Animal food composition comprising source of glycyrrhizin

Abstract

The present disclosure relates to an animal food composition comprising a source of glycyrrhizin for use in the prevention and / or treatment of allergic inflammatory skin diseases wherein the animal food composition is formulated to provide glycyrrhizin to the animal in an amount of at least about 0.02 mg / kg body weight per day.

Description

[0001] 1. Cross-reference to related applications

[0002] This application claims the benefit of priority of European Patent Application No. 22170352.3 filed on April 27, 2022, the contents of which are incorporated herein by reference in their entirety. 2. Technical field

[0003] The presently disclosed subject matter relates to the field of animal food compositions for preventing and / or treating allergic inflammatory skin diseases, in particular for preventing and / or treating atopic dermatitis. 3. Background technology

[0004] Reports strongly suggest that the incidence of allergic diseases is increasing, especially in Western societies (Pawankar et al., World Allergy Organization. (2013) 11-9).

[0005] Allergic inflammatory skin diseases are chronic diseases characterized by clinical symptoms such as erythema, pain, redness, swelling, and the appearance of small blisters or papules on the skin. They are the second most common allergic skin disease in animals, especially dogs, second only to flea allergies. These allergic reactions can be caused by usually harmless substances such as grasses, mold spores, house dust mites and other environmental allergens.

[0006] The main symptoms are skin inflammation and itching, often associated with scratching and excoriation in affected animals, which is caused by an interaction of genetic and environmental factors. Allergic symptoms manifest as eczematous skin, and animals with atopic dermatitis (e.g. dogs) often experience itching or intense itching, hair loss, excoriation from deep scratching, frequent licking of the paws, and excessive tear secretion. Secondary skin problems are also common, including skin infections and excessive sebum secretion. In particular, atopic dermatitis is one of the most common allergic inflammatory skin diseases.

[0007] A common feature of these diseases in their various manifestations is the bias of the immune response toward the expression of so-called T-helper 2 (Th-2) cytokines, i.e., inflammatory mediators associated with the promotion of IgE and eosinophil responses. For example, an increase in the interleukins IL-4 or IL-5 relative to Th-1 helper cell cytokines such as interferon-γ (IFN-γ) or Th-17 helper cell cytokines such as IL-17 appears to skew the immune response toward an allergic phenotype. On the other hand, it is known that the Th-1 cytokine IFN-γ can inhibit IgE synthesis, Th-2 cell proliferation and IL-4 receptor expression on T cells (Spergel et al., Am J Clin Derm. 9 (2008) 233-234, Laurence et al., Natural Immunology. 8 (2007) 903-905, and Okamoto et al., Clinical and Experimental Immunology. 157 (2009) 27-34). Therefore, bioactive substances that modulate immune responses to inhibit Th-2 and even promote Th-1 cell proliferation and cytokine production may prove useful for treating allergic reactions or allergic diseases.

[0008] Several approaches to treating atopic dermatitis and pruritus have been described, including the use of ultramicronized palmitoylethanolamine (Noli et al.; Vet Dermatol 2015;26, 432-40) or antihistamines, such as fexofenadine, or drugs, such as cyclosporine. However, most of the available drugs are not suitable for long-term use due to significant side effects (and in many cases high costs). Although immunotherapy can improve symptoms when the allergen is identified, success rates remain variable. The ability to reduce reliance on medications would be seen as a valuable contribution to the field and a major goal of nutritional intervention.

[0009] Indeed, there is now evidence that genetic susceptibility can influence the immune system as well as functional / structural aspects of the skin barrier. Known environmental components include the allergen load and the microbial population present on the skin. Medications currently prescribed for allergic disease target individual aspects of disease ‘progression’, often immune related, but only manage the disease rather than provide long term remission or cure. Nutritional management strategies are more likely to be successful if they target multiple aspects simultaneously.

[0010] Many natural products derived from plant sources have shown potential for immunomodulatory effects (Block et al., Integrative Cancer Therapies. 2 (2003) 247-267, Gertsch et al., Journal of Ethnopharmacology. 136 (2011) 385-391 and Licciardi et al., Int Immunopharmacol. 11 (2011) 390-398). Some of these phytochemicals are purported to modulate immune pathways associated with allergic disease. However, the level of scientific support for these beneficial activities is mixed, and in some cases there is little support beyond the documented traditional uses.

[0011] In particular, attention has been paid to the root of Glycyrrhiza glabra, which has previously shown immunomodulatory properties. In fact, studies have shown that glycyrrhizin (also known as glycyrrhizic acid), an important chemical component of licorice, affects the maturation and signaling activity of dendritic cells (Bordbar et al., Immunopharmacol Immunotoxicol. 36 (2014) 52-60, Kim et al., Immunopharmacol Immunotoxicol. 35 (2013) 329-35 and Aipire et al., Sci Rep. 7 (2017) 43796 (Bordbar et al., Immunopharmacol Immunotoxicol. 36 (2014) 52-60, Kim et al., Immunopharmacol Immunotoxicol. 35 (2013) 329-35 and Aipire et al., Sci Rep. 7 (2017) 43796). Rep.7(2017)43796)), inhibiting certain Th-2 responses while tending towards Th-1 responses (Bordbar et al., Cell Immunol. 280(2012)44-49 and Hua et al., Int Immunopharmacol. 12(2012)518-25). In addition to glycyrrhizin, other important components in licorice, namely isoliquiritigenin and naringenin, have been shown to affect the induction and function of regulatory T cells (Guo et al., Sci Rep. 5(2015)14046).

[0012] Therefore, glycyrrhizin has been added to animal food compositions in the past to prevent and / or treat allergic inflammatory diseases: for example, WO2021 / 003280 describes the use of a composition of (i) a glycyrrhizin source and (ii) one or more sources of curcuminoids in an animal for this purpose, the disclosure of which is incorporated herein in its entirety.

[0013] However, the amount of glycyrrhizin that can be included in animal food compositions is usually very low. In fact, it has been previously shown that there is a correlation between the intake of glycyrrhizin and hypertension in dogs. Therefore, the official safety recommendation for glycyrrhizin is that the presumed safe intake (PSI), especially for dogs, is 1 mg / kg comprehensive feed, estimating 0.3 mg / day or 0.02 mg / kg body weight (Bwt) (Bwt / day) ("European Food Safety Authority Journal", 2015 recommendations based on the study by van Gelderen et al., Glycyrrhizic acid: the assessment of a no effect level, "Human & Experimental Toxicology" 2000, 19, 434-439 (EFSA Journal, 2015recommendations based on the study by van Gelderen et al., Glycyrrhizic acid: the assessment of a no effect level, Human & Experimental Toxicology, 2000, 19, 434-439)).

[0014] Therefore, the amount of active compounds contained in the composition and which can therefore provide the sought anti-inflammatory properties is limited. Therefore, there is still a need for treatment options for allergic inflammatory skin diseases (such as atopic dermatitis). There is also a need for alternative natural products for the treatment or prevention of such diseases. Therefore, there is still a need for new diets designed to improve immune function and barrier defense.

[0015] Furthermore, there remains a need for new treatment options for allergic inflammatory skin diseases such as atopic dermatitis, particularly new diets that are specifically effective for the disease and yet safe for the individuals being treated and have limited side effects. 4. Summary of the invention

[0016] Objects and advantages of the disclosed subject matter will be set forth in and will be obvious from the following description, and will also be learned by practice of the disclosed subject matter.

[0017] A first aspect of the present disclosure relates to an animal food composition comprising a source of glycyrrhizin for use in a method of preventing and / or treating inflammatory diseases or disorders, allergic inflammatory skin diseases, wherein the animal food composition is formulated to provide the animal with a daily amount of at least about 0.02 mg / kg body weight of glycyrrhizin.

[0018] In particular, the animal food composition can be formulated to provide the animal with a daily amount of about 0.02 mg / kg body weight to about 2 mg / kg body weight of glycyrrhizin.

[0019] In particular, the animal food composition can be formulated to provide the animal with a daily amount of about 0.03 mg / kg body weight to about 2 mg / kg body weight, particularly about 0.05 mg / kg body weight to about 1 mg / kg body weight, particularly about 0.1 mg / kg body weight to about 0.8 mg / kg body weight, particularly about 0.2 mg / kg body weight to about 0.6 mg / kg body weight of glycyrrhizin.

[0020] The present disclosure also relates to an animal food composition comprising a source of glycyrrhizin for use as a medicament, wherein the animal food composition is formulated to provide a daily amount of at least about 0.02 mg / kg body weight of glycyrrhizin to the animal.

[0021] In a specific embodiment, the animal food composition is selected from the group consisting of a nutritionally complete animal food composition, a food supplement, and a covering composition.

[0022] In a specific embodiment, the source of glycyrrhizin of the animal food composition comprises licorice root extract.

[0023] In a specific embodiment, the animal food composition further comprises linoleic acid.

[0024] In a specific embodiment, the animal food composition further comprises EPA / DHA (eicosapentaenoic acid / docosahexaenoic acid), taurine, lutein, vitamin E, and / or combinations thereof.

[0025] In a specific embodiment, the allergic inflammatory skin disease is selected from the group consisting of atopic dermatitis, flea allergic dermatitis, urticaria, insect bite allergy, angioedema, inhalant allergy, inhalant allergic dermatitis, food allergic dermatitis, contact dermatitis, miliary dermatitis, eosinophilic granuloma, head and neck pruritus and generalized pruritus.

[0026] A second aspect of the present disclosure relates to a kit comprising:

[0027] (i) a first part comprising a glycyrrhizin source; and

[0028] (ii) a second part comprising one or more additional ingredients;

[0029] A method for preventing and / or treating inflammatory diseases or disorders, allergic inflammatory skin diseases, wherein the kit is formulated to provide a daily amount of at least about 0.02 mg / kg body weight of glycyrrhizin to an animal.

[0030] A third aspect of the present disclosure is directed to an animal food composition comprising a source of glycyrrhizin, wherein the amount of glycyrrhizin is at least about 5 mg / kg based on the total weight of dry matter of the animal food composition.

[0031] In particular, the amount of glycyrrhizin may be from about 5 mg / kg to about 100 mg / kg based on the total weight of dry matter of the animal food composition.

[0032] In particular, the amount of glycyrrhizin can be about 5 mg / kg to 100 mg / kg, particularly about 10 mg / kg to about 75 mg / kg, particularly about 15 mg / kg to about 50 mg / kg, and particularly about 20 mg / kg to 45 mg / kg, based on the total weight of the dry matter of the animal food composition.

[0033] In a specific embodiment, the animal food composition comprises kibble and / or the animal food composition further comprises a protein source.

[0034] In particular, the animal food compositions include nutritionally complete food compositions.

[0035] In particular, the animal food composition or kit is formulated for oral administration.

[0036] In particular, the source of glycyrrhizin in the animal food composition or kit comprises licorice root extract.

[0037] In particular, the animal food composition may comprise one or more additional ingredients.

[0038] In particular, the one or more additional ingredients of the animal food composition or kit may be selected from linoleic acid, EPA / DHA, taurine, lutein, vitamin E and / or combinations thereof.

[0039] The above has basically outlined the features and technical advantages of the present application so that the following specific embodiments can be better understood.

[0040] The following will describe the additional features and advantages of the present application, which constitute the subject matter of the claims of the present application. It will be appreciated by those skilled in the art that the disclosed concepts and specific embodiments can be easily used as the basis for modifying or designing other structures for achieving the same purpose of the present application. It will also be appreciated by those skilled in the art that such equivalent constructions do not depart from the spirit and scope of the present application as set forth in the appended claims. Through the following description, the novel features unique to the present application in terms of organization and method of operation, as well as other purposes and advantages will be better understood. 5. Description of the drawings

[0041] Figure 1 The viability of Jurkat cells and human peripheral blood mononuclear cells (PBMCs) in the presence of increasing concentrations of licorice root extract (LRE) is shown. Cell viability was assessed by trypan blue exclusion. Data for both assays are expressed as cell viability relative to a positive control (+vecontrol) stimulated with anti-CD3 / CD28 alone (hollow diamonds "◇": viability of PBMCs; solid circles "●": viability of Jurkat cells) (mean + / - SEM). * indicates a statistically significant decrease in cell viability (P < 0.01). Based on these assays, a LRE concentration of 100 mg / ml was selected as the critical point for interpreting cytokine assays. * indicates a LRE concentration at which cell viability was reduced in Jurkat and PBMC populations (p < 0.01).

[0042] Figure 2 Represents human T cell (PBMC) proliferation and interleukin 2 (IL-2) release. Cell proliferation was induced by anti-CD3 / CD28 stimulation combination (solid circles "●": average cell proliferation) and assessed by incorporating [3H] thymidine into proliferating T cells. Interleukin-2 release from activated cells was measured by ELISA (hollow diamonds "◇": average IL-2 release) and displayed on the same coordinate axis. In both cases, the data are expressed as activity relative to the positive control (+vecontrol) activated alone (mean + / - SEM). Licorice extract had little effect on T cell proliferation or IL-2 release at concentrations previously shown to be non-cytotoxic (<100 mg / ml). There is evidence that it has an effect on cell proliferation at a concentration of 100 mg / ml. * indicates a LRE concentration at which IL-2 expression was significantly reduced (p<0.05); # indicates a LRE concentration at which cell proliferation was significantly reduced (p<0.05).

[0043] Figure 3The effect of licorice root extract on the release of IFN-γ (open square "□"), interleukin-17 (open circle "○") and interleukin-5 (open triangle "△") by anti-CD3 / CD28 activated human T cells is shown. The data are expressed as the cytokine concentration (mean + / - SEM) relative to the positive control (+ve control) activated alone. * indicates the concentration of licorice extract that significantly inhibits the release of IL-5 alone; # indicates the concentration of licorice extract that significantly inhibits the release of all 3 cytokines (p<0.05). 6. Specific implementation methods

[0044] The subject matter of the present disclosure relates to providing a product for preventing and / or treating inflammatory diseases or conditions, allergic inflammatory skin diseases (especially atopic dermatitis, i.e. canine atopic dermatitis) in animals (especially dogs). In particular, the product can be used to support the treatment of canine atopic dermatitis.

[0045] The disclosed subject matter herein provides an animal food composition comprising an amount of a glycyrrhizin source above the recommended daily dose.

[0046] Surprisingly, the presently disclosed subject matter has determined that an aqueous extract of licorice root can inhibit the release of interleukin 5 (IL-5) from activated T cells within a concentration range that is non-cytotoxic and does not stimulate proliferation or interleukin 2 (IL-2) release. In addition, the presently disclosed subject matter was able to demonstrate that consumption of glycyrrhizin in an amount greater than about 20 times the recommended daily dose for dogs does not cause any significant blood pressure homeostasis in adult dogs. In addition, the presently disclosed subject matter has shown that consumption of glycyrrhizin in an amount greater than about 20 times the recommended daily dose for dogs does not cause any changes in potassium excretion and aldosterone secretion, a result that suggests that such high doses of glycyrrhizin do not affect renal function.

[0047] Therefore, the subject matter of the present disclosure relates to an animal food composition comprising a glycyrrhizin source that can be provided to an animal (particularly a canine, such as a dog) in an amount higher than the generally recommended amount, while the food composition is still safe, i.e., does not cause an increase in blood pressure, nor does it affect renal function, such as not causing an increase in potassium excretion or an increase in aldosterone secretion. This composition can be used to prevent and / or treat inflammatory diseases or conditions, allergic inflammatory skin diseases, and more particularly, for animals suffering from atopic dermatitis. In a specific embodiment, the animal is a canine. In certain embodiments, the canine is a dog.

[0048] As used herein, inflammatory diseases or disorders include gastrointestinal inflammation.

[0049] Additionally, the presently disclosed subject matter provides an animal food composition that exhibits good overall palatability and digestibility, particularly to dogs, and that remains stable throughout the manufacturing process.

[0050] More particularly, the subject matter of the present disclosure also provides an animal food composition, which can include a food supplement, a covering composition and / or a complete food composition. The animal food composition disclosed herein consists of a food supplement or a complete food composition, comprising a glycyrrhizin source in an amount specified herein. In some embodiments, the food composition is in the form of a wet food composition, such as a gravy composition. Alternatively, the food composition is in the form of a dry food composition, such as a kibble.

[0051] For the sake of clarity and not limitation, the detailed description of the presently disclosed subject matter is divided into the following subsections:

[0052] 6.1. Definitions

[0053] 6.2. Animal food compositions;

[0054] 6.3. Methods of preparing animal food compositions; and

[0055] 6.4. Therapeutic applications.

[0056] 6.1. Definitions

[0057] The terms used in this specification generally have their ordinary meanings in the art in the context of the present disclosure and in the specific context in which each term is used. Certain terms are discussed below or elsewhere in this specification to provide additional guidance to professionals when describing the methods and compositions of the present invention and how to make and use them.

[0058] For the purpose of interpreting this specification, the following definitions will apply, and where appropriate, terms used in the singular will also include the plural, and vice versa. If any definition set forth below conflicts with any document incorporated herein by reference, the definition set forth below shall prevail.

[0059] As used herein, the words "a" or "an" when used with the term "comprising" in the claims and / or the specification may mean "one", but they also conform to the meaning of "one or more", "at least one" and / or "one or more than one".

[0060] The term "about" or "approximately" means within an acceptable error range for a particular value determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, according to the practice in the art, "about" can mean within three or more standard deviations. Alternatively, "about" can mean a range within up to 20%, preferably up to 10%, more preferably up to 5%, and more preferably up to 1% of a given value. Alternatively, particularly for systems or processes, the term can mean within an order of magnitude, preferably within five times, and more preferably within two times of a value.

[0061] As used herein, the terms "comprise(s)", "include(s)", "having", "has", "can", "contain(s)" and variations thereof are intended to serve as open transitional phrases, terms or words that do not exclude additional actions or structures. The present disclosure also contemplates other embodiments "comprising", "consisting of", and "consisting essentially of" the embodiments or elements described herein, whether or not explicitly stated.

[0062] As used herein, the term "about" or "approximately" means within an acceptable error range for a particular value determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, according to the practice in the art, "about" can mean within three or more standard deviations. Alternatively, "about" can mean a range of up to 20%, preferably up to 10%, more preferably up to 5%, and more preferably up to 1% of a given value.

[0063] As used herein, the term "allergic" refers to an unregulated or unregulated sensitivity of the immune system to normally harmless substances (e.g., substances present in the environment), particularly a hypersensitivity reaction. As previously described herein, allergic inflammatory skin diseases are characterized by the production of erythema, pain, redness, swelling, and small blisters or papules on the skin. Parts of the body commonly affected by atopic dermatitis include the head, pinnae, feet, ventral abdomen, and armpits. Common allergy triggers include, but are not limited to: airborne allergens, such as pollen, animal dander, dust mites, and mold; certain foods, especially peanuts, tree nuts, wheat, soy, fish, shellfish, eggs, and milk; insect stings, such as bee or wasp stings; medications, especially penicillin or penicillin-based antibiotics; latex or other contact substances that can cause skin allergic reactions; allergic inflammatory skin diseases including atopic dermatitis, flea allergy dermatitis, urticaria, insect bite allergy, angioedema, inhalation allergy, inhalation allergic dermatitis, food allergy dermatitis, contact dermatitis, miliary dermatitis, eosinophilic granuloma, head and neck pruritus, and generalized pruritus. Therefore, it should be understood in this article that the term "allergic" can be related to both "auto-antigens" and exogenous antigens.

[0064] As used herein, the term "animal" or "animals" refers to ruminants, poultry, pigs, mammals, horses, mice, rats, rabbits, guinea pigs, hamsters, cows, cats or canines. In a specific embodiment, the term "animal" refers to canines. For example, but not limited to, the animal may be a penguin, a falcon, an agouti, an American kestrel, a snake, a bear, a bald eagle, an ant, an impala, an antelope, an armadillo, an Australian brush turkey, a babirusa, a white-headed eagle, a long-crested starling, a fox, a bat, a sunbird, a bee, a beetle, a panda, a binturong, a bird of paradise, a python, a bonobo, a white-lined wildebeest, a brown bear, a caecilian, a camel, a caracal, a chameleon, a cheetah, a chimpanzee, a chimpanzee, a cichlid, a clouded leopard, a cobra, a cockatoo, a crocodile, a hawk, an Asian jackal, a dolphin, a platypus, an echidna, an elephant, an emu, a flamingo, a Falkland mongoose, a frog, a toad, a toad, Galapagos, gelada, giant anteater, giant panda, Gila monster, giraffe, goat, sheep, frog, gorilla, Gossy sparrow, Guam rail, guanaco, long-tailed monkey, hippopotamus, hornbill, ibis, iguana, jacana, jaguar, heron, kangaroo, wallaby, kingfisher, king snake, drongo, kiwi, mountain antelope, koala, koi, Komodo dragon, ladybug, kookaburra, lemur, leopard, lion, lizard, lynx, macaw, magpie goose, manatee, mandrill, white-browed monkey, marsupial, mongoose, starling, monkey, ocelot, okapi, opossum, gorilla, gemsbok, ostrich, otter, owl, painted dog, parrot, peacock, pelican, polar bear, porcupine, prairie dog, pronghorn antelope, Przewalski's horse, raccoon, shelduck, red panda, reindeer, rhino, ring-tailed panda, rock hyrax, saiga antelope, scorpion, sea lion, clergy bird, serval, siamang, snow leopard, spider, stork, sun bear, Suriname toad, takin, tapir, Tasmanian devil, hedgehog, tiger, toucan, lizard, tortoise, vulture, warthog, barred finch, whale, Cape buffalo, wolf, hairy-nosed wombat, or zebra.

[0065] As used herein, the term "canine" includes animals selected from the group consisting of wolves, coyotes, jackals, dingoes, jackals, foxes, raccoon dogs and dogs, including pet animals. As used herein, "dog" includes wild dogs and domestic dogs. In a specific embodiment, the term "dog" refers to a domestic dog.

[0066] As used herein, the term "drug" refers to any substance or composition that has therapeutic, curative or preventive properties for animal diseases. By extension, pharmaceutical products include any substance or composition that can be used or administered to animals for medical diagnosis or to restore, correct or change their physiological functions by exerting pharmacological, immunological or metabolic effects.

[0067] In the detailed description of the present invention, references to "embodiments", "an embodiment", "one embodiment", "in various embodiments", etc. indicate that the embodiments described may include specific features, structures, or characteristics, but not every embodiment may include the specific features, structures, or characteristics. In addition, such phrases do not necessarily refer to the same embodiment. In addition, when a specific feature, structure, or characteristic is described in conjunction with an embodiment, it is considered that whether or not explicitly described, those skilled in the art are aware of the effects of combining such features, structures, or characteristics with other embodiments. After reading the detailed description, those skilled in the relevant art will be very clear about how to implement the present disclosure in alternative embodiments.

[0068] As used herein, the term "enantiomers" refers to a pair of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture or racemate. Where appropriate, the term is used to refer to a racemic mixture.

[0069] As used herein, the term "enantiomerically pure" refers to a sample that consists of a single enantiomer within the limits of detection.

[0070] As used herein, the term "diastereomer" refers to a stereoisomer having at least two asymmetric atoms but not mirror images of each other. Absolute stereochemistry is specified according to the Cahn-Ingold-Prelog R-S system. When a compound is a pure enantiomer, the stereochemistry at each chiral carbon can be specified with R or S. The unknown absolute configuration of the analyzed compound can be specified as (+) or (-) according to the direction (right-handed or left-handed) in which it rotates plane polarized light at the wavelength of the sodium D line. The compound of the disclosed subject contains one or more asymmetric centers, so enantiomers, diastereomers and other stereoisomeric forms can be produced, which can be defined as (R)- or (S)- according to absolute stereochemistry. The disclosed subject is intended to include all such possible isomers, including racemic mixtures, optically pure forms and intermediate mixtures. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents, or analyzed using conventional techniques. If the compound contains a double bond, the substituent can be an E or Z configuration. If the compound contains a disubstituted cycloalkyl group, the cycloalkyl substituent may have a cis or trans configuration. All tautomeric forms are intended to be included.

[0071] As used herein, the term "isomer" refers to different compounds with the same molecular formula but different atomic arrangements and configurations. In addition, as used herein, the term "stereoisomer" refers to any of the various stereoisomer configurations that can exist for a given compound of the disclosed subject matter, and includes geometric isomers. It is understood that substituents can be attached to the chiral center of a carbon atom. Therefore, the term stereoisomer includes enantiomers, diastereomers, or racemates of a compound. In addition, as used herein, the term "constitutional isomers" refers to different compounds with the same number and type of atoms but different ways of connecting atoms, such as, but not limited to, tautomers.

[0072] As used herein, the term "food composition" or "diet" encompasses all foods, diets, food supplements, or materials that may contain protein, carbohydrates, and / or crude fat. Food may also contain supplementary substances or additives, such as minerals and vitamins (see "Merriam-Webster's Collegiate Dictionary", 10th edition, 1993). Such food compositions may be nutritionally complete or not nutritionally complete. In one embodiment, the animal food composition according to the disclosed subject matter is a nutritionally complete food composition. Illustratively, the food composition described herein may include, but is not limited to, protein, crude fat, ash, crude fiber, starch, calcium, phosphorus, sodium, chloride, potassium, magnesium, iron, water, copper, manganese, zinc, selenium, vitamin A, vitamin D3, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin B7, vitamin B9, choline chloride, arachidonic acid, ω3 fatty acids, or ω6 fatty acids.

[0073] As used herein, "food supplement" refers to concentrated sources of nutrients, substances used for nutritional or physiological purposes, or plants and plant preparations intended to make up for deficiencies in the regular diet of an animal. Food supplements are usually in capsule, lozenge, tablet, pill, powder bag or liquid form (ampoules, vials with droppers).

[0074] As used herein, the term "inflammation" refers to a localized response to cellular injury characterized by capillary dilation, leukocyte infiltration, redness, heat, and pain.

[0075] As used herein, "nutritional comprehensive" means that the composition provides comprehensive and balanced nutritional requirements for animals (and in a specific embodiment, dogs). Therefore, a nutritionally adequate feed is a feed that can be used as the sole ration to feed the animal (e.g., the dog) and can sustain life in the absence of additional food (except water). The food composition may contain a carrier, a diluent, or an excipient. Depending on the intended use, a carrier, a diluent, or an excipient suitable for animal use may be selected, such as a canine, such as a dog. In general, a nutritionally comprehensive composition comprises at least one protein (or polypeptide) source such as a protein extract, at least one vitamin source, at least one mineral source, at least one trace element source, and at least one fat source.

[0076] As used herein, the term "preventing" may also include reducing the likelihood of a given condition occurring or reoccurring in an animal.

[0077] As used herein, the terms "treating" or "treatment" means reversing, alleviating, inhibiting the progression of, or ameliorating the disease or condition to which such term applies, or reversing, alleviating, inhibiting the progression of, or ameliorating one or more symptoms of such disease or condition.

[0078] As used herein, the term "wet food" or "wet food composition" generally refers to a food composition having a moisture content of about 30% by weight or more, generally more than about 40% by weight, relative to the gross weight of the food composition. Preferably, the moisture content of the wet food composition is less than about 90% by weight relative to the gross weight of the food composition. Typically, it is the final product of a process comprising a terminal sterilization step (rather than a drying step). In a specific embodiment, the wet food comprises a chunk form, more particularly a chunk of meat in a gravy form. Preferably, the wet food comprises chunks of meat and gravy, chunks of aspic, bread, meat pie, mousse, minced meat, in a small chunk form. "Chunks and gravy" products include preformed meat particles prepared by making minced meat and passing this minced meat under pressure through an outlet and then cooking. The product (e.g., cooked meat) is cut into chunks and finally mixed with gravy or sauce. The two components are then filled into a container, typically a can or pouch, which is sewn or sealed and sterilized. In contrast to minced meat, meat chunks and gravy compositions are prepared with physically separated, discrete chunks (i.e., minced meat chunks and cereal chunks). These discrete particles are present in a gravy-type liquid in the final container. When fed, meat chunks and gravy products flow out of the can and can be easily mixed with other dry products. Although meat chunks and gravy products can better maintain the integrity of the individual ingredients, the heterogeneous formulations of meat chunks and gravy products are sometimes not favored by consumers. Wet food compositions are usually packaged in canned containers and are considered "wet" in appearance due to the moisture contained therein. Two types of wet compositions are generally known in the art. The first is referred to as "minced meat patties" in the art. Patty products are usually prepared by contacting a mixture of the ingredients under heating to produce a substantially uniform intracellular honeycomb mass or "minced meat patties". The minced meat patty pieces are then loaded into cylindrical containers, such as cans. After packaging, the minced meat patties will take on the shape of the container, so when feeding companion animals, the minced meat patties must be cut. The wet food composition is preferably packaged. In this way, the consumer is able to identify the ingredients in the food from the packaging and confirm that it is suitable for the particular pet in question. The packaging can be metal, plastic, paper or card.

[0079] As used herein, the term "dry food" or "dry food composition" generally refers to a food or composition having a moisture content of less than about 12% by weight relative to the total weight of the food composition, and generally even less than about 7% by weight relative to the total weight of the food composition. In a specific embodiment, the dry food according to the disclosed subject matter has a moisture content of up to about 12% by weight. In some embodiments, the dry food has a moisture content of about 7% by weight or less, such as about 5% by weight. In a specific embodiment, the dry food may have a moisture content of more than about 3% by weight relative to the total weight of the food composition. For example, the examples provided herein illustrate a dry food having a moisture content of about 9.5% by weight relative to the total weight of the food composition. In certain embodiments, the dry food consists of kibble. In a non-limiting example, kibble includes particles; pellets; small pieces of pet food, dehydrated meat, meat analogs, vegetables and combinations thereof; and pet treats, such as jerky or dried vegetables, rawhide and biscuits. The dry food composition can be made by mixing the raw materials together and kneading to make a consistent dough that can be cooked. Typically, it may be the final product of a process comprising an extrusion step and a subsequent drying step.

[0080] The process of making dry food is usually completed by baking and / or extrusion. The dough is usually sent into a machine called an expander and / or extruder, which uses pressurized steam or hot water to cook the raw materials. In the extruder, the dough is under extreme pressure and high temperature. The dough is then pushed through a die (a hole of a specific size and shape) and then cut with a knife. The puffed dough piece is made into a coarse-ground food by passing it through a dryer to reduce the moisture to a specified target and ensure the stability of the food before consumption. The coarse-ground food is then sprayed with fat, oil, minerals, vitamins, natural extract mixtures, and optionally sealed in a package. Preferably, the dry food composition is packaged. In this way, consumers can identify the ingredients in the food from the package and confirm that it is suitable for the specific pet, i.e., dog. The packaging can be metal, plastic, paper or card.

[0081] As used herein, the term "semi-wet food" or "semi-wet food composition" generally refers to a food composition with a moderate moisture content of about 12% by weight to about 30% by weight relative to the gross weight of the food composition. Therefore, such semi-wet food compositions are generally the final product of a process that allows moisture content values ​​between dry food and wet food. In some embodiments, the process may include a step of adding a humectant. In some embodiments, the process includes an extrusion step and a subsequent treatment step with superheated steam (SHS). In some embodiments, the semi-wet food according to the disclosed subject matter contains more than about 12% by weight and up to about 30% by weight of moisture relative to the gross weight of the food composition. Illustratively, the semi-wet food composition has about 11% by weight to about 20% by weight of moisture, and / or a water activity of about 0.64 to about 0.75, preferably both, relative to the gross weight of the food composition.

[0082] As a non-limiting example, semi-moist food can be obtained using a superheated steam (SHS) process, such as the processes or methods described in published patent applications WO2009 / 018990, WO2009 / 018996, WO2010 / 112097, WO2014 / 122072, WO2016 / 071372 and / or WO2016 / 071367, the disclosures of which are incorporated herein by reference in their entirety.

[0083] As disclosed herein, in certain embodiments, when the animal food composition is a semi-moist food, it consists of soft semi-moist kibble.

[0084] As disclosed herein, the "moisture content" of an animal food composition can be determined by the loss on drying method, which comprises the following steps:

[0085] (a) weighing a sample of a food composition to obtain a total weight;

[0086] (b) heating the sample of step a) in an oven (e.g., 135±2° C., 240 minutes) until all the water is discharged, thereby obtaining a dry sample;

[0087] (c) weighing the dried sample; thereby obtaining a dry weight;

[0088] (d) Calculate the difference between the total weight and the dry weight to obtain the moisture content as follows:

[0089] Moisture content = (total weight) - (dry weight)

[0090] As used herein, the term "water activity" refers to the ratio of the vapor pressure of water in a food composition divided by the vapor pressure of water under standard conditions. Water activity can be measured using several methods known to those skilled in the art, such as, but not limited to, resistance electrolytic, capacitance or dew point hygrometers. Most preferably, it refers to the method specified by the international standard ISO 21087 related to the determination of water activity in animal food and animal feed.

[0091] As used herein, "solvent" may refer to acetic acid, n-butanol, isopropanol, n-propanol, ethanol, methanol, formic acid, dimethylformamide, dimethyl sulfoxide, acetonitrile, acetone, dichloromethane, tetrahydrofuran, ethyl acetate, n-hexane, benzene, toluene, ether, chloroform, 1,4-dioxane, water or a combination thereof, preferably water. In a non-limiting embodiment, the solvent is a mixture of about 80% w / w water and about 20% w / w ethanol.

[0092] As used herein, the term "weight percent" or "wt%" or "by weight" is intended to refer to: (i) the percentage of the amount of an ingredient / component in a composition by weight to the total weight of the composition; or (ii) the percentage of the amount of an ingredient / component in a material by weight to the weight of the final material or product. Unless otherwise specified, all weight percentages expressed herein are measured by weight of the total weight of the dry matter of the food composition.

[0093] As used herein, the amount of an ingredient expressed in weight / kcal consists of the weight of the ingredient per unit of metabolizable energy (ME) of the total animal food composition. As used herein, the ME parameter is intended to represent the energy value of a food composition that is directly metabolized after consumption. Within the scope of the disclosed subject matter, ME values ​​can be measured by any suitable method known in the art. Illustratively, feeding trials can be used to measure ME values. In practice, the gross energy (GE) of a food is measured in a laboratory, and the amount of food eaten by the animal is recorded. The feces and urine of the animal are collected, and the respective energies are measured, referred to as fecal energy (FE) and urine energy (UE), respectively. ME is then calculated as follows:

[0094] ME (kcal / kg) = [GE - (FE + UE)] / kg of food consumed.

[0095] Alternatively, the ME value can be measured by a mathematical method, in particular taking into account the percentages of crude fat (CF), crude protein (CP) and NFE (carbohydrates) in the composition. In practice, each percentage is multiplied by its respective Atwater Factors. The resulting sum is then multiplied by 10. This mathematical method can be represented by the following formula:

[0096] ME(kcal / kg)=10x[(3.5xCP)+(8.5xCF)+(3.5xNFE)].

[0097] Metabolizable energy can generally be determined according to standard methods, particularly according to the methods of the United States National Research Council.

[0098] As used herein, the amount of the composition represented by weight / kg food composition (e.g., weight / kg complete food) is composed of the weight of the composition of the food composition (e.g., described complete food) of unit weight (in kilograms). As used herein, "complete food" can refer to a quantitative mixture of all dietary ingredients prepared to meet the energy, protein, fat, vitamin and mineral requirements of an animal. As used herein, the amount of the composition represented by weight / kg body weight (Bwt) / day is the daily amount of the composition of an animal (e.g., dog) of unit body weight (in kilograms). In some embodiments, weight / kg body weight refers to the weight of the composition fed to the animal by per kilogram of animal body weight.

[0099] 6.2. Animal food composition

[0100] In certain embodiments, the animal food composition for preventing and / or treating inflammatory diseases or conditions may include glycyrrhizin, additional ingredients and additives. In a specific embodiment, the additional ingredients may include curcumin, linoleic acid, EPA / DHA, taurine, lutein, vitamin E or a combination thereof. In certain embodiments, the additive may include protein, crude fat, fiber, nitrogen-free extract, carbohydrates, starch and / or a combination thereof.

[0101] In certain embodiments, the subject matter of the present disclosure can be formulated as an animal food composition. In specific embodiments, the animal food composition can be fed to a dog according to feeding guidelines.

[0102] 6.2.1. Glycyrrhizin

[0103] As used herein, the term "glycyrrhizin" refers to a component of Glycyrrhiza glabra root (i.e., licorice or liquorice). Glycyrrhizin is the most important compound in licorice and is a triterpene glycoside. Licorice is a perennial plant that occurs naturally or is cultivated in Europe and Asia. In addition, glycyrrhizin is believed to have a variety of pharmacological effects, such as anti-inflammatory, antiviral, anti-tumor, antioxidant and hepatoprotective effects (Sato et al., 1996; Rahman et al., 2006).

[0104] The structure of glycyrrhizin contains a triterpene portion (glycyrrhetinic acid) and two iduronic acid residues. Other names for glycyrrhizin include glycyrrhizic acid, glycyrrhizic acid, glycyrrhetinic acid glycoside, and (3-β,20-β)-20-carboxy-11-oxo-30-norlan-12-en-3-yl-2-O-β-D-pyranoglucuronyl-α-D-pyranoglucuronide.

[0105] Glycyrrhizin can be extracted from various natural plants by several extraction techniques known to those skilled in the art, such as supercritical CO2 extraction, two-phase aqueous extraction, solvent extraction, third phase extraction, microwave-assisted extraction or ultrasound-assisted extraction.

[0106] The CAS registration number of glycyrrhizin is: 1405-86-3, which is characterized by having the following structure:

[0107]

[0108] According to one embodiment, glycyrrhizin may be in the form of a pharmaceutically acceptable salt and / or one of its racemic, enantiomeric, diastereomeric or tautomeric forms.

[0109] Non-limiting examples of pharmaceutically acceptable salts are salts with acids or bases, including ammonium salts such as monoammonium glycyrrhizinate and alkali metal salts such as disodium glycyrrhizinate, trisodium glycyrrhizinate and dipotassium glycyrrhizinate.

[0110] In one embodiment, glycyrrhizin may be present in some naturally occurring extracts and / or plants, or obtained by chemical methods (Shabkhiz MA, Eikani MH, Bashiri Sadr Z, Golmohammad F. Superheated water extraction of glycyrrhizic acid from licorice root. Food Chem. 2016, 210: 396-401).

[0111] According to one embodiment, glycyrrhizin can be extracted from a glycyrrhizin source (e.g., crude licorice). The glycyrrhizin source can be an extract containing glycyrrhizin obtained from a plant material. Preferably, an extract containing glycyrrhizin can be obtained from a plant material containing glycyrrhizin (e.g., crude licorice) by an extraction method comprising at least the following steps:

[0112] (a) providing plant materials containing glycyrrhizin;

[0113] (b) grinding the plant material of step a), preferably in a solvent, thereby obtaining a ground mixture;

[0114] (c) extracting glycyrrhizin from the ground mixture to obtain a glycyrrhizin-containing extract;

[0115] (d) optionally, filtering the glycyrrhizin extract to obtain a filtered glycyrrhizin extract;

[0116] (e) optionally, concentrating the filtered glycyrrhizin extract;

[0117] (f) optionally, spray drying the filtered glycyrrhizin extract to obtain a powder; and

[0118] (g) Optionally, the powder is sieved.

[0119] As used herein, "plant material containing glycyrrhizin" refers to a glycyrrhizin source, preferably a root of Glycyrrhiza glabra, most preferably a glycyrrhizin-containing licorice extract or a glycyrrhizin-containing crude licorice.

[0120] According to some embodiments, the term "plants" or "plant" includes glycyrrhiza. In a specific example, the licorice is selected from the group consisting of: glycyrrhiza acanthocarpa, glycyrrhiza aspera, glycyrrhiza astragalina, glycyrrhiza bucharica, glycyrrhiza echinate, glycyrrhiza eglandulosa, glycyrrhiza eurycarpa, glycyrrhiza foetida, glycyrrhiza foetidissima, glycyrrhiza frearitis, glycyrrhiza glabra, glycyrrhiza gontscharovii, glycyrrhiza iconica, glycyrrhiza inflata, glycyrrhiza truncatum ... korshinskyi, North American liquorice (Glycyrrhiza lepidota), spiny liquorice (Glycyrrhiza pallidiflora), round liquorice (Glycyrrhiza squamulose), three-leaf liquorice (Glycyrrhiza triphylla), Ural liquorice (Glycyrrhiza uralensis) and Yunnan liquorice (Glycyrrhiza yunnanensis).

[0121] The term "licorice" or "liquorice" includes crude licorice, licorice root and licorice root. In a non-limiting embodiment, the glycyrrhizin source consists of licorice root extract (LRE).

[0122] The amount of glycyrrhizin in a given botanical source, extract, or food composition may be expressed as weight per total weight of dry matter of the given botanical source, extract, or composition.

[0123] Relative to the gross weight of liquorice dry matter, liquorice can contain about 1 wt % to about 30 wt %, about 1 wt % to about 25 wt %, about 5 wt % to about 20 wt %, about 6 wt % to about 20 wt %, or about 6 wt % to about 12 wt % glycyrrhizin. As used herein, about 6 wt % to about 12 wt % glycyrrhizin includes about 6.0 wt %, about 6.5 wt %, about 7.0 wt %, about 7.5 wt %, about 8.0 wt %, about 8.5 wt %, about 9.0 wt %, about 9.5 wt %, about 10.0 wt %, about 10.5 wt %, about 11.0 wt %, about 11.5 wt %, about 12.0 wt % glycyrrhizin based on the gross weight of liquorice root dry matter.

[0124] Licorice can be obtained from commercial sources, such as Licorice Root PE 12% Glycyrrhizin Preparation provided by Naturex (Product No.; ED161596).

[0125] In a non-limiting embodiment, the glycyrrhizin source comprises licorice or an extract thereof containing glycyrrhizin. Any other glycyrrhizin source known to those skilled in the art may also be used, particularly any other glycyrrhizin source other than licorice. According to some embodiments, the glycyrrhizin source may be pure glycyrrhizin. In a non-limiting embodiment, the glycyrrhizin source comprises a licorice root extract containing 12% glycyrrhizin prepared using a mixture of 80% water and 20% ethanol.

[0126] In certain embodiments, the presently disclosed subject matter is directed to an animal food composition for use in a method of preventing and / or treating an inflammatory disease or disorder, an allergic inflammatory skin disease, wherein the animal food composition is formulated to provide the animal with a daily amount of at least about 0.02 mg / kg body weight of glycyrrhizin.

[0127] In certain embodiments, the animal food composition is formulated to provide the animal with a daily amount of about 0.02 mg / kg to about 2 mg / kg, about 0.03 mg / kg to about 2 mg / kg, about 0.05 mg / kg to about 1 mg / kg, about 0.1 mg / kg to about 0.8 mg / kg, about 0.2 mg / kg to about 0.6 mg / kg, about 0.02 mg / kg to about 1 mg / kg, or about 1 mg / kg to about 2 mg / kg of body weight of glycyrrhizin.

[0128] As used herein, a daily amount of glycyrrhizin of about 0.02 mg / kg to about 2 mg / kg body weight may include 0.02 mg / kg, about 0.03 mg / kg, about 0.04 mg / kg, about 0.05 mg / kg, about 0.06 mg / kg, about 0.07 mg / kg, about 0.08 mg / kg, about 0.09 mg / kg, about 0.1 mg / kg, about 0.2 mg / kg, about 0.3 mg / kg, about 0.4 mg / kg. / kg, about 0.5mg / kg, about 0.6mg / kg, about 0.7mg / kg, about 0.8mg / kg, about 0.9mg / kg, about 1mg / kg, about 1.1mg / kg, about 1.2mg / kg, about 1.3mg / kg, about 1.4mg / kg, about 1.5mg / kg, about 1.6mg / kg, about 1.7mg / kg, about 1.8mg / kg, about 1.9mg / kg and about 2mg / kg body weight.

[0129] In another embodiment, the animal food composition is formulated to provide a daily amount of about 0.03 mg / kg to about 2 mg / kg, about 0.05 mg / kg to about 1 mg / kg, about 0.1 mg / kg to about 0.8 mg / kg, or about 0.2 mg / kg to about 0.6 mg / kg body weight of glycyrrhizin to the animal. In a specific embodiment, the animal food composition is formulated to provide a daily amount of about 0.2 mg / kg body weight, about 0.4 mg / kg body weight, or about 0.6 mg / kg body weight of glycyrrhizin.

[0130] In certain embodiments, an animal food composition containing a source of glycyrrhizin can be used as a medicament, wherein the animal food composition is formulated to provide a daily amount of at least about 0.02 mg / kg body weight of glycyrrhizin to an animal. In certain embodiments, the medicament provides a daily amount of about 0.02 mg / kg to about 2 mg / kg, about 0.02 mg / kg to about 1 mg / kg, or about 1 mg / kg to about 2 mg / kg body weight of glycyrrhizin to an animal.

[0131] In certain embodiments, the animal food composition comprises a glycyrrhizin source comprising a glycyrrhizin source comprising at least about 5 mg / kg of glycyrrhizin based on the gross weight of the animal food composition dry matter. In certain embodiments, the amount of glycyrrhizin is about 5 mg / kg to about 100 mg / kg based on the gross weight of the animal food composition dry matter. In a specific embodiment, the amount of glycyrrhizin is about 5 mg / kg to about 50 mg / kg, about 5 mg / kg to about 40 mg / kg, about 10 mg / kg to about 75 mg / kg, about 15 mg / kg to about 50 mg / kg, about 20 mg / kg to about 45 mg / kg, or about 50 mg / kg to about 100 mg / kg based on the gross weight of the animal food composition dry matter.

[0132] In certain embodiments, the amount of glycyrrhizin is at least about 5 mg / kg, based on the total weight of the dry matter of the animal food composition. As used herein, at least about 5 mg / kg can include at least about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, about 10 mg / kg, about 11 mg / kg, about 12 mg / kg, about 13 mg / kg, about 14 mg / kg, about 15 mg / kg, about 16 mg / kg, about 17 mg / kg, about 18 mg / kg, about 19 mg / kg, about 20 mg / kg, about 21 mg / kg, about 22 mg / kg, about 23 mg / kg, about 24 mg / kg, about 25 mg / kg, about 26 mg / kg, about 27 mg / kg, about 28 mg / kg, about 29 mg / kg, about 30 mg / kg, about 31 mg / kg, about 32 mg / kg, about 33 mg / kg, about 34 mg / kg, about 35 mg / kg, about 36 mg / kg, about 37 mg / kg, about 38 mg / kg, about 39 mg / kg, about 40 mg / kg, about 41 mg / kg, about 42 mg / kg, about 43 mg / kg, about 44 mg / kg, about 45 mg / kg, about 46 mg / kg, about 47 mg / kg, about 48 mg / kg, about 49 mg / kg, about 50 mg / kg, about 51 mg / kg, about 52 mg / kg, about 53 mg / kg, about 54 mg / kg, about 55 mg / kg, about 56 mg / kg, about 57 mg / kg, about 58 mg / kg, about 59 mg / kg, about 60 mg / kg, about 61 mg / kg, about / kg, about 22mg / kg, about 23mg / kg, about 24mg / kg, about 25mg / kg, about 26mg / kg, about 27mg / kg, about 28mg / kg, about 29mg / kg, about 30mg / kg, about 31mg / kg, about 32mg / kg, about 33mg / kg, about 34mg / kg, about 35mg / kg, about 36mg / kg, about 37mg / kg, about 38mg / kg, about 39mg / kg or about 40mg / kg.

[0133] In certain embodiments, the amount of glycyrrhizin is less than about 100 mg / kg, based on the total weight of the dry matter of the animal food composition. As used herein, less than about 100 mg / kg can include less than about 99 mg / kg, about 98 mg / kg, about 97 mg / kg, about 96 mg / kg, about 95 mg / kg, about 94 mg / kg, about 93 mg / kg, about 92 mg / kg, about 91 mg / kg, about 90 mg / kg, about 89 mg / kg, about 88 mg / kg, about 87 mg / kg, about 86 mg / kg, about 85 mg / kg, about 84 mg / kg, about 83 mg / kg, about 82 mg / kg, about 81 mg / kg, about 80 mg / kg, about 79 mg / kg, about 78 mg / kg, about 77 mg / kg g, about 76 mg / kg, about 75 mg / kg, about 74 mg / kg, about 73 mg / kg, about 72 mg / kg, about 71 mg / kg, about 70 mg / kg, about 69 mg / kg, about 68 mg / kg, about 67 mg / kg, about 66 mg / kg, about 65 mg / kg, about 64 mg / kg, about 63 mg / kg, about 62 mg / kg, about 61 mg / kg, about 60 mg / kg, about 59 mg / kg, about 58 mg / kg, about 57 mg / kg, about 56 mg / kg, about 55 mg / kg, about 54 mg / kg, about 53 mg / kg, about 52 mg / kg, about 51 mg / kg or about 50 mg / kg.

[0134] 6.2.2. Other ingredients

[0135] In certain embodiments, the animal food composition for preventing and / or treating an inflammatory disease or disorder, an allergic inflammatory skin disease further comprises linoleic acid.

[0136] In certain embodiments, the animal food composition disclosed herein for preventing and / or treating inflammatory diseases or disorders, allergic inflammatory skin diseases further comprises one or more Curcuminoids.

[0137] In certain embodiments, the animal food composition further comprises EPA / DHA, taurine, lutein, vitamin E and / or a combination thereof. In some embodiments, the animal food composition may also additionally comprise one or more vitamins A, vitamin B3, vitamin C, zinc, vitamin D, one or more fatty acids and / or a combination thereof.

[0138] 6.2.2.1. Curcuminoids

[0139] As used herein, the term "curcuminoid" or "curcuminoids" refers to phenolic compounds present in the Indian spice turmeric root powder. Turmeric root powder is generally derived from the root of the plant Curcuma longa. Curcuminoids are also found in the roots of other species of plants in the genus Curcuma, Zingiberaceae. In particular, turmeric root powder can contain about 60% to about 80% by weight of curcumin relative to the total weight of turmeric root powder dry matter, about 15% to about 30% by weight of demethoxycurcumin relative to the total weight of turmeric root powder dry matter, and about 2% to about 6% by weight of bisdemethoxycurcumin relative to the total weight of turmeric root powder dry matter. The curcuminoids in the food composition of the present disclosure subject can be in any form, including powder or lipid extract. In a non-limiting embodiment, the curcuminoids can be found in some naturally occurring extracts and / or plants, and can also be obtained or synthesized by chemical means.

[0140] In a non-limiting embodiment, the source of curcuminoids includes turmeric root powder extract, i.e., Curcuma longa. In certain embodiments, the turmeric root powder extract may be from Arjuna Or turmeric root powder extract from Naturex. Any other source of curcuminoids known to those skilled in the art may also be used.

[0141] Other available sources of curcuminoids can also be selected from liposomal curcumin, curcumin nanoparticles, curcumin phospholipid complexes (e.g., MERIVA source, accounting for about 20% of the total curcuminoids, Arjuna accounts for about 90% by weight of total curcuminoids), structural analogs of curcumin (e.g., EF-24), demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin, and commercial / DM, any formulation designed to increase the bioavailability of curcumin.

[0142] Generally, curcuminoids can be found in other plant materials besides turmeric, such as Javanese turmeric (Curcuma xanthorrhiza) and Curcuma zedoania. Pure curcuminoids have low solubility in water. Curcuminoids can be extracted from plants containing curcuminoids (i.e., turmeric root) using organic solvents (e.g., ethanol or acetone).

[0143] In certain embodiments, the curcuminoids according to the presently disclosed subject matter may include compounds of formula (I):

[0144]

[0145] Where R 1 and R 2 Independently selected from a hydrogen atom, a methoxy group, a methyl group, a hydroxyl group and an ethoxy group, or one of its pharmaceutically acceptable salts and / or racemic, enantiomeric, diastereomeric or tautomeric forms.

[0146] In a non-limiting embodiment, R 1 and R 2 Can be the same or different.

[0147] In a non-limiting embodiment, the curcuminoid compound is selected from the group consisting of curcumin, demethoxycurcumin, bismethoxycurcumin, tetrahydrocurcumin or a combination thereof.

[0148] For reference, the chemical structures of curcumin (I), demethoxycurcumin (II), bismethoxycurcumin (III), and tetrahydrocurcumin (IV) are as follows:

[0149]

[0150] In certain embodiments, the curcuminoid is curcumin. In a particular embodiment, the source of curcuminoids (i.e., curcumin) may be turmeric root powder.

[0151] In certain embodiments, the animal food composition comprises a source of Curcuminoids in an amount ranging from about 0.01 g / Mcal to about 0.1 g / Mcal, about 0.01 g / Mcal to about 2 g / Mcal, about 0.01 g / Mcal to about 5 g / Mcal, about 5 g / Mcal to about 10 g / Mcal, or about 0.01 g / Mcal to about 10 g / Mcal. In certain embodiments, the animal food composition comprises a source of Curcuminoids in an amount less than about 5 g / Mcal, less than about 2 g / Mcal, or less than about 0.5 g / Mcal.

[0152] In particular embodiments, the animal food composition comprises a source of Curcuminoids in an amount ranging from about 0.01 wt % to about 0.1 wt %, about 0.01 wt % to about 5 wt %, about 5 wt % to about 10 wt %, about 0.1 wt % to about 10 wt %, or about 0.01 wt % to about 10 wt %, based on the total weight of the dry matter of the food composition.

[0153] As used herein, about 0.01 wt % to about 10 wt % of a source of Curcuminoids may include about 0.01 wt %, about 0.1 wt %, about 1 wt %, about 2 wt %, about 3 wt %, about 4 wt %, about 5 wt %, about 6 wt %, about 7 wt %, about 8 wt %, about 9 wt % or about 10 wt % of a source of Curcuminoids based on the total weight of the dry matter of the food composition.

[0154] As used herein, about 0.01% to about 0.1% by weight of a source of Curcuminoids may include about 0.01%, about 0.011%, about 0.012%, about 0.013%, about 0.014%, about 0.015%, about 0.016%, about 0.017%, about 0.018%, about 0.019%, about 0.02%, about 0.021%, about 0.022%, about 0.023%, about 0.024%, about 0.025%, about 0.026%, about 0.027%, about 0.028%, about 0.029%, about 0.030%, about 0.031%, about 0.032%, about 0.033%, about 0.034%, about 0.035%, about 0.036%, about 0.037%, about 0.038%, about 0.039%, about 0.040%, about 0.041%, about 0.042%, about 0.043%, about 0.044%, about 0.045%, about 0.046%, about 0.047%, about 0.048%, about 0.049%, about 0.050%, about 0.051%, about 0.052%, about 0.053%, about 0.054%, about 0.055%, about 0.056%, about 0.057%, about 0.058%, about 0.059%, about 0.060%, about 0.061%, about 0.062%, about 0.063%, about 0.064%, about 0.065%, about 0.066%, about 0.067%, about 0.068%, about 0.069%, About 0.029 wt%, about 0.03 wt%, about 0.031 wt%, about 0.032 wt%, about 0.033 wt%, about 0.034 wt%, about 0.035 wt%, about 0.036 wt%, about 0.037 wt%, about 0.038 wt%, about 0.039 wt%, about 0.04 wt%, about 0.041 wt%, about 0.042 wt%, about 0.043 wt%, about 0.044 wt%, about 0.045 wt%, about 0.046 wt%, about 0.047 wt%, about 0.048 wt%, about 0.049 wt%, about 0.05 wt%, about 0.051 wt%, about 0.052 wt%, about 0.053 wt%, about 0.054 wt%, about 0.055 wt%, about 0.056 wt%, about 0.057 wt%, about 0.058 wt%, about 0.059 wt%, about 0.060 wt%, about 0.061 wt%, about 0.062 wt%, about 0.063 wt%, about 0.064 wt%, about 0.065 wt%, about 0.066 wt%, about 0.067 wt%, about 0.068 wt%, about 0.069 wt%, about 0.070 wt%, about 0.071 wt%, about 0.072 wt%, about 0.073 wt%, about 0.074 wt%, about 0.075 0.053 wt%, about 0.054 wt%, about 0.055 wt%, about 0.056 wt%, about 0.057 wt%, about 0.058 wt%, about 0.059 wt%, about 0.06 wt%, about 0.061 wt%, about 0.062 wt%, about 0.063 wt%, about 0.064 wt%, about 0.065 wt%, about 0.066 wt%, about 0.067 wt%, about 0.068 wt%, about 0.069 wt%, about 0.07 wt%, about 0.071 wt%, about 0.072 wt%, about 0.073 wt%, about 0.074 wt%, about 0.075 wt%, about 0.076 wt%, about 0.0 77 wt%, about 0.078 wt%, about 0.079 wt%, about 0.08 wt%, about 0.081 wt%, about 0.082 wt%, about 0.083 wt%, about 0.084 wt%, about 0.085 wt%, about 0.086 wt%, about 0.087 wt%, about 0.088 wt%, about 0.089 wt%, about 0.09 wt%, about 0.091 wt%, about 0.092 wt%, about 0.093 wt%, about 0.094 wt%, about 0.095 wt%, about 0.096 wt%, about 0.097 wt%, about 0.098 wt%, about 0.099 wt%, and about 0.1 wt% of a source of Curcumin compounds.

[0155] In certain embodiments, the source of Curcuminoids may consist of pure Curcuminoids.

[0156] In a non-limiting example, an animal food composition (particularly in the form of dry food) suitable for small dogs (see the classification provided in the specification) may include about 0.002% by weight of glycyrrhizin and about 0.0275wt% of Curcuminoids, relative to the total weight of the composition. According to another example, an animal food composition (particularly in the form of dry food) suitable for medium-sized dogs or large dogs (see the classification provided in the specification) may include about 0.003wt% of glycyrrhizin and about 0.0275wt% of Curcuminoids, relative to the total weight of the composition. The animal food composition described herein may be formulated to provide a daily amount of about 77mg / kg of Curcuminoids to an animal, particularly in the form of wet food.

[0157] 6.2.2.2. Linoleic acid

[0158] As used herein, the term "linoleic acid" refers to a polyunsaturated omega-6 fatty acid that is one of the two essential fatty acids for animals.

[0159] To measure the content of linoleic acid in a food composition, one skilled in the art may refer to any well-known technique. For example, a method based on standard NF EN ISO 5508 / 5509 by gas chromatography may be used. Therefore, in some embodiments, the animal food composition described herein comprises one or more substances that are a source of linoleic acid.

[0160] The linoleic acid source, i.e., the material containing linoleic acid, can include vegetable oils, but animal oils or crude fats can also be used. The linoleic acid source can include safflower oil, sunflower oil, soybean oil, sesame oil, rapeseed oil, other vegetable oils or animal oils / crude fats, meat, or a combination of two or more thereof. In certain embodiments, the linoleic acid source is selected from the group consisting of safflower oil, sunflower oil, soybean oil, sesame oil, rapeseed oil, meat, and a combination thereof.

[0161] In certain embodiments, the animal food composition comprises linoleic acid in an amount ranging from about 1 g / Mcal to about 20 g / Mcal, about 1 g / Mcal to about 10 g / Mcal, about 8 g / Mcal to about 12 g / Mcal, about 10 g / Mcal to about 12 g / Mcal, or about 10 g / Mcal to about 20 g / Mcal.

[0162] In certain embodiments, the animal food composition comprises linoleic acid in an amount ranging from about 2 wt % to about 10 wt %, about 2 wt % to about 5.5 wt %, or about 5.5 wt % to about 10 wt %, relative to the total weight of dry matter of the animal food composition.

[0163] 6.2.2.3.EPA / DHA

[0164] As used herein, the term "EPA / DHA" refers to a fatty acid or fatty acid mixture consisting of: (i) eicosapentaenoic acid (EPA) alone, (ii) docosahexaenoic acid (DHA) alone, or (iii) a combination of eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA). Therefore, as used herein, the amount of "EPA / DHA" refers to (i) the amount of EPA in the absence of DHA, (ii) the amount of DHA in the absence of EPA, or (iii) the amount of EPA and DHA combined.

[0165] In certain embodiments, the animal food composition comprises a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in a weight ratio of EPA:DHA of about 0.0001:1000 to about 1000:0.0001. In certain embodiments, the weight ratio of EPA:DHA is about 0.0001:100, about 1:1, or about 0.1:0.0001, relative to the total weight of the dry matter of the animal food composition. In specific embodiments, the weight ratio of EPA:DHA can be about 0.1:100, about 100:0.1, or 0.1 to 100. In specific embodiments, the weight or energy ratio of EPA to DHA can be 0.0001 to 1000, relative to the total weight of the dry matter of the animal food composition.

[0166] According to some embodiments, the animal food composition comprises EPA / DHA in an amount of about 0.1 g / Mcal to about 7 g / Mcal, about 0.1 g / Mcal to about 3 g / Mcal, about 1 g / Mcal to about 2 g / Mcal, about 1.25 g / Mcal to about 1.75 g / Mcal, or about 3 g / Mcal to about 7 g / Mcal. In certain embodiments, the animal food composition comprises EPA / DHA in an amount of about 0.1 wt % to about 5 wt %, about 0.1 wt % to about 2.5 wt %, or about 2.5 wt % to about 5 wt %, relative to the total weight of the dry matter of the animal food composition.

[0167] 6.2.2.4. Taurine

[0168] Taurine is a non-essential amino acid obtained from meat and fish. It acts as a precursor molecule to stimulate the production of glycosphingolipids in the skin. Glycosphingolipids have antimicrobial properties.

[0169] Taurine according to the presently disclosed subject matter can have the following structure:

[0170]

[0171] or a pharmaceutically acceptable salt and / or one of its racemic, enantiomeric, diastereomeric or tautomeric forms.

[0172] In certain embodiments, the animal food composition comprises taurine in an amount of about 1 g / Mcal to about 2 g / Mcal, about 1 g / Mcal to about 1.5 g / Mcal, or about 1.5 g / Mcal to about 2 g / Mcal.

[0173] 6.2.2.5. Lutein

[0174] As used herein, "lutein" refers to xanthophyll and is one of the known naturally occurring carotenoids. Lutein is a lipophilic molecule that is generally insoluble in water.

[0175] Lutein is synthesized only by plants and, like other xanthophylls, is found in high concentrations in green leafy vegetables such as spinach, kale, and yellow carrots. Lutein and zeaxanthin are isomers that differ only in the position of one double bond. The major natural stereoisomer of lutein is (3R,3'R,6'R)-β,ε-carotene-3,3'-diol. Lutein is present in plants as fatty acid esters, in which one or two fatty acids are bound to two hydroxyl groups.

[0176] Lutein according to the presently disclosed subject matter may have the following structure:

[0177]

[0178] or a pharmaceutically acceptable salt and / or one of its racemic, enantiomeric, diastereomeric or tautomeric forms.

[0179] In certain embodiments, the animal food composition comprises lutein in an amount of about 0.001 g / Mcal to about 0.002 g / Mcal, about 0.001 g / Mcal to about 0.0015 g / Mcal, or about 0.0015 g / Mcal to about 0.002 g / Mcal.

[0180] 6.2.2.6 Vitamin E

[0181] Vitamin E is a general term for several biologically similar compounds, including tocopherols and tocotrienols with the same biological activity. The biological form of the most biologically active vitamin E (also the most active antioxidant) in animal tissues is alpha-tocopherol. Vitamin E cannot be synthesized in vivo. Vitamin E can prevent the loss of cell membrane integrity, which can have an adverse effect on cell and organelle function. Vitamin E according to one aspect of the disclosed subject matter can be in any form. It can be a liquid, a semisolid or a solid. It can be a tocopherol or a tocotrienol. It can be alpha-tocopherol, (dx or dl-oc) beta-tocopherol (d-, B or dl-), gamma-tocopherol (dot or dim), delta-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol or delta-tocotrienol. In a specific embodiment, it is alpha-tocopherol.

[0182] In certain embodiments, the source of vitamin E is not limiting. The source of vitamin E may include vitamin E acetate (e.g., tocopheryl acetate), vitamin E acetate adsorbate, or spray-dried vitamin E acetate. In certain embodiments, the source of vitamin E is synthetic, but natural sources may also be used.

[0183] For reference, vitamin E according to the presently disclosed subject matter can have the following structure:

[0184]

[0185] or a pharmaceutically acceptable salt and / or one of its racemic, enantiomeric, diastereomeric or tautomeric forms.

[0186] In certain embodiments, the animal food composition comprises vitamin E in an amount from about 0.2 g / Mcal to about 0.3 g / Mcal, from about 0.2 g / Mcal to about 0.25 g / Mcal, or from about 0.25 g / Mcal to about 0.3 g / Mcal.

[0187] 6.2.3. Additives

[0188] In some embodiments, the animal food compositions described herein are nutritionally complete and may also contain additives, such as protein, crude fat, crude fiber, nitrogen-free extract, ash, minerals, vitamins, or seasonings.

[0189] It should be readily understood that each embodiment of the animal food composition encompassed by the presently disclosed subject matter includes a plurality of ingredients, each ingredient being included in the composition at a given weight percentage compared to the total weight of dry matter of the animal food composition.

[0190] The animal food composition disclosed herein comprises protein, crude fat, ash, fiber, NFE and optionally one or more other additives, such as vitamins, minerals, etc., based on the total weight of the dry matter of the animal food composition, wherein the sum of the weight of each ingredient contained is 100 weight %.

[0191] Protein

[0192] In certain embodiments, an animal food composition according to the disclosed subject matter may also contain a protein source. Thus, the protein level should be high enough to ensure maintenance of lean body mass. An animal food composition may contain one or more different protein sources.

[0193] In certain embodiments, the animal food compositions described herein may include a plurality of proteins contained in a protein source used in the manufacturing process. In certain embodiments, the animal food compositions described herein may include a plurality of proteins from a plurality of protein sources.

[0194] In some embodiments, the protein is not hydrolyzed. In some other embodiments, the protein may be present in the form of at least partial hydrolysis or even complete hydrolysis. According to the animal food composition of the present disclosure, protein in the form of meat or animal-derived material (e.g., beef, chicken, turkey, mutton, fish, blood plasma, bone marrow, or a combination thereof) may be incorporated. In some embodiments, the animal food composition described herein may not contain meat. In non-limiting embodiments, the animal food composition not containing meat includes a meat alternative protein source, such as soybeans, corn gluten, or any other protein-containing soy product, to provide a protein source. The animal food composition disclosed herein may include additional protein sources, such as soy protein concentrate, milk protein, gluten, etc.

[0195] 6.2.3.2. Crude fat

[0196] Animal food compositions according to the present disclosure can also contain nutritionally appropriate amounts of crude fat. The expression "crude fat" used in this specification includes crude fat and / or oil acceptable to any food, regardless of their consistency at room temperature, that is, regardless of whether the "crude fat" exists in a substantially fluid form or in a substantially solid form. Animal food compositions according to the present disclosure theme can include crude fat from animal sources and / or plant sources. Crude fat can be provided by any of the various sources known to those skilled in the art. Plant crude fat sources include, but are not limited to, wheat, sunflower, safflower, rapeseed, olive, borage, linseed, peanut, blackcurrant seed, cottonseed, wheat germ, corn germ, and oil and other plant crude fat sources derived from these. Animal sources can include, for example, but not limited to, chicken crude fat, turkey crude fat, beef crude fat, duck crude fat, pork crude fat, mutton crude fat, fish oil or any meat, meat by-products, seafood, dairy products, eggs, etc. The crude fat content of food can be measured by any number of methods known to those skilled in the art.

[0197] 6.2.3.3. Fiber

[0198] Fiber is optionally included in the animal food composition disclosed herein. The expression "fiber" is similar to "dietary fiber", and should be interpreted as total fiber for the purpose of the present disclosure, indicating that it includes soluble fiber and insoluble fiber. Soluble fiber can be defined as resisting digestion and absorption in the small intestine and undergoing complete or partial fermentation in the large intestine, in contrast to insoluble fiber, which can be defined as non-starch polysaccharides that resist digestion and absorption in the small intestine and resist fermentation in the large intestine. Soluble fiber is considered to have a prebiotic effect by providing short-chain fatty acids as an energy source to colon cells. Insoluble fiber is considered to be useful for transport and ballast. Non-limiting examples of fiber include beet pulp, guar gum, chicory root, psyllium, pectin, blueberry, cranberry, pumpkin, apple, oat, beans, citrus, barley or peas, and a second group including cellulose, whole wheat products, wheat oats, corn bran, linseed, grapes, celery, green beans, cauliflower, potato peels, fruit peels, vegetable peels, peanut shells and soy fiber.

[0199] 6.2.3.4. Nitrogen-free extract (NFE)

[0200] As used herein, and as commonly understood in the art, nitrogen-free extract (NFE) consists of a soluble carbohydrate portion that may be optionally included in the food composition disclosed herein. NFE may include a variety of soluble polysaccharides, starches, gums, mucilages, and pectins (if present in the food composition). Therefore, as commonly known in the art, NFE does not include the insoluble carbohydrate portion of crude fiber materials, which in certain embodiments may be present in the food composition. Typically, the content of nitrogen-free extract in a food composition is determined by subtracting the content of each other component (protein, crude fat, crude fiber, ash) from the total dry matter of the food composition. In embodiments where the qualitative and quantitative characteristics of the food composition are expressed as energy density (e.g., metabolic energy density in g / Mcal), the NFE content is determined by subtracting the energy value of each other component (protein, crude fat, crude fiber, ash) from the energy value of the entire food composition. In embodiments where the qualitative and quantitative characteristics of a food composition are expressed as weight percentages (e.g., weight percentages based on the total weight of dry matter of the composition), the NFE content is determined by subtracting the weight percentages of the other components (protein, crude fat, crude fiber, ash) from the total weight of the food composition.

[0201] 6.2.3.5. Carbohydrates

[0202] As used herein, the term "carbohydrate" refers to a mixture of polysaccharides and sugars that are metabolized to produce energy when hydrolyzed in vivo. The carbohydrate content of a food can be determined by any number of methods known to those skilled in the art. Carbohydrates can be provided as various carbohydrate sources known to those skilled in the art, including starch (e.g., any variety, corn, wheat, barley), beet pulp (which contains small amounts of sugar), and psyllium.

[0203] 6.2.3.6. Starch

[0204] Important sources of nitrogen-free extracts that may be optionally included in the animal food compositions disclosed herein include starch. As used herein, the term "starch" refers to a polysaccharide composed of straight-chain starch and amylopectin. Starch is present in many plant tissues in the form of microparticles, typically between 1 μm and 100 μm in diameter, depending on the plant source. Chemically, starch is a polysaccharide composed of α-D-pyranose glucopyranosyl units linked together with α-D (1-4) and / or α-D (1-6) bonds, and consists of two types of molecules: straight-chain starch, a linear polyglucan composed of approximately 1000 α-D (1-4) linked glucoses; and amylopectin, a branched glucan, composed of approximately 4000 glucoses, with branches appearing in the form of α-D (1-6) bonds. As used herein, starch includes various crystal structures of type A, type B, and type C starch, which contain different proportions of amylopectin. Type A starch is mainly found in cereals, while type B starch is mainly found in tubers and starches rich in straight-chain starch. C-type starch is composed of a mixture of A-type and B-type starch, and is mainly found in beans. Typically, digestible starch is broken down (hydrolyzed) by alpha-amylase, glucoamylase and sucrase-isomaltase in the small intestine to produce free glucose, which is then absorbed. The starch contained in the food composition of the present disclosure can be any starch suitable for dietary purposes. In fact, the natural starch contained in the raw materials for preparing the animal food composition described herein is prone to change during the manufacturing process. The amount of starch in the animal food composition includes the amount of starch contained in the total amount of the raw materials of the animal food composition. However, the amount of starch contained in the animal food composition disclosed herein is equal to the total amount of starch contained in the raw materials for preparing the animal food composition. If not yet known, the starch content of the raw materials for preparing the animal food composition described herein can be determined according to conventional techniques known in the art, and in particular according to known polarimetry, for example, according to NF EN ISO 10520. In some embodiments, the raw material may contain modified starch or pregelatinized starch. The starch content can be determined according to NF EN ISO 15914.

[0205] 6.2.3.6. Ash content

[0206] Ash content, if specified as an analytical measurement of a food composition described herein, is a measure of the total amount of minerals contained therein. Mineral content is a measure of the amount of specific inorganic components contained therein, including calcium (Ca), sodium (Na), potassium (K), and chloride (Cl).

[0207] 6.2.4. Animal food composition formulation

[0208] The presently disclosed subject matter also relates to an animal food composition comprising a source of glycyrrhizin, wherein the amount of glycyrrhizin is greater than 5 mg / kg based on the total weight of dry matter of the animal food composition.The animal food composition described herein may be as described above.

[0209] According to one embodiment, the amount of glycyrrhizin is from about 5 mg / kg to about 100 mg / kg based on the total weight of dry matter of the animal food composition.

[0210] In certain embodiments, the amount of glycyrrhizin can be about 5 mg / kg to about 100 mg / kg, about 10 mg / kg to about 75 mg / kg, about 15 mg / kg to about 50 mg / kg, or about 20 mg / kg to about 45 mg / kg, based on the total weight of the dry matter of the animal food composition.

[0211] In certain embodiments, the glycyrrhizin source may include at least one of the plants of the genus Glycyrrhiza, preferably the root of Glycyrrhiza glabra, i.e., Glycyrrhiza glabra. In certain embodiments, the glycyrrhizin source is Glycyrrhiza glabra. In a specific embodiment, the glycyrrhizin source in the animal food composition includes a licorice root extract.

[0212] In a specific embodiment, the glycyrrhizin source is present in an amount of about 0.01 g / Mcal to about 0.1 g / Mcal, based on the total weight of the animal food composition dry matter. In a specific embodiment, the glycyrrhizin source is present in an amount of about 0.01 wt % to about 10 wt %, based on the total weight of the animal food composition dry matter.

[0213] In certain embodiments, the animal food composition is a nutritionally complete animal food composition, a food supplement, or a covering composition. In some embodiments, the animal food composition consists of kibble. In a specific embodiment, the animal food composition comprises a nutritionally complete animal food composition. In a specific embodiment, the animal food composition is formulated for oral administration. In certain embodiments, the animal food composition comprises a food supplement and / or a medicament.

[0214] In specific embodiments, the animal food composition as described herein further comprises linoleic acid. In certain embodiments, the linoleic acid source is selected from the group consisting of safflower oil, sunflower oil, soybean oil, sesame oil, rapeseed oil, meat, and combinations thereof.

[0215] In certain embodiments, the animal food composition further comprises curcuminoids, linoleic acid, EPA / DHA, taurine, lutein, vitamin E and / or combinations thereof. In certain embodiments, the animal food composition further comprises EPA / DHA, taurine, lutein, vitamin E and / or combinations thereof. In some embodiments, the animal food composition further comprises a protein source.

[0216] In certain embodiments, the animal food composition comprises a glycyrrhizin source. In certain embodiments, the animal food composition comprises a glycyrrhizin source and a curcuminoid. In certain embodiments, the animal food composition comprises a glycyrrhizin source and linoleic acid. In certain embodiments, the animal food composition comprises a glycyrrhizin source and EPA / DHA. In certain embodiments, the animal food composition comprises a glycyrrhizin source and taurine. In certain embodiments, the animal food composition comprises a glycyrrhizin source and lutein. In certain embodiments, the animal food composition comprises a glycyrrhizin source and vitamin E. In certain embodiments, the animal food composition comprises a glycyrrhizin source, a curcuminoid, and linoleic acid. In certain embodiments, the animal food composition comprises a glycyrrhizin source, a curcuminoid, and EPA / DHA. In certain embodiments, the animal food composition comprises a glycyrrhizin source, a curcuminoid, and taurine. In certain embodiments, the animal food composition comprises a glycyrrhizin source, a curcuminoid, and lutein. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, curcuminoids, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, linoleic acid, and EPA / DHA. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, linoleic acid, and taurine. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, linoleic acid, and lutein. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, linoleic acid, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, EPA / DHA, and taurine. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, EPA / DHA, and lutein. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, EPA / DHA, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, taurine, and lutein. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, taurine, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, lutein, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, curcuminoids, linoleic acid, and EPA / DHA. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, curcuminoids, linoleic acid, and taurine. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, curcuminoids, linoleic acid, and lutein. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, curcuminoids, linoleic acid, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, curcuminoids, linoleic acid, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, curcuminoids, EPA / DHA, taurine, and lutein.In certain embodiments, the animal food composition comprises a source of glycyrrhizin, a curcuminoid, EPA / DHA, taurine, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, a curcuminoid, linoleic acid, EPA / DHA, taurine, and lutein, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, a curcuminoid, linoleic acid, EPA / DHA, taurine, and lutein, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, a curcuminoid, linoleic acid, EPA / DHA, taurine, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, a curcuminoid, linoleic acid, EPA / DHA, taurine, lutein, and vitamin E. In certain embodiments, the animal food composition comprises a source of glycyrrhizin, a curcuminoid, linoleic acid, EPA / DHA, taurine, lutein, and vitamin E.

[0217] In a specific embodiment, the animal food composition of the present disclosure comprises licorice in an amount providing a daily amount of about 0.02 mg / kg to about 2 mg / kg body weight of glycyrrhizin. In certain embodiments, the animal food composition further comprises about 0.01 g / Mcal to about 10 g / Mcal of curcuminoids, about 1 g / Mcal to about 20 g / Mcal of linoleic acid, about 0.1 g / Mcal to about 7 g / Mcal of EPA / DHA, about 1 g / Mcal to about 2 g / Mcal of taurine, about 0.001 g / Mcal to about 0.002 g / Mcal of lutein, about 0.2 g / Mcal to about 0.3 g / Mcal of vitamin E, or a combination thereof.

[0218] In a specific embodiment, the animal food composition of the present disclosure comprises licorice in an amount providing a daily amount of about 0.02 mg / kg to about 1 mg / kg body weight of glycyrrhizin. In certain embodiments, the animal food composition further comprises about 0.01 g / Mcal to about 5 g / Mcal of curcuminoids, about 10 g / Mcal to about 20 g / Mcal of linoleic acid, about 0.1 g / Mcal to about 3 g / Mcal of EPA / DHA, about 1 g / Mcal to about 1.5 g / Mcal of taurine, about 0.001 g / Mcal to about 0.0015 g / Mcal of lutein, about 0.2 g / Mcal to about 0.25 g / Mcal of vitamin E, or a combination thereof.

[0219] In a specific embodiment, the animal food composition of the present disclosure comprises licorice in an amount providing a daily amount of at least about 0.02 mg / kg body weight of glycyrrhizin. In certain embodiments, the animal food composition further comprises about 8 g / Mcal to about 12 g / Mcal of linoleic acid, about 1 g / Mcal to about 2 g / Mcal of EPA / DHA, about 1 g / Mcal to about 2 g / Mcal of taurine, about 0.001 g / Mcal to about 0.002 g / Mcal of lutein, about 0.2 g / Mcal to about 0.3 g / Mcal of vitamin E, or a combination thereof.

[0220] In a specific embodiment, the animal food composition of the present disclosure comprises licorice in an amount providing a daily amount of at least about 0.02 mg / kg body weight of glycyrrhizin. In certain embodiments, the animal food composition further comprises about 10 g / Mcal to about 12 g / Mcal of linoleic acid, about 1.25 g / Mcal to about 1.75 g / Mcal of EPA / DHA, about 1 g / Mcal to about 1.5 g / Mcal of taurine, about 0.001 g / Mcal to about 0.0015 g / Mcal of lutein, about 0.2 g / Mcal to about 0.25 g / Mcal of vitamin E, or a combination thereof.

[0221] In a specific embodiment, the animal food composition of the presently disclosed subject matter comprises licorice in an amount providing a daily amount of at least about 0.02 mg / kg body weight of glycyrrhizin, about 10.5 g / Mcal of linoleic acid, about 1.5 g / Mcal of EPA / DHA, about 1.2 g / Mcal of taurine, about 0.0013 g / Mcal of lutein, and about 0.244 g / Mcal of vitamin E.

[0222] In certain embodiments, the animal food composition further comprises a protein source, a crude fat source, a fiber source, a NFE source, a carbohydrate source, a starch source, or a combination thereof.

[0223] In certain embodiments, the animal is a canine. In a particular embodiment, the canine is a dog. In certain embodiments, the animal food composition comprises or consists of a dry, wet and / or semi-moist food composition.

[0224] The subject matter of the present disclosure also provides a kit as described herein. The kit comprises:

[0225] (i) a first part comprising a glycyrrhizin source; and

[0226] (ii) a second part comprising one or more additional ingredients;

[0227] Method for preventing and / or treating inflammatory diseases or disorders, allergic inflammatory skin diseases, wherein the kit is formulated to provide a daily amount of at least about 0.02 mg / kg body weight of glycyrrhizin to an animal. In certain embodiments, the kit comprises glycyrrhizin and one or more additional ingredients disclosed herein.

[0228] In some embodiments, the glycyrrhizin source may contain at least one of the Glycyrrhiza plants, preferably the root of Glycyrrhiza glabra, i.e., licorice. In some embodiments, the glycyrrhizin source is licorice. In a specific embodiment, the glycyrrhizin source in the kit includes a licorice root extract.

[0229] In a specific embodiment, the kit comprises dry, wet and / or semi-wet food compositions. In certain embodiments, the kit comprises a nutritionally complete animal food composition, a food supplement or a topper composition. In some embodiments, the kit comprises a kibble. In one embodiment, the kit is formulated for oral administration. In one embodiment, the kit comprises a food supplement and / or a drug.

[0230] 6.2.5. Dog breeds and feeding guidelines

[0231] The present disclosure relates particularly to methods for assessing the health and well-being of animals. Characteristics of companion animals may vary by size, sex, breed, and species. Given that domestic animals receive the majority of veterinary care, trends and individual animal characteristics studied for the most common domestic animals (e.g., dogs) can often indicate the efficacy of the methods studied when applied to other animals.

[0232] The present disclosure is particularly directed to methods for determining oral biometrics of animals of the genus Canis. The genus Canis includes domestic dogs (Canis lupus familiaris), wolves, coyotes, foxes, jackals, dingoes, and the present disclosure can be used for all of these animals. In some embodiments, the subject is a domestic dog, referred to herein simply as dog. The genus Canis is part of the family Canidae, which includes many existing species.

[0233] As used herein, the expression "body type category" refers to the definition of an animal (e.g., dog, cat, etc.) according to the average weight of a particular animal breed. Animals of the same breed (e.g., dog, cat, etc.) may have relatively consistent physical characteristics, such as body shape, coat color, physiology, and behavior, compared to animals of different breeds. It is worth noting that the discussion below focuses on dogs, however, other companion animals and wild animals are intended to be included within the scope of the present disclosure, and the present disclosure is not intended to be limited to dogs.

[0234] The dog can be any breed of dog, including a toy breed, a small breed, a medium breed, a large breed, or a giant breed. Non-limiting examples of toy breeds include monkeys, Australian Silky Bichon Frise, Bolognese, Cavalier King Charles Spaniel, Chihuahua, Chinese Crested, Cotton-veiled Terrier, English Toy Brussels Griffon, Havanese, Italian Greyhound, Japanese Spaniel, Cavalier King Charles Spaniel, Lowchen, Maltese, Miniature Pinscher, Papillon, Pekingese, Pomeranian, Pug, Russian Toy Terrier and Yorkshire Terrier Examples of small breeds include, but are not limited to, French bulldogs, beagles, dachshunds, Pembroke Welsh corgis, miniature schnauzers, Cavalier King Charles spaniels, Shih Tzus, and Boston Terriers. Examples of medium-sized dog breeds include, but are not limited to, bulldogs, cocker spaniels, shetland sheepdogs, border collies, basset hounds, Siberian huskies, dalmatians, doberman pinschers, staffordshire bull terriers, and Examples of large dog breeds include, but are not limited to, bearded collies, Great Danes, Neapolitan mastiffs, Scottish deerhounds, Dogue de Bordeaux, Newfoundlands, English mastiffs, Saint Bernards, Lambeaux and Irish wolfhounds. Hybrids can generally be classified as toy dogs, small dogs, medium dogs and large dogs based on their weight. In some embodiments, the dog is a toy breed. In some embodiments, the dog is a medium, large or giant breed. In some embodiments, the dog is a mix of two or more breeds. In this case, the mixed breed dog can still be classified by size based on its weight and may exhibit characteristics associated with each of the two or more breeds found in the dog (e.g., behavioral characteristics, genetic characteristics, etc.).

[0235] The World Canine Federation (Fédération Cynologique Internationale) currently recognizes 346 purebred dog breeds. A dog's breed can be identified, for example, by observing the dog's physical characteristics or by genetic analysis. A purebred dog is the offspring of two dogs of the same breed and is eligible to be registered with a recognized club or association that has a register of dogs of that breed. Many purebred dog registration systems exist, the most famous of which is the Kennel Club in the UK.

[0236] Table 1.

[0237]

[0238] In certain embodiments, the dog's body size category is selected according to Salt et al., 2017 (Table 1) (Salt et al., 2017. Growth standard charts for monitoring bodyweight in dogs of different sizes PLoS ONE 12:e0182064.). In other embodiments, the dog's body size category is selected according to an alternative designation. Small breeds can correspond to animals with an average weight of about 6.5 kg to about 9 kg. Medium breeds can correspond to animals with an average weight between about 9 kg and about 30 kg. Large breeds can correspond to animals with an average weight between about 30 kg and about 40 kg. Large breeds can correspond to animals with an average weight of more than about 40 kg.

[0239] In other embodiments, the size category of the dog is selected according to an alternative designation. Small breeds may correspond to animals with an average weight of up to about 10 kg. Medium breeds may correspond to animals with an average weight of about 10 kg to about 25 kg. Large breeds may correspond to animals with an average weight of about 25 kg to about 45 kg. Giant breeds may correspond to animals with an average weight of at least about 45 kg.

[0240] As is well known, the daily amount of food fed to an animal may depend on the animal's weight. This is particularly true for dogs. The recommended daily amount of food may be provided in Table 2.

[0241] Table 2.

[0242] Body type category name Recommended daily amounts of food Small About 30g to about 200g Medium About 100g to about 400g Large About 200g to about 600g Giant About 360g to about 900g

[0243] In specific embodiments, the amount of glycyrrhizin is from about 5 mg / kg to about 100 mg / kg body weight, from about 10 mg / kg to about 75 mg / kg body weight, from about 15 mg / kg to about 50 mg / kg body weight, or from about 20 mg / kg to about 45 mg / kg body weight, based on the total weight of the dry matter of the animal food composition.

[0244] Therefore, a person skilled in the art can easily determine the amount or amount range (by weight) of glycyrrhizin that should be included in the food composition to provide the preferred daily amount of glycyrrhizin disclosed herein to animals (e.g., canines, especially dogs), for example, expressed as a daily amount of glycyrrhizin per kg body weight.

[0245] Illustratively, to prevent and / or treat allergic skin diseases (e.g., atopic dermatitis) in a small dog weighing 9 kg, 180 g of a complete food composition (e.g., in the form of kibble) is provided daily, wherein the amount of glycyrrhizin contained therein should exceed about 0.27 (0.03 x 9) mg. Thus, the complete food should contain more than about 0.15 mg of glycyrrhizin per 100 g of complete food or about 0.015 mg of glycyrrhizin per kg of complete food.

[0246] As previously described herein, an animal food composition comprising glycyrrhizin can include a food supplement composition (ie, an incomplete food composition) or a complete food composition.

[0247] 6.3. Methods of Preparing Animal Food Compositions

[0248] The subject matter of the present disclosure also includes a method of making the animal food composition specified herein.The process for making the described animal food composition can be carried out according to any method known in the art.

[0249] The animal food composition can be made by mixing the raw materials together and kneading to make a consistent dough or minced meat (i.e., mixture) that can be cooked. This also applies to liquids in which the ingredients are mixed and homogenized before the cooking step in the package. The process of making dry food is usually completed by baking and / or extrusion. The dough is usually sent to a machine called an expander and / or an extruder, which uses pressurized steam or water to cook the raw materials. In the extruder, the dough is under extreme pressure and high temperature. The dough is then pushed through a die (a hole of a specific size and shape) and then cut with a knife. The puffed dough piece is made into a coarsely ground food by passing it through a dryer to reduce moisture to a specified target to ensure the stability of the food before consumption. The coarsely ground food can then be sprayed with fat, oil, minerals, vitamins, natural extract mixtures, palatants, and optionally sealed in a package.

[0250] The composition may be a dry food, a wet food or a semi-moist food as described in the presently disclosed subject matter.

[0251] Thus, the presently disclosed subject matter provides a method of making an animal food composition comprising a source of glycyrrhizin, comprising the steps of:

[0252] a) preparing a glycyrrhizin source;

[0253] b) optionally mixing one or more additional ingredients and / or additives to provide a mixture; and

[0254] c) optionally heating the mixture.

[0255] In non-limiting embodiments, the animal food composition produced by the manufacturing method includes kibble and / or comprises a protein source.

[0256] In certain embodiments, the glycyrrhizin source is mixed with a component selected from the group consisting of a curcuminoid source, a linoleic acid source, an EPA / DHA source, a taurine source, a lutein source, a vitamin E source, and combinations thereof in step b).

[0257] In certain embodiments, the glycyrrhizin source is mixed in step b) with a component selected from the group consisting of a linoleic acid source, an EPA / DHA source, a taurine source, a lutein source, a vitamin E source, and combinations thereof.

[0258] In an embodiment, the glycyrrhizin source is mixed with a component selected from the group consisting of a linoleic acid source, an EPA / DHA source, a taurine source, a lutein source, a vitamin E source, a protein source, a crude fat source, a fiber source or a combination thereof in step b).

[0259] 6.4 Therapeutic applications

[0260] The presently disclosed subject matter provides for the use of an animal food composition as described herein for preventing and / or treating inflammatory diseases or disorders, allergic inflammatory skin diseases, preferably for preventing and / or treating atopic dermatitis, including atopic dermatitis in canines, particularly dogs.

[0261] As discussed herein, allergic inflammatory skin diseases can include at least one of atopic dermatitis, flea allergy dermatitis, urticaria, insect bite allergy, angioedema, inhalation allergy, inhalation allergic dermatitis, food allergy dermatitis, contact dermatitis, miliary dermatitis, eosinophilic granuloma, head and neck pruritus, and generalized pruritus, preferably atopic dermatitis, including atopic dermatitis in canines (particularly dogs).

[0262] In certain embodiments, the animal food composition is used in a method of preventing and / or treating an animal suffering from an inflammatory disease or disorder, an allergic inflammatory skin disease, and more particularly an animal suffering from atopic dermatitis (ie, canine atopic dermatitis).

[0263] In a specific embodiment, the animal food composition is used to prevent and / or treat atopic dermatitis. According to another embodiment, the animal food composition is used to prevent and / or treat canine atopic dermatitis. According to yet another embodiment, the animal food composition is used to reduce the dosage and frequency of medications required to manage an inflammatory disease or disorder or an allergic inflammatory skin condition.

[0264] The presently disclosed subject matter also includes a method of preventing and / or treating an inflammatory disease or condition, an allergic inflammatory skin disease in an animal, comprising at least the step of feeding the animal with an animal food composition according to the presently disclosed subject matter.

[0265] In certain embodiments, the animal suffers from an allergic inflammatory skin disease, preferably, the animal suffers from atopic dermatitis, more preferably, the animal is a dog suffering from canine atopic dermatitis.

[0266] The animal food compositions described herein can prevent or treat inflammatory diseases or conditions, allergic inflammatory skin diseases, preferably atopic dermatitis. In certain embodiments, animals are fed only with the food compositions described herein. In certain embodiments, animals are fed partially with the composition food described herein and another food composition. In certain embodiments, the food composition is fed to animals as a supplementary food or medicine. In any of these disclosed schemes, beneficial effects are obtained.

[0267] In certain embodiments, "partially" means that the animal food composition makes up at least about 30% of the animal's diet, preferably at least about 30% of the animal's diet, even at least about 70% of the animal's diet, even at least about 80% of the animal's diet, even at least about 90% of the animal's diet.

[0268] Typically, food is provided to animals, particularly dogs, every day. In certain embodiments, the animal food composition disclosed herein can be provided to the animal to be treated as the only nutritionally complete food during treatment. According to these embodiments, the nutritionally complete animal food composition is provided to the animal every day during treatment.

[0269] In certain embodiments, the animal food compositions described herein may be provided to the animal to be treated alternately with another animal food composition, preferably another nutritionally complete animal food composition, which may be selected from known animal food compositions, including various commercial animal food compositions, particularly various commercial dog food compositions.

[0270] In a specific embodiment, the animal food composition is provided every other day, thus providing it on a schedule of every two days. In certain embodiments, the animal food composition is provided on a schedule of every three, four, five, six, seven or more days.

[0271] It should be understood that in the daily practice of feeding animals, especially dogs, animal owners cannot always feed animals with animal food compositions every day. In certain embodiments, when animals are fed with the animal food compositions described herein every other day, the beneficial effects of preventing or treating inflammatory diseases or disorders, allergic inflammatory skin diseases, and in particular preventing or treating canine allergic dermatitis can be fully exerted. In specific embodiments, feeding animals every three, four, five, six or seven days will result in reduced beneficial effects, which may require longer treatment times.

[0272] Without being bound by any particular theory, in certain embodiments, highly effective prevention or treatment of inflammatory diseases or disorders, allergic inflammatory skin diseases (e.g., fully effective prevention or treatment of canine allergic dermatitis) requires providing the animal food composition described herein to animals, particularly dogs, at least every other day, and most preferably every day.

[0273] The period of time over which the animal food composition described herein is fed can range from a few weeks to several years, depending primarily on the severity of the allergic inflammatory skin disease (ie, atopic dermatitis).

[0274] As already explained in the present disclosure, a short period of treatment (ie 1 month) is sufficient to reduce itching.

[0275] In certain embodiments, the animal food composition is provided to the animal to be treated over a longer period of time, e.g., over a period of 9 months or longer; e.g., over a period of 12 months or longer, or (i) according to a feeding schedule comprising providing the animal (particularly a dog) with only an animal food composition described herein, or (ii) according to a schedule that alternates providing an animal food composition described herein with another animal food composition.

[0276] The present disclosure also relates to a method of preventing and / or treating an inflammatory disease or condition, an allergic inflammatory skin disease, in an animal suffering from an allergic inflammatory skin disease, comprising at least the step of providing a feeding recommendation comprising an animal food composition as defined in the presently disclosed subject matter.

[0277] The present disclosure also relates to the use of a glycyrrhizin source in preparing a composition for treating allergic inflammatory skin diseases.

[0278] In certain embodiments, the animal food composition inhibits the release of one or more interleukin targets by activated T cells. As described herein, overexpression of interleukin 4 (IL-4) and / or interleukin 5 (IL-5) can indicate that the immune response is prone to an allergic phenotype. In certain embodiments, the animal food composition inhibits the release of IL-5 by activated T cells. In certain embodiments, the animal food composition inhibits the release of IL-4 by activated T cells. In specific embodiments, the animal food composition inhibits the release of IL-5 and IL-4 by activated T cells. In alternative embodiments, the animal food composition does not stimulate the proliferation or release of interleukin 2 (IL-2).

[0279] In certain embodiments, the animal food composition can be used to inhibit the release of I-L4 or IL-5 by activated T cells. In certain embodiments, the animal food composition can be used to prevent and / or treat diseases characterized by increased IL-4 or IL-5 released by activated T cells. In a specific embodiment, the disease characterized by increased IL-4 or IL-5 released by activated T cells is selected from the group consisting of allergic inflammatory skin diseases, in particular, selected from the group consisting of: atopic dermatitis, flea allergy dermatitis, urticaria, insect bite allergy, angioedema, inhalation allergy, inhalation allergic dermatitis, food allergy dermatitis, contact dermatitis, miliary dermatitis, eosinophilic granuloma, head and neck itching, and systemic itching. In a specific embodiment, the disease characterized by increased IL-4 or IL-5 released by activated T cells is atopic dermatitis.

[0280] The presently disclosed subject matter also includes a kit comprising a source of glycyrrhizin for use in a method of preventing and / or treating an inflammatory disease or condition, an allergic inflammatory skin disease, preferably atopic dermatitis (ie, canine atopic dermatitis).

[0281] The present disclosure also relates to the use of a kit for preparing a composition for treating allergic inflammatory skin diseases, the kit comprising a first part and a second part, the first part comprising a glycyrrhizin source, the second part comprising one or more additional ingredients.

[0282] In certain embodiments, the presently disclosed subject matter relates to a kit comprising a source of glycyrrhizin for use in a method of preventing and / or treating an inflammatory disease or disorder, an allergic inflammatory skin disease, wherein the kit is formulated to provide a daily amount of at least about 0.02 mg / kg body weight of glycyrrhizin to an animal.

[0283] In certain embodiments, the kits described herein may be provided to the animal to be treated alternately with another animal food composition or kit, preferably another nutritionally complete animal food composition or kit, which may be selected from known animal food compositions, including various commercial animal food compositions, particularly various commercial dog food compositions.

[0284] In a specific embodiment, the kit is provided every other day, thus providing it according to a schedule of every two days. In certain embodiments, the kit is provided according to a schedule of every three days, four days, five days, six days or seven days.

[0285] The kits described herein are used in methods for preventing or treating inflammatory diseases or conditions, allergic inflammatory skin diseases, preferably atopic dermatitis. In certain embodiments, the animals are fed only with the kits described herein. In certain embodiments, the animals are fed in part with the kits described herein and another food composition or kit. In certain embodiments, the kits are fed to animals as supplementary food or medicine. In any of these disclosed schemes, beneficial effects are obtained.

[0286] 7. Examples

[0287]

[0046] For purposes of understanding and not limitation, the presently disclosed subject matter will be better understood by reference to the following examples, which are provided as illustrations of the presently disclosed subject matter and not by way of limitation.

[0288] Example 1: Safety Study of Glycyrrhizin

[0289] Materials and methods

[0290] The purpose of this clinical trial was to demonstrate the safety of feeding dogs three doses of glycyrrhizin (Gly) in the form of licorice root extract for 28 days, a dose that is much higher than the recommended dose for animal consumption, particularly dogs.

[0291] Dogs. The study included 16 privately owned healthy adult dogs, both male and female. Specifically, the dogs were beagles, Brittany spaniels, or dachshunds weighing between 5kg and 21kg. Twelve of the dogs were female and four were male. A larger number of females was chosen for the study because previous studies in other species have shown that female animals are more likely to experience an increase in blood pressure after exposure to glycyrrhizin.

[0292] Source of glycyrrhizin. The source of glycyrrhizin was provided by a licorice root extract containing 12% glycyrrhizin by weight, formulated in a gelatin capsule. The licorice root extract was purchased from Naturex (Avignon, France) under the product number DAB40178. The product was provided with a certificate of analysis, which showed 12.6% glycyrrhizin by HPLC (high performance liquid chromatography).

[0293] Commercially available pharmaceutical grade gelatin capsules (Capsuline (Capsuline Corporation, Dania Beach, FL, USA) were filled with an accurate weight mixture of licorice powder and 100% pure maltodextrin powder (Bulk Powders, Colchester, UK). The weighed combination of licorice powder and maltodextrin powder was prepared in such a way that, when mixed together and placed in capsules, it provided a daily glycyrrhizin dose for dogs on a schedule of 0.2 mg / kg body weight (Bwt) / day, then 0.4 mg / kg Bwt / day, then 0.6 mg / kg Bwt / day.

[0294] Dosage. The dose to be administered to each dog was calculated based on five different weight groups. Capsules were weighed separately for each group. Licorice root extract was mixed with maltodextrin so as to provide the same volume of total powdered material to each dog. The capsules were placed in wet pet food pellets and fed to the dogs.

[0295] In total, dogs were fed three different doses of glycyrrhizin, each for 28 days. These doses were 0.2 mg / kg Bwt / day, 0.4 mg / kg Bwt / day, and 0.6 mg / kg Bwt / day.

[0296] Each dog has gone through the following protocol cycle, which is repeated for each test concentration. The dosage of the first cycle is 0.2 mg glycyrrhizic acid (Gly) / kg Bwt / day. The dosage of the second cycle is 0.4 mg Gly / kg Bwt / day. The dosage of the third cycle is 0.6 mg Gly / kg Bwt / day.

[0297] Program cycle:

[0298] Day 1: Baseline measurements were taken: blood pressure, and blood and urine concentrations of potassium, sodium, and calcium, creatinine, and aldosterone.

[0299] Day 0: Licorice administration was initiated (the concentration of glycyrrhizin was adjusted based on the first, second, or third cycle of the protocol, as described above). One dose was provided to each dog daily at breakfast.

[0300] Days 1-27: Provide each dog with one dose daily at breakfast.

[0301] Days 2, 4, 7, 14, 21, and 28: Blood pressure and blood and urine concentrations of potassium, sodium, and calcium, creatinine, and aldosterone were measured.

[0302] Day 28: Washout began and the dogs were returned to a separate maintenance diet, i.e., they were no longer fed licorice. The washout period lasted two weeks. Blood pressure and blood and urine potassium, sodium and calcium, creatinine and aldosterone concentrations were measured again on days 34 and 41.

[0303] If the dog's measurements at the end of the period have changed significantly from the baseline measurements, the study is terminated. If the dog's measurements at the end of the period have not changed significantly from the baseline measurements, they proceed to the next period of the protocol.

[0304] Protocol details. Licorice root extract was administered sequentially at the glycyrrhizin (Gly) concentrations given in each cycle of the protocol: 0.2 mg / kg Bwt / day, 0.4 mg / kg Bwt / day, and 0.6 mg / kg Bwt / day. The second and third cycles of the protocol were initiated only after demonstrating that the previous cycle did not result in significant changes in blood pressure (BP) or blood and urine parameters.

[0305] Blood pressure is measured multiple times for each animal, with the first reading discarded. Blood pressure is measured by the oscillometric method. At each measurement, if the dog's mean blood pressure is shown to have risen to a potentially harmful level (usually >160 mmgHg), the dog may be removed from the study (temporarily or permanently) at the discretion of the veterinarian. All dogs are habituated to the oscillometric device and the blood pressure (BP) measurement procedure prior to the start of the study. If there is evidence of stress in any dog ​​before or during the BP procedure, the procedure will be stopped for that dog and restarted once the dog has calmed down. Temporary intensive habituation training may be given to the dog if necessary. If these measures fail to resolve the problem, the dog will be permanently removed from the study and replaced with a closely matched replacement animal. Typical blood pressure ranges for the 3 breeds used are known and taken into account when judging whether BP measurements are normal during the study. For the 3 breeds used, the normal reference ranges for BP are:

[0306] Beagle: Systolic 140 + / - 15, Diastolic 79 + / - 13

[0307] Dachshund: Systolic 142 + / - 10, Diastolic 85 + / - 15

[0308] Brittany Spaniel: Systolic 131 + / - 16, Diastolic 74 + / - 14

[0309] The conditions for BP measurement were carried out according to the following procedure.

[0310] The environment is secluded and quiet. The patient is sedated and allowed to acclimate to the measurement room for 5-10 minutes before attempting a measurement. The animal is then gently restrained in a comfortable position, preferably in ventral or lateral recumbency, to limit the vertical distance from the base of the heart to the cuff. The cuff width is approximately 30%-40% of the circumference of the cuff site. The size of the cuff is tracked and the same size is used each time. The cuff is placed on the right foreleg and the probe is pre-clamped on the right foreleg. This makes the day of collection less stressful and time-pressured. The right foreleg is used for each measurement for all animals. Whenever possible, blood pressure measurements are performed by the same person on the same dog each time.

[0311] Only measure when the patient is calm and motionless. Discard the first measurement. Record a total of 5 consecutive consistent values. In some patients, the measured blood pressure tends to decrease as the measurement progresses. Continue to measure these animals until the decrease stabilizes, and then record 5 consecutive consistent values.

[0312] Repeat blood pressure measurements as needed, changing cuff position as necessary to obtain consistent values. Blood pressure values ​​are based on the average of the 5 recorded measurements.

[0313] A small blood sample (4 ml) was collected on the date indicated in the protocol description above to determine the potassium, sodium and calcium, creatinine and aldosterone concentrations in the blood. Urine (at least 3 ml) was collected freely every day as described above to determine the concentrations of potassium, sodium and calcium in the urine. Urine creatinine concentration was also measured so that the excretion fractions (Fractional Excretion Rate, FER) of sodium, potassium and calcium could be calculated.

[0314] FER is calculated according to the following equation:

[0315] (urine potassium x serum creatinine x 100) / serum potassium x urine creatinine).

[0316] Since licorice root extract (LRE) / Gly was evaluated as a single ingredient, it was most effective to administer the measured amount of licorice directly in the capsule. Therefore, the appropriate dose of LRE was weighed into gelatin capsules and then administered according to the dog's normal feeding schedule.

[0317] Statistics: The effect of diet (glycyrrhizin dose) was assessed using a linear mixed model. Animals were modeled as random terms. Alpha correction for multiple comparisons was performed using Tukey HSD. The significance level for two-sided tests was set at 5%.

[0318] Two approaches to blood pressure modeling were evaluated. In the first approach, the difference in blood pressure between baseline and 4 weeks was calculated for each dog and each series and set as the dependent variable. In the second approach, blood pressure after 4 weeks was used as the dependent variable, while blood pressure at baseline was included as a covariate in the model.

[0319] result

[0320] Blood Pressure. Table 3 below provides the overall mean systolic blood pressure (mmHg) over time for each tested dose of glycyrrhizin (Gly):

[0321] Table 3.

[0322] average value Day 0 Day 2 Day 4 Day 7 Day 14 Day 21 Day 28 0.2mg Gly 120 127 125 126 126 122 121 0.4mg Gly 118 117 119 125 122 120 124 0.6mg Gly 125 119 123 125 123 124 122

[0323] These results indicate that there were no significant differences in blood pressure between day 0 and any subsequent time points for any dose tested.

[0324] Potassium fractional excretion. Table 4 below provides the overall mean potassium fractional excretion over time for each dose of glycyrrhizin (Gly) tested. The results are expressed as a percentage of potassium excreted in the urine compared to the amount of potassium filtered and retained by the kidneys.

[0325] Table 4.

[0326] average value Day 0 Day 2 Day 4 Day 7 Day 14 Day 21 Day 28 0.2mg Gly 16.54 15.74 15.59 15.06 13.33 20.02 16.54 0.4mg Gly 16.02 15.56 16.02 15.72 16.87 16.09 16.27 0.6mg Gly 16.48 18.08 17.48 13.15 15.64 14.93 16.48

[0327] These results indicate that there were no significant differences in fractional potassium excretion between day 0 and any subsequent time points at any dose tested.

[0328] Plasma Aldosterone Concentrations. Table 5 below provides the overall mean plasma aldosterone concentrations (in pmol / L) over time for each tested dose of glycyrrhizin (Gly):

[0329] Table 5.

[0330] average value Day 0 Day 7 Day 14 Day 28 0.2mg Gly 62.13 45.13 49.75 44.83 0.4mg Gly 54.00 52.25 56.38 70.57 0.6mg Gly 36.50 42.57 59.00 63.25

[0331] These results indicate that there were no significant differences in plasma aldosterone concentrations between day 0 and any subsequent time points at any dose tested.

[0332] In conclusion, based on the results of this study, glycyrrhizin had no significant effects on blood pressure homeostasis, fractional potassium excretion, and plasma aldosterone concentrations in adult dogs at the doses and durations tested.

[0333] Example 2: Immunomodulatory potential of glycyrrhizin

[0334] Materials and methods

[0335] Licorice root extract preparation for bioassay. Licorice root extract (LRE) was obtained from William Ransom & Son PLC (UK). During preparation, 20 g of root powder was suspended in 100 ml of 20% ethanol in distilled water. The suspension was then heated to 60°C for 2 hours under moderate agitation, and the resulting extract was then filtered through Whatman No. 4 filter paper. The extraction process was repeated again with the filtered solid material. The pooled filtrate was then concentrated in a rotary evaporator at 40°C overnight to produce a paste extract. Fresh phytochemical extracts were stored at -20°C under nitrogen. According to the supplier's specifications, the glycyrrhizin concentration of the extract was 18% w / w. The concentration of LRE was based on the wet weight of the extract. All assays were performed using the same extract.

[0336] Licorice root extract was weighed and suspended in dimethyl sulfoxide (DMSO - Sigma, UK) at 100 mg / mL and then further diluted to 4 mg / mL in complete tissue culture medium (CTCM; RPMI-1640 medium (Sigma) plus fetal bovine serum (Sigma) to 5%, 2 mM L-glutamine (Sigma), 100 U / mL penicillin and 100 μg / mL streptomycin (Sigma). These stock solutions were further diluted in CTCM to give final concentrations in the assay wells between 0.3 μg / mL and 1000 μg / mL.

[0337] Human peripheral blood mononuclear cells (HuPBMC) were isolated. HuPBMC were isolated using the method of Telford et al. (Telford et al., International Immunopharmacology 4 (2004) 1455-1466). In short, heparinized blood was obtained with the consent of healthy human volunteers aged 20-50 years (Nottingham University School of Medicine Research Ethics Committee, BT / 04 / 2005), diluted in an equal volume of RPMI-1640 medium (Sigma), and layered on Histopaque 1077 (Sigma). After centrifugation at 710xg for 20 minutes, the buffy coat was harvested and washed twice with RPMI-1640. The cells were suspended in CTCM at 106 / mL. The mononuclear cell concentration was 85% as determined by cytology.

[0338] Cytotoxicity of LRE on Jurkat E6.1 T cell line and HuPBMC. Cytotoxicity was assessed using the human T lymphocytic leukemia Jurkat E6.1 cell line (Walsh et al., 2008). 5 Pre-diluted LRE extracts were tested in triplicate at final concentrations ranging from 0.3 μg / mL to 1000 μg / mL in 200 μL CTCM of Jurkat E6.1 cells. Cell viability was assessed by counting 10 random fields of the objective reticle under a microscope using the dye exclusion method (20 μL 0.4% trypan blue (Sigma, UK) in saline) after incubation for 24 hours at 37°C in 5% CO2. Survival was determined by comparison with control incubations of cells without LRE.

[0339] Similar cytotoxicity assays as above were performed using normal, fresh human peripheral blood mononuclear cells. The same pre-diluted extracts were tested in triplicate over the range of 0.1 μg / ml to 1000 μg / ml and 10 5 HuPBMCs were incubated together for 24 h at 37°C in 5% CO2. Cell viability was assessed using trypan blue dye exclusion as described previously. Survival was determined by comparison with cells incubated in the absence of LRE.

[0340] Proliferation and cytokine release assays of HuPBMCs. Anti-CD3 antibody (BD Pharmingen, UK) combined with anti-CD28 antibody (BD Pharmingen, UK) was used to stimulate HuPBMC T cell proliferation and cytokine expression to evaluate the regulatory effects of liquorice extract. Cell proliferation was determined by [3H]-thymidine incorporation. All in vitro assays were performed with 6 replicates.

[0341] In a 96-well U-bottom plate, each well contains 10 5 Pre-diluted root extract (LRE) was tested in 200 μL CTCM of 1000 μg / mL HuPBMC cells at final concentrations ranging from 0.3 μg / mL to 1000 μg / mL. The assay used suboptimal levels of anti-CD3 and anti-CD28 (final assay concentration of each was 100 ng / mL). Suboptimal stimulation can be used to determine potential stimulatory and inhibitory effects. Dexamethasone alone was also tested in triplicate at a final concentration of 0.5 μM as a positive control (maximum immunosuppression). DMSO alone was tested as a vehicle control.

[0342] For interleukin-2 determination, 50 μ culture medium was taken out from each well after incubation for 24 hours at 37° C. in 5% CO2 and stored at -20° C. until IL-2 concentration was analyzed. At this point, cells were pulsed with 0.25 μCi / well [3H] thymidine (GE Healthcare (General Electric Healthcare), UK) and incubated for another 24 hours, then harvested onto GF / c filter plates (Packard (Packard), UK) using a PackardFiltermate collector. Radioactivity retained on the filter was determined using a PackardTopcount NXT scintillation counter, and EC50 (effective concentration that reduces proliferation by 50%) was determined by nonlinear regression using Prism 3.0 software. For the remaining cytokine determinations, 150 μL culture medium (followed by harvesting cells) was taken out from each well after incubation for 48 hours at 37° C. in 5% CO2 and stored at -20° C., followed by IL-2, IL-5, IL-17 and IFN-γ analysis.

[0343] Cytokine analysis. The concentrations of IL-2, IL-5, IL-17 and IFN-γ in the conditioned medium were determined by ELISA according to the following protocol: 50 μL of the relevant capture antibodies (BD Pharmingen, UK; aIL-2, 555051; aIL-5, 55493; aIFN-y, 551221; aIL-17, 560486) were coated with 1 μg / mL in a carbonate / bicarbonate buffer at pH 9.6 in a 96-well assay plate (Nunc, UK) and incubated overnight at 4°C. The wells were then incubated with 200 μL of 1% bovine serum albumin (BSA, Sigma, UK) in phosphate-buffered saline (PBS) for 1 hour at room temperature, followed by washing three times with PBS+0.05% Tween 20 (Sigma, UK). 50 μL of cell culture supernatant samples were then diluted in an equal volume of PBS / tween+1% BSA. Prepared samples and cytokine standards (human, BD Pharmingen, UK: IL-2, 555602; IL-5, 554606; IFN-γ, 554616; IL-17 Sigma, H7791) were added to the relevant wells. After incubation at 4°C overnight, the wells were washed three times with PBS / tween and incubated with 50 μL of the relevant biotinylated detection antibody (human, BD Pharmingen, UK: αIL-2, 555040; αIL-5, 554491; αIFN-γ, 554550; IL-17, 555067) at 0.5 μg / mL in PBS / tween + 1% BSA added to each well for 1 hour at room temperature. The washed plates were incubated with 50 μL / well 1:1000 streptavidin / peroxidase (BD Pharmingen, UK) in PBS / tween + 1% BSA for 30 min at room temperature and, after a final wash with PBS / tween, incubated with 100 μL / well 0.1 mg / mL tetramethylbenzidine substrate (Sigma, UK) in 0.1 M acetate buffer, pH 6. The reaction was stopped by adding 20 μL 2M H2SO4 and the plates were read at 450 nm on a Dynex MRX plate reader.

[0344] Statistical analysis. For cytokine assays, LRE concentrations were compared to anti-CD3 / CD28 stimulation controls only. One-way ANOVA followed by Dunnett's post-test was used to determine whether JMP14 significantly inhibited cell survival, proliferation, and cytokine secretion. For Dunnett post hoc comparisons, reference data were provided by stimulation-only positive control incubations.

[0345] result

[0346] Cytotoxicity of Licorice Root Extract on Jurkat E6.1 T Cell Line and Human PBMC. Jurkat E6.1 cells have been previously used to evaluate the potential immunotoxicity of compounds (Walsh et al., Marine Drugs. 6 (2008) 291-307). This provides a useful method to determine whether LREs are able to induce cell stress / death in monocytes within the concentration range used in subsequent immunomodulatory experiments. Licorice root extract was not toxic to the Jurkat cell line at concentrations up to 100 μg / ml ( Figure 1 At 300 μg / ml, there was evidence of cytotoxicity with approximately 30% cell death (p<0.01), which increased to 40% at 1 mg / ml of extract (p<0.01). In conclusion, 100 μg / ml of extract was the maximum safe concentration acceptable for interpretation of immunocytometry assays.

[0347] Similar toxicity assays using HuPBMC cells yielded similar results ( Figure 1 At an extract concentration of 300 μg / ml, cell viability was again reduced (p<0.01), although there was no further reduction at 1 mg / ml, the results further confirm that the maximum interpretable extract concentration for the cell assay is 100 μg / ml.

[0348] Anti-CD3 / CD28 stimulated HuPBMC proliferation and interleukin-2 release. The proliferation of HuPBMC populations was measured in the presence of LRE. The effect of LRE was evaluated in the range of 0.3 μg / ml-1000 μg / ml while CD3 / CD28 stimulation ( Figure 2 ). There was no evidence of an effect in the range of 0.3 μg / ml-30 μg / ml LRE. Proliferation was reduced by approximately 40% at 100 μg / ml. Thus, proliferation was affected when LRE concentrations were below the cytotoxic threshold.

[0349] Interleukin-2 (IL-2) is a key cytokine produced by activated T cells and plays a role in controlling immune cell development and proliferation. Therefore, it can be used as an indicator of the activation state of monocyte populations. When evaluated in a T cell activation model, there was no evidence that IL-2 release was affected by LRE in a concentration range of 0.3 μg / ml-100 μg / ml ( Figure 2 ). However, IL-2 secretion was reduced by approximately 30% at 300 μg / ml LRE and further reduced by 10% at 1000 μg / ml LRE.

[0350] Summarizing these observations, there is evidence that LRE has cytotoxic effects at concentrations of 300 μg / ml and above. However, the proliferative response was more sensitive to the extract at a concentration of 100 μg / ml, which resulted in a significant reduction (p<0.05). Interleukin-2 secretion did not appear to be as sensitive to LRE as cell proliferation, with 300 μg / ml being the first concentration to cause a significant reduction (p<0.05). However, the effects at higher concentrations were less dramatic.

[0351] Two possible explanations for the observations at high LRE concentrations are that the antiproliferative and anti-IL-2 effects are simply related to cell stress / death and may be indicators of early cell stress that can be detected before cell death sets in. Alternatively, the antiproliferative and anti-IL-2 effects may be distinct from cell death.

[0352] Stimulated HuPBMCs expressed interleukin-5, interleukin-17, and interferon-γ. To further elucidate the potential immunomodulatory effects of LRE, and in particular to determine its effects on different helper T (Th) cell types, titrated concentrations of the extract were incubated with anti-CD3 / CD28 activated HuPBMCs. Th1 cell activity was inferred by quantifying interferon-γ secretion in the culture medium.

[0353] Similarly, Th2 activity was measured by quantifying the proxy interleukin 5. Finally, Th17 activity was inferred by measuring interleukin-17 (IL-17). Figure 3 Immunomodulatory effects were assessed by comparing cytokine secretion to that observed in the presence of activator (human anti-CD3 / CD28) alone, thus calibrating to 100% activity.

[0354] In the HuPBMC assay, LRE concentrations between 0.1 μg / ml and 10 μg / ml did not significantly reduce the secretion of either interferon-γ (IFNγ) or IL-17. However, at 3 μg / ml and 10 μg / ml, interleukin-5 secretion was significantly reduced, by 30% (P<0.05) and 40% (P<0.005), respectively, compared with the positive control. The reduction was greater at 30 μg / ml, by >50% (P<0.0001) compared with the positive control, and at 100 μg / ml, by 75% (P<0.0001). At LRE concentrations above 100 μg / ml, the expression of all 3 cytokines was significantly inhibited compared with the positive control (P<0.0001). At these higher concentrations, the effects observed may be related to the cytotoxicity of LRE. Thus, at concentrations below 100 μg / ml, the different effects on cytokines are explained. The 100 μg / ml concentration is somewhat ambiguous as an effect on proliferation was observed. At concentrations above 100 μg / ml, cytotoxicity may explain all observations. A summary of the different effects of LRE on the three cytokines is shown in the results in the figures described above.

[0355] in conclusion

[0356] In summary, the inventors have provided evidence that aqueous extracts of licorice root can inhibit the release of IL-5 from activated T cells within a concentration range that is non-cytotoxic and does not stimulate proliferation or IL-2 release. This concentration range also has no significant effect on the Th-1 cytokine IFN-γ and the Th-17 cytokine IL-17.

[0357] ***

[0358] Although the subject matter of the present disclosure and its advantages have been described in detail, it should be understood that various changes, substitutions and variations can be made herein without departing from the spirit and scope of the disclosed subject matter. In addition, the scope of the present application is not intended to be limited to the specific embodiments of the process, material composition, method and process described in the specification. As will be readily understood by those of ordinary skill in the art from the disclosure of the subject matter of the present disclosure, according to the subject matter of the present disclosure, the process, material composition, method or process of performing the function substantially the same as the corresponding embodiment described herein or realizing substantially the same result that currently exists or will be developed thereafter can be utilized. Therefore, the appended claims are intended to include such process, material composition, method or process within their scope.

[0359] For various patents, patent applications, publications, product descriptions, protocols, and sequence accession numbers cited in this application, the disclosures of which are incorporated herein by reference in their entirety for all purposes.

Claims

1. An animal food composition comprising a glycyrrhizin source for use in a method for preventing and / or treating an inflammatory disease or condition, or an allergic inflammatory skin disease, wherein: The animal food composition is formulated to provide the animal with glycyrrhizin in an amount of at least about 0.02 mg / kg body weight per daily amount.

2. The animal food composition for use according to claim 1, wherein: The animal food composition is formulated to provide the animal with glycyrrhizin in an amount of about 0.02 mg / kg body weight to about 2 mg / kg body weight per day.

3. The animal food composition for use according to claim 1 or 2, wherein: The animal food composition is formulated to provide the animal with a daily amount of glycyrrhizin in an amount of about 0.03 mg / kg to about 2 mg / kg body weight, particularly about 0.05 mg / kg to about 1 mg / kg body weight, particularly about 0.1 mg / kg to about 0.8 mg / kg body weight, particularly about 0.2 mg / kg to about 0.6 mg / kg body weight.

4. The animal food composition for use according to any one of claims 1 to 3, wherein: The animal food composition is selected from the group consisting of a nutritionally complete animal food composition, a food supplement, and a covering composition.

5. The animal food composition for use according to any one of claims 1 to 4, wherein: The glycyrrhizin source includes licorice root extract.

6. An animal food composition for use according to any one of the preceding claims, wherein The composition also includes linoleic acid.

7. An animal food composition for use according to any one of the preceding claims, wherein The composition further comprises EPA / DHA, taurine, lutein, vitamin E and / or combinations thereof.

8. An animal food composition for use according to any one of the preceding claims, wherein The allergic inflammatory skin disease is selected from the group consisting of atopic dermatitis, flea allergy dermatitis, urticaria, insect bite allergy, angioedema, inhalation allergy, inhalation allergic dermatitis, food allergy dermatitis, contact dermatitis, miliary dermatitis, eosinophilic granuloma, head and neck pruritus and generalized pruritus.

9. A kit, comprising: (I) a first part comprising a glycyrrhizin source; and (ii) a second part comprising one or more additional ingredients; Use in a method for preventing and / or treating allergic inflammatory skin diseases, wherein the kit is formulated to provide glycyrrhizin in an amount of at least about 0.02 mg / kg body weight per day to an animal.

10. An animal food composition comprising a glycyrrhizin source, wherein: The amount of glycyrrhizin is at least about 5 mg / kg based on the total weight of dry matter of the animal food composition.

11. The animal food composition according to claim 10, wherein The amount of glycyrrhizin is from about 5 mg / kg to about 100 mg / kg based on the total weight of dry matter of the animal food composition.

12. The animal food composition according to claim 10 or 11, wherein The amount of glycyrrhizin is about 5 mg / kg to 100 mg / kg, particularly about 10 mg / kg to 75 mg / kg, particularly about 15 mg / kg to 50 mg / kg and particularly about 20 mg / kg to 45 mg / kg, based on the total weight of dry matter of the animal food composition.

13. The animal food composition according to any one of claims 10 to 12, wherein The animal food composition includes kibble and / or the animal food composition further comprises a protein source.

14. The animal food composition according to any one of claims 10 to 13, wherein The animal food compositions include nutritionally complete food compositions.

15. The animal food composition of any one of claims 10 to 14 or the kit of claim 9, formulated for oral administration.

16. The animal food composition according to claims 10 to 15 or the kit according to claim 9 or 15, wherein The glycyrrhizin source consists of licorice root extract.

17. An animal food composition according to any one of claims 10 to 16, further comprising one or more additional ingredients.

18. The animal food composition according to claim 17 or the kit according to claim 9, 15 or 16, wherein The one or more additional ingredients are selected from linoleic acid, EPA / DHA, taurine, lutein, vitamin E and / or combinations thereof.

Images