AU2021107611A4

AU2021107611A4 - Composition comprising a mixture of vitis vinifera and vaccinium angustifloium extracts and probiotics for improving cognitive functions

Info

Publication number: AU2021107611A4
Application number: AU2021107611A
Authority: AU
Inventors: Séverine DUBREUIL; David Gaudout; Benoît LEMAIRE; Camille POUCHIEU; Stéphane REY
Original assignee: Activinside SAS
Current assignee: Activinside SAS
Priority date: 2020-07-24
Filing date: 2021-07-26
Publication date: 2022-01-06
Anticipated expiration: 2029-07-26
Also published as: WO2022018281A2; PL438609A1; WO2022018281A3; FR3112686B3; FR3112686A3; DK202100060U3

Abstract

The present invention relates to a nutritional or pharmaceutical composition comprising at least one mixture of extracts of Vitis vinifera and Vaccinium angustifolium, and at least one probiotic bacterium and/or probiotic yeast. Such a composition is intended to be used as a 5 nutritional product or drug to improve cognitive functions in humans or animals.

Description

Composition comprising a mixture of Vitis vinifera and Vaccinium angustifolium extracts and probiotics for improving cognitive functions

[0001] Technical area

[0002] The invention concerns a composition comprising at least one mixture of extracts of Vitis vinfera and Vaccinium angustifolium, and at least one probiotic bacterium and/or probiotic yeast. Such a composition is intended to be used as a nutritional product or medicine

for improving cognitive functions in humans or animals.

[0003] Earlier art

[0004] Cognitive decline and the appearance of the first cognitive disorders, in particular neurodegenerative diseases such as Alzheimer's or Parkinson's disease, mainly affect elderly

subjects. Due to the evolution of medicine and the quality of care provided, the elderly

population is increasing. There is therefore a high prevalence of these age-related pathologies. It is therefore of interest to develop solutions to prevent or minimize age-related cognitive

decline and delay the onset of associated pathologies, in particular to prolong the autonomy of the elderly population and thus maintain their quality of life.

[0005] Healthy subjects with no pathology are also looking for solutions to improve their cognitive functions, in particular memory, attention, concentration, alertness, learning,

language, mood, stress, anxiety or sleep and thus maintain a state of well-being. It is known

that nutrition is an important factor in preventing the alteration of cognitive functions.

[0006] For this purpose, nutritional agents and food supplements have been developed. In

particular, patent FR3042712 describes a mixture of molecules obtained from Vitis vinifera and Vaccinium angustifolium, comprising at least 1% of catechin and/or epicatechin, and at least 5

ppm of ferulic acid. Two clinical studies showing the effectiveness of this mixture of molecules have been published (Bensalem J et al. Polyphenols From Grape and Blueberry Improve

Episodic Memory in Healthy Elderly with Lower Level of Memory Performance: A Bicentric Double-Blind, Randomized, Placebo-Controlled Clinical Study. J Gerontol A Biol Sci Med Sci.

2019 Jul 19;74(7):996-1007; Hakkinen PJ. Hair. In: Editor-in-Chief: Philip W, editor. Encyclopedia of Toxicology (Second Edition). New York: Elsevier; 2005. p. 475-7). Such a mixture is thus

known as well as its effects on the cognitive functions of the human being at the time of acute catch in the young adult or chronic catch in the old person.

[0007] It is also commonly accepted that the intestinal tract of humans and animals harbors a large number of diverse microbial populations, called microbiota and zoobiota respectively.

More and more studies confirm the importance of the gut microbiota for host health, including

cognitive and psychological functions through the bidirectional gut-brain axis (Tyler Patterson T, Grandhi R. Gut Microbiota and Neurologic Diseases and Injuries. In: Advances in Experimen

tal Medicine and Biology. Springer; 2020. p. 73-91). Dysbiosis of the gut microbiota may be associated with behavioral and cognitive disorders.

[0008] Furthermore, intestinal inflammation may promote cognitive impairment and dementia. For example, a decrease in the abundance of anti-inflammatory bacterial species

such as Bifidobacterium breve strain Al and an increase in the abundance of pro-inflammatory flora phyla such as Firmicutes and Bacteroidetes are the most distinct alterations in the gut

microbiota of Alzheimer's disease patients.

[0009] Modulating the gut microbiota to improve cognitive function and prevent dementia is therefore a very promising preventive or therapeutic approach. Dietary modifications,

including prebiotic and probiotic supplementation, have been shown to improve the

composition of the intestinal microbiota and thus have a positive effect on cognitive function.

[0010] Probiotics are living microorganisms that confer a health benefit on the host when provided in sufficient quantities. Prior art teaches us that taking probiotics can effectively act

on the cognitive functions of the animal (Wang H, Lee IS, Braun C, EnckP. Effect of probiotics on central nervous system functions in animals and humans: A systematic review. Vol. 22,

Journal of Neurogastroenterology and Motility. Journal of Neurogastroenterology and Motility; 2016. p. 589-605). It is also known from the prior art that the use of probiotics of the same or different species improved cognitive function in subjects with mild cognitive impairment or

Alzheimer's disease, possibly by reducing inflammation and oxidative stress (Deng H, et al. Efficacy of probiotics on cognition, and biomarkers of inflammation and oxidative stress in

adults with Alzheimer's disease or mild cognitive impairment-A meta-analysis of randomized controlled trials. Vol. 12, Aging. Impact Journals LLC; 2020. p. 4010-39; Akbari E, et al. Effect of

probiotic supplementation on cognitive function and metabolic status in Alzheimer's disease: A randomized, double-blind and controlled trial. Front Aging Neurosci. 2016 Nov

10;8(NOV):256; Kobayashi Y, et al. Effects of bifidobacterium breve al on the cognitive function

of older adults with memory complaints: A randomised, double-blind, placebo-controlled trial. Benef Microbes. 2019; 10(5):511-20).

[0011] Thus, it is already known from the prior art that nutritional agents comprising a mixture of Vitis vinifera and Vaccinium angustifolium extracts or probiotics taken individually to improve cognitive functions in humans or animals.

[0012] However, there is still a need for a new solution with improved efficacy compared to the prior art to prevent and/or treat cognitive decline as part of the normal aging process or to slow the progression of dementia or to maintain a stable or improved cognitive state for a healthy subject not suffering from any pathology associated with cognitive decline.

[0013] Summary of the invention

[0014] To meet this need, the present invention proposes a new composition comprising at least one mixture of extracts of Vitis vinifera and Vaccinium angustifolium, and at least one probiotic bacterium and/or probiotic yeast.

[0015] Such a composition is not known in the prior art. However, the combination of a mixture of extracts of Vitis vinifera and Vaccinium angustifolium and at least one probiotic bacterium and/or probiotic yeast is particularly advantageous. Such a combination makes it possible to obtain a synergistic effect, in particular a prebiotic effect due to the polyphenols, in order to improve cognitive functions compared to a mixture of the said extract or a probiotic consumed individually by humans or animals. In addition, polyphenols are known to have antimicrobial activity. However, unexpectedly, the combination of polyphenols provided concomitantly by extracts of Vitis vinifera and Vaccinium angustifolium do not show such effects on the probiotics of the invention.

[0016] To this end, the invention provides a novel nutritional or pharmaceutical composition comprising: at least one mixture of extracts of Vitis vinifera and Vaccinium angustifolium, and at least one probiotic bacterium and/or probiotic yeast.

[0017] The probiotic bacteria and/or probiotic yeast incorporated in the composition according to the invention is preferably selected from bacteria and/or yeasts of the genus Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Saccharomyces, Enterococcus, Pediococcus and Escherichia.

[0018] Such a composition is particularly intended to be administered in humans or animals as a drug to prevent and/or treat pathologies associated with cognitive decline but also as a nutritional product to prevent and/or treat normal cognitive decline in a healthy subject.

[0019] Thus, the composition is also intended for healthy subjects without pathologies associated with cognitive decline.

[0020] Another object of the invention thus relates to a non-therapeutic use of the

composition according to the invention in humans or healthy animals, to improve cognitive

functions and/or executive functions, and/or to limit normal age-related cognitive decline.

[0021] Further features and advantages will be apparent from the detailed description of the

invention and the examples that follow.

[0022] Detailed description of the invention

[0023] Definition

[0024] By "nutritional composition" is meant, within the meaning of the invention, any

mixture of food compounds intended to be ingested by a healthy subject and comprising a o mixture of extracts of Vitis vinifera and Vaccinium angustifolium and at least one probiotic

bacterium and/or probiotic yeast. The nutritional compositions are in particular food

compositions or foods, or food supplements.

[0025] By "healthy subject", we mean a subject who can be a human or an animal not suffering

from any pathology associated with pathological cognitive decline such as Alzheimer's disease,

Parkinson's disease, Huntington's disease, motor neuron disease or age-related macular degeneration (AMD).

[0026] Conversely, by "pathological subject", we mean a subject who suffers or is likely to

suffer from pathological cognitive decline such as Alzheimer's disease, Parkinson's disease, Huntington's disease, motor neuron disease or age-related macular degeneration (AMD).

[0027] By "pharmaceutical composition" is meant, within the meaning of the invention, any composition comprising at least one active substance presented as having curative or preventive properties with respect to human or animal diseases, used alone or in combination

with other active or non-active substances and intended to be ingested by a pathological subject. Such a composition comprises in particular a mixture of extracts of Vitis vinifera and

Vaccinium angustifolium and at least one probiotic bacterium and/or probiotic yeast. The pharmaceutical composition is thus a drug intended for humans or animals in the prevention

and/or treatment of pathological cognitive decline such as Alzheimer's disease, Parkinson's disease, Huntington's disease, motor neuron diseases or age-related macular degeneration

(AMD).

[0028] By "a mixture of Vitis vinifera and Vaccinium angustifolium extracts" is meant a set of molecules obtained from a mixture of Vitis vinifera and Vaccinium angustifolium, preferably a

mixture of at least one Vitis vinifera extract and at least one Vaccinium angustifolium extract

The raw material of Vitis vinifera can be the leaves and/or fruits and/or seeds and/or woods,

preferably the raw material of Vitis vinifera is the aerial part of the plant, i.e. all the leaves,

fruits, skin (pellicle), seeds and woods, more preferably the skin (pellicle) and the seeds. The raw material of Vaccinium angustifolium can be the leaves and/or the fruits, preferably the

raw material of Vaccinium angustifolium is the whole leaves and fruits of the plant.

[0029] By "at least X% catechins and/or epicatechins" is meant either at least X% catechins if

there are no epicatechins in the mixture, or at least X% epicatechins if there are no catechins in the mixture, or at least X% of the mixture of catechins and epicatechins if both catechins

and epicatechins are present in the mixture. Preferably, this means at least X% of the mixture of catechins and epicatechins.

[0030] The term "ppm" refers to parts per million (mg/kg) in the mixture. Unless otherwise

specified, ppm refers to weight in relation to the total weight of the mixture.

[0031] By "prevent" or "prevention" in the sense of the invention is meant the reduction to a

lesser degree of the risk or probability of occurrence of a given phenomenon, i.e., in the

context of the present invention, for example, a pathological cognitive disorder.

[0032] By "treat" or "treatment" within the meaning of the invention, it is meant a decrease in the progression of the disease or disorder, a stabilization, reversal or regression, or even an

interruption or inhibition of the progression of a disease or disorder. In the context of the invention, these terms also apply to one or more symptoms of said diseases or disorders of

the present invention.

[0033] Composition

[0034] The objective of the invention is therefore to provide a composition with improved

efficacy in combating cognitive decline.

[0035] To this end, it is therefore an object of the present invention to provide a nutritional or

pharmaceutical composition comprising: at least one mixture of extracts of Vitis vinifera and Vaccinium angustifolium, and

at least one probiotic bacterium and/or probiotic yeast.

[0036] The extract according to the invention can be obtained by any process for obtaining a

mixture of Vitis vinifera and Vaccinium angustifolium extracts and will be detailed hereinafter

in this description.

[0037] Preferably, the extract mixture comprises a mixture of molecules comprising: - at least 1% of catechins and/or epicatechins, the percentage being given by weight with respect to the total weight of the mixture, and - at least 5 ppm ferulic acid.

[0038] Catechins and epicatechins are compounds of the flavonoid family, in particular of the flavanol subclass. They are also known as catechol and epicatechol and are powerful

antioxidants that help prevent inflammatory and coronary diseases but also maintain or increase cognitive performance.

[0039] Ferulic acid is known for its effects on the neuronal system, in particular for protecting neuronal cells from cell death induced by cerebral ischemia (Cheng S.Y, et al. Ferulic acid

provides neuroprotection against oxidative stress-related apoptosis after cerebral ischemia/reperfusion injury by inhibiting ICAM-1 mRNA expression in rats. Brain Res.

2008;1209:136-150). Moreover, its antioxidant activity has been tested in Alzheimer's disease

(Sgarbossa A, et al. Ferulic Acid: A Hope for Alzheimer's Disease Therapy from Plants. Nutrients. 2015;7(7):5764-82.) and its long-term administration appears to protect against memory and

learning deficits (Yan J.Y. et al. Protection against p-amyloid peptide toxicity in vivo with long term administration of ferulic acid. Br J Pharmacol. 2001;133:89-96.).

[0040] The effect of the composition is particularly increased and effective when it also includes: - at least 200 ppm resveratrol, and/or - at least 50 ppm of quercetins and/or quercetin glycosides and/or

- at least 500 ppm of anthocyanins.

[0041] Resveratrol is particularly known to be present in grapes. However, it can also be derived from other plant sources, in particular from Polygonum cuspidatum, but also through

biotechnology. It has many beneficial activities for humans and animals, including an improvement in working memory, learning, spatial memory and spontaneous motor activity

(Abraham J, Johnson RW. Consuming a diet supplemented with resveratrol reduced infection related neuroinflammation and deficits in working memory in aged mice. Rejuvenation Res

[Internet]. 2010/01/01. 2009;12(6):445-53).

[0042] Quercetin also has significant neuroprotective activity (Dajas F, et al. Neuroprotective

actions of flavones and flavonols: mechanisms and relationship to flavonoid structural features.

Cent Nerv Syst Agents Med Chem. 2013; 13(1):30-5).

[0043] It is also known that the consumption of foods rich in anthocyanidins (aglycones and/or

glycosylated) prevents memory deficits and improves cognitive performance (Barros D, et al.

Behavioral and genoprotective effects of Vaccinium berries intake in mice. Pharmacol Biochem

Behav.2006; 84(2):229-34).

[0044] The composition according to the invention comprises at least one probiotic bacterium and/or probiotic yeast associated with the extract mixture.

[0045] Surprisingly, the specific combination as well as the quantity of the molecules found in the present composition makes it possible to obtain an effect on cognitive decline in humans

or animals, this effect being better than that of an extract of Vitis vinifera and Vaccinium angustifolium alone or of at least one probiotic bacterium and/or probiotic yeast alone.

[0046] Preferably, the probiotic bacteria and/or probiotic yeast can be dead, inactivated, semi inactivated or alive.

[0047] Said probiotic bacteria and/or yeast preferably belongs to the genus Lactobacillus,

Bifidobacterium, Bacillus, Streptococcus, Saccharomyces, Enterococcus, Clostridium, Lactococcus and Escherichia.

[0048] Particularly preferred, the mixture, the probiotic bacteria and/or yeast is selected from

bacteria and/or yeast of the genus Lactobacillus, Bifidobacterium, Streptococcus, Enterococcus and Lactococcus.

[0049] Preferably, the bacteria is selected from the following species: Lactobacillus plantarum,

Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus delbrueckii ssp delbrueckii, Lactobacillus casei, Lactobacillus casei Shirota, Lactobacillus

curvatus Lactobacillus brevis, Lactobacillusfermentum, Lactobacillus salivarius, Lactobacillus mucosae, Lactobacillus paracasei, Lactobacillus johnsonii, Lactobacillus pentosus, Lactobacillus helveticus, Bifidobacterium bifidum , Bifidobacterium infantis, Bifidobacterium

lactis, Bifidobacterium longum, Bifidobacterium longum spp infantis, Bifidobacterium longum spp longum, Bifidobacterium animals spp lactis, Bifidobacterium adolescentis,

Bifidobacterium breve, Lactococcus lactis, Lactococcus lactis spp lactis, Streptococcus thermophilus, Streptococcus thermophiles, Clostridium butyricum, Enterococus faecalis, and

their mixtures.

[0050] Preferably, the yeast is selected from the yeasts of the following species:

Saccharomyces cerevisiae, Saccharomyces boulardii and their mixture.

[0051] According to a particular embodiment, the composition according to the invention provides daily between 1x105 and 9x1012 CFU, preferably between 1x107 and 9x1011 of a

probiotic bacterium and/or yeast and/or a mixture.

[0052] The composition may also include at least one prebiotic selected from inulin, oligosaccharides, FOS (fructo-oligosaccharides), GOS (galacto-oligosaccharides), CLA

(conjugated linoleic acid), PUFA (polyunsaturated fatty acid), MOS (mannanoligosaccharide) and XOS (xylooligosaccharide).

[0053] The addition of prebiotic enhances the effectiveness of the composition. When associated, mixed, combined with an extract of Vitis vinifera and Vaccinium angustifolium and

at least one probiotic, the composition has an improved effect in the prevention and/or treatment of cognitive decline.

[0054] According to another object, the composition can be encapsulated or microencapsulated, preferably the composition is encapsulated or microencapsulated in a

food carrier selected from maltodextrin, gum arabic, hydrogenated or non hydrogenated oil,

wax, alginates, starch, hydrolyzed or non-hydrolyzed proteins, phosphatidylcholine, phospholipids, galactomannan, emulsifiers selected from pectin or polyglycerol

polyricinoleate and fibers selected from polydextrose, HPMC and cellulose.

[0055] The encapsulation is particularly advantageous and allows to stabilize and protect the Vitis vinifera and Vaccinium angustifolium extract and/or the probiotic(s) (bacteria and/or yeast) from its environment, in particular from the body.

[0056] Furthermore, the encapsulation allows for improved stability, bioavailability and use of said extract in food matrices, including taste masking and resistance to possible alterations of

the compounds during the production steps of a food product.

[0057] Microencapsulation provides the same advantages as encapsulation, but particularly allows the insertion of active substances within particles of sizes between 1 pm and 1000 pm

and more preferably between 30 pm and 500 pm and even more preferably between 50 pm and 300 jm.

[0058] The composition according to the invention is intended to be administered as a nutritive or therapeutic product and can therefore be presented in different forms, preferably

in the form of a powder, capsule, tablet, solution, suspension, emulsion or chewing gum.

[0059] When the composition is intended to be administered as a nutritional product, it may

be in the form of a food product, preferably in the form of dairy products, purees, cereals,

grain products and beverages.

[0060] When the composition is administered as a therapeutic product, the invention relates

to a composition for use as a human or animal drug.

[0061] Cognitive decline is characterized by an age-related decline in cognitive and executive

functions, particularly concentration, working memory, long-term memory, reasoning,

judgment, problem solving, and information processing speed. These impairments can lead to a decrease in self-esteem and quality of life. Age-related cognitive decline is the term used to

describe the non-pathological form of deterioration of memory and cognitive function that occurs as a result of the aging process within the normal range for a person's age. It is a

complex process, with the first signs emerging in humans between 35 and 65 years of age, without specific neurodegenerative lesions. Progressive cognitive decline is noticeable by the

appearance of minor cognitive problems that affect 15 to 20% of the population aged 65 or more, but which represent an unstable state. However, certain pathological forms can occur

in addition to this "normal" cognitive decline. Among these pathologies, Alzheimer's disease

is the most common cause of dementia, affecting over 24 million people worldwide. It is irreversible in our current state of knowledge, the only available treatments being purely

symptomatic. In animals, these pathologies can present themselves in a very similar way. In

dogs, for example, cognitive dysfunction syndrome (or CDS) is a widespread pathology characterized by spatio-temporal disorientation, loss of basic learning skills that often leads to uncleanliness, altered sleep-wake cycles, and impaired social interactions.

[0062] In particular, the composition is intended to be used in neuroprotection, and/or improvement of cognitive functions and/or memory and/or executive functions, and/or

mitigation of cognitive decline. Thus, the composition according to the invention exhibits neuroprotective effects and may be used in the prevention and/or treatment of pathologies associated with cognitive decline.

[0063] Preferably, the composition according to the invention can be used in the prevention and/or treatment of pathologies associated with the destruction of neurons, the decrease in

cognitive functions, memory, executive functions.

[0064] The composition according to the invention is particularly intended to be used in the

prevention and/or treatment of: - neurodegenerative diseases such as Alzheimer's disease, and/or Parkinson's disease,

and/or Huntington's disease, and/or motor neuron disease and/or age-related

macular degeneration (AMD), - pathological cognitive decline and/or dementia and/or depression and/or anxiety

and/or schizophrenia and/or mental retardation and/or cognitive dysfunction syndrome (CDS).

[0065] According to a particularly advantageous mode, the composition according to the

invention is delivered at a dose to provide the human or animal : - at least 100 pg per kg of body weight of catechins and/or epicatechins,

- at least 0.05 pg per kg of body weight of ferulic acid.

[0066] Preferably, said composition according to the invention is delivered at a dose to provide

the human or animal : - at least 10 pg per kg of body weight of resveratrol,

- at least 0.2 pg per kg body weight of quercetin and/or quercetin glycosides, and

- at least 1 pg per kg of body weight of anthocyanidins.

[0067] According to another aspect, it may also be a nutritional or therapeutic composition

intended for the animal. By "animal" is meant any animal that can receive a nutritional or therapeutic composition according to the invention, for example but not limited to a pet

animal, a poultry, a pig, a ruminant, a goat, or a mouse. Preferably, the animal is a pet, such as

a cat or dog. Even more preferably, the animal is a dog.

[0068] Non-therapeutic use in a healthy person

[0069] According to another aspect, the composition according to the invention is also

intended to be used as a nutritive product without any therapeutic effect and in a healthy

subject.

[0070] Thus, the invention also relates to a non-therapeutic use of the composition according to the invention in humans or healthy animals, to improve cognitive functions and/or executive functions, and/or to limit normal age-related cognitive decline.

[0071] Particularly preferably, the invention relates to a non-therapeutic use of the composition for improving memory and/or attention and/or concentration and/or alertness

and/or learning and/or intelligence and/or language and/or mood and/or stress and/or anxiety and/or sleep.

[0072] The composition according to the invention in non-therapeutic use may be preferentially delivered in an amount to provide a healthy human or animal: - at least 100 pg per kg of body weight of catechins and/or epicatechins,

- at least 0.05 pg per kg of body weight of ferulic acid.

[0073] Preferably, said composition according to the invention is delivered in an amount to

provide the healthy human or animal :

- at least 10 Ig per kg of body weight of resveratrol, - at least 0.2 pg per kg body weight of quercetin and/or quercetin glycosides, and

- at least 1 pg per kg of body weight of anthocyanidins.

[0074] Process

[0075] The process according to the invention makes it possible to obtain an extract mixture comprising the following mixture of molecules: - at least 1% of catechin and/or epicatechin by weight with respect to the total weight

of the mixture, preferably at least 5%, even more preferably between 5% and 50%,

especially between 7% and 35%,

- at least 5 ppm of ferulic acid, preferably at least 10 ppm, even more preferably between 5 and 300 ppm, especially between 10 and 100 ppm.

[0076] In a particularly preferred way the process allows to obtain a mixture of molecules comprising : - at least 200 ppm of resveratrol, preferably at least 300 ppm, even more preferably

at least 400 ppm, - at least 50 ppm of quercetin and/or quercetin glycosides, 70 ppm of quercetin

and/or glycoside, especially between 50 and 100 ppm, and - at least 500 ppm of anthocyanidins, preferably at least 600 ppm, even more

preferably at least 700 ppm.

[0077] According to a first embodiment, a particularly suitable method is a method comprising the following steps: - obtaining an extract of Vitis vinifera:

a. extraction with water and/or ethanol of Vitis vinfera, preferably of all the leaves, fruits, skin, seeds and wood of Vitis vinifera. The amount of solvent

(30% v/v to 96% v/v) used is between 2 and 10 times the mass of material used. The extraction time can be between 30 minutes and 24 hours and the

extraction temperature between 20°C and 80°C. The raw materials used can be in dry, fresh or frozen form, whole or ground;

b. separation of the water and/or ethanol solution from the solid material, for example by centrifugal decantation or by pressing and filtration;

c. evaporation of ethanol by vacuum evaporation at a temperature preferably lower than 60°C and at a pressure lower than 100mbars; d. membrane separation of the previously desolvated extract so as to select preferentially the proanthocyanidic monomers and oligomers (having a degree of polymerization of between 2 and 10 inclusive) and to eliminate the flavanol polymers (> to decamers), in order to obtain an extract comprising at least 1% of catechins and/or epicatechins. This step can be carried out using a filtration membrane having a cut-off threshold of less than 15,000 daltons and more preferably less than 3,000 daltons ; - obtaining an extract of Vaccinium angustifolium: a. extraction with water and/or ethanol of Vaccinium angustifolium, preferably of all the leaves and fruits of Vaccinium angustifolium, The quantity of solvent (30% v/v to 96% v/v) used is between 2 and 10 times the mass of material used. The extraction time can be between 30 minutes and 24 hours and the extraction temperature between 20°C and 80°C. The raw materials used can be in dry, fresh or frozen form; b. separation of the water and/or ethanol solution from the solid matter by centrifugal decantation or by pressing and filtration; c. evaporation of ethanol by vacuum evaporation at a temperature preferably lower than 60°C and a pressure lower than 100 mbar; d. drying of extracts by atomization, vacuum oven or freeze-drying with or without a support such as maltodextrin; - mixture of Vitis vinifera and Vaccinium angustifolium extracts before or after the drying step.

[0078] According to a second embodiment, the method consists of implementing the following steps:

- mixture of Vitis vinifera and Vaccinium angustifolium, extraction with water and/or ethanol of Vaccinium angustifolium, preferably of all the leaves and fruits of

Vaccinium angustifolium, The quantity of solvent (30% v/v to 96% v/v) used is between 2 and 10 times the mass of material used. The extraction time can be

between 30 minutes and 24 hours and the extraction temperature between 20°C

and 80°C. The raw materials used can be in dry, fresh or frozen form; - separation of the water and/or ethanol solution from the solid marc by centrifugal

decantation or by pressing and filtration;

- evaporation of ethanol by vacuum evaporation at a temperature preferably lower

than 60°C and a pressure lower than 100 mbar; - drying of the extract by spraying or sublimation with or without a carrier such as

maltodextrin.

[0079] In any embodiment, prior to the drying step, the process may include the following steps: - loading of mixed or unmixed extract solutions on a resin,

- rinse the resin with water,

- application of a water/ethanol eluting solution on the resin,

- recovery of the purified eluate, - evaporation of ethanol from said eluate,

- concentration of said eluate - drying said purified aqueous extract.

[0080] The invention is now illustrated by non-limiting examples of compositions according to

the invention and by results.

[0081] Examples

[0082] Example 1: Nutritional composition for humans

[0083] Example 1 is a 400 mg capsule, consisting of: - Mixture of extracts: 300 mg

.0 - Mixture of 6 probiotics (Lactobacillus fermentum, L. plantarum, L. acidophilus,

Bfidobacterium lactis, B. Iongum, B. bifidum) 3x10A9 CFU: 50 mg - Maltodextrin: 50 mg.

The composition is obtained by mixing the constituents under the conventional condi

tions known to the man of the trade, and put in a capsule under the conventional con ditions also. The recommended dosage is 2 capsules per day.

[0084] Example 2: Nutritional composition for humans

[0085] Example 2 is a 3200 mg sachet, consisting of: - Mixture of extracts: 600 mg - Mixture of 3 probiotics (Lactobacillusacidophilus, Bifidobacterium bifidum, Lacto

bacillusfermentum) 4x10A9 CFU: 2500 mg - Maltodextrin: 100 mg.

tions known to the man of the trade and is presented in the form of a powder contained

in a sachet under the conventional conditions also. The recommended dosage is 1 sa chet per day.

[0086] Example 3: Nutritional composition for animals

[0087] Example 3 is a soft capsule consisting of: - Mixture of extracts: 50 mg - Mixture of 2 probiotics (Enterocossus faecium, Lactobacillus acidophilus casei)

3x10A9 CFU: 4167 mg

- FOS: 16610 mg The composition is obtained by mixing the constituents under conventional conditions

known to the man of the trade and is presented in the form of a soft capsule under

conventional conditions as well. The recommended dosage is 1 capsule per day.

[0088] Example 4: Nutritional composition for animals

[0089] Example 4 is a tablet consisting of: - Mixture of extracts: 50 mg - Mixture of 5 probiotics (Lactobacillusacidophilus, L. plantarum, L. Brevis, Bifidobac

terium animalis lactis, Lactobacillus ramnosus) 2x10A9 CFU :26.5 mg - FOS: 250 mg.

The composition is obtained by mixing the constituents under the conventional condi tions known to the man of the trade and is presented in the form of a tablet under the

conventional conditions also. The recommended dosage is 1 tablet per day for a dog of

10 kg.

Claims

Claims 1. Composition comprising:

- at least one mixture of extracts of Vitis vinifera and Vaccinium angustifolium, and

- at least one probiotic bacterium and/or probiotic yeast.
2. Composition according to the preceding claim, wherein the mixture of Vitis vinifera and Vaccinium angustifolium extracts comprises a mixture of molecules comprising:

- at least 1% of catechins and/or epicatechins, the percentage being given by

weight with respect to the total weight of the mixture, and

- at least 5 ppm ferulic acid, and/or

- at least 200 ppm resveratrol, and/or

- at least 50 ppm of quercetins and/or quercetin glycosides and/or

- at least 500 ppm of anthocyanins.
3. Composition according to any one of the preceding claims, wherein the probiotic bacteria

and/or yeast is selected from bacteria and/or yeasts of the genus Lactobacillus, Lactobacillus, Bifidobacterium, Bacillus, Streptococcus, Saccharomyces, Enterococcus, Clostridium,

Lactococcus and Escherichia.
4. Composition according to any one of the preceding claims, wherein the composition also comprises at least one prebiotic chosen from inulin, oligosaccharides, FOS, GOS, CLA

(conjugated linoleic acid), PUFA (polyunsaturated fatty acid), MOS (mannan-oligo-saccharide) and XOS (xylo-oligo-saccharide).
5. Composition according to any one of the preceding claims, wherein the composition is encapsulated or microencapsulated in a food carrier chosen from maltodextrin, gum arabic, hydrogenated or non-hydrogenated oil, wax alginates, starch, hydrolysed or non-hydrolysed

proteins, phosphatidylcholine, phospholipids, galactomannan, emulsifiers selected from pectin or polyglycerol polyricinoleate and fibres selected from polydextrose, HPMC and

cellulose.

CAF-100196AU-21102021