Compositions comprising a turmeric extract for use in the treatment of inflammatory and / or degenerative joint disorders by modulation of the endocannabinoid system

Abstract

The present invention relates to compositions comprising a mixture comprising or, alternatively, consisting of a turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol for use in the treatment, preventive and / or curative, of at least one joint pathology of an inflammatory and / or degenerative nature and / or of a symptom associated therewith in human beings, or monogastric animals, by modulation of the receptors and / or enzymes of the endocannabinoid system.

Description

[0001] COMPOSITIONS COMPRISING A TURMERIC EXTRACT FOR USE IN THE TREATMENT OF INFLAMMATORY AND / OR DEGENERATIVE JOINT DISORDERS BY MODULATION OF THE ENDOCANNABINOID SYSTEM

[0002] DESCRIPTION

[0003] The present invention relates to compositions comprising a mixture comprising or, alternatively, consisting of a turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol for use in the treatment, preventive and / or curative, of at least one joint pathology of an inflammatory and / or degenerative nature and / or of a symptom ad associated therewith in human beings, or monogastric animals, by modulation of the receptors and / or enzymes of the endocannabinoid system.

[0004] BACKGROUND OF THE INVENTION

[0005] Joint pathologies of an inflammatory and / or degenerative nature represent a health problem of major relevance which affects a wide variety of species, negatively impacting on the quality of life, the capacity of movement and, more generally, the overall wellbeing of human beings and pets. These disorders comprise chronic conditions such as osteoarthritis, rheumatoid arthritis and other forms of inflammatory or degenerative arthritis, all having in common a progressive deterioration of joint structures. This translates into motor limitations, chronic pain and, in more severe cases, permanent disability. Joint pathologies may also reduce the efficiency of animal species of economic and productive interest, such as poultry and pigs, where joint health is crucial for maintaining growth and production. Osteoarthritis, in particular, is a chronic condition that is very common in human beings and pets; it manifests itself with the gradual erosion of joint cartilage, a smooth, resistant structure that coats the ends of bones in joints, protecting them from friction and impacts. In monogastric mammals, as in human beings, this degenerative process is often accompanied by chronic inflammations which accelerate tissue damage. In humans, osteoarthritis affects about 7% of the world's population, whereas in pets, such as dogs, it is present in about 20% of the population. Joint disorders are also frequent in animal species intended for food production, such as poultry and pigs, with significant consequences on motor capacity, general health and productivity.

[0006] The technical problem that the present invention addresses and resolves is to provide a composition and a treatment which are effective for the treatment of inflammatory and / or degenerative joint disorders in human beings or monogastric animals.

[0007] In particular, the technical problem that the present invention addresses and resolves is to provide a composition comprising natural ingredients which is capable of reducing joint inflammation and effectively treating inflammatory and / or degenerative joint disorders in human beings or monogastric animals.

[0008] WO2023148668 A1 discloses a formulation comprising curcumin from Curcuma longa, turmeric extract, ginger extract, cinnamon oil extract, and Boswellia serrata extract, wherein the formulation forms a natural matrix comprising polar and non-polar matrices. Said composition is for use in the treatment of joint inflammation. Thymol is not described.

[0009] Document CN115227796 A discloses a formulation for the treatment of scapulohumeral periarthritis which comprises various ingredients, including turmeric, thymol and cinnamon sticks, cassia twig, borneol, Angelica dahurica, Panax notoginseng, eucalyptus, camphor, centipedes, Coptis Coptidis, capsaicin, and emu oil.

[0010] Document CN116966256 A discloses an analgesic liquid of traditional Chinese medicine comprising, in addition to cinnamon oil and turmeric, other further ingredients, such as musk, Wintergreen oil, eucalyptus oil, lavender oil, clove and basil oil, and Angelica dahurica.

[0011] An example of a natural substance capable of acting effectively on joint pain is cannabinoids derived from Cannabis spp., which may be prescribed for arthritis, osteoarthrosis and fibromyalgia.

[0012] However, the therapeutic application of Cannabis spp. or the derived extracts thereof is not always feasible because of legislative restrictions around the world.

[0013] Therefore, it is necessary to identify natural compounds defined as "cannabinoid-like”, which are capable of exerting anti-inflammatory and antioxidant actions.

[0014] Furthermore, it is necessary to provide a mixture and / or a composition which are useful for that purpose, are also easy to prepare and do not require the use of costly machinery and procedures.

[0015] These aims and still others, which will emerge clearly from the detailed description that follows, are reached by the composition comprising a turmeric extract which has the technical features claimed in the appended claims.

[0016] SUMMARY OF THE INVENTION

[0017] A first aspect of the present invention relates to a composition for use in a method of treatment, preventive and / or curative, of at least one joint pathology of an inflammatory and / or degenerative nature or of a symptom associated therewith by modulation of the receptors and / or enzymes of the endocannabinoid system, in a human being, or in a monogastric animal, wherein said composition comprises:

[0018] - a mixture M comprising or, alternatively, consisting of a turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol and,

[0019] - optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient.

[0020] In the composition according to the invention, the mixture M comprises or, alternatively, consists of a turmeric extract, cinnamon oil and thymol.

[0021] Therefore, the object of the invention is a composition for use in a method of treatment, preventive and / or curative, of at least one joint pathology of an inflammatory and / or degenerative nature or of a symptom associated therewith by modulation of the receptors and / or enzymes of the endocannabinoid system, in a human being, or in a monogastric animal, wherein said composition comprises:

[0022] - a mixture M comprising or, alternatively, consisting of a turmeric extract, cinnamon oil and thymol and,

[0023] - optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient.

[0024] Preferably, the composition according to the invention further comprises a controlled-release lipid matrix that embeds or encloses said mixture M and, optionally, an acceptable pharmaceutical or food grade additive and / or excipient.

[0025] This composition aims to reduce joint inflammation, while simultaneously promoting long-term protection and maintenance of joint function and offering significant benefits for the general wellbeing and quality of life of the affected individuals.

[0026] Therefore, the composition according to the present invention is particularly useful in the treatment of pathologies characterised by joint inflammation and, in particular, degeneration of joint cartilage, such as, for example, osteoarthritis.

[0027] Preferably, the composition of the invention is useful in a method of treatment, preventive and / or curative, of at least one joint pathology and / or of a symptom associated therewith, wherein said at least one pathology or symptom associated therewith is selected in the group which comprises or, alternatively, consists of: osteoarthritis, rheumatoid arthritis, psoriatic arthritis, septic arthritis of a non-bacterial nature, gouty arthritis, reactive arthritis, cervical and lumbar arthrosis, synovitis, tendinitis, tenosynovitis, bursitis, ankylosing spondylitis, inflammatory spondyloarthropathies, polyarthritis, systemic lupus erythematosus with joint manifestations, fibromyalgia with musculoskeletal and joint symptoms, arthralgia (joint pain), adhesive capsulitis (frozen shoulder), condensing osteitis, avascular osteonecrosis, spondylolisthesis, joint overload syndrome, patellofemoral syndrome, enthesitis (inflammation of tendon insertion sites), Sjogren's syndrome with joint involvement, carpal tunnel syndrome secondary to joint inflammation, plantar fasciitis, acute and chronic joint pain, joint and muscle stiffness, joint swelling and inflammation, functional limitation of joint mobility, and muscle fatigue and weakness correlated with joint pain.

[0028] Preferably, the composition disclosed in the present invention is for use in a method of treatment, preventive and / or curative, of osteoarthritis.

[0029] A further aspect of the present invention is a composition comprising or, alternatively, consisting of:

[0030] - a mixture M comprising or, alternatively, consisting of a turmeric extract, cinnamon oil and thymol and,

[0031] - optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient.

[0032] Preferably, said composition further comprises a controlled-release lipid matrix that embeds or encloses, preferably within it, said mixture M, wherein said controlled-release lipid matrix comprises or, alternatively, consists of at least one saturated or unsaturated, free or esterified fatty acid having a number of carbon atoms comprised in the C10- C30 range, and / or at least one triglyceride having saturated or unsaturated fatty acid chains having a number of carbon atoms comprised in the C6-C30 range, and / or at least one wax having a number of carbon atoms comprised in the C16-C36 range.

[0033] DESCRIPTION OF THE FIGURES

[0034] The present invention is also better described with the aid of the following figures which are provided solely by way of example and, therefore, do not limit the scope thereof.

[0035] Figure 1 (A-B-C-D-E-F) shows the data of gene expression (on human chondrosarcoma cells) following an inflammatory insult, in the presence of cinnamon essential oil (CAN) and / or turmeric oleoresin (CUR), relative to inflammatory molecules (IL-6, IL-8, NFKB1) and matrix metalloproteinases (MMP1, MMP3, MMP13) involved in the degenerative processes of joints.

[0036] Figure 2 (A-B-C-D) shows the data of gene expression (on human chondrosarcoma cells) following an inflammatory insult, in the presence of cinnamon essential oil (CAN) and / or turmeric oleoresin (CUR), relative to the CB1 and CB2 receptors of the endocannabinoid system, as well as the enzymes DAGL-o and MAGL involved in the metabolism of endocannabinoids.

[0037] Figure 3 (A-B-C-D) shows the data of gene expression of IL-6 and MMP3 following an inflammatory insult, comparing the treatments with CAN, CUR and the combination thereof (CAN+CUR). Also shown are graphs regarding the Bliss independence model, for the calculation of the synergism between the extracts.

[0038] Figure 4 (A-B-C-D) shows the data of gene expression of IL-6 and MMP3 following an inflammatory insult, comparing the treatments with CAN, CUR, the combination thereof (CAN+CUR), TIM and the triple combination thereof (CAN+CUR+TIM). Also shown are graphs regarding the Bliss independence model, for the calculation of the synergism between the extracts.

[0039] Figure 5 (A-B-C-D-E-F) shows the data of gene expression (on human chondrosarcoma cells) following an inflammatory insult, in the presence of turmeric oleoresin (CUR) and / or thymol (TIM), relative to inflammatory molecules (IL-6, IL-8, NFKB1) and matrix metalloproteinases (MMP1, MMP3, MMP13) involved in the degenerative processes of joints.

[0040] Figure 6 (A-B-C-D) shows the data of gene expression (on human chondrosarcoma cells) following an inflammatory insult, in the presence of turmeric oleoresin (CUR) and / or thymol (TIM), relative to the CB1 and CB2 receptors of the endocannabinoid system, as well as the enzymes DAGL-o and MAGL involved in the metabolism of endocannabinoids.

[0041] Figure 7 (A-B-C-D) shows the data of gene expression of IL-6 and MMP3 following an inflammatory insult, comparing the treatments with CUR, TIM and the combination thereof (CUR+TIM). Also shown are graphs regarding the Bliss independence model, for the calculation of the synergism between the extracts.

[0042] Figure 8 (A-B-C-D) shows the data of gene expression of IL-6 and MMP3 following an inflammatory insult, comparing the treatments with CAN, CUR_A (oleoresin), CUR_B (turmeric extract), and the combination (CUR+ CUR_A and CUR+ CUR_B), according to what is described in example 3. Also shown are graphs regarding the Bliss independence model, for the calculation of the synergism between the extracts.

[0043] DETAILED DESCRIPTION OF THE INVENTION

[0044] The subject matter of the present invention relates to a composition for use (briefly, composition of the invention) in a method of treatment, preventive and / or curative, of at least one joint pathology of an inflammatory and / or degenerative nature and / or of a symptom associated therewith by modulation (or modulation or increase or decrease of gene expression) of the receptors and / or enzymes of the endocannabinoid system, in a human being, or in a monogastric animal, wherein said composition comprises:

[0045] - a mixture M (briefly, mixture M of the invention) comprising or, alternatively, consisting of a turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol and,

[0046] - optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient.

[0047] The subject matter of the present invention relates to a composition for use (briefly, composition of the invention) in a method of treatment, preventive and / or curative, of at least one joint pathology of an inflammatory and / or degenerative nature and / or of a symptom associated therewith by modulation (or modulation or increase or decrease of gene expression) of the receptors and / or enzymes of the endocannabinoid system, in a human being, or in a monogastric animal, wherein said composition comprises or, alternatively, consists of:

[0048] - a mixture M (briefly, mixture M of the invention) comprising or, alternatively, consisting of a turmeric extract of cinnamon oil and thymol and,

[0049] - optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient.

[0050] The composition for use according to the invention comprises a mixture M which comprises or, alternatively, consists of a turmeric extract, cinnamon oil and thymol.

[0051] Preferably, the composition for use according to the invention comprises a mixture M which comprises or, alternatively, consists of a turmeric extract in the form of an oleoresin and cinnamon oil and thymol.

[0052] Said turmeric extract is an extract obtained from the root of the plant Curcuma longa L. and comprises, as the active ingredient, curcumin and, optionally, other bioactive compounds such as demethoxycurcumin and bisdemethoxycurcumin.

[0053] Said curcumin (e.g. preferably, having CAS No. 458-37-7), demethoxycurcumin (e.g. preferably, having CAS No. 22608-11-3) and bisdemethoxycurcumin (e.g. preferably, having CAS No. 33171-05-0) are curcuminoids.

[0054] In the context of the present invention, the term "curcuminoids" is understood to indicate the chemical compounds making up the pigment extracted from Curcuma longa, or the analogues or derivatives thereof of natural or synthetic origin.

[0055] Said curcuminoids may be present in a phytocomplex.

[0056] Said curcumin and said demethoxycurcumin and bisdemethoxycurcumin, optionally present, may be present in a phytocomplex.

[0057] For example, the turmeric extract may be used in the form of an oleoresin, standardised extract, powder or other extraction forms containing curcumin and / or curcuminoids; preferably, said turmeric extract is in the form of an oleoresin. Furthermore, the composition can comprise purified forms of curcumin and / or curcuminoids, obtained by means of purification techniques. Such purified forms may include isolated curcumin, high-purity curcumin and / or preparations that comprise mixtures of purified curcumin and other purified curcuminoids.

[0058] Preferably, the composition comprises a turmeric extract in the form of a turmeric oleoresin (e.g. preferably, having CAS No. 84775-52-0).

[0059] Turmeric oleoresin is a natural extract obtained from the root of Turmeric {Curcuma longa L), a perennial plant belonging to the family Zingiberaceae.

[0060] For example, the extraction can take place using acetone, ethyl acetate and / or hexane and the purification, for example, using isopropanol or ethyl acetate or mixtures of solvents, such as, for example, isopropanol / ethanol or ethyl acetate / hexane. The solvents can be removed under vacuum.

[0061] Preferably, the turmeric oleoresin comprises curcumin, the main active ingredient of turmeric extract and, optionally, demethoxycurcumin and bisdemethoxycurcumin.

[0062] More preferably, the turmeric oleoresin comprises curcumin and demethoxycurcumin and bisdemethoxycurcumin. Preferably, said turmeric extract, more preferably in the form of a turmeric oleoresin, comprises a concentration of curcuminoids of at least 20% by weight relative to the total weight of the turmeric extract.

[0063] Preferably, said turmeric extract has a concentration of curcuminoids ranging from 20% to 95% by weight, preferably from 30% to 70% by weight, more preferably from 35% to 50% by weight relative to the total weight of the extract.

[0064] Preferably, said turmeric extract comprises curcumin.

[0065] Preferably, the curcumin can be present in said turmeric extract in an amount ranging from 10% to 90%, preferably from 20% to 60%, more preferably from 40% to 50% by weight relative to the total weight of the turmeric extract.

[0066] Preferably, said turmeric extract, more preferably in the form of a turmeric oleoresin, comprises, in addition to curcumin, also demethoxycurcumin and / or bisdemethoxycurcumin.

[0067] More preferably, said turmeric extract, more preferably in the form of a turmeric oleoresin, in addition to curcumin, also comprises demethoxycurcumin and bisdemethoxycurcumin.

[0068] For example, in a turmeric extract comprising 29.40 ± 4.20% (w / w) of total curcuminoids, curcumin may be, for example, present as 18.20 ± 2.60% (w / w) curcumin (CUR), 6.01 ± 0.85% (w / w) demethoxycurcumin and 5.22 ± 0.74% (w / w) bisdemethoxycurcumin.

[0069] In the context of the present invention, the amounts expressed by weight or as a percentage volume imply a natural tolerance, even where not expressly specified, given by the method and equipment used or the experience of the operator who has performed the measurements; the tolerance to be considered may be, for example, in the order of ±0.05% and up to ±0.1 %, even where not expressly specified.

[0070] An example of a commercial turmeric oleoresin product, which can be present in the composition for use according to the present invention, is the product sold by Universal Oleoresins at VIII / 946 Navaratna House Jawahar Road, Kochi 682002, India. The turmeric oleoresin appears as a yellow or orange viscous liquid obtained by extraction, with a solvent (for example, ethyl acetate), from the rhizomes of Curcuma longa.

[0071] Said product has a minimum curcumin concentration of 35% by weight, relative to the total weight of the extract. Preferably, the curcumin can be present in said turmeric extract in an amount ranging from 10% to 90%, preferably from 20% to 60%, more preferably from 40% to 50% by weight relative to the total weight of the turmeric extract.

[0072] An example of commercial resin extract product is the product supplied by Aplantis GmbH, which appears as a fine, yellow powder with a particle size of 100% through an 80 mesh sieve and a concentration of curcuminoids equal to 95% (concentration of curcumin > 70%), as measured by HPLC.

[0073] The turmeric extract is obtained from the roots of the plant Curcuma longa L by extraction in water and ethanol (20:80) as solvents, with an extraction ratio for example of 25:1 .

[0074] The extraction ratio, also known as drug-extract ratio (DER), expresses the amount of raw plant material necessary to produce a finished extract. For example, a 10:1 ratio means that 10 kg of raw herb are necessary to create 1 kg of extract.

[0075] The at least one joint pathology of an inflammatory and / or degenerative nature, and / or a symptom associated therewith, is selected in the group that comprises or, alternatively, consists of joint pathologies of an inflammatory and / or degenerative nature which affect human beings or monogastric animals.

[0076] In carnivores and omnivores, there is one stomach (monogastric animals), whereas among herbivores, equids are monogastric and ruminants are polygastric. In polygastric animals, the glandular stomach or abomasum, structurally similar to the glandular stomach of monogastric animals, is preceded by three sacks, known as "prestomachs”.

[0077] The term "monogastric animal” indicates animals having only one stomach that appears as an ample dilation of the digestive tube downstream of the oesophagus, with which it communicates by means of the cardiac orifice and continues with the small intestine through a second orifice.

[0078] In the context of the present invention, the term "monogastric animal(s)” includes dogs and pigs.

[0079] Advantageously, the compositions of the present invention show interesting therapeutic properties for the treatment, preventive and / or curative, of joint pathologies of an inflammatory and / or degenerative nature by virtue of the ability of turmeric extract, cinnamon oil and thymol to modulate gene expression, in chondrocytes, of endocannabinoid system (ECS) receptors, such as cannabinoid-1 (CB1) and cannabinoid-2 (CB2), and / or of endocannabinoid system (ECS) enzymes, and to reduce the level of pro-inflammatory markers (IL-6, IL-8, NFKB1) and metalloproteinases (MMP1 , MMP3, MMP13) (see the experimental section).

[0080] Preferably, the composition for use of the present invention is useful in a method of treatment, preventive and / or curative, of at least one joint pathology of an inflammatory and / or degenerative nature and / or of a symptom associated therewith selected in the group that comprises or, alternatively, consists of: osteoarthritis, rheumatoid arthritis, psoriatic arthritis, septic arthritis of a non-bacterial nature, gouty arthritis, reactive arthritis, cervical and lumbar arthrosis, synovitis, tendinitis, tenosynovitis, bursitis, ankylosing spondylitis, inflammatory spondyloarthropathies, polyarthritis, systemic lupus erythematosus with joint manifestations, fibromyalgia with musculoskeletal and joint symptoms, arthralgia (joint pain), adhesive capsulitis (frozen shoulder), condensing osteitis, avascular osteonecrosis, spondylolisthesis, joint overload syndrome, patellofemoral syndrome, enthesitis (inflammation of tendon insertion sites), Sjogren's syndrome with joint involvement, carpal tunnel syndrome secondary to joint inflammation, plantar fasciitis, acute and chronic joint pain, joint and muscle stiffness, joint swelling and inflammation, functional limitation of joint mobility, and muscle fatigue and weakness correlated with joint pain.

[0081] More preferably, said composition comprising a mixture M comprising or, alternatively, consisting of a turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol and, in particular both cinnamon oil and thymol and, optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient is advantageously used in a method of treatment, preventive and / or curative, of osteoarthritis.

[0082] Preferably, the composition for use according to the invention comprises a mixture M which, in addition to turmeric extract and thymol, comprises cinnamon oil.

[0083] Preferably, said cinnamon oil comprises an amount of trans-cinnamaldehyde ranging from 50% to 90% (w / w), preferably from 60% to 80% (w / w), more preferably from 70% to 80% (w / w), for example 73% (w / w). An example of cinnamon oil that can be present within the composition for use according to the invention is the cinnamon oil sold by Frey & Lau GmbH, which appears as an orange liquid with a relative density (d20 / 4) ranging from 1.016 to 1.036, for example 1.0263, as measured by means of FL EuAB method 2.2.5.

[0084] Said cinnamon oil has an optical rotation (a20) ranging from -7 to +3°, preferably from -5 to 2°, for example -1.7°, as measured by means of FL EuAB method 2.2.7.

[0085] Furthermore, said cinnamon oil has a refraction index (nD20) ranging from 1.500 to 1.600, preferably from 1.550 to 1.600, for example 1.5899, as measured by FL EuAB method 2.2.6.

[0086] The cinnamon oil, for example the cinnamon oil marketed by Frey & Lau GmbH, may comprise, as active compounds, one or more of the following active compounds: 1 ,8-cineole, linalool, beta-caryophyllene, trans- cinnamaldehyde, eugenol, trans-2-methyl-cinnamaldehyde, coumarin, and benzyl benzoate.

[0087] Said cinnamon oil marketed by Frey & Lau GmbH comprises an amount of trans-cinnamaldehyde ranging from 50% to 90% (w / w), preferably from 60% 80% (w / w), more preferably from 70% to 80% (w / w), for example 73% (w / w).

[0088] Preferably, the composition for use according to the invention comprises a mixture M which, in addition to a turmeric extract, comprises thymol.

[0089] Thymol is a monoterpene phenol present in abundant amounts in plants of the genus Thymus.

[0090] Thymol has the formula C10H14O and a molecular weight of 150.22 g / mol.

[0091] In the context of the present invention, the thymol can be obtained from a thyme extract or a thyme essential oil, or it can be a chemically synthesised molecule, that is, a "nature-identical molecule”.

[0092] In the context of the present invention, the expression "nature-identical molecules” is understood to indicate and include molecules equivalent to the active compounds present in natural extracts or phytocomplexes but produced through chemical synthesis.

[0093] An example of thymol that can be present within the composition according to the invention is the product having the name "Thymol > 98.5”, marketed by Sigma-Aldrich and having CAS No. 89-83-8.

[0094] This product appears as a powder or crystals and comprises thymol with a purity > 98.5%.

[0095] The composition for use according to the invention comprises a mixture M which comprises or, alternatively, consists of turmeric extract, cinnamon oil and thymol.

[0096] In the composition comprising turmeric extract and cinnamon oil and thyme, said turmeric extract, said cinnamon oil and said thymol preferably have one or more of the above-described features.

[0097] In other words, said turmeric extract comprises curcumin and, optionally, demethoxycurcumin and bisdemethoxycurcumin, for example present in a phytocomplex.

[0098] More preferably, said turmeric extract is in the form of a turmeric oleoresin. Said turmeric extract, preferably turmeric oleoresin, comprises curcumin in an amount ranging from 10% to 90%, preferably from 20% to 60%, more preferably from 40% to 50% by weight relative to the total weight of the turmeric extract.

[0099] Said cinnamon oil can have a relative density (d20 / 4) ranging from 1.016 to 1.036, for example 1.0263 measured by means of FL EuAB method 2.2.5, an optical rotation (a20) ranging from -7 to +3°, preferably from -5 to 2°, for example -1 .7°, as measured by means of FL EuAB method 2.2.7, and a refraction index (nD20) ranging from 1 .500 to 1.600, preferably from 1.550 to 1.600, for example 1.5899, as measured by method FL EuAB 2.2.6.

[0100] Furthermore, said cinnamon oil, for example the cinnamon oil marketed by Frey & Lau GmbH, may comprise, as active compounds, one or more of the following active compounds: 1 ,8-cineole, linalool, beta-caryophyllene, trans- cinnamaldehyde, eugenol, trans-2-methyl-cinnamaldehyde, coumarin, and benzyl benzoate.

[0101] In the context of the present invention, the thymol can be obtained from a thyme extract or a thyme essential oil, or it can be a chemically synthesised molecule, that is, a "nature-identical molecule”.

[0102] An example of thymol that can be present within the composition according to the invention is the product having the name "Thymol > 98.5”, marketed by Sigma-Aldrich and having CAS No. 89-83-8.

[0103] Said product appears as a powder or crystals and comprises thymol with a purity > 98.5%.

[0104] In addition to a turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol and turmeric extract, the mixture M within the composition for use according to the present invention can further comprise one or more further active ingredients, described below.

[0105] Preferably, the mixture M can comprise a further first active ingredient, for example deriving from a phytocompound (botanicals), selected in group (I) comprising or, alternatively, consisting of: boswellic acid, rosmarinic acid, harpagoside, alpha-pinene (C10H16, such as e.g., preferably, having CAS No. 80-56-8), alpha-thujone (C10H16O, such as e.g., preferably, having CAS No. 546-80-5), anethole (C10H12C, such as e.g., preferably, having CAS No. 104-46-1), anthocyanins, apigenin (C15H10C5, such as e.g., preferably, having CAS No. 520-36-5), betacaryophyllene (C15H24, such as e.g., preferably, having CAS No. 87-44-5), camphor (C10H16C, such as e.g., preferably, having CAS No. 76-22-2), capsaicin (C18H27NO3, CAS No. 404-86-4), carvacrol (C10H14C, such as e.g., preferably, having CAS No. 499-75-2), catechins, cinnamaldehyde (C9H8O, such as e.g., preferably, having CAS No. 104-55-2), diallyl disulfide (C6H10S2, such as e.g., preferably, having CAS No. 2179-57-9), eugenol (C10H12C2, such as e.g., preferably, having CAS No. 97-53-0), 6-gingerol (C17H26O4, such as e.g., preferably, having CAS No. 23513-14-6), gamma-terpinene (C10H16, such as e.g., preferably, having CAS No. 99-85-4), linalool (C10H18C, CAS No. 78-70-6), limonene (C10H16, such as e.g., preferably, having CAS No. 138-86-3), menthol (C10H20C, such as e.g., preferably, having CAS No. 89-78-1), p-cymene (C10H14, such as e.g., preferably, having CAS No. 99-87-6), polyphenols, tannins, terpineol (C10H18C, such as e.g., preferably, having CAS No. 98-55-5), thymol (C10H14C, such as e.g., preferably, having CAS No. 89-83-8), vanillin (C8H8O3, such as e.g., preferably, having CAS No. 121-33-5), verbascoside (C29H36O15, such as e.g., preferably, having CAS No. 61276-17-3) and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495-60-3), and mixtures thereof.

[0106] In the context of the present invention, the turmeric extract, cinnamon oil and / or thymol and said further first active compound (botanicals) selected in group (I) can be in the form of essential oils, oleoresins or plant extracts comprising the above-described molecules.

[0107] An example of a product containing boswellic acid is the product sold by PhytoLab GmbH & Co. KG Dutendorfer Str. 5-791487 Vestenbergsgreuth, Germany, which appears as a powder comprising an amount of boswellic acid (having, e.g., CAS No. 471-66-9), in particular alpha-boswellic acid, > 90%, preferably > 95%, for example 97% or 98%, as measured by HPLC, and an amount of water > 0.1 %, preferably > 0.2%, more preferably > 0.3%, as measured by coulometric titration (Ph. Eur. 10.0., 2.5.32, SOP 304291 Vers. 2018-01).

[0108] An example of a product containing harpagoside is the product sold by PhytoLab GmbH & Co. KG Dutendorfer Str. 5-791487 Vestenbergsgreuth, Germany, which appears as a white powder. The product comprises an amount of harpagoside (having, e.g., CAS NO.19210-12-9) > 90%, preferably > 95%, more preferably > 98%, as measured by HPLC, and an amount of water > 0.5%, preferably > 0.5%, more preferably > 2%, as measured by coulometric titration (Ph. Eur. 10.0., 2.5.32, SOP 304291 Vers. 2018-01).

[0109] An example of a product containing alpha-pinene is the product sold by PhytoLab GmbH & Co. KG Dutendorfer Str. 5-7 91487 Vestenbergsgreuth, Germany, which appears as a powder. The product comprises an amount of harpagoside (having, e.g., CAS No. 80-56-8) > 90%, preferably > 95%, more preferably > 98%, as measured by method 1 (% AU), SOP 401018, and an amount of water < 1 %, preferably < 0.5%, for example <0.2% as measured by coulometric titration (Ph. Eur. 10.0., 2.5.32, SOP 304291 Vers. 2018-01).

[0110] An example of a product containing anethole is the product sold by Sigma Aldrich, which appears as a transparent liquid in a vial and has an amount of anethole (having, e.g., CAS No. 4180-23-8) > 99%, for example 99.4%, as measured by HPLC, and an amount of water > 0.02%, preferably > 0.05%, for example 0.06 %, as measured by Karl Fischer titration.

[0111] An example of a product containing apigenin (having, e.g., CAS No. 520-36-5) is the product sold by Sigma Aldrich, which appears as a light yellow powder comprising 100% apigenin.

[0112] An example of a product containing beta-caryophyllene is the product sold by PhytoLab GmbH & Co. KG Dutendorfer Str. 5-791487 Vestenbergsgreuth, Germany, which appears as a transparent liquid and comprises an amount of beta-caryophyllene (having, e.g., CAS No.87-44-5) > 90%, preferably > 95%, more preferably > 96%, for example 96.5% as measured by HPLC, and an amount of water < 1 %, preferably < 0.5%, for example < 0.4% as measured by coulometric titration (Ph. Eur. 10.0., 2.5.32, SOP 304291 Vers. 2018-01).

[0113] An example of a product containing camphor is the product sold by PhytoLab GmbH & Co. KG Dutendorfer Str. 5- 7 91487 Vestenbergsgreuth, Germany, which appears as a white powder soluble in chloroform or ethanol 96%, and is slightly soluble in water. The amount of camphor (having, e.g., CAS No. 76-22-2) present in the product is > 90%, preferably > 95%, more preferably > 97%, for example about 98%, as measured by method 1 (% AU), SOP 400778, and an amount of water < 0.8%, preferably < 0.5%, more preferably < 0.2% as measured by coulometric titration (Ph .Eur. 10.0., 2.5.32, SOP 304291).

[0114] An example of a product containing capsaicin is the product sold by Sigma Aldrich which appears as a white powder that has an amount of capsaicin (having, e.g., CAS No. 404-86-4) > 50%, preferably > 60%, for example 60.6% or 60.8%, as measured by HPLC, and an amount of impurities > 30%, for example 38.6%, as measured by HPLC. The product shows a loss on drying for example of 0.02%.

[0115] An example of a product containing carvacrol is the product sold by PhytoLab GmbH & Co. KG Dutendorfer Str. 5- 791487 Vestenbergsgreuth, Germany, which appears as a yellow and comprises an amount of carvacrol (having, e.g., CAS No. 499-75-2), measured by means of method 1 (% AU) SOP 400991 , > 90%, preferably > 95%, more preferably > 98%, for example 100%, and an amount of water < 0.8%, preferably < 0.5%, more preferably < 0.4% as measured by coulometric titration (Ph. Eur. 10.0., 2.5.32, SOP 304291).

[0116] An example of a product containing catechins is the product sold by PhytoLab GmbH & Co. KG Dutendorfer Str. 5- 791487 Vestenbergsgreuth, Germany, which appears as a powder soluble in methanol and in water. This product comprises an amount of catechin (having, e.g., CAS No. 154-23-4) > 98%, preferably > 99%, for example 100%, as measured by HPLC, and an amount of water > 0.5%, preferably 0.8%, for example 1 %, as measured according to Ph. Eur. 9.4., 2.5.32, SOP 304291.

[0117] An example of a product containing cinnamaldehyde is the product sold by Sigma Aldrich, which appears as a transparent liquid comprising an amount of cinnamaldehyde (having, e.g., CAS No. 14371-10-9) > 95%, more preferably > 97%, for example 98.8% as measured by HPLC, and an amount of water > 0.1 %, preferably > 0.2%, for example 0.26%, as measured by Karl Fischer titration.

[0118] An example of a product containing diallyl disulfide is the product sold by Sigma Aldrich, which appears as a transparent liquid with a purity (GO AREA %) > 96%, more preferably > 97%, for example 99%.

[0119] The diallyl disulfide has, for example, CAS No. 2179-57-9.

[0120] An example of a product containing eugenol is the product sold by Sigma Aldrich which appears as a transparent liquid comprising 100% eugenol (having, e.g., CAS No. 97-53-0).

[0121] An example of a product containing 6-gingerol is the product sold by PhytoLab GmbH & Co. KG Dutendorfer Str. 5-7 91487 Vestenbergsgreuth, Germany, which appears as a yellow oil soluble in acetonitrile and in ethanol and insoluble in water. The product comprises 6-gingerol (having, e.g., CAS No. 23513-14-6) in an amount > 90%, more preferably > 95%, for example about 98% as measured by HPLC, and an amount of water < 0.8%, preferably < 0.5%, for example 0.2% as measured according to Ph. Eur. 9.4., 2.5.32, SOP 304291.

[0122] An example of a product containing linalool is the product sold by Sigma Aldrich, which appears as a transparent liquid comprising linalool (having, e.g., CAS No. 78-70-6) with a purity > 98%, more preferably > 99%, for example 99.7%, expressed as GC AREA %.

[0123] An example of a product containing limonene is the product sold by Sigma Aldrich, which appears as a liquid with a purity (GC) of the limonene (having, e.g., CAS No. 5989-27-5) > 99%.

[0124] An example of a product containing menthol is the product sold by Sigma Aldrich, which appears as a crystalline powder comprising L-menthol (preferably having, e.g., CAS No. 2216-51-5) with a purity > 99%, preferably > 99.5%, for example 99.6%.

[0125] An example of a product containing p-cymene is the product sold by PhytoLab GmbH & Co. KG Dutendorfer Str. 5-791487 Vestenbergsgreuth, Germany, which appears as a transparent liquid.

[0126] This product comprises p-cymene (having, e.g., CAS No. 99-87-6) with a purity (GC) > 95%, more preferably > 98%, for example 100%, and an amount of water < 0.2% as measured according to Ph. Eur. 9.4., 2.5.32, SOP 304291.

[0127] Preferably, the composition of the invention can comprise turmeric extract and thymol, turmeric extract and cinnamaldehyde, turmeric extract, cinnamaldehyde and thymol, turmeric extract and carvacrol, or turmeric extract and eugenol, or turmeric extract and menthol, or turmeric extract and linalool (C10H18O, such as e.g., preferably, having CAS No. 78-70-6), or turmeric extract and terpineol (C10H18O, such as e.g., preferably, having CAS No. 98-55-5), or turmeric extract and anthocyanins, or turmeric extract and catechins, or turmeric extract and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495-60-3) and mixtures thereof; or turmeric extract, thymol and capsaicin, or turmeric extract, thymol and cinnamaldehyde, or turmeric extract, apigenin and eugenol. More preferably, the composition of the invention can comprise turmeric extract and thymol and cinnamon oil, turmeric extract and cinnamaldehyde and thymol, turmeric extract and carvacrol and cinnamon oil and thymol, or turmeric extract and eugenol and cinnamon oil and thymol, or turmeric extract and menthol and cinnamon oil and thymol, or turmeric extract and cinnamon oil and thymol and linalool (C10H18O, such as e.g., preferably, having CAS No. 78-70-6), or turmeric extract and cinnamon oil and thymol and terpineol (C10H18O, such as e.g., preferably, having CAS No. 98-55-5), or turmeric extract and cinnamon oil and thymol and anthocyanins, or turmeric extract and cinnamon oil and thymol and catechins, or turmeric extract and cinnamon oil and thymol and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495-60-3) and mixtures thereof; or turmeric extract, thymol and cinnamon oil and capsaicin, or turmeric extract, thymol and cinnamon oil and cinnamaldehyde, or turmeric extract, apigenin and cinnamon oil and thymol and eugenol.

[0128] The mixture M contained in the composition of the invention, in addition to turmeric extract, cinnamon oil and thymol and, optionally, said further first active compound (botanicals) selected in group (I), may further comprise one or more compounds commonly used in the treatment of joint pathologies, selected from group (II) comprising or, alternatively, consisting of: glucosamine sulphate, chondroitin sulphate, methylsulfonylmethane (MSM), hyaluronic acid, hydrolysed collagen, type II collagen, and mixtures thereof; preferably glucosamine sulphate, chondroitin sulphate, MSM and mixtures thereof.

[0129] Said compounds commonly used in the treatment of joint pathologies may be in the form of purified extracts, powders, isolated compounds, standardised extracts, micronized formulations, hydrolysates or in the form of salts, and may further be present as single compounds or in combination, according to therapeutic necessity or formulation preferences.

[0130] An example of a product containing glucosamine sulphate (having, e.g., CAS No. 29031-19-4) is the product sold by Peroxitalia s.r.l., which appears as a crystalline powder with a bulk density of 60 g / ml, a pH (2% aqueous solution) ranging from 3 to 5 and a concentration ranging from 98-102%, as measured by HPLC. The sulphate content ranges from 15.5% to 16.5%.

[0131] An example of a product containing chondroitin sulphate (having, e.g., CAS No. 9082-07-9) is the product sold by Peroxitalia s.r.l., which appears as a white hygroscopic powder with a particle size of 80 mesh, a pH (2% aqueous solution) ranging from 5.5 to 7.5, and a concentration of 90% by weight relative to the total weight of the product, as measured by HPLC. This product has an amount of sulphated ash ranging from 20% to 30% by weight relative to the total weight of the product.

[0132] An example of a product containing methylsulfonylmethane (MSM) is the product sold by Sigma Aldrich, which appears as a white powder comprising methylsulfonylmethane (having, e.g., CAS No. 67-71-0) with a purity > 99%, preferably > 99.5%, for example 99.6%.

[0133] For example, the mixture M within the composition of the invention can comprise turmeric extract and glucosamine sulphate; turmeric extract, glucosamine sulphate and chondroitin sulphate; turmeric extract and MSM; turmeric extract, glucosamine sulphate and MSM; turmeric extract, chondroitin sulphate and MSM; turmeric extract, thymol, cinnamaldehyde, glucosamine sulphate and MSM; turmeric extract, thymol, cinnamaldehyde, chondroitin sulphate and MSM; or turmeric extract, hyaluronic acid and hydrolysed collagen.

[0134] For example, the mixture M within the composition of the invention can comprise further components such as glucosamine sulphate; glucosamine sulphate and chondroitin sulphate; and MSM; glucosamine sulphate and MSM; chondroitin sulphate and MSM; thymol, cinnamaldehyde, glucosamine sulphate and MSM; thymol, cinnamaldehyde, chondroitin sulphate and MSM; or hyaluronic acid and hydrolysed collagen.

[0135] In the mixture M contained in the composition of the present invention, the molar ratio between A and B, wherein: A is turmeric extract and, optionally, at least one or more of said further first active ingredients (botanicals) selected in group (I), whilst B is at least one or more of said compounds commonly used in the treatment of joint pathologies selected from group (I I), is comprised in the range of 1 :500 to 500: 1 , preferably from 1 :300 to 300: 1 , more preferably from 1 : 100 to 100: 1 or from 1 :50 to 50:1 or from 1 : 10 to 10: 1.

[0136] The mixture M contained in the composition of the invention, in addition to turmeric extract, cinnamon oil and thymol, and, optionally, said further first active compound selected in group (I) and / or said compound commonly used in the treatment of joint pathologies from group (II), can further comprise at least a further second active ingredient selected in group (III) consisting of:

[0137] - bacterial strains or probiotic bacterial strains belonging to the genus Lactobacillus, Streptococcus, Leuconostoc, Bifidobacterium, Pediococcus, Enterococcus, Saccharomyces;

[0138] - prebiotics, such as e.g. inulin, lactulose, lactitol, mannooligosaccharides, fructooligosaccharides and galactooligosaccharides, tributyrin, monobutyrin (C7H14O4, such as e.g., preferably, having CAS No. 557-25-5), monolaurin (C15H30O4, such as e.g., preferably, having CAS No. 27215-38-9) and mixtures thereof;

[0139] - salts of metals, such as zinc and copper and / or mixtures thereof;

[0140] - organic acids, salts thereof and / or mixtures thereof;

[0141] - essential fatty acids and Omega-3, such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), derivatives from fish oil or other sources and / or mixtures thereof;

[0142] - vitamins, such as e.g. vitamin D, vitamin C, vitamin and, B group vitamins (e.g. B6, B12), vitamin K and / or mixtures thereof.

[0143] In the context of the present invention, the active ingredients present in the turmeric extract, cinnamon oil and thymol, and the active ingredients (botanicals) selected in group (I) and / or in group (II) and / or in group (III) as described above can be present as nature-identical molecules (Regulation (EC) N 1334 / 2008).

[0144] As mentioned, the expression "nature-identical molecules” is understood to indicate and include molecules equivalent to the active compounds present in natural extracts or phytocomplexes but produced through chemical synthesis.

[0145] Advantageously, the compositions developed by the Applicant can be formulated and prepared in such a way as to allow a gradual, targeted release in the intestine according to the species treated.

[0146] The subject matter of the present invention relates to a composition comprising, in addition to the mixture M which comprises turmeric extract, cinnamon oil and thymol, and optionally one or more further active ingredients selected from group (I) and / or (II) and / or (III) as described above, comprises a controlled-release lipid matrix that embeds said turmeric extract, said at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol and said optional one or more further active ingredients present in the mixture M within the composition of the invention.

[0147] Preferably, said one or more further active ingredients can be selected from group (I) and / or (II) and / or (III) as described in the present invention.

[0148] Said controlled-release lipid matrix comprises or, alternatively, consists of at least one saturated or unsaturated, free or esterified fatty acid having a number of carbon atoms comprised in the C10-C30 range, preferably C14-C24 or C16-C22, and / or at least one triglyceride having saturated or unsaturated fatty acid chains having a number of carbon atoms comprised in the C6-C30 range, preferably C14-C24 or C17-C21 , and / or at least one wax having a number of carbon atoms comprised in the C16-C36 range, preferably C24-C36 or C26-C32; wherein said lipid matrix enables a gastroprotection against the acidic pH of the stomach and assures a controlled release into the intestine of the curcuminoids present in the turmeric extract and the further active ingredients optionally present in the mixture M, according to the species treated and the type of lipid matrix used. The controlled release can take place over a time comprised in an interval of 2 hours to 24 hours, preferably 4 hours to 8 hours.

[0149] "Triglycerides” (or triacylglycerols) are neutral esters of glycerol in which the chains of three long-chain fatty acids are present in the place of the hydrogen atoms of the hydroxyl groups. The length of the fatty acid chains in the common structures of triglycerides can be from 5 to 28 carbon atoms, but 17 and 19 are most common.

[0150] The term "fatty acids” (abbreviated FAs) indicates aliphatic monocarboxylic acids which are prevalently, but not exclusively, long-chain (number of carbon atoms comprised in the C10-C30 range) with an even number of carbon atoms, without branches, and acyclic (i.e. made up of molecules that do not have chains forming a ring). Fatty acids can be saturated (if their molecule only has single C-C bonds) or unsaturated (if they have double C=C bonds).

[0151] The term "waxes” indicates long-chain fatty acid esters with high molecular weight monohydric alcohols. Waxes may be of plant origin or animal origin (beeswax). Beeswax is made up of different compounds, including: hydrocarbons 14%, monoesters 35%, diesters 14%, triesters 3%, hydroxy monoesters 4%, hydroxy polyesters 8%, acid esters 1 %, acid polyesters 2%, free acids 12%, free alcohols 1 %, and unidentified 6%. The main components of beeswax are palmitates, palmitic acid, hydroxypalmitates and oleate esters made up of long chains (30-32 carbon atoms) of aliphatic alcohols, with a 6: 1 ratio between the two main components triacontanyl palmitate (myricyl palmitate) CH3(CH2)29O-CO-(CH2) CH3 and cerotic acid CH3(CH2)24COOH. Beeswax has a melting point of between 62°C and 64°C. Its density at 15°C ranges between 0.958 g / cm3and 0.970 g / cm3. Beeswax may be classified into two large categories: European type and Oriental type. The saponification number is 3-5 for the European type and 8-9 for the Oriental type.

[0152] Said fatty acid comprised in the controlled-release lipid matrix can be a fatty acid, or an ester thereof, hydrogenated or non-hydrogenated, of plant and / or animal origin, preferably a hydrogenated fatty acid of plant and / or animal origin, more preferably a hydrogenated fatty acid of plant origin.

[0153] Said triglyceride comprised in said controlled-release lipid matrix can be a hydrogenated or non-hydrogenated triglyceride of plant or animal origin, preferably a hydrogenated triglyceride of plant and / or animal origin, more preferably a hydrogenated triglyceride of plant origin.

[0154] Said waxes comprised in the controlled-release lipid matrix can be of plant and / or animal origin; preferably beeswax.

[0155] Examples of said fatty acid, triglyceride or wax of plant origin, also in hydrogenated form, are: palm oil, sunflower oil, maize oil, rapeseed oil, peanut oil, soybean oil, olive oil, beeswax, and mixtures thereof.

[0156] Examples of triglycerides of animal origin, also in hydrogenated form, are selected from: chicken fat, hydrogenated chicken fat, beef tallow and pork lard.

[0157] When said controlled-release lipid matrix is present, it embeds the mixture M.

[0158] In this case, the composition for use in a method of treatment, preventive and / or curative, of a joint pathology of an inflammatory and / or degenerative nature or of an associated symptom by modulation of the receptors and / or enzymes of the endocannabinoid system, in a human being, or in a monogastric animal comprises:

[0159] - a mixture M comprising or, alternatively, consisting of turmeric extract; wherein said composition further comprises a controlled-release lipid matrix that embeds or encloses said mixture M which comprises or, alternatively, consists of turmeric extract, cinnamon oil and thymol, wherein said controlled- release lipid matrix comprises or, alternatively, consists of at least one saturated or unsaturated, free or esterified fatty acid having a number of carbon atoms comprised in the C10-C30 range, and / or at least one triglyceride having saturated or unsaturated fatty acid chains having a number of carbon atoms comprised in the C6-C30 range, and / or at least one wax having a number of carbon atoms comprised in the C16-C36 range; wherein said lipid matrix enables a gastroprotection and / or a controlled release into the intestine of the mixture M, preferably of the turmeric extract contained therein; and, optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient.

[0160] It is believed that the activation of the endocannabinoid system (ECS) (receptors, signalling molecules and enzymes involved in the biosynthesis and degradation of ligands) represents a valid approach in the control and regulation of joint inflammation and / or degeneration.

[0161] Cannabinoid receptors, whose main representatives are CB1 and CB2, are present in a large part of the body, also including in the cells located in joints and in cartilage. It has thus been hypothesised that the endocannabinoid system regulates important physiological processes, including the immune response and joint degeneration, and that it contributes to maintaining homeostasis, the delicate internal equilibrium of the body. It follows that an irregular functioning of the endocannabinoid system - in particular the modulation of the gene expression of receptors (CB1 and CB2) and enzymes - plays a decisive role in joint pathologies of both an inflammatory nature and degenerative nature.

[0162] The compositions or mixtures of the present invention do not show any significant side effects and may be administered both to adult human beings and animals, and to developing human beings and animals, as well as to pregnant female animals.

[0163] Finally, the compositions or mixtures of the present invention are easy to prepare and economically advantageous. A further aspect of the present description relates to a method of treatment of at least one joint pathology of an inflammatory and / or degenerative nature and / or of a symptom associated therewith which comprises administering a therapeutically effective amount of the composition or mixture M of the invention to a human or to a monogastric animal.

[0164] Furthermore, the composition or mixture M of the present invention comprising turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol is for use in maintaining the joint health of said human beings or monogastric animals, preferably monogastric mammals, such as dogs.

[0165] Preferably, said monogastric animal is a monogastric mammal, preferably a dog or pig.

[0166] Said monogastric mammals, whether adults or in the weaning stage, which are treatable by means of the compositions or mixtures M of the invention can be selected from: dogs, cats, monkeys, pigs, equines, such as horses and donkeys, rabbits prior to weaning, rodents, such as hamsters, cavies, mice, gerbils, chinchillas, degus, squirrels, guinea pigs and rats; weasels, ferrets and stoats.

[0167] Said non-mammal monogastric animals, adults or in the initial growth stage, which are treatable by means of the compositions or mixtures M of the invention can be selected from: animals of landfowl species (class Aves, preferably of the order Galliformes), such as chickens or other poultry, turkeys, guinea hens, pheasants, peacocks, partridges, quails, doves, turtle doves, geese, common ducks and Muscovy ducks.

[0168] The joint pathologies of an inflammatory and / or degenerative nature which are treatable in a preventive and / or curative manner using the compositions or mixtures M of the invention, are advantageously selected in the group comprising or, alternatively, consisting of: osteoarthritis, rheumatoid arthritis, psoriatic arthritis, septic arthritis of a non-bacterial nature, gouty arthritis, reactive arthritis, cervical and lumbar arthrosis, synovitis, tendinitis, tenosynovitis, bursitis, ankylosing spondylitis, inflammatory spondyloarthropathies, polyarthritis, systemic lupus erythematosus with joint manifestations, fibromyalgia with musculoskeletal and joint symptoms, arthralgia (joint pain), adhesive capsulitis (frozen shoulder), condensing osteitis, avascular osteonecrosis, spondylolisthesis, joint overload syndrome, patellofemoral syndrome, enthesitis (inflammation of tendon insertion sites), Sjogren's syndrome with joint involvement, carpal tunnel syndrome secondary to joint inflammation, plantar fasciitis, acute and chronic joint pain, joint and muscle stiffness, joint swelling and inflammation, functional limitation of joint mobility, and muscle fatigue and weakness correlated with joint pain; said pathology is preferably osteoarthritis; more preferably said joint pathology is osteoarthritis.

[0169] Preferably, said method of treatment, preventive and / or curative, comprises the co-administration of one or more drugs, for human or animal use, commonly used for the treatment of the at least one joint pathology of an inflammatory and / or degenerative nature and / or of a symptom associated therewith, which is the object of treatment. The administration of said one or more drugs commonly used for the treatment of said pathology or of a symptom thereof can take place before, after or simultaneously with the administration of the composition comprising the mixture M or the mixture M as defined in the present invention.

[0170] The compositions or mixtures M of the present invention may be for use as adjuvants of further therapeutic approaches (e.g. drugs) in the treatment of the pathologies specified in the present invention.

[0171] The composition of the invention can comprise the mixture M, comprising a turmeric extract, cinnamon oil and thymol, and, optionally, at least one further ingredient selected from group (I), (II) and / or (III) as described above, in a % by weight comprised in the range from 1% to 80%, preferably from 10% to 50%, more preferably from 15% to 45%, and said controlled-release lipid matrix, according to any one of the embodiments of the invention, in a % by weight comprised in the range from 10% to 80%; preferably from 40% to 60%, more preferably from 45% to 55%, wherein said % are relative to the total weight of the composition.

[0172] The mixture M and the composition containing it are prepared using techniques and apparatus known to the person skilled in the art. In particular, the process for preparing the matrix M provides for mixing, in a mixer or in a container equipped with stirring or mixing and heating means, the turmeric extract and cinnamon oil and thymol, and optionally, one or more of the further ingredients selected from group (I) and / or (II) and / or (III), according to any one of the described embodiments, together with the lipid matrix so that all the compounds and ingredients are embedded within the matrix itself in a single whole.

[0173] The composition as described in the present patent application for the invention can be used as a feed or a feed additive.

[0174] Alternatively, said composition of the invention, according to any one of the described embodiments, can be a pharmaceutical composition, a composition for a medical device, a dietary supplement, a food (or novel food or food for special medical purposes), a composition for a dietary supplement or food, either for human beings or for animals (veterinary products).

[0175] The term "medical device", in the context of the present invention, is used within the meaning according to Legislative Decree No. 46 of 24 February 1997, or according to the new Medical Device Regulation (EU) 2017 / 745 (MDR).

[0176] The term "novel food", in the context of the present invention, is used within the meaning according to the Regulation (EC) 258 / 97.

[0177] Advantageously, the mixtures or compositions of the present invention are formulated for oral use.

[0178] The composition of the present invention can be formulated for oral use in solid form, e.g. granules, flakes, powder, soluble powder or granules, tablets, or capsules; or, alternatively, in liquid form, e.g. selected from: solutions, suspensions, emulsions, liquid dispensable in spray form, or syrups; or, alternatively, in semiliquid form, e.g. selected from: softgel, or gel.

[0179] Preferably, the composition of the invention is in solid form for oral use, e.g. granules, powder or flakes. Advantageously, in order to be effective in the methods of treatment described in the present invention, the compositions of the invention are administered through feed to an animal having need, in a daily dose which comprises turmeric extract in an amount (mg / Kg of feed) comprised in the range from 1 mg / Kg to 5000 mg / kg, preferably from 5 mg / Kg to 2000 mg / Kg, more preferably from 15 mg / Kg to 1000 mg / Kg.

[0180] Alternatively, said composition can be administered directly to a monogastric mammal, such as dogs, or a human being having need in a daily dose which comprises turmeric extract in an amount (mg of composition) comprised in the range from 1 to 6000 mg, preferably from 20 mg to 2000 mg, more preferably from 50 mg to 500 mg.

[0181] The aforesaid daily doses can be administered to the individual in a state of need in one dose (single dose) or in repeated doses, for example two, three or four daily doses.

[0182] Finally, the subject matter of the present invention relates to the use of said feed, feed additive or dietary supplement comprising the composition or mixture M of the present invention, according to one of the described embodiments, for the treatment of osteoarthritis in a human being or monogastric animal; preferably a monogastric mammal, such as dogs.

[0183] In order to achieve the aim of the present invention, the components (or active components) of the mixture M of the invention, namely turmeric extract, and the one or more optional further active ingredients of group (I), (II) and / or (III), can be administered to an animal having need also separately and sequentially, and in any order; for example, in a sequence closely spaced over time (from about 0 minutes to 30 minutes) or in a sequence not closely spaced over time (from 1 hour to about 4 or 6 or 8 or 12 hours), and administered with the same frequency or with different frequencies. When said active components of the mixture M of the invention are administered in a single composition, said single composition corresponds to the composition of the present invention.

[0184] Unless otherwise specified, the expression composition or mixture or anything else which comprises a component in an amount "comprised in a range from x to y” means that said component can be present in the composition or anything else in all the amounts present in said range, even if not explicitly stated, including the endpoints of the range.

[0185] Unless otherwise specified, the indication that a composition "comprises” one or more components or substances means that other components or substances may be present, in addition to the one or ones specifically indicated. Within the scope of the present invention, "method of treatment” means an operation on an individual having need, comprising the administration of the bacterial strain or a composition of the invention, having as its purpose the elimination, reduction / decrease or prevention of a pathology or disease and of its symptoms or disorders.

[0186] The term "therapeutically effective amount” refers to amount of active compound and / or bacterial strain that stimulates the biological or medicinal response in a tissue, system, mammal or human being that is being sought and defined by an individual, researcher, veterinarian, physician or another clinician or health care assistant.

[0187] The subject matter of the present invention relates to a process for preparing the above-described compositions which comprises a step in which oil-in-water emulsions and, separately, water-in-oil emulsions are prepared, said emulsions containing the ingredients of group (I) and / or group (II) and / or group (III) which constitute the mixture for yielding a composition in solid form. The present invention relates to a composition comprising:

[0188] - a mixture M comprising or, alternatively, consisting of a turmeric extract, cinnamon oil and thymol and,

[0189] - optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient.

[0190] In said composition ("composition according to the invention” or "composition of the invention”), said turmeric extract, said cinnamon oil and said thymol preferably have one or more of the above-described features.

[0191] Preferably, the mixture M present in the composition according to the invention further comprises at least a further first active compound, preferably deriving from a phytocompound (botanicals), selected in group (I) comprising or, alternatively, consisting of: boswellic acid, rosmarinic acid, harpagoside, alpha-pinene (C10H16, such as e.g., preferably, having CAS No. 80-56-8), alpha-thujone (C10H16O, such as e.g., preferably, having CAS No. 546-80- 5), anethole (C10H12C, such as e.g., preferably, having CAS No. 104-46-1), anthocyanins, apigenin (C15H10C5, such as e.g., preferably, having CAS No. 520-36-5), beta-caryophyllene (C15H24, such as e.g., preferably, having CAS No. 87-44-5), camphor (C10H16C, such as e.g., preferably, having CAS No. 76-22-2), capsaicin (C18H27NO3, such as e.g., preferably, having CAS No. 404-86-4), carvacrol (C10H14C, such as e.g., preferably, having CAS No. 499-75-2), catechins, diallyl disulfide (C6H10S2, such as e.g., preferably, having CAS No. 2179- 57-9), eugenol (C10H12C2, such as e.g., preferably, having CAS No. 97-53-0), 6-gingerol (C17H26O4, such as e.g., preferably, having CAS No. 23513-14-6), gamma-terpinene (C10H16, such as e.g., preferably, having CAS No. 99-85-4), linalool (C10H18C, such as e.g., preferably, having CAS No. 78-70-6), limonene (C10H16, such as e.g., preferably, having CAS No. 138-86-3), menthol (C10H20C, such as e.g., preferably, having CAS No. 89-78- 1), p-cymene (C10H14, such as e.g., preferably, having CAS No. 99-87-6), polyphenols, tannins, terpineol (C10H18C, such as e.g., preferably, having CAS No. 98-55-5), thymol (C10H14C, CAS No. 89-83-8), vanillin (C8H8O3, such as e.g., preferably, having CAS No. 121-33-5), verbascoside (C29H36O15, such as e.g., preferably, having CAS No. 61276-17-3) and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495- 60-3), and mixtures thereof.

[0192] Preferably, said composition comprises turmeric extract and cinnamaldehyde, and thymol, turmeric extract and cinnamon oil and thymol and cinnamaldehyde, turmeric extract and carvacrol and cinnamon oil and thymol, or turmeric extract and cinnamon oil and thymol and vanillin, or turmeric extract and cinnamon oil and thymol and menthol, or turmeric extract and cinnamon oil and thymol and linalool (C10H18C, such as e.g., preferably, having CAS No. 78-70-6), or turmeric extract and cinnamon oil and thymol and terpineol (C10H18C, such as e.g., preferably, having CAS No. 98-55-5), or turmeric extract and cinnamon oil and thymol and anthocyanins, or turmeric extract and cinnamon oil and thymol and catechins, or turmeric extract and cinnamon oil and thymol and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495-60-3) and mixtures thereof; or turmeric extract, thymol and cinnamon oil and capsaicin, or turmeric extract, thymol and cinnamon oil and thymol cinnamaldehyde, or turmeric extract, apigenin and cinnamon oil and thymol and eugenol.

[0193] Preferably, the mixture M present in the composition according to the invention can comprise, in addition or as an alternative to one or more ingredients selected in group (I), one or more compounds commonly used in the treatment of joint pathologies, selected from group (II) comprising or, alternatively, consisting of: glucosamine sulphate, chondroitin sulphate, methylsulfonylmethane (MSM), hyaluronic acid, hydrolysed collagen, type II collagen, and mixtures thereof; preferably glucosamine sulphate, chondroitin sulphate, MSM and mixtures thereof. Preferably, the mixture M present in the composition according to the invention can comprise, in addition or as an alternative to one or more Ingredients selected in group (I) and / or (II), a further second active ingredient selected in group (III) consisting of:

[0194] - bacterial strains or probiotic bacterial strains belonging to the genus Lactobacillus, Streptococcus, Leuconostoc, Bifidobacterium, Pediococcus, Enterococcus, Saccharomyces',

[0195] - prebiotics, such as e.g. inulin, lactulose, lactitol, mannooligosaccharides, fructooligosaccharides and galactooligosaccharides, tributyrin, monobutyrin (C7H14O4, such as e.g., preferably, having CAS No. 557-25-5), monolaurin (C15H30O4, such as e.g., preferably, having CAS No. 27215-38-9) and mixtures thereof;

[0196] - salts of metals, such as zinc and copper and / or mixtures thereof;

[0197] - organic acids, salts thereof and / or mixtures thereof;

[0198] - essential fatty acids and Omega-3, such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), derivatives from fish oil or other sources and / or mixtures thereof;

[0199] - vitamins, such as e.g. vitamin D, vitamin C, vitamin and, B group vitamins (e.g. B6, B12), vitamin K and / or mixtures thereof.

[0200] As described above, said composition further comprises a controlled-release lipid matrix that embeds or encloses said mixture M which comprises or, alternatively, consists of turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol, and, optionally, one or more of the further ingredients selected from group (I) and / or (II) and / or (III), wherein said controlled-release lipid matrix comprises or, alternatively, consists of at least one saturated or unsaturated, free or esterified fatty acid having a number of carbon atoms comprised in the C10-C30 range, and / or at least one triglyceride having saturated or unsaturated fatty acid chains having a number of carbon atoms comprised in the C6-C30 range, and / or at least one wax having a number of carbon atoms comprised in the C16-C36 range.

[0201] Preferably, said controlled-release lipid matrix comprises or, alternatively, consists of at least one hydrogenated fatty acid of plant origin having a number of carbon atoms comprised in the C14-C24 range and / or at least one hydrogenated triglyceride of plant origin having a number of carbon atoms comprised in the C14-C24 range and / or at least one wax of animal origin having a number of carbon atoms comprised in the C24-C36 range; preferably, wherein said fatty acid, triglyceride or wax is selected from: palm oil, sunflower oil, maize oil, rapeseed oil, peanut oil, soybean oil, olive oil, beeswax, and mixtures thereof.

[0202] The composition of the invention has the above-described features.

[0203] Embodiments FRn of the present invention are set forth below.

[0204] FR1 . A composition for use in a method of treatment, preventive and / or curative, of at least one joint pathology of an inflammatory and / or degenerative nature and / or of a symptom associated therewith by modulation of the receptors and / or enzymes of the endocannabinoid system, in a human being, or in a monogastric animal wherein said composition comprises:

[0205] - a mixture M comprising or, alternatively, consisting of a turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol and,

[0206] - optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient.

[0207] FR2. The composition for use according to FR1 , wherein said mixture M comprises or, alternatively, consists of a turmeric extract and cinnamon oil.

[0208] FR3. The composition for use according to FR1 , wherein said mixture M comprises or, alternatively, consists of a turmeric extract and thymol.

[0209] FR4. The composition for use according to FR1 , wherein said mixture M comprises or, alternatively, consists of turmeric extract, cinnamon oil and thymol.

[0210] FR5. The composition for use according to any one of FR 1-4, wherein said turmeric extract comprises curcumin and, optionally, other bioactive compounds such as demethoxycurcumin and bisdemethoxycurcumin, wherein said curcumin and said demethoxycurcumin and bisdemethoxycurcumin, optionally present, can be present in a phytocomplex.

[0211] FR6. The composition for use according to any one of FR 1-5, wherein said turmeric extract is in the form of an oleoresin, standardised extract, powder, or other extraction forms containing curcumin and / or curcuminoids; it is preferably in the form of an oleoresin.

[0212] FR7. The composition for use according to any one of FR 1-6, wherein said thymol is obtained from thyme extract or thyme essential oil or is a chemically synthesised molecule.

[0213] FR8. The composition for use according to any one of FR 1-7, wherein said mixture M further comprises at least a further first active compound, preferably deriving from a phytocompound (botanicals), selected in group (I) comprising or, alternatively, consisting of: boswellic acid, rosmarinic acid, harpagoside, alpha-pinene (C10H16, such as e.g., preferably, having CAS No. 80-56-8), alpha-thujone (C10H16O, such as e.g., preferably, having CAS No. 546-80-5), anethole (C10H12C, such as e.g., preferably, having CAS No. 104-46-1), anthocyanins, apigenin (C15H10C5, such as e.g., preferably, having CAS No. 520-36-5), beta-caryophyllene (C15H24, such as e.g., preferably, having CAS No. 87-44-5), camphor (C10H16C, such as e.g., preferably, having CAS No. 76-22-2), capsaicin (C18H27NO3, such as e.g., preferably, having CAS No. 404-86-4), carvacrol (C10H14C, such as e.g., preferably, having CAS No. 499-75-2), catechins, diallyl disulfide (C6H10S2, such as e.g., preferably, having CAS No. 2179-57-9), eugenol (C1 OH 1202, such as e.g., preferably, having CAS No. 97-53-0), 6-gingerol (C17H26O4, such as e.g., preferably, having CAS No. 23513-14-6), gamma-terpinene (C10H16, such as e.g., preferably, having CAS No. 99-85-4), linalool (C10H18C, such as e.g., preferably, having CAS No. 78-70-6), limonene (C10H16, such as e.g., preferably, having CAS No. 138-86-3), menthol (C10H20C, such as e.g., preferably, having CAS No. 89- 78-1), p-cymene (C10H14, such as e.g., preferably, having CAS No. 99-87-6), polyphenols, tannins, terpineol (C10H18C, such as e.g., preferably, having CAS No. 98-55-5), thymol (C10H14C, CAS No. 89-83-8), vanillin (C8H8O3, such as e.g., preferably, having CAS No. 121-33-5), verbascoside (C29H36O15, such as e.g., preferably, having CAS No. 61276-17-3) and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495- 60-3), and mixtures thereof.

[0214] FR9. The composition for use according to any one of FR 1-8, wherein said composition comprises turmeric extract and cinnamaldehyde, turmeric extract and thymol, turmeric extract and cinnamaldehyde and thymol, turmeric extract and carvacrol, or turmeric extract and vanillin, or turmeric extract and menthol, or turmeric extract and linalool (C10H18O, such as e.g., preferably, having CAS No. 78-70-6), or turmeric extract and terpineol (C10H18O, such as e.g., preferably, having CAS No. 98-55-5), or turmeric extract and anthocyanins, or turmeric extract and catechins, or turmeric extract and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495-60-3) and mixtures thereof; or turmeric extract, thymol and capsaicin, or turmeric extract, thymol and cinnamaldehyde, or turmeric extract, apigenin and eugenol.

[0215] FR10. The composition for use according to any one of FR 1-9, wherein the mixture M contained in said composition comprises, in addition to cinnamon oil and / or thymol and, optionally, said further first active compound (botanicals) selected in group (I), one or more compounds commonly used in the treatment of joint pathologies, selected from group (II) comprising or, alternatively, consisting of: glucosamine sulphate, chondroitin sulphate, methylsulfonylmethane (MSM), hyaluronic acid, hydrolysed collagen, type II collagen, and mixtures thereof; preferably glucosamine sulphate, chondroitin sulphate, MSM and mixtures thereof.

[0216] FR11 . The composition for use according to any one of FR 1-10, wherein said mixture M further comprises at least a further second active ingredient selected in group (III) consisting of:

[0217] - bacterial strains or probiotic bacterial strains belonging to the genus Lactobacillus, Streptococcus, Leuconostoc, Bifidobacterium, Pediococcus, Enterococcus, Saccharomyces',

[0218] - prebiotics, such as e.g. inulin, lactulose, lactitol, mannooligosaccharides, fructooligosaccharides and galactooligosaccharides, tributyrin, monobutyrin (C7H14O4, such as e.g., preferably, having CAS No. 557-25-5), monolaurin (C15H30O4, such as e.g., preferably, having CAS No. 27215-38-9) and mixtures thereof;

[0219] - salts of metals, such as zinc and copper and / or mixtures thereof;

[0220] - organic acids, salts thereof and / or mixtures thereof;

[0221] - essential fatty acids and Omega-3, such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), derivatives from fish oil or other sources and / or mixtures thereof;

[0222] - vitamins, such as e.g. vitamin D, vitamin C, vitamin and, B group vitamins (e.g. B6, B12), vitamin K and / or mixtures thereof.

[0223] FR12. The composition for use according to any one of FR 1-11 , wherein said composition further comprises a controlled-release lipid matrix that embeds or encloses said mixture M which comprises or, alternatively, consists of turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol, and, optionally, one or more of the further ingredients selected from group (I) and / or (II) and / or (III), wherein said controlled-release lipid matrix comprises or, alternatively, consists of at least one saturated or unsaturated, free or esterified fatty acid having a number of carbon atoms comprised in the C10-C30 range, and / or at least one triglyceride having saturated or unsaturated fatty acid chains having a number of carbon atoms comprised in the C6-C30 range, and / or at least one wax having a number of carbon atoms comprised in the CISCSS range;

[0224] FR13. The composition for use according to FR12, wherein said controlled-release lipid matrix comprises or, alternatively, consists of at least one hydrogenated fatty acid of plant origin having a number of carbon atoms comprised in the C14-C24 range and / or at least one hydrogenated triglyceride of plant origin having a number of carbon atoms comprised in the C14-C24 range and / or at least one wax of animal origin having a number of carbon atoms comprised in the C24-C36 range; preferably wherein said fatty acid, triglyceride or wax is selected from: palm oil, sunflower oil, maize oil, rapeseed oil, peanut oil, soybean oil, olive oil, beeswax, and mixtures thereof.

[0225] FR14. The composition for use according to any one of FR 1-13, wherein said composition is for use in a human being or a monogastric mammal, such as in dogs; preferably said composition is a feed, a feed additive or a dietary supplement for human beings or monogastric animals, preferably for monogastric mammals such as dogs.

[0226] FR15. The composition for use according to any one of FR 1-14, wherein said at least one pathology and / or symptom associated therewith is selected in the group that comprises or, alternatively, consists of: osteoarthritis, rheumatoid arthritis, psoriatic arthritis, septic arthritis of a non-bacterial nature, gouty arthritis, reactive arthritis, cervical and lumbar arthrosis, synovitis, tendinitis, tenosynovitis, bursitis, ankylosing spondylitis, inflammatory spondyloarthropathies, polyarthritis, systemic lupus erythematosus with joint manifestations, fibromyalgia with musculoskeletal and joint symptoms, arthralgia (joint pain), adhesive capsulitis (frozen shoulder), condensing osteitis, avascular osteonecrosis, spondylolisthesis, joint overload syndrome, patellofemoral syndrome, enthesitis (inflammation of tendon insertion sites), Sjogren's syndrome with joint involvement, carpal tunnel syndrome secondary to joint inflammation, plantar fasciitis, acute and chronic joint pain, joint and muscle stiffness, joint swelling and inflammation, functional limitation of joint mobility, and muscle fatigue and weakness correlated with joint pain; said pathology is preferably osteoarthritis.

[0227] FR16. A process for preparing the compositions according to any one of FR 12-15, wherein said process comprises a step in which oil-in-water emulsions and, separately, water-in-oil emulsions are prepared, said emulsions containing the ingredients of group (I) and / or group (II) and / or group (III) which constitute the mixture for yielding a composition in solid form.

[0228] Embodiments En of the present invention are set forth below.

[0229] E1 . A composition comprising:

[0230] - a mixture M comprising or, alternatively, consisting of a turmeric extract, cinnamon oil and thymol and,

[0231] - optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient.

[0232] E2. The composition according to E1 , wherein said turmeric extract comprises curcumin and, optionally, other bioactive compounds such as demethoxycurcumin and bisdemethoxycurcumin, wherein said curcumin and said demethoxycurcumin and bisdemethoxycurcumin, optionally present, can be present in a phytocomplex.

[0233] E3. The composition according to E1 or E2, wherein said turmeric extract is in the form of an oleoresin, standardised extract, powder, or other extraction forms containing curcumin and / or curcuminoids; it is preferably in the form of an oleoresin.

[0234] E4. The composition according to any one of E 1-3, wherein said thymol is obtained from thyme extract or thyme essential oil or is a chemically synthesised molecule.

[0235] E5. The composition according to any one of E 1-4, wherein said mixture M further comprises at least a further first active compound, preferably deriving from a phytocompound (botanicals), selected in group (I) comprising or, alternatively, consisting of: boswellic acid, rosmarinic acid, harpagoside, alpha-pinene (C10H16, such as e.g., preferably, having CAS No. 80-56-8), alpha-thujone (C10H16O, such as e.g., preferably, having CAS No. 546-80- 5), anethole (C10H12C, such as e.g., preferably, having CAS No. 104-46-1), anthocyanins, apigenin (C15H10C5, such as e.g., preferably, having CAS No. 520-36-5), beta-caryophyllene (C15H24, such as e.g., preferably, having CAS No. 87-44-5), camphor (C10H16C, such as e.g., preferably, having CAS No. 76-22-2), capsaicin (C18H27NO3, such as e.g., preferably, having CAS No. 404-86-4), carvacrol (C10H14C, such as e.g., preferably, having CAS No. 499-75-2), catechins, diallyl disulfide (C6H10S2, such as e.g., preferably, having CAS No. 2179- 57-9), eugenol (C10H12C2, such as e.g., preferably, having CAS No. 97-53-0), 6-gingerol (C17H26O4, such as e.g., preferably, having CAS No. 23513-14-6), gamma-terpinene (C10H16, such as e.g., preferably, having CAS No. 99-85-4), linalool (C10H18C, such as e.g., preferably, having CAS No. 78-70-6), limonene (C10H16, such as e.g., preferably, having CAS No. 138-86-3), menthol (C10H20C, such as e.g., preferably, having CAS No. 89-78- 1), p-cymene (C10H14, such as e.g., preferably, having CAS No. 99-87-6), polyphenols, tannins, terpineol (C10H18C, such as e.g., preferably, having CAS No. 98-55-5), thymol (C10H14C, CAS No. 89-83-8), vanillin (C8H8O3, such as e.g., preferably, having CAS No. 121-33-5), verbascoside (C29H36O15, such as e.g., preferably, having CAS No. 61276-17-3) and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495- 60-3), and mixtures thereof.

[0236] E6. The composition according to any one of E 1-5, wherein said composition comprises turmeric extract and cinnamaldehyde, and thymol, turmeric extract and cinnamon oil and thymol and cinnamaldehyde, turmeric extract and carvacrol and cinnamon oil and thymol, or turmeric extract and cinnamon oil and thymol and vanillin, or turmeric extract and cinnamon oil and thymol and menthol, or turmeric extract and cinnamon oil and thymol and linalool (C10H18C, such as e.g., preferably, having CAS No. 78-70-6), or turmeric extract and cinnamon oil and thymol and terpineol (C10H18C, such as e.g., preferably, having CAS No. 98-55-5), or turmeric extract and cinnamon oil and thymol and anthocyanins, or turmeric extract and cinnamon oil and thymol and catechins, or turmeric extract and cinnamon oil and thymol and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495-60-3) and mixtures thereof; or turmeric extract, thymol and cinnamon oil and capsaicin, or turmeric extract, thymol and cinnamon oil and thymol cinnamaldehyde, or turmeric extract, apigenin and cinnamon oil and thymol and eugenol. E7. The composition according to any one of E 1-6, wherein the mixture M contained in said composition, in addition to cinnamon oil and thymol, and, optionally, said further first active compound (botanicals) selected in group (I), comprises one or more compounds commonly used in the treatment of joint pathologies, selected from group (II) comprising or, alternatively, consisting of: glucosamine sulphate, chondroitin sulphate, methylsulfonylmethane (MSM), hyaluronic acid, hydrolysed collagen, type II collagen, and mixtures thereof; preferably glucosamine sulphate, chondroitin sulphate, MSM and mixtures thereof.

[0237] E8. The composition according to any one of E 1-7, wherein said mixture M further comprises at least a further second active ingredient selected in group (III) consisting of:

[0238] - bacterial strains or probiotic bacterial strains belonging to the genus Lactobacillus, Streptococcus, Leuconostoc, Bifidobacterium, Pediococcus, Enterococcus, Saccharomyces',

[0239] - prebiotics, such as e.g. inulin, lactulose, lactitol, mannooligosaccharides, fructooligosaccharides and galactooligosaccharides, tributyrin, monobutyrin (C7H14O4, such as e.g., preferably, having CAS No. 557-25-5), monolaurin (C15H30O4, such as e.g., preferably, having CAS No. 27215-38-9) and mixtures thereof;

[0240] - salts of metals, such as zinc and copper and / or mixtures thereof;

[0241] - organic acids, salts thereof and / or mixtures thereof;

[0242] - essential fatty acids and Omega-3, such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), derivatives from fish oil or other sources and / or mixtures thereof;

[0243] - vitamins, such as e.g. vitamin D, vitamin C, vitamin and, B group vitamins (e.g. B6, B12), vitamin K and / or mixtures thereof.

[0244] E9. The composition according to any one of E 1 -8, wherein said composition further comprises a controlled-release lipid matrix that embeds or encloses said mixture M which comprises or, alternatively, consists of turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol and, optionally, one or more of the further ingredients selected from group (I) and / or (II) and / or (III), wherein said controlled-release lipid matrix comprises or, alternatively, consists of at least one saturated or unsaturated, free or esterified fatty acid having a number of carbon atoms comprised in the C10-C30 range, and / or at least one triglyceride having saturated or unsaturated fatty acid chains having a number of carbon atoms comprised in the C6-C30 range, and / or at least one wax having a number of carbon atoms comprised in the C16-C36 range.

[0245] E10. The composition according to the E9, wherein said controlled-release lipid matrix comprises or, alternatively, consists of at least one hydrogenated fatty acid of plant origin having a number of carbon atoms comprised in the C14-C24 range and / or at least one hydrogenated triglyceride of plant origin having a number of carbon atoms comprised in the C14-C24 range and / or at least one wax of animal origin having a number of carbon atoms comprised in the C24-C36 range; preferably, wherein said fatty acid, triglyceride or wax is selected from: palm oil, sunflower oil, maize oil, rapeseed oil, peanut oil, soybean oil, olive oil, beeswax, and mixtures thereof.

[0246] E11. The composition according to any one of E 1-10, wherein said composition is preferably a feed or feed additive for animals, for example for dogs, and is formulated for oral use in solid form, e.g. granules, flakes, powder, soluble powder or granules, tablets, or capsules; or, alternatively, it is formulated in liquid form, e.g. selected from: solutions, suspensions, emulsions, liquid dispensable in spray form, or syrups; or, alternatively, in semiliquid form, e.g. selected from: softgel, or gel.

[0247] E12. A composition for use in a method of treatment, preventive and / or curative, of at least one joint pathology of an inflammatory and / or degenerative nature and / or of a symptom associated therewith by modulation of the receptors and / or enzymes of the endocannabinoid system, in a human being, or in a monogastric animal wherein said composition comprises:

[0248] - a mixture M comprising or, alternatively, consisting of a turmeric extract, cinnamon oil and thymol and,

[0249] - optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient.

[0250] E13. The composition for use according to E12, wherein said turmeric extract comprises curcumin and, optionally, other bioactive compounds such as demethoxycurcumin and bisdemethoxycurcumin, wherein said curcumin and said demethoxycurcumin and bisdemethoxycurcumin, optionally present, can be present in a phytocomplex.

[0251] E14. The composition for use according to E12 or E13, wherein said turmeric extract is in the form of an oleoresin, standardised extract, powder, or other extraction forms containing curcumin and / or curcuminoids; it is preferably in the form of an oleoresin.

[0252] E15. The composition for use according to any one of E 12-14, wherein said thymol is obtained from thyme extract or thyme essential oil or is a chemically synthesised molecule.

[0253] E16. The composition for use according to any one of E 12-15, wherein said mixture M further comprises at least a further first active compound, preferably deriving from a phytocompound (botanicals), selected in group (I) comprising or, alternatively, consisting of: boswellic acid, rosmarinic acid, harpagoside, alpha-pinene (C10H16, such as e.g., preferably, having CAS No. 80-56-8), alpha-thujone (C10H16O, such as e.g., preferably, having CAS No. 546-80-5), anethole (C10H12C, such as e.g., preferably, having CAS No. 104-46-1), anthocyanins, apigenin (C15H10C5, such as e.g., preferably, having CAS No. 520-36-5), beta-caryophyllene (C15H24, such as e.g., preferably, having CAS No. 87-44-5), camphor (C10H16C, such as e.g., preferably, having CAS No. 76-22-2), capsaicin (C18H27NO3, such as e.g., preferably, having CAS No. 404-86-4), carvacrol (C10H14C, such as e.g., preferably, having CAS No. 499-75-2), catechins, diallyl disulfide (C6H10S2, such as e.g., preferably, having CAS No. 2179-57-9), eugenol (C1 OH 1202, such as e.g., preferably, having CAS No. 97-53-0), 6-gingerol (C17H26O4, such as e.g., preferably, having CAS No. 23513-14-6), gamma-terpinene (C10H16, such as e.g., preferably, having CAS No. 99-85-4), linalool (C10H18C, such as e.g., preferably, having CAS No. 78-70-6), limonene (C10H16, such as e.g., preferably, having CAS No. 138-86-3), menthol (C10H20C, such as e.g., preferably, having CAS No. 89- 78-1), p-cymene (C10H14, such as e.g., preferably, having CAS No. 99-87-6), polyphenols, tannins, terpineol (C10H18C, such as e.g., preferably, having CAS No. 98-55-5), thymol (C10H14C, CAS No. 89-83-8), vanillin (C8H8O3, such as e.g., preferably, having CAS No. 121-33-5), verbascoside (C29H36O15, such as e.g., preferably, having CAS No. 61276-17-3) and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495- 60-3), and mixtures thereof.

[0254] E17. The composition for use according to any one of E 12-16, wherein said composition comprises turmeric extract and cinnamaldehyde, and thymol, turmeric extract and cinnamon oil and thymol and cinnamaldehyde, turmeric extract and carvacrol and cinnamon oil and thymol, or turmeric extract and cinnamon oil and thymol and vanillin, or turmeric extract and cinnamon oil and thymol and menthol, or turmeric extract and cinnamon oil and thymol and linalool (C10H18C, such as e.g., preferably, having CAS No. 78-70-6), or turmeric extract and cinnamon oil and thymol and terpineol (C10H18C, such as e.g., preferably, having CAS No. 98-55-5), or turmeric extract and cinnamon oil and thymol and anthocyanins, or turmeric extract and cinnamon oil and thymol and catechins, or turmeric extract and cinnamon oil and thymol and zingiberene (C15H24, such as e.g., preferably, having CAS No. 495-60-3) and mixtures thereof; or turmeric extract, thymol and cinnamon oil and capsaicin, or turmeric extract, thymol and cinnamon oil and thymol cinnamaldehyde, or turmeric extract, apigenin and cinnamon oil and thymol and eugenol.

[0255] E18. The composition for use according to any one of E 12-17, wherein the mixture M contained in said composition comprises, in addition to cinnamon oil and thymol and turmeric extract and, optionally, said further first active compound (botanicals) selected in group (I), one or more compounds commonly used in the treatment of joint pathologies, selected from group (II) comprising or, alternatively, consisting of: glucosamine sulphate, chondroitin sulphate, methylsulfonylmethane (MSM), hyaluronic acid, hydrolysed collagen, type II collagen, and mixtures thereof; preferably glucosamine sulphate, chondroitin sulphate, MSM and mixtures thereof.

[0256] E19. The composition for use according to any one of E 12-18, wherein said mixture M further comprises at least a further second active ingredient selected in group (III) consisting of:

[0257] - bacterial strains or probiotic bacterial strains belonging to the genus Lactobacillus, Streptococcus, Leuconostoc, Bifidobacterium, Pediococcus, Enterococcus, Saccharomyces',

[0258] - prebiotics, such as e.g. inulin, lactulose, lactitol, mannooligosaccharides, fructooligosaccharides and galactooligosaccharides, tributyrin, monobutyrin (C7H14O4, such as e.g., preferably, having CAS No. 557-25-5), monolaurin (C15H30O4, such as e.g., preferably, having CAS No. 27215-38-9) and mixtures thereof;

[0259] - salts of metals, such as zinc and copper and / or mixtures thereof;

[0260] - organic acids, salts thereof and / or mixtures thereof;

[0261] - essential fatty acids and Omega-3, such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), derivatives from fish oil or other sources and / or mixtures thereof;

[0262] - vitamins, such as e.g. vitamin D, vitamin C, vitamin and, B group vitamins (e.g. B6, B12), vitamin K and / or mixtures thereof.

[0263] E20. The composition for use according to any one of E 12-19, wherein said composition further comprises a controlled-release lipid matrix that embeds or encloses said mixture M which comprises or, alternatively, consists of turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol and, optionally, one or more of the further ingredients selected from group (I) and / or (II) and / or (III), wherein said controlled-release lipid matrix comprises or, alternatively, consists of at least one saturated or unsaturated, free or esterified fatty acid having a number of carbon atoms comprised in the C10-C30 range, and / or at least one triglyceride having saturated or unsaturated fatty acid chains having a number of carbon atoms comprised in the C6-C30 range, and / or at least one wax having a number of carbon atoms comprised in the CISCSS range.

[0264] E21. The composition for use according to the E20, wherein said controlled-release lipid matrix comprises or, alternatively, consists of at least one hydrogenated fatty acid of plant origin having a number of carbon atoms comprised in the C14-C24 range and / or at least one hydrogenated triglyceride of plant origin having a number of carbon atoms comprised in the C14-C24 range and / or at least one wax of animal origin having a number of carbon atoms comprised in the C24-C36 range; preferably, wherein said fatty acid, triglyceride or wax is selected from: palm oil, sunflower oil, maize oil, rapeseed oil, peanut oil, soybean oil, olive oil, beeswax, and mixtures thereof.

[0265] E22. The composition for use according to any one of E 12-21 , wherein said composition is for use in a human being or a monogastric mammal, such as in dogs; preferably said composition is a feed, a feed additive or a dietary supplement for human beings or monogastric animals, preferably for monogastric mammals such as dogs.

[0266] E23. The composition for use according to any one of E 12-22, wherein said at least one pathology and / or symptom associated therewith is selected in the group that comprises or, alternatively, consists of: osteoarthritis, rheumatoid arthritis, psoriatic arthritis, septic arthritis of a non-bacterial nature, gouty arthritis, reactive arthritis, cervical and lumbar arthrosis, synovitis, tendinitis, tenosynovitis, bursitis, ankylosing spondylitis, inflammatory spondyloarthropathies, polyarthritis, systemic lupus erythematosus with joint manifestations, fibromyalgia with musculoskeletal and joint symptoms, arthralgia (joint pain), adhesive capsulitis (frozen shoulder), condensing osteitis, avascular osteonecrosis, spondylolisthesis, joint overload syndrome, patellofemoral syndrome, enthesitis (inflammation of tendon insertion sites), Sjogren's syndrome with joint involvement, carpal tunnel syndrome secondary to joint inflammation, plantar fasciitis, acute and chronic joint pain, joint and muscle stiffness, joint swelling and inflammation, functional limitation of joint mobility, and muscle fatigue and weakness correlated with joint pain; said pathology is preferably osteoarthritis.

[0267] E24. A process for preparing the compositions according to any one of E 1-11 , wherein said process comprises a step in which oil-in-water emulsions and, separately, water-in-oil emulsions are prepared, said emulsions containing the ingredients of group (I) and / or group (II) and / or group (III) which constitute the mixture for yielding a composition in solid form.

[0268] EXPERIMENTAL SECTION

[0269] Example 1

[0270] The objective of this study was to investigate the effectiveness of a combination of turmeric oleoresin (CUR) and cinnamon essential oil (CAN) in reducing inflammation and the processes of degradation typical of osteoarthritis in an in vitro model. The study aimed to assess the potential synergistic effect of the combination on pro-inflammatory markers (e.g. IL-6 and MMP3) compared to the single treatments, using the Bliss independence model to confirm the synergism.

[0271] Furthermore, the action of the CAN+CUR combination on the endocannabinoid system (ECS) was studied by analysing the expression of key receptors such as CB2 and enzymes regulating the metabolism of endocannabinoids, such as DAGL-o and MAGL, in order to understand the molecular mechanisms underlying their beneficial effects.

[0272] Finally, the effect of adding thymol (TIM) to the CAN+CUR combination was assessed to determine any further improvements in the anti-inflammatory effectiveness.

[0273] MATERIALS AND METHODS Reagents

[0274] Unless otherwise specified, the chemical products and reagents for the cell cultures were purchased from Merck Life Science S.r.l. (Milan, Italy). The turmeric oleoresin (CUR) was purchased from Universal Oleoresins (Kerala, India).

[0275] CUR contained 29.40 ± 4.20% (w / w) of total curcuminoids, of which 18.20 ± 2.60% (w / w) was curcumin (CUR), 6.01 ± 0.85% (w / w) was demethoxycurcumin and 5.22 ± 0.74% (w / w) was bisdemethoxycurcumin.

[0276] The cinnamon essential oil (CAN) was purchased from Frey & Lau (Henstedt-Ulzburg, Germany). CAN contained 72.77% (w / w) of trans-cinnamaldehyde.

[0277] Thymol (TIM) was purchased from Merck Life Science S.r.l. (Milan, Italy) and had a purity > 98.5% (HPLC).

[0278] The stock solutions of CUR, CAN and TIM were prepared in 100% ethanol to concentrations that assured a final concentration of ethanol < 0.5% (v / v) in the cell culture medium.

[0279] Cell cultures

[0280] For the purpose of testing the activity of the single extracts and of the mixtures thereof, a human chondrosarcoma cell line (SW-1353 - Cat. HTB-94™), obtained from ATCC® (American Type Culture Collection - Manassas, Virginia), was used. The SW-1353 cells were maintained at 37 °C in an atmosphere containing 5% CO2, with a relative humidity of 95%. Between 20 and 30 passages were used to ensure a constant cell behaviour.

[0281] The basal medium was made up of high-glucose Dulbecco's Modified Eagle's Medium supplemented with 10% foetal bovine serum, 1 % L-glutamine, 100 U / mL of penicillin, 0.1 mg / mL of streptomycin and 1 % of non-essential amino acids. For all the analyses, the negative and positive control groups were incubated in a medium containing 0.5% (v / v) ethanol and / or 0.1 % (v / v) DMSO, to rule out any possible solvent-mediated effect.

[0282] Induction of the inflammatory state

[0283] The cells were seeded in 24-well plates at a density of 5 x 104cells / well and subjected to stimulation 48 hours after seeding. The cells were divided into five distinct groups (n=4): (1) negative control, (2) positive control, (3) group treated with CAN at 5 ppm, (4) group treated with CUR at 15 ppm, (5) group treated with the CAN + CUR mixture, respectively at 5 and 15 ppm.

[0284] The groups (4) and (5) were pretreated with the extracts for 2 hours. Subsequently, a stimulation was induced using a mixture of IL-1 p and TNF-o, both at 10 ng / mL for 24 hours, in the presence of the treatments. After 24 hours, the cells were rinsed with saline buffer, collected for RNA extraction and subjected to qPCR analysis.

[0285] The same protocol was used to analyse the synergism between the compounds, adding the following groups (n=4): (6) group treated with TIM at 5 ppm and (7) group treated with the mixture CAN + CUR + TIM, respectively at 5, 15 and 5 ppm.

[0286] Analysis of gene expression

[0287] The extraction of total RNA from the stimulated cells was carried out using the NucleoSpin RNA kit (Macherey- Nagel Inc., Bethlehem, USA), following the manufacturer's protocol. The RNA yield and quality were evaluated spectrophotometrical ly by measuring the absorbance at 260 and 280 nm with a Varioskan™ LUX (Thermo Fisher Scientific, Milan, Italy). Samples with a 260 / 280 ratio of less than 2.0 were excluded from the subsequent analyses. Subsequently, the RNA was subjected to reverse transcription using the IScript cDNA synthesis kit (Bio-Rad Laboratories, Hercules, California, USA) according to the manufacturer's instructions. For the qPCR reactions, duplicate assays were performed using the CFX Connect Real-Time PCR and iTaq Universal SYBR Green Supermix system (Bio-Rad Laboratories, Hercules, California, USA). The thermocycling protocol provided for an initial 3-minute denaturation step at 95 °C, following by 40 denaturation cycles at 95 °C for 10 seconds, and 30 seconds of annealing and extension at 60 °C. After amplification, an analysis of the melting curve was carried out for all the samples, with slow heating from 55 °C to 95 °C at a speed of 0.50 C / s to confirm the absence of nonspecific products.

[0288] The data on gene expression were normalised using two reference genes: the ribosomal protein L13 (RPL13) and the TATA-binding protein (TBP). The 2-MCTmethod [Livak KJ, et al., Methods 2001 ; 25:402-8] was used to calculate the variation in gene expression (fold changes), which is reported in the results as the variation relative to the negative control group.

[0289] The details regarding the primer sequences, the length of the expected product and the GenBank accession numbers are provided in Table 1. The primers were designed using the Primer-BLAST tool (https: / / www.ncbi.nlm.nih.gov / tools / primer-blast / ) and subsequently obtained from Merck Life Science S.r.l.

[0290] In Table 1 , the sequences are associated with their Sequence ID Number as stated in the sequence listing filed together with the present patent application (Sequence ID N. 1 - Sequence ID N. 20).

[0291] Table 1. bp: product length expressed in base pairs; F: forward; R: reverse

[0292] Assessment of the synergistic effect

[0293] In order to determine the synergism between the turmeric oleoresin (CUR) and cinnamon essential oil (CAN), the Bliss independence model [Lederer S, et al., Front. Pharmacol. 10: 1384] was applied; this is an approach commonly used to evaluate the interactions between combined treatments. The Bliss model makes it possible to assess whether the effect of two combined treatments exceeds the simple sum of their individual effects, thus indicating a synergism. This model presupposes that the individual effects of two treatments are independent, and the expected effect of the combination is calculated using the following formula:

[0294] Eexpected = Ea + Eb — (Ea * Eb)

[0295] Where Ea represents the percentage of reduction of the marker in the treatment with CAN compared to the positive control; Eb represents the percentage of reduction of the marker in the treatment with CUR compared to the positive control; Eexpected is the expected reduction, assuming independence between the two treatments.

[0296] Subsequently, the effect of the CAN+CUR combination as measured by qPCR (Eobserved) was compared with Eexpected. A synergistic effect occurs when the effect of the combination of two treatments exceeds the effect expected based on their individual effects, thus suggesting an enhanced interaction between the two compounds; therefore, if Eobserved > Eexpected, the combination is considered synergistic.

[0297] For this analysis, two key markers were selected: IL-6 and MMP3. The choice was based on their relevance both in inflammatory processes and in the degradation of the joint extracellular matrix, two central events in osteoarthritis. Finally, using the same method, an assessment was made of the synergistic effect of adding TIM to the CAN+CUR combination. The synergism was then assessed on the same markers by applying the same formula. In particular, Ea represents the effect of the CAN+CUR combination and Eb the effect of TIM.

[0298] Statistical analysis All the data are presented as the mean ± standard deviation (SD). The statistical analyses were carried out using GraphPad Prism version 10.2.3. The data distribution was evaluated by means of the Shapiro-Wilk test, with values of p greater than 0.05 indicating a normal distribution. The anomalous values were identified and excluded using the ROUT method, with a false discovery rate (Q) set at above 1 %.

[0299] Every measurement was made on distinct samples to ensure independent observations. In the qPCR experiments, the samples with a 260 / 280 ratio of less than 2.0 were excluded from the analysis to ensure the quality of the RNA. The datasets showed a normal distribution and were analysed using one-way ANOVA followed by Tukey's multiple comparison test. Statistical significance was set at p<0.05.

[0300] RESULTS

[0301] Anti-inflammatory effect

[0302] In order to assess the anti-inflammatory potential of the combination of turmeric oleoresin (CUR) and cinnamon essential oil (CAN), an analysis of the gene expression of pro-inflammatory markers (IL6, IL8, NFKB1, MMP1 , MMP3 and MMP13) was carried out in an in vitro model of osteoarthritis. The results of the qPCR analysis are shown in Figure 1.

[0303] The treatment with the CAN+CUR combination showed a significant reduction in the expression of the pro- inflammatory markers compared to the positive control (stimulated). In particular, the expression of IL-6 was reduced from 5539.72 in the positive control to 2987.39 with the combined CAN+CUR treatment (p<0.05, Fig. 1 A), a significantly lower value compared to the single treatments with CAN (3979.81) and CUR (4343.62).

[0304] As regards IL-8, the expression was reduced from 10935.88 in the positive control to 3437.92 with CAN+CUR (p<0.05, Fig. 1 B), differing significantly from the treatments with CAN (8924.13) and CUR (11012.30). In this case as well, the combined treatment was demonstrated to be more effective in suppressing the expression of the marker.

[0305] The treatment with CAN+CUR also significantly reduced the expression of NFKB1 , which decreased from 4.75 in the positive control to 1.55 (p<0.05, Fig. 1 C), a lower value compared to CAN (3.16) and CUR (2.94). This result further supports the role of the combination in modulating the activation of inflammatory pathways.

[0306] Furthermore, the treatment with CAN+CUR reduced the expression of the matrix metalloproteinases (MMPs), which are key enzymes in the degradation of joint cartilage. The expression of MMP1 was reduced from 31.55 in the positive control to 7.60 with the combined treatment (p<0.05, Fig. 1 D), a significantly more marked effect compared to the treatments with CAN (10.91) and CUR (19.38).

[0307] The expression of MMP3 was reduced from 26.95 in the positive control to 8.42 with CAN+CUR (p<0.05, Fig. 1 E), showing a greater efficacy compared to CAN (16.03) and CUR (25.12). Similarly, the expression of MMP13 was drastically reduced from 151.48 in the positive control to 0.69 with CAN+CUR (p<0.05, Fig. 1 F), a significantly stronger effect compared to CAN (12.98) and CUR (74.01).

[0308] These results suggest that the combination of CAN and CUR exerts a potent anti-inflammatory and anti- degenerative effect in the in vitro model of osteoarthritis, as it inhibits the expression of pro-inflammatory markers and metalloproteinases more effectively than the single treatments.

[0309] Endocannabinoid system (ECS)

[0310] In order to assess the effect of the combination of turmeric oleoresin (CUR) and cinnamon essential oil (CAN) on the endocannabinoid system (ECS), an analysis was conducted on the gene expression of the cannabinoid receptors CB1 and CB2 and the enzymes DAGL-o and MAGL in an in vitro model of osteoarthritis. The results of the qPCR analysis are shown in Figure 2.

[0311] The expression of the CB1 receptor increased from 0.63 in the positive control to 1 .44 with the combined CAN+CUR treatment (p<0.05, Fig. 2A), exceeding the levels observed with the single treatments, CAN (0.41) and CUR (0.50). This increase could reflect a compensatory effect or a complex modulation of the ECS as a result of the CAN+CUR combination, which could contribute to re-establishing the inflammatory homeostasis.

[0312] As regards the CB2 receptor, the treatment with CAN+CUR significantly increased the expression from 1 .32 in the positive control to 2.49 (p<0.05, Fig. 2B), with a larger increase compared to the single treatments with CAN (1.80) and CUR (1 .49). This result highlights a potential synergistic effect of the combination in activating the CB2 receptor, known for its protective and anti-inflammatory role.

[0313] The expression of the enzyme DAGL-o, involved in the synthesis of the endocannabinoid 2-AG, was reduced from 0.94 in the positive control to 0.51 with the combined CAN+CUR treatment (p<0.05, Fig. 2C). The single treatments with CAN (0.64) and CUR (0.64) also reduced the levels compared to the positive control, but the effect of the combined treatment was more pronounced. This regulation could indicate a greater efficiency in balancing the levels of 2-AG, thereby contributing to the modulation of inflammatory processes.

[0314] Finally, the expression of the enzyme MAGL, responsible for the degradation of 2-AG, was significantly reduced from 2.28 in the positive control to 0.66 with the combined CAN+CUR treatment (p<0.05, Fig. 2D). Although the single treatments with CAN (1.23) and CUR (1.44) showed inhibitory effects on the expression of MAGL, the combined treatment obtained the largest reduction, coming close to the levels observed in the negative control. The decrease in MAGL could favour a greater bioavailability of 2-AG, thus enhancing the CB2-mediated antiinflammatory effects.

[0315] These results suggest that the combination of CAN and CUR exerts a complex regulatory effect on the endocannabinoid system, by increasing the expression of the CB2 receptor and reducing the enzymes DAGL-o and MAGL, thus modulating the metabolism of the endocannabinoids.

[0316] Synergistic evaluation of the cinnamon oil, turmeric oleoresin and thymol combination

[0317] The analysis of the levels of gene expression of IL6 and MMP3 and comparison with the values expected according to the Bliss model are shown in Figure 3 and Figure 4.

[0318] As shown in Figure 3A, the combined CAN+CUR treatment significantly reduced the expression of IL6 compared to the single treatments. The expression decreased from 5539.72 in the positive control to 2987.39 (p<0.05), corresponding to a percentage reduction of 46.07% (Fig. 3B). This value exceeds the expected reduction calculated according to the Bliss model, equal to 43.67%, revealing a synergistic effect of the CAN+CUR combination.

[0319] Similarly, the combined CAN+CUR treatment led to a significant reduction in the levels of MMP3, which went from 26.95 in the positive control to 8.42 (p<0.05, Fig. 3C). The observed percentage reduction was 68.77%, greater than the reduction expected according to the Bliss model (44.58%, Fig. 3D). In this case as well, the results confirm the synergistic effect of the CAN+CUR combination in reducing the expression of MMP3.

[0320] Figure 4 shows the data related to the effect of adding thymol (TIM) to the CAN+CUR combination, with a comparison with the expected values calculated by means of the Bliss model. The combined CAN+CUR+TIM treatment further reduced the expression levels of IL6 rispetto compared both to the single treatments and to the CAN+CUR combination. The expression decreased from 5539.72 in the positive control to 2036.98 (p<0.05, Fig. 4A), with a percentage reduction of 63.23% (Fig. 4B). This value is greater than the expected reduction calculated according to the Bliss model (60.07%), thus indicating a synergistic effect of TIM with CAN+CUR.

[0321] As regards MMP3, the expression levels were reduced by the combined CAN+CUR+TIM treatment, though the difference was not statistically significant (Fig. 4C). However, when the percentage reduction was calculated and compared with the expected effect according to the Bliss model, a 73.93% reduction was observed, greater than the expected reduction of 65.71 % (Fig. 4D). This result suggests a synergistic effect of the CAN+CUR+TIM combination also in regulating the expression of MMP3.

[0322] Conclusions

[0323] The results of this study demonstrate that the combination of turmeric oleoresin (CUR) and cinnamon essential oil (CAN) exerts a synergistic effect in controlling the inflammatory and degenerative processes typical of osteoarthritis, in addition to a significant modulation of the endocannabinoid system (ECS).

[0324] The analysis of pro-inflammatory markers (IL-6, IL-8, NFKB1) and metalloproteinases (MMP1 , MMP3, MMP13) confirmed that the CAN+CUR combination significantly reduces the expression of these mediators compared to the single treatments. The addition of thymol (TIM) to the CAN+CUR combination further amplified the antiinflammatory effects, with an even more marked reduction in the levels of IL-6 and MMP3, thus highlighting a triple synergistic potential acting on inflammatory and degenerative processes.

[0325] The results obtained on the endocannabinoid system were equally relevant. The treatment with CAN+CUR brought about a significant increase in the expression of the CB2 receptor, known for its anti-inflammatory and protective properties, and a reduction in the expression of the enzymes DAGL-o and MAGL, while modulating the metabolism of endocannabinoids such as 2-AG. These effects suggest that the CAN+CUR combination could act not only by reducing inflammation, but also by favouring the protection and regeneration of the cartilage matrix through the regulation of the ECS.

[0326] Finally, the synergistic effect of the CAN+CUR combination, confirmed by the Bliss independence model for the key markers IL-6 and MMP3, suggests that the interaction between the two compounds significantly enhances the anti-inflammatory effectiveness. The modulation of the ECS represents a further molecular mechanism underlying the beneficial effects observed.

[0327] In conclusion, the combination of turmeric oleoresin (CUR) and cinnamon essential oil (CAN), with or without the addition of thymol (TIM), represents a promising therapeutic strategy for the treatment of osteoarthritis, thanks to the dual effect on the regulation of inflammatory processes and the modulation of the endocannabinoid system.

[0328] Example 2

[0329] The objective of this study was to investigate the effectiveness of a combination of turmeric oleoresin (CUR) and thymol (TIM) in reducing the inflammation and processes of degeneration typical of osteoarthritis in an in vitro model. The study aimed to assess the potential synergistic effect of the combination on pro-inflammatory markers (e.g. IL-6 and MMP3) compared to the single treatments, using the Bliss independence model to confirm the synergism.

[0330] Furthermore, the action of the CUR+TIM combination on the endocannabinoid system (ECS) was studied by analysing the expression of key receptors such as CB2 and enzymes regulating the metabolism of endocannabinoids, such as DAGL-o and MAGL, in order to understand the molecular mechanisms underlying their beneficial effects.

[0331] MATERIALS AND METHODS

[0332] Reagents

[0333] Unless otherwise specified, the chemical products and reagents for the cell cultures were purchased from Merck Life Science S.r.l. (Milan, Italy). The turmeric oleoresin (CUR) was purchased from Universal Oleoresins (Kerala, India).

[0334] CUR contained 29.40 ± 4.20% (w / w) of total curcuminoids, of which 18.20 ± 2.60% (w / w) was curcumin (CUR), 6.01 ± 0.85% (w / w) was demethoxycurcumin and 5.22 ± 0.74% (w / w) was bisdemethoxycurcumin.

[0335] Thymol (TIM) was purchased from Merck Life Science S.r.l. (Milan, Italy) and had a purity > 98.5% (HPLC).

[0336] The stock solutions of CUR and TIM were prepared in 100% ethanol to concentrations that assured a final concentration of ethanol < 0.5% (v / v) in the cell culture medium.

[0337] Cell cultures

[0338] For the purpose of testing the activity of the single extracts and of the mixtures thereof, a human chondrosarcoma cell line (SW-1353 - Cat. HTB-94™), obtained from ATCC® (American Type Culture Collection - Manassas, Virginia), was used. The SW-1353 cells were maintained at 37 °C in an atmosphere containing 5% CO2, with a relative humidity of 95%. Between 20 and 30 passages were used to ensure a constant cell behaviour.

[0339] The basal medium was made up of high-glucose Dulbecco's Modified Eagle's Medium supplemented with 10% foetal bovine serum, 1 % L-glutamine, 100 U / mL of penicillin, 0.1 mg / mL of streptomycin and 1 % of non-essential amino acids. For all the analyses, the negative and positive control groups were incubated in a medium containing 0.5% (v / v) ethanol and / or 0.1 % (v / v) DMSO, to rule out any possible solvent-mediated effect.

[0340] Induction of the inflammatory state The cells were seeded in 24-well plates at a density of 5 x 104cells / well and subjected to stimulation 48 hours after seeding. The cells were divided into five distinct groups (n=4): (1) negative control, (2) positive control, (3) group treated with CUR at 15 ppm, (4) group treated with TIM at 5 ppm, (5) group treated with the CUR + TIM mixture, respectively at 15 and 5 ppm. The groups (3), (4) and (5) were pretreated with the extracts for 2 hours. Subsequently, a stimulation was induced using a mixture of IL-113 and TNF-o, both at 10 ng / mL for 24 hours, in the presence of the treatments. After 24 hours, the cells were rinsed with saline buffer, collected for RNA extraction and subjected to qPCR analysis.

[0341] Analysis of gene expression The extraction of total RNA from the stimulated cells was carried out using the NucleoSpin RNA kit (Macherey- Nagel Inc., Bethlehem, USA), following the manufacturer's protocol. The RNA yield and quality were evaluated spectrophotometrically by measuring the absorbance at 260 and 280 nm with a Varioskan™ LUX (Thermo Fisher Scientific, Milan, Italy). Samples with a 260 / 280 ratio of less than 2.0 were excluded from the subsequent analyses. The details regarding the primer sequences, the length of the expected product and the GenBank accession numbers are provided in Table 2. The primers were designed using the Primer-BLAST tool (https: / / www.ncbi.nlm.nih.gov / tools / primer-blast / ) and subsequently obtained from Merck Life Science S.r.l.

[0342] In Table 2, the sequences are associated with their Sequence ID Number as stated in the sequence listing filed together with the present patent application (Sequence ID N. 1 - Sequence ID N. 20).

[0343] Table 2. bp: product length expressed in base pairs; F: forward; R: reverse

[0344] Subsequently, the RNA was subjected to reverse transcription using the iScript cDNA synthesis kit (Bio-Rad Laboratories, Hercules, California, USA) according to the manufacturer's instructions. For the qPCR reactions, duplicate assays were performed using the CFX Connect Real-Time PCR and iTaq Universal SYBR Green Supermix system (Bio-Rad Laboratories, Hercules, California, USA). The thermocycling protocol provided for an initial 3-minute denaturation step at 95 °C, following by 40 denaturation cycles at 95 °C for 10 seconds, and 30 seconds of annealing and extension at 60 °C. After amplification, an analysis of the melting curve was carried out for all the samples, with slow heating from 55 °C to 95 °C at a speed of 0.50 C / s to confirm the absence of nonspecific products.

[0345] The data on gene expression were normalised using two reference genes: the ribosomal protein L13 (RPL13) and the TATA-binding protein (TBP). The 2“MCTmethod [Livak KJ, et al., Methods 2001 ; 25:402-8] was used to calculate the variation in gene expression (fold changes), which is reported in the results as the variation relative to the negative control group.

[0346] The details regarding the primer sequences, the length of the expected product and the GenBank accession numbers are provided in Table 1. The primers were designed using the Primer-BLAST tool (https: / / www.ncbi.nlm.nih.gov / tools / primer-blast / ) and subsequently obtained from Merck Life Science S.r.l.

[0347] Assessment of the synergistic effect

[0348] In order to determine the synergism between the turmeric oleoresin (CUR) and thymol (TIM), the Bliss independence model [Lederer S, et al., Front. Pharmacol. 10:1384] was applied; this is an approach commonly used to evaluate the interactions between combined treatments. The Bliss model makes it possible to assess whether the effect of two combined treatments exceeds the simple sum of their individual effects, thus indicating a synergism. This model presupposes that the individual effects of two treatments are independent, and the expected effect of the combination is calculated using the following formula:

[0349] Eexpected = Ea + Eb — (Ea * Eb) Where Ea represents the percentage of reduction of the marker in the treatment with CAN compared to the positive control; Eb represents the percentage of reduction of the marker in the treatment with CUR compared to the positive control; Eexpected is the expected reduction, assuming independence between the two treatments.

[0350] Subsequently, the effect of the combination CUR+TIM as measured by qPCR {Eobserved was compared with Eexpected. A synergistic effect occurs when the effect of the combination of two treatments exceeds the one expected based on their individual effects, thus suggesting an enhanced interaction between the two compounds; therefore, if Eobserved > Eexpected, the combination is considered synergistic.

[0351] For this analysis, two key markers were selected: IL-6 and MMP3. The choice was based on their relevance both in inflammatory processes and in the degradation of the joint extracellular matrix, two central events in osteoarthritis.

[0352] Statistical analysis

[0353] All the data are presented as the mean ± standard deviation (SD). The statistical analyses were carried out using GraphPad Prism version 10.2.3. The data distribution was evaluated by means of the Shapiro-Wilk test, with values of p greater than 0.05 indicating a normal distribution. The anomalous values were identified and excluded using the ROUT method, with a false discovery rate (Q) set at above 1 %.

[0354] Every measurement was made on distinct samples to ensure independent observations. In the qPCR experiments, the samples with a 260 / 280 ratio of less than 2.0 were excluded from the analysis to ensure the quality of the RNA. The datasets showed a normal distribution and were analysed using one-way ANOVA followed by Tukey's multiple comparison test. Statistical significance was set at p<0.05.

[0355] RESULTS

[0356] Anti-inflammatory effect

[0357] In order to assess the anti-inflammatory potential of the combination of turmeric oleoresin (CUR) and thymol (TIM), an analysis of the gene expression of pro-inflammatory markers (IL6, IL8, NFKB1, MMP1 , MMP3 and MMP13) was carried out in an in vitro model of osteoarthritis. The results of the qPCR analysis are shown in Figure 5.

[0358] The treatment with the CUR+TIM combination showed a significant reduction in the expression of the pro- inflammatory markers compared to the positive control (stimulated). In particular, the expression of IL6 was reduced from 240.93 in the positive control to 120.32 with the combined CUR+TIM treatment (p<0.05, Fig. 5A), a significantly lower value compared to the single treatments with CUR (216.65 - p<0.05, Fig. 5A) and TIM (207.30 - p<0.05, Fig. 5A).

[0359] As regards IL8, the expression was reduced only numerically from 6278.80 in the positive control to 5557.19 with CUR+TIM (Fig. 5B), differing significantly from the treatments with CUR (5504.59 - p<0.05, Fig. 5B) and TIM (4757.53 - p<0.05, Fig. 5B). In this case, the combined treatment was not demonstrated to be effective in suppressing the expression of the marker.

[0360] The treatment with CUR+TIM also significantly reduced the expression of NFKB1 , which decreased from 3.17 in the positive control to 1.09 (p<0.05, Fig. 5C), a lower value compared to CUR (2.16 - p<0.05, Fig. 5C) and TIM (2.62 - p<0.05, Fig. 5C). This result further supports the role of the combination in modulating the activation of inflammatory pathways.

[0361] Furthermore, the treatment with CUR+TIM reduced the expression of the matrix metalloproteinases (MMPs), which are key enzymes in the degradation of joint cartilage. The expression of MMP1 was reduced from 6.88 in the positive control to 3.49 with the combined treatment (p<0.05, Fig. 5D), a significantly more marked effect compared to the treatments with CUR (5.74 - p<0.05, Fig. 5D) and TIM (6.51 - p<0.05, Fig. 5D).

[0362] The expression of MMP3 was reduced from 19.92 in the positive control to 5.58 with CUR+TIM (p<0.05, Fig. 5E), showing a greater efficacy compared to CUR (16.83 - p<0.05, Fig. 5E) and TIM (20.27 - p<0.05, Fig. 5E). Similarly, the expression of MMP13 was drastically reduced from 86.08 in the positive control to 11 .80 with CUR+TI M (p<0.05, Fig. 5F), a significantly stronger effect compared to CUR (32.28 - p<0.05, Fig. 5F) and TIM (99.35 - p<0.05, Fig. 5F).

[0363] These results suggest that the combination of CUR and TIM exerts a potent anti-inflammatory and anti- degenerative effect in the in vitro model of osteoarthritis, as it inhibits the expression of pro-inflammatory markers and metalloproteinases more effectively than the single treatments.

[0364] Endocannabinoid system (ECS)

[0365] In order to assess the effect of the combination of turmeric oleoresin (CUR) and thymol (TIM) on the endocannabinoid system (ECS), an analysis was conducted on the gene expression of the cannabinoid receptors CB1 and CB2 and the enzymes DAGL-o and MAGL in an in vitro model of osteoarthritis. The results of the qPCR analysis are shown in Figure 6.

[0366] The expression of the CB1 receptor was reduced numerically from 0.60 in the positive control to 0.41 with the combined CUR+TIM treatment (Fig. 6A), showing a similar effect compared to the single treatments with CUR (0.43 - Fig. 6A) and TIM (0.55 - Fig. 6A).

[0367] As regards the CB2 receptor, the treatment with CAN+CUR significantly increased the expression from 1 .25 in the positive control to 1.98 (p<0.05, Fig. 6B), exceeding the levels observed with the single treatments with CUR (1 .58 - Fig. 6B) and TIM (1.37 - Fig. 6B). This increase in the CB2 receptor, known for its anti-inflammatory properties, highlights the potential protective effect of the CUR+TIM combination.

[0368] The expression of the enzyme DAGL-o, involved in the synthesis of the endocannabinoid 2-AG, was reduced from 0.85 in the positive control to 0.60 with the combined CUR+TIM treatment (p<0.05, Fig. 6C), an effect comparable to the one observed with the single treatments with CUR (0.60 - Fig. 6C) and TIM (0.68 - Fig. 6C). This uniform reduction suggests an efficiency in modulating the levels of 2-AG which is independent of the combined treatment. Finally, the expression of the enzyme MAGL, responsible for the degradation of 2-AG, was significantly reduced from 1.38 in the positive control to 0.84 with the combined CUR+TIM treatment (p<0.05, Fig. 6D). Although the treatment with CUR (0.77 - Fig. 6D) showed a reduction similar to that of the combined treatment, the CUR+TIM combination nonetheless demonstrated a positive effect compared to TIM on its own (1.37 - p<0.05, Fig. 6D). The reduction in MAGL could contribute to improving the bioavailability of 2-AG, thereby supporting the CB2-mediated anti-inflammatory effects.

[0369] These results suggest that the combination of CUR and TIM exerts a regulatory effect on the endocannabinoid system, by increasing the expression of the CB2 receptor and modulating the enzymes DAGL-o and MAGL, with potential implications for the management of the inflammation associated with osteoarthritis.

[0370] Synergistic evaluation of the cinnamon oil, turmeric oleoresin and thymol combination

[0371] The analysis of the levels of gene expression of IL6 and MMP3 and comparison with the values expected according to the Bliss model are shown in Figure 7.

[0372] As shown in Figure 7A, the combined CUR+TIM treatment significantly reduced the expression of IL6 compared to the single treatments. The expression decreased from 240.93 in the positive control to 120.32 (p<0.05), corresponding to a percentage reduction of 50.06% (Fig. 7B). This value exceeds the expected reduction calculated according to the Bliss model, equal to 22.63% - indicated as a theoretical value - revealing a synergistic effect of the CUR+TIM combination in suppressing the expression of IL6.

[0373] Similarly, the combined CUR+TIM treatment led to a significant reduction in the levels of MMP3, which went from 19.92 in the positive control to 5.58 (p<0.05, Fig. 7C). The observed percentage reduction was 71.98%, greater than the reduction expected according to the Bliss model (15.49%, Fig. 7D). In this case as well, the results confirm the synergistic effect of the CUR+TIM combination in reducing the expression of MMP3.

[0374] These data suggest that the CUR+TIM combination exerts a potent synergistic effect in modulating the levels of expression of pro-inflammatory markers such as IL6 and MMP3, which exceeds the expected reductions calculated according to the Bliss model.

[0375] Conclusions

[0376] The results of this study demonstrate that the combination of turmeric oleoresin (CUR) and thymol (TIM) exerts a synergistic effect in controlling the inflammatory and degenerative processes typical of osteoarthritis, in addition to a significant modulation of the endocannabinoid system (ECS).

[0377] The analysis of pro-inflammatory markers (IL-6, IL-8, NFKB1) and metalloproteinases (MMP1 , MMP3, MMP13) confirmed that the CUR+TIM combination significantly reduces the expression of these mediators compared to the single treatments. In particular, the combination showed a marked reduction of IL-6 and MMP3, with values exceeding the reductions expected according to the Bliss model, thus highlighting a synergistic effect which acts more effectively on inflammatory and degenerative processes compared to the single treatments. However, in the case of IL-8, the combined treatment was not demonstrated to be more effective compared to the single compounds.

[0378] The results obtained on the endocannabinoid system were equally relevant. The treatment with CUR+TIM brought about a significant increase in the expression of the CB2 receptor, known for its anti-inflammatory and protective properties, and a reduction in the expression of the enzymes DAGL-o and MAGL, while modulating the metabolism of endocannabinoids such as 2-AG. Though the reduction in CB1 was not statistically significant compared to the single treatments, the increase in CB2 and enzymatic modulation suggest that the CUR+TIM combination could act by reducing inflammation and simultaneously promoting a protection of the cartilage matrix through the regulation of the ECS.

[0379] Finally, the synergistic effect of the CUR+TIM combination, confirmed by the Bliss independence model for the key markers IL-6 and MMP3, underscores that the interaction between the two compounds significantly enhances the anti-inflammatory effectiveness. The ability to modulate both the inflammatory markers and the ECS represents an important advance towards understanding the mechanisms of action of these substances.

[0380] In conclusion, the combination of turmeric oleoresin (CUR) and thymol (TIM) represents a promising therapeutic strategy for the treatment of osteoarthritis, thanks to the dual effect on the regulation of inflammatory processes and the modulation of the endocannabinoid system.

[0381] Example 3

[0382] The Applicant tested two different turmeric extracts in order to determine their anti-inflammatory effect in an in vitro model of osteoarthritis., using the same method as described in example 2.

[0383] For this analysis, two key markers were selected: IL-6 and MMP3. The choice was based on their relevance both in inflammatory processes and in the degradation of the joint extracellular matrix, two central events in osteoarthritis. In particular, an assessment was made of the effect of an oleoresin (CUR_A) and a turmeric extract with a 95% concentration of curcuminoids (about 70% curcumin), indicated as CUR_B.

[0384] The turmeric extract with which the study was conducted is an extract obtained from the roots of the plant Curcuma longa L, using water and ethanol (20:80) as solvents. The extract appears as a fine yellow powder with a particle size of 100% passing through an 80 mesh sieve and a concentration of curcuminoids equal to 95% (curcumin concentration > 70%), as measured by HPLC.

[0385] Said extract has a loss on drying < 1.0%, as measured according to Eur. Ph. <2.8.17>, a total ash content s 1.0%, as measured according to Eur. Ph. <2.4.16>, and a bulk density ranging from 30 to 60 g / 100 ml, as measured according to Eur. Ph. <2.9.34>.

[0386] The details regarding the primer sequences, the length of the expected product and the GenBank accession numbers are the same as indicated in Tables 1 and 2. The results of the qPCR analysis are shown in Figure 8.

Claims

AMENDED CLAIMS received by the International Bureau on 27 April 2026 (27.04.2026)1. A composition comprising:- a mixture M comprising or, alternatively, consisting of a turmeric extract, cinnamon oil and thymol and,- optionally, at least one acceptable pharmaceutical or food grade additive and / or excipient wherein said composition is for use in a method of treatment, preventive and / or curative, of at least one joint pathology of an inflammatory and / or degenerative nature and / or of a symptom associated therewith, in a monogastric animal.

2. The composition for use according to claim 1 , wherein said turmeric extract comprises curcumin and, optionally, other bioactive compounds preferably demethoxycurcumin and bisdemethoxycurcumin, wherein said curcumin and said demethoxycurcumin and bisdemethoxycurcumin, optionally present, may be present in a phytocomplex.

3. The composition for use according to claim 1 or 2, wherein said turmeric extract is in the form of an oleoresin, standardised extract, powder, or other extraction forms containing curcumin and / or curcuminoids; it is preferably in the form of an oleoresin.

4. The composition for use according to any one of claims 1-3, wherein said thymol is obtained from thyme extract or thyme essential oil or is a chemically synthesised molecule.

5. The composition for use according to any one of claims 1-4, wherein said mixture M further comprises at least a further first active compound, preferably deriving from a phytocompound (botanicals), selected in group (I) comprising or, alternatively, consisting of: boswellic acid, rosmarinic acid, harpagoside, alpha-pinene (C10H16, preferably, having CAS No. 80-56-8), alpha-thujone (C10H16O, preferably, having CAS No. 546-80-5), anethole (C10H12C, preferably, having CAS No. 104-46-1), anthocyanins, apigenin (C15H10C5, preferably, having CAS No. 520-36-5), beta-caryophyllene (C15H24, preferably, having CAS No. 87-44-5), camphor (C10H16C, preferably, having CAS No. 76-22-2), capsaicin (C18H27NO3, preferably, having CAS No. 404-86-4), carvacrol (C10H14C, preferably, having CAS No. 499-75-2), catechins, diallyl disulfide (C6H10S2, preferably, having CAS No. 2179-57- 9), eugenol (C10H12C2, preferably, having CAS No. 97-53-0), 6-gingerol (C17H26O4, preferably, having CAS No. 23513-14-6), gamma-terpinene (C10H16, preferably, having CAS No. 99-85-4), linalool (C10H18C, preferably, having CAS No. 78-70-6), limonene (C10H16, preferably, having CAS No. 138-86-3), menthol (C10H20C, preferably, having CAS No. 89-78-1), p-cymene (C10H14, preferably, having CAS No. 99-87-6), polyphenols, tannins, terpineol (C10H18C, preferably, having CAS No. 98-55-5), thymol (C10H14C, CAS No. 89-83-8), vanillin (C8H8O3, preferably, having CAS No. 121-33-5), verbascoside (C29H36O15, preferably, having CAS No. 61276- 17-3) and zingiberene (C15H24, preferably, having CAS No. 495-60-3), and mixtures thereof.

6. The composition for use according to any one of claims 1 -5, wherein said composition comprises turmeric extract and cinnamaldehyde, and thymol, turmeric extract and cinnamon oil and thymol and cinnamaldehyde, turmeric extract and carvacrol and cinnamon oil and thymol, or turmeric extract and cinnamon oil and thymol and vanillin, or turmeric extract and cinnamon oil and thymol and menthol, or turmeric extract and cinnamon oil and thymol and linalool (C10H18C, preferably, having CAS No. 78-70-6), or turmeric extract and cinnamon oil and thymol andterpineol (C10H18O, preferably, having CAS No. 98-55-5), or turmeric extract and cinnamon oil and thymol and anthocyanins, or turmeric extract and cinnamon oil and thymol and catechins, or turmeric extract and cinnamon oil and thymol and zingiberene (C15H24, preferably, having CAS No. 495-60-3) and mixtures thereof; or turmeric extract, thymol and cinnamon oil and capsaicin, or turmeric extract, thymol and cinnamon oil and thymol, cinnamaldehyde, or turmeric extract, apigenin and cinnamon oil and thymol and eugenol.

7. The composition for use according to any one of claims 1-6, wherein the mixture M contained in said composition, in addition to turmeric extract, cinnamon oil and thymol and, optionally, said further first active compound (botanicals) selected in group (I), comprises one or more compounds commonly used in the treatment of joint pathologies, selected from group (II) comprising or, alternatively, consisting of: glucosamine sulphate, chondroitin sulphate, methylsulfonylmethane (MSM), hyaluronic acid, hydrolysed collagen, type II collagen, and mixtures thereof; preferably glucosamine sulphate, chondroitin sulphate, MSM and mixtures thereof.

8. The composition for use according to any one of claims 1-7, wherein said mixture M further comprises at least a further second active ingredient selected in group (III) consisting of:- bacterial strains or probiotic bacterial strains belonging to the genus Lactobacillus, Streptococcus, Leuconostoc, Bifidobacterium, Pediococcus, Enterococcus, Saccharomyces',- prebiotics, preferably inulin, lactulose, lactitol, mannooligosaccharides, fructooligosaccharides and galactooligosaccharides, tributyrin, monobutyrin (C7H14O4, preferably, having CAS No. 557-25-5), monolaurin (C15H30O4, preferably, having CAS No. 27215-38-9) and mixtures thereof;- salts of metals, preferably zinc and copper and / or mixtures thereof;- organic acids, salts thereof and / or mixtures thereof;- essential fatty acids and Omega-3, preferably EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), derivatives from fish oil or other sources and / or mixtures thereof;- vitamins, preferably vitamin D, vitamin C, vitamin and, B group vitamins (preferably B6, B12), vitamin K and / or mixtures thereof.

9. The composition for use according to any one of claims 1-8, wherein said composition further comprises a controlled-release lipid matrix that embeds or encloses said mixture M which comprises or, alternatively, consists of turmeric extract and at least one compound selected from the group comprising or, alternatively, consisting of cinnamon oil and thymol and, optionally, one or more of the further ingredients selected from group (I) and / or (II) and / or (III), wherein said controlled-release lipid matrix comprises or, alternatively, consists of at least one saturated or unsaturated, free or esterified fatty acid having a number of carbon atoms comprised in the C10-C30 range, and / or at least one triglyceride having saturated or unsaturated fatty acid chains having a number of carbon atoms comprised in the C6-C30 range, and / or at least one wax having a number of carbon atoms comprised in the C16- C36 range.

10. The composition for use according to claim 9, wherein said controlled-release lipid matrix comprises or, alternatively, consists of at least one hydrogenated fatty acid of plant origin having a number of carbon atomscomprised in the C14-C24 range and / or at least one hydrogenated triglyceride of plant origin having a number of carbon atoms comprised in the C14-C24 range and / or at least one wax of animal origin having a number of carbon atoms comprised in the C24-C36 range; preferably, wherein said fatty acid, triglyceride or wax is selected from: palm oil, sunflower oil, maize oil, rapeseed oil, peanut oil, soybean oil, olive oil, beeswax, and mixtures thereof.11 . The composition for use according to any one of claims 1-10, wherein said composition is preferably a feed or feed additive for animals, for example for dogs, and is formulated for oral use in solid form, preferably granules, flakes, powder, soluble powder or granules, tablets, or capsules; or, alternatively, it is formulated in liquid form, preferably selected from: solutions, suspensions, emulsions, liquid dispensable in spray form, or syrups; or, alternatively, in semiliquid form, preferably selected from: softgel, or gel.

12. The composition for use according to any one of claims 1-11, wherein said composition is for use in a monogastric mammal, preferably in dogs; said composition is preferably a feed, a feed additive or a dietary supplement for human beings or monogastric animals, preferably for monogastric mammals preferably dogs.

13. The composition for use according to any one of claims 1-12, wherein said at least one pathology and / or symptom associated therewith is selected in the group that comprises or, alternatively, consists of: osteoarthritis, rheumatoid arthritis, psoriatic arthritis, septic arthritis of a non-bacterial nature, gouty arthritis, reactive arthritis, cervical and lumbar arthrosis, synovitis, tendinitis, tenosynovitis, bursitis, ankylosing spondylitis, inflammatory spondyloarthropathies, polyarthritis, systemic lupus erythematosus with joint manifestations, fibromyalgia with musculoskeletal and joint symptoms, arthralgia (joint pain), adhesive capsulitis (frozen shoulder), condensing osteitis, avascular osteonecrosis, spondylolisthesis, joint overload syndrome, patellofemoral syndrome, enthesitis (inflammation of tendon insertion sites), Sjogren's syndrome with joint involvement, carpal tunnel syndrome secondary to joint inflammation, plantar fasciitis, acute and chronic joint pain, joint and muscle stiffness, joint swelling and inflammation, functional limitation of joint mobility, and muscle fatigue and weakness correlated with joint pain; said pathology is preferably osteoarthritis.

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