate the possibility of zoonotic disease transmission.

[0005] There are many pharmaceutical formulations for controlling parasites in companion animals. These can include topical products or veterinary drugs, including ivermectin or imidacloprid. Many of these types of agents are of synthetic origin. The delivery mechanisms of such agents can pose challenges to caregivers and animals. Injectable agents can be painful for the animals and can pose unique challenges to the owners of companion animals due to unfamiliarity with the handling of syringes and needles, as well as when calculating the dosage requirements for administration. Further, the administration of oral medications can be cumbersome and the owners of companion animals may forget. Additionally, synthetic single - molecule drugs may lose efficacy over years of use. Finally, many products on the market can cause adverse reactions in animals, including vomiting, diarrhea, ataxia, and in severe cases, convulsions. Therefore, there is a need to provide a safe and effective management method that can mitigate the various pests that afflict companion animals. Such agents should have limited side effects on the health and well - being of the animals and should be convenient for animal owners to use and manage. Summary of the Invention

[0006] The present disclosure provides methods for reducing, preventing or controlling parasitic infections or infestations in companion animals. The method includes providing an animal feed comprising a pest control agent, and administering the animal feed to one or more companion animals during an infection or infestation for 1 day to 20 days. The method includes where the pest control agent comprises an Azadirachta indica extract rich in azadirachtin A, and where the concentration of azadirachtin A administered to the companion animal via the animal feed can include 0.01 mg to 5 mg azadirachtin A / kg body weight / day.

[0007] In one aspect, the method further includes where the one or more companion animals include one or more of cats, dogs or horses.

[0008] In one aspect, the method further includes where the Azadirachta indica extract rich in azadirachtin A comprises 15 wt% to 33 wt% azadirachtin A.

[0009] In one aspect, the method further includes where the parasitic infection or infestation is caused by one or more arthropod organisms.

[0010] In one aspect, the method further includes where the arthropod organisms include one or more fleas, ticks, mites, worms, flies or lice.

[0011] In one aspect, the method further includes where the parasitic infection or infestation is caused by one or more mites, the one or more mites including Dermatophagoides farinae, Dermatophagoides pteronyssinus or Tyrophagus putrescentia.

[0012] In one aspect, the method further includes where the parasitic infection or infestation is caused by yeast from the genus Malassezia.

[0013] In one aspect, the method further includes where the parasitic infection or infestation is caused by one or more worm species, the one or more worm species including heartworms, tapeworms, hookworms and whipworms.

[0014] In one aspect, the method further includes wherein the parasite infestation is caused by one or more flea species, the one or more flea species including Ctenocephalides canis, Ctenocephalides felis felis, Echidnophaga gallinacean, Pulex irritans, Pulex simulans, Spilopsyllus cuniculi, and Xenopsylla cheopis.

[0015] In one aspect, the method further includes wherein the parasite infestation is caused by one or more louse species, the one or more louse species including Damalinia equi, Haematopinus asini, Felicola subrostrate, Linognathus setosus, Trichodectes canis, and Heterodoxus spiniger.

[0016] In one aspect, the method further includes wherein the parasite infestation is caused by one or more tick species, the one or more tick species including Amblyomma Americanum, Rhipicephalus sanguineus, Amblyomma maculatum, Dermacentor reticulatus, Dermacentor variabilis, Ixodes holocyclus, Ixodes pacificus, Ixodes ricinus, and Ixodes scapularis.

[0017] In one aspect, the method further includes wherein the concentration of the pest control agent is configured to produce an inhibitory effect, the inhibitory effect including one or more of an anti - parasitic effect, an antibacterial effect, an antiviral effect, an antifungal effect, or an antiprotozoal effect.

[0018] In one aspect, the method further includes wherein the neem extract rich in azadirachtin A does not contain neem oil.

[0019] In one aspect, the method further includes wherein the animal feed further comprises one or more components selected from the group consisting of: antibiotic agents, antibacterial agents, antifungal agents, antiviral agents, antiparasitic agents, or antiprotozoal animal agents.

[0020] In one aspect, the method further includes wherein the pest control agent is provided in the animal feed in an amount effective to modulate the behavior of the pest.

[0021] In one aspect, the method further includes wherein modulating the behavior of the pest includes one or more of the following: a change in feeding habit, a change in feeding pattern, a change in appetite, a change in movement pattern, a change in mating pattern, a change in development, or a change in fertility as compared to the pests found on control animals not fed the pest control agent.

[0022] In one aspect, the method further includes wherein the change in the feeding pattern includes a decrease in the feeding pattern.

[0023] In one aspect, the method further includes wherein the change in appetite includes a decrease in appetite.

[0024] In one aspect, the method further includes wherein the change in movement includes a decrease in movement.

[0025] In one aspect, the method further includes wherein the change in mating pattern includes a decrease in the mating pattern.

[0026] In one aspect, the method further includes wherein the change in development includes an inhibition of development.

[0027] In one aspect, the method further includes wherein the change in fertility includes inhibition or delay of egg laying, inability to produce viable eggs, or a decrease in the total number of pregnant female pests.

[0028] In one aspect, the method further includes wherein the pest control agent is provided in the animal feed in an amount effective to modulate the pest by reducing the number of live pests present on the animal or in the animal's habitat as compared to the pests found on control animals not fed the pest control agent.

[0029] The present disclosure provides a method for reducing, preventing, or controlling parasitic infections or infestations in companion animals. The method can include: providing a pest control agent composition comprising a pest control agent, the pest control agent comprising neem extract rich in azadirachtin A; and administering the pest control agent composition to one or more companion animals during an infection or infestation for 1 day to 20 days. The method can further include wherein the concentration of azadirachtin A administered to the companion animal through the pest control agent composition is about 0.01 mg to 5 mg of azadirachtin A / kg body weight / day.

[0030] In one aspect, the method further includes wherein the pest control agent composition comprises a veterinary medicine product.

[0031] In one aspect, the method further comprises wherein the pest control agent composition comprises a dietary supplement.

[0032] In one aspect, the method further comprises wherein administering the pest control agent comprises administering the pest control agent once to three times per day.

[0033] In one aspect, the method further comprises wherein the pest control agent composition is administered to the animal for 14 days.

[0034] In one aspect, the method further comprises wherein the one or more companion animals include one or more of cats, dogs, or horses.

[0035] In one aspect, the method further comprises wherein the neem extract rich in azadirachtin A comprises 15 wt% to 33 wt% azadirachtin A.

[0036] The present disclosure provides a neem extract rich in azadirachtin A for reducing, preventing, or controlling parasitic infections or infestations in companion animals by following steps including: providing an animal feed comprising a pest control agent; and administering the animal feed to one or more companion animals during an infection or infestation for 1 day to 20 days. The present disclosure includes wherein the pest control agent comprises a neem extract rich in azadirachtin A; and wherein the concentration of azadirachtin A administered to the companion animal via the animal feed is about 0.01 mg to 5 mg azadirachtin A / kg body weight / day. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Not applicable. DETAILED DESCRIPTION

[0038] Certain aspects of the disclosed subject matter will now be described in detail. While the disclosed subject matter will be described in connection with the enumerated claims, it should be understood that the illustrated subject matter is not intended to limit the claims to the disclosed subject matter.

[0039] As described above, companion animals are typically infected with one or more arthropod parasite species. These parasites can commonly cause painful diseases and conditions in animals, and as a result, animal owners typically seek safe and effective control measures. While there are various chemical agents that target specific pests, the use of chemical agents typically has limitations, including owner and animal compliance, technical challenges in delivering various dosage forms, and limitations in long-term efficacy. Further, many chemical agents are specific to only one disease, condition, or parasite species, and thus many different active agents are needed to address the numerous arthropods that cause disease or other medical conditions. Accordingly, there is a need for a composition and method that specifically targets a wide range of arthropods that infect companion animal species and is highly effective and safe for use across species. The present disclosure provides compositions and methods for reducing, preventing, or controlling parasite infection or infestation in companion animals. In various aspects, the present disclosure relates to companion animals, including cats, dogs, and horses. The present disclosure provides plant-based pest control agents in the compositions herein.

[0040] As used herein, the term "infection" can refer to a condition in which a pest (including various pests as defined herein) can invade any internal or external part of a host organism, thereby harming the host organism, and the pest uses the components of the host organism to sustain itself, reproduce, or colonize the host organism.

[0041] As used herein, the term "infestation" can refer to the presence of an abnormal number of pests as defined herein, where these pests are concentrated in an area in numbers that can cause damage or disease by infecting the host organism.

[0042] As used herein, the term "pest" can refer to any organism that is harmful to the health, value, or appearance of another organism. The term pest can include, but is not limited to, one or more of various parasites, including worms, helminths, flukes, fleas, flies, lice, mites, ticks; one or more bacteria; one or more viruses; one or more types of fungi; and various protozoa (e.g., amoeba).

[0043] As used herein, the term "parasite" can refer to one or more ectoparasites or endoparasites. As used herein, the term "endoparasite" can refer to an organism that inhabits one or more internal niches of another organism. For example, an endoparasite can inhabit one or more of the tissues, organs, or systems of a host organism. For example, an endoparasite can inhabit any one of the small intestine, large intestine, esophagus, sinus, blood, bladder, kidney, stomach, brain, liver, and heart of a host organism. As used herein, the term "ectoparasite" can refer to an organism that inhabits or occupies an external niche of another species. For example, an ectoparasitic organism can inhabit or occupy the surface of a host species. Ectoparasites can inhabit the skin of an animal and the mucous membranes of the eyes, nasal cavity, ears, and mouth or any combination thereof. Parasites can include species belonging to the phylum Arthropoda.

[0044] As used herein, the term "pest control agent" can refer to an agent for reducing, preventing, or controlling an infection or infestation caused or contributed to by one or more pests. In various aspects, the pest control agents described herein can refer to agents for reducing, preventing, or controlling an infection or infestation caused by one or more endoparasites or ectoparasites.

[0045] Companion animal

[0046] The animal feed and pest control agent compositions herein can be adapted for administration to one or more animal species selected from the group consisting of dogs, cats, and horses. The animal feed and pest control agent compositions herein can be administered to animals at any developmental stage and any life stage. Although most aspects herein relate to companion animals including dogs, cats, and horses, it should be understood that companion animal can be a broad term intended to encompass many animal species. For example, companion animals can also include animals such as rabbits, mice, rats, hamsters, gerbils, guinea pigs, chinchillas, and ferrets.

[0047] The animal feed and pest control agent composition of the present invention can be formulated for canines of any suitable species and used at any life stage. As used herein, the term "dog" refers to domesticated dog-like animals of the Canidae family, including animals raised as companion animals, competition animals, breeding animals, etc. The animal feed and pest control agent composition of the present invention can be formulated for dogs of any suitable species and used at any life stage. Domestic dogs (Canis familiaris or Canis lupus familiaris) suitable for administering the animal feed and pest control agent composition of the present invention may include, but are not limited to, breeds including the following: Affenpinscher, Afghan Hound, Airedale Terrier, Akita, Alaksan Klee Kai, Alaskan Malamute, American Bulldog, American English Coonhound, American Eskimo, American Foxhound, American Hairless Terrier, American Leopard Hound, American Staffordshire Terrier, American Water Spaniel, Anatolian Shepherd, Appenzuller Sennenhund, Australian Cattle Dog, Australian Kelpie, Australian Shepherd, Australian Stumpy Tail Cattle Dog, Australian Terrier, Azawakh, Bargodo da Terceira, Barbet, Basenji, Basset Fauve de Bretagne, Basset Hound, Bavarian Mountain ScentHound), Beagle, Bearded Collie, Beauceron, Bedlington Terrier, Belgian Laekenois, Belgian Malinois, Belgian Sheepdog, Belgian Tervuren, Bergamasco Sheepdog, Berger Picard, Bernese Mountain, Bichon Frise, Biewer Terrier, Black and Tan Coonhound, Black Russian Terrier, Bloodhound, Bluetick Coonhound, Boerboel, Bohemian Shephard, Bolognese, Border Collie, Border Terrier, Borzoi, Boston Terrier, Bouvier des Flandres, Boxer, Boykin Spaniel, Bracco Italiano, Braque du Bourbonnais, Braque Francis Pyrenean, Briard, Brittany, Broholmer, Brussels Griffon, Bull (Bull Terrier), Bulldog, Bullmastiff, Cairn Terrier, Canaan, Cane Corso, Cardigan Welsh Corgi, Carolina, Catahoula Leopard, Caucasian Shepherd, Cavalier King Charles Spaniel, Central Asian Shepherd, Cesky Terrier, Chesapeake Bay Retriever, Chihuahua, Chinese Crested, Chinese Shar-Pei, Chinook, Chow Chow, Cirneco dell’Etna, Clumber Spaniel, Cocker Spaniel, Collie, Coton de Tulear, Croation Sheepdog, Curly-Coated Retriever, Czechoslovakian Vlcak, Dachshund, Dalmation, Dandie Dinmont Terrier, Danish-Swedish Farmdog, Deutscher Wachtelhund, Doberman Pinscher, Dogo Argentino, Dogue de Bordeaux, Drentsche Patrijshond, Drever, Dutch Shepherd, English Cocker Spaniel, English Foxhound, English Setter, English Springer Spaniel, English ToySpaniel), Entlebucher Mountain Dog, Estrela Mountain Dog, Euraiser, Field Spaniel, Finnish Lapphund, Finnish Spitz, Flat-Coated Retriever, French Bulldog, French Spaniel, German Longhaired Pointer, German Pinscher, German Shepherd, German Shorthaired Pointer, German Spitz, German Wirehaired Pointer, Giant Schnauzer, Glen of Imaal Terrier, Golden Retriever, Gordon Setter, Grand Basset Griffon, Vendéen, Great Dane, Great Pyrenees, Greater Swiss Mountain Dog, Greyhound Hamiltonstovare, Hanoverian Scenthound, Harrier, Havanese, Hokkaido, Hovawart, Ibizan Hound, Icelandic Sheepdog, Irish Red and White Setter, Irish Setter, Irish Terrier, Irish Water Spaniel, Irish Wolfhound, Italian Greyhound, Jagdterrier, Japanese Akita Inu, Japanese ChinChin), Japanese Spitz, Japanese Terrier, Jindo, Kai Ken, Karelian Bear Dog, Keeshond, Kerry Blue Terrier, Kishu Ken, Komondor, Kromfohrlander, Kuvasz, Labrador Retriever, Lagotto Romagnolo, Lakeland Terrier, Lancashire Heeler, Lapponian Herder, Leonberger, Lhasa Apso, Lowchen, Maltese, Manchester Terrier (standard and toy), Mastiff, Miniature American Shepherd, Miniature Bull Terrier, Miniature Pinscher, Miniature Schnauzer, Mountain Cur, Mudi, Neapolitan Mastiff, Nederlandse Kooikerhondje, Newfoundland, Norfolk Terrier, Norrbottenspets, Norwegian Buhund, Norwegian Elkhound, Norwegian Lundehund, Norwich Terrier, Nova Scotia Duck Tolling Retriever, Old English Sheepdog, Otterhound, Papillon, Parson Russell Terrier, Pekingese, Pembroke WelshCorgi), Perro de Presa Canario, Peruvian Inca Orchid, Petit Basset Griffon Vendeen, Pharaoh Hound, Plott Hound, Pointer, Polish Lowland Sheepdog, Pomeranian, Poodle (miniature, standard, and toy), Porcelaine, Portuguese Podengo, Portuguese Podengo Pequeno, Portuguese Pointer, Portuguese Sheepdog, Portuguese Water Dog, Pudelpointer, Pug, Puli, Pumi, Pyrenean Mastiff, Pyrenean Shepherd, Rafeiro do Alentejo, Rat Terrier, Redbone Coonhound, Rhodesian Ridgeback, Romanian Carpathian Shepherd, Romanian Mioritic Shepherd, Rottweiler, Russel Terrier, Russian Toy, Russian Tsvetnaya Bolonka, Saint Bernard, Saluki, Samoyed, Schapendoes, Schipperke, Scottish Deerhound, Scottish Terrier, Sealyham Terrier, Segugio Italiano, Shetland Sheepdog, Shiba Inu, ShihTzu), Shikoku, Siberian Husky, Silky Terrier, Skye Terrier, Sloughi, Slovakian Wirehaired Pointer, Slovenský Cuvac, Slovensky Kopov, Small Münsterländer, Smooth Fox Terrier, Soft Coated Wheaten Terrier, Spanish Mastiff, Spanish Water Dog, Spinone Italiano, Stabyhoun, Staffordshire Bull Terrier, Standard Schnauzer, Sussex Spaniel, Swedish Lapphund, Swedish Vallhund, Taiwan Dog, Teddy Roosevelt Terrier, Thai Ridgeback, Tibetan Mastiff, Tibetan Spaniel, Tibetan Terrier, Tornjak, Tosa, Toy Fox Terrier, Transylvanian Hound, Treeing Tennessee Brindle, Treeing Walker Coonhound, Vizsla, Volpino Italiano, Weimaraner, Welsh Springer Spaniel, Welsh Terrier, West Highland White Terrier, Wetterhoun, Whippet, Wire Fox Terrier, Wirehaired PointingGriffon, Wirehaired Vizsla, Working Kelpie, Xoloitzcuintli, Yakutian Laika, and Yorkshire Terrier.

[0048] The animal feed and pest control agent composition of the present invention can be formulated for felines of any suitable species and used at any suitable life stage. In various aspects, the animal feed and pest control agent composition of the present invention can be formulated for felines of any suitable species after weaning. As used herein, the term "cat" refers to domesticated cat-like animals, including animals raised as companion animals, competition animals, breeding animals, etc. The animal feed and pest control agent composition of the present invention can be formulated for domestic cats of any suitable species and used at any life stage. Domestic cats (Felis catus) suitable for administering the animal feed and pest control agent composition of the present invention may include, but are not limited to, breeds including the following: Abyssinian, American Bobtail, American Curl, American Shorthair, American Wirehair, Balinese, Bengal, British Shorthair, Birman, Bombay, Burmese, Burmilla, Calico, Canadian Sphinx, Chartreux, Chausie, Cornish Rex, Cymric, Devon Rex, Domestic Long Hair, Domestic Medium Hair, Domestic Shorthair, Elf, Egyptian Mau, Exotic Shorthair, Havana, Himalayan, Japanese Bobtail, Javanese, Korat, Kurilian Bobtail, LaPerm, Lykoi, Maine Coon, Manx, Munchkin, Nebelung, Norwegian,Forest), Ocicat, Oriental Short Hair, Persian, Pixie-bob, Ragamuffin, Ragdoll, Russian Blue, Savannah, Scottish Fold, Selkirk Rex, Siamese, Siberian, Singapura, Snowshoe, Somali, Sphynx, Tabby, Tonkinese, Tortoiseshell, Toyger, Turkish Angora, Turkish Van, Tuxedo, York Chocolate or any of their hybrids.,

[0049] The animal feed and pest control agent compositions of the present disclosure can be formulated for equines of any suitable species and used at any suitable life stage. As used herein, the term "horse" refers to domesticated hoofed animals, including animals raised as companion animals, racing animals, breeding animals, etc. Horses can include horses at any life stage, and those animals including foals, juveniles, mature, and senior animals. Domestic horses (Equus ferus caballus) suitable for administration of the animal feed and pest control agent compositions of the present disclosure can include, but are not limited to, breeds including the following: Akhal-Teke, American Paint, American Quarter, Andalusian, Appaloosa, Arabian, Black Forest, Clydesdale, Draft, Friesian, Hotblood, Icelandic, Miniature, Morgan, Mongolian, Mustang, Pony, Selle Francias, Shetland Pony, Standardbred, Tennessee Thoroughbred, Walker, and Warmblood. It should be understood that for the purposes of the present disclosure, donkeys and mules can further be included as companion equines.

[0050] Target pest

[0051] Pests common to companion animals and targeted by the pest control agents and animal feeds of the present disclosure can include various parasites, including parasites belonging to the phylum Arthropoda. These pests can include any number of flea, tick, mite, worm, fly, or louse species. In many cases, the arthropods infecting companion animals can themselves cause disease or can be vectors for various microorganisms, including bacteria, fungi, or viruses. The pest control agents described herein can reduce, prevent, or control infections or infestations caused by any of these pests. Although some of the pests are understood to be specific parasites for a particular host, many of the pests can infect or infest more than one companion animal species and are therefore not limited to a particular host.

[0052] Fleas susceptible to the pest control agents and feeds of the present disclosure may include those of the order Siphonaptera. Fleas infecting or infesting one or more of the companion animals of the present disclosure may include, but are not limited to, Ctenocephalides canis, Ctenocephalides felis, Ceratophyllus gallinae, Pulex irritans, Pulex simulans, Spilopsyllus cuniculi, Tunga penetrans, and Xenopsylla cheopis. Fleas can cause various diseases in animals, including but not limited to flea allergic dermatitis, tapeworms, anemia, bartonellosis, rickettsial diseases, and mycoplasmal diseases.

[0053] Ticks susceptible to the pest control agents and feeds of the present disclosure may include those of the order Ixodida. Ticks infecting or infesting one or more of the companion animals of the present disclosure may include, but are not limited to, Amblyomma americanum (i.e., lone star tick), Amblyomma maculatum, Dermacentor reticulatus (i.e., cattle tick or ornate dog / cattle tick), Dermacentor variabilis (i.e., wood tick or dog tick), Ixodes holocyclus, Ixodes pacificus, Ixodes ricinus, Ixodes scapularis (i.e., blacklegged tick or deer tick), and Rhipicephalus sanguineus (i.e., brown dog tick). It should be understood that the genus Rhipicephalus was previously classified as the genus Boophilus.

[0054] There are a large number of mite species worldwide that can infect or infest various companion animals. Mites suitable for targeting with the pest control agents and feeds of the present disclosure are generally divided into two arachnid orders, including Acariformes and Parasitiformes. Exemplary mites that can infect or infest one or more of the companion animals of the present disclosure may include, but are not limited to: Cheyletiella blakei, Cheyletiella yasguri, Cheyletiella spp., Chorioptes equi, Demodex canis, Demodex cati, Demodex equi, Demodex gatoi, Dermatophagoides farinae, Dermatophagoides pteronyssinus, Notoedres cati, Otodectes cynotis, Psoroptes equi, Sarcoptes scabiei, Trombicula alfreddugesi, Trombicula autumnalis, and Tyrophagus putrescentiae. In various aspects, diseases or infections caused by the mites of the present disclosure include several types of sarcoptic mange, including canine sarcoptic mange, feline sarcoptic mange (i.e., notoedic mange), otodectic mange, cheyletiellosis, and trombiculid dermatitis. In a specific aspect, the parasitic infection or infestation is caused by one or more mites including Dermatophagoides farinae, Dermatophagoides pteronyssinus, or Tyrophagus putrescentiae.

[0055] Parasitic worms are a common problem infecting companion animals worldwide. Worms susceptible to the pest control agents of the present text can include, but are not limited to, those commonly known as heartworms, tapeworms, hookworms, pinworms, nematodes, roundworms, and whipworms. The various parasitic worm species that can infect or infest one or more of the companion animals of the present text can include, but are not limited to, Ancylostoma caninum, Ancylostoma braziliense, Baylisascaris procyonis, Dictyocaulus arnfieldi, Dipylidium caninum, Dirofilaria immitis, Parascarisequorum, Onchocerca cervcalis, Oxocara canis, Oxyuris equi, Strongyloides westeri, Strongylus vulgaris, Strongylus endentatus, Strongylus equinus, Taenia crassiceps, Taenia serialis, Taenia ovis, Toxascaris canis, Toxascaris leonine, and Uncinariastenocephala. Worms that can infect horses can include one or more of the following: large strongyles of the genus Strongyles, small strongyles of the genus Cyathostomes, roundworms of the genus Ascarids, pinworms of the genus Oxyuris, nematodes of the genus Strongyloides, tapeworms of the genus Cestodes, lungworms such as Dictyocaulus arnfieldi, and horse fly larvae of the genus Gastrophilus.

[0056] Flies susceptible to the pest control agents and feeds herein may include those of the order Diptera. Flies that can infect or infest one or more of the companion animals herein may include, but are not limited to, mosquitoes, midges, sand flies, black flies, horse flies, deer flies, tsetse flies, blow flies, stomach flies, louse flies, etc. of various species. Exemplary flies that can infect the animals herein may include one or more of the following: the western horn fly (Haematobia irritans irritans) (i.e., horn fly), the autumn house fly (Musca autumnalis) (i.e., face fly), the stable fly (Stomoxys calcitrans) (i.e., biting stable fly), deer flies of the genus Chrysops and Diachlorus, and the deer ked (Lipoptena cervi). In various aspects, the pests herein may also refer to flies from the order Diptera.

[0057] Lice are generally host-specific pests and do not infect across animal species. Lice that can infect or infest one or more of the companion animals herein may include, but are not limited to, horse biting lice, donkey blood lice, cat biting lice, dog biting lice, dog chewing lice, and spiny kangaroo lice.

[0058] Fungal pests susceptible to the pest control agents herein may include one or more yeast species, including one or more species from the genus Malassezia. Malassezia species that can infect or infest one or more of the companion animals herein may include, but are not limited to, Malassezia furfur, Malassezia pachydermatis, Malassezia sympodialis, Malassezia globosa, Malassezia obtusa, Malassezia restricta, Malassezia slooffiae, Malassezia equina, Malassezia dermatis, Malassezia japonica, Malassezia nana, Malassezia capre, Malassezia yamatoensis, and Malassezia cuniculi.

[0059] Pest control agent

[0060] The pest control agents suitable for use in animal feed and the pest control agent compositions herein can have an adverse effect on pests that feed on the host. It should be understood that when a host animal ingests a pest control agent as a component of its daily diet over a given exposure duration, the pest control agent can be transferred to the body of the pest when the pest feeds on the host. The pest control agent can include any active ingredient or active agent that affects, promotes, or contributes to the eradication or reduction of pest infestation or pest infestation in an animal or group of animals. Additionally, as a result of reducing, preventing, or controlling the infestation or infestation, a suitable pest control agent can alleviate or improve one or more symptoms associated with pest infestation or pest infestation. The pest control agents used herein can be biologically active against one or more animal pests and one or more animal species.

[0061] It should be understood that when a companion animal ingests the pest control agent described herein, the pest control agent is distributed systemically throughout the tissues and body fluids of the animal. The pest can be exposed to the pest control agent after ingesting the pest control agent through the skin, meat, blood, mucus, mucous membranes, or other tissues of the host organism. Modulation of the pest (such as modulation of pest behavior and life cycle) occurs to reduce, prevent, or control pest infestation or pest infestation in the companion animal. In various aspects, the pest can be repelled or killed by the pest control agent herein. Thus, the pest control agent herein can be provided to the pest in an amount effective to modulate pest behavior in animal feed or a pest control agent composition.

[0062] The modulation of the pest can have many effects on the pest population, including ultimately reducing the number of live pests that can infect or infest the host animal. The modulation of the pest can include modulation of pest mortality. It should be understood that modulation of pest mortality can include reducing the number of live pests present on the animal or in the animal's habitat. The modulation of the pest can also include modulation of pest behavior, including changes in feeding habits, feeding patterns, appetite, movement patterns, mating patterns, development, fertility, or any combination thereof compared to pests found on control animals not fed the pest control agent. Changes in feeding patterns can include a reduction in feeding patterns. Changes in appetite can include a decrease in appetite. Changes in movement can include a reduction in movement. Changes in mating patterns can include a reduction in mating patterns, which in turn can lead to a reduction in the development or production of offspring. Changes in development can include inhibition of development due to inhibition of the molting process, which results in a reduction in pest development or a delay in pest development. Changes in fertility can include inhibition or delay of egg laying, inability to produce viable eggs, or a reduction in the total number of pregnant female pests.

[0063] In various aspects, the modulation of pests can include altering the development of pests during their life cycle, including the modulation of growth or progression in a particular life stage, the modulation of growth or progression from one life stage to the next (e.g., modulating molting), the modulation of egg laying, the modulation of fertility, or any combination thereof. The modulation of growth or progression in a particular life stage can include halting the growth of an organism and preventing further physical development, including a reduction in body size or sexual development. In some aspects, the modulation of growth or progression from one life stage to the next can include preventing a pest from transitioning from one life stage to the next by inhibiting the molting process. The modulation of egg laying can include reducing the egg laying of females, which can further result in a reduction in the fertility of adult females. The modulation of fertility can include reducing the fertility of both female and male pests.

[0064] The animal feeds described herein can contain or be supplemented with one or more pest control agents. When the animal feed contains at least two or more different pest control agents, each pest control agent can be individually active (or bioactive) and capable of modulating one or more of the behavior, development, or fertility of pests. Alternatively, the pest control agent can be a component of a pest control agent composition that can be fed to the animal separately. Each pest control agent can be individually effective against one or more different pests as described herein.

[0065] The pest control agents suitable for use in the animal feeds and pest control agent compositions herein can contain one or more active agents, including synthetic or natural agents. The one or more synthetic or natural agents can include agents classified as active pharmaceutical ingredients, veterinary products, etc. In some aspects, the active agent of the pest control agent for use herein can be obtained from plants belonging to the genus Azadirachta. The pest control agent can be obtained or extracted from the neem tree (Azadirachta indica, a tree commonly referred to as "neem"). Extracts prepared from plants belonging to the genus Azadirachta (e.g., the neem tree) can contain potent terpenoid compounds, including one or more azadirachtinoid compounds. Azadirachtinoid compounds include azadirachtin compounds such as azadirachtin A, azadirachtin B, azadirachtin D, azadirachtin E, azadirachtin F, azadirachtin G, azadirachtin H, azadirachtin I, azadirachtin K, and / or other azadirachtin variants. Extracts from plants belonging to the genus Azadirachta can also contain varying amounts of many other components. In some aspects, the extract can contain additional compounds such as the limonoid compounds salannin, nimbin, deacetylsalannin, and 6-deacetylnimbin. In various aspects, the extract can also contain one or more azadirachtinoid compounds.

[0066] As used herein, the term "azadirachtin" may refer to a collective term applicable to a large group of active compounds and is intended to cover not only all naturally occurring variants or derivatives of azadirachtin, including but not limited to azadirachtin A, B, D, E, F, G, H, I, K, but also all synthetic variants, fragments, analogs, and derivatives thereof. In this regard, it should be understood that any azadirachtin variant, fragment, derivative, or analog used herein should be functional as they exhibit at least one of the inhibitory effects described.

[0067] Azadirachtin can be obtained or extracted from any part of the neem tree plant (including, for example, leaves, stems, bark, fruits, seeds, or any combination thereof) by one or more extraction processes. Suitable extraction methods may include techniques utilizing mechanical pressing of neem seeds (i.e., kernels) and the use of non-polar solvents. Various solvent extraction techniques using alcohol or water extraction processes, mechanical pressing, and non-polar extraction methods can be used to produce a pest control agent rich in azadirachtin A for use herein and are described in U.S. Patent No. 4,556,562, U.S. Patent No. 5,695,763, and U.S. Patent No. 11,096,404, the entire contents of which are incorporated herein by reference.

[0068] For example, azadirachtin can be effectively recovered from the seeds of the neem tree. Exemplary methods for recovering azadirachtin from neem seeds may include providing neem seeds, crushing the neem seeds, extracting azadirachtin from the crushed seeds with water, and then extracting azadirachtin from the water by adding a second extraction solvent, which includes a non-aqueous solvent that is immiscible with water and has a higher solubility of azadirachtin than water or a surfactant having a cloud point temperature between 20°C and 80°C. Concentrated azadirachtin can be recovered from the second extraction solution and exhibits high activity as an insecticide and anthelmintic. Extraction methods using polar solvents (e.g., water) produce extracts rich in polar components, such as azadirachtin compounds.

[0069] In various aspects, azadirachtin suitable for use herein includes azadirachtin A, the chemical name of which is dimethyl [2aR-[2aα,3β,4β(1aR*,2S*,3aS*,6aS*,7S*,7aS*),4aβ,5α,7aS*,8β(E),10β,10aα,10bβ]]-10-(acetoxy)octahydro-3,5-dihydroxy-4-methyl-8-[(2-methyl-1-oxo-2-butenyl)oxy]-4-(3a,6a,7,7a)-tetrahydro-6a-hydroxy-7a-methyl-2,7-methano-furo[2,3-b]oxireno[e]oxa -1a(2H)-yl)-1H,7H-naphtho-[1,8-bc:4,4a-c‘]difuran-5,10a(8H)-dicarboxylate.

[0070] Azadirachtin A is the most abundant among a group of azadirachtin compounds. Azadirachtin A accounts for about 80% of the azadirachtin compounds in the kernels of Azadirachta indica seeds. The structural formula of azadirachtin A is:

[0071]

[0072] The pest control agent of the present invention may comprise an Azadirachta indica extract, which is an aqueous extract. In various aspects, the Azadirachta indica extract may comprise an aqueous extract of Azadirachta indica seeds. The aqueous extract of Azadirachta indica seeds may comprise an aqueous extract of the kernels of Azadirachta indica seeds. The aqueous extract of the kernels of Azadirachta indica seeds may comprise an aqueous extract of the whole Azadirachta indica seeds (including the kernels and the seed coats of Azadirachta indica seeds). The aqueous extract of Azadirachta indica seeds may be in liquid form, or it may be dried to remove water to produce a powder form. For example, the Azadirachta indica extract of the present invention may comprise an aqueous extract of Azadirachta indica seeds or an aqueous extract of the kernels of Azadirachta indica seeds that has been dried into a powder.

[0073] It should be understood that the pest control agent described herein is not the same as the Azadirachta indica extract described as neem oil or solvent-preferred Azadirachta indica extract. In various aspects, compared with neem oil and other oil-based formulations, the pest control agent containing azadirachtin herein contains a richer active ingredient of azadirachtin compounds, and especially azadirachtin A. This is because azadirachtin compounds (such as azadirachtin A) are relatively polar complex terpenoids with a large number of oxygen functional groups, which makes the molecule have moderate water solubility (for example, the solubility is about 2 g / L). Therefore, compared with neem oil or solvent-preferred Azadirachta indica extract, azadirachtin compounds (such as azadirachtin A) are present in the extract obtained with a polar solvent at a much higher concentration. Without wishing to be bound by any particular theory, it is believed that the bioavailability of the active ingredient in the water-based extract of the azadirachtin A-rich extract of the present disclosure to the target parasite may be greater than that of the active ingredient in neem oil to the target parasite, because of the increased solubility and miscibility of the water-based extract in water. Therefore, the pest control agent herein does not comprise neem oil, is not composed of neem oil, or is not substantially composed of neem oil. The pest control agent for animal feed provided herein may comprise azadirachtin A, consist of azadirachtin A, or be substantially composed of azadirachtin A.

[0074] Pest control agents containing neem extract rich in azadirachtin A can include pest control agents having at least 15 wt% to 33 wt% azadirachtin A. In various aspects, pest control agents containing neem extract rich in azadirachtin A can include pest control agents having at least 20 wt% to 26 wt% azadirachtin A. In various aspects, pest control agents containing neem extract rich in azadirachtin A can include pest control agents having at least 28 wt% to 31 wt% azadirachtin A. In some aspects, pest control agents containing neem extract rich in azadirachtin A can include pest control agents having at least 29 wt% to 30 wt% azadirachtin A. In other aspects, pest control agents containing neem extract rich in azadirachtin A can include pest control agents having at least 34 wt% to 40 wt% azadirachtin A. In various aspects, pest control agents rich in azadirachtin A can include pest control agents having 30 ± 1 wt% azadirachtin A. In various aspects, pest control agents rich in azadirachtin A can include pest control agents having 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 20 wt%, 21 wt%, 22 wt%, 23 wt%, 24 wt%, 25 wt%, 26 wt%, 27 wt%, 28 wt%, 29 wt%, 30 wt%, 31 wt%, 32 wt% or 33 wt%, or any amount of pest control agent falling within any of the foregoing ranges. In still other aspects, pest control agents containing neem extract rich in azadirachtin A can include pest control agents having at least 34 wt% to 45 wt% or at least 38 wt% to 43 wt% azadirachtin A. As used herein, unless otherwise specified, the terms "neem extract rich in azadirachtin A" and "composition rich in azadirachtin A" can be used interchangeably. Exemplary compositions of neem extracts suitable for pest control agents rich in azadirachtin A herein can include the formulations outlined in Table 1.

[0075] Table 1. Exemplary azadirachtin A-rich pest control agent formulations

[0076] Neem seed extract composition % w / w Azadirachtin A 15-333 Azadirachtin B ≤19.0 Azadirachtin D ≤13.0 Azadirachtin E ≤5.0 Azadirachtin F ≤5.0 Azadirachtin G ≤5.0 Azadirachtin H ≤5.0 Azadirachtin I ≤5.0 Azadirachtin K and other azadirachtins ≤5.0 Total azadirachtin 52.0

[0077] A pest control agent containing neem extract rich in azadirachtin A may also contain various concentrations of other azadirachtin compounds. Azadirachtin compounds may include azadirachtin compounds such as azadirachtin B at ≤19.0% w / w, or ≤6.0% w / w, or 4.0 to 6.0% w / w, or 5.6% w / w to 6.0% w / w; azadirachtin D at ≤13.0% w / w, or ≤5.0% w / w, or 2.5 to 5.0, or 4.0% w / w to 5.0% w / w; azadirachtin E at ≤5.0% w / w, or 1.0% w / w to 5.0% w / w, or 1.5% w / w to 2.0% w / w; azadirachtin F at ≤5.0% w / w, or 1.0% w / w to 5.0% w / w, or 1.5% w / w to 2.0% w / w; azadirachtin G at ≤5.0% w / w, or 1.0% w / w to 5.0% w / w, or 1.5% w / w to 2.0% w / w; azadirachtin H at ≤5.0% w / w, or 1.0% w / w to 5.0% w / w, or 2.5% w / w to 4.0% w / w; azadirachtin I at ≤5.0% w / w, or 1.0% w / w to 4.0% w / w, or 1.5% w / w to 2.5% w / w; and azadirachtin K at ≤5.0% w / w, or 1.0% w / w to 5.0% w / w, or 2.5% w / w to 4.0% w / w and / or other azadirachtin variants. The extract may also contain azadirachtin at ≤5.0% w / w, or 1.0% w / w to 5.0% w / w, or 2.5% w / w to 4.0% w / w.

[0078] Exemplary pest control agents suitable for use herein may contain an aqueous extract of neem seeds that has been dried to a powder. The powder may include the appearance of a fine white powder. Exemplary pest control agents may contain azadirachtin A at a concentration of 17% to 37% by weight, azadirachtin B at a concentration of 0% to 19% by weight, and azadirachtin D at a concentration of 0% to 13% by weight. Exemplary pest control agents may also contain trace amounts of other limonoid compounds, including azadirachtin and salannin.

[0079] Exemplary pest control agents containing a composition rich in azadirachtin A include, but are not limited to (Coromandel, Intl. Ltd., Telangana, India) or Technical (Coromandel International Limited, Telangana, India) or any derivatives of their combination.

[0080] Animal feed

[0081] The present disclosure provides animal feeds to be used in companion animal diets. It should be understood that the animal feeds herein may include suitable types of animal feeds specific to a given animal species. The animal feeds can be used as components of diets fed to companion animals of any species identified herein. In various aspects, the animal feeds referred to herein can include complete and balanced animal feeds suitable for and customized for one or more of canines, felines, or equines. In some aspects, the animal feed is a canine feed. In some aspects, the animal feed is a feline feed. In some aspects, the animal feed is an equine feed.

[0082] Complete animal feeds can include nutritionally complete and balanced daily dietary compositions that are fed as the sole ration and can sustain life, promote growth, and maintain reproduction without the intake of any additional substances other than water. The animal feeds herein can include complete feeds. Complete animal feeds can contain a mixture containing appropriate levels of nutrients required to sustain animal life, these nutrients including proteins, fats, carbohydrates, and the like. Complete feeds can also contain a composite mixture containing various energy sources such as carbohydrates, proteins, and fats. In various aspects, the animal feeds herein can contain at least protein and starch. Additional ingredients necessary to support the life, growth, well-being, and reproduction of the animal can be included, such as vitamins and minerals.

[0083] The animal feeds herein can be in any suitable form, including dry solids, semi-solids, or liquids. The animal feeds of the present disclosure can be produced using a base feed formulation that uses raw materials that can be selected based on their application and for each given animal species. In various aspects, the animal feed is a dry solid feed. In some aspects, the animal feed is a semi-solid feed, wherein the semi-solid feed contains a liquid component and a solid component. In other aspects, the animal feed is a liquid feed. In still other aspects, the animal feed can contain both solid feed components and liquid feed components to be mixed at the time of feeding. In some aspects, the animal feed can be applied to the animal as a surface dressing applied to the daily feed ration or diet. In some aspects, the animal feed can be a liquid, such as a liquid spray for application to a base feed, a liquid water additive, a liquid irrigation agent, or a liquid water bath. It should be understood that the liquid irrigation agent as described herein can include one or more of a suspension, a solution, or an emulsion.

[0084] Animal feeds in solid form can include pellets, extruded blocks, steam pellets, flakes, tablets, powders, granules, crumbles, etc. Animal feeds in liquid form can include pastes, gels, aqueous solutions, oils, oil and water emulsions, slurries, suspensions, etc. In various aspects, the basal feed can include basal feed pellets. In some aspects, the basal feed pellets can contain a porous matrix distributed throughout. In various aspects, solid feeds (such as basal feed pellets) can also contain one or more oils, which are disposed on the surface or distributed throughout the animal feed. Animal feed can contain any substrate that is edible by the animal. For example, the edible substrate can provide a source of nutrition for the animal or can be an inert substrate that has no nutritional value for the animal.

[0085] The animal feeds herein can contain one or more pest control agents. In various aspects, the one or more pest control agents can be present in the animal feed in an amount effective to produce an inhibitory effect on one or more pests as compared to animals not fed the pest control agent. In various aspects, solid feeds (such as basal feed pellets) can also contain one or more pest control agents disposed on the surface or distributed throughout the animal feed, such as within an oil within a porous matrix on the outer surface of the basal feed pellets. In some aspects, the pest control agent can be applied to the animal as a surface dressing applied to the daily animal feed ration or diet. Thus, the animal feeds herein can contain pest control agents for controlling an infection or infestation caused by one or more pests. In various aspects, the animal feeds herein can contain pest control agents for controlling an endoparasite or ectoparasite infection or infestation.

[0086] Each pest control agent included in the animal feed herein may be individually capable of controlling one or more of parasite, bacterial, viral, fungal or protozoal infections or infestations. Thus, it should be understood that any given pest control agent for all aspects herein may be said to exhibit one or more inhibitory effects, including antiparasitic effects (e.g., antiectoparasitic, antiendoparasitic), antibacterial effects, antiviral effects, antifungal effects or antiprotozoal effects. In various aspects, compared to animals not fed the pest control agent, the pest control agents herein may be said to have inhibitory effects including antiparasitic effects, wherein the antiparasitic effects may further include antiectoparasitic effects, antiendoparasitic effects or both. It should be understood that compared to animals not fed the pest control agent, the inhibitory effects against one or more pests may include one or more effects for reducing, preventing, controlling or minimizing the concentration and spread of various parasite, bacterial, viral, fungal or protozoal organisms. In various aspects, the pest control agents of the present disclosure may produce inhibitory effects against one or more pests, including one or more effects for reducing, preventing, controlling or minimizing the concentration and spread of various endoparasites or ectoparasites. Reducing, preventing or controlling parasites may include completely preventing infection or infestation in an animal population or on each animal, reducing the total number of parasites present in an animal population or on each animal, or controlling how many parasites are present in an animal population or on each animal according to local regulatory requirements. It should be understood that the inhibitory effects described herein may be measured against an animal population infected or infested with one or more pests fed a diet lacking neem extract rich in azadirachtin A.

[0087] In other aspects, the suppression of pests may include one or more of antifeedant effects, antiecdysis effects, antifertility and antireproductivity effects, or antiparasitic effects. As used herein, "antifeedant effect" may refer to the effect of one or more pest control agents in stopping or inhibiting the feeding of pests, resulting in malnutrition, retarded development, blocked or delayed molting, and death of the pests. Malnourished pests are also less likely to effectively evade host immunity. As used herein, the term "antiecdysis" may refer to the effect of one or more pest control agents in preventing or delaying the molting process of pests. The molting process occurs when pests grow and shed their exoskeletons from one life stage to the next, and is controlled by hormones and neurons, and the pest control agents herein may exert one or more antiecdysis effects on pests. As used herein, the terms "antifertility effect" and "antireproductivity effect" are collectively referred to as "antifertility and antireproductivity effects", and may include one or more effects on male or female reproduction. It should be understood that the term "fertility" may refer to the actual number of offspring produced by a female or eggs released from a female, and the term "reproductivity" may refer to the biological potential for reproduction, and due to their close relationship, these two terms as used herein may be used interchangeably unless otherwise specified. Antifertility and antireproductivity effects may include reducing total gamete production in males and females, completely or partially inhibiting the production of viable eggs, altering the anatomy and morphology of male or female gametes, altering the potential for egg fertilization, and reducing the total number of gravid female pests.

[0088] In the form of application, the amount of the pest control agent contained in the animal feed herein can be about 0.01 grams to 100 grams of pest control agent / kg of animal feed (g / kg), about 90 g / kg of animal feed, about 80 g / kg of animal feed, about 70 g / kg of animal feed, about 60 g / kg of animal feed, about 50 g / kg of animal feed, about 40 g / kg of animal feed, about 30 g / kg of animal feed, about 20 g / kg of animal feed, about 1 g to 10 g / kg of animal feed, about 2 g to 9 g / kg of animal feed, about 3 g to 7 g / kg of animal feed, about 4 g to 6 g / kg of animal feed, or about 5 g / kg of animal feed.

[0089] In various aspects, the animal feed of the present disclosure can include a total amount of a pest control agent and / or an active ingredient in an amount effective to produce an inhibitory effect on one or more pests, including concentrations of about 0.01 g / kg of animal feed, 0.05 g / kg of animal feed, 0.1 g / kg of animal feed, 0.2 g / kg of animal feed, 0.3 g / kg of animal feed, 0.4 g / kg of animal feed, 0.5 g / kg of animal feed, 0.6 g / kg of animal feed, 0.7 g / kg of animal feed, 0.8 g / kg of animal feed, 0.9 g / kg of animal feed, 1.0 g / kg of animal feed, 1.25 g / kg of animal feed, 1.5 g / kg of animal feed, 1.75 g / kg of animal feed, 2.0 g / kg of animal feed, 2.25 g / kg of animal feed, 2.5 g / kg of animal feed, 2.75 g / kg of animal feed, 3.0 g / kg of animal feed, 5.0 g / kg of animal feed, 5.25 g / kg of animal feed, 5.5 g / kg of animal feed, 5.75 g / kg of animal feed, 6.0 g / kg of animal feed, 6.25 g / kg of animal feed, 6.5 g / kg of animal feed, 6.75 g / kg of animal feed, 7.0 g / kg of animal feed, 7.0 g / kg of animal feed, 7.25 g / kg of animal feed, 7.5 g / kg of animal feed, 7.75 g / kg of animal feed, 8.0 g / kg of animal feed, 8.25 g / kg of animal feed, 8.5 g / kg of animal feed, 8.75 g / kg of animal feed, 9.0 g / kg of animal feed, 9.25 g / kg of animal feed, 9.5 g / kg of animal feed, 9.75 g / kg of animal feed, 10.0 g / kg of animal feed, 15 g / kg of animal feed, 20 g / kg of animal feed, 25 g / kg of animal feed, 30 g / kg of animal feed, 35 g / kg of animal feed, 40 g / kg of animal feed, 45 g / kg of animal feed, 50 g / kg of animal feed, 55 g / kg of animal feed, 60 g / kg of animal feed, 65 g / kg of animal feed, 70 g / kg of animal feed, 75 g / kg of animal feed, 80 g / kg of animal feed, 85 g / kg of animal feed, 90 g / kg of animal feed, 95 g / kg of animal feed or 100 g / kg of animal feed, or any amount within any of the foregoing concentration ranges.

[0090] It should be understood that the above concentrations correspond to an amount of about 0.001% to 10% by weight (% w / w) of the total pest control agent relative to the animal feed. In various aspects, the animal feed herein may contain the total amount of the pest control agent, including 0.001% w / w, 0.002% w / w, 0.003% w / w, 0.004% w / w, 0.005% w / w, 0.006% w / w, 0.007% w / w, 0.008% w / w, 0.009% w / w, 0.010% w / w, 0.020% w / w, 0.030% w / w, 0.040% w / w, 0.050% w / w, 0.060% w / w, 0.070% w / w, 0.080% w / w, 0.090% w / w, 0.10% w / w, 0.11% w / w, 0.12% w / w, 0.13% w / w, 0.14% w / w, 0.15% w / w, 0.16% w / w, 0.17% w / w, 0.18% w / w, 0.19% w / w, 0.20% w / w, 0.21% w / w, 0.22% w / w, 0.23% w / w, 0.24% w / w, 0.25% w / w, 0.26% w / w, 0.27% w / w, 0.28% w / w, 0.29% w / w, 0.30% w / w, 0.31% w / w, 0.32% w / w, 0.33% w / w, 0.34% w / w, 0.35% w / w, 0.36% w / w, 0.37% w / w, 0.38% w / w, 0.39% w / w, 0.40% w / w, 0.41% w / w, 0.42% w / w, 0.43% w / w, 0.44% w / w, 0.45% w / w, 0.46% w / w, 0.47% w / w, 0.48% w / w, 0.49% w / w, 0.50% w / w, 0.51% w / w, 0.52% w / w, 0.53% w / w, 0.54% w / w, 0.55% w / w, 0.56% w / w, 0.57% w / w, 0.58% w / w, 0.59% w / w, 0.60% w / w, 0.61% w / w, 0.62% w / w, 0.63% w / w, 0.64% w / w, 0.65% w / w, 0.66% w / w, 0.67% w / w, 0.68% w / w, 0.69% w / w, 0.70% w / w, 0.71% w / w, 0.72% w / w, 0.73% w / w, 0.74% w / w, 0.75% w / w, 0.76% w / w, 0.77% w / w, 0.78% w / w, 0.79% w / w, 0.80% w / w, 0.81% w / w, 0.82% w / w, 0.83% w / w, 0.84% w / w, 0.85% w / w, 0.86% w / w, 0.87% w / w, 0.88% w / w, 0.89% w / w, 0.90% w / w, 0.91% w / w, 0.92% w / w, 0.93% w / w, 0.94% w / w, 0.95% w / w, 0.96% w / w, 0.97% w / w, 0.98% w / w, 0.99% w / w, 1.0% w / w, 2.0% w / w, 3.0% w / w, 4.0% w / w, 5.0% w / w, 6.0% w / w, 7.0% w / w, 8.0% w / w, 9.0% w / w or 10.0% w / w, or any amount within any of the foregoing ranges.

[0091] Animal feed may contain a variety of ingredients, including but not limited to meat, including poultry such as chickens, turkeys, geese, ducks, ostriches, quails, and pheasants; beef; buffalo; pork; mutton; venison; fish, including but not limited to whitefish, cod, pollock, salmon, and tuna; crustaceans; liver; or animal by-products. The animal feed herein may also contain grains such as wheat, rice, oats, soybeans, other grains, and their flours. The animal feed composition may also contain various fruits and vegetables, including but not limited to sweet potatoes, carrots, spinach, potatoes, peas, pumpkins, beets, squash, leafy greens, apples, berries, and corn. The animal feed herein may also contain seeds or legumes, including but not limited to chickpeas and chickpea flour, black beans, white beans, kidney beans, sunflower seeds, chia seeds and meal, flax seeds and meal, peas and pea flour, soybeans, and gluten derived from grains such as oats, barley, rice, corn, wheat, etc. The animal feed may also contain various oils and their fractions, including but not limited to vegetable oils, sunflower oil, safflower oil, canola oil, soybean oil, olive oil, and coconut oil, etc. The animal feed herein may also contain herbs, natural and artificial flavorants, spices, extracts, glycerin, tapioca starch, soy lecithin, sunflower lecithin, and natural preservatives.

[0092] In addition, vitamins and minerals can be added to the animal feed of the present invention. Exemplary vitamins and minerals can include, but are not limited to, vitamin A (retinol - acetate), vitamin D3 (cholecalciferol), vitamin E (DL-α-tocopherol), vitamin K3 (menadione), vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine - HCL), vitamin B7 (biotin), vitamin B9 (folic acid), vitamin B12 (cyanocobalamin)), minerals (e.g., calcium, phosphorus, potassium, sodium, chlorine, magnesium, iron, copper, manganese, zinc, iodine, selenium, monocalcium phosphate (CaH4P2O8), sodium bicarbonate (NaHCO3), sodium chloride (NaCl), potassium chloride (KCl), potassium iodide (KI)), amino acids (e.g., arginine, histidine, isoleucine, leucine, lysine, methionine, methionine - cystine, phenylalanine, phenylalanine - tyrosine, threonine, tryptophan, valine, taurine), ferrous sulfate (II) monohydrate (FeSO4.H2O); copper sulfate (CuSO4.5H2O); manganese (II) oxide (MnO); MnSO4.H2O; zinc sulfate (ZnSO4.H2O; Na2SeO3), choline chloride (C5H 14 ClNO), enzymes, and various combinations thereof. In various aspects, ferrous sulfate (II) monohydrate (FeSO4.H2O); copper sulfate (CuSO4.5H2O); manganese (II) oxide (MnO); MnSO4.H2O; zinc sulfate (ZnSO4.H2O; Na2SeO3), choline chloride (C5H 14 ClNO), enzymes can be included in chelated mineral form. For example, chelated minerals can include minerals chelated with one or more types of amino acids to facilitate animal absorption and uptake.

[0093] Animal feed containing azadirachtin A

[0094] The animal feed of the present disclosure may include animal feed supplemented with the pesticidal agent azadirachtin A. The animal feed may be administered as part of an animal feed diet to various companion animals to control arthropod pests. The animal feed may be at least partially coated on an outer surface with a composition enriched in azadirachtin A or may be completely coated on the outer surface with a composition enriched in azadirachtin A. In some aspects, the animal feed of the present disclosure may contain a composition enriched in azadirachtin A that is at least partially dispersed throughout the animal feed. In various aspects, a solid feed (such as a basal feed pellet) may also contain a composition enriched in azadirachtin A disposed on a surface or distributed throughout the animal feed, such as within an oil in a porous matrix disposed on an outer surface of the basal feed pellet. In various aspects, the animal feed of the present disclosure may be at least partially coated on an outer surface with a composition enriched in azadirachtin A and may also have a composition enriched in azadirachtin A that is at least partially dispersed throughout the animal feed. In various aspects, the animal feed may include one or more layers of a composition enriched in azadirachtin A on an outer surface.

[0095] The animal feed of the present disclosure may contain a composition enriched in azadirachtin A at a concentration of from about 0.01 grams to 100 grams per kilogram (g / kg) of animal feed, about 90 g / kg of animal feed, about 80 g / kg of animal feed, about 70 g / kg of animal feed, about 60 g / kg of animal feed, about 50 g / kg of animal feed, about 40 g / kg of animal feed, about 30 g / kg of animal feed, about 20 g / kg of animal feed, from about 0.01 g to 10 g / kg of animal feed, from about 1 g to 10 g / kg of animal feed, from about 2 g to 9 g / kg of animal feed, from about 3 g to 7 g / kg of animal feed, from about 4 g to 6 g / kg of animal feed, or about 5 g / kg of animal feed.

[0096] In various aspects, the animal feed of the present invention may comprise a composition rich in azadirachtin A at a concentration of about 0.01 g of composition rich in azadirachtin A / kg of animal feed (g / kg), 0.05 g / kg of animal feed, 0.1 g / kg of animal feed, 0.2 g / kg of animal feed, 0.3 g / kg of animal feed, 0.4 g / kg of animal feed, 0.5 g / kg of animal feed, 0.6 g / kg of animal feed, 0.7 g / kg of animal feed, 0.8 g / kg of animal feed, 0.9 g / kg of animal feed, 1.0 g / kg of animal feed, 1.25 g / kg of animal feed, 1.5 g / kg of animal feed, 1.75 g / kg of animal feed, 2.0 g / kg of animal feed, 2.25 g / kg of animal feed, 2.5 g / kg of animal feed, 2.75 g / kg of animal feed, 3.0 g / kg of animal feed, 5.0 g / kg of animal feed, 5.25 g / kg of animal feed, 5.5 g / kg of animal feed, 5.75 g / kg of animal feed, 6.0 g / kg of animal feed, 6.25 g / kg of animal feed, 6.5 g / kg of animal feed, 6.75 g / kg of animal feed, 7.0 g / kg of animal feed, 7.0 g / kg of animal feed, 7.25 g / kg of animal feed, 7.5 g / kg of animal feed, 7.75 g / kg of animal feed, 8.0 g / kg of animal feed, 8.25 g / kg of animal feed, 8.5 g / kg of animal feed, 8.75 g / kg of animal feed, 9.0 g / kg of animal feed, 9.25 g / kg of animal feed, 9.5 g / kg of animal feed, 9.75 g / kg of animal feed, 10.0 g / kg of animal feed, 15 g / kg of animal feed, 20 g / kg of animal feed, 25 g / kg of animal feed, 30 g / kg of animal feed, 35 g / kg of animal feed, 40 g / kg of animal feed, 45 g / kg of animal feed, 50 g / kg of animal feed, 55 g / kg of animal feed, 60 g / kg of animal feed, 65 g / kg of animal feed, 70 g / kg of animal feed, 75 g / kg of animal feed, 80 g / kg of animal feed, 85 g / kg of animal feed, 90 g / kg of animal feed, 95 g / kg of animal feed, 100 g / kg of animal feed, or any amount within any of the foregoing concentration ranges.

[0097] It should be understood that the concentration of the above-mentioned azadirachtin A-rich composition is equivalent to about 0.001% w / w (weight percentage) to 10% w / w of the azadirachtin A-rich composition in the animal feed. In various aspects, the animal feed herein may contain an azadirachtin A-rich composition, which is 0.001% w / w, 0.002% w / w, 0.003% w / w, 0.004% w / w, 0.005% w / w, 0.006% w / w, 0.007% w / w, 0.008% w / w, 0.009% w / w, 0.010% w / w, 0.020% w / w, 0.030% w / w, 0.040% w / w, 0.050% w / w, 0.060% w / w, 0.070% w / w, 0.080% w / w, 0.090% w / w, 0.10% w / w, 0.11% w / w, 0.12% w / w, 0.13% w / w, 0.14% w / w, 0.15% w / w, 0.16% w / w, 0.17% w / w, 0.18% w / w, 0.19% w / w, 0.20% w / w, 0.21% w / w, 0.22% w / w, 0.23% w / w, 0.24% w / w, 0.25% w / w, 0.26% w / w, 0.27% w / w, 0.28% w / w, 0.29% w / w, 0.30% w / w, 0.31% w / w, 0.32% w / w, 0.33% w / w, 0.34% w / w, 0.35% w / w, 0.36% w / w, 0.37% w / w, 0.38% w / w, 0.39% w / w, 0.40% w / w, 0.41% w / w, 0.42% w / w, 0.43% w / w, 0.44% w / w, 0.45% w / w, 0.46% w / w, 0.47% w / w, 0.48% w / w, 0.49% w / w, 0.50% w / w, 0.51% w / w, 0.52% w / w, 0.53% w / w, 0.54% w / w, 0.55% w / w, 0.56% w / w, 0.57% w / w, 0.58% w / w, 0.59% w / w, 0.60% w / w, 0.61% w / w, 0.62% w / w, 0.63% w / w, 0.64% w / w, 0.65% w / w, 0.66% w / w, 0.67% w / w, 0.68% w / w, 0.69% w / w, 0.70% w / w, 0.71% w / w, 0.72% w / w, 0.73% w / w, 0.74% w / w, 0.75% w / w, 0.76% w / w, 0.77% w / w, 0.78% w / w, 0.79% w / w, 0.80% w / w, 0.81% w / w, 0.82% w / w, 0.83% w / w, 0.84% w / w, 0.85% w / w, 0.86% w / w, 0.87% w / w, 0.88% w / w, 0.89% w / w, 0.90% w / w, 0.91% w / w, 0.92% w / w, 0.93% w / w, 0.94% w / w, 0.95% w / w, 0.96% w / w, 0.97% w / w, 0.98% w / w, 0.99% w / w, 1.0% w / w, 2.0% w / w, 3.0% w / w, 4.0% w / w, 5.0% w / w, 6.0% w / w, 7.0% w / w, 8.0% w / w, 9.0% w / w or 10.0% w / w (i.e., the weight of the azadirachtin A-rich composition to the weight of the fish feed), or any amount within any of the foregoing ranges.

[0098] Azadirachtins may be relatively unstable in water. However, when they are components of animal feed, such as being dispersed throughout or coated on the animal feed, the azadirachtins, including azadirachtin A, are at least temporarily stable, such that they can exhibit their full biological activity during feeding. In addition, it should be noted that azadirachtin A or any neem extract agent of the present disclosure exhibits a minimal risk of toxic effects on companion animals or humans. Arthropods and other invertebrates are sensitive to the active ingredient (i.e., azadirachtin A), while higher organisms, including mammals, are not affected. In addition, since azadirachtin A or any neem extract as described herein is highly soluble in water, they do not reside and accumulate in the animal body. Instead, once the application is stopped, the pest control agent may quickly lose its effectiveness as it is metabolized, degraded, and / or excreted from the body.

[0099] The animal feed provided herein may comprise an azadirachtin A-rich composition and one or more other agents. The one or more or other agents may include ectoparasiticides, antimicrobials (e.g., antibiotics, antibacterial agents, antifungal agents, antiviral agents), antiparasitics (e.g., endoparasiticides or ectoparasiticides), or antiprotozoals. The one or more or other agents may be mixed with the animal feed, coated on the animal feed, or layered within the animal feed. The one or more or other agents may be provided separately (e.g., in liquid or solid form), and may be administered separately (e.g., before or after the animal feed) or simultaneously with the animal feed (e.g., during the animal feed).

[0100] Method for preparing animal feed

[0101] The disclosure herein provides a method for preparing an animal feed that contains one or more pest control agents, such as neem extracts containing a composition rich in azadirachtin A. The method can include the steps of providing a base feed and applying an amount of the pest control agent to the surface of the base feed. The base feed can be formed from various raw materials as described elsewhere herein. For example, the method can include coating the base feed with an amount of the pest control agent. The base feed can be at least partially coated with the pest control agent on its outer surface, or fully coated with the pest control agent on its outer surface. In some aspects, the base feed herein can contain a pest control agent that is at least partially dispersed throughout the base feed. In various aspects, the base feed herein can be at least partially coated with the pest control agent and can also have a pest control agent that is at least partially dispersed throughout the base feed. In some aspects, the pest control agent composition can be distributed throughout the base feed (such as throughout the porous matrix of the base feed). In various aspects, the base feed can be coated with more than one layer of the pest control agent on its outer surface, where each layer can contain the same pest control agent, or in some aspects, each layer can contain a different pest control agent.

[0102] The pest control agent can be incorporated into or mixed with the base feed by various methods. In various aspects, the base feed can be prepared using an extrusion process or a pressing process. The pest control agent can be mixed with the matrix during its manufacture such that it is distributed throughout all or part of the animal feed. Once the pest control agent is mixed with the base feed, the base feed and pest control agent mixture can be formed into, for example, granules, flakes, tablets, powders, or any desired form. In the case of a temperature-sensitive pest control agent, such a pest control agent can be added to the base feed after the base feed has been formed into one of the various forms shown. In various aspects, the pest control agent can be sprayed onto the base feed that has been formed into granules, flakes, tablets, etc. For example, the pest control agent can be applied as one or more layers or a top coat to the base feed. In various aspects, the pest control agent can be applied to the outer surface of the granules or flakes – in this way, the animal feed granules or flakes can become fully or partially coated with the pest control agent. One or more layers or coatings of the agent can be applied to the outer surface of the animal feed flakes or granules. Any layer or coating of the agent can be "sealed" or protected by applying one or more additional coatings or layers of a sealing substance. In various aspects, the pest control agent herein can be dispersed in one or more oils or their fractions and can be incorporated into the porous matrix within the animal feed.

[0103] For example, the medicament layer or coating can be sealed by applying a layer or coating of oil, such as animal fat. In various aspects, one or more additional animal feed layers or coatings can be applied to the (optionally sealed) animal feed coating or layer. In this way, any given animal feed flake or pellet can include multiple animal feed, sealant layer, and / or pest control agent layers. It should be understood that the animal feed described herein can be at least partially coated with a pest control agent on the outer surface. In various aspects, the animal feed herein can include a pest control agent that is at least partially dispersed throughout the animal feed. In various aspects, the animal feed herein can include a pest control agent that is at least partially coated with a pest control agent and at least partially dispersed throughout the animal feed.

[0104] Methods for incorporating a pest control agent into animal feed can include incorporating the pest control agent such that the final concentration of the pest control agent in the animal feed includes from about 0.01 grams of pest control agent per kilogram of animal feed (g / kg) to about 1000 g / kg, or about 0.01 g / kg, 0.1 g / kg, 1 g / kg, 2 g / kg, 3 g / kg, 4 g / kg, 5 g / kg, 6 g / kg, 7 g / kg, 8 g / kg, 9 g / kg or 10 g / kg, 20 g / kg, 30 g / kg, 40 g / kg, 50 g / kg, 60 g / kg, 70 g / kg, 80 g / kg, 90 g / kg, 100 g / kg, 250 g / kg, 500 g / kg or 750 g / kg, or any amount within any of the foregoing ranges. Concentrations are described in more detail herein with reference to animal feed and pest control agent compositions.

[0105] Methods for incorporating a pest control agent into animal feed can include determining the final concentration of the pest control agent incorporated as part of the animal feed. Determination of the final concentration can include sampling the animal feed using various quantitative analysis methods. For example, an animal feed sample can be extracted by the method of overnight protein precipitation in methanol. After extraction, the sample can be cleaned with Supel TM QuE Z-Sep+ (a sorbent from Sigma Aldrich, St. Louis, Missouri, USA), which is a silica-based material with an active zirconia phase, a particle size of about 50 μm, and a pore size of The resulting extraction solution can be filtered through a polytetrafluoroethylene filter with a pore size of 0.2 μm or greater. Analysis of the final concentration of the pest control agent in the animal feed sample can be performed using high performance liquid chromatography with ultraviolet detection (HPLC-UV).

[0106] The methods herein can include extracting neem extracts rich in azadirachtin A, including extracts having at least 15 wt% to 33 wt% azadirachtin A, at least 28 wt% to 31 wt% azadirachtin A, and at least 29 wt% to 30 wt% azadirachtin A.

[0107] The method can further include the step of sealing a composition rich in azadirachtin A applied to the surface of an animal feed. The composition rich in azadirachtin A can be sealed by applying a coating of oil or fat to the animal feed coated with the composition rich in azadirachtin A. Any sealing substance can be applied for sealing the composition rich in azadirachtin A such that it coats all or part of the composition rich in azadirachtin A coating.

[0108] Pest control agent composition

[0109] The present disclosure also provides a pest control agent composition for administration to companion animals, wherein the pest control agent composition can comprise one or more pest control agents. It should be understood that the pest control agent composition is not animal feed for companion animals, but is intended for administration to companion animals separately or supplementary to animal feed. The pest control agent composition can be provided separately for administration before, during, or after the administration of animal feed. Thus, in various aspects, the pest control agent composition herein can, in some aspects, be suitable for use in the form of a veterinary product or dietary supplement for reducing, preventing, or controlling pest infestation or pest infection in companion animals. The pest control agent composition can be administered to animals at the concentrations described elsewhere herein. For example, the pest control agent composition herein can be administered in an amount of from about 0.01 grams of pest control agent / kg of animal feed (g / kg) to about 100 g / kg, as described elsewhere herein. In various aspects, the pest control agent composition comprises a neem extract rich in azadirachtin A.

[0110] The pest control agent composition herein can be in any suitable form, including dry solids, semi-solids, or liquids. In various aspects, the pest control agent composition is dry solid feed. In some aspects, the pest control agent composition is semi-solid feed, wherein the semi-solid feed comprises a liquid component and a solid component. In other aspects, the pest control agent composition is liquid feed. In other aspects, the pest control agent composition can comprise both solid pest control agent composition components and liquid pest control agent composition components to be mixed at the time of feeding.

[0111] The pest control agent composition of the present invention may comprise an azadirachtin extract rich in azadirachtin A. The pest control agent composition may be in liquid, solid or semi-solid form and may also comprise one or more of excipients, diluents, carriers, vitamins, minerals or combinations thereof. In some aspects, the pest control agent composition may comprise a sweet food given to an animal at a predetermined interval. The predetermined interval may include from 1 day to 30 days. In various aspects, the predetermined interval may be more than 30 days. In various aspects, the pest control agent composition may be administered prophylactically.

[0112] The pest control agent composition may be in the form of a dietary supplement provided as any one of granules, flakes, pellets, powders, tablets, pills, capsules, cubes, chewable tablets, sweets, crumbs, pastes, gels, etc. In various aspects, the pest control agent composition of the present invention may be formed into many shapes and sizes. In various aspects, the animal feed of the present invention may be in the shape of a triangle, square, rectangle, sphere, rhombus, bone, heart, small sphere, clover, flower, fish, vegetable, star, amorphous, etc. The animal feed may be formed by a method including one or more of extrusion, distillation, cold pressing, high pressure processing, etc.

[0113] The pest control agent composition of the present invention may be comprised in one or more types of animal feed intended to be mixed with another composition such as a basal feed. The pest control agent composition may be in the form of a premix, concentrate, basal mixture, supplement, top dressing, liquid drench or combination thereof.

[0114] The pest control agent in the pest control agent composition of the present invention may comprise one or more agents for reducing, preventing or controlling an infection or infestation caused or contributed to by one or more endoparasitic or ectoparasitic pests (including any type of worm, helminth, fluke, louse, mite, tick, bacterium, virus, fungus and protozoan as described elsewhere). Each pest control agent comprised in the pest control agent composition may be individually capable of controlling one or more of parasite, bacterium, virus, fungus or protozoan infections or infestations. For example, the pest control agent composition of the present invention may comprise a pest control agent composition exhibiting one or more inhibitory effects including antiparasitic, antibacterial, antiviral, antifungal, antiprotozoal effects or any combination thereof.

[0115] The pest control agent composition can be applied before, during, or after the administration of any animal feed. In some aspects, the pest control agent composition can be co-administered with animal feed that does not contain a pest control agent. In some aspects, the pest control agent composition can be co-administered with animal feed that contains a pest control agent. When co-administered with animal feed that contains a pest control agent, the separate pest control agent composition can contain the same pest control agent as the pest control agent in the animal feed, or it can be a different pest control agent from the pest control agent in the animal feed. When co-administered with animal feed that contains a pest control agent, the concentration of the separate pest control agent composition can be the same as the concentration of the pest control agent in the animal feed, or it can be different from the concentration of the pest control agent in the animal feed. The pest control agent composition herein can be included in animal feed in the form of a veterinary product or a dietary supplement for any complete and balanced animal feed, or it can be provided as a component of a complete animal feed.

[0116] Method for applying a pest control agent

[0117] The pest control agents herein can be administered to one or more companion animals in animal feed and in pest control agent compositions. A method of managing the use of a pest control agent within animal feed can be referred to as an in-feed medicament delivery method. Accordingly, the present disclosure provides an in-feed medicament delivery method for reducing, preventing, or controlling pests. It should be understood that the in-feed medicament delivery method is not a method of topically applying a pest control agent to a target pest. The management methods herein can also utilize pest control agents in non-feed forms, such as veterinary products or dietary supplements. Accordingly, the present disclosure also provides veterinary products or dietary supplements as medicaments for reducing, preventing, or controlling pests.

[0118] A pest control agent that is not included in animal feed can be administered to an animal as a supplement to the animal feed in a separate pest control agent composition, such as in the form of a veterinary product or a dietary supplement. The animal feed can be co-administered with the pest control agent composition or separately. It should be noted that various pest control agents can be administered to sick animals, animals infested with parasites, otherwise healthy animals (to prevent parasite infection), or animals that are less aggressive due to different infections or conditions unrelated to pest infection or infestation. It should be understood that sick or less aggressive animals may eat less and thus may ingest a lower concentration of the pest control agent. Accordingly, a management method based on the use of both animal feed and a pest control agent composition can be particularly useful for managing animals whose appetite is affected by disease, infection, infestation (or less aggressive animals that generally consume less animal feed). In addition, for less aggressive or low-eating animals, the simultaneous use of a pest control agent composition and animal feed supplemented with a pest control agent can facilitate or ensure the administration of the correct concentration of the pest control agent to the animal.

[0119] The concentration of the pest control agent added to the animal feed or pest control agent composition herein can be an amount that effectively achieves the desired regulation of the behavior, development, or mortality of pests as discussed elsewhere herein. It should be understood that the precise amount of the pest control agent to be added to the animal feed or pest control agent composition can vary depending on, for example, the species of the animal, the number of animals to be fed, the degree of infestation or infection, etc. Other factors affecting the amount of the pest control agent added to the animal feed or pest control agent composition include, for example, the presence of possible competitors for the animal feed (i.e., other non-target animal species that may consume the animal feed), the type and species of the pest to be controlled, the age and maturity of the pest, the age and maturity of the animal, the season, and the aggressiveness of the animal. It should be understood that the concentration of the pest control agent added to the animal feed or pest control agent composition herein can include an amount that effectively achieves the desired effect of regulating the behavior and development of pests, where the effective amount includes one or more concentrations or concentration ranges as described herein. It should be understood that the effective amount can be determined by comparison with a control animal or group of animals not fed the pest control agent.

[0120] Animal feed and pest control agent compositions can be formulated such that the concentration of the pest control agent administered to an animal via the animal feed or pest control agent composition can include an amount effective to produce an inhibitory effect on one or more pests, the amount being in the range of from about 0.01 mg to 100 mg of pest control agent / kg body weight / day (mg / kg / day), 1 mg to 90 mg / kg / day, 1 mg to 80 mg / kg / day, 1 mg to 70 mg / kg / day, 1 mg to 60 mg / kg / day, 5 mg to 50 mg / kg / day, 10 mg to 40 mg / kg / day, 15 mg to 35 mg / kg / day, 20 mg to 30 mg / kg / day, 0.01 mg to 10 mg / kg / day or 0.01 mg to 5 mg / kg / day. It is to be understood that the range of from about 0.01 mg to 100 mg / kg / day (e.g., mg of pest control agent / kg body weight / day) includes at least 0.01 mg / kg / day, 0.02 mg / kg / day, 0.03 mg / kg / day, 0.04 mg / kg / day, 0.05 mg / kg / day, 0.06 mg / kg / day, 0.07 mg / kg / day, 0.08 mg / kg / day, 0.09 mg / kg / day, 0.10 mg / kg / day, 0.20 mg / kg / day, 0.30 mg / kg / day, 0.40 mg / kg / day, 0.50 mg / kg / day, 0.60 mg / kg / day, 0.70 mg / kg / day, 0.80 mg / kg / day, 0.90 mg / kg / day, 1.0 mg / kg / day, 2.0 mg / kg / day, 3.0 mg / kg / day, 4.0 mg / kg / day, 5.0 mg / kg / day, 6.0 mg / kg / day, 7.0 mg / kg / day, 8.0 mg / kg / day, 9.0 mg / kg / day, 10.0 mg / kg / day, 11.0 mg / kg / day, 12.0 mg / kg / day, 13.0 mg / kg / day, 14.0 mg / kg / day, 15.0 mg / kg / day, 16.0 mg / kg / day, 17.0 mg / kg / day, 18.0 mg / kg / day, 19.0 mg / kg / day, 20.0 mg / kg / day, 25.0 mg / kg / day, 30.0 mg / kg / day, 35.0 mg / kg / day, 40.0 mg / kg / day, 45.0 mg / kg / day, 50.0 mg / kg / day, 55.0 mg / kg / day, 60.0 mg / kg / day, 65.0 mg / kg / day, 70.0 mg / kg / day, 75.0 mg / kg / day, 80.0 mg / kg / day, 85.0 mg / kg / day, 90.0 mg / kg / day, 95.0 mg / kg / day or 100.0 mg / kg / day, or any amount within any of the foregoing values. Any of the above amounts effective to produce an inhibitory effect can be utilized at the concentrations administered as described herein.

[0121] The application time of the animal feed or the pest control agent composition can be determined according to the need to achieve the desired inhibitory effect. For example, the pest control agent composition or the animal feed can be applied in about 1 to 20 days or about 14 to 18 days. It should be understood that the pest control agent composition, the animal feed, or both can be continuously applied for 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, or 20 days, or any number of days falling within any of the foregoing ranges. In various aspects, the pest control agent composition or the animal feed herein can be applied for a longer period, such as more than 20 days. In various aspects, the pest control agent composition or the animal feed herein can be applied for 14 days. It should be understood that the time required to apply the pest control agent composition or the animal feed herein can have a variable length to target the developmental life stage of the pests present in the animal population, the pest control agent concentration, or any combination thereof. In some aspects, the pest control agent herein can be prophylactically applied in the diet of companion animals in an amount effective to prevent pest infection or infestation from occurring in the animals. It should also be understood that the pest control agent herein can be prophylactically applied in the diet according to the life stage or seasonally for any period of time, such as when the animal is sick.

[0122] In various management methods, the pest control agent herein can be applied discontinuously for several days, where the pest control agent is applied for a predetermined period of time and then rested for a period of time, and then applied again for a predetermined period of time and then rested for a period of time, and so on. For example, in some aspects, the pest control agent can be applied for three days every 10 days. In other aspects, the pest control agent can be applied for seven days every 14 days. The method of applying the pest control agent for a predetermined period of time and then resting for a period of time can be reused as needed, or until the pest infection or infestation is reduced, prevented, or controlled. It should be understood that the pest control agent can be applied for a predetermined period of time, including applying 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, or 10 days every 5 days to 30 days of rest between applications.

[0123] During the application period, the pest control agent composition or the animal feed can be applied multiple times a day as needed to achieve the inhibitory effect. For example, the pest control agent composition or the animal feed described herein can be applied about 1 time, 2 times, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, or more times a day. In various aspects, the pest control agent composition or the animal feed can be applied to companion animals one to three times a day. In other aspects, the pest control agent composition or the animal feed can be applied to companion animals one to two times a day.

[0124] Accordingly, the disclosure herein provides a method for reducing, preventing or controlling parasitic infections or infestations in companion animals. The method can include providing an animal feed comprising a pest control agent, the pest control agent comprising neem extract rich in azadirachtin A. The method can include administering the animal feed to one or more companion animals during an infection or infestation for 1 day to 20 days. The concentration of azadirachtin A administered to the companion animals via the animal feed is about 0.01 mg to 5 mg azadirachtin A / kg body weight / day. Various additional concentrations are provided elsewhere herein.

[0125] The disclosure also provides a method for reducing, preventing or controlling parasitic infections or infestations in companion animals, the method comprising providing a pest control agent composition comprising a pest control agent, the pest control agent comprising neem extract rich in azadirachtin A. The method can include administering the pest control agent composition to one or more companion animals during an infection or infestation for 1 day to 20 days. A concentration of azadirachtin A of about 0.01 mg to 5 mg azadirachtin A / kg body weight / day can be administered to the companion animals via the pest control agent composition. Various additional concentrations are provided elsewhere herein.

[0126] It should be understood that the definitions described herein apply to all aspects described unless otherwise stated.

[0127] In this document, unless the context clearly dictates otherwise, the terms "a", "an" or "the" are used to include one or more than one. Unless otherwise indicated, the term "or" is used to mean a non-exclusive "or". All publications, patents and patent documents cited in this document are incorporated herein by reference in their entirety as if individually incorporated by reference. If there is an inconsistency in the usage between this document and those documents incorporated by reference in this way, the usage in the incorporated reference shall be regarded as a supplement to the usage in this document; for irreconcilable inconsistencies, the usage in this document shall prevail.

[0128] Values expressed in a range format should be interpreted in a flexible manner to include not only the explicitly recited values as the limits of the range, but also all individual values or sub-ranges subsumed within that range as if each value and sub-range were explicitly recited. For example, a range of "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted to include not only about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3% and 4%) and sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the specified range. Unless otherwise indicated, the statement "about X to Y" has the same meaning as "about X to about Y". Similarly, unless otherwise indicated, the statement "about X, Y or about Z" has the same meaning as "about X, about Y or about Z".

[0129] Unless otherwise specified, ppm (parts per million), percentages, and ratios are based on weight. Percentages by weight (% w / w or w / w%) are also referred to herein as weight percentages (wt%) or weight percentages (% wt.).

[0130] Exemplary embodiments of the present invention are as follows;

[0131] Embodiment 1: A method for reducing, preventing, or controlling parasitic infections or infestations in companion animals, the method comprising:

[0132] providing an animal feed comprising a pest control agent; and

[0133] administering the animal feed to one or more companion animals during an infection or infestation for 1 day to 20 days;

[0134] wherein the pest control agent comprises neem extract rich in azadirachtin A; and

[0135] wherein the concentration of azadirachtin A administered to the companion animals through the animal feed is about 0.01 mg to 5 mg of azadirachtin A / kg body weight / day.

[0136] Embodiment 2: The method according to Embodiment 1, wherein the one or more companion animals include one or more of cats, dogs, or horses.

[0137] Embodiment 3: The method according to any one of Embodiment 1 or 2, wherein the neem extract rich in azadirachtin A comprises 15% to 33% by weight of azadirachtin A.

[0138] Embodiment 4: The method according to any one of Embodiments 1-3, wherein the parasitic infection or infestation is caused by one or more arthropod organisms.

[0139] Embodiment 5: The method according to Embodiment 4, wherein the arthropod organisms include one or more fleas, ticks, mites, worms, flies, or lice.

[0140] Embodiment 6: The method according to any one of Embodiments 1-5, wherein the parasitic infection or infestation is caused by one or more mites, the one or more mites including Dermatophagoides farinae, Dermatophagoides pteronyssinus, or Tyrophagus putrescentiae.

[0141] Embodiment 7: The method according to any one of Embodiments 1-5, wherein the parasitic infection or infestation is caused by yeast from the genus Malassezia.

[0142] Embodiment 8: The method according to any one of Embodiments 1-5, wherein the parasitic infection or infestation is caused by one or more worm species, and the one or more worm species include Dirofilaria immitis, tapeworms, hookworms, and whipworms.

[0143] Embodiment 9: The method according to any one of Embodiments 1-5, wherein the parasitic infection or infestation is caused by one or more flea species, and the one or more flea species include Ctenocephalides canis, Ctenocephalides felis, Ceratophyllus gallinae, Pulex irritans, Pulex simulans, Spilopsyllus cuniculi, and Xenopsylla cheopis.

[0144] Embodiment 10: The method according to any one of Embodiments 1-5, wherein the parasitic infection or infestation is caused by one or more louse species, and the one or more louse species include Damalinia equi, Haematopinus asini, Felicola subrostratus, Trichodectes canis, Trichodectes pilosus, and Haematomyzus setosus.

[0145] Embodiment 11: The method according to any one of Embodiments 1-5, wherein the parasitic infection or infestation is caused by one or more tick species, and the one or more tick species include Amblyomma americanum, Rhipicephalus sanguineus, Amblyomma maculatum, Dermacentor reticulatus, Dermacentor variabilis, Ixodes holocyclus, Ixodes pacificus, Ixodes ricinus, and Ixodes scapularis.

[0146] Embodiment 12: The method according to any one of Embodiments 1-11, wherein the concentration of the pest control agent is configured to produce an inhibitory effect, and the inhibitory effect includes one or more of an antiparasitic effect, an antibacterial effect, an antiviral effect, an antifungal effect, or an antiprotozoal effect.

[0147] Embodiment 13: The method according to any one of Embodiments 1-12, wherein the neem extract rich in azadirachtin A does not contain neem oil.

[0148] Embodiment 14: The method according to any one of Embodiments 1-13, wherein the animal feed further comprises one or more components selected from the group consisting of antibiotic agents, antibacterial agents, antifungal agents, antiviral agents, antiparasitic agents, or antiprotozoal agents.

[0149] Embodiment 15: The method according to any one of Embodiments 1-14, wherein the pest control agent is provided in the animal feed in an amount effective to regulate the behavior of pests.

[0150] Embodiment 16: The method according to Embodiment 15, wherein regulating the behavior of the pests includes one or more of the following: a change in feeding habits, a change in feeding patterns, a change in appetite, a change in movement patterns, a change in mating patterns, a change in development, or a change in fertility, as compared to pests found on control animals not fed the pest control agent.

[0151] Embodiment 17: The method according to embodiment 16, wherein the change in the feeding pattern includes a reduction in the feeding pattern.

[0152] Embodiment 18: The method according to embodiment 16, wherein the change in the appetite includes a decrease in the appetite.

[0153] Embodiment 19: The method according to embodiment 16, wherein the change in the movement includes a reduction in the movement.

[0154] Embodiment 20: The method according to embodiment 16, wherein the change in the mating pattern includes a reduction in the mating pattern.

[0155] Embodiment 21: The method according to embodiment 16, wherein the change in the development includes an inhibition of the development.

[0156] Embodiment 22: The method according to embodiment 16, wherein the change in the fertility includes an inhibition or delay of egg laying, an inability to produce viable eggs, or a reduction in the total number of pregnant female pests.

[0157] Embodiment 23: The method according to any one of embodiments 1-22, wherein the pest control agent is provided in the animal feed in an amount effective to regulate pests by reducing the number of live pests present on the animal or in the animal's habitat as compared to the pests found on control animals not fed the pest control agent.

[0158] Embodiment 24: A method for reducing, preventing or controlling parasite infection or infestation in companion animals, the method comprising:

[0159] providing a pest control agent composition comprising an Azadirachta indica extract rich in azadirachtin A; and

[0160] administering the pest control agent composition to one or more companion animals during the period of infection or infestation for 1 day to 20 days;

[0161] wherein the concentration of azadirachtin A administered to the companion animals through the pest control agent composition is from about 0.01 mg to 5 mg of azadirachtin A / kg body weight / day.

[0162] Embodiment 25: The method according to embodiment 24, wherein the pest control agent composition comprises a veterinary medicine product.

[0163] Embodiment 26: The method according to embodiment 24, wherein the pest control agent composition comprises a dietary supplement.

[0164] Embodiment 27: The method according to any one of embodiments 24-26, wherein applying the pest control agent comprises applying the pest control agent once to three times a day.

[0165] Embodiment 28: The method according to any one of embodiments 24-27, wherein the pest control agent composition is applied to the animal for 14 days.

[0166] Embodiment 29: The method according to any one of embodiments 24-28, wherein the one or more companion animals comprise one or more of cats, dogs or horses.

[0167] Embodiment 30: The method according to any one of embodiments 24-29, wherein the neem extract rich in azadirachtin A comprises 15% to 33% by weight of azadirachtin A.

[0168] Embodiment 31: A neem extract rich in azadirachtin A, the neem extract being used to reduce, prevent or control parasitic infections or infestations in companion animals by following steps comprising:

[0169] providing an animal feed comprising a pest control agent; and

[0170] during an infection or infestation, applying the animal feed to one or more companion animals for 1 day to 20 days;

[0171] wherein the pest control agent comprises a neem extract rich in azadirachtin A; and

[0172] wherein the concentration of azadirachtin A applied to the companion animal through the animal feed is about 0.01 mg to 5 mg of azadirachtin A / kg body weight / day.

Claims

1. A method for reducing, preventing or controlling parasitic infections or infestations in companion animals, the method comprising: Providing animal feed containing a pest control agent; and During an infection or infestation, administering the animal feed to one or more companion animals for 1 day to 20 days; wherein the pest control agent contains neem extract rich in azadirachtin A; and wherein the concentration of azadirachtin A administered to the companion animal through the animal feed is about 0.01 mg to 5 mg of azadirachtin A / kg body weight / day.

2. The method according to claim 1, wherein the one or more companion animals include one or more of cats, dogs or horses.

3. The method according to any one of claims 1 or 2, wherein the neem extract rich in azadirachtin A contains 15% to 33% by weight of azadirachtin A.

4. The method according to any one of claims 1 - 3, wherein the parasitic infection or infestation is caused by one or more arthropod organisms, the one or more arthropod organisms including one or more fleas, ticks, mites, worms, flies or lice.

5. The method according to any one of claims 1 - 4, wherein: The parasitic infection or infestation is caused by one or more mites, including Dermatophagoides farinae, Dermatophagoides pteronyssinus or Tyrophagus putrescentiae; or wherein the parasitic infection or infestation is caused by yeast from the genus Malassezia; or wherein the parasitic infection or infestation is caused by one or more worm species, including Dirofilaria immitis, tapeworms, hookworms and whipworms; or wherein the parasitic infection or infestation is caused by one or more flea species, including Ctenocephalides canis, Ctenocephalides felis, Ceratophyllus gallinae, Pulex irritans, Pulex simulans, Spilopsyllus cuniculi and Xenopsylla cheopis; or wherein the parasitic infection or infestation is caused by one or more louse species, including Damalinia equi, Haematopinus asini, Felicola subrostratus, Trichodectes canis, Trichodectes canis and Haematomyzus setosus; or wherein the parasitic infection or infestation is caused by one or more tick species, including Amblyomma americanum, Rhipicephalus sanguineus, Amblyomma maculatum, Dermacentor reticulatus, Dermacentor variabilis, Ixodes holocyclus, Ixodes pacificus, Ixodes ricinus and Ixodes scapularis.

6. The method according to any one of claims 1 - 5, wherein the concentration of the pest control agent is configured to produce an inhibitory effect, the inhibitory effect including one or more of an anti - parasitic effect, an antibacterial effect, an antiviral effect, an antifungal effect or an antiprotozoal effect.

7. The method according to any one of claims 1 - 6, wherein the pest control agent is provided in the animal feed in an amount effective to modulate the behavior of the pest.

8. The method according to claim 7, wherein modulating the behavior of the pest includes one or more of the following: a change in feeding habits, a change in feeding patterns, a change in appetite, a change in movement patterns, a change in mating patterns, a change in development or a change in fertility, compared to pests found on control animals not fed the pest control agent.

9. The method according to claim 8, wherein the change in feeding patterns includes a reduction in feeding patterns.

10. The method according to claim 8, wherein the change in appetite includes a decrease in appetite.

11. The method according to claim 8, wherein the change in movement includes a decrease in movement.

12. The method according to claim 8, wherein the change in mating pattern includes a decrease in mating pattern.

13. The method according to claim 8, wherein the change in development includes an inhibition of development.

14. The method according to claim 8, wherein the change in fertility includes an inhibition or delay in egg laying, an inability to produce viable eggs, or a decrease in the total number of pregnant female pests.

15. An Azadirachta indica extract rich in azadirachtin A, the Azadirachta indica extract being used to reduce, prevent, or control parasitic infections or infestations in companion animals by following steps including: Providing an animal feed comprising a pest control agent; and Administering the animal feed to one or more companion animals during an infection or infestation for 1 day to 20 days; wherein the pest control agent comprises an Azadirachta indica extract rich in azadirachtin A; and wherein the concentration of azadirachtin A administered to the companion animals through the animal feed is about 0.01 mg to 5 mg of azadirachtin A / kg body weight / day.

16. A method for reducing, preventing, or controlling parasitic infections or infestations in companion animals, the method comprising: Providing animal feed containing a pest control agent; and During an infection or infestation, administering the animal feed to one or more companion animals for 1 day to 20 days; wherein the pest control agent contains neem extract rich in azadirachtin A; and wherein the concentration of azadirachtin A administered to the companion animal through the animal feed is about 0.01 mg to 5 mg of azadirachtin A / kg body weight / day.

17. The method according to claim 16, wherein the one or more companion animals include one or more of cats, dogs, or horses.

18. The method according to claim 16, wherein the Azadirachta indica extract rich in azadirachtin A comprises 15 wt% to 33 wt% of azadirachtin A.

19. The method according to claim 16, wherein the parasitic infection or infestation is caused by one or more arthropod organisms.

20. The method according to claim 19, wherein the arthropod organisms include one or more fleas, ticks, mites, worms, flies, or lice.

21. The method according to claim 16, wherein the parasitic infection or infestation is caused by one or more mites, the one or more mites including Dermatophagoides farinae, Dermatophagoides pteronyssinus, or Tyrophagus putrescentiae; or wherein the parasitic infection or infestation is caused by yeast from the genus Malassezia; or wherein the parasitic infection or infestation is caused by one or more worm species, the one or more worm species including Dirofilaria immitis, tapeworms, hookworms, and Trichuris vulpis; or wherein the parasitic infection or infestation is caused by one or more flea species, the one or more flea species including Ctenocephalides canis, Ctenocephalides felis, Ceratophyllus gallinae, Pulex irritans, Pulex simulans, Spilopsyllus cuniculi, and Xenopsylla cheopis; or wherein the parasitic infection or infestation is caused by one or more louse species, the one or more louse species including Damalinia equi, Haematopinus asini, Felicola subrostratus, Trichodectes canis, Trichodectes pilosus, and Haemadipsa setifera; or wherein the parasitic infection or infestation is caused by one or more tick species, the one or more tick species including Amblyomma americanum, Rhipicephalus sanguineus, Amblyomma maculatum, Dermacentor reticulatus, Dermacentor variabilis, Ixodes holocyclus, Ixodes pacificus, Ixodes ricinus, and Ixodes scapularis.

22. The method according to claim 16, wherein the concentration of the pest control agent is configured to produce an inhibitory effect, the inhibitory effect including one or more of an anti - parasitic effect, an antibacterial effect, an antiviral effect, an antifungal effect, or an antiprotozoal effect.

23. The method according to claim 16, wherein the neem extract rich in azadirachtin A does not contain neem oil.

24. The method according to claim 16, wherein the animal feed further comprises one or more components selected from the group consisting of: antibiotic agents, antibacterial agents, antifungal agents, antiviral agents, antiparasitic agents, or antiprotozoal agents.

25. The method according to claim 16, wherein the pest control agent is provided in the animal feed in an amount effective to modulate the behavior of the pest.

26. The method according to 25, wherein modulating the behavior of the pest comprises one or more of the following: a change in feeding habits, a change in feeding patterns, a change in appetite, a change in movement patterns, a change in mating patterns, a change in development, or a change in fertility, compared to pests found on control animals not fed the pest control agent.

27. The method according to claim 16, wherein the pest control agent is provided in the animal feed in an amount effective to modulate the pest by reducing the number of live pests present on the animal or in the animal's habitat compared to pests found on control animals not fed the pest control agent.

28. A method for reducing, preventing, or controlling parasitic infection or infestation in companion animals, the method comprising: Providing a pest control agent composition containing neem extract rich in azadirachtin A; and During an infection or infestation, administering the pest control agent composition to one or more companion animals for 1 day to 20 days; wherein the concentration of azadirachtin A administered to the companion animal through the pest control agent composition is about 0.01 mg to 5 mg of azadirachtin A / kg body weight / day.

29. The method according to claim 28, wherein the pest control agent composition comprises a veterinary product.

30. The method according to claim 28, wherein the pest control agent composition comprises a dietary supplement.

31. The method according to claim 28, wherein applying the pest control agent comprises applying the pest control agent once to three times per day.

32. The method according to claim 28, wherein the pest control agent composition is applied to the animal for 14 days.

33. The method according to claim 28, wherein the one or more companion animals comprise one or more of a cat, a dog, or a horse.

34. The method according to claim 28, wherein the neem extract rich in azadirachtin A comprises 15% to 33% by weight of azadirachtin A.

35. A neem extract rich in azadirachtin A for reducing, preventing, or controlling parasitic infections or infestations in companion animals by following steps comprising: providing animal feed comprising a pest control agent; and during an infection or infestation, applying the animal feed to one or more companion animals for 1 day to 20 days; wherein the pest control agent comprises a neem extract rich in azadirachtin A; and wherein the concentration of azadirachtin A applied to the companion animal via the animal feed is from about 0.01 mg to 5 mg of azadirachtin A / kg body weight / day.

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