HK40079612A - Palatable soft-chew - Google Patents

Description

Palatable soft chews

Cross Reference to Related Applications

This application is an international application filed under the patent cooperation treaty claiming priority from us 62/897,094 provisional patent application filed 2019 on 6.9.9, the contents of which are incorporated herein by reference in their entirety.

The present invention relates to a palatable soft chew comprising at least one active agent, at least one wetting agent, and at least one flavoring agent, and methods for controlling or treating a condition in an animal comprising administering said composition to said animal in need thereof.

Background

There is a continuing need to develop effective, highly palatable dosage forms for delivering active veterinary ingredients to animals.

The ease of administering oral veterinary drugs to animals is a major aspect of owner compliance and has a significant impact on the health of the animals. The willingness of an animal to voluntarily ingest a drug depends on the palatability of the dosage form.

When the owner or trainer places the veterinary drug in a feeding bowl or other container, or in an extended hand, it is necessary for the animal to voluntarily and freely choose to receive and eat the drug. However, most oral drugs have a bitter taste and/or an unpleasant odor for the animal, which makes it difficult to feed the animal.

The palatability of veterinary dosage forms is determined by the smell, taste and sensation of the drug in the oral cavity (commonly referred to as "good mouthfeel"). Generally, palatability is achieved by adding flavor enhancers to the formulation during the manufacturing process.

Animal owners and domesticators typically administer oral medications by one of four methods.

First, owners and veterinarians can inject liquid oral drugs directly into the throat of an animal. Second, owners and domesticated animals may add oral medications in the form of liquid drops to the food of the animal. Third, owners and domesticated veterinarians can orally administer oral medications to animals in the form of liquid drops.

Finally, owners and domesticators may employ the "poke down" method. If the animal loses appetite or the drug cannot be administered with food, the owner or veterinarian will undertake the unpleasant task of poking the solid dosage form (e.g., tablet or capsule) into the throat of the animal. Owners and domesticators may find it easier to prevent large dogs from twisting by riding on the dog and holding their shoulders stably between the knees of the owner and domesticator, while ensuring that the weight is not pressed against the back of the dog. The owner or trainer must grasp the top of the animal's mouth and nose with one hand and carefully pull down the chin with the other hand. The owner or beast-trainer must quickly dig the tablet or capsule as deep as possible into the throat of the animal and close his mouth, hold the mouth tightly with one hand while gently stroking the throat with the other hand until the animal swallows.

Each of these methods requires enforcement, and/or spoofing. Compliance and therefore success rate of treatment will be greatly reduced if the animal is not hungry or particularly resistant. These methods are extremely challenging for the owner, especially if fasting administration is required or if long-term administration is required. Accordingly, chewable solid palatable dosage forms are preferred.

Common chewable solid dosage forms comprise hard chewable compressed tablets, which typically include a palatability enhancer and a coating for improved palatability. However, dosage form texture must also be considered during the manufacturing process.

Hard chewable compressed tablets tend to be gritty or otherwise unattractive to animals. Typically, animal owners and domesticators must still resort to the "under the poke" approach of hard chews, or to hiding hard chews in other food or snack foods, even though hard chews are sold as chewable dosage forms. However, hard chews do have the advantage of shelf stability.

There is a need to improve the formulation of veterinary active agents into desirable edible medicaments, such as palatable soft chewable dosage forms, to increase the voluntary acceptance of veterinary medicaments by animals.

In particular, there is a need for soft chewable dosage forms having an extended shelf life, i.e., soft chewable compositions that maintain suitable softness and rapid disintegration for weeks or even months after manufacture.

Disclosure of Invention

The present inventors have found that the soft chew compositions described herein exhibit high palatability, and thus high animal acceptance and owner compliance.

The present invention provides soft chew compositions comprising

(a) At least one odorant;

(b) at least one wetting agent;

(c) at least one active ingredient;

and optionally also (c) a second set of one or more of,

(d) and (3) water.

The present disclosure further provides methods of treating an animal having a disease or condition comprising administering to the animal a soft chew composition of the present disclosure.

Further objects, features and advantages of the present invention will become apparent from the detailed description that follows.

Detailed Description

Applicants have now found that the soft chewable dosage forms of the present invention show excellent acceptance in animals.

The soft chew compositions of the present disclosure maximize the use of palatable components, rather than typical pharmaceutical ingredients, to achieve high palatability.

The taste and smell of typical pharmaceutical ingredients may not be appealing to animals, which may result in poor compliance.

Thus, the soft chew compositions of the present disclosure can achieve high drug loading and produce excellent drug effects in treated animal subjects.

Commercial veterinary products typically take at least 17 minutes to disintegrate and in many cases more than 60 minutes.

The improved disintegration time allows for absorption of various active pharmaceutical ingredients across the gastrointestinal system, and may prevent the dosage form from passing intact through the animal subject.

By "animal" is meant an individual animal belonging to a mammal, reptile or bird. In one aspect, the soft chew compositions of the present invention may be administered to an animal.

In another aspect, the palatable soft chew compositions of the present invention may be administered to a mammal or bird.

In another aspect, the palatable soft chew compositions of the present invention may be administered to animals such as dogs, cats, horses, pigs, llamas, rabbits, goats, sheep, deer, elk, cattle and poultry.

By "subject" is meant an animal to which the soft chew compositions of the present invention are administered for the treatment, prevention and/or amelioration of a disease or condition and/or symptom thereof.

By "soft chew composition" or "soft chew dosage form" is meant a soft dosage form that an animal is able to chew and ingest. The soft chew compositions of the present invention generally have a texture and consistency like meat, similar to fillings widely found in edible pet treats, with softness or palatability similar to cooked meat. Edible soft chews are typically made by blending and extrusion, blending and tapping, injection molding, compression, tableting, molding, and other manufacturing methods.

By "pharmaceutically acceptable" it is meant that the ingredient, substance, or composition must be chemically and/or toxicologically compatible with the formulation, composition, and/or other ingredients in the animal being treated therewith.

For use in the present invention, the inactive ingredients of the edible soft chews should not be below food grade quality and may be of higher quality (e.g., USP or NF grade). In this context, "food grade" means that the material does not contain or impart health hazardous chemicals or agents. Thus, a food-grade flavoring, if derived from an animal, would be a flavoring that has been prepared to substantially reduce or eliminate the presence of infectious agents or contaminants therein; for example, by methods such as pasteurization, pressurization, or irradiation.

The latter method is particularly effective in eliminating infectious agents such as Escherichia coli, Salmonella, and Campylobacter from various foods and animal-derived materials such as raw meat products, vegetables, grains, and fruits. However, in one aspect of the invention, the edible soft chews of the present invention will not contain any animal derived ingredients, and/or will not contain any animal derived flavoring agents. All ingredients should be pharmaceutically acceptable (e.g., food grade, USP or NF as the case may be).

By "palatability enhancer" is meant an inactive flavoring ingredient that induces a pet to eat a food, snack, supplement, or veterinary drug. The odorant to be used in the composition of the present invention may take the form of a dry powder odorant, a non-powder odorant, or as a system using both dry powder and non-powder odorants.

In one aspect, the soft chew compositions of the present invention comprise a dry powder flavor enhancer. Suitable palatable powders comprise plant and animal derived flavors and meat analogue flavors. In one aspect, the compositions of the present invention include a flavoring agent derived from fruit, vegetable, beef, poultry, fish, and/or meat analogue flavors.

In one aspect, the soft chewable composition of the invention comprises one or more palatable powders selected from sugar, sugar substitutes, salt, bone marrow, blood meal, by-product powders, flavor powders or liquids, apple powder, bean powder, beet powder, pepper powder, blueberry powder, broccoli powder, squash powder, cabbage powder, carrot powder, broccoli powder, celery powder, radish powder, chive powder, corn powder, cranberry powder, dill powder, kale powder, leek powder, lemon powder, mushroom powder, onion powder, tangerine powder, potato powder, pea powder, pumpkin powder, onion powder, potato powder, tomato powder, spinach powder, mucic acid pulp powder, sweet potato powder, zucchini powder, other vegetable or fruit powders, and/or natural and artificial meat powders including liver powder and artificial beef, and commercially available flavor enhancers.

In another aspect, the soft chew composition of the present invention comprises a flavor enhancer selected from blueberry powder, carrot powder, sweet potato powder, liver powder, and/or beef.

On the other hand, the flavoring agents to be used in the soft chew compositions of the present invention may alternatively be granules or chips, rather than powders.

In one aspect, the soft chew compositions of the present invention comprise one or more non-powder flavoring agents, such as yeast, yeast extract, tapioca syrup, honey and/or salt.

In one aspect, the soft chew compositions of the present invention comprise a total amount of from 1% to 90%, or from 10% to 80%, or from 20% to 70%, or from 30% to 60%, of one or more flavoring agents, based on the total weight of the soft chew composition.

In one aspect, the soft chew compositions of the present invention may comprise salt and/or sugar that are known to be very palatable to dogs.

By "pharmaceutically effective amount" is meant a non-toxic amount of the active ingredient that is sufficient to produce the beneficial or desired results described herein when administered to a subject. Effective administration-i.e., feeding the soft chew composition to a subject animal-and dosages can be determined empirically, and making such determinations is within the skill of the art. It will be understood by those skilled in the art that the dosage will vary with the rate of excretion, the duration of treatment, the identity of any other drug being administered, the age, size and species of the animal, and similar factors well known in the veterinary pharmaceutical art. Generally, a suitable dose of a composition according to the invention will be the amount of the composition which is the lowest dose effective to produce the desired effect with no or minimal side effects.

The amount of active ingredient depends on the active ingredient, the animal to be treated, the condition status of the animal and the severity of the condition. Determination of these factors is well within the skill of those in the veterinary arts.

"active ingredient" is to be understood in its normal sense and covers pharmaceutically acceptable and therapeutically effective ingredients for the treatment of the animal body, as well as combinations of one or more such agents. In one aspect, the soft chewable composition of the invention may comprise any active ingredient suitable for oral ingestion. In one aspect, the soft chew compositions of the present invention, including at least one active ingredient, may comprise agents such as antiparasitic agents (in vivo or in vitro), acaricides, anthelmintics, insecticides, antimicrobial agents, antiviral agents, antibacterial agents, anti-inflammatory agents, psychotherapeutic agents, proton pump inhibitors, analgesics, antiallergics, antihypertensives, and any other active ingredient useful in the treatment of a condition in an animal.

The active ingredient may be, for example, one or more acaricides selected from the group of acaricides consisting of: antibiotic acaricides such as avermectin (abamectin), doramectin (doramectin), emamectin (enametin), eprinomectin (eprinomectin), ivermectin (ivermectin), lepimectin (lepimectin), milbemectin (milbemectin), nikkomycin (nikkomycin), selamectin (selamectin), acaricidal (tetranectin) and thuringiensin (thurienginin); bridged biphenyl acaricides, such as azobenzene (azobenzone), fenpyroximate (benzoximate), benzyl benzoate (benzobenzoate), bromopropylate (bromopropylate), chlorodicofol (chlorobensenide), chlorfenapyr (chlorofenthol), chlorfenapyr (chlorofenton), dinotefuran (chlorofenulphde), ethylbenzofenapyr (chlorobenzilate), propylfenapyr (chloropropyrate), dicofol (dicofol), diphenyl sulfone (diphenyl sulfone), phenoxyacetylene (donax), fenaminostrobin (fenton), fluoronitrodiphenylamine (fennifanil), fluoromiticide (fluorobenicide), prochlorol (procalon), tetrachlorfenuron (tetradifenon) and thioethers (tetrasul); carbamate acaricides such as benomyl (benomyl), carbosulfan (carbalate), carbaryl (carbaryl), carbofuran (carbofuran), fenothiocarb (fenothiocarb), methiocarb (methiocarb), metolcarb (metalocarb), lufenuron (promacyi) and propoxur (propoxyur); oxime carbamate acaricides such as aldicarb, butocarboxim, oxamyl, carboxim and thiofanox; dinitrophenol acaricides such as binacryl (binaprocyl), dinex (dinobuton), dinocap (dinocap), dinocap-4 (dinocap-4), dinocap-6 (dinocap-6), dinocap (dinocoton), nitryl (dinopenton), nitrooctyl (dinosulfon), nitrobutyl nitrate (dinoterbon) and DNOC; formamidine acaricides such as amitraz, chlordimeform, chlorfenapyr, formamidine and carboximidamide; mite growth regulators such as clofentezine (cbfentezine), propargite (dofenapyn), fluazuron (fluazuron), flutriathiane (flubenzine), flucycloxuron (flucycloxuron), flufenoxuron (flufenoxuron), and hexythiazox (hexythia-zox); organochlorine acaricides such as bromhexine (bromocylen), toxaphene (camphechlor), dichlofen (dienochlor) and endosulfan (endosulfan); organotin acaricides such as azocyclotin (azocyclotin), tricyclazole tin (cyclohexatin) and fenbutatin oxide (fenbutatin oxide); pyrazole acaricides such as acetoprole (acetoprole), fipronil (fipronil) and its analogues and derivatives, tebufenpyrad (tebufenpyrad) and flupyrad (vaniprole); a pyrethroid acaricide, comprising: pyrethroid acaricides such as fluthrin (acrinathrin), bifenthrin (bifenthrin), cyhalothrin (cyhalothrin), cypermethrin (cypermethrin), alpha-cypermethrin (alpha-cypermethrin), fenpropathrin (fenpropathrin), fenvalerate (fenvalete), flucythrinate (flucythrinate), flumethrin (fluorine-thrin), fluvalinate (fluvalinate), fluvalinate (tau-fluvalinate), and permethrin (permethrin), and pyrethroid ether acaricides such as benzyl ether (halofenprox); quinoxaline miticides such as chlormequat and diclofen; sulfite acaricides, such as propargite (propargite); tetronic acid acaricides, such as spirodiclofen (spirodiclofen); and form unsorted acaricides such as fenaminoquinone (acequizamide), sulfadimidine (amidoflumet), arsenic trioxide (arsenous oxide), chlorbenzuron (chloromethuron), closantel (closantel), crotamiton (crotamiton), diafenthiuron (diafenthiuron), dichlofluanid (dichlofluanid), disulfiram (disulphiram), anti-acarid (fenzaflor), fenazaquin (fenazazan), fenpyroximate (fenpyroximate), fluypyrim (flunetoil), metrafenm (mesulfen), MNAF, fluthrin (nifuride), pyridaben (pyrineb), pyrimethanil (pyrimethanil), sumiram (sulfenamide), fluthiabendamide (fluthiabendazole (thiabendamine), thifenthixene (thiabendazole).

Suitable insecticides can be selected from a variety of well-known different chemical classes, such as chlorinated hydrocarbons (chlorinated hydrocarbons), organophosphates (organophosphates), carbamates (carbamates), pyrethroids (pyrethides), formamidines (formamidines), borates (borates), phenylpyrazoles (phenylpyrazoles) and macrolides (macrocyclics lactones). Outstanding insecticides include imidacloprid (imidacloprid), fenthion (fenthion), fipronil (fipronil), allethrin (allethrin), resmethrin (resmethrin), fenvalerate (fenvalete), permethrin (permethrin), malathion (malathion), and derivatives thereof. According to one embodiment, the insecticide is a neonicotinoid insecticide, such as acetamiprid (acetamiprid), clothianidin (clothianidin), dinotefuran (dinotefuran), imidacloprid (imidacloprid) (as described above), nitenpyram (nitenpyram), thiacloprid (thiacloprid), and thiamethoxam (thiamethoxam). Insect Growth Regulators (IGR) widely used include, for example, benzoylphenylureas (benzoylphenylureas), such as diflubenzuron (diflubenzuron), lufenuron (lufenuron), noviflumuron (noviflumuron), hexaflumuron (hexaflumuron), triflumuron (triflumuron) and teflubenzuron (tefibenzu), or substances such as fenoxycarb (fenoxycarb), pyriproxyfen (pyriproxyfen), methoprene (methoprene), methoprene (kinoprene), hydroprene (hydroprene), cyromazine (cyromazine), buprofezin (buprofezin), pymetrozine (pymetrozine) and derivatives thereof.

Suitable anthelmintics may be selected from the group consisting of in vivo anthelmintics and in vitro and in vivo insecticides comprising: macrolides (macrolides), benzimidazoles (benzimidazoles), benzimidazole precursors (pro-benzimidazoles), imidazothiazoles (imidazothiazoles), tetrahydropyrimidines (tetrahydropyrimidines), organophosphates (organophosphates), piperazines (piperazines), salicylanilides (salicylanilides), and cyclic depsipeptides (cyclic depsipeptides).

Suitable anthelmintics include broad spectrum macrolides such as avermectins (avermectins), milbemycins (milbemycins), and derivatives thereof, including ivermectin, doramectin, moxidectin (moxidectin), selamectin, emamectin, eprinomectin, milbemectin, abamectin, milbemycin oxime, nemadectin (nemadectin), and derivatives thereof, in free form or in pharmaceutically acceptable salt form. Benzimidazoles, benzimidazole carbamates and benzimidazole precursors include effective compounds such as thiabendazole (thiabendazole), mebendazole (mebendazole), fenbendazole (fenbendazole), oxfendazole (oxfendazole), oxibendazole (oxbendazole), albendazole (albendazole), luxabendazole (luxabendazole), netobimin (netobimin), parbendazole (parbendazole), flubendazole (flubendazole), cyclobendazole (cyclobendazole), febantel (febantel), thiophanate (thiophanate) and derivatives thereof. Imidazothiazoles contain highly active compounds such as tetramisole, levamisole and derivatives thereof. Tetrahydropyrimidines contain highly active compounds, such as morantel, pyrantel and their derivatives. Organophosphates contain effective compounds such as dichlorvos (dichlorvos), haloxon (haloxon), trichlorfon (trichlorfon), and derivatives thereof. Salicylanilides comprise highly active compounds such as closantel, tribromosalan, dibromsalan, hydroxychlorosalicylanilide, cloioxanide, iodoethersalicylamide, bromothiosalicylamide, bromoflunix and derivatives thereof. Cyclic depsipeptides encompass compounds consisting of amino acids and hydroxycarboxylic acids as cyclic structural units and 6 to 30 ring atoms, such as PF 1022A, emerdoside (emodepside), and others described in U.S. patent No. 6,159,932, which is incorporated herein by reference for all relevant purposes.

Suitable antimicrobial active ingredients include various penicillins (penicillins), tetracyclines (tetracyclines), sulfonamides (sulfonamides), cephalosporins (cephalosporins), aminoglycosides (aminoglycosides), trimethoprim (trimethoprim), dinimethalin (dimetridazoles), erythromycin (erythromycins), neomycin b (framycetin), furazolidone (fruazolidinone), various pleuromutilins, such as tiamulin (thiamorpholin), valnemulin (valnemulin), various macrolides, streptomycin (streptomycin), polypoly (clinol), salinomycin (salinomycin), monensin (monensin), halofuginone (halofuginone), methylcalimycin (narasin), guanidinium (chlorobenzenedione), quinolones (quinolones), and the like. Quinolones, preferably fluoroquinolones, comprise compounds as disclosed in the following U.S. patents: 4,670,444, 4,472,405, 4,730,000, 4,861,779, 4,382,892, and 4,704,459, which are incorporated herein by reference. Specific examples of fluoroquinolones include: pefloxacin (benofloxacin), binofloxacin (binofloxacin), cinoxacin (cinoxacin), ciprofloxacin (ciprofloxacin), danofloxacin (danofloxacin), difloxacin (difloxacin), enoxacin (enoxacin), enrofloxacin (enrofloxacin), fleroxacin (fleroxacin), ibafloxacin (ibafloxacin), levofloxacin (levofloxacin), lomefloxacin (lomefloxacin), marbofloxacin (marofloxacin), moxifloxacin (moxifloxacin), norfloxacin (norfloxacin), ofloxacin (ofloxacin), orbifloxacin (orbifloxacin), pefloxacin (floxacin), temafloxacin (temafloxacin), tosufloxacin (floxacin), floxacin (florafloxacin) and sarafloxacin (sparfloxacin). As a further example of an antibacterial fluoroquinolone for animals, pradofloxacin (pradofloxacin) may be mentioned. Other specific examples of quinolones include pipemidic acid (pipemidic acid) and nalidixic acid (nalidixic acid).

Other drugs or nutritional agents known in the veterinary art (e.g., vitamin and mineral supplements) are also suitable active ingredients.

For example, the soft chew compositions of the present invention may include as active ingredients one or more nutritional agents such as omega 3 fatty acids, omega 6 fatty acids, methylsulfonylmethane (methylsulfonylmethane), glucosamine HCl, chondroitin sulfate and manganese ascorbate, st. john's word, vegetable glycerin, green foods, probiotics and antioxidants such as vitamins C and E, beta carotene and selenium, as well as any other vitamins, minerals or other dietary or nutritional supplements that can be formulated into the soft chew compositions of the present invention.

Pharmaceutically acceptable salts of any of the active ingredients may be used in the soft chewable compositions disclosed herein, if feasible. In addition, prodrugs of one or more active ingredients may also be used in the soft chew compositions disclosed herein.

In one aspect, the soft chew compositions of the present invention comprise one or more active ingredients selected from the group consisting of anti-inflammatory agents and parasiticidal (i.e., anthelmintic) agents.

In another aspect, the soft chew compositions of the present invention comprise a parasiticidal active ingredient selected from the group consisting of: abamectin, albendazole, clorsulon (clorsulon), closantel, dichlorophen (dichlorophene), dimalectin (dimadectin), doramectin, emeraldide (emodepside), emamectin, eprinomectin, febantel, fenbendazole, imidacloprid, ivermectin, latidectin, lepimectin, levamisole, lufenuron, milbemycin oxime, moxidectin, nitrothionate, oxattal (oxantel), oxybenzoxazole, piperazine, pyrantel, praziquantel, selamectin, spinosad, triclabendazole, salts and derivatives thereof.

In one aspect, the soft chew compositions of the present invention comprise an anti-inflammatory active ingredient selected from carprofen, dexamethasone, ketoprofen, meloxicam, medadam, naproxen, nimesulide, pentoxyfilline, phenylbutazone, prednisolone, prednisone, robekoxib, sulfasalazine, tolfenamic acid, salts and derivatives thereof.

In certain embodiments, the soft chew compositions of the present invention do not include as active ingredients: epothilones (apoquel), sarolaner (sarolaner), alfuraner (afoxoraner), fluralafenaner (fluralaner), loratadine (lotilaner), malachite (maropitant), paracetamol (acetaminophen), ibuprofen (ibuprolen), flurbiprofen (flurbiprofen), clavulan (clavamox), naproxen, meloxicam, ketoprofen, phenylpropanolamine, chlorpheniramine maleate (chlorpheniramine maleate), dextromethorphan (dextromethorphan), diphenhydramine (diphenhydramine), famotidine (famotidine), loperamide (loperamide), ranitidine (ranitidine), cimetidine (cimetidine), astemizole (astemidazole), fentezomib (fentezine), fenpyradine (phenazine), fentezine (fentezine), fentezine (fenteosine, fentezine), or a (fenteosine) or a.

In one aspect, the soft chew compositions of the present invention comprise carprofen as an active ingredient.

Carprofen is a nonsteroidal anti-inflammatory drug (NSAID) marketed worldwide under various brands. Veterinarians will typically prescribe carprofen to animals as an adjunct treatment for a variety of conditions. Carprofen is a particularly popular therapeutic agent for canine and equine administration. Carprofen provides a daily treatment for pain and inflammation caused by various joint pains, as well as postoperative pain. Carprofen reduces inflammation by inhibiting COX-1 and COX-2. The specificity of carprofen for COX-2 varies from species to species.

In one aspect, the soft chew compositions of the present invention comprise febantel as an active ingredient.

Febantel is an anthelmintic useful for repelling insects in animals and is particularly effective against roundworms and tapeworms. Febantel kills parasites by binding to tubulin subunits and interfering with microtubule formation.

In the horse, febantel is readily absorbed from the gastrointestinal tract and rapidly metabolized to fenbendazole sulfone, fenbendazole, and oxybenzazole. Febantel is also absorbed from the intestinal tract of cattle and sheep.

Febantel is also administered to companion animals. For example, in dogs and cats, commercially available(combination of febantel and praziquantel) is unlikely to cause serious side effects at typical doses.

In one aspect, the soft chewable compositions of the invention comprise 8- (3, 5-dichlorophenyl) -N- [ (4S) -3, 4-dihydro-2H-chromen-4-yl]-4- (dimethylamino) quinoline-3-carboxamide (empirical formula: C) ₂₇ H ₂₃ Cl ₂ N ₃ O ₂ ) As an active ingredient.

In one aspect, the soft chew compositions of the present invention comprise 2-chloro-N- (1-cyanocyclopropyl) -5- [2 ' -methyl-5 ' - (pentafluoroethyl) -4 ' - (trifluoromethyl) -2 ' H-1, 3 ' -dipyrazol-4-yl]Benzamide (empirical formula: C) ₂₁ H ₁₃ ClF ₈ N ₆ O) as an active ingredient.

In one aspect, the soft chew compositions of the present invention comprise a total amount of one or more active ingredients from 0.001% to 75%, or from 0.005% to 50%, or from 0.01% to 35%, or from 0.05% to 20%, or from 0.1% to 15%, or from 1% to 10%, by total weight of the soft chew composition.

In one aspect, the soft chew compositions of the present invention comprise a total amount of one or more active ingredients from 0.01mg to 100mg, or from 0.1mg to 75mg, or from 0.25mg to 50mg, or from 0.5mg to 25 mg.

By "disintegrant" is meant an ingredient, generally free of other active ingredients, which aids in comminuting the soft chewable composition of the present invention when administered to an animal.

In one aspect, the soft chewable composition of the invention may comprise any pharmaceutically acceptable disintegrant.

In another aspect, the soft chewable composition of the invention comprises one or more disintegrants selected from agar, potato or tapioca starch, corn starch, pregelatinized and modified starches, clays such as bentonite, various silicates, sodium starch glycolate, methylcellulose, croscarmellose sodium, microcrystalline cellulose (e.g., Avicel), sodium carbonate, calcium carbonate, low substituted hydroxypropyl cellulose, colloidal silicon dioxide, cellulose polacrilin potassium (e.g., Amberlite), guar, locust bean, karaya gum, xanthan gum, pectin, tragacanth gum, polyvinylpyrrolidone, crospovidone, rice, carboxymethylcellulose calcium, directly compressible mannitol, and croscarmellose sodium.

In certain embodiments, the soft chew compositions of the present invention do not comprise calcium carboxymethylcellulose, sodium carboxymethylcellulose, or hydroxypropylcellulose.

In another aspect, the soft chewable composition of the invention comprises one or more disintegrants selected from crospovidone, sodium starch glycolate, and/or croscarmellose sodium.

Crospovidone (also known as crospovidone N-pyrrolidone, or PVP) is a common inactive ingredient in pharmaceuticals and dietary supplements that allows for the absorption of active drugs. It is considered to be a synthetic povidone analogue. Chemically, crospovidone is an inert and insoluble white to yellowish free-flowing powder. It has hygroscopicity or water absorption and has good swelling characteristics. It is this swelling characteristic that makes them useful as disintegrants in pharmaceutical dosage forms. Crospovidone is not orally absorbed.

Sodium starch glycolate is the sodium salt of carboxymethyl ether. The glycolic acid starch is from rice, potato, wheat or corn. Sodium starch glycolate is a white to off-white, tasteless, odorless, relatively free-flowing powder used as a pharmaceutically acceptable dissolution excipient for tablet and capsule dosage forms. Sodium starch glycolate absorbs water rapidly, causing swelling, which in turn causes rapid disintegration of the tablets and granules.

Croscarmellose sodium is an internally cross-linked sodium carboxymethylcellulose that is used as a disintegrant in pharmaceutical formulations. Crosslinking reduces water solubility while still allowing the material to swell and absorb several times its weight in water. Thus, it provides excellent drug dissolution and disintegration properties, thereby improving bioavailability by allowing the active ingredient to better contact with body fluids.

In one aspect, the soft chew compositions of the present invention comprise a total amount of from 0% to 60%, or from 0.01% to 50%, or from 0.1% to 35%, or from 1% to 25% by weight of one or more disintegrants based on the total weight of the soft chew composition.

In certain embodiments, the soft chewable compositions of the present invention do not include a disintegrant. In one aspect, the soft chew compositions of the present invention that do not include a disintegrant still exhibit excellent disintegration rates.

In one aspect, the soft chew composition of the present invention disintegrates within 20 minutes, or within 15 minutes, or within 12 minutes, or within 8 minutes, or within 5 minutes after addition to water at 37 ℃.

In one aspect, the soft chew composition of the present invention disintegrates within 30 minutes, or within 25 minutes, or within 20 minutes, or within 15 minutes after one week of storage. In another aspect, the soft chew composition of the present invention disintegrates within 30 minutes, or within 25 minutes, or within 20 minutes, or within 15 minutes after one month of storage.

In one aspect, the formulation of the soft chew compositions of the present invention may be modified to achieve a desired palatability and/or a desired disintegration time.

"Binder or binding agent" means an ingredient that is generally not otherwise active, which increases the cohesiveness of the formulation to provide adhesion, to form an adhesive mass and to ensure a suitable compacted form. Binders are commonly used for direct compression and are described in Lieberman et al, Pharmaceutical Dosage Forms (Pharmaceutical Dosage Forms), 2 nd edition, volume 1, pages 209-214 (1990), and for soft chewable compositions prepared by an extrusion process.

In certain embodiments, the soft chew compositions of the present invention may comprise a binder. In one aspect, the pharmaceutically acceptable binder comprises: microcrystalline cellulose, hydroxypropyl methylcellulose, ethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP) (e.g., povidone (Kollidon 25, 30 and 90) and copovidone (Kollidon VA 64), polyethylene glycol, gum arabic, pregelatinized starch, sucrose, lactose (e.g., aqueous, anhydrous, monohydrate), xylitol, sorbitol, maltitol, corn starch, potato starch, and mixtures thereof.

In certain embodiments, the soft chew compositions of the present invention do not include any of microcrystalline cellulose, hydroxypropyl methylcellulose, ethyl cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinyl pyrrolidone (PVP), copovidone, corn starch, potato starch, pregelatinized starch, polyvinyl caprolactam, xylitol, sorbitol, or maltitol.

In certain embodiments, the soft chew compositions of the present invention do not comprise a binder.

In certain embodiments, the soft chew compositions of the present invention do not include a binder or disintegrant, or do not include either a binder or a disintegrant.

It has been found that the exclusion of inactive binders and/or disintegrants allows for the maximization of typical pharmaceutical ingredients where palatable components, rather than taste or smell, are not attractive to animals. Embodiments lacking a binder and/or disintegrant thus achieve high palatability, and thus animal compliance.

It has further been found that, unexpectedly, the embodiments lacking the binder still exhibit the desired cohesiveness.

It has further been found that, unexpectedly, the embodiments lacking a disintegrant exhibit excellent disintegration rates.

By "wetting agent" is meant an ingredient, generally otherwise inactive, that tends to attract and/or retain water in the pharmaceutical composition. Generally, the inclusion of a wetting agent increases the solubility of the active ingredient in the pharmaceutical or veterinary composition. The soft chewable compositions of the present invention may include any pharmaceutically acceptable wetting agent or agents.

In one aspect, the soft chew compositions of the present invention comprise one or more wetting agents selected from gums, waxes, e.g., paraffin, glycerin, glycerol, glyceryl stearate, glyceryl caproate, glyceryl monostearate, miglyol (e.g., miglyol 812, miglyol 840), maltitol, sorbitol, malic acid, cetyl alcohol, ethylene glycol, monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether, triethylene glycol monoethyl ether, diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, methanol, ethanol, isopropanol, methoxypropanol, diethylene glycol monobutyl ether, tetraethylene glycol, triethylene glycol, butyl diglycol, dimethylacetamide, dimethylformamide, n-methylformamide, dipropylene glycol n-butyl ether, diethylene glycol monobutyl ether acetate, diethylene glycol monoethyl ether acetate, monomethyl acetamide, glycerin, glyceryl caproate, glyceryl monostearate, miglyol (e.g., miglyol), miglyol 812, triethylene glycol monoethyl ether, methanol, ethanol, isopropanol, methoxypropanol, diethylene glycol monobutyl ether, tetraethylene glycol monobutyl ether, triethylene glycol, butyl diglycol, butyl glycol, butyl diglycol, butyl glycol, butyl diglycol acetate, and methyl acetamide, and/or a glycol acetate, 2-pyrrolidone and N-methylpyrrolidone, propylene glycol, methoxypropanol, various grades of polyethylene glycol ("PEG"), e.g., PEG6000, PEG4000, PEG3350, PEG2000, PEG1000 and/or PEG400, dipropylene glycol monomethyl ether, tetrahydrofurfuryl alcohol, Solutol HS15 (polyethylene glycol mono-and diesters of 12-hydroxystearic acid), glyceryl cocoate, methoxypolyethylene glycol, polypropylene glycol, polybutylene glycol, tetraethylene glycol, dipropylene glycol N-butyl ether, glyceryl caprylate/caprate, glyceryl caprylate, dibutyl adipate, liquid polyoxyethylene glycols, propylene carbonate, butylene carbonate, acetonide, xylene, dimethyl isosorbide, short, medium and long chain and aromatic fatty acids (e.g., butyric, capric, succinic, adipic, sebacic, caprylic, lauric, myristic, stearic acid, succinic acid, adipic acid, sebacic acid, caprylic, lauric acid, myristic acid, stearic acid, and mixtures thereof, Linoleic acid and benzoic acid), glycerol monooleate, glycerol ricinoleate, isopropyl myristate, ethyl oleate, ethyl laurate, propylene glycol monocaprylate, propylene glycol monolaurate, arachinate, dibutyl sebacate, triglycerides (such as castor oil, cottonseed oil, sesame oil, linseed oil, safflower oil, peanut oil, soybean oil, coconut oil, olive oil, corn oil, and almond oil), silicones, hyaluronic acid, honey, molasses, aloe vera, lecithin, panthenol, alginates, polysorbate 80, surfactants, emulsifiers, synthetic alcohols (e.g., hydroxystearate, myristate, oleate), sucrose, triacetin, water, and mineral oils.

In certain embodiments, the soft chew compositions of the present invention do not include any of miglyol, Solutol HS15 (polyethylene glycol mono-and diesters of 12-hydroxystearic acid), ethanol, or triglycerides (e.g., castor oil, cottonseed oil, sesame oil, safflower oil, peanut oil, soybean oil, coconut oil, and olive oil).

In another aspect, the soft chew compositions of the present invention comprise one or more wetting agents selected from the group consisting of honey, molasses, gum, gelatin, wax, paraffin, 2-pyrrolidone, water, oil, surfactants, emulsifiers, alginates, glycerin, polysorbate 80, glycerin, propylene glycol, various grades of polyethylene glycol ("PEG"), e.g., PEG6000, PEG4000, PEG3350, PEG2000, PEG1000, and/or PEG 400.

In one aspect, the soft chew compositions of the present invention comprise one or more humectants in an amount from 5% to 80%, or from 15% to 70%, or from 30% to 60%, by total weight of the soft chew composition.

"hardener (curing agent or plasticizer)" means an inactive ingredient that is not an adhesive, is solid or highly viscous at room temperature, and can generally be melted by heating and cured or made viscous at room temperature to provide a hardened structure. The soft chewable composition of the invention may optionally include any pharmaceutically acceptable hardening agent.

In one aspect, the soft chew compositions of the present invention comprise one or more hardening agents selected from the group consisting of microcrystalline cellulose, hydroxypropyl methylcellulose, ethylcellulose, polyvinylpyrrolidone, copovidone, acacia gum, tragacanth gum, gelatin, sucrose, lactose (e.g., aqueous, anhydrous, monohydrate), xylitol, sorbitol, maltitol, corn starch, potato starch, alginates, waxes, solid lipids, and various grades of polyethylene glycol ("PEG"), e.g., PEG6000, PEG4000, PEG3350, PEG2000, PEG1000 (e.g., PEG1000 or generally higher).

In another aspect, the soft chew compositions of the present invention include one or more stiffening agents that also act as wetting agents selected from waxes, solid lipids and various grades of polyethylene glycol ("PEG"), e.g., PEG6000, PEG4000, PEG3350, PEG2000 and/or PEG1000 (e.g., PEG1000 or generally higher).

In certain embodiments, the soft chew compositions of the present invention do not include a hardening agent, which may also act as a binder, for example, microcrystalline cellulose, hydroxypropyl methylcellulose, ethylcellulose, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), copovidone, corn starch, potato starch, pregelatinized starch, polyvinyl caprolactam, xylitol, sorbitol, maltitol.

In certain embodiments, the soft chew compositions of the present invention do not include microcrystalline cellulose, hydroxypropyl methylcellulose, ethyl cellulose, polyvinylpyrrolidone, copovidone.

In one aspect, the soft chew compositions of the present invention comprise one or more hardening agents in an amount from 1% to 75%, or from 5% to 50%, or from 10% to 30%, by total weight of the soft chew composition.

In one aspect, the soft chewable composition of the invention may comprise one or more pharmaceutically acceptable solvents, such as N-methyl-2-pyrrolidone or dimethyl sulfoxide (DMSO).

In one embodiment, the soft chewable composition of the invention contains starch.

In another embodiment, the soft chew compositions of the present invention do not contain starch as a binder.

In yet another embodiment, the soft chew compositions of the present invention do not contain any starch.

In one aspect, the total weight of the soft chew composition of the present invention may be from 5mg to 2kg, or from 10mg to 1kg, or from 20mg to 500g, or from 30mg to 100g, or from 50mg to 50g, or from 100mg to 20g, or from 250mg to 10 g.

In one aspect, the present disclosure provides a soft chew composition comprising water. In one aspect, the soft chew compositions of the present invention may comprise from 0% to 20% water, or from 0.0001% to 10% water, or from 0.001% to 5% water, or from 0.01% to 2% water, by total weight of the soft chew composition.

In another aspect, the present disclosure further provides soft chew compositions that are substantially free of water.

The soft chew compositions of the present invention have a softness that is particularly desirable for animal subjects and results in excellent compliance by animal subjects to whom the compositions are administered.

In one aspect, the soft chew compositions of the present invention exhibit a hardness of from 0.001 to 100N, or from 0.001N to 75N, or from 0.005N to 50N, or from 0.01 to 20N, or from 0.1 to 15N.

In certain embodiments, the soft chew compositions of the present invention exhibit excellent shelf life and remain soft for long periods of time after manufacture and are desirable for test animals. Soft chews that do not exhibit sustained softness may become brittle and thus less palatable to the animal over time. Thus, the compositions of the present invention may remain desirable for animal subjects for extended periods of time, and thus reduce costs by not requiring frequent replacement.

As used herein, the term "treatment" and grammatical variations thereof means subjecting an animal subject to a regimen, therapy, procedure or treatment in which a physiological response or result is desired in the subject. In particular, the methods and compositions of the invention can be used to slow the development of disease symptoms or delay the onset of a disease or condition or halt the progression of disease development. However, because each treated animal subject may not respond to a particular treatment regimen, therapy, procedure, or treatment, treatment need not achieve the desired physiological response or result in each subject or subject population. Thus, a given subject or test population may not respond or respond adequately to treatment.

As used herein, the term "ameliorating" and grammatical variants thereof means reducing the severity of a disease symptom in a subject.

As used herein, the term "preventing" and grammatical variations thereof means that a compound or composition of the present invention is administered to a subject animal that, at the time of administration, is not diagnosed as having a disease or condition but is expected to develop into or be at increased risk of a disease or condition. Prevention also comprises administering at least one compound or composition of the invention to those subjects deemed to be predisposed to the disease or condition due to age, family history, genetic or chromosomal abnormalities, due to the presence of one or more biomarkers for the disease or condition, and/or due to environmental factors.

In one aspect, the present disclosure provides a method of treating an animal comprising administering to the animal a soft chew composition described herein.

In one aspect, the soft chew composition may be administered to an animal once, twice, three times, four times, five times, six times, seven times, eight times, nine times, or ten times per day depending on the dose, severity of the disease or condition, and the particular animal species and size.

In one aspect, the soft chew composition may be administered in a dosage of one, two, three, four, five, six, seven, eight, nine, or ten soft chew tablets depending on the severity of the disease or condition and the particular animal species and size.

In one aspect, the soft chew composition may be administered to an animal.

In one aspect, the animal to be treated is a dog, cat, horse, pig, sheep, goat, cow, rabbit, llama, deer, elk, or poultry.

In another aspect, the animal to be treated is a dog, cat, or horse.

The soft chewable compositions of the present invention may optionally contain additional ingredients and/or materials commonly used in such veterinary compositions. In other embodiments, optional ingredients are not present. These ingredients and materials are well known in the art and include (1) fillers or extenders such as starch, lactose, sucrose, glucose, mannitol, and silicic acid; (2) solution retarders, such as paraffin; (3) absorption promoters, such as quaternary ammonium compounds; (4) lubricants, such as sodium oleate, sodium stearate, calcium stearate, zinc stearate, magnesium stearate, polyethylene glycol, talc, mineral oil, stearic acid, sodium benzoate, sodium acetate, sodium chloride and sodium lauryl sulfate; (5) suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth; (6) buffering agents such as potassium metaphosphate, potassium phosphate, sodium monoacetate, and sodium citrate anhydrous and dihydrate; (7) excipients, such as lactose, milk sugar, polyethylene glycol, animal and vegetable fats, oils, waxes, paraffin, cacao butter, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicic acid, talc, salicylate, zinc oxide, aluminum hydroxide, calcium silicate and polyamide powder; (8) inert diluents, such as dibasic calcium phosphate, kaolin, lactose, dextrose, magnesium carbonate, sucrose, mannitol, microcrystalline cellulose, powdered cellulose, precipitated calcium carbonate, calcium sulfate, sorbitol, starch, and water or other solvents; (9) preservatives, such as paraben, alcohol, antimicrobial agents, benzoic acid, sodium benzoate, benzyl alcohol, sorbic acid, parabens and isopropyl alcohol; (10) a surfactant; (11) dispersing agents, such as synthetic and natural gums, including tragacanth, acacia, alginate, dextran, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone and gelatin; (12) controlled release or absorption delaying agents such as hydroxypropylmethyl cellulose, other polymer matrices, biodegradable polymers, liposomes, microspheres, aluminum monostearate, gelatin, and waxes; (13) an opacifying agent; (14) an adjuvant; (15) emulsifying and suspending agents; (16) solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butylene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan; (17) antioxidants such as ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, hypophosphorous acid, monothioglycerol, propyl gallate, sodium ascorbate, sodium bisulfite, sodium formaldehyde sulfoxylate, and sodium metabisulfite; (18) agents that make the formulation isotonic with the blood of the intended recipient, such as sugars and sodium chloride; (19) a thickener; (20) coating materials, such as lecithin; and (21) sweeteners, colorants, fragrances and preservatives.

Each such ingredient or material must be pharmaceutically acceptable, i.e., compatible with the other ingredients of the formulation and not deleterious to the animal being tested.

The soft chewable compositions of the present invention may be made by any method, such as by blending and extrusion, blending and tapping, injection molding, tableting, and other methods.

The following examples are illustrative of certain aspects of the disclosure and are not intended to limit the disclosure.

Examples of the invention

Example 1 exemplary Soft chew formulation

Table 1.1 illustrates a non-comprehensive selection of components of exemplary soft chew compositions of the present invention, including sweet potato flour or liver flavoring agents.

The amounts of the ingredients are given in w/w% based on the total weight of the soft chew composition. The active ingredient is indicated in parentheses and is carprofen, febantel or 8- (3, 5-dichlorophenyl) -N- [ (4S) -3, 4-dihydro-2H-chromen-4-yl]-4- (dimethylamino) quinoline-3-carboxamide (empirical formula: C) ₂₇ H ₂₃ Cl ₂ N ₃ O ₂ ) Any one of (1) to (2)It is an early anti-heartworm active substance.

Table 1.1: exemplary compositions

Table 1.2 illustrates a non-comprehensive selection of components of exemplary soft chew compositions of the present invention that include blueberry powder as a flavoring agent.

The amount of the ingredients is given in w/w% based on the total weight of the soft chew composition.

Table 1.2: exemplary compositions including blueberry powder

Example 2 hardness and disintegration after storage

Formulations example 1 and example 2 were each stored for one month.

After one week, the soft chew compositions of each of formulation examples 1 and 2 were analyzed and their hardness values and disintegration times were recorded.

Likewise, after one month, the soft chew compositions of each of formulation examples 1 and 2 were analyzed and their hardness values and disintegration times were again recorded.

Table 2 illustrates the hardness values and disintegration times observed at 0 days, 7 days and one month after manufacture.

Table 2: hardness and disintegration after storage

Example 3-further exemplary Soft chew formulation

The exemplary formulation example 3 set forth in table 1 above was slightly modified to include water (i.e., formulation example 3.1) and was further modified to employ a different active ingredient (i.e., formulation example 3.2).

Table 3 illustrates further exemplary soft chew formulations of the present invention. In addition to the ingredients listed in tables 1.1 and 1.2 above, the exemplary soft chew formulations of table 3, i.e., example 6, example 7, example 8, and example 9, may further include a liquid liver flavoring agent, PEG2000, PEG3350, NMP (-P61)/2-pyrrolidone, and the active ingredient 2-chloro-N- (1-cyanocyclopropyl) -5- [2 ' -methyl-5 ' - (pentafluoroethyl) -4 ' - (trifluoromethyl) -2 ' H-1, 3 ' -bispyrazol-4-yl]Benzamide (empirical formula: C) ₂₁ H ₁₃ ClF ₈ N ₆ O). Table 3 sets forth illustrative formulations example 3, example 3.1, and example 3.2 for comparison.

Table 3: further exemplary Soft chew formulations

Example 4 intermolecular comparison on the day of production

Table 4 illustrates the hardness values (N) and disintegration times (minutes) for exemplary soft chew formulations example 0, example 2, example 3.1, and example 3.2 on the same day (i.e., "day 0") the soft chew composition was made.

Table 4: making the day's intermolecular comparisons

	Active ingredient	Hardness at day 0, N	Disintegration time on day 0, min
				Example 0	Placebo	15.9	7.5
Example 2	Febantel	15.3	4.5
				Example 3.1	C 21 H 13 ClF s N 6 O	11.3	12.0
Example 3.2	C 27 H 23 Cl 2 N 3 O 2	12.2	14.5

Formulation example 2 exhibited rapid disintegration compared to examples 3.1 and 3.2. Formulation example 2 contains no water.

Unexpectedly, formulation example 3 exhibited significantly lower hardness than example 0, example 2, and even example 3.1 and example 3.2. As described above, examples 3.1 and 3.2 exhibited reduced hardness compared to example 3 due to the addition of water. Thus, it can be concluded that the particular choice of active ingredient significantly affects the hardness and disintegration of the soft chewable composition.

Example 5 —Acceptance of placebo Soft chews

Table 5 illustrates additional placebo formulations used to study voluntary food compliance for 15 breeding dogs, including dogs ranging from pet dogs to large dogs.

The dogs were given each of the placebo formulations in table 5 once daily for three consecutive days.

Each of the four placebo formulations set forth below exhibited excellent palatability.

Table 5: acceptability after administration to dogs

Thus, all tested placebo formulation examples 10 and 11 were received at a high rate in the animal subjects administered the placebo formulation.

Example 6-further exemplary Soft chew formulation

Table 6 illustrates additional exemplary formulations of the soft chew compositions of the present invention.

Table 6: further exemplary Soft chew formulations

Notably, the formulations set forth in table 6 were able to carry high odorant loadings, and in the case of example 13, high drug loadings as well.

Example 7-further exemplary Soft chew formulation

Table 7 illustrates additional exemplary formulations of the soft chew compositions of the present invention.

Table 7: further exemplary Soft chew formulations

Example 8-further exemplary Soft chew formulation

Table 8 illustrates additional exemplary formulations of the soft chew compositions of the present invention.

Table 8: further exemplary Soft chew formulations

Example 9 further exemplary Soft chew formulation

Table 9 sets forth additional exemplary formulations of the soft chew compositions of the present invention.

Table 9: further exemplary Soft chew formulations

The soft chew compositions of table 9 do not include any disintegrant, but still exhibit excellent disintegration times of between only 6 and 11 minutes.

Example 10-further exemplary Soft chew formulation

Table 10 illustrates additional exemplary formulations of the soft chew compositions of the present invention.

Table 10: further exemplary Soft chew formulations

The soft chew compositions of table 10 do not include any disintegrant, but still exhibit excellent disintegration times of between only 4 and 10.8 minutes.

Further, the soft chew compositions of table 10 are capable of carrying a high flavor loading of between 49.6% and 57.9% of the total weight of the composition.

Example 11-further exemplary Soft chew formulation

Table 11 illustrates additional exemplary formulations of the soft chew compositions of the present invention.

Table 11: further exemplary Soft chew formulations

The soft chew compositions of table 11 exhibit excellent disintegration times of between only 5.8 and 13 minutes.

In addition, the soft chew compositions of table 11 are capable of carrying a high flavor potentiator loading of 56% of the total weight of the composition.

Example 12-further exemplary Soft chew formulation

Table 12 sets forth additional exemplary formulations of the soft chew compositions of the present invention.

Table 12: further exemplary Soft chew formulations

The soft chew compositions of table 12 exhibit excellent disintegration times of only 4.5 minutes.

In addition, the soft chew compositions of table 12 are capable of carrying high flavor enhancer loadings of up to 55.3% of the total weight of the composition.

Example 13 further exemplary Soft chew formulation

Table 13 illustrates additional exemplary formulations of the soft chew compositions of the present invention.

Table 13: further exemplary Soft chew formulations

The soft chew compositions of table 13 exhibit excellent disintegration times of between only 14.5 and 15 minutes.

Furthermore, the soft chew compositions of table 13 are capable of carrying as much as a high flavor potentiator loading of between 41% and 48% of the total weight of the composition.

Example 14-further exemplary Soft chew formulation

Table 14 sets forth additional exemplary formulations of the soft chew compositions of the present invention.

Table 14: further exemplary Soft chew formulations

Composition (I)	Example 36
		Liver powder	5.0
Sweet potato powder	42.3
		Cross-linked polyvidone	5.0
PEG1000	20.0
		Glycerol	20.0
Water (W)	1.0
		C 21 H 13 ClF 8 N 6 O	6.7

Claims (21)

1. A soft chewable composition comprises

(a) At least one odorant;

(b) at least one wetting agent; and

(c) at least one active ingredient.

2. The soft chew composition of claim 1 further comprising

(d) And (3) water.

3. The soft chew composition of claim 1 or 2 wherein the (a) at least one flavor enhancer is selected from the group consisting of: apple powder, bean powder, beet powder, pepper powder, blueberry powder, broccoli powder, squash powder, cabbage powder, carrot powder, cauliflower powder, celery powder, carrot powder, chive powder, corn powder, cranberry powder, dill powder, kale powder, leek powder, lemon powder, mushroom powder, onion powder, orange powder, potato powder, pea powder, pumpkin powder, onion powder, spinach powder, tomato powder, mucic acid pulp powder, sweet potato powder, pumpkin powder, natural and artificial meat powder such as liver powder and artificial beef, yeast, cassava syrup, honey and salt.

4. The soft chew composition of any of claims 1 to 3 wherein the (b) at least one humectant is selected from the group consisting of: glycerol, glycerol monostearate, maltitol, sorbitol, malic acid, cetyl alcohol, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether, diethylene glycol monomethyl ether, methanol, ethanol, isopropanol, methoxypropanol, diethylene glycol monobutyl ether, tetraethylene glycol, triethylene glycol, butyl diglycol, dimethylacetamide, dimethylformamide, n-methylformamide, dipropylene glycol n-butyl ether, propylene glycol, PEG6000, PEG4000, PEG3350, PEG2000, PEG1000, PEG400 and mineral oil.

5. The soft chew composition of any of claims 1 to 4 further comprising (e) at least one hardening agent selected from the group consisting of: microcrystalline cellulose, hydroxypropyl methylcellulose, ethylcellulose, polyvinylpyrrolidone, copovidone, acacia gum, tragacanth gum, gelatin, sucrose, lactose, xylitol, sorbitol, maltitol, corn starch, potato starch, alginates, waxes, solid lipids, PEG6000, PEG4000, PEG3350, PEG2000, PEG1000, and PEG 400.

6. The soft chewable composition of any one of claims 1 to 5, further comprising (f) at least one disintegrant selected from the group consisting of: agar, potato starch, tapioca starch, corn starch, pregelatinized and modified starches, clays, alginates, alginic acid, silicates, sodium starch glycolate, methylcellulose, croscarmellose sodium, microcrystalline cellulose, sodium carbonate, calcium carbonate, low-substituted hydroxypropylcellulose, colloidal silicon dioxide, cellulose polacrilin potassium, gums, guar, locust bean, karaya gum, xanthan gum, pectin, tragacanth gum, polyvinylpyrrolidone, crospovidone, carboxymethylcellulose calcium, directly compressible mannitol, and croscarmellose sodium.

7. The soft chewable composition of any one of claims 1 to 6, wherein the (c) at least one active ingredient is selected from the group consisting of: antiparasitic, acaricidal, anthelmintic, insecticidal, antimicrobial, antiviral, antibacterial, anti-inflammatory, psychotherapeutic, proton pump inhibitor, analgesic, antiallergic, and antihypertensive agents.

8. The soft chew composition of any of claims 1 to 7 wherein the (a) at least one flavoring agent is present in an amount of 1% to 90% by total weight of the soft chew composition.

9. The soft chew composition of any of claims 1 to 8 wherein the (b) at least one humectant is present in an amount of 5% to 80% by total weight of the soft chew composition.

10. The soft chew composition of any of claims 5 to 9 wherein the (e) at least one hardening agent is present in an amount of 1% to 75% by total weight of the soft chew composition.

11. The soft chewable composition of any one of claims 6 to 10, wherein the (f) at least one disintegrant is present in an amount of from 0.01% to 50% by total weight of the soft chewable composition.

12. The soft chew composition of any of claims 1 to 11 wherein the (c) at least one active ingredient is present in an amount up to 25% by total weight of the soft chew composition.

13. The soft chewable composition according to any one of claims 1 to 12, wherein the (c) at least one active ingredient is present in an amount of from 0.01mg to 100 mg.

14. The soft chew composition of any of claims 1 to 13 wherein the total weight of the soft chew composition is from 10mg to 1,000 mg.

15. The soft chew composition of any of claims 1 to 13 wherein the soft chew composition exhibits a hardness of no more than 35N.

16. The soft chew composition of any of claims 1 to 15 wherein the soft chew composition disintegrates within 20 minutes.

17. The soft chew composition of any of claims 2 to 16 wherein the soft chew composition comprises (f) water in an amount of up to 10% by total weight of the soft chew composition.

18. The soft chew composition of any of claims 2 to 17 wherein the soft chew composition is made by a tablet press.

19. A method of treating an animal having a disease or condition comprising administering to the animal the soft chew composition of any one of claims 1 to 18, wherein the disease or condition is inflammation or a parasite.

20. The method of claim 18, wherein the animal is a dog, cat, horse, pig, llama, rabbit, goat, sheep, deer, elk, cow, or poultry.

21. Use of the soft chew composition of any of claims 2 to 16 for the treatment of an animal.