A combination of propolis and probiotics to prevent and / or fight against chronic inflammatory bowel diseases (IBD).

Abstract

The present invention relates to a composition comprising propolis and at least one probiotic strain. More particularly, the invention aims to provide a new means of combating intestinal inflammation.

Description

Title of the invention: Combination of propolis and probiotics to prevent and / or combat chronic inflammatory bowel diseases (IBD). Technical field

[0001] The invention relates to the technical field of prevention and / or control of chronic inflammatory bowel diseases (IBD). In particular, the invention relates to a particular composition (a) combining propolis with at least one probiotic strain, its method of production and its uses. State of the art

[0002] Inflammatory bowel diseases, also known as IBD, are a group of complex and debilitating conditions that primarily include Crohn's disease and ulcerative colitis.

[0003] These conditions are characterized by inflammation of the wall of a part of the digestive tract, caused by deregulation of the intestinal immune system. This uncontrolled immune response is mediated by the release of proinflammatory molecules, consisting mainly of cytokines, which disrupt the permeability of the intestinal wall.

[0004] As a result, the natural barrier function of the intestinal wall is impaired, resulting in increased permeability. This impairment allows normally filtered pathogens to enter intestinal cells, causing inflammatory reactions in other organs.

[0005] This uncontrolled inflammation leads to tissue damage and a chronic course of the disease.

[0006] The origins of these conditions appear to result from a complex combination of environmental factors, patients' specific genetic susceptibility and particular reactivity of their immune system.

[0007] IBD causes often disabling symptoms, such as abdominal pain, frequent diarrhea, weight loss, and a significant impairment in quality of life. Patients with IBD face daily challenges and require ongoing medical management to control their intestinal inflammation and relieve their symptoms.

[0008] Current treatments for IBD are primarily aimed at reducing inflammation and relieving patients' symptoms. One of the most commonly used treatments is 5-aminosalicylate (5-ASA) in combination with an anti-TNF. However, these treatments have significant drawbacks. For example, anti-TNF drugs Inflammatory conditions can lead to unwanted side effects, such as gastric ulcers and an increased risk of infections.

[0009] Immunosuppressants, on the other hand, weaken the immune system, making patients more vulnerable to opportunistic infections. Biological therapies, although effective, are often expensive and require regular and sometimes invasive administrations, which can be a burden for patients. Furthermore, a proportion of patients with IBD do not respond to any existing treatment.

[0010] Faced with the limitations of existing treatments, it is essential to continue research to develop new therapeutic approaches for IBD, particularly based on natural treatments.

[0011] There is therefore a need for a new alternative treatment aimed at preventing and / or combating intestinal inflammation, more particularly preventing and / or combating chronic inflammatory bowel diseases, and, consequently, improving the quality of life of those suffering from these pathologies. Summary of the invention

[0012] To meet this need, the invention proposes a new composition (a) comprising propolis and at least one probiotic strain.

[0013] Propolis is a resinous, gummy and balsamic substance produced by bees. It is the result of the mixture between wax and salivary secretions of bees mixed with substances collected from the bark and buds of plants or trees, such as poplar, birch, willow, spruce and fir, baccharis or dalbergia.

[0014] Propolis is made up of a broad spectrum of polyphenols such as phenolic acids and flavonoids, giving it therapeutic properties, including antibacterial, antiviral, antifungal and anti-inflammatory properties.

[0015] A probiotic strain is a strain of live microorganism, usually a bacterium or yeast, that exhibits beneficial effects on the health of the host when consumed in adequate amounts. Probiotic strains are specific and identified by their precise taxonomic classification. They are carefully selected because of their particular characteristics, such as their ability to survive in the gastrointestinal tract, their adherence to epithelial cells, their resistance to gastric and bile acids, and their ability to modulate the composition and activity of the intestinal microbiota.

[0016] Probiotics work by colonizing the gastrointestinal tract, where they interact with the existing flora and with the epithelial cells of the intestine. They can exert various beneficial effects, such as competition with pathogenic microorganisms, stimulation of the immune system, production of beneficial metabolites, breakdown of dietary fiber and regulation of inflammation.

[0017] Surprisingly, the inventors discovered that the combination of propolis and at least one strain of probiotic made it possible to obtain an improved effect on the reduction of intestinal inflammation, thus making it possible to reduce the symptoms linked to IBD, preferentially to treat IBD.

[0018] Preferably, the composition (a) according to the invention comprises at least one propolis chosen from a poplar propolis, a baccharis propolis, a dalbergia propolis and their mixtures.

[0019] Preferably, the composition (a) according to the invention comprises propolis comprising at least 10% of total polyphenols relative to the weight of the propolis, even more preferably at least 15%.

[0020] Advantageously, the high concentration and diversity of polyphenols within propolis makes it possible to obtain an improved effect with at least one strain of probiotic on intestinal inflammation.

[0021] According to a preferred subject, the composition (a) according to the invention comprises at least one strain of probiotic chosen from Lactobacillus Paracasei, Lactobacillus Plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Bifidobacterium lactis, Bacillus subtilis and Enterococcus faecium.

[0022] Advantageously, these probiotic strains are individually already known to have an effect on reducing intestinal inflammation.

[0023] Preferably, the composition (a) according to the invention comprises at least 107 CFU / g of composition (a) of at least one probiotic strain.

[0024] According to another preferred object, the composition (a) according to the invention also comprises at least one prebiotic.

[0025] A prebiotic is a non-digestible substance found in certain foods, primarily dietary fiber, that promotes the growth and activity of beneficial bacteria in our digestive system, called probiotics. Unlike probiotics, which are live microorganisms, prebiotics are food substrates that selectively feed probiotics and help them grow.

[0026] When combined, probiotics and prebiotics work in tandem to enhance the beneficial effects on the gut microbiota. Prebiotics provide a preferential food source for probiotics, helping them survive and multiply in the gut. In turn, probiotics enhance their beneficial action through the stimulation provided by prebiotics.

[0027] According to another aspect, the invention relates to a process for preparing a composition (a) according to the invention comprising the implementation of the following steps: (a) Preparation of propolis; (b)Preparation of at least one probiotic strain; and (c) Mixture of propolis from step (a) and at least one probiotic strain selected in step (b).

[0028] Finally, according to a last aspect, the invention relates to the composition (a) according to the invention for its use as a food supplement or medical device in humans or animals.

[0029] Preferably, the composition (a) according to the invention can be used to prevent and / or combat intestinal inflammation, even more preferably to prevent and / or combat IBD.

[0030] Other characteristics and advantages will emerge from the detailed description of the invention, from the examples and from the figures which are solely illustrative and in no way limitative of the scope of the invention. Brief description of the drawings

[0031] [Fig.l] [Fig.l] is a graphical representation demonstrating the improved effect of composition (a) comprising the combination of propolis and at least one probiotic strain on the inhibition of TNF-alpha, a pro-inflammatory cytokine.

[0032] [Fig.2] [Fig.2] is a graphical representation demonstrating the improved effect of the composition (b) comprising the combination of artepillin C and at least one probiotic strain on the inhibition of TNF-alpha, a pro-inflammatory cytokine. Detailed description of the invention

[0033] Definitions:

[0034] For the purposes of the invention, the term "propolis" means a resinous, gummy and balsamic substance consisting of wax and salivary secretions from bees mixed with substances harvested from the bark and buds of plants or trees.

[0035] For the purposes of the invention, the term “raw propolis” means propolis obtained directly from the beehive without any prior treatment step.

[0036] By "propolis extract" within the meaning of the invention, we mean an extract comprising at least one set of molecules, the extract is obtained from any harvested propolis transformed by an extraction process making it possible to remove the impurities present in the raw extract and / or to concentrate the propolis into one or more of its constituents.

[0037] By "not containing alcohol" or "alcohol-free" within the meaning of the invention, it is meant that the composition (a) according to the invention contains a content of less than 0.1% alcohol. This alcohol content can be measured by techniques well known to those skilled in the art such as distillation, electronic densitometry or ebulliometry.

[0038] By "cold grinding" within the meaning of the invention, it is meant that the raw propolis has been exposed to a temperature below 0°C for a period of one hour before carrying out the grinding according to the invention.

[0039] By "systemic absorption" within the meaning of the invention, we mean the capacity of polyphenols to cross the enterocyte membrane and to be measured in the plasma.

[0040] By “aglycone form” within the meaning of the invention, it is meant that the polyphenols present in the extract are no longer linked to sugars and / or fatty acids.

[0041] By "gentle saponification" within the meaning of the invention, we mean a chemical hydrolysis carried out with a strong base concentration of between 0.01 and 0.1 M making it possible to concentrate the extract according to the invention in polyphenols in aglycone form without degrading them.

[0042] By “natural raw material” within the meaning of the invention, we mean a raw product found in nature.

[0043] By "fighting against" or "treating" within the meaning of the invention, we mean reducing the inflammatory state, that is to say a reduction in the progression of the inflammation, a stabilization, a reversal or regression, or even an interruption or inhibition of the progression of the inflammatory state.

[0044] By “synthetic origin” within the meaning of the invention, it is meant that the molecule is obtained by chemical synthesis.

[0045] For the purposes of the invention, the term “probiotic” means living microorganisms contributing to the balance of the intestinal flora.

[0046] For the purposes of the invention, the term “prebiotic” means a non-digestible substance which serves as a substrate for the intestinal microbiota.

[0047] For the purposes of the invention, the term “bulking agent” means a substance which increases the volume or mass of a composition without altering the properties or effectiveness of the other ingredients.

[0048] For the purposes of the invention, the term "anticaking agent" means a substance used to prevent the formation of lumps or agglomerates in powders, granules or mixtures. Its role is mainly to keep the particles separated and dispersed, thus ensuring a homogeneous distribution.

[0049] For the purposes of the invention, the term "intestinal inflammation" means an inflammatory reaction that occurs at the level of the intestinal mucosa. This is a condition characterized by an abnormal immune response of the body.

[0050] Composition (a)

[0051] To meet the need for a new treatment aimed at preventing and / or combating IBD, the inventors have developed a composition (a) comprising the combination of propolis and at least one strain of probiotic.

[0052] Advantageously, the composition (a) according to the invention makes it possible in particular to relieve and improve the quality of life of people suffering from IBD.

[0053] Thus, the invention relates to a composition (a) comprising propolis and at least one probiotic strain.

[0054] Advantageously, the combination of propolis and at least one strain of probiotic has an improved effect on the reduction of intestinal inflammation, in particular the reduction of the production of pro-inflammatory cytokines such as TNF-alpha.

[0055] According to one embodiment, the composition (a) according to the invention comprises propolis chosen from poplar propolis, baccharis propolis, dalbergia propolis and mixtures thereof.

[0056] Preferably, composition (a) according to the invention comprises Baccharis propolis.

[0057] Preferably, the composition (a) according to the invention comprises propolis comprising at least 10%, even more preferably at least 15% of total polyphenols (PPTX) relative to the total weight of the propolis.

[0058] Advantageously, the high content of total polyphenols helps to strengthen the antioxidant and anti-inflammatory effects of propolis. Indeed, the polyphenols present in propolis are known to have a powerful antioxidant effect. They neutralize free radicals, which are unstable molecules produced during inflammatory processes. By neutralizing free radicals, polyphenols help reduce oxidative stress and protect cells against damage caused by inflammation. Furthermore, the polyphenols in propolis have demonstrated anti-inflammatory effects. They are known to inhibit the production of certain enzymes and mediators of inflammation, including pro-inflammatory cytokines.

[0059] Preferably, the composition (a) according to the invention comprises propolis in raw form or in extract form.

[0060] When composition (a) according to the invention comprises baccharis propolis, said baccharis propolis is preferably in raw form.

[0061] According to a preferred embodiment, the composition (a) according to the invention comprises raw baccharis propolis in powder form.

[0062] When composition (a) according to the invention comprises baccharis propolis, said propolis comprises at least one molecule chosen from artepillin C, coumaric acid, Kaempferol, caffeic acid, drupanime and mixtures thereof.

[0063] Preferably, when composition (a) according to the invention comprises baccharis propolis, said propolis comprises artepillin C, coumaric acid, Kaempferol, caffeic acid and drupanime.

[0064] According to one embodiment, the composition (a) according to the invention comprises at least one strain of probiotic and baccharis propolis comprising artepillin C, preferably at least 5% of artepillin C by weight of the po- total lyphenols from propolis.

[0065] When composition (a) according to the invention comprises poplar propolis, said poplar propolis is preferably in the form of propolis extract.

[0066] According to one embodiment, when the composition (a) according to the invention comprises an extract of poplar propolis, said extract comprises at least one molecule chosen from apigenin, caffeic acid phenethyl ester, galangin, chrysin, pinocembrin and mixtures thereof.

[0067] Preferably, composition (a) comprises a poplar propolis extract comprising, by weight of total polyphenols of the extract: - at least 0.4% apigenin, preferably at least 0.6% - at least 2.6% CAPE, preferably at least 2.9% - at least 6.0% galangin, preferably at least 7% - at least 8.0% chrysin, preferably at least 8.5% and - at least 8.0% pinocembrin, preferably at least 9.2%.

[0068] According to another embodiment, the composition (a) according to the invention comprises at least one probiotic strain chosen from Lactobacillus Paracasei, Lactobacillus Plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Bifidobacterium lactis, Bacillus subtilis and Enterococcus faecium.

[0069] Preferably, the composition (a) according to the invention comprises at least 107 CFU / g of composition (a) of at least one probiotic strain, even more preferably at least 108 CFU / g, in particular at least 5*109 CFU / g.

[0070] The probiotic strain Lactobacillus paracasei, also known as L. paracasei, is a lactic acid bacterium belonging to the Lactobacillaceae family. It is part of the bacterial microbiota naturally present in the human digestive tract and can also be found in certain fermented food products such as yogurt.

[0071] L. paracasei has been widely studied due to its probiotic properties and potential beneficial effects on health, including intestinal inflammation. L. paracasei is known for its ability to survive and establish itself in the gastrointestinal tract, despite the acidic conditions of the stomach and digestive enzymes. This probiotic strain also has the ability to colonize the intestinal mucosa, allowing it to interact directly with intestinal epithelial cells.

[0072] Preferably, the composition (a) according to the invention comprises a strain of Lactobacillus Paracasei referenced LMG S-25516 from the BCCM (Belgian Co-ordinated Collections of Microorganism).

[0073] According to one embodiment, the composition (a) according to the invention comprises at least 107 CFU / g of composition (a) of the strain Lactobacillus Paracasei, preferably at least 108UFC / g, especially at least 2.5*109UFC / g.

[0074] The probiotic strain Lactobacillus plantarum, also known as L. plantarum, is a lactic acid bacterium widely used as a probiotic beneficial to human health. It belongs to the Lactobacillaceae family and can be found naturally in various environments, such as fruits, vegetables and fermented products.

[0075] L. plantarum is renowned for its hardiness and ability to survive harsh environmental conditions, including stomach acidity and digestive enzymes.

[0076] L. plantarum has many beneficial properties for the intestine, including its ability to modulate the reactions of the immune system, in particular by stimulating the production of certain anti-inflammatory cytokines. L. Plantarum is also known to reduce certain symptoms, including abdominal pain and bloating in patients with irritable bowel syndrome. In addition, L. plantarum can also strengthen the intestinal barrier by promoting the production of protective mucus and reducing the risk of intestinal permeability, which can help prevent inflammatory problems and imbalances in the intestinal flora.

[0077] Preferably, composition (a) according to the invention comprises a strain of Lactobacillus Plantarum referenced 1-5597 with the CNCM (National Collection of Cultures of Micro-Organisms).

[0078] According to one embodiment, the composition (a) according to the invention comprises at least 107 CFU / g of composition (a) of the strain Lactobacillus Plantarum, preferably at least 108 CFU / g, in particular at least 2.5*109 CFU / g.

[0079] Preferably, the composition (a) according to the invention comprises at least one probiotic strain chosen from a strain of Lactobacillus Plantarum referenced I-5597 (CNCM), a strain of Lactobacillus Paracasei referenced LMG S-25516 (BCCM) and their mixture.

[0080] According to a particular embodiment, the composition (a) according to the invention comprises propolis and a mixture consisting of at least two strains of probiotic.

[0081] According to one embodiment, composition (a) comprises a mixture of at least two strains of probiotics comprising: - between 40 and 60% by weight of the mixture of the Lactobacillus Paracasei strain, preferably of the LMG S-25516 (BCCM) strain; and - between 40 and 60% by weight of the mixture of the Lactobacillus Plantarum strain, preferably of the 1-5597 (CNCM) strain.

[0082] Preferably, composition (a) comprises a mixture of at least two probiotic strains comprising 50% by weight of the mixture of the strain Lactobacillus Paracasei and 50% by weight of the mixture of the strain Lactobacillus Plantarum.

[0083] According to another embodiment, the composition (a) according to the invention comprises: - at least 107 CFU / g of composition (a) of the strain Lactobacillus Paracasei, preferably of the strain LMG S-25516 (BCCM); and - at least 107 CFU / g of composition (a) of the Lactobacillus Plantarum strain, preferably of the 1-5597 (CNCM) strain.

[0084] Preferably, the composition (a) according to the invention comprises: - at least 2.5* 109 CFU / g of composition (a) of the strain Lactobacillus Paracasei, preferably of the strain LMG S-25516 (BCCM); and - at least 2.5* 109 CFU / g of composition (a) of the Lactobacillus Plantarum strain, preferably of the 1-5597 (CNCM) strain.

[0085] According to one embodiment, the composition (a) according to the invention comprises: - between 40 and 50% of propolis by weight of composition (a); - between 30 and 45% of probiotic strains by weight of composition (a).

[0086] According to one embodiment, the composition (a) according to the invention also comprises at least one prebiotic.

[0087] Advantageously, the use of prebiotics in composition (a) according to the invention reinforces the effect of the probiotics by guaranteeing them a source of energy.

[0088] Preferably, composition (a) comprises at least one prebiotic chosen from a bulking agent, an anti-caking agent and their mixture.

[0089] According to a particularly preferred embodiment, composition (a) comprises, as prebiotic, a plant fiber, preferably an acacia fiber and / or a carob fiber.

[0090] Preferably, the composition (a) according to the invention comprises: - between 40 and 50% of propolis by weight of composition (a); - between 15 and 30% of prebiotics by weight of composition (a); - between 30 and 45% of probiotics by weight of composition (a).

[0091] According to a particularly preferred embodiment, composition (a) comprises: - between 40 and 50% of Baccharis propolis, preferably in powder form, by weight of composition (a); - between 15 and 30% of acacia fibers by weight of composition (a); - between 30 and 45% of at least one probiotic chosen from a strain of Lactobacillus Paracasei, a strain of Lactobacillus Plantarum and their mixture by weight of composition (a).

[0092] According to another particularly preferred embodiment, composition (a) comprises: - between 40 and 50% of raw Baccharis propolis, preferably in the form of powder, by weight of composition (a); - between 15 and 30% of acacia fibers by weight of composition (a); - between 30 and 45% of a mixture of probiotics including: *between 40 and 60% by weight of the mixture of the Lactobacillus Paracasei strain, preferably of the LMG S-25516 (BCCM) strain; and *between 40 and 60% by weight of the mixture of the Lactobacillus Plantarum strain, preferably of the 1-5597 strain (CNCM).

[0093] According to one embodiment, the composition (a) according to the invention is in powder form, in particular in a gastro-resistant capsule which can be administered orally.

[0094] According to another embodiment, the composition (a) according to the invention is capable of being obtained by any method known to those skilled in the art. More particularly, the composition (a) according to the invention is capable of being obtained by a preparation method comprising the implementation of the following steps: (a) Preparation of propolis (b) Preparation of at least one probiotic strain (c) Mixture of at least one propolis selected in step (a) and at least one strain of prebiotic prepared in step (b).

[0095] When the propolis of step (a) is a poplar propolis extract, said poplar propolis extract is capable of being obtained by implementing the following steps: a) Grinding of at least one raw poplar propolis, b) Maceration of the propolis powder obtained in step a) in an extraction solvent, c) Filtration of the macerate obtained in step b) and recovery of the filtrate, d) Evaporation of the filtrate obtained in step c) forming a residue, e) Mixing the residue obtained in step d) with a mixture of organic solvent and aqueous solvent with stirring, f) Decantation of the mixture obtained in step e) and recovery of the organic phase, g) Washing of the organic phase obtained in step f) using anhydrous sodium sulfate salts, h) Filtration of the organic phase obtained in step g), i) Evaporation of the organic solvent

[0096] When the propolis of step (a) is a raw baccharis propolis, said propolis preparation is obtained by grinding, preferably by cold grinding.

[0097] According to one embodiment, step (a) of preparing the propolis comprises a step of mixing the propolis with at least one prebiotic, preferably at least one bulking agent, an anti-caking agent or their mixture.

[0098] Preferably, step (a) of preparing the propolis comprises a step of mixing the propolis with plant fiber, even more preferably acacia fiber and / or carob fiber.

[0099] Preferably, at least one probiotic strain from step (b) is chosen from Lactobacillus Paracasei, Lactobacillus Plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Bifidobacterium lactis, Bacillus subtilis and Enterococcus faecium.

[0100] According to one embodiment, step (b) consists of the preparation of a mixture consisting of at least two strains of propolis. Preferably, the mixture of step (b) consists of the strain Lactobacillus paracasei and the strain Lactobacillus Plantarum.

[0101] Even more preferably, the mixture of step (b) consists of the strain Lactobacillus paracasei LMG S-25516 (BCCM) and the strain Lactobacillus Plantarum 1-5597 (CNCM).

[0102] Process for obtaining composition fa):

[0103] According to another aspect, the invention relates to a method for preparing the composition (a) according to the invention, comprising the implementation of the following steps: (a) Preparation of propolis (b) Preparation of at least one strain of probiotic (c) Mixture of the propolis prepared in step (a), of at least one strain of probiotic prepared in step (b).

[0104] Preferably, the propolis of step (a) is chosen from poplar propolis, baccharis propolis, dalbergia propolis and mixtures thereof.

[0105] When the propolis of step (a) is a raw baccharis propolis, said preparation of the propolis is carried out by grinding the raw propolis, preferably by cold grinding.

[0106] According to one embodiment, when the propolis of step (a) is a raw baccharis propolis, said preparation of propolis is obtained by implementing the following steps: - grinding of raw baccharis propolis; and - Gradual incorporation of at least one prebiotic by cold mixing.

[0107] Advantageously, the baccharis propolis preparation from step (a) is a non-sticky powder.

[0108] Preferably, at least one prebiotic is chosen from a bulking agent, an anti-caking agent and their mixture.

[0109] According to a particularly preferred embodiment, the prebiotic of step (a) is a plant fiber, preferably an acacia fiber and / or a carob fiber.

[0110] When the propolis of step (a) is an extract of poplar propolis, said extract poplar propolis is obtained by implementing the following steps: a) Grinding of at least one raw poplar propolis, b) Maceration of the propolis powder obtained in step a) in an extraction solvent, c) Filtration of the macerate obtained in step b) and recovery of the filtrate, d) Evaporation of the filtrate obtained in step c) forming a residue, e) Mixing the residue obtained in step d) with a mixture of organic solvent and aqueous solvent with stirring, f) Decantation of the mixture obtained in step e) and recovery of the organic phase, g) Washing of the organic phase obtained in step f) using anhydrous sodium sulfate salts, h) Filtration of the organic phase obtained in step g), i) Evaporation of the organic solvent

[0111] Preferably, the raw poplar propolis used in step a) comprises at least 45% resin, preferably at least 55% resin, even more preferably at least 60% resin.

[0112] Advantageously, the resin concentration of the raw propolis is a reliable indicator of its quality; the higher the resin content of the raw propolis, the higher the concentration of active ingredients in the extract according to the invention will be.

[0113] The grinding of step a) can be carried out by crushing, percussion, abrasion or shearing. Preferably, the grinding of step a) is carried out by shearing.

[0114] According to a preferred embodiment, the grinding of step a) is carried out cold, that is to say at a temperature below 0°C.

[0115] In a particularly preferred embodiment, the particles constituting the ground material obtained in step a) have a diameter of between 0.1 and 1 mm, preferably between 0.2 and 0.6 mm.

[0116] Advantageously, the grinding step according to the invention greatly improves the concentration of polyphenols in said extract by increasing the exchange surface between the raw poplar propolis and the extraction solvent of step b).

[0117] In the context of the invention, the extraction solvent of step b) comprises an organic solvent, an aqueous solvent and a strong base. For the purposes of the invention, step b) is a saponification step, preferably a mild saponification.

[0118] Advantageously, the strong base will break the sugar-polyphenol bonds, thus making it possible to obtain a majority of polyphenols in aglycone form, making them easily assimilated by the intestinal mucosa.

[0119] The aglycone form of the polyphenols in poplar propolis extract allows the polyphenols to be directly assimilated by the mucosa without prior enzymatic treatment.

[0120] Preferably, the extraction solvent of step b) comprises a mixture of organic solvent / aqueous solvent and a strong base, the solvent / strong base ratio is between 1 / 10 and 1 / 4 by volume. The mixture of organic solvent / aqueous solvent of step b) preferably has a ratio of between 40 / 60 to 90 / 10 by volume, even more preferably a ratio of between 70 / 30 and 85 / 15 by volume.

[0121] The organic solvent present in the extraction solvent of step b) is preferably chosen from ethanol and methanol.

[0122] The aqueous solvent present in the extraction solvent of step b) may be water.

[0123] Preferably, the strong base of step b) is present at a concentration of between 0.01 and 0.1 M, preferably between 0.02 and 0.08 M, even more preferably at a concentration of 0.03 M.

[0124] Advantageously, a strong base concentration of between 0.01 and 0.1M makes it possible to concentrate the propolis extract in polyphenols in aglycone form without degrading them.

[0125] The strong base present in the extraction solvent of step b) is preferably chosen from potassium hydroxide and sodium hydroxide.

[0126] According to a particularly preferred embodiment, the extraction solvent of step b) is sodium hydroxide.

[0127] The extraction solvent of step b) is preferably chosen from a mixture of ethanol / water and sodium hydroxide or methanol / water and sodium hydroxide.

[0128] The maceration of step b) is carried out with continuous stirring, preferably using a vortex adapted to the volume of ground material, a paddle mixer or a sonication or ultrasound system.

[0129] The duration of the maceration of step b) can vary depending on the volume of ground material from step a) between 2 hours and 10 days.

[0130] The filtration of step c) can be carried out by successive filtration, centrifugal filtration or successive gravity decantation with filter filtration or plate filtration.

[0131] According to a preferred embodiment, the filtration of step c) comprises a successive centrifugal filtration with nylon filters ranging from 200 μm up to 5 μm.

[0132] Advantageously, the filtrate obtained in step c) is clear and without sediment.

[0133] The evaporation of step d) or i) can be carried out under vacuum at a pressure of between between 100 and 300mbar and at a temperature between 30 and 60°C.

[0134] The evaporation of step d) is preferably carried out under vacuum at a pressure of between 100 and 300 mbar and a temperature of between 30 and 60°C, again more preferably at a pressure of 140mbar and a temperature between 45 and 50°C.

[0135] In the context of the invention, evaporation must be rapid while adopting as low a temperature as possible in order to preserve the polyphenols of the propolis.

[0136] Advantageously, the evaporation of step d) makes it possible to obtain a residue with an alcohol content of less than 0.1%. The techniques for determining the alcohol content are well known to those skilled in the art. In the context of the invention, the content is determined by distillation and by electron densitometry or by ebulliometry.

[0137] Preferably, the mixing of step e) is carried out with stirring using a vortex adapted to the volume of residue or a paddle mixer.

[0138] In a particularly preferred embodiment of the invention, the mixing of step e) is carried out with stirring until the residue obtained in step d) is completely dissolved.

[0139] The organic solvent of step e) is preferentially chosen from ethyl acetate, methyl acetate and dimethyl ether and their mixtures.

[0140] The aqueous solvent of step e) may be water.

[0141] Preferably, the organic solvent / aqueous solvent mixture of step e) is a mixture of ethyl acetate / water.

[0142] The mixture of organic solvent / aqueous solvent of step e) preferably has a ratio of between 30 / 70 and 90 / 10 by volume, even more preferably a ratio of between 50 / 50 and 80 / 20 by volume.

[0143] In a particularly preferred embodiment of the invention, the organic solvent / aqueous solvent mixture of step e) is a mixture of ethyl acetate / water in a ratio of 50 / 50 by volume.

[0144] The residue / solvent ratio of the mixture from step e) is preferably between 1 / 3 and 1 / 4 (weight / volume).

[0145] The decantation of step f) can be carried out by gravity decantation or centrifugation.

[0146] Step g) of washing the organic phase using sodium sulfate salts advantageously makes it possible to trap the remaining water molecules in the organic phase.

[0147] Step h) of filtration of the organic phase obtained in step g) makes it possible to eliminate the salt crystals from the organic phase and thus to obtain an organic phase containing no water.

[0148] The filtration of step h) is carried out on a filter having meshes that are narrow enough to remove the salt crystals from the organic phase. A person skilled in the art is perfectly capable of choosing a filter having a mesh size adapted according to the size of the salt crystals. By way of non-limiting example, the Whatmann No. 4 paper or a coffee filter is sufficient to remove said crystals.

[0149] Preferably, said method for obtaining a propolis extract also comprises a step h') of selecting the molecules of interest.

[0150] The evaporation of step i) is preferably carried out under vacuum at a pressure of between 150 and 300 mbar and a temperature of between 30 and 60°C, even more preferably at a pressure of between 200 and 250 mbar and a temperature of between 40 and 45°C.

[0151] Preferably, at least one probiotic strain from step (b) is chosen from a strain of Lactobacillus Paracasei, a strain of Lactobacillus Plantarum and their mixture.

[0152] Preferably, the preparation of step (b) comprises at least one strain of probiotic chosen from a strain of Lactobacillus Plantarum referenced I-5597 (CNCM), a strain of Lactobacillus Paracasei referenced LMG S-25516 (BCCM) and their mixture.

[0153] According to one embodiment, step (b) consists of the preparation of a mixture comprising at least two strains of probiotic.

[0154] Preferably, the mixture of probiotics from step (b) comprises: - between 40 and 60% by weight of the mixture of the Lactobacillus Paracasei strain; and - between 40 and 60% by weight of the mixture of the Lactobacillus Plantarum strain.

[0155] According to a preferred embodiment, the mixture of probiotics of step (b) comprises a mixture of two strains of probiotics comprising: - 50% by weight of the mixture of the Lactobacillus Paracasei strain, preferably of the Lactobacillus paracasei strain LMG S-25516 (BCCM); and - 50% by weight of the mixture of the Lactobacillus Plantarum strain, preferably of the Lactobacillus Plantarum 1-5597 (CNCM) strain.

[0156] Preferably, the mixing of step (c) is carried out using a paddle mixer.

[0157] According to one embodiment, the mixture of step (c) comprises: - between 40 and 50% of propolis by weight of the mixture; - between 30 and 35% of probiotic strain by weight of the mixture.

[0158] According to another embodiment, the mixture of step (c) comprises: - between 40 and 50% of propolis by weight of the mixture; - between 15 and 30% of prebiotics by weight of the mixture; and - between 30 and 45% of probiotics by weight of the mixture.

[0159] According to a particularly preferred embodiment, the mixture of step (c) comprises: - between 40 and 50% of raw Baccharis propolis by weight of the mixture; - between 15 and 30% of acacia fibers by weight of the mixture; - between 30 and 45% of at least one probiotic chosen from a strain of Lactobacillus Paracasei and / or a strain of Lactobacillus Plantarum by weight of the mixture.

[0160] Composition (a) for its use

[0161] The subject of the present invention is therefore a composition (a) comprising propolis and at least one strain of probiotic for its use as a food supplement.

[0162] According to one variant, the composition (a) according to the invention can be used as a medical device.

[0163] Surprisingly, the inventors discovered that the combination of propolis with at least one strain of probiotic made it possible to provide a natural alternative to existing medications, in particular medications aimed at reducing intestinal inflammation, such as 5-aminosalicylic acid (5-ASA).

[0164] According to a preferred embodiment, the composition (a) according to the invention can be used to prevent and / or combat chronic inflammatory bowel diseases (IBD).

[0165] Preferably, composition (a) according to the invention can be used to prevent and / or combat intestinal inflammation.

[0166] The surprising combination of propolis with at least one probiotic strain has an improved effect on reducing intestinal inflammation. Thus, composition (a) according to any of the embodiments described above can be used to prevent and / or combat intestinal inflammation. Composition (a) can thus be used to improve the quality of life and / or relieve people suffering from intestinal inflammation.

[0167] Advantageously, the association between propolis and at least one strain of probiotic makes it possible to prevent and / or combat a large number of intestinal conditions and more particularly diseases or disorders associated with intestinal inflammation.

[0168] By diseases or disorders associated with intestinal inflammation we mean more particularly the following pathologies: * Inflammatory bowel disease (IBD): This term includes Crohn's disease and ulcerative colitis, but it is also used to refer to other, less common forms of inflammatory colitis, such as microscopic colitis and indeterminate colitis. IBD is characterized by chronic inflammation of the intestine, leading to symptoms such as abdominal pain, diarrhea, weight loss, and rectal bleeding. *Crohn's disease: This is a chronic inflammatory bowel disease that can affect any part of the digestive tract, from the mouth to the anus. Crohn's disease causes inflammation of the intestinal wall, leading to symptoms such as abdominal pain, diarrhea, weight loss, fatigue, and nausea. rectal movements. *Ulcerative colitis: Also known as ulcerative colitis, this is a chronic inflammatory disease that primarily affects the colon and rectum. It is characterized by ulcers and inflammation of the intestinal lining, resulting in symptoms such as abdominal cramps, bloody diarrhea, weight loss, and fatigue. *Irritable bowel syndrome (IBS): IBS is a functional disorder of the digestive system that causes abdominal pain, bloating, bowel movements (diarrhea or constipation), and changes in stool consistency. Although the exact cause of IBS is not clearly understood, intestinal inflammation and immune system dysfunction may play a role. *Celiac disease: This is an autoimmune disease in which the immune system reacts abnormally to the presence of gluten, a protein found in wheat, barley, and rye. Gluten ingestion causes inflammation of the intestinal lining in people with celiac disease, leading to symptoms such as abdominal pain, diarrhea, weight loss, and digestive problems. * Indeterminate inflammatory bowel disease (IBD): Some people may have symptoms and signs of intestinal inflammation, but do not meet the specific criteria for Crohn's disease or ulcerative colitis. These cases are then classified as indeterminate IBD. * Post-infectious irritable bowel syndrome (PIPS): PIPS develops after an intestinal infection, usually bacterial or viral gastroenteritis. It is characterized by symptoms similar to those of irritable bowel syndrome, such as abdominal pain, changes in bowel habits, and bloating, which persist for weeks or even months after infection. * Diverticulosis and diverticulitis: Diverticulosis is a condition where small pouches (diverticula) form in the wall of the colon. When these diverticula become inflamed or infected, it causes a condition called diverticulitis. Diverticulitis leads to inflammation of the colon, causing abdominal pain, fever, bowel movements, and bleeding. *Short bowel syndrome: This syndrome occurs when large portions of the intestine are surgically removed, usually due to disease or injury. It can lead to residual inflammation in the remaining parts of the intestine, as well as problems with nutrient absorption, causing chronic diarrhea, malnutrition, and electrolyte imbalances. *Autoimmune diseases with intestinal involvement: Some autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, can also lead to inflammation of the intestine. These diseases affect the immune system and can cause inflammation in different parts of the body, including the intestine. * Drug-induced intestinal inflammation: Certain medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and oral contraceptives, can cause inflammation of the intestinal lining in some susceptible individuals. This can lead to gastrointestinal symptoms such as abdominal pain, diarrhea, and ulceration. * Parkinson's disease: Parkinson's disease is a neurodegenerative disorder characterized by a decrease in dopamine in the brain, resulting in symptoms such as tremors, muscle rigidity, and coordination problems. Recent studies suggest a link between Parkinson's disease and intestinal inflammation. Chronic inflammation in the gut can trigger an inflammatory response in the brain, contributing to the development or progression of Parkinson's disease. * Alzheimer's disease: Alzheimer's disease is the most common form of dementia. It is characterized by the progressive loss of memory and cognitive function. Recent research has also highlighted a link between Alzheimer's disease and intestinal inflammation. Chronic inflammation of the intestine can promote the production of amyloid peptides, abnormal substances that accumulate in the brain and play a key role in the development of Alzheimer's disease. * Autism: Autism is a developmental disorder that affects communication, social interaction, and behavior. Although the precise mechanisms of autism are not yet fully understood, recent studies have shown a link between autism and intestinal inflammation. Alterations in the composition of the intestinal flora, as well as elevated inflammatory markers in the gut, have been observed in many individuals with autism. * Diseases associated with dysbiosis: Dysbiosis refers to an imbalance in the intestinal flora, where beneficial bacteria are reduced and harmful bacteria are favored. This imbalance can lead to various diseases, including certain inflammatory bowel diseases. * SIBO (Small Intestinal Bacterial Overgrowth): SIBO is a condition in which there is an excessive growth of bacteria in the small intestine. This condition can lead to intestinal inflammation and symptoms such as bloating, abdominal pain, and digestive problems.

[0169] According to one embodiment, composition (a) can be used as an inhibitor of the production of pro-inflammatory cytokines in intestinal cells.

[0170] Preferably, composition (a) can be used to reduce the production and / or secretion of pro-inflammatory cytokines in the intestine.

[0171] Preferably, the composition (a) according to the invention can be used to reduce the production and / or secretion in the intestine of at least one cytokine chosen from: TNF-alpha, INF-gamma, IL-6, IL-1beta and their mixture.

[0172] Composition (b)

[0173] According to another aspect, the invention relates to the association of a molecule naturally present within Baccharis propolis with at least one probiotic strain.

[0174] Thus, the invention relates to a composition (b) comprising artepillin C and at least one probiotic strain.

[0175] Surprisingly, the inventors discovered the combination of artepillin C and at least one strain of probiotic made it possible to reduce intestinal inflammation.

[0176] Artepillin C is one of the most active and beneficial compounds present in Baccharis propolis. Artepillin C is known for its many effects, including its antioxidant, anti-inflammatory, antimicrobial, and anticancer effects.

[0177] Preferably, composition (b) according to the invention comprises at least 1.5% of artepillin C by weight of the composition, even more preferably at least 2%.

[0178] According to one embodiment, artepillin C may be of natural or synthetic origin. Preferably, composition (b) according to the invention comprises artepillin C obtained from Baccharis propolis.

[0179] According to another embodiment, the composition (b) according to the invention comprises at least one probiotic strain chosen from Lactobacillus Paracasei, Lactobacillus Plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Bifidobacterium lactis, Bacillus subtilis and Enterococcus faecium.

[0180] Preferably, the composition (b) according to the invention comprises at least 107 CFU / g of composition (a) of at least one probiotic strain, even more preferably at least 108 CFU / g, in particular at least 5*109 CFU / g.

[0181] Preferably, composition (b) according to the invention comprises a strain of Lactobacillus Paracasei referenced LMG S-25516 from the BCCM (Belgian Co-ordinated Collections of Microorganism).

[0182] According to one embodiment, the composition (b) according to the invention comprises at least 107 CFU / g of composition (b) of the strain Lactobacillus Paracasei, preferably at least 108UFC / g, especially at least 2.5*109UFC / g.

[0183] Preferably, composition (b) according to the invention comprises a strain of Lactobacillus Plantarum referenced 1-5597 with the CNCM (National Collection of Cultures of Micro-Organisms).

[0184] According to one embodiment, the composition (b) according to the invention comprises at least 107 CFU / g of composition (a) of the strain Lactobacillus Plantarum, preferably at least 108 CFU / g, in particular at least 2.5*109 CFU / g.

[0185] According to a particular embodiment, the composition (b) according to the invention comprises artepillin C and a mixture consisting of at least two strains of probiotics.

[0186] According to one embodiment, composition (b) comprises a mixture of at least two strains of probiotics comprising: - between 40 and 60% by weight of the mixture of the Lactobacillus Paracasei strain, preferably of the LMG S-25516 (BCCM) strain; and - between 40 and 60% by weight of the mixture of the Lactobacillus Plantarum strain, preferably of the 1-5597 (CNCM) strain.

[0187] Preferably, composition (b) comprises a mixture of at least two strains of probiotics comprising 50% by weight of the mixture of the strain Lactobacillus Paracasei and 50% by weight of the mixture of the strain Lactobacillus Plantarum.

[0188] According to another embodiment, the composition (b) according to the invention comprises: - at least 107 CFU / g of composition (b) of the strain Lactobacillus Paracasei, preferably of the strain LMG S-25516 (BCCM); and - at least 107 CFU / g of composition (b) of the Lactobacillus Plantarum strain, preferably of the 1-5597 (CNCM) strain.

[0189] Preferably, composition (b) according to the invention comprises: - at least 2.5* 109 CFU / g of composition (b) of the strain Lactobacillus Paracasei, preferably of the strain LMG S-25516 (BCCM); and - at least 2.5* 109 CFU / g of composition (b) of the Lactobacillus Plantarum strain, preferably of the 1-5597 (CNCM) strain.

[0190] According to one embodiment, the composition (b) according to the invention comprises: - between 40 and 50% of propolis by weight of composition (b); - between 30 and 45% of probiotic strain by weight of composition (b).

[0191] According to one embodiment, the composition (b) according to the invention also comprises at least one prebiotic.

[0192] Advantageously, the use of prebiotics in composition (b) according to the invention reinforces the effect of the probiotics by guaranteeing them a source of energy.

[0193] Preferably, composition (b) comprises at least one prebiotic chosen from a bulking agent, an anti-caking agent and their mixture.

[0194] According to a particularly preferred embodiment, composition (b) comprises, as prebiotic, a plant fiber, preferably an acacia fiber and / or a carob fiber.

[0195] According to one embodiment, composition (b) consists of artepillin C, probiotics and prebiotics.

[0196] Preferably, composition (b) according to the invention comprises: - at least 1.5% of artepillin C by weight of composition (b); - between 15 and 30% of prebiotics by weight of composition (b); - between 30 and 45% of probiotics by weight of the composition (b).

[0197] According to a particularly preferred embodiment, composition (b) comprises: - at least 1.5% of artepillin C of synthetic origin by weight of composition (b) - between 15 and 30% of acacia fibers by weight of composition (b); - between 30 and 45% of at least one probiotic chosen from a strain of Lactobacillus Paracasei, a strain of Lactobacillus Plantarum and their mixture by weight of composition (b).

[0198] According to another particularly preferred embodiment, composition (a) comprises: - at least 1.5% of artepillin C by weight of composition (b); - between 15 and 30% of acacia fibers by weight of composition (b); - between 30 and 45% of a mixture of probiotics by weight of composition (b) comprising: *between 40 and 60% by weight of the mixture of the Lactobacillus Paracasei strain, preferably of the LMG S-25516 (BCCM) strain; and *between 40 and 60% by weight of the mixture of the Lactobacillus Plantarum strain, preferably of the 1-5597 strain (CNCM).

[0199] According to one embodiment, the composition (b) according to the invention is in powder form, in particular in a gastro-resistant capsule which can be administered orally.

[0200] According to one embodiment, the composition (b) according to the invention is capable of being obtained by a preparation process comprising the following steps: (a) Preparation of at least one strain of probiotic (b) Mixture of artepillin C with at least one prebiotic prepared in step (a).

[0201] According to a particular embodiment of the invention, composition (b) can be obtained by a preparation process comprising: - a step of extraction of artepillin C from Baccharis propolis; and / or - a step of chemical synthesis of artepillin C.

[0202] Process for obtaining composition fb):

[0203] According to another aspect, the invention relates to a method for preparing the composition (b) according to the invention, comprising the implementation of the following steps: (a) Preparation of at least one probiotic strain (b) Mixture of artepillin C with at least one prebiotic strain prepared in step (a).

[0204] In the context of the invention, artepillin C may be of natural or synthetic origin. When the artepillin C of step (b) is of natural origin, the artepillin C is extracted from propolis, preferably from Baccharis propolis.

[0205] According to a particular embodiment of the invention, the process for obtaining composition (b) comprises a step of extracting artepillin C from propolis, preferably from Baccharis propolis.

[0206] Preferably, the step of extracting artepillin C is a hydroalcoholic extraction.

[0207] Preferably, the preparation of step (a) comprises at least one strain of probiotic chosen from a strain of Lactobacillus Paracasei, a strain of Lactobacillus Plantarum and their mixture.

[0208] Preferably, the preparation of step (a) comprises at least one strain of probiotic chosen from a strain of Lactobacillus Plantarum referenced I-5597 (CNCM), a strain of Lactobacillus Paracasei referenced LMG S-25516 (BCCM) and their mixture.

[0209] According to one embodiment, step (a) consists of the preparation of a mixture comprising at least two strains of probiotic.

[0210] Preferably, the mixture of probiotics from step (a) comprises: - between 40 and 60% by weight of the mixture of the Lactobacillus Paracasei strain; and - between 40 and 60% by weight of the mixture of the Lactobacillus Plantarum strain.

[0211] According to a preferred embodiment, the mixture of probiotics of step (a) comprises a mixture of at least two strains of probiotics comprising: - 50% by weight of the mixture of the strain Lactobacillus Paracasei; and - 50% by weight of the mixture of the Lactobacillus Plantarum strain.

[0212] Preferably, at least one prebiotic from step (b) is chosen from a bulking agent, an anti-caking agent and their mixture.

[0213] According to a particularly preferred embodiment, the prebiotic of step (b) is a plant fiber, preferably an acacia fiber and / or a carob fiber.

[0214] Preferably, the mixing of step (c) is carried out using a paddle mixer.

[0215] According to one embodiment, the mixture of step (c) comprises: - at least 1.5% of artepillin C by weight of the mixture; - between 30 and 45% of probiotic strain by weight of the mixture.

[0216] According to another embodiment, the mixture of step (c) comprises: - at least 1.5% of artepillin C by weight of the mixture; - between 15 and 30% of prebiotics by weight of the mixture; and - between 30 and 45% of probiotics by weight of the mixture.

[0217] According to a particularly preferred embodiment, the mixture of step (c) comprises: - at least 1.5% of artepillin C by weight of the mixture; - between 15 and 30% of acacia fibers by weight of the mixture; - between 30 and 45% of at least one probiotic chosen from a strain of Lactobacillus Paracasei and / or a strain of Lactobacillus Plantarum by weight of the mixture.

[0218] According to a preferred embodiment, the mixture obtained at the end of step (c) is in solid form.

[0219] Composition (b) for its use

[0220] The present invention also relates to a composition (b) comprising artepillin C and at least one probiotic strain for its use as a medicament.

[0221] According to one variant, the composition (b) according to the invention can be used as a food supplement in humans or animals.

[0222] According to another variant, the composition (b) according to the invention can be used as a medical device.

[0223] Surprisingly, the inventors discovered that the combination of artepillin C with at least one strain of probiotic made it possible to provide an alternative to existing drugs, in particular drugs aimed at reducing intestinal inflammation, such as 5-aminosalicylic acid (5-ASA).

[0224] Preferably, composition (b) according to the invention can be used to prevent and / or combat intestinal inflammation.

[0225] The surprising combination of artepillin C with at least one probiotic strain shows an improved effect on reducing intestinal inflammation. Composition (b) can thus be used to prevent and / or combat functional intestinal disorders.

[0226] Thus, any of the embodiments of composition (b) described above can be used to prevent and / or combat intestinal inflammation.

[0227] According to one embodiment, the composition (b) comprising artepillin C and at least one probiotic strain chosen from a strain of Lactobacillus paracasei, a strain of Lactobacillus Plantarum and their mixture is used to reduce intestinal inflammation.

[0228] Advantageously, the association between propolis and at least one strain of probiotic makes it possible to prevent and / or combat a large number of intestinal conditions. and more particularly diseases or disorders associated with intestinal inflammation.

[0229] According to one embodiment, composition (b) can be used as an inhibitor of the production of pro-inflammatory cytokines in intestinal cells.

[0230] Preferably, composition (b) can be used to reduce the production and / or secretion of pro-inflammatory cytokines in the intestine.

[0231] Preferably, composition (b) according to the invention can be used to reduce the production and / or secretion in the intestine of at least one cytokine chosen from: TNF-alpha, INF-gamma, IL-6, IL-1beta and their mixture.

[0232] Composition (cl

[0233] According to another aspect, the invention relates to the association of a molecule naturally present in poplar propolis with at least one strain of probiotic.

[0234] Thus, the invention relates to a composition (c) comprising apigenin and at least one probiotic strain.

[0235] Surprisingly, the inventors discovered the combination of apigenin and at least one strain of probiotic made it possible to reduce intestinal inflammation.

[0236] According to one embodiment, the apigenin may be of natural or synthetic origin. Preferably, the composition (c) according to the invention comprises apigenin obtained from poplar propolis.

[0237] According to another embodiment, the composition (c) according to the invention comprises at least one probiotic strain chosen from Lactobacillus Paracasei, Lactobacillus Plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Bifidobacterium lactis, Bacillus subtilis and Enterococcus faecium.

[0238] Preferably, the composition (c) according to the invention comprises a strain of Lactobacillus Paracasei referenced LMG S-25516 from the BCCM (Belgian Co-ordinated Collections of Microorganism).

[0239] Preferably, composition (c) according to the invention comprises a strain of Lactobacillus Plantarum referenced 1-5597 with the CNCM (National Collection of Cultures of Micro-Organisms).

[0240] According to a particular embodiment, the composition (c) according to the invention comprises apigenin and a mixture consisting of at least two strains of probiotics.

[0241] According to one embodiment, composition (c) comprises a mixture of at least two strains of probiotics comprising 50% by weight of the mixture of the strain Lactobacillus Paracasei and 50% by weight of the mixture of the strain Lactobacillus Plantarum.

[0242] According to one embodiment, the composition (c) according to the invention also comprises at least one prebiotic.

[0243] According to one embodiment, the composition (c) according to the invention is in powder form, in particular in a gastro-resistant capsule that can be administered orally.

[0244] According to one embodiment, the composition (c) according to the invention is capable of being obtained by a preparation process comprising the following steps: (a) Preparation of at least one probiotic strain (c) Mixture of apigenin with at least one prebiotic prepared in step (a).

[0245] According to a particular embodiment of the invention, composition (c) can be obtained by a preparation process comprising: - a step of extracting apigenin from poplar propolis; and / or - a step of chemical synthesis of apigenin.

[0246] Composition (c) for its use

[0247] The present invention also relates to a composition (c) comprising apigenin and at least one probiotic strain for its use as a medicament.

[0248] According to one variant, the composition (c) according to the invention can be used as a food supplement in humans or animals.

[0249] According to another variant, the composition (c) according to the invention can be used as a medical device.

[0250] Surprisingly, the inventors discovered that the combination of apigenin with at least one strain of probiotic made it possible to provide an alternative to existing drugs, in particular drugs aimed at reducing intestinal inflammation, such as 5-aminosalicylic acid (5-ASA).

[0251] Preferably, composition (c) according to the invention can be used to prevent and / or combat intestinal inflammation.

[0252] The surprising combination of apigenin with at least one probiotic strain shows an improved effect on reducing intestinal inflammation. Composition (c) can thus be used to prevent and / or combat functional intestinal disorders.

[0253] Thus, any of the embodiments of composition (c) described above can be used to prevent and / or combat intestinal inflammation.

[0254] According to one embodiment, the composition (c) comprising apigenin and at least one probiotic strain chosen from a strain of Lactobacillus paracasei, a strain of Lactobacillus Plantarum and their mixture is used to reduce intestinal inflammation.

[0255] Advantageously, the association between propolis and at least one strain of probiotic makes it possible to prevent and / or combat a large number of intestinal conditions and more particularly diseases or disorders associated with intestinal inflammation.

[0256] According to one embodiment, composition (c) can be used as an inhibitor of the production of pro-inflammatory cytokines in intestinal cells.

[0257] Preferably, composition (c) can be used to reduce the production and / or secretion of pro-inflammatory cytokines in the intestine.

[0258] Preferably, composition (c) according to the invention can be used to reduce the production and / or secretion in the intestine of at least one cytokine chosen from: TNF-alpha, INF-gamma, IL-6, IL-1beta and their mixture.

[0259] Composition (d)

[0260] According to another aspect, the invention relates to the association of a molecule naturally present in poplar propolis with at least one strain of probiotic.

[0261] Thus, the invention relates to a composition (d) comprising caffeic acid phenethylester (CAPE) and at least one probiotic strain.

[0262] Surprisingly, the inventors discovered the combination of CAPE and at least one strain of probiotic made it possible to reduce intestinal inflammation.

[0263] According to one embodiment, the CAPE may be of natural or synthetic origin. Preferably, the composition (d) according to the invention comprises CAPE obtained from poplar propolis.

[0264] According to another embodiment, the composition (d) according to the invention comprises at least one probiotic strain chosen from Lactobacillus Paracasei, Lactobacillus Plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Bifidobacterium lactis, Bacillus subtilis and Enterococcus faecium.

[0265] Preferably, the composition (d) according to the invention comprises a strain of Lactobacillus Paracasei referenced LMG S-25516 from the BCCM (Belgian Co-ordinated Collections of Microorganism).

[0266] Preferably, composition (d) according to the invention comprises a strain of Lactobacillus Plantarum referenced 1-5597 with the CNCM (National Collection of Cultures of Micro-Organisms).

[0267] According to a particular embodiment, the composition (d) according to the invention comprises CAPE and a mixture consisting of at least two strains of probiotics.

[0268] According to one embodiment, composition (d) comprises a mixture of at least two strains of probiotics comprising 50% by weight of the mixture of the strain Lactobacillus Paracasei and 50% by weight of the mixture of the strain Lactobacillus Plantarum.

[0269] According to one embodiment, the composition (d) according to the invention also comprises at least one prebiotic.

[0270] According to one embodiment, the composition (d) according to the invention is in powder form, in particular in a gastro-resistant capsule which can be administered by oral.

[0271] According to one embodiment, the composition (d) according to the invention is capable of being obtained by a preparation process comprising the following steps: (a) Preparation of at least one probiotic strain (d) Mixture of CAPE with at least one prebiotic prepared in step (a).

[0272] According to a particular embodiment of the invention, composition (d) can be obtained by a preparation process comprising: - a step of extraction of CAPE from poplar propolis; and / or - a step of chemical synthesis of CAPE.

[0273] Composition (d) for its use

[0274] The present invention also relates to a composition (d) comprising CAPE and at least one probiotic strain for its use as a medicament.

[0275] According to one variant, the composition (d) according to the invention can be used as a food supplement in humans or animals.

[0276] According to another variant, the composition (d) according to the invention can be used as a medical device.

[0277] Surprisingly, the inventors discovered that the combination of CAPE with at least one strain of probiotic made it possible to provide an alternative to existing drugs, in particular drugs aimed at reducing intestinal inflammation, such as 5-aminosalicylic acid (5-ASA).

[0278] Preferably, composition (d) according to the invention can be used to prevent and / or combat intestinal inflammation.

[0279] The surprising combination of CAPE with at least one probiotic strain shows an improved effect on reducing intestinal inflammation. Composition (d) can thus be used to prevent and / or combat functional intestinal disorders.

[0280] Thus, any of the embodiments of composition (d) described above can be used to prevent and / or combat intestinal inflammation.

[0281] According to one embodiment, the composition (d) comprising CAPE and at least one probiotic strain chosen from a strain of Lactobacillus paracasei, a strain of Lactobacillus Plantarum and their mixture is used to reduce intestinal inflammation.

[0282] Advantageously, the association between propolis and at least one strain of probiotic makes it possible to prevent and / or combat a large number of intestinal conditions and more particularly diseases or disorders associated with intestinal inflammation.

[0283] According to one embodiment, composition (d) can be used as an inhibitor of the production of pro-inflammatory cytokines in in- testinals.

[0284] Preferably, composition (d) can be used to reduce the production and / or secretion of pro-inflammatory cytokines in the intestine.

[0285] Preferably, composition (d) according to the invention can be used to reduce the production and / or secretion in the intestine of at least one cytokine chosen from: TNF-alpha, INF-gamma, IL-6, IL-1beta and their mixture.

[0286] Composition (e)

[0287] According to another aspect, the invention relates to the association of a molecule naturally present in poplar propolis with at least one strain of probiotic.

[0288] Thus, the invention relates to a composition (e) comprising Galangin and at least one probiotic strain.

[0289] Surprisingly, the inventors discovered the combination of Galangin and at least one strain of probiotic made it possible to reduce intestinal inflammation.

[0290] According to one embodiment, the Galangin may be of natural or synthetic origin. Preferably, the composition (e) according to the invention comprises Galangin obtained from poplar propolis.

[0291] According to another embodiment, the composition (e) according to the invention comprises at least one probiotic strain chosen from Lactobacillus Paracasei, Lactobacillus Plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Bifidobacterium lactis, Bacillus subtilis and Enterococcus faecium.

[0292] Preferably, the composition (e) according to the invention comprises a strain of Lactobacillus Paracasei referenced LMG S-25516 from the BCCM (Belgian Co-ordinated Collections of Microorganism).

[0293] Preferably, the composition (e) according to the invention comprises a strain of Lactobacillus Plantarum referenced 1-5597 with the CNCM (National Collection of Cultures of Micro-Organisms).

[0294] According to a particular embodiment, the composition (e) according to the invention comprises Galangin and a mixture consisting of at least two strains of probiotics.

[0295] According to one embodiment, the composition (e) comprises a mixture of at least two strains of probiotics comprising 50% by weight of the mixture of the strain Lactobacillus Paracasei and 50% by weight of the mixture of the strain Lactobacillus Plantarum.

[0296] According to one embodiment, the composition (e) according to the invention also comprises at least one prebiotic.

[0297] According to one embodiment, the composition (e) according to the invention is in powder form, in particular in a gastro-resistant capsule which can be administered orally.

[0298] According to one embodiment, the composition (e) according to the invention is capable of being obtained by a preparation process comprising the following steps: (a) Preparation of at least one strain of probiotic (e) Mixture of Galangin with at least one prebiotic prepared in step (a).

[0299] According to a particular embodiment of the invention, composition (e) is capable of being obtained by a preparation process comprising: - a step of extraction of Galangin from poplar propolis; and / or - a step of chemical synthesis of Galangin.

[0300] Composition (e) for its use

[0301] The present invention also relates to a composition (e) comprising Galangin and at least one probiotic strain for its use as a medicament.

[0302] According to one variant, the composition (e) according to the invention can be used as a food supplement in humans or animals.

[0303] According to another variant, the composition (e) according to the invention can be used as a medical device.

[0304] Surprisingly, the inventors discovered that the combination of Galangin with at least one strain of probiotic made it possible to provide an alternative to existing drugs, in particular drugs aimed at reducing intestinal inflammation, such as 5-aminosalicylic acid (5-ASA).

[0305] Preferably, the composition (e) according to the invention can be used to prevent and / or combat intestinal inflammation.

[0306] The surprising combination of Galangin with at least one probiotic strain has an improved effect on reducing intestinal inflammation. Composition (e) can thus be used to prevent and / or combat functional intestinal disorders.

[0307] Thus, any of the embodiments of composition (e) described above can be used to prevent and / or combat intestinal inflammation.

[0308] According to one embodiment, the composition (e) comprising Galangin and at least one probiotic strain chosen from a strain of Lactobacillus paracasei, a strain of Lactobacillus Plantarum and their mixture is used to reduce intestinal inflammation.

[0309] Advantageously, the association between propolis and at least one strain of probiotic makes it possible to prevent and / or combat a large number of intestinal conditions and more particularly diseases or disorders associated with intestinal inflammation.

[0310] According to one embodiment, composition (e) can be used as an inhibitor of the production of pro-inflammatory cytokines in intestinal cells.

[0311] Preferably, composition (e) can be used to reduce the production and / or secretion of pro-inflammatory cytokines in the intestine.

[0312] Preferably, the composition (e) according to the invention can be used to reduce the production and / or secretion in the intestine of at least one cytokine chosen from: TNF-alpha, INF-gamma, IL-6, IL-1beta and their mixture.

[0313] Composition (fl

[0314] According to another aspect, the invention relates to the association of a molecule naturally present in poplar propolis with at least one probiotic strain.

[0315] Thus, the invention relates to a composition (f) comprising Chrysin and at least one probiotic strain.

[0316] Surprisingly, the inventors discovered the combination of Chrysin and at least one strain of probiotic made it possible to reduce intestinal inflammation.

[0317] According to one embodiment, the Chrysin may be of natural or synthetic origin. Preferably, the composition (f) according to the invention comprises Chrysin obtained from poplar propolis.

[0318] According to another embodiment, the composition (f) according to the invention comprises at least one probiotic strain chosen from Lactobacillus Paracasei, Lactobacillus Plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Bifidobacterium lactis, Bacillus subtilis and Enterococcus faecium.

[0319] Preferably, the composition (f) according to the invention comprises a strain of Lactobacillus Paracasei referenced LMG S-25516 from the BCCM (Belgian Co-ordinated Collections of Microorganism).

[0320] Preferably, the composition (f) according to the invention comprises a strain of Lactobacillus Plantarum referenced 1-5597 with the CNCM (National Collection of Cultures of Micro-Organisms).

[0321] According to a particular embodiment, the composition (f) according to the invention comprises Chrysin and a mixture consisting of at least two strains of probiotics.

[0322] According to one embodiment, the composition (f) comprises a mixture of at least two strains of probiotics comprising 50% by weight of the mixture of the strain Lactobacillus Paracasei and 50% by weight of the mixture of the strain Lactobacillus Plantarum.

[0323] According to one embodiment, the composition (f) according to the invention also comprises at least one prebiotic.

[0324] According to one embodiment, the composition (f) according to the invention is in powder form, in particular in a gastro-resistant capsule which can be administered orally.

[0325] According to one embodiment, the composition (f) according to the invention is capable to be obtained by a preparation process comprising the following steps: (a) Preparation of at least one probiotic strain (f) Mixture of Chrysin with at least one prebiotic prepared in step (a).

[0326] According to a particular embodiment of the invention, composition (f) is capable of being obtained by a preparation process comprising: - a step of extracting Chrysin from poplar propolis; and / or - a step of chemical synthesis of Chrysin.

[0327] Composition (f) for its use

[0328] The present invention also relates to a composition (f) comprising Chrysin and at least one probiotic strain for its use as a medicament.

[0329] According to one variant, the composition (f) according to the invention can be used as a food supplement in humans or animals.

[0330] According to another variant, the composition (f) according to the invention can be used as a medical device.

[0331] Surprisingly, the inventors discovered that the association of Chrysin with at least one strain of probiotic made it possible to provide an alternative to existing drugs, in particular drugs aimed at reducing intestinal inflammation, such as 5-aminosalicylic acid (5-ASA).

[0332] Preferably, the composition (f) according to the invention can be used to prevent and / or combat intestinal inflammation.

[0333] The surprising combination of Chrysin with at least one probiotic strain shows an improved effect on reducing intestinal inflammation. Composition (f) can thus be used to prevent and / or combat functional intestinal disorders.

[0334] Thus, any of the embodiments of composition (f) described above can be used to prevent and / or combat intestinal inflammation.

[0335] According to one embodiment, the composition (f) comprising Chrysin and at least one probiotic strain chosen from a strain of Lactobacillus paracasei, a strain of Lactobacillus Plantarum and their mixture is used to reduce intestinal inflammation.

[0336] Advantageously, the association between propolis and at least one strain of probiotic makes it possible to prevent and / or combat a large number of intestinal conditions and more particularly diseases or disorders associated with intestinal inflammation.

[0337] According to one embodiment, composition (f) can be used as an inhibitor of the production of pro-inflammatory cytokines in intestinal cells.

[0338] Preferably, composition (f) can be used to reduce the production and / or secretion of pro-inflammatory cytokines in the intestine.

[0339] Preferably, the composition (f) according to the invention can be used to reduce the production and / or secretion in the intestine of at least one cytokine chosen from: TNF-alpha, INF-gamma, IL-6, IL-1beta and their mixture.

[0340] Composition (g)

[0341] According to another aspect, the invention relates to the association of a molecule naturally present in poplar propolis with at least one strain of probiotic.

[0342] Thus, the invention relates to a composition (g) comprising Pinocembrin and at least one probiotic strain.

[0343] Surprisingly, the inventors discovered the combination of Pinocembrin and at least one strain of probiotic made it possible to reduce intestinal inflammation.

[0344] According to one embodiment, the Pinocembrin may be of natural or synthetic origin. Preferably, the composition (g) according to the invention comprises Pinocembrin obtained from poplar propolis.

[0345] According to another embodiment, the composition (g) according to the invention comprises at least one probiotic strain chosen from Lactobacillus Paracasei, Lactobacillus Plantarum, Lactobacillus rhamnosus, Lactobacillus helveticus, Bifidobacterium lactis, Bacillus subtilis and Enterococcus faecium.

[0346] Preferably, the composition (g) according to the invention comprises a strain of Lactobacillus Paracasei referenced LMG S-25516 from the BCCM (Belgian Co-ordinated Collections of Microorganism).

[0347] Preferably, the composition (g) according to the invention comprises a strain of Lactobacillus Plantarum referenced 1-5597 with the CNCM (National Collection of Cultures of Micro-Organisms).

[0348] According to a particular embodiment, the composition (g) according to the invention comprises Pinocembrin and a mixture consisting of at least two strains of probiotics.

[0349] According to one embodiment, the composition (g) comprises a mixture of at least two strains of probiotics comprising 50% by weight of the mixture of the strain Lactobacillus Paracasei and 50% by weight of the mixture of the strain Lactobacillus Plantarum.

[0350] According to one embodiment, the composition (g) according to the invention also comprises at least one prebiotic.

[0351] According to one embodiment, the composition (g) according to the invention is in powder form, in particular in a gastro-resistant capsule that can be administered orally.

[0352] According to one embodiment, the composition (g) according to the invention is capable to be obtained by a preparation process comprising the following steps: (a) Preparation of at least one probiotic strain (g) Mixture of Pinocembrin with at least one prebiotic prepared in step (a).

[0353] According to a particular embodiment of the invention, the composition (g) is capable of being obtained by a preparation process comprising: - a step of extracting Pinocembrin from poplar propolis; and / or - a step of chemical synthesis of Pinocembrin.

[0354] Composition (g) for its use

[0355] The present invention also relates to a composition (g) comprising Pinocembrin and at least one probiotic strain for its use as a medicament.

[0356] According to one variant, the composition (g) according to the invention can be used as a food supplement in humans or animals.

[0357] According to another variant, the composition (g) according to the invention can be used as a medical device.

[0358] Surprisingly, the inventors discovered that the combination of Pinocembrin with at least one strain of probiotic made it possible to provide an alternative to existing drugs, in particular drugs aimed at reducing intestinal inflammation, such as 5-aminosalicylic acid (5-ASA).

[0359] Preferably, the composition (g) according to the invention can be used to prevent and / or combat intestinal inflammation.

[0360] The surprising combination of Pinocembrin with at least one probiotic strain shows an improved effect on reducing intestinal inflammation. Composition (g) can thus be used to prevent and / or combat functional intestinal disorders.

[0361] Thus, any of the embodiments of the composition (g) described above can be used to prevent and / or combat intestinal inflammation.

[0362] According to one embodiment, the composition (g) comprising Pinocembrin and at least one probiotic strain chosen from a strain of Lactobacillus paracasei, a strain of Lactobacillus Plantarum and their mixture is used to reduce intestinal inflammation.

[0363] Advantageously, the association between propolis and at least one strain of probiotic makes it possible to prevent and / or combat a large number of intestinal conditions and more particularly diseases or disorders associated with intestinal inflammation.

[0364] According to one embodiment, composition (g) can be used as an inhibitor of the production of pro-inflammatory cytokines in intestinal cells.

[0365] Preferably, composition (g) can be used to reduce the production and / or secretion of pro-inflammatory cytokines in the intestine.

[0366] Preferably, the composition (g) according to the invention can be used to reduce the production and / or secretion in the intestine of at least one cytokine chosen from: TNF-alpha, INF-gamma, IL-6, IL-1beta and their mixture. Examples

[0367] Example 1: Measurement of the effect of composition (a) and composition (b) according to the invention on the reduction of intestinal inflammation

[0368] Cell culture and treatments:

[0369] Caco-2 intestinal cells were cultured in MEM supplemented with 10% fetal bovine serum, 1% antibiotics (penicillin 100 IU / ml and streptomycin 50 pg / ml), L-Glu and incubated at 37 °C in a humidified chamber containing 5% CO2.

[0370] Then, the cells were cultured at a density of 50 x 103 cells per well for 21 days until their differentiation. The integrity of the monolayer was assessed daily by microscopic visualization.

[0371] After their differentiation, Caco-2 cells were pretreated with: * raw Baccharis propolis at 2.5 or 5pg / ml; * a mixture of Lactobacillus Paracasei and Lactobacillus Plantarum in a ratio of 1:1 at concentrations of 106 and 107 CFU / mL. *Artepillin C at 2.5 and 7.5 pM; and * their combinations.

[0372] The results are shown in [Fig.l] and [Fig.2].

[0373] The Baccharis propolis used in this example is obtained by cold grinding of raw propolis.

[0374] The strain of Lactobacillus Plantarum used in this example is referenced I-5597(CNCM) and the strain of Lactobacillus Paracasei is referenced LMG S-25516 (BCCM)

[0375] To induce an inflammatory state, Caco-2 cells were then treated with LPS at a concentration of 0.5 pg / ml for 4 hours. N-acetyl-5-Aminosalicylic acid (5-ASA) was used as a control against the inflammatory state. After LPS treatment, supernatants were collected (volume of 250 pL) and stored at -80 °C until further analyses.

[0376] Cytokine Measurement and Statistical Analysis

[0377] 1) Absolute TNF-alpha levels

[0378] The level of human TNF-alpha was assayed using an ELISA kit according to the manufacturer's instructions.

[0379] 2) Relative levels of cytokines

[0380] Cytokine levels were normalized and expressed as % of the levels obtained with LPS alone.

[0381] 3) Statistical analysis

[0382] Statistical analyses were carried out using Sigma Plot software. Different tests can be carried out depending on the data: ANOVA followed by the Dunnet test, if the application conditions are respected.

[0383] The results presented in [Fig.l] show that the crude extract of Baccharis propolis exerts an inhibitory activity on the production of a pro-inflammatory cytokine in Caco-2 intestinal cells. Both probiotic strains (L.Paracasei as well as L / Plantarum) also showed an anti-inflammatory effect.

[0384] Finally, the combination of Baccharis propolis and the two strains of probiotics showed an improved effect on the inhibition of the production of pro-inflammatory cytokines, more particularly on the production of TNF-alpha.

[0385] The results presented in [Fig.2] show that Artepillin C exerts an inhibitory activity on the production of a pro-inflammatory cytokine in Caco-2 intestinal cells. Both probiotic strains (L.Paracasei as well as L / Plantarum) also showed an anti-inflammatory effect.

[0386] Finally, the combination of Artepillin C and the two strains of probiotics showed an improved effect on the inhibition of the production of pro-inflammatory cytokines, more particularly on the production of TNF-alpha.

Claims

Claims

1. Composition (a) comprising propolis and at least one probiotic strain.

2. Composition (a) according to the preceding claim, characterized in that the propolis is chosen from poplar propolis, Baccharis propolis, Dalbergia propolis and mixtures thereof.

3. Composition (a) according to one of the preceding claims, characterized in that the propolis is in raw form or in extract form.

4. Composition (a) according to one of the preceding claims, characterized in that at least one strain of probiotic is chosen from Lactobacillus paracasei, Lactobacillus Plantarum and their mixture.

5. Composition (a) according to one of the preceding claims, characterized in that it comprises at least 107 CFU / g of composition (a) of probiotics.

6. Composition (a) according to one of the preceding claims, characterized in that it comprises: *at least 107 CFU / g of composition (a) of the strain Lactobacillus Paracaséi; and / or *at least 107 CFU / g of composition (a) of the strain Lactobacillus Plantarum.

7. Composition (a) according to one of the preceding claims, characterized in that it comprises: - between 40 and 50% by weight of propolis relative to composition (a); - between 30 and 45% by weight of probiotics relative to composition (a).

8. Composition (a) according to one of the preceding claims, characterized in that it also comprises at least one prebiotic.

9. Composition (a) according to the preceding claim, characterized in that at least one prebiotic is chosen from a bulking agent, an anti-caking agent and their mixture.

10. Composition (a) according to the invention according to one of claims 8 or 9, characterized in that at least one prebiotic is a plant fiber, preferably an acacia fiber.

11. Composition (a) according to one of the preceding claims, characterized in that the propolis comprises at least 10% of total polyphenols relative to the weight of the propolis, preferably at least 15% of PPTX.

12. Composition according to one of the preceding claims, characterized in that it is in powder form.

13. Composition according to one of the preceding claims, characterized in that it is capable of being obtained by a preparation process comprising the implementation of the following steps: (a) Preparation of propolis (b) Preparation of at least one strain of probiotic (d) Mixture of the propolis prepared in step (a), of at least one strain of probiotic prepared in step (b).

14. Process for preparing a composition according to one of claims 1 to 13, characterized by carrying out the following steps: (a) Preparation of propolis (b) Preparation of at least one strain of probiotic (d) Mixture of the propolis prepared in step (a), of at least one strain of probiotic prepared in step (b).

15. Method according to the preceding claim, characterized in that the propolis of step (a) is chosen from poplar propolis, Baccharis propolis, Dalbergia propolis and mixtures thereof.

16. Method according to one of claims 14 or 15, characterized in that at least one probiotic strain of step (b) is chosen from Lactobacillus Paracasei, Lactobacillus Plantarum and their mixture.

17. Method according to one of claims 14 to 16, characterized in that at least one prebiotic of step (b) is chosen from an anti-agglomerating agent, a bulking agent and their mixture.

18. Method according to one of claims 14 to 17, characterized in that the mixture of step (d) comprises: *between 30 and 50% by weight of propolis relative to the weight of the mixture; *between 30 and 45% by weight of the mixture of probiotics

19. Composition (a) according to one of claims 1 to 11, for its use as a medicament.

20. Composition for its use according to the preceding claim, for preventing and / or combating intestinal inflammation.

21. Composition for its use according to the preceding claim, in the treatment of diseases or disorders associated with intestinal inflammation chosen from: chronic inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis, irritable bowel syndrome, celiac disease, undetermined inflammatory bowel diseases, post-infectious irritable bowel syndrome, diverticulosis, short bowel syndrome, autoimmune diseases, drug-induced intestinal inflammation, Parkinson's disease, Alzheimer's disease, autism, diseases associated with dysbiosis, and SIBO.

22. Composition for its use according to one of claims 19 to 21, as an inhibitor of the production and / or secretion of pro-inflammatory cytokines in the intestine.

23. Composition for its use according to the preceding claim, characterized in that at least one pro-inflammatory cytokine is chosen from TNF-alpha, INF-gamma, IL-6, IL-lbeta and their mixture.

Images