JP5791776B1 - Topical liquid insecticide composition - Google Patents

Abstract

Disclosed is a topical liquid formulation for treating fleas and ticks in domestic animals. A composition comprising an ether pyrethroid such as etofenprox and a neonicotinoid such as nitenpyram that is soluble in an aprotic polar solvent. Furthermore, a composition comprising an insect growth regulator such as pyriproxyfen. The total concentration of the hydrophobic active ingredient and the hydrophilic active ingredient can exceed 60 weight percent. [Effect] The insecticide composition is safe and effective for both feline and canine animals, unlike a flea treatment agent that is generally available, and a single topical application is effective for at least several weeks. It can be. [Selection figure] None

Description

  The present invention relates generally to insecticides, and more specifically to insecticidal formulations for use in domestic animals such as cats and dogs.

  As the number of dog and cat owners increases, the medical and health services available to address the needs of sick and elderly pets, and to maintain young and healthy animals, have surged. Yes. Veterinarians, as a routine task, examine pets for signs of disease and infection, including the presence of parasites or various types of cancer. Cats are particularly prone to feline leukemia and may develop diabetes.

  Many diseases that affect the health of both cats and dogs are caused by ticks and fleas that act as viral and parasite mediators through bites that can spread blood-borne infections. The market for flea and tick products in the United States is approximately $ 552 million, with approximately nine companies controlling the market. Growth between 2007 and 2012 was 0.6%, but for pet owners, especially those who are willing to consider pets as a family member and spend money for their pet's health and well-being. Due to the increasing number, the market is expected to expand over the next five years.

  There are several disadvantages to the flea / tick products currently used for dogs and cats. Ideally, to address one or more of the flaws of currently available flea / tick formulations, the product should have: (1) Applies to small dogs or cats High concentration of active ingredient to minimize the amount of topical required for (2) stable and effective so that flea killing continues for at least 30 days after application A liquid formulation; (3) a consumer-safe product in case of skin contact; (4) a formulation that is stable at ambient, low and high temperatures and has a suitable shelf life for commercial use; 5) Products that are non-toxic to dogs or cats when ingested; and (6) Products that are ideally equally safe and effective for use in both dogs and cats.

  Many of the available flea / tick topical compositions are not safe and effective for use with both dogs and cats, which are two major domestic pets. Another disadvantage of currently used products is that a more effective high concentration of active ingredient is not available in a stable liquid form.

  Effective topical “spot-on” coatings are a commercially desirable feature, especially when the formulation can be applied based on body weight rather than on animal species. Some of the liquid spot products for dogs cannot be used for cats.

  Patent Document 1 describes an insecticide formulation consisting of pyriproxyfen dissolved in alcohol and up to 25% by weight of dinotefuran, which is described as applicable for use in both dogs and cats . In Patent Document 2, a topical preparation for killing endoparasites and ectoparasites combines a macrocyclic lactone and a neonicotinoid in addition to permethrin and an insect growth regulator. The first two ingredients are packaged separately to prevent interaction with permethrin and cannot be supplied as a stable liquid.

Estimated populations of felines and canines The number of domestic pets in the United States has reached millions, with cats and dogs making an overwhelming contribution. The number of cats in the United States in 2012 was estimated to exceed 74 million. The United States count does not include wild and local cat populations, which are considered to be about 50 million. 30-40% of households in the United States have one or more cats or dogs. The average annual veterinary spending per household is $ 378, comparable to that used for horses for dogs, while the average cost for cats is $ 191. (2012 US Pet Ownership & Demographics Sourcebook).

  Table 1 shows the estimated number of cats and dogs in the top 10 countries with the highest number of individuals.

  The number of canines and felines is highest in the United States. However, in the UK and Germany, cats are more popular as pets than dogs.

  Dogs and cats are big businesses in the United States. The development and expansion of dog food and cat food continues to evolve, and specialty brands and organic feeds enjoy a profitable niche market. New breeds of dogs and cats are emerging, there are so-called designer breeds such as Labradoodle and Cockapoo, and other purebred dogs are recognized by organizations such as American Kennel Club.

  Consumers are also becoming familiar with cat breeds, including ancient breeds, domestic cat hybrids, and domestic / wild cat hybrids. There is a difference in breed classification among the cat registries. At least 55 different varieties are recognized, but a vast number of cats are mixed races. Recognized varieties include natural, hybrid and mutant species.

  The list of recognized cat breeds is long and includes the following: Abyssinian, Aegean, Australian Mist, American Curl, American Bobtail, American Polydactyl, American shorthair, American Wirehair, Arabian Man, Asian, Asian Semi-longhair, Balinese , Bambino, Bengal, Birman, Bombay, Brazilian Shorthair, British Shorthair, British Longhair, Burmese, Vermira (Burmilla), California Spangled Cat (California Spangled) Cat, Chantilly / Tiffany, Chartreux, Clausie, Cheetoh, Colorpoint Shorthair, Cornish Rex, Kimlic, Cyprus Cat (Cyprus cat), Devon Rex (Doinskoy), Dragon Li (Dragon Li), Dwelf (Dwelf), Egyptian Mau (European Shorthair), Exotic Shorthair (Exotic) Shorthair, German Rex, Havana Brown, Highlander, Himalayan / Colorpoint Persian, Japanese Bobtail, Javanese, Khao Manee Manee, Korat, Kurilian Bobtail, La Perm (LaPerm), Maine Coon, Manx, Mekong bobtail, Minskin, Munchkin, Nebelung, Napoleon, Norwegian Forest Cat (Norwegian) Forest Cat, Ocicat, Ojos Azules, Oregon Rex, Oriental Bicolor, Oriental Shorthair, Oriental Longhair, Persian ( Persian), Peterbald, Pixie-bob, Ragamuffin, Ragdoll, Russian Blue, Russian Black, White or Tabby, Savannah, Scottish Fold, Selkirk Rex, Serengete Serengeti cat, Serrade petit, Siamese, Siberian Singapura, Snowshoe, Sokoke, Somali, Sphynx, Swedish forest cat (Swedish) forest cat, Thailand, Tonkinese, Toyger, Turkish Angora, Turkish Van, Ukrainian Levkoy, and York Chocolate Cat (York) Chocolate Cat).

  The list of varieties recognized by the American Kennel Club includes Affenpinscher, afghan hound, Airedale Terrier, Akita, Alaskan Malamute, American English Coon Hound (American English Coonhound), American Eskimo Dog (American Eskimo Dog), American Foxhound (American Foxhound), American Staffordshire Terrier, American Water Spaniel, Anatolian Shepherd Dog Dog, Australian Cattle Dog, Australian Shepherd, Australian Terrier, Basenji, Basset Hound, Beagle ), Bearded Collie, Beauceron, Bedlington Terrier, Belgian Malinois, Belgian Sheepdog, Belgian Tervuren, Bernese Mountain dog ), Bichon Frize, Black and Tan Coonhound, Black Russian Terrier, Bloodhound, Bluetick Coonhound, Border Collie ), Border Terrier, Borzoi, Boston Terrier, Bouview des Flandres, Boxer, Boykin Spaniel, Briard, Brittany ), Brussels Griffon Bull Terrier, Bulldog, Bullmastiff, Cairn Terrier, Canaan dog, Cane Corso, Cardigan Welsh Corgi, Cavalier King Charles Spaniel King Charles Spaniel, Cesky Terrier, Chesapeake Bay Retriever, Chihuahua, Chinese Crested, Chinese Shar-Pei, Chow Chow, Cirnekodel Etna (Cirneco dell'Etna), Clumber Spaniel, Cocker Spaniel, Collie, Curly-Coated Retriever, Dachshund, Dalmatian, Dandy Dinmont Dermont Terrier , Doberman Pinscher, Dogue de Bordeaux, English Cocker Spaniel, English Foxhound, English Setter, English Springer Spaniel English Toy Spaniel, Entlebucher Mountain Dog, Field Spaniel, Finish Lapphund, Finish Spitz, Flat-Coated Retriever Retriever), French bulldog, German Pinscher, German Shepherd Dog, German Shorthaired Pointer, German -German Wirehaired Pointer, Giant Schnauzer, Glen of Imaal Terrier, Golden Retriever, Gordon Setter, Great Dane Great Pyrenees, Greater Swiss Mountain Dog, Greyhound, Harrier, Havanese, Ibizian Hound, Icelandic Sheepdog Irish Red and White Setter, Irish Setter, Irish Terrier, Irish Water Spaniel, Irish Wolfhound, Italian Greyhound (Ital ian Greyhound), Japanese Chin, Keeshond, Kerry Blue Terrier, Common Doll (Komondor), Kuvasz, Labrador Retriever (Lakeland Terrier) , Leonberger, Lhasa Apso, Lowchen, Maltese, Manchester Terrier, Mastiff, Miniature Bull Terrier, Miniature Pinscher, Miniature Schnauzer, Neapolitan Mastiff, Newfoundland, Norfolk Terrier, Norwegian Buhund, Norwegian Elkhound, Norwegian Lund (Norwegian Lundehund) Norwich Terrier, Nova Scotia Duk Tolling Retriever, Old English Sheepdog, Otterhound, Papillion, Parson Russell Terrier, Pekingese ( Pekingese, Pembroke Welsh Corgi, Petit Basser Griffon Vendeen, Pharaoh Hound, Plott, Pointer, Polish Lowland Sheepdog, Pomeranian, Poodle, Portuguese Water Dog, Pug, Puli, Pyrencan Shepherd, Rat Terrier, Redbone Coonhound (Redbone Coonhound), -Rhodesian Ridgeback, Rottweiler, Russsell Terrier, Saint Bernard, Saluki, Samoyed, Schipperke, Scottish Deerhound (Scottish) Deerhound, Scottish Terrier, Sealyham Terrier, Shetland Sheepdog, Shiba Inu, Shih Tzu, Siberian Husky, Silky Terrier , Skye Terrier, Smooth Fox Terrier, Soft Coated Wheaten Terrier, Spinone Italiano, Staffordshire Bull Terrier, Standard Schnauzer ), Sussex Nissel (Sussex Spaniel), Swedish Vallhund, Tibetan Mastiff, Tibetan Spaniel, Tibetan Terrier, Toy Fox Terrier, Treeing Walker Coon Hound (Treeing Walker Coonhound), Vizsla, Weimaraner, Welsh Springer Spaniel, Welsh Terrier, West Highland White Terrier, Whippet, Wire Includes Fox Fox Terrier, Wirehaired Pointing Griffon, Xoloitzcuintli, and Yorkshire Terrier.

Flea and Tick Control Products There are a number of flea and tick control products currently available for use in controlling fleas and ticks in felines. Products from major manufacturers are marketed as monthly topical preparations, most as “spot-on” coatings on animal skin. Both are supposed to kill flea adults and most kill mites, but the majority do not kill flea eggs. Products containing fipronil kill lice, but none of these products claim to keep flies away.

  Most main line manufacturers of flea / tick products use varying concentrations of fipronil, dinotefuran, imidacloprid, or etofenprox in combination with pyriproxyfen or (S) methoprene. There are few botanicals that appear to be effective, except for a mixture of natural vegetable oils sold by Sergeant's that are described as having efficacy against adult fleas, ticks, and lice against products containing fipronil. Table 2 lists the active ingredients of several popular commercial products that are typically supplied as topical therapeutics.

U.S. Patent No. 6,867,223 U.S. Patent No. 7,368,435

  The present invention relates to new liquid formulations containing high concentrations of hydrophilic and hydrophobic insecticides, and in particular to compositions comprising dinotefuran, etofenprox, and pyriproxyfen as active components. Dinotefuran is a neonicotinoid compound that is water soluble, whereas etofenprox is essentially water insoluble. Other water-soluble neonicotinoids such as nitenpyram can be used, but most neonicotinoids are relatively insoluble in aprotic polar solvents and are sufficient to form stable solutions containing hydrophobic components. Does not dissolve. In the most preferred formulation, the hydrophobic component is ether pyrethrin etofenprox, which can be prepared with dinotefuran and pyriproxyfen in a weight percent range of 40-60% in an aprotic polar solvent. The weight percent of the solvent or mixed solvent is less than 35%. The active hydrophilic and hydrophobic components form a stable solution with a shelf life of at least several months.

  There are a number of solvents and solvent combinations that can be used to solubilize mixtures of hydrophilic and hydrophobic active ingredients in the disclosed liquid formulations. Such solvents include N-methylpyrrolidone (NMP), propylene carbonate, ethyl acetate, tetrahydrofurfuryl alcohol (THFFA), glycofurol, glycerol formal, solketal (alone or in combination with DMSO), 4-hydroxy- 1,3-dioxane, 1,2-glycerol-formal, and N-octylpyrrolidone are included. A preferred solvent is N-octylpyrrolidone, which may be combined with NMP or propylene carbonate.

  The present invention is particularly useful for the local treatment of flea eggs, flea larvae, ticks, mite eggs, tick nymphs, mites, and mosquitoes in cats and canines, as well as ticks and fleas A combination of active ingredients (“actives”) is provided.

  A particularly surprising aspect of the disclosed formulations is the high concentration of hydrophilic and hydrophobic actives that can be solubilized in aprotic polar liquids. Dinotefuran is hydrophilic and readily soluble in water, whereas etofenprox is hydrophobic and essentially insoluble in water. Combinations of dinotefuran and up to 40-60 wt% etofenprox can be realized in aprotic polar solvents. Liquid formulations containing high concentrations of ether pyrethroids such as etofenprox are extremely effective in combating fleas and ticks and are non-toxic when used as topical agents. Products that use permethrin instead of etofenprox are toxic and cannot be used in felines. The disclosed formulations containing high concentrations of etofenprox can be used effectively and safely in canines and felines, and other mammals such as rabbits, mice, rats, and guinea pigs.

  Preferably, the topical solution comprises N-octylpyrrolidone or a mixture of dinotefuran, etofenprox, and pyriproxyfen formulated in a mixture of N-octylpyrrolidone and NMP. Pyriproxyfen is an insect growth regulator that is present at 0.4 to 0.5 weight percent. In a typical preferred combination, dinotefuran is 4.95 weight percent and etofenprox is 60 weight in a mixed solvent of 34.6 weight percent N-octylpyrrolidone or 28.61 weight percent NMP and 6.00 weight percent N-octylpyrrolidone. Percent, and pyriproxyfen is 0.44 weight percent. This solution provides greater than 65 weight percent active ingredient and is effective as a spot-on formulation for combating and killing fleas and ticks in cats and dogs.

More specifically, the present invention provides the following:
[1] A composition comprising a hydrophilic component neonicotinoid and a hydrophobic component pyrethroid or ether pyrethroid that is soluble in an aprotic polar solvent, providing a solution comprising 40 to 65 weight percent ether pyrethroid;
[2] The composition according to [1], further comprising an insect growth regulator;
[3] The composition of [2], further comprising 0.2 to 0.3 weight percent synergist to enhance pyrethroid activity, wherein the synergist is selected from piperonyl butoxide or n-octylbicycloheptene dicarboximide. A composition of;
[4] The hydrophobic component and the hydrophilic component according to [1], which are any of pharmaceutically acceptable salts, enantiomers, racemates, prodrugs, derivatives, or metabolites thereof. Composition;
[5] The composition according to [1], wherein the neonicotinoid is acetamiprid, clothianidin, imidacloprid, nitenpyram, sulfoxafurol, thiacloprid, thiamethoxam, or dinotefuran;
[6] pyrethroid or ether pyrethroid is etofenprox, alletrin, bifenthrin, cyfluthrin, cypermethrin, ciphenothrin, deltamethrin, esfenvalerate, fenpropatoline, fenvalerate, flucitrinate, flumethrin, imiprotolin, λ-cyhalothrin, The composition according to [1], which is metfurthrin, praretrin, resmethrin, silafluophene, sumitrine, tau-fluvalinate, tefluthrin, tetramethrin, tralomethrin, and transfluthrin;
[7] The composition according to [2], wherein the insect growth regulator is pyriproxyfen, metoprene, or phenoxycarb;
[8] The composition of [2], wherein the weight percent of neonicotinoid, pyrethroid, and insect growth regulator comprises 40-65 weight percent in an aprotic polar solvent;
[9] The aprotic polar solvent according to [1], wherein the aprotic polar solvent is selected from one or more of N-octylpyrrolidone, N-methylpyrrolidone, tetrahydrofurfuryl alcohol, propylene carbonate, and ethyl acetate. Composition;
[10] The composition according to [1], wherein the weight percentage of etofenprox is 40 to 60% by weight;
[11] The composition according to [6], wherein the weight percent of dinotefuran is 4 to 6% by weight;
[12] The composition according to [7], wherein the weight percentage of pyriproxyfen is 0.3 to 0.5% by weight;
[13] A method for topically treating fleas and ticks in fur animals comprising the step of topically administering an effective amount of the composition according to [8];
[14] The method according to [13], wherein a small amount is locally administered to a cat or dog;
[15] The method according to [14], wherein the amount is 1 to 8 ml;
[16] The method according to [15], wherein the amount is periodically administered every 30 to 60 days;
[17] 40-60 weight percent etofenprox in an aprotic polar solvent selected from N-methylpyrrolidone, N-octylpyrrolidone, propylene carbonate, tetrahydrofurfuryl alcohol, ethyl lactate, or mixtures thereof, 4 to A kit for treating fleas and ticks in an animal comprising a solution of 5 weight percent dinotefuran and optionally 0.3-0.5 weight percent pyriproxyfen;
[18] The kit of [17], further comprising 0.3 to 0.5 weight percent pyriproxyfen;
[19] The kit of [18], further comprising 0.1 to 0.2 weight percent piperonyl butoxide or n-octylbicycloheptene dicarboximide; and
[20] The kit according to [17], comprising an individually containerized solution in an amount selected from 0.5 to 8 ml for spot treatment of a cat or dog.

DESCRIPTION OF THE EMBODIMENTS Detailed Description of the Invention There are a number of products available to dogs that act to kill or prevent fleas and ticks. A well-known topical spot treatment for dogs is a product containing fipronil, ciphenothrin, and (S) -methoprene. The active ingredient in the 45-88 lbs. Canine composition ranges from about 22.8% by weight. The ingredients in Squeeze-On® for dogs are ciphenothrin and fipronil. This combination of actives is described as killing fleas, flea eggs, flea larvae, and ticks. These flea / tick formulations cannot be used in cats.

  A typical flea treatment for cats is FRONTLINE® Feline, which is marketed with only two active ingredients (fipronil and S-methoprene). The latter is an insect growth regulator. The active ingredient accounts for only about 12% and the inactive ingredient accounts for over 78% of the formulation. In comparison, the flea / tick formulation described herein has a much higher concentration of active ingredient and is therefore more effective and durable.

  Table 3 illustrates topical formulations illustrating the present invention, preferably comprising dinotefuran, pyriproxyfen, and etofenprox. Dinotefuran is a member of the neonicotinoid class of insecticides, and etofenprox is an ether pyrethroid. Most pyrethroids are esters. Pyriproxyfen is an insect growth regulator. Dinotefuran kills fleas but not mites, and etofenprox kills both fleas and ticks. Dinotefuran provides a “speed of kill” that etofenprox does not provide. Table 3 shows formulations containing dinotefuran, etofenprox, and pyriproxyfen that can be applied to animals as a topical “spot-on”. These formulations are particularly effective for use as topical coatings in canines and felines to kill fleas, ticks, and flea eggs.

  Dinotefuran is a hydrophilic compound that dissolves in water (about 40 g / L). As shown in Table 4, with the exception of a few, other neonicotinoids have poor solubility. Although dinotefuran is most preferred, nitenpyram is highly hydrophilic and can be used in formulations where higher levels of neonicotinoids may be desirable. The ether pyrethroid etofenprox dissolves in some aprotic polar solvents and constitutes up to 40-60 weight percent, but most ether pyrethroids only dissolve very little. Other ether pyrethroids may be useful if they have insecticidal activity and may be desirable due to cost and relatively low hydrophobicity.

  The described formulations are stable at temperatures from 0 ° F. to at least 120 ° F. 1 month at test temperatures of 0 ° F, 32 ° F, 70 ° F, and 120 ° F. Table 5 shows the results for several formulations stored at temperatures ranging from freezing to 50 ° F. No precipitation or crystallization was observed.

  Etofenprox is a hydrophobic compound that is relatively insoluble in water [1 mg / L]. Both dinotefuran and etofenprox are soluble in pyrrolidone compounds. N-octylpyrrolidone is a preferred solvent that can be used alone or mixed with other aprotic polar liquids. Other solvent systems are suitable and are listed in Table 2.

  New formulations are made for use in both canines and felines. Etofenprox is not toxic to felines, unlike other members of the pyrethroid class of insecticides. Most products available for dogs contain pyrethroid esters that are toxic to felines, and therefore cannot be used for cats. Formulations containing high levels of the ether pyrethroid etofenprox can be used in rabbits, mouse rats, hamsters, and other mammals including guinea pigs.

  An important and unexpected aspect of the present invention is the high concentration (about 45-65%) of the total amount of pesticide active substance in solution that is stable over time at ambient and low temperatures. This is particularly unexpected since etofenprox is relatively insoluble in solvents that dissolve hydrophilic substances. The hydrophilic active substance and hydrophobic active substance in the described mixture form a stable solution with good temperature stability. Although dinotefuran at a concentration of 5% can crystallize from many hydrophilic solvents at 0 ° F and 32 ° F, in liquid formulations containing 40-60 weight percent etofenprox and up to 5% dinotefuran, the precipitate also crystallizes. Neither was observed. Even with this high concentration of active ingredient, these solutions are stable for 1 month at test temperatures of 0 ° F, 32 ° F, 70 ° F, and 120 ° F.

Flea Disease A catastrophic disease in cats is cytoxonosis, a blood parasite commonly present from central Kansas to the south and east around Jacksonville, Florida. There is no effective treatment for cytokes zone disease.

  The most common problem with fleas in both cats and dogs is flea allergic dermatitis. The flea injects saliva into the skin while eating, which causes the animal to feel itchy where the salivary protein is deposited at the bite site. Subsequent scratching behavior can cause significant hair loss at the bite site.

  Fleas can cause allergic reactions in both pets and humans. Flea bites in cats or dogs can lead to urticaria or rashes, which can cause severe skin infections, such as cat miliary dermatitis. Humans are often stung by fleas that have migrated from infested animals, resulting in itching, redness, and varying degrees of dermatitis.

  Anemia is a very serious condition that can occur as a result of fleas feeding on red blood cells in severe flea infestations. This condition is particularly severe in kittens and puppies, where red blood cell loss affects the ability to efficiently carry oxygen to the brain. Even after treatment of anemia, animals may suffer permanent brain damage.

  Tape Worms are carried in the flea's body and are transmitted to cats and dogs when animals lick or bite flea bites. Ingested tapeworms can breed in the digestive system and grow to a length of several feet. Infected dogs or cats, especially young ones, cannot grow up robustly and are usually underweight.

  The plague is a disease that affects humans even today. The disease is transmitted to humans through flea bites, most often to the flea infestation site of pet owners. Typically, fleas are brought into the home by pets that may or may not show evidence of fleas.

  The most common rash fever in the southern states is caused by fleas from both wild animals and pets such as cats or dogs. Typical symptoms of rash fever include back pain, abdominal pain, headache, nausea, vomiting, and red rash. The worst symptom of this condition is the extremely high fever (105-106 degrees) caused by this condition, which may last for several weeks.

Tick diseases in pets There are several diseases that can be transmitted from tick bites to pets. The most common tick-borne diseases seen in the United States are Lyme disease, Rocky mountain spotted fever, Ehrlicia, and tick paralysis. Some of these and especially other tick-borne diseases that affect dogs and cats are listed below.

  Lyme disease, also called borreliosis, is caused by the bacterium Borrelia burgdorferi. Deer mites carry these bacteria and propagate them to the animal while sucking the animal's blood. In order for bacteria to be delivered to the animal's bloodstream, mites need to attach to the dog (or cat) for about 48 hours. Transmission usually does not occur if ticks are removed within one or two days.

  Common signs of Lyme disease include lameness, fever, lymph node and joint swelling, and decreased appetite. In severe cases, animals may develop kidney disease, heart condition, or nervous system disorders. Animals do not develop a “Lyme disease rash” that is commonly seen in humans suffering from Lyme disease.

  Blood tests are needed to diagnose pet Lyme disease. If the test is positive, oral antibiotics are usually prescribed. Dogs that have recovered from Lyme disease because they are not immunized can again suffer from this disease. The Lyme disease vaccine can be used in dogs, but unfortunately, this vaccine cannot be used in cats.

  A common disease found in dogs in the eastern, midwestern, and plain regions of the United States is Rocky Mountain spotted fever. Cats can be infected with RMSF, but the incidence of cats is much lower. Microorganisms that cause RMSF are transmitted through American canines and Rocky Mountain spotted fever mites.

  In order for microbial transmission to occur, mites need to attach to the dog or cat for at least 5 hours. Symptoms of RMSF can include fever, loss of appetite, depression, joint pain, lameness, vomiting, and diarrhea. Some animals may develop heart abnormalities, pneumonia, renal failure, liver damage, or even neurological signs (eg, seizures, staggers).

  Blood tests are used to detect antibodies against microorganisms. This indicates that the animal has been infected once in the past. Oral antibiotics are used for about 2 weeks to treat infections. Unlike Lyme disease, animals whose microorganisms have been eliminated usually recover and remain immune to subsequent infections. If the dog or cat has a damaged heart, liver, or kidney and / or if the nervous system is affected by an infection, additional supportive treatment at the hospital may usually be required .

  There are currently no vaccines available to prevent RMSF, and therefore tick control is important for animals that inhabit endemic areas.

  Ehrlichiosis is also a tick-borne disease that affects dogs. This is transmitted by brown dog tick and Lone Star Tick and is caused by rickettsiae microorganisms. This occurs all over the world and is recognized in every state of the United States. Common symptoms include depression, loss of appetite (anorexia), fever, joint stiffness and pain, and contusion. Typically, signs appear less than a month after tick biting and last for about 4 weeks.

  Special blood tests may be required to test antibodies against Ehrlichia. Antibiotics are usually given for up to 4 weeks to completely eliminate microorganisms. After infection, animals may have antibodies against microorganisms, but are not considered immune to reinfection. There is no vaccine available against ehrlichiosis. Low doses of antibiotics can be recommended for animals during the tick season in areas of the country where the disease is unique.

  Deer mites and western black mites carry bacteria that transmit canine anaplasmosis. Another form of anaplasmosis caused by different bacteria is carried by brown dog mites. Both dogs and cats are at risk for this condition. Because deer mites also carry other diseases, some animals may be at risk of developing multiple tick-borne diseases simultaneously.

  Symptoms of anaplasmosis are similar to ehrlichiosis, including joint pain, fever, vomiting, diarrhea, and possible nervous system disorders. Usually, pets begin to show signs of disease within a few weeks after infection. Diagnosis of anaplasmosis usually requires blood tests, urinalysis, and sometimes other specialized clinical tests.

  Depending on the severity of the infection, oral antibiotics are given for up to 1 month to treat anaplasmosis. Most pets recover completely if treated immediately. Immunity after suffering from anaplasmosis is not guaranteed, so pets can be reinfected when exposed again.

  Tick paralysis is caused by toxins secreted by mites. This toxin affects the mammalian nervous system. Affected dogs become weaker and lame, whereas cats are usually less affected. Symptoms begin about a week after the animal is initially bitten by a tick. Typically, this starts with hind limb weakness and eventually affects all limbs, after which it becomes difficult to breathe and swallow. If the condition progresses further, death may result.

  If ticks are found on the animal's body surface, they usually recover quickly by removal. Depending on the severity of the condition, supportive treatment (eg, respiratory assistance) may be required for survival. Antitoxins are available and can be given if the condition is discovered immediately after infection.

  Hemobartonellosis is a disease transmitted by both ticks and fleas. This is caused by microorganisms that target the red blood cells of affected animals, resulting in anemia and weakness. Both cats and dogs are affected. In cats, this condition is also known as feline infectious anemia. In dogs, the disease is usually not visually apparent unless the animal already has a potential problem.

  Diagnosis of hemobartonellosis is by examining blood samples for microorganisms. Special clinical tests are also available. Treatment with antibiotics must continue for several weeks, and some animals may require blood transfusions.

  Wild boar disease, also known as wild fever, is caused by bacteria carried by four species of mites in North America. Fleas can also transmit and transmit wild mania to dogs and cats. Cats are usually more susceptible to this condition than dogs. Dog symptoms are loss of appetite, depression, and mild fever. Cats show high fever, lymphadenopathy, nasal discharge, and sometimes abscesses at the site of tick bites. In general, young animals are at higher risk of contracting the disease.

  Blood tests are usually used to look for antibodies to bacteria that cause wild goose disease, and when this antibody is present, it is shown that it has been exposed and is almost certainly infected. Antibiotics are given to treat this condition in animals that have been confirmed positive. There is no prophylactic vaccine for this condition, so it is important to keep cats indoors and to use flea and tick control measures. Restricting pets from catching rodents, rabbits, and animals that carry the disease also helps protect the pet from suffering from the disease.

  When dogs and cats are diagnosed with babesiosis, protozoa, that is, very small unicellular animal microorganisms, are responsible groups. Mites transmit protozoan microorganisms to animals, which settle in red blood cells and cause anemia. Babesiosis is usually found in the southern United States, but is also present in the northeastern part of the country.

  Typically, the signs of canine babesiosis are severe. These include pale gingiva, depression, dark urine, fever, and lymphadenopathy. In severe cases, animals may fall suddenly and become shocked. Blood and urine tests, and special diagnostic tests are used to look for signs of microorganisms in affected animals.

  Usually, dogs that survive the disease remain infected and may recur in the future. No vaccine is available to protect against babesiosis.

  Cats are at risk of becoming infected with cytokes zone disease. This parasitic disease is transmitted through ticks and is more commonly reported in the southern central and southeastern regions of the United States. Typically, cats become seriously ill when infected. This is because parasites affect many parts of the body.

  Cats can develop anemia, depression, high fever, dyspnea, and jaundice (ie, yellowing of the skin). Treatment is often unsuccessful and dies just a week after infection.

  Typically, immediate and aggressive treatment with special drugs, intravenous infusion, and supportive care are required. A cat who has recovered from cytoskogenic disease can still be the owner of the disease for a lifetime. There is no vaccine against this disease and therefore prevention of ticks is important.

  Dogs in the southern central and southeastern regions of the United States have a greater risk of developing American canine hepatozone disease (ACH). Gulf Coast tick transmits this particular disease. This tick-borne disease is caused by the actual ingestion of larvae or adult ticks, rather than by infection via tick attachment and bites on the skin. Ingestion is suspected to occur while grooming yourself or when a dog eats an infected animal.

  Infection is severe and often fatal. Symptoms include high fever, stiffness and pain during exercise, weight loss, and complete loss of appetite. The muscles begin to weaken and the most obvious appearance is around the dog's head. It also happens very often in the eyes.

  Tests can be performed to find parasites in dog blood, secretions, or muscle tissue. For some time after diagnosis, treatment with anti-parasitic drugs along with anti-inflammatory drugs and antibiotics is necessary. If the dog recovers, the disease can recur and may require continued drug treatment for several years.

  The most common problem with fleas in both cats and dogs is flea allergic dermatitis. The flea injects saliva into the skin while eating, which causes the animal to feel itchy where the salivary protein is deposited at the bite site. Subsequent scratching behavior can cause significant hair loss at the bite site.

  Tick causes several diseases in both cats and dogs, but only dogs have Lyme disease. Cats can suffer from anaplasmosis and barbarism. Although rare, ticks can infect cats with Rocky Mountain spotted fever.

  The following examples are provided as illustrations of the present invention and should in no way be considered limiting.

Example 1 Flea / tick formulation Exemplary formulation
(A) 4.95 g of dinotefuran and 60.0 g of etofenprox are dissolved in 54.6 g of N-octylpyrrolidone. This solution can be stored at ambient temperature for at least one month. Alternatively, a dry mixture of dinotefuran and etofenprox each having a mass to weight ratio of 0.0825 with N-octylpyrrolidone to mix in amounts that achieve a weight percent ratio of up to 60% etofenprox and 4.95% dinotefuran. Can also be shipped separately.

  (B) N-methylpyrrolidone 34 selected to provide a solution in which the weight percent ranges are etofenprox 40-60%, dinotefuran 4.95%, pyriproxyfen 0.44%, and N-octylpyrrolidone 6-10% Dissolve 4.95 g of dinotefuran, 40-60 g of etofenprox, and 0.44 g of pyriproxyfen in ~ 48 g and 6-10 g of N-octylpyrrolidone. This solution is stable for at least 1 month at ambient temperature.

  (C) N selected to provide a solution in which the weight percent ratio is etofenprox 40-60%, dinotefuran 4.95%, pyriproxyfen 0.44%, piperonyl butoxide 0.2%, and N-octylpyrrolidone 6-10% Dissolve 4.95 g of dinotefuran, 40-60 g of etofenprox, 0.44 g of pyriproxyfen and 0.2 g of piperonyl butoxide in 34-48 g of methylpyrrolidone and 6-10 g of N-octylpyrrolidone. This solution is stable for at least 1 month at ambient temperature.

Example 2 Application of High Flea / Tick Formulations The formulations of Examples 1 (A-C) were prepared in N-octylpyrrolidone / N-methylpyrrolidone solvent and nominally 60-65% strength by weight dinotefuran. And etofenprox, and optionally less than 0.5% by weight of pyriproxyfen and piperonyl, respectively. Topical application is made once a month to dogs or cats at dosages of 0.5-8 ml, preferably 1.2 ml up to 5.96 ml, depending on the animal's body weight.

Example 3 Medication Application in Dogs Typically, the formulation of Example 1 is applied to canines based on body weight. Table 6 shows typical dosages for topical formulations in which the mass weight percent of etofenprox is 55%. The product can be applied as a spot at the base of the neck between the scapulas or in a streak shape starting from the base of the neck and ending at the base of the tail.

Example 4 Medication Application in Cats With the exception of kittens, cat body weights do not show the same variation as dog body weights. The 40 wt% etofenprox formulation prepared as in Example 1 is applied at a dosage of 1.8 ml. The product can be applied as a spot at the base of the neck near the scapula or in a streak shape starting from the base of the neck and ending at the base of the tail.

(Table 1) Number of cats and dogs

(Table 2)

(Table 3)

ニテンピラムおよびジノテフランは水溶性が高く、親水性と説明され得る。 (Table 4)

Nitenpyram and dinotefuran are highly water soluble and may be described as hydrophilic.

(Table 5) Storage in the room (Ambient), freezer, and refrigerator

(Table 6)

Claims (15)

A composition comprising a hydrophilic neonicotinoid component and an ether pyrethroid component that are soluble in an aprotic polar solvent, and an aprotic polar solvent,
The composition is a solution;
The ether pyrethroid component is etofenprox,
The hydrophilic neonicotinoid component is dinotefuran,
The aprotic polar solvent is a combination of N-octylpyrrolidone and N-methylpyrrolidone,
Etofenprox has a weight percent of 55 to 65 weight percent;
% By weight of di Notefuran is Ri 4 to 6% by weight of Der,
The weight percentage of N-octylpyrrolidone is 6 to 10% by weight,
Composition.   The composition of claim 1 further comprising an insect growth regulator.   The composition further comprising 0.1-0.3 weight percent synergist to enhance ether pyrethroid activity, wherein the synergist is selected from piperonyl butoxide and n-octylbicycloheptene dicarboximide. A composition according to 1.   The composition according to claim 2, wherein the insect growth regulator is pyriproxyfen, methoprene, or phenoxycarb.   The composition of claim 2, wherein the weight percent of hydrophilic neonicotinoid, ether pyrethroid, and insect growth regulator comprises 55 to 65 weight percent in an aprotic polar solvent.   The composition of claim 1, wherein the weight percent of etofenprox is 60 weight percent.   The composition of claim 4, wherein the weight percentage of pyriproxyfen is 0.3-0.5 wt%.   A method for topically treating fleas and ticks in a fur animal comprising the step of topically administering an effective amount of the composition of claim 5.   9. The method of claim 8, wherein a small amount is administered topically to a cat or dog.   The method according to claim 9, wherein the amount is 1 to 8 ml.   12. The method of claim 10, wherein the amount is administered regularly every 30-60 days. 55 to 65 weight percent etofenprox, 4 to 5 weight percent dinotefuran, and optionally 0.3 to an aprotic polar solvent that is a combination of N-methylpyrrolidone and 6 to 10 weight percent N-octylpyrrolidone A kit for treating fleas and ticks in an animal comprising a solution in which -0.5 weight percent pyriproxyfen is dissolved.   The kit of claim 12 further comprising 0.3 to 0.5 weight percent pyriproxyfen.   14. The kit of claim 13, further comprising 0.1 to 0.3 weight percent piperonyl butoxide or n-octylbicycloheptene dicarboximide.   13. Kit according to claim 12, comprising a individually containerized solution in an amount selected from 0.5-8 ml for spot treatment of cats or dogs.