Food compositions for treating chronic inflammatory joint diseases
A novel food composition with a balanced EPA:DHA ratio and additional ingredients addresses the limitations of conventional treatments by enhancing inflammation resolution, effectively reducing pain and improving mobility in companion animals with chronic joint diseases.
Patent Information
- Application Number
- PCT/EP2025/059783
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-04-10
- Filing Date
- 2025-04-09
- Publication Date
- 2025-10-16
AI Technical Summary
Conventional treatments for chronic inflammatory joint diseases in companion animals, such as osteoarthritis, often rely on suppressing inflammation with NSAIDs, which can cause side effects and have limited efficacy, while there is a need for compositions that promote the resolution of inflammation to alleviate pain and improve well-being.
A novel food composition with a specific EPA:DHA mass ratio, ranging from 0.2:1 to 1:1, and total amounts of EPA and DHA from 0.1 g/Mcal to 20 g/Mcal, along with optional ingredients like curcuminoids and hydrolyzed collagen, to enhance the resolution of inflammation and treat chronic joint diseases in canines and felines.
The composition effectively enhances the resolution of inflammation, reducing pain, improving mobility, and addressing symptoms like allodynia and central sensitization in companion animals by activating specialized pro-resolving mediators, thus providing a more effective treatment than traditional anti-inflammatory approaches.
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Abstract
Description
FOOD COMPOSITIONS FOR TREATING CHRONIC INFLAMMATORY JOINT DISEASESCROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to European patent application no. EP 24169528.7, filed on April 10, 2024, which is incorporated herein by reference in its entirety.FIELD OF THE DISCLOSURE
[0002] The present disclosure relates to the field of food compositions for companion animals, particularly canines or felines. In particular, the present disclosure relates to food compositions, such as nutritionally complete food compositions or functional complements, and methods for treating chronic inflammatory joint diseases in companion animals such as dogs or cats.BACKGROUND OF THE DISCLOSURE
[0003] Chronic inflammatory diseases affecting the joints, particularly osteoarthritis (OA), pose significant challenges in canine and feline health. Osteoarthritis is a degenerative inflammatory joint condition characterized by the breakdown of joint cartilage and underlying bone, leading to symptoms such as joint pain, stiffness, and reduced mobility. The progression of osteoarthritis is associated with an imbalance in joint metabolism, leading to cartilage degradation and subsequent pain, inflammation, and sensitization.
[0004] In cats, the prevalence of osteoarthritis is remarkably high, with radiographic evidence indicating its presence in up to 61% of cats aged six years or older, and in 90% of cats aged twelve years or older.
[0005] While the progression of symptoms in cats is often gradual over the course of several years, it can significantly impact their quality of life. In addition to osteoarthritis, various chronic joint diseases involving inflammation can afflict cats, necessitating effective treatment options.
[0006] Inflammation is known to be an essential defence mechanism for preserving health and plays a vital role in the regeneration of injured tissues. While inflammation can be uncomfortable, it is a necessary response to tissue damage and pathogens. A weak inflammatory response can lead to tissue destruction. In contrast,uncontrolled or excessive inflammation can lead to a lot of different diseases including cardiovascular, metabolic, inflammatory diseases, such as joints, or even cancers (Hwang et al. Int J Mol Sci. 2019; Dalli et al. Blood. 2012). Nonresolving inflammation is now acknowledged as a major driver in most of these diseases. A failure in the resolution of inflammation can lead to chronic inflammatory disease (Schett et al. Nat Common. 2018).
[0007] In the context of chronic joint diseases in dogs and cats, such as osteoarthritis, the inflammatory response plays a complex role. Osteoarthritis is believed to be primarily caused by mechanical stress on the joints, leading to a low- grade chronic inflammation within the affected joint. This chronic inflammation contributes to the degradation of joint cartilage, resulting in pain, inflammation, allodynia and central sensitization.
[0008] Conventional treatments for chronic inflammatory joint diseases, including osteoarthritis, often focus on suppressing inflammation through the use of medications like Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). NSAIDs can induce a lot of gastro-intestinal side effects (impact on renal function or gastro-intestinal side effects) specially in cats. Some NSAIDs have a limited effect on cats suffering from osteoarthritis specially cats with allodynia (Guillot et al. Vet J. 2013).
[0009] Therefore, it seems essential to address and resolve the chronic inflammatory processes associated with osteoarthritis to effectively manage the disease.
[0010] Recent advancements in the understanding of chronic inflammation have highlighted the importance of the resolution phase of inflammation. Resolution of inflammation is an active process that aims to restore tissue homeostasis and promote healing. Specialized pro-resolving mediators (SPMs), such as lipoxins, maresins, resolvins, and protectins, are involved in resolving inflammation by dampening the inflammatory response, promoting tissue repair, and stimulating the clearance of inflammatory cells and debris. Defects in the resolution of inflammation can lead to prolonged and dysregulated inflammation, contributing to the progression of chronic inflammatory diseases.
[0011] In the case of chronic joint diseases in dogs and cats, promoting the resolution of inflammation may be a more effective approach than simply suppressing inflammation. By addressing the underlying mechanisms that hinder the resolution phase of inflammation, it may be possible to modulate the chronic inflammatoryresponse associated with osteoarthritis, reduce tissue damage, and promote tissue repair.
[0012] Therefore, there is a general need for evidence-based food compositions which are efficient for treating or preventing chronic inflammatory joint diseases in companion animals, particularly in canines or felines.
[0013] In particular, there is a need for novel food composition to treat or prevent chronic inflammatory joint diseases in companion animals, such as canines or felines, particularly osteoarthritis, to alleviate pain, reduce inflammation, and improve the overall well-being of companion animals, particularly of canines or felines.
[0014] There is also a need for novel food compositions suitable for the resolution of the acute and chronic inflammation in companion animals, particularly canines or felines.
[0015] The present disclosure has for purpose to satisfy all or part of the above- mentioned needs.SUMMARY OF THE DISCLOSURE
[0016] The present disclosure provides a novel food composition including a particular EPA:DHA mass ratio, which has been designed to treat or prevent chronic inflammatory joint diseases in companion animals, particularly canines or felines.
[0017] Thus, a first aspect of the present disclosure relates to a food composition including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal in need thereof, particularly a canine or a feline, wherein the mass ratio of EPA to DHA is from about 0.2:1 to about 1 :1 , preferably from about 0.3:1 to about 0.9:1 , and the total amount of EPA and DHA is from about 0.1 g / Mcal to about 20 g / Mcal.
[0018] An embodiment of the present disclosure relates to a nutritionally complete and balanced food composition including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal in need thereof, wherein the mass ratio of EPA to DHA is from about 0.2:1 to about 1 :1 , preferably from about 0.3:1 to about 0.9:1 , and the total amount of EPA and DHA is from about 0.1 g / Mcal to about 20 g / Mcal.
[0019] An embodiment of the present disclosure relates to a nutritionally complete and balanced feline food composition including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for use in a method for treating and / or preventing a chronic inflammatory joint disease in a feline in need thereof, wherein the mass ratio of EPA to DHA is from about 0.2:1 to about 1 :1 , preferably from about 0.3:1 to about 0.9:1 , and
[0020] the total amount of EPA and DHA is from about 0.1 g / Mcal to about 20 g / Mcal.An embodiment of the present disclosure relates to a functional complement including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal in need thereof, particularly a canine or a feline in need thereof, wherein the mass ratio of EPA to DHA is from about 0.2:1 to about 1 :1 , preferably from about 0.3:1 to about 0.9:1 , and the total amount of EPA and DHA is from about 0.1 g / Mcal to about 20 g / Mcal.
[0021] This food composition, as described herein, offers the advantage of not just suppressing but enhancing the resolution process generated by the chronic inflammatory joint disease. This stands in contrast to current anti-inflammation solutions, which only aim to suppress inflammation.
[0022] The resolution of inflammation involves resolution factor molecules, called Specialized ProResolving Mediators (SPMs) (Gilroy et al. Nat Rev Drug Discov. 2004; Serhan et al. J Exp Med. 2000; Serhan et al. Nat Immunol. 2005). SPMs actively terminate the inflammatory process and lead to the recovery of homeostasis by blocking leukocyte trafficking, reversing vasodilation and vascular permeability, and promoting the clearance of inflammatory cells, exudates, and tissue debris (Hwang et al. Int J Mol Sci. 2019; Serhan et al. FASEB J. 2017). With the improvement of laboratory method (LC-MS / MS for the lipidomics dosage of SPM and endocannabinoids) it is now possible to detect those mediators, to obtain a complete lipid mediator profile and to measure the impact of nutrients / ingredients on their production.
[0023] Endocannabinoids are defined as endogenous lipids able to activate CB1 or CB2 cannabinoid receptors. They can be co-6-derived endocannabinoids or co-3- derived endocannabinoids, co-3-derived endocannabinoids, like DHEA and EPEA, demonstrate beneficial effects in nociceptive and inflammatory -pain and neuropathic pain (Paton et al. Eur J Pain. 2020 ; Tyrtyshnaia et al. I nt J Mol Sci. 2021).
[0024] It is demonstrated in the example section of the present disclosure the direct correlation between the management of SPMs and the metabolism of EPA and DHA.
[0025] Specifically, it is shown that a food composition with a higher weight proportion of DHA than EPA can lead to a most important activation of the SPMs for the resolution of the inflammation in cats and dogs having osteoarthritis. DHA activates SPMs pathways such as 17 HDOHE, RVD5, 14 HDOHE, Maresins 1 and Maresin 2, known to have effects on various components of osteoarthritis and pain, including allodynia (Valdes et al. Sci Rep. 2017; Huang et al. Arthritis Rheumatol. 2017). In parallel, it is demonstrated that the level of EPA can be sufficient to enhance inflammation resolution by activating SPMs pathways such as 18 HEPE, RVE1 and RVE2, known as well for their efficiency in managing pain. Before the profiling of the fatty acid, a fat extraction needs to be performed. This extraction can be done with different methods (for example by cold extraction with isopropanol / hexane or by hydrolysis). The choice of fat extraction can induce some variability. The preferred option is extraction by hydrolysis. Then, the fatty acids characterization is performed by gas chromatography.
[0026] Thus, an advantage of the food composition as described herein can rely in its capacity to resolve the inflammation of a companion animal, particularly a canine or a feline, affecting with a chronic inflammatory joint disease.
[0027] A further advantage of the food composition as described herein can rely in its capacity to treat and / or prevent a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline.
[0028] In some embodiments, the food composition for use as described herein can include from about 1 .6 mg / Mcal to about 4400 mg / Mcal of curcuminoids.
[0029] In some embodiments, the food composition for use as described herein can include from about 0.07 g / Mcal to about 215 g / Mcal of hydrolysed collagen.
[0030] In some embodiments, the curcuminoids can be selected from, without limitation, curcumin, demethoxycurcumin, bisdemethoxycurcumin and / or tetrahydrocurcumin.
[0031] In some particular embodiments, the curcuminoids can be curcumin.
[0032] In some embodiments, the hydrolyzed collagen can comprise a combination of at least glycine, proline and hydroxyproline.
[0033] In some embodiments, the food composition for use as described herein can include from about 0.05 g / Mcal to about 10 g / Mcal of EPA.
[0034] In some embodiments, the food composition for use as described herein can include from about 0.05 g / Mcal to about 5 g / Mcal of EPA.
[0035] In some embodiments, the food composition for use as described herein can include from about 0.05 g / Mcal to about 3 g / Mcal of EPA.
[0036] In some embodiments, the food composition for use as described herein can include from about 0.05 g / Mcal to about 19 g / Mcal of DHA.
[0037] In some embodiments, the food composition for use as described herein can include from about 0.05 g / Mcal to about 17 g / Mcal of DHA.
[0038] In some embodiments, the food composition for use as described herein can include from about 0.2 g / Mcal to about 10 g / Mcal of DHA.
[0039] In some embodiments, the food composition for use as described herein can include from about 0.2 g / Mcal to about 5 g / Mcal of DHA.
[0040] In some embodiments, the food composition for use as described herein can include from about 0.5 g / Mcal to about 10 g / Mcal of EPA and DHA.
[0041] In some embodiments, the food composition for use as described herein can include from about 0.5 g / Mcal to about 6 g / Mcal of EPA and DHA.
[0042] In some embodiments, a source of EPA and DHA can be selected from, without limitation, fish oil, fish meal, algae oil (macro and micro), vegetal GMO, precision fermentation biomass (yeast or bacteria), eggs, oyster, chia seed, walnuts, soybeans, Green Lipped Mussel or a mixture thereof.
[0043] In some embodiments, the chronic inflammatory joint disease can be selected from, without limitation, osteoarthritis, bursitis, rheumatoid arthritis, juvenile rheumatoid arthritis, infectious arthritis, psoriasis-related arthritis or reactive arthritis disease.
[0044] In some particular embodiments, the chronic inflammatory joint disease can be osteoarthritis.
[0045] In some embodiments, the feline can be a cat.
[0046] In some embodiments, the canine can be a dog.
[0047] A further advantage of the food composition as described herein can rely in its capacity to reduce the symptoms of a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, such as the pain and / or difficulties in mobility, such as difficulties in walking.
[0048] A further advantage of the food composition as described herein can be its capacity to reduce symptoms of an allodynic cat having a chronic inflammatory joint disease. A further advantage of the food composition as described herein can be its capacity to reduce symptoms of a central sensitization cat having a chronic inflammatory joint disease.
[0049] In some embodiments, the companion animal can exhibit signs of central sensitization, signs of allodynia and / or signs of hyperalgesia.
[0050] Thus, in some embodiments, the dog or the cat can be a dog or a cat with signs of central sensitization and / or with signs of allodynia.
[0051] In some embodiments, the food composition can be a dry food composition including at least about 2500 kilocalories of metabolizable energy (ME) per kilogram.
[0052] In some embodiments, the food composition can be a wet food composition including at least about 400 kilocalories of metabolizable energy (ME) per kilogram.
[0053] According to a further aspect, the present disclosure relates to a nutritionally complete and balanced food composition including:- Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), wherein the food composition can include from about 0.1 g / Mcal to about 20 g / Mcal of EPA and DHA and wherein the mass ratio of EPA to DHA is from about 0.2:1 to about 1 :1 , and- from about 0.07 g / Mcal to about 215 g / Mcal of hydrolysed collagen.
[0054] According to a further aspect, the present disclosure relates to a method for feeding a companion animal, particularly a canine or a feline, optionally a feline in need thereof, wherein the method includes at least a step of administering to the companion animal a food composition according to the present disclosure.BRIEF DESCRIPTION OF THE FIGURES
[0055] Figure 1 depicts a graph illustrating the temporal evolution of Night-time actimetry monitoring (NAM) in percentage of change versus Baseline for the cats in Cohort 1 (in black) and the cats in Cohort 2 (in grey). Ordinate: Total NAM mean expressed in percentage of change versus BLS mean. Abscissa: Time of the test in weeks (W).
[0056] Figure 2 depicts a histogram illustrating the means results (SD) of the alteration score, expressed in %, measured with the MI-CAT(V) overtime for the cats inCohort 1 (in black) and the cats in Cohort 2 (in grey). Ordinate: Means results of the alteration score expressed in percentage, measured in the osteoarthritis cats. Abscissa: Time of the measurement expressed in weeks at BSL (Week 0), W4 (week 4), W8(week 8), W12 (week 12), and W16 (week 16).
[0057] Figure 3 depicts a graph illustrating the relative marginal means of the most affected hindlimb Peak Vertical Force (PVF) for the cats in Cohort 1 (in black) and the cats in Cohort 2 (in grey). Ordinate: Most affected hindlimb Peak Vertical Force.Abscissa Time of the test expressed in weeks (W).
[0058] Figure 4 depicts a graph illustrating the result of the stairs assay compliance improvement overtime for the cats in Cohort 1 (in black) and the cats in Cohort 2 (in grey). Ordinate: Percentage of cats presenting a stair improvement overtime. Abscissa: Time of the test expressed in weeks (W).
[0059] Figure 5 depicts a histogram illustrating the mean result of the assay measuring the time for a cat to climb up per passage overtime for the cats in Cohort 1 (in black) and the cats in Cohort 2 (in grey). Ordinate: Mean time for each cohorts to climb up per passage expressed in seconds. Abscissa: Time of the test expressed in weeks (W).
[0060] Figure 6 depicts a graph illustrating the results of the alteration score measured with MI-CAT(V) (expressed in % of change versus baseline) overtime for the cats in Cohort 6 (in black) and the cats in Cohort 7 (in grey). Ordinate: Mean of the alteration score MI-CAT(V) expressed in percentage of change versus baseline, measured in the OA cats. Abscissa: Time of the measurement expressed in days at BSL (D 0), D6 (day 6), D63 (day 63), D74 (day 74), and D81 (day 81 ).
[0061] Figure 7 depicts Evolution of the MI-CAT(V) score presented in percentage of change vs baseline (BSL) (cohort 6 in black, cohort 7 in grey).
[0062] Figure 8 shows descriptive data of daytime actimetry monitoring (DAM - 50th percentile count) over time of cohort 14 (n=20 in black) and cohort 15 (n=20 in grey).
[0063] Figure 9 shows Daytime actimetry monitoring (DAM - 50th percentile count) over time of cohort 14 (in black) and cohort 15 (in grey). Data are presented as least-squares means ± 95% confidence intervals.# inter-group significant difference (P < 0.05) a, b intra-group significant difference: different letters indicate a significant within-time difference (P < 0.05).
[0064] Figure 10 shows evolution of most affected hind limb Peak Vertical Force (kg ■ s ■ cm-1) over time of cohort 14 (in black) and cohort 15 (in grey), following a normalization by the dog’s velocity. Model-based marginal mean value for each acquisition sessions.# inter-group significant difference (P < 0.05) a, b intra-group significant difference: times who don’t share similar letters indicate a significant within-time difference (P < 0.05).
[0065] Figure 11 shows evolution of most affected hind limb Peak Vertical Force (kg ■ s ■ cm-1) over time of cohort 14 (in black) and cohort 15 (in grey), following a normalization by the dog’s velocity. Model based marginal mean values expressed relatively (%) to the baseline mean.DETAILED DESCRIPTION OF THE DISCLOSURE
[0066] The present disclosure provides a novel food composition including a particular EPA:DHA mass ratio, which has been designed to treat and / or prevent a chronic inflammatory joint disease in companion animals, particularly canines or felines. This food composition, as described herein, offers the advantage of not just suppressing but enhance the resolution process generated by a chronic inflammatory joint disease. This stands in contrast to current anti-inflammation solutions, which only aim to suppress inflammation.Definitions
[0067] The terms used in this disclosure generally have their ordinary meanings in the art, within the context of this disclosure and in the specific context where each term is used. Certain terms are discussed below, or elsewhere in the specification, to provide additional guidance in describing the compositions and methods of the disclosure and how to make and use them.
[0068] Exemplary methods and food compositions are described below, although methods and food compositions similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.
[0069] Numeric ranges are inclusive of the numbers defining the range. The headings provided herein are not limitations of the various aspects of the disclosure.Accordingly, the terms defined immediately below are more fully defined by reference to the specification in its entirety.
[0070] All publications and other references mentioned herein are incorporated by reference in their entirety.
[0071] As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. The terms "a" (or "an"), as well as the terms "one or more," and "at least one" can be used interchangeably herein. In some aspects, the term "a" or "an" means "single." In other aspects, the term "a" or "an" includes "two or more" or "multiple." Thus, for example, reference to “a source of an ingredient” can include a mixture of at least two sources of an ingredient.
[0072] As used herein, "and / or" is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term "and / or" as used in a phrase such as "A and / or B" herein is intended to include "A and B," "A or B," "A" (alone), and "B" (alone). Likewise, the term "and / or" as used in a phrase such as "A, B, and / or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).
[0073] The term “about”, as used herein, means within an acceptable error range for the particular value as 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. In general, the term “about” can modify a numerical value above and below the stated value by a variance of, for instance, 10 percent, up or down (higher or lower). In some embodiments, the term indicates deviation from the indicated numerical value by ±15%, ±10%, ±5%, ±4%, ±3%, ±2%, or ±1%.
[0074] As used herein, the terms “comprise”, “comprising”, “include”, “including” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a food composition, a process or a method that includes or comprises a list of nutriments, ingredients, or steps which does not include only those nutriments, ingredients, or steps but can include other nutriments, ingredients, or steps not expressly listed or inherent to such food composition, process or method. The term “consisting of” implies the inclusion of the stated element(s), to the exclusion of any additional nutriments, ingredients, or steps. The term “consisting essentially of” implies the inclusion of the stated elements, and possibly other element(s) where theother element(s) do not materially affect the basic and novel characteristic(s) of the disclosure. It is understood that the different embodiments of the disclosure using the term “including” or equivalent cover the embodiments where this term is replaced with “consisting of” or “consisting essentially of”.
[0075] In the detailed description herein, references to “embodiment,” “an embodiment,” “one embodiment,” “in some embodiments,” or any other variation thereof, indicate that the described embodiment(s) can include a particular nutriments, ingredients, or steps, but every embodiment might not necessarily include the particular nutriments, ingredients, or steps. Moreover, such phrases are not necessarily referring to the same embodiment. Further, when a particular nutriments, ingredients, or steps is described in connection with an embodiment, it is submitted that it is within the knowledge of one skilled in the art to affect such nutriments, ingredients, or steps in connection with other embodiments whether or not explicitly described. After reading the description, it will be apparent to one skilled in the relevant art(s) how to implement the disclosure in alternative embodiments.
[0076] As used herein, the terms “animal” or “companion animal” can be used interchangeably and refer to domesticated animals. In some particular embodiments, a companion animal can refer to a canine and / or a feline. In some particular embodiments, a companion animal can refer to a dog and / or a cat.
[0077] As used herein, the term “canine” encompasses animals, including companion animals selected from recognized dog breeds (some of which are further subdivided), which may can include afghan hound, airedale, akita, Alaskan malamute, basset hound, beagle, Belgian shepherd, bloodhound, border collie, border terrier, borzoi, boxer, bulldog, bull terrier, cairn terrier, chihuahua, chow, cocker spaniel, collie, corgi, dachshund, dalmatian, doberman, English setter, fox terrier, German shepherd, golden retriever, great dane, greyhound, griffon bruxellois, Irish setter, Irish wolfhound, King Charles spaniel, Labrador retriever, lhasa apso, mastiff, newfoundland, old English sheepdog, papillion, Pekingese, pointer, pomeranian, poodle, pug, rottweiler, St. Bernard, saluki, samoyed, schnauzer, Scottish terrier, Shetland sheepdog, shih tzu, Siberian husky, Skye terrier, springer spaniel, West Highland terrier, whippet, Yorkshire terrier, etc.
[0078] As used herein, the term “feline” refers to any animal of the taxonomic family Felidae, characterized by shared physical traits including a compact body, retractable claws, sharp carnivorous teeth, keen senses (particularly vision andhearing), and a flexible muscular structure that enables agility and swift movements. Felines can encompass a diverse range of species, such as cats, like wild cats and domestic cats, lions, tigers, leopards, jaguars, and other big wild cats. In some embodiments, a feline can be a cat, in particular a domestic cat. In some embodiments, a feline may exhibit signs of allodynia, signs of hyperalgesia and / or signs of central sensitization.
[0079] As used herein, the term “allodynia" refers to “pain due to a stimulus that does not normally provoke pain” (definition of the The International Association for the Study of Pain (IASP)).
[0080] As used in herein, the term “hyperalgesia” refers to “increased pain from a stimulus that normally provokes pain ». (definition of the International Association for the study of Pain (IASP)). (Jensen et al. Lancet Neurol. 2014).
[0081] As used herein, the term “central sensitization” represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation (Latremoliere et al. J Pain. 2009 ; Woolf et al. Pain. 2011). As used herein, the term Quantitative Sensory Testing (QST) is a collective term that refers to various domains and approaches of sensory threshold testing: mechanical, pressure, vibration, electrical, and thermal. (Kriek 2023). They are used to quantify somatosensory sensation under normal or pathological conditions in which hypo- or hypersensitivity can occur. (Monteiro et al. Osteoarthritis Cartilage. 2020).
[0082] As used herein, the term “food composition” covers all of foodstuff, diet, food supplement or a material that can sustain growth, repair and vital processes of a cat. Such a food composition can contain one or more ingredients, such as source of nutriments. Nutriments of a food composition can be typically proteins, fibers, carbohydrates and / or fats, which can be used in combination in the body of an organism to sustain growth, repair and vital processes and to furnish energy (defined with the metabolizable energy (ME)). Carbohydrates includes NFE (Nitrogen free extract). A food composition as disclosed herein can also contain supplementary ingredients such as substances or additives, for example, flavoring, minerals and vitamins. A foodcomposition as disclosed herein can further contain a carrier, a diluent, and / or an excipient.
[0083] As used herein, “nutritionally complete and balanced” in the context of a food composition means that the food composition comprises all the essential nutrients in appropriate proportions to meet an animal's dietary requirements for maintaining overall health and well-being. A nutritionally complete and balanced food composition can maintain the body weight of the cat without significant change with the Body Condition Score (BCS). A nutritionally complete and balanced food composition ensures that the animal receives all the necessary nutrients for optimal health, minimizing the risk of nutritional deficiencies or imbalances that could lead to health issues over time. Specifically, a nutritionally complete and balanced food composition can contain all known required nutrients for the intended recipient of the food composition, in all appropriate amounts and proportions based, for example, on recommendations of recognized and competent authorities in the field of feline or canine nutrition, such as the Association of American Feed Control Officials (AAFCO) or the European Pet Food Industry Federation (FEDIAF), for complete and balanced pet nutrition. Therefore, a nutritionally adequate diet is a diet with which said animal can be fed as the sole ration and is capable of sustaining life without additional food (except water). For instance, a nutritionally complete and balanced food composition can contain carbohydrates, proteins, fats, vitamins and minerals, and optionally water.
[0084] As used herein, the term “functional complement” refers to a food composition which provides nutritional components that are important for health maintenance. These food compositions contain compounds that are biologically active or bioavailable, such as probiotics, amino acids, multivitamins, and antioxidants, and often are found to be useful for the treatment of disease and disorders or the maintenance of normal health states. Functional complements are not nutritionally complete food compositions, meaning that a functional complement does not provide the complete and balanced nutritional requirements to a companion animal. Functional complements are generally used in conjunction with another feed to improve the nutritive balance or performance of the total feed and intended to be fed undiluted as an addition to other feeds. As non-limitative examples, it can be mentioned chews, soft chews, tablets, powder, liquid, jelly, etc. The person skilled in the art is well aware of how to prepare a functional complement. As non-limitative example for jellies, it can be mentioned the following products: Vitakraft Jelly Lovers, Premiere by Fressnapf,Vetocanis Agrobiothers laboratoire, Vital Veto, Laboratoire francodex friandise humides.
[0085] In the context of the present disclosure, an "ingredient" or “component” refers to any individual component or substance that is intentionally included in the formulation of a food composition. An ingredient can be of various types, such as a source of proteins, a source of carbohydrates, a source of fats, a source of vitamins, a source of minerals, flavorings, preservatives, and / or other additives. An ingredient can be a raw material, a raw material by-product, an additive and / or a nutritional supplement. The selection and combination of ingredients can be critical in producing a complete and balanced food composition for a cat.
[0086] As used herein “eicosapentaenoic acid” or “EPA” refers to a polyunsaturated fatty acid belonging to the omega-3 family. Chemically, it is a 20-carbon chain with 5 double bonds. The CAS Registry Number® of EPA is 10417-94-4.
[0087] As used herein “docosahexaenoic acid” or “DHA” refers to a polyunsaturated fatty acid belonging to the omega-3 family. Chemically, it is 22 carbon atoms and 6 double bonds, chemically identified as C22:6. The CAS Registry Number® of DHA is 6217-54-5.
[0088] As used herein, the term “curcuminoids” refers to phenols that are primarily found in turmeric, a plant belonging to the ginger family. Turmeric is generally derived from the roots of the plant Curcuma longa. Curcuminoids have also been found in roots of other species in the plant family Zingiberaceae of the Curcuma genus. Curcuminoids can include curcumin, demethoxycurcumin, bisdemethoxycurcumin and / or tetrahydrocurcumin. The chemical structures of curcuminoids differ in their functional groups. In particular, turmeric can contain about 60% to about 80% of curcumin, about 15% to about 30% of demethoxycurcumin and about 2% to about 6% of bisdemethoxycurcumin. Curcuminoids can be found in some naturally-occuring extracts and / or plants, or chemically obtained. A source of curcuminoids can consist of a turmeric extract, i.e., Curcuma Longa. Non-limitative examples of turmeric extract are the turmeric extract BCM-95® from Arjuna or the turmeric extract from Naturex. Any other source of curcuminoids known to a person skilled in the art can also be used. Curcuminoids can be found in other botanicals in addition to Curcuma longa, such as Curcuma xanthorrhiza and Curcuma zedoania. Curcuminoid in its pure form has poor solubility in water. Curcuminoids can be extracted from curcuminoids-containing plants, e.g., turmeric root, with organic solvent such as ethanol or acetone.
[0089] As used herein, the term “hydrolyzed collagen” is referred to as collagen hydrolysate, gelatin, gelatin hydrolysate, hydrolyzed gelatin, and collagen peptides. The amino acid content of hydrolyzed collagen is the same as collagen. Hydrolyzed collagen can contain up to 19 amino acids, predominantly glycine, proline and hydroxyproline, (which together can represent about 50%, or more, of the total amino acid content). In certain embodiments, the hydrolyzed collagen can have a molecular weight in the range of about 1 kD to about 300 kD (Kilodalton). In certain embodiments, the hydrolyzed collagen protein can have a molecular weight of about 10 kD, about 50 kD, about 100 kD, about 150 kD, about 200 kD, about 250 kD or about 300 kD. In certain embodiments, the hydrolyzed collagen can have an average molecular weight of about 10 kD, about 20 kD, about 30 kD, about 40 kD, about 50 kD, about 60 kD, about 70 kD, about 80 kD, about 90 kD or about 100 kD. The process of hydrolysis involves breaking down the molecular bonds between individual collagen strands and peptides using combinations of physical, chemical or biological means. Hydrolyzed collagen is obtained by the enzymatic hydrolysis of collagenous tissues found in the bones, skin, and connective tissue of animals such as cattle, without limitation, fish, horses, pigs, reptiles, and rabbits.
[0090] As used herein the term “providing” includes selling, supplying, administering, or feeding a companion animal, such as a feline.
[0091] As used herein, the term “weight percent” or “wt%” or “by weight” is meant to refer to the quantity by weight of a nutrient or ingredient in a food composition as a percentage on a dry matter basis of the food composition, unless otherwise specified. The specified amount of nutrients or ingredients included in a food composition as described herein represents the amount present in the total quantity of raw materials provided as sources of said nutriments or ingredients for producing the said food composition.
[0092] The expression “dry matter basis” or “DM” must be interpreted as a method of expressing the concentration of a nutrient or an ingredient in a food composition by expressing its concentration relative to its dry matter content (the concentration remaining once the moisture has been taken out). At the opposite, the expression “as fed” must be interpreted as a method of expressing the concentration of a nutrient or an ingredient in a food composition by expressing its concentration in the state it is fed, which includes moisture. It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, canalso be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable sub-combination.
[0093] As used herein, the expression “chronic inflammatory joint disease” or “CIJD” in the context of companion animals, such as canines or felines refers to a pathological condition characterized by persistent and progressive inflammation of companion animal, such as a feline or a canine, joints. This condition manifests as a chronic inflammatory response within the joint tissues, leading to joint lesions, persistent pain, stiffness, decreased mobility, and potential degradation of cartilage and bone. Clinical signs of CIJD in companion animals, such as felines or canines, may include intermittent or persistent lameness, decreased physical activity, reluctance to jump or climb, as well as behavioral changes due to pain. CIJD can encompass several specific conditions such as arthritis, rheumatoid polyarthritis, osteoarthritis, bursitis, rheumatoid arthritis, juvenile rheumatoid arthritis, infectious arthritis, psoriasis-related arthritis or reactive arthritis disease and / or other forms of chronic inflammatory arthropathies. In certain embodiments, a companion animal, such as a feline or a canine, afflicted with a chronic inflammatory joint disease may exhibit signs of allodynia, hyperalgesia and / or central sensitization.
[0094] As used herein, the terms “treating” or “treatment” in the present disclosure refers to the administration of a food composition according to the disclosure with the purpose to treat, alleviate, relieve, alter, remedy, ameliorate, improve, or affect a chronic inflammatory joint disease, the symptoms of a chronic inflammatory joint disease, the likelihood of a chronic inflammatory joint disease, or to prevent or delay the onset of the symptoms, complications, or otherwise arrest or inhibit further development of a chronic inflammatory joint disease in a statistically significant manner. In the context of the present disclosure, “treating” a chronic inflammatory joint disease encompasses the resolution of the chronic inflammation. More particularly, “treating” or “treatment” encompasses any approach for obtaining beneficial or desired results in a companion animal, such as a feline or a canine, afflicted with a chronic inflammatory joint disease. Beneficial or desired clinical results can encompass, but are not limited to, alleviation or amelioration of one or more symptoms or conditions associated with a chronic inflammatory joint disease; diminishment or reduction of the severity of a chronic inflammatory joint disease or symptoms related to a chronic inflammatory joint disease; maintaining the stability (preventing deterioration) of a chronic inflammatory jointdisease; delaying or slowing down the progression of a chronic inflammatory joint disease; minimizing the recurrence of a chronic inflammatory joint disease; and remission, whether partial or total and whether detectable or undetectable. In other words, “treatment” as used herein includes any cure, amelioration, or reduction of a chronic inflammatory joint disease or related symptom. A “reduction” of chronic inflammatory joint disease symptoms of a chronic inflammatory joint disease means decreasing of the severity or frequency of a chronic inflammatory joint disease or symptoms thereof, or elimination of a chronic inflammatory joint disease or symptoms thereof. Symptoms of a chronic inflammatory joint disease in a companion animal, such as a feline or a canine, can include, but is not limit to, pain, allodynia, hyperalgesia, central sensitization, fatigue, weakness, a poor mobility, and / or difficulties with walking.
[0095] As used herein, the terms “prevent” or “preventing” (and grammatical variants thereof) with respect to a chronic inflammatory joint disease relate to prophylactic treatment of a chronic inflammatory joint disease, e.g., in a companion animal, such as a feline or a canine, suspected to have a chronic inflammatory joint disease, or at risk for developing a chronic inflammatory joint disease. Prevention may include, but is not limited to, preventing, or delaying onset or progression of a chronic inflammatory joint disease and / or maintaining one or more symptoms of a chronic inflammatory joint disease at a desired or sub-pathological level. The term “prevent” does not require the 100% elimination of the possibility or likelihood of occurrence of the event. Rather, it denotes that the likelihood of the occurrence of the event has been reduced in the presence of a composition or method as described herein. More particular, “prevent” or “preventing” refers to a decrease in the risk of occurrence of a chronic inflammatory joint disease or symptoms thereof in a companion animal, such as a feline or a canine. As indicated above, the prevention may be complete, i.e., no detectable symptoms or disease, or partial, such that fewer symptoms or less severity of a chronic inflammatory joint disease are observed than would likely occur absent treatment.
[0096] It should be understood that every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this specification will include every higher numerical limitation, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this specification will include every narrower numerical range that fallswithin such broader numerical range, as if such narrower numerical ranges were all expressly written herein.
[0097] All lists of items, such as, for example, lists of ingredients, are intended to and should be interpreted as Markush groups. Thus, all lists can be read and interpreted as items “selected from the group consisting of’ the list of items “and combinations and mixtures thereof.”Units
[0098] As used herein, an amount of a nutrient or an ingredient as expressed as weight per megacalories, such as grams per megacalorie (g / Mcal), consists of a weight amount of the said nutrient or ingredient by unit of Metabolizable Energy (ME) of the food composition.
[0099] 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 present disclosure, the ME value can be measured by any suitable method known in the art.
[0100] Illustratively, the ME value can be measured using feeding trial. In practice, the gross energy (GE) of the food composition is determined in the laboratory, and the amounts of food eaten by the animals are recorded. The feces and urine from the animals are collected, and the energy in each is determined and called fecal energy (FE) and urinary energy (UE), respectively. The ME is then calculated as:ME (kcal / kg) = [GE - (FE + UE)] I Kg of food consumed.
[0101] Alternatively, the ME value can be measured by standard mathematical methods, taking into account, depending on the method, the percentage of crude fat (CF), of crude protein (CP), of NFE (carbohydrates) and / or of Total Dietary Fibers (TDF) in the food composition. In practice each percentage is multiplied by its respective Atwater Factors. The resulting sum is then multiplied by 10. The mathematical method can be represented by the following formula:ME (kcal / kg) = 10 x [(3.5 x CP) + (8.5 x CF) + (3.5 x NFE)].
[0102] In some embodiments, the ME can be determined according to the predictive equation proposed by the National Research Council (NRC) in 2006.
[0103] In a particular embodiment of the disclosure, especially for a cat, the ME, in kcal / 100g, can be calculated as:ME = GE x [95.6 - (0.89 x TDF x 100 / DM) ] / 100) - (0.77 x CP) orME = GE x [87.9 - (0.88 x CF x 100 / DM) ] / 100) - (0.77 x CP) with GE = (5.7 x CP) + (9.4 x CF) + [4.1 x (NFE + CF)]
[0104] In some embodiments, a food composition as disclosed herein can be characterized by its Metabolizable Energy (ME) parameter.
[0105] In some embodiments, a food composition as disclosed herein can be a dry food composition having a Metabolizable Energy (ME) of at least about 2500 kilocalories per kilogram, as measured according to the NRC 2006.
[0106] In some embodiments, a food composition as disclosed herein can be a wet food composition having a Metabolizable Energy (ME) of at least about 400 kilocalories per kilogram, as measured according to the NRC 2006.
[0107] In some embodiments, a food composition as described herein can be a dry food composition, typically having a moisture content ranging from about 4% to about 12% by weight.
[0108] In some embodiments, a dry food composition as described herein can have a Metabolizable Energy (ME) ranging from about 2500 kcal / kg to about 5000 kcal / kg, or from about 2800 kcal / kg to 5000 kcal / kg, or from about 3000 kcal / kg to about 4000 kcal / kg, or from about 3500 kcal / kg to about 4500 kcal / kg or from about 3600 kcal / kg to about 4300 kcal / kg, as measured according to the NRC 2006.
[0109] In some embodiments, a dry food composition as disclosed herein can have a Metabolizable Energy (ME) of about 3600 kcal / kg, or about 3700 kcal / kg, or about 3800 kcal / kg, or about 3900 kcal / kg, or about 4000 kcal / kg, or about 4100 kcal / kg, or about 4200 kcal / kg, or about 4300 kcal / kg, as measured according to the NRC 2006.
[0110] In some embodiments, a food composition as described herein can be a wet food composition, typically having a moisture content ranging from about 50% to about 90% by weight.
[0111] In some embodiments, a wet food composition as described herein can have a Metabolizable Energy ranging from about 400 kcal / kg to about 1600 kcal / kg, or from about 500 kcal / kg to about 1500 kcal / kg, or from about 600 kcal / kg to about 1400 kcal / kg, or from about 700 kcal / kg to about 1200 kcal / kg, as measured according to the NRC 2006.
[0112] In some embodiments, a wet food composition as described herein can have a Metabolizable Energy of about 600 kcal / kg, or about 700 kcal / kg, or about 900 kcal / kg, or about 950 kcal / kg, or about 1000 kcal / kg, or about 1050 kcal / kg, or about 1100 kcal / kg, or about 1150 kcal / kg, or about 1200 kcal / kg, as measured according to the NRC 2006.
[0113] When the amount of nutritional ingredients in a food composition is expressed as a percentage (%), a skilled person can convert it into grams per megacalorie using the following formula: Multiply the percentage of the ingredient as fed by 10, then by 1000, and finally divide by the metabolizable energy (ME) of the food as determined by the NRC 2006. In other words, the formula for converting to grams per megacalorie is: X g / Mcal = (% as fed *10*1000) / ME NRC 2006.
[0114] Alternatively, a skilled person will also be able to convert an amount of ingredient expressed in grams per megacalorie into a percentage with the above formula.
[0115] In some embodiments, particularly for functional complements, it may be more appropriate to express the quantity of components in grams per kilogram of Body Weigh per day (g / kg BW / day).
[0116] The person skilled in the art knows how to convert g / Mcal to g / kg BW / day.
[0117] As an illustration, it is described hereinafter a three-step process to perform this conversion:
[0118] Step 1- > Determine the daily caloric allocation in Kilocalories (Kcal):
[0119] - For a cat, the calculation of the daily caloric allocation is based on the cat’s condition (lean, normal, overweight, or undergoing a weight loss program, etc.), the sexual status (intact or neutered), and the level of activity (inactive or active). Depending on the situation, this coefficient used in this calculation can range from 42 to 93.Daily caloric allocation (Kcal) = coefficient * BW (kg)0-711
[0120] For a dog, the calculation of the daily caloric allocation is based on the dog’s condition (lean, normal, overweight or undergoing a weight loss program, etc.), the sexual status (intact or neutered) and the level of activity (inactive or active). Depending of the situation, this coefficient used in this calculation can range from 60 to 125.Daily caloric allocation (Kcal) = coefficient * BW (Kg)0-75
[0121] Step 2- > Convert into a daily quantity of EPA+DHA, EPA, DHA or Hydrolised Collaqen in qrams (q / day) and Curcuminoids in milliqrams (mq / day)
[0122] To calculate the quantity of EPA+DHA in grams per day: / dav) = (daily caloric allocation (Kcal / dof
[0123] To calculate the quantity of curcuminoids in milligrams per day: ititv of Curcuminoids (mq / dav) = (daily caloric allocation (Kcal / dav)of Curcuminoids
[0124] Step 3- > Convert into a daily quantity of EPA+DHA, EPA, DHA or
[0125] To calculate the quantity of EPA+DHA in grams per kilogram of body weight per day:Quantity of EPA+DHA (q / kq(BW) per day) = Quantity of EPA+DHA (q / per
[0126] To find the quantity of Curcuminoids in milligrams per kilogram of body weight per day:Quantity of Curcuminoids (mg / kq(BW) per day) = Quantity of EPA+DHAThe food composition, for instance the nutritionally complete and balanced food composition
[0127] The present disclosure relates to a food composition including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) with a specific mass ratio and total amount of EPA to DHA.
[0128] A food composition as described herein is intended to be used for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof.
[0129] A food composition as described herein includes EPA and DHA.
[0130] A food composition as described herein can be a nutritionally complete and balanced food composition. A food composition as described herein can be a functional complement. In some embodiments, a food composition as described herein can be a nutritionally complete and balanced feline food composition. In some embodiments, a food composition as described herein can be a nutritionally complete and balanced canine food composition. In some embodiments, a food composition as described herein can be a feline functional complement. In some embodiments, a food composition as described herein can be a canine functional complement.
[0131] In some embodiments, a food composition as described herein can present a mass ratio of EPA to DHA from about 0.2:1 to about 1 :1.
[0132] In some embodiments, a food composition as described herein can present a mass ratio of EPA to DHA from about 0.2:1 to about 0.95:1 , or from about 0.2:1 to about 0.9:1 , or from about 0.2:1 to about 0.85:1 , or from about 0.2:1 to about 0.8:1 , or from about 0.2:1 to about 0.75:1 , or from about 0.2:1 to about 0.7:1 ; or from about 0.25:1 to about 0.95:1 , or from about 0.25:1 to about 0.9:1 , or from about 0.25:1 to about 0.85:1 , or from about 0.25:1 to about 0.8:1 , or from about 0.25:1 to about 0.75:1 , or from about 0.25:1 to about 0.7:1 ; or from about 0.3:1 to about 0.9:1 , or from about 0.3:1 to about 0.8:1 ; or from about 0.35:1 to about 0.95:1 , or from about 0.35:1 to about 0.90:1 , or from about 0.35:1 to about 0.85:1 , or from about 0.35:1 to about 0.80:1 , or from about 0.35:1 to about 0.75:1 , or from about 0.35:1 to about 0.7:1 ; or from about 0.4:1 to about 0.9:1 , or from about 0.4:1 to about 0.85:1 , or from about 0.4:1 to about 0.8:1 , or from about 0.4:1 to about 0.75:1 , or from about 0.4:1 to about 0.7:1 .
[0133] In some embodiments, a food composition as described herein can present a mass ratio of EPA to DHA of about 0.2:1 , or about 0.25:1 , or about 0.3:1 , or about 0.35:1 , or about 0.4:1 , or about 0.45:1 , or about 0.47:1 , or about 0.5:1 , or about0.55:1 , or about 0.6:1 , or about 0.65:1 , or about 0.7:1 , or about 0.75:1 or about 0.8:1 , or about 0.85:1 , or about 0.9:1 .
[0134] The food composition, for instance a nutritionally complete and balanced feline food composition, as described herein includes EPA and DHA wherein the mass ratio of EPA to DHA can be from about 0.2:1 to about 1 :1 and wherein the total amount of EPA and DHA can be from about 0.1 g / Mcal to about 20 g / Mcal.
[0135] In some embodiments, according to the conversion from g / Mcal to g / Kg (BW) per day, described below, the food composition as described herein can include from about 0.0020 to about 2.1022 g / kg (BW) per day of EPA and DHA.
[0136] In some embodiment, the total amount of EPA and DHA of the food composition as described herein can be from about 0.5 g / Mcal to about 10 g / Mcal.
[0137] In some embodiments, according to the conversion from g / Mcal to g / Kg (BW) per day, described below, the food composition as described herein can include from about 0.0100 to about 1 .0511 g / kg (BW) per day of EPA and DHA.
[0138] In some embodiments, the total amount of EPA and DHA of the food composition as described herein can be from about 0.1 g / Mcal to about 20 g / Mcal, or from about 0.1 g / Mcal to about 18 g / Mcal, or from about 0.1 g / Mcal to about 15 g / Mcal, or from about 0.1 g / Mcal to about 13 g / Mcal, or from about 0.1 g / Mcal to about 11 g / Mcal, or from 0.5 g / Mcal to about 15 g / Mcal, or from 0.5 g / Mcal to about 12 g / Mcal, or from about 0.5 g / Mcal to about 10 g / Mcal, or from about 0.5 g / Mcal to about 8 g / Mcal, or from about 0.2 g / Mcal to about 9 g / Mcal, or from about 0.2 g / Mcal to about 7 g / Mcal, or from about 0.25 g / Mcal to about 5 g / Mcal.
[0139] In some embodiments, the total amount of EPA and DHA of the food composition as described herein can be of about 0.1 g / Mcal, or about 0.15 g / Mcal, or about 0.2 g / Mcal, or about 0.25 g / Mcal, or about 0.3 g / Mcal, or about 0.35 g / Mcal, or about 0.4 g / Mcal, or about 0.45 g / Mcal, or about 0.5 g / Mcal, or about 0.55 g / Mcal, or about 0.6 g / Mcal, or about 0.65 g / Mcal, or about 0.7 g / Mcal, or about 0.75 g / Mcal, or about 0.8 g / Mcal, or about 0.85 g / Mcal, or about 0.9 g / Mcal, or about 0.95 g / Mcal, or about 1 g / Mcal, or about 1 .1 g / Mcal, or about 1.15 g / Mcal, or about 1 .2 g / Mcal, or about 1.25 g / Mcal, or about 1.3 g / Mcal, or about 1.35 g / Mcal, or about 1.4 g / Mcal, or about 1 .45 g / Mcal, or about 1 .5 g / Mcal, or about 1 .55 g / Mcal, or about 1 .65 g / Mcal, or about 1.7 g / Mcal, or about 1.75 g / Mcal, or about 1.8 g / Mcal, or about 1.85 g / Mcal, or about 1.9 g / Mcal, or about 1.95 g / Mcal, or about 2 g / Mcal, or about 2.1 g / Mcal, or about 2.15 g / Mcal, or about 2.2 g / Mcal, or about 2.25 g / Mcal, or about 2.3 g / Mcal, or about 2.35g / Mcal, or about 2.4 g / Mcal, or about 2.45 g / Mcal, or about 2.5 g / Mcal, or about 2.55 g / Mcal, or about 2.6 g / Mcal, or about 2.65 g / Mcal, or about 2.7 g / Mcal, or about 2.75 g / Mcal, or about 2.8 g / Mcal, or about 2.85 g / Mcal, or about 2.9 g / Mcal, or about 2.95 g / Mcal, or about 3 g / Mcal, or about 3.1 g / Mcal, or about 3.15 g / Mcal, or about 3.2 g / Mcal, or about 3.25 g / Mcal, or about 3.3 g / Mcal, or about 3.35 g / Mcal, or about 3.4 g / Mcal, or about 3.45 g / Mcal, or about 3.5 g / Mcal, or about 3.55 g / Mcal, or about 3.6 g / Mcal, or about 3.65 g / Mcal, or about 3.7 g / Mcal, or about 3.75 g / Mcal, or about 3.8 g / Mcal, or about 3.85 g / Mcal, or about 3.9 g / Mcal, or about 3.95 g / Mcal, or about 4 g / Mcal, or about 4.1 g / Mcal, or about 4.15 g / Mcal, or about 4.2 g / Mcal, or about 4.25 g / Mcal, or about 4.3 g / Mcal, or about 4.35 g / Mcal, or about 4.4 g / Mcal, or about 4.45 g / Mcal, or about 4.5 g / Mcal, or about 4.55 g / Mcal, or about 4.6 g / Mcal, or about 4.65 g / Mcal, or about 4.7 g / Mcal, or about 4.75 g / Mcal, or about 4.8 g / Mcal, or about 4.85 g / Mcal, or about 4.9 g / Mcal, or about 4.95 g / Mcal, or about 5 g / Mcal, or about 5.1 g / Mcal, or about 5.15 g / Mcal, or about 5.2 g / Mcal, or about 5.25 g / Mcal, or about 5.3 g / Mcal, or about 5.35 g / Mcal, or about 5.4 g / Mcal, or about 5.45 g / Mcal, or about 5.5 g / Mcal, or about 5.55 g / Mcal, or about 5.6 g / Mcal, or about 5.65 g / Mcal, or about 5.7 g / Mcal, or about 5.75 g / Mcal, or about 5.8 g / Mcal, or about 5.85 g / Mcal, or about 5.9 g / Mcal, or about 5.95 g / Mcal, or about 6 g / Mcal, or about 6.1 g / Mcal, or about 6.15 g / Mcal, or about 6.2 g / Mcal, or about 6.25 g / Mcal, or about 6.3 g / Mcal, or about 6.35 g / Mcal, or about 6.4 g / Mcal, or about 6.45 g / Mcal, or about 6.5 g / Mcal, or about 6.55 g / Mcal, or about 6.6 g / Mcal, or about 6.65 g / Mcal, or about 6.7 g / Mcal, or about 6.75 g / Mcal, or about 6.8 g / Mcal, or about 6.85 g / Mcal, or about 6.9 g / Mcal, or about 6.95 g / Mcal, or about 7 g / Mcal, or about 7.1 g / Mcal, or about 7.15 g / Mcal, or about 7.2 g / Mcal, or about 7.25 g / Mcal, or about 7.3 g / Mcal, or about 7.35 g / Mcal, or about 7.4 g / Mcal, or about 7.45 g / Mcal, or about 7.5 g / Mcal, or about 7.55 g / Mcal, or about 7.6 g / Mcal, or about 7.65 g / Mcal, or about 7.7 g / Mcal, or about 7.75 g / Mcal, or about 7.8 g / Mcal, or about 7.85 g / Mcal, or about 7.9 g / Mcal, or about 7.95 g / Mcal, or about 8 g / Mcal, or about 8.1 g / Mcal, or about 8.15 g / Mcal, or about 8.2 g / Mcal, or about 8.25 g / Mcal, or about 8.3 g / Mcal, or about 8.35 g / Mcal, or about 8.4 g / Mcal, or about 8.45 g / Mcal, or about 8.5 g / Mcal, or about 8.55 g / Mcal, or about 8.6 g / Mcal, or about 8.65 g / Mcal, or about 8.7 g / Mcal, or about 8.75 g / Mcal, or about 8.8 g / Mcal, or about 8.85 g / Mcal, or about 8.9 g / Mcal, or about 8.95 g / Mcal, or about 9 g / Mcal, or about 9.1 g / Mcal, or about 9.15 g / Mcal, or about 9.2 g / Mcal, or about 9.25 g / Mcal, or about 9.3 g / Mcal, or about 9.35 g / Mcal, or about 9.4 g / Mcal, or about 9.45 g / Mcal, or about 9.5g / Mcal, or about 9.55 g / Mcal, or about 9.6 g / Mcal, or about 9.65 g / Mcal, or about 9.7 g / Mcal, or about 9.75 g / Mcal, or about 9.8 g / Mcal, or about 9.85 g / Mcal, or about 9.9 g / Mcal, or about 9.95 g / Mcal, or about 10 g / Mcal.
[0140] In some embodiments, the food composition as described herein can include from about 0.05 g / Mcal to about 10 g / Mcal of EPA.
[0141] In some embodiments, according to the conversion from g / Mcal to g / Kg (BW) per day described below, the food composition as described herein can include from about 0.0010 to about 1 .0511 g / kg (BW) per day of EPA.
[0142] In some embodiments, the food composition as described herein can include from about 0.05 g / Mcal to about 9 g / Mcal, or from about 0.05 g / Mcal to about 8.5 g / Mcal, or from about 0.05 g / Mcal to about 8 g / Mcal, or from about 0.05 g / Mcal to about 7.5 g / Mcal, or from about 0.05 g / Mcal to about 7 g / Mcal, or from about 0.05 g / Mcal to about 6.5 g / Mcal, or from about 0.05 g / Mcal to about 6 g / Mcal, or from about 0.05 g / Mcal to about 5.5 g / Mcal, or from about 0.05 g / Mcal to about 5 g / Mcal of EPA.
[0143] In some embodiments, the food composition as described herein can include about 0.05 g / Mcal, or about 0.1 g / Mcal, or about 0.15 g / Mcal, or about 0.2 g / Mcal, or about 0.25 g / Mcal, or about 0.3 g / Mcal, or about 0.35 g / Mcal, or about 0.4 g / Mcal, or about 0.45 g / Mcal, or about 0.5 g / Mcal, or about 0.55 g / Mcal, or about 0.6 g / Mcal, or about 0.65 g / Mcal, or about 0.7 g / Mcal, or about 0.75 g / Mcal, or about 0.8 g / Mcal, about 0.9 g / Mcal, about 1 g / Mcal, about 1 .1 g / Mcal, about 1 .2 g / Mcal, about 1 .3 g / Mcal, about 1.4 g / Mcal, about 1.5 g / Mcal, about 1.6 g / Mcal, about 1.7 g / Mcal, about 1 .8 g / Mcal, about 1 .9 g / Mcal, about 2 g / Mcal, about 2.1 g / Mcal, about 2.2 g / Mcal, about 2.3 g / Mcal, about 2.4 g / Mcal, about 2.5 g / Mcal, about 2.6 g / Mcal, about 2.7 g / Mcal, about 2.8 g / Mcal, about 2.9 g / Mcal, about 3 g / Mcal, about 3.5 g / Mcal, about 4 g / Mcal, about 4.5 g / Mcal of EPA.
[0144] In some embodiments, the food composition as described herein can include from about 0.05 g / Mcal to about 5 g / Mcal of EPA.
[0145] In some embodiments, according to the conversion from g / Mcal to g / Kg (BW) per day described below, the food composition as described herein can include from about 0.0010 to about 0.5256 g / kg (BW) per day of EPA.
[0146] In some embodiments, the food composition as described herein can include from about 0.05 g / Mcal to about 19 g / Mcal of DHA.
[0147] In some embodiments, according to the conversion from g / Mcal to g / Kg (BW) per day described below, the food composition as described herein can include from about 0.0010 to about 1 .9971 g / kg (BW) per day of DHA.
[0148] In some embodiments, the food composition as described herein can include from about 0.05 g / Mcal to about 19 g / Mcal, or from about 0.05 g / Mcal to about 18 g / Mcal, or from about 0.05 g / Mcal to about 17 g / Mcal, or from about 0.05 g / Mcal to about 16 g / Mcal, or from about 0.05 g / Mcal to about 15 g / Mcal, or from about 0.05 g / Mcal to about 14 g / Mcal, or from about 0.05 g / Mcal to about 13 g / Mcal, or from about 0.05 g / Mcal to about 12 g / Mcal, or from about 0.05 g / Mcal to about 11 g / Mcal, or from about 0.05 g / Mcal to about 10 g / Mcal; or from about 0.1 g / Mcal to about 19 g / Mcal, or from about 0.1 g / Mcal to about 18 g / Mcal, or from about 0.1 g / Mcal to about 17 g / Mcal, or from about 0.1 g / Mcal to about 16 g / Mcal, or from about 0.1 g / Mcal to about 15 g / Mcal, or from about 0.1 g / Mcal to about 14 g / Mcal, or from about 0.1 g / Mcal to about 13 g / Mcal, or from about 0.1 g / Mcal to about 12 g / Mcal, or from about 0.1 g / Mcal to about 11 g / Mcal, or from about 0.1 g / Mcal to about 10 g / Mcal; or from about 0.15 g / Mcal to about 19 g / Mcal, or from about 0.15 g / Mcal to about 18 g / Mcal, or from about 0.15 g / Mcal to about 17 g / Mcal, or from about 0.15 g / Mcal to about 16 g / Mcal, or from about 0.15 g / Mcal to about 15 g / Mcal, or from about 0.15 g / Mcal to about 14 g / Mcal, or from about 0.15 g / Mcal to about 13 g / Mcal, or from about 0.15 g / Mcal to about 12 g / Mcal, or from about 0.15 g / Mcal to about 11 g / Mcal, or from about 0.15 g / Mcal to about 10 g / Mcal; or from about 0.2 g / Mcal to about 19 g / Mcal, or from about 0.2 g / Mcal to about 18 g / Mcal, or from about 0.2 g / Mcal to about 17 g / Mcal, or from about 0.2 g / Mcal to about 16 g / Mcal, or from about 0.2 g / Mcal to about 15 g / Mcal, or from about 0.2 g / Mcal to about 14 g / Mcal, or from about 0.2 g / Mcal to about 13 g / Mcal, or from about 0.2 g / Mcal to about 12 g / Mcal, or from about 0.2 g / Mcal to about 11 g / Mcal, or from about 0.2 g / Mcal to about 10 g / Mcal of DHA.
[0149] In some embodiments, the food composition as described herein can include about 0.2 g / Mcal, or about 0.3 g / Mcal, or about 0.4 g / Mcal, or about 0.5 g / Mcal, or about 0.6 g / Mcal, or about 0.7 g / Mcal, or about 0.8 g / Mcal, or about 0.9 g / Mcal, or about 1 g / Mcal, or about 1.1 g / Mcal, or about 1.2 g / Mcal, or about 1.3 g / Mcal, or about 1 .4 g / Mcal, or about 1 .5 g / Mcal, or about 1 .6 g / Mcal, or about 1 .7 g / Mcal, or about 1 .8 g / Mcal, or about 1 .9 g / Mcal, or about 2 g / Mcal, or about 3 g / Mcal; or about 4 g / Mcal, or about 5 g / Mcal, or about 6 g / Mcal, or about 7 g / Mcal, or about 8 g / Mcal, or about 9 g / Mcal, or about 10 g / Mcal, or about 11 g / Mcal, or about 12 g / Mcal, or about 13 g / Mcal,or about 14 g / Mcal, or about 15 g / Mcal, or about 16 g / Mcal, or about 17 g / Mcal, or about 18 g / Mcal, or about 19 g / Mcal of DHA.
[0150] In some embodiments, the food composition as described herein can include from about 0.2 g / Mcal to about 10 g / Mcal of DHA.
[0151] In some embodiments, according to the conversion from g / Mcal to g / Kg (BW) per day described below, the food composition as described herein can include from about 0.0040 to about 1 .0511 g / kg (BW) per day of DHA.
[0152] In some embodiments, a source of EPA and DHA can be selected from, without limitation, fish oil, fish meal, algae oil, eggs, oyster, chia seed, walnuts, soybeans, Green Leaped Mussel or a mixture thereof.
[0153] The food composition, for instance the nutritionally complete and balanced feline food composition, as described herein can include curcuminoids.
[0154] In some embodiments, the food composition as described herein can include from about 1.6 mg / Mcal to about 4400 mg / Mcal of curcuminoids.
[0155] In some embodiments, according to the conversion from mg / Mcal to mg / Kg (BW) per day described below, the food composition as described herein can include from about 0.0321 to about 462.4930 mg / kg (BW) per day of curcuminoids.
[0156] In some embodiments, the food composition as described herein can include from about 1.6 mg / Mcal to about 4400 mg / Mcal, or from about 1.7 mg / Mcal to about 4300 mg / Mcal, or from about 2 mg / Mcal to about 4000 mg / Mcal, or from about 5 mg / Mcal to about 3500 mg / Mcal, or from about 10 mg / Mcal to about 3200 mg / Mcal, or from about 20 mg / Mcal to about 3000 mg / Mcal, or from about 25 mg / Mcal to about 2800 mg / Mcal, or from about 30 mg / Mcal to about 2500 mg / Mcal, or from about 35 mg / Mcal to about 2200 mg / Mcal, or from about 40 mg / Mcal to about 2000 mg / Mcal, or from about 45 mg / Mcal to about 1800 mg / Mcal, or from about 50 mg / Mcal to about 1500 mg / Mcal, or from about 50 mg / Mcal to about 1000 mg / Mcal, or from about 55 mg / Mcal to about 800 mg / Mcal, or from about 55 mg / Mcal to about 500 mg / Mcal, or from about 55 mg / Mcal to about 300 mg / Mcal, or from about 60 mg / Mcal to about 200 mg / Mcal of curcuminoids.
[0157] In some embodiments, the food composition as described herein can include about 30 mg / Mcal, or about 35 g / Mcal, or about 40 g / Mcal, or about 45 g / Mcal, or about 50 g / Mcal, or about 55 g / Mcal, or about 60 mg / Mcal, or about 65 mg / Mcal or about 70 mg / Mcal, or about 75 mg / Mcal , or about 80 mg / Mcal, or about 81 mg / Mcal, or about 82 mg / Mcal, or about 83 mg / Mcal, or about 84 mg / Mcal, or about 85 mg / Mcal,or about 90 mg / Mcal, or about 95 mg / Mcal, or about 100 mg / Mcal, or about 150 g / Mcal, or about 200 g / Mcal, or about 250 g / Mcal, or about 300 g / Mcal, or about 350 g / Mcal, or about 400 g / Mcal, or about 450 g / Mcal, or about 500 g / Mcal of curcuminoids.
[0158] In some embodiments, curcuminoids can include curcumin or a derivative of curcumin.
[0159] In some embodiments, curcuminoids can include curcumin, demethoxycurcumin, bisdemethoxycurcumin and / or tetrahydrocurcumin.
[0160] In some embodiments, the curcuminoid included within the food composition as described herein can be of any format, including a powder or lipid extract.
[0161] In some embodiments, a source of curcuminoid can be, without limitation, a root of turmeric.
[0162] In some embodiments, curcuminoid can be mixed with phospholipids and / or cellulose, starch or derivatives thereof to form complexes. This may assist in stability and / or to further increase solubility and bioavailability of the curcuminoid.
[0163] As non-limitative example, the curcuminoid can be mixed with, without limitation, essential oils, piperine or bromelain. The curcuminoid can also be mixed with phosphatidycholine, for example lecithin.
[0164] In some embodiments, curcuminoids can be curcumin, which is the most active curcuminoid. In some embodiments, curcumin according to the present disclosure can encompass demethoxycurcumin, bisdemethoxycurcumin and / or tetrahydrocurcumin.
[0165] The food composition, for instance the nutritionally complete and balanced feline food composition, as described herein can include hydrolyzed collagen.
[0166] In some embodiments, the food composition as described herein can include from about 0.07 g / Mcal to about 215 g / Mcal of hydrolyzed collagen.
[0167] In some embodiments, according to the conversion from g / Mcal to g / Kg (BW) per day described below, the food composition as described herein can include from about 0.0014 to about 22.5991 g / kg (BW) per day of hydrolyzed collagen.
[0168] In some embodiments, the food composition as described herein can include from about 0.07 g / Mcal to about 215 g / Mcal, or from about 0.1 g / Mcal to about 200 g / Mcal, or from about 0.5 g / Mcal to about 150 g / Mcal, or from about 1 g / Mcal to about 100 g / Mcal, or from about 2 g / Mcal to about 50 g / Mcal, or from about 3 g / Mcal to about 25 g / Mcal, or from about 3.5 g / Mcal to about 20 g / Mcal, or from about 3.8 g / Mcalto about 15 g / Mcal, or from about 4 g / Mcal to about 10 g / Mcal, or from about 4 g / Mcal to about 5 g / Mcal of hydrolyzed collagen.
[0169] In some embodiments, the food composition as described herein can include from about 4 g / Mcal, or about 4.1 g / Mcal, or about 4.2 g / Mcal, or about 4.3 g / Mcal, or about 4.4 g / Mcal, or about 4.5 g / Mcal, or about 4.6 g / Mcal, or about 4.7 g / Mcal, or about 4.8 g / Mcal, or about 4.9 g / Mcal, or about 5 g / Mcal of hydrolyzed collagen.
[0170] In some embodiments, hydrolyzed collagen can include a combination of at least glycine, proline and hydroxyproline.
[0171] In some embodiments, hydrolyzed collagen can include about 25% by weight of proline and / or hydroxyproline, about 20% by weight of glycine, about 11% by weight of glutamic acid, about 8% by weight of arginine, about 8% of alanine, about 16% by weight of other essential amino acids and about 12% by weight of other non- essential amino acids.
[0172] A hydrolyzed collagen can be obtained by the enzymatic hydrolysis of collagenous tissues found in the bones, skin, and connective tissue of animals such as cattle, fish, horses, pigs, reptiles, and rabbits. Hydrolyzed collagen is well digested and can be accumulated in cartilage.
[0173] In some embodiments, the food composition as described herein can include other nutrients and / or ingredients.
[0174] In some embodiments, the food composition as described herein can further include, but is not limited to, proteins, carbohydrates, fibers, fats, vitamins and / or minerals.
[0175] Notably, in such embodiments, these proteins, carbohydrates, fibers, fats, vitamins and / or minerals are supplementary or in complement to the EPA and DHA content, and optionally the curcuminoids and the combination of glycine, proline and hydroxyproline contents, incorporated into the food composition as described herein.
[0176] Accordingly, the amount of the other nutrients and / or ingredients shall be present in an adequate amount to ensure maintenance of lean body mass of the companion animal, particularly the dog or the cat, while no being toxic for the companion animal, particularly the dog or the cat.
[0177] In some embodiments, the food composition as described herein can include proteins.
[0178] Accordingly, the protein level shall be high enough to ensure maintenance of lean body mass of the companion animal, particularly the canine or the feline while no being toxic for the companion animal, particularly the canine or the feline.
[0179] In some embodiments, a food composition as described herein can include from about 40 g / Mcal to about 140 g / Mcal of protein.
[0180] In some embodiments, a food composition as described herein can include from about 40 g / Mcal, about 45 g / Mcal, about 50 g / Mcal, about 55 g / Mcal, about 60 g / Mcal, about 65 g / Mcal, about 70 g / Mcal, about 75 g / Mcal, about 80 g / Mcal, about 85 g / Mcal, about 90 g / Mcal, about 95 g / Mcal, about 100 g / Mcal, about 105 g / Mcal, about 110 g / Mcal, about 115 g / Mcal, about 120 g / Mcal, about 125 g / Mcal, about 130 g / Mcal, about 135 g / Mcal, about 136 g / Mcal, about 137 g / Mcal, about 138 g / Mcal, about 139 g / Mcal or about 140 g / Mcal. of protein.
[0181] In some embodiments, a food composition as described herein can include from about 45 g / Mcal to about 130 g / Mcal of protein.
[0182] In some embodiments, a food composition as described herein can include from about 48 g / Mcal to about 110 g / Mcal of protein.
[0183] In some embodiments, a food composition as described herein that can be adapted to a food aimed at reducing excessive body weight can include from about 90 g / Mcal to about 140 g / Mcal of protein.
[0184] In some embodiments, a food composition as described herein that can be adapted to a food aimed at supporting renal functions can include from about 40 g / Mcal to about 100 g / Mcal of protein.
[0185] In some embodiments, a food composition as described herein that can be adapted to a food aimed at supporting joint functions can include from about 60 g / Mcal to about 140 g / Mcal of protein.
[0186] In some embodiments, a food composition as described herein that can be adapted to a hypoallergenic food can include from about 50 g / Mcal to about 125 g / Mcal of protein.
[0187] In some embodiments, a food composition as described herein that can be adapted to a food aimed at reducing Gastrointestinal (Gl) disorders can include from about 55 g / Mcal to about 110 g / Mcal of protein.
[0188] In some embodiments, a food composition as described herein can include a plurality of source of proteins. In some embodiments, the protein can be nonhydrolyzed protein. In some embodiments, the protein can be hydrolyzed protein. Aningredient that can be a protein source for the manufacture of a food composition as described herein can originate from an animal protein source and / or a vegetal protein source. Notably, an animal protein source and / or a vegetal protein source can be a raw material.
[0189] In some embodiments, a protein source can be a mixture of one or more animal protein source or one or more vegetable protein source, or one or more animal and vegetal protein sources. A source of protein in a raw material can also provide to the food composition as described herein a source of water, a source of fat, a source of ash, a source of fibers, and / or a source of vitamins. The nutritional composition of the source of protein depending on the quality and the specificity of the raw material. For instance, an animal source of protein can also provide fats.
[0190] An animal protein source can be selected from, but is not limited to, poultry, poultry meal, poultry by-product, lamb, lamb meals, pork, pork by-product, beef, beef by-products, white fish, milk proteins, egg, venison or a combination thereof.
[0191] Poultry can encompass chicken, duck, turkey, geese, and quail.
[0192] A vegetable protein source can be selected, without limitation, from soybean meal, soy protein isolate, rice, soy protein concentrate, maize gluten, wheat gluten, gluten, tofu, green lentils, carrot, potato, beets, corn gluten meal, corn protein concentrate or a combination thereof.
[0193] Protein content of a food composition can be determined by any methods known by the person of skill in the art.
[0194] In some embodiments, the food composition as described herein can include fats.
[0195] In some embodiments, the food composition can include fats from an animal fat source and / or a vegetable fat source. A vegetable fat source can include, without limitation, wheat, soy, sunflower, safflower, rapeseed, olive, borage, flaxseed, peanuts, blackcurrant seed, cottonseed, wheat, germ, corn germ as well as oils derived from these and combinations thereof. An animal fat source can include, without limitation, chicken crude fat, turkey crude fat, beef crude fat, duck crude fat, pork crude fat, lamb crude fat, fish oil or any meat, meat by-products, seafood, fish by-products, dairy, eggs or a combination thereof.
[0196] Fats can be supplied by any sources known by the person skilled in the art.
[0197] In some embodiments, a food composition as described herein can include from about 10 g / Mcal to about 80 g / Mcal of fat.
[0198] In some embodiments, a food composition as described herein can include about 10 g / Mcal, or about 15 g / Mcal, or about 20 g / Mcal, or about 25 g / Mcal, or about 30 g / Mcal, or about 35 g / Mcal, or about 40 g / Mcal, or about 45 g / Mcal, or about 50 g / Mcal, or about 55 g / Mcal, or about 60 g / Mcal, or about 65 g / Mcal, or about 70 g / Mcal, or about 75 g / Mcal or about 80 g / Mcal of fat.
[0199] In some embodiments, a food composition as described herein can include from about 22 g / Mcal to about 75 g / Mcal, of fat.
[0200] In some embodiments, a food composition as described herein that can be adapted to a food aimed at reducing excessive body weight can include from about 10 g / Mcal to about 50 g / Mcal of fat.
[0201] In some embodiments, a food composition as described herein that can be adapted to a food aimed at supporting renal functions can include from about 10 g / Mcal to about 80 g / Mcal of fat.
[0202] In some embodiments, a food composition as described herein that can be adapted to a food aimed at supporting joint functions can include from about 15g / Meal to about 45 g / Mcal of fat.
[0203] In some embodiments, a food composition as described herein that can be adapted to a hypoallergenic food can include from about 15 g / Mcal to about 70 g / Mcal of fat.
[0204] In some embodiments, a food composition as described herein that can be adapted to a food aimed at reducing Gastrointestinal (Gl) disorders can include from about 15 g / Mcal to about 70 g / Mcal of fat.
[0205] The total amount of fat in the food compositions as described herein includes the amount of EPA and DHA.
[0206] Fat content of a food composition as described herein can be determined by any methods known by the person of skill in the art.
[0207] In some embodiments, the food composition as described herein can include fibers. As used herein fibers designates soluble fibers and insoluble fibers.
[0208] In some embodiments, the food composition as described herein can include from about 5 g / Mcal to about 90 g / Mcal of fiber.
[0209] In some embodiments, the food composition as described herein can include about 5 g / Mcal, about 6 g / Mcal, about 7 g / Mcal, about 8 g / Mcal, about 9 g / Mcal,about 10 g / Mcal, about 15 g / Mcal, about 20 g / Mcal, about 25 g / Mcal, about 30 g / Mcal, about 35 g / Mcal, about 40 g / Mcal, about 45 g / Mcal, about 50 g / Mcal, about 55 g / Mcal, about 60 g / Mcal, about 65 g / Mcal, about 70 g / Mcal, about 75 g / Mcal, about 80 g / Mcal, about 85 g / Mcal, about 90 g / Mcal of fiber.
[0210] Illustratively, a food composition as described herein can include from about 10 g / Mcal to about 85 g / Mcal of fiber.
[0211] In an embodiment, a food composition as described herein that can be adapted to a food aimed at reducing excessive body weight can include from about 10 g / Mcal to about 90 g / Mcal of fiber.
[0212] In an embodiment, a food composition as described herein that can be adapted to a food aimed at supporting renal functions can include from about 5 g / Mcal to about 55 g / Mcal of fiber.
[0213] In an embodiment, a food composition as described herein that can be adapted to a food aimed at supporting joint functions can include from about 20 g / Mcal to about 65 g / Mcal of fiber.
[0214] In an embodiment, a food composition as described herein that can be adapted to a hypoallergenic food can include from about 10 g / Mcal to about 45 g / Mcal of fiber.
[0215] In an embodiment, a food composition as described herein that can be adapted to a food aimed at reducing Gastrointestinal (Gl) disorders can include from about 10 g / Mcal to about 70 g / Mcal of fiber.
[0216] In some embodiments, a source of fibers can be selected from, but is not limited to, beet pulp, guar gum, chicory root, psyllium, pectin, blueberry, cranberry, squash, apples, oats, beans, citrus, barley, or peas cellulose, whole wheat products, wheat oat, corn bran, flax seed, grapes, celery, green beans, cauliflower, potato skins, fruit skins, vegetable skins, peanut hulls, soy fiber and a combination thereof.
[0217] Fiber’s content of a food composition as described herein can be determined by any methods known by the person of skill in the art.
[0218] In some embodiments, the food composition as described can also include preservatives, trace elements and / or coloring.
[0219] In some embodiments, a food composition as described herein can further include a diluent and / or an excipient.
[0220] A diluent can encompass water or broth or stock. Broth can generally be made by simmering meat, such as chicken, beef or fish, or vegetables in water. Stockcan generally be made by simmering bones in water, and eventually with vegetables and / or meat.
[0221] An excipient can encompass antioxidants, flavors, prebiotics, probiotics or taurine.
[0222] In some embodiments, a food composition as described herein does not include polyphenols.
[0223] Typically, a food composition as disclosed herein can include EPA and DHA and, optionally, one or more further ingredient, a source of protein, a source of ash, a source of fibers, a source of fat, additives and / or vitamins. The sum of the weight of each of the ingredients comprised therein amounting, on a dry matter basis, to 100% by weight.
[0224] Typically, a food composition as disclosed herein can include several substances and / or nutriments such as protein, ash, fibers, fat, additives and / or vitamins. The sum of the weight of each of the substances and / or nutriments comprised therein amounting, on a dry matter basis, to 100% by weight.
[0225] In some embodiments, a food composition as described herein can consist of a wet food composition, a dry food composition or a semi-moist food composition.
[0226] In some embodiments, a food composition as described herein can consist of functional complement.
[0227] A dry food composition can refer to a food composition having a moisture content of less than about 12% by weight, relative to the total weight of the food composition.
[0228] A process for determining the moisture content of a food composition can include at least the steps of (i) selecting a representative sample of the food composition, (ii) weighing the sample, (iii) then subjecting the sample to complete dehydration in a temperature-controlled oven, typically around 100°C, until all water is evaporated, (iv) after cooling in a desiccator, weighing again the dehydrated sample. The moisture content is then calculated using the formula: Moisture Content (%) = [(Initial Mass - Mass after dehydration) I Initial Mass] x 100.
[0229] In some embodiments, a dry food composition as described herein can have a moisture content ranging from about 4% to about 12% by weight, relative to the total weight of the food composition.
[0230] In some embodiments, a dry food composition as described herein can have a moisture content of about 4%, or about 5%, or about 6%, or about 7%, or about 8%, or about 9%, or about 10%, or about 11%, or about 12% by weight, relative to the total weight of the food composition.
[0231] Typically, a dry food composition can have a moisture content of about 8% by weight, relative to the total weight of the food composition.
[0232] In some embodiments, a dry food composition can be formed by an extrusion process.
[0233] In some embodiments, a dry food composition can be formed from a core and a coating to form a dry food composition that is coated, also called a coated dry animal food composition.
[0234] In some embodiments, a dry food composition can be a kibble.
[0235] A semi-moist food composition refers to a food composition having a moisture content ranging from about 13% to about 49 % by weight, relative to the total weight of the food composition.
[0236] Typically, a semi-moist food composition is the final product of a process allowing a moisture content value that is intermediate between a dry food and a wet food. In some embodiments, the said process can comprise a step of adding a humectant agent. In some embodiments, the said process can comprise an extrusion step and a subsequent treatment step with Super-Heated Stream (SHS). As non- limitative example, semi-moist food can be obtained using Super-Heated Stream (SHS) processes such as processes or methods described in the published patent applications W02009 / 018990, W02009 / 018996, WO2010 / 112097, WO201 4 / 122072,WO201 6 / 071372 and / or WO2016 / 071367, the disclosures of which are incorporated herein in their entireties.
[0237] In some embodiments, a semi-moist food composition as described herein can have a moisture content of about 13%, or about 14%, or about 15%, or about 16%, or about 17% or about 18, or about 9%, or about 20% or about 21%, or about 22%, or about 23%, or about 24%, or about 25%, or about 26%, or about 27%, or about 28%, or about 29%, or about 30%, or about 31%, or about 32%, or about 33%, or about 34%, or about 35%, or about 36%, or about 37%, or about 38%, or about 39%, or about 40%, or about 41%, or about 42%, or about 43%, or about 44%, or about 45%, or about 46%, or about 47%, or about 48%, or about 49% by weight, relative to the total weight of the food composition.
[0238] Typically, a semi-moist food composition can have a moisture content of about 20% by weight, relative to the total weight of the food composition.
[0239] A wet food composition refers to a food composition having a moisture content of more than about 50% by weight, relative to the total weight of the food composition.
[0240] In some embodiments, a wet food composition refers to a food composition having a moisture content ranging from about 50% to about 90% by weight, relative to the total weight of the food composition.
[0241] In some embodiments, a wet food composition as described herein can have a moisture content of about 50%, or about 55%, or about 60%, or about 65%, or about 70%, or about 75%, or about 80%, or about 85%, or about 90% by weight, relative to the total weight of the food composition.
[0242] Typically, a wet food composition can have a moisture content of about 80% by weight, relative to the total weight of the food composition.
[0243] In general, a wet food composition is the final product of a process including a final step of sterilization (instead of a drying step).
[0244] In some embodiments, a wet food composition can consist of a chunk form, more particularly of chunks in gravy form.
[0245] In some embodiments, a wet food composition can consist of chunks and gravy, chunks in jelly, loaf, mousse, terrine or bites form.
[0246] In some particular embodiments, a food composition as described herein can consist of a dry food composition.
[0247] In some embodiments, a functional complement can consist of chews, soft chews, tablets, powders, liquids, beads, gums, or any other similar format known by the person skilled in the art.
[0248] The food composition as disclosed herein is nutritionally complete and balanced; and palatable for a companion animal, particularly a canine or a feline.
[0249] The food composition as disclosed herein is a functional complement, and palatable for a companion animal, particularly for a canine or a feline.
[0250] In some embodiments, a feline can encompass a cheetah, a puma, a jaguar, a leopard, a lion, a lynx, a liger, a tiger, a panther, a bobcat, an ocelot, a smilodon, a caracal, a serval and / or a cat.
[0251] In some embodiments, a feline can be a cat, in particular a domestic cat.
[0252] In some embodiments, a companion animal, particularly a canine or a feline, may exhibit signs of allodynia, signs of hyperalgesia and / or signs of central sensitization.Uses and methods
[0253] An object of the present disclosure relates to a food composition as described herein for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof.
[0254] An object of the present disclosure relates to a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof comprising at least a step of providing a nutritionally complete and balanced food composition as described herein to the companion animal, specifically a canine or a feline.
[0255] An object of the present disclosure relates to the use of a food composition as described herein in the manufacture of a medicament for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof.
[0256] In particular, the method comprises administering to said companion animal, specifically a canine or a feline a food composition which comprises EPA and DHA, and optionally curcuminoids and / or hydrolyzed collagen as described herein.
[0257] In some embodiments, the chronic inflammatory joint disease can be selected from, without limitation, osteoarthritis, bursitis, rheumatoid arthritis, juvenile rheumatoid arthritis, infectious arthritis, psoriasis-related arthritis or reactive arthritis disease.
[0258] In some particular embodiments, the chronic inflammatory joint disease can consist of osteoarthritis.
[0259] Osteoarthritis (OA) is a degenerative and inflammatory condition that affects the joints in mammals. It is also known as degenerative arthritis or degenerative joint disease. Osteoarthritis is a group of abnormalities involving degradation of joints, including articular cartilage and sub-chondral bone. Osteoarthritis is the consequenceof an imbalance of catabolism and anabolism, wherein catabolism is increased; anabolism is decreased causing the inflammation of chondrocytes. Chondrocytes are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. The food composition as described herein has demonstrated to provide, inter alia, a decrease in inflammation by the resolution of the inflammation, a decrease in pain of the companion animal, particularly a canine or a feline, and an increase of the mobility of the companion animal. Thus, the food composition as described herein can prevent and / or treat osteoarthritis in companion animals, such as canines or felines.
[0260] In some embodiments, the treatment and / or the prevention of a chronic inflammatory joint disease with the food composition as described herein can also encompass the amelioration of the life condition of the companion animal, particularly the canine or the feline, that is fed.
[0261] More particularly, the treatment and / or the prevention of a chronic inflammatory joint disease with the food composition as described can encompass the reduction and / or the alleviation of the pain; the reduction and / or the alleviation of allodynia; the reduction and / or the alleviation of hyperalgesia ; and / or the reduction and / or the alleviation of central sensitization of the companion animal, particularly the canine or the feline, that is fed.
[0262] Additionally, the treatment and / or the prevention of a chronic inflammatory joint disease with the described food composition implies the resolution of the inflammation. Hence, in some embodiments, the food composition described herein can be used in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, by involving the resolution of the inflammation. Such resolution can be distinguished by the activation of Specialized Pro-Resolving Mediators (SPMs) such as, without limitations, 18-HEPE, 15-HEPE, 17-HDOHE, RVD3, RVD5, 14-HDOHE, DHEA, Maresins 1 , and / or Maresin 2.
[0263] In some embodiments, a food composition as described herein for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof, can be formulated to be administered to the companion animal daily as part of its diet.
[0264] In the field of pet nutrition, it is well-established that those skilled in the art possess the knowledge and expertise to adapt the formulation of a food composition to align with specific feeding recommendations for the target animal. For instance, if the recommendation specifies that a companion animal should be fed once a day, twice a day, and / or only on specific days of the week, the skilled person can readily modify the food composition accordingly.
[0265] In some embodiments, a food composition as described herein for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof, can be formulated to be provided to the companion animal in need thereof in alternation with another food composition. In some embodiments, the said another food composition can be another nutritionally complete and balanced food composition or a functional complement. In particular, another food composition can be selected from food compositions in the art, including the large variety of commercialized food compositions adapted to canines or felines.
[0266] In some embodiments, a food composition as described herein for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof, can be formulated to be provided to the companion animal in need thereof every other day, with said another food composition being provided on alternate days.
[0267] In some embodiments, a food composition as described herein for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof, can be formulated to be provided to the companion animal in need thereof from several weeks to several years, depending notably on the severity of the joint disease.
[0268] In some embodiments, a food composition as described herein for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof, can be formulated to be suitable to be provided to the companion animal in need thereof once a day or twice a day.
[0269] In some embodiments, a food composition as described herein for use in a method for treating and / or preventing a chronic inflammatory joint disease in acompanion animal, particularly a canine or a feline, in need thereof, can be formulated to be suitable to be provided to the companion animal in need thereof every day in a week over a period of 1 month or more, or 2 months or more, or 3 months or more, or 4 months or more, or 5 months or more.
[0270] In some embodiments, a food composition as described herein for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof, can be formulated to be provided to a companion animal in need thereof during a longer period of time, such as during 6 months or more, or 12 months or more, either (i) according to a feeding schedule wherein the companion animal exclusively fed the food composition as described herein or (ii) according to a feeding schedule wherein the companion animal alternating the food composition described herein and another corresponding food composition.
[0271] A food composition as described herein for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof, can be formulated in such a manner that the body weight of the companion animal is not significantly affected.
[0272] In some embodiments, a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal, particularly a canine or a feline, in need thereof can further include a step of making a feeding recommendation that includes a food composition as described herein.
[0273] An object of the present disclosure relates to a method for feeding a companion animal, particularly a canine or a feline, wherein the method includes at least a step of administering a food composition according to the present disclosure to the companion animal. In some particular embodiments, the companion animal has a chronic inflammatory joint disease.
[0274] The present disclosure also relates to a method of manufacturing a food composition for a companion animal, particularly a canine or a feline, as described herein including at least a step of mixing all the ingredients together.
[0275] The food composition as described herein can be prepared according to the techniques which are well known to a person skilled in the art.
[0276] The food composition can be made according to any method known in the art such as in Waltham Book of Dog and Cat Nutrition, Ed. ATB Edney, Chapter by A. Rainbird, entitled "A Balanced Diet" in pages 57 to 74 Pergamon Press Oxford. For instance, a process for the manufacture of a food composition as described herein can include mixing together ingredients having a source of EPA and DHA, optionally a source of curcuminoids and / or a source of hydrolysed collagen and forming a food composition. Heating and cooking can be applied to any one or more of the ingredients prior to, during or following the mixing.
[0277] This disclosure can be further illustrated by the following examples of embodiments thereof, although it will be understood that these examples are included merely for purposes of illustration and are not intended to limit the scope of the disclosure.EXAMPLESIndexBW : Body weightDHA: Docosahexaenoic acidDHEA: Docosahexaenoyl ethanolamideEPA: Eicosapentaenoic acidEPEA: Eicosapentaenoyl ethanolamideOA : OsteoarthritisPGA: Podobarometric gait analysisPVF: Peak vertical forcePWT : Paw withdrawal thresholdMar-1 : Maresin 1Mar- 2: Maresin 2Montreal Instrument for Cat Arthritis Testing, for Veterinarians (MI-CAT(V))NAM: Night-time actimetry monitoringRMTS: Response to mechanical temporal summationRvE1 : E Resolvin 1RvE2: E Resolvin 2RvD5: Resolvin D5SAC: Stairs assay complianceSPMs: Specialized Pro-Resolving MediatorsVI: vertical impulseW: week eCBS: endocannabinoidsEXAMPLE 1 : Evaluation of the efficacy of the food composition on functional parameters and lipids metabolites in cats suffering from osteoarthritisA. MATERIAL AND METHODS
[0278] The goal of the study is to evaluate the pain relieving / functional impact of a nutritionally complete and balanced dry food composition including a higher amountof DHA than EPA (composition A) and its impact on specialized pro-resolving mediators (SPMs) and endocannabinoids.
[0279] This study was a randomized, blinded, placebo- and time-controlled study and comply with the Canadian Council on Animal Care (CCAC) guidelines on laboratory animal facilities - characteristics, design, and development (2003). It has been performed on cats suffering from osteoarthritis.
[0280] The composition A was compared to a control dry food composition (composition B), excluding EPA and DHA (placebo diet).
[0281] Both Cohort 1 and Cohort 2 include adult cats, all having radiographic and functional (painful) evidence of hind limb osteoarthritis (OA) previously assessed by radiographs.
[0282] The study was divided into three phases:1) acclimation phase (Week -5 to Baseline): all cats (29) received composition B;2) treatment phase (Baseline to Week 12): After randomization, Cohort 1 received composition A and Cohort 2 received composition B;3) recovery phase (Week 13 to Week 16): Cohort 1 and Cohort 2 received composition B.
[0283] Cats were fed twice daily with the food compositions, formulated to meet the nutritional levels established by the AAFCO (Association of American Feed Control Officials). Both the food compositions A and B were isocaloric (about 3700-3800 Kcal / kg) and palatable.
[0284] Table 1 : Key nutritional ingredients of compositions A and BProtein total can include glycine, proline and hydroxyproline. The composition A contains 1 ,6% as fed (4,28 g / Mcal) of hydrolyzed collagen.Other ingredients; Composition A: crude fiber 5.8% (15.52 g / Mcal), moisture 5.9%, ash 5.4% (14.45 g / Mcal), curcuminoids 0.031% (0.083 g / Mcal), other 40.97% (109.60 g / Mcal). Composition B: crude fiber 5.2% (13.75 g / Mcal), moisture 5.5%, ash 5.4% (14.28 g / Mcal), curcuminoids 0%, other 42.5% (112.4 g / Mcal)B. PARAMETERS EVALUATED DURING THE STUDY
[0285] A complete set of pain / functional evaluation methods have been performed.1. Primary functional evaluation outcome were:• Cat mobility
[0286] Night-time actimetry monitoring (NAM) activity recorded by Telemetered locomotor activity recording measuring continuously cat mobility. NAM recordings considered for the analyses was captures between 5:00 PM to 6:58 AM during weekend. This choice of timing sequence was supported by previous studies and the fact that NAM was reported as more specific, sensitive and responsive to analgesic in osteoarthritic cats (as compared to daylight-time actimetry monitoring). (Guillot et al. Epub 2013; Guillot et al. PLoS One. 2014; Monteiro Epub 2016; Monteiro et al. PLoS One. 2017; KI i nek et al. J Feline Med Surg 2018).
[0287] The intensity of activity was collected over the three 14-hours night-time periods in each weekend and summated to give the NAM recording over each weekend. The first three weekends were discarded.• Clinical Metrology Instrument (CMI)
[0288] To evaluate the pain in osteoarthritic cats, it was used a highly refined pain assessment method, the Montreal Instrument for Cat Arthritis Testing for Veterinarians (Klinck et al. 2015; Klinck et al. J Feline Med Surg 2018). Test was performed at BSL, week (W) 4, W8, W12 and W16.2. Secondary functional evaluation outcome were :• Podobarometric gait analysis (PGA)
[0289] PGA uses a pressure-sensitive walkway mattress and measuring peak vertical force (PVF) (Strideway HRSW2® System, Tekscan Inc, Boston, MA, USA). Testwas performed at BSL, W4, W8, W12 and W16 (Moreau et al. Res Vet Sci. 2013; Moreau et al. Can Vet J. 2014).• Cat fatigue
[0290] Stairs assay compliance (SAC) measuring cat fatigue (Delsart 2022). Test was performed at BSL, W4, , W12 and W16.• Allodynic cats
[0291] In order to determine is cat is allodynic or non-allodynic, it is evaluated the Paw withdrawal threshold (PWT) using electronic von Frey esthesiometer measuring tactile allodynia (hypersensitivity). Test was performed at BSL, W4, W8, W12 and W16.
[0292] The allodynia threshold is defined at the lower quartile level. This threshold is defined for hind limbs and for fore limbs. To be considered as allodynic, a cat needs to have at least two values under the allodynia threshold corresponding to the limb category, hind or fore limbs.3. Blood samples were collected from the cats to perform:• Dosage of the plasmatic level of Specialized Pro-Resolving Mediators (SPMs) and endocannabinoids.
[0293] Tests were performed at BSL, W8, W12 and W16. Samples were extracted using oasis HLB 96 wells solid phase extraction (Waters). LC-MS / MS analysis were performed on UHPLC system (Agilent LC1290 Infinity) coupled to Agilent 6490 triple quadrupole MS (Agilent Technologies) equipped with electro-spray ionization operating in negative mode.
[0294] The following molecules were quantified:- 17-HDoHE, RvD5 and Protectin PDX,- 14-HDoHE, Mar-1 and Mar-2,- 18 HEPE, RvE1 and RvE2,- Lipoxins (LXA4 and LXB4),- eCBS: Endocannabinoids.C. RESULTS OF PAIN / MOBILITY ASSESSMENT
[0295] Both test and control groups were equally represented for gender, body weight (BW), radiographic scoring, as well as initial MI-CAT(V) and RMTS values. Allpresented diet (compositions A and B) was well-accepted. No cat presented any significant gastro-intestinal disturbances. The statistical analysis of body weight did not reveal any Cohort effect (P=0.292). a. Cat mobility
[0296] Cohort 1 , n=15, Cohort 2, n=13 except at week 16, n=12. The evolution of the NAM is represented in the Figure 1 (% of change vs BSL mean). Linear regression shows increasing mobility for Cohort 1 and decreasing mobility for Cohort 2 overtime, with an inflexion point between both linear regressions around W6.
[0297] The distribution of individuals as responders (showing an ascending or null slope of evolution in NAM) and non-responders (displaying a descending slope) confirms the significant treatment effect observed in Cohort 1 (which received composition A during the treatment phase). In this cohort 1 , a majority of OA cats (66.7% of responder - 33.3% of non-responder) showed improvement in their condition. Conversely, in Cohort 2 (which received composition B during the treatment phase), a majority of cats experienced deterioration in their mobility over the same period (76.9% of non-responder - 23.1% of responder). b. Clinical Metrology Instrument (CMI)
[0298] Cohort 1 , n=15 and Cohort 2, n=14 except for week 16, n=13.
[0299] Test results are represented in Figure 2. It is shown a significant decrease in osteoarthritis (OA) associated biomechanical alteration for cats in Cohort 1 (which received composition A during the treatment phase) whereas it is observed an increase OA associated biomechanical alteration overtime for cats in Cohort 2 (which received composition B during the treatment phase). Specifically, at week 8 and subsequent weeks, significantly less biomechanical alteration is observed in cats of cohort 1 compared to cats in cohort 2. c. Podobarometric gait analysis (PGA)
[0300] Cohort 1 , n=15, Cohort 2, n= 13 except for week 16, n=12. Test results are represented in Figure 3.
[0301] Graph shows an increasing tendency of most affected hind limb PVF (Peak Vertical Force) values for cats in Cohort 1 (which received the composition A during the treatment phase), suggesting lameness improvement. For cats in Cohort 2(which received the composition B during the treatment phase), graph shows decreasing of most affected hind limb PVF values, indicating lameness deterioration. d. Stair assay compliance
[0302] Cohort 1 , n=15, Cohort 2, n=14 except for week 16, n=13. Test results are represented in Figures 4 and 5.
[0303] Graph in figure 4 shows increasing numbers of Cohort 1 cats improving stairs overtime, while cats in Cohort 2 remained stable. With a significant improvement in cohort 1 cats versus cohort 2 cats at week 16.
[0304] Histogram in figure 5 shows a decrease in averaged time required to complete one passage up the 16 stairs for Cohort 1 cats overtime, while Cohort 2 cats remained stable. e. Allodvnic cats
[0305] Cohort 1 , n=15, Cohort 2, n=14 except for week 16, n=13.
[0306] The evaluation of PWT permits to determine if a cat is allodynic or non- allodynic as described in Guillot et. al (Vet J. 2013 Jun;196(3):360-7). In cohort 1 , 7 / 15 cats were classified as allodynic, and in cohort 2, 9 / 14 cats were classified as allodynic at baseline. 57% of the allodynic cats were classified as responders for the parameter actimetry in cohort 1 (which received the composition A during the treatment phase) while only 22% of the allodynic cats were classified as responders inside the cohort 2 (which received the composition B during the treatment phase). f. Number of responders for each assays
[0307] The treatment responder rate was calculated for each following outcome at four timepoints (week 04, 08, 12 and 16): Peak Vertical Force (PVF, normalized by stance time duration; responder = increase in PVF vs. BSL (Baseline)), Stairs Assay Compliance (SAC, number of stairs up & down; responder = increase in number vs. BSL), and Montreal Instrument for Cat Arthritis Testing, for Veterinarians (MI-CAT(V), 1 to 3 observers at each timepoint; responder = decrease in MI-CAT(V) over 15% vs. BSL) (Delsart et al. Animals (Basel). 2024). Night-time Actimetry Monitoring (NAM; overall assessment) was continuous (measure epoch of 2 min) over 20 weekends (three as baseline, and 17 after initiating both diets administration over 13 successive weeks and four weeks of recovery); responder = positive or null slope after linearrepresentation. The treatment responder rates were compared between Cohort 1 & Cohort 2. The intensity of difference between cohorts at every timepoint was determined and the maximal percentage of between-groups difference was summarized.
[0308] Table 2. Responder rate [Number (%)] in cohort 1 and cohort 2 over time, with maximal intensity of difference between both cohorts. * Significant inter-cohort difference for responder rate for this outcome . BSL = baseline; Max. = maximal.„ [Number Max. intensity ofRespronders (%)] d ..if.f.erence (% ’ )Outcome Cohort Week 04 Week 08 Week 12 Week 16A^°hOrtJ “Cohort 2)+272 6 (43) 7 (50) 5 (36) 5 (36) At W16SAC 1 4 (27) - 5 (33) 13 (87)* +422 7 (50) - 5 (36) 2 (31) At W16...... . Continuous weekly expressednc-NAM 1 x ii 10 (67) +35 follow-up2 3 (23) At W13MI-CAT(V) 1 2 (13) 12 (80)* 5 (33)* 6 (40)* -302 0 (0) 2 (14) 0 (0) 0 (0) At W8CONCLUSION OF PAIN / MOBILITY ASSESSMENT
[0309] Thus, the results show that composition A having a ratio of EPA / DHA of about 0.69:1 allow a significant improvement of mobility in OA cats compared to the control group fed by composition B.
[0310] Composition A induces significant improvements in a validated semi- subjective clinical metrology instrument, MI-CAT(V), and on three different validated objective outcomes, recognized as gold standard for determining improvement in mobility (actimetry), in ground reaction forces (PGA) and in fatigue related to exercise (stairs assay compliance). This is complementary to the high level of safety and acceptability of tested diets.
[0311] It was not expected that clinical effects would be present on all markers, nor that they would persist 4 weeks after the cessation of the experimental diet (at week 16).D. RESULTS OF LIPIDS MEDIATORS a. SPM - DHA : 17-HDOHE pathway:
[0312] 17 HDOHE pathway can be considered as one of the most important mediators pathway in the resolution of inflammation for osteoarthritis.
[0313] The composition A induced a clear activation of the 17 HDOHE pathway. The level of 17 HDOHE induced by composition A is statistically higher than the level induced by composition B at W8 and W12 (Table 3). The same behavior has been observed for Resolvin D5 and the protectin PDX (Table 3). At week 16, the level of 17 HDOHE is still significantly higher in cohort 1 , despite 4 weeks of interruption of composition A (Table 3).Table 3: Statistical summary of the comparison between cats in cohort 1 and cohort 2Table 4: Descriptive summary of the comparison between cats in cohort 1 and cohort 2 regarding the evolution of DHA SPM in the 17-HDOHE pathway. Median results expressed in pg / ml.
[0314] In conclusion, there is a clear activation of the SPMs of the 17 HDOHE pathway, induced by composition A, linked to the high level of DHA. b. SPM - DHA: 14-HDOHE pathway:
[0315] The composition A induced a clear activation of the 14 HDOHE pathway. The level of 14 HDOHE induced by composition A is statistically higher than the levelinduced by composition B at W8 and W12 (Table 5). The same behavior has been observed for the Maresin 1 and the Maresin 2 (Table 5).). At week 16, the level of 14HDOHE is still significantly higher in cohort 1 , despite 4 weeks of interruption of composition A (Table 5).Table 5: Statistical summary of the comparison between cats in cohort 1 and cohort 2 regarding the evolution of DHA SPMs in the 14-HDOHE pathway (o-value).Table 6: Descriptive summary of the comparison between cats in cohort 1 and cohort 2 regarding the evolution of DHA SPM in the 14-HDOHE pathway. Median results expressed in pg / ml.
[0316] In conclusion, there is clear activations of the SPMS’s of the 14 HDOHE pathway induced by composition A, linked to the high level of DHA. c. SPM- EPA : 18-HEPE pathway:
[0317] The composition A induced a clear activation of the 18 HEPE pathway. The level of 18 HEPE induced by composition A is statistically higher at W8 and W12 than the level induced by composition B (Table 7). The same behavior has been observed for the resolvin E1 and the resolvin E2 (Table 7). At week 16, the level of 18HEPE is still significantly higher in cohort 1 , despite 4 weeks of interruption of composition A (Table 7).Table 7: Statistical summary of the comparison between cats in cohort 1 and cohort 2Table 8: Descriptive summary of the comparison between cats in cohort 1 and cohort 2 regarding the evolution of EPA SPMs in the 18-HEPE pathway. Median results presented expressed in pg / ml.
[0318] In conclusion, there is clear activation of the 18 HEPE pathway, induced by composition A. d. SPM - Lipoxins - Omega 6
[0319] The composition A induced a clear activation of Lipoxins LXA4 and LXB4. The level of LXA4 and LXB4 induced by composition A is statistically higher than the level induced by composition B at W8 and W12 (Table 9).Table 9: Statistical summary of the comparison between cats in cohort 1 and cohort 2 regarding the evolution of Lipoxins in cats (p-value).Table 10: Descriptive summary of the comparison between cats in cohort 1 and cohort2 regarding the evolution of Lipoxins. Median results expressed in pg / ml.e. Endocannabinoids
[0320] The composition A induced a clear activation of the omega 3 endocannabinoids (eCBs) pathway. The level of DHEA and EPEA induced by composition A are statistically higher than the level induced by composition B at W8 and W12 (Table 11 ). At week 16, the level of DHEA and EPEA are still significantly higher in cohort 1 , despite 4 weeks of interruption of composition A.Table 11 : Statistical summary of the comparison between cats in cohort 1 and cohort 2 regarding the evolution of DHEA and EPEA (p-value).Table 12: Descriptive summary of the comparison between cats in cohort 1 and cohort 2 regarding the evolution of DHEA and EPEA. Median results expressed in oo / ml.CONCLUSION OF LIPID MEDIATORS
[0321] Thus, the results show that composition A having a ratio of EPA / DHA of about 0.69:1 acts on the resolution of the inflammation in OA cats.EXAMPLE 2: Comparison of the efficacy of the food composition in lipids metabolites of healthy catsA. MATERIAL AND METHODS
[0322] The goal of this study is to evaluate the impact of three different diets (composition C, composition D and composition E) on the secretion of some mediators of the resolution of inflammation, Specialized Pro-resolving Mediators (SPM) and endocannabinoids (eCBs) in healthy cats peripheric blood.
[0323] Three compositions were compared:
[0324] Composition C having an EPA:DHA ratio of 1 .97:1 ,
[0325] Composition D having an EPA:DHA ratio of 0.38:1 , and
[0326] Composition E without EPA and DHA (placebo group).
[0327] The three groups include 10 adult healthy adult cats (BCS in a normal range (more than 3 and less than 7).
[0328] The study was divided into two phases:1) acclimation phase (Week -4 to Baseline): all cats (n=30) received composition E;2) treatment phase (Baseline to Week 8): Cohort 3 (n=10 cats) received composition C, Cohort 4 (n=10 cats) received composition D, and Cohort 5 (n=10 cats) received composition E.
[0329] Cats were fed twice daily with the food compositions. The three food compositions were isocaloric (3700 - 3900 Kcal / kg) and palatable. Composition C, D and E were similar except for the level and the ratio of EPA and DHA.
[0330] Table 13: Key nutritional ingredients of compositions C, D and EOther ingredients; composition C: Protein 35% (89.4 g / Mcal), crude fiber 3% (7.7 g / Mcal), moisture 5.6%, ash 6.5 % (16.6 g / Mcal), other 35.7 % (91.2 g / Mcal). composition D: Protein 35.4% (90.5 g / Mcal), crude fiber 3% (7.7 g / Mcal), moisture 5.7%, ash 6.6 % (16.9 g / Mcal), other 35.1 % (89.8 g / Mcal). composition E: Protein 35.6% (94.5 g / Mcal), crude fiber 6.3% (16.8 g / Mcal), moisture 5.6%, ash 6.5 % (17.3 g / Mcal), other 38.3 % (101.7 g / Mcal).
[0331] Dosage of the plasmatic level of Specialized Pro-Resolving Mediators (SPM) endocannabinoids and pro-inflammatory metabolites were performed at BSL, W4 and W8,. Samples were extracted using oasis HLB 96 wells solid phase extraction (Waters). LC-MS / MS analysis will be performed on UHPLC system (Agilent LC1290 Infinity) coupled to Agilent 6490 triple quadrupole MS (Agilent Technologies) equipped with electro-spray ionization operating in negative mode(Le Faouder, 2013). The following mediators were quantified: 17-HDoHE, Resolvin D5 (RvD5) 14-HDoHE, Maresin 2 and Docosahexaenoyl ethanolamide (DHEA).B. RESULTSTable 14: Descriptive summary comparing compositions C, D and E regarding the evolution of SPMs of interest and endocannabinoid DHEA in cats. Median results expressed in pg / ml.Table 15: Statistical summary comparing Compositions C,D and E regarding the evolution of SPMs of interest and endocannabinoid PHEA in cats, (p-value)
[0332] As shown in table 14, composition D induced a higher plasmatic level of17 HDOHE, RVD5, Maresin 2, and DHEA as compared to composition C and E at Week 4 and Week 8. Those biomarkers are known for their beneficial effects on pain, especially in neuroinflammatory and osteoarthritic pain (Huang et al. Arthritis Rheumatol. 2017; Lima-Garcia Br J Pharmacol. 2011 ; Xu et al. Br J Pharmacol. 2011 ; Valdes et al. Sci Rep. 2017; Baggio et al. J Pain. 2023 ; Luo et al. Front Pharmacol.2019; Lopes et al. Curr Res Neurobiol. 2023 ; Paton et al. EurJ Pain. 2020.EXAMPLE 3: Evaluation of the efficacy of the food composition in lipid metabolites of cats suffering from osteoarthritis vs. Meloxicam (AINS)
[0333] The objective of this test is to compare the efficacy of two different therapeutic approaches in cats suffering from osteoarthritis. Compositions F and G are described below.Composition F is the test diet, composition G is the control diet.
[0334] Table 16: Key nutritional ingredients of compositions F and GProtein total can include glycine, proline and hydroxyproline. The composition F contains 1.6% as fed (4.21 g / Mcal) of hydrolyzed collagen.Other ingredients; Composition A: crude fiber 5% (13.18 g / Mcal), moisture 5.2% , ash 5.1% (13.45 g / Mcal), curcuminoids 0.031% (0.082 g / Mcal), other 44.4% (116,98 g / Mcal). Composition B: crude fiber 5.7% (15.04 g / Mcal), moisture 6% , ash 4,9% (12.93 g / Mcal), curcuminoids 0%, other 41% (108.21 g / Mcal)A. MATERIAL AND METHODS
[0335] This assay was conducted on adult cats with evidence of OA. Both Cohort 6 (n=14 cats) and Cohort 7(n=13 cats) include adult cats, all having radiographic and functional (painful) evidence of hind limb osteoarthritis (OA) previously assessed by radiographs.
[0336] This trial is divided into three phases:
[0337] - Acclimation phase 1 (Day (D) -28 to D-1 ): All cats received composition G. The goal of this phase was to perform a wash out of EPA+DHA sources, to stabilize the effect of diet change and to perform accurate baseline value.
[0338] - Treatment phase 2 (DO to D75): After randomization, Cohort 6 received composition F (DO to D75) + one therapeutic window of Meloxicam(D0-D7). Cohort 7 received composition G (DO to D75) + three therapeutic windows of Meloxicam (D0-D7; D29-D36; D57-D64) . The goal of this phase was to compare the efficacy of composition F to the efficacy of composition G + three therapeutic windows of Meloxicam.
[0339] - Combination phase 3 (D76 to D99): Cohort 6 received composition F + Meloxicam (D76-D83). Cohort 7 received composition G + Meloxicam (D76-D83). The goal of this phase was to compare the efficacy of the addition of composition F + Meloxicam as compared to the administration of Meloxicam alone.
[0340] Posology Meloxicam D0-D7:0.1 mg / kg SID PO the first day and then 0.05 mg / kg SID PO for the remaining 7 days
[0341] Posology Meloxicam D29-D36, D57-D64, D76-D83: 0.05 mg / kg SID PO for 8 daysTable 17: Treatments and diets administered at each group.
[0342] Cats were fed twice daily with complete and balanced dry food for adult cats, formulated to meet the nutritional levels established by the AAFCO (Association of American Feed Control Officials). Both the composition A and B diets were isocaloric (about 3700-3800 Kcal / kg) and palatable.
[0343] A Highly refined pain assessment method, the Montreal Instrument for Cat Arthritis Testing for Veterinarians, MI-CAT(V) has been used to evaluate cats at Baseline (DO), D6, D63, D74 and D81.
[0344] Dosage of the plasmatic level of Specialized Pro-Resolving Mediators (SPM) endocannabinoids and pro-inflammatory metabolites were performed at BSL, W4 and W8. Samples were extracted using oasis HLB 96 wells solid phase extraction (Waters). LC-MS / MS analysis is performed on UHPLC system (Agilent LC1290 10 Infinity) coupled to Agilent 6490 triple quadrupole MS (Agilent Technologies) equipped with electro-spray ionization operating in negative mode (Le Faouder, 2013). The following mediators were quantified: 18 HEPE, 15 HEPE, 17 HDOHE, 14 HDOHE, DHEA and EPEA.B. RESULTS OF PAIN / MOBILITY ASSESSMENT
[0345] Results are represented in Figure 6 and Figure 7.
[0346] Results of this assay show that composition F (black lines) has a better effect on biomechanical alteration measured by MI-CAT (V) on OA in cats than the use of the Meloxicam (Grey lines) (D63) for both populations of allodynic and non-allodynic cats.C. RESULTS OF LIPIDS MEDIATORS
[0347] Results are represented in Tables 18 and 19.Table 18: Statistical summary of the comparison between cats in cohort 6 and cohort 7 regarding the evolution of SPMs and endocannabinoids (p-value).TABLE 19 : Descriptive summary of the comparison between cats in cohort6 and cohort 7 regarding the evolution of SPMs and endocannabinoids. Median results expressed in pg / ml.The data results presented in tables 18 and 19 indicate that the levels of 18 HEPE,15 HEPE, 17 HDOHE, 14 HDOHE, Maresin 2, 15 HETE, DHEA and EPEA are significantly higher in cohort 6 than in cohort 7. The consumption of the Composition F induces a significant increase in all these SPMs. In contrast, consumption of Composition G combined with Meloxicam has no effect on SPMs, or leads to a decrease in these mediators over time.EXAMPLE 4: Illustration of the conversion from q / Mcal to q / kq BW / dav for Functional ComplementA. Cats- Step 1: Determination of the daily caloric allocation in Kcal
[0348] For example, the daily caloric allocation of an obese cat under weight loss program weighting 10 kg is = 42*100711= 216 Kcal / day.
[0349] For example, the daily caloric allocation of a lean cat weighting 2 kg is = 93*20711= 152 Kcal / day.- Step 2: Conversion into a daily quantity of EPA+DHA, EPA or DHA in gram (g / day)
[0350] For example, if we consider a lean cat weighing 2 kg, with a daily caloric allocation of 152 Kcal / day, if the diet contains 20 g / Mcal of EPA+DHA, the quantity received per day is = (152*20) / 1000 = 3,0447 g / day of EPA+DHA
[0351] For example, if we consider an obese cat under weight loss program weighting 10 kg, with a daily caloric allocation of 216 Kcal / day, if the diet contains 0,1 g / Mcal of EPA+DHA, the quantity received per day is = (216*0,1) / 1000 = 0,0216 g / day of EPA+DHA- Step 3: Conversion into a daily quantity of EPA+DHA, EPA, or DHA in g / kg (BW)
[0352] For example, if we consider a lean cat weighing 2 kg receiving by day3,0447 g / day of EPA+DHA, the quantity in g / Kg (BW) per day received is =3,0447 / 2 = 1 ,5224 g / Kg (BW) per day of EPA+DHA.
[0353] For example, if we consider an obese cat under a weight loss program weighting 10 kg receiving by day 0,0216 g / day of EPA+DHA, the quantity in g / Kg (BW) per day received is =0,0216 / 10 = 0,0022 g / Kg (BW) per day of EPA+DHA.B. Dogs- Step 1: Determination of the daily caloric allocation in Kcal
[0354] For example, the daily caloric allocation of a lean dog, with a current body weight of 2 kg, intact is = 125*2075= 210 Kcal / day.
[0355] For example, the daily caloric allocation of an obese dog, in a body weight loss program, with a current body weight of 80 kg is = 60*800’75= 1605 Kcal / day.- Step 2: Conversion into a daily quantity of EPA+DHA, EPA or DHA in gram (g / day)
[0356] For example, if we consider a dog weighing 2 kg, with a daily intact of 210 Kcal / day, if the diet contains 20 g / Mcal of EPA+DHA, the quantity received by day is = (210*20) / 1000 = 4,2045 g / day of EPA+DHA.
[0357] For example, if we consider a dog weighing 80 kg, with a daily intact of 1605 Kcal / day, if the diet contains 0,1 g / Mcal of EPA+DHA, the quantity received by day is = (1605*0,1) / 1000 = 0,1605 g / day of EPA+DHA.- Step 3: Conversion into a daily quantity of EPA+DHA, EPA, or DHA in g / kg (BW)
[0358] For example, if we consider a dog weighing 2 kg receiving a quantity of4,2045 g / day of EPA+DHA, the quantity in g / Kg (BW) per day received is = 4,2045 / 2 = 2,1022 g / Kg (BW) per day of EPA+DHA.
[0359] For example, if we consider a dog weighing 80 kg receiving a quantity of 0,1605 g / day of EPA+DHA, the quantity in g / Kg (BW) per day received is = 0,1605 / 80 = 0,0020 g / Kg (BW) per day of EPA+DHA.EXAMPLE 5: Evaluation of the impact of a complete diet and a Functional complement in the resolution of inflammationA. MATERIAL AND METHODS
[0360] The goal of this study is to evaluate the impact of two different combinations of compositions (composition H, composition I + composition J) on the secretion of some mediators of the resolution of inflammation, Specialized Pro-resolving Mediators (SPM) and endocannabinoids (eCBs) in healthy cats peripheric blood.
[0361] Two combinations of compositions were compared: Composition H, a complete diet, having an EPA:DHA ratio of 0,48:1. Composition I, a complete diet without EPA and DHA (placebo) + Composition J, a functional complement enrichedin EPA and DHA with a ratio of 0,42:1 . We considered that the effect observed in SPM, is induced by Composition J.
[0362] Cohort 8 includes 10 healthy cats at baseline and W4, the cohort 9 includes 10 healthy cats at baseline and 9 healthy cats at W4 (BCS in a normal range (more than 3 and less than 7).
[0363] The study was divided into two phases:1) acclimation phase (Week -4 to Baseline): all cats (n=19) received composition I;2) treatment phase (Baseline to Week 4): Cohort 8 (n=10 cats) received composition H, Cohort 9 (n=10 cats) received compositions l+J.
[0364] Cats were fed twice daily with the food compositions and functional complement. The two food compositions were isocaloric (3700-3800 Kcal / kg) and palatable. Compositions H and I were similar except for the level and the ratio of EPA and DHA. The quantity of jellies given to cohort 9 was calculated so that the EPA+DHA intake was similar in g / kg (BW) per day in cohorts 8 and 9.Table 20: Key nutritional ingredients of composition H and I (complete diet):Table 21 : Key nutritional ingredients of composition J (Functional Complement). Weight of one jelly = 1 ,6 g.B. PARAMETERS EVALUATED DURING THE STUDY
[0365] Dosage of the plasmatic level of Specialized Pro-Resolving Mediators (SPM) endocannabinoids and pro-inflammatory metabolites were performed at BSL, W4 and W8. Samples were extracted using oasis HLB 96 wells solid phase extraction (Waters). LC-MS / MS analysis is performed on UHPLC system (Agilent LC1290 10 Infinity) coupled to Agilent 6490 triple quadrupole MS (Agilent Technologies) equipped with electro-spray ionization operating in negative mode (Le Faouder, 2013). The following mediators were quantified: 18 HEPE, 15 HEPE, 17 HDOHE, 14 HDOHE, DHEA and EPEA.C. RESULTS
[0366] The data results presented in table 22 indicate that the composition J (cohort 9), after four weeks of consumption, significantly increase the plasmatic level of 18 HERE, 15 HERE, 17 HDOHE, 14 HDOHE, DHEA and EPEA. The results obtained on cohort 9 (functional complement) were compared to those obtained on cohort 8 (diet) and show an equivalence of results for all the mediators.Table 22 Descriptive summary of the comparison between cats in cohort 6 and cohort 7 regarding the evolution of SPMs and endocannabinoids DHEA and EPEA in cats. Median results expressed in pg / ml.Table 23: Statistical summary of the comparison between BSL and D28 of cats in cohort9 regarding the evolution of SPMs and endocannbinoids (p-value).EXAMPLE 6: Evaluation of the efficacy of a food composition on functional parameters in cats suffering from osteoarthritis.A. MATERIAL AND METHODS
[0367] The goal of the study is to evaluate the pain relieving and functional impacts of a nutritionally complete and balanced dry food composition, referred to as Composition K, which include a higher amount DHA than EPA. The study also examines the impact of Composition K on specialized pro-resolving mediators (SPMs) and endocannabinoids.
[0368] This study was a randomized, blinded, placebo- and time-controlled study and comply with the Canadian Council on Animal Care (CCAC) guidelines on laboratory animal facilities - characteristics, design, and development (2003). It has been performed on cats suffering from osteoarthritis.
[0369] Composition K was compared to a control dry food composition (Composition L), excluding EPA and DHA (placebo diet).
[0370] Both Cohort 10 and Cohort 11 include adult cats, all having radiographic and functional (painful) evidence of hind limb osteoarthritis (OA), previously assessed by radiographs.
[0371] The study was divided into three phases:1) Acclimation phase (Week -5 to Baseline): All 29 cats received Composition L;2) Treatment phase (Baseline to Week 14): After randomization, Cohort 10 received Composition K and Cohort 11 continued to receive Composition L;3) Recovery phase (Week 15 to Week 17): Both cohort 10 and Cohort 11 received Composition L.
[0372] Cats were fed twice daily with the food compositions, which were formulated to meet the nutritional levels established by the AAFCO (Association of American Feed Control Officials). Both the food Compositions K and L were isocaloric (about 3700-3800 Kcal / kg) and palatable.Table 24: Key nutritional ingredients of Compositions K and L:B. PARAMETERS EVALUATED DURING THE STUDYCat mobility
[0373] Night-time actimetry monitoring (NAM) activity was recorded by Telemetered locomotor activity to continuously measure cat mobility. For the analyses, NAM recordings were captured between 5:00 PM to 6:58 AM during weekends. This timing sequence was chosen based on previous studies, which found NAM to be more specific, sensitive and responsive to analgesics in 15 osteoarthritic cats (as compared to daylight-time actimetry monitoring). (Guillot et al. Epub 2013; Guillot et al. PLoS One. 2014; Monteiro Epub 2016; Monteiro et al. PLoS One. 2017; Klinck et al. J Feline Med Surg 2018).
[0374] The intensity of activity was collected over the three 14-hours night-time periods in each weekend and summed to give the NAM recording over each weekend. The recording from the first three weekends were discarded.Clinical Metrology Instrument (CMI)
[0375] To evaluate the pain in osteoarthritic cats, it was used a highly refined pain assessment method, the Montreal Instrument for Cat Arthritis Testing for 25 Veterinarians (Klinck et al. 2015; Klinck et al. J Feline Med Surg 2018). The test was performed at baseline (BSL), week 8 (W8), week 12 (W12) and week 17 (W17).Podobarometric gait analysis (PGA)
[0376] PGA uses a pressure-sensitive walkway mattress and measuring peak vertical force (PVF) (Strideway HRSW2® System, Tekscan Inc, Boston, MA, USA). The test was performed at BSL, W8, W12 and W17 (Moreau et al. Res Vet Sci. 2013; Moreau et al. Can Vet J. 2014).Cat fatigue
[0377] Stairs assay compliance (SAC) measuring cat fatigue (Delsart 2022). Test was performed at BSL, W8, W12 and W17.Allodynic cats
[0378] In order to determine if a cat is allodynic or non-allodynic, it is evaluated the Paw withdrawal threshold (PWT) using electronic von Frey esthesiometer measuring tactile allodynia (hypersensitivity). The test was performed at BSL, W8, W12 and W17.
[0379] The allodynia threshold is defined at the lower quartile level for hind limbs and for fore limbs. To be considered as allodynic, a cat needs to have at least two values under the allodynia threshold corresponding to the limb category (hind or fore limbs).EXAMPLE 7: Comparison of the efficacy of a food composition in lipids metabolites of osteoarthritic dogs.A. MATERIAL AND METHODS
[0380] The goal of this study is to evaluate the impact of two different diets (Composition H, Composition I + Composition J) on the secretion of some mediators involved in the resolution of inflammation, specifically Specialized Pro-resolving Mediators (SPM) and endocannabinoids (eCBs), in dogs suffering from osteoarthritis.
[0381] Two combinations of compositions were compared:
[0382] Composition M: a complete diet having an EPA:DHA ratio of 2.3:1
[0383] Composition N: a complete diet having an EPA:DHA ratio of 0.35:1
[0384] Composition O: the control diet which does not containEPA or DHA.
[0385] Cohort 12 includes 15 osteoarthritic dogs, and Cohort 13 includes other 15 osteoarthritic dogs.
[0386] The study was divided into two phases:1) Acclimation phase (Week -4 to Baseline): all dogs (n=30) received Composition O;2) Treatment phase (Baseline to Week 4): Cohort 12 (n=15 dogs) received Composition M, Cohort 13 (n=15 dogs) received Composition N.
[0387] Dogs were fed twice daily with the respective food compositions and functional complements. The three food compositions were isocaloric (3500-3650 Kcal / kg) and palatable. Compositions M, N and O were similar except for the levels and ratios of EPA and DHA.Table 25: Key nutritional ingredients of composition M,N and O:B. PARAMETERS EVALUATED DURING THE STUDY
[0388] The plasmatic level of Specialized Pro-Resolving Mediators (SPM), endocannabinoids, and pro-inflammatory metabolites were measured at baseline (BSL), week 4 (W4) and week 8 (W8). Samples were extracted using Oasis HLB 96 wells solid phase extraction (Waters). LC-MS / MS analysis is performed on UHPLC system (Agilent LC1290 10 Infinity) coupled to Agilent 6490 triple quadrupole MS (Agilent Technologies) equipped with electro-spray ionization operating in negative mode (Le Faouder, 2013). The following mediators were quantified: 18 HEPE, 15 HEPE, 17 HDOHE, RVD3, RVD5, 14 HDOHE, Maresin 2 and DHEA.C. RESULTS
[0389] The data results presented in table 26 indicate that Composition N induces a higher plasmatic level of 18 HEPE, 15 HEPE, 17 HDOHE, RVD3, RVD5, 14 HDOHE, Maresin 2 and DHEA as compared to Composition M, after four weeks of consumption.Table 26: Descriptive summary comparing Compositions M and N regarding the evolution of SPMs of interest and endocannabinoid DHEA and EPEA in dogs (median pg / ml).Table 27: Descriptive summary comparing compositions M and N regarding the evolution of SPMs of interest and endocannabinoid PHEA in dogs (p-value).EXAMPLE 8: Evaluation of the efficacy of the food composition on functional parameters in dogs suffering from osteoarthritisA. MATERIAL AND METHODS
[0390] The goal of the study is to evaluate the pain-relieving and functional impact of a nutritionally complete and balanced dry food composition which includes a higher amount of DHA than EPA (ratio EPA:DHA 0,58:1 ) (Composition Q), on Osteoarthritis (OA) symptoms.
[0391] This study was a randomize, blinded, placebo-and time -controlled study and comply with the Canadian Council on Animal Care (CCAC) guidelines on laboratory animal facilities - characteristics, design, and development (2003). The study was performed on dogs suffering from osteoarthritis.
[0392] Composition Q was compared to a control dry food composition (Composition P), which excludes EPA and DHA (placebo diet).
[0393] Both Cohort 14 and Cohort 15 include adult dogs with radiographic and functional (painful) evidence of OA in appendicular articulations, only or predominantly (compared to front limbs) in their hind limbs, assessed by radiographs and presence of OA disability confirmed by clinical orthopedic examination.
[0394] The study was divided into three phases:1) Acclimation phase for 6 weeks (Week -6 to -1 ): All 40 dogs received Composition P2) Treatment phase W1 to W16 (Week 1 to 16): After randomization, Cohort 14 (20 dogs) received Composition Q, and Cohort 15 (20 dogs) received Composition P3) Recovery phase (Week 17 to Week 20): The two groups received Composition P.
[0395] Dogs were fed twice daily with the food compositions, formulated to meet the nutritional levels established by the AAFCO (Association of American Feed Control Officials). The two food compositions Q and P were isocaloric (about 3550-3600 Kcal / kg) and palatable.Table 28: Key nutritional ingredients of compositions Q et PB. PARAMETERS EVALUATED DURING THE STUDYDog actimetrv (locomotor activity monitoring)
[0396] The actimetry (or locomotor activity monitoring) was assessed using a collar-attached accelerometer-based activity sensor (Actical, Minimitter / Respironics, distributed by Bio-Lynx Scientific Equipment Inc.). The sensor has been maintained in place continously from Week -7 to Week -19, for a total of 26 weeks of follow-up. This period included 7 weeks of baseline data acquisition during the Acclimatation / Baseline phase.
[0397] The dogs have been previously acclimated to wearing the device. The device was set to local time and configured to record one count value every two minutes. The amplitude of each count has been subsequently translated to a numeric value (ranging from 0 to infinity) referring to the intensity count of actimetry. (Moreau and al. Can Vet J. 2014., Rialland and al. Pain. 2014).
[0398] The frequence and the intensity of the movements were collected each day (from Monday to Sunday).
[0399] Motor activity was translated into a numerical value, i.e., the number of AM counts, during the daytime period (DAM, Day-time actimetry monitoring). The sum of the actimetry intensity for each day, and specifically during the exercise period (of 15min), was expressed as the group-average total intensity counts. The analysis was restricted to these exercise periods, which occurred at least 10 times per week.Podobarometric gait analysis (PGA)
[0400] The PGA has been performed using a modular pressure-measurement platform, referred to as the Strideway® System (Tekscan, Boston, MS, USA). This system collected objective data on force, impulse and palmar / plantar pressure data, as well as temporal (time) and spatial (distance) parameters, at a trotting gait velocity within the target range of 1.9 to 2.2 m / s. (Moreau et al. Vet Surg.2010; Rialland et al., Pain. 2014; Moreau et al. Vet. 2014). In the literature, Peak Vertical Force (PVF), measured in kilograms or as a percentage of body weight, (%BW),has been reported as a valid outcome for evaluating limb use (Seibert, R. and al. Vet Surg. 2017). The PVF was initially recorded at the trot in raw values (i.e., kg) and then adjusted according to the body weight distribution, resulting in a normalized PVF expressed as %BW.
[0401] PGA was performed twice at baseline (BSL) (day -5 and day -3), and subsequently at Week 8, Week 12, Week 16 and Week 20).C. RESULTS OF DOG ACTIMETRIE AND PODOBAROMETRIC GAIT (PGA) ASSESSMENT
[0402] Both groups were equally represented for body weight (BW), and radiographic scoring. All presented diets (Compositions Q and P) were well accepted, and no dog presented any significant gastro-intestinal disturbances. a. Dog daytime actimetry monitoring
[0403] Over a baseline period of 7 weeks, followed by16 weeks of monitoring after introducing the Composition Q and Composition P to their respective groups, and a subsequent 3-week recovery period, dogs participated in external activities in couple, groups or individually for a minimum of 150 min per week. The actimetry analysis was restricted to these periods of spontaneous activity. Clearly, the mean daytime actimetry monitoring (DAM) values (50th percentile count) collected during the first baseline period (P1) were similar for both groups. The 50th percentile values reflect the standard level of activity during these external activities, being influenced by the comfort of each dog and the usual needs in mobility expressed at each activity.
[0404] The second period (P2) represents the delay necessary for Composition Q to generate some benefits in mobility.
[0405] During the third period (P3), both groups of dogs showed an increase in mobility, with the presence of a dissociation between both groups. Cohort 14 (in black) (which received the composition Q during the treatment phase) showed a bigger increase in mobility than Cohort 15 (in grey) (Figure 8).
[0406] Statistical analysis using Generalized Linear Mixed Models (GLiMM) demonstrated a significant time effect for both groups (P < 0.001 ), indicating changes in locomotor activity in dogs with osteoarthritis (OA). An intra-group difference at P3 group (P < 0.001) was observed for both groups compared to P1 and P2. Moreover, a significant time x group interaction (Type III analysis; P = 0.048) was demonstrated, and the post-hoc analysis revealed significant specific inter-group difference at P3 (P = 0.040) (figure 9). This was reflected by a significantly higher increase in DAM at P3, for cohort 14 (which received the composition Q during the treatment phase) (+48%), indicating higher locomotor activity associated with improved comfort and mobility compared to Cohort 15. While at P1 , the inter-group difference was about 13%, and the increase in standard activity for cohort 14 at P3 was +35%, in comparison to Cohort 15. b. Podobarometric gait analysis (PGA)
[0407] Figure 10 illustrates the Peak Vertical Force (PVF) of the most affected hind limb, normalized by the dog’s velocity, across different acquisition sessions: Baseline (all dogs fed with composition P), and at 8, 12, 16, and 20 weeks. Modelbased marginal mean values are presented for each acquisition sessions.
[0408] Using linear mixed models, analyses of the PVF values normalized by the dog’s velocity for the most affected hind limb revealed a statistically significant Time (P = 0.043) and Group (P = 0.034) effect, without denoting a statistically significant interaction (P = 0.205) between Time and Group.
[0409] For the Group effect, univariate analyses revealed a significant difference between cohort 14 (in black) (which received composition Q during the treatment phase) and cohort 15 (in grey) at Week 8 (P = 0.033) and Week 20 (P = 0.014). Regarding the Time effect, only cohort 14 showed significant changes overtime (P = 0.045). Specifically, values at Week 20 were higher compared to the Baseline Mean (P = 0.025) as well as to Week 8 (P = 0.016) and Week 12 (P = 0.004). Dogs in cohort 14 demonstrated improved plantar pressure and velocity, indicating a decrease inlameness over time.Figure 11 presents the Peak Vertical Force (kg • s • cm-1) of the most affected hind limb, normalized by the dog’s velocity with model-based marginal mean values expressed as a percentage relatively to the Baseline Mean.
[0410] At Week 20, dogs in Cohort 14 (in black) showed a significant improvement of their osteoarthritis lameness compared to Cohort 15 (in grey) (which received the composition P) which had a deterioration in lameness.D. CONCLUSION
[0411] Thus, the results show that Composition Q, having a ratio of EPA:DHA of about 0,58:1 , significantly improves OA symptoms based on two objectives outcomes. These outcomes, actimetry / locomotor activity and ground reaction forces (PGA), are recognized as the gold standard for determining improvement in mobility.EXAMPLE 9: GENERAL CONCLUSION
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Claims
CLAIMS1 . A food composition for a companion animal comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for use in a method for treating and / or preventing a chronic inflammatory joint disease in a companion animal in need thereof, wherein the mass ratio of EPA to DHA is from about 0.2:1 to about 1 :1 , preferably from about 0.3:1 to about 0.9:1 , and the total amount of EPA and DHA is from about 0.1 g / Mcal to about 20 g / Mcal.
2. The food composition for use according to claim 1 , wherein the food composition includes from about 1.6 mg / Mcal to about 4400 mg / Mcal of curcuminoids.
3. The food composition for use according to claim 1 or 2, wherein the food composition includes from about 0.07 g / Mcal to about 215 g / Mcal of hydrolyzed collagen.
4. The food composition for use according to claim 2, wherein the curcuminoids are selected from curcumin, demethoxycurcumin, bisdemethoxycurcumin and / or tetrahydrocurcumin.
5. The food composition for use according to claim 3, wherein the hydrolyzed collagen is a combination comprising at least glycine, proline and hydroxyproline.
6. The food composition for use according to any one of claims 1 to 5, wherein the food composition includes from about 0.05 g / Mcal to about 10 g / Mcal of EPA, optionally from about 0.05 g / Mcal to 5 g / Mcal of EPA.
7. The food composition for use according to any one of claims 1 to 6, wherein the food composition includes from about 0.05 g / Mcal to about 19 g / Mcal, optionally from about 0.2 g / Mcal to about 10 g / Mcal, of DHA.
8. The food composition for use according to any one of claims 1 to 7, wherein the food composition includes from about 0.5 g / Mcal to about 10 g / Mcal of EPA and DHA.
9. The food composition for use according to any one of claims 1 to 8, wherein a source of EPA and DHA is selected from fish oil, fish meal, algae oil, eggs, oyster, chia seed, walnuts, soybeans, Green Leaped Mussel or a mixture thereof.
10. The food composition for use according to any one of claims 1 to 9, wherein the chronic inflammatory joint disease is selected from osteoarthritis, bursitis, rheumatoid arthritis, juvenile rheumatoid arthritis, infectious arthritis, psoriasis-relatedarthritis or reactive arthritis disease, in particular the chronic inflammatory joint disease consists of osteoarthritis.
11. The food composition for use according to any one of the preceding claims, wherein the companion animal is a canine or a feline.
12. The food composition for use according to claim 11 , wherein the canine is a dog.
13. The food composition for use according to claim 11 or 12, wherein the feline is a cat.
14. The food composition for use according to any one of the preceding claims, wherein the companion animal exhibits signs of central sensitization, signs of allodynia and / or signs of hyperalgesia.
15. The food composition for use according to any one of the preceding claims, wherein the food composition is a nutritionally complete and balanced food composition.
16. The food composition for use according to claim 15, wherein the nutritionally complete and balanced food composition i) is a dry food composition including at least about 2500 kilocalories of metabolizable energy (ME) per kilogram or ii) is a wet food composition including at least about 400 kilocalories of metabolizable energy (ME) per kilogram.
17. The food composition for use according to any one of the preceding claims, wherein the food composition is a functional complement.
18. A food composition comprising:- Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), wherein the food composition includes from about 0.1 g / Mcal to about 20 g / Mcal of EPA and DHA and wherein the mass ratio of EPA to DHA is from about 0.2:1 to about 1 :1 , and- from about 0.07 g / Mcal to about 215 g / Mcal of hydrolyzed collagen.
19. A method for feeding a companion animal, wherein the method includes at least a step of administering to the companion animal a food composition according to claim 18.
20. A nutritionally complete and balanced feline food composition including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for use in a method for treating and / or preventing a chronic inflammatory joint disease in a feline in need thereof, whereinthe mass ratio of EPA to DHA is from about 0.2:1 to about 1 :1 , preferably from about 0.3:1 to about 0.9:1 , and the total amount of EPA and DHA is from about 0.1 g / Mcal to about 20 g / Mcal.21 . The nutritionally complete and balanced feline food composition for use according to claim 20, wherein the food composition includes from about 1.6 mg / Mcal to about 4400 mg / Mcal of curcuminoids.
22. The nutritionally complete and balanced feline food composition for use according to claim 20 or 21 , wherein the food composition includes from about 0.07 g / Mcal to about 215 g / Mcal of hydrolyzed collagen.
23. The nutritionally complete and balanced feline food composition for use according to claim 21 , wherein the curcuminoids are selected from curcumin, demethoxycurcumin, bisdemethoxycurcumin and / or tetrahydrocurcumin.
24. The nutritionally complete and balanced feline food composition for use according to claim 22, wherein the hydrolyzed collagen is a combination comprising at least glycine, proline and hydroxyproline.
25. The nutritionally complete and balanced feline food composition for use according to any one of claims 20 to 24, wherein the food composition includes from about 0.05 g / Mcal to about 10 g / Mcal of EPA, optionally from about 0.05 g / Mcal to 5 g / Mcal of EPA.
26. The nutritionally complete and balanced feline food composition for use according to any one of claims 20 to 25, wherein the food composition includes from about 0.05 g / Mcal to about 19 g / Mcal, optionally from about 0.2 g / Mcal to about 10 g / Mcal, of DHA.
27. The nutritionally complete and balanced feline food composition for use according to any one of claims 20 to 26, wherein the food composition includes from about 0.5 g / Mcal to about 10 g / Mcal of EPA and DHA.
28. The nutritionally complete and balanced feline food composition for use according to any one of claims 20 to 27, wherein a source of EPA and DHA is selected from fish oil, fish meal, algae oil, eggs, oyster, chia seed, walnuts, soybeans, Green Leaped Mussel or a mixture thereof.
29. The nutritionally complete and balanced feline food composition for use according to any one of claims 20 to 28, wherein the chronic inflammatory joint disease is selected from osteoarthritis, bursitis, rheumatoid arthritis, juvenile rheumatoidarthritis, infectious arthritis, psoriasis-related arthritis or reactive arthritis disease, in particular the chronic inflammatory joint disease consists of osteoarthritis.
30. The nutritionally complete and balanced feline food composition for use according to any one of claims 20 to 29, wherein the feline is a cat.
31. The nutritionally complete and balanced feline food composition for use according to any one of claims 20 to 30, wherein the feline, in particular the cat, exhibits signs of central sensitization, signs of allodynia and / or signs of hyperalgesia.
32. The nutritionally complete and balanced food composition for use according to any one of claims 1 to 31 , wherein the food composition i) is a dry food composition including at least about 2500 kilocalories of metabolizable energy (ME) per kilogram or ii) is a wet food composition including at least about 400 kilocalories of metabolizable energy (ME) per kilogram.
33. A nutritionally complete and balanced food composition comprising:- Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), wherein the food composition includes from about 0.1 g / Mcal to about 20 g / Mcal of EPA and DHA and wherein the mass ratio of EPA to DHA is from about 0.2:1 to about 1 :1 , and- from about 0.07 g / Mcal to about 215 g / Mcal of hydrolyzed collagen.
34. A method for feeding a feline, wherein the method includes at least a step of administering to the feline a nutritionally complete and balanced food composition according to claim 33.
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