Composition including safranal and probiotics

Abstract

The present invention relates to a composition comprising at least one plant extract comprising at least 0.2% safranal, in particular from Crocus sativus and at least one probiotic bacterium and / or probiotic yeast, as well as its uses.

Description

Title of the invention: Composition comprising safranal and probiotics

[0001] The present invention relates to a composition comprising at least one plant extract containing at least 0.2% safranal as measured by HPLC, in particular an extract of Crocus sativus, and at least one probiotic bacterium and / or probiotic yeast, as well as its uses. The composition according to the invention can be used as a nutritional or pharmaceutical product in numerous applications, in particular to improve functional bowel disorders (FBD), sleep disorders, immune disorders, or stress in humans and animals.

[0002] IBS, also known as irritable bowel syndrome, refers to a chronic intestinal disorder whose pathophysiological mechanisms are not yet fully understood and which affects 9 to 23% of the population (Saha L, "Irritable bowel syndrome: pathogenesis, diagnosis, treatment, and evidence-based medicine." World J Gastroenterol. 2014 Jun 14;20(22):6759-73). It is a multifactorial condition involving visceral hypersensitivity, abnormal gastric motility, and altered intestinal permeability.

[0003] It has recently been shown that immune system disorders, serotonergic abnormalities in the gut, disturbances of the gut microbiota, and psychological factors such as stress or anxiety can also contribute to the development of IBS. The symptoms of IBS include abdominal pain or discomfort, bloating, and bowel movement disorders such as diarrhea, constipation, or alternating between the two. The overall symptoms of IBS can significantly impair quality of life by inducing sleep disturbances (Fass R, Fullerton S, Tung S, Mayer EA. "Sleep disturbances in clinical patients with functional bowel disorders". Am J Gastroenterol. 2000; 95: 1195-2000; Bellini M, Gemignani A, Gambaccini D, et al. "Evaluation of latent links between irritable bowel syndrome and sleep quality". World J Gastroenterol. 2011; 17: 5089-5096) or a decrease in self-esteem.

[0004] Interestingly, sleep disturbances have been shown not only to be a consequence of IBS but also a risk factor for the onset of the disease (Creed F, “Review article: the incidence and risk factors for irritable bowel syndrome in population-based studies,” Aliment Pharmacol Ther. 2019 Sep;50(5):507-516). Thus, the risk of developing IBS is 1.6 times higher in people with sleep disturbances compared to individuals without them (Vege SS, Locke GR 3rd, Weaver AL, Farmer SA, Melton LJ 3rd, Talley NJ. “Functional gastrointestinal disorders among people with sleep disturbances: a population-based study”. Mayo Clin Proc. 2004;79:1501-1506).

[0005] A strong correlation has also been observed between the severity of IBS and psychiatric disorders, particularly depression and anxiety. A review on the psychosocial determinants of IBS reports a significant increase in stress scores just before the onset of the illness (Surdea-Blaga T, Bâban A, Dumitrascu DL, “Psychosocial determinants of irritable bowel syndrome, World J Gastroenterol”. 2012 Feb21; 18(7):616-26).

[0006] These observations clearly demonstrate the existence of a communication system between the brain and the gut. The underlying pathophysiological mechanisms are now partly understood, but much research remains to be done. Besides the humoral pathway, one communication route of the gut-brain axis is the nervous system. Indeed, the digestive tract, in addition to its intrinsic innervation, communicates with the brain bidirectionally via sympathetic and parasympathetic afferents and efferents.

[0007] The measurement of autonomic nervous system (ANS) activity, through heart rate variability (HRV) (a measurement commonly used to assess overall ANS activity), has therefore been the subject of several studies in IBS. In particular, a decrease in HRV has been shown in patients with IBS compared to healthy subjects (Polster A, Friberg P, Gunterberg V, Ôhman L, Le Nevé B, Tôrnblom H, Cvijovic M, Simren M, “Heart rate variability characteristics of patients with irritable bowel syndrome and associations with symptoms”, Neurogas-troenterol Motil. 2018 Jul;30(7)). Interestingly, a decrease in HRV is also observed in subjects with depression or in cases of stress (Hartmann R, Schmidt FM, Sander C, Hegerl U, “Heart Rate Variability as Indicator of Clinical State in Depression”, Front Psychiatry. 2019 Jan 17;9:735).

[0008] It is therefore of great interest to develop solutions, acting on the communication pathways of the gut-brain axis, to prevent and combat the symptoms and risk factors of IBS, in order to improve the quality of life of those affected.

[0009] Given that a disturbed gut microenvironment (dysbiosis), induced by chronic stress for example, promotes the development and maintenance of IBS, manipulating the gut microbiota to improve IBS symptoms is now part of new treatment strategies. Several different approaches have been studied to improve the composition of the gut microbiota. Dietary modifications, including fiber supplementation, prebiotics, and probiotics, have been shown to improve symptoms and gut microbiota composition in IBS. In the field of research evaluating the Regarding the effects of probiotics, lactic acid bacteria such as Lactobacillus and Bifidobacteria have been the most frequently studied.

[0010] It has also been shown that the use of several strains of the same species or of several bacteria of different species allowed an improvement in overall symptoms of IBS compared to the use of strains alone (Ortiz-Lucas M, Tobias A, Saz P, Sebastian JJ. “Effects of probiotic species on irritable bowel syndrome symptoms: a bring up to date metaanalysis”. Rev Esp Enferm Dig. 2013; 105(1): 19 - 36). The use of probiotics containing Lactobacillus allows for the significant reduction of certain specific symptoms such as abdominal pain or flatulence and improves quality of life (Asha MZ, Khalil SFH, Efficacy and Safety of Probiotics, Prebiotics and Synbiotics in the Treatment of Irritable Bowel Syndrome: A systematic review and meta-analysis, Sultan Qaboos Univ Med J. 2020 Feb;20(l):el3-e24).

[0011] In particular, it has been shown that the mixture of Bifidobacterium animalis, Lactobacillus acidophilus, Lactobacillus delbrueckii and Spretococcus thermophilus used at a dose of 4*10A9 CFU, twice daily for a period of 4 weeks, reduced abdominal pain, bloating and provided satisfactory relief of general symptoms compared to taking a placebo, in individuals suffering from IBS (Jafari E, Vahedi H, Merat S et al. (2014) “Therapeutic effects, tolerability and safety of a multi-strain probiotic in Iranian adults with irritable bowel syndrome and bloating”. Arch Iran Med 17, 466-470).

[0012] Recent studies have also demonstrated the benefits of using probiotics in depression (Smith KS, Greene MW, Babu JR, Frugé AD, Psychobiotics as treatment for anxiety, depression, and related symptoms: a systematic review. Nutr Neurosci. 2019 Dec 20:1-15), anxiety, stress, and sleep. Other studies have also evaluated the beneficial role of probiotics on the autonomic nervous system, particularly on HRV.

[0013] However, there is currently no recommendation in the prior art on specific probiotics to be used to combat the symptoms of IBS (McKenzie YA, Bowyer RK, Leach H, Gulia P, Horobin J, O'Sullivan NA, Pettitt C, Reeves LB, Seamark L, Williams M, Thompson J, Lomer MC; (IBS Dietetic Guideline Review Group on behalf of Gastroenterology Specialist Group of the British Dietetic Association, British Dietetic Association systematic review and evidence-based practice guidelines for the dietary management of irritable bowel syndrome in adults (2016 update), J Hum Nutr Diet. 2016 Oct;29(5):549-75).

[0014] Certain compounds or extracts of plant origin have also shown efficacy on symptoms or risk factors related to IFT, in particular compounds or extracts of crocus sativus.

[0015] Selective serotonin reuptake inhibitors (SSRIs) are antidepressant agents used in the treatment of IBS. Among them, fluoxetine has shown efficacy at a dose of 20 mg / day (Trinkley, KE & Nahata, MC. "Medication management of irritable bowel syndrome." Digestion 89, 253-267 (2014)). However, SSRIs are often associated with side effects, whereas plant extracts provide similar activity without inducing adverse effects. In a randomized, double-blind clinical trial, daily supplementation with 30 mg of saffron extract showed an effect equivalent to 20 mg of fluoxetine in improving the quality of life of 66 people suffering from IBS.

[0016] Saffron has also shown efficacy on risk factors related to IBS with improved sleep quality (Shahdadi, H., Balouchi, A. & Deh-ghanmehr, S. Effect of saffron oral capsule on anxiety and quality of sleep of diabetic patients in a tertiary healthcare facility in southeastern Iran: A quasi-experimental study. Trop. J. Pharm. Res. 16, 2749-2753 (2017); Milajerdi, A. et al. The effects of alcoholic extract of saffron (Crocus satious L.) on mild to moderate comorbid depression-anxiety, sleep quality, and life satisfaction in type 2 diabetes mellitus: A double-blind, randomized and placebo-controlled clinical trial. Complément Ther Med 41, 196-202 (2018)), and improved mood disorders (Akhondzadeh, S. et al. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial. Phytother Res 19, 148-151 (2005).) as well as increased immune system activity (Kianbakht, S.& Ghazavi, A. Im-munomodulatory effects of saffron: A randomized double-blind placebo-controlled clinical trial. Phyther. Res. 25, 1801-1805 (2011)). .

[0017] More specifically, the effects of saffron in minimizing risk factors for the development of IBS are associated with the action of safranal, as reported in studies on sleep (Liu, Z. et al. Safranal enhances non-rapid eye movement sleep in pen-tobarbital-treated mice. CNS Neurosci Ther 18, 623-630 (2012)), stress (Fukui, H., Toyoshima, K. & Komaki, R. Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus). Phytomedicine 18, 726-730 (2011)) and immunity (Bukhari SI, Pattnaik B, Rayees S, Kaul S, Dhar MK, Safranal of Crocus sativus L. inhibits inducible nitric oxide synthase and attenuates asthma in a mouse model of asthma. Phytother Res. 29(4), 617-27 (2015)). In humans under stress, supplementation with 30mg of saffron standardized to 0.2% safranal has shown its beneficial role in maintaining HRV.

[0018] However, there is still a significant need for a product capable of preventing or treating IBS, sleep disorders, immunity or stress with improved efficacy compared to the prior art.

[0019] The objective of the present invention is therefore to meet this need by proposing a new nutritional or pharmaceutical composition comprising at least one specific plant extract comprising at least 0.2% safranal by weight relative to the total dry matter weight, measured by HPLC method, and at least one probiotic bacterium and / or probiotic yeast to primarily prevent or treat IBS, sleep disorders, immunity and stress.

[0020] In the prior art, effects on IBS, sleep disorders, immunity, stress of an extract of Crocus Sativus or of a probiotic bacterium, yeast or mixture of strains individually have been suggested, but no such composition has been described.

[0021] Surprisingly, while it is known from the prior art that saffron has antimicrobial effects (Nanasombat et al. 2014; Liu et al. 2017; Nadir et al. 2019; Ambrosio et al. 2020) and therefore that saffron is not a priori compatible with use with bacteria, the inventors observed that the specific combination of probiotic bacteria and / or yeasts and a specific plant extract containing safranal, such as saffron, provides an improved effect on IBS, sleep disorders, immunity, and stress in humans or animals. Furthermore, the particular quantity of active molecules, and especially safranal, found in the plant extract also enhances the effect of the composition.

[0022] Preferably, the plant extract incorporated into the composition according to the invention is an extract of Crocus sativus comprising at least 0.2% of safranal by weight relative to the total weight of the dry matter, measured by HPLC method.

[0023] The probiotic bacterium integrated into the composition according to the invention is preferably chosen from bacteria of the genera Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Enterococcus, Pediococcus and Escherichia.

[0024] The probiotic yeast integrated into the composition according to the invention is preferably chosen from yeasts of the genus Saccharomyces.

[0025] The invention also relates to non-therapeutic uses of the present composition.

[0026] Other features and advantages will become apparent from the detailed description of the invention which will follow. Detailed description of the invention

[0027] I. Definitions

[0028] For the purposes of this invention, "animal" means any animal except human beings (Men).

[0029] For the purposes of this invention, "nutritional composition" means any mixture of food compounds intended for ingestion and comprising at least 0.2% of safranal measured by HPLC, in particular an extract of Crocus sativus, and at least one bacterium Probiotics and / or probiotic yeast. Nutritional compositions include food compositions or foods, or food supplements.

[0030] For the purposes of this invention, "plant extract" means all or part of said plant, or at least one molecule or a set of several molecules derived from all or part of a plant. This may be a specific selection of native molecules present in the plant or molecules obtained by any type of transformation of said native molecules. The raw material used to obtain the extract may consist of all or part of a plant containing safranal. If the plant containing safranal is Crocus sativus, the plant extract according to the invention may be all or part of Crocus sativus or may be obtained in particular from saffron stigmas and / or petals and / or bulbs, preferably from stigmas.

[0031] The extraction processes are well known to those skilled in the art. One can notably mention the process consisting of the implementation of the following steps: use of stigmas of Crocus sativus, followed by grinding using a pin mill, to a size of 250 µm, followed by hydroalcoholic extraction with 60% v / v ethanol, at a rate of 50 g of saffron per liter of hydroalcoholic solution, followed by impregnation on maltodextrin, introduced into the hydroalcoholic solution, and heat treatment in an oven for 48 hours at 40°C.

[0032] Alternatively, the extraction can be an aqueous extraction acidified with hydrochloric acid at pH 4, followed by impregnation onto gum arabic introduced into the aqueous solution, and heat treatment in an oven for 72 hours at 40°C. Other processes are described in patent FR 3054443.

[0033] For the purposes of this invention, "impregnation onto a support" means the addition of a bulking agent to the extraction solution. The support or bulking agent may be chosen from among the following constituents: maltodextrin, sugar, silica, gum arabic, preferably maltodextrin. After this impregnation step, the process may also include an emulsification and / or encapsulation step of the resulting extract. This step consists of high-speed agitation of the extraction solution containing the bulking agent and optionally the processing aid. This agitation may be carried out using processing aids such as gum arabic, cyclodextrins, or fats.

[0034] By "microencapsulation on a support" in the sense of the invention, we mean the insertion of active substances within particles of sizes between Ipm and 1000 pm and more preferably between 30 pm and 500 pm and even more preferably between 50 pm and 300 pm.

[0035] For the purposes of this invention, "carrier" means any food substance of vegetable, mineral or chemical origin used as an ingredient or food additive. A ment allowing the impregnation and thereby the dilution of the extract of the invention. When the extract is impregnated onto a support, the percentages of molecules present in the extract are given by weight of dry matter of the extract including the support.

[0036] By "prevent" or "prevention" in the sense of the invention, we mean the reduction to a lesser degree of the risk or probability of occurrence of a given phenomenon, that is to say, in the context of the present invention, for example, an IBS, a sleep disorder, immunity or stress.

[0037] For the purposes of this invention, "treat" or "treatment" means a reduction in the progression of a disease or disorder, a stabilization, a reversal or regression, or even an interruption or inhibition of the progression of a disease or disorder. In the context of this invention, these terms also apply to one or more symptoms of the diseases or disorders described in this invention.

[0038] IL Composition according to the invention

[0039] The objective of the invention is therefore to provide a composition exhibiting improved efficacy in combating functional bowel disorders, sleep disorders, immunity and stress.

[0040] To this end, the invention relates to a nutritional or therapeutic composition comprising: - at least one plant extract comprising at least 0.2% safranal by weight relative to the total weight of the dry matter, measured by HPLC method and - at least one probiotic bacterium and / or probiotic yeast. The extract integrated into the composition can be derived from (obtained from) any plant containing safranal, in particular Crocus sativus, Centaurea sibthorpii, Centaurea consanguinea, Centaurea amanicola, Erodium cicutarium, Chinese green tea, Caly-c opte ris floribunda, Crocus heuffelianus, Sambucus nigra, Gardenia jasminoides, Citrus silt, Cuminum cyminum L., Achillea distans. Preferably the plant containing safranal from which the extract is obtained is Crocus sativus.

[0042] The extract comprises at least 0.2% safranal by dry weight, measured by HPLC (High-Performance Liquid Chromatography). The measurement method is of utmost importance, given that with another measurement method, particularly UV spectrometry (ISO 3632-2 standard), the result obtained does not correspond to the actual safranal concentration due to the non-specificity of this method.

[0043] The HPLC method of analyzing molecules is a method known to those skilled in the art. It allows for the precise identification and quantification of individual molecules.

[0044] Preferably, the analytical method used to quantify the molecules contained in the extract according to the invention, in particular safranal, is a UHPLC method (Ultra High Performance Liquid Chromatography). This method further increases the resolution and separation of compounds, and allows the detection of multiple compounds on the same chromatogram from a single sample.

[0045] The extract can be obtained by any means that yields at least 0.2% safranal by weight of dry matter of the extract. Preferably, the extract can be prepared according to the extraction process described in patent FR 3054443.

[0046] Preferably, the extract incorporated into the composition comprises crocins and / or flavonoids derived from kaempferol and / or derivatives of picrocrocin.

[0047] Crocetin and its derivatives such as crocin, aglycone and / or glycosylated crocetins can, as before, be extracted from Crocus sativus or Gardenia jasminoides and is mainly responsible for the color of saffron.

[0048] In a particularly preferred manner, the extract of Crocus sativus comprises terpenes such as safranal. Terpenes are volatile active compounds contained in saffron and are known from the prior art to have antimicrobial activity and thus an action against bacteria. For example, the article by Nanasombat et al. 2014 describes the inhibition of two strains of Lactobacillus iplantarum and casei and one strain of Saccharomyces cerevisiae with saffron pollen, in particular with safranal and crocins. The article by Liu et al. 2017 describes such an interaction between safranal and a strain of Escherichia coli. The article by Nadir et al. 2019 describes the effects of terpenes on Staphylococcus aureus, Bacillus cereus, Entorococcus faecalis, Salmonella typhi, Pseudomonas aeruginosa, E. coli strains. More recently, the article by Ambrosio et al. 2020 describes the effect of terpenes on E. coli and Eactobacillus rhamnosus strains.

[0049] Surprisingly, the specific combination and quantity of molecules in the present composition makes it possible to obtain an effect on IBS, sleep disorders, immunity and stress in humans or animals, this effect being better than that of a saffron extract alone or a probiotic bacterium or yeast alone.

[0050] Preferably, the quantity of plant extract by weight in relation to the total weight of dry matter is between 0.5% and 20% and the quantity of probiotic bacteria and / or probiotic yeast is between 80% and 99.5%.

[0051] Preferably, the extract may comprise, by weight of dry matter of the extract, measured by HPLC, at least 1% of crocins and / or at least 500ppm of kaempferol-derived flavonoids and / or at least 0.5% of picrocrocin derivatives.

[0052] In the context of the invention, the extract according to any of the preceding embodiments is integrated into the composition and associated with at least one probiotic bacterium and / or probiotic yeast or a mixture.

[0053] Preferably, the probiotic bacterium and / or probiotic yeast may be dead, inactivated, semi-inactivated, or live. Said bacterium or yeast is preferably chosen from bacteria or yeasts of the genera Lactobacillus, Bifidobacterium, Streptococcus, Saccharomyces, Enterococcus, Pediococcus and Escherichia. Even more preferably, the strain is chosen from Eactobacillus, Bifidobacterium, and their mixture.

[0054] Preferably, the bacterium is chosen from bacteria of the following species: Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus delbrueckii ssp bulgaricus, Lactobacillus casei, Lactobacillus brevis, Lactobacillus fermentum, Lactobacillus reuteri, Lactobacillus salivarius, Lactobacillus paracasei, Lactobacillus helveticus, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium coagulons, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium brevis, Bifidobacterium bifium, Lactococcus lactis, Streptococcus thermophilus, Streptococcus thermophiles, Streptococcus faecium, Enterococcus Eaecalis, Enterococcus faecium Escherichia coli, Pediococcus acidilactici, Bacillus coagulans, Bacillus subtillis and their mixtures.

[0055] Preferably, the yeast is chosen from yeasts of the following species: Saccharomyces cerevisiae, Saccharomyces boulardii and their mixtures.

[0056] When the composition is intended to be used to improve digestion, the strain is chosen from bacteria and yeasts of the following species: Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus delbrueckii ssp bulgaricus, Lactobacillus casei, Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium bifium, Bifidobacterium breve, Pediococcus acidilactici, Streptococcus thermophilus, Saccharomyces cerevisiae, Streptococcus faecium, Enterococcus eaecalis, Enterococcus faecium, Escherichia coli and mixtures thereof.

[0057] When the composition is intended to be used to improve sleep, the strain is chosen from bacteria of the following species: Lactobacillus fermentum, Lactobacillus rhamnosus, Lactobacillus plantarum, Bifidobacterium longum, Lactobacillus brevis, Lactobacillus casei, Lactobacillus helveticus and mixtures thereof.

[0058] When Bifidobacterium longum is combined with Lactobacillus acidophilus, the composition is preferentially intended for use in improving digestion.

[0059] According to a particular embodiment, the composition according to the invention provides daily between 1105 and 91012 CFU, preferably between 1107 and 910 of a probiotic bacterium and / or yeast and / or a mixture

[0060] According to another embodiment, the composition may also include at least one vitamin selected from vitamins A, Bl, B2, B3, B3 / PP, B5, B6, B8 / H, B9, B12, C, D, E, K and their mixture.

[0061] The composition may also include at least one mineral selected from Calcium, Iodine, Zinc, Magnesium, Copper, Iron, Selenium, Potassium, the Fluoride, Manganese, Chloride, Chromium, Phosphorus and their mixtures and / or at least one amino acid derivative selected from Creatine, Betaine and their mixtures.

[0062] The composition may also include at least one prebiotic and / or starch and / or at least one polyphenol in addition to those present in the plant extract(s).

[0063] Preferably, the prebiotics are chosen from FOS, GOS and the polyphenols are derived from red fruits, cocoa flavanols, olive oil or grapes.

[0064] According to another embodiment, the composition also includes lipids, such as phytosterols, omega 6 and omega 3; alpha-cyclodextrin, prunes, beta-glucan, lactulose, lactase, guar gum, melatonin, nuts, proteins, chitosan, red yeast rice or charcoal.

[0065] When the composition is intended to be used to improve digestion, the composition may include fibers selected from wheat, oats, barley, rye, beet fibers, konjac, pectins and chicory inulin.

[0066] Preferably, the amount of fiber provided is between 3g per 100g of composition and 6g per 100g of composition and / or it is between 1.5g per 100kcal of composition and 3g per 100kcal of composition.

[0067] The composition according to the invention or the plant extract can also be impregnated onto a support and / or microencapsulated in a support.

[0068] Microencapsulation is particularly advantageous and makes it possible to stabilize and protect the saffron extract from its environment, especially from the organism. Thus, terpenes such as safranal and saffron carotenoids such as crocins and / or pricocrocins are protected.

[0069] Furthermore, microencapsulation allows for the encapsulation of volatile and heat-sensitive active metabolites within the matrix, thus enabling the production of a saffron extract with a high concentration of active compounds. Finally, microencapsulation improves the stability, bioavailability, and usability of the extract in food matrices, notably by masking the taste and increasing resistance to potential alterations of the compounds during the food production process.

[0070] Thus, according to a first embodiment, the composition or plant extract is microencapsulated in a food carrier selected from maltodextrin, gum arabic, hydrogenated or non-hydrogenated oil, wax, alginates, and starch and protein. Such a microencapsulation process is well known to those skilled in the art.

[0071] According to a second embodiment, the composition or plant extract is impregnated onto a support, preferably a food-grade support. Such a process for impregnating the support is described in French patent FR 3054443. The impregnation step consists of adding a bulking agent to the extraction solution. The support or bulking agent may, in particular, be chosen from among the constituents include: maltodextrin, sugar, silica, gum arabic, preferably maltodextrin.

[0072] According to a third embodiment, the composition or plant extract is impregnated onto a food support and then the composition or plant extract is semi-encapsulated in a food support chosen from maltodextrin, gum arabic, hydrogenated or non-hydrogenated oil, a wax, alginates and starch and protein.

[0073] The composition can also be incorporated into a food supplement in the form of a capsule, powder, tablet, solution, or chewing gum. Preferably, the plant extract is microencapsulated before being incorporated into the food supplement. Thus, the invention also relates to a composition characterized in that it is a food supplement in the form of a capsule, powder, tablet, solution, or chewing gum.

[0074] According to another embodiment, the composition according to the invention can be incorporated into a food product selected from dairy products, cereals, cereal products, and beverages. Thus, the invention also relates to a composition characterized in that it is a food product selected from dairy products, cereals, cereal products, and beverages.

[0075] III. Use of a composition according to the invention / Composition for its use

[0076] The composition according to the invention is intended to prevent and / or combat stress, mood disorders, sleep disorders, digestive disorders, immune disorders, vision disorders, erectile dysfunction, female libido disorders, joint disorders, cognitive disorders, cardiovascular disorders, disorders related to premenstrual syndrome, disorders related to menopause, or to prevent and combat weight gain. Thus, the invention relates to the composition as described above for these uses.

[0077] The composition according to the invention also makes it possible to improve and strengthen the immune system, recovery, sports performance, and oral health.

[0078] The composition can also be used for its anti-aging properties, particularly on the skin and in sun protection.

[0079] Preferably, mood disorders are chosen from depression, bipolar disorder and dysthymia.

[0080] Preferably, stress-related disorders are chosen from generalized anxiety disorder, panic disorder, social anxiety disorder, specific phobia, obsessive-compulsive disorder, post-traumatic stress disorder.

[0081] Preferably, cognitive disorders are chosen from Alzheimer's disease and / or Parkinson's disease and / or Huntington's disease and / or dementia cognitive pathology and / or dementia and / or depression and / or schizophrenia and / or mental retardation and / or disorders related to post-menopausal state in women and / or cognitive dysfunction syndrome (CDS).

[0082] Preferably, digestive disorders are chosen from irritable bowel syndrome, Crohn's disease, ulcerative colitis, celiac disease, Whipple's disease, ulcerative colitis, dyspepsia, intestinal occlusions and intestinal transit.

[0083] Preferably, vision disorders are chosen from age-related macular degeneration, glaucoma, diabetic retinopathy.

[0084] The composition according to the invention is also intended for non-therapeutic use to combat stress, mood disorders, sleep disorders, digestive disorders, immune disorders, vision disorders, erectile dysfunction, female libido disorders, joint disorders, cognitive disorders, cardiovascular disorders, disorders related to premenstrual syndrome, disorders related to menopause, or to prevent and combat weight gain in humans or animals, to improve and strengthen the immune system, recovery, athletic performance, as well as oral health, and for its anti-aging properties, particularly on the skin and in sun protection in healthy humans or animals, i.e., those not suffering from illness. Thus, the invention relates to these non-therapeutic uses of the composition as described above.

[0085] The invention is now illustrated by examples of composition according to the invention and a test result demonstrating the absence of antimicrobial activity of safranal.

[0086] IV. Example

[0087] Example of a composition intended for human use.

[0088] Examples of composition according to the invention are presented in Table 1 below.

[0089] [Tables 1] Ingredients Example 1 - Example 2 - Sleep Example 3 - Digestion Stress Saffron extract 30mg 60mg 30mg Probiotics Lactobacillus aci-dophilus Lactobacillus fermentum X Bifidobacterium lactis XX Bifidobacterium longum XX Bifidobacterium bifidum Vitamins Vitamin A Vitamin B3 2.4 mg Vitamin B12 0.375 pg 0.375 pg Minerals Magnesium 56.25 mg Calcium 120 mg Fiber Barley 3000 mg Other Melatonin 1 mg Activated Charcoal 1000 mg TOTAL 245.3 mg 2561 mg 4327 mg Dosage Form Capsule Sachet Powder

[0090] Example 1 comprises 30 mg of a saffron extract and 159 mg of a mixture of 11 probiotic bacterial strains in capsule form. The composition according to Example 1 is obtained by mixing the constituents under conventional conditions known to those skilled in the art.

[0091] Example 2 comprises 60 mg of a saffron extract and 2,500 mg of a mixture of 4 probiotic bacterial strains in powder form contained in a sachet. The composition according to Example 2 is obtained by mixing the constituents under conventional conditions known to those skilled in the art.

[0092] Example 3 comprises 30 mg of probiotic and 175 mg of a mixture of 6 probiotic bacterial strains in powder form. The composition according to Example 3 is obtained by mixing the constituents under conventional conditions known to those skilled in the art.

[0093] The composition examples are obtained by mixing the constituents under the classic conditions known to a person skilled in the art.

[0094] IV. Evaluation of the effect of the composition

[0095] The composition according to the invention demonstrated the stability of probiotic bacteria after incubation for 48 hours at 37°C in contact with the plant extract comprising at least 0.2% safranal, as measured by HPLC. The composition according to the invention thus inhibits the natural antibacterial activity of safranal.

Claims

Demands

1. Nutritional or pharmaceutical composition comprising: - at least one plant extract comprising at least 0.2% of safranal by weight relative to the total weight of dry matter, measured by HPLC method, and - at least one probiotic bacterium and / or probiotic yeast.

2. Composition according to the preceding claim, characterized in that the plant extract is an extract of Crocus sativus.

3. Composition according to any one of the preceding claims, characterized in that the extract of Crocus sativus comprises crocins and / or flavonoids derived from kaempferol and / or derivatives of picrocrocin.

4. Composition according to the preceding claim, characterized in that the extract of Crocus sativus comprises terpenes.

5. Composition according to the preceding claim, characterized in that the extract comprises, by weight of dry matter of the extract, measured by HPLC, at least 1% of crocins and / or at least 500ppm of kaempferol-derived flavonoids and / or at least 0.5% of picrocrocin derivatives.

6. Composition according to any one of the preceding claims, characterized in that the probiotic bacterium and / or probiotic yeast is dead, inactivated, semi-inactivated or alive.

7. Composition according to any one of the preceding claims, characterized in that the probiotic bacterium and / or probiotic yeast is selected from bacteria and / or yeast of the genera Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Saccharomyces, Enterococcus, Pediococcus and Es-cherichia.

8. Composition according to any one of the preceding claims, characterized in that the extract of Crocus sativus is obtained from stigmas and / or petals and / or bulbs of Crocus sativus.

9. Composition according to any one of the preceding claims, characterized in that it also comprises at least one vitamin selected from vitamins A, B1, B2, B3, B3 / PP, B5, B6, B8 / H, B9, B12, C, D, E and K.

10. A composition according to any one of the preceding claims, characterized in that it also comprises at least one mineral selected from Calcium, Iodine, Zinc, Magnesium, Copper, Iron, Selenium, Potassium, Fluorine, Manganese, Chloride, Chromium and Phosphorus and / or at least one amino acid derivative selected from the Creatine and Betaine.

11. Composition according to any one of the preceding claims, characterized in that it also comprises at least one prebiotic and / or starch and / or at least one polyphenol in addition to those present in the plant extract(s).

12. Composition according to the preceding claim, characterized in that the prebiotics are selected from FOS, GOS and polyphenols in addition to those present in the plant extract(s) from red fruits.

13. Composition according to any one of the preceding claims, characterized in that the composition or plant extract is impregnated onto a support and / or microencapsulated in a food support selected from maltodextrin, gum arabic, hydrogenated or non-hydrogenated oil, wax, alginates, and starch and protein.

14. Composition according to any one of the preceding claims, characterized in that the composition is a food supplement in the form of a capsule, powder, tablet, solution or chewing gum.

15. Composition according to any one of claims 1 to 13, characterized in that the composition is a food product in the form of dairy products, cereals, cereal products and beverages.

16. Composition according to any one of the preceding claims, for use in the prevention and / or treatment of digestive disorders, sleep disorders, immune disorders, vision disorders, mood disorders, erectile dysfunction, female libido disorders, joint disorders, cognitive disorders, cardiovascular disorders, premenstrual disorders, menopausal disorders, stress-related disorders, to facilitate weight loss, to provide anti-aging action, particularly on the skin and sun protection, in humans or animals.

17. Composition according to the preceding claim, for its use in the prevention and / or treatment of digestive disorders selected from irritable bowel syndrome, Crohn's disease, ulcerative colitis, celiac disease, Whipple's disease, ulcerative colitis, dyspepsia, intestinal occlusions and intestinal transit.

18. Composition for its use according to claim 17, characterized in that it also comprises fibers selected from wheat, oats, barley or rye.