US 2015O164864A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2015/0164864 A1 Soll et al. (43) Pub. Date: Jun. 18, 2015 (54) PARASITICIDAL ORAL VETERINARY Publication Classification COMPOSITIONS COMPRISING SYSTEMICALLY-ACTING ACTIVE AGENTS, (51) Int. Cl. METHODS AND USES THEREOF A613 L/42 (2006.01) A63/94 (2006.01) (71) Applicant: MERIAL LIMITED, DULUTH, GA A619/00 (2006.01) (US) (52) U.S. Cl. CPC ............... A61K 31/42 (2013.01); A61 K9/0056 (72) Inventors: Mark David Soll, Alpharetta, GA (US); (2013.01); A61 K31/194 (2013.01) Diane Larsen, Buford, GA (US); Susan Mancini Cady, Yardley, PA (US); Peter (57) ABSTRACT Cheifetz, East Windsor, NJ (US); This invention relates to veterinary compositions for treating Izabela Galeska, Newtown, PA (US) and/or preventing fleas or ticks infection or infestation in an animal comprising an isoxazoline active agent of Formula (73) Assignee: MERIAL LIMITED, DULUTH, GA (II): (US) (21) Appl. No.: 14/627,499 C O-N O (22) Filed: Feb. 20, 2015 FC Related U.S. Application Data C (62) Division of application No. 13/754.969, filed on Jan. C CH3 31, 2013. (60) Provisional application No. 61/595,463, filed on Feb. or a pharmaceutically acceptable salt thereof, and a pharma 6, 2012. ceutically acceptable carrier. Patent Application Publication Jun. 18, 2015 Sheet 1 of 3 US 2015/O164864 A1 ( ;............................................................................................................. 8. &S 8( ;...............................:8.............................................................. ason::::ti: 8. is 8-8- xx 88):&:38: xx 3:3:::::s s $ 40 to w. x3 &::::::: : 8:y:::::: 2 : { ir anim:::::8: -xx 8::::::s w8w 3 88; its 88:::::::s Figure 2. Average Dissolution of 2g Chewables Stored at 40°C/75% RH Patent Application Publication Jun. 18, 2015 Sheet 2 of 3 US 2015/O164864 A1 68883:s Figure 3. Average Dissolution of 4g Chewables Stored at 25°C/60% RH :www. 88: - - - - - - - - - - - - - - - - - - - - - - - - 2 :::::::RS 48 or 8vo;:S Figure 4. Average Dissolution of 4g Chewables Stored at 40°C/75%RH Patent Application Publication Jun. 18, 2015 Sheet 3 of 3 US 2015/O164864 A1 are 28 ngfxg Chewaiie Fornisati; where 48 gfxg Chesaixie for:tiatio --25 gfxg E3 fittharic: Sction: 2 3 4. s 8. 7 fire bay : Figure 5: Plasma Concentration of Compound A from Chewable Compositions" US 2015/0164864 A1 Jun. 18, 2015 PARASITICIDAL ORAL VETERINARY humans include those of the genera Ancylostoma, Necator, COMPOSITIONS COMPRISING Ascaris, Strongyloides, Trichinella, Capillaria, Toxocara, SYSTEMICALLY-ACTING ACTIVE AGENTS, Toxascaris, Trichuris, Enterobius, Haemonchus, Trichos METHODS AND USES THEREOF trongylus, Ostertagia, Cooperia, Oesophagostomum, Bunos tomum, Strongylus, Cyathostomum, and Parascaris among CROSS REFERENCE TO RELATED others, and those that are found in the blood vessels or other APPLICATIONS tissues and organs include Onchocerca, Dirofilaria, Wuchere 0001. This application is a divisional of, and claims benefit ria and the extra intestinal stages of Strongyloides, Toxocara of co-pending U.S. patent application Ser. No. 13/754,969. and Trichinella. Therapeutic agents are administered to ani filed Jan. 31, 2013, which claims the benefit of U.S. Provi mals by a variety of routes. sional Application Ser. No. 61/595,463, filed Feb. 6, 2012, 0013 These routes include, for example, oral ingestion, which are incorporated herein by reference in their entirety. topical application or parenteral administration. The particu lar route selected by the practitioner depends upon factors FIELD OF THE INVENTION Such as the physicochemical properties of the pharmaceutical ortherapeutic agent, the condition of the host and economics. 0002 The present invention provides oral veterinary com In certain cases, it is convenient and efficient to administer positions comprising at least one systemically-acting active Veterinary medicines orally by placing the therapeutic agent agent for controlling ectoparasites and/or endoparasites in in a solid or liquid matrix that is suitable for oral delivery. animals; the use of these compositions to control ectopara These methods include chewable drug-delivery formulations. sites and/or endoparasites, and methods for preventing or The problem associated with administering oral formulations treating parasitic infections and infestations in animals. to animals is that the therapeutic agent often provides an unpleasant taste, aroma, or texture, which causes the animals BACKGROUND OF THE INVENTION to reject the composition. This is further exacerbated by com 0003 Animals including mammals and birds are often positions that are hard and difficult to swallow. Susceptible to parasite infestations/infections. These para 0014 Oral veterinary compositions in the form of soft sites may be ectoparasites or endoparasites. Domesticated chewable compositions (“soft chews'), or chewable tablets animals, such as cats and dogs, are often infested with one or that are palatable are usually convenient to administer to more of the following ectoparasites: certain animals, particularly cats and dogs, and may be used 0004 fleas (e.g. Ctenocephalides spp., such as Cteno effectively to dose veterinary medicine to these animals. cephalides fells and the like): However, many oral compositions comprising active agents 0005 ticks (e.g. Rhipicephalus spp., Ixodes spp., Der with a bitter or unpleasant taste are not well accepted by cats macentor spp., Amblyoma spp., Haemaphysalis spp., and dogs. Furthermore, when the bioavailability of an active and the like): agent from an oral dosage form is not sufficient or is variable, 0006 mites (e.g. Demodex spp., Sarcoptes spp., Oto the required exposure of the animal to the active ingredient dectes spp., Cheyletiella spp., and the like); may not be sufficient to provide the desired efficacy. Problems 0007 lice (e.g. Trichodectes spp., Felicola spp., Linog such as these often lead to low or sub-optimal efficacy and nathus spp., and the like); control of parasites. 0008 mosquitoes (Aedes spp., Culex spp., Anopheles 0015 Chewable dosage forms for drug delivery are well spp. and the like); and known to pharmaceutical technology. It is known in the phar 0009 flies (Musca spp., Stomoxys spp., Dermatobia maceutical industry that the act of chewing increases the spp., and the like). Surface area of the available active ingredient and may 0010 Fleas are a problem because not only do they increase the rate of absorption by the digestive tract. Chew adversely affect the health of the animal or human, but they able systems are also advantageous where it is desirable to also cause a great deal of psychological stress. Moreover, make an active ingredient available topically to the mouth or fleas may also transmit pathogenic agents to animals and throat areas for both local effects and/or systemic absorption. humans, such as tapeworm (Dipylidium caninum). Further, chewable dosage forms are also utilized to ease drug 0011 Similarly, ticks are also harmful to the physical and/ administration in pediatric and geriatric patients. Examples or psychological health of the animal or human. However, the of chewable dosage forms may be found in U.S. Pat. Nos. most serious problem associated with ticks is that they are 6,387,381; 4,284,652; 4,327,076; 4,935,243; 6,270,790: vectors of pathogenic agents affecting both humans and ani 6,060,078; 4,609.543; and, 5,753,255, all incorporated herein mals. Major diseases which may be transmitted by ticks by reference. include borreliosis (Lyme disease caused by Borrelia burg 0016 Palatability and “mouth feel are important charac dorferi), babesiosis (or piroplasmosis caused by Babesia teristics to be considered in providing a dosage form, or spp.) and rickettsioses (e.g. Rocky Mountain spotted fever). matrix, for an active pharmaceutical or medicinal. Unfortu Ticks also release toxins which cause inflammation or paraly nately, many pharmaceuticals and other active ingredients sis in the host. Occasionally, these toxins may be fatal to the have a bitter or otherwise unpalatable taste, or an unaccept host. able mouth feel, due to the grittiness or chalkiness of the 0012 Animals and humans also suffer from endoparasitic compound, or both. These characteristics make it difficult to infections caused by parasitic worms categorized as cestodes incorporate Such active ingredients into the current state of (tapeworms), nematodes (roundworms) and trematodes (flat the art for chewable dosage forms because the objectionable worms or flukes). These parasites cause a variety of patho taste and/or mouth feel make it less likely to obtain compli logic conditions in domestic animals including dogs, cats, ance by the user. Oral Veterinary dosage forms that are not pigs, sheep, horses, cattle and poultry. Nematode parasites palatable to the animal treated result in low acceptance of the which occur in the gastrointestinal tract of animals and medicament by the animal and a low level of compliance. US 2015/0164864 A1 Jun. 18, 2015 Thus, there is a need for improved oral veterinary dosage tions, and product sheets for any products mentioned herein forms that are palatable and well accepted by the treated or in any document incorporated by reference herein, are animal. hereby incorporated herein by reference, and may be 0017. Another challenge with oral veterinary composi employed in the practice of the invention. tions, particularly Soft chewable compositions, is that the 0025 Citation or identification of any document in this release